StemCell Therapy

Adult stem cells stored at a laboratory. A new treatment led to long-standing remission for MS patients. Photograph: MedicImage/Alamy

A radical and risky stem cell therapy has been shown to halt and even reverse some of the symptoms of those worst affected by multiple sclerosis, a disease that in many people has proved untreatable.

Doctors in Canada conducted an experimental stem cell transplant with 24 patients who were expected to be confined to a wheelchair within 10 years. After receiving the treatment most of the patients regained control of their lives, becoming able to walk, play sport and drive.

To succeed, the transplant required the destruction and rebooting of each persons immune system such a high risk approach that one of the patients died. But the others, followed up for between four and 13 years, had no further progression of the disease. The disease normally entails worsening symptoms over time.

To the surprise of their doctors, some patients recovered functions that had been eroded by the disease, including their sight and balance. Six returned to work or college, five married or became engaged and two had children using banked sperm or eggs, as the aggressive treatment had made them infertile.

Mark Freedman, a neurologist at the University of Ottawa, who co-led the trial, said he would not say his patients were cured. I hesitate to use the c-word. A cure would be stopping all disease moving forward and repairing all damage that has occurred. As far as we can ascertain no new damage seems to occur beyond the treatment and patients dont need to take any medication, so in that sense I think it has induced a long-standing remission. Some patients did recover substantial function and it allowed them to do things they couldnt do for years, but others did not.

However, the long-term results of the trial in Canada, published in the Lancet medical journal, have been universally applauded by scientists and support groups and will lead to a worldwide clamour for the transplants to be more widely available.

Stephen Minger, a stem cell biologist and independent consultant, said: The clinical results are truly impressive, in some cases close to being curative, though we need longer-term follow-up to know for certain whether the patients continue to do well or if there is a chance of relapse. And of course this trial will need replication by other groups too.

For a life-long progressive disease like MS with few treatment options this is really exciting data. It offers the hope of having a long-lasting treatment which may halt disease progression though, again, this is a very invasive therapy and not without risks. Still I would consider it a breakthrough therapy, and the clinical group and the patients should be congratulated for this success.

The doctors say this treatment is not for everyone with MS because of the dangers. Modern drugs can control the symptoms for most people with the disease, but they do not work in people who have a sudden onset of very aggressive disease with frequent relapses. Freedman said the transplants they had been doing in Ontario were suitable for perhaps 5-10% of MS patients. It is needless if the disease can be controlled with mild medicines that dont carry those kind of risks, he said.

Multiple sclerosis is caused by a malfunction of the immune system, which ordinarily defends the body against bacteria, viruses and disease. The disease attacks instead the insulating myelin sheath, which is essential for the proper functioning of the nervous system. Those who are badly affected, usually young, progressively lose the ability to control their limbs.

Stem cell transplants have been carried out before in MS patients, but those people had a relapse after a couple of years. Never before have doctors used the aggressive drug regimen used in Canada a therapy that totally destroys the immune system, putting patients at risk for a while from life-threatening infections.

The patient in the transplant group who died suffered very severe liver damage and a bacterial infection which caused sepsis, or blood poisoning.

In the process, the Canadian doctors removed stem cells from the bone marrow of the patients and processed these in a laboratory. They then used a combination of three toxic drugs to destroy each patients immune system before transplanting the cleaned-up stem cells in to the body.

There were some fairly profound and wonderful changes that some of them experienced, said Freedman. Some people hadnt walked and started walking. Some people who had lost their vision were seeing. More than half the patients returned to gainful employment, maintained their relationships, got back their drivers licence.

Some, however, had disease that was progressing like a runaway train, he said. They continued to get worse for a couple of years but then their disease also stopped progressing. But nobody developed any new inflammation at all, he said. Their brain scans showed no new lesions, he added.

People with MS have been going to clinics in Mexico and elsewhere in the world in search of stem cell treatments they hope will turn out to bring a cure. But doctors emphasised that the regimen used in Canada, being very dangerous, had to be restricted to very specialised centres, and needed to be tested in more people before it became more widely available.

In the UK, Paolo Muraro, a neurologist at Imperial College London, who met Freedman last week to discuss the results, is hoping to start his own international trial, involving about 180 people with MS. That trial would try a slightly less intense drug regime in the hope of reducing the risks, he said. He was still seeking funding for it and said the treatment might have been more widely available by now if it had been a drug.

Related: 'It was really the last option': one woman's multiple sclerosis recovery

The treatment does not rely on any proprietary drug, so it is not a treatment that has received any support from the pharmaceutical industry. People like Mark Freedman and myself have had to work with very limited resources to try to develop this treatment really from charitable funding and academia-driven units.

The Canadian results were indeed very good news, he said, although, he added, it was important to avoid raising false hopes, because of the risks and the need for more trials.

The study in Ontario was funded by the MS Society of Canada. Charities in the UK also welcomed the findings but warned that people with MS who might think of having a stem cell transplant should speak to their doctor.

Emma Gray, head of clinical trials at the MS Society, said: This treatment does offer hope, but its also an aggressive procedure that comes with substantial risks and requires specialist aftercare. If anyone is considering [a stem cell transplant] wed recommend they speak to their neurologist.

Amy Bowen, at the Multiple Sclerosis Trust, said the results were extremely interesting and encouraging. She added: Stem cell therapy is still very experimental, and is not suitable for everyone. However, it could be a potentially very effective therapy, holding great promise for people living with MS. Its also a long way from being a routine treatment for MS.

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Stem cell therapy gives hope to MS patients | Society ...

MS brain lesion as seen on an MRI.

By obliterating the broken immune systems of patients with severe forms of multiple sclerosis, then sowing fresh, defect-free systems with transplanted stem cells, researchers can thwart the degenerative autoimmune diseasebut it comes at a price.

In a small phase II trial of 24 MS patients, the treatment halted or reversed the disease in 70 percent of patients for three years after the transplant. Eight patients saw that improvement last for seven and a half years, researchers report in the Lancet. This means that some of those patients went from being wheelchair-bound to walking and being active again. But to reach that success, many suffered through severe side effects, such as life threatening infections and organ damage from toxicity brought on by the aggressive chemotherapy required to annihilate the bodys immune system. One patient died from complications of the treatment, which represents a four percent fatality rate.

Moreover, while the risks may be worthwhile to some patients with rapidly progressing forms of MSa small percentage of MS patientsthe researchers also caution that the trial was small and did not include a control group.

Larger clinical trials will be important to confirm these results, study coauthor Mark Freedman of University of Ottawa said in a statement. Since this is an aggressive treatment, the potential benefits should be weighed against the risks of serious complications associated with [this stem cell transplant], and this treatment should only be offered in specialist centres experienced both in multiple sclerosis treatment and stem cell therapy, or as part of a clinical trial, he added.

Similar treatments have been used before in other trials, which also showed positivethough not as dramaticresults. Generally, researchers start by harvesting a patients haematopoietic stem cells, which give rise to the bodys immune system. Then researchers use chemotherapy to knock back the patients misbehaving immune system. In MS patients, defective immune responses rip off the insulation from nerve cells in the brain and spinal cord, causing inflammation, lesions, and nerve damage that eventually lead to physical and mental disabilities. The disease can progress in bouts over decades or continuously over months.

With that defective immune system weakened, researchers can replace the patient's stem cells, which are distant enough predecessors that they don't carry the glitches that trigger MS. Thus, they can potentially spawn a flaw-free immune system.

Freedman and colleagues took this general treatment strategy a step further by not just knocking back the patients defective immune system, but byannihilating it completely with a cocktail of powerful drugs.

It's important to stress that this is a very early study, Stephen Minger, a stem cell biologist not involved with the study, told the BBC. Nevertheless, the clinical results are truly impressive, in some cases close to being curative.

Freedman added that future research will be geared not only to replicating the results in larger trials, but to figuring out how to make it safer for patients.

Lancet, 2016. DOI: 10.1016/S0140-6736(16)30169-6 (About DOIs).

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Risky stem cell treatment reverses MS in 70% of patients ...

Conference Series LLCinvites all the participants from all over the world to attend '8th World Congress on Cell & Stem Cell Research during March 20-22, 2017 in Orlando, USA which includes prompt keynote presentations, Oral talks, Poster presentations and Exhibitions.

Stem cellsare cells originate in all multi-cellular organisms. They were isolated in mice in 1981 and in humans in 1998. In humans there are several types of stem cells, each with variable levels of potency. Stem cell treatments are a type of cell therapy that introduces new cells into adult bodies for possible treatment of cancer, diabetes, neurological disorders and other medical conditions. Stem cells have been used to repair tissue damaged by disease or age.

Objective

Stem Cell Research-2017 has the platform to fulfill the prevailing gaps in the transformation of this science of hope, to serve promptly with solutions to all in the need. Stem Cell Research 2017 will have an anticipated participation of 120+ delegates across the world to discuss the conference goal.

Success Story: Cell Science Conference Series

The success of the Cell Science conference series has given us the prospect to bring the gathering inOrlando,USA. Since its commencement in 2011 Cell Science series has witnessed around 750 researchers of great potentials and outstanding research presentations from around the world. Awareness of stem cells and its application is becoming popular among the general population. Parallel offers of hope add woes to the researchers of cell science due to the potential limitations experienced in the real-time.

About Organizers

Conference Series LLCis one of the leadingOpen Access publishersand organizers of international scientificconferences and events every year across USA, Europe & Asia Conference Series LLChas so far organized 3000+Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on Medical, Pharma, Engineering, Science, Technology and Business with 700+ peer-reviewed open accessjournalsin basic science, health, and technology. OMICS International is also in association with more than 1000 International scientific and technological societies and associations and a team of 30,000 eminent scholars, reputed scientists as editorial board members.

Scientific Sessions

Stem Cell Research-2017 will encompass recent researches and findings in stem cell technologies, stem cell therapies and transplantations, current understanding of cell plasticity in cancer and other advancements in stem cell research and cell science.Stem Cell Research-2017 will be a great platform for research scientists and young researchers to share their current findings in this field of applied science. The major scientific sessions in Stem Cell Research-2017will focus on the latest and exciting innovations in prominent areas of cell science and stem cell research.

Target Audience:

Eminent personalities, Directors, CEO, President, Vice-president, Organizations, Associations heads and Professors, Research scientists, Stem Cell laboratory heads, Post-docs, Students other affiliates related to the area of Stem cell research, stem cell line companies can be as Target Audience.

8th World Congress on Cell & Stem Cell Research

The success of the 7 Cell Science conferences series has given us the prospect to bring the gathering one more time for our 8thWorld Congress 2017 meet in Orlando, USA. Since its commencement in 2011 cell science series has perceived around 750 researchers of great potentials and outstanding research presentations around the globe. The awareness of stem cells and its application is increasing among the general population that also in parallel offers hope and add woes to the researchers of cell science due to the potential limitations experienced in the real-time.

Stem Cell Research-2017has the goal to fill the prevailing gaps in the transformation of this science of hope to promptly serve solutions to all in the need.World Congress 2017 will have an anticipated participation of 100-120 delegates from around the world to discuss the conference goal.

History of Stem cells Research

Stem cells have an interesting history, in the mid-1800s it was revealed that cells were basically the building blocks of life and that some cells had the ability to produce other cells. Efforts were made to fertilize mammalian eggs outside of the human body and in the early 1900s, it was discovered that some cells had the capacity to generate blood cells. In 1968, the first bone marrow transplant was achieved successfully to treat two siblings with severe combined immunodeficiency. Other significant events in stem cell research include:

1978: Stem cells were discovered in human cord blood 1981: First in vitro stem cell line developed from mice 1988: Embryonic stem cell lines created from a hamster 1995: First embryonic stem cell line derived from a primate 1997: Cloned lamb from stem cells 1997: Leukaemia origin found as haematopoietic stem cell, indicating possible proof of cancer stem cells

Funding in USA:

No federal law forever did embargo stem cell research in the United States, but only placed restrictions on funding and use, under Congress's power to spend. By executive order on March 9, 2009, President Barack Obama removed certain restrictions on federal funding for research involving new lines of humanembryonic stem cells. Prior to President Obama's executive order, federal funding was limited to non-embryonic stem cell research and embryonic stem cell research based uponembryonic stem celllines in existence prior to August 9, 2001. In 2011, a United States District Court "threw out a lawsuit that challenged the use of federal funds for embryonic stem cell research.

Members Associated with Stem Cell Research:

Discussion on Development, Regeneration, and Stem Cell Biology takes an interdisciplinary approach to understanding the fundamental question of how a single cell, the fertilized egg, ultimately produces a complex fully patterned adult organism, as well as the intimately related question of how adult structures regenerate. Stem cells play critical roles both during embryonic development and in later renewal and repair. More than 65 faculties in Philadelphia from both basic science and clinical departments in the Division of Biological Sciences belong to Development, Regeneration, and Stem Cell Biology. Their research uses traditional model species including nematode worms, fruit-flies, Arabidopsis, zebrafish, amphibians, chick and mouse as well as non-traditional model systems such as lampreys and cephalopods. Areas of research focus include stem cell biology, regeneration, developmental genetics, and cellular basis of development, developmental neurobiology, and evo-devo (Evolutionary developmental biology).

Stem Cell Market Value:

Worldwide many companies are developing and marketing specialized cell culture media, cell separation products, instruments and other reagents for life sciences research. We are providing a unique platform for the discussions between academia and business.

Global Tissue Engineering & Cell Therapy Market, By Region, 2009 2018

$Million

Why to attend???

Stem Cell Research-2017 could be an outstanding event that brings along a novel and International mixture of researchers, doctors, leading universities and stem cell analysis establishments creating the conference an ideal platform to share knowledge, adoptive collaborations across trade and world, and assess rising technologies across the world. World-renowned speakers, the most recent techniques, tactics, and the newest updates in cell science fields are assurances of this conference.

A Unique Opportunity for Advertisers and Sponsors at this International event:

http://stemcell.omicsgroup.com/sponsors.php

UAS Major Universities which deals with Stem Cell Research

University of Washington/Hutchinson Cancer Center

Oregon Stem Cell Center

University of California Davis

University of California San Francisco

University of California Berkeley

Stanford University

Mayo Clinic

Major Stem Cell Organization Worldwide:

Norwegian Center for Stem Cell Research

France I-stem

Stem Cell & Regenerative Medicine Ctr, Beijing

Stem Cell Research Centre, Korea

NSW Stem Cell Network

Monash University of Stem Cell Labs

Australian Stem Cell Centre

Target Audience:

Eminent personalities, Directors, CEO, President, Vice-president, Organizations, Associations heads and Professors, Research scientists, Stem Cell laboratory heads, Post-docs, Students other affiliates related to the area of Stem cell research, stem cell line companies can be as Target Audience

Market Analysis of Stem Cell Therapy:

The global market for stem cell products was $3.8 billion in 2011. This market is expected to reach nearly $4.3 billion in 2012 and $6.6 billion by 2016, increasing at a compound annual growth rate (CAGR) of 11.7% from 2011 to 2016.

Americas is the largest region of global stem cell market, with a market share of about $2.0 billion in 2013. The region is projected to increase to nearly $3.9 billion by 2018, with a CAGR of 13.9% for the period of 2013 to 2018

Europe is the second largest segment of the global stem cell market and is expected to grow at a CAGR of 13.4% reaching about $2.4 billion by 2018 from nearly $1.4 billion in 2013.

Figure 2:Global Market

Companies working for Stem Cells:

Company

Location

Business Type

Cynata Therapeutics

Armadale, Australia

Stem Cell Manufacturing Technology

Mesoblast

Melbourne, Australia

Regenerative Medicine

Activartis

Vienna, Austria

Dendritic Cell-Based Cancer Immunotherapy

Aposcience

Vienna, Austria

Treatments composed of mixture of cytokines, growth factors and other active components

Cardio3 Biosciences

Mont-Saint-Guibert, Belgium

Stem Cell Differentiation

Orthocyte (BioTime)

Alameda, CA

Cellular Therapies

Capricor

Beverly Hills, CA

Stem Cell Heart Treatments

Life Stem Genetics

Beverly Hills, CA

Autologous stem cell therapy

International Stem Cell

Carlsbad, CA

Proprietary Stem Cell Induction

Targazyme

Carlsbad, CA

Cell Therapy

DaVinci Biosciences

Costa Mesa, CA

Cellular Therapies

Invitrx Therapeutics

Irvine, CA

Autologous Stem Cell Therapy, Therapeutic & Cosmetic

Stem Cell Softwares :

Products Manufactured By Industry Related to Stem Cell:

Original post:
Worlds leading Stem Cell Conference | Global Meetings ...

Int J Biomater. 2012; 2012: 926059.

1Department of Surgery, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA

2Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Stanford University, 257 Campus Drive, Stanford, CA 94305, USA

3Department of Surgery, Plastic and Reconstructive Surgery Division, Division of Burn Surgery, University of Michigan Health Systems, 1500 East Medical Center Drive, Ann Arbor, MI 48104, USA

4The Biomaterials and Advanced Drug Delivery (BioADD) Laboratory, Stanford University, 300 Pasteur Drive, Grant Building, Room S380, Stanford, CA 94305, USA

Academic Editor: Kadriye Tuzlakoglu

Received 2012 Jan 15; Accepted 2012 Apr 8.

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Stem cell-based therapies offer tremendous potential for skin regeneration following injury and disease. Functional stem cell units have been described throughout all layers of human skin and the collective physical and chemical microenvironmental cues that enable this regenerative potential are known as the stem cell niche. Stem cells in the hair follicle bulge, interfollicular epidermis, dermal papillae, and perivascular space have been closely investigated as model systems for niche-driven regeneration. These studies suggest that stem cell strategies for skin engineering must consider the intricate molecular and biologic features of these niches. Innovative biomaterial systems that successfully recapitulate these microenvironments will facilitate progenitor cell-mediated skin repair and regeneration.

Skin serves as the interface with the external world and maintains key homeostatic functions throughout life. This regenerative process is often overlooked until a significant exogenous and/or physiologic insult disrupts our ability to maintain skin homeostasis [1]. Complications of normal repair often result in chronic wounds, excessive scarring, or even malignant transformation, cutaneous diseases that contribute substantially to the global health burden [2, 3]. As human populations prone to inadequate healing (such as the aged, obese, and diabetics) continue to expand, novel therapies to treat dysfunctional skin repair and regeneration will become more critical.

Tissue regeneration has been demonstrated in multiple invertebrate and vertebrate species [4]. In humans, even complex tissues can regenerate without any permanent sequelae, such as liver, nerves, and skin. Although the typical result after significant organ injury is the formation of scar, regeneration after extensive skin and soft tissue trauma has been reported, most notably after digit tip amputation [5]. It is well accepted that human skin maintains the ability to regenerate; the question for researchers and clinicians is how to harness this potential to treat cutaneous injury and disease.

The integumentary system is a highly complex and dynamic system composed of myriad cell types and matrix components. Numerous stem cell populations have been identified in skin and current research indicates that these cells play a vital role in skin development, repair, and homeostasis [1, 6, 7]. In general, stem cells are defined by their ability to self-renew and their capacity to differentiate into function-specific daughter cells. These progenitor cells have been isolated from all skin layers (epidermis, dermis, hypodermis) and have unique yet complimentary roles in maintaining skin integrity. The promise of regenerative medicine lies in the ability to understand and regulate these stem cell populations to promote skin regeneration [4].

Wound healing is a highly regulated process that is thought to be mediated in part by stem cells [8, 9]. This has prompted researchers to examine the use of stem cells to augment skin repair following injury. Preclinical studies have suggested that the secretion of paracrine factors is the major mechanism by which stem cells enhance repair [10, 11]. Consistent with this hypothesis, conditioned media from mesenchymal stem cells (MSCs) have been shown to promote wound healing via activation of host cells [11, 12]. Clinical studies have suggested that topical delivery of MSCs may improve chronic wound healing [1315] and multiple groups have demonstrated the benefit of using recombinant cytokines (many of which are known to be secreted by stem cells) in patients with recalcitrant wounds [16]. However, more research is needed to determine the mechanisms by which stem cell therapies might improve wound healing in humans.

For example, the extent of stem cell engraftment and differentiation following topical delivery remains unclear. In one study, bone-marrow-derived allogeneic MSCs injected into cutaneous wounds in mice were shown to express keratinocyte-specific proteins and contributed to the formation of glandular structures after injury [17]. Although long-term engraftment was poor (only 2.5% of MSCs remained engrafted after four weeks), levels of secreted proangiogenic factors were greater in MSC-treated wounds. Our laboratory has demonstrated that local injection of allogeneic MSCs improved early wound closure in mice but that injected MSCs contributed to less than 1% of total wound cells after four weeks [18]. Taken together, these studies suggest that the benefits observed with stem cell injections are the result of early cytokine release rather than long-term engraftment and differentiation.

One potential reason for the transient presence of exogenous stem cells is the absence of proper contextual cues after cells are delivered into the wound. The dynamic microenvironment, or niche, of stem cells is responsible for regulating their stem-like behavior throughout life [19, 20]. This niche is comprised of adjacent cells (stem and nonstem cells), signaling molecules, matrix architecture, physical forces, oxygen tension, and other environmental factors (). A useful analogy is the seed versus soil paradigm in which seeds (stem cells) will only thrive in the proper chemical and physical soil environment (wound bed) [4]. Clearly, we need to better define what these niches are and how they dictate cell behavior to fully realize the potential of progenitor cell therapies.

Potential components of the skin stem cell niche. Features common to skin stem cell niches include dynamic regulation of matrix ligands, intercellular interactions, and biochemical gradients in the appropriate three-dimensional contexts. Engineered biomaterials ...

The epidermis is comprised of at least three major stem cell populations: the hair follicle bulge, the sebaceous gland, and the basal layer of interfollicular epithelium [21]. Because these subpopulations are responsible for regulating epithelial stratification, hair folliculogenesis, and wound repair throughout life [22], the epidermis has become a model system to study regeneration. Elegant lineage tracing and gene mapping experiments have elucidated key programs in epidermal homeostasis. Specifically, components of the wingless-type (Wnt)/-catenin, sonic hedgehog (Shh), and transforming growth factor (TGF)-/bone morphogenetic protein (BMP) pathways appear to be particularly relevant to epidermal stem cell function [1, 22, 23]. Microarray analyses have even indicated that hair follicle stem cells share some of the same transcriptomes as other tissue-specific stem cells [24], suggesting that conserved molecular machinery may control how environmental stimuli regulate the stem cell niche [25].

Epithelial stem cells from the bulge, sebaceous gland, and basal epithelium have common features, including expression of K5, K14, and p63, and their intimate association with an underlying basement membrane (BM) [26]. These cells reside in the basal layer of stratified epithelium and exit their niche during differentiation [26]. This process is mediated in part by BM components such as laminin and cell surface transmembrane integrins that control cell polarity, anchorage, proliferation, survival, and motility [27, 28]. Epithelial progenitor cells are also characterized by elevated expression of E-cadherin in adherens junctions and reduced levels of desmosomes [29], underscoring the importance of both extracellular and intercellular cues in stem cell biology.

In addition to complex intraepithelial networks, signals from the dermis (e.g., periodic expression of BMP2 and BMP4) are thought to regulate epithelial processes [30]. Dermal-derived stem cells may even differentiate into functional epidermal melanocytes [31], suggesting that mesenchymal-epithelial transitions may underlie skin homeostasis, as has been shown in hepatic stem cells [32]. Recently, it has been demonstrated that irreversibly committed progeny from an epithelial stem cell lineage may be recycled and contribute back to the regenerative niche [33], further highlighting the complexity of the epidermal regeneration.

In contrast to the highly cellular nature of the epidermis, the dermis is composed of a heterogeneous matrix of collagens, elastins, and glycosaminoglycans interspersed with cells of various embryonic origin. Recent studies suggest that a cell population within the dermal papilla of hair follicles may function as adult dermal stem cells. This dermal unit contains at least three unique populations of progenitor cells differentiated by the type of hair follicle produced and the expression of the transcription factor Sox2 [34]. Sox2-expressing cells are associated with Wnt, BMP, and fibroblast growth factor (FGF) signaling whereas Sox2-negative cells utilize Shh, insulin growth factor (IGF), Notch, and integrin pathways [35, 36]. Skin-derived precursor (SKP) cells have also been isolated from dermal papillae and can be differentiated into adipocytes, smooth myocytes, and neurons in vitro [37, 38]. These cells are thought to originate in part from the neural crest and have been shown to exit the dermal papilla niche and contribute to cutaneous repair [39].

Researchers have also demonstrated that perivascular sites in the dermis may act as an MSC-like niche in human scalp skin [40]. These perivascular cells express both NG2 (a pericyte marker) and CD34 (an MSC and hematopoietic stem cell marker) and are predominantly located around hair follicles. Perivascular MSC-like cells have been shown to protect their local matrix microenvironment via tissue-inhibitor-of-metalloproteinase (TIMP-) mediated inhibition of matrix metalloproteinase (MMP) pathways, suggesting the importance of the extracellular matrix (ECM) niche in stem cell function [41]. Interestingly, even fibroblasts have been shown to maintain multilineage potential in vitro and may play important roles in skin regeneration that have yet to be discovered [42, 43].

The ability to harvest progenitor cells from adipose tissues is highly appealing due to its relative availability (obesity epidemic in the developed world) and ease of harvest (lipoaspiration). Secreted cytokines from adipose-derived stem cells (ASCs) have been shown to promote fibroblast migration during wound healing and to upregulate VEGF-related neovascularization in animal models [44]. ASCs have even been harvested from human burn wounds and shown to engraft into cutaneous wounds in a rat model [45]. Although these multipotent cells have only been relatively recently identified, they exhibit significant potential for numerous applications in skin repair [46].

ASCs are often isolated from the stromal vascular fraction (SVF) of homogenized fat tissue. These multipotent cells are closely associated with perivascular cells and maintain the potential to differentiate into smooth muscle, endothelium, adipose tissue, cartilage, and bone [47, 48]. Researchers have attempted to recreate the ASC niche using fibrin matrix organ culture systems to sustain adipose tissue [49]. Using this in vitro system, multipotent stem cells were isolated from the interstitium between adipocytes and endothelium, consistent with the current hypothesis that ASCs derive from a perivascular niche.

Detailed immunohistological studies have demonstrated that stem cell markers (e.g., STRO-1, Wnt5a, SSEA1) are differentially expressed in capillaries, arterioles, and arteries within adipose tissue, suggesting that ASCs may actually be vascular stem cells at diverse stages of differentiation [50]. Adipogenic and angiogenic pathways appear to be concomitantly regulated and adipocytes secrete multiple cytokines that induce blood vessel formation including vascular endothelial-derived growth factor (VEGF), FGF2, BMP2, and MMPs [51, 52]. Additionally, cell surface expression of platelet-derived growth factor receptor (PDGFR) has been linked to these putative mural stem cells [53]. Reciprocal crosstalk between endothelial cells and ASCs may regulate blood vessel formation [54] and immature adipocytes have been shown to control hair follicle stem cell activity through PDGF signaling [55]. Taken together, these studies indicate that the ASC niche is intimately associated with follicular and vascular homeostasis but further studies are needed to precisely define its role in skin homeostasis [48].

Strategies to recapitulate the complex microenvironments of stem cells are essential to maximize their therapeutic potential. Biomaterial-based approaches can precisely regulate the spatial and temporal cues that define a functional niche [56]. Sophisticated fabrication and bioengineering techniques have allowed researchers to generate complex three-dimensional environments to regulate stem cell fate. As the physicochemical gradients, matrix components, and surrounding cells constituting stem cell niches in skin are further elucidated (), tissue engineered systems will need to be increasingly scalable, tunable, and modifiable to mimic these dynamic microenvironments [5761]. A detailed discussion of different biomaterial techniques for tissue engineering is beyond the scope of this paper, but we refer to reader to several excellent papers on the topic [6270].

Skin-specific stem cells and putative features of their niche.

One matrix component thought to regulate interactions between hair follicle stem cells and melanocyte stem cells is the hemidesmosomal collagen XVII [71]. Collagen XVII controls their physical interactions and maintains the self-renewal capacity of hair follicles via TGF-, indicating that biomaterial scaffolds containing collagen XVII may be necessary for stem cell-mediated hair follicle therapies. Another matrix component implicated in the hair follicle niche is nephronectin, a protein deposited into the underlying basement membrane by bulge stem cells to regulate cell adhesion via 81 integrins [72]. Hyaluronic acid fibers have been incorporated into collagen hydrogels to promote epidermal organization following keratinocyte seeding [73], and in vitro studies have demonstrated the critical role of collagen IV in promoting normal epithelial architecture when keratinocytes are grown on fibroblast-populated dermal matrices [74]. These studies collectively suggest that tissue engineered matrices for skin regeneration will need to recapitulate the complex BM-ECM interactions that define niche biology [75].

The role of MSCs in engineering skin equivalents has been studied using either cell-based or collagen-based dermal equivalents as the scaffolding environment [76]. When these constructs were grown with keratinocytes in vitro, only the collagen-based MSCs promoted normal epidermal and dermal structure, leading the authors to emphasize the necessity of an instructive biomaterial-based scaffold to direct stem cell differentiation, proliferation, paracrine activity [and] ECM deposition [76]. Our laboratory has reported that MSCs seeded into dermal-patterned hydrogels maintain greater expression of the stem cell transcription factors Oct4, Sox2, and Klf4 as compared to those grown on two-dimensional surfaces [18]. MSCs seeded into these niche-like scaffolds also exhibited superior angiogenic properties compared to injected cells [18], indicating that stem cell efficacy may be enhanced with biomaterial strategies to recapitulate the niche. Another study demonstrated that ASC delivery in natural-based scaffolds (dermis or small intestine submucosa) resulted in improved wound healing compared to gelatin-based scaffolds, suggesting the importance of biologically accurate architecture for stem cell delivery [77].

Researchers have developed novel three-dimensional microfluidic devices to study perivascular stem cell niches in vitro [78]. For example, MSCs seeded with endothelial cells in fibrin gels were able to induce neovessel formation within microfluidic chambers through 61 integrin and laminin-based interactions. Fibrin-based gels have also been used to study ASC and endothelial cell interactions in organ culture [49] and to control ASC differentiation in the absence of exogenous growth factors, demonstrating the importance of the three-dimensional matrix environment in regulating the ASC niche [79]. These studies indicate that the therapeutic use of ASCs in skin repair will likely be enhanced with biomaterial systems that optimize these cell-cell and cell-matrix contacts.

Finally, it must be recognized that the wound environment is exceedingly harsh and often characterized by inflammation, high bacterial loads, disrupted matrix, and/or poor vascularity. In this context, it should not be surprising that injection of naked stem cells into this toxic environment does not produce durable therapeutic benefits. Our laboratory has shown that the high oxidative stress conditions of ischemic wounds can be attenuated with oxygen radical-quenching biomaterial scaffolds that also deliver stem cells [80]. Other researchers have shown that oxygen tension, pH levels, and even wound electric fields may influence stem cell biology, suggesting that the future development of novel sensor devices will allow even finer control of chemical microgradients within engineered niches [70, 81]. It is also important to acknowledge that current research on niche biology has been performed largely in culture systems or rodent models, findings that will need to be rigorously confirmed in human tissues before clinical use.

As interdisciplinary fields such as material science, computer modeling, molecular biology, chemical engineering, and nanotechnology coordinate their efforts, multifaceted biomaterials will undoubtedly be able to better replicate tissue-specific niche environments. Recent studies suggest that the cells necessary for skin regeneration are locally derived [5], indicating that adult resident cells alone may have the ability to recreate skin (). Thus, the ability to engineer the proper environment for skin stem cells truly has the potential to enable regenerative outcomes. We believe that next-generation biomaterial scaffolds will not only passively deliver stem cells but also must actively modify the physicochemical milieu to create a therapeutic niche.

Locally derived skin stem cells may harbor the potential to regenerate skin. Stem cells populations have been identified in various niches throughout the skin, including the epidermal stem cell in the hair follicle bulge, sebaceous glands, and interfollicular ...

Current research indicates that skin regeneration is highly dependent upon interactions between resident progenitor cells and their niche. These microenvironmental cues dictate stem cell function in both health and disease states. Early progress has been made in elucidating skin compartment-specific niches but a detailed understanding of their molecular and structural biology remains incomplete. Biomaterials will continue to play a central role in regenerative medicine by providing the framework upon which to reconstruct functional niches. Future challenges include the characterization and recapitulation of these dynamic environments using engineered constructs to maximize the therapeutic potential of stem cells.

Articles from International Journal of Biomaterials are provided here courtesy of Hindawi Publishing Corporation

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Stem Cell Niches for Skin Regeneration

Stem Cell Technology represents a major breakthrough in anti-aging and regenerative skin care, by protecting, strengthening, and replenishing our own human skin cells. Where Peptides stimulate different functions acting as messengers to skin cells, stem cell technology improves the life of the core of the cell. Working in synergy with peptides, they enhance the effectiveness of peptides and other active ingredients.

Antiaging effects - The stem cells in our skin have a limited life expectancy due to DNA damage, aging and oxidative stress. As our own skin stem cells age, they become more difficult to repair and replenish. Protection of our stem cells becomes more and more beneficial as our skin ages, and with the advent of stem cells, we are now able to delay the natural aging process even further than before.

Expected benefits of stem cells technology for regenerative skin care:

Stem Cell Replenishing Serum Featuring a potent concentration of apple and edelweiss plant stem cells, state-of-the-art peptides, and other cutting edge ingredients, the Stem Cell Replenishing Serum is thoroughly formulated to produce age defying results, restoring the youthful look and vitality to aging skin.

Stem Cell Moisturizing Cream Also featuring a healthy concentration of apple and edelweiss plant stem cells, peptides, and numerous botanical extracts, the Stem Cell Moisturizing Cream is formulated to produce age defying results while also helping to maintain healthy and youthful looking skin as a daily moisturizer.

Our Stem Cell Applications:

LPAR Stem Cell Products contain a wide variety of stem cells with healthy and potent concentrations in order to deliver the results skin care consumers strive for. The first stem cell ingredient discovered and produced is a liposomal preparation based on the stem cells of a rare Swiss apple. The revolutionary active ingredient, Malus Domestica by PhytoCellTec is based on a high tech plant cell culture technology. It has been proven to protect the longevity of skin stem cells and provide significant anti-wrinkle effects. Since the discovery and the worldwide success of Apple Stem Cells introduction to the cosmetic and skin care marketplace, other new and exciting stem cell ingredients have been discovered to provide extraordinary results for all skin types.

We were proud to be the first skin care line to offer the ground-breaking combination of Apple and Edelweiss stem cells, and are dedicated to formulating the best new and existing stem cell ingredients into our product line as the technology continues to develop.

To inquire about purchasing LPAR Stem Cell products. visit our Retail Locator page.

Featuring a luxurious and potent blend of three major botanical stem cells (Apple, Gardenia Jasminoides, Echinacea Angustifolia) two state-of-the-art peptides (Nutripeptides, Matrixyl synthe6), and numerous botanical extracts and minerals, the Stem Cell Nourishing Mask is thoroughly formulated to nourish, firm, and energize mature skin. Total Stem Cell Concentration: 5.5% - Total Peptide Concentration: 9.0%

Directions: Using fingertips, apply on clean, dry skin twice weekly. Avoid the eye area. The mask can be left on the skin for prolonged periods (during the day or overnight). Allow at least 10-15 minutes for the mask to penetrate the skin before rinsing with water or applying additional product For external use only.

Ingredients: Water (Aqua), Glycerin, Glyceryl Acrylate/Acrylic Acid Copolymer, Hydrolyzed Rice Protein (Nutripeptides), Sodium Hyaluronate, Hydroxypropyl Cyclodextrin, Palmitoyl Tripeptide-38 (Matrixyl synthe6), Biosaccharide Gum-1, Olea Europaea (Olive) Fruit Oil, Gardenia Jasminoides Meristem Cell Culture, Xanthan Gum, Malus Domestica Fruit Cell Culture, Lecithin, Porphyridium Polysaccharide, Echinacea Angustifolia Meristem Cell Culture, Carbomer, Triethanolamine, Mentha Pipertita (Peppermint) Extract, Camellia Sinensis (Green Tea) Leaf Extract, Palmaria Palmata (Dulce) Extract, Chamomilla Recutita (Matricaria) Flower Extract, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Copper PCA, Zinc PCA, Dipotassium Glycyrrhizate, Olea Europaea (Olive) Fruit Extract, Aloe Barbadensis Leaf Juice Powder, Fragrance (Parfum)

Featuring a plant and fruit stem cell enhanced blend of three major stem cells (Apple, Edelweiss, Alpine Rose), state-of-the-art peptides (Eyeseryl, Nutripeptides), the Stem Cell Eye Therapy is an advanced eye formula designed to nourish, firm, and increase skin elasticity and skin smoothness around the eye area. Total Stem Cell Concentration: 6.75% - Total Peptide Concentration: 11.0%

Directions: Using fingertips, apply product around both eyes on clean, dry skin once or twice daily before applying a moisturizer or night cream. For external use only.

Ingredients: Water, Acetyl Tetrapeptide-5 (Eyeseryl), Sodium Hyaluronate, Hydrolyzed Rice Protein (Nutripeptides), Glycerin, Leontopodium Alpinum Meristem Cell Culture (Edelweiss Stem Cells), Xanthan Gum, Malus Domestica Fruit Cell Culture (Apple Stem Cells), Lecithin, Porphyridium Polysaccharide, Camellia Sinensis (Green Tea) Leaf Extract, Cucumis Sativus (Cucumber) Fruit Extract, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Carbomer, Triethanolamine, Rhododendron Ferrugineum Leaf Cell Culture Extract (Alpine Rose Stem Cells) Isomalt, Sodium Benzoate, Lactic Acid, Sodium Polystyrene Sulfonate, Allantoin, Copper PCA, Aloe Barbadensis Leaf Juice Powder

Plant stem cells represent a major breakthrough in skin care, launching the beginning of a new system of treating the skin...by protecting and replenishing the building blocks of what makes up our own skin: Stem Cells. Rather than working around the natural aging process of our skin stem cells, we now have the technology available to improve the life of our skins most important and central component.

Featuring a potent combination of apple, edelweiss, and grape stem cells, state-of-the-art peptides, and other cutting edge ingredients, the Stem Cell Replenishing Serum is thoroughly formulated to produce age defying results, restoring the youthful look and vitality to aging skin.

Directions: Apply with fingertips on clean, dry skin once or twice daily. Avoid the eye area by approximately 1 cm. Suitable for mature skin types. For external use only.

Ingredients: Water (Aqua), Glycerin, Dipeptide Diaminobutyroyl Benzylamide Diacetate, Acetyl Octapeptide-3, Malus Domestica Fruit Cell Culture (Apple Stem Cells), Hydrolyzed Ceratonia Siliqua Seed Extract, Palmitoyl Tripeptide-5, PEG-8 Dimethicone, Saccharide Isomerate, Imperata Cylindrica (Root) Extract, Polysorbate 20, Leontopodium Alpinum Meristem Cell Culture (Edelweiss Stem Cells), Leucojum Aestivum Bulb Extract, Triethanolamine, Carbomer, Xanthan Gum, Vitis Vinifera Fruit Cell Extract (Grape Stem Cells), Isomalt, Sodium Benzoate, Lecithin, Disodium EDTA, Allantoin, Aloe Barbadensis Leaf Juice Powder, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, PEG-8-Carbomer, Fragrance (Parfum)

Plant stem cells represent a major breakthrough in skin care, launching the beginning of a new system of treating the skin...by protecting and replenishing the building blocks of what makes up our own skin: Stem Cells. Rather than working around the natural aging process of our skin stem cells, we now have the technology available to improve the life of our skins most important and central component.

Featuring a healthy concentration and a diverse group of stem cells (apple, edelweiss, grape), peptides, and numerous botanical extracts, the Stem Cell Moisturizing Cream is formulated to produce age-defying results, while also helping to maintain healthy and youthful looking skin as a daily moisturizer.

Directions: For mature skin and/or skin conditioning, apply onto clean, dry skin with fingertips once daily. Avoid the eye. For external use only.

Ingredient Highlights: Plant/Fruit Stem Cells 4% - Malus Domestica (Apple Stem Cells) - Leontopodium Alpinum Cell Culture Extract (Edelweiss Stem Cells) - Vitis Vinifera Fruit Cell Extract (Grape Stem Cells)

Ingredients: Water (Aqua), Glycerin, Isopropyl Myristate, Caprylic/Capric Triglyceride, Cetearyl Olivate, Sorbitan Olivate, Sorbitol, Saccharide Isomerate, Sodium Hyaluronate, Leucojum Aestivum Bulb Extract, Malus Domestica Fruit Cell Extract (Apple Stem Cells), Leontopodium Alpinum Meristem Cell Culture (Edelweiss Stem Cells), Vitis Vinifera Fruit Cell Extract (Grape Stem Cells), Crambe Abyssinica Seed Oil, Dimethicone, Cetyl Alcohol, Imperata Cylindrica (Root) Extract, Acetyl Octapeptide-3 (SNAP-8), Dipeptide Diaminobutyroyl Benzylamide Diacetate(SYN-AKE), Palmitoyl Tripeptide-3 (SYN-COL), Hydrolyzed Ceratonia Siliqua Seed Extract, Aloe Barbadensis Leaf Juice Powder, Olea Europaea (Olive) Leaf Extract, Glyceryl Stearate, Xantham Gum, Cetyl Palmitate, Sorbitan Palmitate, Bisabolol, Tocopheryl Acetate, Fragrance, Phenoxyethanol, Caprylyl Glycol, Ethylhexyglycerin, Hexylene Glycol, PEG-8, Carbomer, Lecithin, Isomalt, Sodium Benzoate, Disodium EDTA

[ pH: 5.00 ]

Featuring high concentrations of Vitamin C (Tetrahexyldecyl Ascorbate), Orange Stem Cells, and Peptides, this is a multi-beneficial cream with state-of-the-art actives formulated to deliver significant and lasting results.

Tetrahexyldecyl Ascorbate is a stable, oil soluble form of Vitamin C that penetrates deeper into the skin than traditional ascorbic acid based Vitamin C. It's a proven skin lightener, a powerful Anti-Oxidant, DNA protector, and increases collagen synthesis more effectively than ascorbic acid. Orange Stem Cells work to increase elasticity and skin resistance to the dermis, which increase firmness and diminish wrinkles while also working synergistically with peptides to further increase skin elasticity and collagen support.

How to Use: Smooth a pearl sized drop onto the face once daily (morning or evening). Avoid the eye area while applying. Follow with Solar Protection if used during the day.

Ingredients: Water (Aqua), Tetrahexyldecyl Ascorbate (Vitamin C Ester), Glycerin, Hexyl Laurate, Caprylic/Capric Triglyceride, Butylene Glycol, Sorbitol, Stearic Acid, Glyceryl Stearate, PEG-100 Stearate, Cetyl Alcohol, Sorbitan Stearate, Polysorbate 60, Acetyl Hexapeptide-8, Sodium Hyaluronate, Squalane, Dimethicone, PPG-12/SMDI Copolymer, Citrus Aurantium Dulcis Callus Culture Extract (Orange Stem Cells), Tocopheryl Acetate, Cetearyl Ethylhexanoate, Linoleic Acid, Glycine Soja (Soybean) Sterols, Phospholipids, Di-PPG-2 Myreth-10 Adipate, Retinol, Polysorbate 20, Hydrolyzed Glycosaminoglycans, Alcohol, Ectoin, Lecithin, Cyclotetrapeptide-24 Aminocyclohexane Carboxylate, Glucosamine HCl, Algae Extract, Yeast Extract, Urea, Micrococcus Lysate, Plankton Extract, Arabidopsis Thaliana Extract, Magnesium Aluminum Silicate, Xanthan Gum, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Disodium EDTA, Citrus Aurantium Dulcis (Orange) Peel Oil

[ pH: 4.7 ]

The Vitamin C Stem Cell Mask combines a potent blend of Vitamin C Ester (Tetrahexyldecyl Ascorbate), highly concentrated plant and fruit stem cells (Argan, Sea Fennel), and Aldenine, a unique peptide that acts as a cellular detoxifier and a collagen III booster.

Directions: Apply on clean, dry skin. Avoid the eye area. The mask may be left on the skin (i.e. during the day or overnight), or it may be rinsed off with lukewarm water after 10 - 15 minutes. Suitable for mature skin types.

Ingredients: Water (Aqua), Tetrahexyldecyl Ascorbate, Kaolin, Glycerin, Glyceryl Stearate, Sorbitan Olivate, Cetearyl Olivate, Cetyl Palmitate, Sorbitol, Sorbitan Palmitate, Stearic Acid, Caprylic/Capric Triglyceride, Cyclopentasiloxane, Cyclhexasiloxane, Carthamus Tinctorius (Safflower) Seed Oil, Punica Granatum Extract, Butylene Glycol, Ananas Sativus (Pineapple) Fruit Extract, Carica Papaya Fruit Extract, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-1, Argania Spinosa (Argan Stem Cells) Sprout Cell Extract, Crithmum Maritimum (Sea Fennel Stem Cells) Callus Culture Filtrate, Oligopeptide-68, Sodium Oleate, Phenoxyethanol, Caprylyl Glycol, Ethylhexylglycerin, Hexylene Glycol, Polyacrylamide, C13-14 Isoparaffin, Laureth-7, Isomalt, Hydrogenated Lecithin, Lecithin, Sodium Benzoate, Allantoin, Citrus Aurantium Dulcis (Orange) Peel Oil, Magnesium Aluminum Silicate, Xanthan Gum, Disodium EDTA

[ pH: 6.00 ]

Originally designed to prepare and increase the skins receptiveness to our Professional Peptide Peel, the Premier Peptide Serum has gone on to become our most powerful anti-wrinkle product for year-round home care due to its high concentration and diversity of peptides. Composed of a total concentration of 65% peptides, the Premier Peptide Serum is a state of the art facial serum expertly formulated to reduce the signs of aging, energizing mature skin.

The Intensive Clarifying Peptide Cream is a unique and high potency moisturizing cream formulated with an abundance of natural skin lighteners, peptides, and botanical extracts that combine to clarify and firm mature skin, while effectively minimizing fine lines and wrinkles.

The Collagen Peptide Complex builds off of our original Collagen Copper Activating Complex, and includes an advanced formulation of peptides, including Syn-Coll, a small but powerful peptide that stimulates collagen synthesis at a cellular level, helping to compensate for any collagen deficit in the skin.

Boasting a remarkable collection of natural and innovative ingredients from exotic plants and enhanced peptides, the neck firming cream has been designed & tested to firm and energize mature skin, while providing increased smoothness and elasticity to the often neglected neck area.

Providing sufficient hydration is the most essential way to keep our skin healthy and youthful. While many of our products assist in hydrating the skin, hydration is the main focus of the Nano-Peptide B5 Complex, acting as the foundation for your home care regimen. Fortified with Sodium Hyaluronate (30%) and Pantothenic acid, it provides an especially deep and complete hydration. Because of the presence of peptides, it also assists in tightening and firming the skin while allowing for maximum absorption and effectiveness.

Designed for mature skin, this sophisticated moisturizer promotes cell renewal, stimulating the dermis layer of the skin with a high potency blend of peptides (Argireline, Matrixyl, & Biopeptide-CLTM) and botanical extracts that make it a particularly refined and effective moisturizing cream for age management.

The A&M Eye Recovery Therapy is an advanced age management treatment, applying the most tried and true peptides and delivery systems; Argireline & Matrixyl, to the highly wrinkle prone and fragile eye area, providing diminished wrinkle depth, and increased firmness and elasticity. The peptide Eyeliss is added to further enhance this treatment by counteracting skin slackening, puffiness, and decreasing irritation.

The A&M Facial Recovery Therapy is an advanced age-management treatment that blends the most tried and true peptides and delivery systems; Argireline & Matrixyl. Stimulating the deeper layers of the skin, the A&M Facial Recovery Therapy provides diminished wrinkle depth, as well as an increase in skin elasticity and firmness.

Originally designed to prepare and increase the skins receptiveness to our Professional Peptide Peel, the Premier Peptide Serum has gone on to become our most powerful anti-wrinkle product for year-round home care due to its high concentration and diversity of peptides. Composed of a total concentration of 65% peptides, the Premier Peptide Serum is a state of the art facial serum expertly formulated to reduce the signs of aging, energizing mature skin.

Directions: For mature skin types; apply at least three weeks before beginning the Lucrece Professional Peptide Peel treatment, and use twice a day leading up to the Peel. For year round application, apply once per day after the Collagen Peptide Complex. Avoid the eye area by at least 1 cm during application.

Peptides: SYN-AKE: A small peptide (Dipeptide Diaminobutyroyl Benzylamide Diacetate) that mimics the activity of Waglerin 1, a polypeptide that is found in the venom of the Temple Viper, Tropidolaemus wagleri. Clinical trials have shown SYN-AKE is capable of reducing wrinkle depth by inhibiting muscle contractions. SNAP-8: An anti-wrinkle (Acetyl Octapeptide-3) elongation of the famous Hexapeptide Argireline. The study of the basic biochemical mechanisms of anti-wrinkle activity led to the revolutionary Hexapeptide which has taken the cosmetic world by storm. ARGIRELINE: (Acetyl Hexapeptide-8) MATRIXYL: (Palmitoyl Pentapeptide-4) REGU-AGE: (Hydrolyzed Rice Bran Protein - Oxido Reductases - Soybean Protein) BIOPEPTIDE CL: (Palmitoyl Oligopeptide) RIGIN: (Palmitoyl Tetrapeptide-7) EYELISS: (Dipeptide-2 & Palmitoyl Tetrapeptide-7) INYLINE: (Acetyl Hexapeptide 30)

Other Ingredients: Water, Sodium Hyaluronate, Spiraea Ulmaria Flower Extract & Centella Asiatica Extract & Echinacea Purpurea Extract, Phenoxyethanol & Benzyl Alcohol & Potassium Sorbate & Tocopherol, Meadowsweet, Hydrocotyl Extract, Leucojum Aestivum Bulb Extract, Amino Acids, Diazolidinyl Urea, Imperata Cylindrica Extract, SMDI Copolymer, Hydroxyethylcellulose

[ pH: 5.00 ]

This unique and high potency moisturizing cream is formulated with an abundance of natural skin lighteners, peptides, and botanical extracts that combine to help clarify and energize mature skin.

Directions: Smooth a pearl size drop onto the face, gently massaging in with fingertips once per day (morning), avoiding the eye area. Follow with solar protection if applicable.

Skin Lightening Agents: Mulberry Bark, Saxifrage Extract, Grape Extract, Scutellaria Root Extracts, Vitamin C Ester (Tetrahexyldecyl Ascorbate), Emblica Fruit Extract, Licorice Root Extract.

Ingredients: Water (Aqua), Saxifrage Extract & Grape Extract & Butylene Glycol & Water & Mulberry Bark Extract & Scutellaria Root Extract, Prunus Amygdalus Dulcis (Sweet Almond) Oil, Caprylic/Capric Triglycerides, Sesamum Indicum (Sesame) Seed Oil, Cetearyl Olivate & Sorbitan Olivate, Glycerin, Palmitoyl Pentapeptide-4 (Matrixyl), Tetrahexyldecyl Ascorbate (C-Ester), Glyceryl Stearate & PEG 100 Stearate, Stearic Acid, Theobroma Cocao (Cocoa) Seed Butter, PPG-12/SMDI Copolymer, Butyrospermum Parkii (Shea) Butter, Tocopheryl Acetate (Vitamin E), Phyllanthus Emblica Fruit Extract, Palmitoyl Tripeptide-5 (Syn-Coll), Triethanolamine, Phenoxyethanol, Mangifera Indica (Mango) Seed Butter, Darutoside, Tricholoma Matsutake Singer (Mushroom) Extract, Imperata Cylindrica (Root) Extract, Fragrance (Parfum), Glucosamine HCL & Algae Extract & Yeast Extract & Urea, Retinyl Palmitate (Vitamin A), Centella Asiatica Extract & Echinacea Purpurea Extract, Xanthan Gum, Arctostaphylos Uva Ursi Leaf Extract, Glycyrrhiza Glabra Root Extract, Magnesium Aluminum Silicate, Disodium EDTA

[ pH: 5.75 ]

Specializing in firming the skin, the Collagen Peptide Complex builds off of our original Collagen Copper Activating Complex, and adds a combination of (5) major peptides, helping to keep the skin looking its youngest and most alive, as it works to firm, and add elasticity & texture to the skin. For best results, apply directly after the Nano-Peptide B5 Complex.

Directions: Apply a liberal amount on clean, dry face using fingertips, and massage into the skin. Let dry, and follow with a moisturizer and sun-block if used during the day, or the Vitamin A Facial Cream + III if used at night. Warning: For mature skin only. If redness occurs, lessen use to once or twice per week. If reactions persist, discontinue use.

Ingredients: Water (Aqua), Dipalmitoylhydroxyproline, Glycerin, Palmitoyl Tetrapeptide-7 (Rigin), Palmitoyl Oligopeptide (Biopeptide-CL), Butylene Glycol, Yeast (Faex Extract), Hydrocotyl Extract & Coneflower Extract, Aloe Barbadensis Leaf Extract, Palmitoyl Tripeptide-5 (Syn-Coll), Acetyl Hexapeptide-8 (Argireline), Palmitoyl Pentapeptide-4 (Matrixyl), Panthenol, Phenoxyethanol & Caprylyl Glycol & Ethylhexylglycerin & Hexylene Glycol, Triethanolamine, Carbomer, Decarboxy Carsonine HCI, Citrus Grandis (Grapefruit) Seed Extract, Copper PCA, Olea Europaea (Olive) Leaf Extract, Disodium EDTA

[ pH: 5.50 ]

Boasting a remarkable collection of natural and innovative ingredients from exotic plants and enhanced peptides, the neck firming cream has been designed & tested to firm and energize mature skin, while providing increased smoothness and elasticity to the often neglected neck area.

Directions: On clean dry skin, apply onto the neck area with fingertips in an upward motion. Apply twice a day, or as needed.

Key Ingredients: Bio-Bustyl: Stimulates cell metabolism, promotes collagen synthesis, and enhances fibroblast (collagen-producing cell) proliferation. INCI: Glyceryl Polymethacrylate, Soy Protein Ferment, PEG-8, & Palmitoyl Oligopeptide Polylift: Using a cross-linking technology, biopolymerization, Polylift reinforces the natural lifting effect of sweet almond proteins, providing a smooth firmness & radiance to the surface of the skin. INCI: Prunus Amygdalus Dulcis (Sweet Almond) Seed Extract.

Ingredients: Deionized Water, Prunus Amygdalus Dulcis (Sweet Almond Oil), Caprylic/Capric Triglycerides, Sesamum Indicum (Sesame) Seed Oil, Simmondsia (Jojoba) Seed Oil/ Buxus Chinensis, Cetearyl Alcohol, Dicetyl Phosphate, Ceteth-10 Phosphate, Palmitoyl Oligopeptide, Palmitoyl Tetrapeptide-7, Prunus Amygdalus Dulcis Seed Extract, Terminalia Catappa Leaf Extract & Sambucus Nigra Flower Extract & PVP & Tannic Acid, Glyceryl Polymethacrylate & Rahnella/ Soy Protein Ferment & PEG-8 & Palmitoyl Oligopeptide, Glycerin, Glyceryl Stearate & PEG 100 Stearate, Biosaccharide Gim-1, PPG-12/ SMDI Copolymer, Phyllanthus Emblica Fruit Extract, Stearic Acid, Centella Asiatica Extract & Darutosidetriethanolamine, Tocopheryl Acetate, Magnifera Indica (Mango) Seed Butter, Glycerin & Aqua & Lysolecithin & Perilla Frutescens Seed Oil, Xantham Gum, Retinyl Palmitate, Tetrahexyldecyl Ascorbate (Vitamin C Ester), Echinacea Purpurea Extract, Imperata Cylindrica (Root) Extract, Glycyrrhiza Glabra Root Extract, Magnesium, Aluminum Silicate, Disodium EDTA

[ pH: 6.25 ]

Hydration is the most essential way to keep our skin healthy feeling and healthy looking. While many of our products assist in hydrating the skin, hydration is the main focus for this product, making it an essential for all skin types. Fortified with Hyaluronic (30%) and Panthenol (Vitamin B5), the Nano-Peptide B5 Complex provides an especially deep and complete hydration. With the addition of peptides, it also assists in tightening and firming the skin while allowing for maximum absorption and effectiveness.

The Nano-Peptide B5 Complex should be applied directly after cleansing the skin, as the 2nd step in skin care regimens for all skin types (morning & night). For best results, age management regimens should follow with the Stem Cell Replenishing Serum and/or the Collagen Peptide Complex before moisturizing.

Directions: Apply a healthy amount on clean, dry skin. May be used around the eye area.

Key Ingredients: Palmitoyl Pentapeptide-4: Stimulates the skins fibroblasts to rebuild the extra-cellular matrix, including the synthesis of Collagen I and Collagen IV, fibronectin and of Glycosaminoglycans. It also stimulates the production of the dermal matrix (Collagen I & III) resulting in a significant reduction of wrinkles and fine lines. Acetyl Hexapeptide-8: Reduces facial wrinkle depth and the signs of skin aging resulting from facial movements and facial muscle contraction by halting the release of neurotransmitters from SNARE and catecholamine complexes, (which can also induce formation of wrinkles and fine lines to the skin). Hyaluronic Acid (30%): Penetrates deep into the skin, providing ample moisture Panthenol: Enhances formation of skin pigments for younger looking skin, and contains deep penetrating properties that allow a more complete hydration.

Other Ingredients: Water (Aqua), Hyaluronic Acid, Panthenol (Vitamin B5), MDI Complex, Palmitoyl Pentapeptide-4, Acetyl Hexapeptide-8, Phenoxyethanol, Hydrolyzed Wheat Protein, Butylene Glycol, Hydrocotyl & Coneflower Extract, Glycosaminoglycans.

[ pH: 5.5 ]

Designed for mature, sun damaged, and/or dehydrated skin, the Anti-Wrinkle Facial Cream is a peptide enriched moisturizer focused on increasing skin firmness & elasticity, and fortifying the skin with anti-oxidants & botanical extracts to facilitate healthy feeling and healthy looking skin.

Directions: Smooth a pearl size drop onto the face, massage into skin thoroughly. For use in the morning (recommended), follow with solar protection.

Ingredients: Water (Aqua), Glycerin, Dimethicone, Caprylic/Capric Triglycerides, C12-15 Alkyl Benzoate, Linoleic Acid & Glycine Soja (Soybean) Sterols & Phospholipids, Acetyl Hexapeptide-8, Butylene Glycol & Carbomer & Polysorbate 20 & Palmitoyl Pentapeptide-4, Cetearyl Alcohol & Dicetyl Phosphate & Ceteth-10 Phosphate, Glyceryl Stearate & PEG 100 Stearate, PPG-12/ SMDI Copolymer, Phyllanthus Emblica Fruit Extract, Darutoside, Cocoa Butter, Cetyl Alcohol, Butyrospermum Parkii (Shea Butter), Saccharomyces/Xylinum Black Tea Ferment & Glycerin & Hydroxyethylcellulose, Glucoseamine HCL & Algae Extract & Saccharomyces Cerevisiae (Yeast Extract) & Urea, Steareth-20 & Palmitoyl Tetrapeptide-7, Centella Asiatica Extract & Echinacea Purpurea Extract, Hydrolyzed Vegetable Protein, Imperata Cylindrica (Root) Extract & PEG-8 & Carbomer, Phenoxyethanol & Caprylyl Glycol & Ethylhexylglycerin & Hexylene Glycol, Polyglyceryl Methacrylate & Propylene Glycol & Palmitoyl Oligopeptide, Cyclopentasiloxane & Dimethicone, Stearic Acid, Mangifera Indica (Mango) Seed Butter, Tocopheryl Acetate, Glycyrrhiza Glabra Root Extract, Arctostaphylos Uva Ursi Leaf Extract, Chlorella Vulgaris Extract, Corallina Officinalis Extract, Dipotassium Glycyrrhizate, PEG-8 & Tocopherol & Ascorbyl Palmitate & Ascorbic Acid & Citric Acid, Disodium EDTA, Magnesium Aluminum Silicate, Xanthan Gum, Triethanolamine, Retinyl Palmitate, Lavandula Angustifolia (Lavender) Oil

[ pH: 5.75 ]

This advanced eye care treatment is expertly formulated to diminish the depth, increase firmness & elasticity, and to counteract skin slackening to the highly wrinkle prone and fragile eye area. Featuring (4) major peptides (Argireline, Matrixyl, Eyeliss, & Regu-age), the A&M Eye Recovery Therapy is our most potent eye treatment, and is recommended for mature skin.

Directions: Using fingertips, massage to surrounding eye areas affected by wrinkles due to muscle contractions. Also use in the nasal labial area. For best results, apply once per evening, followed by the A&M Facial Recovery Therapy, and/or the Vitamin A Facial Cream + III.

Ingredients Highlights: Palmitoyl Pentapeptide-4 (Matrixyl): Stimulates the skins fibroblasts to rebuild the extra-cellular matrix, including the synthesis of Collagen I and Collagen IV, fibronectin and of Glycosaminoglycans. It also stimulates the production of dermal matrix (Collagen I & III) resulting in a significant reduction of wrinkles and fine lines of the skin. Acetyl Hexapeptide-8 (Argireline): Reduces facial wrinkle depth and the signs of skin aging resulting from facial movements and facial muscle contraction by halting the release of neurotransmitters from SNARE and catecholamine complexes, (which can also induce formation of wrinkles and fine lines to the skin). Dipeptide-2 & Palmitoyl Tetrapeptide-7 (Eyeliss): Combats the effect of tiredness and hypertension, as well as the natural effects of aging, which contribute to the formation of bags under the eyes, Eyeliss is an outstanding anti-aging ingredient. Soy Peptides & Hydrolyzed Rice Bran Extract (Regu-Age): A highly active complex of specially purified soy and rice peptides and biotechnologically derived yeast protein, Regu-Age effectively addresses dark circles and puffiness around the eyes.

Other Ingredients: Water, Sodium Hyaluronate, Centella Asiatica Extract & Echinacea Purpurea Extract, Xanthan Gum-Chondrus Crispus & Glucose, Lecithin & Dipalmitoyl Hydroxyproline, Imperata Cylindrica Extract, PEG-8 Dimethicone, Cyclomethicone

[ pH: 6.25 ]

An advanced age management treatment that blends the most tried and true peptides and delivery systems, Argireline & Matrixyl, helping to prevent skin aging induced by repeated facial movement caused by excessive catecholamine release. Stimulating the deeper layers of the skin, the A&M Facial Recovery Therapy provides diminished wrinkle depth, as well as an increase in the elasticity and firmness of the skin. Recommend for mature skin types.

Directions: Using fingertips apply to facial areas and massage into skin once per evening, allowing it to absorb into the skin. Apply directly after the A&M Eye Recovery Therapy.

Ingredients Highlights: Palmitoyl Pentapeptide-4: Stimulates the skins fibroblasts to rebuild the extra-cellular matrix, including the synthesis of Collagen I and Collagen IV, fibronectin and of Glycosaminoglycans. It also stimulates the production of dermal matrix (Collagen I & III) resulting in a significant reduction of wrinkles and fine lines of the skin. Acetyl Hexapeptide-8: Reduces facial wrinkle depth and the signs of skin aging resulting from facial movements and facial muscle contraction by halting the release of neurotransmitters from SNARE and catecholamine complexes, (which can also induce formation of wrinkles and fine lines to the skin).

Other Ingredients: Deionized Water, Sodium Hyaluronate, Lecithin & Dipalmitoyl Hydroxyproline, Hydrocotyl & Coneflower Extracts, Glycosaminoglycans, Glucosamine HCI & Alagae Extract & Yeast Extract & Urea, Magnesium Ascorbyl Phosphate, Glycine HCL, Retinyl Palmitate

[ pH: 6.25 ]

Addressing the multiple problems of sun and age damaged skin, the Intensive Clarifying Facial Cream + III is a glycolic acid based moisturizer featuring three potent skin lighteners; Kojic Acid, Licorice, and Hydro- quinone (2%), which quickly & effectively treat hyperpigmentation & discolorations.

Vitamin C Ester (Tetrahexyldecyl Ascorbate) is a stable, oil-soluble form of Vitamin C, providing high level skin lightening, enhanced collagen synthesis, and increased DNA & UV protection with higher absorption capabilities and less irritating than Ascorbic Acid.

Because of how well it protects the skins collagen fibers, ascorbic acid based Vitamin C is widely considered one of the most effective antioxidants for skin rejuvenation & revitalization. The 20% Vitamin C Lightening drops combine a potent concentration of ascorbic acid with aloe, green tea leaf extract, and mushroom extract. *Also available is our original Vitamin C Serum, containing a milder blend of ascorbic acid (14%).

The Anti-Wrinkle Eye Cream contains a high potency blend of peptides, including EyelissTM & Regu-age (in addition to Argireline & Matrixyl) which work synergistically to improve firmness, elasticity, and reduce puffiness & dark circles around the eye area.

Addressing the multiple problems of sun and age damaged skin, the Intensive Clarifying Facial Cream + III moisturizer combines three powerful lightening. Agents: Hydroquinone, Kojic Acid, & Licorice, with Alpha Lipoic Acid, Vitamin C, & Co-enzyme Q10, minimizing fine lines, evening skin tone, and naturally exfoliating the outer layer of the skin while providing a 15 sun protection factor (SPF).

Directions: Smooth a pearl sized drop onto the face once or twice daily. Avoid eye area. If used during the day, apply additional sun protection if skin is in contact with the sun for an extended period (twenty minutes or more).

Active Ingredients: Octyl Methoxycinnamate - 7.5% Octyl Salcylate - 5% Glycolic Acid - 4% Benzophenone - 3% Hydroquinone - 2%

Inactive Ingredients: Deionized Water, Glyceryl Stearate & PEG-100 Stearate, Ascorbic Acid (Vitamin C), Alpha Lipoic Acid, Co-enzyme Q 10, Kojic Acid, Cetyl Alcohol, Licorice, Palmitic Acid, Octyl Salcylate, Phenoxyethanol, Tocopheryl Acetate, Essential Oil of Rosewood, Disodium tEDTA

[ pH: 4.5 ]

Vitamin C Ester is a stable, oil-soluble form of Vitamin C, providing high level Skin Lightening, enhanced Collagen Synthesis, and increased DNA & UV protection with higher absorption capabilities than Ascorbic Acid.

Directions: On clean, dry skin, apply four to five drops directly onto the face once a day, avoiding the eye area.

Ingredients: Cyclomethicone, Tetrahexyldecyl Ascorbate (Vitamin C Ester 10%), PPG-12/SMDI Copolymer, Santalum Album Extract, Phellodendrone Amurense Bark Extract, Barley Extract, Jojoba Seed Oil/Buxus Chinensis, Tocopheryl Acetate, Phenoxyethanol, Tricholoma Matsutake Singer (Mushroom Extract), Ascorbyl Palmitate, Bisabolol

[ pH: 7.0 ]

Ascorbic acid based Vitamin C is widely considered one of the most effective antioxidants for rejuvenating mature skin due to its ability to protect the skins collagen fibers, and for its ability to help inhibit melanin production, creating a lightening effect to the skin. The 20% Vitamin C Lightening Drops combine a potent concentration of ascorbic acid with aloe, green tea extract, and an exotic mushroom extract (Tricholoma Matsutake Singer) for additional lightening.

Directions: On clean, dry skin apply four to five drops directly onto the face once daily. Avoid the eye area. Thoroughly wash hands after use. Though a light tingling sensation is normal, if irritation (redness) results after application, discontinue or reduce the frequency of use of the product.

Ingredients: Water (Aqua), Ascorbic Acid -20%, Ethoxydiglycol, Hydroxyethylcellulose, Phenoxyethanol, Polysorbate 20, Camellia Sinensis Leaf Extract, Aloe Barbadensis Leaf Extract, Mushroom Extract (Tricholoma Matsutake Singer)-Enzymes- Alcohol, Sodium Sulfite, Disodium EDTA

[ pH: 3.00 ]

The Anti-Wrinkle Eye Cream is formulated to reduce puffiness, enhances firmness, strengthens connective tissues, and to help diminish dark circles around the eye area. In contrast to the A&M Eye Recovery Therapy, the Anti-Wrinkle Eye Cream concentrates on the upper layers of the skin, making it a great day moisturizer for the eyes.

Directions: Apply around the eye area with the ring finger once daily. For best results, follow with a moisturizer and solar protection.

Go here to read the rest:
anti-aging stem cells - innovative treatments for skin ...

Mary Shomon

Acquired immunodeficiency syndrome (AIDS):A life-threatening disease caused by a virus and characterized by breakdown of the body's immune defenses.

Active immunity:Immunity produced by the body in response to stimulation by a disease-causing organism or a vaccine.

Agammaglobulinemia:An almost total lack of immunoglobulins, or antibodies.

Allergen:Any substance that causes an allergy.

Allergy:An inappropriate and harmful response of the immune system to normally harmless substances.

Anaphylactic shock:A life-threatening allergic reaction characterized by a swelling of body tissues including the throat, difficulty in breathing, and a sudden fall in blood pressure.

Anergy:A state of unresponsiveness, induced when the T cell's antigen receptor is stimulated, that effectively freezes T cell responses pending a "second signal" from the antigen-presenting cell (co-stimulation).

Antibody:A soluble protein molecule produced and secreted by B cells in response to an antigen, which is capable of binding to that specific antigen.

Antibody-dependent cell-mediated cytotoxicity (ADCC):An immune response in which antibody, by coating target cells, makes them vulnerable to attack by immune cells.

Antigen:Any substance that, when introduced into the body, is recognized by the immune system.

Antigen-presenting cells:B cells, cells of the monocyte lineage (including macrophages as well as dendritic cells), and various other body cells that "present" antigen in a form that T cells can recognize.

Antinuclear antibody (ANA):An autoantibody directed against a substance in the cell's nucleus.

Antiserum:Serum that contains antibodies.

Antitoxins:Antibodies that interlock with and inactivate toxins produced by certain bacteria.

Appendix:Lymphoid organ in the intestine.

Attenuated:Weakened; no longer infectious.

Autoantibody:An antibody that reacts against a person's own tissue.

Autoimmune disease:A disease that results when the immune system mistakenly attacks the body's own tissues. Rheumatoid arthritis and systemic lupus erythematosus are autoimmune diseases.

Bacterium:A microscopic organism composed of a single cell. Many but no all bacteria cause disease.

Basophil:A white blood cell that contributes to inflammatory reactions. Along with mast cells, basophils are responsible for the symptoms of allergy.

B cells:Small white blood cells crucial to the immune defenses. Also known as B lymphocytes, they are derived from bone marrow and develop into plasma cells that are the source of antibodies.

Biological response modifiers:Substances, either natural or synthesized, that boost, direct, or restore normal immune defenses. BRMs include interferons, interleukins, thymus hormones, and monoclonal antibodies.

Biotechnology:The use of living organisms or their products to make or modify a substance. Biotechnology includes recombinant DNA techniques (genetic engineering) and hybridoma technology.

Bone marrow:Soft tissue located in the cavities of the bones. The bone marrow is the source of all blood cells.

Cellular immunity:Immune protection provided by the direct action of immune cells (as distinct from soluble molecules such as antibodies).

Chromosomes:Physical structures in the cell's nucleus that house the genes. Each human cell has 23 pairs of chromosomes.

Clone:(n.)A group of genetically identical cells or organisms descended from a single common ancestor; (v.) to reproduce multiple identical copies.

Complement:A complex series of blood proteins whose action "complements" the work of antibodies. Complement destroys bacteria, produces inflammation, and regulates immune reactions.

Complement cascade:A precise sequence of events usually triggered by an antigen-antibody complex, in which each component of the complement system is activated in turn.

Constant region:That part of an antibody's structure that is characteristic for each antibody class.

Co-Stimulation:The delivery of a second signal from an antigen-presenting cell to a T cell. The second signal rescues the activated T cell from anergy, allowing it to produce the lymphokines necessary for the growth of additional T cells.

Cytokines:Powerful chemical substances secreted by cells. Cytokines include lymphokines produced by lymphocytes and monokines produced by monocytes and macrophages.

Cytotoxic T cells:A subset of T lymphocytes that can kill body cells infected by viruses or transformed by cancer.

Dendritic cells:White blood cells found in the spleen and other lymphoid organs. Dendritic cells typically use threadlike tentacles to enmesh antigen, which they present to T cells.

DNA (deoxyribonucleic acid):Nucleic acid that is found in the cell nucleus and that is the carrier of genetic information.

Enzyme:A protein, produced by living cells, that promotes the chemical processes of life without itself being altered.

Eosinophil:A white blood cell that contains granules filled with chemicals damaging to parasites, and enzymes that damp down inflammatory reactions.

Epitope:A unique shape or marker carried on an antigen's surface, which triggers a corresponding antibody response.

Fungus:Member of a class of relatively primitive vegetable organism. Fungi include mushrooms, yeasts, rusts, molds, and smuts.

Gene:A unit of genetic material (DNA) that carries the directions a cell uses to perform a specific function, such as making a given protein.

Graft-versus-host disease (GVHD):A life-threatening reaction in which transplanted immunocompetent cells attack the tissues of the recipient.

Granulocytes:White blood cells filled with granules containing potent chemicals that allow the cells to digest microorganisms, or to produce inflammatory reactions. Neutrophils, eosinophils, and basophils are examples of granulocytes.

Helper T cells:A subset of T cells that typically carry the T4 marker and are essential for turning on antibody production, activating cytotoxic T cells, and initiating many other immune responses.

Hematopoiesis:The formation and development of blood cells, usually takes place in the bone marrow.

Histocompatibility testing:A method of matching the self antigens (HLA) on the tissues of a transplant donor with those of the recipient. The closer the match, the better the chance that the transplant will take.

HIV (human immunodeficiency virus):The virus that causes AIDS.

Human leukocyte antigens (HLA):Protein in markers of self used in histocompatibility testing. Some HLA types also correlate with certain autoimmune diseases.

Humoral immunity:Immune protection provided by soluble factors such as antibodies, which circulate in the body's fluids or "humors," primarily serum and lymph.

Hybridoma:A hybrid cell created by fusing a B lymphocyte with a long-lived neoplastic plasma cell, or a T lymphocyte with a lymphoma cell. A B-cell hybridoma secretes a single specific antibody.

Hypogammaglobulinemia:Abno rmally low levels of immunoglobulins.

Idiotypes:The unique and characteristic parts of an antibody's variable region, which can themselves serve as antigens.

Immune complex:A cluster of interlocking antigens and antibodies.

Immune response:The reactions of the immune system to foreign substances.

Immunoassay:A test using antibodies to identify and quantify substances. Often the antibody is linked to a marker such as a fluorescent molecule, a radioactive molecule, or an enzyme.

Immunocompetent:Capable of developing an immune response.

Immunoglobulins:A family of large protein molecules, also known as antibodies.

Immunosuppression:Reduction of the immune responses, for instance by giving drugs to prevent transplant rejection.

Immunotoxin:A monoclonal antibody linked to a natural toxin, a toxic drug, or a radioactive substance.

Inflammatory response:Redness, warmth, swelling, pain, and loss of function produced in response to infection, as the result of increased flood flow and an influx of immune cells and secretions.

Interleukins:A major group of lymphokines and monokines.

Kupffer cells:Specialized macrophages in the liver.

LAK cells:Lymphocytes transformed in the laboratory into lymphokine-activated killer cells, which attack tumor cells.

Langerhans cells:Dendritic cells in the skin that pick up antigen and transport it to lymph nodes.

Leukocytes:All white blood cells.

Lymph:A transparent, slightly yellow fluid that carries lymphocytes, bathes the body tissues, and drains into the lymphatic vessels.

Lymphatic vessels:A bodywide network of channels, similar to the blood vessels, which transport lymph to the immune organs and into the bloodstream.

Lymph nodes:Small bean-shaped organs of the immune system, distributed widely throughout the body and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells.

Lymphocytes:Small white blood cells produced in the lymphoid organs and paramount in the immune defenses.

Lymphoid organs:The organs of the immune system, where lymphocytes develop and congregate. They include the bone marrow, thymus, lymph nodes, spleen, and various other clusters of lymphoid tissue. The blood vessels and lymphatic vessels can also be considered lymphoid organs.

Lymphokines:Powerful chemical substances secreted by lymphocytes. These soluble molecules help direct and regulate the immune responses.

Macrophage:A large and versatile immune cell that acts as a microbe-devouring phagocyte, an antigen-presenting cell, and an important source of immune secretions.

Major histocompatibility complex (MHC):A group of genes that controls several aspects of the immune response. MHC genes code for self markers on all body cells.

Mast cell:A granule-containing cell found in tissue. The contents of mast cells, along with those of basophils, are responsible for the symptoms of allergy.

Microbes:Minute living organisms, including bacteria, viruses, fungi and protozoa.

Microorganisms:Microscopic plants or animals.

Molecule:The smallest amount of a specific chemical substance that can exist alone. (The break a molecule down into its constituent atoms is to change its character. A molecule of water, for instance, reverts to oxygen and hydrogen.)

Monoclonal antibodies:Antibodies produced by a single cell or its identical progeny, specific for a given antigen. As a tool for binding to specific protein molecules, monoclonal antibodies are invaluable in research, medicine, and industry.

Monocyte:A large phagocytic white blood cell which, when it enters tissue, develops into a macrophage.

Monokines:Powerful chemical substances secreted by monocytes and macrophages. These soluble molecules help direct and regulate the immune responses.

Natural killer (NK) cells:Large granule-filled lymphocytes that take on tumor cells and infected body cells. They are known as "natural" killers because they attack without first having to recognize specific antigens.

Neutrophil:A white blood cell that is an abundant and important phagocyte.

Nucleic acids:Large, naturally occurring molecules composed of chemical building blocks known as nucleotides. There are two kinds of nucleic acids, DNA and RNA.

OKT3:A monoclonal antibody that targets mature T cells.

Opportunistic infection:An infection in an immunosuppressed person caused by an organism that does not usually trouble people with healthy immune systems.

Opsonize:To coat an organism with antibodies or a complement protein so as to make it palatable to phagocytes.

Organism:An individual living thing.

Parasite:A plant or animal that lives, grows and feeds on or within another living organism.

Passive immunity:Immunity resulting from the transfer of antibodies or antiserum produced by another individual.

Peyer's patches:A collection of lymphoid tissues in the intestinal tract.

Phagocytes:Large white blood cells that contribute to the immune defenses by ingesting microbes or other cells and foreign particles.

Plasma cells:Large antibody-producing cells that develop from B cells.

Platelets:Granule-containing cellular fragments critical for blood clotting and sealing off wounds. Platelets also contribute to the immune response.

Polymorphs:Short for polymorphonuclear leukocytes or granulocytes.

Proteins:Organic compounds made up of amino acids. Proteins are one of the major constituents of plant and animal cells.

Protozoa:A group of one-celled animals, a few of which cause human disease (including malaria and sleeping sickness).

Rheumatoid factor:An autoantibody found in the serum of most persons with rheumatoid arthritis.

RNA (ribonucleic acid):A nucleic acid that is found in the cytoplasm and also in the nucleus of some cells. One function of RNA is to direct the synthesis of proteins.

Scavenger cells:Any of a diverse group of cells that have the capacity to engulf and destroy foreign material, dead tissues, or other cells.

SCID mouse:A laboratory animal that, lacking an enzyme necessary to fashion an immune system of its own, can be turned into a model of the human immune system when injected with human cells or tissues.

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A Comprehensive Guide to Understanding the Immune System

Find your glossary term by first letter:

a form of complementary and alternative medicine that involves inserting thin needles through the skin at specific points on the body to control pain and other symptoms.

written instructions letting others know the type of care you want if you are seriously ill or dying. These include a living will and health care power of attorney.

disorders that involve an immune response in the body. Allergies are reactions to allergens such as plant pollen, other grasses and weeds, certain foods, rubber latex, insect bites, or certain drugs.

tiny glands in the breast that produce milk.

a brain disease that cripples the brain's nerve cells over time and destroys memory and learning. It usually starts in late middle age or old age and gets worse over time. Symptoms include loss of memory, confusion, problems in thinking, and changes in language, behavior, and personality.

clear, slightly yellowish liquid that surrounds the unborn baby (fetus) during pregnancy. It is contained in the amniotic sac.

when the amount of red blood cells or hemoglobin (the substance in the blood that carries oxygen to organs) becomes reduced, causing fatigue that can be severe.

the use of medicine to prevent the feeling of pain or another sensation during surgery or other procedures that might be painful.

a thin or weak spot in an artery that balloons out and can burst.

anticancer drugs that can stop or slow down biochemical reactions in cells.

drugs that inhibit the ability of HIV or other types of retroviruses to multiply in the body.

the body opening from which stool passes from the lower end of the intestine and out of the body.

a form of complementary and alternative medicine in which the scent of essential oils from flowers, herbs, and trees is inhaled to promote health and well-being.

blood vessels that carry oxygen and blood to the heart, brain and other parts of the body.

technology that involves procedures that handle a woman's eggs and a man's sperm to help infertile couples conceive a child.

dry and itchy skin, caused by certain diseases, irritating substances, allergies, or a persons genetic makeup.

a medical condition in kids and adults that makes it hard to sit still, pay attention, and focus on certain tasks.

a condition in which abnormal breast cells are found in either the breast lobules (atypical lobular hyperplasia) or the breast ducts (atypical ductal hyperplasia). Atypical hyperplasia is not cancer. But having it increases breast cancer risk.

blood proteins made by the body's immune system that are meant to neutralize and destroy germs or other foreign substances but instead attack healthy cells of the body.

an immune response by the body against one of its own tissues, cells, or molecules.

disease caused by an immune response against foreign substances in the tissues of one's own body.

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microorganisms that can cause infections.

noncancerous

a type of medication that reduces nerve impulses to the heart and blood vessels. This makes the heart beat slower and with less force. Blood pressure drops and the heart works less hard.

a brown liquid made by the liver. It contains some substances that break up fat for digestion, while other substances are waste products.

when the hemoglobin in a person's blood breaks down, causing a yellowing of the skin and whites of the eyes. It is a temporary condition in newborn infants.

an eating disorder caused by a person being unable to control the need to overeat.

having to do with, or related to, living things.

removal of a small piece of tissue for testing or examination under a microscope.

medical illness that causes unusual shifts in mood, energy, and activity levels. It is also known as manic-depressive illness. A person with bipolar disorder may switch from feeling extremely joyful or excited to feeling extremely sad and hopeless very quickly.

a special place for women to give birth. They have all the required equipment for birthing, but are specially designed for a woman, her partner, and family. Birth centers may be free standing (separate from a hospital) or located within a hospital.

the organ in the human body that stores urine. It is found in the lower part of the abdomen.

fluid in the body made up of plasma, red and white blood cells, and platelets. Blood carries oxygen and nutrients to and waste materials away from all body tissues. In the breast, blood nourishes the breast tissue and provides nutrients needed for milk production.

blood pressure is the force of blood against the walls of arteries. Blood pressure is noted as two numbersthe systolic pressure (as the heart beats) over the diastolic pressure (as the heart relaxes between beats). The numbers are written one above or before the other, with the systolic number on top and the diastolic number on the bottom. For example, a blood pressure reading of 120/80 mmHg (millimeters of mercury) is called 120 over 80.

the transfer of blood or blood products from one person (donor) into another person's bloodstream (recipient). Most times, it is done to replace blood cells or blood products lost through severe bleeding. Blood can be given from two sources, your own blood (autologous blood) or from someone else (donor blood).

how a person feels about how she or he looks.

a measure of body fat based on a person's height and weight.

also known as the intestine, which is a long tube-like organ in the human body that completes digestion or the breaking down of food. The small bowel is the small intestine and the large bowel is the large intestine.

inflammation of the main air passages (bronchi) to your lungs. It causes cough, shortness of breath, and chest tightness.

an eating disorder caused by a person consuming an extreme amount of food all at once followed by self-induced vomiting or other purging.

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a unit of energy-producing potential in food.

a term for diseases in which abnormal cells in the body divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymphatic system, which is a network of tissues that clears infections and keeps body fluids in balance.

compounds such as sugars and starches that occur in food and are broken down to release energy in the body.

disease of the heart and blood vessels.

a sudden loss of motor tone and strength.

cloudy or thick areas in the lens of the eye.

disease of the blood vessels in the brain.

procedure where the baby is delivered through an abdominal incision. Also called cesarean delivery or cesarean birth.

treatment with anticancer drugs.

an alternative medical system that takes a different approach from standard medicine in treating health problems. The goal of chiropractic therapy is to normalize this relationship between your body's structure (mainly the spine) and its function. Chiropractic professionals use a type of hands-on therapy called spinal manipulation or adjustment.

If necessary this test is performed between 10 and 12 weeks of pregnancy and can indicate the same chromosomal abnormalities and genetic disorders as amniocentesis can. It also can detect the baby's sex and risk of spina bifida.

long-lasting, such as a chronic illness or chronic disease.

a complex disorder characterized by extreme fatigue that lasts six months or longer, and does not improve with rest or is worsened by physical or mental activity. Other symptoms can include weakness, muscle pain, impaired memory and/or mental concentration, and insomnia. The cause is unknown.

birth defects that affect the upper lip and the hard and soft palates of the mouth. Features range from a small notch in the lip to a complete fissure or groove, extending into the roof of the month and nose. These features may occur separately or together.

an external female sex organ located near the top of the inner labia of the vagina. The clitoris is very sensitive to the touch, and for most women it is a center of sexual pleasure.

to force someone to do something that they do not want to do.

a diagnostic procedure in which a flexible tube with a light source in inserted into the colon (large intestine or large bowel) through the anus to view all sections of the colon for abnormalities.

thick, yellowish fluid secreted from breast during pregnancy, and the first few days after childbirth before the onset of mature breast milk. Also called first milk, it provides nutrients and protection against infectious diseases.

abnormalities of the heart's structure and function caused by abnormal or disordered heart development before birth.

a type of body tissue that supports other tissues and binds them together. Connective tissue provides support in the breast.

infrequent or hard stools or difficulty passing stools.

transmitted by direct or indirect contact.

usually has a master's degree in Counseling and has completed a supervised internship.

an ongoing condition that causes inflammation of the digestive tract, also called the GI tract. It can affect any part of the GI tract from the mouth to the anus. It often affects the lower part of the small intestine, causing pain and diarrhea.

one of the most common serious genetic (inherited) diseases. One out of every 400 couples is at risk for having children with CF. CF causes the body to make abnormal secretions leading to mucous build-up. CF mucous build-up can impair organs such as the pancreas, the intestine and the lungs.

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impairs the vitality and strength of a person.

medications that treat cough and stuffy nose by shrinking swollen membranes in the nose and making it easier to breath.

excessive loss of body water that the body needs to carry on normal functions at an optimal level. Signs include increasing thirst, dry mouth, weakness or lightheadedness (particularly if worse on standing), and a darkening of the urine or a decrease in urination.

when a person believes something that is not true and that person keeps the belief even though there is strong evidence against it. Delusions can be the result of brain injury or mental illness.

a square, thin piece of latex that can be placed over the anus or the vagina before oral sex.

term used to describe an emotional state involving sadness, lack of energy and low self-esteem.

medical treatment used when kidneys fail. Special equipment filters the blood to rid the body of harmful wastes, salt, and extra water.

tube through which food passes and is digested, and wastes are eliminated. The digestive tract runs from the mouth to the anus and includes the esophagus, stomach, and intestines.

a physical or mental impairment that interferes with or prevents normal achievement in a particular function.

a lab test in which a patient's DNA is tested. DNA is a molecule that has a person's genetic information and is found in every cell in a person's body.

Down syndrome is the most frequent genetic cause for mild to moderate mental retardation and related medical problems. It is caused by a chromosomal abnormality. For an unknown reason, a change in cell growth results in 47 instead of the usual 46 chromosomes. This extra chromosome changes the orderly development of the body and brain.

a condition in which abnormal cells are found in the lining of breast ducts. These cells have not spread outside the duct to the surrounding breast tissue. DCIS is not cancer. But some cases of DCIS become breast cancer over time, so its important to get treatment for DCIS.

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an external, noninvasive test that records the electrical activity of the heart.

a period during pregnancy where the baby has rapid growth, and the main external features begin to take form.

a condition caused by damage to the air sacs in the lungs. This damage keeps the body from getting enough oxygen. Symptoms include trouble breathing, cough, and trouble exercising for more than brief periods. Emphysema is usually caused by smoking.

a diagnostic procedure in which a thin, flexible tube is introduced through the mouth or rectum to view parts of the digestive tract.

during labor a woman may be offered an epidural, where a needle is inserted into the epidural space at the end of the spine, to numb the lower body and reduce pain. This allows a woman to have more energy and strength for the end stage of labor, when it is time to push the baby out of the birth canal.

inability to achieve and keep a penile erection.

tube that connects the throat with the stomach.

when someone exposes him/herself in public

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a federal regulation that allows eligible employees to take up to 12 work weeks of unpaid leave during any 12 month period for the serious health condition of the employee, parent, spouse or child, or for pregnancy or care of a newborn child, or for adoption or foster care of a child.

a rare, inherited blood disorder that leads to bone marrow failure. FA causes your bone marrow to stop making enough new blood cells for your body to work normally. The risk for some cancers is much greater for people with FA.

a source of energy used by the body to make substances it needs. Fat helps your body absorb certain vitamins from food. Some fats are better for your health than others. To help prevent heart disease and stroke, most of the fats you eat should be monounsaturated (mon-oh-uhn-SACH-uh-ray-tid) and polyunsaturated (pol-ee-uhn-SACH-uh-ray-tid) fats.

a feeling of lack of energy, weariness or tiredness.

a barrier form of birth control that is worn by the woman inside her vagina. It is made of thin, flexible, manmade rubber. It keeps sperm from getting into her body.

a term used to describe the full range of harmful effects that can occur when a fetus is exposed to alcohol.

body temperature is raised above normal and is usually a sign of infection or illness.

a disorder that causes aches and pain all over the body, and involves tender points on specific places on the neck, shoulders, back, hips, arms, and legs that hurt when pressure is put on them.

each month, an egg develops inside the ovary in a fluid filled pocket called a follicle. This follicle releases the egg into the fallopian tube.

Read more here:
Glossary Index | womenshealth.gov

Adult stem cellsee somatic stem cell.

Astrocytea type of supporting (glial) cell found in the nervous system.

BlastocoelThe fluid-filled cavity inside the blastocyst, an early, preimplantation stage of the developing embryo.

BlastocystA preimplantation embryo of about 150 cells produced by cell division following fertilization. The blastocyst is a sphere made up of an outer layer of cells (the trophoblast), a fluid-filled cavity (the blastocoel), and a cluster of cells on the interior (the inner cell mass).

Bone marrow stromal cellsA population of cells found in bone marrow that are different from blood cells, a subset of which are multipotent stem cells, able to give rise to bone, cartilage, marrow fat cells, and able to support formation of blood cells.

Bone marrow stromal cellsA population of cells found in bone marrow that are different from blood cells, a subset of which are multipotent stem cells, able to give rise to bone, cartilage, marrow fat cells, and able to support formation of blood cells.

Bone marrow stromal stem cells (skeletal stem cells)A multipotent subset of bone marrow stromal cells able to form bone, cartilage, stromal cells that support blood formation, fat, and fibrous tissue.

Cell-based therapiesTreatment in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cells or tissues.

Cell cultureGrowth of cells in vitro in an artificial medium for research or medical treatment.

Cell divisionMethod by which a single cell divides to create two cells. There are two main types of cell division depending on what happens to the chromosomes: mitosis and meiosis.

Chromosomea structure consisting of DNA and regulatory proteins found in the nucleus of the cell. The DNA in the nucleus is usually divided up among several chromosomes.The number of chromosomes in the nucleus varies depending on the species of the organism. Humans have 46 chromosomes.

Clone (v) To generate identical copies of a region of a DNA molecule or to generate genetically identical copies of a cell, or organism; (n) The identical molecule, cell, or organism that results from the cloning process.

CloningSee Clone.

Cord blood stem cellsSee Umbilical cord blood stem cells.

Culture mediumThe liquid that covers cells in a culture dish and contains nutrients to nourish and support the cells. Culture medium may also include growth factors added to produce desired changes in the cells.

DifferentiationThe process whereby an unspecialized embryonic cell acquires the features of a specialized cell such as a heart, liver, or muscle cell. Differentiation is controlled by the interaction of a cell's genes with the physical and chemical conditions outside the cell, usually through signaling pathways involving proteins embedded in the cell surface.

Directed differentiationThe manipulation of stem cell culture conditions to induce differentiation into a particular cell type.

DNADeoxyribonucleic acid, a chemical found primarily in the nucleus of cells. DNA carries the instructions or blueprint for making all the structures and materials the body needs to function. DNA consists of both genes and non-gene DNA in between the genes.

EctodermThe outermost germ layer of cells derived from the inner cell mass of the blastocyst; gives rise to the nervous system, sensory organs, skin, and related structures.

EmbryoIn humans, the developing organism from the time of fertilization until the end of the eighth week of gestation, when it is called a fetus.

Embryoid bodiesRounded collections of cells that arise when embryonic stem cells are cultured in suspension. Embryoid bodies contain cell types derived from all 3 germ layers.

Embryonic germ cellsPluripotent stem cells that are derived from early germ cells (those that would become sperm and eggs). Embryonic germ cells (EG cells) are thought to have properties similar to embryonic stem cells.

Embryonic stem cellsPrimitive (undifferentiated) cells derived from a 5-day preimplantation embryo that are capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers.

Embryonic stem cell lineEmbryonic stem cells, which have been cultured under in vitro conditions that allow proliferation without differentiation for months to years.

EndodermThe innermost layer of the cells derived from the inner cell mass of the blastocyst; it gives rise to lungs, other respiratory structures, and digestive organs, or generally "the gut."

Enucleatedhaving had its nucleus removed.

Epigenetichaving to do with the process by which regulatory proteins can turn genes on or off in a way that can be passed on during cell division.

Feeder layerCells used in co-culture to maintain pluripotent stem cells. For human embryonic stem cell culture, typical feeder layers include mouse embryonic fibroblasts (MEFs) or human embryonic fibroblasts that have been treated to prevent them from dividing.

FertilizationThe joining of the male gamete (sperm) and the female gamete (egg).

FetusIn humans, the developing human from approximately eight weeks after conception until the time of its birth.

GameteAn egg (in the female) or sperm (in the male) cell. See also Somatic cell.

Gastrulationthe process in which cells proliferate and migrate within the embryo to transform the inner cell mass of the blastocyst stage into an embryo containing all three primary germ layers.

GeneA functional unit of heredity that is a segment of DNA found on chromosomes in the nucleus of a cell. Genes direct the formation of an enzyme or other protein.

Germ layersAfter the blastocyst stage of embryonic development, the inner cell mass of the blastocyst goes through gastrulation, a period when the inner cell mass becomes organized into three distinct cell layers, called germ layers. The three layers are the ectoderm, the mesoderm, and the endoderm.

Hematopoietic stem cellA stem cell that gives rise to all red and white blood cells and platelets.

Human embryonic stem cell (hESC)A type of pluripotent stem cell derived from the inner cell mass (ICM) of the blastocyst.

Induced pluripotent stem cellsSomatic (adult) cells reprogrammed to enter an embryonic stem celllike state by being forced to express factors important for maintaining the "stemness" of embryonic stem cells (ESCs). Mouse iPSCs were first reported in 2006 (Takahashi and Yamanaka), and human iPSCs were first reported in late 2007 (Takahashi et al. and Yu et al.). Mouse iPSCs demonstrate important characteristics of pluripotent stem cells, including the expression of stem cell markers, the formation of tumors containing cells from all three germ layers, and the ability to contribute to many different tissues when injected into mouse embryos at a very early stage in development. Human iPSCs also express stem cell markers and are capable of generating cells characteristic of all three germ layers. Scientists are actively comparing iPSCs and ESCs to identify important similarities and differences.

In vitroLatin for "in glass"; in a laboratory dish or test tube; an artificial environment.

In vitro fertilizationA technique that unites the egg and sperm in a laboratory instead of inside the female body.

Inner cell mass (ICM)The cluster of cells inside the blastocyst. These cells give rise to the embryo and ultimately the fetus. The ICM cells are used to generate embryonic stem cells.

Long-term self-renewalThe ability of stem cells to replicate themselves by dividing into the same non-specialized cell type over long periods (many months to years) depending on the specific type of stem cell.

Mesenchymal stem cellsCells from the immature embryonic connective tissue. A number of cell types come from mesenchymal stem cells, including chondrocytes, which produce cartilage.

MeiosisThe type of cell division a diploid germ cell undergoes to produce gametes (sperm or eggs) that will carry half the normal chromosome number. This is to ensure that when fertilization occurs, the fertilized egg will carry the normal number of chromosomes rather than causing aneuploidy (an abnormal number of chromosomes).

MesodermMiddle layer of a group of cells derived from the inner cell mass of the blastocyst; it gives rise to bone, muscle, connective tissue, kidneys, and related structures.

MicroenvironmentThe molecules and compounds such as nutrients and growth factors in the fluid surrounding a cell in an organism or in the laboratory, which play an important role in determining the characteristics of the cell.

MitosisThe type of cell division that allows a population of cells to increase its numbers or to maintain its numbers. The number of chromosomes remains the same in this type of cell division.

MultipotentHaving the ability to develop into more than one cell type of the body. See also pluripotent and totipotent.

Neural stem cellA stem cell found in adult neural tissue that can give rise to neurons and glial (supporting) cells. Examples of glial cells include astrocytes and oligodendrocytes.

NeuronsNerve cells, the principal functional units of the nervous system. A neuron consists of a cell body and its processesan axon and one or more dendrites. Neurons transmit information to other neurons or cells by releasing neurotransmitters at synapses.

OligodendrocyteA supporting cell that provides insulation to nerve cells by forming a myelin sheath (a fatty layer) around axons.

ParthenogenesisThe artificial activation of an egg in the absence of a sperm; the egg begins to divide as if it has been fertilized.

PassageIn cell culture, the process in which cells are disassociated, washed, and seeded into new culture vessels after a round of cell growth and proliferation. The number of passages a line of cultured cells has gone through is an indication of its age and expected stability.

PluripotentHaving the ability to give rise to all of the various cell types of the body. Pluripotent cells cannot make extra-embryonic tissues such as the amnion, chorion, and other components of the placenta. Scientists demonstrate pluripotency by providing evidence of stable developmental potential, even after prolonged culture, to form derivatives of all three embryonic germ layers from the progeny of a single cell and to generate a teratoma after injection into an immunosuppressed mouse.

Polar BodyA polar body is a structure produced when an early egg cell, or oogonium, undergoes meiosis. In the first meiosis, the oogonium divides its chromosomes evenly between the two cells but divides its cytoplasm unequally. One cell retains most of the cytoplasm, while the other gets almost none, leaving it very small. This smaller cell is called the first polar body. The first polar body usually degenerates. The ovum, or larger cell, then divides again, producing a second polar body with half the amount of chromosomes but almost no cytoplasm. The second polar body splits off and remains adjacent to the large cell, or oocyte, until it (the second polar body) degenerates. Only one large functional oocyte, or egg, is produced at the end of meiosis.

PreimplantationWith regard to an embryo, preimplantation means that the embryo has not yet implanted in the wall of the uterus. Human embryonic stem cells are derived from preimplantation-stage embryos fertilized outside a woman's body (in vitro).

ProliferationExpansion of the number of cells by the continuous division of single cells into two identical daughter cells.

Regenerative medicineA field of medicine devoted to treatments in which stem cells are induced to differentiate into the specific cell type required to repair damaged or destroyed cell populations or tissues. (See also cell-based therapies).

Reproductive cloningThe process of using somatic cell nuclear transfer (SCNT) to produce a normal, full grown organism (e.g., animal) genetically identical to the organism (animal) that donated the somatic cell nucleus. In mammals, this would require implanting the resulting embryo in a uterus where it would undergo normal development to become a live independent being. The first animal to be created by reproductive cloning was Dolly the sheep, born at the Roslin Institute in Scotland in 1996. See also Somatic cell nuclear transfer (SCNT).

SignalsInternal and external factors that control changes in cell structure and function. They can be chemical or physical in nature.

Somatic cellany body cell other than gametes (egg or sperm); sometimes referred to as "adult" cells. See also Gamete.

Somatic cell nuclear transfer (SCNT)A technique that combines an enucleated egg and the nucleus of a somatic cell to make an embryo. SCNT can be used for therapeutic or reproductive purposes, but the initial stage that combines an enucleated egg and a somatic cell nucleus is the same. See also therapeutic cloning and reproductive cloning.

Somatic (adult) stem cellsA relatively rare undifferentiated cell found in many organs and differentiated tissues with a limited capacity for both self renewal (in the laboratory) and differentiation. Such cells vary in their differentiation capacity, but it is usually limited to cell types in the organ of origin. This is an active area of investigation.

Stem cellsCells with the ability to divide for indefinite periods in culture and to give rise to specialized cells.

Stromal cellsNon-blood cells derived from blood organs, such as bone marrow or fetal liver, which are capable of supporting growth of blood cells in vitro. Stromal cells that make the matrix within the bone marrow are also derived from mesenchymal stem cells.

SubculturingTransferring cultured cells, with or without dilution, from one culture vessel to another.

Surface markersProteins on the outside surface of a cell that are unique to certain cell types and that can be visualized using antibodies or other detection methods.

Teratoma A multi-layered benign tumor that grows from pluripotent cells injected into mice with a dysfunctional immune system. Scientists test whether they have established a human embryonic stem cell (hESC) line by injecting putative stem cells into such mice and verifying that the resulting teratomas contain cells derived from all three embryonic germ layers.

Therapeutic cloningThe process of using somatic cell nuclear transfer (SCNT) to produce cells that exactly match a patient. By combining a patient's somatic cell nucleus and an enucleated egg, a scientist may harvest embryonic stem cells from the resulting embryo that can be used to generate tissues that match a patient's body. This means the tissues created are unlikely to be rejected by the patient's immune system. See also Somatic cell nuclear transfer (SCNT).

TotipotentHaving the ability to give rise to all the cell types of the body plus all of the cell types that make up the extraembryonic tissues such as the placenta. (See also Pluripotent and Multipotent).

TransdifferentiationThe process by which stem cells from one tissue differentiate into cells of another tissue.

TrophectodermThe outer layer of the preimplantation embryo in mice. It contains trophoblast cells.

TrophoblastThe outer cell layer of the blastocyst. It is responsible for implantation and develops into the extraembryonic tissues, including the placenta, and controls the exchange of oxygen and metabolites between mother and embryo.

Umbilical cord blood stem cellsstem cells collected from the umbilical cord at birth that can produce all of the blood cells in the body (hematopoietic). Cord blood is currently used to treat patients who have undergone chemotherapy to destroy their bone marrow due to cancer or other blood-related disorders.

UndifferentiatedA cell that has not yet developed into a specialized cell type.

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Glossary [Stem Cell Information]

Approximately 12 million Americans suffer from a disease called dry eye syndrome. Dry eye syndrome is a chronic lack of sufficient lubrication and moisture in the eye. Its consequences range from subtle but consistent irritation to ocular inflammation of the anterior tissues of the eye. The condition is one of the most common disorders among people over 40. In fact, 20% of all adults have some degree of dry eye syndrome and women past menopause are especially susceptible.

For some people, the stinging, burning and redness may seem like little more than a nuisance. But, if left untreated, dry eye syndrome can lead to serious eye problems, including blindness. Dry eyes are inflamed eyes. Inflammation of the front surface of the eye increases the risk of infection and can also lead to scarring. Once scarring occurs, permanent loss of sight can occur.

Understanding Dry Eye Syndrome

Tears are essential for good eye health, bathing the eye, washing out dust and debris while keeping the eye moist. The eyes produce two types of tears lubricating and reflex tears. Lubricating tears are composed of three layers which coat the eye with mucus and contain water, proteins and oil to protect the eye and prevent evaporation of the aqueous layer. Reflex tears are produced in response to eye injury or irritation.

With dry eye syndrome, the eye does not produce enough tears or the tears have a chemical composition that causes them to evaporate too quickly. The cause of dry eye syndrome is a dysfunction of the tear-producing glands which results in reduced production of tears. It can occur as a part of the natural aging process, especially during menopause or as a side effect of many medications such as antihistamines, anti-depressants, diuretics, certain blood pressure medications, Parkinsons medication and birth control pills.

Dry eye syndrome can be aggravated if you live in a dry, dusty or windy climate. Air conditioning and dry heating systems can dry out your eyes as well. Insufficient blinking, such as when you are staring at a computer screen all day can contribute to it as well.

Recent research indicates that contact lens wear and dry eyes can be a vicious cycle. Dry eyes are the most common complaint among contact lens wearers. Dry eye syndrome results in contact lens discomfort and the rubbing of the lens against the conjunctiva seem to be a cause of dry eyes.

Dry eye syndrome is common in women, possibly due to hormonal fluctuations. Recent research suggests that smoking, too, can increase your risk of dry eye syndrome.

Dry eyes are also a symptom of systemic diseases such as lupus, rheumatoid arthritis, Rosacea or Sjorgrens syndrome.

Signs and Symptoms of Dry Eye Syndrome

Persistent dryness, scratching and burning in your eyes are signs of dry eye syndrome. These symptoms alone may be enough to diagnose dry eye syndrome. Sometimes, the amount of tears in your eyes is measured, using a Schirmer test. This is done by placing a thin strip of filter paper at the edge of the eye. Some people also experience a foreign body sensation the feeling that something is in the eye.

Center For Sight is a leader in bringing our patients the latest advances for the care of dry eye syndrome. Today, there are more treatment options than ever that can help to reduce or eliminate the symptoms, depending on the dryness of your eyes.

Artificial Tears

The simplest approach to treating dry eyes is to supplement your bodys natural tears with lubricating artificial tears. We recommend using mildly preserved brands such as Tears Plus, Refresh, Systane, Soothe or their preservative free counterparts, as well as Bion Tears or TheraTears.

Nutritional Supplementation

Studies have shown that Vitamin A deficiency is linked to dry eye syndrome. Your doctor might suggest a specific formulation, such as TheraTears Nutrition or BioTears.

Medications

Dry eye syndrome has been shown to be an inflammatory eye disorder and your doctor might prescribe anti-inflammatory medicines such as Restasis (eye drops used twice daily) or Lotemax (your doctor will prescribe the frequency of use).

Environmental Control

You may be able to significantly ease the discomfort of dry eye syndrome by reducing factors in your environment that contribute to the problem. Maintaining humidity, avoiding the use of ceiling fans and looking away from the computer or television screen every ten minutes are all helpful. Also, try to blink more frequently to spread tears over the eyes.

Tear Duct Inserts

The eyes lubricating balance is maintained by its volume and quality of tears produced by certain glands, and excess tears are drained into the nose and throat through tear ducts located in each eyelid. If the drain is working too well, the eyes natural moisture can be lost, resulting in a dry eye. Your doctor might elect to insert a temporary (collagen) or permanent (silicone or thermoacrylic) stopper to plug the drainage, allowing your own tears to bathe your eyes for a longer period. They are inserted in a painless in-office procedure and may be removed at any time.

Make the Clear Choice

Our physicians examine and treat eye disorders and diseases and coordinate all post-operative care. They provide 24 hour/7 days a week emergency care to all our patients.

Click here to request an appointment with a Center For Sight optometric physician or call the location nearest to you.

University Park 351-9440 Sarasota US 41 925-2020 Sarasota Siesta Dr. 953-2020 Sarasota - Fruitville 923-4594 Venice 488-2020 Englewood 474-2020 North Port 484-2020

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Dry Eye and Dry Eye Syndrome - Center for Sight in ...

Botanical Stem Cell Nutrition

Stem cell nutrition from aqua-botanical source, has shown to support the release of millions of adult stem cells from the bone marrow very quickly. These stem cells can then migrate and attach to any cells, tissue, bone, muscle, cartilage, organ anywhere in the body needing repair. Once they attach, they become that tissue and multiply 3 to 5000 times.

When there is an injury or a stress to an organ, compounds are released that reach the bone marrow and trigger the release of stem cells. Stem Cells can be thought of as master cells. Stem cells circulate and function to replace dysfunctional cells, thus fulfilling the natural process of maintaining optimal health

When Christian Drapeau first posited that Adult Stem Cells were the very foundation of the body's natural healing system, scientific study in the field was in its infancy. His hypothesis that Adult Stem Cells, created by bone marrow, flowed to any tissue or organ needing regeneration and morphed into healthy cells of that location, was initially ridiculed by medical science. Since 2006 however, and at a geometrically increasing pace, Christian Drapeau's position gained not just momentum but widespread interest in scientific circles as study after study reveals that Adult Stem Cell science holds phenomenal promise in all areas of human healing.

Stem cell nutrition are typically aquatic botanicals and support wellness by assisting the body in its ability to maintain healthy stem cell physiology, production, and placement. Just as antioxidants are important to protect your cells from free radical damage, stem cell nutrition is equally important to support your stem cells in maintaining proper organ and tissue functioning in your body.

The health benefits of having more stem cells in the blood circulation have been demonstrated by numerous scientific studies. It would be too long here to summarize this vast body of scientific data. I simply suggest you research the work of Dr. Donald Orlic at the NIH.

Christian's theory that Adult Stem Cells are nothing less than the human body's natural self-renewal system has profound implications for every area of modern medicine. The idea that heart disease, diabetes, liver degeneration, and other conditions could be things of the past is no longer science fiction; because of recent Adult Stem Cell research breakthroughs, these are real possibilities in the short term.

Stem cells are defined as cells with the unique capacity to self-replicate throughout the entire life of an organism and to differentiate into cells of various tissues. Most cells of the body are specialized and play a well-defined role in the body. For example, brain cells respond to electrical signals from other brain cells and release neurotransmitters; cells of the retina are activated by light, and pancreatic -cells produce insulin. These cells, called somatic cells, will never differentiate into other types of cells or even proliferate. By contrast, stem cells are primitive cells that remain undifferentiated until they receive a signal prompting them to become various types of specialized cells.

Botanical stem cell nutrition are available in countries around the world.

The Stem Cell Theory of Renewal proposes that stem cells are naturally released by the bone marrow and travel via the bloodstream toward tissues to promote the body's natural process of renewal. When an organ is subjected to a process that requires renewal, such as the natural aging process, this organ releases compounds that trigger the release of stem cells from the bone marrow. The organ also releases compounds that attracts stem cells to this organ. The released stem cells then follow the concentration gradient of these compounds and leave the blood circulation to migrate to the organ where they proliferate and differentiate into cells of this organ, supporting the natural process of renewal.

Most of the cells in the human body are specialists assigned to a specific organ or type of tissue, such as the neuronal cells that wire the brain and central nervous system. Stem cells are different. When they divide, they can produce either more stem cells, or they can serve as progenitors that differentiate into specialized cells as they mature. Hence the name, because specialist cells can "stem" from them. The potential to differentiate into specialist cells whose populations in the body have become critically depleted as the result of illness or injury is what makes stem cells so potentially valuable to medical research.

The idea is that if the fate of a batch of stem cells could be directed down specific pathways, they could be grown, harvested, and then transplanted into a problem area. If all went according to plan, these new cells would overcome damaged or diseased cells, leading to healing and recovery. "The life of a stem cell can be viewed as a hierarchical branching process, where the cell is faced with a series of fate switches," Schaffer says. "Our goal is to identify the cell fate switches, and then provide stem cells with the proper signals to guide them down a particular developmental trajectory."

Stem cells have the remarkable potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

When a stem cell divides, each new cell has the potential to either remain a stem cell or become another type of cell with a more specialized function. Scientists believe it should be possible to harness this ability to turn stem cells into a super "repair kit" for the body.

Scientist and author Christian Drapeau explains how the Stem Cell enhancers function to maximize human performance - Supporting the release of stem cells from the bone marrow and increasing the number of circulating stem cells improves various aspects of human health. For very active and sports focused people, Stem Cells are the raw materials to repair micro-tears and micro-injuries created during training. The results, according to Drapeau, are that active people, whether former NBA stars or amateur weekenders, can exercise more intensely at each training session with the ultimate consequence of greater performance.

Theoretically, it should be possible to use stem cells to generate healthy tissue to replace that either damaged by trauma, or compromised by disease. Among the conditions which scientists believe may eventually be treated by stem cell therapy are Parkinson's disease, Alzheimer's disease, heart disease, stroke, arthritis, diabetes, burns and spinal cord damage.

Do you have a question about holistic health or need assistance? Email Shirley Call 323-522-4521

Aquatic plant-based stem cell nutrition have been shown to support the release of millions of stem cells from the bone marrow very quickly. These stem cells can then migrate and attach to any cells, tissue, bone, muscle, cartilage, organ anywhere in the body needing repair. Once they attach, they become that tissue and multiply 3 to 5000 times. When there is an injury or a stress to an organ of your beloved pet or horse, compounds are released that reach the bone marrow and trigger the release of stem cells. Stem Cells can be thought of as master cells. Stem cells circulate and function to replace dysfunctional cells, thus fulfilling the natural process of maintaining optimal health.

As they do in humans, adult stem cells reside in animals bone marrow, where they are released whenever there is a problem somewhere in the body. Looking back on stem cell research, we realize that most studies have been done with animals, mostly mice, but also with dogs, horses, pigs, sheep and cattle. These studies have revealed that animal stem cells conduct themselves the same way human stem cells do. When there is an injury or a stress to an organ of your beloved pet or horse, compounds are released that reach the bone marrow and trigger the release of stem cells. The stem cells then travel to tissues and organs in need of help to regain optimal health.

Eve-Marie Lucerne - Eve-Marie keeps nine horses, all older thoroughbreds, and was eager to participate in the trials of a new stem cell enhancer for horses. She shared her allotment of test products with a few large commercial thoroughbred farms, veterinarians and other horse people she knows, and has been pleased with the consistently excellent results she has seen and others have reported to her. This product will help so many animals, she says, adding, People and animals are more alike than we are different. So it makes sense that a stem cell enhancer for animals with promote their health, too.

Eve-Marie's Equine Stem Cells Nutrition show dramatic results. For several horses facing serious physical challenges, cases where the animals might have to be put down, we saw a return to quality of life. This did not happen before Equine Stem Cell Nutrition. Eve-Marie says that this turnaround was quick, less than two weeks in many cases, and that the subject horses were back to health and enjoying pasture life within a month. One of the unofficial trial subjects for the equine stem cell nutrition was a 30-year old donkey who was in bad shape, Eve-Marie reports. He hadchronic respiratory difficulty and could move about only haltingly. His owner had stem cell enhancer supplements to help with her own serious health challenges and shared it with the donkey. The donkey's owner says this is the first time she wasn't sick, and her donkey is walking all around, feeling great an enjoying life again!

Farrier and National Hoof practitioner Stephen Dick received some of the trial product from Eve-Marie, and had good results with the two horses he selected for trial. For a 12-year-old quarterhorse stallion, the equine product brought dramatic results. This horse used to lie down twenty-two hours of the day, because he suffered discomfort whenever he stood, Steve reports, continuing, after a couple of weeks with Equine Stem Cell Nutrition, he was getting up and moving around, showing no discomfort. For a high-spirited mare with a leg problem, the equine product brought about a whole new lease on life, Steve says. This horse had been in a stall for 8 months. After about 6 weeks taking the equine product with her grain, her condition had improved and she was out of the stall, walking around in the pasture again.

Little Joe, a small 18-year-old quarterhorse that Judy Fisher bought when he was nearly 400 pounds underweight. You could count his ribs, Judy says, remembering, and his backbone stuck up like a ridge all along his back. He was very, very thin! Little Joe also suffered from breathing problems that kept him lethargic and inactive. Vet-recommended remedies were unsuccessful in changing Little Joe's physical problems, and the vet told Judy he didn't expect Little Joe to live through the winter. I figured Little Joe was in such bad shape that anything was worth a try, she says. She began giving the horse stem cell nutrition with his feed and grain twice a day. Within a couple of weeks, Judy was surprised to see Little Joe beginning to gain weight and run, buck, snort and kick. His breathing was no longer labored and his skin and coat were improving. Within six weeks Little Joe's overall appearance had changed dramatically. He had put on almost 300 pounds. When his former owner came to visit, Judy says, he didn't recognize Little Joe. That's how different he looked!

Sara participated in the stem cell nutrition product trials with her two horses and her 80-pound mixed-breed dog. She noted significant improvement in the health and quality of life for all three animals during the time of the trials. For JJ, Sara's 18-year old quarterhorse, the equine product brought about improvements in his overall mood, appearance and alertness quickly. He really liked the product from the beginning, Sara reports, pointing out that Hank, her 16-year-old thoroughbred/quarterhorse, had not taken to the taste of it too readily. I was able to slowly wean him on it though, she says. For Hank, the equine product was a balm for the skin problems resulting from his allergy to fly bites. His skin condition improved dramatically. Sara reports, noting that before the equine product the horse had scratched and bitten himself into ope wounds; after the equine product, the scratching and biting dropped off to almost nothing. Sara also noticed an increase in Hank's energy and liveliness in the first week on the equine product. The horse's foot and hip discomforts also responded well, leading to a noticeable increase in his mobility and an overall improvement in his quality of life throughout the two-month study.

Sara gave the pet product to her dog, Roxy, who had suffered for two years with ear problems that led to scratching, often until her skin was raw. Vet-recommended remedies had been temporary, quick-fixes, Sara says, but the discomfort always returned with a vengeance. For the pet trials, Sara gave Roxy two tabs of the product a day for two months, noting this is the only supplement she was getting. Sara says Roxy's problem with her ears definitely improved, the hair as grown back on her head and ears, and the ear problem has not recurred, adding that Roxy is happier and engaging, more playful.

Sonya had originally planned to use only her six-year-old Doberman Pinscher, Ginger, as a test subject for the pet product to see if the product could help with discomfort in her hips that had limited her mobility. That was until the day when Sonya's 14-year-old Irish Setter/Lab, Rowdy, took it upon himself to scarf up some large crumbs from Ginger's test dose of the pet product. Before dining on Ginger's leftovers, Rowdy was best characterized as the lazy dog type, very lethargic and he never left my side, Sonya reports.

Using the nutritional stem cell pet product , the first day Rowdy found the puppy back to his old self again, says Sonya and wanted to stay out all night, tracking who-knows-what, but having a great time. Sonya added Rowdy to her trial regimen and says that only two-three trial chewables made the difference in Rowdy's energy level, returning him to youthful activity. Meanwhile, the original trial subject, Ginger, has a new life and is able to keep up with 2-year-old Norwich Terrier mix Scrappy for the first time ever. Ginger has regained her ability to run at top speeds, and is able to dig for hours with Scrappy. Previously unable to get up from a prone position without some difficulty, Ginger now leaps to standing or chasing positions without a moment's hesitation. Stem Cell Nutrition for dogs has helped both of my big dogs to have their youth back, Sonya reports, adding I am a real believer in the canine product, as it has provided a spectacular change in both Ginger and Rowdy.

For dogs, depending on the size of your companion, you simply give half or one full tablet, which has a tasty dried beef and liver meal flavor. For horses, to the animal's daily grain you add one scoop of scrumptious molasses based Stem Cell Enhancer.

My German Shepherd was not able to get around, but within 2 weeks of using Stem Cell Nutrition for pets, her hips were not as stiff and she started running like a puppy. Jan, IN

Both of my big dogs have gained their youth back. I am a true believer in Stem Cell Nutrition for pets as it has provided a spectacular change in both Ginger and Rowdy. Sonya, IN

Stem cell nutrition for dogs, horses and other animals are specially formulated to be a delectable treat for your animal. The pet chewables and equine blends make it easy to provide your animals with this valuable nutritional supplement. The most common story is that of old, tired and sluggish dogs turned within a week or so into active, alert dogs running around like puppies. The same was observed in horses. Old horses who used to remain standing in the barn or under a tree, sluggish or stricken by too much discomfort to walk around, suddenly began moving about, and at times running and bucking like young colts. One of the most common reports was obvious improvements in hoof health and coat appearance.

Botanical stem cell nutrition are available in countries around the world.

Frequently Asked Questions about Stem Cell Enhancer Bibliography

Do you have a question about holistic health or need assistance? Email Shirley Call 323-522-4521

The National Health Institute lists seventy-four treatable diseases using ASCs in therapy - an invasive and costly procedure of removing the stem cells from one's bone marrow (or a donor's bone marrow) and re-injecting these same cells into an area undergoing treatment. For example, this procedure is sometimes done before a cancer patient undergoes radiation. Healthy stem cells from the bone marrow are removed and stored, only to be re-inserted after radiation into the area of the body in need of repair. This is a complex and expensive procedure, not accessible to the average person. However, there is now a way that every single person, no matter what their health condition, can have access to the benefits of naturally supporting their body's innate ability to repair every organ and tissue using stem cell nutrition.

David A. Prentice, Ph.D. - "Within just a few years, the possibility that the human body contains cells that can repair and regenerate damaged and diseased tissue has gone from an unlikely proposition to a virtual certainty. Adult stem cells have been isolated from numerous adult tissues, umbilical cord, and other non-embryonic sources, and have demonstrated a surprising ability for transformation into other tissue and cell types and for repair of damaged tissues.

A new U.S. study involving mice suggests the brain's own stem cells may have the ability to restore memory after an injury. These neural stem cells work by protecting existing cells and promoting neuronal connections. In their experiments, a team at the University of California, Irvine,were able to bring the rodents' memory back to healthy levels up to three months after treatment. The finding could open new doors for treatment of brain injury, stroke and dementia, experts say.

"This is one of the first reports that you can take a stem cell transplantation approach and restore memory," said lead researcher Mathew Blurton-Jones, a postdoctorate fellow at the university. "There is a lot of awareness that stem cells might be useful in treating diseases that cause loss of motor function, but this study shows that they might benefit memory in stroke or traumatic brain injury, and potentially Alzheimer's disease."

In the study, published in the Oct. 31 issue of the Journal of Neuroscience, Blurton-Jones and his colleagues used genetically engineered mice that naturally develop brain lesions. The researchers destroyed cells in a brain area called the hippocampus. These cells are known to be vital to memory formation and it is in this region that neurons often die after injury, the researchers explained. To test the mice's memory, Blurton-Jones's group conducted place and object recognition tests with both healthy mice and brain-injured mice.

Healthy mice remembered their surroundings about 70 percent of the time, while brain-injured mice remembered it only 40 percent of the time. For objects, healthy mice recalled objects about 80 percent of the time, but injured mice remembered them only 65 percent of the time. The researchers then injected each mouse with about 200,000 neural stem cells. They found that mice with brain injuries that received the stem cells now remembered their surroundings about 70 percent of the time -- the same as healthy mice. However, mice that didn't receive stem cells still had memory deficits.

The researchers also found that in healthy mice injected with stem cells, the stem cells traveled throughout the brain. In contrast, stem cells given to injured mice lingered in the hippocampus. Only about 4 percent of those stem cells became neurons, indicating that the stem cells were repairing existing cells to improve memory, rather than replacing the dead brain cells, Blurton-Jones's team noted. The researchers are presently doing another study with mice stricken with Alzheimer's. "The initial results are promising," Blurton-Jones said. "This has a huge potential, but we have to be cautious about not rushing into the clinic too early."

One expert is optimistic about the findings. "Putting in these stem cells could eventually help in age-related memory decline," said Dr. Paul R. Sanberg, director of the Center of Excellence for Aging and Brain Repair at the University of South Florida College of Medicine. "There is clearly a therapeutic potential to this." Sanberg noted that for the process to work with Alzheimer's it has to work with older brains. "There is clearly therapeutic potential in humans, but there are a lot of hurdles to overcome," he said. "This is another demonstration of the potential for neural stem cells in brain disorders.".

Botanical stem cell nutrition are available in countries around the world. (Select market/country at the top)

Dr. Nancy White Ph.D.- " I've always been interested in health generally and in particular the brain, focusing on the balance of neurotransmitters. I often do quantitative EEG's for assessment of my patients. I'm impressed with the concept of a natural product like stem cell nutrition that could help release adult stem cells from the bone mass where the body would have no objection and no rejection. I've tried stem cell nutrition for general health anti-aging. After taking it for a time, I fell more agile and my joints are far more flexible. I was astounded while doing yoga that I was suddenly able to bend over and touch my forehead to my knees. I haven't been able to do that comfortably in probably twenty years. I noticed how much better my balance has become. I believe stem cell nutrition is responsible for these effects, because I certainly haven't been trained extensively in yoga. Also since taking stem cell nutrition, I feel better and my skin is more moist and has a finer texture.

A bald friend of mine, who is also taking the stem cell nutrition, had several small cancers on top of his head. His doctor had removed one from his arm already, and his dermatologist set a date to remove those from his scalp. Before the appointment, my friend was shaving one morning and, looking in the mirror, saw that the cancers were all gone. They had disappeared within a few weeks of starting the stem cell nutrition and his skin is better overall. Also, his knee, which he'd strained playing tennis, was like new. Stem cell nutrition seems to go where the body's priority is. You never know what the affect is going to be, but you notice something is changing. Another friend of mine seems to be dropping years. Her skin looks smoother and her face younger. After about six weeks on the stem cell nutrition, she looks like she's ten years younger. A woman who gives her regular facials asked what she was doing, because her skin looked so much different. Stem cell nutrition is remarkable and could help anybody. Everybody should try it, because it's natural and there are no risks. As we grow older in years, we still can have good health. That's the ideal. Even if you don't currently have a problem, stem cell nutrition is a preventative." Dr. White holds a Ph. D. in Clinical Psychology, an MA in Behavioral Science, and a B.F.A. in Fine Arts, Magna Cum Laude. In addition, she is licensed in the State of Texas as a Psychologist , a Marriage and Family Therapist and as a Chemical Dependency Counselor.

Dr. Cliff Minter - "Stem cells are the most powerful cells in the body. We know that stem cells, once they're circulating in the bloodstream, will travel to any area of the body that has been compromised or damaged and turn into healthy cells. There have been controversial discussions about the new stem cells found in embryos, but the truth is that everyone has adult stem cells in their own bodies. We are all created from stem cells. As a child or a young adult, your body automatically releases stem cells whenever you injure yourself. That's why you heal so fast when you are younger. After about age 35, we don't heal as fast anymore, because the stem cells aren't released the same way as when we are younger. Stem cell nutrition helps all of us heal our bodies. If you look at the New England Journal of Medicine, you'll find that the number one indicator of a healthy heart is the number of stem cells circulating in the body. Stem cell nutrition is the organic and all-natural way to stimulate the bone marrow to release adult stem cells into the bloodstream.

By taking stem cell nutrition, you can maintain optimum health and aid your body in healing itself. It's certainly a better way to recuperate from an illness than using prescription drugs, because even when a medication works, it can often be hard on your liver and the rest of your body. Stem cell nutrition has no negative side effects. This makes it a powerful approach to healing and good health in general. I found out about stem cell nutrition after someone asked for my opinion on it. I did some research and found it to be one of the greatest ways to slow down aging that we have. Aging is nothing more than the breakdown of cells. Stem cell nutrition combats that action. As cells break down, stem cell nutrition replaces them with healthy cells. This is the greatest, most natural anti-aging method I know. I was skeptical at first, but the results I've personally seen in people I've talked with have been wide-ranged. Lots of people have reported an increase in energy and better sleeping patterns.

I've seen people with arthritis in various parts of their bodies reverse the disease, and people with asthma end up with their lungs totally clear. One person that was on oxygen almost 24/7 is now totally off of oxygen. Two ladies who suffered badly from PMS told me they were 100 percent symptom-free within weeks of starting the stem cell nutrition. Two people I know had tennis elbow which usually takes about six to nine months to heal. Within weeks of taking stem cell nutrition, both report their "tennis elbow" is gone. It makes sense, because stem cells go to whatever area is compromised and turn into healthy cells.

I use stem cell nutrition as a preventative. I've noticed an increase in my energy level and an improved sleeping pattern. Stem cell nutrition has zero negative side effects, is very powerful, and we know how it works. It's good for children as well as adults. This is the best, most natural way I know to optimum health. If you just want to use it for prevention, this is the best thing I know for staying healthy. And if you do those and regaining optimum health. I recommend it to everybody." Dr. Cliff Minter (retired) graduated from Illinois College of Podiatric Medicine. He completed his residency at the Hugar Surgery Center in the Hines Veteran Administration Hospital in Illinois before going into private practice in Ventura, CA. Dr. Minter is a national and international speaker on the subjects of business and nutritional products.

Fernando Aguila, M.D. - "Due to a heavy patient load, I have recently found that I tire more easily, my legs are cramping, and by the time I get home, even my shoulders and rib cage hurt. I knew I had to find a way to increase my stamina, energy and vitality. A friend gave me information about stem cell nutrition and how it promotes the release of stem cells in the body. One of the components apparently promotes the migration of the stem cells to tissues or organs where regeneration and repair is needed most. My attention was drawn to the fact that it can increase energy, vitality, wellness, concentration, and much more. It sounded just like what I needed. Since then, I've heard reports of people experiencing excellent results in a number of different areas in their health. The improvements sounded dramatic. Because of all of their testimonies, I was willing to believe it could promote wellness in the human body.

I tried stem cell nutrition myself. After a day, of hard work, I realized I wasn't tired at all, my legs were not aching, and I didn't have any shoulder pain. I decided the stem cell nutrition must be working. I continued to take it, and was able to work so efficiently and steadily that one surgeon commented that I was moving like a ball of fire. Stem cell nutrition gives me support physically and mentally. I look forward to seeing what the major medical journals have to say about the studies being done with this new approach to wellness." Fernando Aguila, M.D., graduated from the University of Santa Thomas in Manila , Philippines. He finished his internship at Cambridge City Hospital, Cambridge, MA and completed his residency at the New England Medical Center in Boston, MA. He obtained a fellowship in OB-GYN anesthesia at the Brigham and Women's Hospital in Boston and a fellowship in cardio-thoracic anesthesia at the Cleveland Clinic Foundation in Cleveland, OH.

Botanical stem cell nutrition are available in countries around the world

View Dr. Christian Drapeau's introduction to Adult Stem Cell Bone Marrow Release

Christian Drapeau is America's best known advocate for Adult Stem Cell science health applications and the founder of the field of Stem Cell Nutrition. He holds a BS in Neurophysiology from McGill University and a Master of Science in Neurology and Neurosurgery from the Montreal Neurological Institute.

One particular stem cell enhancers that was studied was found to contain a polysaccharide fraction that was shown to stimulate the migration of Natural Killer (NK) cells out of the blood into tissues. The same polysaccharide fraction was also shown to strongly stimulate the activation of NK cells. NK cells play the very important role in the body of identifying aberrant or defective cells and eliminating them. NK cells are especially known for their ability to detect and destroy virally infected cells and cells undergoing uncontrolled cellular division. The same polysaccharide fraction was also shown to stimulate macrophage activity. Macrophages constitute the front line of the immune system. They first detect an infection or the presence of bacteria or virally infected cells, and they then call for a full immune response. Adult Stem Cell Nutritional Enhancer also contains a significant concentration of chlorophyll and phycocyanin, the blue pigment in AFA. Phycocyanin has strong anti-inflammatory properties and therefore can assist the immune system.

The release of stem cells from the bone marrow and their migration to tissues is a natural process that happens everyday. Stem cell enhancers simply support that natural process and tips the balance toward health everyday. It does not do anything that the body does not already do everyday. So far, no instances of cancer or any similar problem have ever been observed when using in vivo natural release of stem cells from the bone marrow.

Each day, stem cells in the bone marrow evolve to produce red blood cells, white blood cells, and platelets. These mature cells are then released into the bloodstream where they perform their vital life-supporting functions. When bone marrow stem cell activity is interfered with, diseases such as anemia (red blood cell deficit), neutropenia (specialized white blood cell deficit), or thrombocytopenia (platelet deficit) are often diagnosed. Any one of these conditions can cause death if not corrected.

Scientists have long known that folic acid, vitamin B12, and iron are required for bone marrow stem cells to differentiate into mature red blood cells.3-7 Vitamin D has been shown to be crucial in the formation of immune cells,8-11 whereas carnosine has demonstrated a remarkable ability to rejuvenate cells approaching senescence and extend cellular life span.12-28

Other studies of foods such as blueberries show this fruit can prevent and even reverse cell functions that decline as a result of normal aging.29-36 Blueberry extract has been shown to increase neurogenesis in the aged rat brain.37,38 Green tea compounds have been shown to inhibit the growth of tumor cells, while possibly providing protection against normal cellular aging.39,40

Based on these findings, scientists are now speculating that certain nutrients could play important roles in maintaining the healthy renewal of replacement stem cells in the brain, blood, and other tissues. It may be possible, according to these scientists, to use certain nutrient combinations in the treatment of conditions that warrant stem cell replacement

These studies demonstrate for the first time that various natural compounds can promote the proliferation of human bone marrow cells and human stem cells. While these studies were done in vitro, they provide evidence that readily available nutrients may confer a protective effect against today's epidemic of age-related bone marrow degeneration.

Dr. Robert Sampson, MD on stem cell nutrition - "... we have a product that has been shown and demonstrated in the patent to increase the level of adult circulating stem cells by up to 30%. It seems to me we're having a great opportunity here to optimize the body's natural ability to create health." Recent scientific developments have revealed that stem cells derived from the bone marrow, travel throughout the body, and act to support optimal organ and tissue function. Stem cell enhancers supports the natural role of adult stem cells. Stem cell enhancer are typically derived from certain edible algae that grows in fresh water.

Botanical stem cell nutrition are available in countries around the world. (Select market/country at the top)

Do you have a question about holistic health or need assistance? Email Shirley Call 323-522-4521

The possibility that a decline in the numbers or plasticity of stem cell populations contributes to aging and age-related disease is suggested by recent findings. The remarkable plasticity of stem cells suggests that endogenous or transplanted stem cells can be tweaked' in ways that will allow them to replace lost or dysfunctional cell populations in diseases ranging from neurodegenerative and hematopoietic disorders to diabetes and cardiovascular disease.

As you age, the number and quality of stem cells that circulate in your body gradually decrease, leaving your body more susceptible to injury and other age-related health challenges. Just as antioxidants are important to protect your cells from free radical damage, stem cell nutrition is equally important to support your stem cells in maintaining proper organ and tissue functioning in your body.

A fundamental breakthrough in our understanding of nervous system development was the identification of multipotent neural stem cells (neurospheres) about ten years ago. Dr. Weiss and colleagues showed that EGF (epidermal growth factor) dependent stem cells could be harvested from different brain regions at different developmental stages and that these could be maintained over multiple passages in vitro. This initial finding has lead to an explosion of research on stem cells, their role in normal development and their potential therapeutic uses. Many investigators have entered this field and the progress made has been astounding.

How does an increase in the number of circulating stem cells lead to optimal health? Circulating stem cells can reach various organs and become cells of that organ, helping such organ regain and maintain optimal health. Recent studies have suggested that the number of circulating stem cells is a key factor; the higher the number of circulating stem cells the greater is the ability of the body at healing itself. Scientific interest in adult stem cells has centered on their ability to divide or self-renew indefinitely, and generate all the cell types of the organ from which they originate, potentially regenerating the entire organ from a few cells. Adult stem cells are already being used clinically to treat many diseases. These include as reparative treatments with various cancers, autoimmune disease such as multiple sclerosis, lupus and arthritis, anemias including sickle cells anemia and immunodeficiencies. Adult stem cells are also being used to treat patients by formation of cartilage, growing new corneas to restore sight to blind patients, treatments for stroke, and several groups are using adult stem cells to repair damage after heart attacks. Early clinical trials have shown initial success in patient treatments for Parkinsons disease and spinal cord injury. The first FDA approved trial to treat juvenile diabetes in human patients is ready to begin at Harvard Medical School, using adult stem cells. An advantage of using adult stem cells is that in most cases, the patients own stem cells can be used for the treatment, circumventing the problems of immune rejection, and without tumor formation.

Why do we hear much in the news about embryonic stem cells and very little about adult stem cells? The first human embryonic stem cells were grown in vitro, in a petri dish, in the mid 1990s. Rapidly, scientists were successful at growing them for many generations and to trigger their differentiation into virtually any kind of cells, i.e. brain cells, heart cells, liver cells, bone cells, pancreatic cells, etc. When scientists tried growing adult stem cells, the endeavor was met with less success, as adult stem cells were difficult to grow in vitro for more than a few generations. This led to the idea that embryonic stem cells have more potential than adult stem cells. In addition, the ethical concerns linked to the use of embryonic stem cells have led to a disproportionate representation of embryonic stem cells in the media. But recent developments over the past 2-3 years have established that adult stem cells have capabilities comparable to embryonic stem cells in the human body, not in the test tube. Many studies have indicated that simply releasing stem cells from the bone marrow can help support the body's natural process for renewal of tissues and organs.

The bone marrow constantly produces stem cells for the entire life of an individual. Stem cells released by the bone marrow are responsible for the constant renewal of red blood cells and lymphocytes (immune cells). A 25-30% increase in the number of circulating stem cells is well within physiological range and does not constitute stress on the bone marrow environment. The amount of active bone marrow amounts to about 2,600 g (5.7 lbs), with about 1.5 trillion marrow cells. Stem cells that do not reach any tissue or become blood cells return to the bone marrow.

Effectiveness of stem cell "enhancers" was demonstrated in a triple-blind study. Volunteers rested for one hour before establishing baseline levels. After the first blood samples, volunteers were given stem cell "enhancers"or placebo. Thereafter, blood samples were taken at 30, 60 and 120 minutes after taking the consumables. The number of circulating stem cells was quantified by analyzing the blood samples using Fluorescence-Activated Cell Sorting (FACS). Consumption of stem cell "enhancers" triggered a significant 25-30% increase in the number of circulating stem cells.

Botanical stem cell nutrition are available in countries around the world. (Select market/country at the top)

Do you have a question about holistic health or need assistance? Email Shirley Call 323-522-4521

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Adult Stem Cells Nutrition Boost Healing in Humans, Animals

Red Green Color Blindness

Red Green Color blindness is predominantly found only in men. The gene that leads to red green color blindness is found in the X Chromosome. Males only have one X chromosome whereas females have 2; typically in females the stronger chromosome takes precedence so theyretain correctvision.The son of a woman carrying a faulty gene has a 50% chance of inheriting the faulty X chromosome and as a result suffering from color blindness. The daughter of the same woman is unlikely to be color blind unless her father is color blind; however she retains a 50% chance of being a carrier for the defective gene.

Blue color blindness (often referredto as blue yellow color blindness) is extremely rare, so rare that only 5% of color blind people suffer from it.Unlike red green color blindness, the chance of having blue color blindness is equal in both men and women as the gene is found on a different chromosome ( chromosome 7). This gene is shared equally by men and women and blue color blindness comes from a mutation of this gene.

One might expect the percentage of affected people to be relatively constant in all countries however this is far from the truth. In most Caucasian societies up to 1 in 10 men suffer, however only 1 in 100 Eskimos are color blind. There is no solid proof as to the cause of this however it is logical to assume that less of the original Eskimos carried the defective gene, so the likelihood of it infecting the gene pool was quite a lot lower.

Whilst almost all color blindness is inherited, infrequently a change in the chromosome during early development can cause color blindness. Various injuries involving trauma to the eye, and even some diseases can also cause color blindness to develop in a person of any age.

As mentioned elsewhere on this website, cataracts are not a form of color blindness, so you wont see them in the table below. Cataracts are a clouding that develops in the crystalline lens of the eye, and have the effect to dull colors, and blur vision. It is not common to mistake someone with cataracts as someone who is color blind, as color blindness normally becomes apparent early in life, whereas cataracts dont usually form until ones senior years. However if you are unsure, you can take the freeonlinetests available on this website in the menu on the left to find out now.

The Below table displays the percentage of men and women suffering the different forms of color blindness, you can click on each defectto learn more about it.

Continued here:
Prevalence Color Blindness

Stem cells are unquestionably some of the most amazing cells in the human body. These are undifferentiated cells that do not have a direct blueprint or specific destiny. The can become differentiated into specialized cells anywhere throughout the body. They are classified as 2 different types of cells, those that are from embryonic origin and those called adult stem cells.

In the developing embryo, these cells differentiate into ectoderm, endoderm, and mesoderm. These give rise to our spine, nerves, and all our organs. Adult stem cells are primarily used to repair, replenish, and regenerate tissues.

Historically, stem cells can come from a variety of tissues. These include umbilical cord, fetal tissue, bone marrow, or the best source as adipose or fat cells.

Adipose derived stem cells have the highest numbers of cells when collected and tested compared to all others . This is by far the preferred method of stem cell therapy because of sheer numbers and the fact that they are coming from your own body. This is called autologous therapy.

Stem cell research in this country has been in existence for over 60 years. There are a wide range of studies and articles describing its dramatic benefit for chronic diseases. Many of these publications are available for you to read on my website.

In performing stem cell therapy, extremely strict guidelines mus be followed in coordination with a specialized clinical trial review board. This ensures accuracy, sterility, and quality control of the procedure. This information gathered from the procedure, including various forms of documentation can be used for medical publication at a later date. Physician notes and procedure as well as a questionnaire filled out by patients periodically are part of this process. This enables the highest level of procedure and documentation possible.

The procedure takes approximately one and a half hours to complete. Initially, patients are examined, appropriate blood or other testing is done and reviewed and schedule is made to begin procedure.

Typically, stem cell therapy is done within 2 weeks of initial consultation.

On the day of procedure, stem cells are extracted from abdominal belly fat, love handles, or around the buttocks, this takes 5-10 minutes then patients sit and relax while the processing is done. It is then washed and centrifuged 3 times to allow separation of cells and harvest stem cells. At the end of the procedure, microscopic analysis can estimate the number of stem cells available of injection. Injection can be done either into joint, connective tissue, muscle or for all other organs or systemic diseases, intravenously. Intranasal technique is also used for MS, Parkinsons and Alzheimers disease.

Diseases that are currently available for treatment with stem cells include:

Arthritis Alzheimers disease

COPD Critical Limb Ischemia

Diabetes Erectile Dysfunction

Frailty Syndrome Liver Failure

Localized Ischemia Lupus

Multiple Sclerosis Parkinsons Disease

Pulmonary Fibrosis Renal Failure

Rheumatoid Arthritis Stroke

Vascular Insufficiency Heart Failure

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Stem Cell Therapy / drcalapai.net

About | Treatment Options | Services

The Integrative Medicine Department is now a division of the Helen & Harry Gray Cancer Center. Acupuncture, ART for Healing, Guided Imagery, Massage Therapy and Reiki are offered hospital-wide to inpatients as well as outpatients at the Cancer Centers in Hartford and Avon, Outpatient Dialysis, and Post Operative Day Surgery.

Integrating Ancient Wisdom with High-Tech Medicine Recent surveys show that more than half of all Americans use some form of complementary or alternative therapy. Research has shown that techniques such as Acupuncture, ART for Healing, Guided Imagery, Massage Therapy, and Reiki help to decrease anxiety, strengthen the immune system, reduce pain and accelerate healing. These modalities and many more are available at Hartford Hospital.

Integrative Medicine at Hartford Hospital offers time proven relaxing and healing techniques along with the very latest medical technology!

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Recent surveys show that more than half of all Americans use some form of complementary or alternative therapy to enhance their healing or maintain their health.

Research has shown that relaxation techniques such as Acupuncture, ART for Healing, Guided Imagery, Imagery for Surgery, Massage Therapy, Therapeutic Touch, and Reiki help to decrease anxiety, strengthen the immune system, diminish pain, and accelerate healing.

While we often focus on the physical aspects of healing, we are learning that healing incorporates the mind, body, and spirit.

When mind-body techniques are used, benefits are often experienced on all three levels and there is often a greater sense of participating in the healing process.

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Why Choose Hartford Hospital? Since 1997 Hartford Hospital has been translating a new philosophy that integrates complementary therapies into Western medical practice to improve care and healing.

A Simple, Yet Strong Beginning Beginning with our Womens Health Services, which offers Reiki, Infant Massage, and Guided Imagery, the hospitals commitment to Integrative Medicine has grown rapidly. The Integrative Medicine Program was officially launched in1999 through a series of projects in Cardiology, Orthopedics, and Oncology by extending the Womens Health Services to patients, families and staff. Careful data collection measured overwhelming positive outcomes in pain reduction, anxiety relief, and patient satisfaction.

As we moved into a new millennium, we began offering community education programs to the public while our first Integrative Medicine Grand Rounds began to provide education to the medical community. In subsequent years ART For Healing, Acupuncture, Therapeutic Touch, Tai Chi and Yoga were added.

Education is Critical Building on the knowledge that education was key to the growth and success of this program, a special collection of books, audio and videotapes was added to the hospitals Medical Library. This collection is available for use by the public, hospital and affiliated staff.

A Bright Future The program recently celebrated its 7th anniversary and continues to grow and expand its services. The Integrative Medicine Department is committed to embracing the healthcare needs of Hartford Hospital as well as the community it serves.

Benefits of our Services

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Integrative Medicine | Hartford Hospital

Hip

" Hip injuries and replacements. "

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Patients with hip and knee issues experience severe and debilitating pain. On the other hand, patients can also expect a high rate of success with treatment. And new procedures like minimally-invasive surgery and computer-aided navigation show even greater promise and improved recovery times. Success is also contingent on a physician whose experience ensures these new techniques are applied effectively. You can be confident Lubbock Sports Medicines hip and knee specialists are not only current on the latest advancements, but come with the highest volume of surgical experience in the region. Patient Education Femoroacetabular Impingement (FAI) Hamstring Muscle Strain Hip Bursitis Hip Strains Muscle Strains in the Thigh Snapping Hip(IT Band Friction) Sports Hernia (Athletic Pubalgia) Treatments & Surgeries Activities After Hip Replacement Anesthesia for Hip and Knee Surgery Dislocation After Total Hip Replacement Hip Arthroscopy Hip Conditioning Program Hip Implants Hip Resurfacing Minimally Invasive Total Hip Replacement Total Hip Replacement Direct Anterior Hip Replacement Hip Physicians

" Arthritis, Sports Injuries, Surgeries, and more... "

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The back is a large, complex area of the body that contains muscles, bones, ligaments, tendons, nerves, and much more. More importantly, the back serves as home to the spinal column and has the responsibility of protecting it. Movement of the arms, hips, legs, and head can all be affected by an injury to the back. Few areas of the body are as complex, but our therapists have long been well-versed in the intricacies of the back. Though we don't normally see patients for back injuries (refer to a neurosurgeon specialist instead), our therapist are trained in innovate treatments that'll treat the whole body's motion and return you to top form! Patient Education & Treatments Low Back Pain Spondylolysis and Spondylolisthesis Back Pain in Children Osteoporosis and Spinal Fractures Herniated Disc Fractures in Thoracic or Lumber Spine Sciatica Perparing for Low Back Surgery Spine Conditioning Return to Play Protocol Low Back Pain Exercise Guide Visit lubbocksportsrehab.com or click the logo below for more information about setting up an appointment today! Back Therapists in Lubbock Mark A. O'Keefe Mark Caffey Kerry Wimberly Jon Murray DPT, PT, MS, CAFS PT, CAFS LAT, ATC, FAFS LAT, ATC, FAFS

" Arthritis, Sports Injuries, Surgeries, and more... "

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The shoulder is another complex joint of the body. It allows for a full range of motion including circular, anterior (pushing), posterior (pulling), and lateral movements. The large range of motion also increases its likelihood of suffering complications or injuries. The deepest layer of the shoulder is the bone and joint, with the next layer comprising of ligaments and the outermost layer of muscles and tendons. When you experience pain in the shoulder, it hinders your simple, daily activities and large portion of your active movements. Our physicians and clinicians carry special knowledge about the shoulder and with that extensive experience, we will achieve the best result for each patient, including innovative and progressive procedures exclusively offered to you from Lubbock Sports Medicine. Patient Education Biceps Tendon Tear at the Shoulder Burners and Stingers Chronic Shoulder Instability Common Shoulder Injuries Frozen Shoulder Rotator Cuff Tears Shoulder Dislocation Shoulder Impingement/Rotator Cuff Tendinitis Shoulder Injuries in the Throwing Athlete Shoulder Joint Tear (Glenoid Labrum Tear) Shoulder Separation SLAP Tears Treatments & Surgeries Shoulder Arthroscopy Shoulder Surgery Shoulder Joint Replacement Rotator Cuff Tears: Surgical Treatment Rotator Cuff and Shoulder Conditioning Reverse Total Shoulder Replacement Shoulder Physicians in Lubbock

" Arthritis, Sports Injuries, and more... "

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The neck provides the bridge between head and body. Similar to the back, it is made up of multiple muscles, tendons, ligaments, nerves, and bones. It houses the cervical spine and the vertebrae play a vital role in protecting the spine. This complex region places the importance of proper understanding of function to help properly strengthen in order to prevent injury. Though we don't normally see back or neck patients at Lubbock Sports Medicine, our team at Lubbock Sports Rehab is ready to provide effective and innovative therapy for you. At Lubbock Sports Rehab, the emphasis is placed on your body mechanics to treat the source of your pain. Since the site of your pain is not always the source of your pain, it takes a thorough, in-depth approach to fully treat you and your body. Come experience the difference at Lubbock Sports Rehab! Patient Education &Treatments Neck Pain Neck Sprain Backpack Guidelines Cervical Radiculopathy Cervical Spondylotic Myelopathy Neck Therapists in Lubbock Mark A. O'Keefe Mark Caffey Kerry Wimberly Jon Murray DPT, PT, MS, CAFS PT, CAFS LAT, ATC, FAFS LAT, ATC, FAFS

" Concussions, ImPACT Tests and more... "

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Protecting your head has become of increasing importance in sports today. With our expertise andcertified ImPACT clinicians, Lubbock Sports Medicine is the leading source for treatment of sports-related head injuries on the South Plains. Stan Kotara, PA, has been working with the ImPACT program with great success. Patient Education Concussion ImPACT Helmet Safety Return To Play Concussion Management Treatments Head Injury Treatment Concussion Treatment Helmet Information Getting back in the game ImPACT Assessments available at LSM ___________________________________________________________________________________________ What is the ImPACT program? ImPACT stands for Immediate Post-Concussion Assessment and Cognitive Testing. It is the premier concussion management program in the country and Lubbock Sports Medicine is bring it to you. This computerized evaluation system provides our clinicians with neurocognitive assessment tools and services that will be integral in return to play decisions. Have a look at the ImPACT Concussion Management Model for yourself and youll see why this is the leading concussion management program in the country! Important facts about the ImPACT Test: The ImPact Test is The ImPact Test is Not __________________________________________________________________________________________ Stan Kotara talks with Karen McKay on"Healthwise" about Concussion Management ___________________________________________________________________________________________________________ Head & Concussion Physicians in Lubbock

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Lubbock Sports Medicine & Rehab

Community Functions

Our director, Dr. Dandonas pioneering work in the diabetic center lead to his appointment as an advisor to Independent Health, Blue Cross, Blue Shield and to Community Blue in matters related to diabetes. Weve authored algorithms in diabetic management, which we disseminated to primary care physicians so that care of diabetes can be improved and its complications prevented.

Various community programs have been set up by the Center for the city, which include: Public health surveys which screens for hypercholesterolemia, diabetes, hypothyroidism and hypertension starting in 1995 and then annually thereafter. Data from initial surveys have shown us for the first time that 2/3 of Buffalos population has hypercholesterolemia (high cholesterol) and that the prevalence of diabetes in the region is eight percent. So far 9500 Western New Yorkers have been surveyed. Every year we do our best to raise funds for this activity which amounts to $45,000-50,000. These screenings are done in association with the Erie County Health Dept.

A unique Diabetes Patients Forum which meets every two months, since October 1996, which aims to empower and educate diabetic patients and their families. This forum aims to educate patients and their families regarding their conditions and empower them to ask questions regarding the management of their disease.

Endocrinology Diary for 2013

May: 2013

American College of Endocrinology and American Association of Clinical Endocrinologists, Phoenix, AZ This meeting was held in early May and one of the 10 chosen oral presentations was the one on the beneficial effects of testosterone in patients with hypogonadotropic hypogonadism. This led to a press release. Several abstracts based on clinical cases were presented by the fellows. These unique cases also raised a lot of interest.

Dr. Dandona participated in global consultants meeting related to the new anti-diabetic drug, TAK-875, from Takeda Pharmaceuticals in London, UK. This new class of drugs binds to a fatty acid receptor on the -cell in the pancreatic islet and induces the release of insulin. The fall in HbA1c is just under 1% and there is no risk of hypoglycemia. Dr Prabhakar Viswanathan, Senior Medical Director in Takeda, is leading the program to develop this drug. Dr Viswanathan is an ex-fellow from our research program from UB. He is the third fellow trained by Dr Dandona to hold such a senior position in a major pharmaceutical company. Drs Davinder (Dave) Gill and Jaswinder (Jaz) Gill (Sanofi-Aventis) are the other two.

June: 2013

Department of Medicine Research Day This day witnessed an outstanding performance by our division with the prizes for the best research and best case presentation being awarded to Manav Batra and Cherie Vaz.

Immunometabolism Symposium, Toronto Dr Dandona attended this meeting and contributed to the discussions during this meeting in relation to our groups large body of work linking metabolic states and macronutrient intake to oxidative stress and inflammation.

ADA meeting: Chicago IL

Abstracts on Research

Endocrine Society, San Francisco

Abstracts Presented with oral presentation

Our paper on effects of liraglutide in obese patients with type 1 diabetes is published online in Endocrine Practice. http://aace.metapress.com/content/76j38670g836wj7q/?p=3fd984e2fdd447458c5a69c2af65e691&pi=0

The new batch of Fellows joined. Dr Dandona was invited to be a member of the Special Programs Group of the Endocrine Society. Our paper linking obesity with asthma through an increased expression of asthma related genes in obesity was published in the journal, OBESITY.

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Diabetes Endocrinology Center of WNY

Overview

Aggressive treatment of malignant disease may produce unavoidable toxicities to normal cells. The mucosal lining of the gastrointestinal tract, including the oral mucosa, is a prime target for treatment-related toxicity by virtue of its rapid rate of cell turnover. The oral cavity is highly susceptible to direct and indirect toxic effects of cancer chemotherapy and ionizing radiation.[1] This risk results from multiple factors, including high rates of cellular turnover for the lining mucosa, a diverse and complex microflora, and trauma to oral tissues during normal oral function.[2] Although changes in soft tissue structures within the oral cavity presumably reflect the changes that occur throughout the gastrointestinal tract, this summary focuses on oral complications of antineoplastic drugs and radiation therapies.

It is essential that a multidisciplinary approach be used for oral management of the cancer patient before, during, and after cancer treatment. A multidisciplinary approach is warranted because the medical complexity of these patients affects dental treatment planning, prioritization, and timing of dental care. In addition, selected cancer patients (e.g., status posttreatment with high-dose head-and-neck radiation) are often at lifelong risk for serious complications such as osteoradionecrosis of the mandible. Thus, a multidisciplinary oncology team that includes oncologists, oncology nurses, and dental generalists and specialists as well as dental hygienists, social workers, dieticians, and related health professionals can often achieve highly effective preventive and therapeutic outcomes relative to oral complications in these patients.

While oral complications may mimic selected systemic disorders, unique oral toxicities emerge in the context of specific oral anatomic structures and their functions.

Frequencies of oral complications vary by cancer therapy; estimates are included in Table 1.

The most common oral complications related to cancer therapies are mucositis, infection, salivary gland dysfunction, taste dysfunction, and pain. These complications can lead to secondary complications such as dehydration, dysgeusia, and malnutrition. In myelosuppressed cancer patients, the oral cavity can also be a source of systemic infection. Radiation of the head and neck can irreversibly injure oral mucosa, vasculature, muscle, and bone, resulting in xerostomia, rampant dental caries, trismus, soft tissue necrosis, and osteonecrosis.

Severe oral toxicities can compromise delivery of optimal cancer therapy protocols. For example, dose reduction or treatment schedule modifications may be necessary to allow for resolution of oral lesions. In cases of severe oral morbidity, the patient may no longer be able to continue cancer therapy; treatment is then usually discontinued. These disruptions in dosing caused by oral complications can directly affect patient survivorship.

Management of oral complications of cancer therapy includes identification of high-risk populations, patient education, initiation of pretreatment interventions, and timely management of lesions. Assessment of oral status and stabilization of oral disease before cancer therapy are critical to overall patient care. Care should be both preventive and therapeutic to minimize risk for oral and associated systemic complications.

Future research targeted at developing technologies is needed to:

Development of new technologies to prevent cancer therapyinduced complications, especially oral mucositis, could substantially reduce the risk of oral pain, oral and systemic infections, and number of days in the hospital; and could improve quality of life and reduce health care costs. New technologies could also provide a setting in which novel classes of chemotherapeutic drugs, used at increased doses, could lead to enhanced cancer cure rates and durability of disease remission.

As has been noted, it is essential that a multidisciplinary approach be used for oral management of the cancer patient before, during, and after cancer treatment. This collaboration is pivotally important for the advancement of basic, clinical, and translational research associated with oral complications of current and emerging cancer therapies. The pathobiologic complexity of oral complications and the ever-expanding science base of clinical management require this comprehensive interdisciplinary approach.

In this summary, unless otherwise stated, evidence and practice issues as they relate to adults are discussed. The evidence and application to practice related to children may differ significantly from information related to adults. When specific information about the care of children is available, it is summarized under its own heading.

Oral complications associated with cancer chemotherapy and radiation result from complex interactions among multiple factors. The most prominent contributors are direct lethal and sublethal damage to oral tissues, attenuation of immune and other protective systems, and interference with normal healing. Principal causes can be attributed to both direct stomatotoxicity and indirect stomatotoxicity. Direct toxicities are initiated via primary injury to oral tissues. Indirect toxicities are caused by nonoral toxicities that secondarily affect the oral cavity, including the following:

Understanding of mechanisms associated with oral complications continues to increase. Unfortunately, there are no universally effective agents or protocols to prevent toxicity. Elimination of preexisting dental/periapical, periodontal, and mucosal infections; institution of comprehensive oral hygiene protocols during therapy; and reduction of other factors that may compromise oral mucosal integrity (e.g., physical trauma to oral tissues) can reduce frequency and severity of oral complications in cancer patients (refer to the Oral and Dental Management Before Cancer Therapy and the Oral and Dental Management After Cancer Therapy sections of this summary for further information).[1]

Complications can be acute (developing during therapy) or chronic (developing months to years after therapy). In general, cancer chemotherapy causes acute toxicities that resolve following discontinuation of therapy and recovery of damaged tissues. In contrast, radiation protocols typically cause not only acute oral toxicities, but induce permanent tissue damage that result in lifelong risk for the patient.

Risk factors for oral complications (see Table 2) derive from both direct damage to oral tissues secondary to chemotherapy and indirect damage due to regional or systemic toxicity. For example, therapy-related toxicity to oral mucosa can be exacerbated by colonizing oral microflora when local and systemic immune function is concurrently compromised. Frequency and severity of oral complications are directly related to extent and type of systemic compromise.

Ulcerative oral mucositis occurs in approximately 40% of patients receiving chemotherapy. In approximately 50% of these patients, the lesions are severe and require medical intervention including modification of their cytotoxic cancer therapy. Normal oral mucosal epithelium is estimated to undergo complete replacement every 9 to 16 days. Intensive chemotherapy can cause ulcerative mucositis that initially emerges approximately 2 weeks after initiation of high-dose chemotherapy.[2-4]

Chemotherapy directly impairs replication of basal epithelial cells; other factors, including proinflammatory cytokines and metabolic products of bacteria, may also play a role. The labial mucosa, buccal mucosa, tongue, floor of mouth, and soft palate are more severely affected by chemotherapy than are the attached, heavily keratinized tissues such as the hard palate and gingiva; this may be caused by relative rate of epithelial cell turnover among high-risk versus low-risk oral mucosal tissues. Topical cryotherapy may ameliorate mucositis caused by agents such as 5-fluorouracil (5-FU) by reducing vascular delivery of these toxic agents to replicating oral epithelium.[5]

It is difficult to predict whether a patient will develop mucositis strictly on the basis of the classes of drugs that are administered. Several drugs are associated with a propensity to damage oral mucosa:

Anecdotal evidence suggests that patients who experience mucositis with a specific chemotherapy regimen during the first cycle will typically develop comparable mucositis during subsequent courses of that regimen.

Other oral complications typically include infections of the mucosa, dentition/periapices, and periodontium. Prevalence of these infections has been substantiated in multiple studies.[8-11] Specific criteria for determining risk of infectious flare during myelosuppression have not been developed. Guidelines for assessment primarily address both degree of severity of the chronic lesion and whether acute symptoms have recently (i.e., <90 days) developed. However, chronic asymptomatic periodontitis may also represent a focus for systemic infectious complications since bacteria, bacterial cell wall substances, and inflammatory cytokines may translocate into the circulation via ulcerated pocket epithelium.[10] In addition, poor oral hygiene and periodontitis seem to increase the prevalence of pulmonary infections in high-risk patients.[12]

Resolution of oral toxicity, including mucositis and infection, generally coincides with granulocyte recovery. This relationship may be temporally but not causally related. For example, oral mucosal healing in hematopoietic stem cell transplantation patients is only partially dependent on rate of engraftment, especially neutrophils.

Head and neck radiation can cause a wide spectrum of oral complications (refer to the list of Oral Complications of Radiation Therapy). Ulcerative oral mucositis is a virtually universal toxicity resulting from this treatment; there are clinically significant similarities as well as differences compared with oral mucositis caused by chemotherapy.[2] In addition, oral mucosal toxicity can be increased by use of head and neck radiation together with concurrent chemotherapy.

Head and neck radiation can also induce damage that results in permanent dysfunction of vasculature, connective tissue, salivary glands, muscle, and bone. Loss of bone vitality occurs:

These changes can lead to soft tissue necrosis and osteonecrosis that result in bone exposure, secondary infection, and severe pain.[11]

Oral Complications of Radiation Therapy

Unlike chemotherapy, however, radiation damage is anatomically site-specific; toxicity is localized to irradiated tissue volumes. Degree of damage depends on treatment regimen-related factors, including type of radiation utilized, total dose administered, and field size/fractionation. Radiation-induced damage also differs from chemotherapy-induced changes in that irradiated tissue tends to manifest permanent damage that places the patient at continual risk for oral sequelae. The oral tissues are thus more easily damaged by subsequent toxic drug or radiation exposure, and normal physiologic repair mechanisms are compromised as a result of permanent cellular damage.

Poor oral health has been associated with increased incidence and severity of oral complications in cancer patients, hence the adoption of an aggressive approach to stabilizing oral care before treatment.[1,2] Primary preventive measures such as appropriate nutritional intake, effective oral hygiene practices, and early detection of oral lesions are important pretreatment interventions.

There is no universally accepted precancer therapy dental protocol because of the lack of clinical trials evaluating the efficacy of a specific protocol. A systematic review of the literature revealed two articles on oral care protocols prior to cancer therapy.[3] One study examined the benefits of a minimal intervention precancer therapy (mostly chemotherapy) dental protocol, and the other examined the impact of an intensive preventive protocol on patients undergoing chemotherapy. Both studies had several flaws, including small sample size or the lack of comparison groups.[3]

The involvement of a dental team experienced with oral oncology may reduce the risk of oral complications via either direct examination of the patient or in consultation with the community-based dentist. The evaluation should occur as early as possible before treatment.[4,5] The examination allows the dentist to determine the status of the oral cavity before cancer treatment begins and to initiate necessary interventions that may reduce oral complications during and after that therapy. Ideally, this examination should be performed at least 1 month before the start of cancer treatment to permit adequate healing from any required invasive oral procedures. A program of oral hygiene should be initiated, with emphasis on maximizing patient compliance on a continuing basis.

Oral evaluation and management of patients scheduled to undergo myeloablative chemotherapy should occur as early as possible before initiation of therapy (refer to the list on Oral Disease Stabilization Before Chemotherapy and/or Hematopoietic Stem Cell Transplantation). To maximize outcomes, the oncology team should clearly advise the dentist as to the patients medical status and oncology treatment plan. In turn, the dental team should delineate and communicate a plan of care for oral disease management before, during, and after cancer therapy.[5]

Oral Disease Stabilization Before Chemotherapy and/or Hematopoietic Stem Cell Transplantation

The overall goal is to complete a comprehensive oral care plan that eliminates or stabilizes oral disease that could otherwise produce complications during or following chemotherapy. Achieving this goal will most likely reduce risk of oral toxicities with resultant reduced risk for systemic sequelae, reduced cost of patient care, and enhanced quality of life. If the patient is unable to receive the medically necessary oral care in the community, the oncology team should assume responsibility for oral management.

It is important to realize that dental treatment plans need to be realistic relative to type and extent of dental disease and how long it could be before resumption of routine dental care. For example, teeth with minor caries may not need restoration before cancer treatment begins, especially if more conservative disease stabilization strategies can be used (e.g., aggressive topical fluoride protocols, temporary restorations, or dental sealants).

Specific interventions are directed to:

Guidelines for dental extractions, endodontic management, and related interventions (see Table 3) can be used as appropriate.[6,7] Antibiotic prophylaxis prior to invasive oral procedures may be warranted in the context of central venous catheters; the current American Heart Association (AHA) protocol for infective endocarditis and oral procedures is frequently used for these patients.

Stages of assessment have been described relative to the hematopoietic stem cell transplant patient (see Table 4).[5] This model provides a useful classification for neutropenic cancer patients in general. Type, timing, and severity of oral complications represent the interaction of local and systemic factors that culminate in clinical expression of disease. Correlating oral status with systemic condition of the patient is thus critically important.

Selected conditioning regimens characterized by reduced intensity for myelosuppression have been used in patients. These regimens have generally been noted to significantly reduce the severity of oral complications early posttransplant, especially for mucositis and infection risk. The guidelines listed in Table 4 can be adjusted to reflect these varying degrees of risk, based on the specific conditioning regimen to be used.

Phase I: Before Chemotherapy

Oral complications are related to current systemic and oral health, oral manifestations of underlying disease, and oral complications of recent cancer or other medical therapy. During this period, oral trauma and clinically significant infections, including dental caries, periodontal disease, and pulpal infection, should be eliminated. Additionally, patients should be educated relative to the range and management of oral complications that may occur during subsequent phases. Baseline oral hygiene instructions should be provided. It is especially important to note whether patients have been treated with bisphosphonates (e.g., patients with multiple myeloma) and to plan their care accordingly.

Phase II: Neutropenic Phase

Oral complications arise primarily from direct and indirect stomatotoxicities associated with high-dose chemotherapy or chemoradiotherapy and their sequelae. Mucositis, xerostomia, and those lesions related to myelosuppression, thrombocytopenia, and anemia predominate. This phase is typically the period of high prevalence and severity of oral complications.

Oral mucositis usually begins 7 to 10 days after initiation of cytotoxic therapy and remains present for approximately 2 weeks after cessation of that therapy. Viral, fungal, and bacterial infections may arise, with incidence dependent on the use of prophylactic regimens, oral status prior to chemotherapy, and duration/severity of neutropenia. Frequency of infection declines upon resolution of mucositis and regeneration of neutrophils. This phenomenon appears to be more a temporal relation than a causative one, based on the predominant evidence. Despite the initial marrow recovery, however, the patient may remain at risk for infection, depending on status of overall immune reconstitution.

Salivary gland hypofunction/xerostomia secondary to anticholinergic drugs and taste dysfunction is initially detected in this phase; the toxicity typically resolves within 2 to 3 months.

In allogeneic transplant patients, while uncommon, hyperacute graft-versus-host disease (GVHD) can occur and can result in significant oral mucosal inflammation and breakdown that can complicate the oral course for patients. Clinical presentation will often not be sufficiently distinct to diagnosis this lesion. The clinical assessment is typically based on the patient experiencing more-severe-than-expected mucositis that will often not heal within the time line for mucosal recovery associated with oral mucositis caused by chemotherapy.

Phase III: Hematopoietic Recovery

Frequency and severity of acute oral complications typically begin to decrease approximately 3 to 4 weeks after cessation of chemotherapy. Healing of ulcerative oral mucositis in the setting of marrow regeneration contributes to this dynamic. Although immune reconstitution is developing, oral mucosal immune defenses may not be optimal. Generally stated, immune reconstitution will take between 6 and 9 months for autologous transplant patients and between 9 and 12 months for allogeneic transplant patients not developing chronic GVHD. Thus, the patient remains at risk for selected infection, including candidal and herpes simplex virus infections.

Mucosal bacterial infections during this phase occur less frequently unless engraftment is delayed or the patient has acute GVHD or is receiving GVHD therapy. Most centers will use systemic infection prophylaxis throughout this period (and, in many instances, longer) to reduce the risk of infections in general, a practice that positively influences the rate and severity of both systemic and local oral infections.

The hematopoietic stem cell transplant patient represents a unique cohort at this point. For example, risk for acute oral GVHD typically emerges during this time in allogeneic graft recipients.

Phase IV: Immune Reconstitution/Recovery from Systemic Toxicity

Oral lesions are principally related to chronic conditioning regimenassociated (chemotherapy with or without radiation therapy) toxicity and, in the allogeneic patient, GVHD. Late viral infections and xerostomia predominate. Mucosal bacterial infections are infrequent unless the patient remains neutropenic or has severe chronic GVHD.

Risk exists for graft failure, cancer relapse, and second malignancies. The hematopoietic stem cell transplant patient may develop oral manifestations of chronic GVHD during this period.

Phase V: Long-term Survival

Long-term survivors of cancer treated with high-dose chemotherapy alone or chemoradiotherapy will generally have few significant permanent oral complications.

Risk for radiation-induced chronic complications is related to the total dose and schedule of radiation therapy. Regimens that incorporate total body irradiation may result in permanent salivary gland hypofunction/xerostomia,[8] which is the most frequently reported late oral complication. Permanent salivary gland dysfunction can occur in autologous transplant patients in addition to nonautologous recipients. Other significant complications include craniofacial growth and developmental abnormalities in pediatric patients, and emergence of second malignancies of the head/neck region.

Routine systematic oral hygiene is important for reducing incidence and severity of oral sequelae of cancer therapy. The patient must be informed of the rationale for the oral hygiene program as well as the potential side effects of cancer chemotherapy and radiation therapy. Effective oral hygiene is important throughout cancer treatment, with emphasis on oral hygiene beginning before treatment starts.[1]

Management of patients undergoing either high-dose chemotherapy or upper-mantle radiation share selected common principles. These principles are based on baseline oral care (refer to the list of suggestions for Routine Oral Hygiene Care) and reduction of physical trauma to oral mucosa (refer to the list of Guidelines for Management of Dentures and Orthodontic Appliances in Patients Receiving High-Dose Cancer Therapy).

Routine Oral Hygiene Care

Guidelines for Management of Dentures and Orthodontic Appliances in Patients Receiving High-Dose Cancer Therapy [1]

Considerable variation exists across institutions relative to specific nonmedicated approaches to baseline oral care, given limited published evidence. Most nonmedicated oral care protocols use topical, frequent (every 46 hours) rinsing with 0.9% saline. Additional interventions include dental brushing with toothpaste, dental flossing, ice chips, and sodium bicarbonate rinses. Patient compliance with these agents can be maximized by comprehensive overseeing by the health care professional.

Patients using removable dental prostheses or orthodontic appliances have risk of mucosal injury or infection. This risk can be eliminated or substantially reduced prior to high-dose cancer therapy. (Refer to the list of Guidelines for Management of Dentures and Orthodontic Appliances in Patients Receiving High-Dose Cancer Therapy.)

Dental brushing and flossing represent simple, cost-effective approaches to bacterial dental plaque control. This strategy is designed to reduce risk of oral soft tissue infection during myeloablation. Oncology teams at some centers promote their use, while teams at other centers have patients discontinue brushing and flossing when peripheral blood components decrease below defined thresholds (e.g., platelets <30,000/mm3). There is no comprehensive evidence base regarding the optimal approach. Many centers adopt the strategy that the benefits of properly performed dental brushing and flossing in reducing risk of gingival infection outweigh the risks.

Periodontal infection (gingivitis and periodontitis) increases risk for oral bleeding; healthy tissues should not bleed. Discontinuing dental brushing and flossing can increase risk for gingival bleeding, oral infection, and bacteremia. Risk for gingival bleeding and infection, therefore, is reduced by eliminating gingival infection before therapy and promoting oral health daily by removing bacterial plaque with gentle debridement with a soft or ultra-soft toothbrush during therapy. Mechanical plaque control not only promotes gingival health, but it also may decrease risk of exacerbation of oral mucositis secondary to microbial colonization of damaged mucosal surfaces.

Dental brushing and flossing should be performed daily under the supervision of professional staff:

Patients skilled at flossing without traumatizing gingival tissues may continue flossing throughout chemotherapy administration. Flossing allows for interproximal removal of dental bacterial plaque and thus promotes gingival health. As with dental brushing, this intervention should be performed under the supervision of professional staff to ensure its safe administration.

The oral cavity should be cleaned after meals:

Preventing dryness of the lips to reduce risk for tissue injury is important. Mouth breathing and/or xerostomia secondary to anticholinergic medications used for nausea management can induce the condition. GVHD of the lips can also contribute to dry lips in allogeneic transplant patients. Lip care products containing petroleum-based oils and waxes can be useful. Lanolin-based creams and ointments may be more effective in moisturizing/lubricating the lips and thus protecting against trauma.

The terms oral mucositis and stomatitis are often used interchangeably at the clinical level, but they do not reflect identical processes.

Oral Mucositis:

Stomatitis:

Risk of oral mucositis has historically been characterized by treatment-based and patient-based variables.[4] The current model of oral mucositis involves a complex trajectory of molecular, cellular, and tissue-based changes. There is increasing evidence of genetic governance of this injury,[5-8] characterized in part by upregulation of nuclear factor kappa beta and inflammatory cytokines (e.g., tumor necrosis factor-alpha) and interleukin-1 in addition to epithelial basal cell injury. Comprehensive knowledge of the molecular-based causation of the lesion has contributed to targeted drug development for clinical use.[9] The pipeline of new drugs in development (e.g., recombinant human intestinal trefoil factor [10] may lead to strategic new advances in the ability of clinicians to customize the prevention and treatment of oral mucositis in the future.[11]

Erythematous mucositis typically appears 7 to 10 days after initiation of high-dose cancer therapy. Clinicians should be alert to the potential for increased toxicity with escalating dose or treatment duration in clinical trials that demonstrate gastrointestinal mucosal toxicity. High-dose chemotherapy, such as that used in the treatment of leukemia and hematopoietic stem cell transplant regimens, may produce severe mucositis. Mucositis is self-limited when uncomplicated by infection and typically heals within 2 to 4 weeks after cessation of cytotoxic chemotherapy.

Systematic assessment of the oral cavity following treatment permits early identification of lesions.[12-16] Oral hygiene and other supportive care measures are important to minimizing the severity of the lesion.

In an effort to standardize measurements of mucosal integrity, oral assessment scales have been developed to grade the level of stomatitis by characterizing alterations in lips, tongue, mucous membranes, gingiva, teeth, pharynx, quality of saliva, and voice.[12-14] Specific instruments of assessment have been developed to evaluate the observable and functional dimensions of mucositis. These evaluative tools vary in complexity.

Prophylactic measures and treatment options should be employed by practitioners for patients in the appropriate clinical settings. Specific recommendations for minimizing oral mucositis include the following:

Updated guidelines from the American Society of Clinical Oncology for the prevention and treatment of mucositis were published in 2007 [17] and include the following:

Specific recommendations against specific practices include the following:

Oral mucositis in hematopoietic stem cell transplantation patients produces clinically significant toxicities that require multiprofessional interventions.[18-25] The lesion can increase risk of systemic infection,[1] produce clinically significant pain,[26][Level of evidence: II] and promote oral hemorrhage. It can also compromise the upper airway such that endotracheal intubation is required. Use of total parenteral nutrition is often necessary because of the patients inability to receive enteral nutrition.

Once mucositis has developed, its severity and the patients hematologic status govern appropriate oral management. Meticulous oral hygiene and palliation of symptoms are essential. Some established guidelines for oral care include oral assessments twice daily for hospitalized patients and frequent oral care (minimum of every 4 hours and at bedtime) that increases in frequency as the severity of mucositis increases.

Oral care protocols generally include atraumatically cleansing the oral mucosa, maintaining lubrication of the lips and oral tissues, and relieving pain and inflammation. Several health professional organizations have produced evidence-based oral mucositis guidelines. These organizations include but are not limited to the following:

In many cases, there is similarity in recommendations across the organizations. The Cochrane Collaboration, however, uses a meta-analysis approach and thus provides a unique context for purposes of guideline construction.

Palifermin (Kepivance), also known as keratinocyte growth factor-1, has been approved to decrease the incidence and duration of severe oral mucositis in patients with hematologic cancers undergoing conditioning with high-dose chemotherapy, with or without radiation therapy, followed by hematopoietic stem cell rescue.[9][Level of evidence: I] The standard dosing regimen is three daily doses before conditioning and three additional daily doses starting on day 0 (day of transplant). Palifermin has also been shown in a randomized, placebo-controlled trial to reduce the incidence of oral mucositis in patients with metastatic colorectal cancer treated with fluorouracil-based chemotherapy.[30][Level of evidence: I] In addition, a single dose of palifermin prevented severe oral mucositis in patients who had sarcoma and were receiving doxorubicin-based chemotherapy.[31][Level of evidence: I]

In two randomized, placebo-controlled trials conducted in head/neck cancer patients undergoing postoperative chemoradiotherapy and in patients receiving definitive chemoradiotherapy for locally advanced head/neck cancer, intravenous palifermin administered weekly for 8 weeks decreased severe oral mucositis,[32,33][Level of evidence: I] as graded by providers using standard toxicity assessments and during multicycle chemotherapy.[31] Patient-reported outcomes related to mouth and throat soreness and to treatment breaks or compliance were not significantly different between arms in either trial. In one study, opioid analgesic use was also not significantly different between arms.[33]

Evidence from several studies has supported the potential efficacy of low-level laser therapy in addition to oral care to decrease the duration of chemotherapy-induced oral mucositis in children.[34][Level of evidence: I][35][Level of evidence: I]

Mucositis Management

Management of oral mucositis via topical approaches should address efficacy, patient acceptance, and appropriate dosing. A stepped approach is typically used, with progression from one level to the next as follows:

Normal saline solution is prepared by adding approximately 1 tsp of table salt to 32 oz of water. The solution can be administered at room or refrigerated temperatures, depending on patient preference. The patient should rinse and swish approximately 1 tbsp, followed by expectoration; this can be repeated as often as necessary to maintain oral comfort. Sodium bicarbonate (12 tbsp/qt) can be added, if viscous saliva is present. Saline solution can enhance oral lubrication directly as well as by stimulating salivary glands to increase salivary flow.

A soft toothbrush that is replaced regularly should be used to maintain oral hygiene.[17] Foam-swab brushes do not effectively clean teeth and should not be considered a routine substitute for a soft nylon-bristled toothbrush; additionally, the rough sponge surface may irritate and damage the mucosal surfaces opposite the tooth surfaces being brushed.

On the basis of nonoral mucosa wound-healing studies, the repeated use of hydrogen peroxide rinses for daily preventive oral hygiene is not recommended, especially if mucositis is present, because of the potential for damage to fibroblasts and keratinocytes, which can cause delayed wound healing.[36-39] Using 3% hydrogen peroxide diluted 1:1 with water or normal saline to remove hemorrhagic debris may be helpful; however, this approach should only be used for 1 or 2 days because more extended use may impair timely healing of mucosal lesions associated with bleeding.[40]

Focal topical application of anesthetic agents is preferred over widespread oral topical administration, unless the patient requires more extensive pain relief. Products such as the following may provide relief:

The use of compounded topical anesthetic rinses should be considered carefully relative to the cost of compounding these products versus their actual efficacy.

Irrigation should be performed before topical medication is applied because removal of debris and saliva allows for better coating of oral tissues and prevents material from accumulating. Frequent rinsing cleans and lubricates tissues, prevents crusting, and palliates painful gingiva and mucosa.

Systemic analgesics should be administered when topical anesthetic strategies are not sufficient for clinical relief. Opiates are typically used;[26][Level of evidence: II] the combination of chronic indwelling venous catheters and computerized drug administration pumps to provide PCA has significantly increased the effectiveness of controlling severe mucositis pain while lowering the dose and side effects of narcotic analgesics. Nonsteroidal anti-inflammatory drugs that affect platelet adhesion and damage gastric mucosa are contraindicated, especially if thrombocytopenia is present.

Although mucositis continues to be one of the dose-limiting toxicities of fluorouracil (5-FU), cryotherapy may be an option for preventing oral mucositis. Because 5-FU has a short half-life (520 minutes), patients are instructed to swish ice chips in their mouths for 30 minutes, beginning 5 minutes before 5-FU is administered.[41][Level of evidence: I] Oral cryotherapy has been studied in patients receiving high-dose melphalan conditioning regimens used with transplantation;[42,43] further research is needed.

Many agents and protocols have been promoted for management or prevention of mucositis.[44-46] Although not adequately supported by controlled clinical trials, allopurinol mouthwash and vitamin E have been cited as agents that decrease the severity of mucositis. Prostaglandin E2 was not effective as a prophylaxis of oral mucositis following bone marrow transplant, although studies indicate possible efficacy when prostaglandin E2 is administered via a different dosing protocol.

Check the list of NCI-supported cancer clinical trials for supportive and palliative care trials about mucositis that are now accepting participants. The list of trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI website.

Pain in cancer patients may arise from onset of the disease through survivorship and may be:[1]

Cancer pain causes increased morbidity, reduced performance status, increased anxiety and depression, and diminished quality of life (QOL). Dimensions of acute and chronic pain include the following:

Management of head and neck pain and oral pain may be particularly challenging because eating, speech, swallowing, and other motor functions of the head and neck and oropharynx are constant pain triggers.

Continue reading here:
Oral Complications of Chemotherapy and Head/Neck Radiation ...

Personalized medicine is the use of detailed information about a patient's genotype or level of gene expression and a patient's clinical data in order to select a medication, therapy or preventative measure that is particularly suited to that patient at the time of administration. The benefits of this approach are in its accuracy, efficacy, safety and speed. The term emerged in the late 1990s with progress in the Human Genome Project. Research findings over the past decade, or so, in biomedical research have unfolded a series of new, predictive sciences that share the appendage -omics (genomics, proteomics, metabolomics, cytomics). These are opening the possibility of a new approach to drug development as well as unleashing the potential of significantly more effective diagnosis, therapeutics, and patient care.

Traditional diagnosis focuses on the symptoms of a patient's illness whereas a personalized medicine approach can directly examine and analyse the genetic basis of a disease and stratify the total population into different sub-sets each with common, but unique, disease characteristics.

The pharmaceutical industry has worked on the basis of offering a therapy that is intended to suit the population at large based on what is known as the 'blockbuster drug model'. A blockbuster drug is a product capable of achieving sales of over $1 billion per annum. The pharmaceutical industry is facing severe difficulties across several spectrums with its blockbuster approach:

There are several stakeholders: the industry, the regulators, the payors, the patients and the general public

The pharmaceutical industry, in general, has been reluctant to the immediately embrace the potential of personalized medicine. It is believed that they are concerned that the emergence of personalized medicine will destroy the foundations of the mass-market blockbuster drug model because personalized therapeutics will cater for particular sub-sets of the general population.

Another reason for the scepticism of the pharmaceutical industry is the threat to existing products. Many blockbuster drugs, such as Lipitor, compare favorably with cheaper generic drugs only in a small percentage of patients. But since it is not known how to identify these, many physicians prescribe the expensive drug to all their patients. If a test could be devised to determine who actually benefits from the more expensive drug, all other patients could use the generic.

However, the technologies underpinning personalized medicine could enable the pharmaceutical industry to become more sure-footed. A more efficient drug development process, based on sound, robust genetic evidence could require less investment and, perhaps less elapsed time, to identify and develop new products as confidence deepens. Furthermore, the idea of a therapeutic being marketed on the basis of a companion theranostic test result could deepen and prolong consumer loyalty if sustainable benefits are evident.

The traditional diagnostics industry is mature and only achieving a growth rate of the order of 4% per annum. Its products are very cost sensitive and have a relatively short life cycle. The diagnostics industry has not been as successful as the pharmaceutical industry in attracting investment funding.

However, the advent of molecular diagnostic tests, or theranostics, opens new opportunities in a small but believed to be rapidly growing niche market. New relationships are likely to develop between industry partners committed to personalized medicine embracing the approach of successful, specialised pharmaceutical firms. Such has been the case with IBM. This corporation has made strategic partnerships with Mayo Clinic Medical Center and several other healthcare and testing centres. Its plan entails developing bioinformatics systems which will allow greater growth in tests that are available.

Still the major problem in growth of tests such as these is their clinical utility as well as reimbursement from third party payors.

The emergence of personalized medicine raises issues for those who pay for treatment. The unit cost is likely to he higher but it is argued that the total cost of a treatment cycle will be lower overall. Furthermore, the possibilities of the predicitive potential of personalized medicine ought to avert costly intensive care treatment when a disease is established.

The response of payers will be influenced by the nature of the relationship they have with those whom they are paying for. Is it a long-term relationship, which is the case with nationally funded medical care, or is it short term? New policies and procedures will be necessary.

Countries such as the United States are currently struggling with the burgeoning of healthcare expenditure. Perhaps personalized medicine is the cure. However, most US private insurers unlike the governmental system are not embracing this potential. Less than 5% of all private companies reimburse for genetic tests.

The Food and Drug Administration in the United States and their counterparts appear convinced that personalized medicine is going to make a profound impact on society and they are guiding this process.

Dr Andrew VonEschenbach, Director of the FDA recently gave a briefing to the Personalized Medicine Coalition at the National Press Club. He and the organization are truly committed to bring new testing and treatment to market which is molcularly based. His feeling is that the Molecular Metamorphosis is equivalent if not greater than the bacterial theory and its revolution of medicine.

Personalized medicine has the potential to revolutionize the practice of medicine, but despite significant scientific advances, very few genomics-based tests or treatments have reached consumers. Senator Barack Obama introduced the Genomics and Personalized Medicine Act to overcome the scientific barriers, adverse market pressures, and regulatory obstacles that have stood in the way of better medicine.[1] In addition, in the United States. The Secretary of Health and Human Services Mike Leavitt has made personalized medicine the top priority during his tenure. He has created a committee that is called the Secretary's Advisory Committee on Genetics Health and Society aka. SACGHS During the March meeting there was briefing re-affirming his commitment to this wonderful new phase of medical care.

One of the significant barriers to genetic testing is thought to be the fear of discrimination. Discirimination from an insurer or even worse and employer. This fear has been indicated in several polls, including the Harris Poll in 2002. For the last decade there has been some form of legislation which had been mired in the House of Representatives in the United States. The current bill is called the Genetic Information Nondiscrimination Act H.R. 493, S.358 aka GINA. It was passed in the House of Representatives 420-3 and appears to have major support in the Senate. This will legislation will break down a significant barrier to this technology

Patients will clearly be influenced by proven success as is the case with Herceptin and Gleevec. Theranostic tests are proving effective in other areas such as the identification of anti-retroviral drug for use with different strains of HIV.

At a recent meeting of the US Secretary's Advisory Committee on Genetics Health and Society it was revealed that a majority of the public supports the utilization of genetic testing, especially if this testing could be used to improve health outcomes.

Public education public confidence about the potential benefits of personalized medicine will be an important facet of its widespread acceptance. This includes about the research itself and the science underlying it; disease variations and the approach to prevention, treatment and care; and a deeper awareness of risks and benefits attaching to clinical trials.

The march toward personalized medicine is not driven, in some instances, on the basis of scientific hypothesis but through hypothesis generation sometimes starting with natural history. The key task is to find genes and gene variations that play a role in a disease. The first step is to associate the occurrence of a particualr gene variant with the incidence of a particular disease or disease predisposition - an association that can vary from one individual to another depending on many factors, including environmental circumstances. The outcome is the development of biomarkers which are stable and predictive. Today's biomarker is tomorrow's theranostic.

The infrastructure necessary includes molecular information -biological specimens derived from tissue, cells, or blood provided on the basis of informed donor consent and suitably annotated. Clinical information is also necessary based on patient medical records or clinical trial data.

A very high level of collaboration involving scientists and specialists from varying disciplines is required to integrate and make sense of all this information.

The Harvard Partners Center for Genetics and Genomics was founded in 2001 with the specific goal of accelerating the realization of personalized medicine. The Personal Genome Project was announced by George Church in 2006; it will publish full genome sequences and medical records of volunteers in order to enable research into personalized medicine.

Not only is personalized medicine tailoring the right drug, for the right person, at the right time but it also includes evaluating predisposition to disease sometimes decades in advance of its threatened onset.

Cancer genetics is a subspecialized field of genetics. This field initially dealt with the relatively small amount of inherited cancers. This amounted to about 5-10% of all cancers as estimated bt the National Institutes of Health.

Individuals diagnosed with familial breast, ovarian, colon cancer had been counseled in the past that they would receive standardized treatments and had limited options before their "condition" arrived. These options included removal of the organs that may give rise to cancer. Recent medical research indicates that medications, lifestyle changes and increased screening can mitigate some risk. An example is BRCA mutations where the carrier can have an increased lifetime risk of 85% for developing a breast cancer or up to 40% increased risk of getting ovarian cancer. Now medications such as tamoxifen are being shown to reduce incidence of disease.

The exciting news is that cancer predisposition genes and families are being identified by genetic testing and research at a break neck pace. Because all cancers require a dysfunction in the DNA of cells that regulate growth, it would be foolhardy not to expect all cancers to have some heritable predisposition as well as environmental influence.

Personalized medicine aims to identify these families at risk for cancer, heart disease, diabetes, etc. Once identified by simple family history including a 3 generation pedigree or advanced genetic testing, the person could take preventative action. This might include changes in diet, cessation of toxic habits, earlier screening, exercise, prophylactic medications or surgery.

Two products, Herceptin supplied by Genentech and Gleevec supplied by Novartis,are prescribed on the basis of the outcome of a companion theranostic test. Herceptin treats a category of breast cancer in woman and the test helps identify those patients whose cancer cells express the protein HER2 making them eligible. Herceptin sales have grown from $30.5 million in 1998, its year of introduction, to $764 million in 2005. Gleevec treats chronic myeloid leukaemia (CML) arrived in 2004 and it is known as a targeted cancer drug. In addition because of new molecular testing for c-kit, tumors such as GIST GastroIntestinal Stromal Tumours a solid malignancy never associated with blood bourne cancer are also treated with this drug. It works by killing specific cells whereas chemotherapy can kill both deranged and healthy cells. Because of this ability to molecularly detect true disease causing mutation a whole new reclassification of cancer has begun. So has the unimagined use of several of these "targeted" drugs. Gleevec sales have exceeded $500 million.

There are several universities involved in translating the burgeoning science into use. The difficulty is that medical education in all countries does not provide adequate genetic instruction.

A small number of universities are currently developing a subspecialty in medicine that is known by several names including, molecular medicine, personalized medicine, or even prospective medicine. These include, Duke University in North Carolina USA, Harvard in Cambridge USA, The Mount Sinai Hospital in New York City. A medical school is currently being constructed in Arizona USA to teach the field of personalized medicine; this is a project of Arizona State University and a company called TGen.

Aside from academic universities, private programs such as Helix Health LLP in New York City provide genetics consultation to accomplish personalized medical care. Their mission is to educate and empower patients and physicians in this new paradigm of medicine.

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Persons using assistive technology might not be able to fully access information in this file. For assistance, please send e-mail to: mmwrq@cdc.gov. Type 508 Accommodation and the title of the report in the subject line of e-mail.

Please note: An erratum has been published for this article. To view the erratum, please click here.

Clare A. Dykewicz, M.D., M.P.H. Harold W. Jaffe, M.D., Director Division of AIDS, STD, and TB Laboratory Research National Center for Infectious Diseases

Jonathan E. Kaplan, M.D. Division of AIDS, STD, and TB Laboratory Research National Center for Infectious Diseases Division of HIV/AIDS Prevention --- Surveillance and Epidemiology National Center for HIV, STD, and TB Prevention

Clare A. Dykewicz, M.D., M.P.H., Chair Harold W. Jaffe, M.D. Thomas J. Spira, M.D. Division of AIDS, STD, and TB Laboratory Research

William R. Jarvis, M.D. Hospital Infections Program National Center for Infectious Diseases, CDC

Jonathan E. Kaplan, M.D. Division of AIDS, STD, and TB Laboratory Research National Center for Infectious Diseases Division of HIV/AIDS Prevention --- Surveillance and Epidemiology National Center for HIV, STD, and TB Prevention, CDC

Brian R. Edlin, M.D. Division of HIV/AIDS Prevention---Surveillance and Epidemiology National Center for HIV, STD, and TB Prevention, CDC

Robert T. Chen, M.D., M.A. Beth Hibbs, R.N., M.P.H. Epidemiology and Surveillance Division National Immunization Program, CDC

Raleigh A. Bowden, M.D. Keith Sullivan, M.D. Fred Hutchinson Cancer Research Center Seattle, Washington

David Emanuel, M.B.Ch.B. Indiana University Indianapolis, Indiana

David L. Longworth, M.D. Cleveland Clinic Foundation Cleveland, Ohio

Philip A. Rowlings, M.B.B.S., M.S. International Bone Marrow Transplant Registry/Autologous Blood and Marrow Transplant Registry Milwaukee, Wisconsin

Robert H. Rubin, M.D. Massachusetts General Hospital Boston, Massachusetts and Massachusetts Institute of Technology Cambridge, Massachusetts

Kent A. Sepkowitz, M.D. Memorial-Sloan Kettering Cancer Center New York, New York

John R. Wingard, M.D. University of Florida Gainesville, Florida

John F. Modlin, M.D. Dartmouth Medical School Hanover, New Hampshire

Donna M. Ambrosino, M.D. Dana-Farber Cancer Institute Boston, Massachusetts

Norman W. Baylor, Ph.D. Food and Drug Administration Rockville, Maryland

Albert D. Donnenberg, Ph.D. University of Pittsburgh Pittsburgh, Pennsylvania

Pierce Gardner, M.D. State University of New York at Stony Brook Stony Brook, New York

Roger H. Giller, M.D. University of Colorado Denver, Colorado

Neal A. Halsey, M.D. Johns Hopkins University Baltimore, Maryland

Chinh T. Le, M.D. Kaiser-Permanente Medical Center Santa Rosa, California

Deborah C. Molrine, M.D. Dana-Farber Cancer Institute Boston, Massachusetts

Keith M. Sullivan, M.D. Fred Hutchinson Cancer Research Center Seattle, Washington

CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation have cosponsored these guidelines for preventing opportunistic infections (OIs) among hematopoietic stem cell transplant (HSCT) recipients. The guidelines were drafted with the assistance of a working group of experts in infectious diseases, transplantation, and public health. For the purposes of this report, HSCT is defined as any transplantation of blood- or marrow-derived hematopoietic stem cells, regardless of transplant type (i.e., allogeneic or autologous) or cell source (i.e., bone marrow, peripheral blood, or placental or umbilical cord blood). Such OIs as bacterial, viral, fungal, protozoal, and helminth infections occur with increased frequency or severity among HSCT recipients. These evidence-based guidelines contain information regarding preventing OIs, hospital infection control, strategies for safe living after transplantation, vaccinations, and hematopoietic stem cell safety. The disease-specific sections address preventing exposure and disease for pediatric and adult and autologous and allogeneic HSCT recipients. The goal of these guidelines is twofold: to summarize current data and provide evidence-based recommendations regarding preventing OIs among HSCT patients. The guidelines were developed for use by HSCT recipients, their household and close contacts, transplant and infectious diseases physicians, HSCT center personnel, and public health professionals. For all recommendations, prevention strategies are rated by the strength of the recommendation and the quality of the evidence supporting the recommendation. Adhering to these guidelines should reduce the number and severity of OIs among HSCT recipients.

In 1992, the Institute of Medicine (1) recommended that CDC lead a global effort to detect and control emerging infectious agents. In response, CDC published a plan (2) that outlined national disease prevention priorities, including the development of guidelines for preventing opportunistic infections (OIs) among immunosuppressed persons. During 1995, CDC published guidelines for preventing OIs among persons infected with human immunodeficiency virus (HIV) and revised those guidelines during 1997 and 1999 (3--5). Because of the success of those guidelines, CDC sought to determine the need for expanding OI prevention activities to other immunosuppressed populations. An informal survey of hematology, oncology, and infectious disease specialists at transplant centers and a working group formed by CDC determined that guidelines were needed to help prevent OIs among hematopoietic stem cell transplant (HSCT)* recipients.

The working group defined OIs as infections that occur with increased frequency or severity among HSCT recipients, and they drafted evidence-based recommendations for preventing exposure to and disease caused by bacterial, fungal, viral, protozoal, or helminthic pathogens. During March 1997, the working group presented the first draft of these guidelines at a meeting of representatives from public and private health organizations. After review by that group and other experts, these guidelines were revised and made available during September 1999 for a 45-day public comment period after notification in the Federal Register. Public comments were added when feasible, and the report was approved by CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. The pediatric content of these guidelines has been endorsed also by the American Academy of Pediatrics. The hematopoietic stem cell safety section was endorsed by the International Society of Hematotherapy and Graft Engineering.

The first recommendations presented in this report are followed by recommendations for hospital infection control, strategies for safe living, vaccinations, and hematopoietic stem cell safety. Unless otherwise noted, these recommendations address allogeneic and autologous and pediatric and adult HSCT recipients. Additionally, these recommendations are intended for use by the recipients, their household and other close contacts, transplant and infectious diseases specialists, HSCT center personnel, and public health professionals.

For all recommendations, prevention strategies are rated by the strength of the recommendation (Table 1) and the quality of the evidence (Table 2) supporting the recommendation. The principles of this rating system were developed by the Infectious Disease Society of America and the U.S. Public Health Service for use in the guidelines for preventing OIs among HIV-infected persons (3--6). This rating system allows assessments of recommendations to which adherence is critical.

HSCT is the infusion of hematopoietic stem cells from a donor into a patient who has received chemotherapy, which is usually marrow-ablative. Increasingly, HSCT has been used to treat neoplastic diseases, hematologic disorders, immunodeficiency syndromes, congenital enzyme deficiencies, and autoimmune disorders (e.g., systemic lupus erythematosus or multiple sclerosis) (7--10). Moreover, HSCT has become standard treatment for selected conditions (7,11,12). Data from the International Bone Marrow Transplant Registry and the Autologous Blood and Marrow Transplant Registry indicate that approximately 20,000 HSCTs were performed in North America during 1998 (Statistical Center of the International Bone Marrow Transplant Registry and Autologous Blood and Marrow Transplant Registry, unpublished data, 1998).

HSCTs are classified as either allogeneic or autologous on the basis of the source of the transplanted hematopoietic progenitor cells. Cells used in allogeneic HSCTs are harvested from a donor other than the transplant recipient. Such transplants are the most effective treatment for persons with severe aplastic anemia (13) and offer the only curative therapy for persons with chronic myelogenous leukemia (12). Allogeneic donors might be a blood relative or an unrelated donor. Allogeneic transplants are usually most successful when the donor is a human lymphocyte antigen (HLA)-identical twin or matched sibling. However, for allogeneic candidates who lack such a donor, registry organizations (e.g., the National Marrow Donor Program) maintain computerized databases that store information regarding HLA type from millions of volunteer donors (14--16). Another source of stem cells for allogeneic candidates without an HLA-matched sibling is a mismatched family member (17,18). However, persons who receive allogeneic grafts from donors who are not HLA-matched siblings are at a substantially greater risk for graft-versus-host disease (GVHD) (19). These persons are also at increased risk for suboptimal graft function and delayed immune system recovery (19). To reduce GVHD among allogeneic HSCTs, techniques have been developed to remove T-lymphocytes, the principal effectors of GVHD, from the donor graft. Although the recipients of T-lymphocyte--depleted marrow grafts generally have lower rates of GVHD, they also have greater rates of graft rejection, cytomegalovirus (CMV) infection, invasive fungal infection, and Epstein-Barr virus (EBV)-associated posttransplant lymphoproliferative disease (20).

The patient's own cells are used in an autologous HSCT. Similar to autologous transplants are syngeneic transplants, among whom the HLA-identical twin serves as the donor. Autologous HSCTs are preferred for patients who require high-level or marrow-ablative chemotherapy to eradicate an underlying malignancy but have healthy, undiseased bone marrows. Autologous HSCTs are also preferred when the immunologic antitumor effect of an allograft is not beneficial. Autologous HSCTs are used most frequently to treat breast cancer, non-Hodgkin's lymphoma, and Hodgkin's disease (21). Neither autologous nor syngeneic HSCTs confer a risk for chronic GVHD.

Recently, medical centers have begun to harvest hematopoietic stem cells from placental or umbilical cord blood (UCB) immediately after birth. These harvested cells are used primarily for allogeneic transplants among children. Early results demonstrate that greater degrees of histoincompatibility between donor and recipient might be tolerated without graft rejection or GVHD when UCB hematopoietic cells are used (22--24). However, immune system function after UCB transplants has not been well-studied.

HSCT is also evolving rapidly in other areas. For example, hematopoietic stem cells harvested from the patient's peripheral blood after treatment with hematopoietic colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF or filgastrim] or granulocyte-macrophage colony-stimulating factor [GM-CSF or sargramostim]) are being used increasingly among autologous recipients (25) and are under investigation for use among allogeneic HSCT. Peripheral blood has largely replaced bone marrow as a source of stem cells for autologous recipients. A benefit of harvesting such cells from the donor's peripheral blood instead of bone marrow is that it eliminates the need for general anesthesia associated with bone marrow aspiration.

GVHD is a condition in which the donated cells recognize the recipient's cells as nonself and attack them. Although the use of intravenous immunoglobulin (IVIG) in the routine management of allogeneic patients was common in the past as a means of producing immune modulation among patients with GVHD, this practice has declined because of cost factors (26) and because of the development of other strategies for GVHD prophylaxis (27). For example, use of cyclosporine GVHD prophylaxis has become commonplace since its introduction during the early 1980s. Most frequently, cyclosporine or tacrolimus (FK506) is administered in combination with other immunosuppressive agents (e.g., methotrexate or corticosteroids) (27). Although cyclosporine is effective in preventing GVHD, its use entails greater hazards for infectious complications and relapse of the underlying neoplastic disease for which the transplant was performed.

Although survival rates for certain autologous recipients have improved (28,29), infection remains a leading cause of death among allogeneic transplants and is a major cause of morbidity among autologous HSCTs (29). Researchers from the National Marrow Donor Program reported that, of 462 persons receiving unrelated allogeneic HSCTs during December 1987--November 1990, a total of 66% had died by 1991 (15). Among primary and secondary causes of death, the most common cause was infection, which occurred among 37% of 307 patients (15).**

Despite high morbidity and mortality after HSCT, recipients who survive long-term are likely to enjoy good health. A survey of 798 persons who had received an HSCT before 1985 and who had survived for >5 years after HSCT, determined that 93% were in good health and that 89% had returned to work or school full time (30). In another survey of 125 adults who had survived a mean of 10 years after HSCT, 88% responded that the benefits of transplantation outweighed the side effects (31).

During the first year after an HSCT, recipients typically follow a predictable pattern of immune system deficiency and recovery, which begins with the chemotherapy or radiation therapy (i.e., the conditioning regimen) administered just before the HSCT to treat the underlying disease. Unfortunately, this conditioning regimen also destroys normal hematopoiesis for neutrophils, monocytes, and macrophages and damages mucosal progenitor cells, causing a temporary loss of mucosal barrier integrity. The gastrointestinal tract, which normally contains bacteria, commensal fungi, and other bacteria-carrying sources (e.g., skin or mucosa) becomes a reservoir of potential pathogens. Virtually all HSCT recipients rapidly lose all T- and B-lymphocytes after conditioning, losing immune memory accumulated through a lifetime of exposure to infectious agents, environmental antigens, and vaccines. Because transfer of donor immunity to HSCT recipients is variable and influenced by the timing of antigen exposure among donor and recipient, passively acquired donor immunity cannot be relied upon to provide long-term immunity against infectious diseases among HSCT recipients.

During the first month after HSCT, the major host-defense deficits include impaired phagocytosis and damaged mucocutaneous barriers. Additionally, indwelling intravenous catheters are frequently placed and left in situ for weeks to administer parenteral medications, blood products, and nutritional supplements. These catheters serve as another portal of entry for opportunistic pathogens from organisms colonizing the skin (e.g., . coagulase-negative Staphylococci, Staphylococcus aureus, Candida species, and Enterococci) (32,33).

Engraftment for adults and children is defined as the point at which a patient can maintain a sustained absolute neutrophil count (ANC) of >500/mm3 and sustained platelet count of >20,000, lasting >3 consecutive days without transfusions. Among unrelated allogeneic recipients, engraftment occurs at a median of 22 days after HSCT (range: 6--84 days) (15). In the absence of corticosteroid use, engraftment is associated with the restoration of effective phagocytic function, which results in a decreased risk for bacterial and fungal infections. However, all HSCT recipients and particularly allogeneic recipients, experience an immune system dysfunction for months after engraftment. For example, although allogeneic recipients might have normal total lymphocyte counts within >2 months after HSCT, they have abnormal CD4/CD8 T-cell ratios, reflecting their decreased CD4 and increased CD8 T-cell counts (27). They might also have immunoglobulin G (IgG)2, IgG4, and immunoglobulin A (IgA) deficiencies for months after HSCT and have difficulty switching from immunoglobulin M (IgM) to IgG production after antigen exposure (32). Immune system recovery might be delayed further by CMV infection (34).

During the first >2 months after HSCT, recipients might experience acute GVHD that manifests as skin, gastrointestinal, and liver injury, and is graded on a scale of I--IV (32,35,36). Although autologous or syngeneic recipients might occasionally experience a mild, self-limited illness that is acute GVHD-like (19,37), GVHD occurs primarily among allogeneic recipients, particularly those receiving matched, unrelated donor transplants. GVHD is a substantial risk factor for infection among HSCT recipients because it is associated with a delayed immunologic recovery and prolonged immunodeficiency (19). Additionally, the immunosuppressive agents used for GVHD prophylaxis and treatment might make the HSCT recipient more vulnerable to opportunistic viral and fungal pathogens (38).

Certain patients, particularly adult allogeneic recipients, might also experience chronic GVHD, which is graded as either limited or extensive chronic GVHD (19,39). Chronic GVHD appears similar to autoimmune, connective-tissue disorders (e.g., scleroderma or systemic lupus erythematosus) (40) and is associated with cellular and humoral immunodeficiencies, including macrophage deficiency, impaired neutrophil chemotaxis (41), poor response to vaccination (42--44), and severe mucositis (19). Risk factors for chronic GVHD include increasing age, allogeneic HSCT (particularly those among whom the donor is unrelated or a non-HLA identical family member) (40), and a history of acute GVHD (24,45). Chronic GVHD was first described as occurring >100 days after HSCT but can occur 40 days after HSCT (19). Although allogeneic recipients with chronic GVHD have normal or high total serum immunoglobulin levels (41), they experience long-lasting IgA, IgG, and IgG subclass deficiencies (41,46,47) and poor opsonization and impaired reticuloendothelial function. Consequently, they are at even greater risk for infections (32,39), particularly life-threatening bacterial infections from encapsulated organisms (e.g., Stre. pneumoniae, Ha. influenzae, or Ne. meningitidis). After chronic GVHD resolves, which might take years, cell-mediated and humoral immunity function are gradually restored.

HSCT recipients experience certain infections at different times posttransplant, reflecting the predominant host-defense defect(s) (Figure). Immune system recovery for HSCT recipients takes place in three phases beginning at day 0, the day of transplant. Phase I is the preengraftment phase (<30 days after HSCT); phase II, the postengraftment phase (30--100 days after HSCT); and phase III, the late phase (>100 days after HSCT). Prevention strategies should be based on these three phases and the following information:

Preventing infections among HSCT recipients is preferable to treating infections. How ever, despite recent technologic advances, more research is needed to optimize health outcomes for HSCT recipients. Efforts to improve immune system reconstitution, particularly among allogeneic transplant recipients, and to prevent or resolve the immune dysregulation resulting from donor-recipient histoincompatibility and GVHD remain substantial challenges for preventing recurrent, persistent, or progressive infections among HSCT patients.

Preventing Exposure

Because bacteria are carried on the hands, health-care workers (HCWs) and others in contact with HSCT recipients should routinely follow appropriate hand-washing practices to avoid exposing recipients to bacterial pathogens (AIII).

Preventing Disease

Preventing Early Disease (0--100 Days After HSCT). Routine gut decontamination is not recommended for HSCT candidates (51--53) (DIII). Because of limited data, no recommendations can be made regarding the routine use of antibiotics for bacterial prophylaxis among afebrile, asymptomatic neutropenic recipients. Although studies have reported that using prophylactic antibiotics might reduce bacteremia rates after HSCT (51), infection-related fatality rates are not reduced (52). If physicians choose to use prophylactic antibiotics among asymptomatic, afebrile, neutropenic recipients, they should routinely review hospital and HSCT center antibiotic-susceptibility profiles, particularly when using a single antibiotic for antibacterial prophylaxis (BIII). The emergence of fluoquinolone-resistant coagulase-negative Staphylococci and Es. coli (51,52), vancomycin-intermediate Sta. aureus and vancomycin-resistant Enterococcus (VRE) are increasing concerns (54). Vancomycin should not be used as an agent for routine bacterial prophylaxis (DIII). Growth factors (e.g., GM-CSF and G-CSF) shorten the duration of neutropenia after HSCT (55); however, no data were found that indicate whether growth factors effectively reduce the attack rate of invasive bacterial disease.

Physicians should not routinely administer IVIG products to HSCT recipients for bacterial infection prophylaxis (DII), although IVIG has been recommended for use in producing immune system modulation for GVHD prevention. Researchers have recommended routine IVIG*** use to prevent bacterial infections among the approximately 20%--25% of HSCT recipients with unrelated marrow grafts who experience severe hypogamma-globulinemia (e.g., IgG < 400 mg/dl) within the first 100 days after transplant (CIII). For example, recipients who are hypogammaglobulinemic might receive prophylactic IVIG to prevent bacterial sinopulmonary infections (e.g., from Stre. pneumoniae) (8) (CIII). For hypogammaglobulinemic allogeneic recipients, physicians can use a higher and more frequent dose of IVIG than is standard for non-HSCT recipients because the IVIG half-life among HSCT recipients (generally 1--10 days) is much shorter than the half-life among healthy adults (generally 18--23 days) (56--58). Additionally, infections might accelerate IgG catabolism; therefore, the IVIG dose for a hypogammaglobulinemic recipient should be individualized to maintain trough serum IgG concentrations >400--500 mg/dl (58) (BII). Consequently, physicians should monitor trough serum IgG concentrations among these patients approximately every 2 weeks and adjust IVIG doses as needed (BIII) (Appendix).

Preventing Late Disease (>100 Days After HSCT). Antibiotic prophylaxis is recommended for preventing infection with encapsulated organisms (e.g., Stre. pneumoniae, Ha. influenzae, or Ne. meningitidis) among allogeneic recipients with chronic GVHD for as long as active chronic GVHD treatment is administered (59) (BIII). Antibiotic selection should be guided by local antibiotic resistance patterns. In the absence of severe demonstrable hypogammaglobulinemia (e.g., IgG levels < 400 mg/dl, which might be associated with recurrent sinopulmonary infections), routine monthly IVIG administration to HSCT recipients >90 days after HSCT is not recommended (60) (DI) as a means of preventing bacterial infections.

Other Disease Prevention Recommendations. Routine use of IVIG among autologous recipients is not recommended (61) (DII). Recommendations for preventing bacterial infections are the same among pediatric or adult HSCT recipients.

Preventing Exposure

Appropriate care precautions should be taken with hospitalized patients infected with Stre. pneumoniae (62,63) (BIII) to prevent exposure among HSCT recipients.

Preventing Disease

Information regarding the currently available 23-valent pneumococcal polysaccharide vaccine indicates limited immunogenicity among HSCT recipients. However, because of its potential benefit to certain patients, it should be administered to HSCT recipients at 12 and 24 months after HSCT (64--66) (BIII). No data were found regarding safety and immunogenicity of the 7-valent conjugate pneumococcal vaccine among HSCT recipients; therefore, no recommendation regarding use of this vaccine can be made.

Antibiotic prophylaxis is recommended for preventing infection with encapsulated organisms (e.g., Stre. pneumoniae, Ha. influenzae, and Ne. meningitidis) among allogeneic recipients with chronic GVHD for as long as active chronic GVHD treatment is administered (59) (BIII). Trimethoprim-sulfamethasaxole (TMP-SMZ) administered for Pneumocystis carinii pneumonia (PCP) prophylaxis will also provide protection against pneumococcal infections. However, no data were found to support using TMP-SMZ prophylaxis among HSCT recipients solely for the purpose of preventing Stre. pneumoniae disease. Certain strains of Stre. pneumoniae are resistant to TMP-SMZ and penicillin. Recommendations for preventing pneumococcal infections are the same for allogeneic or autologous recipients.

As with adults, pediatric HSCT recipients aged >2 years should be administered the current 23-valent pneumococcal polysaccharide vaccine because the vaccine can be effective (BIII). However, this vaccine should not be administered to children aged <2 years because it is not effective among that age population (DI). No data were found regarding safety and immunogenicity of the 7-valent conjugate pneumococcal vaccine among pediatric HSCT recipients; therefore, no recommendation regarding use of this vaccine can be made.

Preventing Exposure

Because Streptococci viridans colonize the oropharynx and gut, no effective method of preventing exposure is known.

Preventing Disease

Chemotherapy-induced oral mucositis is a potential source of Streptococci viridans bacteremia. Consequently, before conditioning starts, dental consults should be obtained for all HSCT candidates to assess their state of oral health and to perform any needed dental procedures to decrease the risk for oral infections after transplant (67) (AIII).

Generally, HSCT physicians should not use prophylactic antibiotics to prevent Streptococci viridans infections (DIII). No data were found that demonstrate efficacy of prophylactic antibiotics for this infection. Furthermore, such use might select antibiotic-resistant bacteria, and in fact, penicillin- and vancomycin-resistant strains of Streptococci viridans have been reported (68). However, when Streptococci viridans infections among HSCT recipients are virulent and associated with overwhelming sepsis and shock in an institution, prophylaxis might be evaluated (CIII). Decisions regarding the use of Streptococci viridans prophylaxis should be made only after consultation with the hospital epidemiologists or infection-control practitioners who monitor rates of nosocomial bacteremia and bacterial susceptibility (BIII).

HSCT physicians should be familiar with current antibiotic susceptibilities for patient isolates from their HSCT centers, including Streptococci viridans (BIII). Physicians should maintain a high index of suspicion for this infection among HSCT recipients with symptomatic mucositis because early diagnosis and aggressive therapy are currently the only potential means of preventing shock when severely neutropenic HSCT recipients experience Streptococci viridans bacteremia (69).

Preventing Exposure

Adults with Ha. influenzae type b (Hib) pneumonia require standard precautions (62) to prevent exposing the HSCT recipient to Hib. Adults and children who are in contact with the HSCT recipient and who have known or suspected invasive Hib disease, including meningitis, bacteremia, or epiglottitis, should be placed in droplet precautions until 24 hours after they begin appropriate antibiotic therapy, after which they can be switched to standard precautions. Household contacts exposed to persons with Hib disease and who also have contact with HSCT recipients should be administered rifampin prophylaxis according to published recommendations (70,71); prophylaxis for household contacts of a patient with Hib disease are necessary if all contacts aged <4 years are not fully vaccinated (BIII) (Appendix). This recommendation is critical because the risk for invasive Hib disease among unvaccinated household contacts aged <4 years is increased, and rifampin can be effective in eliminating Hib carriage and preventing invasive Hib disease (72--74). Pediatric household contacts should be up-to-date with Hib vaccinations to prevent possible Hib exposure to the HSCT recipient (AII).

Preventing Disease

Although no data regarding vaccine efficacy among HSCT recipients were found, Hib conjugate vaccine should be administered to HSCT recipients at 12, 14, and 24 months after HSCT (BII). This vaccine is recommended because the majority of HSCT recipients have low levels of Hib capsular polysaccharide antibodies >4 months after HSCT (75), and allogeneic recipients with chronic GVHD are at increased risk for infection from encapsulated organisms (e.g., Hib) (76,77). HSCT recipients who are exposed to persons with Hib disease should be offered rifampin prophylaxis according to published recommendations (70) (BIII) (Appendix).

Antibiotic prophylaxis is recommended for preventing infection with encapsulated organisms (e.g., Stre. pneumoniae, Ha. influenzae, or Ne. meningitidis) among allogeneic recipients with chronic GVHD for as long as active chronic GVHD treatment is administered (59) (BIII). Antibiotic selection should be guided by local antibiotic-resistance patterns. Recommendations for preventing Hib infections are the same for allogeneic or autologous recipients. Recommendations for preventing Hib disease are the same for pediatric or adult HSCT recipients, except that any child infected with Hib pneumonia requires standard precautions with droplet precautions added for the first 24 hours after beginning appropriate antibiotic therapy (62,70) (BIII). Appropriate pediatric doses should be administered for Hib conjugate vaccine and for rifampin prophylaxis (71) (Appendix).

Preventing Exposure

HSCT candidates should be tested for the presence of serum anti-CMV IgG antibodies before transplantation to determine their risk for primary CMV infection and reactivation after HSCT (AIII). Only Food and Drug Administration (FDA) licensed or approved tests should be used. HSCT recipients and candidates should avoid sharing cups, glasses, and eating utensils with others, including family members, to decrease the risk for CMV exposure (BIII).

Sexually active patients who are not in long-term monogamous relationships should always use latex condoms during sexual contact to reduce their risk for exposure to CMV and other sexually transmitted pathogens (AII). However, even long-time monogamous pairs can be discordant for CMV infections. Therefore, during periods of immuno-compromise, sexually active HSCT recipients in monogamous relationships should ask partners to be tested for serum CMV IgG antibody, and discordant couples should use latex condoms during sexual contact to reduce the risk for exposure to this sexually transmitted OI (CIII).

After handling or changing diapers or after wiping oral and nasal secretions, HSCT candidates and recipients should practice regular hand washing to reduce the risk for CMV exposure (AII). CMV-seronegative recipients of allogeneic stem cell transplants from CMV-seronegative donors (i.e., R-negative or D-negative) should receive only leukocyte-reduced or CMV-seronegative red cells or leukocyte-reduced platelets (<1 x 106 leukocytes/unit) to prevent transfusion-associated CMV infection (78) (AI). However, insufficient data were found to recommend use of leukocyte-reduced or CMV-seronega tive red cells and platelets among CMV-seronegative recipients who have CMV-seropositive donors (i.e., R-negative or D-positive).

All HCWs should wear gloves when handling blood products or other potentially contaminated biologic materials (AII) to prevent transmission of CMV to HSCT recipients. HSCT patients who are known to excrete CMV should be placed under standard precautions (62) for the duration of CMV excretion to avoid possible transmission to CMV-seronegative HSCT recipients and candidates (AIII). Physicians are cautioned that CMV excretion can be episodic or prolonged.

Preventing Disease and Disease Recurrence

HSCT recipients at risk for CMV disease after HSCT (i.e., all CMV-seropositive HSCT recipients, and all CMV-seronegative recipients with a CMV-seropositive donor) should be placed on a CMV disease prevention program from the time of engraftment until 100 days after HSCT (i.e., phase II) (AI). Physicians should use either prophylaxis or preemptive treatment with ganciclovir for allogeneic recipients (AI). In selecting a CMV disease prevention strategy, physicians should assess the risks and benefits of each strategy, the needs and condition of the patient, and the hospital's virology laboratory support capability.

Prophylaxis strategy against early CMV (i.e., <100 days after HSCT) for allogeneic recipients involves administering ganciclovir prophylaxis to all allogeneic recipients at risk throughout phase II (i.e., from engraftment to 100 days after HSCT). The induction course is usually started at engraftment (AI), although physicians can add a brief prophylactic course during HSCT preconditioning (CIII) (Appendix).

Preemptive strategy against early CMV (i.e., <100 days after HSCT) for allogeneic recipients is preferred over prophylaxis for CMV-seronegative HSCT recipients of seropositive donor cells (i.e., D-positive or R-negative) because of the low attack rate of active CMV infection if screened or filtered blood product support is used (BII). Preemptive strategy restricts ganciclovir use for those patients who have evidence of CMV infection after HSCT. It requires the use of sensitive and specific laboratory tests to rapidly diagnose CMV infection after HSCT and to enable immediate administration of ganciclovir after CMV infection has been detected. Allogeneic recipients at risk should be screened >1 times/week from 10 days to 100 days after HSCT (i.e., phase II) for the presence of CMV viremia or antigenemia (AIII).

HSCT physicians should select one of two diagnostic tests to determine the need for preemptive treatment. Currently, the detection of CMV pp65 antigen in leukocytes (antigenemia) (79,80) is preferred for screening for preemptive treatment because it is more rapid and sensitive than culture and has good positive predictive value (79--81). Direct detection of CMV-DNA (deoxyribonucleic acid) by polymerase chain reaction (PCR) (82) is very sensitive but has a low positive predictive value (79). Although CMV-DNA PCR is less sensitive than whole blood or leukocyte PCR, plasma CMV-DNA PCR is useful during neutropenia, when the number of leukocytes/slide is too low to allow CMV pp65 antigenemia testing.

Virus culture of urine, saliva, blood, or bronchoalveolar washings by rapid shell-vial culture (83) or routine culture (84,85) can be used; however, viral culture techniques are less sensitive than CMV-DNA PCR or CMV pp65 antigenemia tests. Also, rapid shell-viral cultures require >48 hours and routine viral cultures can require weeks to obtain final results. Thus, viral culture techniques are less satisfactory than PCR or antigenemia tests. HSCT centers without access to PCR or antigenemia tests should use prophylaxis rather than preemptive therapy for CMV disease prevention (86) (BII). Physicians do use other diagnostic tests (e.g., hybrid capture CMV-DNA assay, Version 2.0 [87] or CMV pp67 viral RNA [ribonucleic acid] detection) (88); however, limited data were found regarding use among HSCT recipients, and therefore, no recommendation for use can be made.

Allogeneic recipients <100 days after HSCT (i.e., during phase II) should begin preemptive treatment with ganciclovir if CMV viremia or any antigenemia is detected or if the recipient has >2 consecutively positive CMV-DNA PCR tests (BIII). After preemptive treatment has been started, maintenance ganciclovir is usually continued until 100 days after HSCT or for a minimum of 3 weeks, whichever is longer (AI) (Appendix). Antigen or PCR tests should be negative when ganciclovir is stopped. Studies report that a shorter course of ganciclovir (e.g., for 3 weeks or until negative PCR or antigenemia occurs) (89--91) might provide adequate CMV prevention with less toxicity, but routine weekly screening by pp65 antigen or PCR test is necessary after stopping ganciclovir because CMV reactivation can occur (BIII).

Presently, only the intravenous formulation of ganciclovir has been approved for use in CMV prophylactic or preemptive strategies (BIII). No recommendation for oral ganciclovir use among HSCT recipients can be made because clinical trials evaluating its efficacy are still in progress. One group has used ganciclovir and foscarnet on alternate days for CMV prevention (92), but no recommendation can be made regarding this strategy because of limited data. Patients who are ganciclovir-intolerant should be administered foscarnet instead (93) (BII) (Appendix). HSCT recipients receiving ganciclovir should have ANCs checked >2 times/week (BIII). Researchers report managing ganciclovir-associated neutropenia by adding G-CSF (94) or temporarily stopping ganciclovir for >2 days if the patient's ANC is <1,000 (CIII). Ganciclovir can be restarted when the patient's ANC is >1,000 for 2 consecutive days. Alternatively, researchers report substituting foscarnet for ganciclovir if a) the HSCT recipient is still CMV viremic or antigenemic or b) the ANC remains <1,000 for >5 days after ganciclovir has been stopped (CIII) (Appendix). Because neutropenia accompanying ganciclovir administration is usually brief, such patients do not require antifungal or antibacterial prophylaxis (DIII).

Currently, no benefit has been reported from routinely administering ganciclovir prophylaxis to all HSCT recipients at >100 days after HSCT (i.e., during phase III). However, persons with high risk for late CMV disease should be routinely screened biweekly for evidence of CMV reactivation as long as substantial immunocompromise persists (BIII). Risk factors for late CMV disease include allogeneic HSCT accompanied by chronic GVHD, steroid use, low CD4 counts, delay in high avidity anti-CMV antibody, and recipients of matched unrelated or T-cell--depleted HSCTs who are at high risk (95--99). If CMV is still detectable by routine screening >100 days after HSCT, ganciclovir should be continued until CMV is no longer detectable (AI). If low-grade CMV antigenemia (<5 positive cells/slide) is detected on routine screening, the antigenemia test should be repeated in 3 days (BIII). If CMV antigenemia indicates >5 cells/slide, PCR is positive, or the shell-vial culture detects CMV viremia, a 3-week course of preemptive ganciclovir treatment should be administered (BIII) (Appendix). Ganciclovir should also be started if the patient has had >2 consecutively positive viremia or PCR tests (e.g., in a person receiving steroids for GVHD or who received ganciclovir or foscarnet at <100 days after HSCT). Current investigational strategies for preventing late CMV disease include the use of targeted prophylaxis with antiviral drugs and cellular immunotherapy for those with deficient or absent CMV-specific immune system function.

If viremia persists after 4 weeks of ganciclovir preemptive therapy or if the level of antigenemia continues to rise after 3 weeks of therapy, ganciclovir-resistant CMV should be suspected. If CMV viremia recurs during continuous treatment with ganciclovir, researchers report restarting ganciclovir induction (100) or stopping ganciclovir and starting foscarnet (CIII). Limited data were found regarding the use of foscarnet among HSCT recipients for either CMV prophylaxis or preemptive therapy (92,93).

Infusion of donor-derived CMV-specific clones of CD8+ T-cells into the transplant recipient is being evaluated under FDA Investigational New Drug authorization; therefore, no recommendation can be made. Although, in a substantial cooperative study, high-dose acyclovir has had certain efficacy for preventing CMV disease (101), its utility is limited in a setting where more potent anti-CMV agents (e.g., ganciclovir) are used (102). Acyclovir is not effective in preventing CMV disease after autologous HSCT (103) and is, therefore, not recommended for CMV preemptive therapy (DII). Consequently, valacyclovir, although under study for use among HSCT recipients, is presumed to be less effective than ganciclovir against CMV and is currently not recommended for CMV disease prevention (DII).

Although HSCT physicians continue to use IVIG for immune system modulation, IVIG is not recommended for CMV disease prophylaxis among HSCT recipients (DI). Cidofovir, a nucleoside analog, is approved by FDA for the treatment of AIDS-associated CMV retinitis. The drug's major disadvantage is nephrotoxicity. Cidofovir is currently in FDA phase 1 trial for use among HSCT recipients; therefore, recommendations for its use cannot be made.

Use of CMV-negative or leukocyte-reduced blood products is not routinely required for all autologous recipients because most have a substantially lower risk for CMV disease. However, CMV-negative or leukocyte-reduced blood products can be used for CMV-seronegative autologous recipients (CIII). Researchers report that CMV-seropositive autologous recipients be evaluated for preemptive therapy if they have underlying hematologic malignancies (e.g., lymphoma or leukemia), are receiving intense conditioning regimens or graft manipulation, or have recently received fludarabine or 2-chlorodeoxyadenosine (CDA) (CIII). This subpopulation of autologous recipients should be monitored weekly from time of engraftment until 60 days after HSCT for CMV reactivation, preferably with quantitative CMV pp65 antigen (80) or quantitative PCR (BII).

Autologous recipients at high risk who experience CMV antigenemia (i.e., blood levels of >5 positive cells/slide) should receive 3 weeks of preemptive treatment with ganciclovir or foscarnet (80), but CD34+-selected patients should be treated at any level of antigenemia (BII) (Appendix). Prophylactic approach to CMV disease prevention is not appropriate for CMV-seropositive autologous recipients. Indications for the use of CMV prophylaxis or preemptive treatment are the same for children or adults.

Preventing Exposure

All transplant candidates, particularly those who are EBV-seronegative, should be advised of behaviors that could decrease the likelihood of EBV exposure (AII). For example, HSCT recipients and candidates should follow safe hygiene practices (e.g., frequent hand washing [AIII] and avoiding the sharing of cups, glasses, and eating utensils with others) (104) (BIII), and they should avoid contact with potentially infected respiratory secretions and saliva (104) (AII).

Preventing Disease

Infusion of donor-derived, EBV-specific cytotoxic T-lymphocytes has demonstrated promise in the prophylaxis of EBV-lymphoma among recipients of T-cell--depleted unrelated or mismatched allogeneic recipients (105,106). However, insufficient data were found to recommend its use. Prophylaxis or preemptive therapy with acyclovir is not recommended because of lack of efficacy (107,108) (DII).

Preventing Exposure

HSCT candidates should be tested for serum anti-HSV IgG before transplant (AIII); however, type-specific anti-HSV IgG serology testing is not necessary. Only FDA-licensed or -approved tests should be used. All HSCT candidates, particularly those who are HSV-seronegative, should be informed of the importance of avoiding HSV infection while immunocompromised and should be advised of behaviors that will decrease the likelihood of HSV exposure (AII). HSCT recipients and candidates should avoid sharing cups, glasses, and eating utensils with others (BIII). Sexually active patients who are not in a long-term monogamous relationship should always use latex condoms during sexual contact to reduce the risk for exposure to HSV as well as other sexually transmitted pathogens (AII). However, even long-time monogamous pairs can be discordant for HSV infections. Therefore, during periods of immunocompromise, sexually active HSCT recipients in such relationships should ask partners to be tested for serum HSV IgG antibody. If the partners are discordant, they should consider using latex condoms during sexual contact to reduce the risk for exposure to this sexually transmitted OI (CIII). Any person with disseminated, primary, or severe mucocutaneous HSV disease should be placed under contact precautions for the duration of the illness (62) (AI) to prevent transmission of HSV to HSCT recipients.

Preventing Disease and Disease Recurrence

Acyclovir. Acyclovir prophylaxis should be offered to all HSV-seropositive allogeneic recipients to prevent HSV reactivation during the early posttransplant period (109--113) (AI). Standard approach is to begin acyclovir prophylaxis at the start of the conditioning therapy and continue until engraftment occurs or until mucositis resolves, whichever is longer, or approximately 30 days after HSCT (BIII) (Appendix). Without supportive data from controlled studies, routine use of antiviral prophylaxis for >30 days after HSCT to prevent HSV is not recommended (DIII). Routine acyclovir prophylaxis is not indicated for HSV-seronegative HSCT recipients, even if the donors are HSV-seropositive (DIII). Researchers have proposed administration of ganciclovir prophylaxis alone (86) to HSCT recipients who required simultaneous prophylaxis for CMV and HSV after HSCT (CIII) because ganciclovir has in vitro activity against CMV and HSV 1 and 2 (114), although ganciclovir has not been approved for use against HSV.

Valacyclovir. Researchers have reported valacyclovir use for preventing HSV among HSCT recipients (CIII); however, preliminary data demonstrate that very high doses of valacyclovir (8 g/day) were associated with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome among HSCT recipients (115). Controlled trial data among HSCT recipients are limited (115), and the FDA has not approved valacyclovir for use among recipients. Physicians wishing to use valacyclovir among recipients with renal impairment should exercise caution and decrease doses as needed (BIII) (Appendix).

Foscarnet. Because of its substantial renal and infusion-related toxicity, foscarnet is not recommended for routine HSV prophylaxis among HSCT recipients (DIII).

Famciclovir. Presently, data regarding safety and efficacy of famciclovir among HSCT recipients are limited; therefore, no recommendations for HSV prophylaxis with famciclovir can be made.

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Sickle cell disease affects the hepatobiliary system in different ways at different ages. Intrinsic disease results from recurrent ischemia and bilirubin stones. These result from the vascular obstruction and red cell hemolysis of sickle cell. Biliary sludge is a common finding that is often clinically unimportant. Viral infections that affect the liver may be independent of or secondary to red cell transfusions. The iron overload that accompanies red cell transfusions can lead to liver dysfunction and fibrosis. Many medications taken by sickle cell patients may cause or worsen hepatobiliary disease. The dysfunction of the liver can affect the lungs, kidneys, and coagulation systems. Treatment is directed at the etiology of the dysfunction as well as the underlying sickle cell disease.

The natural consequences of any hemolytic condition affect both the gallbladder [45] and the liver [46]. The gallbladder is affected by hemoglobin (pigmented) stones [47], biliary sludge [4850], and obstruction [5153]. The liver is affected by vasoocclusive changes (right upper quadrant syndrome) of recurrent ischemia and reperfusion injuries [46, 54], iron overload from transfusions that are used to treat both symptomatic anemia and the complications of sickle cell disease [5559], vascular endothelial dysfunction [60], and the liver consequences of the hypercoagulation of sickle cell [6163].

The challenge physicians caring for sickle cell patients is recognizing the life-threatening course from the more frequent, similar appearing milder, recurrent syndromes. A useful way to consider the protean effects of hepatobiliary issues in sickle cell is to consider the disorders of the presentation and evaluation of abdominal complaints of sickle cell followed by a review of the major disorders. Although hepatobiliary conditions are intimately linked, the embryology of the biliary system and the hepatic system shows these two organs to be histologically and functionally separate [64]. This explains the differential response of these organs to the same insult. However, many conditions may overlap, so a single diagnosis may mask parallel processes.

Acute pain in the right upper quadrant is common in sickle cell patients [6567]. The symptom of hepatobiliary disease often must be separated from the more common symptoms of sickle cell disease. Patients develop sickle cell attacks in a consistent pattern. The patient can often recognize whether the current attack is different from prior sickle cell pains. If the pain is new, especially when accompanied by more jaundice than usual, nausea and vomiting, then further hepatobiliary workup is needed. Increasing nausea and vomiting with food points to the gallbladder. Colic pains point to the gallbladder. Right upper quadrant fullness with dull pains points to the liver. General jaundice points to both.

The liver is often increased in size throughout the life of the patient [68]. If the liver has acutely increased in size, then hepatic congestion or sequestration may be involved. A 1980 clinicopathologic study of 70 autopsies of sickle cell patients found 91% with enlarged livers characterized by distention of Kupffer cells engorged with red cells [69]. In 27% the liver sinusoids were distended with obstruction from sickled red cells. Focal necrosis of liver tissue was present in 34%. 20% of patients had reparative liver changes of portal fibrosis and regenerative nodules. The authors felt that recurrent vascular obstruction, ischemia, necrosis, and repair best explained the pathological findings.

If right upper quadrant pain is severe, then acute swelling or inflammation may be involved. Murphy's sign is often lost in the general pains but, if present, may point to the gallbladder. If the serum bilirubin concentration is over 4mg/dL, then checking whether the fraction of direct bilirubin exceeds 10% would point to the gallbladder as the source of the increase [70, 71]. Some patients have genetic variations in the UDP glucuronyltransferase that will elevate the serum bilirubin concentration [72]. This recurrent or chronic elevation should be evident on review of the patient's records. In most sickle cell presentations the AST is relatively more elevated that the ALT, as the AST also reflects the degree of hemolysis [73]. If the ALT is similarly elevated as the AST, then a hepatocellular process may be occurring. Similarly the alkaline phosphatase will be elevated in biliary disease. However, bone infarcts will also call the alkaline phosphatase to rise. Fractionating the alkaline phosphatase into bone and biliary sources is seldom done. The clinical presentation usually finds bone pain or severe extremity pains with infarcts, and severe right upper quadrant pains prompt imaging, usually ultrasound, of the hepatobiliary system. Measurement of the aPPT and PT may provide evidence of a more severe process beginning.

Initial evaluation is for conditions that need emergent transfusions or treatments.

Pain patterns that differ from a patient's usual pattern need close evaluation.

Having sickle cell does not protect a patient from any other condition.

Hepatic crisis is often used as a general term to describe right upper quadrant pain in a sickle cell patient [80, 81]. However, hepatic crisis is best used to describe a syndrome consisting of pain, elevated ALT (usually less than 300IU/liter), and hepatic enlargement. Another working definition of a hepatic crisis could be painful hepatomegaly and worsened jaundice (usually less than 12mg/dL) [82]. The definition used causes the incidence of this condition to vary in reports. Large series reports that up to 10% of patients admitted to hospital have hepatic involvement rising to their definition of crisis. Other studies with more restrictive definitions concluded hepatic crisis was rare. The rapidity of the onset of symptoms and the rapidity of the correction of ALT may be able to guide therapy. Symptoms that began suddenly are more often typical, self-limited sickle cell conditions. Symptoms that begin over several days to weeks may be from more severe conditions such as viral or autoimmune hepatitis, liver infarct, or gallbladder dysfunction. Severe elevations of bilirubin (over 30mg/dL) may represent acute liver failure of intrahepatic cholestasis (see below).

If the condition is from typical sickle vaso-occlusion and inflammation, then the elevation of ALT decreases after a few days. Severe, persistent elevations may relate to hepatic infarct, characterized by a wedge-shaped, hypointense CT lesions [83]. Hepatic abscess has been rarely reported, but should be suspected in a patient with fever, a course different from their usual sickle cell crisis, right upper quadrant pain, and tender hepatomegaly [8488]. Hepatic ultrasound would delineate the abscess. Prior areas of hepatic infarction give the bacteria a site to invade. Bacteroides species were found in one report [85]. Bilirubin levels decrease to prior values in about two weeks; liver transaminases return to prior values in about three months. If changes persist beyond those times, further evaluation is needed.

Hepatic sequestration is best diagnosed by a rapid enlargement of the liver with a concurrent drop in hemoglobin concentration [8991]. The bilirubin also will be elevated with a high percentage of direct bilirubin. Transfusions, simple or exchange, may help reserve the process. Hepatic sequestration may be a life-threatening event in pediatric patients with sickle cell disease [8991]. Small vessel congestion with red cells leads to a drop in hemoglobin levels. The liver enlarges and becomes tender and inflamed. Treatment is transfusions. Often the hemoglobin level is low enough that given red cell units (matched for ABO, Kell, E, and C antigens) to raise the hemoglobin to 9g/dL often stabilize the process. Manual or automatic red cell exchanges are indicated for more severe cases shown by hepatic dysfunction or a hemoglobin level over 9 to start with. Hepatic sequestration may be part of the multiorgan failure syndromes [74, 75].

Chronic hepatic sequestration has been reported in a 17-year old with SS hemoglobin [92]. After exchange transfusions, his liver size decreased. However it recurred. This recurrence was successfully treated with hydroxyurea for several months.

One report of reverse sequestration occurred following simple transfusions. This syndrome comprises a sudden increase in hemoglobin concentration, sudden onset of hypertension, acute congestive heart failure, neurologic signs of infarct or hemorrhage [93].

Autoimmune hepatitis is reported in sickle cell patients [94, 95]. Interestingly, it also appears in mice models of sickle cell disease (personal communication). We have documented transient positivity of antibodies to smooth muscle (antiactin F). Associated features of autoimmune hepatitis include rashes, skin ulcers, and joint disease. The etiology, natural course, and treatment of autoimmune hepatitis in sickle cell patients are unclear. If a patient has persistent liver symptoms and antibody titers to smooth muscles, then a therapeutic trial of prednisone and azathioprine may be warranted. Referral to a hepatologist is indicated.

Viral hepatitis occurs at least as frequently as in the general population [96]. Hepatitis C, and to a lesser extent, Hepatitis B, occurred more often because of blood product exposure. Improved blood product testing has reduced the incidence of these infections, but they still occur. We screen all our patients yearly for Hepatitis C viral RNA by PCR. In new patients, persistently elevated ALT levels require screening for viral hepatitis. Every sickle cell patient should be vaccinated with two doses of Hepatitis A vaccine from six months to a year apart and three doses of Hepatitis B vaccinations at zero, one, and six months. Quantitative hepatitis B surface antibody tests and total Hepatitis A antibody tests are available to help decide if a patient has been adequately vaccinated if the records are not available. Many practitioners opt to revaccinate in case of any doubt. No vaccine exists for Hepatitis C prevention. Patients with chronic Hepatitis B and Hepatitis C should be treated as any other patients. There has been some concern about using ribavirin because it may cause hemolytic anemia. If a patient on ribavirin does develop worsening anemia, then placing the patient on monthly transfusions would both allow therapy to continue and would decrease sickle cell and anemia symptoms. A recent article showed good results in treating sickle cell patients for chronic hepatitis C [97]. Liver transplants are as successful in patients with sickle cell disease and other patients needing allographic livers [98101].

Hepatic siderosis is a growing area of concern and research [102]. As red cell transfusions become routine for more indications, the inevitable result is the accumulation of liver iron. After about a year of transfusion therapy, serum ferritin levels rise to over 1,000ng/mL. While serum ferritin is a rough guide to total liver iron, values over 1,000 indicate liver iron overload. Other studies have shown significant liver iron accumulation after 13 units of red cells. Each unit of red cells contains nearly a year worth of dietary iron. Over many years, hepatic dysfunction, insufficiency, fibrosis, and cirrhosis may lead to morbidity and even liver death. Many patients on regular transfusions will have hyperintense livers on CT scans or hypointense livers on MRI scanning [103, 104]. These changes have been used to semiquantitate the degree of iron loading. Chelation with deferoxamine [55, 105], deferasirox [106], or deferiprone (recently approved in the US) does reduce total body iron. However, all regimes have issues with compliance and side effects that require appropriate monitoring. When patients with iron overload are admitted to hospital with noninfectious complaints, we often give deferoxamine 3 grams in 500mL normal saline intravenously over 24 hours, repeating continuously during their stay. Giving Vitamin C 250mg orally daily while the patient is on deferoxamine increases iron excretion [107, 108]. Ongoing cohort studies should help define the natural history of iron overload in sickle cell patients [109111].

Hepatic effects on kidneys and lungs are increasingly recognized. Although there are few publications concerning sickle cell patients, such effects are well known in other conditions where the liver is cirrhotic or dysfunctional. The hepatorenal syndrome [112], hepatopulmonary syndrome [113], and the portopulmonary [114] syndrome may complicate the hepatic disease of sickle cell.

Sickle cell intrahepatic cholestasis or sickle cell hepatopathy is a condition with marked hyperbilirubinemia (>50mg/dL) and a high fraction of direct (conjugated) bilirubin (about 50%) [77, 115118]. Other features of right upper quadrant pain and progressive hepatomegaly resemble many of the hepatic crisis syndromes. However, in sickle cell intrahepatic cholestasis, the liver transaminases are nearly at baseline. Coagulopathy as assessed by the PT test is often found. Renal insufficiency is often present, likely from the nephrotoxic effects of bilirubin. Endoscope retrograde cholangiopancreatography has been reported to guide management by diagnosing strictures from ischemic cholangiopathy and defining the presence or absence of common bile duct stones [119]. Some authors consider the presence of acute sickle hepatopathy to contraindicate liver biopsies [120]. Ischemic cholangiopathy has also been described [121].

Early reports indicate that sickle cell intrahepatic cholestasis was a life-threatening condition that mandated exchange transfusions. As clinicians were more aware of the condition, series were reported that had a less severe course [122]. Given the protean causes of intrahepatic cholestasis, it is reasonable to divide cases of cholestasis into those with and those without other evidence of marked hepatic dysfunction and coagulopathy. The milder cases (bilirubin level 10 to 30mg/dL) appear to be more common in children. Patients in the first category should be monitored for worsening hepatic function: encephalopathy, coagulopathy, and rising bilirubin concentrations. For the more severe cases, exchange transfusion may be given, but it is not always effective [77, 79].

Cholelithiasis occurs as early as two years old [47]. About 30% of patients will have gallstones by 18 years of age [52, 123, 124]. The incidence and prevalence of this condition appears to be affected by local diet and possible genetic factors [125]. The coinheritance of -thalassemia may reduce the incidence of stones since it may lessen the degree of hemolysis that is thought to drive stone formation [126]. The cause of cholelithiasis is usually pigmented stones resulting from the breakdown of hemoglobin [45]. Some reports implicate ceftriaxone and other third generation cephalosporins as causing crystallization in the gallbladder [127]. However, these antibiotics are commonly and usefully used in the proper settings. In adults, asymptomatic gallstones are common and are best treated by observation only [52, 53, 68, 123]. Abdominal and right upper quadrant pains are common in sickle cell patients. Cholecystectomy for recurrent right upper quadrant pains often does not relieve the recurrent symptoms. Only if signs of cholecystitis (fever, increased direct bilirubin, and positive imaging) develop, should cholecystectomy be considered after the treatment with supportive care and antibiotics [47, 124]. Laparoscopic cholecystectomy is the procedure of choice for this indication [128, 129]. This also causes less abdominal muscle disruption and decreases postsurgical complications including acute chest syndrome. Ultrasound is the imaging of choice but is not diagnostic in most cases. Reports of pancreatitis from sickling also exist. Biliary scintigraphy is seldom used because of the numerous false positive results [130, 131]. Still, it has a useful negative predictive value if used in the right setting. Technetium scanning may show hyperemia of cholecystitis but its use is not well studied. Liver peliosis and extramedullary erythropoiesis have occasionally been noted as multiple nodules on liver imaging [132].

Biliary sludge is a common finding in sickle cell patients [48, 50]. Biliary sludge is nonshadowing, echogenic intraluminal sediment. This material is calcium bilirubinate, cholesterol crystals, viscous bile, mucus, and proteins. The natural history of biliary sludge in children with sickle cell disease finds that at a mean of 2.1 years of followup, about 65% of such patients do eventually develop gallstones, although not necessarily symptomatic ones. About 40% of patients originally with biliary sludge do not develop gallstones, despite the continued presence of sludge in most [133]. Most authors recommend yearly ultrasounds to access stone formation. They reserve cholecystectomy only for patients with signs and symptoms of acute cholecystitis [133].

Choledocholithiasis also occurs in sickle cell disease [51]. Even in patients with cholecystectomy, recurrent stones may form in the common bile ducts. Symptoms are similar to primary gallbladder disease. Ultrasound may be the best modality to evaluate the common bile duct. Duct obstruction is seldom complete. This may be because pigmented stones are smaller than nonpigmented stones. If the common duct is obstructed, then symptomatic or chemical pancreatitis may be the presentation [134]. After cholecystectomy, the common bile duct is usually dilated, confounding diagnosis of new stones. Given the prevalence of common duct stones, patients with persistent cholestatic jaundice should have imaging to evaluate the ductal system. If surgery is contemplated, some authors suggest ERCP as the best approach to determine management [135].

Acute cholecystitis presents as it does in patients without sickle cell disease [53, 136]. Right upper quadrant pain, fever, nausea, and vomiting have a long and diverse differential diagnosis. When the diagnosis is suspected, then ultrasound is the usual next step. Imaging signs of acute inflammation or obstructing stones prompt treatment for pain, hydration, and the assessment for infection. Laparoscopic cholecystectomy is deferred until the acute episode is over. If all the stones and sludge have cleared, then surgery may not be indicated. Some authors prefer a conservative approach. Intraoperative cholangiography is reported to have a 25% false positive rate. Some authors recommend intraoperative ERCP. A detailed intraoperative evaluation of the biliary system is important as symptoms often persist or recur after cholecystectomy [124].

Chronic cholecystitis may be related to persistent gallstones or persistent biliary sludge. Recurrent symptoms consistent with colic warrant screening with blood work and imaging. If the blood work shows increases in conjugated (direct) bilirubin during the attacks, and there are ultrasonographic signs of a thickened gallbladder wall, then cholecystectomy may decrease these symptoms. However, just as in chronic cholecystitis in the general population, the symptoms may recur several months after surgery.

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