Fanconi anaemia (FA) is a cancer‐prone genetic disorder that is characterised by cytogenetic instability and redox abnormalities. Although rare subtypes of FA (B, D1 and D2) have been implicated in DNA repair through links with BRCA1 and BRCA2, such a role has yet to be demonstrated for gene products of the common subtypes. Instead, these products have been strongly implicated in xenobiotic metabolism and redox homeostasis through interactions of FANCC with cytochrome P‐450 reductase and with glutathione S‐transferase, and of FANCG (...) with cytochrome P‐450 2E1, as well as redox‐dependent signalling through an interaction between FANCA and Akt kinase. We hypothesise that FA proteins act directly (via FANCC and FANCG) and indirectly (via FANCA, BRCA2 and FANCD2) with the machinery of cellular defence to modulate oxidative stress. The latter interactions may co‐ordinate the link between the response to DNA damage and oxidative stress parameters (3, 6–12). BioEssays 25:589–595, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

The concept of quality of life is the basis for a new paradigm of clinical medicine. Its assessment is considered to be an important instrument in determining disease severity and effectiveness of different treatment modalities. Our studies are devoted to the problem of diabetes complications especially anemia in patients with diabetic kidney disease. Anemia in subjects with diabetic nephropathy may result from various pathogenic factors including erythropoietin deficiency, iron deficiency, vitamin B12 and/or folate deficiencies, the effects of proinflammatory (...) cytokines etc. Diabetic patients with anemia are at increased risk of cardiovascular accidents and death. The aim of this study was to assess the influence of anemia on the quality of life of patients with early stages of diabetic nephropathy. We investigated 127 patients with type 2 diabetes mellitus and early diabetic nephropathy. Anemia was defined according to the World Health Organization criteria. Anemic patients were divided into three groups according to the stage of chronic kidney disease. Patients’ quality of life was assessed with SF-36 health survey. Anemic patients had lower scores of physical role functioning and emotional role functioning as compared to the patients with normal hemoglobin level, irrespective of the stage of chronic kidney disease. Patients with anemia and chronic kidney disease stage 3 had lower scores of general health perceptions, physical functioning, bodily pain, vitality and mental health than patients in the non-anemic group. Social role functioning was similar in anemic and non-anemic patients. The possible mechanisms and implications of the above mentioned findings are discussed with a medical and humanitarian perspective. The directions of further studies are proposed. (shrink)

Fanconi anaemia (FA) comprises a group of autosomal recessive disorders resulting from mutations in one of eight genes (FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF and FANCG). Although caused by relatively simple mutations, the disease shows a complex phenotype, with a variety of features including developmental abnormalities and ultimately severe anaemia and/or leukemia leading to death in the mid teens. Since 1992 all but two of the genes have been identified, and molecular analysis of their products has revealed a complex (...) mode of action. Many of the proteins form a nuclear multisubunit complex that appears to be involved in the repair of double‐strand DNA breaks. Additionally, at least one of the proteins, FANCC, influences apoptotic pathways in response to oxidative damage. Further analysis of the FANC proteins will provide vital information on normal cell responses to damage and allow therapeutic strategies to be developed that will hopefully supplant bone marrow transplantation. BioEssays 24:439–448, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

The autosomal recessive genetic disease, Fanconi anaemia, is perceived as another manifestation of defective cellular DNA repair, just as in the autosomal recessive disease Xeroderma pigmentosum. The biochemistry and cellular biology of Xeroderma pigmentosum have been convincingly elucidated, but the same has not been true for Fanconi anaemia. In this review we consider the pleiotropic nature of Fanconi anaemia, its clinical and cellular variability and its genetic heterogeneity. We take into account the wealth of experimental findings available and offer a (...) novel hypothesis involving feedback control of DNA replication during S phase of the cell cycle to explain the basic defect in the disease. (shrink)

Fanconi anemia (FA) is generally classified as a DNA repair disorder, conferring a genetic predisposition to cancer and prominent bone marrow failure (BMF) in early childhood. Corroborative human and murine studies point to a fetal origin of hematopoietic stem cell (HSC) attrition under replicative stress. Along with intriguing recent insights into non‐canonical roles and domain‐specific functions of FA proteins, these studies have raised the possibility of a DNA repair‐independent BMF etiology. However, deeper mechanistic insight is critical as current curative (...) options of allogeneic stem cell transplantation and emerging gene therapy have limited eligibility, carry significant side effects, and involve complex procedures restricted to resource‐rich environments. To develop rational and broadly accessible therapies for FA patients, the field will need more faithful disease models that overcome the scarcity of patient samples, leverage technological advances, and adopt investigational clinical trial designs tailored for rare diseases. (shrink)

In his (1988), Brian Baigrie criticizes my earlier discussion of the rationality of science (Siegel 1985). In this response, I argue that (1) Baigrie misses the point of my tripartite distinction between different questions one can ask about science's rationality, (2) Baigrie's argument that the history of the development of methodological principles is crucial to philosophical discussion of the rationality of science is flawed, and (3) Baigrie's charge that my view is "anemic" rests on a failure to appreciate the point (...) of my tripartite distinction. (shrink)

"Dying in the City of Blues: Sickle Cell Anemia and the Politics of Race and Health" by Keith Wailoo is reviewed.

A case study concerning a 27-year-old African American female with sickle cell anemia who requests specific medication is presented. Hospital team members should do their best to treat the patient and form their judgments based on her clinical data and medical and social history.

Na doença falciforme, o genótipo HbSS da anemia falciforme, considerado a forma mais grave, prevalente no continente africano, tem alta morbidade e mortalidade. Objetivo: identificar se a estrutura instalada na atenção às pessoas com anemia falciforme e seus familiares, contribui para a redução da mortalidade precoce em Angola. Material e Método: pesquisa exploratória descritiva, realizada em Luanda-Angola, no período entre agosto e dezembro de 2022. Foram aplicados questionários estruturados para 20 pessoas com doença falciforme e 15 familiares, todos (...) com mais de 21 anos. A metodologia utilizada foi bola de neve. Para análise e discussão dos dados, foi utilizado o referencial teórico de Donabedian, com ênfase no eixo estrutura. Resultados: diagnóstico feito por sinais e sintomas, idade do diagnóstico entre 1 e 5 anos. A crise de dor predominou entre eventos agudos. Conclusão: inexistência de estrutura instalada de saúde em Luanda que garantam no serviço público gratuito o acesso à medicamentos, transfusão de sangue, vacinas especiais e exames complementares. A transferência de tecnologias sociais da organização de sociedade civil brasileira para a de Luanda mostra ser adequada. (shrink)

Sickle cell anemia is a disease characterized by abnormal hemoglobin structure. There is a mutation in the beta-globin gene that changes the sixth amino acid from glutamic acid to valine causing the mutated hemoglobin to polymerize reversibly when deoxygenated to form a gelatinous network of fibrous polymers that stiffen and distort the red blood cell membrane. This leads to episodes of microvascular vasoocclusion and premature RBC destruction leading to hemolytic anemia. For reasons that are unclear, some children develop (...) a large artery vasculopathy involving the intracranial arteries supplying the brain.The risk of stroke for a child with SCD is many times greater than that of a healthy child without SCD or heart disease. There is a technique that allows the identification of the children with SCD who have high risk even within this relatively high-risk group. And there is a highly effective preventive treatment. (shrink)

A high percent of oxidative energy metabolism is needed to support brain growth during infancy. Unhealthy diets and limited nutrition, as well as other environmental insults, can compromise these essential developmental processes. In particular, iron deficiency anemia has been found to undermine both normal brain growth and neurobehavioral development. Even moderate ID may affect neural maturation because when iron is limited, it is prioritized first to red blood cells over the brain. A primate model was used to investigate the (...) neural effects of a transient ID and if deficits would persist after iron treatment. The large size and postnatal growth of the monkey brain makes the findings relevant to the metabolic and iron needs of human infants, and initiating treatment upon diagnosis of anemia reflects clinical practice. Specifically, this analysis determined whether brain maturation would still be compromised at 1 year of age if an anemic infant was treated promptly once diagnosed. The hematology and iron status of 41 infant rhesus monkeys was screened at 2-month intervals. Fifteen became ID; 12 met clinical criteria for anemia and were administered iron dextran and B vitamins for 1–2 months. MRI scans were acquired at 1 year. The volumetric and diffusion tensor imaging measures from the ID infants were compared with monkeys who remained continuously iron sufficient. A prior history of ID was associated with smaller total brain volumes, driven primarily by significantly less total gray matter and smaller GM volumes in several cortical regions. At the macrostructual level, the effect on white matter volumes was not as overt. However, DTI analyses of WM microstructure indicated two later-maturating anterior tracts were negatively affected. The findings reaffirm the importance of iron for normal brain development. Given that brain differences were still evident even after iron treatment and following recovery of iron-dependent hematological indices, the results highlight the importance of early detection and preemptive supplementation to limit the neural consequences of ID. (shrink)

A natural heme deficiency that exists in cells outside of the circulation broadly compromises the heme contents and functions of heme proteins in cells and tissues. Recently, we found that the signaling molecule, nitric oxide (NO), can trigger or repress the deployment of intracellular heme in a concentration‐dependent hormetic manner. This uncovers a new role for NO and sets the stage for it to shape numerous biological processes by controlling heme deployment and consequent heme protein functions in biology.

Sickle cell anemia (SCA) is a major genetic disease with the greatest burden in sub-Saharan Africa. To try to help reduce this burden, some churches in Nigeria conduct premarital sickle cell hemoglobin screening and refuse to conduct weddings when both individuals are identified as carriers of sickle cell trait. This paper explores the ethical challenges involved in such denials. We assess whether churches have the right to decline to marry adults who understand the risks and still prefer to get (...) married, and whether couples should be denied church weddings based on the risk that their child may suffer from sickle cell anemia. We examine the moral and ethical dimensions of such denials and explore the underlying socio-cultural context involving the purpose of marriage and the meaning of the wedding ceremony in societies where premarital screening is one of the few tools available to reduce the risk of having children with SCA. The potential role of the church is also examined against the background of church beliefs, the duty of the church to its members and its role in reducing the suffering of its members and /or their children. We argue that the church should impose these burdens on couples only if doing so promotes a sufficiently compelling goal and there is no less burdensome way to achieve it. We then argue that the goal of reducing the number of individuals in Nigeria who have SCA is compelling. However, testing earlier in life offers a less burdensome and potentially even more effective means of achieving this goal. This suggests that, advocating for earlier screening and helping to support these programs, would likely better promote the church’s own goals of helping its parishioners, increasing the number of church weddings, and reducing the burden of SCA in Nigeria. (shrink)

What is considered normal determines clinical practice in medicine and has implications at an individual level, doctor-patient relationship and health care policies. With the increase in medical information and technical abilities it is urgent to have a clear concept of normality in medicine so that crucial discussions can be held with unequivocal terms.The different meanings for normality were analyzed throughout the literature and grouped according to their relevance in the academic community in models, namely the Biostatistical Theory (BST), Health, Ideal, (...) Process and Biological advantage. The BST is the most established naturalistic approach, however normal variability can arguably constitute a problem. Health is similar and raises the question of setting the boundaries of pathology. Normality as an Ideal is an useful tool but is naturally unrealistic. As a Process it is comprehensible but is hard to frame for practical purposes. If considered as a Biological Advantage, seems intuitive but abnormality should tend to disappear.After, three examples were presented to discuss these models. They were Anemia, Psychiatric diseases and Psychopathy. In the case of Anemia the BST was applied and the arbitrary boundaries but with social impact were exposed. Psychiatric diseases was discussed under the process of self-organization and non-suffering ideal. With Psychopathy the boundaries of biological advantage are questioned.This review appeals to the importance of redesigning of the concept of normality in medicine according to current times and stresses the importance of integrating concepts such as variability and autonomy. (shrink)

Many ethical concerns surrounding human genetics studies remain unresolved. We report here the situation in Cameroon.Objectives: To describe the profile of human genetic studies that used Cameroonian DNA samples, with specific focus on i) the research centres that were involved, ii) authorship, iii) population studied, iv) research topics and v) ethics disclosure, with the aim of raising ethical issues that emerged from these studies.Method: Bibliometric Studies; we conducted a PubMed-based systematic review of all the studies on human genetics that used (...) Cameroonian DNA samples from 1989 to 2009.Results and Discussion: Fifty articles were identified, involving predominantly research centres from Europe (64%) and America (32%). Only 7 (14%) Cameroonian institutions and 14 (28%) Cameroonian authors were associated with these publications.At least 52% of publications were devoted to population genetics (variation/migration patterns) amongst 30 Cameroonian ethnic groups. Very few studies concerned public health related genetic issues and only 5 (10%) references were found for hemoglobinopathies like sickle cell anaemia. Almost all DNA samples are ‘banked’ outside of the African continent.Capacity building, rights to the genetic information and benefits to the individuals, communities and populations who contribute to these studies are addressed.Conclusions: 1) Our data suggests the need for a wider debate towards building capacity and addressing ethical issues related to human genomic research in sub-Saharan Africa and specifically in Cameroon; 2) National ethical guidelines and regulations concerning the collection, use and storage of human DNA are urgently needed in Cameroon. (shrink)

A fourteen year old is diagnosed with aplastic anemia. The teen and his parents are Jehovah’s Witnesses. An ethics consult is called on the day of admission by an ethically sophisticated social worker and attending. The patient and his parents see this diagnosis as “a test of their faith.” The ethical analysis focuses on the mature minor doctrine, i.e. whether the teen has the capacity to make this decision. The hospital chooses to take the case to court, with a (...) result that is at odds with the ethics consultation recommendations. Ethics was never deposed or otherwise invited to be involved with the hearing. Thus the larger question of the relation of ethics and law was brought into stark relief. (shrink)

Common monogenic genetic diseases, ones that have unexpectedly high frequencies in certain populations, have attracted a great number of conflicting evolutionary explanations. This paper will attempt to explain the mystery of why two particularly extensively studied common genetic diseases, Tay Sachs disease and cystic fibrosis, remain evolutionary mysteries despite decades of research. I review the most commonly cited evolutionary processes used to explain common genetic diseases: reproductive compensation, random genetic drift (in the context of founder effect), and especially heterozygote advantage. (...) The latter process has drawn a particularly large amount of attention, having so successfully explained the elevated frequency of sickle cell anemia in malaria-endemic areas. However, the empirical evidence for heterozygote advantage in other common genetic diseases is quite weak. I introduce and illustrate the significance of a hierarchy of genetic disease phenomena found within the genetic disease explanations, which include the phenomena: single mutation variants of a common genetic disease, single genetic diseases, and classes of diseases with related phenotypic effects. I demonstrate that some of the confusion over the explanations of common genetic diseases can be traced back to confusions over which phenomena are being explained. I proceed to briefly evaluate the existing evidence for two common human genetic diseases: Tay Sachs disease and cystic fibrosis. The above considerations will ultimately shed light on why these diseases’ evolutionary explanations remain so deeply unresolved after so such a great volume of research. (shrink)

In Victoria, Australia, some parents are now able to select embryos free from genetic disease which will provide stem cells to treat an existing siblingA n Australian couple from Victoria have been given permission to use in vitro fertilisation technology to screen an embryo in order to “create a `perfect match’ sibling” for their seriously ill child. In vitro fertilisation is regulated in Victoria by the Infertility Treatment Authority which restricts access to people who are medically infertile or who have (...) a family history of genetic disease. The approval given to the Victorian couple is for a new application of IVF consisting of preimplantation genetic diagnosis together with tissue typing.The couple’s three year old daughter Christina has Fanconi’s anaemia, a rare genetic condition, that means she will die before she turns 15 unless she receives blood from the umbilical cord of a “perfect match” sibling. Some people are saying this use of IVF amounts to the creation of a genetically engineered “designer” baby. 1–6Preimplantation genetic diagnosis is an IVF technique …. (shrink)

Race is a prominent category in medicine. Epidemiologists describe how rates of morbidity and mortality vary with race, and doctors consider the race of their patients when deciding whether to test them for sickle‐cell anemia or what drug to use to treat their hypertension. At the same time, critics of racial classification say that race is not real but only an illusion or that race is scientifically meaningless. In this paper, I explain how race is used in medicine as (...) a proxy for genes that encode drug metabolizing enzymes and how a proper understanding of race calls into doubt the practice of treating race as a marker of any medically relevant genetic trait. (shrink)

Gene therapy and gene editing are revolutionising the treatment of genetic diseases, most notably haematological disorders. This paper evaluates the use of both techniques in hereditary blood disorders. Many studies have been conducted in this field, especially with gene therapy, with very promising results in diseases such as haemophilia, certain haemoglobinopathies and Fanconi anaemia. The application of these techniques in clinical practice and the foreseeable development of these approaches in the coming years suggest that it might be useful to evaluate (...) the results achieved thus far. It is also essential to reflect on the possible bioethical concerns raised by the use of both techniques, especially in terms of safety issues for patients, potential side effects, treatment duration, accessibility and cost of treatment, and the heritability of genetic changes produced if germline cells are used. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Fetal Tissue ResearchMary Carrington Coutts (bio)I. IntroductionThe use of tissue from fetal remains for transplantation and biomedical research has become a controversial issue in recent years, involving scientists, doctors, patients, and the federal government. Fetal tissue is potentially useful in a wide range of treatments for a number of serious diseases, some of them affecting millions of people. Despite the promise, transplantation research using fetal tissue from induced abortion (...) slowed dramatically in the U.S. in 1988, when a moratorium was declared on federal funding for such research involving humans. That moratorium was lifted by President Clinton on January 21, 1993. Though the future of fetal tissue transplantation research is brighter, public debate on the issue is likely to continue, exacerbated by the "acrimonious abortion debate" (VI, Post 1991, p. 14).Using fetal tissue in biomedical research and in transplantation is not a new practice. As early as 1928 unsuccessful attempts were made to transplant fetal pancreas cells into diabetics (VII, Fichera 1928). Fetal tissue was used effectively in biomedical research during the 1950s, and was instrumental in the culture of the polio virus, which led to the development of the polio vaccine. Fetal tissue cultures were also essential in the development of the rubella vaccine, and continue to be used in virology research. Transplantation of fetal thymus cells into patients with DiGeorge Syndrome has been recognized as effective therapy since the late 1960s.Many of the therapeutic applications involving fetal tissue are still experimental, so it is difficult to pinpoint fetal tissue transplantation's therapeutic potential. One promising application is the transplantation of human fetal brain cells into the substantia nigra of patients with Parkinson's disease to restore motor function. Fetal neural transplants have also shown promise for patients suffering from Alzheimer's disease, spinal cord and other neural tissue injuries, and possibly some forms of cortical blindness. Fetal liver cells may be useful for treatment of some kinds of bone marrow disease seen in leukemia and aplastic anemia patients. [End Page 81] Fetal tissue transplantation may also help those suffering from blood clotting disorders, such as sickle cell anemia, thalassemia, and hemophilia. Fetal pancreatic tissue has potential applications in the treatment of diabetes, especially juvenile onset diabetes. Human gene therapy may also employ embryonic and early fetal cells.The Center for Biomedical Ethics at the University of Minnesota reports that more than 1,000 patients have received transplanted fetal tissue worldwide. Countries where fetal tissue transplantation has occurred include: Australia, Canada, China, the Commonwealth of Independent States (formerly the U.S.S.R.), Cuba, Czechoslovakia, Finland, France, Germany, Great Britain, Hungary, India, Italy, Mexico, Norway, Spain, Sweden, and Yugoslavia (IV, Vawter 1992, p. 2; I, Spain 1988; VII, Reinikainen 1989).Fetal tissue has unique characteristics that make it especially valuable in some treatments. Fetal cells develop much faster than adult cells, hastening the therapeutic effect—a potentially significant benefit for gravely ill patients. They are also less likely to be rejected by transplant recipients because they are less antigenic than adult cells. This reduces the need for the exact tissue matches that can be so difficult to obtain. Fetal tissue is also easier to culture and proliferates more readily than comparable adult tissue. Furthermore, fetal tissue is in greater supply, due to the number of elective abortions.Questions about the use of fetuses and fetal tissue in biomedical research were raised in the United States in the early 1970s. Between 1969 and 1973, all 50 states enacted the Uniform Anatomical Gift Act, allowing for the donation of all or part of the body of a dead fetus for research or therapeutic research. Prospects for the use of fetal tissue increased after the Supreme Court decision in Roe v. Wade legalized abortion. As the availability of fetal tissue increased so did the concern over the potential for controversial research on living, soon-to-be-aborted fetuses, and anxiety over maltreatment of dead abortuses. Vivid examples include Geoffrey Chamberlain's 1968 report of an experiment on a fetus of 26 weeks gestational age. Delivered by hysterotomy from a 14-year-old patient, the fetus was attached to an "artificial placenta" and kept alive for more than... (shrink)

The article deals with sport as a factor of creativity. The theses have been developed as follows. 1. Management of sport is an extreme case, on the base of which we can proof creativity of management and managers. 2. We face the contradiction of cultures not because of their difference but because of their uniformity and anaemia, i. e. morbidity when colourful details conflict after their contents assimilate. 3. A good piece of work threatens to overstep the limits of the (...) rational (cultural) region and to stay not understandable; these characteristics follow from its ungovernable nature and are the components of a good piece of art. 4. As a limit of culture, nature allows for a creator loosing a touch with his (her) creative whole that is to be overstepped constantly; sport is appealing to the nature. 5. Adventures, ventures, long distant tours and extreme sport disturb work and distract a creator by threatening not as much with physical dangers as with unrealized ideas; creation is donkeywork by distancing from external disturbs. 6. The body in sport and the creation are inseparable. 7. Being sport fans, we not only simulate creativity but also create our identity, life style and life art; beside this, we touch the creativity nourished in a social way through our identity and social capital. (shrink)

Johanna Knapstein,1 Daniel Grimm,1 Marcus A Wörns,1 Peter R Galle,1 Hauke Lang,2 Tim Zimmermann111st Department of Internal Medicine, Johannes Gutenberg-University, Mainz, Germany; 2Department of General, Visceral and Transplantation Surgery, Johannes Gutenberg-University, Mainz, GermanyIntroduction: Hepatitis C virus reinfection occurs universally after liver transplantation, with accelerated cirrhosis rates of up to 30% within 5 years after liver transplantation. Dual antiviral therapy with pegylated interferon-2a and ribavirin only reaches sustained virological response rates of ~30% after liver transplantation. With the approval of viral NS3/4A (...) protease inhibitors telaprevir, boceprevir, and simeprevir and the NS5B polymerase inhibitor sofosbuvir, combination therapy offers new therapeutic options for HCV-infected patients, resulting in considerably higher sustained virological response rates in the nontransplant setting. Case presentation: We report three cases of TVR-based triple antiviral therapy in HCV genotype 1 reinfected patients after liver transplantation, of whom a 57-year-old Caucasian female and a 43-year-old Caucasian male were therapy naïve, and a 49-year-old Caucasian male patient was pretreated ineffectively. After 4 weeks of therapy, viral load decreased one to three log10 and became negative in weeks 6 to 8 in the therapy naïve patients. The pretreated patient showed a negative viral load in week 4. TVR was administered over 12 weeks, 750 mg thrice daily. Doses of immunosuppression with cyclosporine were reduced four to six fold. Initial peg-IFN and RBV doses ranged from 135–180 µg/week and 800–1,200 mg/day, according to the patient's body weight. Doses of peg-IFN and RBV were adapted to 90–135 µg/week and 400–800 mg/day after 2 to 12 weeks of protease inhibitor therapy. Dual therapy was continued for 36 weeks with total treatment duration of 48 weeks in the therapy naïve patients leading to a sustained virological response 12 weeks after the end of therapy. In the pretreated patient a breakthrough was detected in week 24 and therapy was discontinued. Overall, antiviral therapy was well tolerated. Side effects included dysgeusia and anemia leading to erythropoietin application and blood transfusions. Conclusion: This case series emphasizes that triple therapy with TVR is an efficient treatment for therapy naïve HCV genotype 1 reinfected patients after liver transplantation. But therapeutic options for pretreated patients require improvement. Keyword: cyclosporine, interferon, ribavirin, hepatitis C, protease inhibitor. (shrink)

India is home to 243 million adolescents. Two million of them belong to Scheduled Tribes living in underserved, rural areas. Few studies have examined the health of tribal adolescents. We conducted a cross-sectional survey to assess the health, nutrition and wellbeing of adolescent girls in rural Jharkhand, eastern India, a state where 26% of the population is from Scheduled Tribes. We aimed to identify priorities for community interventions to serve adolescents and their families. Between June 2016 and January 2017, interviewers (...) visited all households in 50 purposively sampled villages of West Singhbhum district, Jharkhand. They aimed to interview all girls aged 10–19. Interviewers conducted face-to-face interviews with girls to administer a survey about physical and mental health, disability, nutrition, sexual and reproductive health, gender norms, decision-making, education and violence. Interviewers also measured girls’ height, weight, and Mid-Upper Arm Circumference. Interviewers collected data from 3324 of an estimated 4068 girls residing in the study area. Their mean age was 14.3. 82% were from Scheduled Tribes. 89% of younger girls aged 10–14 and 46% of older girls aged 15–19 were in school or college. Girls dropped out of school because they were required for household work or work on the family farm or business. Over a third reported symptoms of anaemia in the past month, but less than a fifth had a blood test. The prevalence of thinness was 14% for younger girls and 6% for older girls. 45% of girls were stunted. 40% reported emotional violence in the past year, 14% physical violence, and 0.7% sexual violence. 12% had problems associated with depression or anxiety. 30% aged 15–19 had heard of contraception. Among married girls and their husbands, only 10% had ever used methods to prevent or delay pregnancy. Our study identified several priorities to improve adolescent girls’ health, nutrition and wellbeing in largely tribal areas of Jharkhand: reducing violence, early marriage and undernutrition, as well as improving mental health, knowledge about contraception and school retention. (shrink)

The Office of Inspector General, Department of Health and Human Services, has issued a proposed rule under section 5201 of the Omnibus Consolidated and Emergency Supplemental Appropriations Act for Fiscal Year 1999 that would provide a safe harbor from civil sanctions under section 1128A of the Social Security Act for independent dialysis facilities that pay premiums for Supplementary Medical Insurance or Medicare Supplemental Health Insurance Policies for financially needy Medicare beneficiaries with end-stage renal disease.End-stage renal disease is a chronic disease (...) that requires regular dialysis treatments and monitoring of laboratory values, diet and medication. ESRD patients suffer from irreversible renal failure, often accompanied by diabetes, anemia, hypertension and congestive heart failure. (shrink)

How is a disease contracted, and how does it progress through the body? Answers to these questions are fundamental to understanding both basic biology and medicine. Advances in the biomedical sciences continue to provide more tools to address these fundamental questions and to uncover questions that have not been thought of before. Despite these major advances, we are still facing conceptual and technical challenges when learning about the etiology of disease, especially for genetic diseases. In this review, we illustrate this (...) point by discussing the causal links between molecular mechanisms and systems-level phenotypes in molecular diseases. We begin with an examination of sickle cell anemia, and how mechanisms of the disease have been comprehended over the last century. While sickle cell anemia involves a mutation in a single protein in a single cell type, other diseases involve mutations in networks with many protein interactions and in diverse cell types. We introduce the challenges that result from these differences and illustrate the current obstacles by discussing the RASopathies, a recently discovered class of developmental syndromes that result from mutations in signaling networks. Methods to study mutant genotypes that lead to mutant phenotypes are discussed, particularly the use of model organisms and mutant proteins to study protein interactions that may be important for development of disease. These studies will point toward the future of diagnosing and treating genetic disease. (shrink)

David DeGrazia1 offers, to my mind, a decisive response to the bioconservative suggestion that moral bioenhancement threatens human freedom or undermines its value. In this brief commentary, I take issue with DeGrazia's way of defining MB. A different concept of MB exposes a danger missed by his analysis.Two ways to define MBDeGrazia presents MB as a form of enhancement directed at moral capacities. There are, in the philosophical literature, two broad approaches to defining human enhancement. Simplifying somewhat, one account identifies (...) enhancement with improvement. DeGrazia joins other advocates of MB in preferring this type of account, defining a human enhancement as ‘any deliberate intervention that aims to improve an existing capacity, select for a desired capacity, or create a new capacity in a human being.’1An alternative approach relativises enhancement to human norms.2 ,3 In this view, improvements up to levels of functioning properly considered normal for humans are therapy, not enhancement. Improvements beyond those levels are enhancements. The injection of synthetic erythropoietin by someone suffering from anaemia is therapy. When healthy Tour de France competitors inject EPO, it is enhancement.We can minimise philosophical disputes about word meanings by endorsing a conceptual pluralism that acknowledges the need for more than one concept of human enhancement to address the hugely varied ways in which technology may alter humans. In the debate about biomedical moral improvements there would be enhancement as improvement and enhancement beyond human norms.DeGrazia effectively deploys the concept of enhancement as improvement to …. (shrink)

As the rapidly advancing possibilities of biotechnology have outstripped the adaptive capacity of current legal and ethical institutions, a vigorous debate has arisen that considers the boundaries of appropriate use of this technology, particularly when applied to humans. This article examines ethical concerns surrounding the development of markets in a particular form of human genetic engineering in which heterozygotes are fitter than both homozygotes, a condition known as heterozygous advantage. To begin, we present a generalized model of the condition, illuminated (...) by the application to sickle-cell anemia. Next, we propose a typology of related markets, some of which are currently functioning with available products and services, and others that are widely viewed as imminent. We suggest the manner in which perverse incentives may arise for firms that market genetic intervention in circumstances where heterozygous advantage is possible. Finally, we propose that this misalignment of incentives with social welfare has arisen from both ill-conceived market intervention where markets are capable of achieving efficient outcomes and the lack of market intervention where markets have failed. We offer specific legal and regulatory approaches for reform. (shrink)

SummaryIn 1968, a prospective study was started in collaboration with the Family Planning Association to try to provide a balanced view of the beneficial and harmful effects of different methods of contraception. This investigation is now in progress at seventeen clinics and over 17,000 women are under observation. At the time of recruitment, all these women were married white British subjects, aged 25–39 years, who voluntarily agreed to participate. Fifty-six per cent were using oral contraceptives, 25% were using a diaphragm (...) and 19% were using an intrauterine device. During follow-up each woman is questioned at return visits to the clinic and a record of pregnancies and their outcome, hospital referrals, changes in contraceptive methods and the results of cervical smears, is accumulated. Women who default are sent a postal questionnaire and, if this is not returned, are telephoned or visited in their homes to collect the necessary information.So far, data obtained during 56,000 woman-years of observation are available for analysis. Follow-up has been maintained with an annual lapse rate of about 0.3%due to withdrawal of co-operation or loss of contact; adherence to the method of contraception in use at recruitment has been reasonably good, and the reporting of pregnancies and hospital admissions appears to have been both reliable and unbiased.The present data include only 24 deaths, so the mortality associated with different contraceptive methods cannot yet be estimated. With regard to morbidity, however, our preliminary results closely resemble those obtained in the prospective study carried out by the Royal College of General Practitioners and in the principal retrospective studies carried out in Britain and the United States. Women who used oral contraceptives at the start of the study experienced adeficiencyof hospital referrals for cancer, benign lesions of the breast, menstrual disorders other than amenorrhoea, duodenal ulcer, and retention cysts of the ovary; they showed anexcessof referrals for cerebrovascular disease, cervical erosion, skin disorders, self-poisoning, migraine, venous thrombosis and embolism, hayfever, gallbladder disease, amenorrhoea, and sterility. Women who used a diaphragm showed adeficiencyof hospital referrals for carcinoma-in-situ and dysplastic lesions of the cervix uteri and accidental injury; and anexcessof referrals for haemorrhoids and cystitis. Women who used an IUD experienced anexcessof hospital referrals for anaemia, varicose veins and salpingitis. About half of these differences were predicted from other studies while some suggestive evidence already existed for a further five. Of the remaining six, some probably reflect the influence of selective factors or chance.Multiple pregnancies, stillbirths, malformations, the sex ratio and birthweight showed no consistent relationship to method of contraception. The outcome of unplanned pregnancies occurring in women using an IUD, however, was remarkably unfavourable both in terms of ectopic gestation and miscarriage.Clear evidence was found of impairment of fertility after discontinuation of oral contraceptives. Whether this is likely to lead to permanent sterility in some women is uncertain.The study has provided data on the efficacy of a wide variety of contraceptive methods. In general the failure rates are in keeping with those obtained in other large-scale studies, save that those for the diaphragm and the sheath are much lower than those usually quoted.The available evidence does not yet allow a final balance to be struck between the benefits and risks associated with the new methods of contraception that have become widely used during the last two decades. It seems clear, however, that there are no material risks associated with the use of the diaphragm apart from the risk of pregnancy and that there may be some unintended benefits. (shrink)

Clinical red blood cell transfusion guidelines have been widely adopted in clinical practice, resulting in standardized transfusion practices in hospitalized patients with anemia. Standardization of transfusion practice has been welcomed by clinicians and health systems as a mechanism for reducing unnecessary, harmful, and costly practice variation that results in healthcare disparities. However, overzealously applied guidelines can have deleterious consequences for individual patients, ultimately resulting in and/or exacerbating healthcare disparities, rather than resolving them. This article provides empirical examples of the (...) adverse consequences from the well-meaning attempt to standardize transfusion practice based on clinical practice guidelines and discusses the ethical implications of standardized transfusion practice. (shrink)

Advances in understanding genetic disorders have been rapid in the last few years and with them the need and desire for genetic counselling have grown. Almost simultaneously, particularly in the USA, several large screening programmes have been initiated to screen large numbers of people who may be carriers of such deleterious genes as those of Tay-Sachs disease and sickle cell anaemia. The authors of this paper, clinical medical students at University College Hospital, London, spent some time studying the ethical issues (...) raised. The first part of their study, which is not published here, relates to the biochemistry of certain genetic disorders, so leading up to the aspect of the subject which must concern readers of this journal, genetic counselling. At present genetic counselling is generally the province of the medical practitioner working with clinical biochemists, and in this paper their function is described and how programmes of screening for carriers are designed. Whether the subjects of the screening tests are found to be 'innocent' or 'guilty' psychological problems confront them, and of these the genetic counsellor must be aware. In fact the range of ethical problems raised by such counselling is wide and can only be sketched in this article. (shrink)

BackgroundBeta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent.DiscussionThalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy (...) or accept the high mortality risk of HSCT in the hope of obtaining complete recovery.Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome.SummaryOnly if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients. (shrink)

The interconnection of scientific studies and art represented by Leonardo Da Vinci’s portraiture accentuates his role in documenting and archiving dermatologic conditions. His anatomical dissections, sketches, and paintings, including portraits, were all a means to observe, portray, and understand the nuances of the human body. In two of his most discussed portraits, Ginevra de’ Benci and Elisabetta del Giocondo, the Mona Lisa, Leonardo’s execution of the exterior anatomy is so precise that he may have illustrated manifestations of disease that allow (...) contemporary researchers to theorize diagnoses of dermatologic as well as neurologic, endocrine and vascular conditions. These include hypochromic anemia, muscular disorders, xanthelasma, thyroid disease, lipoma, and frontal fibrosing alopecia. Leonardo’s extraordinary talent in recording his observations of shades and textures of skin and his ability to capture the nuances of subtle variations in the human body have produced a historical record that allows modern dermatology practitioners to make further observations not possible in his time. Here, dermatology and art intersect serving to document and explain the human condition, permanently archived in Leonardo’s masterpieces. (shrink)

Imagine your body is populated by billions of respirocytes capable of delivering 236 times more oxygen than your natural red blood cells. These mechanical, micron sized spheres are appropriately programmed by your physician to meet your personal requirements, be it the treatment of anemia or the enhancement of your physical abilities. Robert Freitas’ vision of such artificial blood cells comprised of nanometer-scale components was published in 1998 in a peer-reviewed medical journal, and was the first medical nanorobot design paper (...) to be published.The fact that this proposal for a future blood substitute was accepted as worthy of publication in a scientific journal, despite the inventor's explicit statement that such a device could not be built at the time, clouds the criteria upon which an informed opinion about the feasibility of such devices could be formed. In that respect, the idea of respirocytes formidably testifies to the current “blurring of fact and fiction” occurring in the field of nanotechnology. (shrink)

Skeletons drawn from archaeological contexts provide a fund of data for assessing disease in general and timing of epidemics in particular in past societies. The bioarchaeological record presents an especially important perspective on timing of some of the world's most catastrophic diseases, such as leprosy, tuberculosis, plague (Black Death), and treponematosis. Application of new developments in paleogenomics and paleogenetics presents new opportunities to document ancient pathogens' DNA (for example, Black Death), track their history, and assess their beginning and end points. (...) Paleopathological documentation of disease terminus is complex, in part owing to circumstances where past communities experienced overlapping epidemics, such as leprosy and plague. For most settings, these syndemics-whereby there is an interaction between two or more epidemic diseases-both exacerbate and enhance the burden of morbidity in a community or region. Fundamental to understanding the severity and duration of epidemics is the consideration of multiple factors that simultaneously influence the severity and duration of the specific infectious diseases in a community or region, including poor oral health, under-nutrition, iron deficiency anemia, and elevated parasite load. In our view, comprehending the beginning, the middle, and the end of epidemics requires understanding the wider context of syndemics, the multiple challenging circumstances that undermine health and community stability, and how biosocial factors differentially affect the immune competence of individuals. This article provides several examples of the application of bioarchaeology and syndemics theory in achieving an understanding of how epidemics end. Pathogens continue to circulate, even after what appears to be the end. In effect, then, there is no “end,” just evolution of opportunistic pathogens and our ability (or not) to mitigate them. (shrink)

Society has historically not taken a benign view of genetic disease. The laws permitting sterilization of the mentally re tarded~ and those proscribing consanguineous marriages are but two examples. Indeed as far back as the 5th-10th centuries, B.C.E., consanguineous unions were outlawed (Leviticus XVIII, 6). Case law has traditionally tended toward the conservative. It is reactive rather than directive, exerting its influence only after an individual or group has sustained injury and brought suit. In contrast, state legislatures have not been (...) inhibited in enacting statutes. Many of their products can be characterized as hasty, unnecessary, ill-conceived, and based on the heart rather than the head. Moreover the lack of expert consultation sought has also been remarkable. One state legislature, for example, has advocated immunization for sickle cell anemia! Many others have enacted laws for the screening of inborn errors of metabolism, e.g., phenylketon uria, but have poorly defined the lines of responsibility to secure compliance. A spate of specific disease-related bills has emerged in the u.S. Congress, each seeking recognition and appropriations. Sickle cell anemia, hemophilia, Cooley's anemia and Tay-Sachs disease have been among the front-runners for support. Finally, in 1975, Congress has begun to examine an omnibus bill concerning all forms of genetic disease. The bill, termed the National Genetic Diseases Act is, however, still far from being enacted. (shrink)

A survey was carried out on 108 Chilean children and a selection of their families. The factors studied were: (1) social, (2) demographic and dietaryto assess the incidence and degree of malnutrition and (4) haematology—to determine the incidence of anaemia.

Race is a prominent category in medicine. Epidemiologists describe how rates of morbidity and mortality vary with race, and doctors consider the race of their patients when deciding whether to test them for sickle cell anemia or what drug to use to treat their hypertension. At the same time, critics of racial classification say that race is not real but only an illusion or that race is scientifically meaningless. In this paper, I explain how race is used in medicine (...) as a proxy for genes that encode drug metabolizing enzymes and how a proper understanding of race calls into doubt the practice of treating race as a marker of any medically relevant genetic trait. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Receiving the Gift of Life: My Kidney Transplant StoryJudith W. RyanAs one of three siblings who all inherited an unfortunate gene from our mother, I was born with polycystic kidney disease (PKD). None of us knew of this, however, until later middle age, and my mother not until she was 76. I was the last sibling diagnosed at the age of 56. My brothers had been diagnosed some years (...) before and jokingly started to look at me as a universal donor. Since I had a 50-50 chance of having PKD and with a mother who was one of eight children with none of her siblings known to have the disease, I had not felt an urgency to be tested. Besides, I had no signs or symptoms. But now there was a reason. I made an appointment for a renal ultrasound and while having the procedure, I tipped the screen so that I could see the results. Although the technician was not happy with this, I was repaid with the view of my kidneys looking full of bubbles. Yes, our family was three for three in the genetic game of roulette.I knew immediately how I was going to navigate this health issue. As an adult nurse practitioner I had a very good understanding of what was to come. I knew my blood type “O” was the most common and would mean the longest wait for a deceased donor transplant, at least five years if I were lucky and only after enduring several years of progressing renal failure. In addition, I had cared for dialysis patients and watched my mother endure with difficulty both peritoneal and hemodialysis prior to her death a year before my diagnosis. Knowing I would not choose dialysis left me hoping for a miracle of a living donor or, more realistically, managing my disease as best I could until I died.The next step was managing PKD symptoms and issues as my kidneys continued to fail. One of the errors in my thinking during this time turned out to be that because I had two brothers who had the same disease and were ahead of me in their disease progression, I could follow their lead. It turned out that we manifested our disease very differently. My younger brother, who was diagnosed first, had to deal with significant pain from persistent cyst ruptures, monthly, biweekly then weekly. This continued even after his transplant until he had his native kidneys removed. The other two of us did not have to deal with cyst ruptures. Additionally, anemia was no problem for my younger brother but was for us older siblings. Significant fatigue and weariness were a problem for both of my brothers but not for me.And so it went, as we compared our blood test results, that the idea of a living donor entered the conversation. I knew this would be a problem for me because how do you ask people to consider being a donor? I had difficulty asking friends for a ride to the airport. This is where the grace and kindness of others and divine intervention enter [End Page 107] our story—word about our medical dilemma spread through the visibility of my younger brother, a minister in New England.Fortunately for me, my much beloved younger brother had dozens of people who wanted to be his donor. About 12 of these potential donors were actually tested before finding a match. One of his unmatched donors became the donor for my older brother (our first family transplant). Two years later, my other brother received his transplant. Three years later, after being told he was not a good match for my brother, this dear man came forward to be a possible donor for me. Hence, I got my transplant from an unused donor from my younger brother’s group. Overall, we had living donors from three different churches located within an hour of each other in New England. I even lucked out and acquired the minister of one of the churches as my donor. All three of us received kidneys over five years from living donors who did not know my older brother... (shrink)

Pre-existing medical conditions and co-infections are common to all human populations, although the natures of the pre-existing conditions and the types of co-infections vary. For these reasons, among others, the arrival of a highly infectious pathogenic agent may differentially affect the disease burden in different sub-populations, as a function of varying combinations of endemic disease, chronic disease, genetic or epigenetic vulnerabilities, compromised immunological status, and socially determined risk exposure. The disease burden may also vary considerably by age cohort and socio-economic (...) status. The social consequences of infection, the medical sequelae, and the paths of recovery from infection may also vary, according to these variables. As a result, different sub-populations may have different experiences of a disease process, including when and how an epidemic comes to an end. This essay suggests that historians' engagement with path-breaking biological and medical anthropological research will allow new approaches to understanding disease processes that will enrich the study of epidemics and their endings. It is organized in three sections. The first discusses some general approaches to and assumptions about epidemics that are used by many historians. The second introduces new perspectives on the study of historical epidemics opened up by the medical anthropological concept of syndemic disease interactions and by an engagement with biological scientific perspectives. It briefly discusses two rural epidemics-one of anemia caused by the syndemic interaction of hookworm and malaria co-infections in early 20th-century British Malaya, and the other of rebound infections caused by the loss of acquired immunity to falciparum malaria in mid-20th-century Liberia-that illustrate, respectively, the utility of the concept of syndemic disease interactions and the centrality of immunological status in understanding epidemic outbreaks in these discrete populations. The third section addresses some of the research considerations involved in moving beyond the single pathogen model of epidemic disease. (shrink)

Dyskeratosis congenita is a rare skin and bone marrow failure syndrome caused by defective telomere maintenance in stem cells. The major X‐linked form of the disease is due to mutations in a nucleolar protein, dyskerin, that is part of small nucleolar ribonucleoprotein particles that are involved in processing ribosomal RNA. It is also found in the telomerase complex, pointing to an unexpected link between these two processes. An autosomal dominant form is due to mutations in the RNA component of telomerase (...) (hTR). Patients with this form of the disease are more severely affected in later generations that carry the mutations, possibly due to the inheritance of shortened telomeres, disguising the inherited nature of the disease in some cases classified as aplastic anemia. Because of the importance of telomerase in tumour formation and aging, study of this disease may provide important clues about these fundamental processes. BioEssays 25:126–133, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In 1949, Linus Pauling and collaborators published in Science a paper provocatively titled: 'Sickle cell anemia, a molecular disease'. What was actually meant by 'molecular disease'? We interpret the concept of molecular disease in the frame of the traditional positions about the nature of diseases: the ontological and the physiological positions. We conclude that the physiological does not give an adequate account of what molecular diseases are. The ontological position, when correctly reinterpreted, leads to an understanding of molecular diseases (...) where the macromolecule is seen as a symptom or as a part of a mechanism leading to the symptoms of the disease. We then show that the concept of molecular disease leads to a particular view of therapy, emphasizing eugenics as a way of eliminating disease. On the individual level, this concept leads to an increased power of diagnosis, and especially predictive diagnosis, but has little therapeutic consequence. Lastly, we examine how this concept of disease unifies two contemporary classifications of diseases, one based on the location of the diseases, the other on the cause of the diseases. (shrink)

Son diversos los motivos que justifican analizar, de forma separada, la depresión y los trastornos de ansiedad en personas mayores con respecto a adultos más jóvenes. Podemos enumerar, entre los más relevantes, los siguientes: (1) sintomatología diferencial que puede dificultar el diagnóstico en la vejez; (2) infradeclaración clínica, consecuencia del efecto negativo de los estereotipos de la edad sobre la población mayor y los profesionales que los tratan; (3) mayor cronificación de los síntomas, debido a un posible diagnóstico tardío; (4) (...) mayor impacto funcional, ya que ambos trastornos se pueden asociar a diversas patologías, como anemia o diabetes (en la depresión) o presión arterial, úlcera o problemas cardiovasculares ( en la ansiedad), produciéndose una interacción recíproca entre la sintomatología psicológica y física que exacerba ambos tipos de problemáticas. (shrink)