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Deficiency Syndrome (deficiency + syndrome)
Kinds of Deficiency Syndrome Selected AbstractsAbsence Epilepsy with Onset before Age Three Years: Could this Be Glut-1 Deficiency Syndrome (De Vivo Syndrome)?EPILEPSIA, Issue 1 2004Lawrence J. Hirsch MD No abstract is available for this article. [source] Psychological distress amongst AIDS-orphaned children in urban South AfricaTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 8 2007Lucie Cluver Background:, South Africa is predicted to have 2.3 million children orphaned by Acquired Immune Deficiency Syndrome (AIDS) by 2020 (Actuarial Society of South Africa, 2005). There is little knowledge about impacts of AIDS-related bereavement on children, to aid planning of services. This study aimed to investigate psychological consequences of AIDS orphanhood in urban township areas of Cape Town, South Africa, compared to control groups of children and adolescents orphaned by other causes, and non-orphans. Method:, One thousand and twenty-five children and adolescents (aged 10,19) were interviewed using socio-demographic questionnaires and standardised scales for assessing depression, anxiety, post-traumatic stress, peer problems, delinquency and conduct problems. Results:, Controlling for socio-demographic factors such as age, gender, formal/informal dwelling and age at orphanhood, children orphaned by AIDS were more likely to report symptoms of depression, peer relationship problems, post-traumatic stress, delinquency and conduct problems than both children orphaned by other causes and non-orphaned children. Anxiety showed no differences. AIDS-orphaned children were more likely to report suicidal ideation. Compared to Western norms, AIDS-orphaned children showed higher levels of internalising problems and delinquency, but lower levels of conduct problems. Conclusions:, Children orphaned by AIDS may be a particularly vulnerable group in terms of emotional and, to a lesser extent, behavioural problems. Intervention programs are necessary to ameliorate the psychological sequelae of losing a parent to AIDS. [source] The role of weight for age and disease stage in poor psychomotor outcome of HIV-infected children in Kilifi, KenyaDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 12 2009AMINA ABUBAKAR PHD Aim, We aimed to investigate the contribution of disease stage and weight for age to the variability in psychomotor outcome observed among children with human immunodeficiency virus (HIV) infection. Method, This cross-sectional study involved 48 Kenyan children (20 females, 28 males) aged 6 to 35 months (mean 19.9mo SD 8.9) exposed prenatally to HIV. Two subgroups of HIV-exposed children were seen: those who were HIV-infected and those who were uninfected. The reference population was composed of 319 children (159 females, 160 males) aged 6,35 months, (mean age = 19 months, SD=8.43) randomly selected from the community. Disease stage varied from stage 1 to stage 3, reflecting progression from primary HIV infection to advanced HIV infection and acquired immune deficiency syndrome. A locally developed and validated measure, the Kilifi Developmental Inventory, was used to assess psychomotor development. Result, Using age-corrected psychomotor scores, a significant main effect of HIV status was observed (F(2,38.01)=7.89, p<0.001). Children in the HIV-infected group had lower mean psychomotor scores than the HIV-exposed children and the reference group. In the HIV-infected group, disease stage was a negative predictor and weight for age a positive predictor of psychomotor outcome. Interpretation, Weight for age and disease stage provide viable, easily measurable benchmarks to specify when frequent developmental monitoring and psychomotor rehabilitation are required. Nutritional intervention and other measures aimed at slowing disease progression may delay the onset and severity of psychomotor impairment in the paediatric HIV population in Africa. [source] Type 2 diabetes mellitus and obesity in sub-Saharan AfricaDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2010Vivian C. Tuei Abstract While communicable diseases such as human immunodeficiency virus/acquired immune deficiency syndrome, malaria, and tuberculosis have continued to pose greater threats to the public health system in sub-Saharan Africa (SSA), it is now apparent that non-communicable diseases such as diabetes mellitus are undoubtedly adding to the multiple burdens the peoples in this region suffer. Type 2 diabetes mellitus (T2DM) is the most common form of diabetes (90,95%), exhibiting an alarming prevalence among peoples of this region. Its main risk factors include obesity, rapid urbanization, physical inactivity, ageing, nutrition transitions, and socioeconomic changes. Patients in sub-Saharan Africa also show manifestations of ,-cell dysfunction and insulin resistance. However, because of strained economic resources and a poor health care system, most of the patients are diagnosed only after they have overt symptoms and complications. Microvascular complications are the most prevalent, but metabolic disorders and acute infections cause significant mortality. The high cost of treatment of T2DM and its comorbidities, the increasing prevalence of its risk factors, and the gaps in health care system necessitate that solutions be planned and implemented urgently. Aggressive actions and positive responses from well-informed governments appear to be needed for the conducive interplay of all forces required to curb the threat of T2DM in sub-Saharan Africa. Despite the varied ethnic and transitional factors and the limited population data on T2DM in sub-Saharan Africa, this review provides an extensive discussion of the literature on the epidemiology, risk factors, pathogenesis, complications, treatment, and care challenges of T2DM in this region. Copyright © 2010 John Wiley & Sons, Ltd. [source] Incorrect and incomplete coding and classification of diabetes: a systematic reviewDIABETIC MEDICINE, Issue 5 2010M. A. Stone Diabet. Med. 27, 491,497 (2010) Abstract Aims, To conduct a systematic review to identify types and implications of incorrect or incomplete coding or classification within diabetes or between diabetes and other conditions; also to determine the availability of evidence regarding frequency of occurrence. Methods, Medical Subject Headings (MeSH) and free-text terms were used to search relevant electronic databases for papers published to the end of August 2008. Two researchers independently reviewed titles and abstracts and, subsequently, the full text of potential papers. Reference lists of selected papers were also reviewed and authors consulted. Three reviewers independently extracted data. Results, Seventeen eligible studies were identified, including five concerned with distinguishing between Type 1 and Type 2 diabetes. Evidence was also identified regarding: the distinction between diabetes and no-diabetes, failure to specify type of diabetes, and diagnostic errors or difficulties involving maturity-onset diabetes of the young, latent autoimmune diabetes in adults, pancreatic diabetes, persistence of foetal haemoglobin and acquired immune deficiency syndrome (AIDS). The sample was too heterogeneous to derive accurate information about frequency, but our findings suggested that misclassification occurs most commonly in young people. Implications relating to treatment options and risk management were highlighted, in addition to psychological and financial implications and the potential impact on the validity of quality of care evaluations and research. Conclusions, This review draws attention to the occurrence and implications of incorrect or incomplete coding or classification of diabetes, particularly in young people. A pragmatic and clinically relevant approach to classification is needed to assist those involved in making decisions about types of diabetes. [source] Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in IndonesiaADDICTION, Issue 6 2010Rudi Wisaksana ABSTRACT Background There is a common belief that injecting drug use (IDU) is associated with lower uptake, retention and success of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected patients. We examined this in an Indonesian setting, where IDU is the main risk factor for HIV infection. Methods Patient characteristics and response to ART were recorded for all patients diagnosed with HIV infection in the referral hospital for West Java (40 million people). Kaplan,Meier estimates and Cox's regression were used to compare mortality, loss to follow-up and virological failure between patients with and without a history of IDU. Result A total of 773 adult HIV patients (81.9% IDUs) presented between January 1996 and April 2008. IDUs had a median CD4 cell count of 33 [interquartile ratio (IQR), 12,111] cells/mm3 compared to 84 (IQR, 28,224) cells/mm3 in non-IDUs. Among patients with a history of IDU, 87.7% were coinfected with hepatitis C (HCV). Mortality was associated strongly with CD4 count; after 6 months of ART, 18.3, 20.3, 7.1 and 0.7% of patients with CD4 cell counts <25, 25,99, 100,199, respectively, ,200/mm3 had died (P < 0.0001). Mortality [adjusted for CD4; hazard ratio (HR) = 0.65; 95% confidence interval (CI) 0.35,1.23], loss to follow-up (HR = 0.85, 95% CI 0.51,1.41) and virological failure (HR = 0.47, 95% CI 0.19,1.13) were not significantly different in IDUs and non-IDUs. Conclusion Intravenous drug users (IDUs) in Indonesia with HIV/acquired immune deficiency syndrome tend to have more advanced disease but respond similarly to non-IDUs to antiretroviral therapy. [source] Symptomatic Epilepsies Imitating Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Hirokazu Oguni Summary:, The diagnosis of idiopathic generalized epilepsies (IGEs) is not generally difficult if one follows the clinical and electroencephalogram (EEG) definitions of each subsyndrome that constitutes IGEs. In contrast, symptomatic epilepsies develop based on organic brain lesions and are easily diagnosed by the presence of developmental delay, neurologic abnormalities, and a characteristic seizure and EEG pattern. However, in clinical practice, it is sometimes difficult to differentiate IGEs from symptomatic epilepsies, especially when the clinical course from the onset of epilepsy is too short to exhibit typical clinical and EEG findings of either epilepsy type, or when patients with symptomatic epilepsies have atypical features that imitate the clinical characteristics of IGEs. The neurodegenerative or metabolic disorders at times start during the clinical course with epileptic seizures and later show typical neurologic abnormalities. The newly recognized metabolic disorder of glucose transporter type 1 deficiency syndrome (Glut-1 DS) may start with myoclonic seizures at an age of less than 1 year and imitate benign myoclonic epilepsy in infancy early in the clinical course. Progressive myoclonus epilepsies (PMEs) that develop at 1,4 years of age at times imitate epilepsy with myoclonic-astatic seizures with respect to the presence of astatic seizures and an epileptic encephalopathic EEG pattern. In addition, young children with focal cortical dysplasia may also have similar clinical and EEG patterns, although the latter may become localized after treatment. Approximately 15% of patients with juvenile myoclonic epilepsy (JME) are resistant to antiepileptic drugs (AEDs) and may require extensive study to make a differential diagnosis from symptomatic epilepsies. PMEs that develop during adolescence may imitate JME early in the clinical course; however, a detailed history and the differentiation between myoclonic seizures and myoclonus would help to distinguish both conditions. The diagnosis of IGEs is very demanding for patients with atypical features with regard to seizure type, EEG findings, and response to appropriate AEDs. [source] Relationship between knowledge and attitudes regarding HIV/AIDS among dental school employees and studentsEUROPEAN JOURNAL OF DENTAL EDUCATION, Issue 3 2004K. M. Börsum Objectives:, Employees and students at the Faculty of Dentistry, University of Oslo responded to a comprehensive questionnaire regarding knowledge and attitudes towards human immunodeficiency virus (HIV). The intention of the present study was to describe possible relationships between the two. Method:, The questionnaire consisted of 39 closed questions. The response rate was 75% (436/584). The answers were used to construct additive indices for knowledge and attitudes. Results:, The knowledge index reflected the number of correct answers concerning risk groups and transmission. A factor analysis revealed three dimensions of attitudes (,legal', ,personal risk', and ,personal consequences'), which were analysed separately against knowledge. Correlation analyses (Spearman r) of all respondents together (n = 436) revealed a weak, but statistically significant, positive correlation between knowledge and the ,legal' and ,personal risk' dimension of attitudes (r = 0.16, P < 0.01; r = 0.21, P < 0.001). The ,personal consequence' dimension was not significantly correlated with knowledge (r = 0.06, P > 0.05). The strongest correlation was found between knowledge and the ,legal' dimension (r = 0.43, P < 0.001), and knowledge and the ,personal risk' dimension (r = 0.41, P < 0.002) amongst fourth year students. No particular group of employees or students displayed a significant correlation between knowledge and the ,personal consequence' dimension of attitudes. Conclusions:, Three dimensions on attitudes concerning patients with HIV/acquired immune deficiency syndrome were identified amongst the respondents. A weak correlation between knowledge and two of the attitudes might indicate that knowledge plays a role in this respect. [source] To switch or not to switch , the opposing roles of TACI in terminal B cell differentiationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2007Ulrich Salzer MD Abstract The TNF superfamily ligands BAFF and APRIL and their three receptors BAFFR, BCMA, and TACI comprise a network that is critically involved in the development and function of humoral immunity. Failure of this complex system is associated with autoimmune disease, B lymphocyte tumours, and antibody deficiency. While BAFF:BAFFR interactions control peripheral B cell survival and homeostasis, BCMA function seems limited to the survival of long-lived bone marrow plasma cells. The functional activity of the third receptor TACI is, however, ambiguous: while TACI,/, mice predominantly develop autoimmunity and lymphoproliferation, TACI deficiency in humans primarily manifests itself as an antibody deficiency syndrome. An article in this issue of the European Journal of Immunology demonstrates a negative regulation via TACI in human B cells by using TACI specific antibodies. B cell proliferation, class switch recombination, and Ig production induced by various stimuli were inhibited via TACI. Within the BAFF/APRIL network, the expression of the receptors and ligands is spatially, as well as temporally, highly regulated at various stages of B cell development and function. Defining the exact contribution of TACI stimulation by specific triggers in vitro enables us to better understand the complex, context-dependent responses initiated by TACI in vivo. See accompanying article http://dx.doi.org/10.1002/eji.200636623 [source] Evaluation of coexistence of the Human Herpesvirus type 8 (HHV-8) infection and pemphigusINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2010Naser Tayyebi Meibodi Associate Professor Background, Human Herpesvirus type 8 (HHV-8) is a new member of the herpes virus family, first found in the tissue of acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma. Environmental factors including viral infection may play a role in the onset and/or development of pemphigus. Some studies based on polymerase chain reaction findings suggest an association between HHV-8 and pemphigus. The aim of this study is investigation of the association of pemphigus with HHV-8 and the relationship between inflammatory and acantholytic cells with HHV-8 infection. Methods, Tissue-extracted DNA from 41 paraffin-embedded skin tissues from patients first presenting with pemphigus was tested using nested PCR for the presence of HHV-8. A total of 37 cases had pemphigus vulgaris (PV) and 4 patients had pemphigus foliaceus (PF). For our control group, normal skin of 21 cosmetic surgery patients were included. Furthermore, microscopic slides with H&E staining were evaluated for the number of inflammatory and acantholytic cells per microscopic field. Results, Skin lesions from 13 of 37 patients (35.1%) with PV and 2 of 4 cases (50%) with PF were positive for HHV-8 DNA. All specimens in our control group were negative for this virus. Conclusion, HHV-8 infection might be a contributing factor in the initiation or development of pemphigus. [source] Recent trends in the treatment of testosterone deficiency syndromeINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2007Bum Sik Hong Abstract: Testosterone deficiency syndrome (TDS) is defined as a clinical and biochemical syndrome associated with advancing age and is characterized by typical symptoms and deficiency in serum testosterone levels. TDS is a result of the interaction of hypothalamo-pituitary and testicular factors. Now, treatment of TDS with testosterone is still controversial due to a lack of large, controlled clinical trials on efficacy. The risks of treatment with testosterone appear to be minimal, although long-term studies on the safety of testosterone therapy are lacking. The aim of the therapy is to establish a physiological concentration of serum testosterone in order to correct the androgen deficiency, relieve its symptoms and prevent long-term sequelae. All of the available products, despite their varying pharmacodynamic and pharmacokinetic profiles, are able to reach this goal. Newer testosterone patches seem not to cause severe skin irritation. Testosterone gels minimize the skin irritation while providing flexibility in dosing and a low discontinuation rate. Oral testosterone undecanoate (TU) is free of liver toxicity. Recent formulation of oral TU markedly increased shelf-live, a major drawback in the older preparation. Producing swings in testosterone levels rising rapidly to the supraphysiological range is not the case with the new injectable long-acting preparation of TU. To be able to rapidly react and stop treatment in cases where side-effects and contraindications are detected, the short-acting transdermal and oral delivery modes have certain advantages. However, there is no evidence that the use of an injectable long-acting TU in men with TDS has limitations in clinical application for this reason. The use of dehydroepiandrosterone is still controversial because of a lack of well designed long-term trials, although some recent studies suggest positive effects on various body systems. Only a few studies have been carried out to investigate the effect of hCG (human chorionic gonadotropin) in TDS with some positive results on various body systems. [source] Older Women and HIV: How Much Do They Know and Where Are They Getting Their Information?JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 9 2004Susan J. Henderson MD Objectives: To assess older urban women's knowledge about sexual transmission of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and to evaluate the relationship between their HIV/AIDS knowledge level and sources of information. Design: Cross-sectional survey conducted between June 2001 and July 2002. Trained research assistants administered a questionnaire in a face-to-face interview. Setting: General medicine clinic in a large public hospital in a high HIV/AIDS incidence area. Participants: Five hundred fourteen women aged 50 and older. Measurements: Nine questions assessing knowledge of risk of HIV sexual transmission with potential scores ranging from 0 to 9 correct answers. Participants identified all sources of HIV information. Results: The mean knowledge score was 3.7 out of a possible 9 correct responses (range 0 (3%) to 8 (1%)). Younger age, employment, and higher educational level were associated with higher knowledge scores, whereas marital status was unrelated. No respondent correctly answered all of the nine questions. The most commonly identified sources of HIV/AIDS information were television (85%), friends (54%), and newspapers (51%). Only 38% of respondents identified health professionals as a source of information about HIV/AIDS. Health professionals, newspapers, and family members were each independently associated with higher knowledge scores (P<.05). Conclusion: Older women in a general medicine clinic had limited knowledge of sexual transmission of HIV. HIV/AIDS education specifically targeted to this subpopulation is warranted, and health professionals may have an important role in disseminating such messages. [source] Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's sarcoma: Bidirectional translational scienceJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006Bruce J. Dezube Through the mentorship process, Dr. Arthur Pardee emphasized the critical importance of bidirectional translational research,not only advancing drug development from bench to bedside, but also bringing back precious clinical material to the laboratory to assess the biologic effects of therapeutic agents on their targets. This mini-review focuses on the signal transduction pathways of Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the rational development of molecularly targeted pathogenesis-driven therapies. Acquired immune deficiency syndrome (AIDS) related-KS results from co-infection with human immunodeficiency virus and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8), which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of KS. KS is driven by KSHV/HHV8-specific pathways, which include viral G protein-coupled receptor (vGPCR), viral interleukin-6 (vIL-6), and viral chemokine homologues. In addition, cellular growth/angiogenic pathways, such as vascular endothelial growth factor (VEGF), insulin-like growth factor, platelet-derived growth factor (PDGF), angiopoietin and matrix metalloproteinases (MMPs) are "pirated" by KSHV/HHV8. As a very tangible example of how translational research has led to a marked improvement in patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors were serially biopsied. Not only did the patients' tumors regress, but also the regression was correlated with the inhibition of PDGF receptor (PDGFR) in the biopsy samples. Recent and future clinical trials of molecularly targeted therapy for the treatment of KS are a prelude to a shift in the paradigm of how KS is managed. J. Cell. Physiol. 209: 659,662, 2006. © 2006 Wiley-Liss, Inc. [source] The chemokine system and CCR5 antagonists: potential in HIV treatment and other novel therapiesJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2009H. Dhami PharmD (Student) Summary Since the recognition of human acquired immune deficiency syndrome, numerous classes of pharmacologic therapeutics have been developed to manage the disease. Current therapy includes co-administration of combinations of drugs classified by their mechanism of action as ,transcriptase inhibitors', ,protease inhibitors', ,integrase inhibitors' and the more recent ,fusion inhibitors'. This review focuses on the chemokine system and the recognition of chemokine receptors as targets for anti-human immunodeficiency virus (HIV) therapy. The FDA-approved chemokine (C,C motif) receptor 5 (CCR5) antagonist maraviroc (Selzentry®) is discussed in detail, along with another compound vicriviroc, currently in clinical trials. The mechanism of action, pharmacokinetics, toxicity and current status of research on CCR5 antagonists is described. Further, potential therapeutic uses of these agents other than anti-HIV therapy are discussed. [source] Medicines information and adherence in HIV/AIDS patientsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2006L. E. Mansoor BPharm Summary Background:, Providing written medicines information is being legislated in an increasing number of countries worldwide, with the patient information leaflet (PIL) being the most widely used method for conveying health information. The impact of providing such information on adherence to therapy is reportedly unpredictable. Therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and related opportunistic infections usually involves polytherapy and complex regimens, both of which are risk factors for non-adherence. The objective of this study was to assess the impact of medicines information on adherence to chronic co-trimoxazole therapy in low-literate HIV/AIDS patients. Methods:, Two different PILs were designed for co-trimoxazole tablets and were available in both English and isiXhosa. Participants were randomly allocated to a control group (receiving no PIL), group A (receiving a ,complex PIL') and group B (receiving a ,simple PIL' incorporating pictograms). At the first interview, demographic data were collected and the time, date and day that the participant would take his/her first tablet of the month's course was also documented. In a follow-up interview adherence to therapy was assessed using two methods; self-report and tablet count. Results:, The medicines information materials incorporating simple text and pictograms resulted in significantly improved adherence to therapy in the short term, whereas a non-significant increase in adherence was associated with the availability of the more complex information. This was shown by both the self-reported assessment as well as the tablet count. Conclusion:, This research suggests that appropriately designed written material can have a positive impact in improving adherence and, together with verbal consultation, are essential for enabling patients to make appropriate decisions about their medicine taking. [source] Eccentric target sign in cerebral toxoplasmosis: Neuropathological correlate to the imaging feature,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2010G.G. Sharath Kumar MD Abstract Cerebral toxoplasmosis remains one of the most common focal brain lesions in patients with acquired immune deficiency syndrome (AIDS). Diagnosis is a challenge because on cranial imaging it closely mimics central nervous system lymphoma, primary and metastatic central nervous system (CNS) tumors, or other intracranial infections like tuberculoma or abscesses. A magnetic resonance imaging (MRI) feature on postcontrast T1-weighted sequences considered pathognomonic of toxoplasmosis is the "eccentric target sign." The pathological correlate of this imaging sign has been speculative. Herein we correlate the underlying histopathology to the MR feature of eccentric target sign in a patient with autopsy-proven HIV/AIDS-related cerebral toxoplasmosis. The central enhancing core of the target seen on MRI was produced by a leash of inflamed vessels extending down the length of the sulcus that was surrounded by concentric zones of necrosis and a wall composed of histiocytes and proliferating blood vessels, with impaired permeability producing the peripheral enhancing rim. J. Magn. Reson. Imaging 2010;31:1469,1472. © 2010 Wiley-Liss, Inc. [source] Seizures, ataxia, developmental delay and the general paediatrician: Glucose transporter 1 deficiency syndromeJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 5 2006David J Coman Aim Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an important condition for the general paediatrician's differential armamentarium. We describe a case series of eight patients in order to raise awareness of this treatable neurometabolic condition. The diagnosis of GLUT1-DS is suggested by a decreased absolute cerebrospinal fluid (CSF) glucose value (<2.2 mmol/L) or lowered CSF: plasma glucose ratio (<0.4). Methods This is a review of eight Queensland patients with GLUT1-DS. The clinical presentation, clinical course, laboratory investigations and treatment outcomes are discussed. Results The clinical features noted in our patient cohort include combinations of ataxia, developmental delay and a severe seizure disorder that is refractory to anticonvulsant medications. Seizures are the most common clinical manifestation and may be exacerbated by phenobarbitone. The paired CSF: plasma glucose results ranged from 0.2 to 0.39 (normal <0.6) with an average of 0.33. 3-O-Methyl-D-Glucose uptake and GLUT1 Genotyping analysis have been performed on five patients thus far. Rapid and impressive seizure control was observed in 100% of our patients once the ketogenic diet was instituted, with half of the cohort being able to wean completely from anticonvulsants. Conclusion Children presenting with a clinical phenotype consisting of a refractory seizure disorder, ataxia and developmental delay should prompt the consideration of Glucose transporter 1 deficiency syndrome. While the diagnostic test of lumbar puncture is an invasive manoeuvre, the diagnosis provides a viable treatment option, the ketogenic diet. GLUT1-DS displays clinical heterogeneity, but the value of early diagnosis and treatment is demonstrated by our patient cohort. [source] Inference for two-stage adaptive treatment strategies using mixture distributionsJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 1 2010Abdus S. Wahed Summary., Treatment of complex diseases such as cancer, leukaemia, acquired immune deficiency syndrome and depression usually follows complex treatment regimes consisting of time varying multiple courses of the same or different treatments. The goal is to achieve the largest overall benefit defined by a common end point such as survival. Adaptive treatment strategy refers to a sequence of treatments that are applied at different stages of therapy based on the individual's history of covariates and intermediate responses to the earlier treatments. However, in many cases treatment assignment depends only on intermediate response and prior treatments. Clinical trials are often designed to compare two or more adaptive treatment strategies. A common approach that is used in these trials is sequential randomization. Patients are randomized on entry into available first-stage treatments and then on the basis of the response to the initial treatments are randomized to second-stage treatments, and so on. The analysis often ignores this feature of randomization and frequently conducts separate analysis for each stage. Recent literature suggested several semiparametric and Bayesian methods for inference related to adaptive treatment strategies from sequentially randomized trials. We develop a parametric approach using mixture distributions to model the survival times under different adaptive treatment strategies. We show that the estimators proposed are asymptotically unbiased and can be easily implemented by using existing routines in statistical software packages. [source] A hierarchical modelling approach to analysing longitudinal data with drop-out and non-compliance, with application to an equivalence trial in paediatric acquired immune deficiency syndromeJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 1 2002Joseph W Hogan Longitudinal clinical trials with long follow-up periods almost invariably suffer from a loss to follow-up and non-compliance with the assigned therapy. An example is protocol 128 of the AIDS Clinical Trials Group, a 5-year equivalency trial comparing reduced dose zidovudine with the standard dose for treatment of paediatric acquired immune deficiency syndrome patients. This study compared responses to treatment by using both clinical and cognitive outcomes. The cognitive outcomes are of particular interest because the effects of human immunodeficiency virus infection of the central nervous system can be more acute in children than in adults. We formulate and apply a Bayesian hierarchical model to estimate both the intent-to-treat effect and the average causal effect of reducing the prescribed dose of zidovudine by 50%. The intent-to-treat effect quantifies the causal effect of assigning the lower dose, whereas the average causal effect represents the causal effect of actually taking the lower dose. We adopt a potential outcomes framework where, for each individual, we assume the existence of a different potential outcomes process at each level of time spent on treatment. The joint distribution of the potential outcomes and the time spent on assigned treatment is formulated using a hierarchical model: the potential outcomes distribution is given at the first level, and dependence between the outcomes and time on treatment is specified at the second level by linking the time on treatment to subject-specific effects that characterize the potential outcomes processes. Several distributional and structural assumptions are used to identify the model from observed data, and these are described in detail. A detailed analysis of AIDS Clinical Trials Group protocol 128 is given; inference about both the intent-to-treat effect and average causal effect indicate a high probability of dose equivalence with respect to cognitive functioning. [source] Is There a Genetic Basis for Health Disparities in Human Immunodeficiency Virus Disease?MOUNT SINAI JOURNAL OF MEDICINE: A JOURNAL OF PERSONALIZED AND TRANSLATIONAL MEDICINE, Issue 2 2010Cheryl Winkler PhD Abstract The highest global prevalence rates for human immunodeficiency virus and acquired immune deficiency syndrome have been recorded in southern Africa; in the United States, individuals of African descent are disproportionately affected by human immunodeficiency virus infection. Human immunodeficiency virus,infected individuals with African ancestry are also estimated to have a 17-fold or greater risk for developing human immunodeficiency virus,associated nephropathy in comparison with their counterparts of non-African descent. Several recent studies have implicated genetic alleles that are more frequent in populations of African descent and increase the risk of human immunodeficiency virus infection and the risk of human immunodeficiency virus,associated neuropathy (HIVAN). The supposition that persons of African descent are more susceptible to human immunodeficiency virus infection because of an underlying genetic predisposition is not supported by available evidence. However, strong, replicated data show that the increased risk for human immunodeficiency virus,associated nephropathy, as well as other major forms of kidney disease in individuals of African descent, is due in part to MYH9 (myosin, heavy chain 9, non-muscle) renal disease susceptibility alleles that are very frequent throughout sub-Saharan Africa but are infrequent or absent in non-Africans. Selection, drift, and demographic events shape the allelic architecture of the human genome: it is expected that these events will be reflected in geographic-specific differentiation in allele frequencies for a small subset of alleles that may be associated with either increased or reduced risk for complex and infectious diseases. Mt Sinai J Med 77:149,159, 2010. © 2010 Mount Sinai School of Medicine [source] HIV encephalitis simulating Huntington's diseaseMOVEMENT DISORDERS, Issue 5 2005Jeffrey J. Sevigny MD Abstract Complications from human immunodeficiency virus (HIV)/acquired immune deficiency syndrome are notorious for mimicking other neurological diseases. We describe a case of HIV encephalitis presenting with the classic clinical features of Huntington's Disease in a woman without known HIV risk factors or other clinical stigmata suggestive of immunosuppression. This case reminds us that HIV should be part of the differential diagnosis in unexplainable neurological diseases. © 2004 Movement Disorder Society [source] Factors determining prenatal HIV testing for prevention of mother to child transmission in Dar Es Salaam, TanzaniaPEDIATRICS INTERNATIONAL, Issue 2 2007MAYUMI KOMINAMI Abstract Background: The objectives of the study were (i) to evaluate the Prevention of Mother to Child Transmission (PMTCT) services in Temeke district, Tanzania and (ii) to identify factors for non-acceptance of HIV testing among pregnant mothers in the area. Methods: A structured questionnaire was used in face-to-face interviews at five health centers in the district. Univariate and multiple logistic regression analyses were used to assess the association of the refusal of human immunodeficiency virus (HIV) testing with risk factors. Results: Two hundred and seventy-three (68.1%) of the participants had already had HIV testing, while 128 (31.9%) had not. Participants' general knowledge of HIV was high, but specific knowledge of mother to child transmission (MTCT) was relatively low. In the multiple logistic regression analysis, frequencies of antenatal clinic visits, awareness of MTCT and intensive family support were significantly and inversely associated with the refusal of HIV testing. Conclusions: Frequency of antenatal care visits, spreading information on HIV/acquired immune deficiency syndrome especially MTCT, and husbands' intensive support are significant factors for increase of HIV test acceptance among pregnant women in the study area. [source] Expression, purification, and activities of full-length and truncated versions of the integral membrane protein Vpu from HIV-1PROTEIN SCIENCE, Issue 3 2002Che Ma HIV-1, human immunodeficiency virus type 1; AIDS, acquired immune deficiency syndrome; NMR, nuclear magnetic resonance; CNBr, cyanogen bromide; DHPC, dihexanoyl phosphatidylcholine; TROSY, transverse relaxation-optimized spectroscopy Abstract Vpu is an 81-residue accessory protein of HIV-1. Because it is a membrane protein, it presents substantial technical challenges for the characterization of its structure and function, which are of considerable interest because the protein enhances the release of new virus particles from cells infected with HIV-1 and induces the intracellular degradation of the CD4 receptor protein. The Vpu-mediated enhancement of the virus release rate from HIV-1-infected cells is correlated with the expression of an ion channel activity associated with the transmembrane hydrophobic helical domain. Vpu-induced CD4 degradation and, to a lesser extent, enhancement of particle release are both dependent on the phosphorylation of two highly conserved serine residues in the cytoplasmic domain of Vpu. To define the minimal folding units of Vpu and to identify their activities, we prepared three truncated forms of Vpu and compared their structural and functional properties to those of full-length Vpu (residues 2,81). Vpu2,37 encompasses the N-terminal transmembrane ,-helix; Vpu2,51 spans the N-terminal transmembrane helix and the first cytoplasmic ,-helix; Vpu28,81 includes the entire cytoplasmic domain containing the two C-terminal amphipathic ,-helices without the transmembrane helix. Uniformly isotopically labeled samples of the polypeptides derived from Vpu were prepared by expression of fusion proteins in E. coli and were studied in the model membrane environments of lipid micelles by solution NMR spectroscopy and oriented lipid bilayers by solid-state NMR spectroscopy. The assignment of backbone resonances enabled the secondary structure of the constructs corresponding to the transmembrane and the cytoplasmic domains of Vpu to be defined in micelle samples by solution NMR spectroscopy. Solid-state NMR spectra of the polypeptides in oriented lipid bilayers demonstrated that the topology of the domains is retained in the truncated polypeptides. The biological activities of the constructs of Vpu were evaluated. The ion channel activity is confined to the transmembrane ,-helix. The C-terminal ,-helices modulate or promote the oligomerization of Vpu in the membrane and stabilize the conductive state of the channel, in addition to their involvement in CD4 degradation. [source] Associations of Rural Residence With Timing of HIV Diagnosis and Stage of Disease at Diagnosis, South Carolina 2001-2005THE JOURNAL OF RURAL HEALTH, Issue 2 2010Kristina E. Weis PhD Abstract Context: Rural areas in the southern United States face many challenges, including limited access to health care services and stigma, which may lead to later HIV diagnosis among rural residents. Purpose: To investigate the associations of rural residence with timing of HIV diagnosis and stage of disease at diagnosis. Methods: Timing of HIV diagnosis was categorized as a diagnosis of acquired immune deficiency syndrome within 1 year of a first positive HIV test or HIV-only. Stage of disease was based on initial CD4+ T-cell count taken within 1 year of diagnosis. County of residence at HIV diagnosis was classified as urban if the population of the largest city was at least 25,000; it was classified as rural otherwise. Logistic regression was used to analyze timing of HIV diagnosis, and analysis of covariance was used to analyze stage of disease. Findings: From 2001 to 2005, 4,137 individuals were diagnosed with HIV infection. Of these, 1,129 (27%) were rural and 3,008 (73%) were urban residents. Among rural residents, 533 (47%) were diagnosed late, compared with 1,258 (42%) urban residents. Rural residents were significantly more likely to be diagnosed late (OR 1.19 [95% CI, 1.02-1.38]). Rural residence was associated with lower initial CD4+ T-cell count in crude analysis (P= .01) but not after adjustment (P > .05). Conclusions: Rural residence is a risk factor for late HIV diagnosis. This may lead to reduced treatment response to antiretroviral medications, increased morbidity and mortality, and greater HIV transmission risks among rural residents. New testing strategies are needed that address challenges to HIV testing and diagnosis specific to rural areas. [source] Common promoter deletion is associated with 3.9-fold differential transcription of ovine CCR5 and reduced proviral level of ovine progressive pneumonia virusANIMAL GENETICS, Issue 5 2009S. N. White Summary Chemokine (C-C motif) Receptor 5 (CCR5) is a chemokine receptor that regulates immune cell recruitment in inflammation and serves as a coreceptor for human immunodeficiency virus (HIV). A human CCR5 coding deletion (termed delta-32) results in strong resistance to HIV infection, and sequence variants in CCR5 regulatory regions have been implicated in delayed progression to acquired immune deficiency syndrome. Both ovine progressive pneumonia virus (OPPV), also known as maedi-visna, and HIV are macrophage-tropic lentiviruses, have similar genomic structures, and cause lifelong persistent host infection, suggesting CCR5 may have a role in regulating OPPV provirus levels. Therefore, the ovine CCR5 genomic sequence was determined, and sequence variants were obtained from the open reading frame and surrounding regulatory sites. One CCR5 variant contained a 4-base deletion within a binding site for octamer transcription factors in the promoter region. A test for differential transcription from each allele in heterozygous animals showed a 3.9-fold transcription difference (P < 0.0001). OPPV proviral levels were also measured in 351 naturally exposed Rambouillet, Polypay and Columbia sheep. Deletion homozygotes showed reduced OPPV proviral levels among these animals (P < 0.01). The association of this CCR5 promoter deletion with OPPV levels will need to be validated in additional populations before the deletion can be recommended for widespread use in marker-assisted selection. However, because of the large impact on transcription and because CCR5 has roles in inflammation, recruitment of effector cells, and cell-mediated immunity, this deletion may play a role in the control of infections of many diverse pathogens of sheep. [source] Acute hyperglycemia produces transient improvement in glucose transporter type 1 deficiencyANNALS OF NEUROLOGY, Issue 1 2010Cigdem I. Akman MD Objective Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized clinically by acquired microcephaly, infantile-onset seizures, psychomotor retardation, choreoathetosis, dystonia, and ataxia. The laboratory signature is hypoglycorrhachia. The 5-hour oral glucose tolerance test (OGTT) was performed to assess cerebral function and systemic carbohydrate homeostasis during acute hyperglycemia, in the knowledge that GLUT1 is constitutively expressed ubiquitously and upregulated in the brain. Methods Thirteen Glut1-DS patients completed a 5-hour OGTT. Six patients had prolonged electroencephalographic (EEG)/video monitoring, 10 patients had plasma glucose and serum insulin measurements, and 5 patients had repeated measures of attention, memory, fine motor coordination, and well-being. All patients had a full neuropsychological battery prior to OGTT. Results The glycemic profile and insulin response during the OGTT were normal. Following the glucose load, transient improvement of clinical seizures and EEG findings were observed, with the most significant improvement beginning within the first 30 minutes and continuing for 180 minutes. Thereafter, clinical seizures returned, and EEG findings worsened. Additionally, transient improvement in attention, fine motor coordination, and reported well-being were observed without any change in memory performance. Interpretation This study documents transient neurological improvement in Glut1-DS patients following acute hyperglycemia, associated with improved fine motor coordination and attention. Also, systemic carbohydrate homeostasis was normal, despite GLUT1 haploinsufficiency, confirming the specific role of GLUT1 as the transporter of metabolic fuel across the blood-brain barrier. The transient improvement in brain function underscores the rate-limiting role of glucose transport and the critical minute-to-minute dependence of cerebral function on fuel availability for energy metabolism. ANN NEUROL 2010;67:31,40 [source] Fibronectin-binding proteins secreted by Mycobacterium aviumAPMIS, Issue 9 2000HIDEKI Kitaura Mycobacterium avium is an intracellular pathogen and a major opportunistic infectious agent observed in patients with acquired immune deficiency syndrome (AIDS). Fibronectin is an extracellular matrix protein and is a virulence factor for several extracellular pathogenic bacteria binding to mucosal surfaces. We investigated the fibronectin (FN)-binding proteins in the culture filtrate of M. avium by two-dimensional electrophoresis (2DE). Proteins in Sauton medium of M. avium after 3 weeks were separated by 2DE. The proteins were blotted onto polyvinylidene difluoride membrane and incubated with FN. FN-binding proteins were detected by Western blotting using anti-FN antibody. FN bound to five spots (33 kDa, 32 kDa, 31 kDa, 30 kDa and 25 kDa). N-terminal amino acids of these were determined. The 33 kDa spot corresponded to antigen 85 (Ag 85) C. The 32 and 31 kDa spots were either Ag 85 A or Ag 85 B. The 30 kDa spot corresponded to Ag 85 B of M. avium. The 25 kDa spot corresponded to MPA51 (M. avium MPB51). Thus, FN bound exclusively to the Ag 85 complex and MPA51. [source] Joint Inference on HIV Viral Dynamics and Immune Suppression in Presence of Measurement ErrorsBIOMETRICS, Issue 2 2010L. Wu Summary:, In an attempt to provide a tool to assess antiretroviral therapy and to monitor disease progression, this article studies association of human immunodeficiency virus (HIV) viral suppression and immune restoration. The data from a recent acquired immune deficiency syndrome (AIDS) study are used for illustration. We jointly model HIV viral dynamics and time to decrease in CD4/CD8 ratio in the presence of CD4 process with measurement errors, and estimate the model parameters simultaneously via a method based on a Laplace approximation and the commonly used Monte Carlo EM algorithm. The approaches and many of the points presented apply generally. [source] Clinical practice experience with testosterone treatment in men with testosterone deficiency syndromeBJU INTERNATIONAL, Issue 9 2008Drew McLaren OBJECTIVE To report on a clinical practice series of testosterone-replacement therapy (TRT) in men with testosterone deficiency syndrome (TDS), examining clinical efficacy, biochemical parameters and effects on prostate health over a 2-year period. PATIENTS AND METHODS A retrospective review of 85 patients with symptoms of TDS and at least a 3-month trial of TRT was performed in this single-centre, clinical practice setting. Three domains of symptomatology were evaluated: libido, erectile function and energy levels. Symptoms were assessed by a combination of patient reporting, physician's assessment and validated symptom assessment scores. Total testosterone (TT), calculated bio-available testosterone (BT) and prostate-specific antigen (PSA) levels were continuously measured and effects on prostate health were examined. RESULTS Only 38 (45%) patients in this cohort remained on TRT for >2 years. The most common reason for discontinuing treatment was lack of clinical response but those remaining on TRT had continued improvement in libido, erectile function and energy levels. During treatment, the average TT and calculated BT values significantly increased compared with the baseline values at most of the evaluated time points, with no significant change in average PSA values. In all, 15% of this cohort had some degree of progression of lower urinary tract symptoms. Seven patients had eight ,for-cause' prostate biopsies either during supplementation or at any date after completion, with an only three positive for cancer. CONCLUSIONS Only 45% of men on TRT remained on treatment for >2 years in this clinical practice experience of men with TDS. Those remaining showed persistent improvement in their symptoms. The average TT and BT values increased significantly with no significant change in PSA levels. [source] Synthesis and transport of creatine in the CNS: importance for cerebral functionsJOURNAL OF NEUROCHEMISTRY, Issue 2 2010Elidie Béard J. Neurochem. (2010) 115, 297,313. Abstract Apart of its well known function of ,energetic buffer' through the creatine/phosphocreatine/creatine kinase system allowing the regeneration of ATP, creatine has been recently suggested as a potential neuromodulator of even true neurotransmitter. Moreover, the recent discovery of primary creatine deficiency syndromes, due to deficiencies in l -arginine : glycine amidinotransferase or guanidinoacetate methyltransferase (the two enzymes allowing creatine synthesis) or in the creatine transporter, has shed new light on creatine synthesis, metabolism and transport, in particular in CNS which appears as the main tissue affected by these creatine deficiencies. Recent data suggest that creatine can cross blood-brain barrier but only with a poor efficiency, and that the brain must ensure parts of its needs in creatine by its own endogenous synthesis. Finally, the recent years have demonstrated the interest to use creatine as a neuroprotective agent in a growing number of neurodegenerative diseases, including Parkinson's and Huntington's diseases. This article aims at reviewing the latest data on creatine metabolism and transport in the brain, in relation to creatine deficiencies and to the potential use of creatine as neuroprotective molecule. Emphasis is also given to the importance of creatine for cerebral function. [source] | ||||||||||||||||||||||||||||||||||||||||