Evaluation of the profile of alopecia areata and the prevalence of thyroid function test abnormalities and serum autoantibodies in Iranian patients

BACKGROUND: The study aimed at evaluating the prevalence of thyroid function abnormalities in patients with alopecia areata (AA) and its association with other autoimmune diseases and various autoimmune antibodies. METHOD: We retrospectively analyzed medical records of 123 patients with AA. The main site of involvement, pattern, and extent of alopecia as well as presence of the similar disease in first-degree family members and serologic status of patients were recorded. RESULTS: Participating in the study were 57 males and 66 females (6 to 59 years old). In the majority of patients (69.9%) the disease was manifested in the first two decades of life. Patients with family members having alopecia were recorded in 24.4%. Thyroid function abnormalities were found in 8.9% of patients. Positive autoimmune antibodies were associated with AA in 51.4% of patients with no significant association between the severity and duration of disease and presence of these antibodies. CONCLUSION: The incidence of positive auto-immune antibodies in Iranian patients is higher than previous reports. Concerning the female:male ratio, thyroid function tests and the prevalence of alopecia in first-degree relatives, our results are compatible with previous data obtained from different ethnic populations. Previous reports documented that a greater severity and longer duration of AA were seen in the early onset forms; however our result are relatively different which could be explained by differences in genetic factors

Partial volume correction strategies for quantitative FDG PET in oncology

Purpose: Quantitative accuracy of positron emission tomography (PET) is affected by partial volume effects resulting in increased underestimation of the standardized uptake value (SUV) with decreasing tumour volume. The purpose of the present study was to assess accuracy and precision of different partial volume correction (PVC) methods. Methods: Three methods for PVC were evaluated: (1) inclusion of the point spread function (PSF) within the reconstruction, (2) iterative deconvolution of PET images and (3) calculation of spill-in and spill-out factors based on tumour masks. Simulations were based on a mathematical phantom with tumours of different sizes and shapes. Phantom experiments were performed in 2-D mode using the National Electrical Manufacturers Association (NEMA) NU2 image quality phantom containing six differently sized spheres. Clinical studies (2-D mode) included a test-retest study consisting of 10 patients with stage IIIB and IV non-small cell lung cancer and a response monitoring study consisting of 15 female breast cancer patients. In all studies tumour or sphere volumes of interest (VOI) were generated using VOI based on adaptive relative thresholds. Results: Simulations and experiments provided similar results. All methods were able to accurately recover true SUV within 10% for spheres equal to and larger than 1 ml. Reconstruction-based recovery, however, provided up to twofold better precision than image-based methods. Cl

SAVVY Vaginal Gel (C31G) for Prevention of HIV Infection: A Randomized Controlled Trial in Nigeria

The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk.This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1 ratio 1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use.SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY

Fatal cerebral edema associated with serine deficiency in CSF

Two young girls without a notable medical history except for asthma presented with an acute toxic encephalopathy with very low serine concentrations both in plasma and cerebrospinal fluid (CSF) comparable to patients with 3-phosphoglycerate dehydrogenase (3-PGDH) deficiency. Clinical symptoms and enzyme measurement (in one patient) excluded 3-PGDH deficiency. Deficiencies in other serine biosynthesis enzymes were highly unlikely on clinical grounds. On basis of the fasting state, ketone bodies and lactate in plasma, urine and CSF, we speculate that reduced serine levels were due to its use as gluconeogenic substrate, conversion to pyruvate by brain serine racemase or decreased L-serine production because of a lack of glucose. These are the first strikingly similar cases of patients with a clear secondary serine deficiency associated with a toxic encephalopathy

Genetic variation exists for telomeric array organization within and among the genomes of normal, immortalized, and transformed chicken systems

This study investigated telomeric array organization of diverse chicken genotypes utilizing in vivo and in vitro cells having phenotypes with different proliferation potencies. Our experimental objective was to characterize the extent and nature of array variation present to explore the hypothesis that mega-telomeres are a universal and fixed feature of chicken genotypes. Four different genotypes were studied including normal (UCD 001, USDA-ADOL Line 0), immortalized (DF-1), and transformed (DT40) cells. Both cytogenetic and molecular approaches were utilized to develop an integrated view of telomeric array organization. It was determined that significant variation exists within and among chicken genotypes for chromosome-specific telomeric array organization and total genomic-telomeric sequence content. Although there was variation for mega-telomere number and distribution, two mega-telomere loci were in common among chicken genetic lines (GGA 9 and GGA W). The DF-1 cell line was discovered to maintain a complex derivative karyotype involving chromosome fusions in the homozygous and heterozygous condition. Also, the DF-1 cell line was found to contain the greatest amount of telomeric sequence per genome (17%) as compared to UCD 001 (5%) and DT40 (1.2%). The chicken is an excellent model for studying unique and universal features of vertebrate telomere biology, and characterization of the telomere length variation among genotypes will be useful in the exploration of mechanisms controlling telomere length maintenance in different cell types having unique phenotypes

Cytotoxic T-cell precursor frequencies to HER-2 (369 – 377) in patients with HER-2/neu-positive epithelial tumours

HER-2/neu oncoprotein contains several major histocompatibility complex class I-restricted epitopes, which are recognised by cytotoxic T lymphocyte (CTL) on autologous tumours and therefore can be used in immune-based cancer therapies. Of these, the most extensively studied is HER-2(9(369)). In the present report, we used dendritic cells pulsed with HER-2(9(369)) to stimulate, in the presence of IL-7 and IL-12, the production of IFN-gamma by patients' CTL detected by the enzyme-linked immunosorbent spot-assay. Frequencies of peptide-specific precursors were estimated in HLA-A2, HLA-A3 and HLA-A26 patients with HER-2/neu-positive (+) breast, ovarian, lung, colorectal and prostate cancers and healthy individuals. We found increased percentages of such precursors in HLA-A2 (25%) and HLA-A26 (30%) patients, which were significantly higher (60%) in HLA-A3 patients. Our results demonstrate for the first time that pre-existing immunity to HER-2(9(369)) occurs in patients with colorectal, lung and prostate cancer. They also suggest that HER-2(9(369)) can be recognised by CTL, besides HLA-A2, also in the context of HLA-A3 and HLA-A26, thus increasing the applicability of HER-2(9(369))-based vaccinations in a considerably broader patients' population.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Vaccination with human anti-trastuzumab anti-idiotype scFv reverses HER2 immunological tolerance and induces tumor immunity in MMTV.f.huHER2(Fo5) mice

International audienceINTRODUCTION: Novel adjuvant therapies are needed to prevent metastatic relapses in HER2-expressing breast cancer. Here, we tested whether trastuzumab-selected single-chain Fv (scFv) could be used to develop an anti-idiotype-based vaccine to inhibit growth of HER2-positive tumor cells in vitro and in vivo through induction of long-lasting HER-specific immunity. METHODS: BALB/c mice were immunized with anti-trastuzumab anti-idiotype (anti-Id) scFv (scFv40 and scFv69), which mimic human HER2. Their sera were assessed for the presence of HER2-specific Ab1' antibodies and for their ability to reduce viability of SK-OV-3 cells, a HER2-positive cancer cell line, in nude mice. MMTV.f.huHER2(Fo5) transgenic mice were immunized with scFv40 and scFv69 and, then, growth inhibition of spontaneous HER2-positive mammary tumors, humoral response, antibody isotype as well as splenocyte secretion of IL2 and IFN-γ were evaluated. RESULTS: Adoptively-transferred sera from BALB/c mice immunized with scFv40 and scFv69 contain anti-HER2 Ab1' antibodies that can efficiently inhibit growth of SK-OV-3 cell tumors in nude mice. Similarly, prophylactic vaccination with anti-Id scFv69 fully protects virgin or primiparous FVB-MMTV.f.huHER2(Fo5) females from developing spontaneous mammary tumors. Moreover, such vaccination elicits an anti-HER2 Ab1' immune response together with a scFv69-specific Th1 response with IL2 and IFN-γ cytokine secretion. CONCLUSIONS: Anti-trastuzumab anti-Id scFv69, used as a therapeutic or prophylactic vaccine, protects mice from developing HER2-positive mammary tumors by inducing both anti-HER2 Ab1' antibody production and an anti-HER2 Th2-dependent immune response. These results suggest that scFv69 could be used as an anti-Id-based vaccine for adjuvant therapy of patients with HER2-positive tumors to reverse immunological tolerance to HER2

Health care access dimensions and cervical cancer screening in South Africa: analysis of the world health survey.

Background Cervical cancer is the most commonly diagnosed cancer and the leading cause of cancer mortality among women in sub-Saharan Africa. Recent recommendations for cervical cancer primary prevention highlight HPV vaccination, and secondary prevention through screening. However, few studies have examined the different dimensions of health care access, and how these may influence screening behavior, especially in the context of clinical preventive services. Methods Using the 2003 South Africa World Health Survey, we determined the prevalence of cervical cancer screening with pelvic examinations and/or pap smears among women ages 18 years and older. We also examined the association between multiple dimensions of health care access and screening focusing on the affordability, availability, accessibility, accommodation and acceptability components. Results About 1 in 4 (25.3%, n = 65) of the women who attended a health care facility in the past year got screened for cervical cancer. Screened women had a significantly higher number of health care providers available compared with unscreened women (mean 125 vs.12, p-value Conclusions Our findings suggest that cost issues (affordability component) and other patient level factors (captured in the acceptability, accessibility and accommodation components) were less important predictors of screening compared with availability of physicians in this population. Meeting cervical cancer screening and HPV vaccination goals will require significant investments in the health care workforce, improving health care worker density in poor and rural areas, and improved training of the existing workforce