Genome-wide scans for diabetic nephropathy and albuminuria in multiethnic populations: the family investigation of nephropathy and diabetes (FIND)

The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes.     

Phase II clinical trial with Praneem polyherbal tablets for assessment of their efficacy in symptomatic women with abnormal vaginal discharge (an ICMR task force study)

Abnormal vaginal discharge syndrome (AVDS) is a commonly observed gynaecological complaint for which women seek medical attention. The present study was conducted in six Indian Council of Medical Research centres with Praneem polyherbal tablets (PPT), to determine their efficacy in the treatment of symptomatic women with AVDS. Data are given on 141 subjects investigated. In total, 137 women (97%) reported complete (n=62, 44%) and partial (n=75, 53%) relief from symptoms after use of PPT for seven consecutive days. On speculum examination, 71 (74%) women were confirmed to be cured of AVDS. Microbiological tests could only be conducted microscopically for Trichomonas vaginalis, Candida albicans and bacterial vaginosis. It was observed that all women with T. vaginalis had this infection cured by PPT, and the cure rate was 77% for C. albicans and 68% for bacterial vaginosis. Seventy-eight women (55%) reported a transient burning sensation, mostly on the first 2 d of intake of PPT; however, they continued to use the tablets for the prescribed 7 d. This study lays the basis for an extended Phase II/III clinical trial, preferably randomized and comparing a larger number of women to confirm the safety and efficacy of PPT.     

Distribution trends of Salmonella serovars in India (2001-2005)

A total of 3079 samples were received and identified at the National Salmonella and Escherichia Centre (NSEC), Central Research Institute, Kasauli, India during 2001-2005. Out of these, 2098 samples were from humans, 250 from animals, and 726 from meat, vegetables, seafood and the environment. The Salmonella strains isolated were distributed among 35 different Salmonella serovars. The most common serovars from humans were Salmonella Typhi (73%) and Salmonella Paratyphi A (24%) among typhoidal serovars, and Salmonella Worthington (28.2%) and Salmonella Typhimurium (22.5%) among non-typhoidal serovars. The other frequently isolated serovars from different sources were Salmonella Gallinarum, Salmonella Typhimurium, Salmonella Enteritidis and Salmonella Dublin. Analysis of the prevalence of the 10 most common serovars in 18 states indicated that different serovars are distributed in different parts of India. The results from this study may be helpful in formulating preventive strategies to control the spread of infection in the country.     

Elucidating the role of hypoxia-inducible factor in rheumatoid arthritis

Inflammopharmacology - Rheumatoid arthritis (RA) is a chronic multifactorial disease, provocative, and degenerative autoimmune condition that impacts millions of individuals around the globe. As a...     

Epidermodysplasia verruciformis: 14 members of a pedigree with an intriguing squamous cell carcinoma transformation

A 38-year-old farmer was apparently well until 5 years of age. At this age, the patient's mother found mildly itchy, raised eruptions over the scalp during combing of the scalp hair. Since then, the eruptions have progressed insidiously to involve the face and other parts of the body, with a preponderance over the face, upper back, and chest, including the palms. The soles, oral cavity, and genital tract were unaffected. The lesions were persistent in nature and showed no remission or exacerbation. Mild to moderate pruritus/discomfort was experienced following sunlight exposure. A prominent, raised eruption appeared on the right side of the forehead 9 years ago, 25 years after the initial eruptions, which in due course ulcerated. It was progressive in nature and acquired a large size. Two years later, it was diagnosed as squamous cell carcinoma, for which liquid nitrogen cryosurgery was performed. There was a recurrence of the lesion at the site of surgery, which was excised 4 months later. Subsequently, there was a sudden flare up at the same site. It was badly infected with maggot infestation. The relentless course of the disease was evident by the appearance of two similar lesions, one on the right half of the nose and the other on the left preauricular region. A short while ago, fatigue and loss of weight were also recorded. Bladder and bowel functions were normal and there was no loss of appetite, hoarseness of voice, or breathlessness. Four of the patient's six children (three sons and one daughter) were reported to have similar lesions all over the body. In addition, nine other relatives were also affected. Accordingly, a total of 14 (12 males and two females) family members were found to be affected from amongst 41 individuals (26 males and 15 females) spread across several generations (Fig. 1). There was a second-degree consanguinity of marriage, with the patient's grandmother and wife's father being brother and sister. Skin surface examination was marked by multiple, discrete, flat-topped, scaly, brownish-black papules of diverse morphology, from hypopigmented macules to verrucous lesions, with a few coalescing to form plaques. The scales were brown, dry, and adherent (Fig. 2a). The lesions were conspicuous by their presence over the face, neck, and front and back of the chest. The extremities were also affected. Nevertheless, the soles and genitalia were spared. The oral mucosae, hair, and nails were normal. Koebner's phenomenon was explicit, whereas Auspitz's sign was not demonstrable. In addition, a perceptible nodulo-ulcerative lesion (size, 3 in x 2 in) with indurated, raised, averted margins was encountered on the right side of the forehead. The ulcer was tender and had a fetid discharge. Necrotic slough was prominent over its base. Similar lesions were located on the left preauricular region and right half of the nose. Hematoxylin and eosin-stained sections prepared from biopsies taken from representative lesions of epidermodysplasia verruciformis and squamous cell carcinoma revealed their diagnostic features. Epidermodysplasia verruciformis showed features of hyperkeratosis and acanthosis with hardly any papillomatosis. Marginal elongation of the rete ridges was present. Extensive vacuolization was a remarkable feature, and was largely confined to the upper stratum Malpighian and the granular cell layer. Some of the vacuolated cells were fairly large; their nuclei were located in the center and had variable pyknosis. The granular cell layer was uniformly thickened, whereas the stratum corneum had a loosely felted (basket-weave) appearance. The dermis was apparently normal (Fig. 2b,c). The other microsection(s) from squamous cell carcinoma were conspicuous by the presence of hyperkeratosis, acanthosis, and irregular masses of epidermal cells, proliferating downwards and invading the dermis. Varying proportions of differentiated squamous cells formed their bulk. These cells were atypical, characterized by variations in size and shape, hyperplasia and hyperchromasia of the nuclei, absence of prickles, chas, characterization of individual cells, and the presence of both mitotic and atypical mitotic figures (Fig. 3b).     

The prevalence of disability from chronic conditions due to injury among adults ages 18-69 years: United States, 1994

Purpose: To describe the causes and determine the prevalence of disability from chronic conditions due to injury among US civilian non-institutionalized persons aged 18-69 years. Methods: Data from the National Health Interview Survey Disability (NHIS-D) Supplement Phase I, United States 1994 were analysed and six disability categories were examined: activities of daily living (ADL), instrumental activities of daily living (IADL), functional activities (FA), sight, hearing, and communication. Results: In 1994, 5.6 million persons aged 18-69 years reported a disability because of a chronic condition that was caused by injury. The prevalence of ADL disability due to chronic conditions caused by injury was 370 per 100000 population; IADL disability was 1256; FA disability was 2512; sight was 231; hearing was 339; and communication was 91 per 100000 population. Fifty per cent of ADL, IADL, and FA disabilities were attributed to motor vehicle crashes and falls, as were 31% of sight, 19% of hearing, and 23% of communication disabilities. Conclusions: Though these estimates may be conservative, this study indicates that injury is a major cause of disability in addition to a leading cause of death in the US.