Lack of electron microscopy hinders correct renal biopsy diagnosis: A study from India

Electron microscopy (EM) is performed routinely on all native kidney biopsies in the western world. However, in India, it is not regularly performed due to non-availability and financial constraints. The aim of this prospective study was to evaluate the usefulness of routinely performing EM on native kidney biopsies. In order to eliminate selection bias, all consecutive native kidney biopsies were included in this study, provided they had adequate tissue for light, immunofluorescence (IF), and EM. The biopsies were reported on the basis of light and IF microscopy. EM was performed on each case by another pathologist who also independently reviewed the light microscopic slides and IF images. The findings were then reviewed to assess how the ultrastructural features contributed to the primary diagnosis and assigned to one of the following categories: 1. Crucial for diagnosis, 2. Important contribution, or 3. Not required. Of the 115 cases evaluated, EM was crucial in 12% of the cases. In 20% of the cases, it provided important confirmatory information and in the remaining 68% cases, EM was not considered required. This study supports the use of EM as a routine diagnostic tool in the evaluation of native kidney biopsies. There is an urgent need for availability and accessibility of EM in our country.     

Modulation of estrogen action during preimplantation period and in immature estradiol-primed rat uterus by anti-implantation agent, ormeloxifene

Studies were undertaken to evaluate the influence of estrogen antagonist-cum anti-implantation agent, ormeloxifene, on 17β-hydroxydsteroid dehydrogenase (17β-HSD) activity and estrogen action in rat uterus during preimplantation period and to examine its ability to induce progesterone receptor (PR) in immature rat model. A group of female rats received orally a contraceptive dose of 1.25 mg/kg of ormeloxifene on Day 1 postcoitum (pc). Rats were sacrificed on Days 3, 4 and 5 pc, and uterine tissues were processed for enzymatic, estrogen receptor and estradiol (E₂) estimations. Immature ovariectomized rats received ormeloxifene, subcutaneously for 3 days at various doses in the absence or presence of estradiol, and uterine PR levels were measured using ³H-R5020 as radioligand.

Results revealed that ormeloxifene treatment caused a marked increase in enzyme activity of 17β-HSD on Days 3, 4 and 5 pc as compared to respective controls. Further, total uterine estrogen receptors as estimated by exchange assay showed a noticeable decrease on Days 4 (35%) and 5 (>80%) pc in ormeloxifene-treated groups. The results correlated well with a decrease in tissue E₂ levels. In immature rats, ormeloxifene caused a dose-dependent increase in cytosolic PR levels; ormeloxifene given along with E₂ (0.1 μg) for 3 days caused a significant reduction in concentration of PRs at 10 μg and higher doses.

Ormeloxifene also induced ³H-progesterone (P) uptake by immature rat uterus. However, in the presence of E₂, it significantly reduced ³H-P uptake. The in vitro competitive binding experiments did not reveal any displacement of ³H-R5020 either by ormeloxifene or by its hydroxy derivative from PR. The results suggest that in addition to its competitive antagonism at estrogen receptor level, ormeloxifene enhances the inactivation of intracellular E₂ to estrone, a biologically less active form, thus declining estrogen receptor pool. Moreover, it causes indirect anti-progestational effects in the uterus by virtue of its anti-estrogenic profile rather than by blocking the PRs.     

Nucleotide correlation between HAV isolates from human patients and environmental samples

Hepatitis A disease is endemic in Albania even though records from the Medical Authority show outbreaks involving only limited numbers of people. In the city of Lac, 200 people became ill following an outbreak of hepatitis A started on November 2002. The age distribution of the cases shows a peak in the age group 5-9 (43.5%) followed by the age group 10-14 (28%) and the age group 1-4 (18%). No cases were recorded in the age group 0-1. Drinking water and sewage samples were collected, using electropositive cartridges, during the outbreak. Rotavirus was identified by RT-PCR in two out of five drinking water samples; however, all the samples tested negative for HAV and astrovirus. Rotavirus was also identified in three out of five sewage samples from which four were HAV positive. HAV-RNA was identified in 28 (62.2%) out of 45 IgM anti-HAV positive sera collected during the outbreak. Genotype IA was expressed from all the amplified samples. Sequence analysis of the overlapping VP1-2A region shows 97-99% homology with three Italian strains IT-SCH-00, IT-ZAM-01, and IT-CAP-00 and one Spanish strain (Sa 30/06/95), whereas the phylogenetic tree built from the 168 bp sequence of the VP1-2A shows four clusters, one including 24 out of 28 RT-PCR positive sera. Considering the deduced amino acid sequence, only one substitution was identified and reported previously for genotype IB.     

Severe toxicity following induction chemotherapy for acute myelogenous leukemia in a patient with Werner's syndrome

Werner's syndrome is an autosomal recessive disorder resulting in premature aging. Most patients die in their fifth decade from malignancies or heart disease. The gene for Werner's syndrome (WRN) encodes a recQ helicase. Cells from patients with Werner's syndrome have increased sensitivity to DNA-damaging drugs in vitro. Here we present a patient with Werner's syndrome who developed severe chemotherapy-induced toxicity during treatment for acute myelogenous leukemia. We propose that lack of WRN resulted in increased sensitivity of the patient's cells to the toxicity of chemotherapy.     

Acute carpal tunnel syndrome from burns of the hand and wrist

Acute median nerve compression usually occurs from increased pressure within the carpal tunnel and forearm compartments. Although the hyperesthesia from burns may mimic symptoms of acute compression neuropathy, clinical diagnosis should be made from history, clinical signs and symptoms. Early recognition and decompression of the carpal tunnel either as part of the burn excision or along with escharotomy usually leads to full recovery.     

Familial social support and depression in breast cancer: an exploratory study on a Pakistani sample

This exploratory study investigated the relationship between familial social support and depression in a Pakistani sample of 80 female breast cancer patients, and whether the groups of demographic and medical variables differ on the levels of familial social support and depression. Familial social support and depression were measured by indigenous scales administered in Urdu language and found to be significantly inversely correlated. The groups based on age, number of children, financial sources of treatment, and disease stage differed significantly on familial social support and depression. No significant group differences were found on familial social support and depression between the groups of patients living in joint and nuclear families, and those who had and had not undergone mastectomy. Results are discussed in the respective social and cultural context.     

The relation between mitral annular calcification and mortality in patients undergoing diagnostic coronary angiography

To determine whether the observed association between mitral annular calcification (MAC) and mortality is independent of the severity of coronary artery disease (CAD), we analyzed data from 134 male veterans (age 63 +/- 10 years) followed for 5 years who had undergone diagnostic coronary angiography and transthoracic echocardiography within 6 months of each other. Echocardiograms were retrospectively reviewed for the presence of MAC. The relation of MAC to all-cause mortality was analyzed using logistic regression, and odds ratios (OR) were calculated. MAC was present in 49 (37%) subjects. Over the 5-year follow-up period, 38 (28%) patients expired. Five-year survival was 80% for subjects without MAC and 56% for subjects with MAC (P = 0.003). MAC (OR = 3.16, 95% confidence interval [CI]= 1.43-6.96, P = 0.003), ejection fraction (OR = 0.76, 95% CI = 0.59-0.97, P = 0.02), and left main CAD (OR = 2.70, 95% CI = 1.11-6.57, P = 0.02) were significantly associated with mortality in univariate analysis. After adjusting for left ventricular ejection fraction, number of obstructed coronary arteries and the presence of left main coronary artery stenosis, MAC significantly predicted death (OR = 2.48, 95% CI = 1.09-5.68, P = 0.03). Similarly, after adjusting for predictors of MAC, including ejection fraction, age, diabetes, peripheral vascular disease, and heart failure, MAC remained a significant predictor of death (OR = 2.38, 95% CI = 1.02-5.58, P = 0.04). MAC also predicted death independent of smoking status, hypertension, serum creatinine, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and C-reactive protein levels (OR = 3.98, 95% CI = 1.68-9.40, P = 0.001). MAC detected by two-dimensional echocardiography independently predicts mortality and may provide an easy-to-perform and inexpensive way to improve risk stratification.