Do children with primary nocturnal enuresis have a retarded bone age? A cross‐sectional study

OBJECTIVE: Nocturnal enuresis is a common pediatric problem, the etiology of which is unclear. In recent years, various studies have been published stating that children with nocturnal enuresis exhibit growth and skeletal maturation retardation. METHODS: In this cross-sectional study, we included 27 patients (16 boys, 11 girls) between the ages of 6 and 14 years who had presented with primary nocturnal enuresis (PNE) complaints. We included in the evaluation 19 healthy subjects (12 boys, 7 girls), who were the siblings of the children with PNE, as the control group. RESULTS: The patients in both groups were similar in chronological age, bone age, height and weight, with no significant difference between groups (P>0.05). CONCLUSION: The two groups in our study consisted of the same genetic background. Thus, our results were found to be different from the previous studies. We have concluded that there is no direct relationship between enuresis nocturnal and skeletal maturation.     

THE IMPACT OF PRE-CLERKING CLINICS ON SURGICAL OPERATION CANCELLATIONS: A PROSPECTIVE AUDIT

Pre-clerking of all patients undergoing elective general surgical operations was introduced at our hospital in an attempt to reduce an unacceptably high operation cancellation rate. A prospective audit has been performed on the effect of this policy on the cancellation rate. Before the introduction of pre-clerking there was a marked seasonal variation in the number of patients who failed to attend for surgery, which could be explained by absence on holiday. This seasonal variation disappeared after the start of pre-clerking clinics, but there has been no reduction in the number of cancellations for medical reasons.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.      

Tumor necrosis factor-alpha is expressed by glomerular visceral epithelial cells in human membranous nephropathy.

The role of tumor necrosis factor alpha (TNF-alpha) was examined in biopsy-proven glomerulonephritis by immunohistochemistry, in situ hybridization, immunogold electron microscopy, immunoassay in serum and urine, and urinary immunoblot. Striking glomerular capillary wall and visceral glomerular epithelial cell TNF-alpha protein staining was observed in all cases of membranous nephropathy and membranous lupus nephropathy. Staining was less frequently observed in crescentic glomerulonephritis and in isolated cases of other histological subtypes of glomerulonephritis, usually in association with glomerular macrophages. By immunogold electron microscopy TNF-alpha was localized in membranous nephropathy within the visceral glomerular epithelial cells, and also in the glomerular basement membrane, especially in relation to immune deposits. In situ hybridization localized TNF-alpha mRNA exclusively to glomerular epithelial cells in all biopsies with membranous morphology but not in other histological subtypes. Concentrations of TNF-alpha were significantly increased compared with normal controls in the urine of patients with membranous nephropathy and with crescentic glomerulonephritis. The expression of TNF-alpha by glomerular epithelial cells exclusively and universally in biopsies showing a membranous morphology strongly suggests this cytokine has a role in the pathogenesis of membranous nephropathy.     

Development and characterisation of neutralising monoclonal antibody to the SARS-coronavirus

There is a global need to elucidate protective antigens expressed by the SARS-coronavirus (SARS-CoV). Monoclonal antibody reagents that recognise specific antigens on SARS-CoV are needed urgently. In this report, the development and immunochemical characterisation of a panel of murine monoclonal antibodies (mAbs) against the SARS-CoV is presented, based upon their specificity, binding requirements, and biological activity. Initial screening by ELISA, using highly purified virus as the coating antigen, resulted in the selection of 103 mAbs to the SARS virus. Subsequent screening steps reduced this panel to seventeen IgG mAbs. A single mAb, F26G15, is specific for the nucleoprotein as seen in Western immunoblot while five other mAbs react with the Spike protein. Two of these Spike-specific mAbs demonstrate the ability to neutralise SARS-CoV in vitro while another four Western immunoblot-negative mAbs also neutralise the virus. The utility of these mAbs for diagnostic development is demonstrated. Antibody from convalescent SARS patients, but not normal human serum, is also shown to specifically compete off binding of mAbs to whole SARS-CoV. These studies highlight the importance of using standardised assays and reagents. These mAbs will be useful for the development of diagnostic tests, studies of SARS-CoV pathogenesis and vaccine development.     

Ameliorating effect of microdoses of a potentized homeopathic drug,Arsenicum Album,on arsenic-induced toxicity in mice

Background  

Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols.     

A mathematical model of optimized radioiodine-131 therapy of Graves' hyperthyroidism

Background

The current status of radioiodine-131 (RaI) dosimetry for Graves' hyperthyroidism is not clear. Recurrent hyperthyroidism and iatrogenic hypothyroidism are two problems which interact such that trying to solve one leads to exacerbation of the other. Optimized RaI therapy has therefore begun to be defined just in terms of early hypothyroidism (ablative therapy) as physicians have given up on reducing hypothyroidism.

Methods

Optimized therapy is evaluated both in terms of the greatest separation of cure rate from hypothyroidism rate (non-ablative therapy) or in terms of early hypothyroidism (ablative therapy) by mathematical modeling of outcome after radioiodine and critically discussing the three common methods of RaI dosing for Graves' disease.

Results

Cure follows a logarithmic relationship to activity administered or absorbed dose, while hypothyroidism follows a linear relationship. The effect of including or omitting factors in the calculation of the administered I–131 activity such as the measured thyroid uptake and effective half-life of RaI or giving extra compensation for gland size is discussed.

Conclusions

Very little benefit can be gained by employing complicated methods of RaI dose selection for non-ablative therapy since the standard activity model shows the best potential for cure and prolonged euthyroidism. For ablative therapy, a standard MBq/g dosing provides the best outcome in terms of cure and early hypothyroidism.     

Interleukin-10 inhibits experimental mesangial proliferative glomerulonephritis

Conflicting reports exist regarding the effects of interleukin-10 (IL-10) on mesangial cells. There have been reports of both proliferative and antiproliferative effects, and both proinflammatory and anti-inflammatory effects of IL-10 on mesangial cells. However, the potential for IL-10 to affect glomerulonephritis characterized by mesangial proliferation is not known. To test the hypothesis that IL-10 would limit experimental mesangial proliferative glomerulonephritis, IL-10 was administered to rats in which mesangial proliferative glomerulonephritis was induced by administration of anti-Thy 1 antibody. Compared to control treated rats, IL-10 treated rats showed less proliferation, with fewer cells in glomeruli. Glomerular cellular proliferation was reduced, assessed by the numbers of cells within glomeruli expressing either proliferating cell nuclear antigen (PCNA) or bromodeoxyuridine. Glomerular macrophage influx (but not the proportion of glomerular macrophages that were PCNA positive) was reduced by IL-10 administration. There was no significant reduction in glomerular alpha-smooth muscle actin staining. IL-10 treatment resulted in reduced renal IL-1beta mRNA expression and reduced glomerular ICAM-1 expression, but renal expression of MCP-1 and osteopontin mRNA was unaltered. This study demonstrates that in experimental mesangial proliferative glomerulonephritis IL-10 diminishes inflammatory cell recruitment and mesangial cell proliferation. The effects of IL-10 in inhibiting mesangial cell proliferation are likely to be due to a combination of direct effects of IL-10 on mesangial cells and effects mediated by macrophages.