Predictors of death in under-five children with diarrhoea admitted to a critical care ward in an urban hospital in Bangladesh

Aim : To evaluate the clinical and laboratory predictors of death in hospitalized under‐five children with diarrhoea. Methods : This is a prospective cohort study carried out in the Special Care Ward (SCW) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh. All admitted diarrhoeal children of both sexes, aged 0–59 months, from September 2007 through December 2007 were enrolled. We compared and analysed factors among diarrhoeal children who died (n = 29) with those who survived (n = 229). Results : In logistic regression analysis, after adjusting for potential confounders (infusion of intravenous fluid and immature PMN), absent peripheral pulse even after complete rehydration (OR 10.9, 95% CI 2.1–56.8; p < 0.01), severe malnutrition (OR 7.9, 95% CI 1.8–34.8; p < 0.01), hypoxaemia (OR 8.5, 95% CI 1.0‐75.0; p = 0.05), radiological lobar pneumonia (OR 17.8, 95% CI 3.7–84.5; p < 0.01) and hypernatraemia (OR 15.8, 95% CI 3.0–81.8; p < 0.01) were independently associated with deaths among diarrhoeal children admitted to SCW. Conclusions:  Thus, the absence of peripheral pulses even after full rehydration, severe malnutrition, hypoxaemia, lobar pneumonia and hypernatraemia are independent predictors of death among the under‐five children with diarrhoea admitted to critical care ward of a resource‐limited setting in Bangladesh.     

Analytical performance evaluation of a new turbidimetric immunoassay for valproic acid on the ADVIA 1650 analyzer: effect of gross hemolysis and high bilirubin

Valproic acid is an anticonvulsant that requires careful therapeutic drug monitoring. Valproic acid is also used in psychiatric patients. Bayer Diagnostics (Tarrytown, NY) recently marketed a turbidimetric immunoassay for monitoring valproic acid concentrations in serum or plasma using the ADVIA 1650 analyzer. We evaluated the performance of this new assay by comparing it with a widely used fluorescence polarization immunoassay (FPIA) on the AxSYM analyzer (Abbott Laboratories, Abbott Park, IL). The total coefficient of variation (CV) for the low control of this new assay was 6.8% (mean = 30.7, SD = 2.1 microg/mL, n = 44) while the corresponding CVs for the medium and high controls were 3.3% (mean = 81.0, SD = 2.7 microg/mL, n = 44) and 5.9% (mean = 142.9, SD = 8.4 microg/mL, n = 44), respectively. The assay is linear up to a serum valproic acid concentration of 170 microg/mL, and the detection limit is 4.4 microg/mL. We observed an excellent correlation between the FPIA of valproic acid and the turbidimetric assay using specimens from 52 different patients who were receiving valproic acid. Using the valproic acid concentrations obtained by the FPIA as the x-axis, and the corresponding valproic acid concentrations obtained by the turbidimetric assay as the y-axis, we developed the following regression equation: y = 1.03 x+1.55 (r = 0.98). With this new assay, high concentrations of bilirubin (unconjugated 30 mg/dL and conjugated 30 mg/dL) and gross hemolysis (4+, hemoglobin: 1,500 mg/dL) have no effect on measurements of valproic acid concentration. We conclude that the new turbidimetric assay for valproic acid can be used for routine therapeutic drug monitoring of valproic acid in clinical laboratories.     

Importance of peripheral biopsies in maximising the detection of early prostate cancer in repeat 12-core biopsy protocols

OBJECTIVE: To assess cancer-detection rates in repeat 12-core biopsy protocols, as extended multicore prostate biopsy protocols have become standard when investigating men with a raised prostate-specific antigen (PSA) level, but repeat prostate biopsy protocols are still developing. PATIENTS AND METHODS: During a 4.5-year period, 241 of 590 patients with persistently high age-specific PSA levels of 2.6-10 ng/mL and an initial benign biopsy were invited for repeat transrectal ultrasonography-guided 12-core prostatic biopsy. The protocol for repeat biopsy was identical to the first biopsy, and included a periprostatic nerve block. The first six biopsies were obtained from the periphery of the gland directed more laterally at the base, mid-zone and apices. The remainder were parasagittal sextant biopsies. Pathological findings were analysed on an individual core basis. RESULTS: The mean age of the 241 men was 63.4 years; cancer was diagnosed in 40 (16.6%) on repeat biopsy. Men with cancer were older and had a higher median PSA level. The median Gleason score was 6, with a median of two cores positive for cancer. Maximum cancer detection rates were from peripheral apices (37.5%), basal biopsies had the lowest detection rates (23.8% and 16.3%), and parasagittal biopsies missed 35% of detected cancers. Patients with cancer also had significantly lower prostate volumes and higher PSA densities (both P < 0.001). CONCLUSION: A low cancer yield from both peripheral basal and parasagittal basal specimens on repeat biopsy indicates adequate sampling at initial biopsy. The maximum cancer yield in the peripheral mid-zones and apical zones suggests the necessity for concentrated sampling of these zones in repeat biopsy protocols.     

A modified whole blood partial thromboplastin test for the assessment of heparinization

Current methods of assessment of heparinization are either inconvenient as bedside procedures or lack correlation with the Lee-White whole blood clotting time over the therapeutic range. A new thromboplastin time (CAT time) has been developed to overcome these disadvantages by offering uniform contact activation. The test makes use of a partial thromboplastin activated by celite-adsorbed “contact factor”, thus eliminating the activation phase of the activated partial thromboplastin time. Preliminary experiments suggest that this modification will be helpful in the study of “contact factor” deficiencies.     

Pendred’s syndrome

A case of Pendred’s syndrome is described. It appears that Pendred’s syndrome is due to the Pleotropic effect of one gene.     

Cooperation between FGF8b overexpression and PTEN deficiency in prostate tumorigenesis

Two commonly occurring genetic aberrations of human prostate cancer [i.e., overexpression of a mitogenic polypeptide (fibroblast growth factor 8, isoform b or FGF8b) and loss of function of PTEN tumor suppressor] were recapitulated into a new combinatorial mouse model. This model harboring the Fgf8b transgene and haploinsufficiency in Pten, both in a prostate epithelium-specific manner, yielded prostatic adenocarcinoma with readily detectable lymph node metastases, whereas single models with each of the defects were shown earlier to progress generally only up to prostatic intraepithelial neoplasia (PIN). In addition to late age-related development of typical adenocarcinoma, the model also displayed a low incidence of mucinous adenocarcinoma, a rare variant type of human prostatic adenocarcinoma. The cooperation between FGF8b activation and PTEN deficiency must be linked to acquisition of additional genetic alterations for the progression of the lesions to primary adenocarcinoma. Here, we identified loss of heterozygosity at the Pten gene leading to bialleic loss, as a necessary secondary event, indicating that a complete loss of PTEN function is required in the development of invasive cancer in the model. Analyses of expression of downstream mediators phospho-AKT (p-AKT) and p27(KIP1), in various types of lesions, however, revealed a complex picture. Although PIN lesions displayed relatively strong expression of p-AKT and p27(KIP1), there was a notable heterogeneity with variable decrease in their immunostaining in adenocarcinomas. Together, the results further underscore the notion that besides activation of AKT by loss of PTEN function, other PTEN-regulated pathways must be operative for progression of lesions from PIN to adenocarcinoma.