Effect of nisoldipine on priming and activation of the human neutrophil respiratory burst

Nisoldipine inhibits calcium (Ca⁺⁺) influx in human neutrophils: Preincubation with the dihydropyridine, nisoldipine (1.5 M) resulted in a 30% decrease in^[45]Ca⁺⁺ influx during formyl-methionineleucine-phenylalanine (FMLP) stimulation in primed as well as resting cells. Although the drug does not inhibit Ca⁺⁺ dependent effector functions elicited by FMLP, e.g. superoxide (O ₂ ^– ) production, it inhibits FMLP priming, a phenomenon that is independent, of extracellular Ca⁺⁺. Nisoldipine, exhibited a narrow dose response with an ED₅₀ of ca. 1 M and total inhibition of primedO2/– response at 1.5 M. Nisoldipine (1.5 M) also abolished the incremental rise of Ca⁺⁺ _i in primed neutrophils stimulated with FMLP. The dissociation of nisoldipine inhibitory effects on cell effector function and Ca⁺⁺ transport were corroborated in studies with neutrophils stimulated with influenza virus and phorbol myristate acetate (PMA), stimuli which do not exhibit an extracellular Ca⁺⁺-dependence in their elicited responses. Unlike in FMLP-stimulated cells, nisoldipine reduced influenza virus and PMA initiated respiratory burst, indicating that this drug has inhibitory effects on neutrophil function independent of its effect on Ca⁺⁺ metabolism. Possible sites of action are postulated at phospholipase A₂ or calmodulin-regulated activities. Caution is thus required in interpreting the effects of dihydropyridine on cell function, when the drug is used at micromolar concentration.This work was supported in part by NIH grants NIAID 20064, NIHDK 37105 and training grant HL07501.     

Reference values of ECG parameters derived from 906 echocardiographically confirmed healthy Indian children: A population-based study from Gujarat

Introduction

There are few published studies on reference ranges of ECG parameters in children; some ethnic differences have been described.

Clinical and bacteriological profile of the ear in otogenic tetanus: a case control study.

Twenty two patients presented with otogenic tetanus. Seventeen patients had acute histories with only a single episode of otitis media with otorrhoea. Fifteen patients had unilateral central perforations, five had bilateral central perforations and two had no perforations but had acutely congested tympanic membranes which were bulging suggesting the presence of purulent fluid behind them. All patients with perforations had a purulent pulsatile discharge. A coexisting aerobic infection was seen in 85 per cent of the cultures and 59 per cent of these were due to staphylococcus aureus (versus 25 per cent in the controls). Only one patient had received partial immunization. Tetanus resulting from otitis media is not an indication for surgery.     

Predicting the reduction of parasitaemia following exchange transfusion in severe Plasmodium falciparum malaria: comparison of two mathematical formulae

Two mathematical models to predict the level of parasitaemia after exchange transfusion in severe malaria have been described. One formula, described by Wilkinson and colleagues, calculates the level from the total volume of blood exchanged whereas the other, derived by Van den Ende and colleagues, is recursive and gives estimates of the reduction in parasitaemia after each aliquot of exchange. The accuracies of predictions based on these two formulae were compared using data collected from 20 patients undergoing partial exchange transfusion (40 ml blood/kg body weight). The transfusions led to significant changes in the mean (S.D.) haemoglobin concentrations, which rose from 8.9 (2.4) to 10.1 (1.5) g/dl, and in the median levels of parasitaemia, which fell from 16.5% (interquartile range = 12.8%-28.8%) to 4.5% (interquartile range = 1.2%-9.3%). The median level of post-transfusion parasitaemia predicted by the Van den Ende formula (6.6%, with an interquartile range of 4.5%-10.2%) was similar to that observed, whereas that predicted by the Wilkinson formula (7.2%, with an interquartile range of 5.6%-12.4%) was significantly higher (P = 0.018). However, the median difference between the predictions based on the two formulae was represented by a parasitaemia of only 1.0% (interquartile range = 0.6%-1.85%). Thus, although the Van den Ende formula is more accurate than the Wilkinson, the difference is unlikely to be clinically significant.     

Prediction of mortality in an Indian intensive care unit

Objective To compare hospital outcome prediction using an artificial neural network model, built on an Indian data set, with the APACHE II (Acute Physiology and Chronic Health Evaluation II) logistic regression model.Design Analysis of a database containing prospectively collected data.Setting Medical-neurological ICU of a university hospital in Mumbai, India.Subjects Two thousand sixty-two consecutive admissions between 1996 and1998.Interventions None.Measurements and results The 22 variables used to obtain day-1 APACHE II score and risk of death were recorded. Data from 1,962 patients were used to train the neural network using a back-propagation algorithm. Data from the remaining 1,000 patients were used for testing this model and comparing it with APACHE II. There were 337 deaths in these 1,000 patients; APACHE II predicted 246 deaths while the neural network predicted 336 deaths. Calibration, assessed by the Hosmer-Lemeshow statistic, was better with the neural network (=22.4) than with APACHE II (=123.5) and so was discrimination (area under receiver operating characteristic curve =0.87 versus 0.77, p=0.002). Analysis of information gain due to each of the 22 variables revealed that the neural network could predict outcome using only 15 variables. A new model using these 15 variables predicted 335 deaths, had calibration (=27.7) and discrimination (area under receiver operating characteristic curve =0.88) which was comparable to the 22-variable model (p=0.87) and superior to the APACHE II equation (p<0.001).Conclusion Artificial neural networks, trained on Indian patient data, used fewer variables and yet outperformed the APACHE II system in predicting hospital outcome.Electronic Supplementary Material Supplementary material is available in the online version of this article at Part of this work was presented at the Sixth Annual Critical Care Congress of the Indian Society for Critical Care Medicine, Bangalore, India     

Benzathine penicillin, metronidazole and benzyl penicillin in the treatment of tetanus: a randomized, controlled trial

Penicillin, the drug of choice in tetanus, may potentiate the effect of tetanus toxin by inhibiting the type-A (GABAA) receptor for gamma-amino-n-butyric acid. Metronidazole has therefore been suggested as an alternative. Intramuscular benzathine penicillin (1.2 million units as a single dose; N=56), enteral metronidazole (600 mg every 6 h for 10 days; N=55) and intravenous benzyl penicillin (2 million units every 4 h for 10 days; N=50) were therefore compared, in a randomized, controlled trial, among patients with all grades of tetanus. On presentation, the three treatment groups were similar in terms of age and sex distributions, immune statuses, durations of illness, and their APACHE-II scores and Ablett's grades of tetanus. Of the patients given benzathine penicillin, 36 required tracheostomy, 10 neuromuscular blockade, and 23 mechanical ventilation; the corresponding numbers for the metronidazole (34, 12 and 18, respectively) and benzyl-penicillin groups (39, 12 and 25, respectively) were similar (P>0.10). The incidences of dysautonomia and nosocomial pneumonia and the numbers of in-hospital deaths (26 with benzathine penicillin, 19 with metronidazole and 22 with benzyl penicillin; P=0.392) were also similar in each treatment arm. The length of the hospital stay was longer in the patients receiving benzyl penicillin than in the benzathine-penicillin or metronidazole groups, with means (S.D.) of 21.9 (15), 16.9 (11) and 19.9 (15) days, respectively, but the difference was not statistically significant (P=0.09). Although the three antibiotic regimens investigated appear equally effective, benzathine penicillin offers the convenience of a single, intramuscular injection instead of the 10 days of therapy needed with the other two drugs.     

Branhamella catarrhalis pneumonia in patients with immunoglobulin abnormalities

The importance of Branhamella catarrhalis pneumonia has only recently been appreciated. Predisposing underlying illness associated with this organism have not yet been clarified. We report five cases of Branhamella catarrhalis pneumonia occurring in patients with diseases associated with documented quantitative immunoglobulin deficiencies. Normal immunoglobulins appear to be important host defense mechanisms in preventing infection with this organism.