Safety, tolerability, efficacy and plasma concentrations of diethylcarbamazine and albendazole co-administration in a field study in an area endemic for lymphatic filariasis in India

Filariasis control programmes are moving towards a strategy of repeated single-dose mass treatment of endemic populations. Using a combination, such as albendazole (ALB) to diethylcarbamazine (DEC) gives both macrofilaricidal and anti-helmintic activity. However, the safety of the combination versus DEC alone should be established in field studies in large populations prior to incorporation into national programmes. The present study compared the safety, tolerability, and efficacy of single doses of DEC 6 mg/kg + ALB placebo with DEC 6 mg/kg + ALB 400 mg in populations living in two filariasis endemic villages in the district of Wardha in western India. The study was double blind, parallel group, and randomized. Safety and tolerability study were studied in males and females older than 5 years. Safety was assessed by monitoring if adverse events (AEs) over 5 days affected daily acivities. Subjects in the 2 treatment groups experienced insignificantly different effects on daily activities and the combination was shown to be safe. Efficacy was evaluated by microfilaraemia (Mf), immunochromatographic test (ICT) and ultrasonography (USG) at 0, 3, 6, and 12 months of follow up. The efficacy study enrolled 103 male patients (aged 18-50 years) in microfilariae positive, clinical disease and asymptomatic, amicrofilaremic groups. There was no significant difference in efficacy between groups at 12 months. Within the Mf positive group, significant differences were seen in microfilaraemia (P < 0.001) with both treatments, and in USG (P < 0.001 and P < 0.004 respectively), at 12 months. The present field study has shown the combination of DEC + ALB to be as safe as the single drug DEC and thus the combination can be put in use in the national filariasis control programmes. Both drugs were adequately absorbed. The study at present does not provide evidence for the greater efficacy of the combination at 12 months follow up. While the safety of the combination has been ascertained, the incorporation or otherwise of ALB into national programmes for greater efficacy must await results of studies with longer follow up.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Controlled trial of continuous inflating pressure for hyaline membrane disease

A controlled trial of elective intervention with continuous inflating pressure (CIP) was performed in infants with severe hyaline membrane disease who weighed more than 1000 g at birth. Infants entered the trial if their arterial oxygen tension (PaO2) fell below 60 mmHg while breathing a fractional inspired oxygen concentration (F1O2) greater than 0-95. 11 out of 12 infants in the CIP-treated group and 10 out of 12 in the control group survived. 7 treated and 6 control infants required mechanical ventilation. When CIP was started the Pao2 of the treated infants increased, and they breathed high concentrations of oxygen for a significantly shorter period than the control infants. During the 31-month duration of the trial 107 other infants with severe hyaline membrane disease were admitted who did not meet the criteria for entry to the trial. 37 survived after breathing high concentrations of oxygen (F1O2 greater than 0-60) spontaneously without any ventilatory assistance, and the remaining 70 infants were already being ventilated on their arrival in the unit, usually because they had required mechanical ventilation during transfer from other hospitals. The neonatal survival rate for those infants born in this hospital during the study period was 88% (50 out of 57 infants) and for those referred from other hospitals it was 69% (51 out of 74 infants). The maximum further increase in overall survival rate that might have been achieved in our population of infants if CIP had been initiated very early in the course of the illness was 5%--i.e. from 77% (101/131) to 82% (107/131).     

Endoscopic retrograde cholangiopancreatography in children

Gastroduodenoscopy and retrograde cholangiopancreatography has been performed on 25 occasions in 20 children aged between 7 and 16. Radiographs of the clinically relevant duct or ducts were achieved in 96% of attempts, with no complications. The diagnostic information proved useful clinically; in particular it provided a precise map if biliary or pancreatic surgery was being contemplated. Several unexpected congenital duct anomalies were found. This and other recent reports, particularly from Germany, indicate that endoscopic retrograde cholangiopancreatography deserves greater application in children, and can also be used in babies.     

Differential diagnosis of corneal oedema assisted by in vivo confocal microscopy

The purpose of this study was to demonstrate microstructural differences between clinically similar, but aetiologically different, cases of corneal oedema in four subjects. In vivo confocal microscopy highlighted oedema of the basal epithelium, prominent nerve–keratocyte interactions, and typical ‘epithelialization’ of the endothelium in a case of iridocorneal endothelial syndrome; however, a similar microstructural appearance was observed in a case of presumed herpetic disciform keratitis. The latter diagnosis was subsequently revised on this basis. Confocal examination of Fuchs’ endothelial dystrophy demonstrated oedema of the basal epithelium, prominent wing cells, anterior stromal alterations, fibrosis of Descemet’s membrane and a typical ‘strawberry’ appearance of the endothelium. In contrast, in vivo microstructural examination of bilateral keratoconus with hydrops confirmed oedema mainly involving the epithelium and anterior stroma. In vivo confocal microscopy allows the clinician to observe the living cornea at a microstructural level and to better diagnose and differentiate borderline or unusual cases of corneal oedema.     

Digital beam attenuator technique for compensated chest radiography

The feasibility of producing patient-specific beam attenuators for chest radiography has been investigated using an anthropomorphic phantom and a human volunteer. A low-dose test exposure is digitized, processed, and used to print a small cerium filter, which is placed in the x-ray beam near the collimator. The final radiograph is recorded on film. The technique results in relatively uniform film exposure, so that structures in all regions of the chest are simultaneously displayed with optimal film contrast. The equalized exposure improves image quality in the normally underpenetrated regions and reduces the role of cross-scatter from the lungs. The image is analogous to optical or computer-processed unsharp masking techniques, but the processing is accomplished in the x-ray beam and results in an improved exposure distribution, giving advantages that cannot be achieved with image processing techniques alone.     

In vivo confocal microscopy of climatic droplet keratopathy

We describe the corneal microstructural changes in a patient with spheroidal degeneration using in vivo confocal microscopy. Multiple hypo‐ and hyper‐reflective spherical lesions were observed in the anterior corneal stroma and Bowman's layer ranging from 45 to 220 μm in size. The corneal epithelium, posterior stroma and endothelium were otherwise unaffected. In vivo confocal microscopy demonstrates good correlation with excised histological samples in climatic droplet keratopathy. It provides a non‐invasive technique to examine the living cornea for degenerative disease and acts as a bridge between clinical and laboratory observations.