The influence of food on the pharmacokinetics of ''biphasic'' nifedipine at steady state in normal subjects.

Previous studies following single dose administration have suggested that the pharmacokinetics of various nifedipine formulations could be influenced by the timing of associated food consumption. In order more closely to reflect the clinical situation we have carried out a study at steady state using a 'biphasic' formulation comprising 'rapid' and 'retarded' drug release components. Fifteen normal subjects took 20 mg 'biphasic' nifedipine 12 hourly for 10 days. Studies were carried out on days 4, 7 and 10. On these days the nifedipine was taken 2 h or 1 h before or immediately following a light breakfast. A light breakfast influenced neither the rate nor the extent of nifedipine absorption nor the rate or extent of major metabolite appearance. We conclude that at steady state the timing of a light meal is unlikely to alter in any clinically important manner the pharmacokinetics of nifedipine released from 'biphasic' tablets.     

National intercomparisons of I radioactivity measurements in nuclear medicine centres in India

National intercomparisons of activity measurements of ¹³¹I, a radioisotope widely used for diagnosis and therapy of thyroid related ailments, were initiated in 1979 as a quality assurance program, towards improving radiation safety procedures and related dosimetry in Nuclear Medicine Centres (NMCs) in India. Oral administration of a known quantity of radioiodine to patients requires accurate radioactivity measurements to be performed on a well-calibrated isotope calibrators. Under or over estimation of the activity due to a faulty or uncalibrated isotope calibrator could provide misleading results. Calibration of isotope calibrators and the traceablity of subsequent measurements to the national standards laboratory is one of the essential basic radiation safety requirement of the IAEA. In view of the stringent quality assurance requirements for activity measurements imposed by Atomic Energy Regulatory Board, a National Intercomparison Program was initiated and to date ten such intercomparison programs have been conducted by the Radiation Safety Systems Division, of the Bhabha Atomic Research Centre. This program has benefited the participants by making their measurements traceable to the National Primary Standards. Over the years there has been a marked increase in the number of NMCs participating in the intercomparison programs. As a result, the number of institution showing large deviation from the correct value has decreased considerably over the years. This program thus, has enabled participating NMCs to check their isotope calibrators so as to ensure proper delivery of radiation dose to the patients and hence to optimise patient exposure.     

Information seeking and interactive videodisc preparation for third molar extraction.

Patient response to interactive videodisc preparation for third molar extraction surgery was examined as a function of self-reported information-seeking style. Amount learned was compared among patients informed via an interactive videodisc, noninteractive videotape of the same material, or surgeon only. Anxiety levels and satisfaction with preparation were compared between the videodisc and videotape groups. At consultation, patients (n = 35) were randomly assigned to either the disc- or the tape-viewing group. First, subjects completed a demographic survey, state anxiety scale, quiz on knowledge about third molars and surgery risks and complications, and information-seeking scales. Immediately after viewing the video, subjects completed another anxiety scale and a multiple-choice quiz covering the material presented. Subsequently, another 25 patients undergoing the routine (surgeon-only) consultation procedure were given the same multiple-choice quiz following consultation. Quiz scores differed significantly among the groups; mean percent correct for the tape-viewing subjects was 85; for disc-viewing subjects 72.6; for surgeon-only subjects, 40. Self-rated information seeking was unrelated to amount of video viewed by disc subjects (on average, 64% of the videodisc was viewed), and disc subjects who rated themselves higher in information-seeking achieved the lowest postpreparation quiz scores. Subjects in the disc group were significantly more satisfied with the amount of preparation than the tape group. Although disc group subjects were significantly less knowledgeable following consultation than were tape group subjects, interactive videodisc preparation for third molar extraction appears to have some advantages over more traditional approaches. Further research is needed to determine whether this approach to preparing patients is suitable for widespread clinical use.     

Non-familial juvenile polyposis with histological evidence of adenomatous transformation.

A 14-year-old male presented with abdominal pain, diarrhoea and a sensation of something prolapsing through the anus during defecation, and was found to have diffuse colonic polyposis. There was no evidence of mucocutaneous hyperpigmentation and family history was negative, suggesting a diagnosis of non-familial juvenile polyposis. Histological analysis of multiple endoscopic biopsies showed features typical of juvenile or retention type (hamartomatous) lesions: dilated cystic glands lined by mucocus-secreting epithelium and prominent, inflamed and congested lamina propria. However, admixed with these features, focal areas of atypical adenomatous changes were recognized. Even the intervening normal-looking colonic mucosa showed some dysplastic changes. These findings indicate that hamartomatous and atypical adenomatous epithelial changes can co exist in non-familial juvenile polyposis and the latter may confer a risk of malignant transformation in this otherwise non-neoplastic disease.     

Evaluation of peptone glucose fluconazole agar as a selective medium for rapid and enhanced isolation of Aspergillus fumigatus from the respiratory tract of bronchopulmonary aspergillosis patients colonized by Candida albicans.

We have reported earlier that Aspergillus fumigatus is inhibited in vitro by Candida albicans which also interferes in its isolation from sputum experimentally seeded with predetermined graded inocula of the two fungi. It was further shown that this interference was neutralized by employing peptone glucose agar with incorporation of fluconazole which is more inhibitory to C. albicans than to A. fumigatus. This communication embodies the results of evaluation of peptone glucose fluconazole agar (PGFA) as a selective culture medium for rapid and enhanced isolation of A. fumigatus from sputum of patients clinically suspected of aspergillosis with C. albicans colonization in the respiratory tract. Of the 23 sputum specimens and one broncho-alveolar lavage collected from 15 suspected aspergillosis patients, A. fumigatus was isolated from all (100%) on PGFA as against only 19 specimens (79%) that proved to be positive on the control PGA medium (P<0.05). The greater efficacy of PGFA than that of PGA was further evident from the 2-fold higher A. fumigatus mean colony count (8.2+/-1.87) on the former medium than on the latter (3.7+/-1.00), and this difference was found to be statistically significant (P<0.05). Besides, A. fumigatus colonies were macroscopically recognizable within 2-3 days on PGFA at 28 degrees C in strong contrast to 5-7 days required on PGA. Based upon these observations, PGFA is recommended for wider application as a selective medium for rapid and enhanced recovery of A. fumigatus from sputum of patients clinically suspected of aspergillosis with C. albicans colonization in their respiratory tract.     

Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.

BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.