Vitamin A in acne vulgaris.
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Biomedical subjects
Publications and source records attributed to R Walker.
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Carboplatin, a cisplatin analogue, was administered as an intravenous (IV) one-hour infusion in a 4-consecutive weekly dose schedule to 44 patients with recurrent childhood brain tumors. Twenty-four patients were registered on our phase I, and 20 on our phase II studies. The maximum tolerable dose derived from our phase I study was 210 mg/m2/wk in patients with solid tumors, and the recommended dose for subsequent pediatric phase II studies was 175 mg/m2/wk. This dose was administered to 14 patients in the phase I and all 20 patients in the phase II study. Nine of 36 (25%) evaluable patients in the combined studies experienced objective responses for a median duration of 10+ months. Seven of nine responders had received prior cisplatin. Disease-specific response rates were as follows: medulloblastoma, six of 14 (43%) with three complete (CR) and three partial responses (PR); pineoblastoma, one of one (PR); germinoma, one of two (CR); and brainstem glioma, one of eight (13%) (PR). Carboplatin had mild emetic effects but no significant auditory or renal toxicity. Thrombocytopenia (less than 49,000) was encountered in nine of 28 (32%) evaluable trials at a dose of 175 mg/m2/wk. Because of its low potential for auditory, renal, and emetic toxicity, ease of administration, and high disease-specific activity, carboplatin deserves further study in multiagent phase II and III trials, especially in chemotherapy-sensitive diseases such as medulloblastoma.
A cohort of BB/E rats derived from litters with a high and low incidence of IDDM was studied prospectively to examine the relationship between circulating autoantibodies, islet insulin secretion, pancreatic infiltration, and islet cell replication during the pre-diabetic period. Although a higher incidence of islet cell surface (ICSA) and insulin autoantibodies (IAA) was detected in the diabetes-prone than in the low diabetic-incidence BB/E rats there was no correlation between the two antibodies in individual animals. Moreover, ICSA, but not IAA, were associated with loss of first phase islet insulin release. Between 75 and 105 days of age the number of diabetes-prone rats with ICSA and impaired islet insulin secretory function increased. Over the same period, there was a concomitant increase in the proportion of diabetes-prone animals with pancreatic infiltration, and increased islet endocrine cell proliferation. All these interrelated phenomena were observed in diabetes-prone BB/E rats at a time when the animals were normoglycaemic.
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We developed a simplified approach to the setting up of a radiology quality-assurance program based on the standards of the Joint Commission on Accreditation of Hospitals. This approach gives priority to the little-discussed issues that have maximum impact on patient care: the monitoring of the radiologic service as a whole and personnel performance. Quality control of equipment and radiation protection have been extensively dealt with in the literature and are omitted.
The presence of insulin autoantibodies (IAA) and islet cell surface antibodies (ICSA) was sought in two longitudinal studies, involving BB/Edinburgh rats of high (BB/E/H, n = 157) and low (BB/E/L, n = 61) susceptibility to diabetes development. Both studies were designed to correlate pancreatic morphology with cellular and humoral immunity. In Study I, groups of eight male and eight female non-diabetic rats of the BB/E/H line were killed at 15 day intervals from 30-105 days and plasma samples were obtained by cardiac puncture. In study II, 61 BB/E/H and 41 BB/E/L rats underwent pancreatic biopsy 1-3 times from 30 days of age until onset of diabetes or 150 days, plasma samples being taken from the tail vein at biopsy. Both studies revealed a higher prevalence for ICSA than IAA in BB/E rats. Whereas a highly significant association of ICSA with diabetes development was observed in study II (chi 2 = 8.30, P less than 0.005), IAA were associated with diabetes development only weakly (P less than 0.03, Mann-Witney U-rank test). No correlation between the presence of ICSA and IAA in individual rats was observed and IAA were not significantly associated with BB/E/H in preference to BB/E/L rats, although positive IAA values were significantly elevated in the former compared with the latter (P less than 0.01). These observations support the concept that IAA form part of a background of heightened autoimmunity against which frank diabetes develops in some animals.
Several immunological responses of the spontaneously diabetic BB rat colony in Edinburgh designated (BB/E) have been studied. The proliferative responses to Con A and LPS, ability to make IL-2 and to show NK activity have been studied using diabetic and non-diabetic BB/E rats and normal Wistar rats. Our data suggest that the diabetic animals in the BB/E colony do not have marked deficiencies in any of these parameters. Lymphopenia and depressed T-cell responses do not appear to be a prerequisite for the development of diabetes in the BB/E colony.
General practice training schemes currently have no structured methods of assessment and most rely on a variety of subjective ratings of performance. In West Cumbria the ;objective structured clinical examination' has been used to assess training performance in areas covered by small group teaching during the preceding terms. Consultation skills, interpretation of clinical data and a number of aspects of practice management were tested. The examination was conducted in the local postgraduate centre and assessed 20 trainees. Each trainee received feedback of his performance on each problem set and also an overall comparison with his peers.This method of assessment appeared to be well received by trainees and was practicable within the limited resources available. In addition, the variety of problems set allowed for a broad range of trainees' performances to be assessed.
An improved method for the isolation of a double-strand-specific RNase from snake venom is presented. This RNase, called CSV, was used to cleave yeast tRNAPhe and tRNA2Glu and tRNAfMet from Escherichia coli. In addition these RNAs and E. coli tRNAPhe were examined with the single-strand-specific nuclease S1. The results are discussed in terms of the specificity of CSV RNase and the structure of tRNAs. S1 nuclease digestions at increasing temperatures allowed the melting of tertiary and secondary structure to be monitored. 5S rRNA from E. coli, Thermoplasma acidophilum and the chloroplasts of Spinacia oleracea were digested with CSV and S1. The information these results give on the secondary-structural differences between different classes of 5S rRNA are discussed. Supporting evidence is found for tertiary interactions between hairpin loop c and internal loop d of eubacterial 5S rRNA.
The ability of recombinant Interferon-gamma to induce class II expression in vitro on pancreatic islet B cells has been investigated by exposing islets isolated from BB/E and normal Wistar rats to Interferon-gamma and then staining successively with monoclonal antibodies specific for rat class II MHC antigens and insulin. Induction of class II expression was never observed on islet cells obtained from either normal Wistar rats or rats from the BB/E low diabetes incidence (less than 2%) subline. In contrast, pancreatic B cells from rats from the BB/E high diabetes incidence (60-70%) subline expressed class II antigen following culture with Interferon-gamma.
Concentrations of cortisol in saliva and plasma were compared in matched samples during a standard 1 mg dexamethasone suppression test. The study involved 185 routine psychiatric admissions, all of whom were classified according to DSM-III criteria. In a group of 122 matched samples of saliva and plasma, there was a Pearson correlation coefficient of 0.867 and a Spearman rank correlation coefficient of 0.869. Medication with anticholinergic side effects had little effect on the correlation and was not associated with major difficulties in salivary sampling due to "dry mouth." In a group of 178 diagnoses where both saliva and plasma were obtained, results were almost identical. Although nonsuppression was found in all psychiatric conditions, there was a very significant association with major depressive episode with melancholia.
The reduction of nitrate in germ-free, gnotobiotic and conventional rats was investigated using blood methaemoglobin values as indicative of nitrite formation. Nitrate reduction was found to occur in the absence of a microbial flora, and throughout the experiment the blood content of methaemoglobin was higher in germ-free than in conventional rats. In vitro incubations of the gastric and small-intestinal mucosae of germ-free rats confirmed the presence of a heat-labile nitrate-reducing system. Measurement of the gastro-intestinal pH of germ-free and conventional rats revealed a generally higher pH value throughout the germ-free gastro-intestinal tract, with highly significant differences in the luminal pH of the forestomach, jejunum/ileum and caecum and a significant difference in the pH of the glandular stomach. Although some formation of N-nitrosoproline from proline and nitrate occurred in germ-free and gnotobiotic rats, nitrosation proceeded more readily in conventional rats. This effect may have been due to the lower gastric pH in the conventional rats although a more direct role for the flora cannot be discounted.
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Significant numbers of mast cells have been demonstrated histologically around the periphery of the invasive rat mammary adenocarcinoma 13672NF. The number of mast cells at microfoci along the tumour:host tissue junction was significantly greater than that found in normal mammary tissues, and few mast cells were detected within the tumour itself. Mast cell degranulation, often associated with disruption and lysis of the connective tissue matrix, was a common feature in later stages of tumour proliferation. When soluble products derived from purified rat peritoneal mast cells were added to monolayer cultures of rat stromal fibroblasts or tumour cells they stimulated a significant increase in total collagenase production, and the mast cell products were also capable of activating the latent collagenases thus produced. Histological examination indicated that degradation of local collagenous matrix was a common feature of mast cell degranulation, an observation possibly explained by the release of mast cell enzymes and/or the potential of this cell to modulate the expression of collagenolytic activity by surrounding cells. These observations suggest that, at least in some tumours, mast cells contribute to the connective tissue breakdown commonly associated with tumour invasiveness and metastatic spread.
In accordance with previous studies the bioactivation of 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) to mutagens in the Ames test was preferentially catalysed by the 3-methyl-cholanthrene-induced cytochromes P-448, in contrast to the phenobarbital-induced forms of the cytochrome. The mutagenicity of IQ catalysed by microsomes, in the absence of cytosol, was much lower when compared with that observed with S9 fractions. Cytosol itself could not activate IQ but markedly potentiated the microsome-mediated mutagenicity of the carcinogen. The effect of the cytosol was still evident when microsomal metabolism was terminated, indicating that the cytosol contains enzyme(s) that can further convert the microsome-generated metabolites of IQ to more potent mutagens. The cytosolic enzyme(s) were inducible by pre-treatment of the rats with Aroclor 1254. The higher efficiency of activation of IQ to mutagens by Sprague-Dawley S9 mixes when compared with similar preparations from the Wistar rat could be attributed not only to differences in the rate of microsomal metabolism but also to the higher ability of the Sprague-Dawley cytosolic fraction in further metabolizing the microsome-generated metabolite(s). The present study demonstrates clearly that the mutagenic response of this compound in the Ames test may be profoundly modulated by the cytosolic fraction and its role in the metabolic activation of pre-mutagens merits further investigation.
51.4% of 1,954 grain elevator workers surveyed in 1978 and 1979 complained of pruritus following exposure to grain dusts. 95% of 796 grain elevator workers surveyed in 1985 noted that pruritus following exposure to grain dust was of short duration. Exposure to barley dust and oat dust provoked the greatest number of complaints. Those with a past history of infantile eczema were significantly more likely to complain. Younger workers were more likely to complain than older workers. 13.1% of those surveyed in 1985 complained of a rash following exposure, in 35% of whom it lasted more than 1 day. Nasal congestion, ocular and oropharyngeal irritation were also frequent complaints.
The purpose of this investigation was to determine if a new proposed arm ergometer protocol was advantageous in eliciting higher peak oxygen uptake (peak VO2) when compared with two protocols currently referred to in the literature. Ten male subjects were tested on three different exercise protocols; a discontinuous test (DT), a continuous test (CT) and a new proposed jump-max test (JMT). The CT began at a work rate of 33 watts (W) (40 rpm) with the power output (PO) being increased 16 W every 3 minutes. The DT began without resistance on the ergometer flywheel (50 rpm) and the work rate was increased by 25 W every 3 minutes with a 1-minute rest between stages. The JMT began with a 3-minute pretest to determine a PO which elicited a HR of 120 +/- 5 beat min-1. After a 2-minute rest, subjects began exercise at the predetermined work rate (80 rpm) with the PO being increased 20 W each minute of the test. Oxygen uptake was measured minute by minute via open circuit spirometry. Peak VO2 was higher (p less than 0.05) in the JMT (mean +/- SEM = 2.36 +/- 0.06 l.min-1) when compared with either (means +/- SEM = 2.16 +/- 0.07 l.min-1) or the CT (means +/- SEM = 2.04 +/- 0.10 l.min-1). No difference (p greater than 0.05) existed in peak VO2 between the CT and the DT. These data suggest that the proposed JMT may result in a higher measured peak VO2 in subjects when compared with either DT or CT of moderate to long duration.