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Biomedical subjects

T H Brown

Publications and source records attributed to T H Brown.

90 records · Page 5Linked to original sources

Giant synaptic potential hypothesis for epileptiform activity.

According to one hypothesis, the paroxysmal depolarizing shift observed in the penicillin model of epilepsy results from a giant excitatory postsynaptic potential. This hypothesis has recently been questioned, primarily because it has never been subjected to rigorous experimental examination. Four quantitative predictions were derived from this hypothesis and tested in CA3 pyramidal neurons of the hippocampus. The four critical predictions concern the behavior of the paroxysmal depolarizing shift under current- and voltage-clamp conditions as a function of membrane potential. The experiments confirmed all four predictions.

Action Potentials↗

Direct effects of neostigmine on aneural myotube cultures.

Long term (24--96 h) treatment of a mouse-derived myogenic cell line (G8) with meostigmine or physostigmine markedly reduces binding of alpha-bungarotoxin (alpha-BuTx) to these cells. Protein synthesis in these cultures is markedly reduced and cell morphology degenerates. Myotubes maintain slightly hyperpolarised resting membrane potentials, and are able to respond to iontophoretic acetylcholine (ACh) application with overshooting action potentials. Prolonged exposure to neostigmine also inhibits protein synthesis in a fibroblastic cell line (B82). The results suggest that degenerative changes at the neuromuscular junction associated with chronic neostigmine treatment in vivo are due to a direct action of the anticholinesterase on the muscle, rather than to altered intracleft ACh levels [2] or to presynaptic effects of the anticholinesterase [15].

Animals↗

Regulation of acetylcholine receptor levels by a cholinergic agonist in mouse muscle cell cultures.

The effects of continuous exposure to carbamylcholine (CbCho) on regulation and stabilization of acetylcholine receptors (AcChoR) were studied in cell cultures of G8, a continuous mouse muscle cell line. Exposure of cultures to 10-100 muM CbCho for 24-48 hr produced a 30-50% reduction in (125)I-labeled alpha-bungarotoxin binding. CbCho was not found to alter cell morphology, protein metabolism, or amino acid incorporation. Electrophysiological experiments demonstrated a 75% reduction in the maximum sensitivity of the myotubes to iontophoretic application of acetylcholine (AcCho). The reduction in AcCho sensitivity appeared to represent a true loss of functional receptors because there were no changes in the passive electrical properties of the cells or in the AcCho reversal potential and because receptor desensitization appeared not to be involved. Tetrodotoxin had no effect on receptor levels, either alone or in combination with CbCho. Receptor degradation in control cells could be described kinetically as a first-order process with a half-time of 19.2 hr; turnover rate in receptors remaining after prolonged exposure to CbCho was indistinguishable from that in control cells. We conclude that a receptor-active ligand can exert negative control over AcChoR levels and that prolonged exposure to an AcCho analog is not sufficient to induce a stable population of receptors in these cells.

Acetylcholine↗

Evoked neurotransmitter release: statistical effects of nonuniformity and nonstationarity.

Recent studies of the mechanism of quantal neurotransmitter release have assumed that the number of quanta released at each stimulation is binomially distributed and have sought to estimate the binomial parameters n and p. Mathematical analysis and computer simulations show that temporal variation in the number of eligible or filled release sites and either spatial or temporal variation in the probability of release at a site can drastically bias such estimates, while the experimental histograms remain statistically indistinguishable from those predicted by the binomial law. Interpretation of the estimates n and p in terms of ultrastructural or physiological characteristics of the nerve terminal is liable to significant error if departures from the binomial assumptions are not suitably assessed.

Computers↗

24-hour intragastric pH measurement in the assessment of duodenogastric reflux.

In this study we compared the results of measurement of duodenogastric reflux using 24-hour intragastric pH monitoring and nasogastric aspiration with analysis of bile acid and alpha amylase concentrations. Eight patients were studied at least 5 months after biliary and/or gastric surgery. The correlation coefficient of pH and bile acid concentration was 0.36 (p less than 0.001) and of pH and amylase concentration was 0.48 (p less than 0.001). If a pH greater than 4.0 was taken to indicate duodenogastric reflux this had a sensitivity of 84% compared with either high bile acid or amylase concentration. Bile acid concentration has been the "standard" method of measuring duodenogastric reflux. pH monitoring is relatively simple to perform, causes little patient distress, and can measure episodes of duodenogastric reflux over a continuous 24-hour period.

Bile Acids and Salts↗

Acute gastritis occurring within 24 hours of severe head injury.

The purpose of this study was to evaluate the early appearance and incidence of stress gastritis following severe head injury. We performed upper esophagogastroduodenoscopy in 44 patients within 24 hours of a head injury. All patients were comatose and required ventilatory support. Forty of the patients (91%) had gastritis at esophagogastroduodenoscopy. The lesions were distributed in the fundus and corpus of the stomach (77% of the patients), in the esophagus (30% of the patients), in the antrum (25% of the patients), and in the duodenum (7% of the patients). The grade of gastritis at esophagogastroduodenoscopy did not correlate with the severity of the head injury, the type of head injury sustained, the timing of esophagogastroduodenoscopy after head injury, or the presence of shock on admission. However, patients with grade III gastritis had a greater injury Severity Score than patients with grade 0 gastritis (normal mucosa). Gastroduodenal mucosal damage is common after severe head injury and occurs soon after the event.

Acute Disease↗

Icotidine, an antagonist of histamine at both H1 and H2 receptors.

SK&F 93319 (icotidine), 2-[4-(3-methoxypyrid-2-yl)butylamino]-5-[(6-methylpyrid-3-yl )-methyl]- pyrimidin-4-one trihydrochloride, has been identified as a novel agent which combines into one molecule the ability to antagonize the actions of histamine at H1 and H2 receptors across a similar concentration or dose range. The degree of antagonism of vascular responses to histamine exceeds that possible with either an H1- or H2-receptor histamine antagonist alone. SK&F 93319 may have therapeutic utility in conditions requiring simultaneous antagonism of histamine at H1 and H2 receptors.

Animals↗

Umbilical hernia in adults: day case local anaesthetic repair.

INTRODUCTION: The waiting times for elective surgery of Umbilical hernia (UH) in adults are unacceptably long in some cases. During this period, irreducibility and strangulation are possible. We operate on adult patients under local anaesthesia (LA) as day cases to avoid this delay and describe our experience in this paper. AIMS: The aims of our study were to look at the age and sex distribution, body weight, type and amount of local anaesthetic used, morbidity, admission and readmission rates, and waiting times of adult patients operated on for UH under LA. MATERIALS AND METHODS: It was a retrospective study covering a 4 year period from July 1996 to June 2000 including all adult patients undergoing the above procedure under the care of a single consultant general surgeon. A standard Mayo repair using non absorbable material was used without a mesh or a drain. RESULTS: 32 patients with UH were operated on under LA, 23 males and 9 females with a median age of 51 years (range 20 to 86 years). The body weight ranged from 63 to 120 (median 87) kg. The average duration of the procedure was 30 (range 22-40) minutes. Sedation was needed in 4 patients. Two patients developed wound infections, one superficial and one deep. There was no mortality. The median period of follow-up was 24 (range 4-48) months and there was no recurrence. The median waiting time for the operation was 6 weeks. CONCLUSIONS: Day case local anaesthetic repair of UH in adults seems to be safe and feasible with an acceptable morbidity. Suture repair in the right patient has excellent results and the waiting times are acceptable.

Adult↗