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Biomedical subjects

W E Thomas

Publications and source records attributed to W E Thomas.

At least 73 records · Page 4Linked to original sources

Choline uptake by glomerular synapses isolated from bovine cerebellar vermis.

[3H]Choline uptake was investigated in a highly enriched preparation of glomerular particles isolated from bovine cerebellar vermis. Kinetic analysis indicates that a high-affinity choline uptake system with a relatively low maximum uptake velocity is present. At a substrate concentration of 10(-7) M, [3H]choline uptake was shown to be sodium-dependent, hemicholinium-sensitive and non-reactive to increasing concentrations of unlabeled choline. These findings support the presence of a high-affinity choline uptake system in cerebellar glomeruli and would seem to be consistent with the suggestion that a small proportion of mossy fibers are cholinergic in this brain region.

Animals↗

Studies of neurotransmitter chemistry of central nervous system neurons in primary tissue culture.

Primary tissue culture methods have been applied to various areas of the central nervous system, including cerebral cortex, spinal cord, cerebellum, hippocampus, hypothalamus, striatum, mesencephalon, lower brain stem and retina. Experimental studies in vitro involving central neurotransmission are discussed here. Information gleaned from such studies impacts on neurotransmitter identification, neuronal development, patterns of receptor distribution, peptidergic transmission, transmitter metabolism, synaptogenesis and the regulation of synaptic development.

Acetylcholine↗

Intragastric bile acids and scintigraphy in the assessment of duodenogastric reflux.

Following endoscopic gastric juice aspiration, intragastric bile acids were measured in 105 patients undergoing routine or review gastroscopy. Subsequently, duodenogastric reflux was assessed using 99mTc butyliminodiacetic acid (BIDA) scintigraphy and intragastric bile acid levels compared with the grades of reflux assessed scintigraphically. There was a significant correlation between both free and total intragastric bile acid levels and the degree of radiological bile reflux, especially when reflux was severe. Both endoscopic measurements of bile acids and BIDA scintigraphy appear to be useful methods for determining duodenogastric reflux, but neither may be accurate enough to quantify minor degrees of reflux.

Bile Acids and Salts↗

Intragastric bile acids and histological changes in gastric mucosa.

Multiple gastric biopsies and gastric juice aspirates were taken in 108 patients undergoing routine or review gastroscopy for a variety of upper gastrointestinal disorders. The gastric juice was measured for free and total bile acids and the biopsies examined for premalignant mucosal changes. Total bile acid levels were significantly higher in patients with atrophic gastritis, intestinal metaplasia and dysplasia but not chronic gastritis. There was no correlation between the severity of the dysplasia and total bile acid levels. Free bile acid levels were significantly higher in patients with atrophic gastritis but not in patients with chronic gastritis, intestinal metaplasia or dysplasia. These results suggest that intragastric bile acids may be implicated in premalignant histological changes of gastric mucosa and thus play a part in gastric carcinogenesis.

Atrophy↗

Impaired spermatogenesis in testes at risk of torsion.

The oligospermia observed after unilateral torsion of the spermatic cord could reflect immunological damage to the opposite testis. An alternative explanation, that there may be a pre-existing defect in spermatogenesis, was tested in 20 post-pubertal males with acute torsion. In a prospective study the contralateral testis was biopsied at operation and the histological appearances were related to subsequent testicular function as assessed by seminal analysis 3 months later. Thirteen patients had biopsy evidence of partial maturation arrest in spermatogenesis which was either mild (6), moderate (4) or severe (3), and ten of these were oligospermic (less than 20 X 10(6)/ml). By contrast all seven patients with normal histology had a sperm concentration greater than 25 X 10(6)/ml. Histological grading of spermatogenesis by the Johnsen technique gave a higher score in patients with a normal biopsy (median 9.01, semi-quartile range 8.96-9.21) than in those with abnormal histology (median 8.28, semi-quartile range 7.98-8.45, P less than 0.001) and correlated with the log of the sperm concentration 3 months later (r = 0.79, P less than 0.001). There was minimal anti-sperm and no anti-testis antibody formation following torsion. Serum FSH levels were raised in 6 of 10 oligospermic patients, while all those with a normal sperm count had FSH concentrations within the normal range. Thus many patients who develop testicular torsion have an underlying defect in spermatogenesis, which correlates closely with poor postoperative exocrine function.

Adult↗

Secondary aorto-enteric fistulae: towards a more conservative approach.

Eight cases of secondary aorto-enteric fistulae are presented occurring 9 months to 10 years after aortic Dacron grafting. In four patients there was a simple fistula between the anastomosis and the adherent duodenum, three patients had clinically infected grafts and one had a false aneurysm that had ruptured into the bowel. The four patients with a simple fistula had direct suture repair of the defect. One developed a recurrent fistula at 2 months and was successfully repaired again by direct suture. All four patients remain well at a follow-up of 1-5 years. The other four patients had the grafts excised, with local regrafting in two cases, both patients remaining well at follow-up. One patient had an axillo-bifemoral graft, but died at 30 days of overwhelming sepsis. The final patient, a girl with diffuse aneurysmal disease, had the aortic stump oversewn but no reconstruction. She died at 9 months of aortic stump disruption. These results suggest that a more conservative approach to the operative correction of secondary fistulae should be used wherever possible.

Adolescent↗

Homeopathy.

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Dose-Response Relationship, Drug↗

Morphology of acetylcholinesterase-containing neurons in primary cultures of dissociated rat cerebral cortex.

Acetylcholinesterase-containing neurons were investigated in primary cultures of cerebral cortex. Neuronal cholinesterase staining was essentially totally attributable to acetylcholinesterase based on its pattern of sensitivity to pharmacological inhibitors. The mean percentage of stained neurons in the cultures was 2.17. Stained neurons of all morphologies were detected: however, the majority of the cells possessed bipolar morphology. The stained bipolar neurons were not a homogeneous morphological population.

Acetylcholinesterase↗

Organophosphate-mediated inhibition of choline acetyltransferase activity in rat brain tissue.

Administration of the organophosphate compound soman in rats resulted in an inhibition of choline acetyltransferase activity in almost all brain regions examined. Enzyme activity was inhibited by 20-50% in various brain regions 30 min after soman injection (94-120 micrograms/kg). Enzyme activity in two regions decreased with time to a near zero level by 3 h after injection.

Animals↗

Synthesis of acetylcholine and gamma-aminobutyric acid by dissociated cerebral cortical cells in vitro.

Biosynthesis of acetylcholine and gamma-aminobutyric acid was investigated in primary cultures derived from embryonic rat cerebral cortex. The cortical cultures contained a mixture of neurons and non-neuronal cells. Cortical neurons were viable for at least 2 months in vitro. The cultures accumulated [3H]choline from the medium and synthesized acetylcholine. Choline uptake was significantly reduced by hemicholinium-3 and acetylcholine synthesis by intact cultures was partially inhibited by naphthylvinylpyridine. In lysed cultures, greater than 90% of acetylcholine synthesizing activity was inhibited by naphthylvinylpyridine. Acetylcholine synthesis and storage by intact cells increased as the concentration of choline increased and approached saturation near 50 microM choline. Also, the synthesis and storage of gamma-aminobutyric acid from [3H]glutamate increased as the concentration of glutamic acid increased and began to saturate near 25 microM glutamate. The rates of synthesis of acetylcholine from 5 microM choline and of gamma-aminobutyric acid from 50 microM glutamate were linear for at least 30 min. The synthesis and accumulation of acetylcholine and gamma-aminobutyric acid from their respective precursors showed a similar dependence on culture age; they increased constantly during the first 3 weeks in culture, thereafter they declined. Mixed cultures of cortical cells and either skeletal muscle or various other non-neuronal cells exhibited a 40-100% enhancement in both acetylcholine and gamma-aminobutyric acid synthesis. Autoradiographic methods showed that a subpopulation of neurons in the cortical cultures accumulated gamma-aminobutyric acid from the medium.

Acetylcholine↗

Latamoxef: single agent prophylaxis in colorectal surgery.

To assess the suitability of latamoxef (moxalactam) as single agent chemoprophylaxis in elective colorectal surgery, 120 consecutive patients were randomized to receive latamoxef (L) 1 g or cephazolin 1 g and metronidazole 500 mg (CM) administered intravenously at induction of anaesthesia and 6 and 12 h postoperatively. The groups were well matched for age, sex, pathology and procedures. Serum and tissue levels of latamoxef were well above the MIC90 for most bowel organisms. Inpatient stay was similar for both groups. Pyrexia was seen in 44 patients (11 L, 23 CM) and eight developed a wound infection (3 L, 5 CM). Major intra-abdominal sepsis occurred in seven patients (2 L, 5 CM), secondary to anastomotic leakage in four (1 L, 3 CM). Twenty patients developed a chest infection (5 L, 15 CM) and eight urinary sepsis (2 L, 6 CM). No bleeding complication occurred, and there was no difference in clotting function between the two groups. Six patients died prior to follow-up at six weeks (1 L, 5 CM), two from anastomotic dehiscence. All but three wounds had healed (1 L, 2 CM) and one further patient had an incisional hernia (CM). These results suggest that latamoxef is an efficient chemoprophylactic agent in elective colorectal surgery, and is marginally better than cephazolin plus metronidazole.

Adult↗

Nonspecific small bowel ulceration.

Six patients (4 male, 2 female) developed nonspecific small bowel ulceration between the ages of 4 months and 76 y. Five had gastrointestinal haemorrhage, usually chronic and resulting in iron deficiency anaemia. Four had features of subacute intestinal obstruction; there were no perforations. A small bowel enema was the most useful single investigation for delineating the lesions, and surgical excision was curative in all but one case. No aetiological causes could be implicated, other than in one patient taking a daily tablet of Navidrex-K.

Adult↗

Gastrocnemius myositis in a patient with inflammatory bowel disease.

A young woman with long-standing inflammatory bowel disease presented with a tender left gastrocnemius myositis in association with an exacerbation of her disease. Muscle biopsy showed a chronic inflammatory cell infiltrate and atrophic muscle fibres, but no granulomata or vasculitis, and her symptoms responded to high-dose steroids. Twelve months later she underwent subtotal colectomy for troublesome symptoms and incidentally was discovered to have an adenocarcinoma of the sigmoid colon. Myositis without granulomata has not been reported previously in either Crohn's disease or ulcerative colitis.

Adenocarcinoma↗

Testicular exocrine malfunction after torsion.

The exocrine and endocrine functions of the testis were assessed in 67 patients a median of 4.0 years after unilateral torsion (range 3 months-12 years). Of 54 patients who underwent orchidopexy, some atrophy of the affected testis developed in 46; the degree of atrophy was significantly correlated with the duration of torsion (r = -0.56, p less than 0.001). The remaining 13 patients had undergone orchidectomy after a mean duration of torsion of 71 h. Seminal analysis was abnormal in 44 of 51 patients tested (86%), and the low total motile sperm count correlated with the duration of torsion (r = -0.53, p less than 0.001). Sperm counts were much lower in men with torsion for longer than 8 h than those with a shorter period of torsion (median 7.2 X 10(6) v 83.5 X 10(6); p less than 0.00003). Serum levels of luteinising hormone, prolactin, testosterone, and follicle-stimulating hormone were generally within normal limits. An acute ischaemic episode affecting only one testis causes bilateral loss of exocrine function in most patients, while endocrine function is preserved.

Adolescent↗