Biomedical subjects
J H Wyllie
Publications and source records attributed to J H Wyllie.
Stimulation of mucus output from rat colon in vivo.
Sodium chloride (155 mM) and N-acetyl cysteine (6 mM) were recirculated through the colons of anaesthetized rats. Mucus accumulated in the perfusion fluid which was changed at intervals to allow mucus output to be estimated by measurement of hexose. The output of mucus could be stimulated by intravenous administration of the cholinergic drugs carbachol and bethanechol; this effect was inhibited by atropine. Mucus output could also be stimulated by intravenous 5-hydroxytryptamine. This was not a muscarinic cholinergic effect because atropine did not prevent it. Neither did methysergide inhibit it; but chlorpromazine did. Precursors of 5-hydroxytryptamine, 5-hydroxytryptophan and L-tryptophan, also stimulated mucus output if given in high dosage. The results suggest that in this preparation mucus output can be stimulated by two distinct mechanisms, one cholinergic, the other involving 5-hydroxytryptamine and perhaps 5-hydroxytryptophan.
The pathology of a cricopharyngeal dysphagia.
The paper describes the changes in the cricopharyngeal muscle in seven cases of dysphagia resulting from obstruction at this level which was relieved by myotomy. Histological features included degeneration and regeneration in the muscle fibres with interstitial fibrosis which was severe in some of the cases. It is considered that this restrictive fibrosis is the cause of the dysphagia and that it is secondary to muscle fibre damage, the cause of which is at present obscure. Minor degrees of muscle damage and regeneration were seen rarely in controls and fibrosis was never present. There was no evidence of underlying vascular or neurological disease in six cases; the seventh had a previous history of scleroderma but this was not thought to be the cause of the cricopharyngeal lesion. The age incidence ranged from 1 to 5 years at the onset of dysphagia; in six of the seven it was 50 years or more.
Controlled trial of cimetidine in upper gastrointestinal haemorrhage.
One hundred and one patients were studied in a double-blind controlled trial to assess the role of oral cimetidine in preventing the continuation or recurrence of acute upper gastrointestinal haemorrhage from various sources, chiefly peptic ulcer. The dose of cimetidine was 800 mg on entering the study followed by 400 mg six hourly. The source of bleeding was identified endoscopically in 96% of patients, peptic ulcer comprising 70%. Bleeding continued or recurred in 11 of 51 (21.5%) of patients on cimetidine and in 12 of 50 (24%) of patients on placebo. Analysis of the effect of cimetidine according to age or severity of bleeding showed no significant advantage for the drug.
Double-blind comparison of cimetidine and placebo in the maintenance of healing of chronic duodenal ulceration.
Patients suffering from chronic duodenal ulceration were allocated at random to treatment with either cimetidine (400 mg twice daily) or matching placebo for six months. Before entry to the trial all patients were shown to have healed ulcers on endoscopy. Most of the patients had participated in a one-month trial of cimetidine during which their ulcers healed. The trial showed that four of 29 patients relapsed on maintenance treatment with cimetidine, which therefore did not confer complete immunity from relapse. However, cimetidine treatment was very much better than placebo treatment, on which 18 of 31 patients relapsed. Of the 22 patients who relapsed clinically, 20 were submitted to endoscopy and 19 of these were shown to have ulcerated again. Endoscopy at the end of the trial showed that ulcers had also redeveloped in five of 28 asymptomatic patients. Length of previous dyspeptic history had no bearing on the results of the trial but there was evidence that relapse on placebo was less likely if the ulcer had originally healed on a high dose of cimetidine. Clinical relapse was associated with worsening duodenitis. Symptoms, clinical observation, and laboratory tests showed no important abnormalities in the patients.
The spectrum of inhibition of gastric acid secretion.
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Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat.
1 The rat hindquarter preparation, as described, responds with reproducible vasoconstriction to noradrenaline and tryptamines. 2 The receptors involved in these responses are distinct. 3 Evidence of heterogeneity of tryptamine receptors was not obtained. 4 The 5-hydroxytryptamine (5-HT) antagonists, methysergide and cyproheptadine, although very potent, displayed antagonism of a non-competitive type whereas a series of phenothiazines and phentolamine displayed competitive antagonism against 5-HT. 5 For the phenothiazines the order of increasing potency was promazine less than chlorpromazine less than triflupromazine.
Stimulation of colonic mucus output in the rat [proceedings].
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Maintenance treatment of duodenal ulcer with cimetidine.
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Histamine H2-receptor antagonist in treatment of peptic ulcer.
Cimetidine promotes the healing of duodenal ulcer, but prolonged use (perhaps in low dosage) seems to be necessary in many cases to prevent relapse. H2 receptors are widely distributed in body tissue, but important effects of blockade of the extragastric receptors have not been detected. Nor has serious toxicity been noted. Cimetidine probably will become a familiar, much-used, and valuable drug.
Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat [proceedings].
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Comparison of catgut and polyglycolic acid sutures in colonic anastomoses.
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Bioassay and radioimmunoassay of gastrin and significance of gastrin degradation products.
Inactivation of gastrin was studied (a) in vitro by incubation with a high-speed supernatant fraction of rat small bowel mucosa and (b) in vivo by perfusing gastrin through the small bowel vascular bed in anaesthetized dogs. In both types of experiment there was a highly significant loss in the bioactivity of gastrin, but no significant change in its immunoreactivity. This showed that gastrin was inactivated by a subtle chemical change which rendered the molecule biologically inactive, yet left its immunoreactivity unimpaired.
Drugs for peptic ulcer.
Conservative management of peptic ulcer relies on the use of drugs as an adjuvant to the time-honored measures of avoiding stress, reducing gastric secretion, and regulating the diet. Alkalies neutralize acid and anticholinergic drugs partly inhibit secretion.. Both are widely used but are often inadequate to control symptoms. Carbenoxolone appears to have a more specific effect in promoting healing of gastric ulcers and has now been used for 15 years. Its role in the treatment of gastric ulcer can be critrically examined, particularly in relation to how this influences surgical management. Recently introduced compounds know as histamine H2-receptor antagonists have a profound effect in inhibiting gastric secretion. Early experience in patients with duodenal ulcer indicated the efficacy of these compounds in promoting healing. These potent new drugs are likely to influence strongly the management of patients with duodenal ulcer, and this may affect the indications for surgery.
Intravenous metronidazole in amoebic enterocolitis.
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Treatment of duodenal ulcer with cimetidine.
In a small open trial nineteen patients with active duodenal ulceration shown by fibreoptic endoscopy were treated with a 6-week course of cimetidine 1.6 g daily. Seventeen had healed ulcers on repeat endoscopy at 6 weeks. Seven of these have relapsed symptomatically within a month of withdrawal of cimetidine. No statistically significant change in the haemoglobin, white-blood-cell count, urea and electrolytes, or liver-function tests was associated with treatment. Plasma-creatinine showed a very small but significant rise but the mean level remained within the normal range. The significance of this is not clear.
Clinical experience with metiamide.
The new histamine H2-receptor antagonist, metiamide, was shown to inhibit acid and pepsin secretion in gastric secretion studies performed on patients suffering from peptic ulceration. The new drug was administered intravenously in these experiments, but effective plasma levels could also be produced by oral administration. When symptomatic patients were treated with the drug nearly all experienced marked symptomatic relief, and there was some evidence that ulcer healing occurred during treatment. When the drug was withdrawn symptoms tended to return. No toxic reactions were encountered in this trial. Double-blind studies are now being made in Britain to establish the place metiamide may have in the treatment of duodenal ulceration.
Proceedings: Histamine receptors in human skin.
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