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Biomedical subjects

A R Cooke

Publications and source records attributed to A R Cooke.

At least 19 recordsLinked to original sources

Does 5-hydroxytryptamine influence "purinergic" inhibitory neurons in the intestine?

Intrinsic inhibitory neurons to guinea pig taenia coli and small bowel circular muscle were activated by transmural electrical stimulation, and the postinhibitory contractile response of the muscle was utilized to evaluate whether or not the neuronal action of 5-hydroxytryptamine (5HT) was associated with the inhibitory neurons. The postinhibitory contractile responses of the small intestinal circular muscle were unaffected by 5HT. The 5HT antagonist methysergide also did not affect the poststimulus contractile response of the circular muscle. The amplitude and area under the contractile curve of the poststimulus contractile response of the taenia coli were reduced and the amplitude of the relaxation response to electrical stimulation was increased in one-half of the preparations after application of 5HT. Methysergide did not alter the poststimulus contractile response of the taenia coli. 5HT is implicated as a neurotransmitter substance for slow synaptic excitation within the enteric nervous system of the guinea pig small intestine; however, the 5HT synapses do not appear to be present on the "purinergic" inhibitory neurons nor on neurons that synaptically influence the inhibitory neurons.

Animals

Laboratory aids in the diagnosis of pancreatitis.

The diagnosis of both acute and chronic pancreatitis continues to be a challenge despite the development of new techniques and the refinement of old methods. The problem is best approached by the application of a combination of tests which can provide a reasonable degree of sensitivity and specificity applicable to the different forms of pancreatitis. In acute pancreatitis an elevation of serum amylase and amylase/creatinine clearance ratio is diagnostically useful. In chronic pancreatitis, several tests are needed to enhance the diagnostic yield, and such tests can include the secretin-pancreozymin test, ERCP, fecal fat measurement, Lundh test meal, and the administration of the synthetic peptide BZ-Ty-PABA.

Acute Disease

Effects of some gastrointestinal hormones on two muscle layers of duodenum.

The duodenums of opossums and cats were cut into strips 2 mm wide and 2-2.5 cm long. Strips cut in the oral-caudal axis were called longitudinal strips; those cut at 90 degrees to that axis were called circular strips. Cholecystokinin (CCK) and cerulein stimulated phasic contractions of circular muscle of opossum duodenum, but had no effect on the longitudinal muscle. The effect of CCK was not blocked by tetrodotoxin (10(-7)M), indicating a direct muscle stimulation. CCK had no effect of both muscle layers of the cat duodenum. Vasoactive intestinal peptide raised tension in longitudinal muscle, but reduced tension in circular muscle of opossum duodenum. Glucagon slightly reduced tension in both longitudinal and circular muscle of opossum duodenum. It also inhibited contractions of circular muscle caused by acetylcholine. Pentagastrin and secretin had no effect on either muscle layer in either species. These findings suggest that the circular and longitudinal muscle layers of the duodenum respond differently to at least some gastrointestinal hormones. Also, there is species variation in response to gastrointestinal hormones.

Animals

Parallel pathways for ion transport across rat gastric mucosa: effect of ethanol.

Transmural fluxes of 22Na or 36Cl across the isolated rat gastric mucosa were measured simultaneously with [3H]mannitol in an attempt to separate transmural ionic movement into cellular and noncellular components. The relationships between mannitol flux and the fluxes of Na and Cl are characteristic of simple diffusion, suggesting that mannitol traverses the isolated epithelium largely via noncellular pathways. The total tissue conductance can be described as the sum of two components, one of which is highly correlated with the transmural mannitol flux and presumably represents the conductance of a noncellular leak path. The cellular components of the mucosa-to-serosa Na flux and of both Cl fluxes are highly correlated with the short-circuit current. Exposure of the mucosal surface of the epithelium to 4% ethanol reduces the short-circuit current and increases the electrical conductance. Ethanol inhibits the active transport of Na and Cl and increases the apparent permeability of noncellular pathways for transmural ionic diffusion.

Animals

Chronic hepatitis.

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Adrenal Cortex Hormones

Pulmonary alveolar microlithiasis.

A case of pulmonary avleolar microlithiasis is reported. This is of especial interest as it is the first case to be reported from Africa South of the Sahara. The clinical presentation of the patient follows a similar pattern as that of cases already described by other workers. The diagnosis in this case was made in life by a combination of radiological examination and a lung biopsy. The clinical presentat on and aetiology of the condition are briefly discussed.

Calculi

A comparison of intrinsic nerve supplies of two muscular layers of duodenum.

The duodenums of opossums and cats were cut into strips 2 mm wide and 2-2.5 cm long. Strips cut in the direction of the oral-caudal axis were called longitudinal strips, and those cut at 90 degrees to that axis were called circular strips. Each muscle strip was stimulated with trains of electrical rectangular pulses (10 Hz, 50-70 V, 0.5 ms). In the longitudinal strips, electrical field stimulation caused contraction, and this contraction was abolished by atropine, 10(-7) M. In the circular strips, electrical field stimulation caused relaxation. This relaxation was abolished by tetrodotoxin, 10(-7) M, but it was not affected by antagonists to adrenergic and cholinergic transmission, nor by some gastrointestinal hormones. Reserpinization of the opossums or alteration of the frequencies of electrical field stimulation from 0.1-50 Hz did not affect or alter the relaxation of the circular strips or the contraction of the longitudinal strips. These findings suggest that the longitudinal muscle is dominated by an excitatory cholinergic innervation, and the circular muscle is dominated by a nonadrenergic, noncholinergic inhibitory innervation.

Animals

Gastric and duodenal ulcer and their associated diseases.

Assessments of likely associations between ulcer and other diseases are hindered by the frequent lack of controls, by controls which are inadequate, and by inadequate descriptions of techniques used. The inherent biases in some of the techniques have also probably been insufficiently appreciated. Ulcer is common in the community and much of the evidence adduced to suggest ulcer/other-disease associations may well be describing oridinary ulcer frequency which has been underestimated. With such problems in mind, few of the proposed associations bear examination. Ulcer is probably unusually frequent in patients undergoing treatment for chronic renal failure. It is possibly more frequent in association with hyperparathyroidism and in cirrhotics, in cardiovascular disease (except hypertension), and in chronic respiratory disease. Evidence for other associations is not compelling.

Adrenocortical Hyperfunction

Effect of a fixed pyloric opening on gastric emptying in the cat and dog.

The effect of preventing pyloric closure on the rate of gastric emptying without alteration of the gastroduodenal junction was studied in six dogs and four cats with gastric fistulas. Each had a Teflon cannula with an internal diameter of 1.0 or 1.25 cm (dog) and 0.6 cm (cat) sewn into the pyloric channel. At the completion of the initial series of tests, the cannulas were removed and the studies repeated. Test meals were 240 and 480 ml of water, acid (120 mM HC1), and hyperosmotic glucose (555 mM) in the dogs and 50 ml of water, acid (100 mM HC1) and fat (20 mM Na oleate) in the cats. Phenol red was used as a nonabsorbable marker. The residual volumes were collected at 15-40 min in the dogs and 15-20 min in the cats. In both species, the rate of emptying of all the meals was unaffected by the pyloric cannula. In the dog, added secretions were greater with the pyloric cannula in place, suggesting reflux of duodenal contents. This study indicates that while the pylorus is unimportant in the gastric emptying of liquids in the dog and cat, it may have a role in prevention of duodenal reflux.

Alcohols

Osmoltye and tryptophan receptors controlling gastric emptying in the dog.

The effect of three monosaccharides, three disaccharides, two dipeptides, combinations of tryptophan with two hexoses, one hexitol, and two amino acids ongastric emptying was studied in dogs to further define the samll intestinal receptors responsive to osmolytes and tryptophan. On a molar basis the disacchardies and dipeptides were almost twice as potent as their respective constituent monosaccharides or amino acids implying that the osmoreceptor is deep to the brush border disaccharidases and cytosol dipeptidases. Tryptophan probably acts by a mechanism different from the osmoreceptor since slowing of gastric emptying by tryptophan was inhibited by methionine which has no effect on a stimulant of the osmoreceptor mechanism. Lysine unlike methionine does not share the neutral amino acid transport pathway with tryptophan. Lysine did not change the inhibitory effect of tryptophan on gastric emptying. This imples that transport of tryptophan into the intestinal cell is necessary for its slowing effect. Glucose and galactose also inhibited the tryptophan effect whereas a nonabsorbed hexitor, mannitol, was without effect. Interference by the hexoses was also probably by competition with tryptophan for transport into the cell. These studies further indicate that the tryptophan receptor is different from the osmoreceptor.

Alanine

Drugs and gastric damage.

The effects of aspirin, salicylate formulations and substitutes, smoking (nicotine), indomethacin, corticosteroids, phenylbutazone, ethanol, caffeine and reserpine on the gastric mucosa are discussed. The damaging effects of the drugs are considered in terms of the gastric mucosal barrier, gastric erosions, microbleeding and haematemesis and melaena and finally whether they cause peptic ulcer. There is suggestive evidence that unbuffered aspirin is a cause of haematemesis and melaena and of gastric ulcer but the incidence rates for hospital admission are low, being 10 to 15 per 100,000 heavy users per year. Aspirin in solution as acetylsalicylate buffered to maintain a neutral pH protects against gastric damage. Newer aspirin substitutes (mefenamic acid, fenoprofen, naproxen, tolmetin and ibuprofen) appear to cause less faecal blood loss than aspirin but their long-term effects have not been fully evaluated. Smoking is definitely associated with peptic ucler but the mechanism is unknown. Corticosteroids are probably not ulcerogenic despite clinical bias that they are. Indomethacin and phenylbutazone may be ulcerogenic but there is insufficient evidence to make firm judgements. Ethanol, caffeine and reserpine, on available evidence, are probably not ulcerogenic.

Adrenal Cortex Hormones

Effect of tryptophan and its metabolites on gastric emptying of liquid meals in dogs.

The effects of tryptophan and its metabolites were studied to determine whether the known inhibiting effect of tryptophan on emptying was due to local or systemic effects or due to tryptophan metabolites. In five dogs with chronic gastric fistulas, instillation of 300 ml of DL-kynurenine (5mM), 5-hydroxytryptophan (mM), or 5-hydroxytryptamine (20 mM) into the gut did not slow gastric emptying. Furthermore, iv infusion of L-tryptophan (5, 20, 50 mM), DL-kynurenine (2, 5, 10 mM), 5-hydroxytryptamine (2mM, 10 mM), and 3-indolepyruvic acid (2, 5, 10 mM) also did not slow gastric emptying. These studies indicate that tryptophan slows gastric emptying by exciting a receptor in the gut and not by a direct effect on the stomach or brain or via its major metabolites.

Animals