Search PubMed⌕ Search

Biomedical subjects

J Calam

Publications and source records attributed to J Calam.

At least 127 records · Page 7Linked to original sources
PubMed1988

Four-dimensional phosphorus-31 chemical shift imaging of carcinoid metastases in the liver.

Four-dimensional chemical shift imaging was used to map spatial variations in phosphorus metabolites in a patient with carcinoid metastases in the liver. The results were compared to those from an age and sex matched volunteer, with no known previous history of liver disease. In the patient local abnormalities were observed. These included elevated phosphomonoester and decreased phosphodiester concentrations relative to adenosine triphosphate. The regions of abnormality corresponded to regions containing metastases identified with x-ray computed tomography and magnetic resonance imaging.

Adult↗
PubMed1988

Cholecystokinin cleavage to cholecystokinin-octapeptide in vivo and in vitro: accelerated cleavage in acute pancreatitis.

We have examined the possibility that the 33- and 39-amino acid forms of cholecystokinin (CCK) are cleaved to produce CCK-octapeptide (CCK-8) during circulation in humans. When a mixture of the 33- and 39-amino acid forms of porcine CCK was infused at 0.1-2.5 pmol/kg.min into normal subjects, material indistinguishable from CCK-8 by gel filtration and in region-specific radioimmunoassays appeared in plasma, together with an intermediate form that eluted between the 33- and 8-amino acid peptides. During infusions, plasma concentrations of CCK-33/39, CCK-8, and the intermediate CCK rose to 63 +/- 26 (mean +/- SE), 57 +/- 12, and 18 +/- 10 pmol/L, respectively. Cholecystokinin-octapeptide appeared rapidly and constituted approximately 40% of total CCK-like immunoreactivity after 5 min of infusion. Octapeptide-like material also appeared, but at a slower rate, when CCK-33 was incubated at 37 degrees C with human plasma. Thus after 5 min, and throughout the incubation, CCK-8 comprised approximately 20% and CCK-33 approximately 75% of total immunoreactivity. Cholecystokinin-33 disappeared more rapidly and small forms appeared in higher concentrations in plasma from patients with acute pancreatitis. Thus, after incubation for 120 min, CCK-33 and CCK-8 comprised 45% +/- 7% and 13% +/- 3% of initial immunoreactivity in normal plasma, but 18% +/- 6% and 33% +/- 9%, respectively, in plasma from patients with pancreatitis. Ethylenediaminetetraacetic acid, but not aprotinin, inhibited the cleavage of CCK-33 to produce CCK-8, and the degradation of CCK-8 in normal plasma in vitro.

Acute Disease↗
PubMed1988

Peptide histidine methionine (PHM) increases ileostomy output.

The human vasoactive intestinal peptide (VIP) gene also encodes peptides histidine methionine (PHM) which has substantial sequence homology with VIP. Both are present in nerve fibers in the human ileum and circulate in greatly increased concentrations in patients with the watery diarrhoea syndrome. We have infused PHM (23 pmol/kg/min) into 5 patients with ileostomies to determine the effect of PHM on human ileal output. Plasma PHM levels rose from 22 +/- 6 to 6013 +/- 874 pM (mean +/- S.E.M.) during PHM infusions and ileal output rose from 16 +/- 3 to 177 +/- 27 g/30 min (P less than 0.0001). PHM infusions also produced a significant fall in the percentage of solid material and a rise in the concentration of chloride in the ileal effluent. Mean plasma PHM concentrations during PHM infusions were equal to the highest levels seen in patients with the watery diarrhoea syndrome, so PHM may contribute to diarrhoea in this condition. Neuronal PHM may exert physiological control over ileal transport of water and electrolytes.

Chlorides↗
PubMed1988

Effects of vasoactive intestinal polypeptide infusions on renal function in patients with liver disease.

1. The effect of intravenous vasoactive intestinal peptide (VIP, 6 pmol/kg per min) on renal function in six patients with cirrhosis of the liver was examined. 2. VIP caused generalized vasodilation and increased plasma renin activity, but diminished the glomerular filtration rate by about one third. 3. The excretion of water, sodium, potassium and calcium also fell significantly. 4. These results differ from our findings in normal man in whom VIP diminished water and electrolyte secretion largely by increasing tubular reabsorption. 5. It is concluded that the elevated VIP levels present in patients with severe liver disease may affect renal function, but that the presence of liver disease may affect renal responses to VIP.

Blood Cell Count↗
PubMed1987

Renal function during bovine neurotensin infusion in man.

The peptide hormone neurotensin (NT) is found mainly in gut endocrine cells of the ileum, but has also been identified as a putative neurotransmitter in the central and peripheral nervous systems. It may have a dual role as a circulating gastrointestinal hormone and peripheral neurotransmitter. Its predominant effects are to reduce oesophageal sphincter tone, inhibit gastric secretion and emptying and inhibit intestinal motility, but stimulate intestinal and pancreatic exocrine secretion; NT-like immunoreactivity has been found in kidney and therefore NT may influence renal function. When infused i.v. in rabbits it causes antinatriuresis. We have studied its renal effects in 11 healthy males by i.v. infusion under conditions of altered dietary sodium. Postprandial circulating neurotensin levels were reproduced by infusion. There were no consistent systemic or renal haemodynamic effects. Plasma electrolytes and renin did not change. Only renal chloride excretion changed significantly, falling by ca. 30%, and recovering after infusion. There is no evidence for a specific renal tubular chloride transport mechanism, but coupled cotransport, Na+:K+:2CI-, may be hormonally regulated. NT might stimulate this process and contribute to the renal response to changes in dietary composition, especially sodium intake.

Adult↗
PubMed1987

Raw soya-bean flour increases cholecystokinin release in man.

1. The aim of the present study was to determine whether oral ingestion of raw soya-bean flour, which contains trypsin inhibitors, alters the release of cholecystokinin (CCK) in man. 2. Eleven healthy volunteers ate two mixed meals: one with raw soya-bean flour and the other with soya-bean flour that had been heat-treated. The two flours inhibited 34 and 3 mg trypsin/g flour respectively. 3. CCK was measured in plasma using a bioassay based on the release of amylase (EC 3.2.1.1) from dispersed rat pancreatic acini. 4. The peak CCK response was 16.8 (SE 8.1) pmol/l with raw soya-bean flour but 4.9 (SE 2.8) pmol/l with heat-treated flour (P less than 0.05). 5. We conclude that ingestion of raw soya-bean flour increases CCK release in man and that heat treatment which reduces the trypsin inhibitor content of the flour also diminishes its CCK-releasing effect.

Adult↗
PubMed1987

SMS 201-995 treatment and advanced intestinal cancer: a pilot study.

The hypothesis that somatostatin, a compound with antitrophic effects on the gastrointestinal tract, may affect beneficially the progression of advanced intestinal cancer has been tested in a small pilot study. Ten patients, four with advanced pancreatic cancer, four with advanced colorectal cancer and two with gastric cancer, were treated with a long-acting analogue of somatostatin, SMS 201-995, 50, 100 micrograms subcutaneously twice daily. There were no clinical, radiological or biochemical indicators of a response to this treatment. There are no indications from this study that hormonal manipulation alters the rate of growth of advanced gastrointestinal cancer.

Adult↗
PubMed1987

Effects of indomethacin and (+/-)-propranolol on the cardiovascular and renin responses to vasoactive intestinal polypeptide (VIP) infusion in man.

The mechanisms of the cardiovascular and renin responses to vasoactive intestinal polypeptide (VIP) are unclear. Rabbit studies suggest that VIP-induced tachycardia is largely beta-adrenoceptor mediated, but that the renin response may be partially prostaglandin-dependent. To examine the relative importance of prostaglandins and reflex sympathetic activation in the haemodynamic and renin responses to VIP infusion in man, we completed two randomised single-blind crossover studies in two groups of six healthy male volunteers (aged 24-35 years). We recorded the effects of indomethacin and propranolol pretreatment on VIP-related changes in heart rate (HR), blood pressure (BP), forearm vascular resistance (FVR), plasma renin activity (PRA), plasma noradrenaline (PNA) and plasma arginine vasopressin (AVP) concentrations. Intravenous VIP (calculated dose: 6 pmol kg-1 min-1) produced cutaneous flushing, increased HR and PRA, decreased FVR, but did not alter mean arterial BP or AVP levels. Indomethacin (375 mg over 3 days) lowered basal PRA and propranolol (circa 40 mg i.v. over 60 min) decreased resting HR and increased FVR. Although indomethacin and propranolol reduced the absolute rise in PRA and HR, respectively, during VIP infusion, the percentage changes were no different from control. Neither drug altered the flush response to VIP and propranolol did not affect the fall in FVR. We conclude that the measured cardiovascular responses to VIP infusion in man are probably direct and do not involve a significant contribution from reflex sympathetic stimulation, nor prostaglandin release.

Adult↗
PubMed1987

Renal effects of gastrin C-terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man.

Pentagastrin and cholecystokinin octapeptide (CCK8) were infused i.v. at three different doses in two sets of 4 conscious rabbits following a repeated measurements design (130, 1,300 and 13,000 pmol kg-1 min-1 pentagastrin; 5, 50 and 450 pmol kg-1 min-1 CCK8). In man, two different doses of pentagastrin (13 and 65 pmol kg-1 min-1) were infused in two groups of 6 subjects, and CCK8 (2 pmol kg-1 min-1) in a third group. According to published human postprandial levels, plasma CCK8-like immunoreactivity concentrations were supraphysiological at all doses infused. In the rabbit, pentagastrin produced a dose-related fall in urine flow and free water clearance, but no significant change in systemic and renal haemodynamics, electrolyte excretion and measured plasma constituents; however, in human subjects, pentagastrin increased renal sodium excretion and reduced potassium excretion but did not change glomerular filtration rate. In the rabbit, CCK8 produced a dose-related fall in plasma renin activity, plasma calcium concentration and mean arterial blood pressure; dose-dependent increases in effective renal plasma flow, glomerular filtration rate and renal sodium excretion. In man, changes in sodium and potassium excretion similar to pentagastrin were observed; there were no significant changes in plasma renin activity, plasma calcium concentration, blood pressure, effective renal plasma flow or glomerular filtration rate. The pharmacological renal effects of pentagastrin in conscious water-loaded rabbits resemble vasopressin. In contrast, CCK8's most striking effect was vasodilatation and was unusual in inhibiting rather than stimulating renin release. In man the net changes in urine composition found during infusion of these peptides are similar to those produced by the potassium-sparing diuretics, amiloride and triamterene. However the generally weak renal effects observed, even at pharmacological doses, indicate that these peptides are unlikely to influence renal function under normal physiological conditions.

Adult↗
PubMed1987

Effects of substance P and other neuropeptides on guinea-pig gall-bladder muscle.

Substance P, neurotensin, bombesin and neuropeptide-Y-like immunoreactivities have been identified in nerves in gall-bladder muscle, so we studied the effects of these peptides on guinea-pig gall-bladder muscle in vitro. Substance P (0.1 mumol/l or greater) contracted gall-bladder muscle. Studies with specific antagonists indicated that the response did not involve intramural nerves or the release of acetylcholine, cholecystokinin or histamine. Field stimulation of intramural nerves caused contraction of gall-bladder muscle, but this was unaffected by a substance P antagonist and abolished by atropine. Thus, although substance P contracts gall-bladder muscle by a direct effect, this peptide does not appear to be involved in nerve-mediated gall-bladder contraction. Neurotensin, bombesin and neuropeptide Y had no effect on this preparation.

Animals↗
PubMed1986

Effects of benzodiazepines on responses of guinea-pig ileum and gall-bladder and rat pancreatic acini to cholecystokinin.

Bradwejn and De Montigny have recently shown that benzodiazepines selectively inhibit excitation of hippocampal neurones by cholecystokinin (CCK). We show here that lorazepam and chlordiazepoxide selectively inhibit the nerve-mediated response of ileal longitudinal muscle to CCK, but have no effect on the direct stimulation of gall-bladder muscle or pancreatic acini by this peptide. Lorazepam (1 and 10 microM) and chlordiazepoxide (0.1 and 1 microM) inhibited responses of guinea-pig ileum, but not gall-bladder to CCK. Responses of both tissues to acetylcholine (ACh) were unaffected and lorazepam (10 microM) did not inhibit ileal responses to neurotensin, 5-hydroxytryptamine and substance P which act entirely or in part by stimulating myenteric nerves. Chlordiazepoxide (1 and 10 microM) did not inhibit CCK-stimulated amylase release from dispersed rat pancreatic acini. Higher concentration of the same drugs and diazepam (1 and 10 microM) which has high affinity for benzodiazepine receptors on gastrointestinal muscle, inhibited responses of ileum and gall-bladder to both CCK and acetylcholine.

Acetylcholine↗
PubMed1985

Acid and gastrin responses during intragastric titration in normal subjects and duodenal ulcer patients with G-cell hyperfunction.

Amino acid induced acid and gastrin responses during intragastric titration at pH 2.5 and 5.5 were compared in normal subjects and duodenal ulcer patients with G-cell hyperfunction. The latter were identified on the basis of raised basal or maximal acid outputs and increased gastrin responses to feeding. In normal subjects the mixed amino acid meal stimulated only modest increases in serum gastrin, and the highest observed increase was about 30% that after a standard meal. In contrast, in the G-cell hyperfunction group the highest gastrin concentrations were similar to those after a standard meal. In the G-cell hyperfunction group the increment in serum gastrin at pH 2.5 expressed as a proportion of that at pH 5.5 was 0.29 indicating that the capacity of acid to inhibit gastrin release was well established in these patients. Acid secretory rates were close to maximal at both pH 2.5 and 5.5 during intragastric titration in the ulcer patients, but in normal subjects acid output was about 50% maximal at 2.5 and close to maximal at 5.5. The results suggest that the enhanced gastrin response to feeding in G-cell hyperfunction patients is because of increased sensitivity to amino acid stimulation rather than to diminished acid-inhibitory mechanisms.

Adult↗
PubMed1985

Future treatment of peptic ulcers.

Drugs which abolish acid secretion and promise improved ulcer healing rates have produced dysplasia and tumours in experimental animals given large doses for long periods. Solutions to this problem will be based on better understanding of the mechanisms involved. Healing rates might be improved by combining inhibitors of acid secretion with ulcer protectors which, unlike currently available agents, are designed to work well in the presence of diminished acid secretion. Drugs which increase mucosal defence might best be used to prevent ulceration, so the need is to develop agents which are safe for long term use.

Animals↗
PubMed1983

Neurotensin stimulates defaecation.

Five normal adults defaecated within 2 1/2 hours of receiving neurotensin 13.5 pmol kg-1 min-1 for 30 min, whereas none did so after control infusions, in a double-blind study. Neurotensin caused borborygmi and production of stools which resembled the normal contents of the proximal and distal colon in terms of consistency and electrolyte content. This evidence suggests that neurotensin had a major effect on propulsive colonic motility. Blood neurotensin concentrations during infusion were about three times higher than normal postprandial concentrations, but plasma neurotensin is raised in some diseases associated with diarrhoea.

Adult↗
PubMed1983

Studies on the renin response to vasoactive intestinal polypeptide (VIP) in the conscious rabbit.

Vasoactive intestinal polypeptide (VIP) has been found within the renal cortex and is believed to be a neurotransmitter. Although it produces systemic vasodilatation and renin release, the exact mechanism of the latter response is uncertain. When infused into conscious rabbits, VIP elicits a rise in plasma renin activity (PRA) and an increase in heart rate. The rise in PRA is unaltered by pretreatment with propranolol, but is attenuated by indomethacin. The tachycardia is inhibited by propranolol, but unaffected by indomethacin. We conclude that the renin response to VIP is in part prostaglandin-dependent and that the heart rate response is due to direct or reflex beta-adrenoceptor stimulation.

Adrenergic beta-Antagonists↗
PubMed1983

Effects of vasoactive intestinal polypeptide on renal function in man.

Six healthy males received vasoactive intestinal polypeptide (VIP; 6 pmol kg-1 min-1) by intravenous infusion for 90 min, with 60 min control periods before and after. Plasma VIP levels rose by about 100 pmol l-1 during the infusion. VIP produced changes in heart rate and blood pressure consistent with generalized vasodilatation, but there were no significant changes in effective renal plasma flow or glomerular filtration rate. Both plasma solids and haematocrit rose by about 5%, suggesting that haemoconcentration had occurred during VIP infusion. Urine flow fell to about a third, and the fractional excretion of sodium, potassium, chloride and calcium fell to between half and two-thirds of control values. Fractional excretion of phosphate did not fall significantly. Plasma renin activity rose about 3-fold during VIP infusion.

Adult↗