Helicobacter pylori and peptic ulcers: the present position.
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Animals↗
Biomedical subjects
J Calam
Publications and source records attributed to J Calam.
Suppression of Helicobacter pylori reduces gastrin releasing peptide stimulated gastrin release in duodenal ulcer patients.
Helicobacter pylori increases gastrin release in duodenal ulcer patients. This may be through disruption or changes in the mucus layer affecting the access of luminal stimulants to gastrin releasing cells. The effect of suppressing H pylori on gastrin release stimulated by a non-luminal stimulus, gastrin releasing peptide (GRP), was examined. Eleven patients with active duodenal ulcer disease and colonised with H pylori received an intravenous infusion of GRP (2.9 pmol/kg/minute for 30 minutes) and the plasma gastrin response was measured. Basal and peak pentagastrin stimulated acid output were also determined. Patients were treated with tripotassium dicitratobismuthate (De-Nol) and metronidazole to suppress H pylori and the tests were repeated. Suppression of H pylori decreased plasma gastrin concentrations during GRP infusion, but acid output was not affected. Chromatographic analysis of the forms of gastrin in plasma showed a significant fall in gastrin 17, the predominant form found in the gastric antrum. Gastrin 34 did not fall significantly. This study shows that suppression of H pylori decreases the hypergastrinaemia caused by the nonluminal stimulant, GRP, mainly via decreasing gastrin 17.
Adult↗
Gastric antral vascular ectasia: maintenance treatment with oestrogen-progesterone.
Gastric antral vascular ectasia ('watermelon stomach') is a rare cause of chronic gastrointestinal bleeding and various medical and surgical treatments have been described. We report a patient in whom an oestrogen-progesterone preparation successfully controlled recurrent blood loss.
Aged↗
Role of cholecystokinin in pancreatic adaptation to massive enterectomy.
Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation.
Animals↗
Effects of peptide YY on the human cardiovascular system: reversal of responses to vasoactive intestinal peptide.
Peptide YY (PYY) reverses the increased intestinal secretion stimulated by vasoactive intestinal peptide (VIP) in humans. VIP also dilates blood vessels, so we investigated the effect of PYY on the cardiovascular system. Six volunteers received PYY, 0.4 and 1.2 pmol.kg-1 x min-1 i.v. for 2 h, reproducing plasma levels seen postprandially and during a diarrheal illness, respectively. Cardiac function was assessed by echocardiography. PYY infused at 0.4 pmol.kg-1 x min-1 had no effect on cardiovascular parameters. PYY infused at 1.2 pmol.kg-1 x min-1 caused a fall in both stroke volume from 128 +/- 8 to 110 +/- 8 ml/beat (mean +/- 95 confidence interval, P < 0.01) and cardiac output from 7.2 +/- 0.4 to 6.1 +/- 0.4 l/min (P < 0.01). Effects of infusion of PYY into the brachial artery at doses of 0-16 pmol/min were assessed using venous occlusion plethysmography in six subjects. PYY infusion caused a dose-dependent fall in forearm blood flow. Six subjects received VIP, 5 pmol.kg-1 x min-1 i.v., causing a rise in heart rate from 55 +/- 3 to 70 +/- 3 beats/min and increased cardiac output from 7.3 +/- 1.1 to 13.1 +/- 1.1 l/min. The addition of PYY, 0.4 pmol.kg-1 x min-1 i.v., did not affect the heart rate significantly but decreased the cardiac output to 10.4 +/- 1.1 l/min (P < 0.01). Infusions of PYY into the brachial artery at 5 pmol/min decreased local vasodilation induced by VIP infused at 2 pmol/min at the same site by 40% (P < 0.01), even though this dose of PYY had no significant effect on local blood flow when given alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
pH-dependent secretion of gastrin in duodenal ulcer disease: effect of suppressing Helicobacter pylori.
Patients with duodenal ulcers and Helicobacter pylori infection have elevated plasma gastrin concentrations which fall after suppression of the organism. This may be due to H. pylori elevating the pH of the antral mucous layer, therefore preventing luminal acid from inhibiting gastrin release. To test this idea, we measured the plasma gastrin concentrations under basal conditions and in response to 4% peptone when the gastric lumen was maintained at pH 2.5 and at pH 5.5 by gastric perfusion. We studied 11 duodenal ulcer patients before and after suppression of H. pylori. Gastrin concentrations were significantly higher before suppression of H. pylori than after treatment in all three states; basal gastrin (pmol/l) fell from 9.2 (3.7-23, median and range) to 5.1 (1.7-15) after treatment; from 11.3 (3.8-29) to 5.9 (5.7-6.1) at pH 2.5 and from 15.2 (3.9-32) to 7.15 (6.1-14) at pH 5.5. The ratio of peptone-stimulated gastrin at pH 2.5/pH 5.5 was similar before (0.8; 0.5-1.7) and after (0.8; 0.5-1.1) suppression of H. pylori. These results indicate that infection with H. pylori increases basal and peptone-stimulated plasma gastrin concentrations, and that this response is independent of luminal pH.
Amoxicillin↗
Assessment of gall bladder dynamics, cholecystokinin release and the development of gallstones during octreotide therapy for acromegaly.
The development of gallstones is a well recognized complication of therapy with the long-acting somatostatin analogue, octreotide in patients with acromegaly. A group of nine acromegalic patients was treated with octreotide at doses of 300-600 micrograms daily for 8 months and the changes in fasting and post-prandial cholecystokinin release, and gall bladder motor function (determined by a radiosotopic technique) were assessed at regular intervals. In addition the development of any gallstones was determined by serial ultrasonography. Fasting cholecystokinin levels showed no significant change over 6 months, whereas the post-prandial levels demonstrated a significant decrease (p less than 0.01) during therapy, yet remained significantly higher than fasting levels. Twenty-four hours after commencing therapy gall bladder ejection fraction was decreased by 57 +/- 23 per cent and gall bladder ejection rate decreased by 63 +/- 19 per cent compared to the pretreatment values, whereas after 6 months' therapy a marked reduction in gall bladder ejection fraction (greater than 35 per cent) and gall bladder ejection rate (greater than 40 per cent) persisted in only four of nine patients. Three of these four patients with persistently impaired gall bladder motor function were subsequently shown to have developed either gallstones or biliary sludge during the course of therapy. We conclude that treatment with octreotide is associated with an impaired post-prandial release of cholecystokinin in all acromegalic patients, but gallstones only develop in those patients who, in addition, have evidence of a persistently impaired gall bladder motor response to cholecystokinin.
Acromegaly↗
Hypergastrinaemia: a new mechanism.
The mechanism by which lack of gastric acid causes hypergastrinaemia was investigated in seven patients with pernicious anaemia. Perfusion of gastric juice from the fasting patients (adjusted to pH 7.0) into the stomachs of conscious rats caused a significant rise in plasma gastrin (median 14 [range 2-20] pmol/l to 27 [12-65] pmol/l; p less than 0.01), whereas perfusion of bicarbonate buffer (18 [13-23] pmol/l to 20 [9-25] pmol/l) or gastric juice from a duodenal ulcer patient (also pH 7.0; 13 [3-30] pmol/l to 17 [9-27] pmol/l) had no significant effect. During gastric lavage at pH 7.0 the median plasma gastrin concentration of the pernicious anaemia patients fell from 320 (63-1760) pmol/l to 125 (46-760) pmol/l (p less than 0.03).
Aged↗
Accelerated in vitro degradation of CCK-58 in blood and plasma of patients with acute pancreatitis.
Proteases released into the circulation during acute pancreatitis may hydrolyse circulating peptide hormones leading to altered regulatory functions. Cholecystokinin is a major regulator of postprandial gut function; stimulating pancreatic enzyme secretion, gallbladder contraction and diminishing food intake. Cholecystokinin-58 is the largest and most abundant form of this hormone in acid extracts of human intestine, and major amounts are released into the circulation after feeding. In order to test whether cholecystokinin-58 is degraded more rapidly due to the increased circulating of enzymes, this peptide was added to blood and plasma of patients with acute pancreatitis and incubated for various time intervals. The in vitro half life of cholecystokinin-58 was 10 +/- 1 minutes (mean +/- SE) in plasma and 11 +/- 1 min in blood from patients with acute pancreatitis, about four fold lower than the half life in plasma of healthy volunteers; 45 +/- 5 min. Degradation of cholecystokinin-58 produced immunoreactive forms of cholecystokinin that eluted in the positions of cholecystokinin-8 and cholecystokinin-33/39. We conclude that acute pancreatitis increases the degradation of CCK molecules.
Acute Disease↗
Tropic role of enteroglucagon in pancreatic adaptation to subtotal enterectomy.
Proximal small bowel resection causes pancreatic hyperplasia, presumably via a humoral mechanism. Although cholecystokinin can stimulate pancreatic growth, its proximal distribution in the gut makes it an unlikely intermediary after proximal small bowel resection. The potential roles of neurotensin and enteroglucagon were studied, since these hormones are mainly secreted from the ileum and proximal colon. Male Wistar rats (n = 50) weighing 200-250 g were randomized to receive 90 per cent proximal small bowel resection or jejunal transection and resuture (control). Rats were killed at 1 week or 1 month, when plasma was obtained for hormone assay and the pancreas was excised for protein and nucleic acid measurement. Proximal small bowel resection increased circulating enteroglucagon levels by 150 per cent at 1 week (P less than 0.002) and by 83 per cent at 1 month (P less than 0.005); neurotensin levels were unchanged. Pancreatic wet weight was 21 per cent greater 1 month after proximal small bowel resection (P less than 0.001). Proximal small bowel resection increased protein, RNA and DNA contents of the pancreas both at 1 week and at 1 month. Since plasma enteroglucagon correlated with these indices of pancreatic mass, enteroglucagon may have a pancreatotropic role (in addition to its enterotropic role).
Adaptation, Physiological↗
Achlorhydria-induced hypergastrinaemia: the role of bacteria.
1. Studies of Helicobacter pylori show that microbes can alter gastrin release. Lack of gastric acid (achlorhydria) causes hypergastrinaemia and allows bacteria to grow within the stomach. We speculated that the bacteria contribute to the rise in gastrin seen after acid inhibition, and tested the idea by comparing plasma gastrin levels during inhibition of acid secretion between germ-free and conventional rats. 2. Matched germ-free and conventional rats (n = 8 per group) received either vehicle (saline) or one of two doses of the histamine-H2-receptor antagonist loxtidine for 1 week. Gastrin was measured in cardiac blood by a specific r.i.a. 3. Plasma gastrin concentrations in germ-free and conventional rats were 59 +/- 11 pmol/l (mean +/- SEM) and 36 +/- 8 pmol/l, respectively, after vehicle, and 153 +/- 30 pmol/l and 181 +/- 27 pmol/l, respectively, after loxtidine at a dose of 10 mg day -1 kg -1, which partially inhibits acid secretion. Administration of loxtidine at a dose of 70 mg day -1 kg-1, which completely inhibits acid secretion, did not produce a significant extra rise in plasma gastrin concentration in germ-free rats (178 +/- 11 pmol/l), but further elevated plasma gastrin concentrations to 278 +/- 26 pmol/l in conventional rats (P less than 0.005 compared with germ-free rats). 4. Loxtidine produced a dose-dependent rise in the number of eosinophils in the gastric mucosa of conventional rats. 5. We conclude that partial inhibition of gastric acid secretion increases gastrin release independently of bacteria, but that bacteria are involved in the further rise in gastrin which occurs on more profound inhibition of gastric acid secretion.
Achlorhydria↗
Rhabdomyolysis after intramuscular iron-dextran in malabsorption.
The case of a 59 year old white man who had chronic malabsorption and selective IgA deficiency with severe iron deficiency is reported. In addition, he was deficient in vitamin E and selenium, important antioxidants which protect against lipid peroxidation. He was intolerant of oral iron and when treated with iron-dextran developed symptoms suggestive of polymyositis with evidence of rhabdomyolysis. It is suggested that free iron within iron-dextran activated free radicals, initiating lipid peroxidation and leading to polymyositis, rhabdomyolysis, and myoglobulinuria.
Anemia, Hypochromic↗
Postprandial hypergastrinaemia in patients with colorectal cancer.
Gastrin is trophic to colon cancers that possess gastrin receptors. Whether fasting serum gastrin concentrations are high in patients with colon cancer is controversial. We therefore studied the effect of food on serum gastrin concentrations in patients with colon cancer and control subjects. Fasting serum gastrin was greater, though not significantly so, in patients with colon cancer before surgery (mean (SD) 17.4 (3.6) pmol/l, n = 16) compared with control subjects (12.6 (1.9) pmol/l, n = 14). Postprandial increases in serum gastrin were significantly and persistently higher than normal in the cancer patients. These increases were due to a subset of six patients with serum gastrin concentrations greater than the control mean + 2 SD at 20 and 40 minutes (62 pmol/l-146 pmol/l). Four of the six patients had intra-abdominal metastases. The extent of the increase may well correlate with that of the disease. Surgical resection of the tumour resulted in a fall in serum gastrin values and probably reflects the cause of the hypergastrinaemia. Hypergastrinaemia may, therefore, be an important aetiological factor in colon carcinogenesis.
Abdominal Neoplasms↗
Gastric output of pancreatic secretory trypsin inhibitor is increased by misoprostol.
Pancreatic secretory trypsin inhibitor (PSTI) is a potent protease inhibitor that also has growth promoting activity. It has recently been identified in the foveolar cells of the stomach, which secrete mucus. We examined the effects of the prostaglandin E1 analogue misoprostol on gastric PSTI output. Seven normal volunteers took part. An initial period of gastric aspiration was followed by four 40 minute periods of gastric perfusion at 5 ml/minute of: 0.14 mol/l saline, 0.17 mmol/l bicarbonate, bicarbonate with misoprostol 400 micrograms, and then bicarbonate again. All perfusates contained polyethylene glycol 4000 as a marker. Misoprostol increased median gastric secretion of PSTI from 11 to 33 micrograms/hour (p less than 0.05), producing concentrations in gastric juice six times higher than those found in jejunal juice and about 1/30 of the values seen in pancreatic juice. Median mucus secretion increased to a lesser extent from 29 to 38 mg/hour during misoprostol. There was no change in intragastric concentrations of protein or of epidermal growth factor during infusion of misoprostol. Infusion of pentagastrin (6 micrograms/kg/hour) had no effect on gastric secretion of mucus, PSTI, or protein. Human gastric mucus was degraded on incubation with trypsin in vitro and this was prevented by the addition of PSTI. These results suggest that gastric PSTI may protect the gastric mucus layer against refluxed pancreatic proteases. Increased output of PSTI during microprostol may contribute to the protective effect of this drug.
Adult↗
'Low sodium' diuresis and ileal loss in patients with ileostomies: effect of desmopressin.
Patients with ileostomies show an early diuresis when sodium restricted; this, together with an obligatory ileal sodium loss, predisposes them to severe salt and water depletion. The role of arginine vasopressin in this circumstance and whether it is natriuretic, or antinatriuretic, is unclear. There is also controversy over its likely effect on small bowel fluid reabsorption. We have examined the effect of the non-pressor (V2) synthetic vasopressin analogue 1-deamino-8-D-arginine (desmopressin) on renal and ileal sodium and water excretion in ileostomy patients during acute adaptation to a low sodium diet. Patients were studied on two separate occasions (nonrandomised) with and without the administration of desmopressin (0.75 micrograms intramuscular, three times a day). In eight subjects without desmopressin there was pronounced diuresis on the first low sodium day, associated with a fall in renal sodium excretion and no change in ileal output or composition. In five (of the original) subjects with desmopressin there was pronounced antidiuresis, no change in renal sodium excretion, and no change in ileal output or composition. In both studies rises in plasma renin activity and salivary aldosterone concentration lagged behind the early decline in renal sodium excretion. We have confirmed the phenomenon of 'low sodium' diuresis after sodium restriction in ileostomy patients and shown that it can be prevented by desmopressin. Desmopressin has no direct or indirect effect on renal sodium excretion or ileal fluid and electrolyte loss in humans.
Aged↗
Inhibitory effect of a cholecystokinin antagonist on the proliferative response of the pancreas to pancreatobiliary diversion.
Since pancreatobiliary diversion probably stimulates pancreatic growth by increasing cholecystokinin secretion, the effect of the cholecystokinin antagonist CR-1409 on this adaptive response was tested. Male Wistar rats (n = 108) weighing 220-250g were randomised to receive either pancreatobiliary diversion (n = 60) or sham diversion (n = 48) and thereafter to receive either saline injections or CR-1409 (10 mg/kg/day, subcutaneously). Rats were killed at four, seven, and 14 days postoperatively, when blood was obtained for cholecystokinin assay and the pancreas was assessed for proliferative activity by three techniques: nucleic acid and protein assay, bromodeoxyuridine labelling, and metaphase arrest after vincristine administration (1 mg/kg, intraperitoneally). Pancreatobiliary diversion increased plasma cholecystokinin concentrations by 91% at seven days and 137% at 14 days, irrespective of CR-1409 treatment. Total pancreatic RNA content was doubled by pancreatobiliary diversion at four days (2.15 v 1.07 mg/100 g body weight: p less than 0.001) and at seven days (3.43 v 1.76 mg/100 g: p less than 0.001), and trebled at 14 days (4.27 v 1.32 mg/100 g: p less than 0.001). Pancreatobiliary diversion increased bromodeoxyuridine labelling index from 1.1 to 3.7% at seven days and the cell birth rate from 0.09 to 0.06%. CR-1409 completely abolished this proliferative response and partly prevented the rise in RNA. The results confirm pancreatic hypertrophy and increased acinar cell proliferation after pancreatobiliary diversion. CR-1409 prevents this adaptive growth, probably by blocking cholecystokinin receptors. Bromodeoxyuridine labelling and the metaphase arrest technique may be used to assess pancreatic cell kinetics.
Adaptation, Physiological↗
Dose-dependent effects of fentanyl on indomethacin-induced gastric damage.
Whilst developing a rat model for studies of gastric protection, we noticed that the anaesthetic agent 'Hypnorm', containing the opiate fentanyl 0.315 mg/ml and the butyrophenone fluanisone 10 mg/ml, was itself protective against indomethacin-induced damage: unrestrained animals given indomethacin (20 mg/kg) subcutaneously had an ulcer score of 9 +/- 1 mm2, compared with 1 +/- 1 mm2 in animals pre-treated with Hypnorm (0.8 ml/kg) and then given indomethacin (p less than 0.01). Further investigation showed this effect to be due to fentanyl-inhibiting gastric acid secretion: doses of fentanyl (90 and 180 micrograms/kg) which decreased indomethacin-induced damage also caused a rise in intragastric pH from 2.7 +/- 0.6 in controls to 5.1 +/- 0.8 and 5.0 +/- 0.8, respectively. However, the response of fentanyl varied depending on the dose given: fentanyl, 3.6 micrograms/kg did not affect indomethacin-induced damage, 8 +/- 2 vs. 9 +/- 1 mm2; fentanyl, 18 micrograms/kg potentiated damage, 15 +/- 4 mm2 (p less than 0.05), whereas fentanyl, 90 micrograms/kg and 180 micrograms/kg decreased damage, 2 +/- 1 mm2 and 0.1 +/- 0.1 mm2, respectively (p less than 0.01). Neither the butyrophenone haloperidol (8.3 mg/kg) nor the alpha-adrenergic receptor antagonist phenoxybenzamine (3 mg/kg) protected against indomethacin-induced damage. We conclude that fentanyl affects intragastric pH and can both potentiate and protect against indomethacin-induced damage. Furthermore, the potentiation of gastric damage by fentanyl occurred at doses similar to those used for human anesthesia, so clinical studies are suggested.
Animals↗
Interactions of pancreatic secretory trypsin inhibitor in small intestinal juice: its hydrolysis and protection by intraluminal factors.
It has been proposed that modulation of cholecystokinin (CCK) release by proteinases, proteinase inhibitors and protein is mediated by a pancreatic secretory trypsin inhibitor (PSTI), also called monitor peptide, in the rat. When human [125I]-PSTI was incubated with fasting small bowel juice or activated pancreatic juice greater than 88% of tracer eluted from gel chromatography in the characteristic position of hydrolysed PSTI. However, when the small bowel juice had been pre-incubated with soybean trypsin inhibitor 3 g/l, casein 5 g/l or lactalbumin 30 g/l, the hydrolysis of PSTI diminished so that 95%, 32%, and 33% respectively, now eluted in the characteristic position of free (i.e. intact and not bound to an enzyme) PSTI. When [125I]-PSTI was incubated with pure trypsin, chymotrypsin, elastase or enterokinase greater than 95% of tracer eluted in the position of PSTI-enzyme complex. Incubation of PSTI with trypsin plus one other enzyme was required to produce hydrolysis. The degree of protection of PSTI from hydrolysis in duodenal juice produced by these substances correlates with their affects on CCK release. Our findings support the hypothesis that PSTIs mediate the modulation of CCK release by intraluminal proteinases, proteinase inhibitors and proteins.
Body Fluids↗