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Biomedical subjects

P M Kleveland

Publications and source records attributed to P M Kleveland.

At least 37 records · Page 2Linked to original sources
PubMed1991

The gastrin receptor assay.

Gastrin is a major physiologic regulator of gastric acid secretion and growth of the oxyntic mucosa. Biologically active radiolabelled hormones may be used to characterize and localize receptors for peptide hormones. The cellular localization of the gastrin receptor in the fundic mucosa, however, is still a matter of great debate owing to difficulties in developing a gastrin receptor binding assay. Despite considerable work in several laboratories, the criteria for true receptor binding have not yet been fulfilled. The preparation of a suitable tissue receptor material (plasma membranes or isolated cells) from the heterocellular fundic mucosa seems to be the major problem. This problem may be related to the fact that the receptors are only present on the enterochromaffin-like cells (ECL), which constitute but a minor fraction of the cells in the oxyntic mucosa. Furthermore, the second messenger of gastrin is still not known, and the poor functional responsiveness of isolated cells and the oxyntic glands to gastrin further complicates the evaluation of the gastrin receptor. In this review the different steps in the gastrin receptor assay (the labelling of gastrin, preparation of the receptor, and the incubation and correlation of the binding and biologic effect of gastrin) are discussed.

Animals↗
PubMed1990

The predictive value of history in dyspepsia.

Symptomatic patients referred to an open-access upper gastrointestinal endoscopy completed a detailed, self-administered questionnaire aimed at assessing the predictive value of history in dyspepsia. Nine hundred and thirty patients were suitable for analysis. Of these, 29% were found to have organic dyspepsia. A substantial overlap of symptoms and demographic data was found among the various endoscopic diagnoses. Discriminating variables were identified by stepwise logistic regression analysis and included in predictive score models. Pain relieved by antacids, age above 40 years, previous peptic ulcer disease, male sex, symptoms provoked by berries, and night pain relieved by antacids and food were found to predict organic dyspepsia with a sensitivity and specificity of approximately 70%, when applied on the observed material. Similar probabilities were found for score models of peptic ulcer and esophagitis. In general, the low prevalence of organic diseases resulted in low positive and high negative predictive values. Accordingly, the main impact of the predictive models may be to reduce the number of negative endoscopies rather than to predict a precise diagnosis. Independent of disease category and age, 41% of the subjects expressed a fear of malignancy, emphasizing the value of reassurance from a negative endoscopy.

Adult↗
PubMed1990

The benefit of colonoscopy.

In a prospective study involving 833 consecutive outpatient and open-access colonoscopies, attempts were made to characterize the benefit of colonoscopy in terms of both predicted and unpredicted findings and therapeutic procedures. The endoscopist therefore predicted the endoscopic findings before the endoscopy. The results were compared for the different indications for colonoscopy. The overall agreement between the predictions and the colonoscopic findings was 61%. Clinically significant abnormalities were found in about half the examinations. The most frequent abnormal findings were benign polyps (24%), inflammatory bowel disease (17%), and malignancy (5%). In about half the patients with a malignancy the indication for colonoscopy was rectal bleeding, and half of the malignancies were not predicted. The greatest benefit of colonoscopy was found in patients referred because of overt rectal bleeding or occult faecal blood, and abnormal barium enema or endoscopy findings. The importance of complete colonoscopy in connection with operation for colorectal carcinoma is emphasized.

Colonic Polyps↗
PubMed1990

Effect of pancreatic enzymes in non-ulcer dyspepsia. A pilot study.

The symptomatic effect of pancreatic enzymes was examined in 37 patients with non-ulcer dyspepsia (NUD) recruited from general practice by means of a 24-day multicrossover model (MCOM) including six treatment periods and five regular interchanges between pancreatic enzymes and placebo. The evaluation was based on a comparison of the enzyme- and placebo-associated symptoms and on the number of times pancreatic enzymes were associated with less symptoms than the preceding or following placebo period in individual patients. No evidence of a short-term effect of pancreatic enzymes in NUD was found.

Adult↗
PubMed1989

[Idiopathic hypereosinophilic syndrome. Enterocolitis--a rare manifestation].

We describe a 44 year old male with severe enterocolitis as the dominating symptom of idiopatic hypereosinophilic syndrome. The clinical picture was dominated by incapacitating diarrhoea and abdominal cramps. A significant rise of eosinophils was found in peripheral blood. The patient was treated successfully using a combined regimen with hydroxyurea/steroids. We outline diagnosis, differential diagnosis and guidelines for treatment.

Adolescent↗
PubMed1989

Histamine and gastrin in plasma of patients with upper gastrointestinal diseases.

The etiology of peptic ulcer disease is completely unknown. However, gastric acid secretion plays an important role in the pathogenesis of the disease. Acetylcholine, gastrin and histamine are recognized as the main stimulators of the acid secretion. Extensive studies on blood gastrin have not incriminated this hormone in the pathogenesis of the disease. The present study was done to evaluate the role of circulating histamine in peptic ulcer disease using a sensitive and specific radioimmunoassay method. Since gastrin at least in some species seems to exert its stimulatory effect by releasing histamine, serum gastrin was also determined. There was no significant difference in plasma histamine between patients with duodenal or gastric ulcer, nonulcer dyspepsia or ulcer patients after proximal gastric vagotomy. However, patients taking a histamine-2 blocker (cimetidine or ranitidine) had significantly higher plasma histamine than those not taking these drugs. This effect was not due to interference in the histamine assay. There was no correlation between plasma histamine and plasma gastrin. Plasma gastrin was significantly increased in patients having been operated on with a proximal gastric vagotomy. In conclusion, plasma histamine is similar in patients with different upper gastrointestinal disorders. However, histamine-2 blockers may increase plasma histamine.

Blood Specimen Collection↗
PubMed1988

Muscarinic M2 stimulation releases histamine in the totally isolated, vascularly perfused rat stomach.

The present study examines the role of histamine in the stimulation of acid secretion induced by vagal nerve stimulation and by the muscarinic M1 agonist McN-A-343 in the totally isolated, vascularly perfused rat stomach. The stimuli were combined with an agent stimulating the cAMP system (isobutyl methylxanthine (IMX) or forskolin), a muscarinic antagonist (atropine or pirenzepine), or a histamine H2 antagonist (ranitidine). IMX and forskolin potentiated McN-A-343-stimulated acid secretion, yielding acid outputs of 280% and 260% of the sum of McN-A-343- and IMX-, or McN-A-343- and forskolin-stimulated outputs, respectively. Ranitidine inhibited acid secretion stimulated by McN-A-343 alone or in combination with IMX, whereas the forskolin-stimulated secretion was not influenced by the H2 antagonist. This strongly indicates that endogenous histamine potentiates muscarinic M1-stimulated acid secretion by increasing parietal cell cAMP. Vagal nerve stimulation with IMX increased acid output from 12.2 +/- 3.0 to 49.2 +/- 9.3 mumol/60 min (mean +/- SEM). The M1 antagonist pirenzepine and the M1/M2 antagonist atropine both significantly (p less than 0.01) inhibited vagally stimulated acid secretion. Histamine output as measured in the venous effluent was unchanged by McN-A-343, whereas nerve stimulation induced a clear increase in venous histamine output, from 101 +/- 21 before to 212 +/- 28 pmol/min (mean +/- SEM) after initiation of nerve stimulation. Histamine release was reduced to base-line levels by atropine but only insignificantly inhibited by pirenzepine, indicating a muscarinic M2 stimulation of histamine release in the rat stomach.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Cimetidine responders in non-ulcer dyspepsia.

The effect of cimetidine and placebo was examined in 123 patients with non-ulcer dyspepsia (NUD) by means of a 12-day multi-crossover model with 5 regular interchanges between cimetidine and placebo. The evaluation of effect in individual patients was based on the number of times cimetidine was associated with less symptoms than the preceding or following placebo period. If cimetidine had no effect, the probability of being defined as a cimetidine responder was 25%. In general, cimetidine was associated with less symptoms than placebo (p less than 0.0001). Forty patients were identified as cimetidine responders (R) and the remaining patients were termed non-responders (NR). Symptoms compatible with gastroesophageal reflux were significantly more frequent in R than in NR, whereas the opposite was true for symptoms of the irritable colon syndrome. The ability of symptoms selected by stepwise logistic regression to predict response to cimetidine showed at best a sensitivity of 75% and a specificity of about 65%. No differences were found between R and NR with regard to acid secretion, endoscopic and histologic findings, or the result of an acid perfusion test. The present study supports the existence of a subgroup of cimetidine responders among patients with NUD characterized by symptoms suggestive of gastroesophageal reflux disease in the absence of confirmatory objective evidence.

Adult↗
PubMed1988

Do we need to listen to the patient? The predictive value of symptoms.

We have previously shown that the endoscopist is able to predict the endoscopic diagnosis in about two thirds of the patients. We report some preliminary findings from two different studies on the ability of symptoms to predict endoscopic findings. Comparison with similar studies in Glasgow and Huddinge suggests that the predictive value of symptoms probably varies between countries and depends on the population dealt with as well as on the methods used for symptom evaluation. Predictive models for peptic ulcer or endoscopic esophagitis based on symptoms showed at best an about 60-70% sensitivity and specificity. We strongly feel that future studies on the predictive value of symptoms should be more focused on the first step in the decision process in general practice.

Esophagitis, Peptic↗
PubMed1987

The effect of secretin on acid and pepsin secretion and gastrin release in the totally isolated vascularly perfused rat stomach.

The effect of secretin on acid and pepsin secretion and gastrin release in the totally isolated vascularly perfused rat stomach was studied. With the phosphodiesterase inhibitor isobutyl methylxanthine (IMX) added to the vascular perfusate, baseline acid secretion was 4.7 +/- 1.1 (mean +/- S.E.M.) mumol/h and baseline pepsin output 1147 +/- 223 micrograms/h. Secretin significantly inhibited acid output to a minimum of 1.4 +/- 0.2 mumol/h at a concentration of 25 pM in the vascular perfusate (P less than 0.01). Pepsin output was not significantly different from baseline at any of the secretin doses tested. Threshold secretin concentration for acid inhibition was 5 pM. IMX stimulated gastrin output from 48 +/- 9 pM in the basal state to 95 +/- 13 pM after IMX (P less than 0.01). Secretin inhibited gastrin release only at the maximal dose of 625 pM, when gastrin concentration in the venous effluent decreased from 93 +/- 19 to 68 +/- 19 pM after secretin. Thus, in the totally isolated vascularly perfused rat stomach secretin in physiological concentrations inhibits acid secretion by a direct action on the acid secretory process and not via gastrin inhibition. The study also suggests that gastrin release at least in part is mediated via increased intracellular cAMP.

1-Methyl-3-isobutylxanthine↗
PubMed1987

The storage time of monoiodinated gastrin affects the biological activity and binding to rat fundic plasma membranes similarly, whereas the immunoreactivity is less affected.

Monoiodinated gastrin was produced by a gentle Iodo-gen method, followed by gel and ion-exchange chromatography. During storage this tracer has previously been found to retain its immunological activity, whereas its specific binding to rat gastric fundic plasma membranes decreased rapidly. To examine whether the loss of specific binding could be reflected in loss of biological activity, we examined the tracer at regular intervals for immunoreactivity by binding to an antibody directed against the C-terminal bioactive site of the gastrin molecule; for biological activity in the totally isolated, vascularly perfused rat stomach concomitantly stimulated with a phosphodiesterase inhibitor; for specific binding ('receptor binding') to a rat gastric fundic plasma membrane fraction; and for fragmentation and intramolecular changes by fast protein liquid chromatography (FPLC). Biological activity and 'specific' binding showed a parallel decrease to zero during 4 weeks of storage, whereas the immunoreactivity was retained much longer. There was no apparent fragmentation of the gastrin molecule during the 1st month after preparation as evaluated by FPLC. This study accordingly shows that both biological activity and specific binding to a gastric fundic plasma membrane fraction of 125I-gastrin are lost before detectable loss in immunoreactivity and before FPLC-detectable fragmentation of the molecule. Thus, during the early storage period subtle changes in the 125I-gastrin molecule must take place. Since the specific binding is so closely correlated to biological activity, it suggests that the binding actually represents true receptor binding.

Animals↗
PubMed1987

Pepsin secretion by the totally isolated, vascularly perfused rat stomach.

The gastric pepsin output by the totally isolated, vagally denervated, and both luminally and vascularly perfused rat stomach was studied. Basal release of pepsin was 3% of total gastric mucosal stores per hour. Topical (luminal) administration of 0.001 M HCl was without effect. Graded concentrations of pentagastrin, gastrin, histamine, and impromidine in the vascular perfusate were tested. Pentagastrin induced only a slight increase in pepsin release (15% of total content per hour). Gastrin had a more pronounced effect and elicited a significant increase in the pepsin output, reaching a maximum of 28% of total pepsin content per hour. The CD50 of gastrin was 0.061 nM. Histamine and impromidine likewise produced significant increases in the pepsin secretion (maximum, 40% and 35% of total stores per hour, respectively). When the CD50 of histamine (0.718 microM) was compared with that of impromidine (0.011 microM), impromidine on molar basis had 65 times higher potency than histamine as a pepsin secretagogue. When the pepsin and acid responses during gastrin, histamine, and impromidine stimulation were compared, the pepsinogen secretion was shifted to the left and thus was more sensitive to stimulation than the acid secretion.

Animals↗
PubMed1987

Gastrin produces an immediate and dose-dependent histamine release preceding acid secretion in the totally isolated, vascularly perfused rat stomach.

Increasing doses of gastrin 1-17 (G1-17) were administered to totally isolated, vascularly perfused rat stomachs prestimulated with the phosphodiesterase inhibitor isobutyl methylxanthine (IMX). Vascular and luminal histamine outputs and luminal acid output were monitored at short intervals. G1-17 induced an immediate histamine release to the vascular perfusate, preceding the increase in acid secretion by approximately 10 min. Vascular histamine output increased from a base line (IMX only) of 4.0 +/- 0.4 to a maximum of 34.5 +/- 7.3 nmol/60 min (mean +/- SEM) after 1040 pM G1-17, and acid output from 8.0 +/- 2.8 to 61.5 +/- 7.0 mumol/60 min after 520 pM G1-17. Acid output was correlated to vascular histamine release (r = 0.64, p less than 0.001). Gastrin produced a histamine release giving gastric venous concentrations of the same magnitude as the concentration of histamine necessary to induce a comparable acid response. Histamine release to the lumen, on the other hand, paralleled the acid secretion in time, suggesting it to be a passive phenomenon secondary to acid secretion. Thus, the present study for the first time shows that gastrin induces vascular histamine release of such a magnitude that this substance could be the mediator of the gastrin effect on acid secretion.

Animals↗
PubMed1987

Gastric acid secretion in the totally isolated, vascularly perfused rat stomach. A selective muscarinic-1 agent does, whereas gastrin does not, augment maximal histamine-stimulated acid secretion.

The gastric acid secretion in response to graded doses of gastrin, histamine, impromidine (a selective H2-receptor agonist), and the muscarinic-1 agonist McN-A-343 was studied in the totally isolated, vascularly perfused rat stomach. Combinations of stimulants at doses giving maximal acid secretion for each secretatogue were thereafter tested. All stimulants increased the gastric acid output significantly compared with the base-line output (7.2 +/- 2.0 mu eq/h). Gastrin induced significant increases in acid outputs at very low and physiologically relevant concentrations with a threshold concentration of 65 pM. Nevertheless, maximal gastrin-stimulated acid secretion represented only 55% of the maximal histamine-stimulated acid output of 154.8 +/- 10.0 mu eq/h. Impromidine and McN-A-343 induced a maximum 59% and 34% of maximal histamine-stimulated acid output, respectively. Adding gastrin to the maximal histamine of impromidine-stimulated stomachs did not increase the acid secretion further. Histamine and McN-A-343 in combination, however, induced a more than additive increase in the gastric acid output (232.0 +/- 14.7 mu eq/h) than did histamine and McN-A-343 separately (154.8 +/- 10.0 and 53.0 +/- 6.7 mu eq/h, respectively). The results indicate that in the rat, gastrin stimulates the parietal cell indirectly via histamine release, whereas muscarinic agents (cholinergic stimulation) act directly via a separate receptor.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1987

Stimulated pepsin secretion after omeprazole-induced acid suppression in the totally isolated, vascularly perfused rat stomach.

The effect of the H2 agonist impromidine, gastrin 1-17 (G1-17), pentagastrin, and the M1 agonist McN-A-343 on pepsin secretion in the acid-inhibited totally isolated, vascularly perfused rat stomach was studied. Omeprazole produced a 97-98% inhibition of stimulated acid outputs. Base-line pepsin output after omeprazole was 712 +/- 278 micrograms/h (mean +/- SEM) and, after stimulation with impromidine, 1528 +/- 164 micrograms/h; G1-17, 1520 +/- 180 micrograms/h; and pentagastrin, 2063 +/- 605 micrograms/h. Output after McN-A-343 was 534 +/- 69 micrograms/h. Pepsin secretion after impromidine, G1-17, and pentagastrin was significantly (p less than 0.01) higher than base-line output. McN-A-343 had no significant effect on pepsin output in this model. Pepsin secretion after impromidine, G1-17, and pentagastrin was considerably lower than found in the same model with uninhibited acid output. This could be caused by decreased tubular 'washout' after acid inhibition, and, accordingly, no conclusions can be drawn as to the possible stimulatory effect of acid on pepsin secretion. However, the present study indicates that pepsin secretion can be stimulated directly by impromidine and (penta)gastrin without concomitant acidification of the gastric glands.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1987

Dyspepsia: Therapeutic response as a diagnostic tool.

Non-ulcer dyspepsia (NUD) is a poorly defined heterogenous condition less well suited for the conventional randomized and placebo controlled parallel type trials. We have designed a multi cross-over model (MCO-model) with the facility of providing information about drug responses in individual patients. A pilot study suggested that the model may identify individual cimetidine responders among patients with dyspepsia. Preliminary findings from an ongoing study in patients with NUD supports the existence of a subgroup of cimetidine responders characterized by gastroesophageal reflux symptoms and possibly an increased basal acid secretion.

Cimetidine↗
PubMed1986

Amylase, pancreatic isoamylase and lipase in serum before and after endoscopic pancreatography.

Serum amylase, isoamylase and lipase were determined in 17 patients with pancreatic or biliary diseases before and after endoscopic retrograde pancreatography (ERP). Within 1/2-2 hours after cannulation of the pancreatic duct, serum lipase was increased to approximately 4 times the upper reference level and normalized almost completely at 24 hours. A much smaller increase was found in amylase and isoamylase. The elevation in enzyme activities was less in patients with abnormal than with normal ERP. The results suggest that lipase is a more sensitive indicator of pancreatic injury than amylase and isoamylase.

Amylases↗