PubMed Health⌕ Search

Biomedical subjects

P M Kleveland

Publications and source records attributed to P M Kleveland.

53 records · Page 3Linked to original sources
PubMed1986

Bioassay of gastrin, using the totally isolated, vascularly perfused rat stomach. A biomodel sensitive to gastrin in physiological concentrations.

A bioassay sensitive to gastrin (G 1-17) in physiological concentrations and suitable for testing of biological activity of minor amounts of radioiodinated gastrin is reported. G 1-17 was iodinated by a gentle Iodo-gen method and purified to high specific activity (1900 Ci/mmol). Totally isolated vascularly perfused rat stomachs were prepared and stimulated by graded amounts of G 1-17. Gastrin 'dose'-dependently increased the acid output from 5.7 +/- 1.0 mueq/40 min (basal) to a maximum of 58.8 +/- 10.0 mueq/40 min at a concentration of 520 pmol/l in the vascular perfusate. The lowest G 1-17 concentration that significantly increased the acid output from the basal value was 65 pmol/l, corresponding to a dose of 17.5 ng/stomach-hour. 125I-G 1-17 also increased the acid output significantly at this threshold dose. The amount of lactic acid enzymatically determined in the luminal perfusate was negligible, indicating a true parietal cell stimulation. Accordingly, a very sensitive bioassay for gastrin, suitable for testing of biological activity of G 1-17 and 125I-G, is described. Significant acid responses were obtained with physiological concentrations of gastrin, requiring less than 100 ng of hormone and labelled hormone, respectively, to show biological activity.

Animals↗
PubMed1986

The effect of pentagastrin on the gastric secretion by the totally isolated vascularly perfused rat stomach.

Gastric acid and pepsin secretion by the totally isolated vascularly perfused rat stomach was studied. Rat stomachs were vascularly perfused with Krebs-Ringer buffer gassed with 96% O2-4% CO2 and containing 5 mM glucose, 5 mM pyruvate, 4% bovine serum albumin, 10% ovine erythrocytes, and various concentrations of pentagastrin. The gastric lumen was perfused with distilled water gassed with 100% O2. To remove preformed juice and to enable preformed pepsin to be washed out, the initial 20-min gastric juice was discarded. The gastric effluent was then collected continuously for six 10-min periods, and the H+ concentration was determined by titration and the pepsin concentration estimated by a hemoglobin digestion method. Inclusion of pentagastrin in the perfusion buffer increased the acid output dose-dependently from 2.3 +/- 0.4 mueq/h during the control perfusion to a maximum of 12.7 +/- 2.1 mueq/h (p less than 0.01). With the higher doses of pentagastrin and concomitant high acid secretion, gastric acid secretion faded during the collection period. In contrast, gastric pepsin secretion was virtually unaffected by pentagastrin. The present model should be useful for studying the regulation of gastric acid and pepsin secretion.

Animals↗
PubMed1986

Binding and degradation of 125I-gastrin by plasma membranes from homogenized rat gastric mucosa.

Binding of 125I-gastrin to the 270-30,000 g fraction from homogenized rat oxyntic mucosa was studied. 'Specific' binding was calculated by subtracting the binding at excess cold gastrin from the binding with labelled gastrin (250 pM) only. At 30 degrees C specific binding rose rapidly to a short-lived maximum before falling gradually, whereas at 15 degrees C and 0 degree C specific binding rose gradually to a higher plateau level. The reduced binding at 30 degrees C could be caused by degradation of either the tracer or the binding site or by a combination of these two events. Degradation of 125I-gastrin was evaluated by trichloroacetic acid (TCA) precipitation, fast protein liquid chromatography, and binding to a gastrin antibody (immunoreactivity). The effect of incubation on the binding site was evaluated by preincubation of the homogenate fraction before adding gastrin. In separate studies, the proteolytic activity of the homogenate fraction was studied by TCA precipitation of radioactive casein. Different enzyme inhibitors tested were virtually ineffective in preventing gastrin and casein degradation. Only lowering the incubation temperature to 15 degrees C or lower could prevent this degradation. The reduced and transient binding of 125I-gastrin at 30 degrees C most probably reflects tracer degradation. Accordingly, the gastrin binding experiments were performed at 15 degrees C. Only homogenates from the oxyntic area of the stomach bound 125I-gastrin specifically and with a Kd of 0.8 nM (Scatchard analysis). However, micromolar concentrations of unlabelled gastrin were required to inhibit half maximal binding of the tracer. The tracer binding was unaffected by secretin, slightly reduced by a CCK-9 analogue, and more markedly reduced by pentagastrin.

Animals↗
PubMed1986

Effect of pentagastrin on gastric acid secretion in the totally isolated vascularly perfused rat stomach stimulated with the phosphodiesterase inhibitor isobutyl methylxanthine.

The development of a very sensitive stomach biomodel, using the totally isolated rat stomach, is reported. Pentagastrin-stimulated acid secretion in anesthetized and conscious rats was also studied, and the capacity to produce acid and the sensitivity towards pentagastrin in the different rat stomach models were compared. The secretory capacity and the sensitivity were evaluated by means of the maximal acid output (MAO) and threshold dose (TD), respectively. Conscious rats provided with gastric fistulas had a MAO of 48 +/- 6.3 mu eq/10 min and a TD of 6 micrograms/kg-h. In anesthetized rats with luminally perfused stomach MAO was reduced to 11.6 +/- 1.2 mu eq/10 min, whereas the sensitivity was increased, as indicated by a TD of 0.5 micrograms/kg-h. Totally isolated vascularly perfused rat stomachs without isobutyl methylxanthine (IMX) produced even less acid (MAO, 2.2 +/- 0.4 mu eq/10 min) without any change in demand for stimulant (TD, 0.25 micrograms/stomach-h). Addition of IMX to the vascular perfusate in the isolated stomach preparation increased the MAO to 8.0 +/- 1.0 mu eq/10 min and induced a remarkable reduction in demand for stimulant, with a TD obtained already at a pentagastrin dose of 0.008 micrograms/stomach-h, corresponding to a concentration of pentagastrin in the vascular perfusate medium of 84.5 pM. Accordingly, the totally isolated vascularly perfused rat stomach stimulated with IMX is the most sensitive bioassay for (penta)gastrin so far reported.

1-Methyl-3-isobutylxanthine↗
PubMed1986

1- and 4-week cimetidine treatment for duodenal ulcer.

Forty-eight patients with symptomatic duodenal ulcer were randomized to 4 weeks' treatment with cimetidine, 1 g/day (C4), or 1 week of cimetidine treatment followed by 3 weeks of placebo (C1 + P). The study was performed double blind. The symptoms were recorded daily on a visual analogue scale. Endoscopy was performed after 4 weeks. Two patients receiving C1 + P dropped out during the 2nd week because of worsening symptoms. With the two dropouts being recorded as 'unhealed ulcers', the 4-week healing rates were 16 of 24 (67%) and 15 of 24 (63%), with C4 and C1 + P, respectively (p greater than 0.05). Even without including the two dropouts, the patients treated with C1 + P had significantly more symptoms during the 2nd and 3rd treatment week than those treated with C4. The present study indicates that 1 week of cimetidine treatment is not sufficient in patients with duodenal ulcer.

Cimetidine↗
PubMed1986

The clinical benefit of routine upper gastrointestinal endoscopy.

In a prospective study including 1526 consecutive endoscopies, attempts were made to characterize the benefit of upper gastrointestinal endoscopy. Before endoscopy judgements were made about the most likely diagnosis and treatment and about the degree of suspicion of upper gastrointestinal malignancy. After endoscopy the same types of judgement were made again. The study showed that about half of the endoscopies disclosed clinically significant abnormalities. Furthermore, about every third endoscopy led to unpredicted diagnostic and diagnostic and therapeutic consequences. The benefit was comparably small in patients below the age of 40 years and particularly great in patients above the age of 65, in patients submitted to endoscopy because of barium meal pathology or general suspicion of malignancy, and in patients with upper gastrointestinal bleeding. In general, the present study supports the widespread use of upper gastrointestinal endoscopy in clinical practice.

Adolescent↗
PubMed1985

The effect of cimetidine in non-ulcer dyspepsia. Experience with a multi-cross-over model.

The symptomatic effect of cimetidine was examined in 27 patients with non-ulcer dyspepsia (NUD) by means of a multi-cross-over model (MCO model) for testing the symptomatic effect of drugs in individual patients. None of the patients showed an ulcer at the time, but 20 patients had evidence of previous peptic ulcer disease. The variant of the MCO model used included six treatment periods and three regular interchanges between cimetidine and placebo. Treatment periods lasted 2 or 4 days. The individual results were evaluated on the basis of the number of times (X score) cimetidine was associated with less symptoms than the preceding or following placebo. In general, cimetidine was associated with significantly (p less than 0.02) less symptoms than placebo. The X-score distribution was therefore skew in favour of high scores. Five patients showed the maximal X score of 5. The chance of getting an X score of 5 when cimetidine is not better than placebo is about 9%. Accordingly, the risk of being wrong when defining these five patients as cimetidine responders is 9%. The present study confirms that the MCO model may identify individual cimetidine responders among patients with NUD.

Adult↗
PubMed1985

The preparation of bioactive 125I-gastrin, using Iodo-gen as oxidizing agent, and the use of this tracer in receptor studies.

The preparation of 125I-labelled gastrin 1-17, using Iodo-gen as oxidizing agent, is described. Mono-125I-gastrin was purified from the iodination mixture by gel chromatography, followed by ion-exchange chromatography. The Iodo-gen-labelled 125I-gastrin tracer showed a slightly higher immunoreactivity than a similarly purified tracer produced by a gentle chloramine-T method (50% binding of 0.45 fmol tracer at an antibody dilution of 945,000 versus 780,000, respectively). The Iodo-gen-labelled 125I-gastrin, which had the same biological activity as native gastrin when tested in conscious gastric fistula rats, was tested for specific binding at 30 degrees C in pronase-isolated rat gastric fundic cells and plasma membranes from the same area. A specific binding with a Kd of 4.5 X 10(-9) M was found to isolated fundic cells. This binding was rapid and reached equilibrium within 40 min. The dissociation induced by a 10-fold dilution of the incubation medium was biphasic, with a rapid initial phase and a slow late phase, indicating two different binding sites. On the other hand, no reproducible specific binding of the tracer to plasma membranes was obtained. This study shows that Iodo-gen is suitable as an oxidizing agent in iodination of gastrin without loss of biological activity. The tracer produced may be used in receptor studies for isolated cells, whereas the use of plasma membranes for studying gastrin receptors needs reevaluation.

Animals↗
PubMed1985

Clinical significance of upper abdominal symptoms.

Upper abdominal symptoms are frequent in the healthy population. The clinical significance of upper abdominal symptoms appears to be slight when evaluated singly but more satisfactory when taken together. There is an urgent need for an improved data base of information with regard to the relationship between upper abdominal symptoms and disease.

Abdomen↗
PubMed1985

Controlled trials in gastrodyspepsia: a methodological aspect.

Non-ulcer dyspepsia (NUD) is a poorly defined condition that is not very suitable for conventional randomised double-blind studies. A multi cross-over model (MCO-model) has been designed allowing identification of individual drug responders with a defined degree of certainty. The model involves regular interchanges between periods with active drug and placebo, and the evaluation is based on the number of times the active drug is associated with fewer symptoms than the preceding or following placebo period (X-score). A drug responder may be defined by a certain minimum value for the X-score. The risk of being wrong may then be easily calculated from the probability distribution of the X-score. The effect of cimetidine in patients with NUD has been studied using a variant of the MCO-model including 6 treatment periods of 2 or 4 days' duration. So far, the conclusion that the MCO-model is able to identify individual cimetidine responders among patients with NUD appears to be justified. The preliminary findings furthermore suggest that cimetidine responders among patients with NUD are characterised rather by symptoms suggestive of reflux esophagitis than by hypersecretion of acid.

Cimetidine↗
PubMedDate not supplied

Gastrin-physiological and pathophysiological role: clinical consequences.

Gastrin plays a central role in the regulation of acid secretion. It is released by meals in quantities sufficient to explain meal-stimulated acid secretion. Gastrin stimulates acid secretion mainly by releasing histamine from the enterochromaffin-like (ECL) cell. Whether gastrin has any functional direct effect on the parietal cell remains to be shown. Gastrin stimulates not only the function but also the growth of the ECL cell, and long-term hypergastrinemia may lead to ECL cell carcinoids. The role of the ECL cell in human gastric carcinogenesis is controversial, but it seems wise to avoid long-term iatrogen hypergastrinemia especially in young persons. Interestingly, the oxyntic mucosal D cell, on which gastrin has a negative trophic effect, may play a role in gastric stump carcinoma, and thus hypogastrinemia may also dispose to gastric cancer.

Enterochromaffin Cells↗