Surgery or cimetidine? I. Comparison of two plans of treatment: operation or repeated cimetidine.
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Biomedical subjects
Publications and source records attributed to D Andersen.
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Prepyloric (PPU), pyloric (PU), and duodenal bulb ulcers (DU) are traditionally incorporated in the clinical entity 'duodenal ulcer disease'. Clinical and gastric secretory data were analyzed with respect to the ulcer location in a prospective study with complete data from 776 patients. 574 had DU, and the female/male ratio was 0.39. 95 had PU (female/male ratio = 0.61) and 107 PPU (female/male ratio = 0.53). The higher female/male ratio for PU and PPU as compared to DU was significant. The age distribution showed a significant trend to younger age representation of males in the DU group, while the age distribution of the females was equal for the three groups. The duration of symptoms before elective surgery was equal for all three groups. The pentagastrin-stimulated peak acid output was significantly higher for DU compared to PPU, and this applied for both sexes even when the values were corrected for body weight as well as for age differences. Our results indicate DU and PPU to be materially different while PU constitute an intermediary group.
Because of the central role of blood platelets in haemostasis, 111In-labelled platelets might be supposed to participate in the haemostatic process and give rise to scintigraphic hot spots at the bleeding sites in cases of intermittent gastrointestinal haemorrhage. Three patients with intermittent gastrointestinal haemorrhage are described in whom focal tracer accumulations after injection of autologous 111In-labelled platelets indicated the presence of transient gastrointestinal haemorrhage. Repeatedly performed scintigraphy after injection of 111In-labelled platelets may prove to be a useful tool for the localization of intermittent gastrointestinal haemorrhage.
Changes in gastric acid secretion during the 1st year after selective gastric (SGV) and parietal cell (PCV) vagotomy for duodenal ulcer disease were studied. Pentagastrin tests were performed preoperatively and 3 months and 1 year after surgery in 383 SGV and 302 PCV patients. Resting juice pH showed after both operations a trend towards the preoperative distribution from 3 months to 1 year. Basal acid output showed a similar pattern. The initial reduction in pentagastrin-stimulated peak acid output (PAOpg) was most pronounced after SGV, but an increase occurred for both operations during the 1st postoperative year. An exception from this was the minority of patients who had a less than 20% initial reduction. They had a further decrease in their PAOpg. No sex difference and no influence of the duration of symptoms could be demonstrated. The patients with less than 20% initial reduction were younger than the other groups, and this applied for both SGV and PCV. The patterns of change in gastric acid secretion during the first year after vagotomy suggest that biologic factors are active, in addition to the effect of the surgical technique.
Clinical and secretory data were analysed with respect to the recurrence rate for 685 patients treated with either selective gastric vagotomy (SGV) or parietal cell vagotomy (PCV) for duodenal ulcer disease. The duration of ulcer history before surgery was of no importance for the recurrence risk. Men with recurrence after SGV were significantly younger than men without recurrence, but no difference was found for women with SGV or for men and women with PCV. The recurrence rate was not higher for hypersecretors (pentagastrin-stimulated peak acid output (PAOpg) greater than 45 mmol/h) than for patients with lower PAOpg. Resting, basal, and stimulated secretion 3 months after surgery were higher for the patients with recurrence than for the patients without, but only a few of the secretion values were significantly different. A higher recurrence rate was found for the patients with the lowest initial acid reduction, and this trend was more pronounced in the PCV group. With regard to the change in gastric secretion during the first year after vagotomy a significant rise was seen for the PCV patients who developed recurrence in spite of initial reduction of more than 60%. For all SGV patients and the PCV patients with an initial reduction on the average or less, the change in secretion capacity had no influence on the recurrence rate. The findings are in accordance with reports about anatomical limitations for a sufficient PCV in about 20% of the patients.
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The purpose of this study was to elucidate the effect of intravenously administered dopamine on dopamine receptors and adrenergic receptors in terms of its effect on gastric acid secretion, the kinetic mechanism, blood flow, and antral motility. Dopamine was used alone and in conjunction with selective blockade of alpha-, beta-, and dopaminergic receptors. A significant inhibition of gastric acid secretion was found with the highest dose of dopamine used (40 micrograms/kg/min). The kinetic study showed characteristics of a non-competitive type. The anti-secretory effect dopamine was significantly blocked by non-selective beta-blockade or by selective beta-blockade but not by alpha- or dopaminergic receptor blockade. This suggests that the inhibitory effect of dopamine on gastric secretion is mediated by beta-receptors. There was no significant effect on gastric mucosal blood flow, but the ratio between blood flow and acid secretion was significantly elevated during dopamine infusion, indicating that the acid inhibition was not secondary to changes in blood flow. It is concluded that the dopamine inhibition of acid secretion is mediated by beta 1-receptors, unlike the effect on antral gastric motility, which is mediated by dopamine receptors.
The purpose of the present study was to evaluate the effect of dopamine on gastric antral motility in conscious dogs with gastric fistula by using miniature strain-gauge transducers. Infusion of pentagastrin changed the contractile activity to a digestive state. Dopamine, an endogenous catecholamine, was used alone and in conjunction with selective blockade or adrenergic and dopaminergic receptors. The stimulated antral motility was inhibited by dopamine. The effect was significantly blocked by the peripherally acting dopaminergic blocker domperidone and by cis-flupenthixol, which blocks both peripheral and central dopaminergic receptors. The effect of dopamine was not significantly altered by the beta 1-adrenoceptor blocker practolol, the alpha-adrenoceptor blocker phentolamine, or the alpha + beta-adrenoceptor blocker labetalol. Consequently, this study indicates that dopamine acts on gastric antral motility through dopaminergic receptors. beta-Adrenergic receptors, which are active in the impairment of gastric acid secretion, seem not to be involved in the motility response.
The influence of sham feeding (PAOSh) preceding pentagastrin-stimulated gastric acid secretion (PAOPg) was investigated in 28 patients with duodenal ulcer (DU) before vagotomy and in 36 after parietal cell vagotomy (PCV). Sham feeding had little influence on PAOPg, and it is concluded that the two secretion tests may be combined. The ratio PAOSh/PAOPg was significantly reduced by PCV. Fourty-four patients with DU were studied for 1 year after PCV, and their PAOPg was measured preoperatively and their PAOPg and PAOSh postoperatively. Seven of the 44 patients had recurrent ulcer within 1 year. PAOPg had no predictive value pre- and post-operatively, but postoperative PAOSh and PAOSh/PAOPg were both significantly higher in patients with recurrent ulcer. It is concluded that PAOSh and PAOSh/PAOPg after PCV may assess completeness of vagotomy, but the relationship between PAOSh and risk of recurrent ulcer may be stronger than that between PAOSh/PAOPg and recurrence.
Measurements of total rat testicular protein carboxyl-methylase (PCM) activity at various ages ranging from 10 to 90 days showed a rapid (fivefold) increase between 20 and 30 days, coincident with the occurrence of haploid germ cells. When partially purified testicular enzyme, at different ages, was fractionated by isoelectric focusing, the activity of the individual PCM isomers displayed clear differences in the time at which maximal activity was reached. The most acid PCM isoenzyme (pI 6.1) was the dominant isoform in the immature testis and exhibited the highest increase in activity between 20 and 30 days of age. During the same age interval, the activity of the other two isoenzymes (pI 6.7 and 7.4) increased only slightly. At 50 days, while the isofocusing profile revealed no additional increase in the activity of the acid isoform (pI 6.1) and only a doubling in the activity of the second isomer (pI 6.7), the most basic isoenzyme displayed a drastic increment in specific activity (approximately sixfold when compared to 30 days). This indicates that the PCM isozymes have different cellular localization in the seminiferous tubules. The acid isomer (pI 6.1) appears to be associated to the early stages of spermatogenesis and may represent both germ cell and somatic cell PCM. The basic isomer (pI 7.4) may be specific for germ cells (spermatids), and is most likely associated with the later stages of germ cell maturation.
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This paper reports some physico-chemical properties of the Mn+-dependent adenylate cyclase (AC) of the rat testis. The AC activity in the crude cytosol (106 000 x g) migrates as a single peak in a linear sucrose gradient (5--20%) with a sedimentation coefficient (S20,w) of 4,1. The enzyme exhibits an Einstein-Stokes radius (rs) of 30.6 A as assessed by gel filtration (Kav = 0.50) on a calibrated Sephadex G-200 column. The molecular shape is close to spherical (f/f0 = 1.25). Isoelectric focussing of the AC peak (Kav = 0.50) from the Sephadex G-200 column revealed a pI of 5.7. Ion exchange chromatography of the crude cytosol on a Whatman DE-52 column gave a single peak eluting between 0.13--0.17 M NaCl. Electrophoresis on polyacrylamide gels resulted in a migrating AC peak with an apparent Rf of 0.40 relative to bromophenol blue. The Mn2+-dependent AC is not retained on a Con-A Sepharose 4B column indicating that the enzyme molecule does not contain sugars possessing alpha-D-manno- or alpha-D-glucopyranosyl terminal groups. (NH4)2SO4 precipitates the AC activity (4 degrees C) between 30--60% saturation. The yield approximates 85% of total AC activity with the specific activity reaching a plateau (110 pmoles cAMP/mg protein/min.) at 50% saturated (NH4)2SO4. The soluble Mn+-dependent AC of the rat testis thus appears to be relatively symmetrical with a size of approximately 52 000 D and a negative charge at physiological pH. Apparently it does not contain sugar moieties and it exhibits little molecular heterogeneity.
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The purpose of this study was to elucidate the effect of a beta 1-adrenoceptor agonist on gastric acid secretion in conscious dogs with gastric fistula. Isoprenaline, a beta 1- and beta 2-agonist was used alone and in conjunction with selective blockade of beta 2- and beta 1-receptors. Isoprenaline dose-dependently inhibited the secretory volume and the acidity. The antisecretory effect of isoprenaline was significantly blocked by the beta 1-adrenoceptor blocker practolol and by the beta 1 + beta 2-adrenoceptor blocker propranolol but not by H 35/25, a beta 2-adrenoceptor blocker. This indicates that isoprenaline acts on the acid secretion exclusively through beta 1-receptors. Dose-response experiments with five logarithmically increased doses of pentagastrin and one dose of isoprenaline showed unchanged calculated maximum response and an increase in half-maximum acid response. It is concluded that the inhibitory effect of isoprenaline on gastric acid secretion is of competitive or uncompetitive type.