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Biomedical subjects

K R Larsen

Publications and source records attributed to K R Larsen.

41 records · Page 3Linked to original sources

The cytoprotective effects of (+/-)-15-deoxy-16-alpha, beta-hydroxy-16-methyl PGE1 methyl ester (sc-29333) versus aspirin-shock gastric ulcerogenesis in the dog.

SC-29333 (SC) has been reported to protect the gastric mucosa from the effects of topical aspirin. We compared SC and 16,16-dimethyl PGE2 (16-dm) in 20 chambered canine stomachs (6 controls and 7 of each PG). Prostaglandin was added to an acid solution (100 mM HCl; 54 mM NaCl) at 0, .001, .01, 0.1, and 1.0 microgram/ml (two periods each). Then aspirin (20 mM) and PG (1.0 microgram/ml) (two periods) were followed by hemorrhagic shock (near 60 mm Hg mean arterial pressure). 16-dm caused a significant efflux of fluid (-6.5 +/- 5.3 to 17.3 +/- 6.7 microliters/min), Na+ (2.1 +/- 0.5 to 6.8 +/- 1.6 muEq/min), and Cl- (-0.9 +/- 2.4 to 5.3 +/- 1.3 muEq/min), but did not affect K+ or H+. 16-dm also caused a slight drop in potential difference (PD) (67.6 +/- 1.7 to 60.3 +/- 2.0 mV). 16-dm did not significantly affect total blood flow. Percent lesion formation was more severe than controls (20.2 +/- 3.5 vs 11.6 +/- 1.7 percent) but not statistically significant. SC had no significant effect on fluid, H+, Na+, K+, or Cl-. It caused an increase in blood flow (6.85 +/- 1.46 to 26.20 +/- 2.74 ml/min, p less than .001). SC significantly reduced percent lesion formation (1.9 +/- 0.9% p less than .001). We conclude: 1) SC causes an increase in mucosal blood flow and protects from aspirin-shock ulcerogenesis. 2) 16-dm stimulates an efflux of non-parietal extracellular fluid and fails to protect against aspirin injury during mucosal ischemia. 3) SC cytoprotection may be mediated by increased mucosal blood flow. 4) The mechanism of cytoprotection with 16-dm may require sufficient mucosal blood flow for filtration of non-acid fluid from blood to gastric lumen.

Animals↗

Controlled intragastric pH and cimetidine inhibition of histamine-stimulated gastric acid secretion in the dog.

This study tested a circulating intragastric titration system with an examination of the kinetics of cimetidine inhibition of histamine-stimulated gastric acid secretion of pH 7.0. Dogs were anesthetized, intubated with a biluminal nasogastric device, and connected to the titrating system. The dogs were stimulated with histamine at 0.0, 0.25, 0.50, 1.0, 2.0, and 4.0 microgram/kg/min IV. The dose variations were repeated on separate days with cimetidine infusion at 0.0, 20, and 40 microgram/kg/min IV. Calculated maximal response was 4.52 mEq/kg/hr. Histamine D50 was 0.60 microgram/kg/min. Cimetidine ID50 was 22.6 microgram/kg/min when histamine was given at 1.0 microgram/kg/min. Although acid secretion was higher than other published values, cimetidine inhibition kinetics were not significantly different from published values. A positive correlation was found between cimetidine ID50 and the logarithm of the histamine infusion rate. Our data suggest that (1) a simple circulating intragastric titration system can give accurate results in acid secretion studies, (2) increased gastric pH may enhance histamine-stimulated acid secretion, (3) neutralization of gastric contents does not interfere with cimetidine inhibition kinetics which is competitive, and (4) at artifically high rates of histamine infusion, cimetidine can actually increase acid secretion. We suggest that a circulating intragastric system may be tested in a surgical intensive care unit to evaluate potential clinical value in antiulcer therapy.

Animals↗

A comparison of two different dosages of pivampicillin and doxycycline in patients with gynaecological infections.

The efficacy of 500 mg pivampicillin twice daily, 350 mg pivampicillin 3-times daily and 100 mg doxycycline daily was compared in 106 patients with salpingitis, parametritis or endometritis. Both the pivampicillin regimens were equally effective. The average duration of therapy needed to produce a satisfactory clinical response was shorter with pivampicillin (14 days) than with doxycycline (21 days). Pivampicillin improved the patients' gynaecological status in 90% of the subjects treated compared to only 70% of patients given doxycycline. Fewer relapses were recorded in women given pivampicillin (4%) than in subjects treated with doxycycline (15%). Gonococci were isolated from 10% of vaginal swabs. The involvement of Chlamydia and Mycoplasma was not studied. However, the high cure rate indicated that, if present, they did not pose a therapeutic problem. Side-effects, mainly dyspepsia, were observed in 2 patients in each group. The twice-daily administration of pivampicillin is recommended, since it is more practical and increases patient compliance.

Adult↗