Effects of long-term treatment with low-dose pravastatin on biliary lipid and bile acid composition in patients with nonfamilial hyperlipoproteinemia.

We tested the possibility that pravastatin, a competitive inhibitor of hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase, would alter cholesterol saturation of gallbladder bile by decreasing its cholesterol saturation index and/or degree of fatty acyl chain unsaturation in lecithin. Eighteen patients with type IIa hyperlipoproteinemia were treated with pravastatin 10 mg/d for 12 months. Gallbladder bile samples were aspirated with a duodenal tube by stimulating gallbladder contraction with intramuscular administration of cerulein before and after treatment. Serum cholesterol level was significantly reduced by 20% after 3 months, and this level was maintained after 12 months. In contrast, the cholesterol saturation index of gallbladder bile was not altered after 3 months (1.52 +/- 0.20 v 1.70 +/- 0.24), but it decreased significantly after 12 months (0.95 +/- 0.11, P < .01). The degree of fatty acyl chain unsaturation tended to decrease, although this was not statistically significant except for the decrease in molar percent of linoleate after 3 months. These findings suggest that long-term treatment with an inhibitor of HMG CoA reductase improves bile lithogenicity even at a comparatively low dose, and can decrease the incidence and complications of cholesterol gallstones.

Effects of fluvastatin on human biliary lipids.

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have rapidly become widespread in the treatment of hypercholesterolemia and are known to be variable in efficacy. To investigate the effect on biliary lipids, a 3-month study using fluvastatin was devised. A total of 19 patients were enrolled in this study: all had hypercholesterolemia (7 men, 12 women; 13 with type IIa, 6 with type IIb). After an observation period of 4-6 weeks with placebo, fluvastatin at a daily dose of 30 mg was administered for 3 months. Fasting blood samples were taken early in the morning, before, and once a month during 3 months of fluvastatin treatment, for measurement of serum lipids. Cerulein-stimulated bile in the gallbladder was sampled using a duodenal tube, and the changes in biliary lipids were assessed. There was a marked decrease in serum total cholesterol after 12 weeks of treatment (21%; p < 0.001). However, there was no significant difference in the bile cholesterol saturation index (CSI): values before and after 3 months of drug administration were 0.93 and 0.99, respectively (Admirand-Small method). There were no significant changes in either the fatty acid composition of biliary lecithin or in the bile acid composition of bile. In conclusion, on the basis of these results, short-term (3 months) administration of fluvastatin does not appear to affect CSI.

Primary malignant melanoma of the esophagus--a case report.

An unusual case of primary esophageal melanoma is reported herein. A 68 year old man who had experienced occasional dysphagia for about one month without suffering any weight loss was admitted to our department. An esophagogram revealed two lobulated masses and esophagoscopy showed a pigmented tumor in one of the masses. Curative surgery was thus performed through a right thoracotomy. The macroscopic appearance of the resected specimen was very unusual and it was subsequently proven to be primary malignant melanoma of the esophagus by histological examination. Postoperatively, cyclophosphamide and interleukin-2 were administered intravenously, followed by lymphokine-activated killer therapy. However, multiple liver metastases were found on a CT scan, 3 months after the operation and he died about 1 month later. The operative indications for primary malignant melanoma of the esophagus are discussed in this report.

The increase in putrescine content in the gastric mucosa of rats with ulcerations induced by restraint-immersion stress.

By means of high-performance liquid-chromatography, the putrescine, spermidine and histamine contents in the gastric mucosa were examined during the course of ulceration in rats by the restraint-immersion stress. (1) The putrescine content increased progressively during the course of ulceration with the continuing stress whereas after being released from the stress the content decreased gradually to a significantly lower level than that immediately after 12 hours of the stress. (2) The spermidine content in the gastric mucosa was unchanged during the course of ulceration with continuing stress nor after being released from the stress. (3) The mucosal histamine content decreased significantly after 4 hours under the continuing stress. (3) Extensive histological examination revealed the appearance of regenerating epithelium 36 hours after being released from the stress whereas no such finding was seen before that period. From the above findings, it has been speculated that the increase in the gastric mucosal putrescine content during the course of ulceration induced by restraint-immersion stress is probably due to the stimulated adrenal function by the stress, independently of the regeneration of gastric mucosa.

Increase in pepsin content in gastric mucosa during the course of aspirin- and taurocholate-induced gastric ulceration in rats.

To investigate the possible role of pepsin in ulceration induced by hydrogen ion back-diffusion, the ratio of alkali-labile pepsinogen to total pepsinogen was studied during the course of aspirin- and taurocholate-induced gastric ulceration in comparison with the changes in the ion permeability and histological findings. The results obtained were as follows. (1) The increase in the ulcer index was observed between 1 and 2 hr with intragastric aspirin and between 2 and 4 hr with intragastric taurocholate. (2) The back-diffusion of luminal hydrogen ions, observed as a significant decrease in hydrogen ion net flux, occurred immediately in both cases with aspirin and with taurocholate. (3) A significant increase in the ratio of alkali-labile to total pepsinogen in the homogenate of gastric mucosa was observed at 30 min with aspirin and at 60 min with taurocholate. (4) Histological examination revealed the degeneration of mucosal cells spreading from the luminal surface into the mucosa, which fell off after 120 min with aspirin. These findings indicate that the activated pepsin is involved in the ulcer formation caused by the hydrogen ion back-diffusion, although the origin of the activated pepsin is not clear at the present time.