Roger L. Gebhard

Clinical and endoscopic findings in patients early in the course of clostridium difficile-associated pseudomembranous colitis

Endoscopic and clinical features are reported for 39 patients detected early in the course of pseudomembranous colitis. Disease was detected early by virtue of careful surveillance in patients in whom diarrhea developed. Early proctosigmoidoscopic findings in pseudomembranous colitis are illustrated. Clinical presentation includes development of fever, leukocytosis, abdominal pain, and even an ileus picture on radiography in addition to diarrhea.

Sclerotherapy for actively bleeding esophageal varices in male alcoholics with cirrhosis

BACKGROUND Male alcoholics hospitalized with actively bleeding esophageal varices were treated with sclerotherapy or sham sclerotherapy and the outcomes during the index hospitalization were compared. METHODS The 87 patients were a subset of 253 patients enrolled in a prospective, randomized, single-blind, multicenter, controlled trial conducted in 12 VA medical centers. The patients (44 sclerotherapy, 43 sham therapy) were actively bleeding from esophageal varices at either randomization endoscopy (49) or follow-up endoscopy (38). Events and resource use during the index hospitalization were recorded. RESULTS In 40 (91%) of the sclerotherapy and 26 (60%) of the sham therapy patients, bleeding was stopped during the endoscopy session (p < 0.001). During the hospitalization, 10 (25%) sclerotherapy and 21 (49%) sham therapy patients died (p = 0.04, relative risk 2.17, 95% CI [1.02, 4.61]); 9 sclerotherapy and 22 sham therapy patients rebled (p = 0.005). The median transfusion requirement was higher for sham therapy (8 vs 4 units, p = 0.001), the number of median ICU hours was greater (101 vs 55, p < 0.001), and more patients in this group required shunt surgery (6 vs 0, p = 0.01). CONCLUSION Sclerotherapy, compared to no sclerotherapy, stops hemorrhage from actively bleeding esophageal varices and reduces use of resources. Sclerotherapy significantly increased hospital survival.

Efficacy of routine fiberoptic endoscope cleaning and disinfection for killing Clostridium difficile.

We have evaluated a standard procedure for cleaning and disinfection of endoscopes for efficacy in eradicating a spore-forming bacterial organism, Clostridium difficile. Initially, 23 endoscopes were cultured for the presence of C. difficile after hanging in storage for at least 24 hours after cleaning and disinfection. All cultures were negative. Subsequently, endoscopes used in 15 patients who had stool cultures positive for C. difficile were cultured immediately after use and again after cleaning and disinfection with 2% alkaline glutaraldehyde for 5 min. Ten of 15 (67%) endoscopes were culture positive for C. difficile immediately after use. After cleaning and disinfection, all of the endoscopes were culture negative except one, which yielded two negative cultures and two cultures showing late growth of rare C. difficile colonies, but contamination could not be ruled out. In vitro exposure to 2% alkaline glutaraldehyde for 5 min resulted in 99% or greater killing of C. difficile spores. We conclude that cleaning and a minimum of 5 min of disinfection with 2% alkaline glutaraldehyde are likely to be effective in killing C. difficile vegetative organisms and spores on endoscopes.

The effects of several weeks of ethanol consumption on ethanol kinetics in normal men and women

We examined in normal men and women the effects of chronic ethanol consumption and the coadministration of cimetidine and ranitidine on the kinetics of ethanol. We found that the consumption of 45 gm ethanol per day for 3 weeks increased the apparent volume of distribution of ethanol in men from 732 to 884 ml/kg (P < 0.01) but had no such effect in women (697 ml/kg before ethanol and 746 ml/kg after chronic ethanol consumption). This combined therapy had no effect on the rate of ethanol disappearance in either sex. In men the rate of disappearance was 165 mg/L/hr before and 168 mg/L/hr after chronic consumption, while in women the respective values were 209 and 203 mg/L/hr. The addition of either cimetidine or ranitidine had no effect on either parameter compared with values observed on day 22 of the study. In view of the known inhibitory effects of cimetidine on cytochrome P‐450–dependent enzymes, our data suggest that this enzyme system does not metabolize a significant fraction of ingested ethanol in subjects who have consumed moderate doses of alcohol for several weeks.

Cryptosporidial Carriage without Symptoms in the Acquired Immunodeficiency Syndrome (AIDS)

Excerpt To the Editor:Although cryptosporidial infections may cause severe, prolonged, and occasionally fatal diarrheal disease in persons with the acquired immunodeficiency syndrome (AIDS) (1, 2),...

Effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition on human gut mucosa

Mevalonic acid is an important biochemical intermediate in cholesterol synthesis and other processes involved in cell replication. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is the enzyme which catalyzes mevalonic acid synthesis. To determine whether a potent competitive inhibitor of this enzyme, the drug simvastatin, may have an adverse effect on enterocyte cell replication and cholesterol metabolism, small intestinal biopsies from nine hypercholesterolemic subjects were obtained before and during treatment with simvastatin as a lipid-lowering agent. Histologic review of biopsies in a blinded manner detected no change in ratio of villous length to crypt length or in mitotic index which might indicate altered cell replication. Similarly, no significant change in measured activity of HMG-CoA reductase activity was observed. In spite of the high exposure of jejunal mucosal cells to this potent competitive inhibitor of a key enzyme, no adverse effect on growth could be detected.

Gallstones in chronic spinal cord injury: Is impaired gallbladder emptying a risk factor?

OBJECTIVE To confirm that spinal cord injured persons are susceptible to gallstones and to evaluate the role of gallbladder stasis as a risk factor. STUDY DESIGN Twenty-nine subjects with chronic spinal cord injury underwent fasting ultrasonography to determine the incidence of gallstones and to quantitate gallbladder emptying response to a 20g fat liquid meal. Gallbladder emptying fraction was compared to that of healthy subjects studied concurrently. RESULTS Gallstones or sludge were found in 6 spinal cord injured men, a minimal prevalence of 21%. Four additional subjects had prior cholecystectomy for stones, giving a potential maximal prevalence of 30%. Four of the 6 subjects had gallstone risk factors of diabetes, obesity, and/or family history. Gallbladder stasis was not apparent in chronic spinal cord injured subjects. Only 5 subjects had poor gallbladder emptying, and 4 of them had diabetes and/or obesity. CONCLUSIONS The study confirms an increased prevalence of gallstones after spinal cord injury. However, gallbladder stasis did not appear to be etiologic, and most gallstones were associated with conventional risk factors. The results do not support a general policy of gallstone screening or prophylactic therapy after spinal cord injury.

Transport of circulating serum cholesterol by human renal cell carcinoma.

Clear cell renal cancer contains a large quantity of cholesterol ester (300-mg./gm. protein). To determine whether abnormalities in cholesterol transport could account for this sterol accumulation, the uptake, release, and imaging capabilities of intravenously injected 131I-6-iodomethyl-29-norcholesterol, a cholesterol analogue, were studied preoperatively in five patients with clear cell renal cancer. At surgery, samples of the liver, tumor, adrenal, and non-tumor kidney were obtained for analysis. 131I-sterol uptake by the tumor, when normalized for cholesterol content, was less than for adrenal, liver or kidney. In contrast, release of preloaded 131I-sterol from the human tumors was consistently slower than for normal kidney. The reduced release of free cholesterol from renal cancer cells may, in part, be responsible for the accumulation of cholesterol in human renal cancer.

Thyroid hormone is required for dietary fish oil to induce hypersecretion of biliary cholesterol in the rat

In the rat, both fish oil diet and thyroid hormone replacement are reported to augment bile cholesterol secretion out of proportion to bile flow or secretion of other bile lipids. We sought common mechanisms for these effects and evaluated the role of phospholipid fatty acid composition in the process. Methimazole-treated hypothyroid rats were fed low-fat chow or chow supplemented with 10% corn oil or fish oil, and were studied before and after thyroid hormone treatment. Serum, hepatic, and bile lipids were measured, phospholipid fatty acid composition determined, and hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity assayed. Fish oil diet stimulated cholesterol secretion into bile only after thyroid hormone was given, and this action was synergistic with that of thyroid hormone. Reduced serum cholesterol in fish oil-treated rats was associated with increased biliary cholesterol secretion and diminished hepatic cholesterol content. This suggests that augmented biliary cholesterol secretion may contribute to the fish oil-induced reduction of serum cholesterol. No definite relationship between hepatic or biliary phospholipid fatty acid composition and biliary secretion was apparent, although high bile cholesterol secretion was associated with a low percentage of hepatic and bile phospholipid linoleic acid.

Diurnal rhythm of HMG CoA reductase activity in canine intestine is independent of luminal contents.

Activity of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34) measured in isolated segments of canine intestinal mucosa showed a distinct diurnal rhythm. Total activity changed over a twofold range with a peak occurring during midday, shortly after feeding. Since the isolated segments had no contact with luminal contents, the rhythm was not directly related to food components or bile salts. Humoral or neural influences must mediate the rhythm. The diurnal rhythm persisted for at least 3–5 mo, but was lost by 10 mo following formation of the isolated segment, possibly because of mucosal involution.