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Biomedical subjects

R L Gebhard

Publications and source records attributed to R L Gebhard.

At least 37 records · Page 2Linked to original sources
PubMed1987

Abnormal cholesterol metabolism in renal clear cell carcinoma.

The clear cell form of renal cell carcinoma is known to derive its histologic appearance from accumulations of glycogen and lipid. We have found that the most consistently stored lipid form is cholesteryl ester. Clear cell cancer tissue contained 8-fold more total cholesterol and 35-fold more esterified cholesterol than found in normal kidney. Cholesteryl ester appeared to be formed intracellularly since it was not membrane-bound and since oleate was the predominant form, as opposed to linoleate in lipoprotein cholesteryl esters. The cholesterol in clear cell tumors did not appear to be a result of excessive synthesis from acetate since HMG-CoA reductase (EC 1.1.1.34) activity was lower in cancer tissue than in normal kidney (2.9 +/- 0.8 vs. 7.2 +/- 1.2 pmol/mg of protein per min). In contrast, intracellular activity of fatty acyl-coenzyme A:cholesterol acyl transferase (ACAT, EC 2.3.1.26) was higher in tumor tissue than in normal kidney (2405 +/- 546 vs. 1326 +/- 301 pmol/mg of protein per 20 min) while cytosolic cholesteryl ester hydrolase activity appeared normal. Cholesteryl ester storage in clear cell renal cancer may be a result of a primary abnormality in ACAT activity or it may be a result of reduced release of free cholesterol (relative to cell content) with a secondary elevation in ACAT activity.

Adenocarcinoma↗
PubMed1986

Innervation of periosteum and bone by sympathetic vasoactive intestinal peptide-containing nerve fibers.

Neural control of bone metabolism and growth has been suggested, although the identity of participating neurons and neurotransmitters effecting this control has not been established. Immunohistochemical studies demonstrated a system of vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers that innervate periosteum and bone in several mammalian species. Thoracic sympathetic chain ganglionectomy resulted in an ipsilateral loss of VIP-immunoreactive fibers in the periosteum of ribs, whereas dorsal root ganglionectomy had no effect. Injection of fast blue into rib periosteum labeled a population of VIP-immunoreactive sympathetic postganglionic neurons. Thus, postganglionic sympathetic neurons may provide an important means by which VIP regulates bone mineralization.

Animals↗
PubMed1986

Abnormal intestinal permeability to sugars in diabetes mellitus.

A test of intestinal mucosal function which utilizes the differential permeability of L-rhamnose and lactulose has been reported to be helpful in the diagnosis of gluten-sensitive enteropathy. We have applied this test to 48 male subjects with diabetes mellitus to evaluate its usefulness as a screening test in diabetic patients and to further study sugar absorption in these individuals. Total urinary lactulose excretion in the 13 healthy control subjects was 54.5 +/- 8.5 mg/5 h, while excretion by diabetic patients was increased at 116.1 +/- 15.7 mg/5 h (p less than 0.01). Similarly, total L-rhamnose excretion by diabetic patients was significantly higher (139.7 +/- 14.3 mg/5 h vs 84.3 +/- 18.4 mg/5 h, p less than 0.05). The ratio of percent urinary excretion for lactulose/L-rhamnose (L/R ratio) for diabetic patients (0.197 +/- 0.024) was not different from the control subjects (0.151 +/- 0.2). Nine out of 48 diabetic patients studied had lactulose/L-rhamnose ratios higher than the mean plus two standard deviations of the control group, which might lead to the diagnosis of small bowel mucosal disease. Although we may have been detecting subclinical mucosal disease or gluten sensitive enteropathy in a subgroup, it appears that this test of intestinal mucosal function should be interpreted with caution in diabetic patients.

Adult↗
PubMed1986

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.

Animals↗
PubMed1986

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.

Aldehydes↗
PubMed1986

Clostridium difficile-associated diarrhea and colitis in adults. A prospective case-controlled epidemiologic study.

In a one-year period, 149 adult cases of Clostridium difficile-associated diarrhea and colitis were compared with 148 diarrhea-free controls. Eighty-seven percent were nosocomial and 75% were on surgical services. Endoscopy revealed pseudomembranes in 51% of the 109 cases in which stool cytotoxin was present, compared with 11% of the 40 cases that were culture-positive but cytotoxin-negative. Cases diagnosed only by stool culture showed essentially no differences from controls, 21% of whom had asymptomatic stool colonization. We estimate that only 20% of these cases had diarrhea due to C difficile. Compared with controls, cases diagnosed by the presence of cytotoxin or pseudomembranes were found to have been hospitalized longer at diarrhea onset, to have had more antecedent infections, and to have received clindamycin, multiple antimicrobials, and therapeutic antimicrobials more often than controls, but controls received prophylactic antimicrobials more frequently than cases. Cultures of the environment, patients, and personnel failed to detect a mechanism of acquisition.

Adult↗
PubMed1985

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.

Adult↗
PubMed1985

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 less than 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.

Adult↗
PubMed1985

3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in the human gastrointestinal tract.

Activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34) was measured in intestinal mucosa of the human gastrointestinal tract. Activity was highest in gastric mucosa (18.2 pmol per mg per min) and there was a constant low level in the small bowel and colon (approximately 10 pmol per mg per min). Phosphorylation/dephosphorylation modulation of intestinal reductase activity was demonstrated in normal mucosa. Expressed jejunal reductase activity was significantly higher in celiac sprue mucosa and mucosa from defunctionalized intestine of jejunoileal bypass patients. Enzyme activity also increased during 24-hr mucosal organ culture in the absence of exogenous cholesterol. Addition to the culture medium of pure cholesterol or 25-hydroxycholesterol dissolved in a small volume of ethanol suppressed the culture-induced increase to 86 +/- 3% and 69 +/- 5% of paired controls, respectively. This evidence suggests that a moderate degree of feedback regulation of intestinal cholesterol synthesis by luminal sterol occurs in man. Mucosal HMG-CoA reductase activity was also measured in patients with hyperlipoproteinemia. Patients with either predominant hypercholesterolemia or predominant hypertriglyceridemia lipid profiles had "normal" expressed reductase activity, but feedback regulation by free cholesterol could not be demonstrated in either group under these conditions.

Biopsy↗
PubMed1983

Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis.

101 patients with Clostridium-difficile-associated diarrhoea or colitis were prospectively randomised to 10-day oral courses of metronidazole, 250 mg four times a day, or vancomycin, 500 mg four times a day. 7 did not complete the protocol and were dropped from analysis. Pseudomembranous colitis (PMC) was diagnosed after endoscopy in 33 patients. Of the remaining patients without PMC, 38 had both C difficile culture and cytotoxin and 23 had only culture evidence of C difficile. 52 evaluable patients received vancomycin and 42 received metronidazole. There were two treatment failures with metronidazole and none with vancomycin (p = 0.20); and two relapses with metronidazole versus six with vancomycin (p = 0.17). Treatment in 1 patient in each group was discontinued because of drug intolerance. Response and relapse rates of the 33 patients with PMC were no different from those of the remaining patients. Pharmacy cost for the dosage used was $387.48 to $520.00 for vancomycin and $11.84 for metronidazole. Metronidazole and vancomycin have equivalent efficacy and relapse rates and are tolerated to a similar extent by patients with C-difficile-related diarrhoea and colitis, but metronidazole is considerably more economical.

Adult↗
PubMed1983

Hepatic and intestinal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in genetically diabetic mice.

Cholesterol synthesis rate, as determined by 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, is characterized in the major organs of genetically diabetic mice. Both C57BL/Ks db+/db+ and C57BL/6 ob+/ob+ mice are hyperinsulinemic and insulin-resistant. These animals demonstrate loss of the circadian rhythm of hepatic reductase activity and a tendency for increased intestinal activity. As a result, proportionally more endogenous cholesterol synthesis occurs in intestinal mucosa than liver in genetically diabetic animals. Thus, the alterations in activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase which are observed in animal models of diabetes are the result of diminished insulin effect rather than insulin level.

Animals↗
PubMed1983

The effect of severe zinc deficiency on activity of intestinal disaccharidases and 3-hydroxy-3-methylglutaryl coenzyme A reductase in the rat.

Specific activities of five enzymes were measured in intestinal mucosa of zinc-deficient rats and compared to activities in appropriate zinc-sufficient controls. Three disaccharidases were found to be significantly reduced in zinc deficiency. Alkaline phosphatase, a zinc metalloenzyme, also showed reduced activity. Activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol synthesis, was elevated. It is possible that impaired carbohydrate digestion (reflected in disaccharidase activity) and even defective lipid absorption (reflected in reductase activity) may contribute to the poor nutrition and diarrhea of zinc deficiency.

Alkaline Phosphatase↗
PubMed1983

Effect of exorphins on gastrointestinal function, hormonal release, and appetite.

Peptic digestion of gluten results in the production of substances having opiatelike activity in bio- and receptor assays. These substances have been termed exorphins. In this study, we determined the effect of gluten, hydrolyzed gluten, and hydrolyzed gluten plus the opiate blocker naloxone on a variety of hormonal parameters, gastrointestinal transit time, small bowel mucosal integrity, and satiety. Hydrolyzed gluten prolonged intestinal transit time, and this effect was reversed by concomitant administration of naloxone. Hydrolyzed gluten also produced a naloxone-reversible increase in plasma somatostatinlike activity, which may have been responsible for the delayed transit time. No effects of the "exorphins" could be demonstrated on serum gastrin, cortisol, carbohydrate metabolism, or small bowel mucosal integrity. Although a number of studies have suggested a role for endogenous opiates in appetite regulation, we could not demonstrate any effect of "exorphins" on the amount of calories ingested nor on the perception of satiety. This study defines a potential role for small opiatelike peptides in foodstuffs in the regulation of intestinal function.

Adult↗
PubMed1982

Acute viral enteritis and exacerbations of inflammatory bowel disease.

In order to determine whether or not acute viral gastroenteritis predisposes to exacerbations of inflammatory bowel disease, patients with Crohn's disease and ulcerative colitis were observed longitudinally. Assessment of disease activity was correlated with evidence for viral infection by serology and stool antigen testing. Disease exacerbations were rarely associated with rotavirus, Norwalk agent, or adenovirus infection, primarily because these infection rates were very low. However, the few patients having these viral infections often had relapse symptoms.

Acute Disease↗