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R L Fisher

Publications and source records attributed to R L Fisher.

At least 37 records · Page 2Linked to original sources
PubMed1995

Stress-related mucosal disease. Pathophysiology, prevention, and treatment.

The advent of gastrointestinal endoscopy has allowed us to follow the morphologic results of severe stress on the gastrointestinal mucosa. It has become clear, however, that the presence of mucosal abnormalities does not always correlate with the presence of overt bleeding, or with the effect of bleeding on the overall outcome of such patients. In fact, the incidence of severe gastrointestinal hemorrhage, secondary to stress-related mucosal disease, has been decreasing over the past decade, as the care of these critically ill patients has improved. In patients who do have overt hemorrhage, however, the mortality rate is extremely high. It therefore remains the duty of the clinician to identify patients who are at high risk of having overt hemorrhage, and ensure that they receive adequate prophylactic therapy.

Anti-Ulcer Agents↗
PubMed1994

Nutrition support in inflammatory bowel disease.

The mechanisms of nutritional therapy in inflammatory bowel disease have not been thoroughly established. It is likely that a further understanding of the underlying disease process will allow better understanding of these forms of therapy, with a sounder rationale for the construction of specific diet constituents for therapy. Regardless, nutritional therapy is likely to be multidimensional, and various forms may affect different aspects of the disease process. Decreased inflammatory factors, decreased antigenic stimuli, provision of essential nutrients, improved immune function, and other factors may all be of varying importance in different patients with inflammatory bowel disease. Little work has been done on the role of diet therapy in the long-term treatment of patients with inflammatory bowel disease as a method of preventing relapse. Parenteral nutrition and elemental diets appear to have limited roles in this area. Some investigation has been done to see if minor modifications of the normal diet can prolong remission periods. Low-fiber diets are frequently recommended for patients with strictures. Whether this has any significant effect on symptoms, inflammation, or complications is unclear. Heaton et al suggested that a high-fiber, unrefined carbohydrate diet resulted in fewer and shorter hospitalizations. In a prospective follow-up study by Ritchie et al, however, these results were not able to be reproduced. Exclusion diets have also been suggested as a means of reducing relapse rates in patients with Crohn's disease. In a small, randomized, controlled trial of an exclusion diet versus an unrefined carbohydrate, fiber-rich diet, there were significantly fewer relapses among the patients treated with the exclusion diet at 6 months. These diets require intensive patient cooperation, but the potential side effects are minimal. Clearly, these findings need to be reproduced in large, prospective, randomized, controlled studies before widespread use can be advocated. A great deal of data exists on the use of nutritional supplementation in the treatment of inflammatory bowel disease, although little of it is in the form of large, randomized, controlled studies. Nutritional manipulation currently has a limited role in patients with ulcerative colitis; a much broader role exists in patients with Crohn's disease. The mechanisms by which nutritional therapy affects these diseases may include a combination of factors--decreased antigenic exposure, improved immune function, and provision of essential nutrients and calories needed for bowel regeneration.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1994

The use of human lung slices in toxicology.

1. Successful use of agar-filled precision-cut rat lung slices in dynamic organ culture prompted the use of this technology with human lung. 2. The larger tissue mass of a human lung required that the trachea be cannulated with a balloon catheter and subsequently inflated with 4 liters of warm agar/medium mixture and then cooled before being precision-cut into 500 microns thick slices. 3. To characterize the human lung slices, viability and the effects of acrolein and nitrofurantoin were assessed over a period of 24 h using protein synthesis and nonprotein sulfhydryl content. 4. Control human lung slices synthesized protein at a linear rate and maintained a stable nonprotein sulfhydryl content for 24 h. 5. Slices incubated with acrolein exhibited no significant decrease in protein synthesis or nonprotein sulfhydryl levels until 24 h. 6. Incubation with nitrofurantoin exhibited a definite time- and dose-dependent inhibition of protein synthesis, and depletion of the cellular thiol pool. 7. These results indicate that this human lung tissue slice system may be used as an in vitro model to identify and screen pneumotoxicants.

Acrolein↗
PubMed1994

Toxicity of cisplatin and mercuric chloride in human kidney cortical slices.

1. Organ specific toxicity such as nephrotoxicity is often investigated with the use of in vivo or in vitro animal models. 2. It would be beneficial if these findings could be verified in a human in vitro system which utilizes non-transplantable human kidneys. 3. Non-transplantable human kidneys were decapsulated, cut in half along the long axis, cores made perpendicular to the hemisphere, and precision-cut renal cortical slices produced. 4. These human kidney slices were incubated for 3, 6, 12, 18 and 24 h, viability assessed using intracellular K+ content, protein synthesis and organic ion transport and the potential nephrotoxicity of cisplatin (0.25, 0.5 and 1.0 mM) and mercuric chloride (10, 50 and 100 microM) on these slices were examined. 5. Control human kidney slices were viable for up to 24 h using all viability parameters while a dose- and time-dependent toxic response was seen using both cisplatin and mercuric chloride. 6. Cisplatin was more nephrotoxic in this human in vitro system than in previously investigated in vitro animal systems whereas mercuric chloride was similar in both systems. 7. These results indicate that human renal cortical slices are useful in predicting and verifying potentially nephrotoxic compounds in man.

Adolescent↗
PubMed1994

Transient regional osteoporosis of the ankle and foot. A report of four cases and review of the literature.

Transient regional osteoporosis of the ankle and foot is an uncommon clinical entity characterized by local tenderness over the involved area. Plain radiographs demonstrate osteopenia of the involved bone and technetium diphosphonate bone imaging shows increased tracer uptake at the same location. This disorder is benign and self-limiting, and treatment is conservative.

Ankle Joint↗
PubMed1993

Cold- and cryopreservation of human liver and kidney slices.

Tissue slices may provide a rapid and economical way of determining cold ischemic effects on human liver and kidney cell viability and metabolism. In contrast to isolated hepatocyte cultures, tissue slices offer an in vitro system which more closely resembles the in vivo situation because of the differentiation and functional heterogeneity of the slice. In this study, human liver and kidney slices were cold stored for 10 days in Belzers University of Wisconsin (UW), Euro-Collins, and Modified Sacks solutions. Another set of slices was cryopreserved at 1 degree C/min for liver and 12 degrees C/min for kidney using a 10% dimethyl sulfoxide/fetal calf serum (FCS) cryoprotectant solution. The cold- and cryopreserved slices were incubated in roller culture for 4 h using FCS as the media. Liver slice viability was assessed by K+ content, protein synthesis, gluconeogenesis, and urea synthesis. Kidney slice viability was assessed using K+ content, protein synthesis, and organic ion transport (PAH and TEA). Human kidney slices were cold preserved in UW for 4-6 days, while the human liver slices were preserved for 12-24 h depending on the viability parameter. Following cryopreservation, human liver slice viability was retained at between 65 and 90% of control values, while kidney slice viability was maintained between 70 and 90% of control values depending on the viability parameter. These results indicate that this human in vitro tissue slice system can be used to optimize preservation solutions and methods. The ability to cold- and cryopreserve human slices could facilitate the more efficient utilization of human tissue.

Analysis of Variance↗
PubMed1993

Culture medium composition affects the relative toxicities of chlorobenzenes in rat liver slices and the isolated perfused liver.

The effects of different media composition on the hepatotoxicity produced by monochlorobenzene (MCB), 1,2-dichlorobenzene (1,2-DCB), 1,3-dichlorobenzene (1,3-DCB) and 1,4-dichlorobenzene (1,4-DCB) were examined in two different in vitro systems. The toxicity of these chlorobenzenes was investigated in the perfused rat liver and liver slices using Krebs-Henseleit buffer. Significant differences between the chlorobenzenes were apparent in the perfused liver but not in the tissue slices. However, a dose and time related response of rat liver slices to the chlorobenzenes was observed. Partial amelioration of the chlorobenzene toxicity was observed when the Krebs-Henseleit buffer was supplemented with vitamins, amino acids, and/or bovine serum albumin. 1,2-DCB and 1,3-DCB toxicity was affected by amino acids and vitamins. The toxicity produced by 1,4-DCB was suppressed by amino acids, vitamins and 1% BSA. MCB hepatoxicity could only be suppressed by 1% BSA. This data suggests that tissue culture media composition plays a major role in the hepatotoxicity of the chlorobenzenes.

Animals↗
PubMed1993

New therapies for idiopathic ulcerative colitis.

Medical and surgical management of ulcerative colitis has advanced far in the last decade. New time-released ASA compounds and enemas have decreased the side effects of sulfasalazine and allowed delivery of higher doses of the active compound to the site of action. New steroid compounds have reduced the potential for systemic adrenal glucocorticoid suppression. However, therapy is still directed only against secondary immune and inflammatory responses. Until the cause of UC is discovered, well-designed and well-performed clinical trials must continue to try to identify agents that combine low toxicity with high therapeutic potential.

Adrenal Cortex Hormones↗
PubMed1991

The lack of relationship between hepatotoxicity and lithocholic-acid sulfation in biliary bile acids during chenodiol therapy in the National Cooperative Gallstone Study.

To test whether hepatotoxicity occurring in National Cooperative Gallstone Study patients was caused by a toxic effect of chenodiol per se or of lithocholate caused by defective sulfation, bile samples were analyzed using a new high-performance liquid chromatography method that measures the proportions of the four individual lithocholate amidates (sulfated and unsulfated lithocholylglycine and lithocholyltaurine) and all common bile acid amidates. Samples were obtained from National Cooperative Gallstone Study patients (n = 17) with abnormal light microscopic liver biopsy results or major aminotransferase elevations and from a matched control group of patients (n = 14) who received similar chenodiol doses but had no evidence of liver injury. Bile samples from 45 healthy subjects were also analyzed. The analytical method was validated by showing that the percentage of chenodiol and cholic and deoxycholic acid obtained by high-performance liquid chromatography correlated highly (r greater than 0.94) with previous gas-liquid chromatography analyses of these samples by the National Cooperative Gallstone Study Reference Laboratory. No significant differences were seen between gallstone patients with and without evidence of liver injury for percent total lithocholate amidates, percent sulfated or unsulfated lithocholate amidates or percent chenodiol amidates. Lithocholate was partially sulfated in all bile samples (52% +/- 17% [mean +/- S.D., n = 50]), but the extent of sulfation varied widely between and within patients during the course of therapy. Mean values of healthy subjects were similar and also showed a wide range in the extent of lithocholate sulfation. It is concluded that (a) liver injury caused by these doses of chenodiol could not be attributed to the accumulation of unsulfated lithocholate per se in circulating bile acids; (b) liver injury appeared to be, directly or indirectly, caused by enrichment in circulating bile acids with chenodiol or chenodiol together with lithocholate, suggesting that the hepatocytes of those patients with hepatotoxicity were injured by the change induced in bile-acid metabolism by the feeding of chenodiol; and (c) about half of lithocholate amidates in bile samples were sulfated, but the extent of sulfation was highly variable both in gallstone patients and healthy subjects.

Bile Acids and Salts↗
PubMed1991

Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial. The Boston-New Haven-Barcelona Portal Hypertension Study Group.

To assess the effectiveness of propranolol in the prevention of initial variceal hemorrhage, a double-blind, randomized trial was carried out in three centers. Patients with cirrhosis (78% alcoholic), hepatic venous pressure gradients greater than 12 mm Hg and endoscopically proven esophageal varices were randomly assigned to propranolol (51 patients) or placebo (51 patients). Of the 102 patients, 58% were Child's class A, 34% were Child's class B and 8% were Child's class C. Daily dosage was determined by the administration of progressively increasing doses of propranolol with the hepatic vein catheter in place to achieve a 25% decrease in hepatic venous pressure gradient, a decrease in hepatic venous pressure gradient to less than 12 mm Hg or a decrease in resting heart rate to less than 55 beats/min. During a mean follow-up period of 16.3 mo, 11 patients in the placebo group (22%) bled from esophageal varices compared with 2 in the propranolol group (4%) during a mean period of 17.1 mo (p less than 0.01). Three additional patients (6%) in the placebo group bled from portal hypertensive gastropathy compared with none in the propranolol group. Propranolol appeared effective in preventing bleeding from large varices. Eleven deaths (22%) occurred in the placebo group compared with eight deaths (16%) in the propranolol group (NS). The mean dose of propranolol was 132 mg/day, and the median dose was 80 mg/day. Using a compliance index (pill count, clinic attendance, alcohol and propranolol levels and alcohol history), 81% of the propranolol patients and 77% of the placebo patients were considered compliant. Complications severe enough to require cessation of therapy occurred in eight patients (16%) in the propranolol group and four in the placebo group (8%) (NS). We conclude that propranolol effectively prevents the first variceal hemorrhage in patients with alcoholic cirrhosis and large esophageal varices but does not improve survival.

Blood Pressure↗
PubMed1989

Hepatobiliary abnormalities associated with total parenteral nutrition.

Evidence of hepatic dysfunction (clinically, chemically, and morphologically) and biliary-tract abnormalities is common in patients receiving TPN. The entity might present as hepatocellular injury (fatty liver, steatonecrosis), intrahepatic cholestasis, acalculous cholecystitis, or cholelithiasis. Infants manifest primarily intrahepatic cholestasis, whereas adults manifest fatty liver early and intrahepatic cholestasis later in the course of therapy. Both groups are at risk for the development of biliary-tract abnormalities. Although most of these changes in the adult are mild and reversible, a small number of patients have recently been reported to develop progressive liver disease. In infants, however, the changes may be more severe, and lead more frequently to progressive liver disease and death. Although this progression to chronic liver disease is worrisome, it is uncertain whether, in patients on long-term therapy, it is due to the TPN or to other conditions or therapies associated with their clinical condition. The pathogenesis of each of these lesions may be multifactorial, including carbohydrate overfeeding, essential-fatty-acid deficiency, amino-acid deficiencies or imbalances, carnitine deficiency, bile-salt toxicity, lipid emulsions, bile-flow reduction, and gallbladder stasis. Therapies in these patients are aimed at alterations in the preceding etiologies (decreased glucose loads, contraction of the gallbladder). Further work is necessary to delineate the exact mechanisms of this entity, especially with regard to the causal relationships of TPN and this entity and to the development of chronic liver disease.

Adult↗
PubMed1989

Endemic fluorosis with spinal cord compression. A case report and review.

We report a case of spinal cord compression in a Mexican immigrant due to vertebral osteosclerosis from chronic fluoride intoxication. Endemic fluorosis is acquired through drinking water. Groundwater sources with high fluoride content occur worldwide. The epidemiology, metabolism, and clinical features of fluorosis are reviewed. Greater physician awareness of this entity is important to identify correctly patients with this unusual and potentially devastating clinical disorder.

Aged↗
PubMed1987

Adverse drug reactions.

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Drug-Related Side Effects and Adverse Reactions↗
PubMed1986

Duodenal ulcer. Incidence, risk factors, and predictive value of plasma pepsinogen.

In 1958 the Yale freshman class gave blood samples as part of a study intended to determine the predictive value of plasma pepsinogen (PP) for the subsequent development of duodenal ulcer (DU). We report a long-term follow-up of this cohort. A self-administered questionnaire designed to ascertain information about the development of peptic ulcers, and the presence of risk factors was mailed to 861 subjects with "active" addresses. A second questionnaire was mailed to each respondent's physician(s) to verify the diagnosis of DU. Completed questionnaires were returned, after three mailings, by 604 (70%) of the subjects. They reported 18 documented DUs, 15 since 1958, for an incidence of 1.1/1000 person years. Only smoking (P less than 0.05) and undergraduate physical inactivity (P less than 0.01) were identified as risk factors for DU. Family history; blood type; blood antigen secretor status; ingestion of coffee, alcohol, milk, salicylates, soda, or tea; and COPD were not identified as risk factors for DU. Patients with DU had higher mean PP values than those who did not (391.6 +/- 99.6 vs 346.6 +/- 106.7, mean +/- SD) but this was not statistically significant (P greater than 0.05). The predictive value of an elevated PP (greater than 450) for the development of DU was 7.9%, but a low or normal PP predicted the absence of a DU in 97.5% of subjects over a 22-year span.(ABSTRACT TRUNCATED AT 250 WORDS)

Duodenal Ulcer↗
PubMed1986

Gastrointestinal bleeding in competitive runners.

Competitive runners have been shown to develop previously undescribed clinical conditions, including "runner's anemia." This has been shown to be an iron-deficiency anemia of several etiologies including gastrointestinal bleeding. Although 8-23% of runners have been shown to have guaiac-positive stools after a marathon, the incidence of significant and prolonged bleeding is unknown. We report four cases of competitive runners with iron-deficiency anemia, gastrointestinal bleeding coinciding with running, and no definitive gastrointestinal pathology despite extensive evaluation.

Adult↗