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Biomedical subjects

R Coleman

Publications and source records attributed to R Coleman.

At least 217 records · Page 12Linked to original sources
PubMed1992

Ondansetron compared with metoclopramide in the control of emesis and quality of life during repeated chemotherapy for breast cancer.

This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide greater than or equal to 500 mg/m2). Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p less than 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p less than 0.001). The results for nausea also revealed highly statistically significant treatment differences (p less than 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p less than 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with 'none' or 'mild' nausea compared with 27% of patients receiving metoclopramide (p less than 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p less than 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19% of patients in the metoclopramide group and resulted in 15% of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Cholyl-lysylfluorescein: synthesis, biliary excretion in vivo and during single-pass perfusion of isolated perfused rat liver.

A fluorescent bile salt, cholyl-lysylfluorescein (cholyl-lys-F), was synthesised so that it retained both an intact steroid ring and a side chain structure with an unblocked carboxyl group. Its biliary kinetics and hepatic extraction were studied in Wistar rats and in the isolated perfused rat liver, respectively. The synthetic method used excess N-epsilon-CBZ-l-lysine methyl ester hydrochloride (7 mmol) and cholic acid (5 mmol) via EEDQ with a yield of 94% for cholyl-lys. Cholyl-lys-F was synthesized employing equimolar amounts of cholyl-lys (sodium salt) and fluorescein isothiocyanate (FITC) in bicarbonate buffer (pH 9.5) over 16 h at room temperature (21 degrees C) with a yield of 70%. The fluorescent property of cholyl-lys-F was similar to fluorescein with a strong apple-green fluorescence. In bile-fistula rats under pentobarbital anaesthesia, the cumulative 20 min biliary excretion as a percentage of injected dose were as follows: cholyl-lys-F, 94.4 +/- 0.3%, [14C]cholylglycine (CG), 93.1 +/- 1.2% and fluorescein (F), 34.8 +/- 0.5. Furthermore the single-pass hepatic extraction of cholyl-lys-F was 64.1 +/- 3.9%, [14C]CG was 66.1 +/- 1.2% and F was 16.5 +/- 2%. The similarity in biliary output and hepatic extraction of cholyl-lys-F to that of the natural bile acid cholylglycine suggest that both compounds are handled in a similar fashion. The greater biliary excretion and hepatic extraction of cholyl-lys-F relative to free fluorescein further suggest that conjugation with a bile salt may be an efficient way of targeting compounds to the liver.

Animals↗
PubMed1991

The induction of lamellar stacking by cholesterol in lecithin-bile salt model systems and human bile studied by synchrotron X-radiation.

Small angle X-ray scattering (SAXS) with synchroton radiation was used to investigate interactions among lipid particles in lecithin-bile salt model systems and in native gallbladder biles. In model systems in the absence of cholesterol, isotropic, continuous spectra were found, indicating the absence of periodic structures. In the presence of excess cholesterol, interaction in the form of lamellar stacking was detected by the appearance of discrete diffraction peaks. In the supersaturated cholesterol region of the commonly accepted phase diagram [1], where cholesterol crystals were expected, we found lamellar stacking. The high proportion of cholesterol to bile salts seems to be the common denominator of these models. The lamellar stacking was also found in native unprocessed bile. This effect of cholesterol on lipid structure has not been previously described. Lamellar stacking may contribute to cholesterol solubilization. Its influence on the kinetics of cholesterol crystallization is presently unknown.

Bile↗
PubMed1991

Disk drusen and angioid streaks in pseudoxanthoma elasticum.

Visual field loss secondary to optic disk drusen became evident before the development of angioid streaks in a patient with pseudoxanthoma elasticum. The incidence of optic disk drusen in cases of pseudoxanthoma elasticum is 20 to 50 times greater than that in the healthy population. We postulate that the abnormal aggregation of macromolecules with a high affinity for calcium (resulting in abnormalities in elastin in cases of pseudoxanthoma elasticum) also develops at the cribriform plate, disrupting axonal flow and leading to disk drusen formation. Pseudoxanthoma elasticum is associated with marked cardiovascular and gastrointestinal morbidity. Moreover, macular hemorrhage and precipitation of angioid streaks have frequently been noted after trauma. Prompt diagnosis of pseudoxanthoma elasticum will allow necessary prophylaxis and must be considered in patients with optic disk drusen.

Adult↗
PubMed1991

A 51Cr release cytotoxicity assay for use with human intrahepatic biliary epithelial cells.

Human intrahepatic biliary epithelial cells are important immune targets in a variety of hepatobiliary diseases particularly primary biliary cirrhosis and primary sclerosing cholangitis. The ability to isolate and maintain these cells in short term primary tissue culture has permitted us to develop an in vitro cytotoxicity assay for the study of these cells as potential targets to a variety of toxic stimuli. We have therefore established a chromium-51 (51Cr) release cytotoxicity assay for use with primary cultures of human intrahepatic biliary epithelial cells. The method is simple, reproducible and is more sensitive than dye exclusion, light microscopy and release of lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase.

Alanine Transaminase↗
PubMed1991

Purification of hepatocyte couplets by centrifugal elutriation.

An initial preparation of rat hepatocytes containing approximately 30% couplets was enriched by centrifugal elutriation. Of the couplets loaded onto the elutriator, 87% were eluted at medium flow rates of 60 to 80 ml/min at a rotor speed of 1,100 rpm; cells eluted in this range maintained a viability of more than 95%. Peak fractions were enriched in couplets to 84.5% +/- 2.5%. After elutriation, couplets retained the ability to secrete fluorescent cholephiles into sealed canalicular vacuoles. The preparation can now be used in hepatobiliary and hepatotoxicity studies not possible with preparations in which they are minor components.

Animals↗
PubMed1991

Advanced multiple beam equalization radiography (AMBER) in the detection of diffuse lung disease.

To evaluate the effects of scanning equalization radiography (SER) on the detection of diffuse lung disease a clinical comparison between an Advanced Multiple Beam Equalization Radiography (AMBER) unit and conventional chest radiography was performed. Even though the overall detection of focal pulmonary lesions with the AMBER unit has been shown to be significantly higher than with conventional radiography because of the improved demonstration of the costophrenic and retrocardiac regions, the utility of AMBER in the demonstration of diffuse lung disease has not been established. Twenty-one patients with diffuse lung disease (fibrosing alveolitis or sarcoidosis) and six patients with no pulmonary disease had high kVp frontal and lateral chest radiographs on both an AMBER unit and a conventional chest stand. The pooled results of five observers using Receiver Operating Characteristic (ROC) analysis indicate that there is a slight improvement but no statistically significant difference in observer performance between AMBER (Area under the ROC curve AZ = 0.934) and conventional radiography (AZ = 0.868) in the task of detecting diffuse lung disease.

Evaluation Studies as Topic↗
PubMed1991

Efficacy and cost-effectiveness of antibiotic monitoring at a Veterans Administration hospital.

A rigorous, continuously monitored antibiotic programme was initiated at our Veterans Administration hospital following evidence of inappropriate antibiotic usage. Seven hundred and thirty-one patients, mainly male, with an average age of 60 years were involved in the study; 378 were evaluable prior to policy implementation and 273 subsequently. The overall prevalence of deaths and average length of antibiotic therapy were less during the post-policy period. The number of antibiotic doses per patient was decreased by 24%. Drug costs were reduced by 32% post-policy, due largely to increased use of the longer-acting cephalosporins ceftriaxone and cefotetan. A 23% reduction in antibiotic acquisition costs was achieved over the 3-year period of the study, without detrimental effects on patient outcome.

Anti-Bacterial Agents↗
PubMed1991

Immunocytochemical localization of chloramphenicol acetyltransferase as a single-cell marker of transfected and transgenic cells.

A technique is described for immunocytochemical localization of the bacterial gene product chloramphenicol acetyltransferase, which is a commonly used reporter gene in transfected and transgenic cells. The described procedure is capable of localizing the enzyme in individual cells, providing a means of determining the cell type(s) expressing a foreign construct in complex cultures or in tissue sections of transgenic mice.

Animals↗
PubMed1990

Menadione increases hepatic tight-junctional permeability. Its effect can be decreased by butylated hydroxytoluene and verapamil.

Infusion of menadione at two different doses [2.7 mg and 5.5 mg in 100 microliters of dimethyl sulphoxide (DMSO)] into perfused rat livers for 30 min caused no or a 6-fold increase respectively in junctional permeability to horseradish peroxidase as compared with controls receiving 100 microliters of DMSO alone. The total glutathione (GSH) contents in these livers measured at the end of the experiments were 115% and 53%, compared with the controls. The free-radical scavenger butylated hydroxytoluene (BHT) (final concn. 5 microM) protected against the GSH depletion caused by the higher dose of menadione and partially decreased the menadione-induced increase in junctional permeability. Verapamil, a Ca2(+)-channel blocker which was added into the perfusion medium (final concn. 40 microM) 10 min before the infusion of 5.5 mg of menadione, completely abolished the effect of menadione on junctional permeability. Menadione exposure therefore increases tight-junctional permeability in the liver; this may involve a depletion of GSH and a subsequent increase in intracellular Ca2+.

Animals↗