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Biomedical subjects

R Coleman

Publications and source records attributed to R Coleman.

At least 199 records · Page 11Linked to original sources
PubMed1993

Effects of niacin on biliary lipid output in the rat.

The mechanisms for the hypocholesterolaemic action of niacin (nicotinic acid) were examined in rats administered niacin at a dose of 400 mg/kg body wt/day for either 2 or 4 weeks. Another group of rats were administered diosgenin, an inhibitor of acyl-CoA:cholesterol acyltransferase, as a 1% (w/w) supplement in the diet for 7 days. Both agents produced small increases in bile flow rates (up to 40%) and mild hepatotoxicity evidenced by small increases in serum transaminase activities. Niacin treatment for 2 or 4 weeks lowered serum cholesterol concentrations by 13% or 29%, respectively, with the greatest decrease occurring in the low density lipoprotein fraction. This was accompanied by relatively large increases in biliary cholesterol output (114% and 130% after 2 and 4 weeks treatment, respectively) with smaller increases in the biliary output of phospholipid (18% and 45%) and bile acid (26% and 14%). Diosgenin treatment increased serum cholesterol by 29% and increased the biliary output of cholesterol, phospholipid and bile acid by 800%, 10% and 45%, respectively. Thus, both agents increased the cholesterol saturation of bile (100% by niacin, 500% by diosgenin). Cholesterol and phospholipid in fistula bile from control rats were present in lamellar and micellar forms. Niacin treatment did not alter the physical form of biliary lipids whilst diosgenin caused the appearance of vesicular lipid in fistula bile. Thus, increased biliary secretion of cholesterol explains, at least in part, the hypocholesterolaemic action of niacin. In addition, since aggregation of biliary vesicles is involved in cholesterol gallstone formation in humans, the non-appearance of vesicular material in fistula bile from niacin-treated rats may be of some importance.

Animals↗
PubMed1993

Stability and optimization of canalicular function in hepatocyte couplets.

An enriched preparation of rat hepatocyte couplets was obtained by collagenase perfusion and subsequent elutriation (> 85 per cent couplets and triplets; viability of over 95 per cent). Canalicular secretory activity (the ability to accumulate cholyl-lysyl-fluorescein, CLF) was first apparent after 2 h of culture at 37 degrees C and was present in over 80 per cent of the total population after 5-6 h. This remained almost constant for at least 4 h in both elutriated and directly plated cells. Initial storage of freshly prepared couplets at 4 degrees C for up to 6 h prior to incubation had no adverse effect upon secretory function. Reduction of canalicular secretory activity occurred at a concentration of the hepatotoxic agent menadione (IC50 17 microM) that was lower than that required to induce mild plasma-membrane blebbing (IC50 43 microM). This study has optimized and characterized the canalicular secretory effectiveness and stability of an enriched preparation of hepatocyte couplets, and established the feasibility of studies of toxic agents on hepatobiliary function in a heterogeneous population of hepatocytes. In this preparation other biochemical parameters can be assessed, thus complementing previous techniques using individual couplets.

Animals↗
PubMed1993

A demographic overview of the ageing of First World populations.

The ageing of the UK population, and other similar populations, is now well advanced. The process is probably irreversible and may well be repeated across the globe. It is reasonable to assume that 40-50% of the UK adult population will be over 50 for the foreseeable future, and that the number of people in their 80s and 90s will continue to increase for some decades. Growing awareness of this may well lead to a reinterpretation of the life course with consequent changes in lifestyle and activity. In the past, the main focus of design, both of products and environments, has been the working population. There is clearly an urgent need to direct attention to older sectors of the population, including: fit and active people in retirement; affluent groups in old age; single households; women, who form a majority of the over 50s; and other groups which have been neglected in many work studies.

Journal Article↗
PubMed1993

Activities and products for the Third Age.

Designers, ergonomists and professionals with an interest in ageing were surveyed (by questionnaire) for their opinions and attitudes towards existing and potential products and services for the Third Age. They were also questioned on lifestyle expectations for their own Third Age. There is much work that needs to be done, both by ergonomists, in mapping out the needs of a changed society, and by designers, in building up an understanding of the issues and translating that understanding into guidelines, tools and strategies to underpin design in the future.

Journal Article↗
PubMed1993

Epidermolysis bullosa simplex with mottled pigmentation.

A family in which epidermolysis bullosa simplex and mottled pigmentation are inherited as an autosomal dominant disorder is described. Clinical features include: non-scarring blistering, mainly affecting the limbs, mottled pigmentation, predominantly affecting the trunk and neck, warty hyperkeratotic papules of the palms and soles, small red scaly plaques, and skin atrophy. Histology showed an atrophic epidermis, basal cell lysis and significant colloid body formation in an infant from the family.

Adult↗
PubMed1993

Interaction of incontinentia pigmenti and factor VIII mutations in a female with biased X inactivation, resulting in haemophilia.

We report a female infant born to a mother with incontinentia pigmenti (IP) and a father with haemophilia A, who manifests both disorders. Analysis of peripheral blood DNA from the infant, her mother, and two female relatives with IP showed a highly skewed pattern of X inactivation. Random patterns were observed in the infant's two sisters, who do not have IP and have normal carrier activity of factor VIII. Preferential inactivation of the X chromosome bearing the IP mutation, probably by negative selection, appears to have unmasked the factor VIII mutation on the infant's other X chromosome. This illustrates an unusual mechanism for the manifestation of an X linked disease in a heterozygous female.

Dosage Compensation, Genetic↗
PubMed1993

Characterization of cholecystokinin receptors on the human gallbladder.

BACKGROUND: Several studies examined in vivo and in vitro biologic activity of the human gallbladder in response to cholecystokinin (CCK). However, few studies have demonstrated directly the interaction of CCK with receptors on the human gallbladder, which is responsible for this biologic activity. METHODS: To characterize CCK receptors on human gallbladder tissue, gallbladders were removed from human donor grafts that were being used for liver transplantation. The gallbladders were rapidly frozen and sectioned for measurement of binding of 125I-Bolton-Hunter-labeled-CCK-8 and were cut into strips for in vitro bioassay. RESULTS: Binding of 125I-BH-CCK-8 to human gallbladder was saturable, specific, and dependent on time, pH, and temperature. The binding was inhibited only by cholecystokinin-related peptides including CCK-8 (IC50 10 +/- 1.0 nmol/L) (mean +/- SD), des(SO3) CCK-8 (IC50 0.9 +/- 0.2 mumol/L), and gastrin-17-I (IC50 9.0 +/- 2.0 mumol/L) or specific CCK receptor antagonist L-364,718. Computer analysis of binding of 125I-BH-CCK-8 to gallbladder tissue showed a single class of binding sites with high affinity for CCK-8. Autoradiography localized binding of 125I-BH-CCK-8 only to the smooth muscle layer of the gallbladder. In the bioassay des(SO3) CCK-8 (EC50 1.2 +/- 0.7 mumol/L) and gastrin-17-I (EC50 4.5 +/- 2.4 mumol/L) were 150- and 563-fold less potent than CCK-8 (EC50 8.0 +/- 2.2 nmol/L). The relative potencies of CCK agonists for inhibiting binding of 125I-BH-CCK-8 agreed closely with their relative potencies for causing gallbladder contraction. The dose-response curve for CCK-8 alone to induce gallbladder contraction was not significantly different from those caused by CCK-8 plus 1 mumol/L tetrodotoxin or 1 mumol/L atropine. CONCLUSIONS: These results characterized the CCK receptors on smooth muscle of human gallbladder as sulfate dependent and causing gallbladder contraction.

Autoradiography↗
PubMed1993

Pharmacoepidemiology of adverse drug reactions in hospitalized patients with human immunodeficiency virus disease.

To evaluate the incidence, characteristics, and risk factors of adverse drug reactions (ADRs) in patients with human immunodeficiency virus (HIV) disease, we conducted was a prospective observational study of inpatients with HIV disease. The study was conducted in a public teaching hospital affiliated with the University of California, San Francisco. We reviewed daily the hospital records of all eligible inpatients throughout their hospitalization for potential ADRs. Potential ADRs were independently evaluated by two of the authors with regard to the extent of their causal association(s) with implicated drug(s) using a previously validated algorithm. Type (A, augmented; B, bizarre) and severity (mild, moderate, severe) were also evaluated. Among 495 patient admissions involving 390 eligible patients, 173 potential ADRs were identified, of which 118 (68.2%) had a probable or definite causal relationship to the implicated drugs. These probable or definite ADRs occurred among 79 (20%) eligible patients; 82 ADRs (69.5%) were classified as augmented (type A) and 36 (30.5%) were classified as bizarre (type B) reactions. Skin rash was the most frequent (17%) ADR encountered. Of the medications causing ADRs, 70% were antimicrobial drugs. Significant independent risk factors for developing ADRs included advanced stage of HIV disease, intake of a greater number of medications, and longer hospital stay. A high percentage of patients with HIV disease developed ADRs. Skin rash was the single most common kind of ADR. Advanced stage of illness and prolonged drug exposure were the only risk factors for ADRs.

Adult↗
PubMed1992

Advanced computer programs for drug dosing that combine pharmacokinetic and symbolic modeling of patients.

In this paper, we describe our design for advanced drug dosing programs that "reason" using a combination of Bayesian pharmacokinetic modeling and symbolic modeling of patient status and drug response. Our design is similar to the design of the Digitalis Therapy Advisor program, but extends this previous work by incorporating a Bayesian pharmacokinetic model, performing a "meta-level" analysis of drug concentrations to identify sampling errors and changes in pharmacokinetics, and including the results of this analysis in reasoning for dosing and therapeutic monitoring recommendations. The design has been implemented in a program for aminoglycoside antibiotics called Aminoglycoside Therapy Manager. The program is user-friendly and runs on low-cost general-purpose hardware. The initial validation study showed that the program was as accurate in predicting future drug concentrations as an expert using commercial Bayesian forecasting software and that its dosing recommendations were similar to those of an expert.

Aminoglycosides↗
PubMed1992

A phase II study of sulofenur (LY186641) in gastric cancer.

Sulofenur is a novel diarylsulfonylurea with proven anti-tumor activity in murine tumor models. In this phase II study in patients with advanced gastric or gastroesophageal adenocarcinoma, 17 patients were treated with sulofenur orally at 700 mg/m2 for 14 days every 3 weeks. No tumor responses were seen. The main toxicities were anemia, methemoglobinemia and abnormalities in liver function tests. These toxicities precluded dose escalation. However, plasma levels of sulofenur, and its hydroxy and keto metabolites were probably insufficient to exert anti-tumor effect in comparison with data from murine studies. Further structure-activity studies are warranted.

Adenocarcinoma↗
PubMed1992

The psychodynamics of the STD clinic: secrecy, splitting and isolation.

We introduce the idea of a professionally isolated and apparently disconnected agency. We describe how health professionals working in settings with good multi-agency links may not recognize the effect of the isolated agency system on the presentation of problems. In particular, we describe the setting of the Sexually Transmitted Diseases clinic (STD) in which confidentiality can be turned into secrecy by the patients at the service of their denial of the seriousness of their problems. The isolation of the STD clinic as an agency resonates with the patients' isolation from their own feelings and emotional contact with people. It also isolates the professional and the therapeutic network. By way of clinical examples, we describe how this may deskill the staff and lead to dangerous situations.

Adult↗