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Biomedical subjects

A M Brady

Publications and source records attributed to A M Brady.

12 recordsLinked to original sources

The involvement, understanding and attitudes of dietitians towards research and audit.

AIM: To investigate the involvement of dietitians in research and audit and to assess their understanding of and attitudes towards these activities. METHODS: A postal questionnaire was used to investigate the knowledge, attitude towards and involvement in research and audit of State Registered Dietitians practising in the National Health Service (NHS) in the UK. RESULTS: A response rate of 64% was achieved. Few respondents (15%) were currently involved in research, although more (65%) were currently involved in audit. Involvement in audit rose significantly with increasing grade and managerial responsibility. Dietitians qualifying more recently were more likely to believe that their college training prepared them to undertake research, but felt less confident about undertaking audit. Experience of audit made respondents more confident about auditing their work and improved their belief that they understood audit terminology. Higher grade dietitians were more likely to see audit as an important part of their role than were their more junior colleagues. Understanding of the terms 'research' and 'audit' was poor, although 48% of respondents identified the link between the two activities. Perceived constraints to involvement in research and audit were identified. CONCLUSION: The present level of involvement of dietitians in research and audit activities falls below that recommended in the BDA's (1997a) National Professional Standards for Dietitians Practising in Healthcare. This study identifies factors that influence dietitians' involvement in, understanding of and attitudes towards research and audit and recommends ways of increasing their involvement in these activities.

Adult↗

The oral administration of polysorbate 80 to the immature female rat does not increase uterine weight.

Some xenobiotics display estrogenic activity in in vitro and/or in vivo systems. Previous studies by Gajdova et al. have shown that polysorbate 80 (also known as Tween 80) administered by intraperitoneal injection to neonatal female rats on days 4-7 after birth produced estrogenic effects including earlier vaginal opening, prolongation of the estrus cycle and persistent vaginal estrus. Some of these effects were evident many weeks after cessation of administration of polysorbate 80. The present study has evaluated the estrogenic properties of polysorbate 80 following oral administration, a route of exposure which is more relevant for the consideration of human health hazard. The effects of polysorbate 80 at oral gavage doses of up to 5 g/kg/day for 3 consecutive days on uterine growth of immature female rats, a commonly used in vivo mammalian assay for estrogenic activity, have been determined. Estradiol benzoate administered subcutaneously was used as a positive control and significantly increased uterine weight in this age and strain of female rat (21-23 days, Alpk:APfSD Wistar derived) by up to 4.5-fold above vehicle control values. Polysorbate 80 administered orally to rats had no effect on uterine weight. Thus, intrinsic estrogenic effects of polysorbate 80 reported following its intraperitoneal injection to neonatal 4-day-old female rats are not manifest when it is administered by oral gavage to immature 20- to 22-day-old female rats. This latter route of exposure is of more relevance to human exposure scenarios and these data are, therefore, important in assessing hazard/risk of polysorbate 80 to man.

Administration, Oral↗

Rationale and perspectives on the development of fungicides.

Fungicides continue to be essential for the effective control of plant diseases. New classes of fungicides with novel modes of action are being developed in the 1990s. These include the strobilurins, phenylpyrroles, anilinopyrimidines, phenoxyquinolines, and compounds that trigger defense mechanisms in the plant. For the foreseeable future, new toxophores will be identified through a process of random screening, with natural products representing a rich source of fungicide leads. Progress is being made in the development of high-throughput screens comprised of target enzyme sites or cell-based assays; these techniques will improve the probability of discovery. Following the identification of suitable leads, biorational design is used to optimize specific properties. In vivo glasshouse screens and field trials are expected to remain the dominant methods for characterizing new compounds. Low toxicity to humans and wildlife, low environmental impact, low residues in food, and compatibility with integrated pest management (IPM) programs are increasingly important considerations in the selection of fungicides for development.

Journal Article↗

Management of painful paraneoplastic syndromes.

The majority of patients with advanced malignant disease experience pain, so pain is commonly present in patients with paraneoplastic syndromes. It is rare, however, that the pain itself is a paraneoplastic manifestation of cancer. Usually, the pain in this context is associated with a paraneoplastic syndrome but is not a direct result of that syndrome. Three syndromes in which pain is part of the syndrome and a paraneoplastic manifestation of malignant disease--neuropathy, ganglionitis, and monolitis--have been described in the literature. These syndromes and their management are discussed in this article.

Humans↗

Effects of 2-[1-(ethoxyimino)propyl]-3-hydroxy-5-(2,4,6-trimethylphenyl) cyclohex-2-enone on hepatic haem biosynthesis: species differences in hepatic porphyria.

2-[1-(Ethoxyimino)propyl]-3-hydroxy-5-(2,4,6-trimethylphenyl) cyclohex-2-enone (ETC) is a novel alkyl ketone herbicide. Continuous administration of ETC to mice for 28 days resulted in marked liver enlargement and severe intrahepatic cholestasis. These effects have been shown to result directly from a rapid and marked accumulation of porphyrin in the liver. The porphyrin which accumulates in the liver has been identified as protoporphyrin IX and dose response and time course studies confirm prior inhibition of mitochondrial ferrochelatase as the causal lesion. ETC was a very potent porphyrinogenic compound in mice, with a no-effect level for a single oral dose of 1 mg/kg. Rats and hamsters were insensitive to this type of hepatotoxicity following single oral doses of up to 750 mg/kg or following repeated, and indeed prolonged administration. The sensitivity of different species to ETC-induced porphyria correlated with the effect of ETC on hepatic ferrochelatase activity. The inhibition of ferrochelatase activity and the hepatic porphyria in mice were both found to be readily reversible upon withdrawal of ETC.

Administration, Oral↗

Patterns of care.

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Adolescent↗

The practice patterns of adult oncologists' care of pediatric oncology patients.

The role of the adult oncologists in the area of pediatric cancer treatment previously has been unmeasured. A questionnaire bearing regarding the practice of 447 adult oncologists was administered in June 1991. The membership list of the Association of Community Cancer Centers was used to identify contact oncologists. One hundred thirty-one questionnaires (29.3%) were returned for analysis. The data reveal that 204 patients younger than 21 years of age were treated during the last year in 63 adult oncology practices. Most of these patients were more than 15 years of age. Only a minority (53) were treated in rural practices. In addition, only a minority (27%) of these patients are reported to be enrolled in clinical trials. In addition, adult oncologists appear to regard physiologically mature adolescents (age 16-21 years) as adults. They do not seem to make a distinction between patients 16-21 years old and those older than 21 years.

Adolescent↗

Identification of the proximate peroxisome proliferator(s) derived from di (2-ethylhexyl) adipate and species differences in response.

Identification of the proximate peroxisome proliferator(s) derived from di (2-ethylhexyl) adipate (DEHA) has been achieved using primary hepatocyte cultures derived from different species and cyanide-insensitive fatty acyl CoA oxidase (PCO) as a marker enzyme for peroxisome proliferation. In rat and mouse hepatocytes, the parent compound (DEHA) had no effect on peroxisomal beta-oxidation, but primary metabolites of DEHA, mono (2-ethylhexyl) adipate (MEHA) and 2-ethylhexanol (EH), were approximately equipotent in PCO induction (5-fold at 0.5 mM final concentration). The secondary metabolite of DEHA, 2-ethylhexanoic acid (EHA), was in both species the most potent peroxisome proliferator (25- and 9-fold induction in mice and rats, respectively, at 1 mM final concentration). At 2 mM final concentration a tertiary metabolite of DEHA, 2-ethyl-5-hydroxyhexan-1-oic acid, was less effective in mouse and rat hepatocytes at inducing PCO (15- and 5-fold, respectively). 2-Ethyl-5-oxohexan-1-oic acid and 2-ethylhexan-1,6-dioic acid had little effect (2-3-fold in both rat and mouse hepatocytes). Thus, EHA was identified as the proximate peroxisome proliferator of DEHA and mouse hepatocytes were approximately twice as sensitive as rat hepatocytes to peroxisome proliferation due to MEHA, EH and EHA. We investigated further species differences in response to peroxisome proliferators by using guinea pig and marmoset primary hepatocyte culture. None of the chemicals studied stimulated peroxisomal beta-oxidation in these species up to a final concentration of 2 mM. Higher concentrations lead to cytotoxicity. This lack of sensitivity of guinea pig and marmoset hepatocytes is in agreement with previous studies with di (2-ethylhexyl) phthalate metabolites, suggesting the absence of a threat of hepatocarcinogenic damage to these species and confirming that primary hepatocytes cultures are useful models for investigating the phenomenon of peroxisome proliferation.

Adipates↗

Inhibition of ferrochelatase and accumulation of porphyrins in mouse hepatocyte cultures exposed to porphyrinogenic chemicals.

The ability of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine (EDDC) and griseofulvin to induce porphyria in primary cultures of mouse hepatocytes has been examined. Exposure of cultured mouse hepatocytes to DDC, EDDC or griseofulvin resulted in a marked inhibition of ferrochelatase which was sustained over the 4-day exposure period. Maximal concentrations of DDC (25 microM), EDDC (25 microM) and griseofulvin (25 microM) resulted in 14-fold, 30-fold and 9-fold increases, respectively, in total porphyrin in the culture medium. Analysis of the porphyrins accumulating indicated a predominance of protoporphyrin with all three xenobiotics. Addition of 5-aminolaevulinic acid (ALA) to mouse hepatocyte cultures (10-1000 microM) resulted in much larger increases (up to 164-fold) in porphyrin accumulation in the medium and the porphyrin accumulating was predominantly uroporphyrin. These studies have demonstrated that primary cultures of mouse hepatocytes provide a valid mechanism-based in vitro model of the hepatic porphyrias produced by the dihydropyridines and griseofulvin in mice.

Aminolevulinic Acid↗

Fostering collaboration by understanding physician behavior: the cancer program perspective.

To build collaborative relations with physicians, which are particularly desirable in cancer programs, hospital administrators must first understand the intrinsic differences between the ways physicians and hospital administrators operate. Administrators' failure to understand physicians' behavior can hamper the development of such programs. Relations between physicians and hospitals have traditionally been good, and while hospital administrators and physicians have approached health care from different perspectives, their activities have generally been mutually supportive. Over the last decade, however, health care payment reform has exacerbated differences in hospitals' and physicians' goals and expectations, and these differences have begun to threaten the traditional collaborative relationship between hospitals and physicians. This report is intended for hospital administrators who wish to strengthen their relationships with their physicians and thereby develop a more comprehensive approach to the delivery of cancer care services. It identifies specific physician behavioral tendencies and analyzes their potential impact on the delivery of patient-centered cancer care. It also examines the ways physicians' attitudes and behaviors develop, as well as the reasons physicians may find themselves in conflict with other health care providers. Finally, it reviews current factors affecting physician/hospital relations and suggests ways hospitals and their medical staffs can develop mutually supportive, collaborative activities.

Attitude of Health Personnel↗