The Nominal Group Technique: A Research Tool for General Practice?

Qualitative methods are increasingly recognized as valuable,yet practitioners face difficult decisions in their choice ofmethod and the process of analysis. The nominal group techniquecombines quantitative and qualitative data collection in a groupsetting, and avoids problems of group dynamics associated withother group methods such as brainstorming, Delphi and focusgroups. Idea generation and problem solving are combined ina structured group process, which encourages and enhances theparticipation of group members. The stages involved in conductinga nominal group are described, and practical problems of itsuse in a health care setting are discussed with reference toa study of the priorities of care of diabetic patients, carersand health professionals. Some potential applications of thetechnique in audit and exploratory research are also outlined.     

Modification by Nickel of Instrumental Thermoregulatory Behavior in Rats1

Modification by Nickel of Instrumental Thermoregulatory Behaviorin Rats. WATANABE, C, WEISS, B., COX, C, AND ZIRIAX, J. (1990).Fundam. Appl. Toxicol. 14, 578–588. The effects of NiCl₂on the colonic temperature and thermoregulatory behavior (TRB)of rats were examined. TRB was evaluated in an instrumental(operant) setting in which rats were required to press a leverto obtain convectional heat (SEEK) or to avoid heat (ESCAPE).Orthogonal polynomial regression was used to describe the responsepatterns in both the SEEK and ESCAPE situations. Two milligramsper kilogram of Ni (ip) caused rapid, transient hypothermiaat an ambient temperature of 21°C. When given access toheat reinforcement, rats responded for heat at a lower rateimmediately after 2 or 5 mg/kg of Ni (up to 5–15 min)than after saline. Subsequently, response rates rose 30 minor more after Ni injection. A converse pattern was found withthe heat escape situation. These observations, confirmed bytwo contrasting procedures, indicate that the changes were thermoregulatoryin nature and cannot be explained by nonspecific sup-pressiveor excitatory effects of Ni. They further suggest that Ni-inducedhypothermia results from an altered body temperature set point.The subsequent reversal in behavior probably arises from a directaction of Ni on autonomic effector mechanisms. The origin andbiological significance of these findings require further investigation.Physical requirements and response topography are discussedas critical variables in the interpretation of experiments requiringsimilar responses under different ambient temperatures.     

FLUMAZENIL IN ALCOHOL WITHDRAWAL: A DOUBLE-BLIND PLACEBO-CONTROLLED STUDY

The purpose of the present study was to study -aminobutyricacid (GABA)-A receptor function in alcohol-dependent subjectsduring withdrawal, using the benzodiazepine antagonist flumazenil.In particular, we wanted to examine the hypotheses that an endogenousinverse agonist ligand at the GABA-A benzodiazepine receptor(GBzR) is active during withdrawal (in which case flumazenilshould be anxiolytic), or whether chronic alcohol intake resultsin a shift in sensitivity of the receptor in the inverse agonistdirection (in which case flumazenil should be anxiogenic). Resultsfrom 15 alcohol-dependent subjects in a double-blind placebo-controlledcross-over study showed that flumazenil was neither anxiolyticnor anxiogenic, although withdrawal scores were reduced duringthe course of the study. The fact that flumazenil was not anxiogenic,as it is in panic disorder, suggests that the GBzR is functioningdifferently in these two clinically similar conditions.     

Inhibition of 3,3',4,4',5-Pentachlorobiphenyl-Induced Chicken Embryotoxicity by 2,2',4,4',5,5'-Hexachlorobiphenyl

3,3',4,4',5-Pentachlorobiphenyl (pentaCB) caused a dose-dependentinduction of chicken embryolethality, malformations, edema,and liver lesions at doses ranging from 0.5 to 12.0 µg/kg.In contrast, no embryotoxicity was observed after treatmentwith 10, 25, or 50 mg/kg 2,2',4,4',5,5'-hexaCB. In eggs cotreatedwith 2.0 µ/kg, 3,3',4,4',5-pentaCB plus 10, 25, or 50mg/kg 2,2',4,4',5,5'-hexaCB, there was significant protectionfrom 3,3',4,4',5-pentaCB-induced embryo malformations, edema,and liver lesions, whereas no inhibition of embryolethalitywas observed. These results further extend the response-specificnonadditive interactions of binary mixtures of polychlorinatedbiphenyls (PCBs) and should be considered in the developmentof approaches for hazard assessment of PCB mixtures and relatedcompounds.     

Can One be a Good Doctor and have a Sexual Relationship with One's Patient?

This paper presents a qualitative exploration of social andsexual contact between general practitioners and their patients.Social contacts have been implicated in the development of sexualrelationships between members of the mental health professionsand their patients. However, there has been little examinationof the implications for general practitioners. Six focus groupswere conducted by teleconference with New Zealand general practitioners.Participant anonymity was maintained. Questions focused on issuesof social and sexual contact in general practice. Major themeswere extracted from the data. A range of definitions of ‘patient’,‘sexual contact’ and ‘social contact’were offered by the participants which demonstrated that ‘greyareas’ existed for them in relation to social and sexualrelationships with patients. Mandatory reporting of colleaguesfor alleged sexual misconduct was not supported, informal mechanismsbeing preferred. General practitioners need to be aware of potentialboundary violations in their practice. These issues are alsoimportant to address in the teaching of medical students, continuingmedical education, and in the development of appropriate guidelinesfor general practice.     

Subchronic Inhalation Toxicity Studies with Hydrochlorofluorocarbon 123 (HCFC 123)

Hydrochlorofluorocarbon 123 (HCFC 123) is one of the chemicalsbeing considered as a replacement for the chlorofluorocarbons.Four subchronic inhalation toxicity studies from 1 to 3 monthsin duration have been conducted with HCFC 123. One study utilizedrats and dogs, while the others were limited to rats only. Theexposure levels have ranged from 300 ppm up to 20,000 ppm. Althoughthe studies were conducted over a 14-year period, the resultswere consistent. In all studies, increases in liver weightswere seen at 1000 ppm and above; additionally, one showed thiseffect at 500 ppm. Histopathological findings were minimal,consisting primarily of focal necrosis in the liver of the dogsat 10,000 ppm. Induction of peroxisomal activity, lowering ofserum cholesterol and triglyceride levels, and an increase inurinary fluoride levels were also seen. The 4-hr LC₅₀ in therat has been reported as 35,000 ppm. At 20,000 ppm for 6 hr,the total daily dose on a concentration times time basis isalmost equal to the LC₅₀ yet, in the 4-week study, with 20 exposuresat this level, there was no mortality or even marked signs oftoxicity. There appeared to be no evidence for cumulative toxicityfrom multiple exposures in these studies. Overall, HCFC 123appears to have a low level of toxicity by the inhalation route.     

Reproductive Toxicity of Butylated Triphenyl Phosphate and Tricresyl Phosphate Fluids in F344 Rats

The effects of tricresyl phosphate (TCP) and butylated triphenylphosphate (BTP)-based hydraulic fluid on reproduction were studiedin F344 rats using a modification of the National ToxicologyProgram's Continuous Breeding Protocol. Groups of breeding pairsreceived single daily oral doses of an equal volume of either0, 0.6, 1.0 g BTP/kg or 0.4 g TCP/kg in sesame oil or 1.7 gneat BTP/kg for up to 135 days. A naive control group allowedto breed, but not dosed or handled daily, demonstrated thatdaily dosing and handling of the rats had no effect on reproduction.The fertility index and number of litters born were significantlydecreased in rats exposed to 1.0 and 1.7 g BTP/kg and 0.4 gTCP/kg. The number of pups per litter was significantly decreasedin the TCP group. A crossover mating experiment using 0.4 gTCP/kg/day and 1.0 g BTP/kg/day groups, each mated with vehiclecontrols, demonstrated that TCP caused 100% infertility in malerats but did not affect reproduction in females. BTP causeda significant decline in reproduction in female rats characterizedby low mating and fertility indices, decreased number of litters,and abnormal estrous cycles. Fertility was decreased in theBTP-dosed male rats. Both sexes of rats in the crossover experimentwith TCP and BTP had significant decreases in terminal bodyweights and increases in adrenal gland and liver weights. OnlyTCP-dosed male rats had significantly decreased testicular andepididymal weights. TCP-dosed female rats had increased ovarianweights, while BTP-dosed females had significantly lower uterineweights. The results of this study indicate that BTP and TCPare reproductive toxicants in F344 rats.     

Deuterium Isotope Effect on the Metabolism of the Flame Retardant Tris(2,3-dibromopropyl) Phosphate in the Isolated Perfused Rat Liver

The metabolism of tris(2,3-dibromopropyl) phosphate (Tris-BP)was compared with that of completely deuterated Tris-BP (D15-Tris-BP)in an isolated, recirculating rat liver perfusion system inorder to determine the relative quantitative importance of twodifferent biotransformation pathways of Tris-BP: (i) cytochromeP450-mediated metabolism and (ii) GSH S-transferase-mediatedmetabolism. To accomplish this we quantitated the biliary excretionof S-(3-hydroxypropyl)glutathione (GSOH) as a marker metabolitefor cytochrome P450-mediated metabolism and that of S-(2,3-dihydroxypropyl)glutathione (GSOHOH) as a marker metabolite for GSH S-transferase-mediatedmetabolism. Completedeuterium substitution of Tris-BP significantlydecreased the formation of GSOH, whereas there was no effecton the formation of GSOHOH. Because our previous studies showeda large decrease in genotoxicity of D15-Tris-BP compared toTris-BP, the present results support our hypothesis that cytochromeP450-mediated metabolism is responsible for the genotoxic effectsof Tris BP in the rat liver.     

Contractile Responses and Structure of Small Bronchi Isolated from Rats after 20 Months' Exposure to Ozone

Short-term exposure to high concentrations of ozone has beenshown to increase airway responsiveness in normal humans andin all laboratory animal species studied to date. While ourknowledge concerning the pulmonary effects of single exposuresto ozone has increased rapidly over recent years, the effectsof repeated exposures are less understood. The goal of the presentstudy was to determine whether airway responsiveness is increasedafter near-lifetime exposure to ozone. Airway segments representingapproximately eighth generation airways were isolated from Fischer344 rats of both genders that had been exposed for 6 hr perday, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 partsper million (ppm) ozone. Circtimferential tension developmentwas measured in isolated airways in response to bethanechol,acetylcholine, and electrical field stimulation. Responsivenessof the airways to the contractile stimuli was described by theeffective dose or frequency that elicited half-maximum contraction(ED50) and the maximum response. Since ozone exposure is associatedwith remodeling of peripheral airways, smooth muscle area wasdetermined and tension responses were normalized to the areameasurements. Before normalization of tension data to smoothmuscle area, neither the ED50 nor maximum response of smallbronchi to the contractile stimuli was altered after chronicozone exposure. Smooth muscle area was greater in airways isolatedfrom animals that had been exposed to 0.5 ppm ozone. After accountingfor smooth muscle area, maximum responses of the small bronchiisolated from male rats were significantly reduced after 0.12and 0.5 ppm ozone. Although not significant statistically, asimilar trend was observed in airways isolated from female rats.These results suggest that the increase in airway responsivenessassociated with acute ozone exposure does not persist duringnear-lifetime exposure. Although the mechanism responsible forthe adaptation to the effects of 03 on airway responsivenessis unknown, the results indicate that smooth muscle cell functionwas compromised by the chronic exposure. The mechanism(s) responsiblefor mediating this effect and the relevance of these resultsto humans remains to be determined.