EFFECTS OF VARIOUS CYTOCHROME P-450 INDUCERS ON TESTOSTERONE METABOLISM AND SEVERAL MONOOXYGENASE ACTIVITIES IN SPRAGUEDAWLEY (SpD), HIGH ALCOHOL SENSITIVITY (HAS) AND LOW ALCOHOL SENSITIVITY (LAS) RATS

Hydroxylation of testosterone (TST) has been shown to be regio-and stereo-specific for a number of cytochrome P-450 isoenzymes.Three rat lines [Sprague-Dawley (SpD), high alcohol sensitivity(HAS) and low alcohol sensitivity (LAS)] were tested for thisenzymatic specificity after treatment with phenobarbital, clofibrate,3-methylcholanthrene and pregnenolone-16-carbonitrile. Thesecompounds are known to induce cytochrome P-450 2B, 4A, 1A and3A1. respectively, in the rat. Induction efficiency was establishedby using the usual enzyme activities specific for these P-450s(pentoxyresorufin, lauric acid, ethoxyresorufin and nifedipineoxidase). Five mono hydroxylated TST metabolites were separatedusing a sensitive HPLC procedure. The hydroxylation of TST wasfound to be significantly different between the lines even inthe uninduced state. The formation of the metabolites of TST,hydroxylated on 2 or 7 or 16 positions and oxidated on carbon17 (4), was found to be significantly increased in SpD ratswhen compared with the HAS-LAS lines (P < 0.0001 in eachcase). When the HAS-LAS lines were compared, the quantity of2 and 16 hydroxylated metabolites was found to be significantlylower in LAS rats (P < 0.05). These differences persisted,although in the opposite direction, after 3-methylcholanthrene(P < 0.01 for both 2 and 16) and phenobarbital induction(P < 0.01 for 2). In conclusion, large differences in TSThydroxylation were found between the SpD and HAS-LAS rats whilemore subtle differences were found between the more closelyrelated HAS-LAS lines especially after phenobarbital and 3-methylcholanthreneadministration as confirmed by our enzyme activity results.The above differences in steroid metabolism between HAS andLAS rats may help to explain their contrasting sensitivitiesto alcohol.     

A feasible model for prevention of functional decline in older home-dwelling people--the GP role. A municipality-randomized intervention trial

Background. Danish municipalities are required by state lawto offer two annual home visits to all non-disabled citizens75 years. Visits are primarily carried out by district nurses.GPs are rarely directly involved. Objective. To evaluate the effects of offering an educationalprogramme to home visitors and GPs on mortality, functionalability and nursing home admissions among home-dwelling olderpeople. Methods. Design: Municipality pair-matched randomized trial. Setting: Danish primary care. Subject: 2863 home-dwelling 75-year-olds and 1171 home-dwelling80-year-olds living in 34 municipalities. Intervention: Home visitors received regular education for aperiod of 3 years. In nine of 17 intervention municipalities,GPs participated in one small group training session duringthe first year. Main outcome measures: Mortality, functional ability and nursinghome admission during 4 years of follow-up. Results. Intervention was not associated with mortality. Homevisitor education was associated with reduction in functionaldecline among home-dwelling 80-year-olds after the three interventionyears in municipalities where GPs accepted and participatedin small group-based training. Effects did not persist afterthe intervention ended. When analyses were restricted to baselinenon-disabled persons, intervention was associated with beneficialeffects on functional ability after three intervention yearsamong 80-year-olds, regardless of education was given to homevisitors alone or to visitors and GPs. Nursing home admissionrates were lower among the 80-year-olds living in the interventionmunicipalities. Conclusion. A brief, practicable interdisciplinary educationalprogramme for primary care professionals postponed functionaldecline in non-disabled 80-year-old home-dwelling persons. Keywords. Education, municipality intervention, older people, preventive home visits, primary care.     

DETERMINATION OF PLASMA {alpha}-GLUTATHIONE-S-TRANSFERASES IN CHRONIC ALCOHOL ABUSERS: RELATIONSHIP WITH ALCOHOL INTAKE AND LIVER INVOLVEMENT

-Gluthathione-S-transferascs (-GSTs) are enzymes involved inthe cellular detoxifying processes; elevated circulating -GSTsactivity is considered to be an early index of liver damage.Glutathione (GSH) is the substrate for -GST action. The aimsof our study were: (1) to evaluate plasma GSH levels and -GSTactivity in chronic alcohol abusers with or without liver cirrhosis;(2) to define the relationship between these two biochemicalparameters; (3) to establish their clinical relevance in patientswith alcohol abuse and/or liver damage. We studied 69 subjects(18 healthy subjects and 51 chronic alcohol abusers: 29 withoutliver cirrhosis and 22 with). Plasma -GST activity was determinedon baseline samples and every following day for a total of 10days in five alcoholics by HEPKIT (Alpha-Biotech, Biotrin International,Dublin, Ireland). GSH was determined on all subjects' baselinesamples by fluorescent high-performance liquid chromatography.Alcohol intake was evaluated in all patients by determiningblood-alcohol concentrations. Significant increases in plasma-GSTs were observed in 9/29 (31%) alcoholics and 3/22 (13.6%)cirrhotics irrespective of their alcohol intake. GSH was significantlylower than normal values (P < 0.001) in all alcoholics withor without cirrhosis (controls 10.4 ± 4.8; alcoholicswithout cirrhosis 3.9 ± 1.4; alcoholics with cirrhosis3.3 ± 1.6). No correlation was observed between plasma-GST and GSH levels. Our data indicate that: (1) -GST activitydoes not correlate with GSH levels in the plasma; (2) -GSTsdo not have clinical relevance as markers of recent alcoholintake; (3) in cirrhotics, -GST does not provide more informationthan other liver function tests. However, plasma -GST determinationmay be useful in selecting a subgroup of alcoholics in whomroutine biochemical markers of liver damage are within referenceranges.     

Predictors of cardiovascular health knowledge among suburban cable TV subscribers and non-subscribers

This study focused on how social-psychological and demographicfactors combined to predict information-holding about cardiovasculardisease prevention among subscribers and non-subscribers toa suburban Midwest cable television system. Data come from oneof three education communities of the Minnesota Heart HealthProgram, a research and demonstration project to reduce communitylevels of heart attack and stroke. A principal component factoranalysis of the total sample (N = 635) extracted two factorsfrom variables operationalizing involvement, self-efficacy andsalience: ‘orientation to health behavior change’,and ‘orientation to disease consequences’. Separatefactor analyses for non-subscribers (N = 228) and subscribers(N = 407) showed a similar factor structure for the former,but the addition of a ‘transitional orientation’factor for the latter characterized by less orientation to healthbehavior change, but greater awareness of increasing informationabout heart disease prevention. These factors together withvariables of gender, age, education, occupation, family compositionand television use were entered into multiple regression analysesfor the total sample (P 0.001), and separately for subscribers(P 0.01) and non-subscribers (P 0.01). In general, gender,education and age emerged as significant predictors with healthorientation and television exposure marginally predictive amongcable-subscribers only.     

Cost-Effectiveness of Acupuncture in Women and Men With Allergic Rhinitis: A Randomized Controlled Study in Usual Care

To assess quality of life and cost-effectiveness of additionalacupuncture treatment for allergic rhinitis, patients were randomlyallocated to 2 groups; both received usual care, but one groupreceived an additional 10 acupuncture sessions. Quality of life(according to the SF-36 Health Survey), and direct and indirectcosts, were assessed at baseline and after 3 months, and theincremental cost-effectiveness ratio of acupuncture treatmentwas calculated. This German study (December 2000–June2004) involved 981 patients (64% women, mean age 40.9 years(standard deviation, 11.2); 36% men, mean age 43.2 years (standarddeviation, 13.0)). At 3 months, quality of life was higher inthe acupuncture group than in the control group (mean PhysicalComponent Score 51.99 (standard error (SE), 0.33) vs. 48.25(SE, 0.33), P < 0.001; mean Mental Component Score 48.55(SE, 0.42) vs. 45.35 (SE, 0.42), respectively, P < 0.001).Overall costs in the acupuncture group were significantly higherthan those in the control group (Euro (; 1 = US $1.27)763, 95%confidence interval: 683, 844 vs. 332, 95% confidence interval:252, 412; mean difference 432, 95% confidence interval: 318,545). The incremental cost-effectiveness ratio was 17,377 perquality-adjusted life year (women, 10,155; men, 44,871) andwas robust in sensitivity analyses. Acupuncture, supplementaryto routine care, was beneficial and, according to internationalbenchmarks, cost-effective. However, because of the study design,it remains unclear whether the effects are acupuncture specific. acupuncture; cost-benefit analysis; economics; quality of life; rhinitis, allergic, perennial; rhinitis, allergic, seasonal     

Health Effects among Workers Involved in the Manufacture of Hexachlorocyclohexane

Forty-five male workers exposed to hexachlorocyclohexane (HCH)during its manufacture were studied and compared with 22 matchedcontrols. Twenty-one of the exposed workers worked in packagingand manual transport of HCH. Twenty-four other exposed workerswere plant operators. Exposure was mainly through skin. Results indicate that the neurological symptoms reported weredue to recent exposure to HCH and were related to the intensityof exposure. An increase in leucine aminopeptidase, ornithine carbamyl transaminase,5'nucleotides and immunoglobulin M levels among the exposedworkers is suggestive of some degree of liver damage. A significantincrease in total blood HCH and its , ß and isomerswas also observed in these workers. In spite of pronounced exposureto the , ß and isomers of HCH, signs of severe healthimpairment were not observed. Further biological monitoringneeds to be carried out among such workers exposed to HCH. Requests for reprints should be addressed to: Dr S. K. Nigam, National Institute of Occupational Health, Meghani Nagar, Ahmedabad-380 016, India     

The volume of the liver in patients correlates to body weight and alcohol consumption

The measurement of liver volume has gained practical use inrelation to liver transplantation (Kawasaki et al., 1993). Livervolume may also relate to the many metabolic processes in whichthe liver is engaged (Homeida et al., 1979; Marchesini et al.,1988; Murry et al., 1995; Reichel et al., 1997; Kwo et al.,1998; Andersen et al., 1999). The present study was undertakento measure liver . . . [Full Text of this Article]FOOTNOTESREFERENCES     

GENETIC POLYMORPHISM OF APOLIPOPROTEIN E IN CAUCASIAN ALCOHOLIC CIRRHOTICS

Steatosis is the most common although inconstant hepatic lesioninduced by chronic alcohol consumption. Alcoholic cirrhosisis found in only 20 to 30% of chronic alcohol misusers, whichpoints to the influence of both environmental and genetic factors.Apolipoprotein E (apo E) presents an important polymorphismwith three common alleles, 4, 3 and 2. Its modulation role ontriglyceride-rich lipoproteins and cholesterol-containing lipoproteinsis linked with its interaction with cellular specific receptors.This work aims at studying a possible correlation between apoE polymorphism and alcoholic cirrhosis. The three common alleleswere identified by enzymatic amplification (PCR) of genomicDNA from blood samples and analysis of restriction profiles.The distribution of alleles and genotypes was performed in 35Caucasian cirrhotic patients (medium age 57 years) and comparedwith the usual distribution of apo E phenotypes in EuropeanCaucasian populations. The results show lower 4 and 2 allelefrequencies and higher 3 allele frequency in Caucasian alcoholiccirrhotics.     

Consumption of Care Among Problem Drinkers in a Small Industrial Town in Sweden

Romelsj A Consumption of care among problem drinkers in a smallindustrial town in Sweden. Family Practice 1988; 5: 271–277. A study of visits to general practitioners, district nurses,occupational health doctors, social services and inpatient careduring one year was conducted for all 282 male and 30 femaleproblem drinkers identified from various registers in a Swedishindustrial town. The 4.5% male problem drinkers aged 20 to 79years accounted for 13.8% of visits to general practitioners,15.3% of stays in somatic departments, 74.1% of stays in psychiatriccare, and over 50% of visits to the social services by malesin those ages. Care consumption by the problem drinkers wasfor both sexes highest among young people. Data about alcoholproblems at any time could be found in 42% of the records formale problem drinkers, while 21% were given a diagnosis of alcoholismby their general practitioner. The problem drinkers were givena great variety of diagnoses. The results emphasize that allpatients should be asked about alcohol habits and that educationand programmes for prevention and treatment should be organizedby primary care together with other relevant parties.     

Determination of ethyl glucuronide in hair samples

Ethyl glucuronide (EtG) is a non-volatile, water-soluble, stable-upon-storage,direct metabolite of ethanol and can be detected in body fluidsand tissues (and also in post-mortem material) for an extendedtime period after the complete elimination of alcohol from thebody (Alt et al., 1997; Schmitt et al., 1997; Seidl et al.,1998; Wurst et al., 1999a,b). The aim of the present Letteris to emphasize . . . [Full Text of this Article]FOOTNOTESREFERENCES     

{alpha}-Amylase hypersensitivity in non-exposed millers

Occupational hypersensitivity to -amylase among bakers and workersin the pharmaceutical industry has been described. We presentthe results of skin tests and in vitro methods used to assess-amylase sensitivity in 259 millers. There was no occupationalcontact with the enzyme in this population. Positive skin teststo this allergen were obtained in 16 subjects (6.18 per cent),specific IgE values were found in seven subjects (2.7 per cent),specific IgG was detected on 45 workers (17.37 per cent) andhigh values for IgG (>2.5 absorbance units) were found in12 subjects (4.63 per cent). Furthermore, specific IgE and IgGcould be determined in several sera by immunoblotting. All these facts suggested that millers were sensitized to Aspergillusoryzae -amylase, although the allergen was not used by theseworkers. A cross-reaction cannot be excluded; however, it isthe authors' opinion that wheat or wheat flour is a naturalsubstrate for fungi and that the moulds that grow on cerealsor cereal-derived by-products need to secrete amylases to supporttheir own development. Hence the workers may be indirectly sensitizedto amylases.     

BEHAVIORAL THERMOREGULATION IN THE RAT FOLLOWING THE ORAL ADMINISTRATION OF ETHANOL

To assess if ethyl alcohol (ethanol) causes a reduction in theset-point for control of body temperature, behavioral thermoregulatoryresponses in the Fischer rat were measured following a singleoral administration of ethanol. In a preliminary study, fiverats were given 3.0 g/kg ethanol dissolved in saline (20%; v/v)by gavage and placed in a longitudinal temperature gradientfor 2 hr. The temperature gradient permitted the rats to behaviorallythermoregulate (i.e. select a thermal preferendum). The selectedambient temperature (T) in the temperature gradient was notablylower during the initial and final stages of the test periodwhen compared to the response of rats administered similar volumesof saline. Colonic temperature upon removal from the gradientwas approximately 1.0°C below that of the saline-treatedanimals. In a followup study, rats were placed in the temperaturegradient for 1 hr for accommodation purposes. The rats werethen gavaged with 0,1.0 or 3.0 g/kg ethanol and placed backin the gradient for another 2 hr. Selected T was significantlyreduced in the 3.0 g/kg group during the second hour post-ethanolexposure. The 1.0 g/kg dosage had little effect on selectedT. As in the preliminary study, the colonic temperature of therats in the follow up study given 3.0 g/kg was 1.0°C belowthat of the control at 2 hr post-injection. Because the 3.0g/kg treated animals were significantly hypothermic and selectedcooler Ts in the temperature gradient, it was concluded thatethanol exerted a lowering of the set-point for control of bodytemperature.     

Antibiotic use in upper respiratory tract infections in New Zealand

Upper respiratory tract infections (URTIs) are a common reasonfor presentation to general practitioners. The current studyused computerised consultation records of 100 222 patients from17 general practices in New Zealand for the 12-month period1 July 1991–30 June 1992. URTIs were noted in 8.9% ofall consultations: 44.1% of cases were children aged less than10 years. Females presented more frequently than males for allages above five years. Fifteen different antibiotics were prescribedfor URTIs, but in 22.5% of cases no antibiotic was prescribed.There was no statistically significant difference in the likelihoodof a successful outcome with or without antibiotic therapy (²= 0.76, P > 0.05). The treatment failure profile of someantibiotics highlights the need for more prescriber education,especially as the range of medications available for generalpractitioner prescribing increases.     

EFFECTS OF THIAMINE DEFICIENCY ON BRAIN METABOLISM: IMPLICATIONS FOR THE PATHOGENESIS OF THE WERNICKE-KORSAKOFF SYNDROME

Chronic alcoholism results in thiamine deficiency as a consequenceof inadequate dietary intake and of impaired absorption of thevitamin. In addition, there is evidence to suggest that alcoholreduces thiamine phosphorylation to thiamine pyrophosphate (TPP)in brain. TPP is a cofactor for the pyruvate dehydrogenase complex(PDHC), -ketoglutarate dehydrogenase (KGDH) and transketolase(TK), three enzymes involved in cerebral glucose and energymetabolism. Pyrithiamine-induced thiamine deficiency in therat results in early, selective, reversible reductions of KGDHin brain; PDHC activities are unaffected. Reductions of KGDHare accompanied by decreased aspartate, glutamate and GABA andby concomitantly increased alanine in the brain of thiamine-deficientanimals. It is suggested that decreased KGDH, rather than decreasedPDHC constitutes ‘the biochemical lesion’ in thiaminedeficiency encephalopathy first enunciated by Peters in the1930s. If sufficiently prolonged and severe, thiamine deficiencyresults in brain cell death. Possible mechanisms involved includecompromised cerebral energy metabolism and focal accumulationof lactate, both of which could result from decreased activitiesof KGDH. In addition, it is proposed that brain cell death insevere thiamine deficiency may result from excessive releaseof excitotoxic amino acids. Comparable mechanisms could be involvedin the cell death and in the pathogenesis of the thiamine-unresponsivesymptoms of the Wernicke-Korsakoff Syndrome in humans     

Detection times for urinary ethyl glucuronide and ethyl sulfate in heavy drinkers during alcohol detoxification

Aims: Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are conjugatedethanol metabolites formed in low amounts after alcohol consumption.Compared with ethanol, EtG and EtS are excreted in urine fora prolonged time, making them useful as sensitive alcohol biomarkers.This study determined the detection times for EtG and EtS inalcoholic patients undergoing alcohol detoxification. Methods:Alcohol-dependent patients (n = 32) with an initial alcoholconcentration 1 g/L based on breath testing were followed duringdetoxification. Urine samples for determination of EtG, EtS,ethanol and creatinine were collected on admission to the hospitaland thereafter once daily for several days. EtG and EtS measurementswere performed by liquid chromatography-mass spectrometry (LC-MS)and EtG also using an immunochemical assay (DRI-EtG EIA, ThermoFisher/Microgenics).Results: The detection time for urinary EtG was weakly correlated(r = 0.434, P = 0.013) with the initial alcohol concentration(range 1.0–3.4 g/L). For EtG, the individual time rangeuntil return to below the applied cut-off limit (<0.5 mg/L)was 40–130 h (median 78) with a similar time course observedfor EtS. After correction for urine dilution, the time untilan EtG/creatinine ratio <0.5 mg/g was 40– 90 h (median65). The detection times after an estimated zero ethanol concentrationwere 30–110 h (median 66) for EtG and 30– 70 h (median56) for EtG/creatinine. The EtG results by LC-MS and the immunoassaywere in good agreement. Conclusions: During alcohol detoxification,EtG and EtS remained detectable in urine for several days. Thedetection times showed wide inter-individual variations, alsoafter adjusting values for urine dilution and to the estimatedtimes for a completed ethanol elimination.     

Skin-prick tests for hypersensitivity to {alpha}-amylase preparations

Twenty-five asthmatic subjects with suspected -amylase hypersensitivitywere studied by skin-prick tests, a capture ELISA, immunoblottingand bronchial provocation tests. At the same time, differentamylases were analysed by SDS-PAGE and immunoblotting usinga polyclonal rabbit antiserum. Eight patients showed a positivebronchial response to amylase. Seven of them had positive skin-pricktests, with this method being the most sensitive approach fordiagnosis. However, in four cases, skin tests were also positivealthough the patients had a negative provocation test, thusdemonstrating that skin tests are not specific. ELISA and blottingshowed similar results in terms of sensitivity and specificity.The enzymes used by the workers included several antigens besides-amylase. The rabbit antiserum to -amylase detected a proteinin a wheat flour extract. In one case, the IgE antibodies werespecific only for a contaminant of lower molecular weight thanamylase. These facts suggest that proteins from the culturemedium could be responsible for some cases of amylase hypersensitivity,making the diagnosis difficult. The presence of amylase in anotherenzymatic extract, a protease produced by Aspergillus oryzae,was proved by means of skin tests and immunoblotting, thus demonstratingthe allergenic properties of this enzymatic preparation.     

Waist circumference home measurement--a device to find out patients in cardiovascular risk

Background: New strategies are needed to prevent the globalepidemic of diabetes and subsequent rise in cardiovascular diseases.We describe a community-based, two-stage screening strategyusing home waist circumference measurement and a risk factorquestionnaire as a primary screening tool. Methods: We maileda tape for measurement of waist and a risk factor questionnaireto every inhabitant aged 45–70 years living in the ruraltown of Harjavalta in Finland. Thereafter we performed an oralglucose tolerance test, anthropometric variables and blood pressureof subjects having at least one risk factor for type 2 diabetesor cardiovascular disease. People with previously known diabetesor vascular disease were excluded. Results: Seventy-three percent(2085/2856) of the invited inhabitants participated, and 84%of the respondents had at least one pre-specified risk factor.Waist circumference 80 cm in women and 94 cm in men (n = 1168),positive metabolic syndrome criteria of the International DiabetesFederation (n = 681) or the Finnish Diabetes Risk Score questionnaire12 points (n = 697) identified 95, 92 and 63% of the new casesof type 2 diabetes and 84, 75 or 62% of pre-diabetes, respectively.Conclusion: The International Diabetes Federation criteria forelevated waist circumference are very sensitive but lack specificityin diagnosing glucose disorders. The criteria for metabolicsyndrome and the Finnish Diabetes Risk Score questionnaire aremore efficient tools for the selection of patients for furtherrisk stratification in general practise.     

Alcohol exposure in utero and breast cancer risk later in life

Since the pioneering work of Hiatt and Bawol (1984), there hasamassed a considerable amount of evidence that moderate-to-heavyalcohol consumption increases risk of breast cancer in women(Willett et al., 1987; Longnecker, 1999). A plausible mechanismis by alcohol's effects on circulating hormone levels. Alcoholadministration has been reported to increase circulating oestradiollevels in pre-menopausal women (Reichman et al., 1993); theevidence is mixed in . . . [Full Text of this Article]FOOTNOTESREFERENCES     

SERUM {gamma}-GLUTAMYL-TRANSPEPTIDASE ISOFORMS IN ALCOHOLIC LIVER DISEASE

-Glutamyltranspeptidase (GT) appears in serum in multiple forms;their significance and clinical utility in hepatobiliary andpancreatic diseases are still a matter of controversy. Electrophoreticseparation of the multiple forms of GT on agarose gel was performedin 20 alcoholic patients (six with cirrhosis and 14 with fattyliver) and the results compared with those obtained in 50 healthyvolunteers, 43 patients affected with chronic hepatitis C, 36patients with posthepatitic cirrhosis and in 52 epileptic patientson long-term anti-epileptic medication. Multiple forms of GTwere separated into several bands (up to 11), labelled 0a, 0b,la, lb, 2a, 2b, 2c, 3a, 3b, 4a, 4b. In the alcoholic patientsnine fractions were detected, and the electrophoretic patternobserved was significantly different from that observed in healthyvolunteers and in patients with chronic hepatitis C or posthepatiticcirrhosis. No differences were observed in the electrophoreticpatterns in the alcohol abusers and epileptic patients. In alcoholicpatients significant differences were observed in the electrophoreticpatterns in relation to the degree of liver injury; the electrophoreticpatterns in patients with alcohol-related cirrhosis and posthepatiticcirrhosis differed significantly. The separation of multipleforms of GT has high sensitivity and good reproducibility. Itmay be proposed as a complementary test in the diagnosis ofalcoholic liver disease.