Issues in the development of health promotion indicators

The rapid adoption of the concept of health promotion in recentyears, with the corresponding need to monitor health promotionendeavours, raises issues for the development of valid indicatorsof progress. A first step in such development is the differentiationof health promotion indicators from indicators of health status.The former constitute the means or methods to achieve the goalof enhancing health. The two types of indicators should be conceptuallydistinguished. Indicators must be refined, to tap the relevantdimensions of influences on health. Another major issue in thedevelopment of health promotion indicators is the excessivefocus on indicators of personal behaviour. Meaningful indicatorsare needed of the cultural, structural and situational processesthat affect health.     

The Inhalation Toxicology, Genetic Toxicology, and Metabolism of Difluoromethane in the Rat

Difluoromethane (HFC32) is under development as a replacementfor chlorofluorocarbons (CFCs) in some refrigeration applications.It has been evaluated by standard studies of toxicity, developmentaltoxicity, and genotoxicity. In addition, the metabolism anddisposition of HFC32 was investigated and a physiologicallybased pharmacokinetic (PB-PK) model constructed. Inhalationof HFC32 (up to 50,000 ppm) caused no organ-specific effects,but resulted in slight maternal toxicity to the pregnant ratand rabbit and some fetotoxicity to the rat. HFC32 did not sensitizethe heart to adrenaline. The pharmacokinetics of [¹⁴C]difluoromethane(10,000 to 50,000 ppm/6 hr) revealed that about 2.1% of theinhaled HFC32 was absorbed and that steady state blood levelswere achieved within 2 hr and were proportional to dose. Carbondioxide was the major metabolite of HFC32 at all exposure levels.Carbon monoxide was not detected. The in vivo data were usedto validate a PB-PK model to describe the uptake and metabolismof HFC32. Absorption and distribution are adequately describedusing rat blood:air and tissue:air partition coefficients. Metabolism,which was linear across the dose range, was described by a firstorder rate constant (K_f=8.98 hr^–1). Of the absorbed HFC32,about 63% was metabolized at all doses; however, when metabolismwas expressed as a percentage of the inhaled dose it was muchlower, being about 1.4% of the HFC32 entering the airways. Overall,the results indicate that HFC32 is of very low toxicity andshould be an acceptable alternative to CFCs.     

Lack of Peroxisome Proliferation in Marmoset Liver Following Treatment with Ciprofibrate for 3 Years

The effect of treatment of marmosets with ciprofibrate for 3years on activities of hepatic enzymes, hepatic histomorphology,and ultrastructure were investigated. Male and female mar mosetswere dosed with ciprofibrate (2, 10, and 20 mg/kg) by oral gavageonce daily for 3 years. No effect on liver weight (adjustedfor body weight) or liver morphology was observed. The activitiesof catalase, glutathione peroxidase, -glycero phosphate dehydrogenase,benzphetamine N-dernethylase, and ethoxyresorufln O-deethylasewere unaffected by treatment with ciprofibrate. Activity ofglutathione transferase was in creased in the low dosage groupbut unaffected in the mid and high dosage groups. Modest increasesin activities of peroxiso mal ß-oxidation (2.5-fold,maximal), carnitine acetyl transfer ase (1.7-fold, maximal),and carnitine palmitoyl transferase (2- fold, maximal) wereobserved. Cytochemical staining and quan titative image analysisfailed to indicate any effect on peroxisomal number, size, orvolume density. Similarly, there was no increase in lipofuscindeposition. This study provides data on the effects of a potentperoxisome proliferator on pri mate liver following a dosingperiod much greater than that used in previously published studiesand is further evidence that the marmoset is relatively insensitiveto the well-documented effects that ciprofibrate and other peroxisomeproliferators have on rat liver.     

Occupational transmission of HIV in health care workers: A review

Health care workers have a small but real risk of acquiringHIV infection as a result of occupational exposure. In thispaper, we review all reports in the scientific literature from1984 through to December 1993 of confirmed and probable casesof HIV seroconversion after a specific occupational exposure.A total of 64 confirmed cases have been reported, 24 in Europe,36 in the USA and 4 in other countries. Most seroconversionshave resulted from percutaneous exposure (91%) to AIDS patients(62%), usually caused by hollow bore needlestick injuries inflictedduring blood drawing procedures. Almost all seroconversionshave been detected within 6 months of exposure (94%) and haveusually been preceded by an episode of acute illness (73%).Ten seroconversions have occurred in spite of partial or completecourses of zidovudine prophylaxis. An additional 113 probablecases have been reported, 75 in the USA, 35 in Europe and 3in other countries. Aggregating the results of the prospectivestudies carried out, it is calculated that the risk of seroconversionfollowing percutaneous exposure is 0.33% or 3 in 1000 exposures(95% Cl: 0.21–0.52%), while the risk following mucocutaneousexposure is much lower (0.04%, 95% Cl: 0.006–0.31%). Thedocumented failure of zidovudine prophylaxis following occupationalexposure in a number of instances indicate its effect is, atbest, only partial; furthermore, exposure to source patientswho have been receiving the drug may lead to transmission ofzidovudine-resistant strains of HIV. Risk factors for occupationalexposure to HIV and for transmission, given that an exposurehas occurred, are discussed.     

The Effects of {alpha},{beta}-Unsaturated Aldehydes on Hepatic Thiols and Thiol-Containing Enzymes

The effects of series of ,ß-unsaturated aldehydeson hepatic giutathione, cytochrome P450, and NADPH-cytochromec reductase activity were compared with time. Male F-344 ratswere dosed with muconaldehyde (36 µmol/kg), acrolein (89µmol/ kg), crotonaldehyde (450 µmol/kg), or thesaturated aldehyde propionaldehyde (89 µmol/kg) and terminated0.5, 4, or 24 hr later. Acroiein or muconaldehyde reduced glutathioneto 51 and 75% of controls, respectively, at 4 hr; glutathionereturned control values at 24 hr. Only at 24 hr, acrolein, muconaldehyde,or crotonaldehyde decreased cytochrome P450 to 61, 71, and 67%of control values, respectively; ethylmorphine N-demethylationwas decreased to a greater extent, i.e., to 35, 60, and 23%of controls. The reductase activity was unchanged at any timefollowing the treatment with reactive aldehydes which were nothepatotoxic (as shown by glucose 6-phosphatase activity, histologicalchanges, or serum enzymes). Propionaidehyde changed none ofthese activities. Acroiein (44.5 mol/kg) given 4 hr prior tophenobarbital (50 mg/kg) for two consecutive days decreasedthe phenobarbital induction of cytochrome P450 45% of phenobarbitalalone. This treatment also decreased the 2, 2ß, 6ß,l6, and 16ß hydroxylation of testosterone as wellas androstenedione formation showing effects on individual cytochromeP450 isozymes. NADPH-cytochrome c reductase induction was notdecreased by this treatment, thus indicating that in vivo thesechanges are due to a mechanism other than generalized inhibitionof protein synthesis.     

The effect of hypotonicity on the mean platelet volume of patients with thrombo-embolism

Summary When dipotassium EDTA anticoagulated platelet rich plasma was incubated against a range of hypotonic saline concentrations, platelet volume was seen to change in a particular and rcproducible fashion. When platelets taken from patients suffering a thromboembolic episode were tested in the same manner, a different pattern of response was observed the platelets being far less tolerant to osmotic stress. Similar changes occurred in platelets from ante-natal subjects. Platelets from both groups regained their tolerance to hypotonicity following either the thromboembolic incident or parturition respectively.     

WHAT BECOMES OF PEOPLE WITH DEMENTIA REFERRED TO COMMUNITY PSYCHOGERIATRIC TEAMS?

Objective: To monitor key processes and outcomes in joint health and social services community psychogeriatric teams. Design: Six month follow-up of new referrals to 4 teams in Cambridge. Data collected from structured clinical assessment forms at baseline and interviews with keyworkers at follow-up. Data for groups with and without dementia were compared. Setting: Two rural and two urban teams in area with relatively large long stay inpatient facility but low independent sector provision. All were routine service teams, rather than run for research purposes. Main outcome measures: The main outcome measures were survival, institutionalisation, key worker assessments of avoidable admissions, appropriateness of placement, unmet needs, carer stress and global outcome for patient and carers. Results: Rates of referral to urban teams were double rural rates. Around forty percent of the dementia group had a social worker as assessor and keyworker. The dementia group was significantly more dependent and received more informal and formal care. After six months, only 54% of the dementia group were alive and living outside institutional care, compared to 79% in the functionally ill group. Unplanned admissions to hospitals or homes were rarely judged avoidable by keyworkers. Outcomes for carers were judged poor in 15% of both groups, and 13% and 11% of carers respectively were judged to be under severe stress. Unmet needs were more common in the dementia group, and related principally to residential care and carer respite. A number of measures, including evidence of geographical inequity and identification of unmet needs, provided an important contribution to local policy development. Further work is needed on the validity of keyworker assessments of carer stress, given the findings of the carer interview sub-study.