Hydroxychloroquine in polymorphic light eruption: a controlled trial with drug and visual sensitivity monitoring

A double-blind controlled trial of oral hydroxychloroquine (HC) treatment in polymorphic light eruption (PLE) was completed in 13 patients on active treatment and 15 on placebo during June, July and August 1982. HC dose was 400 mg daily for the first month and 200 mg daily thereafter. Exposure to ambient solar ultraviolet radiation (UVR) was monitored throughout the trial by polysulphone film lapel badges. Patients scored their symptoms on a visual analogue scale. Drug concentration was monitored in plasma and hair, and oculotoxicity was assessed by visual contrast sensitivity. Moderate clinical improvement occurred, associated with a statistically significant improvement in skin rash (P less than 0.01).     

Increased Plasma Vasopressin and Serum Uric Acid in the Low Renin Type of Essential Hypertension

Abstract The relation between whole blood viscosity and iron status was studied in 11 patients with polycythemia vera (PV) who were treated with venesection without iron supplementation. Six were already iron deficient at the start of the study, five were followed from normal iron status to deficiency. Iron status was investigated with serum ferritin, erythrocyte protoporphyrin, mean cell volume and mean cell hemoglobin. There was no correlation between whole blood viscosity at a fixed erythrocyte volume fraction of 44% and any of these variables. The mean whole blood viscosity during iron deficiency and during normal iron state did not differ. Even after several months of iron deficiency there was no increase in whole blood viscosity. It is concluded that iron deficiency in treated PV does not give increased whole blood viscosity.     

Effects of a national mass-media campaign on physical activity participation

Regular physical activity has an important role in disease preventionand the promotion of positive health. Population-wide campaignsto promote physical activity are a potentially important healthpromotion strategy to increase participation, but little isknown about their effects. A mass-media campaign, supportedby a range of community events, was conducted by the NationalHeart Foundation (NHF) of Australia in 1990 It comprised televisionadvertising, professional education activities and interviews,promotional materials and community events, and was designedto increase knowledge of the preventive role of physical activityand to encourage the sedentary to start walking. Representativenational population surveys were conducted two weeks beforeand four weeks after the campaign in order to determine theimpact of the campaign on the prevalence of physical activity,with particular emphasis on the prevalence of inactivity andwalking. Approximately 75% of participants in the post-campaignsurvey could recall the campaign message. There were no changesin knowledge about the benefits of physical activity, asprecampaign levels were very high. There zs an increase in theproportion of people aged over 50 who reported walking followingthe campaign, and an increase in the number of times per two-weekperiod that walking was reported. Significant effects upon walkingwere also noted in the least educated group. The campaign wasequally effective for both men and women. Such an outcome isencouraging, given concerns about social inequalities in thedistribution of health risk factors.     

A novel mutant variant of the CYP2D6 gene (CYP2D6 17) common in a black African population: association with diminished debrisoquine hydroxylase activity

1The debrisoquine hydroxylase (CYP2D6) is polymorphically distributed. Not only are there differences in the proportions of extensive metabolisers to poor metabolisers in various ethnic groups, but there are also pronounced variations in the metabolic capacity among those classified as extensive metabolisers. 2The mean debrisoquine metabolic ratio of Caucasian extensive metabolisers is lower than that for a number of African populations. In the present study, we have searched for novel CYP2D6 mutations to explain the diminished enzyme activity in African populations. 3Three Zimbabwean Shona subjects with EM phenotypes (metabolic ratios for debrisoquine of 0.4, 1.5 and 10.5 respectively) were selected and the open reading frame of the CYP2D6 gene of each was sequenced. 4The subject with metabolic ratio of 10.5 was found to be homozygous for an allele with a nucleotide exchange in exon 2, ¹¹¹¹C→T causing a ¹⁰⁷Thr→Ile amino acid exchange in a conserved region of the enzyme. In addition, he was homozygous for the ²⁹³⁸C→T and ⁴²⁶⁸G→C mutations causing ²⁹⁶Arg→Ser and ⁴⁸⁶Ser→Thr amino acid substitution found in the CYP2D6*2 allele. 5Seventy-six Zimbabwean Shona subjects were subsequently genotyped for the ¹¹¹¹C→T mutation and for the intron 1 gene conversion present in the CYP2D6*2 gene. The ¹¹¹¹C→T mutation was found at an allele frequency of 34% and was only present in alleles carrying the gene conversion in intron 1 indicative for the CYP2D6*2 gene. 6This allele (CYP2D6*17), containing the ¹¹¹¹C→T, ²⁹³⁸C→T and ⁴²⁶⁸G→C mutations, was found to be strongly associated with lower capacity for debrisoquine hydroxylation. We therefore postulate that the CYP2D6*17 allele might contribute to the molecular basis of the previously established diminished debrisoquine hydroxylase activity in African Bantu populations.     

Heat stable proteinase from Thermomonospora fusca

An extracellular proteinase secreted by the thermophilic bacteria Thermomonospora fusca YX (YX-proteinase) is a serine proteinase as shown by its inactivation by the site specific reagents, phenylmethanesulfonyl fluoride, dansyl fluoride, and carbobenzoxy-l -phenylalanine chloromethyl ketone. This conclusion is further supported by the effect of various proteinase inhibitors on its activity. The activity of the proteinase toward small synthetic ester substrates shows that the enzyme has a primary specificity for the aromatic and hydrophobic amino acids. The amino acid composition and NH₂ -terminal sequence, as well as its size, suggest that the enzyme is related to the chymotrypsin-like microbial proteinase, α-lytic protease from Myxobacter 495 and protease A and B from Streptomyces griseus.     

Prenalterol as Long-term Therapy for Chronic Congestive Heart Failure

Abstract Ten patients with severe chronic congestive heart failure (CHF) due to ischaemic heart disease treated with digitalis and diuretics were randomly allocated to oral treatment with prenalterol (100–200 mg daily in addition to their basal treatment) or to intensified treatment with diuretics in a cross-over trial. A wash-out period of 1–4 weeks was allowed between the two modes of treatment. Most of the patients demonstrated subjective improvement during prenalterol therapy, but this improvement could not be verified objectively by exercise test, echocardiography, chest X-ray or weight measurements. No serious side-effects of either mode of treatment were observed. Heart rate was significantly lower during exercise when the patients were treated with prenalterol than during the control periods or during intensified conventional treatment, indicating that prenalterol acts as a β-adrenergic receptor blocker during exercise in this patient group. The results indicate that prenalterol is a partial β-receptor agonist without superior beneficial effects compared to those of intensified conventional treatment in patients with chronic, severe CHF.     

MULTIPLE RISK FACTOR INTERVENTION IN CARDIOVASCULAR DISEASE

This paper describes multiple risk factor intervention, its rationale and the form it takes, referring to recent intervention trials and the issues arising from their approaches and outcomes. Some questions relevant to intervention are raised and some guesses made as to future directions and opportunities.     

Opinions on treatment of women with habitual abortion based on investigations for blocking antibody and autoantibodies.

Three hundred and thirty-seven women with habitual abortion of unknown etiology were studied for cellular reactivity and blocking antibody in one-way mixed lymphocyte culture. Their sera were investigated for anti-cardiolipin antibodies, antinuclear antibodies, and antibodies against DNA, and the activated partial thromboplastin time (APTT) and complement levels of their plasma were determined. Increased anti-cardiolipin antibody levels were demonstrated in 77 (22%) of the 337 women, all of whom were considered healthy and had no signs of autoimmune disease. Most patients with high anti-cardiolipin antibody levels displayed lowered values of complement factor C4. According to our experiences, the mere occurrence of anti-cardiolipin antibody in women with habitual abortion is no absolute cause for treatment with prednisolone, not even in cases with greatly elevated anti-cardiolipin values. Therapy with prednisolone and acethylsalicylic acid (ASA) during pregnancy should be given to those women who have high levels of anti-cardiolipin antibodies concomitant with high APTT values, low values of complement C4, and strong blocking antibody. Anti-cardiolipin antibody has been investigated during pregnancy in 136 normal pregnant women, 11 of whom (8%) were positive at any sampling occasion, but only one of whom (1%) had high levels. Evidently the development of anti-cardiolipin antibody is no normal feature of pregnancy among Swedish women and thus the high frequency found among healthy Swedish women with habitual abortion remains unexplained. We have introduced an immunization program of leukocyte transfusions in habitual abortion. The development of previously absent blocking antibody seems to be a valuable prognostic sign of possible success for immunization therapy against habitual abortion.