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Isoflavonoids are a class of flavonoids that are derived in the human diet mainly from soybean-based foods. The major dietary isoflavonoids, genistein and daidzein, have estrogen-like activity and are classed as phytoestrogens. Because estrogens can lower serum LDL cholesterol and raise HDL cholesterol, the objective of this study was to determine if isoflavonoids could improve serum lipids in healthy subjects. Forty-six men and 13 postmenopausal women not receiving hormone replacement therapy completed a randomized, double-blind, placebo-controlled trial of two-way parallel design and 8 wk duration. One tablet containing 55 mg of isoflavonoids (predominantly in the form of genistein) or one placebo tablet was taken daily with the evening meal. Subjects maintained their usual diet and physical activity, which were unchanged throughout the intervention. Measurement of isoflavonoids and their metabolites in 24-h urine samples provided an assessment of compliance and of isoflavonoid metabolism. Serum total, LDL, HDL and HDL subclass cholesterol, triglycerides and lipoprotein (a) were assessed at baseline and during the last week of intervention. After adjustment for baseline values, no significant differences in postintervention serum lipid and lipoprotein (a) concentrations between groups were identified. Further adjustment for age, gender and weight change did not alter the results. In addition, changes in urinary isoflavonoids were not significantly correlated with changes in serum lipids and lipoprotein (a). Therefore, this study does not support the hypothesis that isoflavonoid phytoestrogens can improve the serum lipids, at least in subjects with average serum cholesterol concentrations.

OBJECTIVE To evaluate the effects of patterns of drinking (weekend versus daily drinking) on the pressor responses to alcohol in 55 male drinkers using clinic and 24 h ambulatory blood pressure monitoring. DESIGN A randomized, controlled cross-over trial. METHODS Recruitment required a regular alcohol intake of 210-500 ml absolute alcohol/week, with > 60% consumed as beer. Fourteen subjects were categorized as predominantly weekend drinkers, whereas the remaining 41 subjects regularly drank on a daily basis. After 4 weeks of familiarization, all subjects were randomly allocated to drinking low-alcohol beer (0.9% vol:vol) only or to maintain their usual drinking habits with provision of full-strength beer (5% vol:vol) for 4 weeks. They then switched back to their usual drinking habits or low-alcohol beer, respectively, for a further 4 weeks while maintaining their usual drinking pattern. RESULTS Baseline ambulatory systolic blood pressure in weekend but not in daily drinkers was 2.4 mmHg higher on Monday than it was on Thursday (P = 0.02). This Monday-Thursday difference was lost during intervention. When subjects switched from the high-alcohol to the low-alcohol period the falls in ambulatory systolic blood pressure in weekend (3.1 mmHg, P < 0.001) and daily drinkers (2.2 mmHg, P < 0.001) were similar. Most of the fall was evident during week 1 of the low-alcohol period for weekend drinkers but not until week 4 for daily drinkers. CONCLUSION The pressor response to alcohol consumption is similar in magnitude in weekend and daily drinkers, present throughout a 24 h period and has a rapid onset/offset in weekend drinkers but is more sustained in daily drinkers.

This study assessed the effects of short-term circuit weight training (CWT) on glycaemic control in NIDDM. Twenty-seven untrained, sedentary subjects (mean age, 51) with NIDDM participated in an 8-week randomised, controlled study, involving either CWT 3 days/week (n = 15) or no formal exercise (control) (n = 12). All subjects performed regular self-blood glucose monitoring throughout. Fasting serum glucose and insulin were measured following a 12-h fast and during an oral glucose tolerance test (75 g) before and after 8 weeks. Twenty-one subjects completed the study (CWT, n = 11) (Control, n = 10). Strength for all exercises improved significantly after CWT. Pooled time-series analysis, using a random effects model, revealed an overall decrease in self-monitored glucose levels with CWT compared to controls. Significant reductions from baseline values were observed in both the glucose (-213 mmol l-1 per 120 min, P < 0.05) and insulin (-6130 pmol l-1 per 120 min, P < 0.05) area under the curve following CWT relative to controls. After adjustment for body mass changes, the change in self-monitored glucose levels and insulin area under the curve, but not glucose area under the curve, remained significant. Short-term CWT therefore may provide a practical exercise alternative in the lifestyle management of this condition.

1. An antioxidant effect of phenolic substances in red wine to reduce oxidizability of low-density lipoprotein has been proposed as the basis for a relatively lower incidence of coronary disease in populations with high red wine intake. We have now investigated the possible antioxidant effects of various beverages, including red wines, white wines, beers and red grape juices (diluted 1:500), on metal ion-dependent (copper) and -independent (aqueous peroxyl radicals) oxidation of isolated human low-density lipoprotein. We also tested the effects of these beverages on copper-initiated oxidation of lipoproteins in serum. 2. The higher the polyphenolic content of a beverage, the greater was its antioxidative effect measured as change in lag time in the different oxidation systems. Upon stripping the polyphenolics from the drinks, the lag times returned to control levels in isolated low-density lipoprotein; however, the low concentrations of phenolics remaining after stripping had a lesser but still significant effect on oxidation of lipoproteins in serum. The inhibitory effect of these phenolics appeared to be more pronounced for metal ion (copper)-induced oxidation than for those induced by aqueous peroxyl radicals, suggesting that both copper-binding and free radical-trapping activities may be involved. A mixture of the carboxylic acids representative of those present in red wine exhibited no significant effect on lag time of metal iondependent and -independent low-density lipoprotein oxidations. Ethanol, at concentrations of 0.1–0.5%, had no effect on either copper-induced or aqueous peroxyl radical oxidations. 3. Extracts of acid-hydrolysed red wine were separated by thin-layer chromatography and the most active antioxidant fractions identified. GC-MS and HPLC analysis of these fractions resulted in the identification of several cinnamic acid derivatives, such as coumaric acid, caffeic acid and protocatechuic acid. Dose—response studies using the pure compounds indicated that caffeic acid was the most active antioxidant with an IC50 < l μmol/l for copper-initiated low-density lipoprotein oxidation. Caffeic acid (1 μmol/l) significantly inhibited lipid hydroperoxide formation while sparing α-tocopherol consumption. Caffeic acid at the same concentration also inhibits aqueous peroxyl radical-induced oxidation of low-density lipoprotein, sparing α-tocopherol. There was no evidence of caffeic acid preventing the binding of copper to low-density lipoprotein. 4. We conclude that phenolics in both alcoholic and non-alcoholic beverages can give dose-dependent protection against oxidation of low-density lipoprotein. Caffeic acid and protocatechuic acid are two compounds likely to contribute to these effects. These findings may be relevant to the putative cardiovascular-protective effects of high phenolic content alcoholic beverages such as red wine; however, the widespread occurrence of antioxidants such as caffeic acid in fruits and vegetables suggests that these protective principles are not limited to red wine.

Objective To examine whether restriction of caloric intake and exercise of vigorous intensity can independently and additively influence clinic and ambulatory blood pressures in sedentary overweight men. Design Sixty subjects aged 20-50 years were randomly allocated either to continue their normal caloric intake or to restrict it by 4186-6279 kJ/day, with 15% provided by protein, 30% by fat and 55% by carbohydrate, for 16 weeks. Within each of these groups subjects were further randomly allocated either to a control light intensity programme of exercise or to a vigorous intensity programme of exercise for 30min three times a week. The light exercise group performed stationary cycling against no resistance, flexibility exercises and slow walking, The vigorous intensity group cycled on an ergometer at 60-70% of maximum their workload. Results Fifty-one subjects completed the study. Their maximal oxygen uptake was increased by approximately 24% with vigorous exercise but did not change with light exercise. Caloric intake restriction led to a significant loss of body mass of 9.5 kg (95% confidence interval 7.6-11.3), whereas vigorous exercise had no effect Restriction of caloric intake reduced supine clinic systolic and diastolic blood pressures significantly by 5.6 (2.3-8.9) and 2.4 mmHg (0.4-4.2), respectively. Relative to the control light exercise group, exercise of vigorous intensity exercise had no significant effect on clinic blood pressure. In contrast, time series analysis revealed that both caloric intake restriction and vigorous exercise were associated with lower daytime ambulatory systolic blood pressure, the reduction in systolic blood pressure being sustained throughout the 24h period when vigorous exercise and caloric intake restriction were combined. Conclusion Compared with the effects of caloric intake restriction, the effects of a vigorous exercise programme on blood pressure are inconsistent, there being no influence on clinic blood pressure but a reduction in daytime ambulatory blood pressure. However, when combined with caloric intake restriction, regular vigorous exercise exhibits a synergistic effect in reducing ambulatory blood pressure throughout a 24h period.

In addressing the potential for any hazards associated with lowering serum cholesterol, a recent meta-analysis by Law and colleagues (Br Med J 1994;308:373) concluded that that there was no evidence that a low or reduced serum cholesterol concentration increases mortality from any cause other than haemorrhagic stroke. In this review, the evidence for this unexpected association will be addressed, and possible mechanisms discussed. Overall implications of the phenomenon, particularly for the hypertensive patient, will be addressed in the context of the anticipated consequences of lipid-lowering therapy for all stroke, haemorrhagic and non-haemorrhagic, as well as ischaemic heart disease (IHD).

Insulin-dependent diabetics have a greatly increased risk of developing premature coronary artery disease which is not entirely explained by known risk factors. A possible explanation may be enhanced oxidative modification of low density lipoprotein (LDL). The aim of this study was to determine firstly, whether or not LDL from moderately well controlled type 1 diabetics is more readily oxidisable than LDL from healthy non-diabetics and, secondly, to assess whether potential predictors of LDL oxidisability differ between type 1 diabetics and controls. Twenty type 1 diabetic men were carefully matched with healthy non-diabetic men on the basis of age and body mass index and each pair attended the department on the same morning for blood sampling. LDL oxidisability was assessed using both copper in PBS, 15 and 30 mM glucose, and with AAPH. There was no difference between type 1 diabetics and controls in the susceptibility of the LDL to either copper-dependent or non-transition metal-dependent oxidation. Furthermore, there was no difference between the groups for LDL vitamin E content, LDL fatty acid composition in cholesteryl esters, triglycerides or phospholipids, or LDL copper reductive capacity, but LDL glycation was elevated in the IDDM subjects. Given the absence of increased LDL oxidisability in these subjects, the recommendation of vitamin E supplementation in type 1 diabetics should be considered a secondary priority to achieving adequate glucose control.

SUMMARY 1. Changes in membrane fluidity have been proposed to contribute to the pathogenesis of ethanol-induced hypertension possibly through changes in membrane lipid patterns, but reports are inconsistent. 2. In a controlled trial we documented ethanol-induced changes in blood pressure and composition of membrane lipids in ethanol-fed rats. 3. Systolic blood pressure increased significantly in the ethanol-treated rats (9.3 mmHg, s.e.m. 2.9) compared with the control group (- 1.3 mmHg, s.e.m. 2.6). Mean cholesterol content in red cell membranes did not differ significantly between ethanol-fed and control rats. Phospholipids of aorta, red cells and kidney showed a significant decrease in the polyunsaturated to saturated fatty acid ratio, while membrane phospholipids from the heart showed a significant increase in the polyunsaturated to saturated fatty acid ratio with ethanol treatment. 4. In univariate regression blood pressure was significantly negatively related to levels of arachidonic acid in the kidney (P = 0.0013) and to linoleic acid in the aorta (P = 0.0341) and red cells (P = 0.0289). Blood pressure was not significantly related to fatty acids in the heart nor to membrane cholesterol or phospholipids. 5. Differences in fatty acid composition of phospholipids between controls and ethanol-fed rats are consistent with altered membrane fluidity. Altered membrane function is a potential mechanism involved in ethanol-induced hypertension.

1. We have conducted a survey of 75 rural and 75 urban randomly selected general practioners (GPs) in Western Australia to ascertain how closely current practice mirrors published Australian guidelines for the management of hypertension. 2. Fifty-one rural and 49 urban GPs completed the 19 item questionnaire. The two groups were well matched in terms of age and years in general practice. An assessment of the criteria utilized to diagnose hypertension revealed a tendency for much greater scatter in the cut points used to define systolic compared to diastolic hypertension, but no systematic difference between urban and rural GPs. 3. After an initial finding of mild hypertension the follow-up time to the next check-up was significantly longer for rural patients compared to urban patients (72 +/- 13 and 36 +/- 5 days respectively, P < 0.01). Urban GPs reviewed established hypertensive patients more commonly at 1-3 monthly intervals (89%) while rural GPs reviewed more commonly at 3-6 monthly intervals (86%). 4. In terms of target blood pressure (BP) for BP reduction, 67% rural compared to 83% urban GPs aimed for a systolic BP of < 140 mmHg (P = 0.06), while 95% of both groups aimed for diastolic BP < 90 mmHg. 5. The profile of first line antihypertensive agents most commonly used was also similar in both groups with 46% preferring angiotensin converting enzyme inhibitors, 18.5% diuretics, 18.5% beta blockers, 16% calcium entry blockers and 1% prazosin. 6. This study demonstrates a clear preference for the newer anti-hypertensive agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure elevation is frequently associated with elevated cholesterol, triglyceride or low density lipoprotein (LDL-C) or low high density lipoprotein (HDL-C). The relative importance of genetic and environmental factors in these associations is unclear. We examined the relative contribution of genetic and environmental influences to the association between blood pressure and serum lipids in 75 pairs of female twins using path analysis and maximum-likelihood model fitting. Associations between systolic blood pressure and total cholesterol (r = 0.44, P < 0.001), and LDL-C (r = 0.38, P < 0.001), but not HDL-C (r = 0.05, N.S.), remained significant after age and body mass index adjustment. Univariate models suggested genetic effects contributed 60-70% to the variance of total cholesterol, LDL-C, HDL-C and systolic blood pressure. The remaining variance was explained by age and/or unique environmental influences. Using bivariate models, we demonstrated genetic (P = 0.017) and unique environmental covariance (P = 0.011) of cholesterol and systolic blood pressure. Significant genetic covariance (P = 0.038) was observed between LDL-C and systolic blood pressure. The association between blood pressure and total cholesterol in these twins results from shared genetic and similar unique environmental influences. The association between LDL-C and blood pressure is partly due to shared genetic influences. We conclude that both additive genetic and environmental factors unique to the individual are important determinants of the relationships between serum lipids and blood pressure.

Objectives To determine whether vigorous exercise and alcohol restriction have additive and independent effects in reducing blood pressure in sedentary male alcohol drinkers. Also to assess whether 4 weeks of vigorous exercise could offset the fall in high-density lipoprotein cholesterol (HDL-cholesterol) usually observed after alcohol restriction. Design Seventy-five sedentary men were randomly assigned to drink low-alcohol beer or continue their normal drinking habits. Within these two groups subjects were further assigned either to a vigorous exercise programme of three 30-min sessions a week of cycling at 60-70% of maximum workload or to a control light-exercise programme. Results Seventy-two subjects completed the trial. Alcohol consumption fell by 85% in the low-alcohol group. Fitness increased by 10% following vigorous exercise, with a significant improvement in maximum oxygen uptake. After adjustment for weight loss, a significant effect of alcohol restriction in reducing both systolic and diastolic blood pressure was demonstrated. There was no effect of vigorous exercise on blood pressure. Serum total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B were not influenced by alcohol restriction or vigorous exercise. However, alcohol restriction significantly reduced triglyceride, HDL-cholesterol, its subfractions HDL2-cholesterol and HDL3-cholesterol, and its major apolipoproteins apo A-I and apo A-II. These reductions were unaffected by moderate exercise. Conclusions This study provides further evidence that alcohol restriction results in reductions in blood pressure in men who are regular alcohol drinkers. However, a simultaneous increase in fitness did not lead to lower blood pressures than those achieved with alcohol restriction alone, and was unable to offset alcohol-related falls in HDL-cholesterol, its subfractions and its major apolipoproteins.

In a group of 343 working men, only 34 of whom regularly drank more than 60 ml of ethanol per day, logistic regression was used to determine the combination of biomarkers which best discriminated between those who regularly drank less than 30 ml or 30 ml or more of ethanol daily. The index consisted of apolipoprotein A-II, uric acid, gamma-glutamyl transpeptidase and mean corpuscular volume. Even with the relatively low level of alcohol intake reported in these subjects (assessed using a 7-day retrospective alcohol diary), the groups with higher or lower intake of alcohol were separated with a sensitivity of 68%, a specificity of 74% and a positive predictive value of 71%. Systolic blood pressure, adjusted for age and body mass index, was also linearly related to alcohol intake, and when included in the biomarker index improved the proportion correctly classified from 71% to 75%. Using the biomarkers only, 94% of subjects regularly drinking at least 80 ml of ethanol equivalent per day and 100% of the non-drinkers were correctly classified.

We have examined the independent and combined effects on blood pressure and blood lipids of alcohol restriction and weight loss in overweight male drinkers with a view to assessing overall effects on cardiovascular risk of two widely promoted nonpharmacological approaches for hypertension. Eighty-six men with a mean age of 44.3 years, a mean regular alcohol intake of 440 ml/wk (five or six standard drinks per day), a mean blood pressure of 137.4 mm Hg systolic and 84.8 mm Hg diastolic, and a mean body mass of 92.5 kg entered a controlled two-way factorial study. The subjects were randomly assigned to four groups for an 18-week intervention in which members of two groups drank only low-alcohol beer, thereby reducing their alcohol intake by 374 ml/wk, while those of the other two groups continued their normal alcohol intake. Within the low and normal alcohol intake groups subjects either continued their usual diet or reduced their caloric intake by 4,200-6,300 kJ/day (1,000-1,500 kcal/day) (with protein, fat, and carbohydrate provided as 15%, 30%, and 55% of total calories, respectively). Calorie reduction and alcohol restriction caused weight losses of 7.5 (p less than 0.001) and 2.1 (p less than 0.01) kg, respectively. Calorie reduction and alcohol restriction were associated with decreases in systolic blood pressure of 5.4 (p less than 0.001) and 4.8 (p less than 0.01) mm Hg, respectively, and in diastolic blood pressure of 4.2 (p less than 0.001) and 3.3 (p less than 0.01) mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

In a study of 843 independent-living men and women aged between 60 and 87 in Perth, Western Australia, stepwise multiple regression, after correction for initial levels of systolic blood pressure, showed that postural fall in systolic blood pressure was positively related to alcohol intake of more than 20 ml/day, the use of sleeping tablets and higher levels of anxiety on the Spielberger state-trait scale, and negatively related to body mass index. Postural fall in blood pressure was not significantly related to treatment for hypertension, age, sex, patterns of usual physical activity, tea or coffee drinking, or the diagnosis of diabetes mellitus. This analysis is the first to examine the relationship between lifestyle factors and the magnitude of the fall in systolic blood pressure on standing after adjustment for the association between the change in a variable and its initial level. Our analysis suggests the need for further study of the possible role of lifestyle factors such as the use of sleeping tablets and alcohol in postural hypotension in the elderly.

1. We used path analysis and maximum-likelihood model fitting to evaluate the relative contributions of genetic and environmental factors to the relationships observed between level of blood pressure and both total plasma calcium concentration and platelet cytosolic free calcium concentration in 109 twin pairs. 2. Total plasma calcium concentration was positively associated with systolic (r = 0.26, P < 0.001) but not diastolic blood pressure, a relationship which remained significant after adjustment for albumin, age and body mass index. A relationship between platelet cytosolic free calcium concentration and both systolic and diastolic blood pressure (r=0.17 and r=0.13, respectively, P ≤ 0.05) was no longer significant after adjustment for age and body mass index. 3. Additive genetic influences, unique environmental effects and age contributed to 60%, 30% and 10% of the variance in systolic blood pressure, respectively. Additive genetic effects explained 78% of the variance in plasma total calcium concentration and at least 48% of the variance in platelet cytosolic free calcium concentration in females and 37% in males. 4. Bivariate factor models provided evidence of genetic, but not environmental, co-variation of total plasma calcium concentration and systolic blood pressure, suggesting that a common genetic factor (or factors) contributes to their univariate relationship. In contrast, there was evidence of environmental, but not genetic, covariation of platelet cytosolic free calcium concentration and systolic blood pressure, suggesting that some of the individual experiences specific to each twin may be causing these two traits to vary together. 5. The possible confounding effects of adiposity and environmental factors should be considered in future studies investigating the role of intracellular calcium levels in the pathogenesis of hypertension.

SUMMARY 1. From an earlier cross-sectional survey of 343 public servants, 15 pairs of non-smoking teetotallers and heavy drinkers (alcohol intake more than 350 mL/week) were matched for age and adiposity and utilized for a case-control study of the effects of alcohol on 11β-hydroxysteroid dehydrogenase (11β-OHSD) activity and blood pressure. 2. Two successive 24 h urine collections were analysed by radio-immunoassay (RIA) for cortisol excretion, and for the cortisol and cortisone metabolites, tetrahydrocortisol (THC), allo-tetrahydrocortisol (allo-THC) and tetrahydrocortisone (THE), by capillary column gas chromatography. 3. Heavy drinkers had higher systolic and diastolic blood pressure (BP) than teetotallers (132.6 ± 2.5 vs 123.2 ± 1.3 and 78.7 ± 1.6 vs 71.7 ± 1.4, respectively; unpaired t-test, P

SUMMARY 1. To investigate the effect of an exercise training programme on antihypertensive drug requirements, 19 sedentary subjects (14 men and five women) with mild essential hypertension (systolic blood pressure greater than 140 mmHg but less than 180 mmHg), aged 29–55 years, were randomly assigned to 16 weeks of moderate intensity exercise or light intensity exercise (control), and titrated on antihypertensive drug therapy (captopril and hydrochlorothiazide) until resting systolic blood pressure (sitting) of less than 140 mmHg was achieved. 2. The moderate exercise group (n= 11) followed a graded walk-jog programme to >60% age-predicted maximum heart rate (HRmax), attending 45 min sessions, three times each week. The light exercise group (n= 8) followed a programme of flexibility (stretching exercises) and walking to

To determine the early effect of potassium loading on blood pressure regulatory mechanisms, the effect of 4 days' supplementation with 80 mmol/day KCl on blood pressure and vasodilator hormone release was examined using a double-blind crossover design in normotensive women with a baseline potassium excretion of 51.8 +/- 2.7 mmol/day. Systolic blood pressure fell 1.7 +/- 0.6 mm Hg, (P less than .01) in association with a mean increase in sodium excretion of 14.7 +/- 4.5 mmol/day and an increase in urine volume of 122.6 +/- 57.0 mL/day. There was a small but significant fall in plasma atrial natriuretic peptide (ANP) over the 4 days of potassium supplementation, while significant increases were seen in the levels of plasma potassium (P less than .01) and aldosterone (P less than .01). After 4 days of KCl, urinary 6-keto-PGF1 alpha was significantly elevated and correlated positively with urinary sodium excretion. Plasma renin activity was unchanged. The results suggest that increased vasodilator prostanoid synthesis and a mild natriuresis may contribute to the transient fall in systolic blood pressure. The increase in aldosterone and reduction in ANP probably represent homeostatic responses to this natriuresis, and could account for the failure of potassium supplementation to induce a long-term reduction in blood pressure in other studies in normotensive subjects.

The dyslipidemia of type 2 diabetes includes the accumulation of small dense LDL particles in plasma that have an increased propensity to glycation and oxidation and may contribute to the endothelial dysfunction in type 2 diabetic patients. We recently reported that both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the two major dietary long-chain n-3 fatty acids, significantly reduced triglycerides and increased HDL2 cholesterol without changing total, LDL, or HDL cholesterol in a group of type 2 diabetic subjects (1). We now report additional data …

Epidemiological studies have found evidence of lower blood pressure in smokers and predict an increase in blood pressure after stopping smoking. We have therefore monitored blood pressure change in 33 smokers following entry into a 6-week smoking cessation programme and compared the results to 33 matched controls who continued their normal smoking habits over the same period. Fourteen subjects were successful in quitting smoking for the entire 6 weeks, 13 were unsuccessful and 6 withdrew before completion of the programme. No significant increase in supine or erect systolic or diastolic blood pressure was observed following reduction in or cessation of smoking habit. Complete cessation of smoking was, however, associated with an increase in weight and anxiety levels and a decrease in alcohol consumption. We conclude that although stopping smoking affects several factors which may potentially influence blood pressure, this does not result in any significant change in blood pressure over a 6-week period. Concern that advice to patients to cease smoking may lead to a prompt increase in blood pressure appears unnecessary.

Serum levels of cholesterol, triglyceride, cholesterol in low density lipoprotein (LDL) and in high density lipoprotein (HDL) and its major subfractions, and of apolipoproteins A-I, A-II and B were measured in 48 healthy men at the end of two 6-week periods in which they consumed normal alcohol (5.0%, v/v) or low alcohol (0.9%, v/v) beer, respectively. Other dietary and behavioural variables were kept constant. Mean levels of triglyceride, HDL cholesterol, HDL2- and HDL3 cholesterol, and apolipoproteins A-I and A-II were higher at the end of the normal compared with the low alcohol periods, and levels of LDL cholesterol were lower. Body weight was greater at the end of the normal alcohol period than at the end of the period of low alcohol but multiple regression analysis suggested that the changes in lipoprotein-lipid and apolipoprotein levels were due primarily to the change in alcohol consumption rather than concomitant changes in body weight. This study confirms an effect of alcohol on both major subfractions of HDL and on its major apolipoproteins.

SUMMARY 1. Forty-six healthy normotensive male drinkers participated in a randomized, controlled, crossover trial to study the effects of varying alcohol intake on blood pressure. 2. Alcohol consumption (calculated from weekly diaries) was reduced from 336.3 (s.e.m. = 20.2) to 64.5 (s.e.m. = 5.6) ml ethanol/week by drinking low alcohol content beer alone. 3. Systolic blood pressure fell significantly during reduction of alcohol intake and rose again when normal drinking habits were resumed, the mean difference during the last 2 weeks of normal or low alcohol intake being 3.8 mmHg. 4. This effect of alcohol on blood pressure was independent of a small but significant decrease in weight following reduction of alcohol intake. 5. The change in blood pressure correlated with change in alcohol consumption (r= 0.53, P

44 men with treated essential hypertension who were moderate to heavy drinkers took part in a randomised, controlled, crossover trial of the effects of alcohol intake on blood pressure. Usual antihypertensive treatment was maintained throughout 6 weeks of normal drinking and 6 weeks of drinking only a low-alcohol beer. Self-reported changes in alcohol consumption (mean [SEM] from 452 [30] ml ethanol/week during normal drinking to 64 [8] ml/week while drinking the low-alcohol beer) were confirmed by biochemical measurements. Mean systolic and diastolic blood pressures were significantly lower during the last 2 weeks of the low-alcohol period than during the normal-alcohol period, the mean difference in the supine readings being 5.0 (1.4) and 3.0 (0.9) mm Hg, respectively. Regression analysis suggested that reduction in alcohol intake contributed to the fall in both systolic and diastolic blood pressures independently of changes in weight. Thus, curtailing alcohol intake may lead to improved blood-pressure control and may reduce the need for antihypertensive drugs.

The haemodynamic and neuroendocrine consequences of stopping smoking for a 6 week period were studied in thirty-three smokers and their matched controls. Complete smoking cessation was associated with a significant fall in adrenaline and cortisol levels, consistent with the withdrawal of a nicotine stimulus to adrenomedullary and cortical activity. Supine systolic and diastolic blood pressure did not change significantly. However, the response to a cold pressor stimulus was altered with a delay in return of systolic blood pressure to basal values. This study has been unable to confirm findings from epidemiological studies of lower blood pressure in smokers. However, the possibility is raised that this phenomenon may be due to modification by smoking of the normal physiological response to stressful stimuli.

Forty-four males with treated essential hypertension and a moderate-to-heavy alcohol intake participated in a randomized controlled crossover trial of the effects of varying alcohol intake on blood pressure control. Usual antihypertensive therapy was maintained unchanged throughout. Self-reported alcohol consumption fell from 452 ml ethanol/week (s.e.m. = 29) during normal drinking habits to 64 ml/week (s.e.m. = 8) while drinking low alcohol content beer. Mean systolic and diastolic blood pressures were significantly lower during the last 2 weeks of reduced alcohol (supine 5.0 mmHg, s.e.m. = 1.4, and 3.0 mmHg, s.e.m. = 0.9, respectively; erect 5.9 mmHg, s.e.m. = 1.6, and 2.9 mmHg, s.e.m. = 1.0, respectively). Body weight was also lower (0.94 kg, s.e.m. = 0.25) at the conclusion of the low alcohol intake period. Regression analysis suggested that reduction in alcohol intake contributed independently to the fall in both systolic and diastolic blood pressure, while weight change contributed independently to the fall in systolic blood pressure alone. It was concluded that curtailing moderate to heavy alcohol intake leads to improved blood pressure control in treated essential hypertensive males.

Sulphate conjugation represents an efficient mechanism for inactivating catecholamines (CA) with more than 80% of total noradrenaline (NA) and adrenaline (A) and nearly 100% of dopamine (DA), circulating as conjugates. Sulphate conjugation responds rapidly to changes in sympathetic activity and may buffer the haemodynamic and metabolic consequences of wide fluctuations in CA release in phaeochromocytoma. This hypothesis was tested in seven patients with phaeochromocytoma by consecutive measurements of plasma free and conjugated NA, under resting conditions, before operation and at least 4 weeks after tumour removal. Free and total (free plus sulphates) NA were markedly elevated before (4.3, s.e.m. = 1.8 and 13.7, s.e.m. = 4.4 ng/ml, respectively) compared with 1-4 months after surgery (0.48, s.e.m. = 0.13 and 1.8, s.e.m. = 0.53 ng/ml). A and DA were similarly elevated before surgery; after surgery, A was undetectable in three patients and DA was undetectable in all patients. Before surgery consecutive measurements of total NA, 5 min apart, were markedly different (18.8, s.e.m. = 4.8 and 12, s.e.m. = 3.1 ng/ml, respectively), whereas only small differences in free NA levels were present (4.0, s.e.m. = 1.5 and 4.4, s.e.m. = 1.8 ng/ml). In three patients, fluctuations in total NA concentration greater than 12 ng/ml were associated with either no change (one patient) or changes of 0.6 and 2.8 ng/ml in levels of free NA, respectively. Mean blood pressure varied less than 8 mmHg in these patients. These findings indicate that sulphate conjugation is a dynamic process which may limit wide fluctuations in free CA concentration during episodic secretory activity in phaeochromocytoma.

Determinants of change in blood pressure between two examinations separated by a 6-year period were investigated in 340 working men aged 20-45 at first examination and not on antihypertensive medication at either examination. A London School of Hygiene sphygmomanometer was used for all measurements of blood pressure. Relationships between change in blood pressure (residuals of follow-up blood pressure regressed on baseline blood pressure) and changes in weight, physical activity, cigarette smoking, diet, alcohol intake and a range of psychological characteristics were examined using multiple regression. Systolic and diastolic changes in blood pressure were both positively related to baseline age and weight. Regression equations indicated independent effects of change in weight, with similar increases of 0.5 (s.e. 0.1) mmHg in systolic and diastolic blood pressure for each kg of weight gain. Decreased coffee consumption and increased participation in sports were negatively associated with systolic changes in blood pressure. Men who had stopped smoking cigarettes were observed to have higher than average increases in both systolic and diastolic blood pressure, although these relationships were not independent of other variables. The difference in ambient temperature between baseline and follow-up measurement days was an important determinant of change. Changes in mean systolic and mean diastolic blood pressure in 76 manual workers (+10.1/+6.4 mmHg) compared unfavourably with changes in professional men (-2.8/+2.7 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

The ingestion of cold fluids results in a rise in plasma norepinephrine (NE) and a fall in plasma epinephrine (E). To assess the relative roles of fluid volume and temperature in mediating this dissociated sympathetic response to drinking, NE and E levels were measured on 3 separate occasions in 10 men before and after ingestion of either 750 ml distilled water at 4 C, 750 ml at 25 C, or 150 ml at 4 C. An increase in plasma NE occurred after drinking 750 ml water at both 4 C and 25 C. Levels rose during ingestion of fluid and fell again when drinking was completed, consistent with a sympathetic response to deglutition. There was no change after 150 ml at 4 C. In contrast, plasma E fell after the men drank 750 ml water at 4 C, but it did not change after they drank 750 ml water at 25 C or 150 ml at 4 C. The fall was maximal 10 min after drinking was completed and levels remained depressed for a further 30 min. These findings suggest that the fall in E is temperature dependent and is a response to the presence of cold fluid in the stomach rather than to deglutition. We conclude that the dissociation of the plasma NE and E response after drinking cold fluids is therefore a result of independent and contrasting influences of, respectively, the volume and temperature of the fluid ingested.

Alcohol stimulation of the renin-angiotensin axis has been proposed as an explanation for the higher blood pressure in drinkers. This study examines the acute effects of moderate alcohol intake on PRA in relation to change in fluid and electrolyte balance, sympatho-adrenal activity, blood pressure, and heart rate in 20 normal men, aged 20-24 yr. They consumed either 750 ml nonalcoholic beer as a control or the same beverage with 1 ml/kg alcohol added, which increased the plasma alcohol concentration to 16.7 +/- 1.0 (+/- SE) mM within 70 min. PRA increased more than 2-fold 90 min after the ingestion of alcohol. This was accompanied by a decrease in diastolic blood pressure and a fall in plasma potassium, both possible stimuli to the rise in PRA. A late increase in plasma sodium, also occurring 90 min after alcohol ingestion, was attributed to plasma volume contraction after an alcohol-induced diuresis. This may have been an additional factor in stimulating renin release. Norepinephrine levels increased during both alcohol and control studies. In contrast, plasma epinephrine decreased significantly during the control study, but did not change after alcohol ingestion. Hence, alcohol stimulation of sympathetic nervous activity is unlikely to have mediated the renin release. We conclude that the acute increase in PRA associated with moderate alcohol consumption is predominantly a secondary response to changes in fluid and electrolyte balance and blood pressure. Although a direct action of alcohol on renin release was not excluded, the possibility that repeated activation of the renin-angiotensin system mediates the pressor effect of regular moderate alcohol consumption is, therefore, diminished.

SUMMARY 1. In a population-based study of 343 men from two public utilities, 260 subjects reported drinking alcohol at least once a week. In these subjects a comparison was made of the relative effects on blood pressure of either their usual alcohol intake (assessed from a 7-day retrospective diary) or recent alcohol intake (alcohol consumed at the last drinking session in the 24 h prior to blood pressure measurement). 2. Both usual and recent alcohol intake showed similar correlations with level of blood pressure (BP). After adjustment of BP for the potential confounding influences of body mass index, age and smoking status, systolic and diastolic BP remained highest in those subjects with the highest reported levels of both usual and recent alcohol intake. 3. In regression analyses comprising only those subjects who reported drinking in the 24 h before BP measurement, a 3–4 fold greater effect of usual rather than recent intake on both systolic and diastolic BP was predicted from the b coefficients. Regression analysis also demonstrated that the relationship between usual alcohol intake and BP was independent of recent intake, while the relationship between recent intake and BP was no longer significant when usual alcohol intake was entered into the regression equation. 4. These observations suggest that consistent regular drinking is a more important determinant of the alcohol/BP relationship than intake in the previous 24 h.

A direct pressor effect of alcohol is proposed as the basis for the association between regular alcohol consumption and an increase in blood pressure found in population studies. To examine this further, a randomized controlled crossover trial of the effects of varying alcohol intake on blood pressure in 46 healthy male drinkers was conducted. From an average of 336 ml of ethanol per week, alcohol consumption was reduced by 80% for 6 weeks by drinking a low alcohol content beer alone. This reduction was associated with a significant reduction in systolic and diastolic blood pressure (p less than 0.001 and p less than 0.05 respectively). The mean difference in supine systolic blood pressure during the last 2 weeks of normal or low alcohol intake was 3.8 mm Hg, which correlated significantly with change in alcohol consumption (r = 0.53, p less than 0.001). Reduction of alcohol intake also caused a significant decrease in weight (p less than 0.001). After adjustment for weight change, an independent effect of alcohol on systolic but not diastolic blood pressure was still evident, with a 3.1 mm Hg fall predicted for a decrease in consumption from 350 ml of ethanol equivalent per week to 70 ml per week (p less than 0.01). Systolic blood pressure rose again when normal drinking habits were resumed. These results provide clear evidence for a direct and reversible pressor effect of regular moderate alcohol consumption in normotensive men and suggest that alcohol may play a major role in the genesis of early stages of blood pressure elevation.

Reiter's syndrome following antibiotic- associated colitis. I. B. Puddey, Aust. N.Z. J. Med., 1982, 12, pp. 292-293. The first case report of Reiter's syndrome following Clostridiu m d ifficile induced antibiotic-associated colitis is presented, together with a discussion of previous case reports of arthritis complicating antibiotic- associated colitis. Dysentery followed by the triad of arthritis, con- junctivitis and urethritis was first reported by Stoll in 1776.' However, this syndrome did not become firmly established until in 1916, during the first world war, Hans Reiter2 on the Balkan front described "Spirochaetosis arthritica" while Fiessenger and Leroy3 on the Somme front simultaneously described "conjunctival- urethral-synovial syndrome", each following dysenteric episodes. Two classic studies of post- dysenteric Reiter's syndrome have since been made. The first was by Paronen in 19484, who reported 344 cases of Reiter's syndrome follow- ing an epidemic of Shigellu Jexneri enteritis in Finland during the second world war. The epidemic affected over 150,000 people giving an incidence of Reiter's syndrome of 0.2x. The second study was by Noer in 19665 following an outbreak of shigellosis on an American naval vessel with a crew of 1276 in 1962. There were 602 cases of proven Slzigellu Jexneri infection and nine cases of Reiter's syndrome followed the infection.

1. Attenuation of the effectiveness of antihypertensive therapy by non-steroidal antiinflammatory (NSAI) drugs has been attributed to inhibition of systemic or renal vasodilator prostaglandin synthesis, or a combination of both. 2. Indomethacin is a NSAI drug with both renal and extrarenal cyclo-oxygenase inhibition properties. Sulindac is a relatively selective cyclooxygenase inhibitor said not to affect urinary prostaglandin excretion. 3. This study examines the relative effect on blood pressure of 4 weeks' treatment, with indomethacin 25 mg three times daily and sulindac 200 mg twice daily, in a randomized placebo controlled trial in 26 hypertensive subjects. 4. In nine patients treated with indomethacin, supine blood pressure rose 11 mmHg systolic and 4 mmHg diastolic by the end of the first week, whereas nine subjects treated with sulindac showed a fall in blood pressure similar to the trend seen in placebo-treated subjects. 5. Indomethacin treatment inhibited renal cyclo-oxygenase with a 78% reduction in urinary prostaglandin E2 excretion and 89% suppression of plasma renin activity. Neither measurement was affected by sulindac. Extrarenal cyclo-oxygenase activity was inhibited by both indomethacin and sulindac with serum thromboxane B2 decreasing by 96% and 69% respectively. 6. The results suggest that the pressor effect of NSAI drugs is predominantly related to renal cyclo-oxygenase inhibition. The lack of effect of sulindac on blood pressure may make it a safer therapeutic option if NSAI drug therapy is necessary in the hypertensive patient.