The Most Essential Moral Virtues Enhance Happiness.

Eight moral virtues that have figured prominently in various cultures throughout history will be discussed: altruism, empathy, gratitude, humility, and the "cardinal virtues" of justice, prudence, fortitude, and temperance. The focus will be on how to understand them and what their relationship is to happiness. It will be argued that all eight essential moral virtues enhance happiness in most people most of the time. Their favourable impact on happiness may motivate humans to become better, which includes the decision to subject themselves voluntarily to moral bioenhancement (MBE)-in order to achieve this betterment. Nonetheless, the development of MBE technologies is still in its infancy and moral education remains the primary means for the moral enhancement of humans, as well as for the enhancement of their happiness. This may however change in the relatively near future.

Prevalence and predictors of osteopenia and osteoporosis in adults with Type 1 diabetes.

AIMS: To determine the prevalence and biochemical/hormonal determinants of osteopenia and osteoporosis in adults with Type 1 diabetes. METHODS: One hundred and two patients (52 female, 50 male) with Type 1 diabetes aged 20-71 years underwent cross-sectional assessment of biochemical/hormonal markers of bone metabolism, and bone mineral density (BMD) measurement at forearm, hip and spine using dual energy x-ray absorptiometry. BMD data were available for 102 age- and gender-matched population-based control subjects. RESULTS: After adjusting for age and body mass index (BMI), osteopenia and osteoporosis were more common at the spine in males with Type 1 diabetes than in control subjects (P = 0.030). In Type 1 males, after adjustment for age and BMI, BMD, T- and Z-scores at the hip, femoral neck and spine were lower compared with age-matched control subjects (P < or = 0.048). Female Type 1 patients and control subjects had similar BMDs and T- and Z-scores at all sites. On multiple linear regression analysis, which adjusted for the natural logarithm of the sex hormone binding globulin concentration, smoking status and alcohol consumption, and (for women) menopausal status, each of BMI, serum ionized calcium and serum alkaline phosphatase (negatively) were independently associated with BMD at the hip and femoral neck in Type 1 diabetic subjects. CONCLUSIONS: Adult males with Type 1 diabetes have reduced bone density at the hip, femoral neck and spine when compared with age-matched control subjects. Impaired bone formation may occur in Type 1 diabetes.

Bone mineral density and its determinants in diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: We assessed the effects of type 1 and type 2 diabetes on bone density and metabolism. MATERIALS AND METHODS: We analysed bone mineral density (BMD) measured at the hip, spine and forearm using dual energy X-ray absorptiometry in 34 patients with type 1 and 194 patients with type 2 diabetes. Patients were from the community-based Fremantle Diabetes Study, and findings for them were compared with those from normal age- and sex-matched control subjects from the local community. Biochemical and hormonal markers of bone metabolism were measured in a subset of 70 patients. RESULTS: After adjusting for age and BMI, there was a lower BMD at total hip (p<0.001) and femoral neck (p=0.012) in type 1 men vs control subjects, but type 1 women and matched controls had similar BMD at each site. There was a higher BMD at total hip (p=0.006), femoral neck (p=0.026) and forearm (p<0.001) in type 2 women vs control subjects, but diabetes status was not associated with BMD in type 2 men after adjustment for age and BMI. Serum oestradiol, BMI, C-terminal telopeptide of collagen type 1 and male sex were consistently and independently associated with BMD at forearm, hip and femoral neck and explained 61, 55 and 50% of the total variance in BMD, respectively, at these sites. Spine BMD was independently associated with BMI and ln(oestradiol). CONCLUSIONS/INTERPRETATION: Men with type 1 diabetes may be at increased risk of osteoporosis, while type 2 women appear to be protected even after adjusting for BMI. Low serum oestradiol concentrations may predispose to diabetes-associated osteoporosis regardless of sex.

Influence of pattern of drinking on cardiovascular disease and cardiovascular risk factors--a review.

There is an established inverse relationship between the regular light consumption of alcohol (5-10 g/day) and the incidence of coronary artery disease (CAD). This association has several biologically plausible mechanisms with dose-dependent effects of alcohol to increase HDL cholesterol, lower plasma fibrinogen and inhibit platelet aggregation. However, such a protective effect against atheroma cannot be considered in isolation from known adverse effects on blood pressure and triglycerides or possible detrimental effects of episodic or binge drinking on several other cardiovascular end-points and risk factors. In subjects with pre-existing CAD, an alcoholic binge can increase both silent myocardial ischaemia and angina. During withdrawal following binge drinking, marked fluctuations in blood pressure together with heightened platelet activation and adverse changes in the balance of fibrinolytic factors, may offer an explanation for the reported association between episodic heavy drinking and ischaemic stroke. This has been seen particularly in young males and extends further to an increase in both subarachnoid haemorrhage and intracerebral haemorrhage after binge drinking. Intervention studies in man have shown acute increases in blood pressure in men who drink predominantly at weekends, compared to longer-term pressor effects in regular daily drinkers. We have been unable, however, to reproduce the finding of unfavourable effects of binge drinking on the lipid profile that have been reported in animal studies and man. Binge drinking may also induce cerebrovascular spasm or cause both ventricular and supraventricular arrhythmias, especially atrial fibrillation. Alcohol-induced arrhythmia has been postulated as the basis for alcohol-related sudden coronary death in those subjects with pre-existing CAD. Hence, further exploration of any protective association of alcohol against CAD needs to carefully consider the implications of pattern of drinking for the relationship. The modulating influences of co-timing of drinking with meals, cigarette smoking or illicit drug use also need to be evaluated. Without such vital information, public health advice on alcohol and CAD will be limited in its scope and potentially flawed in its impact.

Effects of coffee on ambulatory blood pressure in older men and women: A randomized controlled trial.

This study assessed the effects of regular coffee drinking on 24-hour ambulatory blood pressure (ABP) in normotensive and hypertensive older men and women. Twenty-two normotensive and 26 hypertensive, nonsmoking men and women, with a mean age of 72.1 years (range, 54 to 89 years), took part in the study. After 2 weeks of a caffeine-free diet, subjects were randomized to continue with the caffeine-free diet and abstain from caffeine-containing drinks or drink instant coffee (5 cups per day, equivalent to 300 mg caffeine per day) in addition to the caffeine-free diet for a further 2 weeks. Change in systolic and diastolic blood pressures (SBP, DBP) determined by 24-hour ambulatory BP monitoring showed significant interactions between coffee drinking and hypertension status. In the hypertensive group, rise in mean 24-hour SBP was greater by 4.8 (SEM, 1.3) mm Hg (P=0.031) and increase in mean 24-hour DBP was higher by 3.0 (1.0) mm Hg (P=0.010) in coffee drinkers than in abstainers. There were no significant differences between abstainers and coffee drinkers in the normotensive group for 24-hour, daytime, or nighttime SBP or DBP. In older men and women with treated or untreated hypertension, ABP increased in coffee drinkers and decreased in abstainers. Restriction of coffee intake may be beneficial in older hypertensive individuals.

The effects of alcohol on coagulation and fibrinolytic factors: a controlled trial.

Light-to-moderate alcohol intake is associated with a reduced incidence of ischaemic cardiovascular events, whilst heavy alcohol intake can predispose individuals to stroke. Alcohol-induced changes in coagulation and fibrinolysis may be relevant and are the subject of this controlled trial of varying alcohol intake in 55 predominantly beer-drinking men. Following 4 weeks stabilization maintaining usual drinking habits, participants were randomized to either continue usual alcohol intake or to restrict alcohol by changing to low alcohol beer for 4 weeks. In a final 4 week period, they crossed over to low or usual alcohol intake, respectively. Comparing combined low and usual alcohol periods, an increase in mean weekly alcohol intake from 92 to 410 ml (mean daily intake from 13 to 58 ml) was associated with a decrease in plasma fibrinogen (by 11%, P < 0.001) and platelet count (3%, P < 0.05), but increases in factor VII (7%, P = 0.001), tissue plasminogen activator (tPA; 16%, P = 0.01) and plasminogen activator inhibitor-1 (PAI-1; 21%, P < 0.001). The ratio, tPA/PAI-1, fell from 0.50 to 0.44 (P = 0.02) confirming the relatively greater increase in PAI-1 with alcohol consumption. Two lipid-associated natural anticoagulants, tissue factor pathway inhibitor and beta 2-glycoprotein-I, did not change. The substantial reduction in plasma fibrinogen with alcohol intake may well contribute to the apparent protection alcohol confers against ischaemic coronary and cerebral events. The increase in factor VII and relatively greater increase in PAI-1 than tPA with alcohol intake may attenuate this benefit and indeed may sufficiently predispose individuals to thrombosis to contribute to the increased incidence of ischaemic stroke seen in heavier drinkers. The balance of anticoagulant and procoagulant and fibrinolytic effects in any individual may vary depending on quantity and type of alcoholic beverage ingested, as well as on genetic and other variables, all of which merit further study.

A controlled trial of the effects of pattern of alcohol intake on serum lipid levels in regular drinkers.

To determine whether the effects of drinking pattern (predominantly weekend versus daily drinking) have differential effects on serum lipids, 55 healthy male drinkers were recruited on the basis of a regular alcohol intake, 210-500 ml absolute alcohol/week (approximately 3-6 standard drinks/day), with more than 60% consumed as beer. Fourteen subjects were categorised as predominantly weekend drinkers, while 41 subjects regularly drank on a daily basis. After maintenance of their drinking pattern during a 4-week familiarisation, subjects were randomised to either consume low alcohol beer (0.9%, v/v) only, or to maintain their usual drinking habit consuming full-strength beer (5%, v/v) for the next 4 weeks. They then switched to full-strength or low alcohol beer, respectively, for a further 4 weeks. Their drinking pattern remained constant during the study. In both weekend and daily drinkers, a reduction in alcohol intake (i.e. from 387 ml/week to 88 ml/week for weekend drinkers and from 418 ml/week to 95 ml/week for daily drinkers, respectively, P < 0.001) resulted in a similar 0.12 mmol/l fall in HDL-C (P < 0.01) with a concomitant significant fall in both apolipoproteins A-I and A-II. In daily drinkers total cholesterol fell by 0.28 mmol/l (P < 0.001) and triglyceride by 0.22 mmol/l (P < 0.01) with a reduction in alcohol intake, but no change in LDL-C was seen. In contrast, weekend drinkers total cholesterol was unchanged while triglyceride decreased by 0.26 mmol/l (P < 0.05) and LDL-C increased by 0.25 mmol/l (P < 0.01). Lp(a) increased with a reduction in alcohol intake in both daily (9.1 U/l, P < 0.05) and weekend drinkers (27.6 U/l, P = 0.07). Previous reports of a more atherogenic lipid profile with episodic versus regular daily drinking were not confirmed in this study and potentially favourable effects of alcohol to increase HDL-C and decrease Lp(a) were shown to be independent of drinking pattern in these moderate to heavy drinkers.

Influence of pattern of alcohol intake on blood pressure in regular drinkers: a controlled trial.

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.

Carbohydrate-deficient transferrin as a marker of change in alcohol intake in men drinking 20 to 60 g of alcohol per day.

We evaluated carbohydrate-deficient transferrin (CDT) and gamma-glutamyltranspeptidase (gamma-GT) as markers of alcohol intake and change in alcohol intake in white Australian men aged 20 to 63 years who regularly drank 20 to 60 g of alcohol/day (2 to 6 standard drinks), either as weekend (n = 14) or daily drinkers (n = 41). After 4 weeks of familiarization on usual alcohol intake, men were provided with low alcohol beer (24 x 375 ml cans, 0.9%, v/v, two-weekly), and, for 4 weeks, consumed as much or as little as they wished with no additional alcohol permitted. In an alternate 4-week period, the same amount of full-strength beer (4.9%, v/v) was provided, whereas subjects continued their usual amount and pattern of alcohol consumption. The order of experimental conditions was randomized. Retrospective 7-day diaries documented weekly alcohol intake during 4 weeks of familiarization and 8 weeks of intervention. Mean alcohol intake was 345 g/week of alcohol (SD 97) during familiarization. During the last 4 weeks of intervention (study weeks 8 to 12), mean alcohol intake either increased by 360 g/week (SD 138) with the switch from low to high alcohol or decreased by 328 g/week (SD 120) with the reverse. During familiarization (study weeks 1 to 4), alcohol intake was significantly related independently (R2 = 0.21) to mean corpuscular volume (p = 0.008) and uric acid (p = 0.003), but not to gamma-GT (p = 0.22) nor CDT (p = 0.94). Change in alcohol intake was predicted independently (R2 = 0.60) by change in CDT (p < 0.0001) and gamma-GT (p = 0.0003), but not by change in uric acid or mean corpuscular volume. A 10% change in CDT gave 70% sensitivity and 80% specificity to detect a change of at least 2 standard drinks/day; respective values were 68% and 0 for 10% change in gamma-GT. Results were not related to drinking pattern, smoking, age, or weight. CDT, particularly when used as a continuous variable, may have a place in monitoring alcohol consumption, even in men whose alcohol intake is in the 20 to 60 g/day range.

Alcohol, hypertension and the cardiovascular system: a critical appraisal.

Cross-sectional and longitudinal population studies have provided a considerable corpus of evidence for an inverse association between light to moderate alcohol intake and both coronary artery disease and stroke. The formulation of balanced public health advice on the basis of such studies, however, needs to take into account the full spectrum of the effects of alcohol on the cardiovascular system, particularly its equally well documented effect to increase level of blood pressure and prevalence of hypertension. In this review, the broader implications of the association of alcohol with hypertension are discussed, principally in the context of the effect of higher levels of alcohol consumption to increase ischaemic and haemorrhagic stroke, left ventricular hypertrophy, congestive cardiomyopathy, cardiac arrhythmia and sudden cardiac death.

Oxidative susceptibility of low-density lipoproteins--influence of regular alcohol use.

In population studies, a low-to-moderate intake of alcohol has been consistently linked to a lower risk of coronary artery disease. The recent suggestion that alcoholic beverages may be conferring this decrease in risk because they contain antioxidant phenolic compounds that reduce the oxidizability of low-density lipoprotein (LDL) has to be reconciled with the possible counteracting influence of a pro-oxidant effect of alcohol. In a controlled crossover study, we have now measured the oxidizability of LDL in 27 regular beer drinkers during consecutive 4-week periods, wherein they consumed a high versus low alcohol beer (4.9 vs. 0.9% alcohol v/v, respectively), with the two beers being similar in phenolic content. This resulted in a decrease in alcohol consumption by approximately 80% (408 +/- 25 ml/week vs. 75 +/- 11 ml/week). During the low alcohol period, there was no change in LDL vitamin E or its cholesterol or protein content. Analysis of LDL oxidation kinetics revealed an increase in oxidizability during the high alcohol phase. This was despite a decrease in arachidonic acid content of LDL and a corresponding increase in palmitic acid during high alcohol intake--a change in fatty acid composition that has the potential to favor a decrease in oxidizability. Our results suggest that alcohol ingestion increases LDL oxidation, despite reducing the polyunsaturated fatty acid composition. The overall effect of alcoholic beverages on LDL oxidation may be a balance between the pro-oxidant and antioxidant activity of its various constituents. The predominant pro-oxidant effect demonstrated in these beer drinkers, although not relevant to any potential decrease in coronary artery disease, may be important in the pathogenesis of alcohol-related disease in other organ systems.

Effect of coffee and tea drinking on postprandial hypotension in older men and women.

1. A postprandial fall in blood pressure (BP) in older men and women increases the risks of falls and impaired cerebral perfusion. Postprandial hypotension has been suggested to be greater in hypertensive subjects, particularly in those on antihypertensive medication. 2. Caffeine, given as tablets or as strong coffee, may attenuate postprandial falls in BP in older subjects, but findings are not consistent. 3. In a randomized controlled intervention in 171 healthy non-smokers over the age of 50 years, we compared the effects of coffee-drinking with abstaining from caffeine in normotensives (NT), untreated hypertensives (UNHT) and subjects on drug treatment for hypertension (TRHT). Tea drinking was a third intervention used only in TRHT. 4. After adjustment for the effects of the initial value on changes in BP, there were no significant differences related to hypertension or to hypertensive agents in the magnitude of postprandial falls in BP. 5. After the intervention, changes in fasting supine and standing systolic BP and heart rate (HR) were not significantly different from controls in NT, UNHT and TRHT, but fasting supine and standing diastolic BP were significantly higher in coffee drinkers in the UNHT group. 6. In normotensive coffee drinkers there was a significant reduction in the postprandial fall in supine systolic BP of 4.1 mmHg (+/- s.e.m. 1.1) and in standing systolic BP of 5.2 +/- 1.6 mmHg. Among untreated hypertensives, abstainers showed a significant attenuation of the postprandial fall in supine, but not standing, systolic BP. Among treated hypertensives who were tea drinkers the postprandial fall decreased for supine systolic BP by 3.8 +/- 1.2 mmHg (P = 0.029) and for standing systolic BP by 5.2 +/- 2.1 mmHg. 7. Both tea and coffee were potentially beneficial in decreasing postprandial falls in systolic BP, but coffee drinking may increase fasting diastolic pressures in untreated hypertensives.

Effects of sphingomyelin and phosphatidylcholine acyl chains on the clearance of triacylglycerol-rich lipoproteins from plasma. Studies with lipid emulsions in rats.

Series of lipid emulsions were prepared as physical models of lymph chylomicrons. The emulsion phospholipid was systematically varied with respect to sphingomyelin, in 0-100% mixtures with egg yolk phosphatidylcholine (EYPC). In other emulsions, the phospholipid was systematically varied with respect to dipalmitoylphosphatidylcholine (DPPC) in 0-100% mixtures with 1-palmitoyl-2-oleoylphosphatidylcholine (POPC). All emulsions contained unlabeled free cholesterol, radiolabeled triolein (TO) and radiolabeled cholesteryl oleate (CO). The emulsions were injected into conscious rats to measure the clearances of emulsion TO and CO and the capture of lipid radioactivity by selected organs. The emulsions containing EYPC or POPC were metabolized similarly to lymph chylomicrons, consistent with rapid lipoprotein lipase-mediated hydrolysis of emulsion TO followed by hepatic uptake of the CO in the triglyceride-depleted emulsion remnants. Emulsions stabilized with either 1-oleoyl-2-stearoyl- or 1-stearoyl-2-oleoylphosphatidylcholine (OSPC or SOPC) were metabolized similarly. Increasing amounts of sphingomyelin in EYPC emulsions progressively slowed the removal of TO and CO labels from plasma. With 50% sphingomyelin clearance was very slow, while emulsion clearance was negligible with 100% sphingomyelin. Emulsions containing 20% of DPPC in POPC were metabolized similarly to 100% POPC, but 40% or more of DPPC progressively slowed the removal from plasma of both TO and CO. With 100% DPPC clearance was characterized by a rapid initial removal of about 30% of the injected material, followed by a second phase when removal was negligible, suggesting lack of hydrolysis of triacylglycerols by lipoprotein lipase. Changes in the apolipoproteins associated with the emulsions probably mediated the observed changes in clearance.

[Ganglioneuroma of the suprarenal glands in gynecologic practice]. / Ganglioneurinoma glandulae suprarenalis u ginekoloskoj praksi.

A 41-year-old patient with enormous tumour in the abdomen, which by its form, size, and position corresponded to a large ovarian tumour, suddenly developed the picture of acute abdomen. Emergency laparotomy revealed a ganglioneurinoma of the right suprarenal gland, 13 X 18 X 20 cm in size, weighing 5.5 kg. The tumour was removed in toto. The postoperative course was normal. So was the finding of the follow-up examination after six months.