Seasonal variation of serum 25-hydroxyvitamin D levels in adult patients with inflammatory bowel disease.

UNLABELLED: Patients with inflammatory bowel disease (IBD) are at risk of osteoporosis. Vitamin D (vitD) deficiency is known as a risk factor of osteoporosis. We observed low vitD blood levels in adult IBD patients both at the end of summer and winter. Furthermore, effects of oral vitD supplementation in (generally low) daily dosages were poor. INTRODUCTION: Patients with IBD are at risk of osteoporosis. This study evaluates seasonal vitD status, determinants of vitD deficiency and effects of vitD supplementation in adult IBD patients. METHODS: Patients were screened for vitD deficiency at the end of summer and winter using serum 25OHD(3) (cut-off point, <50 nmol/L) combined with routine laboratory tests. A standardized questionnaire was used for demographic/lifestyle data i.e. IBD activity, health behaviour and vitD intake through diet and ultraviolet light. RESULTS: Late-summer, 39% of the included 316 patients were vitD deficient. Late-winter, 57% of the follow-up patients (n=281) were deficient. Independent protective determinants of vitD deficiency were oral vitD supplementation (summer/winter: odds ratio [OR], 0.52 [95% confidence interval [CI], 0.29-0.94]/OR, 0.44 [95% CI, 0.26-0.75]), recent sun holiday (summer: OR, 0.42 [95% CI, 0.24-0.74]) and regular solarium visits (summer/winter: OR, 0.28 [95% CI, 0.13-0.63]/OR, 0.17 [0.06-0.50]). IBD activity (p=0.031), red blood cell distribution width (RDW; p=0.04) and erythrocyte sedimentation rate (p=0.03) were associated with low vitD levels using univariate analyses of the extreme 25OHD quartiles. In a subgroup with vitD supplementation, still 30% (late-summer) and 44% (late-winter) were vitD deficient. CONCLUSION: VitD deficiency is common in IBD patients, but prevalence might be comparable with the general population. Ultraviolet light is essential for adequate vitD levels. Effects of oral vitD supplementation in (generally low) daily dosages are poor. Determinants for low vitD levels were IBD activity and elevated inflammatory markers, suggesting that increased risk of osteoporosis in IBD might be more related to the inflammation than to vitD deficiency.

Cardiovascular risk is more related to drinking pattern than to the type of alcoholic drinks.

Many observational studies have shown an association between moderate alcohol consumption and a lower risk for cardiovascular morbidity and mortality. Some of these studies, whether or not inspired by the French paradox, suggest a more favourable effect of wine than of other alcoholic drinks. Certain polyphenols including the flavonoids, more abundant in red than in white wine, are held responsible for this 'bonus' effect. However, this conclusion seems premature, since no significant bioactive effect of wine polyphenols has been shown in humans so far. Furthermore, wine drinking proves to be associated with a healthier lifestyle profile than consumption of beer and liquor, and this may have a substantial influence on the outcome of studies. In contrast to moderate drinking, incidental heavy or binge drinking is associated with an increased cardiovascular risk by influences both on the electrical conduction system of the heart and the process of atherothrombosis. Although only prospective randomised intervention trials including a sufficient number of people will give definite answers, the chances are small that they will ever be performed given the ethical and practical objections of such studies. Available data so far justify the conclusion with regard to cardiovascular risk that the pattern of drinking is of more importance than the content of the bottle.

Binge drinking causes endothelial dysfunction, which is not prevented by wine polyphenols: a small trial in healthy volunteers.

BACKGROUND: Binge drinking (the consumption of large quantities (>5 units) of alcohol in a short period) is associated with increased cardiovascular mortality. Wine polyphenols are considered to be protective against cardiovascular diseases. We conducted an experimental study to evaluate the acute effects of alcohol consumption on flow-mediated vasodilation and general cardiovascular parameters, using beverages with high polyphenolic content (HPC) and low polyphenolic content (LPC). METHODS: Two groups of ten volunteers were asked to drink two different kinds of beverages. in 45 minutes, three units of red wine or an alcoholic beverage with a low polyphenolic count were consumed. Then 45 minutes were allowed for complete uptake of the alcohol or polyphenolic compounds. Next, all volunteers underwent blood pressure readings, ECG and flow-mediated vasodilation. Blood samples were taken at the same time for routine chemistry, inflammation parameters and lipids. Then the entire cycle was repeated once (in total six units of alcohol in 180 minutes). RESULTS: No differences were found between the two drinks. Alcohol itself dose-dependently increased forearm blood flow by vasodilation of both arterioles and distribution arteries. However, flow-mediated vasodilation (FMD) for the LPC group (n=10) decreased from 7.31 +/- 4.78 (% +/- sd) to 2.82 +/- 2.9 after three drinks and 1.21 +/- 3.25 after six drinks. The FMD values for the HPC group (n=10) decreased from 8.61 +/- 1.78 to 1.78 +/- 3.71 and 1.19 +/- 2.6. There were no significant changes between the LPC and the LPC group at the three time points. CONCLUSION: Although ethanol produces vasodilation at the level of the distribution artery as well as at an arteriolar level, it causes a decrease in flow-mediated vasodilation. This endothelial dysfunction is not corrected by the polyphenols present in wine.

[The practice guideline 'Problematic alcohol consumption' (second revision) from the Dutch College of General Practitioners; a response from the perspective of internal medicine]. / De standaard 'Problematisch alcoholgebruik' (tweede herziening) van het Nederlands Huisartsen Genootschap; reactie vanuit de interne geneeskunde.

The prevalence of problem drinking in the Dutch population, affecting about 750,000 persons, is much higher than that of abuse or addiction and contributes substantially to healthcare workload and costs. However, recognition, not only in primary care but also in the hospital environment, can be difficult. The symptoms are often non-specific and are not always immediately related to the use of alcohol. Even in cases of overt abuse, like in injuries and trauma, routine drinking histories are recorded poorly and identification and signalling are inadequate. It is estimated that up to 16% of all emergency room patients have consumed alcohol within six hours before their visit. Since a patient will benefit not only from the treatment of his symptoms but also from the uncovering of the underlying problem, more emphasis should be laid on the early identification of problem drinking. Especially in the early phase of problem drinking, interventions, in most cases by primary-care physicians or nurse practitioners, may be successful. Since the revised version of the practice guideline 'Problematic alcohol consumption' from the Dutch College of General Practitioners contains clear and practical advice on the early recognition and management of problem drinking, its use is recommended not only to primary-care physicians but also to hospital-specialist staff.

Substance use among emergency room patients: Is self-report preferable to biochemical markers?

AIM OF STUDY: To explore the validity of self-reported substance use among emergency room populations and the processes of sample selection bias, to establish their influence on the prevalence rates found. METHODS: Self-reported alcohol and illicit drug use of patients in the emergency room is compared with results from an alcohol breath analyser and urine toxicology. RESULTS: Variations in reported substance use occur when comparing self-report measures with alcohol breath analyser results and urine toxicology. Self-reported alcohol use was found among 7.5% of the patients compared with 4.7% based on alcohol breath analysers. Illicit drug use was reported by 9.0% of the patients whereas urine toxicology resulted in 30% patients positive for illicit drug use. Patients that voluntarily participate in the study differ from those that do not participate. Patients who refuse an alcohol breath analyser report slightly more alcohol use prior to the injury (difference not significant), and patients who provide a urine sample report more illicit drug use prior to the injury compared to those that refuse. DISCUSSION: Differences in prevalence rates can be explained partly by the measurements used and partly by sample selection bias. Self-reported alcohol use and self-reported illicit drug use are preferable to the "gold standard" when used among emergency room patients, because both measures provide more accurate information on the actual use. Sample selection bias also influences the prevalence rates.

Association of furunculosis and familial deficiency of mannose-binding lectin.

BACKGROUND: Polymorphisms in the mannose-binding lectin gene reduce serum mannose-binding lectin levels and are associated with enhanced risk of infection. In a family with recurrent staphylococcal disease presenting as furunculosis or carbuncles, an association with mannose-binding lectin deficiency was investigated. MATERIALS AND METHODS: Levels of functional mannose-binding lectin were estimated and the genotypes of the mannose-binding lectin gene were analysed on blood samples, collected from the members of one particular family with a high prevalence of furunculosis. RESULTS: Functional mannose-binding lectin levels in sera of 13 of the 28 members of one family showed deficiency. Furunculosis or carbuncles appeared to be present in nine of the 28 family members, seven of which showing the pBly allele and mannose-binding lectin deficiency. Four young family members of the second generation were pBly positive and mannose-binding lectin deficient, but had not shown furunculosis yet. CONCLUSION: Members of a particular family suffering from furunculosis differ from their 'healthy' relatives as to mannose-binding lectin genotypes, indicating the relevance of normal mannose-binding lectin levels in the defence against staphylococcal disease.

PR and OTc interval prolongation on the electrocardiogram after binge drinking in healthy individuals.

BACKGROUND: Acute, excessive alcohol intake has been associated with an increased cardiovascular mortality in otherwise healthy individuals. It predisposes to accelerated atherosclerosis resulting in acute coronary events but also arrhythmias have been described, such as atrial fibrillation and life-threatening re-entrant ventricular arrhythmias. QTc prolongation is associated with an increased risk of ventricular tachyarrhythmias and an independent risk factor for sudden cardiac death. The aim of the study is to investigate the effect of binge drinking on the conduction intervals in healthy individuals. METHODS: Ten of the volunteers drank red wine while the other ten volunteers drank a sweet designer drink. A follow-up of blood pressure, heart rate, ECG and laboratory findings was performed at an ethanol level of 0, 0.4 and 0.8%, respectively. RESULTS: Fifteen volunteers showed a prolongation of the PR interval, 13 of the QRS complex, 9 of the QT interval and 13 of the QTc interval. PR interval increased from 149 +/- 16 ms to 163 +/- 11 ms (p < 0.05). The heart rate-adjusted QT interval increased from 400 +/- 24 ms to 426 +/- 52 ms (p < 0.05). Heart rate and systolic blood pressure did not significantly change due to the ingestion. CONCLUSION: Acute ingestion of alcohol in a healthy population can induce prolongation of PR and QTc interval.

Alcohol and polyphenolic grape extract inhibit platelet adhesion in flowing blood.

BACKGROUND: Moderate and prolonged alcohol consumption has been associated with decreased cardiovascular morbidity and mortality. Inhibition of platelet function in suspension attributes to these effects. Whether alcohol, red wine, or polyphenolic grape extracts (PGE) inhibit platelet adhesion is not known. We investigated platelet adhesion to fibrinogen and collagen in whole blood under standardised flow. MATERIALS AND METHODS: Before perfusion was started, citrated whole blood from 95 volunteers was preincubated for five min with different alcohol concentrations, unfractioned red wine and PGE. Then, blood was perfused in a single-passage flow chamber over coverslips coated with human fibrinogen or collagen type III at shear rates of 300 s(-1) and 1600 s(-1). RESULTS: Alcohol inhibited platelet adhesion to human fibrinogen at high shear rate (concentrations > or = 0.15 per thousand) and low shear rate (only at a concentration of 4.8 per thousand), whereas red wine (concentrations > or = 0.15 per thousand) inhibited platelet adhesion to human fibrinogen at both shear rates. In contrast, PGE (concentrations > or = 0.0225 g L(-1)) inhibited platelet adhesion to human fibrinogen only at low shear rate. None of these incubations affected adhesion to collagen. CONCLUSIONS: Alcohol, red wine and PGE inhibit adhesion to fibrinogen but not to collagen. This inhibition might contribute to the cardioprotective effects of moderate alcohol consumption.

Does physical training increase insulin sensitivity in chronic heart failure patients?

To determine the effect of training on insulin sensitivity (IS) and how this relates to peak V(.)O(2) (peak oxygen uptake) in CHF (chronic heart failure), 77 CHF patients (New York Heart Association class, II/III; men/women, 59/18; age, 60+/-9 years; body mass index, 26.7+/-3.9 kg/m(2); left ventricular ejection fraction, 26.9+/-8.1%; expressed as means+/-S.D.) participated in the study. Patients were randomly assigned to a training or control group (TrG or CG respectively). Sixty-one patients completed the study. Patients participated in training (combined strength and endurance exercises) four times per week, two times supervised and two times at home. Before and after intervention, anthropometry, IS (euglycaemic hyperinsulinaemic clamp) and peak V(.)O(2) (incremental cycle ergometry) were assessed. Intervention did not affect IS significantly, even though IS increased by 20% in TrG and 11% in CG (not significant). Peak V(.)O(2) increased as a result of training (6% increase in TrG; 2% decrease in CG; P <0.05). In both groups (TrG and CG), the change in IS correlated positively with the change in peak V(.)O(2) ( r =0.30, P <0.05). Training resulted in an increase in peak V(.)O(2), but not in IS. Whether physical training actually increases IS in CHF patients remains unclear.

Determinants of insulin sensitivity in chronic heart failure.

OBJECTIVE: To describe the determinants of insulin sensitivity (IS) in chronic heart failure (CHF), we created a model in which the influence of lifestyle factors and etiology of heart failure on IS were incorporated concomitantly with age, left ventricular ejection fraction (LVEF) and parameters of body composition. DESIGN: Observational cohort study. SETTING: Outpatient clinic for chronic heart failure. PATIENTS: Fifty-seven male CHF patients [NYHA class II-III, age 61+/-9 years, body mass index (BMI) 26.9+/-3.3 kg/m2 (mean+/-S.D.)]. INTERVENTIONS: Euglycemic hyperinsulinemic clamp, cycle ergometry, anthropometric measurements, LVEF and a physical activity questionnaire. MAIN OUTCOME MEASURES: A model explaining the variance of IS in CHF. RESULTS: IS was 18.2+/-8.6 microg.kg(-1).min(-1).mU(-1).l(-1), fasting insulin level was 15.9+/-11.0 mU/l and fasting glucose level was 5.5+/-0.6 mmol/l. Peak VO2 was 19.1+/-4.9 ml.kg(-1).min(-1) and LVEF 26.2+/-7.1%. IS was inversely associated with fasting insulin concentration (r=-0.50, P<0.001) and BMI (r=-0.54, P<0.001). After controlling for BMI, IS also revealed a correlation with age (r=-0.36, P<0.01). The model explained 60% of variance in IS: BMI contributed 20%, smoking 17%, age 17% and physical activity in daily life (DPA) 16% (all P<0.05) to the variance of IS, whereas LVEF (9%) and etiology of heart failure (8%) contributed moderately. CONCLUSIONS: In CHF patients, IS is for a major part predicted by BMI, smoking, age, daily physical activity, LVEF and etiology of heart failure.

Red wine and red wine polyphenolic compounds but not alcohol inhibit ADP-induced platelet aggregation.

Background: Moderate alcohol consumption reduces the risk of cardiovascular diseases, especially coronary heart disease (CHD). Because of the presence of polyphenols in red wine, this type of beverage may be superior to other alcoholic drinks in the prevention of CHD. Inhibition of platelet aggregation is thought to be one of the mechanisms underlying this favorable effect. The present study analyzes the direct effect of alcohol and red wine polyphenols on platelet aggregation. Methods: Unfractionated red wine, a red wine polyphenolic extract, and alcohol were added in different concentrations to a standardized quantity of blood platelets 2 min before aggregation was induced by different concentrations of ADP. Aggregation was measured in an aggregometer and results were compared to a control 0.9% NaCl solution. Results: Alcohol in concentrations up to 0.24 percent did not inhibit platelet aggregation in vitro initiated with ADP The polyphenolic red wine extract inhibited aggregation dose-dependently and significantly from concentrations of 45 mg/l ( [Formula: see text] ) or more. Red wine only inhibited platelet aggregation at very high concentrations ( approximately 0.24 and 0.48 alcohol%). Conclusions: Consumption of red wine has an inhibitory effect on platelet aggregation, which is caused by the polyphenolic compounds in the wine. Alcohol itself does not have a direct inhibitory effect within a range up to 0.24 percent. Since this effect is only observed at very high concentrations, it is unlikely to be of clinical relevance in a moderate drinking pattern. The results do not exclude platelet inhibition by wine in vivo. However, this must be related to metabolic changes rather than to direct blockade.

Regular alcohol intake and fibrinolysis.

BACKGROUND: Light to moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Stimulation of fibrinolysis has been suggested as one of the mechanisms involved. The present study analyses the effect of regular alcohol consumption on various parameters of fibrinolysis. The question whether the alcohol-induced plasma increase of plasminogen activator inhibitor (PAI-1) may originate from thrombocytes was also addressed. METHODS: Six healthy male volunteers consumed three glasses of red wine daily during two periods of a week, with a week of abstinence from alcohol in between. PAI-1 antigen and activity levels, t-PA antigen and activity levels and plasmin antiplasmin (PAP) complexes were measured on days 1, 3, 8, 15, 17 and 22 of the experiment period. On the first day, PAI-1 antigen and activity before and after alcohol consumption was also measured in platelet-rich plasma (prp). RESULTS: Although some slight shifts in the various parameters could be noticed during the drinking periods, all favouring impairment rather than stimulation, no significant effect of regular moderate alcohol use could be observed on fibrinolysis. Alcohol did not trigger a release of PAI-1 from platelets. CONCLUSIONS: Regular moderate alcohol consumption has no significant effect on fibrinolysis. The alcohol-induced increase of plasma PAI-1 does not originate from thrombocytes. The cardioprotective effect of moderate alcohol consumption cannot be explained by a beneficial influence on fibrinolysis.

[Ketoacidosis after cessation of chronic alcohol consumption]. / Ketoacidose na staken van langdurig alcoholgebruik.

A 52-year-old man was admitted with diarrhea, near dehydration and dyspnoea. After many years of alcohol consumption, he had stopped drinking alcohol over a very short space of time and had eaten very little or nothing. He had tachypnoea, hypotension and an enlarged liver. Laboratory analysis revealed metabolic acidosis with an elevated anion gap, ketone bodies in the urine, increased free fatty acid levels and beta-hydroxybutyrate in the serum, fitting the picture of alcoholic ketoacidosis. The syndrome is explained by metabolic changes induced by chronic alcohol consumption and ketogenesis as the result of fasting and dehydration. Treatment consisted of correction of the fluid deficit and administration of glucose, after which the patient made a rapid recovery.

Statins and the stroke-cholesterol paradox.

Although strokes belong to the group of cardiovascular disorders, there is no clear association between LDL and/or HDL levels and 'stroke' as an entity. However, there is ample evidence that statins reduce stroke risk in selected patient groups such as survivors of myocardial infarction. This apparent paradox can be explained on the one hand by the heterogeneity of strokes as a group and on the other hand by the specific characteristics of statins. There are strong indications for a relationship between blood lipid profiles and types of stroke that have atherosclerosis as the underlying pathogenetic mechanism. Apart from their ability to reduce LDL levels significantly, statins have a number of other properties, which influence the process of atherosclerosis at various stages. Future and ongoing trials have to prove which patients at risk for stroke will benefit most from the preventive use of statins.

[How much alcohol is too much and why? Comments on socially accepted but excessive alcohol drinking patterns]. / Hoeveel alcohol is te veel en waarom? Kanttekeningen bij sociaal geaccepteerd overmatig alcoholgebruik.

Many modern societies increasingly seem to accept drinking patterns that should be qualified as excessive from a health care point of view. This does not concern alcoholism or alcohol addiction but a daily intake of three to eight glasses and the pattern of binge drinking. Although a lot of data are available on the physical consequences of alcohol abuse, little is known about the impact of these drinking patterns on peoples' health. According to the J-shaped curve between alcohol consumption and mortality, an increase in morbidity and mortality can be noticed from two to three drinks a day. This is largely caused by an increase in accidents, malignancies, cardiovascular diseases and neurological disorders. However, data on pathophysiological mechanisms and on the contribution of these drinking patterns in medical consumption are scarce. Because of the estimated extent of the problem and societies' interest, more support should be given to scientific programs and research into this matter. This may not only contribute to a better monitoring of the problem but also guide the development of strategies for education and prevention.

[Nutrition and health--favorable effect of wine and wine flavonoids on cardiovascular diseases]. / Voeding en gezondheid--gunstig effect van wijn en wijnflavonoïden op hart- en vaatziekten.

Epidemiological studies have shown a favourable effect of moderate alcohol consumption with regard to atherosclerotic disorders. In addition to alcohol, wine contains a large number of other components including polyphenols. These polyphenols mainly originate from the skins and seeds of grapes and, because of differences in vinification, their variety and concentration is higher in red wine than in white wine. In vitro and ex vivo studies have shown that some of these polyphenols are able to slow down LDL-cholesterol oxidation, stimulate NO production, influence prostaglandin synthesis and inhibit platelet aggregation. However, little is known about their resorption, bioavailability and effectiveness in vivo. Since data from intervention studies with wine polyphenols are also lacking, no statement can yet be made about any clinically relevant effect of these components, in either red or white wine, in terms of cardiovascular diseases.

Blessings of the grape.

Numerous epidemiological studies have shown an inverse correlation between moderate consumption of alcoholic drinks and the risk of coronary heart disease. Wine, especially red wine, may be more favorable in this respect than beer or spirits because of its high content of flavonoids. These polyphenols originate from the skins, seeds, and vine stems of the grapes while some are formed during the process of vinification. In nature they exhibit a wide range of biological effects as antioxidants, antimicrobials, and modulators of various enzyme systems. Potential beneficial effects for humans have been demonstrated in experimental studies and include influences on the oxidation of LDL-cholesterol, on platelet aggregation, and on prostaglandin and nitric oxide metabolism. However, most of these studies concern semi in vivo experiments and research in animal models; data from human intervention trials are scarce. Furthermore, little is known about the absorption, bioavailability, and bioactivity of most of these compounds because of difficulties in reliable quantification in biological fluids. Until these issues are well addressed, and despite the enthusiasm and faith of many believers, evidence-based medicine justifies a critical attitude towards the application of these compounds outside the context of scientific research. Yet, there is no need to deny their potential, nor should we close our eyes to the blessings of the grape.

Acute inhibitory effect of alcohol on fibrinolysis.

In contrast to a reduced risk of coronary heart disease (CHD) with light to moderate alcohol consumption, heavy alcohol intake and binge drinking are associated with increased cardiovascular mortality. Alcohol has an acute and profound effect on fibrinolysis that may be relevant to the pathogenesis of CHD. The short-term effects of a low (two glasses, 250 mL, 20 g ethanol) and a high (six glasses, 750 mL, 60 g ethanol) intake of red wine were studied in male volunteers and compared to the intake of mineral water. To find a threshold for inhibition of fibrinolysis and to study a binge effect, a second experiment was performed comparing the intake of four (500 mL, 40 g ethanol) and eight (1000 mL, 80 g ethanol) glasses of red wine with mineral water. Plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (t-PA), plasmin-antiplasmin (PAP) complexes and clot lysis time were measured. In contrast to the circadian rhythm with an enhanced fibrinolysis in the evening that was found in the mineral water group, an intake above four glasses of wine inhibited fibrinolysis significantly. After the intake of two glasses no significant disturbance of the circadian rhythm was observed. Five hours after the consumption of six glasses of wine, a dramatic increase occurred of PAI-1 antigen (77 +/- 42 microg L-1 vs. - 5 +/- 10 microg L-1 in the mineral water controls; P < 0.001) and PAI-1 activity (27 +/- 15 U mL-1 vs. - 2 +/- 3 U mL-1 in mineral water controls; P < 0.001). Despite a rise in t-PA antigen, t-PA activity dropped (- 0.5 +/- 0.2 U mL-1 vs. - 0.1 +/- 0.2 in controls; P < 0.001) as did PAP complexes (- 103 +/- 55 microg L-1 vs. - 26 +/- 57 microg L-1 in controls; P < 0.01). After the consumption of eight glasses of wine, the clot lysis assay indicated continued inhibition of fibrinolysis the following morning. Drinking a large amount of alcohol in the evening results in an acute inhibition of fibrinolysis, persisting the following morning. This may predispose to accelerated atherosclerosis and set the stage for thrombotic coronary events, explaining the higher cardiovascular mortality risk in binge drinkers.