Do temporal arteritis lesions contain bacterial DNA?

BACKGROUND: Temporal arteritis is a primary vascular inflammatory disease. The aetiology of temporal arteritis is unknown, but the influence of environmental factors such as infections has been suggested. MATERIALS AND METHODS: We used broad-range PCR, targeting conserved regions of the gene encoding for ribosomal RNA, to detect bacterial DNA in 27 temporal artery biopsies. Five uninvolved temporal arteries were also included. A lung sample of confirmed bacterial pneumonia served as a positive control. Inflammation was examined by histochemistry and light microscopy. RESULTS: The sensitivity of the broad-range PCR assay was 5.0 fg of DNA. Bacterial DNA sequences were neither detected in 27 temporal arteritis specimens nor in the normal temporal artery samples. However, bacterial DNA was successfully amplified from the lung sample of a subject with pneumonia. In addition, human DNA was amplified by primers for human beta-actin from all clinical specimens, suggesting lack of significant inhibitors of the molecular amplification reaction. Histochemistry showed signs of strong inflammation in the arteritis samples. CONCLUSIONS: The lack of detectable amounts of bacterial DNA suggests that viable bacteria do not have a role in chronic stages of temporal arteritis. However, these findings do not rule out the possibility of bacterial degradation products as stimulants of chronic inflammation, or of viable microbes as triggering factors of acute temporal arteritis.

Trends in serum cholesterol and lifestyle indicators in Members of the Finnish Parliament.

OBJECTIVE: To examine the extent that public health promotion activity is reflected in life styles of national decision makers, by analysing trends in coronary heart disease risk factors in Members of the Finnish Parliament (MPs). METHODS: The MPs were studied at the beginning of two subsequent 4-year parliamentary periods between 1991 and 1999. The studies included analyses of serum total cholesterol and high-density lipoprotein (HDL) cholesterol, and a questionnaire about alcohol, smoking and physical activity. RESULTS: Serum total cholesterol was above the national recommendation of 5.0 mmol/l in 85% of the male MPs and 62% of the female MPs. The mean level of serum total cholesterol increased in female MPs during the 4-year follow-up period (P < 0.05), and male MPs showed an increase in mean HDL cholesterol (P < 0.001). The mean body mass index increased in both male (P < 0.01) and female (P < 0.01) MPs during the same period. Alcohol consumption, smoking and physical activity were unchanged during follow-up. CONCLUSIONS: From the public health perspective, serum cholesterol is too high in most MPs, and the level in males is above the national average. Both males and females put on weight during the parliamentary period, and male MPs also showed an increase in HDL cholesterol, which may be explained by other lifestyle factors.

Effect of type of alcoholic beverages on carbohydrate-deficient transferrin, sialic acid, and liver enzymes.

BACKGROUND: There are only limited data obtained under well controlled conditions on the effects of moderate drinking on markers of alcohol use disorders. The aim of this study was to investigate the effects of moderate intake of different alcoholic beverages on these markers, including carbohydrate-deficient transferrin (CDT), sialic acid (SA), and the liver enzymes gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase. METHODS: Eleven apparently healthy, nonsmoking middle-aged men were included in a 12-week randomized, diet-controlled crossover trial according to a 4 x 4 Latin-square design. Changes in CDT, SA, gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase were analyzed after 3 weeks of daily intake of four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or water (control). RESULTS: After 3 weeks' daily consumption of red wine, a significant decrease of serum CDT concentration was observed compared with water consumption. There was no effect of any alcoholic beverage on the other outcome measures. CONCLUSIONS: Daily consumption of 40 g of alcohol from different types of alcoholic beverages with dinner did not affect SA or liver enzymes. Further investigations to explore the mechanisms for the red wine-induced decreases of CDT, including changes in iron metabolism, are clearly needed.

Serum matrix metalloproteinase-9 concentration in angiographically assessed coronary artery disease.

Expression of several matrix metalloproteinases (MMPs) in atherosclerotic plaques has been well documented, and there are findings to indicate that arterial inflammation is reflected in increased serum concentration of matrix metalloproteinase-9 (MMP-9). In coronary atherosclerosis, there is enhanced expression of this MMP, which may be predictive of the severity of the disease. We determined the concentrations of serum MMP-9 in 61 patients (47 males, 14 females) who had >50% obstruction in one or more coronary arteries as assessed by coronary angiography before bypass surgery. In a control group of 19 patients (9 males, 10 females) there were no pathological findings in coronary angiography. ANOVA showed that serum MMP-9 concentrations were highest in patients with 3-vessel coronary artery disease (CAD) (57.3+/-39.1 microg/L, p=0.011). The difference remained statistically significant after adjustment for age, diabetes and sex (p=0.025, ANCOVA). When the groups were compared with each other, serum MMP-9 concentration was higher in the patients with 3-vessel CAD than in those with 1- or 2-vessel CAD (40.4+/-25.1 microg/L, p=0.044) or in the controls (32.2+/- 16.1 microg/L, p=0.007). These results show that serum MMP-9 is elevated in patients with severe coronary stenosis compared with controls. Since MMP-9 has been suggested to reflect inflammation in atherosclerotic plaques, it may be useful in the evaluation of the severity of cardiovascular disease.

Matrix metalloproteinase-9 is elevated in serum of alcohol abusers.

BACKGROUND: Moderate alcohol consumption has been shown to protect against coronary heart disease. However, excessive alcohol use has been suggested to have detrimental effects on the cardiovascular system. We examined whether there is an association between alcohol abuse and circulating levels of matrix metalloproteinase-9 (MMP-9), which has been linked to unstable coronary heart disease and arterial inflammation. DESIGN: Serum MMP-9 concentrations were compared between 40 male alcoholics (mean age 42 years) with ethanol consumption > 1000 g week(-1) and 40 social drinker males with an ethanol consumption of < 200 g week(-1) (mean age 45 years). RESULTS: The mean serum MMP-9 concentration was significantly higher in sera of alcoholics compared to control subjects (70.9 +/- 47.7 g L(-1) and 43.1 +/- 19.2 g L(-1), respectively; P = 0.001). Within the alcoholic group, MMP-9 concentration did not correlate with age, gamma glutamyl transferase, carbohydrate-deficient transferrin, aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase. CONCLUSION: Our finding of elevated MMP-9 concentrations in sera of chronic alcohol abusers helps understand the mechanisms of cardiovascular risk among these subjects.

Association of serum MMP-9 with autoantibodies against oxidized LDL.

Monocyte-derived macrophages in atherosclerotic plaques secrete matrix metalloproteinases (MMPs), which may contribute to plaque rupture. There has been much speculation as to which factors precipitate in the arterial inflammation. Oxidized low density lipoprotein (oxLDL) has been suggested to have proinflammatory properties, and it has been shown to increase matrix metalloproteinase-9 (MMP-9) secretion by macrophages in vitro. We determined serum MMP-9 concentration and autoantibodies against oxLDL by ELISA in men with angina pectoris (n=243) and age-matched controls (n=238). The association between serum MMP-9 concentration and autoantibodies against oxLDL was evaluated. Autoantibody level against oxLDL, expressed in optical density units, was significantly higher in subjects with angina pectoris compared to controls (0.100+/-0.064 versus 0.088+/-0.051, respectively, P=0.030), but serum levels of MMP-9 did not differ significantly between these groups (54.2+/-29.9 versus 50.6+/-23.1 microg/l). However, autoantibodies against oxLDL correlated positively with serum MMP-9 (r=0.21, P<0.001). In a multiple regression model (including age, diastolic blood pressure, cholesterol, HDL cholesterol, triglycerides, BMI, smoking and MMP-9) serum MMP-9 (beta=0.200, P<0.001) and smoking (beta=0.179, P<0.001) were significantly associated with autoantibodies against oxLDL. In conclusion, autoantibodies against oxLDL were positively associated with angina pectoris and serum MMP-9. Since autoantibody level against oxLDL could be expected to reflect the degree of oxLDL in the vessel wall, our results suggest that oxLDL is associated with MMP-9 in vivo.

The role of biomarkers in alcoholism medication trials.

BACKGROUND: Increasingly, biomarkers are being incorporated into the research design of clinical trials on medications to reduce drinking in alcoholics. To date, however, there has been little analysis of the unique roles that biomarkers can play in such investigations or of the practical and conceptual considerations that surround their best use in this context. METHODS: Clinical trials of alcoholism medications published between 1985 and the present were abstracted to determine how biomarkers were used and how changes in them related to self-report measures of drinking. RESULTS: Six uses of biomarkers were identified: determination of subjects to be included or excluded in the trial; description of baseline sample characteristics; primary and secondary outcome assessment; corroboration of self-reports of drinking status; specification of patients likely to respond to the medication; and evaluation of drug safety. CONCLUSION: Use of biomarkers in such studies appears warranted, particularly as an objective source of information on treatment efficacy that can be considered with patient self-report measures of drinking status. Biomarkers related to liver functioning also can assist in determination of drug safety for medications metabolized by the liver.

Serum homocysteine does not associate with uncomplicated coronary heart disease.

BACKGROUND: Elevated serum homocysteine concentrations have been related to coronary heart disease. However, the association has not indisputably been proven, and the mechanisms by which homocysteine may be atherogenic have only partially been elucidated. The objective of the present study was to investigate whether serum homocysteine is associated with angina pectoris and myocardial infarction. METHODS: We compared serum homocysteine concentrations in subjects with clinical evidence of angina pectoris or history of myocardial infarction to age-matched controls. The study included 248 males, who participated in a large cross-sectional risk factor survey carried out in five geographic areas in Finland. RESULTS: Serum homocysteine concentration was significantly higher in subjects with a history of myocardial infarction compared to controls (15.3 micromol L-1 and 13.9 micromol L-1 respectively, P = 0.037). In a logistic regression model including several cardiovascular risk factors, serum homocysteine was significantly associated with myocardial infarction (95% CI 1.0157-1.2990, P = 0.027). Serum homocysteine concentrations did not differ between subjects with angina pectoris and age-matched controls (13.9 micromol L-1 and 14.2 micromol L-1 respectively). CONCLUSIONS: Our results suggest that elevated serum homocysteine is associated with myocardial infarction but not with uncomplicated coronary heart disease.

Association of self-reported diseases and health care use with commonly used laboratory markers for alcohol consumption.

The relationships of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT) and their mathematical combination (gamma-CDT) with self-reported diseases were evaluated in a large cross-sectional risk factor survey. Significant gender effects were observed in associations of the markers with several medical conditions as well as with general health care utilization. In men, CDT was associated with rheumatoid arthritis. In both genders, GGT was positively associated with hypertension and diabetes. gamma-CDT was positively associated with hypertension in males and with asthma in females. This general population study demonstrates that these markers, although most commonly used to assess alcohol misuse, might also serve as health risk indicators.

Brief intervention for male heavy drinkers in routine general practice: a three-year randomized controlled study.

The aim of this research was to evaluate the effectiveness of long-term brief intervention in routine general practice. In five primary care out-patient clinics in a Finnish town, 296 male early-phase heavy drinkers consulting a general practitioner (GP) for various reasons were identified. Control group C (n = 88) was informed of the risks of drinking after the screening and were advised at the subsequent feedback about 2 weeks later to reduce their drinking. Groups A (n = 109) and B (n = 99) were offered in addition seven and three brief intervention sessions, respectively. All GPs took part, whether or not they indicated a special interest. The main outcome measures were differences between beginning and end-point at 3 years in self-reported alcohol consumption, mean corpuscular volume (MCV), and serum carbohydrate-deficient transferrin, aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase. There were no statistically significant differences between study groups A, B and C in mean changes in outcome measures. Within all the groups, MCV decreased. Depending on the outcome measure used and the study group analysed, clinically significant reduction of drinking was found in 25-53% of the subjects. In routine general practice, giving additional sessions of brief intervention may not be as effective as in special research conditions. Factors reducing the effectiveness of brief intervention programmes should be investigated, so that primary health care staff can be better supported in their efforts.

Carbohydrate-deficient transferrin: an aid to early recognition of alcohol relapse.

Although the primary use of biochemical markers of heavy drinking is to assist in screening for alcohol problems, laboratory tests may also aid in early identification of relapse. This report reviews research findings on a new marker, carbohydrate deficient transferrin (CDT), in alcoholics receiving treatment or in follow-up. It also offers recommendations on how CDT may be employed by clinicians monitoring drinking status.

Opinions on alcohol-related issues among professionals in primary, occupational, and specialized health care.

The objective of this study was to analyse differences in health care personnel's knowledge, skills, and attitudes in relation to alcohol-related matters by a postal questionnaire between primary, occupational, and specialized health care. Heavy drinking was considered to be common among patients at all health care levels, and particularly in specialized health care. However, early recognition and treatment of heavy drinkers was considered more appropriate in primary and occupational health care, than in specialized health care. Alcohol consumption was found to be an easy subject to discuss at all health care levels. In addition, 90% (165/183) of the respondents thought that patients had a positive or neutral attitude towards questions on their alcohol consumption. Of the respondents, 32% (58/182) considered discussing alcohol-related matters unacceptable and 81% (121/149) believed that they could not influence patients' drinking using brief intervention; there was no significant difference between different settings. Additionally, motivational skills of doctors and nurses were found to be poor at all health care levels. Our study shows that, although discussing alcohol consumption is easy, better motivational skills and more positive attitudes are needed in primary, occupational, and specialized health care. Professionals need further education at all health care levels, but particularly in specialized health care.

Improved diagnostic classification of alcohol abusers by combining carbohydrate-deficient transferrin and gamma-glutamyltransferase.

BACKGROUND: Biochemical markers can provide objective evidence of high alcohol consumption. However, currently available markers have limitations in their diagnostic performance. METHODS: The diagnostic values of the most frequently used markers [carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume] were studied in an analysis of six different clinical studies (n = 1412) on alcohol abusers and social drinkers. The purpose of the analyses was to determine whether a combination of markers would improve the diagnosis of subjects. RESULTS: Discrimination between alcohol abusers and social drinkers, as measured by the areas under nonparametric ROC plots, was significantly better (P<0.001) for the new combined marker [gamma-CDT = 0.8. ln(GGT) + 1.3. ln(CDT)] than for any of the separate markers or combination of CDT or GGT with other markers. The cutoff values for gamma-CDT (6.5) can be taken to be the same among males and females. CONCLUSIONS: The combined variable gamma-CDT is a powerful tool to discriminate alcohol abusers from social drinkers and is recommended for clinical use.

Possible reasons why heavy drinking increases carbohydrate-deficient transferrin.

BACKGROUND: Transferrin is a globular protein synthesized in the liver that is responsible for iron transport in plasma. The structure of the molecule consists of two carbohydrate residues to which six sialic acid moieties can be attached. After periods of chronic, heavy alcohol consumption, carbohydrate-deficient transferrin (CDT) isoforms often increase, which makes CDT a useful marker in screening for alcohol abuse and monitoring progress of alcoholics in treatment. However, the precise mechanism behind CDT increase remains unknown. METHODS: A review of the most relevant literature on CDT was conducted with a computer-assisted literature search. RESULTS: During the past several years, a number of studies have explored possible mechanisms that may account for the alcohol-induced increase of CDT. An inhibition of protein synthesis and a general effect of alcohol on protein glycosylation have been reported. Although the exact mechanisms that underlie production of CDT are not yet fully understood, possible bases for the phenomenon are presented in this article. CONCLUSIONS: Experimental findings indicate that the ethanol-induced effect on glycoprotein metabolism is a multistep process in which protein transport and changes of enzyme activity may play an important role.

Association of carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) with serum lipid profile in the Finnish population.

BACKGROUND: Moderate consumption of alcohol may reduce mortality from vascular diseases. The beneficial effects of alcohol may partly be mediated by its effects on lipoprotein metabolism. We studied the connection between alcohol consumption and the serum lipid profile from a well-documented national health program study. METHODS AND RESULTS: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. The laboratory analyses were carried out on 5675 subjects (3097 males and 2578 females). The subjects were divided into quartiles on the basis of CDT or GGT value. The highest CDT quartile and the lowest GGT quartile seemed to be associated with a favorable lipid profile and the lowest CDT quartile and the highest GGT quartile were associated with an unfavorable lipid profile. Serum high density lipoprotein (HDL) cholesterol values were significantly higher and triglycerides lower with increasing serum CDT concentrations for both men and women. Increasing serum GGT was associated with higher serum total cholesterol and higher triglycerides in both men and women and lower HDL cholesterol in men. CONCLUSIONS: CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may lead to a better understanding of the effects of alcohol consumption on lipids as well as mechanisms behind favorable and detrimental effects of alcohol on vascular diseases. CONDENSED ABSTRACT: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyl-transferase (GGT) were used as biochemical markers for alcohol consumption. A total of 3097 males and 2578 females were divided into quartiles on the basis of their CDT or GGT values. The highest CDT quartiles had higher HDL and lower triglycerides, whereas the highest GGT quartiles appeared to be associated with higher total cholesterol and triglycerides in both genders and lower HDL in men. CDT and GGT seem to detect different populations of subjects in regard to lipid metabolism. These observations may have important clinical and public health implications.

Brief intervention for female heavy drinkers in routine general practice: a 3-year randomized, controlled study.

BACKGROUND: Today, heavy drinking is a common health hazard among women. The evidence in favor of providing some kind of brief intervention to reduce drinking is quite convincing. However, we do not know if intervention works in a natural environment of routine health care. The purpose of this study was to evaluate the effectiveness of long-lasting, brief alcohol intervention counseling for women in a routine general practice setting. METHODS: In five primary care outpatient clinics in a Finnish town, 118 female early-phase heavy drinkers who consulted their general practitioners for various reasons were given brief alcohol intervention counseling. Intervention groups A (n = 40) and B (n = 38) were offered seven and three brief intervention sessions, respectively, over a 3-yr period. The control group C (n = 40) was advised to reduce drinking at baseline. Main outcome measures were self-reported weekly alcohol consumption, carbohydrate-deficient transferrin, mean corpuscular volume (MCV), aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase. RESULTS: Depending on the outcome measure and the study group, clinically meaningful reduction of drinking was found in 27% to 75% of the heavy drinkers. Within all the groups, MCV significantly decreased. However, there were no statistically significant differences between study groups A, B, and C in the mean changes between the beginning and endpoint in the main outcome measures. CONCLUSIONS: The present study indicated that minimal advice, as offered to group C, was associated with reduced drinking as much as the brief intervention, as offered to groups A and B, given over a 3-yr period. Furthermore, in the routine setting of the general practice office, the effectiveness of the brief intervention may not be as good as in special research conditions. The factors possibly reducing the effectiveness in a routine setting are unknown. Thus, different methods of implementing brief intervention need to be evaluated to find better ways to support general practice personnel in their efforts to help heavy-drinking female patients to reduce their drinking.

Effect of hormone balance on carbohydrate-deficient transferrin and gamma-glutamyltransferase in female social drinkers.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) are the most commonly used markers for alcohol abuse, but their sensitivity and specificity are lower and have different reference values among females compared with males. In the present study, we evaluated the effect of women's hormone balance on these two alcohol markers, as well as on their mathematical combination, named gamma-CDT. METHODS: An age-stratified random sample of 3962 women, between 25-74 years old, was drawn from the normal population. Pregnancy, the use of oral contraceptives, intrauterine device for contraception, hormone replacement therapy, and hormone treatment for infertility were considered. A comparison between fertile, peri- and postmenopausal women was also done. RESULTS: Existing pregnancy increased CDT levels but decreased GGT values. Lower CDT and higher GGT levels were observed among those women using oral contraceptives and in postmenopausal women compared with women at the fertile stage. gamma-CDT was not influenced by hormone balance. CONCLUSIONS: The different hormonal status had an opposite effect on CDT and GGT. Women who were close to late menopause had levels of both markers closer to the values of men. It must be pointed out that the findings presented here are based on measurements of absolute CDT values and that no measurements of total transferrin were done. gamma-CDT, not influenced by hormone balance, indicates promising clinical utility among women.

Dose response of laboratory markers to alcohol consumption in a general population.

The dose response to alcohol use of carbohydrate-deficient transferrin (CDT), gamma-glutamyltransferase (GGT), and their combination (gamma-CDT) was studied in an age- and gender-stratified, random sample from Finland in 1997. A linear association with a threshold between alcohol consumption and the three markers was observed. Body mass index was negatively associated with CDT and positively with GGT Age was positively associated with GGT and gamma-CDT In conclusion, CDT appears to be an early phase marker of alcohol consumption. The combined marker, gamma-CDT, was less associated with factors such as body mass index but more strongly correlated with alcohol consumption than were the two markers separately.

Alcohol consumption and its relation to lipid-based cardiovascular risk factors among middle-aged women: the role of HDL(3) cholesterol.

To study the association of alcohol consumption and lipid-based cardiovascular risk factors among middle-age women, cross-sectional analysis among 274 middle-aged healthy women with different drinking habits and a follow-up analysis of alcoholic women during abstinence was performed. Serum total cholesterol, low and high-density lipoprotein cholesterol (LDL and HDL cholesterol), triglycerides (TG), apolipoproteins A1 (Apo A1) and B (Apo B), and HDL-cholesterol subfractions 2 (HDL(2)) and 3 (HDL(3)) were measured. All lipid values except LDL cholesterol positively correlated with self-reported alcohol consumption. When alcoholics were excluded the correlation was significant only for HDL cholesterol, HDL(3), and Apo A1. The increasing trend of HDL cholesterol, HDL(3) and Apo A1 were clearly seen first in women consuming >20-40 g/day of absolute alcohol. Alcohol consumption >40 g/day increased all lipid values except LDL cholesterol. Abstinence for 2 weeks caused a significant decrease in HDL(3) cholesterol, and an increase in LDL cholesterol and Apo B. The results indicate that among middle-aged women the Apo A1 and HDL cholesterol via its HDL(3) but not HDL(2) subfraction might play a role in the beneficial coronary consequences associated with moderate alcohol consumption. However, the increasing beneficial trend first appears when daily drinking exceeds 20 g/day.

Enhanced clinical utility of gamma-CDT in a general population.

BACKGROUND: The use of a combination of markers to detect excessive alcohol consumption has been reported to provide better sensitivity in the diagnosis of alcohol abuse than single markers. However, the optimal combination of markers for the diagnosis of alcohol abuse has not yet been found. The aim of this study was to compare the diagnostic value of carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) to discriminate among heavy drinkers (>280 g/week), moderate drinkers (105-280 g/week), and light drinkers (<105 g/week). Their mathematical combination, named gamma-CDT, which has been found to be a strong marker of alcohol abuse in a former study, was also evaluated. METHODS: The study was conducted in a group of 6962 subjects (3974 males and 2988 females), between the ages of 25 and 74 years, who participated in a large cross-sectional risk factor survey carried out in five geographic areas in Finland. In each study area, an age- and gender-stratified random sample was drawn from the general population. Sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic curves were used to evaluate the performance of CDT, GGT, and gamma-CDT. RESULTS: For both sexes, the combined marker had the highest specificity (95%) and sensitivity in detecting heavy drinkers. In all cases, gamma-CDT had the highest area under ROC plots. Our results also showed that GGT and CDT have similar, and rather low, sensitivity but high specificity in a general population. CONCLUSIONS: Compared with single markers, a significant improvement of sensitivity was obtained when the combination of both markers was used, especially in females.