Molecular identification of 13 new enterovirus types, EV79-88, EV97, and EV100-101, members of the species Human Enterovirus B

Paired PBMCs and plasma samples from 34 HIV-infected patients were studied to verify the relationship between coreceptor use based on genotyping of V3 region of HIV-1 envelope gp120 and biological phenotype with virus isolation and subsequent correlation to clinical characteristics. The “11/25” rule, geno2pheno and PSSM were compared. All SI patients were HIV-1 subtype B (p = 0.04) and had a lower CD4 count than NSI patients (p = 0.01), while no differences were observed in mean HIV-RNA _log (p = 0.6). SI phenotype was not associated with AIDS-defining events (p = 0.1) or with concurrent antiretroviral therapy (p = 0.4). With geno2pheno, which shows the highest sensibility (83%), an X4 or X4/R5 genotype in PBMC DNA was also associated to B-subtype and lower CD4 count (p = 0.01) compared to R5 isolates. Based on plasma RNA sequences, the predicted coreceptor usage agreed with PBMC DNA in 79% of cases with the “11/25” rule, 82% with geno2pheno, and 82% with PSSM. A X4 virus in plasma (but not in PBMCs) was significantly associated with HAART in all three methods (p = 0.01 for “11/25” rule, p = 0.01 for geno2pheno and p = 0.03 for PSSM). Due to viral mixtures and/or difficulties in genotype interpretation, current V3 sequence-based methods cannot accurately predict HIV-1 coreceptor use.     

A short communication course for physicians improves the quality of patient information in a clinical trial

We investigated whether a short course in communication skills for physicians would improve the quality of informed consent in a randomized clinical adjuvant trial on breast cancer. In this prospective, case-controlled intervention study, physicians and research nurses who introduced the cancer treatment trial to patients at three of the participating hospitals first attended a one-day communication skills course. The quality of informed consent was then evaluated by addressing a standardized questionnaire, QuIC, to trial patients at the three intervention hospitals and at control hospitals. Response rate was 90.0% (n =288). Of the patients treated by the intervention group, 73% were very satisfied with the information received compared with 56% of those of the control group (p = 0.003). The patients of the intervention group considered the time given for making their decision sufficient more often than those of the controls (98% vs. 90%, p=0.004). The patients of the intervention group recalled more often than those of the controls that the physician had also offered other therapeutic options than the trial treatment (91% vs. 97%, p=0.032). They also understood the main aim of the study better than the patients of the controls (89% vs. 78%, p=0.030). In conclusion, a short communication skills course for the trial physicians and nurses improved the quality of informed consent and patient satisfaction in the trial.     

Obstacles to carrying out brief intervention for heavy drinkers in primary health care: a focus group study

The objective of this study was to identify possible obstacles to carrying out competent early identification and brief intervention (EIBI) of heavy drinkers in primary health care. Qualitative focus group discussion method study applying the deductive framework approach. Six focus groups involving 18 general practitioners and 19 nurses were recruited from primary health care of the City of Tampere, Finland. Possible obstacles are: (1) confusion regarding the content of early-phase heavy drinking, (2) lack of self-efficacy among primary health care professionals, (3) sense of lacking time needed for carrying out brief intervention, (4) not having simple guidelines for brief intervention, (5) sense of difficulty in identifying of early-phase heavy drinkers, and (6) uncertainty about the justification for initiating discussion on alcohol issues with patients. The main actions to be taken to promote brief intervention are to educate professionals about the content of early-phase heavy drinking and to produce directing, but not excessively demanding guidelines for carrying out EIBI. Probably successful personal experiences carrying out EIBI can improve professionals' self-efficacy and give to them final justification for discussion alcohol issues with their patients.     

Cyclosporine induces myocardial connective tissue growth factor in spontaneously hypertensive rats on high-sodium diet

BACKGROUND: The introduction of cyclosporine (CsA) has led to an improvement in the prognosis of solid organ transplantation. However, drug-induced hypertension and nephrotoxicity, associated with the development of atherosclerosis and coronary heart disease, still worsen the long-term outcome of CsA-treated patients. Whether the CsA-induced myocardial changes are associated with the induction of connective tissue growth factor (CTGF), a recently found polypeptide implicated in extracellular matrix synthesis, is not known. METHODS: Spontaneously hypertensive rats (8-9 weeks old) were treated with CsA (5 mg x kg(-1) x d(-1) subcutaneously) for 6 weeks. The influence of angiotensin-converting enzyme inhibition (enalapril 30 mg x kg(-1) x d(-1) orally) and angiotensin-1 receptor blockade (valsartan 3 and 30 mg x kg(-1) x d(-1) orally) on CsA toxicity was also investigated. Myocardial morphology was examined, and vascular lesions were scored. Localization and the quantitative expression of CTGF, as well as collagen I and collagen III, mRNA were evaluated by in situ hybridization and Northern blot. RESULTS: CsA-induced hypertension and nephrotoxicity were associated with myocardial infarcts and vasculopathy of the coronary arteries. CsA increased myocardial CTGF, collagen I, and collagen III mRNA expressions by 91%, 198%, and 151%, respectively. CTGF mRNA expression colocalized with the myocardial lesions. Blockade of the renin-angiotensin system prevented vascular damage and the CsA-induced CTGF, collagen I, and collagen III mRNA overexpressions in the heart. CONCLUSIONS: CsA increases CTGF, collagen I, and collagen III mRNA expressions in the heart. The induction of CTGF gene is mediated, at least in part, by angiotensin II.     

Effectiveness of the Alcohol Use Disorders Identification Test in Occupational Health Screenings

This study evaluated the effectiveness of the 10-item Alcohol Use Disorders Identification Test (AUDIT) among occupational health screenings. AUDIT was available from 32 male and 93 female employees, mainly of academic organizations; 22 alcoholic men reporting to treatment at a detoxification clinic served as a reference group. Two other structured questionnaires, the Malmö modified Michigan Alcoholism Screening Test (Mm-MAST) and the CAGE, were compared with the AUDIT, and comparisons were also made to the self-reported weekly alcohol consumption. The total score on the AUDIT correlated equally with the self-reported alcohol consumption, especially when the alcoholics were excluded ( r = 0.73, p < 0.001) as the Mm-MAST ( r = 0.58, p < 0.001) and CAGE ( r = 0.33, p = 0.005). All three questionnaires were good at detecting male alcoholics: using the cut-off point of at least 8 positive answers on the AUDIT, 3 on the Mm-MAST, and 3 on the CAGE. The sensitivities were 100%, 100%, and 91%, respectively. In the AUDIT, however, there was a clearer difference related to the cut-off level than with the Mm-MAST and CAGE. With the cut-off of 8 points, 31% of the male and 11 % of the female employees were classified as suspect heavy drinkers. The AUDIT was significantly more often accurate than the two other questionnaires, especially among female employees in detecting suspect early-phase heavy drinkers and thus seems to be suitable for health screenings.     

Macrocytosis as a Consequence of Alcohol Abuse among Patients in General Practice

Macrocytosis, a common finding in patients without anemia or other hematologic abnormalities, is often ignored. The purpose of this prospective study was to investigate 300 consecutive, adult health-center patients with a mean cell volume (MCV) value greater than or equal to 100 fl. The incidence of macrocytosis was 2.4%. Of the 177 male and 123 female patients, only 14 (4.7%) were anemic; 80.2% of the men (89.3% of those under 60 years) and 34.1% of the women were alcohol abusers, representing the largest diagnostic group. The highest MCV value found in alcoholics without folate or vitamin B12 deficiency was 120 fl. The most useful laboratory test for identifying alcohol abuse among macrocytic patients was the measurement of serum gamma-glutamyltransferase. Of the several morphologic abnormalities in the marrow the only specific finding were vacuoles in the granulocyte or erythrocyte precursors. No underlying cause was found for macrocytosis in 6.8% of the men and 35.8% of the women. Even when it is not associated with anemia, macrocytosis should not be ignored. It may be the only indicator of a disease which often, particularly in young and middle-aged men, is alcohol abuse.     

Seasonal variation in high density lipoprotein cholesterol

We investigated the seasonal variation in high density lipoprotein cholesterol (HDL) in 142 dyslipidemic (non-HDL-cholesterol ≥ 5.2 mmol/1) middle-aged men in the placebo group of the Helsinki Heart Study over the 5-year trial period. A seasonal pattern was found in HDL fluctuation, with a 4.5% drop during mid-winter (5-year mean 1.192 ± 0.265 mmol/1) compared with a stable level (5-year mean 1.248 ± 0.281 mmol/1) during the rest of the year (P < 0.001). A less pronounced seasonal variation in HDL was observed in 85 subjects receiving gemfibrozil. Although affecting pretrial HDL level in cross-sectional analyses, age, alcohol consumption, dietary adherence, physical activity and serum triglycerides had no influence on the seasonality of HDL variation. Smoking had a slight attenuating effect on the variation pattern. Pretrial HDL was influenced by relative weight, but there was also an inverse relationship between HDL and body weight variations, i.e. the annual drop in HDL coincided with the annual peak in body weight. However, seasonal HDL variation was not directly reflected in the annual variation in CHD incidence.     

CDT by Anion-Exchange Chromatography Followed by RIA as a Marker of Heavy Drinking Among Men

Carbohydrate-deficient transferrin, CDT, had previously been reported to be an excellent marker for alcoholism. The present population-based study examined the diagnostic value of CDT among consecutive middle-aged males including 122 social drinkers (mean alcohol consumption 88 ± 79 g per week) and 77 non-alcoholic heavy drinkers (301 ± 195 g/wk). Ninety-six men with a well-documented history of chronic alcoholism (≥1000 g/wk) were used as a reference group. The CDT (containing mainly isotransferrin with pl = 5.8 and 5.9) was separated by anion exchange chromatography and assayed by RIA. The CDT values of social drinkers (mean ± SD = 14 ± 5 U/I) were significantly lower than those of heavy drinkers (19 ± 13 U/I, p < 0.01) and alcoholics (34 ± 18 U/I, p < 0.001). In the whole material CDT correlated positively with alcohol consumption ( r = 0.53, p < 0.001). At a specificity of 91.8%, CDT found 28.6% of the heavy drinkers and 79.2% of the alcoholics; the best traditional marker, GGT, with a specificity of 86.9%, found 35.1% and 64.6%, respectively. In conclusion, CDT is a specific marker, which is superior to traditional markers for identifying alcoholics. Unfortunately, it does not seem to provide additional power for identifying the important group, non-alcoholic heavy drinkers.     

Selective Acceleration of Auditory Processing in Chronic Alcoholics during Abstinence

Simultaneous auditory processing between the hemispheres was studied with a whole-head magnetometer in 13 abstinent chronic alcoholics and 10 healthy control subjects. Auditory stimuli were presented monaurally with interstimulus intervals of 0.5 and 2.5 sec in different blocks. The N100m response, which contributes to stimulus detection, was significantly accelerated in the hemisphere ipsilateral to the ear stimulated in abstinent alcoholics. The MMNm response reflecting automatic stimulus-change detection peaked earlier in alcoholics, and the ipsilateral N100m latency correlated significantly with the abstinence duration. These results suggest that auditory processing is accelerated in the auditory cortex ipsilateral to the stimulated ear in chronic abstinent alcoholics and that the accelerated processing is at least partly reversible. This may be caused by the hyperexcitation in the brain related to the ethanol withdrawal.     

Carbohydrate-Deficient Transferrin and Conventional Alcohol Markers as Indicators for Brief Intervention among Heavy Drinkers in Primary Health Care

Brief intervention is a promising treatment for heavy drinking. The present study examined the diagnostic value of carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ glutamyltransferase (GGT) in detecting early-phase heavy drinkers for brief intervention treatment in primary health care. Laboratory data were collected from consecutive 20- to 60-year-old, early-phase heavy drinkers (329 males and 136 females), who were willing to undergo brief intervention treatment in five primary health care outpatient clinics. An elevated value of at least 1 of the 5 markers studied was found in 75% of the male and in 76% of the female heavy drinkers. The sensitivities of CDT, MCV, AST, ALT and GGT values were low; in men, respectively, 39%, 28%, 12%, 28%, and 33%. and in women 29%, 40%, 20%, 29%, and 34%. However, marker combinations, including CDT, reached a good level of sensitivity; the best triple combination (CDT or MCV or GGT) was positive in 69% of the men and 70% of the women. According to logistic regression, the age of the patient had an increasing effect on MCV, ALT and GGT. High body mass index increased all transaminases and decreased CDT and MCV. Smoking increased MCV and decreased AST. Thus, primary health care marker combinations, especially those including CDT, should be considered for the detection of early-phase heavy drinkers for brief intervention treatment.