ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01132.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Recent studies in transgenic mice provide strong evidence for a direct anti‐atherogenic role of high‐density lipoproteins (HDL) and highlight the importance of multiple gene interactions in the regulation of HDL levels. Plasma lipid transfer processes mediated by cholesteryl ester transfer protein (CETP) have a major impact on HDL levels, as revealed in studies of human genetic CETP deficiency and CETP transgenic mice. Subsequent to the discovery of an intron 14 CETP gene splicing defect, several new CETP gene mutations have been discovered recently in Japanese and other populations. One of these is an exon 15 missense mutation, changing amino acid 442 of CETP from aspartate to glycine. Population studies in Japan indicate that CETP gene mutations are sufficiently common to have a significant influence on HDL levels in the general population. Studies in transgenic mice show that CETP expression results in decreased levels of HDL cholesterol, but that the effects of CETP on HDL apolipoprotein A‐I (apoA‐I) content and size show important modulation by co‐expression with transgenes encoding human apoA‐I, apoC‐III and apoA‐II. In addition to the apparent antiatherogenic phenotype of human genetic CETP deficiency, high level expression of CETP in transgenic mice leads to accelerated atherosclerosis, illustrating the pro‐atherogenic potential o

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01133.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Objective. To compare the costs and effects of two different intervention strategies for the nonpharmacological treatment of hypercholesterolaemia.Design. Randomized, controlled trial. Subjects were randomly allocated to one of two intervention models and followed up for 1 year.Setting. Vårby Health Centre, a primary care practice located in a suburb of Stockholm.Subjects. Subjects with a total serum cholesterol in the range 7.0–7.8 mmol L−1and no signs of ischaemic heart disease or diabetes mellitus, randomized to a low‐intensity (n= 35) or medium‐intensity (n= 41) intervention.Intervention. Two strategies were used, one labelled medium‐intensity strategy which followed national current guidelines for nonpharmacological treatment of hypercholesterolaemia, the other was a low‐intensity strategy.Main outcome measures. Total serum cholesterol and intervention costs.Results. Both intervention strategies resulted in small (mean 3.5%) decreases in total cholesterol with no significant difference between the groups. The cost per subject in the low‐intensity group was SEK 753 and in the medium‐intensity group SEK 3614.Conclusions. Because the effect of the two intervention programmes did not differ, the low‐intensity programme is to be preferred from a cost‐effectiveness point of view. If only one‐third of the population in Stockholm county with cholesterol levels ≥ 6.5 mmol L−1are discovered by the primary health care system, and follow the treatment advice, the net savings in the low‐intensity model compared to the current guidelines here presented as the moderate‐intensity

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01134.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Objectives. The aim of this study was to carry out a cost‐effectiveness analysis of a multifactorial intervention programme in treated hypertensive patients.Design. A cost‐effectiveness analysis based on 3 years of follow‐up in an open, randomized, parallel‐group study with allocation either to a comprehensive, multiple‐risk‐factor modification programme or to conventional treatment.Setting. An outpatient clinic of a city hospital.Subjects. Inclusion criteria were: male sex, age 50–72 (mean 66.4) years, treated hypertension and at least one of the following: serum cholesterol ≥ 6.5 mmol L‐1, and/or smoking and/or diabetes mellitus. A total of 508 patients were included in the study.Interventions. Advice given to individuals, and group meetings based on nutritional advice and behavioural treatment principles. If necessary, drug therapy could be instituted to achieve the treatment goals in the intervention group: serum total cholesterol of<6.0 mmol L−1, no smoking, HbAlc<6.0% and diastolic blood pressure<90 mmHg in both groups.Main outcome measure. Incremental cost per life‐year gained of the intervention programme.Results. The cost per life‐year gained was SEK 4000 in an estimation based on the observed risk reduction and ranged between SEK 62 000 and SEK 163 000 in three estimations based on the risk factor changes.Conclusions. The analysis indicates that the intervention programme is cost‐effective in the s

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01135.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Objectives. To study the pattern of plasma levels of endotoxin, tumour necrosis factor alpha (TNF‐α), interleukin 6 (IL‐6) and C‐reactive protein (CRP) in febrile neutropenic patients and to assess the potential diagnostic value of these analyses.Design. Consecutive prospective study.Setting. Patients treated at the haematology ward at Danderyd Hospital, Sweden.Subjects. Ninety‐four patients with fever and haematological disease entered the study (male/female: 59/35) with 176 febrile episodes.Interventions. Blood samples were drawn at days 0, 1, 2 and 6 after onset of fever for analysis of, endotoxin, TNF‐α, IL‐6 and CRP.Results. Infectious aetiology was established in 62.5% of the febrile episodes. Blood cultures showed significant growth in 71/176 (40.3%) febrile episodes. Nonbacteraemic bacterial infections were diagnosed in 34/176 (19.3%) episodes. Endotoxin was detected in plasma in 40% of febrile episodes regardless of aetiology. TNF‐α was detected in 61% and IL‐6 in 94% of all febrile episodes. The initial TNF‐α and IL‐6 levels were significantly higher in patients with Gram‐negative bacteraemia than in patients with other causes of fever (P<0.001). In episodes evaluated as successful after empirical antibiotic treatment, a significant (P<0.001) decrease in CRP concentrations were found on day 6 after onset of fever.Conclusions. The sustained, low‐grade endotoxaemia and persistently elevated levels of TNF‐α and IL‐6 found in febrile patients may reflect a failing mucosal barrier that allows endogenous bacterial products to reach the circulation. The diagnostic value of endotoxin, TNF‐α, IL‐6 and CRP to discriminate between bacteraemic and nonbacteraemic febrile episodes was very limited. The study supports the present policy of broad, empirical antibiotic treatment in patients

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01136.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Objectives. To study the cardiovascular effects of human growth hormone (GH) replacement therapy in adults.Intervention. Biosynthetic human GH given in a daily dose of 0.04 ± 0.01 IU kg−1for 6–18 months in an open trial.Patients. Thirty‐four GH‐deficient hypopituitary patients on conventional replacement therapy, aged 19–67 years and with a body mass index of 18.0–410.0 kg/m2.Measurements. Resting blood pressure, exercise tolerance, renal function and routine blood counts were assessed every 6 months. Two‐dimensional echocardiography and Doppler ultrasound scanning were performed at 0, 6 and 12 months of GH therapy.Results. Exercise time increased significantly on GH from 9.37 ± 2.64min at the start to 10.39 ± 2.86 min (P<0.001), 10.90 ± 2.48 min (P<0.001) and 11.11 ± 0.70 min (P<0.001) at 6, 12 and 18 months respectively. There was no change in the heart rate or in the blood pressure at rest nor at the peak of exercise. No significant changes were observed in measures of cardiac structure (left ventricular mass index, left ventricular posterior wall thickness and interventricular septal thickness), ejection fraction nor in cardiac output. Isovolumic relaxation time, a marker of diastolic function, decreased in 24 patients after 6 months on GH (from 98.6 ± 15.9 to 89.6 ± 15.2 ms;P<0.03) but it was not different from baseline in the 18 patients who were restudied at 12 months. There was no significant change in the left ventricular filling neither at 6 nor at 12 months. No significant changes were observed in plasma electrolytes, creatinine nor in blood count on GH treatment.Conclusions. Growth hormone replacement therapy in hypopituitary adults for 6–18 months produced sustained increase in exercise tolerance but was not associated with changes in cardiac structur

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01137.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Objectives. To study whether (i) the low‐density‐lipoprotein (LDL)‐receptor gene mutation type itself or (ii) thePvuII restriction‐fragment‐length polymorphism (RFLP) of the intact LDL‐receptor gene affects serum lipid levels and their responses to lovastatin treatment in heterozygous familial hypercholesterolaemia (FH).Design. Comparison of serum lipid levels in 149 heterozygous FH patients, including 79 patients with the FH Helsinki gene and 70 patients with the FH North Karelia gene, grouped according to thePvuII RFLP status of their nonmutated LDL‐receptor allele; studies of lovastatin responses in 23 FH patients with different mutation types.Subjects. Molecularly defined heterozygous FH patients.Interventions. DNA analysis by polymerase chain‐reaction assay (PCR) and Southern blotting, fasting serum lipid measurements in all patients, and administration of lovastatin 40–80 mg daily to 16 FH Helsinki patients and seven FH North Karelia patients.Main outcome measures. Baseline and post‐treatment serum cholesterol, LDL cholesterol, high‐density‐lipoprotein (HDL) cholesterol and triglyceride levels.Results. There were no significant differences in serum total or LDL‐cholesterol levels in FH patients with the FH Helsinki gene compared with those carrying the FH North Karelia gene. Regardless of the mutation type, patients without thePvuII site in the normal LDL‐receptor gene (P– subjects) tended to have 6–8% higher serum and LDL‐cholesterol levels than patients possessing this restriction site (P+ subjects). Although not statistically significant, this difference is qualitatively and quantitatively similar to that reported in three different non‐FH populations. Treatment with lovastatin brought about similar hypolipidaemic responses in FH patients with either mutation type (FH Helsinki or FH North Karelia) orPvuII RFLP status (P+ orP–).Conclusions. Two LDL‐receptor gene mutations with dissimilar phenotypic characteristics are associated with similar serum lipid levels and response to statin treatment. Our data also support the previous assumption that thePvuII RFLP of the LDL‐receptor gene locus is associated w

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01138.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Objectives. The mortality from coronary heart disease (CHD) is exceptionally low in northernmost Finland, the Sámi (formerly known as Lapp) area. To clarify the reasons for this, the levels of serum cholesterol, other classic risk factors, and major antioxidants, alpha‐tocopherol, retinol, albumin and selenium were determined in males living in the low‐mortality area and in a reference area.Design. A health survey amongst reindeer herdsmen living in the three northernmost communes of Finland (the Sámi area) and in the six neighbouring communities to the south (the reference area). The mortality from CHD in the two areas was determined from death certificates issued during the period 1981–1990.Subjects. A total of 350 participants of the health survey, mean age 46 (SD 14) years.Results. The mortality from CHD was 17% lower in the Sámi area than in the reference area [95% confidence interval (CI) for the difference: 4–29]. Subjects living in the low‐mortality area showed higher serum‐lipid‐adjusted alpha‐tocopherol (18.4 vs. 16.1 μmol L−1; 95% CI for difference: 0.7–3.9;P<0.001), albumin (46.9 vs. 46.2 g L−1; 0.2–1.3;P<0.02), selenium (1.59 vs. 1.47 μmol L−1; 0.02–0.22;P<0.02), cholesterol (6.76 vs. 6.34 mmol L−1; 0.12–0.72;P<0.001) and LDL cholesterol (4.76 vs. 4.45 mmol L−1; 0.05–0.57;P<0.02) than those in the reference area. The HDL cholesterol: cholesterol ratio was lower in the Sámi area than in the reference area (0.20 vs. 0.21; –0.02–0.00;P<0.04). The Sámis showed higher serum selenium than the Finns, Serum alpha‐tocopherol increased with the consumption of reindeer meat and serum selenium increased with fish consumption.Conclusions. Alpha‐tocopherol, albumin and selenium may play a role in the low mortality from CHD observed in northernmost Finland. The favourable serum antioxidant statu

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01139.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Objective. Based on a meta‐analysis, it was recently stated that there is no association between coffee consumption and the risk of coronary heart disease. Why then, have studies on the issue shown quite variable results?Design, setting and subjects. A prospective study was performed in the Copenhagen Male Study on 2975 men (53–74 years) without cardiovascular disease at the baseline in 1985/1986. They were classified according to self‐reported consumption of filter coffee. Some 147 men (5%) were coffee abstainers. Potential confounders were alcohol use, physical activity, smoking, serum cotinine, serum lipids, serum selenium, body mass index, blood pressure, Lewis blood group, hypertension, non‐insulin‐dependent diabetes mellitus and social class.Main outcome measures. The incidence of ischaemic heart disease (IHD) 1985/86–1991.Results. Some 184 men had a first IHD event. There was no significant difference between those consuming 1–4, 5–8 or ≥ 9 cups per day after controlling for confounders (P‐value of trend test: 0.14). The crude incidence rates were 6.8, 6.7 and 4.6%, respectively; the adjusted rates were 6.8, 6.7 and 4.0%, respectively. Coffee consumption was significantly (P<0.05) inversely correlated with serum selenium concentration (never previously described) and, positively or negatively, with a number of other potential risk factors: smoking, alcohol use, serum triglycerides, serum cholesterol, blood pressure, social class, body mass index, and serum selenium. In nonsmokers and smokers of only a small amount of tobacco, coffee consumption was associated with a lower risk of IHD (P<0.05).Conclusion. We conclude that the association between coffee consumption and risk of IHD is conditioned by known risk factors correlated with use of coffee, which may partly explain the inconsistencies in the results

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01140.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract.Objective. The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha‐1 (α‐1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin‐dependent diabetes mellitus patients with nephropathy.Design. The study consisted of a four‐week run‐in period, a four‐week active treatment period, a four‐week wash‐out period and a second four‐week active treatment period.Setting. The study was performed in the out‐patient clinic at a university hospital.Subjects. Ten patients with insulin dependent diabetes mellitus with macroalbuminuria (>200 μg min−1), mild to moderate hypertension (diastolic blood pressure 85–115 mmHg) and serum creatinine level below 200 μmol L−1were included in the study.Main outcome measures. The effect of the drugs on albumin and total protein excretion, β‐2‐microglobulin, proximal tubular enzyme markers and renal haemodynamics.Results. Systolic and diastolic blood pressure were equally reduced by both drugs. Enalapril reduced albumin excretion from 1090 ± 281 μg min−1to 742 ± 246 μg min−1(P<0.01) and total protein excretion from 2.0 ± 0.4 g per 24 h to 1.3 ± 0.4 per 24 h whereas doxazosin was without effect. Glomerular filtration rate and effective renal plasma flow were unchanged by either drug. Doxazosin increased filtration fraction from 0.21 ± 0.02 to 0.23 ± 0.01 (P<0.05). The urinary excretion of the proximal enzyme markers N‐acetyl‐beta‐glucosaminidase and alkaline phosphatase were elevated as well as urinary excretion of β‐2‐microglobulin. However, neither the excretion of β‐2‐microglobulin nor the enzyme markers were affected by either drug.Conclusions. Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy

ISSN:0954-6820    

DOI:10.1111/j.1365-2796.1995.tb01141.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY