bluuebunny/crossref_metadata_2025 huggingface dataset:
Progression of atherosclerosis in middle‐aged men: effects of multifactorial intervention
Authors: PERSSON JERKER , ISRAELSSON BO , STAVENOW LARS , HOLMSTRÖM EVA , BERGLUND GÖRAN
Published: November 2003

Persson J, Israelsson B, Stavenow L, Holmström E, Berglund G (Department of Medicine, Lund University Hospital, Malmö, Sweden). Progression of atherosclerosis in middle‐aged men: effects of multifactorial intervention. J Intern Med 1996; 239: 425–33.

Objective. To determine the effect of multifactorial intervention against cardiovascular risk factors on ultrasound‐determined progression of atherosclerosis in healthy middle‐aged men.

Design. One hundred and forty‐nine healthy middle‐aged men were assigned to an intervention group (IG) or a control group (CG).

Subjects. The participants had moderately increased risk‐factor scores for cardiovascular disease. They were recruited from a health screening programme at the Preventive Medicine Section, Department of Medicine, Lund University, University Hospital, Malmö. During the study period, 32 of the subjects were lost to follow‐up, leaving 59 in the IG and 58 in the CG.

Intervention. The IG subjects underwent multifactorial intervention for 2 years, the goal being to help them stop smoking and to reduce their blood lipids and blood pressure.

Main outcome measures. Intima–media thickness and plaque score in the right carotid artery were ultrasonographically determined initially and after 2 years. Blood lipids and blood pressure were measured at the same time, and in the IG also after 3, 6, 12 and 18 months after entry into the study.

Results. At the entry into the study, there were no significant differences in major risk factors or ultrasound variables between IG and CG. Blood lipids and smoking decreased significantly during the 2 years of intervention in the IG, whilst these factors remained unchanged in the CG. Intima–media thickness and plaque scores increased significantly in both groups.

Conclusions. No effects on ultrasound variables could be detected after 2 years of multifactorial intervention. A more aggressive intervention programme, possibly more dependent on pharmacological treatment, may be required to obtain reduced progression or regression of atherosclerosis.
Impaired suppression of plasma free fatty acids and triglycerides by acute hyperglycaemia‐induced hyperinsulinaemia and alterations in high density lipoproteins in essential hypertension
Authors: LIGTENBERG J. J. M. , A.  , VAN HAEFTEN T. W. , SLUITER W. J. , REITSMA W. D. , DULLAART R. P. F.
Published: November 2003

Objectives. Essential hypertension may be associated with abnormalities in free fatty acids (FFA) and triglyceride metabolism, which could lead to alterations in high density lipoproteins (HDL). Lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from HDL towards triglyceride‐rich lipoproteins. We compared baseline plasma lipids, HDL lipids, plasma LCAT and CETP activity as well as the lowering of plasma FFA and triglycerides by acute hyperglycaemia‐induced hyperinsulinaemia in patients with essential hypertension and control subjects.

Setting. University Hospital, Groningen.

Subjects and design. Eight patients with essential hypertension and eight control subjects were studied during a 3‐h hyperglycaemic glucose clamp (blood glucose, 10 mmol L‐1).

Main outcome measures. Plasma insulin, FFA, triglycerides and HDL lipids, plasma LCAT and CETP.

Results. Baseline plasma FFA, total cholesterol and HDL cholesterol were not different between the groups, but plasma triglycerides tended to be higher in the hypertensive patients (P<0.10). The baseline HDL free cholesterol content and the HDL free cholesterol/cholesteryl ester ratio were lower (P< 0.05 for both) in the hypertensive than in the control group. Although baseline plasma LCAT and CETP activity were not significantly different between the groups, the plasma LCAT/CETP ratio, reflecting the amount of active LCAT compared to that of CETP, was higher in the hypertensive patients (P<0.05). In the combined subjects and in the hypertensive group, the HDL free cholesterol content was negatively related to plasma triglycerides and to the LCAT/CETP ratio, whereas this ratio was positively correlated with plasma triglycerides (P0.01 for all correlations). During a 3‐h hyperglycaemic clamp (blood glucose 10 mmol L‐1) plasma FFA and triglycerides decreased to a lesser extent (P<0.02 and P=0.05) and remained higher (P<0.05 for both) in the hypertensive patients, despite similar plasma insulin levels.

Conclusion. The action of insulin on FFA metabolism is impaired which is likely to contribute to higher plasma triglycerides in essential hypertension. In turn, higher triglycerides influence the HDL lipid composition, either directly or via an effect on the plasma LCAT/CETP ratio.
Evolution of heart rate variability in cardiac transplant recipients: a clinical study
Authors: KOSKINEN PEKKA , VIROLAINEN JUHA , KOSKINEN PETRI K. , HÄYRY PEKKA , KUPARI MARKKU
Published: November 2003

Koskinen P, Virolainen J, Koskinen Pk, Häyry P, Kupari M (Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, and Transplantation Laboratory, University of Helsinki, Helsinki, Finland). Evolution of heart rate variability in cardiac transplant recipients: a clinical study. J Intern Med 1996; 239: 443–9.

Objectives. To investigate in cardiac transplant patients whether post‐transplantation time, graft arteriosclerosis, allograft rejection, or earlier cytomegalovirus infection affect the neural regulatory mechanisms of the donor heart.

Design. A consecutive series of heart transplant patients during a 12‐month period.

Setting. A university hospital in Finland.

Subjects. Consecutive cardiac transplant recipients (n=38) attending the hospital for their annual clinical examintaion were studied. Their mean (SD) age was 45.4 (11.5) years, 37 were male, and the median (range) time since transplantation was 36 (12–72) months.

Interventions. Power spectral analysis of R–R intervals (during 5 min of controlled breathing, the Valsalva manoeuvre, and deep breathing), routine coronary arteriography, cytomegalovirus serology.

Results. R–R interval (r=0.67; P<0.001), the root mean square difference of successive R–R intervals (r=0.38; P<0.05), the total R–R interval power (r=0.45; P<0.01), the power of the very low frequency (0.0–0.07 Hz) component (r=0.53; P<0.01), and the power of the nonrespiratory (0.0–0.15 Hz) component (r=0.49; P<0.01) were related to the length of time since the operation. Patients having had a transplantation 3 years ago or more had significantly greater median (range) total R–R interval power than those having had the operation less than 3 years ago (59 [10–265] vs. 20 [3–113] ms2; P=0.02). There was also a difference between the two groups in the very low frequency component (18 [1–226] vs. 5 [0–45] ms2; P=0.01), in the nonrespiratory component (30 [1–227] vs. 9 [0–53] ms2; P=0.02), and in the Valsalva ratio (0.995 [0.955–1.065] vs. 1.020 [0.975–1.155]; P=0.03). Patients with and without graft arteriosclerosis, episodes of rejection, or earlier cytomegalovirus infection showed no difference in the power spectral measures.

Conclusions. The donor heart rate variability increases with post‐transplantation time. Heart rate variability in transplant recipients is not related to the extent of graft arteriosclerosis, episodes of allograft rejection, or earlier cytomegalovirus infection.
Thyroid antibodies in northern Norway: prevalence, persistence and relevance
Authors: BRYHNI B. , AANDERUD S. , SUNDSFJORD J. , REKVIG O. P. , JORDE R.
Published: November 2003

Objectives. To investigate the prevalence and persistence of thyroid autoantibodies in a population sample and to assess the development of biochemical hypothyroidism (defined as an elevated serum thyrotropin [TSH] concentration) in relation to their presence.

Design and setting. A cross‐sectional and longitudinal study based on the Tromsø Study in 1979–80 and 1986–87.

Subjects and main outcome measures. From 2551 random participants in 1979–80 aged 34±8.4 (mean±SD) years, sera were available in 2513 and 2504 persons for determination by passive haemagglutination of the antibody to thyroid microsomal antigen (anti‐Tm) and of the antibody to thyroglobulin (anti‐Tg). Total thyroxine (TT4) and TSH were measured in 114 of 176 antibody‐positive subjects and in 101 controls. After 7 years, anti‐Tm and anti‐Tg were remeasured in 1939 and 1931 subjects, and TT4 and TSH in 92 of the initially antibody‐positive subjects and in 69 controls.

Results. Anti‐Tm occurred more frequently than anti‐Tg (in 6.1 vs. 2.8%; P<0.001). Anti‐Tm (P< 0.001) and anti‐Tg (P=0.027) were both more common in women than in men. The prevalence of anti‐Tm (P=0.025), but not of anti‐Tg, increased with age. Changes in titre levels after 7 years were mostly small or moderate. Both in women (P= 0.005) and in men (P<0.001) the TSH concentrations increased with increasing levels of anti‐Tm, whereas in men, the concentrations also increased with increasing anti‐Tg levels (P<0.001). Biochemical hypothyroidism developed with a 2.7% yearly incidence only in antibody‐positive subjects, all except one of whom had anti‐Tm.

Conclusions. The prevalences of thyroid antibodies were comparable to those found in similar studies in other areas. Their presence was associated with the development of biochemical hypothyroidism.
Changes in cardiovascular risk factors by combined pharmacological and nonpharmacological strategies: the main results of the CELL Study
Authors: LINDHOLM LARS H. , EKBOM TORD , DASH CLIVE , ISACSSON ÅKE , SCHERSTÉN BENGT
Published: November 2003

Objective. The objectives of the Cost Effectiveness of Lipid Lowering (CELL) study were twofold: (i) to evaluate the effect on overall cardiovascular risk of two types of health care advice (‘usual’ and ‘intensive’) given in primary care, with or without pharmacological medication, with the target being to attain a moderate decrease in cholesterol; (ii) to evaluate the ritual of daily medication on compliance with the health care advice.

Design. A prospective, double‐blind, randomized, controlled trial of 18 months' duration.

Setting. The study was carried out in 32 health centres (out of a total of approximately 850) in Sweden.

Subjects. In all, 681 subjects, aged 30–59 years, were randomized. They had at least two cardiovascular risk factors in addition to moderate primary hyperlipidaemia (total cholesterol of at least 6.50 mmol L‐1 on three occasions measured by Reflotron, triglycerides less than 4.0 mmol L‐1 and an LDL:HDL cholesterol ratio of more than 4.0). Most (87%) of the subjects were males; 626 subjects (92%) completed the 18‐month follow‐up.

Intervention: Half the subjects were randomized to ‘intensive advice’ given in group sessions led by doctors and nurses in primary care. The other half received ‘usual advice’. In each of the two advice groups, one‐third received an active lipid‐lowering drug (pravastatin), one‐third placebo, and one‐third no drug at all. The tablets were titrated to achieve a 15% reduction in cholesterol.

Main outcome measures. Changes in the overall Framingham risk score, and the development of adverse events in each group.

Results. The change in Framingham risk score was significantly reduced only in subjects taking lipid‐lowering medication (together with intensive advice‐0.13; 95% CI ‐0.20,‐0.06, and together with usual advice ‐0.16; 95% CI ‐0.23,‐0.09). The other subjects receiving intensive advice tended to fare better than those on usual advice. Lifestyle was not influenced significantly over the study period. The ritual of daily medication did not affect the outcome.

Conclusion. As expected, lipid‐lowering medication reduced serum cholesterol as well as overall cardiovascular risk in subjects with several risk factors for cardiovascular disease. There was no additive effect of intensive advice to these subjects. However, there was a meagre but significant effect of intensive advice in subjects not receiving active lipid‐lowering drugs. One explanation for this difference may be that those on active lipid‐lowering medication who had substantial drops in cholesterol might have felt less inclined to change their lifestyle compared with those on other treatment regimens who had less successful drops in cholesterol. There was no benefit from the ritual of taking daily medication.
Clinical features in persons with a family history of diabetes compared to controls (The Second Generation Fredericia Study)
Authors: VESTBO E. , DAMSGAARD E. M. , FRØLAND A. , MOGENSEN C. E.
Published: November 2003

Objective. To compare clinical and biochemical features in non‐diabetic persons with a family history of non‐insulin dependent diabetes mellitus (NIDDM) to non‐diabetic persons without a family history of diabetes.

Design. Cross‐sectional study.

Setting. Population‐based survey in Fredericia, Denmark.

Subjects. Seven hundred and forty subjects, the second generation of an earlier defined cohort was examined. The median age was 48 (range 26–65) years. Of the 740 subjects 696 were non‐diabetic.

Interventions. The subjects had a clinical examination.

Main outcome measures. Known risk factors for development of diabetes and cardiovascular disease.

Results. More offspring of diabetic persons had NIDDM (χ2=6.36, P<0.05). Non‐diabetic males with a family history of diabetes had a higher BMI, fasting blood glucose, and triglycerides compared to males without a family history of diabetes. Non‐diabetic females with a family history of diabetes had a higher BMI, fasting blood glucose, HbA1C, diastolic blood pressure, and lower HDL‐cholesterol than female offspring of non‐diabetics. In a multiple regression model we found that non‐diabetic offspring of diabetic persons had higher fasting blood glucose and HbA1C compared to offspring of non‐diabetic persons when adjusted for the independent variables age, BMI, WHR, and sex.

Conclusion. Our results may indicate that the only inherited factors from NIDDM patients are plasma blood glucose, HbA1C and increased BMI which may be an indication for later diabetes, whereas other cardiovascular risk factors may be inherited independently of diabetes but associated with BMI.
Two variants of extracellular‐superoxide dismutase: relationship to cardiovascular risk factors in an unselected middle‐aged population
Authors: Marklund S. L. , Nilsson P. , Israelsson K. , Schampi I. , Peltonen M. , Asplund K.
Published: November 2003

Marklund SL, Nilsson P, Israelsson K, Schampi I, Peltonen M, Asplund K (University Hospital, Umeå, Sweden). Two variants of extracellular‐superoxide dismutase: relationship to cardiovascular risk factors in an unselected middle‐aged population. J Intern Med 1997; 242: 5–14.

Objective

Description of the distribution of plasma levels of two variants of extracellular‐superoxide dismutase (EC‐SOD) and their relationship to cardiovascular risk factors in the general population.

Design

A cross‐sectional study.

Setting

Norrbotten and Västerbotten counties in northern Sweden.

Subjects

Four thousand, nine hundred 25–74‐year‐old randomly selected subjects.

Main outcome measures

Plasma levels of EC‐SOD. Genotyping by an allele‐specific PCR method.

Results

Plasma EC‐SOD levels showed a distinct bimodal distribution with the smaller group (3.8%) having a variant of the enzyme with about eight‐fold‐higher plasma levels. Genotyping was performed in 65 individuals with the high‐level variant. All but one were found to carry the same mutation, Arg213Gly, affecting the heparin‐binding domain of EC‐SOD. Subjects with the high‐level variant of EC‐SOD had modestly higher body mass index and higher levels of serum cholesterol, serum triglycerides and plasma fibrinogen than those with the common EC‐SOD phenotype. Within the population with common EC‐SOD, the plasma levels were lower in men than in women and increased with age. Low levels of common phenotype EC‐SOD were associated with smoking, high plasma levels of fibrinogen and low activity of tissue plasminogen activator in both univariate and multivariate analyses. Obesity and total serum cholesterol were associated with high common phenotype EC‐SOD levels.

Conclusions

A high‐level variant of EC‐SOD caused by one and the same mutation and with low tissue binding and high plasma levels is present in approximately four per cent of an unselected middle‐aged population in northern Sweden. Plasma levels of EC‐SOD may be modulated by lifestyle factors such as smoking and show a complex covariation with many of the conventional cardiovascular risk factors.
Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation
Authors: Gerdin B. , Hällgren R.
Published: November 2003

Gerdin B, Hällgren R (University Hospital, Uppsala, Sweden). Dynamic role of hyaluronan (HYA) in connective tissue activation and inflammation (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 49–55.

An increased tissue accumulation of HYA occurs in several human and experimental inflammatory conditions. Such is the case in sarcoidosis, idiopathic pulmonary fibrosis and farmer's lung in man, and experimental bleomycin‐induced lung damage in rats. Graft rejection in man and rats, experimental myocarditis in mice and myocardial infarction in rats follow the same pattern. Increased amounts of HYA also appear in gut luminal perfusion fluid in human inflammatory bowel disease. A transient accumulation of HYA is seen in wound healing, which is more sustained in fetuses. An increased accumulation of water and presentation of ligands for receptors on inflammatory cells are two consequences of the HYA accumulation.
Hyaluronan in skin
Authors: Juhlin L.
Published: November 2003

Juhlin L (University Hospital, Uppsala, Sweden). Hyaluronan in skin (Minisymposium: Hyaluronan) J Intern Med 1997; 242: 61–6.

Because of the abundance of hyaluronan in skin, interest was early focused on variation in the content of the polysaccharide in various pathological conditions of this tissue. A large amount of early work utilized histological techniques of insufficient specificity but recent developments of specific analytical and staining methods for hyaluronan have supplied new data on its presence and possible role in skin disorders.
Cognitive function, vascular risk factors and education. A cross‐sectional study based on a cohort of 70‐year‐old men
Authors: Kilander L. , Nyman H. , Boberg M. , Lithell H.
Published: November 2003

Kilander L, Nyman H, Boberg M, Lithell H (Uppsala University Hospital, Uppsala; and the Karolinska Institute, Stockholm; Sweden). Cognitive function, vascular risk factors and education. A cross‐sectional study based on a cohort of 70‐year‐old men. J Intern Med 1997; 242: 313–21.

Objectives

A low level of education is associated with an increased risk of developing a dementia disorder, as well as with a higher risk of cardiovascular disease. The aim of this study was to investigate the association between education and cardiovascular risk factors, and to study the relation between these factors and cognitive function in elderly men.

Design

Cross‐sectional population‐based study.

Setting

Uppsala, Sweden.

Subjects

504 men aged 69–74 years, participants in a longitudinal health survey concerning cardiovascular risk factors.

Main outcome measure

Cognitive function as measured by a composite score of 13 standard psychometric tests.

Results

A low level of education was associated with poorer cognitive performance, as well as with obesity, smoking, diabetes, high concentrations of serum triglycerides and plasma fibrinogen. In the entire cohort, subjects with obesity, smoking, diabetes or hypertriglyceridaemia showed impaired cognitive test results, independent of socio‐economic factors. When stroke cases were excluded, obesity and smoking were still related to impaired cognitive function.

Conclusions

Smoking and obesity with associated metabolic disturbances are inversely related both to educational level and to cognitive function. Cognitive decline of vascular origin is potentially preventable by treatment of risk factors. The question of whether the increased vascular risk contributes to the higher prevalence of cognitive disorders in individuals with low socio‐economic status, needs to be further evaluated in longitudinal population‐based studies.
Proinflammatory cytokines, measured in a mixed population on arrival in the emergency department, are related to mortality and severity of disease
Authors: CARLSTEDT F. , LIND L. , LINDAHL B.
Published: November 2003

Carlstedt F, Lind L, Lindahl B (University Hospital of Uppsala, Sweden). Proinflammatory cytokines, measured in a mixed population on arrival in the emergency department, are related to mortality and severity of disease. J Intern Med 1997; 242: 361–5.

Objectives

To investigate whether serum levels of tumour necrosis factor alpha (TNF‐α) and interleukin 6 (IL‐6) are related to mortality and severity of disease in patients admitted to the Emergency Department (ED).

Design

Prospective cohort study.

Setting

Emergency Department of a tertiary university hospital.

Subjects

A total of 140 patients admitted to the ED, representing common acute medical diseases, such as stroke, obstructive lung disease, heart failure, myocardial infarction, angina pectoris, infectious diseases and acute abdominal disorders.

Main outcome measures

APACHE II score at admission, hospital mortality and length of stay in hospital (LOS).

Results

A moderate rise in cytokine levels (IL‐6; 50–300 ng L−1, TNF‐α; 10–70 ng L−1) was found in all diagnosis‐groups, with the most pronounced elevation seen in patients with acute abdominal disorders (up to 6900 ng L−1). IL‐6 on arrival to the ED was significantly correlated to the APACHE II score (r= 0.48, P < 0.0001), LOS (r= 0.36, P < 0.0001) and was elevated in nonsurvivors (n=9) compared to those who did survive. TNF‐α on arrival showed a significant correlation to LOS (r= 0.36, P < 0.0001) and APACHE II (r= 0.41, P < 0.0001), but was not associated to later mortality.

Conclusions

Serum levels of proinflammatory cytokines collected at admission to the ED were related to the severity of disease and hospital mortality.
The anti‐oestrogen tamoxifen produces haemodilution in normal postmenopausal women
Authors: Grey A. B. , Evans M. C. , Kyle C. , Reid I. R.
Published: November 2003

Grey AB, Evans MC, Kyle C, Reid, IR (University of Auckland, Auckland, New Zealand). The anti‐oestrogen tamoxifen produces haemodilution in normal postmenopausal women. J Intern Med 1997; 242: 383–8.

Objectives

To report the effects of the anti‐oestrogen tamoxifen on biochemical and haematological parameters.

Design

Randomized, double‐blind comparison of tamoxifen 20 mg per day and placebo, over two years.

Setting

A university hospital.

Subjects

Forty‐six healthy late‐postmenopausal women (mean, SD time since menopause; 11, seven years).

Main outcome measures

Blood specimens were drawn in the fasting state at baseline, six months and two years for measurement of haemoglobin, haematocrit, erythrocyte mean cell volume, mean erythrocyte haemoglobin, leucocyte count, platelet count, urea, electrolytes, creatinine and albumin.

Results

There was a significant decline in the haemoglobin concentration in the tamoxifen group (−4.4, 1.2 g/L; mean, SE) and its levels were lower in this group than in those receiving placebo (P= 0.004). Similarly, haematocrit, erythrocyte count and total leucocyte count were lower in those on placebo (P= 0.002, P= 0.01 and P= 0.01, respectively) and platelet count showed a similar trend (P= 0.08). In the tamoxifen group, the level of serum albumin fell significantly (−2.2, 0.4 g/L) and was lower throughout the study than that in the placebo group (P= 0.006). That of serum urea tended to fall (−0.4, 0.2 mmol L) but the between‐groups comparison was not significant (P= 0.18).

Conclusions

These data suggest that tamoxifen exerts a haemodilutory effect in normal postmenopausal women. Since a similar effect has been reported in response to postmenopausal oestrogen therapy, it is likely that the observed changes represent another oestrogenic effect of tamoxifen in postmenopausal women. Haemodilution may contribute to the reduced incidence of cardiovascular disease reported in tamoxifen‐treated women, and, therefore, its assessment in the new oestrogen agonists/antagonists being developed for cardiovascular disease prevention may be important.
Narrow hips and broad waist circumferences independently contribute to increased risk of non‐insulin‐dependent diabetes mellitus
Authors: Seidell J. C. , Han T. S. , Feskens E. J. M. , Lean M. E. J.
Published: November 2003

Seidell JC, Han TS, Feskens EJM, Lean MEJ (National Institute of Public Health and the Environment, Bilthoven, the Netherlands, and Royal Infirmary, University of Glasgow, Glasgow, UK). Narrow hips and broad waist circumferences independently contribute to increased risk of non‐insulin‐dependent diabetes mellitus. J Intern Med 1997; 242: 401–406.

Objectives

Patients with non‐insulin‐dependent diabetes mellitus (NIDDM) have been shown to be more obese and have higher waist‐to‐hips circumference ratios compared to nondiabetics. In this study, we tried to dissociate obesity, waist and hip circumference from NIDDM.

Design

A cross‐sectional population‐based case‐control study.

Setting

General population.

Subjects

Controls: 5887 men and 7018 women, aged 20–59 years, without known diabetes or hyperglycaemia. Cases: 93 men and 66 women were diagnosed with NIDDM.

Main outcome measures

We predicted waist and hips' circumference from the body mass index, weight/height2, (BMI) on the basis of linear regression. Differences between observed and expected values (residuals) of waist and hip circumference were categorized into tertiles. The relative odds of having NIDDM in tertiles of waist and hip residuals (middle tertile as reference) were calculated by multiple logistic regression analysis adjusted for each other and for age, smoking, physical activity, alcohol consumption and education.

Results

NIDDM was most prevalent in men and women who had larger waists and in those who had smaller hip circumferences than expected from their BMI. Adjusted odds ratios (95% CI) for NIDDM were 2.9 (1.6–5.1) in men and 2.8 (1.5–5.1) in women who had a larger than expected waist, and were 3.7 (2.1–6.5) in men and 2.1 (1.1–3.8) in women who had smaller than expected hips.

Conclusions

Our findings suggest that diabetics have larger waists and smaller hips compared to nondiabetics, irrespective of their degree of obesity, age and life‐style factors. One possibility is that besides abdominal fatness, peripheral muscle atrophy is one of the factors associated with NIDDM.
Medical risk factors amongst drivers in single‐car accidents
Authors: GISLASON T. , TÓMASSON K. , REYNISDÓTTIR H. , BJÖRNSSON J. K. , KRISTBJARNARSON H.
Published: November 2003

Objectives. To estimate medical risk factors amongst drivers in single‐car accidents with special reference to sleepiness and alcohol abuse.

Design. An epidemiological survey by means of multiple‐choice questionnaires that were mailed to drivers and a random control group.

Setting. Iceland.

Subjects. All drivers in single‐car accidents (n=471) during 1989–91 and a control group from the general population (n=1000).

Main outcome measure. Medical health profile and answers to questions concerning sleep disorders and alcohol abuse.

Results. Compared to the controls the drivers were younger and there were three times more males. The drivers abused alcohol more often. Chronic disorders such as epilepsy, diabetes mellitus, and cardiac disorders were not over‐represented. Altogether, 15.4% claimed that sleepiness had caused their traffic accident, logistic regression analyses revealed that these ‘sleepy’ drivers more often had alcohol abuse and a history of ‘almost falling a sleep whilst driving’.

Conclusions. Compared to controls, drivers in single‐car accidents are more likely to be young, male, have a history of sleepiness whilst driving, and also have a history suggestive of alcoholism. Chronic disorders like epilepsy and diabetes mellitus were not over‐represented amongst the single‐car accidents drivers. These results raise the question of how drivers with a high probability of causing an accident (sleepiness and alcoholism) can be identified in time and proper measures taken to prevent ‘accidents waiting to happen’.
Congestive heart failure in old age: prevalence, mechanisms and 4‐year prognosis in the Helsinki Ageing Study
Authors: KUPARI M. , LINDROOS M. , IIVANAINEN A. M. , HEIKKILÄ J. , TILVIS R.
Published: November 2003

Objective. To examine the prevalence, underlying diseases, abnormalities of left ventricular function and prognosis in congestive heart failure (CHF) of old age.

Design. A population‐based clinical and echocardiographic study with a 4‐year mortality follow‐up.

Setting. University hospital.

Subjects. Five hundred and one individuals born in 1904, 1909 and 1914 (367 women).

Main outcome measures. Presence of CHF by clinical and chest radiograph criteria; left ventricular size and systolic function by echocardiography; grade of aortic and mitral valve lesions by Doppler echocardiography; 4‐year total and cardiovascular mortality.

Results. Forty‐one of 501 participants (8.2%) had CHF. Ischaemic heart disease (54%), hypertension (54%) and moderate‐to‐severe mitral or aortic valve disease (51%) were the main underlying conditions; 90% of patients had one or more of these diseases. Most individuals with CHF (28 of 39 patients, 72%) had normal left ventricular contractions at echocardiography. ‘Diastolic CHF’, defined as CHF with normal systolic left ventricular function and no regurgitant valve disease, was found in 51% (20 of 39 patients). The relative 4‐year risk for death associated with CHF, adjusted for age and sex, was 2.1 (95% confidence interval 1.3–3.4) for all‐cause mortality and 4.2 (CI 1.9–5.6) for cardiovascular mortality.

Conclusions. The prevalence of CHF in a population aged 75–86 years is approximately 8%. Ischaemic or valvular heart disease and hypertension are the main underlying conditions. At echocardiography, about 50% of the elderly with CHF have normal left ventricular systolic contractions in the absence of valve disease and an additional 20% have normal systolic function with mitral regurgitation. The presence of CHF doubles the age‐ and sex‐adjusted risk of death from all causes, and quadruples the risk of cardiovascular death during 4‐year follow‐up.
Predictors of weight loss during treatment with d‐fenfluramine
Authors: TOORNVLIET A. C. , PIJL H. , HOPMAN E. , WESTENDORP R. G. J. , MEINDERS A. E.
Published: November 2003

Objectives. To identify parameters predictive of weight loss during treatment with d‐fenfluramine. This may provide a tool to recognize patients who are sensitive to the weight‐reducing effect of d‐fenfluramine and thus prevent unnecessary prescription.

Design. An open intervention study during which biweekly control visits were scheduled. The study lasted 12 weeks.

Setting. The General Internal Medicine outpatient clinic of the Leiden University Hospital. Patients were recruited through a newspaper advertisement.

Subjects. Forty‐eight healthy, obese patients (36 women and 12 men), aged 39±10 years (mean±SD) with a body mass index of 34.3±4.1 kg/m2 enrolled.

Interventions.
d‐Fenfluramine 15 mg twice daily for 12 weeks.

Main outcome measures. Body weight, height, waist and hip circumference, food intake, smoking habits, obesity history, treatment history, family history of obesity and compliance with the medication scheme were recorded as potential predictors of weight loss.

Results. One patient was withdrawn because of depressive symptoms. Thirteen patients did not lose weight. On average, the other 34 patients lost 5.7±2.9 kg or 18.1±9.4% of excess body weight. High compliance with the drug regimen was associated with a twofold greater weight loss (17.7±12.3 vs. 9.0±9.4% of excess weight, ANOVAP=0.0088). Patients with a positive family history of obesity lost twice as much weight as patients without obese relatives (15.8±11.8 vs. 6.0±7.3% of excess weight; ANOVA, P=0.0078). No other potential determinants were predictive for weight loss.

Conclusions. Informing patients that compliance with the medication scheme improves treatment outcome will be useful. Previous failures to lose weight should not exclude patients from treatment. A positive family history of obesity needs further evaluation as a possible determinant of weight loss in forthcoming studies.
Do‐not‐resuscitate orders – should the patient be informed?
Authors: LÖFMARK R. , NILSTUN T.
Published: November 2003

Objectives. To analyse the ethical implications of informing patients about their do‐not‐resuscitate status (DNR).

Design. Questionnaire.

Setting. Nationwide, 6 months after the publication of guidelines on DNR in 1994.

Subjects. A 10% random sample of the members of the Swedish Cardiac Society, 104 physicians and 196 nurses.

Main outcome measures. To what extent are patients, physicians and nurses involved in decisions about DNR, and how should the ethical conflict involved in informing patients about their DNR status be described and analysed?

Results. Of 73% responding, 84% of the physicians and 8% of the nurses had made a DNR decision. The decision was regarded as ethically right and well timed and it was discussed with 33% of the competent patients. Half of the respondents believed that DNR orders should be discussed with the competent patient, but still only one third of the patients are involved. The ethical conflict is analysed using the principles of autonomy and nonmaleficence as value premises.

Conclusions. Many physicians are still reluctant to find out what the patient wants. Being ignorant they risk harming the patient. It is recommended that information about DNR status should be given incrementally and that the attitudes of the old and chronically ill in‐hospital patients are studied. Do they want to be informed, and if so, how and when do they want it to be done?
Glucose and insulin levels in young subjects with different maternal histories of hypertension: The Hypertension in Pregnancy Offspring Study
Authors: HIMMELMANN A. , HIMMELMANN K. , SVENSSON A. , HANSSON L.
Published: November 2003

Objective: To analyse whether hypertension during pregnancy is associated with early signs of impaired glucose metabolism in the offspring.

Design: Longitudinal study with a 5‐year follow‐up.

Setting: University Hospital, Göteborg, Sweden.

Main outcome measures: Fasting levels of glucose, insulin and C‐peptide.

Subjects: Thirty‐six children were born to mothers with hypertension in pregnancy. The children were divided into two groups according to their mothers' blood pressure at follow‐up 7–12 years after pregnancy. Nineteen children had hypertensive mothers (HT), while 17 children had normotensive mothers at follow‐up (NT). A control group (C) comprised 16 children, who were born after normotensive pregnancies to mothers who remained normotensive.

Results: Fasting plasma glucose was significantly higher in HT than in NT (5.2 vs. 4.9 mmol L−1; P < 0.05). In C fasting glucose was 5.1 mmol L−1. The same trend was seen for fasting insulin in HT, NT and C, respectively (6.7 vs. 4.7 vs. 5.3 μU mL−1). The C‐peptide level was 1.61, 155 and 1.64 ng mL−1, respectively. Calculated insulin resistance was 1.5 in HT, 1.0 in NT and 1.2 in C.

Conclusions: It is suggested that hypertension during pregnancy may be associated with impaired glucose metabolism and elevated fasting glucose levels in the offspring during adolescence.
The concentration of sodium,potassium pumps in chronic obstructive lung disease (COLD) patients: the impact of magnesium depletion and steroid treatment
Authors: RAVN H. B. , DØRUP I.
Published: November 2003

Objectives. To evaluate the concentrations of magnesium (Mg), potassium (K) and sodium,potassium pumps (Na,K pumps) in skeletal muscle in patients with chronic obstructive lung disease (COLD) treated with or without diuretics.

Design. An open cross‐sectional study.

Setting. COLD patients admitted to the Medical Department of Vejle Hospital, Denmark.

Subjects. Thirty‐six consecutive COLD patients and 23 age‐ and sex‐matched controls.

Main outcome measures. Biopsies of skeletal muscle were performed in patients and controls for measurements of Mg, K and Na,K pumps. In a parallel animal experiment the influence of medical treatment on the concentration of Na,K pumps in skeletal muscle was evaluated by infusing 10‐week‐old rats for 14 days with vehicle, terbutaline, or dexamethasone.

Results.In the patients, mean muscle Mg and K concentrations were reduced by 22 and 14%, respectively (P<0.001), but in those patients who received diuretics muscle Mg and K were further reduced (by 31 and 27%, respectively, of the control values). The concentration of Na,K pumps was increased by 31% (P < 0.001), with a maximum increase of 61% (P lt;−0.001) in 12 intensive care patients receiving high dosages of glucocorticoids. Linear regression analysis showed a positive correlation between daily glucocorticoid intake and the concentration of Na,K pumps in the biopsy specimens from each patient (r = 0.38, P = 0.02). In the experimental study, dexamethasone induced 27–34% increase in the concentration of Na,K pumps (P < 0.01) in three different muscles, whereas there was no significant change following terbutaline infusion.

Conclusions. COLD patients show reduced concentrations of Mg and K in skeletal muscle, associated with an upregulation of the Na,K pump concentration. It is plausible that this upregulation may be caused by glucocorticoid treatment. The clinical benefits of glucocorticoids may in part be due to an increase in the activity and capacity of the Na, K pump and thereby in a possible enhancement of muscle force.
Pitfalls in the diagnosis of hypereosinophilic syndrome: a report of two cases
Authors: DE VRIESE A. S. , KIPS J. C. , VOGELAERS D. P. , VANDEWOUDE K. H. , CUVELIER C. A. , COLARDYN F. A.
Published: November 2003

The idiopathic hypereosinophilic syndrome is empirically defined as the presence of prolonged eosinophilia without identifiable underlying cause, and with evidence of end‐organ dysfunction. Virtually any organ system may be involved, most frequently the heart, the central and peripheral nervous system, the lungs and the skin. We report two cases where the diagnosis of hypereosinophilic syndrome was proposed although the classic criteria were not met. In the first case total peripheral eosinophil counts were relatively low, but pathological evidence clearly showed infiltration of eosinophils in the damaged tissues. An hypothesis to explain this discrepancy is formulated. The second case did not fulfil the first feature either, although the clinical presentation and disease course corresponded well with other cases reported in the literature. The delay in diagnosis was caused by early institution of corticosteroids, clearing all evidence of eosinophil involvement in the observed tissue damage.
Type I hereditary angio‐oedema. Variability of clinical presentation and course within two large kindreds
Authors: WINNEWISSER J. , ROSSI M. , SPÄTH P. , BÜRGI H.
Published: November 2003

Objectives. Hereditary angiooedema (C1‐inhibitor deficiency) is a disease with protean manifestations which is often misdiagnosed initially. The purpose of this study was to delineate the clinical spectrum and course of this potentially life‐threatening disease.

Setting. Ten members of two unrelated affected kindreds were repeatedly hospitalized in our service with attacks of angiooedema. Among the 271 members of the two kindreds 69 were identified who reported typical attacks.

Design and subjects. Detailed information on the clinical course and laboratory data (C1‐inhibitor concentration and activity, C4 concentration) were obtained from 59 of the 69 affected subjects.

Results. C1‐inhibitor concentration and activity were low in all affected patients. The disease had become manifest by age 30 years in 98%. Most patients suffered from attacks of subcutaneous swellings and abdominal pain, and half of the patients have had attacks affecting the airways. The frequency of attacks ranged from less than one to over 26 per year. Forty‐two per cent had to be hospitalized at least once. Four have died of acute airway obstruction. Thirty‐eight attacks in 10 patients hospitalized in our service were all treated successfully with fresh frozen plasma or with C1‐inhibitor concentrate. Trauma, stress, insect stings and foodstuff were triggering factors, but the majority of attacks occurred without an identifiable trigger. Oral contraceptives and pregnancy led to worsening of symptoms. Nonetheless, all 36 pregnancies reported were carried to term. Twenty‐five patients were on continuous treatment with attenuated androgens or tranexamic acid, but only seven were free of attacks in the year preceding the survey.

Conclusion. Hereditary angiooedema is an autosomal dominant disease with great variability of clinical expression and severity, even within a single kindred. It often goes unrecognized over years, and it may lead to death if, in case of impending airway obstruction, specific therapy is not instituted.
Molecular genetics of familial hypercholesterolaemia in Norway
Authors: LEREN T. P. , TONSTAD S. , GUNDERSEN K. E. , BAKKEN K. S. , RØDNINGEN O. K. , SUNDVOLD H. , OSE L. , BERG K.
Published: November 2003

Objectives. To characterize mutations in the low density lipoprotein (LDL) receptor gene causing familial hypercholesterolaemia (FH) amongst Norwegian patients.

Design. Molecular genetic analyses of the LDL receptor gene have been performed in patients with a clinical diagnosis of FH.

Subjects. A total of 742 probands have been studied. Of these, 476 had a diagnosis of definite FH. The rest had a diagnosis of possible FH.

Results. Twenty‐three different mutations in the LDL receptor gene as well as the apolipoprotein B‐3500 mutation have been found. Six of the mutations in the LDL receptor gene are novel mutations. A molecular genetic diagnosis was achieved in 295 of the probands with definite FH (62%) and in 317 probands total. Of the 317 probands, 3% carried the apolipoprotein B‐3500 mutation. When family members were included, a total of 624 persons carried a mutation in the LDL receptor gene and 20 carried the apolipoprotein B‐3500 mutation.

Conclusions. Approximately 5% of Norwegian FH patients have been provided with a molecular genetic diagnosis. Our data suggest that molecular diagnosis of FH in Norway is feasible and should be implemented in clinical medicine.
First clinical experiences with specific sheep Fab fragments in snake bite. Report of a multicentre study of Vipera berus envenoming
Authors: KARLSON‐STIBER C. , PERSSON H. , HEATH A. , SMITH D. , AL‐ABDULLA I. H. , SJÖSTRÖM L.
Published: November 2003

Objectives. To evaluate the efficacy and safety of specific, ovine Fab fragments in the treatment of envenoming by the common adder, Vipera berus.

Design. Open study with historical controls.

Setting. Multicentre study involving patients (n = 30) with V. berus envenoming, treated in 18 Swedish hospitals during 1991–94.

Main outcome measures. Initial symptoms, clinical course after treatment, duration of hospital stay and adverse effects of the antivenom were evaluated. Two earlier studied patient groups, given either equine F(ab′)2 antivenom (n = 30) or no antivenom (n = 16), were used as controls.

Results. Specific ovine Fab fragments influenced favourably the acute symptomatology as well as the long term clinical course. Acute symptoms such as hypotension, shock, vomiting, diarrhoea and CNS‐depression resolved quickly. The incidence of extensive swelling involving the trunk and the length of hospital stay were both reduced significantly compared to nontreated patients (23 vs. 88% and 3.5 vs. 6 days). Also the incidence of anaemia was reduced (23 vs. 44%). These results were consistent with those obtained with equine F(ab′)2 antivenom, but with ovine Fab there were no immediate anaphylactic reactions or serum sickness.

Conclusion. Specific Fab fragments produced from sheep immunized with V. berus venom were safe and effective in counteracting the effects of V. berus bite in humans. These results justify further studies of this new treatment for snake envenoming.
Cardiovascular risk factors and electrographical characteristics and abnormalities in middle‐aged males
Authors: LIND L. , SUNDSTRÖM J. , LITHELL H.
Published: November 2003

Objectives. To evaluate if characteristics and abnormalities found at the electrocardiogram (ECG) are related to common cardiovascular risk factors included in the insulin‐resistance metabolic syndrome.

Design. Cross‐sectional.

Setting. Tertiary university hospital.

Subjects. Over 2000 middle‐aged males in whom ECG abnormalities were recorded, together with ECG characteristics measured in a random sample of men with no ECG abnormalities (n=113).

Interventions. None.

Results. All three components of the metabolic syndrome; elevated blood pressure, dyslipidaemia and hyperinsulinaemia were found to be related to the heart rate (P<0.002) and the QRS‐duration (P<0.01) and inversely to the QoT‐interval (P<0.05), the early diastolic phase (P<0.05) and the T‐wave amplitude (P<0.02). The components of the metabolic syndrome was furthermore found to be associated with the occurrence of T‐wave abnormalities (n=64, P<0.01) and to a lesser degree also to the occurrence of Q‐waves (n=21).

Conclusions. The components of the insulin‐resistance metabolic syndrome were related both to certain ECG characteristics in subjects with a normal ECG and to some ECG abnormalities. A raised sympathetic activity is likely to be the link between some of the described associations, whilst coronary heart diseases may explain others.
Influence of menopause on blood cholesterol levels in women: the role of body composition, fat distribution and hormonal milieu
Authors: PASQUALI R. , CASIMIRRI F. , PASCAL G. , TORTELLI O. , MORSELLI LABATE A. M. , BERTAZZO D. , VICENNATI V. , GADDI A. , Virgilio Menopause Health Group
Published: November 2003

Objectives. In this study we investigated the relationships between blood lipids and menopausal status.

Setting and subjects. All data were obtained from the first cross‐sectional examination of the Virgilio Menopause Health Project in a large cohort of middle‐aged women in pre, peri‐, and postmenopausal age. The data refer to 426 women without metabolic or endocrine diseases, relevant hepatic, renal and cardiovascular abnormalities, none were dieting or taking medications.

Main outcome measures. A precoded questionnaire including full clinical history, socio‐economic and personal information, habitual diet, physical activity, drug use and smoking habits, careful recording of gynaecological events and family history for disease was completed. Several anthropometric parameters and the bioelectrical impedance analysis was used to measure free fatty mass. Blood samples for hormones and biochemistry were also obtained.

Results. There were no significant differences on body mass index, fatty mass, free fatty mass and parameters of body fat distribution between the three groups. Again, there were no differences in smoking habits, dietary intake or indices of physical activity amongst the groups. There was a significant increase from pre to postmenopause of LH and FSH and a decrease of oestradiol and testosterone, whereas no difference was found in sex hormone‐binding globulin. Age‐adjusted values of glucose, triglycerides and high density lipoprotein (HDL‐) cholesterol were similar in all groups, whereas postmenopausal women had significantly higher values of total and low density lipoprotein (LDL‐) cholesterol. On the contrary, there was a significant fall in insulin levels passing from pre to postmenopause. In multiple regression models, total and LDL‐cholesterol correlated positively with body mass index, waist‐to‐hip ratio and age, and negatively with free fatty mass and oestradiol blood levels.

Conclusions. These results are consistent with the hypothesis that menopausal status may have a significant and independent effect in determining increased total and LDL‐cholesterol concentrations in postmenopausal women.