bluuebunny/crossref_metadata_2025 huggingface dataset:
Nephropathy in type 2 diabetes
Authors: Ritz E.
Published: March 2003

End‐stage renal failure (ESRF) in diabetic patients, mostly type 2, has become the most frequent cause of renal replacement therapy in western Europe. The majority of patients with type 2 diabetes and renal failure suffer from diabetic glomerulosclerosis, but non‐diabetic renal disease and atypical presentations, e.g. as irreversible acute renal failure or ischaemic nephropathy, play an increasingly important role. Known risk factors for the onset of diabetic nephropathy include (1) genetic predisposition (indicated by a history of hypertension and cardiovascular events in first‐degree relatives), (2) quality of glycaemic control, (3) level of blood pressure, and (4) smoking. At the time when type 2 diabetes is diagnosed, an abnormal blood pressure profile is found in approximately 80%. In patients with established diabetic nephropathy, hypertension is the most important factor which promotes progression, and this is susceptible to intervention. Although less data are available for type 2 diabetes (compared with type 1 diabetes), ACE inhibitors appear to be the antihypertensive agent of first choice, but monotherapy is rarely sufficient to achieve the blood pressure goal. Although, at least in principle, diabetic nephropathy is a preventable condition, currently only a minority of type 2 diabetic patients in western Europe receives adequate medical treatment to prevent onset or progression of diabetic nephropathy. Consequently, novel approaches to patient management and interdisciplinary interaction are necessary to fulfil the postulate of the St Vincent declaration concerning prevention of diabetic complications.
Aetiology and clinical significance of thrombocytosis: analysis of 732 patients with an elevated platelet count
Authors: Griesshammer M. , Bangerter M. , Sauer T. , Wennauer R. , Bergmann L. , Heimpel H.
Published: March 2003

Objective.  To determine the aetiology and clinical significance of an elevated platelet count (thrombocytosis) in a large cohort of patients.

Design.  A retrospective review of the medical records was performed on all patients, who had at least one platelet count ≥ 500 × 109 L–1.

Setting.  Departments of Medicine and Surgery, University of Ulm, Germany.

Subjects.  A total of 732 patients with thrombocytosis.

Main outcome measures.  Classification of thrombocytosis and thromboembolic complications, and evaluation of laboratory parameters distinguishing between primary and secondary thrombocytosis.

Results.  Of the total of 732 patients, 89 (12.3%) had primary and 643 (87.7%) had secondary thrombocytosis. Essential thrombocythaemia was observed in 40 of 89 patients (45%) with primary thrombocytosis. The most frequent causes of secondary thrombocytosis were tissue damage (42%), infection (24%), malignancy (13%) and chronic inflammation (10%). Primary thrombocytosis was significantly associated with a higher platelet count and an increased incidence of both arterial and venous thromboembolic complications. In secondary thrombocytosis, thromboembolic events were restricted to the venous system and occurred only in the presence of other risk factors. Mean values of leucocyte count, haematocrit, erythrocyte sedimentation rate, fibrinogen, serum potassium and lactate dehydrogenase were significantly different in primary and secondary thrombocytosis.

Conclusions.  The finding of an elevated platelet count on routine blood examination has diagnostic, prognostic and therapeutic implications. It is of clinical importance to distinguish between primary and secondary thrombocytosis, as thrombotic complications occur more frequently in primary thrombocytosis. Unless additional risk factors are present, secondary thrombocytosis is not associated with a significant risk for thromboembolic events.
The circulating renin–angiotensin system during treatment with metoprolol or captopril in patients with heart failure due to non‐ischaemic dilated cardiomyopathy
Authors: Jansson K. , Dahlström U. , Karlberg B. E. , Karlsson E. , Nylander E. , Nyquist O. , Karlberg K.‐E.
Published: March 2003

Abstract.  Jansson K, Dahlström U, Karlberg BE, Karlsson E, Nylander E, Nyquist O, Karlberg K‐E (Linköping University Hospital and Huddinge University Hospital, Sweden). The circulating renin–angiotensin system during treatment with metoprolol or captopril in patients with heart failure due to non‐ischaemic dilated cardiomyopathy. J Intern Med 1999; 245: 435–443.

Objective.  To investigate the effects of beta‐blocker (metoprolol) or angiotensin‐converting enzyme inhibitor (captopril) treatment on neurohormonal function in a randomized prospective study on patients with heart failure due to dilated cardiomyopathy.

Patients.  Fifty‐four patients (42 men and 12 women, mean age 50 years) were studied. There were three patients in NYHA (New York Heart Association) functional class I, 32 patients in class II and 19 patients in class III.

Methods.  Measurements of plasma renin activity (PRA), plasma angiotensin II (A II) concentration and plasma atrial natriuretic peptide (ANP) concentration were made at rest and also in a subgroup (n = 32) during exercise. The urinary excretion of aldosterone was also determined. Investigations were performed at baseline, and after 3 and 6 months. Therapy was then stopped and the patients were re‐investigated 1 month thereafter.

Results.  The mean level of PRA was normal at baseline, reduced during therapy with metoprolol, and increased during therapy with captopril. The mean plasma concentration of A II was reduced during exercise and there was a trend towards a reduction even at rest in the metoprolol group, but not in the captopril group. The urinary excretion of aldosterone decreased in both groups. The mean plasma concentration of ANP was elevated at baseline and declined during exercise in the metoprolol group.

Conclusion.  In patients with dilated cardiomyopathy and only a partly activated renin–angiotensin system, both metoprolol and captopril reduced urinary excretion of aldosterone. Furthermore, metoprolol suppressed the exercise‐induced increase in ANP, suggesting a favourable effect on ventricular performance.
Atherosclerosis seems not to be associated with hyperinsulinaemia in patients with familial hypercholesterolaemia
Authors: Raal F. J. , Panz V. R. , Pilcher G. J. , Joffe B. I.
Published: March 2003

Objective. To study the relationship between hyperinsulinaemia, insulin resistance, leptin and atherosclerosis in subjects with familial hypercholesterolaemia (FH).

Design. Case‐control cross‐sectional study.

Setting. Lipid clinic, Johannesburg Hospital, South Africa.

Subjects and methods. Fasting serum lipid, glucose, insulin and leptin levels were measured in 24 homozygous FH subjects; 20 FH heterozygotes without coronary artery disease (CAD); 22 heterozygotes with documented CAD; and 20 healthy normocholesterolaemic subjects. Insulin resistance was calculated using the homeostasis model assessment (HOMA) formula.

Results. Mean glucose and insulin levels were similar in all 4 groups. There was no significant difference in calculated insulin resistance between any of the groups. There was also no relationship between the degree of insulin resistance and total or LDL‐cholesterol levels. Using Spearman’s correlation coefficient (Rs) calculated insulin resistance correlated with triglyceride (Rs = 0.27; P < 0.05) and inversely with HDL‐cholesterol (Rs = – 0.26; P < 0.05). Fasting insulin concentrations and calculated insulin resistance were similar in FH subjects with overt CAD compared to those without. Leptin levels were higher in the FH subjects with CAD. However, these subjects were older and had a larger body mass index (BMI), and when adjusted for age and BMI, only BMI correlated with leptin levels (multiple r = 0.65; P < 0.001).

Conclusions. In the absence of other causes of insulin resistance, FH subjects have normal fasting insulin levels and, in general, they are not insulin resistant. Insulin resistance appears to play little role in the pathogenesis of accelerated atherosclerosis in FH.
Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin
Authors: Mogyorósi A. , Bradley B. , Showalter A. , Schubert M. L.
Published: March 2003

Abstract. Mogyorósi A, Bradley B, Showalter A, Schubert ML (Medical College of Virginia/Virginia Commonwealth University and Hunter Holmes McGuire VAMC, Richmond, Virginia, USA). Rhabdomyolysis and acute renal failure due to combination therapy with simvastatin and warfarin (Case Report). J Intern Med 1999; 246: 599–602.

Simvastatin, an inhibitor of 3‐hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase, is widely used to treat hyperlipidaemia. Although myalgias are recognized adverse effects, clinically significant elevations in serum creatine phosphokinase (CPK) levels are uncommon. We describe a case of rhabdomyolysis and acute renal failure associated with concomitant use of simvastatin and warfarin. Rhabdomyolysis and renal failure occurred 7 days after warfarin (5 mg day–1) was added to a chronic stable dose of simvastatin (20 mg day–1) and resolved abruptly after discontinuation of simvastatin. We recommend careful monitoring when warfarin is given to patients receiving simvastatin.
Studies in hypertriglyceridaemia VI: serum lathosterol concentration is raised in hypertriglyceridaemic non‐diabetic males with hyperinsulinaemia
Authors: Asplund‐Carlson A. , Lund E. , Björkhem I. , Carlson L. A.
Published: March 2003

Objectives. To assess the cholesterol synthesis rate in primary hypertriglyceridaemia using the serum unesterified lathosterol concentration as an indicator.

Design. A cross‐sectional, case–control study.

Setting. The Karolinska Hospital, Stockholm.

Subjects. Randomly selected hyper‐ (n = 53) and normotriglyceridaemic (n = 57) males, 40–50 years, with a fasting serum triglyceride concentration (mean ± SD) of 3.81 ± 1.65 and 1.28 ± 0.53 mmol L−1, respectively. The exclusion criterion was diabetes mellitus, defined according to the World Health Organization (WHO) guidelines.

Main outcome measures. To compare the fasting serum concentration distributions of lathosterol, a cholesterol precursor, in hyper‐ and normotriglyceridaemic groups.

Results. Thirty‐six per cent of the hypertriglycerdaemic group had raised serum lathosterol concentrations, based on the 90th percentile of the lathosterol distribution of the normotriglyceridaemic group. In the hyper‐ but not in the normotriglyceridaemic group, lathosterol concentration was directly correlated with serum insulin responses to oral (r = 0.38; P = 0.007) and intravenous (r = 0.41; P = 0.005) glucose challenges.

Conclusions. One‐third of a randomly selected non‐diabetic hypertriglyceridaemic population had an increased serum lathosterol concentration and this might indicate an increased cholesterol synthesis rate compatible with increased production of VLDL particles, possibly as the result of chronic hyperinsulinaemia.
Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation
Authors: Ceremużyński L. , Gębalska J. , Wołk R. , Makowska E.
Published: March 2003

Abstract. Ceremużyński L, Gębalska J, Wołk R, Makowska E (Klinika Kardiologii CMKP, Szpital Grochowski, Warszawa, Poland). Hypomagnesemia in heart failure with ventricular arrhythmias. Beneficial effects of magnesium supplementation. J Intern Med 2000; 247: 78–86.

Objective. To assess the role of electrolyte imbalance in cardiac arrhythmias associated with congestive heart failure.

Design. Serum magnesium and potassium levels, urine magnesium excretion and the incidence of ventricular arrhythmias were assessed throughout the study. The patients who displayed complex arrhythmias after the first week of hospital medication were randomized 2 : 1 to double‐blind magnesium supplementation or placebo.

Setting. The study was carried out in one municipal hospital, providing primary care.

Subjects. A total of 588 consecutive patients were screened for eligibility (clinical heart failure ≥6 months; NYHA class II‐IV; left ventricular ejection fraction ≤40%; sinus rhythm; serum creatinine ≤2 mg dL–1). A total of 78 patients entered and 68 patients completed the study.

Interventions. Intravenous administration of magnesium (magnesium sulphate 8 g in 250 mL of 5% glucose) or placebo (250 mL of 5% glucose) over 12 h.

Main outcome measures. (i) Incidence of ventricular arrhythmias in patients with hypomagnesemia; (ii) effects of magnesium supplementation on ventricular arrhythmias.

Results. On admission, hypomagnesemia was found in 38% and excessive magnesium loss in 72% of patients. Serum magnesium levels were lower and urine magnesium excretion was greater in patients with complex ventricular arrhythmias, both on admission and after treatment for heart failure. Intravenous administration of magnesium caused a significant decrease in the number of ventricular ectopic beats (P < 0.0001), couplets (P < 0.003) and episodes of nonsustained ventricular tachycardia (P < 0.01).

Conclusions. Hypomagnesemia, probably related to increased urine magnesium excretion, is an essential feature of heart failure associated with complex ventricular arrhythmias. These arrhythmias can be alleviated/abolished by magnesium supplementation.
The distribution of two different vitamin D receptor polymorphisms (BsmI and start codon) in primary hyperparathyroidism
Authors: Sosa M. , Torres A. , Martín N. , Salido E. , Limiñana J. M. , Barrios Y. , De Miguel E. , Betancor P.
Published: March 2003

Abstract. Sosa M, Torres A, Martín N, Salido E, Limiñana JM, Barrios Y, de Miguel E, Betancor P (University Hospital Insular, Bone Metabolic Unit, University of Las Palmas de Gran Canaria, Las Palmas and University of La Laguna, Canary Islands, Spain). The distribution of two different vitamin D receptor polymorphisms (BsmI and start codon) in primary hyperparathyroidism. J Intern Med 2000; 247: 124–130.

Introduction. The bb genotype of the BsmI polymorphism of the vitamin D receptor (VDR) is more common in primary hyperparathyroidism (HPT) than in the general population in Swedish and German women. However, little is known about the association of HPT with the start codon polymorphism of the VDR (defined by FokI).

Objective. To study the distribution of the VDR genotypes in a group of women with HPT compared with a control group. The bone mineral density (BMD) of different genotypes was also investigated.

Methods. VDR alleles were typed by polymerase chain reaction (PCR) assay around the polymorphic BsmI or FokI restriction sites in 67 control women (48.5 ± 10 years) and 53 women with HPT (61.4 ± 11 years). They were all Caucasian and born in the Canary Islands. Lumbar and proximal femur BMDs were measured by dual X‐ray absorptiometry (DXA) and quantitative computed tomography (QCT).

Results. The ‘bb’ genotype was equally frequent in controls and HPT subjects (46.3 and 45.3%, respectively). There was a trend towards a lower prevalence of the FF genotype amongst women with HPT as compared with controls (41.5 vs. 57.1%; P = 0.09). BMD was lower in patients with HPT compared with controls in the lumbar spine and the proximal femur.

Conclusions. The association of the BsmI polymorphism of the VDR gene with HPT is not applicable to all geographical areas. In Canarian postmenopausal women suffering from HPT, VDR genotype distribution is similar to that found in controls. A possible association of HPT with the FokI polymorphism deserves further investigation.
Dietary and other non‐pharmacological treatments in patients with drug‐treated hypertension and control subjects
Authors: Silaste M.‐L. , Junes R. , Rantala A. O. , Kauma H. , Lilja M. , Savolainen M. J. , Reunanen A. , Kesäniemi Y. A.
Published: March 2003

Abstract. Silaste M‐L, Junes R, Rantala AO, Kauma H, Lilja M, Savolainen MJ, Reunanen A, Kesäniemi YA (University of Oulu, Oulu, and The National Public Health Institute, Helsinki, Finland). Dietary and other non‐pharmacological treatments in patients with drug‐treated hypertension and control subjects. J Intern Med 2000; 247: 318–324.

Objective. To study the nutrient intakes and other lifestyle patterns of drug‐treated hypertensives and control subjects.

Design. A cross‐sectional population‐based epidemiological study.

Setting. The participating study subjects visited the research laboratory of the Department of Internal Medicine of the University of Oulu, Oulu, Finland.

Participants. A total of 1045 Finnish men and women aged 40–60 years, of whom 716 (69%) completed 7‐day food records.

Main outcome measures. Intakes of energy, protein, total fat, saturated, monounsaturated and polyunsaturated fatty acids, carbohydrate, alcohol, fibre, calcium, magnesium, potassium and sodium were assessed from 7‐day food records. The study also included measurements of blood pressure, blood glucose and plasma lipids, and anthropometric variables. Information about alcohol consumption, smoking habits and physical activity was collected by interviewing.

Results. Obesity was common amongst the hypertensive subjects, whose body mass indices were significantly higher than those of the control subjects. Only minor differences existed in the energy intake levels and nutrient intakes of the hypertensive and control cohorts, but the control subjects performed more physical activity than the hypertensive subjects. The dietary recommendations concerning the intakes of total and saturated fats, carbohydrate and fibre were poorly met by both the hypertensive and the control subjects. Alcohol consumption was high amongst the hypertensive men, especially amongst the smokers.

Conclusions. Non‐pharmacological treatment, including dietary management, of hypertensive patients at high risk for cardiovascular complications seems still to be inadequate. Additional well‐focused efforts are needed to intensify the dietary treatment as well as to reduce alcohol consumption and smoking amongst hypertensives.
Increased plasma concentrations of TGF‐β1 after hormone replacement therapy
Authors: Djurovic S. , Os I. , Hofstad A. E. , Abdelnoor M. , Westheim A. , Berg K.
Published: March 2003

Abstract. Djurovic S, Os I, Hofstad AE, Abdelnoor M, Westheim A, Berg K (Ullevål University Hospital and the University of Oslo, Oslo, Norway). Increased plasma concentrations of TGF‐β1 after hormone replacement therapy. J Intern Med 2000; 247: 279–285.

Objectives and design.   Hormone replacement therapy (HRT) in postmenopausal women may reduce the cardiovascular risk. A dominant protective role of transforming growth factor beta (TGF‐β1) on coronary arteries has been proposed. Lp(a) lipoprotein may block the activation of latent TGF‐β1. Given this background, we examined the effects of HRT on TGF‐β1 and Lp(a) lipoprotein in 99 postmenopausal women. The women had angiographically documented coronary heart disease (CHD) and were randomized to either sequential transdermal 17β‐oestradiol for 14 weeks and then medroxyprogesterone (MPA) for 14 days (HRT) or to a control group (C).

Results. Serum levels of TGF‐β1 were increased in the HRT group compared with the C group after 3 months’ treatment and this effect was sustained after 12 months. There was a significant reduction in Lp(a) lipoprotein serum levels after 3 months’ treatment in the HRT group compared with the C group. However, after 12 months, no significant difference in changes in Lp(a) lipoprotein serum levels was detected between the two groups.

Conclusion. The novel observation that transdermal 17β‐oestradiol in postmenopausal women increases levels of TGF‐β1 and lowers the concentration of Lp(a) lipoprotein suggests yet another possible mechanism for the cardioprotective effect of HRT. Whereas combination therapy of oestradiol and MPA preserves the beneficial effect on TGF‐β1, it reduces the unopposed oestradiol effects on Lp(a) lipoprotein.
Disease‐related syncope. Analysis of a community‐based hospital registry
Authors: Bandinelli G. , Cencetti S. , Bacalli S. , Lagi A.
Published: March 2003

Abstract. Bandinelli G, Cencetti S, Bacalli S, Lagi A (Ospedale Santa Maria Nuova, Firenze, Italy). Disease‐related syncope. Analysis of a community‐based hospital registry. J Intern Med 2000; 247: 513–516.

Syncope is characterized by sudden and transient loss of consciousness that follows a reduction or interruption of cerebral blood flow. The present study was designed to assess the prevalence of disease‐related syncope in a wide sample of in‐patients admitted for different diseases. A total of 16 809 patients (age range 18–99 years) were recruited from three hospitals in Florence in 1998. The community‐based registry was reviewed to identify all patients suffering from complaints associated with syncope. Each disease‐related syncope was matched with the number of patients suffering from that disease. Furthermore, each disease was expressed as a percentage of total cases included in the study. The odds ratio was calculated to determine the index of significant correlation between syncope and occasional diseases. Total syncopes were 775 (prevalence 4.46%), vasovagal syncopes were 336 (1.9% of total sample and 44% of total syncopes), and the disease‐related syncopes were 439 (56% of total syncopes). We found a significant association between syncope and orthostatic hypotension, complete heart block, chronic cerebral disease, migraine, acute gastrointestinal haemorrhages and aortic stenosis. Furthermore, we found a significant association with acute gastrointestinal haemorrhage, which has not been described previously. Significant relationships emerged from our data which yield a new insight into the association between syncope and a wide range of systemic diseases.
Immune responses to oxidative neoepitopes on LDL and phospholipids modulate the development of atherosclerosis
Authors: Palinski W. , Witztum J. L.
Published: March 2003

Abstract. Palinski W, Witztum JL (University of California San Diego, La Jolla, California, USA). Immune responses to oxidative neoepitopes on LDL and phospholipids modulate the development of atherosclerosis (Minisymposium). J Intern Med 2000; 247: 371–380.

Extensive evidence suggests that humoral and cellular immune responses against lipid peroxidation products occur in vivo and that they modulate the progression of atherosclerosis. The biological significance of these immune responses is the focus of this review. Lipid peroxidation generates reactive aldehydes and oxidized phospholipids which form complex, immunogenic adducts with proteins or other phospholipids. Autoantibodies against oxidative neoepitopes are present in humans and other species and their titre may be an indicator of the extent of atherosclerosis. Interventions boosting immune responses to oxidized LDL reduce the progression of atherosclerosis in animal models. However, other interventions inhibiting immune cells or signalling factors enhance atherogenesis, suggesting that different elements of the immune system exert opposite effects. Evaluation of the role of immune mechanisms in atherosclerosis is further complicated by the fact that other chronic inflammatory conditions induce similar humoral immune responses to oxidative neoepitopes, in particular oxidized phospholipids. Naturally occurring antibodies cloned from atherosclerotic mice provide insights into the nature of antigens formed in vivo and on biological effects of some antibody populations. For example, antibodies to oxidized phospholipid adducts inhibit macrophage uptake of oxidized LDL by blocking scavenger receptors. Antibodies to oxidation‐specific epitopes may also be suitable for non‐invasive diagnosis of atherosclerosis.
A comparison between patients suffering in‐hospital and out‐of‐hospital cardiac arrest in terms of treatment and outcome
Authors: Herlitz J. , Bång A. , Ekström L. , Aune S. , Lundström G. , Holmberg S. , Holmberg M. , Lindqvist J.
Published: March 2003

Abstract. Herlitz J, Bång A, Ekström L, Aune S, Lundström G, Holmberg S, Holmberg M, Lindqvist J (Sahlgrenska University Hospital, Göteborg, Sweden). A comparison between patients suffering in‐hospital and out‐of‐hospital cardiac arrest in terms of treatment and outcome. J Intern Med 2000; 248: 53–60.

Aim. To compare treatment and outcome amongst patients suffering in‐hospital and out‐of‐hospital cardiac arrest in the same community.

Patients. All patients suffering in‐hospital cardiac arrest in Sahlgrenska University Hospital covering half the catchment area of the community of Göteborg (500 000 inhabitants) and all patients suffering out‐of‐hospital cardiac arrest in the community of Göteborg. Criteria for inclusion were that resuscitation efforts should have been attempted.

Time of survey. From 1 November 1994 to 1 November 1997.

Methods. Data were recorded both prospectively and retrospectively.

Results. In total, 422 patients suffered in‐hospital cardiac arrest and 778 patients suffered out‐of‐hospital cardiac arrest. Patients with in‐hospital cardiac arrest included more women and were more frequently found in ventricular fibrillation. The median interval between collapse and defibrillation was 2 min in in‐hospital cardiac arrest compared with 7 min in out‐of‐hospital cardiac arrest (< 0.001). The proportion of patients being discharged from hospital was 37.5% after in‐hospital cardiac arrest, compared with 8.7% after out‐of‐hospital cardiac arrest (P < 0.001). Corresponding figures for patients found in ventricular fibrillation were 56.9 vs. 19.7% (P < 0.001) and for patients found in asystole 25.2 vs. 1.8% (P < 0.001).

Conclusion. In a survey evaluating patients with in‐hospital and out‐of‐hospital cardiac arrest in whom resuscitation efforts were attempted, we found that the former group had a survival rate more than four times higher than the latter. Possible strong contributing factors to this observation are: (i) shorter time interval to start of treatment, and (ii) a prepared selection for resuscitation efforts.
Polymorphisms of the β2‐adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men
Authors: Rosmond R. , Ukkola O. , Chagnon M. , Bouchard C. , Björntorp P.
Published: March 2003

Abstract. Rosmond R, Ukkola O, Chagnon M, Bouchard C & Björntorp P (Department of Heart and Lung Diseases, Göteborg University, Sweden; Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA; Department of Internal Medicine, University of Oulu, Oulu, Finland). Polymorphisms of the β2‐adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men. J Intern Med 2000; 248: 239–244.

Objective. To investigate the effect of polymorphisms in codon 16 (Arg16Gly) and codon 27 (Gln27Glu) of the β2‐adrenergic receptor gene (ADRB2) on anthropometric, endocrine, metabolic and haemodynamic variables.

Design. A cross‐sectional study.

Subjects. A subgroup of 284 Swedish men from a population sample of 1040 at the age of 51 years.

Main outcome measures. Genotype examination of ADRB2 polymorphisms in codon 16 and codon 27 with polymerase chain reaction and restriction fragment length polymorphism. Anthropometric measurements included body mass index, waist‐to‐hip ratio and abdominal sagittal diameter. Endocrine measurements included blood levels of testosterone, insulin‐like growth factor I, and leptin plus salivary cortisol. Overnight fasting values of serum insulin, blood glucose, triglycerides, total, low and high density lipoprotein cholesterol, as well as blood pressure and resting heart rate, were also determined.

Results.   Polymorphisms were frequent in both codon 16 and codon 27. The Arg16Gly genotype showed significant relationships to elevated central distribution of body fat and to systolic blood pressure, whilst the Glu27Glu genotype was associated with elevated leptin and triglyceride levels but not to other measurements, including obesity variables.

Conclusions.   We conclude that only a few cardiovascular risk factors are associated with DNA sequence variation in the ADRB2 in Swedish men.
A pilot study of streptokinase‐induced endothelial injury and platelet activation following acute myocardial infarction
Authors: Lip G. Y. H. , Lydakis C. , Nuttall S. L. , Landray M. J. , Watson R. D. S. , Blann A. D.
Published: March 2003

Abstract. Lip GYH, Lydakis C, Nuttall SL, Landray MJ, Watson RDS, Blann AD (Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK). A pilot study of streptokinase‐induced endothelial injury and platelet activation following acute myocardial infarction. J Intern Med248: 316–318.

Objective. To relate the changes in serum vitamin E, an essential antioxidant, to changes in fibrinogen, as well as indices of endothelial damage [as indicated by plasma markers, soluble thrombomodulin (sTM) and von Willebrand factor (vWf)], and an index of platelet activation [soluble P selectin (sPsel)], in myocardial infarction treated with thrombolytic therapy.

Design and Setting. Prospective longitudinal pilot study in a teaching hospital Coronary Care Unit.

Subjects and intervention. Seventeen patients (12 men; mean age 62 years ± SD 11 years) admitted with acute myocardial infarction (AMI), who were given thrombolytic therapy, and 59 healthy controls.

Results. Baseline levels of fibrinogen (Mann–Whitney test, P = 0.0055) and vWf (P < 0.001) were significantly higher than controls, but sPsel, sTM or vitamin E levels were not significantly different. Following thrombolysis, as expected, median concentrations of plasma fibrinogen fell profoundly (Friedman
anovaP < 0.001) so that after 45 min, levels were undetectable in 13 patients. At 24‐h median fibrinogen concentration had recovered to approximately 30% of baseline (P < 0.01) and was still undetectable in three patients. Levels of vWf and sPsel increased steadily, reaching significance after three hours (both P < 0.05). However, levels of sTM rose immediately after thrombolysis, peaking between 1 and 3 h, and remained elevated at 24 h. These increases corresponded to a simultaneous early fall in serum vitamin E concentrations.

Conclusion. The present pilot study demonstrates significant endothelial damage and platelet activation in association with increased oxidative stress following streptokinase therapy for AMI.
The inpatient care of patients with diabetes mellitus and foot ulcers. A validation study of the correspondence between medical records and the Swedish Inpatient Registry with the consequences for cost estimations
Authors: Ragnarson Tennvall G. , Apelqvist J. , Eneroth M.
Published: March 2003

Abstract. Ragnarson Tennvall G, Apelqvist J, Eneroth M (Swedish Institute for Health Economics and Departments of Internal Medicine and Orthopaedics, Lund University Hospital, Lund, Sweden). The inpatient care of patients with diabetes mellitus and foot ulcers. A validation study of the correspondence between medical records and the Swedish Inpatient Registry with the consequences for cost estimations. J Intern Med 2000; 248: 397–405.

Objectives. To compare the correspondence of discharges and diagnoses between medical records and an administrative database in diabetic patients with foot ulcers and to calculate inpatient costs from the different sources.

Design. Discharge data from 117 prospectively followed patients were compared with information from the Swedish Inpatient Registry during the same treatment period for each patient. Non corresponding discharges were retrospectively reviewed in patient records. Costs of inpatient care were calculated from clinical sources and from data selected in three different ways from the database. Information in medical records was assumed to represent the ‘Gold Standard’.

Setting. In‐hospital treatment, multidisciplinary foot‐care team.

Subjects. A total of 117 diabetic patients with deep foot infections.

Main outcome measures. Degree of database completeness and inpatient costs.

Results. The degree of completeness of discharges in the database was 98%, but 8.6% of discharges had no code for diabetes and 13% were registered without any foot related diagnosis code. Less than 20% of discharges were found with selection based on primary diagnosis 250.G only. Total inpatient costs varied from 2.7 to 13.3 million SEK (Swedish Kronor) depending on selected diagnosis codes. Approximately 84% of all foot ulcer discharges could be found in the database if codes with both diabetes mellitus and foot ulcer diagnoses were selected.

Conclusions. Inpatient costs for foot complications cannot be accurately estimated from the Inpatient Registry when based on primary diagnosis exclusively. Fairly good estimates at a low data acquisition cost can be made with a combination of foot related diagnoses together with codes for diabetes.
Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3‐year progression of carotid atherosclerosis
Authors: Salonen J. T. , Nyyssönen K. , Salonen R. , Lakka H.‐M. , Kaikkonen J. , Porkkala‐Sarataho E. , Voutilainen S. , Lakka T. A. , Rissanen T. , Leskinen L. , Tuomainen T.‐P. , Valkonen V.‐P. , Ristonmaa U. , Poulsen H. E.
Published: March 2003

Abstract. Salonen JT, Nyyssönen K, Salonen R, Lakka H‐M, Kaikkonen J, Porkkala‐Sarataho E, Voutilainen S, Lakka TA, Rissanen T, Leskinen L, tuomainen T‐P, Valkonen V‐P, Ristonmaa U (University of Kuopio, Finland), Poulsen HE (University of Copenhagen, Copenhagen, Denmark). Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study: a randomized trial of the effect of vitamins E and C on 3‐year progression of carotid atherosclerosis. J Intern Med 2000; 248: 377–386.

Objectives. To study the efficacy of vitamin E and C supplementation on the progression of carotid atherosclerosis, hypothesizing an enhanced preventive effect in men and in smokers and synergism between vitamins.

Design and subjects. Double‐masked two‐by‐two factorial trial, randomization in four strata (by gender and smoking status) to receive twice daily either 91 mg (136 IU) of d‐α‐tocopherol, 250 mg of slow‐release vitamin C, a combination of these or placebo for three years. A randomized sample of 520 smoking and nonsmoking men and postmenopausal women aged 45–69 years with serum cholesterol ≥ 5.0 mmol L–1 were studied.

Setting. The population of the city of Kuopio in Eastern Finland.

Intervention. Twice daily either a special formulation of 91 mg of d‐α‐tocopherol, 250 mg of slow‐release vitamin C, a combination of these (CellaVie®) or placebo for three years.

Measurements. Atherosclerotic progression, defined as the linear regression slope of ultrasonographically assessed common carotid artery mean intima–media thickness (IMT), was calculated over semi‐annual assessments.

Results. The average increase of the mean IMT was 0.020 mm year–1 amongst men randomized to placebo and 0.018 mm year–1 in vitamin E, 0.017 mm year–1 in vitamin C and 0.011 mm year–1 in the vitamin combination group (P = 0.008 for E + C vs. placebo). The respective means in women were 0.016, 0.015, 0.017 and 0.016 mm year–1. The proportion of men with progression was reduced by 74% (95% CI 36–89%, P = 0.003) by supplementation with the formulation containing both vitamins, as compared with placebo.

Conclusions. Our study shows that a combined supplementation with reasonable doses of both vitamin E and slow‐release vitamin C can retard the progression of common carotid atherosclerosis in men. This may imply benefits with regard to other atherosclerosis‐based events.
Trends in long‐term survival after myocardial infarction: less favourable patterns for patients from deprived areas
Authors: Engström G. , Göransson M. , Hansen O. , Hedblad B. , Tydén P. , Tödt T. , Janzon L.
Published: March 2003

Abstract. Engström G, Göransson M, Hansen O, Hedblad B, Tydén P, Tödt T, Janzon L (Malmö University Hospital, Malmö, Sweden). Trends in long‐term survival after myocardial infarction: less favourable patterns for patients from deprived areas. J Intern Med 2000; 248: 425–434.

Objective. New treatments have improved the prognosis for patients with acute myocardial infarction. However, studies on long‐term survival are not unequivocally in favour of an improved long‐term prognosis. This study aimed to analyse trends in 3‐year survival in relation to sex, age and socioeconomic level of residential area.

Setting. The Malmö myocardial infarction register, Sweden.

Participants. All men and women in the city who, between 1978 and 1995, were admitted for a first acute myocardial infarction (n = 11 226).

Main outcome measures. Age‐standardized 3‐year survival rates.

Results. Both 28‐day and 3‐year survival rates improved markedly during the study period. Age‐standardized 3‐year survival (per 100 patients) amongst men and women who survived 28 days increased, between 1978–81 and 1991–95, from 64 to 78 in men and from 66 to 77 in women, an annual increase of 1.4% (95% CI = 1.1–1.7) and 1.2% (0.8–1.5), respectively. There were marked differences in survival between residential areas with different socioeconomic circumstances. The 3‐year survival rates amongst men correlated significantly with the socioeconomic circumstances in the areas expressed in terms of a socioeconomic score (men: r = 0.60, n = 17, P = 0.01; women: r = 0.37, P = 0.15). Trends tended to be less favourable in deprived areas.

Conclusion. Three‐year survival after first myocardial infarction has continuously improved for men and women in all age groups. Prognosis was worse and trends tended to be less favourable for patients from deprived areas.
Lentiviral‐mediated gene transfer into haematopoietic stem cells
Authors: Woods N.‐B. , Mikkola H. , Nilsson E. , Olsson K. , Trono D. , Karlsson S.
Published: March 2003

Abstract. Woods N‐B, Mikkola H, Nilsson E, Karin O, Trono D, Karlsson S (Lund University Hospital, Sweden; and University of Geneva Medical School, Switzerland). Lentiviral‐mediated gene transfer into haematopoietic stem cells (Minisymposium). J Intern Med 2001; 249: 339–343.

Objectives. Lentiviral vectors can transduce nondividing cells. As most haematopoietic stem cells (HSCs) are nondividing in vivo, lentiviral vectors are promising viral vectors to transfer genes into HSCs.

Design and Setting. We have used HIV‐1 based lentiviral vectors containing the green fluorecent protein (GFP) gene to transduce umbilical cord blood CD34+ and CD34+/CD38– cells prior to transplantation into NOD/SCID mice.

Results. High level engraftment of human cells was obtained and transgene expression was seen in both myeloid and lymphoid lineages. Bone marrow from the primary transplant recipients mice was transplanted into secondary recipients. GFP expression was seen in both lymphoid and myeloid cells in the secondary recipients 6 weeks posttransplantation. Human haematopoietic progenitor colonies were grown from both primary and secondary recipients. Over 50% of the haematopoietic colonies in these recipients were positive for the GFP transgene by PCR. Following inverse PCR, amplified fragments were sequenced and integration of the vector into human genomic DNA was demonstrated. Several vectors containing different internal promoters were tested in NOD/SCID mice that had been transplanted with transduced CD34+ and CD34+/CD38– cells. The elongation factor‐1α (EF‐1α) promoter gave the highest level of expression, both in the myeloid and lymphoid progeny of the engrafting cells.

Conclusions. These data collectively indicate that candidate human HSCs can be efficiently transduced with lentiviral vectors and that the transgene is highly expressed in their progeny cells.
Homocysteine and major coronary events: a prospective population study amongst women
Authors: Knekt P. , Alfthan G. , Aromaa A. , Heliövaara M. , Marniemi J. , Rissanen H. , Reunanen A.
Published: March 2003

Abstract. Knekt P, Alfthan G, Aromaa A, Heliövaara M, Marniemi J, Rissanen H, Reunanen A (National Public Health Institute, Helsinki, and Social Insurance Institution, Turku, Finland). Homocysteine and major coronary events; a prospective population study amongst women. J Intern Med 2001; 249: 461–465.

Objectives. To study serum homocysteine concentration for its prediction of major coronary heart disease events amongst women.

Design. A case‐control study nested within a follow‐up study.

Subjects. A total of 74 and 75 major coronary events (coronary deaths or nonfatal myocardial infarction) which occurred in women with and without known heart disease, respectively, during a 13‐year follow‐up and two individually matched controls per case.

Main outcome measure. Major coronary event.

Results. Amongst women with baseline heart disease, the relative risk (95% CI) of such events, adjusted for age, smoking, hypertension, diabetes, serum cholesterol and body mass index, was 3.32 (1.05–10.5) in the highest homocysteine quintile compared with the lowest quintile. Amongst women free of heart disease at baseline, the corresponding relative risk value was 0.77 (0.24–2.45).

Conclusions. This prospective study support the hypothesis that homocysteine is a risk factor for coronary events in women with heart disease.
Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity
Authors: Hillege H. L. , Janssen W. M. T. , Bak A. A. A. , Diercks G. F. H. , Grobbee D. E. , Crijns H. J. G. M. , Van Gilst W. H. , De Zeeuw D. , De Jong P. E. ,   FOR THE PREVEND STUDY GROUP
Published: March 2003

Abstract. Hillege HL, Janssen WMT, Bak AAA, Diercks GFH, Grobbee DE, Crijns HJGM, van Gilst WH, de Zeeuw D, de Jong PE for the PREVEND Study group (University of Groningen and University Hospital Groningen, Groningen; University Medical centre, Utrecht, the Netherlands). Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern Med 2001; 249: 519–526.

Objectives. To assess the prevalence of microalbuminuria in the general population, especially in nondiabetic and nonhypertensive subjects, and its association with known cardiovascular risk factors and cardiovascular morbidity.

Design. Cross‐sectional cohort study.

Setting. Inhabitants of the city of Groningen, the Netherlands.

Subjects. All inhabitants, aged between 28 and 75 years, were send a postal questionnaire and a vial to collect an early morning urine sample (n=85 421). Of these 40 856 subjects (47.8%) responded. Cardiovascular risk factors and morbidity were validated in a well defined nondiabetic and nonhypertensive group of 5241 subjects.

Main outcome measures. Microalbuminuria, self‐reported cardiovascular risk and cardiovascular morbidity in the total study cohort, and additionally more detailed measurements in a subset of the total population.

Results. Microalbuminuria (20–200 mg L–1) was present in 7.2% of the subjects and independently associated with age, gender, hypertension, diabetes, smoking, previous myocardial infarction and stroke. Some of these associations were already observed at albuminuria levels of 10–20 mg L–1. After exclusion of the diabetic and hypertensive subjects, microalbuminuria was still prevalent in 6.6% of the subjects.

Conclusions. Microalbuminuria appears to be common not only in the general population but also in a nondiabetic, nonhypertensive population and is independently associated with increased cardiovascular risk factors and cardio‐vascular morbidity. Importantly, some of these associations are present at urinary albumin levels currently considered to be normal. These findings suggest that urinary albumin measurements may be useful in early risk profiling and prevention of cardiovascular disease in the population at large.
Hypercalcaemia of malignancy: an undiagnosed and undertreated disease
Authors: Lamy O. , Jenzer‐Closuit A. , Burckhardt P.
Published: March 2003

Lamy O, Jenzer‐Closuit A, Burckhardt P (University Hospital, Lausanne, Switzerland). Hypercalcaemia of malignancy: an undiagnosed and undertreated disease. J Intern Med 2001; 250: 73–79.

Background. Hypercalcaemia of malignancy, a relatively frequent phenomenon, seems to be insufficiently recognized and treated. Its symptoms are not specific, but they affect the quality of life.

Methods. A prospective study to analyse the influence of symptoms caused by hypercalcaemia on the decision of the admitting physician, the motivation for treatment, and the effect of the treatment on the given symptoms in hospitalized patients with oncologic disease in progression, where confounding causes of similar symptoms such as cerebral metastasis, radiotherapy, treatment with opioids, etc., were excluded.

Results. A total of 71 patients, mean age 65 + 11 years, fulfilled the strict inclusion criteria. About 42% were hospitalized because of symptoms caused by hypercalcaemia, but none of the medical reports mentioned hypercalcaemia as reason for hospitalization. Specific antihypercalcaemic therapy was given to only 37% of patients, and only 25% got an adequate rehydratation. Antihypercalcaemic treatment was guided by the severity of hypercalcaemia (>3.00 mmol L–1), not by the symptoms. Polyuria‐polydipsia, nausea‐vomiting and constipation were correlated with hypercalcaemia. These symptoms, as well as confusion‐stupor and bone pains improved significantly when calcaemia was normalized. Patients with calcaemia normalized returned home most frequently (P < 0.03).

Conclusions. Malignant hypercalcaemia remains mostly undiagnosed in medical praxis. Specific treatment occurs in too small fractions of the patients. As the normalization of calcaemia significantly improves the symptoms because of hypercalcaemia and the quality of life, rapid rehydration and specific calcium lowering treatments should be part of palliative measures in all patients with malignant hypercalcaemia.
Sleep disturbance in association with elevated pulse rate for prediction of mortality – consequences of mental strain?
Authors: Nilsson P. M. , Nilsson J.‐Å. , Hedblad B. , Berglund G.
Published: March 2003

Abstract. Nilsson PM, Nilsson J‐Å, Hedblad B, Berglund G (University Hospital, Malmö, Sweden). Sleep disturbance in association with elevated pulse rate for prediction of mortality – consequences of mental strain? J Intern Med 2001; 250: 521–529.

Objectives. Sleep deprivation has experimentally been shown to adversely influence glucose metabolism, endocrine function and sympathovagal balance in young men without known serious disease. We investigated the impact of sleep problems and resting heart rate in a large sample of self‐reported, healthy middle‐aged men and women on long‐term mortality.

Methods. In all 22 444 men and 10 902 women participated in a population‐based health screening (71% mean attendance), including blood sampling and examination of blood pressure (BP) and pulse rate after 10 min supine rest, as well as a self‐administered questionnaire on sleep problems. Mortality was assessed from national death registers.

Results. Sleep disturbances were related to increased cardiovascular risk factor levels at baseline in both sexes, and predicted total and cause‐specific mortality after a mean of 12 years (women) and 17 years (men) of follow‐up. In men, self‐reported healthy at baseline, total mortality during follow‐up was independently predicted by both sleep problems and increased resting heart rate, also after adjustment for smoking, body mass index (BMI), systolic BP, cholesterol, smoking and problematic alcohol drinking habits. A step‐wise increased total mortality was shown in men reporting successively worse sleep problems and higher heart rate, highest hazard ratio 2.7 [95% confidence interval (CI)=2.1–3.4] after adjustments, compared with men free from sleep problems and with normal heart rate.

Conclusions. Sleep disturbance is a predictor of total and cause‐specific mortality in both sexes, but only interacts with increased resting heart rate for this prediction in healthy men. Sleep problems correlated cross‐sectional with disturbances in lipid and glucose metabolism, even after adjustment for degree of obesity and smoking. Sleep disturbance is a symptom for a biological pathway that is correlated to premature mortality. One possible explanation would be that it acts in concert with sympathetic nervous activation (SNA), both being consequences of chronic stress exposure.