bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterosexual transmission of hepatitis C virus and the possible role of coexistent human immunodeficiency virus infection in the index case: A multicentre study of 423 pairings
Authors: SOTO B. , RODRIGO L. , GARCIA‐BENGOECHEA M. , SANCHEZ‐QUIJANO A. , RIESTRA S. , ARENAS J. I. , ANDREU J. , RODRIGUEZ M. , EMPARANZA J. I. , TORRES Y. , NAVASCUÉS C. A. , CORTES A. , LISSEN E.
Published: August 2009

Abstract. Objectives. To define the role that sexual transmission plays in the spread of hepatitis C virus (HCV) infection, and to examine the influence of coexistent human immunodeficiency virus (HIV) infection on this mode of transmission.

Design. A multicentre, seroprevalence study of anti‐HCV performed in the stable heterosexual partners (SHP) of index cases reactive for anti‐HCV.

Setting. Department of Internal Medicine and Section of Gastroenterology of three University Hospitals, Spain.

Subjects. A total of 423 stable heterosexual partners of index cases reactive for anti‐HCV. This included a group of 142 intravenous drug users (IVDU), 120 of whom were coinfected with HIV. Additionally, 2886 first‐time voluntary blood donors selected at random were included to compare the prevalence of anti‐HCV.

Main outcome measures. Serum samples were screened for anti‐HCV by a commercially available, second‐generation enzyme‐linked immunoassay. Tests repeatedly reactive for anti‐HCV were analysed by a four‐antigen, recombinant immunoblot assay. Anti‐HIV was tested by enzyme immunoassay and Western blot was used for confirmation of positive cases.

Results. The prevalence of anti‐HCV, was 7.1% in SHP and 1.2% in random donors (P < 0.001). This prevalence was higher in SHP of index cases co‐infected with HIV in comparison with that shown in the SHP of index cases only reactive for the anti‐HCV (9.1 vs. 6.3%; P = 0.2), particularly when a younger and more homogeneous group such as the SHP of IVDU index cases was considered alone (9.2 vs. 0%; P = 0.1). However, the SHP of IVDU index cases coinfected with HIV were almost three times more likely to be infected with HIV than HCV (24.2 vs. 9.2%).

Conclusions. These data suggest that HCV infection may be sexually transmitted but with low efficiency, and this could be increased in the presence of coexistent HIV infection in the index case.
The influence of thrombolytic therapy on the predictive value of exercise testing 3 weeks after acute myocardial infarction
Authors: ABBOUD L. , HIR J. , EISEN I. , MARKIEWICZ W.
Published: August 2009

Abstract. Objectives. To evaluate the prognostic value of exercise testing performed soon after acute myocardial infarction (AMI) in patients treated with thrombolytic therapy.

Design. A 1‐year prospective follow‐up of 185 subjects treated with thrombolytic therapy who survived AMI, and who performed exercise testing 3 weeks after AMI. These patients were compared with 272 patients not receiving thrombolytic therapy during the same period.

Subjects. Patients recovering from AMI, without medical contraindications to exercise testing performed 3 weeks after AMI.

Main outcome measures. ST‐segment deviations during exercise testing 3 weeks post‐AMI were related to clinical outcome 1‐year post‐AMI and to the administration of thrombolytic therapy during the acute phase of infarction.

Results. In patients treated with thrombolytic therapy, the only exercise‐test‐related parameter predicting subsequent cardiac events was ST‐segment elevation. In contrast, patients not receiving thrombolytic therapy and demonstrating ST‐segment depression of ≥ 1 mm during exercise had more clinical cardiac events than those without this finding (12.3 vs. 3.9%; P < 0.05).

Conclusion. This study casts doubt on the ability of exercise testing to select a high‐risk population requiring early intervention to prevent recurrent coronary events after thrombolysis for AMI.
Strong link between the alpha1‐antitrypsin PiZ allele and Wegener's granulomatosis
Authors: ELZOUKI A.‐N. Y. , SEGELMARK M. , WIESLANDER J. , ERIKSSON S.
Published: August 2009

Abstract. Objectives. To ascertain whether a relationship exists between the PiZ alpha1‐antitrypsin (α1AT) variant and antineutrophil cytoplasm antibodies (ANCA)‐positive vasculitis in a large group of Swedish patients, and whether analysis for the presence of the PiZ variant might be useful for diagnostic or prognostic purposes.

Design. Retrospective cross‐sectional study.

Setting. The Department of Internal Medicine, Malmö General Hospital, and the Department of Nephrology, University of Lund, Sweden.

Subjects and main outcome measures. Serum samples from 105 proteinase 3‐ANCA‐positive patients were analysed using an elisa with a monoclonal antibody specific for the PiZ‐gene product. Complete clinical data were retrieved for 84% (88/105) of the patients, for diagnosis and survival analysis.

Results. We identified 17 heterozygotes and one homozygote (P < 0.0001). All 88 patients with available clinical data were considered to have some form of microscopic vasculitis including 66 (75%) diagnosed as having Wegener's granulomatosis (WG), of whom 15 (23%) were PiZ heterozygotes (odds ratio 6.0, 95% confidence interval 3–10). There were no significant differences between PiZ carriers and noncarriers in sex distribution, mean age at onset of disease, interval between onset and inclusion in the study, or in median duration of follow‐up (P > 0.2 for all comparisons). During follow‐up, 38% (6/16) of the PiZ heterozygotes died, compared with 17% (11/66) of noncarriers of the variant (P = 0.02), which suggests that PiZ heterozygosity may be a marker of poor prognosis. PiZ heterozygotes with systemic vasculitis would not appear to be identifiable by their pretreatment plasma α1AT concentrations, as all such patients in the present study had concentrations within or above the normal range.

Conclusion. We conclude that heterozygotes for the PiZ variant of the α1AT gene are at greater risk of than the general population of developing WG. Knowledge of such a genetic factor may not only aid our understanding of the mechanism involved in this illness but may also serve as significant prognostic factor in following the course of the disease.
Abdominal aortic aneurysms and alpha1‐antitrypsin
Authors: ELZOUKI A.‐N. Y. , ERIKSSON S.
Published: August 2009

Abdominal aortic aneurysms and alpha1‐antitrypsin deficiency

Abstract. The incidence of abdominal aortic aneurysms (AAAs) has been reported to be increased in heterozygous (PiMZ) and homozygous (PiZZ) alpha1‐antitrypsin (α1AT) deficiency. We report a further case of AAA in a PiSZ α1AT‐deficient female with primary biliary cirrhosis (PBC). Moreover, to assess the risk of AAA in patients with PiZZ α1AT deficiency, we conducted a retrospective study based on 30 consecutive autopsied adult cases of severe α1AT deficiency identified during the period 1963–1993 in the city of Malmö, Sweden, during which autopsies were performed in 49 548, or 58.4%, of all residents in the city who died. From the homozygote frequency in the general population, 50 of these would be expected to have α1AT deficiency. The disease had been diagnosed in 35, and autopsies had been performed in 30 adults. Each autopsied case was matched with four controls selected from the same autopsy register, and the Mantel‐Haenszel odds ratio (ORmh) was calculated. We found one case of AAA amongst the 30 PiZZ individuals autopsied, and one case amongst 120 autopsied controls (ORmh = 2.65, 95% confidence limits, 0.47–15.0; P = 0.273). We found no significant evidence of the relationship between AAA and the PiZZ polymorphism, although previously reported by others. At least in severe α1AT deficiency, any coexistence of the PiZZ phenotype and AAA would seem to be fortuitous.
Subacute cor pulmonale due to microscopic pulmonary tumour cell embolization
Authors: LAMBERT‐JENSEN P. , MERTZ H. , NYVAD O. , CHRISTENSEN J. HAGSTRUP
Published: August 2009

Abstract. A case of a clinically occult ovarian carcinoma leading to subacute cor pulmonale in a 62‐year‐old woman is described. The patient was admitted to hospital with increasing respiratory distress. Physical examination and echocardiography showed signs of pulmonary hypertension. She died from circulatory failure. Autopsy revealed a bilateral ovarian carcinoma with diffuse carcinosis of the peritoneum. No gross evidence of pulmonary embolism was present, but microscopic investigation revealed tumour‐related microangiopathic lesions causing the lethal pulmonary hypertension.
Homocyst(e)ine and arterial occlusive diseases
Authors: MALINOW M. R.
Published: August 2009

Abstract. Homocysteine is a thiol‐containing amino acid resulting from demethylation of methionine. The free and protein‐bound forms of the amino acid derived disulfides are called homocyst(e)ine [H(e)]. Multiple studies have shown elevated H(e) levels in patients with coronary, cerebrovascular, or peripheral arterial diseases; this association is frequent and independent of most other risk factors for atherosclerosis. In the 1993 Frontiers in Medicine Symposium* investigators discussed the genetic, physiological, nutritional, and pharmacological mechanisms involved in the regulation of plasma H(e), the association of H(e) with arterial occlusive diseases, and the relationships of H(e) with nitric oxide and haemostasis.

High plasma H(e) levels usually can be reversed with vitamin supplements. Whether vitamin supplements will affect the evolution of arterial occlusive diseases needs to be established in prospective, placebo‐controlled, randomized, clinical trials.
Corticosteroids and peptic ulcer: meta‐analysis of adverse events during steroid therapy
Authors: CONN H. O. , POYNARD T.
Published: August 2009

Abstract. Objectives. This meta‐analysis was performed to determine whether corticosteroid therapy induces the development of peptic ulcer and other putative complications of steroid therapy.

Design. A retrospective investigation in which we analysed all the randomized, double‐blind, controlled trials (RDBCT) in which steroids had been administered that we were able to identify. The number of episodes of peptic ulcer, dermatological effects, sepsis, diabetes, hypertension, osteoporosis, psychosis and tuberculosis reported in both the placebo and steroid groups were compared.

Setting. The international medical literature was analysed for any RDBCT in which any steroid or ACTH had been administered in any dosage for any duration, and any putative complication of steroid therapy was reported.

Subjects. Of 1857 articles, 93 satisfied our requirements and were analysed by the meta‐analytic techniques of Peto, DerSimonian and Laird. A total of 6602 patients were included.

Main outcome measures. The relative frequencies of each of these eight ‘complications’ were compared in the placebo and steroid groups using conventional statistics and meta‐analysis. The relative frequencies of ‘annualized’ subgroups of patients who received treatment for 1 to 7 days, 1 week to 1 month, 1 to 3 months and more than 3 months, were similarly analysed.

Results. Nine of 3267 patients in the placebo group (0.3%) and 13 of 3335 patients in the steroid group (0.4%) were reported to develop peptic ulcer (P < 0.05). The dermatological cosmetic effects of steroid therapy were observed more frequently in the steroid group (P < 0.001), as was diabetes (P < 0.001), hypertension (P < 0.001) and psychosis (P < 0.001). Sepsis, osteoporosis and tuberculosis all occurred more frequently in the steroid than in the placebo group, but the differences are not statistically significant.

Conclusions. Peptic ulcer is a rare complication of corticosteroid therapy that should not be considered a contraindication when steroid therapy is indicated.
Prognosis in therapy‐resistant hypertension
Authors: ISAKSSON H. , ÖSTERGREN J.
Published: August 2009

Abstract.Objectives.To study the prognosis in therapy‐resistant hypertension (RH).

Design.Patients with RH and age‐ and sex‐matched responding hypertensives, were followed‐up for a period of 7 years.

Setting.All subjects were outpatients at a secondary referral centre for hypertension.

Subjects.(i) Age ≤ 65 years; (ii) no prior diagnosis of secondary hypertension; (iii) on antihypertensive triple‐drug therapy of optimal dosage; (iv) diastolic blood pressure remaining 5 mmHg above their (age‐related) target pressure; (v) no history of renal failure, heart failure, stroke or myocardial infarction; and (vi) no record of noncompliance. A total of 800 patients were screened. Thirty‐six were finally included. For each study patient, two control patients were randomly selected.

Interventions.Continuous efforts to optimize blood pressure control were made in all patients.

Main outcome measures.Transient ischaemic attack or stroke, myocardial infarction, congestive heart failure, renal failure, and death. Development of non‐insulin‐dependent diabetes mellitus (NIDDM).

Results.At the end of the follow‐up period, RH had a casual functional blood pressure 21/6 mmHg higher than the control hypertensives. RH exhibited an increased incidence of stroke (P< 0.05), renal insufficiency (P< 0.05) and NIDDM (P< 0.05). RH patients had an increased risk of suffering an event during the 7 years [odds ratio (OR) 2.71;P< 0.05].

Conclusions.Resistance to antihypertensive therapy may persist even when therapy is aggressively applied in compliant patients. RH is associated to an increased risk of stroke and of target organ damage, foremost renal insufficiency. The apparent association between RH, obesity and NIDDM may imply that hyperinsulinaemia is involved in therapy resistance.
Factitious disorder presenting with acute cardiovascular symptoms
Authors: LUDWIGS U. , RUIZ H. , ISAKSSON H. , MATELL G.
Published: August 2009

Abstract. A 23‐year‐old female student exhibited all the characteristics of chronic factitious disorder with physical symptoms (Munchhausen's syndrome): deliberate simulation of illness, peregrination, fantastic pseudology and dramatic circumstances on admittance. The patient induced impressive blood pressure peaks by the Valsalva manoeuvre. She also simulated arrhythmias, seizures and unconsciousness. Her symptoms had previously led to comprehensive cardiological, neurological and endocrinological evaluations and treatment in at least three different countries in two continents. A literature survey suggests that factitious cardiovascular symptoms have become more frequent during recent decades.
Treatment preferences, return visit planning and factors affecting hypertension practice amongst general practitioners and internal medicine specialists (The General Practitioner Hypertension Practice Study)
Authors: RIBACKE MATS
Published: August 2009

Abstract. Objectives. To study clinical practice and attitudes in hypertension care amongst general practitioners (GPs) and hospital internal medicine specialists.

Design. Mailed case report questionnaires.

Subjects. Ninety GPs and 69 internal medicine specialists at randomly selected primary health care centres and hospital outpatient departments.

Main outcome measures. Case‐bound treatment preferences, treatment goals and return visit planning, and views on factors influencing practice.

Results. The participation rate was 84% and 70%, for GPs and internal medicine specialists, respectively. GPs more often proposed nonpharmacological therapy (P < 0.05), solely and as a complementary treatment, and prescribed more calcium antagonists (P < 0.001), whilst internal medicine specialists prescribed more ACE inhibitors (P < 0.001). Personal experience guides practice more than national consensus and economy, more so with increasing time since specialization.

Conclusions. GPs and internal medicine specialists in Sweden report a hypertension practice closely related to each others' and to the intentions of national guidelines.
Adverse effects of psychosocial stress on gonadal function and insulin levels in middle‐aged males
Authors: NILSSON PETER M. , MØLLER LARS , SOLSTAD KIM
Published: August 2009

Abstract.Objectives.To investigate the relationship between gonadal function, insulin and psychosocial stress in middle‐aged men.

Design.A population‐based, cross‐sectional, observational study.

Setting.Glostrup Hospital, Copenhagen, Denmark.

Subjects.Four hundred and thirty‐nine males, all aged 51 years.

Main variables.Body‐mass index (BMI), waist‐to‐hip ratio (WHR), insulin, C‐peptide, free testosterone, luteinizing hormone (LH), lipids, fibrinogen, lung function tests (FVC, FEV1, PEF), blood pressure; a self‐administered questionnaire with questions on psychosocial variables, lifestyle and self‐rated health.

Results.Free testosterone correlated inversely (P< 0.05) with weight, BMI, WHR, and fibrinogen, and positively withFEV1. An independent correlation between free testosterone and insulin (P≤ 0.03), but not with C‐peptide, was seen after controlling for BMI and WHR. Subjects with low levels of free testosterone, or those in the lowest quintile of the distribution of the hypogonadal index (HI: free testosterone/LH), showed a cluster of negative psychosocial variables, and psychological as well as health‐related problems. Furthermore, hypogonadal men had lower (P< 0.05) levels ofFEV1, peak flow andFVC, but higher (P< 0.01) levels of fibrinogen and higher pulse pressure than men with normal gonadal function. This gradient of variables, relative to HI, was not seen for possible confounders like BMI, WHR, and tobacco or alcohol consumption.

Conclusion.Psychosocial stress may be associated with a process of premature ageing in middle‐aged males, corresponding to a hypogonadal state as well as to indirect signs of increased insulin resistance.
Cold exposure increases cyclic guanosine monophosphate in healthy women but not in women with Raynaud's phenomenon
Authors: LEPPERT J. , RINGQVIST Å. , AHLNER J. , MYRDAL U. , SÖRENSEN S. , RINGQVIST I.
Published: August 2009

Abstract. Objective. To investigate influence of whole‐body cooling on cyclic GMP (cGMP) in women with Raynaud's phenomenon and in healthy women.

Design. The study was performed as an open, parallel‐group comparison between women with Raynaud's phenomenon and healthy women during the winter month of February.

Setting. The municipality of Västerås (Sweden).

Participants. The Raynaud group comprised 24 female patients. The control group consisted of 21 healthy females.

Main outcome measure. The venous levels of cGMP were measured on three different occasions: just before and after 40 min of whole‐body cooling and after 20 min rest at room temperature (21°C).

Results. Venous cGMP increased significantly in the control group after cold exposure (mean difference 0.43 pmol ml−1; 95% CI, 0.018–0.848; t = 2.18; df = 20; P = 0.02) and remained at a high level after 20 min rest (mean difference 0.58 pmol mL−1; 95% CI, 0.063–1.108; t = 2.34; df = 20; P = 0.015). In contrast, the levels of venous cGMP in the Raynaud group did not change significantly. The difference in increase between the two groups was significant (P < 0.02). The diastolic blood pressure in the Raynaud group increased after 40 min of whole‐body cooling and was still significantly increased (P < 0.001) after 20 min rest at room temperature (21 °C).

Conclusion. These results indicate that women suffering from Raynaud's phenomenon lack the physiological response of cGMP to cold exposure, which may explain their increased vasospastic response.
Chronic fatigue syndrome: a clinical and laboratory study with a well matched control group
Authors: SWANINK CAROLINE M. A. , VERCOULEN JAN H. M. M. , BLEIJENBERG GIJS , FENNIS JAN F. M. , GALAMA JOEP M. D. , VAN DER MEER JOS W. M.
Published: August 2009

Abstract. Objective. To investigate the relation between severity of complaints, laboratory data and psychological parameters in patients with chronic fatigue syndrome (CFS).

Subjects. Eighty‐eight patients with CFS and 77 healthy controls matched for age, sex and geographical area.

Methods. Patients and controls visited our outpatient clinic for a detailed medical history, physical examination and psychological tests: Checklist Individual Strength (CIS), Beck Depression Inventory (BDI) and Sickness Impact Profile (SIP). Venous blood was drawn for a complete blood cell count, serum chemistry panel, C‐reactive protein and serological tests on a panel of infectious agents.

Results. All patients fulfilled the criteria for CFS as described by Sharpe et al. (J R Soc Med 1991; 84: 118–21), only 18 patients (20.5%) fulfilled the CDC criteria. The outcome of serum chemistry tests and haematological tests were within the normal range. No significant differences were found in the outcome of serological tests. Compared to controls, significant differences were found in the results on the CIS, the BDI, and the SIP. These results varied with the number of complaints (CDC criteria). When the number of complaints was included as the covariate in the analysis, there were no significant differences on fatigue severity, depression, and functional impairment between patients who fulfilled the CDC criteria and patients who did not.

Conclusion. It is concluded that the psychological parameters of fatigue severity, depression and functional impairment are related to the clinical severity of the illness. Because the extensive panel of laboratory tests applied in this study did not discriminate between patients and controls, it was not possible to investigate a possible relation between the outcomes of psychological and laboratory testing.
von Willebrand factor, a possible indicator of endothelial cell damage, decreases during long‐term compliance with a lipid‐lowering diet
Authors: BLANN A. D. , JACKSON P. , BATH P. M. W. , WATTS G. F.
Published: August 2009

Abstract. Objectives. To test whether serum von Willebrand factor (vWf) would be lower in men with atherosclerosis who had been consuming a lipid‐lowering diet for 3 years than in a control group of men with atherosclerosis who had been following their normal diet.

Design. A randomized, population‐based case‐control study.

Setting. A tertiary health care referral centre at a University Hospital.

Subjects. Men age less than 66 years with angiographically proven coronary atherosclerosis and a cholesterol level > 6 mmol L−1. Sixty started the study and 50 completed it.

Interventions. Subjects were randomized to a lipid‐lowering diet or to taking their normal diet for approximately 3 years.

Main outcome measures. The components of the subjects' diets were assessed and blood was obtained for total, low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL) cholesterol, triglycerides and for vWf.

Results. Men on the lipid‐lowering diet consumed less total, saturated and monounsaturated fats (all P < 0.001), cholesterol and retinol (both P < 0.002) but increased polyunsaturated fats (P < 0.001), fibre, vitamin E (both P < 0.005) and carbohydrate (P < 0.05). Those on the lipid‐lowering diet also had lower serum levels of total and LDL cholesterol (P < 0.002 and P < 0.05, respectively), triglycerides (P < 0.02) and vWf (P < 0.05) than the men on their normal diet. There was no difference in HDL cholesterol. Levels of vWf correlated with both total cholesterol (P < 0.005) and inversely with dietary polyunsaturated fats (P < 0.02).

Conclusion. von Willebrand factor, a possible indicator of endothelial cell damage, decreases during long‐term compliance with a lipid‐lowering diet.
Liberalized diet in patients with type 1 diabetes
Authors: MÜHLHAUSER I. , BOTT U. , OVERMANN H. , WAGENER W. , BENDER R. , JÖRGENS V. , BERGER M.
Published: August 2009

Abstract.Objective.To document that strict dietary regimen are not necessary in the context of intensified insulin therapy.

Design.German multicentre, prospective cohort study; 6 years follow‐up.

Setting.Ambulatory examination using a mobile ambulance.

Subjects.A total of 636 type 1 diabetic patients (age 33 ± 7 years, diabetes duration 15 ± 7 years; mean ± SD), who had participated in a structured, 5‐day, in‐patient, group treatment and teaching programme for intensification of insulin therapy and liberalization of the diabetes diet 6 years prior to follow‐up.

Main outcome measures.Relations between the extent to which patients practise a liberalized diet, the degree of metabolic control (HbA1c, severe hypoglycaemia, body mass index, cholesterol), and the patients' perceived burden through dietary treatment.

Results.In the total patient group, HbA1c was 7.9 ± 1.6%, and the incidence of severe hypoglycaemia was 0.17 cases per patient during the preceding year; 31% patients injected insulin ≤ 3 times per day, 58% 4–7 times per day, and 11% used insulin pump therapy. Only 11% patients reported following a meal plan, whereas 89% continually changed timing and amount of carbohydrate intake; only 5% had the same number of meals every day, whereas as many as 20% varied the number of meals per day by four or more; 53% skipped main meals; 85% habitually consumed sugar or sugar containing foods. Patients with a higher degree of diet liberalization injected insulin or used an insulin pump therapy more frequently, and perceived their dietary treatment to be less burdensome. No clinically significant associations were found between the extent of diet liberalization and metabolic control.

Conclusions.Under the conditions where type 1 diabetic patients have the opportunity to participate in an intensified insulin treatment and teaching programme, liberalization of the diabetes diet is not associated with adverse effects on glycaemic control, but is associated with less perceived burden through dietary treatment.
Coronary heart disease in diabetes mellitus: three new risk factors and a unifying hypothesis
Authors: YUDKIN JOHN S.
Published: August 2009

Abstract. The standard risk factors ‐ dyslipidaemia, hypertension and smoking ‐ provide little help in explaining the raised cardiovascular risk in diabetes. It can be calculated that intervening for disturbances of these risk factors could do little to rectify the loss of life expectancy of around 10 years for a middle‐aged diabetic man. Three new risk factors are discussed, which together may contribute to some of the excess cardiovascular risk in diabetes. Plasminogen activator inhibitor is an inhibitor of fibrinolysis which is elevated in concentration in diabetic subjects, and may increase both the incidence of thrombotic events and the risk of reinfarction after the initial infarct. Recent work also suggests that high activity of this substance may impair pharmacological fibrinolysis. Proinsulin‐like molecules are elevated in concentration in diabetic patients and correlate with levels of a number of other risk factors. Whilst these correlations may represent cause and effect for plasminogen activator inhibitor, there is no evidence that changes in levels of proinsulin‐like molecules influence levels of other risk factors. Microalbuminuria provides a powerful indicator of cardiovascular risk in both diabetic and non‐diabetic subjects, but whilst the mechanisms for this association are unclear, they are again unlikely to be mediated through changes in levels of standard risk factors. Recent observations of an association between short stature and microalbuminuria suggest that intrauterine or early infant nutrition may represent a common antecedent, these having also been shown to predict both components of the insulin resistance syndrome and cardiovascular disease in adult life.
Structural cardiac changes in relation to 24‐h ambulatory blood pressure levels in borderline hypertension
Authors: LEMNE C. , LINDVALL K. , GEORGIADES A. , FREDRIKSON M. , de FAIRE U.
Published: August 2009

Abstract. Objectives. To investigate left ventricular hypertrophy (LVH) in relation to 24‐h ambulatory blood pressure (24‐ABPM) and insulin levels in borderline hypertension.

Design. A case‐control study.

Subjects. Borderline hypertensive men (diastolic blood pressure (DBP) 85–94 mmHg, n = 69) and age‐matched normotensive controls (DBP ≤ 80 mmHg. n = 69) from a population screening programme.

Main outcome measures. Echocardiography (M‐mode). insulin (RIA) and 24‐APBM (Del Mar P‐IV) levels.

Results. The borderline group showed a significant increase in septal thickness (10.4±1.5 vs. 9.7±1.5 mm. P < 0.01), peak systolic wall stress (218±38 vs. 202±38 103 dynes cm−2, P < 0.05) and a decrease in LV ejection time (28.4±2.5 vs. 29.5±2.1s, P < 0.01). The septum vs. posterior wall thickness ratio was significantly higher in the borderline group (1.13±0.14 vs. 1.06±0.14, P < 0.01). Casual BP levels did not correlate with LVH indices, while 24‐ABPM systolic levels correlated strongly with LVH indices in the borderline group (r = 0.22–0.52, P < 0.05) but not in the normotensive group. Insulin levels correlates strongly with LVH indices in the normotensive group (r = 0.34–0.47, P < 0.01) but not the borderline, group.

Conclusions. Signs of asymmetric LVH and altered ventricular function are already detectable in borderline hypertension. The data also suggest that early structural cardiac changes are related to ambulatory blood pressure profile, but not to casual blood pressure or trophic factors such as insulin.
Primary haemostasis in thyroid disease
Authors: MYRUP B. , BREGENGÅRD C. , FABER J.
Published: August 2009

Abstract. Objectives. There have been reports on a bleeding tendency in hypothyroidism resembling von Willebrand's disease. The aim of the present study was to investigate whether altered primary haemostasis is a general phenomenon in thyroid disease.

Design/setting. A total of 10 patients with hyperthyroidism and nine patients with hypothyroidism were studied at diagnosis, and during treatment with carbimazole or L‐thyroxine. respectively, when euthyroidism had been achieved.

Results. In untreated hypothyroidism, template bleeding time was prolonged (median 9.3 min, range 3.8–20.0 min) compared to that in controls (median 4.0 min, range 3.0–6.0 min; P < 0.05). whereas maximal agglutination velocity induced by ristocetin was decreased (38% min−1, range 4–52% min−1 vs. 70% min−1, range 60–81% min−1, P < 0.05). The level of von Willebrand factor antigen in plasma from hypothyroid patients was less than half of the value in hyperthyroid patients. This difference disappeared after euthyroidism was achieved.

Conclusions. We found that changed primary haemostasis is a general feature of hypothyroidism, and that it is resolved after levothyroxine treatment.
Sleep and hypnotics among the elderly in relation to body weight and somatic disease
Authors: ASPLUND R.
Published: August 2009

Abstract. Objectives. To investigate the interrelationship between sleep complaints and hypnotics in relation to general health and somatic diseases.

Design. An epidemiological survey conducted by means of a questionnaire.

Setting. The counties of Västerbotten and Norrbotten in northern Sweden.

Subjects. All 10216 members of the Swedish Pensioners' Association.

Main outcome measures. Sleep disturbances, health, somatic diseases and hypnotic medication.

Results. General ill health, cardiovascular diseases, different painful diseases and increased nocturnal voiding frequency were all associated with poor sleep and increased treatment with hypnotics. Hypnotics were used by 13.5% of the men and 22.3% of the women. Of the men aged < 70 years, 7.9% were receiving such treatment, of those aged 70–80 years 14.4% were using hypnotics, and of those aged ≥ 80 years 21.8% were taking hypnotics (P < 0.0001). The corresponding frequencies among women were 15.0%, 23.0% and 34.9%, respectively (P < 0.0001). Half of all men and women treated with hypnotics in all age groups reported a good night's sleep. Among these both angina pectoris and cardiac arrhythmia were twice as common as among elderly subjects who experienced poor sleep and were receiving treatment with hypnotics.

Conclusions. Poor health and different somatic diseases are over‐represented in elderly persons treated with hypnotics.
Hypertension in cyclosporin A‐treated patients is independent of circulating endothelin levels
Authors: FORSLUND T. , HANNONEN P. , REITAMO S. , FYHRQUIST F.
Published: August 2009

Abstract. Objectives. To measure blood pressure (BP), plasma endothelin‐1 (ET‐1), atrial natriuretic peptide (ANP), antidiuretic hormone (ADH) and aldosterone (ALDO) concentration, and plasma renin activity (PRA) in patients treated with a low‐dose cyclosporin A (CyA).

Design. An open study of patients with rheumatoid arthritis (RA) or palmoplantar pustulosis (PPP).

Setting. Out‐patient clinics at the Central Hospital of Jyväskylä and Helsinki University Central Hospital.

Subjects. CyA was given to 25 patients with RA and to 10 patients with PPP.

Intervention. RA patients were given CyA at a dose of 2.5±0.13 mg kg−1 body weight (BW) to 3.47±0.79 mg kg−1 BW (mean values±SD) at the start of the study and after 6 months, respectively, and the CyA dose was 2.67±0.13 mg kg−1 BW decreasing to 2.07±0.96 mg kg−1 (P < 0.001) after 4 months in PPP subjects.

Results. Systolic (sBP) and diastolic blood pressure (dBP) increased from 127.8±13.6/79.7±8.4 mmHg to 140.0±19.8/83.8±9.7 mmHg during the study (P < 0.03). Plasma ET‐1, ANP, ALDO and ADH concentration and PRA did not change during 4 to 6 months of CyA treatment. The plasma ANP concentration was constantly higher in CyA‐treated RA patients (112±87 ng l−1) to 118±78 ng l−1) than in PPP patients (37.3±26 ng l−1 to 47.7±39.9 ng l−1; P < 0.02). The serum creatinine concentration remained within the normal range, but increased from baseline (76.7±11.9 μmol l−1), to 90±15.4 μmol l−1 (P < 0.001). The serum magnesium concentration decreased significantly (P < 0.005) after 6 months of CyA treatment in RA patients. No correlation was found between serum creatinine and plasma ET‐1 concentration.

Conclusions. Increased blood pressure during CyA treatment was independent of circulating ET‐1 levels. A low dose of CyA did not induce increased ET‐1 synthesis as judged from plasma samples. The high plasma ANP level observed in RA patients could be due to fluid retention caused by concomitant treatment with non‐steroid anti‐inflammatory drugs. Fluid retention and decreased magnesium levels could also be involved in the development of hypertension in CyA‐treated subjects.
Acute adrenal insufficiency: A new presentation of Castleman's disease
Authors: CRUMP J. A. , BEARD M. E. J. , ANGUS H. B. , FRASER R. , HART D. N. J. , NICHOLLS M. G.
Published: August 2009

Abstract. We report the case of a 35‐year‐old patient who presented with acute adrenal insufficiency, then developed fever, hypoalbuminuria, anasarca, thrombocytopaenia and anaemia. Lymphadenopathy appeared later with microscopic features typical of Castleman's disease. Clinical remission followed treatment with intravenous immunoglobulin. Circulating interleukin‐6 levels were elevated initially but were normal after immunoglobulin therapy. We surmise that high circulating levels of interleukin‐6 (and ACTH) may have induced haemorrhagic necrosis of the adrenal glands and accounted for the constitutional symptoms.
Endotoxaemia and inflammatory mediators in febrile patients with haematological disease
Authors: GÜNTHER G. , GÅRDLUND B. , HAST R. , KIMBY E. , NORDIN M. , WRETLIND B.
Published: August 2009

Abstract. Objectives. To study the pattern of plasma levels of endotoxin, tumour necrosis factor alpha (TNF‐α), interleukin 6 (IL‐6) and C‐reactive protein (CRP) in febrile neutropenic patients and to assess the potential diagnostic value of these analyses.

Design. Consecutive prospective study.

Setting. Patients treated at the haematology ward at Danderyd Hospital, Sweden.

Subjects. Ninety‐four patients with fever and haematological disease entered the study (male/female: 59/35) with 176 febrile episodes.

Interventions. Blood samples were drawn at days 0, 1, 2 and 6 after onset of fever for analysis of, endotoxin, TNF‐α, IL‐6 and CRP.

Results. Infectious aetiology was established in 62.5% of the febrile episodes. Blood cultures showed significant growth in 71/176 (40.3%) febrile episodes. Nonbacteraemic bacterial infections were diagnosed in 34/176 (19.3%) episodes. Endotoxin was detected in plasma in 40% of febrile episodes regardless of aetiology. TNF‐α was detected in 61% and IL‐6 in 94% of all febrile episodes. The initial TNF‐α and IL‐6 levels were significantly higher in patients with Gram‐negative bacteraemia than in patients with other causes of fever (P < 0.001). In episodes evaluated as successful after empirical antibiotic treatment, a significant (P < 0.001) decrease in CRP concentrations were found on day 6 after onset of fever.

Conclusions. The sustained, low‐grade endotoxaemia and persistently elevated levels of TNF‐α and IL‐6 found in febrile patients may reflect a failing mucosal barrier that allows endogenous bacterial products to reach the circulation. The diagnostic value of endotoxin, TNF‐α, IL‐6 and CRP to discriminate between bacteraemic and nonbacteraemic febrile episodes was very limited. The study supports the present policy of broad, empirical antibiotic treatment in patients with haematological disease and fever.
High serum alpha‐tocopherol, albumin, selenium and cholesterol, and low mortality from coronary heart disease in northern Finland*
Authors: LUOMA P. V. , NÄYHÄ S. , SIKKILÄ K. , HASSI J.
Published: August 2009

Abstract. Objectives. The mortality from coronary heart disease (CHD) is exceptionally low in northernmost Finland, the Sámi (formerly known as Lapp) area. To clarify the reasons for this, the levels of serum cholesterol, other classic risk factors, and major antioxidants, alpha‐tocopherol, retinol, albumin and selenium were determined in males living in the low‐mortality area and in a reference area.

Design. A health survey amongst reindeer herdsmen living in the three northernmost communes of Finland (the Sámi area) and in the six neighbouring communities to the south (the reference area). The mortality from CHD in the two areas was determined from death certificates issued during the period 1981–1990.

Subjects. A total of 350 participants of the health survey, mean age 46 (SD 14) years.

Results. The mortality from CHD was 17% lower in the Sámi area than in the reference area [95% confidence interval (CI) for the difference: 4–29]. Subjects living in the low‐mortality area showed higher serum‐lipid‐adjusted alpha‐tocopherol (18.4 vs. 16.1 μmol L−1; 95% CI for difference: 0.7–3.9; P < 0.001), albumin (46.9 vs. 46.2 g L−1; 0.2–1.3; P < 0.02), selenium (1.59 vs. 1.47 μmol L−1; 0.02–0.22; P < 0.02), cholesterol (6.76 vs. 6.34 mmol L−1; 0.12–0.72; P < 0.001) and LDL cholesterol (4.76 vs. 4.45 mmol L−1; 0.05–0.57; P < 0.02) than those in the reference area. The HDL cholesterol: cholesterol ratio was lower in the Sámi area than in the reference area (0.20 vs. 0.21; –0.02–0.00; P < 0.04). The Sámis showed higher serum selenium than the Finns, Serum alpha‐tocopherol increased with the consumption of reindeer meat and serum selenium increased with fish consumption.

Conclusions. Alpha‐tocopherol, albumin and selenium may play a role in the low mortality from CHD observed in northernmost Finland. The favourable serum antioxidant status in northerners may be credited to the local diet.
Coffee consumption and risk of ischaemic heart disease — a settled issue?
Authors: GYNTELBERG F. , HEIN H. O. , SUADICANI P. , SØRENSEN H.
Published: August 2009

Abstract. Objective. Based on a meta‐analysis, it was recently stated that there is no association between coffee consumption and the risk of coronary heart disease. Why then, have studies on the issue shown quite variable results?

Design, setting and subjects. A prospective study was performed in the Copenhagen Male Study on 2975 men (53–74 years) without cardiovascular disease at the baseline in 1985/1986. They were classified according to self‐reported consumption of filter coffee. Some 147 men (5%) were coffee abstainers. Potential confounders were alcohol use, physical activity, smoking, serum cotinine, serum lipids, serum selenium, body mass index, blood pressure, Lewis blood group, hypertension, non‐insulin‐dependent diabetes mellitus and social class.

Main outcome measures. The incidence of ischaemic heart disease (IHD) 1985/86–1991.

Results. Some 184 men had a first IHD event. There was no significant difference between those consuming 1–4, 5–8 or ≥ 9 cups per day after controlling for confounders (P‐value of trend test: 0.14). The crude incidence rates were 6.8, 6.7 and 4.6%, respectively; the adjusted rates were 6.8, 6.7 and 4.0%, respectively. Coffee consumption was significantly (P < 0.05) inversely correlated with serum selenium concentration (never previously described) and, positively or negatively, with a number of other potential risk factors: smoking, alcohol use, serum triglycerides, serum cholesterol, blood pressure, social class, body mass index, and serum selenium. In nonsmokers and smokers of only a small amount of tobacco, coffee consumption was associated with a lower risk of IHD (P < 0.05).

Conclusion. We conclude that the association between coffee consumption and risk of IHD is conditioned by known risk factors correlated with use of coffee, which may partly explain the inconsistencies in the results of previous studies.
Contrasting effects of angiotensin converting inhibitor and alpha‐1‐antagonist on albuminuria in insulin‐dependent diabetes mellitus patients with nephropathy
Authors: HOLDAAS H. , HARTMANN A. , BERG K.J. , LANGBERG H. , BLYSTAD L. , FAUCHALD P.
Published: August 2009

Abstract. Objective. The main aim of this study was to examine the effects of an angiotensin converting inhibitor, enalapril, and an alpha‐1 (α‐1) antagonist, doxazosin, on albumin excretion, renal haemodynamics and tubular function in insulin‐dependent diabetes mellitus patients with nephropathy.

Design. The study consisted of a four‐week run‐in period, a four‐week active treatment period, a four‐week wash‐out period and a second four‐week active treatment period.

Setting. The study was performed in the out‐patient clinic at a university hospital.

Subjects. Ten patients with insulin dependent diabetes mellitus with macroalbuminuria (> 200 μg min−1), mild to moderate hypertension (diastolic blood pressure 85–115 mmHg) and serum creatinine level below 200 μmol L−1 were included in the study.

Main outcome measures. The effect of the drugs on albumin and total protein excretion, β‐2‐microglobulin, proximal tubular enzyme markers and renal haemodynamics.

Results. Systolic and diastolic blood pressure were equally reduced by both drugs. Enalapril reduced albumin excretion from 1090 ± 281 μg min−1 to 742 ± 246 μg min−1 (P < 0.01) and total protein excretion from 2.0 ± 0.4 g per 24 h to 1.3 ± 0.4 per 24 h whereas doxazosin was without effect. Glomerular filtration rate and effective renal plasma flow were unchanged by either drug. Doxazosin increased filtration fraction from 0.21 ± 0.02 to 0.23 ± 0.01 (P < 0.05). The urinary excretion of the proximal enzyme markers N‐acetyl‐beta‐glucosaminidase and alkaline phosphatase were elevated as well as urinary excretion of β‐2‐microglobulin. However, neither the excretion of β‐2‐microglobulin nor the enzyme markers were affected by either drug.

Conclusions. Enalapril, but not doxazosin, reduces albuminuria in insulin dependent diabetes mellitus patients with nephropathy. The drugs exert differential effects on renal haemodynamics.
Heart failure: a growing public health problem
Authors: ERIKSSON H.
Published: August 2009

Abstract. At a time when deaths from coronary heart disease and stroke are markedly declining, mortality from heart failure is increasing. Heart failure is a costly and devastating disease, and throughout much of the industrialized world, escalating health‐care costs constitute a serious burden on both public and private systems of financing health care, and about one‐third of all heart failure patients are admitted to hospital each year.

Both prevalence and incidence of heart failure increase steeply with increasing age. The prevalence rate is about 1% at the age of 50, whilst at the age of 80 and above, almost one out of 10 persons will suffer from heart failure. Until recently, the goals for heart failure treatment were to relieve symptoms and enhance functional capacity. Recently, some large scale studies have shown that ACE inhibitors can reduce mortality, prevent development of heart failure, avoid the need for hospitalization and improve prognosis. ACE inhibitors may therefore have promising effects both on patients and on society.

A challenge for the future must be early recognition and timely and adequate treatment of heart failure. Such a strategy might have great economic benefits as far as public health is concerned. However, the most rewarding efforts for the population will be to prevent the underlying causes of coronary heart failure as well as risk factors for heart failure.

This review will study the magnitude of heart failure as a growing public health problem, the underlying causes, risk factors and treatment.
The putative role of alpha‐1‐antitrypsin in the disaggregation of amyloid lambda fibrils
Authors: ERIKSSON S. , JANCIAUSKIENE S. , MERLINI G.
Published: August 2009

Abstract. Background and objectives. Interactions between hydrophobic compounds like cholesterol and lithocholic acid and alpha‐1‐antitrypsin (α‐1‐AT) have previously been described. We studied the putative interaction between α‐1‐AT and the insoluble, hydrophobic, β‐pleated sheet, light‐chain‐derived fibrils that predominate the tissue deposits in primary immunocytic (AL) related amyloidosis.

Subjects and methods. Amyloid fibrils were isolated from two cases with lambda and two cases with kappa AL amyloidosis.

Results. The lambda fibrils could be completely disaggregated (as shown by light and electron microscopy and Congo red uptake) by α‐1‐AT added in the molar ratio 1:5, whereas fibrils with predominantly kappa chains remained unaffected. The lambda‐chain interaction was accompanied by characteristic changes of the physicochemical and biological properties of α‐1‐AT apparent in an increased thermal stability and loss of elastase‐inhibitory activity. These findings are compatible with a transition of α‐1‐AT from a native, stressed conformation to a relaxed form.

Conclusions. Disaggregation of lambda AL amyloid fibrils can be achieved by addition of α‐1‐AT. The findings may have therapeutic implications in primary amyloidosis.