bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival in breast cancer patients after the first episode of hypercalcaemia
Authors: Kristensen  , Ejlertsen  , Mouridsen  , Loft
Published: March 2003

Kristensen B, Ejlertsen B, Mouridsen HT, Loft H (Copenhagen University Hospital, Copenhagen, Denmark). Survival in breast cancer patients after the first episode of hypercalcaemia. J Intern Med 1998; 244: 189–98.

Objectives

.To investigate hypercalcaemia (serum ionized calcium (S‐Ca2+) > 1.35 mmol L−1) in breast cancer patients before and after the introduction of bisphosphonates and the effect of disease‐ and treatment‐related factors on survival.

Design

.Prospective and retrospective registration of covariates.

Setting

.A department of oncology in a university hospital.

Subjects

.A consecutive cohort of 212 hypercalcaemic patients never treated with bisphosphonate was identified prospectively (period 1) and 193 patients with metastases were classified into three groups: mild (S‐Ca2+ < 1.48; n= 102), moderate (1.48 ≤ S‐Ca2+≤ 1.60; n= 41), and severe hypercalcaemia (S‐Ca2+ > 1.60 mmol L−1; n= 50). Fifty‐one patients with severe hypercalcaemia all treated with bisphosphonate except one were identified retrospectively (period 2).

Results

.For period 1 median survival was 6.7 months. Survival was significantly decreased in the two groups with the highest initial S‐Ca2+ (P < 0.0001). Median survival times in severely hypercalcaemic patients from periods 1 and 2 were 1.4 (95% confidence interval 0.8–2.1) and 2.2 (95% confidence interval 1.3–3.1) months, respectively. In a Cox model for period 1 significant covariates were: WHO performance, extent of metastases, whether systemic anticancer treatment could be given, and haemoglobin, but not S‐Ca2+.

Conclusion

.Prognosis is poor in hypercalcaemic breast cancer patients with WHO performance 3–4 and advanced metastatic disease when effective systemic treatment can no longer be offered. Bisphosphonate treatment does not seem to improve survival in severe hypercalcaemia. Antihypercalcaemic treatment of mild malignancy‐associated hypercalcaemia appears not to be vital. Therapeutic efforts should be aiming at patients with moderate hypercalcaemia.
Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity: distinct differences between patients with anti‐proteinase 3 and anti‐myeloperoxidase autoantibodies
Authors: Franssen  , Gans  , Kallenberg  , Hageluken  , Hoorntje
Published: March 2003

Franssen C, Gans R, Kallenberg C, Hageluken C, Hoorntje S (University Hospital, Groningen; Free University Hospital, Amsterdam; and Catharina Hospital, Eindhoven; the Netherlands). Disease spectrum of patients with antineutrophil cytoplasmic autoantibodies of defined specificity: distinct differences between patients with antiproteinase 3 and antimyeloperoxidase autoantibodies. J Intern Med 1998; 244: 209–16.

Objective

To compare the disease spectrum of consecutive patients with antineutrophil cytoplasmic autoantibodies directed against proteinase 3 (anti‐PR3) or myeloperoxidase (anti‐MPO).

Design

Retrospective analysis.

Setting

Three teaching hospitals in the Netherlands.

Main outcome measures

Clinical features at presentation, histopathological characteristics and outcome.

Subjects

All consecutive patients who tested positive for anti‐PR3 (n= 46) or anti‐MPO (n= 46) over an 8‐year‐period.

Results

At diagnosis, patients with anti‐PR3 had a higher vasculitis activity index than patients with anti‐MPO (P < 0.001). The mean (SD) number of affected organs in the anti‐PR3 group exceeded that of the anti‐MPO group (3.9 (1.4) and 2.2 (1.1), respectively; P < 0.01). The combination of renal and respiratory tract involvement was present in as many as 78.3% of patients with anti‐PR3 and in only 23.9% of patients with anti‐MPO (P < 0.01). Renal‐limited disease exclusively occurred in patients with anti‐MPO. Granulomas were found in 41.3% of anti‐PR3‐ but in only 4.3% of anti‐MPO‐positive patients (P < 0.01). All anti‐PR3‐positive patients had Wegener's granulomatosis or microscopic polyangiitis. By contrast, diagnoses in the anti‐MPO group were more diverse: idiopathic necrotizing crescentic glomerulonephritis (26.1%), microscopic polyangiitis (26.1%), Churg–Strauss syndrome (4.3%), Wegener's granulomatosis (2.2%), giant cell arteritis (2.2%), clinically suspected vasculitis (19.6%), as well as miscellaneous nonvasculitic disorders (19.6%). During follow‐up, 10 anti‐PR3‐positive patients had 11 relapses whereas only 3 patients with anti‐MPO relapsed (P= 0.04).

Conclusion

A large divergence was seen in the disease spectrum between patients with anti‐PR3 and those with anti‐MPO. In particular, extra‐renal disease manifestations, granuloma formation and relapses were more prominent in anti‐PR3‐ than in anti‐MPO‐positive patients.
Extrahepatic manifestations of chronic hepatitis C infection and the interrelationship between primary Sjögren's syndrome and hepatitis C in Swedish patients
Authors: Verbaan H. , Carlson J. , Eriksson S. , Larsson Å. , Liedholm R. , Manthorpe R. , Tabery H. , Widell A. , Lindgren S.
Published: March 2003

Objective. To analyse the frequency of some extrahepatic manifestations of chronic hepatitis C virus (HCV) infection in northern European patients, including a postulated association between HCV and primary Sjögren's syndrome (SS).

Design. Cohort study.

Setting. Department of Medicine, Malmö University Hospital, Sweden.

Patients. Twenty‐one patients with HCV infection and 53 with primary SS (according to the Copenhagen criteria).

Main outcome measures. Cryoglobulins were analysed in all patients, while patients with primary SS were investigated with regard to markers of HCV infection, and HCV patients with objective tests of SS (Schirmer‐1 test, break‐up time, van Bijsterveld score, sialometry, labial salivary gland biopsy) and antibodies against nuclear antigens, smooth muscle (SMA) and mitochondria (AMA). HCV antigens in small salivary glands from lower lip biopsies were detected by immunohistochemical analysis.

Results. Only one of the SS patients had detectable cryoprecipitates, while another was HCV‐positive. None of the 21 HCV patients had cryoprecipitates. A total of 14/21 (67%) patients with HCV infection had at least one abnormal objective test suggestive of xerostomia or keratoconjunctivitis sicca, while eight (38%) had objective evidence of both eye and salivary gland involvement. HCV antigens were not detected in affected glands. Only two patients had clinical symptoms of SS, and two fulfilled the Copenhagen criteria for SS. None of the HCV‐positive patients had detectable antibodies against SS‐A, SS‐B, RNP, Jo‐1, PCNA or Scl‐70, and the frequency of ANA/SMA/AMA was low.

Conclusions. While involvement of salivary and lacrimal glands was common in Swedish patients with HCV infection, cryoglobulinaemia was not observed. The pathogenetic mechanism responsible for glandular inflammation appears to be different from that in primary SS. HCV infection does not seem to be an aetiological factor for primary SS in this population. These observations suggest that viral, genetic or possibly environmental factors may be responsible for the reported high frequencies of systemic complications associated with chronic hepatitis C infection in southern Europe.
Low vitamin E status is a potential risk factor for insulin‐dependent diabetes mellitus
Authors: Knekt P. , Reunanen A. , Marniemi J. , Leino A. , Aromaa A.
Published: March 2003

Objectives. To study the association of vitamin E status with occurrence of insulin‐dependent diabetes mellitus (IDDM).

Design. A case–control study nested within a 21‐year follow‐up study.

Subjects. Nineteen incident IDDM patients with an average age of 28 years and three individually matched controls per patient.

Main outcome measure. Serum concentrations of alpha‐tocopherol.

Results. Serum alpha‐tocopherol concentration at the baseline examination was inversely associated with IDDM occurring 4–14 years later. The cholesterol‐adjusted relative risk of IDDM between the highest and lowest thirds of the vitamin concentration was 0.12 (95% confidence interval = 0.02– 0.85).

Conclusions. The finding corroborates the hypothesis of a protective effect of vitamin E against development of IDDM. Because of the relatively old age of the patients in the present population, further epidemiological studies on the topic are warranted.
Prevalence of the metabolic syndrome in drug‐treated hypertensive patients and control subjects
Authors: Rantala A. O. , Kauma H. , Lilja M. , Savolainen M. J. , Reunanen A. , Kesäniemi Y. A.
Published: March 2003

Objectives. To determine the prevalence of the metabolic abnormalities associated with hypertension and to define the predictors of the metabolic syndrome by different definitions in random population‐based samples.

Design. A cross‐sectional epidemiological study of hypertensive patients and controls.

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

Subjects. Six hundred treated male and female hypertensives aged 40–59 years and 600 age‐ and sex‐matched controls were randomly selected by age stratification from population registers.

Main outcome measures. A wide range of laboratory analyses were conducted. After fasting blood had been drawn, the subjects were given a 75 g glucose load except previously known insulin‐treated diabetics. Both 1 h and 2 h glucose and insulin concentrations were determined. During the same visit, a standardized health questionnaire covering the past medical history, current and former medication use, physical activity, smoking habits, alcohol consumption and family history was completed. Ten different definitions of the metabolic syndrome were applied to achieve a wide perspective of the prevalence of the different combinations.

Results. The prevalence of the metabolic syndrome in different samples varied depending on the definition from 0.8 to 35.3%, being lowest in the control men and women and highest in the hypertensive men. Three‐quarters of a random, middle‐aged, urban population show at least one cardiovascular risk factor and 91.3% of all the hypertensive subjects show at least one cardiovascular risk factor in addition to hypertension itself. The independent predictors of the metabolic syndrome were waist circumference, uric acid, total cholesterol and gamma‐glutamyl transpeptidase in logistic analysis after adjustment for age, measure of obesity and gender.

Conclusions. This cross‐sectional, epidemiological study shows that the magnitude of the prevalence rates of the metabolic syndrome is at the same level in various populations, being less than one‐third in population‐based samples in spite of the different definitions. The cluster of several cardiovascular risk factors, especially in the hypertensives, leads to an increased relative risk of cardiovascular diseases.
Panic disorder in chest pain patients referred for cardiological outpatient investigation
Authors: Dammen T. , Arnesen H. , Ekeberg Ø. , Husebye T. , Friis S.
Published: March 2003

Objectives. The aims of the study were to: (i) determine the prevalence of panic disorder (PD) in patients referred to cardiological outpatient clinics for evaluation of chest pain; (ii) compare psychiatric comorbidity, psychological distress, pain characteristics and suicidal ideation in PD and non‐PD patients; (iii) compare the prevalence of coronary risk factors and medical comorbidity in PD and non‐PD patients; and (iv) describe current PD treatment and need for PD treatment as expressed by PD patients.

Design. A cross‐sectional study based on psychiatric and cardiological investigation.

Setting. Four cardiological outpatient clinics in Oslo, Norway.

Subjects. One‐hundred and ninety‐nine consecutive patients without known heart disease referred to outpatient clinics for investigation of chest pain.

Main outcome measures. Psychiatric state diagnosis (axis I); scores on self‐assessment rating scales of psychological factors and pain modalities; cardiological diagnosis.

Results. Thirty‐eight per cent of the patients met criteria for current panic disorder (PD). Panic disorder was associated with psychological distress, comorbid psychiatric disorders, medical disorders and significantly higher prevalence of coronary risk factors (P < 0.05). Furthermore, the results suggest that these patients were not identified and appropriately treated for panic disorder prior to cardiological investigation. The results indicate that the patients are positive to screening for psychiatric disorder and communicate a need for treatment early in the investigation process.

Conclusion. PD commonly occurs in this chest pain population. Thus, there is a need to educate physicians caring for these patients about PD identification and treatment.
Clinical importance of coronary endothelial vasodilator dysfunction and therapeutic options
Authors: B. Britten M. , M. Zeiher A. , Schächinger V.
Published: March 2003

The vascular endothelium plays a key role in the control of vasomotor tone, local haemostasis and vascular wall proliferation processes. These responses are mediated by a variety of substances released from the endothelium in response to physiological stimuli, including prostacyclin, endothelin, and most importantly nitric oxide (NO). NO mediates vasodilation and furthermore inhibits platelet aggregation, expression of adhesion molecules for monocytes and adhesion of neutrophils, and it impairs growth of vascular smooth muscle cells. Risk factors for coronary atherosclerosis, such as hypercholesterolaemia, impair NO bioactivity, mainly due to an oxidative stress by superoxide radicals (O2−), which are able of rapidly inactivating endothelium‐derived NO. Impaired NO bioactivity leads to unopposed paradoxical vasoconstriction of epicardial conductance vessels in response to physiological stimuli such as sympathetic activation as well as impaired vasodilator function of coronary resistance vessels. Therefore, endothelial dysfunction contributes to ischaemic manifestation of coronary artery disease. In addition, enhanced paradoxical vasoconstriction and a loss of endothelial antithrombotic activities might unfavourably modulate the course of acute coronary syndromes. Thus, the aim of therapeutic interventions is to increase NO bioavailability by either increasing NO production or decreasing O2− production in the endothelium. This goal can be reached, for example by ACE inhibitors, lipid‐lowering drugs, increased shear‐stress by physical exercise, oestrogens, and l‐arginine, which have already been shown to improve endothelial vasodilator function. Nevertheless, it has to be determined whether ameliorated endothelial function will contribute to improved patients prognosis.
Oral anticoagulants are effective long term after acute myocardial infarction
Authors: Smith P.
Published: March 2003

Three long‐term studies on oral anticoagulation, the Sixty Plus trial, the WARIS study, and the ASPECT trial all meet the methodological requirements for modern stand alone clinical trials: large number of patients, double‐blinded, placebo‐controlled design, and intention to treat analysis. All demonstrate significant reduction in recurrent myocardial infarction, and all show reduction in the risk of total stroke. The WARIS study, however, is the only study demonstrating efficacy in terms of statistically significant reduction of all‐cause mortality. These findings are confirmed by a recent meta‐analysis. The overall benefit of oral anticoagulation after myocardial infarction suggests avoidance of 4–26 events per 100 patients treated for 2–3 years. Given the results from the trials applying the most adequate control of anticoagulation, avoidance of 10–14 events per 100 patients treated seems to be a realistic benefit. Provided there is sound management of the anticoagulant therapy, especially employment of suitable control methods, the incidence of bleeding may be kept at a low level.
Life‐threatening ventricular tachycardia due to liquorice‐induced hypokalaemia
Authors: Eriksson J. W. , Carlberg B. , Hillörn V.
Published: March 2003

Abstract. Eriksson JW, Carlberg B, Hillörn V (Umeå University Hospital, Umeå, Sweden). Life‐threatening ventricular tachycardia due to liquorice‐induced hypokalaemia (Case Report). J Intern Med 1999; 245: 307–10.

We report on a patient with hypokalaemia and severe ventricular tachycardia of torsades de pointes type which turned out to be caused by an apparent mineralocorticoid excess syndrome associated with liquorice consumption. The patient, a 44‐year‐old woman, attended the hospital because of irregular heart rhythm and she displayed repeated episodes of life‐threatening torsades de pointes ventricular tachycardia. The initial serum potassium was low: 2.3 mmol L–1. The patient was treated with potassium and magnesium infusions, and the dysrhythmias eventually ceased. Endocrinological investigations showed no indication of Cushing’s syndrome or hyperaldosteronism. After some time it became clear that the patient had ingested moderately large amounts of liquorice every day for 4 months. After the patient stopped this habit the hypokalaemia and dysrhythmias did not recur and after more than 1 year there are no signs of cardiac illness.
Impaired granulocyte formylpeptide‐induced superoxide generation in chronically ill, malnourished, elderly patients
Authors: Cederholm T. , Gyllenhammar H.
Published: March 2003

Abstract. Cederholm T, Gyllenhammar H (Huddinge University Hospital, Huddinge, Sweden). Impaired granulocyte formylpeptide‐induced superoxide generation in chronically ill, malnourished, elderly patients. J Intern Med 1999; 245: 475–482.

Objective. Protein‐energy malnutrition (PEM), often occurring in patients with chronic disease, is associated with a decreased capacity to combat infections. In this study we assessed polymorphonuclear neutrophil (PMN) superoxide anion (·O2–) formation in elderly PEM patients with various chronic diseases.

Design and subjects. Nineteen patients (75 ± 1 years), with body mass index 17.1 ± 0.4, and 19 age‐matched healthy controls were included. Fourteen patients and 14 controls were re‐examined in a 3 month follow‐up.

Setting. A service of internal medicine at a university‐affiliated hospital.

Interventions. Eight patients were prescribed a dietary liquid supplementation during the observation period.

Main outcome measures. Superoxide production in PMN induced by fMLP (a receptor ligand) and phorbol myristate acetate (PMA), which acts directly on protein kinase C.

Results. fMLP‐induced superoxide generation in the malnourished patients was 55 ± 5% of that of the controls. However, the patients retained their capacity, 108 ± 6% of control PMN generation, to respond to PMA. In those who received formula supplementation, fMLP‐generated ·O2– production levels were 48 ± 8 and 73 ± 13% (P = 0.12) of those of controls at the start and after 3 months, respectively. Corresponding figures in those who were not prescribed supplementation were 57 ± 8 and 64 ± 4% (P = 0.55).

Conclusion. Possibly contributing to reduced host defence, receptor ligand‐induced PMN generation of ·O2– is significantly lower in chronically ill, elderly patients with PEM than in age‐matched healthy controls.
Lean mass and physical activity as predictors of bone mineral density in 16–20‐year old women
Authors: Valdimarsson Ö. , Kristinsson J. Ö. , Stefansson S. Ö. , Valdimarsson S. , Sigurdsson G.
Published: March 2003

Abstract. Valdimarsson Ö, Kristinsson JÖ, Stefansson SÖ, Valdimarsson S, Sigurdsson G (Reykjavik Hospital, University of Iceland, Reykjavik, Iceland). Lean mass and physical activity as predictors of bone mineral density in 16–20‐year old women. J Intern Med;245: 489–496.

Objective.  The aim of the study was to quantify the inter‐relationship between bone mineral density and physical activity, muscle strength, and body mass composition in a group of healthy 16–20‐year‐old women.

Design. A cross‐sectional study.

Setting.  Reykjavik area.

Subjects.  Two‐hundred and fifty‐four Icelandic Caucasian women aged 16, 18 and 20 years, randomly selected from the registry of Reykjavik.

Main outcome measures.  Bone mineral content (BMC) and density (BMD) in lumbar spine, hip, distal forearm and total skeleton and lean mass and fat mass were measured with dual energy X‐ray absorptiometry (DEXA) and compared with grip strength measured with a dynamometer and physical activity as assessed by a questionnaire.

Results.  The lean mass had the strongest correlation with BMC and BMD, stronger than weight, height and fat mass, both in univariate analysis (r = 0.41–0.77; P < 0.001) and in linear regression analysis. The total skeletal BMD was logarithmically higher by hours of exercise per week (P < 0.001)). About 30% of variability in total skeletal BMD in this age group can be predicted by lean mass and physical exercise.

Conclusions.  Modifiable factors, such as exercise and adequate muscle seem to be significant predictors of the attainment of peak bone mass in women.
Oral clodronate in breast cancer patients with bone metastases: a randomized study
Authors: Kristensen B. , Ejlertsen B. , Groenvold M. , Hein S. , Loft H. , Mouridsen H. T.
Published: March 2003

Objectives. To investigate the effect of the bisphosphonate clodronate on the occurrence of skeletal events (hypercalcaemia, fractures and radiotherapy) in breast cancer patients with bone metastases.

Design. Prospective, randomized, controlled, clinical trial.

Setting. A department of oncology in a university hospital.

Subjects. One hundred patients who received first‐line systemic antineoplastic treatment for metastatic breast cancer with bone involvement were randomized to receive clodronate as two 400 mg capsules twice a day for 2 years or no additional therapy.

Results. In the clodronate group the number of skeletal events was reduced to 14 events in 48 evaluable patients as compared with 21 events in 51 evaluable control patients. The time to the first skeletal event was significantly longer in the clodronate group than in the control group (P = 0.015) and the most distinct difference was a lower occurrence of fractures in the clodronate group (P = 0.023). After 15 months the effect of clodronate tended to decline as the need for radiotherapy increased in the clodronate group compared with the control group (P = 0.069). Significant improvements in several quality‐of‐life aspects were seen in both groups during the first 6 months, but there was no significant difference between the groups. No effect was observed on time to radiologically evaluated disease progression in bone or on survival. The most frequent side‐effects resulting in discontinuation of clodronate were nausea and diarrhoea.

Conclusion. Oral clodronate is associated with a temporary reduction of morbidity related to bone metastases in breast cancer patients.
Hereditary paraganglioma
Authors: Lemaire M. , Persu A. , Hainaut PH. , De Plaen J. F.
Published: March 2003

Head and neck paraganglioma is a rare tumour, especially in its familial form. We report a case of a multifocal head and neck paraganglioma in a young man with a family history of cervical tumours. At the age of 24, exploration of a left cervical swelling disclosed jugulotympanic and carotid body paragangliomas. Surgical removal of both tumours was performed. Two years later, a right carotid body as well as vagal paragangliomas were discovered. Follow‐up at age 30 demonstrated relapse of the bilateral cervical paragangliomas, but also aortopulmonary and mesogastric paragangliomas. Cervical paragangliomas were also detected in the patient’s sister and daughter, but not in his father. Furthermore, the proband’s paternal grandmother and a maternal great‐uncle had a history of ‘neck scar’. This family history is suggestive of an autosomal dominant pattern of inheritance with maternal genomic imprinting. Genetic analysis of paraganglioma kindreds showed linkage with two different loci: 11q13.1 and 11q22.3–q23. Further knowledge of the genes involved could provide early diagnosis and accurate genetic counselling in affected families. Thorough familial investigation is consequently mandatory in all head and neck paragangliomas, especially in younger patients with multiple localizations, as surgical removal is safer at an early stage.
Insulin sensitivity and haemostatic factors in men at high and low cardiovascular risk
Authors: Agewall S.
Published: March 2003

Abstract. Agewall S (Sahlgrenska University Hospital, Göteborg University, Sweden). Insulin sensitivity and haemostatic factors in men at high and low cardiovascular risk. J Intern Med 1999; 246: 489–495.

Objective. To investigate the relationship between variables of the coagulation and fibrinolysis system and insulin sensitivity in non‐diabetic men at high and low risk of cardiovascular disease.

Design. Cross‐sectional study.

Setting. Outpatient clinic in city hospital.

Patients. Thirty‐five men at high risk for atherosclerotic disease (hypertension and at least one the following factors: hypercholesterolaemia and smoking) and an age‐matched low‐risk group (n = 23) with no cardiovascular risk factors.

Main outcome measures. Insulin‐mediated glucose disposal (hyperinsulinaemic euglycaemic clamp) adjusted for lean body mass and fibrinogen, von Willebrand factor, prothrombin fragment 1 + 2, thrombin/antithrombin complex and plasminogen activator inhibitor activity were determined.

Results. Insulin‐mediated glucose disposal adjusted for lean body mass was significantly lower in the high‐risk group than in the low‐risk group. Glucose disposal was significantly negatively associated with plasminogen activator inhibitor activity (PAI) in the high‐risk group and with von Willebrand factor in the low‐risk group. In the whole study group, fibrinogen and PAI were significantly associated with glucose disposal. After adjusting for confounding factors, glucose disposal was independently negatively associated with PAI in the high‐risk group (P < 0.001) and in the whole group (P < 0.001).

Conclusions. High‐risk men were significantly more insulin‐resistant than the low‐risk group. Glucose disposal adjusted for lean body mass was associated with an impaired fibrinolytic activity in the high‐risk group. Fibrinogen was associated with insulin resistance in the whole study group. The negative relationship between von Willebrand factor levels and glucose disposal in the low‐risk group may indicate that insulin resistance can induce an endothelial dysfunction even in non‐diabetic subjects.
Clinical assessment of suspected deep vein thrombosis: comparison between a score and empirical assessment
Authors: Miron M.‐J. , Perrier A. , Bounameaux H.
Published: March 2003

Abstract. Miron M‐J, Perrier A, Bounameaux H (Division of Angiology and Hemostasis, and Medical Clinic 1, Department of Internal Medicine, Geneva University Hospital, Geneva, Switzerland). Clinical assessment of suspected deep vein thrombosis: comparison between a score and empirical assessment. J Intern Med 2000; 247: 249–254.

Objectives. To assess the accuracy and agreement of two methods of clinical evaluation: a formal score based on a number of items of fixed value (the so‐called Wells’ score), and an empirical assessment based on a predefined list of items that can be weighted individually. Clinical probability is essential to manage suspected deep vein thrombosis (DVT) and should be assessed before any diagnostic test.

Design. An open, nonrandomised, one‐centre study.

Setting. One centre in Switzerland (a university hospital delivering primary‐tertiary care).

Subjects. Two hundred and seventy outpatients with a prevalence of DVT of 21.1% (final diagnosis), out of an initial population of 328 patients, of which 52 had to be excluded because of a history of DVT (score not applicable) or because of insufficient clinical information (n = 6).

Results. Agreement between the two assessment tools was poor (kappa value of 0.32), but accuracy was excellent, with a prevalence of DVT of 1.3%, 18.1%, and 100% (empirical assessment), and 3.2%, 19.4%, and 73.9% (Wells’ score), for a low, intermediate or high clinical probability estimate, respectively. The main differences between the two methods were that (i) the empirical method performed slightly better in categorizing patients in the high probability class, and (ii) Wells’ score categorized more patients in the low probability class. When applied to two validated diagnostic strategies, the empirical assessment required slightly fewer phlebograms in both strategies, and Wells’ score required fewer repeat ultrasonograms (in the strategy that requires this procedure).

Conclusions. Clinical probability assessment can be done with a similar accuracy either empirically or using a score. Institutions should incorporate clinical probability assessment with either method depending upon their diagnostic strategy for suspected DVT.
Independent effects of obesity and cortisol in predicting cardiovascular risk factors in men and women
Authors: Walker B. R. , Soderberg S. , Lindahl B. , Olsson T.
Published: March 2003

Abstract. Walker BR, Soderberg S, Lindahl B, Olsson T (University of Edinburgh, Western General Hospital, Edinburgh, UK and the University of Umea, University Hospital, Umea, Sweden). Independent effects of obesity and cortisol in predicting cardiovascular risk factors in men and women. J Intern Med 2000; 247: 198–204.

Objectives. Recent data suggest that higher plasma cortisol may be associated with hypertension and insulin resistance in otherwise healthy men, as it is in Cushing’s syndrome. However, obesity in women is associated with lower plasma cortisol concentrations. This study sought to establish whether plasma cortisol is associated with cardiovascular risk factors in women as it is in men, and whether these relationships in either sex are confounded by obesity.

Design. A population‐based cross‐sectional study.

Setting. The MONICA study in northern Sweden.

Subjects. From a target cohort of 2500, 1921 subjects took part and 226 were randomly selected because they attended between 07.00 and 09.00 h after an overnight fast. A 75 g oral glucose tolerance test was performed and blood sampled at baseline and 2 h after glucose.

Results. Plasma cortisol was lower in relatively obese subjects: in men, this was observed only in the 2 h sample (r = –0.23, P = 0.02) and in women only in the fasting sample (r = –0.26, P < 0.01). Simple regression analysis did not identify relationships between plasma cortisol and blood pressure, serum lipids, fasting insulin or glucose tolerance. However, after adjusting for the effect of obesity by multiple regression, higher plasma cortisol was independently associated with higher diastolic blood pressure in men (r = 0.21, P = 0.04) but not in women, and higher fasting serum triglyceride levels in women (r = 0.28, P < 0.001) but not in men.

Conclusions. Increasing obesity and plasma cortisol concentrations make independent and sex‐specific contributions to variations in blood pressure and aspects of the insulin resistance syndrome. Adverse cardiovascular risk is greatest in those with the combination of obesity and failure to downregulate plasma cortisol levels.
Advanced glycation end product in familial amyloidotic polyneuropathy (FAP)
Authors: Nyhlin N. , Ando Y. , Nagai R. , Suhr O. , El Sahly M. , Terazaki H. , Yamashita T. , Ando M. , Horiuchi S.
Published: March 2003

Abstract. Nyhlin N, Ando Y, Nagai R, Suhr O, El Sahly M, Terazaki H, Yamashita T, Ando M, Horiuchi S (Umeå University Hospital, Umeå, Sweden and Kumamoto University School of Medicine, Kumamoto, Japan). Advanced glycation end product in familial amyloidotic polyneuropathy (FAP). J Intern Med 2000; 247: 485–492.

Objectives. Advanced glycation end products (AGE) are present in amyloid deposits in β2‐microglobulin amyloidosis, and it has been postulated that glycation of β2‐microglobulin may be involved in fibril formation. The aim of this paper was to ascertain whether AGE occur in amyloid deposits in familial amyloidotic polyneuropathy (FAP).

Setting. Department of Medicine, Umeå University Hospital and First Department of Internal Medicine, Kumamoto University School of Medicine.

Design. The presence of AGE was sought immunohistochemically and biochemically in amyloid‐rich tissues from patients with FAP.

Subjects. Biopsy specimens from nine patients and 10 controls were used for the immunohistochemical analysis. For amyloid preparation, vitreous samples from three FAP patients were used.

Results. Immunohistochemical studies using a polyclonal anti‐AGE antibody revealed positive immunoreactivity in intestinal materials, but the pattern of reactivity was unevenly distributed; it was often present in the border of amyloid deposits, or surrounding them. Non‐amyloid associated immunoreactivity was also observed in a few regions of the specimens, although the AGE‐positive structures were situated in areas containing amyloid deposits. Western blotting of purified amyloid from the vitreous body of FAP patients revealed a significant association of AGE with amyloid fibrils.

Conclusion. The immunoreactivity for the AGE antibody suggests that AGE may be involved in fibril formation in FAP.
The common pentanucleotide polymorphism of the 3′‐untranslated region of the leptin receptor gene is associated with serum insulin levels and the risk of type 2 diabetes in non‐diabetic men: a prospective case–control study
Authors: Lakka H.‐M. , Oksanen L. , Tuomainen T.‐P. , Kontula K. , Salonen J. T.
Published: March 2003

Abstract. Lakka H‐M, Oksanen L, Tuomainen T‐P, Kontula K, Salonen JT (University of Kuopio, Kuopio, and the University of Helsinki, Helsinki, Finland). The common pentanucleotide polymorphism of the 3′‐untranslated region of the leptin receptor gene is associated with serum insulin levels and the risk of type 2 diabetes in non‐diabetic men: a prospective case–control study. J Intern Med 2000; 248: 77–83.

Objectives. The purpose of the study was to test whether the pentanucleotide insertion/deletion polymorphism in the 3′‐untranslated region (3′‐UTR) of the leptin receptor gene, which has previously been associated with serum insulin levels in obese subjects, is associated with insulin levels and the risk of type 2 diabetes in non‐diabetic middle‐aged men.

Subjects and design. We studied these associations in a prospective population‐based nested case–control study in 41 men who developed type 2 diabetes during 4‐year follow‐up and 81 controls who were matched for age, obesity, baseline glucose and insulin and other strongest risk factors. Both the cases and the controls came from a cohort of 985 men who had no diabetes at baseline.

Results. There was one homozygote and 22 heterozygotes for the 3′‐UTR insertion allele amongst all 122 men. The carrier frequency of this allele was 9.8% amongst the cases and 23.5% amongst the controls. At baseline, the mean fasting serum insulin was 12.2 mU L–1 in the 23 men who were heterozygous or homozygous for the insertion allele and 17.1 mU L–1 in the 99 men who were homozygous for the deletion allele (P = 0.005). In a logistic regression model adjusting for four strongest non‐matched predictors of type 2 diabetes, the carriers of the insertion allele had a 79% reduced risk of diabetes (OR = 0.21; 95% CI = 0.06–0.77, P = 0.019), compared with non‐carriers.

Conclusion. Our findings support the hypothesis that alterations in the leptin signalling system could contribute to serum insulin levels and the development of type 2 diabetes.
Postmenopausal hormone therapy: less favourable risk–benefit ratios in healthy Dutch women
Authors: Moerman C. J. , Van Hout B. A. , Bonneux L. , Witteman J. C. M.
Published: March 2003

Abstract. Moerman CJ, van Hout BA, Bonneux L, Witteman JCM (University of Amsterdam, Amsterdam, and Erasmus University Medical School, Rotterdam, the Netherlands). Postmenopausal hormone therapy: less favourable risk–benefit ratios in healthy Dutch women. J Intern Med 2000; 248: 143–150.

Objectives. To estimate the health effects of postmenopausal hormone therapy used for 10 or 20 years in a population of intermediate cardiovascular risk.

Design. Using existing estimates of the effect of hormone therapy on rates of myocardial infarction, hip fracture and breast cancer, a proportional multistage life table was generated to calculate the effects of use for 10 and 20 years in a synthetic cohort of Dutch women aged 55 with an average and a high‐risk profile for cardiovascular disease.

Results. A woman of the general population who starts hormone therapy at age 55 for 10 years can prolong her life by 1 month and may postpone the occurrence of first incidence of one of the diseases under consideration by 2.4 months. One excess breast cancer case is likely to occur per 5–6 averted cases of first myocardial infarction or hip fracture. If she prolongs her use to 20 years, the gain of life expectancy and disease‐free life expectancy is doubled. The risk–benefit ratio worsens to one extra breast cancer per 3–4 averted cases of the preventable diseases. For a woman with a high‐risk profile, the gains in health are about twice as high as for her counterpart in the general population, and her risk–benefit ratio is also more favourable. Yet, the risk–benefit ratio still worsens for 20 as compared with 10 years of use.

Conclusions. Women from the general population in the Netherlands and similar populations can achieve only a modest gain in life expectancy by using hormones during 10 or 20 years following menopause. This is a consequence of the low incidence of myocardial infarction and hip fracture and the relatively high incidence of breast cancer before the age of 75. Women at increased cardiovascular risk can benefit more from hormone therapy. But even amongst these women, the risk of breast cancer incurred with long‐term use offsets much of the benefit that could accrue from changing the risk of heart disease and hip fracture.
Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT)
Authors: Kjeldsen A. D. , Oxhøj H. , Andersen P. E. , Green A. , Vase P.
Published: March 2003

Abstract. Kjeldsen AD, Oxhøj H, Andersen PE, Green A, Vase P (Odense University and Odense University Hospital, Odense; University of Aarhus, Aarhus; and the Department of Otorhinolaryngology, Svendborg, Denmark). Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT). J Intern Med 2000; 248: 255–262.

Background. Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease. HHT is characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs) and neurological symptoms.

Objective. To estimate (i) the prevalence of PAVM, and (ii) the occurrence of neurological symptoms in a geographical well‐defined population of HHT patients.

Methods. HHT family members were invited to a clinical examination including registration of HHT manifestations, screening for pulmonary arteriovenous malformations and neurological evaluation. Two groups served as controls: (i) first‐degree relatives without any signs of HHT; and (ii) age‐ and gender‐matched controls.

Setting. Odense University Hospital.

Subjects. HHT patients identified in a cross‐sectional family survey carried out in the County of Fyn, Denmark.

Results. Included in the study were 169 HHT family members representing 24 families. They included both HHT patients and their first‐degree relatives. The criteria of HHT were fulfilled in 75 participants; of these, 59 had a screening procedure performed, and PAVMs were demonstrated at pulmonary angiography (PA) in 18. Seven of the HHT patients had a history of cerebral stroke, compared with none of their healthy first‐degree relatives.

Conclusion. The prevalence of PAVM was 24% amongst HHT patients. The study confirmed an increased prevalence of neurological symptoms amongst HHT patients; the odds ratio was estimated to be 7.6. In order to enable prevention of these complications, screening for PAVM should become an integral part of the medical care for HHT patients.
Toxin‐mediated haemolytic uraemic syndrome without diarrhoea
Authors: Kater A. P. , Westermann A. M. , De Groot M. R. , Von Dem Borne A. E. G. KR. , Kuijper E. J.
Published: March 2003

Abstract. Kater AP, Westermann AM, de Groot MR, von dem Borne AEGKr (Academic Medical Centre, Amsterdam, The Netherlands). Toxin‐mediated haemolytic uraemic syndrome without diarrhoea (Case Report). J Intern Med 2000; 248: 263–265.

A 52‐year‐old previously healthy man was admitted to the hospital with haematuria, painful micturition and fever. Laboratory investigation showed the presence of a haemolytic uraemic syndrome (HUS), characterized by haemolysis, renal insufficiency and mental disturbances. A urinary tract infection caused by a verotoxin‐producing E. coli other than O157:H7 was diagnosed. Treatment of this infection resulted in his complete recovery from the illness. Both the search for a focus outside the gastrointestinal tract and the search for verotoxin genes by specific polymerase chain reaction can be crucial in a patient with HUS without preceding diarrhoea.
Prognosis of persons with type 1 diabetes on intensified insulin therapy in relation to nephropathy
Authors: Mühlhauser I. , Sawicki P. T. , Blank M. , Overmann H. , Bender R. , Berger M.
Published: March 2003

Abstract. Mühlhauser I, Sawicki PT, Blank M, Overmann H, Bender R, Berger M (University of Düsseldorf, Düsseldorf; University of Hamburg, Hamburg; and University of Bielefeld, Bielefeld, Germany). Prognosis of persons with type 1 diabetes on intensified insulin therapy in relation to nephropathy. J Intern Med 2000; 248: 333–341.

Objective. To study the prognosis of persons with type 1 diabetes in relation to the degree of nephropathy at initiation of intensified insulin therapy.

Design. Ten years follow‐up of a cohort of 3674 patients who had participated in a 5‐day group treatment and teaching programme for intensification of insulin therapy between September 1978 and December 1994.

Setting. Ten diabetes centres in Germany.

Subjects. A total of 3674 patients (insulin treatment before age 31), age at baseline 27 ± 10 years, with a diabetes duration of 11 ± 9 years. Patients were divided into three groups according to baseline renal parameters (group I, normal proteinuria, n = 1829; group II, microproteinuria, n = 1257; group III, at least macroproteinuria, n = 367).

Main outcome measures. End‐stage diabetic complications (blindness, amputations, renal replacement therapy), standardized mortality ratios (SMR) and causes of death.

Results. Outcome measures were documented for 97% of patients; 251 (7%) had died. During follow‐up, 1% of patients in group I, 4% in group II, and 47% in group III had at least one end‐stage diabetic complication. SMR for men: nephropathy group I, 2.2 (95% CI = 1.5–3); group II, 3.2 (2.3–4.3); group III, 11.5 (8.8–14.7). SMR for women: group I, 2.5 (1.5–3.8); group II, 3.5 (2.2–5.3), group III, 27 (19.8–35.9). Causes of death for men and women combined: group I (total 58 deaths) – cardiovascular, 21 (36%); hypoglycaemia, 1; ketoacidosis, 3; violent deaths, 17 (29%); others, 16; group II (66 deaths) – cardiovascular, 25 (38%); hypoglycaemia, 2; ketoacidosis, 2; violent deaths, 14 (21%); others, 23; group III (114 deaths) – cardiovascular, 68 (60%); hypoglycaemia, 2; ketoacidosis, 5; infections, 15 (13%); violent deaths, 5 (4%); others, 19.

Conclusions. Patients with microproteinuria have only a slightly worse prognosis than patients with normal proteinuria during the first 10 years after initiation of intensified insulin therapy. Excess mortality amongst patients who started intensified insulin therapy is mainly due to those with manifest clinical nephropathy.
Consulting the source code: prospects for gene‐based medical diagnostics
Authors: Landegren U.
Published: March 2003

Abstract. Landegren U (Rudbeck Laboratory, Uppsala, Sweden) Gene‐based diagnostics (Internal Medicine in the 21st Century). J Intern Med 2000; 248: 271–276.

Gene‐based diagnostics has been slow to enter medical routine practice in a grand way, but it is now spurred on by three important developments: the total genetic informational content of humans and most of our pathogens is rapidly becoming available; a very large number of genetic factors of diagnostic value in disease are being identified; and such factors include the identity of genes frequently targeted by mutations in specific diseases, common DNA sequence variants associated with disease or responses to therapy, and copy number alterations at the level of DNA or RNA that are characteristic of specific diseases. Finally, improved methodology for genetic analysis now brings all of these genetic factors within reach in clinical practice.

The increasing opportunities for genetic diagnostics may gradually influence views on health and normality, and on the genetic plasticity of human beings, provoking discussions about some of the central attributes of genetics.
Gene transfer and the treatment of haematological malignancy
Authors: Brenner M.K.
Published: March 2003

Abstract. Brenner MK. Gene transfer and the treatment of haematological malignancy (Minisymposium). J. Intern Med 2001; 249: 345–358.

Gene therapy offers an additional therapeutic modality for treating haematological malignancy. Because gene therapies could be truly specific for the malignancy, they should ultimately prove both safe and effective. We have far to go before this full potential is realized, but gene transfer strategies are already showing therapeutic promise. Gene transfer may be used to correct the genetic defect in the tumour, to render it more susceptible to conventional therapies, or the normal host cells more resistant, to induce or amplify an antitumour immune response, or simply as a means of tracking the tumour or cells used for treatment. This article describes examples of each approach and discusses future prospects for the field.