bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiplasmin correlates to arterial reactivity in a healthy population of 35‐year‐old men and women
Authors: Johansson J. , Jensen‐Urstad K. , Jensen‐Urstad M.
Published: March 2003

Objective. To study whether haemostasis function variables correlate with endothelial function and other vasomotion characteristics of the brachial artery in a randomly selected healthy population of 35‐year‐old men and women.

Design. Endothelial function was measured as flow mediated dilatation (FMD) of the brachial artery during reactive hyperaemia and the nonendothelial dependent dilatation after sublingual nitroglycerin (NTG) was administered. Haemostasis and fibrinolysis function were estimated by analysis of von Willebrand factor, plasminogen activator inhibitor‐1, antiplasmin and fibrinogen.

Setting. A general medicine research centre and a university hospital.

Subjects. Randomly chosen men (n = 53) and women (n = 56).

Results. Univariate correlation analysis showed significant correlations between haemostasis factors, conventional risk factors for cardio‐ vascular disease and indices of vasomotion of the brachial artery. In multivariate analysis, with haemostasis variables and conventional risk factors included, antiplasmin was the strongest explanatory variable for FMD. When antiplasmin was removed from the analysis, ther‐value dropped from 0.46 to 0.35. Antiplasmin also correlated with NTG‐induced dilatation (positively) and brachial diameter at rest (negatively), albeit less consistently.

Conclusions. Antiplasmin correlates significantly and independently to FMD, reflecting endothelial function, and also to brachial artery diameter at rest and nitroglycerin‐induced dilatation. In multivariate analysis these correlations of antiplasmin to arterial characteristics were stronger than for ‘conventional’ risk factors, such as smoking, blood pressure and serum cholesterol.
Trends in the treatment of patients with myocardial infarction and coronary revascularization procedures in Finland during 1986–92: the FINMONICA Myocardial Infarction Register Study
Authors: Miettinen H. , Salomaa V. , Ketonen M. , Niemelä M. , Immonen‐Räihä P. , Mähönen M.
Published: March 2003

Abstract. Miettinen H, Salomaa V, Ketonen M, Niemelä M, Immonen‐Räihä P, Mähönen M, of the FINMONICA Myocardial Infarction Register Group (Kuopio University Hospital, Kuopio; National Public Health Institute, Helsinki; North Karelia Central Hospital, Joensuu; Loimaa District Hospital, Loimaa; and Turku University Hospital, Turku, Finland). Trends in the treatment of patients with myocardial infarction and coronary revascularization procedures in Finland during 1986–92: the FINMONICA Myocardial Infarction Register Study. J Intern Med 1999; 245: 11–20.

Objectives. To investigate changes in the medical treatment of patients with myocardial infarction and the trends in revascularization procedures in Finland.

Design. A population‐based myocardial infarction (MI) register study.

Setting. Populations, aged 25–64 years, of the three geographical areas of Finland, provinces of North Karelia and Kuopio in eastern Finland and the Turku‐Loimaa area in south‐western Finland.

Main outcome measures. Medical treatment administered prior to the coronary event, during the hospitalization and at discharge from hospital to all patients hospitalized due to suspected myocardial infarction and all CAD deaths occurring during three separate 4‐month periods in 1986, 1989 and 1992. Data on coronary bypass surgery and percutaneous coronary angioplasty in the study areas for 1986–92.

Results. The most marked change in the medical treatment of hospitalized myocardial infarction patients was the significant increase in the use of thrombolytic treatment (5% of patients in 1986 and 24% in 1992, P < 0.001 for trend). The use of antiplatelet agents increased from 1986 to 1992 prior to the coronary event, during the hospitalization and at discharge. The use of beta‐blockers and intravenous nitrates increased and the use of calcium‐channel blockers declined significantly in hospitalized patients during the study period. Hospitalized male myocardial infarction patients were treated more often with beta‐blockers, nitrates, antiplatelet agents and thrombolytic agents than female patients, suggesting less intensive medical treatment in women.

Conclusion. The results of the large clinical trials regarding the medical treatment of myocardial infarction patients were adopted in the clinical practice rapidly and the treatment of myocardial infarction patients and the number of revascularization procedures changed markedly from 1986 to 1992 in Finland. These changes may in part explain the favourable changes in mortality from CAD in Finland.
Oral anticoagulant treatment in patients with mechanical heart valves: how to reduce the risk of thromboembolic and bleeding complications
Authors: Cannegieter S. C. , Torn M. , Rosendaal F. R.
Published: March 2003

Patients with mechanical heart valves have a high risk of thrombus formation on the valve and subsequent systemic embolism. These patients therefore need to receive life‐long oral anticoagulation (OAC). Despite this treatment, the overall incidence rate of major thromboembolic complications is still about 1–2 per 100 patient‐years. Additionally, these patients have an increased risk of bleeding complications, ranging between 1 and 7 per 100 patient‐years.

To reduce both types of often very serious complications, the optimal intensity of anticoagulation needs to be established. We found a fairly wide optimal range between 2.5 and 4.9 INR (international normalized ratio) at which the incidence of both untoward events was minimal. As a target intensity, we recommend opting for the middle of this range (INR 3.0–4.0), thereby providing a safe margin at both ends.

In order to further reduce thromboembolic and bleeding complications, two approaches can be considered: first of all, the management of OAC treatment needs to be optimized in order to achieve a stable therapeutic effect in as many patients as possible. Secondly, patient characteristics need to be identified that increase the thromboembolic or bleeding risk. Subsequently, the optimal intensity may need to be adjusted accordingly, at an individual level. Possible risk factors for an increased thromboembolic risk are position and type of the prosthesis. Age may increase both the risk of thromboembolism and the risk of haemorrhage.
Cutaneous necrosis as a terminal paraneoplastic thromboembolic event in a patient with non‐Hodgkin’s lymphoma
Authors: Luboshitz J. , Bairey O. , Blickstein D. , Vaknin H. , Okon E. , Lahav J. , Prokocimer M.
Published: March 2003

Abstract. Luboshitz J, Bairey O, Blickstein D, Vaknin H, Okon E, Lahav J, Prokocimer M (Rabin Medical Center, Belinson Campus, Petah‐Tikva and Sackler Faculty of Medicine, Tel Aviv University, Israel). Cutaneous necrosis as a terminal paraneoplastic thromboembolic event in a patient with non‐Hodgkin’s lymphoma (Case Report). J Intern Med 1999; 245: 301–5.

Thrombotic complications in non‐Hodgkin’s lymphoma often originate in the large veins. We describe a patient with refractory advanced high‐grade lymphoma who presented with the rare complication of extensive cutaneous necrosis due to thrombosis of dermal vessels; there was also a recent new peak of monoclonal IgM‐κ protein. Direct immunofluorescence demonstrated immune deposits with complement in the dermal vessel wall. Based on these observations and on published data, we suggest that these complexes were the trigger for the thrombotic events and that the monoclonal IgM acted as xenoreactive antibodies, initiating a cascade of events. The first step of this cascade was activation of the complement and the membrane attack complex, which caused secretion of IL‐1α by endothelial cells, followed by overexpression of tissue factor on the surface of the dermal vessel wall endothelium. Dermal vessel thrombosis was the final event in this cascade.
Genes involved in animal models of obesity and anorexia
Authors: Schalling M. , Johansen J. , Nordfors L. , Lönnqvist F.
Published: March 2003

Abstract. Schalling M, Johansen J, Nordfors L, Lönnqvist F (Karolinska Hospital, Stockholm; and Huddinge Hospital, Karolinska Institute, Huddinge, Sweden). Genes involved in animal models of obesity and anorexia. (Minisymposium: Genes & Obesity). J Intern Med 1999; 245: 613–619.

Pathological deviations in bodyweight is a major increasing health problem in industrialized societies. It is currently unclear what genetic mechanisms are involved in the long‐term control of human bodyweight and to what extent these genes are involved in pathological deviations of bodyweight control such as anorexia and obesity. Major support for the concept of genetic control of bodyweight has recently emerged from different animal models. A number of new genes have been found during recent years that, when mutated, have a negative effect on bodyweight in animals and sometimes also in man. Although available evidence points toward a multifactorial nature of weight disorders in most human subjects, the single genes isolated in animal models may become powerful tools to elucidate the genetics also in man. In addition, these genes may serve to promote the development of targeted small‐drug pharmaceuticals aimed at novel biochemical pathways. Finally, the uncovering of several quantitative trait loci (QTL) influencing body mass, body fat or fat topography in the mouse and rat has now also made it possible to perform studies of polygenically caused obesity in rodents. The role of the Genome Project in developing a complete gene map will greatly facilitate transforming these QTLs to actual molecules involved in the biology of bodyweight.
Bleeding complications in secondary stroke prevention by antiplatelet therapy: a benefit–risk analysis
Authors: Boysen G.
Published: March 2003

Abstract. Boysen G (University of Copenhagen, Copenhagen, Denmark). Bleeding complications in secondary stroke prevention by antiplatelet therapy: a benefit–risk analysis (Review). J Intern Med 1999; 246: 239–245.

This review analyses the benefit–risk ratio of antiplatelet drugs in secondary stroke prevention and is based on the published data from eight large stroke prevention trials. In patients with prior transient ischaemic attack (TIA) or stroke, aspirin prevented one to two vascular events (stroke, AMI, or vascular death) per 100 treatment‐years with an excess risk of fatal and severe bleeds of 0.4–0.6 per 100 treatment‐years. The gastrointestinal bleeding risk was significantly lower with ticlopidine and clopidogrel, which were both somewhat more effective than aspirin in the prevention of vascular events. The combination of dipyridamole and aspirin prevented 2.82 strokes at the expense of an excess risk of 0.61 (95% CI = 0.27–0.95) fatal or severe bleeds per 100 treatment‐years.

In the acute phase of stroke, the aspirin‐associated risk of haemorrhagic complications was much increased compared with that in the stable phase after stroke, with 0.48 (95% CI = 0.13–0.83) fatal or severe bleeds per 100 treated patients for the first 4 weeks after stroke in the Chinese Acute Stroke Trial and 0.41 (95% CI = 0.05–0.77) in the International Stroke Trial. Still, there was a net benefit with the prevention of about one death or non‐fatal ischaemic stroke per 100 treated patients.
Antibodies to platelet‐activating factor are associated with borderline hypertension, early atherosclerosis and the metabolic syndrome
Authors: Wu R. , Lemne C. , De Faire U. , Frostegård J.
Published: March 2003

Abstract. Wu R, Lemne C, de Faire U, Frostegård J (Karolinska Hospital and Karolinska Institute, Stockholm, Sweden). Antibodies to platelet‐activating factor (PAF) are associated with borderline hypertension, early atherosclerosis and the metabolic syndrome. J Intern Med 1999; 246: 389–397.

Objective. Platelet‐activating factor (PAF) is a phospholipid inflammatory mediator which is synthesized by a variety of cells, including monocytes and endothelial cells, and PAF can be retained in activated endothelial cell membranes. Furthermore, PAF‐like lipids are produced in other phospholipid membranes as in oxidized LDL. Atherosclerosis is a chronic inflammation in the artery wall, but little is known about the role of immune reactions in the early stages of development of cardiovascular disease. In the present study we investigated if there are antibodies to PAF (aPAF) that may play a role in borderline hypertension and early atherosclerosis.

Design. Seventy‐three men with borderline hypertension (BHT) and 73 age‐matched normotensive (NT) men (diastolic blood pressure 85–94 and <80 mmHg, respectively) were recruited from a population screening programme. Antibody levels were determined by use of ELISA. Carotid intima‐media (IM)‐thickness and atherosclerosis was determined by B‐mode ultrasonography.

Results. BHT men had 49.3% higher aPAF levels of IgG
class than NT controls (P = 0.0007). Antibodies to the biologically inactive lysoPAF did not differ between BHT and NT group. aPAF levels were associated with IM‐thickness in the left (P = 0.02) and right (P = 0.009) carotid artery. Furthermore, aPAF levels were enhanced in individuals with the metabolic syndrome (n = 44) as compared to those without (n = 102; P = 0.009), and also significantly associated with insulin levels (P = 0.02) and insulin resistance (P = 0.02).

Conclusions. aPAF antibodies may reflect early vascular changes and thus serve as novel markers for disease, and they may also be pathogenic, by eliciting an inflammatory reaction in the vascular wall.
Systemic AL amyloidosis in Gaucher disease. A case report and review of the literature
Authors: Kaloterakis A. , Filiotou A. , Koskinas J. , Raptis I. , Zouboulis C. , Michelakakis H. , Hadziyannis S.
Published: March 2003

Abstract. Kaloterakis A, Filiotou A, Koskinas J, Raptis I, Zouboulis C, Michelakakis H, Hadziyannis S
(Hippokration Hospital, and ‘Agia Sofia’ Children’s Hospital, Athens, Greece). Systemic AL amyloidosis in Gaucher disease. A case report and review of the literature (Case Report). J Intern Med 1999; 246: 587–590.

Chronic Gaucher disease [GD] in association with systemic AL amyloidosis is extremely rare. We describe a 46‐year‐old Greek male with chronic GD confirmed by low glucocerebroside activity in fibroblasts and N370S/L444P mutations at the cerebrosidase gene, who also had systemic AL amyloidosis diagnosed by bone marrow diffuse plasmacytosis, serum monoclonal IgA‐λ, severe total proteinuria with monoclonal IgA‐λ, Bence‐Jones‐λ and amyloid deposits in bone marrow, liver, spleen and kidney biopsy specimens. Treatment with melphalan and prednizolon has dramatically decreased both levels of serum M‐IgA and proteinuria and also improved the clinical symptoms of amyloidosis. He died from restrictive cardiac disease 30 months after the diagnosis of amyloidosis. Previously reported cases of GD in association with AL amyloidosis are reviewed.
N‐terminal atrial natriuretic peptide and left ventricular geometry and function in a population sample of elderly males
Authors: Ärnlöv J. , Lind L. , Stridsberg M. , Andrén B. , Lithell H.
Published: March 2003

Abstract. Ärnlöv J, Lind L, Stridsberg M, Andrén B, Lithell H (University of Uppsala, Sweden). N‐terminal atrial natriuretic peptide and left ventricular geometry and function in a population sample of elderly males. J Intern Med 2000; 247: 699–708.

Objectives. To investigate the relationships between N‐terminal atrial natriuretic peptide (N‐ANP) and left ventricular geometry and function.

Design. A cross‐sectional study of a population‐based cohort.

Setting. Follow‐up of a health survey in Uppsala county, Sweden.

Subjects.   Two hundred and five men aged 70.

Main outcome measures. A Delfia sandwich immunoassay was used to measure the plasma levels of N‐ANP. M‐mode and Doppler echocardiographic examinations were used to measure left ventricular dimensions, mass, geometry and systolic function and to classify the subjects into four groups (normal geometry, concentric remodelling, concentric hypertrophy or eccentric hypertrophy). Left ventricular systolic dysfunction was defined as a left ventricular ejection fraction ≤ 0.40.

Results. Plasma levels of N‐ANP were significantly increased in subjects with left ventricular dysfunction compared to healthy subjects (702 ± 486, n = 14 vs. 277 ± 201 pmol L−1, n = 118, P < 0.0001), but there was a great overlap between the groups. N‐ANP differed significantly between the four different left ventricular geometric groups (P = 0.02) with the highest N‐ANP levels in the subjects with left ventricular eccentric hypertrophy (n = 40). However, N‐ANP levels were no longer significantly associated with left ventricular geometry when taking the ejection fraction into account.

Conclusions. This study showed that N‐ANP levels were significantly elevated in subjects with left ventricular dysfunction, as well as in subjects with left ventricular hypertrophy. However, the increase in N‐ANP seen in the eccentric hypertrophy group was mainly due to a decreased ejection fraction.
Should cardiopulmonary resuscitation be performed on patients with heart failure? The role of the patient in the decision‐making process
Authors: Ågård A. , Hermerén G. , Herlitz J.
Published: March 2003

Abstract. Ågård A, Hermerén G, Herlitz J (Lund University and Sahlgrens University Hospital, Göteborg, Sweden). Should cardiopulmonary resuscitation be performed on patients with heart failure? The role of the patient in the decision‐making process. J Intern Med 2000; 248: 279–286.

Objectives. There is an ongoing debate about patients’ involvement in the decision of whether or not to start cardiopulmonary resuscitation (CPR) in the case of cardiac arrest. The objective here is to analyse on what grounds patients with heart failure, who run a relatively high risk of suffering cardiac arrest, form their attitudes towards CPR and to what extent they want to be involved in making decisions concerning CPR.

Design. This study employs a combined qualitative and quantitative interview concerning patients’ knowledge about CPR, their experiences and preferences regarding involvement in making decisions concerning CPR, and their willingness to undergo CPR.

Setting. The study was performed at the Department of Cardiology, Sahlgrens University Hospital, Gothenburg.

Subjects. The subjects involved were 40 patients with various stages of chronic heart failure.

Results. Many of the interviewees lacked fundamental knowledge of CPR. The majority of the patients opted for CPR no matter how small their chances of survival were. The issue had not earlier engaged their thoughts, even less been discussed with physicians. The patients relied on the physician’s ability to judge if CPR was to be regarded as a potentially beneficial intervention or as an unmotivated one. Nevertheless, the patients welcomed the opportunity to take part in the decision‐making process.

Conclusion. In order to make ethically justified decisions, physicians should consider bringing up the question of CPR with patients suffering from heart failure at the point in time where the progressive disease gives rise to more severe symptoms, corresponding to NYHA classes IIIb‐IV. In earlier stages of the disease, one can assume that the patient will opt for CPR unless he or she demonstrates a negative attitude towards life.
C‐reactive protein, cardiovascular risk factors and the association with myocardial infarction in men
Authors: Doggen C. J. M. , Berckmans R. J. , Sturk A. , Manger Cats V. , Rosendaal F. R.
Published: March 2003

Abstract. Doggen CJM, Berckmans RJ, Sturk A, Manger Cats V, Rosendaal FR (Leiden University Medical Center, the Netherlands). C‐reactive protein, cardiovascular risk factors and the association with myocardial infarction in men. J Intern Med 2000; 248: 406–414.

Objectives. This study had three objectives: first, to investigate the association of C‐reactive protein levels and myocardial infarction amongst men; secondly, to study the associations of C‐reactive protein levels with cardiovascular risk factors; and thirdly, to adjust the risk of myocardial infarction for such factors.

Design and subjects. A case–control study including 560 patients with a first myocardial infarction who had survived at least 6 months, plus 646 control subjects.

Results. Patients had significantly higher levels of C‐reactive protein (mean 2.2 mg L−1) than control subjects (mean 1.7 mg L−1; P < 0.001). Persons in the highest quintile of C‐reactive protein had an unadjusted 1.9‐fold increased risk of myocardial infarction compared with persons in the lowest quintile (odds ratio 1.9, 95% CI: 1.3–2.7). C‐reactive protein was, in addition to smoking, associated with several cardiovascular risk factors: age, obesity, diabetes, blood pressure, triglycerides and inversely associated to HDL cholesterol. Adjustment for these variables, especially for total cholesterol, HDL cholesterol and triglycerides, substantially decreased the risk of myocardial infarction for persons in the highest quintile of C‐reactive protein, compared to those in the lowest quintile, to 1.3 (95% CI: 0.9–1.9).

Conclusions. Our findings confirm previous reports that C‐reactive protein predicts the risk of myocardial infarction. However, this association does not appear to be causal, since the increase in risk can to a large extent be explained by the presence of other cardiovascular risk factors.
REVIEW The use of nonhuman primate models to improve gene transfer into haematopoietic stem cells
Authors: Dunbar C. E.
Published: March 2003

Abstract. Dunbar CE (National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville Pike, Bethesda, MD, USA). The use of nonhuman primate models to improve gene transfer into haemotopoietic stem cells. J Intern Med 2001; 249:329–338.

Primitive haematopoietic progenitor and stem cells (HSC) have been pursued as highly desirable targets for genetic therapy as technology allowing safe and controllable transfer of exogenous genes into eukaryotic cells was developed a decade ago. Retroviral vectors have been used for the majority of preclinical and clinical studies directed at these cells, because these vectors have a number of the necessary properties, including chromosomal integration, helper‐free production systems, and lack of toxicity. Until recently, however, results with these vectors in clinical trials and large animal models indicated efficiency of gene transfer as a major hurdle to be overcome. We have focused on using the rhesus macaque autologous transplantation model to optimize gene transfer to primitive haematopoietic cells, and investigate questions regarding in vivo stem cell behaviour, in a system with proven predictive value for human haematopoiesis. By optimization of transduction conditions using standard vectors, gene transfer efficiency to primitive repopulating cells has reached the clinically relevant range of 5–20% long‐term. Alternative vector systems, have also yielded promising results. We have also found that relatively simple manipulation of cell cycle status prior to reinfusion of marked cells results in significantly improved engraftment of transduced cells: this finding may have an impact particularly in the nonablative setting. The high level marking has permitted insertion site analysis and clonal tracking in vivo. Inverse PCR and/or a ligation‐mediated PCR procedure have demonstrated that a large number of transduced clones (over 50) contribute to multiple lineages in vivo for up to at least 2 years post‐transplantation. Thus far we have little evidence for rapid clonal succession or lineage‐restricted engraftment of transduced cells. These and other advances should result in successful gene therapy for a variety of acquired and congenital disorders affecting HSCs and their progeny lineages.
Childbearing and the risk of parathyroid adenoma – a dominant cause for primary hyperparathyroidism
Authors: Rastad J. , Ekbom A. , Hultin H. , Wuu J. , Lundgren E. , Hsieh C‐C. , Lambe M.
Published: March 2003

Rastad J, Ekbom A, Hultin H, Wuu J, Lundgren E, Hsieh C‐C, Lambe M (University Hospital Uppsala, Astra Zeneca R & D, Mölndal, Karolinska Institutet, Stockholm, Sweden, Harvard School of Public Health, Boston, University of Massachusetts Medical Center, Worcester, MA, USA). Childbearing and the risk of parathyroid adenoma – a dominant cause for primary hyperparathyroidism. J Intern Med 2001; 250: 43–49.

Objectives. To explore possible associations between the reproductive history amongst women and the risk of parathyroid adenoma (PA).

Design. Two nationwide Swedish registries. The Fertility Register included data on more than 3.4 million livebirths between 1943 and 1992 amongst Swedish females born 1925–72. The Cancer Register encompasses more than 1800 women with a diagnosis of PA 1960 until 1992.

Setting. All women resident in Sweden 1960–92.

Subjects. Cases were all 1800 women born 1925–72 reported to the Swedish Cancer Registry with a histopathological diagnosis of PA. Five controls were selected at random for each case by matching for the month and year of birth. Conditional logistic regression was used to estimate relative risks of PA.

Main outcomes. Parathyroid adenoma.

Results. High parity (four or more live births) was associated with an increased risk of PA. Amongst women with a diagnosis of PA before menopause (i.e. the age of 50 years) there was an increased risk of PA with younger age at first childbirth. Nulliparous women were at increased risk for PA before menopause, and at decreased risk after menopause.

Conclusions. There is an association between childbearing and the risk of PA, which has not previously been demonstrated, but the underlying biological mechanisms remain to be determined.
Chlamydia pneumoniae and luminal narrowing after coronary angioplasty
Authors: Mattila K. J. , Juvonen J. T. , Kotamäki M. K. , Saikku P. A.
Published: March 2003

Mattila KJ, Juvonen JT, Kotamäki MK, Saikku PA (Helsinki University Hospital, Helsinki; Kainuu Central Hospital, Kajaani, and National Public Health Institute, Oulu, Finland). Chlamydia pneumoniae and luminal narrowing after coronary angioplasty. J Intern Med 2001; 250: 67–71.

Objectives. Numerous studies have linked Chlamydia pneumoniae with atherosclerotic vessel disease and a trend for an association of the bacteria with restenosis after percutaneous transluminae coronary angioplasty (PTCA) has also been observed. The aim of this study was to assess the role of Chlamydia pneumoniae in the luminal narrowing taking place after PTCA.

Design. A noninterventional 6‐month follow‐up study.

Setting. A university hospital.

Subjects. A total of 122 patients with angiographically proven coronary heart disease (CHD) referred for PTCA.

Interventions. None.

Main outcome measures. The degree of luminal narrowing in the coronary arteries following coronary angioplasty.

Results. The levels of C. pneumoniae antibodies (IgG, IgA and IgM classes) and immune complexes were not associated with luminal narrowing after PTCA in multivariate analyses whilst smoking, plasma endothelin levels and diabetes were. The serologic parameters did not change during the follow up either.

Conclusions. These results do not support a role for C. pneumoniae in luminal narrowing following PTCA.
Are patients on long‐term oxygen therapy followed up properly? Data from the Danish Oxygen Register
Authors: Ringbaek T. J. , Lange P. , Viskum K.
Published: March 2003

Abstract. Ringbaek TJ, Lange P, Viskum K (University Hospital of Copenhagen, Hvidovre Hospital; and Gentofte Hospital; Copenhagen, Denmark). Are patients on long‐term oxygen therapy followed up properly? Data from the Danish Oxygen Register. J Intern Med 2001; 250: 131–136.

Objectives. The aim of the study was to assess the extent and quality of follow‐up of patients on LTOT.

Setting. The Danish Oxygen Register.

Subjects. A total of 890 chronic obstructive pulmonary disease (COPD) patients who were on long‐term oxygen therapy (LTOT) during the period from 1 November 1994 to 31 August 1995.

Main outcome measures. The extent and quality of follow‐up.

Results. Only 38.5% of the patients were followed up in the study period, and only 17.5% had a ‘sufficient follow‐up’ defined as at least one follow‐up visit within 10 months which included measurement of arterial blood gases or pulsoximetry with oxygen supply, verification that the patient used oxygen ≥15 h day–1 and was nonsmoker. Female gender, LTOT initiated 3–12 months ago, LTOT started by a chest physician at pulmonary department and LTOT prescribed ≥15 h day–1 were found to be significant predictors of ‘sufficient follow‐up’ (odds ratio (OR): 1.7, 2.0, 3.7 and 1.9, respectively).

Conclusions. The extent and the quality of follow‐up of patients on LTOT were poor, especially if a nonpulmonary physician initiated LTOT. We recommend that more attention should be paid on proper monitoring of LTOT, and that only chest physicians should be able to prescribe and re‐evaluate LTOT.
Antineutrophil cytoplasmatic antibodies in patients with premature atherosclerosis: prevalence and association with risk factors
Authors: VAN HAELST P. L. , ASSELBERGS F. W. , VAN DOORMAAL J. J. , VEEGER N. J. G. M. , MAY J. F. , HOLVOET P. , GANS R. O. B. , TERVAERT J. W. COHEN
Published: March 2003

Abstract. van Haelst PL, Asselbergs FW, van Doormaal JJ, Veeger NJGM, May JF, Holvoet P, Gans ROB, Cohen Tervaert JW (University Hospital Groningen, Groningen, The Netherlands; University of Leuven, Leuven, Belgium). Antineutrophil cytoplasmatic antibodies in patients with premature atherosclerosis: prevalence and association with risk factors. J. Intern Med 2002; 251: 29–34.

Objectives. Autoimmunity is suggested to play a role in premature atherosclerosis. Antineutrophil cytoplasmatic antibodies (ANCA) are a group of autoantibodies found in several inflammatory disorders in which they supposedly amplify the inflammatory process. In this study the hypothesis is tested that ANCA play a role in premature atherosclerosis.

Design. Cross‐sectional study followed by nested case–control study. In a total of 286 consecutive patients with premature atherosclerosis (age < 55 years) ANCA were tested. Within the same cohort, a nested case–control study in 16 ANCA‐positive patients and 32 ANCA‐negative controls matched for sex, and site of atherosclerosis, was executed.

Setting. University hospital outpatient clinic for lipids and premature atherosclerosis.

Subjects. A total of 286 consecutive patients with premature atherosclerosis (age < 55 years).

Results. Prevalence of ANCA was 5.6% (16 of 286). All cases had perinuclear ANCA (pANCA); no cytoplasmatic ANCA was found. Mean age was 42 ± 7 in the ANCA‐positive vs. 42 ± 9 years in the ANCA‐negative group (P=ns). More female parents were ANCA‐positive (8M/8F vs. 200M/70F, P=0.03). Patients with ANCA had more often peripheral vascular disease (37.5 vs. 15.2%, P=0.03). In the case–control study levels of Lp(a) were higher (43.8 vs. 15.6% >300 mg L−1, P=0.05), whereas levels of HDL‐c were lower in ANCA‐positive patients (0.84 ± 0.26 vs. 1.06 ± 0.27 mmol L−1, P=0.01). Markers of inflammation, C‐reactive protein (CRP) and serum amyloid A (SAA), did not differ, nor did antibodies against oxidized‐LDL and malondialdehyde (MDA)‐LDL, markers for the extent of atherosclerosis.

Conclusions. Our results suggest that ANCA do not appear to play a major role in premature atherosclerosis as there was no increased prevalence of the autoantibody. Moreover, no differences in the incidence of classical cardiovascular risk factors nor in serum levels of markers of inflammation were found between the ANCA‐positive group as compared with the ANCA‐negative group.
Exploring sex differences in case fatality in acute myocardial infarction or coronary death events in the northern Sweden MONICA Project
Authors: Lundberg V. , Wikström B. , Boström S. , Asplund K.
Published: March 2003

Abstract. Lundberg V, Wikström B, Boström S, Asplund K (Kalix Hospital and Umeå University Hospital, Sweden). Exploring sex differences in case fatality in acute myocardial infarction or coronary death events in the northern Sweden MONICA Project. J Intern Med 2002; 251: 235–244.

Objectives. To investigate sex differences in reaching diagnosis, medical management and case fatality (CF) in acute myocardial infarction (AMI) in the population aged 35–64 years in northern Sweden.

Methods. Within the framework of the World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Diseases (MONICA) Project, definite AMI was monitored in people aged 35–64 years from 1989 through 1995 (target population 510 000 in 1991).

Setting. In a population based coronary register, all coronary events were recorded in nine hospitals in 1989–95.

Results. The number of events included in the definite coronary myocardial infarction register was 2483 men and 669 women. On admission, a higher proportion of men with definite AMI had chest pain or ECG changes typical for AMI (P < 0.0001). Disagreement between clinical diagnosis and classification by MONICA criteria occurred more often in women (P=0.008). A significantly higher proportion of men was admitted in the coronary care unit and they were significantly more often treated with thrombolytics, nitroglycerine, β‐blockers, or antiplatelet agents. Women received significantly more diuretics, inotropics or calcium antagonists. Diabetes, conferring a worse prognosis, was more common in women (20 vs. 15%; P=0.003). Prehospital CF was significantly higher in men (24.1 vs. 18.3%; P=0.005), but in patients treated in hospital, the CF was significantly lower in men (12.7 vs. 21.2%; P < 0.001). Total CF was equal in men and women.

Conclusions. Several factors contributing to the excess in‐hospital CF in women were identified, including greater problems in diagnosis of AMI in women which may be one of the reasons for less intensive treatment in women. Differences in co‐morbidity, most notably diabetes and medical treatment between men and women with acute AMI may also have played a part.
On the diagnosis of polycythaemia vera as assessed in the health and medical care in the Västra Götaland region, Sweden
Authors: JOHANSSON P. , ANDRÉASSON B. , SAFAI‐KUTTI S. , RHEDIN C. , VILÉN L. , VÄÄRT J. , KUTTI J.
Published: March 2003

Abstract. Johansson P, Andréasson B, Safai‐Kutti S, Rhedin C, Vilén L, Väärt J, Kutti J (Sahlgrenska University Hospital, Göteborg; Uddevalla Hospital, Uddevalla; Borås Hospital, Borås; and Skövde Hospital, Skövde; Sweden). On the diagnosis of polycythaemia vera as assessed in the health and medical care in the Västra Götaland region, Sweden. J Intern Med 2002; 251: 348–354.

Objective. The aim was to assess how the diagnosis of polycythaemia vera (PV) was established and to study to which extent the classic Polycythemia Vera Study Group (PVSG) criteria and the revised criteria for the diagnosis of PV as proposed by Pearson and Messinezy in 1996 (PM criteria) were fulfilled when the diagnosis of PV was made.

Design and setting. A questionnaire was sent to physicians in charge of haematological patients at the departments of medicine in 12 hospitals in the Health and Medical Care in the Västra Götaland Region (VGR), Sweden, with a population of 1.5 million inhabitants; they were asked to provide reports as regards all patients with an unequivocal diagnosis of PV during a 5‐year period from January 1994 to December 1998.

Subjects. Full reports were obtained from six hospitals, which serve about 1.1 million inhabitants. The results from a total of 129 PV patients, 62 from two university hospitals (UHs) and 67 from four county hospitals (CHs), were the subject of the present analysis.

Results. It was shown that measurement of the red cell mass (RCM) had been carried out in 61 of 62 (98%) patients in UHs compared with 24 of 67 (36%) patients at CHs (P < 0.01). By using ultrasound imaging and/or scintigraphy the spleen size had been determined in 55 of 62 (89%) patients at UHs and in 24 of 67 (36%) patients at CHs (P < 0.01). At the UHs, arterial oxygen saturation had been measured in 32 of 62 (52%) patients; the corresponding figure for the CH patients was 22 of 67 (33%). Plasma or serum erythropoietin (EPO) concentrations had been measured in 44 of 62 (71%) of PV patients at UHs and in 31 of 67 (46%) of patients at CHs; in all these cases the EPO concentrations were subnormal or not measurable.

Conclusions. At the UHs only 37% of the PV patients fulfilled the PVSG criteria for the diagnosis of PV whereas the corresponding figure for CHs was 4% (P < 0.01). The adherence to PM criteria was, however, 71% at UHs compared with 16% at CHs (P < 0.01).
Factors predicting a hospital stay of over 3 days in patients with acute exacerbation of chronic obstructive pulmonary disease
Authors: De La Iglesia F. , Valiño P. , Pita S. , Ramos V. , Pellicer C. , Nicolás R. , Diz‐Lois F.
Published: March 2003

Abstract. de la Iglesia F, Valiño P, Pita S, Ramos V, Pellicer C, Nicolás R, Diz‐Lois F (Juan Canalejo Hospital, A Coruña, Spain). Factors predicting a hospital stay of over 3 days in patients with acute exacerbation of chronic obstructive pulmonary disease. J Intern Med 2002; 251: 500–507.

Objective. To investigate the factors predicting a hospital stay of over 3 days in patients who required hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD).

Design and setting. A cross‐sectional tudy was done at a tertiary hospital serving an area of 500 000 inhabitants.

Subjects. A total of 273 patients (α=0.05; accuracy=5.94%) who had been admitted consecutively to the Short Stay Medical Unit at the Juan Canalejo Hospital in A Coruña, from February 1998 to March 1999, with a diagnosis focusing on exacerbation of COPD.

Methods. Demographic variables, past medical history, symptoms, arterial blood gases, functional tests, treatment and the cause of exacerbation were studied in each patient. The hospital stay was dichotomized into ≤3 vs. >3 days. The prognostic factors of a hospital stay were determined by log regression.

Results. The mean stay was 4.6 ± 5.1 days (range: 1–64). After monitoring the associated covariables, the following were found to have an independent effect on the prediction of a hospital stay of over 3 days: weekend admissions (OR=4.17; 95% CI: 2.42–7.18), the presence of cor pulmonale (OR=2.19; 95% CI: 1.27–3.78), and the respiratory rate on admission (OR=1.09; 95% CI: 1.03–1.14). Arterial blood gases and functional tests showed no independent effect.

Conclusions. The factors having an independent prognostic value in determining the length of hospital stays in patients with COPD are weekend admission, cor pulmonale and respiratory rate. Additional studies are required to validate these findings.
Cutaneous gene transfer for skin and systemic diseases
Authors: KHAVARI P. A. , ROLLMAN O. , VAHLQUIST A.
Published: March 2003

This article is partially based on the findings presented at a symposium on Cutaneous Gene Therapy, held in Uppsala, September 2001, and abstracted in Acta Derm Venereol 81: 227–239.

Abstract. Khavari PA, Rollman O, Vahlquist A (Stanford University School of Medicine, Stanford, CA, USA; and Department of Medical Sciences, Dermatology, Uppsala University, Uppsala, Sweden). Cutaneous gene transfer for skin and systemic diseases (Review). J Intern Med 2002; 252: 1–10.

Recent progress in molecular genetics has illuminated the basis for a wide variety of inherited and acquired diseases. Gene therapy offers an attractive therapeutic approach capitalizing upon these new mechanistic insights. The skin is a uniquely attractive tissue site for development of new genetic therapeutic approaches both for its accessibility as well as for the large number of diseases that are amenable in principle to cutaneous gene transfer. Amongst these opportunities are primary monogenic skin diseases, chronic wounds and systemic disorders characterized by low or absent levels of circulating polypeptides. For cutaneous gene therapy to be effective, however, significant progress is required in a number of domains. Recent advances in vector design, administration, immune modulation, and regulation of gene expression have brought the field much nearer to clinical utility.
Development of hypertension over 6 years in a birth cohort of young middle‐aged men: the Cardiovascular Risk Factor Study in southern Sweden (CRISS)
Authors: HENRIKSSON K. M. , LINDBLAD U. , GULLBERG B. , ÅGREN B. , NILSSON‐EHLE P. , RÅSTAM L.
Published: March 2003

Abstract. Henriksson KM, Lindblad U, Gullberg B, Ågren B, Nilsson‐Ehle P, Råstam L (Lund University, Skaraborg Institute and Helsingborg County Hospital, Sweden). Development of hypertension over 6 years in a birth cohort of young middle‐aged men: the Cardiovascular Risk Factor Study in southern Sweden (CRISS). J Intern Med 2002; 252: 21–26.

Objectives. To explore the development of hypertension (HT) in a cohort of young middle‐aged men.

Design. Prospective birth‐cohort study of men surveyed over 6 years.

Setting. Helsingborg County Hospital, Sweden, 1990–97.

Subjects. A total of 628 men born in 1953–54, all surveyed at 37, 40 and 43 years of age.

Main outcome measures. Systolic blood pressure (SBP), diastolic blood pressure (DBP), S‐cholesterol, body mass index (BMI), alcohol consumption, ethnicity. HT was defined as SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg, or ongoing treatment. Using SBP < 130 mmHg and DBP < 85 mmHg as reference, the odds of conversion to HT in men with high normal blood pressure (BP) (SBP 130–139 mmHg and DBP 85–89 mmHg) was investigated.

Results. At age 37, 243 men (39%) had reference BP, 167 (26%) had high normal BP and 218 (35%) were hypertensive. Corresponding numbers at age 40 were 265 (42%), 166 (27%) and 197 (31%); and at age 43, 180 (29%), 142 (22%) and 306 (49%), respectively. High normal BP at baseline was associated with the development of HT both at age 40 (odds ratio (OR)=2.45 confidence interval (CI): 1.42–4.22) and at age 43 (OR=2.46, CI: 1.59–3.80), independent of other cardiovascular disease risk factors and ethnicity. The progression to HT was predicted also by S‐cholesterol, alcohol consumption, BMI and weight gain.

Conclusions. Over a short‐term period, a substantial proportion of young middle‐aged men with high normal BP develop HT with overweight and alcohol consumption as important determinants. These findings have implications for the prevention, screening and medical care of HT in this target population.
Kikuchi–Fujimoto's disease: report of familial occurrence in two human leucocyte antigen‐identical non‐twin sisters
Authors: AMIR A. R. A. , AMR S. S. , SHEIKH S. S.
Published: March 2003

Abstract. Amir ARA, Amr SS, Sheikh SS (Dhahran Health Center, Saudi Arabia). Kikuchi–Fujimoto's disease: report of familial occurrence in two human leucocyte antigen‐identical non‐twin sisters (Case Report). J Intern Med 2002; 252: 79–83.

Kikuchi–Fujimoto's disease (KFD) is a self‐limiting condition usually presenting as cervical lymphadenopathy, with fever and leukopenia, in young adult females. No specific aetiology has been identified yet, although some authors believe that KFD is a `forme fruste' of systemic lupus erythematosus. Certain human leucocyte antigen (HLA) types have also been associated with KFD.

We herein report KFD in two non‐twin sisters with HLA‐identical phenotype, who presented 10 years apart. Neither patient had evidence of recent infection or connective tissue disease. The familial occurrence emphasizes the possibility of genetic predisposition and calls for a more extensive search for a specific cause of KFD.
Residual insulin secretion is not coupled to a maintained glucagon response to hypoglycaemia in long‐term type 1 diabetes
Authors: Sjöberg S. , Ahrén B. , Bolinder J.
Published: March 2003

Objectives.  To evaluate the influence of residual β‐cell function on glucagon secretion and glucose counter‐regulation following hypoglycaemia in type 1 diabetes.

Design and subjects.  The hormonal counter‐regulatory responses to standardized insulin‐induced hypoglycaemia were investigated, 18 patients with type 1 diabetes of long duration and 12 healthy subjects were investigated. Nine of the diabetic patients (diabetes duration 17 ± 1 years) had residual insulin secretion, as reflected by persistent urinary C‐peptide excretion. The other nine diabetic patients (diabetes duration 21 ± 1 years) were C‐peptide negative.

Results.  Similar hypoglycaemic nadirs were found in all groups (2.1–2.3 mmol L−1), whereas the recovery of plasma glucose levels was delayed similarly in the diabetic groups. In the control subjects, plasma glucagon increased (∼50%). No significant glucagon response was registered in either of the two diabetic groups. The maximum plasma adrenaline and pancreatic polypeptides (PP) responses to hypoglycaemia were comparable in the two diabetic patient groups; the peak values being lower (P < 0.05) than in the controls. Plasma noradrenaline, growth hormone and cortisol responses to hypoglycaemia were similar in all three groups.

Conclusion.  Residual β‐cell function in patients with long‐term type 1 diabetes is not accompanied by preservation of the glucagon response to hypoglycaemia. As the two markers of autonomic function (adrenaline and PP) were similarly reduced in the two diabetic groups, the findings instead favour the concept that the defective glucagon secretory response to hypoglycaemia is because of autonomic nervous dysfunction.
Longitudinal bone loss in postmenopausal women with primary biliary cirrhosis and well‐preserved liver function
Authors: Ormarsdóttir S. , Ljunggren Ö. , Mallmin H. , Olsson R. , Prytz H. , Lööf L.
Published: March 2003

Abstract.  Ormarsdóttir S, Ljunggren Ö, Mallmin H, Olsson R, Prytz H, Lööf L (University Hospital, Uppsala; Sahlgrenska University Hospital, Gothenburg; University Hospital, Lund; and Central Hospital, Västerås, Sweden). Longitudinal bone loss in postmenopausal women with primary biliary cirrhosis and well‐preserved liver function. J Intern Med 2002; 252: 537–541.

Objectives/design.  Increased rate of bone loss has been reported in women with primary biliary cirrhosis (PBC) and varying degree of liver dysfunction. Whether bone loss is increased in patients without liver dysfunction is unclear. The aim of this study was to estimate retrospectively the rate of bone loss in postmenopausal women with PBC and well‐preserved liver function.

Subjects/interventions.  Forty‐three women with PBC, and classified as Child‐Pugh class A, were included. Bone mineral density (BMD) was measured by dual energy X‐ray absorptiometry at the lumbar spine and the femoral neck.

Results.  Median time between measurements of BMD was 26 months (range, 12–48 months). Twenty women were not receiving any bone protective treatment, i.e. hormone replacement therapy (HRT), bisphosphonates or vitamin D/calcium supplementation, whilst 23 women received such treatment. Mean annual bone loss in the former group was 0.38 ± 2.56% and 0.42 ± 2.29% at the lumbar spine and the femoral neck, respectively. Women receiving treatment, however, increased their BMD by 1.92 ± 3.76% and 0.15 ± 2.75% at the lumbar spine and the femoral neck, respectively. At the lumbar spine the difference with regard to changes in BMD between untreated and treated women was statistically significant (P = 0.02). Women who received HRT (n = 11) increased their BMD at the lumbar spine by 2.95 ± 3.91%, P = 0.03 when compared with untreated women.

Conclusion.  Bone loss in postmenopausal women with PBC and well‐preserved liver function is not increased above normal. Treatment with bone protective treatment, mainly HRT, improves BMD at the lumbar spine.