bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved fibrinolysis by intense lifestyle intervention. A randomized trial in subjects with impaired glucose tolerance
Authors: Lindahl B. , Nilsson T. K. , Jansson J.‐H. , Asplund K. , Hallmans G.
Published: March 2003

Objective. To assess the effects of lifestyle intervention on cardiovascular risk factors in general and especially on fibrinolysis.

Design. Randomized clinical study.

Subjects. A total of 186 subjects with impaired glucose tolerance and obesity.

Interventions. The intervention programme included a low‐fat, high‐fibre diet and regular physical exercise. Half of the participants (n = 93) took part in a one‐month learning and training session using different behavioural modification techniques and conducted in a full‐board wellness centre (intense intervention group). The other half (n = 93) was randomized a one‐hour counselling session with a specially trained nurse (usual care group). Follow‐up was carried out after 12 months.

Main outcome measures. Body weight, oxygen consumption, plasminogen activator inhibitor type 1 (PAI‐1) activity, tissue plasminogen activator (tPA) antigen, fibrinogen and fasting plasma insulin measured at the start of the programme and at follow‐up after 1 year.

Results. The intense intervention group had a mean weight decline by 1 year of 5.4 kg compared to 0.5 kg in the usual care group. Oxygen consumption in the intense group increased 10% vs. a 1% decline in the usual care group. In the intense group, PAI‐1 activity decreased 31% (– 10.1 U mL–1), which was significantly more than in the usual care group (12%; – 3.0 U mL–1). The corresponding reductions in tPA antigen were 14% (– 1.65 μg L–1) and 6% (– 0.69 μg L–1).

Conclusions. The present randomized study shows that an intense lifestyle programme has sustained beneficial effects on fibrinolysis.
Trends in lipid levels and hypercholesterolemia in hypertensive and normotensive Finnish adults from 1982 to 1997
Authors: Kastarinen M. , Tuomilehto J. , Vartiainen E. , Jousilahti P. , Sundvall J. , Puska P. , Nissinen A.
Published: March 2003

Abstract. Kastarinen M, Tuomilehto J, Vartiainen E, Jousilahti P, Sundvall J, Puska P, Nissinen A (University of Kuopio, Kuopio; National Public Health Institute, Helsinki; Kuopio University Hospital, Kuopio, Finland). Trends in lipid levels and hypercholesterolemia in hypertensive and normotensive Finnish adults from 1982 to 1997. J Intern Med 2000; 247: 53–62.

Objectives. To assess the trends in lipid levels and awareness of hypercholesterolemia in hypertensive and normotensive population in Finland from 1982 to 97.

Design. Four independent cross‐sectional population surveys conducted in 1982, 1987, 1992 and 1997.

Setting. The provinces of North Karelia and Kuopio in eastern Finland and the region of Turku‐Loimaa in south‐western Finland.

Subjects. Men and women aged 25–64 years, selected randomly from the national population register. The subjects were classified to four groups according to their blood pressure level and treatment status: normotensive, unaware hypertensive, aware but not treated hypertensive and treated hypertensive. The total number of participants was 24 083.

Main outcome measures. We assessed the mean serum total cholesterol and HDL cholesterol concentrations, the prevalence of hypercholesterolemia (total cholesterol ≥6.5 mmol L–1 or the use of lipid‐lowering drugs), the prevalence of a high ratio of total cholesterol to HDL cholesterol (ratio ≥5) and the awareness of hypercholesterolemia amongst the four study groups.

Results. Mean total cholesterol, the prevalence of hypercholesterolemia and the prevalence of a high ratio of total to HDL cholesterol decreased, whereas the awareness of hypercholesterolemia increased significantly in all study groups. The decline in mean total cholesterol was largest in treated hypertensive subjects of both sexes (13% in men, 14% in women). Mean HDL cholesterol increased significantly in all study groups except in the unaware hypertensive men, but it remained significantly lower in treated hypertensive patients in both sexes compared with the other groups (P < 0.001).

Conclusions. The lipid profile of both the hypertensive and normotensive population has significantly improved in both the hypertensive and normotensive population in Finland from 1982–97. The introduction of newer antihypertensive drugs has not had any effect on the HDL cholesterol level amongst treated hypertensive patients at the population level.
Non‐linear effects of blood pressure and glycosylated haemoglobin on progression of diabetic nephropathy
Authors: Sawicki P. T. , Bender R. , Berger M. , Mühlhauser I.
Published: March 2003

Abstract. Sawicki PT, Bender R, Berger M, Mühlhauser I (WHO‐Collaborating Centre for Diabetes, Heinrich‐Heine‐University of Düsseldorf, Germany). Non‐linear effects of blood pressure and glycosylated haemoglobin on progression of diabetic nephropathy. J Intern Med 2000; 247: 131–138.

Objective. To describe the long‐term simultaneous impacts of blood pressure and glycosylated haemoglobin values on the risk of progression of diabetic nephropathy.

Design. Prospective, multicentre, 6‐year follow‐up study.

Setting. One reference centre (university department of internal medicine) and nine general hospitals.

Subjects. A total of 601 type 1 diabetic patients on intensive insulin therapy with and without diabetic nephropathy.

Main outcome measures. Progression of nephropathy was defined as change for the worse within five stages of nephropathy by at least one of these stages during the study period. By the use of logistic regression, the relationship between metabolic and blood pressure control and the risk of nephropathy progression was quantified.

Results. The main determinants of nephropathy progression were glycosylated haemoglobin and blood pressure, which were both non‐linearly associated with the risk of progression. No significant threshold levels for any of the predictors of progression were identified.

Conclusions. The results of this study underline the importance of optimizing metabolic and blood pressure control to arrest the progression of diabetic nephropathy without the evidence for a clinically relevant threshold effect.
Marked improvement in survival after acute myocardial infarction in middle‐aged men but not in women. The Northern Sweden MONICA study 1985–94
Authors: Peltonen M. , Lundberg V. , Huhtasaari F. , Asplund K.
Published: March 2003

Abstract. Peltonen M, Lundberg V, Huhtasaari F, Asplund K (Umeå University Hospital, Kalix Hospital and Luleå‐Boden Hospital, Sweden). Marked improvement in survival after acute myocardial infarction in middle‐aged men but not in women. The Northern Sweden MONICA study 1985–94. J Intern Med 2000; 247: 579–587.

Objectives. The aim of this study was to analyse time trends in survival after acute myocardial infarction with special emphasis on sex differences.

Design. Within the framework of the population‐based WHO MONICA Project, all acute myocardial infarction events were recorded in the age group 25–64 years in northern Sweden during the period 1985–94. All first‐ever myocardial infarction patients were followed for information on vital status.

Subjects. A total of 3397 men and 860 women with acute myocardial infarction, during the period between 1985 and 1994.

Main outcome measures. Case fatality rates after first‐ever acute myocardial infarction.

Results. When compared with the 1985–86 cohort, the age‐adjusted odds ratio for death within 1 year after acute myocardial infarction was 0.59 (95% CI 0.46–0.76) in the 1993–94 male cohort but 0.99 (95% CI 0.61–1.60) in the female 1993–94 cohort. Corresponding age‐adjusted proportions of death within 1 year were 33.3% and 22.9% in men and 27.5% and 27.3% in women in 1985–86 and 1993–94, respectively. The odds ratio for 3‐year case fatality amongst those who survived the first 28 days was 0.34 (95% CI 0.21–0.55) in 1991–92 compared with 1985–86 in men and 0.91 (0.43–1.94) in women.

Conclusion. Both short‐ and long‐term survival after AMI have improved markedly in men over the last decade. There is a disturbing sex difference in that, during the same period, survival in women with AMI has not improved at all. This sex difference was not explained by differences in conventional prognostic factors.
Bezafibrate and simvastatin combination therapy for diabetic dyslipidaemia: efficacy and safety
Authors: Gavish D. , Leibovitz E. , Shapira I. , Rubinstein A.
Published: March 2003

Abstract. Gavish D, Leibovitz E, Shapira I, Rubinstein A (Wolfson Medical Center, Holon, and Tel Aviv Sourasky Medical Center, Tel Aviv, Israel). Bezafibrate and simvastatin combination therapy for diabetic dyslipidaemia: efficacy and safety. J Intern Med 2000; 247: 563–569.

Objective. To determine the efficacy and safety of a statin–fibrate combination in diabetes patients.

Design.   An open 21‐month trial in which each patient first received the single drug for 6 months and then a combination of the two for 1 year.

Setting. Three lipid clinics in university‐based tertiary care hospitals.

Patients. One hundred and forty‐eight patients with type 2 (non‐insulin‐dependent, NIDDM) diabetes mellitus under stable control for 3 months by means of diet and oral hypoglycaemic medication.

Intervention. Patients from one clinic (n = 48) received bezafibrate slow release (400 mg day–1), and patients from the other two clinics (n = 100) received simvastatin 20 mg day–1. Six months later, all patients were switched to a daily combination of 400 mg bezafibrate slow release and 20 mg simvastatin for 1 year.

Results. The combination of statin and fibrate led to a 23% reduction in total cholesterol, 42% reduction in triglycerides, 29% reduction in LDL‐c, 25% increase in HDL‐c, 10% decrease in fibrinogen and 19% reduction of Lp(a) levels, and a decrease in the cholesterol/HDL‐c ratio (from 8.9 to 5.4) in all 148 patients. Cardiovascular (CV) event rate was significantly reduced from 9.5% during the first 6 months of the study to less than 2% during the last year of the study (whilst on combination Rx). Side‐effects with all treatments included only two patients who developed myopathy when on the combined regimen and one on the single statin regimen. However, plasma creatinine phosphokinase (CPK) levels doubled (but remained within the normal range) in most of the patients on combination therapy, compared with only a mild increase in patients receiving a single medication.

Conclusions. The statin and fibrate combination was found to be more efficacious than a single medication for treatment of diabetic dyslipidaemia, as evidenced by improvement in the lipoprotein profile, reductions in Lp(a), fibrinogen and CV event rate, and almost no clinically significant side‐effects.
Reduced thiamine phosphate, but not thiamine diphosphate, in erythrocytes in elderly patients with congestive heart failure treated with furosemide
Authors: Härdig L. , Daae C. , Dellborg M. , Kontny F. , Bøhmer T.
Published: March 2003

Abstract. Härdig L, Daae C, Dellborg M, Kontny F, Bøhmer T (Sahlgrenska University Hospital/Östra, Göteborg, Sweden, and Aker University Hospital, Oslo, Norway). Reduced thiamine phosphate, but not thiamine diphosphate, in erythrocytes in elderly patients with congestive heart failure treated with furosemide. J Intern Med 2000; 247: 597–600.

Objectives. To measure the concentrations of thiamine and thiamine esters by high‐pressure liquid chromatography (HPLC) in elderly patients treated with furosemide for heart failure and in a control group.

Design. A cross‐sectional study of blood thiamine and thiamine ester concentrations.

Subjects. Forty‐one patients admitted to hospital for heart failure and 34 elderly living at home. No vitamin supplementation was allowed.

Results. Compared with the healthy controls, furosemide‐treated patients had significantly reduced whole blood thiamine phosphate (TP; 4.4 ± 2.2 vs. 7.6 ± 2.0 nmol L–1) and thiamine diphosphate (TPP; 76 ± 21.5 vs. 91 ± 19.8 nmol L–1) (mean ± SD). When the thiamine concentrations were related to the haemoglobin concentrations, which were reduced in the heart failure patients, the levels of TP (nmol g–1 Hb) were 0.38 ± 0.26 vs. 0.54 ± 0.17 (P < 0.0001), and of TPP were 6.35 ± 1.76 vs. 6.37 ± 1.29 (P = 0.95). There were no differences in T and TP concentrations in plasma between the two groups.

Conclusions. The elderly patients with heart failure treated with furosemide have not reduced the storage form of thiamine, TPP, but only TP. This change is most likely not an expression of a thiamine deficiency, but rather of an altered metabolism of thiamine, which is not understood at present.
The EWA (Estrogen in Women with Atherosclerosis) Study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins
Authors: Os I. , Hofstad A. E. , Brekke M. , Abdelnoor M. , Nesheim B. I. , Jacobsen A. F. , Birkeland K. , Larsen A. , Midtbø K. , Westheim A.
Published: March 2003

Abstract. Os I, Hofstad AE, Brekke M, Abdelnoor M, Nesheim BI, Jacobsen AF, Birkeland K, Larsen A, Midtbø K, Westheim A (Ullevaal University Hospital and Aker University Hospital, Oslo, Norway). The EWA (Estrogen in Women with Atherosclerosis) Study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins. J Intern Med 2000; 247: 433–441.

Objectives. To evaluate the effects of hormone replacement therapy (HRT) on lipids and lipoproteins in postmenopausal women with coronary artery disease.

Setting. In this single‐centre, controlled and randomized study taking place in a tertiary referral clinic, patients were examined at baseline, and after 3 and 12 months. All analyses were performed examiner‐blind.

Subjects. Postmenopausal women (n = 118) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease.

Interventions. The women were randomized to HRT, i.e. transdermal application of continuous 17‐β oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days, or to a control group.

Main outcomes. Effects on lipids and lipoproteins.

Results. After 3 months of unopposed oestradiol, triglycerides decreased significantly compared to the control group (P = 0.006). Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol (P = 0.01), concomitantly with a decrease in ApoA1 lipoproteins (P = 0.007). No other changes in lipids or lipoproteins were observed. After 12 months of therapy, no significant differences were observed between the two groups in lipid or lipoprotein levels. Concomitant statin treatment did not alter the main findings.

Conclusions. In postmenopausal women with established coronary artery disease in whom the majority is treated with statins, no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase. No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins.
Desmopressin and hexarelin tests in alcohol‐induced pseudo‐Cushing’s syndrome
Authors: Coiro V. , Volpi R. , Capretti L. , Caffarri G. , Chiodera P.
Published: March 2003

Abstract. Coiro V, Volpi R, Capretti L, Caffarri G, Chiodera P (University of Parma, Parma, the Hospital of Codogno, Codogno and the Hospital of Guastalla, Guastalla, Italy). Desmopressin and hexarelin tests in alcohol‐induced pseudo‐cushing’s syndrome. J Intern Med 2000; 247: 667–673.

Background. A challenge in clinical endocrinology is the distinction between Cushing’s disease (Cushing’s syndrome dependent by adrenocorticotrophic hormone (ACTH)‐secreting tumours of pituitary origin) and alcohol‐dependent pseudo‐Cushing’s syndrome. Patients with Cushing’s disease are known to have high ACTH/cortisol responses to desmopressin (DDAVP, a vasopressin analogue) and to hexarelin (HEX, a synthetic GH‐releasing peptide).

Objective. To compare the ACTH/cortisol responses to desmopressin and to hexarelin of subjects with alcohol pseudo‐Cushing’s syndrome with those obtained in patients with Cushing’s disease and in normal controls.

Design. Randomized, single‐blind study.

Setting. University medical centre.

Subjects. Eight alcoholics with pseudo‐Cushing’s syndrome, six patients with Cushing’s disease and nine age‐matched normal controls.

Intervention. Three tests at weekly intervals. The dexamethasone (1 mg) suppression test (DST) was carried out first. The desmopressin (10 μg intravenously at 09:00 h) test and hexarelin (2 μg kg–1 intravenously at 09:00 h) test were carried out in random order.

Measurements. Plasma ACTH and cortisol levels.

Results. The basal plasma levels of ACTH and cortisol were significantly lower in normal subjects than in patients with Cushing’s disease and in alcoholic subjects; these latter groups showed similar basal hormonal values. All normal controls, two patients with Cushing’s disease and two alcoholics showed suppression of plasma cortisol levels (<5 μg dL–1) after dexamethasone administration. Both desmopressin and hexarelin induced striking ACTH/cortisol responses in patients with Cushing’s disease, whereas hexarelin, but not desmopressin, slightly increased ACTH/cortisol secretion in the normal controls. Neither desmopressin nor hexarelin administration induced any significant change in ACTH/cortisol secretion in alcoholics.

Conclusions. These data suggest that either the hexarelin or desmopressin test can be used to differentiate patients with Cushing’s disease from subjects with alcohol‐dependent pseudo‐Cushing’s syndrome.
Independent importance of psychosocial factors for prognosis after myocardial infarction
Authors: Welin C. , Lappas G. , Wilhelmsen L.
Published: March 2003

Abstract. Welin C, Lappas G, Wilhelmsen L (Heart and Lung Institute, Göteborg University, Göteborg, Sweden). Independent importance of psychosocial factors for prognosis after myocardial infarction. J Intern Med 2000; 247: 629–639.

Aims. As a primary aim it was tested whether the 10‐year prognosis after a myocardial infarction is related to psychological stress, lack of social support, anxiety, and/or depressive tendency. A secondary aim was to analyse the prognostic importance of a series of other psychosocial factors as well as interactions.

Methods. Non‐selected patients aged below 65 years with a first infarction (230 men and 45 women) were followed for 10 years with 100% assessment of morbidity and cause‐specific mortality. Baseline somatic and psychosocial variables were collected with the aid of standard, validated questionnaires.

Results. In multivariate analysis, factors increasing risk for coronary mortality included female sex
(hazard ratio, ± 95% confidence interval) 2.47 (1.06, 5.71), signs of left ventricular failure 3.93 (1.87, 8.26), ventricular dysrhythmia 3 months after the infarction 5.45 (2.21, 13.42), high depression scores 3.16 (1.38, 7.25) and lack of social support 2.75 (1.29, 5.89). All‐cause mortality was significantly related to left ventricular failure, ventricular dysrhythmias, and high depression scores with borderline significance for female sex and social support. Prognosis was affected during the entire follow‐up period. It was not significantly associated with age, marital status, education, extra work, mental strain at work or in the marriage, anxiety, dissatisfaction with family life, problems with children, dissatisfaction with the financial situation, life events, anger‐in, irritability, type A behaviour, or health locus of control. Incidence of nonfatal infarction was not associated with any of the baseline variables.

Conclusion. In addition to known somatic predictors of prognosis after a myocardial infarction, prognosis is strongly influenced by depression and lack of social support, but not to a series of other psychosocial factors. It is recommended to use self‐reporting scales to detect prognostically important psychosocial problems.
Risk assessment in patients with acute myocardial infarction treated with thrombolytic therapy
Authors: Jensen‐Urstad M. , Samad B. A. , Jensen‐Urstad K. , Hulting J. , Ruiz H. , Bouvier F. , Höjer J.
Published: March 2003

Abstract. Jensen‐Urstad M, Samad BA, Jensen‐Urstad K, Hulting J, Ruiz H, Bouvier F, Höjer J (Karolinska Hospital, Karolinska Institute, Stockholm; Söder Hospital, Karolinska Institute, Stockholm; Karolinska Hospital, Karolinska Institute, Stockholm; and Söder Hospital, Karolinska Institute, Stockholm, Sweden). Risk assessment in patients with acute myocardial infarction treated with thrombolytic therapy. J Intern Med 2001; 249: 527–537.

Objective. Several noninvasive methods have prognostic information regarding mortality and new coronary events after an acute myocardial infarction (AMI). The practical for clinical decision‐making in the immediate postmyocardial infarction (MI) period is, however, less evident. We investigated consecutive patients with AMI treated with thrombolysis to further clarify this issue.

Design. A total of 100 patients (27% women) aged 64 ± 9 years (mean ± SD) were studied. Risk assessment based on a clinical score system, myocardial perfusion scintigraphy single photon emission computed tomography (SPECT) at rest and during adenosine stress, echocardiography, radionuclide angiography, symptom‐limited exercise stress test, and 24‐h Holter ECG recording with ST‐analysis and analysis of heart rate variability (HRV) were performed 5–8 days after hospital admission. Mortality, nonfatal reinfarction, and the need for revascularization were followed during 12 months.

Setting. A university hospital.

Results. A total of 6 patients died, seven had a nonfatal reinfarction, and 23 were revascularized. Inability to perform an exercise test (P=0.004) and an ejection fraction (EF) <40% (P=0.002) were the only parameters separating those who died from the survivors. No method could predict a nonfatal reinfarction. Patients suffering either death or nonfatal reinfarction had a clinical risk assessment score 2 points higher (8.8 vs. 6.7, P=0.05) than the group without such events. A positive symptom‐limited exercise stress test (P=0.027), ST‐depressions on Holter ECG (P=0.04), and reversibility on myocardial perfusion scintigraphy (P=0.029) predicted the need for revascularization.

Conclusion. Risk assessment based on clinical information, exercise stress testing, and an estimate of left ventricular function (e.g. via echocardiography) contribute with prognostic information in thrombolysed MI‐patients. Additional noninvasive investigations such as adenosine‐SPECT, analysis of HRV, and Holter‐monitoring do not add to these commonly available tools in risk stratification of subjects at low to medium risk.
Effects of thiazide‐ and loop‐diuretics, alone or in combination, on calcitropic hormones and biochemical bone markers: a randomized controlled study
Authors: Rejnmark L. , Vestergaard P. , Heickendorff L. , Andreasen F. , Mosekilde L.
Published: March 2003

Abstract. Rejnmark L, Vestergaard P, Heickendorff L, Andreasen F, Mosekilde L (Aarhus University, Aarhus, Denmark). Effects of thiazide‐ and loop‐diuretics, alone or in combination, on calcitropic hormones and biochemical bone markers: a randomized controlled study (Original study). J Intern Med 2001; 250: 144–153.

Objective. Diuretics are commonly used drugs that in addition to their effect on the cardiovascular system also affect calcium homeostasis and bone metabolism. We evaluated the effects of loop diuretics (LD) and thiazide diuretics (TD) on calcitropic hormones and biochemical bone markers.

Design. A total of 50 postmenopausal women were randomized to 7 days of treatment with either the TD bendroflumethiazide, the LD bumetanide, bendroflumethiazide plus bumetanide, or placebo. Blood and urine (24 h) were sampled on each day. Statistical inferences were made versus the concomitant changes in the placebo group.

Results. Bendroflumethiazide increased the tubular reabsorption of calcium (TRCa) (+0.46 ± 0.11%, P=0.009), plasma levels of parathyroid hormones (PTH) (+24 ± 10%, P=0.06), and 1,25(OH)2D (+12 ± 6%, P=0.03). Bumetanide decreased the TRCa (–0.5 ± 0.1%, P=0.01) and increased plasma PTH and 1,25(OH)2D levels (+27 ± 9%, P=0.02 and +36 ± 12%, P=0.006, respectively). Treatment with either of the drugs did not alter plasma calcium, osteocalcin, bone alkaline phosphatase (bone‐ALP) or urinary NTx/creatinine ratio. However, treatment with both drugs caused an increased plasma calcium level (+2.7 ± 1.0%, P=0.007) and decreased plasma levels of bone‐ALP (–21 ± 3%, P=0.001), osteocalcin (–6 ± 3%, P=0.03), and urinary NTx/creatinine ratio (–39 ± 6%, P=0.001).

Conclusion. Calcium homeostasis and bone metabolism are to a major degree influenced by diuretic treatment. Surprisingly, LD and TD exerted a similar effect on calcitropic hormones despite their opposite effects on the renal calcium excretion. In clinical practice, treatment with diuretics has to be considered as a cause of parathyroid stimulation.
High‐dose intravenous immunoglobulin in the treatment of acute myocarditis. A case report and review of the literature
Authors: Tedeschi A. , Airaghi L. , Giannini S. , Ciceri L. , Massari F. M.
Published: March 2003

Abstract. Tedeschi A, Airaghi L, Giannini S, Ciceri L, Massari FM (IRCCS Ospedale Maggiore Policlinico, Milan, Italy). High‐dose intravenous immunoglobulin in the treatment of acute myocarditis. A case report and review of the Literature. J Intern Med 2002; 251: 169–173.

A few reports have suggested the beneficial effect of high‐dose intravenous immunoglobulin (IVIG) in the treatment of acute myocarditis and cardiomyopathy. We describe a 49‐year‐old woman in which acute myocarditis was diagnosed on the basis of clinical and echocardiographic findings. Conventional treatment with captopril and frusemide was administered; intravenous heparin and, subsequently, oral anticoagulants were added because of the appearance of an apical thrombus. On the fifth day of hospitalization, treatment with high‐dose (400 mg kg−1 day−1) IVIG was started and prosecuted for 5 days. A dramatic improvement of clinical conditions was observed, with increase of the left ventricular ejection fraction (LVEF) from 30% to 75% within 1 week. One year after the diagnosis the patient is in good health, with steady normal LVEF. The rapid recovery, which was immediately subsequent to the administration of high‐dose IVIG, suggests that this kind of treatment has been effective in our patient with acute myocarditis.
The cost‐effectiveness of ramipril in the treatment of patients at high risk of cardiovascular events: a Swedish sub‐study to the HOPE study
Authors: Björholt I. , Andersson F. L. , Kahan T. , Östergren J.
Published: March 2003

Abstract. Björholt I, Andersson FL, Kahan T, Östergren J (AstraZeneca Sverige AB, Mölndal, Sweden/Institute of Surgical Sciences, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden; AstraZeneca R & D Lund, Lund, Sweden; Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden; and Karolinska Hospital, Stockholm, Sweden) The cost‐effectiveness of ramipril in the treatment of patients at high risk of cardiovascular events: a Swedish sub‐study to the hope study. J Intern Med 2002; 251: 508–517.

Objective. To evaluate if long‐term treatment with ramipril is cost‐effective in patients at high risk of cardiovascular events.

Design. Randomized double‐blind and placebo controlled. Information was gathered prospectively for a number of direct medical, direct nonmedical and indirect costs.

Setting and subjects. This is a sub‐study to the Heart Outcomes Prevention Evaluation (HOPE) study performed in Swedish patients. All Swedish centres (19; n= 554) were invited to take part and 18 centres agreed to do so (n=537). The patients were managed in a specialist setting with a mean follow‐up period of 4.5 years.

Main outcome measures. The number of life‐years saved was derived from the global HOPE study (n=9297) and subsequently the estimated life expectancy of those who completed the clinical study alive was added to the calculation. Direct medical costs related to cardiovascular disease only were considered in the primary analysis, whilst all kinds of costs and costs for all kinds of diseases were included in subsequent analyses. The cost of added years of life, according to the future cost method, was included in sensitivity analyses.

Results. The cost per life‐year gained was SEK 16 600 (Euro 1940) when direct medical costs for cardiovascular reasons only were considered and SEK 45 400 (Euro 5300) when direct medical costs for all diseases were considered. The corresponding costs when direct nonmedical and indirect cost were added to the estimate were SEK 16 100 (Euro 1880) and SEK 54 600 (Euro 6380), respectively. When the future cost method was applied, the cost per life‐year gained was SEK 208 300 (Euro 24 300).

Conclusion. Ramipril is highly cost‐effective in the treatment of patients at high risk of cardiovascular events.
Exacerbated chronic obstructive pulmonary disease: a frequently unrecognized condition
Authors: INCALZI R. ANTONELLI , FUSO L. , SERRA M. , BASSO S. , CAROSELLA L. , TRAMAGLINO L. M. , PISTELLI R. , CARBONIN P.
Published: March 2003

Abstract. Incalzi RA, Fuso L, Serra M, Basso S, Carosella L, Tramaglino LM, Pistelli R, Carbonin P. (Department of Geriatrics and Department of Respiratory Physiology, Catholic University, Rome, Italy). Exacerbated chronic obstructive pulmonary disease: a frequently unrecognized condition. J Intern Med 2002; 252: 48–55.

Objectives. To assess to which extent exacerbated chronic obstructive pulmonary disease (COPD) remains unrecognized in the emergency department, which factors account for misdiagnosis and which are the effects of misdiagnosis on patient's management.

Design. Retrospective study and stratified random sampling method as selection criterion.

Setting. University Hospital.

Subjects. Eighty patients representative of those discharged from the wards of medicine with a diagnosis of exacerbated COPD and 72 having a discharge diagnosis of coronary artery disease (CAD) were studied.

Main outcome measures. Degree of concordance between admission and discharge diagnosis; presenting symptoms and signs of patients correctly or incorrectly classified on admission; impact of diagnostic procedures carried out by the physician on call on patient's management.

Results. The correct diagnosis was missed on admission in 13/80 COPD and 3/72 CAD patients (χ2: 5.87, P=0.015). The prevalence of the following presenting features distinguished the 67 COPD patients who were correctly classified on admission from the remaining 13: severe weakness (21 vs. 10, χ2: 9.53, P=0.002), dyspnea (60 vs. 3, χ2: 28.75, P < 0.001), and limb oedema (14 vs. 6, χ2: 3.70, P=0.054). Critical hypoxemia was diagnosed and treated only after admission in 19 COPD patients.

Conclusions Exacerbated COPD frequently escapes recognition in the emergency room, mainly if severe weakness and limb oedema are its presenting features. Arterial blood gas analysis is not systematically performed in the emergency room and, consequently, oxygen therapy is either not administered or given to selected COPD patients on an empirical basis.
Evolution and spread of antibiotic resistance
Authors: Normark B. Henriques , Normark S.
Published: March 2003

Abstract.  Antibiotic resistance is a clinical and socioeconomical problem that is here to stay. Resistance can be natural or acquired. Some bacterial species, such as Pseudomonas aeruginosa, show a high intrinsic resistance to a number of antibiotics whereas others are normally highly antibiotic susceptible such as group A streptococci. Acquired resistance evolve via genetic alterations in the microbes own genome or by horizontal transfer of resistance genes located on various types of mobile DNA elements. Mutation frequencies to resistance can vary dramatically depending on the mechanism of resistance and whether or not the organism exhibits a mutator phenotype. Resistance usually has a biological cost for the microorganism, but compensatory mutations accumulate rapidly that abolish this fitness cost, explaining why many types of resistances may never disappear in a bacterial population. Resistance frequently occurs stepwise making it important to identify organisms with low level resistance that otherwise may constitute the genetic platform for development of higher resistance levels. Self‐replicating plasmids, prophages, transposons, integrons and resistance islands all represent DNA elements that frequently carry resistance genes into sensitive organisms. These elements add DNA to the microbe and utilize site‐specific recombinases/integrases for their integration into the genome. However, resistance may also be created by homologous recombination events creating mosaic genes where each piece of the gene may come from a different microbe. The selection with antibiotics have informed us much about the various genetic mechanisms that are responsible for microbial evolution.
What cause of mortality can we predict by cholesterol screening in the Japanese general population?
Authors: Okamura T. , Kadowaki T. , Hayakawa T. , Kita Y. , Okayama A. , Ueshima H. ,   For the Nippon Data80 Research Group
Published: March 2003

Abstract.  Okamura T, Kadowaki T, Hayakawa T, Kita Y, Okayama A, Ueshima H (Shiga University of Medical Science, Shiga, Japan; Iwate Medical University, Morioka, Iwate, Japan). What cause of mortality can we predict by cholesterol screening in the Japanese general population? J Intern Med 2003; 253: 169–180.

Objective.  In a population with a markedly lower coronary mortality such as in Japan, the benefit of cholesterol screening may be different from Western populations. We attempted to assess the importance of cholesterol screening in Japan.

Design.  A 13.2‐year cohort study for cause‐specific mortality.

Setting.  Three hundred randomly selected districts throughout Japan in which the National Survey on Circulatory Disorders 1980 was performed.

Subjects.  A total of 9216 community dwelling persons aged 30 years and over, with standardized serum cholesterol measurement and without a past history of cardiovascular disease.

Results.  There were 1206 deaths, which included 462 deaths due to cardiovascular disease with 79 coronary heart diseases. Hypercholesterolemia (>6.21 mmol L−1) showed a significant positive relation to coronary mortality (relative risk; 2.93, 95% confidence interval; 1.52–5.63) but not to stroke. Although hypocholesterolemia (<4.14 mmol L−1) was significantly associated with an increased risk of liver cancer, noncardiovascular, noncancer disease and all‐cause mortality, these associations, except for liver cancer, disappeared after excluding deaths in the first 5 years of the follow‐up. The multivariate adjusted attributable risk of hypercholesterolaemia for coronary disease was 0.98 per 1000 person‐years, which was threefold higher than that of hypocholesterolemia for liver cancer: 0.32 per 1000 person‐years. The attributable risk percentage of hypercholesterolaemia was 66% for coronary heart disease.

Conclusion.  Similar to Western populations, it is recommended to provide screening for hypercholesterolaemia in Japan, especially for males, although its attributable risk for coronary disease might be small.
Visibility of objects in computer simulations of noisy micrographs
Authors: Bright  , Newbury  , Steel
Published: March 2003

Thresholds of visibility for objects in images with random pixel noise are predicted in terms of the signal‐to‐noise ratio. From trials with volunteers marking test images, we determined visibility thresholds of objects obscured by random pixel noise. The test images had objects with a variety of simple shapes and relatively little internal structure. Aside from the noise, the background of the test images was smooth and featureless. We extend the threshold signal‐to‐noise ratio measurements of Rose and others to a variety of object sizes and shapes. For objects with areas less than a disc subtending 2° at the eye, visibility depends on the averaged difference in intensity from background, the noise level and the number of pixels in the object. Visibility does not seem to depend on object shape.
Elongate cavities and skin–core structure in Nephila spider silk observed by electron microscopy
Authors: Frische  , Maunsbach  , Vollrath
Published: March 2003

Major ampullate silk fibres from the orb‐weaving spider Nephila madagascariensis were analysed by transmission electron microscopy. The fibres have a thin outer layer surrounding a column of apparently homogeneous material which contains elongate cavities orientated parallel to the silk fibre axis. The cavities appear similar to ‘elongate vacuolar droplets’ observed in the silk of Antheraea silkmoth larvae. The overall skin–core structure is probably the result of a rheological pattern originating in the two secreting regions recognized in Nephila silk glands; the cavities indicate material inhomogeneities.
The measurement of the amplitude point spread function of microscope objective lenses
Authors: Juškaitis  , Wilson
Published: March 2003

We present a simple method of directly measuring the complex amplitude point spread function of a microscope objective lens. The method is based on an optical fibre interferometer. Experimental results are presented for a high‐aperture water‐immersion objective lens.
Characterizing the local nitrogen environment at platelets in type IaA/B diamond
Authors: Brydson  , Brown  , Bruley
Published: March 2003

The nitrogen K‐electron energy‐loss near‐edge structure from {100} platelets of type IaA/B diamond has been modelled using multiple scattering theory. It is demonstrated that the available experimental results are consistent with nitrogen present as a substitutional donor impurity in a diamond‐like environment. The most plausible model is the dinitrogen substituted pair (A centre). Detailed comparison between the fine structure in electron energy‐loss spectra and theory confirms the previously published A centre model. A less plausible model is the singly substitutional nitrogen with one of the C–N bonds elongated by 12.5–15%. However, this site is paramagnetic, in apparent contradiction to experiment.
Ultrastructure of the frog retina after high‐pressure freezing and freeze substitution
Authors: Wilson  , Farmer  , Karwoski
Published: March 2003

In many types of tissue, high‐pressure freezing (HPF), followed by freeze substitution, can produce excellent ultrastructural preservation at depths over 10 times that obtained by other cryofixation techniques. However, in the case of neural tissue, the benefits of HPF have not been realized. In the present study, isolated frog (Rana pipiens) retina was sliced at a thickness of 150 or 350 μm, rapidly frozen in a Balzers HPM 010 high‐pressure freezer, and freeze substituted with 1% OsO4 and 0.1% tannic acid in acetone. Specially designed HPF chambers and specific freezing media (35% high‐MW dextran for 150‐μm slices or 15% low‐MW dextran for 350‐μm slices) were required for adequate freezing.

The quality of preservation after HPF was excellent throughout the retina in both the 150‐ and 350‐μm slices, compared with chemically fixed slices. Specifically, HPF resulted in better preserved cellular, mitochondrial and nuclear membranes in all retinal layers.

This is the first study to successfully cryofix all of the layers of the retina. The increased depths of adequate freezing achieved by HPF should facilitate various ultrastructural studies of retina, as well as of other CNS tissues, where preservation approaching that of the ‘native’ state is required.
An infra‐red light‐transmitting aperture controller for use in single‐cell fluorescence photometry
Authors: Mahaut‐Smith
Published: March 2003

Photometric techniques are commonly used to monitor the output from fluorescent indicators during the study of cellular signalling. At the single‐cell level, the region of interest is normally set by a variable aperture placed within the microscope emission pathway. The present study reports an improved aperture controller which adjusts the area for fluorescence measurement, whilst allowing objects throughout the field of view to be continuously monitored using infra‐red illumination. A rectangular aperture is selected by four 715‐nm long‐pass glass filters which block > 99.9% of the fluorescence emission at 480–600 nm. A 780‐nm long‐pass glass filter is used to provide infra‐red illumination which does not interfere with the fluorescence signal, yet is detectable by a standard CCD camera. This allows detection of morphological events throughout the field of view and facilitates manipulation of extracellular pipettes, without interruption to a single‐cell fluorescence recording. The infra‐red light‐transmitting controller is suitable for use with a range of other fluorescent indicators, including those routinely used to detect Ca2+, Cl−, Na+ and pH. Data are presented which demonstrate the use of this controller to measure ADP‐evoked [Ca2+]i increases in single human erythroleukaemia cells loaded with the Ca2+ indicator fura‐2.
Application of X‐ray element mapping across the lichen–rock interface
Authors: Williamson  , McLean  , Purvis
Published: March 2003

The application of element mapping in the scanning electron microscope with electron probe microanalysis across the lichen–rock interface is described with reference to Trapelia involuta growing on a granite substratum. The preparation of samples containing both organic and mineral components required the development of specialized techniques to maintain both chemical and structural integrity at the 2 μm resolution of the X‐ray element maps. X‐ray element maps show the distribution of entrained rock particles at the lichen–rock interface and chemical localization which is strongly related to anatomical structure for the essential elements S, Fe, Ca, Na, K and P. The ability to map element distribution across the lichen–rock interface has wide‐ranging potential applications in studies such as the biodeterioration of buildings and monuments and the mobilization and uptake of toxic elements from contaminated substrata.
Estimating surface area by the isotropic fakir method from thick slices cut in an arbitrary direction
Authors: KubÍnová  , JanáČek
Published: March 2003

The proposed fakir method for estimating surface area is based on counting the intersections between the surface lying within a thick slice, and an isotropic spatial grid consisting of a combination of linear probes called fakir probes. An unbiased procedure using a directly randomized spatial grid rather than sections with randomized directions is presented. The method is applicable if perfectly registered serial sections of the surface are available in a thick slice while the direction of the slice can be arbitrary. The efficiency of the fakir method using different arrangements of orthogonal triplets of fakir probes is evaluated and it is shown that mutually shifted probes are superior to non‐shifted ones. The application software for interactive counting of intersections between computer‐generated fakir probes and the surface within the stack of digitized images is described and demonstrated by two examples: estimation of the surface area of individual tobacco cell chains using a confocal microscope, and estimation of the total area of exposed surface of mesophyll cells in a barley leaf using a wide‐field transmission microscope.
A comparison between the use of a high‐resolution CCD camera and 35 mm film for obtaining coloured micrographs
Authors: Entwistle
Published: March 2003

In light microscopy, colour CCD cameras are now capable of generating image data sets that contain more information than can be captured with slow 35 mm colour reversal film. The resolution of colour CCD cameras with a high density of sensor elements ( 3300 × 2200 per channel of colour) is equivalent to that of slow 35 mm colour film over typical fields of view for objectives with a wide range of magnifications and numerical apertures. The contrast that can be achieved in images derived from the data sets obtained with colour CCD cameras far exceeds that found with film and can exceed that of human vision. Finally, the data sets collected with high‐resolution colour CCD cameras are capable of being displayed at a wide range (four‐fold) of different magnifications easily and interchangeably. Consequently, the combination of a data set that describes a relatively large field of view with one or two data sets that describe specific details taken with an eight‐fold increase in magnification are all that is necessary to describe the salient features of the vast majority of stained specimens examined with transmitted light microscopy.
Star length distribution: a volume‐based concept for the characterization of structural anisotropy
Authors: Smit  , Schneider  , Odgaard
Published: March 2003

Determination and quantification of anisotropy is of great interest in research fields dealing with physical structures or surface textures. In this paper, a volume‐based method is presented, which essentially determines the mean object length in a certain direction for a typical point within a structure or texture. The mean object lengths for all orientations together form the so‐called star length distribution (SLD). The validity and the accuracy of the SLD method are investigated, and illustrated by applying it to trabecular bone. By using a line sampling algorithm, the relation with other anisotropy measures could be studied analytically. Preliminary tests suggest that with SLD a more exact description of the mechanical properties of porous structures may be obtained than with other anisotropy measures. However, due to possible secondary orientations that become apparent with SLD, a fabric tensor must be of rank higher than two in order to properly describe an orthogonal structure mathematically.
An optical method for recording the activity of single transporters in membrane patches
Authors: Tschödrich‐Rotter  , Peters
Published: March 2003

We have previously introduced an optical technique for recording the transport of fluorescent substrates by single membrane transporters. Referred to as optical single‐transporter recording (OSTR), the method was restricted to cases in which membrane transporters occurred at extremely small densities, namely at one or a few transporters per cell. Here we describe the extension of OSCR from whole cells harbouring a small number of transporters to small membrane patches containing transporters at normal densities. A technique was developed for firmly attaching cells to isoporous filters, i.e. very thin transparent sheets containing homogeneous populations of cylindrical pores. The flux of fluorescent transport substrates across the tiny membrane pieces spanning the filter pores was measured by scanning microphotolysis, a combination of fluorescence microphotolysis and confocal laser scanning microscopy. The technique was tested by attaching erythrocytes to filters containing pores of 1.2, 2.0 or 3.0 μm diameter. After treating filter‐attached erythrocyte membranes with streptolysin O, the transport of the fluorescent protein B‐phycoerythrin through single streptolysin O pores was observed. From the flux data the functional radius of the streptolysin O pore was derived to be 12.5 ± 0.9 nm, in very good agreement with previous electron microscopic estimates. The new technique features a number of unique properties: (i) the size of the membrane patch can be chosen within wide limits according to transporter density, (ii) transport can be recorded on many membrane patches in parallel, (iii) both influx and efflux may be analysed employing either photobleaching of fluorescent or photorelease of caged nonfluorescent substrates, (iv) two or more transport substrates may be monitored simultaneously. The new technique can be used, for instance, for analysing the activity of protein/particle pumps, a membrane transport domain not previously accessible to a single‐transporter analysis.