bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipoprotein(a) and cholesterol levels act synergistically and apolipoprotein A‐I is protective for the incidence of primary acute myocardial infarction in middle‐aged males. An incident case–control study from Sweden
Authors: Dahlén  , Weinehall  , Weinehall  , Stenlund  , Jansson  , Hallmans  , Huhtasaari  , Wall
Published: March 2003

Abstract.Dahlén GH, Weinehall L, Stenlund H, Jansson J‐H, Hallmans G, Huhtasaari F, Wall S (Umeå University, Umeå; Skellefteå County Hospital; and Luleå‐Boden County Hospital, Sweden). Lipoprotein(a) and cholesterol levels act synergistically and apolipoprotein A‐I is protective for the incidence of primary acute myocardial infarction in middle‐aged males. An incident case–control study from Sweden.J Intern Med1998;244: 425–30.

Objective

To further establish the importance of total plasma apolipoprotein A‐I and lipoprotein(a) in the prediction of primary acute myocardial infarction (AMI) in men.

Design

An incident case–control study.

Setting

The study was nested within the Västerbotten Intervention Program (VIP) and the Northern Sweden MONICA cohorts.

Subjects

A total of 62 male AMI cases and 124 matched controls, randomly selected from the study cohorts.

Results

In multivariate logistic regression, significant odds ratios (OR) were found for Lp(a) above 200 mg L−1, apo A‐I below the mean value (1136 mg L−1) and total cholesterol (TC) above 7.8 mmol L−1. TC interacted significantly with Lp(a); for Lp(a) above 200 mg L−1and TC below 6.5 mmol L−1, OR = 5.6; for Lp(a) above 200 mg L−1and TC above 6.5 mmol L−1, OR = 12.6. To evaluate the potential effect of reducing high levels of Lp(a) or TC on the incidence of AMI in males, the attributable risk percentage (ARP) was calculated when interaction between the two variables was present. ARP is 31% for Lp(a) and 21% for TC, implying that 31% of the cases are due to high Lp(a) and 21% of the cases are due to high TC levels.

Conclusions

In the Swedish male population, total apo A‐I in plasma is a protective factor and a plasma Lp(a) level above 200 mg L−1is a risk factor for AMI in males. A TC level above 6.5 mmol L−1increased the risk of AMI if the Lp(a) level was above 200 mg L−1, suggesting Lp(a) to be useful in identifying high risk individuals needed to be treated.
Plasma leptin levels are associated with abnormal fibrinolysis in men and postmenopausal women
Authors: Söderberg S. , Olsson T. , Eliasson M. , Johnson O. , Ahrén B.
Published: March 2003

Abstract. Söderberg S, Olsson T, Eliasson M, Johnson O, Ahrén B (Umeå University Hospital, Luleå County Hospital and Lund University, Malmö, Sweden). Plasma leptin levels are associated with abnormal fibrinolysis in men and postmenopausal women. J Intern Med 1999; 245: 533–543.

Background. Leptin is a crucial mediator of satiety signals and energy balance, and its circulating levels are increased in obesity. It has recently been shown that plasma leptin levels in humans correlate with circulating insulin and to insulin secretion. This indicates that leptin may be an important link in metabolic consequences of the insulin resistance syndrome. Whether this includes abnormalities in fibrinolysis has not been studied.

Methods and results. Healthy subjects (n = 165; 85 men and 80 women) from the Northern Sweden MONICA population were investigated. Anthropometric measurements, oral glucose tolerance tests and sampling for plasma leptin, lipids, fibrinogen and fibrinolytic variables were made. Leptin levels were 342% higher in women than in men and were in both sexes strongly correlated to body mass index (BMI). After adjustments for age and BMI, leptin levels correlated significantly to pre/post glucoseload insulin levels in both sexes. After further adjustment for baseline insulin levels, leptin levels were in males significantly associated with increased waist circumference (P < 0.001), low HDL cholesterol (P < 0.05), low tPA activity (P < 0.01) and high PAI‐1 activity (P < 0.001). In postmenopausal females, a significant association between leptin and low tPA activity/high PAI‐1 activity was seen after adjustment for age and BMI (P < 0.05).

Conclusions. Circulating levels of leptin are associated with components of the insulin resistance syndrome, including defective fibrinolysis, in men and postmenopausal women. This suggests that leptin may be involved in the mediation of consequences of insulin resistance.
Mitochondrial medicine – recent advances
Authors: Graff C. , Clayton D. A. , Larsson N.‐G.
Published: March 2003

Mitochondria contain the respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce the main part of cellular energy in the form of ATP. Mitochondrial DNA (mtDNA) encodes essential subunits of the respiratory chain and is thus critical for maintaining cellular energy production. The first pathogenic mtDNA mutations were reported in 1988, and today more than 50 disease‐causing mtDNA mutations have been identified. In addition, mtDNA mutations have been implicated in ageing and in common disorders such as diabetes mellitus, heart failure and Parkinson’s disease. This review will summarize recent advances in the rapidly expanding field of mitochondrial medicine.
Aetiology of fever in patients with acute stroke *
Authors: Georgilis K. , Plomaritoglou A. , Dafni U. , Bassiakos Y. , Vemmos K.
Published: March 2003

Georgilis K, Plomaritoglou A, Dafni U, Bassiakos Y, Vemmos K (University of Athens School of Medicine, ‘Alexandra’ Hospital, Athens, Greece; Harvard School of Public Health, Boston, Massachusetts; and the National School of Public Health, Athens, Greece). Aetiology of fever in patients with acute stroke. J Intern Med 1999; 246: 203–209.

Objective. Fever in patients with acute stroke is usually related to infectious complications. In some cases, a focus of infection cannot be identified, fever does not respond to empirical antibiotic treatment and is thought to be due to the central nervous system lesion. The aim of this study was to determine the frequency and origin of fever in patients with acute stroke and the characteristics associated with the presence of fever.

Design. A retrospective study of 36 months’ duration.

Setting. The study was carried out at ‘Alexandra’ Hospital, a tertiary care teaching centre in Athens, Greece.

Subjects. A total of 330 patients hospitalized for acute stroke from June 1992 until July 1994.

Results. In 37.6% of 330 patients, fever was noted; 22.7% had a documented infection and 14.8% had fever without a documented infection. In univariate analysis, older age was associated with the presence of fever (P = 0.001). The development of fever was associated with intracerebral haemorrhage versus ischaemic infarct (P < 0.001) and with the presence of mass effect (P < 0.001), transtentorial herniation (P < 0.001), intraventricular blood (P < 0.001), and larger size of ischaemic infarct (P = 0.0001) and of haemorrhage (P = 0.0002). Patients with fever had lower scores on admission on the Glasgow Coma Scale (P = 0.0001) and the Scandinavian Stroke Scale (P = 0.0001). The development of fever was associated with prior use of an invasive technique (P < 0.001) and more specifically with urinary catheterization (P < 0.001), but not with the presence of risk factors for infection. Patients with fever had a worse outcome assessed by the Modified Rankin Scale (P = 0.0001) and the Barthel Index (P = 0.0001). In multivariate analysis, age, Scandinavian Stroke Scale score and mass effect were found to be significantly associated with fever (P = 0.035, P = 0.0001 and P = 0.0004, respectively). Patients with fever without documented infection had an earlier onset of fever than those with infection (P = 0.0061). In a logistic regression analysis, the only factor predictive of fever without documented infection versus infection was earlier onset of fever
(P = 0.029).

Conclusion. Patients with acute stroke who develop fever are older, suffer severe stroke, their fever is associated with the use of invasive techniques, and they have a poor outcome. In patients with fever without a focus of infection, the only characteristic that is different from patients with known infection is earlier onset of fever.
Effects of age, gender and metabolic factors on endothelium‐dependent vasodilation: a population‐based study
Authors: Sarabi M. , Millgård J. , Lind L.
Published: March 2003

Abstract. Sarabi M, Millgård J, Lind L (University Hospital, Uppsala, Sweden). Effects of age, gender and metabolic factors on endothelium‐dependent vasodilation: a population‐based study. J Intern Med 1999; 246: 265–274.

Objectives. A progressive decline in endothelium‐dependent vasodilation (EDV) in the human forearm with age has previously been reported. The aim of this study was to evaluate the interplay between age, gender and metabolic factors on EDV in healthy subjects in a population‐based study.

Setting. Tertiary university hospital.

Subjects and design. Thirty‐six healthy men and 30 women, aged 20–69 years, underwent measurements of forearm blood flow (FBF) at rest and during local infusions of 2 and 4 µg min–1 of metacholine (evaluating EDV) and 5 and 10 µg min–1 of sodium nitroprusside (evaluating endothelium‐independent vasodilation, EIDV) and during reactive hyperaemia by venous occlusion plethysmography.

Results. Age was inversely related to EDV (r = – 0.41, P < 0.05 in men; r = – 0.61, P < 0.01 in women) and maximal FBF during reactive hyperaemia in both men and women. EIDV was significantly related to age in an inverse way in women only. EDV was more pronounced in females than in males before menopause (48 ± 3 SD years, 635 ± 186 vs. 502 ± 269% in males, P < 0.05), but similar in women and men thereafter (374 ± 141 vs. 370 ± 185% in men). The slope of the regression line for the relationship between age and EDV was flatter in premenopausal than in postmenopausal women (– 2.3 vs. – 6.4), whilst this slope was similar in younger and older men (– 5.5 vs. – 5.3). In multiple regression analysis, fasting blood glucose levels and the waist/hip ratio remained the only significant predictors of EDV in men (P < 0.01 for both), whilst age was the only significant independent predictor of EDV in women (P < 0.01).

Conclusion. The interplay between age and metabolic factors as determinants of endothelial function is different in healthy men and women.
Hyperhomocysteinaemia is not related to risk of distal somatic polyneuropathy: The Hoorn Study
Authors: Hoogeveen E. K. , Kostense P. J. , Valk G. D. , Bertelsmann F. W. , Jakobs C. , Dekker J. M. , Nijpels G. , Heine R. J. , Bouter L. M. , Stehouwer C. D. A.
Published: March 2003

Abstract. Hoogeveen EK, Kostense PJ, Valk GD, Bertelsmann FW, Jakobs C, Dekker JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CDA (University Hospital Vrije Universiteit, Amsterdam). Hyperhomocysteinaemia is not related to risk of distal somatic polyneuropathy: The Hoorn Study. J Intern Med 1999; 246: 561–566.

Objective. Distal somatic polyneuropathy is a major contributing factor in the pathogenesis of chronic foot infections and ulcers, and may lead to lower limb amputations. Both metabolic and vascular abnormalities may contribute to the development of impaired nerve function. We therefore assessed the association between hyperhomocysteinaemia, a risk factor for cardiovascular disease, and polyneuropathy.

Design, setting and subjects. We studied an age‐, sex‐ and glucose‐tolerance‐stratified random sample of a 50‐ to 75‐year‐old general Caucasian population in the Hoorn Study (N = 629). Any polyneuropathy (N = 95) was defined as the absence of at least two of the three following sensory modalities or reflexes of either foot: light touch sense, ankle reflex and vibration sensation. Definite polyneuropathy (N = 25) was present if, in addition, the vibration perception threshold of the right big toe was abnormal.

Results. The prevalence of any polyneuropathy was 12.4% (33 of 266) in subjects with normal glucose tolerance (NGT), 12.6% (21 of 167) in those with impaired glucose tolerance (IGT), and 25.3% (41 of 162) in those with type 2 diabetes. The prevalence of definite polyneuropathy was 2.6% (7 of 266) in subjects with NGT, 2.4% (4 of 167) in those with IGT and 8.7% (14 of 161) in type 2 diabetic subjects. Polyneuropathy was associated with known risk factors such as diabetes, hyperglycaemia and body height. After adjustment for age, sex, HbA1c and hypertension, the odds ratio (95% CI) for any polyneuropathy per 5 µmol L–1 (about 1 SD) serum total homocysteine increment was 1.00 (0.72–1.39). After adjustment for age and sex, it was 0.62 (0.21–1.89) for definite polyneuropathy.

Conclusion. Although a weak relation (as judged from the confidence intervals) cannot be excluded, we conclude that hyperhomocysteinaemia is probably not related to risk of distal somatic polyneuropathy.
Relation between incidence of pneumonia and protective reflexes in post‐stroke patients with oral or tube feeding
Authors: Nakajoh K. , Nakagawa T. , Sekizawa K. , Matsui T. , Arai H. , Sasaki H.
Published: March 2003

Abstract. Nakajoh K, Nakagawa T, Sekizawa K, Matsui T, Arai H, Sasaki H (Tohoku University School of Medicine, Sendai, Japan). Relation between incidence of pneumonia and protective reflexes in post‐stroke patients with oral or tube feeding. J Intern Med 2000; 247: 39–42.

Objectives. Although attenuated protective reflexes have been implicated in the development of aspiration pneumonia, the relation between the incidence of pneumonia and the state of these reflexes has not been investigated. Furthermore, the role of feeding tube placement in preventing pneumonia in patients with attenuated protective reflexes is unknown. We studied the relationship between the incidence of pneumonia and the state of cough and swallowing reflexes in post‐stroke patients with oral or tube feeding.

Design. The incidence of pneumonia was prospectively analysed for 1 year in three groups of post‐stroke patients on the basis of the following clinical conditions: oral feeding without dysphagia (n = 43); oral feeding with dysphagia (n = 48); and nasogastric tube feeding with dysphagia (n = 52). We also studied the incidence of pneumonia in bedridden patients with nasogastric tube feeding (n = 14). Before the start of the study, the swallowing and cough reflexes of each patient were measured. The swallowing reflex was evaluated according to latency of response, which was timed from the injection of 1 mL of distilled water into the pharynx through a nasal catheter to the onset of swallowing. The cough threshold of citric acid aerosols was defined as the concentration at which the patient coughed five times.

Results.; The incidence of pneumonia was observed in patients having both a latency of response longer than 5 s and a cough threshold for citric acid higher than a concentration of 1.35 (log mg mL–1). The incidence of pneumonia was significantly higher in patients with oral feeding than in those with tube feeding (54.3 vs. 13.2%, P < 0.001). In bedridden patients with tube feeding, the latency of response was longer than 20 s and no patient coughed at the highest concentration of citric acid. The incidence of pneumonia was 64.3% in such patients.

Conclusions. The state of protective reflexes had a significant relation to the incidence of pneumonia. Feeding tube placement may have a beneficial role in preventing aspiration pneumonia in mildly or moderately disabled post‐stroke patients with attenuated protective reflexes. Bedridden patients who were tube‐fed had the highest incidence of pneumonia.
Plasma total homocysteine levels in subjects with hyperinsulinemia
Authors: Bar‐On H. , Kidron M. , Friedlander Y. , Ben‐Yehuda A. , Selhub J. , Rosenberg I. H. , Friedman G.
Published: March 2003

Objectives. Hyperhomocysteinemia as well as insulin resistance are considered to be risk factors for the development of coronary artery disease. This study was aimed at determining whether any relationship between plasma insulin and glucose levels and total plasma homocysteine (tHcy) concentrations exists in a population based survey performed 10 years apart.

Design and Setting. A cross‐sectional study was undertaken during the years 1986–87 to examine risk factors for diabetes and for coronary artery disease (CAD) in the Jewish population of Jerusalem. Ten years later two groups of individuals were invited for re‐examination.

Subjects. Two groups of individuals were examined: the first one consisted of nondiabetic subjects (n = 86), who had hyperinsulinemia 10 years previously (at the first visit), the second group consisted of normoinsulinemic nondiabetic individuals (n = 265) who had initially normal glucose and insulin levels.

Main outcome measures. Metabolic, biochemical and anthropomorphic features were determined. Fasting and post load glucose, as well as insulin concentrations on fasting and 2 h post glucose load were measured at the first and second visits. Plasma tHcy and folic acid were determined only at the second visit.

Results. The results demonstrated a significant negative correlation between plasma tHcy levels and insulin levels at the second visit. No difference was found in folic acid levels between these two groups.

Conclusions. In general, hyperinsulinemia and hyperhomocysteinemia are both related to an increased incidence of CAD. In our population most of the subjects examined had tHcy levels within the normal range and only a few demonstrated very high levels. However, negative association between insulin levels and tHcy concentrations was found. Possible explanations for this finding are discussed.
Cortisol axis abnormalities early after stroke – relationships to cytokines and leptin
Authors: Johansson Å. , Ahrén B. , Näsman B. , Carlström K. , Olsson T.
Published: March 2003

Abstract. Johansson Å, Ahrén B, Näsman B, Carlström K, Olsson T (Umeå University Hospital, Umeå; Malmö University Hospital, Malmö; Karolinska Instituitet, Huddinge University Hospital, Huddinge, Sweden). Cortisol axis abnormalities early after stroke – relationships to cytokines and leptin. J Intern Med 2000; 247: 179–187.

Objective. To assess the relationships between circulating levels of proinflammatory cytokines and adrenocortical hormones and leptin early after stroke.

Design. Blood samples were collected four times daily the first two days after stroke, twice daily the next 4 days and four times at day 7. Cognitive function and functional outcome was measured at admittance and at day 7.

Setting. Consecutive inclusion of patients admitted to the stroke unit at Umeå University Hospital.

Subjects. Eight men and 4 women with acute stroke and 10 healthy volunteers.

Main outcome measures. Levels and diurnal variations of plasma proinflammatory cytokines interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α), serum adrenocortical hormones (cortisol and DHEA) and leptin, and MMSE, SSS, and ADL scores.

Results. A significant correlation was present between IL‐6 and cortisol levels the first two days after stroke (P < 0.05). In patients with a disturbed diurnal rhythm of cortisol, cortisol and leptin levels were increased (68% and 81% increase, respectively), whilst DHEA levels were unaltered. Half of the patients displayed an abnormal diurnal rhythmicity of leptin at the end of the week. Median TNF−α levels for the first two days after stroke also correlated to median leptin levels at the end of the week (P < 0.05). Median IL‐6 levels correlated to severity of paresis on days 1 and 7 and to MMSE scores on day 7 (P < 0.05).

Conclusions. Neuroendocrine disturbances are common and often profound early after stroke. Cytokines seem to be important modulators of these disturbances, including diurnal rhythmicity of cortisol and leptin.
Autoantibodies to modified LDLs and other phospholipid–protein complexes as markers of cardiovascular diseases
Authors: Vaarala O.
Published: March 2003

Abstract. Vaarala O (National Public Health Institute, 00300 Helsinki, Finland). Autoantibodies to modified LDLs and other phospholipid–protein complexes as markers of cardiovascular diseases (Minisymposium). J Intern Med 2000 247: 381–384.

Recent studies have suggested that antiphospholipid antibodies contribute to the development of atherothrombosis by enhancing atherogenesis and/or by interfering with blood coagulation. The antigenic targets of antiphospholipid antibodies are cardiolipin, oxidized LDL, β2‐glycoprotein I, or prothrombin. Oxidized LDL and β2‐glycoprotein I are found in the atherosclerotic plaque and antibodies to these proteins enhance in vitro the accumulation of modified LDL into macrophages. Autoantibodies binding to modified LDL, cardiolipin and prothrombin have been associated with atherosclerosis and its thrombotic complications in sero‐epidemiological studies. These autoantibodies can be used as markers of atherosclerosis but their possible pathogenic role in the athero‐ and thrombogenesis needs further studies.
Chlamydia pneumoniae in atherosclerosis
Authors: Saikku P.
Published: March 2003

Abstract. Saikku P (National Public Health Institute, Oulu, Finland). Chlamydia pneumoniae in atherosclerosis (Minisymposium). J Intern Med 2000; 247: 391–396.

Chlamydia pneumoniae is currently the infectious agent most often associated with the inflammation found in atherosclerosis. The seroepidemiological association and the actual presence of pathogen in lesions has been confirmed in numerous studies, in which technical difficulties seem to be the only limitation. Besides animal experiments and intervention trials, we need information of possible pathogenic mechanisms. Recently, several studies have suggested mechanisms by which C. pneumoniae infection could participate in the development of atherosclerosis.
IL‐6 and IL‐1 receptor antagonist in stable angina pectoris and relation of IL‐6 to clinical findings in acute myocardial infarction
Authors: Gabriel A. S. , Ahnve S. , Wretlind B. , Martinsson A.
Published: March 2003

Abstract. Gabriel AS, Ahnve S, Wretlind B, Martinsson A (Karolinska Institute and Huddinge University Hospital, Stockholm, Sweden). J Intern Med 2000; 248: 61–66.

Objectives. To determine if increased inflammatory activity, as reflected by interleukin‐6 (IL‐6) and interleukin‐1 receptor antagonist (IL‐1ra) levels, is present in patients with stable angina pectoris and if IL‐6 levels on admission to the coronary care unit in patients with acute myocardial infarction (AMI) are related to heart failure and fever response.

Subjects and methods. We studied 28 patients with stable angina pectoris enrolled for coronary angiography, and compared them with sex‐ and age‐matched controls. Thirty‐four patients with AMI were studied and samples for determination of IL‐6 levels were taken on admission within 36 h of onset of symptoms. IL‐6 and IL‐1ra were determined in serum by enzyme immunoassay.

Results. Levels of IL‐6 and IL‐1ra were higher in patients with stable angina pectoris than in controls (mean 4.6 ± 3.6 vs. 3.0 ± 2.9 ng L–1, P < 0.03, and 774 ± 509 vs. 490 ± 511 ng L–1, P < 0.01, respectively). IL‐6 and IL‐1ra levels were not related to angiographic findings. IL‐6 levels were high in patients with AMI (38.9 ± 75.6 ng L–1). Patients with prolonged fever (duration > 4 days) had higher IL‐6 levels (94.7 ± 138.2 vs. 21.7 ± 29.7 ng L–1, P < 0.05). IL‐6 levels were not related to heart failure.

Conclusions. Our results indicate that increased inflammatory activity is present not only in acute coronary syndromes, but also in a chronic form of ischaemic heart disease, giving further evidence for a central role of inflammatory processes in coronary artery disease. With regard to AMI, we found increased inflammatory activity in patients with prolonged fever.
Intraoperative haemorrhage associated with the use of extract of Saw Palmetto herb: a case report and review of literature
Authors: Cheema P. , El‐Mefty O. , Jazieh A. R.
Published: March 2003

Abstract. Cheema P, El‐Mefty O, Jazieh AR (University of Arkansas for Medical Sciences, Arkansas and University of Cincinnati, Ohio, USA). Intraoperative haemorrhage associated with the use of extract of Saw Palmetto herb: a case report and review of literature. J Intern Med 2001; 250: 167–169.

The significant increase in the use of alternative medicine in general and the herbal and dietary supplement in particular represents a challenge to the health care professionals. Because of their unregulated use, physicians are encountering increasing numbers of toxicities and untoward events. We report a case of severe intraoperative haemorrhage in a patient who was taking the herb Saw Palmetto. His bleeding time which was prolonged, normalized few days after he stopped the herb. This case should increase the awareness of physicians to such possible complications and encourage them to enquire thoroughly about the use of any dietary supplement in all their patients.
Atrial fibrillation – where do we stand today?
Authors: Olsson S. B.
Published: March 2003

Olsson SB (University Hospital, Lund, Sweden). Atrial fibrillation – where do we stand today? J Intern Med 2001; 250: 19–28.

The basic underlying mechanisms behind atrial fibrillation (AF), the most abundant therapy demanding cardiac dysrhythmia, have until recently being largely unknown. Once established, AF is not only self‐perpetuating but also self‐destructive, prompting rapid treatment against possible initiating mechanisms. Recent observations reveal that the ectopic beats, initiating AF, often originate in the walls of the pulmonary veins and that the deterioration of the ectopic impulse to AF may be linked to an impaired inferoposterior interatrial conduction. The underlying mechanisms behind these functional defects are still obscure. The observations has however, permitted evaluation of new types of treatment, directly interfering with the newly verified findings.
Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women
Authors: Gužič‐Salobir B. , Keber I. , Seljeflot I. , Arnesen H. , Vrabič L.
Published: March 2003

Abstract. Gužič‐Salobir B, Keber I, Seljeflot I, Arnesen H, Vrabič L (University Medical Centre, Ljubljana, Slovenia; Ullevaal University Hospital, Oslo, Norway; and Novo Nordisk A/S, Ljubljana, Slovenia). Combined hormone replacement therapy improves endothelial function in healthy postmenopausal women. J Intern Med 2001; 250: 508–515.

Objectives. Large scale epidemiological studies suggest that hormone replacement therapy (HRT) reduces cardiovascular events in postmenopausal women. Improvement in endothelial function may contribute to this protective effect.

Design. In a prospective, double blind study, 61 healthy postmenopausal women were randomized to receive either oral continuous combined HRT [oestradiol 2 mg and norethisterone acetate (NETA) 1 mg per day] or placebo. Endothelial function, assessed by flow‐mediated vasodilation (FMD) of the brachial artery and expression of soluble endothelial cell adhesion molecules (CAM) were determined before, after 3 and 6 months of therapy.

Results. The FMD was significantly improved in women on combined HRT (from 5.97% to 10.94% after 3 months and to 10.58% after 6 months; both P < 0.01 versus baseline values) and did not change in the placebo group (6.92% at baseline, 5.86% after 3 and 6.26% after 6 months). After 3 months of combined HRT, significant decreases of 24.6% for E‐selectin and 13.9% for intercellular adhesion molecule‐1 (ICAM‐1) were observed (both P < 0.01 versus baseline values) and were sustained after 6 months of therapy, whilst no differences emerged in the placebo group.

Conclusions. Oestradiol and norethisterone acetate improve endothelial function by both enhancing FMD and reducing the levels of soluble E‐selectin and ICAM‐1 in healthy postmenopausal women.
Tobacco use, cancer causation and public health impact
Authors: Kuper H. , Adami H.‐O. , Boffetta P.
Published: March 2003

Abstract. Kuper H, Adami H‐O, Boffetta P (University College London, Torrington Place, London, UK; Karolinska Institutet, Stockholm, Sweden; and International Agency for Research on Cancer, Lyon, France). Tobacco use, cancer causation and public health impact. J Intern Med 2002; 251: 455–466.

This review describes global patterns of tobacco use and the mechanisms by which tobacco use is involved in carcinogenesis. A second part will discuss the association between tobacco use and risk of specific cancer types. To bacco use has traditionally been a practice of high‐income countries, but it has recently been taken up in low‐income countries and it is particularly common in men. A wide variety of tobacco products exist, of which cigarettes are most frequently consumed. Tobacco products contain more than 50 established or identified carcinogens and these may increase risk of cancer by causing mutations that disrupt cell cycle regulation, or through their effect on the immune or endocrine systems. Certain factors such as genes, diet and environmental exposures may alter susceptibility to cancer in tobacco users. Today at least 15% of all cancers are estimated to be attributable to smoking, but this figure is expected to increase because of the uptake of tobacco use in low‐income countries.
A new classification tool for clinical differentiation between haemorrhagic and ischaemic stroke
Authors: Efstathiou S. P. , Tsioulos D. I. , Zacharos I. D. , Tsiakou A. G. , Mitromaras A. G. , Mastorantonakis S. E. , Pefanis A. V. , Mountokalakis T. D.
Published: March 2003

Abstract. Efstathiou SP, Tsioulos DI, Zacharos ID, Tsiakou AG, Mitromaras AG, Mastorantonakis SE, Pefanis AV, Mountokalakis TD (Sotiria Hospital, Athens, Greece). A new classification tool for clinical differentiation between haemorrhagic and ischaemic stroke. J Intern Med 2002; 252: 121–129.

Purpose. To develop a simple and reliable diagnostic tool for differentiation of cerebral infarction (CIF) from intracerebral haemorrhage (ICH) in order to aid clinicians to decide about starting antiplatelet therapy in settings where rapid access to computed tomography (CT) is lacking.

Methods. Thirty variables regarding each patient admitted with acute stroke were recorded and considered in a logistic regression analysis using ICH as end‐point (internal study). CT was used as the golden standard. The score derived was validated with data from the next consecutive stroke patients and was compared with the three preexisting scores (external validation study).

Results. Amongst 235 patients (119 males, mean age 70.6 ± 11.2 years) of the internal study, 43 (18.3%) had ICH. Four independent correlates of ICH were identified and used for the derivation of the following integer‐based scoring system: number of points=6 * (neurological deterioration within 3 h from admission) + 4 * (vomiting) + 4 * (WBC > 12 000) + 3 * (decreased level of consciousness). In the external study [168 patients, 85 males, mean age 70.2 ± 10.8 years, 31 (18.5%) with ICH], when the cut‐offs ≤3 points for CIF and ≥11 points for ICH were used, sensitivity, specificity, and positive and negative predictive values of the score for detection of stroke type were 97, 99, 97 and 99%, respectively; exceeding noticeably the three previously proposed systems.

Conclusions. The proposed model provides an easy to use tool for sufficiently accurate differentiation between haemorrhagic and nonhaemorrhagic stroke on the basis of information available to all physicians early after admission.
Effects of cigarette smoking or nicotine replacement on cardiovascular risk factors and parameters of haemorheology
Authors: Haustein K.‐O. , Krause J. , Haustein H. , Rasmussen T. , Cort N.
Published: March 2003

Abstract. Haustein K‐O, Krause J, Haustein H, Rasmussen T, Cort N (Institute of Nicotine Research and Smoking Cessation, Erfurt, Germany; and Pharmacia Consumer Healthcare, Helsingborg, Sweden). Effects of cigarette smoking or nicotine replacement on cardiovascular risk factors and parameters of haemorheology. J Intern Med 2002; 252: 130–139.

Objectives. Cigarette smoking causes cardiovascular (CV) disease, but the relative roles of nicotine and other components of tobacco smoke remain unclear. We investigated the effect of stopping smoking, by using nicotine replacement therapy (NRT), on haemorheology parameters.

Design. Open, parallel‐group trial (intervention group and control smokers).

Setting. Clinic within university department of pharmacology.

Subjects. One hundred and ninety‐seven males, aged 25–45 years, smoking >20 cigarettes per day.

Interventions. One hundred and sixty‐four subjects were instructed to stop smoking and received NRT for 12 weeks and 33 acted as controls. After 12 weeks, NRT was discontinued, and all subjects were followed‐up at 26 weeks. At the end of the study, the NRT group was divided into abstainers (self‐reported, verified by exhaled carbon monoxide <10 ppm) and relapsers, who were unable to remain abstinent.

Main outcome measures. Plasma viscosity, fibrinogen, erythrocyte deformability, reactive capillary blood flow, transcutaneous partial oxygen tension (tcpO2) and haematocrit, assessed at 4, 8, 12, and 26 weeks.

Results. After 6 months, plasma fibrinogen (9.95 vs. 8.24 μmol L–1 at baseline; P < 0.003), reactive capillary flow (t–pmax: 9.3 vs. 11.2 s at baseline; P < 0.005), and tcpO2 (50.4 vs. 34.9 mmHg at baseline; P < 0.0001) were significantly improved in abstainers, but changes in plasma viscosity and erythrocyte deformability were inconclusive. Other CV risk factors, such as haematocrit and white blood cell count, decreased to a greater extent in abstainers than in relapsers. Expired carbon monoxide concentrations reflected the changes in smoking and decreased in abstainers from 30.4 ppm at baseline to 4.2 ppm; P < 0.0001).

Conclusions. Smoking cessation improved CV parameters, and use of nicotine medications did not negate these improvements.
Significant predictors of poor prognosis in women aged ≤65 years hospitalized for an acute coronary event
Authors: Al‐Khalili F. , Svane B. , Janszky I. , Rydén L. , Orth‐Gomér K. , Schenck‐Gustafsson K.
Published: March 2003

Abstract.  Al‐Khalili F, Svane B, Janszky I, Rydén L, Orth‐Gomér K, Schenck‐Gustafsson K (Karolinska Hospital and Karolinska Institutet, Stockholm, Sweden). Significant predictors of poor prognosis in women aged ≤65 years hospitalized for an acute coronary event. J Intern Med 2002; 252: 561–569.

Objectives.  The aim of this study was to evaluate the importance of different clinical parameters predicting long‐term cardiac prognosis in younger women with an acute coronary event.

Design.  The Stockholm Female Coronary Risk Study is a follow‐up study in women ≤65 years.

Setting.  Patients were included between 1991 and 1994 from all 10 coronary care or intensive care units in the greater Stockholm area.

Subjects.  A total of 335 consecutive female patients hospitalized for an acute coronary event.

Main outcome measures.  Cardiac death and nonfatal myocardial infarction (AMI).

Results.  During the follow‐up period of 5 years there were 26 (8%) all cause deaths and 39 (12%) recurrent cardiac events. In the group that participated in the complete study, the following age adjusted parameters were found as strong predictors of adverse outcome: AMI as index event [Hazard Ratio (HR) 9.13, 95% CI 3.09–26.99], diabetes mellitus (HR 4.13, 95% CI 1.68–10.17), left ventricular dysfunction (HR 3.94, 95% CI 1.52–10.17), serum HDL cholesterol <1.0 mmol L−1 (HR 4.01, 95% CI 1.62–6.12), and serum triglycerides >2.0 mmol L−1 (HR 2.46, 95% CI 1.06–5.54). AMI as index event and diabetes mellitus were the most significant predictors in a multivariate statistical model. Diabetes mellitus was the strongest predictor when the analysis was repeated in the total patient cohort, integrating patients that did not participate in the extended investigations.

Conclusion.  Women aged ≤65‐year‐old hospitalized for an acute coronary event has a low rate of cardiac events during the following 5‐year period. Easily obtained clinical variables such as diabetes mellitus predict adverse prognosis and implicates a need for a more active diagnostic and treatment strategy.
Acupuncture versus placebo versus sumatriptan for early treatment of migraine attacks: a randomized controlled trial
Authors: Melchart D. , Thormaehlen J. , Hager S. , Liao J. , Linde K. , Weidenhammer W.
Published: March 2003

Abstract.  Melchart D, Thormaehlen J, Hager S, Liao J, Linde K, Weidenhammer W (Technical University, Munich, Germany; University Zurich, Switzerland; and Hospital for Traditional Chinese Medicine, Koetzting, Germany). Acupuncture versus placebo versus sumatriptan for early treatment of migraine attacks: a randomized controlled trial. J Intern Med 2003; 253: 181–188.

Objectives.  To investigate whether acupuncture is superior to placebo and equivalent to sumatriptan for the early treatment of an acute migraine attack.

Design.  Randomized, partly double‐blind (sumatriptan versus placebo) trial.

Setting.  Two hospitals in Germany (one specialized in traditional Chinese medicine and one in the treatment of headache).

Subjects.  A total of 179 migraineurs experiencing the first symptoms of a developing migraine attack.

Interventions.  Traditional Chinese acupuncture, sumatriptan (6 mg subcutaneously) or placebo injection.

Main outcome measure.  Number of patients in whom a full migraine attack (defined as severe migraine headache) within 48 h was prevented. In patients who developed a migraine attack in spite of early treatment, acupuncture and sumatriptan were applied a second time, whilst patients initially randomized to placebo received sumatriptan.

Results.  A full migraine attack was prevented in 21 of 60 (35%) patients receiving acupuncture, 21 of 58 (36%) patients receiving sumatriptan and 11 of 61 (18%) patients receiving placebo (relative risk of having a full attack 0.79 (95% CI, 0.64–0.99) for acupuncture versus placebo, and 0.78 (95% CI, 0.62–0.98) for sumatriptan versus placebo). Response to the second intervention in patients who developed a full attack was better with sumatriptan (17/31 patients who received sumatriptan twice and 37/46 patients who had had placebo first) than with acupuncture (4/31). The number of patients reporting side‐effects was 14 in the acupuncture group, 23 in the sumatriptan group and 10 in the placebo group.

Conclusions.  In this trial acupuncture and sumatriptan were more effective than a placebo injection in the early treatment of an acute migraine attack. When an attack could not be prevented, sumatriptan was more effective than acupuncture at relieving headache.
Plasma total homocysteine levels and prognosis in patients with previous premature myocardial infarction: a 10‐year follow‐up study
Authors: Retterstol L. , Paus B. , Bohn M. , Bakken A. , Erikssen J. , Malinow M. R. , Berg K.
Published: March 2003

Abstract. Retterstol L, Paus B, Bohn M, Bakken A, Erikssen J, Malinow MR, Berg K (University of Oslo; Ullevål University Hospital, Oslo; Akershus University Hospital, Norway; and Oregon Regional Primate Research Center Beaverton, OR, USA). Plasma total homocysteine levels and prognosis in patients with previous premature myocardial infarction: a 10‐year follow‐up study. J Intern Med 2003; 253: 284–292.

Objectives.  To explore plasma total homocysteine (tHcy) as a predictor of long‐term prognosis after premature myocardial infarction (MI).

Design.  Prospective cohort study.

Settings.  Akershus University Hospital.

Subjects.  A total of 247 patients (193 men and 54 women) in stable clinical phase after premature MI (males: first MI at age ≤55; females ≤60).

Main outcome measures.  The primary end‐point was total mortality and the secondary end‐point was cardiac death. The third end‐point was major cardiac events: a combination of cardiac death, MI and cardiac arrest.

Results.  After 10 years, 44 patients had died, 36 from cardiac causes. Major cardiac event occurred in 70 patients.

The relative risk for death of all causes increased 1.43 (95% CI, 1.08–1.88) per tHcy quartile (P for trend = 0.01), and was only modestly reduced after adjustment for age, ejection fraction, total cholesterol, C‐reactive protein, fibrinogen, smoking and hypertension to 1.37 (95% CI, 1.04–1.80) (P for trend = 0.03). Similar results were observed when cardiac death was used as the end‐point, but we observed no association between tHcy and the end‐point major cardiac event.

Conclusions.  Total homocysteine was an independent predictor of total and cardiac mortality in stable patients following premature MI. tHcy had no effect on major cardiac event in contrast to most other risk factors in this study. Thus, the mechanism(s) underlying the effects of homocysteine on coronary heart disease may differ from other risk factors.
Quantitative and qualitative characterization of aquatic iron oxyhydroxide particles by EF‐TEM
Authors: Mavrocordatos  , Perret
Published: March 2003

Electron energy‐loss spectroscopy (EELS) and elemental imaging under the energy‐filtered transmission electron microscope are powerful tools for the characterization of iron‐rich particles present in natural waters. Features present in EEL spectra (Fe‐M2,3Fe‐L2,3and O‐K ionization edges) of goethite (α‐FeOOH) have been studied with an energy filter operated at 80 keV to determine optimal quantification and elemental imaging of Fe‐rich natural aquatic particles in the 30–200 nm range of thickness. For quantitative aims, the Fe‐M2,3ionization edge cannot be used easily, but the Fe‐L2,3edge provides more accurate results owing to a better background extrapolation. The partial cross‐section of the Fe(III) M shell has been determined for iron oxide. The use of two‐windows (jump‐ratio) and three‐windows (background stripping) imaging methods is discussed in relation to the specimen thickness.
Defect formation in self‐assembling quantum dots of InGaAs on GaAs: a case study of direct measurements of local strain from HREM
Authors: JIN‐PHILLIPP  , PHILLIPP
Published: March 2003

The growth and defect structures in free‐standing self‐assembled In0.6Ga0.4As quantum dots (QDs) grown on (001) GaAs by solid source molecular beam epitaxy has been investigated. The QDs are elongated along [1¯ 1 0]. At a nominal thickness of eight monolayers defect complexes, associated with intrinsic stacking faults, have been generally observed on both sides of a QD in (1¯ 1 0) cross‐section. The total defect vector of such defect complexes is a/3 <111>. Local strain components on {111} slip planes in the QDs without defects have been measured directly from digitized high‐resolution electron microscopy images. The distortion on the two sets of {111} planes of a (1¯ 1 0) cross‐section is different owing to elastic relaxation. The results of strain measurements suggest that a 60° dislocation nucleates first on the set of {111} planes of higher contractive shear strain, i.e. (111) planes on the right side of the QDs, and (1¯ 1¯ 1) planes on the left side. A 30° partial dislocation forms subsequently on the other set of {111} planes, i.e. (1¯ 1¯ 1) planes on the right side of the QDs and (111) planes on the left side, when the 60° dislocation glides down towards the In0.6Ga0.4As/GaAs interface, as a result of the additional strain field of the 60° dislocation. The efficiency of the defect complexes in strain relaxation of the QDs has been shown by strain measurements in QDs with the presence of defects.
Cryo‐techniques applied to stratum corneum with description of a new sample holder for cryo‐scanning electron microscopy of freeze‐fractured samples
Authors: Hallegot  , Minondo  , Fiat
Published: March 2003

Stratum corneum structure greatly differs from that of the living epidermis and specific sample cryo‐preparation techniques have to be used. Practical aspects of these cryo‐techniques applied to stratum corneum are discussed. Emphasis is placed on scanning electron microscopy of cryo‐fixed samples. A new sample holder designed for cryo‐scanning electron microscopy of freeze‐fractured stratum corneum is described.
Electron diffraction from micro‐ and nanoparticles of hydroxyapatite
Authors: Suvorova  , Buffat
Published: March 2003

Hydroxyapatite (HAP) obtained from aqueous solutions under different conditions has been examined by high‐resolution transmission electron microscopy (HRTEM) and electron diffraction, including selected‐area electron diffraction (SAED) and microdiffraction. A Philips CM300 field‐emission gun electron microscope with a Schottky W/ZrO field‐emission tip and a spherical aberration constant of 0.65 mm was used at 300 kV. The HAP crystals had different sizes, ranging from a few nanometres to a few micrometres. Single‐crystal diffraction patterns have been obtained from the largest microcrystals using the conventional SAED technique. Assemblies of nanoparticles gave only broad diffuse rings. Nevertheless, microdiffraction with electron microprobes 3.5–10 nm in diameter clearly indicated the crystalline character of the nanoparticles in these assemblies. Experimental HRTEM images, Fourier transforms and calculated images exhibited the fine structure of the HAP crystals.
Microstructural characteristics of calcium hydroxyapatite/poly‐ l‐lactide based composites
Authors: Ignjatovic  , Plavsic  , Miljkovic  , Zivkovic  , Uskokovic
Published: March 2003

Besides its high osteoinductive properties, hydroxyapatite (HAp) exhibits a relatively low mechanical strength. In order to improve the mechanical properties and reliability of HAp based composites, the addition of selected polymers is highly recommended. The main objective of this work is to study the microstructural characteristics of HAp/poly‐ l‐lactide (PLLA) composites obtained by cold or hot processing. The composites were prepared from a mixture of a chloroform solution of poly‐
l‐lactide with granulated HAp. After elimination of chloroform by vacuum evaporation, dense compacts were obtained by cold or hot pressing. The pressing pressure ranged from 98.10 to 294.3 MPa for both cold and hot pressing. The hot pressing was performed in the temperature region 293–457 K for a time period of 15–60 min. Depending on the PLLA amount and the pressing procedure it is possible to obtain highly porous or nearly fully dense composites. The scanning electron microscopy examination of fracture as well as of free surfaces revealed that the final porosity and wetting are affected to a great extent by the synthesis conditions and amount of polymer added. An increase in temperature to 457 K for a longer period of time results in fully dense compacts. The formation of a nearly continuous polymer network that leads to the hardening of HAp has also been observed. However, it should be pointed out that some layers of HAp may be free of polymer film since PLLA penetrates more deeply into the porous HAp.
Unbiased and efficient estimation of the total number of terminal bronchiolar duct endings in lung: a modified physical disector
Authors: Beech  , Howard  , Reed  , Sibbons  , Van Velzen
Published: March 2003

A novel modification of the physical disector is described which was used to estimate the total number of terminal bronchiolar duct endings (TBDEs) in human infant lung. TBDEs are closed three‐dimensional space curves of complex shape that are inherently difficult to count from histological sections. However, careful consideration of the microanatomy of the terminal duct endings provides us with the opportunity to define a very simple and unbiased counting rule. To apply the rule in practice we also need to determine a suitable disector height. Owing to the complex shape of the TBDE we had no prior knowledge of what disector height would be suitable for counting the TBDE structures. Exhaustive serial sectioning of complete TBDE structures was carried out and showed that any disector height under 90 μm would give unbiased counts. A further empirical study was then undertaken to determine the most efficient disector height. This was found to be 50 μm.

The total number of TBDEs in the upper lobe of the right lung of six human infants aged between 13 and 25 weeks was also estimated. The estimates of numerical density obtained with our modification of the physical disector were multiplied by estimates of lung lobe volume obtained using Cavalieri's Principle. The total number of TBDEs in the lobes ranged from 15 323 to 57 768, with a mean of 40 306. The average coefficient of error of the number estimates was 19%, which was deemed precise enough given the biological coefficient of variation between TBDE number of 36%.