bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of systemic recombinant interferon‐alpha in Behcet's disease
Authors: Georgiou  , Monastirli  , Pasmatzi  , Gartaganis  , Goerz  , Tsambaos
Published: March 2003

Georgiou S, Monastirli A, Pasmatzi E, Gartaganis S, Goerz G, Tsambaos D (Departments of Dermatology and Ophthalmology, University of Patras, Greece and the Department of Dermatology, Heinrich‐Heine University of Düsseldorf, Germany). Efficacy and safety of systemic recombinant interferon‐alpha in Behcet's disease. J Intern Med 1998; 243: 367–72.

Objectives

To evaluate the therapeutic efficacy and safety of systemic recombinant interferon α‐2a (IFN ‐α) in patients with Behcet's disease (BD) and to determine the incidence of episodes in complete responders during the one‐year pretreatment period and follow‐up.

Design

An open clinical study.

Setting

Departments of Dermatology and Ophthalmology, University of Patras, Greece and Department of Dermatology, Heinrich‐Heine University of Düsseldorf, Germany.

Subjects

Twelve patients (aged 23–52 years) with active BD who had previously been unsuccessfully treated with systemic steroids and/or immunosuppressives.

Interventions

IFN‐α was administered subcutaneously at a dose of 6 × 106 IU per day 3 times per week for 2 months.

Main outcome measures

Change of area or number of mucocutaneous lesions, grading score for thrombophlebitis and ocular inflammation, haematological and biochemical parameters and number of episodes during the pretreatment period and the follow‐up. Evaluation of IFN‐α side effects.

Results

Nine patients (75.0%) revealed a complete remission, two (16.6%) a partial remission and one patient (8.3%) showed no response. During the follow‐up in five out of the nine complete responders (55.5%) no episodes of BD were seen, whereas, the other four patients (44.5%) had 1–2 episodes, as compared to 5–8 and 5–12 episodes, respectively, during the pretreatment period. An influenza‐like syndrome (fever, nausea and myalgias) appeared during the early phase of therapy in all (but one) patients. No patient had to discontinue IFN‐α because of intolerance.

Conclusions

Subcutaneous human recombinant interferon α‐2a appears to be an effective and fairly well tolerated therapy for BD.
Serum 25‐hydroxyvitamin D levels and bone mineral density in 16–20 years‐old girls: lack of association
Authors: Kristinsson J. Ö. , Valdimarsson Ö. , Sigurdsson  , Franzson  , Olafsson  , Steingrimsdottir
Published: March 2003

Kristinsson JÖ, Valdimarsson Ö, Sigurdsson G, Franzson L, Olafsson I & Steingrimsdottir L. (Reykjavik Hospital, University of Iceland, Reykjavik, Iceland). Serum 25‐Hydroxyvitamin D Levels and bone mineral density in 16–20 years old girls: lack of association. J of Intern Med 1998; 243: 381–88

In conclusion, our results indicate that the vitamin D requirements for normal bone mineral accrual in adolescent and young adult girls may be lower than presumed and suggest that calcium and phosphate concentrations in plasma may be regulated in this age group to some extent by other factors which needs to be further clarified. However, the important question of the effect of repeated, cyclical vitamin‐D nadir on bone mass in young people needs to be explored in a longitudinal survey.
Prophylactic splenectomy and cholecystectomy in mild hereditary spherocytosis: analyzing the decision in different clinical scenarios
Authors: Marchetti  , Quaglini  , Barosi
Published: March 2003

Marchetti M, Quaglini S, Barosi G (Laboratory of Medical Informatics, IRCCS Policlinico S. Matteo and the Department of Computer Science and Systems, University of Pavia, Pavia, Italy) Prophylactic splenectomy and cholecystectomy in mild hereditary spherocytosis: analyzing the decision in different clinical scenarios. J Intern Med 1998; 244: 217–26.

Objectives.Patients with mild hereditary spherocytosis (HS), i.e. with haemolysis without anaemia, have an increased risk of gallstone formation, erythroid aplasia and haemolytic crisis. Since the effect of prophylactic splenectomy on life expectancy has not been established, we conducted a decision analysis comparing prophylactic splenectomy and cholecystectomy with no surgery.

Design

.The available data on surgery and disease outcomes were modelled to estimate the effects of the different interventions on the quality‐adjusted life expectancy. The early phase outcomes depicted surgery‐related mortality and incorporated compliance and the adverse effects of prophylaxis against post splenectomy infections. The late phase outcomes were framed by a Markov cohort analysis.

Results

.For patients without gallstones, surgery was of no benefit. For those with gallstones the preferred strategies were found to be splenectomy and cholecystectomy before the age of 39 when asymptomatic, and before 52 when accompanied by occasional biliary colic. Cholecystectomy alone proved to be the preferred strategy in older patients with occasional biliary colic. For patients of up to 52 years of age and candidates for cholecystectomy because of recurrent biliary colic, the best strategy was to combine this procedure with splenectomy. Sensitivity analysis showed that the results were sensitive to the incidence of post cholecystectomy syndrome. Most remarkably an extreme sensitivity to compliance with post splenectomy infection prophylaxis was demonstrated.

Conclusions

.Our model suggested that combined prophylactic splenectomy and cholecystectomy provide a substantial gain in quality‐adjusted life expectancy for young patients and adults with mild HS and gallstones.
Postpartum onset of acute heart failure possibly due to postpartum autoimmune myocarditis. A report of three cases
Authors: Yagoro A. , Tada H. , Hidaka Y. , Ohnishi Y. , Nagata S. , Sato H. , Amino N.
Published: March 2003

Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases have transient dysfunction of affected organs. Cardiac dysfunction developed after delivery is called postpartum or peripartum cardiomyopathy. However, the aetiology of the disease is not clarified yet. Here we report three cases that developed acute heart failure in the postpartum period. One was complicated with an atrioventricular block and postpartum autoimmune thyroiditis. All patients recovered to normal cardiac function or pre‐attack condition after 1 month of therapy with conventional drugs and bed rest. All three had positive antiheart antibody detected by indirect immunofluorescence assay, and one had antibody to heart myosin detected by enzyme‐linked immunosorbent assay. Moreover, one of two patients examined revealed lymphocytic infiltration by endomyocardial biopsy. Antibodies to 26 viruses were not elevated significantly during the first 2 weeks after admission in any case. It is strongly suggested that heart failure is induced by postpartum autoimmune myocarditis, and thus clinicians should be aware of this disease.
Contributions of studies on uncoupling proteins to research on metabolic diseases
Authors: Ricquier D. , Fleury C. , Larose M. , Sanchis D. , Pecqueur C. , Raimbault S. , Gelly C. , Vacher D. , Cassard‐Doulcier A.‐M. , Lévi‐Meyrueis C. , Champigny O. , Miroux B. , Bouillaud F.
Published: March 2003

Abstract. Ricquier D, Fleury C, Larose M, Sanchis D, Pecqueur C, Raimbault S, Gelly C, Vacher D, Cassard‐Doulcier A‐M, Lévi‐Meyrueis C, Champigny O, Miroux B, Bouillaud F (Centre National de la Recherche Scientifique, Centre de Recherche sur l’Endocrinologie Moléculaire et le Développement, Meudon, France). Contributions of studies on uncoupling proteins to research on metabolic diseases. (Minisymposium: Genes & Obesity). J Intern Med 1999; 245: 637–642.

The coupling of O2 consumption to ADP phosphorylation in mitochondria is partial. This is particularly obvious in brown adipocyte mitochondria which use a regulated uncoupling mechanism generating heat production from substrate oxidation, and catalysing thermogenesis in rodents or infants in response to cold, and arousing hibernators. In the case of brown adipose tissue, the uncoupling mechanism is related to a specific protein in the inner mitochondrial membrane referred to as UCP1. Although the biological importance of UCP1 in human adults is not demonstrated, genetic analysis of various human cohorts suggested a participation of UCP1 to control of fat content and body weight. Very recently, the cloning of UCP2 and UCP3, two homologues of UCP1, has renewed the field of research on the importance of respiration control in metabolic processes and metabolic diseases. UCP2 is widely expressed in organs, whereas UCP3 is mainly present in muscles. These proteins may explain why the coupling of respiration to ADP phosphorylation is less than perfect. Their biological importance should be studied. They also represent new putative targets for drugs against metabolic diseases such as obesity.
Ethical aspects of clinical trials: the attitudes of the public and out‐patients
Authors: Madsen S. , Holm S. , Riis P.
Published: March 2003

Abstract. Madsen S, Holm S, Riis P (Copenhagen University Hospital, Herlev, and University of Copenhagen, Blegdamsvej, Denmark). Ethical aspects of clinical trials: the attitudes of the public and out‐patients. J Intern Med 1999; 245: 571–579.

Objectives.  To investigate attitudes to clinical research amongst potential research participants.

Design.  Questionnaire‐survey.

Setting.  Two medical out‐patient clinics and the background population.

Subjects.  A total of 508 randomly selected citizens in Copenhagen County (64% responded) and 200 consecutive patients attending the out‐patient clinics (64% responded).

Outcome measures. Attitudes toward different aspects of clinical research.

Results.  Positive attitudes toward medical research were disclosed. The majority found scientific testing necessary, although only a minority considered participation a moral obligation. Both personal benefits and altruistic motives for participation were highly rated, whereas former positive experiences from trial participation had only minor impact on decisions. Several respondents stated former trial participation had changed their attitudes negatively. Lack of feedback of results was of major importance for this change. Attitudes are significantly influenced by the presence of independent research ethics committees, whereas trial technicalities such as drawing lots and blinding was found problematic by only a few respondents. Altruistic motives of physicians to conduct trials were highly rated by a majority of respondents, but the motive of promoting doctors’ careers was also judged important. Respondents rated nondiscomforting procedures as acceptable or having only a small impact or strain on their lives.

Conclusion.  Attitudes toward medical research are positive amongst out‐patients and the general public. Altruistic and nonaltruistic motives both concerning trial participation and concerning the motives of physicians to conduct medical research were rated highly. Lack of feedback concerning results of trials to participants was important for a negative change in attitude toward participation.
Total homocysteine and cardiovascular disease
Authors: Nygård O. , Vollset S. E. , Refsum H. , Brattström L. , Ueland P. M.
Published: March 2003

Abstract. Nygård O, Vollset SE, Refsum H, Brattström L, Ueland PM (University of Bergen, Norway; County Hospital, Kalmar, Sweden). Total homocysteine and cardiovascular disease (Review). J Intern Med 1999; 246: 425–454.

Recent data have shown that an elevated plasma level of the amino acid homocysteine (Hcy) is a common, independent, easily modifiable and possibly causal risk factor for cardiovascular disease (CVD) which may be of equal importance to hypercholesterolemia, hypertension and smoking. This paper reviews the biochemical, clinical, epidemiological and experimental data underlying this conclusion and is critically questioning whether elevated tHcy is a causal factor.
Factors predicting lower extremity amputations in patients with type 1 or type 2 diabetes mellitus: a population‐based 7‐year follow‐up study
Authors: Hämäläinen H. , Rönnemaa T. , Halonen J.‐P. , Toikka T.
Published: March 2003

Objectives. The aim of the study was to find factors predicting lower extremity amputation in patients with type 1 or type 2 diabetes mellitus through a 7‐year follow‐up period.

Design. Follow‐up study.

Subjects. Altogether 733 diabetic patients, aged 10–79 years, were drawn from the national drug reimbursement register.

Methods. At baseline, the patients underwent a podiatric, circulatory and neurophysiological examination. Seven years later a follow‐up study was performed based on clinical and register data. Patient data for those who died during the follow‐up were collected from hospital records and death certificates. All amputations were recorded. The patients with amputation were compared with the other patients and also, in a case‐control manner, by taking three nonamputated patients matched by sex, type of diabetes, and age for each patient with amputation.

Results. The number of amputations was 25 in the sample. Compared with all patients without amputation, patients with amputation differed in altogether 24 variables concerning diabetes and its complications. Compared with the matched nonamputated patients, the amputated patients had longer duration of diabetes, lower ankle/brachial pressure index (ABI), more often history of retinopathy, nephropathy, and hypertension, more often visual handicap, elevated serum creatinine level, abnormal neurophysiological indices and electrophysiological findings. In the logistic regression analysis, vibration perception threshold, low ABI, history of retinopathy, visual handicap, and male sex were independently associated with lower extremity amputation.

Conclusions. Lower extremity amputations were strongly associated with retinopathy, nephropathy, and neuropathy. The presence of any of these complications should lead to intensified actions in order to prevent amputations. As far as arterial circulation is concerned, claudication or absent peripheral pulses were not good predictors of amputation, whereas low ABI, despite its known weaknesses, was a reliable indicator of future amputation.
Serum cholesterol is a risk factor for myocardial infarction in elderly men and women: the Rotterdam Study
Authors: Houterman S. , Verschuren W. M. M. , Hofman A. , Witteman J. C. M.
Published: March 2003

Objective. To investigate the associations of serum total and HDL cholesterol with the risk of myocardial infarction in men and women of 55 years and over.

Design. The Rotterdam Study is a population‐based prospective cohort study. In total 2453 men and 3553 women of 55 years and older were included in this study. The mean duration of follow‐up was 4 years.

Main outcome measures. Relative risks were estimated with Cox’s proportional‐hazard analysis. Cholesterol was analysed as a continuous variable and in sex‐specific quartiles.

Results. In subjects aged 55 years and older the relative risk of myocardial infarction was 1.9 in men (95% confidence interval 1.1–3.3) and 3.2 in women (1.5–6.4) in the highest compared to the lowest serum total cholesterol quartile (Q4 vs. Q1). In men and women of 70 years and older, total cholesterol remained an important risk factor for myocardial infarction (Q4 vs. Q1 relative risk 3.2; 1.3–7.7 and 2.9; 1.3–6.6, respectively). For HDL cholesterol, the relative risk in the highest compared to the lowest quartile (Q4 vs. Q1) was 0.5 in men (0.3–0.9) and 0.4 in women (0.2–0.9). HDL cholesterol was a weaker predictor in men after the age of 70 (Q4 vs. Q1 0.8; 0.3–2.1). In women of 70 years and older the relative risk was also not significant (Q4 vs. Q1 0.6; 0.3–1.3), although the trend over the quartiles was still significant.

Conclusion. Serum total cholesterol remains an important risk factor for myocardial infarction in men and women aged 70 years and older, whilst HDL cholesterol at older age remains important in women only.
A decision analysis of thrombolytic therapy compared with standard therapy in acute ischaemic stroke
Authors: Hallan S. , Åsberg A. , Indredavik B. , Widerøe T. E.
Published: March 2003

Abstract.

Hallan S, Åsberg A, Indredavik B, Widerøe TE (University Hospital of Trondheim, Trondheim, Norway). A decision analysis of thrombolytic therapy compared with standard therapy in acute ischaemic stroke. J Intern Med 1999; 246: 549–559.

Objectives. Experts draw different conclusions on whether thrombolysis can be recommended or not for acute ischaemic stroke. A major problem is weighing the improvement in functional ability against the risk of increased mortality. We wanted to examine this uncertainty regarding thrombolysis using a systematic approach and with a strong emphasis on the patient’s point of view.

Methods. We performed a decision analysis where the base case focused on an average stroke patient. We used published probabilities for different functional outcomes after standard supportive care and after adding tissue plasminogen activator (tPA), and we tried to estimate corresponding long‐term survival. We interviewed 158 subjects with the standard gamble method to elicit their preference values (utility) for these outcomes.

Results. When using the baseline data for an average stroke patient, thrombolysis with tPA was the better choice, with 48 extra quality‐adjusted living days; tPA was also superior in 117 individual decision analyses , giving from 10 to 173 extra days. However, sensitivity analysis showed that these results were highly susceptible to changes in utility for major disability, probability of early death, and long‐term survival after thrombolysis. To increase the gain as well as the margin of safety regarding the treatment choice, thrombolysis should be restricted to patients who assign low utility values < 0.6–0.7 to major poststroke disability (death = 0.0, good health = 1.0).

Conclusion. Evaluated by decision analysis, thrombolysis with tPA is on average superior to standard therapy for the few patients fulfilling the strict medical inclusion criteria. Individual incorporation of the patient’s point of view narrows the indication even further.
LPA gene: interaction between the apolipoprotein(a) size (‘kringle IV’ repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level
Authors: Røsby O. , Berg K.
Published: March 2003

Abstract. Røsby O, Berg K (University of Oslo and Ullevål University Hospital, Oslo, Norway). LPA gene: interaction between the apolipoprotein(a) size (‘kringle IV’ repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level. J Intern Med 2000: 247: 139–152.

Objectives. In order to search for factors influencing the Lp(a) lipoprotein level, we have examined the apolipoprotein(a) (apo(a)) size polymorphism as well as a pentanucleotide (TTTTA) repeat polymorphism in the 5′ control region of the LPA gene.

Design. Lp(a) lipoprotein levels were compared between individuals with different genotypes as defined by pulsed field gel electrophoresis of DNA plugs, and PCR of DNA samples followed by polyacrylamide gel electrophoresis. DNA plugs and DNA were prepared from blood samples collected from blood donors.

Results. Twenty‐seven different K IV repeat alleles were observed in the 71 women and 92 men from which apo(a) size polymorphism results were obtained. Alleles encoding 26–32 Kringle IV repeats were the most frequent. Alleles encoding seven to 11 TTTTA repeats were detected in the 84 women and 122 men included in the pentanucleotide polymorphism study, and homozygosity for eight TTTTA repeats was the most common genotype. The eight TTTTA repeat allele occurred with almost any apo(a) allele. An inverse relationship between number of K IV repeats and Lp(a) concentration was confirmed.

The contributions of the apo(a) size polymorphism and the pentanucleotide repeat polymorphism to the interindividual variance of Lp(a) lipoprotein concentrations were 9.7 and 3.5%, respectively (type IV sum of squares). Nineteen per cent of the variance in Lp(a) lipoprotein level appeared to be the result of the multiplication product (interaction) between the apo(a) size polymorphism and the pentanucleotide repeat polymorphism.

Conclusions. The contribution of the apo(a) size polymorphism alone to the variation in Lp(a) lipoprotein level was lower than previously reported. However, the multiplicative interaction effect between the K IV repeat polymorphism and the pentanucleotide repeat polymorphism may be an important factor explaining the variation in Lp(a) lipoprotein levels among the populations.
Coronary vasospasm associated with uncontrolled carcinoid tumour
Authors: Muszkat M. , Shalit M. , Lotan C. , Ben‐Yehuda A.
Published: March 2003

Abstract. Muszkat M, Shalit M, Lotan C, Ben‐Yehuda A (Hadassah University Hospital, Jerusalem, Israel). Coronary vasospasm associated with uncontrolled carcinoid tumour (Case Report). J Intern Med 2000; 247: 295–298.

We report on a 74‐year‐old carcinoid patient who, following acute myocardial infarction (MI) and percutaneous transluminal coronary angioplasty, suffered recurrent episodes of chest pain and ST‐segment elevation on ECG. This was accompanied by elevation of urinary 5‐hydroxy‐indole acetic acid. A review of the patient’s file revealed that during the 3 weeks prior to the MI, she had been treated inadvertently with a fivefold lower dosage of octreotide. Following the correction of octreotide dosage, episodes of chest pain resolved immediately. We therefore suggest that this patient suffered from recurrent coronary vasospasm due to uncontrolled carcinoid tumour.
Effects of on‐demand β2‐agonist inhalation in moderate‐to‐severe asthma. A randomized controlled trial
Authors: Richter B. , Bender R. , Berger M.
Published: March 2003

Abstract. Richter B, Bender R, Berger M (Heinrich‐Heine‐University of Duesseldorf and University of Bielefeld, Germany). Effects of on‐demand β2‐agonist inhalation in moderate‐to‐severe asthma. A randomized controlled trial. J Intern Med 2000; 247: 657–666.

Background. The appropriate use of short‐acting β2‐agonist inhalation in asthma has been the subject of controversy in recent years. Limited information is available for the group of moderate to severe asthmatics with high intake of bronchodilator inhalants and continuous anti‐inflammatory protection.

Objective. To investigate the effects of β2‐agonist reduction in marked asthma treated with multiple asthma medications.

Design. Randomized, controlled single‐blind, cross‐over trial.

Setting. Outpatient clinic at a university medical centre.

Subjects. A total of 80 adult patients with moderate‐to‐severe asthma.

Interventions. In a 1‐year study patients were assigned to on‐demand vs. regular β2‐agonist inhalation treatment.

Main outcome measures. Asthmatic episodes (primary outcome), symptoms, peak expiratory flow rates (PEF) and drug use were recorded daily. Bronchodilator and airway responsiveness, lung function indices and quality of life were assessed during five clinic visits. Also, practicability of β2‐agonist tapering in multimedicated asthmatics was analysed.

Results. More than 80% of moderate‐to‐severe asthmatics were able to reduce their β2‐agonist intake by ≥50%. Puffs per day of active therapy decreased from 7.9 in regular to 3.3 in on‐demand treated patients (P = 0.0001). The type of β2‐agonist used (salbutamol/fenoterol) had no significant impact on the study findings. Almost all parameters of control of asthma improved during the on‐demand treatment period.

Conclusion. On‐demand inhalation of short‐acting β2‐agonists in moderate‐to‐severe asthma is safe, and even in severe asthma a reduction from regular to on‐demand β2‐agonist inhalation is possible, with improved asthma control.
Ehrlichiosis associated vasculitis
Authors: Pick N. , Potasman I. , Strenger C. , Keysary A. , Schwartz I.
Published: March 2003

Abstract. Pick N, Potasman I, Strenger C, Keysary A, Schwartz I (Bnai Zion Medical Center, and Technion Faculty of Medicine, Haifa; Israel Institute for Biological Research, Ness‐Ziona, Israel; New York Medical College, USA). Ehrlichiosis associated vasculitis. J Intern Med 2000; 247: 674–678.

Objective. To test the hypothesis that some cases of primary vasculitis are caused by ehrlichiosis.

Design. A retrospective case study and serological analysis of stored sera.

Setting. University hospital.

Subjects. Fifty‐five patients discharged with any type of vasculitis over a 6‐year period.

Main outcome measures. Serology for human monocytic ehrlichiosis, and the human granulocytic ehrlichiosis agent, and polymerase chain reaction (PCR) analysis of biopsy specimens.

Results. Three patients (5.5%) had titres of 1 : 128 or higher against E. chaffeensis; none was positive for the human granulocytic ehrlichiosis agent. Skin biopsies of these patients showed lesions compatible with polyarteritis nodosa, allergic purpura and unspecified vasculitis. PCR analysis of the biopsies was unrevealing.

Conclusions. Infection with human monocytic ehrlichiosis may underlie some forms of vasculitis. If confirmed, these findings may help identify patients with vasculitis who would benefit from antibiotic treatment.
Cardiovascular risk factors and testing of relatives amongst patients with familial hyperlipidaemia one decade after a clinical trial
Authors: Tonstad S. , Hjermann I.
Published: March 2003

Abstract. Tonstad S, Hjermann I (Ullevål Hospital, Oslo, Norway). Cardiovascular risk factors and testing of relatives amongst patients with familial hyperlipidaemia one decade after a clinical trial. J Intern Med 2000; 248: 111–118.

Objectives. We examined the cardiovascular disease risk factor status of men and women with familial hyperlipidaemia (FH) 10–11 years after a clinical trial and asked whether first‐degree relatives had undergone lipid testing.

Design setting and subjects. Subjects started lipid‐lowering drugs in 1987–88. Of 60 subjects, 12 had died, one emigrated and 35 men and 12 women took part in a follow‐up clinical examination in 1998.

Results. Total cholesterol level was reduced by 41% and high‐density lipoprotein (HDL) cholesterol level increased by 13% compared with baseline (diet alone). Low‐density lipoprotein (LDL) cholesterol level was lower at the end of the trial than at follow‐up (3.6 ± 1.5 vs. 4.6 ± 2.2 mmol L–1; P = 0.01) and was higher in the group taking a low dose of a statin alone compared with other drug groups. Thus, two‐thirds of the subjects required adjustment of lipid‐lowering drugs to reach target lipid levels. One‐fifth consumed at least two food groups rich in saturated fat regularly. Body mass index (BMI) increased from 25.6 ± 2.9 to 26.8 ± 3.3 kg m–2 (P < 0.001). Five subjects compared with one at baseline had type II diabetes or glucose intolerance; 12 compared with four at baseline had a blood pressure of ≥ 160 mmHg systolic or ≥ 95 mmHg diastolic. Plasma total homocysteine was higher in subjects with coronary artery disease than in subjects without disease (11.7 ± 3.9 vs. 9.0 ± 2.3 µmol L–1; P = 0.01). Barriers to testing for lipids amongst children or siblings included family feuds, fear of increased insurance and psychiatric disease.

Conclusion. The majority of subjects were undertreated. Increases in BMI, blood pressure and glucose levels and the diet posed challenges to risk reduction. Plasma homocysteine levels should be considered in this group. Testing of all first‐degree relatives may not be achievable because of psychological barriers.
Lung function study and diffusion capacity in anorexia nervosa
Authors: Pieters T. , Boland B. , Beguin C. , Veriter C. , Stanescu D. , Frans A. , Lambert M.
Published: March 2003

Abstract.  Pieters T, Boland B, Beguin C, Veriter C, Stanescu D, Frans A, Lambert M (Cliniques, Universitaires Saint‐Luc, Brussels, Belgium). Lung function study and diffusion capacity in anorexia nervosa. J Intern Med 2000; 248: 137–142.

Study objectives. In humans, malnutrition alters the respiratory system in different ways. It impairs the ventilatory drive, decreases respiratory muscle strength and reduces immune competence. In addition, typical emphysema‐like changes were demonstrated in starved animals. The presence of emphysema has never been demonstrated in starved humans. Our objective was to investigate whether pulmonary emphysema occurs in anorexia nervosa by means of a pulmonary function study.

Population and method. We examined 24 women aged between 14 and 38 years (nine smokers). We studied the lung function including lung volumes, ventilatory capacity, maximal respiratory pressures and transfer factor, as well as PaO2.

Results. All respiratory tests were within normal limits with the exception of decreased maximal inspiratory (59% of predicted values) and expiratory pressures (35%), and increased residual volume (162%). Diffusion capacity (98.1 ± 16.2%) and transfer coefficient (98.4 ± 16.2%) were also normal. The diffusion coefficient was lower in current smokers than in those who had never smoked (P < 0.01), a difference similar to that calculated from existing reference values for transfer factor for smokers and nonsmokers.

Conclusion. In anorexia nervosa, pulmonary function tests are within normal limits with the exception of maximal pressures and residual volume. Diffusion capacity is not decreased. The present results within the limitations of the used method are not compatible with the hypothesis of starvation‐induced pulmonary emphysema.
The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: The Swedish Multimorbidity Study
Authors: Lindgärde F.
Published: March 2003

Abstract. Lindgärde F (Department of Vascular Disease, Malmö University Hospital, University of Lund, Malmö, Sweden). The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: The Swedish Multimorbidity Study. J Intern Med 2000; 248: 245–254.

Objective. To assess the effect of orlistat on body weight and cardiovascular risk amongst obese patients at high coronary risk.

Design. After screening, patients entered a two‐week single‐blind placebo lead‐in period, during which they followed a mildly hypocaloric diet, before being randomized to double‐blind treatment with either orlistat 120 mg or placebo three times daily, in conjunction with dietary intervention for 1 years.

Setting. The study was conducted at 33 primary care centres in Sweden.

Subjects. A total of 382 obese adults (body mass index 28–38 kg m–2) with type 2 diabetes, hypercholesterolaemia and/or hypertension were recruited, of whom 376 were randomized to orlistat (n = 190) or placebo (n = 186).

Main outcome measures. Change in body weight, waist and hip circumferences, blood pressure, serum lipid profile, fasting glucose and HbA1c.

Results. After 1 years, mean weight loss was significantly greater with orlistat compared with placebo (5.9% vs. 4.6%; P < 0.05). Moreover, significantly more orlistat‐treated patients than placebo recipients maintained weight loss of ≥ 5% (54.2% vs. 40.9%; P < 0.001). Orlistat was also associated with significantly greater improvements than placebo in total serum cholesterol (– 3.3% vs. –0.5%; P < 0.05), LDL‐cholesterol (– 7.0% vs. –1.1%; P < 0.05), fasting glucose (5.1% vs. –0.1%; P < 0.01) and HbA1c (– 2.7% vs. –0.5%; P < 0.05). Similar results were reported for the subgroup of patients with type 2 diabetes. Orlistat was well tolerated.

Conclusions. Treatment with orlistat in conjunction with diet promotes significantly greater weight loss and cardiovascular risk factor reduction than diet alone amongst obese patients at high risk of future coronary events.
Hepatitis C in clinical practice
Authors: Larson A. M. , Carithers R. L.
Published: March 2003

Abstract. Larson AM, Carithers RL (University of Washington, Seattle, WA, USA). Hepatitis C in clinical practice (Review). J Intern Med 2001; 249: 111–120.

Hepatitis C virus infection is now one of the most important causes of chronic liver disease. Primary care physicians play an important role in the diagnosis and initial work‐up of patients infected with this virus. Understanding which patients may be at risk is the first step. By understanding the correct use of hepatitis C virus diagnostic testing and the risk and benefits of antiviral therapy, providers will be better equipped to screen and counsel their patients.
Plasma fibrinogen level and long‐term prognosis in Norwegian middle‐aged patients with previous myocardial infarction. A 10 year follow‐up study
Authors: Retterstol L. , Kierulf P. , Pedersen J. C. , Bohn M. , Bakken A. , Erikssen J. , Berg K.
Published: March 2003

Abstract. Retterstol L, Kierulf P, Pedersen JC, Bohn M, Bakken A, Erikssen J, Berg K (Institute of Medical Genetics, University of Oslo and Ullevål University Hospital, Oslo; and Central Hospital of Akershus, Nordbyhagen, Norway). Plasma fibrinogen level and long‐term prognosis in Norwegian middle‐aged patients with previous myocardial infarction. A 10 years follow‐up study. J Intern Med 2001; 249: 511–518.

Objectives. To investigate the prognostic value of plasma fibrinogen level amongst middle‐aged survivors of myocardial infarction (MI).

Design. Prospective cohort study.

Settings. Determination of fibrinogen and other prognostic variables in MI patients recruited in a presumably stable phase of coronary heart disease (CHD).

Subjects. A total of 247 middle‐aged CHD patients (54 women and 193 men) who had their first MI at age ≤60 (women) or ≤55 (men) were recruited at least 3 months after (mean 2.1 years) the most recent MI.

Main outcome measures. The primary endpoint was total mortality, and the secondary endpoint was cardiac deaths. The tertiary endpoint was major cardiac events (cardiac death, MI and cardiac arrest).

Results. During a follow‐up period of 10 years a total of 44 patients had died, 36 from cardiac causes. Major cardiac event occurred in 70 patients. After adjusting for age, ejection fraction (EF), total serum cholesterol (TC), smoking and hypertension, patients in the top quartile of fibrinogen (≥4.0 g L–1) had a relative risk (RR) of 1.8 (95% CI 1.0–3.6) (P=0.07) for death of all causes. The top quartile of fibrinogen was a stronger predictor of cardiac death; RR=2.2 (95% CI 1.1–4.4) (P=0.03), whilst the effect on the endpoint major cardiac event was not significant; RR=1.1 (95% CI 0.6–1.9) (P=0.69).

Conclusions. A plasma fibrinogen level in the top quartile predicted cardiac death in middle‐aged patients who had suffered MI.
Transforming growth factor (TGF)‐β1 inversely related to vascular cell adhesion molecule‐1 in postmenopausal women with coronary artery disease. A possible mechanism for the putative cardioprotective role of TGF‐β1?
Authors: Os I. , Djurovic S. , Seljeflot I. , Berg K.
Published: March 2003

Abstract. Os I, Djurovic S, Seljeflot I, Berg K (Ullevål University Hospital, Oslo, Norway). Transforming growth factor (TGF)‐β1 inversely related to vascular cell adhesion molecule‐1 in postmenopausal women with coronary artery disease. A possible mechanism for the putative cardioprotective role of TGF‐β1? J Intern Med 2002; 251: 223–227.

Objective and design. Transforming growth factor beta (TGF‐β1) is involved in a variety of physiological processes as well as in many diseases. Both in vitro and in vivo evidence suggest that TGF‐β1 may influence atherogenesis and a dominant protective role of TGF‐β1 on coronary arteries has been proposed. On the other hand, increased levels of soluble adhesion molecules have been found in patients with atherosclerosis, and adhesion of monocytes to the endothelium followed by migration to the intima, has been proved to be an early event in atherosclerosis. The purpose of the present investigation was to look at a possible relationship between circulating active TGF‐β1 and adhesion molecules in postmenopausal women with angiographically verified coronary heart disease (CHD) (n=118).

Results. Serum levels of the active form of TGF‐β1 showed a tendency to be lower in patients with increasing number of vessels with more than 50% stenosis (P=0.058), and there was higher TGF‐β1 in the group with one vessel disease compared with those with two or more vessels affected (P=0.041). Additionally, negative association between TGF‐β1 and VCAM‐1 was found (r=–0.26, P=0.023). However, no associations were observed between TGF‐β1 and intercellular adhesion molecule‐1 (ICAM‐1) or E‐selectin in the present study.

Conclusion. We observed an inverse correlation between the active form of TGF‐β1 and VCAM‐1 in postmenopausal women with verified CHD. These results may suggest a role of TGF‐β1 in CHD.
Protein tyrosine phosphatase 1B: a new target for the treatment of obesity and associated co‐morbidities
Authors: Ukkola O. , Santaniemi M.
Published: March 2003

Abstract. Ukkola O, Santaniemi M (University of Oulu, Oulu, Finland). Protein tyrosine phosphatase 1B: a new target for the treatment of obesity and associated co‐morbidities (Review). J Intern Med 2002; 251: 467–475.

Impaired insulin action is important in the pathophysiology of multiple metabolic abnormalities such as obesity and type 2 diabetes. Protein tyrosine phosphatase 1B (PTP1B) is considered a negative regulator of insulin signalling. This is best evidenced by studies on knockout mice showing that lack of PTP1B is associated with increased insulin sensitivity as well as resistance to obesity and in vitro studies whilst studies in animals and humans have given contradictory results. However, several studies support the notion that insulin signalling can be enhanced by the inhibition of PTP1B providing an attractive target for therapy against type 2 diabetes and obesity. In addition, recent genetic studies support the association between PTP1B with insulin resistance. The development of PTP1B inhibitors has already begun although it has become clear that is not easy to find both a selective, safe and effective PTP1B inhibitor. The objective of this paper is to review the current evidence of PTP1B in the pathophysiology of obesity, type 2 diabetes and cancer as well as in the treatment of these disorders.
The effects of exercise training on walking function and perception of health status in elderly patients with peripheral arterial occlusive disease
Authors: Tsai J. C. , Chan P. , Wang C. H. , Jeng C. , Hsieh M. H. , Kao P. F. , Chen Y. J. , Liu J. C.
Published: March 2003

Abstract. Tsai JC, Chan P, Wang CH, Jeng C, Hsieh MH, Kao PF, Chen YJ, Liu JC (Taipei Medical University‐Wan Fang Hospital, Taipei, Taiwan). The effects of exercise training on walking function and perception of health status in elderly patients with peripheral arterial occlusive disease. J Intern Med 2002; 252: 448–455.

Objective. To determine the effects of 12‐week exercise programme on ambulatory function, free‐living daily physical activity and health‐related quality of life in disabled older patients with intermittent claudication.

Design. Prospective, randomized controlled trial.

Setting. University Medical Center and Veterans Affairs Medical Center, Taipei, Taiwan.

Subjects. Thirty‐two of 64 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise training and 32 to usual care control. Five patients from the exercise group and six patients from the control group dropped out, leaving 27 and 26 patients, respectively, completing the study in each group.

Interventions. Twelve weeks of treadmill exercise training.

Main outcome measures. Treadmill walking time to onset of claudication pain and to maximal claudication pain, 6‐min walk distance, self‐reported ambulatory ability and perceived health‐related quality of life (QOL).

Results. Compliance of exercise programme was 83% of the possible sessions. Exercise training increased treadmill walking time to onset of claudication pain by 88% (P < 0.001), time to maximal pain by 70% (P < 0.001), and 6‐min walk distance by 21% (P < 0.001).

Subjects. Perception of health‐related QOL improved from 12% to 178% in the exercise group. These improvements were significantly better than the changes in the control group (P < 0.05).

Conclusions. Significant improvements in claudication following 12‐week exercise training in elderly PAOD patients were observed. Increase in treadmill walking time to maximal claudication pain in these patients translated into the improvement of perceived physical health, which enabled the patients to become more functionally independent.
Hyperinsulinaemia as long‐term predictor of death and ischaemic heart disease in nondiabetic men: The Malmö Preventive Project
Authors: Nilsson P. , Nilsson J‐Å. , Hedblad B. , Eriksson K‐F. , Berglund G.
Published: March 2003

Abstract. Nilsson P, Nilsson J‐Å, Hedblad B, Eriksson K‐F, Berglund G. (University Hospital, Malmö, Sweden) Hyperinsulinaemia as long‐term predictor of death and ischaemic heart disease in nondiabetic men: The Malmö Preventive Project.J Intern Med2003;253:136–145.

Objectives. Prospective studies have indicated that hyperinsulinaemia/insulin resistance is a risk factor for ischaemic heart disease (IHD), the risk decreasing with time of follow‐up. Few studies have so far investigated the role of hyperinsulinaemia in the prediction of long‐term total mortality.

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

Subjects. A total of 6074 nondiabetic, middle‐aged, healthy Swedish males.

Screening examination. We determined IHD risk factors including blood glucose and plasma insulin before and 2 h after an oral glucose tolerance test (OGTT). Total follow‐up time was 19 years. Hyperinsulinaemia was defined as values above the 10th decentile of fasting or 2 h insulin concentration.

Main outcome measures. Total mortality and cardiac event (CE) rate for IHD.

Results. Unadjusted relative risks (RRs) for both death and CE were J‐shaped with the highest relative risk (RR: 1.4–1.6) in the hyperinsulinaemic group compared with all other men. The RRs for death and CE were significant for fasting insulin but became nonsignificant after adjustment for other risk factors and also with a longer follow‐up. The risk of death in hyperinsulinaemic men, defined on the basis of 2‐h insulin level, increased with time of follow‐up and was still significantly increased after 19 years [RR: 1.32 (95% CI: 1.05–1.65], even after adjustment for other risk factors.

Conclusions. Fasting hyperinsulinaemia was a predictor of total mortality and IHD in nondiabetic men, although not more significantly after adjustment for other risk factors and with lengthening of follow‐up time. The 2‐h postglucose hyperinsulinaemia appeared to be a stronger and independent predictor of mortality over long‐term follow‐up. These findings support the view that insulin resistance with associated cluster of risk factors predicts increased long‐term risk of mortality and IHD.
No acute impact of haemodialysis treatment on free radical scavenging enzyme gene expression in white blood cells
Authors: Schettler V. , Kühn W. , Kleinoeder T. , Armstrong V. W. , Oellerich M. , Müller G. A. , Wieland E.
Published: March 2003

Abstract.  Schettler V, Kühn W, Kleinoeder T, Armstrong VW, Oellerich M, Müller GA, Wieland E (Georg‐August‐University, Göttingen, Germany). No acute impact of haemodialysis treatment on free radical scavenging enzyme gene expression in white blood cells. J Intern Med 2003; 253: 201–207.

Objective.  Oxidative stress has been implicated in the side‐effects caused by haemodialysis (HD) treatment.

Design.  In the present study we have investigated whether gene expression of the enzymatic defence system provided by cellular glutathione peroxidase (GPx‐1), phospholipid glutathione peroxidase (GPx‐4), glutathione reductase (GSSG‐R), glutathione synthethase (GSH‐S), Cu/Zn‐superoxide dismutase (SOD‐1) and catalase (CAT) is affected by HD.

The GPx‐1, GPx‐4, GSSG‐R, GSH‐S, SOD‐1 and CAT mRNA were determined in white blood cells by quantitative reverse transcriptase‐polymerase chain reaction with the LightCycler® instrument and transcription elongation factor‐2 as reference gene at the start (SD) and immediately after (ED) dialysis treatment (n = 36). In a subgroup (n = 10), messenger RNA (mRNA) expression was determined hourly during a 5 h HD.

Results.  The expression of GPx‐1, GPx‐4, GSSG‐R, GSH‐S, SOD‐1 and CAT mRNA was not affected by a single HD treatment. All mRNAs were significantly (P < 0.05) increased in HD patients [median (16. percentiles (perc.); 84. perc.)]: GPx‐1: 2.18 (0.89; 3.23); GPx‐4: 0.41 (0.26; 0.74); GSSG‐R: 0.04 (0.02; 0.10); GSH‐S: 0.04 (0.02; 0.08); SOD‐1: 0.32 (0.20; 0.62); CAT: 0.12 (0.06; 0.18) when compared with healthy blood donors (GPx‐1: 0.91 (0.60; 1.44); GPx‐4: 0.27 (0.16; 0.43); GSSG‐R: 0.02 (0.01; 0.02); GSH‐S: 0.02 (0.02; 0.04); SOD‐1: 0.15 (0.10; 0.18); CAT: 0.07 (0.04; 0.16).

Conclusions.  These results show that the HD procedure does not acutely affect the antioxidant defence system on the gene level but suggest that the chronic stress caused by uraemia and/or HD may cause gene induction of the enzymatic defence system.
Characterization of 25–75 nm phases found at the periphery of multiphase inclusions: techniques comparison and selection
Authors: Blais  , L'Espérance  , Baril
Published: March 2003

It is believed that particular phases found at the surface of inclusions in steel welds favour the formation of acicular ferrite. Such a microstructure increases tremendously the toughness of the weld deposits. Until now, it is not clear which phases are favourable, the uncertainty being partly due to the difficulty of characterizing phases with sizes of about 100 nm at the periphery of inclusions. We compared characterization techniques including scanning electron microscopy, transmission electron microscopy, energy‐dispersive spectrometry and parallel electron energy‐loss spectroscopy. We found that, in general, it is possible to identify the phases unambiguously by comparing the results of energy‐dispersive spectrometry and electron diffraction patterns in the transmission electron microscope on samples prepared by carbon extraction replicas. For cases where the size is very small (< 50 nm) and/or when similarities in composition and crystal structure are difficult to differentiate, spectrum imaging using parallel electron energy‐loss spectroscopy on samples prepared by ultramicrotomy is the most powerful characterization technique.
The efficiency of X‐ray production at low energies
Authors: Joy
Published: March 2003

The absolute efficiency of X‐ray production has been determined for the K‐lines of Al, Si and Cu; for the L‐lines of Fe, Co, Cu, Ge and As; and for the M‐lines of Hf, Ir, Pt, Au and Bi, using overvoltage ratios in the range 1–10. These emissions, with the exception of the Cu K, have critical excitation energies below 2.6 keV and are therefore typical of the lines used for X‐ray microanalysis at low beam energies. For K‐lines it is found that the experimental results are in good agreement with a Bethe, or a Casnati, cross‐section model. For the L‐ and M‐lines a Monte Carlo technique has been used to find an effective X‐ray generation cross‐section for each of the elements. The functional forms of these cross‐sections are found to be in general agreement with proposed theoretical models.
Estimation of average particle size from vertical projections
Authors: Gokhale A. M. , BeneŠ V.
Published: March 2003

A new stereological relationship is derived for the estimation of average size (average width) of a collection of convex particles in a 3D microstructure. The average size is estimated from measurements performed on projected images of the microstructure generated by total vertical projections. The stereological relationship is as follows: D=ĪC/(2N0β). D is the average width, ¯IC is the average absolute number of intersections between the specifically oriented and regularly spaced cycloid shape test lines and particle boundaries observed in the total vertical projections, N0 is the total number of particles observed in the total vertical projection and the parameter β is a characteristic of the measurement grid; it has units of reciprocal of length. The result is applicable to any arbitrary collection of convex particles; the particle orientations need not be isotropic. Only ‘intersection counts’ are required; it is not necessary to measure sizes of the particles in the projected images.