bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow‐up cohort of the Heart Disease and Diabetes Risk Indicators in a Screened Cohort study (HDDRISC‐1)
Authors: Godsland  , Leyva  , Walton  , Worthington  , Stevenson
Published: March 2003

Godsland IF, Levya F, Walton C, Worthington M, Stevenson JC (Imperial College School of Medicine, London, UK). Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow‐up cohort of the Heart Disease and Diabetes Risk Indicators in a Screened Cohort study. J Intern Med 1998; 244: 33–41.

Objectives

To investigate the associations between risk factors for cardiovascular disease and cigarette smoking, alcohol intake, and physical activity in a group of predominantly healthy men.

Design

Cohort study with baseline characterisation, clinical follow‐up, and identification of predictors of coronary artery disease and diabetes.

Setting

University hospital metabolic day ward.

Subjects

Participants in a company health programme (n= 742).

Main outcome measures

Routine haematology and biochemistry, cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol (on a subset of 522 subjects), and glucose and insulin levels during a 3 h oral glucose tolerance test (OGTT).

Results

Independent associations with previous cigarette smoking included high uric acid and low HDL cholesterol, and with current cigarette smoking, high haemoglobin and white cell count and low OGTT insulin. Increasing alcohol intake was associated with increasing blood pressure, uric acid, HDL cholesterol and fasting glucose. The moderate range of exercise intensity in this cohort was associated with decreasing systolic blood pressure, fasting insulin and OGTT glucose and insulin. Factor analysis distinguished principal factors comprising features of the metabolic syndrome with low physical activity, and high white cell count, high haemoglobin concentration and low HDL cholesterol with increasing previous and current cigarette smoking and alcohol intake.

Conclusions

Some characteristics of the metabolic syndrome were seen with previous but not current smoking habit. Regular alcohol consumption was associated with mainly unfavourable metabolic characteristics, although there was an independent beneficial association with HDL cholesterol. The improved metabolic syndrome profile seen with increasing exercise is consistent with even moderate degrees of physical activity having beneficial effects on metabolism.
Recurrent hypoglycaemia in multiple myeloma: a case of Munchausen syndrome by proxy in an elderly patient
Authors: Ben‐Chetrit  , Melmed
Published: March 2003

Ben‐Chetrit E, Melmed RN (Hadassah University Hospital, Jerusalem, Israel). Recurrent hypoglycaemia in multiple myeloma: a case of Munchausen syndrome by proxy in an elderly patient (Case Report). J Intern Med 1998; 244: 175–8.

A 73‐year‐old woman with multiple myeloma experienced four episodes of loss of consciousness, convulsions and profuse sweating whilst she was in the hospital. A thorough investigation in the department of medicine disclosed that with each attack, she had a serum glucose <1.6 mm L−1, insulin level >1400 pMol L−1 (N – <150) and a normal level of serum C‐peptide. Since she had no anti‐insulin antibodies (which may rarely exist in multiple myeloma), a diagnosis of exogenous injection of insulin was made. A search for a possible perpetrator discovered that the patient had a daughter who was a surgical nurse and who was genuinely concerned whenever she was told that her mother was about to be discharged from the hospital. If she was the perpetrator in the present case, then it is possible that the motive for such an action was to postpone the mother's discharge from hospital. This case is an example of a ‘factitious disease by proxy’ in an elderly patient. The aim of the present report is to alert the medical personnel to the possibility that Munchausen's syndrome by proxy may also occur in the elderly.
Delayed chylomicron remnant clearance in subjects with heterozygous familial hypercholesterolaemia
Authors: Castro Cabezas M. , DE Bruin T. W. A. , Westerveld H. E. , Meijer E. , Erkelens D. W.
Published: March 2003

Castro Cabezas M, De Bruin TWA, Westerveld HE, Meijer E, Erkelens DW (Departments of Internal Medicine and Endocrinology, University Hospital Utrecht and University Hospital Maastricht, The Netherlands). Delayed chylomicron remnant clearance in subjects with heterozygous familial hypercholesterolaemia. J Intern Med 1998; 244: 299–307.

Objectives

To study the role of the LDL receptor in the clearance of chylomicron remnants in humans.

Design

Chylomicron remnant clearance was studied in five untreated subjects with heterozygous familial hypercholesterolaemia (FH) and nine normolipidaemic controls, by oral retinyl palmitate‐fat loading tests. Fasting plasma triglycerides (TG), which are important determinators of chylomicron and remnant clearance, were not significantly different between FH (1.76 ± 0.32 mmol L−1, mean ± SEM) and controls (1.26 ± 0.18 mmol L−1). Chylomicrons (Sf > 1000) and their remnants (Sf < 1000) were separated by flotation and their clearance was estimated by calculating the area under the 24 h‐retinyl palmitate curve (AUC‐RP). The factors determining chylomicron and remnant clearance were studied by univariate and multiple regression analysis.

Results

Triglyceride clearance in plasma, Sf > 1000 fractions and Sf < 1000 fractions was not significantly different between FH subjects and controls. In subjects with heterozygous FH, chylomicron remnant clearance was two‐fold delayed (AUC‐RP, 49.39 ± 11.61 h.mg L−1) compared to controls (27.45 ± 3.95 h.mg L−1; P= 0.048). Moreover, 28.4% higher fasting plasma TG in FH resulted in 44.4% higher areas under the remnant‐curves compared to controls. The clearance of chylomicron RP was associated to plasma apo E (β= 0.73, P= 0.011), plasma LDL cholesterol (β= 0.62, P= 0.018) and plasma TG (β= 0.58, P= 0.029). The clearance of remnant RP was associated to the diagnosis (FH vs. non‐FH), but not to the well‐known determinants of remnant clearance like plasma TG.

Conclusions

The clearance of chylomicrons and large remnants isolated in the Sf > fraction depends primarily on the apo B, E (LDL) receptor and to a lesser extent on plasma triglycerides. The clearance of smaller chylomicron remnants isolated in the Sf < 1000 depends to a large extent on the apo B, E (LDL) receptor.
Intestinal endocrine cells in myotonic dystrophy: an immunocytochemical and computed image analytical study
Authors: Rönnblom A. , Danielsson Å. , El‐Salhy M.
Published: March 2003

Objectives.To study intestinal endocrine cell types in patients suffering from myotonic dystrophy (MD) and diarrhoea.

Design.Comparative study between MD patients and matched controls.

Setting.Departments of Medicine, Central Hospital, Boden, and University Hospital, Umeå, Sweden.

Subjects.Ten patients with MD (four males and six females) and suffering from diarrhoea. Ten healthy volunteers served as controls for the duodenal study and 13 patients under investigation for rectal bleeding and with endoscopically normal mucosa were controls for the rectal study.

Measurements.The duodenal and rectal endocrine cell types were identified by immunohistochemical investigation and quantified by computed image analysis.

Results.The total endocrine cell area in the duodenum as demonstrated by chromogranin A‐immunoreactivity was significantly increased in MD as compared with the controls (126 ± 58 vs. 48 ± 22 × 103 µm2 mm−2in crypts and 230 ± 183 vs. 28 ± 22 in villi, respectively,P < 0.01). The increase included all types of endocrine cells studied, namely those positive for serotonin, cholecystokinin (CCK)/gastrin, secretin, gastric inhibitory peptide (GIP) and somatostatin. In the rectum, the total endocrine cell area as determined by chromogranin A‐immunoreactivity was also significantly increased, but there was no statistical difference between the controls and patients with respect to the area of serotonin‐, peptide YY (PYY)‐, pancreatic polypeptide (PP)‐ or somatostatin‐immunoreactive cells.

Conclusions.The increase in endocrine cell area indicates a disturbed endocrine regulation of the gastrointestinal tract that may contribute to the development of gastrointestinal symptoms encountered in MD patients.
QT dispersion and late potentials during doxorubicin therapy for non‐Hodgkin’s lymphoma
Authors: Nousiainen T. , Vanninen E. , Rantala A. , Jantunen E. , Hartikainen J.
Published: March 2003

Objectives. To investigate effects of doxorubicin therapy on cardiac electrophysiology, with special emphasis on QT dispersion and late potentials, in lymphoma patients.

Design. Prospective study.

Setting. University hospital.

Subjects. Twenty‐eight adult non‐Hodgkin’s lymphoma patients who received doxorubicin to a cumulative dose of 400–500 mg m–2.

Main outcome measures. Standard 12‐lead electrocardiogram (ECG) and signal‐averaged ECG (SAECG) recordings were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m–2.

Results. Heart rate‐corrected QT interval (QTc) increased from 402 ± 4 to 416 ± 5 ms (P = 0.002) during the study period. QT dispersion (variability in QT interval duration amongst the different leads of the standard 12‐lead ECG) increased from 24.1 ± 2.5 to 35.0 ± 2.8 ms (P = 0.041) and QTc dispersion increased from 26.5 ± 2.5 to 39.0 ± 3.5 ms (P = 0.039). Five patients (18%) developed QT dispersion exceeding 50 ms. In addition, two patients (7%) developed late potentials during doxorubicin therapy. The changes in QTc duration, QT dispersion and late potentials occurred independently of the impairment of left ventricular function.

Conclusions. Prolongation of QTc, increased QT dispersion and development of late potentials are indicative of doxorubicin‐induced abnormal ventricular depolarization and repolarization. QT dispersion and late potentials are both known to be associated with increased risk of serious ventricular dysrhythmias and sudden death in various cardiac diseases. Thus, follow‐up of these parameters might also be useful in assessing the risk of late cardiovascular events in cancer patients treated with anthracyclines.
Serum urate determines antioxidant capacity in middle‐aged men – a controlled, randomized diet and exercise intervention study
Authors: Rosell M. , Regnström J. , Kallner A. , Hellénius M.‐L.
Published: March 2003

Rosell M, Regnström J, Kallner A, Hellénius M‐L (Karolinska Hospital and Karolinska Institute, Stockholm, Sweden). Serum urate determines antioxidant capacity in middle‐aged men – a controlled, randomized diet and exercise intervention study. J Intern Med 1999; 246: 219–226.

Objectives. To study whether advice on diet and/or exercise, given in order to reduce cardiovascular risk factors in middle‐aged men, affects the intake of antioxidants, urate concentration and the total antioxidant capacity in serum.

Design. A 6‐month randomized controlled intervention study.

Setting. Primary Health Care in Sollentuna, Stockholm, and the Department of Medicine, Karolinska Hospital, Stockholm, Sweden.

Subjects. One hundred and fifty‐eight healthy men (46.2 ± 5.0 years) with moderately raised cardiovascular risk factors.

Interventions. Advice on diet (D, n = 40), exercise (E, n = 39), diet and exercise (DE, n = 39) and a control group (C, n = 39).

Main outcome measures. Dietary intake, exercise habits, S‐urate and the antioxidant capacity in serum (TAOC).

Results. After 6 months, changes in dietary and exercise habits were seen in all three intervention groups and favourable effects were seen on BMI, waist circumference, blood pressure, S‐cholesterol and fasting insulin. The intake of α‐tocopherol was decreased in groups D and E (P < 0.01) and β‐carotene was increased in groups D and DE (P < 0.01). In group DE, the intake of vitamin C was increased (P < 0.05). S‐urate was reduced in group D from 345 to 325 µmol L–1 (P < 0.05). No significant changes in TAOC were seen in any group. S‐urate and TAOC were correlated (r = 0.58, P < 0.001) and S‐urate was correlated to several parameters in the metabolic syndrome.

Conclusion. Favourable changes in diet and exercise reduced several cardiovascular risk factors but did not affect the total antioxidant capacity in serum. S‐urate was a strong determinant of the antioxidant capacity.
Quality of self‐care in patients on replacement therapy with hydrocortisone
Authors: Flemming T. G. , Kristensen L. Østergaard
Published: March 2003

Abstract. Flemming TG, Østergaard Kristensen L (Herlev University Hospital, Herlev, Denmark). Quality of self‐care in patients on replacement therapy with hydrocortisone. J Intern Med 1999; 246: 497–501.

Objectives. To assess the quality of self‐care in patients receiving replacement therapy with hydrocortisone for primary or secondary adrenal insufficiency.

Design. A questionnaire‐based survey.

Setting. The outpatient Clinic of Endocrinology at the University Hospital in Herlev, Denmark.

Subjects. Ninety‐seven patients identified from the case reports of the clinic. All patients had received repeated oral information about hydrocortisone treatment and dose adjustments. Eighty‐four (87%) patients completed the questionnaire.

Main outcome measures. Ability to act appropriately in case of physical stress, possession of a ‘Steroid warning card’, number and nature of episodes of physical stress during the past year and self‐experienced level of information was recorded.

Results. Thirty‐nine (46%) of the patients were not sufficiently skilled in coping with physical stress. This was more prominent in the elderly patients. Seventeen (20%) did not possess a ‘steroid warning card’. Thirty‐seven (44%) had experienced at least one febrile episode and 24 (29%) had been admitted to hospital during the past year. Fifty (60%) felt themselves to be well informed, but this did not correlate with the ability to act appropriately.

Conclusions. The study shows the need for continuous education of patients with adrenal insufficiency. Oral instructions should be supplemented with written information or a more detailed and structured education.
Factors associated with the use of various medications amongst patients with severe coronary artery disease
Authors: Herlitz J. , Brorsson B. , Werkö L. ,   for the SECOR/SBU* Project Group
Published: March 2003

Aim. To describe variations by age, sex, symptom severity and hospital region in the use of various medications amongst patients with stable angina pectoris who are candidates for coronary revascularization.

Patients. Patients (n = 2030) with chronic stable angina pectoris participating in a national survey evaluating the appropriateness of the use of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG).

Methods. As part of a national study of the appropriateness of coronary revascularization, data were prospectively collected on patients referred for consideration of coronary revascularization to seven of the eight public Swedish heart centres that performed approximately 92% of all bypass operations in Sweden in 1994.

Results. Amongst all patients 76% were treated with beta blockers, 41% with calcium antagonists and 71% with long‐acting nitrates and 70% were treated with at least two of these three drugs. Eighty‐two per cent of the patients used aspirin and 14% lipid‐lowering drugs. According to logistic regression analysis, with medication as the dependent variable and independent variables of age, sex, angina functional class, findings at exercise test, history of various diseases and region in Sweden where the investigation took place, the most consistent factor explaining the use of various medications was found to be geographical region. A previous history of acute myocardial infarction (AMI) was also associated with the use of all drugs and age was associated with all with the exception of beta blockers. Sex was not an independent factor explaining the use of any of the drugs.

Conclusion. In a national survey including patients with stable angina pectoris who are potential candidates for coronary revascularization, the most important predictor for the use of various medications was the geographical region in which the investigation took place.
Epidemics of vascular toxicity and pulmonary hypertension: what can be learned?
Authors: Egermayer P.
Published: March 2003

Abstract. Egermayer P (Canterbury Respiratory Research Group, Christchurch, New Zealand). Epidemics of vascular toxicity and pulmonary hypertension: what can be learned? (Review). J Intern Med 2000; 247: 11–17.

Epidemics of vascular disease caused by toxins and infectious agents affecting both humans and animals have been common in history. Examples of agents implicated include anorexients, ergotamine, mercury, arsenic, vinyl chloride, thorotrast, plant alkaloids, nitrites, toxic oil, tryptophan and bacterial, viral and parasitic infections. A major characteristic of these disorders is endothelial dysfunction, which may manifest itself in vasospastic disorders, sclerodermiform skin lesions, fibrosis, osteolytic lesions, polyneuropathy and portal and pulmonary hypertension. Angiosarcoma may also be a late outcome. These diseases are more common than is generally appreciated. The aetiology is usually multifactorial. This and other factors contribute to delayed recognition.
The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine
Authors: Hvas A. M. , Juul S. , Gerdes L. U. , Nexø E.
Published: March 2003

Abstract. Hvas AM, Juul S, Gerdes LU, Nexø E (Aarhus University and Aarhus University Hospital, Aarhus, Denmark). The marker of cobalamin deficiency, plasma methylmalonic acid, correlates to plasma creatinine. J Intern Med 2000; 247: 507–512.

Objective. To examine the relationship between the two diagnostic tests, plasma methylmalonic acid and plasma cobalamins, and their association with plasma creatinine, age and sex.

Design. Cross‐sectional study of simultaneous laboratory measurements.

Setting. County of Aarhus, Denmark.

Subjects. Records on 1689 patients who had their first plasma methylmalonic acid measurement during 1995 and 1996, and who had a simultaneous measurement of plasma cobalamins . Plasma creatinine values measured within a week of measurements of plasma methylmalonic acid and plasma cobalamins were available for 1255 of the patients.

Main outcome measures. Predictors of variation in plasma methylmalonic acid; plasma cobalamins, plasma creatinine, age and sex.

Results. Plasma methylmalonic acid was positively correlated with plasma creatinine, even for plasma creatinine within the normal range. These associations remained in a multiple regression analysis. For plasma cobalamins below 200 pmol L–1, there was a strong negative correlation between plasma methylmalonic acid and plasma cobalamins, whilst the association was weak for higher plasma cobalamin levels. Plasma methylmalonic acid increased and plasma cobalamins decreased with age.

Conclusions. The strong correlation between plasma methylmalonic acid and plasma creatinine suggests that plasma creatinine – also within the normal range – must be taken into consideration when interpreting plasma methylmalonic acid.
Attack rate, mortality and case fatality for acute myocardial infarction in Sweden during 1987–95. Results from the National AMI Register in Sweden
Authors: Rosén M. , Alfredsson L. , Hammar N. , Kahan T. , Spetz C.‐L. , Ysberg A.‐S.
Published: March 2003

Abstract. Rosén M, Alfredsson L, Hammar N, Kahan T, Spetz C‐L, Ysberg A‐S (Centre for Epidemiology, National Board of Health and Welfare, Stockholm; University of Umeå, Umeå; Karolinska Institutet, Stockholm; Karolinska Hospital, Stockholm; and Karolinska Institutet, Danderyd Hospital, Danderyd, Sweden). Attack rate, mortality and case fatality for acute myocardial infarction in Sweden 1987–95. Results from the National AMI Register in Sweden. J Intern Med 2000; 248: 159–164.

Objective. To assess trends in attack rate, mortality and case‐fatality of acute myocardial infarction (AMI) in Sweden.

Setting. All 303 324 Swedes discharged from hospitals, or deceased, with a diagnosis of AMI between 1987 and 1995.

Design. Analysis based on the National AMI Register in Sweden. The National AMI Register was assembled by linking the records of the National Hospital Discharge Register and the National Cause of Death Register in Sweden.

Main outcome measures. Age‐standardized attack rate, mortality and case fatality rates for AMI.

Results. Between 1987 and 1995, the age‐standardized attack rate of AMI declined by 11% for men and 10% for women, whilst mortality from AMI decreased by 14% for both sexes. The decrease was most pronounced for men below the age of 64, with a reduction of 22% in attack rate and nearly 30% in mortality. There was no change over time in the case fatality rates on the date of attack, including also deaths outside hospital, whilst case fatality within 28 days decreased from 49 to 45% amongst men, and 45 to 42% amongst women. This reduction persisted over 1 year of follow‐up.

Conclusions. The decrease in attack rate of AMI in Sweden may be attributed both to changes in risk factors amongst the population and to improved medical intervention. The decline in case fatality rates indicates that improved treatment of patients with AMI has contributed to the reduction in mortality. However, the high, and essentially unchanged, proportion of deaths outside hospital stresses the importance of disease prevention.
Telemedicine: barriers and opportunities in the 21st century
Authors: Stanberry B.
Published: March 2003

Abstract. Stanberry B (Centre for Law Ethics and Risk in Telemedicine, Cardiff, Wales, UK). Telemedicine: barriers and opportunities in the 21st century (Internal Medicine in the 21st Century). J Intern Med 2000; 247: 615–628.

This paper aims to examine how health telematics will develop in the first 10 years of the new millennium and, in particular, to assess what operational, ethical and legal barriers may lie in the way of this development. A description of the key principles and concepts involved in telemedicine and a short historical overview of telemedicine’s evolution over the past century are followed by consideration of why empirical research into ‘info‐ethics’ and other deontological and legal issues relating to telemedicine is being necessarily catalysed by, amongst others, the European Commission.

Four evolving health telematics applications are examined in some detail: electronic health records; the transmission of visual media in disciplines such as teleradiology, teledermatology, telepathology and teleophthalmology; telesurgery and robotics and the use of call centres and decision‐support software. These are discussed in the light of their moral, ethical and cultural implications for clinicians, patients and society at large.

The author argues that telemedicine presents unique opportunities for both patients and clinicians where it is implemented in direct response to clear clinical needs, but warns against excessive reliance upon technology to the detriment of traditional clinician–patient relationships and against complacency regarding the risks and responsibilities – many of which are as yet unknown – that distant medical intervention, consultation and diagnosis carry.
Geographical differences in the incidence of acute myocardial infarction in Sweden. Analyses of possible causes using two parallel case–control studies
Authors: Hammar N. , Andersson T. , Reuterwall C. , Nilsson T. , Knutsson A. , Hallqvist J. , Ahlbom A.
Published: March 2003

Abstract. Hammar N, Andersson T, Reuterwall C, Nilsson T, Knutsson A, Hallqvist J, Ahlbom A (Karolinska Institutet, Stockholm; Stockholm, Center for Public Health; Västernorrland County Council, Sundsvall; and Norrland University Hospital, Umeå, Sweden). Geographical differences in the incidence of acute myocardial infarction in Sweden. Analyses of possible causes using two parallel case–control studies. J Intern Med 2001; 249: 137–144.

Objectives. To analyse differences in myocardial infarction incidence between two Swedish counties and to evaluate the importance of major risk factors for the observed differences.

Design. The incidence of first myocardial infarction was studied using information from registers. For a number of risk factors of myocardial infarction, the prevalence as well as the relative risk was estimated from population controls of case–control studies in the two areas.

Subjects. Men and women aged 45–64 years in Stockholm and Västernorrland County 1993–94.

Main outcome measures. Relative risks (RRs) and impact fractions were used to evaluate the importance of differences in risk factor prevalence for differences in myocardial infarction incidence between the two areas.

Results. The incidence of first myocardial infarction was higher in Västernorrland than in Stockholm amongst both men (RR = 1.23; 95% CI = 1.08–1.40) and women (RR = 1.41; 95% CI = 1.11–1.79). Obesity and increased levels of blood serum lipids were more prevalent in Västernorrland than in Stockholm amongst men with impact fractions of 6 and 9–11%, respectively. Amongst women, corresponding differences were not seen, but job strain and shift work tended to be more common in the more northern area. Current smoking was more frequent in Stockholm, particularly for women.

Conclusions. The incidence of first myocardial infarction was higher in Västernorrland than in Stockholm in both genders. A higher prevalence of obesity and elevated blood serum lipids may explain, in part, this excess incidence amongst men, but amongst women the causes of the higher incidence in the more northern area remain largely unclear.
Suicide gene therapy: possible applications in haematopoietic disorders
Authors: Dilber M. S. , Gahrton G.
Published: March 2003

Abstract. Dilber MS, Gahrton G (Huddinge University Hospital, Karolinska Institutet, Huddinge, Sweden). Suicide gene therapy: possible applications in haematopoietic disorders (Minisymposium). J Intern Med 2001; 249: 359–367.

Although the treatment results for some forms of haematologic malignancies are excellent, especially for the childhood acute leukaemias, there is still a significant fraction of patients that will not benefit from the therapy available today. The identification of new techniques, such as gene therapy, may therefore be of great importance for future therapeutic applications. Suicide gene therapy is one of several gene therapeutic approaches to treat cancer. A suicide gene is a gene encoding a protein, frequently an enzyme, that in itself is nontoxic to the genetically modified cell. However, when a cell is exposed to a specific nontoxic prodrug, this is selectively converted by the gene product into toxic metabolites that kill the cell. The suicide gene most commonly employed, both in experimental and a clinical settings, is herpes simplex thymidine kinase (HSVtk). Some suicide gene products also induce a so‐called ‘bystander effect’, i.e. a toxic effect on adjacent nongene modified tumour cells and sometimes also on more distant tumour cells. The bystander effect is most evident in tumour cells that have a high number of gap junctions, cellular channels build up by proteins called connexins. Many tumours, amongst them many haematological ones, have a low number of gap junctions. Therefore, it is important to develop gap junction independent drug delivery systems. Suicide gene technology may also be used for the ex vivo purging of tumour cells in bone marrow or peripheral blood stem cell autografts or for inactivation of effector cells, such as antitumour T donor lymphocytes in allogeneic transplantation to prevent severe graft versus host reactions. New constructs, e.g. combining suicide genes and immunresponse enhancing genes or suicide genes and connexin inducing genes may further improve the value of suicide gene therapy.
Specific T‐cell receptor usage with cytokinemia in Henoch–Schönlein purpura nephritis associated with Staphylococcus aureus infection
Authors: Hirayama K. , Kobayashi M. , Muro K. , Yoh K. , Yamagata K. , Koyama A.
Published: March 2003

Abstract. Hirayama K, Kobayashi M, Muro K, Yoh K, Yamagata K, Koyama A (Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba; and Department of Nephrology, Tokyo Medical University Kasumigaura Hospital, Ibaraki, Japan) Specific T‐cell receptor usage with cytokinemia in Henoch–Schönlein purpura nephritis associated with Staphylococcus aureus infection (Original article). J Intern Med 2001; 249: 289–295.

Objectives. We sought to evaluate the mechanism of Henoch–Schönlein purpura nephritis (HSPN) associated with Staphylococcus aureus (S. aureus) infection.

Design. We evaluated six male patients with HSPN associated with S. aureus infection. Routine laboratory examinations, bacteriological examination, histological examination, and analysis of serum cytokine levels were performed in all cases. In addition, peripheral blood mononuclear cells (PBMC) obtained from the six patients and 45 normal individuals were stained with labelled‐monoclonal antibodies against six variable parts of the β‐chain (Vβ) of the T‐cell receptor (TCR), and stained cells were analysed by flow cytometry.

Results. Patients with HSPN associated with S. aureus infection showed features of the nephrotic syndrome with rapidly progressive glomerulonephritis, as well as varying degrees of mesangial proliferative glomerulonephritis with crescent formation. Serological examination showed elevated levels of serum IgA and IgG as well as immune complexes after the onset of infection. The percentage of Vβ‐(5.2 + 5.3) and Vβ 8‐positive cells in patients with HSPN were significantly higher than in normal individuals; moreover, specific TCR‐Vβ usage was not observed in patients with HSPN whose S. aureus infection had improved. Serum levels of IL‐1β, IL‐2, IL‐6, IL‐8 and TNF‐α in patients with HSPN were significantly higher than in normal individuals, and normalized at the healing stage of S. aureus infection.

Conclusion. Conventional antigens and/or staphylococcal enterotoxins originated from S. aureus might have been involved in the pathogenesis of HSPN in the present cohort. Therefore, steroid or other immunosuppressive therapies could not be utilized despite the high activity of glomerulonephritis, and as a result the prognoses of these cases of HSPN were serious.
Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects
Authors: Axelsson T. , Jansson P.‐A. , Smith U. , Eliasson B.
Published: March 2003

Abstract. Axelsson T, Jansson P‐A, Smith U, Eliasson B (Sahlgrenska University Hospital, Göteborg, Sweden). Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects. J Intern Med 2001; 249: 539–544.

Objectives. The aim of this study was to examine if an acute nicotine infusion alters insulin sensitivity to a similar degree in type 2 diabetic patients as in healthy control subjects.

Design. Double‐blind, cross‐over, placebo‐controlled, randomized experimental study. Nicotine 0.3 μg kg–1 min–1 or NaCl was infused (2 h) during a euglycaemic hyperinsulinaemic clamp (4 h) to assess insulin sensitivity.

Setting. University research laboratory.

Subjects. Six male and female type 2 diabetic patients [DM2; age 54 ± 10 (mean ± SD) years; body mass index (BMI) 25.6 ± 2.9 kg m–2] treated with diet or one oral hypoglycaemic agent and six age‐ and BMI‐matched control subjects (Ctr).

Main outcome measures. Insulin sensitivity (rate of glucose infusion per kg fat free body mass and minute), nicotine and free fatty acid (FFA) levels, pulse rate and blood pressure.

Results. The infusions produced similar nicotine levels in both groups. In the absence of nicotine, DM2 were more insulin resistant than Ctr (6.7 ± 0.4 vs. 10.9 ± 0.3 mg kg–1 LBM min–1, respectively; P < 0.0001). This insulin resistance was further aggravated by the nicotine infusion in DM2 but not in Ctr (4.6 ± 0.3 vs. 10.9 ± 0.3 mg kg–1 LBM min–1; P < 0.0001). Only minor differences were seen in FFA levels, pulse rates and blood pressure.

Conclusions. At this low infusion rate, nicotine aggravated the insulin resistance in DM2 but not in Ctr. This finding may be because of the (dysmetabolic) diabetic state per se or to an increased sensitivity to environmental factors associated with a genetic predisposition for type 2 diabetes. These results show that diabetic subjects are particularly susceptible to the detrimental effects of nicotine.
Cost of illness of adult diabetes mellitus underestimated if comorbidity is not considered
Authors: Norlund A. , Apelqvist J. , Bitzén P.‐O. , Nyberg P. , Scherstén B.
Published: March 2003

Norlund A, Apelqvist J, Bitzén P.‐O, Nyberg P, Scherstén (Swedish Council on Technology Assessment in Health Care, Stockholm; and University Hospital; and Dalby/Lund, University of Lund, Lund, Sweden) Cost of illness of adult diabetes mellitus underestimated if comorbidity is not considered.J Intern Med2001;250:57–65.

Objective. To determine costs of illness for adult diabetes mellitus (DM), including complications caused by DM.

Design. A population‐based multicentre cross‐ sectional study including an interview and a physical examination of patients identified as having DM. The patients’ medical records were analysed regarding diagnoses and complications attributable to DM.

Setting. Eight health care centres of six primary care districts in Southern Sweden.

Subjects. 1677 adults aged 25+, cared for at the health care centres, entered the study.

Main outcome measures. Utilization of health care and care from relatives and the municipality, absence of short‐ and long‐term sickness, cost of illness.

Results. The average annual direct and indirect costs for an adult with DM were calculated to be 61 700 Swedish Kronor (SEK) or 2.5 times higher than earlier estimates. The incremental cost of DM was 34 100 SEK. The cost distribution was 28% for health care, 31% for the municipality and relatives and 41% lost productivity.

Conclusions. Calculations for the cost of illness of DM are underestimated if comorbidity caused by DM is not considered. When DM‐related complications are included to identify the actual burden of disease to society, the cost of illness as a result of DM in Sweden is substantially higher than previously estimated.
Prevalence of increased QT interval duration and dispersion in type 2 diabetic patients and its relationship with coronary heart disease: a population‐based cohort
Authors: VEGLIO M. , BRUNO G. , BORRA M. , MACCHIA G. , BARGERO G. , D'ERRICO N. , PAGANO G. F. , CAVALLO‐PERIN P.
Published: March 2003

Abstract. Veglio M, Bruno G, Borra M, Macchia G, Bargero G, D'Errico N, Pagano GF, Cavallo‐Perin P (Evangelico Valdese Hospital, Torino; University of Torino, Torino; and S. Spirito Hospital, Casale Monferrato; Italy). Prevalence of increased QT interval duration and dispersion in type 2 diabetic patients and its relationship with coronary heart disease: a population‐based cohort. J Intern Med 2002; 251: 317–324.

Objective. To evaluate the prevalence of prolonged QT interval and dispersion in a population‐based cohort of type 2 diabetic patients and their relationship with clinical and metabolic variables.

Design. Cross‐sectional population‐based cohort.

Setting. Diabetes clinics and general practitioners in Casale Monferrato (Northern Italy).

Subjects. A total of 1357 patients with known type 2 diabetes (70% of the cohort).

Main outcome measures. Albumin excretion rate and coronary heart disease (CHD); a standard supine 12‐lead electrocardiogram (ECG) was recorded and coded according to the Minnesota code criteria. QT interval corrected for heart rate (QTc) > 0.44 s and QTc dispersion > 0.080 s were considered abnormally prolonged.

Results. Prevalence of increased QTc duration and QTc dispersion were 25.8% (95% CI 23.5–28.3) and 33.1% (95% CI 30.6–35.7), with no sex differences. No metabolic differences were found, apart from fibrinogen and creatinine levels, which were higher in patients with increased QTc dispersion. Patients with CHD had higher mean adjusted values of QTc and QTc dispersion, whereas no association was found with albumin excretion rate (AER) and diabetes treatment. QTc duration and QTc dispersion were significantly correlated (0.17, P < 0.001). In multiple regression analysis, only CHD was independently associated with QTc, after adjustment for age and sex (β=0.010, P < 0.001, R2=2.5%); as regards QTc dispersion, a similar association with CHD was found (β=0.20, P < 0.001, R2=4.8%).

Conclusions. This population‐based study shows a considerably high prevalence of increased QTc and QTc dispersion in type 2 diabetic patients and their association with CHD. These findings have both epidemiological and clinical relevance, as they might be implicated in the excess mortality risk of type 2 diabetic patients.
Cardiovascular prevention before admission reduces mortality following acute myocardial infarction in patients with diabetes
Authors: LÖNDAHL M. , KATZMAN P. , NILSSON A. , LJUNGDAHL L. , PRÜTZ K.‐G.
Published: March 2003

Abstract. Löndahl M, Katzman P, Nilsson A, Ljungdahl L, Prütz K‐G (Helsingborg Hospital, Helsingborg, Sweden). Cardiovascular prevention before admission reduces mortality following acute myocardial infarction in patients with diabetes. J Intern Med 2002; 251: 325–330.

Objectives. Previous studies have shown that patients with diabetes mellitus have an increased mortality after suffering from acute myocardial infarction (AMI). Patients with diabetes have several risk factors for cardiovascular disease. Our objective was to quantify the prevalence of pharmacological cardiovascular prevention at admission and relate such treatment to short and long‐term mortality following AMI in patients with and without diabetes.

Design and subjects. All patients discharged from the Department of Internal Medicine at Helsingborg Hospital in 1996 and 1997 with a principal diagnosis of AMI were included in the study. Patients were divided into two groups according to the presence or absence of diabetes. Cardiovascular risk factors, on‐going medication, type of ward following admission, peak creatine kinase MB mass (CKMB) and immediate treatment were registered. Information about death was obtained from the national register. Kaplan–Meier analysis was performed for life‐expectancy.

Results. A total of 673 patients with AMI were registered, of which 117 (17.4%) had diabetes. No differences in 30 days (17.1% vs. 15.3%) or 1‐year (24.8% vs. 27.4%) mortality were seen between the diabetes and control groups, whereas the 2‐year mortality was significantly higher in the diabetes group (40.2% vs. 29.1%). Cardiovascular risk factors occurred more often in the diabetes group and the use of aspirin, ACE‐inhibitors, statins and diuretics was significantly more frequent. In patients treated with aspirin, in combination with either statin or angiotensin converting enzyme (ACE)‐inhibitor, or both, no differences were seen in 30 days, 1 or 2‐year mortality between groups.

Conclusion. In contrast to earlier studies we did not find an increased 30 days and 1‐year mortality in patients with diabetes suffering from AMI. This discrepancy was linked to a higher frequency of pharmacological cardiovascular prevention, a finding supporting the hypothesis that survival of a diabetes patient after AMI could be affected by factors operating before the infarction.
Muscle strength, Na,K‐pumps, magnesium and potassium in patients with alcoholic liver cirrhosis – relation to spironolactone
Authors: AAGAARD N. K. , ANDERSEN H. , VILSTRUP H. , CLAUSEN T. , JAKOBSEN J. , DØRUP I.
Published: March 2003

Abstract. Aagaard NK, Andersen H, Vilstrup H, Clausen T, Jakobsen J, Dørup I (University of Aarhus, Aarhus, Denmark). Muscle strength, Na, K‐pumps, magnesium and potassium in patients with alcoholic liver cirrhosis – relation to spironolactone. J Intern Med 2002; 252: 56–63.

Objectives. To evaluate the muscle strength in relation to muscle contents of magnesium (Mg), potassium (K) and sodium, potassium (Na,K)‐pumps in patients with alcoholic cirrhosis.

Design. An open cross‐sectional study.

Setting and subjects. Fifty‐one consecutive patients with liver cirrhosis admitted to the Department of Hepatology, Aarhus University Hospital, Denmark, and 28 age‐ and sex‐matched healthy control subjects.

Main outcome measures. Biopsies of skeletal muscle were performed in patients and controls for measurements of Mg, K, and Na,K‐pumps. Furthermore, maximum isokinetic knee extension and skeletal muscle mass were evaluated.

Results. Muscle mass, muscle strength, muscle Mg and muscle K were substantially reduced in the patients (P < 0.01, all), and fell with increasing severity of the liver disease reflected in the Child‐Pugh (C‐P) class. Patients treated with spironolactone for 2 weeks or more, had increased muscle strength, muscle Mg and content of Na,K‐pumps, compared with the rest of the patients (P < 0.05, all). In a multivariate analysis of the patients, skeletal muscle mass, muscle Mg and daily alcohol consumption (g) were independent predictors of isokinetic muscle strength (P < 0.05, all).

Conclusions. Patients with alcoholic liver cirrhosis showed considerably reduced muscle strength and muscle Mg was an independent predictor of muscle strength. Surprisingly, in the spironolactone treated patients, muscle weakness was less pronounced, possibly because of the action of spironolactone on muscle Mg, K and Na,K‐pump content.
Invasive pulmonary aspergillosis resulting in respiratory failure during neutrophil recovery from postchemotherapy neutropenia in three patients with acute leukaemia
Authors: Takuma T. , Okada K. , Uchida Y. , Yamagata A. , Sawae Y.
Published: March 2003

Abstract. Takuma T, Okada K, Uchida Y, Yamagata A, Sawae Y (Kyushu University Graduate School of Sciences, Fukuoka, Japan; University of California, CA, USA; and Shin‐kokura Hospital, Fukuoka, Japan). Invasive pulmonary aspergillosis resulting in respiratory failure during neutrophil recovery from postchemotherapy neutropenia in three patients with acute leukaemia (Case Report). J Intern Med 2002; 252: 173–177.

Respiratory failure is a severe complication of invasive pulmonary aspergillosis (IPA). Its pathogenesis is not well understood. We herein describe three cases of subacute respiratory failure that occurred during the recovery phase of neutropenia following induction chemotherapy for acute leukaemia with IPA. In each case, severe neutropenia (19–85 days), high‐grade fever, severe anaemia, the use of granulocyte‐colony‐stimulating factor and increasing infusion volume were noted. As the neutrophil count was recovering, the shadows on the chest X‐ray expanded with progressing hypoxia. We should pay attention to the respiratory failure during the recovery phase of neutropenia in patients with IPA.
Adrenal incidentaloma – experience of a standardized diagnostic programme in the Swedish prospective study
Authors: Bülow B. , Ahrén B. ,   the Swedish Research Council Study Group of Endocrine Abdominal Tumours
Published: March 2003

Abstract  Bülow B, Ahrén B (Lund University, Lund, Sweden) on behalf of the Swedish Research Council Study Group of Endocrine Abdominal Tumours. Adrenal incidentaloma – experience of a standardized diagnostic programme in the Swedish prospective study. J Intern Med 2002; 252: 239–246.

Objective.  To report the 5‐year experience of a diagnostic programme for adrenal incidentaloma with special emphasis to diagnose hormonally active and malignant lesions.

Design.  A prospective study in which new cases of adrenal incidentalomas in Sweden have been evaluated by a standardized diagnostic protocol between January 1996 and July 2001.

Setting.  Thirty‐three different Swedish hospitals have contributed with cases.

Subjects.  A total of 381 patients (217 females, 164 males) with adrenal incidentalomas were studied.

Interventions.  Diagnostic procedures were undertaken according to a standardized programme. Operation was recommended if the incidentaloma had a size of more than 3–4 cm or if there was a suspicion of a hypersecreting tumour.

Main outcome measures.  The size of the incidentaloma, clinical characteristics of the patients and results of biochemical diagnostic tests were registered.

Results.  The median age of the patients was 64 years (18–84 years), and the median size of the incidentalomas was 3 cm (1–20 cm). A total of 85(22%) patients were operated. Twenty of thesepatients were diagnosed with a benign hypersecreting tumour and 14 with a malignant tumour. Fourteen of 15 operated patients with diagnosed pheochromocytoma had elevated 24‐h urinary noradrenaline and all of the patients operated because of a biochemical suspicion of aldosterone or cortisol hypersecretion (n = 6) were found to have adrenal adenomas. Of the 14 operated patients with malignant diseases, 10 were adrenal carcinomas (median size 10 cm; range 4–16 cm). In a multiple logistic regression model, incidentaloma size was significantly associated with the risk of a malignant tumour (P = 0.009), and there was a tendency of an association between age/male sex and the risk of a malignancy (both, P = 0.07).

Conclusion.  In this Swedish multicentre study of 381 cases with adrenal incidentalomas, 5% had benign hypersecreting tumours and nearly 4% had malignant tumours. The results of the biochemical diagnostic tests used had a high compatibility with the histological diagnosis found at operation in the patients with hypersecreting tumours. Tumour size, male gender and high age were predictive for the risk of a malignant tumour. A follow‐up of the patients is warranted in order to establish whether there are undiscovered cases of malignant or hypersecreting tumours amongst the nonoperated patients.
Endothelium‐dependent flow‐mediated vasodilatation, insulin resistance and the metabolic syndrome in 60‐year‐old men
Authors: Wendelhag I. , Fagerberg B. , Hulthe J. , Bokemark L. , Wikstrand J.
Published: March 2003

Objectives.  To evaluate the endothelium‐dependent flow‐mediated vasodilatation (FMD) in the brachial artery and to study the relationship to insulin sensitivity and to the metabolic syndrome in 60‐year‐old clinically healthy men.

Subjects.  The men were randomly selected from the general population (n = 55). The subjects with the metabolic syndrome were defined according to a definition proposed by a working group associated with the World Health Organization (WHO).

Methods.  Ultrasound images for measurement of lumen diameter of the brachial artery were recorded before and after reactive hyperaemia induced by occlusion of the artery, both with and without ischaemic hand exercise during the occlusion. Insulin‐mediated glucose uptake was determined by euglycaemic hyperinsulinaemic clamp as a measure of insulin sensitivity.

Results.  The FMD was in the total group 3.2% when hyperaemia was induced by occlusion only and 8.7% after occlusion plus ischaemic hand exercise (P < 0.001, n = 51). However, no relationship was observed between any measure of FMD and insulin‐mediated glucose uptake (r = −0.05 and r = 0.06, n = 47, P > 0.30). Furthermore, subjects with the metabolic syndrome (n = 13) did not differ in any measure of FMD compared with those with no risk factors (n = 11).

Conclusion.  In this study the ultrasound method to evaluate endothelial function did not show that low insulin sensitivity or the metabolic syndrome were associated with impaired FMD in otherwise clinically healthy 60‐year‐old men.