bluuebunny/crossref_metadata_2025 huggingface dataset:
Attitudes of Japanese students toward people with intellectual disability
Authors: Horner‐Johnson W. , Keys C. , Henry D. , Yamaki K. , Oi F. , Watanabe K. , Shimada H. , Fugjimura I.
Published: March 2003

Background

The purpose of the present study was to gain insight into the structure and organization of the attitudes of Japanese students toward people with intellectual disability (ID). The study also examined how these attitudes are related to individual characteristics, such as experience with people with ID, major field of study and career interests.

Methods

The participants completed a series of measures developed in the USA: three measures of attitudes toward people with ID, a demographic questionnaire and a social desirability scale. Students completed the measures anonymously.

Results

The factor structures of all three attitude scales replicated the structures found in the USA. Attitudes toward the community inclusion of people with ID were negatively correlated with an endorsement of eugenics. Students in social work and psychology had more positive attitudes than other students. Participants who expressed an interest in a career working with people with ID had more positive attitudes than students with no interest in such a career.

Conclusions

Attitude measures developed in the USA can be used in Japan, and can provide useful information as well as an opportunity for cross‐cultural comparisons. For a more complete understanding of the attitudes of Japanese people toward people with ID, these attitudes should also be studied using measures based in Japanese culture which have specifically developed to measure attitudes in Japan.
Recovery from Marie‐Bamberger's syndrome and diabetes insipidus after removal of a lung adenocarcinoma with neuroendocrine features
Authors: El‐Salhy  , Simonsson  , Stenling  , Grimelius
Published: March 2003

El‐Salhy M, Simonsson M, Stenling R, Grimelius L (University Hospital, Umeå; and University Hospital, Uppsala; Sweden). Recovery from Marie‐Bamberger's syndrome and diabetes insipidus after removal of a lung adenocarcinoma with neuroendocrine features (Case Report). J Intern Med 1998; 243: 171–75

A 44‐year‐old woman with Marie‐Bamberger's syndrome and diabetes insipidus had a lung tumour with mediastinal metastases, but no signs of metastases to the hypothalamus or pituitary gland. A week after removal of the tumour, the joint pain, polyuria and polydipsia disappeared. The tumour was diagnosed histopathologically as a moderately differentiated adenocarcinoma with focal neuroendocrine cell differentiation and dispersed cells reacting with antisera against neurone‐specific enolase, S‐100 protein, neuropeptide Y, follicle‐stimulating hormone, substance P, vasoactive polypeptide (VIP), adrenocortirotropic hormone and pancreatic polypeptide (PP) as well as to one of three tested antisera raised against antidiuretic hormone (ADH). It was suggested that Marie‐Bamberger's syndrome might be caused by one of these immunoreactive substances or by a substance that shares an amino acid sequence with one of these neuroendocrine peptides. It was also suggested that the tumour might produce an ADH‐like substance which might have an ADH‐antagonist effect.
The ultimate biochemical diagnosis of endocrine pancreatic tumours in MEN‐1
Authors: Öberg  , Skogseid
Published: March 2003

Öberg K, Skogseid B (University Hospital, Uppsala, Sweden). The ultimate biochemical diagnosis of endocrine pancreatic tumours in MEN‐1 (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 471–6.

Multiple endocrine neoplasia type 1 (MEN‐1) is a well characterized hereditary syndrome with the occurrence of primary hyperparathyroidism (HPT) in combination with pancreatic‐duodenal endocrine and anterior pituitary tumours. The diagnosis of MEN‐1, the possible probands, necessitates the recognition of at least two or three lesions classically associated with the syndrome whilst only one of them is required for individuals belonging to established MEN‐1 kindreds. A distinct feature of MEN‐1 comprises the multiplicity of organ involvement, the multicentricity of tumours within the affected organs as well as the complex pattern of the clinical signs of these tumours and their sometimes temporarily variable profile of hormone excess. Thorough screening studies have demonstrated that the MEN‐1 trait is biochemically detectable virtually two decades prior to clinically overt disease. The primary biochemical screening programme for MEN‐1 includes serum prolactin and insulin growth factor 1 (IGF‐1) for pituitary lesions, intact PTH and albumin corrected total serum calcium for the parathyroids and for duodenal/pancreatic tumours serum glucose, insulin, proinsulin, pancreatic polypeptide, glucagon, gastrin and plasma chromogranin A. Furthermore a standardized meal stimulatory test analysing serum polypeptides (PP) and gastrin is recommended. Our current primary screening procedure has yielded about 10% false positives when compared with RFLP data. Pancreatic endocrine tumour diagnosis must be biochemically established since radiology fails to show lesions in half of the patients. Pancreatic involvement in young MEN‐1 patients is most consistently demonstrated by analysing serum insulin, proinsulin, PP as well as plasma glucagon chromogranin A levels, which have exhibited sensitivities of 56, 67, 37 and 60%, respectively. Serum PP is a non‐specific marker of islet cell tumours that should be applied in conjunction with other peptide markers. Elevation of basal serum gastrin generally indicates the presence of advanced pancreatic tumour involvement or duodenal carcinoids. Early diagnosis of pancreatic endocrine tumours in MEN‐1 is enhanced by the use of a standardized meal stimulation test with measurements of serum PP and gastrin response. This test was the most sensitive test and substantiated the presence of tumour in 75% of individuals whose mean age was 25 years. False‐positive stimulation due to the meal test has been found in about 10% of previous investigated individuals. The diagnosis of MEN‐1 pancreatic tumours is based on biochemical screening alone and it has been substantiated that an unequivocal rise in pancreatic tumour markers precedes radiological detection of these lesions by at least five years.
Low frequency of the common Norwegian and Finnish LDL‐receptor mutations in Swedish patients with familial hypercholesterolaemia
Authors: Lind S. , Eriksson M. , Rystedt E. , Wiklund O. , Angelin B. , Eggertsen G.
Published: March 2003

. Lind S, Eriksson M, Rystedt E, Wiklund O, Angelin B, Eggertsen G (Karolinska Institute at Huddinge University Hospital, Stockholm, Sahlgren's Hospital, Göteborg, Sweden). Low frequency of the common Norwegian and Finnish LDL‐receptor mutations in Swedish patients with familial hypercholesterolaemia. J Intern Med 1998: 244: 19–25.

Objective

. To evaluate the frequency of the common Finnish and Norwegian mutations in the low density lipoprotein (LDL) receptor gene in Swedish patients with familial hypercholesterolaemia (FH), and to start screening for other mutations in these patients. In contrast to the situation in Norway and Finland, where the frequency of common mutations causing the disease has been determined, very little about the mutation spectrum is known in Sweden.

Settings and subjects

. In total, 182 unrelated Swedish patients fulfilling clinical criteria for FH were investigated. Of these, 112 were identified at Huddinge University Hospital in Stockholm, and 70 at Sahlgren's Hospital in Göteborg. They were screened by single‐strand conformation polymorphism (SSCP) for mutations in exons 3, 4, 6 and 9 of the LDL‐receptor gene and by polymerase chain reaction (PCR) for the most common FH mutations occurring in Finland, and the prevailing mutation causing familial defective apolipoprotein B‐100 (FDB).

Results

. Mutations in the LDL receptor were identified in 25 of the 182 patients. Of these, 10 represented FH‐Helsinki and one FH‐North Karelia. Other mutations identified were FH‐Svartor (four patients), FH‐Elverum (one patient), FH‐Padova (two patients), FH‐Morocco (one patient) and FH‐Algeria‐1 (one patient). One patient was simultaneously positive for two mutations formerly described in Sweden: E256K (exon 6) and I402T (exon 9). Another mutation caused replacement of one amino acid residue in exon 6 (C292Y). Two new mutations were found, both in exon 6: one nonsense mutation in the codon #275 for cysteine (FH‐Huddinge, two patients), and one deletion of two base‐pairs in the codon for leucine in position 254 (FH‐Göteborg, one patient). The mutation for FDB was found in three patients.

Conclusions

. The mutation pattern in Swedish FH patients differs considerably from that in Finland and Norway. The two new mutations discovered will probably cause serious functional disturbances in the LDL‐receptor function. Thus far, no predominant mutation was seen in Swedish FH‐patients.
Familial multiple endocrine neoplasia syndromes: components, classification, and nomenclature
Authors: Carney
Published: March 2003

Carney JA (Mayo Clinic and Mayo Foundation, Rochester, MN, USA). Familial multiple endocrine neoplasia syndromes: components, classification, and nomenclature (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 425–32.

There are three generally accepted multiple endocrine neoplasia (MEN) syndromes: MEN‐1, MEN‐2A, and MEN‐2B. On the basis of their major features, new familial MEN syndromes should manifest (i) a new endocrine tumour combination, (ii) autosomal dominant inheritance, and, possibly, (iii) a nonendocrine component. Acceptance of the last feature as a criterion has conferred candidate MEN status on a number of disorders, including von Hippel–Lindau disease and neurofibromatosis. To regard these conditions as MEN syndromes would require an inappropriate demotion of their predominant nonendocrine manifestations. The role of nonendocrine disorders in MEN syndromes needs reappraisal.
Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first‐line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery
Authors: Lindgren A. , Lindgren A. , Lindstedt G. , Kilander A. F.
Published: March 2003

Lindgren A, Lindstedt G, Kilander AF (Borås Central Hospital and Sahlgrenska University Hospital, Göteborg, Sweden). Advantages of serum pepsinogen A combined with gastrin or pepsinogen C as first‐line analytes in the evaluation of suspected cobalamin deficiency: a study in patients previously not subjected to gastrointestinal surgery. J Intern Med 1998; 244: 341–349.

Objectives

Since there is a significant overlap in serum cobalamin concentrations between healthy and cobalamin‐deficient individuals, we wanted to compare two different principles for use as supplementary tests to serum cobalamin concentration in patients with suspected cobalamin malabsorption and deficiency.

Design

Clinical study of consecutive patients.

Setting

The catchment area of Sahlgrenska University Hospital, Göteborg.

Subjects

A total of 112 patients with suspected cobalamin deficiency who had not previously undergone gastrointestinal surgery.

Interventions

Gastroduodenoscopy with biopsies taken from the gastric body and the duodenum, Schilling test, and measurement of serum methylmalonic acid (MMA), total homocysteine (Hcy), pepsinogens A and C, and gastrin.

Main outcome measures

Number of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin.

Results

About 95% of the patients with severe gastric body atrophy had abnormal concentrations of serum pepsinogen A and/or gastrin or pepsinogen A/C ratio, whereas 65% had abnormal metabolite concentrations. Serum pepsinogen A combined with pepsinogen C identified 100%, and combined with gastrin 88%, of the patients with gastric body atrophy and elevated metabolite tests, and 67 and 75%, respectively, of those who had not yet developed elevated metabolite tests.

Conclusions

Pepsinogen A, combined with pepsinogen C or gastrin, should be the first option in evaluating patients with suspected cobalamin deficiency who have not previously undergone gastrointestinal surgery.
Fibrinogen and mortality in chronic critical limb ischaemia
Authors: Pedrinelli R. , Dell Omo G. , Barchielli A. , Berchiolli R. , Melillo E. , Mariani M. , Balbarini A. , Ferrari M.
Published: March 2003

Objective. Plasma fibrinogen predicts cardiovascular events in patients with stable peripheral arterial occlusive disease, but its predictive value in patients with chronic critical limb ischaemia, a condition associated with a high risk of death, is unknown.

Design. A prospective cohort study.

Setting. Determination of fibrinogen and other potential predictors during clinic‐based work‐up of patients admitted for diagnostic and therapeutic evaluation.

Subjects. A total of 108 patients (72 ± 10 years, 78 males) with atherosclerotic occlusive disease and critical limb ischaemia (pain at rest and/or trophic lesions) followed up for a median period of 1.6 years (range: 8 days–5.5 years; 218 patient‐years).

Main outcome measures. Total mortality.

Results. Forty‐five deaths (71% cardiovascular) occurred during the follow‐up. Baseline fibrinogen was higher in those who died in the early follow‐up period (first 6 months), as were white cell count and serum creatinine, while haematocrit was lower. Plasma fibrinogen values correlated positively with white cell count, and negatively with haematocrit; other cardiovascular prognostic factors did not differ. Only plasma fibrinogen predicted survival independently in multivariate age‐corrected Cox regression analysis. Relative risk of death doubled for each standard deviation above the mean and increased with each tertile increase in fibrinogen.

Conclusions. Fibrinogen predicted death in these elderly arteriopaths with critical limb ischaemia, particularly those who died in the first months following critical ischaemia. Inflammatory stimuli secondary to severely defective tissue oxygenation and possibly sepsis and necrosis, might have stimulated fibrinogen, an acute‐phase reactant, thereby compromising organ perfusion through increased blood viscosity and/or promoting thrombosis.
Genetically engineered mice in drug development
Authors: Livingston J. N.
Published: March 2003

Abstract. Livingston JN (Bayer Corporation, West Haven, CT, USA). Genetically engineered mice in drug development. (Minisymposium: Genes & Obesity). J Intern Med 1999; 245: 627–635.

Complex metabolic diseases like type 2 diabetes (noninsulin‐dependent diabetes) and obesity present a difficult challenge to pharmaceutical companies in their attempts to develop new therapies. The polygenic nature of these diseases and the influence of nongenetic factors make it difficult to identify the most critical molecular processes to target for drug development. Transgenic animal models provide an approach to evaluate specific sites in metabolic and hormone signalling pathways under physiologic (as opposed to in vitro) conditions. The advantages and limitations of using transgenic animals in drug development will be covered and an overview of recent information from transgenic studies relevant to type 2 diabetes and obesity will be given.
A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible?
Authors: Andreev E. , Koopman M. , Arisz L.
Published: March 2003

Abstract. Andreev E, Koopman M, Arisz L (Medical University‐Sofia, Sofia, Bulgaria and University of Amsterdam, Amsterdam, The Netherlands). A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible? (Review.) J Intern Med 1999; 246: 247–252.

This is a review of the available information about drugs which cause an increase in plasma creatinine concentration without decreasing glomerular filtration rate (GFR). The GFR is the main, but not the single, determinant of the plasma creatinine levels. Several drugs, such as cimetidine, trimethoprim, corticosteroids, pyrimethamine, phenacemide, salicylates and active vitamin D metabolites, have been reported to increase plasma creatinine without influencing its glomerular filtration. Cimetidine, trimethoprim, pyrimethamine and salicylates can inhibit secretion of creatinine by the proximal tubule. Corticosteroids and vitamin D metabolites probably modify the production rate and the release of creatinine. The exact mechanism of phenacemide–creatinine interaction is not fully explained. These drug‐induced alterations in plasma creatinine concentration have clinical significance when GFR is estimated by using plasma creatinine.
The cost of inappropriate admissions: a study of health benefits and resource utilization in a department of internal medicine
Authors: Eriksen B. O. , Kristiansen I. S. , Nord E. , Pape J. F. , Almdahl S. M. , Hensrud A. , Jæger S.
Published: March 2003

Abstract. Eriksen BO, Kristiansen IS, Nord E, Pape JF
, Almdahl SM, Hensrud A, Jæger
S (University Hospital of Tromsø and University of Tromsø, Tromsø; National Institute of Public Health, Oslo; Kommunelegekontoret i Bardu, Bardu; and Nordland Central Hospital, Bodø, Norway). The cost of inappropriate admissions: a study of health benefits and resource utilization in a department of internal medicine. J Intern Med 1999; 246: 379–387.

Objectives. High rates of inappropriate hospital admissions have been found in numerous studies, suggesting that a high percentage of hospital resources are, in effect, wasted. The degree to which this is true depends on how costly inappropriate admissions are compared to other admissions. This study aimed to estimate both the percentage and cost of inappropriate admissions.

Setting. Department of internal medicine at a teaching hospital.

Subjects. Consecutively admitted patients during a six‐week study period.

Main outcome measures.
Assessments of inappropriateness were based on estimates of health benefit and necessary care level. These estimates were made by expert panels using a structured consensus method. Health benefit was estimated as gain in quality‐adjusted life years, or degree of short‐term improvement in quality of life during or shortly after the hospital stay. The direct costs to the hospital of each stay were estimated by allocating the costs of labour, ‘hotel’ and overhead according to length of stay and adding to this the cost of ancillary resources used by each individual patient.

Results. A total of 422 admissions were included. The 102 (24%) judged to be inappropriate had a lower mean cost (US$ 2532) than the other 320 (US$ 5800) (difference 3268; 95% confidence interval 1025–5511). The inappropriate admissions accounted for 12% of the total costs.

Conclusions. Denying care for inappropriate admissions does not generate cost reductions of the same magnitude. Policy makers should be cautious in projecting the cost savings potential of excluding inappropriate admissions.
Postprandial lipoprotein metabolism and atherosclerosis
Authors: Karpe F.
Published: March 2003

Abstract. Karpe F. (Karolinska Hospital, Stockholm, Sweden; and Radcliffe Infirmary, Oxford, England, UK). Postprandial lipoprotein metabolism and atherosclerosis (Review). J Intern Med 1999; 246: 341–355.

Postprandial lipids and lipoproteins have been associated with the presence of cardiovascular disease in a large number of case‐control studies. Because the metabolic perturbations around the postprandial situation is a key driving force for cholesterol flux between lipoproteins and tissues, together with the augmented generation of potentially atherogenic cholesterol‐rich remnant lipoproteins, several hypotheses have been formulated to link excessive lipoproteinaemic response to fat intake with cardiovascular disease. Recent information on the regulation of lipoprotein remnant formation and its relation to atherosclerosis will enable us to test a pertinent clinical question: is there a direct relationship between repeated elevations of postprandial lipoproteins and development of atherosclerosis?
Cross‐sectionally assessed carotid intima–media thickness relates to long‐term risk of stroke, coronary heart disease and death as estimated by available risk functions
Authors: Bots M. L. , Hoes A. W. , Hofman A. , Witteman J. C. M. , Grobbee D. E.
Published: March 2003

Objective. To relate cross‐sectionally assessed indicators of carotid atherosclerosis measured in participants of the Rotterdam Study to absolute 10–12 year risks of stroke, coronary heart disease and death estimated by risk functions available from other studies.

Setting. General population living in the suburb of Ommoord in Rotterdam, The Netherlands.

Subjects. A sample of men and women (n = 1683), aged 55 years or over, drawn from participants from the Rotterdam Study (n = 7983).

Main outcomes measures. Three risk scores were used to estimate for each individual the absolute risk of stroke, coronary heart disease and death within 10–12 years as a function of their cardiovascular risk factor profile. Cross‐sectionally measured indicators of carotid atherosclerosis (presence of atherosclerotic lesions and common carotid intima–media thickness) were subsequently related to these risk scores.

Results. The 10‐year absolute risk of stroke increased linearly from 4.8% (95%CI = 3.8, 5.8) for subjects in the lowest quintile to 16.1% (12.3, 21.9) for subjects in the highest quintile of common carotid intima–media thickness distribution. Similarly, the 10‐year absolute risk for coronary heart disease rose from 13.1% (95%CI = 12.0, 14.2) to 23.4% (95%CI = 21.4, 25.4), whereas the risk of death within 11.5 years rose from 15.0% (95%CI = 12.8, 17.4) in the lowest quintile to 46.0% (42.8, 49.3) in the upper quintile. The absolute risks of stroke, coronary heart disease or death rose from 8.8, 15.8 and 26.9% to 14.3, 19.8 and 40.9%, respectively, when plaques in the common carotid artery were present. Similar findings were observed for plaques in the carotid bifurcation.

Conclusion. Common carotid intima–media thickness and carotid plaques are markers for increased risk of stroke, coronary heart disease and death within 10–12 years.
Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases
Authors: Papadopoulos K. I. , Melander O. , Orho‐Melander M. , Groop L. C. , Carlsson M. , Hallengren B.
Published: March 2003

Abstract. Papadopoulos KI, Melander O, Orho‐Melander M, Groop LC, Carlsson M, Hallengren B (University of Lund, Malmö University Hospital, Malmö, Sweden). Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases. J Intern Med 2000; 247: 71–77.

Objectives. To investigate the significance of ACE gene insertion/deletion (I/D) polymorphism in the frequency of autoimmune manifestations in sarcoidosis.

Design. In patients with sarcoidosis the ACE gene I/D polymorphism was detected with PCR on genomic DNA. The patients with sarcoidosis were divided according to the presence (n = 30) or absence (n = 32) of autoimmune manifestations. The former group was subdivided into thyroid autoimmunity (n = 10), gluten immune reactivity (n = 10) and gastric autoimmunity (n = 17).

Settings. The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden.

Subjects. Sixty‐two patients with documented sarcoidosis (30 females, 32 males, median age/range at diagnosis of sarcoidosis 31.5/19–75 years, median age/range at study 47.5/22–81 years) were examined. A total of 107 healthy unrelated subjects without sarcoidosis (60 females, 47 males, median age/range at study 58/40–82 years) served as controls.

Results. S‐ACE values were significantly increased in patients compared to controls (P = 0.00001). The same was true in the subgroup of sarcoidosis patients with associated autoimmunity compared with those with isolated sarcoidosis (P = 0.0328). A significant association was seen between ACE gene polymorphism (II, ID, DD genotypes) and S‐ACE levels in both patients and controls according to the order II < ID < DD. The observed genotype frequency distributions in the different study groups agreed the Hardy–Weinberg equilibrium without significant differences between the patients and the controls. Within the group with autoimmune manifestations the DD genotype was significantly over‐represented in X‐ray stage III compared to the other X‐ray stages (P = 0.0181) and a significant increase in the DD genotype in X‐ray stage III (P = 0.035) in the group with autoimmune manifestations compared to isolated sarcoidosis was detected.

Conclusion. We confirmed that the S‐ACE levels corresponded to the order II < ID < DD in patients with sarcoidosis as well as in healthy controls. S‐ACE levels were significantly higher in sarcoidosis patients with autoimmune manifestations. The frequency of the DD genotype was significantly increased in patients with autoimmune manifestations and major granuloma mass (X‐ray stage III). The ACE D allele in its homozygous form may confer susceptibility for autoimmune manifestations in sarcoidosis, possibly via the high levels of S‐ACE it encodes.
Left ventricular calcification following resuscitation
Authors: Lapatto‐Reiniluoto O. , Vaalamo M. , Takkunen O. , Mänttäri M.
Published: March 2003

Abstract. Lapatto‐Reiniluoto O, Vaalamo M, Takkunen O, Mänttäri M (Helsinki University Central Hospital, Helsinki, Finland). Left ventricular calcification following resuscitation (Case Report). J Intern Med 2000; 248: 85–87.

In this paper we report a case of 34‐year‐old man with a severe septic shock. Because of profound hypotension he was given massive amounts of catecholamines for 10 days. After a short recovery the function of his heart started to deteriorate again and clear calcification around the left ventricle was disclosed by computer tomography. Catecholamines are known to induce myocardial injury resulting in a special form of cardiomyopathy with eventual calcification, but there are no previous reports of myocardial calcification to this extent.
Coronary artery disease and arterial hypertension: clinical, angiographic and follow‐up data
Authors: Natali A. , Vichi S. , Landi P. , Toschi E. , Severi S. , L’Abbate A. , Ferrannini E.
Published: March 2003

Abstract. Natali A, Vichi S, Landi P, Toschi E, Severi S, L’Abbate A, Ferrannini E (C.N.R. Institute of Clinical Physiology and the University of Pisa, Pisa, Italy). Coronary artery disease and arterial hypertension: clinical, angiographic and follow‐up data. J Intern Med 2000; 247: 219–230.

Objectives. To evaluate how the presence of arterial hypertension affects coronary atherosclerosis and prognosis in patients with, or at high risk of, ischaemic heart disease.

Design. Retrospective analysis of clinical records and follow‐up data.

Settings. Single referral centre for ischaemic heart disease.

Subjects. All consecutive patients (n = 1700, 38% with hypertension) undergoing coronary angiography for the evaluation of ischaemic heart disease during 1983–92.

Results. On angiography, the likelihood of having three‐vessel disease was higher amongst hypertensives (odds ratio = 1.41; 95% confidence interval [CI] = 1.08–1.85) after adjustment for age, sex, and angina symptoms. The sum of all visible stenoses (an index of overall atherosclerotic involvement) was 19% higher in hypertensives (262 ± 204 vs. 220 ± 194 units, P < 0.005). By multivariate analysis, the presence of hypertension made a modest (+ 28 units), albeit statistically significant, independent contribution to the total atherosclerosis score. On follow‐up (median = 96 months), cardiovascular mortality was slightly higher in the hypertensive patients than in the normotensive group (P < 0.05 in a Kaplan–Meier analysis), but a proportional hazard analysis adjusting for age and gender showed no significant independent contribution of hypertension. Hypertensive patients, however, remained at higher risk of non‐fatal myocardial infarction following discharge (adjusted odds ratio = 1.21, 95% CI = 1.03–1.46; P < 0.05).

Conclusions. In this referral population, hypertension is a risk factor for presence of three‐vessel disease. Distribution, severity and extension of coronary stenosis are similar to those of normotensive patients, and prognosis is only marginally affected.
Impaired leukotriene C4 generation in granulocytes from protein‐energy malnourished chronically ill elderly
Authors: Cederholm T. , Lindgren J. Å. , Palmblad J.
Published: March 2003

Abstract. Cederholm T, Lindgren JÅ, Palmblad J (Centre for Hematology and Inflammatory Research, Huddinge University Hospital and Karolinska Institutet, Stockholm, Sweden). Impaired leukotriene C4 generation in granulocytes from protein‐energy malnourished chronically ill elderly. J Intern Med 2000; 247: 715–722.

Objective. The dysregulation of the immune and inflammatory systems observed in protein‐energy malnutrition (PEM) may be partly due to perturbation of essential fatty acid metabolism. In this study, we assessed the calcium ionophore A23187‐induced generation of the arachidonate metabolites leukotriene B4 (LTB4) and leukotriene C4 (LTC4) in isolated granulocyte suspensions.

Design. Case–control study.

Setting. A university‐affiliated acute care hospital in urban Stockholm.

Subjects. Fourteen severely malnourished elderly subjects with stable non‐malignant disorders (age 74 ± 1 years, mean ± SEM) and 12 healthy age‐matched controls were examined.

Main outcome measures. Leukotrienes were analysed by high‐performance liquid chromatography. Body mass index (BMI, kg m–2) and delayed cutaneous hypersensitivity (DCH) reaction were determined.

Results. BMI was 16.5 ± 0.5 and 26.2 ± 0.9 kg m–2 (mean ± SE) in the malnourished group and controls (P < 0.001), respectively. DCH was 8.5 mm (median) in patients and 29.5 mm in controls (P < 0.001). LTC4 generation in granulocytes from PEM patients was half of that of controls (9.1 ± 2.0 vs. 17.8 ± 5.2 pmol mL–1, P < 0.05) when cells were stimulated with 0.2 µmol L–1 of A23187, and 13.7 ± 2.5 and 27.2 ± 7.5 pmol mL–1, respectively (NS), upon stimulation with 1.0 µmol L–1 of A23187. LTB4 production in PEM patients and controls did not differ at any of the two calcium ionophore concentrations. LTC4 production correlated with BMI (r = 0.41, P < 0.05), but there was no significant correlation between DCH and LTB4 or LTC4 production.

Conclusion. Protein‐energy malnutrition is accompanied by perturbation of leukotriene synthesis, which may be one factor underlying the dysregulation of inflammatory responses in the depleted patient.
LDL particle size in relation to intima‐media thickness and plaque occurrence in the carotid and femoral arteries in patients with hypercholesterolaemia
Authors: Hulthe J. , Wiklund O. , Bondjers G. , Wikstrand J.
Published: March 2003

Abstract. Hulthe J, Wiklund O, Bondjers G, Wikstrand J (Sahlgrenska University Hospital, Göteborg University, Gothenburg, Sweden). LDL particle size in relation to intima‐media thickness and plaque occurrence in the carotid and femoral arteries in patients with hypercholesterolaemia. J Intern Med 2000; 248: 42–52.

Objectives. Small LDL particle size has been shown to be associated with coronary artery disease. However, no previous study has been performed relating LDL particle size to ultrasound measurement of atherosclerosis in hypercholesterolaemic subjects. The main aims of the present study were therefore: (i) to investigate the relationship between intima‐media thickness (IMT) of the carotid bulb and LDL particle size in patients with primary hypercholesterolaemia (n = 102) and in matched normocholesterolaemic controls (n = 102); and (ii) to investigate the relationship between plaque occurrence in the carotid and femoral arteries and LDL particle size. LDL particle size was determined by subjecting serum to 2–16% polyacrylamide gradient gel electrophoresis.

Results. The results showed that patients with primary hypercholesterolaemia had smaller LDL peak particle size compared with healthy control subjects (P < 0.001 for men, P = 0.006 for women). However, the difference in LDL peak particle size between patients with hypercholesterolaemia and controls disappeared when adjusting for serum triglycerides. There was no association between increasing IMT of the carotid bulb and decreasing LDL peak particle size or between the occurrence of moderate to large plaques in the carotid and femoral arteries and small LDL peak particle size. However, metabolic variables such as serum triglycerides, HDL, blood glucose, body mass index, and also systolic blood pressure were associated with LDL peak particle size.

Conclusion. The lack of an association between atherosclerosis, as measured by ultrasound, and small LDL particle size in patients with hypercholesterolaemia implies that other risk factors, such as hypercholesterolaemia and high blood pressure, may overshadow any importance of small LDL particle size.
Increased bone mineral density in a population‐based group of 70‐year‐old women on thiazide diuretics, independent of parathyroid hormone levels
Authors: Sigurdsson G. , Franzson L.
Published: March 2003

Sigurdsson G, Franzson L (University Hospital, Fossvogur, Reykjavik, Iceland). Increased bone mineral density in a population‐based group of 70‐year‐old women on thiazide diuretics, independent of parathyroid hormone levels (Original Article). J Intern Med 2001; 250: 51–56.

Background. Several studies have shown greater bone mineral density (BMD) in people receiving thiazide diuretics compared with controls. Most researchers have related this association to the hypocalciuric effect of thiazides with subsequent rise in serum calcium and fall in parathyroid hormone (PTH) levels. Recent experimental evidence suggests, however, a direct effect of thiazides on osteoblast‐like cells.

Objective. To test the hypothesis that the association of thiazides and raised BMD is independent of PTH levels in humans.

Subjects. A population‐based group of 248 70‐year‐old Icelandic women, 51 receiving thiazide diuretics, 39 receiving other antihypertensive therapy and the rest acting as controls.

Main outcome measures. The independent contribution of thiazide usage and PTH to BMD in a multivariate analysis.

Results. The mean BMD was 9.6% greater in the lumbar spine (P < 0.01) and 5.4% greater in the whole skeleton (P < 0.01) amongst thiazide users than in controls, reduced to 7.6% (P < 0.02) and 4.5% (P < 0.01), respectively, when corrected for fat mass which was 5.8 kg greater in the thiazide group. In a multivariate analysis, corrected for body weight and body composition, serum calcium and ln‐PTH, thiazides remained a significant independent predictor of BMD in the total skeleton and lumbar spine, but not in the total hip or femoral neck. Thiazides explained about 3% of the variability in whole body and lumbar spine BMD.

Conclusions. Thiazides augment or preserve BMD independent of PTH, implying other mechanisms.
Episodes of ST‐segment depression is related to changes in ambulatory blood pressure and heart rate in intermittent claudication
Authors: Svensson P. , Niklasson U. , Östergren J.
Published: March 2003

Abstract. Svensson P, Niklasson U, Östergren J (Karolinska Hospital, Stockholm, Sweden). Episodes of ST‐segment depression is related to changes in ambulatory blood pressure and heart rate in intermittent claudication. J Intern Med 2001; 250: 398–405.

Objective. To study the prevalence and circadian distribution of ischaemic ST‐segment depression detected with ambulatory electrocardiographic monitoring (AECG) in patients with intermittent claudication (IC) as well as to study ambulatory blood pressure (ABP) and the relation of ischaemic episodes to variations in ABP and heart rate.

Design. A total of 40 patients with a history of IC and an ankle/brachial‐index (ABI) <0.9 performed: (i) 24‐h AECG recordings, (ii) simultaneous 24 h recordings of ABP every 15 min (Spacelabs 90207), (iii) an exercise treadmill test (ETT). An ischaemic episode was defined as a transient ischaemic ST‐segment deviation ≥1 mm lasting >1 min. Eleven patients were excluded from ECG analysis because of uninterpretable ECG caused by treatment with digoxin or technical problems.

Results. Out of 29 patients, eight experienced a total of 15 episodes of ST‐depression on AECG. The mean duration was 21 ± 31 min. The majority of episodes (11 of 15) occurred between 6 and 12 a.m. In eight patients with ST‐segment depression three had a history of ischaemic heart disease (IHD), four were hypertensives and four had signs of myocardial ischaemia on ETT. There were no significant differences between patients with and without ST‐segment depression in ABP, walking performance or ABI. During ST‐depression episodes systolic and diastolic blood pressure and heart rate were higher than day mean values; 178 ± 41 vs. 166 ± 30 mmHg (P=0.09); 96 ± 9 vs. 90 ± 4 mmHg (P=0.01) and 103 ± 9 vs. 87 ± 5 beats min–1 (P < 0.01).

Conclusion. Silent myocardial ischemia occurred in about a third of patients with IC. Episodes of ischaemia were associated with an increased ABP and heart rate. Whether treatment of high blood pressure may reduce silent ischaemia and if this favourably influences outcome is a matter of further research.
Urinary albumin excretion is independently associated with C‐reactive protein levels in overweight and obese nondiabetic premenopausal women
Authors: Pannacciulli N. , Cantatore F. P. , Minenna A. , Bellacicco M. , Giorgino R. , De Pergola G.
Published: March 2003

Abstract. Pannacciulli N, Cantatore FP, Minenna A, Bellacicco M, Giorgino R, De Pergola G (Section of Internal Medicine, Endocrinology and Metabolic Diseases and Section of Rheumatology, University of Bari, Bari, Italy). Urinary albumin excretion is independently associated with C‐reactive protein levels in overweight and obese nondiabetic premenopausal women. J Intern Med 2001; 250: 502–507.

Objectives. C‐reactive protein (CRP) and microalbuminuria are nowadays considered markers of chronic inflammation of the arterial wall and of endothelial dysfunction, respectively. An increase of CRP levels and of urinary albumin excretion (UAE) rate have both been reported to be independently associated with a higher risk of cardiovascular morbidity and mortality in the general population. The aim of the present study was to evaluate the possible correlation between UAE and CRP concentrations in overweight and obese premenopausal women.

Design and setting. A cross‐sectional study in a primary care setting.

Subjects, main outcome measures. CRP levels and UAE rate were measured in 103 overweight and obese premenopausal women, aged 18–45 years. Other measurements included: central fat accumulation, as evaluated by waist circumference; insulin resistance, as calculated by homeostatic model assessment (HOMAIR); fat‐free mass (FFM), as measured by bioimpedance analysis; blood pressure; and fasting plasma levels of glucose, insulin, and lipids.

Results. Urinary albumin excretion was positively correlated with body mass index (BMI) (P < 0.01), waist circumference (P < 0.001), diastolic blood pressure (P < 0.01), triglycerides (P < 0.01), HOMAIR (P < 0.05), and CRP levels (P < 0.05); and negatively associated with HDL cholesterol (P < 0.001). After multivariate analysis, diastolic blood pressure, HDL cholesterol, and CRP levels maintained their significant correlation with UAE.

Conclusion. Our study shows a strong relationship between UAE and CRP concentrations, irrespective of age and other anthropometric and metabolic variables. On this basis, it can be argued that inflammation of the arterial wall, as indicated by higher CRP plasma levels, and endothelial dysfunction, as shown by higher UAE rate, might represent simultaneous phenomena in the development of atherosclerosis in overweight and obese premenopausal women.
Haemochromatosis: Understanding the mechanism of disease and implications for diagnosis and patient management following the recent cloning of novel genes involved in iron metabolism
Authors: Fletcher L. M. , Halliday J. W.
Published: March 2003

Abstract. Fletcher LM, Halliday JW (The Princess Alexandra Hospital; and The Queensland Institute of Medical Research, Queensland, Australia). Haemochromatosis: understanding the mechanism of disease and implications for diagnosis and patient management following the recent cloning of novel genes involved in iron metabolism (Review). J Intern Med 2002; 251: 181–192.

Haemochromatosis, a common recessive genetic disorder in people of Northern European descent, is an iron storage disorder characterized by excessive hepatic iron accumulation resulting from disruption of the regulation of intestinal iron absorption. The identification of novel genes involved in the control of iron absorption from the diet has allowed improved understanding of iron metabolism in health and disease. In particular, the identification of the haemochromatosis gene (HFE) and more recently the transferrin receptor 2 gene (TfR2) together with the specific mutations in these genes which result in hepatic iron overload, has enhanced our understanding of the pathophysiology of haemochromatosis. However, because of the wide variation in phenotypic expression of the disease, there now exists a considerable challenge to diagnosis and patient management.
Angiotensin‐converting enzyme gene polymorphism in relation to HLA‐DR in sarcoidosis
Authors: Planck A. , Eklund A. , Yamaguchi E. , Grunewald J.
Published: March 2003

Abstract. Planck A, Eklund A, Yamaguchi E, Grunewald J. (Karolinska Hospital, Stockholm, Sweden; and Hokkaido University School of Medicine, Sapporo, Japan). Angiotensin‐converting enzyme gene polymorphism in relation to HLA‐DR in sarcoidosis. J Intern Med 2002; 251: 217–222.

Objectives. To investigate if an insertion/deletion (I/D) polymorphism in the angiotensin‐converting enzyme (ACE) gene associates with HLA‐DR alleles previously found to be of prognostic interest in Scandinavian sarcoidosis patients. This may contribute to characteristics associated with these HLA‐DR alleles, such as a good (DR17) or poor (DR14 or 15) prognosis.

Design, settings and subjects. Polymerase chain reaction (PCR) was used for analysing an I/D polymorphism in the gene coding for ACE in 138 subjects; 65 controls and 73 sarcoidosis patients, and for HLA‐DR genotyping 67 patients. Serum ACE level (S‐ACE) was measured in all controls and 72 patients. Sixty‐one patients were classified as chronic or nonchronic after 2 years follow‐up. All patients were recruited and followed at our outpatient clinic.

Results. No significant differences in ACE alleles or genotypes were seen between controls and patients or between patients positive and negative for DR17 or DR14/15. The ACE genotype did not differ between nonchronic and chronic patients. The ACE genotype tended to influence the S‐ACE in patients, whilst in controls S‐ACE significantly differed between the ACE genotypes.

Conclusion. This study does not support an association between ACE genotype and sarcoidosis or disease outcome. However, because significantly (P < 0.001) more DR17 positive (17 of 19) than DR14/15 positive (seven of 26) patients were classified as nonchronic, these results instead strengthen the prognostic importance of HLA‐DR alleles in Scandinavian sarcoidosis patients.
Perioperative myocardial infarction in noncardiac surgery: the diagnostic and prognostic role of cardiac troponins
Authors: LUCREZIOTTI S. , FORONI C. , FIORENTINI C.
Published: March 2003

Abstract. Lucreziotti S, Foroni C, Fiorentini C (Università degli Studi di Milano, Ospedale S. Pado, Milano, Italy). Perioperative myocardial infarction in noncardiac surgery: the diagnostic and prognostic role of cardiac troponins (Review). J Intern Med 2002; 252: 11–20.

Despite the number of technologies used, the diagnosis of perioperative myocardial infarction is still a challenge. Studies conducted in surgical series have demonstrated that cardiac troponins (cTns) have both a superior diagnostic sensitivity and specificity, compared with other traditional techniques, and an independent power to predict short‐ and long‐term prognosis. Nevertheless, some points need to be clarified. They include the usefulness of cTns in patients with end‐stage renal failure; the standardization of the cTns cut‐off for the diagnosis of myocardial injury; the timing of postoperative blood samplings; the cost‐effectiveness of a screening in asymptomatic patients; and the possible therapeutic strategies.
Vitamin B‐12 treatment has limited effect on health‐related quality of life among individuals with elevated plasma methylmalonic acid: a randomized placebo‐controlled study
Authors: Hvas A.‐M. , Juul S. , Nexø E. , Ellegaard J.
Published: March 2003

Abstract.  Hvas A‐M, Juul S, Nexø E, Ellegaard J (Aarhus University Hospital, Aarhus, Denmark). Vitamin B‐12 treatment has limited effect on health‐related quality of life among individuals with elevated plasma methylmalonic acid: a randomized placebo‐controlled study. J Intern Med 2003; 253: 146–152.

Objective.  To examine the hypothesis that treatment with vitamin B‐12 improves health‐related quality of life (HRQOL) in individuals with biochemical signs of vitamin B‐12 deficiency.

Design.  A randomized placebo‐controlled study.

Setting.  Municipality of Aarhus, Denmark.

Subjects.  Nonhospitalized individuals (n = 140) with a modest increase in plasma methylmalonic acid (0.40–2.00 μmol L−1) not previously treated with vitamin B‐12.

Intervention.  The participants were randomized to vitamin B‐12 injection treatment or placebo weekly for 4 weeks and re‐examined 3 months later. The investigator and the participants were blinded to the intervention.

Main outcome measure.  Change in HRQOL assessed by the SF‐36 questionnaire from baseline to follow‐up examination 3 months later.

Results.  The participants reported a significantly worser HRQOL than the age‐ and sex‐matched Danish general population (P < 0.001). However, no change was observed after treatment with vitamin B‐12 for seven of eight health dimensions. A significant improvement was found only in general health when compared with the placebo group (P = 0.03).

Conclusions.  Vitamin B‐12 treatment influenced only one of eight dimensions of HRQOL amongst participants with biochemical signs of vitamin B‐12 deficiency. We therefore question the benefit of vitamin B‐12 treatment amongst elderly with a modestly increased plasma methylmalonic acid as the only sign of vitamin B‐12 deficiency.