bluuebunny/crossref_metadata_2025 huggingface dataset:
Life expectancy of people with intellectual disability: a 35‐year follow‐up study
Authors: Patja K. , Iivanainen M. , Vesala H. , Oksanen H. , Ruoppila I.
Published: March 2003

A 35‐year follow‐up study based on a nation‐wide population study of the life expectancy of people with intellectual disability (ID) was undertaken. The study population consisted of a total of 60969 person‐years. A prospective cohort study with mortality follow‐up for 35 years was used and the life expectancy of people with ID was calculated for different levels of intelligence. Proportional hazard models were used to assess the influence of level of intelligence and associated disorders on survival. People with mild ID did not have poorer life expectancy than the general population and subjects with mild ID did not have lower life expectancy in the first 3 decades of life. In cases with profound ID, the proportion of expected life lost was > 20% for almost all age groups. The female preponderance was manifested from the age of 60 years onwards, 25 years later than in the general population. Respectively, survival between sexes differed less. Epilepsy and/or hearing impairment increased the relative risk of death for all levels of ID. The prevalence of people with ID over 40 years was 0.4%. People with ID now live longer than previously expected, and the ageing of people with mild ID appears to be equal to that of the general population, posing new challenges to health care professionals.
Sedation effects on responsiveness: evaluating the reduction of antipsychotic medication in people with intellectual disability using a conditional probability approach
Authors: Smith C. , Felce D. , Ahmed Z. , Fraser W. I. , Kerr M. , Kiernan C. , Emerson E. , Robertson J. , Allen D. , Baxter H. , Thomas J.
Published: March 2003

Background

The impact of the withdrawal of long‐term antipsychotic medication prescribed to adults with intellectual disabilities on behavioural functioning has been investigated using a real‐time direct observation methodology. Previous authors have reported a significant post‐reduction difference in engagement in activity between the successful drug reduction and control groups.

Method

In the present study, sequential analysis of the relationship between staff:resident interaction and behavioural engagement was used to give a more precise measure of the extent to which user responsiveness is affected by drug withdrawal. Responsiveness was measured by calculating the likelihood of engagement occurring given the occurrence of staff interaction. This likelihood was represented by the statistic Yule's Q‐value.

Results

High Yule's Q‐value results pre‐ and post‐baseline were found, indicating that clients were highly responsive to staff interaction. However, Yule's Q‐value did not significantly increase following drug withdrawal.

Conclusion

The present study provides no evidence of greater responsiveness following the withdrawal of psychotropic medication.
Life satisfaction of people with intellectual disability living in community residences: perceptions of the residents, their parents and staff members
Authors: Schwartz C. , Rabinovitz S.
Published: March 2003

Background Within the literature on quality of life (QoL), life satisfaction (LS) has emerged as a key variable by which to measure perceived well‐being, which is referred to as subjective QoL. The LS self‐reports of 93 residents with intellectual disability (ID) living in community‐based residences were compared with reports about their LS completed by their staff and parents.

Method The residents were interviewed on their LS by social workers who did not belong to the staff of the interviewee's residence. The instrument used was the Life Satisfaction Scale (LSS). Staff and parents completed the short version of the LSS.

Results Residents and staff's LS reports were positively correlated. However, significant differences were found between these two groups of informants when the residents were characterized as high functioning, had a low score in challenging behaviour, worked in an integrative employment setting and lived in an apartment. As opposed to staff/resident discrepancies, no differences were found between parents’ and residents’ LS reports.

Conclusions If residents cannot to be interviewed about their LS, then the parent is the preferred person to respond on behalf of the resident. The current study highlights the importance of including both objective measures (e.g. functional assessment characteristics) and subjective measures (e.g. LS) in order to get a better understanding of the QoL of people with ID.
Magnetic resonance imaging, Down's syndrome and Alzheimer's disease: research and clinical implications
Authors: Prasher V. , Cumella S. , Natarajan K. , Rolfe E. , Shah S. , Haque M. S.
Published: March 2003

BackgroundThe diagnosis of Alzheimer's disease (AD) remains at times difficult to make using available neuropsychological measures. Neuro‐imaging is a relatively new form of detecting the changes associated with dementia. The present study investigated the role of magnetic resonance imaging (MRI) in diagnosing AD in adults with Down's syndrome (DS).

MethodsSubjects with DS and Alzheimer‐type dementia were matched to non‐demented controls with DS. Magnetic resonance imaging findings (i.e. volumetric and two‐dimensional scans) were compared between the two groups in order to show a relationship between the changes of AD and structural MRI abnormalities.

ResultsSpecific structural abnormalities which are seen in non‐intellectually disabled subjects with dementia are also found in individuals with both DS and AD. However, such findings cannot be used to diagnose clinical AD with good accuracy in adults with DS. A number of practical issues of patient compliance and over‐sedation are demonstrated by the findings.

ConclusionsMagnetic resonance imaging has an important but limited role to play in the management of AD in the population with DS. If intravenous sedation is used, medical support is essential to prevent a serious mishap.
Low molecular weight heparin‐induced skin necrosis occurring distant from injection sites and without thrombocytopenia
Authors: Tietge  , Schmidt  , JÄckel  , Trautwein
Published: March 2003

Tietge UJF, Schmidt HH‐J, Jäckel E, Trautwein C, Manns MP (Medizinische Hochschule Hannover, Hannover, Germany). Low molecular weight heparin‐induced skin necrosis occurring distant from injection sites and without thrombocytopenia (Case Report). J Intern Med 1998; 243: 313–15.

In this paper we report a case of 76‐year‐old white male patient with skin necrosis induced by subcutaneous prophylactic administration of low‐molecular‐weight heparin (LMWH). Skin necrosis occured distant from heparin injection sites and without concomitant thrombocytopenia. This is the first reported case presenting these clinical findings.
Association of multiple endocrine neoplasia type 2 and Hirschsprung disease
Authors: Romeo  , Ceccherini  , Celli  , Priolo  , Betsos  , Bonardi  , Seri  , Yin  , Lerone  , Jasonni  , Martucciello
Published: March 2003

Romeo G, Ceccherini I, Celli J, Priolo M, Betsos N, Bonardi G, Seri M, Yin L, Lerone M, Jasonni V, Martucciello G (University of Genoa Medical School, Genoa, Italy; International Agency for Research on Cancer, Lyon, France). Association of multiple endocrine neoplasia type 2 and Hirschsprung disease (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 515–20.

In a few patients with Hirschsprung disease (HSCR) and no clinical symptoms of multiple endocrine neoplasia type 2 (MEN‐2A) or medullary thyroid carcinoma (MTC), missense mutations in the cysteine residues 609 and 620 of the Ret gene have been identified. In several pedigrees with either MEN‐2A or familial MTC (FMTC) a documented germline mutation in cysteine 618 or 620 follows the segregation of the disease phenotype. The appearance of the HSCR phenotype in such patients and pedigrees cannot be easily reconciled with the gain of function which is associated with the dominant oncogenic effect of MEN‐2A mutations. Gastrointestinal manifestations are known to occur also in association with MEN‐2B but, to the best of our knowledge, in only very few cases the intestinal phenotype of MEN‐2B has been investigated by enzymo‐histochemical techniques, as in the present work. We report an extensive molecular study of patients, two with HSCR and FMTC carrying a Cys620Arg or Ser mutation and two with MEN‐2B and gastrointestinal symptoms carrying a Met918Thr mutation. One of the latter two patients showed aganglionosis of the last 5 cm of rectum which caused a congenital megacolon leading to the diagnosis and operation for HSCR. The mutation screening of all the exons of Ret in 3 of these patients did not reveal any additional mutation. Therefore these results do not support the hypothesis of additional constitutional Ret mutations in patients showing association of MEN‐2 and HSCR, whilst the histochemical and clinical data in one of these patients indicate that MEN‐2B can be associated with a true form of short segment HSCR.
The spectrum of hepatobiliary disease in primary hypogammaglobulinaemia
Authors: Bjøro K. , Haaland T. , Skaug K. , Frøland S. S.
Published: March 2003

Objective.  To study the prevalence of hepatobiliary disease in a clinically and immunologically well‐characterized group of 88 adult Norwegian patients with primary hypogammaglobulinaemia.

Subjects.  Eighty‐eight patients with primary hypogammaglobulinaemia were followed and signs and symptoms of liver disease were recorded. The patients were examined clinically and radiologically on a regular basis with liver biopsies performed when indicated. All patients were tested for hepatitis C virus (HCV) RNA, hepatitis G virus (HGV) RNA and hepatitis B virus (HBsAg).

Results.  Twenty‐one patients were HCV RNA‐positive, all having signs of chronic liver disease. Only four patients were HGV RNA‐positive, of whom two were also HCV RNA‐positive. Amongst the 67 HCV RNA‐negative patients, 26 had signs of chronic liver disease, including two who were HGV RNA‐positive. HCV RNA‐negative patients with liver disease had received intravenous immune globulin substitution more frequently, had a longer history of any form of immune globulin substitution and had a greater incidence of common variable immunodeficiency than patients without signs of liver disease. In most cases (21 of 26 patients) the liver disease was relatively mild. Three patients had granulomatous liver disease, with a relatively aggressive course in all three.

Conclusion.  Hepatobiliary disease is a frequent complication in primary hypogammaglobulinaemia. Liver disease in HCV RNA‐negative patients usually has a mild course. HGV does not seem to be a major cause of chronic liver disease in these patients.
Leptin and its potential role in human obesity
Authors: Lönnqvist F. , Nordfors L. , Schalling M.
Published: March 2003

Abstract. Lönnqvist F, Nordfors L, Schalling M (Karolinska Institute at Huddinge University Hospital and Karolinska Hospital, Stockholm, Sweden). Leptin and its potential role in human obesity. (Minisymposium: Genetics & Obesity). J Intern Med 1999; 245: 643–652.

Genetic studies in inbred obese mice have revealed the ob gene, its product leptin and the leptin receptor as important factors in the regulation of both appetite and energy expenditure. Treatment with recombinant leptin has resulted in a marked weight reduction in obese animals with ob gene mutations as well as in normal mice. Also mutations in the Ob receptor gene result in marked obesity in rodents. These data have given hope of new treatment options in obesity. Further support of leptin being involved in regulation of obesity in man comes from the observation that inactivating mutations in the human ob gene lead to profound early onset obesity. However, the role of leptin and its feedback system in man is still only partly revealed. This review focuses on our present knowledge and hypotheses about the leptin pathway in humans and its potential importance in the clinic of obesity.
Adrenoceptor genes in human obesity
Authors: Arner P. , Hoffstedt J.
Published: March 2003

Abstract. Arner P, Hoffstedt J (Karolinska Institute, Huddinge Hospital, Stockholm, Sweden). Adrenoceptor genes in human obesity. (Minisymposium: Genes & Obesity). J Intern Med 1999; 245: 667–672.

The genes causing obesity in rodent models have been characterized, but do not seem to be important for human obesity. Recently the putative association between obesity and polymorphism in human beta‐adrenergic receptor genes have been studied intensely in the light of the important role of these receptors in the regulation of energy mobilization and utilization. A polymorphism (Trp64Arg) in the beta3‐adrenergic receptor gene is associated with obesity (relative risk ≈ 2) in some but not all investigations on Caucasian and Japanese populations. When expressed in artificial cell systems, the polymorphism is associated with alterations of the beta3‐adrenoceptor. The genetic allele variance influences also the native receptor function when measured in isolated human fat cells. The human beta2‐adrenoceptor gene shows a high degree of polymorphism. The role of beta2‐receptor gene polymorphism for obesity has so far only been investigaed in women. A Gln27Glu variant is markedly associated with obesity with a relative risk for obesity of ≈ 7 and odds ratio of ≈ 10. Women who are homozygous for 27Glu have ≈ 20 kg higher fat mass than controls. Thus, polymorphism in genes coding for different beta‐adrenoceptor subtypes may be important for the development of human obesity.
Menopausal status and risk factors for cardiovascular disease
Authors: Peters H. W. , Westendorp I. C. D. , Hak A. E. , Grobbee D. E. , Stehouwer C. D. A. , Hofman A. , Witteman J. C. M.
Published: March 2003

Abstract Peters HW, Westendorp ICD, Hak AE, Grobbee DE, Stehouwer CDA, Hofman A, Witteman JCM (Erasmus University Medical School, Rotterdam; Utrecht University, Utrecht; Vrije Universiteit, Amsterdam, The Netherlands). Menopausal status and risk factors for cardiovascular disease. J Intern Med 1999; 246: 521–528.

Objectives. Changes in cardiovascular risk factors with menopausal status are difficult to study, owing to the high correlation of menopausal status with age. Therefore we examined cardiovascular risk factors in a meticulously selected population in which the contrast in oestrogen status between pre‐ and postmenopausal women of the same age was maximized.

Design. Risk factors were compared in 93 premenopausal and 93 postmenopausal women who were matched on age (range 43–55 years).

Setting. The women were selected from respondents to a mailed questionnaire about the menopause, which was sent to all women aged 40–60 years in the Dutch town of Zoetermeer (n = 12 675; response 54%).

Subjects. Postmenopausal women who were at least 3 years after menopause or whose menses had stopped naturally before age 48 were age‐matched with premenopausal women with regular menses and without menopausal complaints.

Results. Compared to premenopausal women, postmenopausal women had significantly increased levels of total cholesterol (10.0%, 95% confidence interval 5.1–14.0), low density lipoprotein (LDL) cholesterol (14.0%, 6.9–19.9), and apolipoprotein B (8.2%, 0.6–15.5). The difference was present within 3 years after onset of menopause and did not show a trend towards an increase with the number of postmenopausal years. No differences were found in high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1, blood glucose, insulin, body mass index, waist‐to‐hip ratio, and systolic and diastolic blood pressure.

Conclusions. The results of this study add to the evidence that total cholesterol, LDL cholesterol and apolipoprotein B are the primary cardiovascular risk factors affected by menopause.
Recurrent malignant hypertension: a report of two cases and review of the literature
Authors: Spencer C. G. C. , Lip G. Y. H. , Beevers D. G.
Published: March 2003

Abstract. Spencer CGC, Lip GYH, Beevers DG (City Hospital, Birmingham, UK). Recurrent malignant hypertension: a report of two cases and review of the literature (Case Report). J Intern Med 1999; 246: 513–516.

Malignant hypertension (MHT) is a rare and life‐threatening condition which is defined clinically as severe hypertension accompanied by bilateral retinal haemorrhages and/or hard exudates, with or without papilloedema. If untreated, the prognosis of MHT is poor. With MHT being a relatively rare condition, it would be unusual to see it on more than one occasion in the same patient. We describe in detail two cases from a disease register of 400 cases of MHT seen in one medical centre over 33 years.
Influence of protease inhibitor therapy on lipoprotein metabolism
Authors: Berthold H. K. , Parhofer K. G. , Ritter M. M. , Addo M. , Wasmuth J. C. , Schliefer K. , Spengler U. , Rockstroh J. K.
Published: March 2003

Abstract. Berthold HK, Parhofer KG, Ritter MM, Addo M, Wasmuth JC, Schliefer K, Spengler U, Rockstroh JK (University of Bonn and University of Munich, Germany). Influence of protease inhibitor therapy on lipoprotein metabolism. J Intern Med 1999; 246: 567–575.

Objectives. Protease inhibitors are efficient drugs as part of highly active antiretroviral therapy. They have been shown to cause hyper‐ and dyslipoproteinemia. Since antiretroviral therapy is able to delay disease progression and possibly extend life expectancy in HIV‐infected individuals, the precise nature of serum lipid disturbances may become of clinical interest with respect to its atherogenicity and to finding treatment options.

Design. We investigated prospectively, in 19 subsequent HIV‐positive male patients (mean age 42 ± 13 years), multiple lipid parameters in plasma, before and during treatment with a protease inhibitor (nelfinavir, ritonavir, or indinavir) and two nucleoside analogue reverse transcriptase inhibitors (NRTI). The median (range) treatment duration was 22 (7–40) weeks. 12 patients were treatment‐naive; 7 had already NRTI medication at baseline.

Results. Total cholesterol increased by 28 mg dL–1 (95% CI: + 7 to + 48, baseline 158 ± 53, P = 0.01), triglycerides increased by 96 mg dL–1 (+ 22 to + 170, baseline 152 ± 91, P = 0.014), HDL cholesterol was unchanged, LDL cholesterol was slightly but not significantly elevated, VLDL cholesterol increased by 20 mg dL–1 (+ 9 to + 31, baseline 33 ± 21, P = 0.001), VLDL triglycerides increased by 86 mg dL–1 (+ 22 to + 150, baseline 128 ± 91, P = 0.01). The ratio of total cholesterol to HDL cholesterol increased by 1.2 (+ 0.7 to + 1.7, baseline 4.8 ± 1.5, P = 0.0001) and the ratio of HDL2 to HDL3 decreased by 0.06 (–0.02 to –0.09, baseline 0.47 ± 0.11, P = 0.005). (Conversion factors, mg dL–1 to mmol L–1: 0.0259 for cholesterol, 0.0114 for triglycerides.)

Conclusions. The data indicate that the predominant feature of dyslipidemia under protease inhibitors is an increase in triglyceride‐containing lipoproteins. This observation is in accordance with the hypothesis of increased apoptosis of peripheral adipocytes, release of free fatty acids and subsequent increased synthesis of VLDL. The lipid profile, based on the ratio of total cholesterol to HDL cholesterol and the ratio HDL2 to HDL3, is significantly more atherogenic.
Effects of diabetes mellitus on patients with acute intermittent porphyria
Authors: Andersson C. , Bylesjö I. , Lithner F.
Published: March 2003

Objectives. To study the effects of diabetes mellitus in patients with acute intermittent porphyria (AIP).

 Haeme deficiency in the liver of AIP patients stimulates an increase in ALA‐synthase which triggers an escalating metabolic chain reaction, leading to an increase in the porphyrin content. This reaction can be reduced by treating AIP patients with haeme arginate or with glucose.

Design. A population‐based study of all patients >18 years of age having DNA‐verified AIP (n = 328) living in the two most northerly counties of Sweden (Norrbotten and Västerbotten, with 550 000 inhabitants) of whom 16 had type 2 diabetes. Prevalence of diabetes was studied retrospectively in 26 AIP patients with hepatocellular carcinoma (HCC).

Results. None of the patients showed symptoms of AIP after the onset of their diabetes. Three patients had had recurrent, severe attacks for many years but when their diabetes became manifest, their urinary ALA and PBG levels decreased and the AIP symptoms resolved, to the relief of the patients. Amongst the 26 AIP patients with HCC, only one with signs of diabetes was identified (impaired glucose tolerance test).

Conclusions. This study raises the possibility that diabetes mellitus may be beneficial for patients with severe AIP.
Tissue‐type plasminogen activator and C‐reactive protein in acute coronary heart disease. A nested case–control study
Authors: Gram J. , Bladbjerg E.‐M. , Møller L. , Sjøl A. , Jespersen J.
Published: March 2003

Abstract. Gram J, Bladbjerg E‐M, Møller L, Sjøl A, Jespersen J (Department of Clinical Biochemistry, Ribe County Hospital and the Institute for Thrombosis Research, South Jutland University Centre, Esbjerg, and the Centre of Preventive Medicine, Glostrup University Hospital; Denmark). Tissue‐type plasminogen activator and C‐reactive protein in acute coronary heart disease. A nested case–control study. J Intern Med 2000; 247: 205–212.

Objectives. To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects.

Design. Nested case‐control study. Follow‐up periods 7–15 years.

Subjects. Included in the study were 133 cases with coronary heart disease and 258 controls.

Interventions. None.

Main outcome measures. Subjects with ischaemic heart disease identified in 1991 by the Danish National Hospital Register. Protein concentration of C‐reactive protein (CRP) and tissue‐type plasminogen activator (t‐PA) were measured with ELISA methods in stored serum samples.

Results. CRP and t‐PA concentrations were both significantly higher in cases than in controls (P < 0.001 and P < 0.001). This difference between cases and controls for CRP and t‐PA was present in both men (CRP: P = 0.022; t‐PA: P = 0.001) and women (CRP: P = 0.013; t‐PA: P = 0.005) and it was present in both the 7–9 years follow‐up cohort (CRP: P = 0.014; t‐PA: P = 0.001) and the 15 years follow‐up cohort (CRP: P = 0.027; t‐PA: P = 0.012). The best predictor of CRP was t‐PA, whilst the best predictor of t‐PA was triglycerides. In a logistic regression analysis model, t‐PA still came out as independent predictor of coronary heart disease, whilst such a significance disappeared for CRP. With the use of ROC curves we determined that AUC for t‐PA was 0.62, and for CRP 0.59, indicating that none of these two analytes has a high prognostic power in predicting future coronary events in an initially healthy population.

Conclusion. We conclude that moderate increases in serum concentrations of CRP and t‐PA are present for up to 15 years before the presence of clinical overt coronary heart disease; that a low‐grade inflammation is determined by other risk factors and that t‐PA is an independent risk factor for evolution of coronary heart disease.
Hepatitis C virus risk: a hepatitis C virus related syndrome
Authors: Mazzaro C. , Panarello G. , Tesio F. , Santini G. , Crovatto M. , Mazzi G. , Zorat F. , Tulissi P. , Pussini E. , Baracetti S. , Campanacci L. , Pozzato G.
Published: March 2003

Abstract. Mazzaro C, Panarello G, Tesio F, Santini G, Crovatto M, Mazzi G, Zorat F, Tulissi P, Pussini E, Baracetti S, Campanacci L, Pozzato G (Pordenone General Hospital, Pordenone; University of Trieste, School of Medicine, Trieste, Italy). Hepatitis C virus risk: a hepatitis C virus‐related syndrome. J Intern Med 2000 247: 535–545.

Background. The association between mixed cryoglobulinemia (MC) and hepatitis C virus (HCV) infection has been recently described in many reports.

Objective. The aim of this study was to evaluate the long‐term prognosis of hepatitis C virus‐positive patients affected by mixed cryoglobulinemia with or without kidney involvement.

Patients. At total of 119 hepatitis C virus‐positive patients affected by mixed cryoglobulinemia were divided in two groups. Group A: mixed cryoglobulinemia without kidney involvement (103 cases); group B: mixed cryoglobulinemia with glomerulonephritis (GN) (16 cases). A further 37 patients affected by mesangio‐proliferative glomerulonephritis (MPGN) were evaluated as controls (group C).

Methods. Anti‐hepatitis C virus antibodies were determined by commercial kits and hepatitis C virus‐RNA was detected by polymerase chain reaction (PCR) amplification of the 5′ untranslated region (5′UTR) of the virus. The hepatitis C virus genotype was determined according to Okamoto. Liver biopsy was performed in 62 patients, bone marrow biopsy in 65 patients, and kidney biopsy in all patients with proteinuria.

Results. In group A, 46 patients (45%) were affected by chronic liver disease (CLD), 21 (20%) by low‐grade non‐Hodgkin’s lymphoma (NHL) and 16 (15%) by both diseases. All patients of group B were affected by type I membrano‐proliferative glomerulonephritis, 3 (19%) by chronic liver disease, 6 (37%) by low‐grade non‐Hodgkin’s lymphoma, and 7 (44%) by both diseases. Several genotypes of hepatitis C virus were found, but Type 1b was prevalent. In group C, no patient showed chronic liver disease or non‐Hodgkin’s lymphoma. Younger age, higher mean blood pressure, lower C4 serum level, and poorer survival significantly distinguished group B from group A. Survival rates at 5 years were: 87.4% for group A, 89.5% for group C, and 50.0% for group B. None of the patients of group B developed kidney failure requiring dialysis, whilst infections were the leading cause of death.

Conclusions. In hepatitis C virus‐positive patients, the presence of mixed cryoglobulinemia associated with kidney involvement seems to indicate a new syndrome characterized by immune system impairment, lack of progression to kidney failure, and poor survival (hepatitis C virus‐Risk syndrome).
The Q/E27 polymorphism in the β2‐adrenoceptor gene is associated with increased body weight and dyslipoproteinaemia involving triglyceride‐rich lipoproteins
Authors: Ehrenborg E. , Skogsberg J. , Ruotolo G. , Large V. , Eriksson P. , Arner P. , Hamsten A.
Published: March 2003

Abstract. Ehrenborg E, Skogsberg J, Ruotolo G, Large V, Eriksson P, Arner P, Hamsten A (Karolinska Hospital, Stockholm, and Huddinge University Hospital, Huddinge, Sweden; and Istuto Scientifico H San Raffaele, Milano, Italy). The Q/E27 polymorphism in the β2‐adrenoceptor gene is associated with increased body weight and dyslipoproteinaemia involving triglyceride‐rich lipoproteins. J Intern Med 2000; 247: 651–656.

Objectives. To investigate whether a substitution of glutamine by glutamic acid at amino acid position 27 (Q/E27) and an arginine to glycine transition at amino acid 16 (R/G16) in the β2‐adrenoceptor gene are associated with lipid and lipoprotein disturbances and/or increased body weight in men.

Design. Population‐based study.

Setting. Department of medicine at a university hospital.

Subjects. A total of 180 healthy men, aged 30–45 years, were recruited at random from a register containing all permanent residents in Stockholm County (response rate of 70%).

Main outcome measures. Frequency of β2‐adrenoceptor genotypes and alleles in relation to plasma lipid and lipoprotein levels and body mass index.

Results. Individuals carrying the E27 allele and/or the G16 allele had significantly higher body mass index (BMI). Furthermore, carriers of the E27 allele had significantly higher plasma concentrations of cholesterol, triglycerides, VLDL cholesterol and VLDL triglycerides than did subjects homozygous for the Q allele.

Conclusion. The E27 allele of the β2‐adrenoceptor gene is associated with slightly to moderately elevated BMI and dyslipoproteinaemia involving triglyceride‐rich lipoproteins in healthy younger and middle‐aged men.
Short stature and coronary heart disease: a 35‐year follow‐up of the Finnish cohorts of The Seven Countries Study
Authors: Forsén T. , Eriksson J. , Qiao Q. , Tervahauta M. , Nissinen A. , Tuomilehto J.
Published: March 2003

Abstract. Forsén T, Eriksson J, Qiao Q, Tervahauta M, Nissinen A, Tuomilehto J (National Public Health Institute, Helsinki, and University of Kuopio, Kuopio, Finland). Short stature and coronary heart disease: a 35‐year follow‐up of the Finnish cohorts of The Seven Countries Study. J Intern Med 2000; 248: 326–332.

Objectives. To examine whether short stature is associated with an increased risk of coronary heart disease.

Design. Follow‐up study.

Setting. Two geographically defined areas in eastern and western Finland.

Subjects. A total of 1441 men who were free of coronary heart disease at the start of the follow‐up.

Main outcome measures. Hazard ratios for fatal and non‐fatal coronary heart disease

Results. Height was inversely related to fatal coronary heart disease and incident non‐fatal coronary heart disease during the follow‐up. These relationships persisted after adjusting for other major cardiovascular risk factors. Comparing the high‐risk area in eastern Finland with the low‐risk area in south‐western Finland, no difference in fatal coronary heart disease and cumulative incidence of non‐fatal coronary heart disease was seen in tall men. The increase in risk of coronary heart disease death was 19% for a 10 cm decrease in height (OR = 0.81, 95% CI = 0.68–0.95).

Conclusions. Our results show that short stature is an independent risk factor for coronary heart disease. Differences in stature partly explain the Finnish east–west difference in the incidence of coronary heart disease.
Identification of a new coeliac disease subgroup: antiendomysial and anti‐transglutaminase antibodies of IgG class in the absence of selective IgA deficiency
Authors: Picarelli A. , Di Tola M. , Sabbatella L. , Mastracchio A. , Trecca A. , Gabrielli F. , Di Cello T. , Anania M. C. , Torsoli A.
Published: March 2003

Abstract. Picarelli A, Di Tola M, Sabbatella L, Mastracchio A, Trecca A, Gabrielli F, Di Cello T, Anania MC, Torsoli A (University of Rome “La Sapienza”, Rome, Italy). Identification of a new coeliac disease subgroup: antiendomysial and anti‐transglutaminase antibodies of IgG class in the absence of selective IgA deficiency.J Intern Med2001;249:181–188.

Objective. The aim of the present study was to increase the sensitivity of the antiendomysial antibody (EMA) test by evaluating also EMAs of IgG1 isotype.

Design and subjects. Over the last 2 years, serum EMAs IgA and IgG1 were determined in 1399 patients, referred to our gastrointestinal unit due to clinical suspicion of malabsorption. Serum anti‐tissue transglutaminase (tTG) antibodies IgA and IgG, as well as total IgA levels, were also investigated. Furthermore, EMAs IgA and IgG1 were evaluated in biopsy culture supernatants. Biopsy specimens were also admitted to histological and immunohistochemical evaluation. Twenty‐six patients with gastroenterological disease other than coeliac disease (CD) were used as a disease control group. Ninety‐nine blood donors were used as a healthy control group.

Results. Diagnosis of CD was based on histological findings in the 110/1399 patients showing EMA IgA positivity, and in a further 56/1399 patients presenting both EMA IgA and IgG1 positivity in sera as well as in culture supernatants. Of the remaining 1233 EMA IgA‐negative patients, 60 showed only EMA IgG1 positivity both in sera and in culture supernatants. It is noteworthy that anti‐tissue transglutaminase antibodies IgG (anti‐tTG) were positive in all 60 EMA IgG1‐positive patients as well. By contrast, a selective IgA deficiency was found in only 11 out of the 60 EMA IgG1‐positive patients. Villous height/crypt depth ratio was < 3:1 in 38 of the 60 EMA IgG1‐positive patients (63.3%), whilst overexpression of ICAM‐1 and CD25 was observed in all these patients.

Conclusions. In this study, we observed a group of CD patients who were EMA IgG1‐positive even in the absence of EMA IgA positivity and IgA deficiency. The diagnosis was based on the finding of the gluten‐dependent clinical and histological features typical of CD. Data emerging from the present investigation thus suggest that the prevalence of CD should be reassessed and that the determination of EMA IgG1 could offer a new tool in the diagnostic armamentarium of CD.
Comparison of echocardiography and radionuclide ventriculography in the follow‐up of left ventricular systolic function in adult lymphoma patients during doxorubicin therapy
Authors: Nousiainen T. , Vanninen E. , Jantunen E. , Puustinen J. , Remes J. , Rantala A. , Hartikainen J.
Published: March 2003

Abstract. Nousiainen T, Vanninen E, Jantunen E, Puustinen J, Remes J, Rantala A, Hartikainen J (Kuopio University Hospital; Satakunta Central Hospital, Pori; Finland). Comparison of echocardiography and radionuclide ventriculography in the follow‐up of left ventricular systolic function in adult lymphoma patients during doxorubicin therapy (Original Article). J Intern Med 2001; 249: 297–303.

Objectives. To compare echocardiography (ECHO) and radionuclide ventriculography (RVG) in the monitoring of left ventricular systolic function during doxorubicin therapy in adult lymphoma patients.

Design. Prospective study.

Settings. University hospital.

Subjects. A total of 28 adult patients who received doxorubicin to a cumulative dose of 400–500 mg m–2.

Main outcome measures. ECHO and RVG were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m–2.

Results. At baseline, the mean (±SE) left ventricular ejection fractions (LVEF) were 58 ± 1.3, 71 ± 1.8 and 58 ± 1.7% as determined by RVG, M‐mode ECHO and two‐dimensional (2D) ECHO, respectively. After the cumulative doxorubicin dose of 500 mg m–2 LVEF decreased to 49.6 ± 1.7% (RVG) (P < 0.001), 62 ± 1.6% (M‐mode) (P=0.006) and 52.5 ± 1.3% (2D ECHO) (P=0.036). Although a significant correlation between LVEF determined by RVG and M‐mode ECHO (r=0.615, P=0.002) and a trend between RVG and 2D ECHO (r=0.364, P=0.096) were observed, there were substantial differences in the results of individual patients. In the agreement analysis using the method of Bland and Altman there was a mean difference of 12% units with the upper limit of agreement +26% units and the lower limit of agreement –2.1% units for LVEF determinations with M‐mode ECHO and RVG, and a mean difference of 3.3% units with upper and lower limits of agreement +19.6 and –13.1% units for LVEF determinations with 2D ECHO and RVG, respectively.

Conclusion. We found only a moderate agreement between left ventricular systolic function determined by ECHO and RVG methods. Thus, in the follow‐up of left ventricular function in adult patients during doxorubicin therapy, the guidelines based on LVEF measurement by RVG cannot be applied to ECHO. Consequently, RVG remains the method of choice in this context.
A high prevalence of hypovitaminosis D in Finnish medical in‐ and outpatients
Authors: Kauppinen‐Mäkelin R. , Tähtelä R. , Löyttyniemi E. , Kärkkäinen J. , Välimäki M. J.
Published: March 2003

Abstract. Kauppinen‐Mäkelin R, Tähtelä R, Löyttyniemi E, Kärkkäinen J, Välimäki MJ (Peijas Hospital, Vantaa; United Laboratories, Leiras Research, and Division of Endocrinology; Helsinki University Central Hospital, Helsinki, Finland). A high prevalence of hypovitaminosis D in Finnish medical in‐ and outpatients. J Intern Med 2001; 249: 559–563.

Objective. To study the prevalence of hypovitaminosis D [serum 25(OH)D ≤ 37 nmol L−1)] in Finnish medical in‐ and outpatients in a cross‐sectional study.

Methods. The subjects were 106 consecutive medical inpatients (57 females, 49 males with mean ages of 65 and 58 years) from the Peijas Hospital, Vantaa, Finland, and 99 ambulatory patients (48 females, 51 males with mean ages of 42 and 46 years) contacting a private outpatient centre in Helsinki, Finland. Serum 25(OH)D, vitamin D binding protein (DBP), free vitamin D index (FDI), intact PTH (iPTH), and albumin‐corrected calcium were measured.

Results. Serum 25‐hydroxyvitamin D [25(OH)D] was 37 nmol L−1 or less in 70% of female and in 61% of male inpatients and in 44% of female and in 37% of male outpatients. In the whole population, a statistically significant inverse association (P < 0.0001) was detected between iPTH and 25(OH)D levels; the iPTH concentration appeared to start increasing when 25(OH)D concentration was 50 nmol L−1 or less. The association remained the same (P < 0.0001) when FDI was used instead of 25(OH)D in the calculations. When the sexes were analysed separately, the statistically significant association was found only in females (P < 0.0001 for iPTH versus 25(OH)D; P < 0.0001 for iPTH versus FDI) but not in males.

Conclusion. Hypovitaminosis D is very common amongst Finnish in‐ and outpatients in both sexes, causing secondary hyperparathyroidism in females. More extensive studies are warranted to elucidate the vitamin D status of the Finnish population.
Use of dietary supplements and natural remedies increased dramatically during the 1990s
Authors: Messerer M. , Johansson S.‐E. , Wolk A.
Published: March 2003

Abstract. Messerer M, Johansson S‐E, Wolk A (Karolinska Institutet and Statistics Sweden, Stockholm, Sweden). Use of dietary supplements and natural remedies increased dramatically during the 1990s. J Intern Med 2001; 250: 160–166.

Objectives. To estimate the prevalence and trends in dietary supplement and natural remedy use in Sweden during the 1980s and 1990s.

Design. Three nationally representative, cross‐sectional surveys conducted in 1980–81, 1988–89 and 1996–97 were used for analysis. In face‐to‐face interviews participants reported consumption of dietary supplements and natural remedies during the previous 2 weeks.

Setting. Sweden.

Subjects. The samples consisted totally of 38 594 adults aged 16–84 years (14 642 in the 1980–81 survey, 12 391 in the 1988–89 survey and 11 561 in the 1996–97 survey).

Main outcome measures. Changes in prevalence of dietary supplement and natural remedy users between 1980 and 1997.

Results. The 70% increase in the prevalence of dietary supplement users amongst both men and women [odds ratio (OR), 1.7; 95% confidence interval (CI), 1.6–1.9, OR, 1.7; 95% CI, 1.5–1.8, respectively] occurred mainly between 1988–89 and 1996–97. The increase in the prevalence of natural remedy users was even more dramatic – more than threefold in men (OR, 3.3; 95% CI, 2.9–4.0) and almost threefold in women (OR, 2.6; 95% CI, 2.3–2.9) – and the systematic increase started already in the 1980s. The increase was observed in all age groups and in all socio‐economic groups, except for farmers. In 1996–97 the prevalence of dietary supplement users was 22% amongst men and 33% amongst women, and of natural remedies 7 and 14%, respectively.

Conclusions. During the last two decades, the use of dietary supplements and natural remedies amongst the adult Swedish population has dramatically increased.
Screening for thyroid disease of 15–17‐year‐old schoolchildren in an area with normal iodine intake
Authors: Milakovic M. , Berg G. , Eggertsen R. , Lindstedt G. , Nyström E.
Published: March 2003

Abstract. Milakovic M, Berg G, Eggersten R, Lindstedt G, Nyström E (Sahlgrenska University Hospital, Göteborg, Sweden). Screening for thyroid disease of 15–17‐year‐old schoolchildren in an area with normal iodine intake. J Intern Med 2001; 250: 208–212.

Objective. The prevalence of thyroid disease in Swedish schoolchildren is today insufficiently known. The aim of the study was therefore to determine the prevalence of abnormal thyroid function and thyroid autoimmunity in teen‐age schoolchildren and to compare the findings with a healthy control group of 60–65‐year‐old inhabitants from the same community.

Setting. A semirural community of approximately 15 000 inhabitants.

Design. Cross‐sectional study.

Main outcome measures. Thyroid volume and serum concentrations of serum thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3′‐triiodothyronine (T3), and antithyroperoxidase antibodies (TPOAb).

Results. Four schoolchildren (7%, 59 screened) had elevated TPOAb concentration, three of the subjects being girls (8%). One girl with a goitre was overtly hypothyroid and one girl showed borderline‐high serum TSH concentration suggesting subclinical autoimmune thyroid disease. One euthyroid boy had a goitre and high concentration of TPOAb. The serum free T3 concentration was significantly higher in 15–17‐year‐old than 60–65‐year‐old (7.4 vs. 6.4 pmol L–1, P < 0.001). The concentrations of other thyroid hormones and of TSH in 15–17‐year‐old did not differ from those of the 60–65‐year‐old.

Conclusions. We found three cases of thyroid disease in need of immediate attention or later follow‐up. The prevalence of autoimmune thyroid disease was high as indicated from TPOAb measurements. Thyroid tests including TPOAb measurement should be performed on wide indications when teenagers seek medical advice. The reference intervals for teen‐age children for commonly used first line tests (TSH and free T4) do not differ from those for adults.
Value of structured clinical and scintigraphic protocols in acute pulmonary embolism
Authors: Nilsson T. , Måre K. , Carlsson A.
Published: March 2003

Abstract. Nilsson T, Måre K, Carlsson A (Karolinska Hospital, Linköping University Hospital; and Danderyd Hospital, Sweden). Value of structured clinical and scintigraphic protocols in acute pulmonary embolism. J Intern Med 2001; 250: 213–218.

Purpose. To study the use of a combination of a clinical and scintigraphic protocol in relation to the final outcome diagnosis in patients with clinical suspicion of acute pulmonary embolism (PE).

Material and methods. A total of 170 patients with clinical suspicion of acute PE were all examined with ECG, blood chemistry, chest X‐ray, pulmonary scintigraphy and selective pulmonary arteriography. The scintigraphic and clinical probabilities of PE were estimated on visual analogue scales (VASs) by different readers unaware of each others’ results. The follow‐up time was 6 months. In order to establish the final diagnosis a final outcome committee was created. They analysed in retrospect all the clinical and laboratory data and established whether the patient had had PE or not.

Results. The final outcome committee concluded that 53 patients had PE. When the scintigraphic and clinical probability judgements were congruent, a combined probability of 1–25% (i.e low probability) had a negative predictive value of 98%. When the combined probability was 26–75% (i.e. intermediate) half of the cases had PE. With a combined probability of 76–100% (i.e. high) the positive predictive value was 100%.

Conclusion. By applying a model of combined clinical and scintigraphic probabilities for PE, the diagnosis is ruled in when the combined probability is high, and ruled out when the combined probability is low. However, nearly half of the patients will still have an uncertain diagnosis for which further diagnostic procedures may be allocated.
A definition‐based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome
Authors: De Becker P. , McGregor N. , De Meirleir K.
Published: March 2003

Abstract. De Becker P, MCGregor N, De Meirleir K (VUB, Vakgroep Interne Geneeskunde, Brussels, Belgium; and University of Newcastle, Callaghan, New South Wales, Australia). A definition‐based analysis of symptoms in a large cohort of patients with chronic fatigue syndrome. J Intern Med 2001; 250: 234–240.

Objective. The Holmes and Fukuda criteria are widely used criteria all over the world, yet a specific European study regarding chronic fatigue syndrome (CFS) patient symptomatology has not been conducted so far. This study was performed to answer the need to assess the homogeneity of a large CFS population in relationship to the Fukuda or Holmes definitions and to assess the importance of a symptom severity scale.

Design. Multivariate analyses were performed to assess the symptom presentation within a fatigued population and the differences between the Fukuda and Holmes definitions compared with an excluded chronic fatigued group in a large cohort of fatigued patients.

Setting. An outpatient tertiary care setting fatigue clinic in Brussels.

Main outcome measures. Prevalence and severity of symptoms and signs in a CFS population and in a chronic fatigued population.

Subjects and methods. A total of 2073 consecutive patients with major complaints of prolonged fatigue participated in this study. Multivariate analyses were performed to assess the symptom presentation and severity and the differences between the Fukuda and Holmes definitions.

Results. Of the 2073 patients complaining of chronic fatigue (CF), 1578 CFS patients fulfilled the Fukuda criteria (100% of CFS group) and 951 (60.3% of the CFS group) fulfilled the Holmes criteria. Discriminant function analysis revealed that the Fukuda and Holmes definitions can be differentiated by symptom severity and prevalence. The Holmes definition was more strongly associated than the Fukuda definition with the symptoms that differentiated the CFS patients from the patients that did not comply with the CFS definitions. The inclusion of 10 additional symptoms was found to improve the sensitivity/specificity and accuracy for selection of CFS patients.

Conclusions. The CFS patients fulfilling the Holmes criteria have an increased symptom prevalence and severity of many symptoms. Patients fulfilling the Fukuda criteria were less severely affected patients which leads to an increase in clinical heterogeneity. Addition of certain symptoms and removal of others would strengthen the ability to select CFS patients.
Prediction of five‐year survival for patients admitted to a department of internal medicine
Authors: Eriksen B. O. , Kristiansen I. S. , Pape J. FR.
Published: March 2003

Abstract. Eriksen BO, Kristiansen IS, Pape JFr (University Hospital of Tromsø and University of Tromsø, Tromsø, Norway). Prediction of five‐year survival for patients admitted to a department of internal medicine. J Intern Med 2001; 250: 435–440.

Objective. The effect of many common forms of therapy, as medication for mild hypertension or hypercholesterolaemia, only reaches clinical significance after years of treatment. The meaningful application of such therapy presupposes that physicians can, at least to some extent, predict the remaining lifetime of patients. We investigated whether clinicians from different disciplines were able to predict the 5‐year survival of patients admitted to a department of internal medicine.

Design. The members of two groups, each consisting of an internist, a surgeon and a general practitioner, made individual predictions of the expected remaining lifetime of discharged patients from written summaries of clinical information. Each patient was randomized to be assessed by the members of either of the two groups. The predictions were compared with actual 5‐year survival.

Setting. Department of internal medicine at a university hospital.

Subjects. Patients admitted consecutively during a 6‐week period.

Main outcome measures. Sensitivity, specificity, positive and negative predictive values and areas under the receiver operating characteristic (ROC) curves for predictions of 5‐y ear survival for each of the six experts.

Results. A total of 402 patients were included. Five‐year survival was 0.63. The sensitivity of the predictions ranged from 0.81 to 0.95, the specificity from 0.61 to 0.77, the positive predictive value from 0.78 to 0.87 and the negative predictive value from 0.68 to 0.87. The areas under the ROC curves ranged from 0.84 to 0.91.

Conclusion. The quality of predictions of 5‐year survival made by experienced clinicians should permit the rational use of treatments with long‐term effects.