bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and characterization of the multiple endocrine neoplasia type 1 (MEN1) gene
Authors: Guru  , Manickam  , Crabtree  , Olufemi  , Agarwal  , Debelenko  , Zhuang  , Lubensky  , Kester  , Kim  , Heppner  , Weisemann  , Boguski  , Wang  , Roe  , Burns  , Liotta  , Spiegel  , Emmert‐Buck  , Marx  , Collins  , Chandrasekharappa  
Published: March 2003

Guru SC, Manickam, Crabtree JS, Olufemi S‐E, Agarwal SK, Debelenko LV, Zhuang Z, Lubensky IA, Kester MB, Kim YS, Heppner C, Weisemann JM, Boguski MS, Wang Y, Roe BA, Burns AL, Liotta LA, Speigel AM, Emmert‐Buck MR, Marx SJ, Collins FS, Chandrasekharappa SC (National Institutes of Health, Bethesda; University of Oklahoma, Norman; USA). Identification and characterization of the multiple endocrine neoplasia type 1 (MEN1) gene (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 433–9.For nearly a decade since the mapping of the multiple endocrine neoplasia type 1 (MEN1) locus to 11q13 and the suggestion that it is a tumour suppressor gene, efforts have been made to identify the gene responsible for this familial cancer syndrome. Recently, we have identified the MEN1 gene by the positional cloning approach. This effort involved construction of a 2.8‐Mb physical map (D11S480–D11S913) based primarily on a bacterial clone contig. Using these resources, 20 new polymorphic markers were isolated which helped to reduce the interval for candidate genes by haplotype analysis in families and by loss of heterozygosity (LOH) studies in approximately 200 tumours, utilizing laser‐assisted microdissection to obtain tumour cells with minimal or no admixture by normal cells. The interval was narrowed by LOH to only 300 kb, and nearly 20 new transcripts that map to this region of 11q13 were isolated and characterized. One of the transcripts was found by dideoxyfingerprinting and cycle sequencing to harbour deleterious germline mutations in affected individuals from MEN‐1 kindreds and therefore identified as the MEN1 gene. The type of germline mutations and the identification of mutations in sporadic tumours support the Knudson's two‐hit model of tumorigenesis for MEN‐1. Efforts are being made to identify the function of the MEN1 gene‐encoded protein, menin, and to study its role in tumorigenesis.
Effects of atorvastatin on serum lipids of patients with familial hypercholesterolaemia
Authors: Hoogerbrugge  
Published: March 2003

Hoogerbrugge N (University Hospital Dijkzigt, Rotterdam, the Netherlands). Effects of atorvastatin on serum lipids of patients with familial hypercholesterolaemia. J Intern Med 1998; 244: 143–7.ObjectivesThe effects of atorvastatin, a new synthetic HMG‐CoA reductase inhibitor, were investigated in patients with familial hypercholesterolaemia (FH), with high LDLc levels whilst on standard treatment.DesignOpen treatment with 40 mg atorvastatin daily for 6 weeks, followed by another 6 weeks with 80 mg atorvastatin.SettingOutpatient lipid clinic of a tertiary referral centre.SubjectsFH was diagnosed when the untreated LDLc concentration was higher than 6 mmol L−1, tendon xanthomas were present at the participant or a first degree relative, and the family history for hypercholesterolaemia was positive. The FH patients were selected for an LDLc above 5.0 mmol L−1 whilst on standard therapy for at least 3 months. Standard therapy consisted of a diet and 40 mg simvastatin, either alone (n= 17), or in combination with 8–12 g colestyramin (n= 12), or 1800 mg nicotinic acid (n= 12).Main outcome measureEffects on LDLc concentration.ResultsLDLc concentration significantly decreased during treatment with 80 mg atorvastatin as compared to LDLc levels on 40 mg simvastatin alone or in combination with 8–12 g colestyramin, by 24 ± 14% (P < 0.01) and 19 ± 22% (P < 0.01), respectively. LDLc concentration was comparable during treatment with 80 mg atorvastatin or 40 mg simvastatin in combination with 1800 mg nicotinic acid. Atorvastatin was tolerated well, no side‐effects were observed.ConclusionsAtorvastatin is a valuable addition to the treatment possibilities of patients with serious hypercholesterolaemia, like FH.
The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection
Authors: Leibovici  , Shraga  , Drucker  , Konigsberger  , Samra  , Pitlik  , Pitlik  
Published: March 2003

Abstract. Leibovici L, Shraga I, Drucker M, Konigsberger H, Samra Z, Pitlik SD (Rabin Medical Center, Petah‐Tiqva, and Tel‐Aviv University, Tel‐Aviv, Israel). The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998; 244: 379–86.ObjectivesTo test whether empirical antibiotic treatment that matches the in vitro susceptibility of the pathogen (appropriate treatment) improves survival in patients with bloodstream infections; and to measure the improvement.DesignObservational, prospective cohort study.SettingUniversity hospital in Israel.SubjectsAll patients with bloodstream infections detected during 1988–94.InterventionsNone.Main outcome measuresIn‐hospital fatality rate and length of hospitalization.ResultsOut of 2158 patients given appropriate empirical antibiotic treatment, 436 (20%) died, compared with 432 of 1255 patients (34%) given inappropriate treatment (P = 0.0001). The median durations of hospital stay for patients who survived were 9 days for patients given appropriate treatment and 11 days for patients given inappropriate treatment. For patients who died, the median durations were 5 and 4 days, respectively (P < 0.05), for both comparisons.In a stratified analysis, fatality was higher in patients given inappropriate treatment than in those given appropriate treatment in all strata but two: patients with infections caused by streptococci other than Streptococcus gr. A and Streptoccocus pneumoniae (odds ratio (OR) of 1.0, 95% confidence interval (95% CI) 0.4–2.5); and hypothermic patients (OR = 0.9, 95% CI = 0.3–2.4). Even in patients with septic shock, inappropriate empirical treatment was associated with higher fatality rate (OR = 1.6, 95% CI = 1.0–2.7). The highest benefit associated with appropriate treatment was observed in paediatric patients (OR = 5.1, 95% CI = 2.4– 10.7); intra‐abdominal infections (OR = 3.8, 95% CI = 2.0–7.1); infections of the skin and soft tissues (OR = 3.1, 95% CI = 1.8–5.6); and infections caused by Klebsiella pneumoniae (OR = 3.0, 95% CI = 1.7–5.1) and S. pneumoniae (OR = 2.6, 95% C = 1.1–5.9).On a multivariable logistic regression analysis, the contribution of inappropriate empirical treatment to fatality was independent of other risk factors (multivariable adjusted OR = 1.6, 95% CI = 1.3–1.9).ConclusionAppropriate empirical antibiotic treatment was associated with a significant reduction in fatality in patients with bloodstream infection.
Atorvastatin compared with simvastatin in patients with severe LDL hypercholesterolaemia treated by regular LDL apheresis
Authors: Geiss H. C. , Parhofer K. G. , Schwandt P. 
Published: March 2003

Abstract.Objectives. Atorvastatin is a new potent HMG‐CoA reductase inhibitor. We evaluated whether patients with coronary heart disease and severe hypercholesterolaemia showing insufficient LDL (low‐density lipoprotein) cholesterol reduction despite combined therapy with simvastatin and regular LDL apheresis will benefit from atorvastatin therapy.Setting. Tertiary care centre, university hospital.Methods. In 21 patients treated by LDL apheresis, concomitant simvastatin therapy (40 mg day−1) was replaced by atorvastatin (40 mg day−1) and increased to 60 and 80 mg day−1 (each for 3 months) if no side‐effects were reported and NCEP treatment goals were not reached.Results. In 20 of 21 patients (95%), atorvastatin resulted in significant reduction of LDL cholesterol compared with simvastatin (by 10%, additional 8% and additional 1%, with 40, 60 and 80 mg day−1, respectively). In four patients, NCEP treatment goals were reached (in three by atorvastatin alone, and in one by atorvastatin and apheresis). Patients with little reduction in LDL cholesterol to 40 mg day−1 atorvastatin benefited most by increasing the dose to 60 mg day−1 (additional 13% reduction), whilst those responding to atorvastatin 40 mg day−1 benefited less (additional 1.9% reduction). During atorvastatin therapy, significantly less plasma had to be treated during apheresis resulting in shorter apheresis time. Eight patients (38%) reported side‐effects, resulting in discontinuation of atorvastatin in three (14%) and dose reduction in five patients (24%), whilst no elevation of biochemical markers was observed.Conclusion. Concomitant atorvastatin therapy is superior to simvastatin therapy in patients with severe hypercholesterolaemia treated with regular LDL apheresis, but is associated with a high rate of subjective side‐effects.
Pulmonary embolism: a follow‐up study of the relation between the degree of right ventricle overload and the extent of perfusion defects
Authors: Ribeiro A. , Lindmarker P. , Johnsson H. , Juhlin‐Dannfelt A. , Jorfeldt L. 
Published: March 2003

Abstract.Ribeiro A, Lindmarker P, Johnsson H, Juhlin‐Dannfelt A, Jorfeldt L (Karolinska Hospital, Karolinska Institute, Stockholm, Sweden).Pulmonary embolism: a follow‐up study of the relation between the degree of right ventricle overload and the extent of perfusion defects.J Intern Med1999;245: 601–610.Objectives.To describe the course of changes in perfusion lung scintigraphy (LS) after acute pulmonary embolism (PE) and test the hypothesis that patients with persistent pulmonary hypertension (PH)/right ventricle (RV) dysfunction after acute PE can be differentiated from those without through larger perfusion defects (PDf) on LS.Design.Prospective, one‐year follow‐up study with repeated LS and echocardiography‐Doppler investigations.Setting.Single centre, University Hospital.Subjects.Patients with clinical suspicion of acute PE with a diagnosis confirmed by LS and/or pulmonary angiography and able to undergo repeated investigations. Of the 78 patients included, a six‐week follow‐up was completed in 67 and a one‐year follow‐up in 64.Main outcome measures.Time course of PDf in relation to time course of pulmonary artery systolic pressure (PAsP) and RV function.Results.Initially, PDf decreased exponentially, until the beginning of a stable phase, which was achieved within 54 days for 90% of the patients and within 148 days for all. The temporal relation for the regress of PDf and decrease in PAsP was loose. Patients with persistent PDf suffered PH/RV dysfunction more often than those without. However, the variability in the degree of haemodynamic changes for a given extent of PDf was large.Conclusions.After acute PE, LS is of use for the identification of the group of patients that may have persistent PH/RV dysfunction. However, since the identification of individual patients is uncertain, LS cannot replace echocardiography‐Doppler in the identification of persistent PH/RV dysfunction after acute PE.
Effects of nicotine nasal spray on atherogenic and thrombogenic factors during smoking cessation
Authors: Lúdvíksdóttir D. , Blöndal T. , Franzon M. , Gudmundsson T. V. , Säwe U. 
Published: March 2003

Objectives. To investigate changes in cardiovascular risk factor parameters when stopping smoking and to identify any impact of nicotine nasal spray on these factors.Design and subjects. In a placebo‐controlled, double‐blind 3‐month prospective study, nicotine nasal spray (NNS) or a placebo was given to 157 subjects attending a smoking cessation programme. Blood samples from 46 subjects who remained abstinent for 3 months were analysed. Nasal spray use was given on an ad libitum basis.Results. The haemoglobin (Hb) decreased from 149.0 to 143.2 g L–1 (P < 0.001). The haematocrit (Hct) decreased from 44.6 to 42.4% (P < 0.001). The mean corpuscular volume (MCV) decreased from 93.4 to 92.3 fl (P < 0.001). The mean corpuscular haemoglobin concentration (MCHC) increased from 333.9 to 338.1 g L–1 (P = 0.029). The white blood cell count (WBC) decreased from 8.4 to 6.6 × 109 L–1 (P < 0.001). The total cholesterol decreased from 5.92 to 5.65 mmol L–1 (P = 0.015). The high‐density lipoprotein cholesterol (HDL) increased from 1.29 to 1.44 mmol L–1 (P = 0.48) and low‐density lipoprotein cholesterol (LDL) decreased from 4.00 to 3.54 mmol L–1 (P = 0.004). The HDL/LDL ratio increased from 0.36 to 0.46 (P = 0.011).Conclusion. Stopping smoking resulted in positive effects on cardiovascular risk factors. Nicotine treatment for as long as 3 months did not have any significant effect on these ‘stopping smoking changes’. In smoking cessation, nicotine substitution up to 3 months seems to be safe.
Oestrogen receptors – an overview
Authors: Enmark E. , Gustafsson J.‐Å. 
Published: March 2003

Enmark E, Gustafsson J‐A (Karolinska Institutet, Huddinge, Sweden). Oestrogen receptors – an overview (Review). J Intern Med 1999; 246: 133–138.The oestrogen receptor (ER) is a ligand‐activated transcription factor that mediates the effects of the steroid hormone 17β‐oestradiol in both males and females. Since the isolation and cloning of ER, the prevailing opinion has been that only one such receptor exists. The finding of a second subtype of ER (ERβ) has caused considerable excitement and has forced endocrinologists to re‐evaluate many aspects of the actions of oestrogens. In this article, we will try to summarize the current knowledge about the two oestrogen receptor subtypes, with the emphasis on oestrogen receptor β (ERβ), and to comment on the observations in mice lacking either receptor or the hormone itself.
Heart rate and mortality
Authors: Reunanen A. , Karjalainen J. , Ristola P. , Heliövaara M. , Knekt P. , Aromaa A. 
Published: March 2003

Abstract.Reunanen A, Karjalainen J, Ristola P, Heliövaara M, Knekt P, Aromaa A (National Public Health Institute, Helsinki, Central Military Hospital, Helsinki, and Kvaerner Masa‐Yards Helsinki New Shipyard, Helsinki, Finland). Heart rate and mortality.J Intern Med2000;247: 231–239.Objectives.Increased heart rate has shown to be associated with risk of mortality from cardiovascular diseases in some studies, but not in others. Increased heart rate has also been linked to causes of death other than cardiovascular. To clarify the role of heart rate as a predictor of death we studied its predictive value in a large population study.Design.A prospective population study with a follow‐up time of 23 years.Subjects and methods.The study population comprised 5598 men and 5119 women 30–59 years of age on entry. Heart rate was measured from resting ECGs.Main outcome measure.Mortality from specified causes.Results.A total of 1848 men and 840 women died during the follow‐up period. Increased heart rate was significantly associated with death from all causes, cardiovascular causes, and natural noncardiovascular, nonmalignant causes of death. Increased heart rate was associated with death from cancer in men with heart disease but not in men without heart disease on entry into the study. The increase in cardiovascular mortality with high heart rate was explained by the close association between heart rate and blood pressure. Adjustment for risk factors did not alter the significance of the association between increased heart rate and mortality from noncardiovascular causes.Conclusions.High heart rate is simple to observe clinically and a significant if nonspecific predictor of mortality. Increased risk of mortality from cardiovascular diseases can be explained by association with high blood pressure. The increased mortality risk associated with high heart rate related mainly to a group of diseases of noncardiovascular or nonmalignant origin.
Adverse endothelial function and the insulin resistance syndrome
Authors: Tooke J. E. , Hannemann M. M. 
Published: March 2003

Abstract. Tooke JE, Hannemann MM (School of Postgraduate Medicine and Vascular Health Sciences, University of Exeter, Devon). Adverse endothelial function and the insulin resistance syndrome (Review). J Intern Med 2000; 247: 425–431.Type 2 diabetes is characterized by impaired endothelial dependent vasodilatation which may contribute to the high prevalence of vascular disease in such patients. Although hyperglycaemia, dyslipidaemia and hypertension can all independently cause a similar defect, recent data suggest that endothelial dysfunction may be intrinsic to the insulin resistance syndrome that commonly precedes type 2 diabetes. Such abnormalities in endothelial function could represent the impact of subclinical disturbance of metabolism or alternatively the presence of a common cellular defect that influences both nitric oxide bioavailability and insulin mediated glucose disposal. Resolution of this puzzle is likely to lead to important advances in our knowledge and ultimately treatment of vascular disease.
Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements
Authors: Van Soolingen D. 
Published: March 2003

Abstract. van Soolingen D (National Institute of Public Health and the Environment, Bilthoven, The Netherlands). Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements (Review). J Intern Med 2001; 249: 1–26.In the last decade, DNA fingerprint techniques have become available to study the interperson transmission of tuberculosis and other mycobacterial infections. These methods have facilitated epidemiological studies at a population level. In addition, the species identification of rarely encountered mycobacteria has improved significantly. This article describes the state of the art of the main molecular typing methods for Mycobacterium tuberculosis complex and non‐M. tuberculosis complex (atypical) mycobacteria. Important new insights that have been gained through molecular techniques into epidemiological aspects and diagnosis of mycobacterial diseases are highlighted.
The effect of 24 h blood pressure levels on early neurological recovery after stroke
Authors: Bhalla A. , Wolfe C.D.A , Rudd A.G. 
Published: March 2003

Abstract. Bhalla A, Wolfe CDA, Rudd AG (Guy’s, King’s and St Thomas’ Hospital, London) J Intern Med 2001; 250: 121–130. Objectives. To assess the influence of 24 h blood pressure (BP) levels on functional recovery 1 week after stroke and the effect of antihypertensive therapy on 24 h BP levels. Design. Prospective study of patients admitted to hospital over 1 year with first in a lifetime stroke who underwent 24 h BP and casual measurements. Setting. Medical wards in a teaching hospital. Subjects. Of 160 patients, 72 patients admitted to hospital within 24 h of stroke onset were investigated. Patients with conditions and therapy that interfered with autonomic and sympathetic function were excluded. Interventions. All subjects underwent 24 h BP and casual recordings on admission to hospital and at day seven after stroke. The mean 24 h, day and night systolic BP (SBP) and diastolic BP (DBP) and their differences (nocturnal BP dip) were recorded. Patients were divided into three groups according to whether they were taking antihypertensive therapy during the first week: (i) no therapy, (ii) therapy continued after stroke, and (iii) new therapy introduced. Main outcome measures. Functional recovery (Rankin Scale 0–1) and neurological improvement [Scandinavian Stroke Scale (SSS) ≥3 points] by 1 week of stroke. Change in circadian 24 h BP over 1 week. Results. For each 10 mmHg difference between day and night time DBP, the odds for making a complete recovery were 4.63 (95% CI: 1.57–13.7, P=0.01). For each 10 mmHg difference between day and night SBP, the odds for making an improvement in neurological status was 2.24 (95% CI: 1.16–4.32; P=0.016). Significant falls in 24 h DBP (P=0.01), daytime SBP (P=0.005) and mean arterial BP (MABP) (P=0.04) over 1 week were demonstrated in patients who had just commenced antihypertensive therapy (P=0.001). Conclusion. An increase in day to night time BP change is favourable in short‐term outcome after acute stroke. Significant falls in BP are more likely in patients started on antihypertensive therapy for the first time. Further research is required to understand the effects of circadian BP rhythm on stroke outcome.
Chemokines in pathology and medicine
Authors: Baggiolini M. 
Published: March 2003

Abstract. Baggiolini M (Theodor Kocher Institute, University of Bern, and Institute for Research in Biomedicine, Bellinzona, Switzerland). Chemokines in pathology and medicine (Review). J Intern Med 2001; 250: 91–104.About 50 human chemokines and nearly 20 receptors have been identified and characterized in little more than a decade since the discovery of interleukin 8 (IL‐8), the first chemotactic cytokine. Research in this field has dramatically changed our understanding of leucocyte traffic in inflammation and immunity. This paper has been written for scientists and practitioners in the field of medicine. It reviews in concise and intelligible form information that I consider useful for understanding the role of chemokines in human pathophysiology. The main areas covered are: (i) the basics of chemokine structures, mode of action, activities and selectivity; (ii) newer aspects of the broad involvement of chemokines in the regulation of immune defence and the housekeeping of the immune system; (iii) the role of chemokines in pathology as illustrated by animal models and studies of human diseases; and (iv) novel therapeutic approaches for a variety of inflammatory conditions, which are based on modulation of chemokine activity.