bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract. 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.ObjectivesSince 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.DesignClinical study of consecutive patients.SettingThe catchment area of Sahlgrenska University Hospital, Göteborg.SubjectsA total of 112 patients with suspected cobalamin deficiency who had not previously undergone gastrointestinal surgery.InterventionsGastroduodenoscopy 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 measuresNumber of patients with gastric body atrophy identified with the combination of MMA and Hcy, and pepsinogen A combined with pepsinogen C or gastrin.ResultsAbout 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.ConclusionsPepsinogen 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

Abstract.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

Abstract.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.