bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased risk of death from primary hyperparathyroidism — an update
Authors: Hedbäck  , Odén  
Published: March 2003

BackgroundThe aim of this study was to investigate the risk of death among patients treated for primary hyperparathyroidism during the past decade.MethodsUsing the national patient register, all patients operated on for primary hyperparathyroidism in Sweden during 1987–94 were identified and then searched for in the national register of deaths and causes of death during the same period. The control group was the whole Swedish population, matched for age, sex and calendar year.ResultsWe found that patients treated for primary hyperparathyroidism run an increased risk of death. The risk ratios for death from cardiovascular disease were 1.71 for male and 1.85 for female patients. These estimations are of high precision because of the large patient series (n = 4461), with 95% confidence limits of 1.34–2.15 and 1.62–2.11 for men and women respectively.ConclusionThis finding, together with previous findings that parathyroid adenoma weight, serum calcium level and parathyroid hormone level are predictive of the risk of death, suggests the possibility that surgery in patients with primary hyperparathyroidism may offer not only relief from signs and symptoms but also improved prognosis.
Comparison of three fatty meals in healthy normolipidaemic men: high post‐prandial retinyl ester response to soybean oil
Authors: Mero  , Syvänne  , Rosseneu  , Labeur  , Hilden  , Taskinen  
Published: March 2003

BackgroundOral fat tolerance tests (FTTs) have been widely used as a tool to investigate post‐prandial lipaemia. However, there is no consensus regarding the type and amount of fat used in the tests.MethodsWe compared three commonly used FTTs, each containing 63 g of fat: a mixed meal, a liquid cream meal and a liquid soybean oil meal. The study group consisted of 10 healthy normolipidaemic men. We measured triglycerides (TGs), retinyl esters (REs), apolipoprotein E (apoE), apolipoprotein B‐48 (apoB‐48) and apolipoprotein B‐100 (apoB‐100) in plasma and in triglyceride‐rich lipoprotein (TRL) fractions separated by density‐gradient ultracentrifugation at baseline and 3, 4, 6, and 8 h after the FTTs.ResultsWe observed similar TGs, apoE, apoB‐48 and apoB‐100 responses after all three FTTs, despite the different fatty acid composition of the meals. In contrast, the commonly used marker for exogenous particles, RE, differed clearly when polyunsaturated (soybean oil) and saturated fat (cream or mixed meal) were used. The RE response in plasma (P < 0.005, repeated measures
ANOVA), in chylomicrons (P < 0.013) and in very low‐density lipoprotein (VLDL) 1 (P < 0.017), as well as the RE area under the incremental curve in plasma and chylomicron fractions, were markedly increased after the soybean oil meal compared with the mixed meal and cream meal tests. The peak of RE response occurred parallel to the responses of other markers (i.e. TG or apoB‐48) of post‐prandial TRL during soybean oil meal. In contrast, RE peak concentration was delayed after saturated fat‐containing meals. After soybean oil, FTT plasma cholesterol concentration was lower and the chylomicron cholesterol concentration was higher compared with mixed or cream meals, but no differences were detected in post‐prandial high‐density lipoprotein (HDL)‐cholesterol concentration.ConclusionWhen the amount of fat is similar, post‐prandial responses of TG, apoE, apoB‐48, apoB‐100 and HDL‐cholesterol were comparable after different FTTs.
Cardiac natriuretic peptides for diagnosis and risk stratification in heart failure: influences of left ventricular dysfunction and coronary artery disease on cardiac hormonal activation
Authors: Selvais  , Donckier  , Robert  , Laloux  , Van Linden  , Ahn  , Ketelslegers  , Rousseau  
Published: March 2003

BackgroundCardiac natriuretic peptides are activated in heart failure. However, their diagnostic and prognostic values have not been compared under the routine conditions of an outpatient practice.MethodsWe studied the diagnostic and prognostic value of plasma N‐ and C‐terminal peptides of the atrial natriuretic factor prohormone (N‐proANF and ANF respectively) and brain natriuretic peptide (BNP) to evaluate the severity of congestive heart failure (CHF) as reflected by the New York Heart Association (NYHA) classification and to predict its 2‐year mortality. Peripheral plasma concentrations of the three natriuretic peptides were measured in 27 normal subjects (CTR), in 32 patients with coronary artery disease (CAD) and normal left ventricular ejection fraction and in 101 patients with chronic CHF in functional classes I and II (n = 61) or III and IV (n = 40).ResultsPlasma concentrations of the three peptides increased in the presence of CHF in relation to its severity (P < 0.01). BNP was unable to distinguish CTR from CAD, just as ANF could not differentiate CAD from CHF I–II; only N‐proANF displayed a significant and continuous increase from CTR to CAD, CHF I–II and III–IV. Receiver‐operating characteristic curves showed better evaluation of the degree of CHF by BNP than by ANF or ejection fraction (P < 0.05). Assessment of the 2‐year prognosis revealed that N‐proANF and BNP were the best independent predictors of outcome after the NYHA classification. These peptides identify a very high‐mortality group.ConclusionPlasma N‐proANF and BNP concentrations are good indicators of the severity and prognosis of CHF in an outpatient practice. CAD does not stimulate BNP as long as ventricular dysfunction is not present, although increased N‐proANF levels in this setting suggest an early humoral activation.
Plasma and platelet ascorbate pools and lipid peroxidation in insulin‐dependent diabetes mellitus
Authors: Seghieri  , Martinoli  , Di Felice  , Anichini  , Fazzini  , Ciuti  , Miceli  , Gaspa  , Franconi  
Published: March 2003

BackgroundAs diabetes mellitus represents a situation in which production of peroxides is increased, the aim of this study was to investigate the relationship between plasma and platelet levels of ascorbic acid (AA)/dehydroascorbic acid (DHA) and those of malonyldialdehyde (MDA), an indirect marker of lipoperoxides, both assayed using high‐performance liquid chromatography (HPLC), in 59 patients with insulin‐dependent diabetes mellitus (IDDM) compared with 51 healthy control subjects matched for sex, age, smoking habits, as well as for dietary intake of energy, alcohol and vitamin C.ResultsMean plasma and platelet MDA were significantly higher in the patients affected with IDDM than in control subjects. Moreover, the diabetic group was characterized by a huge decrease in plasma AA [8.45 ± 5.5 μmol L−1 (SD) vs. 33.4 ± 7.6 μmol L−1, P = 0.0001], mirrored by a significant increase in plasma DHA (11.9 ± 3.9 μmol L−1 vs. 3.9 ± 2.5 μmol L−1, P = 0.0001). No detectable DHA was observed in the platelets from both diabetic and control subjects, whereas AA was significantly increased in platelets from diabetic patients compared with control subjects (42.6 ± 7.4 vs. 34.8 ± 5.1 nmol 10−9 platelets, P = 0.0001). Platelet AA in the diabetic group was significantly inversely correlated with glycated haemoglobin (r = −0.34; P = 0.04) and directly with plasma AA (r = 0.39; P = 0.02), the sum of plasma AA + DHA (r = 0.44; P = 0.009) and with platelet MDA (r = 0.38; P = 0.02).Conclusion(a) The ratio plasma AA/DHA is significantly lowered in IDDM in association with an increase in MDA levels; (b) only AA is detected in platelets, being augmented in the diabetic group; (c) plasma ascorbate depletion does not reflect platelet levels of AA; and, finally, (d) metabolic control, as well as intracellular lipoperoxides, modulates platelet AA in IDDM.
Transdermal nicotine inhibits interleukin 2 synthesis by mononuclear cells derived from healthy volunteers
Authors: Van Dijk  , Meijssen  , Brouwer  , Hop  , Van Bergeijk  , Feyerabend  , Wilson  , Zijlstra  
Published: March 2003

BackgroundSmoking has either a beneficial or harmful effect on the course and recurrence of ulcerative colitis (UC) and Crohn's disease respectively. Transdermal application of nicotine had similar effects in UC and therefore was considered to be an effective basic drug that could be further developed in the search for new compounds in the treatment of acute exacerbations of corticosteroid‐resistant UC. To clarify the hypothesis that nicotine exerts its anti‐inflammatory effect in UC through selective inhibition of T‐cell‐derived cytokine synthesis, we studied in vivo effects of nicotine on cytokine production by human non‐adherent mononuclear cells isolated from peripheral blood in a randomized, double‐blind, placebo‐controlled trial.MethodsHealthy non‐smoking volunteers applied for 2 weeks of nicotine patches (n = 12) with incremental doses of nicotine during the first week to achieve a maintenance dose of 15 mg per day, or placebo (n = 12). Blood was obtained before treatment and 1, 2, 3 and 6 weeks after the start of treatment. Cells were cultured in the absence or presence of phytohaemagglutinin for 48 h, and total amounts of interleukin 2 (IL‐2), IL‐4, IL‐10, IL‐13, interferon γ (IFN‐γ) and tumour necrosis factor alpha (TNF‐α) were measured.ResultsTransdermal nicotine caused a significant inhibition of IL‐2 after 2 weeks' treatment compared with the placebo group. In addition, a diminished production of IL‐10 and TNF‐α in comparison with day 0 was observed.ConclusionThe beneficial effect of transdermal nicotine in ulcerative colitis may be mediated by a selective inhibition of the IL‐2 production by mucosal mononuclear cells, which could result in diminished cell proliferation and consequently a reduction in the inflammatory process.
Impaired release of tissue plasminogen activator from the endothelium in Graves' disease — indicator of endothelial dysfunction and reduced fibrinolytic capacity
Authors: Li  , Chen  , Tan  , Wang  , Liang  , Sun  
Published: March 2003

BackgroundPatients with hyperthyroidism have increased plasma levels of von Willebrand factor (vWF). Changes in tissue plasminogen activator (t‐PA) and plasminogen activator inhibitor (PAI‐1), another two endothelium‐derived proteins and modulators of blood fibrinolytic activity, have not been reported in hyperthyroidism.MethodsThe release of t‐PA by vascular endothelial cells after venous occlusion, basal blood concentrations of t‐PA, PAI‐1 and vWF were studied in 33 patients with hyperthyroidism, with most of them followed up 30 days after iodine radiotherapy.ResultsCompared with control subjects, both the basal t‐PA levels in plasma and the increase in t‐PA levels with venous occlusion were significantly decreased in patients (P < 0.001), whereas plasma PAI‐1 and vWF levels were increased greatly (P < 0.001). At follow‐up, patients with normal plasma free thyroxine (T4) and total tri‐iodothyronine (T3) showed similar plasma levels of t‐PA, PAI‐1, vWF and release of t‐PA from endothelial cells as the control subjects (P > 0.05). In those with persistent elevated T4 or T3 levels, however, the basal plasma t‐PA level and the released t‐PA from endothelial cells during venous occlusion were significantly lower than in the control subjects (P < 0.001 and P < 0.005), and blood concentrations of PAI‐1 and vWF did not return to the normal range (P < 0.001 and P < 0.001). In all patients, serum thyroid hormone concentrations were inversely correlated with basal plasma t‐PA (T4: r = –0.549, P < 0.001; T3: r = –0.463, P < 0.001) and released t‐PA by endothelial cells (T4: r = –0.505, P < 0.001; T3: r = –0.450, P < 0.001) but strongly correlated with plasma PAI‐1 (T4: r = 0.613, P < 0.001; T3: r = 0.577, P < 0.001) and vWF (T4: r = 0.457, P < 0.001; T3: r = 0.564, P < 0.001).ConclusionHyperthyroid patients may experience vascular endothelial dysfunction and reduced fibrinolytic activity in blood.
Skeletal muscle metabolic characteristics before and after energy restriction in human obesity: fibre type, enzymatic β‐oxidative capacity and fatty acid‐binding protein content
Authors: Kempen  , Saris  , Kuipers  , Glatz  , Van Der Vusse  
Published: March 2003

BackgroundSkeletal muscle has the ability to adapt as result of dietary, hormonal or pharmacological interventions affecting energy metabolism. The aim of the present study was to investigate the effects of energy restriction on skeletal muscle metabolic characteristics in obese women.MethodsThe effects of 8 weeks' energy restriction on body composition, energy expenditure and skeletal muscle characteristics were investigated in 28 healthy obese women. Subjects were aged 37.9 ± 1.5 years and had a body mass index of 32.0 ± 0.8 kg m−2.ResultsEnergy restriction (2800 kJ day−1) resulted in a 10.8 ± 0.5 kg weight loss consisting of 8.6 ± 0.5 kg of fat mass and 2.2 ± 0.3 kg of fat‐free mass. Basal respiratory exchange ratio, sleeping metabolic rate and exercise‐induced thermogenesis significantly declined in response to the diet. These changes were accompanied by an increase (P = 0.038) in the skeletal muscle content of cytosolic fatty acid‐binding protein (H‐FABP), whereas no changes occurred in fibre type distribution or activities of enzymes reflecting β‐oxidation and mitochondrial density (3‐hydroxyacyl‐CoA dehydrogenase and citrate synthase respectively).ConclusionThe results suggest that increased capacity of intracellular fatty acid transport in skeletal muscle cells is involved in the physiological adaptations of fat metabolism to energy restriction in obese female subjects.
DALI—the first human whole‐blood low‐density lipoprotein and lipoprotein (a) apheresis system in clinical use: procedure and clinical results
Authors: Dräger  , Julius  , Kraenzle  , Schaper  , Toepfer  , Zygan  , Otto  , Steinhagen‐Thiessen  
Published: March 2003

BackgroundThe DALI low‐density lipoprotein (LDL) apheresis system is the first whole‐blood apheresis system in regular clinical use. DALI stands for direct adsorption of lipoproteins, which describes the basic principle of operation of this newly developed LDL apheresis procedure.MethodsThe selective removal of LDLs and lipoprotein (a) [Lp(a)] is performed in human whole blood by adsorption onto polyacrylate‐coated polyacrylamide beads in an adsorber. This article describes the results of the first open multicentre clinical trial in 14 patients in whom the safety and the efficacy of the system were tested. All patients were treated on average 17 times on a weekly basis. In total, 238 sessions were carried out during the study without severe side‐effects. On average, 7675 mL of the patients‘ whole blood was processed in about 2 h. Anticoagulation in the extracorporeal system was carried out by first giving a heparin bolus followed by continuous addition of an acid citrate dextrose (ACD‐A) infusion during the treatment.ResultsThe processing of nearly 1.6 times the patient blood volumes resulted in a reduction in the median LDL‐cholesterol level by 66–77% (dependent on the system configuration). The Lp(a) concentrations were reduced by 59–73% (dependent on the system configuration). HDL‐cholesterol, blood cell count and the other clinical parameters were not significantly affected.ConclusionBased on this short‐term evaluation, the DALI apheresis system is a well‐tolerated, effective and simple way of reducing LDL and Lp(a) in human whole blood. The system has been introduced to clinical practice. However, to use the DALI apheresis system in clinical routine, further evaluation of long‐term effects is required.
Dynamics of reactive oxygen intermediate production in human glioma: n‐6 essential fatty acid effects
Authors: Leaver  , Williams  , Ironside  , Miller  , Gregor  , Su  , Prescott  , Whittle  
Published: March 2003

BackgroundReactive oxygen intermediates (ROIs) are important signals controlling cell growth and cell death. Local essential fatty acid (EFA) deficiencies in tumour cells may limit tumour ROI generation. This deficiency may be rectified by the addition of exogenous EFA.Materials and methodsThe n‐6 EFA effects on tumour ROIs were analysed in terms of kinetics, dose–response and individual cell type responses using flow cytometry of intracellular 2′,7′‐dichlorofluorescin oxidation. ROI formation in 30 gliomas and five paired samples of normal brain tissue, > 500 000 cells per specimen, was analysed every 10 s for 0–25 min.ResultsTumour cell basal ROI was lower than normal brain tissue ROI from the same subjects (P < 0.00002). Normal and tumour cell ROIs were stimulated by 4–40 μmol L−1n‐6 EFAs, arachidonic acid (AA) and gamma‐linolenic acid (GLA). The stimulated ROI rate was exponential, with the maximum dependent on EFA concentration and tumour grade.ConclusionsEFAs stimulated tumour cells more than normal cells (P < 0.0000017, n = 71) and increased ROIs in glial fibrillary acidic protein‐positive cells in tumours. This indicated high sensitivity of glioma cell ROIs to n‐6 EFAs.
Increased frequency of the HLA‐DR15 (B1*15011) allele in German patients with self‐limited hepatitis C virus infection
Authors: Lechmann  , Schneider  , Giers  , Kaiser  , Dumoulin  , Sauerbruch  , Spengler  
Published: March 2003

BackgroundA genetically determined resistance or susceptibility to chronic hepatitis C virus infection (HCV) may make an important contribution to the course of liver disease and may be linked to the human major histocompatibility complex.DesignTwenty‐one subjects with self‐limited HCV infection as assessed by the presence of HCV antibodies, absence of HCV‐RNA and normal levels of aminotransferases for 2 years were identified from a large pool of blood donors. The frequency of HLA serotypes of these individuals was compared with 49 consecutive patients with chronic hepatitis C.ResultsWe detected a significantly higher prevalence of HLA‐DR15 in patients with self‐limited HCV infection than in patients with chronic hepatitis C (10/21 vs. 6/49; relative risk 6.5; P = 0.02; corrected for multiple comparisons). To confirm HLA assignments by serotyping we also performed sequencing of HLA‐DR types in the 27 patients (9 with self‐limited infection, 18 with chronic hepatitis C) who had been enrolled during 1995–96. This analysis confirmed the predominance of HLA‐DR15 (HLA‐DRB1*15011) in self‐limited HCV infection (4/9 vs. 1/18; relative risk 13.6; P = 0.03).ConclusionsOur data suggest that HLA‐DR15 (B1*15011) might constitute an important genetic factor for the elimination of the hepatitis C virus in Germany.
Increased luminal nitric oxide concentrations in the small intestine of patients with coeliac disease
Authors: Everts  , Stotzer  , Olsson  , Kilander  , Pettersson  
Published: March 2003

BackgroundInflammation is known to be associated with enhanced nitric oxide production. A role for nitric oxide in coeliac disease has been suggested because of increased expression of the inducible isoform of nitric oxide synthase in the small intestine of patients with untreated coeliac disease.DesignDuring small bowel endoscopy in 11 control subjects, 10 patients with untreated coeliac disease and seven patients with treated coeliac disease, gas was aspirated from different parts of the upper gastrointestinal tract and immediately analysed using a chemiluminescence technique. Luminal nitric oxide concentrations were also quantified in 13 control subjects who had undergone colonoscopy.ResultsJejunal luminal nitric oxide concentrations were more than 20 times higher in patients with coeliac disease than in normal control subjects (mean 755 ± 173 ppb, range 215–1690 ppb, vs. mean 31 ± 9 ppb, range 1–83 ppb, P < 0.001). Jejunal luminal nitric oxide levels in patients with treated coeliac disease (mean 54 ± 18 ppb, range 3–126 ppb) did not differ from those of control subjects.ConclusionsThis study shows that intraluminal jejunal nitric oxide concentrations are significantly increased in patients with untreated active coeliac disease.
Methylenetetrahydrofolate reductase polymorphism, plasma homocysteine and age
Authors: Todesco  , Angst  , Litynski  , Loehrer  , Fowler  , Haefeli  
Published: March 2003

BackgroundElevated fasting levels of total homocysteine are now accepted as an independent risk factor for the development of arteriosclerotic vascular diseases. A polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR), caused by the C677T point mutation, leads to increased thermolability of the enzyme, with reduced enzyme activity. We studied the frequency of this mutation in different groups of the Swiss adult population.Patients and methodsDNA from 361 subjects was screened for the thermolabile MTHFR variant with PCR. Included were healthy subjects without vascular disease (n = 118), older healthy subjects (n = 106), patients with coronary artery disease (CAD, n = 75), and patients with peripheral arterial occlusive disease (PAOD, n = 63).ResultsIn the different groups studied, homozygosity for the mutation ranged from 4.8 to 16.2%, with a frequency of 16.2% in the healthy cohort. The allele frequencies of the thermolabile allele were 38.5 and 27.3 in young and old controls, and 37.3 and 33.3 in CAD and PAOD patients. In the healthy younger subjects the mutant allele was 1.4 times more frequent compared to the older subjects (P = 0.01). No difference in either MTHFR genotype distribution (P = 0.33) or allele frequencies (P = 0.48) between patients and controls was found. Except for the PAOD group with elevated tHcy levels for the +/+ carriers compared to the other genotypes, no statistically significant difference was found comparing homocysteine levels with genotype.ConclusionThis study shows no link between the mutation and the occurrence of vascular disease but we found evidence pointing to a correlation between the mutation and longevity in our population.
Paraoxonase activity in two healthy populations with differing rates of coronary heart disease
Authors: Mackness  , Mackness  , Durrington  , Arrol  , Evans  , McMaster  , Ferrières  , Ruidavets  , Williams  , Howard  
Published: March 2003

BackgroundThe rate of coronary heart disease is over three‐fold greater in Belfast than in Toulouse and the excess risk cannot be totally explained by ‘classical’ risk factors such as total cholesterol, LDL‐cholesterol, smoking, etc.DesignThe effect of the human serum paraoxonase (PON1) 192‐genetic polymorphism on plasma lipid and lipoprotein concentrations and on PON1 activity and concentration was investigated in 186 randomly selected healthy subjects from Toulouse and 165 from Belfast.ResultsThe frequency of the R allele of PON1, which has been related to the risk of coronary heart disease, was significantly higher in Belfast (0.33) than in Toulouse (0.24; χ2 = 7.229, P = 0.0072). Subjects from Belfast also had significantly higher serum cholesterol, triglycerides, LDL‐cholesterol, and apolipoprotein B, and significantly lower HDL‐cholesterol and apolipoprotein A1, but these lipoprotein parameters were independent of the PON1 192‐polymorphisms. PON1 activity towards paraoxon was significantly higher in the Belfast population than in Toulouse (median values: 179.7 vs. 129.4 nmol min−1 mL−1 serum, respectively; P < 0.05), which is consistent with our finding of a greater prevalence of the R allele. The median serum concentration of PON1 was 56.3 μg mL−1 in Belfast, which was significantly lower (P < 0.005) than the level of 71 μg mL−1 in Toulouse.ConclusionsOur results thus provide further support for the hypothesis that populations at increased CHD risk have diminished serum PON1 concentration and an increased prevalence of the R allele of PON1. They are also consistent with reports that the ability of PON1 to hydrolyse paraoxon is inversely related to its capacity to hydrolyse lipid‐peroxides, and thus to its antiatherogenic action.