bluuebunny/crossref_metadata_2025_split huggingface dataset:
High serum laminin concentrations in patients with Candida sepsis
Authors: Presterl  , Lassnigg  , Mueller‐Uri  , Wenisch  , El‐Menyawi  , Graninger  
Published: March 2003

BackgroundLaminin, a major component of the basement membrane, plays a critical role in normal cell adhesion and also during tissue invasion of pathogenic microorganisms.Materials and methodsSerum laminin concentrations were determined in 19 patients with Candida albicans sepsis, in 13 patients with bacterial sepsis and in 20 noninfectious controls.ResultsSerum laminin concentrations of both, patients with candidal and bacterial sepsis, were significantly elevated compared to the controls (486 ng mL−1 [155–924], median [range]; P < 0.01). Laminin concentrations were significantly higher in patients with Candida sepsis than in patients with bacterial sepsis on day 1 (2565 ng mL−1 [659–6064] vs. 994 ng mL−1 [386–2064]; P < 0.01), day 7 (1594 ng mL−1 [607–4611] vs. 684 ng mL−1 [284–1920]; P < 0.05) and day 14 (1444 ng mL−1 [202–2131] vs. 386 ng mL−1 [180–1658]; P < 0.05).ConclusionsLaminin serum concentrations might be useful to differentiate nonbacterial, bacterial and fungal etiology.
Intrapleural administration of tumour necrosis factor‐alpha (TNFα) in patients with mesothelioma: cytokine patterns and acute‐phase protein response
Authors: Stam  , Swaak  , Kruit  , Stoter  , Eggermont  
Published: March 2003

BackgroundTumour necrosis factor‐alpha (TNFα) has been found to be very effective in the isolated limb perfusion setting for advanced extremity tumours. In a phase I study of intrapleural administration of TNFα 5 patients were followed for inflammatory response patterns.Patients and methodsMalignant mesothelioma patients were treated with repeated intrapleural administration of 0.1–0.2 mg recombinant TNFα. Samples of serum and pleural fluid were taken at different time‐points before and after TNFα‐administration. Levels of TNFα, interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), C‐reactive protein (CRP) and secretory phospholipase A2 (sPLA2) were measured using enzyme‐linked immunosorbent assays (ELISAs). Alpha 1‐acid glycoprotein (α1‐AG) was measured by nephelometry.ResultsIn pleural fluid TNFα and IL‐8 reached peak levels, up to 50–700 ng mL−1 and 6–60 ng mL−1, respectively, 24 h after administration of TNFα. IL‐6 (peak levels up to 250 ng mL−1) and sPLA2 peaked after 48 h. A slower and less dramatic pattern was observed for the levels of CRP and α1‐AG. In serum no detectable levels of TNFα and no IL‐8 were observed, whereas serum levels of IL‐6, sPLA2 and CRP showed a clear increase after intrapleural administration of TNFα. Cytokines and acute‐phase proteins showed the same pattern during subsequent cycles even up to 12 cycles. Tumour regression was not observed.ConclusionsIn the setting of a phase I study of repetitive intrapleural administration of TNFα in mesothelioma patients, we studied the characteristics of the inflammatory response. Intrapleural administration was followed by a clear inflammatory response locoregionally. In spite of TNFα peak levels as high as 700 ng mL−1 systemic levels were never detectable. The secondary cytokine response led to very high intrapleural IL‐6 and IL‐8 levels. Systemically IL‐8 levels were never detectable whereas high IL‐6 levels were induced systemically initially, with a decreased response to each intrapleural TNFα administration over time. The acute‐phase response in contrast remained remarkably constant throughout the course of repeated intrapleural administrations of TNFα. Intrapleural administration of TNFα is well tolerated but associated with inconsistent and rather moderate impact on production of pleural fluid. This can be achieved by other simpler and cheaper treatment, thus we see no justification for further studies.
The 16p11 breakpoint in myxoid liposarcomas might affect the expression of the LRP gene on 16p11.2 encoding the multidrug resistance associated major vault protein
Authors: Plaat  , Molenaar  , Sagrudny  , Bohle  , Mastik  , Hoekstra  , Van der Graaf  , Hollema  , Van Den Berg  
Published: March 2003

BackgroundChromosome breakage could influence the expression of genes. This has been noticed in specific cases of acute myeloid leukaemia, where the 16p13 breakpoint affects the expression of the multidrug resistance related protein (MRP). Myxoid liposarcomas (LPS) are characterized by the t(12; 16)(q13; p11), which leads to the formation of a FUS‐CHOP fusion transcript. This study investigates the relationship between the cytogenetically detected breakpoint 16p11 in myxoid LPS, the presence of the FUS‐CHOP fusion transcript in nonmyxoid LPS and the expression of the lung resistance major vault protein (LRP) gene on 16p11.2.Materials and methodsOf 16 cases with a diagnosis of a (possible) liposarcoma with an abnormal karyotype, fresh frozen tumour material was available for immunohistological detection of LRP. Cases without a cytogenetically detected t(12; 16)(q13; p11), were analyzed for the presence of a FUS‐CHOP fusion transcript by RT‐PCR.ResultsIn all 9 myxoid LPS a t(12; 16)(q13; p11) was found and LRP expression was absent or low. In none of the remaining 7 cases was a FUS‐CHOP fusion transcript found, and four tumours were LRP positive (P = 0.02). LRP expression in myxoid LPS (mean: 1.3%) was lower (P = 0.07) than in the nonmyxoid tumours (mean: 35.7%).ConclusionsThese observations indicate a relation between the t(12; 16)(q13; p11), leading to a FUS‐CHOP fusion transcript in myxoid LPS, and the low or absent expression of the LRP‐gene located on 16p11.2.
Susceptibility to neuromediated syncope after acute myocardial infarction
Authors: Wa¸sek  , Kułakowski  , Czepiel  , Kłosiewicz‐Wa¸sek  , Budaj  , Soszyńska  , Maciejewski  , Stec  , Ceremużyński  
Published: March 2003

BackgroundSyncope after acute myocardial infarction (AMI) is a common clinical problem. It may be hypothesised that remodelling and neurohormonal changes following AMI may predispose to neuromediated syncope.DesignTo address this issue we prospectively evaluated the incidence of positive results of head‐up tilt‐table testing in 40 patients following AMI and 40 age and sex matched controls without a history of syncope. The mechanisms of tilt‐induced changes in autonomic tone were assessed using spectral analysis of heart rate variability. The patients were followed‐up for one year.ResultsPositive results of tilt‐test occurred in 4 (10%) controls and 13 (33%) AMI patients (P = 0.01). No significant differences in sympathovagal interaction (assessed by a low frequency/high frequency ratio) were detected between the groups before tilting (2.9 ± 1.9 vs. 3.1 ± 2.2; NS). However, dynamic changes of this parameter differed significantly during the first 5 symptomless minutes of the active phase of tilt‐test. The ratio increased in the majority of controls (87%) and decreased in the majority of patients (62%) (P < 0.0001). During one year follow‐up, syncope or presyncope occurred in 10 (25%) AMI patients but did not occur in any control subject (P < 0.001). The sensitivity, specificity and predictive accuracy of an early tilt‐test after AMI for the prediction of syncope or presyncope was 70%, 80% and 78%, respectively.ConclusionPatients after AMI are prone to neuromediated reactions. Sympathetic withdrawal seems to be the most likely mechanism of syncope. The role of tilt testing for identification of patients susceptible to syncope or presyncope after AMI needs further investigation.
Microvascular angina (cardiological syndrome X) per se is not associated with hyperinsulinaemia or insulin resistance
Authors: Cavallo Perin  , Pacini  , Giunti  , Comune  , Conte  , Cassader  , Pagano  
Published: March 2003

BackgroundMicrovascular angina has been found to be associated with insulin resistance. However, many factors known to affect insulin sensitivity were not excluded in patient selection. We aimed to evaluate whether microvascular angina is per se associated with insulin resistance.Materials and methodsWe performed a Frequently Sampled Intravenous Glucose Tolerance Test (0.33 g kg−1 b.w.) in 10 normal weight and normotensive patients with microvascular angina, with normal glucose tolerance and normal plasma lipids. Ten healthy subjects, comparable for age, sex, body mass index, blood pressure and plasma lipids, were used as control group.ResultsFasting serum glucose (4.49 ± 0.2 SEM vs. 4.52 ± 0.13 mmol L−1, P = 0.9), insulin (39.46 ± 3.68 SEM vs. 47.12 ± 4.6 pmol L−1, P = 0.21) and C‐peptide (0.56 ± 0.05 SEM vs. 0.53 ± 0.05 nmol L−1, P = 0.68) values, as well as estimated parameters of insulin secretion and hepatic insulin extraction were similar in the two groups. Insulin sensitivity values (median, range) were also similar in the patients and control subjects (5.76 (3.39–12.30) vs. 7.54 (3.68–13.89. 10−4. min−1/(μU/mL), P = 0.97).ConclusionMicrovascular angina per se is not associated with hyperinsulinaemia or insulin resistance when other confounding factors are excluded in patient selection.
Polymorphisms in the vitamin D receptor gene and bone mass, bone turnover and osteoporotic fractures
Authors: Langdahl  , Gravholt  , Brixen  , Eriksen  
Published: March 2003

BackgroundVitamin D is essential for normal bone metabolism. Polymorphisms in exon 2, intron 8 and exon 9 of the vitamin D receptor (VDR) gene have previously been found to be associated with bone mass and bone turnover.Materials and methodsWe examined the effect of these polymorphisms, separately and in combination, on bone mineral density (BMD), bone turnover, and the prevalence of osteoporotic fractures in 192 osteoporotic patients and 207 normal controls. The four polymorphisms were determined by RFLP using Fok I (T2‐C), Bsm I (intron 8), Apa I (intron 8) and Taq I (T1055‐C) after PCR.ResultsWe did not find any association between the Fok I polymorphism and bone mass, bone turnover or prevalence of osteoporotic fractures. We found that BB + Bb‐genotypes were more frequent in patients with osteoporotic fractures (χ2 = 3.50, P = 0.06). Furthermore, BMD of the intertrochanteric region (P < 0.0001,
anova) as well as the total hip (P < 0.01,
anova) were higher in individuals with the bb‐genotype. The Apa I and the Taq I polymorphisms were not distributed differently among osteoporotic patients and normal controls. Apa I was not associated with differences in BMD. BMD of the intertrochanteric region was higher in individuals with the TT‐genotype compared with individuals with the Tt‐ or tt‐genotypes (P < 0.01,
anova), while no differences could be demonstrated in BMD of the lumbar spine, femoral neck, trochanter or Wards triangle. Combining the genotypes generally reflected the differences caused by the Bsm I polymorphism.ConclusionWe have found that the B‐allele of the Bsm I polymorphism in the 3′ untranslated region of the VDR was associated with low BMD at the hip, and tended to be associated with osteoporotic fractures. The translation initiation polymorphism in the VDR does not affect BMD and is not associated with osteoporotic fractures in men or women.
Proximal and distal gut hormone secretion in slow transit constipation
Authors: Penning  , Delemarre  , Bemelman  , Biemond  , Lamers  , Masclee  
Published: March 2003

BackgroundIt has been suggested that slow transit constipation might be part of a pan‐enteric disorder. Gastrointestinal peptides are involved in regulation of motility.DesignIn the present study we have evaluated whether plasma levels of proximal and distal gut hormones in the fasting state, and for 120 min after a solid meal in 29 patients with slow transit constipation are different from those obtained from 29 healthy controls. Plasma levels of the gut hormones cholecystokinin, gastrin, pancreatic polypeptide, motilin, neurotensin and peptide YY were determined using sensitive radioimmunoassays. In the patient group, oro‐caecal transit time was determined by means of the hydrogen breath test on a separate test day. The results of transit were related with postprandial hormone secretion.ResultsFasting plasma levels of cholecystokinin and pancreatic polypeptide were significantly (P < 0.05) increased in constipated patients. Postprandially, secretion of pancreatic polypeptide and cholecystokinin was significantly (P < 0.05) increased in the patients, while secretion of peptide YY was significantly (P < 0.05) reduced. Plasma motilin levels were not different between patients and controls. Altered postprandial hormone secretion was mainly observed in constipated patients with prolonged oro‐caecal transit time.ConclusionsIn patients with slow transit constipation, fasting and postprandial secretion of proximal gut hormones apart from motilin is increased and of distal gut hormones decreased, especially in those with severely delayed intestinal transit.
Effects of nitroglycerine on cerebral blood flow velocity, quantitative electroencephalogram and cognitive performance
Authors: Siepmann  , Kirch  
Published: March 2003

BackgroundDespite the widespread use of nitroglycerine, little is known of its cerebral haemodynamic effects. The present study was undertaken to evaluate the effects of nitroglycerine on cerebral circulation and cognitive function in normal volunteers.DesignTwelve healthy male volunteers (age 25 ± 3 years; mean ± SD) received continuous intravenous infusions of nitroglycerine at 1 mg h−1 and 2 mg h−1 rates as well as placebo (0.9% saline) under randomized, double‐blind cross‐over conditions on three different occasions. A 10‐min quantitative EEG (qEEG) was recorded before, during and repeatedly after infusion. Blood flow velocity in the left arteria cerebri media (MCA) was measured simultaneously by means of transcranial Doppler sonography. Cognitive performance was assessed with a computerized test battery.ResultsAdministration of nitroglycerine caused a significant reduction of mean blood flow velocity in the left MCA. In parallel a significant increase of absolute power density < 4 Hz was noted. The latter effect was dose dependent. Cognitive functions, such as attention and memory, were not altered.ConclusionsThe decrease in cerebral blood flow velocity in the left MCA may be due to vasodilatation and/or reduction in perfusion. The concomitant increase of slow wave power in the qEEG may indicate an impairment of brain function.
Corticotropin‐releasing hormone binding to the syncytiotrophoblast membranes
Authors: Saeed B. , Fawcett M. , Self C. 
Published: March 2003

The human placenta secretes large amounts of corticotropin‐releasing hormone (CRH) which was thought to exert a paracrine action in the placenta. We have recently characterized high‐affinity binding sites for CRH in the human placenta. However, our studies utilized whole placental membranes, which did not identify the site of binding of CRH in the plasma membrane.In this study we investigated the characteristics of CRH binding to purified mother‐facing, brush border membranes (BBM) and fetus‐facing, basal plasma membranes (BPM) of the syncytiotrophoblast. The two membranes were separated by a series of differential and density‐gradient centrifugations. The purity of the membranes was determined by measuring alkaline phosphatase, as a marker of BBM and Na+/K+ATPase as a marker of BPM.Each membrane showed specific and high‐affinity binding. Scatchard analysis revealed a high‐affinity binding site for CRH with Kd of 1·0 ± 0·15 and 1·3 ± 0·176 for BBM and BPM, respectively. The maximal number of binding sites was significantly different (P < 0·01) in the two plasma membranes: Bmax of 79 ± 6·4 fmol/mg protein for BBM and 23 ± 3·9 fmol/mg protein for BPM.Both the mother‐facing and fetus‐facing membranes of the syncytiotrophoblast contain binding proteins for CRH, with significantly more binding sites on the mother‐facing membranes. The functional consequences of CRH binding could be different for the two polar membranes due to differential localization of second messenger systems between the two membrane types. It is proposed that partial purification of BBM and BPM provides a better system to study CRH action in the placenta, than whole placental membrane preparations.
Hepatic phenylalanine metabolism measured by the [13C]phenylalanine breath test
Authors: Kobayashi T. , Kubota K. , Imamura H. , Hasegawa K. , Inoue Y. , Takayama T. , Makuuchi M. 
Published: March 2003

Background The amino acid clearance test including phenylalanine is known to reflect liver functional reserve, which correlates with surgical outcome; however, the procedure is not clinically useful because of its laborious and time‐consuming nature. This study evaluates whether phenylalanine oxidation capacity measured by a breath test could reflect liver functional reserve.Design We determined phenylalanine oxidation capacity in 42 subjects using the l‐[1‐13C]phenylalanine breath test (PBT). The 13CO2 breath enrichment was measured at 10‐min intervals for 120 min after oral administration of 100 mg of

l‐[1‐13C]phenylalanine. Subjects were divided into the following three groups according to their plasma retention rate of indocyanine green at 15 min (ICG R15): Group I (ICG R15 < 10%), Group II (ICG R15 10–20%), and Group III (ICG R15 > 20%). First, we determined the parameters of the phenylalanine oxidation capacity that differentiated these groups and then, using these parameters, we compared the PBT with the ICG clearance test, Child–Pugh classification score and standard liver blood tests.Results The %13C dose h−1 at 30 min and cumulative excretion at 80 min were significantly different among the three groups (P < 0·05). These two parameters significantly correlated with the ICG R15, Child–Pugh classification score (P < 0·0001) and results of standard liver blood tests (P < 0·05).Conclusions Phenylalanine oxidation capacity measured by the PBT was reduced according to the severity of liver injury assessed by the ICG clearance test, Child–Pugh classification, and standard liver blood tests. These results indicate that the PBT can be used as a noninvasive method to determine liver functional reserve.
Fatty acid binding protein 2 and insulin resistance
Authors: Chiu K. C. , Chuang L.‐M. , Chu A. , Yoon C. 
Published: March 2003

Background An A54T polymorphism of the fatty acid binding protein 2 (FABP2) gene was found to be associated with insulin resistance in nondiabetic Pima Indians. Design This is a cross‐sectional study to examine the role of this polymorphism in insulin resistance in 71 healthy and normotensive Caucasian subjects with normal glucose tolerance. Insulin sensitivity (%S, ISIM, ISIS) and beta‐cell function (%B, dI/dG, 1stPHS, 2ndPHS) were estimated based on published models. Their genotypes were determined using a polymerase chain reaction‐restriction fragment length polymorphism assay. The relationship between genotypes and phenotypes was examined. Results After genotyping, we identified 34 AA, 32 AT and five TT subjects. The TT subjects were pooled together with the AT subjects during the analysis due to their low number. No difference was noted in gender distribution, clinical features, or fasting lipid profile between the two genotypic groups (AA vs. AT/TT). The AT/TT group had lower %S and ISIS than the AA group (P = 0·0118 and P = 0·0170, respectively). The difference in ISIM was marginal (P = 0·0544). However, no difference was noted in beta‐cell function between the two groups. Multivariate analysis revealed that this polymorphism was an independent but modest determinant for %S (P = 0·0149), ISIM (P = 0·0489) and ISIS (P = 0·0175). It independently contributed 6·04% (95% CI, 0·02–20·53%), 4·28% (95% CI, 0·08–17·63%) and 4·94% (95% CI, 0·01–18·75%) of the variation of %S, ISIM and ISIS, respectively. Conclusions We demonstrated that the A54T polymorphism at the FABP2 locus is a risk factor for insulin resistance in a Caucasian population.
Apolipoprotein E polymorphism and lithogenic factors in gallbladder bile
Authors: Fischer S. , Dolu M. H. , Zündt B. , Meyer G. , Geisler S. , Jüngst D. 
Published: March 2003

Background Associations between the polymorphism of apolipoprotein E, which plays an important role in cholesterol metabolism and cholesterol gallstone formation, have been reported recently. Patients with the apo E4 isoform showed increased numbers and cholesterol contents of their stones, a higher frequency of cholesterol crystals in bile, increased susceptibility to gallstone fragmentation by extracorporeal shock‐wave lithotripsy and an increase in recurrence rate after dissolution. A recent study, however, showed that fast cholesterol crystallization in bile is associated with multiple stones but not with apo E4. Therefore the mechanism for an increased risk of gallstone formation in patients with the apo E4 isoform still remains under debate.Design To clarify this issue we investigated 37 patients with gallstones (10 with the apo E4 allele and 27 without the allele). Gallbladder biles were examined for total cholesterol and other lipids, cholesterol saturation index, crystal observation time, crystal mass, total protein and mucin. Moreover, number of gallstones and cholesterol in gallstones was compared in both groups.Results The crystal observation time (2·5 vs. 2·0 days, median) and the cholesterol saturation index (1·34 ± 0·45 vs. 1·43 ± 0·74) did not differ significantly between the apo E4 and the non apo E4 group. Total biliary lipids (11·6 ± 3·8 vs. 9·3 ± 3·9 g 100 mL−1, P = 0·126) and total biliary cholesterol (21·8 ± 9·7 vs. 15·7 ± 7 mmol L−1, P = 0·067) tended to be elevated in the apo E4 group. Crystal mass (3·60 ± 4·10 vs. 2·38 ± 2·70 mmol L−1), biliary total protein (8·6 ± 3·5 vs. 8·3 ± 6·6 mg mL−1) and mucin (0·55 ± 0·38 vs. 0·66 ± 0·67 mg mL−1), number (solitary/multiple) of gallstones and cholesterol in gallstones were not different in both groups of patients.Conclusions In comparison to the non apo E4 patients the apo E4 group showed a trend to elevated biliary cholesterol whereas crystal observation time, cholesterol saturation index, crystal mass, number of gallstones, cholesterol content of gallstones and total protein and mucin were not different. These findings do not suggest an association of the apo E isoform and the formation of cholesterol gallstones
d‐penicillamine reduces serum oxidative stress in Alzheimer’s disease patients
Authors: Squitti R. , Rossini P. M. , Cassetta E. , Moffa F. , Pasqualetti P. , Cortesi M. , Colloca A. , Rossi L. , Finazzi‐Agro′ A. 
Published: March 2003

Abstract Background  Several lines of evidence address the emerging role for copper in Alzheimer’s disease (AD) for sustaining oxidative mechanisms. Studies indicate that peripheral markers of oxidative stress in AD patients could be informative about the pathophysiology of this brain condition. Here, we present a pilot study examining the efficacy of the copper‐chelating agent d‐penicillamine in reducing oxidative stress in AD patients.Design  Serum levels of copper sampled in AD patients and healthy controls indicate a copper homeostasis imbalance in AD. On this basis, 34 AD patients were enrolled in a 6‐month, double‐blind, placebo‐controlled trial with the copper d‐penicillamine‐chelating agent. Nine patients for each group completed the trial. Oxidative stress, trace metals and clinical parameters were evaluated.Results  At the start of the study (t0) total peroxides and copper serum content of AD patients were higher (P < 0·0001, P < 0·0001, respectively) and antioxidants were lower (P < 0·05) than in healthy controls. Copper and peroxides were correlated in the AD population (Pearson’s r = 0·61, P < 0·001). After treatment with d‐penicillamine, the extent of oxidative stress (P < 0·05) was decreased, but no difference was observed in the rate of cognitive decline.Conclusion  Data from this pilot study suggest that copper could play a role in the production of peroxides in AD, and that d‐penicillamine has an effect in reducing oxidative damage, however, results are still inconclusive in terms of drug efficacy on the clinical progression of AD. Studies with larger cohorts are needed to elucidate the real effectiveness of d‐penicillamine treatment in AD.