bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of the Rapid Protective Effect of Formoterol Dry-Powder Inhalation against Exercise-Induced Bronchospasm in Athletes with Asthma
Authors: Ferrari M. , Balestreri F. , Baratieri S. , Biasin C. , Oldani V. , Lo Cascio V. 
Published: April 2003

<i>Background:</i> Although formoterol, a new long-acting β<sub>2</sub>-adrenergic agonist, has a rapid bronchodilating action, no studies have previously examined whether it can provide equally rapid protection against exercise-induced bronchospasm (EIB). <i>Aim:</i> The aim of the study was to assess the effect of inhaled formoterol against EIB 15 min and 4 h after administration in asthmatic athletes. <i>Methods:</i> The protective effect of a formoterol (12 µg) dry-powder inhalation was evaluated in 14 EIB-positive asthmatic athletes (13 males, mean age 16.8 years), in a double-blind, placebo-controlled, two-period cross-over study. On each treatment day, the subjects underwent two cycloergometric exercise tests 15 min and 4 h after receiving formoterol or placebo. <i>Results:</i> Formoterol induced significant bronchodilation in comparison with placebo both 15 min and 4 h after administration (p = 0.007 and p = 0.004); placebo treatment had no effect on EIB, the maximum percent fall in FEV<sub>1</sub> after exercise being 29.3 ± 14.3% and 22.9 ± 13.7% at 15 min and 4 h, respectively. Formoterol offered good protection against EIB in 12 athletes (86%) who experienced a decrease in FEV<sub>1</sub> after exercise <10% both 15 min and 4 h after administration. The mean maximum percent fall in FEV<sub>1</sub> after formoterol was 5.9±7.2% at 15 min (p < 0.0001), and 5.8 ± 6.9% at 4 h (p < 0.0001). There was no statistically significant difference in resting heart rate before and after medication with placebo or formoterol, nor was the heart rate at the end of exercise significantly different on the 2 treatment days. No side effect was observed in either group. <i>Conclusions:</i> This study demonstrates that formoterol dry powder inhalation is effective in protecting asthmatic athletes as early as 15 min after dosing. Furthermore, the data confirm the long duration of its protective effect and the absence of any significant adverse effects after acute administration.
Platelet Dynamics following Allergen Challenge in Allergic Asthmatics
Authors: Sullivan P.J. , Jafar Z.H. , Harbinson P.L. , Restrick L.J. , Costello J.F. , Page C.P. 
Published: April 2003

<i>Background:</i> There is evidence that platelet activation occurs in allergic inflammation and asthma, but little is known about the role platelets play in airway inflammation associated with asthma. <i>Objectives:</i> In the present study, we have investigated the kinetics of platelet activation following allergen provocation of allergic asthmatics to determine the dynamics of platelet activation relative to changes in lung function and changes in airway inflammation. <i>Methods:</i> Changes in platelet count and haematocrit from baseline were measured during the early asthmatic response (EAR), late asthmatic response (LAR; or at corresponding time points) and at 24 h were compared between allergen- and saline-challenged groups. A subgroup of allergen-challenged asthmatics, a group of 7 challenged asthmatics and 7 controls were bronchoscoped, and BAL fluid was collected and analysed for levels of histamine and eosinophil cationic protein. <i>Results:</i> There was a fall in circulating platelet count, but not haematocrit after allergen challenge when compared with saline during the LAR or at 24 h. At 24 h FEV<sub>1</sub> had returned to within 20% of baseline in all subjects, although the thrombocytopaenia and airway inflammation persisted. <i>Conclusions:</i> Our results suggest that persistent thrombocytopaenia accompanies allergen exposure and persists beyond changes in airway obstruction at a time when airway inflammation is present. Our results provide further evidence that platelets may be involved in allergic disease.
Pyruvate Kinase Type Tumor M2 in Urological Malignancies
Authors: Hegele A. , Varga Z. , Kosche B. , Stief T. , Heidenreich A. , Hofmann R. 
Published: April 2003

<i>Introduction: </i>The dimeric form of pyruvate kinase type M2 is overexpressed in tumor cells (TuM2-PK). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for renal cell carcinoma (RCC), transitional cell carcinoma of the bladder (TCC) and prostate cancer (PCA) by using a commercially available enzyme-linked immunosorbent assay for detection of TuM2-PK in plasma. <i>Material and Methods:</i> The TuM2-PK concentration in EDTA plasma was determined quantitatively and immunologically using an ELISA (ScheBo<sup>®</sup>Tech, Germany). We measured the TuM2-PK plasma levels of 83 patients with RCC, 30 patients with TCC and 30 patients with PCA before any therapy. 100 patients with various non-malignant urological disorders were recruited as the control group. <i>Results:</i> Only patients with RCC showed significantly elevated plasma levels of TuM2-PK compared to the control group (p < 0.01). We found a sensitivity of 42.6% and a specificity of 80.4% using a cut-off value of 15 U/ml (manufacturer’s recommendation). During follow-up, only 50% showed increasing plasma levels of TuM2-PK in case of metastases. Significant differences could not be detected in either TCC or PCA. <i>Conclusions:</i> Our data suggest that TuM2-PK is not a useful marker for TCC and PCA. Due to low sensitivity and specificity, TuM2-PK is not suitable for the diagnosis of RCC. Whether TuM2-PK may be useful in advanced RCC to control success of palliative treatment regimens is still unclear.
Synapse Loss May Be a Minor Contributor to Decreased Regional Cerebral Blood Flow in Alzheimer Disease
Authors: Bigio Eileen H. , Reisch Joan S. , White 3rd Charles L. , Satumtira Sivapong , Sontag Estelle , Bonte Frederick J. 
Published: April 2003

In this study we tested the hypothesis that synapse loss contributes to decreased regional cerebral blood flow (rCBF) in Alzheimer disease (AD). We compared antemortem rCBF and postmortem analysis of synaptophysin, as a measure of synapse loss, in 13 cases of AD. rCBF studies were performed using inhaled xenon gas (Xe-133), which yields quantitative results. Synapse loss was evaluated in postmortem brain samples using an enzyme-linked immunosorbant assay (ELISA) that measures synaptophysin, with results expressed as picomoles synaptophysin/10 mg brain. Synaptophysin was expressed either as concentration (QS method) or as the ratio of the concentration to the combined results in frontal, temporal and parietal lobe (RS method). There was no correlation between synapse loss and rCBF using the QS method and only borderline significance between right SPECT and right temporal synaptophysin using the RS method. The results of this study suggest that synapse loss may be a minor contributor to the decreased rCBF observed in AD.
Circulating Intercellular Adhesion Molecule-1 in Chronic Hepatitis C Patients with Normal or Elevated Aminotransferase before and after Alpha-Interferon Treatment
Authors: Montalto Giuseppe , Giannitrapani Lydia , Soresi Maurizio , Florena Ada , Di Martino Daniela , Franco Vito , Carroccio Antonio , Cervello Melchiorre 
Published: April 2003

<i>Objectives:</i> Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during α-interferon (IFN) therapy. Immunohistochemical localization of ICAM-1 was also performed on liver tissue specimens of both groups. <i>Methods:</i> Sixty subjects were divided into 3 groups: group A included 19 patients with CH-C and persistently normal aminotransferase; group B included 21 patients with CH-C and persistently elevated aminotransferase levels, and group C included 20 healthy subjects representing the control group. The first two groups were treated with recombinant α-IFN 2b at a dose of 6 MU 3 times a week for 3 months and followed up with 3 MU 3 times a week for another 3 months. <i>Results:</i> Baseline values of serum ICAM-1 in groups A and B were significantly higher than those in group C (p < 0.0001). The median baseline value of sICAM-1 in group A (525.0 ng/ml) was lower than that of group B (561.0 ng/ml), but the difference was not statistically significant. Furthermore, there was a trend toward higher ICAM-1 values as histological severity increased (Mantel-Haenszel χ<sup>2</sup> 8.8, p < 0.003). Post-treatment sICAM-1 serum values showed a marked decrease in both groups, but only among responder patients, while ICAM-1 levels were unchanged in non-responders. Immunohistochemical localization showed no staining for ICAM-1 in normal liver specimens, while there was a quite similar staining for ICAM-1 in the two groups of patients, consistent with an inflammatory process. <i>Conclusions:</i> This study shows that circulating ICAM-1 levels in most patients with CH-C and persistently normal aminotransferase are higher than those in a control group and the fact that ICAM-1 molecules are also expressed on the hepatocyte membrane suggests that they could play an important role, in association with other molecules, in the intercellular adhesion processes during the induction and maintenance phases of the immune response. In both groups, only patients responding to α-IFN therapy showed a marked decrease in serum ICAM-1 below baseline values.
Bronchial Hyperreactivity and Allergic Status in Inflammatory Bowel Disease
Authors: Ceyhan Berrin Bagcı , Karakurt Sait , Cevik Hikmet , Sungur Murat 
Published: April 2003

<i>Background:</i> Despite the known systemic manifestations of inflammatory bowel disease (IBD) and a large number of reports associating lung disease and IBD, the frequency of atopy and bronchial hyperreactivity (BHR) in IBD remains obscure. <i>Objectives:</i> The aim of this study was to investigate the prevalence of abnormal pulmonary function tests, BHR and the atopic status in patients with IBD. <i>Methods:</i> Thirty patients with IBD (19 with ulcerative colitis and 11 with Crohn’s disease; 19 male, 11 female) and 16 controls without any gastrointestinal disease (9 female, 7 male) were included. Patients were questioned with respect to pulmonary and allergic symptoms; subsequently, lung function tests, BHR, skin prick test positivity, peripheral eosinophilia and serum IgE levels were evaluated and compared with those of control subjects. <i>Results:</i> The mean duration of IBD was 5.3 ± 4.8 years. IBD patients had significantly more often respiratory symptoms in comparison with controls (odds ratio, OR: 9.0, p < 0.04). A previous diagnosis of asthma and antiasthmatic drug treatment were noted in 3/30 (10%) IBD patients. Allergic symptoms were more prevalent in IBD patients in comparison with the controls (OR: 13, p < 0.007), particularly in patients with ulcerative colitis (OR: 16, p < 0.004). The mean FEV<sub>1 </sub>was 3.1 ± 0.9 liters (96 ± 18% predicted), mean methacholine PD<sub>20</sub>: 14.7 ± 3.6 mg/ml, mean IgE: 190.5 ± 305.6 IU/ml (normal value <94 IU/ml) and the percentage of peripheral eosinophils was 3.1 ± 3.3% in the IBD patients. These values did not result in statistically significant differences in comparison with controls. Furthermore, abnormal lung function and BHR were observed in 8/30 (27%) and 5/30 (17%) IBD patients, respectively. Abnormal lung function tests were more prevalent in the IBD patients than in the controls (OR: 12, p < 0.04). Skin prick tests were positive in 15/30 (50%) IBD patients. The risk of a positive skin prick test increased in the IBD patients in comparison with the controls (OR: 7.0, p < 0.02). Duration and activity of IBD did not influence the prevalence of BHR, allergic and respiratory symptoms, abnormal lung function, high serum IgE levels and skin test positivity. <i>Conclusions:</i> Allergic symptoms, respiratory symptoms, abnormal lung function tests and skin prick test positivity were more common among the IBD patients in comparison with the controls.
Novel <i>NCCT </i>Gene Mutations as a Cause of Gitelman’s Syndrome and a Systematic Review of Mutant and Polymorphic <i>NCCT </i>Alleles
Authors: Reissinger Annette , Ludwig Michael , Utsch Boris , Prömse Astrid , Baulmann Johannes , Weisser Burkhard , Vetter Hans , Kramer Herbert J. , Bokemeyer Dirk 
Published: April 2003

<i>Background:</i> Gitelman’s syndrome (GS) is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria and these phenotypic features have been shown to be attributable to mutations in the gene encoding the thiazide-sensitive Na/Cl cotransporter <i>(NCCT). </i>Until now, 55 different mutations have been reported and most of the families affected with GS exhibit autosomal recessive inheritance. <i>Methods:</i> All 26 exons of the human <i>NCCT </i>gene were investigated in 2 German NCCT-deficient patients and their families. Mutation detection was performed by either direct automated sequencing of polymerase chain reaction (PCR)-amplified DNA products or by sequence analysis of cloned PCR products. <i>Results:</i> In a 47-year-old German GS female a novel non-conservative missense mutation (S314F) and a complex deletion/insertion in the <i>NCCT</i> gene were found to be associated with the disorder. A further novel non-conservative substitution (S402F) together with a frequently observed R209W exchange were found in a 19-year-old German GS female. <i>Conclusions:</i> The observation of a compound heterozygote state in both females affected and the absence of a GS phenotype in their relatives carrying a single mutant allele is consistent with an autosomal recessive pattern of inheritance.
Early Arterial Lactate and Prediction of Outcome in Preterm Neonates Admitted to a Neonatal Intensive Care Unit
Authors: Groenendaal Floris , Lindemans Caroline , Uiterwaal Cuno S.P.M. , de Vries Linda S. 
Published: April 2003

<i>Aim:</i> In the present study early arterial lactate samples were examined to predict adverse outcome in preterm neonates. <i>Subjects and Methods:</i> 88 preterm neonates (mean gestational age 29.8 weeks, mean birth weight 1,225 g) had arterial lactate levels measured from indwelling arterial catheters within the first 3 h of life. An adverse outcome was defined as death or abnormal neurodevelopment. The positive (PPV) and negative predictive value (NPV) of early arterial lactate levels for an adverse outcome (death or neurodevelopmental abnormalities) were calculated using receiver operating characteristic analysis. <i>Results:</i> PPV and NPV of arterial lactate within 3 h after birth were 0.47 and 0.92, respectively, with a cutoff value of 5.7 mmol/l. Umbilical blood gas values and 1 and 5 min Apgar scores had much lower PPVs. <i>Conclusion:</i> Arterial lactate levels within 3 h of life can be used to select preterm neonates who are at risk of an adverse outcome.
MRI-Directed Subthalamic Nucleus Surgery for Parkinson’s Disease
Authors: Patel Nikunj K. , Heywood Peter , O’Sullivan Karen , Love Seth , Gill Steven S. 
Published: April 2003

The subthalamic nucleus (STN) is now regarded as the optimal surgical target for the treatment of medically refractory idiopathic Parkinson’s disease. In our center, a predominantly MRI-directed method has been developed for targeting the STN. The STN is localized on T2-weighted images from a 1.5-T MRI scanner. Long acquisition, high-resolution images are acquired in both the axial and coronal planes under strict stereotactic conditions with the patient under general anesthesia. The boundary of STN is co-registered in both planes to give optimal 3-dimensional target definition. Stereotactic coordinates of the dorsolateral STN are recorded and the trajectory is planned down the axis of the nucleus in the coronal plane. Initially, per-operative macrostimulation was used for adjustment at the target prior to unilateral subthalamotomy in 26 patients. Five patients were lost to follow-up. Assessments of the lesions in post-operative images confirmed successful localisation of the lesions within the dorsolateral STN in all of the remaining 21 cases. In a subsequent series of 19 patients treated by deep brain stimulation (DBS), unilateral in 1 patient and bilateral in 18, the STN was targeted using the same MRI-directed method, guide tubes and radio-opaque stylettes were implanted, and target verification was entirely MRI-based. Following implantation of the guide tubes and stylettes, assessments of the per-operative MRI images for the 37 STN targetings confirmed a mean target error, between the stylette and the desired target in the axial plane, of 0.3 mm mediolaterally (SD = 0.4) and 0.4 mm anteroposteriorly (SD = 0.4), with median errors of 0.5 mm. This study demonstrates that MRI-directed targeting of the STN through guide tubes is accurate, and allows direct verification and corrections as necessary. Cumulative frequencies predict that the majority of DBS electrodes placed in this manner will be within 0.5 mm of the planned target. Because physiological methods are not required, the whole procedure can be performed under general anesthesia. We feel that planning with reference to a standard atlas is unreliable and not significantly helped by the addition of microelectrode recording, the accuracy of which in the axial plane is dependent upon the distance between the recording trajectories, which is typically 2 mm.
<i>Pseudomonas aeruginosa</i> Keratitis in IL-6-Deficient Mice
Authors: Cole Nerida , Bao Shisan , Stapleton Fiona , Thakur Archana , Husband Alan J. , Beagley Kenneth W. , Willcox Mark D.P. 
Published: April 2003

<i>Background:</i><i>Pseudomonas aeruginosa</i> infection is one of the most destructive diseases of the eye. The host response to this infection is critical to the outcome. Interleukin-6 (IL-6) is implicated in this response; however, the mechanisms by which IL-6 contributes to the host defences in corneal infection remain unclear. Using IL-6–/– mice, we have explored the role of IL-6 in <i>P. aeruginosa</i> keratitis. <i>Methods:</i> The eyes of IL-6 gene knockout and wild-type mice were challenged topically with <i>P. aeruginosa</i> and examined on days 1–7. Keratitis was examined clinically and histologically. Cytokine, chemokine and complement 3 levels were determined by ELISA and ICAM-1 by immunohistochemistry. <i>Results:</i> Clinically, the IL-6–/– mice showed more severe disease than wild-type mice and this was supported by the histological findings. More than 2-fold higher bacterial load was detected in the eyes of the IL-6–/– mice than in those of the wild-type mice. Neutrophil infiltration to the central cornea of the IL-6–/– mice failed to occur in response to infection, although a greater number of neutrophils were present in the whole eye. This may in part be due to the reduced expression of the adhesion molecule ICAM-1 in the cornea, but does not appear to stem from insufficient production of chemokines or complement 3. <i>Conclusions:</i> Our findings indicate that IL-6 is critical to the host defence of the cornea during <i>P. aeruginosa</i> infection. Pharmacological manipulation of the IL-6 response may represent a rational strategy for new interventions.
Comparison of the Effects of Cellulose Triacetate and Polysulfone Membrane on GPIIb/IIIa and Platelet Activation
Authors: Kuragano Takahiro , Kuno Tsutomu , Takahashi Yoshiko , Yamamoto Chii , Nagura Yuji , Takahashi Susumu , Kanmatsuse Katsuo 
Published: April 2003

<i>Background:</i> During hemodialysis session, several adverse reactions can occur on platelets, which are attributable to bioincompatibility of the dialysis membrane. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the receptor for fibrinogen, which mediates platelet aggregation and adhesion. Accordingly, we compared the influence of a cellulose triacetate (CTA) and polysulfone (PS) membrane on GPIIb/IIIa and platelet activation. <i>Methods:</i> Blood samples from 5 patients on hemodialysis were taken at 0 time, 15 min, 30 min, 60 min and 240 min, during a single hemodialysis session, by a crossover design using CTA or PS. Platelet count and plasma concentration of GPIIb/IIIa, β-thromboglobulin (β-TG) and platelet factor 4 (PF-4) were measured. GPIIb/IIIa was measured by flow cytometry. β-TG and PF-4 were measured by ELISA. <i>Results:</i> There was no significant change in the total amount of GPIIb/IIIa during dialysis session between the CTA and PS. However, the level of bound GPIIb/IIIa was significantly (p < 0.0002) increased from 1,426 ± 435 to 40,446 ± 2,777 mol/PLT with PS. In contrast, there was no significant change with CTA (3,258 ± 1,469 to 4,301 ± 1,422 mol/PLT). The platelet counts and β-TG and PF-4 behavior during the dialysis session did not show significant change between the PS and CTA. <i>Conclusion:</i> The characterization of changes in platelet membrane receptor (GPIIb/IIIa) may be a useful marker for studying the biocompatibility of dialysis membranes. On platelet aggregation, CTA might be more biocompatible membrane than PS.
Parathyroid Hormone Has a Prosclerotic Effect on Vascular Smooth Muscle Cells
Authors: Perkovic Vlado , Hewitson Timothy D. , Kelynack Kristen J. , Martic Marina , Tait Melanie G. , Becker Gavin J. 
Published: April 2003

Although accelerated atherosclerosis and arteriosclerosis are common in patients with renal failure, the pathogenesis of these changes is poorly understood. Parathyroid hormone (PTH) levels are elevated in renal failure, and have been linked to uraemic vascular changes in some studies. We examined the in vitro effects of increasing doses of the 1–34 fragment of PTH on human aortic vascular smooth muscle cells (VSMCs). Factors examined were: (1) collagen production using tritiated hydroxyproline incorporation and transcription of procollagen α<sub>1</sub>(I) mRNA; (2) change in the surface area of collagen I lattices; (3) mRNA transcription of the collagen binding protein β1 integrin; (4) proliferation using tritiated thymidine incorporation, and (5) methyl tetrazolium salt conversion to estimate live cell number after 5 days’ exposure to PTH. PTH at a concentration of 200 pmol/l increased total collagen synthesis (188 ± 25% of control, p < 0.01) as well as transcription of procollagen α<sub>1</sub>(I) mRNA (136 ± 11% of control, p < 0.005). PTH also increased reorganisation of collagen I lattices (surface area 47 ± 8% of well for control vs. 35.7 ± 2.5 and 34.3 ± 3.0% for PTH 100 and 200 pmol/l, respectively, p = 0.02) and upregulated β1 integrin mRNA expression (160 ± 20% of control at PTH concentration of 200 pmol/l, p < 0.05). PTH had no effect on VSMC proliferation or number at doses up to 200 pmol/l. In conclusion, PTH increases production and reorganisation of collagen by VSMCs in vitro. It is possible that more aggressive control of hyperparathyroidism in patients with renal failure may help to reduce the burden of cardiovascular disease in this patient population.