bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitazoxanide in the treatment of acquired immune deficiency syndrome‐related cryptosporidiosis: results of the United States compassionate use program in 365 patients
Authors: ROSSIGNOL J.‐F. 
Published: August 2006

SummaryBackgroundCryptosporidiosis in patients with acquired immune deficiency syndrome is a serious, life‐threatening disease.AimA large compassionate use clinical trial was conducted in the USA to make nitazoxanide available to patients with acquired immune deficiency syndrome‐related cryptosporidiosis and to collect data related to safety and effectiveness of the drug in this population.MethodsPatients at least 3 years of age with acquired immune deficiency syndrome, diarrhoea (≥4 stools/day for >2 weeks) and Cryptosporidium‐positive stools received 500–1500 mg of nitazoxanide twice daily. Patients were evaluated at weeks 1, 2, 4 and monthly thereafter for drug safety and effectiveness including the stool examinations, review of symptoms and patient diaries. Data analysis for clinical and parasitological response was intention‐to‐treat.ResultsThree hundred and sixty‐five patients were enrolled at 165 study centres throughout the USA. The duration of treatment ranged from 1 to 1528 days (median 62 days). Among the 357 patients included in the intent‐to‐treat analysis, 209 (59%) achieved a sustained clinical response while on treatment. Clinical responses were closely associated with Cryptosporidium‐negative stools (P < 0.0001). No safety issues were identified at doses up to 3000 mg/day or for long durations of treatment.ConclusionsNitazoxanide can be considered useful therapy for treatment of with acquired immune deficiency syndrome‐related cryptosporidiosis.
Meta‐analysis: the adjuvant role of granulocyte macrophage‐colony stimulating factor on immunological response to hepatitis B virus vaccine in end‐stage renal disease
Authors: FABRIZI F. , GANESHAN S. V. , DIXIT V. , MARTIN P. 
Published: August 2006

SummaryBackgroundChronic dialysis patients often fail to produce protective antibodies to hepatitis B virus surface antigen after vaccination towards hepatitis B virus (HBV). Several authors suggested a benefit for granulocyte macrophage‐colony stimulating factor (GM‐CSF) as an adjuvant to HBV vaccination in patients with end‐stage renal disease (ESRD). However, consistent information is still lacking.AimsTo evaluate efficacy and safety of GM‐CSF as adjuvant to hepatitis B vaccine in patients with ESRD by performing a systematic review with a meta‐analysis of prospective controlled clinical trials (CCTs).MethodsOnly trials comparing the seroresponse rate in study (GM‐CSF plus HBV vaccine) versus control (HBV vaccine alone) patients were included. We used the random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. The end‐point of interest was the rate of patients showing seroprotective anti‐hepatitis B titers at completion of HBV vaccine schedule in study versus control groups.ResultsWe identified seven studies involving 187 unique patients with ESRD. Only prospective CCTs were included. Pooling of study results showed a significant increase in response rates among study (GM‐CSF plus HBV vaccine) versus control (HBV vaccine alone) patients (pooled Odds Ratio, 4.63 [95% Confidence Intervals, 1.42; 15.14]). The P‐value was 0.02 for our test of study heterogeneity.ConclusionsOur meta‐analysis showed improved seroprotection rates with HBV vaccine after GM‐CSF administration.
Double‐blind, randomized, placebo‐controlled study to evaluate the effects of tegaserod on gastric motor, sensory and myoelectric function in healthy volunteers
Authors: TALLEY N. J. , CAMILLERI M. , BURTON D. , THOMFORDE G. , KOCH K. , RUCKER M. J. , PETERSON J. , ZINSMEISTER A. R. , EARNEST D. L. 
Published: August 2006

SummaryBackgroundThe effects of tegaserod on gastric accommodation and postprandial satiety remain unclear.AimTo compare the effects of tegaserod 6 mg twice daily vs. placebo on gastric volumes, postprandial symptoms, gastric emptying, small bowel transit and the surface electrogastrogram in female and male healthy volunteers.MethodsRandomized, double‐blind, placebo‐controlled study evaluated gastric function before and after 7 days of tegaserod 6 mg twice daily (n = 21) vs. placebo (n = 20) in healthy volunteers. Validated methods were used to study gastric emptying, myoelectrical activity, volumes and satiation postnutrient challenge.ResultsThere were no significant effects of tegaserod on the primary endpoints assessing gastric function: emptying of solids or liquids, total gastric volumes or myoelectrical activity. Maximum tolerated volume and aggregate symptom score with nutrient challenge on placebo were 1035 mL (±44) and 130 (±15) vs. 989 mL (±43) and 117 (±15) during tegaserod, respectively (all P = N.S.). Postprandial change in proximal gastric volume by single photon emission‐computed tomography was decreased in females on tegaserod (246 ± 30) vs. placebo (358 ± 32) (P = 0.015). Proximal fasting volumes in females were increased on tegaserod (126 ± 12) vs. placebo (92 ± 13) (P = 0.066).ConclusionsWhile tegaserod decreased proximal gastric volume change after a meal, it does not appear to have significant effects on gastric motor and sensory function in healthy individuals. Further studies are required in patients with disturbances of gastric motor and sensory function.
Omeprazole may be superior to famotidine in the management of iatrogenic ulcer after endoscopic mucosal resection: a prospective randomized controlled trial
Authors: YE B. D. , CHEON J. H. , CHOI K. D. , KIM S. G. , KIM J. S. , JUNG H. C. , SONG I. S. 
Published: August 2006

SummaryBackgroundAcid suppressing agents are widely used to treat the iatrogenic ulcers following endoscopic mucosal resection for gastric neoplasms. However, the relative merits of proton pump inhibitor or histamine2‐receptor antagonist for endoscopic mucosal resection‐induced ulcers are not known.AimTo prospectively compare omeprazole and famotidine for the healing of endoscopic mucosal resection‐induced ulcers and for bleeding control.MethodsAfter endoscopic mucosal resection, patients were randomly assigned to omeprazole (20 mg/day) or to famotidine (40 mg/day) group for a 28‐day treatment period. The ulcer sizes and stages, bleeding rates and ulcer‐related symptoms were compared.ResultsA total of 100 patients were randomized equally to each group. Forty‐one patients in each group were finally compared. The two groups were comparable in terms of baseline characteristics. Twenty‐eight days after treatment, the two groups were not different with respect to ulcer stage (P = 0.137) or ulcer reduction ratio (P = 0.380). No difference was observed with respect to ulcer‐related symptoms (P = 0.437) and no bleeding episode occurred in any of the 82 patients. In subgroup that underwent endoscopic submucosal dissection, fewer patients in the omeprazole group showed active ulcers than those in the famotidine group (P = 0.035).ConclusionOur results demonstrate that omeprazole may be superior to famotidine for iatrogenic ulcers following endoscopic mucosal resection, especially for large ulcers.
Three centuries of stomach symptoms in Scotland
Authors: BARON J. H. , WATSON F. , SONNENBERG A. 
Published: August 2006

SummaryBackgroundStomach pain and discomfort have been reported since antiquity.AimTo follow the time trends since the 18th century of dyspepsia, gastric ulcer, duodenal ulcer, and benign oesophageal disease to test when dyspepsia started to become a major clinical problem.MethodsThe annual in‐ and out‐patient records of the last three centuries from the Scottish Royal Infirmaries of Edinburgh, Aberdeen, Glasgow and Dundee were analysed. In addition, dispensary attendances, clinicians’ casebooks, students’ notebooks and medical texts have been scrutinized for historic statistics of upper gastrointestinal disease.ResultsDyspepsia was first recorded in the 1750s and increased markedly subsequently. Such dyspepsia persisted after gastric and duodenal ulcers appeared in the late 19th century and then declined again in the late 20th century. Non‐ulcer dyspepsia has remained the commonest diagnosis made after endoscopy for stomach pain in the beginning of the 21st century.ConclusionThe current commonest diagnosis of stomach pain, dyspepsia dates from the mid‐18th century. Any explanations of its causation need to consider this timing.
Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion
Authors: Fidler Meredith C. , Barshop Bruce A. , Gangoiti Jon A. , Deutsch Reena , Martin Michael , Schneider Jerry A. , Dohil Ranjan 
Published: August 2006

AimsAlthough cysteamine was first used in the treatment of cystinosis in 1976 and approved by the FDA as cysteamine bitartrate (Cystagon™) in 1994, surprisingly little pharmacological data are available for this compound. Cysteamine and its related drugs are currently being evaluated for the treatment of Huntington’s and Parkinson’s disease. The aim of te study was to understand the pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion.MethodCysteamine bitartrate was delivered through a naso‐enteric catheter into the stomach (n = 8), small intestine (n = 8) and caecum (n = 4) of normal subjects. Plasma cysteamine concentrations were determined using LC‐MS/MS.ResultsThe rate and extent of drug absorption were assessed by comparing AUC(0, ∞), Cmax and tmax, among the gastrointestinal infusion sites. Total cysteamine exposure, expressed as area under the curve (AUC(0, ∞)) was greatest when the drug was infused into the small intestine (4331.3 ± 1907.6 min × µm) followed by stomach (3901.9 ± 1591.9 min × µm) and caecum (3141.4 ± 1627.6 min × µm). Cysteamine infusion into the small intestine resulted in the most rapid rise to maximal plasma concentrations (tmax = 21 ± 0.56 min); tmax was delayed to 50 ± 26 min and 64 ± 26 min after gastric and caecal infusion, respectively. The maximum cysteamine plasma concentration (Cmax) was reached after infusion of the drug into the small intestine (51 ± 21 µm), which was higher than plasma Cmax concentrations after gastric (39 ± 16 µm) and caecal infusion (23 ± 15 µm).ConclusionsThe pharmacokinetic data generated help extend our understanding of cysteamine.
Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa‐2a (40KD) plus ribavirin
Authors: Snoeck Eric , Wade Janet R. , Duff Frank , Lamb Matthew , Jorga Karin 
Published: August 2006

AimTo assess the likelihood of a sustained virological response (SVR) vs. the likelihood of anaemia in patients with chronic hepatitis C.MethodsData from 1732 patients treated with peginterferon alfa‐2a (40KD) plus ribavirin in two randomized, multinational studies were pooled. Probabilities of SVR and anaemia were modelled using the generalized additive logistic model, with numerous clinical variables considered for entry into the model. Baseline haemoglobin was only considered in the analysis for anaemia.ResultsThe probability of anaemia increased from 6 to 16% as a function of the ribavirin dose kg−1 (12–16 mg kg−1), whereas the relationship between SVR and ribavirin dose kg−1 was influenced by hepatitis C virus (HCV) genotype. The probability of an SVR was not influenced by the ribavirin dose kg−1 in patients with HCV genotype 2 or 3 infection, but increased as a function of ribavirin dose kg−1 in patients with HCV genotype 1 infection (40–50% increase in probability of SVR for 12–16 mg kg−1 dose ribavirin increase). The probability of an SVR in patients included with HCV genotype 1 decreased with increasing HCV RNA level to about 3 million copies ml−1, but was relatively independent of increasing HCV RNA level thereafter. In addition, older age, a higher ribavirin apparent oral clearance and cirrhosis had a negative impact on achieving an SVR, but improved with increasing alanine aminotransferase (ALT) quotient. Sex and ribavirin dose kg−1 were the most important prognostic factors for anaemia, followed by baseline haemoglobin, age, baseline ALT quotient and cirrhosis.ConclusionThis study supports individualizing ribavirin dosages by HCV genotype and body weight, and highlights several clinical variables that influence the likelihood of an SVR compared with anaemia in chronic hepatitis C patients treated with peginterferon alfa‐2a (40KD) plus ribavirin.
Research Review: Family group decision‐making: a promising practice in need of more programme theory and research
Authors: Crampton David 
Published: August 2006

ABSTRACTThe use of family group decision‐making (FGDM) in child protection is rapidly increasing throughout the world. This paper provides a brief overview of the research evidence from 1996 to 2005 and proposes future directions for both practice and research. The purpose of the review is to help move the discussion of FGDM from a promising practice to an evidence‐based practice. The research review considers what is known about the child welfare outcomes of FGDM. The paper then turns to research concerning which families are offered FGDM and which FGDM processes appear to be important. The paper concludes with specific suggestions for developing FGDM programmes that can improve child protection practice and then testing these specific programmes in rigorous trials.
Both Fcγ and complement receptors mediate transfer of immune complexes from erythrocytes to human macrophages under physiological flow conditionsin vitro
Authors: Hepburn A L , Mason J C , Wang S , Shepherd C J , Florey O , Haskard D O , Davies K A 
Published: August 2006

SummaryAbnormal clearance by the mononuclear phagocytic system of immune complexes (IC) is important in the pathogenesis of systemic lupus erythematosus (SLE). We have developed an in vitro model to investigate the cellular mechanisms involved in the transfer of soluble IC from erythrocytes to human macrophages under physiological flow conditions. In this assay, erythrocytes bearing fluorescently labelled IC are perfused over monolayers of human monocytes or monocyte-derived macrophages in a parallel-plate flow chamber, and transfer quantified using confocal microscopy and flow cytometry. Using aggregated human IgG as a model IC, we have been able to demonstrate transfer of IC from erythrocytes to macrophages. Blocking studies with specific neutralizing antibodies have shown that both complement and Fcγ receptors are required for IC transfer. Blockade of CR4 (αxβ2 integrin), FcγRIIa or FcγRIII reduced transfer, while anti-CR3 (αmβ2 integrin) had no effect. Blockade of CR3, FcγRIIa or FcγRIII also reduced the number of adhesive interactions between fluorescently labelled IC-bearing erythrocytes and macrophage monolayers. Taken together with the transfer data, this suggests differing roles for these receptors in the human IC transfer reaction that includes an adhesive function which facilitates IC processing by mononuclear phagocytes. Finally, a functional effect of the FcγRIIa R131/H131 polymorphism, important in susceptibility to SLE, has also been demonstrated using this model. Uptake of IgG2 but not IgG1-containing soluble IC was reduced by macrophages from individuals homozygous for the R131 allelic variant of the receptor.
Longitudinal epitope analysis of insulin-binding antibodies in type 1 diabetes
Authors: Hall T R , Thomas J W , Padoa C J , Torn C , Landin-Olsson M , Ortqvist E , Hampe C S 
Published: August 2006

Summary
Autoantibodies to insulin (IAA) are one of the first markers of the autoimmune process leading to type 1 diabetes (T1D). While other autoantibodies in T1D have been studied extensively, relatively little is known about IAA and their binding specificities, especially after insulin treatment is initiated. We hypothesize that insulin antibodies (IA) that develop upon initiation of insulin treatment differ in their epitope specificities from IAA. We analysed insulin antibody binding specificities in longitudinal samples of T1D patients (n = 49). Samples were taken at clinical diagnosis of disease and after insulin treatment was initiated. The epitope specificities were analysed using recombinant Fab (rFab) derived from insulin-specific monoclonal antibodies AE9D6 and CG7C7. Binding of radiolabelled insulin by samples taken at onset of the disease was significantly reduced in the presence of rFab CG7C7 and AE9D6. rFab AE9D6 competed sera binding to insulin significantly better than rFab CG7C7 (P = 0·02). Binding to the AE9D6-defined epitope in the initial sample was correlated inversely with age at onset (P = 0·005). The binding to the AE9D6-defined epitope increased significantly (P &lt; 0·0001) after 3 months of insulin treatment. Binding to the CG7C7-defined epitope did not change during the analysed period of 12 months. We conclude that epitopes recognized by insulin binding antibodies can be identified using monoclonal insulin-specific rFab as competitors. Using this approach we observed that insulin treatment is accompanied by a change in epitope specificities in the emerging IA.
Agreement of anti-neutrophil cytoplasmic antibody measurements obtained from serum and plasma
Authors: Lee A S , Finkielman J D , Peikert T , Hummel A M , Viss M A , Jacob G L , Homburger H A , Specks U ,   Wegener’s Granulomatosis Etanercept Trial Research Group
Published: August 2006

Summary
Serum and plasma are used interchangeably to measure anti-neutrophil cytoplasmic antibodies (ANCA), even though the release of ANCA target antigens during the preparation of serum could affect ANCA assays and cause discrepancies between the results obtained from serum and plasma. To what extent ANCA test results obtained from serum agree and correlate with results from plasma remains unknown. Therefore, a comprehensive comparison was performed using serum and plasma samples which were collected in 175 patients with active Wegener's granulomatosis at enrolment of a recent randomized trial. These paired serum and plasma samples were subjected to parallel ANCA testing by standard indirect immunofluoresence on ethanol-fixed neutrophils, a direct enzyme-linked immunoassay (ELISA) for proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, and two different capture ELISAs for PR3-ANCA. The concordance of categorical serum and plasma ANCA results was assessed using κ-coefficients. These were &gt; 0·8 for all assays, indicating a very good concordance between positive and negative serum and plasma results. Spearman's correlation coefficients for serum and plasma PR3-ANCA values obtained by direct ELISA and both capture ELISAs were ≥ 0·95 (P &lt; 0·0001). Our study shows that serum and plasma samples can be used interchangeably for measuring ANCA.
Microclimatic factors associated with elevational changes in army ant density in tropical montane forest
Authors: O’DONNELL SEAN , KUMAR ANJALI 
Published: August 2006

Abstract1. The density (rate of encountering foraging raids) and species richness of army ants (Formicidae: Ecitoninae, and behaviourally convergent Ponerinae) was measured in montane tropical forest. Above‐ground and subterranean army ant raids were sampled using standard protocols at four sites across an elevational gradient (1200–1650 m above mean sea level) in and near cloud forest in the area of Monteverde, Costa Rica.2. Mean ambient temperature differed among sites, and decreased with elevation. For the above‐ground foraging army ant species, raid rates also declined with elevation. Surface army ant raid rates, however, were not affected by day to day weather variation within sites (temperature, cloud cover, or precipitation).3. For the underground foraging army ant species, raid rates did not vary directionally with elevation, and subterranean raid rates were not affected by day to day weather variation within sites.4. Army ant species richness was not directionally related to elevation, and species sharing among sites was generally high.5. Army ant community structure changes with elevation in Neotropical montane forest, and the results suggest that the strongest effects are of temperature regimes on the density of raids. These findings provide a baseline against which to detect changes in army ant communities that may accompany directional climate change in tropical cloud forests.
How do temperature, dissolved organic matter and nutrients influence the response of Leptodiaptomus ashlandi to UV radiation in a subalpine lake?
Authors: COOKE SANDRA L. , WILLIAMSON CRAIG E. , SAROS JASMINE E. 
Published: August 2006

Summary1. Ultraviolet radiation (UV) is an important stressor for zooplankton in alpine lake ecosystems. Multiple environmental variables such as dissolved organic matter (DOM), temperature and nutrient availability may alter how UV affects zooplankton.2. We conducted a week‐long experiment manipulating UV, nutrients and DOM in enclosures suspended at the surface of cold and warm alpine lakes to determine the interactive effects of these variables on ovigerous Leptodiaptomus ashlandi (Marsh, 1893), a calanoid copepod.3. UV had a negative effect on nauplii and gravid females at the colder temperature and at low, ambient DOM levels, but had no effect at the warmer temperature or when DOM was added. At the warmer temperature, fewer nauplii were produced in the +nutrient compared to −nutrient treatment. Adult survival was not affected by UV or any other experimental variable.4. These results demonstrate that the extent of the impact of UV radiation on zooplankton in alpine systems is altered by other environmental variables, and that these effects may not be apparent from experiments that look only at the survival of adult organisms that are better defended against UV.
Distinct roles of Ca2+mobilization and G protein usage on regulation of Toll‐like receptor function in human and murine mast cells
Authors: Zaidi Asifa K. , Thangam Elden Retna Raj B. , Ali Hydar 
Published: August 2006

SummaryToll‐like receptors (TLRs) expressed in mast cells play important roles in orchestrating host defence against bacterial pathogens. Previous studies demonstrated that TLR2 agonist tripalmitoyl‐S‐glycero‐Cys‐(Lys)4(Pam3Cys) stimulates both degranulation and cytokine production in human mast cells but only induces cytokine production in murine mast cells. To determine the molecular basis for this difference, we utilized a human mast cell line LAD 2, murine lung and bone marrow‐derived mast cells (MLMC and BMMC). We found that Pam3Cys caused a sustained Ca2+mobilization and degranulation in LAD 2 mast cells but not in MLMC or BMMC. Despite these differences, Pam3Cys stimulated equivalent chemokine CCL2 generation in all mast cell types tested. Cyclosporin A (CsA), an inhibitor of Ca2+/calcineurin‐mediated nuclear factor of activated T cells (NFAT) activation, blocked chemokine production in LAD 2 but not in MLMC or BMMC. In contrast, inhibitors of nuclear factor kappa B (NF‐κB) completely blocked CCL2 production in MLMC and BMMC but not in LAD 2 mast cells. Pertussis toxin and U0126, which, respectively, inhibit Gαi,extracellular signal‐regulated kinase (ERK) phosphorylation substantially inhibited Pam3Cys‐induced CCL2 generation in LAD 2 mast cells but had little or no effect on chemokine generation in MLMC and BMMC. These findings suggest that TLR2 activation in human LAD 2 mast cells and MLMC/BMMC promotes the release of different classes of mediators via distinct signalling pathways that depend on Ca2+mobilization and G protein usage.
Gastric Dilatation–volvulus as Complication after Surgical Removal of a Splenic Haemangiosarcoma in a Dog
Authors: Marconato L. 
Published: August 2006

SummaryAn 8‐year‐old crossbreed dog presented after one episode of acute collapse due to rupture of a splenic haemangiosarcoma. Following splenectomy the dog recovered well. Two days after discharge the dog re‐presented because of gastric dilatation–volvulus (GDV) that eventually led to his death. Splenectomy to remove a voluminous splenic tumour may predispose to GDV and dogs may benefit from concurrent prophylactic gastropexy.