bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myelosuppression monitoring after immunomodulator initiation in veterans with inflammatory bowel disease: a national practice audit
Authors: Hou J. K. , Kramer J. R. , Richardson P. , Sansgiry S. , El‐Serag H. B. 
Published: October 2012

SummaryBackgroundImmunomodulator medications (IMM) play a vital role in the care of patients with inflammatory bowel disease (IBD). IBD practice guidelines recommend myelosuppression monitoring after initiation of IMM.AimTo identify adherence rates and predictors of myelosuppression monitoring after IMM initiation in a large practice setting.MethodsWe identified a national cohort of VA users with IBD for the fiscal years 2003–2009 using the Veterans Affairs administrative datasets. Subjects with filled prescriptions for IMM were included. The primary endpoint was the proportion of subjects who had a white blood cell (WBC) test completed within 90 days of the IMM index date. Determinants of myelosuppression monitoring were identified by univariate and multivariate analyses.ResultsA total of 6045 unique IBD patients were identified with filled IMM prescriptions. Overall, only 57% of subjects completed a WBC test within 90 days of IMM index date. Monitoring rates increased over time, from 48% in 2003 to 75% in 2009. There was variability of monitoring rates by facility, ranging from 0 to 83%. In multivariate analyses, older age at IMM index date was associated with a lower rate of monitoring. Frequency of VA encounters and IMM index date were associated with increased rates of myelosuppression monitoring.ConclusionsMonitoring for myelosuppression among veterans with inflammatory bowel disease after immunomodulator medications initiation is low with wide variability based on facility. This may reflect a low quality of care among veterans with IBD. Provider‐ and system‐wide interventions are needed to improve adherence and reduce variability of immunomodulator medications monitoring across facilities.
Does co‐treatment with immunosuppressors improve outcome in patients with Crohn's disease treated with adalimumab?
Authors: Reenaers C. , Louis E. , Belaiche J. , Seidel L. , Keshav S. , Travis S. 
Published: October 2012

SummaryBackgroundThere is clear benefit from combination therapy with infliximab and immunosuppressive drugs (IS), but few data are available for adalimumab (ADA).AimTo assess the efficacy of ADA monotherapy and ADA+IS for induction and maintenance therapy in Crohn's disease.MethodsRetrospective study of patients with Crohn's disease treated with ADA in Oxford, UK or Liège, Belgium. Treatment periods were divided into 6‐month semesters. A combination therapy semester was defined as ADA+IS for at least 3 months; successful induction meant clinical response; a semester with flare as ADA dose escalation, starting steroids, perianal complication, or surgery; and ADA failure as ADA withdrawal for secondary loss of response or intolerance. Semesters with and without flares were compared through univariate and multivariate analysis.ResultsSuccessful induction was achieved in 171/207 (83%) patients, with no significant difference between ADA+IS and ADA monotherapy (85% vs. 82%, P = 0.50). Five hundred and sixty‐two semesters in 181 patients were included for maintenance analysis. ADA+IS was not associated with fewer semesters with flare (34% vs. 35%, P = 0.96), or with ADA failure (6% vs. 8%, P = 0.43). Nevertheless, combination therapy in the first semester was associated with a lower risk of ADA failure (5% vs. 10%, P = 0.04, OR = 0.48) and combination therapy beyond 6 months was associated with fewer semesters with flares (14% vs. 36%, P = 0.02, OR = 0.31).ConclusionsThere may be a benefit from adalimumab+immunosuppressive drugs combination therapy during the first semester of initiating adalimumab, with a slight decrease in adalimumab failure and lower need for adalimumab dosage escalation.
Predicting post‐traumatic stress disorder following first onset acute coronary syndrome: Testing a theoretical model
Authors: Marke Victoria , Bennett Paul 
Published: October 2012

ObjectivesThis research identified which theoretically predicted factors (Joseph, Williams, & Yule, 1997) were associated with the severity of post‐traumatic stress disorder (PTSD) symptoms 1 and 6 months following onset of acute coronary syndrome (ACS). Predictor variables included event factors, peri‐traumatic distress; and maintaining factors including coping strategies, social support, re‐appraisal of event threat, and beliefs about the nature of ACS. Associations with alexithymia were also explored.MethodOne hundred and fifty participants completed questionnaires in hospital and at 1‐ and 6‐month follow‐up.ResultsHierarchical multiple regression including both baseline and contemporaneous variables explained 52 and 42% of the variance in PTSD symptoms at each follow‐up. At 1‐month follow‐up, predictors of PTSD symptoms were as follows: peri‐traumatic distress, concern over symptoms, illness comprehension, and lack of social support. At 6‐month follow‐up, predictors were: peri‐traumatic distress, lack of social support, use of problem‐focused coping, and continued symptoms.ConclusionsThe Joseph et al. model was generally supported. The data allow some degree of prediction of high risk individuals and suggest some possible interventions.
Clinical phenotype, laboratory features and genotype of 35 patients with heritable dysfibrinogenaemia
Authors: Shapiro Susan E. , Phillips Emma , Manning Richard A. , Morse Colin V. , Murden Sherina L. , Laffan Michael A. , Mumford Andrew D. 
Published: October 2012

SummaryHeritable dysfibrinogenaemia (HD) is a rare qualitative disorder of fibrinogen (FGN). To better describe the clinical, laboratory and genotypic spectrum of HD, we evaluated 35 subjects identified at two UK centres using laboratory criteria. 12/35(34%) subjects with HD experienced bleeding (bleeding score >1 at any site), 3/35(9%) thrombosis and 20/35(57%) were asymptomatic. Amongst subjects with bleeding, symptoms were typically mild, at one anatomical site and seldom occurred after invasive procedures. All subject showed dry clot weight within or above laboratory reference interval (median 3·2 g/l; range 1·9–5·1), reduced Clauss fibrinogen (median 0·52 g/l; range 0·21–1·3), and prolonged thrombin (median 30·7 s; range 21·3–45·7) and reptilase (median 42·0 s; range 20·0–68·0) times. In all subjects, the prothrombin time ratio (PTR), determined by Sysmex CA‐1500 coagulometer and Innovin activator, was abnormal (median 1·42; range 1·22–1·61). The activated partial thromboplastin time ratio and PTR with other coagulometers and activators were comparatively insensitive to HD. All subjects with HD harboured heterozygous candidate nucleotide variations within known hotspots in the FGN genes. The HD variants identified in this cross‐sectional study seldom have significant clinical manifestations and show similar laboratory features irrespective of genotype. Selection of coagulometer and PT activator may markedly affect the detection of new HD cases using coagulation screening tests.
Investigating Mammalian Tyrosine Phosphatase Inhibitors as Potential ‘Piggyback’ Leads to Target Trypanosoma brucei Transmission
Authors: Ruberto Irene , Szoor Balazs , Clark Rachel , Matthews Keith R. 
Published: October 2012

African trypanosomiasis is a neglected tropical disease affecting humans and animals across 36 sub‐Saharan African countries. We have investigated the potential to exploit a ‘piggyback’ approach to inhibit Trypanosoma brucei transmission by targeting the key developmental regulator of transmission, T. brucei protein tyrosine phosphatase 1. This strategy took advantage of the extensive investment in inhibitors for human protein tyrosine phosphatase 1B, a key target for pharmaceutical companies for the treatment of obesity and diabetes. Structural predictions for human and trypanosome tyrosine phosphatases revealed the overall conservation of important functional motifs, validating the potential for exploiting cross specific compounds. Thereafter, nineteen inhibitors were evaluated; seventeen from a protein tyrosine phosphatase 1B‐targeted inhibitor library and two from literature analysis – oleanolic acid and suramin, the latter of which is a front line drug against African trypanosomiasis. The compounds tested displayed similar inhibitory activities against the human and trypanosome enzymes, mostly behaving as noncompetitive inhibitors. However, their activity against T. brucei in culture was low, necessitating further chemical modification to improve their efficacy and specificity. Nonetheless, the results validate the potential to explore a ‘piggyback’ strategy targeting T. brucei protein tyrosine phosphatase 1 through exploiting the large pharmacological investment in therapies for obesity targeting protein tyrosine phosphatase 1B.
Effects of geohelminth infection and age on the associations between allergen‐specific IgE, skin test reactivity and wheeze: a case‐control study
Authors: Moncayo A.‐L. , Vaca M. , Oviedo G. , Workman L. J. , Chico M. E. , Platts‐Mills T. A. E. , Rodrigues L. C. , Barreto M. L. , Cooper P. J. 
Published: October 2012

SummaryBackgroundMost childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age.ObjectiveTo explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze.MethodsA case‐control study was done in 376 subjects (149 cases and 227 controls) aged 7–19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross‐sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen‐specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti‐Ascaris IgE in plasma.ResultsThe fraction of recent wheeze attributable to anti‐Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti‐Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33–3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49–11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections.Conclusions and clinical relevanceAtopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti‐Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.
T cell depletion in paediatric stem cell transplantation
Authors: Booth C , Veys P 
Published: October 2012

Summary
Haematopoietic stem cell transplantation (HSCT) can be a curative procedure for a growing number of paediatric diseases, but as the indications for HSCT grow, so does the need to find suitable stem cell donors. When the preferred option of a genoidentical sibling donor is not available alternative donors, including unrelated adult or umbilical cord blood donors, or haploidentical related donors may be considered. Outcome following alternative donor HSCT has improved over the past 20 years but graft-versus-host disease (GvHD) remains a significant obstacle. T cell depletion (TCD) for non-genoidentical grafts aims to reduce the morbidity and mortality associated with GvHD, but this intervention has not led directly to improved survival due to delayed immune reconstitution and increased infections, graft rejection and increased rates of disease relapse. Limited data from the paediatric population, however, suggest some encouraging results for children undergoing haploidentical HSCT: a move from positive selection of CD34+ haematopoietic stem cells towards negative depletion of specific cell subsets in order to retain useful accessory cells within the graft appears to enhance immune reconstitution and improve disease-free survival. Here we review recent paediatric outcome data for T cell-depleted HSCT, explore the role of serotherapy in conditioning regimens and look at future possibilities to improve outcome, including novel allodepletion techniques, suicide gene therapy and pathogen-specific immunotherapy.
Volume interpolated 3D‐spoiled gradient echo sequence is better than dynamic contrast spin echo sequence for MRI detection of corticotropin secreting pituitary microadenomas
Authors: Kasaliwal Rajeev , Sankhe Shilpa S. , Lila Anurag R. , Budyal Sweta R. , Jagtap Varsha S. , Sarathi Vijaya , Kakade Harshal , Bandgar Tushar , Menon Padmavathy S. , Shah Nalini S. 
Published: October 2012

SummaryBackgroundVarious techniques have been attempted to increase the yield of magnetic resonance imaging (MRI) for localization of pituitary microadenomas in corticotropin (ACTH)‐dependent Cushing's syndrome (CS).ObjectiveTo compare the performance of dynamic contrast spin echo (DC‐SE) and volume interpolated 3D‐spoiled gradient echo (VI‐SGE) MR sequences in the diagnostic evaluation of ACTH‐dependent CS.DesignData was analysed retrospectively from a series of ACTH‐dependent CS patients treated over 2‐year period at a tertiary care referral centre (2009–2011).PatientsThirty‐six patients (24 female and 12 male) were diagnosed to have ACTH‐dependent CS during the study period. All patients underwent MRI by both sequences during a single examination. Cases with negative and equivocal pituitary MR imaging underwent corticotropin‐releasing hormone (CRH) stimulated bilateral inferior petrosal sinus sampling (BIPSS) to confirm pituitary origin of ACTH excess state. Thirty patients were finally diagnosed to have Cushing's disease (CD) [based on histopathology proof of adenoma and/or remission (partial/complete) of hypercortisolism postsurgery]. Six patients were diagnosed to have histopathologically proven ectopic CS.ResultsOf 30 patients with CD, 24 patients had microadenomas and 6 patients had macroadenomas. DC‐SE MRI sequence was able to identify microadenomas in 16 of 24 patients, whereas postcontrast VI‐SGE sequence was able to identify microadenomas in 21 of 24 patients. All six patients of ectopic CS had negative pituitary MR imaging by both techniques (specificity: 100%).ConclusionVI‐SGE MR sequence was better for localization of pituitary microadenomas particularly when DC‐SE MR sequence is negative or equivocal and should be used in addition to DC‐SE MR sequence for the evaluation of ACTH‐dependent CS.
Variable magnitude of drug interaction between oral voriconazole and cyclosporine A in recipients of allogeneic hematopoietic stem cell transplantation
Authors: Kikuchi Taku , Mori Takehiko , Yamane Akiko , Kato Jun , Kohashi Sumiko , Okamoto Shinichiro 
Published: October 2012

AbstractDrug interaction between voriconazole and calcineurin inhibitors is often problematic after allogeneic hematopoietic stem cell transplantation (HSCT) or solid organ transplantation. We previously demonstrated an unpredictable inter‐individual variability in the magnitude of this drug interaction; however, the route of drug administration was not taken into account. In this study, the drug interaction between voriconazole and calcineurin inhibitors was further analyzed under the condition that both agents were administered orally. Twenty adult recipients of HSCT who had already been on a steady dose of oral cyclosporine A (CsA) and were started on oral voriconazole (400 mg/d) were eligible. The changes in the concentration/dose (C/D) ratio of CsA were evaluated by comparing the trough concentrations of CsA measured before and 7–10 d after initiating voriconazole. The median C/D ratio of CsA increased significantly from 64.1 to 114.3 (ng/mL)/(mg/kg) after initiating voriconazole (p < 0.01), and the median increase was 83.0% (range, 0.3–224.7%). The plasma concentration of voriconazole did not correlate significantly with the increase of the C/D ratio (ρ = −0.18, p = 0.45). These results indicate that the magnitude of drug interaction between oral voriconazole and CsA is widely variable, and it could not be explained by the difference in the blood levels of voriconazole. Further studies are required to elucidate the mechanism for this variability.
Relevance of HLA compatibility in living donor liver transplantation: the double‐edged sword associated with the patient outcome
Authors: Uchiyama Hideaki , Kayashima Hiroto , Matono Rumi , Shirabe Ken , Yoshizumi Tomoharu , Ikegami Toru , Soejima Yuji , Matsuura Toshiharu , Taguchi Tomoaki , Maehara Yoshihiko 
Published: October 2012

AbstractHLA compatibility in living donor liver transplantation (LDLT) seems relevant to the acceptability of graft livers because LDLT recipients often share most or some part of HLAs with the respective donors. This study retrospectively investigated whether HLA compatibility affected the outcome of LDLT. Three hundred ninety LDLTs were performed in this hospital, and 346 pairs of HLAs (HLA‐A, B, DR) were retrieved from the medical record between October 1996 and March 2011. The dates of the deaths were censored when a recipient apparently died of or was retransplanted by other causes than graft failure because of host‐versus‐graft (HVG) response to purely analyze the outcomes of LDLT in view of HVG response. The relationship between HLA compatibility and graft‐versus‐host disease (GVHD) was also analyzed. No recipients with recipient‐against‐donor HLA mismatch (R→D MM) 0 experienced graft failure by HVG response. On the other hand, three of five recipients with “R→D MM 0” together with “donor‐against‐recipient MM 3” died of fatal GVHD. HLA compatibility in LDLT not only affected the long‐term acceptance of graft livers but also the risk of fatal GVHD.
Delayed graft function requiring more than one‐time dialysis treatment is associated with inferior clinical outcomes
Authors: Jayaram Deepa , Kommareddi Mallika , Sung Randall S. , Luan Fu L. 
Published: October 2012

AbstractDelayed graft function (DGF) is a common complication of deceased donor kidney transplantation with negative impact on clinical outcomes. In a single‐center retrospective analysis, we compared patient and kidney survival, early renal function, and the incidence of acute rejection during the first year among all adult deceased donor kidney transplant patients without DGF, with DGF requiring one‐time and/or more than one‐time dialysis treatment between January 1, 2000, and December 31, 2008. Of 831 adult kidney transplant patients, 74 (8.9%) required one‐time and 134 (16.1%) more than one‐time dialysis treatment post‐transplantation, respectively. While DGF patients with one‐time dialysis treatment had comparable clinical outcomes to that of patients without DGF, patients with DGF requiring more than one‐time dialysis treatment had a 45% increased risk for death (HR 1.45, 95% CI 1.02, 2.05, p = 0.04) after adjustment for the differences in demographic and baseline characteristics. Furthermore, DGF patients with more than one‐time dialysis requirement displayed significantly lower renal function after recovery (OR 0.32, 95% CI 0.21, 0.49, p < 0.001, for eGFR ≥ 60 mL/min) and higher incidence of acute rejection during the first year (OR 1.66, 95% CI 1.11, 2.49, p = 0.015). Additional studies of therapeutic approaches to manage patients with prolonged DGF are needed.
Effects of rifampin and mefenamic acid on the pharmacokinetics and pharmacodynamics of dapagliflozin
Authors: Kasichayanula S. , Liu X. , Griffen S. C. , LaCreta F. P. , Boulton D. W. 
Published: October 2012

AimsDapagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that decreases serum glucose by reducing renal glucose reabsorption, thereby promoting urinary glucose excretion. Dapagliflozin is primarily metabolized via the uridine diphosphate‐glucuronosyltransferase (UGT)1A9 pathway to its major inactive metabolite, dapagliflozin 3‐O‐glucuronide. The aim of this study was to evaluate the potential for drug‐drug interaction between dapagliflozin and two potential UGT1A9 modulators.MethodsThe results of two open‐label, non‐randomized, single‐sequence studies are reported in which the effects of rifampin (a pleiotropic drug‐metabolizing enzyme inducer; study 1) and mefenamic acid (a strong UGT1A9 inhibitor; study 2) were evaluated on the pharmacokinetics and pharmacodynamics (assessed by urinary glucose excretion [UGE]) of dapagliflozin in healthy subjects. In study 1, 14 subjects received single doses of dapagliflozin 10 mg alone and in the presence of rifampin 600 mg QD (6 days). In study 2, 16 subjects received single doses of dapagliflozin 10 mg alone and in the presence of mefenamic acid 250 mg q6h (5 days).ResultsRifampin reduced total exposure (area under the concentration‐time curve from time 0 to infinity [AUC0‐inf]) to dapagliflozin by 22% and mefenamic acid increased dapagliflozin AUC0‐inf by 51%. No clinically meaningful effect of rifampin or mefenamic acid on the pharmacokinetics of dapagliflozin or on dapagliflozin‐mediated urinary glucose excretion was observed.ConclusionModest changes in dapagliflozin exposure were seen with rifampin and mefenamic acid with minor changes in UGE, none of which were considered clinically meaningful.
A novel mutation in the albumin gene (c.1A>C) resulting in analbuminemia
Authors: Caridi Gianluca , Dagnino Monica , Lugani Francesca , Shalev Stavit A. , Campagnoli Monica , Galliano Monica , Spiegel Ronen , Minchiotti Lorenzo 
Published: October 2012

Eur J Clin Invest 2012AbstractBackground  Analbuminemia (OMIM # 103600) is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. The trait is caused by a variety of mutations within the albumin gene.Design  We report here the clinical and molecular characterisation of two new cases of congenital analbuminemia diagnosed in two members of the Druze population living in a Galilean village (Northern Israel) on the basis of their low level of circulating albumin. The albumin gene was screened by single‐strand conformation polymorphism and heteroduplex analysis, and the mutated region was submitted to DNA sequencing.Results  Both the analbuminemic subjects resulted homozygous for a previously unreported c.1 A>C transversion, for which we suggest the name Afula from the hospital where the two cases were investigated. This mutation causes the loss of the primary start codon ATG for Met1, which is replaced by a – then untranslated – triplet CTG for Leu. (p.Met1Leu). The use of an alternative downstream ATG codon would probably give rise to a completely aberrant polypeptide chain, leading to a misrouted intracellular transport and a premature degradation.Conclusions  The discovery of this new ALB mutation, probably inherited from a common ancestor, sheds light on the molecular mechanism underlying the analbuminemic trait and may serve in the development of a rapid genetic test for the identification of a‐symptomatic heterozygous carriers in the Druze population in the Galilee.