tbuckley/cabot-search huggingface dataset:
Phase I/II Study of Atrasentan, an Endothelin A Receptor Antagonist, in Combination with Paclitaxel and Carboplatin as First-Line Therapy in Advanced Non–Small Cell Lung Cancer
Authors: Alberto A. Chiappori, Eric Haura, Francisco A. Rodriguez, David Boulware, Rachna Kapoor, Anthony M. Neuger, Richard Lush, Barbara Padilla, Michelle Burton, Charles Williams, George Simon, Scott Antonia, Daniel M. Sullivan, Gerold Bepler
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Endothelins and their cell membrane receptors (ETAR and ETBR) are implicated in neoplastic pathogenesis. Atrasentan, a potent, selective ETAR antagonist, has a direct effect on tumor proliferation, apoptosis, and angiogenesis. This study was designed to assess the influence of atrasentan on paclitaxel pharmacokinetics and to determine the safety and efficacy of atrasentan in combination with paclitaxel-carboplatin. Experimental Design: Chemonaive patients with stage IIIB (malignant pleural effusion) and IV non–small cell lung cancer were enrolled. Toxicity and response were determined using the National Cancer Institute Common Toxicity Criteria version 2.0 and Response Evaluation Criteria in Solid Tumors criteria, respectively. Treatment consisted of paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6) administered on day 1 every 3 weeks. A fixed 10 mg daily oral dose of atrasentan was administered continuously, starting on day 4 of cycle 1. Paclitaxel clearance was calculated during the first two cycles (pre- and post-atrasentan) in the first 10 patients. Results: All 44 patients were evaluable for survival, toxicity, and response. No significant change in mean paclitaxel clearance was detected (mean ± SD, 21.2 ± 4.5 L/h versus 21.3 ± 4.9 L/h) for pre- and post-atrasentan values, respectively (P = 0.434). Grade 3/4 toxicities ≥10% were lymphopenia (22.7%), neutropenia (20.5%), dyspnea (11.4%), and hyperglycemia (11.4%). Response rate was 18.2%, with progression-free survival of 4.2 months, median survival of 10.6 months, and 1-year survival of 43%. Conclusion: Atrasentan plus paclitaxel-carboplatin was safe and well tolerated, with no apparent paclitaxel-atrasentan pharmacokinetic interaction. Efficacy and survival in advanced non–small cell lung cancer were comparable with studies of chemotherapy alone.
A Predominantly Clonal Multi-Institutional Outbreak of<i>Clostridium difficile</i>–Associated Diarrhea with High Morbidity and Mortality
Authors: Vivian G. Loo, Louise Poirier, Mark A. Miller, Matthew Oughton, Michael D. Libman, Sophie Michaud, Anne-Marie Bourgault, Tuyen Nguyen, Charles Frenette, Mirabelle Kelly, Anne Vibien, Paul Brassard, Susan Fenn, Ken Dewar, Thomas J. Hudson, Ruth Horn, Pierre René, Yury Monczak, André Dascal
Journal: New England Journal of Medicine (2005)

In March 2003, several hospitals in Quebec, Canada, noted a marked increase in the incidence of Clostridium difficile-associated diarrhea.In 2004 we conducted a prospective study at 12 Quebec hospitals to determine the incidence of nosocomial C. difficile-associated diarrhea and its complications and a case-control study to identify risk factors for the disease. Isolates of C. difficile were typed by pulsed-field gel electrophoresis and analyzed for binary toxin genes and partial deletions in the toxin A and B repressor gene tcdC. Antimicrobial susceptibility was evaluated in a subgroup of isolates.A total of 1703 patients with 1719 episodes of nosocomial C. difficile-associated diarrhea were identified. The incidence was 22.5 per 1000 admissions. The 30-day attributable mortality rate was 6.9 percent. Case patients were more likely than matched controls to have received fluoroquinolones (odds ratio, 3.9; 95 percent confidence interval, 2.3 to 6.6) or cephalosporins (odds ratio, 3.8; 95 percent confidence interval, 2.2 to 6.6). A predominant strain, resistant to fluoroquinolones, was found in 129 of 157 isolates (82.2 percent), and the binary toxin genes and partial deletions in the tcdC gene were present in 132 isolates (84.1 percent).A strain of C. difficile that was resistant to fluoroquinolones and had binary toxin and a partial deletion of the tcdC gene was responsible for this outbreak of C. difficile-associated diarrhea. Exposure to fluoroquinolones or cephalosporins was a risk factor.
Atypical Antipsychotic Augmentation in Major Depressive Disorder: A Meta-Analysis of Placebo-Controlled Randomized Trials
Authors: J. Craig Nelson, George I. Papakostas
Journal: American Journal of Psychiatry (2009)

The authors sought to determine by meta-analysis the efficacy and tolerability of adjunctive atypical antipsychotic agents in major depressive disorder.Searches were conducted of MEDLINE/PubMed (1966 to January 2009), the Cochrane database, abstracts of major psychiatric meetings since 2000, and online trial registries. Manufacturers of atypical antipsychotic agents without online registries were contacted. Trials selected were acute-phase, parallel-group, double-blind controlled trials with random assignment to adjunctive atypical antipsychotic or placebo. Patients had nonpsychotic unipolar major depressive disorder that was resistant to prior antidepressant treatment. Response, remission, and discontinuation rates were either reported or obtained. Data were extracted by one author and checked by the second. Data included study design, number of patients, patient characteristics, methods of establishing treatment resistance, drug doses, duration of the adjunctive trial, depression scale used, response and remission rates, and discontinuation rates for any reason or for adverse events.Sixteen trials with 3,480 patients were pooled using a fixed-effects meta-analysis. Adjunctive atypical antipsychotics were significantly more effective than placebo (response: odds ratio=1.69, 95% CI=1.46-1.95, z=7.00, N=16, p<0.00001; remission: odds ratio=2.00, 95% CI=1.69-2.37, z=8.03, N=16, p<0.00001). Mean odds ratios did not differ among the atypical agents and were not affected by trial duration or method of establishing treatment resistance. Discontinuation rates for adverse events were higher for atypical agents than for placebo (odds ratio=3.91, 95% CI=2.68-5.72, z=7.05, N=15, p<0.00001).Atypical antipsychotics are effective augmentation agents in major depressive disorder but are associated with an increased risk of discontinuation due to adverse events.
A flippase-independent function of ATP8B1, the protein affected in familial intrahepatic cholestasis type 1, is required for apical protein expression and microvillus formation in polarized epithelial cells
Authors: Patricia M. Verhulst, Lieke M. van der Velden, Viola Oorschot, Ernst E. van Faassen, Judith Klumperman, Roderick H.J. Houwen, Thomas G. Pomorski, Joost C.M. Holthuis, Leo W.J. Klomp
Journal: Hepatology (2010)

Mutations in ATP8B1 cause familial intrahepatic cholestasis type 1, a spectrum of disorders characterized by intrahepatic cholestasis, reduced growth, deafness, and diarrhea. ATP8B1 belongs to the P4 P-type adenosine triphosphatase (ATPase) family of putative aminophospholipid translocases, and loss of aminophospholipid asymmetry in the canalicular membranes of ATP8B1-deficient liver cells has been proposed as the primary cause of impaired bile salt excretion. To explore the origin of the hepatic and extrahepatic symptoms associated with ATP8B1 deficiency, we investigated the impact of ATP8B1 depletion on the domain-specific aminophospholipid translocase activities and polarized organization of polarized epithelial Caco-2 cells. Caco-2 cells were stably transfected with short hairpin RNA constructs to block ATP8B1 expression. Aminophospholipid translocase activity was assessed using spin-labeled phospholipids. The polarized organization of these cells was determined by pulse-chase analysis, cell-fractionation, immunocytochemistry, and transmission electron microscopy. ATP8B1 was abundantly expressed in the apical membrane of Caco-2 cells, and its expression was markedly induced during differentiation and polarization. Blocking ATP8B1 expression by RNA interference (RNAi) affected neither aminophospholipid transport nor the asymmetrical distribution of aminophospholipids across the apical bilayer. Nonetheless, ATP8B1-depleted Caco-2 cells displayed profound perturbations in apical membrane organization, including a disorganized apical actin cytoskeleton, a loss in microvilli, and a posttranscriptional defect in apical protein expression. Conclusion: Our findings point to a critical role of ATP8B1 in apical membrane organization that is unrelated to its presumed aminophospholipid translocase activity, yet potentially relevant for the development of cholestasis and the manifestation of extrahepatic features associated with ATP8B1 deficiency. (Hepatology 2010)
Synovial T cell proliferation to the Yersinia enterocolitica 19 kDa antigen differentiates yersinia triggered reactive arthritis (ReA) from ReA triggered by other enterobacteria
Authors: H Appel
Journal: Annals of the Rheumatic Diseases (2002)

Blockade of tumour necrosis factor alpha (TNFα) using infliximab, a chimeric monoclonal antibody against TNFα, is an effective treatment in rheumatoid arthritis and Crohn's disease. 1 2 Sifikakis reported success using infliximab in sight threatening Behçet's disease. 3 A preliminary study has also reported clinical improvements in the primary systemic vasculitis, Wegener's granulomatosis, with the soluble TNFα receptor etanercept. 4 The benefit of lenercept, a soluble p55 TNFα receptor fusion protein, on digital vasculitis in rheumatoid arthritis has also been reported. 5 We report the compassionate treatment of six patients with refractory vasculitis using infliximab.Diagnoses were Wegener's granulomatosis in three and microscopic polyangiitis in three.Three patients were positive for proteinase-3 antineutrophil cytoplasmic antibodies (PR3-ANCA) and one for myeloperoxidase (MPO)-ANCA.Four were female, with a mean age of 58 years (range 23-77) and mean disease duration of 3.5 years.All had had at least three clinical relapses and had received prolonged treatment with corticosteroids and at least four immunosuppressive drugs.At the time of infliximab treatment the eyes were affected in four patients and the lung in three; in addition, five had profound constitutional symptoms.The mean prednisolone dose was 17 mg.Three intravenous doses of infliximab 200 mg were given at monthly intervals for three months.One patient complained of fatigue, myalgia, and blurred vision 24 hours after the first infusion, which did not recur on rechallenge.Infliximab was otherwise well tolerated.Five patients had remission of their disease, four within two weeks of treatment.This allowed steroid withdrawal in three and reduction by more than 50% in two.Disease activity assessed by the Birmingham Vasculitis Activity Scores (BVAS) improved from a mean of 6.3 to 0.8 at three months (fig 1). 6 One patient receiving continued infliximab for six months relapsed when the treatment interval was extended to two months.Mean falls in erythrocyte sedimentation rate and C reactive protein were 17 mm/1st h and 13 mg/l, respectively.The ANCA status was unchanged.Anti-TNFα treatment heralds a new wave of specifically targeted biological interventions of potential value in the treatment of vasculitis.It offers the hope of improved therapeutic efficacy over current agents and the possibility of reducing exposure to steroids and immunosuppressive drugs.Further studies are warranted to confirm these observations and explore the role of infliximab as a component of initial protocols.. . . . . .
Quality of Randomized Controlled Trials Reporting in the Treatment of Sarcomas
Authors: Maud Toulmonde, Carine Bellera, Simone Mathoulin-Pelissier, Marc Debled, Binh Bui, Antoine Italiano
Journal: Journal of Clinical Oncology (2011)

Purpose Randomized controlled trials (RCTs) represent the best evidence in oncology practice. The aim of this study was to assess the reporting quality of sarcoma RCTs and to identify significant predictors of quality. Patients and Methods Two investigators searched MEDLINE for pediatric and adult bone and soft tissue sarcoma RCTs published between January 1988 and December 2008. The quality of each report was assessed by using a 15-point overall reporting quality score based on 15 items from the revised Consolidated Standards of Reporting Trials (CONSORT) statement (overall quality score [OQS] range, 0 to 15 points). Concealment of allocation, appropriate blinding, and analysis according to intention-to-treat principle were assessed separately because of their crucial methodologic importance by using a 3-point key methodologic index score (MIS; range, 0 to 3). Results We retrieved 72 relevant RCTs that included 16,029 patients. The median OQS was 9.5. Allocation concealment, blinding, and analysis by intent to treat were reported only in 21 (29%), nine (12.5%), and 23 (32%) of the 72 RCTs, respectively. The median MIS was 1 with a minimum of 0 and a maximum of 2. On multivariate analysis, publication after 1996 and high impact factor remained independent and significant predictors of improved OQS. The sole variable associated with improved MIS was the publication of chemotherapy-only trials. Conclusion Although the overall quality of sarcoma RCTs reporting has improved over time, reporting of key methodologic issues remains poor. This may lead to biased interpretation of sarcoma trial results.
Single-agent gemcitabine versus cisplatin-etoposide: Early results of a randomised phase II study in locally advanced or metastatic non-small-cell lung cancer
Authors: C. Manegold, B. Bergman, A. Chemaissani, W. Dornoff, P. Drings, P. Kellokumpu-Lehtinen, K. Liippo, K. Mattson, J.v. Pawel, S. Ricci, C. Sederholm, R.A. Stahel, G. Wagenius, N.v. Walree, W. ten Bokkel-Huinink
Journal: Annals of Oncology (1997)
Efficacy and safety of comfrey root extract ointment in the treatment of acute upper or lower back pain: results of a double-blind, randomised, placebo controlled, multicentre trial
Authors: B M Giannetti, C Staiger, M Bulitta, H-G Predel
Journal: British Journal of Sports Medicine (2009)

Objective The objective was to show the superiority of comfrey root extract ointment to placebo ointment in patients with acute upper or lower back pain. Design The study was conducted as a double-blind, multicentre, randomised clinical trial with parallel group design over a period of 5 days (SD 1). The patients (n = 120, mean age 36.9 years) were treated with verum or placebo ointment three times a day, 4 g ointment per application. The trial included four visits. Main Outcome Measures The primary efficacy variable was the area under the curve (AUC) of the visual analogue scale (VAS) on active standardised movement values at visits 1 to 4. The secondary efficacy variables were back pain at rest using assessment by the patient on VAS, pressure algometry (pain–time curve; AUC over 5 days), global assessment of efficacy by the patient and the investigator, consumption of analgesic medication and functional impairment measured using the Oswestry disability index. Results There was a significant treatment difference between comfrey extract and placebo regarding the primary variable. In the course of the trial the pain intensity on active standardised movement decreased on average (median) approximately 95.2% in the verum group and 37.8% in the placebo group. Conclusions The results of this clinical trial were clear-cut and consistent across all primary and secondary efficacy variables. Comfrey root extract showed a remarkably potent and clinically relevant effect in reducing acute back pain. For the first time a fast-acting effect of the ointment (1 h) was also witnessed.
Cardiovascular Side Effects of Antiobesity Drugs
Authors: Allyn L. Mark
Journal: Circulation (2009)

surge in obesity with its attendant increase in diabetes mellitus, dyslipidemia, hypertension, and cardiovascular disease is provoking alarm.Fortunately, the surge in obesity has been paralleled by a revolution in understanding the biological regulation of appetite, metabolism, and adiposity. 1,2Mushrooming discoveries are identifying new pathways regulating appetite and metabolism.These pathways are potential new therapeutic targets, but we still lack safe effective pharmacotherapy for obesity.Consequently, the effort to develop safe, effective pharmacotherapy goes on, fueled by the discovery of new biological mechanisms and new therapeutic targets regulating appetite and metabolism.
BRITISH HEALTH RESORTS FOR FOREIGN INVALIDS
Authors: G. Monod
Journal: BMJ (1911)

eg., of a connexion between genius and epilepsy, never very widely favoured by physicians, may now be regarded as definitely disproved.Nor are the weak and diseased tendencies, of which genius has been actually convicted, of a kind which any sensible person would regard as pro- hibitive of marriage.In a quite different category, however, from these is the case in which an individual who possesses genius may have constitutional proclivities which make it likely that his children, if he had any, would be insane or tuberculous or epileptic.Undtr such circumstances the possibility that genius might be transmitted would be no
Cervical injury in rugby football--a New Zealand survey.
Authors: H. C. Burry, H. Gowland
Journal: British Journal of Sports Medicine (1981)

In a study of cervical injury in New Zealand rugby football in the years 1973 to 1978 inclusive, 54 cases of injury were identified of which five were fatal. There is no evidence that the incidence of these injuries is increasing. Incomplete figures for the season of 1979/80 include two deaths and 14 cases of permanent cord compression or temporary quadriplegia. The scrum is confirmed as a danger area but the danger occurring during the formation of the scrum is seen to be greater than was previously thought. Young players appear to be particularly vulnerable in scrums. The ruck and maul are danger areas. One-third of the accidents occurred during training or social games. It is concluded that the incidence of injury could be reduced by appropriate player selection, better coaching and amendment of the laws. Since only one player was aware of his danger at the time of his accident, it would seem that coaching with an emphasis on awareness and precautionary measures would be effective in prevention of cervical injury.
Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations
Authors: Meghan Clements, Michael Gershenovich, Christopher Chaber, Juanita Campos-Rivera, Pan Du, Mindy Zhang, Steve Ledbetter, Anna Zuk
Journal: Journal of the American Society of Nephrology (2015)

Macrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear. In this study, we used a renal bilateral ischemia-reperfusion injury mouse model to identify unique monocyte/macrophage populations by differential expression of Ly6C in CD11b(+) cells and to define the function of these cells in the pathophysiology of disease on the basis of microarray gene signatures and reduction strategies. Macrophage populations were isolated from kidney homogenates by fluorescence-activated cell sorting for whole genome microarray analysis. The CD11b(+)/Ly6C(high) population associated with the onset of renal injury and increase in proinflammatory cytokines, whereas the CD11b(+)/Ly6C(intermediate) population peaked during kidney repair. The CD11b(+)/Ly6C(low) population emerged with developing renal fibrosis. Principal component and hierarchical cluster analyses identified gene signatures unique to each population. The CD11b(+)/Ly6C(intermediate) population had a distinct phenotype of wound healing, confirmed by results of studies inhibiting the macrophage colony-stimulating factor 1 receptor,whereas the CD11b(+)/Ly6C(low) population had a profibrotic phenotype. All populations, including the CD11b(+)/Ly6C(high) population, carried differential inflammatory signatures. The expression of M2-specific markers was detected in both the CD11b(+)/Ly6C(intermediate) and CD11b(+)/Ly6C(low) populations, suggesting these in vivo populations do not fit into the traditional classifications defined by in vitro systems. Results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b(+)/Ly6C(+) monocyte/macrophage populations in the pathophysiology of disease after AKI.
Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading
Authors: Nicolaas de Jonge, Dick F. van Wichen, Marguerite E.I. Schipper, Jaap R. Lahpor, Frits H.J. Gmelig-Meyling, Etienne O. Robles de Medina, Roel A. de Weger
Journal: Journal of the American College of Cardiology (2002)
Biomonitoring with Wireless Communications
Authors: Thomas F. Budinger
Journal: Annual Review of Biomedical Engineering (2003)

▪ Abstract Wireless biomonitoring, first used in human beings for fetal heart-rate monitoring more than 30 years ago, has now become a technology for remote sensing of patients' activity, blood pulse pressure, oxygen saturation, internal pressures, orthopedic device loading, and gastrointestinal endoscopy. Technical advances in miniaturization and wireless communications have enabled development of monitoring devices that can be made available for general use by individuals/patients and caregivers. New methods for short-range wireless communications not encumbered by radio spectrum restrictions (e.g., ultra-wideband) will enable applications of wireless monitoring without interference in ambulatory subjects, in home care, and in hospitals.
Relation between flow-pressure-diameter studies in experimental stenosis of rabbit and human small bowel.
Authors: P Morel, J Alexander-Williams, A Rohner
Journal: Gut (1990)

Patients with inflammatory and ischaemic bowel diseases seem to tolerate narrowing of the gut lumen to a critical degree of stenosis without obstructive symptoms. To determine the physical factors involved in bowel occlusion, we created an experimental model using New Zealand rabbits in acute experiments under general anaesthesia. At operation a loop of small bowel was isolated and canulated, proximally for perfusion and pressure recording and distally to monitor flow. Having established the physiological pressure and flow conditions in a normal loop of gut, a stenosis was created using circular adjustable rings of determined widths. Pressure and flow were measured constantly and the variables studied were luminal diameter, stenosis length, and perfusate viscosity. This experimental model was reproduced using resected segments of human small bowel. We found a critical point- at 60% of the original diameter-down to which the small bowel is able to maintain normal flow. At a diameter smaller than this, the physiological parameters are rapidly altered up to the point of complete obstruction. In the rabbit model bowel rupture occurs at 30% of the initial size. Increased viscosity of the fluid and length of the stenosis alter this critical point inducing a larger critical diameter. We did not observe any cumulative effect of multiple identical stenoses.