tbuckley/cabot-search huggingface dataset:
Acute Isolated Transmural Neutropenic Gastritis
Authors: Andrew J. King, Toby Eyre, Deepa Rangarajan, Rebecca Sampson, Henri Grech
Journal: Journal of Clinical Oncology (2011)

Case ReportA 56-year-old woman with acute myeloid leukemia was admitted to our unit in January 2010 for her second cycle of chemotherapy with daunorubicin and cytarabine.Before her diagnosis, she had no medical problems.At diagnosis, she was found to have an incidental factor VII deficiency.Her bone marrow karyotype was normal, and she was found to have an activating mutation of FMS-like tyrosine kinase 3 (FLT3).She was enrolled onto the acute myeloid leukemia (AML) 17 trial and randomly assigned to receive daunorubicin and cytarabine with the FMS-like tyrosine kinase-3 inhibitor, lestaurtinib.The first cycle was complicated by neutropenic sepsis requiring broad spectrum antibiotics and antifungal therapy; no organisms were isolated.She also experienced melena and mild epigastric pain, which were presumed secondary to a combination of mucositis, thrombocytopenia, and factor VII deficiency.This settled with platelet transfusions and prothrombin complex concentrate; therefore, an esophagogastroduodenoscopy was not performed.Remission was achieved after the first cycle of induction chemotherapy.Cycle two proceeded without complication until day 27 (from the start of the cycle), when she developed vomiting followed by severe epigastric pain, hypotension, and tachycardia.Her neutrophil count was 0.09 ϫ 10 9 /L.An urgent computed tomography (CT) scan demonstrated an isolated, markedly abnormal, thick-walled stomach with normal small and large intestine (Fig 1A; arrow, stomach).She was transferred to the intensive care unit for inotropic support with noradrenaline and vasopressin.Meropenem, gentamicin, and granulocyte colony-stimulating factor (G-CSF) were commenced.Recovery of her neutrophil count was mirrored by a remarkable clinical improvement with rapid weaning of inotropes and return to ward-based care within 4 days.A CT scan 2 weeks later after neutrophil count
Pralidoxime in Acute Organophosphorus Insecticide Poisoning—A Randomised Controlled Trial
Authors: Michael Eddleston, Peter Eyer, Franz Worek, Edmund Juszczak, Nicola Alder, Fahim Mohamed, Lalith Senarathna, Ariyasena Hittarage, Shifa Azher, K. Jeganathan, Shaluka Jayamanne, Ludwig von Meyer, Andrew H. Dawson, Mohamed Hussain Rezvi Sheriff, Nick A. Buckley
Journal: PLoS Medicine (2009)

Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.
Controlled trial of cycled antibiotic prophylaxis to prevent initial Pseudomonas aeruginosa infection in children with cystic fibrosis
Authors: G. A. Tramper-Stranders, T. F. W. Wolfs, S. van Haren Noman, W. M. C. van Aalderen, A. F. Nagelkerke, M. Nuijsink, J. L. L. Kimpen, C. K. van der Ent
Journal: Thorax (2010)

<h3>Background</h3> Initial pulmonary <i>Pseudomonas aeruginosa</i> infection in patients with cystic fibrosis (CF) is currently treated with intensive antibiotic therapy. At this stage, inflammation and tissue injury might have already occurred. Moreover, bacterial eradication is not always achieved. Prophylactic treatment against <i>P aeruginosa</i> seemed to have a preventive effect in retrospective studies. A study was undertaken to establish prospectively the effect of cycled prophylactic treatment on prevention of initial <i>P aeruginosa</i> infection in children with CF. <h3>Methods</h3> This 3-year triple-blind randomised controlled trial included 65 children with CF without <i>P aeruginosa</i> infection. Intervention existed of 3-monthly 3-week treatments with oral ciprofloxacin and inhaled colistin or both placebo controls. The primary outcome was <i>P aeruginosa</i> infection. Secondary outcomes were serum anti-<i>Pseudomonas</i> antibodies, pulmonary function, exacerbations, chest x-ray scores, inflammation parameters, respiratory pathogens and antimicrobial resistance. <h3>Results</h3> There was no difference in acquisition of <i>P aeruginosa</i> infection between the control and treatment groups (annual incidence 14% vs 11%; HR 0.738, 95% CI 0.299 to 1.822). Anti-<i>Pseudomonas</i> antibodies emerged earlier in the control group, but this difference had disappeared after 3 years. Chronic infection was observed in 19% of controls and 12% of treated patients. Decline in pulmonary function and other clinical outcomes did not differ between the two groups. In the treatment group, significantly fewer Gram-positive bacteria and Enterobacteriaceae were observed but there were more non-<i>P aeruginosa</i> non-fermentative Gram-negative bacteria. <h3>Conclusions</h3> Three-monthly cycled anti-<i>P aeruginosa</i> prophylaxis does not reduce the risk of initial and chronic infection in <i>P aeruginosa</i>-negative children with CF of all ages. Shifts in bacterial colonisation demand caution. <h3>Trial Registration Number</h3> ISRCTN 11604593.
Air Pollution and Nonmalignant Respiratory Mortality in 16 Cohorts within the ESCAPE Project
Authors: Konstantina Dimakopoulou, Evangelia Samoli, Rob Beelen, Massimo Stafoggia, Zorana Jovanovic Andersen, Barbara Hoffmann, Paul Fischer, Mark Nieuwenhuijsen, Paolo Vineis, Wei Xun, Gerard Hoek, Ole Raaschou-Nielsen, Anna Oudin, Bertil Forsberg, Lars Modig, Pekka Jousilahti, Timo Lanki, Anu Turunen, Bente Oftedal, Per Nafstad, Per E. Schwarze, Johanna Penell, Laura Fratiglioni, Niklas Andersson, Nancy Pedersen, Michal Korek, Ulf De Faire, Kirsten Thorup Eriksen, Anne Tjønneland, Thomas Becker, Meng Wang, Bas Bueno-de-Mesquita, Ming-Yi Tsai, Marloes Eeftens, Petra H. Peeters, Kees Meliefste, Alessandro Marcon, Ursula Krämer, Thomas A.J. Kuhlbusch, Mohammad Vossoughi, Timothy Key, Kees de Hoogh, Regina Hampel, Annette Peters, Joachim Heinrich, Gudrun Weinmayr, Hans Concin, Gabriele Nagel, Alex Ineichen, Bénédicte Jacquemin, Morgane Stempfelet, Alice Vilier, Fulvio Ricceri, Carlotta Sacerdote, Xanthi Pedeli, Michalis Katsoulis, Antonia Trichopoulou, Bert Brunekreef, Klea Katsouyanni
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Prospective cohort studies have shown that chronic exposure to particulate matter and traffic-related air pollution is associated with reduced survival. However, the effects on nonmalignant respiratory mortality are less studied, and the data reported are less consistent.We have investigated the relationship of long-term exposure to air pollution and nonmalignant respiratory mortality in 16 cohorts with individual level data within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE).Data from 16 ongoing cohort studies from Europe were used. The total number of subjects was 307,553. There were 1,559 respiratory deaths during follow-up.Air pollution exposure was estimated by land use regression models at the baseline residential addresses of study participants and traffic-proximity variables were derived from geographical databases following a standardized procedure within the ESCAPE study. Cohort-specific hazard ratios obtained by Cox proportional hazard models from standardized individual cohort analyses were combined using metaanalyses. We found no significant associations between air pollution exposure and nonmalignant respiratory mortality. Most hazard ratios were slightly below unity, with the exception of the traffic-proximity indicators.In this study of 16 cohorts, there was no association between air pollution exposure and nonmalignant respiratory mortality.
Immunologic responses to xenogeneic tyrosinase DNA vaccine administered by electroporation in patients with malignant melanoma
Authors: Jianda Yuan, Geoffrey Y Ku, Matthew Adamow, Zhenyu Mu, Sapna Tandon, Drew Hannaman, Paul Chapman, Gary Schwartz, Richard Carvajal, Katherine S Panageas, Alan N Houghton, Jedd D Wolchok
Journal: Journal for ImmunoTherapy of Cancer (2013)

Prior studies show that intramuscular injection and particle-mediated epidermal delivery of xenogeneic melanosomal antigens (tyrosinase or Tyr, gp100) induce CD8(+) T cell responses to the syngeneic protein. To further define the optimal vaccination strategy, we conducted a phase I study of in vivo electroporation (EP) of a murine Tyr DNA vaccine (pINGmuTyr) in malignant melanoma patients.Human leukocyte antigen (HLA)-A1, A2, A24 or B35 stage IIb-IV melanoma patients received up to five doses of the mouse tyrosinase DNA vaccine by EP every three weeks at dose levels of 0.2 mg, 0.5 mg, or 1.5 mg per injection. Peripheral blood mononuclear cells (PBMC) were collected, cultured with a peptide pool containing eight HLA class I-restricted Tyr-specific T-cell epitopes, and analyzed by HLA-A*0101-restricted tetramers and intracellular cytokine staining (ICS).Twenty-four patients received ≥1 dose of the pINGmuTyr vaccine; PBMCs from 21 patients who completed all five doses were available for Tyr immune assays. The only common toxicity was grade 1 injection site reaction. Six of 15 patients (40%) in the 1.5 mg dose cohort developed Tyr-reactive CD8(+) T cell responses following stimulation, defined as a ≥3 standard deviation increase in baseline reactivity by tetramer or ICS assays. No Tyr-reactive CD8(+) T cell response was detected in the 0.2 mg and 0.5 mg dose cohort patients. Epitope spreading of CD8(+) T cell response to NY-ESO-1 was observed in one patient with vitiligo. One patient subsequently received ipilimumab and developed an enhanced Tyr-reactive response with polyfunctional cytokine profile. After a median follow-up of 40.9 months, median survival has not been reached.A regimen of five immunizations with pINGmuTyr administered by EP was found to be safe and resulted in Tyr-reactive immune responses in six of 15 patients at 1.5 mg dose cohort.ClinicalTrials.gov NCT00471133.
<i>PAX3-FKHR</i> and <i>PAX7-FKHR</i> Gene Fusions Are Prognostic Indicators in Alveolar Rhabdomyosarcoma: A Report From the Children’s Oncology Group
Authors: Poul H.B. Sorensen, James C. Lynch, Stephen J. Qualman, Roberto Tirabosco, Jerian F. Lim, Harold M. Maurer, Julia A. Bridge, William M. Crist, Timothy J. Triche, Frederic G. Barr
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue malignancy of children and adolescents. Most ARMS patients express PAX3-FKHR or PAX7-FKHR gene fusions resulting from t(2;13) or t(1;13) translocations, respectively. We wished to confirm the diagnostic specificity of gene fusion detection in a large cohort of RMS patients and to evaluate whether these alterations influence clinical outcome in ARMS. PATIENTS AND METHODS: We determined PAX3-FKHR or PAX7-FKHR fusion status in 171 childhood rhabdomyosarcoma (RMS) patients entered onto the Intergroup Rhabdomyosarcoma Study IV, including 78 ARMS patients, using established reverse transcriptase polymerase chain reaction assays. All patients received central pathologic review and were treated using uniform protocols, allowing for meaningful outcome analysis. We examined the relationship between gene fusion status and clinical outcome in the ARMS cohort. RESULTS: PAX3-FKHR and PAX7-FKHR fusion transcripts were detected in 55% and 22% of ARMS patients, respectively; 23% were fusion-negative. All other RMS patients lacked transcripts, confirming the specificity of these alterations for ARMS. Fusion status was not associated with outcome differences in patients with locoregional ARMS. However, in patients presenting with metastatic disease, there was a striking difference in outcome between PAX7-FKHR and PAX3-FKHR patient groups (estimated 4-year overall survival rate of 75% for PAX7-FKHR v 8% for PAX3-FKHR; P = .0015). Multivariate analysis demonstrated a significantly increased risk of failure (P = .025) and death (P = .019) in patients with metastatic disease if their tumors expressed PAX3-FKHR. Among metastatic ARMS, bone marrow involvement was significantly higher in PAX3-FKHR–positive patients. CONCLUSION: Not only are PAX-FKHR fusion transcripts specific for ARMS, but expression of PAX3-FKHR and PAX7-FKHR identifies a very high-risk subgroup and a favorable outcome subgroup, respectively, among patients presenting with metastatic ARMS.
Expression and function of Fas (CD95) on human renal tubular epithelial cells.
Authors: J G Boonstra, F J van der Woude, P C Wever, J C Laterveer, M R Daha, C van Kooten
Journal: Journal of the American Society of Nephrology (1997)

Renal transplant rejection is characterized by an influx of mononuclear cells in the tubulointerstitial area. Recent studies indicate that tubular damage during graft rejection is dependent, at least in part, on apoptosis. It is thought that apoptosis may be induced by the mononuclear cell infiltrate via the perforin/granzyme or the Fas/Fas ligand pathway. Fas is a 43-kD member of the tumor necrosis factor receptor family, and ligation results in apoptosis of the Fas-bearing cell. The present study analyzes whether Fas is expressed on human tubular epithelial cells in situ and in vitro. It was found that 50 to 70% of the tubules in renal tissue exhibited a positive staining for Fas. To further study the occurrence of Fas on tubular cells, eight different primary proximal tubular epithelial cell (PTEC) lines were analyzed for Fas expression. More than 90% of the PTEC were positive for Fas, and treatment with IFN-gamma resulted in an even higher expression. To determine whether Fas ligation resulted in apoptosis of PTEC in culture, PTEC were incubated with two different anti-Fas antibodies, which were able to induce apoptosis in Jurkat cells. No apoptotic PTEC were observed after Fas ligation, as determined by morphological staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling analysis. Simultaneous CD40 and Fas ligation, or treatment with IFN-gamma before Fas ligation, also did not result in the induction of apoptosis. Fas ligation did not result in proliferation or activation of PTEC, as measured by interleukin-8 production. Apoptotic PTEC could only be detected when the cells were incubated with both anti-Fas antibodies and cycloheximide, resulting in up to 92% apoptotic cells. This study demonstrates that although renal tubular epithelial cells express Fas, they appear to be resistant to Fas-mediated apoptosis, suggesting that Fas-mediated apoptosis does not play a role in the induction of apoptosis during renal transplant rejection.
Cardiac Membrane Fatty Acid Composition Modulates Myocardial Oxygen Consumption and Postischemic Recovery of Contractile Function
Authors: Salvatore Pepe, Peter L. McLennan
Journal: Circulation (2002)

Background — Regular fish consumption is associated with low cardiovascular disease morbidity and mortality. Fish oils modify cardiac membrane phospholipid fatty acid composition with potent antiarrhythmic effects. We tested the effects of dietary fish oil on ventricular hemodynamics and myocardial oxygen consumption (MVO 2 ). Methods and Results — Male Wistar rats were fed for 16 weeks on a reference diet rich in n -6 polyunsaturated fatty acids (PUFA), a diet rich in saturated animal fat (SAT), or a diet rich in n -3 PUFA from fish oil. Isolated working hearts were perfused with porcine erythrocytes (40% hematocrit) at 75 mm Hg afterload with variable preload (5 to 20 mm Hg) or with low coronary flow ischemia with maintained afterload, preload, and heart rate, then reperfused. MVO 2 was low and coronary perfusion reserve high in n -3 PUFA hearts, and cardiac output increased with workload. The n -3 PUFA reduced ischemic markers—acidosis, K + , lactate, and creatine kinase—and increased contractile recovery during reperfusion. SAT hearts had high MVO 2 , low coronary perfusion reserve, and poor contractile function and recovery. Dietary differences in MVO 2 were abolished by KCl arrest (basal metabolism) or ruthenium red (3.4 μmol/L) but not by ryanodine (1 nmol/L). Fish oil or ryanodine, but not ruthenium red, prevented ventricular fibrillation in reperfusion. Conclusions — Dietary fish oil directly influenced heart function and improved cardiac responses to ischemia and reperfusion. The n -3 PUFA reduced oxygen consumption at any given work output and increased postischemic recovery. Thus, direct effects on myocardial function may contribute to the altered cardiovascular disease profile associated with fish consumption.
Idiopathic Fanconi syndrome in a family. Part I. Clinical aspects.
Authors: A Tolaymat, A Sakarcan, R Neiberger
Journal: Journal of the American Society of Nephrology (1992)

Fanconi syndrome is a rare cause of rickets in children. Only six families with Fanconi syndrome following an autosomal dominant pattern of inheritance have been reported. In this report, the results of clinical studies performed in three generations of a family of 39 members with autosomal dominant Fanconi syndrome are presented. Twenty-one members of this family provided blood and urine for biochemical evaluation. Many family members have one or more tubular reabsorptive abnormalities; however, the complete Fanconi syndrome was not present in most members. Three children with the complete syndrome all occur in the last generation. When the characteristic features of this family were compared with those of previously reported families with autosomal dominant Fanconi syndrome, several differences became apparent. Two serious manifestations, diabetes mellitus and renal failure, which occur in previous reports did not occur in this family. This report provides information on apparently the largest number of affected individuals in a single family with Fanconi syndrome. In addition, variable expressivity of tubular reabsorptive defects in a family with Fanconi syndrome has never been reported.
Bronchial compression as a result of lung herniation after pneumonectomy.
Authors: C J Westermann, J P Janssen
Journal: Thorax (1992)

absorptiometry (DEXA) in corticosteroid associated osteoporosis.We reported to the summer 1991 meeting ofthe British Thoracic Society' our experience of 19 patients (13 female) with corticosteroid dependent asthma.Twelve of these patients had sustained at least one vertebral compression fracture.The mean corticosteroid dose and treatment duration for this fracture group was 10-1 mg prednisolone/day for 13-1 years and 13-9 mg prednisolone/day for 9-6 years in those patients without fracture (NS).The mean L2-L4 density was significantly lower in those patients with fractures (0-797 g/cm' versus 1-143 g/cm', p < 0-0001).The mean neck of femur density was also significantly lower in those patients with fractures (0-718 g/cm2 versus 0-901 g/cm2, p < 0 005).The study by Dr Luengo and colleagues used dual photon densitometry, which is known to be a less precise measure than DEXA,' and this may explain why in their study, though spinal density was higher in asthmatic patients without fractures, the difference was not statistically significant.It would appear therefore that a single measure of L2-L4 density by DEXA is a useful screening test for corticosteroid associated osteoporosis.Finally, in their discussion the authors ignore the effect of the menopause on the changes described.There is significant evidence that premenopausal women, who (though it is not stated) probably make up most of "group 1," are protected from corticosteroid associated osteoporosis, presumably by the effects of oestrogen.
Malaria infection changes the ability of splenic dendritic cell populations to stimulate antigen-specific T cells
Authors: Anne-Marit Sponaas, Emma Tamsin Cadman, Cecile Voisine, Vicky Harrison, Andre Boonstra, Anne O'Garra, Jean Langhorne
Journal: The Journal of Experimental Medicine (2006)

The capacity of splenic CD11c+ dendritic cell (DC) populations to present antigen (Ag) to T cells differs during malarial infection with Plasmodium chabaudi in mice. Both CD11c+CD8+ and CD8− DCs presented malarial peptides on their surface during infection. However, although both DC subsets expressing malaria peptides could induce interferon-γ production by CD4 T cells, only CD8− DCs isolated at the acute phase of infection stimulated Ag-specific T cell proliferation and interleukin (IL)-4 and -10 production from MSP1-specific T cell receptor for Ag transgenic T cells coincidental with our reported Th1 to Th2 switch at this stage in response to the pathogen. The timing of these distinct DC responses coincided with increased levels of apoptosis in the CD8+ population and an increase in the numbers of CD8− DCs in the spleen. Our data suggest that the switch in CD4 T cell responses observed in P. chabaudi–infected mice may be the result of the presentation by different DC populations modified by the malaria infection.