tbuckley/cabot-search huggingface dataset:
Genotyping mycobacterium avium has a clinical potential to predict therapeutic responses of the lung infection
Authors: Toshiaki Kikuchi, Yoshihiro Kobashi, Akira Watanabe, Masakazu Ichinose
Journal: European Respiratory Journal (2013)

For Mycobacterium avium lung infection, the lack of reliable predictors other than the relatively uncommon macrolide resistance represents a major limitation to clinical management. To investigate a potent predictor for the therapeutic response, we evaluated variable numbers of tandem repeats (VNTR) at 16 minisatellite loci of M. avium clinical isolates from 59 subjects with the lung infection. The disease of 30 subjects was defined as responsive for the microbiologic and radiographic improvement after clarithromycin-containing treatments, while that of the remaining 29 subjects was defined as refractory even after the similar treatment. When calculating the genotypic distance aggregated from 16-demensional VNTR data, we observed the genetic diversity of 59 M. avium isolates divided into 3 clusters in neighbor-joining phylogenetic tree, which revealed the nearly significant association with therapeutic responses ( P = 0.06). In principal component analysis using the raw VNTR data without the distance calculation, we detected a significant correlation between the therapeutic responses and the scattering pattern of 59 M. avium isolates ( P < 0.05). In further analysis by logistic regression, we examined the effect of each minisatellite locus on a predictive model of the therapeutic response. This led us to construct the highest likelihood multivariate model, adjusted for age, with a sensitivity and specificity both greater than 70%, using VNTR data from only four minisatellite loci ( P < 0.01). Genotypic characterization of M. avium isolates may be a useful strategy for predicting the clinical outcome of medication.
Exact moment of a gastrocnemius muscle strain captured on video
Authors: J W Orchard, E Alcott, T James, P Farhart, M Portus, S R Waugh
Journal: British Journal of Sports Medicine (2002)

A left gastrocnemius strain was sustained by an elite cricket batsman while he was taking off to run. The exact moment of injury, captured by a camera in the middle stump, appears to correspond to the sudden appearance of a deficit in the gastrocnemius muscle, seen through the player's trousers. The strain occurred when the entire body weight was on the left foot with the centre of mass well in front of the leg. The injury probably occurred close to the time when the gastrocnemius complex was moving from an eccentric to an isometric phase.
Prostate Cancer Immunotherapy
Authors: Kenneth F. May, James L. Gulley, Charles G. Drake, Glenn Dranoff, Philip W. Kantoff
Journal: Clinical Cancer Research (2011)

Abstract The interaction between the immune system and prostate cancer has been an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of 2 first-in-class proof-of-concept immunotherapies (sipuleucel-T and ipilimumab) has stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies that have garnered the most interest are the therapeutic vaccination strategies, exemplified by sipuleucel-T and PROSTVAC-VF, and immune checkpoint blockade of CTLA-4 and PD-1. Improved understanding of the immune responses generated by these strategies and development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide building blocks for future immunotherapies. Clin Cancer Res; 17(16); 5233–8. ©2011 AACR.
Long-term acceptance of major histocompatibility complex mismatched cardiac allografts induced by CTLA4Ig plus donor-specific transfusion.
Authors: H Lin, S F Bolling, P S Linsley, R Q Wei, D Gordon, C B Thompson, L A Turka
Journal: The Journal of Experimental Medicine (1993)

Allograft rejection is a T cell-dependent process. Productive T cell activation by antigen requires antigen engagement of the T cell receptor as well as costimulatory signals delivered through other T cell surface molecules such as CD28. Engagement of CD28 by its natural ligand B7 can be blocked using a soluble recombinant fusion protein, CTLA4Ig. Administration of CTLA4Ig blocks antigen-specific immune responses in vitro and in vivo, and we have shown that treatment of rats with a 7-d course of CTLA4Ig at the time of transplantation leads to prolonged survival of cardiac allografts (median 30 d), although most grafts are eventually rejected. Here, we have explored additional strategies employing CTLA4Ig in order to achieve long-term allograft survival. Our data indicate that donor-specific transfusion (DST) plus CTLA4Ig can provide effective antigen-specific immunosuppression. When DST is administered at the time of transplantation followed by a single dose of CTLA4Ig 2 d later, all animals had long-term graft survival (> 60 d). These animals had delayed responses to donor-type skin transplants, compared with normal rejection responses to third-party skin transplants. Furthermore, donor-matched second cardiac allografts were well tolerated with minimal histologic evidence of rejection. These data indicate that peritransplant use of DST followed by subsequent treatment with CTLA4Ig can induce prolonged, often indefinite, cardiac allograft acceptance. These results may be clinically applicable for cadaveric organ and tissue transplantation in humans.
Urinary copper excretion in rheumatoid arthritis.
Authors: W McMurray, V M Martin, P Scudder, J Stocks, A G White, T L Dormandy
Journal: Annals of the Rheumatic Diseases (1975)

The pattern of urinary copper excretion in relation to urine osmolality (as shown by series of aliquots of urine) was studied in rheumatoid patients and in control groups. Rheumatoid patients showed an abnormal copper excretion pattern compared with nonrheumatoid subjects. This was not a direct function of the raised serum copper in rheumatoid disease. Measurements based on 24-hour series of aliquots of urine (as distinct from total pooled 24-hour collections) have been shown to be a useful and sensitive method for studying copper excretion patterns.
Sorafenib in Combination With Intensive Chemotherapy in Elderly Patients With Acute Myeloid Leukemia: Results From a Randomized, Placebo-Controlled Trial
Authors: Hubert Serve, Utz Krug, Ruth Wagner, M. Cristina Sauerland, Achim Heinecke, Uta Brunnberg, Markus Schaich, Oliver Ottmann, Justus Duyster, Hannes Wandt, Thomas Fischer, Aristoteles Giagounidis, Andreas Neubauer, Albrecht Reichle, Walter Aulitzky, Richard Noppeney, Igor Blau, Volker Kunzmann, Reingard Stuhlmann, Alwin Krämer, Karl-Anton Kreuzer, Christian Brandts, Björn Steffen, Christian Thiede, Carsten Müller-Tidow, Gerhard Ehninger, Wolfgang E. Berdel
Journal: Journal of Clinical Oncology (2013)

The prognosis of elderly patients with acute myeloid leukemia (AML) is still dismal even with intensive chemotherapy. In this trial, we compared the antileukemic activity of standard induction and consolidation therapy with or without the addition of the kinase inhibitor sorafenib in elderly patients with AML.All patients received standard cytarabine and daunorubicin induction (7+3 regimen) and up to two cycles of intermediate-dose cytarabine consolidation. Two hundred one patients were equally randomly assigned to receive either sorafenib or placebo between the chemotherapy cycles and subsequently for up to 1 year after the beginning of therapy. The primary objective was to test for an improvement in event-free survival (EFS). Overall survival (OS), complete remission (CR) rate, tolerability, and several predefined subgroup analyses were among the secondary objectives.Age, sex, CR and early death (ED) probability, and prognostic factors were balanced between both study arms. Treatment in the sorafenib arm did not result in significant improvement in EFS or OS. This was also true for subgroup analyses, including the subgroup positive for FLT3 internal tandem duplications. Results of induction therapy were worse in the sorafenib arm, with higher treatment-related mortality and lower CR rates. More adverse effects occurred during induction therapy in the sorafenib arm, and patients in this arm received less consolidation chemotherapy as a result of higher induction toxicity.In conclusion, combination of standard induction and consolidation therapy with sorafenib in the schedule investigated in our trial is not beneficial for elderly patients with AML.
Tuberculosis as a Primary Cause of Respiratory Failure Requiring Mechanical Ventilation
Authors: Charles Penner, Daniel Roberts, Dennis Kunimoto, Jure Manfreda, Richard Long
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation (TBmv) is an uncommon occurrence. Over a 10 yr period in the province of Manitoba, Canada (population 1,091,942 in 1991), 13 patients with TBmv were identified. Non-drug-resistant M. tuberculosis was isolated from each case. The patients fell into two categories: miliary or disseminated tuberculosis (n = 7) and tuberculous pneumonia (n = 6); eight developed ARDS (adult respiratory distress syndrome) and another two probable ARDS. The hospital mortality for TBmv was compared with that for mechanically ventilated nontuberculous pneumonia and ARDS patients. Hospital mortality for patients with TBmv (69%, nine of 13) was significantly worse than hospital mortality for patients with nontuberculous pneumonia requiring mechanical ventilation (36%, 34 of 94; p < 0.025) and similar to the hospital mortality for patients with ARDS of any cause (56%, 15 of 27; p > 0.10). APACHE II scores for all groups of patients were similar. Compared with patients with tuberculous pneumonia, patients with miliary or disseminated tuberculosis were significantly more likely to develop TBmv (18.9 versus 0.8%, p < 0.0001). Despite the availability of effective antituberculous drugs, TBmv is often associated with ARDS and carries a similarly high mortality rate. Among patients with pulmonary tuberculosis, those with miliary or disseminated disease are especially prone to develop TBmv.
Prognostic Significance of Cyclooxygenase-2 in Oropharyngeal Squamous Cell Carcinoma
Authors: Bryan W. Chang, David H. Kim, Diane P. Kowalski, Joseph A. Burleson, Yung H. Son, Lynn D. Wilson, Bruce G. Haffty
Journal: Clinical Cancer Research (2004)

To determine the relative prognostic significance of cyclooxygenase (COX)-2 expression in patients with oropharyngeal squamous cell carcinoma (SCC).This retrospective cohort study included 82 patients with SCC referred to the Department of Therapeutic Radiology at Yale-New Haven Hospital (Connecticut) between 1980 and 1999 who were treated with primary external beam radiotherapy or gross total surgical resection and postoperative radiotherapy. A microarray of archival tumor tissue was constructed and stained with monoclonal antibodies directed against COX-2 and scored for intensity by a pathologist blinded to the clinical outcomes of the patients. COX-2 immunoreactivity and clinicopathological data were analyzed with respect to survival endpoints using bivariate and multivariate techniques.Frequency of COX-2 overexpression was 45%. In multivariate analysis, COX-2 positivity predicted poor 3-year survival (P = 0.02; odds ratio = 0.41; 95% confidence interval, 0.20-0.84). Increasing age was significantly associated with increased 3-year survival (P = 0.03; odds ratio = 1.04; 95% confidence interval, 1.004-1.09). Positive COX-2 status trended toward predicting decreased 3-year disease-free survival.COX-2 was the most important predictor of poor survival in this patient cohort. In patients with oropharyngeal SCC treated with external-beam radiation therapy, overexpression of COX-2 may affect clinical outcome, and COX-2 may therefore prove valuable both as a prognostic factor and as a therapeutic target.
Effect of glycine and glucose on sodium and water absorption in patients with cholera
Authors: D. R. Nalin, R. A. Cash, M. Rahman, Md. Yunus
Journal: Gut (1970)

Electrolyte solutions containing glucose, glycine, or a combination of the two were absorbed sufficiently well from the intestine to supply maintenance fluid and the electrolytes required by cholera patients. Data on net absorption and duration and volume of diarrhoea show that a solution containing both glucose and glycine provides more effective therapy than solutions containing either glucose or glycine alone.
Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A
Authors: Jenny Goudemand, Chantal Rothschild, Virginie Demiguel, Christine Vinciguerrat, Thierry Lambert, Hervé Chambost, Annie Borel-Derlon, Ségolène Claeyssens, Yves Laurian, Thierry Calvez
Journal: Blood (2005)
A prospective pilot trial of ablation of Barrett’s esophagus with low-grade dysplasia using stepwise circumferential and focal ablation (HALO system)
Authors: V. Sharma, H. Kim, A. Das, P. Dean, G. DePetris, D. Fleischer
Journal: Endoscopy (2008)

See also: Commentaire de "Traitement de l'œsophage de Barrett par radiofréquence" (4 articles), pp. 359Endoscopy 2008; 40(05): 453-454DOI: 10.1055/s-0032-1306830
Central Airway Obstruction
Authors: Armin Ernst, David Feller-Kopman, Heinrich D. Becker, Atul C. Mehta
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Central airway obstruction is a problem facing all medical and surgical subspecialists caring for patients with chest diseases. The incidence of this disorder appears to be rising because of the epidemic of lung cancer; however, benign causes of central airway obstruction are being seen more frequently as well. The morbidity is significant and if left untreated, death from suffocation is a frequent outcome. Management of these patients is difficult, but therapeutic and diagnostic tools are now available that are beneficial to most patients and almost all airway obstruction can be relieved expeditiously. This review examines current approaches in the workup and treatment of patients suffering from airway impairment. Although large, randomized, comparative studies are not available, data show significant improvement in patient outcomes and quality of life with treatment of central airway obstruction. Clearly, more studies assessing the relative utility of specific airway interventions and their impact on morbidity and mortality are needed. Currently, the most comprehensive approach can be offered at centers with expertise in the management of complex airway disorders and availability of all endoscopic and surgical options.
The Role of Hyperthermia in Regional Alkylating Agent Chemotherapy
Authors: Omar I. Abdel-Wahab, Elizabeth Grubbs, Benjamin L. Viglianti, Tsung-Yen Cheng, Tomio Ueno, SaeHee Ko, Zahid Rabbani, Simon Curtis, Scott K. Pruitt, Mark W. Dewhirst, Doug S. Tyler
Journal: Clinical Cancer Research (2004)

Abstract The role of hyperthermia during regional alkylating agent chemotherapy is controversial. The aim of this study was to determine the exact contribution of hyperthermia to tumor response during isolated limb infusion with l-phenylalanine mustard. Rats bearing rodent fibrosarcoma on the hindlimb underwent isolated limb infusion with saline, saline plus heat, l-phenylalanine mustard, l-phenylalanine mustard under conditions of normothermia, or l-phenylalanine mustard plus hyperthermia. Heat was administered locally using an in-line hot water circulation loop. Treatment with l-phenylalanine mustard at a concentration of 15 or 50 μg/mL was ineffective at producing tumor growth delay (P = 0.24 and 0.41, respectively). Furthermore, thermal enhancement of l-phenylalanine mustard activity was not seen at 15 μg/mL. However, administration of high-dose l-phenylalanine mustard, 50 μg/mL, with increasing amounts of heat yielded increasing tumor growth delay, increased regressions, and decreased proliferative index. Although l-phenylalanine mustard infusion under normothermia yielded a tumor growth delay of 7.1 days, combination l-phenylalanine mustard + hyperthermia treatment produced tumor growth delay of 27.0 days (P &amp;lt; 0.01; with two of five animals showing a complete response). Four hours after isolated limb infusion, 50.9% of cells in tumor treated with l-phenylalanine mustard + hyperthermia experienced apoptosis, whereas only 18.1, 16, and 4.4% of cells underwent apoptosis after treatment with l-phenylalanine mustard, saline + hyperthermia, or saline. The mean concentration of l-phenylalanine mustard within tumor relative to perfusate following isolated limb infusion was found to be similar among all groups at 0.023, 0.025, and 0.032 in animals undergoing isolated limb infusion with l-phenylalanine mustard, l-phenylalanine mustard + normothermia, and l-phenylalanine mustard + hyperthermia, respectively. These data indicate a synergistic cytotoxic effect of l-phenylalanine mustard + hyperthermia in isolated limb infusion, which is not attributable to enhanced tumor drug uptake.
Lung Disease Associated with the IVS8 5T Allele of the CFTR Gene
Authors: PEADAR G. NOONE, CHARLES A. PUE, ZHAOQING ZHOU, KENNETH J. FRIEDMAN, EMMA L. WAKELING, MUTTIAH GANESHANANTHAN, RICHARD H. SIMON, LAWRENCE M. SILVERMAN, MICHAEL R. KNOWLES
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. The 5T allele in intron 8 (IVS8) causes abnormal splicing in the CFTR gene, and is associated with lung disease when it occurs in cis with a missense mutation in the CFTR gene, R117H. However, the 5T variant alone has not been reported to cause lung disease. We describe two adult female patients with CF-like lung disease associated with the 5T allele. One patient's genotype is 5T-TG12-M470V/5T-TG12-M470V, and the other is Δ F508/5T-TG12-M470V; full sequencing of the CFTR gene revealed no other mutation on the same allele as the 5T variant. The levels of full-length CFTR mRNA in respiratory epithelia were very low in these patients (11 and 6%, respectively, of total CFTR mRNA expression). Both patients had defective CFTR-mediated chloride conductance in the sweat ductal and/or acinar epithelia (sweat chloride, mmol/L, mean ± SEM: 40.0 ± 5.0 [n = 8 samples] and 80.0 ± 3.5 [n = 6 samples]) and airway epithelia (mV, mean ± SEM CFTR-mediated Cl− conductance of 1.2 ± 2.2 [n = 5 studies] and − 6.75 ± 8.1 [n = 4 studies]). These data suggest that the 5T polythymidine tract sequence on specific haplotype backgrounds (TG12 and M470V) may cause a low level of full-length functional CFTR protein and CF-like lung disease.
The Incidence, Correlation with Tumor-Infiltrating Inflammation, and Prognosis of Phosphorylated STAT3 Expression in Human Gliomas
Authors: Mohamed Abou-Ghazal, David S. Yang, Wei Qiao, Chantal Reina-Ortiz, Jun Wei, Ling-Yuan Kong, Gregory N. Fuller, Nobuyoshi Hiraoka, Waldemar Priebe, Raymond Sawaya, Amy B. Heimberger
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in most cancers, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients. We sought to determine the incidence of phosphorylated STAT3 (p-STAT3) expression in malignant gliomas of different pathologic types, whether p-STAT3 expression is a negative prognostic factor, and whether p-STAT3 expression influences the inflammatory response within gliomas. Methods: Using immunohistochemical analysis, we measured the incidence of p-STAT3 expression in 129 patients with gliomas of various pathologic types in a glioma tissue microarray. We categorized our results according to the total number of p-STAT3–expressing cells within the gliomas and correlated this number with the number of infiltrating T cells and T regulatory cells. We then evaluated the association between p-STAT3 expression and median survival time using univariate and multivariate analyses. Results: We did not detect p-STAT3 expression in normal brain tissues or low-grade astrocytomas. We observed significant differences in the incidence of p-STAT3 expression between the different grades of astrocytomas and different pathologic glioma types. p-STAT3 expression was associated with the population of tumor-infiltrating immune cells but not with that of T regulatory cells. On univariate analysis, we found that p-STAT3 expression within anaplastic astrocytomas was a negative prognostic factor. Conclusions: p-STAT3 expression is common within gliomas of both the astrocytic and oligodendroglial lineages and portends poor survival in patients with anaplastic astrocytomas. p-STAT3 expression differs significantly between gliomas of different pathologic types and grades and correlated with the degree of immune infiltration.
Salt-Sensitivity of Proximal Reabsorption Alters Macula Densa Salt and Explains the Paradoxical Effect of Dietary Salt on Glomerular Filtration Rate in Diabetes Mellitus
Authors: Volker Vallon, Dan-Yang Huang, Aihua Deng, Kerstin Richter, Roland C. Blantz, Scott Thomson
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. GFR varies inversely with dietary NaCl in patients with early type I diabetes and in streptozotocin (STZ)-diabetic rats. To explain this paradox within the laws of physiology, it was hypothesized that it results from heightened sensitivity of the diabetic proximal tubule to dietary salt because changes in proximal reabsorption (Jprox) elicit reciprocal adjustments in GFR through the normal actions of tubuloglomerular feedback (TGF). Micropuncture was done in rats after 5 wk of moderately hyperglycemic STZ-diabetes and 1 wk of different NaCl diets. First, single-nephron GFR (SNGFR) and early distal tubular Na+, Cl− and K+ concentration (representing the TGF signal) were measured by collecting from early distal nephrons. In nondiabetics, dietary salt did not affect SNGFR or the TGF signal. In diabetics, the TGF signal varied directly with dietary salt while SNGFR varied inversely with dietary salt. Next, Jprox was measured by collecting from late proximal tubules. To control for different SNGFR, SNGFR was manipulated by perfusing Henle's loop to alter TGF activity. Controlling for SNGFR, dietary salt did not affect Jprox in nondiabetics but exerted a major inverse impact on Jprox in diabetics. In conclusion, normal rats acclimate to dietary NaCl by primarily adjusting transport downstream of the macula densa. In contrast, diabetes renders reabsorption in the proximal tubule sensitive to dietary NaCl with subsequent effects on the TGF signal. This explains the paradoxical effect of dietary NaCl on GFR in early diabetes.