tbuckley/cabot-search huggingface dataset:
Long-term efficacy of tenofovir monotherapy for hepatitis B virus-monoinfected patients after failure of nucleoside/nucleotide analogues
Authors: Florian van Bömmel, Robert A. de Man, Heiner Wedemeyer, Katja Deterding, Jörg Petersen, Peter Buggisch, Andreas Erhardt, Dietrich Hüppe, Kerstin Stein, Jörg Trojan, Christoph Sarrazin, Wulf O. Böcher, Ulrich Spengler, Hermann E. Wasmuth, Jurrien G.P. Reinders, Bernd Möller, Peter Rhode, Heinz-Hubert Feucht, Bertram Wiedenmann, Thomas Berg
Journal: Hepatology (2009)

Tenofovir disoproxil fumarate (TDF) has demonstrated high antiviral efficacy in treatment-naive patients with chronic hepatitis B virus (HBV) infection but experience in nucleoside/nucleotide analogue (NA)-experienced patients is limited. In this retrospective multicenter study we therefore assessed the long-term efficacy of TDF monotherapy in patients with prior failure or resistance to different NA treatments. Criteria for inclusion were HBV DNA levels &gt;4.0 log10 copies/mL at the start and a minimum period of TDF therapy for at least 6 months. In all, 131 patients (mean age 42 ± 12 years, 95 male, 65% hepatitis B e antigen [HBeAg]-positive) were eligible. Pretreatment consisted of either monotherapy with lamivudine (LAM; n = 18), adefovir (ADV; n = 8), and sequential LAM-ADV therapy (n = 73), or add-on combination therapy with both drugs (n = 29). Three patients had failed entecavir therapy. Resistance analysis in 113 of the 131 patients revealed genotypic LAM and ADV resistance in 62% and 19% of patients, respectively. The mean HBV DNA level at TDF baseline was 7.6 ± 1.5 log10 copies/mL. The overall cumulative proportion of patients achieving HBV DNA levels &lt;400 copies/mL was 79% after a mean treatment duration of 23 months (range, 6–60). Although LAM resistance did not influence the antiviral efficacy of TDF, the presence of ADV resistance impaired TDF efficacy (100% versus 52% probability of HBV DNA &lt;400 copies/mL, respectively). However, virologic breakthrough was not observed in any of the patients during the entire observation period. Loss of HBeAg occurred in 24% of patients and HBsAg loss occurred in 3%. No significant adverse events were noticed during TDF monotherapy. Conclusion: TDF monotherapy induced a potent and long-lasting antiviral response in NA-experienced patients with previous treatment failure. Our data may have implications for current add-on strategies. (Hepatology 2009.)
Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD
Authors: L. Puente-Maestu, A. Lazaro, A. Tejedor, S. Camano, M. Fuentes, M. Cuervo, B. O. Navarro, A. Agusti
Journal: Thorax (2010)

<h3>Background</h3> Exhausting exercise reduces the mitochondrial DNA (mtDNA) content in the skeletal muscle of healthy subjects due to oxidative damage. Since patients with chronic obstructive pulmonary disease (COPD) suffer enhanced oxidative stress during exercise, it was hypothesised that the mtDNA content will be further reduced. <h3>Objective</h3> To investigate the effects of exercise above and below the lactate threshold (LT) on the mtDNA content of skeletal muscle of patients with COPD. <h3>Methods</h3> Eleven patients with COPD (67±8 years; forced expiratory volume in 1 s (FEV<sub>1</sub>) 45±8%ref) and 10 healthy controls (66±4 years; FEV<sub>1</sub> 90±7% ref) cycled 45 min above LT (65% peak oxygen uptake (V′o<sub>2</sub>peak) and another 7 patients (65±6 years; FEV<sub>1</sub> 50±4%ref) and 7 controls (56±9 years; FEV<sub>1</sub> 92±6%ref) cycled 45 min below their LT (50% V′o<sub>2</sub>peak). Biopsies from the vastus lateralis muscle were obtained before exercise, immediately after and 1 h, 1 day and 1 week later to determine by PCR the mtDNA/nuclear DNA (nDNA) ratio (a marker of mtDNA content) and the expression of the peroxisome proliferator-activated receptor-γcoactivator-1α (PGC-1α) mRNA and the amount of reactive oxygen species produced during exercise was estimated from total V′o<sub>2</sub>. <h3>Results</h3> Skeletal muscle mtDNA/nDNA fell significantly after exercise above the LT both in controls and in patients with COPD, but the changes were greater in those with COPD. These changes correlated with production of reactive oxygen species, increases in manganese superoxide dismutase and PGC-1α mRNA and returned to baseline values 1 week later. This pattern of response was also observed, albeit minimised, in patients exercising below the LT. <h3>Conclusions</h3> In patients with COPD, exercise enhances the decrease in mtDNA content of skeletal muscle and the expression of PGC-1α mRNA seen in healthy subjects, probably due to oxidative stress.
Cesarean delivery and cow milk allergy/intolerance
Authors: M. Eggesbø, G. Botten, H. Stigum, S. O. Samuelsen, B. Brunekreef, P. Magnus
Journal: Allergy (2005)

The present study provides support for a positive association between cesarean delivery and persistent cow milk allergy/cow's milk intolerance. Correspondingly, a negative association was seen between cesarean delivery and early outgrown cow milk allergy/intolerance. A possible explanation is that cesarean delivery, rather than increasing the overall risk of food allergy, increases the risk of persistency of disease among food allergic children.
Placebo-Controlled, Randomized Clinical Trial of Azimilide for Prevention of Ventricular Tachyarrhythmias in Patients With an Implantable Cardioverter Defibrillator
Authors: Paul Dorian, Martin Borggrefe, Hussein R. Al-Khalidi, Stefan H. Hohnloser, Jose M. Brum, Daljit S. Tatla, Johannes Brachmann, Robert J. Myerburg, David S. Cannom, Michael van der Laan, Michael J. Holroyde, Igor Singer, Craig M. Pratt
Journal: Circulation (2004)

Although implanted cardioverter defibrillators (ICDs) effectively treat sustained ventricular tachyarrhythmias, up to 50% of ICD recipients eventually require concomitant antiarrhythmic drug therapy to prevent symptomatic arrhythmia recurrences and hence reduce the number of device therapies.A total of 633 ICD recipients were enrolled in a randomized, double-blind, placebo-controlled study to evaluate the effect of daily doses of 75 or 125 mg of azimilide on recurrent symptomatic ventricular tachyarrhythmias and ICD therapies. Total all-cause shocks plus symptomatic ventricular tachycardia (VT) terminated by antitachycardia pacing (ATP) were significantly reduced by azimilide, with relative risk reductions of 57% (hazard ratio [HR]=0.43, 95% CI 0.26 to 0.69, P=0.0006) and 47% (HR=0.53, 95% CI 0.34 to 0.83, P=0.0053) at 75- and 125-mg doses, respectively. The reductions in all-cause shocks with both doses of azimilide did not achieve statistical significance. The incidence of all appropriate ICD therapies (shocks or ATP-terminated VT) was reduced significantly among patients taking 75 mg of azimilide (HR=0.52, 95% CI 0.30 to 0.89, P=0.017) and those taking 125 mg of azimilide (HR=0.38, 95% CI 0.22 to 0.65, P=0.0004). Five patients in the azimilide groups and 1 patient in the placebo group had torsade de pointes; all were successfully treated by the device. One patient taking 75 mg of azimilide had severe but reversible neutropenia.Azimilide significantly reduced the recurrence of VT or ventricular fibrillation terminated by shocks or ATP in ICD patients, thereby reducing the burden of symptomatic ventricular tachyarrhythmia.
Randomized Controlled Trial of Entecavir Prophylaxis for Rituximab-Associated Hepatitis B Virus Reactivation in Patients With Lymphoma and Resolved Hepatitis B
Authors: Yi-Hsiang Huang, Liang-Tsai Hsiao, Ying-Chung Hong, Tzeon-Jye Chiou, Yuan-Bin Yu, Jyh-Pyng Gau, Chun-Yu Liu, Muh-Hwa Yang, Cheng-Hwai Tzeng, Pui-Ching Lee, Han-Chieh Lin, Shou-Dong Lee
Journal: Journal of Clinical Oncology (2013)

Purpose The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear. Patients and Methods Eighty patients with CD20 + lymphoma and resolved hepatitis B were randomly assigned to receive either prophylactic entecavir (ETV) before chemotherapy to 3 months after completing chemotherapy (ETV prophylactic group, n = 41) or to receive therapeutic ETV at the time of HBV reactivation and hepatitis B surface antigen (HBsAg) reverse seroconversion since chemotherapy (control group, n = 39). Results Fifty-eight patients (72.5%) were positive for hepatitis B surface antibody, and HBV DNA was undetectable in 50 patients (62.5%). During a mean 18-month follow-up period, one patient (2.4%) in the ETV prophylactic group and seven patients (17.9%) in the control group developed HBV reactivation (P = .027). The cumulative HBV reactivation rates at months 6, 12, and 18 after chemotherapy were 8%, 11.2%, and 25.9%, respectively, in the control group, and 0%, 0%, and 4.3% in the ETV prophylactic group (P = .019). Four patients (50%) in the control group had HBsAg reverse seroconversion after HBV reactivation. The cumulative HBsAg reverse seroconversion rates at months 6, 12, and 18 since chemotherapy were 0%, 6.4%, and 16.3% in the control group, respectively, which were significantly higher than those in the ETV prophylactic group (P = .032). Patients with detectable or undetectable viral load could develop HBV reactivation and HBsAg reverse seroconversion. Conclusion Undetectable HBV viral load before chemotherapy did not confer reactivation-free status. Antiviral prophylaxis can potentially prevent rituximab-associated HBV reactivation in patients with lymphoma and resolved hepatitis B.
Lower Induction of p53 and Decreased Apoptosis in <i>NQO1</i>-Null Mice Lead to Increased Sensitivity to Chemical-Induced Skin Carcinogenesis
Authors: Karim Iskander, Amos Gaikwad, Marilene Paquet, Delwin J. Long, Cory Brayton, Roberto Barrios, Anil K. Jaiswal
Journal: Cancer Research (2005)

Abstract NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic protein that catalyzes metabolic detoxification of quinones and protects cells against redox cycling and oxidative stress. NQO1-null mice deficient in NQO1 protein showed increased sensitivity to 7,12-dimethylbenz(a)anthracene– and benzo(a)pyrene-induced skin carcinogenesis. In the present studies, we show that benzo(a)pyrene metabolite benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide and not benzo(a)pyrene quinones contributed to increased benzo(a) pyrene-induced skin tumors in NQO1-null mice. An analysis of untreated skin revealed an altered intracellular redox state due to accumulation of NADH and reduced levels of NAD/NADH in NQO1-null mice as compared with wild-type mice. Treatment with benzo(a)pyrene failed to significantly increase p53 and apoptosis in the skin of NQO1-null mice when compared with wild-type mice. These results led to the conclusion that altered intracellular redox state along with lack of induction of p53 and decreased apoptosis plays a significant role in increased sensitivity of NQO1-null mice to benzo(a)pyrene-induced skin cancer.
Left bronchial isomerism, normal atrial arrangement and bronchomalacia mimicking asthma: a new syndrome?
Authors: A. Bush
Journal: European Respiratory Journal (1999)

Three children who presented with steroid-resistant airflow obstruction are described. They all had bronchomalacia in the setting of a rare visceral arrangement, namely left bronchial isomerism with normal atrial arrangement. Imaging and, in two cases, a normal residual volume in the face of severe airflow obstruction were diagnostic pointers to a nonasthmatic cause of wheeze. Although the association of these abnormalities may be coincidental, together they may constitute a new clinical syndrome.
CD8+ T-cell responses to different HIV proteins have discordant associations with viral load
Authors: Photini Kiepiela, Kholiswa Ngumbela, Christina Thobakgale, Dhanwanthie Ramduth, Isobella Honeyborne, Eshia Moodley, Shabashini Reddy, Chantal de Pierres, Zenele Mncube, Nompumelelo Mkhwanazi, Karen Bishop, Mary van der Stok, Kriebashnie Nair, Nasreen Khan, Hayley Crawford, Rebecca Payne, Alasdair Leslie, Julia Prado, Andrew Prendergast, John Frater, Noel McCarthy, Christian Brander, Gerald H Learn, David Nickle, Christine Rousseau, Hoosen Coovadia, James I Mullins, David Heckerman, Bruce D Walker, Philip Goulder
Journal: Nature Medicine (2006)
P80 Pre-operative assessment of children undergoing scoliosis surgery
Authors: A. L. R. Russell, S. Charlton, E. R. Mooney, C. Ward, R. I. R. Russell
Journal: Thorax (2010)

<h3>Introduction</h3> Historically, assessment of operative risk in children prior to scoliosis surgery has been largely based on pre-operative lung function testing. Children having scoliosis surgery suffer from a wide range of conditions and many are unable to perform lung function testing. Furthermore, the risk of post-operative ventilation is decreasing suggesting better predictors may be needed. We currently evaluate all such patients, using assessment of airway competency, cough strength, and muscle bulk in estimating the risk of requiring post-operative ventilation. Our data suggest that lung function testing is no longer a good predictor of outcome in this group of patients. <h3>Methods</h3> We retrospectively reviewed the records of 97 patients who have undergone scoliosis surgery between 2004 and 2010. Pulmonary function testing (PFT) was attempted wherever possible. Patients were clinically assessed prior to surgery, and an estimated risk of post-operative ventilation made. Comparison of each method (PFT and clinical assessment) against a primary outcome of requirement for post-operative ventilation, and secondary outcomes of PICU/HDU and hospital length of stay. <h3>Results</h3> PFT was successful in 68/97 (70%) of our patients. One child had an FVC&lt;40% predicted and three children had FVC 40–50% predicted. None of these children required ventilation post-operatively. Of the 14 patients who required post-operative ventilation, pulmonary function testing was only possible for four (FVC range 59%–74% predicted). The remaining 10 who needed ventilation were unable to perform PFT. Clinical assessment of risk was highly accurate in predicting the number of children requiring post-operative ventilation in all groups (Abstract P80 Table 1). <h3>Conclusions</h3> The group of patients who are most likely to require post-operative ventilation are poor candidates for pulmonary function testing. To assess these children we need to take account of other factors which are important for their respiratory function post-operatively. Clinical assessment of risk can be highly accurate in predicting the need for ventilation following scoliosis surgery.
Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF
Authors: Teruya Nakamura, Shinya Mizuno, Kunio Matsumoto, Yoshiki Sawa, Hikaru Matsuda, Toshikazu Nakamura
Journal: Journal of Clinical Investigation (2000)

Using a rat model of ischemia/reperfusion injury, we demonstrate here that HGF is cardioprotective due to its antiapoptotic effect on cardiomyocytes. Following transient myocardial ischemia and reperfusion, c-Met/HGF receptor expression rapidly increased in the ischemic myocardium, an event accompanied by a dramatic increase in plasma HGF levels in the infarcted rats. When endogenous HGF was neutralized with a specific antibody, the number of myocyte cell deaths increased markedly, the infarct area expanded, and the mortality increased to 50%, as compared with a control group in which there was no mortality. Plasma from the myocardial infarcted rats had cardioprotective effects on primary cultured cardiomyocytes, but these effects were significantly diminished by neutralizing HGF. In contrast, recombinant HGF administration reduced the size of infarct area and improved cardiac function by suppressing apoptosis in cardiomyocytes. HGF rapidly augmented Bcl-xL expression in injured cardiomyocytes both in vitro and in vivo. As apoptosis of cardiomyocytes is one of the major contributors to the pathogenesis in subjects with ischemia/reperfusion injury, prevention of apoptosis may prove to be a reasonable therapeutic strategy. Supplements of HGF, an endogenous cardioprotective factor, may be found clinically suitable in treating subjects with myocardial infarction.
IT-05 * ADMINISTRATION OF TOCA 511 TO SUBJECTS WITH RECURRENT HGG UNDERGOING REPEAT RESECTION
Authors: T. F. Cloughesy, S. Kesari, S. Kalkanis, T. Mikkelsen, J. Landolfi, J. B. Elder, L. M. Liau, C. C. Chen, S. Bloomfield, D. Piccioni, E. A. Chiocca, G. Foltz, J. M. Robbins, D. Ostertag, D. J. Jolly, C. Ibanez, D. Pertschuk, C. Pan, M. A. Vogelbaum
Journal: Neuro-Oncology (2014)

INTRODUCTION: Recurrent high grade glioma (rHGG) remains one of the most deadly cancers. Investigational agents Toca 511, a retroviral replicating vector, and Toca FC (extended-release 5-FC) are used in combination to target residual tumor at the time of resection. METHODS: This study (NCT01470794) is primarily designed to identify the highest safe and well tolerated dose of Toca 511 administered to subjects undergoing resection for rHGG. The starting dose was 1.4x10^7 Transducing Units (TU). Using a standard 3 + 3 design, doses have been escalated at half-log intervals to 4.8x10^9 TU. Following tumor resection, multiple injections of vector are administered into the walls of the resection cavity. Starting approximately 6 weeks post-surgery cyclic oral Toca FC is administered. RESULTS: 36 patients across 6 vector dose cohorts have been studied. In evaluable patients the largest cross-sectional area of tumor ranged from 0 (unmeasurable) to 14.57 cm2. The combination treatment has been safe and well tolerated with 1 grade 3 possibly treatment related AE of transient generalized weakness. Subsequent resection of tumor from subjects who previously received Toca 511 confirmed virus can selectively infect residual tumor cells. Preliminary data based on investigator assessment show 14/32 evaluable patients achieved best overall response of SD or better (from baseline MRI 5-7 weeks post-surgery, prior to 5-FC). Treatment related pseudoprogression has been observed by MRI and supported by histopathology of re-resected tumor. Independently reviewed response data and PFS will be presented. The median survival by Kaplan Meier analysis in the first 4 cohorts is 11.8 months. CONCLUSION: Toca 511 administered at the time of tumor resection and followed by cycles of Toca FC has been safe and well tolerated to date. In addition to continued dose escalation of Toca 511 and Toca FC in patients with rHGG, a randomized trial in patients with newly diagnosed glioma is now planned.
Can irradiation destroy metastatic pelvic lymph nodes?
Authors: F. Rutlege
Journal: JAMA (1965)

That irradiation is ineffective in the control of nodal metastases from cervical carcinoma is a cherished belief of some authorities, particularly those who prefer surgical treatment. This belief, however, is largely based on experience with the older methods of x-ray treatment, methods which are inadequate by modern standards. Today, an increasing amount of evidence indicates that, with apparatus now available, a cancerocidal dose of irradiation can indeed be delivered to the pelvic nodes. The opinion that irradiation was ineffective was formed from two observations: (1) Pelvic nodes excised after irradiation treatment sometimes contain metastatic foci; (2) The first sign of recurrence was often a palpable pelvic node for patients who were treated by irradiation and who did not have anykind of surgical treatment. The inference was that the radiosensitive primary lesion was destroyed, but the nodal disease was not radiosensitive, and therefore, was not destroyed. There was, also, evidence,
Amelioration of myocarditis by HVEM-overexpressing dendritic cells through induction of IL-10-producing cells
Authors: Gang Cai, Huaizhou Wang, Qin Qin, Jun Zhang, Zhi Zhu, Menglei Liu, Qian Shen
Journal: Cardiovascular Research (2009)

AimsHerpes virus entry mediator (HVEM) is considered to be a molecular 'switch' for immune responses, and a role in immune modification has been reported. The aim of this study was to assess whether HVEM-mediated immune suppression could protect against experimental autoimmune myocarditis (EAM) induced by myosin.
Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dysfunction during reperfusion
Authors: Z.-Q. Zhi-Qing Zhao, Cullen D. Morris, Jason M. Budde, N.-P. Ning-Ping Wang, Satoshi Muraki, H.-Y. He-Ying Sun, Robert A. Guyton
Journal: Cardiovascular Research (2003)

Objective: Myocardial apoptosis is primarily triggered during reperfusion (R) through various mechanisms that may involve endonuclease to cleavage genomic DNA in the internucleosomal linker regions. However, the relative contribution of myocardial apoptosis to development of myocardial injury during R remains unknown. In the present study, we examined whether inhibition of apoptosis with aurintricarboxylic acid (ATA), an endonuclease inhibitor, during R reduces infarct size and improves regional contractile function. Methods and Results: In two groups of chronically-instrumented dogs, 1 h of left anterior descending (LAD) coronary occlusion was followed by 24 h of R with infusion of saline (control, n = 8) or ATA (1 mg/kg/h, n = 8) into the left atrium starting 5 min before R and continuing for 2 h. ATA significantly reduced apoptotic cells (TUNEL staining) in the peri-necrotic myocardium (12±1%* vs. 36±4%), consistent with the absence of DNA laddering. To confirm inhibition of apoptosis with ATA, densitometrically, Bcl-2 (% of normal myocardium) was significantly increased vs. control (102±12* vs. 68±9) and Bax as well as the activated caspase-3 were significantly reduced vs. control (108±17* vs. 194±42 and −29±4* vs. 174±43, respectively). ATA significantly improved segmental shortening (3.3±1.2* vs. −1.8±0.7%) and segmental work (79.3±11.3* vs. 7.1±5.8 mmHg/mm) in area at risk myocardium, and reduced infarct size (TTC staining, 27±0.2* vs. 37±0.5%), confirmed by lower plasma creatine kinase activity. In addition, myocardial blood flow (0.9±0.1* vs. 0.4±0.1 ml/min/g) and endothelial-dependent maximal vascular relaxation (119±6* vs. 49±8%) were significantly improved. Myeloperoxidase activity in area at risk myocardium, a marker for neutrophil accumulation, was also significantly reduced (17±4* vs. 138±28 ΔAbs/min). Conclusions: These data suggest that the inhibition of apoptosis during R is associated with a reduction in infarction, improvement in regional contractile and vascular endothelial functions as well as augmentation in myocardial blood flow. *P<0.05 vs. control group.