tbuckley/cabot-search huggingface dataset:
Preoperative F-18 Fluorodeoxyglucose-Positron Emission Tomography Maximal Standardized Uptake Value Predicts Survival After Lung Cancer Resection
Authors: Robert J. Downey, Timothy Akhurst, Mithat Gonen, Alain Vincent, Manjit S. Bains, Steven Larson, Valerie Rusch
Journal: Journal of Clinical Oncology (2004)

A retrospective review of surgically treated lung cancer patients imaged preoperatively by F-18 fluorodeoxyglucose-positron emission tomography ([(18)F]FDG-PET) to determine if the primary tumor standardized uptake value (SUV) predicts survival.Non-small-cell lung cancer or carcinoid pT1-4, N0-2, M0 patients treated by R0 surgical resection alone were imaged with computed tomography scan and PET within 90 days before surgery. Prognostic variables were assessed by log-rank test; survival was assessed by the method of Kaplan and Meier.One hundred consecutive patients (48 men, 52 women) were retrospectively reviewed. Median follow-up for surviving patients was 28 months (range, 16 to 81 months). Median maximal SUV (SUV(MAX)) was 9. The 2-year survival for patients with SUV(MAX) more than 9 was 68% and for those with SUV(MAX) less than 9, it was 96% (P <.01, log-rank test). In a multivariate analysis including pathologic tumor size, involved nodes, histology, and SUV(MAX), only tumor size (T) more than 3 cm and SUV(MAX) more than 9 and their interaction were significant predictors of survival (P =.01, 0.02, and < 0.01, respectively). The 3-year survivals for patients with both T less than 3 cm and SUV(MAX) less than 9 was 97%; for those with T less than 3 cm and SUV(MAX) more than 9, it was 94%; for those with T more than 3 cm and SUV(MAX) less than 9, it was 93%; and for those with T more than 3 cm and SUV(MAX) more than 9, it was 47% (P <.01).In surgically managed lung cancer patients, SUV is a predictor of overall survival after resection. The addition of SUV(MAX) to pathologic tumor size identifies a subgroup of patients at highest risk for death as a result of recurrent disease after resection.
Adaptive Response to a Low-Protein Diet in Predialysis Chronic Renal Failure Patients
Authors: JACQUES BERNHARD, BERNARD BEAUFRE[Combining Grave Accent]RE, MAURICE LAVILLE, DENIS FOUQUE
Journal: Journal of the American Society of Nephrology (2001)

Abstract. A randomized, controlled study of 12 patients with mild chronic renal failure was designed to assess the metabolic effects of a low-protein diet supplemented (n = 6) or not (n = 6) with ketoanalogs of amino acids. The protein intake was prescribed so that both groups were isonitrogenous. The dietary survey each month included a 3-d food record and a 24-h urine collection for urea measurement. After a 4- to 6-wk equilibrium period (standard occidental diet, 1.11 g of protein and 32 kcal/kg per d), patients reduced their protein intake to reach 0.71 g of protein/kg per d during the third month. Energy intake was kept constant (31 kcal/kg per d) during the 3-mo period. Compliance to the diet was achieved after 2 mo of training. Leucine turnover measurement was performed before and at the end of the 3-mo low-protein period. There was no clinical change, whereas total body flux decreased by 8% (P < 0.05) and leucine oxidation by 18% (P < 0.05). No difference could be attributed to the ketoanalogs themselves. Thus, under sufficient energy intake, a low-protein diet is nutritionally and metabolically safe during chronic renal failure. The nitrogen-sparing effect of a low-protein diet is still present during mild chronic renal insufficiency.
Lung Volume Reduction Surgery and Improvement of Endothelial Function and Blood Pressure in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial
Authors: Christian F. Clarenbach, Noriane A. Sievi, Matthias Brock, Didier Schneiter, Walter Weder, Malcolm Kohler
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Preliminary studies have shown that both airflow obstruction and systemic inflammation may contribute to endothelial dysfunction in COPD. Lung volume reduction surgery (LVRS) is a treatment option in selected patients with COPD with emphysema that improves breathing mechanics and lung function.Objectives: To determine the effect of LVRS on endothelial function and systemic inflammation.Methods: We conducted a randomized controlled trial in 30 patients scheduled for LVRS. In the intervention group, immediate LVRS was performed after baseline evaluation followed by reassessment 3 months later. In the control group, reassessment followed 3 months after baseline evaluation, and thereafter LVRS was performed.Measurements and Main Results: The primary outcome measures were the treatment effect on endothelial function and systemic inflammation. In the LVRS group 14 patients completed the trial and 13 in the control group. LVRS led to a relative reduction in mean (SD) residual volume/total lung capacity of −12% (12%) and an increase in FEV1 of 29% (27%). Flow-mediated dilatation of the brachial artery increased in the intervention group as compared with the control group (+2.9%; 95% confidence interval, +2.1 to +3.6%; P < 0.001), whereas there was no significant change in systemic inflammation. A significant treatment effect on mean blood pressure was observed (−9.0 mm Hg; 95% confidence interval, −17.5 to −0.5; P = 0.039).Conclusions: Endothelial function and blood pressure are improved 3 months after LVRS in patients with severe COPD and emphysema. LVRS may therefore have beneficial effects on cardiovascular outcomes.Clinical trial registered with www.clinicaltrials.gov (NCT 01020344).
Cooperative Trial CWS-91 for Localized Soft Tissue Sarcoma in Children, Adolescents, and Young Adults
Authors: Tobias M. Dantonello, Christoph Int-Veen, Dieter Harms, Ivo Leuschner, Bernhard F. Schmidt, Manfred Herbst, Heribert Juergens, Hans-Gerhard Scheel-Walter, Stefan S. Bielack, Thomas Klingebiel, Roswitha Dickerhoff, Sylvia Kirsch, Ines Brecht, Rainer Schmelzle, Michael Greulich, Helmut Gadner, Jeanette Greiner, Ildiko Marky, Joern Treuner, Ewa Koscielniak
Journal: Journal of Clinical Oncology (2009)

To improve risk-adapted therapy for localized childhood soft tissue sarcoma within an international multicenter setting.Four hundred forty-one patients younger than 21 years with localized rhabdomyosarcoma and rhabdomyosarcoma-like tumors (ie, extraosseous tumors of the Ewing family, synovial sarcoma, and undifferentiated sarcoma) were eligible. Therapy was stratified according to postsurgical stage, histology, and tumor site. In unresectable tumors, treatment was further adapted depending on response to induction chemotherapy, TN classification, tumor size and second-look surgery. A novel five-drug combination of etoposide, vincristine, dactinomycin, ifosfamide, and doxorubicin (EVAIA) was evaluated for high-risk patients, but cumulative chemotherapy dosage and treatment duration were reduced for the remaining individuals as compared with that of the previous trial CWS-86. Hyperfractionated accelerated radiotherapy (HART) was recommended at doses of either 32 or 48 Gy.At a median follow-up of 8 years, 5-year event-free survival (EFS) and overall (OS) survival for the entire cohort was 63% +/- 4% and 73% +/- 4%, respectively (all survival rates in this abstract are calculated and displayed with +/-95% CI). EFS/OS rates by histology were 60% +/- 5%/72% +/- 5% in rhabdomyosarcoma, 62% +/- 10%/69% +/- 10% for Ewing tumors of soft tissues, 84% +/- 12%/90% +/- 10% for synovial sarcoma, and 67% +/- 38%/83% +/- 30% for undifferentiated sarcoma, respectively. Response to one cycle of the five-drug combination EVAIA was similar to that of the four-drug combination VAIA used in CWS-86. Two hundred twelve patients with rhabdomyosarcoma underwent radiation (EFS, 66% +/- 6%); 53 of those patients had a favorable risk profile and received 32 Gy of HART (EFS, 73% +/- 12%). TN classification, tumor site, tumor size, histology, and age were prognostic in univariate analysis.Improved risk stratification enabled decreased therapy intensity for selected patients without compromising survival. Intensified chemotherapy with EVAIA did not improve outcome of localized high-risk rhabdomyosarcoma.
A Cellular Mechanism for the Generation of Ventricular Arrhythmias by Acetylstrophanthidin
Authors: GREGORY R. FERRIER, JAMES H. SOUNDERS, CARLOS MENDEZ
Journal: Circulation Research (1973)

Transmembrane activity was recorded from canine false tendons bathed with Tyrode's solution at 37°C. Stimulus patterns provided a 3-second pause after every ten beats. Acetylstrophanthidin was infused at concentrations up to 2x10 -7 g/ml. One or two transient depolarizations (TDs) followed the last driven response of each series. The appearance of TDs was associated with depression of normal phase-4 depolarization. The peak of the earliest TD (TD-1) occurred at an interval approximately equal to the basic cycle length. The later TD (TD-2) occurred at about twice the basic cycle length. Coupling intervals were determined primarily by the last cycle length. The amplitude of TD-1 was maximal when the basic cycle length was 600 msec, but TD-2 continued to increase as the basic cycle length diminished further. The amplitude of both TDs increased with the number of beats in the train. Either or both could reach threshold and induce single extrasystoles or trains of extrasystoles. TDs could be induced to reach threshold after each driven response, resulting in sustained bigeminal rhythms with fixed coupling. Possibly TDs provide a mechanism for various clinically observed arrhythmias induced by cardiac glycosides.
T Cell–specific Inactivation of the Interleukin 10 Gene in Mice Results in Enhanced T Cell Responses but Normal Innate Responses to Lipopolysaccharide or Skin Irritation
Authors: Axel Roers, Lisa Siewe, Elke Strittmatter, Martina Deckert, Dirk Schlüter, Werner Stenzel, Achim D. Gruber, Thomas Krieg, Klaus Rajewsky, Werner Müller
Journal: The Journal of Experimental Medicine (2004)

Interleukin (IL)-10 is a regulator of inflammatory responses and is secreted by a variety of different cell types including T cells. T regulatory cells have been shown to suppress immune responses by IL-10–dependent, but also IL-10–independent, mechanisms. Herein, we address the role of T cell–derived IL-10 in mice with an inactivation of the IL-10 gene restricted to T cells generated by Cre/loxP-mediated targeting of the IL-10 gene. Splenocytes from this T cell–specific mutant secrete increased amounts of proinflammatory cytokines after activation in vitro compared with show enhanced contact hypersensitivity reactions, and succumb to severe immunopathology upon infection with Toxoplasma gondii. Despite intact IL-10 genes in other cell types, the dysregulation of T cell responses observed in the T cell–specific IL-10 mutant closely resembles the phenotype in complete IL-10 deficiency. However, in contrast to complete IL-10 deficiency, sensitivity to endotoxic shock and irritant responses of the skin are not enhanced in the T cell–specific IL-10 mutant. Our data highlight the importance of T cell–derived IL-10 in the regulation of T cell responses and demonstrate that endotoxic shock and the irritant response of the skin are controlled by IL-10 from other cell types.
Geriatrics: The Diseases of Old Age and Their Treatment
Authors: A Mark Clarfield
Journal: BMJ (2007)

Geriatrics has a long and fascinating history, going back to the epic of Gilgamesh, through the Jewish Bible and up to the 19th century studies of Jean-Marie Charcot. However, many believe that the field entered the modern era with the publication in 1914 of Ignatz Leo Nascher's seminal text. The book's origins are interesting in that it began with a ward round. As a medical student in New York, Nascher was part of a team that came to an acutely ill woman, whose condition Nascher's professor described in words that can still be heard today: “Old age.” When our young hero asked what could be done to help the patient, he was shocked by his teacher's response: “Nothing!”

Several years later Nascher wrote his definitive text, in which he first formulated the clumsy term …
Cytomegalovirus reactivation and mortality in patients with acute respiratory distress syndrome
Authors: David S. Y. Ong, Cristian Spitoni, Peter M. C. Klein Klouwenberg, Frans M. Verduyn Lunel, Jos F. Frencken, Marcus J. Schultz, Tom van der Poll, Jozef Kesecioglu, Marc J. M. Bonten, Olaf L. Cremer
Journal: Intensive Care Medicine (2015)

Cytomegalovirus (CMV) reactivation occurs frequently in patients with the acute respiratory distress syndrome (ARDS) and has been associated with increased mortality. However, it remains unknown whether this association represents an independent risk for poor outcome. We aimed to estimate the attributable effect of CMV reactivation on mortality in immunocompetent ARDS patients. We prospectively studied immunocompetent ARDS patients who tested seropositive for CMV and remained mechanically ventilated beyond day 4 in two tertiary intensive care units in the Netherlands from 2011 to 2013. CMV loads were determined in plasma weekly. Competing risks Cox regression was used with CMV reactivation status as a time-dependent exposure variable. Subsequently, in sensitivity analyses we adjusted for the evolution of disease severity until onset of reactivation using marginal structural modeling. Of 399 ARDS patients, 271 (68 %) were CMV seropositive and reactivation occurred in 74 (27 %) of them. After adjustment for confounding and competing risks, CMV reactivation was associated with overall increased ICU mortality (adjusted subdistribution hazard ratio (SHR) 2.74, 95 % CI 1.51–4.97), which resulted from the joint action of trends toward an increased mortality rate (direct effect; cause specific hazard ratio (HR) 1.58, 95 % CI 0.86–2.90) and a reduced successful weaning rate (indirect effect; cause specific HR 0.83, 95 % CI 0.58–1.18). These associations remained in sensitivity analyses. The population-attributable fraction of ICU mortality was 23 % (95 % CI 6–41) by day 30 (risk difference 4.4, 95 % CI 1.1–7.9). CMV reactivation is independently associated with increased case fatality in immunocompetent ARDS patients who are CMV seropositive.
American Joint Committee on Cancer Tumor–Node–Metastasis Stage After Neoadjuvant Chemotherapy and Breast Cancer Outcome
Authors: Lisa A. Carey, Richard Metzger, E. Claire Dees, Frances Collichio, Carolyn I. Sartor, David W. Ollila, Nancy Klauber-DeMore, Jan Halle, Lynda Sawyer, Dominic T. Moore, Mark L. Graham
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Response to neoadjuvant chemotherapy is used as an intermediate endpoint for breast cancer relapse and survival. Most breast cancer response classification systems use pathologic complete response, either alone or in conjunction with clinical assessments, to categorize response. We examined the ability of the revised 2003 American Joint Committee on Cancer (AJCC) tumor–node–metastasis (TNM) staging system, which considers both the number of involved axillary lymph nodes and the extent of tumor in the breast to predict patient survival after neoadjuvant chemotherapy for breast cancer. Methods: We assessed the pathologic stage of residual tumor in 132 patients with nonmetastatic breast cancer after they had undergone neoadjuvant chemotherapy and examined the association between AJCC TNM stage and subsequent distant disease–free survival and overall survival. All statistical tests were two-sided. Results: At a median follow-up of 5 years, pathologic stage in the surgical specimens after neoadjuvant chemotherapy using the revised AJCC system was strongly associated with both distant disease–free survival and overall survival. A higher pathologic stage of residual tumor after neoadjuvant chemotherapy was associated with a statistically significant lower rate of distant disease–free survival (stage 0: 95%, stage I: 84%, stage II: 72%, and stage III: 47%; Ptrend <.001). The 5-year distant disease–free survival for patients with residual stage IIIC tumors was only 18% (95% CI = 0% to 36%). Conclusion: Classification of residual tumor in the breast and axillary surgical specimens after neoadjuvant chemotherapy using the revised AJCC TNM system is useful for predicting distant relapse and survival.
The Origin and Evolution of Variable-Region Helices in V4 and V7 of the Small- Subunit Ribosomal RNA of Branchiopod Crustaceans
Authors: T J Crease, D J Taylor
Journal: Molecular Biology and Evolution (1998)

We sequenced the V4 and V7 regions of the small-subunit ribosomal RNA (SSU rRNA) from 38 species of branchiopod crustaceans (e.g., Artemia, Daphnia, Triops) representing all eight extant orders. Ancestral large-bodied taxa in the orders Anostraca, Notostraca, Laevicaudata, and Spinicaudata (limnadiids and cyzicids) possess the typical secondary structure in these regions, whereas the spinicaudatan Cyclestheria and all of the cladocerans (Anomopoda, Ctenopoda, Onychopoda, and Haplopoda) possess three unique helices. Although the lengths and primary sequences of the distal ends of these helices are extremely variable, their locations, secondary structures, and primary sequences at the proximal end are conserved, indicating that they are homologous. This evidence supports the classical view that Cladocera is a monophyletic group and that the cyclestheriids are transitional between spinicaudatans and cladocerans. The single origin and persistence since the Permian of the unique cladoceran helices suggests that births and deaths of variable region helices have been rare. The broad range of sequence divergences observed among the cladoceran helices permitted us to make inferences about their evolution. Although their proximal ends are very GC-biased, there is a significant negative correlation between length and GC content due to an increasing proportion of U at their distal ends. Slippage-like processes occurring at unpaired nucleotides or bulges, which are very U-biased, are associated with both helix origin and runaway length expansion. The overall GC contents and lengths of V4 and V7 are highly correlated. More surprisingly, the lengths of these SSU rRNA variable regions are also highly correlated with the length of the large-subunit rRNA expansion segment, D2, indicating that mechanisms affecting length variation do so both across single genes and across genes in the rRNA gene family.
Direct effects of thyrotropin-releasing hormone, cyproheptadine, and dopamine on adrenocorticotropin secretion from human corticotroph adenoma cells in vitro.
Authors: M Ishibashi, T Yamaji
Journal: Journal of Clinical Investigation (1981)

In an attempt to delineate the mechanism and the site of action of cyproheptadine and dopaminergic agonists as well as hormones including thyrotropin-releasing hormone (TRH) and hydrocortisone, the effects of these substances on ACTH secretion from corticotroph adenoma cells in culture were examined. Dispersed cells of pituitary adenomas obtained at surgery from four patients with Nelson's syndrome and one subject with Cushing's disease formed a monolayer and actively secreted ACTH into the medium. When TRH (0.1 microM) was added to the medium, a significant increase in ACTH secretion was demonstrated by adenoma cells from two patients who responded to TRH preoperatively. Moreover, a dose-response relationship between TRH concentrations and ACTH secretion was observed. Incubation of cells with cyproheptadine (1 or 0.1 microM) resulted in a significant decrease in ACTH release, and inhibited stimulation produced by TRH in one experiment. This effect of cyproheptadine was blocked when equimolar concentrations of serotonin was coincubated, whereas serotonin by itself did not affect ACTH secretion. Dopamine (0.1 microM) lowered ACTH accumulation in the medium, which was blocked by the addition of haloperidol. When hydrocortisone was added to the culture, dose-dependent suppression of ACTH secretion was demonstrated. TRH at an equimolar concentration reversed this effect, but, failed to overcome the inhibition induced by a higher concentration of hydrocortisone in cells from one adenoma studied. Cultured normal corticotrophs obtained from a patient with metastatic breast cancer, on the other hand, did not show any response to these substances, except for hydrocortisone. We suggest that TRH, cyproheptadine, dopamine affect ACTH secretion in patients with ACTH-producing pituitary adenomas by their direct action on the adenoma.
Genome-wide association study identifies two susceptibility loci for osteosarcoma
Authors: Sharon A Savage, Lisa Mirabello, Zhaoming Wang, Julie M Gastier-Foster, Richard Gorlick, Chand Khanna, Adrienne M Flanagan, Roberto Tirabosco, Irene L Andrulis, Jay S Wunder, Nalan Gokgoz, Ana Patiño-Garcia, Luis Sierrasesúmaga, Fernando Lecanda, Nilgün Kurucu, Inci Ergurhan Ilhan, Neriman Sari, Massimo Serra, Claudia Hattinger, Piero Picci, Logan G Spector, Donald A Barkauskas, Neyssa Marina, Silvia Regina Caminada de Toledo, Antonio S Petrilli, Maria Fernanda Amary, Dina Halai, David M Thomas, Chester Douglass, Paul S Meltzer, Kevin Jacobs, Charles C Chung, Sonja I Berndt, Mark P Purdue, Neil E Caporaso, Margaret Tucker, Nathaniel Rothman, Maria Teresa Landi, Debra T Silverman, Peter Kraft, David J Hunter, Nuria Malats, Manolis Kogevinas, Sholom Wacholder, Rebecca Troisi, Lee Helman, Joseph F Fraumeni, Meredith Yeager, Robert N Hoover, Stephen J Chanock
Journal: Nature Genetics (2013)
Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection
Authors: Nezam Afdhal, K. Rajender Reddy, David R. Nelson, Eric Lawitz, Stuart C. Gordon, Eugene Schiff, Ronald Nahass, Reem Ghalib, Norman Gitlin, Robert Herring, Jacob Lalezari, Ziad H. Younes, Paul J. Pockros, Adrian M. Di Bisceglie, Sanjeev Arora, G. Mani Subramanian, Yanni Zhu, Hadas Dvory-Sobol, Jenny C. Yang, Phillip S. Pang, William T. Symonds, John G. McHutchison, Andrew J. Muir, Mark Sulkowski, Paul Kwo
Journal: New England Journal of Medicine (2014)

Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need.We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea.Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment. (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).