tbuckley/cabot-search huggingface dataset:
Phase II Study of Everolimus (RAD001) in Previously Treated Small Cell Lung Cancer
Authors: Ahmad Tarhini, Athanasios Kotsakis, William Gooding, Yongli Shuai, Daniel Petro, David Friedland, Chandra P. Belani, Sanja Dacic, Athanassios Argiris
Journal: Clinical Cancer Research (2010)

Mammalian target of rapamycin (mTOR) is a promising target in small cell lung cancer (SCLC). We designed a phase II study of everolimus, an mTOR inhibitor, in previously treated, relapsed SCLC.Patients were treated with everolimus 10 mg orally daily until disease progression. The primary endpoint was disease control rate (DCR) at 6 weeks. PI3K/Akt signaling pathway biomarkers were evaluated on baseline tumor tissue.A total of 40 patients were treated: 23 had 1 prior regimen/sensitive relapse, 4 had 1 prior regimen/refractory, and 13 had 2 prior regimens. Twenty-eight patients received 2 or more cycles of everolimus, 7 received 1 cycle, and 5 did not complete the first cycle. Best response in 35 evaluable patients: 1 (3%) partial response (in sensitive relapse), 8 (23%) stable disease, and 26 (74%) progression; DCR at 6 weeks was 26% (95% CI = 11-40). Median survival was 6.7 months and median time to progression was 1.3 months. Grade 3 toxicities included thrombocytopenia (n = 2), neutropenia (n = 2), infection (n = 2), pneumonitis (n = 1), fatigue (n = 1), elevated transaminases (n = 1), diarrhea (n = 2), and acute renal failure (n = 1). High phosphorylated AKT expression was modestly associated with overall survival (HR = 2.07; 95% CI = 0.97-4.43). Baseline S6 kinase protein expression was significantly higher in patients with disease control versus patients with progression (P = 0.0093).Everolimus was well tolerated but had limited single-agent antitumor activity in unselected previously treated patients with relapsed SCLC. Further evaluation in combination regimens for patients with sensitive relapse may be considered.
Acute Respiratory Distress Syndrome in Critically Ill Patients With Severe Acute Respiratory Syndrome
Authors: Thomas W K Lew, Tong-Kiat Kwek, Dessmon Tai, Arul Earnest, Shi Loo, Kulgit Singh, Kim Meng Kwan, Yeow Chan, Chik Foo Yim, Siam Lee Bek, Ai Ching Kor, Wee See Yap, Y Rubuen Chelliah, Yeow Choy Lai, Soon-Keng Goh
Journal: JAMA (2003)

Severe acute respiratory syndrome (SARS) is an emerging infectious disease with a 25% incidence of progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mortality exceeding 10%.To describe the clinical spectrum and outcomes of ALI/ARDS in patients with SARS-related critical illness.Retrospective case series of adult patients with probable SARS admitted to the intensive care unit (ICU) of a hospital in Singapore between March 6 and June 6, 2003.The primary outcome measure was 28-day mortality after symptom onset.Of 199 patients hospitalized with SARS, 46 (23%) were admitted to the ICU, including 45 who fulfilled criteria for ALI/ARDS. Mortality at 28 days for the entire cohort was 20 (10.1%) of 199 and for ICU patients was 17 (37%) of 46. Intensive care unit mortality at 13 weeks was 24 (52.2%) of 46. Nineteen of 24 ICU deaths occurred late (> or =7 days after ICU admission) and were attributed to complications related to severe ARDS, multiorgan failure, thromboembolic complications, or septicemic shock. ARDS was characterized by ease of derecruitment of alveoli and paucity of airway secretion, bronchospasm, or dynamic hyperinflation. Lower Acute Physiology and Chronic Health Evaluation II scores and higher baseline ratios of PaO2 to fraction of inspired oxygen were associated with earlier recovery.Critically ill patients with SARS and ALI/ARDS had characteristic clinical findings, high rates of complications; and high mortality. These findings may provide useful information for optimizing supportive care for SARS-related critical illness.
Lung Cancer After Hodgkin’s Disease: A Nested Case-Control Study of the Relation to Treatment
Authors: A. J. Swerdlow, M. J. Schoemaker, R. Allerton, A. Horwich, J. A. Barber, D. Cunningham, T. A. Lister, A. Z.S. Rohatiner, G. Vaughan Hudson, M. V. Williams, D. C. Linch
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To investigate the causes of the raised risk of lung cancer in patients who have had Hodgkin’s disease, and in particular the relationship to treatment. PATIENTS AND METHODS: A nested case-control study was conducted within a cohort of 5,519 patients with Hodgkin’s disease treated in Britain during 1963 through 1993. For 88 cases of lung cancer and 176 matched control subjects, information on treatment and other risk factors was extracted from hospital case-notes, and odds ratios for lung cancer in relation to these factors were calculated. RESULTS: Risk of lung cancer was borderline significantly greater in patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy than those who did not receive this treatment (relative risk [RR] = 1.66; 95% confidence interval [CI], 0.99 to 2.82), and increased with number of cycles of MOPP (P = .07). Exclusion of lung cancers for which histologic confirmation was not available strengthened these associations (RR = 2.41; 95% CI, 1.33 to 4.51; P = .004 for any MOPP and P = .007 for trend with number of cycles of MOPP). Risks were not raised, however, after chlorambucil, vinblastine, procarbazine, and prednisone treatment. There was evidence that the raised risk of lung cancer occurring in relation to radiotherapy was restricted to histologies other than adenocarcinoma. CONCLUSION: The results suggest that MOPP chemotherapy may lead to elevated risk of lung cancer, at least in certain subgroups of patients. The role of chemotherapy in the etiology of lung cancer after Hodgkin’s disease deserves further investigation.
The Cypher stent: no longer efficacious at three months in the porcine model?
Authors: A LAFONT
Journal: Cardiovascular Research (2004)

See article by Carter et al.  [2]  (pages 617–624) in this issue .

Drug-eluting stents have represented one of the most exciting, innovative technologies, and the 0% restenosis rate has led to overwhelming enthusiasm in the medical world, even if a careful examination of the results did not show any effect on the occurrence of death and acute myocardial infarction [1]. The study of Carter et al. [2] in this issue of Cardiovascular Research brings a key message that tempers our enthusiasm, since they surprisingly discovered that, in the pig model, the Cypher stent failed to reduce restenosis at 3 and 6 months. Moreover, although the drug is still present, there is more smooth muscle cell proliferation and inflammation with the Cypher stent than with the bare stent. Since the study was conducted by Robert Falotico, the “father” of the Cypher stent [3], there is no doubt regarding the validity of these data. This initiates a huge controversy: now the question is, how is this possible? The primary suspect is the anti-restenosis strategy, i.e., inhibition of smooth muscle cell proliferation via the cell cycle [4]. Impairing the healing may not automatically mean that the reaction to the injury process is definitely abolished … 

*Fax: +33 1 5609 2664. Email address: antoine.lafont{at}egp.ap-hop-paris.fr
Neutralization of endogenous tumor necrosis factor ameliorates the severity of myosin-induced myocarditis.
Authors: S C Smith, P M Allen
Journal: Circulation Research (1992)

Tumor necrosis factor (TNF) and interferon gamma (IFN-gamma) are pluripotent cytokines and have multiple functions during the inflammatory response. Using a murine model of autoimmune myocarditis, we studied the role of TNF and IFN-gamma in myocardial inflammation. Neutralizing monoclonal antibodies against TNF-alpha/beta and IFN-gamma were administered to myosin-immunized A/J mice to assess the effect on the severity of myocardial inflammation. Anti-TNF treatment significantly reduced the severity of myocarditis compared with rat immunoglobulin G or saline controls (p less than 0.0007) when given before myosin immunization. Myosin-specific lymph node T-cell proliferation studies showed no difference in the proliferative response between the anti-TNF-treated mice and controls. Administration of anti-TNF to mice after myosin immunization had no effect on the severity of inflammation. This suggests that TNF is an important mediator early in the pathogenesis of myocardial inflammation in this model of myocarditis. Neutralization of IFN-gamma significantly increased the severity of myocarditis compared with rat immunoglobulin G and saline controls (p less than 0.0065), suggesting that IFN-gamma may function as an important regulatory cytokine early in the pathogenesis of myocardial inflammation. Understanding the functions of cytokines during the inflammatory response to myocardial injury may provide important information on possible methods to limit myocardial damage.
Tuning the oviduct to the anandamide tone
Authors: H. Schuel
Journal: Journal of Clinical Investigation (2006)

Anandamide (N-arachidonoylethanolamide) is a lipid signal molecule that was the first endogenous agonist for cannabinoid receptors to be discovered. Cannabinoid receptor type 1 (CB1) is widely distributed in neurons and nonneuronal cells in brain and peripheral organs including sperm, eggs, and preimplantation embryos. A study by Wang and colleagues in this issue of the JCI demonstrates that a critical balance between anandamide synthesis by N-acylphosphatidylethanolamine–selective phospholipase D (NAPE-PLD) and its degradation by fatty acid amide hydrolase (FAAH) in mouse embryos and oviducts creates locally an appropriate "anandamide tone" required for normal embryo development, oviductal transport, implantation, and pregnancy (see the related article beginning on page 2122). Adverse effects of elevated levels of anandamide on these processes resulting from FAAH inactivation are mimicked by administration of (-)-Δ9-tetrahydrocannabinol (THC; the major psychoactive constituent of marijuana), due to enhanced signaling via CB1. These findings show that exogenous THC can swamp endogenous anandamide signaling systems, thereby affecting multiple physiological processes.
Physician Complicity in Misrepresentation and Omission of Evidence of Torture in Postdetention Medical Examinations in Turkey
Authors: V Iacopino, M Heisler, S Pishevar, R H Kirschner
Journal: JAMA (1996)

Between June 1994 and October 1995, representatives of Physicians for Human Rights studied the problem of physician complicity in torture (ie, misrepresentation and omission of medical evidence in postdetention examinations of detainees) in Turkey. The research consisted of a survey of forensic documentation of torture, interviews with individual physicians who examine detainees, analyses of official medical reports of detainees, and interviews with survivors of torture. Results from the survey, interviews, and medical report analyses provide evidence that torture of political and criminal detainees continues to occur in Turkey and that Turkish physicians are coerced to ignore, misrepresent, and omit evidence of torture in their examinations of detainees to certify that there are no physical signs of torture.
Pregnancy and the Kidney
Authors: Sharon E Maynard, Ravi Thadhani
Journal: Journal of the American Society of Nephrology (2009)

Nephrologists are frequently called on to diagnose and treat renal disorders in pregnant women. In this review, we update recent literature pertinent to pregnancy and renal disease. We initially begin by describing the application of common clinical estimators of GFR and proteinuria in pregnancy and then summarize recent studies regarding pregnancy in women with chronic kidney disease and the latest information on the use of common renal medications in pregnancy. In the final section, we describe advances in our understanding of the pathophysiology of preeclampsia and the potential clinical implications of these discoveries for screening, prevention, and treatment of preeclampsia.
End of life fears in COPD: The influence of biomedical variables, mental health status and disease specific anxieties
Authors: Isabelle Vaske, Nikola Stenzel, Winfried Rief, Kerstin Kuehl, Klaus Kenn
Journal: European Respiratory Journal (2012)

Introduction  More than half of the COPD-patients report end of life fears. The available research, however, has not yet identified the influence of unspecific and disease specific symptoms on these fears in COPD.  Aims  This study aims at investigating the influence of biomedical variables, mental health status and disease specific anxieties (i.e. dyspnea related fear) on end of life fears (fear of dying, fear of death).  Methods  132 rehabilitation patients with COPD (GOLD-II n=30, GOLD-III n=18, GOLD-IV n=84) completed questionnaires assessing mental health status (Hospital Anxiety and Depression Scale, HADS), disease specific anxieties (COPD anxiety questionnaire, CAF) and end of life fears (Multidimensional Orientation toward Dying and Death Inventory, MODDI-F). Pulmonary function (FEV1 38.83±15.53% pred.), blood-gas analysis and 6-minute walk test (6MWT; 287.39±119.22m) served as biomedical variables.  Results  Hierarchical regression analyses revealed that biomedical variables were not predictive of “fear of dying” (p=.48) and “fear of death” (p=.44). However, mental health status explained incremental variance (“fear of dying”: s=.39; p  Conclusions  Psychotherapeutic interventions for COPD patients might not only consider mental health status, but also disease specific anxieties and end of life fears.
Reduced apoptosis of memory T-cells in the inner airway wall of mild and severe asthma
Authors: J. P. Lamb, A. James, N. Carroll, L. Siena, J. Elliot, A. M. Vignola†
Journal: European Respiratory Journal (2005)

Effector memory T-cells (CD45RO+) may provide pro-inflammatory signals that contribute to the persistent airway inflammation that is characteristic of asthma, and reduced apoptosis of these cells may prolong their effects. The present authors compared apoptosis of CD45RO+ T-cells in the inner airway wall in nonfatal asthma (n = 7), fatal asthma (n = 7) and control (n = 8) cases. Apoptotic cells were identified using both the terminal deoxynucleotidyl transferase dNTP nick end-labelling (TUNEL) technique and cell morphology. The percentage of CD45RO+ T-cells that were apoptotic was significantly greater in control cases compared with nonfatal and fatal cases of asthma, respectively, in small (42±19, 16±9, 7±6%), medium (40±12, 15±11, 12±8%) and large airways (42±15, 23±18, 18±12%). The reduction in the percentage of apoptotic CD45RO+ cells in the cases of asthma was observed in both blood vessels and the interstitium in large airways. In conclusion, these data suggest that reduced apoptosis may prolong the active life of effector memory T-cells in the airways. It is possible that survival signals may be received before cells migrate into the interstitium of the inner airway wall.
Effect of Pexelizumab, an Anti-C5 Complement Antibody, as Adjunctive Therapy to Fibrinolysis in Acute Myocardial Infarction
Authors: Kenneth W. Mahaffey, Christopher B. Granger, Jose C. Nicolau, Witold Ruzyllo, W. Douglas Weaver, Pierre Theroux, Judith S. Hochman, Thomas G. Filloon, Christopher F. Mojcik, Thomas G. Todaro, Paul W. Armstrong
Journal: Circulation (2003)

Background— Complement activation mediates myocardial damage that occurs during ischemia and reperfusion through multiple pathways. We performed 2 separate, parallel, double-blind, placebo-controlled trials to determine the effects of pexelizumab (a novel C5 complement monoclonal antibody fragment) on infarct size in patients receiving reperfusion therapy: COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) and COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA). The COMPLY trial is reported here. Methods and Results— Overall, 943 patients with acute ST-segment elevation myocardial infarction (MI) (20% with isolated inferior MI) receiving fibrinolysis were randomly assigned &lt;6 hours after symptom onset to placebo, pexelizumab 2.0-mg/kg bolus, or pexelizumab 2.0-mg/kg bolus plus 0.05 mg/kg per h for 20 hours. Infarct size determined by creatine kinase–MB area under the curve was the primary analysis, which included patients who received at least some study drug and fibrinolysis (n=920). The median infarct size did not differ by treatment (placebo, 5230; bolus, 4952; bolus plus infusion, 5557 [ng/mL] · h; bolus versus placebo, P =0.85; bolus plus infusion versus placebo, P =0.81), nor did the 90-day composite incidence of death, new or worsening congestive heart failure, shock, or stroke (placebo, 18.6%; bolus, 18.4%; bolus plus infusion, 19.7%). Pexelizumab inhibited complement for 4 hours with bolus-only dosing and for 20 to 24 hours with bolus-plus-infusion dosing, with no increase in infections. Conclusions— When used adjunctively with fibrinolysis, pexelizumab blocked complement activity but reduced neither infarct size by creatine kinase–MB assessment nor adverse clinical outcomes.
Boulevard of Broken Dreams: Drug Approval for Older Adults With Acute Myeloid Leukemia
Authors: Mikkael A. Sekeres, David P. Steensma
Journal: Journal of Clinical Oncology (2012)

weeks) plus supportive care or supportive care alone; almost all patients randomly assigned to the control arm (88%) received LDAC. The primary end point was overall survival. With 485 patients enrolled, the hazard ratio for death for decitabine therapy compared with that for control therapy at the time of the preplanned end point was nonsignificant (0.85; 95% CI, 0.69 to 1.04; P .11), although the complete remission rate in the decitabine arm was more than double that in the control arm (16% v 7%), and the observed median overall survival time was numerically higher in the decitabine arm (7.7 v 5.0 months). Why did decitabine join the ranks of tipifarnib (Zarnestra; Johnson & Johnson, New Brunswick, NJ), clofarabine (Clolar; Genzyme, Cambridge, MA), and laromustine (Onrigin; Vion Pharmaceuticals, New Haven, CT) in failing to convince an FDA panel of its favorable efficacy and safety profile in a population of older and frailer patients with AML who so clearly need additional therapies? There were, of course, factors specific to the negative decision for each of these drugs.
The challenge of managing tendinopathy in competing athletes
Authors: J L Cook, C R Purdam
Journal: British Journal of Sports Medicine (2013)

Managing tendinopathy in season is a challenge for all sports medicine practitioners. Many of the strategies employed to treat tendinopathy in a rehabilitation setting are not suitable because of the time taken to recover. Management strategies that control pain and maintain performance are required. These include load management, both reducing aggravating loads and introducing pain-relieving loads, medications and adequate monitoring to detect a deteriorating tendon. Other interventions such as intratendinous injection therapies and other direct tendon modalities can be provocative at worst and without effect at best. Research to improve the understanding of management in athletes in season is compromised by ethical considerations and access to willing participants. It is likely to remain an area where clinical advances guide future treatments.
A CD56-negative case of blastic natural killer-cell lymphoma (agranular CD4+/CD56+ haematodermic neoplasm)
Authors: T. Petrella, M.A. Teitell, C. Spiekermann, C.J.L.M. Meijer, F. Franck, I. Enache
Journal: British Journal of Dermatology (2004)

Journal Article A CD56‐negative case of blastic natural killer‐cell lymphoma (agranular CD4+/CD56+ haematodermic neoplasm) Get access T. Petrella, T. Petrella Centre de Pathologie, 33 Rue Nicolas Bornier, BP 189, and Laboratoire d'Anatomie Pathologique (Centre Hospitalo‐Universitaire), Dijon 21000, France, Departments of Pathology and Pediatrics, Center for Cell Mimetic Studies (CMISE), Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095‐1732, U.S.A Search for other works by this author on: Oxford Academic Google Scholar M.A. Teitell, M.A. Teitell Centre de Pathologie, 33 Rue Nicolas Bornier, BP 189, and Laboratoire d'Anatomie Pathologique (Centre Hospitalo‐Universitaire), Dijon 21000, France, Departments of Pathology and Pediatrics, Center for Cell Mimetic Studies (CMISE), Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095‐1732, U.S.A Search for other works by this author on: Oxford Academic Google Scholar C. Spiekermann, C. Spiekermann Pathology Search for other works by this author on: Oxford Academic Google Scholar C.J.L.M. Meijer, C.J.L.M. Meijer Department of Pathology, Vrije Universiteit Medical Centre, Amsterdam 1007MB, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar F. Franck, F. Franck Department of Pathology, Hotel Dieu, Clermont‐Ferrand 63000, France E‐mail: tony.petrella@centre‐de‐pathologie.fr Search for other works by this author on: Oxford Academic Google Scholar I. Enache I. Enache Internal Medicine, Centre Hospitalier Régional, Nevers 58000, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 150, Issue 1, 1 January 2004, Pages 174–176, https://doi.org/10.1111/j.1365-2133.2004.05713.x Published: 01 January 2004
[29] VACCINATION WITH DENDRITIC CELLS TRANSDUCED WITH A CD40L-EXPRESSING ADENOVIRUS AND AN AFP-ENCODING ADENOVIRUS INDUCES INHIBITION OF SUBCUTANEOUS HEPATOCELLULAR TUMOR GROWTH IN MICE
Authors: M.A. Gonzalez-Carmona, C. Schneider, I.G. Schmidt-Wolf, V. Schmitz, T. Sauerbruch, W.H. Caselmann
Journal: Journal of Hepatology (2007)
Plasma tumor necrosis factor levels in patients with presumed sepsis. Results in those treated with antilipid A antibody vs placebo
Authors: M A de Groote, M A Martin, P Densen, M A Pfaller, R P Wenzel
Journal: JAMA (1989)

Using an enzyme-linked immunosorbent assay, we measured plasma levels of tumor necrosis factor (TNF) in 38 patients who were treated with either antilipid A antibody or a placebo for presumed gram-negative bacteremia. Sixteen of the 38 patients had positive blood cultures: 14 with gram-negative rods and 2 with Streptococcus pneumoniae. Initial serum samples for TNF determinations were obtained within 2 to 72 hours (mean, 18.8 hours) after the onset of clinical signs of sepsis. Six (16%) of 38 patients had detectable TNF levels: 4 of 14 with positive blood cultures for gram-negative rods but only 2 of 22 with negative blood cultures (odds ratio, 4; 95% confidence limits, 0.5 and 24.3). Of the 6 patients, 4 had received the placebo and 2 had received the antibody. Tumor necrosis factor levels did not predict adult respiratory distress syndrome, shock, disseminated intravascular coagulation, renal failure, or mortality. The highest TNF levels (500 and 250 pg/mL) were observed in 2 patients with Enterobacter cloacae bacteremia who had received the placebo and antilipid A antibody, respectively. The other 2 patients with bacteremia and detectable TNF levels had positive blood cultures for Haemophilus influenzae (50 pg/mL) and Bacteroides fragilis (120 pg/mL), respectively. Despite negative blood cultures, the remaining 2 patients repeatedly had detectable TNF levels and a clinical picture consistent with gram-negative sepsis.