tbuckley/cabot-search huggingface dataset:
Abstract A38: Resistance to Afatinib and Cetuximab Combination Therapy in EGFR-mutant Lung Adenocarcinomas
Authors: Valentina Pirazzoli, Ken Takezawa, Elisa de Stanchina, William Pao, Katerina Politi
Journal: Clinical Cancer Research (2012)

Abstract The epidermal growth factor receptor (EGFR) T790M mutation confers acquired resistance to tyrosine kinase inhibitors (TKIs) in approximately 50% of drug-resistant EGFR mutant lung adenocarcinomas. Experiments using genetically engineered mouse models of EGFR mutant lung cancer have revealed that T790M-mediated resistance can be overcome by a second-generation TKI, afatinib, in combination with the anti-EGFR antibody, cetuximab. This drug combination is currently in clinical trials in patients with TKI-resistant tumors and is showing a promising ∼40% response rate. Nevertheless, cases of afatinib+cetuximab resistance are beginning to emerge. To identify the molecular mechanisms that play a role in afatinib+cetuximab resistance and test new therapies to overcome resistance to these drugs, we have developed mouse models of afatinib+cetuximab resistance in mice with inducible expression of the EGFRL858R+T790M mutant in type II pneumocytes. Mice harboring lung tumors were treated five days a week with afatinib and twice a week with cetuximab for four weeks. After the first round of treatment, drug-treatments were interrupted for one month. This on/off drug treatment was repeated until lung tumors no longer responded to treatment, as evidenced by imaging as well as clinical symptoms. Resistance to afatinib+cetuximab treatment was also studied in xenografts. Eight-week-old nu/nu athymic nude mice were injected subcutaneously with human lung adenocarcinoma cells, expressing the erlotinib-resistant EGFRDel19+T790M mutant. Notably, both transgenic and xenografts models harboring EGFRT790M-induced tumors developed resistance to EGFR-dual targeting and preliminary molecular studies on the resistant tumors show the absence of additional mutations in EGFR and in the ERBB2 tyrosine kinase domain in resistant tumors. These findings suggest that an alternative pathway or mechanism is involved in mediating resistance to the afatinib and cetuximab combination. We are further exploring mechanisms of resistance by performing genome-wide and signaling pathway analyses of drug-resistant tumors from these models. Findings from mouse models will be validated in repeat biopsy specimens from patients who have developed resistance to the drug combination. An improved understanding of the molecular mechanisms responsible for acquired resistance to EGFR inhibition will provide new insight into the biology of this subset of lung cancers with immediate therapeutic implications for patients.
84 SAFETY, TOLERABILITY AND PRELIMINARY ACTIVITY OF GS-9450, A SELECTIVE CASPASE INHIBITOR, IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS (NASH)
Authors: V. Ratziu, M. Chojkier, M.Y. Sheikh, A.J. Sanyal, J.K. Lim, H. Conjeevaram, N. Chalasani, M. Abdelmalek, A. Bakken, C. Renou, M. Palmer, R. Levine, R. Bhandari, M. Cornpropst, W. Liang, B. King, E. Mondou, F.S. Rousseau
Journal: Journal of Hepatology (2010)
Neuromuscular Versus Quadriceps Strengthening Exercise in Patients With Medial Knee Osteoarthritis and Varus Malalignment: A Randomized Controlled Trial
Authors: Kim L. Bennell, Mary Kyriakides, Ben Metcalf, Thorlene Egerton, Tim V. Wrigley, Paul W. Hodges, Michael A. Hunt, Ewa M. Roos, Andrew Forbes, Eva Ageberg, Rana S. Hinman
Journal: Arthritis & Rheumatology (2013)

Objective To compare the effects of neuromuscular exercise (NEXA) and quadriceps strengthening (QS) on the knee adduction moment (an indicator of mediolateral distribution of knee load), pain, and physical function in patients with medial knee joint osteoarthritis (OA) and varus malalignment. Methods One hundred patients with medial knee pain, mostly moderate‐to‐severe radiographic medial knee OA, and varus malalignment were randomly allocated to one of two 12‐week exercise programs. Each program involved 14 individually supervised exercise sessions with a physiotherapist plus a home exercise component. Primary outcomes were peak external knee adduction moment (3‐dimensional gait analysis), pain (visual analog scale), and self‐reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index). Results Eighty‐two patients (38 [76%] of 50 in the NEXA group and 44 [88%] of 50 in the QS group) completed the trial. There was no significant between‐group difference in the change in the peak knee adduction moment (mean difference 0.13 Nm/[body weight × height]% [95% confidence interval (95% CI) −0.08, 0.33]), pain (mean difference 2.4 mm [95% CI −6.0, 10.8]), or physical function (mean difference −0.8 units [95% CI −4.0, 2.4]). Neither group showed a change in knee moments following exercise, whereas both groups showed similar significant reductions in pain and improvement in physical function. Conclusion Although comparable improvements in clinical outcomes were observed with both neuromuscular and quadriceps strengthening exercise in patients with moderate varus malalignment and mostly moderate‐to‐severe medial knee OA, these forms of exercise did not affect the knee adduction moment, a key predictor of structural disease progression.
GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier
Authors: Glen Seidner, Marcela Garcia Alvarez, Jih-I Yeh, Kevin R. O'Driscoll, Jörg Klepper, Tammy S. Stump, Dong Wang, Nancy B. Spinner, Morris J. Birnbaum, Darryl C. De Vivo
Journal: Nature Genetics (1998)
Dermoscopic monitoring of melanocytic skin lesions: clinical outcome and patient compliance vary according to follow-up protocols
Authors: G. Argenziano, I. Mordente, G. Ferrara, A. Sgambato, P. Annese, I. Zalaudek
Journal: British Journal of Dermatology (2008)

Dermoscopic monitoring of melanocytic lesions increases the likelihood that featureless melanomas are not overlooked and minimizes the excision of benign lesions. Objective To examine clinical outcome and patient compliance using different follow-up protocols.A retrospective analysis of 600 lesions from 405 patients (aged 6-79 years) was performed to examine patient compliance and clinical outcome in patients with multiple atypical melanocytic lesions undergoing sequential dermoscopy imaging during short-, medium- or long-term follow-up. Based on the degree of dermoscopic atypical features, patients were scheduled for short-term monitoring with follow-up after 3 months, medium-term monitoring with follow-up after 6 months or long-term monitoring with annual follow-up. Criteria leading to excision of monitored lesions differed according to the follow-up protocol.In a median follow-up period of 23 months, 54 (9%) lesions were excised, revealing 12 early melanomas (occurring in 3% of monitored patients), one basal cell carcinoma and 41 melanocytic naevi. The melanoma/benign ratio of excised lesions was 1 : 3.4. Seven of 12 melanomas showed changes after two to four visits, corresponding to 8-54 months of follow-up. Patient compliance was 84% for short-term monitoring, 63% for medium-term monitoring and 30% for long-term monitoring.In patients with multiple naevi sequential dermoscopy imaging is a useful strategy to avoid missing melanomas while minimizing unnecessary excision of benign lesions. For better compliance, the first re-examination should be scheduled at 3 months after the baseline visit. Regular annual follow-up monitoring is also needed to detect slow-growing melanomas in which subtle changes may become apparent only over time.
340 PERFORMANCE OF ACOUSTIC RADIATION FORCE IMPULSE IMAGING IN THE NONINVASIVE ASSESSMENT OF LIVER FIBROSIS, IN COMPARISON TO FIB4 SCORE
Authors: M. Lupsor, R. Badea, H. Stefanescu, D. Feier, D. Crisan, C. Radu, A. Serban, Z. Sparchez, A. Maniu
Journal: Journal of Hepatology (2011)
The Anatomy of Bereavement
Authors: Alan Stoudemire
Journal: JAMA (1984)

In a volume that will likely become a classic, Dr Beverley Raphael has written definitively on the topic of bereavement. Her writing reflects not only a superb knowledge of the subject, but also a thoughtfully compassionate manner showing the wisdom of an experienced clinician. One is impressed by the book's comprehensive scope. Dr Raphael uses a developmental model in discussing the forms of bereavement as they are manifested throughout life, from infancy to old age. She invokes not only traditional psychodynamic theories of grief, but draws from learning and behavioral theories as well. The concept of bereavement is not limited to the death of loved ones but is applied to emotional reactions to other types of losses: body parts, health status, and employment. While the literature on grief has often focused on bereavement reactions in adults (particularly widows and widowers), a discussion of grief reactions during each stage of childhood
Functional human regulatory T cells fail to control autoimmune inflammation due to PKB/c-akt hyperactivation in effector cells
Authors: Ellen J. Wehrens, Gerdien Mijnheer, Chantal L. Duurland, Mark Klein, Jenny Meerding, Jorg van Loosdregt, Wilco de Jager, Birgit Sawitzki, Paul J. Coffer, Bas Vastert, Berent J. Prakken, Femke van Wijk
Journal: Blood (2011)
Predictors of one-year pretransplant survival in patients with cirrhosis
Authors: Michael Oellerich, Martin Burdelski, Hans-Ulrich Lautz, Lutz Binder, Rudolf Pichlmayr
Journal: Hepatology (1991)

The aim of this prospective study was to examine the usefulness of flow-dependent dynamic liver function tests and conventional methods of evaluating liver function as predictors of pretransplant survival in patients with advanced cirrhosis. Patients who underwent orthotopic liver transplantation within the follow-up period of 365 days were excluded. One hundred one patients with histologically confirmed cirrhosis were studied. Fifty-eight patients had post-hepatitic cirrhosis, 13 had cryptogenic cirrhosis and 30 had biliary cirrhosis. During follow-up, 28 patients died of their liver diseases. At entry, we recorded indocyanine green half-life, monoethylglycinexylidide formation from lidocaine, bilirubin and albumin serum concentrations, activities of cholinesterase and alkaline phosphatase, prothrombin time, clinical complications of ascites and encephalopathy and the Pugh score. These variables were subjected as covariates to a stepwise survival analysis by use of the Cox proportional-hazards model. At the final step, Pugh score, monoethylglycinexylidide formation and indocyanine green half-life were found to be the only independent variables significantly related to 1-yr survival. The parallel combination of Pugh score and monoethylglycinexylidide test yielded the highest prognostic sensitivity (82%). The series approach combining either the Pugh score and indocyanine green test or the monoethylglycinexylidide and indocyanine green tests was associated with the highest specificity (96%/97%) and high predictive values of a positive result (81%/82%). These findings suggest that appropriate combinations of the studied flow-dependent dynamic liver function tests and the Pugh score could be useful in improving transplant candidate selection and the timing of transplantation.
Collagen metabolism in experimental cardiac hypertrophy in the rat and the effect of digitoxin treatment
Authors: H. TURTO
Journal: Cardiovascular Research (1977)

Journal Article Collagen metabolism in experimental cardiac hypertrophy in the rat and the effect of digitoxin treatment Get access H. TURTO H. TURTO 2 From the Department of Medical Chemistry, University of Helsinki, Finland 2Address for correspondence and reprints: Dr Heikki Turto, Department of Medical Chemistry, University of Helsinki, Siltavuorenpenger 10, 00170 Helsinki 17, Finland. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 11, Issue 4, July 1977, Pages 358–366, https://doi.org/10.1093/cvr/11.4.358 Published: 01 July 1977
Clinical Procedures in Emergency Medicine
Authors: Roy M. Colven
Journal: JAMA (1992)

The editors' premise is that "emergency medicine is a procedure-oriented specialty," and this second edition of Roberts and Hedges'<i>Clinical Procedures in Emergency Medicine</i>could be the specialty's procedural standard of reference. The authors do not offer a cookbook approach, but, rather, editors James Roberts, of the University of Cincinnati, and Jerris Hedges, of the Oregon Health Sciences University, have blended step-by-step instruction with general background, pertinent pathophysiology, clinical rationale, complications, and painstakingly chosen references. This scholarly work makes the volume the complete physician's how-to manual for emergency department procedures and an academic procedural textbook. Physically, it is a sturdy 1166 pages. Photographs, radiographs, and diagrams are well chosen, cleanly reproduced, and, generally, on the same page as the referent text. The tables are not overused but are simple in design and concise, containing important information not readily conveyed in narrative form. The text, however, is what separates and elevates
Nierenkrankheiten: Physiologie, Pathophysiologie, Untersuchungsmethoden Klinik und Therapie
Authors: Kurt Lange
Journal: JAMA (1968)

This third edition, adding much new material, has several collaborators, which explains a certain uneven quality. Following a detailed table of the most important normal values—very helpful for anyone working in nephrology—the book discusses the physiology of the kidney with an excellent concise and clear description of modern ideas on renal physiology. It is probably the most valuable part of the book. Chapters on examinations of the urine and blood and the roentgenologic diagnosis of kidney diseases, on clinic and pathogenesis of the main renal diseases, on electrolyte disturbances and urolithiasis as well as on general kidney and therapeutic techniques follow the physiologic introduction. The clinical part deviates in several respects from the opinions widely accepted in this country. In general, the book does not adequately relate clinical findings and results of kidney biopsies, which the author considers somewhat dangerous and performs only in a few selected cases. Electrophoresis of
Fluconazole for the Treatment of Cutaneous Leishmaniasis Caused by<i>Leishmania major</i>
Authors: Abdulrahman A. Alrajhi, Elfaki A. Ibrahim, Edward B. De Vol, Mohammad Khairat, Rajab M. Faris, James H. Maguire
Journal: New England Journal of Medicine (2002)

Whereas certain oral antifungal azoles are well documented to have activity against leishmania, data on the efficacy of fluconazole for leishmaniasis are limited. We conducted a controlled trial in Saudi Arabia of fluconazole for the treatment of cutaneous leishmaniasis caused by Leishmania major.
Adenine Arabinoside Therapy of Herpes Zoster in the Immunosuppressed
Authors: Richard J. Whitley, Lawrence T. Ch'ien, Raphael Dolin, George J. Galasso, Charles A. Alford
Journal: New England Journal of Medicine (1976)

We evaluated adenine arabinoside treatment of herpes zoster in immunodeficient patients in a randomized, controlled crossover study. The two study groups had similar characteristics. In spite of rapid natural healing, those receiving adenine arabinoside over the first five days had accelerated clearance of virus from vesicles (P = 0.01), and cessation of new vesicle formation (P = 0.004), and a shorter time to total pustulation (P = 0.001). Factors modifying the response to therapy included age, underlying disease, and the duration of zoster prior to therapy. Clinical toxicity was minimal. Laboratory assessment of bone-marrow, liver and renal function showed insignificant alterations as a result of therapy. These studies show that adenine arabinoside is a drug with promise for therapy of systemic herpes zoster in immunocompromised patients. It is most efficacious when administered during the first six days of disease (P = 0.001) to those who have reticuloendothelial neoplasia (P = 0.001) and are less than 38 years of age (P = 0.001).
Männer Zwischen 15 und 25 Jahren. Mentalhygienische Untersuchungen mit besonderer Berücksichtigung der Schizophrenie. By<i>Trygve Braatøy.</i>(Oslo: Druck und Verlag von Fabritius &amp; Sønner 1934.)
Authors: J. Notkin
Journal: American Journal of Psychiatry (1936)
Reply to J.A. Ajani et al
Authors: Thomas Ruhstaller, Viviane Hess
Journal: Journal of Clinical Oncology (2011)

We are quite underwhelmed by the level of enthusiasm expressed by the authors in the article by the Swiss Group for Clinical Cancer Research (SAKK). 1 A pathologic complete response (pathCR) usually does not exceed 25% when the number of patients analyzed is much larger [2][3][4] than in this article.When the sample size is small, no meaningful conclusions can be drawn about the pathCR rates or other categories of response.In this article, pathologic response data were available for only 28 patients (15 patients with adenocarcinoma), and pathCR occurred in only 32% of patients (no CIs are provided, but they are wide).We would sound a note of caution in interpreting these results, and we are concerned about the announcement of a phase III investigation that is based on these results.Although investigation of a biologic agent in an empiric fashion remains the contemporary approach, some efforts should be made to identify various patient subsets on the basis of tumor biology.If the authors do not have an infrastructure to support these types of investigations, then at least a phase II randomized trial should be proposed to find a strong signal before committing valuable patient resources to a lengthy, large investigation.We believe that three categories of response (complete, partial, and none) need to be specifically characterized because one can conceive the development of therapeutic strategies to each category of response.For example, if one could identify those patients who are destined to achieve a pathCR with a reasonably high rate of sensitivity and a particularly high rate of specificity, the esophagus could be preserved and surgery could be used as a salvage therapy.Similarly, patients who have some response to chemoradiotherapy will most likely benefit from trimodality therapy; however, patients with ex-tremely chemoradiotherapy-resistant tumors should not undergo chemoradiotherapy and can go straight into surgery while we sort out the ways to overcome chemoradiotherapy resistance.We recognize that these algorithms are not available for execution now and that their development remains a challenge, but combining these response categories (as the authors have done 1 ) does not convey any additional information or importance but simply generates euphoria.We could make many other points about this article, but we believe that the authors should reconsider their developmental plans for cetuximab in this setting.
Perianal Langerhans cell histiocytosis relieved by surgical excision
Authors: T. Mittal, M.D.P. Davis, R.B. Lundell
Journal: British Journal of Dermatology (2008)

Journal Article Perianal Langerhans cell histiocytosis relieved by surgical excision Get access T. Mittal, T. Mittal Department of Dermatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, U.S.A. E‐mail: mittal.t@mayo.edu Search for other works by this author on: Oxford Academic Google Scholar M.D.P. Davis, M.D.P. Davis Department of Dermatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, U.S.A. E‐mail: mittal.t@mayo.edu Search for other works by this author on: Oxford Academic Google Scholar R.B. Lundell R.B. Lundell Department of Dermatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, U.S.A. E‐mail: mittal.t@mayo.edu Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 160, Issue 1, 1 January 2009, Pages 213–215, https://doi.org/10.1111/j.1365-2133.2008.08934.x Published: 01 January 2009
Hazard of Platelet Transfusion in Thrombotic Thrombocytopenic Purpura
Authors: Donald R. Harkness
Journal: JAMA (1981)

A patient with thrombotic thrombocytopenic purpura (TTP) showed for the first time catastrophic signs and symptoms of CNS involvement immediately after infusion of platelets. Postmortem examination revealed extensive deposits of platelet aggregates within the small blood vessels of the brain, whereas lesions elsewhere in the body consisted of platelets as well as fibrin and were associated with endothelial proliferation and microaneurysm formation. These findings are consistent with the view that the initial event in TTP may be platelet aggregation. The plasma of this patient contained platelet-aggregating activity. We conclude that platelet transfusions in patients with TTP may aggravate the disease process.
Coronary Computed Tomography Angiography as a Screening Tool for the Detection of Occult Coronary Artery Disease in Asymptomatic Individuals
Authors: Eue-Keun Choi, Sang Il Choi, Juan J. Rivera, Khurram Nasir, Sung-A. Chang, Eun Ju Chun, Hyung-Kwan Kim, Dong-Joo Choi, Roger S. Blumenthal, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2008)
Outcomes of Older Patients Receiving Chronic Dialysis
Authors: Donna J. Brogan
Journal: JAMA (1994)

<h3>To the Editor.</h3> —Ms Byrne and colleagues<sup>1</sup>present 1-, 3-, and 5-year survival rates for patients in the United States beginning dialysis at 55 years of age or older, by age and cause of ESRD (primary diagnosis) at initiation of dialysis. They state that their data "should prove useful to those... making clinical decisions about the appropriateness of initiating chronic dialysis in older patients." The authors imply that dialysis might not be offered to patients in particular age groups and primary diagnosis groups, such as older patients with diabetes as the cause of ESRD. They acknowledge that additional factors are likely related to survival, eg, comorbidities, nutritional status, compliance with treatment, and adequacy of dialysis, but they do recommend that analyses based on age and primary diagnosis may be used to make decisions regarding rationing of dialysis. Following the authors' recommendations would differentially affect rationing dialysis for older blacks,
Race and Sex Differences in Metabolic Control of Adolescents With IDDM: A Function of Psychosocial Variables?
Authors: Cindy L Hanson, Scott W Henggeler, George A Burghen
Journal: Diabetes Care (1987)

Race and sex differences have been reported in the prevalence of complications from insulin-dependent diabetes mellitus (IDDM). Because metabolic control is assumed to be associated with the probability of developing future complications, race and sex differences in metabolic control were assessed in a group of adolescents. Subjects were 27 Black and 27 White adolescents who were similar in age, age at diagnosis, and social class. Girls did not differ on number of days since their last menses. A 2-by-2 (race-by-sex) analysis of variance revealed that the Black female group had worse HbAlc than each of the other groups (P &amp;lt; .012). Multivariate analyses of variance were conducted to determine whether the poor metabolic control of the Black girls was associated with pertinent psychosocial variables. The analyses revealed that their poor control was not associated with a deficiency in the girls' knowledge about IDDM, adherence to treatment, self-concept, coping patterns, family functioning, stress, social support, or involvement in the health-care system. If the poor control of the Black girls is not associated with psychosocial deficiencies, biological variables or psychosocial variables not assessed in this study are probably operative.
Putative B-cell Apoptosis as a Cause of Hypogammaglobulinemia in Carbamazepine Hypersensitivity: A Case Report
Authors: J.A. Bird, D.M. Anmuth, E. Muscal, M.K. Dishop, C.L. Nance, S.L. Abramson
Journal: Journal of Allergy and Clinical Immunology (2007)