tbuckley/cabot-search huggingface dataset:
Treatment of<i>EGFR</i>-Mutant Lung Cancers After Progression in Patients Receiving First-Line EGFR Tyrosine Kinase Inhibitors
Authors: Zofia Piotrowska, Lecia V. Sequist
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Patients with<i>EGFR</i>-mutant lung cancer benefit from treatment with EGFR inhibitors such as erlotinib, gefitinib, and afatinib, but outcomes are limited by the eventual development of resistance to these agents. Over half of patients acquire a secondary T790M mutation in<i>EGFR</i>at the time of progression and a substantial minority develops resistance through other mechanisms. Multiple treatment strategies are now available to patients whose disease has progressed on their initial EGFR inhibitor, including therapies targeting both T790M, and non–T790M-mediated resistance. <h3>Observations</h3> This review summarizes information about and current treatment strategies for patients with<i>EGFR</i>-mutant lung cancer whose disease progresses on their initial EGFR inhibitor, including those with T790M and other types of acquired resistance. Postprogression therapy should be tailored based on identified resistance mechanisms, sites, and pace of disease progression, and patient preference. Biopsy and genotyping of resistant tissue or plasma are essential to identifying resistance mechanisms and selecting the most appropriate treatment when patients' disease progresses during treatment with an initial EGFR inhibitor. Third-generation EGFR inhibitors are generally preferred for patients with T790M-positive resistance, whereas standard chemotherapy and clinical trials are preferred for those without T790M. For select patients, treatment can be continued beyond progression and local ablative therapies can be used to target sites of oligoprogression. <h3>Conclusions and Relevance</h3> Treatment for patients who progress on their initial EGFR inhibitor should be tailored to identified resistance mechanisms and sites of progression. Emerging reports about resistance to third-generation EGFR inhibitors will lay the groundwork for overcoming the next generation of resistance, and further research is needed to develop more effective therapies.
Biologic Testing of 3,4,9,10-Dibenzpyrene&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: Susheela S. Waravdekar, Kamal J. Ranadive
Journal: JNCI Journal of the National Cancer Institute (1958)

A reduction product of a vat dye, 3,4,9,10-dibenzpyrene, was tested for its carcinogenic activity. The potent activity of this compound, when administered subcutaneously, was shown by the high carcinogenic index and low latent period. The carcinogenic activity of 3,4,9,10-dibenzpyrene and two related polycyclic hydrocarbons was discussed in relation to the K-region hypothesis.
A nonsense mutation in the DNA repair factor Hebo causes mild bone marrow failure and microcephaly
Authors: Shu Zhang, Corinne Pondarre, Gaelle Pennarun, Helene Labussiere-Wallet, Gabriella Vera, Benoit France, Marie Chansel, Isabelle Rouvet, Patrick Revy, Bernard Lopez, Jean Soulier, Pascale Bertrand, Isabelle Callebaut, Jean-Pierre de Villartay
Journal: The Journal of Experimental Medicine (2016)

Inherited bone marrow failure syndromes are human conditions in which one or several cell lineages of the hemopoietic system are affected. They are present at birth or may develop progressively. They are sometimes accompanied by other developmental anomalies. Three main molecular causes have been recognized to result in bone marrow failure syndromes: (1) defects in the Fanconi anemia (FA)/BRCA DNA repair pathway, (2) defects in telomere maintenance, and (3) abnormal ribosome biogenesis. We analyzed a patient with mild bone marrow failure and microcephaly who did not present with the typical FA phenotype. Cells from this patient showed increased sensitivity to ionizing radiations and phleomycin, attesting to a probable DNA double strand break (dsb) repair defect. Linkage analysis and whole exome sequencing revealed a homozygous nonsense mutation in the ERCC6L2 gene. We identified a new ERCC6L2 alternative transcript encoding the DNA repair factor Hebo, which is critical for complementation of the patient’s DNAdsb repair defect. Sequence analysis revealed three structured regions within Hebo: a TUDOR domain, an adenosine triphosphatase domain, and a new domain, HEBO, specifically present in Hebo direct orthologues. Hebo is ubiquitously expressed, localized in the nucleus, and rapidly recruited to DNAdsb’s in an NBS1-dependent manner.
C-BOP-3BEP as induction chemotherapy (CT) in nonseminomatous germ cell tumor (NSGCT) patients with poor prognosis
Authors: A. Tryakin, S. Tjulandin, D. Titov, T. Zakharova, K. Figurin, I. Feinstein, A. Garin
Journal: Journal of Clinical Oncology (2004)

4748 Background: Based on the results of Horwich A. et al. (Proc Am Soc Clin Oncol 1997, No 1137) a phase II study the efficacy and toxicity C-BOP-3BEP regimen in the treatment of NSGCT pts with poor prognosis had been performed. Methods: CT-naïve NSGCT pts with poor prognosis (IGCCCG) have received C-BOP as follows: weeks 1 and 3: cisplatin (P) 20 mg/m2 days 1–5, vincristine (O) 2 mg day 1, bleomycin (B) 15 mg day 1; weeks 2 and 4: P 40 mg/m2 and carboplatin AUCx3 day 1, B 15 mg/day as continuous i.v. infusion days 1–5 and O 2 mg day 1; weeks 5 and 6: O 2 mg and B 15 mg day 1. On week 7, 10 and 13 of BEP regimen (P 20 mg/m2 and etoposide 100 mg/m2 days 1–5, B 15 mg days 1,3,5) was delivered. Results: From September, 1997 to May, 2002 35 pts were treated. Pts characteristics: median age 24 (range 15 –43) years; primary site: testis - 21, retroperitoneal - 1, mediastinal (MP) - 13 pts. Median follow-up for cured pts is 31 months (range, 6 – 52). CR after CT and after CT plus surgery was achieved in 2 (6%) and 8 (23%) pts, respectively. 11 (31%) pts with partial response normalized their marker levels and 14 (40%) pts were classified as treatment failure (progression disease or incomplete resection of viable tumor). There were 2 toxic deaths due to acute renal insufficiency and bleomycin-related pulmonitis. Grade 3–4 neutropenia (56%) and thrombocytopenia (44%) were major toxicities. For all pts 3-years PFS and OS were 44% and 53%, and for MP pts – 50% and 64%, respectively, which are very similar to results of BEP/VIP induction CT in our historical control. Conclusions: our experience suggests that C-BOP-3BEP regimen unlikely improve treatment outcomes in NSGCT pts with poor prognosis. No significant financial relationships to disclose.
Whipple's Disease
Authors: Florence Fenollar, Xavier Puéchal, Didier Raoult
Journal: New England Journal of Medicine (2007)

In 2000, Tropheryma whipplei was finally identified as the cause of Whipple's disease, a chronic condition with protean manifestations that was first described in 1907. This review discusses the epidemiology, pathogenesis, diagnosis, and treatment of this rare and elusive chronic disease.
Frequency and presentation of depressive symptoms in patients with primary degenerative dementia [published erratum appears in Am J Psychiatry 1987 Apr;144(4):542]
Authors: L W Lazarus, N Newton, B Cohler, J Lesser, C Schweon
Journal: American Journal of Psychiatry (1987)

The authors examined the frequency and severity of depressive symptoms in elderly patients with presumed primary degenerative dementia and identified the signs and symptoms that provide a reliable basis for diagnosing depression. Forty-four patients and 42 control subjects were interviewed and rated on the Hamilton Rating Scale for Depression and the Sandoz Clinical Assessment-Geriatric Scale. Nine of the patients demonstrated symptoms suggestive of mild, four of moderate, and five of severe depression. Patients had significantly higher scores than control subjects on items that assess intrapsychic rather than vegetative symptoms of depression. These findings underline the importance of maintaining a high index of suspicion for concomitant depressive symptoms in patients with primary degenerative dementia.
Second-line chemotherapy in patients with biliary tract cancer.
Authors: G. Brandi, S. Di Girolamo, F. de Rosa, J. Corbelli, V. Agostini, I. Garajova, C. Longobardi, M. Paragona, G. Ercolani, A. D. Pinna, G. Biasco
Journal: Journal of Clinical Oncology (2011)

e14590 Background: Biliary tract cancers are rare malignancies with a very poor prognosis. Several studies comparing chemotherapy and supportive care showed significant survival prolongation and improvement in life quality with chemotherapy. The association of gemcitabine and a platinum compound is considered the standard first-line treatment but there are no adequate data supporting any second-line therapy. Our retrospective study aims at evaluating retrospectively the impact of second-line chemotherapy in this setting. Methods: We reviewed medical records of patients (pts) affected by histologically confirmed biliary tract cancer, treated in our institution from 2005 to 2010 with a second line chemotherapy after first-line treatment progression. Results: We identified 121 pts progressing after first-line chemotherapy. 56 (46%) of these were considered fit for a second-line treatment and 49 (40%) were effectively treated. Of these 49, 34 had relapsed after radical surgery and 15 were unresectable at diagnosis. The primary site was intrahepatic in 25 pts, extrahepatic in 18 and gallbladder in 6. The first-line schedules were mainly gemcitabine plus a platinum compound (n=35) or gemcitabine plus capecitabine (n=8). As second line, gemcitabine plus a platinum compound and gemcitabine plus capecitabine were delivered respectively in 15 and 14 pts. The remaining 20 were treated with other regimens (6 gemcitabine plus irinotecan, 14 monochemotherapy). Median time to progression was 3.5 months (IC95% 2.0-5.0) and median overall survival, calculated since second-line treatment start, was 8.1 months (IC95% 4.3-11.9). Median overall survival calculated since first-line start was 18.7 months (IC95% 13.9-23.5). Conclusions: Many patients affected by biliary tract cancer have still a good performance status after first-line chemotherapy and could be treated in second-line with potential survival benefit. The optimal regimen has not yet been identified.
Ethics in the practice of psychiatry--origins, functions, models, and enforcement
Authors: R A Moore
Journal: American Journal of Psychiatry (1978)

The author points out that psychiatric ethics are coming under increasing critical scrutiny by psychiatrists and by those outside of the profession. On the basis of an examination of APA Ethics Committee records, he concludes that criticism of psychiatry's inability to police itself might have some merit but cautions that the critics might be expecting too much from a code of ethics, which has the job of sensitizing psychiatrists to an ethical way of professional life and helping sort out ethical conflicts. After outlining a number of the problems in the self-policing aspect of ethics, the author makes suggestions for their resolution.
Likelihood of ACL graft rupture: not meeting six clinical discharge criteria before return to sport is associated with a four times greater risk of rupture
Authors: Polyvios Kyritsis, Roald Bahr, Philippe Landreau, Riadh Miladi, Erik Witvrouw
Journal: British Journal of Sports Medicine (2016)

<h3>Background</h3> The decision as to whether or not an athlete is ready to return to sport (RTS) after ACL reconstruction is difficult as the commonly used RTS criteria have not been validated. <h3>Purpose</h3> To evaluate whether a set of objective discharge criteria, including muscle strength and functional tests, are associated with risk of ACL graft rupture after RTS. <h3>Materials and methods</h3> 158 male professional athletes who underwent an ACL reconstruction and returned to their previous professional level of sport were included. Before players returned to sport they underwent a battery of discharge tests (isokinetic strength testing at 60°, 180° and 300°/s, a running t test, single hop, triple hop and triple crossover hop tests). Athletes were monitored for ACL re-ruptures once they returned to sport (median follow-up 646 days, range 1–2060). <h3>Results</h3> Of the 158 athletes, 26 (16.5%) sustained an ACL graft rupture an average of 105 days after RTS. Two factors were associated with increased risk of ACL graft rupture: (1) not meeting all six of the discharge criteria before returning to team training (HR 4.1, 95% CI 1.9 to 9.2, p≤0.001); and (2) decreased hamstring to quadriceps ratio of the involved leg at 60°/s (HR 10.6 per 10% difference, 95% CI 10.2 to 11, p=0.005). <h3>Conclusions</h3> Athletes who did not meet the discharge criteria before returning to professional sport had a four times greater risk of sustaining an ACL graft rupture compared with those who met all six RTS criteria. In addition, hamstring to quadriceps strength ratio deficits were associated with an increased risk of an ACL graft rupture.
Stenting for Renal-Artery Stenosis
Authors: Luca Zanoli, Carmelita Marcantoni, Pietro Castellino
Journal: New England Journal of Medicine (2014)

Nikolaidou et al. suggest that patients with moderate-to-severe hypertension who receive 3 or more antihypertensive medications may benefit from renal-artery stenting.Patients in the CORAL study received 3.3 to 3.5 antihypertensive medications, yet the clinical outcomes were not improved by stenting.As we reported, there was also not a significant interaction effect for systolic blood pressure of 160 mm Hg or higher on the rate of clinical events according to treatment group.Tomoda suggests that specific subgroups of patients, including those with severe stenosis or heart failure, may benefit from stenting.In our study, we found no benefit in patients with severe stenoses (≥80% according to investigator evaluation) or with global ischemia, and we found no benefit in preventing hospital admissions for heart failure.Approximately 12 to 15% of the patients had heart failure at study entry.Some people, such as those with severe kidney disease or rapidly progressive renal failure, may not have been well represented in the study.Renal-artery stenting may benefit some of the patients described by Tomoda; however, data are lacking from randomized, controlled clinical trials to support that hypothesis.The results of our study suggest that most patients in stable condition should receive medical therapy regardless of the initial level of kidney function.In reply to Leesar and colleagues: a type II error is possible, but the CORAL study was designed to achieve and did achieve adequate power to exclude a meaningful benefit with respect to the prevention of clinical events.Leesar et al. ask whether patients with a pressure gradient across the renal-artery stenosis might benefit from renal-artery stenting, as is suggested in several studies that used a surrogate end point, systolic blood pressure, as the outcome.In our study, we found a small but significant reduction in systolic blood pressure of 2 mm Hg favoring stent treatment; this reduction did not translate into a benefit with respect to event-free survival.In our study, we did obtain data on trans-lesional renal-artery pressure gradients, and analyses of these data should be informative about the value of determinations of pressure gradients.
Carcinoma of the Male Breast: Experience at Hartford Hospital 1930-1960
Authors: G V SMITH, R W PAINTER
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Sensitivity of Proliferating Cultured Murine Pancreatic Tumor Cells to Selected Antitumor Agents&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: L J Wilkoff, E A Dulmadge
Journal: JNCI Journal of the National Cancer Institute (1986)

Cultured cell populations derived from the refractory murine pancreatic ductal adenocarcinoma (Panc 02) were propagated in modified Eagle's minimal essential medium supplemented with 20% fetal bovine serum and had a doubling time of 19.1 +/- 4.7 hours (mean +/- SD). The Panc 02 cell populations were tested against 8 antitumor agents and exhibited different sensitivities to the agents in a 24-hour growth-inhibition assay. The concentration that inhibits the growth of the test culture by 50% relative to the growth of the control culture (IC50) in micromolars was determined for each agent. The IC50 values were: doxorubicin (ADR), 0.055; vincristine (VCR), 0.042; 5-fluorouracil, 1.92; cytarabine, 5.35; melphalan, 10.5; cisplatin, 17.0; carmustine (BCNU), 46.2; and lomustine (CCNU), 52.6. These IC50's were estimated to be pharmacologically attainable concentrations in mice. On a micromolar basis, the Panc 02 cells were the most sensitive to VCR and ADR and the least sensitive to BCNU and CCNU. By the use of a colony-forming assay and a 24-hour exposure period and the evaluation of each agent at 1/3 X IC50, 1 X IC50, and 3 X IC50, the degree of cell killing was greater than predicted on the basis of the IC50's determined in the growth-inhibition assay. The use of a 1-hour exposure period resulted in a very minimal reduction in viability of the cell populations except for BCNU and CCNU. It was concluded that the degree of cell killing was a function of drug concentration and time of exposure and that the pancreatic tumor in vivo should be sensitive to these agents, provided effective concentrations and exposure periods can be achieved at the tumor target sites.
Hamster Ependymomas Produced by Intracerebral Inoculation of a Human Papovavirus (MMV)
Authors: J. Costa, C. Yee, T. S. Tralka, A. S. Rabson
Journal: JNCI Journal of the National Cancer Institute (1976)

Ependymomas were produced in 3 of 11 newborn hamsters inoculated intracerebrally with a human papovavirus (MMV) isolated from a malignant lymphoma of the brain of a child with Wiskott-Aldrich syndrome. One of the tumors was serially transplanted into weanling hamsters. Cells from the transplanted tumors and from cell cultures derived from these tumors contained an intranuclear "T" antigen that reacted with simian virus 40 T antibody.
The risk association between experimental portal hypertension and an aortic atherosclerosis-like disease
Authors: Salvatore Petta, Antonio Craxì
Journal: Hepatology (2012)

We thank Dr. de las Heras and colleagues for their interest in our recent paper.1 We recently found that patients with genotype 1 chronic hepatitis C (CHC) had a higher prevalence of carotid atherosclerosis compared with a control population, and identified older age and the presence of severe hepatic fibrosis as two factors independently associated with the presence of carotid plaques. According to these data, we speculated that the proinflammatory and profibrogenic environment prompting fibrogenesis in the liver of hepatitis C virus (HCV)-infected patients could also be systemically activated, enhancing the development of atherosclerotic lesions and explaining the higher prevalence of carotid plaques in this subgroup of CHC patients. Interestingly, Dr. de las Heras and colleagues suggest that other mechanism(s) could operate to explain the high prevalence of atherosclerotic disease in CHC. Specifically, in experimental studies on rats, they observed that induced long-term prehepatic portal hypertension (PH) led to development of a chronic inflammatory impairment of the abdominal aorta, rather than to the development of steatosis and dyslipidemia, which are potentially also responsible for the atherogenic pathogenic mechanism in the production of an aortic disease related to PH.2, 3 Although these results are interesting, they were obtained in experimental animals, and we were unable to validate them in our patients. In fact, in our study1 we enrolled patients with CHC (only 13 patients had cirrhosis) without significant PH and without data on portal pressure. Prospective studies aimed at evaluating the impact of PH on atherosclerotic lesions in HCV and non–HCV-infected patients with chronic liver diseases may be useful to assess the interesting finding suggested by Dr. de las Heras and colleagues. Salvatore Petta M.D., Ph.D.*, Antonio Craxì M.D.*, * Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
Psychiatry and the homeless mentally ill: a reply to Dr. Lamb
Authors: D Mossman, M L Perlin
Journal: American Journal of Psychiatry (1992)

Homeless mentally ill persons are highly visible subjects of ongoing public discussion and potent symbols of a host of contemporary social problems. They present psychiatry with a scientific challenge that calls for further elucidation of the sources of their mental illness and for fashioning possible solutions to their problems. They also present a moral challenge that requires psychiatrists to acknowledge the cultural, political, legal, and economic context of the mental problems of the homeless in the course of deciding what should be done to help them. H. Richard Lamb has proposed a program of aggressive outreach and psychiatric hospitalization for the homeless mentally ill. The authors believe that his proposal misconstrues the problems and needs of homeless mentally ill individuals; it would also needlessly infringe upon their freedom, further stigmatize them, and probably not help them. The authors offer an alternative understanding of the plight of the homeless mentally ill which places their problems within a larger context of social trends and domestic issues that society has been reluctant to confront. Psychiatrists can help the homeless mentally ill by championing their liberty rights and by focusing public discourse on the broad national need for improved access to medical and psychiatric care.
Psychosocial distress and well-being among gay and bisexual men with human immunodeficiency virus infection
Authors: H T Chuang, G M Devins, J Hunsley, M J Gill
Journal: American Journal of Psychiatry (1989)

The authors examined levels of psychosocial distress and well-being in 65 gay or bisexual men infected with the human immunodeficiency virus (HIV); 24 of these men had asymptomatic HIV infection, 22 had acquired immune deficiency syndrome (AIDS)-related complex, and 19 had AIDS. All of the men evidenced high levels of psychosocial distress, but those with AIDS-related complex and those with asymptomatic HIV infection were significantly more distressed than those with AIDS. Corresponding differences were not observed in feelings of psychosocial well-being. The authors conclude that specific psychosocial issues and adaptive demands should be identified over the course of HIV illness.