tbuckley/cabot-search huggingface dataset:
High-Dose Cytarabine Consolidation With or Without Additional Amsacrine and Mitoxantrone in Acute Myeloid Leukemia: Results of the Prospective Randomized AML2003 Trial
Authors: Markus Schaich, Stefani Parmentier, Michael Kramer, Thomas Illmer, Friedrich Stölzel, Christoph Röllig, Christian Thiede, Mathias Hänel, Kerstin Schäfer-Eckart, Walter Aulitzky, Hermann Einsele, Anthony D. Ho, Hubert Serve, Wolfgang E. Berdel, Jiri Mayer, Norbert Schmitz, Stefan W. Krause, Andreas Neubauer, Claudia D. Baldus, Johannes Schetelig, Martin Bornhäuser, Gerhard Ehninger
Journal: Journal of Clinical Oncology (2013)

To assess the treatment outcome benefit of multiagent consolidation in young adults with acute myeloid leukemia (AML) in a prospective, randomized, multicenter trial.Between December 2003 and November 2009, 1,179 patients (median age, 48 years; range, 16 to 60 years) with untreated AML were randomly assigned at diagnosis to receive either standard high-dose cytarabine consolidation with three cycles of 18 g/m(2) (3× HD-AraC) or multiagent consolidation with two cycles of mitoxantrone (30 mg/m(2)) plus cytarabine (12 g/m(2)) and one cycle of amsacrine (500 mg/m(2)) plus cytarabine (10 g/m(2); MAC/MAMAC/MAC). Allogeneic and autologous hematopoietic stem-cell transplantations were performed in a risk-adapted and priority-based manner.After double induction therapy using a 3 + 7 regimen including standard-dose cytarabine and daunorubicin, complete remission was achieved in 65% of patients. In the primary efficacy population of patients evaluable for consolidation outcomes, consolidation with either 3× HD-AraC or MAC/MAMC/MAC did not result in any significant difference in 3-year overall (69% v 64%; P = .18) or disease-free survival (46% v 48%; P = .99) according to the intention-to-treat analysis. Furthermore, MAC/MAMAC/MAC led to additional GI and hepatic toxicity and a higher rate of infection and bleeding, resulting in significantly shorter 3-year overall survival in the per-protocol analysis compared with 3× HD-AraC (63% v 72%; P = .04).In younger adults with AML, multiagent consolidation using mitoxantrone and amsacrine in combination with high-dose cytarabine does not improve treatment outcome and confers additional toxicity.
Life and Death and Medicine
Authors: Glen W. Davidson
Journal: JAMA (1974)

<i>Scientific American</i>has published a single-topic issue for the past 24 years. This volume is the hard-back edition of the September 1973 issue that focused on the "crisis" in American health services. The editors identify the crisis as the chronic "long-term, deep-running changes in the medical economy that are proceeding in the main without direction from plan or policy." Certainly no one can any longer ignore the crescendo of debate about rising expectations, and costs, of health care. However, what is often missed is the profound changes in perspectives, values, and institutions that are also part of the crisis. So often, it seems that those of us in the health professions calculate the impact of change only in terms of efficiency, effectiveness, or economy. It takes historians in each age to translate the facts of change into implications for living. The 13 chroniclers in this volume have done a good
A dual role of p21 in liver regeneration and hepatocarcinogenesis
Authors: Christian Liedtke, Christian Trautwein
Journal: Hepatology (2008)

Willenbring H, Sharma AD, Vogel A, Lee AY, Rothfuss A, Wang Z, Finegold M, Grompe M. Loss of p21 permits carcinogenesis from chronically damaged liver and kidney epithelial cells despite unchecked apoptosis. Cancer Cell 2008;14:59-67 (Reprinted with permission). Abstract Accumulation of toxic metabolites in hereditary tyrosinemia type I (HT1) patients leads to chronic DNA damage and the highest risk for hepatocellular carcinomas (HCCs) of any human disease. Here we show that hepatocytes of HT1 mice exhibit a profound cell-cycle arrest that, despite concomitant apoptosis resistance, causes mortality from impaired liver regeneration. However, additional loss of p21 in HT1 mice restores the proliferative capabilities of hepatocytes and renal proximal tubular cells. This growth response compensates cell loss due to uninhibited apoptosis and enables animal survival but rapidly leads to HCCs, renal cysts, and renal carcinomas. Thus, p21's antiproliferative function is indispensable for the suppression of carcinogenesis from chronically injured liver and renal epithelial cells and cannot be compensated by apoptosis.
Radium Ra 223 Dichloride Injection: U.S. Food and Drug Administration Drug Approval Summary
Authors: Paul G. Kluetz, William Pierce, V. Ellen Maher, Hui Zhang, Shenghui Tang, Pengfei Song, Qi Liu, Martin T. Haber, Eldon E. Leutzinger, Ali Al-Hakim, Wei Chen, Todd Palmby, Elleni Alebachew, Rajeshwari Sridhara, Amna Ibrahim, Robert Justice, Richard Pazdur
Journal: Clinical Cancer Research (2013)

On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo injection; Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either Ra-223 plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR, 0.70; 95% confidence interval, 0.55-0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (>10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (>10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Ra-223 is the first α-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer.
A novel pathway for biosynthesis of cholestanol with 7 alpha-hydroxylated C27-steroids as intermediates, and its importance for the accumulation of cholestanol in cerebrotendinous xanthomatosis.
Authors: S Skrede, I Björkhem, M S Buchmann, G Hopen, O Fausa
Journal: Journal of Clinical Investigation (1985)

A mixture of 7 alpha-3H- and 4-14C-labeled cholesterol was administered intravenously to rats. Cholestanol with 20-30% lower ratio between 3H and 14C than in cholesterol could be isolated from different organs. In a healthy human control, cholestanol isolated from feces had a 3H/14C ratio which was 28% lower than in administered cholesterol. Cholesterol and coprostanol reisolated in these experiments had the same ratio between 3H and 14C as in the precursor. A previously unknown pathway for formation of cholestanol, involving 7 alpha-hydroxylated intermediates, may explain these results. Under normal conditions, this pathway is responsible for at most 30% of the cholestanol synthesized from cholesterol. Intravenous administration of the 7 alpha-3H- and 4-14C-labeled cholesterol to a patient with cerebrotendinous xanthomatosis (CTX) resulted in formation of cholestanol which had 70-75% lower 3H/14C ratio. It is concluded that the novel pathway involving 7 alpha-hydroxylated intermediates is accelerated in patients with CTX. This acceleration may contribute essentially to the accumulation of cholestanol, which is a predominant feature of this disease. 7 alpha-Hydroxycholesterol and 7 alpha-hydroxy-4-cholesten-3-one might be intermediates in the novel pathway to cholestanol. After intravenous administration of 7 beta-3H-labeled 7 alpha-hydroxycholesterol in a patient with CTX, significant amounts of 3H were incorporated into plasma and fecal cholestanol. Only small amounts of 7 alpha-hydroxycholesterol and 7 alpha-hydroxy-4-cholesten-3-one are excreted into the intestine, and we therefore conclude that the 7 alpha-dehydroxylation step mainly occurs in the liver. In CTX, the synthesis of cholestanol may be accelerated because the concentrations of 7 alpha-hydroxylated bile acid intermediates in the liver are increased. A possible mechanism for the conversion of a minor fraction of 7 alpha-hydroxycholesterol into cholestanol is suggested.
TREATMENT OF PUERPERAL SEPSIS
Authors: C. H. Roberts, J. B. Banister, A. W. Bourne, T. B. Davies, L. C. Rivett, L. Phillips, C. S. Lane-Roberts
Journal: BMJ (1924)

OBJECTIVES: To assess the effects that the recent seasonal change in rugby league from winter to summer has had on the incidence of injury. METHODS: All injuries that occurred during games and training were recorded throughout four consecutive seasons (three winter, one summer) for the first team squad of a British professional rugby league club. Data included nature of injury, days lost as the result of injury, player position, month, and season. RESULTS: An increasing incidence of injury over the four seasons was observed, with the summer seasons having an incidence almost double that of the first winter season recorded (696.8 per 1000 hours and 363.55 per 1000 hours respectively). The severity of injury was shown to decline over the four seasons. Most injuries were incurred in matches (74.9%) rather than during training (25.1%). CONCLUSIONS: The findings show an increasing incidence of injury in summer rugby but with decreased severity. It is not known if this is the result of playing back to back rugby seasons or is a consequence of a change in playing season and ground conditions.
Russian Surgeon Operates Without Preanesthetic Medication
Authors: Alexander Solosko
Journal: JAMA (1961)

<h3>To the Editor:—</h3> During the past year, there were numerous reports and references inThe Journalon preanesthetic medication, a majority of which concerned the so-called advantages of one drug over another. Last June I had the opportunity to observe surgery in a hospital of the Soviet Union, and what I learned there concerning premedication prior to surgery may be of general interest. I was sitting in the office of Professor P. I. Androsov, in the Sklysoforsky Institute of Moscow. He is one of Russia's topflight surgeons and, I believe, the inventor of their blood vessel—stapling apparatus. While we were discussing medical practices—waiting for the operating room to be set up for a gastrectomy—one of his physician assistants intimated that they were ready. On our way to the operating room, we passed a thin Russian, who appeared to be about 35 years of age. He was dressed in pajamas, wore slippers
CAN ECHOCARDIOGRAPHIC EVALUATION OF CARDIOPULMONARY HEMODYNAMICS REPLACE RIGHT HEART CATHETERIZATION IN END-STAGE HEART FAILURE PATIENTS AWAITING TRANSPLANTATION?
Authors: Suman Kuppahally, Edward M. Gilbert, Sheldon E. Litwin, Stephen M. Ishihara, Renee Neuharth, Andrew D. Michaels, Anwar Tandar, Feras Bader
Journal: Journal of the American College of Cardiology (2010)
Analysis of environmental and biologic methyl parathion data to improve future data collection.
Authors: Rubina Imtiaz, Gilbert Haugh
Journal: Environmental Health Perspectives (2002)

The Agency for Toxic Substances and Disease Registry analyzed concurrently collected data on environmental methyl parathion (MP) and urinary p-nitrophenol (PNP) at the request of the U.S. Environmental Protection Agency (U.S. EPA). The purpose of the analysis was to assess whether individuals' age or level of residential MP contamination might predict their urinary PNP level. Unlicensed pesticide applicators had sprayed residences in Mississippi with MP, which is approved as a pesticide only for outdoor agricultural use. Data were received from Mississippi for MP wipe sample levels for 409 homes and urinary PNP levels for 929 residents of the residences sampled. In addition to descriptive and bivariate analyses, ordinal logistic regression was performed after categorizing the data. Interpretation of results was limited by several identified data gaps and pre-existing data-quality issues. On the basis of the lessons learned from identified data gaps, specific recommendations were made to the U.S. EPA for improving future data collection methods for more meaningful exposure assessment in similar environmental contaminations. The recommended changes were successfully incorporated in subsequent data collected by other states that had experienced similar residential MP spraying.
Metastatic Embryonal Rhabdomyosarcoma to the Pancreas Presenting as Acute Pancreatitis Detected by FDG PET/CT
Authors: Jigang Yang, Ion Codreanu, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2012)

An 8-year-old boy with history of embryonal rhabdomyosarcoma resected 2 years ago presented with abdominal pain and elevated pancreatic enzymes. Acute pancreatitis was diagnosed, and appropriate therapy was started. An FDG PET/CT scan revealed a hypermetabolic region in the pancreas suspicious for malignancy; however, the patient's condition improved after therapy. A repeat PET/CT scan performed 3 weeks later for recurrent symptoms showed interval disease progression, consistent with metastatic disease. Our case indicates that pancreatitis can accompany malignancy or be related to the obstruction caused by tumor, and patient's response to therapy for acute pancreatitis does not rule out malignancy.
Estrogen Modulates Inflammatory Mediator Expression and Neutrophil Chemotaxis in Injured Arteries
Authors: Andrew P. Miller, Wenguang Feng, Dongqi Xing, Nathaniel M. Weathington, J. Edwin Blalock, Yiu-Fai Chen, Suzanne Oparil
Journal: Circulation (2004)

Background— We have previously shown that estrogen (17β-estradiol; E2) inhibits neointima formation and migration of leukocytes, particularly neutrophils, into rat carotid arteries after acute endoluminal injury. This study tested the hypothesis that E2 inhibits expression of adhesion molecules, chemokines, and proinflammatory cytokines in rat carotid arteries in the early hours after balloon injury, thus attenuating the stimulus for leukocyte entry and negatively modulating the injury response. Methods and Results— Ovariectomized (OVX) rats were randomly assigned to treatment with E2 or vehicle (V) and subjected to balloon injury of the right carotid artery. After 2, 6, and 24 hours, rats were euthanized, and both carotid arteries were processed for real-time reverse transcription–polymerase chain reaction (2 and 24 hours), ELISA (6 hours), or neutrophil chemotaxis assay (24 hours). Expression of mRNA for adhesion molecules (P-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1), chemoattractants (cytokine-induced neutrophil chemoattractant [CINC]-2β and monocyte chemoattractant protein [MCP]-1), and proinflammatory cytokines (interleukin [IL]-1 and IL-6) was markedly increased (2 to 5000 times) in injured arteries of OVX+V rats at 2 hours and was reduced by 24 hours. E2 significantly attenuated expression of the proinflammatory mediators (by 60% to 80%) at 2 hours. ELISA confirmed injury-induced upregulation of neutrophil and monocyte/macrophage chemoattractants (CINC-2α, MCP-1) in OVX+V arteries and E2-induced inhibition of CINC-2α expression. E2 significantly (by 65%) inhibited neutrophil chemotactic activity of arterial homogenates. Conclusions— E2 attenuates the early vascular injury response, at least in part, by negatively modulating proinflammatory mediator expression and the resultant chemotactic activity of injured vessels for neutrophils.
Spleen tyrosine kinase (Syk) is a potent target for GvHD prevention at different cellular levels
Authors: F Leonhardt, K Zirlik, M Buchner, G Prinz, A-K Hechinger, U V Gerlach, P Fisch, A Schmitt-Gräff, W Reichardt, R Zeiser
Journal: Leukemia (2012)
<i>EML4-ALK</i> Fusion Gene Assessment Using Metastatic Lymph Node Samples Obtained by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Authors: Yuichi Sakairi, Takahiro Nakajima, Kazuhiro Yasufuku, Dai Ikebe, Hajime Kageyama, Manabu Soda, Kengo Takeuchi, Makiko Itami, Toshihiko Iizasa, Ichiro Yoshino, Hiroyuki Mano, Hideki Kimura
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes for non–small cell lung cancers (NSCLC). Several ALK inhibitors have been developed, and are now being evaluated in ALK-positive NSCLC. The feasibility of detecting ALK fusion genes in samples obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was determined. The clinicopathologic characteristics of ALK-positive lung cancer were also analyzed. Experimental Design: From April 2008 to July 2009, NSCLC cases with hilar/mediastinal lymph node metastases detected by EBUS-TBNA were enrolled. Positive expression of ALK fusion protein was determined using immunohistochemistry, and ALK gene rearrangements were further examined to verify the translocation between ALK and partner genes using fluorescent in situ hybridization and reverse transcription-PCR. Direct sequencing of PCR products was performed to identify ALK fusion variants. Results: One hundred and nine cases were eligible for the analysis using re-sliced samples. Screening of these specimens with immunohistochemistry revealed ALK positivity in seven cases (6.4%), all of which possessed echinoderm microtubule–associated protein-like 4–ALK fusion genes as detected by fluorescent in situ hybridization and reverse transcription-PCR. All ALK-positive cases had an adenocarcinoma histology and possessed no EGFR mutations. Compared with ALK-negative cases, ALK-positive cases were more likely to have smaller primary tumors (P &amp;lt; 0.05), to occur at a younger age (&amp;lt;60 years; P &amp;lt; 0.05), and to occur in never/light smokers (smoking index &amp;lt; 400; P &amp;lt; 0.01). Mucin production was frequently observed in ALK-positive adenocarcinomas (29.4%; P &amp;lt; 0.01). Conclusions: EBUS-TBNA is a practical and feasible method for obtaining tissue from mediastinal and hilar lymph nodes that can be subjected to multimodal analysis of ALK fusion genes in NSCLC. Clin Cancer Res; 16(20); 4938–45. ©2010 AACR.
FDA restricts use of one intraocular lens type
Authors: John Elliott
Journal: JAMA (1980)

The Food and Drug Administration has moved to restrict the use of a particular type of intraocular lens implant—the anterior chamber angle support lens— despite the recent conclusion by a panel of expert ophthalmologists that this intraocular lens type and three others commonly used all yield "significant visual advantages." (That appraisal was made this past fall at a consensus development conference on intraocular lenses sponsored by the National Institutes of Health [<i>JAMA</i>(MEDICAL NEWS) 242:2047-2053, 1979].) In a statement, new FDA chief Jere Goyan, PhD, announced that only physicians who have implanted anterior chamber lenses in the past will be allowed to do so in the future. In addition, the agency will conduct special inspections of the plants where the anterior chamber lenses are made and will conduct its own laboratory analyses of the lenses. The anterior chamber lens is secured in the eye by wedging the device between the front
Infiltration of the Spinal Cord in a Patient With Multiple Myeloma
Authors: Marzia Varettoni, Alessandro Corso, Patrizia Zappasodi, Fabrizio Calliada, Carlo Castagnola, Silvia Mangiacavalli, Mario Lazzarino
Journal: Journal of Clinical Oncology (2008)

therapy with erlotinib.In this exceptional case, previous oncological treatment precluded conventional chemoradiotherapy and compelled for inventive treatment strategies, using both conventional and novel treatment options in an optimal way.Selection of the proper patients for treatment with EGFR-TKIs remains crucial. 1 The response of NSCLC to treatment with erlotinib can be fast, with a near complete pathological response achieved by only 3 weeks of treatment.As with chemotherapy, the pathological response to EGFR inhibitors can be underestimated by PET and CT scan.Accurate and additional pathological staining methods may be needed to differentiate complete from near-complete pathological responses.To investigate the role of EGFR-TKIs in treatment of early stage NSCLC, a phase II study has been initiated in the Netherlands.This open-label prospective study will investigate the effect of erlotinib as an induction treatment in both selected (based on two or more of the following characteristics: female, nonsmoker, adenocarcinoma, or Asian) and unselected patients with operable stage I/II NSCLC, and will address both clinical and translational topics.Although up until now no data supported the use of EGFR-TKIs as neoadjuvant therapy in stage I-IIIA NSCLC, their low toxicity profile and the possibility of rapid tumor response suggests that this form of therapy may be used for induction therapy.Obviously treatment-related changes in resected tumor samples will be an important end point of this trial.
Signal Transducer and Activator of Transcription 6 Controls Chemokine Production and T Helper Cell Type 2 Cell Trafficking in Allergic Pulmonary Inflammation
Authors: Anuja Mathew, James A. MacLean, Elliot DeHaan, Andrew M. Tager, Francis H.Y. Green, Andrew D. Luster
Journal: The Journal of Experimental Medicine (2001)

Antigen-specific CD4 T helper type 2 (Th2) cells play a pivotal role in the induction of allergic asthma, but the mechanisms regulating their recruitment into the airways are unknown. Signal transducer and activator of transcription factor (Stat)6 is a transcription factor essential for Th2 cell differentiation. Here we show that Stat6 also controls Th2 cell recruitment and effector function in allergic inflammation in vivo. To isolate the role of Stat6 in regulating Th2 cell trafficking and effector function from its role in Th2 cell differentiation, we used a murine model of asthma in which in vitro–differentiated Stat6+/+ antigen-specific Th2 cells were adoptively transferred into naive Stat6−/− and Stat6+/+ mice followed by aerosol antigen challenge. We found that all of the features of asthma, including Th2 cell accumulation, Th2 and eosinophil-active chemokine production, and airway eosinophilia, mucus production, and hyperresponsiveness seen in Stat6+/+ mice, were dramatically absent in Stat6−/− mice that received Stat6+/+ antigen-specific Th2 cells. Our findings establish Stat6 as essential for Th2 cell trafficking and effector function and suggest that interruption of Stat6 signaling in resident cells of the lung is a novel approach to asthma therapy.
Hypoglycemia Resulting from Insecticide Poisoning-Reply
Authors: Zdenek Hruban
Journal: JAMA (1963)

It is indeed unfortunate that there is a highly charged atmosphere concerning pesticides. However, it is our contention that the air could best be cleared by accumulation of scientific data. Suppression of information, even if it is circumstantial, will not help to solve this problem nor save any lives. Although books have been written on parathion, its effect on blood sugar has never been investigated. There are numerous other instances, in which biochemical or physiological effects of a drug or poison escaped detection during animal experimentation or did not occur in the species studied. We are aware that these data are only a first approach to the problem of chronic and acute effects of parathion on the blood sugar of animals and man. The major purpose of the article is to stimulate accumulation of more data on the possible exposure to insecticides in patients with hypoglycemia and on the role
Isabel Mary Headen (Gardner) (nee Woodhouse)
Authors: I. Headen
Journal: BMJ (2010)

Isabel Mary Headen (Gardner) (nee Woodhouse) was one of those women who longed to demonstrate that men and women doctors have equal but different gifts and attributes. Widowed at 42 with four young daughters, she courageously mothered them and dedicated herself to fulltime work.

She worked in general practice, blood transfusion, school health, community medicine, …