tbuckley/cabot-search huggingface dataset:
P12 Pirfenidone post-authorisation safety registry (PASSPORT) – update and concomitant use of N-acetylcysteine and/or corticosteroids
Authors: T Maher, V Cottin, A Azuma, L Groves, P Hormel, M Sköld, S Tomassetti, D Koschel
Journal: Thorax (2015)

<h3>Background</h3> PASSPORT is a post-authorisation safety registry for pirfenidone to collect real-world data in EU patients with idiopathic pulmonary fibrosis (IPF). This analysis assessed the safety of pirfenidone as monotherapy and in combination with N-acetylcysteine (NAC) and/or corticosteroids (CS). <h3>Methods</h3> 109 EU sites dosed 1006 patients. Safety data were recorded at routine clinic visits for up to 2 years. Pirfenidone-associated adverse drug reactions (ADR) were collected. <h3>Results</h3> At baseline, mean±SD age was 70 ± 8.5 years and mean±SD time since IPF diagnosis was 1.6 ± 2.5 years; 80% of patients were male; supplemental oxygen was used by 27% of patients; mean±SD FVC was 2.56 ± 0.78 L; mean±SD% predicted FVC was 66 ± 16% (14% had &lt;50% predicted FVC). The most common comorbidities (&gt;10%) were hypertension, gastroesophageal reflux disease, hypercholesterolemia and coronary artery disease. At this interim analysis, median time on pirfenidone was 7.6 months and total exposure was 803 patient-years. Overall, 67% of patients had ≥1 ADR, most commonly: nausea, 17%; fatigue, 15%; decreased appetite, 13%; decreased weight, 12%; rash, 10%; and diarrhoea, 9%. Of patients who had an ADR, 55% experienced their first ADR within the first 30 days’ treatment. Around 5% of patients completed 2 years’ treatment, 55% are ongoing, 9% died and 21% discontinued due to pirfenidone-related ADRs (most commonly nausea, rash and decreased weight). 11% discontinued for other reasons. Patients with FVC &lt;50% had a higher discontinuation rate than other patients (48% vs 39%, respectively). The imbalance was mainly driven by higher rates of death and lung transplantation. The discontinuation rate due to pirfenidone ADRs was similar among patients with FVC &lt;50% and ≥50% (20.3% vs 20.9%, respectively). 62% of patients received pirfenidone alone; 11%, 8% and 8% received pirfenidone plus NAC, CS, or NAC+CS, respectively. The remaining 11% had partial use of NAC and/or steroids. ADR incidence was generally consistent for these subgroups except weight decrease and ALT increase, which occurred more often in the pirfenidone+CS group. <h3>Conclusions</h3> In this real-world setting, pirfenidone was generally safe and well tolerated as monotherapy or combined with NAC and/or CS. The rate of discontinuation due to pirfenidone-related ADRs was similar regardless of disease severity.
Comorbidity in mania at first hospitalization
Authors: S M Strakowski, M Tohen, A L Stoll, G L Faedda, D C Goodwin
Journal: American Journal of Psychiatry (1992)

Comorbidity was studied in 41 manic and mixed-state bipolar patients at first hospitalization. The lifetime prevalence of comorbidity was high; 21 subjects (51.2%) had at least one other psychiatric diagnosis (N = 16, 39.0%) or medical disorder (N = 9, 22.0%). Nine subjects had multiple comorbid diagnoses. Women were 2.7 times more likely to have a comorbid diagnosis. The presence of comorbidity was not associated with differences in outcome measures.
Chylopericardium with Multiple Lymphangioma of Bone
Authors: Marvin R. Goldstein, A. Benchimol, William Cornell, David R. Long
Journal: New England Journal of Medicine (1969)

Multiple lymphangiomas of bone occurred in association with asymptomatic chylopericardium secondary to mediastinal lymphangioma. This combination, not previously reported, may represent a generalized abnormality of the lymphatic system.
Characteristics of True-Positive and False-Positive Results of Electrocardiographs Master Two-Step Exercise Tests
Authors: E. Lepeschkin, B. Surawicz
Journal: New England Journal of Medicine (1958)

THE electrocardiographic exercise test is a well established procedure in the diagnosis of coronary insufficiency. The method most widely used in America is the two-step test of Master.1 2 3 4 5 6 Master has standardized the exercise for the individual subject on the basis of sex, age and weight. One of the objections raised against the procedure was that the exercise was of short duration and did not permit the achievement of a steady state. However, the results of a recently published comparative study between the double Master two-step test and the exercise on a treadmill, which was sufficiently long to achieve the steady . . .
Excessive Blood Drawing for Laboratory Tests
Authors: Jocelyn M. Hicks
Journal: New England Journal of Medicine (1999)

To the Editor: I was recently hospitalized in a major university hospital for the Guillain–Barre syndrome. While there, I had blood drawn, usually twice a day. During my two weeks in the intensive care unit, my hematocrit dropped from 43 to 31. As chair of the Department of Laboratory Medicine at a well-known children's teaching hospital, I was shocked at the amount of blood drawn for my tests. I asked the phlebotomist to draw less blood, but she refused, saying that her instructions had to be followed. While I was completely paralyzed, I began to think about why hospitals draw . . .
First in human phase I study of BSI-201, a small molecule inhibitor of poly ADP-ribose polymerase (PARP) in subjects with advanced solid tumors
Authors: S. Kopetz, M. M. Mita, I. Mok, K. K. Sankhala, J. Moseley, B. M. Sherman, C. R. Bradley, A. W. Tolcher
Journal: Journal of Clinical Oncology (2008)

3577 Background: PARP is a critical enzyme of cell proliferation and DNA repair. BSI-201 is a small molecule believed to achieve its anti-neoplastic effect by covalently binding and inhibiting PARP-1. When given as a single agent and in combination with other cytotoxic agents, BSI-201 is active against a broad range of cancer cells in culture, including drug resistant cell lines. Methods: Eligible subjects were≥ 18 years old with a refractory, advanced solid tumor, had ECOG PS of ≤ 2, and had adequate hematological, renal, and hepatic function. Starting at a dose of 0.5 mg/kg given IV twice weekly, BSI-201 dose escalations were carried out via a traditional '3 + 3' design, with increases guided by observed toxicities. Pharmacokinetic samples were taken, and PARP inhibition measured in peripheral blood mononuclear cells (PBMCs). Tumor response was determined using RECIST criteria at 8 week intervals. Results: 23 subjects have been treated at 7 dose levels ranging from 0.5 mg/kg to 8.0 mg/kg. All doses were well tolerated without an identified maximum tolerated dose. The most common adverse event (AE) categories were: gastrointestinal disorders (39% of AEs), general disorders (21%), and respiratory (7%). A BSI-201 dose of 1.4 mg/kg resulted in a Cmax of 400 ng/mL or higher, well above concentrations associated with efficacy in pre-clinical models (20–30 ng/mL). BSI-201 was rapidly eliminated (t ½ = 4 min), with longer lived metabolites indicative of an active intermediate. At the fifth dose level of 2.8 mg/kg, PARP was inhibited in PBMCs by greater than 50% after a single dose, with greater inhibition observed (80% or more) after multiple dosing, consistent with the formation of a covalently bound nitroso metabolite. Best response of stable disease for 2 months or more was seen for 6/23 subjects in this heavily pre-treated population (mean # of prior regimens > 6), with 1 subject on study for over 9 months. Conclusions: BSI-201 is safe and well tolerated at all doses studied. A biologically relevant dose was identified via estimation by pharmacodynamic endpoints and through exceeding effective preclinical concentrations in serum. Further exploration of BSI-201 in combination with other chemotherapeutic agents is warranted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration BiPar Sciences BiPar Sciences BiPar Sciences
First-Line Chemotherapy for Patients with Gastroesophageal Adenocarcinoma in the Community Setting: a Multicenter Cohort of 418 Patients
Authors: M. Garrido, M.A. Vicente Conesa, A. Carmona-Bayonas, L. Faez, A. Custodio, C. Lopez, L. Visa, J. Gallego Plazas, S. Fernandez Arrojo, A. Ramchandani, M. Múgica, C. Murias, V. Iranzo, E. Buxo, N. Hindi, F. Erpel, E. Pineda, E. Jofré, C. Giraldo, P. Jimenez Fonseca
Journal: Annals of Oncology (2014)
PTPS-27NON-GERMINOMATOUS GERM CELL TUMORS WITH SYNCHRONOUS PINEAL AND SUPRASELLAR INVOLVEMENT
Authors: Hung Tran, Nikita Dhir, Ashley Margol, Nathan Robison, Jyotsana Kemani, Kenneth Wong, Anna Evans, Mary Nelson, John Grimm, Jonathan Finlay, Girish Dhall
Journal: Neuro-Oncology (2015)

PURPOSE: Bifocal presentation of central nervous system (CNS) germinomas, with synchronous pineal and suprasellar involvement, is common, and associated with favorable outcome. However, the incidence and outcome of bifocal presentation of non-germinomatous germ cell tumors (NGGCT) is less well described. METHODS: Medical records of patients with CNS NGGCT treated at Children's Hospital Los Angeles between 1993 and 2014 were reviewed for clinical characteristics, treatment and outcome. RESULTS: Seven (24.1%) of 29 patients diagnosed with CNS NGGCT between 1993 and 2014 had bifocal involvement. The mean age at diagnosis was 13.1 years (range: 8-22 years). Diagnosis was made on tumor marker elevation in seven patients, and confirmed on histopathology on one patient. Seven patients had elevated AFP and one patient had elevated βHCG in serum and/or CSF. Two patients are still undergoing therapy and have not been included in the survival analyses. Four of remaining five patients are long term survivors at 41, 56, 57, and 97 months. Patient #1 received initial chemotherapy without irradiation, relapsed in the 3rd ventricle at 10 months, and was successfully salvaged with high-dose chemotherapy (HDCx) with autologous hematopoietic stem cell rescue (AuHCR) and 3600cGy craniospinal irradiation (CSI) with local boost. Patient #2 had partial response to chemotherapy, underwent HDCx and AuHCR, followed by 3600cGy CSI with boost. Patients #3 and #4 received chemotherapy with a complete response, followed by whole ventricular irradiation with a local boost. Patient #5 received chemotherapy only, developed ventricular relapse at 75 months, was treated with cyclophosphamide and vinblastine followed by CSI with boost, but died at 87 months. CONCLUSIONS: Our experience suggests that bifocal NGGCT may be more common than previously thought, and may be more likely to have yolk-sac component given elevated AFP, and therefore have a better prognosis than other NGGCT.
Soft Tissue Sarcoma Risk in Swedish Agricultural and Forestry Workers&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K Wiklund, L E Holm
Journal: JNCI Journal of the National Cancer Institute (1986)

The risk of soft tissue sarcoma following possible exposure to phenoxy acid herbicides was studied in 354,620 Swedish men, who were employed in agriculture or forestry according to a national census in 1960. This cohort was further divided into six subcohorts, on assumed exposure to phenoxy acid herbicides. The most commonly used phenoxy acid in Sweden was (4-chloro-2-methylphenoxy)acetic acid (CAS: 94-74-6). The reference cohort encompassed 1,725,845 Swedish men employed in other industries. All persons were followed up in the cancer-environment register during the period 1961-79. A total of 331 cases of soft tissue sarcomas was observed in the study cohort and there were 1,508 cases in the reference group [relative risk (RR), 0.9; 95% confidence interval, 0.8-1.0]. No subcohort of agricultural or forestry workers showed any significantly increased RR, nor was there any significant difference in RR between the subcohorts. Despite the greatly increased use of phenoxy acid herbicides from 1947 to 1970, no time-related increase in the RR of soft tissue sarcoma was found in the total cohort or in any of the subcohorts.
Torsion of Previously Normal Tube and Ovary in Children
Authors: Loyd R. Schultz, William A. Newton, H. William Clatworthy
Journal: New England Journal of Medicine (1963)

TORSION of ovarian cysts and tumors occurs often enough for most physicians to be well aware of this entity. That torsion of previously normal ovaries occurs is not so widely known. Because of its rarity, we consider it justified to report the cases of 5 children who were treated for torsion of previously normal adnexal structures at the Children's Hospital, Columbus, Ohio, in a ten-year period between May 1952 and 1962. The involved ovary and tube were removed in each of these cases. During a similar ten-year period, 6 cysts and 10 solid tumors of the ovary were seen at . . .
Proximal Coronary-Artery Obstruction
Authors: John E. Connolly, Frederic L. Eldridge, James W. Calvin, Edward A. Stemmer
Journal: New England Journal of Medicine (1964)

THE correction of coronary-artery obliterative disease remains one of the most challenging and as yet unrealized goals in cardiac surgery. Although many operations to supply blood to the myocardium distal to obstructed coronary arteries have been advocated,1 , 2 none have found an established place in the vascular surgeon's armamentarium. The direct surgical approaches to the problem by Bailey arid May3 and Cannon and Longmire4 , 5 in 1957 and 1958 were thus greeted with great enthusiasm arid widespread interest. However, after initial promise, few successful applications of the direct endarterectomy approach to obstruction of the coronary artery have been reported.6 This appears to . . .
Bleeding Tendency in Uremia
Authors: Charles E. Rath, James A. Mailliard, George E. Schreiner
Journal: New England Journal of Medicine (1957)

ALTHOUGH abnormal bleeding has been known to occur as a complication of renal failure at least since the time of Bright (1827) surprisingly little attention has been paid to this problem. A recent monograph on coagulation1 assigns four sentences to bleeding in uremia. As mentioned by Larrain,2 a recent comprehensive review3 on the management of acute renal failure does not mention bleeding as a possible complication.Riesman,4 writing in 1907, appears to have been the first to recognize renal disease as the cause of a hemorrhagic diathesis. Other authors believed that the hemorrhagic diathesis caused the renal disease, or resulted . . .
Prevalence of pulmonary arterial hypertension in hepatic liver transplant candidates in Santa Casa Hospital
Authors: Eduardo Garcia, Fernanda Waltrick Martins, Taiane Francieli Rebelatto, Lucas Jesus de Medeiros, Rangel Oslen de Carvalho, Ajácio Brandão
Journal: European Respiratory Journal (2011)

Background:  Portopulmonary hypertension (PPH) is defined by the presence of pulmonary arterial hypertension, comprehending mean pulmonary artery pressure (mPAP) > 25 mmHg at rest and pulmonary vascular resistance > 120 dinas/seg/cm5, in association with severe liver disease or portal hypertension. PPH has important implications for the prognosis of chronic liver disease patients. The prevalence of PPH is conflicting in medical literature, ranging from 2 to 9% in larger studies.   Objectives:  To estimate the prevalence and severity of pulmonary hypertension in patients with severe liver disease or portal hypertension.   Methods:  Retrospective cross sectional review of 390 medical records regarding 375 patients with chronic liver disease undergoing liver transplantation at Santa Casa Hospital (Porto Alegre- Brazil), from February 2002 to April 2009. Fifteen patient records whose patients underwent retransplantation were excluded, as well as 31 patient records which lack information. The final sample had 344 patients. The present study was approved by the Hospital Ethics Committee. During the liver transplantation procedure, it was performed the pulmonary artery catheterization, and it has been made the measurement of the mPAP.   Results:  The patients mean age was 52.9 years old (14-74) and male gender comprised 62.8% (n = 216) of this sample. The prevalence of PPH was 10.2% (n = 35). Seventy seven per cent (n = 27) were classified as having mild PPH (mPAP 25 - 35mmHg) and 23% (n = 8) as moderate (36-50mmHg). The mean mPAP was 20.7 mmHg.   Conclusion:  The studied sample showed a slight increase in the prevalence of pulmonary hypertension when compared to former data in literature.
Abstract 1317: Biomarker evaluation for PD-1 targeted therapies in non-small cell lung cancer (NSCLC) patients
Authors: Alice O. Kamphorst, Rathi N. Pillai, Shu Yang, Rama Akondy, Lydia Koenig, Ke Yu, Megan McCausland, Gabriel Sica, Fadlo R. Khuri, Taofeek K. Owonikoko, Suresh S. Ramalingam, Rafi Ahmed
Journal: Cancer Research (2015)

Abstract Sustained expression of programmed cell death (PD)-1 inhibitory receptor is a hallmark of exhausted T cells during chronic infections and cancer. PD-1 signaling inhibits T cell activation, and maintains T cells in a dysfunctional state. Notably, inhibition of PD-1 interactions with PD-L1 is able to restore function in exhausted T cells. Several clinical trials have now shown that PD-1 blockade therapy results in durable clinical benefits in advanced stage cancer patients refractory to other treatments, and efficacy has been reported in multiple tumor types. Nonetheless many patients do not respond to PD-1 targeted therapies, hence a better understanding of the immunological responses induced by PD-1 pathway blockade and identification of predictive biomarkers is imperative. In this ongoing study we have analyzed peripheral blood mononuclear cells (PBMC) from advanced stage NSCLC patients, before and during the course of PD-1 pathway blockade therapy. We find that CD8 T cell activation is observed in some patients following therapy, but it is not consistently associated with clinical response. Interestingly, treatment-induced CD8 T cell proliferation is not sustained in some patients even with continuation of therapy. After PD-1 pathway blockade, we find co-expression of CTLA-4 on proliferating PD-1+ CD8 T cells in the blood. Accordingly, we found that tumor infiltrating CD8 T cells expressing high levels of PD-1 also co-express CTLA-4 (and Tim-3) in surgical specimens of patients with NSCLC. We will present additional data on CD8 and CD4 T cells in NSCLC patients enrolled in PD-1 targeted therapies clinical trials and discuss potential biomarkers. We conclude that peripheral blood analysis can provide valuable insights into anti-cancer effects of PD-1 targeted therapy. Citation Format: Alice O. Kamphorst, Rathi N. Pillai, Shu Yang, Rama Akondy, Lydia Koenig, Ke Yu, Megan McCausland, Gabriel Sica, Fadlo R. Khuri, Taofeek K. Owonikoko, Suresh S. Ramalingam, Rafi Ahmed. Biomarker evaluation for PD-1 targeted therapies in non-small cell lung cancer (NSCLC) patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1317. doi:10.1158/1538-7445.AM2015-1317
Characterization of Precipitating Antibodies to Ruminant Serum and Milk Proteins in Humans with Selective IgA Deficiency
Authors: Carolyn C. Huntley, John B. Robbins, Anne D. Lyerly, Rebecca H. Buckley
Journal: New England Journal of Medicine (1971)

Serums from 23 patients with isolated IgA deficiency contained precipitating antibodies to ruminant IgM proteins. Purified IgM proteins from bovine serum as well as similar proteins in other ruminant (goat, sheep, deer and elk) serum and in cow's milk reacted with the patient serum. IgA-deficient serum did not precipitate serum proteins from humans, nonhuman primates or numerous other animals. Patients with diseases reported to be associated with milk precipitins (e.g., Down's and Heiner's syndromes) may or may not have this factor in addition to antibodies directed toward other bovine milk and serum proteins. Because of the increased prevalence of rheumatoid arthritis in IgA-deficient persons this "reversed rheumatoid factor" (an IgG antibody to IgM proteins) in many IgA-deficient serums is noteworthy. This factor, however, will be missed in IgA-deficient serum if radial immunodiffusion tests with goat anti-IgA serum are used for the quantitation of IgA. The test will be misinterpreted and thought to show low IgA concentrations.
Doctor is struck off after third fitness to practise hearing
Authors: Clare Dyer
Journal: BMJ (2016)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Doctor is struck off after third fitness to practise hearing Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Cytogenetic Profile of Lymphoma of Follicle Mantle Lineage: Correlation With Clinicobiologic Features
Authors: Antonio Cuneo, Renato Bigoni, Gian Matteo Rigolin, Maria Grazia Roberti, Antonella Bardi, Nadia Piva, Raffaella Milani, Florencia Bullrich, Maria Luisa Veronese, Carlo Croce, Françoise Birg, Hartmut Döhner, Anne Hagemeijer, Gianluigi Castoldi
Journal: Blood (1999)
Genetics of Juvenile Diabetes Mellitus
Authors: Pablo Rubinstein, Nicole Suciu-Foca, John F. Nicholson
Journal: New England Journal of Medicine (1977)

We investigated the genetic predisposition to juvenile diabetes in the families of 31 index cases in relation to the inheritance of the HLA system. The diabetes-predisposing gene was found to be recessive because the diabetic sibs in index cases shared both their HLA genes with a significantly increased frequency. Penetrance was estimated at 50 per cent because half the HLA-identical sibs in index cases were diabetic. These conclusions fit with published observations that the risk to sibs of patients is about 100 per cent, when both parents are normal. In three informative cases of recombination within HLA the predisposing gene traveled with the HLA D segment of the recombinant haplotype. We prepared tables for the computation of risks to relatives, based on the hypothesis of recessivity, HLA linkage and 50 per cent penetrance.
An Experimental Program in Ambulatory Medical Care
Authors: James E. C. Walker, Benjamin J. Murawski, George W. Thorn
Journal: New England Journal of Medicine (1964)

IN October, 1961, the medical clinics of the Peter Bent Brigham Hospital undertook a program in ambulatory care that incorporated its specialty clinics into a form of group medical clinic. The major goals of the program are twofold: to provide a single physician responsible for each patient so as to strengthen the personalized elements in ambulatory care and to foster continuity; and to provide a broad educational experience in total patient care for the young physician.The following is a description of the experimental program and an analysis of its first two years' experience.BackgroundThe evolution of specialty clinics . . .
Implementation of standardized follow-up care significantly reduces peritonitis in children on chronic peritoneal dialysis
Authors: Alicia M. Neu, Troy Richardson, John Lawlor, Jayne Stuart, Jason Newland, Nancy McAfee, Bradley A. Warady, Joshua Zaristky, Susan Kieffner, Allison Redpath Mahon, Dawn Foster, Mahima Keswani, Nancy Majkowski, Richard Blaszak, Christine Blaszak, Michael Somers, Theresa Pak, Diego Aviles, Evie Jenkins, Rachel Lestz, Alice Sanchez, Cynthia Pan, Jackie Dake, Raymond Quigley, Bradley Warady, JoLyn Grimes, Kirtida Mistry, Jennifer Carver, Rene Van De Voorde, Ellen Irvin, Samhar Al-Akash, Britt Stone, Guillermo Hidalgo, Malinda Harrington, Alicia Neu, Barbara Case, Sushil Gupta, Andrea Baker, Jack Weaver, Annabelle Chua, Cynthia Wong, Brandy Begin, Isidro Salusky, Barbara Gales, Hiren Patel, Beth Smith, Mark Joseph, Deb Haskins, David Kenagy, Beth Vogt, Coral Hanevold, Nancy McAfee, Ann Beck, Meg Shea, Christine Sethna, Myung Cho, Sarah Scwartz, Helen Currier, Amy Skversky, Maureen Eisele, Madhura Pradhan, Christine Breen, Paul Brakeman, Lina Campopiano, Jennifer Jetton, Jennifer Ehrlich, Lawrence Shoemaker, Nancy Zacharek
Journal: Kidney International (2016)