tbuckley/cabot-search huggingface dataset:
Case 45-1969
Authors: Jeremiah G. Tilles, Benjamin Castleman
Journal: New England Journal of Medicine (1969)

Presentation of Case First admission. A twenty-five-year-old man was admitted to the hospital for renal transplantation.Eight years previously he had failed a medical examination for military induction because of proteinuria. Two years later the urine still gave positive tests for protein, and the serum nonprotein nitrogen was 54 mg per 100 ml. Hypertension was found when he was examined by a physician one year before admission. Fatigue became a prominent symptom six months later.There was no history of recurrent sore throats, rheumatic fever, arthritis, hearing loss, hematuria, dysuria or difficulty in voiding. The patient's mother had diabetes . . .
Identification of Risk Factors for Chemotherapy-Related 30-Day Readmissions
Authors: Jeremy Lund, Angela Pearson, Georgia Keriazes
Journal: Journal of the National Comprehensive Cancer Network (2015)

The goal of this study was to develop a method for practitioners to evaluate both quality of care delivered to patients receiving chemotherapy and illicit risk factors for 30-day chemotherapy-related readmissions (CRR).Midas+ DataVision Readmission Tool Pack (Version 2.x) was used to retrospectively identify patients who received inpatient chemotherapy from April 2010 through May 2013. The population was screened for unscheduled admissions within 30 days after discharge. A multidisciplinary team was used to attribute readmissions to chemotherapy administration. Demographic information and oncology-specific characteristics were collected. The CRR rate and relative risk for readmission were calculated for each characteristic.A baseline CRR rate of 11.1% was established. Risk factors associated with an increased risk for experiencing a CRR included age of 65 years or older, hematologic cancer diagnosis, first cycle chemotherapy, Medicare coverage, discharge to a skilled nursing facility, and anthracycline administration.A baseline CRR rate was established. Institution-specific 30-day CRR risk factors were elucidated. Modifiable risk factors included discharge to a skilled nursing facility and administration of an anthracycline. Further investigation for opportunities for quality improvement in these 2 risk factors is a topic for future research. Expanded research into chemotherapy-related toxicities requiring inpatient admission/readmission outside of clinical trials is warranted.
Critique on Vagotomy
Authors: William R. Moses
Journal: New England Journal of Medicine (1947)

AT LEAST fifty surgical procedures have been employed in the cure of chronic peptic ulcer since Doyen1 first suggested gastroenterostomy, nearly all of which have been based on arrest or neutralization of acid secretion. The operation of the hour is vagotomy, which owes its popularity to the imperfections of its immediate predecessor, subtotal gastrectomy.The criticisms of the end results of gastrectomy have been directed toward postoperative marginal and secondary ulcers, postoperative nutritional impairment, dyspepsia, diarrhea, defective fat absorption, secondary anemia, incomplete relief of pain, subsequent hemorrhages and "vagotonic symptoms." Postoperative ulceration is reported in 2 to 6 per cent . . .
Lipophilic nalmefene prodrugs to achieve a one-month sustained release
Authors: Tim Gaekens, Michel Guillaume, Herman Borghys, Loeckie L. De Zwart, Ronald de Vries, Roger C.A. Embrechts, An Vermeulen, Anton A.H.P. Megens, Josée E. Leysen, Piet Herdewijn, Pieter P. Annaert, John R. Atack
Journal: Journal of Controlled Release (2016)
Risk of Subsequent Disease among Day-Care Contacts of Patients with Systemic Hemophilus Influenzae Type B Disease
Authors: Trudy V. Murphy, Joe F. Clements, Jeri A. Breedlove, Eric J. Hansen, G. Burton Seibert
Journal: New England Journal of Medicine (1987)

There is controversy about whether to provide rifampin prophylaxis routinely to contacts in day-care facilities of a patient with a primary case of Hemophilus influenzae type b disease. We prospectively investigated primary cases of H. influenzae type b disease in day-care facilities in Dallas County, Texas, to determine the rate of subsequent disease among contacts. Ninety-one children with primary cases of H. influenzae type b disease who were attending day-care facilities were enrolled from October 1982 to October 1984. A total of 587 classroom contacts of these children under four years of age were not given rifampin. During 60 days of follow-up, there was one subsequent case in a classroom contact. Untreated children under two years of age who were directly exposed to a patient with a primary case were considered to be at highest risk of disease, but there were no subsequent cases in this group of 361 children. However, there were two cases in new enrollees who started attending day-care facilities during the 60-day follow-up period but who were not exposed to a patient with a primary case. At day-care centers in which there was a second case during the follow-up period, there was a high prevalence of colonization with H. influenzae type b in both patient and nonpatient groups of preschool children. These data indicate that the rate of subsequent disease in classroom contacts of patients in day-care facilities is lower than that reported in households (1 of 587 vs. 20 of 829, P = 0.001) and that this rate may be similar to the base rate of primary disease in day-care facilities. We conclude that rifampin prophylaxis may not be appropriate after the occurrence of a primary case of H. influenzae type b disease in a day-care facility in Dallas County.
A Radioassay for Serum Folate: Use of a Two-Phase Sequential-Incubation, Ligand-Binding System
Authors: Sheldon P. Rothenberg, Maria daCosta, Zoltan Rosenberg
Journal: New England Journal of Medicine (1972)

Abstract A folate binding-protein partially purified from milk was used as the binding ligand for a radioassay for serum folate. The procedure has a sensitivity of approximately 10 to 15 pg of N5-m...
Use of SPARC, EGFR, and VEGFR expression to predict response to nab-paclitaxel (nabP)/carboplatin (C)/bevacizumab (B) chemotherapy in triple-negative metastatic breast cancer (TNMBC).
Authors: E. P. Hamilton, G. G. Kimmick, N. Desai, S. Singh, J. O. Hopkins, P. K. Marcom, V. Chadaram, R. Welch, V. N. Trieu, K. L. Blackwell
Journal: Journal of Clinical Oncology (2010)

1109 Background: Improved therapies and predictive markers are needed in TNBC. B (bevacizumab) and C combinations are active in many solid tumors, including TNBC. SPARC is an albumin-binding protein secreted by tumors, a potential target of nabP. This study used enrollment metastatic biopsies (bxs) of TNMBC to 1) determine intratumor SPARC expression, 2) describe expression/activation of signaling pathways in TNMBC, and 3) correlate these expression patterns with response. Methods: first- and second-line TNMBC pts received nabP (100mg/m2) and C (AUC=2) d1,8,15, and B (10 mg/kg) d1,15 of a 28 d cycle. Formalin-fixed and fresh frozen metastatic bxs (first-line) were required. PFS, ORR, and CBR were determined. IHC was used to determine SPARC expression on tumor components and scored for stain intensity, % cells stained, and total score. A multiplexed COllaborative Proximity ImmunoAssay (COPIA: Prometheus) platform was used to determine comprehensive pathway protein (HER1, HER3, IGF1-R, c-KIT, c-MET, PI3K, VEGFR2, and AKT) expression/activation. The log-rank test was used to correlate protein expression with PFS. Results: At the time of analysis, the median PFS was 23 wks (n=27, 6-86 wks) without any significant grade 3/4 toxicities. 18 metastatic bxs were available (7 addl pending). ORR was 88% (3 CR, 19 PR, 3 SD, and 2 NE). Total EGFR was expressed in 10/18 (56%) metastatic bxs, but was activated in 3/18 (17%). PI3K and AKT were overexpressed in 10/18 (56%) bxs, and were co-expressed in 6/18 (33%) bxs. In 17 metastatic bxs, there was a longer PFS for higher SPARC score (33 wks vs. 22 wks, p=0.10), higher total EGFR expression (33 wks vs. 22 wks, p=0.14), and lower expression of VEGFR (33 wks vs. 18 wks, p=0.16). There were no correlations with additional markers and PFS. Conclusions: Nab-paclitaxel/carboplatin/bevacizumab offers a well tolerated and effective therapy for TNMBC. In this small sample of patients, overexpression of SPARC, total EGFR, and lower VEGFR2 levels may offer predictive value for response to triplet therapy in TNMBC. Real-time metastatic bxs may be influential in defining predictive markers of response for TNMBC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience, Prometheus Laboratories AstraZeneca, Genentech, Novartis Abraxis BioScience, Prometheus Laboratories Genentech Abraxis BioScience, Genentech
Ultra-deep and quantitative saliva proteome reveals dynamics of the oral microbiome
Authors: Niklas Grassl, Nils Alexander Kulak, Garwin Pichler, Philipp Emanuel Geyer, Jette Jung, Sören Schubert, Pavel Sinitcyn, Juergen Cox, Matthias Mann
Journal: Genome Medicine (2016)

The oral cavity is home to one of the most diverse microbial communities of the human body and a major entry portal for pathogens. Its homeostasis is maintained by saliva, which fulfills key functions including lubrication of food, pre-digestion, and bacterial defense. Consequently, disruptions in saliva secretion and changes in the oral microbiome contribute to conditions such as tooth decay and respiratory tract infections. Here we set out to quantitatively map the saliva proteome in great depth with a rapid and in-depth mass spectrometry-based proteomics workflow.We used recent improvements in mass spectrometry (MS)-based proteomics to develop a rapid workflow for mapping the saliva proteome quantitatively and at great depth. Standard clinical cotton swabs were used to collect saliva form eight healthy individuals at two different time points, allowing us to study inter-individual differences and interday changes of the saliva proteome. To accurately identify microbial proteins, we developed a method called "split by taxonomy id" that prevents peptides shared by humans and bacteria or between different bacterial phyla to contribute to protein identification.Microgram protein amounts retrieved from cotton swabs resulted in more than 3700 quantified human proteins in 100-min gradients or 5500 proteins after simple fractionation. Remarkably, our measurements also quantified more than 2000 microbial proteins from 50 bacterial genera. Co-analysis of the proteomics results with next-generation sequencing data from the Human Microbiome Project as well as a comparison to MALDI-TOF mass spectrometry on microbial cultures revealed strong agreement. The oral microbiome differs between individuals and changes drastically upon eating and tooth brushing.Rapid shotgun and robust technology can now simultaneously characterize the human and microbiome contributions to the proteome of a body fluid and is therefore a valuable complement to genomic studies. This opens new frontiers for the study of host-pathogen interactions and clinical saliva diagnostics.
Case 2-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Lot B. Page, Robert E. Scully
Journal: New England Journal of Medicine (1970)

Presentation of CaseA seventy-four-year-old man was admitted to the hospital because of uremia.He had been well until four months previously, when there was the onset of fatigue and pain in the lower portion of the back, for which his physician prescribed prednisolone. Because of persistent pain crutches were required. He continued to be fatigued and became lethargic and disinterested in his surroundings. Three months before admission and again one month before admission episodes of urinary hesitancy and dysuria occurred and were treated with antibiotics. Weekly examinations of the urine were allegedly negative. Ten days before entry nausea and . . .
Studies on the Preparation and Nature of a Gastric Secretagogue of Pancreatic Origin
Authors: Melvin P. Osborne, Louis N. Pernokas, Mayo Brown
Journal: New England Journal of Medicine (1963)

MANY functional interrelations between stomach and pancreas are familiar and have been studied in many species. The endocrine secretion of insulin by beta cells of the islands of Langerhans is well established, with importance in the control of blood sugar levels and carbohydrate metabolism. Gastric hypermotility and hypersecretion are known to occur during hypoglycemia and may be induced by insulin administration. This appears to be mediated through the central nervous system by the vagus innervation of the stomach; the Hollander test to determine the assumed completeness of surgical vagotomy is based upon this relation. Data observed in human patients appear . . .
S18 Ivacaftor treatment in preschool children with cystic fibrosis and a CFTR gating mutation: extended evaluation: Abstract S18 Table 1
Authors: JC Davies, S Cunningham, KW Southern, S Robertson, Y Green, J Cooke, M Higgins, M Rosenfeld
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, has demonstrated improved outcomes in patients aged ≥6 years with cystic fibrosis (CF) and a <i>CFTR</i> gating mutation. The phase 3, open-label, 24-week KIWI study assessed safety and pharmacokinetics of ivacaftor (50- or 75-mg granules twice daily [bid] for weight. <h3>Methods</h3> Patients who completed KIWI could enrol in KLIMB (an 84-week, open-label extension study). Dosing was the same as in KIWI for patients aged &lt;6 years; for patients aged ≥6 years, dosing was 150-mg tablets bid. <h3>Results</h3> KIWI enrolled 34 patients (mean age, 3.2 years); 33 enrolled in KLIMB. Cough was the most common AE in both KIWI (56%) and KLIMB (64%). Over the total 72-week treatment period, 8 patients had ALT or AST elevations of &gt;8× the upper limit of normal (ULN), 6 of whom had liver function tests (LFTs) &gt;2× ULN at pretreatment baseline. Six of the 8 patients with LFTs &gt;8× ULN had drug interruption; study drug was subsequently resumed. In total, 3 patients permanently discontinued study drug (elevated LFTs, n = 2; needle phobia, n = 1). Improvements in sweat chloride, faecal elastase-1, and immunoreactive trypsinogen were maintained over 72 weeks. Overall improvements from baseline in other exploratory outcome measures were also observed (Table 1). <h3>Conclusions</h3> A favourable overall safety profile was demonstrated with ivacaftor during extended follow-up in preschool patients with CF. Reported adverse events were consistent with the known safety profile of ivacaftor; additional monitoring of liver function may be required in this age group, particularly in patients with a history of elevated LFTs. Improvements in markers of pancreatic function and sweat chloride were sustained over the extended follow-up.
Pazopanib Versus Placebo in Women Without Progression After First-Line Chemotherapy for Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (Aeoc): Second Interim Overall Survival Analysis from the Ago-Ovar16 Trial
Authors: H. Nomura, L. Hanker, M. Fabbro, J. Rau, Y. Kim, J.A. Arranz Arija, M. Friedlander, G. Ferrandina, P. Vuylsteke, N. Colombo, S. Malander, B.J. Monk, E. Petru, P. Calvert, T. Herzog, C. Barrett, M. Jobanputra, Q. Wang, G. Elser, A. Du Bois
Journal: Annals of Oncology (2014)
Incidence of Spontaneous Neoplasms in F344 Rats Throughout the Natural Life-Span2
Authors: Bernard Sass, Louise S. Rabstein, Russell Madison, Robert M. Nims, Robert L. Peters, Gary J. Kelloff
Journal: JNCI Journal of the National Cancer Institute (1975)

The age-related incidence of spontaneously occurring neoplasms and degenerative diseases in the F344 inbred rat strain was established from the histologic examination of tissues from 160 male and 192 female rats kept throughout their natural life-span. The most common neoplasms were leukemias (25%), mammary tumors (females, 40.6%; males, 23.1 %), pituitary adenomas (females, 35.9%; males, 23.8%), and testicular interstitial cell tumors (males, 85%). Various less common neoplasms were observed: thyroid interstitial cell tumors, adrenocortical adenomas, carcinomas of the genitourinary tract, representative central nervous system tumors, pheochromocytomas, and tumors of mesodermal origin including mesotheliomas, myoblastomas, fibromas, and fibrosarcomas. Multiple tumor types were found in 176 of the rats; metastatic tumors were uncommon. Degenerative diseases including myocardial degeneration and nephrosis were often observed. The incidence rate of these neoplasms and degenerative diseases generally increased with advancing age of the animals.
Overexpression of an Osteogenic Morphogen in Fibrodysplasia Ossificans Progressiva
Authors: Adam B. Shafritz, Eileen M. Shore, Francis H. Gannon, Michael A. Zasloff, Rebecca Taub, Maximilian Muenke, Frederick S. Kaplan
Journal: New England Journal of Medicine (1996)

Fibrodysplasia ossificans progressiva is a heritable disorder of connective tissue characterized by congenital malformation of the great toes and postnatal formation of ectopic bone. Although the disorder was first described more than 300 years ago, the genetic defect and pathophysiology remain unknown. Bone morphogenetic proteins are potent bone-inducing morphogens that participate in the developmental organization of the skeleton, and increased production of one or more of these proteins has been proposed as the cause of fibrodysplasia ossificans progressiva.
Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies
Authors: Emily Bartsch, Karyn E Medcalf, Alison L Park, Joel G Ray
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks' gestation to estimate a woman's risk of pre-eclampsia. <b>Design</b>&nbsp;Systematic review and meta-analysis of cohort studies. <b>Data sources</b>&nbsp;PubMed and Embase databases, 2000-15. <b>Eligibility criteria for selecting studies</b>&nbsp;Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks' gestation. <b>Data extraction</b>&nbsp;Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. <b>Results</b>&nbsp;There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) &gt;30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. <b>Conclusions</b>&nbsp;There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at "high risk" of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.
Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial
Authors: Ian Roberts, David Yates, Peter Sandercock, Barbara Farrell, Jonathan Wasserberg, Gabrielle Lomas, Rowland Cottingham, Petr Svoboda, Nigel Brayley, Guy Mazairac, Véronique Laloë, Angeles Muñoz-Sánchez, Miguel Arango, Bennie Hartzenberg, Hussein Khamis, Surakrant Yutthakasemsunt, Edward Komolafe, Fatos Olldashi, Yadram Yadav, Francisco Murillo-Cabezas, Haleema Shakur, Phil Edwards
Journal: The Lancet (2004)
Systems pathology for building predictive models: The androgen receptor as a prototype biomarker in prostate cancer progression and targeted therapeutic response assessment
Authors: M. J. Donovan, H. Scher, P. Scardino, A. Kotsianti, C. Cordon-Cardo
Journal: Journal of Clinical Oncology (2006)

4504 Background: A functional androgen receptor (AR) signaling axis plays a critical role in prostate cancer (PCA) development and progression across the clinical spectrum of the illness. Following diagnosis, most prostate cancers respond to treatments that block circulating androgen levels or block AR action. The measurement of AR levels in tumor tissue samples has the potential to provide prognostic information, to treatment selection, and a measure of the pharmacodynamic effect of a therapeutic agent(s) designed to reduce AR levels or block AR action. Existing methods to assess AR antigen levels in tissue are subjective, we have developed a systems pathology strategy for interrogating biomarker assessment in a predictive model by integrating clinical data with histological and quantitative antigen profiles. Methods: Tissue microarrays from 366 MSKCC patients were stained with H&amp;E, images captured, analyzed and quantitative cellular features produced. Immunohistochemistry (IHC) was performed for AR and a staining index generated. A multiplex immunofluorescent (IF) assay using DAPI, CK18 and AR was performed on a subset of patients. IF mages were acquired and specific IF scripts were used to generate quantitative features of AR which were compared with AR IHC data. Results: Androgen Receptor levels by IHC in PCA demonstrated that a high-level of expression was associated with a greater risk of PSA-relapse within 5 years. (P &lt; 0.0001; cut point 100). The correlation of AR IF with AR IHC established that all derived AR-IF measurements were statistically associated with the AR-IHC data. Furthermore, in a very preliminary model using machine learning and feature selection to predict PSA recurrence, 1AR-IF feature (epithelial and stromal AR) along with 2 clinical variables was selected with a concordance index of 0.80. Conclusion: AR levels in newly diagnosed localized prostate cancer are associated with clinical outcome. The levels can be assessed accurately and in a standardized manner using quantitative multiplex antigen methods. Such approaches are critical for evaluating biomarkers, especially when determining therapeutic response and clinical endpoints. [Table: see text]
Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation
Authors: Ming-Yi Shen, Fang-Yu Chen, Jing-Fang Hsu, Ru-Huei Fu, Chia-Ming Chang, Chiz-Tzung Chang, Chung-Hsiang Liu, Jia-Rong Wu, An-Sheng Lee, Hua-Chen Chan, Joen-Rong Sheu, Shinn-Zong Lin, Woei-Cherng Shyu, Tatsuya Sawamura, Kuan-Cheng Chang, Chung Y. Hsu, Chu-Huang Chen
Journal: Blood (2015)
Augmentation of the Plasma Nor-Epinephrine Response to Exercise in Patients with Congestive Heart Failure
Authors: Charles A. Chidsey, Donald C. Harrison, Eugene Braunwald
Journal: New England Journal of Medicine (1962)

THE manner in which the cardiovascular system responds to the increased metabolic demands of muscular exercise is of considerable interest to the clinician and physiologist. It has been suggested that the sympathetic nervous system plays an important part in mediating this response in normal man.1 2 3 4 5 In patients in whom the cardiac reserve is diminished, the normal increase of cardiac output during exercise is attenuated, or even abolished.6 , 7 It is not known to what extent the sympathetic nervous system is called into play under these circumstances. Diminished activity of this important reserve mechanism could be a factor in the abnormal cardiac . . .