tbuckley/cabot-search huggingface dataset:
Abstract OT2-3-07: A randomized, phase 2 study of the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) in combination with temozolomide (TMZ) or in combination with carboplatin (C) and paclitaxel (P) versus placebo plus C/P in subjects with <i>BRCA1</i> or <i>BRACA2</i> mutation and metastatic breast cancer
Authors: SJ Isakoff, S Pulhalla, SP Shepherd, N Falotico, B Kaufman, M Friedlander, M Robson, S Domchek, J Garber, E McKeegan, B Chyla, J Qian, VL Giranda
Journal: Cancer Research (2012)

Abstract Background: Veliparib is a potent, oral PARP inhibitor that inhibits DNA repair, primarily through single strand break repair. BRCA1/2 mutated tumors are defective in homologous recombination, leading to more error prone mechanisms of DNA repair and increased sensitivity to PARP inhibition. Veliparib and TMZ recently demonstrated promising activity in BRCA1/2 mutation carriers, and veliparib and C/P is being evaluated in a CTEP Phase 1 study. This Phase 2 multinational study will evaluate veliparib in combination with TMZ and in combination with C/P compared to an active, placebo-controlled arm of C/P in subjects with BRCA1 or BRCA2 mutation and metastatic breast cancer. Methods: Approximately 240 subjects will be randomized in a 1:1:1 ratio to: 1) Veliparib 40 mg BID D1-7 + TMZ (150–200 mg/m2 QD D1-5) of every 28 day cycle; or 2) Veliparib 120 mg BID D1-7 + C (AUC 6, D3) and P (175 mg/m2, D3) of every 21 day cycle or 3) placebo BID D1-7 + C/P. Key eligibility includes known deleterious BRCA1/2 mutation, ≤1 prior chemotherapy for metastatic disease, and no prior platinum agent. Randomization will be stratified by hormone receptor positive versus negative, prior vs. no prior cytotoxic therapy, and ECOG 0–1 vs 2. The primary objective is progression-free survival (PFS) using RECIST 1.1. Secondary objectives include overall survival, objective response rate, duration of response and safety/tolerability. Optional paired tissue biopsies will be obtained at baseline and at progression to evaluate markers of response and resistance. Additional correlatives for response include assessment of peripheral blood, CTCs, and archived tissue for markers of disease status, gene methylation and mutational status, and tumor-specific alteration of cellular proteins/peptides and/or nucleic acids. Using the log-rank test for PFS, with 150 PFS events the study will have ≥ 80% power at 2-sided α level of 0.05 to detect a statistically significant treatment effect assuming a true hazard ratio of 0.58 favoring the 2 treatment groups containing veliparib. As of June 11, 2012, 5 subjects have been enrolled. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr OT2-3-07.
Detection of the His1069Gln Mutation in Wilson Disease by Rapid Polymerase Chain Reaction
Authors: Theresia Maier-Dobersberger
Journal: Annals of Internal Medicine (1997)

Most known mutations in the gene associated with Wilson disease are rare. Only the His1069Gln mutation is found often in patients of Northern or Eastern European origin.To examine the frequency of the His1069Gln mutation in Austrian patients with Wilson disease and their families by using a new, rapid polymerase chain reaction (PCR) test.Cross-sectional study.University medical center.83 patients from 72 families and 98 relatives of 11 homozygous index patients.Results of a semi-nested PCR-based assay to detect the His1069Gln mutation in Wilson disease, clinical symptoms, and liver histologic findings.20 patients, including 5 siblings, were homozygous for the His1069Gln mutation. Thirty-three patients, including 4 siblings, were compound heterozygotes. The mutation was not detected in 30 patients, including 2 siblings. Homozygotes were older at onset of symptoms (mean age, 24 +/- 6 years) than compound heterozygotes (17 +/- 6 years [95% CI, 3.3 to 10.7 years]; P = 0.0135) and patients with other mutations (18 +/- 8 years [CI, 1.8 to 10.2 years]; P = 0.117). Homozygotes were more often female (73.3%) than were compound heterozygotes (48% [CI, 0.94% to 2.46%]) and patients with other mutations (50% [CI, 0.91% to 2.37%]) (P = 0.05). Four of 98 asymptomatic relatives of 11 homozygous index patients were also homozygotes. Heterozygosity was confirmed in 46 relatives (19 parents, 11 children, and 16 distant relatives).The His1069Gln mutation was detected in 61% of Austrian patients with Wilson disease. Polymerase chain reaction may be useful for diagnosis and screening of family members of homozygous index patients, even if first-degree relatives are not available for examination.
Partial Biliary Obstruction Due to Adenomyoma of the Terminal Common Bile Duct
Authors: LAWRENCE A. GILBERT, YUNG S. PARK, KHAIROON M. ALLY
Journal: Clinical Nuclear Medicine (1986)

A patient with “histiocytic lymphoma” with abnormal liver function studies underwent hepatobiliary scintigraphy. The study was consistent with partial distal common bile duct obstruction. Subsequently, the patient died. Autopsy revealed an adenomyoma of the distal common bile duct with a markedly narrowed lumen.
Annexin II and Bleeding in Acute Promyelocytic Leukemia
Authors: Jill S. Menell, Gabriela M. Cesarman, Andrew T. Jacovina, Mary Ann McLaughlin, Emil A. Lev, Katherine A. Hajjar
Journal: New England Journal of Medicine (1999)

Acute promyelocytic leukemia (APL) is associated with a hemorrhagic disorder of unknown cause that responds to treatment with all-trans-retinoic acid.
A NEW STETHOSCOPE.
Authors: W. H. TenBroeck
Journal: JAMA (1897)

Paris, Ill., Jan. 25, 1897. <h3>To the Editor:</h3> —Being unable to find a stethoscope that was efficient, simple and portable, I devised the one here represented, compared it with Camman's different styles, the Dennison and the phonendoscope, and found it the best instrument for general use. It is easily carried in the pocket, in a tight box to exclude dust, etc., which is much in its favor, as I know from having carried a cumbersome stethoscope for nearly twenty years. My last purchase was a phonendoscope, which transmits sounds perfectly, but does not locate them satisfactorily, besides being uncomfortable to the patient and too heavy to carry in the pocket. The above instrument is made by Geo. Tiemann &amp; Co., New York city. If the ear pieces do not fit, they will either admit external sounds or cause roaring. Respectfully,
Biblical Reason for Forbidding Use of Milk And Meat
Authors: Max M. Stern
Journal: JAMA (1961)

<h3>To the Editor:—</h3> I am astonished to read inThe Journal, Jan. 14, page 163, Dr. Morris Chamurich's letter about the biblical reason for forbidding the use of milk and meat, which he explains on grounds of their being infected with<i>Brucella</i>. In reality there is no biblical prohibition of milk and meat. What is forbidden in the Bible is the<i>cooking together</i>of milk and meat: "Thou shalt not cook the kid in the milk of its mother." This has been extended in talmudic times to the prohibition of<i>eating</i>milk and meat<i>together</i>. If this prohibition had been for hygienic reasons, the eating of the goat and the drinking of goat's milk would have been included in the list of prohibited food. The meaning has, like all Jewish biblical dietetic laws, nothing to do with hygiene—as little as, e.g., the prohibition of eating pork. This prohibition was a
RECURRENCES IN CANCERS OF THE BREAST
Authors: JOHN E. SUMMERS
Journal: JAMA (1923)

In the light of today it would be supererogation on my part to recapitulate the end-results of the operative treatment of cancer of the breast as reported by many clinics and individual operators throughout the world. The results in the main are about the same, and the technic employed in general varies so little that claims of superiority in end-results on that score are hardly worthy of serious consideration. A clearly operable cancer of the breast which recurs locally indicates that either the technic was incomplete or else that its lymphatic extension had passed beyond the limits of the field of operation, however well the operation was performed. Again, in an instance of metastatic recurrence, if a pathologic study of the specimen removed fails to detect cancer elements beyond the border of the parts removed, then metastasis had already taken place before the operation was performed. The most important thing
Trends in Prostatic Surgery-Reply
Authors: J. L. McCormack
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Additional tables itemizing the statistical data were omitted from the final form of this paper. Nevertheless, the total numbers of patients undergoing open and closed procedures may be computed from the data published, since the total number of patients and the mortality rates for each classification were given. Dr. Glucksman could probably test these data by the chi-square method. The second point, concerning the age distribution and coexisting medical disease between the open and closed groups, is well taken. As stated in the communication, a variety of urologic surgeons with different backgrounds of training were involved. The authors do not subscribe to the concept that transurethral resections are less hazardous than open procedures but readily concede that this attitude held by one or more of our colleagues may exist to color the overall mortality rates.
A Method for Endoscopic Inspection of the Bursa Omentalis
Authors: S.A. Charukhchyan
Journal: Endoscopy (1986)

Hitherto there have been no methods of direct inspection of all the organs and tissues composing the bursa omentalis. A method for the endoscopic inspection of the bursa omentalis that is highly informative and applicable in the great majority of cases has been developed on 22 cadavers, and used on 6 patients. The technique is described and its possibilities are discussed.
Insulin regulation of rat growth hormone gene transcription.
Authors: S Yamashita, S Melmed
Journal: Journal of Clinical Investigation (1986)

We have previously shown that insulin suppresses growth hormone (GH) messenger (m) RNA levels in rat pituitary cells. To further delineate the molecular mechanism of insulin action, the effect of insulin treatment on GH gene transcription rates was examined in GH3 pituitary cells grown in serum-free defined medium. A transcriptional run-off assay was performed when intact isolated nuclei were allowed to continue RNA synthesis in an in vitro reaction. Specific incorporation of [32P]GTP into RNA was quantified by hybridization to rat GH complementary (c) DNA. Hybridization efficiency was measured with an internal [3H]cRNA standard and ranged from 30 to 48%. Alpha-amanitin (1 microgram/ml) inhibited total transcription, and excess unlabeled rat pituitary mRNA (250 ng) competitively inhibited GH mRNA hybridization by greater than 80%. Insulin (0.7 nM) inhibited new GH mRNA synthesis, and maximal inhibition (30% of control) was observed with 7 nM insulin after 4 h treatment. The inhibitory effects of insulin on new GH mRNA synthesis were abolished by both insulin-receptor-antiserum and by guinea-pig anti-insulin serum. The results show that insulin exerts a rapid suppression of new GH mRNA synthesis. These data provide evidence for the direct transcriptional regulation of the GH gene by insulin.
Edema: Mechanisms and Management. A Hahnemann Symposium on Salt and Water Retention
Authors: Roderick Darby
Journal: JAMA (1960)

This symposium is a comprehensive review of the mechanisms and management of edema by over 100 investigators and clinicians. Since edema is not a problem peculiar to any one specialty in medicine, the authors comprise internists, pediatricians, surgeons, obstetricians, pharmacologists, physiologists, and biochemists. The symposium is composed of three main parts. The initial chapters deal with the basic physiology of fluid and electrolyte balance as it pertains to the mechanisms of edema. The complex interrelationships of the kidneys, adrenals, liver, lymphatics, and the cardiovascular system are discussed at length. This is followed by several chapters on the pharmacological and clinical applications of the diuretic agents. The mechanisms, uses, and efficacy of the xanthine diuretics, mercurial diuretics, triazine compounds, and the carbonic anhydrase inhibitors are discussed. Considerable attention is centered on the thiazide derivatives. The diuretic effects of the digitalis glycosides and adrenal steroids are mentioned as well as the new
Mercy Killing-Reply
Authors: James S. Goodwin
Journal: JAMA (1991)

In Reply.—  Dr Tauber extends my arguments against euthanasia of incompetent people to encompass euthanasia of competent people, and then disagrees with the result. So do I. I agree with both Drs Tauber and Kane that the appropriate use of advance directives can considerably lessen the uncertainty and guilt encountered by families facing treatment decisions for an incompetent relative. That uncertainty is poignantly illustrated in the letter from Dr Morgan. Finally, I strongly disagree with Dr Kane's assertion that all surrogate decisions are selfish. Pellegrino and Thomasma, 1 among others, have argued that the concept of beneficence is a better way to view the physician-patient relationship than is the physician praternalism—patient autonomy dialectic. Clearly, most surrogate decisions are made for the patient's good.
BLEEDING EVENTS AFTER TRANSCATHETER AORTIC VALVE IMPLANTATION: USEFULNESS OF BASELINE ACTIVATED CLOTTING TIME IN GUIDING THE ANTITHROMBOTIC REGIMEN DURING TRANSCATHETER AORTIC VALVE IMPLANTATION PROCEDURES
Authors: Chiara Bernelli, Alaide Chieffo, Matteo Montorfano, Francesco Maisano, Azeem Latib, Mauro Carlino, Filippo Figini, Francesco Giannini, Gill Louise Buchanan, Remo Daniel Covello, Chiara Gerli, Franco Annalisa, Eustachio Agricola, Giovanni La Canna, Ottavio Alfieri, Antonio Colombo
Journal: Journal of the American College of Cardiology (2013)
OBSTRUCTION OF THE BOWELS.
Authors: T. F. PREWITT
Journal: JAMA (1898)

" Obstruction of the bowels" is a technical phrase which implies a mechanical obstacle to the onflow of the intestinal contents. Its causes are various and the obstruction may be complete or partial, acute or chronic. It may occur at any portion of the intestinal tract from the duodenum to the rectum. It may be due to conditions that are congenital or may be acquired. But whatever may be the character of the obstruction the one striking fact dominates all considerations relating to treatment—it is a mechanical obstacle. A simple reference to the schedule of causes, revealed by postmortems, establishes this fact and demonstrates as well the utter uselessness of medical measures. It is impossible here to more than outline the symptoms, diagnosis and treatment of obstruction of the bowels, acute and chronic. It is neessary to deal with these two groups separately. In the classification of intestinal obstruction it is
Non-invasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis
Authors: J. V Lightowler
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives:</b> To determine the effectiveness of non-invasive positive pressure ventilation (NPPV) in the management of respiratory failure secondary to acute exacerbation of chronic obstructive pulmonary disease. <b>Design:</b> Systematic review of randomised controlled trials that compared NPPV and usual medical care with usual medical care alone in patients admitted to hospital with respiratory failure resulting from an exacerbation of chronic obstructive pulmonary disease and with PaCO<sub>2</sub> &gt;6 kPa. <b>Results:</b> The eight studies included in the review showed that, compared with usual care alone, NPPV as an adjunct to usual care was associated with a lower mortality (relative risk 0.41 (95% confidence interval 0.26 to 0.64)), a lower need for intubation (relative risk 0.42 (0.31 to 0.59)), lower likelihood of treatment failure (relative risk 0.51 (0.38 to 0.67)), and greater improvements at 1 hour in pH (weighted mean difference 0.03 (0.02 to 0.04)), PaCO<sub>2</sub> (weighted mean difference −0.40 kPa (−0.78 to −0.03)), and respiratory rate (weighted mean difference −3.08 breaths per minute (−4.26 to −1.89)). NPPV resulted in fewer complications associated with treatment (relative risk 0.32 (0.18 to 0.56)) and shorter duration of stay in hospital (weighted mean difference −3.24 days (−4.42 to −2.06)). <b>Conclusions:</b> NPPV should be the first line intervention in addition to usual medical care to manage respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease in all suitable patients. NPPV should be tried early in the course of respiratory failure and before severe acidosis, to reduce mortality, avoid endotracheal intubation, and decrease treatment failure. <h3>What is already known on this topic</h3> Prospective studies, especially the larger studies, have shown that non-invasive positive pressure ventilation (NPPV) reduces the need for intubation, improves survival, and reduces complications in patients with respiratory failure resulting from exacerbation of chronic obstructive pulmonary disease (COPD) A previous meta-analysis showed NPPV to be an effective intervention, including for acute exacerbations of COPD, but some studies in this meta-analysis contained mixed groups of patients and were not of good quality <h3>What this study adds</h3> Evidence from good quality, randomised controlled trials shows that NPPV is an effective treatment for acute exacerbations of COPD NPPV should be considered early in the course of respiratory failure and before severe acidosis ensues, to avoid the need for endotracheal intubation and reduce mortality in patients with COPD
Arrhythmic and Antiarrhythmic Effects of Sodium, Potassium, and Calcium Salts and of Glucose Injected into Coronary Arteries of Infarcted and Normal Hearts
Authors: A. SIDNEY HARRIS, LOUIS A. TOTH, TAN ENG HOEY, Dunca D. Burford, Richard A. Liptak, Djamadina Anwar
Journal: Circulation Research (1958)

Substances that have not exhibited properties as excitants of ectopic activity by intracoronary injection into normal hearts often produce rapid ectopic activity and sometimes ventricular fibrillation upon slow injection through the vascular bed of an infarcted area, particularly upon the first one or two injections. Sodium lactate has reduced and stopped ectopic activity for brief periods. Excesses of both potassium and calcium have increased ectopic activity in infarction and produced it in normal hearts. No antagonism between these two ions, with respect to ectopic activity, has been demonstrated.
Protein Microarray: IgE-Profiling Of Brazilians With Atopic Dermatitis
Authors: Lucila Camargo Lopes de Oliveira, Roberta Faria Camilo-Araújo, Isabel Rugue Genov, Renata R. Cocco, Marcia Mallozi, Nelson A. Rosario, Dirceu Sole
Journal: Journal of Allergy and Clinical Immunology (2014)
Age-associated changes in left atrial appendage function: a population-based transesophageal echocardiographic study
Authors: Y. Agmon, B.K. Khandheria, L. Meissner, J.P. Whisnant, J.D. Sicks, W.M. O'Fallon, J.L. Covalt, J.B. Seward
Journal: Journal of the American College of Cardiology (1998)
The Canadian Health Care System
Authors: A L Linton
Journal: New England Journal of Medicine (1990)

Canada is perceived to have one of the best health care systems in the developed world, publicly funded and providing universal coverage. It has avoided the direct governmental controls of Britain's National Health Service and the increasingly close monitoring of medical decisions by third-party payers in the United States. With U.S. health care costs exceeding 11 percent of the gross national product and continuing to rise,1 it is no surprise that Americans are increasingly interested in the apparent structural efficiency of Canadian health care.2 This interest is driven by concern over 37 million citizens without health insurance and by the . . .
Roentgenologic Diagnosis: A Complement in Radiology to the Beeson and McDermott Textbook of Medicine
Authors: E. James Potchen
Journal: JAMA (1968)

Classic anatomic roentgenology correlates recognizable patterns with specific disease entities. These two volumes contain a comprehensive atlas of disease-related radiographic plates to be used as a companion to the Beeson and McDermott<i>Textbook of Medicine</i>. The reproductions are excellent. It is unfortunate that the writing does not equal the radiographs. There are many errors in content and concept evident in the short essays adjacent to each radiograph. For example, the authors claim that the lung parenchyma becomes involved in one third of patients with Hodgkin's disease, which is not consistent with current experience (eg, Kaplan). The authors emphasize pathologic anatomy in a classical format, and one is struck by the lack of physiologic and kinetic considerations evident in modern radiology. Therefore, in this reviewer's opinion, the book will have limited value for medical students, who would better obtain a firm grounding in modern diagnostic radiology and its potential for pathophysiologic
Deterioration of the NHS
Authors: J D Ward, C Peat, J Revill
Journal: BMJ (1994)

EDITOR, - We have recently expressed our concern in the national press about the deteriorating state of the health service.*RF 1-4* We have highlighted several important issues.

Firstly, appreciable problems in the handling of patients with acute medical problems, due to lack of beds and the diminishing number of hours worked by doctors, have led to long delays in accident and emergency departments and admissions wards and dangerous clinical care. This has been aggravated …
Immunoglobulins in Mink Ranchers Associated With Aleutian Disease
Authors: Ralph C. Williams
Journal: JAMA (1965)

Aleutian disease (AD) is characterized in mink by marked hypergammaglobulinemia; plasma-cell infiltration of liver, kidneys, and lymph nodes; and terminal bleeding tendency. A survey of fur-farm associates was prompted by a report of a fatal illness, similar in some clinical and pathological aspects to AD, in a mink rancher. Particular attention was directed toward quantitative measurement of immunoglobulins IgG, IgA, and IgM as an index of possible subclinical AD infection. No distinct immunoglobulin abnormalities among the fur-farm associates were uncovered when compared to controls matched for age and sex. Since the presumed infectious agent has not yet been isolated or characterized, direct serologic testing for specific AD antibody among mink handlers cannot yet be evaluated.
Evaluation of Recent Results
Authors: Michael B. Shimkin
Journal: JAMA (1973)

In 1963, Easson and Russell<sup>27</sup>reported that 13% of 822 patients with Hodgkin's disease were alive at 15 years and were presumably cured by radiotherapy. Curative therapy became the primary clinical objective in Hodgkin's disease, replacing symptomatic amelioration. Improved clinical staging and histological classification facilitated therapeutic management. In a report by Peters et al,<sup>28</sup>of 1,131 patients treated with radiotherapy from 1931 to 1969, the five-year survival rate was 43%. During the period from 1965 to 1969, with the completion of five years of observation of 64 patients, the survival was 59%; it is stated that 40% of these patients were in stages I and II of the disease. The radiotherapy center at Stanford<sup>29</sup>reports 275 patients with Hodgkin's disease, of whom 54 have completed five years of observation. The five-year survival was 73%; however, 80% of the patients were in stages I and II of the