tbuckley/cabot-search huggingface dataset:
ATCT-27NRG ONCOLOGY/RTOG 0929: A RANDOMIZED PHASE I/II STUDY OF ABT-888IN COMBINATION WITH TEMOZOLOMIDE IN RECURRENT TEMOZOLOMIDE RESISTANT GLIOBLASTOMA
Authors: H. Ian Robins, Peixin Zhang, Mark Gilbert, Arnab Chakravarti, John deGroot, Sean Grimm, Fen Wang, Frank Lieberman, Andra Krauze, Anand Sharma, Nimish Mohile, Andrew Kee, Howard Colman, Robert Cavaliere, Santosh Kesari, Steven Chmura, Minesh Mehta
Journal: Neuro-Oncology (2015)

INTRODUCTION: This study tested the hypothesis that ABT-888 (veliparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, can modulate temozolomide (TMZ) resistance in recurrent, TMZ-refractory glioblastoma (GBM) patients. METHODS: The combination regimen (TMZ/ABT-888) was tested using 2 randomized schedules (5 or 21 days of a 28 day cycle). Two cohorts were studied: bevacizumab naive (BEV-N), and BEV refractory (BEV-R). Six-month progression free survival (PFS6) was the primary endpoint, with hypothesized rates of 30% for BEV-N and 15% for BEV-R; using one-sample binomial tests; alpha = 0.10 and 90% power. Arm 1 combined 40 mg BID ABT-888 with TMZ using the 21/ 28 day schedule at 75 mg/m2. Arm 2 combined ABT-888 (40 mg BID) with TMZ using the 5/ 28 day TMZ at 150-200 mg/m2. RESULTS: Of 151 BEV-N and 74 BEV-R patients, 10 were ineligible. The incidence rate of grade 3/4 myelosuppression was 20.0%. For both arms, PFS6 for BEV-N was 17.0%; 4.4% for BEV-R. Median overall survival (OS) was 10.3 months (95% CI, 8.4-12.0) for BEV-N and 4.7months (95%CI, 3.5-5.6) for BEV-R. The median PFS was essentially the same for both arms and both cohorts at ∼2.0M (95% CI, 1.9-2.1). CONCLUSIONS: The combination of TMZ and ABT-888 did not significantly improve PFS6 for either BEV-N or BEV-R patients with recurrent GBM who had been previously treated with TMZ. For both groups of patients, the objective response rate was low, and did not differ by treatment arm, and the OS and PFS were similar for both treatment arms. Although MGMT status was not included for eligibility and therefore not analyzed, the low response rates, low PFS and low OS suggest that the likelihood of a clinically meaningful benefit for an MGMT-defined subset is remote. Support: Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, and UG1CA189867 from the National Cancer Institute (NCI) and AbbVie.
Judging the Past: How History Should Inform Bioethics
Authors: Barron H. Lerner, Arthur L. Caplan
Journal: Annals of Internal Medicine (2016)

Bioethics has become a common course of study in medical schools, other health professional schools, and graduate and undergraduate programs. An analysis of past ethical scandals, as well as the bioethics apparatus that emerged in response to them, is often central to the discussion of bioethical questions. This historical perspective on bioethics is invaluable and demonstrates how, for example, the infamous Tuskegee syphilis study was inherently racist and how other experiments exploited mentally disabled and other disadvantaged persons. However, such instruction can resemble so-called Whig history, in which a supposedly more enlightened mindset is seen as having replaced the “bad old days” of physicians behaving immorally. Bioethical discourse—both in the classroom and in practice—should be accompanied by efforts to historicize but not minimize past ethical transgressions. That is, bioethics needs to emphasize why and how such events occurred rather than merely condemning them with an air of moral superiority. Such instruction can reveal the complicated historical circumstances that led physician-researchers (some of whom were actually quite progressive in their thinking) to embark on projects that seem so unethical in hindsight. Such an approach is not meant to exonerate past transgressions but rather to explain them. In this manner, students and practitioners of bioethics can better appreciate how modern health professionals may be susceptible to the same types of pressures, misguided thinking, and conflicts of interest that sometimes led their predecessors astray.
Case report of phenothiazine-induced torsade de pointes
Authors: W H Wilson, S J Weiler
Journal: American Journal of Psychiatry (1984)

A patient with schizophrenia developed torsade de pointes, a life-threatening cardiac arrhythmia, due to administration of phenothiazines. An intravenous infusion of isoproterenol improved the symptoms. The etiology and treatment of the syndrome are discussed.
John Shaw Billings
Authors: J. Fraser Muirhead
Journal: New England Journal of Medicine (1963)

THE Civil War Centennial, the fiftieth anniversary of the opening of the New York Public Library's main building and the dedication of the new home of the National Library of Medicine with its electronic computers occurred in 1961. Each of these events recalled John Shaw Billings (Fig. 1).Billings was born on April 12, 1838, in southern Indiana. Despite his poor backwoods origin, he early developed a love of books. His schooling was accomplished despite hardships that may be estimated by his later remark, quoted by Silas Weir Mitchell, that he never fully recovered from living one winter on 75 . . .
Obtaining Access to Data from Government-Sponsored Medical Research
Authors: Bryan Jay Yolles, Joseph C. Connors, Seymour Grufferman
Journal: New England Journal of Medicine (1986)

Increasingly, the federal government sponsors medical research to resolve major public health issues. Government sponsorship of such research can take many forms, such as grants to university departments or individual investigators, contracts with private research firms, or direct funding of research conducted by its own employees. Access to data supporting the results of such research may become extremely important to many different parties, often at odds with one another. Public health and regulatory agencies, as well as product-liability litigants and public interest groups, often need more data than are provided in published research papers in order to execute their responsibilities . . .
Case 27-2010
Authors: Eyal C. Attar, Robert P. Hasserjian
Journal: New England Journal of Medicine (2010)

A 73-year-old woman was seen in the cancer center at this hospital for management of a myelodysplastic syndrome. She had had anemia for 2 years, and a diagnosis of a myelodysplastic syndrome with isolated del(5q) had been made 1 year earlier. She required red-cell transfusions every 2 months to maintain a hematocrit of 30%; she did not have recurrent infections or bleeding. A management decision was made.
Does joint custody work? A first look at outcome data of relitigation
Authors: F W Ilfeld, H Z Ilfeld, J R Alexander
Journal: American Journal of Psychiatry (1982)

Joint custody, with both divorced parents sharing childrearing functions, is a recent and controversial phenomenon. To the authors' knowledge there have been no published quantitative outcome studies establishing its efficacy. The authors present data on 414 consecutive custody cases in a Los Angeles court over a 2-year period, comparing relitigation rates (indicative of postdivorce parental conflict) of exclusive and joint custody. In those cases which were returns to court, the proportion of relitigation for joint custody families was one-half that of exclusive custody families, suggesting that joint custody is a more beneficial arrangement in terms of reduced parental conflict.
Pindolol: A New β-Adrenoceptor Antagonist with Partial Agonist Activity
Authors: Jan Koch-Weser, William H. Frishman
Journal: New England Journal of Medicine (1983)

Pindolol (Visken) is a β-adrenoceptor antagonist that was released in November 1982 for clinical use in the United States (Fig. 1). After propranolol, metoprolol, nadolol, atenolol, and timolol, it is the sixth orally active β-blocker to be approved by the Food and Drug Administration for the treatment of systemic hypertension. The drug has been marketed widely outside the United States since 1969 for hypertension, angina pectoris, and arrhythmias.Despite the therapeutic similarity of the β-blocking drugs, some differences in their pharmacodynamic and pharmacokinetic properties may be clinically important.1 The β-blockers are usually classified according to the presence or absence of . . .
Laboratory and Clinical Experience with Carbomycin
Authors: William L. Hewitt, J. P. Wood
Journal: New England Journal of Medicine (1953)

CARBOMYCIN is a new antibiotic substance produced by a soil actinomycete, Streptomyces halstedii. The isolation, purification and characterization of its physical and chemical properties have been accomplished by the workers from the Pfizer Research Laboratories.1 It is a crystalline, monobasic substance containing carbon, hydrogen and nitrogen with a molecular weight of about 860. The free base is only slightly water soluble, but dissolves readily in organic solvents. Acid salts such as the hydrochloride, phosphate or sulfate are prepared readily and are water soluble. Low degrees of both acute and chronic toxicity were noted for animals, including dogs, after both . . .
THE LANGUAGE OF HEALTH CARE: Cycling is not more dangerous than walking
Authors: M. J Wardlaw
Journal: Journal of the Royal Society of Medicine (2006)

Sonkin et al.1 focused on fatality rates per mile travelled in comparing risk to children walking, cycling and being driven. Fatality rates per mile travelled for children aged 0-14 years were 30 times greater for pedestrians and 50 times greater for cyclists than for those carried in cars. Walking and cycling appear very dangerous, cycling especially so, whereas being driven is safe.

Let us take the 0.55 deaths per 10 million miles for child cyclists: what kind of a risk is this in everyday terms? Suppose an individual cycled 100 000 miles in their life, all at the fatality rate of a child cyclist. The accumulated lifetime risk of death would be less than 0.5%. This does not appear to be much of a risk amongst all the other hazards of life. It is a good deal lower than the lifetime risk of driving in most industrialized countries—and driving does not benefit health as cycling does. Risk comparisons should be based on hourly risk and annual risk. This will account for the great disparity in mobility between humanpowered and mechanised travel

Most child cyclists are boys, while child pedestrians are split evenly between girls and boys.2 Almost 90% of child cyclist deaths are boys.3 The higher fatality rate for cyclists vis-a-vis pedestrians is due to the preponderance of boy cyclists. It does not mean that cycling is much more dangerous than walking for children.
PTU-202 A case-controlled study demonstrating that changes associated with rectal anastomotic leakage are detectable within 48 hours of surgery
Authors: O Aziz, A Albeyatti, M Derias, N Varsani, H Ashrafian, T Athanasiou, SK Clark, JT Jenkins, RH Kennedy
Journal: Gut (2015)

<h3>Introduction</h3> Anastomotic leakage is generally assumed to occur from approximately 5 days after surgery unless there has been a technical error in anastomotic construction. In order to investigate whether this assumption is correct, clinical changes associated with anastomotic leakage were studied in a homogeneous group of patients. <h3>Method</h3> Individuals were included from a prospectively collected database of patients undergoing laparoscopic total colectomy and ileorectal anastomosis (LTC and IRA) for familial adenomatous polyposis (FAP) between 2006–2013 at a single institution. Patients suffering anastomotic leakage (case group) were compared with controls that did not leak. These controls were selected as the consecutive case before and after each leak case (2 controls for each case). Panel data was collected as repeated measures of continuous post-operative parameters and time-series regression performed using a double subscript structure. A generalised least squares multivariate approach was applied in a random effects setting to calculate correlations for observations with the dependent outcome of anastomotic leak. Regression calculations were performed according to individual observations at each time point to identify outcome correlations. <h3>Results</h3> Data from 95 patients who underwent LTC and IRA for FAP between 2006 and 2013 was available for analysis. All operations were performed laparoscopically within an enhanced recovery programme. 10 patients (10.5%) developed International Classification Grade C leakage (requiring laparotomy), with a mean time to diagnosis of 7.5 +/- 2.6 days. The mean age of the 10 leak patients and 20 controls was 31.9 (+/-17.0) years. There was no significant difference between groups in age, sex, ASA grade, physiology, and operative score. Multivariate analysis of physiological parameters demonstrated a significant difference between leak patients and controls in respiratory rate, urine output, diastolic blood pressure, and heart rate within 48 h of operation. Biochemical parameters, including white cell count, neutrophil count, albumin, and C-reactive protein, did not differ significantly. <h3>Conclusion</h3> Following anastomotic leakage, significant changes in physiological parameters are identifiable within 48 h of surgery. Leakage may occur earlier than has previously been thought and identification may provide opportunities for earlier intervention in order to improve outcome. <h3>Disclosure of interest</h3> None Declared.
Prevention of Rheumatic Fever by Treatment of Streptococcal Infections
Authors: Francis J. Catanzaro, Charles H. Rammelkamp, Robert Chamovitz
Journal: New England Journal of Medicine (1958)

TREATMENT of streptococcal respiratory disease with antibiotics reduces the subsequent attack rate of acute rheumatic fever. In the reported studies1 2 3 4 5 6 a few patients who apparently received adequate therapy for the acute streptococcal infection subsequently had signs of acute rheumatic fever. The fact that in some patients signs of rheumatic activity continued to develop in spite of therapy of the respiratory illness has stimulated the search for better methods of treatment. In addition, if the causes of such therapeutic failures were known, some clues concerning the pathogenesis of rheumatic fever might become evident.Since the number of reported cases of rheumatic . . .
A comparison of treated and untreated simple phobia
Authors: T F Chapman, A J Fyer, S Mannuzza, D F Klein
Journal: American Journal of Psychiatry (1993)

The authors compared 25 treated and 58 untreated subjects with simple phobia uncomplicated by other lifetime anxiety disorders. The treated individuals reported more phobias involving dogs and cats, elevators, and transportation; most had multiple phobias; and many experienced panic attacks in the context of their phobias. The untreated individuals typically reported only one phobia, which was often related to blood-injury and was seldom complicated by panic symptoms.
Case 5-1990
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Charles Trey, Carolyn C. Compton
Journal: New England Journal of Medicine (1990)

Presentation of CaseA 61-year-old woman was admitted to the hospital because of fever, chilliness, and nausea three weeks after an operation for carcinoma of the pancreas.The patient was well until three months earlier, when she began to have persistent low-back pain that was unrelated to position or activity. X-ray study of the spine, a radionuclide bone scan, and an ultrasonographic examination of the pelvis were negative. A barium-enema examination revealed no abnormality except sigmoid diverticula. Anorexia, nausea, and vomiting developed, and one month before admission she first entered this hospital. Physical examination on entry was negative except for . . .
Abstract P2-04-03: SUMO wrestles breast cancer: SUMO posttranslational modification directs breast cancer cell epigenome
Authors: T Bawa-Khalfe, S Kumar, F-M Lin
Journal: Cancer Research (2016)

Abstract Epigenetic reprogramming allows breast cancer (BCa) cells to bypass normal growth checkpoints and acquire an aggressive morphology. Function of critical epigenetic proteins is directed by small ubiquitin-like modifiers (SUMO) posttranslational modification (PTM). Components of the SUMO system are dysregulated in BCa. Our objective is to delineate how changes to SUMO-PTM affect epigenetic programs that coordinate BCa pathology. We report that chromatin-bound SUMO protease SENP7L is upregulated in metastatic tamoxifen-resistant (TamR) and triple-negative BCa. SENP7L facilitates chromatin remodeling that potentiates the growth and invasiveness of these BCa subtypes. SENP7L interacts with and deSUMOylates heterochromatin protein 1 alpha (HP1-alpha/CBX5) to mediates these responses. Canonical models suggest that HP1-alpha reads the histone mark to localize predominantly at constitutive heterochromatin. Our studies challenge the old paradigm as we show that SUMOylated HP1-alpha is enriched outside heterochromatin at euchromatin, including E2F-responsive and mesenchymal gene loci. Recruitment of SUMOylated HP1-alpha supports de novo heterochromatin formation at these loci. However, SUMOylated HP1-alpha is lost in aggressive BCa due to SENP7L induction. Consistently, SENP7L upregulation prompts chromatin de-condensation and gene transcription. Nuclei acid and chemical targeting of SENP7L reduces self-renewal/differentiation properties of TamR mammospheres as well as tumor volume and secondary tumor formation of TamR cells. Hence, SENP7L inhibitors can serve as promising tools to modulate epigenetic abnormalities in TamR BCa. Citation Format: Bawa-Khalfe T, Kumar S, Lin F-M. SUMO wrestles breast cancer: SUMO posttranslational modification directs breast cancer cell epigenome. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-04-03.
Parathyroid Autotransplantation in Primary Parathyroid Hyperplasia
Authors: Samuel A. Wells, George J. Ellis, J. Caulie Gunnells, Arthur B. Schneider, Louis M. Sherwood
Journal: New England Journal of Medicine (1976)

Four patients with primary parathyroid hyperplasia were treated by total parathyroidectomy and autotransplantation of parathyroid tissue into the forearm muscle. All patients remained normocalcemic after vitamin D and oral calcium replacement therapy were stopped at 1 1/2, four, nine and 13 months, respectively. Graft function was documented further by detection of a higher concentration of parathyroid hormone in plasma from the basilic vein draining the graft bed than from the basilic vein in the contralateral arm. Intravenous calcium infusion suppressed parathyroid hormone secretion from the graft whereas hypocalcemia induced by ethylenediaminetetra-acetic acid markedly stimulated hormone release. In two patients histologic examination of a grafted fragment revealed hyperplastic parathyroid tissue. This method of treatment offers a suitable alternative to radical subtotal parathyroidectomy in selected patients with hyperparathyroidism.
A Critical Evaluation of Nalidixic Acid in Urinary-Tract Infections
Authors: Allan R. Ronald, Marvin Turck, Robert G. Petersdorf
Journal: New England Journal of Medicine (1966)

NALIDIXIC acid, one of a series of 1, 8-naphthyridine derivatives, was first synthesized by Lesher et al.1 and introduced into general clinical use in 1964. It is absorbed after oral administration and is excreted by the kidney, resulting in antibacterial levels in the urine well in excess of the minimal inhibitory concentration of most urinary-tract pathogens.2 , 3 The results of preliminary observations demonstrated that the antimicrobial was well tolerated and was effective in eradicating susceptible micro-organisms in the urine.4 5 6 7 8 Although serum levels were variable and occasionally immeasurable3 , 8 one study, at least, indicated that nalidixic acid was highly concentrated in renal tissue. . . .
Reduction of Plasma Homocyst(e)ine Levels by Breakfast Cereal Fortified with Folic Acid in Patients with Coronary Heart Disease
Authors: Manuel R. Malinow, Paul B. Duell, David L. Hess, Peter H. Anderson, Warren D. Kruger, Beverley E. Phillipson, Robert A. Gluckman, Peter C. Block, Barbara M. Upson
Journal: New England Journal of Medicine (1998)

The Food and Drug Administration (FDA) has recommended that cereal-grain products be fortified with folic acid to prevent congenital neural-tube defects. Since folic acid supplementation reduces levels of plasma homocyst(e)ine, or plasma total homocysteine, which are frequently elevated in arterial occlusive disease, we hypothesized that folic acid fortification might reduce plasma homocyst(e)ine levels.
Abstract 5196: Histologic and whole slide quantitative image analysis of lung metastases in a mouse breast cancer model using carboplatin and Nutlin 3A alone and in combination
Authors: Margaret Strack, Eva Tonsing-Carter, Tony Sinn, Tiaishia Spragin, Kacie Peterson, Barbara Bailey, Karen Pollok, George Sandusky
Journal: Cancer Research (2015)

Abstract Breast cancer will affect 1 in 8 women in their lifetime. Approximately 20-30% of all breast cancer cases become metastatic. This study was designed to evaluate the effect of tumor met knockdown with individual and combination drug therapy. In this mouse model, with 3 per group, we used the following chemotherapeutic agents: a vehicle control, carboplatin (20mg/kg i.p.), Nutlin-3a (200mg/kg p.o.) and a combination group with the same doses. Nutlin-3 is a small-molecule inhibitor that binds to the p53-binding pocket of MDM2, and activates the p53 pathway. This has been shown to be effective in mouse models of cancer that have a wild-type p53, including prostate, leukemia and multiple myeloma. The lungs were removed and examined for metastatic lung lesions, fixed in 10% neutral buffered formalin (NBF), processed into a paraffin block, microtomed, and slides were stained with H&amp;E. Ki67 immunostain was performed to clearly define the met lesions and the whole slide was imaged with an Aperio Digital Imaging System. The Image Scope positive pixel algorithm was used to quantitate the met lesions in the lungs. The data revealed upon drug treatment the number of mets in the lungs were unchanged in the carboplatin and nutlin-3a individual treatment groups compared to the vehicle group. The lungs in the combination group had the lowest number of tumors with both visual and quantitative image analysis compared to the vehicle control group. The Aperio automated positive pixel count for Ki67 immunostain was consistent with the H&amp;E pathology read. The values decreased with combination treatment (control vs. combination 20mg/kg carboplatin, 200mg/kg nutlin 3a) and were 6% and 1.7% respectively. It was concluded that mice treated with carboplatin and Nutlin-3a combination therapy had fewer metastatic breast cancer mets in the lungs. The individual drug doses were low compared to previous studies and did not have an effect as was expected. This finding suggests that the combination of a traditional chemotherapy with a small protein inhibitor could inhibit the spread of metastatic breast cancer. Citation Format: Margaret Strack, Eva Tonsing-Carter, Tony Sinn, Tiaishia Spragin, Kacie Peterson, Barbara Bailey, Karen Pollok, George Sandusky. Histologic and whole slide quantitative image analysis of lung metastases in a mouse breast cancer model using carboplatin and Nutlin 3A alone and in combination. [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 5196. doi:10.1158/1538-7445.AM2015-5196