tbuckley/cabot-search huggingface dataset:
Acquired Defect in Interleukin-2 Production in Patients with Type I Diabetes Mellitus
Authors: William A. Kaye, M.N.S. Adri, J. Stuart Soeldner, Steven L. Rabinowe, Antoine Kaldany, C. Ronald Kahn, Bruce Bistrian, S. Srikanta, Om P. Ganda, George S. Eisenbarth
Journal: New England Journal of Medicine (1986)

Deficient production of interleukin-2 has been reported in Type I diabetes, but its cause has not been elucidated. We therefore measured interleukin-2 production in 27 patients with Type I diabetes, 20 patients with Type II diabetes (6 requiring insulin), 5 monozygotic twin pairs discordant for Type I diabetes, and 10 nondiabetic persons with islet-cell antibodies. Interleukin-2 production was decreased in patients with Type I diabetes as compared with controls (35.8±2.5 vs. 61.6±4.6 percent, P<0.001). Interleukin-2 production did not differ between patients with Type II diabetes and controls, regardless of whether the patients used insulin. Twins with Type I diabetes had decreased interleukin-2 production as compared with normal controls (33.2±5.4 vs. 61.6±4.6 percent, P<0.001) and with their nondiabetic twins (33.2±5.4 vs. 54.5±3.4 percent, P<0.005). lnterleukin-2 production in nondiabetic twins and in nondiabetic persons with islet-cell antibodies was normal. There was no correlation between glycosylated hemoglobin levels and interleukin-2 production in any diabetic group. We conclude that patients with Type I diabetes have an acquired defect in interleukin-2 production, whereas patients with Type II diabetes do not, and that this defect is not correlated with an ongoing autoimmune process, with hyperglycemia, or with insulin administration or oral hypoglycemic therapy. Thus, the defect appears to be related to marked beta-cell destruction, although not to the metabolic consequences thereof or the responsible autoimmune process. (N Engl J Med 1986; 315: 920–4.)
Case 7-1997
Authors: Richard B. Colletti, Carolyn C. Compton
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 14-year-old girl was admitted to the hospital because of recurrent rectal bleeding.She had been in excellent health until three years earlier, when she began to pass blood-tinged stools. The bleeding increased during the course of several days. A proctosigmoidoscopic examination showed no abnormality. Hydrocortisone enemas were followed by the cessation of bleeding. She was then well until 45 days before admission, when her stools again became blood-tinged, and she later passed frank blood rectally. A colonoscopic examination did not reveal the source of the bleeding. Hematochezia continued. Twenty-seven days before admission, the results of an . . .
Treatment of Sickle Cell Anemia with Hydroxyurea and Erythropoietin
Authors: Mark A. Goldberg, Carlo Brugnara, George J. Dover, Lidia Schapira, Samuel Charache, H. Franklin Bunn
Journal: New England Journal of Medicine (1990)

Hydroxyurea increases the production of fetal hemoglobin (hemoglobin F) in patients with sickle cell anemia and therefore has the potential for alleviating both the hemolytic and vaso-occlusive manifestations of the disease. There is preliminary evidence that recombinant human erythropoietin may also increase hemoglobin F production.
Analysis of early hypertension (HTN) and clinical outcome with bevacizumab (BV).
Authors: H. Hurwitz, P. S. Douglas, J. P. Middleton, G. W. Sledge, D. H. Johnson, D. A. Reardon, D. Chen, O. Rosen
Journal: Journal of Clinical Oncology (2010)

3039 Background: HTN is associated with anti-VEGF treatment (Tx), but this association has not been well studied. To assess the prognostic and predictive importance of BV-related HTN, a systematic, comprehensive analysis of HTN and clinical outcome was conducted on all placebo- controlled phase III, company-sponsored BV studies. Methods: Patient (pt)-specific data, including blood pressure (BP), concomitant medications, pt characteristics, and clinical outcomes, were available from approximately 5,900 patients across 6 studies of metastatic cancer (CA): AVF2107g, NO16966 (colorectal CA); AVADO, RIBBON-1 (breast CA); AVAiL (non-small cell lung CA); AVOREN (renal cell CA). The primary HTN endpoint was an SBP increase >20 mmHg or DBP increase >10 mmHg within the first 60 days of Tx. Secondary endpoints included other predefined cut-points, HTN as a continuous variable, and NCI CTC grade of HTN. Multivariate Cox regression models were used to assess the correlation between BP changes and progression-free and overall survival (PFS, OS) in the control groups (prognostic), and the difference of such correlations between the BV-treated groups and control groups (predictive). Hazard ratios (HR) and p values were calculated. Results: In 5 of 6 studies, HTN during Tx was not predictive of clinical benefit or prognostic for the course of disease, either in BV-treated groups or the control groups. For AVF2107g, HTN predicted superior PFS and OS in the BV group and worse OS in the control group. Across all studies, results were similar for all secondary HTN endpoints. HR and p values for the predictive and prognostic importance of HTN are shown in the Table. Conclusions: HTN during Tx does not predict clinical benefit from BV based on PFS or OS. Also, baseline HTN and HTN during Tx do not appear to have general prognostic importance in pts with advanced CA. AVF2107g NO16966 AVADO* RIBBON-1 AVAiL* AVOREN Prognostic HR (p value) for PFS 1.20 (0.14) 1.00 (>0.99) 1.09 (0.66) 1.16 (0.34) 0.95 (0.69) 1.11 (0.45) OS 1.36 (0.02) 0.89 (0.49) 1.02 (0.95) 1.40 (0.11) 0.85 (0.33) 0.87 (0.45) Predictive HR (p value) for PFS 0.55 (0.0008) 0.81 (0.18) 0.91 (0.72) 0.82 (0.26) 1.04 (0.83) 0.81 (0.29) OS 0.43 (<0.0001) 0.80 (0.36) 0.91 (0.85) 0.62 (0.05) 1.32 (0.21) 0.98 (0.95) * 5 mg/kg/week Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Roche Roche Genentech
EPC2407, a new beta-tubulin vascular disrupting agent with potent apoptosis and cell growth inhibition
Authors: S. P. Anthony, D. Von Hoff, J. K. Whisnant, B. Y. Tseng
Journal: Journal of Clinical Oncology (2007)

14043 Background: Compounds which bind to colchicine-like sites of microtubules have contributed greatly to the armamentarium of cancer therapies. But new modes of administration of taxanes and potent new vascular disruption agent molecules such as combretastatin continue to challenge drug development for ways to improve the therapeutic index in this important class. EPC2407 is a novel 4-aryl chromene of nM anti-tumor potency; it is crossing the translational bridge based on an array of preclinical anti-tumor pharmacology and supported by multiple toxicology trials which included drug exposure data. Methods: Vascular disrupting agents demand careful preclinical workup. What we have done is summarized in the table below. This data is from cellular metabolic, cell proliferation, vascular endothelial, in vivo tumor, and animal toxicokinetic and safety studies. Results: Please see table below of the preclinical experiments. Conclusions: A Phase I clinical trial has been designed and initiated to replicate the safety margin shown by the analysis of preclinical drug exposure data. The critical safety issue for human dosing was the dose exposure which might produce the well known ECG abnormality of delayed repolarization or prolonged QTc. A dose related QTc effect was demonstrated in cynomolgus monkeys after a 2 min infusion which achieved acute plasma exposures higher than 3836 nM. These effects were dose related and persisted only through 4 short half-lives of the parent compound. Initial human analysis fails to show any prolongation of the QTc. [JW1] [JW1]THE END HERE, all else was draft. [Table: see text] No significant financial relationships to disclose.
Case 9-2005
Authors: David M. Systrom, Conrad Wittram
Journal: New England Journal of Medicine (2005)

A 67-year-old man was admitted to the hospital with acute respiratory failure. He had never smoked, had not traveled, but had recently been exposed to bird droppings. Cultures and serologic test results were negative. With antibiotic therapy and respiratory support, his symptoms rapidly improved over 48 hours. Three days after discharge, his symptoms returned shortly after using his hot tub, and again abated rapidly after admission to his local hospital.
Aerosol Therapy of Respiratory Disease
Authors: Vernon Bryson, Edwin J. Grace
Journal: New England Journal of Medicine (1947)

AEROSOL therapy may be defined as the medicinal administration of fine solid particles or liquid mists as inhalants. The method has never been widely used in the treatment of disease, although asthmatic patients have been given symptomatic relief with epinephrine aerosols for many years. To anyone familiar with the basic studies on the subject,1 2 3 4 5 6 7 the administration of antibiotics as aerosols appears to be a logical and necessary development. It may be anticipated that the advantages of simple administration and a relatively constant rate of absorption will eventually induce medical investigators to explore more fully the process of aerosolization as a . . .
Case 49-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, J.Y. Wei, E.J. Mark
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 70-year-old man was admitted to the hospital because of coronary artery disease and congestive heart failure.There was a long history of hypertension with exertional dyspnea of 10 years' duration and angina pectoris with increasing dyspnea of 4 months' duration. Seven weeks before entry, examination revealed weight loss and anemia, with a hematocrit of 33 percent. The cardiac findings and results of pulmonary-function tests are presented in Tables 1 and 2. A cough productive of rusty sputum was treated as pneumonia with penicillin, but a chronic productive cough persisted. Furosemide, verapamil, isosorbide dinitrate, and nitroglycerin were administered. The . . .
Impact of IL-8 and Heat Shock Protein 60 Kda on Fertility of Chronic Prostatitis Patients in Kiev, Ukraine
Authors: George N. Drannik, I.I. Gorpinchenko, T.V. Poroshina, K.R. Nurimanov, Vladimir S. Savchenko, Lawrence M. DuBuske
Journal: Journal of Allergy and Clinical Immunology (2016)
A Comparative Study of Pregnenolone, 21-Acetoxypregnenolone and ACTH
Authors: Heinrich G. Brugsch, Ralph A. Manning
Journal: New England Journal of Medicine (1951)

THE evaluation of new drugs in the treatment of rheumatoid arthritis and spondylitis has become a grave responsibility of the medical profession. Since the scarcity of ACTH and cortisone, as well as their limitations and side-effects, is now generally known, favorable recommendations of new drugs based on clinical experience are likely to cause unrest and new hopes among those suffering from disabling rheumatic disease.Certain drugs that have been the object of recent clinical studies and subsequent publicity are steroids of the pregnenolone, pregnenolone acetate, 21-acetoxypregnenolone and pregnenolone diacetate group (also known by various brand names such as prenone, artisone . . .
Alpha frequency in schizophrenia: an association with enlarged cerebral ventricles
Authors: C N Karson, R Coppola, D G Daniel
Journal: American Journal of Psychiatry (1988)

Low alpha frequency (less than 10.2 Hz) occurred more frequently in medication-free schizophrenic patients than in normal control subjects, as determined by quantitative EEG analysis. Furthermore, those patients with low alpha frequency had significantly larger lateral ventricles, as measured by CT scan, than did other schizophrenic patients (mean +/- SD ventricle-brain ratios = 9.8 +/- 1.9 versus 5.0 +/- 2.4; p less than 0.01). This finding suggests the existence of a relationship between cerebral structural pathology and the alpha rhythm that may be based on involvement of alpha-generating structures which border the cerebral ventricles. Future EEG studies of schizophrenia may resolve these questions in the context of other brain findings.
Enhancement by Phenobarbital and Diphenylhydantoin of Carbon Monoxide Production in Normal Man
Authors: Ronald F. Coburn
Journal: New England Journal of Medicine (1970)

Nine normal human subjects were given a seven-day course of phenobarbital or diphenylhydantoin. With phenobarbital and diphenylhydantoin respectively, total body heme, as estimated by carbon monoxide dilution, rose to an average of 114.8 (p less than 0.05) and 109 (p less than 0.05) per cent of control levels. Rates of heme catabolism, determined by measurement of rates of carbon monoxide production, increased an average of 174 and 214 per cent of normal (p less than 0.01) with these two agents. The agents appear to have induced hepatic heme, and after "induction," catabolism of hepatic heme contributed over 50 per cent of the total carbon monoxide production.
RECIST (Response Evaluation Criteria in Solid Tumors) applied to response in lymphoma
Authors: S. Assouline, E. Eisenhauer
Journal: Journal of Clinical Oncology (2004)

6606 Background: RECIST utilizing unidimensional tumor measures are widely accepted for assessing response in solid tumor clinical trials. We have investigated whether these criteria can be applied to response assessment in lymphoma. However, to do so, complete response (CR) criteria were modified to include the following: a) baseline node(s) >15 mm must regress to ≤15 mm; b) nodes 10–15 mm must regress to normal; and c) enlarged spleen or liver is non-measurable and must return to normal size. Further, CR unconfirmed (CRu) by IWC was considered PR by RECIST. Methods:Using RECIST with these modifications, we determined clinical response in three phase II lymphoma trials of the National Cancer Institute of Canada Clinical Trials Group and compared results with response as determined by the International Working Criteria (IWC) (Cheson B, JCO 1999). Kappa estimated agreement of response (CR+PR+CRu) and non-response (PR+SD) between RECIST and IWC. Pearson's coefficient estimated correlation between changes in uni- and bidimensional measurements for responses based on these measurements alone. Results: 115 pts were evaluable, 92 with non-Hodgkin's and 23 with Hodgkin's lymphoma. By IWC, 14 achieved CR, 2 CRu, 32 PR, 52 SD, 15 PD, for an overall response (OR) of 42%. By RECIST, there were 14 CR, 39 PR, 47 SD, 15 PD, and OR 46%. κ=0.81 (95% CI: 0.70, 0.91), Pearson's r=0.81(95% CI: 0.71, 0.88) for changes in uni- and bidimensional measurements (n=75) for the two instruments. Conclusions: After some adaptations, applying RECIST to lymphoma yields near identical OR as IWC. There is high agreement between responses determined using uni- and bidimensional measurements. The benefits of RECIST over IWC include: familiarity among cancer trialists, simplicity of measuring unidimensional disease and providing follow-up measurements only for nodes >15 mm at baseline, and ability to include patients whose lymphoma is extranodal only. RECIST do not include CRu as a response category but OR is the likely estimate of interest in phase II clinical trials of novel agents. We therefore propose adapted RECIST be further studied for assessment of response in lymphoma. No significant financial relationships to disclose.
Bronchomediastinal Fistula after Endobronchial Ultrasound–guided Transbronchial Needle Aspiration
Authors: Justin Wong, Cristina Gutierrez, Vickie R. Shannon, George A. Eapen, Saadia A. Faiz
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Bronchomediastinal Fistula after Endobronchial Ultrasound–guided Transbronchial Needle Aspiration Justin Wong, Cristina Gutierrez, Vickie R. Shannon, George A. Eapen, and Saadia A. Faiz Division of Pulmonary, Critical Care, and Sleep Medicine, The University of Texas Health Science Center at Houston, Houston, Texas; and Department of Critical Care Medicine and Department of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
Clinical Course of Hyperbilirubinemia in Premature Infants
Authors: Kenneth Hugh-Jones, Joan Slack, Kenneth Simpson, Aaron Grossman, David Yi-Yung Hsia
Journal: New England Journal of Medicine (1960)

THE plasma of the human infant at birth contains a concentration of bilirubin that on the average considerably exceeds the figures for normal adults; the concentration increases rapidly after birth to reach a peak at two to five days and thereafter slowly decreases.1 2 3 4 It is believed that the hyperbilirubinemia occurs because of a relative lack of glucuronyl transferase activity in the liver5 6 7 or inhibition of this enzyme.8 In many premature infants and some full-term infants this hyperbilirubinemia can reach levels comparable to those in cases of blood incompatibility.3 , 4 Exchange transfusion in the treatment of hemolytic disease due to Rh or . . .
166P: Non-small cell lung cancer (NSCLC) patients with rare or complex epidermal growth factor receptor (EGFR) mutations: A single institution series
Authors: G. Pasello, V. Polo, S. Frega, M. Lorenzi, S. Indraccolo, M. Fassan, L. Bonanno, N. Nannini, P.F. Conte, F. Calabrese
Journal: Journal of Thoracic Oncology (2016)
Cigarette Smoking and the Risk of Endometrial Cancer
Authors: Samuel M. Lesko, Lynn Rosenberg, David W. Kaufman, Susan P. Helmrich, Donald R. Miller, Brian Strom, David Schottenfeld, Neil B. Rosenshein, Robert C. Knapp, John Lewis, Samuel Shapiro
Journal: New England Journal of Medicine (1985)

Because of evidence of reduced estrogen excretion in the urine of women who smoke cigarettes and evidence linking estrogen levels to the risk of cancer of the female reproductive system, we evaluated the risk of endometrial cancer in relation to cigarette use in a hospital-based case-control study of 510 women with endometrial cancer (cases) and 727 women with other cancers (controls). The rate-ratio estimate (relative risk) for current smokers as compared with women who had never smoked was 0.7 (95 per cent confidence interval, 0.5 to 1.0), and for former smokers the estimate was 0.9 (0.6 to 1.2). For women currently smoking 25 or more cigarettes per day, the rate-ratio estimate was 0.5 (0.3 to 0.8). The effect of current smoking of at least 25 cigarettes per day appeared to be confined to postmenopausal women, among whom the estimate was 0.5 (0.2 to 0.9). Among premenopausal women the estimate was 0.9 (0.4 to 2.2), but the difference between these two estimates could have been due to chance. The data suggest that women who smoke heavily may have a lower risk of endometrial cancer than nonsmokers. The present findings do not have direct public health importance since cigarettes, overall, have serious deleterious effects. However, if these results are confirmed, elucidation of the underlying mechanisms whereby smoking reduces the risk would be of interest and might be useful in the development of strategies for preventing endometrial cancer.
Role Of Long Pentraxin 3 (PTX3) In Wound Closure Induced By Bone Marrow-Derived Mesenchymal Stromal Cells
Authors: Claudia Cappuzzello, Andrea Doni, Erica Dander, Fabio Pasqualini, Manuela Nebuloni, Barbara Bottazzi, Alberto Mantovani, Andrea Biondi, Cecilia Garlanda, Giovanna D'Amico
Journal: Blood (2013)
P38 Improved mortality and outcomes for patients requiring non-invasive ventilation managed in a dedicated hyper acute medical unit
Authors: T Buttle, H Chreif, H Woods, S Lohani
Journal: Thorax (2015)

<h3>Introduction</h3> Non-invasive ventilation (NIV) improves survival and outcomes in hypercapnic (type 2) respiratory failure. Following below average performance in a district hospital in the BTS national NIV audit, NIV delivery moved from acute medical and respiratory wards to a new hyper-acute medical unit (HAMU) providing level 1 nursing care and NIV. The unit is supervised by Respiratory Physicians and a dedicated NIV-trained nursing team, to improve outcomes for acutely unwell patients. A close working relationship with the Critical care team, and physical proximity to the Intensive care unit ensures rapid joint assessment and transfer of complex patients requiring invasive monitoring or intubation. <h3>Aims and objectives</h3> To compare NIV success and mortality for patients with acute type 2 respiratory failure requiring NIV, before and after introduction of HAMU. <h3>Method</h3> Data was collected for all patients in acute type 2 respiratory failure requiring NIV, for nine months before (2011–2012) and after (2012–2013) the HAMU was opened. Baseline characteristics (age, gender, performance and smoking status) were recorded. NIV success and mortality were compared and analysed. Patients requiring intubation on admission were not included. <h3>Results</h3> Baseline characteristics in both groups were similar, and comparable to national figures. NIV was successful in 56% (28/53) before, improving to 74% (43/58) after (p &lt; 0.05). National success rates from BTS 2013 data were 66.5%. All-cause mortality improved from 42% (22/53), to 24% (14/58) (p &lt; 0.05). National all-cause mortality rate was 34% in 2013. Transfer to Critical care was low in both groups (1/53 pre, and 1/53 post). <h3>Conclusions</h3> NIV success and mortality rates improved significantly following opening of the HAMU. Following establishment of the HAMU, success rates are also clearly better than national comparators for 2013. NIV delivery in a dedicated unit with highly trained nurses and dedicated respiratory medical input improves outcomes in acute Type 2 Respiratory failure.
Primary Care Medicine in Canada
Authors: Michael E. Whitcomb, J.P. Desgroseilliers
Journal: New England Journal of Medicine (1992)

IN recent years, analysts in both the academic and policy-making communities have come to believe that the supply of primary care physicians in the United States is inadequate to meet the needs of the population.1 , 2 In the light of this perception, the declining interest of graduates of U.S. medical schools in careers in primary care medicine is viewed with alarm. Between 1986 and 1991, the number of graduates matched to residencies (internal medicine, pediatrics, and family medicine) that might lead to careers in primary care medicine decreased by 19 percent.3 , 4 If the current trend persists, the percentage of U.S. physicians . . .
Contribution of<i>BRCA1</i>Mutations to Ovarian Cancer
Authors: John F. Stratton, Simon A. Gayther, Paul Russell, Jo Dearden, Martin Gore, Peter Blake, Doug Easton, Bruce A.J. Ponder
Journal: New England Journal of Medicine (1997)

Inherited mutations in the BRCA1 gene confer a high risk of breast and ovarian cancer in some families. To determine the contribution of BRCA1 mutations to ovarian cancer in the general population, we analyzed DNA samples from a consecutive series of women with ovarian cancer seen at one center.
Case 27-1976
Authors: Harvey B. Simon, Karl H. Proppe
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 32-year-old man was admitted to the hospital because of meningitis.He was well until five years previously, when fatigue, weight loss, sweats and fever developed. A lymph-node biopsy disclosed Hodgkin's disease, nodular-sclerosis type. An x-ray film of the chest demonstrated hilar and paratracheal lymphadenopathy; a lymphangiographic examination was negative. A staging laparotomy revealed involved celiac-axis lymph nodes and gross evidence of disease in the spleen, which was removed; a liver biopsy was negative. A diagnosis of Hodgkin's disease, Stage IIIB, was made. A course of MOPP (nitrogen mustard, Oncovin [vinblastine], procarbazine and prednisone) was given, without . . .