tbuckley/cabot-search huggingface dataset:
Treating before Knowing
Authors: Stephen G. Pauker, Richard I. Kopelman
Journal: New England Journal of Medicine (1992)

A 52-year-old man with a history of mild hypertension and nephrolithiasis presented with progressive dyspnea, productive cough, and fever for three days.The first thing that comes to mind is pneumonia. An upper respiratory tract infection does not usually cause dyspnea unless there is underlying cardiac or pulmonary disease. Hypertensive cardiomyopathy can produce congestive heart failure, but this man has only mild hypertension. Nephrolithiasis can cause advanced renal disease and hypertension but may also be an incidental finding.Two weeks before admission the patient had fatigue, myalgias, and nasal congestion. Four days before admission he noticed shortness of breath and . . .
Terminal Deoxynucleotidyl Transferase Activity in Human Leukemic Cells and in Normal Human Thymocytes
Authors: Ronald McCaffrey, Thomas A. Harrison, Robertson Parkman, David Baltimore
Journal: New England Journal of Medicine (1975)

Peripheral leukocytes from patients with and without leukemia were assayed for presence of terminal deoxynucleotidyl transferase. Activity of this enzyme was detected in circulating leukemic cells from 11 to 13 patients with acute lymphoblastic leukemia, and in one of four with chronic myelogenous leukemia in blast crisis, but not in leukocytes from patients with other kinds of leukemia or in normal leukocytes. Its presence in a patient with chronic myelogenous leukemia in blast crisis lends biochemical support to the suggestion that some patients with chronic myelogenous leukemia undergo a lymphoblastic rather than a myeloblastic crisis. The thymocyte and leukemic-cell enzyme have the same substrate and primer preference. Normal thymocytes and leukemic cells contain two forms of terminal deoxynucleotidyl transferase that can be separated by phosphocellulose chromatography. The enzyme may provide a means for classifying leukemic cells on a biochemical basis independently of classic morphologic and clinical criteria.
Drug Fever Due to Quinidine
Authors: O. Alan Rose, Alfred Vogl, Arnold I. Turtz
Journal: New England Journal of Medicine (1953)

HYPERSENSITIVITY to quinidine is not rare, the symptoms usually taking the form of gastrointestinal disturbances or other reactions similar to those produced by its levo-isomer, quinine. Rarer manifestations include thrombocytopenia, skin rashes and fever.Although all drugs probably can act as allergens, some appear to induce hypersensitivity more readily than others, and only a few oral medications are known to produce drug fever. These include the antipyretics, sulfonamides, the thiouracil derivatives and quinine. Fever as a reaction to quinidine is rare. Since Frey1 introduced quinidine for the treatment of auricular fibrillation more than thirty years ago few cases have been . . .
Thrombolysis in Acute Myocardial Infarction
Authors: H V Anderson, J T Willerson
Journal: New England Journal of Medicine (1993)

Acute myocardial infarction is the most common cause of death in the United States and in almost all Western industrialized countries. Although unadjusted rates of mortality due to myocardial infarction in the United States have been falling in recent years, rates of mortality from all other causes have also been falling, so that the proportion of mortality caused by acute myocardial infarction has not changed. Mortality due to heart disease (mostly infarctions) accounted for 37 percent of all deaths for which a cause could be identified in 1950, for 39 percent in 1960, 1970, and 1980, and for 36 percent . . .
Analysis of dosimetric and radiation safety results of seventeen patients treated with radioimmuno therapy using Iodine 131—Tositumomab for non-Hodgkin’s lymphoma
Authors: M. Nair, R. Mark, P. J. Anderson, T. Neumann
Journal: Journal of Clinical Oncology (2006)

12513 Background: Radioimmunotherapy using radioactive Iodine -131 labeled radioimmuno conjugate called Tositumomab has been used in the treatment of non-Hodgkin’s lymphoma. Radiation dosimetry and safety aspects of this treatment modality are very critical for successful implementation of this treatment. Methods: Since year 2001, we have treated 17 patients using I-131-tositumomab. There were 11 female and 6 male patients at age range of 40 to 82 years. Patient specific dosimetry was performed on all the patents using a tracer dose of I-131. The whole body counts were performed after infusion of 5.0 mCi of I-131-tositumomab and whole body counts were taken at 0, 48 and 178 hours. The total body residence time (TBRT) for 37% of the activity to stay in the body was determined by graphical method. The activity in mCi, for delivering 65 cGy or 75 cGy whole body dose, was calculated based on the TBRT and patient’s weight. Based on the measured exposure rate, we have calculated the total effective dose equivalent (TEDE) to the public. The patients were released to home with radiation safety instructions if TEDE delivered to the public was less than 5.0 mGy. We have studied the platelet count recovery time for all the patients, following treatment. Results: The calculated TBRT ranged from 85 to 175 hours and the the mCi/Kgm varied from 1.4 to 0.6, related inverse proportion with TBRT. For both group of patients, treated with total body dose of 65 cGy and 75 cGy, the mCi/Kgm was the same, for TBRT values exceeding 100 hours. The TEDE to public varied from 1.02 to 3.22 mGy, while the exposure rate measured on the patient at 1 meter was less than the permissible value reported in the literature for safe release. Conclusion: The above results show that the patients can be treated as outpatient using I-131 -tositumomab with radiation safety restrictions lasted for one week. The radiation exposure to the public was less than the maximum permissible dose equivalent. No significant financial relationships to disclose.
Systemic Lupus Erythematosus, Cirrhosis and Ulcerative Colitis after Thymectomy for Myasthenia Gravis
Authors: Richard F. Galbraith, William H. J. Summerskill, John Murray
Journal: New England Journal of Medicine (1964)

THE thymus is accorded important functions in the development of normal and disordered immunologic systems of the body. Not only may immunologically competent lymphocytes with a wide range of specific antigenic activity be derived from the thymus, but the healthy organ may have an inhibitory influence that discriminates effectively against such mutating stem cells and their descendant clones.1 , 2 Although proposing the latter hypothesis, Burnet1 has been unable to find any immunologic disability after thymectomy in the human being. Because of the fundamental significance of such an association a case of systemic lupus erythematosus occurring after thymectomy for myasthenia gravis is . . .
Case 24-2013
Authors: Joi B. Carter, Jeffrey A. Barnes, Bethany L. Niell, Valentina Nardi
Journal: New England Journal of Medicine (2013)

A 53-year-old woman was admitted to the hospital because of erythroderma and lymphadenopathy for 18 months, associated with alopecia, recurrent skin infections, peripheral-blood eosinophilia, and elevated IgE levels. Diagnostic procedures were performed.
Triage, Copayments, and Emergency Department Visits
Authors: Joseph S. Ross
Journal: JAMA Internal Medicine (2016)

imputes missing values.When we repeated our analysis without imputed values, we found similar results.The original intention of triage-to predict the amount of time a patient could safely wait to be seen in the ED-was never intended to completely rule out the possibility of severe illness in a patient considered nonurgent.However, the rhetoric behind the term nonurgent has been often politicized to mean inappropriate, which has implications for both the patient and health care system when these 2 terms are conflated.Our findings highlight the lack of certainty of nonurgent status even when it is determined prospectively by a provider at triage and suggest that caution must be taken when using triage scores beyond their intended purpose.
In vivo synergy combining oxaliplatin with AVE8062, a vascular-disrupting agent
Authors: B. Demers, P. Vrignaud, M. Bissery
Journal: Journal of Clinical Oncology (2006)

13074 Background: AVE8062 is a synthetic, water-soluble compound, analog of Combretastatin A4, currently in Phase I clinical trials. It inhibits tubulin polymerization through binding to the colchicine site of tubulin. In vivo, it induces rapid tumor blood flow shutdown and necrosis, leading to tumor regressions (Proc AACR, 2002). Previously (Proc AACR, 2003), we reported a high synergy resulting from the combination of AVE8062 with either cisplatin or carboplatin in a preclinical in vivo model. We report here the combination data of AVE8062 with oxaliplatin. Methods: A 3-arm dose-response study was performed comparing the single agents and their combination. Synergy was defined as a log cell kill (lck) of at least 1 log superior to the lck of the best single agent. The AVE8062 / oxaliplatin simultaneous combination was evaluated in female BALB/c mice bearing advanced stage (250mg) SC murine colon C51 adenocarcinoma. Drugs were administered IV with 2 intermittent injections, 4 days apart. The combination arm was evaluated over 7 dose levels. Results: At the Highest nontoxic dose (HNTD - 58 mg/kg/inj), AVE8062 was found active: 0.9 lck, 1/5 partial regression (PR) and no complete regression (CR). At the HNTD (7 mg/kg/inj), oxaliplatin was found highly active [5.8 lck, 5/5 CR, no tumor free survivors (TFS)]. The HNTD for the combination (58 mg/kg/inj of AVE8062 with 7 mg/kg/inj of oxaliplatin) was well tolerated with 11.7% body weight loss at nadir. The combination was highly active over the 2 highest dose levels with TFS on day 148 post tumor implantation (4/6 TFS at combination HNTD and 6/6 TFS at 80% HNTD). A high antitumor activity was maintained at 60% HNTD (5.9 lck, 6/6 CR and no TFS). The lowest dose tested, corresponding to 1/10 of the HNTD fractions, was found active with a lck of 1.0 and no regression. Conclusions: The combination of AVE8062 with oxaliplatin was found highly synergistic (superior activity than either of the single agents alone). The combination was well tolerated with a combination toxicity index of 2, indicating that there was no overlap in host toxicity. These data provide a good rationale to perform Phase I combination trials combining AVE8062 with oxaliplatin. [Table: see text]
Abstract 15557: Comparison of 30-day Mortality by Ischemic Times in ST-Elevation Myocardial Infarction Treated With Pre-Hospital Reduced Dose Fibrinolytic Followed by Percutaneous Coronary Intervention versus Percutaneous Coronary Intervention Alone
Authors: Amirreza Solhpour, Kay-Won Chang, Prakash Balan, Stefano M Sdringola, Ali E Denktas, H. Vernon Anderson, Richard W Smalling
Journal: Circulation (2014)

Introduction: The current standard treatment for ST-elevation myocardial infarction (STEMI) is primary percutaneous coronary intervention (PPCI). Early reperfusion results in shorter ischemic time (IT) which reduces mortality. In general, fibrinolysis can be initiated earlier than PPCI. For over 7 years we have used a strategy of field evaluation for STEMI using 12 lead ECGs obtained and transmitted by emergency services personnel with over-read by emergency center physicians. Appropriate STEMI patients receive pre-hospital reduced dose fibrinolytic (10 units reteplase) along with aspirin, clopidogrel, and heparin, and are transported to our center for urgent PCI (termed FAST-PCI strategy). Hypothesis: Patients with STEMI in FAST-PCI group have lower 30-day mortality rate compared with those in PPCI group. Methods: Patients with STEMI at our tertiary center were prospectively included for retrospective analysis. Demographic, clinical, angiographic data and outcomes were investigated. Ischemic time was defined as time from onset of pain to device activation. Patients were divided into groups based on IT (&lt;120, 120-179, 180-239, ≥ 240 minutes). Within each IT group, patients were compared by PPCI and FAST-PCI groups. The primary endpoint was 30-day mortality. Results: Between 02/2007 and 12/2013, we treated 1112 STEMI patients of which 551 (49.5%) underwent FAST-PCI and 561 (50.4%) had PPCI. The two treatment groups in each IT interval were well matched for age, cardiac risk factors, left main and left anterior descending artery infarct. Data are shown in the table. Conclusions: For STEMI patients who presented with IT &lt; 180 minutes, FAST-PCI had reduced 30-day mortality rate compared to PPCI. However, a mortality difference was not seen in patients with IT ≥ 180 minutes between the two treatment groups. This suggests that in patients presenting within 3 hours of onset of symptoms FAST-PCI may confer an advantage over PPCI.
ATCT-16CODEL (ALLIANCE-N0577; EORTC-26081/2208; NRG-1071; NCIC-CEC-2): PHASE III RANDOMIZED STUDY OF RT VS. RT + TMZ VS. TMZ FOR NEWLY DIAGNOSED 1p/19q-CODELETED ANAPLASTIC GLIOMA. ANALYSIS OF PATIENTS TREATED ON THE ORIGINAL PROTOCOL DESIGN
Authors: Kurt Jaeckle, Michael Vogelbaum, Karla Ballman, Caterina Giannini, Kenneth Aldape, Jane Cerhan, Jeffrey Wefel, Donald Nordstrom, Robert Jenkins, Martin Klein, Jeffrey Raizer, Martin van den Bent, Wolfgang Wick, Patrick Flynn, Frederick Dhermain, Gregory Cairncross, Paul Brown
Journal: Neuro-Oncology (2015)

BACKGROUND: CODEL originally included an RT-alone control arm. Following EORTC 26951/RTOG 9402 reports, the original study closed for revision of the control arm to RT + adjuvant PCV. We performed an analysis of pts randomized per the original CODEL design. METHODS: Adults (>18 yr) with newly diagnosed, 1p/19q codeleted WHO grade III anaplastic glioma were randomized to RT (5940 cGy) (Arm A); vs. RT + TMZ (75mg/M2/D +RT; 150-200mg/M2, D1-5 q28D X 6-12 (Arm B); vs. TMZ (150-200 mg/M2, D1-5q28D X 12 (Arm C). Stratification included Age ( 50); Group [North America vs EORTC]; and ECOG status (0-1 vs. 2). Primary endpoint was overall survival. PFS was compared by logrank test (Arm C vs. Arms A + B (pooled). RESULTS: 36 pts (N.A.-53%, EORTC-47%) were randomized (Arm A-12; Arm B-12; Arm C-12), with balance for age, ECOG status, and extent of resection. Grade 3+ toxicity occurred in 25%, 41% and 31% (Arms A, B and C, respectively). No pts withdrew or died from toxicity. All treatment cycles were completed in 92%, 83% and 58% (Arms A, B and C, respectively). Progression during treatment occurred in 5/12 (42%) TMZ alone pts, vs. 0/24 (0%) on RT arms. With median follow-up of 3.4 yrs, 6/12(50%) of the TMZ alone pts have progressed, vs. 2/24(8%) on RT Arms (p = 0.002); death from disease progression occurred in 5%(3/12) TMZ alone pts vs. 4% (1/24) on RT Arms (A-0; B-1). Median PFS was 2.5 yr for TMZ alone vs. not reached for pts on RT Arms. CONCLUSIONS: In this preliminary analysis, patients receiving TMZ alone experienced shorter PFS and time to death from tumor progression, compared to those receiving RT alone or RT + TMZ. Accordingly, the Alliance DSMC recommended closure of Arm C. CODEL has been revised to a two-arm comparison of RT + adjuvant PCV vs. RT + concomitant/adjuvant TMZ. (Support: U10CA180821)
High-Density Lipoprotein Proteomic Composition, and not Efflux Capacity, Reflects Differential Modulation of Reverse Cholesterol Transport by Saturated and Monounsaturated Fat Diets
Authors: Marcella O’Reilly, Eugene Dillon, Weili Guo, Orla Finucane, Aoibheann McMorrow, Aoife Murphy, Claire Lyons, Daniel Jones, Miriam Ryan, Michael Gibney, Eileen Gibney, Lorraine Brennan, Margarita de la Llera Moya, Muredach P. Reilly, Helen M. Roche, Fiona C. McGillicuddy
Journal: Circulation (2016)

Acute inflammation impairs reverse cholesterol transport (RCT) and reduces high-density lipoprotein (HDL) function in vivo. This study hypothesized that obesity-induced inflammation impedes RCT and alters HDL composition, and investigated if dietary replacement of saturated (SFA) for monounsaturated (MUFA) fatty acids modulates RCT.Macrophage-to-feces RCT, HDL efflux capacity, and HDL proteomic profiling was determined in C57BL/6j mice following 24 weeks on SFA- or MUFA-enriched high-fat diets (HFDs) or low-fat diet. The impact of dietary SFA consumption and insulin resistance on HDL efflux function was also assessed in humans. Both HFDs increased plasma (3)H-cholesterol counts during RCT in vivo and ATP-binding cassette, subfamily A, member 1-independent efflux to plasma ex vivo, effects that were attributable to elevated HDL cholesterol. By contrast, ATP-binding cassette, subfamily A, member 1-dependent efflux was reduced after both HFDs, an effect that was also observed with insulin resistance and high SFA consumption in humans. SFA-HFD impaired liver-to-feces RCT, increased hepatic inflammation, and reduced ABC subfamily G member 5/8 and ABC subfamily B member 11 transporter expression in comparison with low-fat diet, whereas liver-to-feces RCT was preserved after MUFA-HFD. HDL particles were enriched with acute-phase proteins (serum amyloid A, haptoglobin, and hemopexin) and depleted of paraoxonase-1 after SFA-HFD in comparison with MUFA-HFD.Ex vivo efflux assays validated increased macrophage-to-plasma RCT in vivo after both HFDs but failed to capture differential modulation of hepatic cholesterol trafficking. By contrast, proteomics revealed the association of hepatic-derived inflammatory proteins on HDL after SFA-HFD in comparison with MUFA-HFD, which reflected differential hepatic cholesterol trafficking between groups. Acute-phase protein levels on HDL may serve as novel biomarkers of impaired liver-to-feces RCT in vivo.
Intrathecal drug delivery versus comprehensive medical management as it may impact inpatient length of stay, readmission, and inpatient cost of care
Authors: J. D. Isaacs, L. J. Stearns, W. H. Poling, D. Milton, J. Nasternak, C. Romano
Journal: Journal of Clinical Oncology (2006)

18520 Background: Long lengths of stay (LOS) and high readmission rates partly explain the high medical costs of treating cancer patients. Uncontrolled pain is the number two reason for hospital readmission. Aggressive measures and treatment strategies for relieving intractable cancer pain can require the implantation and management of intrathecal (IT) drug delivery systems. The objective was to examine LOS, episodes of readmission, intensive care (ICU) stays, and discharge status among patients treated with IT versus comprehensive medical management (CMM) for pain. Methods: Retrospective case-control medical record review methods were employed. Sixty-three randomly selected cancer patients who received an IT were matched on gender, age group, and primary diagnosis to 63 who did not. Results: The total LOS for the 63 non-IT patients was 567 days. The total LOS for the 63 IT patients was 301 days. The mean LOS among the non-IT patients was 9 days. The mean LOS among the IT patients was 4.7 days. Total LOS for the non-IT patients was statistically significantly higher. Among the 63 non-IT patients 94 total inpatient episodes were experienced. Among the 63 IT patients 68 total inpatient episodes were experienced. The likelihood of a non-IT patient readmitting was nine-fold higher than the IT patients and statistically significantly different. The total Intensive Care Unit (ICU) days for the 63 non-IT patients were 60 days. The total ICU days for the 63 IT patients were 30 days. The total ICU for the non-IT patients was not statistically significantly higher. The likelihood of a non-IT patient expiring while an inpatient was fourteen-fold higher than the IT patients and was statistically significantly different. The average cost per episode was 22% higher among the IT group versus the non-IT group. Conclusions: The implantable IT system for pain management among cancer patients experiencing intractable pain may be a significant influence on patient LOS, readmission, and ICU episodes even though it represents a 22% increase in average inpatient costs per episode. Controlled studies examining these hospital indicators as primary outcomes for these patients by evaluating the IT drug delivery system as compared to CMM are warranted. No significant financial relationships to disclose.
Severe Pseudohypocalcemia after Gadolinium-Enhanced Magnetic Resonance Angiography
Authors: Cornelius J. Doorenbos, Akin Ozyilmaz, Merel van Wijnen
Journal: New England Journal of Medicine (2003)

To the Editor: Magnetic resonance imaging is increasingly used to avoid the radiation used in computed tomographic scanning. Gadolinium contrast medium allows vascular imaging without the nephrotoxic effects associated with conventional contrast material.1 A 62-year-old man with suspected renal-artery stenosis underwent magnetic resonance angiography (MRA) after receiving 40 ml of gadolinium (Omniscan, Amersham Health). Analysis of a blood sample obtained immediately after the MRA study revealed a plasma calcium level of only 4.4 mg per deciliter (normal range, 8.8 to 10.6). Six hours later, his calcium level was 7.2 mg per deciliter. The patient had no symptoms, and Chvostek's and . . .
A One-Year Trial of Lamivudine for Chronic Hepatitis B
Authors: Ching-Lung Lai, Rong-Nan Chien, Nancy W.Y. Leung, Ting-Tsung Chang, Richard Guan, Dar-In Tai, Keng-Yeen Ng, Pui-Chee Wu, Julie C. Dent, Judy Barber, Sally L. Stephenson, D. Fraser Gray
Journal: New England Journal of Medicine (1998)

In preliminary trials, lamivudine, an oral nucleoside analogue, has shown promise for the treatment of chronic hepatitis B. We conducted a one-year, double-blind trial of lamivudine in 358 Chinese patients with chronic hepatitis B. The patients were randomly assigned to receive 25 mg of lamivudine (142 patients), 100 mg of lamivudine (143), or placebo (73) orally once daily. The patients underwent liver biopsies before entering the study and after completing the assigned treatment regimen. The primary end point was a reduction of at least two points in the Knodell necroinflammatory score.
Acyclovir Halts Progression of Herpes Zoster in Immunocompromised Patients
Authors: Henry H. Balfour, Bonnie Bean, Oscar L. Laskin, Richard F. Ambinder, Joel D. Meyers, James C. Wade, John A. Zaia, Dorothee Aeppli, L. Edward Kirk, Anthony C. Segreti, Ronald E. Keeney
Journal: New England Journal of Medicine (1983)

We conducted a placebo-controlled, double-blind study of acyclovir therapy for acute herpes zoster in immunocompromised patients. Of the 94 patients enrolled in the study, 52 had localized skin lesions at entry, and 42 had disseminated cutaneous zoster. A one-week course of intravenous acyclovir (1500 mg per square meter of body-surface area per day) halted progression of zoster in both groups, as determined by development or progression of cutaneous dissemination, development of visceral zoster, or proportion of cases deemed treatment failures. Significantly fewer patients treated with acyclovir within the first three days after the onset of exanthem had complications of zoster, as compared with patients treated with placebo (P = 0.02 by Fisher's exact test), but acyclovir also stopped progression of zoster in patients treated after three days of rash (P = 0.05 by Fisher's exact test). Acyclovir recipients with disseminated cutaneous zoster had a significantly accelerated rate of clearance of virus from vesicles, as compared with placebo recipients (P = 0.05 by the Breslow test).
Immunochemical Evidence for the Development of an Acquired Hypogammaglobulinemic State
Authors: John B. Robbins, Donald V. Eitzman, Elliot F. Ellis
Journal: New England Journal of Medicine (1966)

TO account for the change in health of previously "normal" persons, characterized by susceptibility to infection and low serum immunoglobulins, the term "acquired" hypogammaglobulinemia has been proposed.1 2 3 The validity of this classification was substantiated by morphologic evidence recently offered by Charache et al.4 These workers documented the change of a normal lymphoid architecture, observed in an appendix removed in surgery, eight years before the appearance of the histologic lesion characteristic of the hypogammaglobulinemic state. To provide further data consistent with this concept of "acquired" hypogammaglobulinemia, we report a case in which, during the past four years, nearly complete loss of . . .