tbuckley/cabot-search huggingface dataset:
Theophylline Disposition in Patients with Hepatic Cirrhosis
Authors: Kenneth M. Piafsky, Daniel S. Sitar, Robert E. Rangno, Richard I. Ogilvie
Journal: New England Journal of Medicine (1977)

To determine the role of liver dysfunction in theophylline toxicity, we administered single intravenous doses of the drug to nine patients with cirrhosis and observed its disposition over a period of 24 to 48 hours. As compared to 19 normal subjects, these patients had a prolonged plasma half-life (mean, 25.6 vs. 6.7 hours) and a decreased plasma clearance (mean, 0.042 vs. 0.062 liter[kg-1]hr-1). Volumes of distribution of theophylline in the cirrhotic patients (central-compartment volume of 0.330, and steady-state volume of distribution of 0.785 liter per kilogram) did not substantially differ from normal (0.246 and 0.508 respectively). Plasma theophylline binding in three patients with cirrhosis averaged 36.8 per cent as compared to 52.6 per cent in four normal subjects. There was no correlation between any laboratory test of liver function and the plasma theophylline half-life, except for serum albumin (r = 0.92, P less than 0.001). The variable capacity to eliminate theophylline precludes the use of usual maintenance dose schedules for bronchodilation in cirrhosis.
The Effect of Position on Periodic Breathing in Chronic Cardiac Decompensation
Authors: M. D. Altschule, Arnold Iglauer
Journal: New England Journal of Medicine (1958)

DISSCUSSIONS of the relation between position and respiratory symptoms in congestive heart failure are usually centered about the symptom of orthopnea. The purpose of the present report is to describe the effect of position on another manifestation — that is, periodic breathing.Material and MethodsFifteen experiments were carried out on patients with chronic cardiac decompensation. Their ages ranged from thirty-four to seventy-three years; all but 1 were men. The etiologic diagnosis was rheumatic or arteriosclerotic heart disease.Patients were unselected, except that they were not included if unable to tolerate flat or almost flat positions for at least six . . .
Unusual Manifestations of Carcinoma of the Esophagus
Authors: George T. Wohl, Bernard H. Pastor, Samuel L. Karr
Journal: New England Journal of Medicine (1955)

APPROXIMATELY 20 per cent of esophageal carcinomas are nonobstructing when first seen and many remain so throughout the course of the disease.1 2 3 4 For this reason dysphagia, usually the most prominent symptom, may be a late or terminal manifestation.1 , 5 , 6 In the nonobstructing lesions unusual presenting symptoms often occur as a result of extension to contiguous structures or as a consequence of distant metastasis. In either event the patient's complaints may seem unrelated to the esophagus, and the correct diagnosis may be missed or delayed.Local extension can cause hoarseness, pain or cough from involvement of the recurrent laryngeal nerve or tracheobronchial . . .
Planned Parenthood stops taking reimbursement for fetal tissue donations
Authors: Michael McCarthy
Journal: BMJ (2015)

Planned Parenthood no longer accepts reimbursement for processing fetal tissue donated to medical research after abortions, the organization said on 13 October. Under the new policy Planned Parenthood will continue to supply the tissue to medical researchers but without seeking to recover the costs of collection and processing.

The organization has been under attack from state and federal lawmakers since June when an anti-abortion group released a video in which Planned Parenthood officials were secretly recorded discussing the reimbursements they would seek for processing fetal tissue with actors posing …
P154 Evaluation of Inhaler Technique Mastery for Budesonide Formoterol Spiromax® Compared with Symbicort Turbohaler® in Adult Patients with Asthma: Primary Results From the Easy Low Instruction Over Time [ELIOT] Study: Abstract P154 Table 1
Authors: H Chrystyn, R Dekhuijzen, C Rand, S Bosnic-Anticevich, N Roche, F Lavorini, V Thomas, J Steele, P Raju, D Freeman, I Small, J Canvin, D Price
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Technical errors in the use of inhalers are associated with poor asthma control. This study evaluated achievement of mastery in a training environment using a randomised cross-over design (stage 1), followed by randomization into a prospective 12-week trial to assess maintenance of mastery in patients receiving inhaled corticosteroids (ICS)/long-acting β<sub>2</sub>-agonists (LABA) via SPIROMAX versus ICS/LABA received via TURBOHALER (stage 2). <h3>Methods</h3> Patients with asthma were randomised to a 6-step training protocol using empty Spiromax and empty Turbohaler devices. The proportion of patients achieving and maintaining inhaler mastery, respectively defined as the absence of health care professional (HCP)-observed errors by training step 3 (instructional video) in stage 1, and the absence of HCP-observed errors after 12 weeks of inhaler use in stage 2, were analysed using logistic regression. The maintenance of independent expert video-observed inhaler mastery was analysed using logistic regression. Total observed errors (HCP and technology) were analysed using a negative binomial regression model. Vitalograph Pneumatic Spirometry results were compared using a Mann Whitney U test. <h3>Results</h3> A total of 493 (89.1%) patients (stage 1) and 305 (61.9%) (stage 2) were eligible for the full analysis set. The odds of maintaining inhaler mastery were not significantly different for patients using either inhaler, although achieving inhaler mastery was significantly greater in patients using Spiromax compared with Turbohaler at baseline. A higher, non-significant percentage of patients using Spiromax maintained inhaler mastery (assessed by HCPs). This result was supported by significantly higher odds of maintaining mastery when HCP errors were calibrated using independent video assessment in patients using Spiromax (consented videos available for 243/305 patients [79%]). Maintaining inhaler mastery improved asthma control in both treatment groups and was not significantly different (Table 1). <h3>Conclusions</h3> The proportion of patients achieving inhaler mastery at baseline was significantly greater for Spiromax compared with Turbohaler; no significant difference was found in inhaler mastery at 12 weeks. Patients using Spiromax made significantly fewer errors overall (HCP-observed and HCP- and technology-observed) than patients using Turbohaler. Maintaining inhaler mastery improved asthma control in both treatment groups. Independent video assessment can assist HCPs in evaluating device mastery, and is proposed as the gold standard in such studies.
Problems in Anesthesia for Operations on the Heart
Authors: Leroy D. Vandam, Thomas K. Burnap
Journal: New England Journal of Medicine (1956)

IMPROVEMENTS in anesthetic technics have contributed in large part to the advance of cardiac surgery. On the other hand cardiac surgery has progressed so rapidly in the last decade that anesthesia has been hard pressed to keep abreast of the problems presented. Perhaps because of increased knowledge of the physiology of heart disease and the pharmacology of anesthetic agents, the reported results of anesthesia for cardiac surgery have been relatively good.1 2 3 In this clinic a great deal of surgery is accomplished in poor-risk patients, with excellent results. It is the purpose of this report, however, to review some of the . . .
Surface Markers and Prognostic Factors in Acute Lymphoblastic Leukemia
Authors: Ichiro Tsukimoto, Kwan Y. Wong, Beatrice C. Lampkin
Journal: New England Journal of Medicine (1976)

We investigated the surface markers on lymphoblasts from 37 patients with acute lymphoblastic leukemia. Spontaneous rosette formation with sheep erythrocytes (E rosettes) identified T cells and the presence of surface immunoglobulin identified B cells. Eight patients had T-marker lymphoblasts; 28 had no markers (null lymphoblasts), and one patient had B-marker lymphoblasts. The eight patients with T-marker acute lymphoblastic leukemia had massive leukemic infiltration, frequently a mediastinal mass, and a poor prognosis. The T-marker lymphoblasts had a weak or negative periodic acid-Schiff reaction and a very low antigenic stimulation to allogeneic lymphocytes. The association of T-marker lymphoblasts and some of the conventional poor-risk factors appears to be reliable in predicting a poor prognosis.
Erratum to: Understanding Brassicaceae evolution through ancestral genome reconstruction
Authors: Florent Murat, Alexandra Louis, Florian Maumus, Alex Armero, Richard Cook, Hadi Quesneville, Hugues Roest Crollius, Jerome Salse
Journal: Genome biology (2016)

After the publication of this work [1] an error was noticed in Figure 1. There was an extra blue bar added in panel a in the bottom row far left. The corrected Figure 1 has now been updated in the original article. The publisher apologises for this error.
Amoxapine: neuroleptic as well as antidepressant?
Authors: B M Cohen, P Q Harris, R I Altesman, J O Cole
Journal: American Journal of Psychiatry (1982)

Amoxapine, a new antidepressant, is the N-desmethyl analog of loxapine, a neuroleptic. There have been reports suggesting that amoxapine itself or its metabolites have neuroleptic as well as antidepressant properties. With in vitro studies using a radioreceptor assay for neuroleptics, the authors found that amoxapine--and one of its metabolites in particular (7-hydroxyamoxapine)--have potent neuroleptic-like activity. Furthermore, blood specimens from patients receiving amoxapine showed the presence of neuroleptic activity in the same assay. The authors note the implications of these findings for gauging the benefits and risks of treatment with amoxapine, including the risk of neurologic effects.
Nitroprusside in Myocardial Infarction
Authors: Eugene R. Passamani
Journal: New England Journal of Medicine (1982)

This issue of the Journal includes reports of two clinical trials in patients with acute myocardial infarction,1 , 2 testing the hypothesis that nitroprusside, a vasodilator, will reduce mortality when given during the initial 24 to 48 hours of hospitalization.Nitroprusside has been tested in both animal models and patients with myocardial infarction, with mixed results; investigators have reported improvement, no change, and worsening of ST-segment elevation, an index of ischemia. Very little is known about the effect of nitroprusside on infarct size or long-term outcome after infarction. It is agreed that hemodynamic indexes improve with nitroprusside in patients with myocardial infarction . . .
Sexual Transmission and the Natural History of Human Herpesvirus 8 Infection
Authors: Jeffrey N. Martin, Donald E. Ganem, Dennis H. Osmond, Kimberly A. Page-Shafer, Don Macrae, Dean H. Kedes
Journal: New England Journal of Medicine (1998)

Although human herpesvirus 8 (HHV-8) has been suspected to be the etiologic agent of Kaposi's sarcoma, little is known about its seroprevalence in the population, its modes of transmission, and its natural history.The San Francisco Men's Health Study, begun in 1984, is a study of a population-based sample of men in an area with a high incidence of human immunodeficiency virus (HIV) infection. We studied all 400 men infected at base line with HIV and a sample of 400 uninfected men. Base-line serum samples were assayed for antibodies to HHV-8 latency-associated nuclear antigen (anti-LANA). In addition to the seroprevalence and risk factors for anti-LANA seropositivity, we analyzed the time to the development of Kaposi's sarcoma.Anti-LANA antibodies were found in 223 of 593 men (37.6 percent) who reported any homosexual activity in the previous five years and in none of 195 exclusively heterosexual men. Anti-LANA seropositivity correlated with a history of sexually transmitted diseases and had a linear association with the number of male sexual-intercourse partners. Among the men who were infected with both HIV and HHV-8 at base line, the 10-year probability of Kaposi's sarcoma was 49.6 percent. Base-line anti-LANA seropositivity preceded and was independently associated with subsequent Kaposi's sarcoma, even after adjustment for CD4 cell counts and the number of homosexual partners.The prevalence of HHV-8 infection is high among homosexual men, correlates with the number of homosexual partners, and is temporally and independently associated with Kaposi's sarcoma. These observations are further evidence that HHV-8 has an etiologic role in Kaposi's sarcoma and is sexually transmitted among men.
Effect of Human Leukocyte Interferon on Hepatitis B Virus Infection in Patients with Chronic Active Hepatitis
Authors: Harry B. Greenberg, Richard B. Pollard, Larry I. Lutwick, Peter B. Gregory, William S. Robinson, Thomas C. Merigan
Journal: New England Journal of Medicine (1976)

Four patients with chronic hepatitis B infection and chronic active hepatitis were treated with human leukocyte interferon. Three of them had consistently elevated levels of circulating Dane-particle markers, including Dane-particle-associated DNA polymerase activity, hepatitis B core antigen and Dane-particle-associated DNA. Parenteral interferon administration at a dosage between 6.0 X 103 and 17 x 104 U per kilogram per day was associated with a rapid and reproducible fall in all Dane-particle markers in the three patients. The suppressive effect was transient when the interferon was given for 10 days or less but appeared to be more permanent when administration was prolonged for a month or more. In addition, long-term interferon therapy was associated with a marked fall in hepatitis B surface antigen in two of three patients and a disappearance of e antigen in two of two patients. Interferon may be useful in limiting carrier infectivity or eradicating chronic infection. (N Engl J Med 295:517–522, 1976)
Incidence of early-onset multiple myeloma among families with endometrial carcinoma.
Authors: A. R. Sama, W. Gonsalves, X. Fang, H. T. Lynch, S. Thome
Journal: Journal of Clinical Oncology (2010)

1583 Background: In a recent study, multiple myeloma (MM) was found in excess and at an earlier age in first-degree relatives of endometrial carcinoma (EC) patients. We reviewed the Creighton Hereditary Cancer Center experience of MM and EC pedigrees. Methods: After identifying all probands with MM or EC we examined pedigrees with coincident diagnoses of EC and MM. The diagnosis of EC or MM was primarily verified by review of pathology reports or death certificates. Summary statistics including mean and median ages at diagnosis were calculated. Statistical analysis was used to investigate the null hypothesis of no significant age difference at diagnosis of MM and EC in families with MM, EC, and EC/MM. Results: We could not find a single individual proband with both MM and EC in our database. We found 696 individuals with EC and 126 cases of MM in 586 families. We found 26 cases of EC and 26 cases of MM in 20 families in which both cancers were reported. In contrast to the prior study, there was no significant reduction in age at diagnosis of MM in pedigrees with EC. In fact, in our cohort, there was a trend for later onset of EC in families with coincident EC/MM, another argument against a hereditary predisposition. Conclusions: We found no increase in incidence of early onset myeloma in families with EC. Our data does not support an EC and MM correlation (Zighelboim et al. Gynecol Oncol 2007;105:390–4). Families with either MM or EC Families with both MM and EC Test p value Multiple Mean 65.3 64.69 Two-sample pooled t-test 0.82 myeloma Median 65 65.5 Mann-Whitney-Wilcoxon test 0.7676 Endometrial Mean 51.68 57.92 Two-sample pooled t-test 0.0191 carcinoma Median 51 52 Mann-Whitney-Wilcoxon test 0.0452 No significant financial relationships to disclose.
Case 19-2007
Authors: Benjamin T. Davis, Mark S. Pasternack
Journal: New England Journal of Medicine (2007)

A previously healthy 19-year-old college student was transferred to this hospital with fever, hypotension, and pain in the right elbow and left ankle. Eleven days earlier, sore throat and fatigue had developed, and a diagnosis of infectious mononucleosis was made; 1 week later, corticosteroids were prescribed because of severe pharyngitis. On the day of admission, the patient awoke with severe joint pain. Laboratory studies on admission showed leukocytosis and anemia. The next day, the result of a diagnostic test was reported.
Effects of Inhaled Beclomethasone Dipropionate and Alternate-Day Prednisone on Pituitary-Adrenal Function in Children with Chronic Asthma
Authors: Richard Wyatt, James Waschek, Miles Weinberger, Barry Sherman
Journal: New England Journal of Medicine (1978)

Two corticosteroid regimens, alternate-day prednisone and inhaled beclomethasone dipropionate, have been more acceptable than daily oral corti-costeroids for treatment of chronic asthma. To compare the effect of these regimens on hypothalamic-pituitary-adrenal function, 20 children with asthma were evaluated while receiving 20 to 40 mg of prednisone on alternate mornings or 400 to 800 μg per day of inhaled beclomethasone dipropionate in divided daily doses; seven children requiring only non-corticosteroid medication served as controls. Early-morning serum cortisol concentration, urinary free-cortisol excretion and the 11-desoxycortisol response to metyrapone were decreased to a similar degree among children receiving both corticosteroid regimens in comparison with the control patients and were lowest when alternate-day prednisone and inhaled beclomethasone dipropionate were given together. Thus, inhaled beclomethasone dipropionate appears similar to alternate-day prednisone in its effect on hypothalamic-pituitary-adrenal function when used alone; the effect is additive when the two are used together. (N Engl J Med 299:1387–1392, 1978)
Serum Insulin and Growth Hormone Response Patterns in Monozygotic Twin Siblings of Patients with Juvenile-Onset Diabetes
Authors: Klaus Johansen, J. Stuart Soeldner, Ray E. Gleason, Marise S. Gottlieb, Byung N. Park, Robert L. Kaufmann, Meng H. Tan
Journal: New England Journal of Medicine (1975)

To detect abnormalities in the secretion of insulin and growth hormone in monozygotic twin siblings of patients with juvenile-onset diabetes, their responses during oral, cortisone-primed oral, and intravenous, glucose tolerance tests and intravenous tolbutamide tests were compared to those of matched controls. The twins had higher mean serum insulin levels during all tests, but differences reached statistical significance (P less than 0.02) only in the cortisone-primed test. Growth hormone levels were higher in the twins (P less than 0.04) in the intravenous tolbutamide tolerance test. The frequency of abnormal oral glucose tolerance tests among controls, diabetic monozygotic twins and the offspring of two diabetic parents was also compared. Twins and controls had nearly the same frequency of normal tests; however, the diabetic offspring had a significantly higher (P less than 0.001) prevalence of abnormal tests. These data suggest that magnitudes of environmental and genetic factors operating in monozygotic "pre-diabetic" children of diabetic parents.
Drug-Induced Torsades de Pointes and Genetic Screening
Authors: Amit Noheria
Journal: JAMA Internal Medicine (2016)

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BOLERO-2: Health-related quality-of-life in metastatic breast cancer patients treated with everolimus and exemestane versus exemestane.
Authors: J. Thaddeus Beck, Hope S. Rugo, Howard A. Burris, José Baselga, Shinzaburo Noguchi, Michael Gnant, Kathleen I. Pritchard, Lee Bennett, Jean-Francois Ricci, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2012)

539 Background: BOLERO-2, a phase III study, randomized 724 patients with hormone-receptor–positive metastatic breast cancer, who had recurrence or progression on/after prior nonsteroidal aromatase inhibitor therapy, to everolimus (EVE) plus exemestane (EXE) or EXE and placebo. A preplanned 12-month median time interim analysis demonstrated that EVE+EXE significantly improved progression-free survival (PFS) vs EXE+placebo but that EVE+EXE resulted in a higher rate of grade 3/4 toxicity. Per-protocol patient reported health-related quality-of-life (HRQoL) data are limited; here we report on additional post-hoc analyses of these outcomes. Methods: Using the EORTC–QLQ‑C30 questionnaire, HRQoL was assessed at baseline and every 6 weeks thereafter until progression. The QLQ‑C30 consists of 30 items combined into 15 subscales, including a Global Health Status (GHS) where higher scores (range 0 to 100) indicate better HRQoL. This analysis included a protocol-specified time to definitive deterioration (TTD) analysis at a 5% decrease in QoL relative to baseline, with no subsequent increase above this threshold. We report additional sensitivity analyses using 10-point minimally important difference (MID) decreases in QLQ‑C30 score relative to baseline. Treatment arms were compared using a stratified logrank test and a Cox proportional hazards model adjusted for trial stratum (visceral metastases and previous hormone sensitivity), age, sex, race, baseline score and ECOG performance status, prognostic factors, and treatment history. Results: Baseline QLQ‑C30 GHS scores were not statistically significantly different across treatment groups (64.7 vs 65.3; difference -0.7 [95% CI; -4.3, 3.0]). The median TTD in HRQoL was 7.0 months (95% CI; 5.6, 8.3) for EVE+EXE vs 5.6 (95% CI; 4.2, 7.0) for EXE (P = .0792). Adjusted HR (0.80) approached significance (95% CI; 0.63, 1.02). At the 10-point MID, median TTD for EVE+EXE was 9.7 months (95% CI; 8.3, 11.2) vs 8.4 months (95% CI; 6.3, 12.5) for EXE. Adjusted HR was 0.90 (95% CI; 0.69, 1.18). Conclusions: These additional analyses demonstrate that in addition to significantly improving PFS, EVE+EXE does not compromise HRQoL.
Treatment of Chronic Granulocytic Leukemia with Myleran
Authors: Asuman Unugur, Edward Schulman, William Dameshek
Journal: New England Journal of Medicine (1957)

THE chemotherapeutic agent Myleran has been under investigation for the treatment of leukemia during the past five years. This compound, 1:4 - dimethanesulfonyloxybutane (CH3SO2OCH2CH2CH2CH2OSO2CH3), which was synthesized by Timmis1 in 1950, had an intense inhibitory effect on the growth of the Walker rat carcinoma 256 as well as a depressive influence on the myeloid series both in the rat and in man. Haddow and Timmis1 showed that the main depressant action of Myleran was on circulating neutrophils in rats. This led to its trial . . .