tbuckley/cabot-search huggingface dataset:
Points from Letters: Living it up with Concorde
Authors: K. Heymann
Journal: BMJ (1970)

MEDIBCATOISNALin the Bristol centre" conceals some important facts.Rates marginally better than those described in the document were in- troduced here in September, and proved unacceptable to the deputies.This was mainly because these represented (as far as 90% of the sessions were concerned) only a 5 % increase on previous rates, even though
EFFECT OF RETINOIC ACID IN PSORIASIS, II.
Authors: ANGUS MACDONALD, R. M. H. McMINN, LIONEL FRY
Journal: British Journal of Dermatology (1972)

Summary.— Clinical and histological features and mitotic counts have been studied in the lesions of 11 patients with psoriasis who were treated with topically applied retinoic acid ointment for a period of 3 months. Serial biopsies were taken at monthly intervals from treated lesions in all 11 patients and from lesions treated with the unmedicated ointment base in 9. There was no significant difference between treated and placebo groups regarding any of the parameters studied. Irritant effects of the retinoic acid were prominent in 7 patients. The significance of these results is discussed in the light of the known mechanism of action of retinoic acid.
LDL Increases Inactive Tissue Factor on Vascular Smooth Muscle Cell Surfaces
Authors: Marc S. Penn, Chandrashekhar V. Patel, Mei-Zhen Cui, Paul E. DiCorleto, Guy M. Chisolm
Journal: Circulation (1999)

Background −Tissue factor, which is required for the initiation of the extrinsic coagulation cascade, is known to be upregulated in cells within atherosclerotic lesions, including smooth muscle cells. Tissue factor expression on the smooth muscle cell surface could be of pathological significance as a contributor to plaque growth, thrombus formation, and the acute coronary syndrome after plaque rupture. Methods and Results −In this study, we show that LDL increased tissue factor mRNA and cell surface protein in smooth muscle cells without a marked increase in surface tissue factor activity. Hydrogen peroxide activated tissue factor on the cell surface but did not increase tissue factor mRNA or cell surface protein. Sequentially added LDL and hydrogen peroxide increased mRNA, cell surface protein, and activity; surface activity was greater than that observed with hydrogen peroxide alone. The action of hydrogen peroxide did not involve a regulatory mechanism associated with the cytoplasmic tail of tissue factor because a truncated tissue factor lacking the cytoplasmic tail was activated by hydrogen peroxide. Conclusions −These results suggest a novel 2-step pathway for increased tissue factor activity on smooth muscle cell surfaces in which lipoproteins regulate synthesis of a latent tissue factor and oxidants activate the protein complex.
STUDY OF THE SYSTOLIC PHASE OF THE SEPTAL VENTRICULAR CONTRACTION WITH TISSUE DOPPLER AND ITS CORRELATION WITH MORPHOMETRICS IN SEVERE AORTIC VALVE STENOSIS
Authors: Sergio J. Baratta, Demian Chejtman, Matias Failo, Alejandro Benticuaga Navas, Maria L. Ayerdi, Ariel Costa, Jose Santucci, Augusto Gutierrez, Fabian Ferroni, Alejandro Hita
Journal: Journal of the American College of Cardiology (2014)
Panorama responds to editorial on fMRI for vegetative and minimally conscious states
Authors: F. Walsh, F. Simmonds, G. B. Young, A. M. Owen
Journal: BMJ (2013)

Turner-Stokes and colleagues’ editorial suggests that the Panorama special, The Mind Reader: Unlocking My Voice , did not “clearly distinguish” between patients who live in a vegetative state and those in a minimally conscious state.1 However, the script contained several explanations of these conditions; for example, when referring to one patient undergoing assessment: “Staff here will try to assess whether he is minimally conscious with fragments of understanding or vegetative—with no awareness at all.”

Just by viewing this one hour documentary the authors felt able to discern that both the Canadian patients “said to be in a vegetative state” …
A 34-Year-Old Woman With Persistent Cough and Diarrhea
Authors: Cynthia A. Britton
Journal: JAMA (1986)

<h3>History</h3> A 34-year-old woman was admitted to the hospital with watery diarrhea, pain in the left lower quadrant, and persistent cough. A mild anemia and a leukocytosis with slight shift to the left were the only accompanying abnormal laboratory results. Further history is withheld. A barium enema examination (Fig 1) and a barium esophagram of the upper gastrointestinal tract (Fig 2) were performed. <h3>Diagnosis</h3> Crohn's disease involving the colon with esophageal involvement producing a tracheoesophageal fistula. <h3>Comment</h3> At age 24 years, this woman was first diagnosed as having Crohn's disease after developing rectal fistulas and oral ulcerations, both of which resolved with prednisone and sulfasalazine therapy. Five years later, she complained of cough, dysphagia, and watery diarrhea. Endoscopy revealed erythematous, friable mucosa in the midesophagus, which on biopsy was consistent with Crohn's disease. An increase in the intake of steroids resolved the patient's symptoms. She remained symptom free for five
Computer control of anticoagulant dose.
Authors: P E Rose, M Gilbert
Journal: BMJ (1990)

<h3>Abstract</h3> Anaplastic thyroid cancer (ATC) is one of the most lethal solid tumors, yet there are no effective, long-lasting treatments for ATC patients. Most tumors, including tumors of the endocrine system, exhibit an increased consumption of glucose to fuel cancer progression, and some cancers meet this high glucose requirement by metabolizing glycogen. Our goal was to determine if ATC cells metabolize glycogen and if this could be exploited for treatment. We detected glycogen synthase and glycogen phosphorylase (PYG) isoforms in normal thyroid and thyroid cancer cell lines and patient-derived biopsy samples. Inhibition of PYG using CP-91,149 induced apoptosis in ATC cells but not normal thyroid cells. CP-91,149 decreased NADPH levels and induced reactive oxygen species accumulation. CP-91,149 severely blunted ATC tumor growth <i>in vivo</i>. Our work establishes glycogen metabolism as a novel metabolic process in thyroid cells that presents a unique, oncogenic target that could offer an improved clinical outcome. <h3>Significance</h3> Glycogen metabolism plays an important role in combating reactive oxygen species and apoptosis in anaplastic thyroid cancer. Glycogen phosphorylase was inhibited with small molecule inhibitors that limited cell proliferation <i>in vitro</i> and blunted tumor growth in a nude mouse xenograft. This study demonstrates that glycogen metabolism is a viable target in one of the most lethal solid tumors.
Changes recommended in use of human diploid cell rabies vaccine
Authors: Charles Marwick
Journal: JAMA (1985)

In June 1980, a new rabies vaccine, using a virus cultivated on human cells, was licensed. Now, five years later, some changes have been recommended in how it is used. At the time of its licensing at the beginning of the decade, the new vaccine was hailed as a major advance. This opinion was based principally on the heightened immunogenicity of the vaccine, which made it possible to reduce the number of doses for both pre-exposure prophylaxis and post-exposure treatment, compared with the then-available rabies vaccine. The latter employed virus cultivated on duck embryo tissues. Since then, about 400,000 doses of the newer human diploid cell vaccine have been given to about 100,000 persons in the United States, according to the Centers for Disease Control in Atlanta. But recently, a problem with the new vaccine has emerged. Hypersensitivity reactions have been reported in some individuals, mostly among those given routine
Properties of human asialo-factor VIII. A ristocetin-independent platelet-aggregating agent.
Authors: L De Marco, S S Shapiro
Journal: Journal of Clinical Investigation (1981)

Human Factor VIII desialylated by treatment with Vibrio cholerae neuraminidase (ASVIII) aggregated human platelets in the absence of ristocetin in platelet-rich plasma and, to a lesser extent, in washed platelet suspensions. Aggregation is accompanied by thromboxane formation and is completely inhibited by EDTA. Aspirin blocks the second phase of aggregation and abolishes thromboxane production. Subaggregating doses of ASVIII and of either ADP, epinephrine, or collagen produce prompt and complete platelet aggregation. Bernard-Soulier syndrome platelets either did not aggregate with ASVIII (Two cases) or showed markedly decreased aggregation (one cases). Factor VIII complex was prepared from the plasma of two patients with variant von Willebrand's disease (sialic acid content 142 and 75 nmol/mg, respectively); neither protein generated platelet-aggregating activity upon desialylation. [3H]ASVIII binds rapidly to platelets and 37 degrees C, while tritiated, fully sialylated factor VIII binds to a negligible extent. As little as 1--2 micrograms ASVIII bound/10(9) platelets is capable of inducing platelet aggregation. ASVIII may be a useful tool for investigating platelet-Factor VIII interactions in the absence of ristocetin. Furthermore, desialylated Factor VIII might play a physiologic role in Factor VIII-mediated platelet reactions in vivo.
A Population-Based Study of Appetite-Suppressant Drugs and the Risk of Cardiac-Valve Regurgitation
Authors: Hershel Jick, Catherine Vasilakis, Larry A. Weinrauch, Christoph R. Meier, Susan S. Jick, Laura E. Derby
Journal: New England Journal of Medicine (1998)

Recent case reports suggest that a combination of the appetite suppressants fenfluramine and phentermine is associated with an increased risk of cardiac-valve regurgitation. There are also reports of valvular disorders in persons taking fenfluramine or dexfenfluramine alone, particularly for more than three months.
Malignant Testicular Tumors in Brothers
Authors: Adolph M. Hutter
Journal: JAMA (1967)

TESTICULAR TUMORS are uncommon, comprising 0.7% of all malignant neoplasms in males in one large survey.1The majority are found in men 20 to 40 years of age. The highest incidence occurs between the ages of 29 and 34 years during which period they are the most common malignant tumor in males.2  Malignant testicular tumors occurring in brothers have been reported in only five sets of twins and three sets of nontwins. In addition, the rare tumor, gonadoblastoma, has been reported in 6-year-old monozygous twins with a pure gonadal dysgenesis who were phenotypically female but who had a 44 A-XY karyotype.3  Champlin4in 1930 reported the first cases of testicular tumors in twins. He described identical twins, one of whom developed a sarcoma of the right testicle seven years before his brother developed an embryonal carcinoma—so called round cell sarcoma, also of the right testicle. Domrich
Radiation Therapy of Early Prostatic Cancer
Authors: John P. Storaasli
Journal: JAMA (1961)

The usual palliative treatment of inoperable carcinoma of the prostate results in an average survival of 2.5 years. To improve this, new approaches to therapy were explored by the authors. This monograph deals with the treatment of prostatic carcinoma with radioactive colloidal gold. The cases that mainly concerned the authors were those in which the cancer had spread beyond the prostate gland. While surgery is the main, and irradiation only the occasional, method of therapy, it is suggested that a combination of the two may give the best results. This should particularly apply to interstitial irradiation with radioactive gold and surgery. The details of the authors' technique are well presented. From the clinical material, it was discovered that the group of patients with early prostatic cancers fall into two categories, namely, those with and those without lymph node involvement. Ten per cent of the radioactivity was detected in uninvolved lymph
On a Nonparametric Combination Method for Dependent Permutation Tests with Applications
Authors: Fortunato Pesarin
Journal: Psychotherapy and Psychosomatics (1990)

This paper deals with a combination method for dependent permutation tests, which is nonparametric with respect to the underlying unknown dependence structure. The method is based on a simulation or resampling procedure, conditional on the data, which provides a simulated estimate of the permutation distribution of any statistic. Applications to some unusual and quite complex testing problems are shown.
Are isolated maternity units run by general practitioners dangerous?
Authors: G Young
Journal: BMJ (1987)

A retrospective survey was carried out of women admitted in labour to an isolated maternity unit run by general practitioners in Penrith. In the five years 1980-4, 1267 women began labour in Penrith, of whom 1153 (91%) never required help from a consultant unit. Ninety required transfer during labour. Ten mothers and four neonates required transfer during the early puerperium, all to one receiving unit in Carlisle. There were six perinatal deaths during the five years; five occurred in babies delivered after transfer. The perinatal mortality was 4.7/1000. The low mortality, the low level of intervention, and the preference of women all support the retention of isolated units.
Effect of Race on the Presentation and Management of Patients with Acute Chest Pain
Authors: Paula A. Johnson
Journal: Annals of Internal Medicine (1993)

Objective: To compare racial differences in clinical presentation, natural history, and access to medical care and procedures among emergency-department patients with acute chest pain. Design: Prospective follow-up study of consecutive patients coming to the emergency department because of acute chest pain. Setting: Two university medical centers. Patients: A total of 3031 patients who were 30 years or older and who came to the emergency department with acute chest pain from 1984 to 1986. Main Results: African-Americans tended to have slightly, but not always significantly, lower rates of acute myocardial infarction, acute ischemic heart disease, and major complications, after adjusting for presenting symptoms and signs; the adjusted odds ratios for African-Americans were as follows: 0.77 (95% CI, 0.54 to 1.1) for acute myocardial infarction, 0.75 (CI, 0.59 to 0.95) for ischemic heart disease, and 0.79 (CI, 0.45 to 1.4) for death or major complications. Clinical factors classically associated with acute myocardial infarction were equally predictive in African-Americans and whites. After adjustments were made for multiple clinical factors, a lower proportion of African-Americans were admitted to the hospital (odds ratio, 0.69; CI, 0.56 to 0.84), and, once admitted, were somewhat less likely to be triaged to the coronary care unit (odds ratio, 0.81; CI, 0.65 to 1.0). In adjusted analyses, African-Americans were as likely to undergo cardiac catheterization as whites (odds ratio, 0.86; CI, 0.64 to 1.2) but were less likely to undergo coronary artery bypass procedures once severity of coronary disease was included in the analysis (odds ratio, 0.24; CI, 0.08 to 0.71). Conclusion: African-Americans and whites had a similar presentation and natural history of acute myocardial infarction and, after adjusting for probability of clinical events, similar access to most medical care and cardiac procedures. However, the rate of coronary artery bypass procedures was much lower among African-Americans than among whites. Reasons for this difference should be studied.
The Ventilatory Response to Acute Base Deficit in Humans
Authors: NATHANIEL F. PIERCE
Journal: Annals of Internal Medicine (1970)

The time courses of ventilatory response to the development and correction of acute base-deficit acidosis were studied in 35 patients with cholera. In normal controls and during stable base deficit the steady-state relation between arterial PCO2 and [HCO-3]a was highly predictable. After both rapid development of base deficit (when mean [HCO-3]a fell 13 mEq/liter in 14 hr) and rapid correction (when mean [HCO-3]a increased 9 mEq/liter in 3 hr), ventilatory response lagged behind the change in [HCO-3]a and pHa. This resulted in a significant deviation of observed arterial PCO2 from the expected steady-state values. The magnitude of this deviation was influenced by both the magnitude and duration of change in [HCO-3]a. When [HCO-3]a remained stable, after either rapid development or correction of base deficit, ventilatory response reached steady-state level within 11 to 24 hr. When [HCO-3]a fell slowly (mean fall of 4 mEq/liter in 15 hr) or rose slowly (mean rise of 6 mEq/liter in 24 hr), a lag in ventilatory response was not demonstrable. The time courses of ventilatory response to both base loss and replacement were similar when both magnitude and duration of change in [HCO-3]a were considered.
Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1–risk myelodysplastic syndromes with karyotypes other than deletion 5q
Authors: Azra Raza, James A. Reeves, Eric J. Feldman, Gordon W. Dewald, John M. Bennett, H. Joachim Deeg, Luke Dreisbach, Charles A. Schiffer, Richard M. Stone, Peter L. Greenberg, Peter T. Curtin, Virginia M. Klimek, Jamile M. Shammo, Deborah Thomas, Robert D. Knight, Michele Schmidt, Kenton Wride, Jerome B. Zeldis, Alan F. List
Journal: Blood (2007)
A Phase I Monotherapy Study of RG7212, a First-in-Class Monoclonal Antibody Targeting TWEAK Signaling in Patients with Advanced Cancers
Authors: Ulrik N. Lassen, Didier Meulendijks, Lilian L. Siu, Vaios Karanikas, Morten Mau-Sorensen, Jan H.M. Schellens, Derek J. Jonker, Aaron R. Hansen, Mary E. Simcox, Kathleen J. Schostack, Dean Bottino, Hua Zhong, Markus Roessler, Suzana M. Vega-Harring, Tiantom Jarutat, David Geho, Ka Wang, Mark DeMario, Glenwood D. Goss
Journal: Clinical Cancer Research (2014)

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible molecule 14 (Fn14) are a ligand-receptor pair frequently overexpressed in solid tumors.Fn14 signaling regulates multiple oncogenic processes through MAPK, AKT, and NFκB pathway activation. A phase I study of RG7212, a humanized anti-TWEAK IgG1κ monoclonal antibody, was conducted in patients with advanced solid tumors expressing Fn14.Dose escalations, over a 200- to 7,200-mg range, were performed with patients enrolled in weekly (QW), bi-weekly (Q2W), or every-three-week (Q3W) schedules. Primary objectives included determination of dose and safety profile. Secondary endpoints included assessments related to inhibition ofFn14 signaling, tumor proliferation, tumor immune cell infiltration, and pharmacokinetics.In 192 treatment cycles administered to 54 patients, RG7212 was well-tolerated with no dose-limiting toxicities observed. More than 95% of related adverse events were limited to grade 1/2. Pharmacokinetics were dose proportional for all cohorts, with a t1/2 of 11 to 12 days. Pharmacodynamic changes included clearance of free and total TWEAK ligand and reductions in tumor Ki-67 and TRAF1. A patient with BRAF wild-type melanoma who received 36 weeks of RG7212 therapy had tumor regression and pharmacodynamic changes consistent with antitumor effects. Fifteen patients (28%) received 16 or more weeks of RG7212 treatment.RG7212 demonstrated excellent tolerability and favorable pharmacokinetics. Pharmacodynamic endpoints were consistent with reducedFn14 signaling. Tumor regression was observed and prolonged stable disease was demonstrated in multiple heavily pretreated patients with solid tumors. These encouraging results support further study of RG7212. Clin Cancer Res; 21(2); 258-66. ©2014 AACR.
Calmodulin is a subunit of nitric oxide synthase from macrophages.
Authors: H J Cho, Q W Xie, J Calaycay, R A Mumford, K M Swiderek, T D Lee, C Nathan
Journal: The Journal of Experimental Medicine (1992)

A central issue in nitric oxide (NO) research is to understand how NO can act in some settings as a servoregulator and in others as a cytotoxin. To answer this, we have sought a molecular basis for the differential regulation of the two known types of NO synthase (NOS). Constitutive NOS's in endothelium and neurons are activated by agonist-induced elevation of Ca2+ and resultant binding of calmodulin (CaM). In contrast, NOS in macrophages does not require added Ca2+ or CaM, but is regulated instead by transcription. We show here that macrophage NOS contains, as a tightly bound subunit, a molecule with the immunologic reactivity, high performance liquid chromatography retention time, tryptic map, partial amino acid sequence, and exact molecular mass of CaM. In contrast to most CaM-dependent enzymes, macrophage NOS binds CaM tightly without a requirement for elevated Ca2+. This may explain why NOS that is independent of Ca2+ and elevated CaM appears to be activated simply by being synthesized.
First do no harm
Authors: F. Godlee
Journal: BMJ (2013)

Most countries in the world have heeded the World Health Organization’s call to include hepatitis B vaccine in childhood immunisation programmes. But six countries in Northern Europe, including the United Kingdom, have not. Why are they holding out? Hepatitis B infects two billion people worldwide, causing hundreds of millions of chronic infections and early deaths from liver disease. About 14 million people in Europe are chronically infected.

Such high numbers help Pierre Van Damme and colleagues make a good case for the remaining six European countries to fall into line (doi:10.1136/bmj.f4057). The alternative approaches—targeting people at high risk and preventing perinatal transmission—are …
Antiviral Autophagy Restricts Rift Valley Fever Virus Infection and Is Conserved from Flies to Mammals
Authors: Ryan H. Moy, Beth Gold, Jerome M. Molleston, Veronica Schad, Kilangsungla Yanger, Mary-Virginia Salzano, Yoshimasa Yagi, Katherine A. Fitzgerald, Ben Z. Stanger, Samantha S. Soldan, Sara Cherry
Journal: Immunity (2014)
Right atrial myxoma: unusual clinical presentation and atypical glandular histology.
Authors: W Frishman, S Factor, A Jordan, C Hellman, U Elkayam, T LeJemtel, J Strom, H Unschuld, R Becker
Journal: Circulation (1979)

A 57-year-old black female presented with a 1-month of right-sided congestive heart failure and clinical evidence of pulmonic and tricuspid valvular stenosis and insufficiency. The echocardiographic examination and ventriculography demonstrated a large right atrial tumor interfering with the function of both right-sided valves. The patient underwent successful surgical resection of the tumor. Histologically, the tumor had cellular areas typical of myxoma, as well as glandular areas, a feature which has been described very rarely in this lesion. Electron microscopy of the glandular zones, which has never been reported previously, shown cells having essential homology with the usual myxoma elements. The atypical histopathology of this lesion supports the theory that atrial myxomas are true neoplasms, and are not derived from unusually organized mural thrombi.