tbuckley/cabot-search huggingface dataset:
PLASMA LIPOPROTEIN METABOLISM IN PERFUSED RAT LIVERS. II. TRANSFER OF FREE AND ESTERIFIED CHOLESTEROL INTO THE PLASMA*
Authors: Paul S. Roheim, David E. Haft, Lewis I. Gidez, Abraham White, Howard A. Eder
Journal: Journal of Clinical Investigation (1963)

In a previous paper (1), the synthesis and entry into the plasma of the protein moiety of the different lipoprotein classes has been described.The present studies deal with the metabolism of the free and esterified cholesterol of the lipoproteins.Relatively little is known of the metabolism of the plasma lipids as they exist in the various lipo- protein fractions.Study of certain lipids is diffi- cult, if not impossible, because exchange occurs among different lipoprotein fractions, and useful observations can be made only with those lipids not undergoing exchange (2).Previous studies (3-5) have shown that the in vitro exchange of ester cholesterol is slow relative to that of free cholesterol.In the present study, we labeled free and esterified cholesterol of the plasma biosynthetically and measured their equilibration be- tween various lipoprotein fractions.After we established that there was virtually no exchange of esterified cholesterol in vitro, we examined the metabolism of this lipid fraction of the various lipoproteins. METHODSAnimals.Male rats of the Wistar strain 1 weighing 300 to 500 g were used as blood and liver donors in all studies except the two shown in Tables VI, VII, and VIII, in which Sprague-Dawley rats 2 were used.The standard diet was one of Rockland Farm mouse pellets.
Relative Value of Inflammatory, Hemostatic, and Rheological Factors for Incident Myocardial Infarction and Stroke
Authors: Ioanna Tzoulaki, Gordon D. Murray, Amanda J. Lee, Ann Rumley, Gordon D.O. Lowe, F. Gerald R. Fowkes
Journal: Circulation (2007)

Background— The aim of our present study was to compare the association of a wide range of 17 biomarkers of inflammation, hemostasis, and blood rheology with incident heart disease and stroke after accounting for an indicator of subclinical atherosclerotic disease and traditional risk factors and also to determine their incremental predictive ability. Methods and Results— We used data from the Edinburgh Artery Study, a population cohort study started in 1987 that comprised 1592 men and women aged 55 to 74 years. Subjects were followed for a mean of 17 years, and 416 of them suffered at least 1 cardiovascular event. In analyses adjusted for cardiovascular risk factors and history of cardiovascular disease (CVD): C-reactive protein, interleukin-6, fibrinogen, fibrin D-dimer, tissue plasminogen activator (t-PA), leukocyte elastase, and lipoprotein(a) (all P &lt;0.01), as well as von Willebrand factor and plasma viscosity (both P &lt;0.05), had significant hazard ratios for incident CVD. Further adjustment for a measure of subclinical atherosclerosis (ankle brachial index) had little impact on these associations. The hazard ratios (95% CI) for incident CVD between top and bottom tertiles in the latter analysis were 1.78 (1.30 to 2.45) for C-reactive protein, 1.85 (1.33 to 2.58) for interleukin-6, and 1.76 (1.35 to 2.31) for fibrinogen. Single biomarkers provided little additional discrimination of incident CVD to that obtained from cardiovascular risk factors and the ankle brachial index. An incremental score of multiple markers [interleukin-6, t-PA, intercellular adhesion molecule 1, and lipoprotein(a)] provided some added discrimination. Conclusions— Several “novel” risk factors predicted CVD after adjustments for conventional risk factors and also for a measure of asymptomatic disease. However, their incremental predictive ability was modest and their clinical utility remains uncertain.
Decreases in human dendritic cell–dependent TH2-like responses after acute in vivo IgE neutralization
Authors: John T. Schroeder, Anja P. Bieneman, Kristin L. Chichester, Robert G. Hamilton, HuiQing Xiao, Sarbjit S. Saini, Mark C. Liu
Journal: Journal of Allergy and Clinical Immunology (2010)
Changing perspectives on the genetic effects of radiation
Authors: C. C. Li
Journal: JAMA (1963)

This little book is the text of the Beaumont Lecture delivered by Dr. Neel to the Medical Society of Wayne County, Michigan. It is both desirable and timely to have one of the most controversial subjects in radiobiology discussed with a group of physicians, because medicine, like industry, must continue to utilize ionizing radiation in its profession. Dr. Neel, with his vast experience in studies of Hiroshima and Nagasaki, is particularly qualified to review this subject. Neel's main thesis is that evaluation and decision concerning exposure to radiation should be based not only on the balance between beneficial and deleterious effects of radiation alone, but on a broader frame, since radiation is only one of a number of other dysgenic agents introduced into our modern environment. As to the problem of fall-out from bomb tests, he says (p 76): "I am a firm believer in the control of atomic weapons,
P149 Effect of macitentan on pulmonary arterial hypertension-related hospitalisations: results from the randomised controlled SERAPHIN trial: Abstract P149 Table 1.
Authors: G Coghlan, RN Channick, LJ Rubin, N Galiè, L Perchenet, G Simonneau
Journal: Thorax (2013)

<h3>Introduction and objectives</h3> Macitentan, a novel dual endothelin receptor antagonist with sustained receptor binding, significantly reduced the risk of morbidity and mortality in pulmonary arterial hypertension (PAH) patients in the SERAPHIN trial (NCT00660179), the first event-driven outcomes trial in PAH. The effect of macitentan on the risk of PAH-related hospitalisation was evaluated in this study. <h3>Methods</h3> In SERAPHIN, a multicentre, double-blind, placebo-controlled trial in PAH, patients (aged =12 years) in WHO functional class II–IV were randomised (1:1:1) to oral macitentan 3mg, 10mg, or placebo once-daily. Time to death due to PAH or hospitalisation for PAH up to end of treatment (EOT), and time to hospitalisation for PAH up to EOT were evaluated (Kaplan–Meier analysis). Treatments were compared using log-rank tests. Annual rates of PAH-related hospitalisations and inpatient hospital days up to EOT were also assessed. <h3>Results</h3> For the 742 patients randomised, the median treatment duration was &gt;2 years. The risk of death due to PAH or hospitalisation for PAH was reduced vs placebo by 33% (97.5% CL: 3–54%; P = 0.0146) in the macitentan 3mg group and 50% (97.5% CL: 25–67%; P &lt; 0.0001) in the macitentan 10mg group. Risk of hospitalisation for PAH was reduced by 39% (97.5% CL: 10–58%; P = 0.0040) with macitentan 3mg and 50% (97.5% CL: 24–66%; P = 0.0001) with macitentan 10mg. Overall, 33% (n = 82), 23% (n = 58), and 20% (n = 49) of patients randomised to placebo, macitentan 3mg, and macitentan 10mg, respectively, were hospitalised at least once for PAH. Compared with placebo, the rate of PAH-related hospitalisations and number of inpatient hospital days per year were reduced by 43% (P = 0.0068) and 33% (P = 0.2707), respectively, with macitentan 3mg, and by 55% (P = 0.0002) and 52% (P = 0.0416), respectively, with macitentan 10mg (Table). Macitentan was well tolerated, with similar incidences of elevated liver aminotransferases and peripheral oedema across groups. Adverse events more frequently associated with macitentan vs placebo were headache, nasopharyngitis, and anaemia. <h3>Conclusions</h3> Macitentan significantly reduced the risk of hospitalisation for PAH and the number of PAH-related hospitalisations and inpatient days (10mg only). These data offer further evidence that macitentan has beneficial effects on long-term outcomes in PAH.
An Address ON MIND AND MOTIVE: SOME NOTES ON CRIMINAL LUNACY: Delivered before the Section of Forensic Medicine of the Seventeenth International Congress of Medicine
Authors: D. Nicolson
Journal: BMJ (1913)

<b>1469</b> <b>Objectives: </b>We have previously demonstrated that low concentrations (0.1 mg/ml) of 2-Deoxyglucose (2-DG) have significant therapeutic effects on a variety of human cancer cell lines. In order to understand the mechanisms underlying the effects of 2-DG we evaluated in-vitro exogenous glucose utilization and cellular proliferation during 2-DG treatment. <b>Methods: </b>Two NSCLC cell lines (H3255 and HCC4006) with different degrees of sensitivity to 2-DG treatment were studied. To measure the effects of 2-DG treatment on glucose utilization and cellular proliferation, 1 x 105 cells were plated in media with 2 mg/ml glucose and uptakes of F18-fluorodeoxyglucose (FDG) and F18-fluorothymidine (FLT) were measured before and after treatment with 0.1 mg/ml 2-DG for three days. 2-DG was not present during the FDG/FLT uptake experiments. The intracellular radiotracer concentration was calculated by dividing the total sample FDG or FLT uptake by the total cellular volume, which was determined by measurements of cell diameters and total cell number with a Beckman Coulter Counter. The degree of growth inhibition was measured by counting the number viable, trypan blue negative treated cells, relative to controls. <b>Results: </b>As expected from previous experiments, 2-DG treatment was more effective in HCC4006 than in H3255 cells (reduction in the number of viable cells 50% vs. 35%, respectively). This corresponded to an approximately 2-times higher baseline FDG-uptake in HCC4006 as compared to H3255 cells. However, 2-DG treatment had only a minor impact on FDG-uptake. Treatment with 0.1 mg/ml 2-DG for 3 days reduced FDG uptake by 14% in HCC4006 (p=NS) and by 24% in H3225 (p=NS). In contrast, 2-DG treatment markedly reduced FLT uptake by 49% in HCC4006 (p&lt;0.001) and by 22% in H3255 (p=0.05). <b>Conclusions: </b>These results imply that in cells with a high baseline FDG uptake, 2-DG at a low concentration (1/10th of the normal plasma concentration) that only minimally inhibits glucose metabolism significantly inhibits cellular proliferation. These findings warrant further testing of 2-DG treatment in tumor models with high glycolytic activity.
P2-194: Induction chemotherapy (CT) and concomitant chemo-radiotherapy (CT-RT) with vinorelbine oral (NVBo) plus cisplatin (CDDP) in stage III Non-Small Cell Lung Cancer (NSCLC): final results of an international Phase II trial
Authors: Maciej J. Krzakowski, Mariano Provencio, Beata Utracka-Hutka, Eugenio Villa, Manuel Codes, Abraham Kuten, Bernard Dubray
Journal: Journal of Thoracic Oncology (2007)
Continuity of Outpatient Care in Elderly Men
Authors: Stephen P. Flynn
Journal: JAMA (1985)

To the Editor.—  I read with interest the study by Wasson et al 1 about continuity of care. The study was a thorough and comprehensive attempt to demonstrate the effect of continuity on many health care outcomes.  Interestingly, most of the outcomes studied showed no significant differences between the continuous and discontinuous groups. In addition to patient satisfaction, the major difference was in the length of hospitalization, although the number of hospital admissions was similar for both groups. The reasons for the longer stays are unclear, but if discontinuous care was responsible, this would have significant economic implications. However, since continuity did not appear to affect other process outcomes (preventive measures, appointment-keeping behavior, or use of medications), I find it difficult to understand the association between continuous care and the decreased length of hospital stays.  Even if this association were to prove causative, it is interesting to note the level of
Emerging roles of vasoactive intestinal peptide: a new approach for autoimmune therapy
Authors: E. Gonzalez-Rey, P. Anderson, M. Delgado
Journal: Annals of the Rheumatic Diseases (2007)

Identification of the factors that regulate the immune tolerance and control the appearance of exacerbated inflammatory conditions is crucial for the development of new therapies of autoimmune diseases. Some neuropeptides and hormones have emerged as endogenous agents that participate in the regulation of the processes that ensure self-tolerance. Among them, the vasoactive intestinal peptide (VIP), a well-characterised endogenous anti-inflammatory neuropeptide, has shown therapeutic potential for a variety of immune disorders. Here we examine the latest research findings, which indicate that VIP participates in maintaining immune tolerance in two distinct ways: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T cell effectors.
A FATAL CASE OF PUERPERAL CONVULSIONS
Authors: G. Pound
Journal: BMJ (1854)

I AM induced, by reading the valuable and imtructive papers which have been lately published in the AssocIATION JOURNAL, on the subject of puerper cn sions, to send the particulars, as far as I recollect them, of a fatal case which occurred in my practice two years ago.'CAM.I was called on the night of the 23rd August 1852 to M. B., a young unmarried girl of seventeen; her father, who fetched me, stated that his daughter was very ill, and "that they could make nothing of her".I went immedi-
Recombinant tissue-type plasminogen activator in canine embolic pulmonary hypertension. Effects of bolus versus short-term administration on dynamics of thrombolysis and on pulmonary vascular pressure-flow characteristics.
Authors: R M Prewitt, F Shiffman, D Greenberg, R Cook, J Ducas
Journal: Circulation (1989)

We used a canine model of embolic pulmonary hypertension, induced by injection of autologous radioactive blood clots, to investigate effects of recombinant tissue-type plasminogen activator (rt-PA) on dynamics of thrombolysis and on pulmonary pressure-flow (PQ) characteristics. Over 5 (rt-PA5) or 15 (rt-PA15) minutes, 1 mg/kg rt-PA was infused. Rate and extent of thrombolysis were assessed by counting over both lung fields with a gamma camera. Emboli increased mean pulmonary artery pressure from 14 to 36 mm Hg (p less than 0.005). This change was predominantly due to an increase in the effective outflow pressure (PI) (from 9 to 29 mm Hg, p less than 0.001), obtained by extrapolation from the linear PQ relation. While pulmonary hemodynamics improved with rt-PA5 and rt-PA15, the change was greatest with rt-PA15. For example, the increase in PI that occurred with embolization was abolished with rt-PA15. Also, the decrease in pulmonary artery pressure was greatest with rt-PA15. While not significantly different, extent of total clot lysis tended to be greatest with rt-PA15 (p less than 0.07). Also, while during infusion, the concentration of rt-PA5 was threefold that of rt-PA15, the corresponding rate of thrombolysis was similar with rt-PA5 and rt-PA15. These results indicate that the improvement in pulmonary hemodynamics with rt-PA is primarily explained by a decrease in PI. Furthermore, they suggest an upper limit to the dose-thrombolytic rate relation with rt-PA.
Wimps can blame their genes
Authors: D. Josefson
Journal: BMJ (1999)

Anecdotal evidence has shown that people vary greatly in their sensitivity to pain and in their response to analgesics. Now, new research indicates that there is a genetic basis for differences in pain perception. The findings may lead to a more tailored approach towards determining doses of analgesic and to a better understanding of opiate addiction.

Working with mouse models, scientists from Johns Hopkins University in Baltimore and the National Institute of Drug Abuse in …
Evaluation of safety and clinical efficacy of higher dose immunotherapy with AIC (immunostimulatory DNA conjugated with Amb a 1) in patients with ragweed-induced seasonal allergic rhinitis (SAR)
Authors: A.R. Vaishnav, S.B. Whaley, R. Hamilton, D. Levitt, P.S. Creticos
Journal: Journal of Allergy and Clinical Immunology (2005)
Control and Direction of Allied Health Education
Authors: Colin R. Macpherson
Journal: JAMA (1971)

In discussing the appropriate roles of the different groups outlined in the subtitle of this communication, it is probably not necessary to state that the only roles they have in common are those of educating the students and cooperating with each other. There is every reason to hope that in diversity may lie strength. Traditionally, the hospital program has been the most common, and often, virtually the only type of program that was available. It has become obvious that, with the diversity of programs and with the increasing sophistication of education needed in each of the allied health fields, the hospital can no longer maintain this dominant role. One result has been the development of university programs, particularly of programs in schools of allied health. This has, in turn, made it possible to educate more students more effectively and at a lower unit cost than that which the hospital has
Use of Benzedrine Sulphate by Psychopaths
Authors: H. J. Shorvon
Journal: BMJ (1945)

Benzedrine (amphetamine) sulphate was first introduced in America in 1935 by Prinzmetal and Bloomberg for the treat- ment of narcolepsy.Guttmann in 1936 reported its use in this country in cases of depression, and in collaboration with Sargant described its psycholbgical effects in 1937.Since then an enormous literature has accumulated on its pharmacological and physiological action and its therapeutic application in narcolepsy, post-encephalitic Parkinsonism, alcoholism, epilepsy, obesity, etc.Its use in psychopathic states and behaviour dis- orders, both in adults and in children, has been described by Cutts and Jasper (1939), Bradley and Bowen (1941), and Korey (1944), and, on a larger scale in connexion with electro- encephalographic studies, by Denis Hill (personal communica- tion).The beneficial effects of benzedripe in certain types of psychopathy have been observed in numerous instances by my colleagues at the Sutton Emergency Hospital.Hill, as quoted by Sargant and Slater (1944), has noted that certain psychopaths can tolerate benzedrine in enormous doses and benefit from the therapy, as opposed to normal persons, who are intolerant of high doses.The case here recorded illustrates this point.
Randomized Phase II Study of Cisplatin With Gemcitabine or Paclitaxel or Vinorelbine as Induction Chemotherapy Followed by Concomitant Chemoradiotherapy for Stage IIIB Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Study 9431
Authors: Everett E. Vokes, James E. Herndon, Jeffrey Crawford, Kenneth A. Leopold, Michael C. Perry, Antonius A. Miller, Mark R. Green
Journal: Journal of Clinical Oncology (2002)

To evaluate new drugs in combination with cisplatin in unresectable stage III non-small-cell lung cancer, Cancer and Leukemia Group B (CALGB) conducted a randomized phase II study of two cycles of induction chemotherapy followed by two additional cycles of the same drugs with concomitant radiotherapy.Eligible patients received four cycles of cisplatin at 80 mg/m(2) on days 1, 22, 43, and 64 with arm 1: gemcitabine 1,250 mg/m(2) on days 1, 8, 22, and 29 and 600 mg/m(2) on days 43, 50, 64, and 71; arm 2: paclitaxel 225 mg/m(2) for 3 hours on days 1 and 22 and 135 mg/m(2) on days 43 and 64; and arm 3: vinorelbine 25 mg/m(2) on days 1, 8, 15, 22, and 29 and 15 mg/m(2) on days 43, 50, 64, and 71. Radiotherapy was initiated on day 43 at 2 Gy/d (total dose, 66 Gy).One hundred seventy-five eligible patients were analyzed. Toxicities during induction chemotherapy consisted primarily of grade 3 or 4 granulocytopenia. Grade 3 or 4 toxicities during concomitant chemoradiotherapy consisted of thrombocytopenia, granulo-cytopenia, and esophagitis. Response rates after completion of radiotherapy were 74%, 67%, and 73% for arms 1, 2, and 3, respectively. Median survival for all patients was 17 months. One-, 2-, and 3-year survival rates for the patients on the three arms were 68%/37%/28%, 62%/29%/19%, and 65%/40%/23%.Four cycles of gemcitabine, vinorelbine, or paclitaxel in combination with cisplatin can be administered at these doses and schedules. The observed survival rates exceed those of previous CALGB trials and may be attributable to the use of concomitant chemoradiotherapy. Induction chemotherapy added to concomitant chemoradiotherapy is being evaluated in a phase III randomized trial.
A Clinical Trial of Change in Maternal Smoking and Its Effect on Birth Weight
Authors: Mary Sexton
Journal: JAMA (1984)

These clinical trial results are the first, to our knowledge, from a prospective, randomized, and controlled experiment demonstrating that a reduction of smoking during pregnancy improves the birth weight of the infant. Nine hundred thirty-five pregnant smokers were randomly assigned to treatment and control groups; the former received smoking intervention. At the eighth month of pregnancy, differences between the two groups in salivary thiocyanate level and reported smoking were statistically significant. For single, live births, the treatment group infants had a mean birth weight that was 92 g heavier and were 0.6 cm greater in length than the control group infants. The decrement in weight related to smoking cannot be fully explained by gestational age. The findings suggest that some fetal growth retardation can be overcome by the provision of antismoking assistance to pregnant women. (<i>JAMA</i>1984;251:911-915)
Child Abuse
Authors: Ann S. Botash
Journal: JAMA (2001)

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Pursuit of 'Eucardia'
Authors: Samuel Vaisrub
Journal: JAMA (1978)

Increased heart rate and blood pressure, the invariable accompaniments of physical exercise, are also characteristic of acute anxiety. In the latter, however, these changes are rarely pleasurable. No book on acute anxiety has competed with Running for a best-seller status. Moreover, no cardiac benefits, ascribed to the hemodynamic aspects of exercise, have been claimed for anxiety. Even the mechanism of the tachycardia of anxiety differs from that of exercise. In the latter, vagal withdrawal may play a greater part than sympathetic overactivity. 1 β-Adrenergic blocking agents, which reduce the heart rate in emotional stress, are generally ineffective in exercise.  The usefulness of β-adrenergic blocking drugs, particularly oxprenolol hydrochloride, has been demonstrated in a number of acutely stressful activities, such as public speaking, driving in heavy traffic, race-car driving, or landing an airplane. Monitored heart rates and, whenever practicable, blood pressures showed a substantial increase during these activities. Oxprenolol hydrochloride in