tbuckley/cabot-search huggingface dataset:
Clinical Loyalties and the Social Purposes of Medicine
Authors: M. Gregg Bloche
Journal: JAMA (1999)

Physicians increasingly face conflicts between the ethic of undivided loyalty to patients and pressure to use clinical methods and judgment for social purposes and on behalf of third parties. The principal legal and ethical paradigms by which these conflicts are managed are inadequate, because they either deny or unsuccessfully finesse the reality of contradiction between fidelity to patients and society's other expectations of medicine. This reality needs to be more squarely acknowledged. The challenge for ethics and law is not to resolve this tension—an impossible task—but to mediate it in myriad clinical circumstances in a way that preserves the primacy of keeping faith with patients while conceding the legitimacy of society's other expectations of medicine.
ANTIGEN RECOGNITION AND THE IMMUNE RESPONSE
Authors: Maurice E. Bush, Sefik S. Alkan, Danute E. Nitecki, Joel W. Goodman
Journal: The Journal of Experimental Medicine (1972)

L-Tyrosine-p-azobenzenearsonate (RAT) induces cellular immunity without humoral antibody in guinea pigs. Asymmetric bifunctional antigens composed of one RAT moiety and one dinitrophenyl (DNP) group separated by flexible spacers induce anti-RAT cellular immunity and an anti-DNP humoral response. Symmetrical bifunctional antigens of similar design but comprised of two RAT determinants induce cellular immunity without demonstrable anti-RAT antibody. However, when the flexible spacer is replaced by a rigid decaproline chain, humoral anti-RAT responses are provoked. Since RAT contains both electropositive (azo) and electronegative (arsonate) centers, the failure of bifunctional RAT compounds with flexible spacers to induce humoral immunity might be ascribed either to intramolecular stacking, which compromises their bifunctional character, or to interaction of both determinants with receptors on the same cell surface, which would fail to satisfy the requirement for cooperation. In order to distinguish between these alternatives, symmetrical bifunctional antigens composed of two L-tyrosine-p-azophenyltrimethylammonium (TAT) determinants separated by flexible or rigid spacers were synthesized. TAT is immunogenic and does not cross-react with RAT. Furthermore, it contains only electropositive centers and consequently bifunctional molecules do not undergo intramolecular stacking. Immunization with either flexibly or rigidly spaced bifunctional TAT antigens raised anti-TAT antibody. These results conclusively demonstrate that "self-help," cooperation between bone marrow-derived and thymus-derived lymphocytes of identical or similar specificity, can occur, provided the determinants on the antigen are prevented from associating with each other.
Analysis of repetitive DNA distribution patterns in the Tribolium castaneum genome
Authors: Suzhi Wang, Marcé D Lorenzen, Richard W Beeman, Susan J Brown
Journal: Genome biology (2008)

Abstract Background Insect genomes vary widely in size, a large fraction of which is often devoted to repetitive DNA. Re-association kinetics indicate that up to 42% of the genome of the red flour beetle, Tribolium castaneum , is repetitive. Analysis of the abundance and distribution of repetitive DNA in the recently sequenced genome of T. castaneum is important for understanding the structure and function of its genome. Results Using TRF, TEpipe and RepeatScout we found that approximately 30% of the T. castaneum assembled genome is composed of repetitive DNA. Of this, 17% is found in tandem arrays and the remaining 83% is dispersed, including transposable elements, which in themselves constitute 5-6% of the genome. RepeatScout identified 31 highly repetitive DNA elements with repeat units longer than 100 bp, which constitute 7% of the genome; 65% of these highly repetitive elements and 74% of transposable elements accumulate in regions representing 40% of the assembled genome that is anchored to chromosomes. These regions tend to occur near one end of each chromosome, similar to previously described blocks of pericentric heterochromatin. They contain fewer genes with longer introns, and often correspond with regions of low recombination in the genetic map. Conclusion Our study found that transposable elements and other repetitive DNA accumulate in certain regions in the assembled T. castaneum genome. Several lines of evidence suggest these regions are derived from the large blocks of pericentric heterochromatin in T. castaneum chromosomes.
Cardiomyocyte-Specific Loss of Neurofibromin Promotes Cardiac Hypertrophy and Dysfunction
Authors: Junwang Xu, Fraz A. Ismat, Tao Wang, Min Min Lu, Nicole Antonucci, Jonathan A. Epstein
Journal: Circulation Research (2009)

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with a broad array of clinical manifestations, including benign and malignant tumors, and characteristic cutaneous findings. NF1 patients also have an increased incidence of cardiovascular diseases, including obstructive vascular disorders and hypertension. The disease gene, NF1, encodes neurofibromin, a ubiquitously expressed protein that acts, in part, as a Ras-GAP (GTP-ase activating protein), downregulating the activity of activated Ras protooncogenes. In animal models, endothelial and smooth muscle expression of the disease gene is critical for normal heart development and the prevention of vascular disease, respectively.To determine the role of NF1 in the postnatal and adult heart.We generated mice with homozygous loss of the murine homolog Nf1 in myocardium (Nf1mKO) and evaluated their hearts for biochemical, structural, and functional changes. Nf1mKO mice have normal embryonic cardiovascular development but have marked cardiac hypertrophy, progressive cardiomyopathy, and fibrosis in the adult. Hyperactivation of Ras and downstream pathways are seen in the heart with the loss of Nf1, along with activation of a fetal gene program.This report describes a critical role of Nf1 in the regulation of cardiac growth and function. Activation of pathways known to be involved in cardiac hypertrophy and dysfunction are seen with the loss of myocardial neurofibromin.
Health funding expected to grow by 1.9% next year, officials reveal
Authors: A. O'Dowd
Journal: BMJ (2010)

The budget for the NHS is only likely to grow by 1.9% next year, senior officials at the Department of Health have told MPs.

Officials giving evidence to MPs on the parliamentary health select committee said they anticipated a 1.9% rise in funding for 2011-12.

Real growth funding for the NHS has risen an average of 7% every year over the past decade, but next year will mark a significant slowing down in rises as the government will announce its plans for the next spending review period of 2011-12 to 2013-14 on 20 October.

As part of their inquiry into public expenditure, the health committee MPs asked what the government’s …
Medical Nutrition Therapy and Lifestyle Interventions
Authors: Diane M. Reader
Journal: Diabetes Care (2007)

Nutrient intake plays a significant role in the health outcomes of all pregnant women. In a pregnancy complicated by gestational diabetes mellitus (GDM), excellent glucose control is as foundational as appropriate weight gain and adequate nutrient intake. The controversies in GDM management include the following: how far to manipulate energy intake, dietary composition (carbohydrates and fats), and gestational weight gain. Signs that food restrictions have gone too far include weight loss or lack of weight gain, undereating to avoid insulin therapy, positive urinary ketones, and intentional restriction of healthy foods. If a balance between nutrient needs and glucose control cannot be achieved, then concurrent medication therapy is needed to assist in reducing insulin resistance and supplementing insulin production to provide normoglycemia and improved pregnancy outcomes. Medical nutrition therapy is a self-management therapy. Education, support, and follow-up are required to assist the woman to make lifestyle changes essential to successful nutrition therapy. Women with GDM are at increased risk for type 2 diabetes; learning to manage GDM with lifestyle change provides an opportunity to affect personal risk factors and the health of the whole family.
Combination Chemotherapy of Hodgkin's Disease in Private Practice
Authors: Lowell H. Greenberg
Journal: JAMA (1972)

Sixteen patients with advanced Hodgkin's disease were treated with intensive combination chemotherapy (MOPP). Fourteen achieved complete remission. Many had been previously treated with radiation therapy or chemotherapy or both. Toxic effects were minimal and easily controlled. MOPP therapy represents the chemotherapeutic treatment of choice for patients with advanced Hodgkin's disease, and can be safely administered to outpatients, utilizing community medical facilities.
Preeclampsia and Gestational Hypertension Are Associated With Childhood Blood Pressure Independently of Family Adiposity Measures
Authors: J.J. Miranda Geelhoed, Abigail Fraser, Kate Tilling, Li Benfield, George Davey Smith, Naveed Sattar, Scott M. Nelson, Debbie A. Lawlor
Journal: Circulation (2010)

Background— Offspring of women with hypertensive disorders of pregnancy are at increased risk of cardiovascular complications later in life, but the mechanisms underlying these associations are unclear. Our aim was to examine whether adjusting for birth weight and familial adiposity changed the association of hypertensive disorders of pregnancy with offspring blood pressure. Methods and Results— Using data from 6343 nine-year-old participants in the Avon Longitudinal Study of Parents and Children, we examined the association between hypertensive disorders of pregnancy (preeclampsia and gestational hypertension) and offspring blood pressure. Both preeclampsia and gestational hypertension were associated with systolic and diastolic blood pressures in the 9-year-old offspring; after adjustment for parental and own adiposity and for other potential confounders, the mean difference in systolic blood pressure was 2.05 mm Hg (95 confidence interval, 0.72 to 3.38) and 2.04 mm Hg (95 confidence interval, 1.42 to 2.67) for preeclampsia and gestational hypertension, respectively, compared with those with no hypertensive disorders of pregnancy. Equivalent results for diastolic blood pressure were 1.00 mm Hg (95 confidence interval, −0.01 to 2.10) and 1.07 mm Hg (95 confidence interval, 0.60 to 1.54). The association of preeclampsia with offspring systolic and diastolic blood pressures attenuated toward the null with further adjustment for birth weight and gestational age, whereas these adjustments did not attenuate the association of gestational hypertension with offspring blood pressure. Conclusions— The associations of hypertensive disorders of pregnancy with higher offspring blood pressure are not explained by familial adiposity. The mechanisms linking preeclampsia and gestational hypertension with offspring blood pressure may differ, with the former mediated at least in part by the effect of preeclampsia on intrauterine growth restriction.
STUDIES ON THE PHYSIOLOGICAL EFFECTS OF FEVER TEMPERATURES
Authors: Ruth A. Boak, Charles M. Carpenter, Stafford L. Warren
Journal: The Journal of Experimental Medicine (1932)

1. The thermal death time of Trefonema pallidumin extracts from lesions in rabbits' testes was determined in vitro at fever temperatures using the Zinsser-Hopkins and Nichols strains. 2. The criteria to determine the persistence of infectivity of the heated extract were the following: the development of lesions on inoculation into rabbits, dark-field examination of tissue from the lesions, the outcome of blood Wassermann tests, and of reinoculation tests. 3. The thermal death time of the two strains of spirochetes was approximately the same, although the Nichols strain was somewhat the more resistant. In the case of the latter 5 hours at 39°C., 3 hours at 40°C., 2 hours at 41°C., and 1 hour at 41.5°C., were required to render infective extracts innocuous to other rabbits. 4. The thermal death time of T. pallidum in testicular extracts in vitro at fever temperatures is so short as to suggest that induced fever may be useful therapeutically in human syphilis.
Efficacy of fluticasone on cough: a randomised controlled trial
Authors: B. P. Ponsioen, W. C. J. Hop, N. A. Vermue, P. N. R. Dekhuijzen, A. M. Bohnen
Journal: European Respiratory Journal (2005)

Cough may be the consequence of bronchial hyperresponsiveness (BHR) and inflammation. This study was designed to investigate the short-term effects of an inhaled steroid (fluticasone propionate (FP)) on cough, and to determine the effects of smoking, BHR, allergy and forced expiratory volume in one second (FEV1) on the efficacy of FP. In a community-based primary healthcare centre, 135 previously healthy adults suffering from cough for ≥2 weeks were enrolled in a randomised, double-blind, placebo-controlled trial of inhaled FP 500 µg b.i.d. for 2 weeks. Participants completed daily diary cards of lower respiratory tract symptoms. The primary outcome measure was the decrease in mean total daily cough score (0–6) during the second week of treatment. In the FP group, the cough score decreased from 3.8 at baseline to mean± sem 1.4±0.2 during the second week. In the placebo group, this decrease was from 3.8 to 1.9±0.1 and was statistically significantly less. A favourable effect of FP was only detectable in nonsmokers, in whom the score was 0.9 points lower compared with placebo. The clinical relevance of this finding has to be established further. Allergy, FEV1 and BHR at baseline did not affect the efficacy of FP. In conclusion, anti-inflammatory treatment with the inhaled steroid fluticasone propionate reduces cough in otherwise healthy adults who do not smoke.
Vemurafenib Use in an Infant for High-Risk Langerhans Cell Histiocytosis
Authors: Sébastien Héritier, Mathilde Jehanne, Guy Leverger, Jean-François Emile, Jean-Claude Alvarez, Julien Haroche, Jean Donadieu
Journal: JAMA Oncology (2015)

This case report describes the first use of vemurafenib in an infant with BRAF V600E–mutated Langerhans cell histiocytosis, showing improvement in the patient's general health and eventual complete remission.
Less Toxicity by Optimizing Chemotherapy, but Not by Addition of Granulocyte Colony-Stimulating Factor in Children and Adolescents With Acute Myeloid Leukemia: Results of AML-BFM 98
Authors: Ursula Creutzig, Martin Zimmermann, Thomas Lehrnbecher, Norbert Graf, Johann Hermann, Charlotte M. Niemeyer, Alfred Reiter, Jörg Ritter, Michael Dworzak, Jan Stary, Dirk Reinhardt
Journal: Journal of Clinical Oncology (2006)

To improve prognosis in children with acute myeloid leukemia (AML) by randomized comparisons of (1) two short consolidation cycles versus the Berlin-Frankfurt-Muenster (BFM) -type biphasic 6-week consolidation and (2) the prophylactic administration of granulocyte colony-stimulating factor (G-CSF) versus no G-CSF. Further, therapy for standard risk patients was intensified by addition of a second induction, HAM (high-dose cytarabine and mitoxantrone).Four hundred seventy-three patients younger than 18 years with de novo AML were enrolled in trial AML-BFM 98. Patients received five courses of intensive chemotherapy, cranial irradiation, and 1-year maintenance therapy.Four hundred eighteen patients (88%) achieved remission. Compared with trial AML-BFM 93, early deaths decreased from 7.4 to 3.2% (P = .005), and 5-year overall survival increased from 58% to 62% (log-rank P = .03). Both types of consolidation therapy led to similar outcome (event-free survival, 51% v 50%), but in the two-cycle arm, treatment duration was shorter (median duration, 15 days), and treatment related mortality was lower (five v nine patients). G-CSF shortened neutropenia, but did not reduce the rate of severe infections. Intensification of induction therapy did not improve prognosis of standard-risk patients (event-free survival, 62% v 67%).Overall results were improved by neither the administration of G-CSF nor by cycle therapy; however, the latter was easier to perform. Compared with study AML-BFM 93, therapy intensification with HAM in standard-risk patients did not result in improved prognosis. Future treatment designs have to balance intensification of treatment with higher toxicity, improve supportive care, and to consider alternative treatment strategies.
Halothane anaesthesia and liver damage.
Authors: J Neuberger, R Williams
Journal: BMJ (1984)

A recent experience of the senior author when addressing a meeting of anaesthetists prompted this review, since it was apparent that there was still considerable disagreement between hepatologists and anaesthetists over the association between liver cell damage and halothane anaesthesia and the measures by which the risk could be minimised.Although during the 1960s and 1970s the evidence was hotly debated, there has since been increasing acceptance, both clinical and experimental, of a strong prima facie case for an association.'" Two, probably distinct, forms of liver damage have been defined.'2Serum aminotransferase activities are raised in up to a fifth of patients anaesthetised with halothane during the first and second postoperative weeks (type I).Such minor forms of liver injury are to be distinguished from the rare occurrence of massive liver cell necrosis (type II).Three well controlled studies of minor reactions have been reported from Britain.s 6 8 Significant rises in serum aspartate
Antioxidants Block Prostate Cancer in <b> <i>Lady</i> </b> Transgenic Mice
Authors: Vasundara Venkateswaran, Neil E. Fleshner, Linda M. Sugar, Laurence H. Klotz
Journal: Cancer Research (2004)

Abstract The development of chemopreventive agents against prostate cancer would benefit from conclusive evidence of their efficacy in animal models that emulate human disease. To date there has been little in vivo evidence supporting their preventive capabilities. The 12T-10 Lady transgenic model spontaneously develops localized prostatic adenocarcinoma and neuroendocrine cancer followed by metastases, recapitulating the natural history of human prostate cancer in many respects. Using male Lady version of the transgenic adenocarcinoma of the mouse prostate mice, we show that administration of antioxidants (vitamin E, selenium, and lycopene) in the diet dramatically inhibits prostate cancer development and increases the disease free survival. Treatment of animals with the antioxidants resulted in a 4-fold reduction in the incidence of prostate cancer compared with the untreated animals. Prostate cancer developed in 73.68% (14 of 19) and 100% (19 of 19) of the animals from the standard and high fat diet, respectively. In contrast, only 10.53% (2 of 19) and 15.79% (3 of 19; P &amp;lt; 0.0001) of the animals in the standard and high fat diets supplemented with antioxidants developed tumors. The micronutrients were well tolerated with no evidence of antioxidant-related toxicity. Histopathological analysis confirmed absence of cancer in the additive treated groups. Immunohistochemistry demonstrated a strong correlation between disease-free state and increased levels of the prognostic marker p27Kip1 and a marked decrease in proliferating cell nuclear antigen expression. These observations provide support for the chemopreventive effect of these micronutrients and some clues as to their mechanism of action.
Depressive Symptoms in Schizophrenia
Authors: Sidney Zisook, Lou Ann McAdams, Julie Kuck, M. Jackuelyn Harris, Anne Bailey, Thomas L. Patterson, Lewis L. Judd, Dilip V. Jeste
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The authors assessed the presence and severity of depressive symptoms, as well as their associations with other clinical measures, in a group of mid- to late-life patients with schizophrenia who were not in a major depressive episode or diagnosed with schizoaffective disorder. METHOD: Sixty outpatients with schizophrenia between the ages of 45 and 79 years and 60 normal comparison subjects without major neuropsychiatric disorders, proportionally matched for age and gender, were studied. Depressive symptoms were rated primarily with the Hamilton Depression Rating Scale. Standardized instruments were also used to measure global psychopathology, positive and negative symptoms, abnormalities of movement, and global cognitive status. RESULTS: Depressive symptoms were more frequent and more severe in schizophrenic patients than in normal comparison subjects; 20% of the women with schizophrenia had a Hamilton depression scale score of 17 or more. Severity of depressive symptoms correlated with that of positive symptoms but not with age, gender, negative symptoms, extrapyramidal symptoms, or neuroleptic dose. CONCLUSIONS: Depressive symptoms are common in older patients with schizophrenia. They may be an independent, core component of the disorder or, alternatively, may be a by-product of severe psychotic symptoms.
Myocardial angiogenesis after plasmid or adenoviral VEGF-A165 gene transfer in rat myocardial infarction model
Authors: X HAO, A MANSSONBROBERG, K GRINNEMO, A SIDDIQUI, G DELLGREN, L BRODIN, C SYLVEN
Journal: Cardiovascular Research (2006)

To compare gene transfer of plasmid (P) and adenovirus (Ad) encoding human vascular endothelial growth factor-A165 (hVEGF-A165) angiogenic efficacy and adverse effects as regards apoptosis and ectopic expression of the transgene in a rat myocardial infarction model.Myocardial infarction was provoked in Fisher rats. One week later, PhVEGF-A165, PLacZ, AdhVEGF-A165, or AdLacZ was transferred intramyocardially along the border of the myocardial infarction. hVEGF-A expression was detected with ELISA. Myocardial vessel density was analyzed 1 and 4 weeks after gene transfer. Apoptosis was detected by TUNEL staining. Cardiac function was assessed with Tissue Doppler Velocity Imaging.Although AdhVEGF-A165 had substantially higher myocardial hVEGF-A expression than PhVEGF-A165, AdhVEGF-A165 and PhVEGF-A165 induced angiogenic effects to a similar extent with maintained increased arteriolar density after 4 weeks of gene transfer (p < 0.05). The two treatments also improved left ventricular function similarly. Adenoviral gene transfer induced a higher number of TUNEL positive cells than plasmid (p < 0.02). Ectopic expression of the transgene was present with both vectors but substantially higher after adenoviral gene transfer.AdhVEGF-A165 has no obvious angiogenic advantage over PhVEGF-A165 but more side effects at least in a rat myocardial infarction model. This indicates that PhVEGF-A165 might be more applicable for therapeutic angiogenesis than AdhVEGF-A165.
Detection of peripheral arterial disease in patients presenting for coronary angiography and/or intervention patients study (PIPS)
Authors: Issam Moussa, Roxana Mehran, Gary S. Roubin, Sriram Iyer, Thosaphol Limpijankit, Monica Losquadro, Lynne Glasser, Heather Klein, Steven Slack, Martin B. Leon, Jeffrey W. Moses
Journal: Journal of the American College of Cardiology (2003)
Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial
Authors: Richard B Moss, Patrick A Flume, J Stuart Elborn, Jon Cooke, Steven M Rowe, Susanna A McColley, Ronald C Rubenstein, Mark Higgins
Journal: The Lancet Respiratory Medicine (2015)