tbuckley/cabot-search huggingface dataset:
Differential cardiac responses induced by nicotine sensitive canine atrial and ventricular neurones
Authors: B.-X. Yuan, J L Ardell, D A Hopkins, J A Armour
Journal: Cardiovascular Research (1993)

The aim was to study the locations and functions of atrial and ventricular nicotine sensitive neurones.In anaesthetised open chest dogs, cardiovascular effects elicited by nicotine (100 micrograms in 0.1 ml 0.9% saline), administered at specific loci of in situ atrial and ventricular ganglionated plexi, were studied before and after decentralisation.Cardiovascular responses were elicited when 41% of atrial and 36% of ventricular ganglionated plexus loci were studied. Subsequently, ganglia were identified adjacent to active sites. When cardiovascular responses were elicited, either tachycardia or bradycardia was induced, depending on the locus investigated. When tachycardia occurred, atrial and/or ventricular forces were augmented. When bradycardia occurred, atrial forces were suppressed. Ventricular fibrillation was induced in two animals when ventricular ganglionated plexus loci were investigated. Cardiovascular responses were not elicited when up to 2000 micrograms of nicotine were administered adjacent to intrinsic cardiac axons, indicating that responses were not primarily due to axonal effects. Control injections of saline (0.1 ml) into active loci did not elicit cardiovascular responses. Following acute decentralisation, responses initiated by nicotine were attenuated or eliminated. Depressor responses were no longer elicited following atropine administration, nor augmentor ones following propranolol administration.(1) The canine heart contains nicotine sensitive neurones which can induce either augmentor or depressor cardiac effects. (2) Nicotine sensitive atrial neurones modify primarily, but not exclusively, atrial tissues, whereas ventricular ones modify primarily, but not exclusively, ventricular tissues. (3) Nicotine sensitive intrinsic cardiac neurones can interact with central neurones to modulate the heart.
S3-7: Everolimus for Postmenopausal Women with Advanced Breast Cancer: Updated Results of the BOLERO-2 Phase III Trial.
Authors: GN Hortobagyi, M Piccart, H Rugo, H Burris, M Campone, S Noguchi, M Gnant, KI Pritchard, L Vittori, P Mukhopadhyay, T Sahmoud, D Lebwohl, J Baselga
Journal: Cancer Research (2011)

Abstract Background: The mTOR pathway is constitutively activated in hormone-resistant advanced breast cancer (ABC). In phase II trials, everolimus (EVE) showed promising efficacy both as monotherapy and in combination with endocrine therapy in patients with estrogen receptor-positive (ER+) ABC. This double-blind, placebo-controlled, phase III study evaluated EVE plus exemestane (EXE) in patients with ER+ ABC refractory to letrozole or anastrozole. Patients and Methods: Eligible patients were randomized (2:1) to EXE (25 mg/day) with EVE (10 mg/day) or with matching placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, response rate, quality of life (QoL), and safety. Results: 724 patients were randomized (485: EVE+EXE; 239: EXE). Baseline characteristics were well balanced; median age was 62 years, 56% had visceral involvement, and 84% had documented benefit from previous endocrine therapy, which included letrozole or anastrozole (100%), tamoxifen (48%), fulvestrant (16%), and chemotherapy for advanced disease (25%). This analysis is based on 457 events and median follow-up of 12.5 months. PFS by investigator assessment showed a hazard ratio (HR) of 0.44 (95% CI: 0.36−0.53) and a median duration of 7.4 (EVE+EXE) vs 3.2 months (EXE) (P&amp;lt;1 × 10−16) and 12-month estimate of 31% vs 10%. PFS by central assessment showed an HR of 0.36 (95% CI: 0.28−0.45) and a median duration of 11.0 (EVE+EXE) vs 4.1 months (EXE) (P&amp;lt;1 × 10−16) and 12-month estimate of 48% vs 18%. Response rates and clinical benefit rate were also higher for EVE+EXE (12.0% vs 1.3% and 50.5% vs 25.5%). A total of 138 patients died; 17.3% in the EVE+EXE arm and 22.6% in the EXE arm. The most common grade 3/4 adverse events were stomatitis (8% vs 1%), anemia (7% vs 1%), hyperglycemia (5% vs &amp;lt; 1%), dyspnea (4% vs 1%), and fatigue (4% vs 1%) for the EVE+EXE and EXE groups, respectively. Grade 3 pneumonitis was observed in patients receiving EVE (3% vs 0%). No difference in time to deterioration of QoL was observed. EVE increased EXE steady-state Cmin and Cmax levels by 45% and 64%, respectively, with no difference in estradiol levels. Serum markers of bone resorption and bone formation increased in the EXE arm and generally decreased in the EVE+EXE arm. Conclusion: The addition of EVE to EXE is associated with significant and sustained prolongation of PFS. Adverse events were higher in the combination arm but manageable by dose interruption and/or reduction and did not affect QoL. EVE in combination with an aromatase inhibitor is a promising therapeutic option for women with hormone receptor-positive advanced breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S3-7.
The Harveian Lectures on Prognosis and Treatment in Pulmonary Tuberculosis: Delivered before the Harveian Society of London, November, 1900
Authors: R. Maguire
Journal: BMJ (1900)

IN choosing a subject for these lectures one cannot but be influenced by the name and work of Harvey.He employed a combination of the methods of Bacon and Newton, and essentially insisted upon observance of facts, making his
Rationale for a New Generation of Indicators for Coastal Waters
Authors: Gerald Niemi, Denice Wardrop, Robert Brooks, Susan Anderson, Valerie Brady, Hans Paerl, Chet Rakocinski, Marius Brouwer, Barbara Levinson, Michael McDonald
Journal: Environmental Health Perspectives (2004)

More than half the world's human population lives within 100 km of the coast, and that number is expected to increase by 25% over the next two decades. Consequently, coastal ecosystems are at serious risk. Larger coastal populations and increasing development have led to increased loading of toxic substances, nutrients and pathogens with subsequent algal blooms, hypoxia, beach closures, and damage to coastal fisheries. Recent climate change has led to the rise in sea level with loss of coastal wetlands and saltwater intrusion into coastal aquifers. Coastal resources have traditionally been monitored on a stressor-by-stressor basis such as for nutrient loading or dissolved oxygen. To fully measure the complexities of coastal systems, we must develop a new set of ecologic indicators that span the realm of biological organization from genetic markers to entire ecosystems and are broadly applicable across geographic regions while integrating stressor types. We briefly review recent developments in ecologic indicators and emphasize the need for improvements in understanding of stress-response relationships, contributions of multiple stressors, assessments over different spatial and temporal scales, and reference conditions. We provide two examples of ecologic indicators that can improve our understanding of these inherent problems: a) the use of photopigments as indicators of the interactive effects of nutrients and hydrology, and b) biological community approaches that use multiple taxa to detect effects on ecosystem structure and function. These indicators are essential to measure the condition of coastal resources, to diagnose stressors, to communicate change to the public, and ultimately to protect human health and the quality of the coastal environment.
Case of Scirrhus of the Gall-Bladder; with Observations
Authors: R. Burridge
Journal: BMJ (1845)

to the Taunton and Somerset Hotspital.Mary Rice, aged 42, a patient of the Taunton and Somerset Hospital, under my care.About four months, previousJy to admission, the catamenia ceaed to appear, and about ten weeks afterwards she was affected with jaundice, for which she applied to the parochial nmedical officer.Purgatives and mercury having been found inefficient, she was finally advised to enter the Hospital.Upon admission the whole surface of the body and the conjunctiva presented the greenish yellow hue, as described by Dr. flaillie in green jaundice.There
Paternal Transmission of Maleness in XX Human Beings
Authors: Richard Kasdan, Howard R. Nankin, Philip Troen, Niel Wald, Sylvia Pan, Takumi Yanaihara
Journal: New England Journal of Medicine (1973)

Phenotypic maleness was observed in a 7 1/2-year-old child and his father with an XY karyotype. Two brothers and a paternal uncle were found to have an XX sex-chromosome constitution. The boys' mother and sister were XX karyotype. Four of these five males had an extra small marker chromosome that did not appear to be involved in sex determination. Barr body counts of buccal smears and skin cells, drumstick counts, repeated lymphocyte and skin karyotypes, and quinacrine fluorescence studies of metaphase spreads, peripheral blood smears, and buccal smears were all consistent with the observed sex-chromosome findings. Except for the father's brother, who had partial testicular failure, the evaluated family members had appropriately normal serum concentrations of luteinizing and follicle-stimulating hormones, and total androgen. In addition, there appeared to be a preponderance of males in the father's sibship and among their offspring. Two separate male-determining loci seemed to be inherited in this family: the Y chromosome and a functioning autosomal locus.
Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity?
Authors: Ulrike Bacher, Evgeny Klyuchnikov, Jennifer Le-Rademacher, Jeanette Carreras, Philippe Armand, Michael R. Bishop, Christopher N. Bredeson, Mitchell S. Cairo, Timothy S. Fenske, Cesar O. Freytes, Robert Peter Gale, John Gibson, Luis M. Isola, David J. Inwards, Ginna G. Laport, Hillard M. Lazarus, Richard T. Maziarz, Peter H. Wiernik, Harry C. Schouten, Shimon Slavin, Sonali M. Smith, Julie M. Vose, Edmund K. Waller, Parameswaran N. Hari
Journal: Blood (2012)
Cardiac Troponin I: A Reliable Marker and Early Myocardial Involvement with Meningoencephalitis after Fatal Enterovirus-71 Infection
Authors: Y.-F. Huang, P.-C. Chiu, C.-C. Chen, Y.-Y. Chen, K.-S. Hsieh, Y.-C. Liu, P.-H. Lai, H.-W. Chang
Journal: Journal of Infection (2003)
Oral Cephalexin and Ampicillin: Antimicrobial Activity, Recovery in Urine, and Persistence in Blood of Uremic Patients
Authors: CALVIN M. KUNIN
Journal: Annals of Internal Medicine (1970)

A new orally absorbed cephalosporin derivative (cephalexin) and potassium ampicillin were studied in subjects with normal and decreased renal function. A 1-week course of each drug gave adequate therapeutic blood and urinary concentrations, without evidence of cumulation or toxicity in normal subjects. Almost all of the cephalexin and about one half of the ampicillin were recovered in the urine. The same treatment in uremic patients was associated with elevated concentrations of both drugs in the serum with only modest accumulation over 1 week. Concentrations in urine progressively rose and were adequate for most urinary tract organisms against which these agents are active. One of five patients had a fall in creatinine clearance 2 weeks after the last dose of cephalexin, but renal function later improved, and the effect cannot be proved drug-related. Both cephalexin and ampicillin may be useful in treatment of urinary infections in moderately uremic patients whose creatinine clearance exceeds 9 to 10 ml/min.
New funding mechanism is launched to combat malaria
Authors: P. Moszynski
Journal: BMJ (2009)

Fighting malaria is part of the United Nations’ sixth millennium development goal, yet a new generation of frontline drugs remains out of reach of most patients, so a new £150m (€170m; $220m) scheme has been developed to subsidise their cost.

Launched last week in Oslo, the Affordable Medicines Facility for Malaria is an innovative financing mechanism designed to expand access to artemisinin based combination drugs, the most effective treatment.

In 2006 about 250 million people developed malaria, of whom nearly a million died. Malaria parasites are becoming increasingly resistant to older drugs, such as chloroquine and pyrimethamine with sulfadoxine, which are still often used because they are relatively cheap.

“The age when the …
TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity
Authors: Ganesan Ramesh, W. Brian Reeves
Journal: Journal of Clinical Investigation (2002)

The purpose of these studies was to examine the role of cytokines in the pathogenesis of cisplatin nephrotoxicity. Injection of mice with cisplatin (20 mg/kg) led to severe renal failure. The expression of cytokines, chemokines, and ICAM-1 in kidney was measured by ribonuclease protection assays and RT-PCR. We found significant upregulation of TNF-α, TGF-β, RANTES, MIP-2, MCP-1, TCA3, IL-1β, and ICAM-1 in kidneys from cisplatin-treated animals. In addition, serum, kidney, and urine levels of TNF-α measured by ELISA were increased by cisplatin. Inhibitors of TNF-α production (GM6001, pentoxifylline) and TNF-α Ab’s reduced serum and kidney TNF-α protein levels and also blunted the cisplatin-induced increases in TNF-α, TGF-β, RANTES, MIP-2, MCP-1, and IL-1β, but not ICAM-1, mRNA. In addition, the TNF-α inhibitors also ameliorated cisplatin-induced renal dysfunction and reduced cisplatin-induced structural damage. Likewise, TNF-α–deficient mice were resistant to cisplatin nephrotoxicity. These results indicate cisplatin nephrotoxicity is characterized by activation of proinflammatory cytokines and chemokines. TNF-α appears to play a central role in the activation of this cytokine response and also in the pathogenesis of cisplatin renal injury.
It's not so much what you know
Authors: D. Cohen
Journal: BMJ (2009)

Hold the front page—a report last month by the former health secretary Alan Milburn declared that Britain’s top professions, such as law and medicine, are closed to all but the most well-off families. Figures this week from the Universities and Colleges Admissions Service (UCAS) showing that today’s medical students are far more likely than five years ago to have been privately educated lend support to this claim.

And stop the presses—the BMA’s Medical Students Committee is using this opportunity to campaign on tuition fees. Now, I’m no fan of tuition fees, particularly when you consider that the current economic climate was caused in part by unsustainable debt. In …
Niche construction in biological and philosophical theories
Authors: Peter Godfrey-Smith
Journal: Behavioral and Brain Sciences (2000)

I distinguish different versions of the “niche construction” idea. Some are primarily scientific, while others are more philosophical. Laland, Odling-Smee &amp; Feldman's is mostly scientific, but given that fact, there are some changes they could make to their account. I also compare the target article to Lewontin's classic 1983 paper.
Survival after valve replacement for aortic regurgitation: Prediction from noninvasive contractility measurement and comparison with census-expected survival
Authors: Jeffrey S. Borer, Edmund M. Herrold, Phyllis G. Supino, Clare A. Hochreiter, Richard B. Devereux, Mary J. Roman, Paul D. Kligfield, O.Wayne Isom, Karl H. Krieger, Andrew Yin, Leonard Hearne, N.Philip Ross
Journal: Journal of the American College of Cardiology (2003)
Dressings in hand sepsis.
Authors: J. Sneddon
Journal: BMJ (1969)

Present StudyForty-six patients suffering from a septic condition of the hand treated between 14 November and 11 December 1966 were required to attend daily for a week unless healing had occurred earlier.Dry gauze dressings were applied by the nursing staff after the doctor had seen the patient.Between 2 January and 29 January 1967, 60 patients suffer- ing from septic hands were treated under the new regimen on 1 August
Adopted Children and Their Families in the Evaluation of Nature-Nurture Interactions in the Schizophrenic Disorders
Authors: Paul H. Wender
Journal: Annual Review of Medicine (1972)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Intracellular Calcium and Myocardial Contractility
Authors: JOSEF SUKO, JOHN H.K. VOGEL, CHARLES A. CHIDSEY
Journal: Circulation Research (1970)

The function of the sarcoplasmic reticulum of the failing myocardiums was studied in vitro by comparing calcium uptake and calcium-activated ATPase in microsomes prepared from hearts of control calves and calves in which right ventricular failure developed during experimentally induced pulmonary hypertension. The rate of calcium uptake averaged .147 µmole·mg -1 ·min -1 at 25°C in the presence of oxalate in control preparations and was significantly reduced in preparations from failing right ventricles (avg .086 µmoles·mg -1 ·min -1 ). Calcium-activated ATPase was also diminished significantly in failure (avg .184 compared to .073 µmoles·mg -1 ·min -1 ). Although two preparations also showed diminished calcium activities in the nonfailing left ventricle, group these activities were not significantly depressed in preparations from ventricle in calves with failure. A similar reduction in calcium activities observed at 37°C with preparations further purified by sucrose gradient centrifugation. The uptake capacity of microsomes, measured as calcium uptake in the absence of oxalate, was not diminished in the preparations from failing hearts. Mitochondrial contamination did not appear to be a factor since azide inhibited calcium activity almost completely in mitochondria, whereas inhibition was less than 10% in microsomes of both control and failing hearts. Ouabain had no effect on the microsomes from failing hearts. These studies indicate that there is a defect in calcium transport in microsomes and a functional abnormality of the sarcoplasmic reticulum in the intact myocardial cell in heart failure which could lead to changes in the excitation-contraction coupling mechanisms of clinical importance.
The role of eosinophils in the pathogenesis of atopic dermatitis ‐ eosinophil granule proteins as markers of disease activity
Authors: A. Kapp
Journal: Allergy (1993)

Currently, there is a large body of evidence that atopic dermatitis (AD) has an Immunologic basis. Atopy‐specific helper T cells (Th2‐like T cells) may play a pathogenetic role by producing and releasing cytokines rele van t for the allergic inflammation, such as IL‐4, IL‐5, and other growth factors. Eosinophils are believed to be of major importance as effector cells mediating the pathogenetically rele van t late‐phase reaction which is associated with a significant destruction of the surrounding tissue. Accordingly, a significant preactivation of peripheral blood eosinophils was detected in AD patients, leading to an enhanced susceptibility of these cells to distinct stimuli such as IL‐5. Toxic proteins, such as eosinophil cationic protein (ECP), contained in the matrix and the core of secondary granules of eosinophils, may play an important role by propagating the allergic inflammatory process and by modulating the immune response. The pathogenetic role of eosinophils in AD is further supported by the detection of these proteins in the eczematous skin of patients. Furthermore, recent data point to a significant correlation between disease activity and deposition of eosinophil granule content: ECP serum levels were significantly increased in AD patients. In addition, ECP levels correlated with the disease activity. Moreover, clinical improvement was associated with a decrease of both the clinical score and serum ECP levels. These data clearly indicate that activated eosinophils may play a major role in the allergic inflammatory process of AD. Therefore, modulation of eosinophil activation could prove to be an important pharmacologic modality for the treatment of AD.
The tetraspanin CD9 regulates migration, adhesion, and homing of human cord blood CD34+ hematopoietic stem and progenitor cells
Authors: Kam Tong Leung, Kathy Yuen Yee Chan, Pak Cheung Ng, Tze Kin Lau, Wui Man Chiu, Kam Sze Tsang, Chi Kong Li, Carrie Ka Lai Kong, Karen Li
Journal: Blood (2010)
Education for Registered Nurses
Authors: Georgeen H. DeChow
Journal: JAMA (1968)

The first schools of nursing in the United States were established in the early 1870's in Massachusetts, Connecticut, and New York. They emerged in response to a heightened sense of social responsibility for community health and welfare. The Crimean War and the work of Florence Nightingale, followed by the US Civil War, had focused the attention of this nation on the need for nurses and the necessity of devising a system for their education. Adopting the Nightingale pattern, early schools were created independently of hospitals, but lacking financial endowment were soon absorbed by the institutions with which they were associated. The effect was to inextricably bind nursing education to the hospital setting.  In the intervening 100 years, several hundred hospital or diploma schools of nursing have developed. To keep pace with changing educational patterns and needs, the baccalaureate nursing program in the university setting and, more recently, the junior college
NASAL REFLEXES.Read before the American Rhinological Association, Louisville, October, 1890.
Authors: A. B. THRASHER
Journal: JAMA (1890)

There is perhaps no department of modern rhinology more interesting to the specialist or more prolific in material than "nasal reflexes." Indeed, so fertile has been the field that much opprobrium has fallen to our lot by the great diversity of diseases and multiplicity of symptoms which we have attributed to this cause. It does not seem at all strange to the surgeon that<i>morbus coxarius</i>should attract our attention by pain in the knee-joint; but he is skeptical when we refer a post-auricular neuralgia to a hypertrophic turbinate. For a thorough understanding of these neuroses we are perhaps more indebted to Hack, of Freiburg, than to any other one man. His monograph on the subject referred to cases of asthma, nightmare, cough, migraine, sneezing neuralgias, swelling and redness of the skin of the nose, etc., which he had for the most part successfully treated by cauterizing the erectile bodies