tbuckley/cabot-search huggingface dataset:
Symptoms, adverse effects, and complications associated with dobutamine stress echocardiography. Experience in 1118 patients.
Authors: H Mertes, S G Sawada, T Ryan, D S Segar, R Kovacs, J Foltz, H Feigenbaum
Journal: Circulation (1993)

BACKGROUND The use of dobutamine stress echocardiography for the evaluation of coronary artery disease is rapidly expanding. New applications of the technique are being investigated in a wide variety of patients including those with advanced coronary artery disease. Despite its widespread use, the safety of dobutamine stress echocardiography has not been sufficiently documented. METHODS AND RESULTS A consecutive series of 1118 patients undergoing dobutamine stress echocardiography for evaluation of known or suspected coronary artery disease form the basis of this report. Dobutamine stress testing was performed for evaluation of chest pain, risk assessment before noncardiac surgery, after recent myocardial infarction, or as a part of ongoing research protocols. Over the study period, the maximal dose of dobutamine used was increased from 30 to 50 micrograms/kg per minute, and atropine was used in 420 (37%) patients. There were no occurrences of death, myocardial infarction, or episodes of sustained ventricular tachycardia as a result of dobutamine stress testing. The major reasons for test termination were achievement of target heart rate in 583 patients (52.1%), maximum dose in 255 (22.8%), and angina pectoris in 142 (13%). The test was terminated in 36 (3%) patients because of noncardiac side effects including nausea, anxiety, headache, tremor, and urgency. Angina pectoris occurred in 216 (19.3%) patients. Sublingual nitroglycerin, a short-acting beta-blocker, or both types of medication were administered in 80 of these patients for relief of angina pectoris. None required intravenous nitroglycerin. A total of 736 (65%) patients had stable sinus rhythm throughout the test. The most common arrhythmias were frequent premature ventricular complexes (six or more per minute) in 172 patients (15%), and frequent premature atrial complexes in 86 (8%). There were 40 patients with nonsustained ventricular tachycardia. None had symptoms associated with the tachycardia, and only one received specific pharmacological treatment to prevent recurrence of the arrhythmia after the test was terminated. The patients who were evaluated after recent myocardial infarction and those who received atropine did not have a higher frequency of ventricular tachycardia compared with those without recent infarction and those not receiving atropine. CONCLUSIONS Dobutamine stress echocardiography was safely performed using supplemental atropine and an aggressive dosing protocol. Noncardiac side effects were usually minor. Arrhythmias were well tolerated and rarely required treatment. In this study, serious complications from myocardial ischemia did not occur. Symptomatic ischemia was effectively treated with test termination, sublingual nitroglycerin, or short-acting beta-blockers.
Gap Junction Remodeling and Spironolactone-Dependent Reverse Remodeling in the Hypertrophied Heart
Authors: Jiaxiang Qu, Frank M. Volpicelli, Luis I. Garcia, Nefthi Sandeep, Jie Zhang, Lucrecia Márquez-Rosado, Paul D. Lampe, Glenn I. Fishman
Journal: Circulation Research (2008)

Pressure overload is a common pathological insult to the heart and the resulting hypertrophy is an independent risk factor for sudden cardiac death. Gap junction remodeling (GJR) has been described in hypertrophied hearts; however, a detailed understanding of the remodeling process and its effects on impulse propagation is lacking. Moreover, there has been little progress developing therapeutic strategies to diminish GJR. Accordingly, transverse aortic banding (TAC) was performed in mice to determine the effects of progressive pathological hypertrophy on connexin (Cx)43 expression, posttranslational phosphorylation, gap junction assembly, and impulse propagation. Within 2 weeks after TAC, total and phospho-Cx43 abundance was reduced and incorporation of Cx43 into gap junctional plaques was markedly diminished. These molecular changes were associated with progressive slowing of impulse propagation, as determined by optical mapping with voltage-sensitive dyes. Treatment with the aldosterone receptor antagonist spironolactone, which has been shown to diminish sudden arrhythmic death in clinical trials, was examined for its effects on GJR. We found that spironolactone blunted the development of GJR and also potently reversed established GJR, both at the molecular and functional levels, without diminishing the extent of hypertrophy. These data suggest a potential mechanism for some of the salutary electrophysiological and clinical effects of mineralocorticoid antagonists in myopathic hearts.
Progesterone, prolactin, and gynaecomastia in men with liver disease.
Authors: M J Farthing, J R Green, C R Edwards, A M Dawson
Journal: Gut (1982)

Plasma progesterone was raised in 36 of 50 (72%) men with liver disease compared with 20 healthy male control subjects. Plasma progesterone was significantly higher in men with non-alcoholic cirrhosis with gynaecomastia than those without, but no similar relationship was found in men with alcoholic fatty change and alcoholic cirrhosis. Hyperprolactinaemia was found in 14% of men with liver disease but levels were unrelated to the presence of gynaecomastia. Increased circulating levels of progesterone and prolactin alone do not explain the development of gynaecomastia in patients with liver disease, but progesterone may be an additional factor acting in association with the known disturbances of other sex steroids.
Characterization of iron-mediated peroxidative injury in isolated hepatic lysosomes.
Authors: I T Mak, W B Weglicki
Journal: Journal of Clinical Investigation (1985)

Peroxidative degradation of the lysosomal membrane and the resultant release of hydrolytic enzymes may be responsible for hepatocellular injury in iron toxicity. In this study, highly purified hepatic lysosomes were exposed to iron salts in vitro; the nature of this iron-mediated process of injury and the susceptibility of the lysosomal integrity were studied. Native hepatic lysosomes from rats were isolated by free flow electrophoresis. Incubation of the lysosomes at 37 degrees C with Fe3+-ADP in the presence of ascorbate resulted in rapid generation of malondialdehyde, which approached a plateau at 20 min. Subsequently, the loss of lysosomal latency, determined as an increased percentage free activity of N-acetyl-beta-glucosaminidase, also occurred and reached a maximum loss at 30 min. The half-maximal level of ascorbate, required to promote the Fe3+-ADP mediated lysosomal peroxidation, was approximately 10 microM; high concentrations of ascorbate were inhibitory and half-maximal inhibition was achieved at a concentration of 2 mM. The iron-mediated lysosomal peroxidation was not inhibited by most active oxygen scavengers and appeared to depend solely on the generation of Fe2+ species. When a fresh solution of Fe2+ was incubated with the lysosomes, both the extent of lipid peroxidation and the degree of latency loss increased as a function of increasing Fe2+ concentration. High concentrations of Fe2+ stimulated lysosomal lipid peroxidation instantaneously and reached the highest level within 10 min; whereas the subsequent maximum loss of latency was achieved within 20 min. Both the MDA formation and the loss of latency in either the Fe3+-ADP + ascorbate or the Fe2+ system were effectively prevented by the presence of vitamin A or vitamin E.
Dual Angiogenic and Neurotrophic Effects of Bone Marrow–Derived Endothelial Progenitor Cells on Diabetic Neuropathy
Authors: Jin-Ok Jeong, Mee-Ohk Kim, Hyongbum Kim, Min-Young Lee, Sung-Whan Kim, Masaaki Ii, Jung-uek Lee, Jiyoon Lee, Yong Jin Choi, Hyun-Jai Cho, Namho Lee, Marcy Silver, Andrea Wecker, Dong-Wook Kim, Young-sup Yoon
Journal: Circulation (2009)

Background— Endothelial progenitor cells (EPCs) are known to promote neovascularization in ischemic diseases. Recent evidence suggested that diabetic neuropathy is causally related to impaired angiogenesis and deficient growth factors. Accordingly, we investigated whether diabetic neuropathy could be reversed by local transplantation of EPCs. Methods and Results— We found that motor and sensory nerve conduction velocities, blood flow, and capillary density were reduced in sciatic nerves of streptozotocin-induced diabetic mice but recovered to normal levels after hind-limb injection of bone marrow–derived EPCs. Injected EPCs were preferentially and durably engrafted in the sciatic nerves. A portion of engrafted EPCs were uniquely localized in close proximity to vasa nervorum, and a smaller portion of these EPCs were colocalized with endothelial cells. Multiple angiogenic and neurotrophic factors were significantly increased in the EPC-injected nerves. These dual angiogenic and neurotrophic effects of EPCs were confirmed by higher proliferation of Schwann cells and endothelial cells cultured in EPC-conditioned media. Conclusions— We demonstrate for the first time that bone marrow-derived EPCs could reverse various manifestations of diabetic neuropathy. These therapeutic effects were mediated by direct augmentation of neovascularization in peripheral nerves through long-term and preferential engraftment of EPCs in nerves and particularly vasa nervorum and their paracrine effects. These findings suggest that EPC transplantation could represent an innovative therapeutic option for treating diabetic neuropathy.
My Cuban experience
Authors: A A Palejwala
Journal: BMJ (2000)

Contributors: MFH, as principal investigator, had primary responsibility for the study design, administration, quality assurance, planning of statistical analyses, and writing of the manuscript.JMZ, as project coordinator, was responsible for overseeing data collection, intervention delivery, and data preparation and also conducted statistical analyses and contributed to writing the manuscript.GEM collaborated on design of measures, statistical analyses, and editing the manuscript.CRH conducted statistical analyses and assisted with study design and editing the manuscript.JTB conducted urine cotinine analyses and assisted with interpretation of results and editing the manu-
Neuronal eotaxin and the effects of ccr3 antagonist on airway hyperreactivity and M2 receptor dysfunction
Authors: A. D. Fryer
Journal: Journal of Clinical Investigation (2005)

Eosinophils cluster around airway nerves in patients with fatal asthma and in antigen-challenged animals. Activated eosinophils release major basic protein, which blocks inhibitory M2 muscarinic receptors (M2Rs) on nerves, increasing acetylcholine release and potentiating vagally mediated bronchoconstriction. We tested whether GW701897B, an antagonist of CCR3 (the receptor for eotaxin as well as a group of eosinophil active chemokines), affected vagal reactivity and M2R function in ovalbumin-challenged guinea pigs. Sensitized animals were treated with the CCR3 antagonist before inhaling ovalbumin. Antigen-challenged animals were hyperresponsive to vagal stimulation, but those that received the CCR3 antagonist were not. M2R function was lost in antigen-challenged animals, but not in those that received the CCR3 antagonist. Although the CCR3 antagonist did not decrease the number of eosinophils in lung tissues as assessed histologically, CCR3 antagonist prevented antigen-induced clustering of eosinophils along the nerves. Immunostaining revealed eotaxin in airway nerves and in cultured airway parasympathetic neurons from both guinea pigs and humans. Both IL-4 and IL-13 increased expression of eotaxin in cultured airway parasympathetic neurons as well as in human neuroblastoma cells. Thus, signaling via CCR3 mediates eosinophil recruitment to airway nerves and may be a prerequisite to blockade of inhibitory M2Rs by eosinophil major basic protein.
Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial
Authors: Amit M Oza, David Cibula, Ana Oaknin Benzaquen, Christopher Poole, Ron H J Mathijssen, Gabe S Sonke, Nicoletta Colombo, Jiří Špaček, Peter Vuylsteke, Holger Hirte, Sven Mahner, Marie Plante, Barbara Schmalfeldt, Helen Mackay, Jacqui Rowbottom, Elizabeth S Lowe, Brian Dougherty, J Carl Barrett, Michael Friedlander
Journal: The Lancet Oncology (2014)
Letter: Effective dosage of tricyclic antidepressants.
Authors: A Copper, S Montgomery, W H Lyle
Journal: BMJ (1975)

Keratoconjunctivitis Caused by AdenovirusType 19 SIR,-We were interested in the cases of adenovirus type 19 keratoconjunctivitis reported from Belgium and Holland by Dr. J. Desmyter and others (16 November, p. 406).Though a few strains of this virus have been isolated elsewhere in Britain during 1973-4, it was not until July 1974 that it was first detected in Scotland.The patient, a male anaesthetist aged 52 years, first developed photophobia and "gritty" discomfort of the right eye and five to six days later the left eye became affected.Ophthalmological examination confirmed the diagnosis of keratoconjunctivitis with deep scleral inflammation.A conjunctival swab was submitted for virological examination and meanwhile treatment with chloram- phenicol was instituted, with no effect.Though the episode lasted one month, the patient continued his normal duties throughout.An adenovirus, subsequently identified as type 19, was isolated in human amnion cell cultures.This appeared to be an isolated incident.There was no relevant history of recent travel abroad or contact with a similar case.However, this does raise the question whether anaesthetists may be at special risk from their proximity to the face and oronasal secretions of their patients.-Weare, etc.,
The New Antiepileptic Drugs
Authors: Suzette M. LaRoche, Sandra L. Helmers
Journal: JAMA (2004)

In the past decade, 8 new antiepileptic drugs have been approved for use in the United States, offering many new treatment options to patients with epilepsy. With expanding use of these newer agents, primary care clinicians are challenged with understanding the roles that each new agent plays in the treatment of patients with epilepsy as well as possible interactions with other pharmacological therapies. Each new medication provides a unique profile of pharmacokinetics, adverse effects, and mechanisms of action, making an appreciation of how these agents are best utilized even more difficult. Despite well-performed trials evaluating the safety and efficacy of specific antiepileptic drugs, the lack of head-to-head comparisons among them makes it difficult to endorse a single therapeutic regimen. Limited studies have compared the new antiepileptic drugs with more traditional medications and found similar efficacy but improved tolerability of the newer agents. There remains no well-established guidelines for choosing a particular antiepileptic drug or for choosing a newer agent over a traditional one. However, careful consideration of seizure type, patient comorbidities, and specific medication toxicities aids in prescribing the most appropriate medication. This article aims to familiarize the general practitioner with the appropriate roles and effective uses of the new antiepileptic drugs in specific clinical scenarios.
Randomised trial of early diet in preterm babies and later intelligence quotient
Authors: A Lucas, R Morley, T J Cole
Journal: BMJ (1998)

<h3>abstract</h3> <b>Objectives:</b> To determine whether perinatal nutrition influences cognitive function at 7 1/2 - 8 years in children born preterm. <b>Design:</b> Randomised, blinded nutritional intervention trial. Blinded follow up at 7 1/2 - 8 years. <b>Setting:</b> Intervention phase in two neonatal units; follow up in a clinic or school setting. <b>Subjects:</b> 424 preterm infants who weighed under 1850 g at birth; 360 of those who survived were tested at 7 1/2 - 8 years. <b>Interventions:</b> Standard infant formula versus nutrient enriched preterm formula randomly assigned as sole diet (trial A) or supplements to maternal milk (trial B) fed for a mean of 1 month. <b>Main outcome measures:</b> Intelligence quotient (IQ) at 7 1/2 - 8 years with abbreviated Weschler intelligence scale for children (revised). <b>Results:</b> There was a major sex difference in the impact of diet. At 7 1/2 - 8 years boys previously fed standard versus preterm formula as sole diet had a 12.2 point disadvantage (95% confidence interval 3.7 to 20.6; P&lt;0.01) in verbal IQ. In those with highest intakes of trial diets corresponding figures were 9.5 point disadvantage and 14.4 point disadvantage in overall IQ (1.2 to 17.7; P&lt;0.05) and verbal IQ (5.7 to 23.2; P&lt;0.01). Consequently, more infants fed term formula had low verbal IQ (&lt;85): 31% versus 14% for both sexes (P=0.02) and 47% versus 13% in boys P=0.009). There was a higher incidence of cerebral palsy in those fed term formula; exclusion of such children did not alter the findings. <b>Conclusions:</b> Preterm infants are vulnerable to suboptimal early nutrition in terms of their cognitive performance—notably, language based skills—at 7 1/2 - 8 years, when cognitive scores are highly predictive of adult ones. Our data on cerebral palsy generate a new hypothesis that suboptimal nutritional management during a critical or plastic early period of rapid brain growth could impair functional compensation in those sustaining an earlier brain insult. Cognitive function, notably in males, may be permanently impaired by suboptimal neonatal nutrition.
Tc-99m MDP Bone Scan Artefact Abdominal Soft Tissue Uptake Secondary to Subcutaneous Heparin Injection
Authors: Raymond B. Duong, David T. Volarich, Mariano Fernandez-Ulloa, Prasan J. Vasavada
Journal: Clinical Nuclear Medicine (1984)

DUONG, RAYMOND B. M.D.; VOLARICH, DAVID T. D.O.; FERNANDEZ-ULLOA, MARIANO M.D.; VASAVADA, PRASAN J. M.D. Author Information
Long-term survival after orthotopic and heterotopic cardiac transplantation.
Authors: D K Cooper, R G Charles, R C Fraser, W Beck, C N Barnard
Journal: BMJ (1980)

Five long-term survivors of heart transplantation were reinvestigated. Two patients had undergone orthotopic heart transplantation over 11 and 9 years earlier and constitute two of the world9s longest-surviving patients after this procedure. Three patients had undergone heterotopic heart transplantation (one left heart bypass alone and two biventricular bypass) four to six years earlier. Four of the five patients had had only one or no documented acute rejection episodes. Three had been given blood transfusions. None had had particularly good tissue matching in relation to the donor on HLA typing. All five patients were leading full and active lives. At review two patients had significant coronary artery disease, one severe, presumably due to chronic immune-complex deposition. Heart transplantation remains a major undertaking, but it can offer the patient many years of good-quality life.
Abstract 4623: Capsaicin represses transcriptional activity of β-catenin in human colorectal cancer cells
Authors: Seong-Ho Lee, Raphael L. Richardson, Seung J. Baek
Journal: Cancer Research (2011)

Abstract Capsaicin is a pungent ingredient in chili red peppers and has been linked to suppression of growth in various cancer cells. However, the underlying mechanism(s) by which capsaicin induces growth arrest and apoptosis of cancer cells is not completely understood. In the present study, we investigated whether capsaicin alters β-catenin signaling in human colorectal cancer cells in vitro. Exposure of human colorectal cancer cells to capsaicin suppressed cell proliferation. Transient transfection with β-catenin responsive reporter gene indicated that capsaicin suppressed transcriptional activity of β-catenin. Capsaicin treatment resulted in a decrease of intracellular β-catenin levels and a reduction of β-catenin transcripts. These results were confirmed by a reduced luciferase reporter activity driven by β-catenin promoter. In addition, capsaicin destabilized β-catenin through enhancement of proteosomal-dependent degradation. Western blot and immunoprecipitation studies indicated that capsaicin treatment disrupted interaction of TCF-4 and β-catenin and suppressed TCF-4 expression. This study identifies an important capsaicin-mediated pathway that contributes to anti-cancer activity of human colorectal cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4623. doi:10.1158/1538-7445.AM2011-4623
John Hunter the Observer
Authors: H. S. Souttar
Journal: BMJ (1949)

in 1728 at Long Calderwood, a small estate in Lanarkshire seven miles south of Glasgow, near the village of East Kilbride.He was the last of ten children, of whom seven survived childhood.Of them James, four- teen years his senior, entered medicine and joined his brother William in London, only to end from phthisis a career of brilliant promise at the age of 29.William, ten years the senior of John, was for five years a student at Glasgow, and at first was destined for the ministry.When he was 19, however, he joined Dr. William Cullen, who at the age of 27 had a busy practice at Hamilton, near Kil- bride.They must both have been young men of enterprise, for they arranged that in each winter one of them.should study medicine in Edinburgh or Glasgow while the other carried on the practice.In 1740 William Hunter attended Alexander Morris's lectures in Edinburgh, and in 1741, at the age of 23, he made up his mind to seek his fortune in London.Cullen went to Glasgow, where he became Professor of Medicine; but a few years later he moved to Edinburgh, occupying successively the Chairs of Chemistry, Institutes of Medicine, and the practice of Physic, and left a high
Decongestant efficacy of desloratadine in patients with seasonal allergic rhinitis
Authors: C Bachert
Journal: Allergy (2001)

Recent advances in experimental immunologic approaches to seasonal allergic rhinitis (SAR) have led to a shift in the concepts of its pathogenesis. The conventional view of SAR as a local response to inhaled allergens has largely given way to a new view of this disorder as a systemic condition with local tissue manifestations. This concept, together with an increasing recognition of specific mediators' distinct roles in driving the early‐ and late‐phase allergic responses, has opened multiple lines of therapeutic attack within the allergic cascade. Potent inhibition of inflammatory mediator release at distinct points in this cascade is conferred by desloratadine. In addition to the familiar range of SAR symptoms amenable to antihistamine therapy, desloratadine uniquely attenuates patient ratings of nasal congestion. This novel, nonsedating histamine H 1 ‐receptor antagonist is the only once‐daily antiallergic product with a consistent decongestant effect that begins within hours of the first morning dose and is sustained for the entire treatment period.