tbuckley/cabot-search huggingface dataset:
Oral cholera vaccine well tolerated.
Authors: P Barrett, P Clarke, S Cryz
Journal: BMJ (1993)

the former Yugoslavia-and particularly besieged areas-to offer help with the specific surgical and medical problems.Humanitarian Aid with Medical Deployment is now organising specialist surgical teams to visit Bosnia for periods of seven days to work on specific problems such as nerve injuries, joint contractures, and complex fractures that have failed to unite.This plan should be pursued during the winter months and volunteers, either individuals or teams, are very welcome.Professor Dudley was told in Vietnam that his teams would "be remembered in the marketplace," and we can assure any volunteer that this was exactly our experience in Bosnia.Volunteers should not expect to make a large contribution, but they will inestimably raise the morale of the local medical professionals and their patients.
Plasma Clearance of dl-β-H3-Norepinephrine in Normal Human Subjects and Patients with Essential Hypertension*
Authors: Stanley E. Gitlow, Milton Mendlowitz, Elizabeth Kruk Wilk, Sherwin Wilk, Robert L. Wolf, Nosrat E. Naftchi
Journal: Journal of Clinical Investigation (1964)

In 1936 hemodynamic measurements in patients with essential hypertension suggested the pres- ence of a functional increase in peripheral vaso- constriction producing an abnormally high periph- eral resistance to blood flow (1).The concept that physiologic degrees of vasoconstriction were main- tained by the adrenergic neurohumor, norepineph- rine (NE), was proposed almost simultaneously (2), but it was nearly 10 years later that von Euler (3, 4), Holtz, Credner, and Kroneberg ( 5), and others demonstrated that NE was normally present in and released by mammalian sympathetic nerves.Within a year, Goldenberg and co-work- ers (6) suggested that essential hypertension might be caused by the simple overproduction of NE.This neurohumoral theory underwent repeated evaluation, first by the measurement of NE in urine (7, 8) and plasma (9), and later by the assay in urine of the major NE catabolites, vanillylman- delic acid (VMA) (10), normetanephrine (NM) (11), and 3-methoxy, 4-hydroxyphenyl glycol (NMG) (12).Since no clear-cut evidence of NE overproduction could be found (8-10), and since physiologic studies suggested that essential hypertension was associated with abnormally increased vascular reactivity to infused NE (13), it seemed possible that the disease might be causally related to ab- normal metabolic handling of that NE produced in normal quantities by these patients.To evalu- ate the metabolism of a substance that underwent degradation within moments of its administration and which produced an intense physiologic effect in nanogram amounts, a tracer compound of high
Inhaled Corticosteroids in Chronic Obstructive Pulmonary Disease
Authors: Victor A. Kiri, Neil B. Pride, Joan B. Soriano, Jørgen Vestbo
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Recent cohort studies in chronic obstructive pulmonary disease (COPD) have questioned the validity of previously reported associations between inhaled corticosteroids (ICS) and reductions in mortality and rehospitalization in observational studies. Using time-dependent versions of statistical survival models, these studies have suggested immortal time bias as responsible for the proposed beneficial association.We explored the extent of this bias in a study of patients with COPD monitored for a year from COPD discharge with two designs free of any immortal time bias in the General Practice Research Database in the United Kingdom.In Design 1, we used only patients whose treatment status was defined on the same day of discharge to obtain a matched cohort based on propensity scores, which were derived from the patient-level baseline characteristics. In Design 2, we identified all in the study cohort who experienced death or rehospitalization and then matched each case to up to four noncases by randomly sampling from the cohort risk sets without regard to treatment status.The propensity scores matched cohort analysis of 786 patients without a wait time found a significant risk reduction associated with use of ICS: hazard ratio, 0.69 (95% confidence interval, 0.52-0.93). The matched nested case-control analysis of 2,222 patients, designed without regard to exposure status and hence free of immortal time bias, gave a similar association with exposure to ICS in the last 6-month period: hazard ratio, 0.71 (0.56-0.90).We conclude that immortal time bias cannot account for the risk reduction associated with ICS exposure in observational studies.
Legislative Challenges to School Immunization Mandates, 2009-2012
Authors: Saad B. Omer, Diane Peterson, Eileen A. Curran, Alan Hinman, Walter A. Orenstein
Journal: JAMA (2014)

School immunization mandates, implemented through state-level legislation, have played an important role in maintaining high immunization coverage in the United States. Immunization mandates permit exemptions that vary from state to state in terms of type of exemption (eg, religious, personal belief, medical), and administrative ease of obtaining these exemptions. Certain types of exemptions (especially personal belief exemptions) and the ease of obtaining them are predictive of high rates of vaccine exemptions and increased disease risk among exemptors themselves and in the communities in which they reside.1,2

Legislation has been proposed in recent years to modify exemptions to school immunization requirements. We analyzed such legislation at the state level.
Adverse Reactions to Intravascular Administration of Contrast Media
Authors: Elliott C. Lasser
Journal: Allergy (1981)

Adverse reactions to intravascular administration of contrast media, while low in incidence, merit serious consideration in view of increased utilization of these substances all over the world. Evidence for involvement of soluble mediators, antibody‐antigen reactions, psycho‐genie factors, and the acute activation systems, is reviewed. As a group, the pre‐contrast challenge plasmas of reactors are characterized by slightly diminished concentrations of C≲‐esterase inhibitor and total hemolytic complement, and by an accelerated rate of conversion of prekallikrein to kallikrein on exposure to contact activators. The role of intravenous pretesting and pretreatment is considered. A rationale for pretreatment with adrenocorticosteroids is presented.
Discordance between Meta-analyses and Large-Scale Randomized, Controlled Trials: Examples from the Management of Acute Myocardial Infarction
Authors: Steven Borzak
Journal: Annals of Internal Medicine (1995)

Clinicians making treatment decisions are faced with ever-growing numbers of therapies, each supported by different types of clinical data. By bringing together large amounts of data, meta-analysis has emerged as a useful tool for generating hypotheses with which to plan definitive trials, and it has also been recommended as a basis for decision making in the absence of definitive trials. In several instances, early meta-analyses have provided evidence of efficacy that was subsequently confirmed. However, in other instances, the results of initial meta-analyses have disagreed with the results of subsequent large-scale trials. Nitrate and magnesium therapy for acute myocardial infarction are two contemporary examples of treatments about which hypothesis-generating meta-analyses and subsequent large trials have disagreed. We review the issues surrounding the interpretation of meta-analyses in these cases, and we suggest that the appropriate use of meta-analyses in clinical decision making be carefully placed in the context of a review of pathophysiologic principles and the results of basic laboratory research and individual trials.
The Niacin/Butyrate Receptor GPR109A Suppresses Mammary Tumorigenesis by Inhibiting Cell Survival
Authors: Selvakumar Elangovan, Rajneesh Pathania, Sabarish Ramachandran, Sudha Ananth, Ravi N. Padia, Ling Lan, Nagendra Singh, Pamela M. Martin, Lesleyann Hawthorn, Puttur D. Prasad, Vadivel Ganapathy, Muthusamy Thangaraju
Journal: Cancer Research (2013)

Abstract GPR109A, a G-protein–coupled receptor, is activated by niacin and butyrate. Upon activation in colonocytes, GPR109A potentiates anti-inflammatory pathways, induces apoptosis, and protects against inflammation-induced colon cancer. In contrast, GPR109A activation in keratinocytes induces flushing by activation of Cox-2–dependent inflammatory signaling, and the receptor expression is upregulated in human epidermoid carcinoma. Thus, depending on the cellular context and tissue, GPR109A functions either as a tumor suppressor or a tumor promoter. However, the expression status and the functional implications of this receptor in the mammary epithelium are not known. Here, we show that GPR109A is expressed in normal mammary tissue and, irrespective of the hormone receptor status, its expression is silenced in human primary breast tumor tissues, breast cancer cell lines, and in tumor tissues of three different murine mammary tumor models. Functional expression of this receptor in human breast cancer cell lines decreases cyclic AMP production, induces apoptosis, and blocks colony formation and mammary tumor growth. Transcriptome analysis revealed that GPR109A activation inhibits genes, which are involved in cell survival and antiapoptotic signaling, in human breast cancer cells. In addition, deletion of Gpr109a in mice increased tumor incidence and triggered early onset of mammary tumorigenesis with increased lung metastasis in MMTV-Neu mouse model of spontaneous breast cancer. These findings suggest that GPR109A is a tumor suppressor in mammary gland and that pharmacologic induction of this gene in tumor tissues followed by its activation with agonists could be an effective therapeutic strategy to treat breast cancer. Cancer Res; 74(4); 1166–78. ©2013 AACR.
The Journal Itself.
Authors: John A. Murphy
Journal: JAMA (1896)

Cincinnati, June 5, 1896. <h3>To the Editor:</h3> —I enclose to you my ballot, as also my check for $5 for yearly dues. Now, my dear Doctor, I want to thank you for your distinguished services as Editor of theJournal. I think it ranks with the journals of the East. The tone of theJournalis high. It firmly supports the Code. In my opinion, it will grow and grow, and show the world that no section can control the Western and Southern profession. Wishing you and theJournalall success, I am Yours truly,
The Drug Trial: Nancy Olivieri and the Science Scandal that Rocked the Hospital for Sick Children
Authors: Christopher Martyn
Journal: BMJ (2005)

T he facts go something like this. In 1996 Nancy Olivieri, a haematologist working at the Hospital for Sick Children in Toronto, came to believe that an experimental iron chelating drug (deferiprone) that she was trialling in patients with thalassaemia was losing efficacy and causing serious adverse effects. Apotex, the company that made the drug and that was partly funding the trial, disagreed. When Olivieri indicated that she intended to inform participants of her concerns, Apotex terminated the trials and withdrew financial support. They invoked a confidentiality agreement in the research contract and threatened legal action if she made the findings public. Undeterred, Olivieri presented her results at a scientific meeting and submitted them for publication.

> Shuchman retells the story from a worm's eye view, dwelling on the personalities involved, what they said about each other, who was sleeping with whom 

Events after the dispute between Olivieri and Apotex showed deep divisions and personal …
Maternal allergy modulates cord blood hematopoietic progenitor Toll-like receptor expression and function
Authors: Pia Reece, Amudhinie Thanendran, Lynn Crawford, Meri K. Tulic, Lehana Thabane, Susan L. Prescott, Roma Sehmi, Judah A. Denburg
Journal: Journal of Allergy and Clinical Immunology (2010)
Ganglionic Mechanisms Contribute to Diminished Vagal Control in Heart Failure
Authors: Steve Bibevski, Mark E. Dunlap
Journal: Circulation (1999)

Previous work has shown that spontaneous and stimulated vagal activity is diminished in heart failure (HF) despite upregulation of functional postsynaptic cholinergic mechanisms. We therefore examined function of the postganglionic neuron in the paced canine model of HF as a possible site for diminished control.We measured sinus cycle length changes in response to electrical stimulation of preganglionic and postganglionic parasympathetic neurons innervating the sinoatrial node in control and HF dogs (both, n=8). Cervical vagus stimulation (preganglionic) demonstrated attenuated responses in the HF group at all levels of stimulation (P<0.05). Stimulation of the right atrial fat pad, containing both postganglionic nerves and terminals of preganglionic neurons, showed no such difference between control and HF (200+/-25 versus 192+/-18 ms). To ensure that preganglionic input and different levels of baseline sympathetic activity did not contribute to the group difference, similar stimulations were done in the presence of ganglionic and beta-adrenergic blockade. Under these conditions, postganglionic stimulation showed smaller changes in sinus cycle length, but the HF group response remained significantly higher than in controls (76+/-10 versus 20+/-2 ms; P<0. 01), indicating that the difference was independent of preganglionic input and sympathetic activity.A component of attenuated parasympathetic control in HF is located within the peripheral efferent limb. This defect is located within the parasympathetic ganglion. Future work should be focused on determining mechanisms of attenuated ganglionic transmission so that means targeted at restoring vagal activity can be developed.
Minimizing the non-specific binding of nanoparticles to the brain enables active targeting of Fn14-positive glioblastoma cells
Authors: Craig S. Schneider, Jimena G. Perez, Emily Cheng, Clark Zhang, Panagiotis Mastorakos, Justin Hanes, Jeffrey A. Winkles, Graeme F. Woodworth, Anthony J. Kim
Journal: Biomaterials (2014)
Fatal Congestive Heart Failure Associated with Cardiac Enlargement of Unexplained Origin
Authors: RICHARD FRANCE, CLIFFORD W. ATHERTON, WILLIAM L. ALSOBROOK
Journal: Circulation (1956)

A case of progressive cardiac enlargement of unknown cause in a 22-year-old man is reported. Death from congestive failure occurred 18 months after the onset of symptoms. Postmortem examination showed only cardiac hypertrophy and dilatation as an explanation for the congestive failure.
Activation of a TRPC3-Dependent Cation Current through the Neurotrophin BDNF
Authors: Hong-Sheng Li, Xian-Zhong Shawn Xu, Craig Montell
Journal: Neuron (1999)

Nonvoltage-gated cation currents, which are activated following stimulation of phospholipase C (PLC), appear to be major modes for Ca2+ and Na+ entry in mammalian cells. The TRPC channels may mediate some of these conductances since their expression in vitro leads to PLC-dependent cation influx. We found that the TRPC3 protein was highly enriched in neurons of the central nervous system (CNS). The temporal and spatial distribution of TRPC3 paralleled that of the neurotrophin receptor TrkB. Activation of TrkB by brain-derived nerve growth factor (BDNF) led to production of a PLC-dependent, nonselective cation conductance in pontine neurons. Evidence is provided that TRPC3 contributes to this current in vivo. Thus, activation of TrkB and PLC leads to a TRPC3-dependent cation influx in CNS neurons.
Umbilical Vein Demonstration During Liver Imaging of A Cirrhotic Patient
Authors: CHARLES A. ROGERS, GARY McLELLAN
Journal: Clinical Nuclear Medicine (1982)

Hepatofugal flow in a patent umbilical vein was demonstrated during routine hepatic scintiangiography for evaluation of a hepatic lesion associated with cirrhosis. This finding, probably specific for portal hypertension, could be used diagnostically and in the evaluation of candidates for corrective surgery.
Australia opts to label drugs developed through stem cell research
Authors: B. Burton
Journal: BMJ (2003)

The Australian government will require that drug manufacturers disclose whether material from human embryos or embryonic stem cells was used in the manufacture or testing of drugs registered after 1 July 2004.

The change is the result of lobbying by Senator Brian Harradine, a staunch Catholic who persuaded the Minister for Health, Kay Patterson, to require that information on use of embryonic material be included in literature for doctors and in product information sheets accompanying medicines.

In the parliamentary debate late last year on legislation authorising research using human embryos and stem cells, Senator Patterson argued …
Essentials of Neurosurgery
Authors: John E. Adams
Journal: JAMA (1981)

This text is specifically oriented toward a readership of students, house officers, and primary care physicians. One might raise the question, as has been done, whether a neurosurgical text is relevant for this segment of the profession. The author is clearly aware of this question, but nevertheless the book suffers from the inclusion of many primarily nonneurosurgical conditions. Regarding those subjects, described as "common neurologic syndromes," ischemic cerebrovascular disease, etc, the reader would probably be better served by recourse to standard neurological texts for a more thorough examination in greater depth. The same criticism can be leveled at the chapter on epilepsy in which its neurological aspects are rather superficially treated. In a neurosurgical text, the emphasis should rest more on the areas in which neurosurgical treatment is indicated and appropriate. Properly, little emphasis is placed on neurosurgical techniques. The chapters are arranged in an orthodox fashion, beginning with neurological
Making the Investigational Oncology Pipeline More Efficient and Effective: Are We Headed in the Right Direction?
Authors: Patricia M. LoRusso, Aparna B. Anderson, Scott A. Boerner, Steven D. Averbuch
Journal: Clinical Cancer Research (2010)

Abstract Advances in our knowledge of the molecular mechanisms involved in cancer biology have contributed to an increase in novel target-specific oncology therapeutics. Unfortunately, clinical development of new drugs is an expensive and slow process, and the patient and financial resources needed to study the vast number of potential therapies are limited, requiring novel approaches to clinical trial design and patient recruitment. In addition, traditional efficacy endpoints may not be adequate to fully determine the therapeutic worth of the new classes of targeted agents. In this new era of drug development, it has become increasingly clear that new clinical trial design paradigms that examine nontraditional endpoints have become necessary to assist in prioritizing the development of the most promising agents. It is also vital that individual patient management be considered, and the subpopulations of patients most likely to derive benefit or experience harm from a new therapy be identified as early as possible. Phase I and II clinical trials allow investigators doing clinical research the opportunity to define these critical endpoints and subpopulations early on, before conducting large-scale randomized phase III clinical trials, which require an abundance of financial and patient resources. Clin Cancer Res; 16(24); 5956–62. ©2010 AACR.
Prevalence of Hearing Loss Among Children 6 to 19 Years of Age
Authors: Amanda Sue Niskar, Stephanie M. Kieszak, Alice Holmes, Emilio Esteban, Carol Rubin, Debra J. Brody
Journal: JAMA (1998)

Context.-Hearing loss in children influences the development of communication and behavioral skills, but few studies in the United States have used pure-tone audiometry to derive hearing loss prevalence estimates for children.Objective.-Todescribe the prevalence of hearing loss among US children by sociodemographic characteristics, reported hearing loss, and audiometric screening factors.Design.-National population-based cross-sectional survey with an in-person interview and audiometric testing at 0.5 to 8 kHz.Setting/Participants.-A total of 6166 children aged 6 to 19 years completed audiometry in the mobile examination center of the Third National Health and Nutrition Examination Survey conducted between 1988 and 1994.Main Outcome Measure.-Hearingloss, defined as audiometric threshold values of at least 16-dB hearing level based on a low or high pure-tone average.Results.-A total of 14.9% of children had low-frequency or high-frequency hearing loss of at least 16-dB hearing level, 7.1% had low-frequency hearing loss of at least 16-dB hearing level, and 12.7% had high-frequency hearing loss of at least 16-dB hearing level.Most hearing loss was unilateral and slight in severity (16to 25-dB hearing level).Of those with measured hearing loss, 10.8% were reported to have current hearing loss during the interview.Conclusions.-Thisanalysis indicates that 14.9% of US children have lowfrequency or high-frequency hearing loss of at least 16-dB hearing level in 1 or both ears.Among children in elementary, middle, and high school, audiometric screening should include low-frequency and high-frequency testing to detect hearing loss.
Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer
Authors: Matthew J. Resnick, Tatsuki Koyama, Kang-Hsien Fan, Peter C. Albertsen, Michael Goodman, Ann S. Hamilton, Richard M. Hoffman, Arnold L. Potosky, Janet L. Stanford, Antoinette M. Stroup, R. Lawrence Van Horn, David F. Penson
Journal: New England Journal of Medicine (2013)

The purpose of this analysis was to compare long-term urinary, bowel, and sexual function after radical prostatectomy or external-beam radiation therapy.
Quality of life after myocardial infarction: effect of long term metoprolol on mortality and morbidity.
Authors: G Olsson, J Lubsen, G A van Es, N Rehnqvist
Journal: BMJ (1986)

A double blind randomised study of 154 patients with myocardial infarction assigned to metoprolol (100 mg twice daily) and 147 assigned to placebo compared the effects of treatment in relation to health state over three years. Health state was evaluated by a new method based on the average number of days spent in each of seven mutually exclusive categories of health. The scale took into account death, history of serious complications, functional state, and side effects of treatment. Of the maximum attainable 1095 days alive during the three years patients given metoprolol attained 992 days and those given placebo 964 days. During the period alive the metoprolol treated group spent an average of 278 days in an optimal functional state as compared with 176 days for the placebo treated group. This included 221 and 156 days respectively in a completely asymptomatic state (that is, without either cardiac symptoms or side effects of treatment). The time spent with a serious non-fatal complication was shortened by 56 days in the metoprolol group. The overall differences between the groups were statistically significant (p = 0.03). Aside from bringing an improved quality of life after myocardial infarction, metoprolol may add up to one month to life expectancy for three years of treatment.
Single-Dose Therapy for Cystitis
Authors: Stephen A. Lerner
Journal: JAMA (1982)

Cystitis afflicts about 20% of women at least once in their lifetime.<sup>1</sup>Although this infection is generally treated with antibiotics, in some cases it may resolve spontaneously.<sup>2</sup>Therefore, courses of antimicrobial treatment shorter than the conventional seven to ten days, down to a single dose, have been investigated as a means of reducing the cost and side effects of treatment of this common infection. In this issue ofThe Journal(p 1839), Buckwold and co-workers extend a series of studies that report high rates of cure of urinary tract infection in women treated with single doses of antimicrobial agents that are excreted and concentrated in urine. Despite the ease of clearing of bacteria from the urine initially with antimicrobial therapy to which the infecting pathogen is susceptible, some women are prone to relapse after single-dose treatment, or even after conventional therapy.<sup>3</sup>The current study and some of the