tbuckley/cabot-search huggingface dataset:
Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) gene products are regulated post-transcriptionally during rat cardiac development
Authors: A Ribadeau-Dumas
Journal: Cardiovascular Research (1999)

Objective: The Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) plays a major role in the contraction–relaxation cycle and is responsible for transporting calcium into the lumen of the sarcoplasmic reticulum. This study was performed to determine if the increase in SERCA2 messenger RNA (mRNA) abundance during the perinatal period is regulated transcriptionally. Methods: Transcriptional activity was determined by nuclear run-on assays and mRNA and protein abundances were determined during late fetal and early neonatal cardiac development in rat. Results: From nuclear run-on assays, SERCA2 gene transcription at 17/18 embryonic days (139±41 parts per million (ppm), n=7) did not differ from that at 20 neonatal days (139±37 ppm, n=6) after birth. No increase in transcriptional activity could be demonstrated during the time frame examined. In contrast, both alpha and beta myosin heavy chains showed significant changes in measured transcriptional activity. SERCA2 mRNA normalized to 18S RNA levels are very low in the fetus (9.8±1.9 to 13.4±4.9 arbitrary units (A.U.) from 17/18 to 19/20 embryonic days) and significantly increase from birth (15±3.8 A.U.) to reach a maximum at 20 days of age (29.1±9.5 to 48.3±7.0 in 15 to 20 neonatal days rats respectively). Similarly, SR Ca2+-ATPase protein levels are less abundant in the fetus (0.82±0.08 to 1.13±0.13 A.U./μg total protein) and reach a maximum at 15–20 neonatal days (3.08±0.58 to 2.98±0.17). Ca2+ uptake in the fetal heart is about one sixth the level seen in the adult, reaches the highest observed value at 5 days after birth (6.05±0.77 pmole Ca2+per μg/min) and remains relatively constant over the next 15 days. The activity increases even though phospholamban protein increases in abundance. Conclusions: Since the transcriptional activity of this gene is unchanged whereas the mRNA, protein abundance and activity increase, we conclude that the abundance of SERCA2 gene products is regulated primarily through post-transcriptional mechanisms during the perinatal period.
Reactive oxygen metabolites relax the lamb ductus arteriosus by stimulating prostaglandin production.
Authors: R I Clyman, O D Saugstad, F Mauray
Journal: Circulation Research (1989)

To determine whether oxygen metabolites can cause ductus relaxation, we used rings of fetal ductus obtained from 36 near-term lambs and measured the effects of the oxygen metabolites generated by the combination of hypoxanthine and xanthine oxidase. The oxygen metabolites produced by hypoxanthine plus xanthine oxidase caused relaxation of the ductus that was inhibited by catalase (hydrogen peroxide scavenger) but not by superoxide dismutase (superoxide anion scavenger). In addition, hypoxanthine plus xanthine oxidase produced a 14-fold increase in prostaglandin (PG) E2 production with only twofold increase in 6-keto-PGF1 alpha (the stable metabolite of PGI2). PGE2 is the most potent relaxant of the ductus arteriosus. The presence of either catalase or indomethacin blocked both the increase in prostaglandin production and the relaxation. We conclude that reactive oxygen metabolites relax the ductus arteriosus and oppose the normal constriction that occurs after birth. However, the vasoactive effects of reactive oxygen metabolites in the ductus appear to be mediated exclusively through the generation of PGE2.
Admissions Screening: Clinical Benefits
Authors: CHRISTOPHER C. KORVIN
Journal: Annals of Internal Medicine (1975)

One thousand patients admitted to a 575-bed general hospital during a 6-month period each underwent 20 chemical and hematologic tests. The potential clinical benefit was assessed. There were 2223 abnormal results found; 675 were predicted on clinical assessment, 1325 did not yield new diagnoses, and the remaining 223 led to 83 new diagnoses in 77 patients. On critical evaluation of the new diagnoses, none were unequivocally beneficial to the patient. Up to 30 patients might have benefited had these abnormal findings been followed up diligently, 39 others had findings or diagnoses of no lasting significance, and in 14 patients asymptomatic mild biochemical diabetes was discovered. Although screening may reveal many abnormal test results, the clinical benefits are not impressive.
BMA annual meeting: Children are being systematically failed through austerity measures, conference is told
Authors: G. Iacobucci
Journal: BMJ (2014)

The UK government must direct more resources for health and social care towards families and children who are being “disproportionately” affected by austerity measures and welfare changes, doctors have urged.

Delegates at the BMA’s annual representative meeting in Harrogate this week overwhelmingly backed a motion calling on the government to provide adequate resources for community and family support schemes; to increase investment in programmes …
Treatment of Relapsed Chronic Lymphocytic Leukemia by 72-Hour Continuous Infusion or 1-Hour Bolus Infusion of Flavopiridol: Results from Cancer and Leukemia Group B Study 19805
Authors: John C. Byrd, Bercedis L. Peterson, Janice Gabrilove, Olatoyosi M. Odenike, Michael R. Grever, Kanti Rai, Richard A. Larson
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Flavopiridol has in vitro activity in chronic lymphocytic leukemia (CLL) and promotes apoptosis independent of p53 function or prior fludarabine exposure. We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration. Patients and Methods: Patients with previously treated CLL were enrolled in two sequentially done phase II studies. Patients in the first trial received flavopiridol (50 mg/m2/d) as a continuous infusion (CI) for 72 hours every 2 weeks. Patients in the second trial received flavopiridol 50 mg/m2 as a 1-hour bolus (IVB) daily for 3 days repeated every 3 weeks. Patients received up to 12 (CI cohort) or 8 (IVB cohort) cycles of therapy. Results: Fifteen patients were enrolled in the 72-hour CI phase II trial; 6 (40%) had intermediate-risk (Rai stage I or II) and 9 (60%) had high-risk (Rai stage III and IV) stages. No responses were noted in this group; 27% had stable disease and 73% had progressive disease. Thirty-six patients were enrolled in the second IVB trial, with 13 (36%) having intermediate and 23 (64%) having high-risk disease. Four patients (11%) had partial responses, 19 (53%) had stable disease, and 13 (36%) had progressive disease. The progression-free survival for responders in the IVB trial was 3, 3, 9, and 19 months. The median progression-free survival was 2 months [95% confidence interval (95% CI), 1.8-3.8] for patients in the CI trial and 3 months (95% CI, 2.5-7.4) for the IVB trial. The median overall survival was 27 months (95% CI, 20-42) for the CI trial and 24 months (95% CI, 18-31) for the IVB trial. Toxicity was manageable and included mainly myelosuppression, infections, diarrhea, and fatigue. Conclusions: Flavopiridol has modest, schedule-dependent clinical activity in relapsed CLL and warrants future investigation utilizing alternative schedules of administration.
HCV quasispecies evolution: association with progression to end-stage liver disease in hemophiliacs infected with HCV or HCV/HIV
Authors: Hongxing Qin, Norah J. Shire, Erica D. Keenan, Susan D. Rouster, M. Elaine Eyster, James J. Goedert, Margaret James Koziel, Kenneth E. Sherman
Journal: Blood (2004)
COLD-AIR TREATMENT IN TETANUS.
Authors: W. J. McCRANN
Journal: JAMA (1904)

<h3>Patient.</h3> —F. McK., aged 10, was first seen Sept. 5, 1904. <h3>Examination.</h3> —His symptoms were those of tetanus and on examination we found a splinter in the bottom of the left foot. The history was that the splinter had been in the foot eight days. This was removed and tincture of iodin applied to the wound, which was suppurating slightly. <h3>Course of the Disease.</h3> —At this time and during the two following days the muscles of the neck, back and abdomen were rigid, respiration was difficult, moderate opisthotonos was present and he complained of pain in the head and stomach; convulsive movements appeared when he made an effort to move or talk. Two doses of anti-tetanic serum were given hypodermically and he was placed on full doses of chloral and bromids. The symptoms grew progressively worse during the first three days of our observation, when it was decided
A CASE OF PARALYSIS OF THE RECURRENT LARYNGEAL NERVEFROM ANEURISM OF THE ARCH OF THE AORTA.
Authors: HILL HASTINGS
Journal: JAMA (1905)

This case is reported in the interest of laryngology, because of the strong and positive light thrown on the diagnosis by an examination of the larynx. This led to the search for the physical signs of an aneurism of the aorta, which had been overlooked and which might not have been discovered for some time. The history of the case rather inclined toward tuberculosis of the lungs, with secondary laryngeal involvement. It was due to the latter complication that the case was referred for laryngeal examination and treatment. The radiograph of the chest was made to aid in confirming the diagnosis. <h3>Patient.</h3> —P. H., 43 years of age, was referred to me two months ago on account of hoarseness. His appearance and voice indicated tuberculosis of the lungs and larynx. The history given at the time was as follows. <h3>History.</h3> Hoarseness was first noticed five or
Intracellular ATP can regulate afferent arteriolar tone via ATP-sensitive K+ channels in the rabbit.
Authors: J N Lorenz, J Schnermann, F C Brosius, J P Briggs, P B Furspan
Journal: Journal of Clinical Investigation (1992)

Studies were performed to assess whether ATP-sensitive K+ (KATP) channels on rabbit preglomerular vessels can influence afferent arteriolar (AA) tone. K+ channels with a slope conductance of 258 +/- 13 (n = 7) pS and pronounced voltage dependence were demonstrated in excised patches from vascular smooth muscle cells of microdissected preglomerular segments. Channel activity was markedly reduced by 1 mM ATP and in a dose-dependent fashion by glibenclamide (10(-9) M to 10(-6) M), a specific antagonist of KATP channels. 10(-5) M diazoxide, a K+ channel opener, activated these channels in the presence of ATP, and this effect was also blocked by glibenclamide. To determine the role of these KATP channels in the control of vascular tone, diazoxide was tested on isolated perfused AA. After preconstriction from a control diameter of 13.1 +/- 1.1 to 3.5 +/- 2.1 microns with phenylephrine (PE), addition of 10(-5) M diazoxide dilated vessels to 11.2 +/- 0.7 microns, which was not different from control. Further addition of 10(-5) M glibenclamide reconstricted the vessels to 5.8 +/- 1.5 microns (n = 5; P less than 0.03). In support of its specificity for KATP channels, glibenclamide did not reverse verapamil induced dilation in a separate series of experiments. To determine whether intracellular ATP levels can effect AA tone, studies were conducted to test the effect of the glycolytic inhibitor 2-deoxy-D-glucose. After preconstriction from 13.4 +/- 3.2 to 7.7 +/- 1.3 microns with PE, bath glucose was replaced with 6 mM 2-deoxy-D-glucose. Within 10 min, the arteriole dilated to a mean value of 11.8 +/- 1.4 microns (n = 6; NS compared to control). Subsequent addition of 10(-5) M glibenclamide significantly reconstricted the vessels to a diameter of 8.6 +/- 0.5 micron (P less than 0.04). These data demonstrate that KATP channels are present on the preglomerular vasculature and that changes in intracellular ATP can directly influence afferent arteriolar tone via these channels.
Radiation Emergencies and the Practicing Physician
Authors: William R. Hendee
Journal: JAMA (1987)

Nuclear power and its risks have long been a contentious issue in this country. Advocates of the technology insist that the hazards are miniscule and that nuclear energy has the potential to provide an almost unlimited supply of electricity with little risk to individuals or the environment. Critics reply that the technology threatens the health of communities and even the survival of the human race. This polarization of viewpoints has prevented meaningful discussions between proponents and opponents. Planning for radiation emergencies is a topic for which there have been only sporadic attempts at dialogue. Some physicians and scientists concerned about their abilities to respond to radiation emergencies claim that their overtures to utility companies for information and discussion have been rebuffed with the statement that an event requiring major medical resources cannot occur. In contrast, representatives of utility companies say they are willing to discuss the need to plan for
Cyanosis with Deficiency of the Interventricular Septum
Authors: J. Johnston
Journal: BMJ (1872)

THE subject of the present remarks, J. Thompson, aged 9, the son of healthy parents, was apparently in perfect health until seven years old.He had never suffered from rheumatism in any form, nor was there any history of shock or violent exertion.About two years since, he complained, for the first time, of dyspncea, pain across the chest, and dizziness.lIe then had the first of a series of epileptic fits, and from that time gradually became cyanotic.
Sitting Posture of Children
Authors: David E. Larson
Journal: JAMA (1976)

To the Editor.—  I certainly agree that television has a potentially harmful influence on our children (234:1002, 1975), but what about the harmful influence of showing a child sitting in a potentially harmful position on the cover of a national medical magazine?  The boy in front of the fireplace is sitting on his legs, thereby producing abnormal forces on his hips. The right leg is in the so-called W position that definitely contributes to excessive femoral anteversion. A pigeon-toe gait, most particularly in the right lower extremity, will develop in a child who sits in this position habitually.  Physicians should constantly be urging parents to make their children sit with their legs out in front of them or folded in front of them Indian style. It is also helpful to alert babysitters, nursery school teachers, and relatives to help encourage and remind children to have proper sitting patterns for their
Administration of Sulfonylureas Can Increase Glucose-Induced Insulin Secretion for Decades in Patients With Maturity-Onset Diabetes of the Young
Authors: Stefan S Fajans, Morton B Brown
Journal: Diabetes Care (1993)

Objective— To ascertain whether the effect of sulfonylureas on glucose-mediated insulin release persists for years to decades in patients with maturity-onset diabetes of the young. Research Design and Methods— The effect of sulfonylurea treatment on glucose-induced insulin secretion was ascertained prospectively for up to 33 yr in 12 diabetic patients of the maturity-onset diabetes of the young RW pedigree, who are genetically homogeneous because they share DNA markers on chromosome 20q. In 7 of these patients, paired glucose tolerance tests, given while the patients were on and off sulfonylureas, were performed after 7–31 yr. Results— Glucose-induced insulin secretion showed an average increase of 68% in diabetic patients who remained responsive to chlorpropamide after having been on and off the drug for decades. In most patients, however, glucose-induced insulin secretion declines over time (1–4%/yr). Some patients become unresponsive to sulfonylureas after 3–25 yr and then have very small or no increases in glucose-induced insulin secretion and require treatment with insulin to normalize fasting hyperglycemia. Conclusions— Increase in glucose-induced insulin secretion remains the most important mechanism of the action of sulfonylureas during long-term administration.
Technical Appendix: Cost-effectiveness of Vitamin Therapy for Age-Related Macular Degeneration
Authors: David B. Rein, Jinan B. Saaddine, John S. Wittenborn, Kathleen Wirth, Thomas J. Hoerger, K.M. Venkat Narayan, Traci Clemons, Stephen W. Sorensen
Journal: Ophthalmology (2007)
Incidence of patients at high risk of sudden death among patients referred for the suspicion of a brugada-syndrome: a prospective study in 35 consecutive patients with Brugada-like ECG changes
Authors: Constanze M. Echternach, Martin Borggrefe, Susanne Spehl, Ayse Bilbal, Michael Junker, Juergen Kuschyk, Tim Süselbeck, Karl K. Haase, Christian Wolpert
Journal: Journal of the American College of Cardiology (2002)
Spontaneous rupture of the anterior cruciate ligament after anabolic steroids.
Authors: B J Freeman, G D Rooker
Journal: British Journal of Sports Medicine (1995)

Anabolic steroids remain popular among body builders and power athletes despite numerous warning about their side effects. A case of spontaneous rupture of the anterior cruciate ligament is reported in a bodybuilder taking steroids. While there are many published reports of tendon rupture associated with steroid intake, the authors could find no report relating to ligament disruption.
Twenty-First Century Behavioral Medicine: A Context for Empowering Clinicians and Patients With Diabetes
Authors: David G. Marrero, Jamy Ard, Alan M. Delamater, Virginia Peragallo-Dittko, Elizabeth J. Mayer-Davis, Robin Nwankwo, Edwin B. Fisher
Journal: Diabetes Care (2013)

In the past decades, the sophistication of treatments for diabetes has increased dramatically, and evidence for effective interventions has proliferated. As a result, it is now possible to achieve excellent glucose control and reduce the risk of many of the complications associated with the disease. Despite these advances, however, many people with diabetes have less than optimal metabolic control and continue to suffer from preventable complications. The gap between optimal evidence-based medicine and actual practice can be great, dependent not only on the ability of the clinician to make changes in practice patterns but also on the central role of the patient in implementing optimal management plans in daily life. With recognition of the centrality of patients’ actions to achieve optimal outcomes must come awareness that those actions reflect much more than simple “self-control.” In addition to individual characteristics, the environment in which behaviors are enacted has great influence, from family eating patterns to the design of neighborhoods to workplace and national health policies. For patients and clinicians, these factors create the context or environment in which behaviors are enacted.

Diabetes provides a prime example of this fundamental interaction of individual characteristics with the ecological or contextual factors. For example, Pima Indians living in the U.S. have the highest prevalence of type 2 diabetes of any population in the world, yet Pimas living traditional lifestyles in Mexico have relatively low levels of diabetes. Ample evidence links genetics to diabetes within the Pima population, but exposure to an obesogenic environment is critical to expression of this very strong genetic propensity (1).

This interplay between the individual and the context in which he or she behaves is commonly cited in discussions of personal health choices and health and social policies. These perspectives have shifted in …
Book: The Expressiveness of the Body and the Divergence of Greek and Chinese Medicine
Authors: W F Bynum
Journal: BMJ (2000)

Shigehisa Kuriyama Zone Books, £20.50, pp 340 ISBN 0 942299 88 4 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Have you ever wondered why figures in Chinese medical writings are smooth skinned and plump, whereas Greek sculpture commonly depicted taut muscle men, their biceps and sterno-cleido-mastoids sharply outlined? Why Confucius always sports an ample belly, but the most powerful Versalian image is a lean corpse, its skin stripped away to expose its carefully dissected muscles? Why, in the West, taking the pulse is a shadowy remnant of a once vital diagnostic procedure, and why it … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
The Distribution of Refractory Periods Influences the Dynamics of Ventricular Fibrillation
Authors: Bum-Rak Choi, Tong Liu, Guy Salama
Journal: Circulation Research (2001)

The spatial and dynamic properties of ventricular fibrillation (VF) may be random or related to cellular electrical properties of the normal heart. Local activation intervals (AIs) in VF may depend on the local refractory period (RP), and sustained VF may require a steep action potential (AP) restitution curve. In guinea pig hearts, AP durations (APDs) and RPs on the epicardium are shorter at the apex and progressively longer toward the base, producing gradients of RPs that may influence the spatial organization of VF. In the present study, the influence of APDs on VF dynamics is investigated in perfused guinea pig hearts stained with a voltage-sensitive dye by comparing APD gradients to the dynamics of VF elicited by burst pacing. In VF, AIs had no clear periodicity, but average AIs were shorter at the apex (57.5+/-8.1 ms) than the base (76.1+/-1.5 ms, n=6, P<0.05) and had gradients similar to APD gradients (correlation coefficient 0.71+/-0.04). Analysis of local velocity vectors showed no preferential directions, and fast Fourier transform (FFT) power spectra were broad (10 to 24 Hz) with multiple peaks (n=6). However, the selective inhibition of delayed K(+) rectifying currents, I(Kr) (E4031; 0.5 micromol/L, n=3), shifted FFT spectra from complex to a lower dominant frequency (10 Hz) and altered repolarization but retained the correlation between mean AIs and RPs. Thus, VF dynamics are consistent with a multiple wave-make and wave-break mechanism, and the local RP influences VF dynamics by limiting the range of VF frequencies and AIs at each site. The full text of this article is available at http://www.circresaha.org.