tbuckley/cabot-search huggingface dataset:
There are ethical issues in ophthalmology
Authors: M P Clarke
Journal: BMJ (1999)

Some years ago my medical school introduced proposals for a new curriculum for undergraduate medical teaching. More time was required for subjects such as medical ethics, and specialties like ophthalmology were identified as surplus to requirements.

The ophthalmologists held a meeting and decided that the proposal to drop ophthalmology from the curriculum was bad news for the quality of future referrals and recruitment into the specialty. Something had to be done and everyone else took a backward step. While I was organising the week long ophthalmology attachment for the new curriculum, I received a letter from the organiser of ethics teaching. Would I like to incorporate some ethics teaching into the ophthalmology attachment? No thanks, I replied, and anyway one of the attractions of ophthalmology was its moral simplicity. Acute red eyes, cataract surgery: no ethical …
Electrolyte and Water Excretion in Arterial Hypertension
Authors: WILLIAM HOLLANDER, WALTER E. JUDSON
Journal: Circulation (1958)

The increased capacity of hypertensive subjects to excrete sodium is frequently reduced by effective antihypertensive drug treatment. This reduction in sodium excretion is not necessarily associated with changes in renal hemodynamic function or resting sodium excretion. It appears to result from an alteration in renal tubular activity. The findings suggest that the arterial pressure per se may operate to control sodium excretion. They also are consistent with the hypothesis that certain disturbances in sodium excretion in arterial hypertension may be the result and not necessarily the cause of an elevated blood pressure.
Anti-inflammatory Agents and Allergen-induced β<sub>2</sub>-Receptor Dysfunction in Isolated Human Bronchi
Authors: PINGFANG SONG, EMANUELE CRIMI, MANLIO MILANESE, JIE DUAN, KAI REHDER, VITO BRUSASCO
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Antigen challenge causes β2-adrenoceptor dysfunction in sensitized human bronchi (Am. J. Respir. Crit. Care Med. 1997;155:1230–1234). This study investigated whether the dysfunction can be prevented by anti-inflammatory agents. Human bronchial rings (2 to 4 mm) from surgery were passively sensitized to house dust mite and challenged (1) with allergen only, (2) with allergen plus indomethacin (10− 5 M), (3) with allergen plus nedocromil sodium (10− 7 M to 10− 5 M), (4) with allergen plus the H1-receptor antagonist cetirizine (10− 7 M to 10− 5 M), and (5) with allergen plus the peptido-leukotriene receptor antagonist iralukast (10− 7 M to 10− 5 M). Rings were first contracted with 10− 6 M carbachol and then relaxed with salbutamol (10− 9 M to 10− 4 M). The concentration–relaxation curve to salbutamol was shifted significantly to the right in the rings challenged with allergen only compared with control rings. In the rings challenged with allergen plus nedocromil sodium (10− 6 M and 10− 5 M) or iralukast (10− 6 M and 10− 5 M) the concentration–relaxation curves to salbutamol were significantly shifted to the left compared with rings challenged in saline alone, suggesting a protective effect against β2-adrenoceptor dysfunction. Neither allergen plus cetirizine nor allergen plus indomethacin shifted significantly the concentration–relaxation curves to salbutamol compared with rings challenged in saline alone. We conclude that the release of peptido-leukotrienes may play a significant role in causing the allergen-induced β2-receptor dysfunction in passively sensitized human bronchi.
1154-91 Cariporide but not epinephrine prevents ischemic contracture during closed-chest resuscitation
Authors: Vasundhara Vidyarthi, Atul Trivedi, Prabhakaran P Gopalakrishnan, Iyad M Ayoub, Julieta D Kolarova, Maida A Sehgal, Hanumant Deshmukh, Raúl J Gazmuri
Journal: Journal of the American College of Cardiology (2004)
MORTALITY IN CONGENITAL HEART DISEASE; ARE GOVERNMENTAL REGISTRIES RELIABLE FOR CAUSE OF DEATH?
Authors: A.C. Zomer, Cuno S.P.M. Uiterwaal, Enno T. van der Velde, Jan G.P. Tijssen, Edwin C.M. Mariman, Carianne L. Verheugt, Petronella G. Pieper, Folkert J. Meiboom, Diederick E. Grobbee, Barbara J.M. Mulder
Journal: Journal of the American College of Cardiology (2010)
Abstract 1348: The discovery of novel inhibitors that downregulate human thymidylate synthase
Authors: Jayanthi Repalli, James Chapman, Campbell McInnes, Sondra H. Berger
Journal: Cancer Research (2011)

Abstract Inhibitors of the enzyme thymidylate synthase (TS) are typically used as anti-cancer drugs to limit the growth of cancer cells. These inhibitors deplete TTP which is essential for DNA replication and repair. The enzyme in humans is postulated to undergo conformational switching between active and inactive forms. We are testing the hypothesis that stabilization of the inactive conformation will lead to increased turnover of hTS. Stabilization of hTS to degradation is observed after exposure to TS inhibitors in clinical use, which are active site-targeted. X-ray crystallographic studies of 1,3-propanediphosphonic acid (PDPA) bound to hTS led to the prediction that PDPA stabilizes the inactive conformation. Furthermore, PDPA exhibited competitive-noncompetitive behavior in TS catalytic reactions, consistent with allosteric inhibition. A cell-permeable isostere of PDPA inhibited hTS in catalytic assays, inhibited cell proliferation in a thymidine-dependent manner, and induced down regulation of hTS in cultivated cells. This is the first TS inhibitor to decrease the stability of hTS to degradation. To identify lead compounds that bind to the inactive conformation, molecular docking and structure-based virtual screening techniques were applied. Putative interaction sites were obtained from crystal structures of liganded hTS (with PDPA) and docked with 10,000 compounds using Ligand Fit (Drug Discovery Studio). Lead molecules with highest binding scores were selected and their efficacy analyzed in in vitro catalytic assays with hTS. Several compounds showed 30% – 50% inhibition of TS activity at 10 μM concentration. These derivatives were more potent than PDPA and inhibited the growth of cells expressing hTS, with IC50s of 100 µM – 200 µM. Data derived from computational and in vitro experiments are being employed in iterative cycles in the design of more potent, allosteric TS inhibitors. 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 1348. doi:10.1158/1538-7445.AM2011-1348
Effects of Golden Hour Thrombolysis
Authors: Martin Ebinger, Alexander Kunz, Matthias Wendt, Michal Rozanski, Benjamin Winter, Carolin Waldschmidt, Joachim Weber, Kersten Villringer, Jochen B. Fiebach, Heinrich J. Audebert
Journal: JAMA Neurology (2014)

<h3>Importance</h3> The effectiveness of intravenous thrombolysis in acute ischemic stroke is time dependent. The effects are likely to be highest if the time from symptom onset to treatment is within 60 minutes, termed the<i>golden hour</i>. <h3>Objective</h3> To determine the achievable rate of golden hour thrombolysis in prehospital care and its effect on outcome. <h3>Design, Setting, and Participants</h3> The prospective controlled Prehospital Acute Neurological Treatment and Optimization of Medical Care in Stroke study was conducted in Berlin, Germany, within an established infrastructure for stroke care. Weeks were randomized according to the availability of a specialized ambulance (stroke emergency mobile unit (STEMO) from May 1, 2011, through January 31, 2013. We included 6182 consecutive adult patients for whom a stroke dispatch (44.1% male; mean [SD] age, 73.9 [15.0] years) or regular care (45.0% male; mean [SD] age, 74.2 [14.9] years) were included. <h3>Interventions</h3> The STEMO was deployed when the dispatchers suspected an acute stroke during emergency calls. If STEMO was not available (during control weeks, when the unit was already in operation, or during maintenance), patients received conventional care. The STEMO is equipped with a computed tomographic scanner plus a point-of-care laboratory and telemedicine connection. The unit is staffed with a neurologist trained in emergency medicine, a paramedic, and a technician. Thrombolysis was started in STEMO if a stroke was confirmed and no contraindication was found. <h3>Main Outcomes and Measures</h3> Rates of golden hour thrombolysis, 7- and 90-day mortality, secondary intracerebral hemorrhage, and discharge home. <h3>Results</h3> Thrombolysis rates in ischemic stroke were 200 of 614 patients (32.6%) when STEMO was deployed and 330 of 1497 patients (22.0%) when conventional care was administered (<i>P</i> &lt; .001). Among all patients who received thrombolysis, the proportion of golden hour thrombolysis was 6-fold higher after STEMO deployment (62 of 200 patients [31.0%] vs 16 of 330 [4.9%];<i>P</i> &lt; .01). Compared with patients with a longer time from symptom onset to treatment, patients who received golden hour thrombolysis had no higher risks for 7- or 90-day mortality (adjusted odds ratios, 0.38 [95% CI, 0.09-1.70];<i>P</i> = .21 and 0.69 [95% CI, 0.32-1.53];<i>P</i> = .36) and were more likely to be discharged home (adjusted odds ratio, 1.93 [95% CI, 1.09-3.41];<i>P</i> = .02). <h3>Conclusions and Relevance</h3> The use of STEMO increases the percentage of patients receiving thrombolysis within the golden hour. Golden hour thrombolysis entails no risk to the patients’ safety and is associated with better short-term outcomes. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01382862
Viscosity of Blood in Myocardial Infarction
Authors: FREDERICK KELLOGG, JOSEPH R. GOODMAN
Journal: Circulation Research (1960)

Following myocardial infarction, the pseudoviscosity of whole blood and the viscosity of plasma increase significantly. The increase in viscosity is correlated with increase in fibrinogen. Both are correlated with the severity of the infarction. The pseudoviseosity of blood adjusted to a hematocrit of 40 shows fair correlation with the viscosity of plasma.
KRAB-independent suppression of neoplastic cell growth by the novel zinc finger transcription factor KS1.
Authors: B Gebelein, M Fernandez-Zapico, M Imoto, R Urrutia
Journal: Journal of Clinical Investigation (1998)

The study of zinc finger proteins has revealed their potential to act as oncogenes or tumor suppressors. Here we report the molecular, biochemical, and functional characterization of KS1 (KRAB/zinc finger suppressor protein 1), a novel, ubiquitously expressed zinc finger gene initially isolated from a rat pancreas library. KS1 contains 10 C2H2 zinc fingers, a KRAB-A/B motif, and an ID sequence that has been shown previously to participate in growth factor-regulated gene expression. Northern blot analysis using pancreatic cell lines demonstrates that KS1 mRNA is inducible by serum and epidermal growth factor, suggesting a role for this gene in cell growth regulation. Biochemical analysis reveals that KS1 is a nuclear protein containing two transcriptional repressor domains, R1 and R2. R1 corresponds to the KRAB-A motif, whereas R2 represents a novel sequence. Transformation assays using NIH3T3 cells demonstrate that KS1 suppresses transformation by the potent oncogenes Ha-ras, Galpha12, and Galpha13. Deletion of the R1/ KRAB-A domain does not modify the transformation suppressive activity of KS1, whereas deletion of R2 abolishes this function. Thus, KS1 is a novel growth factor-inducible zinc finger transcriptional repressor protein with the potential to protect against neoplastic transformation induced by several oncogenes.
REVIEW OF THE BACTERIOLOGY OF ACUTE ARTICULAR RHEUMATISM.
Authors: LEWIS A. CONNER
Journal: JAMA (1907)

The view that regards acute rheumatism as an infectious disease has now gained such general acceptance and has so completely superseded the older "chemical" and "neurotrophic" theories as to its nature that time need not be taken to review the facts which have led to such a general belief. With the growth of this idea of the infectious nature of the disease it was but natural that a search for the infectious agent should begin and but natural also, considering the importance of the disease, that the search should be both eager and persistent. To trace in detail the history of this search for the microbic cause would take us far beyond the scope of this brief paper. A great amount of work on this subject has been done during the past ten years and we can hope only to review briefly the results of this work. As was perhaps
A Syndrome of Methylmalonic Aciduria, Homocystinuria, Megaloblastic Anemia and Neurologic Abnormalities in a Vitamin B<sub>12</sub>-Deficient Breast-Fed Infant of a Strict Vegetarian
Authors: Marilyn C. Higginbottom, Laurence Sweetman, William L. Nyhan
Journal: New England Journal of Medicine (1978)

Original Article from The New England Journal of Medicine — A Syndrome of Methylmalonic Aciduria, Homocystinuria, Megaloblastic Anemia and Neurologic Abnormalities in a Vitamin B12-Deficient Breast-Fed Infant of a Strict Vegetarian
Judge allows a caesarean section to go ahead on a patient without her consent
Authors: C. Dyer
Journal: BMJ (2014)

A High Court judge has given doctors the go ahead to perform a caesarean section on a “highly agitated” 25 year old woman with bipolar disorder without her consent.

The woman, named only as AA, was 38 weeks pregnant with her first child and her membranes had ruptured when she was admitted to Great Western Hospital in Swindon on the evening of 26 January, in a “confused and disoriented” state.

She was said to be experiencing hypermania and puerperal psychosis and was detained under the Mental Health Act the following morning. At 9.30 that night Great Western Hospitals NHS Foundation Trust made an emergency application by telephone to the out of hours judge, Mr …
Effectiveness of Chest Physiotherapy in Infants Hospitalized with Acute Bronchiolitis: A Multicenter, Randomized, Controlled Trial
Authors: Vincent Gajdos, Sandrine Katsahian, Nicole Beydon, Véronique Abadie, Loïc de Pontual, Sophie Larrar, Ralph Epaud, Bertrand Chevallier, Sylvain Bailleux, Alix Mollet-Boudjemline, Jean Bouyer, Sylvie Chevret, Philippe Labrune
Journal: PLoS Medicine (2010)

Vincent Gajdos and colleagues report results of a randomized trial conducted among hospitalized infants with bronchiolitis. They show that a physiotherapy technique (increased exhalation and assisted cough) commonly used in France does not reduce time to recovery in this population.
Variable capacity of L3T4+ T cells to cause lethal graft-versus-host disease across minor histocompatibility barriers in mice.
Authors: R Korngold, J Sprent
Journal: The Journal of Experimental Medicine (1987)

Highly purified populations of L3T4+ and Lyt-2+ T cell subsets were compared for their capacity to cause lethal GVHD in six different H-2-compatible, multiple minor histocompatibility antigen-different murine strain combinations. In four of these combinations (C3H.SW----B6, DBA/2----B10.D2, B10.BR----CBA, and B10.S----SJL), lethal GVHD appeared to be caused almost entirely by Lyt-2+ cells; the injection of L3T4+ cells resulted in low mortality even when these cells were presensitized to the recipient antigens. In the remaining two combinations (B10.D2----DBA/2 and B10.D2----BALB/c), L3T4+ T cells were able to cause a high incidence of GVHD and were more potent than the Lyt-2+ cells. The implications of these findings are discussed.
Gene Therapy With the Caspase Activation and Recruitment Domain Reduces the Ocular Inflammatory Response
Authors: Cristhian J Ildefonso, Henrique Jaime, Manas R Biswal, Shannon E Boye, Qiuhong Li, William W Hauswirth, Alfred S Lewin
Journal: Molecular Therapy (2015)

Inflammation is a key component of chronic and acute diseases of the eye. Our goal is to test anti-inflammatory genes delivered by an adeno-associated virus (AAV) vector as potential treatments for retinal inflammation. We developed a secretable and cell penetrating form of the caspase activation and recruitment domain (CARD) from the apoptosis-associated speck-like protein containing a CARD (ASC) gene that binds caspase-1 and inhibits its activation by the inflammasome. The secretion and cell penetration characteristics of this construct were validated in vitro by measuring its effects on inflammasome signaling in a monocyte cell line and in an retinal pigmented epithelium (RPE) cell line. This vector was then packaged as AAV particles and tested in the endotoxin-induced uveitis mouse model. Gene expression was monitored one month after vector injection by fluorescence fundoscopy. Ocular inflammation was then induced by injecting lipopolysaccharide into the vitreous and was followed by enucleation 24 hours later. Eyes injected with the secretable and cell penetrating CARD AAV vector had both a significantly lower concentration of IL-1β as well as a 64% reduction in infiltrating cells detected in histological sections. These results suggest that anti-inflammatory genes such as the CARD could be used to treat recurring inflammatory diseases like uveitis or chronic subacute inflammations of the eye.
The sight test fee Need for more cautious analysis
Authors: J M Gardner
Journal: BMJ (1994)

and colleagues describe the effect of the introduction of the sight test fee on the number of referrals to Bristol Eye Hospital.'They use the numbers of referrals for 1984-8 to predict the expected numbers of referrals in 1989- 92.This use of their data would have been appropriate if the introduction of the fee on 1 April 1989 had been made without prior warning.The government's proposal for the sight test fee had, however, been made public on 25 November 1987.2This announcement (and subsequent con- firmations) would be expected to have had two effects.Firstly, the high figure for referrals in 1988 may partly simply be due to the increased general publicity about sight tests.Secondly, some people who would have had an eye test after 1 April 1989 may have decided to have one beforehand instead.These "early" sight tests would have increased the figure for referrals in 1988 and reduced that in 1989.The authors consider whether early referrals received in 1988 could account for a reduction in referrals from 1989 onwards.They reject this idea on the grounds that the number of referrals in 1988 was a mere 343 (5 6%) above that expected.Ifthese 343 are regarded as early referrals and are taken from the total for 1988 and added to the total for 1989, however, then the fall in referrals from 1988 to 1989 is not by 15-1% but by only 4-8%.Whether this transfer of numbers of referrals is valid is clearly arguable, but this manoeuvre illustrates that a more cautious analysis might have been appropriate in the study.In particular, it would have been preferable not to have used data for 1988 (the year before introduction of the fee) to predict the numbers of referrals afterwards.If the figure for 1988 is omitted from the analysis the actual numbers of referrals for 1989-92 all fall within the recalculated 95% confidence intervals for the predicted numbers.
Left Atrial Hypertension After Repeated Catheter Ablations for Atrial Fibrillation
Authors: M. Benjamin Shoemaker, Anna R. Hemnes, Ivan M. Robbins, Jonathan J. Langberg, Christopher R. Ellis, Sam G. Aznaurov, Joseph L. Fredi, David A. Slosky, Dan M. Roden, Katherine T. Murray, Robert N. Piana, Lisa A. Mendes, S. Patrick Whalen
Journal: Journal of the American College of Cardiology (2011)
Safety and acceptability of condoms for use by homosexual men as a prophylactic against transmission of HIV during anogenital sexual intercourse.
Authors: L Wigersma, R Oud
Journal: BMJ (1987)

In the Western world the human immunodeficiency virus (HIV), which causes AIDS and AIDS related conditions, is transmitted mainly by anogenital sexual intercourse between men. Since prevention of transmission is at present the only way of controlling the epidemic, prevention programs should be aimed at homosexual men. Information campaigns have resulted in some change in sexual behavior among homosexual men, but additional measures are required. Condoms may prove to be an acceptable and worthwhile means of preventing transmission of the virus during sexual intercourse since the HIV cannot penetrate the intact membrane of latex condoms. 17 male homosexual couples responded to an advertisement in a gay magazine inviting steady couples to participate in a study on the acceptability of condoms. In general, the stiffest condoms seemed to be safer than the others, but they were also the least liked and therefore unacceptable to the participants. Changes are necessary for the successful introduction of condoms as a prophylactic against transmission of the HIV in male homosexuals.
Predicting Survival in Heart Failure Case and Control Subjects by Use of Fully Automated Methods for Deriving Nonlinear and Conventional Indices of Heart Rate Dynamics
Authors: Kalon K. L. Ho, George B. Moody, Chung-Kang Peng, Joseph E. Mietus, Martin G. Larson, Daniel Levy, Ary L. Goldberger
Journal: Circulation (1997)

Background Despite much recent interest in quantification of heart rate variability (HRV), the prognostic value of conventional measures of HRV and of newer indices based on nonlinear dynamics is not universally accepted. Methods and Results We have designed algorithms for analyzing ambulatory ECG recordings and measuring HRV without human intervention, using robust methods for obtaining time-domain measures (mean and SD of heart rate), frequency-domain measures (power in the bands of 0.001 to 0.01 Hz [VLF], 0.01 to 0.15 Hz [LF], and 0.15 to 0.5 Hz [HF] and total spectral power [TP] over all three of these bands), and measures based on nonlinear dynamics (approximate entropy [ApEn], a measure of complexity, and detrended fluctuation analysis [DFA], a measure of long-term correlations). The study population consisted of chronic congestive heart failure (CHF) case patients and sex- and age-matched control subjects in the Framingham Heart Study. After exclusion of technically inadequate studies and those with atrial fibrillation, we used these algorithms to study HRV in 2-hour ambulatory ECG recordings of 69 participants (mean age, 71.7±8.1 years). By use of separate Cox proportional-hazards models, the conventional measures SD ( P &lt;.01), LF ( P &lt;.01), VLF ( P &lt;.05), and TP ( P &lt;.01) and the nonlinear measure DFA ( P &lt;.05) were predictors of survival over a mean follow-up period of 1.9 years; other measures, including ApEn ( P &gt;.3), were not. In multivariable models, DFA was of borderline predictive significance ( P =.06) after adjustment for the diagnosis of CHF and SD. Conclusions These results demonstrate that HRV analysis of ambulatory ECG recordings based on fully automated methods can have prognostic value in a population-based study and that nonlinear HRV indices may contribute prognostic value to complement traditional HRV measures.