tbuckley/cabot-search huggingface dataset:
Fifteen-Year Trends in Risk Severity and Operative Mortality in Elderly Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Joan Ivanov, Richard D. Weisel, Tirone E. David, C. David Naylor
Journal: Circulation (1998)

Background —Trends in risk-severity and operative mortality (OM) were examined in 3330 consecutive patients aged 70 years and older who underwent isolated coronary artery bypass graft surgery (CABG) between 1982 and 1996. Methods and Results —The proportion of elderly patients rose significantly over time ( P &lt;.001). Crude OM among the elderly was 7.2% in 1982 to 1986, fell to 4.4% in 1987 to 1991, but did not improve thereafter. Logistic regression analysis of OM was used to construct relative risk groups (low, medium, or high). The prevalence of high-risk elderly patients rose significantly over time ( P =.001) from 16.2% in 1982 to 1986 to 19.5% in 1987 to 1991 and 26.9% in 1992 to 1996. OM in high-risk patients fell significantly ( P =.044) from 17.2% in 1982 to 1986 to 9.1% in 1987 to 1991 and was 8.9% in 1992 to 1996. Contemporary independent predictors of OM among elderly patients were poor ventricular function (LV grade 2 to 3, odds ratio [OR], 2.6; 95% confidence interval [CI], 1.3 to 5.2; and LV grade 4, OR, 10.7; 95% CI, 4.4 to 26); previous CABG (OR, 3.7; 95% CI, 2.0 to 7.0), female sex (OR, 1.8; 95% CI, 1.1 to 2.8), peripheral vascular disease (OR, 1.8; 95% CI, 1.1 to 2.8), and diabetes (OR, 1.7; 95% CI, 1.1 to 2.7). Previous angioplasty was protective (OR, 0.3; 95% CI, 0.1 to 0.9). Conclusions —OM in elderly patients has declined significantly in recent years despite an increase in the prevalence and severity of their risk factors. A careful weighing of risk, rather than advanced age alone, should determine who is offered surgical revascularization. In this regard, poor ventricular function and repeat CABG continue to have the greatest impact on OM in elderly patients.
Landmark perspective: The Blalock-Taussig operation and subsequent progress in surgical treatment of cardiovascular diseases
Authors: D. G. McNamara
Journal: JAMA (1984)

In 1945, few would have predicted the sustained worldwide interest in, and profound influence on, the surgical treatment of heart disease that would follow the report of three children operated upon for a cyanotic malformation of the heart. The paper was submitted for publication when the patients were only a few months postoperative, probably leading some critics to question whether the report of success was a little premature. The authors acknowledged and defended the promptness of the report as follows: "The results are sufficiently encouraging to warrant an early report."<sup>1</sup> The paper was not a hastily assembled report of a new procedure but included, first, a methodical exposition on the prevailing theories of the mechanism of cyanosis in congenital heart disease, then a step-by-step review of how Dr Taussig developed the concept of surgically increasing the volume of blood to the pulmonary circulation in cyanotic malformations with pulmonary stenosis
Economic and Legal Considerations in Emergency Care
Authors: William J. Curran
Journal: New England Journal of Medicine (1985)

The Arizona Supreme Court recently reviewed a case in order to clarify the law regarding the obligations of physicians and hospitals in rendering emergency care to indigent patients. The opinion could have far-reaching implications, not only for clinical obligations to patients but also for the importance of economic factors in emergency care medicine.In Thompson v. Sun City Community Hospital,1 a minor, age 13, was injured in an accident (not otherwise described) and was rushed by ambulance to a nearby private hospital. The patient suffered, among other injuries, a full or partial transection of the femoral artery high in the . . .
Better reporting of randomised controlled trials: the CONSORT statement
Authors: D. G Altman
Journal: BMJ (1996)

Randomised controlled trials are the best way to compare the effectiveness of different interventions. Only randomised trials allow valid inferences of cause and effect. Only randomised trials have the potential directly to affect patient care—occasionally as single trials but more often as the body of evidence from several trials, whether or not combined formally by meta-analysis. It is thus entirely reasonable to require higher standards for papers reporting randomised trials than those describing other types of study.

Like all studies, randomised trials are open to bias if done badly.1 It is thus essential that randomised trials are done well and reported adequately. Readers should not have to infer what was probably done, they should be told explicitly. Proper methodology should be used and be seen to have been used. Yet reviews of published trials have consistently found major deficiencies in reporting,2 3 4 making the task …
CONSENT IN CLINICAL EXPERIMENTATION: MYTH AND REALITY
Authors: Henry K. Beecher
Journal: JAMA (1966)

The present discussion is directed to experimentation on one individual not for his good but for patients in general. The patient who goes to a physician for relief consents, in the very act of going, to reasonable efforts to treat him, and very often this involves experimentation; our concern at this time presents more difficult problems than this. There is the disturbing and widespread myth that "codes" (all of which emphasize, above all else, consent) will provide some kind of security. While there is value, doubtless, to be gained from their examination as guides to the thinking of others on the subject, the reality is that any rigid adherence to codes can provide a dangerous trap: no two situations are alike; it is impossible to spell out all contingencies in codes. When an accident occurs, in the course of experimentation, it will be easy for the prosecution to show failure
AN UNUSUAL CASE OF ANEMIA.
Authors: GEORGE H. EVANS
Journal: JAMA (1905)

<h3>Patient.</h3> —F. J., aged 36, native of Germany, by occupation a teamster, entered St. Luke's Hospital Sept. 21, 1903. <h3>History.</h3> —Family history unimportant. He drank to excess and smoked moderately. Six years ago he dropped a piece of iron on the first and second toes of the right foot, which accident was followed by "blood poisoning." Three years ago his right eye was destroyed by a shot. About two months ago he had a severe cold and a nosebleed. which lasted two and one-half hours; he lost a great deal of blood. Since then has felt weak and faint. He had nosebleed once since, but not so severely. Bowels were constipated. <h3>Examination.</h3> —Patient was fairly well developed and nourished. Face was pale with dilated capillaries. Right eye was artificial; left reacted normally. Tongue was pale, flabby and tremulous. Lips were pale. Chest was fairly well developed.
Bile alcohol metabolism in man. Conversion of 5beta-cholestane-3alpha, 7alpha,12alpha, 25-tetrol to cholic acid.
Authors: G Salen, S Shefer, T Setoguchi, E H Mosbach
Journal: Journal of Clinical Investigation (1975)

To study the role of C25-HYDROXY BILE ALCOHOLS AS PRECURSORS OF CHOlic acid, [G-3-H]5beta-cholestane-3alpha,7alpha12alpha,25-tetrol was administered intravenously to two subjects with cerebrotendinous xanthomatosis (CTX) and two normal individuals. One day after pulse labeling, radioactivity was present in the cholic acid isolated from the bile and feces of the subjects with CTX and the bile of the normal individuals. In the two normal subjects, the sp act decay curves of [G-3-H]-cholic acid were exponential, and no traces of [G-3-H]-5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol were detected. In contrast, appreciable quantities of labeled 5beta-cholestane-3alpha,-7aopha,12alpha,25-tetrol were present in the bile and feces of the CTX subjects. The sp act vs. time curves of fecal [G-3-H]5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol and [G-3-H]-cholic acid showed a precursor-product relationship. Although these results suggest that 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol may be a precursor of cholic acid in man, the possibility that C26-hydroxy intermediates represent the normal pathway can not be excluded.
LEFT SUPERIOR CERVICAL SYMPATHECTOMY UNDER LOCAL ANESTHESIA IN ANGINA PECTORIS
Authors: Jay Harvey Bacon
Journal: JAMA (1923)

The recent articles of Brown and Coffee, and of Muller., have given added interest to, as well as a summary of, our present knowledge of the control of the sympathetic over the vascular system. The barrenness of the literature on this subject justifies another case report with some remarks on the technic and regional anatomy of this operation. <h3>REPORT OF CASE</h3> G. J., a man, aged 78, a cement worker, born in Germany, who had three healthy adult children over 50, whose father died of cancer at 84, and whose mother died of nephritis at 30, had always been robust. He always had chronic bronchitis, which he believed followed an attack of malaria in childhood. He was a moderate drinker and a very hard worker. About three years ago, while climbing a hill, he was suddenly seized with a heavy feeling in the chest, over the precordium, which quickly disappeared
Familial Incidence of Rheumatoid Arthritis
Authors: J. M. Bremner, W. R. M. Alexander, J. J. R. Duthie
Journal: Annals of the Rheumatic Diseases (1959)

Several studies of the relatives of patients suffering from rheumatoid arthritis have shown a similar small increase in the incidence of the disease as compared with that found among the relatives of healthy controls.In most of these studies (Empire copyright.
Bacterial Delivery of Staphylococcus aureus α-Hemolysin Causes Regression and Necrosis in Murine Tumors
Authors: Adam T St. Jean, Charles A Swofford, Jan T Panteli, Zachary J Brentzel, Neil S Forbes
Journal: Molecular Therapy (2014)

Bacterial therapies, designed to manufacture therapeutic proteins directly within tumors, could eliminate cancers that are resistant to other therapies. To be effective, a payload protein must be secreted, diffuse through tissue, and efficiently kill cancer cells. To date, these properties have not been shown for a single protein. The gene for Staphylococcus aureus α-hemolysin (SAH), a pore-forming protein, was cloned into Escherichia coli. These bacteria were injected into tumor-bearing mice and volume was measured over time. The location of SAH relative to necrosis and bacterial colonies was determined by immunohistochemistry. In culture, SAH was released and killed 93% of cancer cells in 24 hours. Injection of SAH-producing bacteria reduced viable tissue to 9% of the original tumor volume. By inducing cell death, SAH moved the boundary of necrosis toward the tumor edge. SAH diffused 6.8 ± 0.3 µm into tissue, which increased the volume of affected tissue from 48.6 to 3,120 µm3. A mathematical model of molecular transport predicted that SAH efficacy is primarily dependent on colony size and the rate of protein production. As a payload protein, SAH will enable effective bacterial therapy because of its ability to diffuse in tissue, kill cells, and expand tumor necrosis. Bacterial therapies, designed to manufacture therapeutic proteins directly within tumors, could eliminate cancers that are resistant to other therapies. To be effective, a payload protein must be secreted, diffuse through tissue, and efficiently kill cancer cells. To date, these properties have not been shown for a single protein. The gene for Staphylococcus aureus α-hemolysin (SAH), a pore-forming protein, was cloned into Escherichia coli. These bacteria were injected into tumor-bearing mice and volume was measured over time. The location of SAH relative to necrosis and bacterial colonies was determined by immunohistochemistry. In culture, SAH was released and killed 93% of cancer cells in 24 hours. Injection of SAH-producing bacteria reduced viable tissue to 9% of the original tumor volume. By inducing cell death, SAH moved the boundary of necrosis toward the tumor edge. SAH diffused 6.8 ± 0.3 µm into tissue, which increased the volume of affected tissue from 48.6 to 3,120 µm3. A mathematical model of molecular transport predicted that SAH efficacy is primarily dependent on colony size and the rate of protein production. As a payload protein, SAH will enable effective bacterial therapy because of its ability to diffuse in tissue, kill cells, and expand tumor necrosis.
Bayesian Analysis and the GUSTO Trial
Authors: Andrew L. Avins
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The article by Drs Brophy and Joseph<sup>1</sup>is a valuable contribution to the realistic appraisal of clinical trial evidence. Apart from the Bayesian perspective, however, the article highlights a critical problem with the traditional approach to hypothesis testing. The difficulty stems from the tradition of testing a null hypothesis of "no difference" when the more clinically relevant issue is whether there is adequate evidence to reject a hypothesis of "no sufficiently large difference." This is a particularly important distinction when one is comparing two therapies that have different costs, side effects, or other negative consequences. The Global Utilization of Streptokinase and Tissue Plasminogen Activator in Occluded Arteries (GUSTO) trial is a perfect example. A clinician or clinical policymaker may, for example, prefer tissue-type plasminogen activator (t-PA) only if it reduces mortality at least 1% more than streptokinase (SK), given the higher complication rate and greater expense
743 BSEP and MDR3 sequence diversity and haplotype structure in primary sclerosing cholangitis and primary biliary cirrhosis
Authors: C PAULIMAGNUS, K FATTINGER, P MEIER, G KULLAKUBLICK, R KERB, T LANG, U BEUERS
Journal: Hepatology (2003)

Las colestasis genéticas son aquellas debidas a mutaciones inactivadoras que se producen en los genes que codifican las proteínas responsables del transporte de los ácidos biliares y de los fosfolípidos hacia la bilis. Se trata, respectivamente, de los genes ATP8B1 (o FIC1), BSEP (o ABCB11) y MDR3 (o ABCB4). Los cuadros clínicos englobados en esta definición son las colestasis familiares progresivas que afectan a los lactantes, niños e incluso adultos jóvenes, la colestasis recidivante benigna y la litiasis biliar de colesterol de las personas jóvenes (o colelitiasis asociada a una baja concentración de fosfolípidos). La colestasis gravídica se debe a una combinación de variaciones alélicas que se producen en los genes que codifican los transportadores biliares, así como a factores hormonales o ambientales. Las hiperbilirrubinemias genéticas o constitucionales no se acompañan de colestasis. Se deben a anomalías del gen UGTA1, que está encargado de la conjugación de la bilirrubina con el ácido glucurónico (etapa indispensable para la eliminación biliar) y del gen MRP2, responsable del transporte canalicular. Los principales cuadros clínicos están representados por la enfermedad de Gilbert, los síndromes de Crigler-Najjar y el síndrome de Dubin-Johnson.
Do Cardiac Biomarkers NT-proBNP and hsTnT Predict Microvascular Events in Patients With Type 2 Diabetes? Results From the ADVANCE Trial
Authors: Paul Welsh, Mark Woodward, Graham S. Hillis, Qiang Li, Michel Marre, Bryan Williams, Neil Poulter, Louise Ryan, Stephen Harrap, Ansuhka Patel, John Chalmers, Naveed Sattar
Journal: Diabetes Care (2014)

OBJECTIVE We investigated microvascular event risk in people with type 2 diabetes and assessed whether N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) improved prediction. RESEARCH DESIGN AND METHODS We performed a case-cohort study, including 439 incident cases of microvascular events (new or worsening nephropathy or retinopathy) and 2,946 noncase subjects identified from participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. NT-proBNP and hsTnT were measured in stored plasma samples using automated commercial assays. RESULTS After adjustment for age, sex, and randomized treatment, the hazard ratios for microvascular events per 1-SD increase in the log-transformed hsTnT and NT-proBNP were 1.67 (95% CI 1.51–1.85) and 1.63 (1.44–1.84), respectively. After further adjustment for classical and diabetes-related cardiovascular disease risk factors, the hazard ratios attenuated to 1.40 (1.24–1.58) and 1.41 (1.24–1.60), respectively. While the C statistic did not improve on addition of hsTnT or NT-proBNP for the total microvascular end point, a combination of both markers improved the prediction of nephropathy (P = 0.033) but not retinopathy (P = 0.72). The corresponding net reclassification indices in a three–risk category model (&amp;lt;10%, 10–15%, and &amp;gt;15% 5-year risk) for all microvascular events were 7.31% (95% CI 2.24–12.79) for hsTNT addition, 6.23% (1.74–11.5) for NT-proBNP addition, and 7.1% (1.5–12.9) for both markers together. CONCLUSIONS These data suggest that cardiac biomarkers moderately improve microvascular event risk prediction, in particular the risk of nephropathy. Further studies examining the value of this approach for trial design and clinical use are warranted.
Clinical Relevance of Airway 11 β -Hydroxysteroid Dehydrogenase Type II Enzyme in Asthma
Authors: BERNADETTE E. ORSIDA, ZYGMUNT S. KROZOWSKI, E. HAYDN WALTERS
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

11 β -Hydroxysteroid dehydrogenases (11 β -HSD) are responsible for the conversion of bioactive glucocorticoids to and from inactive metabolites. 11 β -HSD2 is generally considered a high-affinity inactivator of natural glucocorticoids, although its activity with synthetic compounds in vivo is unknown. Inhaled corticosteroids (ICS) remain the primary antiinflammatory agents for treating asthma, but little is known about their metabolism in the lung. The aims of this study were to determine whether the 11 β -HSD2 enzyme can be localized to human airway tissue and whether differential expression of this enzyme relates to asthma severity and ICS needs. We studied airway biopsy specimens from 22 asthmatic subjects, in two groups: (1) a group not treated with ICS (n = 7); and (2) a group treated with ICS (range: 200 to 1,500 μ g/d; n = 15). A control population consisted of nine nonasthmatic subjects. Immunostaining was done with an immunopurified antibody to human 11 β -HSD2. Immunoreactivity was generally localized to the endothelium of vessels in the lamina propria and to airway epithelium both in asthmatic patients and nonasthmatic controls. There was a statistically significant inverse relationship between the ICS dose required for effective treatment and the extent of epithelial 11 β -HSD2 staining (r = − 0.44; p = 0.04). This is consistent with 11 β -HSD2 acting as an oxidoreductase that regenerates rather than inactivates ICS. This study suggests that glucocorticoid sensitivity in the lung is not determined by ICS breakdown, but may be related to 11 β -HSD2 sustaining the activation of synthetic glucocorticoids.
DIFFERENTIAL INHIBITORY EFFECTS OF CHOLERA TOXOIDS AND GANGLIOSIDE ON THE ENTEROTOXINS OF <i>VIBRIO CHOLERAE</i> AND <i>ESCHERICHIA COLI </i>
Authors: Nathaniel F. Pierce
Journal: The Journal of Experimental Medicine (1973)

Natural cholera toxoid appears to act as a competitive inhibitor of cholera enterotoxin and is thus a useful tool for studying the interaction of cholera enterotoxin with cell membranes. Cholera enterotoxin binds to gut mucosa more rapidly than does its natural toxoid. Once binding occurs, however, it appears to be prolonged for both materials. Formalinized cholera toxoid has no inhibitory effect upon cholera enterotoxin. Enterotoxic activity, ability to bind to gut mucosa, and antitoxigenicity appear to be independent properties of cholera enterotoxin. Natural cholera toxoid does not inhibit Escherichia coli enterotoxin, indicating that although the two enterotoxins activate the same mucosal secretory mechanism they occupy different binding sites in the mucosa. Ganglioside, which may be the mucosal receptor of cholera enterotoxin, is highly efficient in deactivating cholera enterotoxin. By contrast, ganglioside is relatively inefficient in deactivating heat-labile E. coli enterotoxin and is without effect upon the heat-stable component of E. coli enterotoxin. These findings suggest that ganglioside is not likely to be the mucosal receptor for E. coli enterotoxin. Differences in cellular binding of E. coli and cholera enterotoxins may explain, at least in part, the marked differences in the time of onset and duration of their effects upon gut secretion.
Premature ventricular contractions and reflex sympathetic activation in cats
Authors: F. LOMBARDI, T. G. RUSCONE, A. MALLIANI
Journal: Cardiovascular Research (1989)

In 27 decerebrate cats under various experimental conditions, we studied the effects of programmed premature ventricular contractions on the impulse activity of preganglionic sympathetic fibres isolated from the third left thoracic ramus. Single extrastimuli increased the sympathetic discharge by 319(SEM 43)% [from 10.3(1.7) to 36(3.7) imp.s-1, p less than 0.05]. The neural response was significantly enhanced after bilateral vagotomy by 394(34)% [from 12(2.6) to 53.3(9.8) imp.s-1, p less than 0.05], but abolished when the stimuli were delivered during bilateral carotid artery occlusion. No sympathetic reflex response was observed in cats with chronic sino-aortic denervation. In eight cats, during occlusion of the left anterior descending coronary artery, the control sympathetic response was progressively and reversibly attenuated from 239(28)% to 36(14)%, at 90 s from the beginning of the occlusion. After bilateral vagotomy, this inhibitory interaction was no longer present and the sympathetic neural response to programmed stimulation was maintained throughout the occlusion period. The data indicate that the sympathetic reflex response initiated by baroreceptive deactivation could be attenuated by cardiac vagal afferent activity induced by coronary occlusion.
Hospital doctor's role in the Health of the Nation
Authors: J S Tobias
Journal: BMJ (1995)

time is too short in the modem NHS to give such an explanation, others will say that they never explain and will not do so now, and others will feel natural inhibition at admitting that they have been negligent.It is therefore vital that a professional duty of candid disclosure is imposed on doctors so that patients are told when doctors have been negligent in their care and treatment and are given a clear, full, and honest explanation.The knock on effects should be that patients have much greater confidence in doctors and hospitals, that they trust their doctors more, and that many potential actions for medical negligence will be defused before the patient even considers bringing a claim.If the patient, even in the light of a full explanation, nevertheless decides to bring a claim against the doctor the case is likely to be cheaper and less painful for both the doctor and the patient.Furthermore, full explanation may prevent those claims against doctors that are not justified and that are so time consuming for busy practitioners that they cannot care for the other patients in need of their skills.There seem to us to be advantages on every side.
Pulmonary hypertension and fenfluramine
Authors: J G Douglas, J F Munro, A H Kitchin, A L Muir, A T Proudfoot
Journal: BMJ (1981)

Pulmonary hypertension developed in two women who had been taking fenfluramine for over eight months for weight reduction. On withdrawing the drug symptoms and electrocardiographic evidence of pulmonary hypertension disappeared in both cases. In one patient, however, the evidence recurred after rechallenge with fenfluramine. These findings are strong evidence that fenfluramine may cause pulmonary hypertension. Hence any patient taking the drug should report immediately any deterioration in exercise tolerance.