tbuckley/cabot-search huggingface dataset:
Relation of Increased Arterial Blood Pressure to Mortality and Stroke in the Context of Contemporary Thrombolytic Therapy for Acute Myocardial Infarction
Authors: Philip E. Aylward, Robert G. Wilcox, John H. Horgan, Harvey D. White, Christopher B. Granger, Robert M. Califf, Eric J. Topol
Journal: Annals of Internal Medicine (1996)

Background: Despite concern that hypertension increases the risk for intracranial hemorrhage during thrombolysis for acute myocardial infarction, the exact nature of the risk remains unclear. Objective: To assess the effects of previous hypertension and blood pressure at study entry on the outcomes of patients who had acute myocardial infarction and received thrombolysis. Design: Randomized trial. Setting: 1081 hospitals in 15 countries. Patients: 41 021 patients who had myocardial infarction accompanied by ST-segment elevation and who presented to hospitals within 6 hours of symptom onset. Intervention: One of four thrombolytic regimens. Main Outcome Measures: Mortality, stroke subtypes, and death plus disabling stroke in patients with previous hypertension and as functions of blood pressure at entry. Logistic regression analysis of relations among blood pressure at entry, baseline characteristics, and treatment effects. Results: The incidence of total stroke and intracranial hemorrhage increased as systolic blood pressure at entry increased and was particularly high for systolic pressures of about 175 mm Hg or more (incidence of total stroke, 3.4% compared with 1.17% for pressures between 100 and 124 mm Hg). Patients who had systolic blood pressure of 175 mm Hg or more at entry and who received accelerated alteplase therapy had a lower rate of death within 30 days (4.3% compared with 7.8%; P = 0.044) and a lower rate of death plus disabling stroke (4.9% compared with 8.9%; P = 0.031) than patients treated with streptokinase, despite having higher rates of total and hemorrhagic stroke (incidence of hemorrhagic stroke, 2.3% compared with 1.5%). Assumptions based on previous trials and rates of stroke from the GUSTO-I (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries) trial suggest that in hypertensive patients with low risk for death from cardiac causes (no previous infarction, Killip class I), the risk-to-benefit ratio with thrombolysis is about unity, with about 13 lives saved per 1000 persons treated at the risk of about 13 intracranial hemorrhages. Conclusions: Patients with myocardial infarction and very elevated blood pressure who have thrombolysis and patients with myocardial infarction who do not have elevated blood pressure have a similar risk for death, but the risk for stroke is higher in the former group. Future studies should assess 1) the risk-to-benefit ratio of thrombolysis in these patients, especially those at low risk for death from cardiac causes, and 2) whether decreasing elevated blood pressure before thrombolysis reduces the incidence of stroke without increasing mortality rates.
Investigation of Loss and Gain of Introns in the Compact Genomes of Pufferfishes (Fugu and Tetraodon)
Authors: Y.-H. Loh, S. Brenner, B. Venkatesh
Journal: Molecular Biology and Evolution (2007)

We have investigated intron evolution in the compact genomes of 2 closely related species of pufferfishes, Fugu rubripes and Tetraodon nigroviridis, that diverged about 32 million years ago (MYA). Analysis of 148,028 aligned intron positions in 13,547 gene pairs using human as an outgroup identified 57 and 24 intron losses in Tetraodon and fugu lineages, respectively, and no gain in either lineage. For comparison, we analyzed 144,545 intron positions in 12,866 orthologous pairs of genes in human and mouse that diverged about 61 MYA using dog as an outgroup and identified 51 intron losses in mouse and 3 losses in human and no gain. The rate of intron loss in Tetraodon is higher than that in fugu, mouse, and human but lower than the previous estimates for other eukaryotes. The introns lost in pufferfishes and mammals are significantly shorter than the mean size of introns in the genome. One intron deleted in fugu and another in Tetraodon have left behind 6 and 3 nucleotides, respectively, suggesting that they were lost due to genomic deletions. Such losses of introns are likely to be the result of a higher rate of DNA deletions experienced by the genomes of pufferfishes compared with mammals. The shorter generation time of Tetraodon compared with fugu, and the rich diversity and higher activity of transposable elements in pufferfishes compared with mammals, may be responsible for the higher rate of intron loss in Tetraodon. Our findings indicate that overall very little intron turnover has occurred in pufferfishes and mammals during recent evolution and that intron gain is an extremely rare event in vertebrate evolution.
Echocardiographic recognition of the mitral valve-posterior aortic wall relationship.
Authors: B L Strunk, S B Guss, R E Hicks, M N Kotler
Journal: Circulation (1975)

Aortic-mitral valve discontinuity has previously been described in double outlet right ventricle, endocardial cushion defect, single ventricle, tetralogy of Fallot, and prolapse of the mitral valve. We are reporting two additional examples of aortic-mitral valve discontinuity including 15 cases of gross left ventricular dilation and a case of acute pneumococcal bacterial endocarditis with a large subannular erosion. While nonspecific, aortic-mitral valve discontinuity is a clinically important sign that should be sought with slow-M-mode scanning and strip chart recording.
No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis
Authors: Amke Caliebe, Rabea Kleindorp, Hélène Blanché, Lene Christiansen, Annibale Alessandro Puca, Irene Maeve Rea, Eline Slagboom, Friederike Flachsbart, Kaare Christensen, Gerald Rimbach, Stefan Schreiber, Almut Nebel
Journal: Ageing Research Reviews (2010)
Feeding in Typhoid Fever.
Authors: Jacob L. Williams
Journal: JAMA (1901)

prise at having the treatment unhesitatingly condemned by a man some hundreds of miles away, who is and was as ignorant of what was actually indicated and done as he appears to be of the courtesies due between professional gentlemen.Snap diagnoses and absent treatment have heretofore been confined to magnetic healers and "Christian Scientists," and this brief experience leads me to hope that such methods will never be adopted by reputable professional men.Very re- spectfully,
Increased Airway Pressure and Simulated Branch Pulmonary Artery Stenosis Increase Pulmonary Regurgitation After Repair of Tetralogy of Fallot
Authors: Rajiv R. Chaturvedi, Philip J. Kilner, Paul A. White, Andrew Bishop, Richard Szwarc, Andrew N. Redington
Journal: Circulation (1997)

Background Pulmonary regurgitation (PR) is an important determinant of outcome after repair of tetralogy of Fallot. Baseline PR was measured by magnetic resonance (MR) phase velocity mapping and from real-time right ventricular pressure-volume loops with a conductance catheter. Subsequently, the impact of two loading maneuvers (increased airway pressure, simulated branch pulmonary artery stenosis) on PR was assessed by the conductance catheter method. Methods and Results Thirteen patients, 3 to 35 years after tetralogy of Fallot repair or pulmonary valvotomy, had PR measured by MR phase velocity mapping while breathing spontaneously. During catheterization under general anesthesia, PR was estimated from right ventricular pressure-volume loops generated by conductance and microtip pressure catheters. The effect of increased airway pressure (continuous positive airway pressure, 20 cm H 2 O; n=12) and simulated branch pulmonary artery stenosis (transient balloon occlusion of a branch pulmonary artery, n=7) was measured. Basal PR fraction derived by MR and from right ventricular pressure-volume loops had a correlation coefficient of .76 and mean of differences of 2.0±18.2% (95% limits of agreement). Increased airway pressure increased PR (16.3±11.4% to 25.7±17.3%, P &lt;.01). Simulated branch pulmonary artery stenosis increased right ventricular end-systolic pressure (69.1±21.4 to 78.7±23.1 mm Hg, P &lt;.05) and PR (27.5±11.3% to 36.9±12.8%, P &lt;.05). Conclusions There was reasonable agreement between MR phase velocity–derived PR fraction and that obtained from right ventricular pressure-volume loops generated by use of conductance and pressure-microtip catheters. Exacerbation of PR by increased airway pressure and branch pulmonary stenosis may be relevant to the acute postoperative and long-term management, respectively, of patients after repair of tetralogy of Fallot.
National early warning score (NEWS) is not suitable for all patients
Authors: G. M. Teasdale
Journal: BMJ (2012)

McGinlay and Pearse worry about the use of the national early warning score (NEWS) in people recovering from brain injury,1 2 but its insensitivity in people developing acute brain insults is also worrying.

In the assessment of brain dysfunction, NEWS depends solely on the “alert, verbal, pain, unresponsive (AVPU)” system. Although useful in initial triage, such simplicity is inadequate in monitoring hospital patients at risk of neurological deterioration. Crucially, AVPU findings are compressed to only …
Dantrolene rescues aberrant N-terminus intersubunit interactions in mutant pro-arrhythmic cardiac ryanodine receptors
Authors: Monika Seidel, N. Lowri Thomas, Alan J. Williams, F. Anthony Lai, Spyros Zissimopoulos
Journal: Cardiovascular Research (2014)

AimsThe ryanodine receptor (RyR2) is an intracellular Ca2+ release channel essential for cardiac excitation–contraction coupling. Abnormal RyR2 channel function results in the generation of arrhythmias and sudden cardiac death. The present study was undertaken to investigate the mechanistic basis of RyR2 dysfunction in inherited arrhythmogenic cardiac disease.
Exam 1: Acute Acalculous Cholecystitis: A Review
Authors: Charles O. Elson
Journal: Clinical Gastroenterology and Hepatology (2009)

Acute Acalculous Cholecystitis: A ReviewClinical Gastroenterology and HepatologyVol. 8Issue 1PreviewAlthough recognized for more than 150 years, acute acalculous cholecystitis (AAC) remains an elusive diagnosis. This is likely because of the complex clinical setting in which this entity develops, the lack of large prospective controlled trials that evaluate various diagnostic modalities, and thus dependence on a small data base for clinical decision making. AAC most often occurs in critically ill patients, especially related to trauma, surgery, shock, burns, sepsis, total parenteral nutrition, and/or prolonged fasting. Full-Text PDF
The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs.
Authors: K A Reimer, J E Lowe, M M Rasmussen, R B Jennings
Journal: Circulation (1977)

Irreversible ischemic myocardial cell injury developes in an increasing number of cells as the duration of coronary occlusion is prolonged. The present study quantitates myocardial necrosis produced by 40 minutes, 3 hours, or 6 hours of temporary circumflex coronary occlusion (CO) followed by 2 to 4 days of reperfusion, or by 24 or 96 hours of permanent circumflex ligation in pentobarbital anesthetized open chest dogs. After 40 minutes of ischemia, myocyte necrosis was subendocardial but with increasing duration of coronary occlusion, irreversible injury progressed as a wavefront toward the subepicardium. Transmural necrosis was 38 +/- 4% after 40 min, 57 +/- 7% after 3 hours, 71 +/- 7% after 6 hours and 85 +/- 2% after 24 hours of ischemic injury. These results document the presence of a subepicardial zone of ischemic but viable myocardium which is available for pharmacologic or surgical salvage for at least three and perhaps six hours following circumflex occlusion in the dog.
Effect of Cell Wall Skeleton and Monophosphoryl Lipid A Adjuvant on the Immunogenicity of a Murine B16 Melanoma Vaccine
Authors: Dean Johnston, Jean-claude Bystryn
Journal: JNCI Journal of the National Cancer Institute (1991)

We examined the effect of a new adjuvant consisting of purified mycobac-terial cell wall skeleton (CWS) and monophosphoryl lipid A (MPL) on the immunogenicity of a murine melanoma vaccine. C57BL/6 mice were immunized to partially purified B16 melanoma vaccine given alone or together with different dose levels of adjuvant, or with saline or adjuvant alone. Humoral response, delayed-type hypersensitivity (DTH), in vitro cytotoxicity, and tumor-protective immunity to melanoma were measured following three biweekly immunizations. The adjuvant potentiated the antibody response to some, but not all, melanoma antigens in a dose-dependent fashion. The adjuvant also potentiated cellular immunity as measured by in vitro cytotoxicity assays. No potentiation of tumor-protective immunity was detected. In comparision to Freund's complete adjuvant, cell wall skeleton plus monophosphoryl lipid A (CWS: MPL) induced fewer cutaneous toxic effects and stronger antibody and DTH responses but resulted in no greater in vitro cytotoxicity or tumor-protective immunity. Thus, the adjuvant had a selective and dose-dependent effect on humoral responses to vaccine immunization but did not potentiate a tumor-protective immunity to B16 melanoma. [J Natl Cancer Inst 83:1240–1245, 1991]
Working miracles for the NHS
Authors: N. Hawkes
Journal: BMJ (2015)

How realistic are the predictions of the Five Year Forward View ?



Since he published his Five Year Forward View in October, Simon Stevens has been walking on water. The chief executive of NHS England is (temporarily) able to do no wrong. Just as Melanesian islanders attribute magical powers to charismatic outsiders, Stevens has acquired a cargo cult of his own, deliciously lampooned in a series of tweets by the journalist Andy Cowper under the hashtag #SimonStevensfacts.

Here’s a sample. “Hot? Bothered? Chant NHS England three times and Simon Stevens will appear with a chilled bottle of mineral water.” Impressive, but not quite as awe inspiring as another fact unearthed by Cowper. “Simon Stevens mined the Large Hadron Collider’s 27-km particle accelerator tunnels in a lunch break, using a plastic spoon.”

Joking aside, it does seem that Stevens can currently get away with things that would bring derision on the heads of ordinary folk. For example, he has redefined the intervention process designed to rescue failing NHS services as a “success regime” rather than a “failure regime” to avoid demotivation and stigma. If his predecessor, David “Ironman” Nicholson, had tried something like this, laughter would have rolled irresistibly across the land. From Stevens it’s pure gold.

Still, when every utterance is given super-credibility there is …
Group C β-Hemolytic Streptococci in College Students With Pharyngitis-Reply
Authors: Gregory F. Hayden
Journal: JAMA (1991)

<h3>In Reply.—</h3> Dr Waters and Ms Cook raise some interesting points. When we began our study, we lacked a priori evi dence that respiratory illnesses, if any, caused by non-group A streptococci would be clinically similar to those caused by the more familiar group A organisms. We cast a broad net, therefore, and included all patients with the chief complaint of sore throat. Based on the clinical features of our patients with group C isolates, it now appears that many patients with sore throat associated with group C streptococci have similar clinical features to those with group A isolates. To determine whether our original control group reliably reflects the actual carriage rate of group C streptococci, we have subsequently studied two additional populations of healthy controls. We have found a virtually identical isolation rate (12%) of group C streptococci on throat culture in a total of 250 healthy students at
692 NOS-3 REGULATION BY OXIDATIVE STRESS IN A CELLULAR MODEL OF CHOLESTATIC DAMAGE
Authors: S. González-Rubio, C.I. Linares, P. Aguilar, A. Fernández-Álvarez, M. Casado, J. Briceño, L. Casáis, J.L. Montero, J. Muntané, M. de la Mata, G. Ferrín
Journal: Journal of Hepatology (2013)
The other side of medicine
Authors: Edward C A Barrett
Journal: BMJ (2004)

Going to work in the week before Christmas, I was reminded of an event in my school days. As 11 year olds, we were asked to write a piece of prose about Christmas. Understandably, we all set to work writing about food, presents, and festivities. Well, not quite all: one of my classmates surprised us all, and left an impression on some of us, by writing an account titled “The other side of Christmas,” in which he described the Christmas …
The General Medical Council responds to the special report in The BMJ on regulating doctors' financial and commercial interests
Authors: N. Dickson
Journal: BMJ (2015)

The General Medical Council takes the issue of conflicts of interests very seriously.1 We have unambiguous guidance which sets out our expectations—doctors must not allow any potential conflict to influence their practice and must always be open and honest with patients.2 3

If a doctor fails to follow our guidance we can and do take action. Since 2006, 34 doctors have …
Cowpox infection causing a generalized eruption in a patient with atopic dermatitis
Authors: S. BLACKFORD, D.L. ROBERTS, P.D. THOMAS
Journal: British Journal of Dermatology (1993)

Journal Article Cowpox infection causing a generalized eruption in a patient with atopic dermatitis Get access S. BLACKFORD, S. BLACKFORD Department of Dermatology, Singleton Hospital, Sketty, Swansea, West Glamorgan SA2 8QA, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.L. ROBERTS, D.L. ROBERTS Department of Dermatology, Singleton Hospital, Sketty, Swansea, West Glamorgan SA2 8QA, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.D. THOMAS P.D. THOMAS Department of Microbiology, Singleton Hospital, Sketty, Swansea, West Glamorgan SA2 8QA, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 129, Issue 5, 1 November 1993, Pages 628–629, https://doi.org/10.1111/j.1365-2133.1993.tb00500.x Published: 01 November 1993 Article history Accepted: 17 May 1993 Published: 01 November 1993
Methylenetetrahydrofolate reductase polymorphism associated with moderate hyperhomocysteinaemia in a patient with livedo vasculopathy: treatment with vitamin supplementation and low molecular weight heparin
Authors: J. Rampf, C. Sunderkötter, G. Hirschfeld, K. Scharffetter-Kochanek, J.M. Weiss
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Sir, Livedo vasculopathy, a distinct form of thrombogenic vasculopathy, is characterized by recurrent painful ulcers of the lower extremity with persistent livedo racemosa.1 High levels of homocysteine are an independent risk factor for arterial occlusive diseases and deep vein thrombosis.2 One study demonstrated a possible association between plasma homocysteine levels and livedo vasculopathy.3, 4 The key enzyme controlling remethylation of homocysteine is 5,10‐methylenetetrahydrofolate reductase (MTHFR). An alanine/valine gene polymorphism caused through a C to T substitution at nucleotide 677 is responsible for a reduced MTHFR activity and increased thermolability of this enzyme in homozygous individuals, resulting in increased plasma homocysteine concentrations, particularly under conditions of low dietary folate intake. We report livedo vasculopathy in a patient with moderate hyperhomocysteinaemia due to homozygous MTHFR gene mutation. A 42‐year‐old woman presented with livedo racemosa and several small bizarrely shaped ulcers and atrophie blanche on the dorsal aspect of both feet and ankles (Fig. 1). Dorsal arteries of both feet were palpable. Colour‐coded duplex sonography and Doppler sonography revealed no signs of venous insufficiency. Ulcers had previously occurred during the summer months and healed with ivory‐coloured scars. The patient denied other medical problems, intake of medications, vitamin supplements, alcohol or drugs, but smoked five cigarettes per day.
Excess risk of maternal mortality in adolescent mothers – Authors' reply
Authors: Andrea Nove, Zoë Matthews, Sarah Neal, Alma Virginia Camacho
Journal: The Lancet Global Health (2014)

We strongly agree with Ann Blanc, who clearly highlights the dangers of so-called accepted wisdom based on limited or flawed evidence, and the need to question and probe the provenance of data used to direct resources and plan policies. This is indeed an important lesson for the maternal health community as we move forward with setting priorities for national and global maternal health agendas. We would also like to emphasise that we do not see our findings as negating the need to focus on reducing adolescent births in some contexts. Increased risk of mortality is only one of the potential negative outcomes that can result from early motherhood, and a holistic approach that assesses evidence of potential adverse effects on education, opportunities, and general wellbeing, as well as health (for mother and baby) should be used to guide policy in this area. We were also unable in our study to estimate whether younger adolescents (eg, aged 12–15 years)1Neal S Matthews Z Frost M Fogstad H Camacho AV Laski L Childbearing in adolescents aged 12–15 in developing countries: a neglected issue. New estimates from demographic and household surveys in 42 countries.Acta Obstet Gynecol Scand. 2012; 91: 1114-1118Crossref PubMed Scopus (132) Google Scholar experienced higher mortality than their older adolescent counterparts, and this is an area we will be researching in future to further develop our understanding of risks to young mothers. We declare that we have no competing interests. Excess risk of maternal mortality in adolescent mothersAndrea Nove and colleagues (March, 2014)1 report compelling and much-needed evidence on the global age pattern of maternal mortality. Their analysis concludes that the excess mortality risk faced by mothers aged 15–19 years might be “less than previously believed”. As the authors point out, this evidence is consistent with our own similar analysis of data from a smaller number of countries.2 Full-Text PDF Open AccessMaternal mortality in adolescents compared with women of other ages: evidence from 144 countriesOur findings suggest that the excess mortality risk to adolescent mothers might be less than previously believed, and in most countries the adolescent maternal mortality ratio is low compared with women older than 30 years. However, these findings should not divert focus away from efforts to reduce adolescent pregnancy, which are central to the promotion of women's educational, social, and economic development. Full-Text PDF Open Access
Trimethoprim and Sulfamethoxazole in Pregnancy
Authors: A. Gonzalez Ochoa
Journal: JAMA (1971)

<h3>To the Editor.—</h3> New drugs must be considered as contraindicated during pregnancy, especially at the time of organogenesis. The trimethoprim-sulfamethoxazole combinations (Bactrim, Septrin) are apparently not teratogenic in animals when given in therapeutic doses. However fetal malformation, such as experimental folate deficiency, can be produced by higher doses in rats. The combination of trimethoprim and sulfamethoxazole has been given for the treatment of bacteriuria to a series of 120 pregnant women (ten of these in the first trimester) apparently without evidence of a teratogenic effect.<sup>1</sup>An additional patient has been successfully treated with trimethoprim and sulfamethoxazole without interruption for 14 months, starting six months before pregnancy. A 30-year-old woman, born in Michoacan, Mexico, had an actinomycetic mycetoma of the left foot of 11 years' duration with involvement of the calcaneus.<i>Nocardia brasiliensis</i>was obtained on culture. Since 1965 she had been treated with 300 mg of dapsone per day,