tbuckley/cabot-search huggingface dataset:
KEGG spider: interpretation of genomics data in the context of the global gene metabolic network
Authors: Alexey V Antonov, Sabine Dietmann, Hans W Mewes
Journal: Genome biology (2008)

Abstract KEGG spider is a web-based tool for interpretation of experimentally derived gene lists in order to gain understanding of metabolism variations at a genomic level. KEGG spider implements a 'pathway-free' framework that overcomes a major bottleneck of enrichment analyses: it provides global models uniting genes from different metabolic pathways. Analyzing a number of experimentally derived gene lists, we demonstrate that KEGG spider provides deeper insights into metabolism variations in comparison to existing methods.
Tranexamic acid as an aid to reducing blood transfusion requirements in gastric and duodenal bleeding.
Authors: C C von Holstein, S B Eriksson, R Kallen
Journal: BMJ (1987)

A prospective randomised double blind study examined the effect of the antifibrinolytic drug tranexamic acid compared with placebo in 154 patients bleeding from verified benign lesions in the stomach or duodenum or both. Three out of 72 patients receiving tranexamic acid underwent emergency surgery compared with 15 out of 82 given placebo (p = 0.010). Nineteen patients receiving placebo rebled during their admission as compared with 10 in the active treatment group (p = 0.097). Blood transfusion requirements were significantly reduced by tranexamic acid (p = 0.018). Side effects occurred in six patients, of which an uncomplicated deep venous thrombosis was the most severe. Tranexamic acid reduces the blood transfusion requirement and need for emergency surgery in patients bleeding from a benign gastric or duodenal lesion.
Zen and the Art of Physician Autonomy Maintenance
Authors: James L. Reinertsen
Journal: Annals of Internal Medicine (2003)

The miracles of scientific medicine propelled physicians to an unparalleled level of clinical autonomy during the 20th century. During the past 20 years, physician autonomy has been declining, in part because the public has become aware that physicians are not consistently applying all of the science they know. One of medicine's most cherished professional values, individual clinical autonomy, is an important cause of the sometimes suboptimal performance in the timely and consistent application of clinical science; thus, it contributes to the decline in overall professional autonomy. This paper calls for physicians to practice the science of medicine as a profession so that society will allow physicians to continue practicing the art of medicine as individual professionals. In a Zen-like paradox, physicians must give up autonomy in order to regain it.
TRAUMATIC SHOCK. VI. THE EFFECT OF HEMORRHAGIC SHOCK ON THE CONCENTRATION OF RENIN AND HYPERTENSINOGEN IN THE PLASMA IN UNANESTHETIZED DOGS 1
Authors: Lewis Dexter, Howard A. Frank, Florence W. Haynes, Mark D. Altschule
Journal: Journal of Clinical Investigation (1943)

Recent investigations have suggested that the renal enzyme, renin, plays a homeostatic role in the maintenance of normal blood pressure, since its concentration in the blood increases in a va- riety of hypotensive states, including shock due to hemorrhage (1 to 5).It seemed desirable to re-study this phenomenon in unanesthetized animals in order to avoid the complicating factor of anesthesia and to make additional studies on its mechanism and its action.Accordingly, observations have also been made in nephrectomized dogs, and in animals responding favorably or unfavorably to transfusion after hemorrhage.The blood of all animals studied has been assayed for hypertensinogen, since, on theoretical grounds, an in- crease in the concentration of renin in the blood might result after a time in a decrease in the con- centration of hypertensinogen.
Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease
Authors: Kerry L. Donnelly, Coleman I. Smith, Sarah J. Schwarzenberg, Jose Jessurun, Mark D. Boldt, Elizabeth J. Parks
Journal: Journal of Clinical Investigation (2005)

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess liver triacylglycerol (TAG), inflammation, and liver damage. The goal of the present study was to directly quantify the biological sources of hepatic and plasma lipoprotein TAG in NAFLD. Patients (5 male and 4 female; 44 ± 10 years of age) scheduled for a medically indicated liver biopsy were infused with and orally fed stable isotopes for 4 days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipoprotein TAG. Hepatic and lipoprotein TAG fatty acids were analyzed by gas chromatography/mass spectrometry. NAFLD patients were obese, with fasting hypertriglyceridemia and hyperinsulinemia. Of the TAG accounted for in liver, 59.0% ± 9.9% of TAG arose from NEFAs; 26.1% ± 6.7%, from DNL; and 14.9% ± 7.0%, from the diet. The pattern of labeling in VLDL was similar to that in liver, and throughout the 4 days of labeling, the liver demonstrated reciprocal use of adipose and dietary fatty acids. DNL was elevated in the fasting state and demonstrated no diurnal variation. These quantitative metabolic data document that both elevated peripheral fatty acids and DNL contribute to the accumulation of hepatic and lipoprotein fat in NAFLD.
ON THE NATURE AND CAUSES OF THE PHYSIOLOGICAL PHENOMENA
Authors: S. T. Speer
Journal: BMJ (1853)

In the second instance, the vy worst houssurgoon in- flicted on a public hospital, was the highest prize-man in his college, and was elected on the strength of his prizes.jis abilities were excellent; but he had devoted with diligence all his powers to the acquisition of words from books, and broke down in an appointment which demanded -a knowledge of thinga.The system has been to blame, not the student; and we -thank the University of London for having begun pro- -minently to adopt a more scientific mode of examination, and for thus giving us the promise of a more capable set of junior practitioners.
George Harry Hall
Authors: W. Hamilton, A. Round, T. Feest
Journal: BMJ (2011)

After training at University College Hospital, London, George Harry Hall (“Harry”) worked in London and Bristol, plus a spell of national service in the Royal Air Force. A year in Philadelphia studying the pathophysiology of finger clubbing was thoroughly enjoyed, though showed him that academia would not suit his temperament in the long term.

Appointed to a rheumatology post in the Royal Devon and Exeter Hospital, he began to display the lifelong characteristics that made him so well respected: an unwavering commitment to patient care, an intellectually rigorous approach to treatment, and a demand that the NHS offer the best possible, up to …
Disruption of ECE-1 and ECE-2 reveals a role for endothelin-converting enzyme-2 in murine cardiac development
Authors: Hiromi Yanagisawa, Robert E. Hammer, James A. Richardson, Noriaki Emoto, S. Clay Williams, Shin-ichi Takeda, David E. Clouthier, Masashi Yanagisawa
Journal: Journal of Clinical Investigation (2000)

Endothelin-converting enzyme-1 and -2 (ECE-1 and -2) are membrane-bound metalloproteases that can cleave biologically the inactive endothelin-1 (ET-1) precursor to form active ET-1 in vitro. We previously reported developmental defects in specific subsets of neural crest–derived tissues, including branchial arch–derived craniofacial structures, aortic arch arteries, and the cardiac outflow tract in ECE-1 knockout mice. To examine the role of ECE-2 in cardiovascular development, we have now generated a null mutation in ECE-2 by homologous recombination. ECE-2 null mice develop normally, are healthy into adulthood, are fertile in both sexes, and live a normal life span. However, when they are bred into an ECE-1–null background, defects in cardiac outflow structures become more severe than those in ECE-1 single knockout embryos. In addition, ECE-1–/–; ECE-2–/– double null embryos exhibited abnormal atrioventricular valve formation, a phenotype never seen in ECE-1 single knockout embryos. In the developing mouse heart, ECE-2 mRNA is expressed in the endocardial cushion mesenchyme from embyronic day (E) 12.5, in contrast to the endocardial expression of ECE-1. Levels of mature ET-1 and ET-2 in whole ECE-1–/–; ECE-2–/– embryos at E12.5 do not differ appreciably from those of ECE-1–/– embryos. The significant residual ET-1/ET-2 in the ECE-1–/–; ECE-2–/– embryos indicates that proteases distinct from ECE-1 and ECE-2 can carry out ET-1 activation in vivo.
Accuracy of perception of severity of asthma: patients treated in general practice.
Authors: A H Kendrick, C M Higgs, M J Whitfield, G Laszlo
Journal: BMJ (1993)

OBJECTIVE--To determine the frequency of poor perception of severity of asthma in general practice. DESIGN--Asthmatic patients recorded their perceived severity of asthma, with a visual analogue score, and a coded measurement of their peak expiratory flow up to four times daily for 14 consecutive days. SETTINGS--11 general practices in and around Bristol. SUBJECTS--255 asthmatic patients (139 men and 116 women) aged 17-76 who were recruited by random selection from the general practices9 disease registers or when they requested prescriptions for inhaled bronchodilators. MAIN OUTCOME MEASURES--Correlation between visual analogue scores and peak expiratory flow (as a percentage of predicted peak flow). RESULTS--152 (60%) of the patients showed no significant correlation between visual analogue asthma scores and simultaneous peak flow measurements (p &gt; 0.05) and were termed poor discriminators. The distribution of good and poor discriminators within each general practice was similar (chi 2 = 6.11, df = 10). The two groups were not characterised by differences in the maximum, minimum, or standard deviation of peak expiratory flow or visual analogue score; in age; or in the proportion of men and women in each group. CONCLUSIONS--In general practice a high proportion of asthmatic patients do not reliably detect changes in their lung function. This reinforces the need for careful objective assessment of lung function in the management of asthma.
Abstract P111: Applying the Principles of Functional Stimulation to Electrical CPR
Authors: Byron L Gilman, James Brewer, Mark W Kroll, Giuseppe Ristagno, Yongqin Li, Hao Wang, Shijie Sun, Max Harry Weil, Wanchun Tang
Journal: Circulation (2008)

Background: We have previously reported on a specialized electrical stimulus that produces coronary and carotid blood flow during VF. The values selected for the Current (C), Pulse Width (PW), Pulse Period (PP), Train Width (TW) and Train Rate (TR) are critical to obtaining effective blood flow. An initial experiment in which these parameters were systematically studied in order to identify the optimal parameters has been previously reported. In this study we utilized some of the principles established in the field of NeuroMuscular Electrical Stimulation (NMES) of the extremities to further optimize ECPR. A primary principle of interest is that the force produced is proportional to charge delivered (Coulombs or amp-seconds.) Consequently, higher C, longer PW, shorter PP and longer TW would be predicted to produce greater force. Hypothsis: We hypothesized that for ECPR as in NMES that: CPP over time would be proportional to the total charge delivered per constriction. Methods: We applied 118 episodes of ECPR in 7 porcine subjects as previously described. VF was electrically induced and untreated for 10 seconds. ECPR was then applied for 60 seconds or until CPP dropped below 15 mm Hg. The specific ECPR intervention applied was determined according to a factorial design of experiment in which two levels each of C, PW, PP and TW were evaluated. The CPP was recorded at 10-second intervals during ECPR until it was terminated. Results: PP and PW showed significant differences in their ability to maintain CPP &gt; 15 mm Hg (T15) for prolonged periods of time (PP=25 ms: 49±15 s to T15 vs PP=50 ms: 41±17 s to T15, p=0.004) (PW=0.2 ms: 42±17 s to T15 vs PW=0.8 ms: 48±16 s to T15, p=0.05). Regression analysis further showed that an increase in PW and a decrease in PP worked independently and without interaction to increase T15 for CPP. These two parameters relate directly to total charge delivered with the result that, for each additional unit of total charge delivered, there was an almost 8 times increase in the T15 time period (coefficient = 7.7, 95% CI=(6.5,8.9)) Conclusions: The increases in charge provided by longer PP and shorter PW produced significantly longer time of CPP &gt; 15 mm Hg within the limits of this test. Further study is required in order to further extend the duration of action ECPR.
Culture of endothelial cells from baboon and human glomeruli
Authors: Dollie Florence Green, Kay H. Hwang, Una S. Ryan, Jacques J. Bourgoignie, Jennifer Baker
Journal: Kidney International (1992)

Whereas mesangial and epithelial cells from glomeruli are commonly grown in vitro, there has been a failure to isolate and propagate human glomerular capillary endothelial cells. This study defines the conditions for the reproducible isolation and growth of homogeneous monolayers of primate (baboon and human) glomerular capillary endothelial cells. Using selective media and growth factors, the following criteria were identified to optimize the isolation and proliferation of glomerular endothelial cells: (1) collagenase treatment of isolated glomeruli; (2) requirement for 20% serum, endothelial cell growth factor and heparin; (3) requirement of fibronectin as surface matrix; and (4) isolation from donors less than 60 years old, as premature senescence was directly proportional to the age of the human kidney donor. Under these conditions, primary cultures with an endothelial cell composition greater than 70% were reproducibly obtained. Homogeneous endothelial monolayers were developed from 20 of 23 human kidneys, and maintained for 5 to 10 passages, depending on the age of the kidney donor. Purification to homogeneity was achieved by patch cloning or by fluorescence-activated cell sorting. Glomerular capillary endothelial cells exhibited a cobblestone morphology at confluence, expressed factor VIII-related antigen, angiotensin converting enzyme activity, and endocytosed acetylated low-density lipoproteins. Electron microscopy revealed the presence of intracellular Weibel-Palade bodies and caveolae and microvillous projections on the luminal surface. Glomerular cells also stained positive for Ulex europaeus, a lectin characteristic of human endothelial cells. In addition, preliminary results indicate that human glomerular endothelial cells increase intracellular cyGMP in response to alpha-human 5 to 28 atrial natriuretic peptide and intracellular free calcium in response to thrombin.
Preventing Neonatal Herpes-Reply
Authors: Jeffrey P. Koplan
Journal: JAMA (1985)

<h3>In Reply.—</h3> We applaud Dr Feldman's detailed efforts to reanalyze the maternal mortality data from our decision analysis on the value of viral cultures in preventing neonatal herpes. By definition, the tool of decision analysis is intended to stimulate constructive exchange over medical issues involving uncertainty. Dr Feldman has suggested using the mortality rate among women with repeated cesarean deliveries to calculate mortality among women whose indication for cesarean delivery is positive herpes culture. For several reasons, we feel that this rate is too low. First, this rate was obtained from a study that may have involved considerable underreporting. Second, because many women with positive cultures would have a cesarean delivery only after going into labor, a large portion of these operations would carry a greater risk to the woman than elective cesarean delivery. Finally, we do not feel that women with previous herpes infection who undergo cesarean delivery are
Understanding controlled trials: Crossover trials
Authors: B. Sibbald, C. Roberts
Journal: BMJ (1998)

This is the fifth of an occasional series on the methods of randomised controlled trials

In a crossover trial subjects are randomly allocated to study arms where each arm consists of a sequence of two or more treatments given consecutively. The simplest model is the AB/BA study. Subjects allocated to the AB study arm receive treatment A first, followed by treatment B, and vice versa in the BA arm. Crossover trials allow the response of a subject to treatment A to be contrasted with the same subject's response to treatment B. Removing patient variation in this way makes crossover trials potentially more efficient than similar sized, parallel group trials in which each subject is exposed to only one treatment. In theory treatment effects can be estimated with greater precision given the same number of subjects.

Crossover …
IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase
Authors: A B A Laranjeira, J F de Vasconcellos, L Sodek, M C Spago, M C Fornazim, L G Tone, S R Brandalise, A E Nowill, J A Yunes
Journal: Leukemia (2011)
A randomized comparison of the effects of gradual prolonged versus standard primary balloon inflation on early and late outcome. Results of a multicenter clinical trial. Perfusion Balloon Catheter Study Group.
Authors: E M Ohman, J F Marquis, D R Ricci, R I Brown, M L Knudtson, D J Kereiakes, J K Samaha, J R Margolis, A L Niederman, L S Dean
Journal: Circulation (1994)

BACKGROUND Observational studies have suggested that prolonged balloon inflation during coronary angioplasty is associated with a high clinical success rate. This randomized clinical trial sought to evaluate the impact of primary gradual and prolonged inflations versus standard short dilatations in patients undergoing elective angioplasty. METHODS AND RESULTS In phase 1 of the study, patients were randomized to receive two to four standard (1 minute) dilatations or one or two prolonged (15 minutes) dilatations after a perfusion balloon had been placed across a single target lesion. Patients with unsuccessful angiographic appearance after phase 1 dilatations had further dilatations in phase 2. Patients were followed for 6 to 12 months after the procedure. Of 478 patients, 242 received a median of one prolonged dilatation of 15 minutes' duration, and 236 received three dilatations for a median of 1 minute. Patients assigned to prolonged dilatations had a higher success rate (&lt; or = 50% residual visual stenosis) (95% versus 89%; P = .016), less severe residual stenosis by quantitative angiography (median [25th and 75th percentiles], 35% [26%, 42%] versus 38% [30%, 46%]; P = .001), and a lower rate of major dissections (3% versus 9%; P = .003) at the end of phase 1. A total of 114 patients had further dilatations in phase 2-43 in the prolonged arm and 71 in the standard arm. The final procedural success rate was 98% with both primary dilatation strategies, which included additional maneuvers such as prolonged dilatations in the patients randomized to the primary standard dilatation. Overall, 320 of 416 patients (77%) who were discharged after a successful procedure without any in-hospital event (death, myocardial infarction, coronary artery bypass graft surgery, abrupt closure, or repeat angioplasty in target vessel) returned for follow-up angiography. The restenosis rate (&gt; 50% residual visual stenosis) was 44% (95% confidence interval, 37% to 52%) in the prolonged dilatation group and 44% (36% to 52%) in the standard dilatation group. The primary angiographic end point of failure at the end of phase 1, abrupt closure, or restenosis throughout the study period was similar in both groups (prolonged, 51%; standard, 49%; P = .62). The secondary end point of absence of clinical events (death, nonfatal myocardial infarction, coronary artery bypass graft surgery, or repeat angioplasty in target vessel) also was similar (prolonged, 66%; standard, 74%; P = .15). CONCLUSIONS Primary gradual and prolonged dilatations caused less arterial trauma with a modestly larger arterial lumen compared with standard dilatations. This initial improvement in angiographic appearance did not lead to a significant reduction in restenosis or clinical adverse events during follow-up.
Drugs and Surgery in the Prevention of Ischemic Stroke
Authors: Henry J.M. Barnett, Michael Eliasziw, Heather E. Meldrum
Journal: New England Journal of Medicine (1995)

Randomized clinical trials have proved that warfarin therapy decreases the risk of stroke in patients with nonvalvular atrial fibrillation and in those who have had a myocardial infarction. In patients who are not candidates for long-term anticoagulant therapy, aspirin is beneficial, but the reduction in risk is smaller with aspirin than with warfarin. In patients with cerebral ischemic symptoms of noncardiac origin, aspirin and ticlopidine reduce the risk of stroke, but the benefit is modest. Given alone, neither dipyridamole nor sulfinpyrazone prevents stroke. The question remains whether either of these drugs plus aspirin is better than aspirin alone. The optimal dose of aspirin for stroke prevention has not been established. Carotid endarterectomy reduces the risk of stroke in symptomatic patients with at least 70 percent stenosis, as determined by arteriography. Current trials are addressing the question of whether endarterectomy is beneficial for patients with moderate degrees of carotid stenosis. The benefit of endarterectomy for patients with asymptomatic carotid lesions remains unclear.
Living with vitiligo: results from a national survey indicate differences between skin phototypes
Authors: K. Ezzedine, P.E. Grimes, J.‐M. Meurant, J. Seneschal, C. Léauté‐Labrèze, F. Ballanger, T. Jouary, C. Taïeb, A. Taïeb
Journal: British Journal of Dermatology (2015)

Funding sources: Funding support for editorial assistance was provided by Pierre Fabre SA, France. Conflicts of interest: C.T. is employed by Pierre Fabre SA. Dear Editor, Vitiligo, an acquired, idiopathic skin disease characterized by a generally progressive loss of inherited skin colour, has an estimated worldwide prevalence of 0·5–1%.1 2 Although vitiligo is more noticeable in individuals with dark skin, the prevalence is similar to that in the overall population.3 Despite not being life threatening, vitiligo is a serious skin disorder and the overall disease burden in individuals with vitiligo is often underestimated.3 The current study determined the burden, in the broadest sense (including impact on quality of life, self‐perceived stress and self‐image) of vitiligo on daily life and, in particular, assessed differences in the perception of vitiligo and its management in fair vs. dark skin phototypes. We conducted a cross‐sectional monocentric study in 300 patients with vitiligo, within the framework of developing a new specific vitiligo burden questionnaire. Consulting dermatologists recorded patient demographic/clinical characteristics, and classified patients as having 'fair skin' (phototype I–III) or 'dark skin' (phototype IV–VI). This study was approved by the Commission Nationale Informatique et Libertés and by the local ethics committee of the University Hospital of Bordeaux.
Treatment of Cancer of the Larynx-Reply
Authors: A. Robert Kagan
Journal: JAMA (1982)

In Reply.—  I believe that irradiation is the method of choice for T1 and T2 carcinomas of the vocal cord. The cure with radiation alone is in excess of 85% with present-day treatment techniques and increases in excess of 95% with surgical salvage. 1 I think that the quality of a patient's voice after radiation for invasive cancer is superior to that of partial laryngeal surgery. I would presume that, as with most historical series, neither adequate dose nor proper portal placement was used in many of this author's 147 patients.  We are in agreement with Dr Miller that carcinoma in situ is best managed by surgery, but we have shown that irradiation can also be highly successful. 2   Legitimate differences of opinion exist in many aspects of the management of head and neck tumors. 3 Exchange of views such as this is of educational interest to physicians, which always