tbuckley/cabot-search huggingface dataset:
Children's Hospital, Paris: Acute Rheumatism -- Pericarditis -- Sudden Death
Authors: P. H. Green
Journal: BMJ (1842)

years of age, was admitted into hospital October 11.For some time past the child had complained of wandering pains in the limbs, but not sufficiently severe to prevent him from working at his trade.On the 8th and 9th he experienced a general sense of fatigue, with headache, pain in the muscles of the neck, and uneasiness during the act of swallowing; in the night of the 9th the ancle-joints became red, swollen, and excessively painful; general febrile symptoms set in; and in the morning the elbow-joints were attacked in a similar manner.Oct. 12.The child complains of headache; the face is red, and expressive of pain; the least move- ment makes him cry out; the knee-joints and the left ancle are red, swollen, and painful; there is pain, without swelling or redness, in the hip-joints, and in the right shoulder-joint; he also complains of severe pam in the muscles of the neck, and is unable to move his head; skin hot, but moist; pulse 112; bowels confined; no vomiting.He was ordered to have poultices to the joiits and frictions with an anodyne liniment along the thighs.13. Passed a restless night; the knee and ancle- joints are less swollen; the wrist-joints are now attacked, and likewise the left elbow-joint; the
Combined Use of Exhaled Hydrogen Peroxide and Nitric Oxide in Monitoring Asthma
Authors: ILDIKÓ HORVÁTH, LOUISE E. DONNELLY, ANDRÁS KISS, SERGEI A. KHARITONOV, SAM LIM, K. FAN CHUNG, PETER J. BARNES
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Oxidative stress contributes to airway inflammation and exhaled hydrogen peroxide (H2O2) and nitric oxide (NO) are elevated in asthmatic patients. We determined the concentrations of expired H2O2 and NO in 116 asthmatic (72 stable steroid-naive, 30 stable steroid-treated, and 14 severe steroid-treated unstable patients) and in 35 healthy subjects, and studied the relation between exhaled H2O2, NO, FEV1, airway responsiveness, and eosinophils in induced sputum. Both exhaled H2O2 and NO levels were elevated in steroid-naive asthmatic patients compared with normal subjects (0.72 +/- 0.06 versus 0.27 +/- 0.04 microM and 29 +/- 1.9 versus 6.5 +/- 0. 32 ppb, respectively; p < 0.001) and were reduced in stable steroid-treated patients (0.43 +/- 0.08 microM, p < 0.05, and 9.9 +/- 0.97 ppb, p < 0.001). In unstable steroid-treated asthmatics, however, H2O2 levels were increased, but exhaled NO levels were low (0.78 +/- 0.16 microM and 6.7 +/- 1.0 ppb, respectively). There was a correlation between expired H2O2, sputum eosinophils and airway hyperresponsiveness (methacholine PC20). Exhaled NO also correlated with sputum eosinophils, but not with airway hyperresponsiveness. Our findings indicate that measurement of expired H2O2 and NO in asthmatic patients provides complementary data for monitoring of disease activity.
Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA)
Authors: Marta Ugarte, Marie Brown, Katherine A Hollywood, Garth J Cooper, Paul N Bishop, Warwick B Dunn
Journal: Genome Medicine (2012)

Abstract Background The prevalence, and associated healthcare burden, of diabetes mellitus is increasing worldwide. Mortality and morbidity are associated with diabetic complications in multiple organs and tissues, including the eye, kidney and cardiovascular system, and new therapeutics to treat these complications are required urgently. Triethylenetetramine (TETA) is one such experimental therapeutic that acts to chelate excess copper (II) in diabetic tissues and reduce oxidative stress and cellular damage. Methods Here we have performed two independent metabolomic studies of serum to assess the suitability of the streptozotocin (STZ)-induced rat model for studying diabetes and to define metabolite-related changes associated with TETA treatment. Ultraperformance liquid chromatography-mass spectrometry studies of serum from non-diabetic/untreated, non-diabetic/TETA-treated, STZ-induced diabetic/untreated and STZ-induced diabetic/TETA-treated rats were performed followed by univariate and multivariate analysis of data. Results Multiple metabolic changes related to STZ-induced diabetes, some of which have been reported previously in other animal and human studies, were observed, including changes in amino acid, fatty acid, glycerophospholipid and bile acid metabolism. Correlation analysis suggested that treatment with TETA led to a reversal of diabetes-associated changes in bile acid, fatty acid, steroid, sphingolipid and glycerophospholipid metabolism and proteolysis. Conclusions Metabolomic studies have shown that the STZ-induced rat model of diabetes is an appropriate model system to undertake research into diabetes and potential therapies as several metabolic changes observed in humans and other animal models were also observed in this study. Metabolomics has also identified several biological processes and metabolic pathways implicated in diabetic complications and reversed following treatment with the experimental therapeutic TETA.
Predicting the outcome from NIV for acute exacerbations of COPD
Authors: J V J LIGHTOWLER
Journal: Thorax (2000)

The use of non-invasive ventilation (NIV) in the management of acute exacerbations of chronic obstructive pulmonary disease (COPD) is now supported by a number of randomised controlled trials.1-5 It has been shown to reduce intubation rates,1 3-5 mortality,1 2-5 and length of stay.1 4 It has the advantage that it can be applied intermittently, avoids the need for sedation, and allows the patient to eat, drink and talk. The incidence of nosocomial pneumonia during NIV is lower than in intubated patients.6-8 NIV has the additional advantage that it can be used with success outside the intensive care unit (ICU), thereby reducing the demand on ICU beds.5 

However, NIV is not without its problems. The mask can be uncomfortable and claustrophobic for an acutely dyspnoeic patient, it can cause facial skin necrosis and, if poorly fitted, may be associated with large amounts of leakage which may compromise the efficiency of ventilation. Gastric distension is also recognised. Without the presence of an endotracheal/tracheostomy tube the lower airway cannot be easily accessed which makes bronchial toilet difficult. NIV is not successful in all cases of acute on chronic respiratory failure due to COPD, with reported failure rates of 7–50%.4 9 There has also been concern that NIV may delay intubation leading to a worse outcome.10 11 

The ability to predict those likely to fail with NIV is important. Patients in whom there is a high likelihood of failure would be spared the discomfort of a trial of NIV and intubation would not be delayed. It would also be helpful in determining where NIV should take place; a patient with a high likelihood of failing, and for whom intubation would be considered appropriate, is best managed in the ICU, whereas the patient who is likely to …
Hyaloraphidium curvatum: A Linear Mitochondrial Genome, tRNA Editing, and an Evolutionary Link to Lower Fungi
Authors: Lise Forget, Jana Ustinova, Zhang Wang, Volker A R Huss, B Franz Lang
Journal: Molecular Biology and Evolution (2002)

We have sequenced the mitochondrial DNA (mtDNA) of Hyaloraphidium curvatum, an organism previously classified as a colorless green alga but now recognized as a lower fungus based on molecular data. The 29.97-kbp mitochondrial chromosome is maintained as a monomeric, linear molecule with identical, inverted repeats (1.43 kbp) at both ends, a rare genome architecture in mitochondria. The genome encodes only 14 known mitochondrial proteins, 7 tRNAs, the large subunit rRNA and small subunit rRNA (SSU rRNA), and 3 ORFs. The SSU rRNA is encoded in two gene pieces that are located 8 kbp apart on the mtDNA. Scrambled and fragmented mitochondrial rRNAs are well known from green algae and alveolate protists but are unprecedented in fungi. Protein genes code for apocytochrome b; cytochrome oxidase 1, 2, and 3, NADH dehydrogenase 1, 2, 3, 4, 4L, 5, and 6, and ATP synthase 6, 8, and 9 subunits, and several of these genes are organized in operon-like clusters. The set of seven mitochondrially encoded tRNAs is insufficient to recognize all codons that occur in the mitochondrial protein genes. When taking into account the pronounced codon bias, at least 16 nuclear-encoded tRNAs are assumed to be imported into the mitochondria. Three of the seven predicted mitochondria-encoded tRNA sequences carry mispairings in the first three positions of the acceptor stem. This strongly suggests that these tRNAs are edited by a mechanism similar to the one seen in the fungus Spizellomyces punctatus and the rhizopod amoeba Acanthamoeba castellanii. Our phylogenetic analysis confirms with overwhelming support that H. curvatum is a member of the chytridiomycete fungi, specifically related to the Monoblepharidales.
Quantitative determination of regional oxygen consumption in the dog heart.
Authors: H R Weiss, J A Neubauer, J A Lipp, A K Sinha
Journal: Circulation Research (1978)

A micro-Fick method has been developed to measure the O2 consumption of different regions of an organ. The method was tested in isolated dog gracilis muscle and consisted of microspectrophotometric determination of arterial and venous O2 saturation in quick frozen tissue to determine O2 extraction and flow measured with 85Sr-labeled microspheres, with O2 consumption calculated from the product. This was compared to electromagnetically measured flow and O2 extraction determined by Van Slyke or CO-oximeter. The accuracy of the new measurement was at worst 8.7% for O2 consumption over the range tested in a single muscle. In the hearts of anesthetized open-chest dogs, right ventricular O2 consumption, 7.1 +/- 0.9 ml O2/min per 100 g, was significantly lower than left, 11.0 +/- 0.4. This gradient was related to a blood flow difference. Right ventricular base had a 51% lower O2 consumption than right ventricular apex. In the left ventricle, subepicardial O2 consumption, 9.5 +/- 0.7, was lower than that of the subenocardium, 12.1 +/- 0.7. This difference was related to a difference in O2 extraction.
Lack of Effect of Guideline Changes on Hypertension Control for Patients With Diabetes in the U.S., 1995–2005
Authors: Y. Richard Wang
Journal: Diabetes Care (2006)

To study the effect of new Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) guidelines on hypertension control for patients with diabetes in the U.S. using patients without diabetes as the control group for the time trend.The JNC VI and VII guidelines, published in 1997 and 2003, set more aggressive goal blood pressure for patients with diabetes. Data from the National Disease and Therapeutic Index, a nationally representative survey of outpatient visits in the U.S., was used to compare the difference in hypertension control (blood pressure <140/90 mmHg) between diabetic and nondiabetic visits during 1995-2005.Hypertension control improved for both diabetic and nondiabetic visits in the study period. Compared with nondiabetic visits, there was no change in hypertension control for diabetic visits before 2001 and an approximately 4% increase afterward (P < 0.001).The publication of new JNC guidelines did not result in substantially better hypertension control for patients with diabetes in the U.S.
An Evolutionary Model for Protein-Coding Regions with Conserved RNA Structure
Authors: Jakob Skou Pedersen, Roald Forsberg, Irmtraud Margret Meyer, Jotun Hein
Journal: Molecular Biology and Evolution (2004)

Here we present a model of nucleotide substitution in protein-coding regions that also encode the formation of conserved RNA structures. In such regions, apparent evolutionary context dependencies exist, both between nucleotides occupying the same codon and between nucleotides forming a base pair in the RNA structure. The overlap of these fundamental dependencies is sufficient to cause "contagious" context dependencies which cascade across many nucleotide sites. Such large-scale dependencies challenge the use of traditional phylogenetic models in evolutionary inference because they explicitly assume evolutionary independence between short nucleotide tuples. In our model we address this by replacing context dependencies within codons by annotation-specific heterogeneity in the substitution process. Through a general procedure, we fragment the alignment into sets of short nucleotide tuples based on both the protein coding and the structural annotation. These individual tuples are assumed to evolve independently, and the different tuple sets are assigned different annotation-specific substitution models shared between their members. This allows us to build a composite model of the substitution process from components of traditional phylogenetic models. We applied this to a data set of full-genome sequences from the hepatitis C virus where five RNA structures are mapped within the coding region. This allowed us to partition the effects of selection on different structural elements and to test various hypotheses concerning the relation of these effects. Of particular interest, we found evidence of a functional role of loop and bulge regions, as these were shown to evolve according to a different and more constrained selective regime than the nonpairing regions outside the RNA structures. Other potential applications of the model include comparative RNA structure prediction in coding regions and RNA virus phylogenetics.
Abstract 5282: Leptin induces Notch in endothelial cells: Role of VEGFR-2 transactivation
Authors: Viola Lanier, Corey Gillespie, Tanisha McGlothen, Toi Dickson, Shanchun Guo, Ruben R. Gonzalez-Perez
Journal: Cancer Research (2012)

Abstract Notch signaling is essential for breast cancer (BC) angiogenesis and its dysfunction is implicated in many cancers. Leptin (a pro-angiogenic, pro-inflammatory and mitogenic factor) induces the expression of VEGF/VEGFR-2 and Notch in BC cells. Moreover, the binding of leptin to its receptor (OB-Rb) in endothelial cells (EC) was shown to phosphorylate/transactivate VEGFR-2 inducing angiogenic features. We hypothesize that leptin is an inducer of Notch in EC and that this effect could occur upon leptin-mediated transactivation of VEGFR-2, thereby inducing angiogenic changes in EC. To this end, HUVEC cells were challenged with leptin, leptin inhibitor (LPrA2) VEGFR-2 kinase inhibitor (SU5416) and Notch signaling inhibitor (DAPT). Leptin-dose and time-course effects on expression of Notch (receptors: Notch1, Notch2, Notch3 and Notch4; ligands: JAG1, Dll-4 and targets: survivin and Hey2) were determined by WB and real time RT-PCR. The impact of LPrA2, SU5416 and DAPT on leptin-induced VEGFR-2 phosphorylation and Notch expression was also determined. The effects of leptin and inhibitors on EC proliferation, migration and tube formation were investigated. Results from our studies show for the first time that leptin is a potent inducer of Notch signaling in EC. Moreover, leptin-induced VEGFR-2 phosphorylation was closely related to leptin effects on Notch and the angiogenic features of EC. Therefore, leptin secreted either by adipose tissue or BC cells may contribute to tumor angiogenesis by acting directly on cancer cells inducing VEGF secretion or through EC inducing VEGFR-2/Notch crosstalk. Present results underline the notion that combinatory therapies targeting both Notch and leptin signaling could be a new strategy for BC treatment. [This work was supported in part by NIH/NCI1SC1CA138658-02; NIH/ARRA/3SC1CA138658-02S1 and the Georgia Cancer Coalition Distinguished Cancer Scholar Award (to RRGP)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5282. doi:1538-7445.AM2012-5282
Combined therapy with cisapride and cimetidine in severe reflux oesophagitis: a double blind controlled trial.
Authors: J P Galmiche, G Brandstatter, M Evreux, E Hentschel, E Kerstan, P Kratochvil, W Reichel, K Schutze, J C Soule, J Vitaux
Journal: Gut (1988)

Combined treatment with cimetidine 1 g daily and cisapride 40 mg daily in patients with endoscopically diagnosed severe reflux oesophagitis was compared with single drug therapy (cimetidine and placebo). At the end of the six to 12 weeks treatment, 11 (46%) of the 24 patients under single drug therapy were endoscopically healed and three were improved. In contrast, 16 (70%) of the 23 patients under combined therapy were healed and all of the remainder were improved (p = 0.025). The severity of diurnal and nocturnal heartburn, decreased significantly more (p less than 0.05) on cimetidine + cisapride than on cimetidine + placebo. The combined treatment was well tolerated. These results suggest that combined therapy with cisapride and cimetidine may be useful in patients with severe reflux oesophagitis.
Hepatic metabolism of 3 alpha-hydroxy-5 beta-etianic acid (3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acid) in the adult rat.
Authors: J M Little, J St Pyrek, R Lester
Journal: Journal of Clinical Investigation (1983)

Normal human meconium has been shown to contain short-chain (C20-C22) bile acids and, recently, these compounds have been identified in sera of patients with cholestasis. This suggests that shortchain bile acids may be secreted in bile. We have examined this point by studying the hepatic metabolism and biliary secretion of one naturally occurring C20 bile acid, 3 alpha-hydroxy-5 beta-etianic acid (3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acid). [3-3H]-3 alpha-hydroxy-5 beta-etianic acid was prepared and administered intravenously to rats prepared with an external biliary fistula. 85.5 +/- 1.2% of the administered dose was recovered in bile over 20 h with 71.5 +/- 1.3% appearing in the first hour. 11.9 +/- 1.6% of the dose was estimated to be distributed in body water and 0.6 +/- 0.2% was recovered as organic matter in urine. Total recovery of label was 98.0 +/- 2.6%. Administration of milligram quantities of 3 alpha-hydroxy-5 beta-etianic acid produced an increase in bile flow (58.9 +/- 7.1% over basal levels) within 20 min after injection of the steroid. The radiolabeled material in bile was shown by thin-layer chromatography (TLC) to be a polar conjugate which, after beta-glucuronidase hydrolysis, cochromatographed with authentic free 3 alpha-hydroxy-5 beta-etianic acid. After purification, and derivatization, the steroid moiety was proven by gas chromatography-mass spectrometry to be identical to 3 alpha-hydroxy-5 beta-etianic acid. Characterization of the conjugate by TLC and by 3 alpha-hydroxysteroid dehydrogenase assay, before and after beta-glucuronidase hydrolysis, indicated that the steroid was secreted in bile as the 3-O-beta-glucuronide. It is concluded that 3 alpha-hydroxy-5 beta-etianic acid is cleared from the plasma, conjugated with glucuronic acid, and secreted into bile rapidly and in high concentration. The choleretic properties of this shortchain bile acid contrast with the cholestatic effects of lithocholic acid, its C24 analog. Both the form of conjugation of etianic acid and its effect on bile flow suggest that the shortened side chain of this steroid markedly alters its hepatic metabolism and physiology.
Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery
Authors: Martin B. Leon, Craig R. Smith, Michael Mack, D. Craig Miller, Jeffrey W. Moses, Lars G. Svensson, E. Murat Tuzcu, John G. Webb, Gregory P. Fontana, Raj R. Makkar, David L. Brown, Peter C. Block, Robert A. Guyton, Augusto D. Pichard, Joseph E. Bavaria, Howard C. Herrmann, Pamela S. Douglas, John L. Petersen, Jodi J. Akin, William N. Anderson, Duolao Wang, Stuart Pocock
Journal: New England Journal of Medicine (2010)

Many patients with severe aortic stenosis and coexisting conditions are not candidates for surgical replacement of the aortic valve. Recently, transcatheter aortic-valve implantation (TAVI) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis.
Association of primary biliary cirrhosis with human leukocyte antigen DPB1*0501 in Japanese patients
Authors: Takeshi Seki, Kendo Kiyosawa, Masao Ota, Seiichi Furuta, Hirofumi Fukushima, Eiji Tanaka, Kaname Yoshizawa, Toshiko Kumagai, Nobuhisa Mizuki, Asako And, Hidetoshi Inok
Journal: Hepatology (1993)

To investigate the relationship between distribution of human leukocyte antigen alleles and susceptibility to primary biliary cirrhosis among Japanese, we performed serological typing and human leukocyte antigen DP genotyping in 47 Japanese patients with primary biliary cirrhosis. Serologically, the frequency of human leukocyte antigen DQ3 was significantly higher in the patients than in healthy controls, whereas frequency of DR52 was significantly lower in the patients. Human leukocyte antigen DP genotyping using the polymerase chain reaction-restriction-fragment-length polymorphism method showed that the frequency of human leukocyte antigen DPB1*0501 (85.1%) was significantly higher in patients than in healthy controls but that the frequency of DPB1*0402 was significantly lower in patients. The positive association of human leukocyte antigen DPB1*0501 with primary biliary cirrhosis was stronger than that of serological human leukocyte antigen DQ3, which can be explained by its linkage to DPB1*0501. In addition, three of seven DPB1*0501-negative patients had DPB1*0202, suggesting that the human leukocyte antigen DPB1 amino-acid chain plays an important role in the immunogenesis of primary biliary cirrhosis among Japanese patients. Comparative analysis of amino acid sequences from DPB1 alleles indicated that a Leu at position 35 of the DPB1 chain likely contributes to the susceptibility to primary biliary cirrhosis among the Japanese.
Darzi review: GPs will face more competition
Authors: A. O'Dowd
Journal: BMJ (2008)

Radical changes are outlined in the Darzi review this week, which leaves GPs facing a very different future.

General practices may find themselves competing with nurse led social enterprise companies to provide services, and some patients with chronic diseases will be able to hold personal health budgets. Doctors are also going to have to publish “quality accounts,” and work more closely with local authorities.

The quality of service provided in primary care will dictate future funding, as it will in other parts of the NHS, and the report makes it clear that GPs will be scrutinised more closely than ever before to ensure that they provide better and ever improving services.

A “fairer” funding system will be developed, says the report, ensuring …