tbuckley/cabot-search huggingface dataset:
The valine catabolic pathway in human liver: Effect of cirrhosis on enzyme activities
Authors: K Taniguchi, T Nonami, A Nakao, A Harada, T Kurokawa, S Sugiyama, N Fujitsuka, Y Shimomura, S M Hutson, R A Harris, H Takagi
Journal: Hepatology (1996)

The activities of key enzymes in the valine catabolic pathway--branched-chain aminotransferase, branched-chain alpha-keto acid dehydrogenase complex, methacrylyl (MC)-coenzyme A (CoA) hydratase (crotonase), and 3-hydroxyisobutyryl-CoA (HIB-CoA) hydrolase--were measured in normal and cirrhotic human livers. Unlike rat liver, which does not contain branched-chain aminotransferase, the aminotransferase activity in the normal liver was measurable and is increased somewhat in cirrhosis of the human liver. The total activity of branched-chain alpha-keto acid dehydrogenase complex in the normal human liver was approximately 1% of that in rat liver, and 20% to 30% of the complex was in the active form in both normal and cirrhotic livers. Only the actual activity of the enzyme was significantly decreased by cirrhosis. These results suggest that human liver is less active than rat liver in the catabolism of branched-chain amino and alpha-keto acids. Activities of MC-CoA hydratase and HIB-CoA hydrolase in human liver were very high compared with that of branched-chain alpha-keto acid dehydrogenase complex, suggesting an important role for these enzymes in catabolism of a potentially toxic compound, MC-CoA, formed as an intermediate in the catabolism of valine and isobutyrate. Cirrhosis resulted in a significant decrease in HIB-CoA hydrolase activity but had no effect on the citrate synthase activity, suggesting that the decrease in HIB-CoA hydrolase activity does not reflect a general decrease in mitochondria but that it may contribute to cellular damage that culminates in liver failure.
Cancer-killing Viruses Assist Gene Therapies
Authors: V. Brower
Journal: JNCI Journal of the National Cancer Institute (2008)

I n the beginning of the last century, scientists were surprised to discover that cancer patients infected with a viral illness sometimes experienced tumor regressions, as did patients given attenuated viral vaccines. By the end of the century, researchers performing early gene therapy experiments were using viruses as delivery vehicles, or vectors, to insert genes into cells, taking advantage of the viruses’ innate ability to infect cells, replicate, cause cell death, release viral particles, and spread. “In the fi rst human gene therapy trials in the 1990s, only nonreplicating viruses were used as vectors because of safety concerns,” said Evanthia Galanis, M.D., professor of oncology at the Mayo Clinic in Rochester, Minn. “This taught us an important lesson: Using nonreplicating viruses resulted in infection or therapeutic gene expression in only a small percentage of tumor cells. “Modifying viruses in a smart way to enable them to replicate and be as cancer specifi c as possible, while sparing normal cells, was the next step,” Galanis said. Because of these early trials, oncolytic, or cancer-killing, tumor viruses are now one of the most active areas of gene therapy research in cancer, with several proof-ofprinciple studies ongoing. “Viruses can be reprogrammed into oncolytic vectors by combining three types of modifi cation: targeting, arming, and shielding,” said Michael Barry, Ph.D., professor of medicine at the Mayo Clinic. The idea is that a virus that can replicate only in cancer cells will multiply within the cells and kill them, releasing new copies of the virus to surrounding cells when they die, thereby infecting other tumor cells locally and at distant sites. Viruses used for oncolytic cancer therapy include adenoviruses, vaccinia, herpes simplex type 1, Newcastle disease virus, measles, retroviruses, vesicular stomatitis virus, and reoviruses.
Pressure-flow and pressure-volume relations in the entire pulmonary vascular bed of the dog determined by two-port analysis.
Authors: A A Shoukas
Journal: Circulation Research (1975)

To quantify the resistance and particularly the capacitance properties of the entire pulmonary vascular bed, isolated perfused lungs of nine dogs were studied. In each dog, with a fixed endotracheal pressure of 5 mm Hg, the arterial pressure-flow and pressure-volume relations were determined while venous pressure was fixed at constant values of 2, 5, and 8 mm Hg. In the same dogs, the venous pressure-flow and pressure-volume relations were also obtained when arterial pressure was fixed at constant values of 15 and 20 mm Hg. The arterial and venous pressure-flow relations could be regarded as linear around the physiological ranges of arterial and venous pressures; however, at very low pressures, these relations became nonlinear. The arterial and venous pressure-volume relations were also approximately linear within the physiological pressure ranges. The mean arterial compliance was 0.1798 ml/mm Hg kg-1 and was independent of venous pressures. The venous compliance values were 0.1236 and 0.0955 ml/mm Hg kg-1 for arterial pressures of 15 and 20 mm Hg, respectively. The sums of the arterial and venous compliances were 0.3034 and 0.2753 ml/mm Hg kg-1 for arterial pressures of 15 and 20 mm Hg, respectively. These values were nearly identical to the mean total compliance, 0.3265 ml/mm Hg kg-1, measured in a separate series of experiments in the same dogs. Therefore, the data obtained in these experiments using two-port analysis techniques represent the compliances and the resistance of the entire pulmonary vascular bed around the normal operating pressures and flows.
Structural characteristics of Tla products.
Authors: M J Chorney, J S Tung, Y Bushkin, F W Shen
Journal: The Journal of Experimental Medicine (1985)

Biochemical study of thymus leukemia antigen (TL) from thymocytes of various Tla genotypes and from leukemia cells revealed features that, given present evidence, are peculiar to TL among class I products of the H-2:Qa:Tla region of chromosome 17. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of TL from thymocytes of all TL+ mouse strains, precipitated by anti-TL antiserum or monoclonal antibodies, showed two closely migrating bands of equal intensity in the heavy (H) chain position (45-50,000 mol wt). Comparison of these two bands by two-dimensional isoelectric focusing (2D IEF)-SDS-PAGE and 2D chymotryptic peptide mapping showed no differences indicative of protein dissimilarity. Thus, the two components of the H chain doublet may differ only in a feature of glycosylation that does not affect charge. The two leukemias studied gave only a single band in the H chain position. On 2D peptide mapping and 2D IEF-SDS-PAGE, the patterns for TL of Tlaa and Tlae thymocytes, which are closely related serologically, were broadly similar, but clearly different from the pattern typical of Tlac and Tlad thymocytes. 2D peptide maps of TL from Tlaa thymocytes and Tlaa leukemia cells did not differ. Leukemia cells of Tlab origin (thymocytes TL-) gave 2D peptide and 2D IEF-SDS-PAGE patterns of a third type. With the exception of Tlaa, thymocytes of TL+ mice yielded additional TL products of higher molecular weight than the TL H chain.
Tracheoesophageal Fistula Formation in Patients With Lung Cancer Treated With Chemoradiation and Bevacizumab
Authors: David R. Spigel, John D. Hainsworth, Denise A. Yardley, Eric Raefsky, Jeffrey Patton, Nancy Peacock, Cindy Farley, Howard A. Burris, F. Anthony Greco
Journal: Journal of Clinical Oncology (2009)

PURPOSE Tracheoesophageal fistulae are rare complications of thoracic cancers and their treatments. Novel antiangiogenic agents in cancer treatment such as bevacizumab potentially impact wound healing and may contribute to tracheoesophageal fistula development. PATIENTS AND METHODS We conducted two independent phase II clinical trials in small-cell lung cancer and non-small-cell lung cancer using bevacizumab in combination with chemotherapy and radiation. Both trials were intended to assess preliminary efficacy and safety outcomes. Results For the limited-stage small-cell lung cancer trial, 29 patients were enrolled beginning April 2006, and closed early due to toxicity in March 2007 (14-month median follow-up). The locally advanced, non-small-cell lung cancer trial opened with enrollment limited to five patients in February 2007, and closed early due to safety in December 2007. In each trial, we observed tracheoesophageal fistulae development and related morbidity and mortality, prompting early trial closures, US Food and Drug Administration warnings, and a change in bevacizumab labeling. CONCLUSION The current data from the final reports from these two trials suggest bevacizumab and chemoradiotherapy are associated with a relatively high incidence of tracheoesophageal fistulae formation in both small-cell lung cancer and non-small-cell lung cancer settings. Strategies to safely incorporate novel antiangiogenic agents into combined-modality therapy in lung cancer are needed.
Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial
Authors: C S J Probert
Journal: Gut (2003)

<b>Background:</b> Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn’s disease are established. We investigated its efficacy in ulcerative colitis. <b>Methods:</b> We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of ⩽2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later. <b>Results:</b> After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) <i>v</i> 5% (1/19) (95% confidence interval (CI) −9% to 24%); p=0.74). After six weeks, remission (UCSS ⩽2) rates were 39% (9/23) versus 30% (6/20) (95% CI −19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) <i>v</i> 30% (6/20) (95% CI −30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo. <b>Conclusion:</b> These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis.
S62 Risk Factors For Igra Positivity In Contacts Of Active Tuberculosis In A Uk High-prevalence Setting
Authors: A. Repossi, R. Turner, G. Bothamley
Journal: Thorax (2014)

<h3>Background</h3> Interferon-gamma release assays (IGRAs) are being used to confirm significant exposure to tuberculosis (TB) after a positive tuberculin skin test (TST). We explored the variability of a positive test in a large UK TB clinic amongst contacts of active disease. <h3>Methods</h3> The records of all individuals notified with active TB and of their screened contacts from 2012–3 were reviewed retrospectively. Uni- and multivariate analysis identified variables associated with active TB and/or QuantiFERON<sup>®</sup> test positivity in contacts. <h3>Results</h3> Of 203 notified tuberculosis index cases, 470 contacts were screened. 116 had immunological evidence of TB exposure including 11 with active disease. The estimated background rate of positive TB immune response was 18% and was the same in contacts of index cases who were later denotified (7/39) as in contacts of extrapulmonary disease (24/132). On univariate analysis, index case variables associated with a positive TST and IGRA were a pulmonary <i>vs.</i> extrapulmonary site of disease (OR 2.1; 95% confidence interval 1.3–3.5) and, for contacts of pulmonary TB (PTB), presence of cough (2.5; 1.1–4.0), duration of cough (p = 0.04),sputum smear positivity (1.7; 1.0–2.8), sputum smear grade (p = 0.02), radiographic extent of disease (p = 0.008), and perhaps pulmonary cavities (1.6; 1.0–2.6). No effect was detected of gender, smoking status, or TB strain of the index case (Beijing or Cameroon vs. other lineage), or nature of contact (household vs. other), even when considering only child contacts. Contact variables associated with positive tests were birth in a high TB prevalence country (2.3; 1.4–3.6), age ≥12 years (2.0; 1.2–3.3), smoking (2.2; 1.0–5.1) and perhaps alcohol excess (3.2; 0.9–10.7), but not diabetes or BCG vaccination. There were insufficient data to investigate an effect of HIV and homelessness. Contact country of birth (1.9; 1.1–3.1) and index site of disease (2.0; 1.2–3.4), sputum smear positivity (2.6; 1.3–5.6) and radiographic extent of disease (p = 0.008) remained significant on multi-variate analysis. <h3>Conclusion</h3> The likelihood of significant TB exposure is a consequence of bacillary load, radiographic extent of disease and coughing behaviour.
Instrumentation in Positron Emission Tomography
Authors: George M. Bohigian
Journal: JAMA (1988)

Positron emission tomography (PET) is a three-dimensional medical imaging technique that noninvasively measures the concentration of radiopharmaceuticals in the body that are labeled with positron emitters. With the proper compounds, PET can be used to measure metabolism, blood flow, or other physiological values in vivo. The technique is based on the physics of positron annihilation and detection and the mathematical formulations developed for x-ray computed tomography. Modern PET systems can provide three-dimensional images of the brain, the heart, and other internal organs with resolutions on the order of 4 to 6 mm. With the selectivity provided by a choice of injected compounds, PET has the power to provide unique diagnostic information that is not available with any other imaging modality. This is the first of five reports on the nature and uses of PET that have been prepared for the American Medical Association's Council on Scientific Affairs by an authoritative panel.  ( JAMA 1988;259:1531-1536)
PWE-105 Clinical efficacy of the combination of propofol and ketamine (ketofol) for deep sedation for colonoscopy
Authors: S Amornyotin, W Chalayonnawin, S Kongphlay
Journal: Gut (2012)

<h3>Introduction</h3> A combination of propofol and ketamine is usually used to achieve sedation and analgesia during colonoscopy. Few studies have compared their efficacy. The aim of this study was to compare and evaluate the clinical efficacy of the combination of propofol and ketamine (ketofol) vs propofol alone when each regimen is used as sedative agents for colonoscopy. <h3>Methods</h3> 194 patients who underwent colonoscopy in 2 years, were randomly assigned to PN and PK groups. 97 patients in group PN received propofol and normal saline and 97 patients in group PK received propofol and ketamine for intravenous sedation (IVS). All patients were premedicated with 0.02–0.03 mg/kg of midazolam. The primary outcome variable was the successfully completed colonoscopic procedure. The secondary outcome variables were patient tolerance, discomfort during insertion, patient and endoscopist satisfaction, haemodynamic responses, as well as complications during and immediately after procedure. Immediately after the procedure, the endoscopist was asked to rate tolerability for the patient, discomfort during insertion and satisfaction. As well, a blinded member of the research team evaluated the patient satisfaction, procedural pain, recovery time and recovery score. <h3>Results</h3> All endoscopies were completely successfully. Mean total dose of propofol in group PK and PN was 6.98 (2.90) mg/hg/h and 7.73 (3.45) mg/kg/h, respectively (p=0.413). Mean total dose of ketamine in group PK was 1.49 (0.61) mg/hg/h. There were no significant differences in patient tolerance, discomfort during insertion, patient and endoscopist satisfaction, haemodynamic responses, procedural pain, recovery time and recovery score. Overall, cardiovascular and respiratory adverse events were not significantly different between the two groups. These adverse events were transient and easily treated with no sequelae. <h3>Conclusion</h3> IVS in both regimens provided effective and safe for colonoscopy. Adverse events were relatively high in both groups. However, these adverse events were mild and transient. No serious adverse events were observed. <h3>Competing interests</h3> None declared.
Papillary Muscle Dysfunction in Coronary (Ischemic) Heart Disease
Authors: N P DePasquale, G E Burch
Journal: Annual Review of Medicine (1971)

Mitral value incompetence due to acquired or congenital disease of the mitral valve leaflets or to interruption of the chordae tendineae, has long been recognized, whereas valve incompetence secondary to disease of the papillary muscles has u ntil recently received little recognition. This review offers a brief discussion of papillary muscle dysfunction based upon studies from the Department of Medicine of the Tulane Medical School during the past 20 years (1-7).
Polymorphisms of the Protein Kinase C-β Gene (<i>PRKCB1</i>) Accelerate Kidney Disease in Type 2 Diabetes Without Overt Proteinuria
Authors: Shin-ichi Araki, Masakazu Haneda, Toshiro Sugimoto, Motohide Isono, Keiji Isshiki, Atsunori Kashiwagi, Daisuke Koya
Journal: Diabetes Care (2006)

We investigated the contribution of PKC-beta gene (PRKCB1) polymorphisms to diabetic kidney disease in a prospective observational follow-up study.A total of 364 Japanese subjects with type 2 diabetes without overt proteinuria were enrolled during 1996-1998 and followed until 2004. Five single nucleotide polymorphisms (-1504C/T, -546C/G, -348A/G, -278C/T, and -238C/G) in the promoter region of PRKCB1 were genotyped. The end points were transition from stage to stage of diabetic nephropathy as a time-to-event outcome and the annual decline rate of estimated glomerular filtration rate (eGFR) as a slope-based outcome.During the study (median 6 years), 34 of 364 subjects (9.3%) progressed. Kaplan-Meier estimation revealed that subjects with both T allele at -1054 C/T and G allele at -546 C/G polymorphisms frequently showed transition to advanced stages of diabetic nephropathy (P = 0.015). The annual change rate in eGFR in the subjects with both alleles was also significantly higher than in others (-2.96 +/- 0.62 vs. -1.63 +/- 0.15 ml/min per 1.73 m(2)/year, P = 0.02). The estimated frequency of this risk T-G haplotype was significantly higher in the progressors who showed transition to advanced nephropathy stages (12%) than in the nonprogressors (5%) (odds ratio 2.3 [95% CI 1.0-5.2]), and it was also higher in those with accelerated decline of the Delta eGFR (> or =3 ml/min per 1.73 m(2)/year) than in those without (2.1 [1.1-3.9]).Our study indicates that PRKCB1 is a predictor for worsening of kidney disease in Japanese subjects with type 2 diabetes.
Opposite Patterns of Left Ventricular Remodeling After Coronary Revascularization in Patients With Ischemic Cardiomyopathy
Authors: Vittoria Rizzello, Don Poldermans, Eric Boersma, Elena Biagini, Arend F.L. Schinkel, Boudewijn Krenning, Abdou Elhendy, Eleni C. Vourvouri, Fabiola B. Sozzi, Alexander Maat, Filippo Crea, Jos R.T.C. Roelandt, Jeroen J. Bax
Journal: Circulation (2004)

Background— In patients with ischemic cardiomyopathy, left ventricular (LV) remodeling is an important prognostic indicator. The precise relation between viable myocardium, revascularization, and ongoing or reversed remodeling is unknown and was evaluated in the present study. Methods and Results— A total of 100 patients with ischemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability and LV geometry (volumes and shape). At a mean of 10.2 months and 4.5 years after revascularization, resting echocardiography was repeated to evaluate LV remodeling. Long-term follow-up (mean 5±2 years) data were obtained. According to dobutamine stress echocardiography, 44 patients (44%) were defined as viable (≥4 viable segments) and 56 as nonviable. After revascularization, 40 patients (43%) had ongoing LV remodeling and 53 (57%) did not (in 7 patients who died early after revascularization, postoperative echocardiographic evaluation was not available). On multivariable analysis, the number of viable segments was the only predictor of ongoing LV remodeling (OR 0.60, 95% CI 0.48 to 0.75; P &lt;0.0001). The likelihood of LV remodeling decreased as the number of viable segments increased. During the follow-up, reverse remodeling was present in viable patients, whereas in nonviable patients, LV volumes significantly increased, which indicates ongoing LV remodeling. At follow-up, viable patients also showed a persistent improvement of heart failure symptoms and fewer cardiac events than nonviable patients ( P &lt;0.05). Conclusions— In patients with ischemic cardiomyopathy, a substantial amount of viable myocardium prevents ongoing LV remodeling after revascularization and is associated with persistent improvement of symptoms and better outcome.
Pediatric trauma: getting triage right
Authors: C. Di Scala
Journal: JAMA (1990)

To the Editor.—  I enjoyed reading the article entitled Evaluation of the Pediatric Trauma Score, 1 but I am having some problems with the authors' conclusions in relation to overtriaging and undertriaging of the two severity scores. While I agree that overtriaging (Pediatric Trauma Score more responsible than the Revised Trauma Score) is a serious problem, especially in these days of cost containment, I also think that undertriaging (Revised Trauma Score more responsible than the Pediatric Trauma Score) is an even more serious problem, given the consequences of inadequate medical care. There is more to the cost of trauma than just direct medical costs.  I was also puzzled by the extolling of the virtues of a triaging system with fewer parameters after a paragraph that seems to indicate that the Revised Trauma Score's undertriage rate could be improved by inclusion of specific injury criteria and evidence of high impact, thereby