tbuckley/cabot-search huggingface dataset:
Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time
Authors: H A J Gielkens, A van den Biggelaar, J Vecht, W Onkenhout, C B H W Lamers, A A M Masclee
Journal: Gut (1999)

Background Patients on total parenteral nutrition have an increased risk of developing gallstones because of gall bladder hypomotility. High dose amino acids may prevent biliary stasis by stimulating gall bladder emptying. Aims To investigate whether intravenous amino acids also influence antroduodenal motility. Methods Eight healthy volunteers received, on three separate occasions, intravenous saline (control), low dose amino acids (LDA), or high dose amino acids (HDA). Antroduodenal motility was recorded by perfusion manometry and duodenocaecal transit time (DCTT) using the lactulose breath hydrogen test. Results DCTT was significantly prolonged during LDA and HDA treatment compared with control. The interdigestive motor pattern was maintained and migrating motor complex (MMC) cycle length was significantly reduced during HDA compared with control and LDA due to a significant reduction in phase II duration. Significantly fewer phase IIIs originated in the gastric antrum during LDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control. Conclusions Separate intravenous infusion of high doses of amino acids in healthy volunteers: (1) modulates interdigestive antroduodenal motility; (2) shortens MMC cycle length due to a reduced duration of phase II with a lower contractile incidence both in the antrum and duodenum (phase I remains unchanged whereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3) prolongs interdigestive DCTT.
Heading in football, long-term cognitive decline and dementia: evidence from screening retired professional footballers
Authors: Simon Andrew Vann Jones, Richard William Breakey, Philip John Evans
Journal: British Journal of Sports Medicine (2013)

Background Heading impairs cognition in the short and medium-terms; however, little is known about the long-term consequences. This study aimed to investigate the hypothesis that chronic low-level head trauma is associated with persistent cognitive decline. Methods All members of Former Player Associations (FPAs) from four professional football clubs in the UK were contacted to participate in the study. Participants were required to complete a self-assessed test of cognition, the Test Your Memory questionnaire. Further information was collected from respondents in order to analyse the potential effect of a number of variables on cognition. Results 10 of 92 respondents (10.87%) screened positive for possible mild cognitive impairment (MCI) or dementia. There was no association between low-risk and high-risk playing positions (HR = 0.40, p = 0.456) or length of playing career (HR = 1.051 95% CI 0.879 to 1.257, p = 0.586) and a positive screening result. Age was a risk factor (HR = 1.137 per additional year, 95% CI 1.030 to 1.255, p &lt; 0.05), although this was not significantly different from the population prevalence across age groups. Conclusions These results suggest that once a player ends their playing career, their risk of harm falls in line with the population, suggesting either that changes are reversible or that heading may not be as harmful as commonly thought. Future longitudinal studies of large numbers of professional football players are needed to support the findings from this study.
Inhalation of Formalin in Catarrh and Other Diseases of the Respiratory Tract
Authors: J. L. Green
Journal: BMJ (1897)

depraved state of the appetite, and is a frequent symptom of eases of anaemia.According to Cobbold, it is a common symptom of worms of all kinds.I have at hand an extract from Dr. Livingstone's last Journals, Vol.ii, p. 83, which I think worth quoting:
Extensive cerebral infarction due to involvement of both anterior cerebral arteries by Wegener's granulomatosis.
Authors: J Satoh, N Miyasaka, T Yamada, T Nishido, M Okuda, T Kuroiwa, R Shimokawa
Journal: Annals of the Rheumatic Diseases (1988)

The central nervous system is often affected in Wegener9s granulomatosis (WG), but massive cerebral infarction due to occlusion of branches of the anterior cerebral arteries (ACA) by granulomatous lesions or thrombosis, or both, has seldom been reported. A case is reported here of a 67 year old man with WG complicated by generalised necrotising vasculitis in the lung, kidney, and gastrointestinal tract, and cerebral infarction in the territory of both anterior cerebral arteries, probably caused by thrombosis and a contiguous invasion of granulomatous lesion from the nasal cavity.
Modulation of Renal Calcium Handling by 11β-Hydroxysteroid Dehydrogenase Type 2
Authors: Paolo Ferrari, Mario G Bianchetti, Aurelie Sansonnens, Felix J Frey
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Reduced concentration of serum ionized calcium and increased urinary calcium excretion have been reported in primary aldosteronism and glucocorticoid-treated patients. A reduced activity of the 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) results in overstimulation of the mineralocorticoid receptor by cortisol. Whether inhibition of the 11βHSD2 by glycyrrhetinic acid (GA) may increase renal calcium excretion is unknown. Serum and urinary electrolyte and creatinine, serum ionized calcium, urinary calcium excretion, and the steroid metabolites (THF+5αTHF)/THE as a parameter of 11βHSD2 activity were repeatedly measured in 20 healthy subjects during baseline conditions and during 1 wk of 500 mg/d GA. One week of GA induced a maximal increment of 93% in (THF+5αTHF)/THE. Ambulatory BP was significantly higher at day 7 of GA than at baseline (126/77 ± 10/7 <i>versus</i> 115/73 ± 8/6 mmHg; <i>P</i> &lt; 0.001 for systolic; <i>P</i> &lt; 0.05 for diastolic). During GA administration, serum ionized calcium decreased from 1.26 ± 0.05 to 1.18 ± 0.04 mmol/L (<i>P</i> &lt; 0.0001), and absolute urinary calcium excretion was enhanced from 29.2 ± 3.6 to 31.9 ± 3.1 μmol/L GFR (<i>P</i> &lt; 0.01). Fractional calcium excretion increased from 2.4 ± 0.3 to 2.7 ± 0.3% (<i>P</i> &lt; 0.01) and was negatively correlated to the fractional sodium excretion during GA (<i>R</i> = −0.35; <i>P</i> &lt; 0.001). Moreover, serum potassium correlated positively with serum ionized calcium (<i>R</i> = 0.66; <i>P</i> &lt; 0.0001). Inhibition of 11βHSD2 activity is sufficient to significantly increase the fractional excretion of calcium and decrease serum ionized calcium, suggesting decreased tubular reabsorption of this divalent cation under conditions of renal glucocorticoid/mineralocorticoid excess. The likely site of steroid-regulated renal calcium handling appears to be the distal tubule. E-mail: paolo.ferrari@insel.ch
STUDIES ON A VIRUS FROM A PATIENT WITH FORT BRAGG FEVER (PRETIBIAL FEVER)
Authors: Hugh Tatlock
Journal: Journal of Clinical Investigation (1947)

During the summer of 1942, an outbreak of a dengue-like illness of unknown etiology occurred at Fort Bragg, North Carolina.The disease, described by Daniels and Grennan (1), was characterized by moderate prostration, fever, spleno- megaly, a rash localizing particularly on the anterior aspects of the legs, and a short course.The localization of the rash gave rise to the name "pretibial fever."Epidemiological information indicated that all of the patients in this outbreak were quartered in the same area of the post and that the incubation period was 10 days or longer.Serological tests served to exclude endemic typhus, infectious mononucleosis, brucellosis, and the typhoid-paratyphoid group of diseases.A commission was assigned by the Surgeon General of the United States Army to investigate the epidemiology and etiology of the disease.Working with frozen material in the form of blood, nasal washings, and urine from the patients, the members of the commission concluded: "All tests on this material proved negative as far as isolating or 1 Captain, MC, AUS.
Diameter of afferent arterioles during autoregulation estimated from microsphere data in the dog kidney.
Authors: L Mørkrid, J Ofstad, Y Willassen
Journal: Circulation Research (1978)

Afferent arteiolar diameters, relative flow distribution, and flow conductance factors are estimated by nonlinear regression analysis of the sieving effect on microspheres in different vascular structures of the dog renal cortex. The data presented are from experiments in which microspheres of 10-30 microgram were injected into the abdominal aorta during normotension and after lowering the blood pressure to the lower limit of autoregulation. Microscopic examination of the spheres trapped in the glomeruli and the renal arteries showed an increasing exclusion of microspheres greater than 15 micrometer from the afferent arterioles during normotension. This effect was most pronounced for the deeper cortical layers and can be explained mainly as geometrical exclusion of spheres from afferent arterioles. During hypotension, progressively larger microspheres entered glomeruli and afferent arterioles, presumably due to vasodilation of the vessels. There was a significant redistribution of microspheres larger than 15 micrometer from the outer to the inner cortex during hypotension without a corresponding redistribution of smaller spheres or the estimated blood flow. Approximately the same degree of dilation of afferent arterioles was observed during autoregulatory hypotension in three cortical layers.
STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing
Authors: Geethanjali Pickert, Clemens Neufert, Moritz Leppkes, Yan Zheng, Nadine Wittkopf, Moritz Warntjen, Hans-Anton Lehr, Sebastian Hirth, Benno Weigmann, Stefan Wirtz, Wenjun Ouyang, Markus F. Neurath, Christoph Becker
Journal: The Journal of Experimental Medicine (2009)

Signal transducer and activator of transcription (STAT) 3 is a pleiotropic transcription factor with important functions in cytokine signaling in a variety of tissues. However, the role of STAT3 in the intestinal epithelium is not well understood. We demonstrate that development of colonic inflammation is associated with the induction of STAT3 activity in intestinal epithelial cells (IECs). Studies in genetically engineered mice showed that epithelial STAT3 activation in dextran sodium sulfate colitis is dependent on interleukin (IL)-22 rather than IL-6. IL-22 was secreted by colonic CD11c+ cells in response to Toll-like receptor stimulation. Conditional knockout mice with an IEC-specific deletion of STAT3 activity were highly susceptible to experimental colitis, indicating that epithelial STAT3 regulates gut homeostasis. STAT3IEC-KO mice, upon induction of colitis, showed a striking defect of epithelial restitution. Gene chip analysis indicated that STAT3 regulates the cellular stress response, apoptosis, and pathways associated with wound healing in IECs. Consistently, both IL-22 and epithelial STAT3 were found to be important in wound-healing experiments in vivo. In summary, our data suggest that intestinal epithelial STAT3 activation regulates immune homeostasis in the gut by promoting IL-22–dependent mucosal wound healing.
Effects of substrates on tissue metabolic changes in the isolated rat heart during underperfusion and on release of lactate dehydrogenase and arrhythmias during reperfusion.
Authors: O L Bricknell, L H Opie
Journal: Circulation Research (1978)

In Langendorff-perfused rat hearts, the perfusion pressure was reduced from 100 cm H2O to 20 cm H2O for 30 minutes to produce a model of global ischemia with a residual oxygen uptake. The release of lactate dehydrogenase (LDH) and the occurrence of ventricular arrhythmias during reperfusion were dependent on the substrate. Glucose-perfused hearts had the highest rates of glycolytic ATP production (2.5 mumol/g per min) during ischemia with normal contents of tissue cyclic adenosine 3',5'-monophosphate (cAMP) and, during reperfusion, the release of LDH was lowest and severe ventricular arrhythmias did not occur. In pyruvate-perfused hearts, glycolysis was inhibited during ischemia, the rate of production of glycolytic ATP was only 0.5 mumol/g per min. and tissue cAMP doubled; during reperfusion, LDH release was 14-fold higher and ventricular arrhythmias were more severe. Total tissue contents of ATP and phosphocreatine were similar in glucose- and in pyruvate-perfused hearts. In hearts perfused with acetate, there was virtually no glycolytic ATP synthesized during the last 5 minutes of ischemia and cAMP increased further. Acetate- and palmitate-perfused hearts showed greatest release of LDH and had severest arrhythmias during reperfusion, suggesting that it was the metabolic and not the detergent effects of palmitate that were operating. Lipolysis was not a major factor in the cause of reperfusion LDH release. A role of glycolytic ATP in the maintenance of membrane integrity is postulated.
Dasatinib Inhibits the Growth of Molecularly Heterogeneous Myeloid Leukemias
Authors: Bella S. Guerrouahen, Muneyoshi Futami, Christos Vaklavas, Jukka Kanerva, Zakary L. Whichard, Kenechi Nwawka, Elisabeth G. Blanchard, Francis Y. Lee, Lisa J. Robinson, Robert Arceci, Steven M. Kornblau, Eric Wieder, Yvon E. Cayre, Seth J. Corey
Journal: Clinical Cancer Research (2010)

Dasatinib is a dual Src/Abl inhibitor recently approved for Bcr-Abl+ leukemias with resistance or intolerance to prior therapy. Because Src kinases contribute to multiple blood cell functions by triggering a variety of signaling pathways, we hypothesized that their molecular targeting might lead to growth inhibition in acute myeloid leukemia (AML).We studied growth factor-dependent and growth factor-independent leukemic cell lines, including three cell lines expressing mutants of receptor tyrosine kinases (Flt3 or c-Kit) as well as primary AML blasts for responsiveness to dasatinib.Dasatinib resulted in the inhibition of Src family kinases in all cell lines and blast cells at approximately 1 x 10(-9) mol/L. It also inhibited mutant Flt3 or Kit tyrosine phosphorylation at approximately 1 x 10(-6) mol/L. Mo7e cells expressing the activating mutation (codon 816) of c-Kit were most sensitive to growth inhibition with a GI(50) of 5 x 10(-9) mol/L. Primary AML blast cells exhibited a growth inhibition of <1 x 10(-6) mol/L. Cell lines that showed growth inhibition at approximately 1 x 10(-6) mol/L showed a G(1) cell cycle arrest and correlated with accumulation of p21 and p27 protein. The addition of rapamycin or cytotoxic agents enhanced growth inhibition. Dasatinib also caused the apoptosis of Mo7e cells expressing oncogenic Kit.Although all of the precise targets for dasatinib are not known, this multikinase inhibitor causes either growth arrest or apoptosis in molecularly heterogeneous AML. The addition of cytotoxic or targeted agents can enhance its effects.
Photothermal cancer therapy via femtosecond-laser-excited FePt nanoparticles
Authors: Cheng-Lung Chen, Ling-Ru Kuo, Shin-Yu Lee, Yeu-Kuang Hwu, Shang-Wei Chou, Chia-Chun Chen, Fu-Hsiung Chang, Kung-Hsuan Lin, Dzung-Han Tsai, Yang-Yuan Chen
Journal: Biomaterials (2012)
Adolescents and Their Music: Paganini, Satanists, and Insider Trading
Authors: John Di Saia
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The article by Drs Brown and Hendee<sup>1</sup>on music in adolescence addresses several salient points about the importance of music to the adolescent; however, in targeting heavy metal it becomes very much typical of the media's assault on this form of music. Drs Brown and Hendee direct their discussion toward a form of music that they never really define clearly. Is all music with a "loud beat and performers with aggressive and startling stage antics" heavy metal? In his age, Niccolò Paganini was known similarly. Then, is the work of Paganini heavy metal? As is typical of these discussions, the different categories within the genre are not identified (ie, power pop, hardcore/ thrash, progressive, and neoclassicalfusion). Is all heavy metal correlated with poor school performance? Drs Brown and Hendee cite Roe,<sup>2</sup>stating that "music preferences are dependent on earlier levels of school achievement." It seems
Proteinuria and Rate of Change in Kidney Function in a Community-Based Population
Authors: Tanvir Chowdhury Turin, Matthew James, Pietro Ravani, Marcello Tonelli, Braden J. Manns, Robert Quinn, Min Jun, Scott Klarenbach, Brenda R. Hemmelgarn
Journal: Journal of the American Society of Nephrology (2013)

Proteinuria identifies patients at risk for adverse clinical outcomes, but it is unclear whether proteinuria correlates with the rate of renal decline. We examined the association between proteinuria and rate of change in estimated GFR (eGFR) in a cohort of 638,150 adults from a province-wide registry in Alberta, Canada, who had a measure of proteinuria and three or more outpatient serum creatinine measurements over a period of ≥1 year. An adjusted sex-specific linear mixed-effects model was used to determine the rate of change in eGFR per year for patients with normal, mild, and heavy proteinuria, stratified by baseline kidney function (eGFR ≥90, 60–89.9, 45–59.9, 30–44.9, and 15–29.9 ml/min per 1.73 m2). In men, heavy proteinuria and a baseline eGFR of 45–59.9 ml/min per 1.73 m2 correlated with a change in eGFR of −2.16 (95% confidence interval [CI], −2.37 to −1.95) ml/min per 1.73 m2 per year, whereas mild proteinuria and a baseline eGFR of 30–44.9 ml/min per 1.73 m2 correlated with a change in eGFR of −0.51 (95% CI, −0.70 to −0.32) ml/min per 1.73 m2 per year. Similar trends were observed for female, elderly, and diabetic patients. Notably, normal protein levels and a lower baseline eGFR (15–29.9 ml/min per 1.73 m2) correlated with stable or improved renal function. In conclusion, our results suggest that proteinuria of increasing severity is associated with a faster rate of renal decline, regardless of baseline eGFR, and the combined effect should be considered in patients with CKD.
Apoptosis and Fas/Fas ligand mRNA expression in acute immune complex alveolitis in mice
Authors: Y Nomoto, K Kuwano, N Hagimoto, R Kunitake, M Kawasaki, N Hara
Journal: European Respiratory Journal (1997)

Deoxyribonucleic acid (DNA) strand breaks as a characteristic of apoptosis, and Fas antigen (Fas)/Fas ligand (FasL) expression may participate in acute immune complex alveolitis in mice. Male Institute for Cancer Research (ICR) mice were injected intravenously with immunoglobulin G (IgG) antibodies against ovalbumin and inhaled an aerosolized oval albumin (OA) solution. They were killed at 4, 6, 12, 24, 48 h and 7 days after aerosolization. We assessed DNA fragmentation by agarose gel electrophoresis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labelling (TUNEL). The expression of Fas and FasL messenger ribonucleic acid (mRNA) in lung tissues was assessed by reverse transcriptase (RT) polymerase chain reaction, and by in situ hybridization (ISH) to localize Fas mRNA, and RT in situ polymerase chain reaction to localize FasL mRNA. The fragmentation of DNA extracted from lung tissue was found 6-24 h after OA inhalation. TUNEL detected positive signals in bronchial and alveolar epithelial, endothelial and inflammatory cells in the lung tissue. These positive signals had disappeared 7 days after OA inhalation. TUNEL also detected positive signals in apoptotic neutrophils in bronchoalveolar lavage fluid at 6-12 h. Fas mRNA was expressed in the alveolar epithelial and inflammatory cells, while the expression of FasL mRNA appeared to be upregulated in infiltrating inflammatory cells at 6-24 h. These results suggest that apoptosis may be associated with the resolution of inflammation and with tissue repair and also suggest the involvement of the Fas antigen/Fas ligand pathway in acute immune complex alveolitis in mice.
Treating Electrical Storm
Authors: Koonlawee Nademanee, Richard Taylor, William E. Bailey, Daniel E. Rieders, Erol M. Kosar
Journal: Circulation (2000)

Electrical storm (ES), defined as recurrent multiple ventricular fibrillation (VF) episodes, often occurs in patients with recent myocardial infarction. Because treating ES according to the Advanced Cardiac Life Support (ACLS) guidelines yields a poor outcome, we evaluated the efficacy of sympathetic blockade in treating ES patients and compared their outcome with that of patients treated according to the ACLS guidelines.Forty-nine patients (36 men, 13 women, mean age 57+/-10 years) who had ES associated with a recent myocardial infarction were separated into 2 groups. Patients in group 1 (n=27) received sympathetic blockade treatment: 6 left stellate ganglionic blockade, 7 esmolol, and 14 propranolol. Patients in group 2 (n=22) received antiarrhythmic medication as recommended by the ACLS guidelines. Patient characteristics were similar in the 2 groups. The 1-week mortality rate was higher in group 2: 18 (82%) of the 22 patients died, all of refractory VF; 6 (22%) of the 27 group 1 patients died, 3 of refractory VF (P<0.0001). Patients who survived the initial ES event did well over the 1-year follow-up period: Overall survival in group 1 was 67%, compared with 5% in group 2 (P<0.0001).Sympathetic blockade is superior to the antiarrhythmic therapy recommended by the ACLS guidelines in treating ES patients. Our study emphasizes the role of increased sympathetic activity in the genesis of ES. Sympathetic blockade-not class 1 antiarrhythmic drugs-should be the treatment of choice for ES.
Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients
Authors: Jacob Nattermann, Martin Vogel, Thomas Berg, Mark Danta, Baumgarten Axel, Christoph Mayr, Raffaele Bruno, Christina Tural, Gerd Klausen, Bonaventura Clotet, Thomas Lutz, Frank Grünhage, Michael Rausch, Hans Dieter Nischalke, Knud Schewe, Bernhard Bienek, Georg Haerter, Tilman Sauerbruch, Juergen K. Rockstroh, Ulrich Spengler
Journal: Hepatology (2007)

Abstract Hepatitis C virus (HCV)/human immunodeficirency virus (HIV) coinfection poses a difficult therapeutic problem. Response to HCV-specific therapy is variable but might be influenced by host genetic factors, including polymorphisms of cytokine genes. Here, we studied whether interleukin-6 (IL-6) C174G gene polymorphism affects the response to antiviral treatment in HCV-infected HIV-positive subjects. We determined IL-6 genotypes in HIV-positive patients with acute (n = 52) and chronic (n = 60) hepatitis C treated with pegylated interferon-α. Two hundred ten HCV monoinfected, 197 HIV monoinfected, and 100 healthy individuals were studied as controls. Patients were classified into high and low producers according to IL-6 genotypes. Rates of sustained virological responses (SVRs) were compared between the IL-6 genotypes. Signal transducer and activator of transcription three phosphorylation was analyzed by Western blot in HCV core-transfected human hepatoma cell line (HUH7) cells. Distribution of IL-6 genotypes did not differ significantly between the study groups. SVR was achieved in 63% of HIV/HCV coinfected patients. Carriers of the IL-6 high producer (HP) genotype had significantly higher SVR rates than patients with an IL-6 low producer genotype (70.1% versus 52%; P &lt; 0.002). This effect was seen in both HIV-positive patients with acute (74% versus 33%; P &lt; 0.05) and chronic (66% versus 33%; P &lt; 0.05) hepatitis C. Multivariate analysis confirmed IL-6 HP carriage as an independent positive predictor for SVR (Odd′s ratio 6.1; P = 0.004). This effect corresponds to the in vitro observation that in HCV core-transfected HUH7 cells, IL-6 overcomes the HCV core-mediated inhibition of STAT3 activation. Conclusion: Response rates to HCV-specific treatment are higher in HCV/HIV-positive patients carrying the IL-6 HP genotype, which might be because of IL-6 mediated STAT3 activation. (HEPATOLOGY 2007.)