tbuckley/cabot-search huggingface dataset:
Satavaptan for the management of ascites in cirrhosis: efficacy and safety across the spectrum of ascites severity
Authors: Florence Wong, Hugh Watson, Alexander Gerbes, Hendrik Vilstrup, Salvatore Badalamenti, Mauro Bernardi, Pere Ginès
Journal: Gut (2011)

<h3>Objective</h3> Satavaptan, a vasopressin V2 receptor antagonist, has been shown to improve the control of ascites in cirrhosis in short-term phase II studies. The aim of this study was to evaluate the efficacy and safety of satavaptan in three different populations of patients with cirrhosis and ascites. <h3>Methods</h3> 1200 patients were included in three randomised double-blind studies comparing satavaptan with placebo in uncomplicated ascites (study 1: n=463 patients) and difficult-to-treat ascites, with and without concomitant diuretic treatment (studies 2 and 3: n=497 and n=240 patients, respectively). <h3>Results</h3> Satavaptan was not more effective than placebo in the control of ascites in any of the populations studied as estimated by the primary efficacy endpoints: worsening of ascites (study 1) and the cumulative number of large-volume paracenteses during 12 weeks (studies 2 and 3). Nevertheless, some of the secondary efficacy endpoints related to the treatment of ascites were met in the three studies, suggesting a slight advantage of satavaptan over placebo in delaying ascites formation. Moreover, satavaptan was more effective than placebo in improving the serum sodium concentration in patients with hyponatraemia. The incidence of major complications of cirrhosis during follow-up did not differ significantly between the satavaptan and placebo groups in the three studies. Overall, the rate of any treatment-related adverse events, serious treatment-related events and treatment-related events leading to permanent discontinuation of treatment did not differ significantly between the treatment groups. However, in study 2 mortality was higher in patients treated with satavaptan compared with placebo (HR 1.47; 95% CI 1.01 to 2.15); no significant differences in mortality between the two groups were observed in the other two studies. No specific cause for the increased mortality was identified. Most deaths were associated with known complications of liver cirrhosis. <h3>Conclusion</h3> Satavaptan, alone or in combination with diuretics, is not clinically beneficial in the long-term management of ascites in cirrhosis.
Safety, Clinical and Immunologic Efficacy of a Chinese Herbal Medicine (FAHF-2) for Food Allergy
Authors: Julie Wang, Stacie M. Jones, Jacqueline A. Pongracic, Ying Song, Nan Yang, Scott H. Sicherer, Melanie M. Makhija, Rachel Glick Robison, Erin Moshier, James Godbold, Hugh A. Sampson, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2015)
The Life and Death of Epithelia During Inflammation: Lessons Learned from the Gut
Authors: Stefan Koch, Asma Nusrat
Journal: Annual Review of Pathology Mechanisms of Disease (2011)

Epithelial cells form protective barriers that physically separate an organism from the outside world. Rather than being merely static, impregnable shields, epithelia are highly dynamic structures that can adjust their proliferation, differentiation, and death in response to intrinsic and extrinsic signals. The advantages as well as pitfalls of this flexibility are highlighted in inflammatory disorders such as inflammatory bowel diseases and psoriasis, which are characterized by a chronically dysregulated homeostasis of the epithelium. In recent years, it has become increasingly apparent that epithelial cells communicate with their surroundings through converging, integrated signaling cascades and that even minor alterations in these pathways can have dramatic pathologic consequences. In this review, we discuss how inflammatory cytokines and other signaling molecules, directly or through cross talk, regulate epithelial homeostasis in the intestine, and we highlight parallels and differences in a few other organs.
Sweetened Beverage Consumption, Incident Coronary Heart Disease, and Biomarkers of Risk in Men
Authors: Lawrence de Koning, Vasanti S. Malik, Mark D. Kellogg, Eric B. Rimm, Walter C. Willett, Frank B. Hu
Journal: Circulation (2012)

Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes mellitus. Few studies have tested for a relationship with coronary heart disease (CHD) or intermediate biomarkers. The role of artificially sweetened beverages is also unclear.We performed an analysis of the Health Professionals Follow-Up Study, a prospective cohort study including 42 883 men. Associations of cumulatively averaged sugar-sweetened (eg, sodas) and artificially sweetened (eg, diet sodas) beverage intake with incident fatal and nonfatal CHD (myocardial infarction) were examined with proportional hazard models. There were 3683 CHD cases over 22 years of follow-up. Participants in the top quartile of sugar-sweetened beverage intake had a 20% higher relative risk of CHD than those in the bottom quartile (relative risk=1.20; 95% confidence interval, 1.09-1.33; P for trend <0.01) after adjustment for age, smoking, physical activity, alcohol, multivitamins, family history, diet quality, energy intake, body mass index, pre-enrollment weight change, and dieting. Artificially sweetened beverage consumption was not significantly associated with CHD (multivariate relative risk=1.02; 95% confidence interval, 0.93-1.12; P for trend=0.28). Adjustment for self-reported high cholesterol, high triglycerides, high blood pressure, and diagnosed type 2 diabetes mellitus slightly attenuated these associations. Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased plasma triglycerides, C-reactive protein, interleukin-6, and tumor necrosis factor receptors 1 and 2 and decreased high-density lipoprotein, lipoprotein(a), and leptin (P<0.02).Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids, inflammatory factors, and leptin. Artificially sweetened beverage intake was not associated with CHD risk or biomarkers.
Mechanism of NaCl and water reabsorption in the proximal convoluted tubule of rat kidney.
Authors: K H Neumann, F C Rector
Journal: Journal of Clinical Investigation (1976)

The role of chloride concentration gradients in proximal NaCl and water reabsorption was examined in superficial proximal tubules of the rat by using perfusion and collection techniques. Reabsorptive rates (Jv), chloride concentrations, and transtubular potential difference were measured during perfusion with solutions (A) simulating an ultrafiltrate of plasma; (B) similar to (A) except that 20 meq/liter bicarbonate was replaced with acetate; (C) resembling late proximal fluid (glucose, amino acid, acetate-free, low bicarbonate, and high chloride); and (D) in which glucose and amino acids were replaced with raffinose and bicarbonate was partially replaced by poorly reabsorbable anions (cyclamate,sulfate, and methyl sulfate). In tubules perfused with solutions A and B, Jv were 2.17 and 2.7 nl mm-1 min-1 and chloride concentrations were 131.5 +/- 3.1 and 135 +/- 395 meq/liter, respectively, indicating that reabsorption is qualitatively similar to free-flow conditions and that acetate adequately replaces bicarbonate. With solution C, Jv was 2.10 nl mm-1 min-1 and potential difference was +1.5 +/- 0.2 mV, indicating that the combined presence of glucose, alanine, acetate, and bicarbonate per se is not an absolute requirement. Fluid reabsorption was virtually abolished when tubules were perfused with D solutions; Jv was not significantly different from zero despite sodium and chloride concentrations similar to plasma; chloride concentration was 110.8 +/- 0.2 meq/liter and potential difference was -0.98 mV indicating that chloride was close to electrochemical equilibrium. These results suggest the importance of the chloride gradient to proximal tubule reabsorption in regions where actively reabsorbable solutes (glucose, alanine, acetate, and bicarbonate) are lacking and provide further evidence for a passive model of NaCl and water transport.
Egg-Specific IgA and IgA2 Are Associated with Sustained Unresponsiveness to Egg Following Oral Immunotherapy
Authors: Benjamin L. Wright, Michael D. Kulis, Kelly Orgel, A. Wesley Burks, Peter Dawson, Stacie M. Jones, Robert A. Wood, Scott H. Sicherer, Robert W. Lindblad, Don Stablein, Andrew H. Liu, Donald Y.M. Leung, Brian P. Vickery, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2015)
Parenteral Nutrition Does Not Improve Postoperative Recovery from Radical Cystectomy: Results of a Prospective Randomised Trial
Authors: Beat Roth, Frédéric D. Birkhäuser, Pascal Zehnder, George N. Thalmann, Mirjam Huwyler, Fiona C. Burkhard, Urs E. Studer
Journal: European Urology (2012)
Segregation is not good for patients with cystic fibrosis
Authors: Duncan Geddes
Journal: Journal of the Royal Society of Medicine (2008)

This is an intentionally polarized opinion presented as part of a debate. A pro–con debate works best by exaggerating two opposing points of view as a way of stimulating an open discussion. When, however, the same debate is written down the arguments can be taken out of context and so be misleading. The middle ground between two polarized positions can be lost, and in a supremely important area such as cross-infection this can be dangerous. This article must not, therefore, be taken as definitive but rather as a contribution to a vitally important discussion about how best to run a cystic fibrosis (CF) service.

First some definitions. Segregation for this debate means cohort segregation or the clustering of people with CF either as in- or out-patients according to the bacteria that they carry. This is not the same thing as infection control. Cohort segregation may or may not be a part of the much more complex business of infection control but can never be the whole story. A clinic could have infection control without segregation. It could do this by ensuring no contact between patients as a part of best practice infection control. Conversely, it would be possible to have segregation without infection control, if for example patients came to a Pseudomonas-only clinic but the doctors did not wash their hands. The American guidelines for infection control in CF recommend strict infection control without cohort segregation while the UK prefers a combination of both and puts great emphasis on cohort segregation.

I will present two main arguments. First, that infection control is essential, complex, many faceted and far more important than cohort segregation. Second, that cohort segregation is an illusion. It is illogical, unrealistic, ignores the complexity of CF microbiology and is occasionally harmful. Also, it can deflect attention from much more important issues of good infection control and is therefore not good for our patients.
Intake of <i>Lactobacillus reuteri</i> Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans: A Proof of Concept
Authors: Marie-Christine Simon, Klaus Strassburger, Bettina Nowotny, Hubert Kolb, Peter Nowotny, Volker Burkart, Fariba Zivehe, Jong-Hee Hwang, Peter Stehle, Giovanni Pacini, Bolette Hartmann, Jens J. Holst, Colin MacKenzie, Laure B. Bindels, Ines Martinez, Jens Walter, Birgit Henrich, Nanette C. Schloot, Michael Roden
Journal: Diabetes Care (2015)

OBJECTIVE Ingestion of probiotics can modify gut microbiota and alter insulin resistance and diabetes development in rodents. We hypothesized that daily intake of Lactobacillus reuteri increases insulin sensitivity by changing cytokine release and insulin secretion via modulation of the release of glucagon-like peptides (GLP)-1 and -2. RESEARCH DESIGN AND METHODS A prospective, double-blind, randomized trial was performed in 21 glucose-tolerant humans (11 lean: age 49 ± 7 years, BMI 23.6 ± 1.7 kg/m2; 10 obese: age 51 ± 7 years, BMI 35.5 ± 4.9 kg/m2). Participants ingested 1010 b.i.d. L. reuteri SD5865 or placebo over 4 weeks. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion, and euglycemic-hyperinsulinemic clamps with [6,6-2H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose production. Muscle and hepatic lipid contents were assessed by 1H-magnetic resonance spectroscopy, and immune status, cytokines, and endotoxin were measured with specific assays. RESULTS In glucose-tolerant volunteers, daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2 release by 76% (P &amp;lt; 0.01) and 43% (P &amp;lt; 0.01), respectively, compared with placebo, along with 49% higher insulin (P &amp;lt; 0.05) and 55% higher C-peptide secretion (P &amp;lt; 0.05). However, the intervention did not alter peripheral and hepatic insulin sensitivity, body mass, ectopic fat content, or circulating cytokines. CONCLUSIONS Enrichment of gut microbiota with L. reuteri increases insulin secretion, possibly due to augmented incretin release, but does not directly affect insulin sensitivity or body fat distribution. This suggests that oral ingestion of one specific strain may serve as a novel therapeutic approach to improve glucose-dependent insulin release.
Enterococci Resistant to Multiple Antimicrobial Agents, Including Vancomycin: Establishment of Endemicity in a University Medical Center
Authors: J. Glenn Morris
Journal: Annals of Internal Medicine (1995)

Objectives: To determine the distribution of and risk factors for colonization and infection with vancomycin-resistant enterococci; to evaluate the molecular epidemiology of these strains; and to assess the effect of interventions, including 1) strict adherence to infection control procedures and 2) restricted use of vancomycin. Design: Problem identification based on descriptive studies, point-prevalence surveys, and case–control studies and followed by specific interventions and evaluation of the response to these interventions. Setting: University medical center. Participants: All patients hospitalized between May 1992 and June 1994 (59 196 admissions). Main Results: 75 active infections attributed to vancomycin-resistant enterococci were identified. Thirty-one patients (41%) had bloodstream infections and 6 (8%) died. The incidence of active infection was highest in the organ transplantation unit (13.2 infections/1000 admissions). In the point-prevalence studies, vancomycin-resistant enterococci were isolated from 20% of a random sample of hospitalized patients in July, August, and September 1993 [adjusted prevalence, 16.9%]. Case-control studies showed significant associations between colonization and infection and 1) receipt of antimicrobial agents, particularly vancomycin, and 2) severity of illness. Although several small case clusters had isolates with identical banding patterns on pulsed-field gel electrophoresis, at least 45 different banding patterns were noted among medical center isolates. Interventions took place in November and December 1993. Vancomycin restriction policies resulted in a 59% decrease in intravenous vancomycin use and an 85% decrease in oral vancomycin use. Point-prevalence surveys done in April, May, and June 1994 showed a consistent 20% level of colonization with vancomycin-resistant enterococci strains (adjusted prevalence, 18.7%). No significant changes were seen in rates of vancomycin-resistant enterococci infection. Conclusions: Vancomycin-resistant enterococci are an important cause of illness and death in the study institution, particularly among organ transplant recipients and other seriously ill persons; they have also become a common intestinal colonizer among hospitalized patients. The diversity of isolates (based on molecular typing studies) suggests that resistant organisms have been introduced from multiple sources. Interventions that effectively lower the overall level of colonization with vancomycin-resistant enterococci must still be identified.
Nonuniform vasomotor responses of the coronary microcirculation to serotonin and vasopressin.
Authors: K G Lamping, H Kanatsuka, C L Eastham, W M Chilian, M L Marcus
Journal: Circulation Research (1989)

Large-conduit coronary arteries respond to vasoactive stimuli differently than smaller coronary arterioles, but the quantitative effects of many vasoactive stimuli at various levels of the microvasculature remain unknown. To determine the site of constriction or dilation to serotonin and vasopressin in the coronary microcirculation, we studied microvascular responses in the left ventricle of anesthetized cats (n = 36). To compensate for motion due to contraction of the heart, the epicardium was visualized with stroboscopic epi-illumination controlled by a computer to flash once per cardiac cycle in mid-diastole, making the vessels appear stationary. Serotonin (16 micrograms/kg/min) or vasopressin (0.5 units/min) was infused into the left atrium while maintaining aortic pressure constant with a snare on the descending aorta or inferior vena cava. Myocardial blood flow was measured with radioactive microspheres. During infusion of serotonin, aortic pressure and heart rate did not change, but myocardial perfusion increased 90 +/- 38% (mean +/- SEM) from a control value of 159 +/- 27 ml/min.100 g. Arteries and arterioles larger than 90 microns constricted in response to serotonin (control 159 +/- 12 microns; percent change -18 +/- 3; range -41 to 10%) while arterioles less than 90 microns dilated to serotonin (control 54 +/- 7 microns; percent change 22 +/- 9; range -10 to 62%). During infusion of vasopressin, aortic pressure and heart rate did not change, and myocardial perfusion decreased 16 +/- 7% (control, 147 +/- 18 ml/min.100 g).(ABSTRACT TRUNCATED AT 250 WORDS)
A population survey of respiratory symptoms in the elderly
Authors: L Dow, D Coggon, C Osmond, ST Holgate
Journal: European Respiratory Journal (1991)

Reversible airways obstruction is not uncommon in the elderly, but may be overlooked because of the high prevalence of other disorders with a similar presentation. In a search for patterns of symptoms which might predict treatable airways obstruction, we carried out a survey of men and women aged 65 yrs and over. Postal questionnaires were completed by 2,161 subjects selected at random from the lists of three general practices. Almost 60% of the sample complained of one or more respiratory symptoms. Smoking was a more important risk factor than age, sex or social class, and was associated particularly with wheeze, morning phlegm and chest tightness on waking. Several groups of symptoms tended to cluster in the same individuals. The two most closely related were chest tightness and breathlessness in response to animals, dust and feathers. Responses to irritants tended to cluster according to the symptom produced (cough, breathlessness or wheeze) rather than the provoking stimulus (smoke, cold air, household chemicals or traffic fumes). There was no evidence for the existence of the "bronchial irritability syndrome" which has been linked with asthma in younger adults. The relationship of symptoms to respiratory function and bronchial reactivity will be reported in a further publication.
Targeted Inhibition of Mammalian Target of Rapamycin Signaling Inhibits Tumorigenesis of Colorectal Cancer
Authors: Pat Gulhati, Qingsong Cai, Jing Li, Jianyu Liu, Piotr G. Rychahou, Suimin Qiu, Eun Y. Lee, Scott R. Silva, Kanika A. Bowen, Tianyan Gao, B. Mark Evers
Journal: Clinical Cancer Research (2009)

The mammalian target of rapamycin (mTOR) kinase acts downstream of phosphoinositide 3-kinase/Akt to regulate cellular growth, metabolism, and cytoskeleton. Because approximately 60% of sporadic colorectal cancers (CRC) exhibit high levels of activated Akt, we determined whether downstream mTOR signaling pathway components are overexpressed and activated in CRCs.HCT116, KM20, Caco-2, and SW480 human CRC cells were used to determine the effects of pharmacologic (using rapamycin) or genetic (using RNAi) blockade of mTOR signaling on cell proliferation, apoptosis, cell cycle progression, and subcutaneous growth in vivo.We show that the mTOR complex proteins mTOR, Raptor, and Rictor are overexpressed in CRC. Treatment with rapamycin significantly decreased proliferation of certain CRC cell lines (rapamycin sensitive), whereas other cell lines were resistant to its effects (rapamycin resistant). Transient siRNA-mediated knockdown of the mTORC2 protein, Rictor, significantly decreased proliferation of both rapamycin-sensitive and rapamycin-resistant CRC cells. Stable shRNA-mediated knockdown of both mTORC1 and mTORC2 decreased proliferation, increased apoptosis, and attenuated cell cycle progression in rapamycin-sensitive CRCs. Moreover, stable knockdown of both mTORC1 and mTORC2 decreased proliferation and attenuated cell cycle progression, whereas only mTORC2 knockdown increased apoptosis in rapamycin-resistant CRCs. Finally, knockdown of both mTORC1 and mTORC2 inhibited growth of rapamycin-sensitive and rapamycin-resistant CRCs in vivo when implanted as tumor xenografts.Targeted inhibition of the mTORC2 protein, Rictor, leads to growth inhibition and induces apoptosis in both rapamycin-sensitive and rapamycin-resistant CRCs, suggesting that selective targeting of mTORC2 may represent a novel therapeutic strategy for treatment of CRC.
Glucuronidation Genotypes and Nicotine Metabolic Phenotypes: Importance of Functional UGT2B10 and UGT2B17 Polymorphisms
Authors: Gang Chen, Nino E. Giambrone, Douglas F. Dluzen, Joshua E. Muscat, Arthur Berg, Carla J. Gallagher, Philip Lazarus
Journal: Cancer Research (2010)

Abstract Glucuronidation is an important pathway in the metabolism of nicotine, with previous studies suggesting that ∼22% of urinary nicotine metabolites are in the form of glucuronidated compounds. Recent in vitro studies have suggested that the UDP-glucuronosyltransferases (UGT) 2B10 and 2B17 play major roles in nicotine glucuronidation with polymorphisms in both enzymes shown to significantly alter the levels of nicotine-glucuronide, cotinine-glucuronide, and trans-3′-hydroxycotinine (3HC)–glucuronide in human liver microsomes in vitro. In the present study, the relationship between the levels of urinary nicotine metabolites and functional polymorphisms in UGTs 2B10 and 2B17 was analyzed in urine specimens from 104 Caucasian smokers. Based on their percentage of total urinary nicotine metabolites, the levels of nicotine-glucuronide and cotinine-glucuronide were 42% (P &amp;lt; 0.0005) and 48% (P &amp;lt; 0.0001), respectively, lower in the urine from smokers exhibiting the UGT2B10 (*1/*2) genotype and 95% (P &amp;lt; 0.05) and 98% (P &amp;lt; 0.05), respectively, lower in the urine from smokers with the UGT2B10 (*2/*2) genotype compared with the urinary levels in smokers having the wild-type UGT2B10 (*1/*1) genotype. The level of 3HC-glucuronide was 42% (P &amp;lt; 0.001) lower in the urine from smokers exhibiting the homozygous UGT2B17 (*2/*2) deletion genotype compared with the levels in urine from wild-type UGT2B17 subjects. These data suggest that UGTs 2B10 and 2B17 play important roles in the glucuronidation of nicotine, cotinine, and 3HC and suggest that the UGT2B10 codon 67 SNP and the UGT2B17 gene deletion significantly reduce overall glucuronidation rates of nicotine and its major metabolites in smokers. Cancer Res; 70(19); 7543–52. ©2010 AACR.