tbuckley/cabot-search huggingface dataset:
Renal dysfunction in cirrhosis is not just a vasomotor nephropathy
Authors: Danielle Adebayo, Vincenzo Morabito, Andrew Davenport, Rajiv Jalan
Journal: Kidney International (2014)

The short-term mortality of cirrhotic patients who develop renal dysfunction remains unacceptably high, and as such the treatment of this condition is an unmet need. Although features of kidney injury are well recognized in these patients, the pathophysiology is complex and not completely understood. Improved understanding of the pathophysiological mechanisms involved in renal dysfunction occurring on a background of cirrhosis is key to developing effective treatment strategies to improve survival. Renal dysfunction due to hepatorenal syndrome (HRS) is characteristic of cirrhosis. Our current understanding is that HRS is functional in nature and occurs as a consequence of hemodynamic changes associated with portal hypertension. However, there is evidence in the literature suggesting that, histologically, the kidneys are not always normal in the vast majority of patients who present with renal dysfunction on the background of cirrhosis. Furthermore, there is emerging data implicating nonvasomotor mechanisms in the pathophysiology of renal dysfunction in cirrhosis. This mini-review aims to present the evidence suggesting that factors other than hemodynamic dysregulation have an important role in the development of this major complication for patients with progressive cirrhosis.
Deficiency of factor B of the complement system in sickle cell anaemia.
Authors: W A Wilson, G R Hughes, P J Lachmann
Journal: BMJ (1976)

Factors B and D as well as the total activity of the alternative pathway of complement activation were measured using a functional assay in sera from 29 patients with sickle cell anaemia and 18 normal controls. Total alternative pathway activity was reduced in the patients compared with controls. In patients with abnormally low total alternative pathway activity factor D levels were normal, whereas factor B levels were significantly depressed to a mean level of about half of normal. Regression analysis in patients also showed a significant relation between total alternative pathway activity and factor B levels. A deficiency of factor B is the likely cause of the defect in the complement system in patients with sickle cell anaemia. Such a defect may contribute to the excessive proneness of such patients to severe infection.
Intact Antibody Response to Pneumococcal Capsular Polysaccharides in Uremia and Diabetes
Authors: Eli A. Friedman
Journal: JAMA (1980)

To test their immune responsiveness to pneumococcal polysaccharide antigens, eight azotemic patients, ten dialysis patients, and five insulin-dependent diabetics were vaccinated with a 14-valent vaccine. When compared with nonazotemic, nondiabetic control subjects, both diabetics and uremic patients responded with normal antibody titers to each antigen type. Therefore, we are advising immunization with commercially available vaccine in our patients with diabetes, renal failure, or both, although long-term efficacy has yet to be proved.
The Effect of Natural Allergen Exposure on the Maximal Response Plateau to Adenosine 5′-monophosphate and on Exhaled Nitric Oxide of Alveolar and Bronchial Origin in Subjects with Pollen Allergy
Authors: L. Prieto, V. Lopez, C. Perez-Frances, D. Barato, A. Lucas
Journal: Journal of Allergy and Clinical Immunology (2010)
The Pelvic Examination: A View from the Other End of the Table
Authors: JONI MAGEE
Journal: Annals of Internal Medicine (1975)

Lying on the examining table, feet in stirrups, confronting the examiner with the most personal parts of your anatomy, gives you plenty of time to think. Because I also perform pelvic examinations, what I thought about was what could be done to make me like them better. During the years certain parts of the procedure stood out as crucial. Speculum insertion is usually the most traumatic event in the examination. A detailed explanation of the sensations experienced and suggestions for alleviating some of them are presented. Other aspects of the doctor-patient relation during the pelvic examination are explored and suggestions for improving patients' perceptions of them are offered.
T3 The Effect Of Electronic Cigarette Exposure On Innate Immune Cells
Authors: A. Higham, N. Rattray, J. Dewhurst, D. Singh
Journal: Thorax (2014)

<h3>Introduction</h3> Are electronic cigarettes (e-cigs) safe? The long-term effects of e-cigs are unknown. E-cigs contain a variety of substances that may be harmful to the lungs. We hypothesised that e-cigs have the potential to cause pulmonary inflammation. We have investigated the effects of e-cigs on human innate immune cells <i>in vitro</i>. <h3>Methods</h3> Blood neutrophils from six healthy non-smokers were exposed to e-cig vapour extract (ECVE) for 6 hr. MMP-9 and CXCL8 release were measured by ELISA and MMP-9 activity was measured by zymography. p38 MAPK activation was also measured, along with neutrophil shape change and CD11b and CD66b expression by flow cytometry. Finally, we measured CXCL8 release from alveolar macrophages isolated from resected lung tissue from three ex-tobacco smokers exposed to ECVE for 24 hr. <h3>Results</h3> Exposure of neutrophils to ECVE increased MMP-9 and CXCL8 release with the maximal effect observed at an optical density (OD) of 0.003 (Table 1). This was observed along with an increase in MMP-9 gelatinase activity and increased p38 MAPK activation. Furthermore, neutrophil shape change, and dual CD11b and CD66b expression increased in response to ECVE treatment compared to untreated cells. Following a similar trend, 0.003 (OD) ECVE caused an increase in CXCL8 release from alveolar macrophages. <h3>Discussion</h3> We have shown that e-cig exposure causes an inflammatory response from neutrophils and macrophages. The effects discussed here are similar to those caused by tobacco cigarettes. Based on these findings, the use of e-cigs may pose a risk to public health.
Diagnostic Precursors to Bipolar Disorder in Offspring of Parents With Bipolar Disorder: A Longitudinal Study
Authors: David Axelson, Benjamin Goldstein, Tina Goldstein, Kelly Monk, Haifeng Yu, Mary Beth Hickey, Dara Sakolsky, Rasim Diler, Danella Hafeman, John Merranko, Satish Iyengar, David Brent, David Kupfer, Boris Birmaher
Journal: American Journal of Psychiatry (2015)

Objective: The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder (“high-risk offspring”). Method: High-risk offspring 6–18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean follow-up interval, 2.5 years; mean follow-up duration, 6.8 years). Results: Compared with community offspring, high-risk offspring had significantly higher rates of subthreshold mania or hypomania (13.3% compared with 1.2%), manic, mixed, or hypomanic episodes (9.2% compared with 0.8%), and major depressive episodes (32.0% compared with 14.9%). They also had higher rates of attention deficit hyperactivity disorder (30.7% compared with 18.1%), disruptive behavior disorders (27.4% compared with 15.3%), anxiety disorders (39.9% compared with 21.8%), and substance use disorders (19.9% compared with 10.1%), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% compared with 13.7%). Multivariate Cox regressions showed that in the high-risk offspring, subthreshold manic or hypomanic episodes (hazard ratio=2.29), major depressive episodes (hazard ratio=1.99), and disruptive behavior disorders (hazard ratio=2.12) were associated with subsequent manic, mixed, or hypomanic episodes. Only subthreshold manic or hypomanic episodes (hazard ratio=7.57) were associated when analyses were restricted to prospective data. Conclusions: Subthreshold manic or hypomanic episodes were a diagnostic risk factor for the development of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder and should be a target for clinical assessment and treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.
The Electrical Treatment of Ticdouloureux
Authors: W. J. Turrell
Journal: BMJ (1926)

ELIECTR[CAL TREATMENT OF TIC-DOTT8OUREU 989 (4) December 9th.-0.5 c.cm. forty-eight hours broth culture subcutaneously.Mouse died at 12 noon, November 10th.Strepto- coccus recovered in pure c-ulture from heart's blood.C.V2 was of only slight viruilence, producing no apparent ill effects when inoculated into a mouse, but being recovered forom the spleen when the animal was cliloroformed.The mice had been kept under observation for some days and dll appeared very healthy.Mouse I was inoculated subcutaneously on December 15th with 1 c.cm. sterile filtrate from a forty-eight hours broth culture of R.V2, filtered through a Berkefeld filter, and on December 18th with 0.9 c.cm. of the same filtrate.It was not very well for two days after the second inoculation.Mouse II (very much the smallest of the four) was inoculated subcutaneously on December 15th with 1 c.cm. filtrate from a Torty-eight hours broth culture of C.V2, and on December 18th with 1 c.cmh. of the same filtrate.It remained quite well after both inoculations.On December 23rd Mice I and II were inoculated with 0.5 c.cm. of a forty-eight hours broth culture of R.V2 subcutaneously, and two other normal untreated mice (III and IV) were also inocu- lated with 0.5 c.cm. of the same culture from the samie tube.Mouse III was vpry ill the following morning (December 24th) and died that night.The streptococcus was recovered in pure culture from spleen and heart's blood.Mouse IV seemed well enough on December 24th, but became ill on December 25th, and died that night.The streptococcus was recovered in pure culture from spleen and lheart's blood.
Abstract 9241: High Sugar Intake May Improve Survival and Does Not Adversely Affect Cardiac and Metabolic Dysfunction in Genetic Cardiomyopathy
Authors: Peter A Hecker, Tatiana F Galvao, Karen M O'Shea, Bethany H Brown, Reney Hendersen, Heather Riggle, Sachin A Gupte, William C Stanley
Journal: Circulation (2011)

High sugar intake increases the risk of heart disease in humans, and in some animal models of hypertension it increases oxidative stress and accelerates the development of heart failure. Recent studies suggest that glucose 6-phosphate dehydrogenase (G6PD) may be responsible for ROS generation, as it produces NADPH, which is used by NADPH oxidase to produce superoxide, while on the other hand it can facilitate the removal of reactive oxygen species (ROS) via the glutathione pathway. We hypothesized that a high sugar diet would increase flux through G6PD to increase myocardial [NADPH] and ROS production, and accelerate cardiac dysfunction and death. Cardiomyopathic TO-2 hamsters, a nonhypertensive model of genetic cardiomyopathy, were fed a either a high starch/sugar free diet or a high sugar diet (57% of energy from fructose +sucrose; n=12/group for echocardiography and biochemical analysis; n=30/cardiomyopathic group and n=10 healthy controls for survival analysis). However, after 24 weeks, the high sugar diet alleviated the decrease in ejection fraction associated with cardiomyopathy, and there was a strong trend for high sugar intake to increase survival (p=0.087)(Figure). High sugar intake increased left ventricular superoxide production, but did not affect [NADPH] or lipid peroxidation products. Cardiomyopathy resulted in metabolic abnormalities including decreased left ventricular mitochondrial oxidative enzyme activities, high circulating glucose, triglycerides and free fatty acids and decreased insulin, however the high sugar diet did not affect any of these parameters. These results indicate that despite a sugar-induced increase in superoxide production, there was no worsening of cardiac function or survival. In contrast, the high sugar diet improved systolic dysfunction and show a strong trend for prolonged survival.
Inorganic Arsenic and Basal Cell Carcinoma in Areas of Hungary, Romania, and Slovakia: A Case–Control Study
Authors: Giovanni Leonardi, Marie Vahter, Felicity Clemens, Walter Goessler, Eugen Gurzau, Kari Hemminki, Rupert Hough, Kvetoslava Koppova, Rajiv Kumar, Peter Rudnai, Simona Surdu, Tony Fletcher
Journal: Environmental Health Perspectives (2012)

Inorganic arsenic (iAs) is a potent carcinogen, but there is a lack of information about cancer risk for concentrations < 100 μg/L in drinking water.We aimed to quantify skin cancer relative risks in relation to iAs exposure < 100 μg/L and the modifying effects of iAs metabolism.The Arsenic Health Risk Assessment and Molecular Epidemiology (ASHRAM) study, a case-control study, was conducted in areas of Hungary, Romania, and Slovakia with reported presence of iAs in groundwater. Consecutively diagnosed cases of basal cell carcinoma (BCC) of the skin were histologically confirmed; controls were general surgery, orthopedic, and trauma patients who were frequency matched to cases by age, sex, and area of residence. Exposure indices were constructed based on information on iAs intake over the lifetime of participants. iAs metabolism status was classified based on urinary concentrations of methylarsonic acid (MA) and dimethylarsinic acid (DMA). Associations were estimated by multivariable logistic regression.A total of 529 cases with BCC and 540 controls were recruited for the study. BCC was positively associated with three indices of iAs exposure: peak daily iAs dose rate, cumulative iAs dose, and lifetime average water iAs concentration. The adjusted odds ratio per 10-μg/L increase in average lifetime water iAs concentration was 1.18 (95% confidence interval: 1.08, 1.28). The estimated effect of iAs on cancer was stronger in participants with urinary markers indicating incomplete metabolism of iAs: higher percentage of MA in urine or a lower percentage of DMA.We found a positive association between BCC and exposure to iAs through drinking water with concentrations < 100 μg/L.
Successful delivery of information technology in the NHS
Authors: P. Altmann, J. Michael
Journal: BMJ (2011)

Chief clinical information officers are needed to lead the information revolution

In a time of austerity it might be unpopular to suggest that every NHS organisation needs a new high level post: a chief clinical information officer (CCIO). Yet it is an idea that is gathering support and leading to action in some quarters.

A campaign was recently launched (www.ehi.co.uk/campaign/ccio) to encourage NHS organisations to appoint a CCIO. Organised by eHealth Insider, a news and information channel on healthcare information technology, with the British Computer Society and the Royal College of Physicians as partners, the campaign has attracted many supporters. Five royal colleges; NHS medical director, Bruce Keogh; health minister, Lord Howe; 27 IT firms; and numerous individual clinicians and IT professionals have endorsed it to date.

One of the drivers behind this campaign is unfortunately a negative one. Although the NHS can be proud of some of its achievements in IT, there have been too many failures, particularly in secondary care. In many cases, commercial complications and a lack of engagement with doctors and nurses, the primary users of clinical IT systems, have been cited as factors.

The need for clinical engagement and leadership were highlighted by Frank Burns in 1998.1 However, the NHS never promoted the importance of this, and ten years later the …
Myoblast morphology and organization on biochemically micro-patterned hydrogel coatings under cyclic mechanical strain
Authors: Wylie W. Ahmed, Tobias Wolfram, Alexandra M. Goldyn, Kristina Bruellhoff, Borja Aragüés Rioja, Martin Möller, Joachim P. Spatz, Taher A. Saif, Jürgen Groll, Ralf Kemkemer
Journal: Biomaterials (2009)
Abstract A94: Imatinib modulates CD4+ T cells in gastrointestinal stromal tumor (GIST).
Authors: Vinod P. Balachandran, Michael Cavnar, Shan Zeng, Zubin Bamboat, Lee Ocuin, Hebroon Obaid, Eric Sorenson, Teresa Kim, Rachel Popow, Ronald P. DeMatteo
Journal: Cancer Research (2013)

Abstract Introduction: Imatinib mesylate partially exerts its antitumor effects in GIST by inhibiting tumor production of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (Ido), thereby activating antitumor CD8+ T cells. The role of conventional CD4+ T cells (CD4+FoxP3-) in imatinib therapy is unknown. We examined the effects of imatinib on CD4+ T cells in GIST. Methods: We injected imatinib or saline intraperitoneally for one week to KitV558-/+ mice that develop spontaneous GISTs. 1-methyl-D-tryptophan (D-1MT), an Ido inhibitor was given via oral gavage. We assessed treatment response by tumor weight and immune cells by flow cytometry. Regulatory T cells (Treg) were defined as CD4+FoxP3+. Matched blood and tumor specimens from GIST patients were freshly analyzed for immune composition. Tumors were classified as untreated, sensitive, or resistant to imatinib based on radiologic assessment just before the time of surgery. Results: Imatinib increased CD4+ number, activation, and degranulation in the draining lymph node (DLN) but not the spleen of GIST mice (p&amp;lt;0.05). In the tumor, imatinib increased CD4+ number, activation, proliferation, and the intratumoral CD4+/Treg ratio (p&amp;lt;0.05). Conversely, Ido inhibition did not alter CD4+ number, activation, proliferation, or the CD4+/Treg ratio in the DLN or tumor. In untreated human GISTs (n=14), CD4+ T cells demonstrated greater activation and memory phenotype compared to autologous blood CD4+ T cells, but secreted Th2 cytokines on in vitro restimulation (p&amp;lt;0.05). Imatinib treatment altered the intratumoral CD4+/Treg ratio, with a higher ratio in sensitive tumors (n=17) compared to resistant tumors (n=12; p&amp;lt;0.05). Conclusion: In mouse GIST, imatinib activates CD4+ T cells independently of Ido and increases the intratumoral CD4+/Treg ratio, a hallmark of immunologic outcome. Similarly, imatinib sensitive human GISTs have a higher CD4+/Treg ratio than resistant tumors. Hence, CD4+ T cells may contribute to the antitumor effects of imatinib in GIST. Combination immunotherapy with imatinib and CD4+ T cell modulating agents may be a promising therapy for GIST. Citation Format: Vinod P. Balachandran, Michael Cavnar, Shan Zeng, Zubin Bamboat, Lee Ocuin, Hebroon Obaid, Eric Sorenson, Teresa Kim, Rachel Popow, Ronald P. DeMatteo. Imatinib modulates CD4+ T cells in gastrointestinal stromal tumor (GIST). [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr A94.
Covered vs. uncovered stents for transjugular intrahepatic portosystemic shunt: A randomized controlled trial
Authors: Jean Marc Perarnau, Amélie Le Gouge, Charlotte Nicolas, Louis d’Alteroche, Patrick Borentain, Faouzi Saliba, Anne Minello, Rodolphe Anty, Carine Chagneau-Derrode, Pierre Henri Bernard, Armand Abergel, Isabelle Ollivier-Hourmand, Jérome Gournay, Jean Ayoub, Christophe Gaborit, Emmanuel Rusch, Bruno Giraudeau
Journal: Journal of Hepatology (2014)
Impaired Incretin Response After a Mixed Meal Is Associated With Insulin Resistance in Nondiabetic Men
Authors: Eva Rask, Tommy Olsson, Stefan Söderberg, Owe Johnson, Jonathan Seckl, Jens Juul Holst, Bo Ahrén
Journal: Diabetes Care (2001)

OBJECTIVE—To investigate whether features of the insulin resistance syndrome are associated with altered incretin responses to food intake. RESEARCH DESIGN AND METHODS—From a population-based study, 35 men were recruited, representing a wide spectrum of insulin sensitivity and body weight. Each subject underwent a hyperinsulinemic-euglycemic clamp to determine insulin sensitivity. A mixed meal was given, and plasma levels of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured. RESULTS—Insulin resistance was associated with impaired GIP and GLP-1 responses to a mixed meal. The total area under the curve (AUC) of the GIP response after the mixed meal was associated with insulin sensitivity (r = 0.54, P &amp;lt; 0.01). There was a significant difference between the highest and the lowest tertile of insulin sensitivity (P &amp;lt; 0.05). GLP-1 levels 15 min after food intake were significantly lower in the most insulin-resistant tertile compared with the most insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated significantly with insulin sensitivity (r = 0.47, P &amp;lt; 0.01). Multiple linear regression analysis showed that insulin resistance, but not obesity, was an independent predictor of these decreased incretin responses. CONCLUSIONS—In insulin resistance, the GIP and GLP-1 responses to a mixed meal are impaired and are related to the degree of insulin resistance. Decreased incretin responsiveness may be of importance for the development of impaired glucose tolerance.
Effects of fluids on microvascular perfusion in patients with severe sepsis
Authors: Gustavo Ospina-Tascon, Ana Paula Neves, Giovanna Occhipinti, Katia Donadello, Gustavo Büchele, Davide Simion, Maria-Luisa Chierego, Tatiana Oliveira Silva, Adriana Fonseca, Jean-Louis Vincent, Daniel De Backer
Journal: Intensive Care Medicine (2010)
What to Expect From Expectorants
Authors: Irwin Ziment
Journal: JAMA (1976)

DO MEDICATIONS really help mobilize mucus from the respiratory tract? Are the traditional physicians correct when they try to get the asthmatic child to "vomit" sputum out of the lungs? Do all the numerous cough and cold mixtures have any more effect on expectoration than the glass of water used to wash the medication down? Are inhaled agents superior to those administered by mouth? These are difficult questions to answer, and reliable information is scanty—mainly because of the well-recognized difficulty in quantifying and qualifying a patient's sputum. Nevertheless, many physicians and more patients are convinced that certain favored prescriptions do have a beneficial effect on respiratory secretions. <h3>Traditional and Modern Expectorants</h3> The various American formularies and pharmacopeias are relatively reluctant to praise the traditional expectorants, but an English drug encyclopedia, Martindale's<i>Extra Pharmacopoeia</i>, lists a surprisingly large range of such medications that are undoubtedly foisted by British physicians on their
910-22 Mitral Regurgitation (not Restenosis) is the Most Frequent Indication for Valve Replacement After Balloon Mitral Valvotomy
Authors: Ted Feldman, John D. Carroll, Howard C. Herrmann, Larry S. Dean, David R. Holmes, Donald A. Rothbaum, Gerald Dorros, Igor F. Palacios, David T. Kawanishi, Gregory S. Pavlides
Journal: Journal of the American College of Cardiology (1995)
Facilitation of NMDAR-Independent LTP and Spatial Learning in Mutant Mice Lacking Ryanodine Receptor Type 3
Authors: Akira Futatsugi, Kunio Kato, Hiroo Ogura, Sheng-Tian Li, Eiichiro Nagata, Goro Kuwajima, Kortaro Tanaka, Shigeyoshi Itohara, Katsuhiko Mikoshiba
Journal: Neuron (1999)