tbuckley/cabot-search huggingface dataset:
Clinical Results From Transplanting Incompatible Live Kidney Donor/Recipient Pairs Using Kidney Paired Donation
Authors: Robert A. Montgomery, Andrea A. Zachary, Lloyd E. Ratner, Dorry L. Segev, Janet M. Hiller, Julie Houp, Mathew Cooper, Louis Kavoussi, Thomas Jarrett, James Burdick, Warren R. Maley, J. Keith Melancon, Tomasz Kozlowski, Christopher E. Simpkins, Melissa Phillips, Amol Desai, Vanessa Collins, Brigitte Reeb, Edward Kraus, Hamid Rabb, Mary S. Leffell, Daniel S. Warren
Journal: JAMA (2005)

First proposed 2 decades ago, live kidney paired donation (KPD) was considered a promising new approach to addressing the shortage of organs for transplantation. Ethical, administrative, and logistical barriers initially proved formidable and prevented the implementation of KPD programs in the United States.To determine the feasibility and effectiveness of KPD for the management of patients with incompatible donors.Prospective series of paired donations matched and transplanted from a pool of blood type or crossmatch incompatible donors and recipients with end-stage renal disease (6 conventional and 4 unconventional KPD transplants) at a US tertiary referral center (between June 2001 and November 2004) with expertise in performing transplants in patients with high immunologic risk.Kidney paired donation and live donor renal transplantation.Patient survival, graft survival, serum creatinine levels, rejection episodes.A total of 22 patients received transplants through 10 paired donations including 2 triple exchanges at Johns Hopkins Hospital. At a median follow-up of 13 months (range, 1-42 months), the patient survival rate was 100% and the graft survival rate was 95.5%. Twenty-one of the 22 patients have functioning grafts with a median 6-month serum creatinine level of 1.2 mg/dL (range, 0.8-1.8 mg/dL) (106.1 micromol/L [range, 70.7-159.1 micromol/L]). There were no instances of antibody-mediated rejection despite the inclusion of 5 patients who were highly sensitized to HLA antigens due to previous exposure to foreign tissue. Four patients developed acute cellular rejection (18%).This series of patients who received transplants from a single-center KPD pool provides evidence that recipients with incompatible live donors, even those with rare blood type combinations or high degrees of HLA antigen sensitization, can receive transplants through KPD with graft survival rates that appear to be equivalent to directed, compatible live donor transplants. If these results can be generalized, broader availability of KPD to the estimated 6000 patients with incompatible donors could result in a large expansion of the donor pool.
EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS
Authors: Roger M. Des Prez
Journal: The Journal of Experimental Medicine (1964)

The platelet injury produced by bacterial endotoxin and thrombin have been compared in studies utilizing citrated rabbit platelet-rich plasma. Endotoxin-induced platelet injury is characterized by a lag period, is progressive, and does not produce gross clot formation. Thrombin-induced platelet injury is immediate, non-progressive, and is associated with clot formation. The quantity of thrombin required to produce clot formation in this citrated system is less than that required to produce release of platelet 5-hydroxytryptamine. The endotoxin-induced platelet injury required extremely large quantities of heparin for inhibition. The platelet injury induced by thrombin can be inhibited by small quantities of heparin. It is concluded that the injurious effects of endotoxin on platelets is mediated through some mechanism other than thrombin formation.
How to Define Prehypertension in Diabetes/Metabolic Syndrome
Authors: Avshalom Leibowitz, Ehud Grossman
Journal: Diabetes Care (2009)

Hypertension is a powerful risk factor for cardiovascular (CV) morbidity and mortality. The coexistence of hypertension and type 2 diabetes is devastating to the CV system (1). Lowering blood pressure (BP) is especially beneficial in diabetic patients, and therefore the goal BP in these patients is <130/80 mmHg rather than 140/90 mmHg, which is the goal in the general population (2,3). The Joint National Committee (JNC) VII introduced the term “prehypertension,” which is defined as BP levels of 120–139 mmHg for systolic and 80–89 mmHg for diastolic BP, respectively (2). Because the goal BP in diabetic patients and in those with metabolic syndrome is <130/80 mmHg, the question arises as to what the definition of prehypertension should be in these patients. The present review analyzes the available data to determine how to define prehypertension in diabetes/metabolic syndrome.

Despite the advances in CV medicine over the past decades, cardiovascular disease (CVD) remains the major cause of mortality and morbidity in the western world. A similar tendency has been observed over recent years in the developing world as well, where the prevalence of CVD is consistently on the increase. Although multiple factors are responsible for these phenomena, the recent rise in prevalence of type 2 diabetes is significant.

Up to two-thirds of all deaths in diabetic patients are due to a CV event. The high CVD risk of diabetic patients was shown in several studies. The San Antonio Heart Study demonstrated that type 2 diabetes increased CV mortality by about threefold in men (relative risk [RR] 3.2 [95% CI 1.4–7.1]) and by approximately eightfold in women (RR 8.5 [2.8–25.2]) (4). Data from the Framingham longitudinal study showed that type 2 diabetes increases the risk for developing congestive heart failure (CHF) by 1.8-fold in men and 3.7-fold in women (5). Because …
Hypothermia in Hypoglycemia
Authors: Barry S. Strauch
Journal: JAMA (1969)

Body temperature was investigated in 15 consecutive patients with hypoglycemia and in 20 patients with coma or stupor of diverse etiology. Hypothermia, defined as a rectal temperature of 96 F (35.6 C) or less, was observed in eight instances among the hypoglycemic group (53%) and in only one of the control subjects, a highly significant difference (P &lt; 0.01). Hypothermia was found in all five hypoglycemic patients examined between 5 AM and noon.
Small Molecules, Big Players: the National Cancer Institute's Initiative for Chemical Genetics
Authors: Nicola Tolliday, Paul A. Clemons, Paul Ferraiolo, Angela N. Koehler, Timothy A. Lewis, Xiaohua Li, Stuart L. Schreiber, Daniela S. Gerhard, Scott Eliasof
Journal: Cancer Research (2006)

Abstract In 2002, the National Cancer Institute created the Initiative for Chemical Genetics (ICG), to enable public research using small molecules to accelerate the discovery of cancer-relevant small-molecule probes. The ICG is a public-access research facility consisting of a tightly integrated team of synthetic and analytical chemists, assay developers, high-throughput screening and automation engineers, computational scientists, and software developers. The ICG seeks to facilitate the cross-fertilization of synthetic chemistry and cancer biology by creating a research environment in which new scientific collaborations are possible. To date, the ICG has interacted with 76 biology laboratories from 39 institutions and more than a dozen organic synthetic chemistry laboratories around the country and in Canada. All chemistry and screening data are deposited into the ChemBank web site (http://chembank.broad.harvard.edu/) and are available to the entire research community within a year of generation. ChemBank is both a data repository and a data analysis environment, facilitating the exploration of chemical and biological information across many different assays and small molecules. This report outlines how the ICG functions, how researchers can take advantage of its screening, chemistry and informatic capabilities, and provides a brief summary of some of the many important research findings. (Cancer Res 2006; 66(18): 8935-42)
Bilirubin. Edited by K. P. M. Heirwegh and S. P. Brown. Volume I. Chemistry. 158 pp. $48.00 and Volume II. Metabolism. 226 pp. $48.00. Boca Raton, Florida: CRC Press, 1982.
Authors: John Gollan, Antony Mcdonagh
Journal: Hepatology (1984)
G Protein–Coupled Receptor Oligomerization Revisited: Functional and Pharmacological Perspectives
Authors: Sergi Ferré, Vicent Casadó, Lakshmi A. Devi, Marta Filizola, Ralf Jockers, Martin J. Lohse, Graeme Milligan, Jean-Philippe Pin, Xavier Guitart
Journal: Pharmacological Reviews (2014)

Most evidence indicates that, as for family C G protein–coupled receptors (GPCRs), family A GPCRs form homo- and heteromers. Homodimers seem to be a predominant species, with potential dynamic formation of higher-order oligomers, particularly tetramers. Although monomeric GPCRs can activate G proteins, the pentameric structure constituted by one GPCR homodimer and one heterotrimeric G protein may provide a main functional unit, and oligomeric entities can be viewed as multiples of dimers. It still needs to be resolved if GPCR heteromers are preferentially heterodimers or if they are mostly constituted by heteromers of homodimers. Allosteric mechanisms determine a multiplicity of possible unique pharmacological properties of GPCR homomers and heteromers. Some general mechanisms seem to apply, particularly at the level of ligand-binding properties. In the frame of the dimer-cooperativity model, the two-state dimer model provides the most practical method to analyze ligand–GPCR interactions when considering receptor homomers. In addition to ligand-binding properties, unique properties for each GPCR oligomer emerge in relation to different intrinsic efficacy of ligands for different signaling pathways (functional selectivity). This gives a rationale for the use of GPCR oligomers, and particularly heteromers, as novel targets for drug development. Herein, we review the functional and pharmacological properties of GPCR oligomers and provide some guidelines for the application of discrete direct screening and high-throughput screening approaches to the discovery of receptor-heteromer selective compounds.
Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas
Authors: Yasuo Horie, Akira Suzuki, Ei Kataoka, Takehiko Sasaki, Koichi Hamada, Junko Sasaki, Katsunori Mizuno, Go Hasegawa, Hiroyuki Kishimoto, Masahiro Iizuka, Makoto Naito, Katsuhiko Enomoto, Sumio Watanabe, Tak Wah Mak, Toru Nakano
Journal: Journal of Clinical Investigation (2004)

PTEN is a tumor suppressor gene mutated in many human cancers, and its expression is reduced or absent in almost half of hepatoma patients. We used the Cre-loxP system to generate a hepatocyte-specific null mutation of Pten in mice (AlbCrePtenflox/flox mice). AlbCrePtenflox/flox mice showed massive hepatomegaly and steatohepatitis with triglyceride accumulation, a phenotype similar to human nonalcoholic steatohepatitis. Adipocyte-specific genes were induced in mutant hepatocytes, implying adipogenic-like transformation of these cells. Genes involved in lipogenesis and β-oxidation were also induced, possibly as a result of elevated levels of the transactivating factors PPARγ and SREBP1c. Importantly, the loss of Pten function in the liver led to tumorigenesis, with 47% of AlbCrePtenflox/flox livers developing liver cell adenomas by 44 weeks of age. By 74–78 weeks of age, 100% of AlbCrePtenflox/flox livers showed adenomas and 66% had hepatocellular carcinomas. AlbCrePtenflox/flox mice also showed insulin hypersensitivity. In vitro, AlbCrePtenflox/flox hepatocytes were hyperproliferative and showed increased hyperoxidation with abnormal activation of protein kinase B and MAPK. Pten is thus an important regulator of lipogenesis, glucose metabolism, hepatocyte homeostasis, and tumorigenesis in the liver.
Quality of Life: It’s Never Too Late
Authors: Christopher B. Steer, Gavin M. Marx, Eleni Galani, Peter G. Harper, David Khayat
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.13.2915 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12089218 Quality of Life: It's Never Too Late Christopher B. SteerxChristopher B. SteerSearch for articles by this author , Gavin M. MarxxGavin M. MarxSearch for articles by this author , Eleni GalanixEleni GalaniSearch for articles by this author , Peter G. HarperxPeter G. HarperSearch for articles by this author David KhayatxDavid KhayatSearch for articles by this author Show More Guy's Hospital, London, United KingdomSalpetriere Hospital, Paris, France https://doi.org/10.1200/JCO.2002.20.13.2915 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Coronal or Swinging Eyelid Decompression for Patients with Disfiguring Proptosis in Graves’ Orbitopathy?
Authors: Inna V. Sasim, Mieke E.L. de Graaf, Tos T.J.M. Berendschot, Rachel Kalmann, Chantal van Isterdael, Maarten P. Mourits
Journal: Ophthalmology (2005)
GnRH agonist for triggering final oocyte maturation in the GnRH antagonist ovarian hyperstimulation protocol: a systematic review and meta-analysis
Authors: G. Griesinger, K. Diedrich, P. Devroey, E.M. Kolibianakis
Journal: Human Reproduction Update (2005)

Triggering final oocyte maturation with GnRH agonist during ovarian stimulation is feasible when inhibition of premature LH surge is performed with GnRH antagonists, and we aimed to systematically collate evidence on the clinical efficacy of GnRH agonist triggering in patients undergoing assisted reproduction in GnRH antagonist protocols. Twenty-three publications were identified by a comprehensive literature search that included PubMed, Embase and the Cochrane Library. Three publications out of 23 fulfilled the inclusion criteria for meta-analysis, which were (i) prospective, randomized controlled study design; (ii) stimulation with gonadotropins for induction of multifollicular development; (iii) suppression of endogenous LH by a GnRH antagonist; (iv) triggering of final oocyte maturation with GnRH agonist; (v) control group randomized to receive HCG for final oocyte maturation and (vi) any means of luteal phase support other than HCG. The participants were normoovulatory women undergoing IVF. The outcomes assessed were clinical pregnancy per randomized patient; number of oocytes retrieved; proportion of metaphase II oocytes; fertilization rate; embryo quality score; first trimester abortion rate; ovarian hyperstimulation syndrome (OHSS) incidence. Results are presented as combined standardized differences of the mean and combined odds ratios, as appropriate, with 95% confidence intervals. No significant difference was found for the number of oocytes retrieved (–0.94, –0.33–0.14), proportion of metaphase II oocytes (–0.03, –0.58–0.52), fertilization rate (0.15, –0.09–0.38) or embryo quality score (0.05, –0.18–0.29). No OHSS occurred in two of the studies, whereas in one study OHSS incidence was not reported. Thus from the available data, no conclusion can be drawn as regards OHSS incidence after GnRH agonist triggering. In comparison to HCG, GnRH agonist administration is associated with a significantly reduced likelihood of achieving a clinical pregnancy (0.21, 0.05–0.84; P = 0.03). The odds of first trimester pregnancy loss is increased after GnRH agonist triggering; however, the confidence interval crosses unity (11.51, 0.95–138.98; P = 0.05). In conclusion, the use of GnRH agonist to trigger final oocyte maturation in IVF, where inhibition of premature LH surge is achieved with GnRH antagonists, yields a number of oocytes capable to undergo fertilization and subsequent embryonic cleavage, which is comparable to that achieved with HCG. However, the likelihood of an ongoing clinical pregnancy after GnRH agonist triggering is significantly lower as compared to standard HCG treatment.
Scotland produces plan to tackle binge drinking
Authors: B. Christie
Journal: BMJ (2002)

An action plan has been drawn up to tackle Scotland's culture of binge drinking, culture which is being blamed for damaging the country's future.

Alcohol problems are estimated to cost Scotland £1bn ($1.4bn; €1.6bn) a year through reduced productivity and the costs of, crime, accidentsdamage to property, and health service costsinjury and illness. The latest figures show that one in three men in Scotland and one in seven women in Scotland are exceeding recommended drinking levels.

Most worrying is the increasing incidence use of alcohol use among the young people—with …
Ileo-caecal tuberculosis
Authors: J. S. Howell, P. J. Knapton
Journal: Gut (1964)

EDITORIAL SYNOPSIS Seven patients with proven ileo-caecal tuberculosis and six others in whom the presumptive evidence of intestinal tuberculosis was very strong were admitted to the United Birmingham Hospitals in the period 1951-62.The features of the condition are described, and the difficulties of diagnosis, both clinical and pathological, are discussed.Any lesion of the bowel showing follicular lesions with giant cells should be carefully searched for tubercle bacilli.Tuberculous ulceration of the intestine has been recognized from antiquity as a serious complication of advanced pulmonary tuberculosis.In India, Ukil (1942) found that of 1,000 cases of intestinal tuberculosis 95 % were secondary to the pulmonary disease.In western countries in recent years this form of intestinal tuberculosis has become uncommon, probably due to the more effective control of tuberculosis, and Mitchell and Bristol (1954) found intestinal complications in comparatively few patients with pulmonary tuberculosis.Ileo-caecal tuberculosis without apparent lung disease was frequently diagnosed in the earlier part of this century but the diagnosis has been made less often since Crohn, Ginsburg, and Oppenheimer (1932) described the entity of regional ileitis.Both conditions involve the region of the terminal ileum and are grossly, and sometimes microscopically,
Air Pollution, Aeroallergens, and Emergency Room Visits for Acute Respiratory Diseases and Gastroenteric Disorders among Young Children in Six Italian Cities
Authors: Flavia Orazzo, Luigi Nespoli, Kazuhiko Ito, Davide Tassinari, Daniela Giardina, Maurizio Funis, Alessandra Cecchi, Chiara Trapani, Gisella Forgeschi, Massimo Vignini, Luana Nosetti, Sabrina Pigna, Antonella Zanobetti
Journal: Environmental Health Perspectives (2009)

Past studies reported evidence of associations between air pollution and respiratory symptoms and morbidity for children. Few studies examined associations between air pollution and emergency room (ER) visits for wheezing, and even fewer for gastroenteric illness. We conducted a multicity analysis of the relationship between air pollution and ER visits for wheezing and gastroenteric disorder in children 0-2 years of age.We obtained ER visit records for wheezing and gastroenteric disorder from six Italian cities. A city-specific case-crossover analysis was applied to estimate effects of particulate matter (PM), nitrogen dioxide, sulfur dioxide, ozone, and carbon monoxide, adjusting for immediate and delayed effects of temperature. Lagged effects of air pollutants up to 6 prior days were examined. The city-specific results were combined using a random-effect meta-analysis.CO and SO(2) were most strongly associated with wheezing, with a 2.7% increase [95% confidence interval (CI), 0.5-4.9] for a 1.04-microg/m(3) increase in 7-day average CO and a 3.4% (95% CI, 1.5-5.3) increase for an 8.0-microg/m(3) increase in SO(2). Positive associations were also found for PM with aerodynamic diameter < or = 10 microg and NO(2). We found a significant association between the 3-day moving average CO and gastroenteric disorders [3.8% increase (95% CI, 1.0-6.8)]. When data were stratified by season, the associations were stronger in summer for wheezing and in winter for gastroenteric disorders.Air pollution is associated with triggering of wheezing and gastroenteric disorders in children 0-2 years of age; more work is needed to understand the mechanisms to help prevent wheezing in children.
FURTHER NOTES ON THE FILTRATION OF THE VIRUS OF VACCINIA
Authors: Hugh K. Ward
Journal: The Journal of Experimental Medicine (1929)

1. A very active filtrate can be obtained from vaccinia lesions by grinding up the fresh tissue with glass fragments, emulsifying in hormone broth, centrifuging the emulsion and filtering the supernatant fluid through a Berkefeld V filter. 2. The sterile filtrate so obtained has been shown by comparative titration on rabbits to have about one-sixteenth of the activity of the non-sterile emulsion used in human vaccination. 3. Centrifugation of such a filtrate shows a partial concentration of the virus in the lowermost layer. 4. The virus survives for a long time, if the filtrate is kept near the freezing point, and probably will survive indefinitely if kept frozen. The addition of glycerine is not necessary.
Single maintenance and reliever therapy (SMART) of asthma: a critical appraisal
Authors: K. R. Chapman, N. C. Barnes, A. P. Greening, P. W. Jones, S. Pedersen
Journal: Thorax (2010)

The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting β agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6–12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7–10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy.
Sexual Dysfunctions in Women
Authors: Cindy M. Meston, Andrea Bradford
Journal: Annual Review of Clinical Psychology (2007)

In this article, we summarize the definition, etiology, assessment, and treatment of sexual dysfunctions in women. Although the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV-TR) is our guiding framework for classifying and defining women's sexual dysfunctions, we draw special attention to recent discussion in the literature criticizing the DSM-IV-TR diagnostic criteria and their underlying assumptions. Our review of clinical research on sexual dysfunction summarizes psychosocial and biomedical management approaches, with a critical examination of the empirical support for commonly prescribed therapies and limitations of recent clinical trials.