tbuckley/cabot-search huggingface dataset:
Hepatocyte-specific deletion of farnesoid X receptor delays but does not inhibit liver regeneration after partial hepatectomy in mice
Authors: Prachi Borude, Genea Edwards, Chad Walesky, Feng Li, Xiaochao Ma, Bo Kong, Grace L. Guo, Udayan Apte
Journal: Hepatology (2012)

Farnesoid X receptor (FXR), the primary bile acid-sensing nuclear receptor, also plays a role in the stimulation of liver regeneration. Whole body deletion of FXR results in significant inhibition of liver regeneration after partial hepatectomy (PHX). FXR is expressed in the liver and intestines, and recent reports indicate that FXR regulates a distinct set of genes in a tissue-specific manner. These data raise a question about the relative contribution of hepatic and intestinal FXR in the regulation of liver regeneration. We studied liver regeneration after PHX in hepatocyte-specific FXR knockout (hepFXR-KO) mice over a time course of 0-14 days. Whereas the overall kinetics of liver regrowth in hepFXR-KO mice was unaffected, a delay in peak hepatocyte proliferation from day 2 to day 3 after PHX was observed in hepFXR-KO mice compared with Cre(-) control mice. Real-time polymerase chain reaction, western blot and co-immunoprecipitation studies revealed decreased cyclin D1 expression and decreased association of cyclin D1 with CDK4 in hepFXR-KO mice after PHX, correlating with decreased phosphorylation of the Rb protein and delayed cell proliferation in the hepFXR-KO livers. The hepFXR-KO mice also exhibited delay in acute hepatic fat accumulation following PHX, which is associated with regulation of cell cycle. Further, a significant delay in hepatocyte growth factor-initiated signaling, including the AKT, c-myc, and extracellular signal-regulated kinase 1/2 pathways, was observed in hepFXR-KO mice. Ultraperformance liquid chromatography/mass spectroscopy analysis of hepatic bile acids indicated no difference in levels of bile acids in hepFXR-KO and control mice.Deletion of hepatic FXR did not completely inhibit but delays liver regeneration after PHX secondary to delayed cyclin D1 activation.
Life Stress and Cardiovascular Disorders
Authors: HAROLD G. WOLFF
Journal: Circulation (1950)

An amassing body of data demonstrates further the growing importance to medicine of the recognition that, for man, reactions to threats in the form of symbols, especially when sustained, may be more important than response to assaults. Certainly, many aspects of cardiovascular disease may be looked upon as functions of man's goals, his methods of achieving them, and the conflicts they engender. In this paper the importance of life stress to the cardiovascular system in various conditions is discussed; case examples demonstrate the relationship between stressful situations and circulatory efficiency, faulty exercise tolerance in patients with or without structural heart disease, the hypodynamic response, cardiac arrhythmias, electrocardiogram, blood pressure, hypertension and renal blood flow.
Faisabilité, tolérance et acceptabilité des coloscopies réalisées au cours d'une analgésie par nefopam et protoxyde d'azote
Authors: JP Farmachidi, A Dusoleil, S Ramsang Kella, JL Walcker, V Lhomme Gettler
Journal: Endoscopy (2008)

Objectif: En France, la coloscopie se fait fréquemment sous anesthésie générale. Or l'accès rapide à l'anesthésie est parfois difficile dans de petites structures hospitalières. Notre objectif était de diminuer le recours à l'anesthésiste et au plateau technique du bloc opératoire en évaluant une analgésie associant une inhalation de protoxyde d'azote et une perfusion de nefopam.
Cytotoxic Chemotherapy in Advanced Non-Small Cell Lung Cancer
Authors: Mark A. Socinski
Journal: Clinical Cancer Research (2004)

Abstract A 1995 meta-analysis of nine trials involving 1190 patients by the Non-Small Cell Lung Cancer Collaborative Group reported that in advanced metastatic disease, platinum-based chemotherapy provides a survival benefit compared with best supportive care. Since then, several randomized trials using either platinum-based combination regimens or selected new single agents have confirmed this observation of a modest survival advantage, as well as improved quality of life. New agents such as paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan have shown significant single-agent activity in advanced non-small cell lung cancer. Two recent meta-analyses have suggested that regimens including these newer agents offer modest improvement in outcomes compared with older regimens. Several randomized trials have evaluated these modern platinum-based doublets and suggested that no one combination is superior when using survival as the primary measure of outcome. Future research may improve outcomes through identifying prognostic markers of treatment response to both standard cytotoxic and newer “targeted” therapies.
Twelve month outcome of depression in general practice: does detection or disclosure make a difference?
Authors: C. Dowrick, I. Buchan
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objectives</b> : To assess the extent to which the outcome of depression among primary care attenders may be affected by medical diagnosis or by feedback of questionnaire results in unrecognised cases. <b>Design</b> : Prospective 12 month study including a randomised controlled trial of the effects of disclosure, with data on depression status and clinical management collected by questionnaire and interview. <b>Setting</b> : Two group practices in north Liverpool. <b>Subjects</b> : 1099/1444 (76%) consecutive adult attenders completed the Beck depression inventory, of whom 179 with scores of at least 14 were followed up. <b>Interventions</b> : Disclosure of a random 45% (52/116) of depression scores to general practitioners for subjects whose depression was undetected. <b>Main outcome measures</b> : Depression status estimated by depression score at start of study and at six and 12 months, with subsample validation against ICD−10 criteria. <b>Results</b> : Questionnaire response rates were 76% (136/179) at six months and 68% (122/179) at 12 months and were higher for women than men. The median depression score was 19 (interquartile range 15 to 22) initially, decreasing to 16 (11 to 23) at 12 months. The median depression score decreased significantly (two sided test, P=0.019) in subjects whose depression was unrecognised at the index consultation but increased in those whose depression had been detected by their general practitioners. Disclosure of cases of unrecognised depression to general practitioners had no effect on outcome. Intention to treat was associated with a worse prognosis, although only a minority of subjects received adequate treatment. <b>Conclusions</b> : Disclosure of undetected depression did not improve prognosis. A diagnosis of depression in general practice should be considered simply as a marker of its severity.
Abstract 2375: Rapid unbiased enrichment (negative selection) of circulating non-hematopoietic tumor cells directly from whole blood
Authors: Carrie Peters, Jodie Fadum, Steve Woodside, Karina McQueen, Terry Thomas
Journal: Cancer Research (2012)

Abstract There is increasing interest in analyzing circulating non-hematopoietic tumor cells (CTC) in peripheral blood to evaluate disease progression or response to treatment; however, CTC enrichment is required prior to most analytic procedures. The ideal enrichment method would be rapid, permit a high recovery of viable CTC, and would be independent of the expression of specific epithelial cell surface markers, since CTCs in the peripheral blood may be undergoing EMT (epithelial mesenchymal transition) and may not express epithelial markers. RosetteSep™ CD45 depletion of hematopoietic cells directly from whole blood meets these criteria. However, RosetteSep™ enrichment of CTC involves density gradient centrifugation, which entails careful layering of the sample over the density gradient medium and careful pipetting to remove the enriched cells after centrifugation. Centrifugation must be performed with the brake off to avoid disturbing the enriched cell layer, further lengthening the process. SepMate™, a centrifugation tube with a specialized insert, was developed to minimize mixing of the sample with the density gradient medium, thus allowing rapid layering of the sample on the density gradient medium and easy pouring off of the enriched cells after centrifugation. We compared CTC enrichment using RosetteSep™ and the standard tubes and protocol with RosetteSep™ using SepMate™ tubes and reduced cocktail incubation and spin times on 5 donor whole blood samples seeded with ∼1% CAMA cells. Purity of viable (PI negative) CTC obtained with SepMate™ with RosetteSep™ was 85 ± 7%; purity of CTC obtained with RosetteSep™ alone was 91 ± 5% (no significant difference, paired t test, p=0.050). Purity of CTC obtained with density gradient centrifugation only (no RosetteSep™), either with or without SepMate™, was 4 ± 2%. There was no significant difference in the recovery of enriched CTC under any of the conditions tested (RosetteSep™ ± SepMate™, SepMate™ alone, density gradient separation alone, Tukey-Kramer test, p&amp;gt;0.05). CTC enrichment was accomplished in &amp;lt;40 min using SepMate™ with RosetteSep™. Simplifying the layering and layer removal step makes the entire process easily scalable to processing multiple samples simultaneously. Utilizing this method, CTCs can be enriched directly from whole blood without bias regarding their surface antigen expression. Large samples can be rapidly volume-reduced in preparation for detailed examination in a microfluidic device. Finally, enriched CTC are not labeled with antibodies or beads; there is nothing to interfere with subsequent further enrichment, culture, or evaluation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2375. doi:1538-7445.AM2012-2375
Seromarkers of collagen I and III metabolism in active Crohn's disease. Relation to disease activity and response to therapy.
Authors: J Kjeldsen, O B Schaffalitzky de Muckadell, P Junker
Journal: Gut (1995)

Crohn9s disease is characterised by gradual development of intestinal fibrotic lesions containing large amounts of collagen type I, III, and V. Measurement of circulating connective tissue metabolites has emerged as a useful tool for assessment of fibroproliferative activity in various diseases. Serum concentrations of procollagen peptides, N-terminal propeptide of type III procollagen (PII-INP), and C-terminal propeptide of type I procollagen (PICP), reflect the synthesis rate of the parent collagens, while the C-terminal telopeptide of type I collagen (ICTP) reflects its degradation. S-PIIINP, S-PICP, and S-ICTP were measured by radioimmunoassays in 29 patients with active Crohn9s disease. S-ICTP was significantly increased, median 6.2 micrograms/l (95% CI 5.2 to 8.7 micrograms/l) versus controls 2.6 micrograms/l (2.5 to 2.7 micrograms/l) (p &lt; 0.0001), S-PICP reduced, 100 micrograms/l (80 to 110 micrograms/l) versus 132 micrograms/l (124 to 141 micrograms/l) (p = 0.001), and S-PIIINP did not differ from controls. Patients with sustained clinical remission during prednisolone therapy exhibited an increase in S-PICP (p = 0.0052). S-PIIINP changed significantly (p = 0.0002), however, exhibiting a biphasic pattern. S-ICTP decreased (p = 0.015) in treatment responders but remained above the upper normal limit even when clinical remission had been achieved. Non-responders showed no significant changes in any of the marker molecules of collagen synthesis or degradation. Correlations were found between S-PIIINP and S-PICP (p &lt; 0.005) and S-ICTP (p &lt; 0.02), and between S-ICTP and S-orosomucoid (p &lt; 0.005) and S-C reactive protein (p &lt; 0.02). By contrast, there was no relation between the connective tissue metabolites and Harvey Bradshaw Index. These data provide evidence that collagen I degradation is increased not only in active Crohn9s disease, but also in patients entering clinical remission. The concurrent normal/low-normal values of markers of collagen formation may reflect a changed local or systemic elimination of the propeptides.
Hazardous wastes in Eastern and Central Europe [meeting report]
Authors: D O Carpenter, W A Suk, K Blaha, M Cikrt
Journal: Environmental Health Perspectives (1996)

The countries of Eastern and Central Europe have emerged from a political system which for decades has ignored protection of human health from hazardous wastes. While the economies of the countries in this region are stretched, awareness and concern about hazardous waste issues are a part of the new realities. At a recent conference sponsored in part by the National Institute of Environmental Health Sciences, representatives of seven countries in the region described the status of hazardous waste programs, issues of major concern, and steps being taken to protect human health. This report summarizes the deliberations, outlines some of the problems remaining in dealing with the legacy of the past, addressing the problems of the present, and providing a framework for future research and collaborative efforts.
A Randomised Controlled Trial of Artemether-Lumefantrine Versus Artesunate for Uncomplicated Plasmodium falciparum Treatment in Pregnancy
Authors: Rose McGready, Saw Oo Tan, Elizabeth A Ashley, Mupawjay Pimanpanarak, Jacher Viladpai-nguen, Lucy Phaiphun, Katja Wüstefeld, Marion Barends, Natthapon Laochan, Lily Keereecharoen, Niklas Lindegardh, Pratap Singhasivanon, Nicholas J White, François Nosten
Journal: PLoS Medicine (2008)

Background To date no comparative trials have been done, to our knowledge, of fixed-dose artemisinin combination therapies (ACTs) for the treatment of Plasmodium falciparum malaria in pregnancy. Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world. The objective of this study was to compare the efficacy, tolerability, and safety of artemether-lumefantrine, the most widely used fixed ACT, with 7 d artesunate monotherapy in the second and third trimesters of pregnancy. Methods and Findings An open-label randomised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d (AL) or artesunate monotherapy 7 d (AS7) was conducted in Karen women in the border area of northwestern Thailand who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy. The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery, as estimated by Kaplan-Meier survival analysis. Infants were assessed at birth and followed until 1 y of life. Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy. Both regimens were very well tolerated. The cure rates (95% confidence interval) for the intention to treat (ITT) population were: AS7 89.2% (82.3%–96.1%) and AL 82.0% (74.8%–89.3%), p = 0.054 (ITT); and AS7 89.7% (82.6%–96.8%) and AL 81.2% (73.6%–88.8%), p = 0.031 (per-protocol population). One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up. Birth outcomes and infant (up to age 1 y) outcomes did not differ significantly between the two groups. The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL. Conclusion The current standard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with uncomplicated falciparum malaria, but efficacy was inferior to 7 d artesunate monotherapy and was unsatisfactory for general deployment in this geographic area. Reduced efficacy probably results from low drug concentrations in later pregnancy. A longer or more frequent AL dose regimen may be needed to treat pregnant women effectively and should now be evaluated. Parasitological endpoints in clinical trials of any antimalarial drug treatment in pregnancy should be extended to delivery or day 42 if it comes later. Trial Registration: Current Controlled Trials ISRCTN86353884.
β-Adrenergic Blockers and Survival in Heart Failure
Authors: Marc A. Pfeffer, Lynne W. Stevenson
Journal: New England Journal of Medicine (1996)

Only in the past decade have well-conducted clinical trials advanced the treatment of congestive heart failure from palliation to prolongation of life. In 1986, the Veterans Administration Cooperative Vasodilator–Heart Failure Trial I (V-HeFT I) established the principle that medical therapy (with hydralazine plus nitrates) could prolong survival in patients with symptomatic heart failure.1 On the heels of that study, angiotensin-converting–enzyme (ACE) inhibitors were definitively shown to improve survival in the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) and the Studies of Left Ventricular Dysfunction (SOLVD).2,3 V-HeFT II then compared these therapies directly and showed that the survival benefit was . . .
Variability in end of life care
Authors: Diane E Meier
Journal: BMJ (2004)

What does it tell us about quality? 

What is the “right” amount of medical care? In this issue of BMJ USA (p 231), Wennberg and colleagues document significant variability in care delivered by USacademic health centers to Medicare patients during the last six months of their lives. The study shows that the best quality academic teaching hospitals, as ranked by US News and World Report , vary in the amount and types of care they provide to the seriously ill. Medicare decedents' average days in hospital, days in intensive care, number of physician visits and physicians seen, hospice enrollment rates, and deaths in intensive care differed greatly among these highly ranked teaching hospitals.

These findings are not unique to academic medical centers. The same investigators have documented similar regional variation in clinical practice in other hospital types, and the patterns suggest a strong influence on local practice patterns of opinion leaders, market forces, local medical culture, hospital and ICU bed availability, and access to specialists. It is perhaps not surprising that practice patterns within academic …
Kinesiogenic Choreoathetosis and Idiopathic Hypoparathyroidism
Authors: M. J. Tabaee-Zadeh, Boy Frame, Kenneth Kapphahn
Journal: New England Journal of Medicine (1972)

INVOLUNTARY motor derangements and calcification of the basal ganglions as manifestations of hypoparathyroidism have received periodic attention in the medical literature. The patient described below had an unusual paroxysmal motor disturbance due to idiopathic hypoparathyroidism that was corrected with vitamin D.Case SummaryA 30-year-old man had an 11-year history of spells characterized by a sudden tonic contraction of the head, right arm and leg (Fig. 1) occurring several times each week only after vigorous activity such as running or dancing, lasting about 30 seconds and unassociated with premonitory symptoms or sequelae. During the height of the abnormal posture there . . .
HL-A antigens in lichen planus
Authors: N.J. LOWE, A.G. CUDWORTH, J.C. WOODROW
Journal: British Journal of Dermatology (1976)

A Study of fifty-seven patients with lichen planus showed a significant increase in the frequency of HL-A 3 (54% compared with 29.7% in a control population). It is likely that there is a gene in the HL-A chromosomal region increasing the susceptibility to lichen planus. No correlation was found between HL-A 3 and age of onset, sex, and presence or absence of mucosal lesions.
Passive ventricular restraint with nitinol mesh attenuates remodeling following acute myocardial infarction
Authors: Leah A. Teekell-Taylor, Sunil Mankad, Uday Dasika, Walter E. McGregor, Robert W.W. Biederman, June Yamrozik, Dennis R. Trumble, James A. Magovern
Journal: Journal of the American College of Cardiology (2002)
HL-A ANTIGENS IN INFLAMMATORY BOWE DISEASE
Authors: R.M. Lewkonia, J.C. Woodrow, R.B. Mcconnell, D.A. Price Evans, P. Asquith, Pauline Mackintosh, P.L. Stokes, G.K.T. Holmes, W.T. Cooke, K.W. Cross
Journal: The Lancet (1974)
The role of H-2-linked genes in helper T-cell function. VI. Expression of Ir genes by helper T cells.
Authors: P Marrack, J W Kappler
Journal: The Journal of Experimental Medicine (1979)

We examined the expression of (TG)-A--L specific Ir genes in helper T cells using T cells from low responder leads to (B10, high responder x low responder) F1 chimeric mice. In this paper, the low responder strain studied was B10.M, H-2f. B10.M T cells from these chimeric animals do not help anti-TNP-(TG)-A--L responses, even though they have matured in a high responder thymus and been primed and challenged with antigen on high responder Mphi and B cells. These findings indicate that in the H-2f haplotype an Ir-gene controlling anti-(TG)-A--L activity is expressed in helper T cells. The findings are in contrast to those we have obtained and previously reported with T cells of another low responder haplotype, H-2a. Taken together with our previous findings that (TG)-A--L specific Ir genes are expressed by B cells and Mphi of both the H-2a and H-2f haplotypes, the results indicate two sites of action for Ir genes, and suggest two different gene products acting at different stages of the response, both of which are defective in H-2f cells, and only one of which is defective in H-2a cells.
A prospective study of the natural history of transient leukemia (TL) in neonates with Down syndrome (DS): Children's Oncology Group (COG) study POG-9481
Authors: Gita V. Massey, Alvin Zipursky, Myron N. Chang, John J. Doyle, Suhail Nasim, Jeffrey W. Taub, Yaddanapudi Ravindranath, Gary Dahl, Howard J. Weinstein
Journal: Blood (2006)
Deletions of immunoglobulin C kappa region characterized by the circular excision products in mouse splenocytes.
Authors: T Shimizu, T Iwasato, H Yamagishi
Journal: The Journal of Experimental Medicine (1991)

We have identified circular DNAs containing the kappa light chain constant region (C kappa), as well as the excision products of V kappa-J kappa and V lambda-J lambda joining in adult mouse splenocytes. Analysis of C kappa-positive circular DNA clones revealed two recombination sites (intron recombining sequence [IRS]1 and -2) within the germline J kappa-C kappa intron region and the recombining sequence (RS) located downstream of the C kappa exon. While RS contains a conserved heptamer and nonamer separated by a 23-bp spacer on the 5' side, IRS1 sequence is an isolated heptamer without an obvious nonamer, and IRS2 contains a variant heptamer, CACAAAA. Since IRS1 and IRS2 recombined with both RS (23-bp spacer signal) and V kappa (12-bp spacer signal) with significant frequency, intron recombination sites seem to have dual recombination signals. These findings provide direct evidence that C kappa deletion preceding lambda gene rearrangement can occur by looping out and excision. Increased accessibility of inefficient recombinational loci within the intron may enable recombinase to accept wide signal sequence variation.