tbuckley/cabot-search huggingface dataset:
Plasma glutathione S-transferase measurements after paracetamol overdose: evidence for early hepatocellular damage.
Authors: G J Beckett, B J Chapman, E H Dyson, J D Hayes
Journal: Gut (1985)

Plasma glutathione S-transferase (GST) measurements have been used to study early changes in hepatocellular integrity after paracetamol overdose and treatment with N-acetylcysteine (NAC). Patients admitted within seven hours and successfully treated had raised or equivocal GST on admission and each showed a transient peak in GST approximately 12 hours after the overdose. Similar, though smaller changes in GST, were seen in untreated patients whose paracetamol level fell below the treatment line. The plasma GST concentrations in successfully treated patients were small compared with values found in patients who subsequently developed severe liver damage. The changes in GST concentration observed in patients who developed severe liver damage indicated that distinct early and late phases of paracetamol-induced hepatotoxicity occurred. Although the mechanism by which paracetamol exerts its early toxic effect is unclear, our data suggest that prompt treatment with NAC can successfully prevent both clinical and subclinical hepatotoxicity in this early period.
PROGNOSTIC PREDICTIVE VALUE OF EXERCISE-INDUCED CHANGES OF PLASMA NT-PROBNP AND NOREPINEPHRINE IN PATIENTS WITH HEART FAILURE
Authors: Dario Leosco, Grazia Daniela Femminella, Valentina Parisi, Gennaro Pagano, Claudio de Lucia, Alessandro Cannavo, Daniela Liccardo, Klara Komici, Roberto Formisano, Zincarelli Carmela, Nicola Ferrara, Giuseppe Rengo
Journal: Journal of the American College of Cardiology (2013)
Only women with symptoms need to have their breast implants removed, says government
Authors: A. O'Dowd
Journal: BMJ (2012)

The government is playing down the need for women who have breast implants made by a discredited French company to have them removed, in an attempt to lessen continuing fears about their safety.

The Department of Health for England has issued fresh advice and paid around £135 000 (€160 000; $210 000) for a public advertising campaign to try to clarify the issue.

Around 40 000 women in the United Kingdom are thought to have the implants made by the French company Poly Implant Prosthese (PIP), which closed after it emerged that it had used non-medical grade silicone.

The UK government commissioned an expert review, which last month concluded that women with the implants should not have them removed automatically but could seek clinical advice. If they …
CD8α+ dendritic cells originate from the CD8α− dendritic cell subset by a maturation process involving CD8α, DEC-205, and CD24 up-regulation
Authors: Gloria Martı́nez del Hoyo, Pilar Martı́n, Cristina Fernández Arias, Alvaro Rodrı́guez Marı́n, Carlos Ardavı́n
Journal: Blood (2002)
Evidence in Favor of a Calcium-Sensing Receptor in Arterial Endothelial Cells
Authors: Arthur H. Weston, Mais Absi, Donald T. Ward, Jacqueline Ohanian, Robert H. Dodd, Philippe Dauban, Christophe Petrel, Martial Ruat, Gillian Edwards
Journal: Circulation Research (2005)

Small increases in extracellular Ca 2+ dilate isolated blood vessels. In the present study, the possibility that a vascular, extracellular Ca 2+ -sensing receptor (CaSR) could mediate these vasodilator actions was investigated. Novel ligands that interact with the CaSR were used in microelectrode recordings from rat isolated mesenteric and porcine coronary arteries. The major findings were that (1) raising extracellular Ca 2+ or adding calindol, a CaSR agonist, produced concentration-dependent hyperpolarizations of vascular myocytes, actions attenuated by Calhex 231, a negative allosteric modulator of CaSR. (2) Calindol-induced hyperpolarizations were inhibited by the intermediate conductance, Ca 2+ -sensitive K + (IK Ca ) channel inhibitors, TRAM-34, and TRAM-39. (3) The effects of calindol were not observed in the absence of endothelium. (4) CaSR mRNA and protein were present in rat mesenteric arteries and in porcine coronary artery endothelial cells. (5) CaSR and IK Ca proteins were restricted to caveolin-poor membrane fractions. We conclude that activation of vascular endothelial CaSRs opens endothelial cell IK Ca channels with subsequent myocyte hyperpolarization. The endothelial cell CaSR may have a physiological role in the control of arterial blood pressure.
Effects of intramuscular microsphere-encapsulated octreotide on serum growth hormone, insulin-like growth factors (IGFs), free IGFs, and IGF-binding proteins in acromegalic patients
Authors: A. Kaal, J. Frystyk, C. Skjærbæk, S. Nielsen, J.O.L. Jørgensen, C. Bruns, P. Marbach, I. Lancranjan, J. Weeke, H. Ørskov
Journal: Metabolism (1995)
A strategy for end of life care in the UK
Authors: J. Riley
Journal: BMJ (2008)

We need to overcome taboos about death and communicate better

Around 500 000 people die in England each year, and this number is predicted to rise to around 530 000 by 2030. Death affects every person, family, and community, and every culture and creed has its own way of dealing with it. We should all have an interest in good end of life care, yet death is not culturally acceptable, and it is a taboo subject to the public and the medical profession. In a recent BBC survey, only 34% of the general public reported that they had discussed their wishes for how they would like to die. Many healthcare professionals consider it a failure when patients die. In April 2008, the Heath Commission reported that no less than 54% of complaints related in some way to end of life care.

Last week the Department of Health published its strategy for dealing with end of life care in the United Kingdom.1 Producing such a strategy is challenging because it incorporates health care, social care, spiritual care, and all possible sensitivities, as well as homeless people, prisoners, and mentally disabled people. More than 300 stakeholders were consulted. We need …
"Are you depressed?" Screening for depression in the terminally ill
Authors: H M Chochinov, K G Wilson, M Enns, S Lander
Journal: American Journal of Psychiatry (1997)

Objective: This study compared the performance of four brief screening measures for depression in a group of terminally ill patients.The methods included 1) a single-item interview assessing depressed mood, 2) a two-item interview assessing depressed mood and loss of interest in activities, 3) a visual analog scale for depressed mood, and 4) the Beck Depression Inventory-Short Form.Method: Semistructured diagnostic interviews for depression were administered to 197 patients receiving palliative care for advanced cancer.The interview diagnoses served as the standards against which the screening performance of the four brief screening methods was assessed.Results: Single-item interview screening correctly identified the eventual diagnostic outcome of every patient, substantially outperforming the questionnaire and visual analog measures.Conclusions: Brief screening measures for depression are important clinical tools for terminally ill patients.For diagnostic purposes, however, they do not approach the validity of a single-item interview that asks, in effect, "Are you depressed?"
Liver diseases associated with autoantibodies directed to nuclear envelope components
Authors: K. Lassoued, F. Danon, C. André, J. C. Courvalin, D. Dhumeaux, Francisco Lozano, Albert Parés, Luis Borche, Montserrat Plana, Teresa Gallart, Joan Rodés, Jordi Vives
Journal: Hepatology (1989)
Effect of functional nuclear factor-kappaB genetic polymorphisms on hepatitis B virus persistence and their interactions with viral mutations on the risk of hepatocellular carcinoma
Authors: Q Zhang, X W Ji, X M Hou, F M Lu, Y Du, J H Yin, X Y Sun, Y Deng, J Zhao, X Han, G S Yang, H W Zhang, X M Chen, H B Shen, H Y Wang, G W Cao
Journal: Annals of Oncology (2014)
<i>KRAS</i> Mutation in Stage III Colon Cancer and Clinical Outcome Following Intergroup Trial CALGB 89803
Authors: Shuji Ogino, Jeffrey A. Meyerhardt, Natsumi Irahara, Donna Niedzwiecki, Donna Hollis, Leonard B. Saltz, Robert J. Mayer, Paul Schaefer, Renaud Whittom, Alexander Hantel, Al B. Benson, Richard M. Goldberg, Monica M. Bertagnolli, Charles S. Fuchs
Journal: Clinical Cancer Research (2009)

Alterations in the RAS and RAF pathway relate to epigenetic and epigenomic aberrations, and are important in colorectal carcinogenesis. KRAS mutation in metastatic colorectal cancer predicts resistance to anti-epidermal growth factor receptor (EGFR)-targeted therapy (cetuximab or panitumumab). It remains uncertain, however, whether KRAS mutation predicts prognosis or clinical outcome of colon cancer patients independent of anti-EGFR therapy.
Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.
Authors: S Ylä-Herttuala, W Palinski, M E Rosenfeld, S Parthasarathy, T E Carew, S Butler, J L Witztum, D Steinberg
Journal: Journal of Clinical Investigation (1989)

Three lines of evidence are presented that low density lipoproteins gently extracted from human and rabbit atherosclerotic lesions (lesion LDL) greatly resembles LDL that has been oxidatively modified in vitro. First, lesion LDL showed many of the physical and chemical properties of oxidized LDL, properties that differ from those of plasma LDL: higher electrophoretic mobility, a higher density, higher free cholesterol content, and a higher proportion of sphingomyelin and lysophosphatidylcholine in the phospholipid fraction. A number of lower molecular weight fragments of apo B were found in lesion LDL, similar to in vitro oxidized LDL. Second, both the intact apo B and some of the apo B fragments of lesion LDL reacted in Western blots with antisera that recognize malondialdehyde-conjugated lysine and 4-hydroxynonenal lysine adducts, both of which are found in oxidized LDL; plasma LDL and LDL from normal human intima showed no such reactivity. Third, lesion LDL shared biological properties with oxidized LDL: compared with plasma LDL, lesion LDL produced much greater stimulation of cholesterol esterification and was degraded more rapidly by macrophages. Degradation of radiolabeled lesion LDL was competitively inhibited by unlabeled lesion LDL, by LDL oxidized with copper, by polyinosinic acid and by malondialdehyde-LDL, but not by native LDL, indicating uptake by the scavenger receptor(s). Finally, lesion LDL (but not normal intimal LDL or plasma LDL) was chemotactic for monocytes, as is oxidized LDL. These studies provide strong evidence that atherosclerotic lesions, both in man and in rabbit, contain oxidatively modified LDL.
Paradoxes in Advance Care Planning: The Complex Relationship of Oncology Patients, Their Physicians, and Advance Medical Directives
Authors: Lindsay A. Dow, Robin K. Matsuyama, V. Ramakrishnan, Laura Kuhn, Elizabeth B. Lamont, Laurel Lyckholm, Thomas J. Smith
Journal: Journal of Clinical Oncology (2009)

Many seriously ill patients with cancer do not discuss prognosis or advance directives (ADs), which may lead to inappropriate and/or unwanted aggressive care at the end of life. Ten years ago, patients with cancer said they would not like to discuss ADs with their oncologist but would be willing to discuss them with an admitting physician. We assessed whether this point of view still held.Semi-structured interviews were conducted with 75 consecutively admitted patients with cancer in the cancer inpatient service.Of those enrolled, 41% (31 of 75) had an AD. Nearly all (87%, 65 of 75) thought it acceptable to discuss ADs with the admitting physician with whom they had no prior relationship, and 95% (62 of 65) thought that discussing AD issues was very or somewhat important. Only 7% (5 of 75) had discussed ADs with their oncologist, and only 23% (16 of 70) would like to discuss ADs with their oncologist. When specifically asked which physician they would choose, 48% (36 of 75) of patients would prefer their oncologist, and 35% (26 of 75) would prefer their primary care physician.Fewer than half of seriously ill patients with cancer admitted to an oncology service have an AD. Only 23% (16 of 70) would like to discuss their ADs with their oncologist but nearly all supported a policy of discussing ADs with their admitting physician. However, fully 48% (36 of 75) actually preferred to discuss advance directives with their oncologist if AD discussion was necessary. We must educate patients on why communicating their ADs is beneficial and train primary care physicians, house staff, hospitalists, and oncologists to initiate these difficult discussions.
Inhibitory role of dietary protein restriction on the development and expression of immune-mediated antitubular basement membrane-induced tubulointerstitial nephritis in rats.
Authors: D Agus, R Mann, D Cohn, L Michaud, C Kelly, M Clayman, E G Neilson
Journal: Journal of Clinical Investigation (1985)

The protective effect of dietary protein restriction on the development and expression of immune-mediated interstitial nephritis was evaluated in Brown Norway rats with anti-tubular basement membrane disease. In the first series of experiments, pair-fed rats received low protein (LP) (3% casein) or normal protein (NP) (27% casein), normocaloric diets. After 6 wk, each group was immunized with renal tubular antigen in adjuvant to produce anti-tubular basement membrane antibody (alpha TBM-Ab) and tubulointerstitial nephritis. The kidneys harvested from NP rats after four more weeks on the diet had histologically more severe interstitial disease than the LP rats (histologic severity; NP = 3.1 +/- 0.2 vs. LP = 1.1 +/- 0.3; P less than 0.001), and serum creatinine values were concordantly different (NP = 1.34 +/- 0.02 vs. LP = 0.82 +/- 0.03). Titers of alpha TBM-Ab were similar in both groups, while the T cell-mediated immune response, as measured by delayed-type hypersensitivity (DTH), was nonspecifically impaired in LP rats when compared with the NP group. Admixture cotransfers of LP plus NP cells failed to demonstrate active suppression as an explanation for the depressed DTH in LP rats. The therapeutic role of dietary protein restriction was also examined in rats with established alpha TBM disease. In these experiments, rats were first immunized and fed NP diets for 4 wk (histologic severity = 3.0 +/- 0.2; creatinine = 1.78 +/- 0.02), and then were divided into two groups and followed for six more weeks on either LP or NP diets. LP rats, under these conditions, developed less disease than those fed NP diet (histologic severity; NP = 3.2 +/- 0.3 vs. LP = 1.4 +/- 0.2; P less than 0.001), and serum creatinine values were concordantly different (NP = 1.92 +/- 0.05 vs. LP = 0.97 +/- 0.02). Again, the titers of alpha TBM-Ab in both LP and NP groups were similar. These data collectively suggest that LP diet has a protective effect both on the development and extent of tubulointerstitial nephritis that is perhaps, in part, related to the selective abrogation of effector T cell immunity.
Association of Trauma and PTSD Symptoms With Openness to Reconciliation and Feelings of Revenge Among Former Ugandan and Congolese Child Soldiers
Authors: Christophe Pierre Bayer, Fionna Klasen, Hubertus Adam
Journal: JAMA (2007)

Tens of thousands of the estimated 250,000 child soldiers worldwide are abused or have been abused during the last decade in Africa's Great Lakes Region. In the process of rebuilding the war-torn societies, it is important to understand how psychological trauma may shape the former child soldiers' ability to reconcile.To investigate the association of posttraumatic stress disorder (PTSD) symptoms and openness to reconciliation and feelings of revenge in former Ugandan and Congolese child soldiers.Cross-sectional field study of 169 former child soldiers (aged 11-18 years) in rehabilitation centers in Uganda and the Democratic Republic of the Congo, conducted in 2005.Potentially traumatic war-related experiences assessed via a sample-specific events scale; PTSD symptoms assessed using the Child Posttraumatic Stress Disorder Reaction Index (CPTSD-RI), with a score of 35 or higher indicating clinically important PTSD symptoms; and openness to reconciliation and feelings of revenge assessed via structured questionnaires.Children participating in this study were a mean of 15.3 years old. These former child soldiers reported that they had been (violently) recruited by armed forces at a young age (mean [SD], 12.1 [2] years), had served a mean of 38 months (SD, 24 months), and had been demobilized a mean of 2.3 months before data collection (SD, 2.4 months). The children were exposed to a high level of potentially traumatic events (mean [SD], 11.1 [2.99]). The most commonly reported traumatic experiences were having witnessed shooting (92.9%), having witnessed someone wounded (89.9%), and having been seriously beaten (84%). A total of 54.4% reported having killed someone, and 27.8% reported that they were forced to engage in sexual contact. Of the 169 interviewed, 59 (34.9%; 95% confidence interval, 34.4%-35.4%) had a PTSD symptom score higher than 35. Children who showed more PTSD symptoms had significantly less openness to reconciliation (rho= -0.34, P < .001) and more feelings of revenge (rho= 0.29, P < .001).PTSD symptoms are associated with less openness to reconciliation and more feelings of revenge among former Ugandan and Congolese child soldiers. The effect of psychological trauma should be considered when these children are rehabilitated and reintegrated into civilian society.
Exercise therapy may postpone total hip replacement surgery in patients with hip osteoarthritis: a long-term follow-up of a randomised trial
Authors: Ida Svege, Lars Nordsletten, Linda Fernandes, May Arna Risberg
Journal: Annals of the Rheumatic Diseases (2013)

Background Exercise treatment is recommended for all patients with hip osteoarthritis (OA), but its effect on the long-term need for total hip replacement (THR) is unknown. Methods We conducted a long-term follow-up of a randomised trial investigating the efficacy of exercise therapy and patient education versus patient education only on the 6-year cumulative survival of the native hip to THR in 109 patients with symptomatic and radiographic hip OA. Results regarding the primary outcome measure of the trial, self-reported pain at 16 months follow-up, have been reported previously. Results There were no group differences at baseline. The response rate at follow-up was 94%. 22 patients in the group receiving both exercise therapy and patient education and 31 patients in the group receiving patient education only underwent THR during the follow-up period, giving a 6-year cumulative survival of the native hip of 41% and 25%, respectively (p=0.034). The HR for survival of the native hip was 0.56 (CI 0.32 to 0.96) for the exercise therapy group compared with the control group. Median time to THR was 5.4 and 3.5 years, respectively. The exercise therapy group had better self-reported hip function prior to THR or end of study, but no significant differences were found for pain and stiffness. Conclusions Our findings in this explanatory study suggest that exercise therapy in addition to patient education can reduce the need for THR by 44% in patients with hip OA. ClinicalTrials.gov number NCT00319423 (original project protocol) and NCT01338532 (additional protocol for long-term follow-up).
Limited use of interleukin 28B in the setting of response-guided treatment with detailed on-treatment virological monitoring
Authors: Alessandra Mangia, Alexander J. Thompson, Rosanna Santoro, Valeria Piazzolla, Massimiliano Copetti, Nicola Minerva, Daniela Petruzzellis, Leonardo Mottola, Donato Bacca, John G. McHutchison
Journal: Hepatology (2011)

A single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene is associated with pegylated interferon-alfa-induced viral clearance in hepatitis C virus (HCV) genotype 1 patients. Using a well-characterized cohort of patients randomized to standard versus response-guided therapy, we studied whether the favorable CC type allows shortening of treatment duration. Association with viral kinetics, sustained viral response (SVR), and predictors of response were also analyzed. In the original study, 696 patients were randomized to either standard or variable therapy of 24, 48, or 72 weeks according to first undetectable HCV RNA. Association between IL28B determined by genotyping rs12979860 and end of treatment response and SVR by treatment arm was tested; baseline predictors of response were analyzed using multiple logistic regression. A total of 454 patients were evaluated. The frequency of IL28B type was CC = 29%, CT = 53%, TT = 18%. CC type was strongly associated with rapid virological response (RVR) as well as higher rates of week 8 and week 12 response. CC type was associated with SVR in both arms. In patients with RVR, SVR was high and IL28B type was not associated with SVR. In RVR patients, there was no significant difference in SVR or relapse rates after 24 or 48 weeks by IL28B type. Among non-RVR patients, CC type was associated with SVR at a higher rate than CT/TT, both in standard and variable analysis. However, when week 8 and week 12 responders were considered separately, IL28B type was no longer predictive of SVR. Few CC patients remained viremic beyond week 8 to allow the analysis of relationships between IL28B type and extended treatment.In HCV-1 patients, the favorable CC type strongly predicted higher rates of on-treatment virological milestones and SVR. However, achievement of on-treatment virological milestones was the critical factor in determining outcome. IL28B type appeared to have limited potential for response-guided treatment strategies.
Loss of T-bet, But Not STAT1, Prevents the Development of Experimental Autoimmune Encephalomyelitis
Authors: Estelle Bettelli, Brandon Sullivan, Susanne J. Szabo, Raymond A. Sobel, Laurie H. Glimcher, Vijay K. Kuchroo
Journal: The Journal of Experimental Medicine (2004)

The transcription factors signal transducer and activator of transcription (STAT)1 and T-bet control the differentiation of interferon (IFN)-γ–producing T helper type (Th)1 cells. Here we compare the role of T-bet and STAT1 in the initiation and regulation of experimental autoimmune encephalomyelitis (EAE), a disease initiated by Th1 cells. T-bet–deficient mice immunized with myelin oligodendrocyte glycoprotein (MOG) were resistant to the development of EAE. This protection was also observed when T-bet−/− mice were crossed to the MOG-specific 2D2 T cell receptor transgenic strain. In contrast, although T-bet is downstream of STAT1, STAT1−/− mice were highly susceptible to EAE and developed more severe and accelerated disease with atypical neuropathologic features. The function of T-bet was dominant as mice deficient in both T-bet and STAT1 were also protected from EAE. CD4+ CD25+ regulatory T cells from these two mice strains were fully competent and do not explain the difference in disease susceptibility. However, enhanced EAE in STAT1−/− mice was associated with continued generation of IFN-γ–producing Th1 cells and up-regulation of selective chemokines responsible for the increased recruitment of macrophages and neutrophils in the central nervous system. Although the two transcription factors, STAT1 and T-bet, both induce IFN-γ gene transcription, our results demonstrate marked differences in their function in regulating pathogenic Th1 cell responses.