tbuckley/cabot-search huggingface dataset:
Reducing Hospital Readmission Rates: Current Strategies and Future Directions
Authors: Sunil Kripalani, Cecelia N. Theobald, Beth Anctil, Eduard E. Vasilevskis
Journal: Annual Review of Medicine (2013)

New financial penalties for institutions with high readmission rates have intensified efforts to reduce rehospitalization. Several interventions that involve multiple components (e.g., patient needs assessment, medication reconciliation, patient education, arranging timely outpatient appointments, and providing telephone follow-up) have successfully reduced readmission rates for patients discharged to home. The effect of interventions on readmission rates is related to the number of components implemented; single-component interventions are unlikely to reduce readmissions significantly. For patients discharged to postacute care facilities, multicomponent interventions have reduced readmissions through enhanced communication, medication safety, advanced care planning, and enhanced training to manage medical conditions that commonly precipitate readmission. To help hospitals direct resources and services to patients with greater likelihood of readmission, risk-stratification methods are available. Future work should better define the roles of home-based services, information technology, mental health care, caregiver support, community partnerships, and new transitional care personnel.
Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients
Authors: F Bressolle, C Bologna, J M Kinowski, J Sany, B Combe
Journal: Annals of the Rheumatic Diseases (1998)

To determine the effects of impaired renal function on the pharmacokinetics of methotrexate (MTX) in rheumatoid arthritis (RA) patients.77 RA patients were included in this study. MTX was administered intramuscularly (7.5 to 15 mg). Subjects were divided into four groups, according to their creatinine clearance (CLCR); group 1: CLCR lower than 45 ml/min; group 2: CLCR between 45 and 60 ml/min, group 3: CLCR between 61 and 80 ml/min and group 4: CLCR higher than 80 ml/min. Blood samples were collected from each subject before drug administration and at two and eight hours after administration. Individual pharmacokinetic parameters were estimated using a Bayesian approach.MTX concentrations (total and free) were 1.3 to 1.6-times higher in group 1 than in groups 2, 3, and 4. For total and free MTX, t1/2 eliminations were 22.7 hours in group 1, 13.5 hours in group 2, 12 hours in group 3, and 11 hours in group 4. Clearance of total MTX was 64, 92, 96, 115 ml/min in groups 1 to 4, respectively, it was 118, 163, 171, 206 ml/min in groups 1 to 4 for the free MTX, respectively. Volume of distribution averaged 2.16 l/kg in group 1, 1.92 l/kg in group 2, 1.61 l/kg in group 3, and 1.56 l/kg in group 4. Elimination half life was significantly increased and total clearance was significantly reduced with the degree of renal impairment. Linear regression revealed good correlations between clearance values of MTX and creatinine clearance.Individual testing is required rather than a general decrease of the MTX dose based only on CLCR.
XRCC1 suppresses somatic hypermutation and promotes alternative nonhomologous end joining in <i>Igh</i> genes
Authors: Huseyin Saribasak, Robert W. Maul, Zheng Cao, Rhonda L. McClure, William Yang, Daniel R. McNeill, David M. Wilson, Patricia J. Gearhart
Journal: The Journal of Experimental Medicine (2011)

Activation-induced deaminase (AID) deaminates cytosine to uracil in immunoglobulin genes. Uracils in DNA can be recognized by uracil DNA glycosylase and abasic endonuclease to produce single-strand breaks. The breaks are repaired either faithfully by DNA base excision repair (BER) or mutagenically to produce somatic hypermutation (SHM) and class switch recombination (CSR). To unravel the interplay between repair and mutagenesis, we decreased the level of x-ray cross-complementing 1 (XRCC1), a scaffold protein involved in BER. Mice heterozygous for XRCC1 showed a significant increase in the frequencies of SHM in Igh variable regions in Peyer’s patch cells, and of double-strand breaks in the switch regions during CSR. Although the frequency of CSR was normal in Xrcc1+/− splenic B cells, the length of microhomology at the switch junctions decreased, suggesting that XRCC1 also participates in alternative nonhomologous end joining. Furthermore, Xrcc1+/− B cells had reduced Igh/c-myc translocations during CSR, supporting a role for XRCC1 in microhomology-mediated joining. Our results imply that AID-induced single-strand breaks in Igh variable and switch regions become substrates simultaneously for BER and mutagenesis pathways.
Pfetin as a Prognostic Biomarker of Gastrointestinal Stromal Tumors Revealed by Proteomics
Authors: Yoshiyuki Suehara, Tadashi Kondo, Kunihiko Seki, Tatsuhiro Shibata, Kiyonaga Fujii, Masahiro Gotoh, Tadashi Hasegawa, Yasuhiro Shimada, Mitsuru Sasako, Tadakazu Shimoda, Hisashi Kurosawa, Yasuo Beppu, Akira Kawai, Setsuo Hirohashi
Journal: Clinical Cancer Research (2008)

We aimed to develop prognostic biomarkers for gastrointestinal stromal tumors (GIST) using a proteomic approach.We examined the proteomic profile of GISTs using two-dimensional difference gel electrophoresis. The prognostic performance of biomarker candidates was examined using a large-scale sample set and specific antibodies.We identified 43 protein spots whose intensity was statistically different between GISTs with good and poor prognosis. Mass spectrometric protein identification showed that the 43 spots corresponded to 25 distinct gene products. Eight of the 43 spots derived from pfetin, a potassium channel protein, and four of the eight pfetin spots had a high discriminative power between the two groups. Western blotting and real-time PCR showed that pfetin expression and tumor metastasis were inversely related. The prognostic performance of pfetin was also examined by immunohistochemistry on 210 GIST cases. The 5-year metastasis-free survival rate was 93.9% and 36.2% for patients with pfetin-positive and pfetin-negative tumors, respectively (P < 0.0001). Univariate and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinicopathologic variables examined, including risk classification and c-kit- or platelet-derived growth factor receptor A mutation status.These results establish pfetin as a powerful prognostic marker for GISTs and may provide novel therapeutic strategies to prevent metastasis of GIST.
Health Outcomes After Prostatectomy or Radiotherapy for Prostate Cancer: Results From the Prostate Cancer Outcomes Study
Authors: A. L. Potosky
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Radical prostatectomy and external beam radiotherapy are the two major therapeutic options for treating clinically localized prostate cancer. Because survival is often favorable regardless of therapy, treatment decisions may depend on other therapy-specific health outcomes. In this study, we compared the effects of two treatments on urinary, bowel, and sexual functions and on general health-related quality-of-life outcomes over a 2-year period following initial treatment. Methods: A diverse cohort of patients aged 55–74 years who were newly diagnosed with clinically localized prostate cancer and received either radical prostatectomy (n = 1156) or external beam radiotherapy (n = 435) were included in this study. A propensity score was used to balance the two treatment groups because they differed in some baseline characteristics. This score was used in multivariable cross-sectional and longitudinal regression analyses comparing the treatment groups. All statistical tests were two-sided. Results: Almost 2 years after treatment, men receiving radical prostatectomy were more likely than men receiving radiotherapy to be incontinent (9.6% versus 3.5%; P<.001) and to have higher rates of impotence (79.6% versus 61.5%; P<.001), although large, statistically significant declines in sexual function were observed in both treatment groups. In contrast, men receiving radiotherapy reported greater declines in bowel function than did men receiving radical prostatectomy. All of these differences remained after adjustments for propensity score. The treatment groups were similar in terms of general health-related quality of life. Conclusions: There are important differences in urinary, bowel, and sexual functions over 2 years after different treatments for clinically localized prostate cancer. In contrast to previous reports, these outcome differences reflect treatment delivered to a heterogeneous group of patients in diverse health care settings. These results provide comprehensive and representative information about long-term treatment complications to help guide and inform patients and clinicians about prostate cancer treatment decisions.
A Macrophage Invasion Mechanism for Mycobacteria Implicating the Extracellular Domain of Cd43
Authors: Candida Fratazzi, N. Manjunath, Robert D. Arbeit, Claudio Carini, Thomas A. Gerken, Blair Ardman, Eileen Remold-O'Donnell, Heinz G. Remold
Journal: The Journal of Experimental Medicine (2000)

We studied the role of CD43 (leukosialin/sialophorin), the negatively charged sialoglycoprotein of leukocytes, in the binding of mycobacteria to host cells. CD43-transfected HeLa cells bound Mycobacterium avium, but not Salmonella typhimurium or Shigella flexneri. Quantitative bacteriology showed that macrophages (Mφ) from wild-type mice (CD43+/+) bound M. avium, Mycobacterium bovis (bacillus Calmette-Guérin), and Mycobacterium tuberculosis (strain H37Rv), whereas Mφ from CD43 knockout mice (CD43−/−) did not. Fluorescence microscopy demonstrated that the associated M. avium had been ingested by the CD43+/+ Mφ. The inability of CD43−/− Mφ to bind M. avium could be restored by addition of galactoglycoprotein (Galgp), the extracellular mucin portion of CD43. The effect of Galgp is not due to opsonization of the bacteria, but required its interaction with the Mφ; other mucins had no effect. CD43 expression by the Mφ was also required for optimal induction by M. avium of tumor necrosis factor (TNF)-α production, which likewise could be reconstituted by Galgp. In contrast, interleukin (IL)-10 production by M. avium–infected Mφ was CD43 independent, demonstrating discordant regulation of TNF-α and IL-10. These findings describe a novel role of CD43 in promoting stable interaction of mycobacteria with receptors on the Mφ enabling the cells to respond specifically with TNF-α production.
The hepatocyte growth factor regulates the synthesis of acute-phase proteins in human hepatocytes: Divergent effect on interleukin-6-stimulated genes
Authors: M I Guillen, M J Gomez-Lechon, T Nakamura, J V Castell
Journal: Hepatology (1996)

Our study addressed the role of the human hepatocyte growth factor (HGF), a potent mitogen for mature rat and human hepatocytes, in the regulation of specific hepatic genes. The experimental evidence obtained in primary cultured human hepatocytes indicates that HGF regulates the synthesis of plasma proteins in a dose-response fashion. It stimulates the synthesis of the negative acute-phase proteins albumin, transferrin, and fibronectin, decreases that of alpha1-antichymotrypsin (ACT) and haptoglobin, and stimulates that of alpha2-macroglobulin (AMG), which in man is insensitive to inflammatory mediators. HGF had no effect on C-reactive protein (CRP) synthesis. These effects differ from those elicited by interleukin-6 (IL-6). The effects of HGF on fibrinogen and alpha1-antitrypsin were, however, similar to those induced by IL-6. The effects of HGF were also observed at the messenger RNA (mRNA) level. Time-course induction experiments showed that the effects of HGF on protein synthesis were delayed by about 48 to 72 hours, in contrast with the 12-hour lag found after IL-6 stimulation. Although the presence of glucocorticoids was not absolutely necessary for HGF to affect plasma protein synthesis, it moderately extended the effects. In pulse-chase experiments, it was found that the action of HGF was not due to an alteration of the rate of secretion of the proteins. The effects of HGF on the synthesis of albumin, transferrin, fibronectin, alpha1-antichymotrypsin, and haptoglobin could be counteracted by the simultaneous presence of IL-6 in the incubation media. A clear additive effect was observed only in the case of fibrinogen. No interaction was observed in the cases of CRP and AMG. The results of this study indicate that the effects of HGF on human hepatocytes may not simply be limited to its mitogenic activity, but that it also regulates hepatic-specific genes and antagonizes, in part, the action of IL-6.
Prospective Stage-Stratified Approach to AIDS-Related Kaposi's Sarcoma
Authors: Mark Bower, Alessia Dalla Pria, Chris Coyle, Eileen Andrews, Victoria Tittle, Sharanjit Dhoot, Mark Nelson
Journal: Journal of Clinical Oncology (2013)

Combination antiretroviral therapy (cART) is standard of care for patients with HIV diagnosed with Kaposi's sarcoma (KS), but the current role of systemic chemotherapy is undefined.Since 1998, a prospective stage-stratified approach has been adopted for 469 patients with HIV with KS. Patients with early-stage (T0) KS are treated with cART alone; patients with advanced-stage (T1) KS receive cART plus liposomal anthracycline chemotherapy. Clinical characteristics, overall survival, and KS progression-free survival were analyzed according to stage at presentation and treatment received.A total of 303 patients presented with T0 stage KS, including 237 who were not receiving cART, and 166 patients had T1 stage KS. Patients with T0 KS had higher CD4 cell counts (P < .001); 90% of patients with T0 KS who were not receiving cART and 84% of those with T1 KS were treated in accordance with the stage-stratified approach. Median follow-up was 4.6 years, and 5-year overall survival was 89%; 54 patients have died, 15 as a result of KS. Overall 5-year survival was 92% for T0 KS and 83% to T1 KS (P = .0024). On-treatment analysis of 213 cART-naive patients with T0 KS treated with cART alone revealed 5-year overall survival of 95% and progression-free survival of 77%. For 140 patients with T1 disease treated with cART and liposomal anthracycline chemotherapy, 5-year overall survival was 85%.This stage-stratified approach to the management of KS achieves high survival in patients with advanced KS and reduces exposure to chemotherapy in patients with early-stage KS.
Incidence of asthma and net change in symptoms in relation to changes in obesity
Authors: S. Chinn, S. H. Downs, J. M. Anto, M. W. Gerbase, B. Leynaert, R. de Marco, C. Janson, D. Jarvis, N. Künzli, J. Sunyer, C. Svanes, E. Zemp, U. Ackermann-Liebrich, P. Burney
Journal: European Respiratory Journal (2006)

The incidence of asthma has been reported to be associated with obesity. An alternative analysis, of net change in prevalence, does not require exclusion of those with asthma at baseline. Follow-up data were obtained from 9,552 participants in the European Community Respiratory Health Survey and the Swiss cohort Study on Air Pollution and Lung Disease in Adults. Incidence of asthma was analysed by proportional hazards regression, and net changes in symptoms and asthma status by generalised estimating equations, by obesity group. Incidence and net change in ever having had asthma were greater in females than in males, and in participants who remained obese compared with those who were never obese (hazard ratio 2.00, 95% confidence interval 1.25–3.20; excess net change 2.8%, 0.4–5.3% per 10 yrs). The effect of being obese on net change in diagnosed asthma was greater in females than in males, but for net change in wheeze without a cold it was greater in males. The present results are consistent with asthma being more frequently diagnosed in females, especially obese females. These findings may help to explain the reports of a stronger association between asthma and obesity in females than in males.
Effect of Glycine-Conjugated Bile Acids with and without Lecithin on Water and Glucose Absorption in Perfused Human Jejunum
Authors: David L. Wingate, Sidney F. Phillips, Alan F. Hofmann
Journal: Journal of Clinical Investigation (1973)

Perfusion studies were performed in healthy volunteers to test whether the secretory effect of conjugated bile acids, previously shown for the colon, was also present in the jejunum. A perfusion system with a proximal occlusive balloon (and continuous aspiration of duodenal secretions) was used; isotonic test solutions contained glycine-conjugated bile acids with or without lecithin. Fluid movement was measured by changes in the concentration of polyethylene glycol (PEG, mol wt 4,000). Conjugated dihydroxy bile acids inhibited electrolyte and fluid absorption and, at higher concentrations, evoked secretion of an isotonic fluid. Glucose absorption continued, despite fluid secretion, but its rate decreased. The secretory effects of bile acids were abolished by the addition of lecithin to the bile acid solutions. A trihydroxy bile acid (cholylglycine) had no effect on jejunal absorption. Small amounts (6-9%) of conjugated bile acids were absorbed in the jejunum; lecithin was well absorbed (72-90%). The results indicate that dihydroxy bile acids influence salt and water transport in the human jejunum but that this effect may be abolished when a polar lipid such as lecithin is present. We speculate that this effect of bile acids may modify fluid movement in the small intestine postprandially after fat absorption has occurred.
Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
Authors: Rajesh K. Thimmulappa, Hannah Lee, Tirumalai Rangasamy, Sekhar P. Reddy, Masayuki Yamamoto, Thomas W. Kensler, Shyam Biswal
Journal: Journal of Clinical Investigation (2006)

Host genetic factors that regulate innate immunity determine susceptibility to sepsis. Disruption of nuclear factor-erythroid 2–related factor 2 (Nrf2), a basic leucine zipper transcription factor that regulates redox balance and stress response, dramatically increased the mortality of mice in response to endotoxin- and cecal ligation and puncture–induced septic shock. LPS as well as TNF-α stimulus resulted in greater lung inflammation in Nrf2-deficient mice. Temporal analysis of pulmonary global gene expression after LPS challenge revealed augmented expression of large numbers of proinflammatory genes associated with the innate immune response at as early as 30 minutes in lungs of Nrf2-deficient mice, indicating severe immune dysregulation. The expression profile indicated that Nrf2 has a global influence on both MyD88-dependent and -independent signaling. Nrf2-deficient mouse embryonic fibroblasts showed greater activation of NF-κB and interferon regulatory factor 3 in response to LPS and polyinosinic-polycytidylic acid [poly(I:C)] stimulus, corroborating the effect of Nrf2 on MyD88-dependent and -independent signaling. Nrf2’s regulation of cellular glutathione and other antioxidants is critical for optimal NF-κB activation in response to LPS and TNF-α. Our study reveals Nrf2 as a novel modifier gene of sepsis that determines survival by mounting an appropriate innate immune response.
Early development of the metabolic syndrome after chemotherapy for testicular cancer
Authors: E.C. de Haas, R. Altena, H.M. Boezen, N. Zwart, A.J. Smit, S.J.L. Bakker, A.M. van Roon, A. Postma, B.H.R. Wolffenbuttel, H.J. Hoekstra, F.E. van Leeuwen, D.T. Sleijfer, J.A. Gietema
Journal: Annals of Oncology (2012)
CREST syndrome with pericardial but not peripheral calcinosis.
Authors: H.G. Taylor, P Sheldon, A.J. McCance, J.D. Skehan
Journal: Annals of the Rheumatic Diseases (1993)

Letters to the editor a two year history of recurrent painful violet erythema nodular lesions associated with high levels of RF (latex; range 1048-2000 U/ml).She denied asthenia, weight loss, fever, and had no respiratory or articular complaints.On physical examination many scattered, painful, tender and slightly raised violet subcutaneous nodules were found on the posterior aspects of both calves.The patient was afebrile.Results of cardiopulmonary and abdomipal explorations were unremarkable.White blood cell and platelet count were normal.The haemoglobin was 126 g/l and erythrocyte sedimentation rate 18 mm/lst h.Urea nitrogen, creatinine, glucose, bilirubin, aspartate transaminase, alkaline phosphatase, cholesterol, triglycerides, calcium, and phosphorus were all normal.A positive purified protein derivative skin test, antinuclear antibodies, cryoglobulins, and serum complement (C3 and C4) were unremarkable.Serum RF determined by turbidimetric immunoassay was 2048 U/ml (Quantex RF plus latex; WHO units).Rheumatoid factor determined by haemagglutination on slide (modified Waaler-Rose procedure) was 256 U/ml (Celarkit AR; Biokit SA, Spain; WHO units).Chest films showed a fibroproductive pattern affecting both upper lung lobes with- out paratracheal or perihiliary adenopathies.Microscopic examination of three sputum specimens stained by Ziehl-Neelsen's method disclosed no acid-fast bacilli.A wedge biopsy of one skin nodule was performed and pathological examination disclosed a granu- lomatous panniculitis consistent with erythema induratum (figure).Ziehl-Neelsen and auramine-rhodamine stains were negative.Sputum cultures in L6wenstein-Jensen medium grew M tuberculosis.Specific daily treatment with rifampicin 600 mg, isoniazid 300 mg, and pyrazinamide 1500 mg was started and continued for two months.Rifampicin and isoniazid was continued for four more months at the same dose.The two Mantoux tuberculin skin tests (5 tuberculin units of purified protein derivative) performed while the patient was receiving chemotherapy were negative.At the end of the first, third, and sixth months of treatment, RF had decreased to 600, 200, and 44-2 U/ml respectively.The patient remained asymptomatic, and skin lesions healed leaving a pigmented scar.Erythema induratum, included in the tuber- culids, is not a 'true' manifestation of skin tuberculosis because acid-fast bacilli are not Nodular panniculitis.Some granulomata show caseous central necrosis (haematoxylin and eosin).
Increased Rate of Sealing in Beating Heart Muscle of the Toad
Authors: W. C. DE MELLO, D. DEXTER
Journal: Circulation Research (1970)

The influence of stimulation on the healing-over of myocardial cells of the toad was investigated. The rate of sealing was markedly increased in beating muscles. This effect of stimulation on the healing process varied with the frequency of the stimulus and depended on the extracellular Ca concentration. Low sodium solutions increased the rate of sealing in stimulated muscles but not at rest. Some evidence is presented that the increased Ca influx which accompanies stimulation activates the reactions involved in the sealing process.