tbuckley/cabot-search huggingface dataset:
Fibroblast growth factor inducible 14 as potential target in patients with alcoholic hepatitis
Authors: Bernd Schnabl, David A Brenner
Journal: Gut (2012)

Alcoholic hepatitis is a distinct clinical entity characterised by jaundice and liver failure that generally occurs after decades of heavy alcohol use. Recovery from alcoholic hepatitis is determined by abstinence from alcohol, the presence of mild clinical symptoms and the implementation of appropriate therapy. Unfortunately, patients with severe alcoholic hepatitis have a high mortality rate of about 40% to 50% despite optimal medical management.1 A significant percentage of patients succumb to bacterial infections with infection-attributed mortality of 12% to 54%2 underscoring the importance of bacterial translocation and an impaired immune response. Moreover, patients with alcoholic hepatitis have a profound, often sepsis-like hyper-inflammatory state which suggests the possibility that proinflammatory mediators such as cytokines contribute to alcoholic hepatitis by promoting systemic inflammation and systemic inflammatory response syndrome.

Tumour necrosis factor α (TNFα) has been proposed to be the critical cytokine involved in the pathogenesis of alcoholic hepatitis, which is mostly based on animal models of experimental alcoholic liver disease.3 Inhibition of TNFα attenuates alcoholic liver injury in rats.4 Elevated plasma TNFα is a significant predictor of decreased long-term survival in patients with severe alcoholic hepatitis.5 However, clinical trials using an anti-TNFα strategy resulted in disappointing outcomes.6 ,7 In patients with moderate to severe alcoholic hepatitis, etanercept was associated …
Interferon gamma regulates antigen-induced eosinophil recruitment into the mouse airways by inhibiting the infiltration of CD4+ T cells.
Authors: I Iwamoto, H Nakajima, H Endo, S Yoshida
Journal: The Journal of Experimental Medicine (1993)

We have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4+ T cells and interleukin 5. To determine whether interferon gamma (IFN-gamma) regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of recombinant (r) murine IFN-gamma and of anti-IFN-gamma monoclonal antibody (mAb) on the eosinophil infiltration of the trachea induced by antigen inhalation in mice. The intraperitoneal administration of rIFN-gamma prevented antigen-induced eosinophil infiltration in the trachea of sensitized mice. The administration of rIFN-gamma also decreased antigen-induced CD4+ T cell but not CD8+ T cell infiltration in the trachea. On the other hand, pretreatment with anti-IFN-gamma mAb enhanced antigen-induced eosinophil and CD4+ T cell infiltration in the trachea. These results indicate that IFN-gamma regulates antigen-induced eosinophil recruitment into the tissue by inhibiting CD4+ T cell infiltration.
National Heart, Lung, and Blood Institute Workshop
Authors: Ivan M. Robbins, Timothy M. Moore, Carol J. Blaisdell, Steven H. Abman
Journal: Circulation (2012)

ecognizing the importance of improving lung health through lung disease research, the National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of multidisciplinary experts for the following purpose: (1) to review the current scientific knowledge underlying the basis for treatment of adults and children with pulmonary vascular diseases (PVDs); (2) to identify gaps, barriers, and emerging scientific opportunities in translational PVD research and the means to capitalize on these opportunities; (3) to prioritize new research directions that would be expected to affect the clinical course of PVDs; and (4) to make recommendations to the NHLBI on how to fill identified gaps in adult and pediatric PVD clinical research.Workshop participants reviewed experiences from previous PVD clinical trials and ongoing clinical research networks with other lung disorders, including acute respiratory distress syndrome, chronic obstructive lung disease, and idiopathic pulmonary fibrosis, as well.Bioinformatics experts discussed strategies for applying cutting-edge health information technology to clinical studies.Participants in the workshop considered approaches in the following broad concept areas: (1) improved phenotyping to identify potential subjects for appropriate PVD clinical studies;(2) identification of potential new end points for assessing key outcomes and developing better-designed PVD clinical trials; and (3) the establishment of priorities for specific clinical research needed to advance care of patients with various subsets of PVDs from childhood through adulthood.This report provides a summary of the objectives and recommendations to the NHLBI concentrating on clinical research efforts that are needed to better diagnose and treat PVDs.
Gastric cancer below the age of 55: implications for screening patients with uncomplicated dyspepsia
Authors: J Christie, N A Shepherd, B W Codling, R M Valori
Journal: Gut (1997)

Aims —To test the hypothesis that gastric cancer presenting with uncomplicated dyspepsia is rare below the age of 55. Patients and methods —The area studied was the postcode defined catchment area of a district general hospital (Gloucestershire Royal) serving a population of 280 500. An open access endoscopy service has been available in this district for more than 17 years. All cases of gastric cancer during a seven year period (1986–92) were drawn from the local pathology database. The database of the neighbouring hospital and the South West Cancer Registry were searched for missed cases from the postcoded area. Hospital and general practitioner records were retrospectively reviewed with respect to duration of symptoms, and previous consultation and investigation for dyspepsia; and alarming symptoms and signs suggestive of underlying malignancy (unexplained recent weight loss, dysphagia, haematemesis or melaena, anaemia, previous gastric surgery, palpable mass, and perforation). Results —Twenty five of 319 cases of gastric cancer detected during the seven year period were aged less than 55. Twenty four of these 25 patients presented with one or more suspicious symptoms or signs. Only one patient (4%) aged less than 55 presented with uncomplicated dyspepsia. In two patients there was a delay in diagnosis of more than six months after first presenting to the general practitioner. Both these patients had significant symptoms at presentation. Conclusion —Gastric cancer is rare below the age of 55 (7.8% of all cases) and, even in the presence of established open access endoscopy, presents with suspicious symptoms or signs in 96% of cases. The age limit for screening uncomplicated dyspepsia can be raised safely to 55.
Racial Differences in Survival From Breast Cancer
Authors: J. William Eley, Holly A. Hill, Vivien W. Chen, Donald F. Austin, Margaret N. Wesley, Hyman B. Muss, Raymond S. Greenberg, Ralph J. Coates, Pelayo Correa, Carol K. Redmond, Carrie P. Hunter, Allen A. Herman, Robert J Kurman, Robert Blacklow, Sam Shapiro, Brenda K. Edwards
Journal: JAMA (1994)

<h3>Objective.</h3> —To examine the ability of recognized prognostic factors for breast cancer to account for the observed poorer survival in blacks compared with their white counterparts. <h3>Design and Participants.</h3> —Subjects included 1130 women (612 blacks and 518 whites) aged 20 to 79 years residing in metropolitan Atlanta, Ga, New Orleans, La, or San Francisco/Oakland, Calif, who were diagnosed with primary invasive breast cancer. Information on stage, tumor characteristics, treatment, comorbid conditions, and sociodemographic factors was obtained from personal interview, physician and hospital records, and a pathology review of biopsy and surgical specimens. <h3>Main Outcome Measure.</h3> —Multivariable survival models were used to estimate the hazard ratio (relative risk of mortality) for blacks compared with whites, adjusting for various combinations of potential explanatory factors. <h3>Results.</h3> —After controlling for geographic site and age, the risk of dying was 2.2 times (95% confidence interval [CI], 1.8 to 2.8) greater for blacks than whites. Adjustment for stage reduced the risk from 2.2 to 1.7; further adjustment for sociodemographic variables had no effect. Treatment was not a contributing factor once stage and tumor pathology were in the model. After adjusting for stage, treatment, comorbid illness, and pathologic and sociodemographic variables, blacks continued to demonstrate a slightly increased, but not statistically significant, risk of death (hazard ratio=1.3; 95% CI, 1.0 to 1.8). Results were similar for all-cause mortality and breast cancer—specific mortality. <h3>Conclusions.</h3> —Approximately 75% of the racial difference in survival was explained by the prognostic factors studied. Sociodemographic variables appeared to act largely through racial differences in stage at diagnosis, which may be amenable to change through improved access to and use of screening for black women. (<i>JAMA</i>. 1994;272:947-954)
Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8
Authors: Melinda L Moseley, Tao Zu, Yoshio Ikeda, Wangcai Gao, Anne K Mosemiller, Randy S Daughters, Gang Chen, Marcy R Weatherspoon, H Brent Clark, Timothy J Ebner, John W Day, Laura P W Ranum
Journal: Nature Genetics (2006)
Molecular Pathways: Targeting RAC–p21-Activated Serine–Threonine Kinase Signaling in RAS-Driven Cancers
Authors: Nicole M. Baker, Hoi Yee Chow, Jonathan Chernoff, Channing J. Der
Journal: Clinical Cancer Research (2014)

Abstract Cancers driven by oncogenic Ras proteins encompass some of the most deadly human cancer types, and there is a pressing need to develop therapies for these diseases. Although recent studies suggest that mutant Ras proteins may yet be druggable, the most promising and advanced efforts involve inhibitors of Ras effector signaling. Most efforts to target Ras signaling have been aimed at the ERK mitogen-activated protein kinase and the phosphoinositide 3-kinase signaling networks. However, to date, no inhibitors of these Ras effector pathways have been effective against RAS-mutant cancers. This ineffectiveness is due, in part, to the involvement of additional effectors in Ras-dependent cancer growth, such as the Rac small GTPase and the p21-activated serine–threonine kinases (PAK). PAK proteins are involved in many survival, cell motility, and proliferative pathways in the cell and may present a viable new target in Ras-driven cancers. In this review, we address the role and therapeutic potential of Rac and group I PAK proteins in driving mutant Ras cancers. Clin Cancer Res; 20(18); 4740–6. ©2014 AACR.
Clinical features and<i><scp>WNT</scp>10A</i>mutations in seven unrelated cases of Schöpf–Schulz–Passarge syndrome
Authors: C. Tziotzios, G. Petrof, L. Liu, A. Verma, E.K. Wedgeworth, J.E. Mellerio, J.A. McGrath
Journal: British Journal of Dermatology (2014)

Schöpf‐Schulz‐Passarge syndrome (SSPS) is an autosomal recessive form of ectodermal dysplasia resulting from mutations in WNT10A. To document the spectrum of clinical features and search for pathogenic mutations in seven unrelated cases of SSPS. Clinical examination of patients and Sanger sequencing of genomic DNA spanning the coding exons and flanking spice sites of WNT10A. Most subjects had bilateral eyelid cysts and some degree of palmoplantar keratoderma, although nail, hair, and teeth abnormalities were variably present. Bi‐allelic pathogenic mutations in WNT10A were found in all seven subjects. New mutations comprised p.Glu390*, p.Ser270Arg, and p.Cys362Arg; the recurrent mutations were p.Cys107* and p.Ala131Thr. This study reveals the range of ectodermal pathology in cases of SSPS that result from WNT10A mutations. Eyelid cysts provide a useful clinical clue to diagnosing SSPS which may be less rare than is currently appreciated.
The Potential Predictive Value of Cyclooxygenase-2 Expression and Increased Risk of Gastrointestinal Hemorrhage in Advanced Non–Small Cell Lung Cancer Patients Treated with Erlotinib and Celecoxib
Authors: Mary J. Fidler, Athanassios Argiris, Jyoti D. Patel, David H. Johnson, Alan Sandler, Victoria M. Villaflor, John Coon, Lela Buckingham, Kelly Kaiser, Sanjib Basu, Philip Bonomi
Journal: Clinical Cancer Research (2008)

Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, potentiates antitumor effects of erlotinib in preclinical studies, and COX-2 is frequently expressed in non-small cell lung cancer (NSCLC). With these observations, we designed a phase II trial to evaluate the efficacy and safety of erlotinib plus celecoxib in advanced NSCLC.Previously treated stage IIIB/IV NSCLC patients were given celecoxib at 400 mg orally twice daily and erlotinib at 150 mg orally daily until disease progression. Planned accrual was 40 patients. Tissue was collected for epidermal growth factor receptor (EGFR) analysis and COX-2 immunohistochemistry.Twenty-six patients were enrolled (17 men, 9 women; median age, 66 years). Eighteen and 21 patients had tissue available for EGFR analysis and COX-2 immunohistochemistry, respectively. The median progression-free survival (PFS) and overall survival were 2.0 and 9.2 months, respectively. Eleven of 21 patients tested had increased tumor COX-2 expression, which was strongly associated with prolonged PFS (P=0.048). Four patients on anticoagulation or with a history of peptic ulcer disease had grade 3/grade 4 upper gastrointestinal bleeding (GIB), prompting early study closure. Three patients with GIB had endoscopy that found peptic ulcers.The combination of erlotinib and celecoxib does not seem superior to erlotinib alone in unselected patients. However, longer PFS with high-tumor COX-2 expression suggests that trials of EGFR and COX-2 inhibitors may be warranted in this patient subset. GIB observed in our trial supports excluding patients with a history of peptic ulcer disease or those requiring therapeutic anticoagulation from future EGFR and COX-2 inhibitor studies.
Improper Insulin Compliance May Lead to Hepatomegaly and Elevated Hepatic Enzymes in Type 1 Diabetic Patients
Authors: Y. Miles Yu, Campbell P. Howard
Journal: Diabetes Care (2004)

We have encountered hepatomegaly and pronounced elevation of liver enzymes AST and ALT in four patients with type 1 diabetes. These patients shared similar clinical features. They were all female (aged 11–14 years) with poor glycemic control. All had frequent hyperglycemia and intermittent hypoglycemia related to their history of poor compliance. Most of them had multiple hospital admissions for severe hyperglycemia and/or diabetic ketoacidosis. In addition to their high daily doses of insulin (1.3–2.2 units · kg−1 · day−1), most were receiving extra doses of insulin to correct their frequent hyperglycemia. A1C levels were all higher than normal (ranging from 9.2 to 14.5%). Their initial AST and ALT levels were at least 30- and 14-fold higher than the normal limits, respectively, but the other liver function tests, such as alkaline phosphatase, prothrombin/partial prothrombintime, and total bilirubin, were normal except for one …
Efficacy of Coronary Stenting Versus Balloon Angioplasty in Small Coronary Arteries
Authors: Michael P. Savage, David L. Fischman, Randal Rake, Martin B. Leon, Richard A. Schatz, Ian Penn, Masakiyo Nobuyoshi, Jeffrey Moses, John Hirshfeld, Richard Heuser, Donald Baim, Michael Cleman, Jeffrey Brinker, Sharon Gebhardt, Sheldon Goldberg
Journal: Journal of the American College of Cardiology (1998)

Objectives. The goal of this study was to compare the efficacy of elective stent implantation and balloon angioplasty for new lesions in small coronary arteries. Background. Palmaz-Schatz stents have been designed and approved by the Food and Drug Administration for use in coronary arteries with diameters ≥3.0 mm. The efficacy of elective stent placement in smaller vessels has not been determined. Methods. By quantitative coronary angiography, 331 patients in the Stent Restenosis Study (STRESS) I–II were determined to have a reference vessel <3.0 mm in diameter. Of these, 163 patients were randomly assigned to stenting (mean diameter 2.69 ± 0.21 mm), and 168 patients were assigned to angioplasty (mean diameter 2.64 ± 0.24 mm). The primary end point was restenosis, defined as ≥50% diameter stenosis at 6-month follow-up angiography. Clinical event rates at 1 year were assessed. Results. Baseline clinical and angiographic characteristics were similar in the two groups. Procedural success was achieved in 100% of patients assigned to stenting and in 92% of patients assigned to angioplasty (p < 0.001). Abrupt closure within 30 days occurred in 3.6% of patients in both groups. Compared with angioplasty, stenting conferred a significantly larger postprocedural lumen diameter (2.26 vs. 1.80 mm, p < 0.001) and a larger lumen at 6 months (1.54 vs. 1.27 mm, p < 0.001). Restenosis (≥50% diameter stenosis at follow-up) occurred in 34% of patients assigned to stenting and in 55% of patients assigned to angioplasty (p < 0.001). At 1 year, event-free survival was achieved in 78% of the stent group and in 67% of the angioplasty group (p = 0.019). Conclusions. These findings suggest that elective stent placement provides superior angiographic and clinical outcomes than balloon angioplasty in vessels slightly smaller than 3 mm.
Emergence of a <i>BCR-ABL</i> Translocation in a Patient With the <i>JAK2</i>V617F Mutation: Evidence for Secondary Acquisition of <i>BCR-ABL</i> in the <i>JAK2</i>V617F Clone
Authors: Osamu Yamada, Emna Mahfoudhi, Isabelle Plo, Kohji Ozaki, Mayuka Nakatake, Masaharu Akiyama, Hisashi Yamada, Kiyotaka Kawauchi, William Vainchenker
Journal: Journal of Clinical Oncology (2014)
Effectiveness of a Quality Improvement Intervention for Adolescent Depression in Primary Care Clinics
Authors: Joan Rosenbaum Asarnow, Lisa H. Jaycox, Naihua Duan, Anne P. LaBorde, Margaret M. Rea, Pamela Murray, Martin Anderson, Christopher Landon, Lingqi Tang, Kenneth B. Wells
Journal: JAMA (2005)

Depression is a common condition associated with significant morbidity in adolescents. Few depressed adolescents receive effective treatment for depression in primary care settings.To evaluate the effectiveness of a quality improvement intervention aimed at increasing access to evidence-based treatments for depression (particularly cognitive-behavior therapy and antidepressant medication), relative to usual care, among adolescents in primary care practices.Randomized controlled trial conducted between 1999 and 2003 enrolling 418 primary care patients with current depressive symptoms, aged 13 through 21 years, from 5 health care organizations purposively selected to include managed care, public sector, and academic medical center clinics in the United States.Usual care (n = 207) or 6-month quality improvement intervention (n = 211) including expert leader teams at each site, care managers who supported primary care clinicians in evaluating and managing patients' depression, training for care managers in manualized cognitive-behavior therapy for depression, and patient and clinician choice regarding treatment modality. Participating clinicians also received education regarding depression evaluation, management, and pharmacological and psychosocial treatment.Depressive symptoms assessed by Center for Epidemiological Studies-Depression Scale (CES-D) score. Secondary outcomes were mental health-related quality of life assessed by Mental Health Summary Score (MCS-12) and satisfaction with mental health care assessed using a 5-point scale.Six months after baseline assessments, intervention patients, compared with usual care patients, reported significantly fewer depressive symptoms (mean [SD] CES-D scores, 19.0 [11.9] vs 21.4 [13.1]; P = .02), higher mental health-related quality of life (mean [SD] MCS-12 scores, 44.6 [11.3] vs 42.8 [12.9]; P = .03), and greater satisfaction with mental health care (mean [SD] scores, 3.8 [0.9] vs 3.5 [1.0]; P = .004). Intervention patients also reported significantly higher rates of mental health care (32.1% vs 17.2%, P<.001) and psychotherapy or counseling (32.0% vs 21.2%, P = .007).A 6-month quality improvement intervention aimed at improving access to evidence-based depression treatments through primary care was significantly more effective than usual care for depressed adolescents from diverse primary care practices. The greater uptake of counseling vs medication under the intervention reinforces the importance of practice interventions that include resources to enable evidence-based psychotherapy for depressed adolescents.
Quality of Life and Sexual Functioning in Cervical Cancer Survivors
Authors: Michael Frumovitz, Charlotte C. Sun, Leslie R. Schover, Mark F. Munsell, Anuja Jhingran, J. Taylor Wharton, Patricia Eifel, Therese B. Bevers, Charles F. Levenback, David M. Gershenson, Diane C. Bodurka
Journal: Journal of Clinical Oncology (2005)

Purpose To compare quality of life and sexual functioning in cervical cancer survivors treated with either radical hysterectomy and lymph node dissection or radiotherapy. Methods Women were interviewed at least 5 years after initial treatment for cervical cancer. Eligible women had squamous cell tumors smaller than 6 cm at diagnosis, were currently disease-free, and had either undergone surgery or radiotherapy, but not both. The two treatment groups were then compared using univariate analysis and multivariate linear regression with a control group of age- and race-matched women with no history of cancer. Results One hundred fourteen patients (37 surgery, 37 radiotherapy, 40 controls) were included for analysis. When compared with surgery patients and controls using univariate analysis, radiation patients had significantly poorer scores on standardized questionnaires measuring health-related quality of life (physical and mental health), psychosocial distress and sexual functioning. The disparity in sexual function remained significant in a multivariate analysis. Univariate and multivariate analyses did not show significant differences between radical hysterectomy patients and controls on any of the outcome measures. Conclusion Cervical cancer survivors treated with radiotherapy had worse sexual functioning than did those treated with radical hysterectomy and lymph node dissection. In contrast, these data suggest that cervical cancer survivors treated with surgery alone can expect overall quality of life and sexual function not unlike that of peers without a history of cancer.
Topical clindamycin phosphate compared with oral tetracycline in the treatment of acne vulgaris
Authors: A. KATSAMBAS, A.A. TOWARKY, J. STRATIGOS
Journal: British Journal of Dermatology (1987)

Journal Article Topical clindamycin phosphate compared with oral tetracycline in the treatment of acne vulgaris Get access A. KATSAMBAS, A. KATSAMBAS A.Syngros, Hospital, Athens, Greece A.Katsambas, A.Syngros Hospital, 5 Dragoumi Sir., 16121 Kessariani, Athens, Greece. Search for other works by this author on: Oxford Academic Google Scholar A.A. TOWARKY, A.A. TOWARKY A.Syngros, Hospital, Athens, Greece Search for other works by this author on: Oxford Academic Google Scholar J. STRATIGOS J. STRATIGOS A.Syngros, Hospital, Athens, Greece Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 116, Issue 3, 1 March 1987, Pages 387–391, https://doi.org/10.1111/j.1365-2133.1987.tb05853.x Published: 01 March 1987