tbuckley/cabot-search huggingface dataset:
Audit of the outcome of peptic ulcer disease diagnosed 10 to 20 years previously.
Authors: J A Malliwah, M Tabaqchali, J Watson, C W Venables
Journal: Gut (1996)

METHODS/AIMS: During 1993-1994 an audit of the outcomes of a consecutive series of peptic ulcer patients, first diagnosed endoscopically between 1972-1983, was carried out. Three hundred and thirty six patients fitting the entry criteria were identified, 46 had died in the interval, and 44 were lost to follow up, leaving 246 available for evaluation. All patients completed questionnaires on their current symptomatic state, drug treatment, and details of any operations they had undergone since their original diagnosis. In addition they were asked to indicate, on an analogue scale, their overall assessment of how their ulcer problem was affecting them at the time of the review. Where available hospital records were obtained and analysed for any further admissions and the results of any further endoscopies. RESULTS: Of the 246 patients, 158 were men and 88 female. Duodenal ulcers (DU) were present in 204 and gastric ulcers (GU) in 51 (nine had both a DU and GU). Since the diagnosis 65 patients had undergone surgical treatment: 44 for poor ulcer control, nine for pyloric stenosis, nine for a perforation, one for a major gastrointestinal bleed, and two for a gastric carcinoma developing within two years of the diagnosis of a GU. The overall incidence of ulcer complications during this follow up period (excluding the carcinomas) was 7.7%. Initial medical treatment was with histamine H2 blockade in 234 patients--87.4% cimetidine (C) and 11% ranitidine (R)--with other agents in the remainder. At follow up 176 patients were still receiving medical treatment (C, 71%: R, 22%, other, 7%) including 30 who had previously undergone a definitive surgical procedure. Dyspeptic symptoms were recorded in 50.4% of the patients, abdominal pain being the commonest complaint. There was a significant relation between abdominal pain and the analogue scores provided by the patients with significantly more (p = 0.02) of those who had undergone surgical treatment recording this as a continuing problem (44.6% v 36%). CONCLUSION: There is no evidence provided by this study that, in these patients, their ulcer disease is undergoing spontaneous remission with time.
Phase I-II Trial of Prone Accelerated Intensity Modulated Radiation Therapy to the Breast to Optimally Spare Normal Tissue
Authors: Silvia C. Formenti, Daniela Gidea-Addeo, Judith D. Goldberg, Daniel F. Roses, Amber Guth, Barry S. Rosenstein, Keith J. DeWyngaert
Journal: Journal of Clinical Oncology (2007)

Purpose To report the clinical feasibility of a trial of accelerated whole-breast intensity modulated radiotherapy, with the patient in prone position, optimally to spare the heart and lung. Patients and Methods Patients with stages I or II breast cancer, excised by breast conserving surgery with negative margins, were eligible for this institutional review board–approved prospective trial. Computed tomography simulation was performed with the patient prone on a dedicated breast board, in the exact position used for treatment. A dose of 40.5 Gy, delivered at 2.7 Gy in 15 fractions, was prescribed to the index breast with an additional concomitant boost of 0.5 Gy delivered to the tumor bed, for a total dose of 48 Gy to the lumpectomy site. Physics constraints consisted of limiting ≤ 5% of the heart volume to receive ≥ 18 Gy and ≤ 10% of the ipsilateral lung volume to receive ≥ 20 Gy. Results Between September 2003 and August 2005, 91 patients were enrolled on the study. Median length of follow-up was 12 months (range, 1 to 28 months). In all patients the technique was feasible and heart and lung sparing was achieved as prescribed by the protocol. Acute toxicities consisting mostly of reversible grades 1-2 skin dermatitis (67%) and fatigue (18%) occurred in 75 patients. One patient sustained a regional recurrence rapidly followed by distant metastases. Conclusion Accelerated whole breast intensity modulated radiotherapy in the prone position is feasible and it permits a drastic reduction in the volume of lung and heart tissue exposed to significant radiation.
Excess Physical Limitations Among Adults With Diabetes in the U.S. Population, 1997–1999
Authors: Blythe Ryerson, Edward F. Tierney, Theodore J. Thompson, Michael M. Engelgau, Jing Wang, Edward W. Gregg, Linda S. Geiss
Journal: Diabetes Care (2003)

To estimate the prevalence of physical limitations associated with diabetes among U.S. adults > or =18 years of age.We conducted a cross-sectional analysis of the association between diabetes status and physical limitations using the 1997-1999 National Health Interview Survey (NHIS). Physical limitation was defined from self-reported degree of difficulty with nine tasks.People with diabetes had a higher proportion of any physical limitation than did people without diabetes overall (66 vs. 29%, P < 0.001), for both men (59 vs. 24%, P < 0.001) and women (72 vs. 34%, P < 0.001). Compared with those without diabetes, a higher proportion of people with diabetes had some physical limitation among all age groups, and the difference declined (all P < 0.001) with increasing age (46 vs. 18% for 18-44 years, 63 vs. 35% for 45-64 years, 74 vs. 53% for 65-74 years, and 85 vs. 70% for those 75 years and older). After controlling for demographic characteristics and several other confounders, the odds ratio of physical limitation among adults with diabetes versus those without diabetes was 1.9 (95% CI: 1.8-2.1).People with diabetes are much more likely to have a physical limitation than those without diabetes. Interventions are needed in this population to reduce progression from impairment to physical limitation and from physical limitation to disability, especially because the prevalence of diabetes is projected to increase dramatically in the next several decades.
Cyclophosphamide pulse therapy in idiopathic pulmonary fibrosis
Authors: M Kolb, J Kirschner, W Riedel, H Wirtz, M Schmidt
Journal: European Respiratory Journal (1998)

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with poor prognosis. Response to treatment is infrequent and the use of immunosuppressive agents other than corticosteroids is the subject of ongoing discussion because of uncertain efficacy and side-effects. To determine the efficacy and safety of cyclophosphamide pulse therapy in IPF, this study retrospectively analysed 18 patients with progressive IPF who were treated with intermittent i.v. cyclophosphamide (1-13 g x month(-1)) and additional oral prednisolone for 1 yr. Static lung volumes, arterial oxygen tension (Pa,O2) at rest, clinical symptoms and potential treatment-related side-effects were recorded. Cyclophosphamide had to be stopped in one patient, owing to repeated pulmonary infection; 11 patients were responders (five improving, six stabilizing) and six patients deteriorated. The change in vital capacity (VC) of responders was +6.7+/-18.0% (mean +/-SD), compared with -20.6+/-18.2% in nonresponders (p=0.008). Pa,O2 remained constant in responders (+0.13+/-0.88 kPa (+1.0+/-6.6 mmHg)), while it decreased in nonresponders (-2.08+/-1.92 kPa (-15.6+/-14.4 mmHg, p=0.008)). Additional prednisolone was reduced by 19.1+/-13.4 mg in responders, compared with 6.7+/-16.3 mg in nonresponders (p=0.02). VC at initiation of therapy was higher in responders (60.2+/-10.2 versus 40.3+/-12.9% predicted; p=0.004). No side-effects occurred, other than respiratory tract infection. These data demonstrate that intravenous cyclophosphamide pulse therapy may be a favourable regimen for certain patients with progressive idiopathic pulmonary fibrosis. Patients with a vital capacity of more than 50% predicted and a shorter duration of disease may benefit most.
ASN Policy on Managing Conflicts of Interest
Authors: John B. Stokes, Allison Haupt, Bruce A. Molitoris, Phillip Kokemueller, Tod Ibrahim
Journal: Journal of the American Society of Nephrology (2009)

The federal government, foundations, associations, and the Institute of Medicine (IOM) are examining the relationships between physicians and “commercial interests,” particularly biotechnology, medical device, and pharmaceutical companies (Table 1). Discovering a lack of “systematic information” about conflicts of interest (COI) and commercial bias, IOM recently recommended that the federal government study the effect of such conflicts “on the quality of medical research, education, and practice.”1

View this table:

Table 1. 
Recent activity concerning COI and commercial bias



The American Society of Nephrology (ASN) shares IOM's concern over the lack of data related to COI and agrees that more research is needed. However, even in the absence of concrete information, it is the responsibility of a professional society to try to understand the extent to which COI interface with its missions. Perhaps no single aspect of COI for societies and those who represent them is as visible and subject to scrutiny as continuing medical education (CME).

The longest phase of the educational continuum for physicians, CME is also a critical element of the country's health care system. “Given the accelerating pace of change in clinical information and technology, continuing education has never been more important,” observed the Josiah Macy, Jr., Foundation.2 By providing a preponderance of CME, professional societies such as ASN improve the quality of health care.3

In addition to CME, societies like ASN provide access to new knowledge by publishing peer-reviewed journals, support basic and clinical investigation through research grants, and advocate for the development of national health policies. To support these missions, many societies—including ASN—solicit funding from commercial interests.

Although some have argued that professional societies should begin to eliminate such funding, others have suggested that such a restriction “would marginalize critical roles that industry, and many physicians working in industry, play in critical medical research alliances.”3,4 …
Connective Tissue-Activating Peptide III: A Novel Blood Biomarker for Early Lung Cancer Detection
Authors: John Yee, Marianne D. Sadar, Don D. Sin, Michael Kuzyk, Li Xing, Jennifer Kondra, Annette McWilliams, S.F. Paul Man, Stephen Lam
Journal: Journal of Clinical Oncology (2009)

There are no reliable blood biomarkers to detect early lung cancer. We used a novel strategy that allows discovery of differentially present proteins against a complex and variable background.Mass spectrometry analyses of paired pulmonary venous-radial arterial blood from 16 lung cancer patients were applied to identify plasma proteins potentially derived from the tumor microenvironment. Two differentially expressed proteins were confirmed in 64 paired venous-arterial blood samples using an immunoassay. Twenty-eight pre- and postsurgical resection peripheral blood samples and two independent, blinded sets of plasma from 149 participants in a lung cancer screening study (49 lung cancers and 100 controls) and 266 participants from the National Heart Lung and Blood Institute Lung Health Study (45 lung cancer and 221 matched controls) determined the accuracy of the two protein markers to detect subclinical lung cancer.Connective tissue-activating peptide III (CTAP III)/ neutrophil activating protein-2 (NAP-2) and haptoglobin were identified to be significantly higher in venous than in arterial blood. CTAP III/NAP-2 levels decreased after tumor resection (P = .01). In two independent population cohorts, CTAP III/NAP-2 was significantly associated with lung cancer and improved the accuracy of a lung cancer risk prediction model that included age, smoking, lung function (FEV(1)), and an interaction term between FEV(1) and CTAP III/NAP-2 (area under the curve, 0.84; 95% CI, 0.77 to 0.91) compared to CAPIII/NAP-2 alone.We identified CTAP III/NAP-2 as a novel biomarker to detect preclinical lung cancer. The study underscores the importance of applying blood biomarkers as part of a multimodal lung cancer risk prediction model instead of as stand-alone tests.
Second-Line Therapies in Hepatocellular Carcinoma: Emergence of Resistance to Sorafenib
Authors: Augusto Villanueva, Josep M. Llovet
Journal: Clinical Cancer Research (2012)

Abstract Second-line therapies are needed for patients with advanced hepatocellular carcinoma who progress after sorafenib. Positive signals seen with brivanib in phase II studies, reported herein, have yet to be confirmed in phase III trials. Identification of the molecular mechanisms driving sorafenib resistance should guide drug development strategies in this setting. Clin Cancer Res; 18(7); 1824–6. ©2012 AACR.
The Growth and Metastasis of Human Hepatocellular Carcinoma Xenografts Are Inhibited by Small Interfering RNA Targeting to the Subunit ATP6L of Proton Pump
Authors: Xiaodong Lu, Wenxin Qin, Jinjun Li, Ning Tan, Dongning Pan, Haitao Zhang, Li Xie, Genfu Yao, Huiqun Shu, Ming Yao, Dafang Wan, Jianren Gu, Shengli Yang
Journal: Cancer Research (2005)

Abstract Extracellular pH is usually low in solid tumors, in contrast to the approximately neutral intracellular pH. V-ATPase, which overly functions in some cancers with metastatic potential, plays an important role in maintaining neutral cytosolic pH, very acidic luminal pH, and acidic extracellular pH. ATP6L, the 16 kDa subunit of proton pump V-ATPase, can provide proton hydrophilic transmembrane path. In this study, ATP6L in a human hepatocellular carcinoma cell line with highly metastatic potential (HCCLM3) was knocked down using DNA vector–based small interfering RNA (siRNA) to suppress the metastasis. The expression of ATP6L in stable siRNA transfectants, designated as si-HCCLM3 cells, was inhibited by ∼60%. The proton secretion and the intracellular pH recovery from NH4Cl-prepulsed acidification were inhibited in si-HCCLM3 cells. The invasion of the si-HCCLM3 cells was suppressed in vitro; simultaneously, the expressions of matrix metalloproteinase-2 and gelatinase activity were reduced. In vivo, at 35th day after implantation of the si-HCCLM3 xenografts into the livers in BalB/c (nu+/nu+) mice, the size of liver tumor tissues was dramatically smaller in siRNA group than in the controlled group. The most impressing effect of ATP6L siRNA is its striking reduction of the metastatic potential of HCCLM3 cells. In control, all eight mice had the intrahepatic metastasis and six of eight the pulmonary metastasis, whereas in ATP6L siRNA-treated group, three of eight had the intrahepatic metastasis and only one of eight the pulmonary metastasis. The results suggest that the inhibition of V-ATPase function via knockdown of ATP6L expression using RNA interfering technology can effectively retard the cancer growth and suppress the cancer metastasis by the decrease of proton extrusion and the down-regulation of gelatinase activity.
Physical exercise or micronutrient supplementation for the wellbeing of the frail elderly? A randomised controlled trial
Authors: M J M Chin A Paw, N de Jong, E G Schouten, W A van Staveren, F J Kok
Journal: British Journal of Sports Medicine (2002)

To examine the effects of 17 weeks of physical exercise and micronutrient supplementation on the psychological wellbeing of 139 independently living, frail, elderly subjects (inactive, body mass index < or =25 or experiencing weight loss).Participants (mean (SD) age 78.5 (5.7)) were randomly assigned to: (a) comprehensive, moderate intensity, group exercise; (b) daily micronutrient enriched foods (25-100% recommended daily amount); (c) both; (d) neither. A social programme and identical regular foods were offered as attention control and placebo.At baseline, moderate to low but significant correlations were found between general wellbeing scores and physical fitness (r = 0.28), functional performance (r = 0.37), and blood concentrations of pyridoxine (r = 0.20), folate (r = 0.25), and vitamin D (r = 0.23) (all p values < or =0.02), but not with physical activity levels and other blood vitamin concentrations. General wellbeing score and self rated health were not responsive to 17 weeks of exercise or nutritional intervention.Psychological wellbeing in frail elderly people was not responsive to 17 weeks of intervention with exercise and/or micronutrient enriched foods. The moderate but significant correlations between wellbeing and physical fitness and several blood vitamin concentrations at baseline suggest that changes in wellbeing may occur after long term interventions.
TCT-737 MONITORING THE LEARNING CURVE AND QUALITY OF CARE IN TAVI PROCEDURES BY CUSUM ANALYSIS
Authors: Alfredo Giuseppe Cerillo, Michele Murzi, Massimiliano Mariani, Federica Marchi, Stefano Maffei, Cataldo Palmieri, Mattia Glauber, Sergio Berti
Journal: Journal of the American College of Cardiology (2013)
Atrial natriuretic peptide suppresses compensatory renal growth in rats.
Authors: J L Logan, U F Michael
Journal: Journal of the American Society of Nephrology (1994)

Atrial natriuretic peptide (ANP) inhibits the growth of a variety of cell types in vitro including mesangial cells. The effects of ANP on the growth of the kidney in vivo were evaluated. A 2-h infusion of 0.2 microgram/250 g body wt per minute of ANP suppressed the subsequent uptake of [3H]thymidine into the renal DNA of uninephrectomized but not intact rats. This treatment also depressed the ratio of RNA/DNA in kidneys undergoing compensatory growth. Correlative physiologic studies revealed enhanced GFR in rats with two kidneys infused with ANP, but no increase in the GFR of uninephrectomized rats. It was concluded that ANP may oppose the growth factor(s) mediating compensatory renal growth.
Stat3 Inhibition Augments the Immunogenicity of B-cell Lymphoma Cells, Leading to Effective Antitumor Immunity
Authors: Fengdong Cheng, Hongwei Wang, Pedro Horna, Zi Wang, Bijal Shah, Eva Sahakian, Karrune V. Woan, Alejandro Villagra, Javier Pinilla-Ibarz, Said Sebti, Mitchell Smith, Jianguo Tao, Eduardo M. Sotomayor
Journal: Cancer Research (2012)

Abstract Mantle cell lymphoma (MCL) is an aggressive and incurable subtype of B-cell non–Hodgkin lymphomas. Although patients often respond initially to first-line treatment with chemotherapy plus monoclonal antibodies, relapse and decreased response to further lines of treatment eventually occurs. Harnessing the immune system to elicit its exquisite specificity and long-lasting protection might provide sustained MCL immunity that could potentially eradicate residual malignant cells responsible for disease relapse. Here, we show that genetic or pharmacologic disruption of Stat3 in malignant B cells augments their immunogenicity leading to better activation of antigen-specific CD4+ T cells and restoration of responsiveness of tolerized T cells. In addition, treatment of MCL-bearing mice with a specific Stat3 inhibitor resulted in decreased Stat3 phosphorylation in malignant B cells and anti-lymphoma immunity in vivo. Our findings therefore indicate that Stat3 inhibition may represent a therapeutic strategy to overcome tolerance to tumor antigens and elicit a strong immunity against MCL and other B-cell malignancies. Cancer Res; 72(17); 4440–8. ©2012 AACR.
Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand.
Authors: M A Bowen, D D Patel, X Li, B Modrell, A R Malacko, W C Wang, H Marquardt, M Neubauer, J M Pesando, U Francke
Journal: The Journal of Experimental Medicine (1995)

Antibody-blocking studies have demonstrated the role of CD6 in thymocyte-thymic epithelial (TE) cell adhesion. Here we report that CD6 expressed by COS cells mediates adhesion to TE cells and that this interaction is specifically blocked with an anti-CD6 monoclonal antibody (mAb) or with a mAb (J4-81) that recognized a TE cell antigen. We isolated and expressed a cDNA clone encoding this antigen and show that COS cells transfected with this cDNA bind a CD6 immunoglobulin fusion protein (CD6-Rg). This antigen, which we named ALCAM (activated leukocyte-cell adhesion molecule) because of its expression on activated leukocytes, appears to be the human homologue of the chicken neural adhesion molecule BEN/SC-1/DM-GRASP. The gene was mapped to human chromosome 3q13.1-q13.2 by fluorescence in situ hybridization of cDNA probes to metaphase chromosomes. We prepared an ALCAM-Rg fusion protein and showed that it binds to COS cell transfectants expressing CD6, demonstrating that ALCAM is a CD6 ligand. The observations that ALCAM is also expressed by activated leukocytes and that both ALCAM and CD6 are expressed in the brain suggest that ALCAM-CD6 interactions may play a role in the binding of T and B cells to activated leukocytes, as well as in interactions between cells of the nervous system.
Mechanisms of cell death induced by the suicide genes encoding purine nucleoside phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in vitro
Authors: Leonhard Mohr, Tim U. Krohne, Srinivas Shankara, Michael Geissler, Bruce Roberts, Jack R. Wands, Hubert E. Blum
Journal: Journal of Hepatology (2001)
Human immune response to immunization with a structurally defined polypeptide fragment of streptococcal M protein.
Authors: E H Beachey, G H Stollerman, R H Johnson, I Ofek, A L Bisno
Journal: The Journal of Experimental Medicine (1979)

We tested the ability of pepsin-extracted, highly purified M protein to induce type-specific immunity in experimental animals and humans. M protein was prepared from limited peptic digests of whole group A type 24 streptococci and was purified to chemical homogeneity as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, quantitative amino acid analysis, and Edman degradation. For vaccination, the lyophilized M24 protein preparation (pep M24) was precipitated in aluminum hydroxide. When injected into laboratory animals, alum-precipitated pep M24 produced type-specific protective antibodies and was free of non-type-specific immunoreactivity. In man, skin tests with 1-microgram doses of pep M24 were negative in all 37 adults tested. 12 adult human volunteers received two-four subcutaneous injections of 100-200 micrograms of alum-precipitated pep M24 at intervals of at least 2 wk. The immune response to pep M24 was measured by a variety of assays designed to detect (a) type-specific humoral antibodies (opsonophagocytic, long chain, and mouse protection tests); (b) total humoral antibodies (complement fixation and enzyme-linked immunosorbent assay); (c) cellular immunity (skin tests); and (d) heart cross-reactive antibodies (immunofluorescence). Type-specific opsonic antibodies developed in 10 of the 12 vaccinees, and positive delayed-type skin tests developed in 11. Immune sera from two of the vaccinees were effective in mouse-protection tests against challenge with M24 but not M6 streptococci. None of the volunteers developed heart-reactive antibodies or antibodies to non-type-specific M protein antigens. Alum-precipitated pep M24 was well-tolerated in man, and no serious local or systemic reactions were observed. Thus, pep M24 induces type-specific, protective antibodies in doses that are well-tolerated in man.