tbuckley/cabot-search huggingface dataset:
Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group.
Authors: J Rosenstock, G Park, J Zimmerman
Journal: Diabetes Care (2000)

OBJECTIVE: Insulin glargine (HOE 901, 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human insulin) is a novel recombinant analog of human insulin with a shift in the isoelectric point producing a retarded absorption rate and an increased duration of action that closely mimics normal basal insulin secretion. It recently received approval from the Food and Drug Administration. The aim of this study was to evaluate 2 formulations of insulin glargine for safety and efficacy in the treatment of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 4-week trial, 256 patients with type 1 diabetes received either NPH insulin or insulin glargine containing 30 microg/ml zinc (insulin glargine[30]) or 80 microg/ml zinc (insulin glargine[80]). Insulin glargine was given subcutaneously once daily at bedtime. NPH insulin was given either once daily (at bedtime) or twice daily (before breakfast and at bedtime), according to the patient's prestudy regimen. The initial doses of insulin glargine and NPH were based on the previous NPH total daily dose. RESULTS: At study end point, insulin glargine-pooled groups had significantly lower fasting plasma glucose (FPG) levels than the NPH insulin group, with adjusted mean FPG levels reduced by 2.2 mmol/l (P = 0.0001). Insulin glargine was superior to NPH insulin in reducing FPG levels in patients who had previously received NPH insulin twice daily but not in patients who had previously received NPH once daily. FPG levels were more stable in patients using insulin glargine than in patients using NPH insulin. A subset of patients (n = 71) underwent hourly overnight plasma glucose measurements. Insulin glargine patients exhibited lower FPG levels after 5:00 A.M.; the difference was significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30] was 7.8 mmol/l; for insulin glargine[80], 7.3 mmol/l; and for NPH, 10.7 mmol/l. Both formulations of insulin glargine were well tolerated, similar to NPH insulin. CONCLUSIONS: Basal insulin glargine administered once daily for 4 weeks as part of a basal-bolus multiple daily insulin regimen was safe and more effective in lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes.
Stimulation of the Dopamine 1 Receptor Increases Lung Edema Clearance
Authors: MICHELE L. BARNARD, KAREN M. RIDGE, FERNANDO SALDIAS, ELIOT FRIEDMAN, MEIR GARE, CARMEN GUERRERO, EMILIA LECUONA, ALEJANDRO M. BERTORELLO, ADRIAN I. KATZ, JACOB I. SZNAJDER
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We previously reported that lung edema clearance was stimulated by dopamine (DA). The purpose of this study was to determine whether the DA-mediated stimulation of edema clearance occurs via an adrenergic or dopaminergic regulation of alveolar epithelial Na,K-ATPase. When isolated perfused rat lungs were coinstilled with DA and SCH 23390 (a specific D1 receptor antagonist), there was a dose-dependent attenuation of the stimulatory effects of DA. Coinstillation with S-sulpiride (a specific D2 receptor antagonist) or propranolol (a β -adrenergic antagonist) did not alter DA-stimulated clearance. Similarly, the specific dopaminergic D1 agonist fenoldopam increased lung edema clearance, but quinpirole (a specific dopaminergic D2 agonist) did not. 125I-SCH 23982 binding studies suggested that D1 receptors are expressed on alveolar type II (ATII) cells with an apparent dissociation constant (K d) of 4.4 nM and binding maximum (Bmax) 9.8 pmol/mg. Consistent with these results, the D1 receptor messenger RNA (mRNA) and protein were detected in ATII cells by reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. These data demonstrate a novel mechanism involving the activation of dopaminergic D1 receptors which mediates DA-stimulated edema removal from rat lungs.
The IL-18 Antagonist IL-18–Binding Protein Is Produced in the Human Ovarian Cancer Microenvironment
Authors: Grazia Carbotti, Gaia Barisione, Anna Maria Orengo, Antonella Brizzolara, Irma Airoldi, Marina Bagnoli, Patrizia Pinciroli, Delia Mezzanzanica, Maria Grazia Centurioni, Marina Fabbi, Silvano Ferrini
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Interleukin (IL)-18 is an immune-enhancing cytokine, which induces IFN-γ production, T-helper 1 responses, and antitumor effects. In turn, IFN-γ stimulates IL-18–binding protein production, which blocks IL-18 activity. In view of the potential use of IL-18 in epithelial ovarian cancer (EOC) immunotherapy, here, we studied IL-18BP expression and its regulation by cytokines in EOC cells in vitro and in vivo. Experimental Design: Expression and production of IL-18BP in EOC cell lines, primary ovarian carcinomas, and the corresponding normal tissues, patients' serum, and ascites were investigated by immunochemistry, ELISA, screening of gene expression profiles, and reverse-transcription PCR. Results: Analysis of gene expression profiles revealed that IL18BP mRNA is increased in EOC tumors compared with normal ovary cells. Release of IL-18BP was detectable in EOC sera and to a greater extent in the ascites, indicating production at the tumor site. Indeed, immunochemical analyses on cells isolated from the ascites and on tumor sections indicated that IL-18BP is expressed in both tumor cells and tumor-associated leukocytes, which displayed a CD3−CD20−NKp46−CD13+CD14low phenotype. EOC cell lines do not constitutively express IL-18BP. However, its release is inducible both by IFN-γ stimulation in vitro and by xenotransplantation of EOC cells in immune-deficient mice, suggesting a role for the microenvironment. In vitro experiments and immunochemistry indicated that IL-27 is also involved in IL-18BP upregulation in EOC cell lines and primary cells through STAT1 activation. Together, these data indicate that IL-18BP, which is produced in EOC in response to microenvironmental factors, may inhibit endogenous or exogenous IL-18 activity. Clin Cancer Res; 19(17); 4611–20. ©2013 AACR.
Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section
Authors: Hedvig E Jakobsson, Thomas R Abrahamsson, Maria C Jenmalm, Keith Harris, Christopher Quince, Cecilia Jernberg, Bengt Björkstén, Lars Engstrand, Anders F Andersson
Journal: Gut (2013)

<h3>Objective</h3> The early intestinal microbiota exerts important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response. <h3>Design</h3> The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months. <h3>Results</h3> Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood. <h3>Conclusions</h3> CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.
Renal intracortical blood flow distribution, function, and sodium excretion in unanesthetized dogs following vena caval ligation.
Authors: R A Gutman, R L McRae
Journal: Circulation Research (1975)

We studied the renal function and the intrarenal blood flow of nine dogs whose thoracic inferior vena cava had been previously ligated (caval dogs) and nine other dogs. Following preparative surgery which included placement of a left atrial catheter, a femoral artery catheter, and bilateral ureteral catheters, the caval dogs gained an average of 2.1 kg of fluid weight, whereas the normal dogs gained no weight. Although neither the caval dogs' blood pressure (114 plus or minus 7 vs 120 plus or minus 4 mm Hg) nor their inulin clearance (0.64 plus or minus 0.06 vs. 0.79 plus or minus 0.06 ml/min g-1 kidney weight) was significantly reduced, their estimated renal blood flow (Cpah/[1-hematocrit]) was considerably lower (2.30 plus or minus 0.24 vs. 3.25 plus or minus 0.15 ml/min g-1). During the clearance study, the caval dogs' excretion of sodium (79 plus or minus 18 vs. 158 plus or minus 17 muEq/min) and their fractional clearance of sodium (2.0 plus or minus 0.4 vs. 3.4 plus or minus 0.5%) were reduced. Studies with microspheres failed to demonstrate a selective decrease in blood flow. However, comparison studies of nine other dogs (five caval and four normal) demonstrated that microsphere results were less reproducible in caval dogs than they were in normal dogs. We have concluded taht reduced blood flow is the only consistent alteration of renal function in this edematous animal model and that previous suggestions of altered distribution are not supported by these studies.
Meeting the Decision-Making Preferences of Patients With Breast Cancer in Oncology Consultations: Impact on Decision-Related Outcomes
Authors: Richard Brown, Phyllis Butow, Maureen Wilson-Genderson, Juerg Bernhard, Karin Ribi, Ilona Juraskova
Journal: Journal of Clinical Oncology (2012)

To investigate how involvement preferences of patients with breast cancer change during the treatment decision-making process and determine the impact of meeting patients' expectations on decision-making outcomes.Participants were 683 patients with breast cancer from 62 oncologists in five different countries recruited to an International Breast Cancer Study Group (IBCSG 33-03) project. Questionnaires elicited patients' pre- and postconsultation preferences for involvement in treatment decision making and whether these were met or not. Decision-related outcomes were assessed postconsultation.Before the consultation, most patients preferred shared or patient-directed treatment decision making. After the consultation, 43% of patients' preferences changed, and most shifted toward patient-directed decisions. The actual postconsultation decision was more likely to be made according to postconsultation rather than preconsultation preferences. Compared with patients who were less involved than they had hoped to be, patients who were as involved as they had hoped to be or were even more involved in decision making had significantly better decision-related outcomes. This was true regardless of whether preference change occurred.Many patients with early-stage breast cancer have treatment options and approach treatment decisions with a desire for decisional control, which may increase after their consultation. Patients' ultimate involvement preferences were more likely to be consistent with the way the decision was actually made, suggesting that patients need to feel concordance between their preference and the actual decision. Patients who directed decisions, even if more than they hoped for, fared better on all decision-related outcomes. These results emphasize the need for oncologists to endorse and facilitate patient participation in treatment decision making.
Association of human T lymphotropic virus type I with Sjögren syndrome: Table 1
Authors: Ayumi Hida, Misa Imaizumi, Nobuko Sera, Masazumi Akahoshi, Midori Soda, Renju Maeda, Eiji Nakashima, Hideki Nakamura, Hiroaki Ida, Atsushi Kawakami, Katsumi Eguchi
Journal: Annals of the Rheumatic Diseases (2010)

<h3></h3> Individuals living with chronic health conditions are often advised to adopt healthier lifestyles, including improving their nutrition. What is often disregarded by health professionals is that information-giving is often insufficient in supporting maintainable, substantial changes. Making long-term alterations to one9s lifestyle is challenging regardless of one9s circumstances. However, in the context of managing a chronic health condition one is faced with psychological barriers of a specific kind. Individuals with chronic health conditions may dislike being reminded of their physical difficulties, but adhering to a new 9healthier9 schedule means that one remains vigilant of daily choices and is consequently more aware of the underlying health condition. This awareness may result in undesirable emotional states such as sadness or anxiety that one might find difficult to handle. In an effort to then avoid, deny, or numb oneself from the worries or reminders of the chronic illness, it may become increasingly difficult to maintain a healthier lifestyle. The presentation will introduce mindfulness techniques for identifying and better handling undesirable thoughts, emotions and physical sensations that may act as barriers to healthier lifestyles. It will also discuss ways for initiating and maintaining internally motivated lifestyle changes though the activation of one9s personal values rather than acting on mandates of others such as family members or health professionals. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6127
American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility
Authors: Mark E. Robson, Angela R. Bradbury, Banu Arun, Susan M. Domchek, James M. Ford, Heather L. Hampel, Stephen M. Lipkin, Sapna Syngal, Dana S. Wollins, Noralane M. Lindor
Journal: Journal of Clinical Oncology (2015)

The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services.
Electrophysiological Characteristics of Septal Hypertrophy in Patients With Hypertrophic Obstructive Cardiomyopathy and Moderate to Severe Symptoms
Authors: Burghard Schumacher, Frank H. Gietzen, Hans Neuser, Joachim Schümmelfeder, Michael Schneider, Sebastian Kerber, Rainer Schimpf, Christian Wolpert, Martin Borggrefe
Journal: Circulation (2005)

In hypertrophic obstructive cardiomyopathy, regional hypertrophy, myocardial replacement scarring, expanded interstitial fibrosis, and myocardial disarray can be found. The electrophysiological consequences of this substrate have not yet been investigated. Thus, the aim of this study was to assess the local electrophysiological characteristics of regional left ventricular (LV) septal hypertrophy. In 9 patients with hypertrophic obstructive cardiomyopathy, electroanatomic voltage mapping of the LV was performed during sinus rhythm to determine the regional voltage amplitude. In addition, the morphology of the regional bipolar endocardial electrogram was assessed. During multisite LV stimulation, the stimulus-to-V intervals in both septal hypertrophy and the lateral LV myocardium were determined. Bipolar electroanatomic voltage mapping revealed a significant reduction in regional voltage amplitude in septal hypertrophic areas compared with lateral LV areas without evidence of hypertrophy (0.41+/-0.24 versus 13.5+/-1.85 mV; P<0,001). Local bipolar electrogram analysis demonstrated fractionated and prolonged endocardial potentials in septal hypertrophic areas (with split potentials present in 6 patients) that were not revealed at lateral myocardial sites (110.1+/-24.6 versus 80.1+/-6.6 ms; P=0.005). The stimulus-to-V interval was significantly longer (62.9+/-10.3 versus 24.1+/-9.1 ms; P=0.005) in septal hypertrophic areas compared with the lateral LV. In LV regions with extensive hypertrophy, a marked reduction of bipolar voltage amplitude can be found, as well as local conduction delay and conduction block. This result is consistent with the findings of regional myocardial scarring and may contribute to the increased incidence of ventricular tachyarrhythmias in patients with hypertrophic obstructive cardiomyopathy.
Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity
Authors: HJ Broxterman, P Sonneveld, N Feller, GJ Ossenkoppele, DC Wahrer, CA Eekman, M Schoester, J Lankelma, HM Pinedo, B Lowenberg, GJ Schuurhuis
Journal: Blood (1996)
The Impact of Renal Function on Outcomes of Bariatric Surgery
Authors: Nicole A. Turgeon, Sebastian Perez, Max Mondestin, S. Scott Davis, Edward Lin, Sudha Tata, Allan D. Kirk, Christian P. Larsen, Thomas C. Pearson, John F. Sweeney
Journal: Journal of the American Society of Nephrology (2012)

The effect of CKD on the risks of bariatric surgery is not well understood. Using the American College of Surgeons National Surgical Quality Improvement Program Participant Use File, we analyzed 27,736 patients who underwent bariatric surgery from 2006 through 2008. Before surgery, 34 (0.12%) patients were undergoing long-term dialysis. Among those not undergoing dialysis, 20,806 patients (75.0%) had a normal estimated GFR or stage 1 CKD, 5011 (18.07%) had stage 2 CKD, 1734 (6.25%) had stage 3 CKD, 94 (0.34%) had stage 4 CKD, and 91 (0.33%) had stage 5 CKD. In an unadjusted analysis, CKD stage was directly associated with complication rate, ranging from 4.6% for those with stage 1 CKD or normal estimated GFR to 9.9% for those with stage 5 CKD (test for trend, P<0.001). Multivariable logistic regression demonstrated that CKD stage predicts higher complication rates (odds ratio for each higher CKD stage, 1.30) after adjustment for diabetes and hypertension. Although patients with higher CKD stage had higher complication rates, the absolute incidence of complications remained <10%. In conclusion, these data demonstrate higher risks of bariatric surgery among patients with worse renal function, but whether the potential benefits outweigh the risks in this population requires further study.
Embryonic Stem Cell–Derived Dendritic Cells Expressing Glypican-3, a Recently Identified Oncofetal Antigen, Induce Protective Immunity against Highly Metastatic Mouse Melanoma, B16-F10
Authors: Yutaka Motomura, Satoru Senju, Tetsuya Nakatsura, Hidetake Matsuyoshi, Shinya Hirata, Mikio Monji, Hiroyuki Komori, Daiki Fukuma, Hideo Baba, Yasuharu Nishimura
Journal: Cancer Research (2006)

Abstract We have recently established a method to generate dendritic cells from mouse embryonic stem cells. By introducing exogenous genes into embryonic stem cells and subsequently inducing differentiation to dendritic cells (ES-DC), we can now readily generate transfectant ES-DC expressing the transgenes. A previous study revealed that the transfer of genetically modified ES-DC expressing a model antigen, ovalbumin, protected the recipient mice from a challenge with an ovalbumin-expressing tumor. In the present study, we examined the capacity of ES-DC expressing mouse homologue of human glypican-3, a recently identified oncofetal antigen expressed in human melanoma and hepatocellular carcinoma, to elicit protective immunity against glypican-3-expressing mouse tumors. CTLs specific to multiple glypican-3 epitopes were primed by the in vivo transfer of glypican-3-transfectant ES-DC (ES-DC-GPC3). The transfer of ES-DC-GPC3 protected the recipient mice from subsequent challenge with B16-F10 melanoma, naturally expressing glypican-3, and with glypican-3-transfectant MCA205 sarcoma. The treatment with ES-DC-GPC3 was also highly effective against i.v. injected B16-F10. No harmful side effects, such as autoimmunity, were observed for these treatments. The depletion experiments and immunohistochemical analyses suggest that both CD8+ and CD4+ T cells contributed to the observed antitumor effect. In conclusion, the usefulness of glypican-3 as a target antigen for antimelanoma immunotherapy was thus shown in the mouse model using the ES-DC system. Human dendritic cells expressing glypican-3 would be a promising means for therapy of melanoma and hepatocellular carcinoma. (Cancer Res 2006; 66(4): 2414-22)
Statistical reappraisal of the clinical significance of nail beading in rheumatoid arthritis.
Authors: E N Grant, N Bellamy, W W Buchanan, E M Grace, S O'Leary
Journal: Annals of the Rheumatic Diseases (1985)

Nail beading has previously been reported as an accompaniment of rheumatoid arthritis. In order to assess the clinical significance of this form of nychodystrophy the fingernails and toenails of 119 patients with rheumatoid arthritis and an equal number of control subjects were studied. Analysis of data based on 4642 nails indicates that the presence of a global pattern of beading (i.e. greater than or equal to 50% involvement of the nail area) on the surface of at least six fingernails or four toenails is highly suggestive of underlying rheumatoid disease. The positive predictive value of these configurations is in the order of 95%. Nail beading, however, is infrequent in early disease and therefore its diagnostic value is limited. Although there is a strong association between nail beading and rheumatoid arthritis, the aetiology and prognostic implications of this clinical sign remain obscure.