tbuckley/cabot-search huggingface dataset:
Effect of acarbose on insulin sensitivity in elderly patients with diabetes.
Authors: G S Meneilly, E A Ryan, J Radziuk, D C Lau, J F Yale, J Morais, J L Chiasson, R Rabasa-Lhoret, P Maheux, D Tessier, T Wolever, R G Josse, D Elahi
Journal: Diabetes Care (2000)

OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on insulin release and insulin sensitivity in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for 12 months. Before and after randomization, subjects underwent a meal tolerance test and a hyperglycemic glucose clamp study designed to measure insulin release and sensitivity. RESULTS: After 12 months of therapy there was a significant difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5 +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P &amp;lt; 0.05) and in incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l, placebo vs. acarbose group, P &amp;lt; 0.001) between groups. There was a significant difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2 vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P &amp;lt; 0.01). The change in fasting insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs. acarbose group, P &amp;lt; 0.05) and incremental postprandial insulin responses (-89 +/- 26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P &amp;lt; 0.01) was also significantly different between groups. During the hyperglycemic clamps, glucose and insulin values were similar in both groups before and after therapy However, there was a significant difference in the change in insulin sensitivity in response to treatment between the placebo and the acarbose groups (0.001 +/- 0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P &amp;lt; 0.05) CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in elderly patients with diabetes.
Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial
Authors: M William Audeh, James Carmichael, Richard T Penson, Michael Friedlander, Bethan Powell, Katherine M Bell-McGuinn, Clare Scott, Jeffrey N Weitzel, Ana Oaknin, Niklas Loman, Karen Lu, Rita K Schmutzler, Ursula Matulonis, Mark Wickens, Andrew Tutt
Journal: The Lancet (2010)
Exogenous nitric oxide inhibits apoptosis in guinea pig gastric mucous cells
Authors: C L Potter
Journal: Gut (2000)

<h3>BACKGROUND</h3> Increased nitric oxide (NO) synthase activity and enhanced apoptosis are features of gastric mucosa infected with <i>Helicobacter pylori</i> and a causative relation has been suggested. However, although NO can promote apoptosis, its actions vary with cell type. <h3>AIMS</h3> To determine whether exogenous NO, derived from an NO donor, might promote or counteract apoptosis in gastric mucous epithelial cells. <h3>METHODS</h3> Primary cultures of guinea pig gastric mucosal cells were exposed to the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) for 24 hours. Apoptosis was detected from nuclear staining with Hoechst 33258, in situ nick end labelling of DNA, and the presence of DNA “ladders” in cell extracts. Cyclic GMP content and caspase activity were determined by immunoassay and fluorimetric assay respectively. <h3>RESULTS</h3> SNAP 1 mM did not alter the small proportion of cells on the culture plate (3–6%) which exhibited features of apoptosis. However, SNAP produced an inhibition of apoptosis, and of caspase 3 like activity, when enhanced by 25 μM N-hexanoyl-d-sphingosine (C<sub>6</sub>-ceramide), or by detachment of cells from the culture plate. The guanylate cyclase inhibitor, 1H-1, 2, 4-oxadiazole-4, 3-a-quinoxaline-1-one (ODQ), prevented the stimulation of cyclic GMP by SNAP, but not the anti- apoptotic effects of the NO donor. The cyclic GMP analogues 8-bromo-cyclic GMP and 8-(4-chlorophenylthio) guanosine-3′,5′- cyclic monophosphate did not significantly inhibit apoptosis in the mucosal cells. <h3>CONCLUSIONS</h3> Exogenous NO inhibited apoptosis in guinea pig gastric mucous cells by a mechanism which did not involve elevation of cyclic GMP. NO, if produced from NO synthase during infection with<i> H pylori</i>, may therefore counter the proapoptotic effects of this pathogen.
Innate immunity to carcinomas?
Authors: S J C GOLBY
Journal: Gut (2000)

Human MHC class I-related molecules, MICA and MICB, are stress-induced antigens that are recognized by a subset of gamma delta T cells expressing the variable region Vdelta1.This functional association has been found to be limited to intestinal epithelium, where these T cells are prevalent and where MICA and, presumably, MICB are mainly expressed.However, increased frequencies of Vdelta1 gamma delta T cells have been observed in various epithelial tumors; moreover, MICA/B are expressed on diverse cultured epithelial tumor cells.With freshly isolated tumor specimens, expression of MICA/B was documented in many, but not all, carcinomas of the lung, breast, kidney, ovary, prostate, and colon.In tumors that were positive for MICA/B, the frequencies of Vdelta1 gamma delta T cells were significantly higher than in those that were negative.Vdelta1 gamma delta T cell lines and clones derived from diVerent tumors recognized MICA/B on autologous and heterologous tumor cells.In accord with previous evidence, no constraints were observed in these interactions, such as those imposed by specific peptide ligands.Thus, MICA/B are tumor-associated antigens that can be recognized, in an apparently unconditional manner, by a subset of tumorinfiltrating gamma delta T cells.These results raise the possibility that an induced expression of MICA/B, by conditions that may be related to tumor homeostasis and growth, could play a role in immune responses against tumors.
Wrist-Cutting Syndrome: The Meaning of a Gesture
Authors: RICHARD J. ROSENTHAL, CARL RINZLER, RITA WALLSH, EDMUND KLAUSNER
Journal: American Journal of Psychiatry (1972)

The phenomenon of repeated wrist cutting in young women, performed in a nonsuicidal manner, was studied through the use of a control group. Histories revealed a significant incidence of early physical illness and surgery and markedly abnormal patterns of menstruation. The subjects interviewed immediately after cutting described an inability to deal with specific feelings, leading to a state of depersonalization. They cut themselves in an effort to reintegrate, and seemed to know exactly what was necessary to accomplish this: seeing a certain amount of blood, feeling a degree of pain, or being able to look inside the gaping wound. The authors relate the wrist-cutting gestures to genital conflict, reactions to helplessness, and an inability to handle aggression.
Connexin 43 Downregulation and Dephosphorylation in Nonischemic Heart Failure Is Associated With Enhanced Colocalized Protein Phosphatase Type 2A
Authors: Xun Ai, Steven M. Pogwizd
Journal: Circulation Research (2004)

In nonischemic heart failure (HF), ventricular tachycardia initiates by a nonreentrant mechanism, but there is altered conduction (that could lead to re-entry) that could arise from changes in gap junctional proteins, especially connexin43 (Cx43). We studied Cx43 expression and phosphorylation state in the left ventricle (LV) from an arrhythmogenic rabbit model of nonischemic HF and from patients with HF attributable to idiopathic dilated cardiomyopathy. We also investigated the role of protein phosphatases that dephosphorylate Cx43—PP1 and PP2A. In HF rabbit LV, Cx43 mRNA and total protein were decreased by 29% and 34%, respectively ( P &lt;0.05 and P &lt;0.001). In controls, Cx43 was primarily in the phosphorylated state, but with HF there was a 64% increase in nonphosphorylated Cx43 (Cx43-NP, normalized to total Cx43; P &lt;0.05). Similar results were noted in HF rabbit myocytes ( P &lt;0.05) and in human idiopathic dilated cardiomyopathy LV ( P &lt;0.05). We found that PP1 and PP2A colocalized with Cx43 in rabbit LV. With HF, the level of colocalized PP2A increased &gt;2.5-fold ( P &lt;0.002), whereas colocalized PP1 was unchanged. We also found intercellular coupling (assessed by Lucifer Yellow dye transfer) was markedly reduced in HF. However, okadaic acid (10 nmol/L) reduced the amount of Cx43-NP and significantly improved cell coupling in HF. Thus, in nonischemic HF in rabbits and humans, there is a decrease in both Cx43 expression and phosphorylation that contributes to uncoupling. Increased levels of PP2A that colocalize with Cx43 can underlie enhanced levels of Cx43-NP in HF. Modulation of Cx43 phosphorylation may be a potential therapeutic target to improve conduction in HF.
Inhibition of LSD1 reduces herpesvirus infection, shedding, and recurrence by promoting epigenetic suppression of viral genomes
Authors: James M. Hill, Debra C. Quenelle, Rhonda D. Cardin, Jodi L. Vogel, Christian Clement, Fernando J. Bravo, Timothy P. Foster, Marta Bosch-Marce, Priya Raja, Jennifer S. Lee, David I. Bernstein, Philip R. Krause, David M. Knipe, Thomas M. Kristie
Journal: Science Translational Medicine (2014)

Epigenetic suppression of herpes simplex virus demonstrates an approach to control persistent viruses.
Clinical Inertia in Response to Inadequate Glycemic Control
Authors: Baiju R. Shah, Janet E. Hux, Andreas Laupacis, Bernard Zinman, Carl van Walraven
Journal: Diabetes Care (2005)

OBJECTIVE—Diabetic patients with inadequate glycemic control ought to have their management intensified. Failure to do so can be termed “clinical inertia.” Because data suggest that specialist care results in better control than primary care, we evaluated whether specialists demonstrated less clinical inertia than primary care physicians. RESEARCH DESIGN AND METHODS—Using administrative data, we studied all non-insulin-requiring diabetic patients in eastern Ontario aged 65 or older who had A1c results &amp;gt;8% between September 1999 and August 2000. Drug intensification was measured by comparing glucose-lowering drug regimens in 4-month blocks before and after the elevated A1c test and was defined as 1) the addition of a new oral drug, 2) a dose increase of an existing oral drug, or 3) the initiation of insulin. Propensity score-based matching was used to control for confounding between groups. RESULTS—There were 591 patients with specialist care and 1,911 with exclusively primary care. In the matched cohorts, 45.1% of patients with specialist care versus 37.4% with primary care had drug intensification (P = 0.009). Most of this difference was attributed to specialists’ more frequent initiation of insulin in response to elevated A1c. CONCLUSIONS—Fewer than one-half of patients with high A1c levels had intensification of their medications, regardless of specialty of their physician. Specialists were more aggressive with insulin initiation than primary care physicians, which may contribute to the lower A1c levels seen with specialist care. Interventions assisting patients and physicians to recognize and overcome clinical inertia should improve diabetes care in the population.
COPD: GOLD 2011 and implications for clinical practice
Authors: Dulce Apolinário, Ricardo Reis, Ana Isabel Loureiro, Cláudia Pinto, Abel Afonso
Journal: European Respiratory Journal (2013)

INTRODUCTION The 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) contains significant changes in terms of classification and treatment. AIMS To compare the GOLD 2011 and 2010 classification system in COPD patients and evaluation of its clinical and therapeutic implications. METHODS Application of both GOLD classifications in COPD patients followed in a Pulmonology consultation who consecutively performed pulmonary function tests (PFTs) from March to August/2012. Data were collected by clinical consultation or telephone interview, two weeks or less after PFTs. RESULTS Sixty-five patients were evaluated (69.2% men, mean age 68.8+10.7years), 58.5% with smoking habits. Using the GOLD 2010, 49.2% were stage II, 23.1% stage III, 13.8% stage IV and 13.8% stage I. With GOLD 2011, 40% belonged to group B, 38.5% group D, 15.4% group A and 6.2% group C. The mean COPD Assessment Test (CAT) score was 17.8+10.1. One year history of exacerbations was present in 49.2% patients. CAT score was correlated with FEV1 (r =-0.39) (p
Clinical subsequent fractures cluster in time after first fractures
Authors: T A C M van Geel, S van Helden, P P Geusens, B Winkens, G-J Dinant
Journal: Annals of the Rheumatic Diseases (2008)

Objectives: The risk of subsequent fractures is double the risk of having a first fracture. We analysed whether this risk is constant or not over time. Methods: A population-based study in 4140 postmenopausal women, aged between 50 and 90 years, on radiographic confirmed clinical fractures from menopause onwards analysed by Cox regression. Results: A total of 924 (22%) women had a first fracture and 243 (26% of 924) a subsequent fracture. Of all first fractures, 4% occurred in each year from menopause onwards, while after a first fracture 23% of all subsequent fractures occurred within 1 year and 54% within 5 years. When calculated from time of first fracture, the relative risk (RR) of subsequent fracture was 2.1 (95% CI 1.7 to 2.6) and remained increased over 15 years. When calculated for specific time intervals after a first fracture, the RR was 5.3 (95% CI 4.0 to 6.6) within 1 year, 2.8 (95% CI 2.0 to 3.6) within 2–5 years, 1.4 (95% CI 1.0 to 1.8) within 6–10 years and 0.41 (95% CI 0.29 to 0.53) after &gt;10 years. Conclusions: From menopause onwards, clinical fractures cluster in time, indicating the need for early action to prevent subsequent fractures.
Sirolimus-Eluting Stent Versus Paclitaxel-Eluting Stent for Patients With Long Coronary Artery Disease
Authors: Young-Hak Kim, Seong-Wook Park, Seung-Whan Lee, Duk-Woo Park, Sung-Cheol Yun, Cheol Whan Lee, Myeong-Ki Hong, Hyun-Sook Kim, Jae-Ki Ko, Jae-Hyeong Park, Jae-Hwan Lee, Si Wan Choi, In-Whan Seong, Yoon Haeng Cho, Nae-Hee Lee, June Hong Kim, Kook-Jin Chun, Seung-Jung Park
Journal: Circulation (2006)

Outcomes remain relatively unfavorable for stent-based coronary intervention of lesions with long diseased segments. This study compared sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) for long coronary lesions.The present randomized, multicenter, prospective study compared the use of long (> or =32 mm) SES with PES in 500 patients with long (> or =25 mm) native coronary lesions. The primary end point of the trial was the rate of binary in-segment restenosis according to follow-up angiography at 6 months. The SES and PES groups had similar baseline characteristics. Lesion length was 33.9+/-11.6 mm in the SES group and 34.5+/-12.6 mm in the PES group (P=0.527). The in-segment binary restenosis rate was significantly lower in the SES group than in the PES group (3.3% versus 14.6%; relative risk 0.23; P<0.001). In-stent late loss of lumen diameter was 0.09+/-0.37 mm in the SES group and 0.45+/-0.55 mm in the PES group (P<0.001). In patients with restenoses, a pattern of focal restenosis was more common in the SES group than in the PES group (100% versus 53.3%, P=0.031). Consequently, SES patients had a lower rate of target-lesion revascularization at 9 months (2.4% versus 7.2%, P=0.012). The incidence of death (0.8% in SES versus 0% in PES, P=0.499) or myocardial infarction (8.8% in SES versus 10.8% in PES, P=0.452) at 9 months of follow-up was not statistically different between the 2 groups.For patients with long native coronary artery disease, SES implantation was associated with a reduced incidence of angiographic restenosis and a reduced need for target-lesion revascularization compared with PES implantation.
Benefits and Adverse Events in Younger Versus Older Patients Receiving Neoadjuvant Chemotherapy for Osteosarcoma: Findings From a Meta-Analysis
Authors: Marnie Collins, Miriam Wilhelm, Rachel Conyers, Alan Herschtal, Jeremy Whelan, Stefan Bielack, Leo Kager, Thomas Kühne, Matthew Sydes, Hans Gelderblom, Stefano Ferrari, Piero Picci, Sigbjørn Smeland, Mikael Eriksson, Antonio Sérgio Petrilli, Archie Bleyer, David M. Thomas
Journal: Journal of Clinical Oncology (2013)

Purpose The LIVESTRONG Young Adult Alliance has conducted a meta-analysis of individual patient data from prospective neoadjuvant chemotherapy osteosarcoma studies and registries to examine the relationships of sex, age, and toxicity on survival. Patients and Methods Suitable data sets were identified by a survey of published data reported in PubMed. The final pooled data set comprised 4,838 patients from five international cooperative groups. Results After accounting for important variables known at study entry such as tumor location and histology, females experienced higher overall survival rates than males (P = .005) and children fared better than adolescents and adults (P = .002). Multivariate landmark analysis following surgery indicated that a higher rate of chemotherapy-induced tumor necrosis was associated with longer survival (P &lt; .001), as was female sex (P = .004) and the incidence of grade 3 or 4 mucositis (P = .03). Age group was not statistically significant in this landmark analysis (P = .12). Females reported higher rates of grade 3 or 4 thrombocytopenia relative to males (P &lt; .001). Children reported the highest rates of grade 3 or 4 neutropenia (P &lt; .001) and thrombocytopenia (P &lt; .001). The achievement of good tumor necrosis was higher for females than for males (P = .002) and for children than for adults (P &lt; .001). Conclusion These results suggest fundamental differences in the way chemotherapy is handled by females compared with males and by children compared with older populations. These differences may influence survival in a disease in which chemotherapy is critical to overall outcomes.
Drug synergies and the potential for combination therapy in onychomycosis
Authors: E.G.V. Evans
Journal: British Journal of Dermatology (2003)

Synergy between antifungal drugs is well recognized. However, combinations of antifungals are yet to be widely adopted to treat onychomycosis. The rationale for the combination of topical and oral therapy in the treatment of onychomycosis is that the systemic antifungal reaches the infection area via the nail bed and the topical agent is absorbed through the nail surface. The combination of antifungals used should ideally be synergistic in their mode of action. Synergy between amorolfine and other antifungals has been demonstrated in vitro. This is presumably due to differences in the precise point of action of the drugs on the fungal cell membrane, where they inhibit the synthesis of ergosterol. Thus, combinations can result in increased antifungal activity at lower concentrations of both drugs. The potential exists therefore for combinations of antifungals to achieve higher cure rates in onychomycosis, in a shorter time than is currently possible. This approach warrants further investigation.
Mental Health Problems, Use of Mental Health Services, and Attrition From Military Service After Returning From Deployment to Iraq or Afghanistan
Authors: Charles W. Hoge, Jennifer L. Auchterlonie, Charles S. Milliken
Journal: JAMA (2006)

ContextThe US military has conducted population-level screening for mental health problems among all service members returning from deployment to Afghanistan, Iraq, and other locations. To date, no systematic analysis of this program has been conducted, and studies have not assessed the impact of these deployments on mental health care utilization after deployment.ObjectivesTo determine the relationship between combat deployment and mental health care use during the first year after return and to assess the lessons learned from the postdeployment mental health screening effort, particularly the correlation between the screening results, actual use of mental health services, and attrition from military service.Design, Setting, and ParticipantsPopulation-based descriptive study of all Army soldiers and Marines who completed the routine postdeployment health assessment between May 1, 2003, and April 30, 2004, on return from deployment to Operation Enduring Freedom in Afghanistan (n = 16 318), Operation Iraqi Freedom (n = 222 620), and other locations (n = 64 967). Health care utilization and occupational outcomes were measured for 1 year after deployment or until leaving the service if this occurred sooner.Main Outcome MeasuresScreening positive for posttraumatic stress disorder, major depression, or other mental health problems; referral for a mental health reason; use of mental health care services after returning from deployment; and attrition from military service.ResultsThe prevalence of reporting a mental health problem was 19.1% among service members returning from Iraq compared with 11.3% after returning from Afghanistan and 8.5% after returning from other locations (P&lt;.001). Mental health problems reported on the postdeployment assessment were significantly associated with combat experiences, mental health care referral and utilization, and attrition from military service. Thirty-five percent of Iraq war veterans accessed mental health services in the year after returning home; 12% per year were diagnosed with a mental health problem. More than 50% of those referred for a mental health reason were documented to receive follow-up care although less than 10% of all service members who received mental health treatment were referred through the screening program.ConclusionsCombat duty in Iraq was associated with high utilization of mental health services and attrition from military service after deployment. The deployment mental health screening program provided another indicator of the mental health impact of deployment on a population level but had limited utility in predicting the level of mental health services that were needed after deployment. The high rate of using mental health services among Operation Iraqi Freedom veterans after deployment highlights challenges in ensuring that there are adequate resources to meet the mental health needs of returning veterans.
Randomized phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902
Authors: S Sugawara, S Oizumi, K Minato, T Harada, A Inoue, Y Fujita, M Maemondo, H Yoshizawa, K Ito, A Gemma, M Nishitsuji, M Harada, H Isobe, I Kinoshita, S Morita, K Kobayashi, K Hagiwara, M Kurihara, T Nukiwa
Journal: Annals of Oncology (2015)