tbuckley/cabot-search huggingface dataset:
The Effect of Ruboxistaurin on Nephropathy in Type 2 Diabetes
Authors: Katherine R. Tuttle, George L. Bakris, Robert D. Toto, Janet B. McGill, Kuolung Hu, Pamela W. Anderson
Journal: Diabetes Care (2005)

OBJECTIVE—Ruboxistaurin selectively inhibits protein kinase C-β and ameliorates kidney disease in animal models of diabetes. The purpose of this study was to evaluate the effects of ruboxistaurin on diabetic nephropathy in humans. RESEARCH DESIGN AND METHODS—A randomized, double-blind, placebo-controlled, multicenter, pilot study was performed to evaluate the effects of 32 mg/day ruboxistaurin for 1 year in persons (n = 123) with type 2 diabetes and persistent albuminuria (albumin-to-creatinine ratio [ACR] 200-2,000 mg/g), despite therapy with renin-angiotensin system inhibitors. The primary end point was a change in the ACR. Estimated glomerular filtration rate (eGFR) (four-component equation from the Modification of Diet in Renal Disease study) was also calculated. RESULTS—At baseline, urinary ACR was 764 ± 427 mg/g (means ± SD), and eGFR was 70 ± 24 ml/min per 1.73 m2. Systolic and diastolic blood pressures were 135 ± 14 and 75 ± 9 mmHg, respectively. HbA1c was 8.0 ± 1.2%. After 1 year, urinary ACR decreased significantly (−24 ± 9%) in participants treated with ruboxistaurin (P = 0.020) and nonsignificantly (−9 ± 11%) in the placebo group (P = 0.430). The ACR-lowering effect of ruboxistaurin appeared by 1 month. eGFR did not decline significantly in the ruboxistaurin group (−2.5 ± 1.9 ml/min per 1.73 m2) (P = 0.185), whereas the placebo group lost significant eGFR over 1 year (−4.8 ± 1.8 ml/min per 1.73 m2) (P = 0.009). Between-group differences for changes in ACR and eGFR were not statistically significant, but this pilot study was underpowered to determine such differences. CONCLUSIONS—In persons with type 2 diabetes and nephropathy, treatment with ruboxistaurin reduced albuminuria and maintained eGFR over 1 year. Ruboxistaurin may add benefit to established therapies for diabetic nephropathy.
Freeing phylogenies from artifacts of alignment.
Authors: J L Thorne, H Kishino
Journal: Molecular Biology and Evolution (1992)

Widely used methods for phylogenetic inference, both those that require and those that produce alignments, share certain weaknesses. These weaknesses are discussed, and a method that lacks them is introduced. For each pair of sequences in the data set, the method utilizes both insertion-deletion and amino acid replacement information to estimate a pairwise evolutionary distance. It is also possible to allow regional heterogeneity of replacement rates. Because a likelihood framework is adopted, the standard deviation of each pairwise distance can be estimated. The distance matrix and standard error estimates are used to infer a phylogenetic tree. As an example, this method is used on 10 widely diverged sequences of the second largest RNA polymerase subunit. A pseudo-bootstrap technique is devised to assess the validity of the inferred phylogenetic tree.
Contribution of Kv Channels to Phenotypic Remodeling of Human Uterine Artery Smooth Muscle Cells
Authors: Eduardo Miguel-Velado, Alejandro Moreno-Domínguez, Olaia Colinas, Pilar Cidad, Magda Heras, M. Teresa Pérez-García, José Ramón López-López
Journal: Circulation Research (2005)

Vascular smooth muscle cells (VSMCs) perform diverse functions that can be classified into contractile and synthetic (or proliferating). All of these functions can be fulfilled by the same cell because of its capacity of phenotypic modulation in response to environmental changes. The resting membrane potential is a key determinant for both contractile and proliferating functions. Here, we have explored the expression of voltage-dependent K+ (Kv) channels in contractile (freshly dissociated) and proliferating (cultured) VSMCs obtained from human uterine arteries to establish their contribution to the functional properties of the cells and their possible participation in the phenotypic switch. We have studied the expression pattern (both at the mRNA and at the protein level) of Kvalpha subunits in both preparations as well as their functional contribution to the K+ currents of VSMCs. Our results indicate that phenotypic remodeling associates with a change in the expression and distribution of Kv channels. Whereas Kv currents in contractile VSMCs are mainly performed by Kv1 channels, Kv3.4 is the principal contributor to K+ currents in cultured VSMCs. Furthermore, selective blockade of Kv3.4 channels resulted in a reduced proliferation rate, suggesting a link between Kv channels expression and phenotypic remodeling.
Clostridium perfringens Wound Infection Associated With Elastic Bandages
Authors: Richard D. Pearson
Journal: JAMA (1980)

Clostridium perfringens wound infections were associated with the use of nonsterile elastic outer bandages in diabetic patients who had undergone lower extremity amputation for vascular insufficiency. In each case a second surgical procedure was required. Elastic bandages similar to those used in these procedures were found to contain C perfringens and other clostridial species. This report illustrates the need for maintenance of a sterile, nonpermeable inner barrier to prevent transudation of bacteria into the wound and the potential benefit of using sterile elastic outer bandages after amputation for vascular insufficiency.
Surgery for primary supratentorial brain tumors in the United States, 1988 to 2000: The effect of provider caseload and centralization of care
Authors: Fred G. Barker, William T. Curry, Bob S. Carter
Journal: Neuro-Oncology (2005)

Contemporary reports of patient outcomes after biopsy or resection of primary brain tumors typically reflect results at specialized centers. Such reports may not be representative of practices in nonspecialized settings. This analysis uses a nationwide hospital discharge database to examine trends in mortality and outcome at hospital discharge in 38,028 admissions for biopsy or resection of supratentorial primary brain tumors in adults between 1988 and 2000, particularly in relation to provider caseload. Multivariate analyses showed that large-volume centers had lower in-hospital postoperative mortality rates than centers with lighter caseloads, both for craniotomies (odds ratio [OR] 0.75 for a tenfold larger caseload) and for needle (closed) biopsies (OR 0.54). Adverse discharge disposition was also less likely at high-volume hospitals, both for craniotomies (OR 0.77) and for needle biopsies (OR 0.67). The annual number of surgical admissions increased by 53% during the 12-year study period, and in-hospital mortality rates decreased during this period, from 4.8% to 1.8%. Mortality rates decreased over time, both for craniotomies and for needle biopsies. Subgroup analyses showed larger relative mortality rate reductions at large-volume centers than at small-volume centers (73% vs. 43%, respectively). The number of US hospitals performing one or more craniotomies annually for primary brain tumors decreased slightly, and the number performing needle biopsies increased. There was little change in median hospital annual craniotomy caseloads, but the largest centers had disproportionate growth in volume. The 100 highest-caseload US hospitals accounted for an estimated 30% of the total US surgical primary brain tumor caseload in 1988 and 41% in 2000. Our findings do not establish minimum volume thresholds for acceptable surgical care of primary brain tumors. However, they do suggest a trend toward progressive centralization of craniotomies for primary brain tumor toward large-volume US centers during this interval.
The Preventive Polypill — Much Promise, Insufficient Evidence
Authors: K. Srinath Reddy
Journal: New England Journal of Medicine (2007)

Interview with K. Srinath Reddy on the burden of chronic disease in India and the developing world. (06:50)Download The rapidly increasing global burdens of cardiovascular disease and diabetes call for interventions that have a population-wide effect, as well as interventions that identify and protect individual patients who have a high risk of major adverse events. Such actions are especially needed in low-income and middle-income countries, which can ill afford the huge losses in human and financial resources that will result from unchecked development of clinical disease.1Many drugs have been found to be highly effective in the primary or secondary prevention of cardiovascular disease. These include aspirin, angiotensin-converting–enzyme (ACE) inhibitors, statins, beta-blockers, and calcium-channel blockers. Despite their potential . . .
39 ANTI-EGFR MONOCLONAL ANTIBODY INHIBITS HEPATITIS C VIRUS INFECTION BY MODULATION OF EGFR SIGNALING
Authors: L. Zona, J. Lupberger, I. Fofana, C. Thumann, M.N. Zahid, F. Xiao, M. Turek, C.J. Mee, H. Harris, J.A. Mc Keating, M. Doffoë, M.B. Zeisel, T.F. Baumert
Journal: Journal of Hepatology (2011)
Gemtuzumab ozogamicin (MylotargTM) is infrequently associated with sinusoidal obstructive syndrome/veno-occlusive disease
Authors: C. Nabhan, L. Rundhaugen, M. Jatoi, M.B. Riley, L. Boehlke, L.C. Peterson, M.S. Tallman
Journal: Annals of Oncology (2004)
Bad teeth and myocardial infarction. Smokers neglect their teeth.
Authors: R J van Es
Journal: BMJ (1993)

Thyroid eye diseaseMore treatment options EDrTOR,-Donald Munro clearly reviews the pathogenesis and treatment of dysthyroid eye disease.'There are, however, alternative treat- ments which merit consideration.Lid retraction may be asymptomatic but a considerable proportion of patients benefit from upper or lower eyelid lengthening procedures.2These can be very effective in improving the cosmetic appearance and protecting the cornea.These procedures are preferable to lateral tarsor- rhaphy because the cosmetic results are better and anterior displacement of the globe is not restricted (thus lessening the risk of optic nerve compression).High dose steroid treatment is effective in relieving compressive optic neuropathy, but the disease often progresses when the dose is gradually reduced to a more modest level.So, in many cases, long term maintenance treatment is required.Local treatment is therefore preferable and avoids the well known side effects of steroids.Surgical decompression of the orbit into the maxillary and ethmoid sinuses is a successful procedure for many patients, including those for whom the "eye signs are disfiguring or disabling."Complications include double vision due to stra- bismus and infraorbital hypoaesthesia.Radiotherapy is dismissed by Munro: "Britain has few enthusiasts for local irradiation of the orbit."Carefully planned low dose external beam radiotherapy is very effective in patients with progressive disease,34 particularly disease of less than two years' duration.The long term risk of neoplasia is low.It is negligible in elderly patients, for whom this treatment is particularly indicated because of the problems associated with taking steroids long term.
Class III β-Tubulin in Advanced NSCLC of Adenocarcinoma Subtype Predicts Superior Outcome in a Randomized Trial
Authors: Adam Christian Vilmar, Eric Santoni-Rugiu, Jens Benn Sørensen
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Platinum-based doublets are the cornerstone of treatment in advanced non–small-cell lung cancer (NSCLC) and often include vinorelbine or taxanes. A predictive biomarker is greatly needed to select chemotherapy-sensitive patients for these microtubule-interfering agents. Class III β-tubulin (TUBB3) has been shown of value in NSCLC, but evidence is not uniform. Accordingly, we explored the predictive role of TUBB3 in advanced NSCLC. Experimental Design: Four hundred forty-three patients with advanced NSCLC were enrolled in a phase III trial and randomized to vinorelbine- or paclitaxel-containing chemotherapy. Immunohistochemical evaluation of TUBB3 status was mainly done on bioptic material and correlated to response rates, progression-free survival (PFS), overall survival (OS), quality of life (QOL), and toxicity. Results: Two hundred sixty-one (58.9%) patients had representative tissue samples for TUBB3 evaluation. Patients with TUBB3-negative adenocarcinomas had a significantly prolonged PFS and OS when compared with the opposite subgroup (7.87 vs. 6.83 months, P = 0.035 and 14.17 vs. 11.17 months, P = 0.018, respectively). Multivariate analyses revealed an HR of 1.55 (95% CI, 1.04–2.31, P = 0.032) for TUBB3-positive adenocarcinoma patients. TUBB3-negative adenocarcinoma patients showed a mean QOL decline of −18.25 points (95% CI, −4.28 to −32.22, P = 0.013) as compared with −3.86 (95% CI, −7.0 to 15.52, P = 0.5). Conclusion: TUBB3 was of predictive value in adenocarcinoma patients in the largest, randomized advanced NSCLC population published to date. It may be clinically useful in conjunction with other biomarkers, but QOL information should be recorded during validation, as prophylactic intervention may be needed in specific subgroups at risk of toxicity. Clin Cancer Res; 17(15); 5205–14. ©2011 AACR.
Activation and Functional Significance of the Renin-Angiotensin System in Mice With Cardiac Restricted Overexpression of Tumor Necrosis Factor
Authors: Markus Flesch, Anje Höper, Louis Dell’Italia, Kenda Evans, Richard Bond, Ronald Peshock, Abhinav Diwan, Theresa A. Brinsa, Chih-Chang Wei, Natarajan Sivasubramanian, Francis G. Spinale, Douglas L. Mann
Journal: Circulation (2003)

The functional significance of cross-regulation between the renin-angiotensin system (RAS) and tumor necrosis factor (TNF) has been established in nonmyocyte cell types; however, the degree and functional significance of the interaction between RAS and TNF has not been characterized in the heart.We examined the expression of components of the RAS in a line of transgenic mice (MHCsTNF) with cardiac restricted overexpression of TNF. When examined at 4, 8, and 12 weeks of age, the MHCsTNF mice had increased activation of myocardial RAS, as shown by an increase in ACE mRNA level and ACE activity and increased angiotensin II peptide levels. Furthermore, myocardial angiotensin receptor mRNA and protein levels were reduced in the MHCsTNF mice, consistent with homologous desensitization of the receptors. However, expression of renin and angiotensinogen was not increased in MHCsTNF mice compared with littermate controls. To determine the functional significance of RAS activation in the MHCsTNF mice, we treated the mice with an angiotensin type I receptor antagonist, losartan (30 mg/kg), or diluent from 4 to 8 weeks of age. Analysis of cardiac structure with MRI showed that treatment with losartan normalized left ventricular mass and wall thickness. Furthermore, treatment with losartan reduced myocardial collagen content and reduced the incidence of myocyte apoptosis.Taken together, these results show that there are functionally significant interactions between RAS and TNF in the heart and that these interactions play an important role in the development and progression of left ventricular remodeling.
Capecitabine and Trastuzumab in Heavily Pretreated Metastatic Breast Cancer
Authors: Rupert Bartsch, Catharina Wenzel, Gabriela Altorjai, Ursula Pluschnig, Margaretha Rudas, Robert M. Mader, Michael Gnant, Christoph C. Zielinski, Guenther G. Steger
Journal: Journal of Clinical Oncology (2007)

Purpose In human epidermal growth factor 2 (HER-2)–positive advanced breast cancer, taxanes or vinorelbine plus trastuzumab are among the most widely applied options in the first-line setting. We evaluated the efficacy and tolerability of capecitabine plus trastuzumab after anthracycline and docetaxel or vinorelbine failure and prior trastuzumab exposure. Patients and Methods Forty consecutive patients were included. Capecitabine was administered at a dose of 1,250 mg/m 2 bid for 14 consecutive days in 3-week cycles, with dose modifications if necessary. Trastuzumab was administered every 3 weeks. Time to progression (TTP) was defined as primary end point. Response was evaluated every 3 months using International Union Against Cancer criteria. Results TTP was a median of 8 months, and overall survival was 24 months. No significant difference was found for second-line and beyond second-line treatment. A complete response (CR) was observed in 2.5%, partial response (PR) in 17.5%, stable disease lasting at least 6 months (SD) in 50%, resulting in a clinical benefit rate (CR + PR + SD ≥ 6 months) of 70%. Diarrhea (5%) and hand-foot syndrome (15%) were the only treatment-related adverse events that occurred with grade 3 or 4 intensity. Three patients (7.5%) developed brain metastases while receiving therapy. Conclusion Capecitabine plus trastuzumab appears to be an effective and safe option in a heavily pretreated population. Therefore, a direct comparison of this regimen with capecitabine monotherapy in this setting is warranted.
HIN-1, an Inhibitor of Cell Growth, Invasion, and AKT Activation
Authors: Ian Krop, Michele Taylor Parker, Noga Bloushtain-Qimron, Dale Porter, Rebecca Gelman, Hidefumi Sasaki, Matthew Maurer, Mary Beth Terry, Ramon Parsons, Kornelia Polyak
Journal: Cancer Research (2005)

Abstract The HIN-1 gene encoding a small, secreted protein is silenced due to methylation in a substantial fraction of breast, prostate, lung, and pancreatic carcinomas, suggesting a potential tumor suppressor function. The receptor of HIN-1 is unknown, but ligand-binding studies indicate the presence of high-affinity cell surface HIN-1 binding on epithelial cells. Here, we report that HIN-1 is a potent inhibitor of anchorage-dependent and anchorage-independent cell growth, cell migration, and invasion. Expression of HIN-1 in synchronized cells inhibits cell cycle reentry and the phosphorylation of the retinoblastoma protein (Rb), whereas in exponentially growing cells, HIN-1 induces apoptosis without apparent cell cycle arrest and effect on Rb phosphorylation. Investigation of multiple signaling pathways revealed that mitogen-induced phosphorylation and activation of AKT are inhibited in HIN-1–expressing cells. In addition, expression of constitutively activate AKT abrogates HIN-1–mediated growth arrest. Taken together, these studies provide further evidence that HIN-1 possesses tumor suppressor functions, and that these activities may be mediated through the AKT signaling pathway.
Long-Term, Open-Label Study of Risperidone in Children With Severe Disruptive Behaviors and Below-Average IQ
Authors: Robert L Findling, Michael G Aman, Marielle Eerdekens, Albert Derivan, Ben Lyons
Journal: American Journal of Psychiatry (2004)

This study determined the long-term safety and effectiveness of risperidone in treating severe disruptive behavior in children with subaverage intelligence.This 48-week, open-label extension included 107 children ages 5-12 years with severe disruptive behavior disorders (according to DSM-IV criteria and a score of > or = 24 on the conduct problem subscale of the Nisonger Child Behavior Rating Form) and subaverage intelligence (IQ 36-84) who completed at least 2 weeks of a randomized, double-blind, placebo-controlled study of risperidone. All patients received 0.02-0.06 mg/kg/day of oral risperidone; the purpose was to accumulate long-term safety data. Scores on the Nisonger Child Behavior Rating Form were also obtained.The mean risperidone dose was 1.5 mg/day. The most common adverse events reported were somnolence (33%), headache (33%), rhinitis (28%), and weight gain (21%). Somnolence was usually mild and transient. The mean weight increase was 5.5 kg; half was attributable to developmentally expected growth. Transient and asymptomatic increases in prolactin levels were observed. There were no significant changes in Extrapyramidal Symptom Rating Scale scores and no cases of tardive dyskinesia. No clinically relevant changes in ECGs or vital signs were noted. Risperidone was associated with rapid, significant improvement on the conduct problem subscale score of the Nisonger Child Behavior Rating Form in patients previously treated with placebo; improvement was maintained during long-term treatment and in patients previously given risperidone.Long-term risperidone appears to be generally safe, well tolerated, and effective for treating severely disruptive behaviors in children with subaverage intelligence.
Transmembrane carbonic anhydrase, MN/CA IX, is a potential biomarker for biliary tumours
Authors: Juha Saarnio, Seppo Parkkila, Anna-Kaisa Parkkila, Silvia Pastoreková, Kari Haukipuro, Jaromir Pastorek, Tatu Juvonen, Tuomo J Karttunen
Journal: Journal of Hepatology (2001)
Peroxisome Proliferator-Activated Receptor γ Plays a Critical Role in Inhibition of Cardiac Hypertrophy In Vitro and In Vivo
Authors: Masayuki Asakawa, Hiroyuki Takano, Toshio Nagai, Hiroki Uozumi, Hiroshi Hasegawa, Naoto Kubota, Toshihiro Saito, Yoshiaki Masuda, Takashi Kadowaki, Issei Komuro
Journal: Circulation (2002)

Peroxisome proliferator-activated receptors (PPARs) are transcription factors of the nuclear receptor superfamily. It has been reported that the thiazolidinediones, which are antidiabetic agents and high-affinity ligands for PPARgamma, regulate growth of vascular cells. In the present study, we examined the role of PPARgamma in angiotensin II (Ang II)-induced hypertrophy of neonatal rat cardiac myocytes and in pressure overload-induced cardiac hypertrophy of mice.Treatment of cultured cardiac myocytes with PPARgamma ligands such as troglitazone, pioglitazone, and rosiglitazone inhibited Ang II-induced upregulation of skeletal alpha-actin and atrial natriuretic peptide genes and an increase in cell surface area. Treatment of mice with a PPARgamma ligand, pioglitazone, inhibited pressure overload-induced increases in the heart weight-to-body weight ratio, wall thickness, and myocyte diameter in wild-type mice and an increase in the heart weight-to-body weight ratio in heterozygous PPARgamma-deficient mice. In contrast, pressure overload-induced increases in the heart weight-to-body weight ratio and wall thickness were more prominent in heterozygous PPARgamma-deficient mice than in wild-type mice.These results suggest that the PPARgamma-dependent pathway is critically involved in the inhibition of cardiac hypertrophy.
Quantitative Study of Signal Hyperintensities on T<sub>2</sub>-Weighted Magnetic Resonance Imaging in Late-Onset Schizophrenia
Authors: P Sachdev, H Brodaty
Journal: American Journal of Psychiatry (1999)

The authors investigated the extent and distribution of signal hyperintensities on T2-weighted magnetic resonance imaging (MRI) of the brains of subjects with late-onset schizophrenia.The study group consisted of 25 subjects with DSM-III-R schizophrenia and onset at age 50 or more years (late-onset schizophrenia) matched group-wise with 24 subjects with early-onset schizophrenia and 30 psychiatrically healthy volunteers. The subjects underwent clinical and neuropsychological assessments and MRI scans. Transaxial T2-weighted and proton-density images were analyzed manually for signal hyperintensities in cerebral and cerebellar white matter, the basal ganglia, thalamus, and brainstem, and quantitative measures were obtained.Subjects with late-onset schizophrenia had greater periventricular hyperintensities measured as widths of periventricular rims and frontal and occipital caps than the two comparison groups. Hyperintense signals elsewhere in the white matter and in the basal ganglia and brainstem did not differ between groups, but the late-onset schizophrenia group had more signal hyperintensities in the thalamus than the normal comparison group. Signal hyperintensities in the frontal-subcortical circuit regions, when considered together, did not differ between groups. Periventricular hyperintensities had significant negative correlations with intelligence, memory, and frontal-executive functioning in the total group.The finding of increased periventricular hyperintensities and thalamic signal hyperintensities in late-onset schizophrenia suggests the possibility that cerebrovascular disease, in an interaction with some incompletely understood vulnerability factors, may play a role in the pathogenesis of schizophrenia with onset in advanced age.