tbuckley/cabot-search huggingface dataset:
Both Low and High 24-Hour Diastolic Blood Pressure Are Associated With Worse Cognitive Performance in Type 2 Diabetes: The Maastricht Study
Authors: Peggy J.J. Spauwen, Martin P.J. van Boxtel, Frans R.J. Verhey, Sebastian Köhler, Simone J.S. Sep, Annemarie Koster, Pieter C. Dagnelie, Ronald M.A. Henry, Nicolaas C. Schaper, Carla J.H. van der Kallen, Miranda T. Schram, Abraham A. Kroon, Coen D.A. Stehouwer
Journal: Diabetes Care (2015)

OBJECTIVE Hypertension and diabetes are both risk factors for cognitive decline, and individuals with both might have an especially high risk. We therefore examined linear and nonlinear (quadratic) associations of 24-h blood pressure (BP) with cognitive performance in participants with and without type 2 diabetes. We also tested the association of nocturnal dipping status with cognitive performance. RESEARCH DESIGN AND METHODS This study was performed as part of the Maastricht Study, an ongoing population-based cohort study. Cross-sectional associations of 24-h BP (n = 713, of whom 201 had type 2 diabetes) and nocturnal dipping status (n = 686, of whom 196 had type 2 diabetes) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition were tested using linear regression analysis and adjusted for demographics, vascular risk factors, cardiovascular disease, depression, and lipid-modifying and antihypertensive medication use. RESULTS After full adjustment, we found quadratic (inverted U-shaped) associations of 24-h diastolic blood pressure (DBP) with information processing speed (b for quadratic term = −0.0267, P &amp;lt; 0.01) and memory (immediate word recall: b = −0.0180, P &amp;lt; 0.05; delayed word recall: b = −0.0076, P &amp;lt; 0.01) in participants with diabetes, but not in those without. No clear pattern was found for dipping status. CONCLUSIONS This study shows that both low and high 24-h DBP are associated with poorer performance on tests of information processing speed and memory in individuals with type 2 diabetes.
The issue of bioavailability of oral low dose methotrexate: should we choose only 10 mg of MTX a week in conjunction with anti-TNF therapy?
Authors: Henning Zeidler
Journal: Annals of the Rheumatic Diseases (2014)

I read with interest the article by Burmester et al 1 on the efficacy and safety of ascending methotrexate (MTX) dose in combination with adalimumab. Increasing doses of oral at 2.5, 5, 10 or 20 mg weekly in combination with adalimumab demonstrated a statistically significant trend in improved clinical outcomes in early rheumatoid arthritis (RA) patients but efficacy of 10 and 20 mg/week MTX in combination with adalimumab therapy appeared equivalent. The authors suggest because of patient-reported treatment satisfaction, clinical efficacy and pharmacokinetics for patients initiating adalimumab combination therapy, the optimal starting dose may be lower than previously assumed; the treating physicians may consider 10 mg of MTX a week when deciding which dose of MTX to choose in conjunction with antitumour necrosis factor (anti-TNF) therapy and this presents an opportunity to lower MTX dosage in patients with RA.

Several reasons may militate against generalising this suggestion based on the …
Inhibiton of tumor-derived prostaglandin-e2 prevents the induction of human myeloid-derived suppressor cells (MDSCs) and rescues anti-tumor immunity
Authors: Yumeng Mao, Dhifaf Sarhan, Isabel Poschke, Andreas Lundqvist, Rolf Kiessling
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Cancer progression is associated with a severe impairment of anti-tumor immune responses. The accumulation of peripheral blood CD14+HLA-DRlo/- monocytic MDSCs has been identified as a prognostic factor in advanced stage melanoma patients. These cells suppress T cell functions ex
Immune Therapy in GI Malignancies: A Review
Authors: Judy Wang, Kim A. Reiss, Rina Khatri, Elizabeth Jaffee, Dan Laheru
Journal: Journal of Clinical Oncology (2015)

The balance between tumor-promoting and tumor-suppressing immune responses and the difference between them ultimately determine whether a cancer escapes immune recognition mechanisms. Defining the complex relationships between the tumor itself, the tumor environment, and the immune system has been critical in facilitating the development of successful immunotherapies. This review explores the role of oncogenes in inducing cancer-associated inflammation, the local and systemic factors that lead to immune suppression, and immunotherapy approaches to overcome immune privilege.
Rituximab in Idiopathic Membranous Nephropathy
Authors: Piero Ruggenenti, Carlos Chiurchiu, Varusca Brusegan, Mauro Abbate, Annalisa Perna, Claudia Filippi, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Currently available monoclonal antibodies against the B cell surface antigen CD20 have been employed to explore whether specific inhibition of B cells may help improve the outcome of idiopathic membranous nephropathy (IMN) and may avoid the side effects of steroids and immunosuppressants. This prospective, observational study evaluated the 1-yr outcome of eight IMN patients with persistent (>6 mo) urinary protein excretion > 3.5 g/24 h given four weekly infusions of the anti-CD20 antibody rituximab (375 mg/m2). At 3 and 12 mo, proteinuria significantly decreased from mean (± SD) 8.6 ± 4.2 to 4.3 ± 3.3 (−51%, P < 0.005) and 3.0 ± 2.5 (−66%, P < 0.005) g/24 h, albumin fractional clearance from 2.3 ± 2.1 to 1.2 ± 1.7 (−47%, P < 0.05) and 0.5 ± 0.6 (−76%, P < 0.003), and serum albumin concentration increased from 2.7 ± 0.5 to 3.1 ± 0.3 (+21%, P < 0.05) and 3.5 ± 0.4 (+41%, P < 0.05) mg/dl. At 12 mo, proteinuria decreased to ≤0.5 g/24 h or ≤3.5 g/24 h in two and three patients, respectively. Proteinuria decreased in the remaining patients by 74%, 44%, and 41%, respectively. Body weight, diastolic BP, and serum cholesterol progressively decreased in parallel with an improvement of edema in all patients. Renal function stabilized (Δ1/creatinine: +0.002 ± 0.007). CD20 B lymphocytes fell below normal ranges up to study-end. No patient had major drug-related events or major changes in other laboratory parameters. Rituximab thus promotes sustained disease remission in patients otherwise predicted to progress to ESRD, and it is safe. The long-term risk/benefit profile of this novel, disease-specific approach seems much more favorable to that of commonly employed immunosuppressive drugs. E-mail: [email protected]
Sustained Reduction of Aldosterone in Response to the Angiotensin Receptor Blocker Valsartan in Patients With Chronic Heart Failure
Authors: Jay N. Cohn, Inder S. Anand, Roberto Latini, Serge Masson, Yann-Tong Chiang, Robert Glazer
Journal: Circulation (2003)

Aldosterone has been implicated in the progression of heart failure. The Valsartan Heart Failure Trial (Val-HeFT) provided the first opportunity to examine the long-term effects of an angiotensin receptor blocker on plasma aldosterone levels in patients with NYHA class II through IV heart failure.Plasma aldosterone was measured by radioimmunoassay in core laboratories at baseline and during follow-up in patients assigned to valsartan at a target dose of 160 mg twice daily or placebo. In the placebo group, aldosterone (baseline, 150+/-160 pg/mL, mean+/-SD; n=2025) increased at 4, 12, and 24 months. In the valsartan group, aldosterone (baseline, 137+/-124 pg/mL, mean+/-SD; n=2023) decreased at 4 months and remained suppressed for up to 2 years. At end point (last measurement in each patient), mean aldosterone increased by 17.8+/-3.0 pg/mL (SEM) (11.9%) in the placebo group and decreased by 23.8+/-3.0 pg/mL (SEM) (-17.4%) in the valsartan group (P<0.00001). The effect of valsartan was similar in all subgroups, including those receiving neither ACE inhibitors (ACE-I) nor beta-blockers (BB) at baseline and those receiving concomitant ACE-I or BB. In contrast, outcome effects varied in the 4 subgroups, with a statistically significant reduction in the combined mortality/morbidity end point in those receiving neither neurohormonal inhibitor and an adverse trend in those treated with both drugs.Valsartan added to background therapy for heart failure produces sustained reduction in plasma aldosterone, consistent with the observed significant reduction in the combined mortality/morbidity end point. A similar reduction in all subgroups based on ACE-I or BB therapy, despite differing clinical outcomes in these subgroups, suggests that aldosterone plasma levels may not be a critical marker of the progression of heart failure.
Challenges and controversies in thoracic oncology: a new ERJ series
Authors: J.-P. Sculier, B. Besse, P. Van Schil
Journal: European Respiratory Journal (2014)

Appearing in the present issue of European Respiratory Journal is the first article of a new series dealing with challenges and controversies in thoracic oncology. The uniqueness of the series lies in the multidisciplinary approach to the choice of the topics and authors. Indeed, thoracic oncology, which mainly deals with the most important cancer in term of mortality, is involved in many medical disciplines: epidemiology, pathology, biology, chest medicine, imaging, medical oncology, radiation oncology, surgical oncology, and so on. Care proposals are today decided in multidisciplinary conferences where all those specialties should be represented and where the chest physician has a key role [1–3]. In addition, our knowledge about malignant diseases …
Pregnancy alters glucose-6-phosphate dehydrogenase trafficking, cell metabolism, and oxidant release of maternal neutrophils
Authors: Andrei L. Kindzelskii, Ji-Biao Huang, Tinnakorn Chaiworapongsa, Ryan M. Fahmy, Yeon Mee Kim, Roberto Romero, Howard R. Petty
Journal: Journal of Clinical Investigation (2002)

Pregnancy is associated with changes in host susceptibility to infections and inflammatory disease. We hypothesize that metabolic enzyme trafficking affects maternal neutrophil activation. Specifically, immunofluorescence microscopy has shown that glucose-6-phosphate dehydrogenase (G-6-PDase), the rate-controlling step of the hexose monophosphate shunt (HMS), is located near the cell periphery in control neutrophils but is found near the microtubule-organizing centers in cells from pregnant women. Cytochemical studies confirmed that the distribution of the G-6-PDase antigen is coincident with functional G-6-PDase activity. Metabolic oscillations within activated pregnancy neutrophils are higher in amplitude, though lower in frequency, than activated control neutrophils, suggesting limited HMS activity. Analysis of radioisotope-labeled carbon flux from glucose to CO(2) indicates that the HMS is intact in leukocytes from pregnant women, but its level is not enhanced by cell stimulation. Using extracellular fluorescent markers, activated pregnancy neutrophils were found to release reactive oxygen metabolites (ROMs) at a lower rate than activated control neutrophils. However, basal levels of ROM production in polarized pregnancy neutrophils were greater than in control neutrophils. Microtubule-disrupting agents reversed the observed changes in G-6-PDase trafficking, metabolic oscillations, and ROM production by maternal neutrophils. G-6-PDase trafficking appears to be one mechanism regulating ROM production by maternal neutrophils.
Confirmatory Factor Analysis of DSM-IV Criteria for Borderline Personality Disorder: Findings From the Collaborative Longitudinal Personality Disorders Study
Authors: Charles A. Sanislow, Carlos M. Grilo, Leslie C. Morey, Donna S. Bender, Andrew E. Skodol, John G. Gunderson, M. Tracie Shea, Robert L. Stout, Mary C. Zanarini, Thomas H. McGlashan
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study tested the factor structure of the DSM-IV criteria for borderline personality disorder by using confirmatory methods for the analysis of covariance structures in a large group from a multisite study. METHOD: A total of 668 primarily treatment-seeking subjects were reliably assessed for personality disorders by using the Diagnostic Interview for DSM-IV Personality Disorders. Associations among criteria for borderline personality disorder were examined. A confirmatory factor analysis was performed to test diagnosis as a unitary construct and to test an earlier-reported three-factor model comprising disturbed relatedness, behavioral dysregulation, and affective dysregulation. The three-factor model was subsequently tested by using a subset (N=498) of the study group that was reassessed 2 years later by independent evaluators who were blind to original diagnoses. RESULTS: Internal consistency of the borderline personality disorder diagnosis was adequate for both baseline and follow-up assessments. A confirmatory factor analysis model testing the borderline personality disorder diagnosis as a unitary construct provided good fit, and the three-factor model offered a significantly better fit for the baseline assessment. The three-factor model was replicated with the 2-year follow-up data. CONCLUSIONS: The diagnostic criteria for borderline personality disorder appear to reflect a statistically coherent construct. Three homogeneous components were supported empirically, lending conceptual clarity to different classes of the criteria for borderline personality disorder.
Prevention of Alcohol Withdrawal Seizures: The Roles of Diphenylhydantoin and Chlordiazepoxide
Authors: EMIL ROTHSTEIN
Journal: American Journal of Psychiatry (1973)

Two hundred patients with histories of chronic alcoholism and recent bouts of heavy and uncontrolled drinking were treated for alcohol withdrawal symptoms through the use of chlordiazepoxide and thiamine. One hundred of these patients, chosen at random, also received diphenylhydantoin. No withdrawal seizures occurred in either group, nor were any other differences observed. Patients with a history of previous withdrawal seizures were included in both treatment groups. These observations suggest that when adequate doses of chlordiazepoxide and thiamine are used during alcohol withdrawal, no additional anticonvulsant drug is needed to prevent seizures.
Effect of Ezetimibe on Hepatic Fat, Inflammatory Markers, and Apolipoprotein B-100 Kinetics in Insulin-Resistant Obese Subjects on a Weight Loss Diet
Authors: Dick C. Chan, Gerald F. Watts, Seng Khee Gan, Esther M.M. Ooi, P. Hugh R. Barrett
Journal: Diabetes Care (2010)

OBJECTIVE Nonalcoholic fatty liver disease is highly prevalent in obese and type 2 diabetic individuals and is strongly associated with dyslipidemia and inflammation. Weight loss and/or pharmacotherapy are commonly used to correct these abnormalities. RESEARCH DESIGN AND METHODS We performed a 16-week intervention trial of a hypocaloric, low-fat diet plus 10 mg/day ezetimibe (n = 15) versus a hypocaloric, low-fat diet alone (n = 10) on intrahepatic triglyceride (IHTG) content, plasma high sensitivity–C-reactive protein (hs-CRP), adipocytokines, and fetuin-A concentrations and apolipoprotein (apo)B-100 kinetics in obese subjects. ApoB-100 metabolism was assessed using stable isotope tracer kinetics and compartmental modeling; liver and abdominal fat contents were determined by magnetic resonance techniques. RESULTS Both weight loss and ezetimibe plus weight loss significantly (all P &amp;lt; 0.05) reduced body weight, visceral and subcutaneous adipose tissues, insulin resistance and plasma triglycerides, VLDL–apoB-100, apoC-III, fetuin-A, and retinol-binding protein-4 and increased plasma adiponectin concentrations. Compared with weight loss alone, ezetimibe plus weight loss significantly (all P &amp;lt; 0.05) decreased IHTG content (−18%), plasma hs-CRP (−53%), interleukin-6 (−24%), LDL cholesterol (−18%), campesterol (−59%), and apoB-100 (−14%) levels, with a significant increase in plasma lathosterol concentrations (+43%). The LDL–apoB-100 concentration also significantly fell with ezetimibe plus weight loss (−12%), chiefly owing to an increase in the corresponding fractional catabolic rate (+29%). The VLDL–apoB-100 secretion rate fell with both interventions, with no significant independent effect of ezetimibe. CONCLUSIONS Addition of ezetimibe to a moderate weight loss diet in obese subjects can significantly improve hepatic steatosis, inflammation, and LDL–apoB-100 metabolism.
The Chadwick Lecture ON MENTAL HYGIENE AND SHELL SHOCK DURING AND AFTER THE WAR
Authors: F. W. Mott
Journal: BMJ (1917)

MENTAL HYGIENE AND SHELL SHOCK.L V1 o1 Ba 39and spinal paralysis wlhich show a tendenev to an ascend- ing course lhave been in fact included in Landlry's paralysis, but it is now generally accepted that this.term slhould be restricted to a-condition wlhieh begins with a progressive paralysis of the lower limbs that rapidly ascends and involves the trunk muscles, later those of the arms.and as a rule leads to a fatal termination from respiratory palsy before the cranial nerves are affected.Objective sensory disturbances are also very slight or absent, and the sphincters are rarely involved.
Ursodeoxycholate stimulates Na+-H+ exchange in rat liver basolateral plasma membrane vesicles.
Authors: R H Moseley, N Ballatori, D J Smith, J L Boyer
Journal: Journal of Clinical Investigation (1987)

Na+:H+ and Cl-:HCO3- exchange are localized, respectively, to basolateral (blLPM) and canalicular (cLPM) rat liver plasma membranes. To determine whether these exchangers play a role in bile formation, we examined the effect of a choleretic agent, ursodeoxycholate (UDCA), on these exchange mechanisms. 22Na (1 mM) and 36Cl (5 mM) uptake was determined using outwardly directed H+ and HCO3- gradients, respectively. Preincubation of blLPM vesicles with UDCA (0-500 microM) resulted in a concentration-dependent increase in initial rates of amiloride-sensitive pH-driven Na+ uptake, with a maximal effect at 200 microM. UDCA (200 microM) increased Vmax from 23 +/- 2 (control) to 37 +/- 7 nmol/min per mg protein; apparent Km for Na+ was unchanged. Preincubation with tauroursodeoxycholate (200 microM), taurocholate (10-200 microM) or cholate, chenodeoxycholate, or deoxycholate (200 microM) had no effect on pH-driven Na+ uptake. UDCA (200 microM) had no effect on either membrane lipid fluidity, assessed by steady-state fluorescence polarization using the probes 1,6-diphenyl-1,3,5-hexatriene, 12-(9-anthroyloxy) stearic acid, and 2-(9-anthroyloxy) stearic acid (2-AS), or Na+,K+-ATPase activity in blLPM vesicles. In cLPM vesicles, UDCA (0-500 microM) had no stimulatory effect on initial rates of HCO3(-)-driven Cl- uptake. Enhanced basolateral Na+:H+ exchange activity, leading to intracellular HCO3- concentrations above equilibrium, may account for the bicarbonate-rich choleresis after UDCA infusion.
Phase II study of dolastatin-10 in patients with advanced non-small-cell lung cancer
Authors: L.M. Krug, V.A. Miller, G.P. Kalemkerian, M.J. Kraut, K.K. Ng, R.T. Heelan, B.A. Pizzo, W. Perez, N. McClean, M.G. Kris
Journal: Annals of Oncology (2000)
The Range of Adaptation by Collateral Vessels After Femoral Artery Occlusion
Authors: Inka Eitenmüller, Oscar Volger, Alexander Kluge, Kerstin Troidl, Miroslav Barancik, Wei-Jun Cai, Matthias Heil, Frederic Pipp, Silvia Fischer, Anton J.G. Horrevoets, Thomas Schmitz-Rixen, Wolfgang Schaper
Journal: Circulation Research (2006)

Natural adaptation to femoral artery occlusion in animals by collateral artery growth restores only approximately 35% of adenosine-recruitable maximal conductance (C(max)) probably because initially elevated fluid shear stress (FSS) quickly normalizes. We tested the hypothesis whether this deficit can be mended by artificially increasing FSS or whether anatomical restraints prevent complete restitution. We chronically increased FSS by draining the collateral flow directly into the venous system by a side-to-side anastomosis between the distal stump of the occluded femoral artery and the accompanying vein. After reclosure of the shunt collateral flow was measured at maximal vasodilatation. C(max) reached 100% already at day 7 and had, after 4 weeks, surpassed (2-fold) the C(max) of the normal vasculature before occlusion. Expression profiling showed upregulation of members of the Rho-pathway (RhoA, cofilin, focal adhesion kinase, vimentin) and the Rho-antagonist Fasudil markedly inhibited arteriogenesis. The activities of Ras and ERK-1,-2 were markedly increased in collateral vessels of the shunt experiment, and infusions of L-NAME and L-NNA strongly inhibited MAPK activity as well as shunt-induced arteriogenesis. Infusions of the peroxinitrite donor Sin-1 inhibited arteriogenesis. The radical scavengers urate, ebselen, SOD, and catalase had no effect. We conclude that increased FSS can overcome the anatomical restrictions of collateral arteries and is potentially able to completely restore maximal collateral conductance. Increased FSS activates the Ras-ERK-, the Rho-, and the NO- (but not the Akt-) pathway enabling collateral artery growth.
Dermatologic and Dental Aspects of the 2012 International Tuberous Sclerosis Complex Consensus Statements
Authors: Joyce M. C. Teng, Edward W. Cowen, Mari Wataya-Kaneda, Elizabeth S. Gosnell, Patricia M. Witman, Adelaide A. Hebert, Greg Mlynarczyk, Keyoumars Soltani, Thomas N. Darling
Journal: JAMA Dermatology (2014)

The 2012 International Tuberous Sclerosis Complex Clinical Consensus Conference was convened to update the last consensus statement in 1998. Skin and dental lesions are common in tuberous sclerosis complex (TSC) and are a frequent concern for patients. Recognition of these lesions is imperative for early diagnosis, given the treatment advances that may improve patient outcomes.
Evaluation of a Panel of Molecular Markers for the Diagnosis of Malignant Serous Effusions
Authors: Karine Passebosc-Faure, Guorong Li, Claude Lambert, Michèle Cottier, Anne Gentil-Perret, Pierre Fournel, Maurice Pérol, Christian Genin
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Our main goal was to evaluate a panel of molecular markers for the detection of cancer cells in serous effusions and to determine their value as an adjunctive reverse transcription-PCR (RT-PCR) test to cytologic examination. Experimental Design: One hundred fourteen serous effusions from 71 patients with tumors and 43 patients with benign diseases were subjected to RT-PCR for expression of carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (Ep-CAM), E-cadherin, mammaglobin, mucin 1 (MUC1) isoforms MUC1/REP, MUC1/Y, and MUC1/Z, calretinin, and Wilms' tumor 1 susceptibility gene. Results: CEA, Ep-CAM, E-cadherin, and mammaglobin were specifically expressed in malignant effusions. The sensitivity of RT-PCR in cytologically negative malignant effusions was 63.1% combining CEA and Ep-CAM (with 100% specificity) and reached 78.9% adding MUC1/Y or MUC1/Z (with 93% specificity). In the whole population of effusions, the combination of cytology with RT-PCR of CEA and Ep-CAM yielded a 90.1% sensitivity, a specificity and a positive predictive value of 100%, and a 86% negative predictive value for malignancy. Adding MUC1/Y or MUC1/Z to the panel, the sensitivity was 94.5% with 93% specificity, 95.7% PPV, and 90.9% negative predictive value. Moreover, CEA and mammaglobin were specifically expressed in epithelial malignancies, and mammaglobin was mainly expressed in effusions from breast carcinoma (97.3% of specificity). Conclusions: A combination of cytology and RT-PCR analysis of CEA and Ep-CAM significantly improved the detection sensitivity of tumor cells in serous effusions. RT-PCR analysis of CEA, Ep-CAM, and mammaglobin in serous effusions could be a beneficial adjunct to cytology for the diagnosis of malignancy.