tbuckley/cabot-search huggingface dataset:
High Prevalence of Microvascular Complications in Adults With Type 1 Diabetes and Newly Diagnosed Celiac Disease
Authors: John S. Leeds, Andrew D. Hopper, Marios Hadjivassiliou, Solomon Tesfaye, David S. Sanders
Journal: Diabetes Care (2011)

The implications of celiac disease (CD) in adult patients with type 1 diabetes are unknown, with respect to diabetes-related outcomes including glycemic control, lipids, microvascular complications, quality of life, and the effect of a gluten-free diet (GFD). We identified CD in adults with type 1 diabetes and investigated the effect of a GFD on diabetes-related complications.This was a case-control study conducted at a U.K. teaching hospital. Patients with type 1 diabetes aged >16 years (n = 1,000) were assessed for CD. HbA(1c), lipid profile, quality of life, retinopathy stage, nephropathy stage, and degree of neuropathy before and after 1 year on a GFD were assessed.The prevalence of CD was 33 per 1,000 subjects (3.3% [95% CI 2.3-4.6]). At diagnosis of CD, adult type 1 diabetic patients had worse glycemic control (8.2 vs. 7.5%, P = 0.05), lower total cholesterol (4.1 vs. 4.9, P = 0.014), lower HDL cholesterol (1.1 vs. 1.6, P = 0.017), and a higher prevalence of retinopathy (58.3 vs. 25%, P = 0.02), nephropathy (41.6 vs. 4.2%, P = 0.009), and peripheral neuropathy (41.6 vs. 16.6%, P = 0.11). There was no difference in quality of life (P > 0.1). After 1 year on a GFD, only the lipid profile improved overall, but in adherent individuals HbA(1c) and markers for nephropathy improved.Adults with undetected CD and type 1 diabetes have worse glycemic control and a higher prevalence of retinopathy and nephropathy. Treatment with a GFD for 1 year is safe in adults with type 1 diabetes and does not have a negative impact on the quality of life.
Ultrasound Morphology Criteria Predict Metastatic Disease of the Sentinel Nodes in Patients With Melanoma
Authors: Christiane Voit, Alexander C.J. Van Akkooi, Gregor Schäfer-Hesterberg, Alfred Schoengen, Katharina Kowalczyk, Joachim C. Roewert, Wolfram Sterry, Alexander M.M. Eggermont
Journal: Journal of Clinical Oncology (2010)

PURPOSE We have shown that ultrasound (US) -guided fine needle aspiration cytology (FNAC) can accurately identify the sentinel node (SN). Moreover, US-guided FNAC before the surgical SN procedure could identify up to 65% of all SN metastases. Herein we analyzed in detail the different US morphologic patterns of SN metastases. PATIENTS AND METHODS From July 2001 to December 2007, a total of 650 patients with melanoma scheduled for sentinel lymph node dissection were examined. We present the first 400 with sufficient follow-up (mean 40, median 39 months). Several morphologic characteristics were scored. In case of suspicious/clearly malignant US patterns a FNAC was performed. The final histology was considered the gold standard. Results Median Breslow was 1.8 mm. The sensitivity and positive predictive value of the most important factors were: peripheral perfusion (PP) present (77% and 52%, respectively), loss of central echoes (LCE; 60% and 65% respectively), and balloon shape (BS; 30% and 96% respectively). Together these factors have a sensitivity of 82% and PPV of 52% (P < .001). PP identified more patients with lower volume disease. PP and combined BS and LCE were independent prognostic factors for survival (hazard ratio, 2.19; P < .015; and hazard ratio, 5.50; P < .001, respectively). CONCLUSION Preoperative US and FNAC can identify 65% of SN metastases and thus reduce the need for surgical SN procedures. Peripheral perfusion is an early sign of involvement and of crucial importance to achieve a high identification rate. Balloon shape and loss of central echoes are late signs of metastases. We recommend US evaluation to identify those patients, who can directly proceed to a complete lymph node dissection after a positive US-guided FNAC of the SN.
Post–lung Transplant Bronchiolitis Obliterans Syndrome (BOS) Is Characterized by Increased Exhaled Nitric Oxide Levels and Epithelial Inducible Nitric Oxide Synthase
Authors: ELI GABBAY, E. HAYDN WALTERS, BERNADETTE ORSIDA, HELEN WHITFORD, CHRISTOPHER WARD, TOM C. KOTSIMBOS, GREGORY I. SNELL, TREVOR J. WILLIAMS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

In conditions characterized by airway inflammation, exhaled nitric oxide (eNO) levels are increased. Post-lung transplant bronchiolitis obliterans syndrome (BOS) is characterized by airway inflammation and development of progressive airway narrowing and fibrosis. We have previously shown that in stable lung transplant recipients (LTR), mean eNO levels were not elevated but were still related to the degree of airway neutrophilia within the group. The hypothesis now tested is that in BOS, eNO levels are increased in association with even greater airway neutrophilia and enhanced expression of inducible (iNOS) nitric oxide synthase in the bronchial epithelium. We determined eNO levels in 40 LTR in four groups: well and "stable": LTR (n = 20), BOS (n = 8), bacterial airway infection (BI, n = 6), and acute rejection (AR, n = 6). Following bronchoscopic sampling, we performed a quantitative assessment of iNOS and constitutive nitric oxide synthase (cNOS) expression in endobronchial biopsies by immunohistochemistry. Mean ± SEM eNO levels in BOS and BI were significantly higher than in stable LTR (20 ± 1.2 parts per billion [ppb] and 24.7 ± 1.7 ppb versus 12.5 ± 0.9 ppb; p < 0.01 for both). In AR, eNO levels (13.4 ppb ± 0.5) were not different in stable LTR (p = 0.34). When compared with stable LTR, there was increased expression of iNOS in the bronchial epithelium and generally in the lamina propria (LP) in patients with BOS and BI. In AR, iNOS expression was increased but only in the LP in a perivascular distribution. Expression of cNOS was reduced in BOS but not in BI and AR compared with the stable group. Using regression analysis, only iNOS expression in the bronchial epithelium (r2 = 0.77; p < 0.0001) and %BAL neutrophils (r2 = 0.79; p < 0.0001) were positively related to eNO in stable LTR and BOS. We conclude that epithelial iNOS appears to be the major source of eNO. Exhaled NO levels also appear to reflect the degree of airway neutrophilia in both stable LTR and BOS groups. This suggests that serial eNO measurements may be able to predict the early development of BOS.
Novel insights into ammonia-mediated neurotoxicity pointing to potential new therapeutic strategies
Authors: Anna Hadjihambi, Christopher F. Rose, Rajiv Jalan, Rangroo V Thrane, A S Thrane, F Wang, M L Cotrina, N A Smith, M Chen
Journal: Hepatology (2014)

Abstract Ammonia is a ubiquitous waste product of protein metabolism that can accumulate in numerous metabolic disorders, causing neurological dysfunction ranging from cognitive impairment to tremor, ataxia, seizures, coma and death. The brain is especially vulnerable to ammonia as it readily crosses the blood-brain barrier in its gaseous form, NH 3 , and rapidly saturates its principal removal pathway located in astrocytes. Thus, we wanted to determine how astrocytes contribute to the initial deterioration of neurological functions characteristic of hyperammonemia in vivo . Using a combination of two-photon imaging and electrophysiology in awake head-restrained mice, we show that ammonia rapidly compromises astrocyte potassium buffering, increasing extracellular potassium concentration and overactivating the Na + -K + −2Cl – cotransporter isoform 1 (NKCC1) in neurons. The consequent depolarization of the neuronal GABA reversal potential (E GABA ) selectively impairs cortical inhibitory networks. Genetic deletion of NKCC1 or inhibition of it with the clinically used diuretic bumetanide potently suppresses ammonia-induced neurological dysfunction. We did not observe astrocyte swelling or brain edema in the acute phase, calling into question current concepts regarding the neurotoxic effects of ammonia. Instead, our findings identify failure of potassium buffering in astrocytes as a crucial mechanism in ammonia neurotoxicity and demonstrate the therapeutic potential of blocking this pathway by inhibiting NKCC1.
Dapagliflozin Monotherapy in Type 2 Diabetic Patients With Inadequate Glycemic Control by Diet and Exercise
Authors: Ele Ferrannini, Silvia Jimenez Ramos, Afshin Salsali, Weihua Tang, James F. List
Journal: Diabetes Care (2010)

OBJECTIVE Dapagliflozin, a highly selective inhibitor of the renal sodium-glucose cotransporter-2, increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner. We evaluated the efficacy and safety of dapagliflozin in treatment-naive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS This was a 24-week parallel-group, double-blind, placebo-controlled phase 3 trial. Patients with A1C 7.0–10% (n = 485) were randomly assigned to one of seven arms to receive once-daily placebo or 2.5, 5, or 10 mg dapagliflozin once daily in the morning (main cohort) or evening (exploratory cohort). Patients with A1C 10.1–12% (high-A1C exploratory cohort; n = 73) were randomly assigned 1:1 to receive blinded treatment with a morning dose of 5 or 10 mg/day dapagliflozin. The primary end point was change from baseline in A1C in the main cohort, statistically tested using an ANCOVA. RESULTS In the main cohort, mean A1C changes from baseline at week 24 were −0.23% with placebo and −0.58, −0.77 (P = 0.0005 vs. placebo), and −0.89% (P &amp;lt; 0.0001 vs. placebo) with 2.5, 5, and 10 mg dapagliflozin, respectively. Signs, symptoms, and other reports suggestive of urinary tract infections and genital infection were more frequently noted in the dapagliflozin arms. There were no major episodes of hypoglycemia. Data from exploratory cohorts were consistent with these results. CONCLUSIONS Dapagliflozin lowered hyperglycemia in treatment-naive patients with newly diagnosed type 2 diabetes. The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes.
Intensive care in patients with lung cancer: a multinational study
Authors: M. Soares, A.-C. Toffart, J.-F. Timsit, G. Burghi, C. Irrazábal, N. Pattison, E. Tobar, B.F.C. Almeida, U.V.A. Silva, L.C.P. Azevedo, A. Rabbat, C. Lamer, A. Parrot, V.C. Souza-Dantas, F. Wallet, F. Blot, G. Bourdin, C. Piras, J. Delemazure, M. Durand, D. Tejera, J.I.F. Salluh, E. Azoulay
Journal: Annals of Oncology (2014)
Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22
Authors: E. Evangelou, A. M. Valdes, H. J. M. Kerkhof, U. Styrkarsdottir, Y. Zhu, I. Meulenbelt, R. J. Lories, F. B. Karassa, P. Tylzanowski, S. D. Bos, T. Akune, N. K. Arden, A. Carr, K. Chapman, L. A. Cupples, J. Dai, P. Deloukas, M. Doherty, S. Doherty, G. Engstrom, A. Gonzalez, B. V. Halldorsson, C. L. Hammond, D. J. Hart, H. Helgadottir, A. Hofman, S. Ikegawa, T. Ingvarsson, Q. Jiang, H. Jonsson, J. Kaprio, H. Kawaguchi, K. Kisand, M. Kloppenburg, U. M. Kujala, L. S. Lohmander, J. Loughlin, F. P. Luyten, A. Mabuchi, A. McCaskie, M. Nakajima, P. M. Nilsson, N. Nishida, W. E. R. Ollier, K. Panoutsopoulou, T. van de Putte, S. H. Ralston, F. Rivadeneira, J. Saarela, S. Schulte-Merker, D. Shi, P. E. Slagboom, A. Sudo, A. Tamm, A. Tamm, G. Thorleifsson, U. Thorsteinsdottir, A. Tsezou, G. A. Wallis, J. M. Wilkinson, N. Yoshimura, E. Zeggini, G. Zhai, F. Zhang, I. Jonsdottir, A. G. Uitterlinden, D. T. Felson, J. B. van Meurs, K. Stefansson, J. P. A. Ioannidis, T. D. Spector
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component. <h3>Methods</h3> A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets. <h3>Results</h3> With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p=9.2×10<sup>−9</sup>), thereby confirming its role as a susceptibility locus for OA. <h3>Conclusion</h3> The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: <i>PRKAR2B</i> (protein kinase, cAMP-dependent, regulatory, type II, β), <i>HPB1</i> (HMG-box transcription factor 1), <i>COG5</i> (component of oligomeric golgi complex 5<i>), GPR22</i> (G protein-coupled receptor 22), <i>DUS4L</i> (dihydrouridine synthase 4-like) and <i>BCAP29</i> (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
Systematic review of the incidence and consequences of uterine rupture in women with previous caesarean section
Authors: Jeanne-Marie Guise, Marian S McDonagh, Patricia Osterweil, Peggy Nygren, Benjamin K S Chan, Mark Helfand
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To evaluate the incidence and consequences of uterine rupture in women who have had a delivery by caesarean section. <b>Design</b> Systematic review. <b>Data sources</b> Medline, HealthSTAR, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Centre for Reviews and Dissemination, reference lists, and national experts. Studies in all languages were eligible if published in full. <b>Review methods</b> Methodological quality was evaluated for each study by using criteria from the United States Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination. Uterine rupture was categorised as asymptomatic or symptomatic. <b>Results</b> We reviewed 568 full text articles to identify 71 potentially eligible studies, 21 of which were rated at least fair in quality. Compared with elective repeat caesarean delivery, trial of labour increased the risk of uterine rupture by 2.7 (95% confidence interval 0.73 to 4.73) per 1000 cases. No maternal deaths were related to rupture. For women attempting vaginal delivery, the additional risk of perinatal death from rupture of a uterine scar was 1.4 (0 to 9.8) per 10 000 and the additional risk of hysterectomy was 3.4 (0 to 12.6) per 10 000. The rates of asymptomatic uterine rupture in trial of labour and elective repeat caesarean did not differ significantly. <b>Conclusions</b> Although the literature on uterine rupture is imprecise and inconsistent, existing studies indicate that 370 (213 to 1370) elective caesarean deliveries would need to be performed to prevent one symptomatic uterine rupture.
Remarkable activity of novel agents bortezomib and thalidomide in patients not responding to donor lymphocyte infusions following nonmyeloablative allogeneic stem cell transplantation in multiple myeloma
Authors: Niels W. C. J. van de Donk, Nicolaus Kröger, Ute Hegenbart, Paolo Corradini, Jesus F. San Miguel, Hartmut Goldschmidt, Jose A. Perez-Simon, Mark Zijlmans, Reinier A. Raymakers, Vittorio Montefusco, Francis A. Ayuk, Marinus H. J. van Oers, Arnon Nagler, Leo F. Verdonck, Henk M. Lokhorst
Journal: Blood (2006)
Excess nitric oxide in ulcerative colitis may be generated by nitric oxide synthase independent pathways
Authors: Z ZHANG, D P NAUGHTON, E CARTY, D S RAMPTON
Journal: Gut (1999)

Editor,—Kimura et al ( Gut 1998; 42 :180–7) provide further data in support of the proposal that production of nitric oxide (NO) in ulcerative colitis (UC) is ascribable primarily to the action of inducible NO synthase (NOS) on l-arginine.1-3 

This reaction relies on molecular oxygen as a substrate (fig1).4 However, the Po 2 of gas in the normal colon is low (sometimes only 1–2 mm Hg), not only as a result of bacterial utilisation of oxygen, but also reflecting mucosal hypoxia as a result of cellular metabolism and counter current diffusion of oxygen between mucosal capillaries.5 In active UC, mucosal ischaemia and conversion of oxygen to reactive oxygen …
Development of Clinical Practice Guidelines
Authors: Steven D. Hollon, Patricia A. Areán, Michelle G. Craske, Kermit A. Crawford, Daniel R. Kivlahan, Jeffrey J. Magnavita, Thomas H. Ollendick, Thomas L. Sexton, Bonnie Spring, Lynn F. Bufka, Daniel I. Galper, Howard Kurtzman
Journal: Annual Review of Clinical Psychology (2014)

Clinical practice guidelines (CPGs) are intended to improve mental, behavioral, and physical health by promoting clinical practices that are based on the best available evidence. The American Psychological Association (APA) is committed to generating patient-focused CPGs that are scientifically sound, clinically useful, and informative for psychologists, other health professionals, training programs, policy makers, and the public. The Institute of Medicine (IOM) 2011 standards for generating CPGs represent current best practices in the field. These standards involve multidisciplinary guideline development panels charged with generating recommendations based on comprehensive systematic reviews of the evidence. The IOM standards will guide the APA as it generates CPGs that can be used to inform the general public and the practice community regarding the benefits and harms of various treatment options. CPG recommendations are advisory rather than compulsory. When used appropriately, high-quality guidelines can facilitate shared decision making and identify gaps in knowledge.
Chronic treatment with interleukin-1 beta induces coronary intimal lesions and vasospastic responses in pigs in vivo. The role of platelet-derived growth factor.
Authors: H Shimokawa, A Ito, Y Fukumoto, T Kadokami, R Nakaike, M Sakata, T Takayanagi, K Egashira, A Takeshita
Journal: Journal of Clinical Investigation (1996)

Studies in vitro have suggested that inflammatory cytokines may play an important role in the pathogenesis of atherosclerosis. However, little is known about their effects in vivo. Thus, the present study was designed to determine in vivo what histological and functional changes may be induced by chronic treatment with IL-1 beta, one of the major inflammatory cytokines, and also to clarify what mechanisms are involved in those changes. Under aseptic conditions, proximal segments of the left porcine coronary arteries were gently wrapped with cotton mesh absorbing Sepharose beads either with or without recombinant human IL-1 beta. From 1 to 4 wk after the operation, coronary vasospastic responses to intracoronary serotonin or histamine were noted at the IL-1 beta-treated site but not at the control site. Histologically, intimal thickening was greater at the IL-1 beta-treated site than at the control site. Those functional and histological changes induced by the chronic treatment with IL-1 beta were significantly inhibited by the simultaneous treatment with a neutralizing antibody to either IL-1 beta or PDGF. These results indicate that chronic treatment with Il-1 beta induces coronary intimal lesions and vasospastic responses in porcine coronary arteries in vivo and also suggest that these changes are substantially mediated by PDGF.
THE EGESTION OF PHAGOCYTIZED PARTICLES BY LEUKOCYTES
Authors: Armine T. Wilson
Journal: The Journal of Experimental Medicine (1953)

Streptococci that were phagocytized by human or mouse leukocytes were usually enclosed in a digestive vacuole. At times the vacuole emptied itself, discharging the cocci to the outside. Whether the egested streptococci then multiplied in the extracellular environment appeared to depend upon how long they had been in the vacuole. The phenomenon of egestion also involves particles other than bacteria, as shown by observation of an erythrocyte that was phagocytized by a human leukocyte and was hemolyzed intracellularly, forming a cell ghost that was then egested.
Direct Evidence for Tumor Necrosis Factor-α Signaling in Arteriogenesis
Authors: Imo E. Hoefer, Niels van Royen, John E. Rectenwald, Elizabeth J. Bray, Zaher Abouhamze, Lyle L. Moldawer, Michiel Voskuil, Jan J. Piek, Ivo R. Buschmann, C. Keith Ozaki
Journal: Circulation (2002)

Background — Arteriogenesis serves as an efficient mechanism for flow restoration after arterial occlusion. This process is associated with inflammatory mediators such as tumor necrosis factor-α (TNF-α), although their role in arteriogenesis remains unclear. We hypothesized that arteriogenesis is reduced in mice lacking functional TNF-α or p55 receptor. To test this hypothesis, we developed a novel microsphere-based murine model of hindlimb perfusion measurement. Methods and Results — Unilateral femoral arteries of nude (n=9), TNF-α −/− (n=9), TNF-α receptor p55 −/− (n=8), and p75 −/− (n=8) mice as well as their appropriate genetic background controls were occluded. The nude mice underwent laser Doppler hindlimb flux measurements preoperatively, postoperatively, and after 7 days. Seven days after ligation, all animals underwent tissue perfusion determinations using fluorescent microspheres. Laser Doppler findings confirmed acute decrease in flux with falsely normal values after 1 week. Microsphere results from control mice showed perfusion restoration to values ≈50% of normal within 7 days. TNF-α −/− mice demonstrated a significant reduction (45.1%) in collateral artery perfusion compared with controls (TNF-α −/− 22.4±5.1% versus B6x129 49.7±9.3%; P &lt;0.01). p55 −/− mice exhibited an almost identical 45.8% reduction in collateral artery formation (p55 −/− 28.3±4.3% versus C57BL/6J 61.8±9.1%; P &lt;0.01), whereas p75 −/− mice were equivalent to controls (p75 −/− 54.5±5.5%; P =0.13). Conclusions — Microsphere techniques in mice offer a tool for the molecular dissection of arteriogenesis mechanisms. These results suggest that TNF-α positively modulates arteriogenesis probably via signaling through its p55 receptor.
Phase II of oral gimatecan in patients with recurrent epithelial ovarian, fallopian tube or peritoneal cancer, previously treated with platinum and taxanes
Authors: S. Pecorelli, I. Ray-Coquard, O. Tredan, N. Colombo, G. Parma, G. Tisi, D. Katsaròs, C. Lhommé, A.A. Lissoni, J.B. Vermorken, A. du Bois, A. Poveda, L. Frigerio, P. Barbieri, P. Carminati, S. Brienza, J.P. Guastalla
Journal: Annals of Oncology (2009)
Joint NCCTG and NABTC prognostic factors analysis for high-grade recurrent glioma
Authors: W. Wu, K. R. Lamborn, J. C. Buckner, P. J. Novotny, S. M. Chang, J. R. O'Fallon, K. A. Jaeckle, M. D. Prados
Journal: Neuro-Oncology (2009)

The purpose of this study is to determine prognostic factors in patients with high-grade recurrent glioma for 3 outcome variables (overall survival, progression-free survival [PFS], and PFS rate 6 months after study registration [PFS6]). Data from 15 North Central Cancer Treatment Group (NCCTG) trials (n = 469, 1980–2004) and 12 North American Brain Tumor Consortium (NABTC) trials (n = 596, 1998–2002) were included. Eighteen prognostic variables were considered including type of treatment center (community/academic) and initial low-grade histology (yes/no). Recursive partitioning analysis (RPA), Cox proportional hazards, and logistic regression models with bootstrap resampling were used to identify prognostic variables. Longer survival was associated with last known grade (Grade) of III, younger age, ECOG performance score (PS) of 0, shorter time from initial diagnosis (DxTime), and no baseline steroid use. Factors associated with longer PFS were Grade III and shorter DxTime. For patients without temozolomide as part of the treatment regimen, the only factor associated with better PFS6 was Grade III, although DxTime was important in RPA and PS was important in logistic regression. Grade was the most important prognostic factor for all three endpoints regardless of the statistical method used. Other important variables for one or more endpoints included age, PS, and DxTime. Neither type of treatment center nor initial low-grade histology was identified as a major predictor for any endpoint.