tbuckley/cabot-search huggingface dataset:
Reiterative Survival Analyses of Total Therapy 2 for Multiple Myeloma Elucidate Follow-Up Time Dependency of Prognostic Variables and Treatment Arms
Authors: Bart Barlogie, Elias Anaissie, Frits van Rhee, John D. Shaughnessy, Jackie Szymonifka, Antje Hoering, Nathan Petty, John Crowley
Journal: Journal of Clinical Oncology (2010)

In Total Therapy 2, after randomly assigning 323 patients with myeloma to thalidomide and 345 to a control arm, no difference was observed in overall survival, with a median follow-up of 42 months, although at 72 months, survival was superior on the thalidomide arm in the one third exhibiting cytogenetic abnormalities (CA). After further follow-up of 87 months, we examined, in reiterative analyses, the effect of increasing time intervals on clinical outcomes relevant to baseline prognostic variables and treatment randomization.
A Comparison of Three Scales for Assessing Social Functioning in Primary Care
Authors: Myrna M. Weissman, Mark Olfson, Marc J. Gameroff, Adriana Feder, Milton Fuentes
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Assessment of functional status is increasingly important in clinical trials and outcome research. Although several scales for assessing functioning are widely used, they vary in coverage, and direct comparisons among them are rare. Comparative information is useful in guiding selection of appropriate scales for research applications. METHOD: Results from three scales that measure functioning—the Medical Outcomes Study 36-item Short-Form Health Survey, the Social Adjustment Scale Self-Report, and the Social Adaptation Self-Evaluation Scale—were compared in a consecutively selected sample of 211 patients coming to primary care. Patients also received psychiatric assessments. RESULTS: All three scales were acceptable to patients, showed few significant correlations with demographic variables, and were able to differentiate psychiatrically ill and well patients. Correlations among scales, even among scale items that assessed similar domains of functioning, were modest. CONCLUSIONS: Although all three scales are presumed to assess functional status, their item content and coverage differ. Selection of a scale requires a review of the scale items and consideration of research priorities and the characteristics of the study group. If functional status is a critical outcome measure, use of more than one scale may be necessary.
Chronic kidney disease in primary care
Authors: P. K. Mitra, J. R Bradley
Journal: Journal of the Royal Society of Medicine (2006)

It has been estimated that chronic kidney disease (CKD) affects about one in 200 of the population in the UK. There is an increased awareness of the need to identify patients in primary care with CKD at an earlier stage, so that treatments can be initiated to delay progression and prevent complications and appropriate nephrological referral can be made. In this article we will review how measures to identify patients with CKD can improve its management.
Role of Lung-marginated Monocytes in an <i>In Vivo</i> Mouse Model of Ventilator-induced Lung Injury
Authors: Michael R. Wilson, Kieran P. O'Dea, Da Zhang, Alexander D. Shearman, Nico van Rooijen, Masao Takata
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Recruited leukocytes play an important role in ventilator-induced lung injury, although studies have focused predominantly on neutrophils. Inflammatory subset Gr-1high monocytes are recruited to sites of inflammation and have been implicated in acute lung injury induced by systemic endotoxin.Objectives: To investigate the recruitment and role of Gr-1high monocytes in an in vivo mouse model of ventilator-induced lung injury.Methods: Anesthetized mice were ventilated with low or high stretch. Flow cytometry was used to quantify monocyte subset margination to the lungs, and to assess their in situ cellular activation in response to mechanical stretch. To investigate monocyte involvement in lung injury progression, a two-hit model was used, with a subclinical dose of lipopolysaccharide (intraperitoneal) given 2 hours prior to high-stretch ventilation. In some animals, monocytes were depleted using intravenous clodronate liposomes. Development of lung injury was assessed in ventilated animals by peak inspiratory pressure and respiratory system mechanics.Measurements and Main Results: High-stretch ventilation induced significant pulmonary margination of Gr-1high but not Gr-1low monocytes compared with nonventilated mice. These monocytes displayed increased activation status, with higher CD11b (vs. nonventilated mice) and lower L-selectin expression (vs. low-stretch ventilation). Lipopolysaccharide challenge led to enhanced lung margination of Gr-1high monocytes and neutrophils, and sensitized the lungs to high stretch–induced pulmonary edema. Clodronate-liposome pretreatment depleted lung monocytes (but not neutrophils) and significantly attenuated lung injury.Conclusions: High-stretch mechanical ventilation promotes pulmonary margination of activated Gr-1high monocytes, which play a role in the progression of ventilator-induced lung injury.
Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats
Authors: Jordi Ribera, Montse Pauta, Pedro Melgar-Lesmes, Sònia Tugues, Guillermo Fernández-Varo, Kara F Held, Guadalupe Soria, Raúl Tudela, Anna M Planas, Carlos Fernández-Hernando, Vicente Arroyo, Wladimiro Jiménez, Manuel Morales-Ruiz
Journal: Gut (2012)

<h3>Background and aim</h3> The lymphatic network plays a major role in maintaining tissue fluid homoeostasis. Therefore several pathological conditions associated with oedema formation result in deficient lymphatic function. However, the role of the lymphatic system in the pathogenesis of ascites and oedema formation in cirrhosis has not been fully clarified. The aim of this study was to investigate whether the inability of the lymphatic system to drain tissue exudate contributes to the oedema observed in cirrhosis. <h3>Methods</h3> Cirrhosis was induced in rats by CCl<sub>4</sub> inhalation. Lymphatic drainage was evaluated using fluorescent lymphangiography. Expression of endothelial nitric oxide synthase (eNOS) was measured in primary lymphatic endothelial cells (LyECs). Inhibition of eNOS activity in cirrhotic rats with ascites (CH) was carried out by L-N<sup>G</sup>-methyl-L-arginine (L-NMMA) treatment (0.5 mg/kg/day). <h3>Results</h3> The (CH) rats had impaired lymphatic drainage in the splanchnic and peripheral regions compared with the control (CT) rats. LyECs isolated from the CH rats showed a significant increase in eNOS and nitric oxide (NO) production. In addition, the lymphatic vessels of the CH rats showed a significant reduction in smooth muscle cell (SMC) coverage compared with the CT rats. CH rats treated with L-NMMA for 7 days showed a significant improvement in lymphatic drainage and a significant reduction in ascites volume, which were associated with increased plasma volume. This beneficial effect of L-NMMA inhibition was also associated with a significant increase in lymphatic SMC coverage. <h3>Conclusions</h3> The upregulation of eNOS in the LyECs of CH rats causes long-term lymphatic remodelling, which is characterised by a loss of SMC lymphatic coverage. The amelioration of this lymphatic abnormality by chronic eNOS inhibition results in improved lymphatic drainage and reduced ascites.
Enhanced ability of peripheral invariant natural killer T cells to produce IL-13 in chronic hepatitis C virus infection
Authors: Michiyo Inoue, Tatsuya Kanto, Hideki Miyatake, Ichiyo Itose, Masanori Miyazaki, Takayuki Yakushijin, Mitsuru Sakakibara, Noriyoshi Kuzushita, Naoki Hiramatsu, Tetsuo Takehara, Akinori Kasahara, Norio Hayashi
Journal: Journal of Hepatology (2006)
Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial
Authors: M. Rother, B. J Lavins, W. Kneer, K. Lehnhardt, E. J Seidel, S. Mazgareanu
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objective:</b> To compare epicutaneous ketoprofen in Transfersome (ultra-deformable vesicles, IDEA-033) versus oral celecoxib and placebo for relief of signs and symptoms in knee osteoarthritis. <b>Methods:</b> This was a multicentre, randomised, double-blind, controlled trial; 397 patients with knee osteoarthritis participated and 324 completed the trial. They were randomly assigned 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (n = 138), 100 mg oral celecoxib plus placebo gel (n = 132), or both placebo formulations (n = 127) twice daily for 6 weeks. Primary efficacy outcome measures were the changes from baseline to end of the study on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale, physical function subscale and patient global assessment (PGA) of response. <b>Results:</b> The mean WOMAC pain subscale scores in the intent to treat population were reduced by 18.2 (95% confidence interval −22.1 to −14.3), 20.3 (−24.3 to −16.2) and 9.9 (−13.9 to −5.8) in the IDEA-033, celecoxib and placebo groups, respectively, and the physical function subscale score by 14.6 (−18.1 to −11.0), 16.6 (−20.2 to −13.0) and 10.2 (−13.8 to −6.6), respectively. The mean PGA of response scores were 1.8 (1.6 to 2.1), 1.7 (1.5 to 1.9) and 1.3 (1.1 to 1.5), respectively. The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (p&lt;0.01) and PGA of response (p&lt;0.01). Gastrointestinal adverse events for IDEA-033 were similar to placebo. <b>Conclusion:</b> IDEA-033 is superior to placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis.
Comparison of colonoscopic performance between medical and nurse endoscopists: a non-inferiority randomised controlled study in Asia
Authors: Aric J Hui, James Y Lau, Phyllis P Y Lam, Alman O M Chui, Alice S H Fan, Thomas Y T Lam, Yee-kit Tse, Raymond S Y Tang, Siew C Ng, Justin C Y Wu, Jessica Y L Ching, Martin C S Wong, Francis K L Chan, Joseph Sung
Journal: Gut (2014)

<h3>Objective</h3> To test the hypothesis that trained nurse endoscopists are not inferior to medical endoscopists in finding adenomas during colonoscopy. <h3>Design</h3> This is a prospective, randomised, single-blind, non-inferiority study comparing nurses with medical endoscopists in performing screening colonoscopy. The nurse endoscopists had been trained according to the British Joint Advisory Group on GI Endoscopy curriculum and had completed at least 140 colonoscopic procedures prior to the study. The primary endpoint was the adenoma detection rate. Secondary endpoints included the caecal intubation rate, intubation time, complication rate, patient pain and satisfaction scores. <h3>Results</h3> We enrolled and analysed a total of 731 patients over a 15-month period. At least one adenoma was found in 159 (43.8%) of 363 patients by nurse endoscopists and 120 (32.7%) of 367 patients by medical endoscopists and a proportion difference of +11.1% compared with the medical endoscopists (95% CI 4.1% to 18.1%). The withdrawal time was, however, significantly longer among nurses (998 vs 575 s, p&lt;0.001). After adjusting for differences in a regression analysis, colonoscopy by nurses was associated with a lower adenoma detection rate (OR 0.475: 95% CI 0.311 to 0.725). Nurse endoscopists had a lower caecal intubation rate (97.3% vs 100%), received better pain and satisfaction scores and had a high rate of patient acceptance. <h3>Conclusions</h3> In this pragmatic trial, nurses can perform screening colonoscopy but require a longer procedural time to achieve a comparable adenoma detection rate as medical endoscopists. <h3>Trial registration number</h3> NCT01923155.
Limitations of serum values to estimate glomerular filtration rate during exercise
Authors: Jacques R Poortmans, Béatrice Gulbis, Edward De Bruyn, Stéphane Baudry, Alain Carpentier
Journal: British Journal of Sports Medicine (2012)

Objective Glomerular filtration rate (GFR) is part of routine medical practice for clinical assessment of kidney function in health and disease conditions, and is determined by measuring the clearance of creatinine (Cl-Crn) or estimated (eGFR) from equations using serum creatinine (Crn) or cystatin C (Cyst C). Crn and Cyst C methods obviate the need for urine collection but their reliability under non-resting conditions is uncertain. This study compared GFR determined by Cl-Crn, Crn and Cyst C methods under the conditions of rest and after exercise. Methods Twelve young male subjects performed a 30 min treadmill exercise at 80% of the maximal oxygen capacity. Venous blood samples and urine collections were collected before and after exercise and after recovery period. GFR rates were calculated from serum Crn and Cyst C equations, and Cl-Crn measured from serum and urine Crn output. Albumin was also determined for all samples. Results Under resting conditions, eGFR from Crn and Cyst C did not differ from Cl-Crn (p=0.39). Immediately after exercise, GFR decreased significantly, regardless of the method, but more so for Cl-Crn (−30.0%; p&lt;0.05) compared with Crn (−18.2%) and Cyst C (−19.8%). After the recovery period, GFR determined by Cl-Crn was returned to initial values whereas Crn and Cyst C remained reduced. Although eGFR methods accurately estimate GFR at rest, those methods underestimated the change in GFR after acute exercise. Conclusions These results indicate that exercise-induced changes in GFR should be determined by Cl-Crn method.
A Galectin-3–Dependent Pathway Upregulates Interleukin-6 in the Microenvironment of Human Neuroblastoma
Authors: Ayaka M. Silverman, Rie Nakata, Hiroyuki Shimada, Richard Sposto, Yves A. DeClerck
Journal: Cancer Research (2012)

Abstract Interleukin-6 (IL-6) is a pleiotropic cytokine with a broad range of physiologic and pathologic functions. Because in cancer, IL-6 contributes to a microenvironment that promotes tumor cell survival, angiogenesis, and inflammation, understanding the mechanism responsible for its production is important. In neuroblastoma, the second most common solid tumor in children, IL-6 is produced not by tumor cells but by stromal cells such as monocytes and bone marrow mesenchymal stem cells (BMMSC). Here we show that the production of IL-6 in BMMSCs is in part stimulated by galectin-3 binding protein (Gal-3BP) secreted by neuroblastoma cells. We identified a distal region of the IL-6 promoter that contains 3 CCATT/enhancer binding protein (C/EBP) binding domains involved in the transcriptional upregulation of IL-6 by Gal-3BP. Gal-3BP interacted with Galectin-3 (Gal-3) present in BMMSCs, and a Gal-3BP/Gal-3/Ras/MEK/ERK signaling pathway was responsible for the transcriptional upregulation of IL-6 in BMMSCs in which Gal-3 has a necessary function. In support of the role of this pathway in human neuroblastoma tumors, Gal-3BP was found to be present in tumor cells and in the adjacent extracellular matrix of 96% of 78 primary neuroblastoma tumor samples examined by immunohistochemistry. Considering the protumorigenic function of IL-6 in cancer, this tumor cell–stromal cell interactive pathway could be a target for anticancer therapy. Cancer Res; 72(9); 2228–38. ©2012 AACR.
Meningioma and schwannoma risk in adults in relation to family history of cancer
Authors: Deirdre A. Hill, Martha S. Linet, Peter M. Black, Howard A. Fine, Robert G. Selker, William R. Shapiro, Peter D. Inskip
Journal: Neuro-Oncology (2004)

Relatively little is known about factors that contribute to the development of meningioma and vestibular schwannoma, two intracranial nervous system tumors. We evaluated the risk of these tumors in relation to family history of malignant or benign tumors. Incident cases of meningioma (n = 197) or schwannoma (n = 96) were identified at three U.S. referral hospitals between June 1994 and August 1998. Controls (n = 799) admitted to the same hospitals for nonmalignant conditions were matched to cases on age, sex, race/ethnicity, hospital, and proximity of residence to hospital. We found that risk of meningioma was increased among persons reporting a family history of a benign brain tumor (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.0–21.0; n = 5) or melanoma (OR, 4.2; 95% CI, 1.2–15.0; n = 5). A family history of breast cancer was associated with an elevated meningioma risk among participants aged 18 to 49 years (OR, 3.9; 95% CI, 1.4–11.0; n = 8) but a reduced risk among older respondents (OR, 0.2; 95% CI, 0.1–0.7; n = 3). Family history of cancer did not differ between schwannoma cases and controls, although the statistical power to detect associations was limited. Some relative risk estimates were based on a small number of observations and may have arisen by chance. Inheritance of predisposing genes, shared environmental factors, or both within families with a history of benign brain tumors, melanoma, or possibly breast cancer may be related to altered meningioma risk.
Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts.
Authors: A Calderone, C M Thaik, N Takahashi, D L Chang, W S Colucci
Journal: Journal of Clinical Investigation (1998)

This study tested the hypothesis that nitric oxide (NO) and atrial natriuretic peptide (ANP) can attenuate the effects of adrenergic agonists on the growth of cardiac myocytes and fibroblasts. In ventricular cells cultured from neonatal rat heart, ANP and the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) caused concentration-dependent decreases in the norepinephrine (NE)-stimulated incorporation of [3H]leucine in myocytes and [3H]thymidine in fibroblasts. In myocytes, the NO synthase inhibitor NG-monomethyl-L-arginine potentiated NE-stimulated [3H]leucine incorporation. In both cell types, ANP and SNAP increased intracellular cGMP levels, and their growth-suppressing effects were mimicked by the cGMP analogue 8-bromo-cGMP. Furthermore, in myocytes, 8-bromo-cGMP attenuated the alpha1-adrenergic receptor-stimulated increases in c-fos. Likewise, ANP and 8-bromo-cGMP attenuated the alpha1-adrenergic receptor- stimulated increase in prepro-ANP mRNA and the alpha1-adrenergic receptor-stimulated decrease in sarcoplasmic reticulum calcium ATPase mRNA. The L-type Ca2+ channel blockers verapamil and nifedipine inhibited NE-stimulated incorporation of [3H]leucine in myocytes and [3H]thymidine in fibroblasts, and these effects were not additive with those of ANP, SNAP, or 8-bromo-cGMP. In myocytes, the Ca2+ channel agonist BAY K8644 caused an increase in [3H]leucine incorporation which was inhibited by ANP. These findings indicate that NO and ANP can attenuate the effects of NE on the growth of cardiac myocytes and fibroblasts, most likely by a cGMP-mediated inhibition of NE-stimulated Ca2+ influx.
In Vivo HIF-Mediated Reductive Carboxylation Is Regulated by Citrate Levels and Sensitizes VHL-Deficient Cells to Glutamine Deprivation
Authors: Paulo A. Gameiro, Juanjuan Yang, Ana M. Metelo, Rocio Pérez-Carro, Rania Baker, Zongwei Wang, Alexandra Arreola, W. Kimryn Rathmell, Aria Olumi, Pilar López-Larrubia, Gregory Stephanopoulos, Othon Iliopoulos
Journal: Cell Metabolism (2013)
Specific tolerance to neural allografts induced with an antibody to the interleukin 2 receptor.
Authors: M J Wood, D J Sloan, M J Dallman, H M Charlton
Journal: The Journal of Experimental Medicine (1993)

Despite considerable evidence documenting the central nervous system as a site of immunological privilege, immune responses do occur within the brain and neural allografts between major histocompatibility complexes (MHC) and minor antigen incompatible rat strains may be rejected. The survival of completely MHC incompatible neural allografts has been found to be prolonged indefinitely after administration of a monoclonal antibody (mAb) to the interleukin 2 receptor (IL-2R) for 10 d after transplantation. Here we present evidence that rats with long-term surviving lateral ventricular neural allografts, after anti-IL-2R treatment, accept subsequent neural allografts from the same donor strain, placed in a peripheral nonprivileged site, but rapidly reject third-party grafts. Thus, treatment with a mAb to the p55 chain of the IL-2R has resulted in the specific acceptance of second grafts of fully allogeneic neural tissue. These results suggest that ongoing interaction between elements of the host immune system and alloantigen within the brain maintains the tolerant state and furthermore, that interruption of signaling through the IL-2R may be important in allospecific tolerance induction.
Toxicity and health effects of selected organotin compounds: a review.
Authors: R D Kimbrough
Journal: Environmental Health Perspectives (1976)

The toxicity of selected tin compounds is reviewed. Over the years, a variety of uses has been found for organic and inorganic tin compounds, as fungicides, as stablizers in plastics, moluscicides, and miticides; they have also been suggested as insect chemosterilants and for other industrial uses. Many of these products are unpalatable when mixed into diets and have been suggested as rodent repellents. Inhaling tin as dust or fumes may cause a benign pneumoconiosis in exposed workers. The organotin compounds can be divided into alkyltin and aryltin compounds. The trimethyl and triethyltin compounds are well absorbed from the gastrointestinal tract and are the most toxic in this group. Triethyltin particularly produces status spongiosus of the white matter of the central nervous system. Most of the other alkyl and aryl tin compounds are poorly absorbed from the gastrointestinal tract, and are less toxic when given orally than when given parentally. Only one compound, tricyclohexyltin hydroxide, is now registered by the Environmental Protection Agency as a miticide. This product produces skin irritation in rabbits. Studies should be conducted to determine whether it causes contact dermatitis in humans.
Differences in Atherosclerotic Plaque Burden and Morphology Between Type 1 and 2 Diabetes as Assessed by Multislice Computed Tomography
Authors: Roxana Djaberi, Joanne D. Schuijf, Eric Boersma, Lucia J.M. Kroft, Alberto M. Pereira, Johannes A. Romijn, Arthur J. Scholte, J. Wouter Jukema, Jeroen J. Bax
Journal: Diabetes Care (2009)

OBJECTIVE It is unclear whether the coronary atherosclerotic plaque burden is similar in patients with type 1 and type 2 diabetes. By using multislice computed tomography (MSCT), the presence, degree, and morphology of coronary artery disease (CAD) in patients with type 1 and type 2 diabetes were compared. RESEARCH DESIGN AND METHODS Prospectively, coronary artery calcium (CAC) scoring and MSCT coronary angiography were performed in 135 asymptomatic patients (65 patients with type 1 diabetes and 70 patients with type 2 diabetes). The presence and extent of coronary atherosclerosis as well as plaque phenotype were assessed and compared between groups. RESULTS No difference was observed in average CAC score (217 ± 530 vs. 174 ± 361) or in the prevalence of coronary atherosclerosis (65% vs. 71%) in patients with type 1 and type 2 diabetes. However, the prevalence of obstructive atherosclerosis was higher in patients with type 2 diabetes (n = 24; 34%) compared with that in patients with type 1 diabetes (n = 11; 17%) (P = 0.02). In addition, a higher mean number of atherosclerotic and obstructive plaques was observed in patients with type 2 diabetes. In addition, the percentage of noncalcified plaques was higher in patients with type 2 (66%) versus type 1 diabetes (27%) (P &amp;lt; 0.001), resulting in a higher plaque burden for each CAC score compared with that in type 1 diabetic patients. CONCLUSIONS Although CAC scores and the prevalence of coronary atherosclerosis were similar between patients with type 1 and type 2 diabetes, CAD was more extensive in the latter. Also, a relatively higher proportion of noncalcified plaques was observed in patients with type 2 diabetes. These observations may be valuable in the development of targeted management strategies adapted to diabetes type.