tbuckley/cabot-search huggingface dataset:
Physiological responses to linear treadmill and cycle ergometer exercise in COPD
Authors: D. Hsia, R. Casaburi, A. Pradhan, E. Torres, J. Porszasz
Journal: European Respiratory Journal (2009)

Incremental cardiopulmonary exercise testing work rate ideally increases linearly to the subject’s tolerance within approximately 10 min. Widely used treadmill protocols often yield shorter exercise times in debilitated patients. We compared a recently described treadmill protocol featuring linear work rate increase, weight adjustments and a priori exercise tolerance estimates with standard cycle and treadmill protocols. We also compared treadmill and cycle responses to examine mechanisms of oxyhaemoglobin desaturation differences. In total, 16 subjects with chronic obstructive pulmonary disease (COPD; mean± sd forced expiratory volume in 1 s of 36.5±10.9% predicted) performed incremental exercise using cycle, linear treadmill and modified Bruce protocols. Initial linear treadmill speed and grade yielded oxygen uptake ( V ′ O 2 ) similar to cycle unloaded pedalling; Bruce protocol first stage elicited much higher V ′ O 2 . Exercise duration was much shorter in Bruce than in cycle or linear treadmill protocols. At peak exercise, greater desaturation was noted in linear treadmill and Bruce protocols compared with cycle (-8.9±4.9 versus -8.5±4.7 versus -3.7±3.3%; p&lt;0.001); at iso- V ′ O 2 values this difference widened as exercise proceeded. Iso- V ′ O 2 desaturation differences were largely related to higher ventilatory response to cycle than to treadmill exercise. The linear incremental treadmill protocol generates responses similar to cycle ergometry in severe COPD. However, cycle ergometry elicits less desaturation than does ambulation, making the linear treadmill protocol advantageous when evaluating COPD patients.
Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy?
Authors: Benjamin John Floyd Dean, Sarah Louise Franklin, Richard J Murphy, Muhammad K Javaid, Andrew Jonathan Carr
Journal: British Journal of Sports Medicine (2014)

Background Glucocorticoid injection (GCI) and surgical rotator cuff repair are two widely used treatments for rotator cuff tendinopathy. Little is known about the way in which medical and surgical treatments affect the human rotator cuff tendon in vivo. We assessed the histological and immunohistochemical effects of these common treatments on the rotator cuff tendon. Study design Controlled laboratory study. Methods Supraspinatus tendon biopsies were taken before and after treatment from 12 patients undergoing GCI and 8 patients undergoing surgical rotator cuff repair. All patients were symptomatic and none of the patients undergoing local GCI had full thickness tears of the rotator cuff. The tendon tissue was then analysed using histological techniques and immunohistochemistry. Results There was a significant increase in nuclei count and vascularity after rotator cuff repair and not after GCI (both p=0.008). Hypoxia inducible factor 1α (HIF-1α) and cell proliferation were only increased after rotator cuff repair (both p=0.03) and not GCI. The ionotropic N -methyl- d -aspartate receptor 1 (NMDAR1) glutamate receptor was only increased after GCI and not rotator cuff repair (p=0.016). An increase in glutamate was seen in both groups following treatment (both p=0.04), while an increase in the receptor metabotropic glutamate receptor 7 (mGluR7) was only seen after rotator cuff repair (p=0.016). Conclusions The increases in cell proliferation, vascularity and HIF-1α after surgical rotator cuff repair appear consistent with a proliferative healing response, and these features are not seen after GCI. The increase in the glutamate receptor NMDAR1 after GCI raises concerns about the potential excitotoxic tendon damage that may result from this common treatment.
Orchidectomy increases the formation of prostanoids and modulates their role in the acetylcholine-induced relaxation in the rat aorta
Authors: A. Martorell, J. Blanco-Rivero, R. Aras-Lopez, A. Sagredo, G. Balfagon, M. Ferrer
Journal: Cardiovascular Research (2007)

This study examines the effect of endogenous male sex hormones on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF(2 alpha), and PGE I2 release, as well as their role in acetylcholine (ACh)-mediated relaxation in the aorta.Aortic segments from orchidectomized and control male Sprague-Dawley rats were used to measure COX-2 protein expression. ACh-induced relaxation of these segments was also determined in the absence and presence of the COX-2 inhibitor NS-398, the TXA2 synthesis inhibitor furegrelate, the PGI2 synthesis inhibitor tranylcypromine (TCP), or the thromboxane-prostanoid (TP) receptor antagonist SQ-29 548. Furthermore, TXA2, PGI2, PGF(2 alpha), and PGE2 release as well as the vasomotor effect of exogenous TXA2, PGI2, PGF(2 alpha), and PGE2 were measured. COX-2 expression was increased in aortas from orchidectomized rats. NS-398 did not modify the ACh-induced relaxation in arteries from both control or orchidectomized rats. Furegrelate did not modify the ACh-induced relaxation in aortas from control animals but, in aortas from orchidectomized rats, it increased that response. TCP decreased the ACh-induced relaxation in both groups. The TP receptor antagonist, SQ29 548 failed to modify ACh-induced relaxation in aortas from either rat group. Pre-incubating arteries from orchidectomized rats with TCP plus furegrelate did not modify the decrease in the ACh response induced by TCP alone, but this response was restored by co-incubation of TCP plus SQ29 548. ACh-induced TXA2, PGI2, PGF(2 alpha), and PGE2 release were increased by orchidectomy. The presence of furegrelate plus TCP increased the ACh-induced PGE2 release more in arteries from orchidectomized than in those from control rats. The contractile responses induced by the TXA2 mimetic U-46619 or by exogenous PGF(2 alpha) were similar in arteries from control and orchidectomized rats, while those induced by exogenous PGE2 were increased in arteries from orchidectomized rats; the vasodilator response induced by exogenous PGI2 was decreased in arteries from orchidectomized rats.These data show that endogenous male sex hormone deprivation increases COX-2 expression, the release of TXA2, PGI2, PGF(2 alpha), and PGE2 and the contractile response induced by exogenous PGE2 and TXA2, while it decreases the relaxation induced by exogenous PGI2. Despite the predominance of vasoconstrictor prostanoids derived from COX-2 in aortas from orchidectomized rats, the ACh-induced relaxation remains increased.
Naltrexone Does Not Relieve Uremic Pruritus
Authors: CHRISTIANE PAULI-MAGNUS, GERD MIKUS, DOMINIK M. ALSCHER, TILLMANN KIRSCHNER, WILFRIED NAGEL, NADJA GUGELER, TEUT RISLER, ELKE D. BERGER, ULRICH KUHLMANN, THOMAS METTANG
Journal: Journal of the American Society of Nephrology (2000)

Improvement of uremic pruritus was reported under short-term administration of the mu-receptor antagonists naltrexone and naloxone. The aim of the present study was to confirm the efficacy and safety of the oral mu-receptor antagonist naltrexone during a 4-wk treatment period in patients on hemodialysis and peritoneal dialysis. A placebo-controlled, double-blind crossover study of uremic patients with persistent, treatment-resistant pruritus was performed. Of 422 patients screened between December 1997 and June 1998, 93 suffered from pruritus and 23 were eligible for the study. Patients were started either with a 4-wk naltrexone sequence (50 mg/d) or matched placebo. This was followed by a 7-d washout, and patients continued with a 4-wk sequence of the alternate medication. Pruritus intensity was scored daily by a visual analogue scale (VAS) and weekly by a detailed score assessing scratching activity, distribution of pruritus, and frequency of pruritus-related sleep disturbance. Sixteen of 23 patients completed the study. During the naltrexone period, pruritus decreased by 29.2% (95% confidence interval [CI], 18.7 to 39.6) on the VAS and by 17.6% (95% CI, 4.2 to 31.1) on the detailed score. In comparison, pruritus decreased by 16.9% (95% CI, 6.8 to 26.9) on the VAS and by 22.3% (95% CI, 9.3 to 35.2) on the detailed score during the placebo period. The difference between the naltrexone and the placebo treatment period was not statistically significant. Nine of 23 patients complained of gastrointestinal disturbances during the naltrexone period compared with only one of 23 patients during the placebo period (P < 0.05). These results show that treatment of uremic pruritus with naltrexone is ineffective. In addition, a high incidence of adverse effects was observed during treatment with naltrexone.
Time Course of Tumor Metabolic Activity During Chemoradiotherapy of Esophageal Squamous Cell Carcinoma and Response to Treatment
Authors: Hinrich A. Wieder, Björn L.D.M. Brücher, Frank Zimmermann, Karen Becker, Florian Lordick, Ambros Beer, Markus Schwaiger, Ulrich Fink, Jörg Rüdiger Siewert, Hubert J. Stein, Wolfgang A. Weber
Journal: Journal of Clinical Oncology (2004)

To evaluate the time course of therapy-induced changes in tumor glucose use during chemoradiotherapy of esophageal squamous cell carcinoma (ESCC) and to correlate the reduction of metabolic activity with histopathologic tumor response and patient survival.Thirty-eight patients with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) scheduled to undergo a 4-week course of preoperative simultaneous chemoradiotherapy followed by esophagectomy were included. Patients underwent positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) before therapy (n = 38), after 2 weeks of initiation of therapy (n = 27), and preoperatively (3 to 4 weeks after chemoradiotherapy; n = 38). Tumor metabolic activity was quantitatively assessed by standardized uptake values (SUVs). Results Mean tumor FDG uptake before therapy was 9.3 +/- 2.8 SUV and decreased to 5.7 +/- 1.9 SUV 14 days after initiation of chemoradiotherapy (-38% +/- 18%; P <.0001). The preoperative scan showed an additional decrease of metabolic activity to 3.3 +/- 1.1 SUV (P <.0001). In histopathologic responders (< 10% viable cells in the resected specimen), the decrease in SUV from baseline to day 14 was 44% +/- 15%, whereas it was only 21% +/- 14% in nonresponders (P =.0055). Metabolic changes at this time point were also correlated with patient survival (P =.011). In the preoperative scan, tumor metabolic activity had decreased by 70% +/- 11% in histopathologic responders and 51% +/- 21% in histopathologic nonresponders.Changes in tumor metabolic activity after 14 days of preoperative chemoradiotherapy are significantly correlated with tumor response and patient survival. This suggests that FDG-PET might be used to identify nonresponders early during neoadjuvant chemoradiotherapy, allowing for early modifications of the treatment protocol.
Effect of a new synthetic ascorbic acid derivative as a free radical scavenger on the development of acute pancreatitis in mice.
Authors: A Nonaka, T Manabe, T Tobe
Journal: Gut (1991)

The therapeutic effects of CV 3611, a new synthetic free radical scavenger prepared from an ascorbic acid derivative, on choline deficient, ethionine enriched (CDE) diet induced acute pancreatitis in mice were evaluated and compared with those of superoxide dismutase. Time/course studies after subcutaneous injection of CV 3611 in normal mice showed a peak plasma concentration of mean (SEM) 0.54 (0.09) micrograms/ml at one hour, with a gradual decrease over the next 10 hours, while a peak concentration in pancreatic tissue of mean (SEM) 425 (33) ng/g tissue was achieved at three hours and the drug was undetectable at 12 hours. Survival rates and activities of pancreatic enzymes (amylase, lipase, elastase I) were compared in control mice and animals that received CV 3611 before or at the time of feeding the CDE diet. The survival rate was observed in a no treatment group and mice given pretreatment or treatment with CV 3611 or superoxide dismutase. The survival rate was significantly better in the treatment group given CV 3611 (p less than 0.02), but superoxide dismutase had no significant effect on survival. The increases in the three serum enzyme activities were significantly less at 48 hours in the groups given pretreatment or treatment with CV 3611 than in the no treatment group. These results indicate that CV 3611, which has been proved to pass through the cell membrane and to have a long half life in plasma and tissue, had an important therapeutic effect on the development of acute pancreatitis. They also suggest that oxygen derived free radicals may play an important role in the development of acute pancreatitis.
Effect of Insulin Glargine and n-3FA on Carotid Intima-Media Thickness in People With Dysglycemia at High Risk for Cardiovascular Events
Authors: Eva M. Lonn, Jackie Bosch, Rafael Diaz, Patricio Lopez-Jaramillo, Ambady Ramachandran, Nicolae Hâncu, Markolf Hanefeld, Henry Krum, Lars Ryden, Sandra Smith, Matthew J. McQueen, Leanne Dyal, Salim Yusuf, Hertzel C. Gerstein
Journal: Diabetes Care (2013)

To evaluate the effects of insulin glargine and n-3 polyunsaturated fatty acid (n-3FA) supplements on carotid intima-media thickness (CIMT).We enrolled 1,184 people with cardiovascular (CV) disease and/or CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes in a randomized multicenter 2 × 2 factorial design trial. Participants received open-label insulin glargine (targeting fasting glucose levels ≤ 5.3 mmol/L [95 mg/dL]) or standard glycemic care and double-blind therapy with a 1-g capsule of n-3FA or placebo. The primary trial outcome was the annualized rate of change in maximum CIMT for the common carotid, bifurcation, and internal carotid artery segments. Secondary outcomes were the annualized rates of change in maximum CIMT for the common carotid and the common carotid plus bifurcation, respectively. Baseline followed by annual ultrasounds were obtained during a median follow-up of 4.9 years.Compared with standard care, insulin glargine reduced the primary CIMT outcome, but the difference was not statistically significant (difference = 0.0030 ± 0.0021 mm/year; P = 0.145) and significantly reduced the secondary CIMT outcomes (differences of 0.0033 ± 0.0017 mm/year [P = 0.049] and 0.0045 ± 0.0021 mm/year [P = 0.032], respectively). There were no differences in the primary and secondary outcomes between the n-3FA supplement and placebo groups.In people with CV disease and/or CV risk factors and dysglycemia, insulin glargine used to target normoglycemia modestly reduced CIMT progression, whereas daily supplementation with n-3FA had no effect on CIMT progression.
Comparative Efficacy of Inactivated and Live Attenuated Influenza Vaccines
Authors: Arnold S. Monto, Suzanne E. Ohmit, Joshua G. Petrie, Emileigh Johnson, Rachel Truscon, Esther Teich, Judy Rotthoff, Matthew Boulton, John C. Victor
Journal: New England Journal of Medicine (2009)

The efficacy of influenza vaccines may vary from year to year, depending on a variety of factors, and may differ for inactivated and live attenuated vaccines.We carried out a randomized, double-blind, placebo-controlled trial of licensed inactivated and live attenuated influenza vaccines in healthy adults during the 2007-2008 influenza season and estimated the absolute and relative efficacies of the two vaccines.A total of 1952 subjects were enrolled and received study vaccines in the fall of 2007. Influenza activity occurred from January through April 2008, with the circulation of influenza types A (H3N2) (about 90%) and B (about 9%). Absolute efficacy against both types of influenza, as measured by isolating the virus in culture, identifying it on real-time polymerase-chain-reaction assay, or both, was 68% (95% confidence interval [CI], 46 to 81) for the inactivated vaccine and 36% (95% CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50% (95% CI, 20 to 69) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine. The absolute efficacy against the influenza A virus was 72% (95% CI, 49 to 84) for the inactivated vaccine and 29% (95% CI, -14 to 55) for the live attenuated vaccine, with a relative efficacy of 60% (95% CI, 33 to 77) for the inactivated vaccine.In the 2007-2008 season, the inactivated vaccine was efficacious in preventing laboratory-confirmed symptomatic influenza A (predominately H3N2) in healthy adults. The live attenuated vaccine also prevented influenza illnesses but was less efficacious. (ClinicalTrials.gov number, NCT00538512.)
Age-Related Risk Profile and Chemotherapy Dose Response in Acute Myeloid Leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group
Authors: Thomas Büchner, Wolfgang E. Berdel, Claudia Haferlach, Torsten Haferlach, Susanne Schnittger, Carsten Müller-Tidow, Jan Braess, Karsten Spiekermann, Joachim Kienast, Peter Staib, Andreas Grüneisen, Wolfgang Kern, Albrecht Reichle, Georg Maschmeyer, Carlo Aul, Eva Lengfelder, Maria-Cristina Sauerland, Achim Heinecke, Bernhard Wörmann, Wolfgang Hiddemann
Journal: Journal of Clinical Oncology (2008)

The purpose of the study was to assess the contribution of age and disease variables to the outcome of untreated patients with acute myeloid leukemia (AML) receiving varying intensive induction chemotherapy.Patients 16 to 85 years of age with primary AML, known karyotype, and uniform postremission chemotherapy enrolled onto two consecutive trials were eligible and were randomly assigned to induction either with a standard-dose (cytarabine, daunorubicin, and 6-thioguanine) and a high-dose (cytarabine and mitoxantrone) combination, or with two courses of the high-dose combination. Subgroups were defined by karyotype, nucleophosmin and FLT3 mutation, WBC count, serum lactate dehydrogenase, and residual blasts.In 1,284 patients, the overall survival at 4 years in those younger and older than 60 years was 37% versus 16% (P < .001) and the ongoing remission duration was 46% versus 22% (P < .001). Similar age-related differences in outcome were found for all defined subgroups. No difference in outcome according to randomly assigned treatment regimen was observed in any age group or prognostic subset. Regarding prognostic subgroups, molecular factors were also considered.Under harmonized conditions, older and younger patients with AML show modest differences in their risk profiles and equally no dose response to intensified chemotherapy. Their observed fundamental difference in outcome across all subgroups remains unexplained. Further molecular investigation may elucidate the age effect in AML and identify new targets.
Alterations in Glucose Metabolism in the Elderly Patient with Diabetes
Authors: Graydon S Meneilly, Keith Dawson, Daniel Tessier
Journal: Diabetes Care (1993)

Objective— To determine the alterations in glucose metabolism in elderly patients with NIDDM. Research Design and Methods— We studied 9 healthy elderly control subjects (73 ± 1 yr of age; body mass index 25.7 ± 0.4 kg/m2) and 9 untreated elderly NIDDM patients (72 ± 2 yr of age; BMI 25.9 ± 0.5 kg/m2). Each subject underwent a 3-h oral glucose tolerance test (40 g/m2); a 2-h hyperglycemic glucose clamp study (glucose 5.4 mM above basal); and a 4-h euglycemic insulin clamp (40 mM · m2 · min−1). Tritiated glucose methodology was used to measure glucose production and disposal rates during the euglycemic clamp. Results— Patients with NIDDM had a higher fasting glucose (9.3 ± 0.3 vs. 5.1 ± 0.1 mM in control subjects vs. NIDDM patients, respectively, P &amp;lt; 0.001) and a greater area under the curve for glucose during the OGTT (16.0 ± 0.6 vs. 6.7 ± 0.3 mM in control subjects vs. NIDDM patients, respectively, P &amp;lt; 0.01) than the healthy control subjects. During the hyperglycemic clamp, patients with NIDDM had an absent first-phase insulin response (112 ± 6 vs. 250 ± 31 pM in control subjects vs. NIDDM patients, respectively, P &amp;lt; 0.01), and a blunted second-phase insulin response (159 ± 11 vs. 337 ± 46 pM in control subjects vs. NIDDM patients, respectively, P &amp;lt; 0.01). Before the euglycemic clamp, fasting insulin (99 ± 5 vs. 111 ± 10 pM in control subjects vs. NIDDM patients, respectively) and hepatic glucose production (11.8 ± 0.7 vs. 11.5 ± 0.5 μmol · kg−1 μ min−1 in control subjects vs. NIDDM patients, respectively) were similar. Steady-state (180–240 min) glucose disposal rates during the euglycemic clamp were slightly, but not significantly, higher in the normal control subjects (36.5 ± 1.1 vs. 33.1 ± 1.9 μmol · kg−1 · min−1 in control subjects vs. NIDDM patients, respectively, NS). Conclusions— We conclude that NIDDM in nonobese elderly subjects is characterized by a marked impairment in insulin release. This may be attributable to the toxic effects of chronic hyperglycemia on the β-cell. When compared with age-matched control subjects, the NIDDM patients showed no increase in fasting insulin or hepatic glucose production, and insulin resistance was mild.
Severe pulmonary hypertension in patients with emphysema but preserved FEV1: Prognosis and response to treatment
Authors: Melanie Brewis, Alistair Church, Andrew Peacock, Martin Johnson
Journal: European Respiratory Journal (2013)

Mild to moderate pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease. A smaller proportion present with severe PH with mean pulmonary artery pressures (mPAP) of >35mmHg. The role of PH therapies in this group is unknown.   Methods :34 patients with CT evidence of emphysema but preserved FEV1(standardised residuals >-1.645) and mPAP >35mmHg at right heart catheterisation were diagnosed between 2000-2012. 54 idiopathic PAH (IPAH) patients from the same period were used for comparison. Six minute walk distance (6MWD), NTproBNP and functional class (Fc) were assessed at baseline and following 3 months of PH therapy.   Results :In comparison to IPAH patients, there was no significant improvement in outcomes. (table1.) 1 and 3 year survival were worse in the emphysema group (Fig1). The strongest predictor of survival in the emphysema group was right atrial pressure (P   Conclusion . Compared with IPAH patients, patients with emphysema, preserved FEV1 and severe PH have worse survival and appear to respond poorly to PH targeted therapy.
Histopathology of intestinal inflammation related to reactive arthritis.
Authors: C Cuvelier, C Barbatis, H Mielants, M De Vos, H Roels, E Veys
Journal: Gut (1987)

This study has identified a group of patients with inflammatory chronic, or relapsing acute arthritis who even in the absence of gastrointestinal symptoms have histological evidence of ileocolitis. At colonoscopy simultaneous biopsies of the terminal ileum and colon were taken from 108 patients with reactive arthritis (n = 55) or ankylosing spondylitis (n = 53), 47 patients with other rheumatic diseases and 19 control patients suffering from colonic polyps, adenocarcinoma, or chronic constipation. All control patients and all but one patient with rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, lumbar back ache, and psoriatic arthritis did not have histological evidence of acute or chronic inflammatory bowel disease. In contrast, in 30 of 35 (56.6%) patients with ankylosing spondylitis, and in 37 of 55 (67%) patients with reactive arthritis, regardless of HLA B27 phenotype, there was histological evidence of inflammatory bowel disease with features either of acute enterocolitis, or early Crohn's disease. Only 18 of 67 (27%) of the patients with histological gut inflammation, however, had intestinal symptoms.