tbuckley/cabot-search huggingface dataset:
Effect of Renal Sympathetic Denervation on Glucose Metabolism in Patients With Resistant Hypertension
Authors: Felix Mahfoud, Markus Schlaich, Ingrid Kindermann, Christian Ukena, Bodo Cremers, Mathias C. Brandt, Uta C. Hoppe, Oliver Vonend, Lars C. Rump, Paul A. Sobotka, Henry Krum, Murray Esler, Michael Böhm
Journal: Circulation (2011)

Background— Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension. Methods and Results— We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A 1c , calculated insulin sensitivity (homeostasis model assessment–insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96±3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by −28/−10 mm Hg ( P &lt;0.001) and −32/−12 mm Hg ( P &lt;0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118±3.4 to 108±3.8 mg/dL ( P =0.039). Insulin levels were decreased from 20.8±3.0 to 9.3±2.5 μIU/mL ( P =0.006) and C-peptide levels from 5.3±0.6 to 3.0±0.9 ng/mL ( P =0.002). After 3 months, homeostasis model assessment–insulin resistance decreased from 6.0±0.9 to 2.4±0.8 ( P =0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL ( P =0.012). There were no significant changes in blood pressure or metabolic markers in the control group. Conclusions— Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk. Clinical Trial Registration— URL: http://www.ClinicalTrials.gov . Unique identifiers: NCT00664638 and NCT00888433.
Recovery of body composition improves long-term outcomes after lung volume reduction surgery for emphysema
Authors: D. Mineo, V. Ambrogi, V. Lauriola, E. Pompeo, T.C. Mineo
Journal: European Respiratory Journal (2010)

Nutritional status deteriorates along with progression of emphysema, with the decline of body composition correlating with risk of disease-related events. Lung volume reduction surgery (LVRS), by improving respiratory function and recovering body composition, may influence long-term disease-related morbidity and mortality when compared to respiratory rehabilitation (RR). In this non-randomised study, 44 male patients with moderate-to-severe emphysema underwent LVRS, while 35 received RR. Respiratory parameters, body composition, number and time-to-occurrence of disease-related events were evaluated for 5 yrs. After LVRS, respiratory and nutritional parameters had significantly greater and longer lasting improvements than after RR. Disease-related events occurred later and less frequently after surgery than after rehabilitation, with better morbidity and mortality survival curves (p<0.01 and p<0.03, respectively). Body mass index (BMI) > or =23kg x m(-2), BODE (BMI, airflow obstruction, dyspnoea, exercise capacity) index < or =2 and fat-free mass index (FFMI) > or =16kg x m(-2) at 1 yr were the best positive predictors of post-operative outcomes (p<0.03, p<0.04 and p<0.005, respectively). Reduction in residual volume at 36 months after surgery was significantly correlated with the increase of BMI (rho = -0.56, p = 0.009) and FFMI (rho = -0.64, p = 0.001). LVRS significantly and durably improved respiratory function and body composition over RR. Relationships among residual volume, BMI, FFMI and disease-related events suggest that recovery in respiratory dynamics improves nutritional status, thus significantly reducing long-term disease-related morbidity and mortality.
The Types of Retinal Ganglion Cells: Current Status and Implications for Neuronal Classification
Authors: Joshua R. Sanes, Richard H. Masland
Journal: Annual Review of Neuroscience (2015)

In the retina, photoreceptors pass visual information to interneurons, which process it and pass it to retinal ganglion cells (RGCs). Axons of RGCs then travel through the optic nerve, telling the rest of the brain all it will ever know about the visual world. Research over the past several decades has made clear that most RGCs are not merely light detectors, but rather feature detectors, which send a diverse set of parallel, highly processed images of the world on to higher centers. Here, we review progress in classification of RGCs by physiological, morphological, and molecular criteria, making a particular effort to distinguish those cell types that are definitive from those for which information is partial. We focus on the mouse, in which molecular and genetic methods are most advanced. We argue that there are around 30 RGC types and that we can now account for well over half of all RGCs. We also use RGCs to examine the general problem of neuronal classification, arguing that insights and methods from the retina can guide the classification enterprise in other brain regions.
Non-surgical treatment for afferent loop syndrome in recurrent gastric cancer complicated by peritoneal carcinomatosis: percutaneous transhepatic duodenal drainage followed by24-hour infusion of high-dose fluorouracil and leucovorin
Authors: K.-D. Lee, T.-W. Liu, C.-W. Wu, C.-M. Tiu, J.M. Liu, T.-R. Chung, J.-Y. Chang, J. Whang-Peng, L.-T. Chen
Journal: Annals of Oncology (2002)
A double blind, multicentre, placebo controlled trial of lornoxicam in patients with osteoarthritis of the hip and knee.
Authors: H Berry, H A Bird, C Black, D R Blake, A M Freeman, D N Golding, E B Hamilton, M I Jayson, B Kidd, H Kohn
Journal: Annals of the Rheumatic Diseases (1992)

Lornoxicam is a new non-steroidal anti-inflammatory agent (NSAID) with a similar pharmacological profile to other oxicams and a potency 10 times greater than piroxicam. A multicentre, randomised, double blind, parallel group study was undertaken to compare the efficacy and tolerance of four weeks9 treatment with lornoxicam (6 mg once daily, 4 mg twice daily, and 6 mg twice daily) and placebo in patients with osteoarthritis of the hip or knee. A dose related efficacy of lornoxicam was shown by the numbers of patients in each treatment group who withdrew from the trial owing to inadequate symptom relief (12/40 (30%) receiving placebo, 6/40 (15) receiving lornoxicam 6 mg daily, 4/40 (10%) receiving lornoxicam 8 mg daily, and none receiving lornoxicam 12 mg daily). This effect was confirmed by pain relief scores, which were significantly better than placebo during treatment with lornoxicam 8 mg and 12 mg daily, the effect of 12 mg daily being significantly superior to that of 8 mg daily. Similar results were obtained from functional status scores. Mean functional index (Lequesne) scores were significantly greater than placebo only at a daily dose of 12 mg lornoxicam. Lornoxicam was generally well tolerated, though some gastrointestinal side effects were seen as has been reported with other NSAIDs. Laboratory investigations showed no evidence of drug toxicity.
The incidence of rheumatoid arthritis in the UK: comparisons using the 2010 ACR/EULAR classification criteria and the 1987 ACR classification criteria. Results from the Norfolk Arthritis Register
Authors: Jennifer H Humphreys, Suzanne M M Verstappen, Kimme L Hyrich, Jacqueline R Chipping, Tarnya Marshall, Deborah P M Symmons
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> The development of new classification criteria for rheumatoid arthritis (RA) calls for a re-estimation of RA incidence rates. The objectives of this study were to estimate the age and sex-specific incidence rates (IR) of RA in Norfolk, England using the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism criteria, and to compare those with IRs estimated using the 1987 ACR criteria. <h3>Setting</h3> The Norfolk Arthritis Register (NOAR), a large primary care inception cohort of patients with inflammatory oligo- and polyarthritis (IP) aged ≥ 16. <h3>Methods</h3> All patients notified to NOAR from 1990-5 with symptom onset in 1990 were included. The former Norwich Health Authority population was the denominator. Age and sex specific IRs using 1987 and 2010 classification criteria were calculated at baseline visit, annually for the first 3 years and at 5 years. <h3>Results</h3> 260 patients were notified to NOAR with symptom onset in 1990 and without an alternative diagnosis. IRs applying the 2010 criteria at baseline were 54/100 000 for women and 25/100 000 for men. Age and sex-specific IRs using the 2010 classification criteria at baseline were similar to cumulative IRs applying the 1987 criteria up to 5 years. However, some patients only ever satisfied one set of criteria and a proportion of IA patients (20%) did not satisfy either criteria set over 5 years. <h3>Conclusions</h3> The 2010 criteria classify similar numbers of patients as having RA at baseline, as the 1987 criteria would have taken up to 5 years to identify.
Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies
Authors: Michal J. Besser, Ronnie Shapira-Frommer, Orit Itzhaki, Avraham J. Treves, Douglas B. Zippel, Daphna Levy, Adva Kubi, Noa Shoshani, Dragoslav Zikich, Yaara Ohayon, Daniel Ohayon, Bruria Shalmon, Gal Markel, Ronit Yerushalmi, Sara Apter, Alon Ben-Nun, Eytan Ben-Ami, Avichai Shimoni, Arnon Nagler, Jacob Schachter
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Adoptive cell transfer (ACT) using autologous tumor-infiltrating lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic patients with melanoma. Here, we present the intent-to-treat analysis of TIL ACT and analyze parameters predictive to response as well as the impact of other immunotherapies. Experimental Design: Eighty patients with stage IV melanoma were enrolled, of which 57 were treated with unselected/young TIL and high-dose interleukin-2 (IL-2) following nonmyeloablative lymphodepleting conditioning. Results: TIL cultures were established from 72 of 80 enrolled patients. Altogether 23 patients were withdrawn from the study mainly due to clinical deterioration during TIL preparation. The overall response rate and median survival was 29% and 9.8 months for enrolled patients and 40% and 15.2 months for treated patients. Five patients achieved complete and 18 partial remission. All complete responders are on unmaintained remission after a median follow-up of 28 months and the 3-year survival of responding patients was 78%. Multivariate analysis revealed blood lactate-dehydrogenase levels, gender, days of TIL in culture, and the total number of infused CD8+ cells as independent predictive markers for clinical outcome. Thirty-two patients received the CTLA-4-blocking antibody ipilimumab prior or post TIL infusion. Retrospective analysis revealed that nonresponders to ipilimumab or IL-2 based therapy had the same overall response rate to ACT as other patients receiving TIL. No additional toxicities to TIL therapy occurred following ipilimumab treatment. Conclusion: Adoptive transfer of TIL can yield durable and complete responses in patients with refractory melanoma, even when other immunotherapies have failed. Clin Cancer Res; 19(17); 4792–800. ©2013 AACR.
Oncology Physician and Nurse Practices and Attitudes Regarding Offering Clinical Trial Results To Study Participants
Authors: Ann H Partridge, Nadia Hackett, Emily Blood, Rebecca Gelman, Steven Joffe, Susan Bauer-Wu, Katherine Knudsen, Karen Emmons, Deborah Collyar, Richard L Schilsky, Eric P Winer
Journal: JNCI Journal of the National Cancer Institute (2004)

Despite recent interest on the part of advocates and researchers of oncology clinical trials in sharing study results, participants in these trials are not routinely informed about the results. We identified oncology physicians and nurses through the Cancer and Leukemia Group B database and surveyed them about sharing clinical trial results with participants. Of 1977 eligible members, 796 (40.3%) responded to the mailed survey, 497 (62.4%) of whom reported that they offer trial results to participants less than one-fifth of the time. A total of 576 (72.4%) of responders believed that most patients want to know the results of studies, and 634 (79.7%) of responders expressed willingness to offer results to most study participants in the future, believing that most patients want to know trial results and that routinely offering results would not have a negative effect on patients. Concerns of some responders about routinely offering trial results included negative emotional effect on patients, patient difficulty understanding the information, and resources required to offer the results. Of concern, 16.2% (129/796) of responders believed an obligation to offer results to study participants would make them less likely to enroll patients on studies. Future studies should consider sharing trial results with patients and evaluating the process and its effect on both patients and clinicians.
Dynamic magnetic resonance imaging assessment of vascular targeting agent effects in rat intracerebral tumor models
Authors: L. L. Muldoon, S. Gahramanov, X. Li, D. J. Marshall, D. F. Kraemer, E. A. Neuwelt
Journal: Neuro-Oncology (2010)

We used dynamic MRI to evaluate the effects of monoclonal antibodies targeting brain tumor vasculature. Female athymic rats with intracerebral human tumor xenografts were untreated or treated with intetumumab, targeting αV-integrins, or bevacizumab, targeting vascular endothelial growth factor (n = 4–6 per group). Prior to treatment and at 1, 3, and 7 days after treatment, we performed standard MRI to assess tumor volume, dynamic susceptibility-contrast MRI with the blood-pool iron oxide nanoparticle ferumoxytol to evaluate relative cerebral blood volume (rCBV), and dynamic contrast-enhanced MRI to assess tumor vascular permeability. Tumor rCBV increased by 27 ± 13% over 7 days in untreated rats; intetumumab increased tumor rCBV by 65 ± 10%, whereas bevacizumab reduced tumor rCBV by 31 ± 10% at 7 days (P < .001 for group and day). Similarly, intetumumab increased brain tumor vascular permeability compared with controls at 3 and 7 days after treatment, whereas bevacizumab decreased tumor permeability within 24 hours (P = .0004 for group, P = .0081 for day). All tumors grew over the 7-day assessment period, but bevacizumab slowed the increase in tumor volume on MRI. We conclude that the vascular targeting agents intetumumab and bevacizumab had diametrically opposite effects on dynamic MRI of tumor vasculature in rat brain tumor models. Targeting αV-integrins increased tumor vascular permeability and blood volume, whereas bevacizumab decreased both measures. These findings have implications for chemotherapy delivery and antitumor efficacy.
Liver Angiotensinogen Is the Primary Source of Renal Angiotensin II
Authors: Taiji Matsusaka, Fumio Niimura, Akihiro Shimizu, Ira Pastan, Akihiko Saito, Hiroyuki Kobori, Akira Nishiyama, Iekuni Ichikawa
Journal: Journal of the American Society of Nephrology (2012)

Angiotensin II content in the kidney is much higher than in the plasma, and it increases more in kidney diseases through an uncertain mechanism. Because the kidney abundantly expresses angiotensinogen mRNA, transcriptional dysregulation of angiotensinogen within the kidney is one potential cause of increased renal angiotensin II in the setting of disease. Here, we observed that kidney-specific angiotensinogen knockout mice had levels of renal angiotensinogen protein and angiotensin II that were similar to those levels of control mice. In contrast, liver-specific knockout of angiotensinogen nearly abolished plasma and renal angiotensinogen protein and renal tissue angiotensin II. Immunohistochemical analysis in mosaic proximal tubules of megalin knockout mice revealed that angiotensinogen protein was incorporated selectively in megalin-intact cells of the proximal tubule, indicating that the proximal tubule reabsorbs filtered angiotensinogen through megalin. Disruption of the filtration barrier in a transgenic mouse model of podocyte-selective injury increased renal angiotensin II content and markedly increased both tubular and urinary angiotensinogen protein without an increase in renal renin activity, supporting the dependency of renal angiotensin II generation on filtered angiotensinogen. Taken together, these data suggest that liver-derived angiotensinogen is the primary source of renal angiotensinogen protein and angiotensin II. Furthermore, an abnormal increase in the permeability of the glomerular capillary wall to angiotensinogen, which characterizes proteinuric kidney diseases, enhances the synthesis of renal angiotensin II.
Right ventricular involvement in anterior myocardial infarction: a translational approach
Authors: Vicente Bodi, Juan Sanchis, Luis Mainar, Francisco J. Chorro, Julio Nunez, Jose V. Monmeneu, Fabian Chaustre, Maria J. Forteza, Amparo Ruiz-Sauri, Maria P. Lopez-Lereu, Cristina Gomez, Inmaculada Noguera, Ana Diaz, Francisco Giner, Angel Llacer
Journal: Cardiovascular Research (2010)

The aim of the present study was to evaluate the involvement of the right ventricle (RV) in reperfused anterior ST-elevation myocardial infarction (STEMI). Left anterior descending (LAD)-perfused area (using thioflavin-S staining after selective infusion in proximal LAD artery, %), infarct size (using triphenyltetrazolium chloride staining, %), and salvaged myocardium (% of LAD-perfused area) in the right and left ventricle (LV) were quantified in a 90-min LAD occlusion 3-day reperfusion model in swine (n = 8). Additionally, we studied, using cardiovascular magnetic resonance, 20 patients with a first STEMI due to proximal LAD occlusion treated with primary angioplasty. Area at risk (T2-weighted sequence, %), infarct size (late enhancement imaging, %), and salvaged myocardium (% of area at risk) in the right and LV were quantified. In swine, a large LAD-perfused area was detected both in the right and LV (30 ± 5 vs. 62 ± 15%, P< 0.001) but more salvaged myocardium (94 ± 6 vs. 73 ± 11%, P< 0.001) resulted in a smaller right ventricular infarct size (2 ± 1 vs. 16 ± 5%, P< 0.001). Similarly, in patients a large area at risk was detected both in the right and LV (34 ± 13 vs. 43 ± 12%, P = 0.02). More salvaged myocardium (94 ± 10 vs. 33 ± 26%, P < 0.001) resulted in a smaller infarct size (2 ± 3 vs. 30 ± 16%, P< 0.001) in the RV. In reperfused extensive anterior STEMI, a large area of the RV is at risk but the resultant infarct size is small.
Acute reversal of allergen-induced airway hyperresponsiveness (AHR) by olodaterol is synergistically enhanced by tiotropium bromide
Authors: M. Smit, A.B. Zuidhof, I.S.T. Bos, H. Maarsingh, R. Gosens, J. Zaagsma, H. Meurs
Journal: European Respiratory Journal (2011)

Bronchodilators, like β2-agonists and anticholinergics, are a mainstay therapy for asthma and COPD. Recently, the ultra-long acting β2-agonist olodaterol has been found effective for over 24h in asthma and COPD patients. Increased cholinergic tone, common to these patients, may decrease β2-agonist responsiveness. Using a guinea pig model of allergic asthma, we investigated the reversal of allergen-induced AHR by olodaterol, alone and in combination with the long acting anticholinergic tiotropium bromide. Airway responsiveness was assessed as histamine PC100 (provocative concentration increasing pleural pressure by 100%) at baseline (24 h before challenge) and after the early asthmatic reaction (EAR; 5 h after challenge). Phosphate buffered saline (PBS), 1 mM olodaterol and/or 0.1 mM tiotropium (nebulizer concentrations, 3 min) were inhaled at 5.5 h after challenge, followed by PC100 determinations at 6.5 h and at 24 h (after the late asthmatic reaction; LAR). Allergen challenge induced AHR to histamine after the EAR (8.3-fold decrease in PC100), which was unaffected by PBS. By contrast, olodaterol strongly reversed the AHR after the EAR (11.4-fold increase in PC100). Tiotropium, which slightly reversed the AHR by itself (2.4-fold), synergistically enhanced the effect of olodaterol to 21.0-fold. After the LAR, the PBS-treated animals were still hyperresponsive (2.3-fold decreased PC100). Tiotropium did not affect this AHR, whereas olodaterol, with or without tiotropium, was still protective. In conclusion, endogenous acetylcholine importantly reduces the reversibility of allergen-induced AHR by β2-agonists.

Supported by Boehringer Ingelheim Pharma.
“A La Carte” treatment of portal hypertension: Adapting medical therapy to hemodynamic response for the prevention of bleeding
Authors: C Bureau
Journal: Hepatology (2002)

We report the results of adapting medical therapy to the monitoring of hemodynamic response in the prevention of a first variceal bleeding or rebleeding in patients with cirrhosis. Hepatic venous pressure gradient (HVPG) was measured before and after propranolol was initiated. The patients were considered responders if HVPG decreased below 12 mm Hg or at least 20% as compared with baseline value. If patients were not responders, isosorbide-5 mononitrate (I-5MN) was added, and a third hemodynamic study was performed. Thereafter, the patients were followed for a mean of 28 months. Thirty-four consecutive patients were treated to prevent a first bleeding episode in 20 patients and a rebleeding in 14 patients. HVPG value was initially 19.8 +/- 4.6 mm Hg and decreased to 17.6 +/- 5.7 mm Hg (P <.05) after propranolol alone. Thirteen patients (38%) were responders to propranolol. I-5MN improved hemodynamic response in 7 cases. Among these 20 (59%) hemodynamic responders, only 2 (10%) experienced variceal bleeding, as compared with 9 of 14 (64%) nonresponders (P <.05). Using multivariate analysis, only hemodynamic response was found to have an independent predictive value for the risk of variceal bleeding. In conclusion, hemodynamic response to drug therapy identifies patients who are efficiently protected from variceal bleeding as well as nonresponders in whom an alternative treatment should be considered.