tbuckley/cabot-search huggingface dataset:
New developments in drug delivery systems
Authors: Yie W. Chien
Journal: Medicinal Research Reviews (1990)

The rate-controlled drug delivery systems outlined above have been steadily introduced into the biomedical community since the middle of the 1970s. It is the author's belief that many more of the conventional drug delivery systems which we have been using for many decades will be gradually replaced, in coming years, by these high-tech-based rate-controlled drug delivery systems.
Left Ventricular Reverse Remodeling but Not Clinical Improvement Predicts Long-Term Survival After Cardiac Resynchronization Therapy
Authors: Cheuk-Man Yu, Gabe B. Bleeker, Jeffrey Wing-Hong Fung, Martin J. Schalij, Qing Zhang, Ernst E. van der Wall, Yat-Sun Chan, Shun-Ling Kong, Jeroen J. Bax
Journal: Circulation (2005)

In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study.Patients (n=141) with advanced heart failure (mean+/-SD age, 64+/-11 years; 73% men) who received CRT were followed up for a mean (+/-SD) of 695+/-491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of > or =9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank chi2=13.26, P=0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank chi2=17.1, P<0.0001), and heart failure events (11.5% versus 33.3%, log-rank chi2=8.71, P=0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause (beta=1.048, 95% confidence interval=1.019 to 1.078, P=0.001) and cardiovascular (beta=1.072, 95% confidence interval=1.033 to 1.112, P<0.001) mortality. Clinical parameters were unable to predict any outcome event.A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes.
Super paramagnetic iron oxide MRI shows defective Kupffer cell uptake function in non-alcoholic fatty liver disease
Authors: Taketoshi Asanuma, Masafumi Ono, Kei Kubota, Akira Hirose, Yoshihiro Hayashi, Toshiji Saibara, Osamu Inanami, Yasuhiro Ogawa, Hideaki Enzan, Saburo Onishi, Mikinori Kuwabara, Jude A Oben
Journal: Gut (2009)

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KCs), phagocytic liver-resident macrophages, provide a protective barrier against egress of endotoxin from the portal to the systemic circulation. It is not known if KC phagocytic function is impaired in NAFLD. Super-paramagnetic iron oxide (SPIO) magnetic resonance imaging is a comparative technology dependent on KC phagocytic function.To evaluate KC uptake function, in patients and experimental animals with NAFLD, using SPIO.Abdominal CT and histological examination of liver biopsy specimens were used to estimate the degree of steatosis in patients with NAFLD and controls with chronic hepatitis C. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline-deficient diet to induce non-alcoholic steatohepatitis (NASH), the more severe stage of NAFLD, and obese, insulin resistant, Zucker fa/fa rats with steatohepatitis, were also studied with SPIO-MRI and analysed for hepatic uptake of fluorescent microbeads. Immunohistochemical analysis evaluated the numbers of KCs in patients and rat livers.Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD than in controls and with the degree of steatosis on CT. RSE also positively correlated with the degree of steatosis on histology and was similarly higher in rats with induced severe NAFLD (NASH). On immunohistochemistry, defective phagocytic function was the result of reduced phagocytic uptake and not due to reduced KC numbers in rats or patients with NAFLD.KC uptake function is significantly impaired in patients with NAFLD and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.
Effect of Potassium Canrenoate, an Anti-aldosterone Agent, on Incidence of Ascites and Variceal Progression in Cirrhosis
Authors: Luigi Bolondi, Fabio Piscaglia, Angelo Gatta, Francesco Salerno, Mauro Bernardi, Antonio Ascione, Oscar Ferraù, David Sacerdoti, Stefania Visentin, Franco Trevisani, Roberto Mazzanti, Gabriele Donati, Umberto Arena, Paolo Gentilini
Journal: Clinical Gastroenterology and Hepatology (2006)
Infections of the Urinary Tract
Authors: Edward N. Cook
Journal: JAMA (1966)

During recent years, the doctrines propounded by many physicians, even in the field of internal medicine, have brought about an explosion of major significance concerning cause, diagnosis, and management of infections of the urinary tract. These physicians have outlined a number of tedious programs and complicated laboratory procedures which are most impractical for the average physician and for the urologist as well. Actually, these theoretical suggestions have offered little that is new or of value. For decades, most urologists have been aware of the importance of asepsis in obtaining specimens of urine for study and evaluation. The so-called explosion of the past decade concerning the use of the catheter is of value in that it has awakened the medical profession generally to these facts concerning the need for the strictest care in collecting and studying urinary sediment. Even if we grant that this contribution was worthwhile, it, unfortunately, was not
Modest changes in high-density lipoprotein concentration and metabolism with prolonged exercise training.
Authors: P D Thompson, E M Cullinane, S P Sady, M M Flynn, D N Bernier, M A Kantor, A L Saritelli, P N Herbert
Journal: Circulation (1988)

High-density lipoprotein (HDL) metabolism was studied in eight sedentary men before and after 14 and 32-48 weeks of exercise training. Subjects rode stationary bicycles 1 hour daily, 5 days each week for 14 weeks (n = 8), and 4 days each week thereafter for a total of 32-48 weeks (n = 7) of training. HDL metabolism was assessed with 125I-radiolabeled autologous HDL while subjects consumed defined diets. Maximal oxygen uptake increased 26 +/- 7% (p less than 0.001) after 14 weeks but did not increase further with more prolonged training. Body weight and estimated body fat did not change. HDL cholesterol increased 5 +/- 3 mg/dl, and triglycerides decreased 19 +/- 23 mg/dl after 14 weeks (p less than 0.025 for both), but there were no additional changes with continued training. Postheparin plasma lipoprotein lipase activity was 22% higher than baseline activity after both 14 (p less than 0.025) and 32 or more weeks of exercise. In contrast, hepatic triglyceride lipase activity was 16 +/- 8% and 15 +/- 8% lower than baseline at each measurement (p less than 0.005 for both). The disappearance rate of triglycerides after an intravenously administered fat solution was 24 +/- 24% higher at 14 weeks and 49 +/- 18% (p less than 0.005) higher after more prolonged training. Total and low-density lipoprotein cholesterol and apolipoprotein A-I and A-II concentrations at the end of study were not different from initial values. Plasma volume was 8% above initial values at both post-training measurements. The biological half-life of apolipoprotein A-I was unchanged at 14 weeks but was 10 +/- 13% longer (p = 0.07) and increased in all but one subject at the end of the study. Half-life for apolipoprotein A-II was 8 +/- 8% (p = 0.031) and 11 +/- 14% (p = 0.06) above baseline at 14 and 32 or more weeks, respectively. The synthetic rates for apolipoproteins A-I and A-II were not different from baseline values at 32-48 weeks. We conclude that 8-11 months of exercise training in previously sedentary men enhances fat tolerance and increases HDL cholesterol concentrations by prolonging HDL survival. The changes in HDL apolipoprotein survival, however, do not approximate the differences previously noted between elite endurance athletes and sedentary men. Changes in HDL cholesterol concentration were not large and suggest that the potential for exercise-related changes in HDL may be modest in many subjects.
Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator
Authors: Christian J Hunter, André Dejam, Arlin B Blood, Howard Shields, Daniel B Kim-Shapiro, Roberto F Machado, Selamawit Tarekegn, Neda Mulla, Andrew O Hopper, Alan N Schechter, Gordon G Power, Mark T Gladwin
Journal: Nature Medicine (2004)
Caffeine versus methylphenidate and d-amphetamine in minimal brain dysfunction: a double-blind comparison
Authors: R D Huestis, L E Arnold, D J Smeltzer
Journal: American Journal of Psychiatry (1975)

The authors compared the efficacy of caffeine, methylphenidate, and d-amphetamine in children with minimal brain dysfunction using a double-blind crossover design. The slight improvement with caffeine was not significantly better than placebo. Both prescription drugs resulted in significant improvement and were significantly superior to caffeine. The authors suggest that the discrepancy between these results and an earlier, more optimistic report mat stem from the use in this study of pure caffeine rather than whole coffee.
Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function
Authors: Andrea Boni, Alexandria P. Cogdill, Ping Dang, Durga Udayakumar, Ching-Ni Jenny Njauw, Callum M. Sloss, Cristina R. Ferrone, Keith T. Flaherty, Donald P. Lawrence, David E. Fisher, Hensin Tsao, Jennifer A. Wargo
Journal: Cancer Research (2010)

Abstract Targeted therapy against the BRAF/mitogen-activated protein kinase (MAPK) pathway is a promising new therapeutic approach for the treatment of melanoma. Treatment with selective BRAF inhibitors results in a high initial response rate but limited duration of response. To counter this, investigators propose combining this therapy with other targeted agents, addressing the issue of redundancy and signaling through different oncogenic pathways. An alternative approach is combining BRAF/MAPK-targeted agents with immunotherapy. Preliminary evidence suggests that oncogenic BRAF (BRAFV600E) contributes to immune escape and that blocking its activity via MAPK pathway inhibition leads to increased expression of melanocyte differentiation antigens (MDA). Recognition of MDAs is a critical component of the immunologic response to melanoma, and several forms of immunotherapy capitalize on this recognition. Among the various approaches to inhibiting BRAF/MAPK, broad MAPK pathway inhibition may have deleterious effects on T lymphocyte function. Here, we corroborate the role of oncogenic BRAF in immune evasion by melanoma cells through suppression of MDAs. We show that inhibition of the MAPK pathway with MAPK/extracellular signal-regulated kinase kinase (MEK) inhibitors or a specific inhibitor of BRAFV600E in melanoma cell lines and tumor digests results in increased levels of MDAs, which is associated with improved recognition by antigen-specific T lymphocytes. However, treatment with MEK inhibitors impairs T lymphocyte function, whereas T-cell function is preserved after treatment with a specific inhibitor of BRAFV600E. These findings suggest that immune evasion of melanomas mediated by oncogenic BRAF may be reversed by targeted BRAF inhibition without compromising T-cell function. These findings have important implications for combined kinase-targeted therapy plus immunotherapy for melanoma. Cancer Res; 70(13); 5213–9. ©2010 AACR.
Solitary Brain Metastasis As First Manifestation of Small-Cell Parotid Gland Carcinoma With High Sensitivity to Temozolomide Therapy on Basis of Tumor O<sup>6</sup>-Methylguanine-DNA-Methyltransferase Expression
Authors: Ivan Lolli, Isabella Morra, Antonella Cimmino, Elisa Trevisan, Roberta Rudà, Michele Piombino, Giovanna Campanella, Anna Gillio Tos, Laura De Marco, Morena Trevisan, Valentina Fiano, Riccardo Soffietti
Journal: Journal of Clinical Oncology (2013)
What are we talking about here?
Authors: John Heil
Journal: Behavioral and Brain Sciences (2001)

Shepard provides an account of mechanisms underlying perceptual judgment or representation. Ought we to interpret the account as revealing principles on which those mechanisms operate or merely an account of principles to which their operation apparently conforms? The difference, invisible so long as we remain at a high level of abstraction, becomes important when we begin to consider implementation. [Shepard]
Oxidative degradation of leukotriene C4 by human monocytes and monocyte-derived macrophages.
Authors: M A Neill, W R Henderson, S J Klebanoff
Journal: The Journal of Experimental Medicine (1985)

Freshly isolated 2-h adherent normal human monocytes, when stimulated, degrade added leukotriene C4 (LTC4) by a myeloperoxidase (MPO) and H2O2-dependent mechanism. Among the stimuli effective in this regard are phorbol myristate acetate (PMA), the calcium ionophore A23187, opsonized zymosan, and N-formyl-methionine-leucine-phenylalanine (FMLP) when combined with cytochalasin B. The predominant products formed are the all-trans isomers of LTB4, 5-(S), 12-(R)-6-trans-LTB4 and 5-(S),12-(S)-6-trans-LTB4. Degradation is inhibited by azide and catalase, but not by superoxide dismutase. LTC4 degradation does not occur when MPO-deficient monocytes are used, unless MPO is added. Stimulated monocytes from patients with chronic granulomatous disease also are unable to degrade LTC4 under these conditions. Normal monocytes maintained in culture lose their ability to degrade LTC4. The addition of MPO to monocyte-derived macrophages increases degradation, particularly when the monolayers are pretreated with gamma-interferon. The oxidative degradation of LTC4 is a capacity shared by neutrophils, eosinophils, and mononuclear phagocytes, and may be an important mechanism for the modulation of leukotriene activity in inflammatory lesions.
Neuropeptide control of rat gastric mucosal blood flow. Increase by calcitonin gene-related peptide and vasoactive intestinal polypeptide, but not substance P and neurokinin A.
Authors: P Holzer, P H Guth
Journal: Circulation Research (1991)

Submucosal blood vessels of the mammalian stomach are densely innervated by neurons containing calcitonin gene-related peptide (CGRP), substance P, neurokinin A, and vasoactive intestinal polypeptide (VIP). Because all these peptides are vasodilators in certain vascular beds, we tested the hypothesis that rat alpha-CGRP, rat VIP, substance P, and neurokinin A are candidate mediators of noncholinergic vasodilator neurons in the gastric mucosa and submucosa. The experiments were performed on urethane-anesthetized Sprague-Dawley rats. Gastric mucosal blood flow (GMBF) was measured by the hydrogen gas clearance technique, and the peptides were infused close arterially to the stomach via a catheter inserted retrogradely in the splenic artery. Basal GMBF was in the range of 35-50 ml/min/100 g. Infusion of rat alpha-CGRP (15 and 75 pmol/min) significantly increased GMBF in a dose-dependent manner, whereas mean arterial blood pressure was significantly lowered only by the higher dose of CGRP. Substance P (125 and 625 pmol/min) and neurokinin A (50 and 250 pmol/min) failed to alter GMBF, although the higher dose of each peptide led to a significant decrease in mean arterial blood pressure. Infusion of rat VIP (25 pmol/min) failed to affect GMBF and mean arterial blood pressure, whereas a fivefold higher dose of VIP (125 pmol/min) led to a significant rise of GMBF and to significant hypotension. These findings indicate that substance P and neurokinin A are unlikely to be of physiological significance for the regulation of GMBF. CGRP and VIP, however, can be considered as candidate mediators of submucosal nerve endings involved in the neural control of GMBF.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of puncture and aspiration in expectant management of simple ovarian cysts: a randomised study
Authors: G. Zanetta, A. Lissoni, V. Torri, C. D. Valle, D. Trio, G. Rangoni, C. Mangioni
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objectives</b>: To assess the potential of expectant management for simple ovarian cysts diagnosed by transabdominal or transvaginal ultrasonography. To compare the results of needle aspiration with those achieved with simple observation. <b>Design</b>: Randomised trial. <b>Setting</b>: Hospital department of obstetrics and gynaecology. <b>Subjects</b>: 278 women with simple cysts randomly allocated to simple observation (143) or ultrasound guided fine needle aspiration (135) between 1990 and 1994. <b>Main outcome measures</b>: Resolution of cyst or development of malignancy. <b>Results</b>: After six months 269 were available for follow up. The rate of resolution was 46% (59/128) with aspiration and 44.6% (63/141) with observation. Only the diameter of the cyst (P&lt;0.0001) was a significant independent prognostic factor for resolution in a multivariate analysis. Age and treatment had no significant effect. One woman was subsequently found to have borderline malignant changes on histopathological examination. Her cyst was detected by transabdominal ultrasonography. <b>Conclusions</b>: Expectant management for up to six months does not cause risks for the patients and allows spontaneous resolution in over a third of cases, avoiding the costs and risks of unnecessary surgery. Aspiration does not provide better results than simple observation <h3>Key messages</h3> Most of these masses are benign After follow up of six months the rate of resolu- tion was similar in those who had had their cysts aspirated and those who had had them observed Only the diameter of the cyst was a significant independent prognostic factor for resolution A short expectant management is not risky for patients and allows resolution in more than a third of cases
Mandibular advancement oral appliance therapy for obstructive sleep apnoea: effect on awake calibre of the velopharynx
Authors: C F Ryan, L L Love, D Peat, J A Fleetham, A A Lowe
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The mechanisms of action of oral appliance therapy in obstructive sleep apnoea are poorly understood. Videoendoscopy of the upper airway was used during wakefulness to examine whether the changes in pharyngeal dimensions produced by a mandibular advancement oral appliance are related to the improvement in the severity of obstructive sleep apnoea. <h3>METHODS</h3> Fifteen patients with mild to moderate obstructive sleep apnoea (median (range) apnoea index (AI) 4(0–38)/h, apnoea-hypopnoea index (AHI) 28(9–45)/h) underwent overnight polysomnography and imaging of the upper airway before and after insertion of the oral appliance. Images were obtained in the hypopharynx, oropharynx, and velopharynx at end tidal expiration during quiet nasal breathing in the supine position. The cross sectional area and diameters of the upper airway were measured using image processing software with an intraluminal catheter as a linear calibration. <h3>RESULTS</h3> AI decreased to a median (range) value of 0 (0–6)/h (p&lt;0.01) and AHI to 8 (1–28)/h (p&lt;0.001) following insertion of the oral appliance. The median (95% confidence interval) cross sectional area of the upper airway increased by 18% (3 to 35) (p&lt;0.02) in the hypopharynx and by 25% (11 to 69) (p&lt;0.005) in the velopharynx, but not significantly in the oropharynx. Although in general the shape of the pharynx did not change following insertion of the oral appliance, the lateral diameter of the velopharynx increased to a greater extent than the anteroposterior diameter. Following insertion of the oral appliance the reduction in AHI was related to the increase in cross sectional area of the velopharynx (p = 0.01). <h3>CONCLUSIONS</h3> A mandibular advancement oral appliance increases the cross sectional area of the upper airway during wakefulness, particularly in the velopharynx. Assuming this effect on upper airway calibre is not eliminated by sleep, mandibular advancement oral appliances may reduce the severity of obstructive sleep apnoea by maintaining patency of the velopharynx, particularly in its lateral dimension.
A functional SNP in CILP, encoding cartilage intermediate layer protein, is associated with susceptibility to lumbar disc disease
Authors: Shoji Seki, Yoshiharu Kawaguchi, Kazuhiro Chiba, Yasuo Mikami, Hideki Kizawa, Takeshi Oya, Futoshi Mio, Masaki Mori, Yoshinari Miyamoto, Ikuko Masuda, Tatsuhiko Tsunoda, Michihiro Kamata, Toshikazu Kubo, Yoshiaki Toyama, Tomoatsu Kimura, Yusuke Nakamura, Shiro Ikegawa
Journal: Nature Genetics (2005)