tbuckley/cabot-search huggingface dataset:
Late-Onset Schizophrenia and Very-Late-Onset Schizophrenia-Like Psychosis: An International Consensus
Authors: Robert Howard, Peter V. Rabins, Mary V. Seeman, Dilip V. Jeste, the International Late-Onset
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Although schizophrenia is generally regarded as an illness with onset in late adolescence or early adult life, a sizeable minority of patients first become ill in middle or old age. Inconsistencies in diagnostic systems and nomenclature, coupled with a tendency among most schizophrenia researchers to ascribe late-onset psychoses to organic factors, have led to such cases occupying an ambiguous position in relation to schizophrenia. Through systematic review of the literature and publication of a consensus statement from an international group of experts in the field, this article aims to clarify the positions of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis. METHOD: The authors conducted a MEDLINE literature review and developed a consensus statement summarizing the findings from 2 days of debate and discussion by members of the International Late-Onset Schizophrenia Group. RESULTS: The group achieved consensus on diagnosis, nomenclature, treatment guidelines, and future research directions. CONCLUSIONS: In terms of epidemiology, symptom profile, and identified pathophysiologies, the diagnoses of late-onset schizophrenia (illness onset after 40 years of age) and very-late-onset schizophrenia-like psychosis (onset after 60 years) have face validity and clinical utility. General adoption of these categories will foster systematic investigation of such patients.
Cisplatin, Dacarbazine With or Without Subcutaneous Interleukin-2, and Interferon Alfa-2b in Advanced Melanoma Outpatients: Results From an Italian Multicenter Phase III Randomized Clinical Trial
Authors: Ruggero Ridolfi, Vanna Chiarion-Sileni, Michele Guida, Antonella Romanini, Roberto Labianca, Andrea Freschi, Giovanni Lo Re, Rolando Nortilli, Sonia Brugnara, Patrizia Vitali, Oriana Nanni
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Phase II and III studies have shown that the addition of interleukin-2 (IL-2) and interferon alfa-2b (IFNα-2b) in multiagent chemotherapy (CT) for advanced melanoma increases overall response (OR), albeit without clear evidence of an improvement in overall survival (OS). Treatment with high-dose IL-2 can cause severe toxicity and is normally administered in an inpatient setting. We conducted a multicenter prospective randomized clinical trial in outpatients with metastatic melanoma to compare CT with biochemotherapy (bioCT) using immunomodulant doses of IL-2 and IFNα-2b. PATIENTS AND METHODS: One hundred seventy-six eligible patients with advanced melanoma were randomized to receive CT (cisplatin and dacarbazine with or without carmustine every 21 days) or bioCT comprising the same CT regimen followed by low-dose subcutaneous IL-2 for 8 days and IFNα2b three times a week, both for six cycles. RESULTS: At a median follow-up of 18 (CT) and 16 (bioCT) months, median OS was 9.5 versus 11.0 months (P = .51), respectively. In the 89 CT-arm patients, 18 ORs (20.2%) (three complete responders [CRs] and 15 partial responders [PRs]) were observed according to World Health Organization criteria. In the 87 bioCT-arm patients, 22 ORs (25.3%) (three CRs and 19 PRs) (P = .70) were recorded. Treatment-related toxicity was fairly similar in both arms. CONCLUSION: The addition of low-dose immunotherapy did not produce a statistically significant advantage in OS, time to progression, or OR. However, the 11-month median OS in the bioCT arm does not differ greatly from the best results with high-dose IL-2–containing regimens reported in the literature. Furthermore, our treatment schedule was carried out on outpatients and had an acceptable level of toxicity.
Biomechanical insights into the aetiology of infraspinatus syndrome
Authors: Jonathan C Reeser, Glenn S Fleisig, Ann M J Cools, Darcie Yount, Scott A Magnes
Journal: British Journal of Sports Medicine (2012)

Infraspinatus syndrome (IS) results from injury to the suprascapular nerve. For reasons that are poorly understood, volleyball players are at greater risk of developing IS than are athletes who compete in other overhead sports. Differences between the shoulder kinematics of volleyball-related overhead skills and those skills demanded by other overhead sports might explain the pronounced prevalence of IS among volleyball athletes.Observational, laboratory-based, cross-sectional study.The American Sports Medicine Institute.Fourteen healthy female Division 1 collegiate volleyball athletes.Upper limb biomechanics of 14 healthy female Division 1 collegiate volleyball athletes while spiking and serving were quantified, then compared to the results from data previously obtained from female baseball pitchers and tennis players.Although the general movement pattern at the shoulder girdle is qualitatively similar for the upper limb skills required by a variety of overhead sports, volleyball spiking and serving result in greater shoulder abduction and horizontal adduction at the moment of ball contact/release than do baseball pitching or tennis serving.The authors suggest that the unique scapular mechanics which permit the extreme shoulder abduction and horizontal adduction that characterise volleyball spiking and serving place anatomically predisposed volleyball athletes at increased risk for developing cumulative traction-related injury to the suprascapular nerve at the level of the spinoglenoid notch.
X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo
Authors: Zhensheng Zhang, Nobuyuki Torii, Zongyi Hu, James Jacob, T. Jake Liang
Journal: Journal of Clinical Investigation (2001)

The X protein (HBX) of the hepatitis B virus (HBV) has been shown to be important for the establishment of HBV infection in vivo. Our previous studies suggested that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. In this study, we generated a series of woodchuck hepatitis virus (WHV) X mutants, including mutants of the domain interacting with the proteasome, and studied their infectivity in woodchucks. Many of the mutants were defective in transactivation but none of them were completely replication defective in vitro. In vivo, all the wild-type and some X mutant–transfected animals demonstrated evidence of infection with anti-WHc and/or anti-WHs seroconversion. Most of the wild-type– and X mutant–transfected animals had transient viremia. Some animals were later challenged with infectious WHV. Animals inoculated with X mutants, including those with no serologic evidence of infection, were protected from the challenge, suggesting previous infection with resulting protective immunity. Our study demonstrates that the previously described functional domains of HBX are biologically important and the X-defective mutants, possibly as attenuated viruses, are not completely replication defective in vivo.
Effect of frusemide on cough responses to chloride-deficient solution in normal and mild asthmatic subjects
Authors: RA Stone, PJ Barnes, KF Chung
Journal: European Respiratory Journal (1993)

We studied the tussive effects of a chloride-deficient solution (1.26% sodium bicarbonate). Nine normal volunteers and 10 mild asthmatic subjects were studied. In two double-blind, placebo-controlled, cross-over studies, we assessed the profile of any inhibitory effects that inhaled frusemide had over these responses. Baseline cough challenge was followed by inhalation of either frusemide (40 mg), or 0.15 M NaCl control. Cough was then induced at 0.5, 2, 4 and 6 h after treatment. Forced expiratory volume in one second (FEV1) was measured before and after each challenge. Changes from the baseline cough response due to drug or control were compared nonparametrically at each time point. There was no difference in the sensitivity of normal and asthmatic subjects to the cough challenge (median cough response 15 and 14.5 on control day, 12 and 15 on frusemide day). Frusemide caused sustained inhibition of the cough response in normal subjects (p < 0.05 at 2 h, p < 0.01 at 4 h), but had only a small, nonsignificant effect in asthmatic subjects at 30 min. Falls in FEV1 of asthmatic subjects due to the chloride-deficient solution were not significant, and did not correlate with number of coughs. We conclude that mild asthmatic subjects are less sensitive than normal subjects to the influence of frusemide against low chloride challenge. This observation is not explained by bronchoconstrictor effects of the cough challenge in asthmatic subjects.
When can a professional athlete return to play following scapholunate ligament delayed reconstruction?
Authors: Ashleigh Williams, Chye Yew Ng, Michael J Hayton
Journal: British Journal of Sports Medicine (2013)

The aim of this study was to determine the outcomes in relation to return-to-play in professional athletes who had undergone a delayed scapholunate ligament reconstruction.We searched our prospectively managed database and identified 15 professional athletes who had undergone the modified Brunelli procedure for scapholunate instability. They were contacted to complete a telephone interview. We established the duration between the operation and return-to-play, the level of competition before and after the procedure and if applicable, reasons for reduction in the level of competition.Between 2008 and 2011, 15 professional male athletes underwent the modified Brunelli procedure. One was lost to follow-up and 14 athletes (11 rugby, 2 boxing and 1 golf) were contactable. The mean age of the patients was 30 years (range 18-42). The mean follow-up period was 25 months (range 3-43). Eleven of the 14 (79%) athletes returned to play within 4 months of surgery. By the final review, 9 of the 14 (64%) athletes had returned to play at their preinjury level of competition.A majority (approximately 80%) of professional athletes return to competitive playing within 4 months of undergoing a scapholunate ligament reconstruction. Approximately two-thirds return to play at their preinjury level of competition.
Effects of smoking on renal hemodynamics in healthy volunteers and in patients with glomerular disease.
Authors: E Ritz, U Benck, E Franek, C Keller, M Seyfarth, J Clorius
Journal: Journal of the American Society of Nephrology (1998)

Patients with renal disease who smoke have a poor renal functional prognosis, but the mechanisms involved have not been explored. In this controlled study, the effects of smoking and sham smoking were compared in 15 healthy normotensive volunteers. All were occasional smokers and abstained from smoking for 48 h as documented by urinary cotinine measurements. These data were compared with those of seven patients with biopsy-confirmed IgA glomerulonephritis, also occasional smokers. Renal clearance examinations were obtained after hydration in the supine position before and while smoking two cigarettes or sham cigarettes in random order on 2 consecutive days. GFR and effective renal plasma flow were determined using In111-diethylenetriamine penta-acetic acid and 131I-hippurate with a dual tracer infusion clearance technique. In an ancillary study with six volunteers, the effect of smoking was compared with the effect of nicotine-containing chewing gum. In healthy volunteers, sham smoking caused a minor but significant increase of mean arterial pressure (MAP) and GFR with no significant change of effective renal plasma flow, filtration fraction (FF), or renovascular resistance. Smoking caused a significant and more marked increase of MAP (from baseline 92.8+/-8.98 to 105+/-7.78 mmHg) and heart rate (from 61.7+/-7.52 to 86.4+/-9.87 min(-1)), accompanied by a significant increase in arginine vasopressin (from 1.27+/-0.72 to 19.9+/-27.2 pg/ml) and epinephrine (from 37+/-13 to 140+/-129 pg/ml). During smoking, GFR decreased in all but one volunteer (from 120+/-17.7 to 102+/-19.3 ml/min per 1.73 m2), and this was accompanied by a significant decrease of FF (from 21.3+/-4.24 to 17.4+/-3.41%) and an increase in renovascular resistance (from 97.6+/-27.2 to 108+/-30.4 mmHg x min/ml per 1.73 m2). These findings were reproduced with nicotine-containing chewing gum. In contrast, when patients with IgA glomerulonephritis smoked, a similar increment in MAP was noted, the changes of FF were not uniform, and a small but consistent increase of urinary albumin/creatinine ratio was observed. An additional 20 volunteers were subjected to the smoking arm of the study for statistical evaluation of the GFR change in patients. The difference between the change of GFR between all volunteers (n = 35) and patients (n = 7) was significant (P < 0.005). It is concluded that the known effects of smoking and nicotine on the sympathetic nervous system and on systemic hemodynamics are accompanied by significant acute changes in renal hemodynamics and albuminuria. These findings are of interest because of the known effects of smoking on progression of renal disease.
Inhalation of china stone and china clay dusts: relationship between the mineralogy of dust retained in the lungs and pathological changes.
Authors: J C Wagner, F D Pooley, A Gibbs, J Lyons, G Sheers, C B Moncrieff
Journal: Thorax (1986)

A combined clinical, radiological, pathological, and mineralogical study was undertaken on 62 cases referred to the Medical Research Council Pneumoconiosis Unit by the Cardiff Pneumoconiosis Panel as Cornish china clay workers. Considerable pathological lesions were found in the lungs, both nodular and interstitial fibroses being present. Some men had worked with china stone but others had worked entirely with china clay. Nodular fibrosis appeared to be related to a high quartz content of the dust recovered from the lung, whereas among those with a high content of kaolinite dust in the lungs interstitial fibrosis was observed.
Effects of Lipid Lowering by Pravastatin on Progression and Regression of Coronary Artery Disease in Symptomatic Men With Normal to Moderately Elevated Serum Cholesterol Levels
Authors: J. Wouter Jukema, Albert V.G. Bruschke, Ad J. van Boven, Johan H.C. Reiber, Egbert T. Bal, Aeilko H. Zwinderman, Hans Jansen, Geert J.M. Boerma, Feikje M. van Rappard, Kong I. Lie
Journal: Circulation (1995)

Background Intensive lowering of serum cholesterol may retard progression of coronary atherosclerosis in selected groups of patients. However, few data are available on the potential benefit of serum cholesterol reduction in the broad range of patients with coronary atherosclerosis and normal to moderately elevated serum cholesterol levels who undergo various forms of treatment. The Regression Growth Evaluation Statin Study (REGRESS) addresses this group of patients. Methods and Results REGRESS is a double-blind, placebo-controlled multicenter study to assess the effects of 2 years of treatment with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on progression and regression of coronary atherosclerosis in 885 male patients with a serum cholesterol level between 4 and 8 mmol/L (155 and 310 mg/dL) by quantitative coronary arteriography. Primary end points were (1) change in average mean segment diameter per patient and (2) change in average minimum obstruction diameter per patient. Clinical events were also analyzed. Of the 885 patients, 778 (88%) had an evaluable final angiogram. Mean segment diameter decreased 0.10 mm in the placebo group versus 0.06 mm in the pravastatin group ( P =.019): The mean difference between treatment groups was 0.04 mm, with a 95% CI of 0.01 to 0.07 mm. The median minimum obstruction diameter decreased 0.09 mm in the placebo group versus 0.03 mm in the pravastatin group ( P =.001): The difference of the medians between the treatment groups was 0.06 mm, with a CI of 0.02 to 0.08 mm. At the end of the follow-up period, 89% (CI, 86% to 92%) of the pravastatin patients and 81% (CI, 77% to 85%) of the placebo patients were without new cardiovascular events ( P =.002). Conclusions In symptomatic men with significant coronary atherosclerosis and normal to moderately elevated serum cholesterol, less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group.
Antineutrophil Cytoplasmic Autoantibodies Interact with Primary Granule Constituents on the Surface of Apoptotic Neutrophils in the Absence of Neutrophil Priming
Authors: Hannah M. Gilligan, Brunel Bredy, Hugh R. Brady, Marie-Josée Hébert, Henry S. Slayter, Yuhui Xu, Joyce Rauch, Michael A. Shia, Jason S. Koh, Jerrold S. Levine
Journal: The Journal of Experimental Medicine (1996)

The pathogenic role of antineutrophil cytoplasmic autoantibodies (ANCA) remains controversial because of the difficulty in explaining how extracellular ANCA can interact with intracellular primary granule constituents. It has been postulated that cytokine priming of neutrophils (PMN), as may occur during a prodromal infection, is an important trigger for mobilization of granules to the cell surface, where they may interact with ANCA. We show by electron microscopy that apoptosis of unprimed PMN is also associated with the translocation of cytoplasmic granules to the cell surface and alignment just beneath an intact cell membrane. Immunofluorescent microscopy and FACS® analysis demonstrate reactivity of ANCA-positive sera and antimyeloperoxidase antibodies with apoptotic PMN, but not with viable PMN. Moreover, we show that apoptotic PMN may be divided into two subsets, based on the presence or absence of granular translocation, and that surface immunogold labeling of myeloperoxidase occurs only in the subset of PMN showing translocation. These results provide a novel mechanism that is independent of priming, by which ANCA may gain access to PMN granule components during ANCA-associated vasculitis.
Behavior of right and left ventricles during episodes of variant angina in relation to the site of coronary vasospasm.
Authors: D Neglia, O Parodi, P Marzullo, G Sambuceti, C Marcassa, C Michelassi, A L'Abbate
Journal: Circulation (1990)

The effects of single-vessel coronary occlusion on simultaneously evaluated right (RV) and left ventricular (LV) performance were assessed and compared with LV perfusion patterns in 25 patients with variant angina. Coronary spasm involved the right coronary artery in 15 patients (group 1) and the left anterior descending coronary artery in 10 patients (group 2). Biventricular function was assessed by radionuclide angiography under basal conditions, during spontaneous or ergonovine-induced ischemia, and after resolution of the ischemic attack. Myocardial perfusion was assessed by thallium 201 scintigraphy in 21 patients of this series during superimposable ischemic episodes. In group 1, ischemia caused RV (14 of 15 patients) and LV (13 of 15 patients) regional dysfunction with significant reduction in RV and LV ejection fractions. The interventricular spetum was involved in six of 15 patients, causing a more pronounced LV impairment. In group 2, all patients showed septal dyssynergies associated with a reduction of LV ejection fraction; absent or trivial RV involvement was observed. In both groups, LV perfusion defects were present in all patients with LV wall motion abnormalities during ischemia, matching the site of regional dyssynergies. Thus, in a group of patients with variant angina and single-vessel disease, transient occlusion of the right coronary artery directly caused RV and LV impairment; in these patients, the extent of LV but not RV dysfunction appeared related to the presence of septal ischemia. Vasospasm of the left anterior descending coronary artery consistently caused LV dysfunction not associated with secondary effects on RV systolic function.
Suppressive Effects of Statins on Acute Promyelocytic Leukemia Cells
Authors: Antonella Sassano, Efstratios Katsoulidis, Giovanni Antico, Jessica K. Altman, Amanda J. Redig, Saverio Minucci, Martin S. Tallman, Leonidas C. Platanias
Journal: Cancer Research (2007)

Abstract The family of statins includes pharmacologic inhibitors of the 3-hydroxy-3-methylglutaryl-CoA reductase that are potent regulators of cholesterol biosynthesis. In addition to their cholesterol-lowering effects, statins inhibit cell proliferation and promote apoptosis of malignant cells in vitro, but their potential therapeutic roles in the treatment of malignancies remain to be defined. We examined the effects of statins on the growth and differentiation of acute myeloid leukemia (AML) cells. Atorvastatin and fluvastatin were found to be potent inducers of cell differentiation and apoptosis of the NB4 acute promyelocytic leukemia (APL) cell line. Such effects correlated with activation of the small G-proteins Rac1/Cdc42 and downstream engagement of the c-Jun NH2-terminal kinase kinase pathway, whose function was found to be essential for the generation of proapoptotic responses. Importantly, different statins were found to enhance all-trans-retinoic acid (ATRA)–dependent differentiation of APL blasts and reverse resistance to the antileukemic effects of ATRA. In addition, fluvastatin exhibited growth-inhibitory properties on primary bone marrow–derived leukemic progenitors from patients with AML and enhanced the suppressive effects of ATRA on leukemic progenitor colony formation. Altogether, these studies establish that statins exhibit potent antileukemic properties in vitro and raise the possibility that combinations of statins with ATRA may be an effective approach to overcome the development of ATRA resistance by the leukemic cells. [Cancer Res 2007;67(9):4524–32]
Different mechanisms underlying the stimulation of KCa channels by nitric oxide and carbon monoxide
Authors: Lingyun Wu, Kun Cao, Yanjie Lu, Rui Wang
Journal: Journal of Clinical Investigation (2002)

The molecular mechanisms underlying the effects of nitric oxide (NO) and carbon monoxide (CO), individually and collectively, on large-conductance calcium-activated K+ (KCa) channels were investigated in rat vascular smooth muscle cells (SMCs). Both NO and CO increased the activity of native KCa channels. Dehydrosoyasaponin-I, a specific agonist for β subunit of KCa channels, increased the open probability of native KCa channels only when it was delivered to the cytoplasmic surface of membrane. CO, but not NO, further increased the activity of native KCa channels that had been maximally stimulated by dehydrosoyasaponin-I. After treatment of SMCs with anti–KCa,β subunit antisense oligodeoxynucleotides, the stimulatory effect of NO, but not of CO, on KCa channels was nullified. CO, but not NO, enhanced the KCa current densities of heterologously expressed cloned KCa,α subunit, showing that the presence of KCa,β subunit is not a necessity for the effect of CO but essential for that of NO. Finally, pretreatment of SMCs with NO abolished the effects of subsequently applied CO or diethyl pyrocarbonate on KCa channels. In summary, the stimulatory effects of CO and NO on KCa channels rely on the specific interactions of these gases with KCa,α and KCa,β subunits.