tbuckley/cabot-search huggingface dataset:
Effect of oral L-arginine on airway hyperresponsiveness to histamine in asthma
Authors: H W F M de Gouw, M B Verbruggen, I M Twiss, P J Sterk
Journal: Thorax (1999)

Nitric oxide (NO) may exert protective properties within the airways of asthmatic patients. It was postulated that airways obstruction in asthma may be associated with endogenous NO deficiency caused by limited availability of NO synthase substrate.In a double blind, crossover study 14 asthmatic patients received pretreatment with oral L-arginine (50 mg/kg body weight) or placebo prior to histamine challenge. Histamine challenge was performed until a 50% fall in forced expiratory volume in one second (FEV(1)) occurred and the response was expressed as the provocative concentration causing a 20% fall in FEV(1) (PC(20)) and as the dose-response slope (maximal % fall in FEV(1)/cumulative dose (micromol)).Pretreatment with L-arginine did not affect PC(20) histamine (mean change in doubling dose 0.18 (95% confidence interval (CI) -0.36 to 0.71), p = 0.5) but the dose-response slope to histamine was slightly reduced (mean change: 0.7 (95% CI 0.6 to 0. 9), p = 0.016).Oral L-arginine does not influence airway hyperresponsiveness to histamine as reflected by PC(20), although the dose-response slope is slightly reduced in patients with asthma. This indicates only marginal, clinically unimportant limitation of NO synthase substrate in asthma.
Thrombotic thrombocytopenic purpura: Prolonged coma with recovery of neurologic function with intensive plasma exchange
Authors: Arthur E. Frankel, Martin D. Rubenstein, Robert T. Wall
Journal: American Journal of Hematology (1981)

A 45-year-old-woman was presented with fever, microangiopathic hemolytic anemia, thrombocytopenia, purpura, and mental status changes. She was diagnosed as having thrombotic thrombocytopenic purpura (TPP). She was treated with daily plasma exchange and antiplatelet drugs, steroids, and vincristine. This patient had a remarkable course with 18 days of coma on full therapy followed by essentially complete recovery coincident with an increase of the plasma exchange dose to two plasma volumes processed per procedure. The patient has remained well with discontinuation of plasma exchange. We conclude that prolonged coma without evidence of major central nervous system structural lesions in TTP should be treated vigorously and continuously with plasma exchange.
Membrane cholesterol but not putative receptors mediates anandamide-induced hepatocyte apoptosis
Authors: Kamal Krishna Biswas, Krishna Pada Sarker, Kazuhiro Abeyama, Ko-ichi Kawahara, Satoshi Iino, Yasuharu Otsubo, Kazuhiko Saigo, Hiroyuki Izumi, Teruto Hashiguchi, Munekazu Yamakuchi, Kazuyo Yamaji, Ryujin Endo, Kazuyuki Suzuki, Hitoshi Imaizumi, Ikuro Maruyama
Journal: Hepatology (2003)

The endogenous cannabinoid anandamide, a lipid mediator, induces various physiologic events such as vascular relaxation, inhibition of gap–junctions formation, tumor proliferation, neurologic analgesia, and apoptosis. Although increased concentration of anandamide in plasma has been implicated in pathophysiologic states including endotoxin–induced hypotension, the effects of anandamide on hepatocytes still remain unclear. In this study, we present evidence that plasma anandamide concentration is highly increased in severe hepatitis and cirrhosis patients. In addition, concentrations of anandamide within the pathophysiologic range potently induced apoptosis of hepatoma cell line (Hep G2) and primary hepatocytes, suggesting a possible link between increased anandamide level and hepatocyte damage. Anandamide–induced cell death was preceded by G0/G1 cell–cycle arrest, activation of proapoptotic signaling ( i.e. , p38 MAPK and JNK), and inhibition of antiapoptotic signaling ( i.e. , PKB/Akt) pathways. Moreover, anandamide increased susceptibility to oxidative stress–induced hepatocyte damage. In this context, methyl–β–cyclodextrin (MCD), a membrane cholesterol depletor, or mevastatin, an HMG–CoA reductase inhibitor, or N–acetyl cysteine, an antioxidant, potently inhibited the anandamide–induced proapoptotic events and cell death, whereas putative cannabinoid receptor antagonists did not exhibit an inhibitory effect on anandamide–induced cell death. Furthermore, binding assay using polymyxin beads revealed that anandamide could interact with cholesterol. In conclusion, our data suggest that cholesterol present in the cell membrane determines the fate of hepatocytes exposed to anandamide, possibly functioning as an anandamide receptor.
Prevalence and distribution of osteoarthritis in a population from Georgian and early Victorian London.
Authors: H A Waldron
Journal: Annals of the Rheumatic Diseases (1991)

The prevalence of osteoarthritis was calculated in adult skeletons excavated from the crypt of Christ Church, Spitalfields in east London, which was used for burial between 1729 and 1869. Age and sex specific prevalences were also calculated for a subsample of the group for whom age and sex were accurately known from surviving coffin plates. Prevalences were slightly higher in men than in women, except for generalised osteoarthritis. The principal sites affected were the acromioclavicular joints, the facet joints of the spine, and the hands. Osteoarthritis of the large joints was relatively uncommon; osteoarthritis of the hip occurred in 4/360 (1.1%) of men and 10/346 (2.9%) of women and of the knee in 3/360 (0.8%) of men and 18/346 (5.2%) of women. This last difference was statistically significant. A comparison with modern data suggests that the prevalence of osteoarthritis at Spitalfields was lower than in the contemporary population, and some explanations for this apparent difference are considered.
Modulation of hepatic acute phase gene expression by epidermal growth factor and src protein tyrosine kinases in murine and human hepatic cells
Authors: Yanping Wang, Juergen Ripperger, Georg H. Fey, David Samols, Tomek Kordula, Meir Wetzler, Richard A. Van Etten, Heinz Baumann
Journal: Hepatology (1999)

As part of systemic inflammatory reactions, interleukin 6 (IL-6) induces acute phase protein (APP) genes through the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. Epidermal growth factor (EGF), which contributes to the regenerative process after liver injury and also activates STATs, does not induce but attenuates IL-6-stimulated expression of several APP genes in primary mouse hepatocytes. The APP-modifying action of EGF receptor (EGFR) was characterized in HepG2 cells. Although EGF less effectively engages STAT proteins in these cells, it reduces expression of fibrinogen and haptoglobin, but stimulates production of α 1 -antichymotrypsin and induces transcription through the α 1 -antichymotrypsin and C-reactive protein promoter. The stimulatory EGFR signal is insensitive to inhibition of JAKs and appears to involve Src kinases and STAT proteins as shown by inhibition through overexpression of C-terminal Src kinase (Csk) and transdominant negative STAT3, respectively. A mediator role of Src is supported by the ability of c-Src and v-Src to activate STATs and induce transcription through APP promoters. Src kinases have been observed in association with the IL-6 receptor; however, inhibition of Src kinases by Csk enhances IL-6-induced transcription. The Csk effect is attributed to prevention of Src kinases from phosphorylating gp130 at the docking site for the signal-moderating protein tyrosine phosphatase SHP-2. The inhibitory EGFR signal on APP expression correlates with the activation of Erk1 and Erk2. The study shows a dual signaling function for EGFR and suggests that the ratio of receptor-activated STATs and Erks influence the level of stimulated or inhibited expression of individual APPs.
Phase II Trial of Amrubicin for Treatment of Refractory or Relapsed Small-Cell Lung Cancer: Thoracic Oncology Research Group Study 0301
Authors: Sayaka Onoda, Noriyuki Masuda, Takashi Seto, Kenji Eguchi, Yuichi Takiguchi, Hiroshi Isobe, Hiroaki Okamoto, Takashi Ogura, Akira Yokoyama, Nobuhiko Seki, Yoshiko Asaka-Amano, Masao Harada, Akihiro Tagawa, Hiroshi Kunikane, Masanori Yokoba, Kazutsugu Uematsu, Takayuki Kuriyama, Yumi Kuroiwa, Koshiro Watanabe
Journal: Journal of Clinical Oncology (2006)

This multicenter, phase II study was conducted to evaluate the activity of amrubicin, a topoisomerase II inhibitor, against refractory or relapsed small-cell lung cancer (SCLC).SCLC patients with measurable disease who had been treated previously with at least one platinum-based chemotherapy regimen and had an Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible. Two groups of patients were selected: patients who experienced first-line treatment failure less than 60 days from treatment discontinuation (refractory group), and patients who responded to first-line treatment and experienced disease progression > or = 60 days after treatment discontinuation (sensitive group). Amrubicin was administered as a 5-minute daily intravenous injection at a dose of 40 mg/m2 for 3 consecutive days, every 3 weeks.Between June 2003 and December 2004, 60 patients (16 refractory and 44 sensitive) were enrolled. The median number of treatment cycles was four (range, one to eight). Grade 3 or 4 hematologic toxicities comprised neutropenia (83%), thrombocytopenia (20%), and anemia (33%). Febrile neutropenia was observed in three patients (5%). Nonhematologic toxicities were mild. No treatment-related death was observed. The overall response rates were 50% (95% CI, 25% to 75%) in the refractory group, and 52% (95% CI, 37% to 68%) in the sensitive group. The progression-free survival, overall survival, and 1-year survival in the refractory group and the sensitive group were 2.6 and 4.2 months, 10.3 and 11.6 months, and 40% and 46%, respectively.Amrubicin exhibits significant activity against SCLC, with predictable and manageable toxicities; this agent deserves to be studied more extensively in additional trials.
Escherichia coli endotoxin inhibits agonist-mediated cytosolic Ca2+ mobilization and nitric oxide biosynthesis in cultured endothelial cells.
Authors: W F Graier, P R Myers, L J Rubin, H R Adams, J L Parker
Journal: Circulation Research (1994)

Altered release of endothelium-derived relaxing factor/nitric oxide (EDRF/NO) has been proposed as a final common pathway underlying the abnormal vasodilator responses to gram-negative lipopolysaccharide (endotoxin). However, mechanisms responsible for lipopolysaccharide-induced changes in EDRF/NO release from endothelial cells have not been clarified. We evaluated direct effects of Escherichia coli endotoxin on agonist-stimulated cytosolic Ca2+ mobilization and NO biosynthesis in cultured bovine and porcine aortic endothelial cells (ECs). Two methods were used to assay for NO: (1) analysis of NO-induced endothelial levels of cGMP as a biological indicator of NO generation and (2) direct quantitative measurement of NO release (chemiluminescence method). Cytosolic free Ca2+ ([Ca2+]i) was evaluated using fura 2 fluorescence methodology (340/380-nm ratio excitation and 500-nm emission). Incubation of ECs with endotoxin (0.5 microgram/mL, 1 hour plus 1-hour wash) significantly inhibited bradykinin (100 nmol/L)- and ADP (10 mumol/L)-mediated increases in endothelial cell cGMP to 37% and 22% of control responses, respectively. In contrast, endotoxin failed to inhibit the increase in cGMP produced by the non-receptor-dependent Ca2+ ionophore A23187 (1 mumol/L) or sodium nitroprusside (1 mmol/L). Similarly, incubation with endotoxin inhibited ADP-stimulated increases in NO release and EDRF bioactivity to 55% and 56% of control values, respectively, but did not affect A23187-stimulated increases in NO release or EDRF bioactivity. Endotoxin produced significant decreases in both transient and sustained [Ca2+]i responses of ECs to bradykinin and ADP. For example, the initial rapid increase in bovine EC [Ca2+]i in response to bradykinin was reduced to 31% of the initial increases in control cells, and the secondary plateau phase was reduced to only 3% of respective control responses. Concentration-response relation to endotoxin (10(-3)) to 10(0) micrograms/mL) indicated high correlation and similar IC50 values (0.025 and 0.021 micrograms/mL, respectively) for inhibitory effects on cGMP and [Ca2+]i. Endotoxin had no effect on inositol trisphosphate formation ([3H]myo-inositol incorporation) and intracellular Ca2+ release ([Ca2+]i responses in Ca(2+)-free medium) induced by bradykinin. However, agonist-stimulated Mn2+ quenching (index of Ca2+ influx) was significantly attenuated by endotoxin treatment. These studies demonstrate that endotoxin directly decreases agonist (bradykinin and ADP)-mediated biosynthesis and release of EDRF/NO from ECs. These effects can be explained by altered [Ca2+]i mobilization mechanisms, which in turn produce subsequent decreases in activity of the Ca(2+)-calmodulin-dependent constitutive isoform of NO synthase and, ultimately, impairment of agonist-mediated NO release and endothelium-dependent vasodilation.
Respiratory Complications of Infectious Diseases
Authors: T. Anderson
Journal: Thorax (1961)

<h3>Objective</h3> To determine if a programme of progressive resistance exercise, mobilisation and orientation, in addition to usual care, was superior to usual care alone in the prevention of incident delirium in older hospitalised patients. <h3>Design</h3> A randomised controlled trial. <h3>Setting</h3> The study was performed at a secondary referral hospital in Melbourne, Australia between May 2005 and December 2007. <h3>Participants</h3> 648 consecutive medical inpatients aged 65 years or older who had been in hospital for less than 48 h and who did not have delirium. <h3>Intervention</h3> Participants were randomly allocated to a twice-daily programme of progressive resistance exercise tailored to individual ability, mobilisation and orientation in addition to usual care or to usual care alone. <h3>Measurements</h3> Delirium was measured using the Confusion Assessment Method at baseline and every 48 h until discharge. Secondary outcome measures were severity and duration of delirium, discharge destination and length of stay. <h3>Results</h3> Delirium occurred in 4.9% (95% CI 2.3% to 7.3%) of the intervention group (15/305) and in 5.9% (20/339; 95% CI 3.8% to 9.2%) of the group receiving usual care. No difference was observed between groups (χ<sup>2</sup>; p=0.5). The intervention had no effect on delirium duration, severity, discharge destination or length of stay. <h3>Conclusion</h3> A programme of progressive resistance exercise and orientation was not effective in reducing incident delirium in hospitalised elderly patients.
Increased Factor VIII/von Willebrand Factor Antigen and von Willebrand Factor Activity in Scleroderma and in Raynaud's Phenomenon
Authors: M. BASHAR KAHALEH
Journal: Annals of Internal Medicine (1981)

Von Willebrand factor activity and factor VIII/von Willebrand factor (fVIII/vWf) antigen concentrations were evaluated in 17 patients with scleroderma, nine patients with Raynaud's phenomenon, and eight control volunteers. Higher circulating levels of both activities were seen: von Willebrand factor, 374% ± 40% (percent of control values) in scleroderma patients, 502% ± 104% in patients with Raynaud's phenomenon and 102% ± 6% in control subjects (p < 0. 005, scleroderma versus control); fVIII/vWf antigen, 255% ± 24% in scleroderma patients; 271% ± 46% in patients with Raynaud's phenomenon, and 99% ± 4% in control subjects (p < 0.005, scleroderma versus control). Because endothelial cells synthesize and secrete both substances, the role of endothelial injury in vitro was investigated. Wound injury induced a 344% ± 33% increase in von Willebrand factor and a 115% ± 5% increases in fVIII/vWf antigen; cold injury induced 644% ± 66% and 150% ± 10% increases, and cytotoxic endothelial injury induced 1055% ± 83% and 185% ± 20% increases. In five patients with scleroderma, cold exposure led to a further increase in both activities. The observed increase of both activities in scleroderma and Raynaud's phenomenon may reflect in-vivo endothelial injury and regeneration in these related conditions.
Antipsychotics in the treatment of autism
Authors: David J. Posey, Kimberly A. Stigler, Craig A. Erickson, Christopher J. McDougle
Journal: Journal of Clinical Investigation (2008)

Atypical antipsychotics have become indispensable in the treatment of a variety of symptoms in autism. They are frequently used to treat irritability and associated behaviors including aggression and self injury. They may also be efficacious for hyperactivity and stereotyped behavior. This review presents the rationale for the use of this drug class in autism and reviews the most important studies published on this topic to date. Significant adverse effects, including weight gain and the possibility of tardive dyskinesia, are reviewed. Future research directions are discussed.
Transbronchial needle aspiration of a mediastinal mass: therapeutic implications.
Authors: K P Wang, S Nelson, J Scatarige, S Siegelman
Journal: Thorax (1983)

Neoplasms, cysts, inflammatory processes, and aneurysms may present as a mediastinal mass.New diagnostic techni- ques have recently become available for use in the inves- tigation of a mediastinal mass, and we present a case illus- trating the use of a transbronchial needle through a flexible bronchoscope to drain an accumulation of mediastinal fluid.So far as we are aware this is the first such report published in English.
Quality matters in lung cancer diagnosis – Comparison of endobronchial cryobiopsy with conventional forceps biopsy
Authors: Ute Oltmanns, Doris Rassl, Mark Slade
Journal: European Respiratory Journal (2011)

Introduction:  Endoscopic forceps biopsies are often small and inadequate for detailed analysis whereas biopsies obtained with cryoprobes may provide tissue samples that are larger and better preserved. We compared the quality and complication rate of endoscopic forceps- and cryobiopsies.   Methods:  Prospectively collected data of patients who underwent cryobiopsy (CB, n=14) were compared with randomly selected patients who had conventional forceps biopsies (FB) during the same time period (n=13). All patients were considered prospectively to have definite endobronchial tumour. Sample size and quality was assessed. Complication rate and final diagnosis were also recorded.   Results:  Maximum sample diameter was significantly larger in the CB group (median 1.6cm, range 0.7-3.0cm) compared to the FB group (median 0.5cm, range 0.3-1.3cm, p   Conclusions:  Cryobiopsy appears to provide larger and higher-quality tumour specimens than conventional forceps biopsy. These differences may become important in an era of targeted therapies for individual patients, when multiple testing of biopsies is required. We believe the technique of cryobiopsy merits further evaluation.
CD40 Ligand–Dependent Tyrosine Nitration of Prostacyclin Synthase In Vivo
Authors: Bradley Davis, Ming-Hui Zou
Journal: Circulation (2005)

Cells in human atherosclerotic lesions express the immune mediator CD40 and its ligand, CD40L, but the mechanisms and the mediators by which CD40L contributes to atherosclerosis are poorly defined. Here, we show how CD40L increases vascular inflammation and thrombosis via tyrosine nitration and inhibition of prostacyclin synthase (PGIS), an enzyme with antithrombotic, antiproliferative, and dilatory functions in the normal vasculature.Exposure of cultured human aortic endothelial cells to clinically relevant concentrations of CD40L (20 to 80 ng/mL) dose-dependently increased the production of superoxide (O2*-), decreased nitric oxide (NO) bioactivity, and increased PGIS nitration. Furthermore, inhibition of CD40 expression by small interfering RNA blocked the effects of CD40L on O2*-, NO bioactivity, and PGIS nitration, which indicates a specific effect of CD40L. In addition, either depletion of mitochondria (rho0 cells, ie, mitochondria-depleted cells, to prevent mitochondrial O2*-) or adenoviral overexpression of superoxide dismutase, as well as inhibition of NO synthase, abolished the CD40L-enhanced PGIS nitration, which implies that the mitochondria might be the source of O2*- and thus peroxynitrite (ONOO-). Furthermore, SQ29548, a thromboxane A2/prostaglandin H2 receptor antagonist, significantly reduced CD40L-enhanced expression of intercellular adhesion molecule-1. Finally, administration of CD40L resulted in PGIS inhibition and nitration in the aortas of C57BL6 mice but less in mice overexpressing human superoxide dismutase, which suggests that ONOO- might be required for CD40L-enhanced PGIS nitration in vivo.We conclude that CD40L might contribute to the initiation and progression of atherosclerosis by increasing O2*(-)- and ONOO(-)-dependent PGIS nitration and thromboxane A2/prostaglandin H2 receptor stimulation.
Pericardiodesis in pericardial tamponade
Authors: Kalliopi Athanassiadi, Ilias Samiotis, Athanasia Makrygianni, Niki Paparizou, Paraskevi Ntolou, Stamatios Kakaris
Journal: European Respiratory Journal (2014)

OBJECTIVE: The reported prevalence of pericardial diseases has changed and varied according to diagnostic methods. In an autopsy series, it has been found in 2%-4% of the general population, in 7%-12% of cancer patients and, among these, in 19%-40% of patients dying of lung cancer. The goals of treatment may be simply to relieve symptoms and prevent recurrent effusion for a long-term symptomatic benefit, or to treat the local neoplastic disease with the aim of prolonging survival. We present our experience with pericardiodesis in 24 patients.

MATERIAL: During the last 10 years 24 patients with tamponade or large pericardial effusion were admitted to our departments. Only in 7 cases (29%) there was a known history of neoplastic disease. The main symptom was dyspnea and the diagnostic tool of choice was echocardiogram.

RESULTS: All but one patients were led to surgery, submitted to pericardial window and in undiagnosed cases an additional lung and pleural biopsy were performed. A soft foley catheter was introduced though the pericardial window as a pericardial drainage. Histology revealed in the majority of cases lung cancer, in 2 breast cancer (8.3%), in 5 cases (20.8%) inflammatory disease and only in one tuberculosis. In all cases but two pericardiodesis was performed through the foley catheter after instillation of xylocaine. In cases of neoplastic disease the agent of choice was bleocin, while in cases of inflammatory diseases tetracycline was instilled. The postoperative course was unevenful. No recurrences were observed in a follow up of 6.5 months.

CONCLUSION: Pericardiodesis is an easy-to-perform and cost-effective method preventing from recurrences and offering even in end stage neoplastic disease a better quality of life.