tbuckley/cabot-search huggingface dataset:
Anesthesia Not Related to Fludarabine Toxicity
Authors: Roger B. Cohen
Journal: Annals of Internal Medicine (1993)

Letters1 September 1993Anesthesia Not Related to Fludarabine ToxicityRoger B. Cohen, MD and Francine Foss, MDRoger B. Cohen, MDSearch for more papers by this author and Francine Foss, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-5-199309010-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Shepherd is correct that there are no data to support the existence of an interaction between fludarabine and general anesthesia. Our statement was intended as speculation only in considering existing comorbid diseases, procedures, or concomitant medications as potential cofactors in the adverse reaction. Author, Article, and Disclosure InformationAuthors: Roger B. Cohen, MD; Francine Foss, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1993Volume 119, Issue 5Page: 437KeywordsAdverse reactionsAnesthesiaGeneral anesthesiaToxicity ePublished: 15 August 2000 Issue Published: 1 September 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Chemokine blockade and chronic inflammatory disease: proof of concept in patients with rheumatoid arthritis
Authors: J J Haringman
Journal: Annals of the Rheumatic Diseases (2003)

<b>Background:</b> Chemokines and their receptors are considered important contributors in cell migration and inflammation in chronic inflammatory disorders. Chemokines affecting monocytes/macrophages are considered potential therapeutic targets, but no studies of the effects of blocking the chemokine repertoire in humans with a chronic inflammatory disease have been reported. <b>Objective:</b> To carry out a double blind, placebo controlled, phase Ib clinical trial with a specific, oral CCR1 antagonist. <b>Methods:</b> 16 patients with active rheumatoid arthritis (RA) were randomised 3:1 to active:placebo treatment for 14 days. Synovial biopsy specimens were obtained on days 1 and 15. Immunohistochemistry was used to detect the presence of various cell types before and after treatment and the results measured by digital image analysis. Results before and after treatment were compared by paired <i>t</i> test, and a two sample <i>t</i> test was used to compare the changes from baseline in the two groups. <b>Results:</b> All patients completed the study. A significant reduction in the number of macrophages (p=0.016), intimal macrophages (p=0.026), and CCR1+cells (p=0.049) in patients treated with the chemokine antagonist compared with the placebo group occurred in the synovium. Significant decreases in overall cellularity, intimal lining layer cellularity, CD4+ T cells, and CD8+ T cells also occurred in treated patients. Cells lacking CCR1 were not affected. Trends towards clinical improvement were seen in the treated patients but not in the placebo group. Severe side effects were not reported. <b>Conclusion:</b> Specific chemokine receptor blockade can result in relevant biological effects in patients with active RA.
Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis.
Authors: J Neuberger, E Christensen, B Portmann, J Caballeria, J Rodes, L Ranek, N Tygstrup, R Williams
Journal: Gut (1985)

One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or histological features examined, except the serum alanine aminotransferase activity which was greater in those on active treatment. In this trial we have been unable to establish any therapeutic benefit from the drug.
Reduced intracellular magnesium concentrations in asthmatic patients
Authors: A Emelyanov, G Fedoseev, PJ Barnes
Journal: European Respiratory Journal (1999)

Magnesium is important in the regulation of bronchomotor tone, and low dietary intake of magnesium has been associated with airway hyperresponsiveness in epidemiological studies. The concentration of magnesium in serum, erythrocytes and urine in 49 patients with asthma (29 males, aged 15-65 yrs) and in 25 normal subjects (15 males, aged 17-36 yrs) was studied by atomic absorption. Magnesium concentrations were significantly lower in erythrocytes and urine in both atopic (n = 26) and nonatopic (n = 23) asthmatic patients as compared with the control group, whereas serum concentrations did not differ. The concentration of magnesium in erythrocytes was not related to the degree of airway obstruction as measured by forced expiratory volume in one second (FEV1) but was significantly correlated with airway hyperresponsiveness measured as the provocative concentration causing a 20% fall in FEV1 to inhaled acetylcholine (r = 0.64; p<0.05). In addition, a magnesium tolerance test showed increased retention of magnesium (58.9% of administered dose in asthmatic patients compared with 8.9% in normal subjects, p<0.05). In conclusion, the low cellular concentration of magnesium may be associated with airway hyperresponsiveness in asthmatic patients.
Sequential re-analysis of a phase-III clinical trial in non-small cell lung cancer
Authors: N. Donaldson, R.O. Dillman, J. Wallace, A Ortiz-Hurtado
Journal: European Respiratory Journal (2000)

This paper presents a reanalysis of a randomized clinical trial conducted by the Cancer and Leukemia Group B (CALGB, Bethesda, MD, USA). This trial found a significant benefit of combination chemotherapy followed by irradiation (CTRT) in comparison to radiotherapy alone (RT) for the treatment of nonsmall cell lung cancer. The validity of the results obtained and the decision to terminate taken by the CALGB, were assessed using sequential methods. The reliability and efficiency of sequential methods were also assessed for this study. Two sequential designs were used: the triangular and the restricted procedure. Initial analyses were conducted with the data from patients actually recruited, adjusting for important prognostic variables at any interim analysis. As a confirmatory technique, a continuation of the trial was simulated, sampling extra patients under the assumption of no treatment difference, preserving the effect of the prognostic variables. Using the results from the 155 patients recruited by the CALGB (88 deaths at termination and 136 after follow-up), the sample path stayed within the continuation region of both sequential designs considered. An underpowered sequential analysis showed significant superiority of CTRT over RT (95% confidence interval (95% CI) 0.50-0.96, p=0.03 for the triangular; 95% CI 0.37-0.88, p=0.01 for the restricted procedure). Conventional analysis of the follow-up data also showed significant superiority of CTRT. The trial extended with simulated data ended at 60 months with 251 patients (178 deaths), showing significant superiority of CTRT under both designs (95% CI for hazard ratio 0.55-0.97). The two sequential procedures would have led to the same conclusion as that reached by the Cancer and Leukemia Group B, still achieving considerable savings in patients recruited and time over the conventional design. The data simulated under the rather conservative null hypothesis did not reverse the positive result claimed by the Cancer and Leukemia Group B.
Development of Antiretroviral Drug Resistance
Authors: Mark A. Wainberg, Gerasimos J. Zaharatos, Bluma G. Brenner
Journal: New England Journal of Medicine (2011)

Analysis of HIV drug resistance has identified sites on HIV target genes that convey resistance to particular classes of agents. These data may be especially important in designing effective treatment regimens in parts of the world in which non-B subtypes of HIV predominate.
THE LOCALIZED ACTION ON THE SPINAL CORD OF INTRAMUSCULARLY INJECTED TETANUS TOXIN
Authors: George H. Acheson, Oscar D. Ratnoff, Emanuel B. Schoenbach
Journal: The Journal of Experimental Medicine (1942)

Local tetanus limited to one leg was studied in cats after intramuscular injection of tetanus toxin. 1. The electric and mechanical response of the affected muscle after a single stimulus to the intact sensory-motor nerve is greater in amplitude and duration than the response of the corresponding muscle of the unaffected leg (Fig. 1). 2. This augmented response of the muscle is associated with an augmented response arising from the ipsilateral portion of the spinal cord, while the contralateral part of the cord is unaffected, as demonstrated by electrographic records from the motor nerves (Figs. 2 to 5). 3. The augmented muscular response is abolished when the reflex arc is broken, but the augmented response in the spinal cord is independent of changes in the muscle, the neuromuscular junction, the afferent and efferent peripheral nerves, and the dorsal root ganglia. 4. The augmented spinal response develops in the absence of the peripheral signs of local tetanus. Hence the pathogenesis of the altered state in the spinal cord is independent of the peripheral effects of the toxin. 5. In local tetanus, therefore, the toxin injected intramuscularly acts selectively upon the segments of the spinal cord which supply the innervation of the injected area. 6. The augmented spinal response may be prevented by section of the nerve trunks supplying the area of injection prior to the injection of the toxin. 7. It is concluded that in local tetanus the toxin is carried to the spinal cord by way of peripheral nerves.
A Comparison of the Effect of Infused Catecholamines and Certain Affect States
Authors: RICHARD D. CHESSICK, MARVIN BASSAN, SAMUEL SHATTAN
Journal: American Journal of Psychiatry (1966)

Eighteen subjects participated in the collection of data regarding the physiological effects of infused epinephrine, norepinephrine, and placebo and of laboratory-contrived situations of anxiety, pain, and anger. The study was designed to determine whether any parallel patterns would emerge between the physiological effects of the affect states and of the infused drugs. The results present no clear pattern of correlation. Furthermore, the authors conclude that it has thus far been impossible to experimentally produce the affect states of anger, anxiety, or pain so that each is physiologically unique.
Inflammatory Left Ventricular Microaneurysms as a Cause of Apparently Idiopathic Ventricular Tachyarrhythmias
Authors: Cristina Chimenti, Fiorella Calabrese, Gaetano Thiene, Maurizio Pieroni, Attilio Maseri, Andrea Frustaci
Journal: Circulation (2001)

Background — We sought to investigate the arrhythmogenic role, incidence, treatment, and prognosis of inflammatory left ventricular (LV) microaneurysms in patients with apparently idiopathic ventricular tachyarrhythmias. Methods and Results — We studied 156 consecutive patients (71 men, 85 women; mean age, 44.1±11.8 years) with severe ventricular arrhythmias and normal 2D echo cardiac parameters by coronary and ventricular angiography, biventricular endomyocardial biopsy, and electrophysiological study. Polymerase chain reaction was used to detect genomic sequences of enterovirus, adenovirus, Epstein Barr virus, cytomegalovirus, herpes simplex viruses, influenza A and B viruses, and hepatitis C virus in frozen endomyocardial samples. Of these patients, 15 (9.6%) showed angiographic evidence of single or multiple LV microaneurysms. All 15 patients had recurrent episodes of ventricular tachycardia with right bundle-branch block morphology, and the arrhythmias originated within or close to the aneurysms in those patients (n=6) undergoing ventricular mapping. A lymphocytic myocarditis was observed in LV biopsies of all patients and in the right ventricles of 3 patients. Polymerase chain reaction analysis was performed in 12 and viral genomes were found in 5 (42%): hepatitis C virus in 2, enterovirus in 2, and influenza virus A in 1. The patients were treated with antiarrhythmics, and cardiac function was preserved for the next 47±39.5 months of follow-up. No major clinical event was registered, and arrhythmias were successfully treated by antiarrhythmics. Conclusions — Inflammatory LV microaneurysms, often of viral origin, are a consistent cause of apparently idiopathic ventricular arrhythmias. Their prognosis so far has been benign, and aggressive therapeutic strategies have been unnecessary.
Thrombin Receptor Actions in Neonatal Rat Ventricular Myocytes
Authors: Tianrong Jiang, Valery Kuznetsov, Elena Pak, HongLu Zhang, Richard B. Robinson, Susan F. Steinberg
Journal: Circulation Research (1996)

Abstract Previous studies established that thrombin stimulates phosphoinositide hydrolysis and modulates contractile function in neonatal rat ventricular myocytes. The present study further defines the signaling pathways activated by the thrombin receptor and their role in thrombin’s actions in cardiac myocytes. The thrombin receptor–derived agonist peptide (TRAP, a portion of the tethered ligand created by thrombin’s proteolytic activity) stimulates the rapid and transient accumulation of inositol bis- and tris-phosphates (IP 2 and IP 3 , respectively), which is followed by the more gradual and sustained accumulation of inositol monophosphate (IP 1 ). TRAP elicits a larger and more sustained accumulation of IP 1 than does thrombin. Thrombin and TRAP also activate mitogen-activated protein kinase (MAPK) in cultured neonatal rat ventricular myocytes. Differences in the kinetics and magnitude of thrombin- and TRAP-dependent inositol phosphate (IP) accumulation are paralleled by differences in the kinetics and magnitude of thrombin- and TRAP-dependent activation of MAPK. Pretreatment with phorbol 12-myristate 13-acetate (PMA) to downregulate protein kinase C (PKC) attenuates thrombin- and TRAP-dependent activation of MAPK, although small and equivalent effects of thrombin and TRAP to stimulate MAPK persist in PMA-pretreated cells. These results support the notion that the thrombin receptor activates MAPK through PKC-dependent and PKC-independent pathways and that the incremental activation of MAPK by TRAP over that induced by thrombin is the consequence of enhanced activation through the PKC limb of the phosphoinositide lipid pathway. TRAP also increases the beating rate of spontaneously contracting ventricular myocytes and elevates cytosolic calcium in myocytes electrically driven at a constant basic cycle length. The effects of TRAP to modulate contractile function and elevate intracellular calcium are not inhibited by tricyclodecan-9-yl-xanthogenate (D609, to block TRAP-dependent IP accumulation) or pretreatment with PMA (to downregulate PKC). The TRAP-dependent rise in intracellular calcium also is not inhibited by verapamil or removal of extracellular calcium but is markedly attenuated by depletion of sarcoplasmic reticular calcium stores by caffeine. Patch-clamp experiments demonstrate that TRAP elevates intracellular calcium in cells held at a membrane potential of −70 mV. Taken together, these results support the conclusion that the thrombin receptor modulates contractile function by mobilizing intracellular calcium through an IP 3 -independent mechanism and that this response does not require activation of voltage-gated ion channels.
Differentiation Between Balanitis and Carcinoma In Situ Using Reflectance Confocal Microscopy
Authors: Edith Arzberger, Peter Komericki, Verena Ahlgrimm-Siess, Cesare Massone, Dmitry Chubisov, Rainer Hofmann-Wellenhof
Journal: JAMA Dermatology (2013)

Zoon plasma cell balanitis is a benign inflammatory disease of genital skin. It may be difficult to clinically distinguish between balanitis and carcinoma in situ (CIS); thus, a biopsy may be needed to exclude malignant disease. Reflectance confocal microscopy (RCM) is an in vivo imaging method to get morphologic information about architecture and single cells in the skin.To evaluate the ability of RCM to differentiate between balanitis and CIS compared with the gold standard histopathologic methods.Observer blinded study.A referral center.Fifteen patients with balanitis or CIS.Patients were assessed by clinical, histologic, and RCM findings. All lesions were imaged with the Vivascope 1500. In 5 cases of balanitis, the surrounding, noninvolved skin also was evaluated.Local recurrence, nodal metastasis, disease-specific death, overall death.The clinical diagnoses showed 9 cases of balanitis and 6 cases of CIS. With histopathologic analysis, 12 cases of balanitis and cases of CIS were diagnosed, and RCM evaluation confirmed these diagnoses. The most relevant RCM criteria for CIS were atypical honeycomb pattern, disarranged epidermal pattern, and round nucleated cells. Balanitis showed a nucleated honeycomb pattern and vermicular vessels. Scattered small bright cells and round vessels were present in all lesions. The adjacent normal skin showed a typical honeycomb pattern and round papillary vessels.We were able to differentiate between balanitis and CIS. Reflectance confocal microscopy may help to avoid biopsies at this sensitive site.
Dengue virus NS1 protein activates cells via Toll-like receptor 4 and disrupts endothelial cell monolayer integrity
Authors: Naphak Modhiran, Daniel Watterson, David A. Muller, Adele K. Panetta, David P. Sester, Lidong Liu, David A. Hume, Katryn J. Stacey, Paul R. Young
Journal: Science Translational Medicine (2015)

Complications arising from dengue virus infection include potentially fatal vascular leak, and severe disease has been linked with excessive immune cell activation. An understanding of the triggers of this activation is critical for the development of appropriately targeted disease control strategies. We show here that the secreted form of the dengue virus nonstructural protein 1 (NS1) is a pathogen-associated molecular pattern (PAMP). Highly purified NS1 devoid of bacterial endotoxin activity directly activated mouse macrophages and human peripheral blood mononuclear cells (PBMCs) via Toll-like receptor 4 (TLR4), leading to the induction and release of proinflammatory cytokines and chemokines. In an in vitro model of vascular leak, treatment with NS1 alone resulted in the disruption of endothelial cell monolayer integrity. Both NS1-mediated activation of PBMCs and NS1-induced vascular leak in vitro were inhibited by a TLR4 antagonist and by anti-TLR4 antibody treatment. The importance of TLR4 activation in vivo was confirmed by the reduction in capillary leak by a TLR4 antagonist in a mouse model of dengue virus infection. These results pinpoint NS1 as a viral toxin counterpart of the bacterial endotoxin lipopolysaccharide (LPS). Similar to the role of LPS in septic shock, NS1 might contribute to vascular leak in dengue patients, which highlights TLR4 antagonists as a possible therapeutic option.
The Fate of Psychotic Offenders Returned for Trial
Authors: A. LOUIS MCGARRY
Journal: American Journal of Psychiatry (1971)

In a long-term follow-up study in Massachusetts, the author found that most defendants who have been committed as incompetent to stand trial can probably be returned to the courts soon after their hospitalization; that it is in their best interest, unless their charges can be otherwise disposed of, to stand trial as quickly as possible; and that the risk to society posed by their release is no greater, and possibly less, than that of other groups of offenders.
The NOD-Like Receptor NLRP12 Attenuates Colon Inflammation and Tumorigenesis
Authors: Md. Hasan Zaki, Peter Vogel, R.K. Subbarao Malireddi, Mathilde Body-Malapel, Paras K. Anand, John Bertin, Douglas R. Green, Mohamed Lamkanfi, Thirumala-Devi Kanneganti
Journal: Cancer Cell (2011)
Integrative Analysis of Calcium Cycling in Cardiac Muscle
Authors: D. A. Eisner, H. S. Choi, M. E. Díaz, S. C. O’Neill, A. W. Trafford
Journal: Circulation Research (2000)

Abstract —The control of intracellular calcium is central to regulation of contractile force in cardiac muscle. This review illustrates how analysis of the control of calcium requires an integrated approach in which several systems are considered. Thus, the calcium content of the sarcoplasmic reticulum (SR) is a major determinant of the amount of Ca 2+ released from the SR and the amplitude of the Ca 2+ transient. The amplitude of the transient, in turn, controls Ca 2+ fluxes across the sarcolemma and thence SR content. This control of SR content influences the response to maneuvers that modify, for example, the properties of the SR Ca 2+ release channel or ryanodine receptor. Specifically, modulation of the open probability of the ryanodine receptor produces only transient effects on the Ca 2+ transient as a result of changes of SR content. These interactions between various Ca 2+ fluxes are modified by the Ca 2+ buffering properties of the cell. Finally, we predict that, under some conditions, the above interactions can result in instability (such as alternans) rather than ordered control of contractility.
Multinational, double-blind, randomised, placebo-controlled, prospective study of esomeprazole in the prevention of recurrent peptic ulcer in low-dose acetylsalicylic acid users: the LAVENDER study
Authors: Kentaro Sugano, Myung-Gyu Choi, Jaw-Town Lin, Shinya Goto, Yasushi Okada, Yoshikazu Kinoshita, Hiroto Miwa, Chern-En Chiang, Tsutomu Chiba, Masatsugu Hori, Yasushi Fukushima, Hyun-Soo Kim, Chi-Yang Chang, Masataka Date
Journal: Gut (2013)

<h3>Objectives</h3> To evaluate if esomeprazole prevents recurrent peptic ulcer in adult patients with a history of peptic ulcer receiving low-dose acetylsalicylic acid (ASA, aspirin) for cardiovascular protection in East Asia. <h3>Methods</h3> In this prospective, randomised, double-blind, placebo-controlled trial conducted in Japan, Korea and Taiwan, eligible patients receiving low-dose ASA for cardiovascular protection (81–324 mg/day) were randomised to esomeprazole 20 mg/day or placebo for ≤72 weeks. All patients received concomitant mucosal protection (gefarnate 100 mg/day). The primary endpoint was time to ulcer recurrence (Kaplan–Meier analysis). Efficacy findings are presented up to week 48, as per a planned interim analysis within the study protocol. <h3>Results</h3> A total of 364 patients (79.9% men; mean age, 67.1 years) comprised the full analysis set (esomeprazole, n=182; placebo, n=182). There was a statistically significant difference in the time to ulcer recurrence between esomeprazole and placebo (HR 0.09; 96.65% CI 0.02 to 0.41; p&lt;0.001). The estimated ulcer-free rate at week 12 was 99.3% (esomeprazole) and 89.0% (placebo). The high estimated ulcer-free rate for esomeprazole was maintained through to week 48 (98.3% vs 81.2% of placebo-treated patients). No factors, other than female gender, reduced time to ulcer recurrence in addition to the effect of esomeprazole (p&lt;0.001). Treatment with esomeprazole was generally well tolerated. <h3>Conclusions</h3> Daily esomeprazole 20 mg is efficacious and well tolerated in reducing the recurrence of peptic ulcer in East-Asian patients with a history of ulcers who are taking low-dose ASA for cardiovascular protection. <h3>ClinicalTrial.gov identifier</h3> NCT01069939.