Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

A study of empyema thoracis and role of intrapleural streptokinase in its management

BACKGROUND: Clinical spectrum, microbiology and outcome of empyema thoracis are changing. Intrapleural instillation of fibrinolytic agents is being increasingly used for management of empyema thoracis. The present study was carried out to describe the clinical profile and outcome of patients with empyema thoracis including those with chronic empyema and to study the efficacy and safety of intrapleural streptokinase in its management. METHODS: Clinical profile, etiological agents, hospital course and outcome of 31 patients (mean age 40 ± 16 years, M: F 25: 6) with empyema thoracis treated from 1998 to 2003 was analyzed. All patients were diagnosed on the basis of aspiration of frank pus from pleural cavity. Clinical profile, response to therapy and outcome were compared between the patients who received intrapleural streptokinase (n = 12) and those who did not (n = 19). RESULTS: Etiology was tubercular in 42% of the patients (n = 13) whereas the rest were bacterial. Amongst the patients in which organisms could be isolated (n = 13, 42%) Staphylococcus aureus was the commonest (n = 5). Intrapleural streptokinase was instilled in 12 patients. This procedure resulted in increase of drainage of pleural fluid in all patients. Mean daily pleural fluid drainage after streptokinase instillation was significantly higher for patients who received intrapleural streptokinase than those who did not (213 ml vs 57 ml, p = 0.006). Only one patient who was instilled streptokinase eventually required decortication, which had to be done in five patients (16.1%). Mean hospital stay was 30.2 ± 17.6 days whereas two patients died. CONCLUSIONS: Tubercular empyema is common in Indian patients. Intrapleural streptokinase appears to be a useful strategy to preserve lung function and reduce need for surgery in patients with late stage of empyema thoracis

Clinical need for sleep monitoring

For all mammals sleep is very essential. A number of diseases cause clinical daytime symptoms primarily through the fragmentation of the sleep process. The most common of these disorders are respiratory which include obstructive sleep apnoea and its variants and Cheyne-Stokes breathing. Among these respiratory disorders, obstructive sleep apnoea has been widely addressed. Up to the present, significant efforts are being exerted to develop the most appropriate treatment for this disease

Pleural disease (excluding malignancy)

Pleural disease is a common medical problem frequently encountered by both respiratory specialists and general physicians. A systematic approach to the patient with a pleural effusion or pneumothorax may avoid unnecessary investigations and reduce patient morbidity. This review focuses on the clinical assessment, diagnosis and management of patients with non-malignant pleural disease and provides some practical suggestions for the practising clinician. © 2008 Elsevier Ltd. All rights reserved

Management of pleural effusions in acute medical settings: A practical guide

In the setting of acute medical care, pleural effusions are often overlooked. This article aims to provide a practical guide for the initial workup of pleural effusions and the management of common types of effusions

Studies on the Structure and Photochemistry of Bacteriorhodopsin (Proton Pumping, Cation Binding, Synthetic Pigments)

231 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1985.Cation Binding By Bacteriorhodopsin (bR). bR normally has a purple color ((lamda)(,max) = 558 nm), hence the name, purple membrane. Atomic absorption spectrophotometry shows that purple membrane binds approximately 4 Ca('++) and Mg('++) per bR at pH = 6.0. Ca('++) and Mg('++) can be removed by various methods from their binding sites. After removal bR turns blue ((lamda)(,max) = 603 nm, the blue membrane).Blue membrane has its own photocycle, having a blue-shifted intermediate with a maximum at 500-510 nm in the millisecond time scale. When Ca('++) and Mg('++) are replaced by La('+++), the kinetics of the M intermediate and proton pumping are significantly changed, drastically so at high pH.Ca('++) and Mg('++) also play an important role in pigment regeneration. In the absence of Ca('++) and Mg('++) the rate of pigment regeneration becomes slower and 430/460 nm regeneration intermediate is absent; moreover, isomeric specificity is altered so that in addition to all-trans and 13-cis isomers, 11-cis retinal could also form a pigment.Divalent cations may bind to the membrane through surface potential or via a specific conformation of coordination ligands like those found in the binding of Ca('++) to calmodulin. Temperature experiments of purple membrane and elemental analysis of bleached membrane show that in addition to the surface potential, a specific conformation of the protein is required for the divalent cation binding.Synthetic Pigments. Acyclic retinal analogues and analogues varying in polyene chain length are used to study the mechanism of pigment formation and the role of the cyclohexyl ring and polyene chain in the function of bR. The results indicate that (1) unlike rhodopsin, there is no cyclohexyl ring binding site in bacterioopsin. (2) in order to form a pigment, the chromophore must contain at least three ethylene bonds in the polyene chain. (3) if polyene chain contains four or five ethylenic bonds, a pigment is formed which photocycles and pumps protons. (4) the cyclohexyl ring has no role important in the physiological functions of bR.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

The systemic fibrinolytic activity of intra-pleural streptokinase in humans

A recent controlled trial has shown that intra-pleural streptokinase improves the tube drainage of infected pleural fluid (AJRCCM 1996:153(4): A462). Studies of crude indices of coagulation suggest this benefit is accompanied by little systemic fibrinolysis. To improve the estimation of the risks of intra-pleural streptokinase in humans, thi study examines its systemic fibrinolytic activity in detail. Eight patients (5M 3F, age 38, range 19-76) receiving 250,000 i.u. intra-pleural streptokinase to aid drainage of a loculated or infected pleural effusion were studied. In all subjects pleural drainage was via 14 French catheter flushed four times daily to maintain catheter patency and otherwise kept on -20 cmH2O suction. Streptokinase was introduced dissolved in 30 mls 0.9% saline and retained in the pleural cavity for two hours. Blood was taken before streptokinase administration for fibrinogen (FIB) and D-dimers due to fibrin degradation (DD), prothrombin (INR), activated partial thromboplastin (APTT) and thrombin (TT) ratios. These end points were remeasured at 5 and 24 hours after the administration of streptokinase. There were no changes of either statistical or physiological significance in any end point at 5 or 24 hours post-streptokinase (paired t-test). The baseline and averaged results (5 and 24 hour samples averaged together) are presented in the table. Baseline (SD) Mean (SD) after SK diff. (SD) paired t-test significance INR 1.24(0.11) 1.22(0.21) -0.02(0.25) p >0.8 APTT 1.01(018) 0.99(0.10) -0.02(0.13) p >0.6 TT 1.00(0.07) 0.88(0.31) -0.12(0.30) p >0.3 FIB gl-1 3.57(0.77) 3.86(0.68) 0.31(0.61) p >0.15 DD mcg ml-1 <0.6(0) <0.6(0) 0.00(0.00) p >0.9 250,000 i.u. of intra-pleural streptokinase produces no detectable systemic fibrinolysis in humans