Job satisfaction and occupational stress among general practitioners — a pilot study

Questionnaires assessing levels of job satisfaction and possible sources of stress were distributed to a random sample of general practitioners in the Greater Manchester area. The highest levels of job satisfaction were reported for `intrinsic' job factors such as freedom to choose method of working, amount of responsibility and amount of variety, rather than `extrinsic' factors such as rate of pay and hours of work. The main causes of stress appeared to be interruptions of various kinds. Factor analysis revealed four major sources of stress: interruptions; emotional involvement; administrative workload and work/home interface; and routine medical work. Of these, all but routine medical work were associated with job satisfaction. It is concluded that the major sources of stress for the general practitioner are not medical, but social.     

Penicillium marneffei--an indicator disease of AIDS: a case report

Penicillium marneffei (PM), the only dimorphic species of the genus penicillium is the etiological agent of penicilliosis marneffei. This opportunistic fungal infection occurs among human immunodeficiency virus (HIV) infected and other immunocompromised patient in several regions of South-east Asia, where the infection is considered as an indicator disease of AIDS. A case of penicilliosis marneffei is reported in a patient whose HIV status was unknown and later turned to be in the late stage of AIDS. This demonstrates that it is indeed an indicator disease of AIDS. In India, penicilliosis has been reported among the inhabitants of Manipur state where the prevalence of HIV infection / AIDS is very high. The causative agent was first isolated from a captive bamboo rat. Investigation of the prevalence of the organism among bamboo rats of different countries of South East Asia revealed four species of bamboo rats to be harboring the organism. These four species of bamboo rats are Rhizomys sinensis, R. pruinosus, R. sumatrensis and Cannomys badius. In Manipur, Penicillium marneffei has been isolated from Cannomys badius. Any patient presenting with penicilliosis marneffei should be subjected to HIV counselling and testing if the HIV status is not known and further study regarding the ecology and epidemiology of the fungus is needed.     

Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization,safety and protection against challenge with Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), has infected approximately two billion individuals worldwide with approximately 9.2 million new cases and 1.6 million deaths annually. Current efforts are focused on making better BCG priming vaccines designed to induce a comprehensive and balanced immunity followed by booster(s) targeting a specific set of relevant antigens in common with the BCG prime. We describe the generation and immunological characterization of recombinant BCG strains with properties associated with lysis of the endosome compartment and over-expression of key Mtb antigens. The endosome lysis strain, a derivative of BCG SSI-1331 (BCG₁₃₃₁) expresses a mutant form of perfringolysin O (PfoA_G137Q), a cytolysin normally secreted by Clostridium perfringens. Integration of the PfoA_G137Q gene into the BCG genome was accomplished using an allelic exchange plasmid to replace ureC with pfoA_G137Q under the control of the Ag85B promoter. The resultant BCG construct, designated AERAS-401 (BCG₁₃₃₁ ΔureC::ΩpfoA_G137Q) secreted biologically active Pfo, was well tolerated with a good safety profile in immunocompromised SCID mice. A second rBCG strain, designated AFRO-1, was generated by incorporating an expression plasmid encoding three mycobacterial antigens, Ag85A, Ag85B and TB10.4, into AERAS-401. Compared to the parental BCG strain, vaccination of mice and guinea pigs with AFRO-1 resulted in enhanced immune responses. Mice vaccinated with AFRO-1 and challenged with the hypervirulent Mtb strain HN878 also survived longer than mice vaccinated with the parental BCG. Thus, we have generated improved rBCG vaccine candidates that address many of the shortcomings of the currently licensed BCG vaccine strains.     

Characterization of three abnormal factor IX variants (Bm Lake Elsinore, Long Beach, and Los Angeles) of hemophilia-B. Evidence for defects affecting the latent catalytic site.

Abnormal factor IX variant proteins were isolated from the plasmas of three unrelated severe hemophilia-B families that had been previously shown to contain functionally impaired molecules immunologically similar to normal factor IX. The families studied were: (1) a patient with markedly prolonged ox brain prothrombin time, designated factor IX Bm Lake Elsinore (IXBmLE); (b) three patients (brothers) with moderately prolonged ox brain prothrombin time, designated factor IX Long Beach (IXLB); and (c) a patient with normal ox brain prothrombin time designated factor IX Los Angeles (IXLA). Each variant molecule comigrates with normal factor IX (IXN) both in the sodium dodecyl sulfate and in the nondenaturing alkaline gel electrophoresis. All three variant proteins are indistinguishable from IXN in their amino acid compositions, isoelectric points, carbohydrate distributions and number of gamma-carboxyglutamic acid residues. Each variant protein undergoes a similar pattern of cleavage by factor XIa/Ca2+ and by factor VIIa/Ca2+/tissue factor, and is activated at a rate similar to that observed for IXN. All of the three variant proteins also react with an anti-IXN monoclonal antibody that interferes with the binding of activated IXN(IXaN) to thrombin-treated factor VIIIC. However, in contrast to IXaN, the cleaved IXBmLE has negligible activity (approximately 0.2%), and cleaved forms of IXLA and IXLB have significantly reduced activity (approximately 5-6%) in binding to antithrombin-III/heparin, and in activating factor VII (plus Ca2+ and phospholipid) or factor X (plus Ca2+ and phospholipid) +/- factor VIII. These data, taken together, strongly indicate that the defect in these three variant proteins resides near or within the latent catalytic site. This results in virtually a complete loss of catalytic activity of the cleaved IXBmLE molecule and approximately 95% loss of catalytic activity of the cleaved IXLA and IXLB molecules.     

Poly(hydrosilane)s as Sources of Silyl Radicals and Their Use as Polymerization‐Initiating Structures

Poly(hydrosilane)s, [R(H)Si]_n [R = Ph, Si(CH₂)₃SiMe₂Th, cy‐Hex], are investigated as sources of silyl radicals. The Si–H bonds in these oligomers exhibit good to excellent hydrogen donating properties which ensure the formation of reactive silyl radicals. For free radical photopolymerization, the polymerization initiating properties of these structures are checked. These polymers are found to be advantageous to overcome the classical oxygen inhibition of the FRP process. Their ability in FRPCP is also evaluated for an epoxy monomer. The mechanisms are investigated through ESR and laser flash photolysis experiments.

     

The safety of post-exposure vaccination of mice infected with Mycobacterium tuberculosis

New post-exposure tuberculosis vaccination strategies are being developed to prevent disease in individuals latently infected with Mycobacterium tuberculosis. However, concerns about the potential induction of deleterious Koch-like reactions after immunization of persons with latent tuberculosis has limited progress in assessing the effectiveness of post-exposure vaccination. To evaluate the safety of immunization after M. tuberculosis infection, two mouse models were established, a drug treatment low bacterial burden model and an active disease model. Twelve different M. tuberculosis antigen preparations and vaccines (including DNA, subunit, viral vectored, and live, attenuated vaccines) were evaluated using these mouse models. In the low bacterial burden model, post-exposure vaccination did not induce significant reactivational disease and only injection of BCG evoked increases in lung inflammatory responses at 1 month after the immunizations. Additionally, although significant increases in lung inflammation were seen for animals injected with the hps65 DNA vaccine or a M. tuberculosis culture supernatant preparation, no differences in the survival periods were detected between vaccinated and non-vaccinated mice at 10 months post-immunization using the low bacterial burden model. For the active disease model, significantly more lung inflammation was observed at 1 month after administration of the hsp65 DNA vaccine but none of the antigen preparations tested increased the lung bacterial burdens at this early time point. Furthermore, vaccination of diseased mice with BCG or TB DNA vaccines did not significantly affect mortality rates compared to non-vaccinated controls at 10 months post-immunization. Overall, these data suggest that while the potential risk of inducing Koch-like reactions is low after immunization of persons with latent tuberculosis, extreme caution is still needed as post-exposure vaccines progress from pre-clinical experiments into the initial phases of clinical testing.     

Efficacy of preoxygenation using tidal volume and deep breathing techniques with and without prior maximal exhalation

PURPOSE: We evaluated the influence of prior maximal exhalation on preoxygenation in 15 adult volunteers using tidal volume breathing (TVB) for five minutes and deep breathing (DB) for two minutes with and without prior maximal exhalation. METHODS: Inspired and end-tidal oxygen, nitrogen and carbon dioxide were monitored continuously and recorded during room air breathing and at 30-sec intervals during 100% oxygen TVB or DB (rate of 8 breaths.min(-1)). RESULTS: Tidal volume breathing with prior maximal exhalation resulted in an end-tidal oxygen concentration (ETO(2)) slightly higher (P = 0.028) at 0.5 and 1.0 min as compared with TVB without prior maximal exhalation at the same time periods. Regardless of whether TVB was preceded by maximal exhalation or not, 2.5 min was required to reach a mean ETO(2) value of 90% or higher. With DB, there were no differences in ETO(2) values at any time period and 1.5 min was required to reach an ETO(2) of 90% or greater, with or without prior maximal exhalation. CONCLUSIONS: Maximal exhalation prior to TVB slightly steepens the initial rise in ETO(2) during the first minute, but confers no real benefit if maximal preoxygenation is the goal. Maximal exhalation prior to DB has no added value in enhancing preoxygenation.     

A colorimetric assay for viral agents that produce cytopathic effects

Many animal viruses produce cytopathic effects in their host cells during a productive infection. While some virus infections can be assayed by the production of plaques, many viruses, while producing cytotoxicity, do not easily form plaques, or do not form plaques at all. Additionally, viruses within families such as the parvoviruses may have different preferred forms of titration making comparative virology difficult even among related groups. Porcine parvovirus (PPV), canine parvovirus (CPV), and minute virus of mice (MVM) are usually titrated using different infectivity assays. A direct comparison of infectious virus titer between these parvoviruses was sought, and a tetrazolium salt assay, MTT has been applied to measure cytopathic effect produced by viral infection for different members of the parvovirus family. Infectious PPV measured using the MTT and the TCID50 assays exhibited excellent correlation and titers for CPV and MVM were consistently duplicated using the MTT assay. The MTT assay was also applied to an unrelated virus, Sindbis, which is routinely titrated by plaque assay. MTT titration of Sindbis virus mutants was found to be valuable for preliminary screening. This assay can be adapted, by correlation to an accepted titration method, to any viral system which produces measurable cytopathic effect.