A non-living nasal influenza vaccine can induce major humoral and cellular immune responses in humans without the need for adjuvants

Twenty-eight healthy adult volunteers were immunized intranasally with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1), either in saline or mixed with formaldehyde-inactivated Bordetella pertussis as a mucosal adjuvant, or in a thixotropic vehicle with mucoadhesive properties. After four doses, all groups of vaccinees developed significant IgG- and IgA-antibody responses, measured by ELISA, in respectively serum and nasal secretions. None of the volunteers had demonstrable hemagglutination inhibition (HAI) antibodies in serum before being immunized, whereas more than 80% of them reached HAI titers>or=40, considered protective, after immunizations. In addition, cellular immune responses, measured as significant increases in CD4+ T-cell proliferation and granzyme B-producing cytotoxic T-cells, were detected against the vaccine strain as well as against heterologous virus strains (H3N2). However, no additive effect on these responses could be demonstrated with use of B. pertussis or the thixotropic substance in the present vaccines. It appeared, actually, that the mucoadhesive vehicle containing the thixotropic substance was less efficient than were the two other formulations. An influenza vaccine made as a simple particulate formulation of inactivated virus, and given repeatedly onto the nasal mucosa, may thus be an attractive alternative to currently available vaccines.     

Alterations in T-Cell Subset Frequency in Peripheral Blood in Obesity

Background: Obesity affects the regulation of immune and inflammatory responses. This study characterizes differences in peripheral blood lymphocyte phenotype in obese humans. Methods: Frequencies of lymphocyte subsets among peripheral blood mononuclear cells were compared between 10 obese (BMI ≥35) and 10 lean subjects, as determined by antibodies directed against cluster differentiation (CD) markers. Results: Obese patients demonstrated an increased frequency of CD3+CD4+ T-cells (mean difference 12%, P=0.004), a decreased frequency of CD3+CD8+ T-cells (mean difference 9.4%, P=0.016) and an increased frequency of CD3+CD8+CD95+ T-cells (mean difference 13.3%, P=0.032). No other differences among T-cell or monocyte subsets were noted. Conclusions: Obesity is associated with alterations in frequencies of peripheral CD4+ and CD8+ T-cells and aberrations in the expression of CD95 among CD8+ T-cells. These data suggest both CD4+ and CD8+ T-cell compartments, as well as the regulation of CD95 expression on CD8+ T-cells, as targets for further study into obesity's effects on the immune system.     

Emotional responses during unilateral amobarbital anesthesia: differential hemispheric contributions?

OBJECTIVES: To explore (1) effects of test and subject variables in determining euphoric and dysphoric responses during unilateral amobarbital anesthesia and (2) which cerebral areas contribute to the emotional responses. METHOD: Incidence of euphoric and dysphoric reactions during left- and right-sided amobarbital anesthesia of the internal carotid artery (ICA) and selective anesthesia of the middle cerebral (MCA) and the posterior cerebral (PCA) artery was recorded. The sample comprised 270 Norwegians (6-61 years), and a total of 562 injections were performed under conditions endeavoring to calm down the patients. RESULTS: The overall incidence of observed emotional responses during ICA anesthesia was 21.5%, euphoric reactions being about 10 times more frequent than dysphoric. The incidence of euphoric reactions, however, was not significantly higher under right- than under left-sided anesthesia, and dysphoric reactions were not more frequent under left- than under right-sided anesthesia. Indeed, 13 patients showed elevated mood under both right- and left-sided anesthesia. Anesthesia of the territories of ICA and MCA gave rise to similar results, while no cases of mood change were observed under selective PCA anesthesia. CONCLUSION: It is concluded that unilateral amobarbital anesthesia as such, irrespective of side, may trigger both euphoric and dysphoric responses. The relative frequency obtained is influenced importantly both by the emotional responsiveness of the subjects and the emotional climate of the test situation. Finally, it is suggested that brain regions supplied by the PCA contribute less to modulation of euphoric and dysphoric responses than those supplied by the MCA or the ICA.     

Genotoxicity and toxicity of the potential cancer-preventive agent polyphenon E

The potential health benefits of green tea continue to attract public and scientific interests and are attributed in part to polyphenolic catechin constituents. Polyphenon E (Poly E) is a decaffeinated green tea catechin mixture containing about 50% epigallocatechin gallate and 30% other catechins. We evaluated the toxicity and genotoxicity of Poly E by using two in vitro assays: bacterial mutagenesis in a Salmonella typhimurium-E. coli assay and the L5178Y mouse lymphoma cell thymidine kinase (Tk) gene mutation assay. In addition, we used two in vivo genotoxicity assays: the mouse micronucleus assay and the Big Blue cII transgenic mouse mutation assay. Repeat-dose toxicity evaluations were performed in mice in parallel with the Big Blue transgenic mutation assays. No significant increases in the revertant colonies were found in the bacterial mutagenesis assay, but a significant increase in the mutant frequency (MF) at the Tk locus was observed in the mouse lymphoma test system. We observed toxicity in mice when Poly E was administered at doses of 2,000 mg/kg/day. Lower doses produced no significant increases in micronucleated erythrocytes in the bone marrow of Swiss-Webster mice and no significant increases in cII transgene MF in the liver, lung, or spleen compared with controls. These results indicate that Poly E, although toxic at high doses (2,000 mg/kg/day), poses minimal genotoxic concern. In addition, these studies highlight the importance of using both in vitro and in vivo systems in genetic toxicity screening of pharmaceuticals before they are administered to humans.     

Relation of occupational exposure to respiratory symptoms and asthma in a general population sample: self-reported versus interview-based exposure data

The objective of this study was to examine how the consistency of self-reported exposure to dust or gas, asbestos, and quartz varied between subjects with and those without respiratory symptoms and asthma in a Norwegian community sample () in 1987-1988. Exposure characterization obtained in a structured work history interview was used as the "gold standard." The authors also wanted to assess how the exposure-disease relation differed when the exposure was based on self-reported versus interview-obtained data. The prevalence of self-reported exposure to dust or gas, asbestos, and quartz was 28%, 5%, and 4%, respectively. The sensitivity of the self-reported exposure data varied from 21% to 64% and was higher in those with than in those without the respiratory disorders. The specificity varied from 78% to 100% and was lower in those with than in those without the respiratory disorders. The sex-, age-, and smoking-adjusted odds ratios of the respiratory disorders in those with exposure to dust or gas and to asbestos were only slightly reduced when misclassification was taken into account. The corresponding numbers for exposure to quartz were halved and lost their statistical significance when the misclassification was allowed for. In this general population sample, the self-reported occupational, airborne exposure data were differentially misclassified by disease status.     

Reconstructive urology in the nordic countries--a hospital questionnaire survey

A hospital survey of adult reconstructive urologic surgery in the Nordic countries is presented. The response rate was 80% and included most general hospitals and university clinics. Despite similarities between the healthcare systems of the various countries several differences were found. Cystectomy was performed in a large number of institutions in all countries except Denmark. The annual number of orthotopic bladder substitutions per institution was calculated as three to four (range of medians for each country) and the number of continent cutaneous diversions as two to seven. Open urethral procedures were performed more frequently in Sweden than in the other countries. Surgery for penile curvature and implantation of three-component prostheses for erectile dysfunction was more commonly performed in Denmark and Iceland compared to Sweden.