Control of detrusor hyperreflexia by the intravesical instillation of oxybutynine hydrochloride

This report deals with the control of detrusor hyperreflexia by the intravesical instillation of oxybutynin hydrochloride (OH) in 10 male and 3 female patients with complete suprasacral spinal cord lesions having clean intermittent catheterisation (CIC) because of unbalanced voiding. The indication for intravesical OH application was persisting urinary incontinence despite CIC in 11 patients and in 2 patients detrusor hypercontractility. One 5 mg tablet of OH was dissolved in distilled water and the solution was instilled into the bladder through the catheter, which has been used for urodynamics and which was then removed. Six hours later cystometry was repeated and the clinical effects were studied especially with regard to continence/incontinence and side-effects. The differences in the cystometric bladder capacity and maximum detrusor pressure before and after instillation of OH are statistically highly significant. Clinically, from those 10 patients who were incontinent between CIC before, 9 remained dry during the 6-hour period. None of the patients reported any side-effect after intravesical application of OH. However, with subsequent oral medication 8 out of 12 patients complained of typical anticholinergic side-effects. These results indicate that treatment with topical OH is an effective alternative to treating detrusor hyperreflexia, especially in patients already on CIC because of unbalanced voiding, but with persisting urinary incontinence due to detrusor hyperreflexia. OH is well absorbed from the bladder, however absorption seems to be protracted compared to oral intake.     

Vaccination against hepatitis B in liver transplant recipients: pilot analysis of cellular immune response shows evidence of HBsAg-specific regulatory T cells.

After liver transplantation for hepatitis-B-related diseases, patients currently receive lifelong treatment with hepatitis B immunoglobulin to prevent endogenous reinfection with hepatitis B virus (HBV). Active immunization with hepatitis B vaccine would be a preferable alternative; however, most attempts to immunize these patients with standard vaccine have failed. A recent study with a new adjuvanted hepatitis B vaccine was exceptionally successful, leading to a high-titered long-lasting antibody response in 80% of all vaccinees. To identify the immunological mechanisms behind these unexpected results, the successfully vaccinated participants were tested for hepatitis B surface antigen (HBsAg)-specific T and B cells, and their cellular responses to revaccination with conventional vaccine were studied. HBsAg-specific CD4(+) T lymphocytes could be detected in 13 of 16 patients after immunization with the new vaccine. Unexpectedly, these T cells produced almost exclusively interleukin (IL)-10 and had a CD4(+)/CD25(+) phenotype. They were functionally active, suppressing cytokine secretion in HBsAg-specific (Th1) cells, thus representing antigen-specific regulatory T cells (T(Reg)). Following a booster dose with conventional vaccine 22-31 months after completion of the initial vaccination series, the T-cell pattern in the revaccinated individuals changed substantially: 7 days after revaccination 9 of 11 individuals showed a switch to a Th1-type immune response with HBsAg-specific T cells secreting IL-2, interferon gamma and tumor necrosis factor alpha as observed in healthy controls. Four weeks after the booster, 4 patients still showed a Th1-type cytokine pattern, whereas in 5 patients only IL-10-secreting cells were detectable. After 1 year, in 3 of 4 revaccinated individuals only IL-10-secreting cells could be found, whereas the specific T cells of the fourth patient still showed a Th1-type of response. HBsAg-specific T(Reg) cells could be demonstrated in HBV-positive liver transplant recipients successfully immunized with a new adjuvanted vaccine. Revaccination led to immediate disappearance of the these cells and the appearance of HBsAg-specific T cells with a Th1-type cytokine profile, which in most cases were replaced by the IL-10-secreting regulatory cells during the following months. The specific induction of T(Reg) cells could contribute to the poor response of liver transplant recipients to conventional vaccine. In conclusion,, for successful vaccination of these patients, a vaccine with a strong inhibitory effect on T(Reg) cells would be desirable.     

Sensitive and accurate quantitation of hepatitis B virus DNA using a kinetic fluorescence detection system (TaqMan PCR)

The laboratory diagnosis of hepatitis B virus (HBV) infection is based mainly on serological assays. Yet the detection and quantitation of viral DNA is necessary when addressing directly the question of infectivity or when monitoring the viral load during therapy. Standard hybridization assays allow for exact quantitation, but their sensitivity is limited to 10(5)-10(6) viral genomes per ml of serum. The most sensitive tests for HBV DNA are nested PCR systems, which recognize virtually one molecule of the target DNA per reaction. However, these assays only provide very coarse quantitative statements. To take advantage of both methods, a new assay for HBV DNA is described based on the commercial TaqMan system. This assay is capable of quantifying HBV DNA from the theoretical lower limit up to 10(10) genome equivalents per ml of serum and, thus, covers the complete range of naturally occurring states of infections. The method was calibrated on the basis of serial plasmid dilutions and compared with a well-established nested PCR system. More than 100 HBV positive sera and serial dilutions of the Eurohep standard for both ad and ay subtypes were analyzed. The assay reliably detected all HBV positive samples. It shows minimal run-to-run deviations, allows for quantitation that covers eight orders of magnitude, and finally, completely avoids the risk of cross-contamination by PCR products. Thus, this technique combines the sensitivity of PCR amplification and the quantitation potential of hybridization tests and it is time efficient and safer.     

TBE booster immunization according to the rapid immunization schedule: are 3-year booster intervals really necessary?

In order to evaluate the need for further booster immunizations, 222 subjects aged 20-52 years, who had received the first booster dose with a new tick-borne encephalitis (TBE) vaccine in a preceding study, were invited for a serological follow-up. A total of 191 and 182 adult subjects were analyzed for the persistence of neutralizing TBE antibodies at 1 and 2 years following the first booster immunization, respectively. Both serological follow-ups revealed high levels of neutralizing TBE antibodies in more than 99% of subjects. Although an expected decline of the respective geometric mean titers (GMTs) was noted after booster immunization, the titers were still far above the values noted after primary immunization at the 2-year follow-up. The kinetic curve clearly indicates a longer persistence of neutralizing TBE antibodies than currently expected. To conclude, these results suggest that the administration of a further booster dose 3 years after the first one (according to current recommendations) does not seem to be necessary in this study population.     

Outcome of an exercise to notify patients treated by a general surgeon infected with the hepatitis C virus.

BACKGROUND: Health-care workers infected with the hepatitis C virus (HCV) and performing exposure-prone procedures may expose their patients to the risk of nosocomial HCV infection. OBJECTIVE: To assess the number of provider-to-patient transmissions of HCV among former patients of an HCV-infected general surgeon. RESULTS: The notification exercise covered 1461 individuals, on whom the surgeon performed 1683 operations. Eighty-two percent of these patients were tested for markers of HCV infection, and all but six subjects turned out to be not infected with the virus. Two of the anti-HCV positive patients were already infected before their operations, one individual was not available for further molecular analyses, and three subjects harboured HCV isolates that belonged to a different subtype (i.e. 1b) than the variant detected in the surgeon's serum. CONCLUSION: In this retrospective survey, no provider-to-patient transmission of HCV was detected among 1192 former patients of an infected general surgeon. This finding, one more time, suggests that such nosocomial transmission events are probably very rare. Consequently, recommendations for the management and guidance of HCV-infected health-care workers should carefully balance the workers' rights against justified patients' interests.     

Delayed Humoral Immunity in a Patient with Severe Tick-borne Encephalitis after Complete Active Vaccination

Abstract Tick-borne encephalitis virus (TBEV) is a common cause of viral encephalitis in parts of Central and Eastern Europe. Active immunization results in a high rate of seroconversion and is the most effective measure of decreasing the incidence of tick-borne encephalitis (TBE). Currently, booster vaccinations are recommended every 3 years after completion of primary immunization. However, titers of neutralizing antibodies decline with time after vaccination and with age and thus may be insufficient to protect from disease in the elderly. We report on a 54-year-old patient who had received his last booster vaccination 3 years before developing a severe TBE with delayed induction and longterm persistence of anti-TBEV-IgM-antibodies.     

Safety and immunogenicity of concomitant vaccination with the cell-culture based Japanese Encephalitis vaccine IC51 and the hepatitis A vaccine HAVRIX1440 in healthy subjects: A single-blind,randomized, controlled Phase 3 study

In travellers often several pre-departure immunizations are indicated, thus data are needed about possible interactions between vaccines. This Phase 3 study investigated the immunogenicity and safety of IC51 (JE vaccine) and HAVRIX^®1440 (hepatitis A vaccine) when administered alone or concomitantly to healthy subjects. The immune response was compared between single and concomitant vaccination in terms of geometric mean titre (GMT) and seroconversion rate (SCR) on Days 28 and 56. Immunogenicity was comparable for the 2 vaccines whether given together or separately which suggests that travellers to such regions could receive the vaccinations concomitantly.     

Impact of maternal carrier status on immunologic markers for protection after hepatitis B vaccination in infancy: A meta-analysis

Better protection against hepatitis B infection in offspring of carrier mothers has been postulated because of a booster effect by close maternal contact. Empirical evidence, however, is inconclusive. Immunologic markers for protection against hepatitis B are anti-HBs≥10mIU/ml or response to booster in case anti-HBs had fallen below 10mIU/ml. The objective of this paper was to asses whether immunologic markers suggest a higher protection after hepatitis B vaccination in offspring of carrier mothers. A systematic review was performed in order to identify all studies in offspring of carrier and non-carrier mothers reporting the proportions of individuals with anti-HBs≥10mIU/ml after infant hepatitis B vaccination with a presently recommended dose in children aged 5years or older or response to a booster dose in case anti-HBs was below 10mIU/ml. Associations between carrier status and the proportions of anti-HBs≥10mIU/ml or booster response were analysed by random effects models with adjustment for age and potential confounders. We identified 19 studies providing proportions of anti-HBs≥10mIU/ml with explicit information regarding the maternal carrier status. These studies reported 3245 children of carrier mothers aged up to 20years and 4602 children of non-carrier mothers aged up to 14years. Antibody titres≥10mIU/ml were detected in 75.8% of children of carrier and 63.6% of non-carrier mothers. A random effects model with adjustment for confounding yielded an odds ratio of 2.43 (95% CI 1.24-4.75) suggesting a markedly higher probability of anti-HBs≥10mIU/ml in offspring of carrier compared to non-carrier mothers. The distribution of proportions of individuals with post booster increase of anti-HBs titres≥10mIU/ml stratified by age at booster (≤10years and >10years) showed no differences between offspring of carrier and non carrier mothers up to the age of 10years and only marginal differences thereafter. In conclusion the proportions of anti-HBs≥10mIU/ml were clearly higher in offspring of carrier mothers years after infant vaccination but there appeared to be no clinically relevant difference in response to booster. It is unclear to which extent higher proportions of breakthrough infections contribute to the higher proportions of protective antibody titres in offspring of carrier mothers.