Comparative immunogenicity of a PreS/S hepatitis B vaccine in non- and low responders to conventional vaccine

Conventional hepatitis B vaccines do not elicit adequate antibody production in 5-10% vaccinees. This trial tests the ability of a third-generation vaccine, containing PreS1 and PreS2 antigens in addition to the S antigen, to elicit seroprotective titres in documented non- and low-responders, compared with those to a conventional vaccine. In the primary population of non-responders (<10 IU/l anti-HBs antibodies after > or = 4 previous injections of conventional vaccine) an enhanced antibody response was seen to additional injections of the third-generation vaccine compared with a conventional vaccine (absolute difference 14.9%; P = 0.006). Enhanced antibody responses were also found in a population that included low responders.

The multicenter trial SAKK 37/95 of cladribine, cyclophosphamide and prednisone in the treatment of chronic lymphocytic leukemias and low-grade non-Hodgkin's lymphomas

A multicenter trial was performed to confirm the therapeutic efficacy and the toxicity profile of the combination of cladribine, cyclophosphamide and prednisone in low-grade non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Twenty-three adults with previously treated (61%) or untreated (39%) NHL International Working Formulation A or Binet B and C CLL were administered cladribine 0.1 mg/kg/day as a subcutaneous bolus for 5 days, intravenous cyclophosphamide 500 mg/m2 on day 1, and oral prednisone 40 mg/m2 on days 1-5, every 4 weeks. Unexpected early hematological toxicities led to dose modifications for pretreated patients who received cladribine for 3 days only up to a maximum of five courses. Responses were observed in 75%, with 7 patients obtaining a complete clinical and hematological response. Median duration of complete response was 9 months. Median time to progression or relapse was 31 months. Myelosuppression and infections were dose limiting whereas posttreatment complications, including fatalities, resulted from infections. Median overall survival time from trial entry was 60 months. Activity of the combination of cladribine, cyclophosphamide and prednisone was confirmed. However, in the specific setting of a multicenter trial, unexpected fatal infectious episodes occurred in pretreated patients. Great caution is thus required in these susceptible patients and the routine use of corticosteroids should probably be abandoned.

Clinical evaluation of root filled teeth restored with or without post-and-core systems in a specialist practice setting

AIM: To assess survival rates and complications of root-filled teeth restored with or without post-and-core systems over a mean observation period of >or=4 years. METHODOLOGY: A total of 325 single- and multirooted teeth in 183 subjects treated in a private practice were root filled and restored with either a cast post-and-core or with a prefabricated titanium post and composite core. Root-filled teeth without post-retained restorations served as controls. The restored teeth served as abutments for single unit metal-ceramic or composite crowns or fixed bridges. Teeth supporting cantilever bridges, overdentures or telescopic crowns were excluded. RESULTS: Seventeen teeth in 17 subjects were lost to follow-up (17/325: 5.2%). The mean observation period was 5.2 +/- 1.8 (SD) years for restorations with titanium posts, 6.2 +/- 2.0 (SD) years for cast post-and-cores and 4.4 +/- 1.7 (SD) years for teeth without posts. Overall, 54% of build-ups included the incorporation of a titanium post and 26.5% the cementation of a cast post-and-core. The remaining 19.5% of the teeth were restored without intraradicular retention. The adjusted 5-year tooth survival rate amounted to 92.5% for teeth restored with titanium posts, to 97.1% for teeth restored with cast post-and-cores and to 94.3% for teeth without post restorations, respectively. The most frequent complications included root fracture (6.2%), recurrent caries (1.9%), post-treatment periradicular disease (1.6%) and loss of retention (1.3%). CONCLUSION: Provided that high-quality root canal treatment and restorative protocols are implemented, high survival and low complication rates of single- and multirooted root-filled teeth used as abutments for fixed restorations can be expected after a mean observation period of >or=4 years.

Validity and clinical significance of biomechanical testing of implant/bone interface

Purpose: The aim of this paper was to review the clinical literature on the Resonance frequency analysis (RFA) and Periotest techniques in order to assess the validity and prognostic value of each technique to detect implants at risk for failure. Material and methods: A search was made using the PubMed database to find clinical studies using the RFA and/or Periotest techniques. Results: A limited number of clinical reports were found. No randomized-controlled clinical trials or prospective cohort studies could be found for validity testing of the techniques. Consequently, only a narrative review was prepared to cover general aspects of the techniques, factors influencing measurements and the clinical relevance of the techniques. Conclusions: Factors such as bone density, upper or lower jaw, abutment length and supracrestal implant length seem to influence both RFA and Periotest measurements. Data suggest that high RFA and low Periotest values indicate successfully integrated implants and that low/decreasing RFA and high/increasing Periotest values may be signs of ongoing disintegration and/or marginal bone loss. However, single readings using any of the techniques are of limited clinical value. The prognostic value of the RFA and Periotest techniques in predicting loss of implant stability has yet to be established in prospective clinical studies. To cite this article: Aparicio C, Lang N P, Rangert B. Validity and clinical significance of biomechanical testing of implant/bone interface. Clin. Oral Imp. Res., 17 (Suppl. 2), 2006; 2-7.

Cerebral connectivity and psychotic personality traits : A diffusion tensor imaging study

This study aims to investigate the relationship between regional connectivity in the brain white matter and the presence of psychotic personality traits, in healthy subjects with psychotic traits. Thirteen healthy controls were administered the MMPI-2, to assess psychotic traits and, according to MMPI results, a dichotomization into a group of "high-psychotic" and "low-psychotic" was performed. Diffusion tensor imaging (DTI) was used as a non-invasive measure, in order to obtain information about the fractional anisotropy (FA), an intravoxel index of local connectivity and, by means of a voxelwise approach, the between-group differences of the FA values were calculated. The "high-psychotic" group showed higher FA in the left arcuate fasciculus. Subjects with low scores for psychotic traits had significantly higher FA in the corpus callosum, right arcuate fasciculus, and fronto-parietal fibers. In line with previous brain imaging studies of schizophrenia spectrum disorders, our results suggest that psychotic personality traits are related to altered connectivity and brain asymmetry.

[The model project "newborn auditory screening" in the Upper Palatinate: high process and result quality of an interdisciplinary concept]

BACKGROUND: In May 2003, a newborn auditory screening program was initiated in the Upper Palatinate. METHODS: Sequential OAE- and BERA-screening was conducted in all hospitals with obstetric facilities. The Screening Center at the Public Health Authority was responsible for the coordination of the screening process, completeness of participation, the follow-up of all subjects with a positive screening test and the quality of instrumental screening. RESULTS: A total of 96% of 17,469 newborns were screened. The referral rate at discharge was 1.6% (0.4% for bilateral positive findings). For 97% of the positive screening results, a definite diagnosis to confirm or exclude hearing loss was achieved; for 43% only after intervention by the Screening Center. Fifteen children with profound bilateral hearing impairment were identified of whom eight were only detected by the intervention of the Screening Center. CONCLUSION: The effective structures established in the Upper Palatinate provide a standard for the quality of neonatal auditory screening achievable in Germany.

High variability and non-neutral evolution of the mammalian avpr1a gene

BACKGROUND: The arginine-vasopressin 1a receptor has been identified as a key determinant for social behaviour in Microtus voles, humans and other mammals. Nevertheless, the genetic bases of complex phenotypic traits like differences in social and mating behaviour among species and individuals remain largely unknown. Contrary to previous studies focusing on differences in the promotor region of the gene, we investigate here the level of functional variation in the coding region (exon 1) of this locus. RESULTS: We detected high sequence diversity between higher mammalian taxa as well as between species of the genus Microtus. This includes length variation and radical amino acid changes, as well as the presence of distinct protein variants within individuals. Additionally, negative selection prevails on most parts of the first exon of the arginine-vasopressin receptor 1a (avpr1a) gene but it contains regions with higher rates of change that harbour positively selected sites. Synonymous and non-synonymous substitution rates in the avpr1a gene are not exceptional compared to other genes, but they exceed those found in related hormone receptors with similar functions. DISCUSSION: These results stress the importance of considering variation in the coding sequence of avpr1a in regards to associations with life history traits (e.g. social behaviour, mating system, habitat requirements) of voles, other mammals and humans in particular.

Patent foramen ovale and ventricular septal defect closure

Despite the growing recognition of the patent foramen ovale (PFO), particularly when associated with an atrial septal aneurysm, as risk factor for several disease manifestations (above all paradoxical embolism), the optimal treatment strategy for symptomatic patients remains controversial. Percutaneous PFO closure is a minimally invasive procedure which can be performed with high success and low morbidity. For secondary prevention of recurrent embolic events, it appears to be clinically at least as effective as oral anticoagulation. Ventricular septal defects (VSDs) are the most common congenital heart defects. Percutaneous VSD closure is more intricate than PFO closure. It is associated with a significant risk of both peri-interventional and mid-term complications. In suitable patients with congenital VSD, device closure may well be the preferred treatment both for muscular or perimembranous VSDs and for residual defects after surgical VSD closure. The risk of complete atrioventricular conduction block remains a concern in the perimembranous group. The history, technique and clinical role of percutaneous PFO and VSD closure are discussed, with emphasis on current problems and future developments.

Hemispheric lateralization patterns and psychotic experiences in healthy subjects

The hypothesis that psychotic experiences in healthy subjects are associated with a dysfunction of the right hemisphere is supported by some, but not all, available studies. Differences in gender composition of study samples may explain in part the divergent findings. The present study was carried out in 42 healthy, right-handed university students. Scores on the Schizophrenia and Paranoia scales of the Minnesota Multidimensional Personality Inventory-2 were used in correlation analyses and to define a High- and a Low-Psychotic group. Brain Electrical Microstates and Low Resolution Electromagnetic Tomography (LORETA) source analyses of the auditory P300 (P3a and P3b) components of the event-related potential, as well as a battery of neuropsychological tests, were used to assess hemispheric functioning. Scores on the Paranoia scale were positively associated with a leftward shift of the P3a topographic descriptors in females but not in males. When comparing High-Psychotic and Low-Psychotic females, a leftward shift of P3a descriptors and an increased cortical activation in left fronto-temporal areas were observed in the High-Psychotic group. Our results demonstrated gender-related differences in the pattern of hemispheric imbalance associated with psychotic experiences in healthy subjects.

Expression, purification and low-resolution structure of human vitamin C transporter SVCT1 (SLC23A1)

Expression and purification of human membrane proteins for structural studies represent a great challenge. This is because micro- to milligram amounts of pure isolated protein are required. To this aim, we successfully expressed the human vitamin C transporter-1 (hSVCT1; SLC23A1) in Xenopus laevis oocytes and isolated highly pure protein in microgram amounts. Recombinant hSVCT1 was functional when expressed in oocytes and glycosylated. Structural analysis of purified hSVCT1 by transmission electron microscopy and single particle analysis unveiled its shape, dimensions and low-resolution structure as well as the existence of a major monomeric and minor dimeric population. Chemical crosslinking of isolated oocyte membranes containing expressed hSVCT1 indicated similar oligomeric states of hSVCT1 in lipid bilayers. This work reports the first purification and structural analysis of a human SVCT protein and opens the way for future functional and structural studies using purified hSVCT1.

Metabolic adaptations and changes of the mammary immune response during beta-hydroxybutyrate administration

Elevation of ketone bodies occurs frequently after parturition during negative energy balance in high yielding dairy cows. Previous studies illustrated that hyperketonemia interferes with metabolism and it is assumed that it impairs the immune response. However, a causative effect of ketone bodies could not be shown in vivo before, because spontaneous hyperketonemia comes usually along with high NEFA and low glucose concentrations. The objective was to study effects of beta-hydroxybutyrate (BHBA) infusion and an additional intramammary lipopolysaccharide (LPS) challenge on metabolism and immune response in dairy cows. Thirteen dairy cows received intravenously either a BHBA infusion (group BHBA, n=5) to induce hyperketonemia (1.7 mmol/L), or an infusion with a 0.9 % saline solution (Control, n=8) for 56 h. Infusions started at 0900 on day 1 and continue up to 1700 two days later. Two udder quarters were challenged with 200 μg Escherichia coli-LPS 48 h after the start of infusion. Blood samples were taken one week and 2 h before the start of infusions as reference samples and hourly during the infusion. Liver and mammary gland biopsies were taken one week before the start of the infusion, 48 h after the start of the infusion, and mammary tissues was additionally taken 8 h after LPS challenge (56 h after the start of infusions). Rectal temperature (RT) and somatic cell count (SCC) was measured before and 48 h after the start of infusions and hourly during LPS challenge. Blood samples were analyzed for plasma glucose, BHBA, NEFA, triglyceride, urea, insulin, glucagon, and cortisol concentration. The mRNA abundance of factors related to potential adaptations of metabolism and immune system was measured in liver and mammary tissue biopsies. Differences between blood constituents, RT, SCC, and mRNA abundance before and 48 h after the start of infusions, and differences between mRNA abundance before and after LPS challenges were tested for significance by GLM of SAS procedure with treatment as fixed effect. Area under the curve was calculated for blood variables during 48 h BHBA infusion and during the LPS challenge, and additionally for RT and SCC during the LPS challenge. Most surprisingly, both plasma glucose and glucagon concentration decreased during the 48 h of BHBA infusion (P<0.05). During the 48 h of BHBA infusion, serum amyloid A mRNA abundance in mammary gland was increased (P<0.01), and haptoglobin (Hp) mRNA abundance tended to increase in cows treated with BHBA compared to control group (P= 0.07). RT, SCC, and candidate genes related to immune response in the liver were not affected by BHBA infusion. However, during LPS challenge the expected increase of both plasma glucose and glucagon concentration was much less pronounced in the animals treated with BHBA (P<0.05) and also SCC increased much less pronounced in the animals infused with BHBA (P<0.05) than in the controls. An increased BHBA infusion rate to maintain plasma BHBA constant could not fully compensate for the decreased plasma BHBA during the LPS challenge which indicates that BHBA is used as an energy source during the immune response. In addition, BHBA infused animals showed a more pronounced increase of mRNA abundance of IL-8, IL-10, and citrate synthase in the mammary tissue of LPS challenged quarters (P<0.05) than control animals. Results demonstrate that infusion of BHBA affects metabolism through decreased plasma glucose concentration which is likely related to a decreased release of glucagon during hyperketonemia and during additional inflammation. It also affects the systemic and mammary immune response which may reflect the increased susceptibility for mastitis during spontaneous hyperketonemia. The obviously reduced gluconeogenesis in response to BHBA infusion may be a mechanism to stimulated the use of BHBA as an energy source instead of glucose, and/or to save oxaloacetate for the citric acid cycle instead of gluconeogenesis and as a consequence to reduce ketogenesis.