Gilbert's syndrome and hyperbilirubinaemia in ABO-incompatible neonates

We asked whether UDP glucuronosyltransferase (UGT) gene promoter polymorphism (Gilbert's syndrome) would increase hyperbilirubinaemia in direct Coombs' negative ABO-incompatible neonates, as seen in other combinations with this condition. 40 ABO-incompatible and 344 ABO-compatible controls had an allele frequency of 0.35 for the variant promoter gene. The incidence of hyperbilirubinaemia was significantly higher only in the former who were also homozygotes for the variant UGT promoter, compared with ABO-incompatible babies homozygous for the normal UGT promoter (43% vs 0, p=0.02), and with ABO-compatible controls of all UGT genotypes combined (relative risk 5.65, 95% CI 2.23-14.31). Gilbert's syndrome is a determining factor for neonatal hyperbilirubinaemia ABO incompatibility.     

Knowledge and attitudes about microsatellite instability testing among high-risk individuals diagnosed with colorectal cancer.

For individuals meeting Bethesda criteria for hereditary nonpolyposis colorectal cancer syndrome, the microsatellite instability (MSI) test is recommended as a screening evaluation before proceeding to genetic testing. The MSI test is new to the medical setting, but will be increasingly used to screen patients at high risk for hereditary nonpolyposis colorectal cancer. The main goals of this study were to examine knowledge about and exposure to the MSI test among individuals considering the test, to evaluate perceived benefits and barriers to undergoing the MSI test, and to identify the demographic, medical, and psychosocial correlates of the perceived benefits and barriers to undergoing the test. One hundred and twenty-five patients completed a survey after being offered the test, but prior to making the decision whether to pursue MSI testing. Results indicated low levels of knowledge about and previous exposure to the MSI test. Participants held positive attitudes about the potential benefits of the test and perceived few barriers to undergoing the test. Motivations were similar to those cited by individuals considering other genetic tests. Participants with nonmetastatic disease, with lower perceived risk for cancer recurrence, and who reported more self-efficacy endorsed more benefits from the test. Higher levels of cancer-specific psychological distress were associated with more perceived barriers to having the test. These findings suggest that individuals considering the MSI test know very little about it but hold positive attitudes about the test's utility. More distressed patients, patients who perceive themselves at higher risk for cancer recurrence, and patients with metastatic disease might be less motivated to have the MSI test.     

Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines.

BACKGROUND: Treatment-related neurotoxicity has been recognized as a significant problem in patients with primary central nervous system lymphoma (PCNSL) as effective treatment has increased survival rates. There is, however, a paucity of research on cognitive functions in this population. DESIGN: In a review of the literature, a total of 17 articles that described cognitive outcome in adult PCNSL patients were identified. RESULTS: The studies that assessed cognitive functions after whole-brain radiotherapy combined with chemotherapy reported cognitive impairment in most patients. Patients treated with chemotherapy alone had either stable or improved cognitive performance in most studies. Methodological problems, however, limited the ability to ascertain the specific contribution of disease and various treatment interventions to cognitive outcome. On the basis of the literature review, a battery of cognitive and quality-of-life (QoL) measures to be used in prospective clinical trials was proposed. The battery is composed of five standardized neuropsychological tests, covering four domains sensitive to disease and treatment effects (attention, executive functions, memory, psychomotor speed), and QoL questionnaires, and meets criteria for use in collaborative trials. CONCLUSION: The incorporation of formal and systematic cognitive evaluations in PCNSL studies will improve our understanding of treatment-related neurotoxicity in this population.     

Transplantation of bone marrow-derived mesenchymal stem cells rescue photoreceptor cells in the dystrophic retina of the rhodopsin knockout mouse

Background Retinitis pigmentosa belongs to a large group of degenerative diseases of the retina with a hereditary background. It involves loss of retinal photoreceptor cells and consequently peripheral vision. At present there are no satisfactory therapeutic options for this disease. Just recently the use of mesenchymal stem cells has been discussed as one therapeutical option for retinal degeneration, as they have been shown to differentiate into various cell types, including photoreceptor cells. In this article we wanted to investigate the potency of mesenchymal stem cells to induce rescue effects in an animal model for retinitis pigmentosa, the rhodopsin knockout mouse. Methods For the experiments, three experimental groups of 10 animals each were formed. The first group consisted of untreated rhodopsin knockout (rho^-/-) animals used as controls. The second group consisted of rho^-/- mice that had received an injection of mouse mesenchymal stem cells, which were transduced using an adenoviral vector containing the sequence for the green fluorescent protein (GFP) prior to transplantation. In the third sham group, animals received an injection of medium only. Thirty-five days after transplantation, GFP-expressing cells were detected in whole-mount preparations of the retinas as well as in cryostat sections. For the detection of rescue effects, semi-thin sections of eyes derived from all experimental groups were produced. Furthermore, rescue effects were also analysed ultrastructurally in ultrathin sections. Results Histological analysis revealed that after transplantation, cells morphologically integrated not only into the retinal pigment epithelium but also into layers of the neuroretina displaying neuronal and glial morphologies. Furthermore, significant rescue effects, as demonstrated by the occurrence of preserved photoreceptor cells, were detected. Conclusions Our data indicate that mesenchymal stem cells can prolong photoreceptor survival in the rhodopsin knockout mouse, also providing evidence of a therapeutical benefit in retinitis pigmentosa. This work was funded by “Pro Retina”.     

AIDS AS A CHALLENGE FOR THE DEVELOPMENT OF THE TREATMENT OF OPIOID DEPENDENTS IN CHINA Report on the 9th National Conference on Drug Dependence, MMT and HIV Prevention in Sanya/Hainan (VR China), 1-5 November 2006

Nearly 100 experts from all over China attended the Chinese National Conference on Drug Dependence in Sanya/Hainan. The participants came from drug abuse treatment centers, methadone clinics and drug research institutes. The conference's focus was on the question how drug abuse treatment shall and might be part of HIV prevention. CHINALi xiao(The Federal Drug Commissioner with the Federal Ministry of Health, Berlin)     

A longitudinal study of autoantibodies against central nervous system tissue and gangliosides in connective tissue diseases

Our objective was to investigate longitudinally, antibodies against central nervous tissue (anti-CNS) derived from bovine brain and gangliosides GM 1, GD1a, GD1b, and GT1b in 91 patients with connective tissue diseases (systemic lupus erythematosus, n = 38; mixed connective tissue disease, n = 16; primary Sjogren's syndrome, n = 7; progressive systemic sclerosis, n= 13; polymyositis/dermatomyositis, n=4; overlap syndrome, n = 5; undifferentiated connective tissue disease, n = 8). Anti-CNS and anti-ganglioside antibodies, measured by enzyme-linked immunosorbent assay, were found in 73% and 63% of patients, respectively. Anti-CNS positive sera were also reactive in Western blotting in 74% of cases and recognized up to 14 different polypeptides from 29 to 130 kDa. Anti-CNS and anti-ganglioside antibodies reflected only in a limited extent the disease activity. In 27 of 58 patients, anti-CNS antibodies remained positive independently of disease activity and antibody levels did not correlate with the phases of exacerbations. A total of 36 of 60 anti-CNS-positive patients, in contrast to two of 22 anti-CNS-negative patients, had major neuropsychiatric manifestations (P < 0.001). Anti-ganglioside antibodies were not significantly associated with neuropsychiatric manifestations. In conclusion, our longitudinal data suggest that anti-CNS antibodies may be an important marker for the diagnosis of cerebral involvement in connective tissue diseases, but the pathogenic role of these autoantibodies remains to be determined.     

Pattern of serum autoantibodies allows accurate distinction between a tumor and pathologies of the same organ

PURPOSE: Recent studies impressively showed the diagnostic potential of seroreactivity patterns for different tumor types, offering the prospect for low-cost screening of numerous tumor types simultaneously. One of the major challenges toward this goal is to prove that seroreactivity profiles do not only allow for identifying a tumor but also allow for distinguishing tumors from other pathologies of the same organ. EXPERIMENTAL DESIGN: We chose glioma as a model system and tested 325 sera (88 glioma, 95 intracranial tumors, 60 other brain pathologies, and 82 healthy controls) for seroreactivity on a panel of 35 antigens. RESULTS: We were able to discriminate between glioma and all other sera with cross-validated specificity of 86.1%, sensitivity of 85.2%, and accuracy of 85.8%. We obtained comparably good results for the separation of glioma versus nontumor brain pathologies and glioma versus other intracranial tumors. CONCLUSION: Our study provides first evidence that seroreactivity patterns allow for an accurate discrimination between a tumor and pathologies of the same organ even between different tumor types of the same organ.     

Probable adult polyglucosan body disease

Adult polyglucosan body disease is a clinicopathologic entity characterized by progressive upper and lower motor neuron dysfunction, sensory loss in the lower extremities, sphincter dysfunction, and occasionally dementia. Pathologically, numerous large polyglucosan bodies are noted in peripheral nerves, cerebral hemispheres, and the spinal cord, as well as in other systemic tissues. We present a case of probable adult polyglucosan body disease based on clinical history and examination, magnetic resonance images, and sural nerve biopsy findings.