Evaluation of cerebral perfusion deficit in stroke patients using new transcranial contrast imaging CPS technology--preliminary results.

BACKGROUND AND PURPOSE: Contrast-enhanced transcranial duplex sonography can be used to examine cerebral perfusion. This technique, however, is still faced with methodological problems. The aim of the present study is to evaluate cerebral perfusion deficit after administration of the contrast agent SonoVue in acute stroke patients using new contrast imaging software. METHODS: Ten subjects (6 male stroke patients and 4 healthy volunteers), were examined using transcranial duplex sonography (Acuson Sequoia 512 Ultrasound System) after a bolus injection of the contrast agent SonoVue. The transcranial examination was performed using transient response harmonic grey scale imaging with refill kinetics. The Sequoia ultrasonographic system was equipped with a new contrast harmonic imaging software "Cadence contrast pulse sequencing technology" (CPS). Triggered images with the mechanical index (MI) at 1.1 as well as continuous registration with MI at 0.28 were used for the evaluation of time intensity curves in several regions of interest. The sonographically imaged hypoperfused areas were compared with findings from MR imaging. RESULTS: In all healthy volunteers, the contrast-enhanced signal could be recognized well in the ipsi- and also in the contralateral hemisphere up to the skull crown. In stroke patients, the perfusion deficit in the area of the MCA could be detected ipsilaterally in all subjects using triggered registration. Additionally, the area of MCA infarction could also be visualized in two patients using contralateral insonation. The low MI continuous imaging was successful in three patients. For all patients, the ischaemic region corresponded well in shape and size with the findings from MR imaging. CONCLUSIONS: CPS enhances the possibility of perfusion-imaging in cerebral microcirculation and of perfusion-deficit-imaging in patients with cerebral ischaemia. Further studies with a larger number of patients should be carried out to improve this method.

Toxoplasma gondii in primary rat CNS cells: differential contribution of neurons, astrocytes, and microglial cells for the intracerebral development and stage differentiation.

The central nervous system (CNS) of the intermediate host plays a central role in the lifelong persistence of Toxoplasma gondii as well as in the pathogenesis of congenital toxoplasmosis and reactivated infection in immunocompromised patients. In order to analyze the parasite-host interaction within the CNS, the host cell invasion, the intracellular replication, and the stage conversion from tachyzoites to bradyzoites was investigated in mixed cultures of dissociated CNS cells from cortices of Wistar rat embryos. Two days post infection (p.i.) with T. gondii tachyzoites, intracellular parasites were detected within neurons, astrocytes, and microglial cells as assessed by double immunofluorescence and confocal microscopy. Quantitative analyses revealed that approximately 10% of neurons and astrocytes were infected with T. gondii, while 30% of the microglial cells harbored intracellular parasites. However, the replication of T. gondii within microglial cells was considerably diminished, since 93% of the parasitophorous vacuoles (PV) contained only one to two parasites which often appeared degenerated. This toxoplasmacidal activity was not abrogated after treatment with NO synthase inhibitors or neutralization of IFN-gamma production. In contrast, 30% of the PV in neurons and astrocytes harbored clearly proliferating parasites with at least four to eight parasites per vacuole. Four days p.i. with tachyzoites of T. gondii, bradyzoites were detected within neurons, astrocytes, and microglial cells of untreated cell cultures. However, the majority of bradyzoite-containing vacuoles were located in neurons. Spontaneous differentiation to the bradyzoite stage was not inhibited after addition of NO synthase inhibitors or neutralization of IFN-gamma. In conclusion, our results indicate that intracerebral replication of T. gondii as well as spontaneous conversion from the tachyzoite to the bradyzoite stage is sustained predominantly by neurons and astrocytes, whereas microglial cells may effectively inhibit parasitic growth within the CNS.

Influence of the dopamine D2 receptor (DRD2) genotype on neuroadaptive effects of alcohol and the clinical outcome of alcoholism.

The present study was performed to test the hypotheses that allelic variants at the human dopamine D2 receptor gene locus (DRD2) confer susceptibility to alcoholism or are associated with clinical subtypes of alcoholism. We investigated an A --> G substitution polymorphism in the 3'-untranslated region of exon 8 (E8) of DRD2 with allele frequencies of f(G) = 0.295 - 0.329. No significant association of the DRD2 genotype or allele frequencies with alcoholism was found in an association study including 283 alcoholics and 146 non-alcoholic controls. However, the frequent homozygous E8 A/A genotype with f(AA) = 0.47 - 0.48 was associated with increased anxiety and depression scores in alcoholics during the follow up after clinical detoxification treatment. In addition, E8 A/A was associated with increased suicide attempts and showed a tendency towards more severe withdrawal symptoms, early relapse and reduced responsiveness to the dopaminergic agonist apomorphine. Regression analysis revealed the DRD2 E8 genotype as the only significant factor determining withdrawal severity in female alcoholics. The findings suggest an influence of the DRD2 genotype on the neuropharmacological effects of chronic alcohol exposure and the clinical course of alcoholism.

Dopamine D2 receptor gene (DRD2) haplotypes in Caucasians.

The human dopamine D2 receptor gene (DRD2) is considered a candidate gene for neuro-psychiatric diseases. We typed three new DNA sequence variants in DRD2 intron 4, intron 6 and exon 8, in combination with the known TaqI A restriction fragment length polymorphism (RFLP) and exon 7 311Ser/Cys in 106 unrelated psychiatrically healthy Caucasians. Based on the genotypic data we delineated 10 distinct DRD2 haplotypes and their genetic relationship. Our data provide evidence that the Taq A1 allele and the 311Cys variant are components of different groups of haplotypes though both variants have been speculated to be associated with alcoholism or schizophrenia in recent studies. Therefore we conclude that the prior knowledge of the frequencies and genetic relationships of DRD2 haplotypes will lead to the selection of more suitable intragenic markers for future association studies.

No association of the structural dopamine D2 receptor (DRD2) variant 311Cys with alcoholism.

The human dopamine D2 receptor (DRD2) has been implied in the vulnerability for alcoholism and/or the modification of its severity. This is supported through animal experimental and pharmacological data. We analyzed the DRD2 311Ser/Cys polymorphism in 312 German alcoholics and 131 ethnically matched controls to investigate the association of genetic DRD2 variants with alcoholism or clinical characteristics of homogeneous subgroups of alcoholics. We observed no association between the 311Cys variant and alcoholism, and none of the clinical characteristics evaluated was significantly associated with 311Cys. The allele frequencies of the 311Cys variant were 0.026 and 0.031 in the alcoholics and controls, respectively. These are the highest reported 311Cys frequencies in Caucasians. The DRD2 TaqI A1/A2 restriction fragment length polymorphism was analyzed simultaneously in our samples. In most cases, the 311Cys allele is associated with the TaqI A2-allele. Data do not suggest a clinical relevance of the 311Cys variant in alcoholism. However, the relevance of this variant in other diseases or the existence of other DRD2 variants with altered receptor function or expression cannot be excluded.

The neuropathology and epidemiology of AIDS. A Berlin experience. A review of 200 cases.

The brains of 200 patients who died with Acquired Immunodeficiency Syndrome (AIDS) from Berlin were examined retrospectively. This study was specifically intended to evaluate and document the prevalence of neuropathologic abnormalities, establishing the frequency of the various types of structural lesions, their combinations, their relative incidence, and the risk factors involved in different age groups. The data were compared and contrasted with the findings reported from other parts of the world and other German cities. It was found that the mean age of this group of patients was 41.4 years old, 75% were homosexual/bisexuals (H/B) and 18.5% were drug abusers (DA). Only 5.5% were women. Brain parenchymal changes, called in this report, HIV-related encephalopathy (HIVRE), characterized by vacuolization or spongy changes and astrocytosis in the subcortical white matter, and occasionally in gray matter, were found in 67 patients (33.5%). Drug abusers had a higher incidence of HIVRE (59.5%) compared with homosexual/bisexuals (28%). This is statistically significant (p < 0.0005). CMV encephalitis was found in 26 patients (13%) (8% of the drug abusers in contrast to 13% in the homosexual/bisexuals group). Primary central nervous system lymphoma (PCNSL) was seen in 28 patients (14%) regardless of the risk factor involved. 20 (13%) of the 150 H/B and 3 (8%) of the 37 DA had CMV encephalitis. Of the 150 H/B, 24 (16%) had PCNSL compared with only 4 of 37 (11%) of the DA. A significant incidence of opportunistic infections, both protozoal and viral was found in all groups. Cerebral toxoplasmosis occurred in 68 patients (34%). Microglial (phagocytic) nodules, probably related to CMV or cerebral Toxoplasmosis, were observed in 40 cases (20%). Diffuse microglial proliferation was noted in 104 patients (52%). Cerebral cryptococcosis was found in three patients. Progressive multifocal leukoencephalopathy was seen in 16 patients (8%). Various combinations of CNS pathological processes were found in 44 of the patients (22%). These include concomitant infections with Toxoplasma gondii and HIVRE in 13 patients; Toxoplasmosis and PCNSL in 8 patients; Toxoplasmosis with CMV and HIVRE in 4 patients; Toxoplasmosis with CMV in 2 patients; Toxoplasmosis with PCNSL and CMV in 2 patients; Toxoplasmosis with PCNSL and HIVRE in 2 patients and Toxoplasmosis with PML and HIVRE in 2 patients; Cerebral CMV with PCNSL and HIVRE in 4 patients; Cerebral CMV with HIVRE in 2 patients; PML with PCNSL in one patient; PML with HIVRE in 2 patients; and PML with PCNSL and HIVRE in one patient. Cerebrovascular lesions were found in 34 patients (17%).(ABSTRACT TRUNCATED AT 400 WORDS)