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Biomedical subjects

Gabriele Arendt

Publications and source records attributed to Gabriele Arendt.

At least 19 recordsLinked to original sources
PubMed2007

CD8 T-cell subsets and viral load in the cerebrospinal fluid of therapy-naive HIV-infected individuals.

Central nervous system involvement is common in HIV infection. We determined the relationship between T-cell subsets and viral load in the cerebrospinal fluid (CSF) of therapy-naive, asymptomatic HIV-infected individuals. A shift from naive to effector-memory CD8 T cells was observed in the CSF of HIV-infected individuals compared with controls. The HIV load strongly correlated with CD8 T cells in CSF. Effector-memory CD8 T cells were positively and effector CD8 T cells were negatively associated with viral replication in CSF.

CD8-Positive T-Lymphocytes↗
PubMed2006

Altered CD4+/CD8+ T-cell ratios in cerebrospinal fluid of natalizumab-treated patients with multiple sclerosis.

BACKGROUND: Treatment with natalizumab, a monoclonal antibody against the adhesion molecule very late activation antigen 4, an alpha4beta(1) integrin, was recently associated with the development of progressive multifocal leukoencephalopathy, a demyelinating disorder of the central nervous system caused by JC virus infection. OBJECTIVE: To test the effect of natalizumab treatment on the CD4(+)/CD8(+) T-cell ratios in cerebrospinal fluid (CSF) and peripheral blood. DESIGN: Prospective longitudinal study. SETTING: Academic and private multiple sclerosis centers. PATIENTS: Patients with multiple sclerosis (MS) treated with natalizumab, untreated patients with MS, patients with other neurologic diseases, and human immunodeficiency virus-infected patients. MAIN OUTCOME MEASURES: CD4(+) and CD8(+) T cells were enumerated in CSF and peripheral blood. The mean fluorescence intensity of unbound alpha4 integrin on peripheral blood CD4(+) and CD8(+) T cells was analyzed before and after natalizumab therapy. RESULTS: Natalizumab therapy decreased the CSF CD4(+)/CD8(+) ratio of patients with MS to levels similar to those of human immunodeficiency virus-infected patients. CD4(+)/CD8(+) ratios in peripheral blood in patients with MS progressively decreased with the number of natalizumab doses, but they remained within normal limits. Six months after the cessation of natalizumab therapy, CSF CD4(+)/CD8(+) ratios normalized. The expression of unbound alpha4 integrin on peripheral blood T cells decreases with natalizumab therapy and was significantly lower on CD4(+) vs CD8(+) T cells. CONCLUSIONS: Natalizumab treatment alters the CSF CD4(+)/CD8(+) ratio. Lower expression of unbound alpha4 integrin on CD4(+) T cells is one possible mechanism. These results may have implications for the observation that some natalizumab-treated patients with MS developed progressive multifocal leukoencephalopathy.

Adolescent↗
PubMed2006

Immune surveillance in multiple sclerosis patients treated with natalizumab.

OBJECTIVE: Our objective was to test whether natalizumab, an antibody against very late activating antigen (VLA)-4, interferes with central nervous system immune surveillance as assessed by leukocyte cell numbers and cellular phenotypes in cerebrospinal fluid (CSF) and peripheral blood. METHODS: Cell numbers and cellular phenotypes in CSF and peripheral blood were analyzed in multiple sclerosis (MS) patients treated with natalizumab, untreated MS patients, and patients with other neurological disease (OND). JC virus DNA in the CSF and peripheral blood was quantified by kinetic polymerase chain reaction. RESULTS: CSF leukocyte counts, CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD138(+) plasma cells were significantly lower in natalizumab-treated MS patients compared with OND patients and untreated MS patients. JC virus DNA was not detected in CSF or peripheral blood from natalizumab-treated patients. Six months after cessation of natalizumab therapy, low lymphocyte counts in the CSF persisted. The patient with the highest total leukocyte and CD4(+) and CD8(+)T-cell counts in the CSF experienced a clinical relapse. INTERPRETATION: These data suggest that natalizumab treatment results in a prolonged decrease of lymphocytes in the CSF and are consistent with the hypothesis that natalizumab impairs immune surveillance of the central nervous system.

Adult↗
PubMed2006

Affective disorders in patients with HIV infection: impact of antiretroviral therapy.

At the beginning of the AIDS pandemic, affective disorders (such as depressed mood) were seen in a considerable number of HIV-1-infected individuals. These disorders were a result of the poor physical condition of the patients, brain involvement by the virus (e.g. encephalopathy) or a reaction to disadvantageous living conditions (losing friends, jobs, etc.). In the era of highly active antiretroviral therapy (HAART), mental illness related to physical weakness is declining, as is the incidence of HIV-1-associated encephalopathy. However, depressed mood and fatigue caused by efavirenz (a standard component of HAART) is becoming increasingly important, particularly in individuals who are infected long-term with HIV-1. Whatever the cause of affective disorders, their presence has been shown to negatively influence adherence to HAART and HIV-1 disease progression. Specialist knowledge of HIV-1 infection, and HAART and its psychiatric complications (particularly in subgroups of patients such as drug abusers and older people), is needed to care adequately for patients. Furthermore, prospective studies are needed to more fully differentiate between the various aetiologies of affective disorders seen in individuals living with HIV/AIDS and to determine their incidence and prevalence. Such information is important to ensure that affective disorders are recognised and adequately treated, which will in turn improve the efficacy of HAART.

Anti-Retroviral Agents↗
PubMed2005

Cerebrospinal fluid HIV viral load in different phases of HIV-associated brain disease.

We compared CSF HIV viral load in 33 asymptomatic HIV seropositive patients, 11 patients with incipient minor motor deficits (MMD), 11 patients with sustained MMD, and 16 patients with HIV-associated dementia. Patients with incipient MMD showed significantly higher CSF viral load than asymptomatic patients. Demented patients also had higher CSF viral loads than asymptomatic patients. This phenomenon is independent of antiretroviral therapy. Thus, correlation of viral load with time suggests a multiphasic course of HIV-associated CNS disease.

Adult↗
PubMed2005

HIV Dementia Scale and psychomotor slowing--the best methods in screening for neuro-AIDS.

The authors examined the correlation between Human Immunodeficiency Virus (HIV) Dementia Scale (HDS) and psychomotor tests, evaluating basal ganglia function in 266 HIV-seropositive, Caucasian, homosexual men. Fifty-five HIV-positive, patients with mild dementia (HDS score < or =10) showed significant slowing of most rapid alternating movements (MRAM) and significantly prolonged contraction times compared to 211 HIV-positive nondemented patients (HDS score >10). Motor performance correlated significantly with the time-dependent HDS subscores for psychomotor speed and construction and HDS sum score. In contrast to contraction times and MRAM, HDS scores also showed significant correlations to age, premorbid and actual intelligence, and duration of HIV seropositivity.

AIDS Dementia Complex↗
PubMed2004

Psychomotor slowing in hepatitis C and HIV infection.

BACKGROUND: Both HIV and hepatitis C virus (HCV) may enter the central nervous system and cause cognitive and/or motor dysfunction. There are limited data on cognition and no data on motor performance in HIV/HCV-coinfected patients. OBJECTIVE: To provide data on cognition and motor performance in HIV/HCV infected patients. METHODS: We compared 43 HIV-seropositive but HCV-seronegative patients, 43 HIV/HCV-coinfected patients, and 44 HIV-negative but HCV-positive patients, all of whom went through neuropsychologic testing and electrophysiologic assessment of basal ganglia-mediated motor function. RESULTS: No significant differences could be found among the groups with regard to premorbid verbal and actual nonverbal intelligence, attention, and memory; the HIV dementia scale; and all somatic and most psychiatric complaints. Affective disorders were less frequent in HIV-negative but HCV-positive patients. This group also scored lower for depression. For all 3 groups, significant pathologic slowing of most rapid alternating movements (right hand) compared with those of HIV/HCV-negative controls as well as significantly prolonged contraction times (both hands) could be diagnosed. Simple reaction times were significantly prolonged only in HIV/HCV-coinfected patients. CONCLUSIONS: Although clinically asymptomatic, both HIV-positive and HCV-positive patients may show affective disturbances and significant psychomotor slowing. A potential predictive value for the further course of infection, which is well established in HIV-positive patients, remains to be investigated in HCV-positive or HIV/HCV-coinfected patients.

Adult↗
PubMed2004

Serum and cerebrospinal fluid levels of interleukin-18 in human immunodeficiency virus type 1-associated central nervous system disease.

Interleukin-18 (IL-18) is a proinflammatory cytokine released by macrophages that strongly stimulates the production of interferon-gamma, thereby linking innate and acquired immunity. Its role in human immunodeficiency virus (HIV) pathogenesis is under debate and little is known about its role in neuro-AIDS (acquired immunodeficiency syndrome). Serum and cerebrospinal fluid (CSF) levels of IL-18 were determined by a commercially available enzyme-linked immunosorbent assay (ELISA) in 22 HIV-seropositive patients without neurological symptoms (HIV+), 21 patients with AIDS dementia complex (ADC), and 31 patients with AIDS-defining opportunistic infections (OIs) of the brain. Thirty-two HIV seronegative patients (HIV-) served as controls. Compared to HIV- controls, serum IL-18 levels were increased in HIV+ and ADC but not in OI patients. In contrast, CSF IL-18 levels were elevated in OI patients whereas HIV+ and ADC patients were not different from HIV- controls. We provide evidence for an significantly increased IL-18 level in the CSF of HIV+ patients with cerebral OIs, suggestive of a role for IL-18 in the intrathecal host response to OIs.

AIDS Dementia Complex↗
PubMed2004

TMC-125 Tibotec.

TMC-125, a non-nucleoside reverse transcriptase inhibitor, is being developed by Tibotec for the potential treatment of HIV infection. Phase IIa trials in treatment-naive and treatment-experienced HIV-1-infected individuals had been completed by February 2002. A long-term, phase IIb, dose-finding study in treatment-experienced patients started enroling patients in a number of European countries during 2002, and Canada during 2003.

Animals↗
PubMed2003

Human immunodeficiency virus 1-associated minor motor disorders: perfusion-weighted MR imaging and H MR spectroscopy.

PURPOSE: To investigate whether advanced magnetic resonance (MR) imaging techniques such as diffusion-weighted (DW) and perfusion-weighted (PW) MR imaging and hydrogen 1 (1H) MR spectroscopy can depict functional and pathophysiologic mechanisms in patients who have minor motor deficits (MMDs) associated with human immunodeficiency virus 1 (HIV-1). MATERIALS AND METHODS: Thirty-two patients with results seropositive for HIV-1 and different degrees of HIV-1-related MMD underwent conventional brain MR imaging, as well as DW and PW MR imaging and 1H MR spectroscopy of the basal ganglia. PW MR imaging data were computed pixel by pixel for creation of time-to-peak, relative regional cerebral blood volume, and bolus amplitude parameter maps. In addition, quantitative regional cerebral blood flow (rCBF) maps were calculated with respect to the arterial input function by using the singular value decomposition algorithm. For 1H MR spectroscopy, a stimulated echo acquisition mode 20, or STEAM 20, sequence was used. Spectra were fit for determination of the signal intensities of the different metabolites. According to psychomotor testing results, patients were divided into three groups: group 1, 10 patients with normal motor function; group 2, eight patients with psychomotor slowing for the first time; and group 3, 14 patients who had had sustained pathologic psychomotor slowing for at least 6 months before the MR imaging examination. RESULTS: No patients had an abnormality at either conventional or DW MR imaging. PW MR imaging depicted significantly elevated rCBF in group 2 patients (P =.039, analysis of variance [ANOVA]) and significantly elevated myo-inositol-to-creatine ratio levels in group 3 patients (P =.020, ANOVA). CONCLUSION: Quantitative PW MR imaging and 1H MR spectroscopy can depict pathologic changes in patients who have HIV-1-related MMD but normal clinical examination and conventional MR imaging findings.

Adult↗
PubMed2003

HIV-1-positive female migrants in Northrhine-Westphalia--relevant, but unfocussed problem?

Data of 204 HIV-1-positive female migrants from Sub-Saharan Africa, Asia and European countries other than Germany were analysed and compared to those of 282 German female virus carriers. Because not much is known about this subpopulation, the first step was to get an overview about the existing data and to describe them statistically in order to design prospective studies. A first result was that female migrants generally are tested for HIV-1 at a younger age than the control subjects. Predominant infection mode in the migrant population was heterosexual intercourse, whereas in the controls there were significantly more i.v. drug users. Distribution to the CDC-stages, CD4+-cell count and plasma viral load did not differ in both groups except for a higher percentage of AIDS-defined individuals among the controls. Surprisingly, significantly more migrants were treated with antiretroviral drugs than in the control group. However, both groups showed the same pattern of AIDS-defining diseases, only tuberculosis occurs more often in migrants. The data show that migrants are a vulnerable subpopulation which can be once being integrated in the health system of the host country effectively treated. - Results are discussed with respect to the international literature. The urgent need for adequate preventive strategies is underlined.

Adult↗
PubMed2003

Lyme borreliosis.

Lyme borreliosis is a multi-organ infection caused by spirochetes of the Borrelia burgdorferi sensu lato group with its species B burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii, which are transmitted by ticks of the species Ixodes. Laboratory testing of Lyme borreliosis includes culture, antibody detection using ELISA with whole extracts or recombinant chimeric borrelia proteins, immunoblot, and PCR with different levels of sensitivity and specificity for each test. Common skin manifestations of Lyme borreliosis include erythema migrans, lymphocytoma, and acrodermatitis chronica atrophicans. The last two conditions are usually caused by B garinii and B afzelii, respectively, which are seen more frequently in Europe than in America. Late extracutaneous manifestations of Lyme borreliosis are characterised by carditis, neuroborreliosis, and arthritis. We present evidence-based treatment recommendations for Lyme borreliosis and review the prevention of Lyme borreliosis, including the Lyme vaccines.

Adolescent↗
PubMed2003

Association of human polyomavirus JC with peripheral blood of immunoimpaired and healthy individuals.

JC virus (JCV) infection is regularly asymptomatic in healthy individuals. In contrast, in immunocompromised individuals, highly activated virus replication may lead to PML. Peripheral blood cells (PBCs) are found to harbor JCV DNA in healthy and diseased individuals and it is discussed that they might be responsible for dissemination of the virus to the central nervous system (CNS) during persistence. To better understand the role of JCV DNA in PBCs for persistent infection and pathogenesis, the authors characterized the extent of JCV infection in Ficoll-gradient purified blood cells (peripheral blood mononuclear cells [PBMCs]) of healthy and human immunodeficiency virus type 1 (HIV-1)-infected individuals. Virus activation in PBMCs from healthy JCV-infected individuals was found at a rate of 0% to 38% at low polymerase chain reaction (PCR) sensitivity. In progressive multifocal leukoencephalopathy (PML) patients, a stronger signal was found, indicating increased virus activation. JCV DNA was regularly detected in T and B lymphocytes and in monocytes at low levels. However, granulocytes were shown to be the predominant reservoir of JCV DNA harboring high copy numbers. Although the overall distribution of viral genomes holds true for the population studied, in the individual, a markedly changed pattern of distribution can be found.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Increased intrathecal release of soluble fractalkine in HIV-infected patients.

The CX(3)C chemokine fractalkine is suggested to play an important role in inflammatory brain diseases, for example, because of its chemotactic properties. To investigate the release of soluble fractalkine in HIV-induced brain diseases fractalkine levels were determined in cerebrospinal fluid (CSF) and serum samples of HIV-infected patients with (n = 10) and without (n = 23) HIV-induced CNS complications, using semiquantitative Western blot analysis. Fractalkine CSF levels were significantly elevated (p < 0.05) in HIV-infected patients with CNS diseases compared with those without, and compared with HIV-negative controls (n = 23). Fractalkine serum concentrations did not differ between the two groups of HIV-infected patients, but were significantly elevated (p < 0.05) in HIV-infected patients with CNS complications compared with HIV-negative controls. Levels of fractalkine did not correlate with the CSF and serum HIV load and other CSF parameters. In one patient with HIV-associated dementia and myelopathy CSF fractalkine levels decreased on initiation of antiretroviral therapy and subsequent clinical improvement. In conclusion, intrathecal fractalkine release was observed in the majority of patients with HIV infection. The highest levels of soluble fractalkine were detected in CSF (and serum) samples of patients with HIV-induced CNS disorders. These results suggest a dysregulation of brain soluble fractalkine release during HIV infection.

AIDS Dementia Complex↗
PubMed2002

Therapeutic effects of nonnucleoside reverse transcriptase inhibitors on the central nervous system in HIV-1-infected patients.

Psychomotor slowing predicts the development of HIV-1-associated dementia, AIDS, and death independent of immune status. We retrospectively selected all patients who showed pathologic psychomotor slowing as a sign of central nervous system (CNS) dysfunction before the onset of therapy and who were then treated with nonnucleoside reverse-transcriptase inhibitors-either efavirenz (EFV) (n = 65 patients) or nevirapine (NVP) (n = 39 patients), each given in combination with two nucleoside analogues (NAs). Patients who were treated only with two NAs (n = 66) served as controls. Patients were observed for 6 months. Both EFV and NVP combinations improved CNS function as determined by electrophysiologic motor tests. The therapeutic effects of EFV and NVP did not depend on the type of NA added. Although results did not reach significance, NVP combinations were more effective than EFV combinations or therapy regimens with NAs alone in patients who were naïve to all antiretroviral therapy. EFV and NVP combinations were equally effective in patients pretreated with highly active antiretroviral therapy, including protease inhibitors.

Adult↗
PubMed2002

Central and peripheral nervous system functions are independently disturbed in HIV-1 infected patients.

We examined the peripheral nervous system (PNS) (nerve conduction velocity (NCV)) and the central nervous system (CNS) (basal ganglia-mediated psychomotor speed) in 93 males seropositive for human immunodeficiency virus type 1 (HIV-1) with no prior history of opportunistic brain disease, antiretroviral treatment or intravenous drug use. Patients with different degrees of slowing of peroneal and sural NCV showed no significant differences in psychomotor speed as assessed by tremor peak frequency, most rapid alternating movements, reaction times and contraction times. There was no significant correlation between psychomotor measures and NCV. Psychomotor slowing test findings were independent from peripheral nervous system damage indicating uncorrelated disturbances of CNS and PNS function in HIV-1 infection. Differences in HIV-1 viral quasispecies or host responses may determine the predominance of CNS or PNS injury.

AIDS Dementia Complex↗
PubMed2002

Functional CXCR4 receptor development parallels sensitivity to HIV-1 gp120 in cultured rat astroglial cells but not in cultured rat cortical neurons.

The alpha chemokine receptor CXCR4 is used as the major coreceptor for the cell entry of T-cell-tropic human immunodeficiency virus-1 (HIV-1) isolates. Activation of this coreceptor by its natural ligand SDF1alpha is associated with an intracellular Ca(2+) increase. Because the HIV-1 glycoprotein 120 (gp120) is shedded from the surface of HIV-1-infected cells and is regarded as an injurious molecule in the pathogenesis of HIV-1-associated encephalopathy (HIVE), we investigated the effects of gp120 on the intracellular Ca(2+) regulation of astrocytes and neurons. After 5 days in vitro (DIV), SDF1alpha (50 nM) elicited a pertussis toxin-sensitive intracellular Ca(2+) increase due to Ca(2+) release from internal stores that was reduced by a blocking monoclonal antibody against the CXCR4 receptor in astrocytes and neurons. Parallel with the development of the SDF1alpha response, cells became sensitive to direct application of gp120 (1.25 microg/ml), which, similarly to SDF1alpha, elicited a transient intracellular Ca(2+) increase. However, short-term incubation with gp120 for 60 to 120 min induced a reduction of glutamate- or ATP-evoked intracellular Ca(2+) responses only in astrocytes and not in neurons, although functional CXCR4 receptors were expressed in both cell types. Therefore, our data strongly suggest that the CXCR4 receptor-mediated intracellular signaling pathway of gp120 differs in astrocytes and neurons.

AIDS Dementia Complex↗