Human cytomegalovirus (HCMV) long-term shedding and HCMV-specific immune response in pregnant women with primary HCMV infection.

Human cytomegalovirus (HCMV) shedding has been extensively investigated in newborns and in young children, however, much less is known about it in immunocompetent adults. Shedding of HCMV was investigated in saliva, vaginal secretions and urine of pregnant women experiencing primary infection along with the development of the HCMV-specific immune response. Thirty-three pregnant women shed HCMV DNA in peripheral biological fluids at least until one year after onset of infection, while in blood HCMV DNA was cleared earlier. Significantly higher levels of viral load were found in vaginal secretions compared to saliva and urine. All subjects examined two years after the onset of infection showed a high avidity index, with IgM persisting in 36% of women. Viral load in blood was directly correlated with levels of HCMV-specific IgM and inversely correlated with levels of IgG specific for the pentameric complex gH/gL/pUL128L; in addition, viral load in blood was inversely correlated with percentage of HCMV-specific CD4+ and CD8+ expressing IL-7R (long-term memory, LTM) while viral load in biological fluids was inversely correlated with percentage of HCMV-specific CD4+ and CD8+ effector memory RA+(TEMRA). In conclusion, viral shedding during primary infection in pregnancy persists in peripheral biological fluids for at least one year and the development of both antibodies (including those directed toward the pentameric complex) and memory T cells are associated with viral clearance.

Inconsistent responses of cytomegalovirus-specific T cells to pp65 and IE-1 versus infected dendritic cells in organ transplant recipients.

CD4(+) and CD8(+) T cells specific for human cytomegalovirus (HCMV) and two immunodominant HCMV antigens (pp65 and IE-1) were monitored in 20 solid organ transplant recipients undergoing primary (n = 4) or reactivated (n = 16) HCMV infection during the first year after transplantation by using as a stimulator either HCMV-infected autologous dendritic cells (DCs) or pp65- or IE-1 peptide mixtures. Turnaround times for test performance were 7 days for infected DCs and 24 h for peptides. Using infected DCs, HCMV-specific T-cell restoration occurred in all patients for CD8(+) and in 18/20 (90%) for CD4(+) T-cell subpopulations, resulting in virus clearance from blood. Using peptide mixtures, T-cell responses were less frequently detected. In detail, 14 (70%) patients showed pp65-specific CD8(+) T cells and 10 (50%) patients IE-1-specific CD8(+) T cells, whereas pp65-specific CD4(+) T cells were detected in 14 (70%) patients, and IE-1-specific CD4(+) T cells in three (15%) patients only. Protection from HCMV infection was associated with the presence of a HCMV-specific T-cell response directed against multiple viral proteins, but not against pp65 or IE-1 only. In conclusion, the use of pp65 and IE-1 peptide mixtures for rapid monitoring of HCMV-specific T-cell responses in solid organ transplant recipients underestimates the actual T-cell immune response against HCMV.

Control of human cytomegalovirus infection in patients infected with human immunodeficiency virus by high levels of specific CD8+ T-cells.

A new technique was used to simultaneously determine human cytomegalovirus (HCMV)-specific CD4(+) and CD8(+) T-cells in highly active anti-retroviral therapy (HAART)-naive and HAART-treated patients infected with human immunodeficiency virus (HIV). HIV-infected patients with HCMV infection, but without HCMV disease, showed low numbers of HCMV-specific CD4(+) cells and high numbers of CD8(+) T-cells, both before and during HAART. HIV-infected patients with HCMV disease had no HCMV-specific CD4(+) T-cells and extremely low levels of CD8(+) T-cells. Resolution of disease during HAART was associated with rescue of specific CD4(+) T-cells and a large increase in the specific CD8(+) T-cell count. Thus, HAART does not completely restore the normal immune function. In HIV-infected patients, sustained control of HCMV infection requires high frequencies of specific CD8(+) T-cells.

Monitoring of human cytomegalovirus-specific CD4 and CD8 T-cell immunity in patients receiving solid organ transplantation.

Absolute and human cytomegalovirus (HCMV)-specific CD4+ and CD8+ T-cell counts were monitored in 38 solid organ (20 heart, 9 lung and 9 kidney) transplant recipients during the first year after transplantation by a novel assay based on T-cell stimulation with HCMV-infected autologous dendritic cells. According to the pattern of T-cell restoration occurring either within the first month after transplantation or later, patients were classified as either early (n = 21) or late responders (n = 17). HCMV-specific CD4+ and CD8+ T-cell counts were consistently lower in late compared to early responders from baseline through 6 months after transplantation. In addition, in late responders, while HCMV infection preceded immune restoration, HCMV-specific CD4+ restoration was significantly delayed with respect to CD8+ T-cell restoration. The number of HCMV-specific CD4+ and CD8+ T-cells detected prior to transplantation significantly correlated with time to T-cell immunity restoration, in that higher HCMV-specific T-cell counts predicted earlier immune restoration. Clinically, the great majority of early responders (18/21, 85.7%) underwent self-resolving HCMV infections (p = 0.004), whereas the great majority of late responders (13/17, 76.5%) were affected by HCMV infections requiring antiviral treatment (p = <0.0001). Simultaneous monitoring of HCMV infection and HCMV-specific T-cell immunity predicts T-cell-mediated control of HCMV infection.

Abnormal pattern of cortical activation associated with voluntary movement in obsessive-compulsive disorder: an EEG study.

OBJECTIVE: Converging evidence in patients with obsessive-compulsive disorder (OCD) shows abnormalities of prefrontal areas and basal ganglia, which are also involved in motor control. Event-related desynchronization of mu and beta EEG rhythms is considered a correlate of motor activation during motor preparation and execution, followed by cortical idling or inhibition indicated by event-related synchronization. The authors investigated the circuits involved in motor behavior in OCD by using event-related desynchronization/synchronization. METHOD: Data on alpha and beta event-related desynchronization/synchronization with self-paced movement of the right thumb were obtained by using 29-channel EEG in 10 untreated OCD patients and 10 normal subjects. RESULTS: OCD patients showed delayed onset of mu event-related desynchronization with movement preparation and less postmovement beta synchronization, compared to normal subjects. CONCLUSIONS: Delayed event-related desynchronization in OCD is consistent with involvement of structures related to motor programming, such as basal ganglia. Lower levels of postmovement beta synchronization suggest impairment of the inhibitory system in OCD.

Computer-assisted EEG monitoring during carotid endarterectomy.

The purpose of this study was to develop a reliable method of EEG analysis during carotid endarterectomy. EEGs of 104 patients under general anesthesia were processed by three different methods: a) "on-line" visual analysis during surgery, b) "off-line" visual analysis in laboratory, and c) computer analysis. To identify pathological EEGs, variability and asymmetry indexes of the 0.5-3.5 Hz and 8-15 Hz bands, absolute power and variability indexes of spectral edge frequency (SEF), and main dominant frequency were evaluated. On-line visual analysis showed clamp-related modifications in 29 EEGs (27.9%). Off-line visual analysis detected 24 pathological EEGs (23.1%): 18 with major changes and 6 with moderate changes. Computer analysis showed 21 EEGs (20.19%) with at least one altered index and 7 (6.7%) with altered variability for both SEF and 8-15 Hz power. The statistical analysis was significant for SEF variability and for 8-15 Hz power variability and asymmetry (P < 0.0001, analysis of variance test). While SEF and 8-15 Hz power variability did not appear influenced by anesthesia and single electrode artifacts, 8-15 Hz power asymmetry index was confounded by the presence of contralateral internal carotid occlusion. The data show that the use of these spectral indexes adds objective information to visual analysis, supporting and making easier intraoperative strategies. Their routine clinical use does not involve additional costs remaining technical requirements unchanged compared to traditional recording.

Cognitive function and neurophysiological evaluation in early-treated hypothyroid children.

In this study, we assessed cognitive function and neurophysiological development in congenitally hypothyroid (CH) children. We performed a cross-sectional study at the outpatient Pediatric Clinic and Department of Neurophysiology at San Raffaele Hospital, Milan. The study enrolled 25 CH patients (6.00-10.83 years of age) detected by neonatal screening, and 34 healthy control children (4-11 years of age). Patients and controls had comparable scores at neuropsychological tests (WISC-R), and at auditory P300 tests. In contrast, we found significantly longer LLSEP latencies in CH patients (p < 0.03). CH patients treated 30 days after birth showed lower scores at neuropsychological tests, but not at neurophysiological tests, compared to patients who started the replacement therapy earlier. Patients with more severe fetal hypothyroidism (T4 levels at diagnosis < or = 2 micrograms/dl) had lower neuropsychological scores, and similar neurophysiological results, compared with patients with moderate fetal hypothyroidism. The severity of fetal hypothyroidism and early treatment influence the mental outcome of CH patients. Neurophysiological results show that central nervous system damage occurs in some patients despite early treatment.

FFT approximation in Alzheimer's disease.

The electroencephalographic modifications that occur during the course of Alzheimer's disease are characterised by an increase in the potential of low frequency bands, a diminution in the potential of alpha activity, and a change in the topographical distribution of the potential of all band frequencies. In this study, the fast Fourier transform (FFT) approximation was used to characterise modifications in the electroencephalogram location or orientation of the source of the dipole equivalent of the delta, theta, alpha1, alpha2, beta1 and beta2 frequencies in 20 with patients with Alzheimer's disease and in a control group of 20 age-matched subjects. A statistical (t-test) comparison of the two groups revealed a significant change in the location of the dipolar source along the vertical axis in 18 (90%) of the patients; this change involved all the frequency bands. There was also a significant movement of the dipolar source of the alpha1 band towards the anterior regions. In addition, the control group showed that there was a significant correlation between age and a more surface expression of the source of the delta, theta, alpha1 and beta1 bands.

Varicella-zoster virus (VZV) DNA in cerebrospinal fluid of patients infected with human immunodeficiency virus: VZV disease of the central nervous system or subclinical reactivation of VZV infection?

To identify varicella-zoster virus (VZV) infections of the nervous system in patients infected with human immunodeficiency virus (HIV), polymerase chain reaction (PCR) analysis of cerebrospinal fluid (CSF) samples from 514 consecutive HIV-infected patients with neurological disease was performed to detect VZV DNA. VZV DNA was detected in CSF of 13 (2.5%) of 514 patients. Four of 13 patients had VZV encephalitis or meningoencephalomyelitis. These four patients received intravenous acyclovir therapy; CSF became negative for VZV DNA and clinical conditions improved for two, whereas CSF remained positive for VZV DNA and clinical conditions worsened until death for two. In nine of 13 patients, the neurological symptoms were likely caused by other simultaneous HIV-related complications in the central nervous system. After intravenous therapy with high doses of acyclovir or foscarnet, VZV was cleared from CSF in eight of nine patients. VZV DNA can be detected in CSF of HIV-infected patients in association with either manifestations of neurological VZV disease or subclinical reactivation of VZV infection. Antiviral treatment may be effective in suppressing VZV replication in the nervous system.

Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients.

OBJECTIVE: To assess the diagnostic reliability of polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) for virus-associated opportunistic diseases of the central nervous system (CNS) in HIV-infected patients. DESIGN: CSF samples from 500 patients with HIV infection and CNS symptoms were examined by PCR. In 219 patients the PCR results were compared with CNS histological findings. METHODS: Nested PCR for detection of herpes simplex virus (HSV) type 1 or 2, varicella zoster virus (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and JC virus (JCV) DNA. Histopathological examination of CNS tissue obtained at autopsy or on brain biopsy. RESULTS: DNA of one or more viruses was found in CSF in 181 out of 500 patients (36%; HSV-1 2%, HSV-2 1%, VZV 3%, CMV 16%, EBV 12%, HHV-6 2%, and JCV 9%). Among the 219 patients with histological CNS examination, HSV-1 or 2 was detected in CSF in all six patients (100%) with HSV infection of the CNS, CMV in 37 out of 45 (82%) with CMV infection of the CNS, EBV in 35 out of 36 (97%) with primary CNS lymphoma, JCV in 28 out of 39 (72%) with progressive multifocal leukoencephalopathy. Furthermore, HSV-1 was found in one, VZV in four, CMV in three, EBV in three, HHV-6 in seven, and JCV in one patient without histological evidence of the corresponding CNS disease. CONCLUSIONS: CSF PCR has great relevance for diagnosis of virus-related opportunistic CNS diseases in HIV-infected patients as demonstrated by its high sensitivity, specificity, and the frequency of positive findings.

Tratamento prolongado da vaginite atrófica pelo promestriene: resultados e tolerância / Prolonged treatment of athrophic vaginitis with promestriene: results and tolerance

Vinte pacientes menopausadas portadoras de vaginite atrófica com ausência de células superficiais ao esfregaço cito-hormonal foram tratadas durante quatro a seis meses, através de terapias mensais de 20 dias, com cápsulas vaginais de promestriene. O tratamento proporcionou modificaçäo significativa da citologia vaginal, que consistiu principalmente no desenvolvimento das células intermediárias às custas das células basais. Näo houve elevaçäo da taxa plasmática do estradiol e näo foi observada qualquer modificaçäo nos parâmetros clínicos e biológicos examinados. Tais conclusöes foram estatisticamente significativas. O estudo confirmou também a boa tolerância do promestriene administrado em tratamentos prolongados e/ou repetidos, freqüentemente necessários nas pacientes menopausadas.