Changes in brain activity with tominersen in early-manifest Huntington's disease.

It is unknown whether alterations in EEG brain activity caused by Huntington's disease may be responsive to huntingtin-lowering treatment. We analysed EEG recordings of 46 patients (mean age = 47.02 years; standard deviation = 10.19 years; 18 female) with early-manifest Stage 1 Huntington's disease receiving the huntingtin-lowering antisense oligonucleotide tominersen for 4 months or receiving placebo as well as 39 healthy volunteers (mean age = 44.48 years; standard deviation = 12.94; 22 female) not receiving treatment. Patients on tominersen showed increased resting-state activity within a 4-8 Hz frequency range compared with patients receiving placebo (cluster-based permutation test, P < 0.05). The responsive frequency range overlapped with EEG activity that was strongly reduced in Huntington's disease compared with healthy controls (cluster-based permutation test, P < 0.05). The underlying mechanisms of the observed treatment-related increase are unknown and may reflect neural plasticity as a consequence of the molecular pathways impacted by tominersen treatment. Hawellek et al. report that patients with Huntington's disease treated with the huntingtin-lowering antisense oligonucleotide tominersen exhibited increased EEG power in the theta/alpha frequency range. The underlying mechanisms of the observed changes are unknown and may reflect neural plasticity as a consequence of the molecular pathways impacted by tominersen treatment.

Spatiotemporal Oscillatory Patterns During Working Memory Maintenance in Mild Cognitive Impairment and Subjective Cognitive Decline.

Working memory (WM) is a crucial cognitive process and its disruption is among the earliest symptoms of Alzheimer's disease. While alterations of the neuronal processes underlying WM have been evidenced in mild cognitive impairment (MCI), scarce literature is available in subjective cognitive decline (SCD). We used magnetoencephalography during a WM task performed by MCI (n = 45), SCD (n = 49) and healthy elders (n = 49) to examine group differences during the maintenance period (0-4000ms). Data were analyzed using time-frequency analysis and significant oscillatory differences were localized at the source level. Our results indicated significant differences between groups, mainly during the early maintenance (250-1250ms) in the theta, alpha and beta bands and in the late maintenance (2750-3750ms) in the theta band. MCI showed lower local synchronization in fronto-temporal cortical regions in the early theta-alpha window relative to controls (p = 2 × 10-03) and SCD (p = 4 × 10-03), and in the late theta window relative to controls (p = 1 × 1003) and SCD (p = 0.01). Early theta-alpha power was significantly correlated with memory scores (rho = 0.24,p = 0.02) and late theta power was correlated with task performance (rho = 0.24,p = 0.03) and functional activity scores (rho = -0.23,p = 0.02). In the early beta window, MCI showed reduced power in temporo-posterior regions relative to controls (p = 3 × 10-03) and SCD (p = 0.02). Our results may suggest that these alterations would reflect that memory-related networks are damaged.

The Effect of Different Oxygen Surface Functionalization of Carbon Nanotubes on the Electrical Resistivity and Strain Sensing Function of Cement Pastes.

Different studies in the literature indicate the effectiveness of CNTs as reinforcing materials in cement-matrix composites due to their high mechanical strength. Nevertheless, their incorporation into cement presents some difficulties due to their tendency to agglomerate, yielding a non-homogeneous dispersion in the paste mix that results in a poor cement-CNTs interaction. This makes the surface modification of the CNTs by introducing functional groups on the surface necessary. In this study, three different treatments for incorporating polar oxygen functional groups onto the surface of carbon nanotubes have been carried out, with the objective of evaluating the influence of the type and oxidation degree on the mechanical and electrical properties and in strain-sensing function of cement pastes containing CNTs. One treatment is in liquid phase (surface oxidation with HNO3/H2SO4), the second is in gas phase (O3 treatment at 25 and 160 °C), and a third is a combination of gas-phase O3 treatment plus NaOH liquid phase. The electrical conductivity of cement pastes increased with O3- and O3-NaOH-treated CNTs with respect to non-treated ones. Furthermore, the oxygen functionalization treatments clearly improve the strain sensing performance of the CNT-cement pastes, particularly in terms of the accuracy of the linear correlation between the resistance and the stress, as well as the increase in the gage factor from 28 to 65. Additionally, the incorporation of either non-functionalized or functionalized CNTs did not produce any significant modification of the mechanical properties of CNTs. Therefore, the functionalization of CNTs favours the de-agglomeration of CNTs in the cement matrix and consequently, the electrical conductivity, without affecting the mechanical behaviour.

Autologous attenuated T-cell vaccine (Tovaxin) dose escalation in multiple sclerosis relapsing-remitting and secondary progressive patients nonresponsive to approved immunomodulatory therapies.

An open-label dose escalation study of T-cell vaccination in multiple sclerosis patients was conducted using attenuated myelin reactive T-cells (MRTC) selected with six myelin peptides, two each from MBP, PLP and MOG. The dose range of subcutaneous injections given at weeks 0, 4, 12 and 20 was 6-9E6, 30-45E6 and 60-90E6 irradiated MRTC. Assessments were over 52 weeks for MRTC levels, EDSS, MSIS-29, brain MRI and relapses. The 30-45E6 dose was the most effective with reductions in MRTC ranging from 92.4% at week 5 to 64.8% at week 52. The reduction in relapses compared to baseline for the M-ITT and evaluable per-protocol analyses were 63.5%, and 85.0% at week 52. The MRI lesions were stable while there was an improvement trend in the EDSS and MSIS-29 physical subscore following the second injection. Adverse events were mild to moderate in intensity with mild injection site reactions occurring with increasing dosage. The mid-dose was selected for further clinical development studies because of the rapid depletion of peripheral blood MRTC and a trend for improvements in clinical outcomes following immunization.

Electrophysiological assessment methodology of sensory processing dysfunction in schizophrenia and dementia of the Alzheimer type.

Schizophrenia and Alzheimer's disease impacts on various sensory processings are extensively reviewed in the present publication. This article describes aspects of a research project whose aim is to delineate the neurobiology that may underlie Social Withdrawal in Alzheimer's disease, Schizophrenia and Major Depression. This is a European-funded IMI 2 project, identified as PRISM (Psychiatric Ratings using Intermediate Stratified Markers). This paper focuses specifically on the selected electrophysiological paradigms chosen based on a comprehensive review of all relevant literature and practical constraints. The choice of the electrophysiological biomarkers were fundamentality based their metrics and capacity to discriminate between populations. The selected electrophysiological paradigms are resting state EEG, auditory mismatch negativity, auditory and visual based oddball paradigms, facial emotion processing ERP's and auditory steady-state response. The primary objective is to study the effect of social withdrawal on various biomarkers and endophenotypes found altered in the target populations. This has never been studied in relationship to social withdrawal, an important component of CNS diseases.

Mechanical and physical properties of cement blended with sewage sludge ash.

The aim of this paper is to evaluate the compatibility of sewage sludge ash (SSA) with various types of commercially available cements (CEM I and CEM II types, cements with several proportions of clinker). The behaviour of mortars fabricated with various percentages (10-30% by weight) of the cement replaced by SSA has been analyzed in terms of workability, mechanical strength, porosity and shrinkage/expansion. SSA exhibits moderate pozzolanic activity; the highest compressive strengths were obtained with 10% of the cement replaced by SSA. The CEM II/B-M (V-LL) 42.5R cement is considered ideal for preparing mortars containing SSA. Shrinkage data demonstrate that sulphates present in SSA are not reactive towards cement.

[Lowering plasma homocysteine with vitamins B6, B12, and folic acid. Effect on lipids concentration in patients with secondary hyperlipoproteinemia type IV, with and without Lovastatina treatment]. / Disminución de homocisteina plasmática con vitaminas B6, B12 y ácido fólico. Su efecto en la concentración de los lípidos en pacientes con hiperlipoproteinemia secundaria tipo IV, con y sin tratamiento con lovastatina.

The concentration of plasma homocysteine was diminished by the oral use of vitamins B6 (300 mg/day), B12 (250 microg/day) and folic acid (10 mg/day), and the effect was studied in the lipids of patient with hiperlipoproteinemia secondary type IV, during 120 days, in 30 patients, 45 to 70 years old, with myocardial heart attack. They were divided in group A (n=15) without treatment with Lovastatin and group B (n=15) with Lovastatin. Basal homocysteine concentration was 17.4 +/- 1.0 micromol/L and 16.7 +/- 1.0 micromol/L for the groups A and B respectively, diminishing 24% at the end of the experimental time, in both groups. Total cholesterol decreased below 220 mg/dl, while the triglycerides diminished 25.4 mg/dl and 27.0 mg/dl in groups A and B respectively, by each micromol/L of homocysteine catabolissed. Low density lipoproteins (LDL) and very low density (VLDL) diminished significantly (p < 0.005), while the high-density (HDL) increased 1.0 mg/dl in group A and 1.15 mg/dl in group B, for each micromol/L of homocysteine metabolized, lowering the coronary risk factor in 28.5% group A and 35.9% group B. We concluded that these vitamins decreased plasma homocysteine concentration, promoting the lowering of lipids and lipoprotein concentratation in this type of patients; while Lovastatin doesn't reduce homocysteine, but it had a synergic effect with the vitamins, dicreasing the lipid concentration, in group B.

Alpha band disruption in the AD-continuum starts in the Subjective Cognitive Decline stage: a MEG study.

The consideration of Subjective Cognitive Decline (SCD) as a preclinical stage of AD remains still a matter of debate. Alpha band alterations represent one of the most significant changes in the electrophysiological profile of AD. In particular, AD patients exhibit reduced alpha relative power and frequency. We used alpha band activity measured with MEG to study whether SCD and MCI elders present these electrophysiological changes characteristic of AD, and to determine the evolution of the observed alterations across AD spectrum. The total sample consisted of 131 participants: 39 elders without SCD, 41 elders with SCD and 51 MCI patients. All of them underwent MEG and MRI scans and neuropsychological assessment. SCD and MCI patients exhibited a similar reduction in alpha band activity compared with the no SCD group. However, only MCI patients showed a slowing in their alpha peak frequency compared with both SCD and no SCD. These changes in alpha band were related to worse cognition. Our results suggest that AD-related alterations may start in the SCD stage, with a reduction in alpha relative power. It is later, in the MCI stage, where the slowing of the spectral profile takes place, giving rise to objective deficits in cognitive functioning.

[Infantile bilateral striate necrosis]. / Necrosis estriatal bilateral infantil.

INTRODUCTION: Necrosis of the basal ganglia (NBG) is an uncommon condition in childhood. Cases of NBG have been reported in connection with metabolic disorders, infections, degenerative conditions, intoxications, head injuries and hypoxic-ischemic encephalopathies. The commonest clinical features include alteration of consciousness, chorea-athetoic or dystonic movements, spasticity, contractures of the limbs and convulsions. CLINICAL CASE: We describe the case of an eight year old girl, who after having clinical gastroenteritis, developed acute neurological dysfunction, associated with images on cranial computerized axial tomography (CAT) showing a possible intracranial tumour and magnetic resonance (MR) studies showing bilateral hypodensity of the basal ganglia. Three months later magnetic resonance showed that these lesions had almost completely disappeared. This supports the diagnosis of post-infectious lesions. CONCLUSIONS: The clinical course is very variable. Cases with a previous history of infection have a better prognosis. In our patient treatment was started with corticosteroids. She made a good recovery and was sent home with no sequelae five days later. The new imaging techniques (CAT and MR) have led to more cases of selective involvement of the basal ganglia being diagnosed. MR is the most specific technique for diagnosis in these patients. Although there is no effective specific treatment, treatment with biperidine, thyrotropic hormone and corticosteroids have been used with no apparent effect on the course of the disorder.

[Clinical course of cytomegalovirus retinitis with the different antiretroviral therapies in our hospital]. / Evolución de la retinitis por citomegalovirus con las diferentes terapias antirretrovirales en nuestro hospital.

PURPOSE: A study of protease inhibitors on CMV retinitis in HIV infected hospital patients. METHOD: A retrospective study was performed in 485 diagnosed of AIDS, between January, 1990 and December 1998. Among those, 81 patients who were diagnosed of CMV retinitis, the following was studied: anti-retroviral treatment, anti CMV treatment, survival time and CD4 lymphocyte count. RESULTS: Treatment with protease inhibitors in HIV patients showed an increase in life expectancy, reduced the incidence of CMV retinitis and a reduction in CMV retinitis prevention treatment was observed. CONCLUSIONS: Treatment with protease inhibitors has reduced the rate of CMV retinitis in HIV patients.

[The study of contacts of tuberculosis patients]. / Estudio de contactos con enfermos tuberculosos.

The study and follow-up of contacts is one of the main goals of the battle against tuberculosis. We studied 640 contacts of 141 patients diagnosed of active pulmonary tuberculosis (PT) in our center between 1985 and June 1990. The average per index case (IC) was 4.5. Contacts were classified according to the IC bacteriology (positive bacilloscopy and culture: 448 cases; negative bacilloscopy and positive culture: 126 cases; and both tests negative: 66 cases). PPD was positive in 342 cases (53.4%) and the number of infected contacts was significant when IC showed positive bacilloscopy and culture (251 cases), cough (328 cases). Twelve new cases of tuberculosis (1.9%) were detected, with an average age of 29.6 years. Chemoprophylaxis was completed during one-year period by 121 contacts (43.5%). The systematic study of contacts allow us to detect new patients and infected cases, helping to break the epidemiological chain of transmission of the disease.

[Characteristics of the carriers of antibodies to hepatitis C virus with normal transaminases levels in HIV infected patients]. / Características de los portadores de anticuerpos frente al virus de la hepatitis C con transaminasas normales en infectados por el VIH.

BACKGROUND: To know the characteristics of the carriers of antibodies to hepatitis C virus (HCV) with persistently normal transaminases levels ("carriers") in coinfected with HIV, the incidence of the real viral activity and the factors that could determine it. PATIENTS AND METHODS: We analyzed 114 patients with criteria for chronic hepatitis C, 41 with detectable antibodies (anti-HCV), but without chemical evidence of a deteriorations of the liver function, all of them infected with HIV. In 6 patients was possible to determine the genotype of the HCV (INNO-LiPA HCV Innogenetics. Belgica) and in 32 the HCV-RNA (Amplicor HCV Roche Diagnostics). We compared the characteristics that could be differential between both groups, investigating the possible factors that could define the group of "carriers" with detectable viral activity. RESULTS: From the 32 "carriers" in which we could determine the HCV-RNA, 15 (46.8%) had a positive result. The incidence of women in the "carriers" group was higher (41.4% vs 22.8%) (p < 0.05). The serum levels of gammaglobulin (gr/dl) was higher in the chronic hepatitis group (2.23 +/- 0.6 vs 1.9 +/- 0.5) (p < 0.01); however, these levels were higher for the 15 patients RNA (-) patients (2.19 +/- 0.7 vs 1.66 +/- 0.41) (p < 0.01). The genotype distribution of HCV found in the "carriers" group with detectable viremia was: genotype 1(5 patients), subtype la (3 patients), subtype lb (2 patients) an genotype 3 (3 patients). There was no significant difference with respect to age, sex, degree of immunosuppression or the length of the infection with HCV. CONCLUSIONS: Approximately half of our "carriers" of anti-HCV without evidence of changes in the liver function, infected with HIV, show detectable viremia and so probably liver biopsy would be indicated. Women are more often "carriers" and the high levels of gammaglobulin could define the existence of a real viral activity.

[Viremia levels of the chronic hepatitis c virus in HIV infected patients, clinical implications]. / Niveles de viremia del virus de la hepatitis crónica C en infectados por el virus de inmunodeficiencia humana. Implicaciones clínicas.

BACKGROUND: To know the clinical implications of the viremia level and its evolution in time of the hepatitis C virus (HCV) in patients with chronic hepatitis and infected with the Human Immunodeficiency Virus (HIV). PATIENTS AND METHODS: We have studied the viremia level of the HCV in a a 38 patients group with active chronic hepatitis and infected with the HIV, using a quantitative PCR technic (Amplicor HCV, Roche Diagnostics); we had histological data in 33 of these patients. In 20 patients was analyzed the evolution in time of the viremia level with two or three serialized measurements (20 and 10 patients respectively), throughout 7.5 and 14.8 months on the average. We have analyzed some aspects like the risky behaviors associated with transmission, the estimated time from the contagious, the degree of histological damage and the immunitary impairment. RESULTS: We have observed a tendency to present a higher viremia level (logarithmic expression) with longer evolution time from the infection (p = 0.08). The viral load had an inverse relation with the degree of histological fibrosis (Light fibrosis: 4.5 +/- 0.8 log vs Severe fibrosis: 3.7 +/- 0.8 log) (p < 0.01) and a direct relation with the Knodell histological activity index (HAI), only with those patients with a lower fibrosis degree (p < 0.01). There was no relation between the viremia level of the HCV and the degree of immunosuppression measured by the CD4 lymphocyte count, at least in those patients in which it was higher than 200/mm3. We have not observed relations between the viral load and the age or the transaminases level. The evolution in time of the viremia tended to rise from 3.7 +/- 1.3 to 4.5 +/- 0.9 log in 14.8 months on the average, although there were some cases with tendency to decrease. We have not observed relation between its increase/month and the degree of histological damage or the CD4 lymphocyte count. CONCLUSIONS: The viral load of the HCV in HIV-infected patients seems to have an inverse relation with the degree of liver fibrosis and direct relation with the histological activity when the fibrosis light and so it could indirectly inform us about the liver aggression. The degree of immunosuppression measured by the CD4 lymphocyte count, when these are > 200/mm3, doesn't seem to influence the viremia level of the HCV. The evolution of the viral load in time tend to rise although there could be some cases with intermittent or descending evolution, without these tendencies have any clinical implications.

[Pulmonary tuberculosis: differences between patients seropositive and seronegative for the acquired immunodeficiency virus]. / Tuberculosis pulmonar: diferencias entre pacientes seropositivos y seronegativos para el virus de la inmunodeficiencia adquirida.

423 cases of pulmonary tuberculosis (PT) are described, dividing them into two major groups depending on the presence (Group 1:54 cases) or the absence (Group 2:369 cases) of infection by the Acquired Immunodeficiency Virus, in order to compare their clinical-epidemiological characteristics. 70.37% patients of Group 1 had an age between 15 and 30 years and 72.2% (39 cases) were parenterally drug addicts. In the Group 1, fever, general and digestive symptoms were predominant (p < 0.004, p < 0.01 and p, 0.00001); a miliar profile was observed in 8 cases (14.8%) and the radiology was normal in 7 cases (12.9%), with predominance of condensation semiology and cavitation in Group II (p < 0.003 and p < 0.00001). In addition, we observed extrapulmonary affection in 42.6% cases (23 patients) of Group I (p < 0.0004) and the diagnosis of tuberculosis determined the presence of AIDS in 26 cases (48.1%).

[Tuberculosis caused by Mycobacterium bovis: apropos of 2 cases]. / Tuberculosis causada por Mycobacterium bovis: a propósito de dos casos.

Infection by Mycobacterium bovis is currently a rare form of tuberculosis in developed countries, being its incidence lower than 1%. Its main mechanism of transmission is through the ingestion of contaminated milk. In this paper, two cases of tuberculosis by Mycobacterium bovis are described, one of lymphatic location by endogenous reactivation and another of pulmonary location, probably by a primary infection acquired through the inhalation route. We stress the risk of transmission of the disease through the respiratory route from infected animals and by person to person contagion.

[Epidemic Kaposi's sarcoma. Apropos of 14 cases]. / Sarcoma de Kaposi epidémico. A propósito de 14 casos.

The epidemic Kaposi's sarcoma is the most common AIDS associated cancer. The lesions are located in any part of the organism. The skin affection is the most frequent. The risk group with a highest incidence is the "male homosexuals". Though the diagnosis of Kaposi's sarcoma doesn't determine "per se" the prognosis "quad vitam", there exist some analytic parameters at the time of the diagnosis that are useful for the prognosis of the HIV infection. We present 14 Kaposi's sarcoma and HIV infected cases analyzing some parameters and evaluating their prognosis and surviving hope.

[Pneumonia by Rhodococcus equi in patients with HIV infection]. / Neumonía por Rhodococcus equi en pacientes con infección por VIH.

We present the case of a patient with AIDS who developed abscessified pneumonia by Rhodococcus equi. We publish this case given the rare frequency of presentation of this opportunistic infection in this type of patient and given its good clinical evolution, on the contrary of other cases described so far in the literature. The good evolution of the patient may be due to an early diagnosis, less than one month, and the combined medical therapy with rifampicine and tetracyclines.

[Human immunodeficiency virus (HIV) infection. The effectiveness of different diagnostic sequences in suspected pulmonary infection]. / Infección por el virus de la inmunodeficiencia humana (VIH). Rentabilidad de diferentes secuencias diagnósticas ante sospecha de infección pulmonar.

BACKGROUND: Assessment of different diagnostic sequences, in patients VIH(+) with a suspected pulmonary infection. METHODS: A cross-sectional descriptive study of 76 HIV(+) patients with suspected respiratory infection. It has been determined the validity and the pretest and post-test probability of the radiology (Rx) of thorax, 67Ga pulmonary scintigraphy and seric LDH levels, in order to design four different diagnostic algorithms. RESULTS: The diagnostic sequence Rx-LDH-scintigraphy with normal results involved an infection probability of 58.0%. Pathological Rx with successively normal LDH and scintigraphy, implied a likelihood of 97.0%. The LDH elevation in sequence with scintigraphy and Rx rose to 96.1% if both were abnormal and diminished to 8.3% if normal. CONCLUSIONS: The LDH elevation associated with the sequence of normal Rx and scintigraphy suggests a low infection likelihood. On the contrary, associated with pathological Rx and scintigraphy in sequence, practically assures the pulmonary infection.