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Biomedical subjects

C Vidal

Publications and source records attributed to C Vidal.

At least 55 records · Page 3Linked to original sources
PubMed2000

Influence of acute alcohol intake and alcohol withdrawal on circulating levels of IL-6, IL-8, IL-10 and IL-12.

Cytokine balance alterations are responsible for some of the systemic and hepatic manifestations of alcoholism. The present study was aimed to evaluate the influence of both acute alcohol abstinence (in alcoholics) and acute alcohol intake (in healthy subjects) on serum IL-6, IL-8, IL-10, and IL-12 levels. Serum cytokine concentrations were determined on admission and after a median of 6 days of ethanol abstinence in 29 patients with alcohol withdrawal syndrome. The same determinations were made in five healthy volunteers at baseline and after 36 h of a single 60 g-dose alcohol intake. Increased serum levels of IL-6, IL-10 and, to a lesser extent IL-8, declined in the few days after alcohol abstinence in patients with alcohol withdrawal syndrome. Serum IL-8 values increased after alcohol intake in healthy subjects. Rapid variation of serum cytokine levels along with alcohol intake or abstinence should be taken into account in cytokine studies in alcohol abusers.

Adult↗
PubMed2000

Pharmacokinetics of SDZ RAD and cyclosporin including their metabolites in seven kidney graft patients after the first dose of SDZ RAD.

AIMS: The aim of the study was to investigate the pharmacokinetics and metabolism of the new immunosuppressant SDZ RAD during concomitant therapy with cyclosporin in stable renal transplant patients. Furthermore, we studied the influence of SDZ RAD on the pharmacokinetics of cyclosporin at steady state levels. METHODS: SDZ RAD was administered orally in different doses (0.25-15 mg day-1) to seven patients, who were on standard cyclosporin-based immunosuppression. The blood concentrations of both drugs including their main groups of metabolites were measured simultaneously by LC/electrospray-mass spectrometry. RESULTS: The mean area under the blood concentration-time curve to 12 h (AUC(0,12 h)) was 4244 +/- 1311 microg l-1 h for cyclosporin before SDZ RAD treatment and 4683 +/- 1174 microg l-1 h (P = 0.106) on the day of SDZ RAD treatment (95% CI for difference -126, 1003). On both study days Cmax, and tmax of cyclosporin were not significantly different. The metabolite pattern of cyclosporin did not change. The pharmacokinetic data of SDZ RAD dose-normalized to 1 mg SDZ RAD were as follows: AUC(0,24 h): 35.4 +/- 13.1 microg l-1 h, Cmax: 7.9 +/- 2.7 microg l-1 and tmax: 1.5 +/- 0.9 h. The metabolites of SDZ RAD found in blood were hydroxy-SDZ RAD, dihydroxy-SDZ RAD, demethyl-SDZ RAD, and a ring-opened form of SDZ RAD. CONCLUSIONS: A single dose of SDZ RAD did not influence significantly the pharmacokinetics of cyclosporin. The most important metabolite of SDZ RAD was the hydroxy-SDZ RAD, its AUC(0,24 h) being nearly half that of the parent compound SDZ RAD.

Administration, Oral↗
PubMed2000

Residual low-level viral replication could explain discrepancies between viral load and CD4+ cell response in human immunodeficiency virus-infected patients receiving antiretroviral therapy.

We report the evolution of chronic infection with human immunodeficiency virus type 1 (HIV-1) in a patient treated with stavudine plus didanosine, whose CD4+ lymphocyte count progressively decreased, despite a sustained plasma viral load <20 copies/mL. After 12 months of therapy, treatment was switched to zidovudine plus lamivudine plus nelfinavir. CD4+ T cell count decreased from 559 x 10(6)/L at month 0 to 259 x 10(6)/L at month 12. Plasma viral load decreased from 21,665 HIV-1 RNA copies/mL at baseline (month 0) to <20 copies/mL after 1 month of therapy with stavudine plus didanosine, and remained below 20 copies/mL until month 12, but always >5 copies/mL. Viral load in tonsilar tissue at month 12 was 125,000 copies/mg of tissue. After the change to triple-drug therapy, the plasma viral load decreased to 5 copies/mL, the CD4+ T cell count increased to 705 x 10(6)/L, and the viral load in tonsilar tissue decreased to <40 copies/mg of tissue at month 24. A low level of HIV-1 replication could explain the lack of immunologic response in patients with apparent virological response.

Adenoids↗
PubMed2000

[Vertigo, imbalance and mourning].

It is a well-known fact, and there are several publications on this matter, the links between panic attacks, simulation, anxiety, depression and lightheadedness or imbalance, but in our perusal of the related literature no connection between pathological mourning, dizziness and imbalance was found. In this paper are reported the outcomes of a prospective study of 58 patients suffering vertigo and imbalance as well and psychiatrically assessed. Pathologic mourning shows its predominance among otic vertiginous. This feature, we think, should be investigated when collecting the anamnesis of patients complaining of dizziness and/or imbalance in order to planning the appropriate treatment.

Grief↗
PubMed1999

Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replication.

OBJECTIVE: To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and their potential correlation with plasma viral load and central nervous system (CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T cell count >500x10(6) cells/l. PATIENTS AND METHODS: Consecutive patients screened for two trials were eligible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antibodies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain technique) and white cells were measured. RESULTS: The integrity of the blood-brain barrier was preserved (albumin index > or =7) in 59 out of 70 patients (84%). Intrathecal production of antibodies against HIV-1 p24 antigen was demonstrated in 55 out of 70 individuals (78%). Viral load in CSF was significantly lower than plasma values (3.13+/-0.95 versus 4.53+/-0.53, P = 0.0001). HIV-1 RNA was not detected in CSF in only three of the 70 patients (4%). Overall, there was a significant correlation between plasma and CSF HIV-1 RNA levels (r = 0.43, P = 0.0001); however, in 29 patients (41%) there were significant differences (>1.5 log10 copies/ml) between the viral loads in plasma and CSF. In the multivariate analysis, a high level of protein and white cells in CSF, but not the HIV-1 RNA plasma level, were factors independently associated with a higher level of HIV-1 RNA in CSF (P = 0.0001). CONCLUSIONS: HIV-1 RNA can be detected almost always in CSF of asymptomatic patients in early stages of HIV-1 infection including those with a preserved integrity of the blood-brain barrier. The important discrepancies between plasma and CSF viral load, and the independent association between CSF abnormalities and CSF viral load, support the hypothesis of local production of HIV-1.

Adult↗
PubMed1999

Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy.

BACKGROUND: This study addresses the dynamic of viral load rebound and immune system changes in a cohort of eight consecutive HIV-1-infected patients in very early stages [all the patients were taking highly active antiretroviral therapy (HAART} and were recruited in the coordinating center from a larger study] who decided to discontinue HAART after 1 year of treatment and effective virologic response. The safety of this procedure and the outcome with reintroduction of the same treatment was also investigated. METHODS: Plasma, cerebrospinal fluid (CSF), and lymphatic tissue viral loads were measured at baseline; lymphocyte immunophenotyping and CD4 lymphocyte proliferative responses to mitogens and specific antigens were assessed. The same antiretroviral therapy was reintroduced as soon as plasma viral load became detectable (above 200 copies/ml). RESULTS: At day 0, plasma viral load was below 20 copies/ml in all eight patients (and below 5 copies/ml in five of eight patients). A rebound in plasma viral load was detected in all patients from day 3 to day 31 with a mean doubling time of 2.01 (SE 0.29) days. Three out of eight patients achieved a peak plasma viral load at least 0.5 log10 above baseline, pretreatment values. Mutations associated with resistance to reverse transcriptase or protease inhibitors were not detected. After 31 days off therapy, CD4 lymphocytes decreased [mean 45% (SE 4) to 37% (SE 3); P = 0.04], CD8+CD28+ lymphocytes decreased [mean 59% (SE 5) to 43% (SE 4); P = 0.03], and CD8+CD38+ lymphocytes increased [mean 55% (SE 3) to 66% (SE 4); P = 0.009]. Mean stimulation indices of lymphocytes treated with phytohemagglutinin (PHA) and CD3 decreased from day 0 to day 31 from 34% (SE 8) to 17% (SE 9) (P = 0.06) and from 24% (SE 8) to 5% (SE 2) (P = 0.02), respectively. These changes were mainly contributed by the group of five patients with plasma viral load below 5 copies/ml at day 0. Viral load dropped below 20 copies/ml in all patients after 1 month of restarting the same antiretroviral regimen. CONCLUSIONS: Discontinuation of HAART after 1 year of successful treatment is followed by a rapid rebound of viral load; this rapidly returns to undetectable levels following reintroduction of the same treatment. In patients with more effective control of virus replication (viremia below 5 copise/ml), discontinuation of treatment was associated with more severe impairment of immunologic parameters.

Adult↗
PubMed1999

Expression and detection of macrophage-tropic HIV-1 gp120 in the brain using conformation-dependent antibodies.

HIV-1 envelope proteins gp120 and gp41 are likely to play a role in the pathogenesis of HIV-associated neurocognitive disorders. While detection of gp120 in HIV-infected cell cultures is easy, it has not yet been possible to identify gp120 in human or animal brains in situ. The difficulty in detecting gp120 could be due to low expression levels of the protein, to the shedding of gp120 from infected macrophages/microglia, or to the use of inappropriate gp-specific antibodies. We addressed these questions by analyzing the subcellular localization, oligomeric structure, and shedding behavior of gp120 from a macrophage-tropic, CCR5-dependent primary isolate, BX08, expressed by a Semliki Forest virus replicon (SFVenvBX08) in vitro. We used the same SFV system injected in vivo into the rat brain in an attempt to detect gp120 in situ. Our results show that gp120/41 is expressed as monomers, dimers, and trimers in cell culture. Immunocytochemical analysis revealed that intracytoplasmic gp120 can be recognized by an anti-V3 antibody, whereas gp120 at the plasma membrane is detected exclusively by a conformation-dependent antibody. In the rat brain, the SFV vector allows gene expression in neurons from day 3 to day 9 after injection without any apparent brain damage nor reactive astrogliosis. In SFVenvBX08-infected neurons only conformation-dependent antibodies allowed gp120 labeling. These results suggest that previous difficulties in detecting gp120 in brain tissues may be due to the use of antibodies which were unable to recognize gp120 at the plasma membrane.

Animals↗
PubMed1999

Simultaneous on-line extraction and analysis of sirolimus (rapamycin) and ciclosporin in blood by liquid chromatography-electrospray mass spectrometry.

We developed a sensitive and specific semi-automated liquid chromatography-electrospray mass spectrometric (HPLC-ESI-MS) assay for the simultaneous quantification of sirolimus and ciclosporin in blood. Following a simple protein precipitation step, the supernatants were injected into the HPLC system and extracted on-line. After column switching, the analytes were backflushed from the extraction column onto the analytical narrow-bore column and eluted into the ESI-MS system. The assay was linear from 0.4 to 100 microg/l sirolimus and from 2 to 1500 microg/l ciclosporin. The mean recoveries of sirolimus and ciclosporin were 98 and 96%, respectively. The mean interday precision/accuracy was 8.6%/-4.8% for sirolimus and 9.3%/-2.9% for ciclosporin.

Chromatography, High Pressure Liquid↗
PubMed1999

Serum cytokines and increased total serum IgE in alcoholics.

BACKGROUND: It has been reported that total serum IgE is increased in alcohol abusers, but the mechanisms responsible are not known. Production of IgE depends on B-cell stimulation by both antigens and some cytokines, particularly IL-4 and IL-13. Chronic alcoholism and alcoholic liver disease are accompanied by changes in cytokine production. AIM OF THE STUDY: To evaluate if IgE increase in alcoholics could be associated to a ethanol-induced imbalance of the cytokine profile. PATIENTS AND METHODS: A total of 65 patients (53 males and 12 females, aged 47 +/- 12 years), admitted to the hospital because of ethanol abstinence symptoms entered the study. On admission, total serum IgE was measured by chemiluminescent EIA and serum IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, and interferon-gamma were measured by ELISA. Data were compared with those of 40 healthy control subjects. RESULTS: Serum IgE, IL-6, IL-8, IL-10, IL-12, and IL-13 were found to be high in alcoholic patients compared with healthy volunteers. Some parallelism was observed between serum IgE and both serum IL-10 and IL-13 were increased in alcoholics. CONCLUSIONS: Total serum IgE elevation in alcoholics with abstinence syndrome is accompanied by an increase of some type 2 cytokines. Ethanol-induced alterations in the cytokine profile may contribute to increased IgE levels in alcoholics.

Adult↗
PubMed1999

Nicotinic receptors in the rat prefrontal cortex: increase in glutamate release and facilitation of mediodorsal thalamo-cortical transmission.

The modulatory influence of nicotinic acetylcholine receptor (nAChRs) on thalamocortical transmission was characterized in the prelimbic area (PrL) of the rat prefrontal cortex. In the first experiment, rats received a unilateral excitotoxic lesion centred on the mediodorsal thalamic nucleus (MD), and were sacrificed 1 week later. The lesion resulted in a 40% reduction of 3H-nicotine autoradiographic labelling in the ipsilateral prefrontal cortex, particularly in areas that are innervated by the MD. Electrophysiological experiments were subsequently performed in non-lesioned anaesthetized animals, in order to study modulation of short- and long-latency responses of PrL neurons evoked by electrical stimulation of the MD. The short-latency responses result from activation of the MD-PrL pathway and are mediated via AMPA-type glutamatergic receptors, whereas the long-latency responses reflect activation of the recurrent collaterals of cortical pyramidal neurons, Iontophoretic application of nicotinic agonists (nicotine, DMPP) facilitated both types of response. Local application of the nAChR antagonists dihydro-beta-erythroidine, mecamylamine and methyllycaconitine, prevented both kinds of facilitation. Finally, intracerebral microdialysis experiments were performed in order to test for nicotinic modulation of extracellular glutamate concentrations in the PrL. Direct application of nicotine via the dialysis probe increased glutamate levels in a dose-dependent manner. This effect was blocked by local perfusion of dihydro-beta-erythroidine. These findings therefore provide anatomical and functional evidence for nAChR-mediated modulation of thalamocortical input to the prefrontal cortex. Such a mechanism may be relevant to the cognitive effects of nicotine and nicotinic antagonists.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

Seroprevalence of Chlamydia pneumoniae in Chile.

We used microimmunofluorescence to survey the prevalence of antibodies to Chlamydia pneumoniae in 403 serum samples from asymptomatic subjects aged 6 months to 89 y in Santiago, Chile. The results suggest that Chlamydia pneumoniae infection is endemic in Chile, with a seroprevalence of 60% which does not differ by gender.

Adult↗
PubMed1999

LC/ESI-MS allows simultaneous and specific quantification of SDZ RAD and cyclosporine, including groups of their metabolites in human blood.

An analytic technique using liquid chromatography (LC) coupled with electrospray-mass spectrometry (ESI-MS) has been developed for the simultaneous determination of the new immunosuppressant SDZ RAD (40-O-[2-hydroxy)ethylrapamycin) and cyclosporine (Cs), including their metabolites in blood. With the time-sparing, automated on-line extraction technique, the recovery of SDZ RAD averaged 95% and that of Cs, 94%. The calibration lines were linear from 0.5 to 100 microg/L (r2 = 0.99) for SDZ RAD and from 10 to 1,000 microg/L (r2 = 0.99) for Cs. The method has been tested on blood samples from renal transplant recipients taken between 1 and 5 hours after oral SDZ RAD and Cs administration. In blood, we found the following metabolites: Hydroxy-SDZ RAD, dihydroxy-SDZ RAD, demethyl-SDZ RAD, and the ring-opened form of SDZ RAD. The main metabolite of SDZ RAD in blood was hydroxy-SDZ RAD. This novel LC/ESI-MS technique provided an excellent method for simultaneous quantitative monitoring of SDZ RAD and Cs, including their relevant groups of metabolites in patients treated simultaneously with these immunosuppressants.

Chromatography, High Pressure Liquid↗
PubMed1998

Predictive factors influencing peak viral load drop in response to nucleoside reverse transcriptase inhibitors in antiretroviral-naive HIV-1-infected patients.

Therapy with two nucleoside reverse transcriptase inhibitors (NRTI), the backbone of triple combinations, is still widely used in early stages of HIV-1 disease. However, factors influencing virologic response need to be further analyzed, to test the hypothesis that the reduction of plasma RNA viremia with NRTI may be greater in patients with higher baseline viral load (BVL) and to analyze the predictive factors of viral load drop below detection (200 HIV RNA copies/ml of plasma). Selected for the study were 169 HIV-1-infected antiretroviral therapy-naive patients with CD4+ T-lymphocyte counts ranging from 6 to 1040/microl coming from three randomized studies comparing the efficacy of monotherapy (zidovudine [ZDV], 250 mg every 12 hours; N=40) versus two-drug therapy consisting of ZDV (250 mg every 12 hours) with dideoxycytidine (ddC, 0.75 mg every 8 hours) or didanosine (ddI, 200 mg every 12 hours; N=129). Viral load was measured at 1, 3, and 6 months by polymerase chain reaction (PCR). A linear regression model was used to analyze the relation between BVL and the peak reduction of plasma RNA viremia. The variables included in a logistic regression model to determine the likelihood of VLs dropping below detection levels were age, gender, risk group for HIV-1 infection, baseline CD4+ lymphocyte count, BVL, clinical status (AIDS versus non-AIDS), HIV-1 phenotype (syncytium-inducing [SI] versus non-syncytium-inducing [NSI]) and type of treatment (monotherapy versus double therapy). The peak reduction of VL was related to baseline level following a linear model in both monotherapy and double-therapy regimens. In the subgroup of patients treated with two NRTIs, the regression line that fitted best with the data was log10 (peak reduction)=1.8-0.36 log10 (BVL) (F=23.5; p < .0001). This indicates that for every increase of 1 log10 of BVL, the peak reduction would be of 0.64 log10 greater. Forty-nine (29%) of the 169 patients dropped to <200 copies/ml. The likelihood of dropping below detection level was significantly greater in those receiving double therapy versus monotherapy (odds ratio [OR]=16.1; 95% confidence interval [CI], 2-128), in those with baseline CD4+ lymphocyte count >350/microl (OR=2.28; 95% CI, 1.1-4.9) and in those with BVL <10,000 HIV-1 RNA copies/ml (OR= 2.25; 95% CI, 1.1-6.1). None of the 13 patients with an SI phenotype at baseline dropped below detection levels. The reduction of VL in response to two NRTIs was greater in those patients with a higher level of BVL. In conclusion, peak reduction below detection in response to NRTI can be predicted and is associated with double therapy, with a baseline CD4+ cell count >350/microl and with a BVL <10,000 RNA copies/ml.

Adult↗
PubMed1998

Lack of evidence of a stable viral load set-point in early stage asymptomatic patients with chronic HIV-1 infection.

OBJECTIVE: To address the question of whether individuals with chronic HIV-1 infection have a stable viral load set-point and to assess the influence of host and viral factors on the evolution of viral load in a subset of stable asymptomatic patients with a baseline viral load below 5000 copies/ml and CD4+ T-cell count above 500 x 10(6)/l. METHODS: Medical visits were performed at least every 6 months including routine blood analysis, viral load and CD4+ T-cell count. HIV-1 RNA was measured in frozen (-70 degrees C) plasma samples using PCR. Patients were classified into three groups according to baseline viral load: group A, < 200 copies/ml (undetectable); group B, 201-2000 copies/ml; group C, 2001-5000 copies/ml. A survival analysis and a Cox regression model were performed to assess the influence of viral and host factors in the increase of baseline viral load. The endpoint was the time to increase viral load to a stable level > 0.5 log10 copies/ml above baseline viral load in groups B and C and to a stable detectable viral load (> 200 copies/ml) in group A. RESULTS: A cohort of 114 patients with viral load below 5000 copies/ml was followed for a median of 12 months (6-42 months). Overall, 22 (19%) out of 114 patients had an increase > 0.5 log10 copies/ml of baseline viral load. Baseline viral load increased in two (5%) out of 37 patients in group A, four (12%) out of 33 patients in group B, and 16 (36%) out of 44 patients in group C (survival analysis, P<0.002). Patients of group C had a eightfold higher risk of increasing baseline viral load than patients in the other two groups pooled together (hazards ratio, 8.28; 95% confidence interval, 1.78-38; P = 0.006). Patients with an increase of viral load to the virological endpoint had a threefold higher risk of decreasing baseline CD4+ T-cell counts > 100 x 10(6)/I than patients with stable viral load (hazards ratio, 2.78; 95% confidence interval, 1.12-14; P = 0.03). CONCLUSIONS: In our cohort of chronically HIV-1-infected asymptomatic patients with a baseline viral load < 5000 copies/ml and CD4+ cell count > 500 x 10(6)/l, a true viral load set-point did not seem to exist. Patients with baseline viral load of 2000-5000 copies/ml had an eightfold higher risk of increasing the level of viral load than patients with a baseline viral load below 2000 copies/ml.

Adult↗
PubMed1998

DNA vaccination with HIV-1 expressing constructs elicits immune responses in humans.

Humoral and cellular immune responses have been produced by intramuscular vaccination with DNA plasmids expressing HIV-1 genes, suggesting possible immunotherapeutic and prophylactic value for these constructs. Vaccination with these constructs has decreased HIV-1 viral load in HIV-1-infected chimpanzees. In addition, naive (i.e. non-HIV-1-infected) chimpanzees were protected against a heterologous challenge with HIV-1. Ongoing phase I clinical trials show that therapeutic vaccinations indeed boost anti-HIV-1 immune responses in humans. A therapeutic phase I trial on humans with these constructs induced a good safety profile and also demonstrated an immunological potentiation. These findings indicate that further studies with these constructs in humans are warranted.

AIDS Vaccines↗