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Biomedical subjects

J A Pineda

Publications and source records attributed to J A Pineda.

At least 19 recordsLinked to original sources

Prevalence of genotypic resistance to nucleoside analogues in antiretroviral-naive and antiretroviral-experienced HIV-infected patients in Spain.

OBJECTIVE: To determine the prevalence of genotypic resistance to nucleoside analogues (NA) in a large group of HIV-infected individuals in Spain, some of whom had no previous treatment with antiretroviral drugs (antiretroviral-naive) and some of whom had such experience (antiretroviral-experienced). SETTING: Cross-sectional study in out-patient clinics in three reference hospitals for HIV/AIDS located in Barcelona, Madrid and Seville, Spain. PATIENTS AND METHODS: Primary mutant genotypes were examined in plasma HIV RNA collected from 150 antiretroviral-naive subjects, half in 1993 and the other half in 1997. Furthermore, drug resistance mutations were analysed in plasma collected from another 150 antiretroviral-experienced patients who had received 2 NA for longer than 1 year, either in sequence as monotherapy or as combination therapy. A line probe assay was used for recognizing mutations conferring resistance to zidovudine (ZDV), didanosine (ddI), zalcitabine (ddC), and lamivudine (3TC). A point-mutation nested-PCR assay was used for examining a codon 151 mutation associated with multiple drug resistance. RESULTS: One or more mutations associated with primary resistance to NA were seen in 10 antiretroviral-naive (13.3%) patients in 1993 and in nine (12%) in 1997. In all but two cases, they were associated with ZDV resistance. In contrast, all but six (96%) of the antiretroviral-experienced subjects harboured drug-resistant mutant viruses. The codon 184 mutation (associated with resistance to 3TC) was detected in 92% of patients treated with 3TC, but also in 18% of those treated with only ddI or ddC. The codon 215 mutation was found in 67.3% of patients who had been exposed to ZDV; the codon 69 mutation was found in 15% of patients treated with ddC; and the codon 74 mutation was found in only 7.2% of patients treated with ddI. Finally, the codon 151 multidrug resistant mutation was found in four (2.7%) of 150 patients with a long-term exposure to NA. CONCLUSIONS: Overall, the prevalence of drug-resistant HIV-1 genotypes was 12.7% in antiretroviral-naive patients, most of whom had ZDV-resistant mutants. There is no evidence of an increase during the last 5 years. However, multidrug-resistant HIV genotypes are currently circulating in Spain.

Adult

Short-term evolution of HIV-1 viraemia and CD4+ cell counts in patients who have a primary mutation to zidovudine.

OBJECTIVE: To investigate the different responses to antiretroviral treatment including zidovudine, of patients harbouring HIV with primary resistance to zidovudine, serum viral load, and CD4+ cell counts, for 24 weeks in a group of antiretroviral-naive patients with the codon 215 mutation of the HIV pol gene and in a control group at the start of treatment. DESIGN: A case-control retrospective study (1989-1996). METHOD: Nineteen out of 210 patients previously studied harboured the codon 215 mutation, had a self-reported compliance with treatment, a minimum follow-up of 24 weeks, and were treated with zidovudine alone or in combination with other nucleoside analogues. These patients were matched with 19 patients with wild-type strains at entry by initial CD4+ cell counts, clinical status, and antiretroviral treatment. RESULTS: During the first 12 weeks, CD4+ cell counts increased (76+/-26 and 64+/-26 x 10(6)/l in wild-type and mutant virus-infected groups, respectively), decreasing slightly until week 24, although no significant differences were found between the two groups studied. Serum viral load decreased in both groups (change in serum viral load of 0.80+/-0.11 log10 and 0.87+/-0.26 log10 copies/ml, wild-type and mutant virus-infected, respectively), although no significant differences were found between groups. CONCLUSION: No significant differences were found between patients with the primary mutation to zidovudine and control patients harbouring wild-type virus in terms of short-term response measured by serum viral load and CD4+ cell counts.

Adult

[Impact of medical approach on the presentation form of AIDS defined by clinical episodes].

BACKGROUND: In recent years there has been a change in the opportunistic diseases incidence in HIV-infected patients. The change could be related to the use antiviral therapy and chemoprophylaxis strategies. The aim of the present study was to evaluate if medical intervention is able to modificate the clinical presentation of AIDS and the CD4+ lymphocyte counts at time of AIDS diagnosis. PATIENTS AND METHODS: The first AIDS-defining condition and the CD4+ count at time of AIDS diagnosis were analyzed in 95 HIV-infected patients who developed an AIDS-defining disease since April 1989 until March 1996, retrospectively reviewed. Patients who had been previously followed at an AIDS Unit were compared with those who had not. RESULTS: The frequency of Pneumocystis carinii pneumonia as the first AIDS-defining condition was lower in medically followed patients. Among this group, AIDS cases who received chemoprophylaxis with isoniazide showed a decrease in the rate of tuberculosis. No differences were found in CD4+ lymphocyte counts between both groups. CONCLUSIONS: As a result of medical intervention significant changes have occurred in the spectrum of initial AIDS-defining conditions in relation to medical intervention; a decrease in the frequency of Pneumocystis carinii pneumonia and tuberculosis have been found; however, the CD4+ lymphocyte counts at time of AIDS diagnosis are not modificated by medical intervention.

AIDS-Related Opportunistic Infections

Influence of hepatitis C virus infection on the mortality of antiretroviral-treated patients with HIV disease.

The aims of this study were to analyze the mortality directly attributable to chronic viral hepatitis in HIV-1 infected patients and to investigate the influence of hepatitis virus infections on the survival of this population. A cohort of 328 HIV-1 infected, antiretroviral-treated patients, followed up from 1989 to 1996, was investigated in the study. The median follow-up period of the cohort was 120 weeks. The median baseline CD4 + cell count of the cohort was 303 cells/mm3. Hepatitis C virus, hepatitis B virus and hepatitis D virus infections were present in 214 (65%), 16 (4.9%) and 9 (2.7%) patients, respectively. Sixty-seven (20.4%) subjects died but there was no information on the vital status of 36 patients (11%). The causes of mortality were AIDS in 49 (73%), liver failure in 3 (4.5%) and other causes in 15 (22.4%). The cohort was divided into two groups for survival analysis, the groups consisting of persons infected by a hepatitis virus and persons without hepatitis virus infection. There was no difference in survival between the two groups (p = 0.31, log-rank). It is concluded that mortality among HIV-1/hepatitis virus coinfected patients with moderate to severe immunosuppression is mostly due to AIDS, and that the survival of these subjects is not influenced by the presence of hepatitis virus infections, particularly hepatitis C virus.

Adult

Effects of cigarette smoking and 12-h abstention on working memory during a serial-probe recognition task.

Nicotine has been shown to affect attentional and mnemonic processes. However, whether these effects are due to changes in perceptual and/or motor aspects of the tasks is not at all clear. This study tested the hypothesis that nicotine from cigarette smoking has differential effects on perceptual and motor processes, as reflected by event-related potentials (ERPs) and reaction times (RTs), respectively, and that perceptual effects may be specific to changes in working memory. ERPs. RTs and performance accuracy were recorded from smokers and nonsmokers during a serial-probe recognition memory task in which lists of words or "memory sets" were followed by a probe word that was either in-set or out-of-set. Smokers were tested in a "smoking" and a 12-h "deprived" condition. Smoking-smokers and deprived-smokers exhibited fast RTs to in-set and out-of-set probes relative to a group of nonsmokers. They exhibited even faster RTs when the inset probe word matched the first or last item in the memory set. Thus, smokers as a group showed enhanced primacy and recency effects suggesting that smoking specifically facilitates processes related to the motor output aspects of working memory. Different effects characterized the electrophysiology. Larger P300s were recorded to in-set compared to out-of-set probes by both subject groups. Smoking smokers exhibited enhanced P300s to both types of probes. When smokers abstained for 12 h (deprived smokers), the differences in P300 amplitude were reduced but not eliminated. Smoking smokers exhibited faster P300 latencies to in-set probes, while deprived smokers showed delayed latencies relative to nonsmokers. Primacy and recency P300 effects characterized nonsmokers and deprived smokers. However, this relationship was reversed in the Smoking condition. These results support the hypotheses that nicotine has distinct effects on memory-related perceptual and motor aspects of working memory. The increase in efficiency of the memory search with nicotine is consistent with the functional role of the cholinergic system in maintaining a state "appropriate for efficient information processing."

Adolescent

Low sensitivity of peripheral blood smear for diagnosis of subclinical visceral leishmaniasis in human immunodeficiency virus type 1-infected patients.

The peripheral blood smear is an easy method for the diagnosis of symptomatic visceral leishmaniasis (VL) in human immunodeficiency virus type 1 (HIV-1)-infected patients. However, its efficiency in diagnosing subclinical VL remains unknown. In this study, Leishmania amastigotes were seen in blood smears from 1 of 13 HIV-1-positive individuals with subclinical VL. This shows that this procedure is not suitable for subclinical-VL diagnosis.

AIDS-Related Opportunistic Infections

Prevalence of and factors associated with visceral leishmaniasis in human immunodeficiency virus type 1-infected patients in southern Spain.

The actual prevalence of visceral leishmaniasis among human immunodeficiency type 1 (HIV-1)-infected patients in the Mediterranean basin remains unknown. There is also controversy about the risk factors for Leishmania infantum and HIV-1 coinfection. To appraise the prevalence of visceral leishmaniasis in patients infected with HIV-1 in southern Spain and to identify factors associated with this disease, 291 HIV-1 carriers underwent a bone marrow aspiration, regardless of their symptoms. Giemsa-stained samples were searched for Leishmania amastigotes. Thirty-two (11%) patients showed visceral leishmaniasis. Thirteen (41%) patients had subclinical cases of infection. Centers for Disease Control and Prevention (CDC) clinical category C was the factor most strongly associated with this disease (adjusted odds ratio [OR], 1.88 [95% confidence interval, 1.22 to 2.88]), but patients with subclinical cases of infection were found in all CDC categories. Female sex was negatively associated with visceral leishmaniasis (adjusted OR, 0.42 [95% confidence interval, 0.18 to 0.97]). Intravenous drug users showed a higher prevalence than the remaining patients (13.3 versus 4.9%; P = 0.04), but such an association was not independent. These results show that visceral leishmaniasis is a very prevalent disease among HIV-1-infected patients in southern Spain, with a high proportion of cases being subclinical. Like other opportunistic infections, subclinical visceral leishmaniasis can be found at any stage of HIV-1 infection, but symptomatic cases of infection appear mainly when a deep immunosuppression is present. There is also an association of this disease with male sex and intravenous drug use.

AIDS-Related Opportunistic Infections

Human and monkey P3-like responses in a mixed modality paradigm: effects of context and context-dependent noradrenergic influences.

Previous studies in non-human primates have reported that noradrenergic agents, such as the alpha 2 agonist clonidine, affect auditory but not visual P3 responses. One explanation for these effects may be that distinct modalities are differentially susceptible to noradrenergic influences--a modality-dependent effect. Another possibility is that noradrenergic effects are modality-independent but context-dependent. Two separate experiments, in humans and monkeys, examined the role of stimulus modality, context and noradrenergic activity in an attempt to elucidate the nature of the relationship between P3 and the action of this catecholamine neurotransmitter. In Experiment 1, human subjects were exposed to two versions of a mixed modality oddball paradigm. In one version, the context or background activity was auditory, while in the other it was visual. In both versions of the paradigm, the same auditory and visual rare targets occurred. The results indicated that N2 and P3 to visual targets were more sensitive to changes in context than those to auditory targets. In both cases, N2 and P3 amplitudes to targets were enhanced when the eliciting event and context differed. A modality-specific N2b, on the other hand, was enhanced when the context matched the modality of the eliciting event. In Experiment 2, monkeys received systemic injections of a saline placebo or one of three doses of the adrenergic antagonist L657,743 prior to presentation of a mixed modality oddball paradigm in a visual context. Drug effects were observed on earlier components such as N1, P2 and N2 but not on later P3-like responses. The combined findings complement previous ones from our laboratory and suggest that P3 reflects context-dependent processes and specifically context-dependent, not modality-specific, noradrenergic activity.

Adrenergic alpha-Antagonists

Unexpected high prevalence of hepatitis C virus genotype 4 in Southern Spain.

BACKGROUND/AIMS: A unusually high rate of HCV-infected individuals in whom the HCV genotype cannot be ascertained by means of single PCR and LIPA procedures has recently been reported in our area. The aim of the present study was to investigate the epidemiological, clinical and molecular characteristics of these patients. METHODS: Cross-sectional study. Eighty anti-HCV-positive patients with chronic liver disease, 45 (56.25%) of them intravenous drug users, were included. HCV genotyping was carried out in all patients using commercial single PCR and LIPA procedures. Samples where no HCV RNA amplification and/or indeterminate HCV genotype were found were also tested by means of a nested PCR. HCV viral load was measured in all patients. RESULTS: HCV genotyping was not achieved in 23 (28.75%) individuals. No amplification of HCV RNA was found in 19 of them, and in four other cases the LIPA procedure did not allow identification of a distinct HCV genotype. After the use of nested PCR+LIPA, it was found that the HCV genotype 4 was found in 11 of those 23 individuals (47.82%). Ten of these 11 HCV genotype 4-harboring individuals were intravenous drug users. The HCV viral load was lower in HCV genotype 4-harboring individuals than in those whom the genotypes 1, 2 or 3 were found (p<0.001). CONCLUSIONS: A high rate of HCV genotype 4-harboring cases has been found among HCV-infected individuals in Southern Spain. Had only single PCR been used, these individuals could have been wrongly regarded as non-viremic.

Chronic Disease

[A cystic lymphoepithelial lesion of the parotid in HIV-1-infected patients].

Cystic lymphoepithelial lesion is an infrequent disorder involving the saliva glands mainly the parotid gland; however, its frequency has increased coinciding with the epidemics of HIV-1 infection. Three cases of parotid lymphoepithelial lesion in patients with HIV-1 infection, 2 of whom were hemophiliacs and one an ex-intravenous drug addict, are presented. In all the cases the lesion was a painless slow growth right submandibular mass, with no history of inflammation. Two of the patients had a contralateral tumor of the same characteristics which was not studied. Fine needle aspiration puncture was performed in the three patients although diagnosis was obtained by pathologic study following superficial parotidectomy. Cystic lymphoepithelial lesion is an entity to be taken into account on differential diagnosis of cervical masses in patients with HIV infection. In individuals with severe immunosuppression treatment should be conservative.

Acute Disease