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Biomedical subjects

A Muñoz

Publications and source records attributed to A Muñoz.

At least 19 recordsLinked to original sources

Evolution of biological effects of Aznalcóllar mining spill in the Algerian mouse (Mus spretus) using biochemical biomarkers.

The status of Guadiamar stream, polluted in 1998 by metals spilled from a pyrite tailings dam, was monitored from 1999 to 2001 to assess possible biological effects in terrestrial ecosystems of Doñana National Park (DNP) (Andalusia, SW Spain). The Algerian mouse (Mus spretus) was used as bioindicator at different Guadiamar and Doñana sites. Eleven biochemical parameters, including the activities of antioxidative and biotransforming enzymes and oxidative damages to biomolecules, were assayed in liver as biomarkers responsive to metals and organic pollutants. In 2001, metals were also determined in kidney and their possible correlation with biomarker responses was studied. Contents of Pb, Cd and As significantly correlated with several antioxidative enzymes. Biomarkers responsive to oxidative stress indicate the presence of transition metals in the high and medium Guadiamar course, and their response diminished with the distance to the collapsed dam. The high ethoxyresorufin-O-deethylase (EROD) activity of mice from the medium and low Guadiamar course point to organic pollutants, such as the pesticides used in intensive crops grown in areas nearby Doñana. The increasing responses of several biomarkers at reference sites may suggest a progressive pollution of key Doñana ecosystems.

Animals↗

Fraction of cases of acquired immunodeficiency syndrome prevented by the interactions of identified restriction gene variants.

Previous research has demonstrated isolated effects of host genetic factors on the progression of human immunodeficiency virus type 1 (HIV-1) infection. In this paper, the authors present a novel use of multivariable methods for estimating the prevented fraction of acquired immunodeficiency syndrome (AIDS) cases attributable to six restriction genes after accounting for their epidemiologic interactions. The methods presented will never yield a prevented fraction above 1. The study population consisted of a well-characterized cohort of 525 US men with HIV-1 seroconversion documented during follow-up (1984-1996). On the basis of a regression tree approach using a Cox proportional hazards model for times to clinical AIDS, the combinations of genes associated with the greatest protection, relative to the lack of a protective genotype, consisted of: 1) C-C chemokine receptor 5 (CCR5)-Delta 32 and C-C chemokine receptor 2 (CCR2)-64I (relative hazard = 0.44); 2) interleukin 10 (IL10)-+/+ in combination with CCR5-Delta 32 or CCR2-64I (relative hazard = 0.45); and 3) IL10-+/+ in combination with stromal-derived factor (SDF1)-3 'A and CCR5 promoter P1/approximately P1 (relative hazard = 0.37). Overall, 30% of potential AIDS cases were prevented by the observed combinations of restriction genes (95% confidence interval: 7, 47). However, the combined effect was confined to the first 4 years following HIV-1 seroconversion. Additional research is needed to identify AIDS restriction genes with stronger and long-lasting protection to better characterize the genetic epidemiology of HIV-1.

Acquired Immunodeficiency Syndrome↗

[Brainstem gliomas].

Brainstem gliomas have been increasingly understood in the last two decades and they are nowadays regarded as an heterogeneous group of tumors with tendency towards the pediatric age, where they account for 10-20% of brain neoplasms. Besides the well known diffuse tumor, several subtypes, with a different biological behaviour, amenable to surgical resection and better prognosis, have been identified, giving rise to many classifications and terms. In the other way, attention has been recently paid to adult brainstem gliomas in contrast to pediatric tumors. Based on a review of the literature, we describe the different subtypes of brainstem gliomas, with particular interest on therapeutic approaches and differences between pediatric and adult tumors, employing iconography from our series.

Adult↗

Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus.

Impairment of GABA-mediated inhibition is one of the main hypotheses invoked to explain seizure activity, both in experimental models and in human epilepsy. We have studied the distribution and the neurochemical characteristics of certain GABAergic circuits in the normal and epileptic human sclerotic hippocampal formation. We have focused our attention mainly on chandelier cells because, together with basket cells, they are considered to have powerful effects on spike generation. Chandelier cells represent a unique type of interneuron whose axon terminals (Ch-terminals) form synapses with the axon initial segments of cortical pyramidal cells and granular cells of the dentate gyrus. Different neurochemical subpopulations of chandelier cells have been identified by immunocytochemistry, mainly in the neocortex. Markers for Ch-terminals include the GABA transporter 1 (GAT-1), the polysialylated form of the cell-surface glycoprotein neural cell adhesion molecule (PSA-NCAM) and the calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB). In the normal hippocampal formation, GAT-1- and PV-immunoreactive (-ir) Ch-terminals were identified in the granular and polymorphic layers of the dentate gyrus, in the strata pyramidale and oriens of the CA fields, and in the pyramidal layer of the subicular complex. In addition, and in contrast to the hippocampus and dentate gyrus, subsets of Ch-terminals in the upper pyramidal layer of the normal subiculum express CB and PSA-NCAM. The sclerotic hippocampus of epileptic patients presented an impressive morphological and neurochemical reorganization of Ch-terminals and basket formations. This was apparent in the dentate gyrus and hippocampal formation, but not in the subiculum, which appeared to remain unaltered. Principally, numerous and more complex PV- and CB-ir Ch-terminals, as well as dense PV-ir basket formations, appeared in some hippocampal segments, whereas in other regions there was a lack of labelled elements. These changes varied considerably not only between different patients, but also within different hippocampal fields in a given patient. In general, the changes were not correlated with the clinical characteristics or degree of histopathological alterations observed in the patients, such as granular cell dispersion, neuron loss and proliferation of mossy fibres. However, some surviving neurons in the regions adjacent to the areas of neuron loss were consistently innervated by dense basket formations and complex Ch-terminals. These results indicate that, in the human epileptic hippocampus, GABAergic circuits are more highly modified than previously thought. When considered along with other extrahippocampal alterations, we suggest that these changes are important in the pathophysiology of temporal lobe epilepsy associated with hippocampal sclerosis.

Adolescent↗

Interaction between the noradrenergic and serotonergic systems in locomotor hyperactivity and striatal expression of Fos induced by amphetamine in rats.

It is classically considered that Amphetamine acts by increasing extracellular dopamine levels. However, some data suggest a relevant role of other neurochemical systems. The striatum is of particular interest to the study of this question. We have investigated the involvement of the noradrenergic and serotonergic systems and their possible interaction in the striatal responses to Amphetamine using a double behavioral and immunohistochemical approach (i.e., changes in locomotor activity and striatal expression of Fos). In normal rats, Amphetamine induced locomotor hyperactivity and striatal expression of Fos. Pretreatment with the alpha1-adrenergic-receptor antagonist Prazosin or lesion of the serotonergic system significantly reduced the locomotor hyperactivity and striatal Fos expression induced by Amphetamine. Administration of Prazosin to rats with serotonergic denervation did not produce any further reduction in the Amphetamine-induced locomotor hyperactivity or striatal Fos expression compared with that observed in rats with serotonergic denervation only. Amphetamine did not induce a detectable increase in Fos expression in dopamine-denervated striata, and elicited intense rotation towards the dopamine-denervated side. This suggests that striatal dopamine release is essential in the Amphetamine-induced effects on striatal neurons. However, the noradrenergic system plays an important role, and the serotonergic system is necessary for mediating the effects of the Amphetamine-induced noradrenergic stimulation. Concurrent stimulation of dopaminergic and serotonergic receptors appears necessary to regulate Amphetamine-induced responses in the striatal neurons.

Adrenergic alpha-Antagonists↗

NMR studies of phenylbenzohydroxamic acid and kinetics of complex formation with nickel(II).

The behavior of N-phenylbenzohydroxamic acid (PBHA) in organic solvents has been investigated by (1)H and (13)C NMR spectroscopy. Measurements in acetone at different temperatures and concentrations enable one to individualized two signals, in a 20/80 area ratio, which were ascribed to partition of PBHA between two isomers, HZ (cis) and HE (trans). The dependence of the low-intensity peak on concentration and temperature strongly suggests dimer formation. Since only the HZ form can give dimers, it may be concluded that in acetone PBHA is present mainly in the HE form. (13)C NMR measurements in methanol yielded a 50/50 [HZ]/[HE] ratio. The equilibria and kinetics of complex formation in aqueous solutions between Ni(II) and PBHA were investigated by spectrophotometric and stopped-flow techniques at 25 degrees C and 0.2 M ionic strength. Two reaction paths, involving the binding of Ni(2+) to the neutral PBHA and to its anion, were observed. The rate constants of the forward and reverse steps are k(1) = (7.1 +/- 0.3) x 10(2) M(-)(1) s(-)(1) and k(-1) = (4.9 +/- 0.6) s(-)(1) for the step involving the undissociated PBHA and k(2) = (5.5 +/- 0.7) x 10(4) M(-)(1) s(-)(1) and k(-2) = (1.2 +/- 0.1) s(-)(1) for the step involving the anion. The k(2) value indicates that the PBHA anion reacts with Ni(2+) according to Eigen's mechanism and that in water the cis form prevails. The k(1) value is lower by a factor of 13 compared to the value estimated on the basis of Eigen's mechanism, suggesting that at least 90% of the neutral ligand is present in a nonreactive conformation.

Journal Article↗

Fronto-orbital remodeling without orbito-naso-frontal bandeau.

INTRODUCTION: Fronto-orbital bilateral advance is the procedure of choice for the treatment of craniosynostosis affecting most of the anterior area of the skull and orbitomalar regions. The aim of the technique is to achieve a supra-orbital bilateral bar and a frontal bone. We have introduced a modification in order to simplify the technique. PATIENTS AND METHODS: From November 1998 to January 2002, 18 patients with craniosynostosis have been surgically treated using our technique. The mean age when the treatment was performed was 6.93 months (range 3 to 22 months). Brain computed tomography (CT) scans and three-dimensional (3-D) reconstruction of CT scans were performed before and after treatment. SURGICAL TECHNIQUE: A bifrontal craniotomy was performed taking the osteotomy up to the supraorbital rim. A new frontal bone was obtained from another region of the cranium creating new orbital edges. The osteosynthesis was conducted using absorbable materials. RESULTS: The follow-up of the patients ranged from 3 months to 3 years. All patients were studied using CT scans and 3-D reconstruction of CT after treatment, which demonstrated the persistence of the fronto-orbital advance. No secondary complications related to the new technique were found in any of the patients. CONCLUSIONS: The frontal-orbital advance obtained was stable. The technique was simplified by not creating a supraorbital bar and by reducing the bone fixation points. The manipulation of both frontal lobes and orbital globes was negligible. The aesthetic results were excellent.

Bone Remodeling↗

Immunopathology of an hDAF transgenic pig model liver xenotransplant into a primate.

BACKGROUND: hDAF transgenic pigs do not display the inherent hyperacute rejection reactions of pig-to-primate xenotransplants. The purpose of this study was to determine the immunopathologic phenomena following an hDAF transgenic pig hepatic orthotopic xenotransplant into a baboon. METHODS: Donor animals were unmodified pigs (n=4) and hDAF transgenic pigs (n=2). Recipient animals were baboons (Papio anubis). Liver biopsies were immunostained using monoclonal antibodies to C3, C5b-9, IgG, IgM, CD2, CD4, CD8, CD68, CD20, Bric 216, CD31, and fibrin, and polyclonal antibody to C4. RESULTS: hDAF transgenic grafts showed IgG, IgM, and C4 endothelial deposits. However, no fibrin, C3, or C5b9 deposits were observed after reperfusion. hDAF xenografts displayed CD31 staining in the portal spaces, perilobular areas, and at hepatic sinuisoidal levels. The baboon that lived for 4 days displayed either CD4 or CD8 T-cells periportal infiltrate. CONCLUSIONS: Future studies will seek to determine the physiologic role of CD31 hepatic sinusoidal expression in transgenic xenotransplants, and will also study the role of T-cell infiltrates in xenograft rejection.

Animals↗

[Steady car engine noise does not affect the cognitive abilities of sleep apnea syndrome patients].

Traffic accidents are more frequent for sleep apnea syndrome (SAS) patients than in the population at large. The mechanisms that underlie this observation are poorly defined. Our working hypothesis was that in SAS patients the steady noise of a car engine might alter cognitive capacities that may be involved in driving, thus increasing the risk of traffic accidents. To test this hypothesis we designed a prospective randomized controlled trial. Eighteen SAS patients (apnea-hypopnea index [SEM] 62 [6] h1) and 18 healthy controls were studied. All the participants were evaluated in random order both in basal conditions and after exposure to the steady noise of a car engine recorded on a compact disc. Their level of vigilance was evaluated (Steer-Clear) as well as their reaction time (PVT 192). Attention, coordination, and memory were measured using the following tests: Wechsler Memory Scale (digit span), the Wechsler Intelligence Scale (digit symbol), and Lezack's Trail Making tests A and B. The SAS patients were slightly younger than the control group (mean 50 [7] vs 57 [11] years, respectively; P=.05). The patients showed a lower level of vigilance than the controls both in basal and engine noise conditions (P<.05). No differences between groups were found for the other variables studied. Exposure to steady car engine noise had no effect on the tests of either group. In conclusion, the results of our study do not support the hypothesis that steady car engine noise significantly alters the cognitive ability of SAS patients.

Accidents, Traffic↗

Localization of KCNQ5 in the normal and epileptic human temporal neocortex and hippocampal formation.

The KCNQ family of voltage-dependent non-inactivating K+ channels is composed of five members, four of which (KCNQ2-5) are expressed in the CNS and are responsible for the M-current. Mutations in either KCNQ2 or KCNQ3 lead to a hereditary form of dominant generalized epilepsy. Using specific antisera to the KCNQ2, KCNQ3 and KCNQ5 subunits, we found that KCNQ3 co-immunoprecipitated with KCNQ2 and KCNQ5 subunits, but no association was detected between KCNQ2 and KCNQ5. Intense KCNQ5 immunoreactivity was found to be widely distributed throughout the temporal neocortex and the hippocampal formation. In these structures, both pyramidal and non-pyramidal neurons and a population of glial cells in the white matter expressed the KCNQ5 subunit. In the sclerotic areas of the CA fields of epileptic patients, a marked loss of KCNQ5 immunoreactive pyramidal neurons was found in relation with the loss of neurons in these regions. However, in the regions adjacent to the sclerotic areas, the distribution and intensity of KCNQ5 immunostaining was apparently normal. The widespread distribution of KCNQ5 subunits, its persistence in pharmacoresistant epilepsy, along with the significant role of the M-current in the control of neuronal excitability, makes this protein a possible target for the development of anticonvulsant drugs.

Adolescent↗

[Analysis of cerebrospinal fluid related complications (hydrocephalus, fistula, pseudomeningocele and infection) following surgery for posterior fossa tumors].

INTRODUCTION: Hydrocephalus, cerebrospinal fluid (CSF) leak, pseudomeningocele and CSF infection are potential complications related to surgical treatment of posterior fossa tumors. The objectives of this study were to review the incidence of such complications and to identify contributing factors related to them. MATERIAL AND METHODS: This study is based on a retrospective review of the medical records of 71 consecutive patients who underwent posterior fossa surgery for a tumor between the period January 1997 and December 2001. Postoperative hydrocephalus was defined as enlargement of the ventricles and the subsequent clinical worsening requiring surgical treatment. Criteria for CSF leakage were:observed leak of CSF through the wound, rhinorrhea or otorrhea. Pseudomeningocele was determined when there was a large epidural CSF collection diagnosed in the postoperative period or by magnetic resonance imaging performed at least three months after posterior fossa surgery. Finally, CSF infection was defined on clinical ground and positive biochemical examination, but not necessarily positive cultures. RESULTS: The series included 84 operations for resection of posterior fossa tumors on 71 patients. There were CSF related complications in 31% (26/84)with the following detailed incidence: 9.5% (8/84) postoperative hydrocephalus; 14.3% (12/84) CSF leak, 7.1% (6/84) pseudomeningocele; 8.3% (7/84) CSF infection. The mortality rate is 5.9% (5/84). The tumor size was the only statistically significant factor associated with the occurrence of CSF related complications (mean 39.43 mm, SD 18.51 mm vs.29.80 mm, SD 14.12 mm, p=0.015). In the subgroup of patients, in which hydrocephalus was managed preoperatively, the election of an external ventricular drain vs.other strategies (subcutaneous reservoir, definite shunt or endoscopic third ventriculostomy) was associated with a higher occurrence of CSF related complications (p=0.006). The mortality rate was associated with age (mean 63.60 years, SD 5.86 years vs.49.18 years, SD 16.39 years; p=0.002). The occurrence of CSF related complications also influenced mortality (p=0.030), particularly postoperative hydrocephalus (p< 0.001). Inpatient hospital stay was longer in the subgroup of patients who developed CSF related complications (p=0.002). CONCLUSIONS: Tumor size was the only factor associated with the development of CSF related complications after surgery for posterior fossa tumors. In the subgroup of patients in which hydrocephalus was surgically treated preoperatively, the election of an external ventricular drain compared to other surgical modalities was associated with a higher rate of CSF related complications. The development of such complications, particularly hydrocephalus, was related with mortality.

Bacterial Infections↗

[Congenital brain tumors: nine cases and review of the literature].

OBJECTIVE: To review congenital brain tumors patients younger than 2 months diagnosed in our Department. PATIENTS AND METHODS: Nine congenital brain tumors were diagnosed between 1983 and 2001 among a consecutive serie of 484 paediatric cerebral tumors (patients less than 15 years). Clinical and radiological findings and prognostic factors are analyzed. RESULTS: There were two teratomas, two glioblastomas, one xanthogranuloma affecting cavernous sinus, one supratentorial PNET and one medulloblastoma and one oligodendroglioma. In one case histological diagnosis was not possible. In four cases antenatal diagnosis was done by means of ultrasonography and MRI. Seven patients were operated on, with one intraoperative exitus. Five patients died due to tumoral progression in the first two months after surgery. Another case was considered not amenable for surgical resection, and thus was not operated. He died in the fifth day of life. Three patients are alive 14, 36 and 72 months after surgery, one with severe psicomotor delay, another one with normal mental status but dependent on seizures medication and the last one with mild mental delay. In the last case of our serie intrauterine death happened by 33(rd )week and histological diagnosis was not possible. CONCLUSIONS: Prognosis for congenital brain tumors depends on the operative morbidity and tumor histology. However final prognosis in these patients is still discouraging, despite early surgery and operative and anaesthetic improvements.

Adult↗

Effects of asthma on cell components in peripheral blood among smokers and non-smokers.

BACKGROUND: Eosinophils play a central role in asthma, but the interplay of the effects of smoking, eosinophils and asthma remains unclear. OBJECTIVE: The primary objective of our study was to investigate the extent to which smoking modifies the effect of asthma on circulating eosinophils, CD4+ and CD8+ T cell counts. METHODS: Data were collected semiannually between 1987 and 1994 from HIV-negative participants in the Multicenter AIDS Cohort Study. Asthma was defined by a questionnaire at baseline as a self-report of diagnosed asthma. A total of 1420 blood samples from 197 asthmatics and 15 822 from 1997 non-asthmatics were collected. RESULTS: Eosinophil levels were higher in asthmatics (28% of asthmatics had eosinophils >/=4% and 16% of non-asthmatics) regardless of smoking history, but smoking modified the association between eosinophils and asthma. Namely, the odds ratios for eosinophils being >/=4% in asthmatics to non-asthmatics decreased from 2.7 (95% CI: 2.0, 3.6) in never, to 2.1 (1.4, 3.1) in former, and to 1.5 (0.9, 2.3) in current smokers. Cross-sectional and longitudinal analyses coherently showed that smoking increased eosinophils in non-asthmatics, but the converse was true for asthmatics. In contrast, no differences in peripheral blood T cell counts between asthmatics and non-asthmatics were observed. CONCLUSION: Under the established link between increased eosinophils and asthma, these data indicate that smoking modified this relationship. This finding suggests that smoking plays a different immunological role in asthmatics and non-asthmatics.

Adult↗

Lectin typing of five medically important Candida species.

This study reports the patterns of agglutination of 93 clinical Candida isolates by 14 commercial lectins. The isolates were of the species Candida albicans (55), C. tropicalis (12), C. guilliermondii (10). C. glabrata (eight) and C. parapsilosis (eight). Hundred percent of isolates were agglutinated, at least, by a panel of three lectins: Canavalia ensiformis (ConA), Lens culinaris (LCA) and Pisum sativum (PSA), all of them with alpha-D-mannose specificity. In addition, another panel of three lectins could distinguish between C. glabrata, C. tropicalis and C. albicans. Lectin typing may be of potential value for taxonomic and epidemiological studies of yeasts in clinical laboratories.

Agglutination↗

A novel biweekly schedule with cisplatin and gemcitabine in advanced non-small cell lung cancer.

A new schedule with cisplatin and gemcitabine administered biweekly was prospectively evaluated in stage IIIB or IV non-small cell lung cancer. We report the interim analysis of the safety and efficacy with the first 23 patients included. The mean age was 60. Thirteen patients (56.5%) were stage IIIB and 10 (43.5%) were stage IV The overall response rate was 47.8%: 69.2% for stage IIIB and 20% for stage IV The median survival among the 23 patients was 33 weeks and 1-year survival was 39%: 53.8% for stage IIIB and 20% for stage IV Seventy-seven cycles (154 administrations) were given. The mean number of cycles/patient was 3.3 (range: 1 to 6). Of the 154 administrations, 26 were delayed 1 week for recovery from toxicity. The dose intensity (Hryniuk criteria) was 94% of the planned dose. There was one toxic death with grade 4 thrombocytopenia and grade 4 esophagitis. In two patients, grade 3-4 vascular toxicity was observed, with distal arterial ischemic changes in the lower extremities. There were three (3.9%) episodes of grade 2 neutropenia, one (1.7%) of grade 3 and another one of grade 4. No cases of febrile neutropenia were seen. Predominant nonhematologic toxicities were asthenia and nausea/vomiting. This schedule of cisplatin and gemcitabine has a good therapeutic index and, as it is active, enrollment is ongoing to complete the second part of the study.

Adenocarcinoma↗

A case-control study of HIV-1-related dementia and co-infection with HHV-8.

This nested case-control study assessed the putative protective effect of human herpesvirus-8 (HHV-8) against HIV-1-related dementia (dementia). The HHV-8 seropositivity of 210 male age- and HIV disease stage-matched cases and controls was compared. The overall HHV-8 seropositivity of 66% was similar among demented HIV-infected cases and nondemented HIV-infected controls.

AIDS Dementia Complex↗

Evaluation of the effectiveness of highly active antiretroviral therapy in persons with human immunodeficiency virus using biomarker-based equivalence of disease progression.

The association of different CD4(+) cell counts with the same disease risk in treated and untreated populations reflects the effectiveness of highly active antiretroviral therapy (HAART) in persons with human immunodeficiency virus (HIV). Clinical progression of disease following initiation of HAART was determined for 679 HIV-infected men in the Multicenter AIDS Cohort Study by means of Kaplan-Meier survival analyses. Cox proportional hazards models were used to assess the effects of markers of HIV disease, antiretroviral history, and demographic factors. Men who had been followed since January 1993 (pre-HAART) were used to identify CD4(+) levels associated with the acquired immunodeficiency syndrome (AIDS)-free time equivalent to that of men starting HAART with CD4(+) cell counts of <200 cells/microl. Within 3.5 years following HAART initiation, 11.3% of the subjects developed AIDS and 8.5% died. Determinants of AIDS were a CD4(+) cell count of <200 cells/microl at initiation (relative hazard = 2.25, 95% confidence interval: 1.13, 4.49) and age >45 years at initiation (relative hazard = 1.92, 95% confidence interval: 0.98, 3.77). An increase in CD4(+) cell count of >50 cells/microl immediately after HAART initiation also improved prognosis (relative hazard = 0.34, 95% confidence interval: 0.16, 0.71). AIDS risk in men starting HAART with CD4(+) counts of <200 cells/microl (median = 132) was similar to that of non-HAART users with CD4(+) counts of 375-475 cells/microl (median = 432). The equivalence of disease progression to that of nonusers with approximately 300 more cells per microl demonstrates that HAART users have a broader reconstitution of the immune system beyond that of observed increases in CD4(+) cell count.

Acquired Immunodeficiency Syndrome↗