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Biomedical subjects

Javier Sanz

Publications and source records attributed to Javier Sanz.

At least 37 records · Page 2Linked to original sources
PubMed2005

Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia.

The effects of atypical antipsychotic treatment on the brain volume deficits associated with schizophrenia are poorly understood. We assessed the brain volumes of eleven healthy controls and 29 patients with schizophrenia, using magnetic resonance imaging at baseline and at follow-up after two years of treatment with atypical neuroleptics. Two groups of patients were analyzed: treatment-naïve patients (n = 17) and chronic treatment-resistant patients (n = 12). Treatment-naïve patients received risperidone during the follow-up period, whereas chronic patients received clozapine. Gray matter (GM) and white matter (WM) volumes in the frontal, parietal, occipital, and temporal lobes were measured. Contrary to the controls, both groups of patients presented GM increases and WM decreases in the parietal and occipital lobes (p < .005). Frontal GM also increased in the chronic group with clozapine. There was a significant (p < .001) inverse relationship between the baseline volumes (GM deficit/WM excess) and the longitudinal change. These GM and WM changes were not related to changes in weight. Thus, treatment with risperidone and clozapine in schizophrenia may have an effect on gray and white matter volume and needs further exploration.

Adult↗
PubMed2005

Dorsolateral prefrontal and superior temporal volume deficits in first-episode psychoses that evolve into schizophrenia.

Regions with a likely involvement in schizophrenia may differ between patients with first-episodes of psychosis respectively with and without evolution into schizophrenia following the initial episode. We have used magnetic resonance imaging (MRI) to assess the volumes of dorsolateral prefrontal (DLPF) and superior temporal gyrus (STG) in a group of 37 first-episode psychotic patients. After an initial MRI study performed by the time of the first episode, the subjects were followed for two years. After this period 22 cases were diagnosed with schizophrenia, while the other 15 did not show clinical evidence for this illness. A Talairach-based tool was used for segmentation and volumetry of the MRI scans. A group of 44 healthy controls was used for comparison and, using lineal regression, to control for the normal effects of age and intracranial volume on the regional parameters of the patients. By the time of their first episode, patients with schizophrenia had significantly less grey matter in the right DLPF and STG regions as compared to both controls and FE without schizophrenia. Nevertheless, these parameters could not predict final diagnosis in a discriminant analysis model. Our findings indicate that subtle structural defects are already found by the time of the first psychotic break in schizophrenia, although clinical implications for these differences seem unclear.

Adult↗
PubMed2005

Assessment of myocardial perfusion and viability from routine contrast-enhanced 16-detector-row computed tomography of the heart: preliminary results.

To assess the diagnostic accuracy of 16-detector-row computed tomography (16DCT) of the heart in the assessment of myocardial perfusion and viability in comparison to stress perfusion magnetic resonance imaging (SP-MRI) and delayed-enhancement magnetic resonance imaging (DE-MRI). A number of 30 patients underwent both 16DCT and MRI of the heart. Contrast-enhanced 16DCT data sets were reviewed for areas of myocardium with reduced attenuation. Both CT and MRI data were examined by independent reviewers for the presence of myocardial perfusion defects or myocardial infarctions (MI). Volumetric analysis of the hypoperfusion areas in CT and the infarct sizes in DE-MRI were performed. According to MRI, myocardial infarctions were detected in 11 of 30 cases, and perfusion defects not corresponding to an MI were detected in six of 30 patients. CTA was able to detect ten of 11 MI correctly (sensitivity 91%, specificity 79%, accuracy 83%), and detected three of six hypoperfusions correctly (sensitivity 50%, specificity 92%, accuracy 79%). Assessing the volume of perfusion defects correlating to history of MI on the CT images, a systematic underestimation of the true infarct size as compared to the results of DE-MRI was found (P<0.01). Routine, contrast-enhanced 16-detector row CT of the heart can detect chronic myocardial infarctions in the majority of cases, but ischemic perfusion defects are not reliably detected under resting conditions.

Adult↗
PubMed2005

N-acetyl-aspartate levels in the dorsolateral prefrontal cortex in the early years of schizophrenia are inversely related to disease duration.

Magnetic resonance spectroscopy studies in schizophrenia have revealed consistently reduced N-acetyl aspartate (NAA) levels in chronic patients, but not in recent-onset patients. Studies on the relationship between this marker and disease duration have commonly been negative, although it is also true that they have been conducted in patients with long-standing disease. We compared NAA levels in the dorsolateral prefrontal cortex in 16 recent-onset patients (duration: 1.8+/-0.6 years), 19 chronic patients (duration: 9.7+/-6.1 years), and 20 healthy controls. We studied the NAA/creatine and choline/creatine ratios in the dorsolateral prefrontal cortex in both hemispheres, controlling for the effect of age. Chronic patients had significantly lower NAA/Cr ratios in the left hemisphere compared to recent-onset patients and healthy controls, with no difference in Cho/Cr ratio. There were no differences between controls and recent-onset patients. There was a significant inverse relationship between left-side NAA/Cr and disease duration, suggesting that prefrontal NAA levels may progressively decrease in schizophrenia. Taken within the context of the existing literature, these results indicate that this process may be limited to the early years following the onset of the disease. Therefore, reduced prefrontal levels of NAA may be limited to chronic schizophrenia patients.

Adult↗
PubMed2005

Association between excessive frontal cerebrospinal fluid and illness duration in males but not in females with schizophrenia.

OBJECTIVE: Excessive cortical cerebrospinal fluid (CSF) has been acknowledged as a possible marker of a gray matter loss. This excess in schizophrenia is found predominantly in the prefrontal and temporal regions. We hypothesized that the poorer global outcome and treatment response in males with schizophrenia are related to a greater cortical volume loss as compared to females. SUBJECTS AND METHODS: In order to test this hypothesis we have used magnetic resonance imaging (MRI) to study the cortical (prefrontal, temporal, and hemispheric) CSF values in a group of 85 patients with schizophrenia, of whom 56 were males and 29, females. We calculated the residual values of CSF in the patients based on the data pertaining to 45 control subjects and linear regression, from which the normal effects of age and intracranial volume were discounted. These residual scores constitute a quantitative measurement of the excess of CSF due to the disease. RESULTS: Males, but not females, presented a trend-level significant excess of left prefrontal CSF. The prefrontal and temporal residual values were significantly associated with illness duration in males, but not in females. DISCUSSION: These results conform to the worse outcome and the higher severity of structural abnormalities generally found in schizophrenia in male subjects. CONCLUSION: Our data support the hypothesis of accelerated prefrontal cortical loss in males, but not in females with schizophrenia.

Adult↗
PubMed2005

Prefrontal atrophy in first episodes of schizophrenia associated with limbic metabolic hyperactivity.

Reduced volume and activity of the prefrontal (PF) cortical gray matter (GM) and hippocampal hypermetabolism are repeated findings in schizophrenia. There is still an information deficit about the significance of reduction of PF GM in schizophrenia, and a simultaneous study of PF anatomy and activity and limbic metabolism can contribute to fill that deficit. In order to do so, we used positron emission tomography (PET) with 18-fluoro-deoxy-glucose (FDG) during an attention task and magnetic resonance imaging (MRI) to study a sample of first episodes of psychosis. We included 21 first episodes (FE) of psychosis and 16 healthy controls. A diagnosis of schizophrenia was confirmed in the follow-up in eleven of these patients and ruled out in the remaining 10 cases. Volumes of PF GM were determined and also activity in the same region and in the hippocampus. Residual GM was estimated in the PF region as a quantitative measurement of the degree of atrophy in each individual, using age and intracranial volume data from a set of 45 healthy controls and linear regression. Patients with schizophrenia had lower PF metabolic activation and greater hippocampal activity than controls. FE patients without schizophrenia were no different in any parameter as compared to controls. Patients with schizophrenia presented an inverse and significant association between GM deficit and hippocampal activity that was not observed in controls or in patients without schizophrenia. The same association was previously described by our group using PET in the resting state in recent-onset and chronic patients with schizophrenia. These findings support a loss in PF inhibitory capacity as a possible link between anatomical and functional alterations in schizophrenia.

Adult↗
PubMed2005

Olanzapine-induced cerebral metabolic changes related to symptom improvement in schizophrenia.

The pattern of brain metabolic changes produced by olanzapine has yet to be described, despite the theoretical and clinical interest of this new antipsychotic. We studied a group of 17 schizophrenic patients who underwent two fluoro-deoxyglucose-positron emission tomography (FDG-PET) studies under two different conditions: a baseline scan during treatment with either conventional antipsychotics (n=15) or risperidone (n=2) and a second scan performed 17-24 weeks after switching to olanzapine. PET scans were obtained while performing a standard cognitive paradigm (Continuous Performance Test) and analysed by means of Statistical Parametric Mapping. No significant metabolic changes were found in the comparison between pre- and post-olanzapine conditions. A brain map of the statistical power of our design showed that changes up to 3% in the frontal and up to 8% in the occipital region were not likely to exist (1-beta=0.8). The degree of improvement in positive symptoms was related to the amount of activity decrease in the right orbital region and to the amount of activity increase in the primary visual area. Improvement in negative symptoms was associated with an activity increase in the dorsal prefrontal cortex, and a higher baseline activity in both temporal poles. These correlation patterns suggest that the functional mechanism of action of olanzapine may share traits from both typical and atypical neuroleptics.

Adult↗
PubMed2005

The importance of end-systole for optimal reconstruction protocol of coronary angiography with 16-slice multidetector computed tomography.

OBJECTIVES: Multidetector-row computed tomography coronary images are usually analyzed in mid-diastole (MD). Because of slow coronary motion also in end-systole (ES), we evaluated the impact on image quality of including ES images and defined an efficient reconstruction protocol. MATERIAL AND METHODS: In 50 coronary multidetector-row computed tomography studies, 9 reconstructions (at 10% increments of the RR interval) were graded for image quality. Multiple combinations of reconstructions were compared. RESULTS: MD (60-70% of the RR interval) offered the best image quality. In 44% patients, the best reconstruction for >or=1 coronary was found in ES (20-30%). Their heart rate was higher (68.2+/-9.9 bpm vs. 59.2+/-8.8 bpm, P=0.0014). Combining ES and MD consistently offered superior image quality and less nonevaluable vessels than even larger numbers of diastolic reconstructions alone. A combination of 2-3 reconstructions was most efficient. Adding more reconstructions did not significantly improve results. CONCLUSIONS: Combining ES and MD reconstructions reduces nonevaluable coronary arteries, particularly with higher heart rates. A protocol including 2-3 reconstructions is the most efficient.

Adolescent↗
PubMed2004

Cerebral metabolic changes induced by clozapine in schizophrenia and related to clinical improvement.

RATIONALE: The study of the different effects on brain metabolism between typical and atypical antipsychotics would aid in understanding their mechanisms of action. Clozapine is of special interest, since it is one of the most effective antipsychotic drugs and demonstrates a distinctive mechanism of action in pre-clinical studies with respect to typical neuroleptics. OBJECTIVE: To study the differences in cerebral activity induced by clozapine as compared to those produced by haloperidol. METHODS: [18F]Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) scans were obtained in the resting condition before and after 6 months of treatment with clozapine in 22 treatment-resistant patients with schizophrenia. Before inclusion, patients had been chronically treated with classical drugs, and all of them received haloperidol during the last month. Data were analyzed with statistical parametric mapping (SPM'99) methods, comparing pre-treatment and post-treatment conditions. The association between the changes in symptom scores and metabolism was also assessed to corroborate the functional relevance of possible metabolic changes. RESULTS: Clozapine decreased prefrontal and basal ganglia activity, and increased occipital metabolism, including primary and association visual areas. The change in negative symptoms was related with the decrease of basal ganglia activity; the improvement in disorganization related to the metabolic decrease in the motor area, and the change in positive symptoms was associated to the increase of activity in the visual area. CONCLUSIONS: These results show that haloperidol and clozapine produce different patterns of metabolic changes in schizophrenia. Compared to the haloperidol baseline, clozapine inhibited the metabolic activity of the prefrontal and motor cortical regions and basal ganglia and induced a higher activation of the visual cortex. The improvement in disorganization, negative and positive syndromes with clozapine may be respectively associated with metabolic changes in the motor area, basal ganglia, and visual cortex.

Adult↗
PubMed2004

In vivo 16-slice, multidetector-row computed tomography for the assessment of experimental atherosclerosis: comparison with magnetic resonance imaging and histopathology.

BACKGROUND: Noninvasive imaging can detect early atherosclerotic disease. Magnetic resonance imaging (MRI), because of its excellent spatial resolution, is already established as a tool for plaque characterization. Sixteen-slice, multidetector-row computed tomography (MDCT) was recently introduced into the field of cardiac imaging, with promising results for noninvasive angiography. We compared the capabilities of MDCT and MRI for the assessment of noncalcified, atherosclerotic plaques. METHODS AND RESULTS: Six atherosclerotic rabbits underwent in vivo imaging by MDCT and 1.5-T MRI. MDCT parameters were 120 kV, 120 mA/s, collimation 12x0.75, and spatial resolution 0.6x0.6 mm. MRI parameters were as follows: for proton density, repetition time/echo time (TR/TE) 2300/5.6; for T2, TR/TE 2300/62; and for T1, TR/TE 800/5.6; slice thickness was 3 mm and spatial resolution, 0.3x0.3 mm. Blinded analysis of 3-mm axial reconstructions from MDCT and the carefully matched MRI images (182 sections) showed excellent agreement between both modalities. MDCT yielded a slightly larger lumen area, anteroposterior diameters, and lateral diameters, with no significant differences in total vessel area. The sensitivity and specificity, respectively, to detect noncalcified, atherosclerotic plaques were 89% and 77% for MDCT and 97% and 94% for MRI. Fibrous-rich and lipid-rich plaque could not be differentiated visually, although they showed different attenuation properties (116+/-27 vs 51+/-25 Hounsfield units, P<0.01). CONCLUSIONS: Both techniques allow reliable detection of noncalcified, atherosclerotic plaques and accurate assessment of vessel areas and diameters. MDCT offers the additive value of a very short image acquisition time when compared with MRI. The subtle measurement differences found between modalities may be due to the better spatial resolution of MRI, which probably explains its superiority for tissue characterization.

Animals↗
PubMed2004

Lower prefrontal gray matter volume in schizophrenia in chronic but not in first episode schizophrenia patients.

Although a lower volume of prefrontal (PF) gray matter (GM) in patients with schizophrenia than in normal control subjects is a replicated finding, it is not yet clear whether this finding is present at the onset of illness. Clinical and imaging data suggest that the reduction in PF GM becomes apparent only some years following the onset of illness. To test this hypothesis, we used magnetic resonance imaging to study PF GM and sulcal cerebrospinal fluid (CSF) volumes in 81 schizophrenic patients. A Talairach-based tool was used for segmentation. Subjects included 44 healthy controls, 22 first-episode (FE), treatment-naïve patients with duration of illness of less than 1 year; 29 short-term chronic (SC) patients with durations of illness between 1.5 and 6 years; and 30 long-term chronic (LC) patients with duration of illness of more than 6 years. The data from healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values given individual age and intracranial volume. The FE group did not show significant differences in GM or in CSF volumes compared with controls. However, both the SC and the LC patients showed the expected pattern of lower values for PF GM and an excess of PF sulcal CSF compared with controls. There were no significant differences between SC and LC patients in any of these measurements. There was a significant and inverse association between duration of illness and GM residuals. That association fit a nonlinear rather than a linear model, which was consistent with a decrease of GM volume during the first years following illness onset. No significant differences were found between those receiving atypical and typical antipsychotic drugs during the previous year.

Adult↗
PubMed2004

The role of common single-nucleotide polymorphisms on exon 9 and exon 12 skipping in nonmutated CFTR alleles.

Classic cystic fibrosis (CF) is caused by two loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, whereas patients with nonclassic CF have at least one copy of a mutant gene that retains partial function of the CFTR protein. In addition, there are several other phenotypes associated with CFTR gene mutations, such as idiopathic chronic pancreatitis. In CFTR-associated disorders and in nonclassic CF, often only one CFTR mutation or no CFTR mutations can be detected. In this study, we screened 23 patients with CFTR-associated disorders for CFTR mutations by complete gene testing and quantitative transcript analysis. Mutations were found in 10 patients. In cells from respiratory epithelium, we detected aberrant splicing of CFTR mRNA in all investigated individuals. We observed a highly significant association between the presence of coding single-nucleotide polymorphisms (coding SNPs, or cSNPs) and increased skipping of exon 9 and 12. This association was found both in patients and in normal individuals carrying the same cSNPs. The cSNPs c.1540A>G, c.2694T>G, and c.4521G>A may have affected pre-mRNA splicing by changing regulatory sequence motifs of exonic splice enhancers, leading to lower amounts of normal transcripts. The analysis of CFTR exons indicated that less frequent and weak exonic splicing enhancer (ESE) motifs make exon 12 vulnerable to skipping. The number of splice variants in individuals with cSNPs was similar to previously reported values for the T5 allele, suggesting that cSNPs may enhance susceptibility to CFTR related diseases. In addition, cSNPs may be responsible for variation in the phenotypic expression of CFTR mutations. Quantitative approaches rather than conventional genomic analysis are required to interpret the role of cSNPs.

Adolescent↗
PubMed2004

Assessment of myocardial ischemia and viability using cardiac magnetic resonance.

Cardiac magnetic resonance (CMR) is a burgeoning area of noninvasive cardiac imaging. Today, its clinical utility spans from the qualitative and quantitative assessment of cardiac function and morphology to the challenging task of determining the severity and reversibility of coronary heart disease. Advances in magnet and coil design, pulse sequence, and contrast media have contributed greatly, helping CMR become the multipurpose tool of today's cardiac imaging. This article reviews and explores some of the most exciting clinical applications of CMR in the assessment of coronary artery disease.

Coronary Disease↗
PubMed2004

Analysis of genomic CFTR DNA.

There are numerous methodologies available for the analysis of genomic CFTR DNA. We present here the basic tools to allow a thorough investigation of the CFTR gene, beginning with the identification of potential regulatory regions using DNase I hypersensitive sites, and continuing with methods for the detection of mutations: denaturing High Performance Liquid Chromatography (dHPLC), Single Strand Conformation Polymorphism (SSCP), and allele-specific oligonucleotide (ASO) hybridisation. Also provided is a comprehensive set of PCR primers for the amplification of most regions of the CFTR gene. Full details of the methodologies given are to be found at the European Working Group on CFTR Expression website http://central.igc.gulbenkian.pt/cftr/vr/transcripts.html.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed2004

Methods for RNA extraction, cDNA preparation and analysis of CFTR transcripts.

The scope of this article is to outline some of the basic methods for good quality RNA preparation from mammalian tissues and cells (including epithelial cells). Additionally, we give an outline of common techniques of measuring CFTR gene expression such as quantitative and semi-quantitative reverse transcription (RT) PCR and ribonuclease protection assay (RPA). These methods are designed to detect low abundance transcripts, which apply to CFTR mRNA in most cell types and tissues.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed2004

Quantitative methods for the analysis of CFTR transcripts/splicing variants.

In cystic fibrosis (CF), transcript analysis and quantification are important for diagnosis, prognosis and also as surrogate markers for some therapies including gene therapy. Classical RNA-based methods require significant expression levels in target samples for appropriate analysis, thus PCR-based methods are evolving towards reliable quantification. Various protocols for the quantitative analysis of CFTR transcripts (including those resulting from splicing variants) are described and discussed here.

Cystic Fibrosis↗