Biomedical subjects

Javier Sanz

Publications and source records attributed to Javier Sanz.

52 records · Page 3Linked to original sources

PubMed2004

Direct association between orbitofrontal atrophy and the response of psychotic symptoms to olanzapine in schizophrenia.

The study of cerebral variables associated with response to neuroleptics holds interest from both theoretical and clinical points of view. To date, no studies have aimed to identify predictors of response to olanzapine based on cerebral measurements. Here, we used magnetic resonance to assess the relationship between volumes of the prefrontal (dorsolateral and orbitofrontal) and temporal (temporal lobe and hippocampus) cortical regions and ventricles and, on the other hand, the response to olanzapine in 16 schizophrenic patients. Data from 42 healthy controls were used to calculate volume residuals in the patients, defined as deviations from the expected values, given individual age and intracranial volume. Residuals thus represent the effect of illness on regional measurements. The association between clinical change and those residuals was calculated separately for the positive, negative and total scores from the Positive and Negative Syndrome Scale (PANSS). There was a significant direct association between the degree of orbitofrontal atrophy and the improvement of positive symptoms with olanzapine. No predictors were found for change in the negative dimension. A trend was found for patients with larger ventricles to show a greater global decrease in total PANSS scores. Neither age nor duration of illness explained a significant proportion of the symptom improvement. This result, together with others from the literature, supports the idea that atypical antipsychotics may offer some benefit to patients with significant regional atrophy, and this may have implications for the choice of antipsychotic in clinical practice.

Adult↗

PubMed2004

Evaluation of ischemic heart disease with cardiac magnetic resonance and computed tomography.

Ischemic heart disease is the most common cardiac problem encountered by physicians in their daily practice. In the last few years, computed tomography and magnetic resonance have emerged as robust imaging modalities with great potential for the comprehensive evaluation of patients with this disorder. This article reviews current evidence of the applications where these techniques have demonstrated their usefulness and provides guidance for their use in the clinical management of coronary artery disease.

Coronary Angiography↗

PubMed2004

Biweekly docetaxel and vinorelbine as first-line chemotherapy in metastatic breast cancer.

This study was designed to evaluate the antitumor activity and tolerance of biweekly docetaxel plus vinorelbine as first-line chemotherapy in patients with metastatic breast cancer (MBC). Forty-one patients with measurable disease and no prior chemotherapy for MBC were treated with docetaxel 60 mg/m(2) plus vinorelbine 30 mg/m(2) on day 1, every 2 weeks for a maximum of 12 courses. Median age was 58 years (range, 23-75). Fourteen patients (34.1%) were premenopausal and 27 (65.9%) were postmenopausal. Most patients had received prior neoadjuvant/adjuvant chemotherapy (n = 27, 65.9%), radiation therapy (n = 22, 53.6%), and hormone therapy (n = 21, 51.2%). The most frequent sites of metastasis were bone (n = 18, 43.9%), pleuropulmonary (n = 16, 39%), and liver (n = 14, 34.1%). Twenty-seven patients (65.9%) had more than one site of metastasis. Three hundred and thirty-nine courses were given (median, 8 courses per patient; range, 1-12). Median relative dose intensity was 85% for both docetaxel and vinorelbine. Grade 3/4 toxicities included neutropenia (14 patients, 34.1%), febrile neutropenia (n = 14, 34.1%), and stomatitis (n = 4, 9.8%). No treatment-related deaths were reported. All patients were assessed for response in an intent-to-treat analysis. Four patients (9.8%) had a complete response and 19 (46.3%) had a partial response (overall response rate, 56.1%; 95% CI, 42%-70%). Six patients (14.6%) had stable disease and 12 patients (29.3%) had progressive disease. With a median follow-up of 15.1 months or until death, median duration of response is 12.6 months. Median time to progression is 12.4 months. Median survival time is 19.6 months. This biweekly combination of docetaxel plus vinorelbine is feasible and active as first-line chemotherapy in patients with MBC. This regimen is safe and well tolerated.

Adult↗

PubMed2004

Update in atherothrombotic disease.

Crucial advances in our understanding of the pathogenesis of atherothrombosis, defined as atherosclerosis and its thrombotic complications, have been achieved during the past two decades. The historical hypothesis of pathogenesis ("lipid accumulation") has evolved to integrate several factors contributing to the initiation and evolution of this complex disease. Endothelial dysfunction is considered to be the earliest event in atherogenesis. Inflammation and apoptosis play critical roles in its progression and onset. Tissue factor is postulated to be a central actor in determining plaque thrombogenicity. A hyperreactive state of the blood ("vulnerable blood") may be responsible for one-third of all the acute coronary syndromes. This review will discuss emerging concepts in the pathogenesis of and therapeutic approaches to atherothrombotic disease.

Acute Disease↗

PubMed2003

Anatomical and functional cerebral variables associated with basal symptoms but not risperidone response in minimally treated schizophrenia.

In schizophrenia, structural and functional cerebral variables show an unclear association with clinical features and their value as predictors of response to a typical antipsychotic agents has yet to be determined. The goal of this study was to investigate the relationships between clinical variables (baseline syndromes and response to risperidone) and anatomo-functional brain variables. We studied 19 minimally treated patients with schizophrenia of recent onset using magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) under resting conditions. The following brain variables were studied: volume of the cerebrospinal fluid (CSF) and gray matter (GM) of the dorsolateral prefrontal cortex (DLPFC) and temporal lobe; hippocampal metabolic activity and volume; and metabolic activity of the DLPFC, temporal lobe, putamen and caudate. Anatomical volume measurements were corrected for age and intracranial size using regression parameters determined from a matched sample of control subjects. Using stepwise multiple regression, we assessed the relation between these brain measures and basal scores of symptom dimensions (positive, disorganization, negative and total), as well as their change in response to risperidone. We found that positive and disorganization symptoms improved with risperidone treatment and that hippocampal metabolism, DLPFC CSF volume, and temporal CSF volume predicted baseline symptoms. However, none of the brain measures predicted response to treatment. We conclude that there is evidence of a significant association between basal symptoms and DLPFC atrophy and limbic hyperactivity at rest in recent-onset schizophrenic patients.

Adult↗

PubMed2003

Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia.

Clozapine alleviates the symptoms of a significant proportion of treatment-resistant schizophrenic patients. Previous studies suggest that the response to clozapine may be associated with prefrontal and temporal anatomy as well as with prefrontal, basal ganglia and thalamic metabolism. A sample of 25 treatment-resistant (TR) schizophrenic patients underwent magnetic resonance imaging (MRI) and 18F-deoxyglucose positron emission tomography (PET) before and after treatment with clozapine. We investigated the association between changes in positive, disorganized, and negative schizophrenic syndromes with clozapine treatment and a set of cerebral variables that included total intracranial volume (ICV); hippocampal, dorsolateral prefrontal (DLPF) and temporal gray-matter volume and metabolism; and metabolic activity of the thalamus, pallidum/putamen, and caudate head. Improvement in positive symptoms with clozapine was directly related to temporal gray-matter volume, whereas improvement of disorganization symptoms was inversely related to ICV and hippocampal volume. Patients with high baseline DLPF cortical volume and metabolic activity were more likely to experience improvement in their negative symptoms. We conclude that clinical improvement with clozapine may be related with the anatomy and metabolic activity of specific brain areas, with the structural integrity of the DLPF and temporal regions showing the maximum predictive capacity.

Adult↗

PubMed2003

Cerebral metabolic patterns in chronic and recent-onset schizophrenia.

This article compares the effects of short- and long-term treatment with haloperidol in schizophrenic patients, with the aim of identifying brain metabolic activity patterns common to acute and chronic patients in spite of their different treatment and illness duration. [18F]fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) studies in the resting condition were performed on 18 healthy controls and two groups of schizophrenic patients: recent onset (RO, n=17) minimally treated with haloperidol, and chronic long-term treated patients (LT, n=34). PET scans were analyzed using statistical parametric mapping (SPM'99) and the P-value threshold to assess differences between groups was validated by bootstrapping techniques. Our results show a distinctive pattern of decreased activation of the visual cortex in RO and LT patients, when compared to healthy controls. Insular hypometabolism and a certain degree of hypofrontality were observed in the LT group when compared to RO patients. The main effect of the long-term administration of haloperidol seems to be an increase of cerebellar, basal ganglia and motor area metabolism.

Acute Disease↗

PubMed2003

Characterization of the signal that directs Bcl-x(L), but not Bcl-2, to the mitochondrial outer membrane.

It is assumed that the survival factors Bcl-2 and Bcl-x(L) are mainly functional on mitochondria and therefore must contain mitochondrial targeting sequences. Here we show, however, that only Bcl-x(L) is specifically targeted to the mitochondrial outer membrane (MOM) whereas Bcl-2 distributes on several intracellular membranes. Mitochondrial targeting of Bcl-x(L) requires the COOH-terminal transmembrane (TM) domain flanked at both ends by at least two basic amino acids. This sequence is a bona fide targeting signal for the MOM as it confers specific mitochondrial localization to soluble EGFP. The signal is present in numerous proteins known to be directed to the MOM. Bcl-2 lacks the signal and therefore localizes to several intracellular membranes. The COOH-terminal region of Bcl-2 can be converted into a targeting signal for the MOM by increasing the basicity surrounding its TM. These data define a new targeting sequence for the MOM and propose that Bcl-2 acts on several intracellular membranes whereas Bcl-x(L) specifically functions on the MOM.

Amino Acid Sequence↗

PubMed2003

Haemodynamic monitoring and liver function evaluation by pulsion cold system Z-201 (PCS) during orthotopic liver transplantation.

Pulsion cold system (PCS, COLD) is a haemodynamic monitoring system that allows measurement of cardiac output (CO), partial blood volumes, lung water, and liver function. The aim of the study was to evaluate this monitoring system during human orthotopic liver transplantation (OLT) for the following: (a) to determine agreement between CO measurements via pulmonary artery thermodilution (CO TDpa), and aortic transpulmonary thermodilution (CO TDa); (b) to compare the preload dates obtained with the COLD with central venous pressure (CVP) and pulmonary capillary wedge (PCWP); and (c) to assess the use of the plasma disappearance rate (PDR) of indocyanine green (ICG) as a measure of graft function. Fifteen consecutive patients undergoing OLT were studied. Each patient received a pulmonary artery catheter and a 5F aortic catheter with an integrated thermistor. The thermistor of the aortic catheter were connected to one computer system (COLD-Z201, Pulsion Medical Systems, Munich, Germany). Haemodynamic data were registered an all the phases of OLT. PDR was measured during surgery in 12 patients. Correlations between PDR and the other markers of graft function (transaminases, protrombine time, and bile production) were sought. The correlation coefficient between CO TDa (COLD) and CO TDpa was r = 0.766 (p < 0.001), and an additional analysis according to Bland-Altman was also performed. There was a better correlation between the cardiac index (determined by two monitoring systems) and the volume measurements than the correlation observed with pressure preload parameters. The best correlations were found between the cardiac index in the femoral artery and intrathoracic blood volume index (ITBVI) and pulmonary blood volume index (PBVI) (r = 0.79 and r = 0.72, respectively; p < 0.01). PDR measured in the group patients with bad early graft function were lower (13.6 +/- 2.7) than those in the group with a good graft function (21.6 +/- 9) (p < 0.05). The degree of discrepancy between femoral and pulmonary thermodilution cardiac output measures is very wide during OLT so as to make the techniques using the COLD machine clinically useless. On the other hand, the volumes measured by COLD, specially ITBVI and PBVI, are more useful to asses the pre-load than pressure measurements. In OLT, the PDR measured within the first few hours after liver reperfusion may become a useful tool for early diagnosis of primary graft dysfunction (PDF).

Blood Volume↗

PubMed2003

Presence of methylated arginine derivatives in orthotopic human liver transplantation: relevance for liver function.

Orthotopic liver transplantation (OLT) is a frequent option in the treatment of liver diseases. During the cold ischemia period of the donor liver, there is an accumulation of metabolites that are potent inhibitors of the cytokine-inducible and endothelial nitric oxide synthase isoenzymes. We identified the presence of L-N-monomethylarginine and asymmetric dimethylarginine (ADMA) as the main inhibitors by means of analytic high-pressure liquid chromatography and mass spectrometry techniques. An average ADMA concentration of 450 micromol/L was measured in the preservation medium of donor livers with poor outcomes after OLT. A statistically significant relationship was observed between the concentration of methylated arginine derivatives in the graft and liver function after OLT. These data suggest that measurement of methylated arginine, released after liver protein catabolism, might provide an indication of functional status of the liver that can help the development of strategies intended to improve graft viability.

Animals↗

PubMed2003

Differences between endocarditis with true negative blood cultures and those with previous antibiotic treatment.

BACKGROUND AND AIM OF THE STUDY: High morbidity and mortality are attributed to patients with culture-negative endocarditis. The main reason for negative blood culture in infectious endocarditis (IE) is administration of antibiotics before sample withdrawal. The study aim was to determine any difference in prognosis between patients with 'aborted' culture-negative endocarditis (A-CNE) and those with true culture-negative endocarditis (T-CNE). METHODS: A total of 107 patients with a diagnosis of IE was studied retrospectively. Diagnosis was confirmed pathologically during surgery, at post-mortem examination, or by fulfillment of Duke's criteria. Twenty patients (18.7%) had negative-culture endocarditis and comprised the study population. Of these patients, 14 (70%) had received previous antibiotic therapy (A-CNE), and six (30%) were considered T-CNE cases. In-hospital outcome and clinical characteristics were compared between both patient groups. The main end-point was death or need for surgical repair of the heart valves during hospitalization. RESULTS: There were no significant inter-group differences with respect to mean age, gender distribution, and other clinical characteristics. The composite endpoint of death or surgical repair occurred more frequently in T-CNE patients (100% versus 64%, p = 0.0394). Anatomic complications also occurred more frequently in T-CNE patients, but the difference was statistically not significant. CONCLUSION: Among patients with IE and a negative blood culture, those without previous antibiotic therapy (T-CNE) have the worse prognosis.

Antibiotic Prophylaxis↗

PubMed2002

Association between relative temporal and prefrontal sulcal cerebrospinal fluid and illness duration in schizophrenia.

Changes in sulcal cerebrospinal fluid (CSF) volume have been related to the neurodegeneration hypothesis in schizophrenia. Fifty-three (24 neuroleptic-naive) schizophrenics and a control group (n=26) were studied with MRI to assess regional sulcal CSF values relative to the total volume of brain lobes (prefrontal, orbital, temporal, parietal, and occipital). Segmentation of brain structures was performed using an automatic Talairach-based method. Relative CSF volumes were adjusted for age by means of linear regression from normal subjects; the corrected values were used to assess their relationship with illness duration and age of onset (AOS). The volume of sulcal CSF on prefrontal and temporal lobes (bilateral) was significantly greater in schizophrenic patients and showed a significant positive correlation with illness duration not found in the other regions studied. No significant association between CSF volumes and AOS was found in any region. Our findings support the existence of a degenerative process in schizophrenia located in prefrontal and temporal areas.

Adult↗

PubMed2002

Better prognosis of elderly patients with infectious endocarditis in the era of routine echocardiography and nonrestrictive indications for valve surgery.

OBJECTIVE: It has been reported that endocarditis in the elderly may have a poor outcome. Our aim was to assess the different features and prognosis, if any, in the present time. METHODS: Of 103 patients with proven endocarditis, 31 were 65 years or older and 72 were younger than 65 years. Degenerative heart disease was seen more frequently in the elderly (22.5% vs 2.7%, P =.003). Drug abuse and immunodeficiency virus infection were more common in the younger group, as was tricuspid endocarditis (26.3% vs 0%, P <.001). At clinical presentation cardiac failure (41.9 vs 19.4%, P =.02) and leukocytosis (61.2% vs 40.2%, P =.049) were seen more frequently in the elderly. RESULTS: Despite other similar clinical features, it took longer to diagnose older patients (7.2 +/- 6.2 vs 3.2 +/- 3.5 days, P <.001). Enterococcus infected the aged more often (32.2% vs 13.1%, P =.001). During hospitalization, heart failure and embolization tended to be more common in the elderly and the younger group, respectively. There were no significant differences in the incidence of anatomic complications, the need for operation, and overall mortality. CONCLUSION: Although a worse prognosis has been reported in elderly patients with infective endocarditis, the early use of transesophageal echocardiographic examinations and equal therapeutic options provides a similar outcome when compared with younger subjects.

Aged↗

PubMedDate not supplied

Multimodal neuroimaging studies and neurodevelopment and neurodegeneration hypotheses of schizophrenia.

The interpretation of the huge number of results in schizophrenia research using neuroimaging is uncertain. However, the simultaneous use of complimentary data obtained with these techniques may yield more relevant information in this regard. In this paper we present a series of studies performed by our group in two schizophrenic samples with the use of structural (magnetic resonance imaging, MRI), functional [glucose positron emission tomography (PET) and N-acetyl-aspartate (NAA) magnetic resonance spectrocopy] and neurophysiological techniques (the P300 event-related potential). Transversal and longitudinal measurements were performed.The integrated vision of the results so obtained allows us to propose the hypothesis of a neurodevelopmentally determined state of prefrontal disinihibition, in which the degree of atrophy would directly relate to the metabolic rate. This state would already be present in the first stages of illness and could have neurotoxic consequences in the long term. This would explain the findings of an association between sulcal cerebrospinal fluid (CSF) and illness duration and decreased NAA levels in chronic but not in recent-onset cases. The prefrotnal disinhibition would overstimulate the limbic system and the hippocampus would become overactivated, the metabolic rate at this level being inversely related to P300 amplitude. Clozapine showed a more selective and intense action on that hyperactive metabolic tone than haloperidol.

Journal Article↗

PubMedDate not supplied

[Efficiency of influenza vaccination in the working population in Spain].

INTRODUCTION: Influenza is a major cause of morbidity and mortality worldwide. Currently, licensed influenza vaccines are safe and effective. Any intervention aimed at reducing the burden of illness is worth analyzing from a clinical and economic perspective. OBJECTIVE: To assess the costs and benefits of an influenza vaccination program in the Spanish working population. METHODS: A theoretical model of costs and benefits in terms of productivity savings was developed to compare 2 strategies (vaccination and non-vaccination) in 2 cohorts of 1,000 workers each. The time horizon was 1 year and the study's perspective was societal. MAIN OUTCOME MEASURES: epidemiological and clinical data on the incidence of influenza and the effectiveness of the vaccine. Data on the use of direct and indirect resources were obtained from an expert panel of 5 experts in preventive medicine, microbiology, occupational health, and health economics. Unit costs (euros 2003) were extracted from local databases. A sensitivity analysis was performed with the data on incidence, effectiveness, and work absenteeism due to influenza. RESULTS: In the base case scenario, influenza vaccine saved 35 Euros per worker, of which 88% were savings in work loss days avoided. Threshold values in the sensitivity analysis were 6% for the incidence of influenza and 1.5 days for absence from work, above which the vaccine leads to net savings. CONCLUSIONS: Influenza vaccination in the Spanish working population might result in net resource savings to society at large.

Adolescent↗

PubMedDate not supplied

Direct stenting in single coronary artery arising from the left sinus of Valsalva--a case report.

A patient with postinfarction angina was referred for coronary angiography. In addition to severe atherosclerotic coronary disease, which was responsible for clinical presentation, a single coronary artery arising from the left sinus of Valsalva was found. The authors report the use of direct coronary stent deployment without predilation to treat disease in this rare anomaly.

Aged↗