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Biomedical subjects

Pedro Gil

Publications and source records attributed to Pedro Gil.

17 recordsLinked to original sources

A TAP2 genotype associated with Alzheimer's disease in APOE4 carriers.

Sporadic Alzheimer's disease (AD) appears to be the consequence of the interaction between combinations of genes and environmental factors. Binding with the transporter associated with antigen processing (TAP) is thought to be the main way in which herpes simplex virus type 1 (HSV-1) evades immune surveillance. Several TAP gene polymorphisms were examined and a TAP2 SNP (rs241448) associated with AD found in two independent case-control samples, especially in carriers of the APOE4 allele. These findings are consistent with the hypothesis that human genetic variants facilitating the access of HSV-1 to the brain might result in susceptibility to AD.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Magnetoencephalographic parietal delta dipole density in mild cognitive impairment: preliminary results of a method to estimate the risk of developing Alzheimer disease.

BACKGROUND: Subjects with mild cognitive impairment (MCI) are at a higher risk of experiencing Alzheimer disease (AD). Magnetoencephalographic temporoparietal dipole densities of low-frequency activity are good predictors of individuals' cognitive status, and might be a useful tool to investigate the conversion from MCI to AD. OBJECTIVE: To investigate the role of low-frequency dipole densities as predictors of the risk of developing AD. DESIGN: Whole-head magnetoencephalographic recordings were obtained from 19 probable AD patients, 17 MCI patients, and 17 healthy control subjects. The generators of focal magnetic slow waves were located using a single moving dipole model. RESULTS: Left parietal delta dipole density permitted a reliable classification of AD and MCI patients. The MCI patients were divided into 2 groups based on the median left parietal delta dipole density, and were followed up for 2 years. The estimated relative risk of conversion to AD was increased by 350% in those MCI patients with high left parietal delta dipole density scores. CONCLUSIONS: Results confirmed the important role of parietal delta dipole density in the evaluation of AD and MCI. A magnetoencephalographic-based assessment of AD and MCI patients might be considered a useful clinical test in the near future.

Aged↗

Increased mortality and morbidity associated with thyroidectomy for intrathoracic goiters reaching the carina tracheae.

HYPOTHESIS: Complications associated with thyroidectomy for intrathoracic goiters have been underestimated because of the lack of a precise definition of high-risk patients. DESIGN: Retrospective multicenter multinational review of medical records and radiographic images of patients who underwent thyroidectomy for intrathoracic goiters reaching the carina tracheae. Demographic, clinical, operative, anatomical, and pathological data were recorded. RESULTS: There were 35 patients (mean +/- SE age, 63 +/- 11 years) included in the study. In 4 patients, the goiter was asymptomatic; 10 patients had dysphagia, 24 patients had dyspnea, and 3 patients had superior vena cava syndrome. A median sternotomy was required in 12 patients and a right-sided thoracotomy in 1 patient. The mean +/- SE operative time was 145 +/- 72 minutes (range, 50-360 minutes). Transient hypoparathyroidism developed in 13 patients. Four patients experienced transient hoarseness, and 1 patient had permanent vocal cord paralysis. There were no significant differences between the proportion of patients who underwent or did not undergo sternotomy or thoracotomy regarding vocal cord dysfunction (2 [15%] of 13 patients vs 3 [13%] of 22 patients) or hypoparathyroidism (5 [38%] of 13 vs 6 [28%] of 22 patients). The mean postoperative hospital stay was 10 days (range, 2-84 days). Four patients required reoperation. Two patients died. Nine of 14 patients with thyroid glands weighing at least 260 g required sternotomy vs 3 of 14 patients with thyroid glands weighing less than 260 g (P = .02). Overall, 18 [52%] of 35 patients were discharged without any complication. CONCLUSION: Intrathoracic goiters reaching the carina tracheae carry a high unreported risk of sternotomy, postoperative complications, reoperation, and death.

Adult↗

Atypical small acinar proliferation: review of a series of 64 patients.

OBJECTIVE: To study the evolution of 64 patients initially diagnosed with ASAP (atypical small acinar proliferation). MATERIAL AND METHODS: Between 1998 and the end of 2003, 64 patients were diagnosed at our centre with ASAP. RESULTS: The mean age of the patients assessed was 69 years (SD 6.4 years), the median prostate-specific antigen (PSA) level was 7.1 ng/ml (range 2-39 ng/ml) and 25% of the patients had a suspicious rectal examination. These 64 patients were subjected to re-biopsy. At re-biopsy, we diagnosed 27 patients (42%) with prostate adenocarcinoma. We classified patients into two groups depending on whether they did (n=27) or did not (n=37) have tumours. There were no significant differences in median PSA level between the two groups. The rectal examination was suspicious in 14% of patients without tumours and in 39% with tumours. Radical prostatectomy was applied to 20/28 patients (71%) diagnosed with prostate cancer. In these 20 patients, the median tumour volume was 0.4 cm3 (range 0.1-3.2 cm3) and 44% of the tumours were significant. The 37 patients with an unsuspicious histology were subjected to follow-up for a median of 12 months (range 1-30 months). The median PSA level in these patients was 5.7 ng/ml (range 0.8-28 ng/ml). A third biopsy was performed in three of these patients in view of an elevated PSA level, and one result was positive. CONCLUSIONS: In our experience, a pathological result of ASAP is associated with a definitive diagnosis of prostate cancer in 42% of cases. Moreover, a significant cancer was found in 44% of patients subjected to radical prostatectomy. We therefore systematically perform repeat biopsies on all patients with a histological result of ASAP.

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Target preparation for DNA microarray hybridization.

DNA microarrays are widely used to analyze genome-wide gene expression patterns and to study genotypic variations. They are miniaturized collections of thousands of DNA fragments arrayed on a surface. Based on nucleic acid complementary binding, they serve as a tool to interrogate complex populations of nucleic acids for abundance or binding affinity of particular sequences. Before a nucleic acid (target) can be used for hybridization to the probes of a microarray, it needs to be extracted from the tissue and labeled. Frequently, it also needs to be amplified to increase detection sensitivity. During a hybridization process, labeled target molecules with sequences complementary to the probes are captured quantitatively. Subsequently, a reader measures the amount of label on each probe. To generate accurate and informative data, one of the most critical aspects of these experiments is the quality of both the isolated and the labeled nucleic acid samples. This chapter describes detailed procedures for the preparation of labeled RNA samples for DNA microarray analysis.

Arabidopsis↗

[Jaundice and chronic pancreatitis: common bile duct compression by pancreatic pseudocyst].

In chronic pancreatitis, obstructive jaundice solely due to common bile duct compression by a pancreatic pseudocyst is highly unusual. In most of these cases, the jaundice is due to fibrotic stricture of the intrapancreatic portion of the common bile duct. We report two cases of obstructive jaundice in chronic pancreatitis with pseudocyst. Operative findings and follow-up during the postoperative period demonstrated compression by the pseudocyst over the common bile duct as the only etiologic factor of the jaundice. We believe that intraoperative cholangiography should be performed after drainage of a pseudocyst to correctly assess the etiology of obstruction.

Adult↗

[Tracheoesophageal fistula in an intubated patient. Treatment through exclusion and esophageal patch].

Currently, acquired benign tracheoesophageal fistulas are mainly iatrogenic lesions produced by prolonged tracheal intubation. Their occurrence in intubated patients is infrequent but devastating and their therapeutic resolution is highly complex. We present the case of a patient with an extensive tracheoesophageal fistula following tracheal intubation that was surgically treated through esophageal exclusion (cervical esophagostomy and suture-stapling of the distal esophagus) and closure of the tracheal defect using the posterior esophageal wall.

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[Assessment of the value of monitoring of PTH levels in the standard surgical management of patients with primary hyperparathyroidism].

BACKGROUND AND OBJECTIVE: We decided to evaluate the predictive value of the intra-operative monitoring of PTH concentrations for the standard surgical management of primary hyperparathyroidism (PHP). PATIENTS AND METHOD: 23 patients with PHP were included. RESULTS: When serum PTH values either at anaesthesia induction or at visualization-manipulation of the gland were compared with those values at ten minutes post-excision, we observed 20 cases which were true positive, 1 true negative and 2 false negative. By contrast, when the highest PTH pre-excision value was compared with the PTH value at ten minutes post-excision, false negatives results were eliminated. CONCLUSION: Monitoring of PTH levels during conventional treatment of primary hyperparathyroidism has a good predictive value.

Adult↗

Polymorphism in genes involved in adrenergic signaling associated with Alzheimer's.

To investigate the potential involvement of adrenergic signaling in Alzheimer's disease (AD) pathogenesis, we performed genetic and functional studies of genes initiating the cascade. We chose two functional single-nucleotide polymorphisms (SNPs) in the beta1-adrenergic receptor (ADRB1) and the G protein beta3 subunit (GNB3) genes, respectively, and analyzed their allelic frequencies in a case-control sample of AD. We found that the GNB3 T allele produces a significant risk for AD in individuals homozygous for the ADRB1 C allele, suggesting that the combined effect of both polymorphisms influences AD susceptibility. Interestingly, the co-expression of GNB3 T and ADRB1 C alleles, compared with GNB3 C and ADRB1 G, produced increased cAMP levels and MAPK activation following adrenergic stimulation of transfected human cell lines. Furthermore, the co-expression of these alleles also produced increases in APP expression. These data strongly indicate that the combination of GNB3 and ADRB1 polymorphisms produces AD susceptibility by changing the cell responsiveness to adrenergic stimulation, pointing to the modulation of brain adrenergic receptors as a potential target for novel AD therapeutic strategies.

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Relevance of functional neuroimaging in the progression of mild cognitive impairment.

AIM: To assess whether combining neuropsychological tests and cerebral blood flow markers improves progression accuracy from mild cognitive impairment (MCI) to Alzheimer's disease (AD) than each of them on its own. METHODS: Forty-two patients were investigated prospectively, undergoing baseline and 3-year follow-up neuropsychological tests and neuroimaging with Tc-ECD-SPECT. Twenty-one patients had developed AD while 21 retained their initial diagnosis. The relative blood flow and cognitive differences were studied. Validity parameters, multivariant analysis and logistic regression model were calculated. RESULTS: Patients who deteriorated showed lower scoring than stable subjects in some neuropsychological tests (p = 0.03-0.001) and in relative blood flow in selected regions (8-10%). Low cognitive test scoring and low relative blood flow in some regions showed sensibilities and specificities from 70% to 86% for the diagnosis of early Alzheimer's disease. The relative risk of progression to AD was up to 4.7 times higher for these patients (p = 0.0001). The left frontal relative blood flow, the CAMCOG and orientation scoring were the best data to predict the risk of progression to AD. CONCLUSIONS: The combination of functional imaging and neuropsychological tests can diagnose with high sensitivity and specificity if a patient is suffering cognitive impairment in its early stages, and may aid in predicting the risk of developing dementia.

Brain↗

Regional cerebral blood flow assessed with 99mTc-ECD SPET as a marker of progression of mild cognitive impairment to Alzheimer's disease.

Patients diagnosed with mild cognitive impairment (MCI) have a higher risk of developing Alzheimer's disease (AD). However, not all such patients develop this kind of dementia. The purpose of this prospective study was to assess whether regional cerebral blood flow (rCBF) patterns measured with technetium-99m ethyl cysteinate dimer single-photon emission tomography ((99m)Tc-ECD SPET) in patients suffering from MCI are useful in predicting progression to AD. The study group comprised 42 patients who fulfilled MCI criteria according to the International Psychogeriatric Association and the Alzheimer's Disease Cooperative Study. rCBF was calculated in 16 regions of interest (ROIs). All patients were clinically assessed for 1-3 years. Twenty-one developed AD (group I) while the initial diagnosis of MCI was retained in the other 21 (group II). ROC curves were designed, and sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were determined for each ROI. Compared with group II (MCI), group I (AD) showed a significant reduction of relative blood flow (RBF), ranging from 7% to 10%, in the following areas: right and left prefrontal, right and left frontal, right and left parietal, right and left temporal, right and left frontoparietotemporal and left posterior lateral temporal. Left prefrontal, left frontal and left parietal areas showed sensitivities and specificities higher than 75% and areas below the ROC curve close to 80%. This study shows that RBF patterns in the right and left prefrontal, right and left frontal and left parietal areas are sensitive early markers of progression towards AD. Reduction of rCBF in the medial temporal and anterior lateral temporal cortex has no value as a predictor since it also occurs in patients with MCI who remain stable.

Aged↗

Gene expression phenotypes of Arabidopsis associated with sensitivity to low temperatures.

Chilling is a common abiotic stress that leads to economic losses in agriculture. By comparing the transcriptome of Arabidopsis under normal (22 degrees C) and chilling (13 degrees C) conditions, we have surveyed the molecular responses of a chilling-resistant plant to acclimate to a moderate reduction in temperature. The mRNA accumulation of approximately 20% of the approximately 8,000 genes analyzed was affected by chilling. In particular, a highly significant number of genes involved in protein biosynthesis displayed an increase in transcript abundance. We have analyzed the molecular phenotypes of 12 chilling-sensitive mutants exposed to 13 degrees C before any visible phenotype could be detected. The number and pattern of expression of chilling-responsive genes in the mutants were consistent with their final degree of chilling injury. The mRNA accumulation profiles for the chilling-lethal mutants chs1, chs2, and chs3 were highly similar and included extensive chilling-induced and mutant-specific alterations in gene expression. The expression pattern of the mutants upon chilling suggests that the normal function of the mutated loci prevents a damaging widespread effect of chilling on transcriptional regulation. In addition, we have identified 634 chilling-responsive genes with aberrant expression in all of the chilling-lethal mutants. This reference gene list, including genes related to lipid metabolism, chloroplast function, carbohydrate metabolism and free radical detoxification, represents a potential source for genes with a critical role in plant acclimation to suboptimal temperatures. The comparison of transcriptome profiles after transfer of Arabidopsis plants from 22 degrees C to 13 degrees C versus transfer to 4 degrees C suggests that quantitative and temporal differences exist between these molecular responses.

Acclimatization↗

Malignant mesothelioma of the tunica vaginalis. Report of a case without risk factors and review of the literature.

Malignant mesothelioma of the tunica vaginalis testis is an aggressive tumour with local recurrence being distant metastases the main feature of the clinical course. Usually appears over the fourth decade, having a strong relationship with occupational exposure to asbestos and long lasting hydrocele. We introduce a case of a 78-year-old caucasian male who developed a malignant mesothelioma without personal history of hydrocele or exposure to asbestos. A revision of the current literature is performed to summarize the recent therapeutic options as well as new diagnostic tools.

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Focal temporoparietal slow activity in Alzheimer's disease revealed by magnetoencephalography.

BACKGROUND: Patients suffering from Alzheimer's disease exhibit more activity in the conventional electroencephalographic delta and theta bands. This activity concurs with atrophy and reduced metabolic and perfusion rates, particularly in temporoparietal structures. METHODS: Whole-head magnetoencephalographic recordings were obtained from 15 patients diagnosed with Alzheimer's disease and 19 healthy control subjects during a resting condition. The generators of focal magnetic slow waves were located employing a single moving dipole model. RESULTS: Dipole density in the delta and theta bands was enhanced in the Alzheimer's disease group compared with healthy control subjects. Slow-wave activity differed significantly between groups in temporoparietal regions of both hemispheres. Right temporoparietal slow-wave activity covaried with cognitive performance, whereas left temporal delta activity varied with a functional status scale. CONCLUSIONS: Our results support the predominant role of the temporoparietal areas in the diagnosis of Alzheimer's disease. Magnetoencephalography and the source analysis of focal slow activity in particular provide interesting and potentially clinically useful tools to assess functional modifications of patients' brain and to evaluate its relationship with the cognitive status.

Aged↗

Malondialdehyde: a possible marker of ageing.

BACKGROUND: Numerous recent studies have suggested that oxidative damage may be important in the ageing process, and lipid peroxidation is an important biological consequence of oxidative cellular damage. OBJECTIVE: The aim of this work was to analyze the activities of the two protective enzymes, superoxide dismutase (SOD) and catalase (CAT), and the levels of malondialdehyde (MDA) to examine the relationship between the ageing process and defence antioxidant and lipid peroxidation. METHOD: SOD activity was measured in red blood cells using the Minami and Yoshikawa method; CAT activity was measured in hemolysates by the Aebi method, and MDA levels were measured in erythrocytes by high-performance liquid chromatography. RESULTS: SOD activity shows statistically significant differences between newborns and the rest of the sample (ANOVA p < 0.001; Student-Newman-Keuls test p < 0.001). CAT activity did not show significant differences between the age groups. We observed statistically significant differences in MDA levels between the different groups (ANOVA p < 0.001; Student-Newman-Keuls test p < 0.05). In the regression analysis and rectilinear/curvilinear adjustment compared to age, SOD and CAT showed coefficients close to zero (SOD linear = 0.16; SOD exponential = 0.15; CAT linear = 0.056; CAT exponential = 0.068), indicating in that way their independence from age. Only MDA obtained a regression coefficient superior to 0.75 (p < 0.05). The best adjustment was reached through an exponential expression, giving the following parametric relation: MDA = 103.117e(0.0021.AGE). No statistically significant variation in SOD and CAT activity and MDA levels, related to sex could be demonstrated. CONCLUSIONS: Our data show that old age is associated with an increase in systemic oxidative stress.

Adult↗

Neuropsychological markers of progression from mild cognitive impairment to Alzheimer's disease.

To find early clinical markers that may predict a likely progression to Alzheimer's disease (AD), the authors performed neuropsychological tests on 82 mild cognitive impairment (MCI) subjects. After 3 years, 38 patients developed AD while 44 retained the diagnosis of MCI. The cognitive differences between the groups were studied. Patients who developed AD showed significantly lower values than did MCI subjects in some neuropsychological scores (P = .02-.001), with sensitivities and specificities higher than 84% and 64%, respectively, for detecting early-onset AD, with a 7.9-fold increased risk of converting to AD (P < .001). Regarding the logistic regression model, the CAMCOG Memory and Perception cognitive screening items were the optimum independent tools to classify the patients who will progress to AD, showing a relative risk of progression of 10.5 (P = .002), 5.5 (P = .008), and 3.9 times (P = .05), respectively, with a sensibility of of 92.1% and a specificity 72.7%.

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