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Biomedical subjects

Benito P Damasceno

Publications and source records attributed to Benito P Damasceno.

13 recordsLinked to original sources

Promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene: a novel risk factor for arterial ischemic stroke among young adults and children.

BACKGROUND AND PURPOSE: Plasma glutathione peroxidase (GPx-3)-deficiency increases extracellular oxidant stress, decreases bioavailable nitric oxide, and promotes platelet activation. The aim of this study is to identify polymorphisms in the GPx-3 gene, examine their relationship to arterial ischemic stroke (AIS) in a large series of children and young adults, and determine their functional molecular consequences. METHODS: We studied the GPx-3 gene promoter from 123 young adults with idiopathic AIS and 123 age- and gender-matched controls by single-stranded conformational polymorphism and sequencing analysis. A second, independent population with childhood stroke was used for a replication study. We identified 8 novel, strongly linked polymorphisms in the GPx-3 gene promoter that formed 2 main haplotypes (H1 and H2). The transcriptional activity of the 2 most prevalent haplotypes was studied with luciferase reporter gene constructs. RESULTS: The H2 haplotype was over-represented in both patient populations and associated with an independent increase in the risk of AIS in young adults (odds ratio=2.07, 95% CI=1.03 to 4.47; P=0.034) and children (odds ratio=2.13, 95% CI=1.23 to 4.90; P=0.027). In adults simultaneously exposed to vascular risk factors, the risk of AIS approximately doubled (odds ratio=5.18, 95% CI=1.82 to 15.03; P<0.001). Transcriptional activity of the H2 haplotype was lower than that of the H1 haplotype, especially after upregulation by hypoxia (normalized relative luminescence: 3.54+/-0.32 versus 2.47+/-0.26; P=0.0083). CONCLUSIONS: These findings indicate that a novel GPx-3 promoter haplotype is an independent risk factor for AIS in children and young adults. This haplotype reduces the gene's transcriptional activity, thereby compromising gene expression and plasma antioxidant and antithrombotic activities.

Adult↗

Intrathecal immunoglobulin G synthesis and brain injury by quantitative MRI in multiple sclerosis.

OBJECTIVES: It was the aim of this study to evaluate if the quantitative intrathecal immunoglobulin G (IgG) synthesis correlates with the brain atrophy and the total lesion volume (TLV) in brain magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients. METHODS: A total of 50 patients with relapsing-remitting MS were included in this study. MRIs were performed and cerebrospinal fluid samples were collected during the diagnostic determination when patients were in remission without treatment. RESULTS: At study baseline, IgG index values were elevated in 36 patients (72%), and oligoclonal IgG bands were positive in 42 of 50 patients (84%). Brain MRI was abnormal in 94% of patients, and, compared with healthy controls, brain atrophy was observed in MS patients. A positive correlation among IgG index, cerebrospinal fluid leukocyte count and TLV was observed; the Expanded Disability Status Scale correlated positively with TLV and the number of lesions, although a significant relationship between disability and brain atrophy was not demonstrated. CONCLUSIONS: Although new parameters will be necessary in longitudinal studies to characterize the axonal injury in various stages of the disease, the data suggest that the high intrathecal IgG synthesis may predict a greater brain lesion burden.

Adolescent↗

Theory of mind and the frontal lobes.

BACKGROUND: Theory of mind (ToM) is the ability to attribute mental states to other individuals. Its cerebral organization is not enough established, even though the literature suggests the relevant role of the frontal lobes. OBJECTIVE: To evaluate frontal lobe patients and controls in ToM tests. METHOD: We studied 20 patients with lesions limited to the frontal lobes (as shown by CT or MRI), and 10 normal control subjects by means of ToM tests (recognizing himself in mirrors, false belief, first and second order ToM tasks), as well as tests of other cognitive functions (counter-proofs). RESULTS: Patients and controls performed similarly in ToM tests. There was significant difference between frontal subgroups (left, right, bifrontal) in the double-bluff task (second order ToM) (p=0.021), without relation to verbal fluency (p=0.302) or delayed recall ability (p=0.159). The only two patients with deficits in ToM tasks had impairment of social behavior. CONCLUSION: Frontal lesions do not necessarily implicate in ToM deficits, which may occur when such lesions are associated to disturbance of social behavior.

Adult↗

Memory and language impairments and their relationships to hippocampal and perirhinal cortex damage in patients with medial temporal lobe epilepsy.

Chronic medial temporal lobe epilepsy (MTLE) is associated with memory loss due to damage in the hippocampal system. To investigate the relationship between volume of medial temporal lobe structures and performance on neuropsychological tests, we studied 39 consecutive patients with MTLE and unilateral hippocampal atrophy (HA) determined by volumetric magnetic resonance imaging (MRI). Structures of interest comprised hippocampus, amygdala, and entorhinal, perirhinal, parahippocampal, and temporopolar cortices. The findings indicated that (1) performance was significantly worse in the group with left HA as compared with the group with right HA on general memory, verbal memory, delayed recall, and verbal fluency tests and the Boston Naming Test (BNT), and (2) the volume of the left hippocampus and also the degree of asymmetry of perirhinal cortex volume were significant and independent predictors of performance on general memory, verbal memory, and verbal fluency tests and the BNT in patients with MTLE.

Adolescent↗

Primitive reflexes and cognitive function.

BACKGROUND: Data on the prevalence of primitive reflexes (PR) in adulthood, their pathological significance and relationship to age and cognition are controversial. OBJECTIVE: To study the relationship between PR and cognition in 30 patients with probable Alzheimer's disease (AD) and 154 control subjects. METHOD: Diagnosis of probable AD was based on DSM-IV, NINCDS-ADRDA, and CAMDEX criteria. Primitive reflexes were quantified from zero (absent) to 1 (mild) or 2 (markedly present). The Cognitive Abilities Screening Instrument-Short Form (CASI-S) was used to evaluate registration, temporal orientation, verbal fluency and recall. A drawing test was added. RESULTS: Most frequent PR among demented and controls were suck (77% and 62%, respectively) and snout (60% and 27%), followed by glabellar (30% and 19%), paratonia (37% and 5%), and palmomental (23% and 5%). None of controls had more than three PR. Frequency of PR tended to increase with age and cognitive deterioration. Grasp and Babinski responses were found only in dementia patients. Primitive reflexes were not correlated with each other, except snout with suck, and snout with glabellar reflex. CONCLUSION: The finding of grasp and Babinski sign, or the presence of more than three primitive signs, particularly the combination of paratonia, snout, suck, and palmomental reflexes strongly suggests brain dysfunction, especially when these signs are marked and accompanied by deficits in orientation, recall, verbal fluency, and constructional praxis.

Adult↗

[Validation of the Brazilian version of mini-test CASI-S].

OBJECTIVE: To determine CASI-S accuracy in the diagnosis of dementia. METHOD: The Cognitive Abilities Screening Instrument - Short Form (CASI-S) was applied in 43 Alzheimer's disease (AD) patients and 74 normal controls. AD diagnosis was based on DSM-IV, NINCDS-ADRDA, and CAMDEX. CASI-S includes: registration, temporal orientation, verbal fluency (4-legged animals in 30s), and recall (3 words). Its maximum score is 33 points. A copy of 2 pentagons was added. RESULTS: ROC curve showed an accuracy of 0.87, with standard error of 0.032, and 95% confidence intervall between 0.795 and 0.925. The cut-off score for cognitive deficit was 23, with sensitivity of 76.7%, specificity 86.5%, positive likelihood ratio (LR) 5.68, and negative LR 0.27. The cut-off score for subjects 70 years or older was 20, with sensitivity of 71.4% and specificity 97.1%. CONCLUSION: CASI-S is a practical test, with high specificity, particularly in individuals above 70 years of age. The adding of the drawing test did not improve its accuracy.

Adult↗

Cerebral venous thrombosis: influence of risk factors and imaging findings on prognosis.

PURPOSE: To investigate imaging findings, risk factors and outcome in patients with cerebral venous thrombosis (CVT). METHODS: Records of all patients with diagnosis of CVT between 1992 and 2002 were reviewed. Patients with CNS infection and with CVT secondary to invasive procedures were excluded. Inherited and acquired thrombophilia were searched in all patients. RESULTS: Twenty-four patients (18 women, 6 men) with mean age of 29.5 years (range 3-48 years) were identified. Mean follow-up was 44 months (range 11-145 months). The most common symptoms were headache (75%), vomiting (33%) and impairment of consciousness (21%). Probable causes of CVT could be determined in 21 (88%) patients: pregnancy or puerperium in six (25%), oral contraceptive use in four (17%), head trauma in two (8%), mastoiditis in one (4%), nephrotic syndrome in one (4%), systemic disease in three (13%), and inherited thrombotic risk factors in four (17%) patients. CVT associated with pregnancy, puerperium and use of oral contraceptives had a significant better outcome than CVT caused by inherited thrombophilia or systemic disease (OR=14.4; p=0.02). CT scans were abnormal in 15 (62.5%) patients and MRI with gadolinium was abnormal in all. Those with parenchymal involvement had neurological sequelae during follow-up. All were treated with heparin followed by oral anticoagulants, and none had new or worsening of pre-existing intracerebral hemorrhage. CONCLUSION: MRI is superior to conventional CT for diagnosing CVT. Patients with parenchymal lesions, thrombophilia and antiphospholipid syndrome had greater risk to be left with neurological sequelae. Anticoagulant therapy did not predispose to further intracerebral hemorrhage.

Adolescent↗

Whipple's disease with neurological manifestations: case report.

Whipple's disease (WD) is an uncommon multisystem condition caused by the bacillus Tropheryma whipplei. Central nervous system involvement is a classical feature of the disease observed in 20 to 40% of the patients. We report the case of a 62 year old man with WD that developed neurological manifestations during its course, and discuss the most usual signs and symptoms focusing on recent diagnostic criteria and novel treatment regimens.

Biopsy↗

The combined effect of paraoxonase promoter and coding region polymorphisms on the risk of arterial ischemic stroke among young adults.

BACKGROUND: Serum paraoxonase (PON1) is a high-density lipoprotein-associated esterase with antioxidant and antiatherogenic properties that has recently been implicated in the pathogenesis of cardiovascular disease. Interindividual variability in PON1 levels is determined by the Q192R and L55M coding region polymorphisms and by 2 recently described polymorphisms in the promoter of the PON1 gene, C(-107)T and G(-824)A. OBJECTIVE: To determine the association of the PON1 promoter polymorphisms with arterial ischemic stroke (AIS) in the young. DESIGN. SETTING, AND PATIENTS: We studied 118 young patients (age, <45 years) with a first nonfatal AIS of undetermined etiology and 118 control subjects, matched simultaneously for age and sex. The PON1 C(-107)T polymorphism was determined by single-stranded conformational polymorphism analysis and the G(-824)A substitution by polymerase chain reaction and restriction enzyme digestion. RESULTS: The presence of the low-expressor -107T allele was associated with an independent increase in overall risk of AIS (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.06-6.78; P =.04) by conditional multiple logistic regression analysis. Among individuals with the 192RR genotype, the presence of the -107T allele led to a higher but nonsignificant risk, yielding an OR of 4.15 (95% CI, 0.35-48.76; P =.15) when compared with noncarriers of the T allele and 17.01 (95% CI, 1.74-166.35; P =.02) when compared with noncarriers of either variant. No significant difference between groups was found regarding the G(-824)A polymorphism. CONCLUSION: These findings suggest that the PON1 -107T allele is independently associated with the risk of AIS, in addition to interacting with and potentiating the risk conferred by the Q192R polymorphism.

Adult↗

Evidence of memory impairment in asymptomatic individuals with hippocampal atrophy.

Our objective was to investigate if MRI-determined hippocampal atrophy (HA) is associated with memory deficits independent of seizure frequency. We studied three groups of individuals: (1) 10 asymptomatic first-degree relatives of patients with familial mesial temporal lobe epilepsy (FMTLE), all of them with HA; (2) 14 patients with benign FMTLE, 9 with HA, and 5 with normal hippocampal volumes; and (3) 16 patients with refractory FMTLE, all but one with HA. HA was associated with lower scores on general memory (P=0.015), verbal memory (P=0.020), and delayed recall (P=0.028), even in those with no or few seizures in life. General linear model analyses showed that the interaction between seizure outcome and HA was associated with worse verbal memory (P=0.029), visual memory (P=0.022), and delayed recall (P=0.039) as compared with each of these factors independently. Our findings suggest that seizures and HA are independently associated with memory impairment.

Adolescent↗

Subcutaneous and cerebral cysticercosis.

Cysticercosis is a human infestation, which is considered the most common cause of seizures worldwide. The subcutaneous lesions can help in the diagnosis of neurocysticercosis. We describe a case of a 45-year-old patient with multiple cutaneous nodules first seen 2 years ago that were increasing in number, and normal neurologic and fundoscopic examination. Neurologic symptoms started 3 months before hospital admission as a mild headache and muscular weakness. The imaging examinations showed a massive central nervous system involvement. Physicians must be aware of the importance of subcutaneous nodule examination for the diagnosis of neurocysticercosis.

Animals↗

[Dementia in patients of Hospital das Clínicas da UNICAMP].

OBJECTIVE: To report the relative frequencies of the causes of dementia in patients seen at UNICAMP Hospital. METHOD: From 1989 to 1998, 261 dementia patients were admitted (89.7% studied retrospectively, and 10.3%, prospectively); mean age 63.5 years (+/-13.2), and education 3.6 years +/- 3.9; 25% illiterate). Diagnosis of dementia and its subtypes was based on DSM-IV criteria, CAMDEX, NINCDS-ADRDA, NINDS AIREN/ADDTC, Lund-Manchester, besides tap-test, including laboratory and neuroimaging examinations. RESULTS: Sixty five patients (24.9%) had vascular dementia, 62 ( 23.7%) Alzheimer's, 29 (11.1%) depressive pseudodementia, 28 (10.9%) normal pressure hydrocephalus, 14(5.4%) mixed, 12 (4.6%) post-traumatic, 9 (3.4%) frontotemporal and 38 (14.5%) had diverse or unknown causes. Dementia was minimal or mild in 123 (47.1%), moderate in 95 (36.4%), and severe in 43 (16.5%). CONCLUSION: Frequency of vascular dementia was 24.9%, Alzheimer's 23.7%, and normal pressure hydrocephalus 10.7%, in disagreement with that found in the neurological literature (20-30%, 50%, and 1-4%, respectively), probably because we are dealing with cases admitted to a tertiary university hospital. Epidemiological studies are needed to disclose the true proportion of these dementia syndromes in the population.

Adult↗

Paraoxonase 192 Gln-->Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults.

BACKGROUND AND PURPOSE: The etiology of arterial ischemic stroke (AIS) in the young remains unknown in one third of patients. Serum paraoxonase (PON1) is an HDL-associated esterase that hydrolyzes products of lipid peroxidation and prevents the oxidation of LDL. Two common polymorphisms in the PON1 gene, the 192 Gln (Q) --> Arg (R) and 55 Leu (L) --> Met (M) substitutions, determine interindividual variation in PON1 activity. The association of these polymorphisms with the risk of AIS remains controversial. METHODS: We analyzed 118 patients (64 women) with a first nonfatal AIS occurring <45 years of age and 118 1:1 age (+/-2 years)- and sex-matched controls. The PON1 polymorphisms were determined by polymerase chain reaction amplification and restriction digestion. RESULTS: The prevalence of the PON1 192RR genotype (P=0.006) and the frequency of the R allele (P=0.010) were significantly increased among young AIS patients compared with controls. After adjustment for conventional vascular and prothrombotic risk factors, the 192RR genotype remained independently associated with a 4-fold increase in the risk of AIS (odds ratio=4.1; 95% CI, 1.14 to 14.73). Subanalyses stratified by the presence of vascular risk factors and ethnicity did not significantly modify the effect of the PON1 192 polymorphism on AIS risk. No significant differences were found between patients and controls regarding the PON1 55 polymorphism. CONCLUSIONS: These findings suggest that the PON 192RR genotype is independently associated with an increased risk of nonfatal AIS among young adults. Further studies are necessary to understand better the mechanistic implications of these observations in the development of AIS in the young.

Adult↗