The homozygosity of the 10-repeat allele at dopamine transporter gene (DAT1) seems to be associated with a poor response to methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD). This pilot study aimed to simultaneously assess polymorphisms at DAT1, response to MPH, and neuroimaging. Only ADHD children with at least a moderate response to MPH were included. Significantly higher regional cerebral blood flows assessed by single photon emission computerized tomography (SPECT) were detected in medial frontal and left basal ganglia areas in children with homozygosity for the 10-repeat allele at DAT1 gene (n = 4) than in children without this genotype (n = 4) (P < 0.05). These findings provide a preliminary connection between pharmacogenetics and neurobiological investigations on stimulant treatment of ADHD.
Neuroimaging studies have suggested the involvement of several brain areas in attention-deficit/hyperactivity disorder (ADHD). Genetic investigations have supported the role of both dopamine D4 receptor gene (DRD4) and dopamine transporter gene (DAT1) in the vulnerability to the disorder. This study evaluates whether the presence of risk alleles at DRD4 and/or DAT1 genes is associated with differences in regional cerebral blood flow (rCBF) in a sample of ADHD boys. The rCBF was compared between ADHD patients with and without risk alleles at DRD4 (7-repeat allele) and/or at DAT1 (homozygosis for the 10-repeat allele) genes by single photon emission computed tomography (SPECT) during continuous performance test. Images were analyzed using statistical parametric mapping (SPM-99). No significant differences in rCBF were found both between ADHD boys with and without the 7-repeat allele at DRD4 locus, as well as between ADHD boys homozygous for the 10-repeat allele and ADHD subjects with other genotypes at the DAT1 locus. However, a significantly higher perfusion in the right middle temporal gyrus was found in the group with risk alleles at both DRD4 and DAT1 loci (n = 6) compared to ADHD boys without risk alleles at both loci (n = 28) (P < 0.05). Our findings suggest that a higher recruitment in middle temporal gyrus, an area associated to working memory and selective attention, should exist to compensate a putative effect of the interaction between these dopaminergic genes.
Methylphenidate (MPH) is the most commonly prescribed treatment for attention-deficit/hyperactivity disorder (ADHD). The therapeutic mechanisms of MPH are not, however, fully understood. We studied the effects of MPH on brain activity in male children and adolescents with ADHD, using the blood flow radiotracer technetium-99m ethyl cysteinate dimer ((99m)Tc-ECD) and single-photon emission tomography (SPET). The study was randomized, double blind, and placebo controlled (MPH group, n=19; placebo group, n=17), Radiotracer was administered during the performance of the Continuous Performance Test and before and after 4 days of MPH treatment. Statistical parametric mapping (SPM99) analysis showed a significant reduction in regional cerebral blood flow in the left parietal region in the MPH group compared with the placebo group (P<0.05, corrected for multiple comparisons). Our findings suggest that the posterior attentional system, which includes the parietal cortex, may have a role in the mediation of the therapeutic effects of MPH in ADHD.
The early demonstration of lung involvement in systemic lupus erythematosus (SLE) patients is a difficult but important task. In the present study we attempted to identify abnormalities in pulmonary clearance of 99m Tc-DTPA in SLE, correlating their clearance data with clinical findings and disease activity. Forty-six consecutive SLE patients with and without active disease (LACC score) and 30 normal volunteers were studied. All subjects were submitted to pulmonary scintigraphy with 99m Tc-DTPA to evaluate the pulmonary clearance, and to a chest X-ray, and SLE patients were submitted to tests of disease activity, spirometry, arterial blood gases and tests to assess acute-phase proteins. Pulmonary clearance was faster in SLE patients with active disease when compared to normal controls [half-life of 67.04 min (51.52-82.55 min) in active SLE versus 85.87 min (78.85-92.87 min) in controls, P<0.05] and there was a higher frequency of abnormal clearance rates in patients with active disease (11 of 26 patients, 42.3%) when compared with SLE patients without disease activity (2 of 20 patients, 10%) (P = 0.04). A significant correlation was observed between the clearance rates and cough (P<0.05), but not between the clearance rates and dyspnea symptoms or radiological findings, duration of SLE disease, antinuclear antibody titers and patterns, C-reactive protein or anti-double stranded DNA antibodies. We conclude that the pulmonary clearance of 99m Tc-DTPA is increased in SLE patients with active disease.
Objective: to assess lung perfusion patterns in inpatients with acute viral bronchiolitis using quantitative 99m Tc-MAA scintigraphy so as to establish an association with clinical and radiological findings.Methods: a comparative, prospective case series study with a focus on diagnosis was carried out in a population of patients with acute viral bronchiolitis admitted to Hospital de Clínicas de Porto Alegre. Inclusion criteria were age between 01 and 24 months and first sudden-onset wheezing episode, suggesting bronchiolitis. The patients in the study were submitted to clinical, radiological and 99m Tc-MAA lung perfusion evaluation during the first 24 hours of admission. Statistical analysis employed t test, taking into consideration a significance level of 0.05.Results: the regional distribution of lung blood flow in the 38 patients studied was more pronounced in the upper section of the left lung in relation to the right lung (P<0.001). The distribution gradients of blood flow between the upper and middle and upper and lower sections were higher in the left lung (P<0.001). The distribution gradients of blood flow between the middle and lower sections were higher in the right lung, but without significance. The distribution gradient of the pulmonary flow in the anteroposterior axis was >1.0 in the upper and middle sections of both lungs. In the lower section it was >1.0 only in the right lung (P<0.007). There was no association between lung blood flow distribution patterns and clinical or radiological findings.Conclusion: there was no evidence of an association between lung blood flow distribution and ventilation-perfusion ratio in hospitalized infants with acute viral bronchiolitis; only a tendency to redirect lung blood flow towards upper lung sections was observed.J Pediatr (Rio J) 2002; 78 (2): 133-9: regional blood flow, pulmonary circulation, perfusion, radionuclide imaging, macroaggregated albumin with technetium Tc 99m, bronchiolitis. ResumoObjetivo: avaliar a distribuição da perfusão pulmonar em pacientes hospitalizados com bronquiolite aguda, por meio de cintilografia pulmonar perfusional quantitativa com 99m Tc-MAA, estabelecendo associação com avaliações clínica e radiológica concomitantes.Pacientes e métodos: foi realizado um estudo de série de casos, prospectivo, comparativo, com enfoque diagnóstico, em amostra por conveniência de pacientes hospitalizados com bronquiolite aguda, baseada em critérios clínicos, idade entre 1 e 12 meses, como primeiro episódio de sibilância expiratória de início súbito, sugestivo de bronquiolite. Foram realizadas avaliações clínica, radiológica e da perfusão pulmonar nas primeiras 24 horas da admissão. Foi utilizado o teste t de Student, com o nível de significância de 0,05, na análise estatística.Resultados: nos 38 pacientes estudados, a distribuição do fluxo sangüíneo pulmonar regional foi maior na região superior do pulmão esquerdo em relação ao direito (p<0,001). Os gradientes de distribuição do fluxo pulmonar entre as regiões superior e média e superior ...
There was no evidence of an association between lung blood flow distribution and ventilation-perfusion ratio in hospitalized infants with acute viral bronchiolitis; only a tendency to redirect lung blood flow towards upper lung sections was observed.
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