RESUMO
BACKGROUND: The group of susceptibility genes for pheochromocytoma that included the proto-oncogene RET (associated with multiple endocrine neoplasia type 2 [MEN-2]) and the tumor-suppressor gene VHL (associated with von Hippel-Lindau disease) now also encompasses the newly identified genes for succinate dehydrogenase subunit D (SDHD) and succinate dehydrogenase subunit B (SDHB), which predispose carriers to pheochromocytomas and glomus tumors. We used molecular tools to classify a large cohort of patients with pheochromocytoma with respect to the presence or absence of mutations of one of these four genes and to investigate the relevance of genetic analyses to clinical practice. METHODS: Peripheral blood from unrelated, consenting registry patients with pheochromocytoma was tested for mutations of RET, VHL, SDHD, and SDHB. Clinical data at first presentation and follow-up were evaluated. RESULTS: Among 271 patients who presented with nonsyndromic pheochromocytoma and without a family history of the disease, 66 (24 percent) were found to have mutations (mean age, 25 years; 32 men and 34 women). Of these 66, 30 had mutations of VHL, 13 of RET, 11 of SDHD, and 12 of SDHB. Younger age, multifocal tumors, and extraadrenal tumors were significantly associated with the presence of a mutation. However, among the 66 patients who were positive for mutations, only 21 had multifocal pheochromocytoma. Twenty-three (35 percent) presented after the age of 30 years, and 17 (8 percent) after the age of 40. Sixty-one (92 percent) of the patients with mutations were identified solely by molecular testing of VHL, RET, SDHD, and SDHB; these patients had no associated signs and symptoms at presentation. CONCLUSIONS: Almost one fourth of patients with apparently sporadic pheochromocytoma may be carriers of mutations; routine analysis for mutations of RET, VHL, SDHD, and SDHB is indicated to identify pheochromocytoma-associated syndromes that would otherwise be missed.
Assuntos
Proteínas de Drosophila , Mutação em Linhagem Germinativa , Proteínas Ferro-Enxofre/genética , Ligases/genética , Complexos Multienzimáticos/genética , Oxirredutases/genética , Feocromocitoma/genética , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Succinato Desidrogenase/genética , Proteínas Supressoras de Tumor , Ubiquitina-Proteína Ligases , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Complexo II de Transporte de Elétrons , Feminino , Tumor Glômico/genética , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2a/genética , Mutação de Sentido Incorreto , Subunidades Proteicas , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret , Proteína Supressora de Tumor Von Hippel-Lindau , Doença de von Hippel-Lindau/genéticaRESUMO
BACKGROUND: The number of multislice CT (MSCT) scans performed in polytraumatized children has increased rapidly. There is growing concern regarding the radiation dose in MSCT and its long-term consequences, especially in children. OBJECTIVE: To determine the effective dose to polytraumatized children who undergo whole-body MSCT. MATERIALS AND METHODS: A total of 51 traumatized children aged 0-16 years underwent a polytrauma protocol CT scan between November 2004 and August 2006 at our institution. The effective dose was calculated retrospectively by a computer program (CT-Expo 1.5, Hannover, Germany). RESULTS: The mean effective dose was 20.8 mSv (range 8.6-48.9 mSv, SD +/- 7.9 mSv). There was no statistically significant difference in the effective dose between male and female patients. CONCLUSION: Whole-body MSCT is a superior diagnostic tool in polytraumatized children with 20.8 mSv per patient being a justified mean effective dose. In a potentially life-threatening situation whole-body MSCT provides the clinicians with relevant information to initiate life-saving therapy. Radiologists should use special paediatric protocols that include dose-saving mechanisms to keep the effective dose as low as possible. Further studies are needed to examine and advance dose-saving strategies in MSCT, especially in children.
Assuntos
Traumatismo Múltiplo/diagnóstico por imagem , Doses de Radiação , Tomografia Computadorizada por Raios X , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Imagens de Fantasmas , Estudos Retrospectivos , Software , Imagem Corporal TotalRESUMO
PURPOSE: To assess a novel magnetic resonance imaging (MRI) protocol for quantifying the optic nerve diameter (OND) as a measure of axonal loss in the optic nerve. METHODS: Included in the study was one eye each from 47 subjects, of whom 9 had no eye disease, 16 had preperimetric glaucoma, 11 had a glaucomatous mean visual field defect of <10 dB and 11 of >10 dB. Each subject underwent automated perimetry, scanning laser polarimetry, optic coherence tomography, scanning laser tomography, and ultrafast high-resolution MRI at 3 T. OND was determined 5, 10, and 15 mm behind the eye with a half Fourier-acquired single-shot turbo spin-echo (HASTE)-sequence requiring 1.5 seconds of data acquisition time per slice and providing a spatial resolution of 0.11 mm. A multiple linear regression model was applied to determine correlations (r) among the different techniques. RESULTS: The correlation (r) was <0.37 for OND measurements taken 5 mm behind the eye. At 10 mm behind the eye, r increased to 0.57 and was statistically significant in four out six instances. In the orbital apex 15 mm behind the eye, r reached a maximum of 0.80 and was statistically significant in all instances. OND correlated best with the retinal nerve fiber layer thickness measured by optic coherence tomography. CONCLUSIONS: Retina- or optic nerve head-related surrogate markers for axonal content correlated closely with the OND, although only when it was measured in the orbital apex. High-resolution MRI using an ultrafast HASTE-sequence at 3 T proved useful for OND quantification and may be a valuable asset in future neuroprotection trials.