RESUMO
Pituitary development depends on a complex cascade of interacting transcription factors and signaling molecules. Lesions in this cascade lead to isolated or combined pituitary hormone deficiency (CPHD). The aim of this study was to identify copy number variants (CNVs) in genes known to cause CPHD and to determine their structure. We analyzed 70 CPHD patients from 64 families. Deletions were found in three Turkish families and one family from northern Iraq. In one family we identified a 4.96 kb deletion that comprises the first two exons of POU1F1. In three families a homozygous 15.9 kb deletion including complete PROP1 was discovered. Breakpoints map within highly homologous AluY sequences. Haplotype analysis revealed a shared haplotype of 350 kb among PROP1 deletion carriers. For the first time we were able to assign the boundaries of a previously reported PROP1 deletion. This gross deletion shows strong evidence to originate from a common ancestor in patients with Kurdish descent. No CNVs within LHX3, LHX4, HESX1, GH1 and GHRHR were found. Our data prove multiplex ligation-dependent probe amplification to be a valuable tool for the detection of CNVs as cause of pituitary insufficiencies and should be considered as an analytical method particularly in Kurdish patients.
Assuntos
Haplótipos , Proteínas de Homeodomínio/genética , Hipopituitarismo/genética , Deleção de Sequência , Fator de Transcrição Pit-1/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , LinhagemRESUMO
A 37-year-old female patient with systemic mastocytosis who was admitted with severe unexplained bleeding symptoms is studied. Laboratory procedures established the diagnosis of a patient-derived-heparin-like anticoagulant as a very rare hemostatic abnormality predisposing to bleeding. The patient died from refractory disease despite therapy with protamine, initiation of chemotherapy, and supportive measures. The case illustrates the clinical presentation and diagnosis of heparin-like anticoagulants. Etiology, pathophysiology, and therapeutic options are discussed.
Assuntos
Anticoagulantes/sangue , Hemorragia/sangue , Hemorragia/etiologia , Heparina/sangue , Mastocitose Sistêmica/sangue , Mastocitose Sistêmica/complicações , Adulto , Medula Óssea/patologia , Evolução Fatal , Feminino , Humanos , Mastócitos/patologia , Mastocitose Sistêmica/patologiaRESUMO
OBJECTIVE: Esophagectomy for esophageal cancer is associated with substantial postoperative morbidity as a result of infectious complications. In a prior phase II study, granulocyte colony-stimulating factor (G-CSF) was shown to improve leukocyte function and to reduce infection rates after esophagectomy. The aim of the current randomized, placebo-controlled, multicenter phase III trial was to investigate the clinical efficacy of perioperative G-CSF administration in reducing infection and mortality after esophagectomy for esophageal cancer. PATIENTS AND METHODS: One hundred fifty five patients with resectable esophageal cancer were randomly assigned to perioperative G-CSF at standard doses (77 patients) or placebo (76 patients), administered from 2 days before until day 7 after esophagectomy. The G-CSF and placebo groups were comparable as regards age, gender, risk, cancer stage, frequency of neoadjuvant radiochemotherapy, and type of esophagectomy (transthoracic or transhiatal esophageal resection). RESULTS: Of 155 randomized patients, 153 were eligible for the intention-to-treat analysis. The rate of infection occurring within the first 10 days after esophagectomy was 43.4% (confidence interval 32.8-55.9%) in the placebo and 44.2% (confidence interval 32.1-55.3%) in the G-CSF group (P = 0.927). 30-day mortality amounted to 5.2% in the G-CSF group versus 5.3% in the placebo group (P = 0.985). Similar results were found in the per-protocol analysis. CONCLUSION: Perioperative administration of G-CSF failed to reduce postoperative morbidity, infection rate, or mortality in patients with esophageal cancer who underwent esophagectomy.
Assuntos
Anti-Infecciosos/administração & dosagem , Neoplasias Esofágicas/cirurgia , Esofagectomia , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Pré-Medicação , Adulto , Idoso , Método Duplo-Cego , Feminino , Filgrastim , Humanos , Infecções/etiologia , Masculino , Mediastinite/etiologia , Pessoa de Meia-Idade , Assistência Perioperatória , Pneumonia/etiologia , Proteínas Recombinantes , Fatores de Risco , Sepse/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Infecções Urinárias/etiologiaRESUMO
Clinically inapparent adrenal masses are incidentally detected after imaging studies conducted for reasons other than the evaluation of the adrenal glands. They have frequently been referred to as adrenal incidentalomas. In preparation for a National Institutes of Health State-of-the-Science Conference on this topic, extensive literature research, including Medline, BIOSIS, and Embase between 1966 and July 2002, as well as references of published metaanalyses and selected review articles identified more than 5400 citations. Based on 699 articles that were retrieved for further examination, we provide a comprehensive update of the diagnostic and therapeutic approaches focusing on endocrine and radiological features as well as surgical options. In addition, we present recent developments in the discovery of tumor markers, endocrine testing for subclinical disease including autonomous glucocorticoid hypersecretion and silent pheochromocytoma, novel imaging techniques, and minimally invasive surgery. Based on the statements of the conference, the available literature, and ongoing studies, our aim is to provide practical recommendations for the management of this common entity and to highlight areas for future studies and research.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/terapia , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/terapia , Neoplasias das Glândulas Suprarrenais/epidemiologia , Glândulas Suprarrenais/patologia , Adrenalectomia , Aldosterona/metabolismo , Biomarcadores Tumorais , Biópsia por Agulha Fina , Diagnóstico por Imagem , Hormônios Esteroides Gonadais/metabolismo , Hormônios/análise , Humanos , Hidrocortisona/metabolismo , MEDLINE , Metástase Neoplásica , Feocromocitoma/diagnóstico , Feocromocitoma/terapiaRESUMO
The hypothalamic-pituitary-adrenal (HPA) axis is integrated in the human stress system and controls the metabolism of many cell systems in the body. Therefore, hypofunction or hyperfunction of the HPA axis potentially threatens the life of the whole organism. Noncontrolled overproduction of its key regulators, CRH and ACTH, causes dysfunction of the stress system. Ectopic secretion of these compounds may be part of extraadrenal paraneoplastic syndromes caused by various benign or malignant tumors. However, ectopic ACTH and CRH may originate from the adrenal itself. A local CRH/ACTH system exists in the normal human adrenal medulla. Overproduction of CRH and ACTH has been documented in pheochromocytomas causing Cushing's syndrome. Finally, ectopic production of ACTH causing Cushing's syndrome has also been demonstrated in adrenocortical cells. This suggests a marked plasticity within the HPA axis and the neuroendocrine cell system.