Granulomatous mediastinal adenopathy: can endoscopic ultrasound-guided fine-needle aspiration differentiate between tuberculosis and sarcoidosis?

BACKGROUND AND STUDY AIMS: Mediastinal lymphadenopathy may indicate diseases such as tuberculosis or sarcoidosis, and it is often difficult to establish a diagnosis when standard medical work-up is inconclusive. In this study we investigated the diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the differentiation between tuberculosis and sarcoidosis. PATIENTS AND METHODS: In this prospective study, 72 consecutive patients with mediastinal lymphadenopathy, negative endoscopic investigations including bronchoscopic procedures, and no radiological evidence of lung cancer or other malignancies on computed tomography were enrolled. EUS-FNA and subsequent cytology, microscopy for acid-fast bacilli, and culture were performed. At least 12 months' follow-up including further investigations was included to exclude tuberculosis. RESULTS: Adequate samples were obtained from 71/72 patients (36 male; mean age 50.2 years). No complications occurred. The final diagnosis included 30 cases of sarcoidosis, 28 of tuberculosis, four malignancies, one abscess, and nine benign lymphadenopathies. The size of lymph nodes on EUS varied from 0.5 cm to 4.2 cm. Tuberculosis nodes were significantly smaller than those in sarcoidosis. Unrelated nodes were significantly smaller than in either tuberculosis or sarcoidosis. The sensitivity, specificity, and positive and negative predictive values of EUS - FNA for tuberculosis were 86 %, 100 %, 100 %, and 91 %, respectively; those for sarcoidosis were 100 %, 93 %, 91 %, and 100 %, respectively. For culture of tuberculosis, they were 71 %, 100 %, 100 %, and 84 %, respectively. EUS - FNA led to a definite diagnosis in 64/72 cases (89 %) that had not been previously diagnosed by routine methods. CONCLUSION: EUS - FNA offers a high diagnostic yield for the differential diagnosis of tuberculosis and sarcoidosis that have not been diagnosed by conventional methods.

Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders.

Disrupted In Schizophrenia 1 (DISC1) was identified as a potential susceptibility gene for schizophrenia due to its disruption by a balanced t(1;11) (q42;q14) translocation, which has been shown to cosegregate with major psychiatric disease in a large Scottish family. We have demonstrated that DISC1 exists in a neurodevelopmentally regulated protein complex with Nudel. The complex is abundant at E17 and in early postnatal life but is greatly reduced in the adult. Nudel has previously been shown to bind Lis1, a gene underlying lissencephaly in humans. Critically, we show that the predicted peptide product resulting from the Scottish translocation removes the interaction domain for Nudel. DISC1 interacts with Nudel through a leucine zipper domain and binds to a novel DISC1-interaction domain on Nudel, which is independent from the Lis1 binding site. We show that Nudel is able to act as a bridge between DISC1 and Lis1 to allow formation of a trimolecular complex. Nudel has been implicated to play a role in neuronal migration, together with the developmental variation in the abundance of the DISC1-Nudel complex, may implicate a defective DISC1-Nudel complex as a neurodevelopmental cause of schizophrenia.

Visual and semiquantitative analysis of 18F-fluorodeoxyglucose positron emission tomography using a partial-ring tomograph without attenuation correction to differentiate benign and malignant pulmonary nodules.

OBJECTIVE: Many studies have reported the use of attenuation-corrected positron emission tomography with 18F-fluorodeoxyglucose (FDG PET) with full-ring tomographs to differentiate between benign and malignant pulmonary nodules. We sought to evaluate FDG PET using a partial-ring tomograph without attenuation correction. METHODS: A retrospective review of PET images from 77 patients (range 38-84 years of age) with proven benign or malignant pulmonary nodules was undertaken. All images were obtained using a Siemens/CTI ECAT ART tomograph, without attenuation correction, after 185 MBq 18F-FDG was injected. Images were visually graded on a 5-point scale from "definitely malignant" to "definitely benign," and lesion-to-background (LB) ratios were calculated using region of interest analysis. Visual and semiquantitative analyses were compared using receiver operating characteristic analysis. RESULTS: Twenty lesions were benign and 57 were malignant. The mean LB ratio for benign lesions was 1.5 (range 1.0-5.7) and for malignant lesions 5.7 (range 1.2-14.1) (p < 0.001). The area under the ROC curve for LB ratio analysis was 0.95, and for visual analysis 0.91 (p = 0.39). The optimal cut-off ratio with LB ratio analysis was 1.8, giving a sensitivity of 95% and a specificity of 85%. For lesions thought to be "definitely malignant" on visual analysis, the sensitivity was 93% and the specificity 85%. Three proven infective lesions were rated as malignant by both techniques (LB ratio 2.6-5.7). CONCLUSIONS: FDG PET without attenuation correction is accurate for differentiating between benign and malignant lung nodules. Results using simple LB ratios without attenuation correction compare favourably with the published sensitivity and specificity for standard uptake ratios. Visual analysis is equally accurate.

Two cases of Wegener's granulomatosis involving the pituitary.

We describe two patients with Wegener's granulomatosis involving the pituitary. The diagnosis of Wegener's granulomatosis was inferred from the histological appearance of biopsy tissue and the presence of anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution in the first case, in which disease remained confined to the pituitary, causing anterior and posterior pituitary dysfunction. In the second case the diagnosis was made by the progressive involvement of other organ systems, compatible histology and the presence of anti-neutrophil cytoplasmic antibodies with cytoplasmic distribution. In neither patient did posterior pituitary dysfunction respond to immunosuppressive therapy, despite remission of other features of systemic vasculitis. Panhypopituitarism in association with isolated pituitary Wegener's granulomatosis has not previously been described.