Identification of ACTH-producing intrathoracic tumors by measuring ACTH levels in aspirated specimens

Three patients with Cushing syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) production underwent direct 22-gauge needle aspiration of bronchial (two cases) and mediastinal (one case) carcinoid tumors. High levels of ACTH were measured in all three tumors. This technique permits absolute identification of an ectopic source of ACTH before surgery.     

Normal hip in children: correlation of US with anatomic and cryomicrotome sections

Full and simultaneous exploitation of features designed to maximize signal-to-noise ratio with the new generation of ultrasound equipment enabled detailed sonographic depiction of the anatomy of the hip and its surroundings. Scanning in familiar planes provided images that are easier to interpret. In addition, correlation of these images with cryomicrotome sections and histochemical studies disclosed several new findings. The articular cartilage of infant hips-composed mostly of water-is anechoic. However, the hyaline cartilage-which contains many vascular channels, columns of cartilage cells, and mesenchymal stroma-appears as alternating hypoechoic or anechoic columns and echogenic columns. The fibrocartilage of the limbus, on the other hand, is echogenic, as are other fibrous tissues. As expected, the points of attachment of the distal aspect of the synovial membrane, the fibrous capsule, and the ligaments in relation to the epiphyseal growth plate, varied with age, as did the characteristics of the cartilaginous structures. Familiarization with the sonographic appearance of normal hip anatomy in subjects of all ages is a first step toward recognition of various pathologic entities of the hip.     

Expression of a functional laminin receptor (alpha 6 beta 1, very late activation antigen-6) on human eosinophils

The mechanisms responsible for the accumulation of eosinophils at sites of allergic and other inflammatory reactions are unknown, but recent studies have implicated both eosinophil and endothelial adhesion molecules in this process. However, less well studied have been the adhesive interactions between eosinophils and the subendothelial basement membrane and interstitial connective tissues. To test the hypothesis that eosinophils might interact with extracellular matrix proteins, we analyzed purified human eosinophils for the expression and function of various beta 1 integrins. Using indirect immunofluorescence and flow cytometry, purified eosinophils from mildly allergic donors were found to consistently express the integrin subunits beta 1 (CD29), alpha 4 (CD49d, very late activation antigen [VLA]-4 alpha), and alpha 6 (CD49f, VLA-6 alpha). No significant expression of the alpha 1, alpha 2, alpha 3, alpha 5, or beta 4 subunits was detected. Platelet contamination of the eosinophil preparations was excluded by light microscopy and by the inability to detect expression of platelet glycoproteins alpha v, CD41b, and CD42b. Immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of eosinophils confirmed the expression of cell-surface beta 1, alpha 4, and alpha 6. Furthermore, eosinophils purified from allergic donors were shown to adhere to plate-bound laminin, but not to type 1 or type 4 collagen. Adhesion to laminin was concentration-dependent, required divalent cations, and was completely and specifically inhibited by the anti-alpha 6 monoclonal antibody (MoAb) GoH3 and by the anti-beta 1 MoAb 33B6. Interestingly, the anti-beta 1 MoAb 18D3 (which like 33B6 blocks eosinophil binding to VCAM-1) did not inhibit eosinophil adhesion to laminin, suggesting that there are functionally distinct epitopes on the beta 1 subunit. Eosinophils purified from 4 healthy, nonallergic donors also showed alpha 6-dependent adhesion to laminin, although these cells adhered less well. These studies establish the expression of alpha 6 beta 1 on human eosinophils and document its function as a laminin receptor. Interaction of eosinophil alpha 6 beta 1 with laminin, eg, in basement membranes, may contribute to the localization of these cells at inflammatory sites in vivo.     

Petrosal sinus sampling for Cushing syndrome: anatomical and technical considerations. Work in progress

ACTH-producing microadenomas of the pituitary gland drain unilaterally into the adjacent cavernous sinus; therefore, petrosal sinus sampling to distinguish pituitary from ectopic-ACTH syndromes must always be performed bilaterally. A negative finding from a unilateral petrosal sinus sample does not exclude the presence of a contralateral ACTH-producing microadenoma. Hemiresection of the pituitary gland based on results of bilateral sampling can be performed if the adenoma is too small to be recognized at surgery. Large pituitary adenomas produce elevated ACTH levels in the petrosal sinuses bilaterally. However, if plain radiographs or CT scans provide unequivocally positive findings in Cushing syndrome (less than 20%), inferior petrosal sinus sampling is not indicated.     

Intramedullary lesions of the pediatric spinal cord: correlation of findings from MR imaging, intraoperative sonography, surgery, and histologic study

Findings of preoperative magnetic resonance (MR) imaging and radiologist-directed intraoperative sonography (IOS) were correlated with surgical and pathologic findings in 11 pediatric patients with intramedullary spinal cord lesions. There were seven gliomas and one each of primitive neuroectodermal tumor, venous vascular malformation, neuroenteric cyst, and active schistosomiasis. MR imaging provided discrete preoperative anatomic localization and excluded multicentric lesions but did not reliably distinguish between solid and cystic lesions. IOS helped (a) define the limits of intramedullary mass before the dura mater was opened and (b) differentiate cystic from solid components. The internal architecture of intramedullary lesions, as shown with MR imaging and sonography, was strikingly similar, allowing discrete correlative localization for biopsy or tissue resection. Gadolinium-enhanced MR imaging and IOS are complementary imaging techniques that should be used in concert for the evaluation and management of intramedullary lesions of the pediatric spinal cord. Both techniques display regions of cord abnormality, but neither definitively characterizes underlying tissue histology.     

Spermaturia and puberty

The pattern of spermaturia in boys at different stages of puberty was investigated. Fractionated 24 hour urine was collected for nine consecutive days from eight boys aged 13-14 years and 10 boys aged 15-17 years. Spermatozoa were detected by microscopic examination of the sediment. Sex characteristics were recorded. Fifty five per cent of all urine samples were positive for sperm and all boys showed spermaturia. A large variation in spermaturia was found between and within boys at the same stage of puberty. Spermaturia was a more common and regular event during early and mid-puberty than in more mature subjects. This indicates that the mechanism of spermaturia in early and late puberty could be different. It is suggested that spermaturia in non-virilised boys could be a result of a spontaneous, continuous flow of spermatozoa to the urethra in contrast with the peristaltic flow during ejaculation occurring at a later stage of puberty.     

Interleukin-1 modulation of cytokine receptors on human neutrophils: in vitro and in vivo studies

Interleukin-1 (IL-1) modulation of cytokine receptors (human IL-1 receptor [hIL-1R], human granulocyte colony-stimulating factor [hG- CSFR], human granulocyte-macrophage CSF receptor [hGM-CSFR], and human tumor necrosis factor receptor [hTNFR]) on human neutrophils was studied both in vitro and in vivo. In vitro, incubation of neutrophils with IL-1 at 37 degrees C for 0.5 or 8 hours caused a reduction of IL-1 binding in a dose-dependent manner, but did not demonstrably affect binding of the other cytokines tested. In vivo, neutrophils from patients with gastrointestinal malignancies who were participating in a clinical trial of recombinant human IL-1 beta (rhIL-1 beta) demonstrated modulation of cytokine receptors in an IL-1 beta dose- and time-dependent manner. At the two highest dose levels of IL-1 beta (0.068 and 0.1 microgram/kg), reduction (> 40%) of G-CSF binding and elevation (twofold to sixfold) of IL-1 binding to neutrophils was observed after 1 hour and 4 to 8 hours, respectively. In addition, IL-1 beta rapidly elevated G-CSF and glucocorticoid levels in plasma. Patients at the lowest dose level (0.002 microgram/kg) had a less dramatic change in these parameters. Further in vitro studies showed that synthetic glucocorticoids and G-CSF synergistically up-modulated IL-1 binding to neutrophils in a dose- and time-dependent manner. Scatchard analysis of binding data showed that this in vitro synergistic modulation was due to an increase in receptor numbers, rather than an increase in binding affinity. In addition, both human umbilical cord blood and bone marrow neutrophils responded to G-CSF and dexamethasone (Dex) with a superadditive increase in IL-1 binding. Therefore, one of mechanisms for IL-1 up-modulation of IL-1R on human neutrophils in vivo was due to the fact that IL-1 rapidly elevates serum levels of G-CSF and glucocorticoids.     

Expression of integrins and examination of their adhesive function in normal and leukemic hematopoietic cells

Adhesion of hematopoietic progenitor cells to marrow-derived adherent cells has been noted for erythroid, myeloid, and lymphoid precursors. In this report, we have characterized very late antigen (VLA) integrin expression on normal CD34+ marrow progenitors, on leukemic cell lines, and on blasts from patients with acute myelogenous or monocytic leukemias. CD34+ progenitor cells expressed the integrin beta 1 chain (CD29), VLA-4 alpha (CD49d), and VLA-5 alpha (CD49e). The myeloid lines KG1 and KG1a also expressed CD49d and CD49e as did the Mo7e megakaryoblastic line. CD29, CD18, and CD11a were also present on each of these cell lines. Only the Mo7e line expressed the cytoadhesins GPIIbIIIa or GPIb. Binding of KG1a to marrow stroma was partially inhibited by antibodies to CD49d and its ligand, vascular cell adhesion molecule (VCAM-1). The majority of leukemic blasts studied expressed CD49d and CD49e as well. Blasts from patients with acute myelomonocytic leukemia consistently bound to stroma at levels greater than 20%, and adhesion to stroma could in some cases be partly inhibited by anti- CD49d. No role for glycosylphosphatidyl-inositol (GPI)-linked structures was demonstrated in these binding assays because the adhesion of leukemic blasts to stroma was not diminished after treatment with phosphatidylinositol-specific phospholipase C (PI-PLC). These studies indicate that CD34+ myeloid progenitors, myeloid leukemic cell lines, and leukemic blasts possess a similar array of VLA integrins. Their functional importance individually or in combination with other mediators of attachment in adhesion, transendothelial migration, and differentiation has yet to be fully elucidated.     

噻芬太尼的主要药效和致依赖性潜力的实验研究

本文研究噻芬太尼的镇痛药效和制动作用,评价其致身体依赖性潜力。小鼠热板法测得噻芬太尼的镇痛作用强度分别为吗啡、芬太尼和埃托啡的3260,22和1.5倍。以瘫痪作为制动指标测得噻芬太尼对大鼠、家兔、狗和猴制动作用强度为埃托啡的2～3倍。小鼠跳跃实验和大鼠饮药液自然戒断实验表明该药具有一定致身体依赖性潜力。大鼠ⅳ快速成瘾实验及长达20周的猴身体依赖性实验则未出现依赖性戒断症状。