HDL and endothelial protection

High-density lipoproteins (HDLs) represent a family of particles characterized by the presence of apolipoprotein A-I (apoA-I) and by their ability to transport cholesterol from peripheral tissues back to the liver. In addition to this function, HDLs display pleiotropic effects including antioxidant, anti-apoptotic, anti-inflammatory, anti-thrombotic or anti-proteolytic properties that account for their protective action on endothelial cells. Vasodilatation via production of nitric oxide is also a hallmark of HDL action on endothelial cells. Endothelial cells express receptors for apoA-I and HDLs that mediate intracellular signalling and potentially participate in the internalization of these particles. In this review, we will detail the different effects of HDLs on the endothelium in normal and pathological conditions with a particular focus on the potential use of HDL therapy to restore endothelial function and integrity.     

A 15q13.3 microdeletion segregating with autism

Autism and mental retardation (MR) show high rates of comorbidity and potentially share genetic risk factors. In this study, a rare ∼2 Mb microdeletion involving chromosome band 15q13.3 was detected in a multiplex autism family. This genomic loss lies between distal break points of the Prader–Willi/Angelman syndrome locus and was first described in association with MR and epilepsy. Together with recent studies that have also implicated this genomic imbalance in schizophrenia, our data indicate that this CNV shows considerable phenotypic variability. Further studies should aim to characterise the precise phenotypic range of this CNV and may lead to the discovery of genetic or environmental modifiers.     

Craniofacial mucormycosis: assessment with CT

Computed tomographic (CT) scans of ten patients with rhinocerebral mucormycosis were reviewed. Early paranasal sinus involvement appeared as mucosal thickening on CT scans, usually without air/fluid levels. Recognition as mucormycosis was facilitated by knowledge of the clinical setting or by identification of invasive disease. Evidence of bone destruction on CT scans was seen in only two patients, was a late finding, and usually was absent despite deep extension of disease beyond the bony confines of the paranasal sinus. Five cases had intracranial involvement, either as fungal abscess or infarction. Intracranial mucormycosis usually involved the base of the brain and cerebellum following invasion of the infratemporal fossa or orbit. Intracerebral fungal abscess appeared as low-density masses on CT scans, with variable peripheral enhancement and little surrounding vasogenic edema. Identification of a rim of spared cortex was useful in distinguishing infection from bland infarct. Serial CT scans were also useful in assessing response to hyperbaric oxygen treatment, surgery, and chemotherapy.     

Recurrent postoperative sciatica: evaluation with MR imaging and enhanced CT

Magnetic resonance (MR) imaging and computed tomography enhanced with intravenous iodine injection (ECT) were prospectively compared in 80 patients in the diagnosis of recurrent postoperative sciatica. Diagnostic accuracy was determined with surgical verification. Isolated fibrosis was considered a contraindication to surgery. A decision to operate was made in 56 of the 80 patients on the basis of MR imaging findings; in 21 of the 56, the decision was also made on the basis of ECT findings. Of the 80 patients, 45 underwent surgery, In all but one of these patients, the diagnosis made on the basis of MR imaging findings was confirmed with surgical analysis. The only surgical finding that did not agree with MR imaging findings was a calcification of the common posterior ligament. The 21 diagnoses of disk herniation based on ECT findings were confirmed surgically, but among the 24 diagnoses of fibrosis made with the help of ECT, there were actually 19 recurrent herniations, four herniations with fibrosis, and one herniation at the level above the previously resected disk. MR imaging seems to be the investigation of choice in diagnosing the cause of recurrent postoperative sciatica.     

Ultra-high-speed teleradiology with ISDN technology

A solid-state, personal computer-based, image digitization and transmission system was developed that uses integrated services digital network (ISDN), a technology under development for ultra-high-speed data transmission over normal phone lines. Thousands of images have been transmitted to a site more than 15 miles away, with data rates exceeding 56,000 bits or 7,000 bytes (1 byte = 8 bits) per second with nearly perfect accuracy. Present modification of the system hardware and software should increase the data rate to 128,000 bits, or 16,000 bytes, per second. With this rate of transmission, remote radiologic image transmission should become a practical, routinely available diagnostic tool.     

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.