Sleep magnetic resonance imaging with electroencephalogram in obstructive sleep apnea syndrome.

OBJECTIVE: To evaluate the mechanism and level of upper airway obstruction in obstructive sleep apnea (OSA) patients during natural sleep, together with synchronous electroencephalogram and respiratory events registration at 3-Tesla magnetic resonance imaging (MRI) platform with high spatial and temporal resolution. STUDY DESIGN: A prospective cohort study of 20 randomly selected OSA patients. METHODS: Fifteen of 20 patients were able to complete spontaneous sleep during MRI. While asleep, dynamic MR images of pharynx were obtained in the midline sagittal view. During the scan, nasal and oral airflow, thoracoabdominal wall effort, and electroencephalogram were synchronously recorded. The physiologic data were retrospectively scored to identify periods of apneas and synchronized with dynamic MR images. RESULTS: In all 15 patients, the site of complete airway obstruction occurred at the retropalatal space. We noticed different positions of the soft palate during apneic events. In seven of 15 patients (47%), the soft palate was attached to the tongue base and moved backward, compressing the airway. In five of 15 patients (33%), the soft palate was detached from the tongue base and solely moved backward, compressing the airway. In three patients (20%), we recorded both mechanisms of complete airway obstruction. In cases with attached soft palate to the tongue base, we noticed significant narrowing of the retrolingual space during apneic events. CONCLUSION: We describe a novel mechanism of obstruction dependent on the position of soft palate. This mechanism might play an important role in selecting candidates for surgery or treatment with hypoglossal nerve stimulation. LEVEL OF EVIDENCE: 2b.

Molecular classification of cutaneous malignant melanoma by gene expression profiling.

The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm. Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities. Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas. Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.

Characterization of platelet activation induced by HLA antibodies associated with alloimmune thrombocytopenia.

The platelet-activating properties of plasma containing multispecific HLA antibodies were studied in plasma from several persons stimulated by platelet or red blood cell transfusion or by pregnancy. Antibodies were characterized by their lymphocytotoxic effects and by a monoclonal antibody antigen--capture enzyme-linked immunoassay. Plasma from each patient induced dose-dependent aggregation and release of adenosine triphosphate with antigen-positive platelet-rich plasma. Plasma from three patients induced normal aggregation and adenosine triphosphate release with platelet-rich plasma from donors who had taken platelet inhibiting medications (e.g. aspirin, piroxicam). In contrast, these platelets failed to release adenosine triphosphate when stimulated with 5 mumol/L adenosine diphosphate. Platelets were fully activated when saturated with HLA antibodies from one patient, although little or no stimulation was observed at 50% saturation suggesting that additional plasma cofactors and/or a threshold of bound antibody were required for activation. With a murine monoclonal antibody specific for P-selectin and antimurine immunoglobulin G labeled with iodine 125, plasma from each patient was found to induce P-selectin expression that was approximately 50% of that induced by 0.2 U/ml thrombin. Expression on platelets of P-selectin induced by plasma from one patient was independent of whether the donor had taken aspirin. Purified immunoglobulin G from this same patient stimulated platelet activation, as did the patient's serum, but no activation was observed with F(ab')2 fragments prepared from the immunoglobulin G. These studies demonstrate that HLA antibodies (1) mediate expression of P-selectin on the platelet surface, (2) are as potent as thrombin in activating platelets previously exposed to antiinflammatory agents, and (3) require an intact Fc domain to activate platelets.