Narcolepsy and psychopathology: is there an association?

BACKGROUND: It is widely believed that patients with narcolepsy show high rates of associated psychiatric disturbance, especially schizophrenia and depression. However, surveys have produced conflicting findings and have not addressed the potential confounding effects of stimulant drug treatment. METHOD: Forty-five patients with narcolepsy attending a sleep disorder clinic and 50 matched normal controls underwent structured psychiatric interview. Using a 'lifetime' approach, psychiatric symptoms and diagnoses were established for both groups. RESULTS: Four of the narcolepsy patients but none of the controls had experienced psychotic symptoms. All four patients were taking amphetamines, and the symptoms resolved when the dose was lowered or treatment was changed to modafinil. The lifetime frequency of various depressive syndromes did not differ significantly between the groups. CONCLUSIONS: Contrary to previous claims this study found little to suggest that narcolepsy is associated with schizophrenia. Nor, despite its serious social and occupational consequences, does narcolepsy appear to be associated with an increased frequency of diagnosable depressive disorders.     

Sphenoid sinus mucocele--rupture causing brainstem inflammation and stroke

BACKGROUND: Posterior rupture of a sphenoid sinus mucocele is a rare cause of brainstem injury. METHODS: Case report. RESULTS: A healthy young woman with a history of prior surgical excision of nasal polyps presented with a headache and evolving neurologic symptoms. The clinical presentation and imaging studies were consistent with a posterior rupture of a large sphenoid mucocele with subsequent inflammatory changes in the brainstem and evidence of brainstem stroke. Relatively rapid recovery coincided temporally with the resolution of local inflammation. Longer-term recovery continued over months, as expected following stroke. CONCLUSIONS: Posterior rupture of a sphenoid sinus mucocele may cause brainstem injury by multiple mechanisms.     

Identification and characterization of a low-affinity granulocyte- macrophage colony-stimulating factor receptor on primary and cultured human melanoma cells

Hematopoietic growth factor receptors are present on cells of normal nonhematopoietic tissues such as endothelium and placenta. We previously demonstrated functional human granulocyte-macrophage colony- stimulating factor (GM-CSF) receptors on small cell carcinoma of the lung cell lines, and others have reported that certain solid tumor cell lines respond to GM-CSF in clonogenic assays. In the current study, we examine human melanoma cell lines and fresh specimens of melanoma to determine whether they have functional GM-CSF receptors. Scatchard analyses of 125I-GM-CSF equilibrium binding to melanoma cell lines showed a mean of 542 +/- 67 sites per cell with a kd of 0.72 +/- 0.14 nmol/L. Cross-linking studies in the melanoma cell line, M14, showed a major GM-CSF receptor species of 84,000 daltons. Under the conditions tested, the M14 cells did not have a proliferative response to GM-CSF in vitro, nor was any induction of primary response genes detected by Northern analysis in response to GM-CSF. Studies to determine internal translocation of the receptor-ligand complex indicated less than 10% of the 125I-GM-CSF internalized was specifically bound to receptors. Primary melanoma cells from five surgical specimens had GM-CSF receptors; Scatchard analysis was performed on one sample, showing 555 sites/cell with a kd of 0.23 nmol/L. These results indicate that human tumor cells may express a low-affinity GM-CSF receptor protein that localizes to the cell surface and binds ligand, but lacks functional components or accessory factors needed to transduce a signal.     

Persistence, reproducibility, and cost-effectiveness of an intervention to improve the quality of osteoporosis care after a fracture of the wrist: results of a controlled trial

INTRODUCTION: Older patients with fragility fractures are not commonly tested or treated for osteoporosis. Compared to usual care, a previously reported intervention led to 30% absolute increases in osteoporosis treatment within 6 months of wrist fracture. Our objective was to examine longer-term outcomes, reproducibility, and cost-effectiveness of this intervention. METHODS: We conducted an extended analysis of a non-randomized controlled trial with blinded ascertainment of outcomes that compared a multifaceted intervention to usual care controls. Patients >50 years with a wrist fracture treated in two Emergency Departments in the province of Alberta, Canada were included; those already treated for osteoporosis were excluded. Overall, 102 patients participated in this study (55 intervention and 47 controls; median age: 66 years; 78% were women). The interventions consisted of faxed physician reminders that contained osteoporosis treatment guidelines endorsed by opinion leaders and patient counseling. Controls received usual care; at 6-months post-fracture, when the original trial was completed, all controls were crossed-over to intervention. The main outcomes were rates of osteoporosis testing and treatment within 6 months (original study) and 1 year (delayed intervention) of fracture, and 1-year persistence with treatments started. From the perspective of the healthcare payer, the cost-effectiveness (using a Markov decision-analytic model) of the intervention was compared with usual care over a lifetime horizon. RESULTS: Overall, 40% of the intervention patients (vs. 10% of the controls) started treatment within 6 months post-fracture, and 82% (95%CI: 67-96%) had persisted with it at 1-year post-fracture. Delaying the intervention to controls for 6 months still led to equivalent rates of bone mineral density (BMD) testing (64 vs. 60% in the original study; p = 0.72) and osteoporosis treatment (43 vs. 40%; p = 0.77) as previously reported. Compared with usual care, the intervention strategy was dominant - per patient, it led to a $13 Canadian (U.S. $9) cost savings and a gain of 0.012 quality-adjusted life years. Base-case results were most sensitive to assumptions about treatment cost; for example, a 50% increase in the price of osteoporosis medication led to an incremental cost-effectiveness ratio of $24,250 Canadian (U.S. $17,218) per quality-adjusted life year gained. CONCLUSIONS: A pragmatic intervention directed at patients and physicians led to substantial improvements in osteoporosis treatment, even when delivered 6-months post-fracture. From the healthcare payer's perspective, the intervention appears to have led to both cost-savings and gains in life expectancy.     

Adherence of L1210 murine leukemia cells to sephacryl- aminopropylcobalamin beads treated with transcobalamin-II

Sephacryl beads containing an immobilized aminopropylcobalamin- transcobalamin-II complex serve as foci for the adherence of L1210 murine leukemia cells. Bead-cell interaction does not occur when (A) nonderivatized beads are used; (B) transcobalamin-II is omitted or presaturated with cyanocobalamin in the preparation of the bead complex; (C) intrinsic factor replaces transcobalamin-II; and (D) the complex is removed from beads by photolysis. These observations suggest that adherence results from the ability of transcobalamin-II to form a bridge between immobilized cobalamin on the bead and receptors in the plasma membrane of the cell.