Optimal combination of estimating equations in the analysis of multilevel nested correlated data.

Multilevel nested, correlated data often arise in biomedical research. Examples include teeth nested within quadrants in a mouth or students nested within classrooms in schools. In some settings, cluster sizes may be large relative to the number of independent clusters and the degree of correlation may vary across clusters. When cluster sizes are large, fitting marginal regression models using Generalized Estimating Equations with flexible correlation structures that reflect the nested structure may fail to converge and result in unstable covariance estimates. Also, the use of patterned, nested working correlation structures may not be efficient when correlation varies across clusters. This paper describes a flexible marginal regression modeling approach based on an optimal combination of estimating equations. Particular within-cluster and between-cluster data contrasts are used without specification of the working covariance structure and without estimation of covariance parameters. The method involves estimation of the covariance matrix only for the vector of component estimating equations (which is typically of small dimension) rather than the covariance matrix of the observations within a cluster (which may be of large dimension). In settings where the number of clusters is large relative to the cluster size, the method is stable and is highly efficient, while maintaining appropriate coverage levels. Performance of the method is investigated with simulation studies and an application to a periodontal study.

Giant intracranial aneurysm and fibromuscular dysplasia in an adolescent with alpha 1-antitrypsin deficiency.

Recent studies have suggested that a deficiency of alpha 1-antitrypsin may be a genetic risk factor for the development of intracranial aneurysms and arterial fibromuscular dysplasia. The authors report a 16-year-old girl with a history of lung disease who suffered a cerebral hemorrhage due to the rupture of a giant intracranial aneurysm arising from the middle cerebral artery. This fusiform aneurysm was associated with fibromuscular dysplasia of the intimal type. She was found to have an unusual alpha 1-antitrypsin deficiency (PiMP phenotype). This case provides further evidence of an underlying arteriopathy in alpha 1-antitrypsin deficiency.

Medical and surgical management of intracranial aneurysms.

OBJECTIVE: To examine the medical and surgical aspects of intracranial aneurysms, including the pathogenesis, clinical manifestations, management of subarachnoid hemorrhage (SAH), and indications for surgical intervention. DESIGN: This review presents the classification of intracranial aneurysms, defines specific aneurysms, and analyzes the Mayo Clinic experience with surgical treatment of cerebral aneurysms. MATERIAL AND METHODS: Intracranial aneurysms are classified by cause, size, site, and shape. The clinical grading systems for SAH, the most common manifestation, are as follows: modified Botterell, Hunt and Hess, and World Federation of Neurological Surgeons. Surgical options are direct clipping, interventional neuroradiologic treatment, proximal ligation or trapping of aneurysms, and wrapping or coating of aneurysms. Although the timing of surgical intervention after SAH is controversial, it should be based on the clinical grade, site of the aneurysm, and patient's medical condition. RESULTS: The frequency of intracranial aneurysms is estimated to be 1 to 8% in the general population, and 90% of patients have SAH. After SAH, 8 to 60% of patients die before they get to a hospital. After hospitalization, the mortality rate is 37%, severe disability is 17%, and outcome is favorable in 47%. The current trend for surgical treatment is early after SAH. The Mayo Clinic experience with 1,947 patients who underwent surgical treatment because of aneurysmal SAH or for aneurysmal repair between 1969 and 1990 is as follows: 1,445 had an excellent outcome, 231 had a good outcome, 171 had a poor outcome, and 100 died. CONCLUSION: Aggressive management can be beneficial for many patients with severe neurologic injury after SAH by preventing rerupture of the aneurysm, attenuating the severity and sequelae of vasospasm, and decreasing the surgical complications.

Intraventricular infusion of HBGF-2 promotes cerebral angiogenesis in Wistar rat.

The angiogenic effects of chronic intraventricular infusion of basic fibroblastic growth factor (HBGF-2) were assessed in the Wistar rat cerebral cortex. HBGF-2 increased both capillary density and area of perfused vasculature without altering capillary diameters in periventricular cortex adjacent to the site of infusion. Although it has been demonstrated that growth factors can cause brain endothelial proliferation in vitro, this is the first report of in vivo cerebral angiogenesis.