Inpatient statin use predicts improved ischemic stroke discharge disposition.

OBJECTIVE: To determine whether statin use is associated with improved discharge disposition after ischemic stroke. METHODS: We used generalized ordinal logistic regression to analyze discharge disposition among 12,689 patients with ischemic stroke over a 7-year period at 17 hospitals in an integrated care delivery system. We also analyzed treatment patterns by hospital to control for the possibility of confounding at the individual patient level. RESULTS: Statin users before and during stroke hospitalization were more likely to have a good discharge outcome (odds ratio [OR] for discharge to home = 1.38, 95% confidence interval [CI] 1.25-1.52, p < 0.001; OR for discharge to home or institution = 2.08, 95% CI 1.72-2.51, p < 0.001). Patients who underwent statin withdrawal were less likely to have a good discharge outcome (OR for discharge to home = 0.77, 95% CI 0.63-0.94, p = 0.012; OR for discharge to home or institution = 0.43, 95% CI 0.33-0.55, p < 0.001). In grouped-treatment analysis, an instrumental variable method using treatment patterns by hospital, higher probability of inpatient statin use predicted a higher likelihood of discharge to home (OR = 2.56, 95% CI 1.71-3.85, p < 0.001). In last prior treatment analysis, a novel instrumental variable method, patients with a higher probability of statin use were more likely to have a good discharge outcome (OR for each better level of ordinal discharge outcome = 1.19, 95% CI 1.09-1.30, p = 0.001). CONCLUSIONS: Statin use is strongly associated with improved discharge disposition after ischemic stroke.

Minimum incidence of primary cervical dystonia in a multiethnic health care population.

BACKGROUND: The two existing estimates of the incidence of primary cervical dystonia were based on observations in relatively ethnically homogeneous populations of European descent. OBJECTIVE: To estimate the minimum incidence of primary cervical dystonia in the multiethnic membership of a health maintenance organization in Northern California. METHODS: Using a combination of electronic medical records followed by medical chart reviews, we identified incident cases of cervical dystonia first diagnosed between 1997 and 1999. RESULTS: We identified 66 incident cases of cervical dystonia from 8.2 million person-years of observation. The minimum estimate of the incidence of cervical dystonia in this population is 0.80 per 100,000 person-years. Ethnicity-specific incidence rates were calculated for individuals over age 30. Incidence was higher in white individuals (1.23 per 100,000 person-years) than in persons of other races (0.15 per 100,000 person-years, p < 0.0001). The minimum estimated incidence was 2.5 times higher in women than in men (1.14 vs 0.45 per 100,000 person-years, p = 0.0005). The average age at diagnosis was higher in women (56 years) than in men (45 years, p = 0.0004). There was no significant difference in reported symptom duration prior to diagnosis between women and men (3.9 vs 5.3 years). CONCLUSION: The estimated incidence of diagnosed cervical dystonia among white individuals in this Northern Californian population is similar to previous estimates in more ethnically homogeneous populations of largely European descent. The incidence in other races, including Hispanic, Asian, and black appears to be significantly lower. The incidence is also higher in women than in men.

Clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy.

OBJECTIVE: To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM. METHODS: Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected and 28 unaffected members of 16 unrelated families in which 2 or more blood relatives developed an IIM. In addition, findings in patients with familial IIM were compared with those in 181 patients with sporadic IIM. The families included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with other siblings or relatives with polymyositis or dermatomyositis, and 2 families with inclusion body myositis. RESULTS: The clinical features of familial IIM were similar to those of sporadic IIM, although the frequency of myositis-specific autoantibodies was lower in familial than in sporadic IIM. DRB1*0301 was a common genetic risk factor for familial and sporadic IIM, but contributed less to the genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic IIM). Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P = 0.002). CONCLUSION: These findings emphasize that 1) familial muscle weakness is not always due to inherited metabolic defects or dystrophies, but may be the result of the development of IIM in several members of the same family, and 2) multiple genetic factors are likely important in the etiology and disease expression of familial IIM, as is also the case for sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial IIM.

Automated determination of excitatory amino acid neurotoxicity in cortical culture.

We used a commercially available robotic laboratory workstation to quantitatively study excitotoxic neuronal injury in cell culture. A Beckman Instruments Biomek 1000 was programmed to perform both timed exposures to excitatory amino acid agonists, and kinetic assay of the resultant efflux of lactic dehydrogenase from damaged neurons, using 96-well culture plates. Examination of homocysteate neurotoxicity utilizing this automated method produced results similar to those obtained earlier using manual techniques. The method described here may facilitate the characterization of neurotoxic agonist or antagonist activity.

Functional recovery. A major risk factor for the development of postpoliomyelitis muscular atrophy.

A retrospective study was undertaken to identify potential risk factors for the development of progressive postpoliomyelitis muscular atrophy (PPMA). Patients with PPMA (n = 57) were compared with patients with a history of poliomyelitis but without a history of progressive weakness (n = 49). Patients who later developed PPMA had histories of more widespread acute paralysis, but relatively greater functional recovery. They were less disabled, and reported higher recent activity levels. Seventy-nine percent of the total variance between the PPMA and control groups could be accounted for by recovery alone (ie, severity minus disability). Functional recovery is generally attributed to reinnervation of sarcomeres by collateral sprouting from surviving lower motor neurons. Since degree of recovery predicts the risk of developing PPMA, our findings suggest that enlarged motor units may carry an increased susceptibility for dysfunction and/or degeneration.

Synaptic junctional glycoconjugates from chick brain. Glycoprotein identification and carbohydrate composition.

Forebrains from day-old chicks were homogenized and fractionated by differential sedimentation and density gradient centrifugation to yield subcellular fractions. The synaptosomal plasma membrane fraction was further treated with Triton X-100 to yield subsynaptic membrane fractions including synaptic junctions. Glycoproteins from these subsynaptic membrane fractions were identified after separation by SDS-polyacrylamide gel electrophoresis by incubating the gel slabs with radioiodinated concanavalin A. Two lectin-binding proteins were discerned in the synaptic junction fraction while none were observed in the Triton-soluble portion of the synaptic plasma membrane. The carbohydrate content of the glycoproteins from each subcellular fraction was quantitated after methanolysis and derivatization as o-methyl-trifluoroacetyl analogs by gas-liquid chromatography. The lowest concentration of glycoprotein sugars was found in the synaptic junction, mitochondrial, and soluble fractions while the greatest concentration was found in the myelin, light-synaptic plasma membrane, and the Triton-soluble portion of the synaptic plasma membrane. Of the subcellular fractions, the synaptic junction contained the highest porportion of mannose and lowest proportion of sialic acid. Moreover, this fraction's content of galactose and N-acetylglucosamine, relative to mannose was the lowest while its content of fucose was low. The oligosaccharide chains extending into the synaptic cleft therefore are predominantly of the "neutral, mannose-rich" type and are attached to a limited number of high-molecular-weight glycoproteins.

Incorporation of radiolabelled sugars into synaptic junctional macromolecules from chick brain.

Individual radiolabelled sugars ([1-14C]-L-fucose, [U-14C]-D-galactose, [U-14C]-D-mannose, [U-14C]-D-glucose and [U-14C]-D-glucosamine) were injected intraventricularly into the forebrains of day-old chickens, and the relative incorporation, after 6 hr, into the glycoprotein sugars, aglycosyl protein, glycolipid sugars and aglycosyl lipid assessed. In addition, the relative total and specific activities of the individual glycoprotein sugars was also determined. Exclusive labelling of glycoprotein sugars (and of the fucose within these oligosaccharides) using fucose as precursor was confirmed, while optimal labelling of glycolipid sugars was achieved using the precursor mannose. Galactose, mannose, glucose and glucosamine were converted to varying degrees to other sugars and non-sugar precursors prior to incorporation. Glucosamine gave rise to the most even distribution of radioactivity among the glycoprotein sugar residues. The highest relative specific activities of the glycoprotein oligosaccharides were achieved using fucose and glucosamine as precursors.

Isolation of synaptic junction-enriched fraction from the forebrain of day-old chickens. Preparation and characterization of chick forebrain subcellular fractions.

Synaptosomal plasma membrane (SPM) and other subcellular fractions were isolated from the forebrain of 1-day-old chickens by a procedure based on that of Davis and Bloom (16) and Cotman and Taylor (13). The procedure involves the centrifugation through a discontinuous sucrose gradient of a crude synaptosomal-mitochondrial fraction which has been lysed and weighed with iodonitrotetrazolium. SPM isolated by this method contains only small amounts of lysosomal or mitochondrial membranes and is practically devoid of contaminating microsomal membranes, as estimated by enzyme marker assays. The purity of chick-brain SPM prepared by this method is compared to the purity of chick-brain fractions obtained by two other laboratories, using different methods (4, 59). The SPM were extracted with Triton X-100 and all fractions solubilized in sodium dodecyl sulfate (sds). The delipidated proteins of all fractions were subjected to SDS-polyacrylamide electrophoresis on slab gels and stained for protein. A distinct difference was observed between the patterns given by the Triton-soluble and -insoluble fractions. Electron microscopy of the synaptic junction fraction showed numerous junctional complexes.

Host response to Treponema pallidum infection. I. Quantitative changes of lipids in rabbit organs.

Levels of phospholipids, glycolipids and cardiolipin were determined in various organs of Treponema pallidum-infected rabbits. The phospholipid levels on the second week of infection decreased significantly in the spleen but remained unchanged in other organs. During the same time, glycolipids decreased significantly in both kidney and heart. 3 days after infection, a brief but significant increase of cardiolipin in the spleen was observed. Heat-killed T. pallidum but not Treponema reiteri caused a similar effect. The possible implication of these changes in the immunopathology of syphilis is discussed.

The preparation of silica gel thin layers with a new apparatus.

An apparatus for the preparation of uniform thin layer chromatography gel layers is described. The apparatus employs rubber cushion runners to compensate for differences in plate thickness and a gel applicator which functions independently of plate edge variability. Consistently uniform layers are prepared by careful establishment of the plate-to-applicator distance. Silica gel layers averaged 87% of the applied thickness with a variability of +/-2% within a single run and +/-8% between independent runs.

Lithium induced alterations in rat ganglionic lipids.

Superior cervical ganglia from normal or lithium fed rats were incubated in vitro with [U-14C]pyruvic acid, in Krebs-Ringer solution with or without lithium ion. Acute lithium incubations were performed on ganglia from normal rats with 25 mEquiv./l of lithium ion, while chronic incubations were performed on ganglia from lithium fed rats with 0.5 mEquiv./l lithium in the bathing solution. Lipids were extracted, separated by thin layer chromatography and specific activities of individual lipids and their fatty acids determined. In control ganglia shinogolipids contained 60-70% of the lipid radioactivity, glycerophospholipids 20-30% and neutral lipids 10-25%. Phosphatidylcholine contained 65% of the glycerophospholipid label and 40% of the lipid phosphorus, while sphingomyelin contained 90% of the sphingolipid label and exhibited the highest specific activity over all. Cholesterol was the major neutral lipid. Niety-five per cent of the glycerophospholipid label and 4% of the sphingomyelin label was localized in the fatty acids. The lipid and fatty acid compositions of all ganglia were similar. However the lipid radioactivity in chronic ganglia was lower than in control, with the sphingolipids most affected. In 80 min stimulated chronic ganglia stearic and oleic acid, radioactivity was depressed with respect to both control fatty acids and to the [14C]palmitate of chronic tissues. In both chronic and acute lithium ganglia stimulated for 80 min, the specific activities of phosphatidylinositol were significantly lower than in control. In contrast to control, the labeling of sphingolipids in resting acute ganglia was higher than in stimulated tissues.