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Background— Little is known about the impact of technological and pharmacological advances on long-term outcome after percutaneous coronary intervention in general clinical practice. Methods and Results— We analyzed in-hospital and long-term outcome of 24 410 percutaneous coronary interventions among 18 575 unique patients who underwent percutaneous coronary intervention at Mayo Clinic over 25 years. The study population was divided into group 1 (n=3708), coronary interventions from 1979 to 1989; group 2 (n=7020), interventions from 1990 to 1996; group 3 (n=10 952), interventions from 1996 to 2003; and group 4 (n=2730), interventions from 2003 to 2004. Despite the fact that patients in groups 3 and 4 were significantly older, sicker, and had greater prevalence of comorbid conditions, heart failure, and previous revascularization than those in groups 1 and 2, procedural success in groups 3 and 4 improved significantly (94%) versus groups 2 (89%) and 1 (78%) ( P <0.001). Significant reduction in in-hospital mortality (groups 4 to 1: 1.8%, 1.7%, 2.6%, 3.0%; P <0.001) and need for emergency bypass surgery (groups 4 to 1: 0.4%, 0.5%, 1.6%, 5%; P <0.001) was noted in groups 3 and 4 compared with groups 1 and 2. Better adherence to currently recommended evidence-based medications for secondary prevention was seen in the recent time periods. After adjustment, significant reduction in follow-up mortality (hazard ratio, 0.81 and 0.74 for groups 3 and 4, respectively); death or myocardial infarction (hazard ratio, 0.80 and 0.75 for groups 3 and 4, respectively); death, myocardial infarction, or revascularization (hazard ratio, 0.76 and 0.58 for groups 3 and 4, respectively) was noted in recent time periods. Conclusions— Despite higher-risk profiles of patients who underwent percutaneous coronary intervention in recent time periods, procedural success as well as in-hospital and long-term outcomes improved significantly over the last 25 years.

ABSTRACTWe studied the association between HLA alleles and rubella-specific gamma interferon (IFN-γ) (Th1) and interleukin-10 (IL-10) (Th2) cytokine responses among 106 healthy children (ages, 14 to 17 years) previously immunized with two doses of rubella vaccine. Antibody titers and cytokine responses to rubella vaccination were not sex or age dependent. Several class I HLA-A (*0201, *2402, *6801) alleles were significantly associated with rubella vaccine-induced IFN-γ secretion. Several class II HLA-DRB1 (*0101) and HLA-DQB1 (*0501) alleles were also suggestive of an association with IFN-γ secretion. Alleles with potential associations with rubella-specific IL-10 production included HLA-A (*0201, *6801), HLA-B (*4901), and HLA-DRB1 (*1302). The class I A*0201 and A*6801 alleles were associated with both IFN-γ and IL-10 secretion. These tentative associations need to be validated in larger studies with subjects of differing ethnicities. These results provide additional evidence that HLA genes may influence Th1- and Th2-specific cytokine response(s) following rubella immunization, which in turn can influence both cellular and humoral immune responses to rubella vaccination.

AbstractPhosphatidylcholine acyltransferase (lecithin:cholesterol acyltransferase or LCAT; EC 2.3.1.43) activity was found to be present in pig ovarian follicular fluid (POFF), in addition to pig serum (PS). The cholesterol esterification rate in both POFF and PS is linear with incubation time up to 2 hr. The mean absolute rate of POFF‐cholesterol esterification was 8.1±0.4 nmoles per ml per hr approximately one‐fourth of that in PS. However, the fractional rate (percent of labeled cholesterol esterified per hr) of POFF‐cholesterol esterification was similar to that observed in PS. There was little variation of absolute rate of cholesterol esterification in the fluid obtained from different sizes of follicles. Fatty acid or triacylglycerol did not participate in the reaction of cholesterol esterification in POFF. No appreciable change in enzymatic activity was found from storing POFF at 4 C for periods of time up to 24 hr or at −70 C up to 2 months, but activity was lost thereafter. On the other hand, PS showed a much longer period of stability (5 days at 4 C and 9 months at −70 C). A discrepancy between the fatty acid composition of cholesteryl esters formed by the LCAT reaction and the fatty acid composition at the C‐2 position of phosphatidylcholine led us to propose a two‐step mechanism for the LCAT reaction. It is concluded that the LCAT of POFF, as well as that of plasma, is specific for individual fatty acids rather than for the fatty acid composition of phosphatidylcholine. The fatty acid concentration of lysophosphatidylcholine decreased during prolonged incubation times (6 to 21 hr) suggesting that the increased lysophosphatidylcholine formed as a product of the LCAT reaction may be reused as substrate for the LCAT reaction or for hydrolysis by lysophosphatidylcholine hydrolase.

Purpose High-grade gliomas (HGGs; WHO grades 3-4) are highly diverse, with survival times ranging from months to years. WHO 2000 grading criteria for high-grade oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and anaplastic oligodendroglioma (AO)] remain subjective, and the existence of grade 4 variants is controversial. Patients and Methods Overall survival (OS) of 1,093 adult patients with a cerebral HGG newly diagnosed between 1990 and 2005 was analyzed by univariate and multivariate models for significance of the following factors: patient age, surgery type, year of diagnosis, endothelial proliferation, necrosis, oligodendroglial histology, treatment center, and chromosome 1p, 19q, 7p (EGFR), and 10q (PTEN) abnormalities by fluorescence in situ hybridization (FISH). Results Necrosis was a statistically significant predictor of poor OS on univariate and multivariate analyses in AOA but not in AO. Median OS for patients with necrotic AOA (22.8 months) was significantly worse than for patients with non-necrotic AOA (86.9 months; P < .0001) but was better than conventional glioblastomas (9.8 months; P < .0001). In addition to patient age, the following were significant independent prognostic factors (P ≤ .001): grade and surgery type for the entire HGG cohort; modified grade for AOA (3 v 4); and modified grade, 1p/19q codeletion status, and oligodendroglial histology for the 586 HGGs analyzed by FISH. Conclusion Stratification of AOA, but not of pure AO, into grades 3 and 4 on the basis of necrosis is prognostically justified and is more powerful than the current approach. Both routine histology and genetic testing provide independent, prognostically useful information.

Intrahepatic islet transplantation is an experimental therapy for type 1 diabetes. In the present studies, we sought to address the following questions: 1) In humans, do intrahepatic transplanted islets reestablish coordinated puslatile insulin secretion? and 2) To what extent is insulin secreted by intrahepatic transplanted islets delivered to the hepatic sinusoids (therefore effectively restoring a portal mode of insulin delivery) versus delivered to the hepatic central vein (therefore effectively providing a systemic form of insulin delivery)? To address the first question, we examined insulin concentration profiles in the overnight fasting state and during a hyperglycemic clamp (∼150 mg/dl) in 10 recipients of islet transplants and 10 control subjects. To address the second question, we measured first-pass hepatic insulin clearance in two recipients of islet autografts after pancreatectomy for pancreatitis versus five control subjects by direct catheterization of the hepatic vein. We report that coordinate pulsatile insulin secretion is reestablished in islet transplant recipients and that glucose-mediated stimulation of insulin secretion is accomplished by amplification of insulin pulse mass. Direct hepatic catheterization studies revealed that intrahepatic islets in humans do deliver insulin directly to the hepatic sinusoid because ∼80% of the insulin is extracted during first pass. In conclusion, intrahepatic islet transplantation effectively restores the liver to pulsatile insulin delivery.