Apolipoprotein E polymorphisms in Japanese patients with polypoidal choroidal vasculopathy and exudative age-related macular degeneration

PURPOSE: To study the genotypes, allelic frequencies, and polymorphisms of apolipoprotein E (Apo E) in unrelated Japanese patients with polypoidal choroidal vasculopathy (PCV) or exudative age-related macular degeneration (AMD) and control subjects without macular degeneration. DESIGN: Cross-sectional study. METHODS: Blood samples from 225 subjects older than 50 years were used. The 225 subjects included 58 patients with PCV, 85 with AMD, and 82 without macular degeneration. Coding exons of the Apo E gene were amplified by polymerase chain reaction, and the DNA sequences were determined by direct sequencing with an automated sequencer. RESULTS: Apo E epsilon3/epsilon3 was the most frequent genotype with a prevalence of 79.3% in PCV patients, 76.5% in AMD patients, and 67.1% in the control subjects. However, the differences in the percentages were not statistically significant among the three groups. The most frequently found allele in the three groups was epsilon3. Patients with PCV and AMD were less likely to have epsilon2 and epsilon4 than the control subjects, but the differences were not statistically significant. Five minor Apo E single nucleotide polymorphisms, including epsilon5 and epsilon7, were found. CONCLUSION: Japanese patients with PCV and AMD were less likely to have epsilon2 and epsilon4 polymorphisms, but the differences from the normals were not statistically significant for the Apo E genotypes and allelic frequencies.     

Modification of alpha1 -adrenoceptors by peroxynitrite as a possible mechanism of systemic hypotension in sepsis

OBJECTIVE: It is well known that nitric oxide synthase is induced by endotoxin or inflammatory cytokines, and consequently large amounts of nitric oxide cause vascular hyporeactivity to vasoconstrictor agents and myocardial dysfunction, hence hypotension. However, there is considerable controversy as to whether these pathologic cardiovascular features are mediated directly by nitric oxide or also through the formation of secondary reaction products such as peroxynitrite (ONOO-1). Our objective was to investigate inhibitory effects of ONOO-1 on alpha1-adrenoceptors. DESIGN: Prospective, controlled, in vitro, laboratory study. SETTING: Laboratory of a health sciences university. SUBJECTS: Chinese hamster ovary cells that expressed the human recombinant alpha1a-, alpha1b-, or alpha1d-adrenoceptors, rat aorta strips. INTERVENTIONS: Binding experiments of [3H]prazosin were done in the Chinese hamster ovary cell membranes pretreated with 100 microM to 3 mM ONOO-1. Displacement experiments with noradrenaline or 3-nitro-l-tyrosine also were conducted. Mobilization of intracellular Ca2+ evoked by 1 nM to 10 microM noradrenaline was monitored in a fluorescence spectrophotometer with dual excitation at 340 nm/380 nm and emission at 500 nm in fura-2/AM-loaded Chinese hamster ovary cells. Contractile force produced by noradrenaline was monitored in rat aorta strips that have alpha1a- and alpha1d-adrenoceptors, pretreated with 1 mM ONOO-1. Either 0.3 N NaOH or the decomposed ONOO-1 was used as the control. MEASUREMENTS AND MAIN RESULTS: The specific binding of [3H]prazosin to alpha1a- and alpha1d-adrenoceptor was inhibited by ONOO-1 in a concentration-dependent manner. We found that 3 mM ONOO-1 decreased maximum binding sites by 40% to 50% in alpha1a- and alpha1d-adrenoceptors. Binding affinities for prazosin and noradrenaline were not affected by 1 mM ONOO-1 in all subtypes. We found that 3-nitro-l-tyrosine did not affect the prazosin binding to three adrenoceptor subtypes. Noradrenaline increased intracellular Ca2+ concentration ([Ca2+]i) concentration-dependently, which was inhibited by ONOO-1 in alpha1a- and alpha1d-adrenoceptors. ONOO-1 had no effect on alpha1b-adrenoceptor. Contractile force produced by noradrenaline decreased significantly in aorta strips pretreated with ONOO-1. CONCLUSION: ONOO-1 reduces the binding capacity of alpha1a- and alpha1d- but not alpha1b-adrenoceptors without changing the affinities. Treatment with ONOO-1 attenuates noradrenaline-stimulated increase in [Ca2+]i in alpha1a- and alpha1d-adrenoceptors but not in alpha1b-adrenoceptor. ONOO-1 also weakens noradrenaline-induced contractions in rat aorta that has alpha1a- and alpha1d-adrenoceptors. Cardiovascular hyporeactivity to catecholamines in septic shock may be caused in part by the inactivation of alpha-adrenoceptors by ONOO-1.     

Clinical study of biocompatibility between open and closed heparin-coated cardiopulmonary bypass circuits

The objective of this study was to investigate the difference between the closed circuit system and the open circuit system in clinical heparin-coated cardiopulmonary bypass (CPB) circuits with a centrifugal pump. We evaluated the coagulation, fibrinolysis, and inflammatory response in valvular heart surgery. Nineteen patients were assigned at random to a group for the closed circuit system or the open circuit system. This is the first report on the effect of a closed circuit in valvular surgery. We measured the platelet count, white blood cell count, plasma fibrinogen concentration, thrombin–antithrombin III complex, plasmin-2 plasmin inhibitor complex, D-dimer, interleukin-6, polymorphic neutrophil-elastase, and the plasma free hemoglobin. Blood samples were collected before the start of perfusion, 15 and 60min after the start of perfusion, 60min after the administration of protamine, and 1 day after the operation. During the perfusion, coagulation, fibrinolysis, and inflammatory responses were activated; however, no significant differences between the two groups were noted. In this clinical investigation with suction and the cell saving system, the closed circuit was not found to be superior to the open circuit with regard to biocompatibility.     

Prognostic value of nonlinear heart rate dynamics in hemodialysis patients with coronary artery disease

BACKGROUND: Although altered nonlinear heart rate dynamics predicts death in patients with coronary artery disease (CAD), its prognostic value in chronic hemodialysis patients with CAD is unknown. METHODS: We analyzed 24-hour electrocardiogram for nonlinear heart rate dynamics and heart rate variability in a retrospective cohort of 81 chronic hemodialysis patients with CAD. RESULTS: During a follow-up period of 31 +/- 20 months, 19 cardiac and 8 noncardiac deaths were observed. Cox hazards model, including diabetes, left ventricular ejection fraction, and the number of diseased coronary arteries, revealed that abnormal alpha2 (defined as both increase and decrease in alpha2 because of its J curve relationship with cardiac mortality), decreased approximate entropy and decreased heart rate variability (triangular index and ultra-low frequency power) were significant and independent predictors of cardiac death. No significant and independent predictive power for noncardiac death was observed in either the heart rate dynamics or the heart rate variability measures. The predictive power of alpha2 and approximate entropy was independent of that of triangular index and ultra-low frequency power. Combinations of two categories of measures improved the predictive accuracy; overall accuracy of approximate entropy + ultra-low frequency power for cardiac death was 87%. CONCLUSION: Altered nonlinear heart rate dynamics are independent predictors of cardiac death in chronic hemodialysis patients with CAD and their combinations with decreased heart rate variability provide clinically useful markers for risk stratification.     

De novo germinoma in the brain in association with Klinefelter's syndrome: case report and review of the literature

BACKGROUND: There are no previous reports about de novo germ cell tumors without any past history of germ cell tumor. We describe a case of de novo cerebral germinoma in association with Klinefelter's syndrome. CASE DESCRIPTION: A boy had undergone growth hormone therapy for dwarfism because of hypopituitarism from 10 to 17 years old. The result of karyotyping at the age of 13 was 47,XXY. Magnetic resonance images (MRI) of the brain at the age of 17 years showed no lesions. Two years later, at the age of 19, the patient noticed onset of mild right hemiparesis. MR imaging revealed the existence of a brain tumor in the left temporal lobe and hypothalamus. The patient underwent an operation and the histologic diagnosis of the lesion was germinoma. After postoperative chemotherapy and radiation therapy, the lesion disappeared and the patient was discharged uneventfully. CONCLUSIONS: To the best of the authors' knowledge, this is the first reported case of a germ cell tumor to be de novo without any past history of other germ cell tumor and the seventh case in which it occurred in association with Klinefelter's syndrome.     

Angiography of Hepatic Vascular Malformations Associated with Hereditary Hemorrhagic Telangiectasia

Purpose: To describe the angiographic features of hepatic involvement in hereditary hemorrhagic telangiectasia (HHT), particularly the presence of portovenous shunts. Methods: We reviewed the angiographic findings of seven patients with HHT. The patients comprised three women and four men with a mean age of 51 years. Results: Intrahepatic telangiectasias were found in all seven patients and shunts between three vascular channels were found in six of seven patients. In the four patients who had portovenous shunts combined with arterioportal shunts, the portovenous shunts were large. Three patients had no portovenous shunts. Two of these patients had arteriovenous shunts, and one had no shunt. The mean age (69 years) of the patients with portovenous shunts was older than those without portovenous shunts (26 years). Conclusions: Hepatic vascular lesions in HHT are varied, ranging from telangiectasias to large shunts between three vascular channels. In an advanced stage of involvement, large portovenous shunts are present.     

Henoch-Schönlein purpura nephritis in a patient infected with the human immunodeficiency virus

There are various forms of renal lesions in patients with human immunodeficiency virus(HIV), however reported cases of immune-complex glomerulonephritis are scarce. Here we describe an HIV-positive patient with Henoch-Sch?nlein purpura nephritis(HSPN), which presented as nephrotic syndrome. In addition to therapy combined with glucocorticosteroid and inhibition of the renin-angiotesin system(RAS), plasmapheresis and antiretroviral therapy produced a favorable outcome. A 26-year-old HIV positive man was admitted for purpura on both lower limbs. Despite glucocorticosteroid treatment, purpura recurred and urinary protein increased to 5-10 g daily. HSPN was diagnosed based on the skin and renal biopsies. During 2 months of treatment with combined glucocorticosteroid and RAS inhibition, nephrotic syndrome persisted. He received double filtration plasmapheresis(DFPP). Soon after, urine protein decreased to 2-3 g daily and macrohematuria decreased. The second renal biopsy showed a decrease in IgA deposition and improvement of acute inflammatory changes. In addition, highly active antiretroviral therapy was started to reduce the high viral load. After 3 weeks, HIV-1-RNA rapidly decreased and urine protein decreased to 1 g daily. After a year, urinary protein was negative, but mild microhematuria persisted. We speculate that the refractory nephrotic syndrome in this patient might be associated with the abnormal immunological condition due to HIV infection.