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The cause of the circadian variation in the incidence of acute myocardial infarction (AMI) has not been identified. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) have opposing effects on thrombi. Hence, the extent of the clot, the size of the infarct and outcome of patients could depend on t-PA and PAI-1 levels. In an effort to elucidate the pathophysiologic basis of circadian variation of AMI, we investigated the presence of a possible corresponding circadian variation in the levels of endogenous t-PA and PAI-1 in patients diagnosed to have AMI and the effects of hypertension, diabetes and site of the infarct on these levels. We estimated the levels of t-PA and PAI-1 in platelet-poor plasma of 42 patients with AMI on admission, using the enzyme-linked immunosorbant assay. Although not statistically significant, patients having an AMI in the morning hours had the highest t-PA:PAI-1 ratio. The normal circadian variation in PAI-1 levels was lost in patients with AMI, probably due to the disease process. Also, the t-PA levels in hypertensive patients were significantly lower than in nonhypertensives. PAI-1 levels were also significantly lower in patients with anteroseptal than in inferior and anterolateral AMI. This relationship between the fibrinolytic potential and the site of infarction needs further study. Furthermore, t-PA levels on admission were significantly lower in survivors and may have a predictive value in determining the outcome. 相似文献
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A 58-year-old male presented with fatigue, tiredness, and pruritus after hot showers and an elevated white blood cell count (20000/mm(3)). A diagnosis of polycythemia vera (PV) was made after investigation revealed a low erythropoietin and elevated leukocyte alkaline phosphatase (LAP) score; he was treated with repeated phlebotomies. Two years later he developed elevated white counts again and investigation revealed Philadelphia chromosome positive (19/20 cells) chronic myelocytic leukemia (CML). The karyotype also revealed trisomy 9 in 1 of 20 cells. He was treated with imatinib mesylate and went into clinical, hematologic, cytogenetic, and molecular remission. Repeat chromosomal analysis revealed absence of Philadelphia chromosome and BCR/ABL translocation but presence of trisomy 9. To our knowledge, this is the first reported case of coexisting PV and CML both associated with separate chromosomal abnormalities. This also raises an interesting therapeutic consideration of using concomitant imatinib mesylate and hydroxyurea. 相似文献
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Carlos R Ferreira Dillon Kavanagh Ralf Oheim Kristin Zimmerman Julian Stürznickel Xiaofeng Li Paul Stabach R Luke Rettig Logan Calderone Colin MacKichan Aaron Wang Hunter A Hutchinson Tracy Nelson Steven M Tommasini Simon von Kroge Imke AK Fiedler Ethan R Lester Gilbert W Moeckel Björn Busse Thorsten Schinke Thomas O Carpenter Michael A Levine Mark C Horowitz Demetrios T Braddock 《Journal of bone and mineral research》2021,36(5):942-955
Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR). 相似文献
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Aneurysm of sinus of Valsalva dissecting into interventricular septum is a rare entity. We report one such case who was incidentally diagnosed by echocardiography to have this abnormality during evaluation of a clinically suspected isolated aortic regurgitation.KEY WORDS: Aneurysm – dissecting – sinus of Valsalva, Echocardiography 相似文献
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