A case of acute exacerbation of chronic pulmonary thromboembolism with essential thrombocythemia during treatment for hemoptysis]

An 89-year-old woman with essential thrombocythemia and chronic respiratory failure was admitted for treatment of hemoptysis. She stopped taking aspirin and was given tranexamic acid. Though her hemoptysis improved, respiratory failure suddenly worsened. As a result of various examinations and laboratory findings, acute exacerbation of chronic pulmonary thromboembolism was diagnosed. Though there was the risk of recurrence of hemoptysis, she started taking aspirin again. Her respiratory failure improved but hemoptysis did not reappear. Thrombosis and hemorrhage are common complications of essential thrombocythemia, however, pulmonary thromboembolism is a rare complication. There is a possibility that the exacerbation of this case was caused by tranexamic acid as well as rest and cessation of aspirin. If a patient with essential thrombocythemia bleeds, we should be careful when using tranexamic acid.     

Left Ventricular Diastolic Dysfunction in End‐Stage Kidney Disease: Pathogenesis,Diagnosis, and Treatment

Diastolic dysfunction is frequently observed in end‐stage kidney disease (ESKD), and ESKD patients have many risk factors for heart failure (HF), including hypertension, diabetes, and coronary artery disease. Diastolic HF, also called HF with preserved ejection fraction, refers to a clinical syndrome in which patients have symptoms and signs of HF, normal or near normal left ventricular (LV) systolic function, and evidence of diastolic dysfunction manifested by abnormal LV filling and elevated filling pressure. Recent reports suggest that HF with preserved ejection fraction is more common in hemodialysis patients than HF with low ejection fraction. Diastolic HF in ESKD patients is a strong predictor of death. In this article, we review the information available in the literature on the pathogenesis, diagnosis, and potential treatment strategies of diastolic dysfunction or diastolic HF based on evidence obtained in the general population that is potentially applicable to ESKD patients.     

Aortic reservoir function after arterial switch operation in elementary school-aged children

BACKGROUND: After the arterial switch procedure, decreased distensibility of the aortic root has been reported, which means impaired aortic reservoir function of the coronary circulation, but there have been no reports regarding the relationship of this issue to myocardial perfusion. Therefore, in the present study the aortic reservoir function and coronary supply-demand balance were examined in patients after undergoing the arterial switch operation (ASO) around the time of entering elementary school. METHODS AND RESULTS: Diastolic runoff (DR), which is the percentage of diastolic blood flow to total cardiac output, was measured as the index of aortic reservoir function. The subendocardial viability ratio was investigated as the index of coronary supply - demand balance. In the patient group, the aortic root was dilated (p<0.0001) and distensibility was impaired (p<0.0001) in comparison with an age-matched control group. However, there was no difference between the 2 groups in DR or subendocardial viability ratio. CONCLUSIONS: Coronary supply - demand balance was preserved in the pediatric ASO patients, despite the aortic root dysfunction. The preserved DR suggests that dilatation of the aorta compensates for aortic reservoir function. Because large artery dysfunction predicts future cardiovascular diseases, careful follow-up is crucial.     

Relation between mixed venous blood oxygen saturation and cardiac pumping function at the acute phase of myocardial infarction

In this study, we monitored changes in the mixed venous blood oxygen saturation (Sv-O2) level of 45 patients with acute myocardial infarction and compared these results to the traditional parameters. The Sv-O2 level was found to correlate well with the clinical course of patients and their hemodynamic conditions. The mean Sv-O2 level of the group having congestive heart failure (53.3 +/- 8.4%) was found to be statistically lower than those without (69.8 +/- 5.6). Furthermore, patients whose Sv-O2 level was lower than 60% were found to be at greater risk for heart failure and a very high mortality rate. Patients were classified into four subsets according to Forrester's hemodynamic classification; their Sv-O2 levels were 70.7 +/- 4.1% (I: 23 cases), 54.7 +/- 6.9% (II: 8 cases), 55.8 +/- 9.4% (III: 10 cases), and 47.0 +/- 8.0 (IV: 4 cases), respectively. A severe relationship between pulmonary capillary wedge pressure and Sv-O2 having a correlation coefficient of r = -0.64 was observed, and a logarithmic curvilinear relation between cardiac index approximately Sv-O2, stroke volume index approximately Sv-O2 and left ventricular stroke work index approximately Sv-O2 was also evident. When the decrease in the Sv-O2 level was more than 5%, it always showed a significant decrease in the cardiac index. This study suggested tht continuous monitoring of the Sv-O2 level revealed simultaneous changes in the hemodynamic state, which lead to the assistance and aid for treating patients with critical conditions of acute myocardial infarction. In such circumstances, it was noted that the Sv-O2 level should be maintained above 60% in order to stabilize the hemodynamic state.     

Crystal structure of aldoxime dehydratase and its catalytic mechanism involved in carbon-nitrogen triple-bond synthesis

Aldoxime dehydratase (OxdA), which is a unique heme protein, catalyzes the dehydration of an aldoxime to a nitrile even in the presence of water in the reaction mixture. Unlike the utilization of H₂O₂ or O₂ as a mediator of catalysis by other heme-containing enzymes (e.g., P450), OxdA is notable for the direct binding of a substrate to the heme iron. Here, we determined the crystal structure of OxdA. We then constructed OxdA mutants in which each of the polar amino acids lying within ∼6 Å of the iron atom of the heme was converted to alanine. Among the purified mutant OxdAs, S219A had completely lost and R178A exhibited a reduction in the activity. Together with this finding, the crystal structural analysis of OxdA and spectroscopic and electrostatic potential analyses of the wild-type and mutant OxdAs suggest that S219 plays a key role in the catalysis, forming a hydrogen bond with the substrate. Based on the spatial arrangement of the OxdA active site and the results of a series of mutagenesis experiments, we propose the detailed catalytic mechanism of general aldoxime dehydratases: (i) S219 stabilizes the hydroxy group of the substrate to increase its basicity; (ii) H320 acts as an acid-base catalyst; and (iii) R178 stabilizes the heme, and would donate a proton to and accept one from H320.     

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10^-2 and 4.42×10^-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.