Long-term Efficacy of Pegylated Recombinant Human Megakaryocyte Growth and Development Factor in Therapy of Aplastic Anemia

We describe a patient with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who developed an extramedullary blast crisis in the central nervous system (CNS) and then a subcutaneous tumor of the neck during treatment with imatinib mesylate. Administered 400 mg of imatinib mesylate after the diagnosis of chronic-phase CML, the patient achieved a complete cytogenetic remission 4 months later. However, he developed a mixed myeloid/B-cell blast crisis with additional karyotype abnormalities only in the CNS during a complete cytogenetic remission in the bone marrow. Several doses of intrathecal chemotherapy and whole-brain irradiation were effective in treating the blast crisis in the CNS. After 7 months of complete cytogenetic remission, the patient experienced a subcutaneous tumor in the right neck. A biopsy of the tumor revealed a mixed myeloid/T-cell blast crisis. The cytogenetic analysis showed that the blast crisis clone in the neck tumor was different from that of the CNS. An increased dose of imatinib mesylate was ineffective in treating the neck tumor. Irradiation to the right neck was therefore undertaken. This case suggests that the development of a clone resistant to imatinib mesylate is not always detected in the bone marrow and that multiple Ph-positive clones have the potential to become transformed into a blast crisis.     

Evaluation of whole left ventricular systolic performance and local myocardial systolic function in patients with prior myocardial infarction using global long-axis myocardial strain

Left ventricular (LV) global strain along its long axis during systole, which is obtained by dividing mitral annular excursion by the distance from the mitral annulus to the LV apex at end-diastole, can be used to assess whole LV systolic performance. The evaluation of LV wall function using this parameter suggests that previous myocardial infarction (MI) causes long-axis myocardial function in remote normal LV walls, as well as in walls with MI, to deteriorate.     

Serum uric acid is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus

Hyperuricemia has been reported to be associated with increased risk of renal insufficiency as well as cardiovascular events. The aim of this study was to evaluate the relationships between serum uric acid concentration and degree of urinary albumin excretion as well as markers of subclinical atherosclerosis in men with type 2 diabetes mellitus. Serum uric acid concentrations were measured in 343 men with type 2 diabetes mellitus. We then evaluated relationships of serum uric acid concentrations to degree of urinary albumin excretion as well as to major cardiovascular risk factors, including age, blood pressure, serum lipid concentration, and glycemic control (hemoglobin A1c). The relationships between serum uric acid concentration and pulse wave velocity or ankle-brachial index (n=236) and between serum uric acid concentration and carotid intima-media thickness or plaque score (n=125) were investigated additionally in a subgroup of patients. Serum uric acid concentration correlated positively with logarithm of urinary albumin excretion (r=0.302, P<.0001). Positive correlation was found between serum uric acid concentration and intima-media thickness (r=0.233, P=.0087), whereas inverse correlation was found between serum uric acid concentration and ankle-brachial index (r=-0.150, P=.0207). Multiple regression analysis demonstrated that serum uric acid concentration (beta=.281, P<.0001), duration of diabetes (beta=.253, P<.0001), hemoglobin A1c (beta=.166, P=.0034), serum triglyceride concentration (beta=.125, P=.0472), and systolic blood pressure (beta=.275, P=.0013) were independent determinants of logarithm of urinary albumin excretion. In conclusion, serum uric acid concentration is associated with microalbuminuria and subclinical atherosclerosis in men with type 2 diabetes mellitus.     

Assessment of a Difference in ALDH2 Heterozygotes and Alcoholic Liver Injury

We have speculated that the degree of liver dysfunction in alcoholic liver disease with ALDH2*1/2*2 may be less pronounced than that with ALDH2*1/2*1 . In the present study, outpatients with alcoholic liver injury were examined for ALDH2 genotype and biochemical data. The number of patients was 29 cases of nonspecific changes, 16 cases of fatty liver, 5 cases of liver fibrosis, and 44 cases of liver cirrhosis. Biochemical data were evaluated with ALDH2 heterozygotes data obtained by PCR-SSCP. The ALDH2*1/2*1 and ALDH2*1/2*2 genotypes accounted for 90% and 10%, respectively. As for ALDH2*1/2*2 , there were three patients with nonspecific changes, three with fatty liver, one with liver fibrosis, and two with liver cirrhosis. In alcoholic liver disease patients, when the ALDH2*1/2*2 genotype was compared with the ALDH2*1/2*1 genotype with biochemical data, the γ-GTP value in patients with ALDH2*1/2*2 was significantly higher than with ALDH2*1/2*1 ( p < 0.005). When the frequency of ALDH2 genotype was determined in patients with alcoholic liver injury, ALDH2 heterozygotes accounted for 15% for the non-cirrhosis group, and 5% for the cirrhotic group. When a relationship between the amount of ethanol intake and biochemical data were determined in patients with alcoholic liver injury who have ALDH2 heterozygotes, the glutamic oxaloacetic transaminase (GOT) and γ-GTP values were significantly higher at an ethanol intake amount of ethanol more than 100 g per day than intake less than 100 g per day ( p < 0.05). The alcoholic patients with ALDH2*1/2*2 drink a slight amount of ethanol, the liver injury is found to be stronger than those with ALDH2*1/2*1 when they drink more than 100 g ethanol per day.     

Diagnosis of cardiac amyloidosis based on the myocardial velocity profile in the hypertrophied left ventricular wall

The myocardial velocity profile (MVP), derived from color-coded tissue Doppler imaging (TDI), can identify transmural heterogeneity based on the physiology and pathology of the myocardium. This study sought to clarify whether the MVP can differentiate cardiac amyloidosis from other causes of left ventricular hypertrophy. We recorded the MVP and determined its myocardial velocity gradient (MVG) in the ventricular septum and left ventricular posterior wall using color-coded TDI in 10 patients with cardiac amyloidosis, in 25 patients with hypertensive hypertrophied left ventricular wall, in 25 patients with asymmetric septal hypertrophy of hypertrophic cardiomyopathy, and in 20 clinically normal controls. End-diastolic ventricular septal thickness was similar among the cardiac amyloidosis, hypertension, and hypertrophic cardiomyopathy groups. Percent systolic thickening of the ventricular septum and left ventricular posterior wall calculated from M-mode left ventricular echocardiograms was lower in the cardiac amyloidosis group than in the hypertension, hypertrophic cardiomyopathy, or control group. Peak MVGs during systole and early diastole were lowest in the cardiac amyloidosis group, followed, in order, by the control, hypertension, and hypertrophic cardiomyopathy groups. The systolic and early diastolic MVPs in the ventricular septum and left ventricular posterior wall showed a characteristic serrated pattern in all patients with cardiac amyloidosis, but not in any other patient groups. In conclusion, MVPs in the ventricular septum and left ventricular posterior wall show a distinctive serrated pattern that may be related to amyloid deposition in the myocardium. Myocardial tissue characterization using color-coded TDI provides diagnostic information in patients with cardiac amyloidosis.     

Hyaluronic acid stimulates tumor-cell proliferation at wound sites

BACKGROUND: For EMR, the submucosal injection of sodium hyaluronate has become popular, because this substance creates a more prominent and longer-lasting mucosal protrusion than normal saline solution. However, the effects of sodium hyaluronate on tumor growth at wound sites remain unclear. METHODS: For these experiments, a murine model with artificial wounds was used. Forty mice were randomly divided into two groups according to the substance to be injected into a wound: a sodium hyaluronate group and a control group. Tumors were created by inoculation of transplantable adenocarcinoma cell line colon 26. Two weeks later, the size, weight, proliferating cell nuclear antigen-labeling index, and CD44 expression of the subcutaneous tumors were compared between the two groups of mice. RESULTS: There were significantly greater increases in the growth and the weight of subcutaneous tumors in the sodium hyaluronate group compared with the control group. The PCNA-labeling index of cancer cells also was higher in the sodium hyaluronate group. Immunohistochemistry and Western blot analysis demonstrated that the CD44 protein expression of cancer cells was higher in the sodium hyaluronate group vs. the control group. CONCLUSIONS: In this study, sodium hyaluronate enhanced both tumor growth and CD44 expression of cancer cells at wound sites, suggesting that the use of sodium hyaluronate for EMR might stimulate the growth of residual tumor cells.