Quantitative expression of erythropoietin receptor (EPO-R) on acute leukaemia cells: relationships between the amount of EPO-R and CD phenotypes, in vitro proliferative response, the amount of other cytokine receptors and clinical prognosis. Japan Adult Leukaemia Study Group

Expression of erythropoietin (EPO) receptor (EPO-R) was analysed in leukaemia cells from 150 patients with acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL). EPO-R was expressed in 81 (60%) out of 136 AML, and in vitro treatment with EPO led to proliferation of leukaemia cells in 13 (16%) out of 81 AML examined. EPO-R expression and in vitro response to EPO were observed in all subtypes of AML according to the French-American-British (FAB) classification. All eight patients with FAB-M6 expressed EPO-R, and one out of four showed an in vitro response to EPO. Although there was no significant correlation (r = 0.2522) between the amount of EPO-R and the in vitro response to EPO, all of the AML patients who showed in vitro response expressed EPO-R. Stem cell factor significantly enhanced both EPO-R expression and in vitro response to EPO. Interleukin-3 tended to increase in vitro response to EPO. CD phenotypes, the amount of granulocyte colony-stimulating factor (G-CSF) receptors and the amount of TPO receptors had no significant relationship with the amount of EPO-R. Patients with both EPO-R expression and in vitro response to EPO had shorter duration of complete remission than those without EPO-R (P = 0.0053). EPO-R was expressed in four (29%) out of 14 ALL, and none out of five ALL showed in vitro response to EPO.     

Coronary revascularization in Japan. Part 1: survey of facilities during 1997.

Coronary artery disease is one of the major causes of morbidity and mortality in industrialized countries, including Japan. Increasing numbers of patients have been treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), but there is little information in Japan concerning the use of revascularization therapy and the facilities. The Japanese Coronary Intervention Study (JCIS) Group conducted a nationwide survey on coronary revascularization procedures and facilities during 1997. A questionnaire was mailed to the presidents or designated delegates of 8,253 laboratories in 7,986 hospitals that had departments of internal medicine and/or cardiovascular medicine and to 578 facilities in 558 hospitals identified by the PCI survey as performing CABG and/or registered in the annual survey carried out by the Japanese Association for Thoracic Surgery. A total of 109,788 PCIs were performed at 1,023 laboratories, and 17,667 CABGs at 477 facilities. PCI and CABG numbers per 10(6) population were 870 and 140, respectively. The ratio of PCI to CABG was 6.2. The numbers of PCI laboratories and CABG facilities per 10(6) population were 8.1 and 3.8, respectively. The majority of PCI laboratories and CABG facilities had a small annual volume: 44% of PCI laboratories and 77% of CABG facilities had annual volumes of 50 or less. Only half of the PCI laboratories had surgical backup on-site. Despite the small volume for each facility, coronary revascularization, especially PCI, is highly utilized in Japan.     

Coronary revascularization in Japan. Part 2: comparison of facilities between 1997 and 1999.

A nation-wide survey on the procedures and facilities of coronary revascularization, percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) conducted by the Japanese Coronary Intervention Study (JCIS) group during 1997 revealed that PCI is more often used than CABG and is mainly carried out in low-volume facilities without surgical backup. The present study aimed to investigate the temporal changes in the usage of revascularization therapies and facilities from 1997 to 1999. A questionnaire was mailed in 1998 to the delegates of 1,086 PCI and 582 CABG facilities identified by the previous survey, and 89% of PCIs surveyed and 94% of CABGs surveyed reported back. The number of PCI procedures had increased by 19% from 97,831 to 116,479 and that of CABG procedures also increased by 21% from 16,374 to 19,846. The ratio of PCI to CABG was 5.9 in 1999, showing no significant change from 6.0 in 1997. In parallel, the number of PCI and CABG facilities increased from 888 to 941 and from 442 to 453, respectively. The use of coronary stents and other interventional devices increased during these 2 years. Coronary stents were used regardless of the annual procedural volume of the facilities, whereas other interventional devices, directional and rotational coronary atherectomy, were used mainly in the high-volume laboratories (p<0.01). Beating-heart, off-pump CABG had increased from 2% to 11% of total cases. Continued monitoring of trends in PCI and CABG facilities and procedures will be needed for nation-wide assessment of the use of new technology.     

Relationship Between CT Volumetry and Functional Liver Volume Using Technetium-99m Galactosyl Serum Albumin Scintigraphy in Patients Undergoing Preoperative Portal Vein Embolization Before Major Hepatectomy: A Preliminary Study

To clarify the relationship between morphological measurements of hepatic volume by computed tomography (CT-vol) and functional volume (RI-vol) by technetium-99m galactosyl human serum albumin (^99mTc-GSA) scintigraphy, and its clinical significance, we examined 16 patients with a background liver status of either normal liver function (n = 4), chronic hepatitis or cirrhosis (n = 7), or obstructive jaundice (n = 5). In five patients who underwent preoperative portal vein embolization (PVE), volumetric measurement was performed 2 weeks after PVE. The mean values of CT-vol and RI-vol of the right lobe were 692± 147 cm³ (66.1 ± 10.7%) and 668 ± 159 cm³ (67.8 ± 13.2%), respectively, and those of the left lobe were 329 ± 138 cm³ (33.9 ± 10.6%) and 328± 170 cm³ (32.2 ± 13.2%), respectively. There were no significant differences in the volume measurements between the two volumetric techniques. Correlations between CT-vol and RI-vol in the right and left lobes were positive and significant (r = 0.912 and 0.903, respectively; both P′s < 0.001). The mean values of post-PVE CT-vol and RI-vol of the right lobe in five patients were significantly different (628 ± 149 and 456± 211 cm³, respectively; P = 0.033). However, the mean values of post-PVE CT-vol and RI-vol of the left lobe were not different (496 ± 124 and 483± 129 cm³, respectively). We propose that volumetric measurement by ^99mTc-GSA scintigraphy is useful for detecting changes in functional volume of individual lobes of the liver and is a more dynamic method compared with detection of morphological changes by CT scan. No financial support was received from any source for this study.     

Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1)

Methylation of cytosine in DNA plays a crucial role in development through inheritable gene silencing. The DNA methyltransferase Dnmt1 is responsible for the propagation of methylation patterns to the next generation via its preferential methylation of hemimethylated CpG sites in the genome; however, how Dnmt1 maintains methylation patterns is not fully understood. Here we report the crystal structure of the large fragment (291-1620) of mouse Dnmt1 and its complexes with cofactor S-adenosyl-L-methionine and its product S-adenosyl-L-homocystein. Notably, in the absence of DNA, the N-terminal domain responsible for targeting Dnmt1 to replication foci is inserted into the DNA-binding pocket, indicating that this domain must be removed for methylation to occur. Upon binding of S-adenosyl-L-methionine, the catalytic cysteine residue undergoes a conformation transition to a catalytically competent position. For the recognition of hemimethylated DNA, Dnmt1 is expected to utilize a target recognition domain that overhangs the putative DNA-binding pocket. Taking into considerations the recent report of a shorter fragment structure of Dnmt1 that the CXXC motif positions itself in the catalytic pocket and prevents aberrant de novo methylation, we propose that maintenance methylation is a multistep process accompanied by structural changes.     

A pancreatobiliary-type carcinoma in situ at the periphery of a mural nodule developed from a gastric adenoma in an intraductal papillary mucinous neoplasm

We report a rare case of an intraductal papillary mucinous neoplasm (IPMN) with a pancreatobiliary-type carcinoma in situ (CIS) that originated around a mural nodule formed in a gastric-type adenoma. A 64-year-old man was admitted to our hospital in December 2001 for dilation of the main pancreatic duct, detected on abdominal ultrasonography. Branch-duct-type IPMN (diameter 25 mm) was diagnosed, and because mural nodules were absent, the patient was annually followed up for 5 years. In 2006, computed tomography scans revealed thickening of the tumor wall and the development of a mural nodule (diameter approximately 6 mm); pancreatoduodenectomy with regional lymph-node dissection was performed. Histopathologic examination showed an intraductal papillary mucinous carcinoma arising from an adenoma. Hematoxylin and eosin (H&E) staining revealed that most of the tumor components, including the mural nodule, had adenomatous changes, indicating the tumor to be of the gastric type; however, immunohistochemistry showed positive MUC2 expression. Histologically, the tissues around the nodule, including those showing a cribriform pattern, were diagnosed as CIS. These tissues were classified as the pancreatobiliary-type on the basis of the results of both H&E staining and immunohistochemistry. The patient remained disease-free for 3 years after surgery.     

Reducing the incidence of post-hepatectomy hepatic complications by preoperatively applying parameters predictive of liver function

Background/purpose

To prevent or reduce hepatic complications after hepatectomy, it is important to employ preoperative predictive parameters and to determine the indications for hepatectomy. In the present study, we evaluated risk parameters in patients who underwent hepatectomy between 1994 and 2003, and selected three parameters to modify the surgical indications. Using these indications before surgery in patients who underwent hepatectomy between 2004 and 2008, we compared the prevalences of postoperative complications in the the two groups of patients.

Methods

We examined 250 consecutive patients who underwent hepatectomy for liver disease [149 in 1994–2003 (termed the early period) and 101 in 2004 to 2008 (termed the later period)].

Results

In the early period, uncontrolled ascites was observed in 55 patients and hepatic failure was observed in 15 of the 149 patients. Multivariate analysis identified volume of the resected liver (≥50%), intraoperative blood loss (≥1500 ml), prothrombin activity (<70%), hyaluronic acid level (≥200 ng/ml), and LHL15 (hepatic uptake ratio of technetium-99m galactosyl human serum albumin (^99mTc-GSA) (<0.85) as risk factors; the latter three parameters were evaluated as predictors of outcome. From 2004, we used these three parameters, in addition to the indocyanine green retention rate at 15 min (ICGR15), as criteria for indications for hepatectomy. Despite the lower prevalence of normal liver in the later period, comparisons showed decreases in the rates of uncontrolled ascites (23 vs. 37%, P = 0.03), hepatic failure (4 vs. 10%, P = 0.12), and hepatic complications (25 vs. 44%, P = 0.003) in patients in the later period compared with these rates in the previous period.

Conclusions

The use of prothrombin activity, and levels of hyaluronic acid and LHL15, as parameters of functional liver reserve in the selection of candidates for surgery reduced the incidence of hepatic complications after hepatectomy.     

Mortality and readmission of hospitalized patients with congestive heart failure and preserved versus depressed systolic function

Patients with congestive heart failure (CHF) and preserved systolic function are very common. Despite the high prevalence of this syndrome, very little information is known regarding its mortality and morbidity (e.g., readmission), or the efficacy of drugs. The purpose of this study was to compare the clinical characteristics and prognosis among consecutively hospitalized patients with CHF and preserved versus depressed left ventricular systolic function. Patients with severe aortic or mitral valve disease were excluded from the study. Patients were categorized based on the values of ejection fraction (EF) as having "preserved" (EF>50%), "intermediate" (EF 40% to 50%), or "depressed" (EF<40%) systolic function. Clinical characteristics as well as mortality and hospital readmission rates during 2.4 years of follow-up were recorded for each patient. Sixty-one patients (35%) had preserved systolic function, 73 (43%) had depressed function, and 38 (22%) had intermediate function. Patients with preserved systolic function were more often women and had a higher prevalence of left ventricular hypertrophy (all p <0.05). At follow-up, cumulative survival probabilities were similar between patients with preserved systolic function and those with systolic dysfunction (p = 0.84). Readmission rates were also comparable between preserved and depressed systolic function (36% vs 48%; p = NS). The prognosis of CHF patients with preserved systolic function was similar to those with systolic dysfunction. In light of these findings, effective therapeutic strategy for this subset of patients is needed.     

Diagnostic usefulness of postexercise systolic blood pressure response for detection of coronary artery disease in patients with echocardiographic left ventricular hypertrophy

BACKGROUND: Although exercise-induced electrocardiographic ST segment changes are used to detect coronary artery disease (CAD), their diagnostic value is markedly decreased in patients with left ventricular (LV) hypertrophy. There have been no reports concerning postexercise systolic blood pressure (SBP) response in patients with ultrasound echocardiographic (UCG) LV hypertrophy and CAD. METHODS: Sixty-six patients with both UCG-LV hypertrophy (LV mass index 134 g/m2 or greater for men or 110 g/m2 or greater for women) and positive ST depression of at least 0.1 mV during treadmill exercise testing were studied. Coronary cineangiograms showed normal coronary arteries in 19 patients (group 1) and significant CAD in 47 patients (group 2). The SBP ratio was calculated by dividing the SBP 3 min after exercise (3 min SBP) by the SBP at peak exercise (peak SBP). RESULTS: There were no significant differences between the two groups in LV mass index, SBP at rest, exercise duration, ST depression (at rest and exercise-induced) or 3 min SBP. However, the SBP ratio was significantly higher in group 2 compared with group 1 (0.87+/-0.11 versus 1.01+/-0.18; P=0.004). Analysis of relative cumulative frequency distributions revealed an SBP ratio of 0.92 as the cutoff point for distinguishing a UCG-LV hypertrophy patient with CAD from one without CAD. The sensitivity, specificity and accuracy with an SBP ratio of 0.92 and an ST segment depression of at least 0.1 mV on treadmill exercise testing for detecting CAD in patients with UCG-LV hypertrophy were 77%, 74% and 76%, respectively. CONCLUSION: These findings suggest that the ratio of early post-exercise SBP to peak exercise SBP may be diagnostically useful in detecting CAD in patients with positive ST depression during an exercise test and UCG-LV hypertrophy.