Incidence and clinical characteristics of chronic pulmonary thromboembolism in Japan compared with acute pulmonary thromboembolism: results of a multicenter registry of the Japanese Society of Pulmonary Embolism Research.

The incidence of acute pulmonary thromboembolism (APTE) in Japan is quoted as being extremely low compared with the United States, and the incidence and clinical characteristics of chronic pulmonary thromboembolism (CPTE) in Japan is unknown, so this study investigated these aspects of CPTE in 309 patients with APTE and 68 patients with CPTE. The ratio of the incidence of CPTE to APTE was 0.22 and there was no significant difference in age or sex between the APTE and CPTE patients. All of the predisposing factors for pulmonary thromboembolism, except for thrombophilia, were more frequently seen in the patients with APTE. There are some differences in the incidence and clinical characteristics of CPTE compared with APTE between Japanese and American patients in Japan, suggesting that the pathogenesis of CPTE in Japan may differ from that in the USA.     

Chronic Kidney Disease Japan Cohort (CKD-JAC) study: design and methods

The prevalence and incidence of end-stage renal disease (ESRD) in Japan are the highest and the third highest, respectively, in the world, while the incidence of cardiac death in Japan is the lowest among developed countries. A recent study showed that the prevalence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (GFR) of less than 60 mL/min/1.73 m(2), is extremely high in Japan, about 20% of the adult population. However, the risk of ESRD and cardiovascular disease (CVD) in the CKD population has not been determined nationwide. For this observational study, we will establish a Chronic Kidney Disease Japan Cohort (CKD-JAC) by enrolling 3,000 patients with CKD in 17 clinical centers around Japan, which will be used to determine the incidence of ESRD and CVD in Japanese CKD patients. Risk factors associated with the development of CVD will also be examined. Comorbidity of diabetes in CKD patients will be analyzed to determine whether it is a risk for rapid progression of CKD and high incidence of CVD. In addition, we will study whether the burden of CKD decreases the QOL of patients, and increases hospitalization or health resource utilization. Insights from the CKD-JAC study will provide a basis for future interventional trials focused on reducing the burden of ESRD and CVD in patients with CKD in Japan.     

Experience with 1904 laparoscopic cholecystectomies at a private hospital

The purpose of this paper is to describe our recent experience in performing laparoscopic cholecystectomies of which we performed 1904, from January 1991 to May 1997, at our private hospital, mainly to treat cholecystolithiasis. The patients included 1563 with gallbladder stones (82.0%), 82 with cholecystocholedocholithiasis (4.3%), 104 with adenomyomatosis (5.5%), 132 with polyps (6.9%), and 23 with gallbladder cancer (1.3%). A difficult pericholecystic dissection led to conversion to open surgery in 61 patients. The average operation time was 63 min. Bile duct injury or cystic artery bleeding occurred in 3 patients with acute cholecystitis, and small intestine injury occurred in 1 patient, while bile leakage or a right subphrenic abscess occurred in 6 patients postoperatively. Although this series included 69 patients with previous upper abdominal surgery, 14 with liver cirrhosis, 267 with a nonvisualized gallbladder, and 148 with acute cholecystitis, the overall conversion rate was only 3.2% and morbidity only 0.5%. Although almost all patients with cholelithiasis are now considered potential candidates for a laparoscopic cholecystectomy, difficulties during cholecystectomy have been encountered in patients with acute cholecystitis. Surgeons should thus be fully prepared to convert to open surgery whenever difficulties are encountered, in order to avoid complication.     

Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor: possible role of AT1 receptor dimerization

AIMS: We recently demonstrated that aldosterone induces a non-genomic vasoconstrictor effect on rat coronary arterioles and that this effect was blocked by angiotensin II type 1 receptor (AT1) blockers. Intracellular transglutaminase enhances AT1 signalling by cross-linking AT1 homodimers. The purpose of this study was to confirm the AT1-dependency of the vasoconstrictor effect of aldosterone using AT1a knockout (AT1aKO) mice and to investigate the role of intracellular transglutaminase and AT1 dimerization in this effect. METHODS AND RESULTS: The mesenteric arterioles (60-160 microm) were isolated from C57BL/6J (wild-type, WT) and AT1aKO mice, and the internal diameter was measured by video microscopy. Aldosterone (10(-13) to 10(-6) M), but not hydrocortisone, produced a dose-dependent vasoconstriction in WT mice; the maximal diameter change was -8.6 +/- 0.3% from the baseline (P < 0.001). This vasoconstrictor effect was unaffected by the mineralocorticoid receptor antagonist spironolactone or eplerenone, the AT2 antagonist PD123319, the glucocorticoid receptor antagonist RU486, or endothelium denudation. Aldosterone's vasoconstrictor effect was negligible in AT1aKO mice. The AT1 blockers valsartan or candesartan suppressed aldosterone-induced vasoconstriction in WT mice. The transglutaminase inhibitors cystamine and monodansyl cadaverine also suppressed the vasoconstrictor effect of aldosterone, without affecting the vasoconstrictor effect of angiotensin II in WT mice. AT1 dimer protein levels were increased in WT mesenteric arterioles treated with 10(-7) M aldosterone, and the transglutaminase inhibitor and AT1 blocker blocked this aldosterone-induced formation of AT1 dimer. Treatment with 10(-7) M aldosterone for 10 min increased the transglutaminase activity by 2.5 +/- 0.2-fold in cultured vascular smooth muscle cells and by 1.2 +/- 0.1-fold in the mesenteric arterioles. These increases were abolished by transglutaminase inhibitors. CONCLUSION: Aldosterone produces a non-genomic, endothelium-independent vasoconstrictor effect by enhancing intracellular transglutaminase activity and presumably inducing AT1 dimer formation in mesenteric arterioles.     

An autopsy case of granulocyte-colony-stimulating-factor-producing extrahepatic bile duct carcinoma

A 79-year-old man was referred to this department due to the presence of extrahepatic bile duct carcinoma with a tumor at the left chest wall. The lesion was suspected to be a metastasis of bile duct carcinoma to the left wall, however, computed tomography （CT） revealed no regional lymph node or liver metastases. In addition, cytological and pathological examinations did not show malignancy. At the time of admission, the white blood cell count was 21 460 cells/μL （neutrophils, 18 240 cells/μL） and this elevated to 106 040 before death. In addition, serum granulocyte colony-stimulating factor （G-CSF） was elevated. At 28 d after admission, the patient died. An autopsy showed a poorly differentiated adenocarcinoma with sarcomatous change, which had slightly invaded into the pancreas around the bile duct, and was found in the distal bile duct with multiple metastases to the chest wall, lung, kidney, adrenal body, liver, mesentery, vertebra and mediastinal and para-aortic lymph nodes, without locoregional lymph node and liver metastasis. The cancer cells showed positive immunohistochemical staining for anti-G-CSF antibody. This is believed to be the first report of an extrahepatic bile duct carcinoma that produces G-CSF. Since G-CSF-producing carcinoma and sarcomatous change of the biliary tract leads to poor prognosis, early diagnosis and treatment are needed. When infection is ruled out, the G-CSF in serum should be examined. In addition, examinations such as bonescintigraphy and chest CT should also be considered for distant metastasis.     

Regular exercise,hormone replacement therapy and the age-related decline in carotid arterial compliance in healthy women

OBJECTIVE: Carotid arterial compliance is reduced with age in sedentary estrogen-deficient women, contributing to the development of cardiovascular disorders. We determined the effects of regular aerobic exercise, hormone replacement therapy (HRT), and their interaction on carotid arterial compliance using a combination of cross-sectional and intervention study designs. METHODS: Cross-sectionally, we studied three groups of healthy postmenopausal women (50-80 years): 20 sedentary not taking HRT; 24 sedentary taking HRT; and 14 endurance-trained not taking HRT; and 11 sedentary premenopausal controls (20-37 years). In the intervention study, 12 sedentary postmenopausal women (58+/-3 years) who were taking HRT were studied before and after participation in a 3-month aerobic exercise (walking) program. Carotid arterial compliance was measured via simultaneous common carotid artery ultrasound imaging and applanation tonometry. RESULTS: Cross-sectional study. Carotid arterial compliance was lower (P<0.001) in all three postmenopausal groups compared with premenopausal women. Among the postmenopausal groups, arterial compliance was 33-43% higher in the sedentary HRT and endurance-trained women than in their sedentary estrogen-deficient peers. Intervention study. Arterial compliance increased (P<0.05) by approximately 40% to levels that were no longer different than premenopausal women. CONCLUSIONS: HRT use and regular aerobic exercise are associated with augmented carotid arterial compliance in healthy postmenopausal women. Moderate, short-term aerobic exercise can restore carotid arterial compliance in previously sedentary postmenopausal women taking HRT.     

Relationship between insulin-resistance and remnant-like particle cholesterol

We investigated the relationship between insulin-resistance (IR) and remnant-like particle cholesterol (RLP-C) using 472 subjects (174 men and 298 women) randomly selected from inhabitants of two rural communities in Japan, Tanno and Sobetsu. The level of fasting immunoreactive insulin (FIRI), fasting blood glucose (FBS), total cholesterol (TC), triglyceride (TG), HDL cholesterol, LDL cholesterol, and RLP-C were measured in each subject. Homeostasis model assessment (HOMA-R) was used as an indicator of IR. The subjects were divided into two groups according to the value of HOMA-R: an IR group of subjects with HOMA-R > approximately equal to 1.73 and a normal (NR) group of subjects with HOMA-R <1.73. There was a significant positive correlation between HOMA-R and RLP-C. The value of RLP-C was higher in the IR group than in the NR group (7.1 vs. 3.9 mg/dl in men and 5.3 vs. 3.6 mg/dl in women). The frequency of hyper RLP cholesterolemia (RLP-C > approximately equal to 7.5 mg/dl) was higher in the IR than in the NR group (23.7 vs. 6.6% in men and 20.3 vs. 6.6% in women). The results of multiple regression analysis showed that HOMA-R was closely related to RLP-C. The results of this study suggest that RLP-C is closely associated with IR syndrome.     

The upper turnover site in the reentry circuit of common atrial flutter

The upper turnover site of the reentry circuit of common AF is anterior to the orifice of the superior vena cava. The reentrant excitation wavefront seems to circulate along the entire tricuspid annulus around anatomic (i.e., orifices of superior and inferior vena cava) and functional obstacles between the orifices as proposed previously.¹⁸     

Cardiovascular impact of exercise and drug therapy in older hypertensives with coronary heart disease: PREHACOR study

Our aim in this study was to examine the relationship between regular exercise and major cardiovascular events in hypertensive elderly with established coronary heart disease (CHD) in the primary care setting. The PREHACOR study recruited 3193 hypertensive patients, aged 74 ± 6 years, 67% male, with CHD. Regular exercise assessed by questionnaire was defined as recreational activity >20 min/day, >3 times/week. Endpoints at 6 months were new cardiovascular events (NCEs: myocardial infarction and hospitalization for stroke, unstable angina, congestive heart failure, or coronary revascularization). New cardiovascular events occurred in 376 patients (11.8%), with 17 deaths (0.5%). New cardiovascular events patients were older, with higher body mass index, and were more likely to have diabetes, arrhythmia, history of congestive heart failure, and noncardiac organ damage than non-NCE patients. Blood pressure was significantly and similarly reduced in both groups. Multivariate logistic regression associated NCEs positively and independently with a history of congestive heart failure (odds ratio [OR] 2.50; confidence interval [CI] = 1.9–3.23), noncardiac target organ damage (OR 1.51; CI = 1.20–1.90), and beta-blocker use (OR 1.28; CI = 1.02–1.59), and inversely and independently with combination low-dose angiotensin converting enzyme inhibitor + diuretic therapy (OR 0.66; CI = 0.45–0.95) and regular exercise (OR 0.70; CI = 0.54–0.90). Regular exercise is significantly associated with fewer major cardiovascular events in hypertensive elderly subjects with established CHD.     

Treatment of bedsores--combination of therapies depended the experimental design method

The treatment of bedsores is a particular problem in geriatric medicine. We selected standard drugs that may be effective for the decubitus ulcer, and investigated combination therapy to develop efficient treatment The subjects were 16 patients in whom the grade of the bedsore was evaluated as II to IV according to the Shea's depth classification. Treatment was performed while all patients were on air mats. We selected drugs and treatment methods based on the previously established experimental design of Taguchi. Based on this, we created and adapted 16 different component combination treatment programs in accordance with the L16 rectangular cross table. The following component factors were adopted: A: types of covering substances on the wound surface (Elase ointment, isodine sugar, isodine gel solcoseryl ointment); B: Isalopan powder; C: Spray of 10 ml physiological saline containing 500 microg of prostaglandin (concentration 0.005%); D: daily number of treatments; and F: presence or absence of tapping. We serially measured the wound surface area as an index of the speed of wound healing, and measured the interval (day) until the area decreased to one half of the original size (T1/2, half life). We analyzed data on one combination treatment each in 16 patients. Analysis of variance of the above factors showed significant F values for factors A, B, D and F. The contribution rates for factors A, B, D and F were 37.84%, 8.47%, 14.98% and 13.81%, respectively. The error term (e) was 16.37%. Optimal results were seen in the groups in which solcoseryl ointment had been applied twice a day. In this study, prostaglandin, which had been anticipated to be effective, did not show any effects. The error term (e) suggests the presence of other healing factors including individual differences. Concerning this point, it well be necessary to examine a larger number of patients in the future. With ointment treatment alone, without using an air mat, it was confirmed that bedsore area reduction was extremely unstable. Decompression of the affected part may be a basic prevention factor and essential treatment of bedsores.