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We enrolled 196 patients with hypertension who were already being treated with free-drug combinations of angiotensin-II receptor blocker (ARB) and amlodipine. The free-drug combinations of ARB and amlodipine were replaced with the same dose of the fixed-dose combinations. The average home blood pressure (BP) in all patients receiving fixed-dose combinations was significantly lower than those receiving free-drug combinations (131 ± 10/75 ± 8 vs. 136 ± 11/77 ± 9 mm Hg, P < .01) accompanied with increasing drug adherence. After lowering BP by fixed-dose combinations, the costs for medications decreased by 31% over the 3 months.

A 63-year-old woman who had undergone aortic valve replacement (AVR) with a 22-mm Medtronic Hall valve in May 1994 was admitted to the authors' hospital in June 2006 with epigastric pain and nausea. She presented with sudden precipitous deterioration of hemodynamics under high-dose catecholamines, but this improved in ca. 10 min. Valve motion was observed with fluoroscopy for a brief period as prosthetic valve dysfunction was suspected. After 10 min, transient insufficiency in closure of the prosthetic valve was revealed. The patient was diagnosed with prosthetic valve malfunction and referred for an urgent operation. At surgery, pannus was identified at the left ventricular aspect of the prosthetic valve in the aortic position, and this directly restricted leaflet movement during the closing phase. The leaflet movement showed no consistent pattern, but normal movement and half-closure occurred regularly to generate a phenomenon in which alternating normal hemodynamics and low-output syndrome was observed. The patient underwent AVR with a 17-mm St. Jude Medical Regent valve, and was discharged without any complications.

Background: Population-based analysis shows that deaths from pulmonary embolism (PE) are increasing in the older age groups, but it is unclear to what degree PE contributes to death in different ages and gender., Methods and Results: Potential contribution factors for all PE and for critical PE (in which PE was the primary cause of death or the main diagnosis) were examined in 396,982 autopsy cases. For all PE, odds ratio (OR) in males was 0.61 (95% confidence interval (CI) 0.59-0.64, p<0.0001), compared with that in females. ORs were 1.10 (95% CI 1.05-1.14, p<0.0001) in 1991-1994 and 1.19 (95% CI 1.14-1.25, p<0.0001) in 1995-1998, compared with those in 1987-1990. ORs for ages 0-9 and 40+ were significantly low compared with that for ages 20-39. For critical PE, similar results were obtained. Pregnancy and/or delivery were found in 38.5% in cases of critical PE in females aged 20-39., Conclusion: Compared with other age groups, PE contributed more to deaths in those aged 20-39 years. In recent years, deaths from PE have been slightly but significantly increasing. The incidence of clinically diagnosed critical PE also has been increasing.

Background: Septic and amniotic fluid emboli are rare sources of pulmonary embolism (PE), so the present study sought to elucidate the background of these cases., Methods and Results: A total of 11,367 PE cases were identified from 396,982 postmortem examinations. The incidence of septic PE was 247 (2.2%) of the total. The origin of infection was found in 85.6% of the cases. Fungal embolus was detected more often than bacterial embolus. The most frequently detected fungus was aspergillus (20.8%). The primary disease associated with fungal embolus was leukemia (43.2%). The incidence of PE cases associated with pregnancy and/or delivery was 89 (0.8%) of the total PE cases. Among them, amniotic fluid embolism was found in 33 (73.3%) of 45 PE cases with vaginal delivery, and in 7 (21.2%) of 33 PE cases with cesarean delivery (p<0.0001)., Conclusion: Fungal embolus was more frequent than bacterial embolus, and leukemia was most frequent as the primary disease in cases of fungal embolus. The main cause of PE in cesarean section cases was thrombotic embolism, and the main cause in vaginal delivery cases was amniotic fluid embolism.

Background: The specific incidence of thrombotic pulmonary embolism (PE), tumor PE and tumor invasion into large veins according to tumor type and tumor site remains unclear., Methods and Results: A total of 65,181 cancer patients were identified from 98,736 postmortem examinations. Thrombotic PE occurred in 2.32% of all cancer patients and comprised 88.6% of the total number of all PE events. The incidence of thrombotic PE was high in those with adenocarcinoma, leukemia and large cell carcinoma, and was low in those with hepatic cell carcinoma. The incidence of PE was high when tumor was present in hematogenous tissue, lungs, ovaries, pancreas and the biliary system, and was low when tumor was present in the liver. The incidence of tumor PE was high with large cell carcinoma, hepatic cell carcinoma and adenocarcinoma, and was also high when tumor was present in the lungs, ovaries, kidneys and liver. There was a significant correlation between the incidence of tumor PE and the incidence of tumor invasion into large veins., Conclusion: The incidence of thrombotic PE, tumor PE and tumor invasion into large veins varies significantly according to tumor histopathology and tumor site.

Background: The recognition of the trigger which is the action leading to the occurrence of acute pulmonary thromboembolism (APTE) is important to perform early diagnosis and early management of APTE., Methods and Results: The trigger of APTE in 138 patients who developed APTE in hospital was investigated. The triggers of APTE were specified in 57 patients. Approximately half of these patients developed APTE during toilet activities (defecation and micturition). Mortality of the patients with APTE associated with toilet activities was 33%. APTE associated with toilet activities was independently related to a recent major surgery, heart diseases and a recent angiography., Conclusions: Defecation and micturition would be common triggers of APTE after operation and angiography, especially in patients with cardiac dysfunction.

The utility of thrombolysis in patients with acute pulmonary thromboembolism (APTE) remains controversial, although anticoagulation therapy for APTE is well-established in Western countries. Nonetheless, large clinical trials of antithrombotic treatments for APTE have yet to be performed in Japan. In the present study, the association between antithrombotic treatments (thrombolysis and anticoagulation) and the clinical outcomes was retrospectively investigated in 225 APTE patients. In-hospital mortality was significantly lower in hemodynamically stable patients who received anticoagulation therapy than in those who received no adequate therapy (0% vs 33%). Thrombolysis in patients with or without cardiogenic shock failed to improve the in-hospital outcomes compared with those who received anticoagulation treatment (8% vs 3%). There was no significant difference in the bleeding rate between patients receiving thrombolysis and anticoagulation (3% vs 3%). These results indicate that anticoagulation could reduce the mortality of hemodynamically stable APTE patients and that the outcome after thrombolysis or anticoagulation treatment was similar. However, this study was limited because it was executed retrospectively. Further prospective randomized trials to investigate the efficacy of thrombolysis in Japan should be performed to completely address this issue.

Aim: In Japan, acute pulmonary thromboembolism (APTE) is still rare, but the number of patients with APTE has been steadily increasing. It is important for early diagnosis and early management of APTE to recognize epidemiological characteristics of this condition., Methods: We investigated the epidemiological characteristics of 252 patients with APTE who were admitted to our institutions between 1975 and 2001. APTE was more prevalent in women that in men. It was observed the most in the age group between 50s to 70s, especially in women. Many patients had prolonged immobilization, recent major operation, obesity, or cancer, as risk factors for venous thromboembolism. One hundred and thirty-eight patients developed APTE in hospital; 60 patients were in Department of Internal Medicine, 28 in General Surgery, 15 in Orthopedics, 15 in Obstetrics and Gynecology, and 20 in other services., Results: Among 58 patients with malignancy, 43% had cancers in digestive organs, 21% in gynecological, and 17% in urological. Among 61 patients who were examined for the presence of thrombophilia, 13 patients had inherited thrombophilia (8 protein C deficiency, 4 protein S deficiency, and 1 antithrombin III deficiency) 11 had antiphospholipid antibodies which indicated thrombophilia. Five out of the above 61 patients (8%) had no obvious risk factors including thrombophilia., Conclusion: The findings in our patients were almost the same as those in Western patients, except for some points. These results might be useful to establish a preventive approach for APTE in Japan.

Objectives: To evaluate the feasibility, effectiveness and complications of the retrievable vena cava filter [Güther tulip vena cava filter(GTF)] for the prevention of pulmonary thromboembolism in patients with deep vein thrombosis., Methods: Seventeen patients, 3 males and 14 females, aged 21 to 82 years (mean age 59 +/- 19 years), underwent implantation of GTFs between December 2000 and February 2002 at Mie University Hospital. All patients were treated under diagnoses of deep vein thrombosis with or without pulmonary thromboembolism based on venous ultrasonography, venography or computed tomography. Eleven patients were treated with thrombolysis., Results: Significant thromboembolus was trapped within the filter in 3 of 12 patients. No acute pulmonary thromboembolism occurred during implantation or at retrieval of the GTF. Retrieval of the GTF was attempted in 9 patients, and 8 GTFs were retrieved successfully. Mean interval of the filter implantation was 13.4 +/- 6.3 days and the mean retrieval time was 4.8 +/- 3.2 min. No complications occurred except for one case of minor hemorrhage at the puncture site., Conclusions: The placement and retrieval of the retrievable vena cava filter was feasible and safe. This filter was also effective for the prevention of pulmonary thromboembolism. This retrievable vena cava filter may be a good first-choice filter for both permanent and temporary use.

Despite the advances in our understanding of venous thromboembolic disease, the prevalence of pulmonary thromboembolism (PTE) at autopsy has not changed over 3 decades. When patients survive long enough to have a diagnosis of massive PTE and start receiving treatment, the outlook is considered to be moderately good. However, the diagnosis is often difficult to obtain and is frequently missed. We hypothesize that mortality of acute PTE is reduced by early diagnosis. Eighty-five patients with acute PTE with circulatory failure who survived 1 h after the onset were divided into two groups: the early Dx group consisted of the patients whose disease was diagnosed as acute PTE within 24 h of the onset, and the Late Dx group included patients whose disease was not diagnosed within 24 h of onset, or died without clinical diagnosis between 1 and 24 h after the onset. Overall mortality was significantly low in the Early Dx group compared with that of the Late Dx group (21.6% vs 67.6%, P < 0.0001). Multiple logistic regression analysis demonstrated that a reduction in in-hospital mortality was associated with early diagnosis (odds ratio for in-hospital death, 0.094; 95% confidence interval, 0.03-0.33). The results of our study suggested that early diagnosis might favorably affect the in-hospital clinical outcome of hemodynamically unstable patients with acute PTE.

Objective: In this prospective, non-controlled observational study, we evaluated the middle- to long-term results of placement of inferior vena cava (IVC) filter devices in Japanese patients., Methods and Results: In 42 Japanese patients with deep vein thrombosis (DVT) or pulmonary thromboembolism (PTE) who underwent percutaneous insertion of IVC filters, follow-up examinations at fixed intervals of 2 years were performed, and the data was evaluated including complications. There were no fatal complications during IVC filter implantation. About 5% of patients with an inserted IVC filter developed symptomatic PTE, another 5% developed asymptomatic PTE. The trapped thrombus was demonstrated in about 22% of the inserted IVC filters. Lower rates of PTE development, occlusion of IVC, and captured thrombus were found in the cases where concurrent use of anticoagulation therapy with filters was used. Trapped thrombi were found in half of IVC filters inserted prophylactically for proximal femoral venous thrombosis., Conclusion: These experiences with IVC filters suggest that they are safe and effective for the prevention of PTE in the Japanese population.

36-year-old-female admitted because of jaudice and ascites. T-bil was 18.5 mg/dl and transaminase, ALP, LDH and gamma-GTP was elevated. Ultrasonography (US) showed that right lobe was atrophy and left lobe was swelling. Plain computed tomography (CT) showed right lobe was low density. Magnetic resonance (MR) finding was T1-weighted image of right lobe was low intensity and T2-weighted image was high intensity. Angiography showed right lobe was more stained than left lobe. Histologically, right lobe was massive necrosis. These findings suggested that right lobe was liver scar. Biliary imaging showed right lobe was delayed. A 23-year-old-female admitted because of fever and abdominal tumor. Transaminase was normal, only gamma-GTP was elevated. US, plain CT, enhanced CT, MR imaging finding was as same as that of the first case. Similarily, biliary scintigraphy showed right lobe was delayed. Causes of the two liver scars was not clear, whereas liver scar detected after delivery was rare case.

We describe an autopsy case of severe intracranial hemorrhage which occurred during the infusion of tissue plasminogen activator (t-PA) for acute myocardial infarction. A 75-year-old man was admitted with substernal chest pain of 3-h duration and electrocardiographic changes consistent with an acute inferior myocardial infarction. Physical examination was unremarkable, except for an initial blood pressure reading of 160/96 mmHg. The patient received 3,000 IU intravenous heparin followed by a 2.4 x 10(6) IU bolus dose of tissue plasminogen activator (t-PA) (Alteplase). This was followed by a drip infusion of 21.6 x 10(6) IU of t-PA over 1 h (total dose 41 mg). Thirty minutes after the infusion of t-PA was initiated, the patient suddenly lost consciousness and began to have violent convulsions, followed by cardiac arrest. Autopsy revealed massive hemorrhage in the bilateral cerebrum and brain stem. To our knowledge, this is the first case of sudden death during t-PA infusion therapy.

Although it is well known that diabetics have high mortality rates due to ischemic heart disease (IHD), controversies still exist about the severity of coronary artery disease in diabetics compared to nondiabetics. We compared coronary arteriographies of 50 diabetics with IHD to those of 50 nondiabetics with IHD. In regard to coronary risk factors, incidence of obesity was significantly higher in diabetics. Incidence of hypertension, hypercholesteremia, hyperuricemia was higher, although not significant, in diabetics. Incidence of smoking was significantly higher in nondiabetics. The diabetic group showed a significantly higher incidence of patients with more than two or three diseased vessels, and a significantly higher number of diseased coronaries with more than 50% stenosis per patient compared to nondiabetics (5.6 +/- 3.7 vs 3.7 +/- 3.2). The distribution of diseased coronaries with more than 75% stenosis showed no difference between diabetics and nondiabetics. The incidence of coronary spasm was significantly lower in diabetics (12% vs 28%). The high incidence of multiple vessel disease in diabetics was thought to be due to other complicated coronary risk factors, especially hypertension and hypercholesteremia.

A case was presented in which a rare T wave alternans occurred in association with congenital long QT syndrome. A 71-year-old woman, who had experienced several syncopal attacks per year for the previous forty years, was admitted for further evaluation of the syncope. She had a family history of sudden death (sister) and QT prolongation (son). Electrocardiogram showed a corrected QT interval of 0.68 seconds. Treadmill exercise-tolerance test revealed both T wave alternans immediately after exercise and torsades de pointes 150 seconds after exercise. The syncope was induced by the mental excitation. A prolonged corrected QT interval reduced from 0.70 seconds to 0.58 seconds by the correction of her serum potassium and magnesium. The effect of propranolol, verapamil, phenytoin or mexiletine on T wave alternans and ventricular arrhythmia was evaluated by the treadmill exercise-tolerance test. The treatment with propranolol was most effective.

A 72-year-old man with recurrent pancreatitis and a horseshoe-shaped anomaly of the pancreas is described. The diagnosis was made by endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography scan; laparotomy was confirmatory. The abnormal duct branched to the lower left from an enlarged Santorini's duct; a thin Wirsung's duct was joined at its distal portion to the junction of the abnormal duct. The anomaly was associated with a cystic dilatation of the common bile duct with stone and cholecystolithiasis. This anomaly is considered to be a variation of the dominant dorsal duct syndrome.

We investigated the effects of verapamil and diltiazem on cytosolic free calcium and amylase secretion in rat pancreatic acini. Verapamil and diltiazem reduced a rise in cytosolic free calcium and amylase release stimulated by the maximal concentration (10(-5) M) of carbachol in a dose-dependent manner. High concentrations (500 microM) of verapamil and diltiazem inhibited both the initial and the sustained amylase secretion stimulated by 10(-5) M carbachol. However, at low concentration (1 microM), they showed no effect on amylase secretion by 10(-5) M carbachol. These calcium-channel blockers did not affect calcium mobilization and amylase secretion stimulated by either caerulein or neuromedin C. Binding of 3H-N-methylscopolamine to pancreatic acini was inhibited by verapamil and diltiazem in a dose-dependent manner. These findings suggested that verapamil and diltiazem reduced carbachol-induced amylase secretion probably not due to their calcium-channel blocking activities but due to their non-competitive effects on the level of muscarinic receptors.

The alteration of CCK receptor binding on the pancreatic acini in vitro following the induction of pancreatitis was investigated in male rats. Pancreatitis was induced by administering 5 intraperitoneal injections of caerulein, 40 micrograms/kg each at hourly intervals. The uptake of [3H]-thymidine in the pancreatic acini increased on day 7 following caerulein administration. The release of amylase stimulated by CCK-8, and CCK receptor analysis using bioactive [125I]-BH-CCK-8, were performed at regeneration stage, on days 14 and 28 following the injections. The maximal release of amylase stimulated by CCK-8 was reduced on day 14 by about 40% and recovered on day 28. On day 14 there was a decrease of 60% in the number of high-affinity receptors and an increase of 161% in the number of low-affinity receptors. On day 28 there was a 128% increase in the number of low-affinity receptors. Accordingly, we suggest that the CCK receptors of the regenerating cells following caerulein-induced pancreatitis differ from those of the intact cells.

Of 100 cases of chronic pancreatitis, 20 received surgical treatment. The duration of illness before surgical treatment was less than 5 years in 75% of patients. Post-operatively, the persistent abdominal pain was relieved and serum pancreatic enzyme levels were normalized in all the patients except two who continued drinking alcohol. Exocrine and endocrine pancreatic function were unchanged or slightly improved post-operatively in most cases. In 9 of 10 patients who have been followed up post-operatively for over 4 years, pancreatic endocrine function has been maintained by diet control with no significant impairment of glucose tolerance. These results suggest that in patients with chronic pancreatitis surgical intervention is of greatest benefit in preservation of pancreatic functions when it is performed at an early stage in which these functions are relatively well maintained.