Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme.

Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2.     

Prostaglandin el attenuates impairment of cellular immunity after cardiopulmonary bypass

OBJECTIVE: It is well documented that cardiopulmonary bypass (CPB) severely impairs cellular immunity. The objective of this study was to investigate the effect of prostaglandin E1 (PGE1) on cellular immunity after CPB. METHODS: Patients who underwent elective cardiac surgery were randomly divided into the PGE1 group (n=12) and the control group (n=12). In the PGE1 group, PGE1 was administered at 20 ng/kg/min from just after the induction of anesthesia to the end of surgery. Peripheral blood mononuclear cells (PBMCs) were taken before anesthesia and on postoperative days 1, 3 and 7 (POD 1, POD 3 and POD 7). Proliferation responses of T cells to phytohemagglutinin (PHA) and pure protein derivative (PPD) antigen were measured as indicators of cellular immunity. RESULTS: PGE1 significantly attenuated the impairment of both PHA and PPD response after cardiac surgery on POD 1 (PHA response, 30 +/- 21% vs. 53 +/- 32%, control vs. PGE, p=0.048; PPD response, 18 +/- 21% vs. 39 +/- 27%, control vs. PGE, p=0.046). The reduced glutathione content of PBMCs in the control group was significantly decreased on POD 1. CONCLUSION: PGE1 attenuated the impairment of cellular immunity after cardiac surgery with CPB by reducing oxidative stress on PBMCs.     

IMPROVED BALLOON‐TIPPED TRANS‐ANAL ILEUS TUBE

Background: For management of bowel obstruction due to colorectal cancer, endoscopic trans‐anal decompression technique has been first reported by Lelcuk et al. in 1986 using balloon dilatation technique. Since then, various types of trans‐anal decompression tubes have been clinically used for patients suffering from left side obstructing colorectal cancer as an emergent decompressing device. At present, two types of trans‐anal ileus tube (trans‐anal decompression tube) have been available for clinical use, but they have two main problems that are late colon perforations caused by the tip of the tube and tube obstruction by stool. Methods: Analysis on three late colon perforations experienced with the use of conventional devices drew possible improvements to make a trans‐anal ileus tube less harmful. To overcome the pitfalls inherent to conventional tubes, the author has developed an improved trans‐anal ileus tube with a balloon installed at the very end of the tube (‘balloon‐tipped type’) made of silicone, measuring 1200 or 1700 mm in total length and 22 Fr in outer diameter. It has been used for 12 cases with obstructing colorectal cancer etc. and its outcomes were compared with those obtained by the use of conventional trans‐anal ileus tube. Results: No late perforations have been encountered, but tube obstruction did occur in one of 12 cases. Conclusion: The new trans‐anal ileus tube with a balloon installed at the tip of ileus tube is considered to be safer and especially effective in preventing late colon perforation and tube obstruction.     

Regional effects of craniotomy on cerebral circulation and metabolism: PET study on the un-ruptured aneurysmal surgery

Regional effects of craniotomy on cerebral circulation and metabolism, such as regional cerebral blood flow (rCBF), regional cerebral oxygen consumption (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) were examined by a PET (positron emission tomography) study concerning surgery that was performed on unruptured aneurysm patients. Eight patients with intracranial un-ruptured aneurysms were studied pre- and post-operatively by the 15O labelled-gas steady-state method, using HEADTOME-III. All patients underwent aneurysmal surgery performed by the transsylvian approach. There was a significant increase in the mean OEF values taken from the whole-brains of 8 patients, but there was not a significant change in CBF, CMRO2 or CBV. The increase in OEF was caused by decrease of O2 content, which was caused by post-operative decrease in the Hb value. So, this OEF increase was not the direct effect of craniotomy. In 2 patients, the rCBF and rCMRO2, in the fronto-temporal region (where craniotomy was performed) increased post-operatively. This regional effect suggests transient reactive hyperemia following compressive ischemia during the operative procedure, and metabolic demands for recovery of brain function. In 2 other patients, who had relatively low rCBFs during the pre-operative study, rCBF and rCMRO2 in the bi-frontal region had decreased more at the post-operative study. This change appears to have been caused by removal of cerebrospinal fluid and depression of the frontal lobe. From this study, it becomes evident that the regional effect of craniotomy on cerebral circulation and metabolism is not so great, when adequate microsurgical techniques are used.     

Effect of diltiazem on coronary blood flow distribution in dog heart under ischemia

Effect of intracoronary infusion of diltiazem (1 microgram/min) on regional myocardial blood flow (RMBF) was studied using 15-microns radioactive microspheres in 11 excised cross-circulated canine left ventricles. With total coronary blood flow (CBF) and heart rate (HR) held constant, regional ischemia was induced by ligating the left anterior descending coronary artery (LAD). Diltiazem at the dose used had no effects on ventricular Emax before and after LAD ligation. RMBF expressed by the counts divided by the counts averaged in all segments in each layer significantly (p less than 0.05) increased under diltiazem only in the low-flow region that had less than 50% RMBF before diltiazem; from 21% (+/- 12%) to 35% (+/- 18%) in the epicardial, from 22% (+/- 12%) to 32% (+/- 18%) in the midwall, and from 24% (+/- 10%) to 31% (+/- 12%) in the endocardial layers. We conclude that the beneficial effect of diltiazem on the ischemic heart involves a direct action on the coronary vascular system and does not necessarily depend on the concomitant changes in hemodynamics.     

The correlation of the treadmill exercise test with cardiac hemodynamics in patients with previous myocardial infarction

The correlation between the treadmill exercise test results and the hemodynamic data of 152 patients with previous myocardial infarction were investigated. The patients were classified into 4 groups as follows: H1 left ventricular end-diastolic pressure (LVEDP) less than or equal to 12 mmHg and cardiac index (CI) greater than or equal to 3.0 L/min/m2; H2 LVEDP greater than 12 mmHg and CI greater than or equal to 3.0 L/min/m2; H3 LVEDP less than or equal to 12 mmHg and CI less than 3.0 L/min/m2; and H4 LVEDP greater than 12 mmHg and CI less than 3.0 L/min/m2. The duration of the exercise was significantly shortened for group H4 than group H1 (p less than 0.01). The maximal ST segment elevation (mSTe) was significantly increased for group H3 and group H4, versus group H1 (p less than 0.05). The number of ST segment elevations and mSTe/maximal heart rate were significantly increased for group H3 (p less than 0.05) and group H4 (p less than 0.01) versus group H1. The incidence of exercise-induced premature ventricular contractions (PVCs) was significantly increased in group H3 and group H4, versus group H1 (p less than 0.05). There were no significant differences in the maximal heart rate, double product, and ST segment depression among the 4 groups. Our data indicate that the groups with impaired left ventricular functions tend to decrease the duration of the exercise and to increase ST segment elevation and PVC frequencies during exercise.     

A case of pulmonary artery bypass surgery for a patient with isolated Takayasu pulmonary arteritis and a review of the literature.

A 45-year-old female was presented with progressive dyspnea and bilateral leg edema. Pulmonary angiography revealed total occlusion of the right pulmonary artery and significant stenosis of the left pulmonary artery. The inferior lobar artery as well as the segmental arteries were well patent. No pathology was detected elsewhere at the aorta and its branches. The diagnosis of chronic pulmonary arterial occlusion by isolated Takayasu arteritis was made because of the characteristic pattern of angiographic findings and the presence of unusual shunt formation from the coronary artery to the peripheral portion of the pulmonary artery, as well as a characteristic presentation of HLA typing in blood analysis, which strongly suggested the diagnosis of Takayasu arteritis. To restore the pulmonary blood flow, we employed reconstructive surgery by means of bypass procedure, using PTFE graft. Postoperatively there was marked improvement in cardiopulmonary function and the quality of life of the patient. The graft was proved to be patent at long-term follow-up study. An extremely rare case of chronic occlusive pulmonary arteritis, which was surgically treated by means of bypass procedure, is reported herein, and a brief review of previous reports on this subject was attempted.     

Treatment strategy for synchronous metastases of colorectal cancer: is hepatic resection after an observation interval appropriate?

Background In cases of synchronous colorectal hepatic metastases, the primary colorectal cancer strongly influences on the metastases. Our treatment policy has been to conduct hepatic resection for the metastases at an interval of 3 months after colorectal resection. We examined the appropriateness of interval hepatic resection for synchronous hepatic metastasis. Materials and methods The subjects were 164 patients who underwent resection of hepatic metastasis of colorectal cancer (synchronous, 70 patients; metachronous, 94 patients). Background factors for hepatic metastasis and postoperative results were compared for synchronous and metachronous cases. Results The cumulative survival rate for 164 patients at 3, 5, and 10 years postoperatively was 71.9%, 51.8%, and 36.6%, and the post-resection recurrence rate in remnant livers was 26.8%. Interval resection for synchronous hepatic metastases was conducted in 49 cases after a mean interval of 131 days. No difference was seen in postoperative outcome between synchronous and metachronous cases. Conclusion The outcome was similarly favorable in cases of synchronous hepatic metastasis and in cases of metachronous metastasis. Delaying resection allows accurate understanding of the number and location of hepatic metastases, and is beneficial in determining candidates for surgery and in selecting surgical procedure.     

Pancreatic metastasis of malignant melanoma diagnosed by EUS-guided fine needle aspiration (EUS-FNA)]

Pancreatic metastasis of malignant melanoma is rarely diagnosed while the patient is alive. We report a case of metastatic melanoma of the pancreas in a 35-year-old woman presenting with a solid mass of the pancreas. Her past medical history included a radical hysterectomy 2 years previously for malignant melanoma of the vagina. Twelve months later, lung metastasis was also resected. EUS-guided fine needle aspiration (EUS-FNA) identified that the pancreatic tumor was histologically and immunohistochemically identical to the surgical specimen of her lung neoplasm. Imaging studies including US, CT, and MRI have limited value to distinguish the tumors from primary ductal adenocarcinoma. EUS-FNA can provide tissue diagnosis from pancreatic masses, specifically when other modalities have failed.