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.     

LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Congenital quadricuspid aortic valve with tetralogy of Fallot and pulmonary atresia

We report the case of a 4-year-old girl who had quadricuspid aortic valve regurgitation with tetralogy of Fallot and pulmonary atresia. This combination is very uncommon. Aortic valve replacement was performed successfully due to aortic regurgitation which had progressed one year after the total repair. The dilated aortic annulus plus quadricuspid aortic valve may result in progressive aortic regurgitation for a short period.     

Clinico-pathological comparative study between brainstem encephalitis of Iizuka type and neuro-Beh?et's disease

We experienced one necropsy case of brainstem encephalitis of Iizuka type (BSE) and one necropsy case of the brain-stem syndrome (BSS) of typical neuro-Beh?et's disease, and compared them clinically and neuropathologically. Clinically both of these cases showed chronic progressive mental disturbance, pseudobulbar paresis, spastic tetraparesis, cerebrospinal fluid pleocytosis, increased protein, and brainstem atrophy observed by X-CT. Neuropathologically, irregular, boundary-indistinct demyelinating lesions and obsolete softening lesions were sporadically found, associated with perivascular lymphocytic infiltration and gliosis centering on the brainstem. In this way, both cases were similar in many points except for the presence or absence of cutaneo-muco-ocular signs specific for Beh?et's disease. Also BSE and BSS reports in the literature showed that both diseases were similar not only in clinical findings consisting of mental disturbance and brainstem signs but also in neuropathological findings with similar topographical distribution of the same histopathological changes, including the variations and diversity of these characteristics. Especially of much interest is their similarity in characteristic mental disturbance. In discriminating BSE from multiple sclerosis and other diseases with exclusive involvement of the brainstem, it is important to understand their clinical characteristics. The characteristic mental disturbance includes damage to memory and sentiment, a change in personality, and lowering in spontaneity, but calculation ability and orientation are comparatively preserved. Of course the similarity in clinical and neuropathological findings does not necessarily mean the identical etiopathogenesis. However, it is possible to consider that neuro-Beh?et's disease (syndrome) may form a wide spectrum with BSE and typical neuro-Beh?et's disease at the both ends, regarding the time and spatial diversity of the appearance of cutaneo-muco-ocular signs.     

Quantitative and qualitative changes of apolipoprotein AI-containing lipoproteins in patients on continuous ambulatory peritoneal dialysis

Using immunoaffinity chromatography, two species of apo-AI containing lipoproteins (AILp); lipoprotein containing apo-AI and apo-AII (Lp-AI/AII), and lipoprotein containing apo-AI, but no apo-AII (Lp-AI) were isolated from 13 female patients on continuous ambulatory peritoneal dialysis (CAPD), then characterized. The results were compared with findings obtained in agematched normolipidemic (control I) and mild hypertriglyceridemic (control II) female subjects. In comparison with control I: In AILp, the levels of total cholesterol (TC), cholesteryl ester (CE) and phospholipid (PL), and the levels of apoE were significantly lower in the CAPD patients while the levels of triglyceride (TG) and apo-CIII were significantly higher in these patients. The levels of apo-AI and apo-AII did not differ between the CAPD and control subjects. In Lp-AI/AII, changes of TC, CE, PL, TG, and apolipoproteins were similar to those of AILp, except for the ratio of apo-AI/apo-AII and the level of apo-CII, which was higher in the CAPD patients. In Lp-AI, changes of TC, CE, PL, and TG were also similar to those of AILp and Lp-AI/AII, but the apo-AI level was significantly lower in the CAPD patients. In comparison with control II: In AILp, the levels of PL, apo-AI, apo-AII, and apo-E were significantly lower in CAPD patients, but the apo-CIII levels were significantly higher. In Lp-AI/AII, the levels of PL and apo-E were significantly lower in CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Two surgically cured cases of subependymoma with emphasis on magnetic resonance imaging

The authors describe two surgically cured cases of symptomatic subependymomas located in the lateral ventricle and septum pellucidum with emphasis on magnetic resonance imaging study. Both computed tomography and MRI revealed a calcified mass with repeated intratumoral hemorrhages. Cerebral angiograms disclosed rather hypovascular lesions. The histologic diagnosis was proven to be of subependymoma. The pertinent literature of surgically treated subependymomas is reviewed, and the characteristic biologic features are also discussed.     

REOPERATION FOR RECURRENT CORONARY ARTERY DISEASE: RESULTS OF 200 CONSECUTIVE CASES

Background : It is well known that reoperation for recurrent coronary artery disease is more difficult than primary coronary artery bypass grafting. However, it is possible to reduce the morbidity and mortality of reoperation to the same level as the initial procedure with careful surgical technique. Methods : A retrospective study of the first 200 patients who underwent redo coronary bypass grafting was undertaken. Results : In the first 200 cases of redo coronary bypass grafting at St George Hospital, Sydney (August 1986–January 1995), there were five in-hospital deaths (2.5%). There was one case of sternal infection (0.5%), which required surgical debridement, three cases of stroke (1.5%), one case of postoperative bleeding (0.5%), which required a return to theatre and six cases (3%) required mechanical ventilation for more than 24h. The need for major postoperative support (such as intra-aortic balloon pumping/adrenaline infusion) was significantly affected by the degree of urgency and the degree of pre-operative ventricular impairment. Conclusions : The mortality rate of redo coronary artery bypass grafting in this series is similar to that of primary surgery described in other reports.