Aliskiren, a novel oral renin inhibitor, provides dose-dependent efficacy and placebo-like tolerability in Japanese patients with hypertension.

Aliskiren is a novel orally active renin inhibitor for the treatment of hypertension. This study evaluated the antihypertensive efficacy, safety and tolerability of aliskiren in Japanese patients with hypertension. Forty hundred and fifty-five Japanese men and women with a mean sitting diastolic blood pressure of 95-110 mmHg were randomized to receive once-daily double-blind treatment for 8 weeks with aliskiren 75, 150 or 300 mg or placebo. Aliskiren produced significant, dose-dependent reductions in mean sitting diastolic blood pressure (p<0.0005 vs. placebo for each dose) and mean sitting systolic blood pressure (p<0.001 vs. placebo for each dose). The placebo-corrected reductions in mean sitting systolic/diastolic blood pressure were 5.7/4.0, 5.9/4.5 and 11.2/7.5 mmHg in the aliskiren 75, 150 and 300 mg groups, respectively. After 8 weeks' treatment, 27.8%, 47.8%, 48.2% and 63.7% of patients in the placebo and aliskiren 75, 150 and 300 mg groups, respectively, achieved a successful treatment response (diastolic blood pressure <90 mmHg and/or reduced by > or =10 mmHg from baseline; p<0.005 vs. placebo for each dose). Aliskiren treatment was well tolerated, with the incidence of adverse events reported in the active treatment groups (53-55%) being similar to that in the placebo group (50%). This study, which is the first to assess the antihypertensive efficacy and safety of aliskiren in Japanese patients with hypertension, demonstrates that the once-daily oral renin inhibitor aliskiren provides significant, dose-dependent reductions in blood pressure with placebo-like tolerability.     

Crohn's ileocolitis with initially superimposed cytomegalovirus infection, resembling intestinal tuberculosis]

We describe a case of 41-year-old Japanese man with Crohn's ileocolitis and cytomegalovirus infection, confirmed by histology of ileal ulcers. Although his colonoscopic and radiological features resembled those of intestinal tuberculosis, granulomas of typical Crohn's disease were evident on histology of biopsy specimens taken from the duodenum and colon. The lesions remain unchanged even after 1.5 years by oral administration of salazosulphapyridine 3g daily.     

Effects of hypertension and type 2 diabetes mellitus on the risk of total cardiovascular events in Japanese patients with hypercholesterolemia: implications from the Japan Lipid Intervention Trial (J-LIT).

Hyperlipidemia, hypertension, and diabetes mellitus (DM) are well-established risk factors for cardiovascular disease. We analyzed the cardiovascular events in hyperlipidemic patients with or without DM who were administered open-labeled simvastatin in groups stratified by blood pressure level using data from the Japan Lipid Intervention Trial (J-LIT). Hyperlipidemic patients with DM (n=6,288) had significantly more cardiovascular events than those without DM (n=33,933). The incidence rates of total cardiovascular events in the Non-DM and DM groups were 15.40 and 25.76 per 1,000 patients for the 6-year period, respectively. The relative risk of total cardiovascular events in the DM vs. the Non-DM group was 1.68, and the relative risk was significantly higher in the DM than in the Non-DM group. The relative risks of total cardiovascular events were significantly higher in DM and Non-DM patients whose systolic blood pressure (SBP) was greater than or equal to 130 mmHg compared to that of Non-DM patients whose SBP was less than 130 mmHg, and in DM and Non-DM patients whose diastolic blood pressure (DBP) was greater than or equal to 80 mmHg compared to that of Non-DM patients whose DBP was less than 80 mmHg. In all groups stratified by SBP and DBP, relative risks of total cardiovascular events were higher in DM patients than in Non-DM patients. For patients with hypercholesterolemia and DM, blood pressure should be strictly controlled in order to prevent both coronary events and stroke. These results are in good agreement with the JNC 7 and the ESH/ESC guidelines for DM patients, which recommended that the SBP and DBP be less than 130 and 80 mmHg, respectively.     

Successful embolization of a large superior gluteal artery pseudoaneurysm emerging during anticoagulant therapy

Gross hemorrhage is the most serious complication of anticoagulant therapy. We report the discovery and treatment of a large pseudoaneurysm of the superior gluteal artery in one patient who had been receiving oral anticoagulant therapy. We diagnosed the pseudoaneurysm by contrast-enhanced computed tomography, and embolized the artery with stainless steel coils. The exact cause of the pseudoaneurysm remains unclear, however, minor trauma appears most likely.     

Detection of Platelet Antibody Using Rosette Technique with Anti-IgG Antibody-Coated Polyacrylamide Gel

Abstract. Paraformaldehyde-fixed platelets from normal donors were used for detection of antibody to platelet by in vitro sensitization (indirect method) utilizing rabbit anti-human IgG heavy chain specific antibody-coated polyacrylamide gels (Immunobeads). The sensitized platelets formed rosettes with Immunobeads and the positive rosette count was over 30%, while control showed less than 8% when normal sera were used. This method was also applicable for detecting antibody-sensitized platelets in vivo (direct method) in patients with autoimmune thrombocytopenia. This method is simple, rapid and reproducible for clinical use. Direct and indirect immunofluorescent antibody tests and a blocking test with anti-human serum also supported the results of Immunobead rosetting technique.     

Pigmented squamous cell carcinoma of the uterine cervix.

A 57-year-old female presented with an abnormal Pap smear. Colposcopic examination of the cervix revealed white mucosa with erosion and several areas of black pigmentation. After a colposcopically directed biopsy and loop conization, radical hysterectomy and bilateral salpingo-oophorectomy with pelvic and paraaortic lymphadenectomy were performed. Pathological examination disclosed an invasive squamous cell carcinoma admixed with many dendritic melanocytes. Melanin granules were present within the melanocytes and tumor cells. Although similar tumors have been reported in other sites, this is the first report to our knowledge of a pigmented squamous cell carcinoma of the uterine cervix.     

Increased expression of gp91phox homologues of NAD(P)H oxidase in the aortic media during chronic hypertension: involvement of the renin-angiotensin system.

Although vascular cells express multiple members of the Nox family of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, including gp91phox, Nox1, and Nox4, the reasons for the different expressions and specific roles of these members in vascular injury in chronic hypertension have remained unclear. Thus, we quantified the mRNA expressions of these NAD(P)H oxidase components by real-time polymerase chain reaction and evaluated superoxide production and morphological changes in the aortas of 32-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar Kyoto rats (WKY). The aortic media of SHRSP had an approximately 2.5-fold greater level of Nox4 mRNA and an approximately 10-fold greater level of Nox1 mRNA than WKY. The mRNA expressions of gp91phox and p22phox in SHRSP and WKY were comparable. SHRSP were treated from 24 weeks of age for 8 weeks with either high or low doses of candesartan (4 mg/kg/day or 0.2 mg/kg/day), or a combination of hydralazine (30 mg/kg/day) and hydrochlorothiazide (4.5 mg/kg/day). The high-dose candesartan or the hydralazine plus hydrochlorothiazide decreased the blood pressure of SHRSP to that of WKY, whereas the low-dose candesartan exerted no significant antihypertensive action. Media thickening and fibrosis, as well as the increased production of superoxide in SHRSP, were nearly normalized with high-dose candesartan and partially corrected with low-dose candesartan or hydralazine plus hydrochlorothiazide. These changes by antihypertensive treatment paralleled the decrease in mRNA expression of Nox4 and Nox1. These results suggest that blood pressure and angiotensin II type 1 receptor activation are involved in the up-regulation of Nox1 and Nox4 expression, which could contribute to vascular injury during chronic hypertension.     

Effect of allocating attention to aversive events on cardiovascular responses and event-related potentials in a dual-task paradigm.

This study investigated the effect of the allocation of attentional resources on event-related potentials (ERPs) and cardiovascular responses during a dual-task situation in which an avoidance task and a reward task were coupled. For the avoidance task, subjects were able to avoid an aversive shock that followed a target tone by pressing a button. For the reward task, subjects were asked to detect the direction of an arrowhead presented on the display screen and were rewarded for rapid, accurate reaction times. The 31 participants were divided into two groups based on their subjective impression of attention distribution between the avoidance and the reward task. Participants in the first group were motivated more by the avoidance task (AVD; n=18), whereas those in the second group were motivated more by the reward task (RWD; n=13). The ERPs to non-target and target tones, ECG, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were analyzed in the dual-task situation. The results indicated that the amplitudes of N1 to target and non-target tones, and of N2 to the target tone were larger in the avoidance (AVD) group than they were in the reward (RWD) group. The AVD group had higher blood pressure than did the RWD group during the aversive periods. However, there were no significant group differences in the mean RTs for avoidance and reward tasks, and participants in both groups reported similar subjective evaluations of their mental workloads. The results suggest a vigilant coping strategy that selectively focus attention to threatening information as illustrated by N1 and N2 changes may intensify psychophysiological arousal under stress.     

ENDOSCOPIC MANAGEMENT OF A DIEULAFOY‐LIKE LESION IN A DUODENAL DIVERTICULUM

We present a 70‐year‐old man who had two episodes of melena during the preceding 8‐year period. He had a Dieulafoy‐like lesion in a diverticulum in the third portion of the duodenum. While emergency endoscopy revealed neither apparent blood nor clots around the diverticular orifice, there was a non‐bleeding vessel in the fundus of the diverticulum. The vessel ceased bleeding after argon plasma coagulation and, since then, the patient has not experienced bleeding. In cases of gastrointestinal bleeding of obscure origin, duodenal diverticulum should be considered as a possible source of bleeding, even when endoscopy discloses no apparent bleeding.