Antihypertensive effect of a fixed-dose combination of losartan/hydrochlorothiazide in patients with uncontrolled hypertension: a multicenter study.

BACKGROUND: Achieving adequate blood pressure (BP) control often requires more than one antihypertensive agent. The purpose of this study was to determine whether a fixed-dose formulation of losartan (LOS) plus hydrochlorothiazide (HCTZ) (LOS/HCTZ) is effective in achieving a greater BP lowering in patients with uncontrolled hypertension. METHODS: The study was a prospective, multicenter, observational trial exploring the antihypertensive effect of a single tablet of LOS 50 mg/HCTZ 12.5 mg. A total of 228 patients whose BP had previously been treated with more than one antihypertensive agents without having achieved BP goal below 130/80 mmHg enrolled in the study. RESULTS: A significant decrease in systolic and diastolic BP was observed in both clinic and home measurement after switching from the previous treatment to LOS/HCTZ. There was a significant decrease in both B-type natriuretic peptide (BNP) and urinary albumin creatinine (Cr) excretion ratio (ACR), especially in patients with elevated values. In contrast, there was a significant increase in serum Cr concentration in conjunction with a decrease in estimated glomerular filtration rate (eGFR). Overall serum uric acid (UA) concentration increased, whereas in patients with hyperuricemia there was a significant reduction in this value. CONCLUSION: Switching to LOS/HCTZ provides a greater reduction in clinic and home BP in patients with uncontrolled hypertension. This combination therapy may lead to cardio-, reno protection and improve UA metabolism.

Oestrogen receptor-alpha contributes to the regulation of the hedgehog signalling pathway in ERalpha-positive gastric cancer.

BACKGROUND: Oestrogen receptor-alpha (ERalpha) is highly expressed in diffuse-type gastric cancer and oestrogen increases the proliferation of ERalpha-positive gastric cancer. However, a detailed mechanism by which oestrogen increases the proliferation of these cells is still unclear. METHODS: We used 17-beta-oestradiol (E2) as a stimulator against the ERalpha pathway. Pure anti-oestrogen drug ICI 182 780 (ICI) and small interfering RNA against ERalpha (ERalpha siRNA) were used as inhibitors. Cyclopamine (Cyc) was used as the hedgehog (Hh) pathway inhibitor. Two human ERalpha-positive gastric cancer cells were used as target cells. Effects of the stimulator and inhibitor on E2-induced cell proliferation were also examined. RESULTS: In ERalpha-positive cells, E2 increased not only cell proliferation but also one of the ligands of the Hh pathway, Shh expression. 17-beta-Oestradiol-induced cell proliferation was suppressed by ICI, ERalpha siRNA or Cyc. The increased expression of Shh induced by E2 was suppressed by ICI and ERalpha siRNA but not by Cyc. Furthermore, recombinant Shh activated the Hh pathway and increased cell proliferation, whereas anti-Shh antibody suppressed E2-induced cell proliferation. When a relationship between ERalpha and Shh expressions was analysed using surgically resected gastric cancer specimens, a positive correlation was found, suggesting a linkage between the ERalpha and Hh pathways. CONCLUSION: Our data indicate that activation of the ERalpha pathway promotes cell proliferation by activating the Hh pathway in a ligand-dependent manner through Shh induction of ERalpha-positive gastric cancer.

Differences in receptor specificity between Newcastle disease viruses originating from chickens and waterfowl.

We compared the receptor specificity of Newcastle disease viruses from a variety of avian species, including chickens and wild waterfowl, using hemagglutination tests with erythrocytes from different animal species. All isolates from wild waterfowl agglutinated horse erythrocytes, while the chicken isolates did not. The results showed that the receptor specificity of Newcastle disease viruses is different, depending on the avian species from which the viruses are isolated.

Treatment of hypervascular small hepatocellular carcinoma with ultrasound-guided percutaneous acetic acid injection: comparison with segmental transcatheter arterial embolization.

OBJECTIVE: To compare the efficacy of ultrasound-guided percutaneous acetic acid injection and segmental transcatheter arterial embolization for hypervascular small hepatocellular carcinoma. METHODS: The prognosis of 40 patients with one to three angiographically hypervascular hepatocellular carcinoma smaller than 3 cm in diameter treated with either percutaneous acetic acid injection (25 patients) or transcatheter arterial embolization (15 patients) during the past 4.5 yr were analyzed retrospectively. RESULTS: After initial therapy, none of 25 patients treated with percutaneous acetic acid injection developed ascites, whereas 5 of 15 (33%) patients treated with transcatheter arterial embolization developed it (p < 0.01). All tumors became smaller once after each therapy. However, local recurrence (reenlargement of the original tumor) occurred in 1 of 29 (3%) tumors treated with percutaneous acetic acid injection and 11 of 22 (50%) tumors treated with transcatheter arterial embolization (p < 0.005). During the follow-up, 4 of 25 (16%) patients treated with percutaneous acetic acid injection and 10 of 15 (67%) patients treated with transcatheter arterial embolization died. The 1-, 2-, and 3-yr survival rate was 100, 94, and 83%, respectively, in patients treated with percutaneous acetic acid injection and 72, 65, and 39% in patients treated with transcatheter arterial embolization (p < 0.005). The cancer-free survival rate was also significantly better in the former than in the latter group (p < 0.005). CONCLUSIONS: Percutaneous acetic acid injection is superior to segmental transcatheter arterial embolization in the treatment of hypervascular small hepatocellular carcinoma.

99mTc-DTPA activity in the azygos vein before and after sclerotherapy in patients with cirrhosis.

We determined the radioactivity of 99mTc-diethylene-triamine pentaacetic acid (99mTc-DTPA) from the azygos vein in 20 patients with cirrhosis to evaluate the hemodynamic relationship between esophageal varices and azygos venous blood flow before and after sclerotherapy. 99mTc-DTPA was injected into the splenic artery before and after sclerotherapy through a catheter in the right femoral artery. The patients were classified into three types. Type I consisted of nine patients who showed maximum levels of 99mTc-DTPA which were significantly lower (P < 0.01) than those determined before sclerotherapy. The Type II was composed of six patients who had far lower radioactivity levels than those of Type I, but also showed significantly lower maximum activity after sclerotherapy than before (P < 0.01). The five patients in Type III had significantly higher radioactivity after sclerotherapy than before (P < 0.05). Rupture of the esophageal varices occurred in one of the Type I (11.1%), none of the Type II, and four of Type III (80%) cases, among all of the patients followed for 40 months after sclerotherapy. The radioactivity in the azygos vein appeared later in Type I (P < 0.05) and Type II after sclerotherapy than before sclerotherapy, but in Type III there was no difference between pre- and post-sclerotherapy values. Type III patients in whom portography was performed showed short gastric and paraesophageal veins, whereas Type I and Type II patients did not. These data suggest that radioactivity in the azygos vein before and after sclerotherapy reflect the grade of shunting and estimate the recurrence of bleeding in patients with cirrhosis associated with esophageal varices.

Changes in liver calcium content in relation to serum triiodothyronine (T3), thyroxine (T4) and T3/T4 ratio in rats treated with CCL4.

To evaluate the relation between liver calcium content and microsomal function in liver injury, we determined liver calcium content, serum triiodothyronine (T3), thyroxine (T4), T3/T4 ratio and serum glutamic pyruvic transaminase (SGPT) content in rats treated with CCl4. The T3/T4 ratio decreased from 1.9 to 1.2 at 6 hr after treatment, but elevated immediately to 3.2 at 36 hr after, and returned to normal at 54 hr after treatment. The calcium content increased from 27 micrograms/g wet weight to 448 micrograms/g wet weight 24 hr after treatment and decreased to normal 78 hr after treatment. The SGPT concentration showed the highest 12 hr after and returned to normal 72 hr after treatment. The calcium content was significantly correlated with T3 (r = -0.5, p less than 0.05). These results suggest that the increase and decrease in liver calcium content are closely related to the decrease and increase in T3 and T3/T4 ratio, respectively.

[Evaluation of tegafur encapsulated with slow-releasing granules (SF-SP) for patients with cancer of the digestive organs].

A new anticancer therapy using tegafur encapsulated in slow-releasing granules (SF-SP) was orally administered at a dose of 1000 mg/day to 38 patients with cancer of the digestive organs. Twenty-eight of these patients were evaluable for response using the criteria of Saito and Koyama's clinical evaluation. Six of 28 patients showed effective response (21.4%). An effective response was observed in of 15 patients with gastric cancer (26.7%). Side-effects from this therapy were encountered in 14 patients (36.8%). An effective response was therefore demonstrated in patients with cancer of the digestive organs.