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We report an unusual case of malignant mixed mesodermal tumor of the uterine corpus associated with various symptoms related to overproduction of catecholamine by the tumor cells. Histologically, the tumor was dominated by carcinomatous epithelium with foci of malignant mesenchyma. The type of epithelium was endometrioid with papillary adenocarcinomas containing foci of malignant squamous epithelium. The malignant mesenchyma consisted mainly of a fibrous stroma with many large and bizarre cells and spindle cells mimicking leiomyosarcoma, many of which were pleomorphic and contained large bizarre hyperchromatic nuclei. Foci of atypical adult-type cartilage and neoplastic osteoid formation were noted. In the tumor tissue, membrane-bound neurosecretory-type cytoplasmic granules were demonstrated by electron microscopy and polypeptide hormone synthesis was demonstrated by immunohistochemistry. Furthermore, the patient suffered frequent attacks of sudden hypertension with hypercatecholaminemia.

A multicenter, open-label trial in Japan examined the efficacy, safety, and optimal dose of monatepil (AJ-2615) as monotherapy and in combination therapy with angiotensin-converting enzyme (ACE) inhibitors or beta-blockers. Patients with essential hypertension who had never been treated or had been refractory to conventional antihypertensive agents were enrolled in the trial. During a 4-week control period patients assigned to monotherapy received placebo and those assigned to combination therapy received an ACE inhibitor or beta-blocker and placebo. Patients with systolic blood pressure (BP)or = 160 mm Hg and diastolic BPor = 95 mm Hg at the end of the control period were enrolled in the study. The initial dose of monatepil was 30 mg/day in monotherapy and 15 mg/day in combination therapy; the daily dose was titrated to 60 mg/day according to the antihypertensive response. The treatment period was 8 to 12 weeks. Blood pressure decreased from 168 +/- 8/100 +/- 6 to 142 +/- 9/85 +/- 7 mm Hg (SD) with monatepil monotherapy, from 171 +/- 11/102 +/- 6 to 141 +/- 9/84 +/- 6 mm Hg in combination with ACE inhibitors, and from 175 +/- 13/102 +/- 7 to 153 +/- 21/91 +/- 9 mm Hg in combination with beta-blockers (P.001). When patients in whom mean BP decreased byor = 13 mm Hg were defined as responders, the response rate was 80.4%, 78.1%, and 51.6% in the respective groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary immunoreactive endogenous digitalis-like substance (EDLS) excretion was studied in gradually reduced renal mass rats (RRM). Urinary EDLS increased immediately after the start of 1% NaCl ingestion, then it returned to the basal level 2 weeks later. Both urinary sodium excretion and urinary EDLS were significantly higher in 3/6 and 4/6 RRM than in control until 2 weeks after starting 1% NaCl. However, there was no difference in blood pressure between the groups. Transient EDLS increase may play an important role in maintaining sodium and water homeostasis, but its transient increase apparently does not contribute to blood pressure elevation.

In order to evaluate the usefulness of urapidil in the treatment of severe hypertension and in the long-term treatment of essential hypertension, two open multicentre studies were performed. In one study, 34 outpatients with diastolic blood pressure exceeding 105 mmHg following treatment with a combination of a diuretic and a sympatholytic or a diuretic and a beta-blocker were additionally given 15-60 mg urapidil twice a day for 8 weeks or more. The responder rate was 73.5%. The pulse rate did not change throughout. Side effects such as dizziness and malaise were observed in five patients (14.7%), but they were slight and did not require withdrawal of treatment. The other study included 95 outpatients with essential hypertension (World Health Organization stages I or II), 15-60 mg urapidil twice a day for 1 year or more in monotherapy (n = 48) or in combined therapy with a thiazide (n = 47). Under both therapies, diastolic blood pressure was reduced significantly at week 4, further reduced at week 12 and remained stable until week 52. Responder rates were 82.9% in monotherapy and 78.4% in combined therapy. Two patients (4.2%) taking monotherapy and six patients (12.8%) taking combined therapy were withdrawn due to inadequate blood pressure control or to side effects. These results indicate that urapidil is useful in severe and in long-term hypertension.