Effects of up-titration of candesartan versus candesartan plus amlodipine on kidney function in type 2 diabetic patients with albuminuria.

In the present study, we tested the hypothesis that up-titrating the dose of an angiotensin receptor blocker (ARB) is superior to combined treatment with an ARB and a calcium channel blocker for the same degree of blood pressure (BP) reduction, with respect to urinary albumin excretion in diabetic patients treated with a standard dose of the ARB. Hypertensive patients with type 2 diabetes mellitus and albuminuria (≥30 mg g(-1) creatinine) were enroled in the study, and were either started on or switched to candesartan (8 mg per day) monotherapy. After a 12-week run-in period, baseline evaluations were performed and patients with BP ≥130/80 mm Hg were randomly assigned to receive either candesartan (12 mg per day) or candesartan (8 mg per day) plus amlodipine (2.5 mg per day) for a further 12 weeks. The primary end-point was a reduction in urinary albumin levels. Although there was no significant difference in the BP reduction between the two groups, the reduction in urinary albumin was greater in the up-titrated than the combination therapy group (-40±14% vs -9±38%, respectively; P<0.0001). Thus, up-titration of candesartan more effectively reduces urinary albumin excretion than combined candesartan plus amlodipine in hypertensive patients with diabetes for the same degree of BP reduction.

Atopic dermatitis as a risk factor for acute native valve endocarditis.

Colonization of Staphylococcus aureus is commonly observed in skin lesions of atopic dermatitis (AD) patients, and scratching of the pruritic lesions may lead to reiterative bacteremia. It is possible that acute native valve endocarditis may develop in a patient with uncontrolled AD; the latter condition may be a risk factor for the former. We report two cases of acute aortic and/or mitral valve endocarditis complicated with recurrent cutaneous infections caused by severe AD. The patients underwent successful surgical treatment of the heart lesions, plus intensive postoperative antibiotics and skin treatment for AD.

[The effects of intravenous milrinone for the patient undergoing CABG].

The hemodynamic effects of intravenous infusion of milrinone were evaluated in 25 patients undergoing CABG using an internal mammary artery graft. Milrinone was administered to 9 patients at the time of weaning from cardiopulmonary bypass, at a dosage of 3 to 5 micrograms/kg/min. Postoperative cardiac function was compared in this group versus the other 17 patients who were treated without milrinone. We determined such parameters as cardiac index, wedge pressure and mean pulmonary pressure. Our findings did not show any significant difference between the 2 groups. We also studied a subject of low-output patients (EF < 0.5). In the patients with low-cardiac output, the use of milrinone in addition to standard postoperative administration of low-dose dopamine reduced mean pulmonary pressure and wedge pressure. Thus, milrinone not only improved the left ventricular function, but also expanded the pulmonary vascular bed.

Five-year follow-up of valve replacement with the Jyros bileaflet mechanical valve.

Jyros bileaflet rotating valves were implanted as a clinical trial conducted in Japan, and the 5-year results were assessed. Nineteen patients underwent implantation of the valves: 14 in the mitral and 5 in the aortic position. The mean follow-up period was 65.4+/-15.7 months. There was 1 case of late death due to fatal arrhythmia and another case of cerebral thromboembolism (1.0% per patient year). All survivors were in New York Heart Association class I. On the early postoperative cinefluorography, 8 valves (42.1%) showed rotation of the leaflets. However, in the latest assessment 6 valves (33.3%) showed rotation, some valves had stopped rotation, and others had started to rotate during the follow-up period. The Jyros valve functions effectively, similar to other bileaflet valves. However, because the correlation between thromboembolism and the rotation mechanism is not clear, further follow-up of our patients and more implant studies are necessary to elucidate this issue.

Novel specific chemtactic receptor for S100L protein on guinea pig eosinophils.

We isolated a new chemotactic protein from bovine lung, and its partial protein sequence analysis indicated that this protein was identical with S100L, one member of the Ca2+-binding S100 protein family. The chemotactic activity of S100L on guinea pig eosinophils is observed at 0.1nM protein concentration, and the effects appear mediated by a novel specific surface receptor. We characterized the receptor for S100L on guinea pig eosinophils. Scatchard analyses of the data that [125I]S100L bound to S100L receptor indicate the presence of two receptor populations on eosinophils with a Kd value of 3.3 x 10(-11)M and 1.1 x 10(-9)M. Thus, S100L protein has the most potent chemotactic activity on guinea pig eosinophils of all the chemotactic proteins.

Immunological study of anti-M2 in antimitochondrial antibody-negative primary biliary cirrhosis.

We investigated the specificity of various autoantibodies in antimitochondrial antibody (AMA)-negative patients with primary biliary cirrhosis (PBC). We examined sera from 144 patients with PBC, 17 of whom were AMA negative by indirect immunofluorescence. The AMA-negative group showed a significantly higher positivity for smooth muscle antibody, but not for antinuclear antibody, as compared with the AMA-positive group. IgG class anti-PDH by enzyme-linked immunosorbent assay (ELISA) were detected in 13% of the AMA-negative group. However, all PBC patients showed positive IgG, IgA, and/or IgM class anti-M2 to the four M2 proteins by immunoblotting. These results suggest that the detection of IgG and IgM class anti-PDH and that of antibodies to the four M2 proteins increases the positivity of this ELISA method, and that detection of IgG, IgA, and IgM class anti-M2 to the four M2 proteins by immunoblotting is useful in diagnosing AMA-negative patients with PBC.

Protein kinase C-independent activation of Raf-1 and mitogen-activated protein kinase by leukotriene B4 in guinea pig eosinophils.

Leukotriene B4 (LTB4) and phorbol 12-myristate 13-acetate (PMA) were found to activate serine/threonine kinase c-Raf-1 (Raf-1) and mitogen-activated protein (MAP) kinase in guinea pig eosinophils. Raf-1 was activated by both compounds in a time- and dose-dependent fashion, and the activation by each paralleled that of MAP kinase. The LTB4 receptor antagonist ONO-4057 prevented the LTB4-induced activation of Raf-1 and MAP kinase, but had no effect on the PMA-induced activation of these kinases. The protein kinase C (PKC) inhibitors, (+/-)1-O-hexadecyl-2-O-methylglycerol (AMG-C16) and bisindolylmaleimide (GF 109203X), suppressed the PMA-induced activation of Raf-1 and MAP kinase, but not the LTB4-induced activation of both kinases. Our findings suggest that the activation of Raf-1 and MAP kinase by LTB4 involves a PKC-independent pathway.

Clinical experience with Nikkiso centrifugal pumps for extracorporeal circulation.

A comparative study of a newly developed impeller-type centrifugal pump, Nikkiso HMS-15, was made to assess the effects on hemolysis, platelet function, and renal function for extracorporeal circulation (ECC) during open heart surgery. The Bio-pump (cone-type, Medtronic) and the roller pump were used as controls. The increase of serum hemoglobin level in the Nikkiso pump was significantly lower than that in the other pumps. The decrease of platelet counts was recognized after the initiation of ECC in the three pumps whereas the levels of platelet factor 4 and beta-thromboglobulin in the Nikkiso pump group increased by far less than in the other two groups. Moreover, renal function was better maintained in the Nikkiso pump group; in particular, a significantly higher urine output was recorded during ECC and for 1 h after the termination of ECC. The results of our clinical studies suggest that the Nikkiso centrifugal pump is suitable for ECC during open heart surgery.

Immunoreactivity to M2 proteins in antimitochondrial antibody-negative patients with primary biliary cirrhosis.

Although antimitochondrial auto-antibodies are characteristically present in the serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy between the positivity for antimitochondrial antibody (AMA) and that for anti-M2 auto-antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreactivity to four inner mitochondrial membrane proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There were no significant differences between the AMA-negative and AMA-positive groups in clinical characteristics or histologically determined disease stage. Immunoblot analysis showed that all patients had anti-M2 auto-antibodies to one or more of the four M2 proteins. Nine (60%) of the 15 AMA-negative patients had antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres (> or = 1:320) had antibodies to all four M2 proteins. There was a significant rank correlation between the AMA titre and the number of antibodies to M2 proteins (P < 0.01). These findings indicate that the AMA titre is not influenced by the immunogenicity of M2 proteins but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.

Protective effect of DS-4574 on gastric mucosal injury induced by acidified ethanol in rats.

We compared the protective effect of DS-4574, a peptidoleukotriene receptor antagonist with mast cell stabilizing action, on rat gastric mucosal injury induced by acidified ethanol to that of LY171883, a selective peptidoleukotriene receptor antagonist. Oral treatment with DS-4574 (1-10 mg/kg) or LY171883 (100 and 300 mg/kg) markedly suppressed this mucosal necrosis. Moreover, DS-4574 (10 mg/kg) significantly inhibited both mucosal edema and degranulation of mucosal mast cells. LY171883 (300 mg/kg) protected only from mucosal edema, but not degranulation of mucosal mast cells. These results suggest that DS-4574 possesses protective actions against gastric injury including the reduction of degranulation of mucosal mast cells, which are different from those of LY171883.

[Left atrial myxomas: clinical characteristics, evaluation and considerations in classifying tumors].

Eleven patients underwent surgical excision for left atrial myxomas. Clinical symptoms, coronary angiographic findings and operative procedures were evaluated. Myxomas were classified into two types based on macroscopical findings, and clinical characteristics of these two types were analyzed. Seven cases (64%) classified as "lobular-type myxomas" were seen as lobulated, gelatinous and fragile. Four cases (36%) were classified as "round-type myxomas" were round and elastic soft. Primary symptoms included dyspnea on exertion in five cases (45%) and neurological disturbances in six cases (55%). Brain emboli were found in four patients by CT scan, and were classified as lobular-type myxomas. These eleven myxomas successfully removed in all cases. Four of these myxomas, which were pedunculated with fine fibrous stalks, were shaved along the base at the atrial septum or free wall. Others were excised completely along with a portion of the adjacent septum. Microscopic examination of the operative specimens revealed that two lobular-type myxomas with broad-based attachment to left atrial septum had invaded the atrial septum. All patients are doing well and have had no signs of myxoma recurrence at postoperative periods ranging from 10 months to 12 years (mean follow-up 5.3 years). Seven patients underwent selective coronary angiography due to a diagnosis of a coronary artery disease. All coronary angiograms were normal in all cases. In five (71%) of these seven, abnormally dilated atrial branches were seen as supplying the tumor. In two cases with round-type myxomas, neovascularity was evident and was made up of clusters of tortuous vessels with tumor blush.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a protein-bound polysaccharide from a basidiomycetes against hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene in rats.

PSK, extracted from mycelia of a strain of Coriolus versicolor, was administered to groups of 20 male Wistar rats before and during treatment with 3'-methyl-4-dimethylaminoazobenzene (3-MDAB). After 24 weeks, the survival rates were significantly higher in the groups given PSK before or with the 3-MDAB than in groups not given PSK or given PSK after 12 weeks of 3-MDAB treatment. Blood alpha-fetoprotein levels, determined every four weeks, increased in all groups after 3-MDAB treatment, but were significantly lower in the groups given PSK before or with the 3-MDAB than in the other groups. The results indicate that PSK had a suppressive effect on 3-MDAB-induced hepatocarcinogenesis.

Simple method for reconstruction of the cleft hand with an adducted thumb.

We describe a new, simple method for reconstruction of a cleft hand. Ulnar transposition of the index ray followed by creation of a thumb web space is an effective way to get sufficient abduction of the thumb. This procedure is simpler than the traditional "translocation of the flap," and also it produces no circulatory troubles to worry about.

Anterior interosseous nerve paralysis: report of 13 cases and review of Japanese literatures.

Fifty-six cases of anterior interosseous nerve paralysis including our thirteen cases were collected by reviewing the Japanese literature. The causes of the paralysis were similar to those in the cases reported in other countries. Paralysis is often only partial, and this is of importance in the differential diagnosis.