A comprehensive search for mutations in the PKD1 and PKD2 in Japanese subjects with autosomal dominant polycystic kidney disease.

To elucidate the genotypic and phenotypic characteristics of autosomal dominant polycystic kidney disease (ADPKD) in Japanese populations, we performed a comprehensive search for mutations in PKD1 and PKD2 in 180 Japanese ADPKD patients from 161 unrelated families. We identified 112 (89 PKD1 and 23 PKD2) mutations within 135 families. Patients with PKD2 mutations account for 23.6% of all Japanese ADPKD families in this study. Seventy-five out of the 112 mutations have not been reported previously. The estimated glomerular filtration rate (eGFR) decline was significantly faster in patients with PKD1 mutations than in those with PKD2 mutations (-3.25 and -2.08 ml min(-1) year(-1) for PKD1 and PKD2, respectively, p < 0.01). These results indicate that mutations within PKD1 and PKD2 can be linked to most of the cases of Japanese ADPKD, and the renal function decline was faster in patients with PKD1 mutations than in those with PKD2 mutations also in the Japanese ADPKD. We also found that PKD2 mutations were more frequent in Japanese ADPKD than that in European or American ADPKD.

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.

[The treatment of thymoma with myasthenia gravis: report of 20 cases].

Sixty-eight patients with myasthenia gravis underwent thymic surgery in our department. Among of 68 cases, twenty patients with thymoma were followed and their prognosis were investigated. Sixteen cases received a extended thymectomy with thymomectomy, six cases received local irradiation, and 16 cases received a chemotherapy. Among of 16 cases, 13 cases received corticosteroid only, and 3 cases received CHOP (CPA+ADM+VCR+PSL). Survival rates for thymoma of 20 cases were 94.7%, 88.9%, 78.6%, and 54.5% at 1, 3, 5 and 7 years, respectively. Survival rates for thymoma at 5 years were 83.3%, 50.0%, 100%, and 100% in stage I (complete encapsulation of 8), II (invasion into pericapsular fatty tissue of 7), III (invasion into surrounding organ of 3), and IV a (pleural dissemination of 2), respectively. Survival rate for extended thymectomy with thymomectomy of 16 cases was 81.8% at 5 years. Among of 18 total resection cases of thymoma, a recurrence occurred (5.6%). Causes of 6 death after surgery were crises of myasthenia gravis (3), other diseases (2), and recurrence of thymoma (1).

[Distribution of thymic tissue in the mediastinal adipose tissue removed at the thymectomy in 47 patients with myasthenia gravis].

In this report, the distribution of thymic tissue in the mediastinal adipose tissue was examined histologically in 54 patients with myasthenia gravis underwent extended thymectomy. In fourty-seven of 54 patients, the mediastinal adipose tissues were removed from 6 different parts adjacent to the thymus, i.e., right upper, right middle, right lower, left upper, left middle, and left lower, respectively. Upper area means of around the upper pole of thymus, middle area means of around hilum and lower area means of around from lower pole of thymus to diaphragma. In the mediastinal adipose tissue, thymic tissue was found outside the thymus lobes in 41 (75.9%) of 54 patients. The each prevalence (percent of occurrence) of 6 areas were as follows: 15.0% in the right upper area, 21.4% in the right middle area, 19.0% in the right lower area, 17.5% in the left upper area, 66.7% in the left middle area and 33.3% in the left lower area. There was significant differences in the prevalence of the left middle area according to the other 5 areas (p < 0.01). There were no significant differences in the prevalences among sex, Osserman type, duration of the disease, pre-operative treatment and histological findings or removal thymus. There were significant differences in the prevalence of all according to the proportion of thymic tissue in the thymus (0.01 < P < 0.05). In conclusion, it is suggested that for the removal of all thymic tissue, the sufficient procedure required utmost care especially to the left middle area around thymus.(ABSTRACT TRUNCATED AT 250 WORDS)

[The prediction of the need for postoperative mechanical ventilation in patients with myasthenia gravis undergoing transsternal thymectomy].

During a sixteen-year period, 51 patients with myasthenia gravis underwent trans-sternal thymectomy including extended resection of the adipose tissue around thymus. Using the criteria of risk factors described by Leventhal and Kimura, a predictive score was assessed for our 51 patients. Leventhal's scoring system achieved an accuracy of 54.3%, a sensitivity of 20.0% and a specificity of 63.9%. And, Kimura's scoring system achieved an accuracy of 75.0%, a sensitivity of 81.8% and a specificity of 73.0%. From this study it was concluded that Kimura's scoring system is statistically more adaptive for Japanese than Leventhal's scoring system, and the Leventhal's accuracy may have increased by adding "bulbar symptoms" and "preoperative crisis" as other risk factors and by decreasing "points" for "duration of myasthenia" and "pyridoxamine dosage", and the "Kimura's " accuracy may have increased by decreasing "7 points" for preoperative crisis. Consequently, patients who received postoperative ventilation were compared with the group who did not, with respect to the 19 factors. Evidence is that Osserman's type, bulbar symptoms, preoperative crisis and preoperative % VC were influenced to require the postoperative ventilation, but sex, age, thymic histology, duration of myasthenia and pyridoxamine dosage were not any influenced to require the postoperative ventilation.

[Effect of thymectomy in myasthenia gravis].

In order to examine the long-term effects of sternal splitting extended thymectomy in myasthenia gravis 42 patients were evaluated on an annual basis, beginning 12 months after surgery. The effects of surgery on the patients' myasthenic symptoms were as follows: 21.4% of the patients achieved complete remission, 61.9% showed improvement; in total 83.3% had palliation. There were no significant correlation among age, sex, Osserman type, pre-operative treatment and histological findings. Patients with long duration of the disease showed a statistically lower percentage of remission; the patients with complication after operation showed a lower percentage of palliation. The annual transition of the remission rate and the palliation rate were as follows: 11.8% of patients were in remission at 12 months after surgery; 16.1% at 24 months; and 17.4% at 36 months. Moreover 91.2% of the patients were palliated at 12 months after surgery; 90.3% at 24 months; 87.0% at 36 months; and 83.3% at 48 months. There was no significant difference in annual transition rates by age, Osserman type, pre-operative treatment and histology by scattering matric analysis. There was significant differences in annual transition rates according to dyspnea, duration of the disease, sex and post-operative complication.

Inhibition of oxidative injury of biological membranes by astaxanthin.

The value of astaxanthin, a carotenoid pigment, in the treatment of oxidative injury is assessed. Astaxanthin protects the mitochondria of vitamin E-deficient rats from damage by Fe2(+)-catalyzed lipid peroxidation both in vivo and in vitro. The inhibitory effect of astaxanthin on mitochondrial lipid peroxidation is stronger than that of alpha-tocopherol. Thin layer chromatographic analysis shows that the change in phospholipid components of erythrocytes from vitamin E-deficient rats induced by Fe2+ and Fe3(+)-xanthine/xanthine oxidase system was significantly suppressed by astaxanthin. Carrageenan-induced inflammation of the paw is also significantly inhibited by administration of astaxanthin. These data indicate that astaxanthin functions as a potent antioxidant both in vivo and in vitro.