Molecular forms of plasma and urinary adrenomedullin in normal, essential hypertension and chronic renal failure.

OBJECTIVES: Human adrenomedullin precursor is converted to glycine-extended adrenomedullin (AM-Gly), an intermediate inactive form of adrenomedullin. Subsequently, AM-Gly is converted to active form of mature adrenomedullin (AM-m). The aim of the present study was to investigate (i) whether sex or age influences plasma and urinary AM-m and AM-Gly levels in normal subjects; (ii) the daytime variability of plasma AM-m and AM-Gly levels in normal subjects; (iii) AM-m and AM-Gly levels and its ratio in plasma and urine in normal subjects, individuals with essential hypertension (HT), and chronic renal failure (CRF); and (iv) the ratio of AM-m and AM-total (T) in plasma of various veins and aorta. METHODS: We measured plasma levels and urinary excretions of AM-m, AM-Gly and AM-T (AM-m + AM-Gly) by recently developed immunoradiometric assay in normal subjects (n = 81), HT (n = 28) and CRF (n = 30). We also determined the molecular forms of plasma adrenomedullin taken from various sites during angiography in patients with suspected renovascular hypertension (n = 9). RESULTS: There were no differences in plasma and urinary excretions of two molecular forms of adrenomedullin among sexes or ages in normal subjects. There was no daytime variation of plasma two molecular forms of adrenomedullin in normal subjects. Plasma AM-m, AM-Gly and AM-T levels were increased in patients with HT and CRF compared with normal subjects, whereas urinary AM-m, AM-Gly and AM-T excretions were decreased in patients with HT and CRF compared with normal subjects. Urinary AM-m: AM-T ratios were significantly higher than plasma AM-m: AM-T ratios. Plasma AM-m and AM-T levels taken from various veins were similar, and they were significantly higher than those of aorta, although there were no differences in plasma AM-Gly levels between aorta and veins. CONCLUSIONS: These results suggest that in normal subjects, and individuals with HT and CRF: (i) plasma and urinary excretions of AM-m and AM-Gly are not affected by age or sex; (ii) AM-m in parallel with AM-Gly is increased; (iii) urine contains a higher percentage of active adrenomedullin than plasma; and (iv) plasma AM-m may be partly metabolized in the lung.

Transcatheter arterial chemoembolization in the treatment of hepatoblastoma.

BACKGROUND: The prognosis of hepatoblastoma is poor unless the tumor is completely resected. Various types of chemotherapy have been developed to increase its resectability. Recently, transcatheter arterial chemoembolization (TACE) has been developed for the treatment of unresectable adult hepatoma with favorable results. The authors applied this procedure to hepatoblastoma in infants and children. METHODS: TACE was performed in eight hepatoblastoma cases. After an intraarterial catheter was inserted into the main feeding artery of the tumor, injection of adriamycin or THP-adriamycin (20 to 30 mg/m2) dispersed in lipiodol and cisplatin (40 to 60 mg/m2) followed by embolization using Gelfoam pieces was performed. Effects of TACE were evaluated according to shrinkage of tumor mass on imaging examinations, alpha-fetoprotein (AFP) levels, and pathological findings of the surgical specimens 4 weeks after TACE. RESULTS: A marked reduction in tumor size associated with a decrease in AFP level occurred 1 month after the treatment. Tumor shrinkage ranged from 0.9% to 45.0% with a mean value of 25.8%. AFP levels decreased by 0.2% to 11.9% with a mean level of 4.6% from initial levels. In addition, there was no marked chemotherapeutic agent-induced toxicity noted during the observation period. Resection of the tumors was performed safely after TACE in all cases. Pathological examination showed massive necrosis in the surgical specimens, and the mean percentage of necrotic area within the tumor was 71.1%. Two patients died of extensive lung metastasis 2 months and 3 years after the operation, respectively. The remaining six were doing well and free of disease at a mean follow-up period of 50 months. CONCLUSION: TACE is an effective, safe, and useful method for the initial treatment of hepatoblastoma.

Thirty-eight years experience of malignant hepatic tumors in infants and childhood.

A description is given of therapeutic experiences with 39 cases of malignant liver tumors in infancy and childhood during the past 38 years. Of these patients, 9 not undergoing hepatic resection all died, while 18 (60%) of 30 patients treated by hepatic resection survived. When only patients with hepatoblastoma are considered, 14 of 24 patients are alive, although 3 of them had local recurrence and had lung metastasis. Among patients with other types of liver tumor, those with hepatocellular carcinomas (2 cases) and vascular neoplasms all died in a short period of time, whereas 2 with yolk sac tumor and one with metabolic pancreatic tumor are alive despite of tumor recurrence. In summary, the results of surgical treatment of malignant liver tumors in infancy and childhood, which formerly were poor, have been improved remarkably, which we owe mainly to: 1) advances in diagnostic imaging techniques (e.g., angiography, ultrasonography, CT and MRI) permitting early diagnosis, localization of tumor, visualization of the coursing of major vessels (particularly, hepatic artery & vein) and more accurate definition of resectability, 2) technical improvement of hepatic resection and 3) progress of chemotherapy mainly with cisplatin and adriamycin.

In situ detection of DNA fragmentation and expression of bcl-2 in human neuroblastoma: relation to apoptosis and spontaneous regression.

UNLABELLED: Spontaneous regression occurs in some cases of neuroblastoma, especially stage IVS. The incidence of neuroblastoma has been reported to be increasing since the mass screening program was introduced in Japan. This would indicate that the screening is detecting regressing tumors. However, the mechanism of regression is still unknown. To evaluate the hypothesis that the regression might be related to apoptosis, the authors examined apoptosis by in situ end-labeling of fragmented DNA and expression of the apoptosis-suppressing protein bcl-2. MATERIALS AND METHODS: One hundred eighteen neuroblastoma cases were available for examination. Eighty (67.8%) were detected by the mass screening program. Serial sections were cut from paraffin-embedded tumors. A modified TdT-mediated dUTP nick end-labeling (TUNEL) method was performed to detect apoptosis. Immunohistochemical analysis was performed to detect bcl-2 expression. RESULTS: In cases under 1 year of age or with a favorable clinical stage, the incidence of apoptosis was significantly high. Expression of bcl-2 was associated with N-myc amplification and unfavorable histology (Shimada classification). Tumors in patients under 1 year of age often had areas where cellularity was markedly decreased, and apoptosis was often observed while bcl-2 expression was reduced. In such cases, there was a negative correlation between occurrence of apoptosis and bcl-2 expression. This suggests that apoptosis may be related to spontaneous regression in neuroblastoma.

[A study on ceftriaxone in the perinatal period].

Ceftriaxone (CTRX), a new cephem antibiotic with high activity against Gram-positive and Gram-negative bacteria, was investigated pharmacokinetically in 30 mothers in the perinatal period. The obtained results are summarized below. 1. The maximum CTRX level in the maternal serum was 135 micrograms/ml between 20 and 25 minutes after an intravenous administration of 1 g of CTRX. 2. The transfer of CTRX into the umbilical cord serum and the amniotic fluid was very good. CTRX levels in these fluids were about 20% and 10% of the maternal serum level, respectively. 3. No side effect was observed in mothers or neonates. 4. CTRX is a useful antibiotic for perinatal infections.

[Fundamental and clinical studies on latamoxef in the perinatal period].

Fundamental and clinical studies on latamoxef (LMOX) in the perinatal period were carried out, and following results were obtained. Concentration of LMOX was showed high peak levels in maternal serum, umbilical serum and amniotic fluid. LMOX seemed to be a very transferable compound to human tissues. LMOX was administered to 28 cases of various perinatal infections. Clinical responses were excellent in 13 cases, good in 15 cases and poor in none. And 140 cases of prophylactic use in the field of perinatal period were evaluated in good. No side effect was seen and an abnormal laboratory finding, the increase of GPT, was observed in only 1 case. LMOX was a highly useful antibiotic in perinatal infections, the safe dose range of LMOX into the perinatal mothers was estimated to be 2 g/day, with the maximum safe dose being 4 g/day.