CHARGE association with neuroblastoma

The CHARGE association, choanal arresia or coloboma with multiple anomalies, is rare. A newborn boy with CHARGE association was referred to our hospital because of bilateral choanal atresia. Additionally, he had left renal aplasia, one of the anomalies associated with this syndrome. A right suprarenal neuroblastoma (stage IV) was diagnosed when the patient was 5 months old. At operation, great care was taken not to injure the right kidney, and resection of the primary tumor as well as radical dissection of the right renal hilar and para-aortic lymph nodes were performed without difficulty. The patient received postoperative chemotherapy with vincristine, cyclophosphamide, and adriamycin for 2 years and is alive without recurrence 5 years after the operation. No report of the CHARGE association with a malignancy has appeared in the literature. The relationship between the CHARGE association and malignant tumors is still obscure, so that further study is necessary to define it.     

Clinical reevaluation of continuous intravenous infusion of 5-fluorouracil--plasma concentrations and clinical dose by continuous intravenous and 60-min infusions

Daily and intermittent continuous intravenous infusions [by gravity drip, (IVG) or infusion pump, (IVP)] and intermittent short-time intravenous drip infusion of 5-FU were carried out on advanced cancer patients. The MTD and dose-limiting toxicity were investigated in relation to the plasma concentrations of 5-FU determined by HPLC. Responses in eleven patients receiving IVG administration daily at 8-21 mg/kg/day were NC, but those given 5-FU alone showed no adverse reactions. Plasma concentrations were too low to be determined. In 9 patients receiving IVG or IVP administration weekly at 60 mg/kg for 24 hr, 1 of the 5 evaluable patients showed reduced hepatic metastatic lesions. One of 4 patients receiving IVP administration weekly at 120 mg/kg for 48 hr showed a disappearance of metastatic lesions in the skeletal muscle, but bone marrow suppression was observed as dose-limiting toxicity. Pharmacokinetics were more stable in IVP than in IVG with less individual difference in the plasma concentrations. Among the outpatients receiving short-time iv, IVG administration once or twice a week, 2 patients given weekly administrations at 20 mg/kg for 60 min showed slight adverse reactions. In 6 patients given high-dose administrations, bone marrow suppression was observed. When pharmacokinetics in the patients given 5-FU for 60 min were compared between the IVG and IVP groups, there were individual differences in plasma concentrations, but the differences were not significant. It was concluded from above results that the following practical dose schedules would be recommendable: 60 mg/kg for 24hr/week by IVP for inpatients and 20 mg/kg for 60 min/week by IVG for outpatients.     

Down-regulation of central serotonin S2 receptors after repeated treatment with quinupramine in rats

The present studies were undertaken to determine whether the repeated administration of quinupramine caused down- or up-regulation of beta-, alpha 2-adrenergic, serotonin S2, imipramine and muscarinic cholinergic receptors, as had been demonstrated for tricyclic and atypical antidepressant drugs. Quinupramine administered at 10 mg/kg (p.o.) twice daily for 10 days caused a down-regulation of serotonin S2 receptors in the frontal cortex of the rat as determined by [3H]ketanserin binding. However, quinupramine did not alter the binding populations of beta-adrenergic, muscarinic cholinergic and alpha 2-adrenergic receptors in the rat brain as determined by the Scatchard analysis of the [3H]ligand binding data. Differing from quinupramine, imipramine caused down-regulation of beta-adrenergic and serotonin S2 receptor bindings, and it caused slight but significant up-regulation of muscarinic cholinergic receptor bindings. These results show that the antidepressant activity of quinupramine is associated with the central serotonin system, but not with the beta-adrenergic system. Accordingly, quinupramine, chemically one of the typical tricyclic antidepressant drugs, seems to be pharmacologically one of the atypical antidepressant drugs, and it was suggested that the central serotonin system plays an important role in the antidepressant activity of quinupramine.     

Impact of smoking on the concentration and activity of alpha-1-antitrypsin in serum in relation to the urinary excretion of hydroxyproline

The impact of active and passive smoking on the serum levels of alpha 1-AT, the trypsin inhibitory capacity (TIC), the trypsin inhibitory activity (TIA) and the urinary hydroxyproline to creatinine ratio (HOP-ratio) was studied. The subjects used in the study on active smoking were 167 healthy adult men and in the study on passive smoking 189 healthy primary school children. Serum levels of alpha 1-AT in active smokers were significantly higher than those in non-smokers. The TIC as well as the TIA in active smokers decreased with increasing number of cigarettes smoked. The urinary HOP-ratio increased significantly with increasing number of cigarettes smoked. On the other hand, in the case of passive smokers a significant difference was obtained only for the HOP-ratio. The correlations between all markers in active smokers were significant. Less significant correlations were found in the case of passive smokers. These results suggest that the urinary excretion of hydroxyproline can be considered as a marker for the imbalance between proteases and anti-proteases as a result of smoking.     

Arterial and venous thrombus imaging using Ga-67 DFO-DAS-fibrinogen: its clinical applicability

The purpose of this study was the clinical application of 67Ga-DFO-DAS-fibrinogen 67Ga-fibrinogen in normal volunteers and patients with arterial or venous therombus, or bypass graft. DFO-DAS-fibrinogen was available as a lyophilized product and easily labeled by simple mixing with 67Ga-fibrinogen solution (2 mCi/2 ml). Images were taken by a scintillation camera 72 hours after the venous injection of 67Ga-fibrinogen (2 mCi). Ga-67 fibrinogen accumulated well in the liver and kidney in normal volunteers at the early stage, and radioactivity in the kidney, lung, and heart decreased after noticeably after 48 hours postinjection. Ga-67 fibrinogen clearly visualized fresh and old arterial thrombi localized in the thorax or abdomen of all patients suffering aneurysm, and in occlusive bypass graft, contrary to past observations with labeled fibrinogen. In venous thrombus, with the pulmonary artery included, visualization was limited to fresh thrombi of up to one month old. No adverse side effects were observed in any case.     

Pediatric liver transplantation from neonatal donors

Sixteen recipients of neonatal liver grafts were compared with 114 contemporaneous pediatric recipients of grafts from older donors. Graft and patient survival were worse in the neonatal group although the differences were not statistically significant. Patients with neonatal livers who had no technical complications required a longer time postoperatively to correct jaundice and a prolonged prothrombin time. These functional differences were limited to the 1st postoperative month and the end result was the same as with liver transplantation from older donors.     

Merkel cell carcinoma co-existent with sebaceous carcinoma of the eyelid

Merkel cell carcinoma is occasionally associated with other types of cutaneous malignancies including squamous cell carcinoma, basal cell carcinoma and lentigo maligna. We report a case of Merkel cell carcinoma co-existent with sebaceous carcinoma in the right upper eyelid of a 61-year-old Japanese man. Histopathologically, the resected tumor consisted of three nodules located in the tarsal plate, showing two distinct histopathological types. Two nodules were Merkel cell carcinoma and located in the proximal part of the palpebral conjunctiva. The third was sebaceous carcinoma located in the distal transitional zone between the epidermis and the conjunctiva. No features of transition between these two components were noted. Metastatic deposits were identified in the regional lymph nodes, which solely consisted of Merkel cell carcinoma without sebaceous carcinoma. This is the first report of such co-existent lesions.     

Overexpression of endothelial nitric oxide synthase attenuates cardiac hypertrophy induced by chronic isoproterenol infusion.

Endogenous nitric oxide (NO) inhibits the contractile response to beta-adrenergic stimulation, but its effect on cardiac hypertrophy mediated by beta-adrenoceptors remains unclear. The present study was designed to determine whether overproduction of endothelial NO synthase (eNOS) could inhibit cardiac hypertrophy induced by chronic isoproterenol (ISO) infusion (30mg/kg per day) using eNOS overexpressing (eNOS-Tg) mice and wild-type (WT) mice. In a separate group, WT mice were treated with ISO and hydralazine to decrease blood pressure to the same levels in eNOS-Tg mice. The eNOS expression, NOS activity, and cGMP levels in the heart were remarkably higher in eNOS-Tg mice than in WT mice. ISO increased both heart weight and the heart/body weight ratio, which were significantly attenuated in eNOS-Tg mice compared with WT or hydralazine-treated WT mice. Histological examination revealed that the extent of fibrosis was not significantly different among the 3 groups, and that the increase in myocyte size was more than 10% lower in eNOS-Tg than in the other groups. In addition, up-regulated expression of atrial natriuretic peptide mRNA associated with cardiac hypertrophy was significantly inhibited in eNOS-Tg mice during ISO infusion. These results indicate that endogenous NO might act as a negative modulator for the hypertrophic response to beta-adrenergic stimulation.