Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant

Encouraging results are reported with high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem. We used high-dose chemotherapy, surgery, intraoperative radiation and an autologous bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis-retinoic acid to treat 36 children with advanced neuroblastoma. This comprehensive treatment appears to improve the survival rate of patients with advanced neuroblastoma, including those with N-myc amplification and bony involvement. The disease-free survival rate was 66% (95% confidence interval, 49–84%) at 3 years. All patients who received 13-cis-retinoic acid developed cheilitis, but no bone marrow depression occurred in these patients. Five patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have been related to the procedure used for total body irradiation. Patients who had their kidneys shielded during this procedure did not develop this syndrome. Patients who received local irradiation at the primary site showed no evidence of relapse in this region, indicating that such therapy may help to prevent a relapse. These data suggest a high rate of 3 year disease-free survival with this treatment strategy. The nonrandomized nature of the study and use of multiple modalities precludes analysis of the specific contribution of each.     

A Case of Hepatocellular Carcinoma Developed on Polycystic Disease of the Liver with Cirrhosis

A case of hepatocellular carcinoma associated with polycysticdisease of the liver and posthepatitic cirrhosis in a 56-year-oldKorean woman was described. She was first admitted because ofepigastralgia, irradiated back pain and general fatigue. Onthe liver scan a relative cold area was demonstrated. The celiacangiography revealed multiple avascular areas indicating cysticlesions. The exploratory laparotomy confirmed the presence ofpolycystic disease of the liver with cirrhosis. Four years afterthe first admission, she underwent an appendectomy. At the timeof operation, the surgeon suspected the presence of hepatocellularcarcinoma, and she was admitted for the second time to our hospital.The minimal elevation of serum -fetoprotein was observed. Thedevelopment of hepatocellular carcinoma was confirmed by theceliac angio graphy, and a partial lobectomy of the liver wasperformed. Four months after the operation she died of hepaticfailure. Of the four reported cases of hepatocellular carcinoma associatedwith polycystic disease of the liver including this case, allhad liver cirrhosis, and serum HBs-Ag was positive in all ofthe three cases examined.     

麦角新碱激发试验诊断变异型心绞痛

随着心血管疾病介入诊断技术的不断发展与普及,选择性冠状动脉造影已经成为冠心病诊断的“金标准”。但发作性痉挛所引起的变异型心绞痛仍是常规冠脉造影的“盲点”。笔者采用静脉注射麦角新碱激发冠状动脉痉挛的方法诊断变异型心绞痛,获得满意效果,现报告如下。1　资料与方法1.1　一般临床资料　主诉为发作性胸痛,临床疑诊为变异型心绞痛的患者12例,其中男7例,女5例,年龄48～69岁,全部病例均未捕捉到发作时ＳＴ段抬高的心电图,平时心电图亦无明显ＳＴ段上抬或下移。激发试验前选择性冠脉造影示无明显冠状动脉固定狭窄者9例,冠状动脉狭窄25%者3例(左前降支2例,右侧冠状动脉1例)(附表)。1.2　方法　麦角新碱激     

The Disposition of the Tolcapone 3-O-Methylated Metabolite is Affected by the Route of Administration in Rats

Abstract— Catechol-O-methyltransferase (COMT) catalyses the transfer of the methyl group from S-adenyl-l -methionine (SAM) to one of the hydroxy groups of a catechol, usually the hydroxy group in position 3. COMT is present mainly in a soluble form (S-COMT) in the cytosol, but a small fraction is bound to cell membranes (MB-COMT). MB-COMT has higher affinity for the catechol substrate than does S-COMT by a factor of > 10, and high MB-COMT activity is observed in the intestinal muscle layer. The present study investigates the effect of the administration route on the disposition of the tolcapone 3-O-methylated metabolite following intravenous and oral tolcapone administration in rats. Tolcapone is a substrate for COMT although the 3-O-methylated metabolite produced has no pharmacological actions. The 3-O-methylated metabolite was eliminated very slowly following oral administration of tolcapone, and its concentration approached a plateau level, which was in contrast to the situation following intravenous administration of tolcapone. It is thought that the oral dose of tolcapone receives a high exposure to MB-COMT in the intestinal muscle layer during its absorption, and tolcapone seems to form a complex with MB-COMT having a high affinity constant (i.e. a very low K_i). The fraction of the intravenous dose of tolcapone metabolized to the 3-O-methylated metabolite at 10 mg kg^?1 was 2·6%, whereas those of the oral doses, which were corrected by the bioavailability, were 5·4% for 20 mg kg^?1 and 2·7% for 40 mg kg^?1.     

Inhibitory Activity of Camptothecin Derivatives Against Acetylcholinesterase in Dogs and Their Binding Activity to Acetylcholine Receptors in Rats

Abstract— A camptothecin derivative, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), shows a potent antitumour activity in experimental tumour models and in clinical trials. However, CPT-11 induced early diarrhoea and vomiting at high dose levels in clinical studies and showed an acetylcholine-like action on the guinea-pig ileum and trachea. In the present study, we investigated the activities of camptothecin derivatives in inhibiting acetylcholinesterase (AChE) and in binding to muscarinic acetylcholine receptors (AChR). CPT-11 inhibited AChE and binding of the specific ligand to AChR with respective 50% inhibition concentrations of 0·2 and 5 μm . These inhibitions were induced by camptothecin derivatives having an amino group at the C-10 position (or the C-4 position of hexacyclic derivatives), but were not or were only slightly induced by the others. Early defecation and vomiting in dogs were observed after intravenous injection of DU-6596 and DU-6888, two hexacyclic derivatives having the aminomethyl group at the C-4 position, and of CPT-11. DU-6174, however, which has a hydroxy group at this position, induced no early defecation and little vomiting. Plasma concentrations of CPT-11, DU-6596 and DU-6888 after intravenous treatment at doses causing such early adverse effects were maintained for 1 h or longer at levels sufficient to inhibit AChE. These results suggest that the inhibition of AChE by camptothecin derivatives with an amino group at the C-10 position (or the C-4 position) relates to the early defecation or diarrhoea and vomiting.     

Prediction of transfusions in extremely low-birthweight infants in the erythropoietin era

BACKGROUND: The purpose of the present paper was to detect the clinical factors most predictive of red blood cell (RBC) transfusion in extremely low-birthweight (ELBW) infants in the recombinant human erythropoietin era. METHODS: Between 1995 and 2000, 66 ELBW infants were admitted to a level III neonatal intensive care unit. Fifty-four of 66 infants were eligible for enrollment in the present study. Infants were treated with erythropoietin 200 IU/kg per dose s.c. twice a week with 4-6 mg/kg per day iron supplement. RESULTS: The mean gestational age and birthweight were 26.5 +/- 2.1 weeks and 776 +/- 134 g, respectively. Ten of 54 ELBW infants (18.5%) died during the first 21 days. Eight of 10 dead infants (80.0%) and 27 of 44 surviving infants (61.4%) received one or more RBC transfusions. The overall requirement for RBC transfusions in the surviving infants was 3.0 +/- 3.2 per infant/hospital course (range: 0-9) . There were significant differences in gestational weeks, birthweight, initial hemoglobin value, 5 min Apgar score, phlebotomy loss, phlebotomy loss/birthweight, duration of mechanical ventilation, duration of oxygen supplement, and incidence of both intraventricular hemorrhage and chronic lung disease between the transfused and non-transfused group. The predictive variables, initial hemoglobin level (odds ratio [OR] 2.61; 1 g/dL), birthweight (OR 3.00; 100 g), and gestational week (OR 1.89; 1 week), were found to be most predictive for transfusion on logistic regression analysis. CONCLUSION: ELBW infants are still the population at greatest risk for repeated blood transfusions after introduction of erythropoietin treatment. If labor develops, it is often impossible to extend the pregnancy period, therefore efforts should be made to increase hemoglobin level at birth.     

A Case of Widely Split Double P Waves with Marked Intra-Atrial Conduction Delay

Widely Split Double P Wave. We report a 78-year-old man as the first documented case of double P waves separated by 400 msec on 12-lead ECG. These P waves had different polarities on lead V₁. The first P wave represented activation of the lateral wall of the right atrium, and the latter P wave represented activation of the nudial right atrium and the left atrium. Widely spaced double potentials were recorded craniocaudally along the line, presumably corresponding to the crista terminalis during sinus rhythm. For this to occur, conduction disturbance has to be present both in the upper and lower right atrium. Conduction disturbance in the upper right atrium would interrupt excitation from the sinus node to the medial wall, and conduction disturbance in the lower right atrium would interrupt excitation spreading from the lower lateral right atrium to the isthmus area where fragmented potentials were recorded. These multiple discrete lesions appear to constitute a unique electrical atriopathy in this patient.     

Developmental brain-stem pathology in sudden infant death syndrome

The brain-stems of control and sudden infant death syndrome (SIDS) infants were examined developmentally with Golgi and immunohistochemical methods. The development of dendritic spines changed dramatically from the prenatal to postnatal period in the ventrolateral medulla as well as in the reticular formation and vagal nuclei in controls, but persisted in SIDS infants. These observations suggest a delay in maturation of the meduallary respiratory neurons and transneuronal connection between the central chemoreceptor and neural respiratory center in SIDS. In addition, substance P (SP)-positive nerve fibers were increased in the pons of SIDS infants. An increased activity in the afferent SP neurons in SIDS may be due to chronic hypoxia as in brain-stem gliosis, and may be involved in cardiorespiratory regulation.     

MALIGNANT HEMANGIOENDOTHELIOMA

Background. The administration of interleukin-2 (il-2 ) has recently been reported to be favorable for treating malignant hemangioendothelioma (mhe ). Methods. Two patients with mhe responded well to intra-lesional injections of recombinant il-2 (ril-2 ) without major side effects. The purpose of this study was to characterize cells infiltrating the regressing tumor following ril-2 treatment. Immunohistochemical studies were performed on biopsy specimens taken from ril-2 -injected lesional skin. Results. It was shown that CD8⁺ lymphocytes and CD56⁺ natural killer (nk ) cells infiltrated at the ril-2 -injection sites, suggesting that these cells contributed to the tumor regression. In addition, MHE cells bore intercellular adhesion mole-cule-1 (icam -1) whose expression was augmented by rn-2 injections. Conclusions. These findings suggested, that ril-2 not only induces lymphokine-activated killer (lak ) cells and nk cells, but also facilitates these cytotoxic cells to adhere to MHE cells by enhancing icam -1 expression of tumor cells.