A ten-year-old autistic girl with neuroleptic malignant syndrome caused by neuroleptic agents

We reported a ten-year-old autistic girl who had developed neuroleptic malignant syndrome (NMS) caused by administration of neuroleptic agents, haloperidol and chlorpromazine, because of her behavioral disorders. She had fever (38.4 degrees C) and elevated CK (796 IU). Her extrapyramidal symptoms and autonomic disturbance improved gradually after discontinuation of these drugs. However, altered consciousness did not change for three months despite treatment with L-DOPA, bromocriptine, dantrolene Na, biperiden, diltiazeM HCL and diazepam. Administration of amantadine HCL dramatically cleared not only the persistent symptom but also extrapyramidal symptoms and autonomic disturbance. She recovered from NMS one month later. The study of this case indicated that these neuroleptic drugs could cause NMS also in children. Therefore, the use of them in children with behavioral problems should be carefully evaluated clinically. It was concluded that NMS in this case occurred due to a defective dopamine release from presynaptic vesicles because L-DOPA was not effective and amantadine HCL was effective against these symptoms.     

Ovariectomy Increases in vivo Luteinizing Hormone-Releasing Hormone Release in Pubertal, but not Prepubertal, Female Rhesus Monkeys

In pubertal, but not prepubertal, monkeys ovariectomy (OVX) results in an elevation of circulating luteinizing hormone (LH) levels. To determine if the castration-induced LH increase in pubertal monkeys is due to an increase in pulsatile LH-releasing hormone (LHRH) release, effects of OVX on in vivo LHRH release in the stalk-median eminence were examined in fully conscious monkeys using a push-pull perfusion method. The average ages (± SEM) of female rhesus monkeys in each group at OVX were 14.5±0.6 months (n = 6; prepubertal), 25.0±1.3 months (n = 5; early pubertal) and 37.8 ± 2.1 months (n = 6; midpubertal). Perfusate samples from the stalk-median eminence were obtained in 10-min fractions for 6 h in the morning (0600 to 1200 h) and 6 h in the evening (1800 to 2400 h), from the same subjects before OVX, and at 29 days and approximately 100 days after OVX. LHRH levels in perfusates were measured by radioimmunoassay. LH levels throughout the experiment were monitored by periodic blood sampling. OVX resulted in a significant LH increase in early and midpubertal monkeys (P> 0.001 for both), but not in prepubertal monkeys. Similarly, OVX in early and midpubertal monkeys increased mean LHRH release when examined 29 days after surgery (P> 0.05 and P> 0.01, respectively). The OVX-induced LHRH increases in early and midpubertal monkeys remained elevated at approximately 100 days postcastration. Furthermore, it was found that effects of OVX on the increased LHRH release were primarily due to the elevation of basal release and pulse amplitude, but not pulse frequency. In contrast, OVX did not cause any significant effects on pulsatile LHRH release in prepubertal monkeys. The results indicate that an increase in LHRH release and a concomitant increase in circulating LH occurs after OVX in pubertal monkeys, but not in prepubertal monkeys. These data are consistent with the hypothesis that the low level of LH in circulation before the onset of puberty is due to a low amount of LHRH release which is independent of ovarian steroid feedback and that the maturity of the neuronal control system for the pulsatile LHRH release is responsible for the onset of puberty. After the onset of puberty, the negative feedback of ovarian steroid hormones becomes important to the regulation of gonadotropin release.     

Cooperative study of postoperative long-term adjuvant therapy of breast cancer. First study of a series--comparative study between postoperative tegafur administration and no adjuvant chemotherapy

A prospective randomized study was performed in 22 institutions from July 1978, to evaluate the efficiency of long-term adjuvant chemotherapy with tegafur alone for primary breast cancer. Five hundred and eighty-seven eligible patients, classified into T1a, T2a, T3a, N0, N1a, N1b, and M0 were divided into two groups: Group A, radical mastectomy receiving no adjuvant chemotherapy; and Group B, radical mastectomy followed by 4 courses of adjuvant chemotherapy, each one consisting of daily administration of tegafur 600 mg p.o. for 8 weeks and 4 weeks rest. At the 66th month of median follow up time, there were no differences between the two groups on 5 year cumulative survival and disease free survival rate. In subgroup patients who have histologically 1-3 axillary involvements, there seemed to be a more meaningful prolongation of the disease-free interval in group B than in group A (logrank test; p = 0.11 generalized Wilcoxon test; p = 0.13).     

Surgical adjuvant chemotherapy with mitomycin C and cyclophosphamide in Japanese patients with breast cancer

A controlled trial of surgical adjuvant chemotherapy for breast cancer was carried out using 551 Japanese patients. Single or combined treatment with mitomycin C (0.2 mg/kg i.v. three times within five days postoperatively) and cyclophosphamide (100 mg postoperatively daily for four months or longer) was used after radical surgery. In patients of the chemotherapy group with one to three lymph nodes involved in the axilla, the five-year cancer-free survival rate was 84.8% compared with 57.3% in the control group (P < 0.05), and the five-year cumulative recurrence in distant sites was 5.1% compared with 31.1% in the control (P < 0.05). The effectiveness of chemotherapy was much less marked in patients without nodal metastasis and with four or more nodes involved. Histologically, scirrhous cancer was the type that responded most favorably to chemotherapy, even in patients without axillary involvement. Premenopausal patients benefited more than postmenopausal patients from chemotherapy. A combination of mitomycin C and cyclophosphamide was more effective than their use singly. The present chemotherapy regimen was effective primarily in moderately advanced stages of breast cancer with decreased incidence of distant metastasis.     

Anterior hypothalamic lesions and pubertal development in female rhesus monkeys

Electrolytic lesions were made in the anterior hypothalamus of 8 prepubertal female rhesus monkeys, aged 1.1-1.7 years. Six unoperated females served as controls. No effects were found of the lesions upon age and body weight at menarche or at first ovulation, as estimated by blood levels of progesterone and laparoscopic observations. From these findings it appears that the neural control of puberty in the female rhesus may not be exerted through the anterior hypothalamus, in contrast with the rat and ferret. Further, an attempt was made to identify biometric correlates of hormonal changes during puberty. Firstly, the well known dip in growth rate, about 0.4 years before menarche, was observed. Secondly, there was a marked spurt in growth of the nipples starting at 0.2 years before menarche. The close temporal association between accelerated nipple growth and menarche suggests that both of these developmental characteristics result from changes in (presumably ovarian) steroid hormone secretion.     

Effects of liquid crystal-related compounds on human megakaryocytopoiesis and thrombopoiesis

In the present study, the effects of liquid crystal-related compounds on the megakaryocytopoiesis and thrombopoiesis were evaluated in vitro using CD34+ cells prepared from human placental and umbilical cord blood (CB). About 20 kinds of compounds were tested for their effects on the clonal growth of CB CD34+ megakaryocytic progenitor cells (CFU-Meg) in plasma clot culture. The compounds, dissolved in DMSO, were added to the cultures within a concentration range of 10-100 nM. When used alone, none of the compounds supported the clonal growth of CFU-Meg. However, when thrombopoietin (TPO) was used as a growth factor, three compounds increased CFU-Meg clonal growth significantly, producing approximately 1.3-1.4 fold increases in the total number of megakaryocyte colonies in comparison with the control. These compounds promoted mainly mature CFU-Meg-derived small colonies, suggesting that their target is relatively mature CFU-Meg. These effective compounds were examined in liquid culture supplemented with TPO alone for 14 days. Although there was no evident promotion of the total number of cells harvested from the culture, two compounds suppressed cell growth significantly. Only one compound enhanced the generation of CFU-Meg in the harvested cells. Although these results do not indicate a strong correlation between the chemical structure of each compound and biological effectiveness, the incorporation of phenylpyridine and phenylpyrimidine and binding of a hydroxyl residue into the structure may play an important role in the activity. Thus, liquid crystal-related compounds whose biological action was previously unknown have been shown to act as regulators of hematopoiesis.