Dose-intensive,Time-compressed Procarbazine,CCNU, Vincristine (PCV) with Peripheral Blood Stem Cell Support and Concurrent Radiation in Patients with Newly Diagnosed High-grade Gliomas

The dose intensity of the PCV regimen can be doubled using peripheral blood stem cell (PBSC) support. This study sought to determine the feasibility of giving dose-intensive PCV concurrently with radiation therapy. Twelve patients, age 3.2–22.7 years, median 7.5 years, with newly diagnosed high grade gliomas were enrolled. Diagnoses included diffuse intrinsic brainstem gliomas (BSG) (n=6), glioblastoma (n=4), anaplastic astrocytoma (n=2). PBSCs were harvested prior to chemotherapy with G-CSF priming. Chemotherapy consisted of CCNU 130 mg/m² and vincristine 1.5 mg/m² on day 0, and procarbazine 150 mg/m² on days 1–7. PBSCs were reinfused on day 9 of each course. Four courses of chemotherapy were administered every 28 days or when blood counts recovered. The first course was administered the week prior to RT, the second course began on week 3 of RT and the third and fourth course were given after RT. Hematologic toxicity was mild and the majority of courses were given on schedule. Five of six patients with diffuse BSG showed clinical improvement and three showed a radiographic response; however, only one remains alive 12+ months from diagnosis. All four patients with non-brainstem large-volume tumors showed clinical deterioration and radiographic progression during or shortly after RT. MRI scans showed massive edema and enhancement. Median time to radiographic progression was five months. Median overall survival was 11 months. We conclude that dose-intensive, time-compressed PCV given concurrently with large-volume RT appears to result in unacceptable toxicity in patients with large residual tumors.     

High dose ifosfamide, doxorubicin, dacarbazine and G-CSF for patients with metastatic or locally advanced soft tissue sarcoma

SOFTTISSUESARCOMAS(STS)accountforapproximatelyl%ofadultmalignanciesandl5%ofpediatricmalignancies.Theuseofradicalsurgeryisthem0steffectivemethodfortreatmentofearystageSTS.Unfortunately,manypatientsarediagnosedlate0rreceiveinadequateprimarysurgerysothatmetastasesultimatelyoccULAlthoughsalvagetreatthentbyexcisionofthemetastasesissuccessfulforsomepatients,themajoritywilldiefromprogressivedisease.Doxorubicin(Adriamycin,ADR)isthemostactivesingleagentinsofttissuesarcomas,witharesponserate…     

大剂量甲氨蝶呤预防儿童中枢神经系统白血病的作用

目的探讨大剂量甲氨喋呤（NDMTX）对急性淋巴细胞白血病（ALL）儿童中的中枢神经系统白血病（CNSL）的预防作用。方法12例病儿接受了56次HDMTX（每次3．0g／m2）治疗。应用荧光偏振免疫法测定MTX的血清和脑脊液浓度。结果血清MTX的最高浓度为（0．87～1．23）×10-4mol／L,用药24h后有效浓度仍在（1．0～70） ×10-7mol／L范围内。脑脊液的MTX浓度在（2.0～8．8）×-7mol／L,足以杀灭中枢神经系统内的白血病细胞,除一例出现严重中毒外,其余病例不良反应均较轻。9例坚持治疗18个月（6～66个月）者,除一例复发外,8例连续完成缓解。结论NDMTX治疗有利于减少ALL儿童CNSL的复发,有提高长期无病生存率的作用。     

Characterization of the discriminative stimulus effects of GABAA receptor ligands in Macaca fascicularis monkeys under different ethanol training conditions

Rationale: Some evidence suggests an involvement of nucleus accumbens in spatial learning. However, it is controversial whether the mesoaccumbens dopaminergic pathways play a specific role in the acquisition of spatial information. Objective: The goal of these experiments was to investigate the effect of dopaminergic manipulations in the nucleus accumbens on a non-associative task designed to estimate the ability to encode/transmit spatial and non-spatial information. Methods: The effects of focal administrations of the D1 and D2 dopamine receptor antagonists, SCH 23390 (6.25, 12.5, 50 ng/side) and sulpiride (12.5, 50, 100 ng/side), respectively, and dopamine (DA; 1.25 and 2.5 μg/side) into the nucleus accumbens were studied on reactivity to spatial and non-spatial changes in an open field with objects. Results: Both SCH 23390 and sulpiride impaired reactivity to spatial change. However, several differences were found in the effects induced by the two DA antagonists. SCH 23390 did not affect locomotor activity and only slightly impaired exploration of the novel object. On the contrary, the D2 antagonist, induced a general, dose-dependent, impairment on all variables measured. Local administration of DA increased locomotor activity, but did not affect reactivity to spatial and non-spatial changes. Conclusions: These results demonstrate a facilitatory role of mesoaccumbens dopamine in the acquisition of spatial information. Moreover, they suggest that nucleus accumbens D1 DA receptors, play a more selective role in the modulation of spatial learning than accumbens D2 DA receptors. Electronic Publication     

中心及外周呼吸阻力的评估方法探讨

目的探讨总呼吸阻力分成中心呼吸阻力（Ｒｃ）和外周呼吸阻力（Ｒｐ）的评估方法．方法用强迫振荡技术把Ｍｅａｄ呼吸模型的有效阻力分成中心呼吸阻力（Ｒｃ）和外周呼吸阻力（Ｒｐ）,将其值分别与理论预置值对照,以符合程度评定该分离方法的合理性．结果人的Ｒｃ、Ｒｐ分离值误差最大为３％,狗的Ｒｃ、Ｒｐ分离值误差最大为７％,一般误差在１％左右．实验结果与理论预期基本一致．归一化频率ｆ／ｆ１范围对于正常人以０．０６～０．６为佳,狗则以０．１６～１．６为最好．当Ｒｃ增加时,该频段范围不受影响．而Ｒｐ的增加则使归一化频率ｆ／ｆ１朝增加方向移动．结论利用强迫振荡有效阻力的频率依赖性可以进一步分离中心和外周呼吸阻力．     

抗氧化中药的毒性试验

对抗氧化中药进行毒性试验研究。结果表明：急性试验小鼠和大鼠的ＬＤ５０分别为３６６９ｍｇ／ｋｇ,３８６９ｍｇ／ｋｇ（Ｂ．Ｗ＿均大于人每日口服剂量的２０倍以上,提示本品毒性甚微。长期毒性试验在相当于人每日每量２０倍,连续９０ｄ后出现中毒症状,如全重增长延迟, 血,肟肾实质变性等,但用一般治疗剂量,则无明显储积毒性作用。     

川芎嗪和川芎注射液对麻醉开胸犬血流动力学的影响

目的：探讨川芎嗪（ＴＭＰ）与母药川药注射液之间的药效关系。方法：以８ｍｇ·ｍｇ＾－１的磷酸ＴＭＰ（ＴＭＰＰ）注射液和川芎注射液（０．１ｇ·ｋｇ＾－１）单独和混合,从健康麻醉开胸犬的心房内注射;并测定后者血清中ＴＭＰ浓度,换算后以低剂的心房内注射;并测定后者血清中ＴＭＰ浓度,。换算后以低剂量０．１ｍｇ·ｋｇ＾－１ＴＭＰＰ注射。结果：ＴＭＰＰ引起明显的ＨＲ增块,ＬＶＳＰ,ＬＶｄＰ／ｄｔｍａｘ内恢复正常     

The cause and prevention of human birth defects: What have we learned in the past 50 years?

ABSTRACT This review article dealig with the subject of “The Cause and Prevention of Human Birth Defects” was prepared in celebration of the 40th anniversary of the Japanese Teratology Society. It begins with recollections of some of the important contributions of Japanese scientists in the fields of teratology and embryology and a summary of the many scientific and medical accomplishments of the past 50 years in the fields of teratology, genetics, developmental biology, epidemiology and genetics. The review includes a summary of the drugs, chemicals and physical agents that have been documented to result in congenital malformations and reproductive effects when pregnant women are exposed during pregnancy. The principles of teratology were also summarized and emphasize that 1) no teratogenic agent can be described qualitatively as a teratogen, since a teratogenic exposure must include not only the agent, but also the dose and the time in pregnancy when the exposure occurs. 2) Even agents that have been demonstrated to result in malformatins cannot produce every type of malformation. 3) Known teratogens can be presumptively identified by the spectrum of malformations they produce. 4) It is easier to exclude an agent as a cause of birth defects than to definitively conclude that it was responsible for birth defects. 5) When evaluating the risk of exposures, the dose is a crucial component in determining the risk. 6) Teratogenic agents follow a toxicological dose response curve. This means that each teratogen has a threshold dose, below which, there is no risk of teratogenensis, no matter when in pregnancy the exposure occurred. 7) The evaluation of a child with congenital malformations connot be adequately performed unless it is approached with the same scholarship and detail, as is any other complicated medical problem. 8) Each physician must recognize the consequences of providing erroneous reproductive risks to pregnant women exposed to drugs and chemicals during pregnancy or alleging that a child's malformations are due to an environmental agent without performing a complete and scholarly evaluation.