Elimination of malignant clonogenic cells from human bone marrow using multiple myeloid cell-specific monoclonal antibodies and complement.

Single or combined monoclonal antibodies (McAbs) Zh53, Zh820, and Zh2-1 have been used to eliminate malignant clonogenic cells from human bone marrow. The test of cytotoxicity showed that all of these McAbs could express high specific cytotoxic action against HL-60 cells and were selectively complement-dependent cytotoxic to various types of fresh leukemic cells. Clonogenic assay detected that single treatment with antibody and rabbit complement (RC) could reduce clonogenic units of HL-60 cells by more than 2 logs and two treatments reduced clonogenic units by more than 4 logs. However, combination of 2 McAbs could reduce clonogenic units by 4-5 logs. The data suggest that multiple treatments with McAbs and RC or a combination of 2 McAbs are more effective than a single treatment in eliminating clonogenic tumor cells. Treatment of normal human bone marrow with Zh53, Zh2-1 and RC did not produce a loss of normal CFU-GM, but treatment with Zh820 reduced the clonic units of normal CFU-GM by 24%.

     

Studies on Toxicity of Nitroquine-Dapsone Compound and Therapeutic Effects of Folic or Folinic Acid on Toxicated Animals

The toxic effects of nitroquine-dapsone compound(NQD)in mice and dogs were studied.The therapeutic index of NQDin mice is 1911,the greatest among the 6 antimalarials tested.Thetoxic effects of NQD(50 mg/kg/day for 3 days per os)and nitro-quine in dogs were manifested by injuries on the adrenal cortexand intestinal epithelium.When folic acid(4 mg/kg/day for 4 days)or calcium leucovorinum(0.3 mg/kg/day for 4 days)were usedconcomitantly with NQD,the death rate and the incidence of dia-rrhea in the toxicated dogs were greatly reduced,the injury on theintestinal epithelium was much milder,and the goblet cells weremuch more numerous than those without treatment.The results suggestthat folic acid and calcium leucovorinum can protect the undifferen-tiated cells in the intestinal crypts from being injured by NQD.     

浅谈医院人性化管理

文章从医院人性化管理的定义,僵硬制度化管理的弊端,医院人性化管理的作用,怎样人性化管理职工和患者,阐明了如何实现医院人性化管理的问题。     

Electrophysiologic evaluation of Emery-Dreifuss muscular dystrophy. A single fiber and quantitative EMG study

A 16-year-old boy, the only affected member of the family, noticed early onset contracture of the elbows, and developed slowly progressive humeroperoneal weakness and atrophy, and bilateral equinus. The severe restriction of the forward flexion of the neck and thoracolumbar spine, resembled a rigid spine syndrome. An electrocardiogram showed atrioventricular conduction abnormalities. Muscle biopsy was consistent with mild myopathy. The overall conventional findings of a detailed electromyographic study in the limbs and erector trunci muscles, as well as the results of conduction velocity, automatic analysis of the voluntary pattern and single fiber electromyography studies were consistent with myopathy, although some atypical findings were found. The controversy about neurogenic and myopathic features in Emery-Dreifuss disease is discussed. The unspecific value of the flexion limitation of the spine, and the uncertain nosological position of the rigid spine syndrome are also commented.     

NEUROTROPIN IMMUNOSTIMULATING ACTION ON IMMUNOCOMPETENT CELLS

Neurotropin (NSP) is an extract isolated from the skin of rabbits inoculated with vaccinia virus. The present study examines the possible action of NSP on the number and function of immunocompe tent cells in mice. The experiment showed that NSP had no effect on both T and B lymphocytes of nor- malimmunized mouse spleen. The degree of plaque forming cell reaction and titre of specific antibody showed no significant differences when the NSP treated group and controls were compared. How- ever, NSP exhibited promotive effect on specific antigen binding cells in the early stage of immune responses. It was also noted that the rosette forming capacity of human T lymphocytes in vitro was restor- ed markedly by NSP. These results suggest that NSP possesses certain immunostimulating activity, particularly on the specific antigen binding cells and human T lymphocytes.     

Computational modeling to predict effect of treatment schedule on drug delivery to prostate in humans.

PURPOSE: To evaluate a computational approach that incorporates experimental data in preclinical models to depict doxorubicin human tissue pharmacokinetics. EXPERIMENTAL DESIGN: Beagle dogs were given 2 mg/kg doxorubicin as i.v. bolus, 4-h infusion, or 96-h infusion. Concentrations in plasma, prostate (target tissue), heart (toxicity), and major tissues for disposition were determined and modeled. Model parameters were obtained after the bolus injection with model validation based on the 4-h and 96-h infusion data. Clinical pharmacokinetic data and scale-up gave doxorubicin profiles in human prostate and heart. RESULTS: In agreement with in vitro results, tissues were best modeled with two compartments, one rapidly and one slowly equilibrating. The developed tissue distribution model predicted concentrations for all three administration regimens well, with an average deviation of 34% (median, 29%). Interspecies scale-up to humans showed that the change from a bolus injection to a slow, 96-h infusion (a) had different effects on the drug partition and accumulation in heart and prostate, and (b) lowered the peak concentration in the plasma by approximately 100-fold but had relatively little effect on maximal heart concentration ( approximately 33% lower). The simulated drug exposure in a human prostate was above the exposure required to inhibit tumor proliferation but was 30 to 50 times below that needed for cell death. CONCLUSION: The present study shows a computation-based paradigm for translating in vitro and in vivo preclinical data and to estimate and compare the drug delivery and pharmacokinetics in target tissues after different treatment schedules.     

儿童频繁瞬目征的病因及综合治疗

[目的]探讨儿童频繁瞬目征的发病原因及其治疗措施。[方法]随机抽取148例门诊频繁瞬目征患儿，对其生活习惯、眼部情况进行详细询问并进行病因分析及综合治疗。[结果]通过克服不良生活习惯、去除谤因、调节心理和综合治疗措施，148例频繁瞬目征惠患儿经2周～5周的治疗，115例患儿治愈，28例好转，5例无效。[结论]频繁瞬目征与玩电脑、看电视及偏食有一定关系，针对性综合治疗可获得较满意的疗效。     

Performance and comparison of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese Type 2 diabetic population.

AIMS: Our aim was to assess performances of the Cockcroft-Gault and simplified Modification of Diet in Renal Disease (MDRD) formulae in estimating glomerular filtration rate (GFR) in Chinese diabetic populations and their association with vascular risks. METHODS: A total of 1009 patients with Type 2 diabetes were categorized into low estimated GFR groups (GFR < 60 ml/min/1.73 m(2)) and control groups by the two equations. The performances of these formulae were assessed at different stages of kidney function. Carotid artery intima-media thickness (IMT) and the prevalence of diabetic retinopathy or albuminuria were compared among the groups. The ability of these formulae to identify established vascular risk markers using sensitivity, specificity, positive and negative predictive values were also compared. RESULTS: The prevalence of low estimated GFR was 32.7% with the Cockcroft-Gault formula and 5.2% with the MDRD formula, respectively. In low estimated GFR subjects by the MDRD formula, IMT was significantly thicker than those by the Cockcroft-Gault formula (1.2 mm vs. 1.0 mm; P < 0.05), with a higher prevalence of albuminuria (78.4 vs. 52.8%, P < 0.05) and diabetic retinopathy (46.5 vs. 30.5%; P < 0.05). The Cockcroft-Gault formula gave a specificity of 71.7% and a sensitivity of 37.0%, and the MDRD formula gave a specificity of 96.6% and a sensitivity of 7.9% in estimating low GFR relevant for established vascular risks. CONCLUSIONS: These formulae performed differently in Chinese diabetic populations. The simplified MDRD formula is minimally superior to the Cockcroft-Gault formula for its high specificity and positive predictive values in estimating low GFR relevant for vascular risks.     

Intraprostatic chemotherapy: distribution and transport mechanisms.

PURPOSE: The present study evaluated the tissue distribution and targeting advantage of intraprostatic chemotherapy. EXPERIMENTAL DESIGN: We studied the delivery and spatial distribution of a fluorescent drug, doxorubicin, in the prostate of beagle dogs, after intraprostatic or i.v. administration. Drug concentrations were measured using high-performance liquid chromatography and confocal fluorescence microscopy. RESULTS: I.v. and intraprostatic injections yielded qualitatively and quantitatively different doxorubicin distribution in the prostate. A relatively homogeneous distribution was found after i.v. administration, whereas intraprostatic injection yielded a highly heterogeneous distribution with >10-fold higher concentrations localized in a cone-shaped glandular lobule bound by fibromuscular stroma, compared with other parts of the prostate. Compared with i.v. injection, intraprostatic injection yielded, on average, approximately 100-fold higher tissue-to-plasma concentration ratio, ranging from 963-fold near the injection site to 19-fold in the contralateral half of the prostate. The drug distribution within the prostate further suggests an important role for acinar flow in intraprostatic drug transport. CONCLUSIONS: Intraprostatic administration represents a viable option to deliver high drug concentrations within the prostate. The results further suggest the fibromuscular stroma separating the prostatic lobules as a major barrier to drug transport and convective flow as an important drug transport mechanism in the prostate.     

曼氏血吸虫与日本血吸虫交叉免疫原性的血清学实验研究

以曼氏血吸虫的虫卵和成虫免疫家兔后所产生的特异性抗体,可用以日本血吸虫虫卵、尾蚴和成虫为抗原分别进行的COP,CHR和ELACIEP测出,表明两种人体血吸虫存有显著的交叉抗原成分。应用此种血清交叉反应性,以检测抗异种人体血吸虫的抗体,似有效而可取的,可用以辅助诊断援外回国人员是否感染国外人体血吸虫病。