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。     

屈颈MRI对青年性上肢远端肌萎缩症的诊断价值

目的评价屈颈MRI对青年性上肢远端肌萎缩症的诊断价值。方法男性患者5例，平均年龄21岁，临床表现为一侧或两侧上肢远端肌萎缩。对照组为健康志愿者，21岁男性8例。2组均行常规及屈颈颈椎MR平扫，矢状、轴面SET1WI、T2WI、液体衰减反转恢复（FLAIR）序列扫描。结果常规颈椎扫描：5例患者下段颈髓变细；屈颈位MR扫描：下颈段颈6以下脊髓前屈、变扁平，矢状径4～6mm，硬膜囊后壁前移，硬膜后间隙明显增宽，可见多发条状、迂曲流空信号影及软组织信号。对照组：常规扫描，下颈段脊髓（颈6～胸2）可见颈膨大，屈颈位脊髓略变细（6～7mm），硬膜囊后壁无前移，硬膜后间隙未见扩张血管影。结论屈颈MRI有助于显示下颈段脊髓及硬膜囊改变，结合临床资料可准确诊断青年性上肢远端肌萎缩症。     

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.     

Paradigm shift in hydrocephalus research in legacy of Dandy’s pioneering work: rationale for third ventriculostomy in communicating hydrocephalus

Objective This study aims to question the generally accepted cerebrospinal fluid (CSF) bulk flow theory suggesting that the CSF is exclusively absorbed by the arachnoid villi and that the cause of hydrocephalus is a CSF absorption deficit. In addition, this study aims to briefly describe the new hydrodynamic concept of hydrocephalus and the rationale for endoscopic third ventriculostomy (ETV) in communicating hydrocephalus. Critique The bulk flow theory has proven incapable of explaining the pivotal mechanisms behind communicating hydrocephalus. Thus, the theory is unable to explain why the ventricles enlarge, why the CSF pressure remains normal and why some patients improve after ETV. Hydrodynamic concept of hydrocephalus Communicating hydrocephalus is caused by decreased intracranial compliance increasing the systolic pressure transmission into the brain parenchyma. The increased systolic pressure in the brain distends the brain towards the skull and simultaneously compresses the periventricular region of the brain against the ventricles. The final result is the predominant enlargement of the ventricles and narrowing of the subarachnoid space. The ETV reduces the increased systolic pressure in the brain simply by venting ventricular CSF through the stoma. The patent aqueduct in communicating hydrocephalus is too narrow to vent the CSF sufficiently.     

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.