Retrograde intubation dacryocystorhinostomy for proximal and midcanalicular obstruction

Objective

Retrograde intubation of canaliculi during dacryocystorhinostomy can restore canalicular patency in cases otherwise managed with bypass tubes. The surgical technique and success for this procedure are discussed.

Comparative patterns of i-antigen expression, F-cell frequency and Hb A2 level in acute myeloid leukemia and in acute lymphoid leukemia

Hb F, Hb A₂ and i-antigen expression were investigated in adulthood acute leukemias. The study of i-antigen expression by immuno-agglutination and immunofluorescence showed that it is preferentially increased among AML patients. A similar result was obtained for F-cell frequency which was often increased in AML, while it was normal in ALL. Hb A₂ level was significantly lower in AML than in ALL. These differences between AML and ALL red cell patterns further suggest that the leukemic clone involves the erythroid lineage in AML but not in ALL.     

口服及静注乙醇后血中乙醇与β-羟丁酸,乙酰乙酸,乳酸及丙酮酸浓度关系的探讨:一项群体药效动力学的研究

目的 :应用群体药理学方法探讨血浆中乙醇浓度对 β 羟丁酸 ,乙酰乙酸 ,乳酸 ,丙酮酸 ,β 羟丁酸 乙酰乙酸 (H A)比值及乳酸 丙酮酸 (L P)比值变化的效应。方法 :给 14名健康成人口服剂量相当于1.0 2g·L-1总身体水的乙醇。在另一项实验中 ,给 8名健康成人静脉注射剂量相当于 0 .83g·L-1总身体水的乙醇。在服用乙醇后 380min采取静脉血测定乙醇 ,β 羟丁酸 ,乙酰乙酸 ,乳酸及丙酮酸的血浆浓度。在静注乙醇后 340min采血测定上述 5种物质的血浆浓度。结果 :在口服乙醇实验中 ,C0 为 6 6 .6±8.1mg·dl-1,显著低于 10 2mg·dl-1,(t检验 ,P <0 .0 0 1)。清除相斜率 β为 0 .2 2 9± 0 .0 5mg·dl-1·min-1。在静注实验中 ,C0 为 75 .6± 10 .9mg·dl-1,与 83mg·dl-1比较无显著性差异 ,β为0 .2 4 5± 0 .0 5mg·dl-1·min-1。在两项实验中 ,我们应用群体间接生理反应模型来拟合乙醇浓度对 β 羟丁酸 ,乙酰乙酸 ,乳酸 ,丙酮酸 ,β 羟丁酸 乙酰乙酸比值及乳酸 丙酮酸比值变化的效应 ,并得出各项参数。同时 ,我们发现 ,当乙醇的清除相结束时 ,H A比值尚未达最大值 ,说明在乙醇的零级代谢相时肝脏仍在产生NADH。乳酸和乙醇的关系曲线显示乳酸的变化呈现一种逆时钟方向的滞后。结论 :血L P比值不适合用作实     

高血压与临床很可能帕金森病关系的初步探讨

目的 探讨林县营养缺乏人群高血压与临床很可能帕金森病(Clinically Probable Parkinson’s disease，PPD)之间的关系，为早期防治帕金森病(PD)提供理论依据。方法 采用前瞻性队列研究方法。人群血压资料来源于1985年林县营养干预试验开始时研究对象的基线调查。病例的诊断，通过两个步骤完成，即第一步采用调查问卷与体格检查相结合的办法，对队列人群进行PPD的筛查，第二步对可疑病例，由中美神经科专家联合诊断，并依据英国帕金森病协会脑库临床诊断标准进行PPD的临床诊断。资料处理采用线性趋势检验，及非条件Logistic回归。结果 单因素分析显示：高血压与PPD有统计学关联，其RR值为1．648(1．147～2．368)；用年龄、性别、吸烟、饮酒等可能的混杂因素进行调整后，上述关联依然存在。分性别后统计显示，男性高血压与PPD无统计学关联。女性高血压与PPD统计学上有显著性相关，其RR值调整前为2．347(1．347～4．091)，经混杂因素进行调整后关联依然存在。随着血压的增高，其对应的RR值也随之增加，经线性趋势检验(X^2=11．325，P=0．003)，表明血压与PPD存在剂量-反应关系。结论 在林县营养缺乏地区，高血压是55岁以后女性居民罹患PPD的危险因素之一，并且患PPD的危险性随血压的增高而增加。     

少数民族葡萄糖-6-磷酸脱氢酶基因突变检测

目的 了解贵州省少数民族葡萄糖-6-磷酸脱氢酶(Glucose-6-phosphato dehydrogenase。G6PD)缺乏症的发生率、基因突变类型特点及分布特征。方法 对贵州省苗族、水族、瑶族2566人采用四氮唑蓝定性法初筛、G6PD／6PGD比值法验证，再经错配引物介导的聚合酶链反应／限制性酶切分析法检测中国人常见的基因突变型。结果 检出G6PD缺乏症175例，其中苗族检出G1388A突变7例、G1376T突变1例、A95G突变6例、C1024T突变8例；水族检出G1388A突变12例、G1376T突变24例、A95G突变9例、C1024T突变2例；瑶族检出G1388A突变15例、G1376T突变7例。结论 贵州省是G6PD缺乏症的高发区，贵州省苗族、水族、瑶族中都存在G1388A、G1376T这两种中国人常见G6PD突变型。为了解贵州省少数民族G6PD缺乏症的分布特征提供了原始数据。     

韶关市新生儿G6PD缺乏的早期诊断及其防治

目的对新生儿筛查检出的G6PD缺陷与高胆的关系进行临床研究,探讨G6PD缺陷的早期诊断及其高胆的防治方法。方法用荧光斑点法对新生儿进行G6PD缺陷定性筛查,阳性病例用G6PD/6PGD比值法进一步确诊,临床观察本组100例G6PD缺陷的高胆病程。结果本组G6PD缺陷新生儿55.0%发生了高胆;高胆91.4%于生后2～3天起病;重度高胆占29.1%,仅见于重度G6PD缺陷者;轻、中度缺陷者高胆程度轻;催产素的应用、感染、早产等因素可能诱发或加重高胆。结论G6PD缺陷者新生儿高胆发病率高,发病早,程度重,危害大,高胆程度与G6PD缺陷程度和诱发因素有关,而脐血筛查可能是G6PD缺陷早期诊断的惟一途径。高胆预防措施包括产前孕母服鲁米那、维生素E;产时避免诱发因素及生后口服鲁米那,肌注维生素E,有黄疸者及早光疗。     

防治痴呆新药的构效关系研究

阿尔茨海默病、帕金森病和血管性痴呆是严重危害老年人生命健康的多发病。目前临床应用的防治痴呆药物的作用机制主要涉及改善胆碱能神经递质、激动多巴胺(DA)受体、阻滞N-甲基-D门冬氨酸(NMDA)受体和改善脑血管功能等。综述了近年来报道的防治痴呆新药的构效关系研究进展。     

Estimated Glomerular Filtration Rate —A More Stable Indicator than Creatinine Clearance in Peritoneal Dialysis Practice

Objective: The usefulness of estimated glomerular filtration rate may not be restricted to pre-dialysis patients, since we reported that estimated glomerular filtration rate was well correlated with measured total creatinine clearance in peritoneal dialysis patients. To clarify the clinical usefulness of estimated glomerular filtration rate as a parameter for peritoneal dialysis adequacy, we retrospectively surveyed estimated glomerular filtration rate and total creatinine clearance in peritoneal dialysis patients treated at JA Toride Medical Center.Patients and Methods: A total of 114 data sets of estimated glomerular filtration rate and total creatinine clearance from 21 PD patients treated at JA Toride Medical Center were collected from November 2010 to October 2011. The patients consisted of 15 men and six women with an average age of 66.6 ± 12.6 years (46–95 years old). The average number of samples was 5.4 ± 1.5 (2 to 7) per patient.Results: The collected data showed less correlation of estimated glomerular filtration rate and total creatinine clearance (r. = 0.435) than that of a previous cross-sectional study (r. = 0.836). As reported in pre-dialysis patients, the differences between estimated glomerular filtration rate and total creatinine clearance were correlated with total creatinine excretion in urine and PD effluent (r. = 0.821). The differences were also correlated with normalized protein catabolic rate, which was one of the main determinant factors for total creatinine excretion (r. = 0.636). A similar tendency was apparently observed in one patient with poor compliance to diet therapy and fluctuating dietary intake. From the analysis of these data, serum creatinine seemed to fluctuate less possibly due to compensatory capacity of the residual renal function in small solute clearance.Conclusions: Consequently, estimated glomerular filtration rate was turned out to be a more stable parameter than total creatinine clearance, which might be a desirable feature in long-term follow-up of peritoneal dialysis patients.     

Immuno-pharmacodynamics for evaluating mechanism of action and developing immunotherapy combinations

Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule). Clinical pharmacodynamic (PD) biomarkers will be useful endpoints for confirming drug mechanism of action, evaluating combination therapies for synergy or antagonism, and identifying optimal dosage regimens. In contrast to conventional PD in which drug action occurs entirely within a single target cell (ie, is self-contained within the malignant cell), immunotherapy involves a complex mechanism of action with sequential steps that propagate through multiple cell types, both normal and malignant. Its intercellular pharmacology begins with molecular target engagement either on an immune effector cell or a malignant cell, followed by stimulatory biochemical and biological signals in immune effector cells, and then finally ends with activation of cell death mechanisms in malignant cells lying within a certain distance from the activated effector cells (immune cell–tumor cell proximity). Evaluating such “trans-cellular pharmacology,” in which different steps of drug action are distributed across multiple cell types, requires novel microscopy and image analysis tools capable of quantifying PD-biomarker responses, mapping the responses onto the cellular geography of the tumor using phenotypic biomarkers to identify specific cell types, and finally analyzing the spatial relationships between biomarkers in the context of each cell’s biological role. We have termed this form of nearest neighbor image analysis of drug action “proximity PD microscopy,” to indicate the importance of the location of the PD-biomarker response within the cellular landscape of a tumor specimen. We discuss herein the major modes of immunotherapy, and lay out a blueprint for using PD assessment to optimize dosage regimens of single agents and guide development of combination immunotherapy regimens, using PD1/PD-L1 immune checkpoint inhibition as a case study.