Quantitative evaluation of adhesive properties and drug-adhesive interactions for transdermal drug delivery formulations using linear solvation energy relationships.

This paper describes the results of the application of linear solvation energy relationships (LSERs) to quantitatively characterize the properties of adhesives and to evaluate the degree of drug-adhesive interaction in transdermal drug delivery formulations. Probe solutions were prepared in acetonitrile (ACN) for a set of probe compounds with different physicochemical properties, and were used to swell the adhesives for subsequent probe molecule-adhesive interactions. The degree of the interactions was measured by the 'sorbed' amount of probe molecules. Based on LSERs, the 'sorbed' amounts were linearly correlated with their properties. The corresponding coefficients reflect the differential interactions of these molecules with the adhesive and ACN, and are quantitative indications of the adhesive properties. Two different transdermal acrylate adhesives (isooctyl acrylate/acrylamide/vinyl acetate in the weight ratios of 75/5/20 and isooctyl acrylate/2-hydroxyethyl acrylate/vinyl acetate in the weight ratios of 58/20/18) were selected for the evaluation of the methodology. It is concluded that the first adhesive is more basic and hydrophobic, which is consistent with the use of acrylamide monomer and significant amount of isooctyl acrylate. The second adhesive is more acidic and polarizable due to a relatively high amount of the 2-hydroxyethyl acrylate. Additionally, the 'sorbed' amount can be regarded as an interaction parameter or index between a drug molecule and the adhesive. Finally, this parameter is expected to correlate with the thermodynamic properties of transdermal formulations such as drug solubility, diffusion coefficient, release rate, and maybe skin permeation rate.     

高等医学院校医学化学教材改革的几点思考

医学的发展已进入分子水平，医学生必须具有扎实的化学基础才能适应专业学习及临床、科研工作的需要。现行医学化学教材大多沿用几十年前的模式，部分内容陈旧滞后，实用性不强。面对现实，改革势在必行。我们认为，突出重点、注重实用、体现医学特色应作为改革的方向。     

持续压力超负荷对兔左心室细胞凋亡的影响

OBJECTIVE: To study the effect of chronic pressure overload on the apoptosis of the left ventricle myocytes in rabbits. METHODS: Rabbit models of chronic pressure overload-induced heart failure were prepared in which dynamic changes of apoptotic myocytes in the left ventricle were observed by way of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. RESULTS: Only a few apoptotic cells was observed in the sham-operated group, while in the experimental group, the apoptotic left ventricle myocytes significantly increased after operation, presenting a peak level between day 3 and day 7. Seven days after the operation, the apoptotic myocytes began to decrease and till day 14, the apoptotic cell number had been smaller than that measured on day 1. When signs of heart failure set in, the apoptotic myocytes were again increased (P<0.001). CONCLUSION: During chronic pressure overload, myocyte apoptosis in the left ventricle is elevated at the early stages and undulates subsequently, with the peak occurring before hypertrophy is obvious.     

Electrophysiologic target localization in posteroventral pallidotomy

Summary The current interest in stereotactic posteroventral pallidotomy (PVP) for treating Parkinson's disease and the variability of published results have raised questions regarding techniques for target localization. In our technique the probe is guided to the optimum target at the most ventral pallidum and ansa lenticularis by macroelectrode stimulation of the internal capsule and optic tract from within the globus pallidus, with the thresholds providing a relative measure of the electrode proximity to these structures. We have characterized these localizing macroelectrode stimulation parameters in 57 posteroventral pallidotomies with consistent anatomic lesion placement, excellent outcome, and no complications.Using a 1.8 × 2.0 mm radiofrequency electrode for macroelectrode stimulation (RFG-3C, Radionics Inc.), minimum voltages (thresholds) to activate motor (at a frequency of 2 Hz) or visual (at a frequency of 100 Hz) responses as well as impedance measurements were obtained at the final target (Tf) and at distances proximal to Tf along the electrode trajectory. The visual and motor threshold voltages at Tf via our standard approach angles (50 ° above base plane, 20 ° from the sagittal plane), had a range of 1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that as the probe approaches Tf there is a significant decrease in voltage thresholds for motor (P<.0001) and visual (P<.0001) responses in an individual patient indicating that the probe is converging on these structures. Increases in impedance between Tf, 2–3 mm, and 4–5 mm proximal to Tf were also statistically significant (P<.0001). Microelectrode recording of electrophysiological neuronal activity at various points along the trajectory towards the target showed distinct firing patters providing identification of the globus pallidus externus and internus, ansa lenticularis, and optic tract.Macroelectrode electrophysiological stimulation within the target volume, inducing threshold responses in the internal capsule and optic tract, provides for accurate localization of the most effective PVP target in the ansa lenticularis. In unresponsive patients, the utilization of microelectrode recording for the identification of the pallidal borders and the optic tract improves safety.     

Persistent diarrhea and fecal shedding of retroviral nucleic acids in children infected with human immunodeficiency virus

Gastrointestinal dysfunction is a serious problem in many children infected with human immunodeficiency virus (HIV), the etiology of which has not been clearly defined. Quantitative nucleic acid amplification was used to study the correlation between shedding of HIV nucleic acids and gastrointestinal symptoms in HIV-infected infants and children. Many with HIV infection and persistent diarrheal disease shed HIV nucleic acids in their feces, as did an HIV-infected patient without apparent diarrheal disease. HIV nucleic acids were not found in feces of non-HIV-infected individuals. Intestinal infection with HIV appears to be important in the pathophysiology of gastrointestinal dysfunction in infants and children with HIV infection. Furthermore, the fecal shedding of HIV may play a role in HIV transmission in environments prone to high levels of fecal-oral contamination.     

带血管蒂岛状筋膜瓣移植治疗晚期类风湿性髋关节炎

目的：阐明带血管蒂岛状筋膜瓣移植治疗晚期类风湿性髋关节炎的疗效。材料和方法：对４２例４８髋晚期类风湿性髋关节炎病人采用以旋股外侧血管降支为蒂的股前外侧筋膜瓣移植行患髋成形术。结果：术后随访４～１０．５年，平均４．５年，髋关节活动范围术前平均１６．５°，术后２２８．６°，按照Ｃｈａｒｎｌｅｙ和吴之康人工髋关节置换术后的疗效评定标准，优良２９髋、很好１３髋、好６髋，尚可、差、很差无。结论：患者年龄在１５～４０岁之间为合适的治疗年龄。与人工髋关节置换术相比，本方法对髋关节正常结构破坏小；一旦手术失败仍可选用其它治疗方法弥补；且并发症少、费用低、远期效果好。     

喉癌患者染色体对致突变剂诱发畸变的敏感性研究

采用平阳霉素作为诱变剂，对２８例喉癌患者和２３例正常人做外周血淋巴细胞染色体对诱变剂敏感性研究，结果显示喉癌患者的染色体总畸变率、每细胞染色单体断裂率（ｂ／ｃ值）和细胞畸变率分别为１．９８％±０．０５％，０．５７％±０．３５％和４２．８％±１２％。正常人则分别为０．９４％±０．０４％，０．２８％±０．１２％和２７％±１２％。经统计学处理，喉癌患者组与正常人组的差异有高度显著性。并结合实验结果探讨了染色体对致突变剂的敏感性与患喉癌风险的关系。     

Electrocardiographic findings in children with Lyme disease.

The incidence of cardiac involvement in Lyme disease (LD) has been estimated to be 4 to 10% in adults, with conduction and rhythm disturbances noted most frequently. To assess the frequency of electrocardiographic abnormalities in children with LD, we prospectively performed 12-lead electrocardiograms in 32 randomly selected children presenting with LD between May and September 1989. No patient had symptoms of cardiac involvement. Using defined diagnostic criteria, combining symptoms, signs, serology, and residence in or travel to an endemic area, 14 patients were classified as having definite LD and 10 were categorized as probable. The incidence of electrocardiographic abnormalities in the definite group was 29% (4/14), including two patients with 1 degree atrioventricular block, one with left axis deviation, and one with ventricular ectopy. Thirty percent (3/10) of the probable group had abnormal ECGs, including one with ST-T wave abnormalities, one with prominent sinus arrhythmia, sinus bradycardia, and wandering atrial pacemaker, and one with ectopic atrial bradycardia. No patient required cardiac therapy. The incidence of abnormal ECG findings in this group of children with either probable or definite LD was thus 29%, with 1 degree atrioventricular block noted most frequently. When the diagnosis of LD is highly suspected, an electrocardiogram may be a useful screening test for cardiac involvement.