In vitro reversal MDR of human carcinoma cell line by an antisense oligodeoxynucleotide-doxorubicin conjugate.

A conjugate of antisense oligodeoxynucleotide (AS ODN) covalently linked with deoxorubicin (DOX) was synthesized. Its properties and antitumour activity in human carcinoma DOX resistant cells (KB-A-1) were investigated in vitro. The results showed that the conjugate was strongly stable both in Dulbecco's Phosphate-Buffered Saline (PBS) and in culture medium. The intracellular concentration of the conjugate was higher than that of the AS DON by HPLC analysis. The conjugate showed potent dose-dependent inhibition to the growth of KB-A-1 cells. Chemosensitivity of KB-A-1 cells to DOX was also investigated in vitro. When the cells were first exposed to the conjugate (0.5 microM) and then exposed to DOX for 24 h, the IC50 value of DOX decreased from 21.5 to 2.2 microM. In contrast, when treated with the mixture of the same concentration of the AS ODN with equivalent DOX, the IC50 value of DOX was 16.8 microM. Intracellular DOX concentration was detected in KB-A-1 treatment with the conjugate in vitro by HPLC. The results showed that the intracellular DOX concentration was 6.4-fold increased in KB-A-1 cells treated with the conjugate compared to treatment with DOX alone. In contrast, 1.8-fold increasing was observed when treated with the AS ODN. Western blot analysis showed a significantly decrease in the amount of P-glycoprotein in KB-A-1 cells. These results suggest that the conjugate is effective in reversing multidrug resistance. Certainly, further studies are conducting to explore the antitumour effect of the conjugate in vivo.     

Comparison of mortality risk associated with bacteremia due to methicillin-resistant and methicillin-susceptible Staphylococcus aureus.

OBJECTIVE: To quantify the clinical impact of methicillin-resistance in Staphylococcus aureus causing infection complicated by bacteremia in adult patients, while controlling for the severity of patients' underlying illnesses. DESIGN: Retrospective cohort study from October 1, 1995, through December 31, 2003. PATIENTS AND SETTING: A total of 438 patients with S. aureus infection complicated by bacteremia from a single Veterans Affairs healthcare system. RESULTS: We found that 193 (44%) of the 438 patients had methicillin-resistant S. aureus (MRSA) infection and 114 (26%) died of causes attributable to S. aureus infection within 90 days after the infection was identified. Patients with MRSA infection had a higher mortality risk, compared with patients with methicillin-susceptible S. aureus (MSSA) infections (relative risk, 1.7 [95% confidence interval, 1.3-2.4]; P<.01), except for patients with pneumonia (relative risk, 0.7 [95% confidence interval, 0.4-1.3]). Patients with MRSA infections were significantly older (P<.01), had more underlying diseases (P=.02), and were more likely to have severe sepsis in response to their infection (P<.01) compared with patients with MSSA bacteremia. Patients who died within 90 days after S. aureus infection was identified were significantly older (P<.01) and more likely to have severe sepsis (P<.01) and pneumonia (P=.01), compared with patients who survived. After adjusting for age as a confounder, comorbidities, and pneumonia as an effect modifier, S. aureus infection-related mortality remained significantly higher in patients with MRSA infection than in those with MSSA infection, among those without pneumonia (hazard ratio, 1.8 [95% confidence interval, 1.2-3.0]); P<.01. CONCLUSIONS: The results of this study suggest that patients with MRSA infections other than pneumonia have a higher mortality risk than patients with MSSA infections other than pneumonia, independent of the severity of patients' underlying illnesses.     

Steroid glaucoma: corticosteroid-induced ocular hypertension in cats.

This study was undertaken to develop a feline model of corticosteroid-induced ocular hypertension. In the first experiment, eight cats were selected whose intraocular pressure (17 +/- 0.4 mmHg) was consistently below the mean baseline intraocular pressure of our colony (24 +/- 0.5) during the preceding 2 months. Unilateral twice or thrice daily topical application of 10 microliters 1% dexamethasone sodium phosphate caused a gradual intraocular pressure increase that became significant (P less than 0.05) within 2-3 weeks. There was no significant change in body weight, but several eyes developed cataracts. Similar results were obtained with treatment of normotensive cat eyes with dexamethasone, or with 1.0% prednisolone acetate (PredForte) twice a day. Topical application of PGF2 alpha-1-isopropyl ester (0.1 or 0.25 microgram PG equivalent) to such steroid-treated eyes yielded significant intraocular pressure reduction and pupillary miosis, similar in magnitude to those exhibited by normal eyes. When dexamethasone treatment was reduced to once daily, after prolonged twice daily treatment, intraocular pressure decreased only slightly within 10 days. When dexamethasone treatment was stopped, intraocular pressure declined to normal levels within 6-7 days. These findings show that adult cat eyes develop steroid-induced ocular hypertension that is maintained and reversible. As opposed to previous findings on rabbits, steroid-induced feline ocular hypertension appears to be a good model for this clinical condition and may be suitable for the testing of potential glaucoma drugs.     

Effect of fathers'' age and birth order on occurrence of congenital heart disease.

STUDY OBJECTIVE--The aim was to examine if there is an effect of fathers' age and of birth order on the occurrence of congenital heart disease. DESIGN--This was a hospital based case-referent study including use of birth defects surveillance data. SUBJECTS--Subjects were 497 cases of congenital heart disease aged between 3 months and 5 years, born in Beijing and Hebei Province, China; 6222 children without congenital heart disease serve as reference baseline. MEASUREMENTS AND MAIN RESULTS--With stratified analysis and logistic regression analyses, congenital heart disease was found to be associated with fathers' age less than 25 years (odds ratio 2.63), independent of mothers' age and of birth order. There was also evidence to show a higher birth order effect on the occurrence of congenital heart disease independent of parental ages. CONCLUSION--Higher birth order and fathers aged less than 25 years were both independently associated with some categories of congenital heart disease and with congenital heart disease overall.     

双侧声带麻痹及固定的治疗：附12例报告

文中总结了１２例双侧声带麻痹或固定的治疗。气道通畅型２例，行病因治疗。气道阻塞型１０例，８例作了气管切开术，声带外移术３例，２例呼吸发音功能恢复较好，１例失败者行一侧声带切除＋喉扩张术。另外２例行Ｔ型管扩张术，均顺利拔管。药物治疗共５例。并讨论各种手术治疗现状。     

散发性急性戊型肝炎血清抗体动态变化和肝脏超微…

为探讨散发性戊型肝为血清抗体动态变化，应用酶联免疫法（ＥＩＡ）检测了７例急性戊型肝炎抗戊型肝炎病毒（ＨＥＶ）ＩｇＧ和ＩｇＭ抗体、并对１例２进行了肝超微结构病理检测，结果表明，发病１０天至４５天内抗ＨＥＶ－ＩｇＧ和ＩｇＭ滴度最高，发病第４０天仍有肝细胞肿胀，胞浆空化和线粒体固缩等病理变化。患者轿清抗－ＨＥＶＩｇＭ滴度在４５天后逐渐下降，２个月内全中消失，抗－ＨＥＶＩｇＭ滴度在４５天后逐渐下降，２个月     

列车乘务员SCL—90评定结果分析

采用ＳＣＬ—９０症状自评量表对某铁路分局４６７名列车乘务员的心理卫生状况进行了分析。结果显示总均分、阳性症状均分、阳性项目数、九组症候群因子分、达到或超过中等严重程度的发生频数均显著高于对照组。经多元逐步回归分析,仅细菌总数和二氧化碳对列车乘务员心理卫生状况有一定影响,其原因多与工作环境的不良因素和工作性质有关。     

Effects of topical epinephrine on aqueous humor dynamics in the cat

The purpose of this study was to investigate, in cats, the effects of topical epinephrine on aqueous humor dynamics as measured by the non-invasive method of fluorophotometry and by other methods. Measurements were carried out on 12 cats before and after one week of twice daily treatment with 2% epinephrine hydrochloride to one eye. Aqueous flow and outflow facility were determined using fluorophotometry. Uveoscleral outflow was calculated from these results and was evaluated with anterior chamber perfusion of FITC-dextran. Outflow facility also was measured by tonography. Epinephrine-treated eyes, compared with their baseline values, showed a 31% reduction in intraocular pressure (P<0.001), a 23% reduction in aqueous flow (P<0.05), a 60% increase in fluorophotometric outflow facility (P<0.05), and a 43% increase in tonographic outflow facility (P<0.05). Treated eyes, compared with contralateral control eyes, showed a 27% reduction in IOP (P<0.005), a 25% reduction in aqueous flow (P<0.005), a 38% increase in fluorophotometric outflow facility (P<0.05), and a 34% increase in tonographic outflow facility. When evaluated by both fluorophotometry and FITC-dextran tracer methods, epinephrine had no significant effect on uveoscleral outflow. It was concluded that, in cats treated with topical epinephrine twice daily for a week, a reduction in intraocular pressure is induced by an increase in outflow facility and decrease in aqueous flow.