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.     

Influence of blood supply of the esophageal and gastric stumps on anastomotic healing after esophagogastrostomy in rabbits]

OBJECTIVE: To study how blood supply of the esophageal and gastric stumps influences the anastomotic healing after esophagogastrostomy in rabbits. METHODS: Twenty-seven New Zealand rabbits were randomly divided into 3 groups to receive esophagogastrostomy, followed by different procedures. Except for those in group I, all the rabbits were subjected to procedures of reducing the blood supply either of the esophageal or the gastric stump (group II and group III, respectively), followed by single-layer esophagogastric anastomoses using interrupted 5-0 polypropylene sutures. Ten days after operation, all the rats were killed and the anastomotic sites excised for measurement of the inner diameter, tensile strength, and hydroxyproline concentration. RESULTS: Healing of the esophagograstric anastomosis was obtained in all the rabbits but one with anastomotic leakage in group I and one with perforation of the gastric fundus in group III. The anastomotic inner diameters were similar in all the three groups, whereas the tensile strength and hydroxyproline concentration at the anastomoses decreased in group III in comparison with the other two groups (P<0.05) that had similar measurements (P>0.05). CONCLUSIONS: Extended length of the free esophageal stump does not significantly affect anastomotic healing as decrease of blood supply in the gastric stump.     

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.     

乳腺囊性增生病癌变过程中部分因素变化的意义

检测乳腺囊性增生病（ＦＣＤ）经不典型增生到癌变部分因素的变化。结果提示：从因明显ＦＣＤ症状活检至癌变为２～１０年；从Ⅱ级以上不典型增生到临床癌变需２～７年；癌变率为３．１％。ＦＣＤ患者存在性激素分泌调控失常，血浆雌激素和催乳素含量增加，导致上皮细胞增生。乳腺一般性增生细胞的ＤＮＡ含量和超微结构与正常乳腺上皮细胞相似；无肿瘤相关抗原及异常基因产物表达。而发生在一般性增生基础上的不典型增生则呈现细胞基因物质ＤＮＡ含量增加，部分为超４Ｃ的多倍体细胞；同时出现细胞膜和细胞核超微结构异常；雌激素受体含量增加，对性激素的依赖性和敏感性增强；部分不典型增生细胞出现胚胎性肿瘤相关抗原和异常基因产物表达。随不典型增生程度加重至乳腺癌，上述诸因素的变化趋势具有明显规律性。提示ＦＣＤ上皮细胞从一般性增生经不典型增生至乳腺癌为细胞生物学连续逐渐变化的过程。部分不典型增生细胞中具有癌倾向的细胞生物学行为异常和表型变化与乳腺癌发生密切相关。细胞核ＤＮＡ含量等异常变化及程度可作为乳腺癌前病变发展程度的客观标志     

A comparative study on therapeutic method of traumatic epidural hematoma

Objective： To explore the therapeutic methods, surgical indications and clinical practice of minimally invasive surgery on traumatic epidural hematoma （EDH）. Methods： Retrospective study was made on 135 patients with traumatic EDH admitted into our hospital from June 2002 to August 2005. Sixty-five patients were treated with mini-invasive negative pressure drainage （treatment group）, 70 patients with comparable condition used traditional craniotomy （control group ）. The mean time of operation, average days in hospital, expenditure and prognosis of two groups were recorded and analyzed. Results： There was no significant difference in therapeutic efficacy between two groups. Patients in treatment group had a shorter hospital stay and less expenditure than those in control group. Conclusion： Mini-invasive negative pressure drainage is simple, effective, economical and applicable to some traumatic EDH patients.     

人工家蚕蛹巴西虫草的毒性研究

对人工家蚕蛹巴西虫草的毒性进行了研究。结果表明：小鼠和大鼠经口ＬＤ５０分别为＞４３．０ｇ／ｋｇ和＞５０ｇ／ｋｇ。３０天喂养试验中大鼠食欲下降，体重增长减慢；血清胆固醇和血清尿素氮浓度降低，血清总蛋白和血糖无改变；血尿常规无异常；心、肝、牌等脏器系数无改变；肝、肾组织病理学检查未发现明显改变。可认为该产品无明显急性和亚急性毒性。