Identification of cytotoxic principles from Fusarium avenaceum using bioassay-guided fractionation

The cytotoxicity of extracts from rice cultures of five Fusarium avenaceum strains against the porcine epithelial kidney cell-line PK-15 was investigated using the Alamar Blue™ assay. After the identification of known fungal metabolites, cytotoxic extracts were fractionated using semi-preparative reversed-phase HPLC and normal phase LC, and the fractions were tested for cytotoxicity. In this way, two different groups of metabolites were identified as the major cytotoxic principles of the extracts. High concentrations of enniatins, especially enniatins B and B1, inhibited the metabolic activity of PK-15 cells. Furthermore, an unidentified metabolite, produced in high amounts by a strain that produced relatively small amounts of enniatins, was also found to be cytotoxic to PK-15 cells. This study shows that enniatins, a group of cyclic depsipeptides, which have been ignored as significant contributors to the toxicity of fungal extracts, may account for most of the observed effect for F. avenaceum.     

Effect of pentoxifylline on veno-occlusive priapism-induced corporeal tissule lipid peroxidation in a rat model

Objective: To investigate whether pentoxifylline could play a role in attenuation of the hazardous effects of ischemia/reperfusion on corporeal tissue in a rat model of veno-occlusive priapism (VOP). Materials and methods: Placebo and pentoxifylline were given to eight groups of rats prior to priapism being induced by a vacuum constrictive device for durations of 6 and 12 h, respectively. Half of the groups of rats that underwent the same duration of priapism (ischemic) were subjected to 1 h of detumescence after band removal (reperfusion). One group underwent no manipulation and no drug administration and served as a baseline determination (control). Corporeal homogenates were examined for lipid peroxidation (LP) derived malondialdehyde (MDA) accumulation via thiobarbituric acid assay. Results: MDA concentration differed significantly between VOP rats and controls (P < 0.001) but did not differ significantly between ischemic-only groups and reperfused groups (P > 0.05). In the pentoxifyllinepretreated groups, although MDA accumulation tended to be slightly lower than in the placebo groups, the difference was not statistically significant (P > 0.05) either in the 6- or 12-h duration priapic groups. Conclusions: LP, an indicator of radical oxygen metabolite (ROM) induced injury, occurs in rat corporeal tissue during and after abolishment of VOP. Single-dose pentoxifylline pretreatment failed to exert a protective effect on corporeal tissue in a rat model of VOP in terms of attenuation of LP.     

乳腺癌的二级预防

在我国乳腺癌的发病率有逐渐增加的趋势，而且它对我国中年妇女的威胁最大。乳腺癌二级预防已被公认是降低死亡率的有效途径。综合应用宣教、自检、体检、Ｘ线摄影、近红外线摄影、超声检查、针吸活检、手术活检等方法对年龄在３０～６０岁的城市妇女定期进行分层筛检、监检可以使乳腺癌患者早期被发现，降低乳腺癌死亡率。     

Danish version of the Oswestry disability index for patients with low back pain. Part 2: Sensitivity, specificity and clinically significant improvement in two low back pain populations

In studies evaluating the efficacy of clinical interventions, it is of paramount importance that the functional outcome measures are responsive to clinically relevant change. Knowledge thereof is in fact essential for the choice of instrument in clinical trials and for clinical decision-making. This article endeavours to investigate the sensitivity, specificity and clinically significant improvement (responsiveness) of the Danish version of the Oswestry disability index (ODI) in two back pain populations. Two hundred and thirty three patients with low back pain (LBP) and/or leg pain completed a questionnaire booklet at baseline and 8 weeks follow-up. Half of the patients were seen in the primary (PrS) and half in the secondary sectors (SeS) of the Danish Health Care System. The booklet contained the Danish version of the ODI, along with the Roland Morris Questionnaire, the LBP Rating Scale, the SF36 (physical function and bodily pain scales) and a global pain rating. At follow-up, a 7-point transition question (TQ) of patient perceived change and a numeric rating scale relating to the importance of the change were included. Responsiveness was operationalised using three strategies: change scores, standardised response means (SRM) and receiver operating characteristic (ROC) analyses. All methods revealed acceptable responsiveness of the ODI in the two patient populations which was comparable to the external instruments. SRM of the ODI change scores at 2 months follow-up was 1.0 for PrS patients and 0.3 for SeS (raw and percentage). A minimum clinically important change (MCID) from baseline score was established at 9 points (71%) for PrS patients and 8 points (27%) for SeS patients using ROC analyses. This was dependable on the baseline entry score with the MCID increasing with 5 points for every 10 points increase in the baseline score. We conclude that the Danish version of the ODI has comparable responsiveness to other commonly used functional status measures and is appropriate for use in low back pain patients receiving conservative care in both the primary and secondary sector.     

Secondary reconstruction of the short philtrum in the bilateral cleft deformity

Summary This technique for reconstruction of the short philtrum requires an understanding of the viscoelastic properties of the skin and how to use these to increase skin dimensions. This is combined with contouring and splinting with a subcutaneous cartilage graft. Three representative cases are presented to illustrate the method to achieve an aesthetically acceptable lip and its long-term follow-up. No complications have been encountered using this over a 15-year period. The technique can be combined with other secondary reconstructive procedures on the lip and palate. Work completed at: Providence Hospital, 16001 West Nine Mile Road, P.O. Box 2043, Southfield, Michigan 48037, USA     

A new method for the correction of secondary unilateral cleft lip nose

Summary In 1982, Dibbell described a procedure to correct this distortion by rotating and advancing the nostril medially and superiorly. We used this method in our department for several years, but as Dibbell himself experienced, we didn't always obtain satisfactory results. Like many authors, I agree that the best approach for proper correction of the secondary unilateral cleft lip nose deformity is the external approach using transcolumellar incisions, because the lower lateral cartilage exposure is inadequate with Dibbell's method. I added the transcolumellar incision similar to Bardach's to solve this problem. In this paper, this combination technique will be presented and contrasted with Dibbell's and Bardach's techniques.     

Tacrolimus metabolite cross-reactivity in different tacrolimus assays

Objectives: Tacrolimus (FK506) is an immunosuppressive drug with great clinical promise. There is a controversy regarding the role of tacrolimus metabolites in immunosuppression and toxicity, and immunoassays and immunophilin binding assays have not been adequately tested for metabolite cross-reactivity. Methods are limited to HPLC and HPLC-MS for quantifying the parent drug. Mixed lymphocyte culture assay (MLC) is the preferred functional bioassay for the measurement of parent drug and active metabolites but it is not practical for routine laboratory use. Due to differences in assay methods and reagent specificity, the concentration of tacrolimus in a given specimen may vary among different assay kit manufacturers. The objective of this study was to evaluate the degree of cross-reactivity or interference of the three first-generation tacrolimus metabolites [13-O-demethyl (M-I), 31-O-demethyl (M-II) and 15-O-demethyl (M-III)] among two different tacrolimus immunoassays (Immunoassay: PRO-Trac II FK506, Abbott IMx tacrolimus-II); and the radioreceptor assays (RRA) using minor immunophilins (14, 37, and 52 kDa immunophilins) and tacrolimus binding protein (FKBP12).

Methods: First-generation tacrolimus metabolites (M-I, M-II, and M-III) spiked in drug-free whole blood were assayed with RRA using three minor immunophilins (14, 37, and 52 kDa) and two commercial immunoassay procedures (Incstar PRO-Trac II tacrolimus, Abbott IMx tacrolimus II). The results were compared to previously published FKBP-12 RRA data and their immunosuppressive potency.

Results and conclusion: The first generation tacrolimus metabolites (M-I, M-II, and M-III) were tested using concentrations of 10 and 20 ng/mL. The significance of the metabolite interference (% of the total interference) was calculated based on the relative concentration of each metabolite present at steady-state trough concentrations in renal transplant recipients [22]. Metabolite I, which has no functional immunosuppressive activity showed minimal interference compared to M-II and M-III in all assays except the 14 kDa RRA. The Incstar PRO-Trac II tacrolimus assay showed the least M-I interference. Metabolite-II, which has a pharmacologic potency similar to the parent drug, showed a significant interference in the immunoassays and significant interference in radioreceptor assays. Metabolite III, which is pharmacologically inactive, produces 3–10% interference in the different assays if its presence in the blood is 6% of the parent drug. The total interference from these three metabolites was greater in the immunoassays than in the receptor assays. Receptor assays for tacrolimus provide results closer to the target value than do immunoassays.     

中效人胰岛素联合瑞格列奈治疗磺脲类降糖药继发性失效临床观察

目的观察中效人胰岛素与瑞格列奈联合应用治疗磺脲类降糖药继发性失效的疗效。方法将磺脲类降糖药继发性失效(SFS)36例病例随机分成两组,分别接受睡前小剂量中效人胰岛素加瑞格列奈(A组,20例)和单纯瑞格列奈(B组,16例)治疗,比较两组各生化指标。结果①治疗前空腹血糖(FPG)、餐后2小时血糖(2hPG)、C肽(C-P)、糖化血红蛋白(HbA1c)水平两组间无统计学差异;②治疗3个月后两组自身的FPG、2hPG、C-P、HbA1c水平均较治疗前明显改善,P值分别为0.01、0.05、0.05、0.01;③治疗3个月后FPG、2hPG、C-P、HbA1c水平A组均低于B组,P值分别<0.01、0.05、0.05、0.01。结论中效人胰岛素联合瑞格列奈和单用瑞格列奈治疗磺脲类降糖药继发性失效均有疗效,胰岛素和瑞格列奈联用优于单用瑞格列奈。     

脑卒中与继发性癫癎

目的:探讨首发脑卒中患者继发性癫癎的发病率、发病时间与脑卒中病变部位的关系。方法:回顾性分析经我院近3年来治疗的659例首发脑卒中住院患者的临床资料。结果:首发脑卒中患者继发癫癎发生率为8.19%(54/659)。癫癎发作与卒中病变部位有关,累及皮层或邻近皮层者易继发癫癎(53.33%,24/45)。54例继发癫癎中68.52%为早发性癫癎(起病后2周内),余31.48%为晚发性癫癎(起病2周以后)。以脑出血继发早发性癫癎为主(81.25%,13/16);脑梗死则易发生晚发性癫癎(60.00%,12/20)。结论:分析首发卒中后癫癎的发病特点有助于指导临床治疗。     

外伤性白内障术后二期人工晶状体植入术

目的 探讨外伤性白内障术后二期植入后房型人工晶状体的时机和手术方式。方法 对34例(34只眼)外伤性白内障术后无晶状体眼根据不同情况采用直接睫状沟植入法或缝线固定法进行二期植入后房型人工晶状体，观察两组患者的术后反应和治疗效果。结果 直接睫状沟植入法14只眼(41．2％)，缝线固定法20只眼(58．8％)，31只眼(91．2％)视力达到0．1以上，21只眼(61．76％)视力达0．3以上，28只眼(82．4％)术后矫正视力等于或高于术前最佳矫正视力。结论 选取合适的时机和方式二期植入人工晶状体，有助于减少术后并发症，提高视功能的恢复。