美国口腔医学院的社区教学模式

高昂的医疗费用和不够便利的就医条件是阻碍美国人,特别是少数民族和劣势群体,获得口腔医疗护理的重要原因,其根源在于传统口腔教学僵化的教学方式和昂贵的学习费用.近年来,美国各界为改变口腔医疗的状况,进行了多种尝试,旨在降低口腔医学学习成本,并培养乐于奉献、积极投身社区医疗的口腔医师.该文分析了美同口腔医疗面临的问题及其原因,并以亚利桑那大学齿科与口腔健康学院的教学改革为例,介绍美国口腔医学教学如何与社区医疗相结合.     

Pharmacokinetic parameters of nevirapine and efavirenz in relation to antiretroviral efficacy

Optimal adherence is essential for successful antiretroviral therapy. We analyzed the relation between minimum plasma drug concentration (Cmin) and total drug exposure over 24 hr (AUC24) with virologic failure for therapy-adherent patients in the nevirapine (NVP) and efavirenz (EFV) groups of the double nonnucleoside study (2NN), which compared the efficacy of NVP and/or EFV together with stavudine and lamivudine. The objective was to find cutoff values of the Cmin and AUC24 below which the risk of virologic failure increased. The relation between Cmin and AUC24 with virologic failure (never a plasma viral load [pVL] < 50 copies/ml or a rebound to two consecutive pVL > 50 copies/ml) was analyzed with proportional hazard analyses. Data were censored at end of study or change of allocated treatment. The risk of virologic failure with NVP (n = 511) started to increase at a Cmin < 3.1 mg/L (hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.89-1.97), but there was no cutoff value below which a statistically significant increased risk occurred. Neither was such a cutoff point identified for the AUC24. The risk of virologic failure with EFV (n = 312) was significantly increased at a Cmin < 1.1 mg/L (HR, 1.95; 95% CI, 1.08-3.54) and an AUC24 < 40 mg x hr x L1 (HR, 1.95; 95% CI, 1.07-3.54). Both cutoff values represent the median values for adherent patients. These associations were driven by patients from Thailand. Adjusting for geographical region made the association between Cmin and AUC24 with virologic failure statistically nonsignificant. The sensitivity of the Cmin values was too low (29% for NVP, 64% for EFV) to be an adequate predictor for virologic failure. We conclude that identifying the Cmin value for the sole purpose of predicting virologic failure in patients who report to be adherent to NVP or EFV is questionable because of the absence of a concentration-response relation (NVP) or the low sensitivity for such a cutoff value (NVP and EFV).     

地龙(蚯蚓)体内磷脂的组成和血小板活化因子的生物合成

首次发现低等动物地龙(Eisenia foetida,亦称蝗蚓)体内含有血小板活化因子(PAF),含量随季节变化,平均达10.7±6.1pmol/g湿重(或1.1±0.5μmol/mol磷脂)。磷脂成分中,PAF前体物质1-O-烷基-2-酰基(长链)-sn-甘油-3-磷酸胆碱占磷脂酰胆碱的比例高达61.4%。并证实地龙体内含有与哺乳类动物相同的两种PAF合成酶蛋白。当针刺、切断等伤害性刺激时,PAF水平显著升高。此结果提示PAF是一种初始的活性介质,在地龙这类低等动物体内也参与机体的病理、生理应急反应。本研究为阐明中药地龙的降血压等药理作用机理提供新线索。     

The sulfide metabolite of sulindac prevents tumors and restores enterocyte apoptosis in a murine model of familial adenomatous polyposis

Sulindac, a non-steroidal anti-inflammatory drug (NSAID), is effective in treating intestinal adenomas in humans with Familial Adenomatous Polyposis (FAP) and in preventing intestinal tumors in the C57Bl/6J- Min+ (Min) mouse, an animal model of FAP. Sulindac is a prodrug metabolized by the liver and intestinal flora to a sulfone, which has no anti-inflammatory activity, and a sulfide, which is the active anti- inflammatory metabolite. In this study, we determined which of these metabolites is responsible for the anti-tumor effect of sulindac in Min mice. Min mice were treated with either sulindac sulfone or sulindac sulfide (0.5 +/- 0.1 mg/day). Min mice and homozygous C57Bl/6J-(+/+) normal litter-mates lacking the Apc mutation (+/+) were used as controls. At 110 days of age, all mice were euthanized and their intestinal tracts examined. Control Min mice had 33.2 +/- 6.6 tumors per mouse compared to 0.6 +/- 0.3 tumors for sulindac sulfide-treated Min mice (P < 0.001) and 21.9 +/- 4.5 tumors per mouse for sulindac sulfone-treated Min mice (P > 0.05). Decreased enterocyte apoptosis was observed in Min control mice and Min mice treated with sulindac sulfone. Sulindac sulfide restored to normal the level of apoptosis in the mucosa of Min animals and decreased levels of PGE2 in the small intestine of treated Min animals by 59% (P < 0.001). These data suggest that the anti-tumor effect of sulindac in Apc-deficient animals is mediated by the sulfide metabolite and correlates with suppression of tissue prostaglandin synthesis.      

Quality of life in patients treated with first-line antiretroviral therapy containing nevirapine and/or efavirenz

OBJECTIVE: To assess whether differences in safety profiles between nevirapine (NVP) and efavirenz (EFV), as observed in the 2NN study, translated into differences in 'health related quality of life' (HRQoL). DESIGN: A sub-study of the 2NN study, with antiretroviral-naive patients randomly allocated to NVP (once or twice daily), EFV or NVP+EFV, in addition to stavudine and lamivudine. METHODS: Comparing differences in changes of HRQoL over 48 weeks as measured with the Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire, using analysis of variance. RESULTS: The 2NN study enrolled 1216 patients. No validated questionnaires were available for 244 patients, and 55 patients had no HRQoL data at all, leaving 917 patients eligible for this sub-study. A total of 471 (51%) had HRQoL measurements both at baseline and week 48. The majority (69%) of patients without HRQoL measurements did, however, complete the study. The change in the physical health score (PHS) was 3.9 for NVP, 3.4 for EFV and 2.4 for NVP+EFV (P=0.712). For the mental health score (MHS) these values were 6.1, 7.0 and 3.9, respectively (P=0.098). A baseline plasma HIV-1 RNA concentration (pVL) > or = 100,000 copies/ml and a decline in pVL (per log10) were independently associated with an increase of PHS. An increase of MHS was only associated with pVL decline. Patients experiencing an adverse event during follow-up had a comparable change in PHS but a significantly smaller change in MHS, compared with those without an adverse event. CONCLUSIONS: First-line ART containing NVP and/or EFV leads to an improvement in HRQoL. The gain in HRQoL was similar for NVP and EFV, but slightly lower for the combination of these drugs.     

Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study

OBJECTIVE: The aim of this 2NN pharmacokinetic substudy was to investigate the population pharmacokinetics of nevirapine and efavirenz. METHODS: Treatment-naive, HIV-1-infected patients received nevirapine (once or twice daily), efavirenz or a combination with lamivudine and stavudine. Blood samples were collected on day 3 and weeks 1, 2, 4, 24 and 48. Using non-linear mixed effects modelling, pharmacokinetics of nevirapine and efavirenz and factors involved in the inter-individual variability were investigated. RESULTS: Clearance of nevirapine in the induction phase (<14 days) and at steady state (>28 days) were 2.02 I/h and 2.81 I/h, respectively. Volume of distribution and absorption rate constant were 77.0 l and 1.66 h(-1), respectively. Clearance of nevirapine was lower in females (13.8%) and in patients with hepatitis B (19.5%). Patients from South America and Western countries had higher clearance of nevirapine compared with Thai and South African patients. The clearances of efavirenz in the induction phase and at steady state were 7.95 l/h and 8.82 l/h, respectively. The volume of distribution and absorption rate constant were 4181 and 0.287 h(-1), respectively. Concomitant use of nevirapine increased clearance of efavirenz (43%). Patients from Thailand had lower clearance than the rest of the population. CONCLUSIONS: The population pharmacokinetics of nevirapine and efavirenz were assessed in the 2NN trial. For both drugs, an induction phase was distinguished from the steady-state phase. Gender, hepatitis B and geographical region were involved in the variability of the pharmacokinetics of nevirapine. Region and concomitantly used nevirapine were determinants of the pharmacokinetics of efavirenz.     

Evaluation of the local effect of cryosurgery in recurrent endometrial hyperplasia

A complex examination of the endometrium by cytomorphological methods, including impulse cytophotometry, radiometric monitoring and blood plasma-estradiol measurements was carried out in patients aged 41-54, to ascertain the local effect of cryosurgery performed for recurrent endometrial hyperplasia. The study was conducted in perimenopausal patients before and 4 months after cryosurgery. The results confirmed the high local effect of the treatment and showed DNA-histograms of the endometrium to provide a means of objective monitoring of treatment effectiveness.     

EGF促进RPE细胞β2肾上腺能受体诱导的cAMP形成：受体间交互作用分析

研究证实表皮生长因子(EGF)不影响培养人眼视网膜色常上皮(RPE)细胞cAMP的基础水平，但促进异丙肾上腺索激活β₂受体后诱导cAMP水平升高的效应，井呈量效信赖关系。EGF对腺嘌呤核苷A₂受体激动剂NECA诱导cAMP水子升高的效应没有明显影响．细胞增殖分析表明，EGF刺激人眼RPE细胞增殖，而DibutyrylcAMP和异丙肾上腺素抑制RGF刺激增殖的效应。结果提示，在人眼RPE细胞EGF和β₂受体之间存在受体间交互作用． （中华眼底病杂志，1995，11：25-27）