Effects of cigarette smoking and age on the maturation of human oocytes

We investigated whether cigarette smoking, measured by follicular fluid concentrations of cotinine (a major metabolite of nicotine), affects the maturity of oocytes from women undergoing in-vitro fertilization (IVF) and embryo transfer. In 234 women, follicular fluid samples were assessed for cotinine and their 2020 oocytes were assessed for maturity stage. Data on individual proportions of oocytes which were mature (OM) and were fertilized (OF) were analysed by regression in relation to age and follicular fluid cotinine. OF gave an independent assessment of oocyte maturity. Both age and follicular fluid cotinine entered the OM and OF regressions and were significant. The age-adjusted regression coefficients for log cotinine were positive; greater cotinine concentrations usually accompanied greater OM and OF. The cotinine effect on OM was positive in younger women, but it became negative (decreased OM with increasing cotinine concentrations) in older women (> or = 40 years). We further found in older women an average reduction of approximately 50% in the number of mature oocytes; this reduced number was lower than the number of embryos usually transferred. Smoking can reduce the number of mature oocytes even further, therefore risking a negative IVF-embryo transfer outcome. This may be the reason why the negative effects of smoking become clinically detectable in older women.      

Prognostic significance of HIV-associated oral lesions and their relation to therapy

The oral manifestations of HIV infection have been considered to be of value in assessing disease progression in the developed world. However, the potential use of oral lesions as prognostic markers in resource-poor countries has yet to be fully investigated. There is reasonably compelling evidence in the developed world for an association between oral lesions and viral load. However, the true nature of this association is less clear and there are few data available from the developing world. With the introduction of HAART, a change in prevalence of the oral manifestations of HIV infection has been observed, including regression of oral candidiasis, Kaposi's sarcoma and oral hairy leukoplakia. However, oral condylomata and herpes simplex virus infection appear to persist with HMRT therapy. Further research in partnership with resource-poor countries is required to document disease progression and the associated oral lesions in both adults and children.     

Determination of adhesion force between single cell pairs generated by activated GpIIb-IIIa receptors

A biophysical approach was used to directly determine the avidity of the junction between two Chinese hamster ovary (CHO) cells bearing recombinant GpIIb-IIIa in the presence and absence of fibrinogen. Micromanipulation was used to induce conjugation of the cell pairs with or without activating the GpIIb-IIIa molecules with monoclonal antibody (MoAb) 62. Activation of GpIIb-IIIa caused an increase in the force required to separate the conjugates. The molecular bonding force between cells bearing activated GpIIb-IIIa and fibrinogen molecules was found to be 2.1 x 10(-7) dyne, which is 3.7 times higher than that between nonactivated GpIIb-IIIa and fibrinogen (5.7 x 10(-8) dyne). The results provide a quantitative assessment of the molecular bonding force between fibrinogen and the GpIIb-IIIa expressed on cell surface. The findings indicate that the activation of GpIIb-IIIa leads to an increase in the adhesive force in CHO cell aggregation by increasing the strength of the GpIIb-IIIa-fibrinogen bonds rather than the number of these bonds.     

补肺健脾益肾方治疗对老年COPD稳定期患者T淋巴细胞亚群、BODE指数及生活质量的影响

目的:评价补肺健脾益肾方治疗老年慢性阻塞性肺疾病(COPD)稳定期的疗效及对患者外周血T淋巴细胞亚群、BODE指数及生活质量的影响.方法:将80例中医辨证为肺脾肾气虚型COPD稳定期患者随机分组,对照组(40例)仅采取常规西医治疗,而观察组(40例)在常规西医治疗的基础上联合补肺健脾益肾汤,治疗8周后比较临床疗效及患者外周血T淋巴细胞亚群、BODE指数及生活质量的变化.结果:经治疗后观察组BODE指数及BMI积分、FEV1积分、MMRC积分、6MWT积分均较对照组明显减少,差异具有统计学意义(P＜0.05);经治疗后观察组CD3+、CD4+及CD4+/CD8+较对照组明显升高,CD8 +水平较对照组明显降低,差异具有统计学意义(P＜0.05);两组经治疗后肺功能指标FEV1和FEV1/FVC均较治疗前有明显改善,差异具有统计学意义(P＜0.05);两组治疗后SGRQ评分均较治疗前明显降低,但观察组治疗后SGRQ评分明显低于对照组,差异具有统计学意义(P＜0.05).结论:补肺健脾益肾方用于老年COPD稳定期治疗可改善患者肺功能及BODE指数,提高生活质量,增强细胞免疫功能.     

Management of oral complications of disease-modifying drugs in rheumatoid arthritis

Stomatitis is a troublesome adverse effect of disease-modifying anti- rheumatic drug (DMARD) therapy in rheumatoid arthritis (RA) patients. This review presents data to examine the incidence, clinical features and consequences of DMARD-related stomatitis, and suggests an algorithm for its clinical management. The specific objectives of the two studies presented here were to determine the incidence of DMARD-related stomatitis and its effect on DMARD continuation, and secondly to identify the clinical and laboratory risk factors. We investigated two cohorts of patients: (i) a retrospective survey of data collected from drug monitoring clinics run for patients on DMARDs from 1987 to 1994 involving 1539 patients and 2394 drug exposures; (ii) a prospective study of 25 consecutive RA patients presenting with DMARD-related stomatitis compared to 29 RA controls with no history of DMARD stomatitis. The retrospective survey showed that 2% of DMARD patients stopped therapy because of stomatitis, but 55% of these were able to resume the same therapy. In the case control study. 24% of patients discontinued temporarily and 8% permanently. Cases of DMARD-related stomatitis differed from controls in that they had a higher incidence of previous mouth ulcers (40% vs 14%), they smoked less (8% vs 31%) and Schirmer's test was more often abnormal (44% vs 21%). There were no differences in RA severity, disease activity or oral hygiene. Haematinic deficiencies were equally common in cases and controls: 30% for iron, 8% for vitamin B12 and 24% for folic acid. Herpes simplex virus was involved in a minority (8%) of cases. In conclusion, the occurrence of stomatitis in RA patients on DMARD should not lead to cessation of drug therapy, but to a careful evaluation so that patients may be maintained on effective treatment.      

Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bons marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.