干细胞移植治疗时间窗与临床疗效的荟萃分析

目的:探讨寻找干细胞移植治疗急性心肌梗死的最佳移植治疗时间,指导临床应用,提高临床疗效。方法:应用计算机检索medline2000-01/2006-05文章,检索词为:"stem cell transplantation and/or acute myocardialinfarction(AMI)and/or chronic heart failure or ischemic cardiomyopathy",限定文章语言种类为English;同时计算机检索中国期刊全文数据库,相同时间的文章,检索词:"干细胞移植治疗,干细胞移植与急性心肌梗死,干细胞移植治疗与心力衰竭或慢性缺血性心肌病",限定文章语言种类为中文。共检索到300余篇与主题有关的文献,其中12篇有价值的文章见参考文献。移植时间取平均值,并按射血分数值和P值进行列表、作图。对干细胞移植时间与射血分数值之间的关系进行分析。结果:在急性心肌梗死后2～5d和9d以后进行干细胞移植治疗疗效较24h内及6～8d为好。结论:干细胞移植治疗急性心肌梗死的移植时间与临床疗效之间可能存在一定的相关性。经冠脉注入干细胞比经静脉或经心内膜下注入可以更好地改善左室功能,但还需要进一步的临床资料证实。     

Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Bilateral non-union of high tibial osteotomies treated by total knee arthroplasty: a case report

Non-union following high tibial osteotomy (HTO) is very uncommon. We present a case of bilateral non-union of HTOs with end-stage knee arthritis treated with staged, bilateral, posterior stabilized knee replacements. A 77-year-old female presented to our clinic with complaints of debilitating knee pain. She used a frame to get about in her home, she was unable to get up stairs, and she rarely went outside. Simple radiographs revealed bilateral non-unions of her osteotomies, subluxation of the tibial plateauxs and severe knee osteoarthritis. At the time of surgery, the non-unions were found to be fibrous stable. We took a minimal tibial plateaux resection and used long stem tibial stems with offset couplers to bypass the non-unions. At minimum 1 year follow-up, she was walking pain free with full knee range of motion. We found that primary total knee replacement (TKR) using tibial stems and without treating the tibial non-union gave satisfactory results.     

Activation of Human Neutrophils with Chemotactic Peptide, Opsonized Zymosan and the Calcium Ionophore A23187, But Not with a Phorbol Ester, is Accompanied by Efflux and Store-Operated Influx of Calcium

The objective of this study was to monitor alterations in cellular Ca²⁺ metabolism following activation of neutrophils with receptor(chemotactic peptide, FMLP, 1 M; opsonized zymosan, OZ, 0.5 mg/ml) and non-receptor (calcium ionophore, A23187, 1 M; phorbol 12-myristate 13-acetate, PMA, 25 ng/ml)-mediated stimuli of the pro-inflammatory functions of these cells. Ca²⁺ fluxes in activated neutrophils were measured using a fura-2-based spectrofluorimetric method in combination with radiometric (⁴⁵Ca) procedures which facilitate distinction between net efflux and net influx of the cation. Exposure of neutrophils to receptor-mediated stimuli and to A23187 was associated with an abrupt increase in cytosolic Ca²⁺ coincident with a rapid efflux of the cation which terminated at around 30 s. In the case of FMLP and OZ, this was followed by a delayed (30–60 s), store-operated influx of Ca²⁺, which was complete at around 5 min after addition of the stimulus. With A23187, however, influx of Ca²⁺ occurred immediately following activation of the cells. There were no detectable alterations in cytosolic Ca²⁺ or measurable net efflux or influx of the cation above control levels in PMA-activated neutrophils. These data demonstrate that FMLP, OZand A23187-mediated alterations in neutrophil cytosolic Ca²⁺ are due to mobilization of both intracellular and extracellular cation, while activation of neutrophils by PMA is independent of alterations in cytosolic Ca²⁺.     

High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus

Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Hillemanns P, Dörk T. High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital‐based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first‐degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first‐degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non‐carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.     

The clinical characteristics of Asian and Caucasian patients on Bradford's Low Vision Register

AIM: To analyse the clinical characteristics of patients on the Bradford Low Vision Register with regards to the type (partially sighted or blind), sex, race, causes and age at registration. METHODS: All the data were obtained from the Morley Street Resource Centre, which keeps records of all registrations in the Bradford Metropolitan District. Information including postcode, date of birth, age, gender, ethnic group, degree, date of registration, cause of registration and age at registration were entered into a database. RESULTS: Of all registrations, 64% were blind and 36% were partially sighted. Asians were younger at registration and there were a significantly lower number of females compared to Caucasians. When data were analysed for the different age groups, in the older group of over 65 years, Asians showed significantly more diabetic retinopathy (26.1%) compared to Asians (7.8%), while Caucasians demonstrated significantly more glaucoma (C: 29.3%; A: 17.4%). In the younger age group (<30 years), the leading causes for Asians were retinitis pigmentosa and nystagmus while for Caucasians it was congenital cataracts and optic atrophy. The proportion of Asians registered was significantly lower than expected from the projected population estimates in Bradford. CONCLUSIONS: The study indicates significant differences in the clinical profiles of the two racial groups. The data do not follow the predictions from published population estimates, with Asians, especially females, being under-represented in the register.