Serial Measurement of Sister Chromatid Exchanges in the Peripheral Lymphocytes of Patients with Lung Cancer Receiving Chemotherapy in Relation to Bone Marrow Toxicity

The frequencies of sister chromatid exchanges (SCE) in the peripheral lymphocytes of patients with lung cancer before and after initial chemotherapy were serially measured and the correlation between SCE frequencies and bone marrow toxicity was evaluated. The addition of mitomycin C to vindesine plus cisplatin increased SCE frequencies significantly in patients with non-small cell lung cancer. A significant increase in frequencies of SCE was observed in patients treated with cyclophosphamide plus adriamycin plus vincristine as compared with those treated with cisplatin plus etoposide in small cell lung cancer. A significant inverse correlation was observed between SCE frequencies in the peripheral lymphocytes 7 days after treatment ( x ) and the nadir value/pretreatment value of platelets ( y )( r = -0.685, P = 0.0007, y = 0.842–0.022 x ). The relation between SCE frequency and leukopenia showed the same trend as thrombocytopenia, but the correlation was not statistically significant ( r = - 0.444, P = 0.057). SCE assay may have potential clinical use for the prediction of chemotherapyinduced thrombocytopenia.     

中期妊娠应用甘遂引产妇女的姊妹染色单体交换

本文研究中期妊娠应用甘遂引产妇女,注药后对外周血淋巴细胞姊妹染色单体交换(SCE)率的影响。结果表明,用药后24小时每个细胞SCE率为7.82±0.13(S. E),注药后48小时SCE率为7.05±0.21(S. E)。用药前每个细胞SCE率分别为7.27±0.24(S. E)与7.08±0.23(S. E)。注药后与引产前相比较均无显著差异(P>0.05)。表明甘遂并非是致突变剂。     

Genotoxic and aneugenic properties of an imidazole derivative

To contribute to a more accurate characterization of the mutagenic and aneugenic effects of thiabendazole (TBZ), a widely used antiparasitic and food preservative drug, the induction of sister chromatid exchanges (SCEs) and mitotic spindle anomalies as cytogenetic end-points were investigated. Studies were carried out in Chinese hamster ovary (CHO) cells and human peripheral blood lymphocytes. A significant dose-dependent increase in SCE frequency was observed in CHO cells with S9-Mix (P < 0.01) in the 50-100 microg ml(-1) dose-range, while in the absence of S9-Mix, an enhancement of the SCE frequency was exhibited at the highest dose (P < 0.01). In CHO-K1 cells a significant increase in mitotic spindle anomalies (P < 0.01) was observed with the highest concentration assayed reflecting the specific effect of TBZ formulation at the microtubule level. Cell proliferation kinetics (CPK) were not modified by the addition of this pharmaceutical product. In human lymphocyte cultures, exposure to 100 microg ml(-1) TBZ formulation resulted in a significant decrease of the mitotic index (MI) (P < 0.003) and changes in the replication index (RI) (P < 0.05).     

Sister chromatid exchange in vivo in mice: I. The influence of increasing doses of bromodeoxyuridine

Bromodeoxyuridine (BrdUrd) pellets weighing either 20, 25, 30, 35, 40, 45, or 53 mg were implanted subcutaneously in strain DBA/2J male mice. Femoral bone marrow cells were analyzed for sister chromatid exchange (SCE) and chromosome aberration frequencies, mitotic indices, and cellular replication kinetics. Small but statistically significant BrdUrd dose-dependent increases of SCEs were observed, whereas chromosome aberrations were induced at low frequencies and occurred independently of BrdUrd dose. The mitotic index remained relatively constant for all doses. A slight inhibition of cellular replication, as manifested by a reduction in third division cells at the 40- and 45-mg doses, was observed. The use of an intense fluorescent light source in the fluorescence-plus-Giemsa technique provided consistently good sister chromatid differentiation at pellet doses substantially lower than those previously used by other investigators.     

Determination of apoptosis, uracil incorporation, DNA strand breaks, and sister chromatid exchanges under conditions of thymidylate deprivation in a model of BER deficiency

Thymidylate synthase (TS) is an important target of several chemotherapeutic agents. During TS inhibition, dTTP levels decrease with a subsequent increase in dUTP. Uracil incorporated into the genome is removed by base excision repair (BER). BER has been hypothesized to play a role in the response to thymidylate deprivation, despite a lack of direct evidence. We previously found that beta-pol null murine fibroblasts were approximately six-fold more resistant than wild-type cells to raltitrexed, a folate-based inhibitor specific for TS. In this study, a number of endpoints were determined to understand the influence of BER and beta-pol during raltitrexed treatment. Raltitrexed induced apoptosis in wild-type cells to a greater extent than in beta-pol null cells. A PARP inhibitor decreased the sensitivity to raltitrexed, although the extent was not different between wild-type and beta-pol null cells. No evidence was seen for extensive strand break formation that preceded apoptosis, although raltitrexed induced more sister chromatid exchanges in wild-type cells. Increased levels of uracil in DNA were detected following treatment in wild-type and beta-pol null cells. However, uracil levels were only approximately two-fold higher in DNA from treated cells compared to untreated. Uracil DNA glycosylase activity was slightly higher in beta-pol null cells, although not sufficiently different to explain the difference in sensitivity to raltitrexed. Taken together, the data suggest that the sensitivity of the wild-type cells to raltitrexed is not associated with activation of PARP-1 dependent BER, extensive uracil incorporation into DNA and persistent strand breaks, but rather with changes suggestive of DNA recombination.     

The Impact of Health Information Exchange on Health Outcomes

Background and Objective

Healthcare professionals, industry and policy makers have identified Health Information Exchange (HIE) as a solution to improve patient safety and overall quality of care. The potential benefits of HIE on healthcare have fostered its implementation and adoption in the United States. However,there is a dearth of publications that demonstrate HIE effectiveness. The purpose of this review was to identify and describe evidence of HIE impact on healthcare outcomes.

Methods

A database search was conducted. The inclusion criteria included original investigations in English that focused on a HIE outcome evaluation. Two independent investigators reviewed the articles. A qualitative coding approach was used to analyze the data.

Results

Out of 207 abstracts retrieved, five articles met the inclusion criteria. Of these, 3 were randomized controlled trials, 1 involved retrospective review of data, and 1 was a prospective study. We found that HIE benefits on healthcare outcomes are still sparsely evaluated, and that among the measurements used to evaluate HIE healthcare utilization is the most widely used.

Conclusions

Outcomes evaluation is required to give healthcare providers and policy-makers evidence to incorporate in decision-making processes. This review showed a dearth of HIE outcomes data in the published peer reviewed literature so more research in this area is needed. Future HIE evaluations with different levels of interoperability should incorporate a framework that allows a detailed examination of HIE outcomes that are likely to positively affect care.     

Cutaneous metastases from internal malignancies

Cutaneous metastases of internal malignancies still seem to occur infrequently, although medical publications report an incidence rate of up to 10.4%. Common sense, however, fosters suspicion that we might underdiagnose the problem distracted by harder striking facets of an advanced disease. With contemporary knowledge, morphology and behavior of cutaneous metastases resemble each other regardless of the site of origin. This article itemizes clinical presentations according to organ systems, specific features, and differential diagnoses. In general, the survival turned out to be less than 12 months. But incremental awareness of cutaneous metastases proclaims this paradigm insufficient. Although excision is the local treatment of choice, investigations attempt to propose tumor-specific chemotherapeutic/immunological approaches. This paper endeavors to critically review the state of the art concerning the clinic, prognosis, and therapeutic concepts.     

Acute Wood or Coal Exposure with Carbon Monoxide Intoxication Induces Sister Chromatid Exchange

Objective: The object of this study was to investigate the genotoxic effect of acute overexposure to combustion products originating from coal or wood stoves in patients presenting with acute carbon monoxide intoxication. Study Design: In a prospective study, we analyzed the frequency of sister chromatid exchange and the carboxyhemoglobin concentration in 20 consecutive patients without a history of smoking or drug use who had been treated in the Emergency Care Unit of Istanbul Medical Faculty due to acute carbon monoxide intoxication. All of these cases were domestic accidents due to dysfunctioning coal or wood stoves. The results were compared with a control group of 20 nonsmoking, nondrug-using healthy individuals matched for age, sex, and absence of other chemical exposure. Results: The mean sister chromatid exchange frequency per metaphase was significantly higher in the study group compared to the control group: 8.11±2.39 vs. 6.33±1.60 (p=0.008). We found that there was no positive correlation between the blood carboxyhemoglobin concentration and sister chromatid exchange frequency. Conclusions: These results suggest that acute exposure to combustion products of wood or coal is genotoxic to DNA. Potential causes of genotoxicity include known mutagenic compounds present in coal or wood smoke and ash, oxygen radicals formed during combustion, as well as hypoxic and reperfusion injury mechanisms initiated by carbon monoxide intoxication. Additional studies on separate carbon monoxide exposure from smoke and ash are needed to understand individual genotoxic contributions and mechanisms.     

Condensins: universal organizers of chromosomes with diverse functions

Condensins are multisubunit protein complexes that play a fundamental role in the structural and functional organization of chromosomes in the three domains of life. Most eukaryotic species have two different types of condensin complexes, known as condensins I and II, that fulfill nonoverlapping functions and are subjected to differential regulation during mitosis and meiosis. Recent studies revealed that the two complexes contribute to a wide variety of interphase chromosome functions, such as gene regulation, recombination, and repair. Also emerging are their cell type- and tissue-specific functions and relevance to human disease. Biochemical and structural analyses of eukaryotic and bacterial condensins steadily uncover the mechanisms of action of this class of highly sophisticated molecular machines. Future studies on condensins will not only enhance our understanding of chromosome architecture and dynamics, but also help address a previously underappreciated yet profound set of questions in chromosome biology.     

纳米载银室温固化PMMA材料对雄性小鼠生殖系统的影响

目的:研究添加2%浓度纳米载银无机抗菌剂的室温固化型聚甲基丙烯酸甲酯(PMMA)材料对雄性小鼠生殖系统的影响。方法:将雄性昆明小鼠随机分组,动物实验模型建立完成后,处死。计算小鼠体重增长率、睾丸脏器系数,观察睾丸组织的病理学改变,进行精子活动率检测、计数和畸形率计算。采用初级精母细胞染色体畸变实验和精原细胞姊妹染色单体互换(SCE)实验检测实验材料对小鼠初级精母细胞及精原细胞染色体的影响。结果:添加2%浓度纳米载银室温固化PMMA材料对小鼠体重增长率、睾丸脏器系数以及精子计数、活动率和畸形率均无显著性影响,各实验组睾丸组织病理切片与阴性对照组无明显差异。添加2%浓度纳米载银室温固化PMMA材料对小鼠的初级精母细胞染色体无致畸变作用;各实验组精原细胞SCE率与阴性组无显著性差异。结论:添加2%浓度纳米载银室温固化PMMA材料对雄性小鼠生殖系统无显著影响。