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Biomedical subjects

E Yu

Publications and source records attributed to E Yu.

At least 19 recordsLinked to original sources
PubMed2006

3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours.

The purpose of this study was to validate the accuracy and reliability of volume measurements obtained using three-dimensional (3D) thoracoscopic ultrasound (US) imaging. Artificial "tumours" were created by injecting a liquid agar mixture into spherical moulds of known volume. Once solidified, the "tumours" were implanted into the lung tissue in both a porcine lung sample ex vivo and a surgical porcine model in vivo. 3D US images were created by mechanically rotating the thoracoscopic ultrasound probe about its long axis while the transducer was maintained in close contact with the tissue. Volume measurements were made by one observer using the ultrasound images and a manual-radial segmentation technique and these were compared with the known volumes of the agar. In vitro measurements had average accuracy and precision of 4.76% and 1.77%, respectively; in vivo measurements had average accuracy and precision of 8.18% and 1.75%, respectively. The 3D thoracoscopic ultrasound can be used to accurately and reproducibly measure "tumour" volumes both in vivo and ex vivo.

Agar↗
PubMed2004

Evaluation of intra- and inter-fraction motion in breast radiotherapy using electronic portal cine imaging.

Breast irradiation is one of the most challenging problems in radiotherapy due to the complex shape of the target volume, proximity of radiation sensitive normal structures and breathing motion. It was the aim of the present study to use electronic portal imaging (EPI) during treatment to determine intra- and inter-fraction motion in patients undergoing radiotherapy and to correlate the magnitude of motion with patient specific parameters. EPI cine images were acquired from the medial tangential fields of twenty radiotherapy patients on a minimum of 5 days each over the course of their treatment. The treatments were administered using 10 MV X-rays and dynamic wedges on a Varian Clinac 2100CD linear accelerator. Depending on the incident dose and the angle of the wedge, between 4 and 16 images could be acquired in one session using an EPI device based on liquid ionization chambers (Varian). The border between lung and chest-wall could be easily detected in all images and quantitative measurements were taken for the amount of lung in the field and the distance of the breast tissue from the field edges. Inter-fraction variability was found to be about twice as large as intra-fraction variability. The largest variability was detected in cranio/caudal direction (intra-fraction: 1.3 +/- 0.4 mm; inter-fraction: 2.6 +/- 1.3 mm) while the lung involvement varied by 1.1 +/- 0.2 mm and 1.8 +/- 0.6 mm intra- and inter-fraction, respectively. This indicates that the effect of breathing motion on the amount of radiated lung was not of major concern in the patients studied. Of other patient specific parameters such as body weight, breast separation, field size and location of the target, only increasing age was significantly correlated with larger inter-fraction motion. Acquisition of EPI cine loops proved to be a quick and easy technique to establish the amount of patient movement during breast radiotherapy. The relatively small variability found in the present pilot study justifies considerations for more conformal dose delivery.

Aged↗
PubMed2002

Monte Carlo simulations of DNA damage from incorporated cold iodine following photoelectrically induced Auger electron cascades.

Radiation-induced damage in nucleosomal DNA from Auger electron cascades due to incorporated cold IUdR has been modelled through Monte Carlo simulations. Probabilities of DNA double strand break (DSB) production following a vacancy in the K, L, M and N shells of iodine are estimated. DSB complexity from the base damage accompanying a break was also estimated. Multiple DSB events were analysed for correlated breaks due to nucleosome periodicity. The probability of an Auger cascade causing at least one DSB strongly depended on the shell in which the initial vacancy was produced. This probability was approximately 0.35 for K and L shells and fell to 0.02 for the N shell. As expected, DSBs were predominantly induced in a nucleosome containing incorporated iodine and were accompanied with extensive base damage. Analysis of multiple DSB events showed that approximately 14% of the DSBs produced following a vacancy in the L1 orbital can be interpreted as correlated with base pair separation attributable to the nucleosome periodicity. The data generated in this work provide a basis for the development of photon-activation therapy using kilovoltage X rays incident upon IUdR sensitised tumours.

Computer Simulation↗
PubMed2001

Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis.

Studies have shown that rates of liver disease are higher in persons who are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) than they are in persons with HCV alone, but estimates of risk vary widely and are based on data for dissimilar patient populations. We performed a meta-analysis to quantify the effect of HIV coinfection on progressive liver disease in persons with HCV. Eight studies were identified that included outcomes of histological cirrhosis or decompensated liver disease. These studies yielded a combined adjusted relative risk (RR) of 2.92 (95% confidence interval [CI], 1.70-5.01). Of note, studies that examined decompensated liver disease had a combined RR of 6.14 (95% CI, 2.86-13.20), whereas studies that examined histological cirrhosis had a pooled RR of 2.07 (95% CI, 1.40-3.07). There is a significantly elevated RR of severe liver disease in persons who are coinfected with HIV and HCV. This has important implications for timely diagnosis and consideration of treatment in coinfected persons.

HIV Infections↗
PubMed2001

Practice guideline on prophylactic cranial irradiation in small-cell lung cancer.

PURPOSE: To develop an evidence-based clinical practice guideline that would address the following questions: (a) What is the role of prophylactic cranial irradiation (PCI) in patients with limited or extensive stage small-cell lung cancer (SCLC) who have achieved complete remission in response to induction therapy (chemotherapy or chemoradiotherapy)? (b) What dose and fractionation schedules of PCI are optimal? (c) Does the use of PCI in patients with SCLC in complete remission affect quality of life? Survival, disease-free survival, quality of life, and adverse effects were the outcomes of interest. METHODS AND MATERIALS: A systematic review of the published literature was undertaken to provide the data for an evidence-based practice guideline. RESULTS: Six randomized controlled trials and one fully published individual patient data meta-analysis were included in the systematic review of the evidence. For patients who have achieved complete response after induction therapy, there is evidence of a disease-free survival benefit (4 of 6 trials) and an overall survival benefit (meta-analysis). There is insufficient evidence to make a definitive recommendation with respect to dose. There is some indication that 30-36 Gy in 2-3 Gy per fraction, or a biologically equivalent dose, may produce a better outcome than a lower dose or less aggressive fractionation regimen. The schedule commonly used in Canada is 25 Gy in 10 fractions over 2 weeks. Data from further research, including a trial currently ongoing that compares 25 Gy in 10 fractions with 36 Gy in 18 fractions, will be required to determine optimal dose of PCI. There is insufficient evidence to make recommendations concerning the optimal timing of PCI in relation to the administration of chemotherapy. Lung DSG members generally felt that it should be given as soon as possible after completion of chemotherapy. There is evidence from trials with data for up to 2 years of follow-up that prophylactic cranial irradiation does not produce significant late neurotoxicity. There is evidence from one trial that prophylactic cranial irradiation does not have a detrimental effect on quality of life in the first 12 months following the completion of therapy. There is insufficient evidence to comment on the long-term effects of prophylactic cranial irradiation on quality of life. CONCLUSION: For adult patients with limited or extensive SCLC who achieve a complete remission with induction therapy, PCI is recommended.

Carcinoma, Small Cell↗
PubMed2001

Monte Carlo simulations and measurement of DNA damage from x-ray-triggered auger cascades in iododeoxyuridine (IUdR).

We investigated the DNA damage from Auger electrons emitted from incorporated stable iodine (127I), following photoelectric absorption of external x-rays. The effectiveness of the Auger electrons in producing DNA double-strand breaks (DSB) was determined theoretically, using Monte Carlo simulations of the radiation physics and chemistry, and was shown to be in reasonable agreement with DNA damage measured using the comet assay. The DSB yields were measured in CHO cells for 60Co (as a non-Auger-promoting radiation) and for tungsten-filtered 100 kVp x-rays capable of producing Auger electron emission. The theoretical study showed that on average, 2.5 Auger electrons were emitted for N-shell orbital vacancies and up to 10 Auger electrons were emitted from L1-shell vacancies. These Auger bursts produced approximately 0.03 DSB per N-shell vacancy and 0.3 DSB per K-shell or L-shell vacancy. The calculated yield of DSB from Auger cascades per unit dose (1 Gy) in water was approximately 1.7 for tungsten-filtered 100 kVp x-rays, assuming 20% IUdR substitution of thymidine. The comet assay yielded an experimental value of 3.6+/-1.6 per 1 Gy for the same conditions. The Monte Carlo simulations also demonstrated a high complexity of DSB produced by Auger cascades with virtually all DSB from inner shell orbitals (i.e. K, L shells) accompanied by compounded strand breakage and base damage, indicating a difficult lesion to repair. This finding agrees well with comet assay results of DNA repair, where an increase in the DSB yield in IUdR-sensitized cells was shown to persist after a time of 24 h. We conclude that Auger cascades in iodine produce a modest increase in the number of initial strand breaks of the order of 10% but the complex nature of these DSB makes them very difficult to repair or potentially prone to misrepair. The accentuated DNA damage may have major consequences for cell survival and may be exploitable in kilovoltage photon activation therapy (PAT) of tumors sensitized with iodine.

Animals↗
PubMed2001

The closeout process for a clinical trial terminated early for lagging enrollment and inadequate follow-up.

Closeout of a clinical trial, whether carried out to its original completion of full accrual and attendant follow-up or stopped prematurely because of early indications of efficacy or adverse toxicity, presents challenges in many areas. Closing a clinical trial that fails to adequately accrue and/or successfully follow up patients may exacerbate these problems. The issues involved in the early termination of the Low-Dose Oral Alpha Interferon Trial are described. Control Clin Trials 2001;22:49-55

Administration, Oral↗
PubMed2001

Isocitrate dehydrogenase as a marker of centrilobular hepatic necrosis in the experimental model of rats.

BACKGROUND AND AIMS: Serum alanine aminotransferase (ALT) and aspartate aminotransferase may not detect centrilobular hepatic necrosis (CLN) of a mild degree because these enzymes are known to be located predominantly in the periportal area. The aim of this study was to evaluate the usefulness of plasma isocitrate dehydrogenase (ICDH), which is located predominantly in the centrilobular zone, as a marker of CLN. METHODS: In 56 adult male rats, centrilobular (n = 21) and periportal hepatic necrosis (PPN; n = 21) were induced experimentally by the intraperitoneal injection of bromobenzene and allylalcohol, respectively. Seven rats were used as solvent controls in both groups. Isocitrate dehydrogenase and ALT activities were measured in the plasma of rats with mild to moderate hepatic necrosis (17 CLN and 19 PPN). Isocitrate dehydrogenase and ALT were compared according to the sampling time (12, 24 and 48 h) and the location of hepatic necrosis. Ratios of ICDH/ALT were also calculated and compared between CLN and PPN groups at any time points. RESULTS: Plasma ICDH activities were higher in rats with CLN than in those with PPN. In contrast, plasma ALT levels were higher in rats with PPN than in those with CLN at 12 h and were similar in both groups after 12 h. The ICDH/ALT ratios were much higher in rats with CLN compared to those with PPN (P< 0.001). The ratios were above 1.0 in 13 of 17 rats (77%) with CLN in contrast to none of the 19 rats with PPN. CONCLUSIONS: Our data suggested that the plasma ICDH/ALT ratio might be useful to differentiate between mild to moderate degrees of CLN from PPN, at least in the experimental model of rats.

Alanine Transaminase↗
PubMed2001

Operational characteristics of a prototype x-ray needle device.

A prototype x-ray needle, which emits 62.5 kVp x-rays at the tip of a 20 cm long, 4 mm diameter steel needle, has been developed by Titan Pulse Sciences Incorporated (PSI) (Albuquerque, NM) and was tested for its suitability in brachytherapy applications in comparison with a similar device by the Photoelectron Corporation. The depth dose profiles were also compared with those of two common brachytherapy sources (125I and 192Ir). The depth dose characteristics of the radiation were comparable with the two brachytherapy sources with a slightly reduced attenuation gradient. The dose rate from the x-ray needle tip was relatively isotropic at the needle tip and was continuously adjustable over the range of 0 cGy min(-1) to upwards of 62 cGy min(-1) at a reference distance of 1 cm in air. We detected a significant proportion of x-rays generated along the needle shaft, and not at the needle tip, as intended. The energy spectrum emitted from this device had a peak intensity at 21 keV and an average energy of 28 keV. The beam was attenuated in both aluminium (the first half-value layer being less than 0.1 mm) and in water (50% dose at approximately 2 mm). These studies confirm that although there is potential for a system similar to this one for clinical applications, the simplistic electron guidance used in this particular prototype device limits it to research applications. Further optimization is required in focusing and steering the electron beam to the target, improving x-ray production efficiency and using x-ray target cooling to achieve higher dose rates.

Aluminum↗
PubMed2001

Overexpression of promyelocytic leukemia protein and alteration of PML nuclear bodies in early stage of hepatocarcinogenesis.

Promyelocytic leukemia protein (PML) is a major component of PML nuclear bodies (PML NBs). Fusion of promyelocytic leukemia alpha gene (PML) with retinoic acid receptor gene with the t (15;17) translocation causes disassembly of PML NBs, leading to development of acute promyelocytic leukemia. In contrast, PML overexpression as well as different morphological changes of PML NBs were described in a few solid tumors. In this study, the expression of PML through the multistep hepatocarcinogenesis was analyzed in 95 cases of human hepatocellular carcinomas (HCCs) for comparison along with dysplastic nodules (DNs) and background liver cirrhosis (LC) or chronic hepatitis by immunohistochemistry and immunoblot. In addition, cases of HCCs were further evaluated according to their histologic grade and etiology. The amount of PML as well as the number and size of PML NBs increased gradually through the progression from LC, DNs to HCCs. The overexpression of PML in HCCs was much more closely associated with HBV infection than HCV infection or alcoholic liver disease. The PML expression, however, was not correlated with histologic grade of HCCs. These results suggest that PML is involved in the early stage of multistep hepatocarcinogenesis, and HBV infection may be associated with the overexpression of PML and the morphological alteration of PML NBs.

Carcinoma, Hepatocellular↗
PubMed2001

Parenchymal and nonparenchymal cellular responses in human hepatic regeneration.

To characterize cellular responses during hepatic regeneration, we examined 13 explant livers and 5 liver allografts by immunohistochemistry for cytokeratin 7, HepPar1, CD68, alpha-smooth muscle actin (alpha-SMA) and proliferating cell nuclear antigen as well as reticulin and Masson-trichrome staining. Within a week after liver damage, elongated CD68-positive cells were detected along the border of necrotic area. The number of alpha-SMA-positive cells was slightly increased along the sinusoids. Ductular proliferation or fibrosis was negligible. After one or two weeks, the size and number of CD68-positive cells were markedly increased. alpha-SMA-positive cells increased in number within lobules and portal tracts. Ductular proliferation occurred predominantly at the limiting plate or along the border of necrotic areas. After one month, necrotic parenchyma was replaced by many ductules, CD68-positive cells, alpha-SMA-positive cells. Nodules of regenerating hepatocytes and irregular fibrosis were diffusely present. Other nonparenchymal cells were not significantly changed. These observations indicate that chronological interaction between nonparenchymal and parenchymal cells occur during the course of human hepatic regeneration and suggest extensive porto-periportal fibrosis more than a few months after the onset of fulminant hepatitis is a major indicator of chronic functional impairment necessitating liver transplantation.

Actins↗
PubMed2001

Computed tomography to assess pulmonary injury associated with concurrent chemo-radiotherapy for inoperable non-small cell lung cancer.

OBJECTIVE: To characterize serial computed tomography (CT) findings of pulmonary injury after a uniform regimen of concurrent chemo-radiotherapy in inoperable non-small cell lung cancer, and to compare the radiation-induced lung toxicity with other concurrent chemo-radiation regimens. METHODS: Twenty-four patients with advanced non-small cell lung cancer received 2 induction cycles of cisplatin and vinblastine, followed by 2 further cycles of cisplatin and vinblastine, concurrent with 60 Gy radiation at 2 Gy per fraction. Radiation-induced lung injury in the acute and chronic phases was assessed by serial CT scans and compared with preradiation baseline scans. Acute radiation pneumonitis was evaluated using the Common Toxicity Criteria, and chronic radiation fibrosis was graded according to the European Organisation for Research and Treatment of Cancer--Radiation Therapy Oncology Group Scale. RESULTS: Seventeen (81%) patients had characteristic CT findings of radiation-induced pulmonary damage, which were confined to the radiation ports. Although patchy nonhomogeneous and air-space opacities characterized acute radiation pneumonitis, and homogeneous opacities with loss of volume were typical for chronic fibrosis, ground-glass opacities were found frequently in both phases. Acute radiation pneumonitis grade 1 was seen in 29% and grade 2 in 9.5%. Chronic radiation fibrosis grades 1, 2 and 3 were found in 14%, 33% and 19% of the patients respectively. Median survival time was 13 months. CONCLUSION: CT enables detailed evaluation of radiation-induced pulmonary injury after concurrent chemo-radiation for inoperable non-small cell lung cancer. Although survival time with the present regimen is comparable to other concurrent chemo-radiation regimens, a high incidence of radiation injury was found, though the severity was not life threatening.

Adult↗
PubMed2000

Characterization of the cold stress-induced cyanobacterial DEAD-box protein CrhC as an RNA helicase.

We have shown previously that CrhC is a unique member of the DEAD-box family of RNA helicases whose expression occurs specifically under conditions of cold stress. Here we show that recombinant His-tagged CrhC, purified from Escherichia coli, is an ATP-independent RNA binding protein possessing RNA-dependent ATPase activity which is stimulated most efficiently by rRNA and polysome preparations. RNA strand displacement assays indicate that CrhC possesses RNA unwinding activity that is adenosine nucleotide specific. Unwinding of partially duplexed RNA proceeds in the 5'-->3' but not the 3'-->5' direction using standard assay conditions. Immunoprecipitation and far-western analysis indicate that CrhC is a component of a multisubunit complex, interacting specifically with a 37 kDa polypeptide. We propose that CrhC unwinds cold-stabilized secondary structure in the 5'-UTR of RNA during cold stress.

Adenosine Triphosphatases↗
PubMed2000

Radiation treatment for cervical esophagus: patterns of practice study in Canada, 1996.

PURPOSE: To assess the patterns of practice among Canadian radiation oncologists who treat esophageal cancers, using a trans-Canada survey, completed at the end of 1996. METHODS AND MATERIALS: One of 3 case presentations of different stages of cervical esophageal cancer was randomly assigned and sent to participating radiation oncologists by mail. Respondents were asked to fill in questionnaires regarding treatment techniques and to outline target volumes for the boost phase of radiotherapy. Radiation oncologists from 26 of 27 (96%) of all Canadian centers participated. RESULTS: High-energy X-rays (>/= 10 MV) were employed by 68% of the respondents in part of the treatment course. The majority (83%) of the radiation oncologists used at least two phases of treatment. Very few, 10 of 59 (17%), responses started with multifield treatment. The most frequently used prescription dose was 60 Gy/30 fractions/6 weeks, given with concurrent chemotherapy. Dose prescriptions were to the isocenter in 39 of 48 (81%) or to a particular isodose line in 9 of 48 (19%) of respondents. CONCLUSION: There was a variety of radiation treatment techniques in this trans-Canada survey. The majority of the patients had combined cisplatin-based chemoradiation. The isocenter was not used consistently as a dose prescription point.

Aged↗
PubMed2000

Nuclear matrix of calreticulin in hepatocellular carcinoma.

Nuclear matrix protein profiles of malignant cells vary from their normal counterparts. By two-dimensional gel electrophoresis, we analyzed nuclear matrix proteins in 11 hepatocellular carcinomas and compared them with corresponding non-neoplastic liver tissue. Although the compositions were mostly similar, several peptides were noted predominantly in the former. The most prominent one was an acidic protein of apparent Mr 62,000, which was identified to be calreticulin upon NH2-terminal amino acid sequencing. By immunoblotting, calreticulin was confirmed to be present abundantly in the nuclear matrix fraction of carcinomas but not in that of the nonmalignant liver tissue. Interestingly, the total content of calreticulin was similar between them. By immunofluorescence microscopy, evident nuclear immunostaining was detected in carcinomas. Calreticulin was also found to be in the nuclear matrices of various carcinoma cell lines. We conclude that calreticulin is a component of the nuclear matrix. The formation and/or expansion of the calreticulin-nuclear matrix may be related to the activated cell growth.

Adult↗