PubMed Health⌕ Search

Biomedical subjects

Alain Tremblay

Publications and source records attributed to Alain Tremblay.

10 recordsLinked to original sources
PubMed2006

Nucleotide-resolution mapping of topoisomerase-mediated and apoptotic DNA strand scissions at or near an MLL translocation hotspot.

The emergence of therapy-related acute myeloid leukemia (t-AML) has been associated with DNA topoisomerase II (TOP2)-targeted drug treatments and chromosomal translocations frequently involving the MLL, or ALL-1, gene. Two distinct mechanisms have been implicated as potential triggers of t-AML translocations: TOP2-mediated DNA cleavage and apoptotic higher-order chromatin fragmentation. Assessment of the role of TOP2 in this process has been hampered by a lack of techniques allowing in vivo mapping of TOP2-mediated DNA cleavage at nucleotide resolution in single-copy genes. A novel method, extension ligation-mediated polymerase chain reaction (ELMPCR), was used here for mapping topoisomerase-mediated DNA strand breaks and apoptotic DNA cleavage across a translocation-prone region of MLL in human cells. We report the first genomic map integrating translocation breakpoints and topoisomerase I, TOP2, and apoptotic DNA cleavage sites at nucleotide resolution across an MLL region harboring a t-AML translocation hotspot. This hotspot is flanked by a TOP2 cleavage site and is localized at one extremity of a minor apoptotic cleavage region, where multiple single- and double-strand breaks were induced by caspase-activated apoptotic nucleases. This cleavage pattern was in sharp contrast to that observed approximately 200 bp downstream in the exon 12 region, which displayed much stronger apoptotic cleavage but where no double-strand breaks were detected and no t-AML-associated breakpoints were reported. The localization and remarkable clustering of the t-AML breakpoints cannot be explained simply by the DNA cleavage patterns but might result from potential interactions between TOP2 poisoning, apoptotic DNA cleavage, and DNA repair attempts at specific sites of higher-order chromatin structure in apoptosis-evading cells. ELMPCR provides a new tool for investigating the role of DNA topoisomerases in fundamental genetic processes and translocations associated with cancer treatments involving topoisomerase-targeted drugs.

Apoptosis↗
PubMed2006

Single-center experience with 250 tunnelled pleural catheter insertions for malignant pleural effusion.

INTRODUCTION: Malignant pleural effusions (MPEs) are a common cause of dyspnea in patients with advanced cancer. Tunnelled pleural catheters (TPCs) can be used in patients with this condition, but the published experience with them is limited. OBJECTIVE: To describe the use of TPCs in the management of MPE in a large group of patients in a clinical setting. METHODS: Retrospective analysis of 250 sequential TPC insertions in patients with MPEs in a single center. RESULTS: Two hundred fifty TPC procedures for MPE were performed in 223 patients (19 contralateral procedures and 8 repeat ipsilateral procedures) during a 3-year period. Symptom control was complete following 97 procedures (38.8%), was partial in 125 procedures (50%), and was absent in 9 procedures (3.6%); in addition, there were 10 failed TPC insertions (4.0%) and 9 TPC insertions (3.6%) without assessment of symptoms at the 2-week follow-up visit. Spontaneous pleurodesis occurred following 103 of the 240 successful TPC procedures (42.9%) and was more frequent when < or = 20% of the hemithorax contained fluid at the 2-week follow-up visit (57.2% vs 25.3%, respectively; p < 0.001). Catheters stayed in place for a median duration of 56 days. Following successful TPC placement, no further ipsilateral pleural procedures were required in 90.1% of cases. The overall median survival time following TPC insertion was 144 days. Complication rates were low and compared favorably with those seen with other treatment options. CONCLUSIONS: TPC placement is an effective method of palliation for MPE that allows outpatient management and low complication rates. The insertion of a TPC should be considered as a first-line treatment option in the management of patients with MPE.

Adult↗
PubMed2003

Effects of intensive fishing on the structure of zooplankton communities and mercury levels.

Following the impoundment of hydroelectric reservoirs, a small fraction of the mercury (Hg) in the flooded soils is transformed and released into the ecosystem. This causes an increase in the mercury level in the food chain, particularly in piscivorous fish, and represents a potential risk for human health. In 1998, Hydro-Québec carried out an intensive fishing campaign to examine the feasibility of using intensive fishing as a mitigation tool. The goal of this particular part of the project was to evaluate the impact of intensive fishing on the zooplanktonic communities' structure and mercury levels. Specifically, the effects of intensive fishing on: (1) total biomass and zooplankton size structure (>500, 200-500, 100-200 and 53-100 microm); (2) species composition; and (3) total mercury and methylmercury (MeHg) concentrations in zooplankton of different size fractions were studied. Although important decreases were observed in total zooplankton biomass or its size structure, it cannot be related to the intensive fishing. The results, however, show major changes in the dominance of macrozooplanktonic species in fished lakes as opposed to reference lakes. Similarly, in contrast to the reference lakes, mercury and MeHg concentrations in the four size fractions of the zooplanktonic communities changed from 1998 to 2000 in the fished lakes. The MeHg concentration increased from approximately 20 to 200 ng/gdw from the 53 to 500 microm mesh size fraction, showing a biomagnification in the food chain. The canonical correspondence analysis showed that lakes dominated by Holopedium gibberum presented higher concentrations of Hg and MeHg than lakes dominated by Daphnia spp.

Animals↗
PubMed2003

Impact of body mass index on outcomes following critical care.

STUDY OBJECTIVES: To determine the impact of body mass index (BMI) on outcomes in critically ill patients. DESIGN: Retrospective analysis of a large multi-institutional ICU database. MEASUREMENTS: The influence of BMI classification (underweight, < 20 kg/m(2); normal [control subjects], 20 to 25 kg/m(2); overweight, 25 to 30 kg/m(2); obese, 30 to 40 kg/m(2); severe obesity, > 40 kg/m(2)) on hospital survival, functional status at hospital discharge, and ICU/hospital length of stay (LOS) was analyzed via multivariate analysis, adjusting for age, gender, type of hospital admission, and severity score (ie, simplified acute physiologic score [SAPS] II and mortality prediction model [MPM] at time zero). Univariate analysis also was performed according to the quartile of the severity score. All comparisons were to the normal BMI group. RESULTS: Of 63,646 patient datasets, 41,011 were complete for height, weight, and at least one of the two severity scores. We found increased mortality in underweight patients (odds ratio [OR] of death: SAPS group, 1.19; MPM group, 1.26) but not in overweight, obese, or severely obese patients. ICU and hospital LOS were increased in both the severely obese (OR of discharge: ICU, 0.81 and 0.84, respectively; hospital, 0.83 and 0.87, respectively) and underweight groups (OR of discharge: ICU, 0.96 and 0.94, respectively; hospital, 0.91 and 0.90, respectively). Only in the SAPS group did the obese group have increased ICU LOS (OR, 0.96) and hospital LOS (OR, 0.96). Functional status at discharge was impaired in underweight patients (OR of disability: ICU, 1.11; hospital, 1.19). Overweight patients had decreased discharge disability (OR of disability: SAPS, 0.93; MPM, 0.94), while the results in the obese group were discordant between the two severity score groups (SAPS, not significant; MPM, 0.91; p < 0.05 for all ORs). CONCLUSIONS: Low BMI, but not high BMI, is associated with increased mortality and worsened hospital discharge functional status. LOS is increased in severely obese patients and, to a lesser extent, in underweight patients. Patients in the overweight and obese BMI groups may have improved mortality and discharge functional status.

Adult↗
PubMed2003

Endobronchial phototoxicity of WST 09 (Tookad), a new fast-acting photosensitizer for photodynamic therapy: preclinical study in the pig.

Photodynamic therapy (PDT) has been used for many years for both palliative and curative treatment of bronchial carcinomas. However, prolonged skin phototoxicity and reduced depth of penetration has limited the widespread use of PDT. We studied the endobronchial phototoxicity of a novel photosensitizer, WST 09 (Tookad). Fourteen pairs of Large White-Landrace male piglets were given intravenous WST 09 followed by laser light illumination of the left mainstem bronchus. Different settings for light dose (fluence), fluence rate (FR), drug dose (D) and drug-light interval (DLI) were applied to each pair. Bronchial toxicity was assessed with repeat bronchoscopic photographic evaluation as well as by pathologic examination following autopsy. Animals developed no toxicity, moderate toxicity or severe toxicity. Increased toxicity was seen with increasing D and fluence and decreasing DLI, whereas no increased toxicity was seen with higher FR. PDT-related histological changes in the normal bronchus confirm the vascular effect of WST 09. Depending on the parameter settings for fluence, D and DLI, the lesions ranged from focal intramucosal ischemia to transmural infarction with subsequent acute inflammation and fibrosis. Clinically feasible parameters for drug and light dosimetry were documented. These data will be important in determining safe starting doses for human phase I/II studies.

Animals↗
PubMedDate not supplied

Endobronchial electrocautery and argon plasma coagulation: a practical approach.

The present review covers the technical and practical aspects of endobronchial electrocautery, including argon plasma coagulation, which have great potential for widespread use by pulmonologists around the world. The various electrocautery modes, power settings and electrode probes are described in detail, and the authors' clinical and technical approach is demonstrated with a narrative description and brief case presentations. Malignant airway obstruction, hemoptysis, web-like stenosis, stent related granulation tissue and early lung carcinomas are the most common indications for treatment. Advantages of electrocautery, such as low cost, rapid effect, safety and ease of use, are contrasted to other endobronchial therapeutic modalities. Published experience with electrocautery is reviewed.

Bronchial Diseases↗