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Biomedical subjects

M Desrosiers

Publications and source records attributed to M Desrosiers.

At least 19 recordsLinked to original sources

A transferability study of the EPR-tooth-dosimetry technique.

The transferability of a measurement protocol from one laboratory to another is an important feature of any mature, standardised protocol. The electron paramagnetic resonance (EPR)-tooth dosimetry technique that was developed in Scientific Center for Radiation Medicine, AMS, Ukraine (SCRM) for routine dosimetry of Chernobyl liquidators has demonstrated consistent results in several inter-laboratory measurement comparisons. Transferability to the EPR dosimetry laboratory at the National Institute of Standards and Technology (NIST) was examined. Several approaches were used to test the technique, including dose reconstruction of SCRM-NIST inter-comparison samples. The study has demonstrated full transferability of the technique and the possibility to reproduce results in a different laboratory environment.

Electron Spin Resonance Spectroscopy↗

Management of acute bacterial rhinosinusitis: current issues and future perspectives.

Acute bacterial rhinosinusitis (ABRS), which manifests as an inflammation of at least one of the paranasal sinuses, is a major public health issue in developed countries. Diagnosis and treatment of ABRS can pose significant challenges in clinical practice, including difficulty in differentiation between viral and bacterial infection and a lack of simple, reliable and convenient methods for definitive diagnosis. Treatment choice is also a challenge because a decision is typically made empirically; therefore, the selection of therapy should be based on knowledge of local patterns of antimicrobial resistance, spectrum of activity against the most common ABRS pathogens (including those that are resistant to penicillins and macrolides) and pharmacodynamic potency. Current guidelines for diagnosis and treatment of ABRS in various countries share some similarities but also have important differences. Criteria for making the clinical diagnosis of sinusitis vary only slightly from country to country, while recommendations of therapy reflect the local impact of bacterial resistance.

Acute Disease↗

Correction factors in the EPR dose reconstruction for residents of the Middle and Lower Techa riverside.

During 1949-1956, the first Soviet nuclear weapons plant, Mayak, released about 7.6 x 10(7) m(-3) of liquid radioactive waste with a total activity of 10(17) Bq into the Techa River (Southern Urals, Russia). 90Sr contributed 11.6% to the total waste radioactivity. As a result of these radioactive discharges, about 28,000 local residents were exposed to ionizing radiation, and some of them received relatively high doses. Internal exposure of the population residing at the Middle and Lower Techa riverside was mostly from 90Sr deposited in bone and tooth tissues. In order to reconstruct radiation doses to this population group, a study of 35 teeth extracted from local residents was carried out using electron paramagnetic resonance measurements. A total of 73 samples from these 35 teeth (tooth enamel, 33; crown dentin, 20; and root dentin, 20) were prepared and measured with electron paramagnetic resonance. The study revealed high doses (up to 15 Gy) absorbed in tooth enamel of the individuals born during 1945-1949, which was attributed to very high local 90Sr concentration in tooth enamel of this particular age group in the population. The analysis presented here takes into account (a) the time courses both of the release/intake of 90Sr and of the tooth formation, and (b) expected variations in measured absorbed doses due to differing geometric sizes of tooth structures. This methodology enables a more consistent picture to be developed of the 90Sr intake by the Middle and Lower Techa riverside population, based on electron paramagnetic resonance tooth dosimetry.

Age Factors↗

Evaluation of the nasal response to histamine provocation with acoustic rhinometry.

The objectives of this study were to evaluate the reproducibility of the nasal response to histamine with the acoustic rhinometer and to compare the responses in normal and rhinitic subjects. Our study comprised 10 normal and 10 rhinitic subjects. Each subject had six sessions of provocation: three with histamine phosphate at a concentration of 4 mg/mL and three with saline phosphate provocation. Basal measurements of the nasal volumes were taken initially and then at 5-minute intervals for 90 minutes. All rhinometric measurements were made bilaterally and in triplicate. The variation between the triplicate measurements (2% +/- 0.1% [95% CI]) and the variation between the basal measurements (7.3% +/- 3.1% [95% CI]) were very low in both normal and rhinitic subjects. The comparison of the average congestive response of the normal subjects revealed that they responded steadily for at least 90 minutes to histamine and saline but that the response to histamine was significantly more important. There was also a low variability in the congestive response between the subjects. The comparison of the average congestive response of the rhinitic subjects revealed that their responses were more dynamic, not steady, compared with those of the normal subjects. The response was statistically significant only in the first few intervals. The comparison of the average congestive response to saline suggests that rhinitic subjects present a more important response than normal subjects. The comparison of the average congestive response to histamine between rhinitic and normal subjects was not statistically different but was different in the shape of the response pattern. Acoustic rhinometry is a highly reproducible method for measuring nasal volume in our provocation protocol. Histamine nasal provocation leads to a pattern of congestive response that is different in normal and rhinitic subjects. Histamine nasal provocation seems to be useful in addition to the study of nasal hyperreactivity and, as such, could permit differentiation between rhinitic and nonrhinitic subjects.

Adult↗

Temperature stabilization of alanine dosimeters used for food processing and sterilization

The International Atomic Energy Agency has established a dose quality audit service for radiation processing facilities. The objective of the service is to provide an independent check on the routine dosimetry system in use at the facility. The audit service is based on the use of alanine EPR dosimetry. Generally, alanine dosimeters are irradiated at the facility together with a product, and the response is then analyzed at the IAEA laboratory. Practice of the audit service has shown that the main uncertainty in alanine dosimetry is due to absence of temperature control at the irradiation facilities. Here, a method for stabilizing the temperature of the dosimeter during irradiation is proposed.

Journal Article↗

Impaired recruitment of the small GTPase rab7 correlates with the inhibition of phagosome maturation by Leishmania donovani promastigotes.

We have shown recently that one of the survival strategies used by Leishmania donovani promastigotes during the establishment of infection in macrophages consists in inhibiting phagosome-endosome fusion. This inhibition requires the expression of lipophosphoglycan (LPG), the predominant surface glycoconjugate of promastigotes, as parasites expressing truncated forms of LPG reside in phagosomes that fuse extensively with endocytic organelles. In the present study, we developed a single-organelle fluorescence analysis approach to study and analyse the intracellular trafficking of 'fusogenic' and 'low-fusogenic' phagosomes induced by an LPG repeating unit-defective mutant (Ipg2 KO) or by wild-type L. donovani promastigotes respectively. The results obtained indicate that phagosomes containing mutant parasites fuse extensively with endocytic organelles and transform into phagolysosomes by losing the early endosome markers EEA1 and transferrin receptor, and acquiring the late endocytic and lysosomal markers rab7 and LAMP1. In contrast, a majority of 'low-fusogenic' phagosomes containing wild-type L. donovani promastigotes do not acquire rab7, wheres they acquire LAMP1 with slower kinetics. These results suggest that L. donovani parasites use LPG to restrict phagosome-endosome fusion at the onset of infection in order to prevent phagosome maturation. This is likely to permit the transformation of hydrolase-sensitive promastigotes into hydrolase-resistant amastigotes within a hospitable vacuole not displaying the harsh environment of phagolysosomes.

Animals↗

Endoscopic orbital decompression with preservation of an inferomedial bony strut: minimization of postoperative diplopia.

With the increasing sophistication and safety of endoscopic orbital decompression, the technique is seen by many as an attractive and less morbid alternative to traditional open techniques. This rationale also makes the procedure more acceptable for individuals considering decompression for cosmetic reasons. As a result, complications such as postoperative diplopia assume greater significance. Preservation of an inferomedial bony strut has been postulated to reduce the incidence of postoperative diplopia in transconjunctival, but not endoscopic, orbital decompression for dysthyroid ophthalmopathy. We present a consecutive series of 11 subjects (21 eyes) who underwent transnasal endoscopic medial and inferior decompression of the orbits bilaterally. All patient charts were reviewed in a retrospective fashion and ophthalmologic, surgical, and cosmetic data were recorded, with callback of patients with incomplete data sets. All cases were performed under general anaesthesia. Preservation of the strut was possible in 15 of 21 eyes. Visual acuity was preserved or improved in all 21 eyes. Average ocular recession based on Hertel measurements was 3.6 mm and there were no surgical complications. New-onset or worsening diplopia was noted postoperatively in 2 of 11 subjects. However, in patients where both struts were preserved, there was zero incidence of postoperative diplopia (0/6). These results indicate that preservation of an inferomedial bony strut is not only technically feasible but also does not compromise the adequacy of decompression. The results also suggest that preservation of the inferomedial bony strut during endoscopic orbital decompression can reduce the incidence of postoperative diplopia.

Chi-Square Distribution↗

The fate of thymocytes labeled in vivo with CFSE.

The fate of thymic emigrants had so far been studied using a variety of markers, each of which had inherent limitations as to stability, toxicity, or selectivity. We describe a new technique which relies on the in vivo injection of CFSE, an esterified vital dye hitherto used at 80 times lower concentrations for in vitro cell labeling. We show that CFSE labels a representative sample of all thymocyte subsets and that these migrate at a rate of approximately 2-3 x 10(6) cells/day to peripheral lymphoid organs. We show that they enter lymph nodes at day 1 postinjection and stay for at least 21 days, whereas the turnover in the spleen is more rapid. We also show by immunohistochemistry, using peroxidase-labeled anti-FITC antibodies, that CFSE-labeled thymic emigrants are confined to T-dependent areas of peripheral lymphoid organs.

Animals↗

The multimedia CD ROM: an innovative teaching tool for endoscopic sinus surgery.

The recent explosive growth in the use of endoscopic techniques in the performance of surgical procedures has created an important need for educational materials on this subject. However, limitations of currently available teaching tools frustrate the user and hamper the teaching and spread of these procedures. To improve on currently available methods, we developed a CD ROM video atlas of techniques in endoscopic sinus surgery (ESS). The multimedia CD ROM video atlas combines the best features of the surgical atlas with conventional videotapes. The component steps of procedures in ESS are presented to the viewer as brief, individual video sequences, accompanied by narration and a text of the highlights of each procedure. The use of digital video allows the user to access the segment of interest directly, in the order of preference, without having to sift through the other segments, as with conventional videocassettes. An interface allows control over playback of the video, and sequences can be reviewed instantly. Storage capacity of the CD ROM allows up to 60 minutes of video to be stored on each disk. The CD ROM combines the best elements of currently available educational tools and may represent a new approach for medical education.

CD-ROM↗

Nasal response in subjects undergoing challenges by inhaling occupational agents causing asthma through the nose and mouth.

BACKGROUND: Subjects with occupational asthma (OA) often report nasal symptoms, but nasal reactions to inhalation challenges with occupational agents have not been well characterized. METHODS: Fifteen subjects with OA (eight due to high-molecular-weight agents--flour and guar gum--and seven due to isocyanates) underwent inhalational challenges using closed-circuit devices (dry particles for high-molecular-weight agents and gas generator for isocyanates) on two occasions, 2-4 weeks apart in a random fashion. On one occasion, they inhaled through the nose and, on another, through the mouth. The FEV1 was monitored for up to 8 h afterward, and symptoms were documented with a standardized questionnaire on nasal symptomatology, assessment of nasal resistance by rhinomanometry, and nasal lavage for the examination of cells and mediators. RESULTS: Inhaling through the mouth and through the nose: 1) yielded similar asthmatic responses (25+/-8% and 22+/-10% maximum changes in FEV1) 2) more than doubled the peak nasal symptoms and nasal resistance when the maximum daily response was compared with prechallenge results. This increase occurred on the days of inhalational challenges through the mouth and through the nose. There were some significant responses assessed by nasal lavage in terms of cells and mediators, again with no differences between the days of challenges through the mouth and through the nose. CONCLUSIONS: Inhaling occupational agents of high or low molecular weight, including isocyanates, whether through the mouth or nose: 1) results in a similar asthmatic response 2) causes a significant nasal response in terms of symptoms and an increase in nasal resistance 3) causes some significant changes in inflammatory cells and mediators.

Administration, Inhalation↗

Gelatinase B (MMP-9) production and expression by stromal cells in the normal and adult thymus and experimental thymic lymphoma.

Correlative and functional evidence support a crucial role for metalloproteinase (MMP) activity in tumor progression. Dysregulation of MMP production at local tumor sites is thought to participate in the remodeling of the local stromal tissue necessary for tumor growth. The extent of damages in local tissues is often reflected by the high concentration of MMP released in the bloodstream of cancer patients. The integrity of the thymic architecture plays a crucial role in the development of mature T cells, but it is compromised by extensive remodeling occurring during the development of thymic lymphomas. In the present work, we have used an experimental thymic lymphoma model to investigate the regulation of MMP-9 (gelatinase B) production in animals bearing large thymic lymphomas. We show a 3-fold increase in serum gelatinase B (Gel B) levels in animals bearing thymic lymphoma compared with those found in normal animals and a correlation between these levels and the size of the tumor. Although Gel B was found within the thymic tumor, lymphoma cells did not express it in vivo, indicating that Gel B expression was associated with thymic stromal cells rather than lymphoma cells. This was corroborated by evidence that lymphoma cells have the capacity to stimulate Gel B gene expression in stromal cells. Our results suggest that lymphoma cells can exert a significant control over Gel B expression by local stromal cells, thereby inducing the extensive remodeling necessary for tumor growth.

Animals↗

A practical guide for the diagnosis and treatment of acute sinusitis.

OBJECTIVE: To develop guidelines for the diagnosis and management of acute sinusitis. OPTIONS: Diagnostic clinical criteria and imaging techniques, the role of antimicrobial therapy and duration of treatment, and the role of adjunct therapy, including decongestants, glucocorticosteroids and nasal irrigation. OUTCOMES: Improved accuracy of clinical diagnosis, better utilization of imaging techniques and rational use of antimicrobial therapy. EVIDENCE: A MEDLINE search for relevant articles published from 1980 to 1996 using the MeSH terms "sinusitis," "acute sinusitis," "respiratory infections," "upper respiratory infections," "sinusitis" and "diagnosis," "sinusitis" and "therapy," "sinusitis" and "etiology," and "antimicrobial resistance" and search for additional articles from the reference lists of retrieved articles. Papers referring to chronic sinusitis, sinusitis in compromised patients and documented nonbacterial sinusitis were excluded. The evidence was evaluated by participants at the Canadian Sinusitis Symposium, field in Toronto on April 26-27, 1996. VALUES: A hierarchical evaluation of the strength of evidence modified from the methods of the Canadian Task Force on the Periodic Health Examination was used. Strategies were identified to deal with problems for which no adequate clinical data were available. Recommendations arrived at by consensus of the symposium participants were included. BENEFITS, HARMS AND COSTS: Increased awareness of acute sinusitis, accurate diagnosis and prompt treatment should reduce costs related to unnecessary investigations, time lost from work and complications due to inappropriate treatment. As well, physicians will be better able to decide which patients will not require antimicrobial therapy, thus saving the patient the cost and potential side effects of treatment. RECOMMENDATIONS: Clinical diagnosis can usually be made from the patient's history and findings on physical examination only. Five clinical findings comprising 3 symptoms (maxillary toothache, poor response to decongestants and a history of coloured nasal discharge) and 2 signs (purulent nasal secretion and abnormal transillumination result) are the best predictors of acute bacterial sinusitis (level I evidence). Transillumination is a useful technique in the hands of experienced personnel, but only negative findings are useful (level III evidence). Radiography is not warranted when the likelihood of acute sinusitis is high or low but is useful when the diagnosis is in doubt (level III evidence). First-line therapy should be a 10-day course of amoxicillin (trimethoprim-sulfamethoxazole should be given to patients allergic to penicillin) (level I evidence) and a decongestant (level III evidence). Patients allergic to amoxicillin and those not responding to first-line therapy should be switched to a second-line agent. As well, patients with recurrent episodes of acute sinusitis who have been assessed and found not to have anatomic anomalies may also benefit from second-line therapy (level III evidence). VALIDATION: The recommendations are based on consensus of Canadian and American experts in infectious diseases, microbiology, otolaryngology and family medicine. The guidelines were reviewed independently for the advisory committee by 2 external experts. Previous guidelines did not exist in Canada.

Acute Disease↗

Quantitative flow cytometric detection of specific microorganisms in soil samples using rRNA targeted fluorescent probes and ethidium bromide.

Specific detection and accurate enumeration of microorganisms in the environment have been hampered by the lack of suitable techniques. A three-parameter flow cytometric method (FCM) was developed to detect quantitatively Sphingomonas sp. strain 107 inoculated into soil samples. By combining light scattering profiles (i.e., morphological properties), ethidium bromide (EtBr) influx (i.e., wall permeability), and fluorescence in situ hybridization against the 16S rRNA (i.e., detection specificity), we could accurately discriminate the bacterium of interest from the indigenous microflora and soil debris. EtBr was used, first, to determine the optimal cell wall permeabilization treatment to allow oligonucleotide probes to enter the bacterial cells and, second, to achieve clear discrimination of fixed cells from debris in soil samples. This method allowed effective qualitative and quantitative analysis by fluorescence in situ hybridization. The results showed that the detection threshold by FCM was 3 x 10(4) cells/g of dry soil. Cell counts deduced from FCM analysis were similar to those obtained by the colony forming unit assay when soils contained fewer than 3 x 106 cells/g dry soil. This method should be useful for either quantitative monitoring of microorganisms inoculated in contaminated soil samples during bioremediation or detecting known bacterial strains in environmental samples.

Cell Separation↗

Treatment with hot, humid air reduces the nasal response to allergen challenge.

Ten subjects with asymptomatic seasonal allergy, outside of their allergy season, underwent allergen provocation following 1 hour of exposure to air at either 20 degrees C and 30% relative humidity (RH) or air at 37 degrees C and 90% RH. The ipsilateral changes following antigen challenge were compared under the two conditions. Conditioning of the nose to 37 degrees C, 90% RH reduced total histamine release (7.9 +/- 1.8 ng vs 4.2 +/- 1.3 ng; p < or = 0.05), sneezes (6 +/- 2 vs 3 +/- 1; p < or = 0.05), pruritus (score of 17.4 +/- 6.0 vs score of 2.0 +/- 1.8 out of a total score of 100, p < or = 0.01), nasal airway resistance (1.4 +/- 0.8 kPa/L/sec vs 0.2 +/- 0.1 kPa/L/sec; p < or = 0.05), human serum albumin levels (389.6 +/- 53.4 micrograms vs 242.2 +/- 37.9 micrograms; p < or = 0.05), and congestion (score of 23.8 +/- 4.8 vs score of 10.6 +/- 5.4 out of a total score of 100, p < or = 0.01). It had no effect on the volume of secretions (p = 0.8), lactoferrin levels (p = 0.3), or rhinorrhea (p = 1.0). Thus air at 37 degrees C and 90% RH partially reduces the early response to antigen. Its effects are greatest on histamine release, the vascular response, and neural responses, with no effect on the glandular response. The mechanisms underlying these effects are unknown.

Adult↗

Flow cytometric analysis of gelatinase B (MMP-9) activity using immobilized fluorescent substrate on microspheres.

Gelatinase B is a member of the metalloproteinase family of enzymes that degrade the extracellular matrix under normal and pathological conditions, including autoimmune diseases and tumor cell dissemination. In the present work, we describe a simple and reliable method that allows qualitative and quantitative measurements of a specific enzymatic reaction (mediated here by gelatinase B) by flow cytometry using fluorochrome-labeled substrate coated on polystyrene microspheres. Using this approach, proteolytic degradation can be monitored by the decrease of the fluorescence emitted by the microspheres following incubation with the enzyme. In most of the experiments, the signal-to-noise ratio between autofluorescent microspheres and those coated with the fluorescein isothiocyanate (FITC)-labeled substrate was near 500. This ratio allows one to measure accurately the enzymatic activity in the presence of chemical or biological inhibitors. FITC labeling and passive adsorption of substrates on the solid support did not cause significant conformational changes or steric hindrance that would interfere with the proteolytic activity of gelatinase B. This method constitutes a powerful tool for the measurement, on a routine basis, of the net activity resulting from the balance between the gelatinase B activity and the presence of natural inhibitors and for the identification of new metalloproteinase inhibitors that could suppress the excessive proteolytic activity that characterizes many disease processes.

Collagenases↗