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J Deschênes

Publications and source records attributed to J Deschênes.

At least 19 recordsLinked to original sources
PubMed2006

Low-dose inhaled and nasal corticosteroid use and the risk of cataracts.

Orally inhaled corticosteroid use has been convincingly linked to an increase in the risk of cataracts, although the risk at lower doses in common use remains uncertain. The potential risk of cataracts with the use of nasal corticosteroids is unknown. A matched nested case-control analysis was performed in a population-based cohort of elderly people who had been dispensed medications for airway disease, as identified through a universal drug benefit plan. Inhaled corticosteroid use was associated with a dose-related increase in both the risk of all cataracts and severe cataracts requiring extraction, and the increase in risk of severe cataracts was apparent even at daily doses of </=500 microg. An excess risk with nasal corticosteroids was not apparent for severe cataracts. It is concluded that, among the elderly, even low doses of inhaled corticosteroids are associated with a small but significant excess risk of cataracts requiring extraction. Such an excess risk was not observed with nasal corticosteroids.

Administration, Inhalation↗
PubMed2006

Ahmed valve implantation in glaucoma secondary to chronic uveitis.

PURPOSE: To evaluate the efficacy of Ahmed valve (AV) implantation in patients with uveitic glaucoma. METHODS: In total, 18 patients (19 eyes) with glaucoma secondary to chronic uveitis, who underwent AV implantation were retrospectively reviewed. Visual acuity, intraocular pressure (IOP), and glaucoma medications at the most recent examination prior to surgery, were compared with those of last postoperative examination. The surgical success was defined as IOP less than 21 mmHg and greater than 4 mmHg without loss of light perception and visually devastating complications at the last postoperative examination. Decrease in the number of glaucoma medications was also a criterion for surgical success. RESULTS: The mean follow-up period was 26+/-9.7 months. The mean preoperative and postoperative IOPs were 33.3+/-9.7 (range, 20-57) mmHg and 17.3+/-10.8 (range, 6-40) mmHg respectively (P<0.0001). The mean number of antiglaucoma medications was 3.5+/-0.8 (range, 2-5) preoperatively and 1.4+/-1.3 (range, 0-4) postoperatively (P<0.0001). Valve occlusion (five eyes, 26.3%) was the most commonly observed complication. Surgical success was achieved in 13 eyes (68.4%). The cumulative probability of success was 94.4% at 1 year and 60% at 2 years. Five eyes (26.3%) with IOP greater than 21 mmHg and one (5.3%) with corneal decompensation requiring penetrating keratoplasty were considered as failures. CONCLUSIONS: The implantation of AV is an effective surgical procedure for the management of uveitic glaucoma. The inflammatory background might contribute to the occurrence of valve occlusion, which is the most common complication. Prevention of this complication is an essential factor for improving the surgical outcome.

Adolescent↗
PubMed2004

Germline truncating mutations in both MSH2 and BRCA2 in a single kindred.

There has been interest in the literature in the possible existence of a gene that predisposes to both breast cancer (BC) and colorectal cancer (CRC). We describe the detailed characterisation of one kindred, MON1080, with 10 cases of BC or CRC invasive cancer among 26 first-, second- or third-degree relatives. Linkage analysis suggested that a mutation was present in BRCA2. DNA sequencing from III: 22 (diagnosed with lobular BC) identified a BRCA2 exon 3 542G>T (L105X) mutation. Her sister (III: 25) had BC and endometrial cancer and carries the same mutation. Following immunohistochemical and microsatellite instability studies, mutation analysis by protein truncation test, cDNA sequencing and quantitative real-time PCR revealed a deletion of MSH2 exon 8 in III: 25, confirming her as a double heterozygote for truncating mutations in both BRCA2 and MSH2. The exon 8 deletion was identified as a 14.9 kb deletion occurring between two Alu sequences. The breakpoint lies within a sequence of 45 bp that is identical in both Alu sequences. In this large BC/CRC kindred, MON1080, disease-causing truncating mutations are present in both MSH2 and BRCA2. There appeared to be no increased susceptibility to the development of colorectal tumours in BRCA2 mutation carriers or to the development of breast tumours in MSH2 mutation carriers. Additionally, two double heterozygotes did not appear to have a different phenotype than would be expected from the presence of a mutation in each gene alone.

Adult↗
PubMed2003

Ultrasound biomicroscopic evaluation of the traumatized eyes.

PURPOSE: To review causes for performing an ultrasound biomicroscopic (UBM) examination in traumatized eyes, to present common UBM findings of 109 eyes with a history of ocular trauma and to compare these findings according to the type of the trauma. MATERIALS AND METHODS: A total of 109 eyes with a history of mechanical ocular trauma, which underwent an UBM examination between December 1996 and April 2002, were evaluated retrospectively. All cases were classified according to the criteria of the Ocular Trauma Classification Group and UBM findings were reviewed. For statistical ana- lyses, chi(2) test and Fisher's exact test were used. RESULTS: UBM examinations were performed for the evaluation of the zonules before cataract surgery (49.5%), examination of the anterior segment in the presence of media opacities (32.1%), detection of suspected ocular foreign bodies (10.1%) and the evaluation of ocular hypotony (8.3%). In all, 67 eyes (61.5%) had a closed-globe injury, whereas 42 (38.5%) had an open-globe injury. The most common UBM findings in a closed-globe injury were zonular deficiency (64.2%), angle recession (43.3%), iridodialysis (17.9%), and dislocated lens (16.4%). The most common UBM findings in an open-globe injury were zonular deficiency (54.8%), iridodialysis (26.2%), peripheral anterior synechiae (PAS) (26.2%), and iridocorneal adhesion (19%). Among the common UBM findings, the angle recession was significantly higher (P<0.001) in closed-globe injury group and PAS formation was significantly higher (P<0.05) in open-globe injury group. CONCLUSIONS: UBM is particularly superior to other methods in the evaluation of the zonular status, angle recession, cyclodialysis, and the detection of small superficial and intraocular foreign bodies.

Adolescent↗
PubMed2001

Prevalence of founder BRCA1 and BRCA2 mutations in unselected French Canadian women with breast cancer.

The frequency of BRCA1 and BRCA2 mutations in women with breast cancer varies according to the age at diagnosis, family history of cancer, and ethnicity/country of origin. We set out to estimate the frequency of seven previously described founder mutations in BRCA1 and BRCA2 in all eligible French Canadian women diagnosed with invasive breast cancer at one Montreal hospital over a 20-month period. One hundred and ninety-two patients were eligible and 127 (66.2%) provided blood for genetic testing. We identified 4 women who carried a founder mutation (3.1%, 95% confidence interval 0.9-7.9%) in this population. Interestingly, all the mutations were in BRCA2. The mean age at diagnosis for mutation carriers was 51.2 years (range 49.1-53.5). Two of these 4 cases were lobular invasive carcinomas and 2 were ductal carcinomas, histological grade 1 or 2. Despite a small tumor size (< or =20 mm), axillary nodal involvement was present in 3 women. Estrogen receptors were strongly expressed in all cases. Two of the 4 cases reported a strong family history of breast cancer, but a family history of site-specific breast cancer was a relatively poor indicator of the presence of BRCA2 mutations. The absence of BRCA1 mutations may be a result of chance, but may also reflect different geographical origins of the most common BRCA1 mutations within the French Canadian population.

Adult↗
PubMed2000

Agonistic induction of a covalent dimer in a mutant of natriuretic peptide receptor-A documents a juxtamembrane interaction that accompanies receptor activation.

The natriuretic peptide receptor-A (NPR-A) is composed of an extracellular domain with a ligand binding site, a transmembrane-spanning domain, a kinase homology domain, and a guanylyl cyclase domain. In response to agonists (atrial natriuretic peptide (ANP) and brain natriuretic peptide), the kinase homology domain-mediated guanylate cyclase repression is removed, which allows the production of cyclic GMP. Previous work from our laboratory strongly indicated that agonists are exerting their effects through the induction of a juxtamembrane dimeric contact. However, a direct demonstration of this mechanism remains to be provided. As a tool, we are now using the properties of a new mutation, D435C. It introduces a cysteine at a position in NPR-A corresponding to a supplementary cysteine found in NPR-C6, another receptor of this family (a disulfide-linked dimer). Although this D435C mutation only leads to trace levels of NPR-A disulfide-linked dimer at basal state, covalent dimerization can be induced by a treatment with rat ANP or with other agonists. The NPR-A(D435C) mutant has not been subjected to significant structural alterations, since it shares with the wild type receptor a similar dose-response pattern of cellular guanylyl cyclase activation. However, a persistent activation accompanies NPR-A(D435C) dimer formation after the removal of the inducer agonist. On the other hand, a construction where the intracellular domain of NPR-A(D435C) has been truncated (DeltaKC(D435C)) displays a spontaneous and complete covalent dimerization. In addition, the elimination of the intracellular domain in wild type DeltaKC and DeltaKC(D435C) is associated with an increase of agonist binding affinity, this effect being more pronounced with the weak agonist pBNP. Also, a D435C secreted extracellular domain remains unlinked even after incubation with rat ANP. In summary, these results demonstrate, in a dynamic fashion, the agonistic induction of a dimeric contact in the juxtamembrane domain of NPR-A. In addition, this process seems to require membrane attachment of the receptor. Finally, the intracellular domain represses this contact at the basal state, showing its potent influence on the outer juxtamembrane domain.

Amino Acid Sequence↗
PubMed2000

Contrast and glare testing in the assessment of visual performance of candidate eyes for penetrating keratoplasty.

PURPOSE: To determine whether visual acuity (VA) measurements performed at low levels of contrast and glare are a better diagnostic tool for determining whether corneal clouding warrants surgery. METHODS: Fifty-nine subjects were recruited from among the candidates for corneal graft. Monocular VA was measured with three Regan contrast VA charts: 96, 25, and 11%, with and without glare provided by the Brightness Acuity Tester (BAT). The discriminative ability of the tests was estimated using the area (AR) under receiver operating characteristic (ROC) curves. Associations between the different VA tests and the Visual Function Index (VF-14) score were studied, using Spearman coefficients. RESULTS: When comparing candidate eyes with contralateral eyes with corneal disease, lower contrasts VA tests provided greater discriminative power. VA measurements made with glare also tended to provide greater discrimination. In fact, discrimination was best with 11% contrast VA with glare, but "testability" was poor. The most practical test in a clinical setting, which retained high discriminative ability (0.798), was the 25% contrast VA with glare. The eye with the best VA correlated strongly with the VF-14, especially at 25% contrast without glare, resulting in an Rs of -0.729. CONCLUSION: Twenty-five percent contrast VA with BAT could help the practitioner to decide whether a corneal transplant is warranted when symptoms of reduced vision are more important than what high-contrast VA might indicate.

Adult↗
PubMed2000

[Therapeutics for future treatment of uveitis].

The increased knowledge in immunology and the progresses of pharmacology have improved our treatment of autoimmune diseases. The main anti-inflammatory effects of corticosteroids are an attenuation of the hypersensibility reactions, a sequestration of intravascular lymphocytes and an inhibition of the production of cytokines and eicosanoids. The non-steroidal anti-inflammatory drugs (NSAID's) form another group of medications particularly useful for the treatment of chronic uveitis. Several Cox-2 inhibitory medications are at the moment under clinical investigation and some are commercially available. One of their characteristics is to present less of the most undesirable side effects seen with conventional NSAID's like irritation of the gastro-intestinal tractus and platelets aggregation inhibition. Agents like cyclophosphamide, leukeran, imuran, methotrexate and cyclosporin have been used extensively for the treatment of severe uveitis. Because of its efficacy and safety, methotrexate is the best immunosuppressive agent to be tried for the treatment of chronic uveitis. However, immunosuppressive treatments and corticosteroids have many side effects and are not very selective. To improve our therapeutic arsenal, other treatments are being investigated for the treatment of severe uveitis. Manipulations of cytokines expression by Th1 lymphocytes will be one of then.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

The VF-14 index of functional visual impairment in candidates for a corneal graft.

PURPOSE: To validate the Visual Function-14 (VF-14) index of functional visual impairment in candidates for a corneal graft. METHODS: One hundred thirty-four patients who were candidates for a corneal graft participated in this study between August 1996 and February 1997. Demographic, ocular history, best-corrected visual acuity, and detailed ocular examination data were collected. Functional visual impairment information was obtained by telephone interviews using the following: VF-14, SF-36 (Short Form-36, a more generic measure of general health function), and Visual Symptom Score, and four questions measuring the overall amount of trouble with vision, dissatisfaction with vision, ocular pain, and discomfort. RESULTS: The average age of corneal graft candidates was 64 +/- 18 years (range, 18 to 90 years) and 60% were women. The most frequent corneal disease was pseudophakic bullous keratopathy (41%). Ocular comorbidities included glaucoma or ocular hypertension (30%) and cataract (19%). The mean best-corrected visual acuity of the eye scheduled for surgery was 1.33 +/- 0.56 logMAR whereas the best eye best-corrected visual acuity was 0.36 +/- 0.44 logMAR. The mean VF-14 score was 73% +/- 26%, and the internal consistency was high, with a Cronbach alpha value of 0.94. The VF-14 correlated strongly with the best eye best-corrected visual acuity. It also correlated strongly with the Visual Symptom Score, the global measures of trouble and dissatisfaction with vision. Candidates for a corneal graft had low scores for all eight general health concepts evaluated with the SF-36, and the VF-14 correlated with seven of the eight SF-36 subscales. CONCLUSION: The VF-14 is a valid measure of functional visual impairment in candidates for a corneal graft. The Visual Symptom Score and the SF-36 are also useful indices in such patients.

Adolescent↗
PubMed1998

Determinants of rifabutin-associated uveitis in patients treated with rifabutin, clarithromycin, and ethambutol for Mycobacterium avium complex bacteremia: a multivariate analysis. Canadian HIV Trials Network Protocol 010 Study Group.

Uveitis occurred in a substantial proportion of AIDS patients receiving rifabutin, 600 mg daily, together with clarithromycin and ethambutol for treatment of Mycobacterium avium complex bacteremia. A case-control study was undertaken to examine potential risk factors for developing uveitis. Of eight parameters examined, only baseline body weight predicted the development of uveitis by both univariate and multivariate analyses (P = .001). The incidence of uveitis was 14% in patients weighing >65 kg, 45% in patients between 55 and 65 kg, and 64% in patients <55 kg. Concomitant therapy with fluconazole, a drug known to raise serum rifabutin concentrations, was not associated with an increased incidence of uveitis. The risk of uveitis was markedly reduced when rifabutin was given at 300 mg daily in combination with clarithromycin and ethambutol.

AIDS-Related Opportunistic Infections↗
PubMed1998

The immunology of corneal graft rejection.

Corneal transplantation is the most successful of organ transplants due to the fact that the eye is an immunologically privileged site, and the cornea is an immunologically privileged tissue. The factors responsible for this include presence of the blood-aqueous barrier, the avascularity of the cornea, the absence of classic antigen-presenting cells (APCs) in the central cornea, inhibitory factors in the aqueous humor, the phenomenon known as anterior chamber-associated immune deviation (ACAID), and the intraocular expression of Fas ligand. Loss of ocular immune privilege can occur with breaching of the blood-ocular barrier, corneal neovascularization, migration of classic APCs to the center of the cornea, loss of inhibitory factors in aqueous humor, abrogation of ACAID, and loss of Fas ligand expression within the anterior chamber. The purpose of this review is to analyze these events and how they relate to corneal graft rejection. A discussion on future research and therapeutic modalities is provided.

Animals↗
PubMed1997

Cyclosporine monitoring with levels 6 hours after the morning dose in patients with noninfectious uveitis.

PURPOSE: The authors evaluate whether monitoring of cyclosporine blood levels 6 hours after the morning dose (T6), as opposed to trough (T0), could reduce the incidence of side effects. METHODS: Cyclosporine dose adjustments were performed based on blood cyclosporine T6 enzyme-multiplied immunologic technique, irrespective of T0 and serum creatinine (SCr), in eight steroid- or azathioprine-resistant uveitis patients. The cyclosporine dose was adjusted to achieve a cyclosporine T6 level of 150 to 250 ng/ml. RESULTS: All patients improved clinically over 16 +/- 10 months. The mean dose of cyclosporine was 3.9 +/- 1.4 mg/kg/day. In 149 visits (47%), 70 dose adjustments were made. Initial and final SCr, potassium, magnesium, and uric acid serum levels and systolic/diastolic blood pressure measurements were not statistically different. There was no change in the creatinine clearance, glomerular filtration rate, or the effective renal plasma flow performed before starting T6 monitoring and at 13 +/- 8 months of follow-up. CONCLUSIONS: Cyclosporine monitoring according to T6 levels is associated with optimal immunosuppression and stable renal function in patients with noninfectious uveitis.

Adult↗
PubMed1997

Cyclosporine dose adjustment using levels obtained six hours after the morning dose: effect on side effects in patients with autoimmune diseases.

Cyclosporine (CsA) is frequently used for nontransplant indications such as autoimmune diseases. Unfortunately, side effects such as renal dysfunction and hypertension are frequently described in spite of close monitoring with CsA trough levels. The purpose of the present prospective cohort study was to use the CsA level obtained 6 h after the morning dose (T6) for CsA dose adjustment and its impact on observed side effects in 11 patients (44+/-17 years) treated with CsA for autoimmune diseases. Patients were monitored for CsA-related side effects at each outpatient visit, including blood pressure measurement, CsA trough and T6 levels and routine laboratory tests. Changes in blood pressure and biochemical parameters were compared to the previous visit (n = 244) and a change >30% was considered significant. Significant changes in monitored variables were observed in the following percentage of visits: increases in systolic/diastolic blood pressure (1.2), serum creatinine (6.1), potassium (0.8), and uric acid (6.3), and a decrease in magnesium (0.5). At the end of follow-up (20+/-12.5 months), CsA dose was reduced from 4.8+/-1.1 to 3.5+/-1 mg/kg/day (p = 0.004); serum creatinine, potassium, uric acid, hemoglobin, total cholesterol, effective renal plasma flow and glomerular filtration rate did not differ from baseline. Alkaline phosphatase increased from 63+/-19 to 82+/-21 U/l(p = 0.04) and magnesium decreased from 0.85+/-0.1 to 0.75+/-0.1 mmol/l (p = 0.02). Transient hypertension and reversible renal dysfunction was seen in 2 patients, respectively. In conclusion, CsA monitoring according to T6 levels may allow a lower CsA dose than the one usually recommended and reduce the incidence of side effects in patients with autoimmune diseases.

Adult↗