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Hamilton Dr. Don Whelan Department of Paediatrics & Human Genetics McMaster University Medical Centre 1200 Main Street West Hamilton, ON L8N 3Z5 Co-ordinator: Debbie Eisenberg Tel: 905 ; 521-5085 Fax: 905 ; 521-2651 Kingston Dr. Mohamed Khalifa Division of Medical Genetics Department of Paediatrics Queen's University 20 Barrie Street Kingston, ON K7L 3N6 Co-ordinator: Ruth Lokkesmoe Tel: 613 ; 545-6310 Fax: 613 ; 548-1348.
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Although Wnt -catenin stimulation promotes in general an increase in NR gene activation, an equally conserved theme is the ability of NRs and their agonists to promote transrepression of the Wnt -catenin Tcf pathway Fig. 3A ; . This trend is observed not only by in vitro assays but also in vivo, thus suggesting that NRs and endocrine pathologies harboring activated Wnt -catenin signaling may be subject to therapeutic manipulation. Importantly, an increasing number of agonistic and antagonistic synthetic ligands are being identified that may influence the inhibitory actions that NRs appear to confer upon Wnt signaling. The modes are diverse and, in many cases, cell line dependent; however, it is clear that NRs have the potential for potent repression of Wnt -catenin Tcf signaling Table 2.
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Rate, and body position. Patients found to have OSA then underwent an unattended CPAP titration using an auto-titrating CPAP device. After 30 days of treatment, the questionnaires and PVT were repeated. Statistical analyses were performed and statistical significance was defined as 2-tail alpha value of 0.05. Primary outcomes measured were CPAP use and PVT scores. Subjective measures included perception of treatment efficacy 6-point Likert scale ; , sleepiness by ESS scores, and QOL by SF-36. Results : Fourteen male subjects, age 37-75 years mean 48.57, S.D. 9.83 ; completed the study. Apnea Hypopnea Index before treatment was 44.62 events per hour S.D. 24.13 ; . Quality of life as measured by SF-36 improved significantly for physical health, general health, vitality, social functioning, emotional and mental health subscales. Physical function trended towards improvement. Epworth scores improved from 13.21 S.D.4.08 ; to 5.57 S.D. 3.78 ; after treatment. Compliance was available for 8 subjects with mean use of 4.04 hours nightly range 0 - 7.45 hrs ; . PVT pretreatment mean 351.05, S.D. 175.94; posttreatment mean 304.58, S.D. 102.53 ; showed a trend towards improvement Conclusion : In selected patients, ambulatory management of obstructive sleep apnea improved the patient's QOL. These improvements are comparable to previously published results using traditional in-laboratory management. Support optional ; : This study received support by the ResMed Research Foundation, for example, avodart effect side.
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P226 ADULT-ONSET, FEMALE GENDER AND GOITER: RISK FACTORS FOR THE DEVELOPMENT OF AUTOIMMUNE THYROID DISEASE IN TYPE 1 DIABETES MELLITUS PATIENTS Zantut-Wittmann D.E., Pavin E.J., Costa A.M.J., Parisi M.C.R. Endocrinology, Department of Internal Medicine; School of Medical Sciences, State University of Campinas, So Paulo, Brazil Introduction: Autoimmune thyroid disease ATD ; , mainly hypothyroidism, is often associated with type 1 diabetes mellitus DM1 ; . Detection of risk factors for ATD and precocious specific hormonal therapy to thyroid dysfunction can avoid the impairment of metabolic control of DM1, lowered basal metabolism and dyslipidemia. Patients and methods: We are evaluated clinical and laboratory thyroid function, presence of anti-thyroid antibodies ATA ; , distribution of sex and age of beginning of DM1 in 115 patients. The control group consisted of 83 individuals clinical and laboratory euthyroid, without goiter. Results: ATA was positive in 24.3% of DM1 patients vs. 1.2% of control group, and it was more frequent in diabetic females. Anti-thyroperoxidase antibody TPOAb ; was present in 96.4% of ATA positive patients. Thyroid dysfunction was found in 71.4% of these patients: overt primary hypothyroidism 53.6% ; , subclinical hypothyroidism 14, 3% ; and Basedow-Graves' disease 3.6% ; . 15 115 diabetic patients had goiter, 13 with ATA positive and thyroid dysfunction. ATA frequency was higher in adult-onset DM1 when comparing with the classic form 53.5% vs 20% ; . The logistic regression regarding presence of ATA demonstrated influence of adult age of DM1 onset odds ratio, OR 4.84 female gender OR 4.4 ; and goiter OR 41.2 ; . This analysis for thyroid dysfunction verified influence of TPOAb OR 21.0 ; , adult-onset of DM1 OR 6.06 ; , female gender OR 14.8 ; and goiter OR 16.84 ; .Conclusions: Laboratory assessment of thyroid function and ATA detection should be included in routine investigations in DM1 patients. Female gender, adult-onset, goiter and TPOAb account to a higher risk of Hashimoto's thyroiditis when DM1 is present. P227 UPREGULATION OF PEROXIREDOXINS, ADIPONECTIN AND PPAR IN MUSCULAR CELLS IN THYROID ASSOCIATED ORBITOPATHY: A PROTECTIVE MECHANISM AGAINST OXIDATIVE STRESS? Senou M. 1 ; , Delaigle A. 2 ; , Daumerie Ch. 3 ; , Boschi A. 4 ; , Spiritus M. 4 ; , Mahy P. 5 ; , Knoops B. 6 ; , Brichard S. 2 Many M.C. 1 ; Experimental Morphology Unit 1 Endocrinology and Metabolism Unit 2 Endocrinology Department 3 Ophthalmology Department 4 Maxillo-facial Surgery Department 5 Cell Biology Unit 6 ; , Universit Catholique de Louvain, Bruxelles, Belgium In thyroid associated orbitopathy TAO ; , the volume of the muscles and of the adipose tissue is increased, adipogenesis being associated to an upregulation of several genes ie. adiponectin ApN ; and PPAR Kumar et al, 2005 ; . We have studied more extensively the muscular cells, in order to verify their integrity and to localize ApN, PPAR and peroxiredoxins PRDXs ; known as antioxidant enzymes. Extraocular muscles were obtained from 21 TAO patients and 19 controls with strabismus. They were processed for morphology, immunodetection of caspase-6, PRDX5, ApN and PPAR and measurement by RTQ-PCR of PRDX5, ApN and PPAR mRNA levels. Immunodetection of these proteins was also done on orbital adipose tissues from TAO patients n 9 ; and controls n 9 ; operated on for fracture. In TAO, the muscular cells were dissociated by fibrous tissue and adipocytes often near mast cells. Activated caspase-6 was detected in the nuclei of numerous TAO muscular cells, indicating an oxidative stress and apoptosis. PRDX5 expression was also strongly increased in TAO muscular cells. ApN was highly expressed inside the TAO muscular and endothelial cells. A significant ApN increase 5 fold, p 0.0132 ; was demonstrated by RTQ-PCR in the muscles from TAO patients. PPAR was also upregulated in TAO with an intense nuclear labelling in numerous muscular cells and this was confirmed by RTQ-PCR 4.5 fold, p 0.0106 ; . The expression of PRDX5, ApN and PPAR was also increased in orbital adipocytes from TAO patients versus controls. In conclusion TAO induces an oxidative stress to muscular cells leading to apoptosis, but the upregulation of the antioxidant enzyme, PRDX5, allows cell protection. The upregulation of ApN and PPAR in the muscular cells themselves could also be viewed as a protective mechanism against deleterious inflammatory reaction and oxidative stress, as it has been recently shown in skeletal muscles of type 2 diabetic mice Delaigle et al., 2006.
Table II. Oligonucleotide primer sequences used Gene RPLP0 AR ER ER DNMT1 ARA70 PSA PAP Oligonucleotide Upper primer Lower primer Upper primer Lower primer Upper primer Lower primer Upper primer Lower primer Upper primer Lower primer Upper primer Lower primer Upper primer Lower primer Upper primer Lower primer Upper primer Lower primer Sequence 5 -GGC GAC CTG GAA GTC CAA CT-3 -CCA TCA GCA CCA CAG CCT TC-3 -CCT GGC TTC CGC AAC TTA CAC-3 -GGA CTT GTG CAT GCG GTA CTC A-3 -CCA CCA ACC AGT GCA CCA TT-3 -GGT CTT TTC GTA TCC CAC CTT TC-3 -AGA GTC CCT GGT GTG AAG CAA G-3 -GAC AGC GCA GAA GTG AGC ATC-3 -CGC GCT CTA CCC TGC ACT C-3 -TGA ATC CGG CCT CAG GTA GTT-3 -TAC CTG GAC GAC CCT GAC CTC-3 -CGT TGG CAT CAA AGA TGG ACA-3 -ACA ATT ACT CTG CGC CAG ACC A-3 -GCT GAA CTA GCA TGA GCC ATC AA-3 -ACC AGA GGA GTT CTT GAC CCC AAA-3 -CCC CAG AAT CAC CCG AGC AG-3 -CAT CTG GAA TCC TAT CCT ACT CTG-3 -AGT TCT TGA AAA CGA GGG CA-3 PCR product size bp ; 149 168 108 Table III. Relationship between AR mRNA level and the standard clinical and pathological factors Total population % ; AR mRNA level [no. of patients % ; ] Underexpression Total Age 50 Menopausal status Pre-menopausal Post-menopausal Histological gradeb I II III Lymph node status Node-negative Node-positive Macroscopic tumor sizec 30 mm 30 Relapses 131 100.0 ; 39 29.8 ; 92 70.2 ; 45 34.3 ; 86 65.7 ; 76 62.3 ; 46 37.7 ; 49 37.4 ; 82 62.6 ; 90 72.6 ; 34 27.4 ; 47 35.9 ; 84 64.1.
Stir bar sorptive extraction SBSE ; is an innovative sample extraction technique that can be used to process blood, urine, and tissue samples for routine drug screening in the forensic toxicology laboratory. The GERSTEL TDU System is a multifunctional thermal desorption unit capable of determining the presence of analytes from liquid samples after extraction using the TwisterTM stir bar. The TDU desorption system was evaluated for use in combination with GC MS for determining the presence of basic drugs in forensic samples. Human blood fortified with known quantities of drugs was used to evaluate sample diluents, extraction time, injection parameters and recovery. Case specimens containing drugs typically encountered in forensic samples were evaluated using the desorption method and compared with a liquidliquid extraction method followed by GC MS analysis. This evaluation demonstrated that the TDU desorptive method worked equally as well as the routine extraction method for the detection of basic drugs in screening forensic samples. In addition, the described technique avoids the use of extraction solvents and the subsequent centrifugation.
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Many patients develop AF asymptomatically, and only present to medical care when complications such as stroke or heart failure occur. One study reported that in patients with paroxysmal AF, only 1 in 12 paroxysms appeared to be symptomatic59. Consequently, cases of AF are often detected, particularly in the elderly, during a general practice visit for an unrelated problem. The elderly, as a group, have a high morbidity from stroke, thromboembolism and impaired cognitive function. It is not known whether asymptomatic AF per se is a potential risk factor for stroke. It is currently not clear how best to manage patients with asymptomatic AF, either in relation to treatment using a rate control or a rhythm control strategy, nor in terms of the need for antithrombotic therapy. 11.4.1. Methodological Introduction.
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Smith, et al. 2004: 235 ; found that carers lacked the knowledge and skills to care for stroke survivors within their homes in Scotland. They also found that carers were inadequately prepared for the caring role. This followed an earlier study by Kerr and Smith 2001: 428 ; , which suggested that carers of stroke victims did not receive adequate preparation prior to hospital discharge. It appears that despite the acknowledgement of carers within the health care system of developed countries, the needs with regard to preparing to care 4.4.3 ; remain unchanged.
The pharmacokinetic parameters of both groups in serum were as follows: 1 ; mean peak plasma concentration of 91 + - micrograms ml 25 mg ; and 24 + - 12 micrograms ml 25 mg twice 2 ; elimination half-lives of 48 + - 09 hours 25 mg ; and 64 + - 27 hours 25 mg twice and 3 ; the area under the plasma concentration curve of 09 + - micrograms.
Histamine skin reactions induced one hour later. results are presented in Table 2. Both compounds the histamine skin reaction and when show an additive effect. In the allergen given test.
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