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David Gillis

Publications and source records attributed to David Gillis.

18 recordsLinked to original sources
PubMed2006

Short course of systemic corticosteroids in sinonasal polyposis: a double-blind, randomized, placebo-controlled trial with evaluation of outcome measures.

BACKGROUND: Topical and systemic corticosteroids are the first choice in medical treatments for sinonasal polyposis, but surprisingly, there is no high-level evidence for the efficacy of oral corticosteroids. OBJECTIVE: The aim of this study was to establish the efficacy of a short course of oral prednisolone in ameliorating the symptoms of sinonasal polyposis, as well as reducing mucosal inflammation assessed by means of nasendoscopy and magnetic resonance imaging (MRI). A secondary aim was to evaluate the relationship between outcome measures. METHODS: Subjects with symptomatic endoscopically diagnosed sinonasal polyposis received 50 mg of prednisolone daily for 14 days or placebo. Outcome was quantified by using the modified 31-item Rhinosinusitis Outcome Measure questionnaire, physician's assessment, nasendoscopy with photography, and MRI. RESULTS: There were 20 subjects in each treatment group. Only the prednisolone-treated group showed significant improvement in nasal symptoms (P < .001). The Rhinosinusitis Outcome Measure score improved in both groups, but the prednisolone-treated group had significantly greater improvement than the placebo group (P < .001). Objectively, there was significant reduction in polyp size, as noted with nasendoscopy (P < .001) and MRI (P < .001), only in the prednisolone-treated group. The outcome measures correlated with each other; the highest level of correlation was between the objective measures of nasendoscopy and MRI (R(2) = 0.76, P < .001). There were no significant adverse events. CONCLUSION: This trial clearly establishes clinically significant improvement in the symptoms and pathology of sinonasal polyposis with a short course of systemic corticosteroids. MRI scanning and quantitative nasendoscopic photography are objective and valid tools for assessing the outcome of treatment in this condition. CLINICAL IMPLICATIONS: A 14-day course of 50 mg of prednisolone is safe and effective therapy for symptomatic nasal polyposis.

Adult↗
PubMed2006

Long-term immunity in young adults after a single dose of inactivated Hepatitis A vaccines.

We evaluated in a prospective study the immune response of naïve subjects to a single dose of inactivated Hepatitis A vaccine. Ninety-seven percent of the vaccinees sero-converted 1 month after vaccination and 93% were still positive 2 years later. All of the vaccinees had a strong booster response 2 years after the single dose. Avaxim was more immunogenic than Vaqta for the primary dose (p = 0.01 for sero-positivity, p<0.001 for antibody level) but no differences were found after boosting with Avaxim. Performance of intense physical activity during the first month after a single vaccine dose was associated with lower antibody levels (p = 0.004). This study indicates that a single dose of inactivated HAV vaccine elicits protective immune memory for at least 2 years.

Adolescent↗
PubMed2005

Noonan syndrome type I with PTPN11 3 bp deletion: structure-function implications.

Noonan syndrome was recently reported to be caused by mutations in the PTPN11 gene in 40% of the cases. This gene encodes the nonreceptor-type protein tyrosine phosphatase SHP-2 and has been shown to be self down-regulated with the concurrency of two SH2 domains. Insertion of a specific loop (D'EF) from N-terminal SH2 domain into the SHP-2 active-site is responsible for the reversible inhibition of the phosphatase activity. Here we report the first in frame trinucleotide deletion resulting in the removal of Aspartate 61 (D61del), a key residue of the N-terminal SH2 D'EF loop. Energetic-based structural analysis and electrostatic calculations carried out on the wild-type and mutant proteins predict lower stability of the D'EF loop for the D61del variant as compared to the wild type indicating better access to the active site and most likely an enzyme activated for longer extent. Similar computations were performed on the previously functionally characterized gain-of-function D61Y mutant and similar behaviors were observed. The simulation data for the D61del and D61Y mutants suggest that both variants could yield more catalytic cycles than the wild-type molecule in the same timespan because of the opening of the active site. It also supports the notion that D61 plays a major role for proper down-regulation of the protein tyrosine phosphatase activity of SHP-2.

Adult↗
PubMed2005

Development of consensus guidelines for anticardiolipin and lupus anticoagulant testing.

Interlaboratory and intermethod variation in commercial and in-house tests used for the measurement of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) limit the diagnostic value of the results from these tests. This short review summarizes published and unpublished guidelines (some developed using consensus procedures) on aCL and LA testing that are aimed at decreasing assay variation.

Antibodies, Anticardiolipin↗
PubMed2005

The histrelin implant: a novel treatment for central precocious puberty.

OBJECTIVE: Standard treatment of central precocious puberty (CPP) consists of intramuscular or subcutaneous administration of a gonadotropin-releasing hormone (GnRH) agonist (GnRHa) at 3- to 4-week intervals. Although generally effective in suppressing clinical and laboratory parameters of puberty, GnRHa injections are painful, and the need for monthly clinic visits may contribute to poor compliance. Recently, a subcutaneous implant was developed that releases the GnRHa histrelin at an average rate of 65 microg/day. The aims of this study were to determine if a histrelin implant would suppress gonadotropin and estradiol (E2) in girls with CPP for 1 year and to compare the suppression to standard treatment. METHODS: We studied 11 girls with CPP to determine if the histrelin implant can maintain long-term gonadotropin suppression. Mean age at diagnosis was 6 years (range: 2-9 years). GnRH (100 microg intravenously) stimulation tests (GnRH-STs) showed peak luteinizing hormone and follicle-stimulating hormone responses of 23 +/- 28 (mean +/- SD) and 20 +/- 25 mIU/mL, respectively. All subjects were initially treated with depot intramuscular GnRHa triptorelin embonate. Implants were inserted subcutaneously under local anesthesia, and depot GnRHa treatment was discontinued. Six girls were followed for 15 months after insertion (group A). For the remaining 5 girls, the implant was removed after 9 months, and a new implant was inserted at the same incision site (group B). GnRH-STs were performed before depot GnRHa treatment, immediately before implant insertion, at the 6- and 9-month visits for each patient and the 12- and 15-month visit for those girls followed for 15 months. RESULTS: In all girls, breast development regressed, growth velocity decreased, and bone-age advancement was slowed. Basal gonadotropins and their responses to GnRH-STs and E2 levels were suppressed. Peak luteinizing hormone and follicle-stimulating hormone responses to GnRH-STs at preinsertion versus 9 months were 1.30 +/- 1.34 vs 0.25 +/- 0.08 and 1.68 +/- 1.08 vs 1.13 +/- 0.55 mIU/mL, respectively. Basal and stimulated gonadotropin levels and E2 level remained suppressed in all 6 patients followed for 15 months after implant insertion. Patients and parents reported less pain and discomfort and less interference with school activity and work with the implant compared with standard monthly injections. CONCLUSIONS: The histrelin implant consistently suppresses clinical and laboratory parameters of puberty for 1 year and is a promising new technique for treating CPP without the pain and inconvenience of monthly injections.

Child↗
PubMed2004

Clinical inhibition of CYP2D6-catalysed metabolism by the antianginal agent perhexiline.

AIMS: Perhexiline is an antianginal agent that displays both saturable and polymorphic metabolism via CYP2D6. The aim of this study was to determine whether perhexiline produces clinically significant inhibition of CYP2D6-catalysed metabolism in angina patients. METHODS: The effects of perhexiline on CYP2D6-catalysed metabolism were investigated by comparing urinary total dextrorphan/dextromethorphan metabolic ratios following a single dose of dextromethorphan (16.4 mg) in eight matched control patients not taking perhexiline and 24 patients taking perhexiline. All of the patients taking perhexiline had blood drawn for CYP2D6 genotyping as well as to measure plasma perhexiline and cis-OH-perhexiline concentrations. RESULTS: Median (range) dextrorphan/dextromethorphan metabolic ratios were significantly higher (P < 0.0001) in control patients, 271.1 (40.3-686.1), compared with perhexiline-treated patients, 5.0 (0.3-107.9). In the perhexiline-treated group 10/24 patients had metabolic ratios consistent with poor metabolizer phenotypes; however, none was a genotypic poor metabolizer. Interestingly, 89% of patients who had phenocopied to poor metabolizers had only one functional CYP2D6 gene. There was a significant negative linear correlation between the log of the dextrorphan/dextromethorphan metabolic ratio and plasma perhexiline concentrations (r(2) = 0.69, P < 0.0001). Compared with patients with at least two functional CYP2D6 genes, those with one functional gene were on similar perhexiline dosage regimens but had significantly higher plasma perhexiline concentrations, 0.73 (0.21-1.00) vs. 0.36 (0.04-0.69) mg l(-1) (P = 0.04), lower cis-OH-perhexiline/perhexiline ratios, 2.85 (0.35-6.10) vs. 6.51 (1.84-11.67) (P = 0.03), and lower dextrorphan/dextromethorphan metabolic ratios, 2.51 (0.33-39.56) vs. 11.80 (2.90-36.93) (P = 0.005). CONCLUSIONS: Perhexiline significantly inhibits CYP2D6-catalysed metabolism in angina patients. The plasma cis-OH-perhexiline/perhexiline ratio may help to both phenotype patients and predict those in whom perhexiline may be most likely to cause clinically significant metabolic inhibition.

Aged↗
PubMed2004

Consensus guidelines on anti-cardiolipin antibody testing and reporting.

UNLABELLED: Consensus guidelines on anti-cardiolipin antibody (aCL) testing have been developed to help minimise laboratory variation in the performance and reporting of aCL assays. These guidelines include minimum, optimum and optional recommendations for the following aspects of aCL testing and reporting: (1) isotype of aCL tested; (2) specimen type; (3) controls and assay precision; (4) calibrators; (5) patient samples; (6) rheumatoid factors and IgM aCL testing; (7) reporting of results; (8) cut-off values; and (9) interpretative comments. ABBREVIATIONS: aCL, anti-cardiolipin antibodies; APS, anti-phospholipid antibody syndrome; ASCIA, Australasian Society of Clinical Immunology and Allergy; ASTH, Australasian Society of Thrombosis and Haemostasis; beta2-GPI=beta2-glycoprotein I; ELISA, enzyme-linked immunosorbent assay; NCCLS, National Committee for Clinical Laboratory Standards; HSANZ, Haematology Society of Australia and New Zealand; QAP, Quality Assurance Program; RCPA, Royal College of Pathologists of Australasia; %CV, inter-assay inter-run coefficient of variation.

Antibodies, Anticardiolipin↗
PubMed2004

A multi-centre evaluation of the intra-assay and inter-assay variation of commercial and in-house anti-cardiolipin antibody assays.

AIMS: To assess the intra-assay (intra-run) and inter-assay (inter-run) variation of commercial and in-house IgG and IgM anti-cardiolipin antibody (aCL) assays/kits, and to determine an appropriate maximum value for inclusion in consensus guidelines. METHODS: Frozen aliquots of two patient specimens and one commercial control were sent to nine laboratories for the evaluation of eight commercial kits and one in-house assay. Intra-assay and inter-assay evaluations were performed with all three samples for IgG aCL, and one patient specimen for IgM aCL. RESULTS: The IgG and IgM aCL values varied considerably between the nine assays/kits. The majority of assays/kits demonstrated less than 20% intra-assay and inter-assay variation, with lower intra-assay and inter-assay variation observed with the commercial control. Single calibrator assays were not consistently associated with higher inter-assay variation than multi-point calibrator assays. CONCLUSIONS: An inter-assay coefficient of variation of 20% was determined to be an appropriate maximum value for inclusion in the Australasian aCL Working Party consensus guidelines. Improved standardisation between different assay/kits is still required.

Antibodies, Anticardiolipin↗
PubMed2004

Anti-cardiolipin antibody testing and reporting practices among laboratories participating in a large external Quality Assurance Program.

AIMS: To investigate differences in anti-cardiolipin antibody (aCL) testing and reporting practices among diagnostic laboratories participating in the RCPA Quality Assurance Program (QAP) Immunology Program. METHODS: A survey was sent to all 58 laboratories enrolled for aCL testing in the RCPA QAP Program requesting the following information: (1). manufacturer/type of assay; (2). isotype tested; (3). use of calibrators and controls; (4). whether calibrators, control and patient specimens were performed in singles or duplicates; (5). whether results were reported semi-quantitatively and/or numerically; (6). values used to define negative/positive and semi-quantitative cut-offs and how they were determined; and (7). whether interpretative comments were provided and their content. RESULTS: Thirty-two surveys (55%) were received. Significant differences were present particularly in the following areas: (1). whether IgM isotype aCL testing was performed routinely or only on specific request; (2). whether controls/calibrators/specimens were tested in singles or duplicates; (3). whether results were reported numerically and/or semi-quantitatively; (4). the values used to define negative/positive and semi-quantitative range cut-offs; and (5). whether interpretative comments were provided and their content. CONCLUSIONS: These differences in testing and reporting practices are likely to contribute to the variation in aCL results reported by different laboratories, particularly among those using the same assay.

Antibodies, Anticardiolipin↗
PubMed2004

Role of local immunoglobulin E production in the pathophysiology of noninvasive fungal sinusitis.

OBJECTIVES/HYPOTHESIS: Immunoglobulin (Ig)E-mediated hypersensitivity to fungi has been postulated to explain allergic fungal sinusitis (AFS). Not all patients suspected to have AFS demonstrate systemic evidence of allergy. Locally produced IgE might explain those patients with no systemic evidence of allergy but clinical features of AFS. The aim was to determine whether fungal-specific IgE could be demonstrated in sinus mucin in patients with eosinophilic mucin rhino-sinusitis. STUDY DESIGN: A prospective study was undertaken in a tertiary rhinology practice in Adelaide, South Australia. METHODS: : Eighty-six consecutive patients with nasal polyposis and thick, colored macroscopically "fungal-like" sinus mucin at time of surgery for chronic sinusitis were entered in the study. The sinus mucin was liquefied and underwent testing for fungal-specific IgE (Pharmacia UniCAP) and fungal culture. Serum fungal-specific and total IgE, eosinophil count, C-reactive protein (CRP), and eosinophilic cationic protein (ECP) were measured. RESULTS: Fifty-six (65%) patients were fungal culture positive, and 37% had a detectable fungal-specific IgE in sinus mucin. Data were available to classify 81 patients: AFS = 24 (30%), AFS-like = 6 (7%), nonallergic eosinophilic fungal sinusitis = 32 (40%), nonallergic, nonfungal eosinophilic sinusitis = 19 (23%). Patients with AFS were significantly more likely to have fungal-specific IgE in sinus mucin (17/24, 71%, P =.02). In all fungal culture-positive patients, positive mucin fungal-specific IgE was significantly associated with systemic fungal allergy (P =.005), but a raised total serum IgE was not. Six (19%) of the 32 patients with positive fungal cultures but negative serum fungal-specific IgE had a positive mucin fungal-specific IgE, suggesting that they may be reclassified as AFS. The mean ECP and total IgE were raised most significantly in the AFS subgroup. CONCLUSIONS: This is the first study to show that fungal-specific IgE may be demonstrated in sinus mucin. It was significantly associated with systemic fungal allergy and may play a role in a minority of fungal sinusitis patients in the absence of systemic fungal allergy.

Adult↗
PubMed2004

A form of Jansen's metaphyseal chondrodysplasia with limited metabolic and skeletal abnormalities is caused by a novel activating parathyroid hormone (PTH)/PTH-related peptide receptor mutation.

A novel heterozygous PTH/PTHrP receptor missense mutation (T410R) was identified in a male and his two sons who are all affected by a less severe form of Jansen's metaphyseal chondrodysplasia (JMC). JMC is a rare disorder that is typically characterized by severe growth plate abnormalities that lead to short-limbed dwarfism. Furthermore, affected individuals usually show significant hypercalcemia, despite normal or undetectable levels of PTH and PTHrP. In contrast, the three affected members of this new family showed only mild skeletal dysplasia, comparatively normal stature, and blood calcium concentrations either within or at the upper end of the normal range. However, PTH levels were suppressed, and urinary calcium excretion was elevated, which led to nephrolithiasis in both children. When expressed in COS-7 cells, the PTH/PTHrP receptor with the T410R mutation led to agonist-independent cAMP formation, which was less pronounced than that observed with the previously identified T410P mutant. Our findings indicate that a mild form of JMC has been identified that is characterized by less pronounced skeletal and laboratory abnormalities.

Adult↗
PubMed2003

T cells and autoantibodies to human HSP70 in type 1 diabetes in children.

We studied T-cell proliferative responses (stimulation index: SI) and autoantibodies to human HSP60, HSP70 and HSP90 proteins in 25 children (mean age 10.1+/-3.8 years) newly diagnosed with Type 1 diabetes. The control group for T cells included 25 adults and three pediatric donors without Type 1 diabetes. Controls for antibodies included 10 pediatric subjects. The T-cell responses to HSP70 of the test group (mean SI=4.5+/-3.1) were significantly greater than those of the control group (meanSI=1.4+/-0.6; p<0.0001); the incidence of HSP70 responders was (85%) compared to 14% in the control group. All but three of the Type 1 children who responded to HSP70 also responded to HSP60 (85%). The T-cell responses of the Type 1 group to HSP90 (mean SI=1.7+/-1.1) were similar to those of the control group (mean SI=1.5+/-0.7). We mapped HSP70 epitopes recognized by T cells in seven subjects using overlapping peptides of the molecule. Among the Type 1 subjects, IgG seropositivity was 45% to HSP60, 30% to HSP70, and 15% to HSP90. Thus, we conclude that children with newly diagnosed Type 1 diabetes manifest heightened T-cell autoimmunity to HSP70 and HSP60, but not to HSP90.

Adolescent↗
PubMed2002

Adult infection with hepatitis A despite declining endemicity; in favor of adult vaccination.

Seropositivity against hepatitis A was examined among 4806 standing army personnel (4497 males and 309 females) during 1998-1999. Each bi-annual birth cohort examined showed a decline in seropositivity compared to the previous one. When compared with a study performed in 1989, however, for each of the 1961-1962, 1963-1964, 1965-1966, 1967-1968 and 1969-1970 birth cohorts examined, the 1998-1999 study showed 5-15% higher seropositivity. This trend remained after controlling for differences between the two studies in ethnic origin, sibship size and level of education. The overall seroconversion rate is estimated as 1.15% per year and the clinical to subclinical ratio as 1:14. Thus, hepatitis A infection continues to occur in the young adult age group and vaccination of this group should be considered.

Adult↗
PubMed2002

An autopsy approach to bee sting-related deaths.

Although severe reactions to the sting of the common honey bee (Apis mellifera) are a common problem in Australia, reported deaths are uncommon, with the estimated mortality varying from one to four persons each year. The following study presents the postmortem findings in three cases of bee sting fatality, including one in which no observable sting was found. An autopsy approach to such cases is detailed. Overreporting of bee sting-related deaths may occur due to the inclusion of deaths unrelated to a reaction to bee venom, while under-reporting may be due to unexplained deaths where a history of a bee sting is not available or apparent at autopsy. A classification of bee sting-related deaths is proposed, which would allow more accurate reporting of bee sting-related fatalies. A serum tryptase and specific IgE to bee venom on serum obtained at autopsy can assist in confirming anaphylactic reaction to bee venom as the cause of death, particularly in the absence of observable stings. Although there are limitations to the usefulness of serum tryptase tests in the postmortem situation, it may still be useful to confirm suspected anaphylaxis in autopsy cases with an undetermined cause of death.

Adult↗