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Biomedical subjects

A Chalmers

Publications and source records attributed to A Chalmers.

At least 19 recordsLinked to original sources
PubMed2003

Symptoms of asthma: comparison of a parent-completed retrospective questionnaire with a prospective daily symptom diary.

In a study of the effects of indoor air pollution on the respiratory health of children in Newcastle, Australia, parental reports of symptoms experienced by children over the previous 12 months were compared with a prospective record of symptoms of cough and wheeze. Parents of 390 children aged 8-11 years completed a questionnaire about child and family respiratory health, which was used to assign children to one of four symptom groups: Wheeze (two or more attacks of wheezing in the last 12 months), Chest-Colds (two or more chest-colds in the last 12 months without wheezing), Cough Alone (a dry cough at night, without a cold or chest infection, that lasted for more than 2 weeks), or Control (none). A balanced sample of children (n=139) was invited to participate further by completing lung function tests, atopy testing, and keeping a daily diary of peak expiratory flow (PEF) and symptoms of cough and wheeze over a 7-week period. Valid data for the daily diary were provided by 66/85 (77.6%) of participants who commenced this stage (47.5% of the 139 invited to participate). The Wheeze group reported significantly more subsequent wheeze (median 16.8% of days) than the other three groups (median 0% of days). Parent reports of asthma-like symptoms over the previous 12 months were consistent with the subsequent experience of symptoms recorded in a daily diary.

Adult↗
PubMed2002

The increasing role of percutaneous transluminal angioplasty in the primary management of critical limb ischaemia.

OBJECTIVE: to review the current role and results of angioplasty in the management of critical limb ischaemia (CLI) in a single institution. METHODS: data on 526 patients with 608 ischaemic limbs, treated between January 1994 and December 1999 was collected prospectively and analysed retrospectively. Patients were divided into 3 groups according to the date of presentation: group 1 (1994-95), group 2 (1996-97) and group 3 (1998-99). The groups were comparable in terms of demographics, mode of presentation and level of disease. RESULTS: Revascularisation was attempted in 87%, 81% and 91% for groups 1, 2 and 3 respectively (NS). Primary percutaneous transluminal angioplasty (PTA) rates increased from 44% (1994-95) to 69% (1998-99) (p < 0.001), and surgical revascularisation rates decreased correspondingly (p<0.01). Overall cumulative patient survival and limb salvage rates were 82% and 89% for 1 year and 45% and 87% for 5 years, respectively. No statistically significant difference existed between the three groups regarding patient survival, limb salvage rates and mean hospital stay (19, 12 and 12 days, respectively). CONCLUSION: PTA is increasingly replacing bypass surgery in the treatment of CLI, without compromising patient survival or limb salvage rates.

Aged↗
PubMed2001

The effectiveness and toxicity of cyclosporin A in rheumatoid arthritis: longitudinal analysis of a population-based registry.

OBJECTIVE: To determine factors associated with response or toxicity to cyclosporin A (CSA) in a population-based inception cohort with rheumatoid arthritis (RA). METHODS: Prospectively collected longitudinal measures including tender joint count (JC), duration of morning stiffness (MS), systolic and diastolic blood pressure (SBP, DBP), and serum creatinine (SCr) were modeled using generalized estimating equations. Survival methods were used to estimate CSA continuation time and its determinants. RESULTS: Of 133 patients (75% female, median RA duration 13 years), 37 discontinued CSA because of ineffectiveness (19) or because of toxicity (18) including increased SCr in 10, hypertension in 4, infections in 3, and gingival hyperplasia in 1. Patients remained on CSA a median of 75 months (95% confidence interval [CI] 38-112). Those receiving concomitant methotrexate (MTX) were more than 4 times as likely to continue on CSA therapy (hazard ratio 0.22, 95% CI 0.10-0.94). A lower final JC was predicted by a longer CSA treatment duration (relative risk [RR] 0.99 per month, 95% CI 0.98-0.99) and concomitant MTX therapy (RR 0.79, 95% CI 0.63-0.99); decreased MS was predicted only by longer CSA treatment duration (reduction of 2.0 minutes per month, 95% CI 1.1-3.0). Each previous disease-modifying antirheumatic drug (DMARD) exposure predicted a rise in SCr (35 micromole/liter, 95% CI 22-48), SBP (7.2 mm Hg, 95% CI 2.7-11.7), and DBP (3.8 mm Hg, 95% CI 3.0-6.4). CONCLUSIONS: Combination CSA/MTX prolongs therapy and reduces JC. Long-term CSA treatment was fairly well tolerated. Previous DMARD use appears to be a determinant for the development of toxicity.

Adult↗
PubMed2001

Identification of four novel dinucleotide repeat polymorphisms in the IL-2 and IL-2beta receptor genes.

Two polymorphic regions have been described within the IL-2 and IL-2 receptor beta genes comprising 15 and 8 alleles, respectively. Whether these polymorphisms have biologic importance is unknown, although they have been variably identified in associated with certain chronic disease states. We report here the detection of four new alleles designated IL-2 A* (122 bp), IL-2R-2 (169 bp), IL-2R 0 (165 bp), and IL-2R 9 (147 bp) in patients with rheumatoid arthritis and normal controls from the Pacific Northwest. The number of alleles now recognized at these loci within the IL-2 and IL-2Rbeta genes increases to 16 and 12, respectively.

Alleles↗
PubMed2001

Crk family adaptor proteins trans-activate c-Abl kinase.

BACKGROUND: c-Abl kinase is activated in response to a variety of biological stimuli. Crk family adaptor proteins can interact physically with c-Abl and be involved in the activation of c-Abl kinase. RESULTS: We report that the Crk family of adaptor proteins act as trans-acting activators of c-Abl kinase. The interaction of the amino-terminal Src-homology (SH) 3 domain of c-Crk and the proline-rich motifs of c-Abl is an essential step for the phosphorylation of c-Crk by c-Abl, as well as the activation of c-Abl by c-Crk. The activation of c-Abl by c-Crk is negatively regulated by phosphorylation of the tyrosine 221 of c-Crk. Our data suggest that, in the absence of phosphorylation of the tyrosine Y221, the SH2 domain of c-Crk becomes free to bind to target molecules while the carboxyl-terminal SH3 domain of c-Crk binds to the proline-rich region of c-Abl, inducing the activation of c-Abl by c-Crk. CONCLUSION: This study suggests that the Crk family functions as trans-acting activators of c-Abl kinase. The phosphorylation of c-Crk may regulate c-Abl kinase.

Animals↗
PubMed2001

The effects of levels of immersion on memory and presence in virtual environments: a reality centered approach.

Simulation fidelity is characterized as the extent to which a Virtual Environment (VE) and relevant interactions with it are indistinguishable from a user's interaction with a real environment. The growing number of VE training applications which target a high level of simulation fidelity, mainly for transfer of training in the real world, have made it crucial to examine the manner in which these particular implementations and designs are evaluated. The methodology presented in this study focuses on real versus simulated virtual worlds, comparing participants' level of presence, task performance, and cognition state employed to complete a memory task. A 15-minute seminar was presented in four different conditions including real, 3D desktop, 3D Head Mounted Display (HMD) and Audio-only (between-subjects design). Four independent groups of 18 participants took part in the experiment, which investigated the effects of levels of immersion on participants' memory recall and memory awareness state (relevant to episodic and semantic memory types) as well as on their perception of the experimental space and sense of presence for every condition. The level of reported presence was not positively associated with accurate memory recall in all conditions, although the scores for both presence and seminar memory recall in the "real" condition were statistically higher. Memory awareness states' analysis gave a invaluable insight into "how" participants remembered both communicated information and space, as opposed to "what," most interestingly across specific conditions where results for presence and accurate memory recall were not proven to be significant.

Adult↗
PubMed2000

Association between dinucleotide repeat in non-coding region of interferon-gamma gene and susceptibility to, and severity of, rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis ranges from a mild, non-deforming arthropathy with little long-term disability to severe, incapacitating, deforming arthritis which may be refractory to conventional disease-modifying agents. Epidemiological studies show an important genetic influence in rheumatoid arthritis, and MHC region genes and cytokine genes within and outside this region have been considered as candidates. We did a case-control study to test whether polymorphisms in the interferon-gamma gene are associated with severity of rheumatoid arthritis. METHODS: Interferon gamma dinucleotide repeat polymorphisms were examined with quantitative genescan technology, and HLA-DR alleles were identified by PCR and restriction-fragment-length polymorphism analysis. We studied 60 patients with severe rheumatoid arthritis, 39 with mild disease, and 65 normal controls. FINDINGS: Susceptibility to, and severity of, rheumatoid arthritis were related to a microsatellite polymorphism within the first intron of the interferon-gamma gene. A 126 bp allele was seen in 44 (73%) of 60 patients with severe rheumatoid arthritis, compared with eight (21%) of 39 with mild disease (odds ratio 10.66 [95% CI 4.1-24.9]), and with eight (12%) of 65 normal controls (19.59 [7.7-49.9]). Conversely, a 122 bp allele at the same locus was found in four (7%) patients with severe disease compared with 25 (64%) of those with mild disease (0.04 [0.01-0.1]) and with 52 (80%) of controls (0.018 [0.005-0.06]). INTERPRETATION: This association may be valuable for understanding the mechanism of disease progression, for predicting the course of the disease, and for guiding therapy.

Adult↗
PubMed2000

Cyclosporin A in the treatment of refractory adult polymyositis/dermatomyositis: population based experience in 6 patients and literature review.

OBJECTIVE: To evaluate the efficacy and toxicity of cyclosporin A (CSA) in the treatment of refractory adult polymyositis/dermatomyositis (PM/DM). METHODS: The province-wide British Columbia database for CSA use for persons with rheumatic diseases at Mary Pack Arthritis Centre was reviewed to identify all patients with PM/DM for the period January 1991 through June 1998. Also, a Medline search of English language literature was conducted for this topic from 1976 until January 1999, using the terms dermatomyositis, polymyositis, inflammatory myopathy, and cyclosporin A, and the reference lists of all papers were screened to include articles not identified by the Medline search. RESULTS: In British Columbia, 172 CSA users of whom 6 had PM/DM were identified (4 PM, 2 DM). Previous therapy included high dose prednisone (N = 6), methotrexate (N = 4), azathioprine (N = 4), intravenous immunoglobulin (N = 3), and cyclophosphamide (N = 3). The mean CSA dose was 3.5 mg/kg/day. All patients improved. Creatinine kinase (CK) levels declined 52% from baseline. All 6 patients continued CSA a median of 6 months (range 3-44 mo) after initiation of therapy. Toxicity included an increase in serum creatinine > 30% of baseline in 3 patients and hypertension in one patient. The literature review identified an additional 59 cases. Forty-eight (81%) had a reduction in CK levels and improved clinically, 9/59 (15%) developed nephrotoxicity, 5/59 (8%) hypertension responsive to dose reduction, and 9/59 (15%) had hypertrichosis, gingival hyperplasia, or tremor. CONCLUSION: Our population based experience with 6 patients and the 59 published cases suggests CSA is an effective therapy for resistant PM/DM, and toxicity is possibly more than expected in other rheumatic diseases.

Adult↗
PubMed1999

Conversion of patients with rheumatoid arthritis from the conventional to a microemulsion formulation of cyclosporine: a double blind comparison to screen for differences in safety, efficacy, and pharmacokinetics.

OBJECTIVE: To assess whether patients with rheumatoid arthritis (RA) may be converted, on a milligram-to-milligram basis, from conventional cyclosporin A (CyA, Sandimmun) to the microemulsion formulation (Neoral) with maintenance of longterm safety, and to compare cyclosporin A (CyA) pharmacokinetics between formulations. METHODS: In this double blind, multicenter, parallel group study, 51 patients receiving stable conventional CyA maintenance treatment were randomized to continue conventional CyA (n = 27) or to convert to CyA microemulsion (n = 24) and were monitored for 52 weeks. Trough blood CyA levels were measured before and at intervals after conversion. CyA steady-state area under the curve was assessed one week before and 2 and 6 weeks after randomization in 15 patients in each treatment arm. CyA trough levels and pharmacokinetic results remained unknown to investigators throughout the study. CyA doses were titrated as necessary on the basis of clinical evaluation and disease activity assessments. RESULTS: Initial mean daily doses were 3.5 mg/kg/day (conventional CyA) and 3.3 mg/kg/day (CyA microemulsion) and did not change significantly during the study. The mean bioavailability of CyA from the microemulsion formulation was 23% higher than from conventional CyA. Replicate assessments indicated a more reproducible pharmacokinetic profile with CyA microemulsion. The overall incidence and nature of adverse events and changes in vital signs and laboratory variables were similar in both groups. No clinically relevant differences in efficacy were found between treatments. No loss of efficacy and no tolerability problems occurred after conversion from conventional to microemulsion CyA. CONCLUSION: Existing CyA dosing guidelines, formulated for conventional CyA, are suitable for longterm CyA microemulsion therapy of patients with RA. These results indicate the pharmacokinetic advantages of the microemulsion formulation.

Antirheumatic Agents↗
PubMed1998

A comparison of multimedia and standard advanced cardiac life support learning.

OBJECTIVES: To compare student performance after Multimedia ACLS Learning System (MM) education compared with that after standard (ST) ACLS education. METHODS: Final-year medical students were divided into 2 groups based on convenience scheduling and given ACLS instruction either in a standard format or with the MM course. The sizes of the small groups and the times in small-group instruction were identical. All students were evaluated with the same 50-item multiple-choice written examination, a structured evaluation immediately after the management of a mock cardiac arrest, and a second structured evaluation of the same mock arrest (videotaped) by an instructor blinded to the education method. Students were assigned a mark from 1 to 5 in each of 4 domains: assessment, immediate priorities, continual assessment, and leadership. RESULTS: 75 students took the MM and 38 took the ST course. The mean +/- SD mark for the multiple-choice test was 89.3 +/- 4.9% (MM) vs 89.3 +/- 4.8% (ST); the on-site mock arrest evaluation mark (20 maximum) was 14.1 +/- 2.5 (MM) vs 14.1 +/- 2.0 (ST); and the blinded mock arrest evaluation was 13.1 +/- 2.9 (MM) vs 14.4 +/- 2.9 (ST) (p = 0.024). 1/75 (MM) vs 0/38 (ST) did not successfully complete the on-site mock arrest evaluation. More students in the MM group (46% vs 25%) required multiple attempts to successfully complete the mock arrest evaluation (p < 0.02). CONCLUSION: In medical students with no previous ACLS training, structured access to the multimedia ACLS Learning System provides immediate educational outcomes similar to those of a standard ACLS course. Multimedia computer-interactive learning should be enhanced with a short period of hands-on practice.

British Columbia↗
PubMed1997

Randomised double-blind placebo-controlled study on adverse effects of rubella immunisation in seronegative women.

BACKGROUND: The objective of our study was to investigate the association of adverse clinical musculoskeletal and neurological events in healthy postpartum women with live attenuated (RA27/3 strain) rubella-virus vaccine, and to assess the frequency of acute and recurrent arthralgia and arthritis and associations with acute and recurrent muscle pain (myalgia) and neurological manifestations (paraesthesias). METHODS: We used a randomised placebo-controlled, double-blind design in a community setting. 636 women were enrolled and, after 90 women dropped out, 546 healthy women aged 18-41 years, who were rubella seronegative on routine screening were immunised parenterally with either monovalent live attenuated (RA27/3 strain) rubella vaccine (n = 270) or saline placebo (n = 276) in the postpartum period. Outcome measures were the occurrence of acute and persistent or recurrent joint manifestations (arthralgia or arthritis) at 1, 3, 6, 9, and 12 months after immunisation. Occurrence of muscle pain (myalgia), and neurological symptoms (paraesthesia) was also assessed at the same times. FINDINGS: 543 women completed 1-month follow-up. 456 women completed the 12-month assessment. There were no differences at the time of immunisation between rubella vaccine and placebo groups in distribution of age, ethnic origin, parity, time between delivery and immunisation, breastfeeding history, or histories of earlier rubella vaccination or joint complaints. Results indicated a significantly higher incidence (p = 0.006; odds ratio = 1.73 [95% CI = 1.17-2.57]) of acute joint manifestations in rubella-vaccine recipients (30%) than in placebo recipients (20%). Frequency of chronic (recurrent) arthralgia or arthritis was only marginally significant (p = 0.042; 1.58 [1.01-2.45]). INTERPRETATION: RA27/3 rubella vaccine given to seronegative women during the postpartum period was significantly associated with development of acute arthralgia or arthritis. Although the numbers of women assessed and length of follow-up revealed only marginally significant differences in persistent or recurrent joint manifestations between rubella vaccine and placebo recipients, it is possible that susceptible women who are given rubella vaccination may experience this outcome.

Adolescent↗
PubMed1997

Advances in mucosal immunology.

HIV infection is likely to remain a significant medical and scientific problem well into the twenty-first century. During the first 15 years of the epidemic, much has been learned about the biology of HIV infection, but the majority of biomedical research has focused on the peripheral circulation. It is likely that the behavior of the virus within the unique immunologic environment of the intestinal mucosa differs from that which is observed in the periphery. Many clinical and epidemiologic features of HIV infection offer compelling reasons to encourage further examination of the mucosal immune system's role in AIDS pathogenesis. This article has touched on most of the significant observations concerning the mucosal immune system and HIV infection, and it is clear that much remains to be done. As mentioned earlier, the mucosal abnormalities observed in HIV infection are likely to have many causes. Careful evaluation of patients with early disease and fewer confounding variables may provide fresh insight into AIDS pathogenesis. Similarly, prospective evaluation of selected patient populations may be more informative in characterizing the progressive alterations in mucosal immune function than random cross-sectional studies of poorly defined groups. It is equally important for immunologic assessment to be correlated with nutritional and symptomatic evaluation. Finally, the success or failure of future antiretroviral therapies will be critically related to the impact of such agents on lymphoid reservoirs of HIV infection such as the gastrointestinal tract, which are at present refractory to treatment.

Antigen-Presenting Cells↗
PubMed1997

Microscopic polyangiitis after influenza vaccination.

We describe a case of microscopic polyangiitis involving skin and joints after influenza vaccination. Titers of antiinfluenza A antibody were markedly elevated in synovial fluid (SF) relative to those in serum. Antiinfluenza B antibodies were not present in SF but were present in serum, suggesting a reaction specifically involving antiinfluenza A antibodies localized to the affected joint. A review identified 16 other cases of vasculitis after influenza vaccination. The cases reclassified according to the Chapel Hill diagnostic criteria identified multiple forms of vasculitis including 7 other cases of microscopic polyangiitis. Three patients had similar illnesses after previous influenza vaccination or influenza-like illness. As in our case 11 cases resolved without recurrence. While this does not provide conclusive evidence that the vaccination caused the vasculitis, together with the serologic data we present it supports this hypothesis.

Adult↗
PubMed1995

Acute local reactions after intraarticular hylan for osteoarthritis of the knee.

OBJECTIVE: To describe acute local reactions following intraarticular hylan injection and determine their frequency. METHODS: Retrospective review of all patients with osteoarthritis of the knee treated with hylan by 3 rheumatologists. RESULTS: Twenty-two patients had 88 injections to 28 knees. Six patients had reactions within 24 h of injection characterized by pain, warmth, and swelling, lasting up to 3 weeks. This occurrence was unpredictable. Corticosteroid injections were sometimes required. Synovial fluid cell counts were 5.0-75.0 x 10(9)/l, often with a prominent mononuclear component. Crystal studies and cultures were negative. Radiographic chondrocalcinosis was present in only 1 patient. One patient had serum antibodies to chicken serum proteins. CONCLUSION: Intraarticular hylan was associated with significant local inflammatory reactions in 27% of patients, or 11% of injections. The mechanism(s) and long term sequelae are unclear.

Adult↗
PubMed1995

Cyclosporin A in the treatment of adult Still's disease.

Cyclosporin A (CyA) has been used successfully in the treatment of rheumatoid arthritis. There is one case report of CyA used successfully in the treatment of severe systemic onset Still's disease. To our knowledge, there are no reports of CyA used in adult Still's disease. We present the first report of a patient with refractory adult Still's disease successfully treated with CyA. We submit that cyclosporine treatment may induce remission of symptoms in patients with adult Still's disease and reduce the steroid requirements.

Adult↗