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Biomedical subjects

M Judd

Publications and source records attributed to M Judd.

At least 19 recordsLinked to original sources

Tai chi for treating rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disease that results in the destruction of the musculoskeletal system. The major goals of treatment are to relieve pain, reduce inflammation, slow down or stop joint damage, prevent disability, and preserve or improve the person's sense of well-being and ability to function. Tai Chi, interchangeably known as Tai Chi Chuan, is an ancient Chinese health-promoting martial art form that has been recognized in China as an effective arthritis therapy for centuries. OBJECTIVES: To assess the effectiveness and safety of Tai Chi as a treatment for people with RA. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (CCTR), MEDLINE, Pedro and CINAHL databases up to September 2002, using the Cochrane Collaboration search strategy for randomised controlled trials. We also searched the Chinese Biomedical Database up to December 2003 and the Beijing Chinese Academy of Traditional Medicine up to December 2003. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials examining the benefits and harms of exercise programs with Tai Chi instruction or incorporating principles of Tai Chi philosophy were selected. We included control groups who received no therapy, sham therapy or another type of therapy. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included in this review, rated the methodological quality and extracted data using standardized forms. MAIN RESULTS: Four trials including 206 participants, were included in this review. Tai Chi-based exercise programs had no clinically important or statistically significant effect on most outcomes of disease activity, which included activities of daily living, tender and swollen joints and patient global overall rating. For range of motion, Tai Chi participants had statistically significant and clinically important improvements in ankle plantar flexion. No detrimental effects were found. One study found that compared to people who participated in traditional ROM exercise/rest programs those in a Tai Chi dance program reported a significantly higher level of participation in and enjoyment of exercise both immediately and four months after completion of the Tai Chi program. REVIEWERS' CONCLUSIONS: The results suggest Tai Chi does not exacerbate symptoms of rheumatoid arthritis. In addition, Tai Chi has statistically significant benefits on lower extremity range of motion, in particular ankle range of motion, for people with RA. The included studies did not assess the effects on patient-reported pain.

Arthritis, Rheumatoid↗

Thermotherapy for treatment of osteoarthritis.

BACKGROUND: Osteoarthritis is a degenerative joint disease that affects mostly the weight-bearing joints in the knees and hips. As the affected joint degenerates pain and restriction of movement often occur. Inflammation can also occur sometimes resulting in edema of the joint with OA. Treatment focuses on decreasing pain and improving movement. OBJECTIVES: To determine the effectiveness of thermotherapy in the treatment of OA of the knee. The outcomes of interest were relief of pain, reduction of edema, and improvement of flexion or range of motion (ROM) and function. SEARCH STRATEGY: Two independent reviewers selected randomized and controlled clinical trials with participants with clinical and/or radiological confirmation of OA of the knee; and interventions using heat or cold therapy compared with standard treatment and/or placebo. Trials comparing head to head therapies, such as two different types of diathermy, were excluded. SELECTION CRITERIA: Randomized and controlled clinical trials including participants with clinical or radiographical confirmation of OA of the knee; and interventions using heat or cold compared to standard treatment or placebo were considered for inclusion. DATA COLLECTION AND ANALYSIS: Study results were extracted by two independent reviewers. Outcomes were continuous in nature (pain, strength, improvement) and were analyzed by weighted mean difference using a fixed effects model. Graphical data were used when table data were not available. MAIN RESULTS: Three randomized controlled trials, involving 179 patients, were included in this review. The included trials varied in terms of design, outcomes measured, cryotherapy or thermotherapy treatments and overall methodological quality. In one trial, administration of 20 minutes of ice massage, 5 days per week, for 3 weeks, compared to control demonstrated a clinically important benefit for knee OA on increasing quadriceps strength (29% relative difference). There was also a statistically significant improvement, but no clinical benefit in improving knee flexion ROM (8% relative difference) and functional status (11% relative difference). Another trial showed that cold packs decreased knee edema. REVIEWER'S CONCLUSIONS: Ice massage compared to control had a statistically beneficial effect on ROM, function and knee strength. Cold packs decreased swelling. Hot packs had no beneficial effect on edema compared with placebo or cold application. Ice packs did not effect pain significantly compared to control in patients with OA. More well designed studies with a standardized protocol and adequate number of subjects are needed to evaluate the effect of thermotherapy in the treatment of OA of the knee.

Cryotherapy↗

Etanercept for the treatment of rheumatoid arthritis.

BACKGROUND: Etanercept is a soluble tumour necrosis factor alpha-receptor DMARD for the treatment of rheumatoid arthritis (RA). OBJECTIVES: To assess the efficacy and safety of etanercept for the treatment of RA. SEARCH STRATEGY: Five electronic databases were searched from 1966 to February 2003 with no language restriction. SELECTION CRITERIA: All randomized controlled trials (minimum 6 month duration) comparing three possible combinations 1) etanercept (10 mg or 25 mg twice weekly) with methotrexate (MTX) to MTX alone 2) etanercept to MTX, or 3) etanercept to placebo were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed the methodological quality of the trails. The American College of Rheumatology (ACR) core set of disease activity measures for RA clinical trials, radiographic, withdrawals and toxicity outcomes were analyzed. MAIN RESULTS: Three trials were included in this review. Two trials compared an experimental group who were started on etanercept compared to a control group; both groups had the same ongoing background therapy of nonsteroidals in both trials plus in one trial one group was on stable methotrexate. In these two trials the ACR 20, ACR 50 and ACR 70 response rates at 6 months were statistically significantly and clinically important with etanercept 25 mg subcutaneous injections (SC) twice weekly. Sixty-four percent of people receiving etanercept ache vied an ACR 20 response compared to 15% of controls and the number needed to treat (NNT) with etanercept is 2 people. Thirty-nine percent of those receiving etanercept achieved an ACR 50 response compared to 4% of taking control treatment and the NNT is three. Fifteen percent of people taking etanercept achieved an ACR 70 compared to 1% of controls with a NNT of 7 people. In the third trial of starting etanercept compared to starting methotrexate the number of participants who achieved an ACR 20, 50 or response at 6 and 12 months were not statistically significant for either etanercept dose. Etanercept treatment showed a statistically significantly and clinically important affect on joint damage as measured by the Sharp erosion score. Among participants who received etanercept 72% had no increase in their erosion score compared to 60% of participants in the methotrexate group. Withdrawal and toxicity results were acceptable. REVIEWER'S CONCLUSIONS: Etanercept 25 mg SC twice weekly was more efficacious than control treatment for ACR 20, 50 and 70 at 6 months, and over 12 months it slowed joint damage.

Antirheumatic Agents↗

Electromagnetic fields for the treatment of osteoarthritis.

BACKGROUND: As the focus for osteoarthritis (OA) treatment shifts away from drug therapy, we consider the effectiveness of pulsed electric stimulation which is proven to stimulate cartilage growth on the cellular level. OBJECTIVES: 1)To assess the effectiveness of pulsed electric stimulation for the treatment of osteoarthritis (OA). 2) To assess the most effective and efficient method of applying an electromagnetic field, through pulsed electromagnetic fields (PEMF) or electric stimulation, as well as the consideration of length of treatment, dosage, and the frequency of the applications. SEARCH STRATEGY: We searched PREMEDLINE, MEDLINE, HealthSTAR, CINAHL, PEDro, and the Cochrane Controlled Trials Register (CCTR) up to and including 2001. This included searches through the coordinating offices of the trials registries of the Cochrane Field of Physical and Related Therapies and the Cochrane Musculoskeletal Group for further published and unpublished articles. The electronic search was complemented by hand searches and experts in the area. SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials that compared PEMF or direct electric stimulation against placebo in patients with OA. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included in the review based on inclusion and exclusion criteria (JH,VR) and extracted the data using pre-developed extraction forms for the Cochrane Musculoskeletal Group. The methodological quality of the trials was assessed by the same reviewers using a validated scale (Jadad 1996). Osteoarthritis outcome measures were extracted from the publications according to OMERACT guidelines (Bellamy 1997) and additional secondary outcomes considered. MAIN RESULTS: Only three studies with a total of 259 OA patients were included in the review. Electrical stimulation therapy had a small to moderate effect on outcomes for knee OA, all statistically significant with clinical benefit ranging from 13-23% greater with active treatment than with placebo. Only 2 outcomes for cervical OA were significantly different with PEMF treatment and no clinical benefit can be reported with changes of 12% or less. REVIEWER'S CONCLUSIONS: Current evidence suggests that electrical stimulation therapy may provide significant improvements for knee OA, but further studies are required to confirm whether the statistically significant results shown in these trials confer to important benefits.

Clinical Trials as Topic↗

Rofecoxib for the treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, in which the synovial lining of many joints and tendon sheaths are persistently inflamed. OBJECTIVES: To assess the efficacy and toxicity of rofecoxib for treating RA. SEARCH STRATEGY: We searched the following databases up to December 2000: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment database. The bibliographies of retrieved papers were scanned for additional references. The manufacturers of rofecoxib, MSD, were also approached by the UK National Institue for Clincal Excellence to submit additional evidence to inform it's appraisal on the use of cyclo-oxygenase inibitors for arthritis. SELECTION CRITERIA: Relevant studies were randomised controlled trials of parallel group design evaluating the efficacy and/or toxicity of rofecoxib in RA, both placebo based and comparative trials were eligible. Relevant outcome criteria had to be available to evaluate efficacy and/or toxicity, such as the OMERACT outcomes. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers and the results were compared for the degree of agreement. A validated tool (Jadad 1995) was used to score the quality of the randomised controlled trials. The planned analysis was to pool, where appropriate, continuous outcome measures using mean or standardized mean differences, and dichotomous outcome measures using relative risk ratios. MAIN RESULTS: Two randomised controlled trials evaluating the efficacy and toxicity of rofecoxib in RA were identified and met the criteria. One compared rofecoxib to placebo and the other compared rofecoxib to naproxen. The overall number of ACR 20 responders who had received 25mg (82/ 171 = 48%) or 50mg (86/161 = 53%) was statistically significantly more than those receiving placebo (58/168 = 35% ) (RR 1.39 CI: 1.07, 1.80 and RR 1.55 CI: 1.20, 1.99 respectively) with no statistically significant differences between the 25 and 50 mg doses. The safety profile of rofecoxib was similar to that of placebo. In the comparative trial, rofecoxib at a dosage of 50 mg/day demonstrated similar efficacy to naproxen at a dosage of 500 mg twice daily. However, the combined rate of clinically significant complicated gastro-intestinal events (GI) (perforations, ulcers, bleeds, or obstructions) was lower with rofecoxib than with naproxen (RR 0.46, 95% CI, 0.34 to 0.63) due to a reduction in the number of ulcers and bleeds. Patients taking rofecoxib had a greater risk of having a myocardial infarction (MI) than patients taking naproxen (RR 4.03, 95% CI, 2.86 to 5.68). REVIEWER'S CONCLUSIONS: In patients with RA, rofecoxib demonstrates a greater degree of efficacy than placebo, while having a comparable safety profile. Rofecoxib demonstrates a similar degree of efficacy as naproxen, but with a significantly lower rate of ulceration and gastrointestinal bleeding. Rofecoxib was associated with a greater risk for MI, but the exact significance and pathophysiology of this possible relationship is unclear.

Anti-Inflammatory Agents, Non-Steroidal↗

Infliximab for the treatment of rheumatoid arthritis.

BACKGROUND: Infliximab is a human murine chimeric anti-tumour necrosis factor alpha monoclonal antibody recently approved for the treatment of refractory RA. OBJECTIVES: To assess the efficacy and safety of infliximab for the treatment of rheumatoid arthritis. SEARCH STRATEGY: Electronic databases including Biological Abstracts, CINAHL, Current Contents, Dissertation Abstracts, EBM Reviews, HealthSTAR and MEDLINE were searched from 1966 to March 2002. Rheumatoid arthritis was searched as an exploded MESH heading. Infliximab was searched as a text word as it is not currently indexed. The search was not limited by language, year of publication or type of publication. The specific search strategy is shown below. SELECTION CRITERIA: All randomized controlled trials comparing infliximab 1, 3, 5 or 10 mg/kg with methotrexate(MTX) to MTX alone, or without MTX to placebo, with a minimum duration of 6 months and at least 2 infusions were eligible. DATA COLLECTION AND ANALYSIS: Data was extracted by 2 independent reviewers and the methodological quality of the trials was assessed using a validated assessment tool scale. Outcome variables included the ACR core set of disease activity measures for RA clinical trials and radiographic outcome data. Withdrawals and toxicity were also included. End of trial results were pooled. Continuous data were pooled using weighted mean differences and dichotomous data using relative risks. MAIN RESULTS: Two trials with a total of 529 patients met the inclusion criteria. Patients fulfilling the American Rheumatism Association 1987 RA diagnostic criteria were randomized to receive either infliximab 1mg/kg (with and without MTX), 3mg/kg(with and without MTX), 10mg/kg of infliximab (with and without MTX) or placebo infusion plus MTX. Infusions were given every 4 or 8 weeks. After 6 months ACR 20, ACR 50 and ACR 70 response rates were significantly improved in all infliximab doses compared to control. The number needed to treat with infliximab to achieve an ACR 20, 50 or 70 response in patients with refractory RA under specialist care ranged from 2.9 to 3.3 for ACR 20, 3.6 to 4.8 for ACR 50 and 5.9 to 12.5 for ACR 70 depending on the dose (3mg/kg or 10mg/kg given either every 4 or 8 weeks). Total withdrawals and withdrawals due to lack of efficacy were lower for all doses of infliximab versus controls. Withdrawals for adverse events and withdrawals for other reasons were not statistically significantly different for those receiving infliximab from control. REVIEWER'S CONCLUSIONS: Treatment with infliximab for 6 and 12 months significantly reduces RA disease activity and appeared to have an acceptable safety profile in these trials. Total radiographic scores improved, fewer patients showed radiographic progression, and more patients showed radiographic improvement with infliximab treatment at 12 months compared to controls. However, only 2 trials met the inclusion criteria, and these results are largely driven by the largest trial. The available efficacy and toxicity data is relatively short-term (6-12 months). In order to detect rare events that may be associated with infliximab, larger and longer term studies are required.

Antibodies, Monoclonal↗

Therapeutic ultrasound for the treatment of rheumatoid arthritis.

BACKGROUND: Ultrasound is often used, by rehabilitation specialists, as an adjunct therapy for the symptomatic treatment of rheumatoid arthritis (RA). Its mechanical energy has antiinflammatory as well as analgesic properties. OBJECTIVES: To evaluate the effects of ultrasound on objective and subjective measures of disease activity in patients with RA. SEARCH STRATEGY: A comprehensive search was conducted up to September 2001 with MEDLINE, EMBASE, PEDro, Current Contents, Sports Discus and CINAHL. The Cochrane Field of Rehabilitation and Related Therapies and the Cochrane Musculoskeletal Review Group specialized registers were also searched. Handsearching was conducted on all retrieved papers and content experts were contacted to identify additional studies. SELECTION CRITERIA: Comparative controlled studies, such as randomized controlled trials and clinical controlled trials in patients with RA were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all the extracted data. Quality was assessed by two reviewers using a 5 point validated assessment tool that measures the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Two studies (n=80 participants) met the inclusion criteria. Ultrasound to the palmar and dorsal aspect of the hand significantly increases grip strength when compared to a control (weighted mean difference (WMD) 28.07, 95CI: 13.37 to 42.77). Ultrasound to the palmar and dorsal aspects of the hand also appears to have beneficial effects to the following outcome measures: wrist dorsal flexion (WMD 1.90, 95%CI: 0.64 to 3.16), duration of morning stiffness (WMD 28.54, 95%CI: 0.18 to 56.90), number of swollen joints (WMD 1.02, 95%CI: 0.45 to 1.59) and the number of painful joints (WMD 1.20, 95%CI: 0.45 to 1.95). There is no significant difference between a)exercises and wax, b)exercises with ultrasound, c)exercises with ultrasound and faradic hand baths for the following outcome measures: pain score, grip strength, circumference of proximal interphalangeal (PIP) joints, articular index, range of motion or level of activity. REVIEWER'S CONCLUSIONS: The reviewers concluded that ultrasound in combination with the following treatment modalities; exercises, faradic current and wax baths, is not supported and cannot be recommended. Ultrasound alone can however, be used on the hand to increase grip strength, and to a lesser extent, based on the borderline results, increase wrist dorsal flexion, decrease morning stiffness, reduce the number of swollen joints and reduce the number of painful joints. It is important to note that these conclusions are limited by the methodological considerations such as poor quality of the trials, the low number of clinical trials, and the small sample size of the included studies.

Arthritis, Rheumatoid↗

Celecoxib for rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic auto-immune disorder, involving persistent joint inflammation. NSAIDs are used to control the symptoms of RA, but are associated with significant gastro-intestinal toxicity, including a risk of potentially life threatening gastroduodenal perforations, ulcers and bleeds. The NSAIDs known as the selective Cox II inhibitors, of which celecoxib is a member, were developed in order to reduce the GI toxicity, but are more expensive. OBJECTIVES: To establish the efficacy and safety of celecoxib in the management of RA by systematic review of available evidence. SEARCH STRATEGY: We searched the following databases up to August 2002: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references. SELECTION CRITERIA: All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers. Data was analysed using a fixed effects model. A validated checklist was used to score the quality of the RCTs. The planned analysis was to pool, where appropriate continuous outcomes using mean differences and dichotomous outcomes using relative risk ratios. This was not however possible due to the lack of data. MAIN RESULTS: Five RCTs were included (4465 participants); three of the studies also enrolled individuals with OA. The comparators were placebo, naproxen, diclofenac and ibuprofen. The evidence reviewed suggests that celecoxib controls the symptoms of RA to a similar degree to that of the active comparators examined (naproxen, diclofenac and ibuprofen). When compared to placebo, the percentage of patients showing improvement according to ACR 20 criteria at week 4 were 42/82 (51%) in the twice daily celecoxib 200mg group and 43/82 (52%) in the twice daily celecoxib 400mg group; these were significantly different from the placebo group in which 25/85 (29%) improved. The six month data reviewed support a reduced rate of UGI complications with celecoxib but there is also evidence to suggest that these benefits may not be evident in the long-term and that celecoxib offers no additional benefit in patients who are also receiving cardio-prophylactic low dose aspirin. REVIEWER'S CONCLUSIONS: For an individual with RA the potential benefits of celecoxib need to be balanced against the uncertainty that the short-term reduced incidence of upper GI complications are maintained in the long-term and its increased cost in comparison to traditional NSAIDs.

Anti-Inflammatory Agents, Non-Steroidal↗

Therapeutic ultrasound for treating patellofemoral pain syndrome.

BACKGROUND: Therapeutic ultrasound is one of several rehabilitation interventions suggested for the management of pain due to patellofemoral pain syndrome. OBJECTIVES: To assess the effectiveness and side effects of ultrasound therapy for treating patellofemoral pain syndrome. SEARCH STRATEGY: We searched MEDLINE, Embase, Healthstar, Sports Discus, CINAHL, the Cochrane Controlled Trials Register, the PEDro database, the specialized registry of the Cochrane musculoskeletal group and the Cochrane field of physical and related therapies up to December 2000 according to the sensitive search strategy for RCTs designed for the Cochrane Collaboration. The search was complemented with handsearching of the reference lists. Key experts in the area were contacted for further articles. SELECTION CRITERIA: All randomized controlled trials (RCTs) and controlled clinical trials (CCTs), case-control and cohort studies comparing therapeutic ultrasound against placebo or another active intervention in patients with patellofemoral pain syndrome were selected, according to an a priori protocol. DATA COLLECTION AND ANALYSIS: Two reviewers determined the studies to be included based on a priori inclusion criteria (LB, VAR). Data were independently abstracted by the same two reviewers, and checked by a third reviewer (BS) using a pre-developed form. The same two reviewers, using a validated scale, independently assessed the methodological quality of the RCTs and CCTs. The data analysis was performed using Peto Odds ratios. MAIN RESULTS: The search retrieved 85 articles. Of the 8 that were potentially relevant, only one RCT, including 53 patients with patellofemoral pain syndrome, was included. All patients received exercises as a concurrent therapy. Ultrasound combined with ice massage contrast (n=13) was not statistically different from ice massage alone (n=16) in terms of patient-rated pain relief improvement, quadriceps and hamstring strength. In the ultrasound and ice massage group, 46% (6/13) reported improved pain relief compared to 31% (4/13) in the ice massage alone group. This difference of 15% does not meet international standards for clinically important improvement in osteoarthritis of 20%. Side effects were not reported. REVIEWER'S CONCLUSIONS: Ultrasound therapy was not shown to have a clinically important effect on pain relief for patients with patellofemoral pain syndrome. These conclusions are limited by the poor reporting of the therapeutic application of the ultrasound and low methodological quality of the trial included. No conclusions can be drawn concerning the use or non use of ultrasound for treating patellofemoral pain syndrome. More well-designed studies are needed.

Humans↗

Thermotherapy for treating rheumatoid arthritis.

BACKGROUND: Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists. OBJECTIVES: To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis. SEARCH STRATEGY: We searched Medline, Embase, PEDro, Current Contents, Sports Discus and CINAHL up to June 2000. The Cochrane Field of Rehabilitation and related therapies and the Cochrane Musculoskeletal Review Group were also contacted for a search of their specialized registers. Handsearching was conducted on all retrieved articles for additional articles. SELECTION CRITERIA: Randomized or controlled clinical trials of ice or heat compared to placebo or active interventions in patients with rheumatoid arthritis and case-control and cohort studies were eligible. No language restrictions were applied. Abstracts were accepted. DATA COLLECTION AND ANALYSIS: Two independent reviewers identified potential articles from the literature search. These reviewers extracted data using pre-defined extraction forms. Consensus was reached on all data extraction. Quality was assessed by two reviewers using a 5 point scale that measured the quality of randomization, double-blinding and description of withdrawals. MAIN RESULTS: Three studies (79 subjects) met the inclusion criteria. There was no effect on objective measures of disease activity (including inflammation, pain and x-ray measured joint destruction) of either ice versus control or heat versus control. Patients reported that they preferred heat therapy to no therapy (94% like heat therapy better than no therapy). There was no difference in patient preference for heat or ice. No harmful effects of ice or heat were reported. REVIEWER'S CONCLUSIONS: Since patients enjoy thermotherapy, and there are no harmful effects, thermotherapy should be recommended as a therapy which can be applied at home as needed to relieve pain. There is no need for further research on the effects of heat or cold for RA.

Arthritis, Rheumatoid↗

The effects of regular inhaled formoterol, budesonide, and placebo on mucosal inflammation and clinical indices in mild asthma.

The present study was designed to observe the effects of 8 wk of treatment with formoterol (Foradil) 24 microgram, budesonide 400 microgram, and matched placebo inhaled twice a day on inflammatory indices in the bronchial mucosa of 64 patients with mild atopic asthma. Biopsies were obtained at the start and 1 wk before stopping a 9-wk period of treatment, and inflammatory cell numbers were assessed in the submucosa and epithelium by immunohistochemistry. Regular formoterol significantly reduced the number of submucosal mast cells, with a similar trend for eosinophils but not activated T cells. A subgroup analysis conducted in biopsies with >= 10 eosinophils per mm2 revealed a significant reduction in eosinophil numbers when compared with both pretreatment baseline (p < 0.01) and changes after placebo (p < 0.01). Parallel, but less pronounced, effects were observed on mast cell but not on CD25(+) T cell numbers. There was no effect of any of the three treatments on BAL levels of mast cell or eosinophil mediators. We conclude that regular treatment with inhaled formoterol reduces rather than increases inflammatory cells in the mucosa of asthmatic patients. It is possible that these cellular effects of formoterol may contribute to the therapeutic efficacy of this drug when used regularly in the treatment

Administration, Inhalation↗

The poster presentation: what value to the teaching and assessment of research in pre- and post-registration nursing courses?

Poster presentations have proved to be a popular method of displaying information at conferences, and are being used increasingly as a teaching method. Innovative strategies for teaching and assessing research need to facilitate students' achievement of research skills required for practice. These are outlined by the Department of Health, and emphasize the development of research literacy. Using the poster presentation as a teaching and assessing strategy on diploma level courses (Project 2000 and ENB 870 introduction to the Understanding and Application of Research) has proved to be valuable in developing vital research awareness skills and in harnessing enthusiasm for research. Students imply a sense of achievement gained through the process of developing the poster and the production of the poster itself. Herein lies the value of the poster presentation, for it allows the development of crucial research literacy skills which can be widely used in professional practice and future professional education.

Audiovisual Aids↗

Effect of natural allergen exposure during the grass pollen season on airways inflammatory cells and asthma symptoms.

BACKGROUND: Bronchial challenge with allergen causes a specific form of airways inflammation consisting of an influx of neutrophils, eosinophils, and T cells. Because the relevance of the challenge model to clinical asthma is uncertain, the cellular changes that occur in the lungs of asthmatic subjects during natural seasonal allergen exposure were investigated. METHODS: Seventeen grass pollen sensitive asthmatic subjects with previously reported seasonal exacerbations of asthma kept records of symptoms and underwent fibreoptic bronchoscopy with bronchoalveolar lavage (BAL) and endobronchial biopsy before and during the peak of the grass pollen season. The BAL cells were analysed for differential cell counts and by flow cytometry for T cell subsets and surface activation markers. The biopsy samples were processed into glycol methacrylate resin and immunohistochemical analysis was performed for mast cells, activated eosinophils, T cells and interleukin 4 (IL-4), a cytokine with a pivotal role in allergen-induced inflammation. RESULTS: In the pollen season there was an increase in T lymphocyte activation in the BAL fluid as identified by increased expression of interleukin 2 receptor (IL-2R). In the submucosa these changes were paralleled by an increase in CD4+ T cells. By contrast, the numbers of metachromatic cells in BAL fluid staining with toluidine blue were reduced, possibly because of degranulation following allergen stimulation. In keeping with mast cell activation, the number of mucosal mast cells staining for secreted IL-4 increased during the season. In comparison with the period shortly before the onset of the season, all but two subjects experienced an asthma exacerbation which followed the rise in pollen counts but, compared with the period preceding the first bronchoscopic examination, asthma symptoms were not increased during the pollen season. CONCLUSIONS: The data suggest that natural allergen exposure, leading to a clinical exacerbation of asthma, may induce an inflammatory response involving T cells, mast cells and eosinophils. The relationship between allergen exposure, cellular infiltration and activation, and clinical symptoms appears to be complex, with factors other than allergen also contributing to asthmatic activity.

Adult↗

DHEAS as an effective vaccine adjuvant in elderly humans. Proof-of-principle studies.

We have demonstrated that in aged mice, the titer of serum antibody induced against tetanus toxoid correlates with resistance to local paralysis caused by injection of tetanus toxin. Only mice immunized shortly after oral dosing with DHEAS demonstrated high serum antibody titers and complete protection from paralysis. These results became the basis for initiating proof-of-principle studies in human volunteers above age 65 using a licensed influenza vaccine and tetanus toxoid in two independent studies. The use of an oral delivery form of DHEAS before influenza vaccination was associated with a demonstrable increase in the number of individuals with a fourfold increase in HAI titers following vaccination. The overall mean increase in HAI titers was highest in the DHEAS-treated group. The use of DHEAS in the immunization of elderly subjects against tetanus toxoid, while unable to enhance the responses, was not a detriment to antibody response. We conclude that further studies will justify the use of DHEAS as an adjuvant for antigens that represent primary responses in the elderly.

Adjuvants, Immunologic↗

Pulmonary immunopathology of sudden infant death syndrome.

Sudden infant death syndrome (SIDS) is the most common cause of postneonatal mortality in the UK. Pathological investigations have shown evidence suggestive of respiratory obstruction with subsequent hypoxia leading to death. We examined 48 infants who died of SIDS and 30 who died of other, non-pulmonary, causes and identified pulmonary eosinophil and neutrophil leucocytes, mast cells, and T and B lymphocytes by immunocytochemistry. Positively stained cells were counted in the parenchyma and around the bronchi without knowledge of the tissue source. The results showed three times more eosinophils in the lungs of infants who died of SIDS (27.61 vs 7.91 [99% CI 1.76-5.87] cells/mm2 for parenchyma) accompanied by increased T lymphocytes and B lymphocytes. There were more peribronchial mast cells in the SIDS group (22.1 vs 14.7 [1.03-2.10] cells/mm2) and insignificant differences in neutrophils and parenchymal mast cells. There were significant associations between eosinophil, B lymphocyte, and T lymphocyte numbers. These findings provide evidence for an abnormal T lymphocyte-mediated pulmonary inflammatory response in SIDS. Products of eosinophil degranulation can cause epithelial damage and pulmonary oedema, which could cause the respiratory obstruction and hypoxia associated with SIDS.

Cell Count↗