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Biomedical subjects

J M Fitzgerald

Publications and source records attributed to J M Fitzgerald.

At least 19 recordsLinked to original sources

A systematic review of the psychological risk factors associated with near fatal asthma or fatal asthma.

Psychological factors such as anxiety, depressive disorders and/or personality disorders may predispose patients with asthma to near fatal asthma (NFA) or fatal asthma (FA). NFA is defined by an asthma exacerbation resulting in respiratory arrest requiring mechanical ventilation or a pCO(2) >or=45 mm Hg. Most studies have used the case-control study design. Several studies analyzing the effects of psychological factors on the risk of NFA or FA have shown conflicting results. We reviewed all of the literature found by the systematic search done of psychological factors on the risk NFA or FA. A MEDLINE search identified 423 articles between 1960 and March 2006. Seven case-controlled studies were identified following strict applications of the inclusion and exclusion criteria. Due to the significant heterogeneity in the measurement of the psychological factors, a summary statistic was not calculated. The trial characteristics were tabulated and qualitative trends were observed to explain the heterogeneity in the results of the studies. Recommendations on future studies in the field are outlined in detail. Following a systematic assessment of all published studies, we cannot conclude that psychological factors increase the risk of NFA and FA.

Anxiety↗

The assessment and management of patients with acute asthma.

Acute asthma is a common medical emergency that is often poorly assessed and managed. Initial evaluation should include a review of historical factors for identifying high risk patients; appropriate evaluation of the current exacerbation, including an objective assessment of airflow obstruction; and, in parallel, initiation of therapy with controlled oxygen therapy, regular bronchodilator therapy and, in most cases, systemic corticosteroids. There is no benefit in using intravenous (IV) corticosteroids--a single 50 mg oral dose is appropriate. Although there is no significant additional bronchodilator effect with the use of ipratropium bromide or IV magnesium, both modalities have been shown to reduce hospitalisations for moderate to severe exacerbations. There is no role for the routine use of IV aminophylline or beta (beta) agonists in patients presenting with acute asthma. Patients who achieve 60% of their predicted peak expiratory flow (PEF) or 1 sec forced expiratory volume (FEV1) or best can usually be safely discharged. The exacerbation should be taken as an opportunity to review how a patient responded to the particular exacerbation. Were they on appropriate anti-inflammatory therapy? Did they modify the dose of therapy early in the exacerbation? Did they have an action plan? Such deficiencies can usually be managed by facilitated referral to a specialist clinic that ideally has an asthma education programme. The need for long-term anti-inflammatory therapy can be reviewed at this time as well as the potential incremental benefit of the addition of add-on therapy, most likely the use of a long-acting beta agonist.

Acute Disease↗

BCG vaccination and the prevalence of latent tuberculosis infection in an aboriginal population.

SETTING: Estimations of prevalence of latent tuberculous infection (LTBI) are confounded by factors known to influence the results of the tuberculin skin test (TST) such as age, contact history and bacille Calmette-Guerin (BCG) vaccination. Appropriate interpretation of TST results is necessary to ensure LTBI treatment for those at greatest risk. OBJECTIVE: To document the prevalence of LTBI in Aboriginal people living on a reserve in British Columbia (BC) and to determine the influence of BCG. DESIGN: A population-based, retrospective descriptive analysis of all epidemiological data collected for the on-reserve Aboriginal programme in BC (1951-1996). RESULTS: Of 17615 persons who received a TST during the study period, 42% had received BCG. During the study period, an average of 2517 TSTs were completed per year (SD = 1228) among persons with an average age of 26 years (SD = 16). Among all subjects, the average prevalence of LTBI was 25% (95 %CI 24-25). The presence of BCG (OR = 3.1, 95%CI 2.8-3.4) and multiple BCGs (OR = 10.2, 95%CI 7.7-13.6) were both associated with a positive TST. A positive TST was also associated with a shorter duration in years between the most recent BCG and the TST. CONCLUSION: The average prevalence of LTBI in a sequential sample of Aboriginal people living on a reserve in BC was estimated at 25%. BCG, especially in multiple doses, increased the likelihood of a positive TST.

Adolescent↗

Pithomycotoxicosis (facial eczema) in ruminants in the Azores, Portugal.

Outbreaks of pithomycotoxicosis (facial eczema), a hepatogenous photosensitisation caused by the mycotoxin sporidesmin, have affected ruminants in the Azores Islands of Portugal after warm, humid periods during late summer and autumn. Twenty-two outbreaks were recorded in cattle between 1999 and 2001, affecting 11.4 per cent of the animals in the affected herds, and in 2000 there was an outbreak in one sheep flock in which more than 20 per cent of the sheep died. The clinical signs included decreases in milk production, weight loss, photosensitisation and its sequelae, including death. The animals had high activities of gamma glutamyltransferase in their serum, and icterus and severe liver disease, including biliary hyperplasia and fibrosis, were found postmortem. The characteristic spores of the toxigenic saprophytic fungus Pithomyces chartarum were found on grass; all 381 isolates of the fungus were toxigenic for sporidesmin by elisa, and the results were confirmed by high-performance liquid chromatography analysis. Cattle from farms at greatest risk of pithomycotoxicosis were protected by supplementing their concentrate feed with zinc oxide, or using a slow-release intraruminal zinc bolus.

Animals↗

Evaluation of incidental renal and adrenal masses.

Incidental renal or adrenal masses are sometimes found during imaging for problems unrelated to the kidneys and adrenal glands. Knowledgeable family physicians can reliably diagnose these masses, thereby avoiding unnecessary worry and procedures for their patients. A practical and cost-efficient means of evaluating renal lesions combines ultrasonography and computed tomographic scanning, with close communication between the family physician and the radiologist. Asymptomatic patients with simple renal cysts require no further evaluation. Patients with minimally complicated renal cysts can be followed radiographically. Magnetic resonance imaging is indicated in patients with indeterminate renal masses, and referral is required in patients with symptoms or solid masses. The need for referral of patients with adrenal masses is determined by careful assessment of clinical signs and symptoms, as well as the results of screening laboratory studies and appropriate radiologic studies. Referral is indicated for patients with incidental adrenal masses more than 6 cm in greatest diameter. Appropriate laboratory screening tests include the following: a 24-hour urinary free cortisol measurement for patients with evidence of Cushing's syndrome; a 24-hour urinary metanephrine, vanillylmandelic acid or catecholamine measurement for patients with evidence of pheochromocytoma; and a serum potassium level for patients with evidence of hyperaldosteronism.

Adrenal Gland Diseases↗

Massive haemolysis in a group A recipient of a group O peripheral blood stem cell allogeneic transplant.

A 28-year-old man with lymphoblastic lymphoma received G-CSF mobilized stem cells from his HLA identical sister, who had been taking methotrexate for psoriasis until 1 month prior to harvest. The recipient's blood group was A Rh D positive and donor's group O Rh D positive. Engraftment and major haemolysis were evident by day 9. From day 9 to day 13 he received 17 units of blood (approximately 3 L of red cells) at a time when his calculated red cell volume was 1 L. This massive transfusion requirement was not explained by his clinical condition and led us to consider factors that may have influenced the degree of haemolysis. The stem cell graft contained 2.85 x 10(6) CD34+ cells kg(-1) and we speculate there was B cell hyperactivity following the withdrawal of methotrexate in the donor and this went unchecked by the omission of methotrexate in the GVHD prophylaxis of the recipient. We have also considered the phenomenon of bystander haemolysis, previously unreported in this situation, as haemolysis of transfused group O blood must have also occurred. The case also illustrates the importance of transfusing donor type red cells and recipient type fresh frozen plasma (FFP) and platelets into minor mismatched transplant patients. The decision to revert to donor type FFP and platelets should only be made when the direct antiglobulin test is negative and the appropriate isohaemagglutinins are no longer demonstrable.

ABO Blood-Group System↗

The role of the C-C chemokine receptor-5 Delta32 polymorphism in asthma and in the production of regulated on activation, normal T cells expressed and secreted.

BACKGROUND: There are conflicting data regarding the role of a deletion in the C-C chemokine receptor-5 gene (CCR5*D32) in the pathogenesis of asthma and whether this deletion influences the production of regulated on activation, normal T cells expressed and secreted (RANTES). RANTES is a chemokine that is known to play an important role in the pathogenesis of allergic asthma. OBJECTIVE: We sought to determine whether CCR5*D32 is associated with increased RANTES production, the presence of asthma, and the severity of asthma. METHODS: A PCR assay for CCR5*D32 was developed. The prevalence of CCR5*D32 was determined in a group of patients with mild-to-moderate asthma, a group of subjects with severe asthma who had fatal or near-fatal asthma attacks, and a group of nonasthmatic control subjects. The level of RANTES produced by stimulated and unstimulated T cells was measured by using a commercially available immunoassay. RESULTS: The frequency of CCR5*D32 was not significantly increased in the severe asthma group compared with in the mild-to-moderate asthma group. CCR5*D32 was not increased in the asthmatic subjects versus in the control subjects. There was no significant increase in RANTES levels from T cells heterozygous for CCR5*D32 compared with wild-type cells. CONCLUSION: These data indicate that the CCR5*D32 allele is not a genetic risk factor for the development of asthma and does not influence disease severity. The CCR5*D32 allele does not influence RANTES production in the heterozygous state.

Asthma↗

Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity.

BACKGROUND: Genetic polymorphisms have been associated with asthma and asthma severity. OBJECTIVE: We sought to determine whether 3 polymorphisms were associated with severe asthma indicated either by the occurrence of a fatal (or near-fatal) asthma attack or by severe airflow obstruction. METHODS: We obtained DNA and clinical data from asthmatic subjects who either died or nearly died during an asthma attack and from a group of subjects with mild-to-moderate asthma who had never experienced a fatal or near-fatal asthma episode. These groups were compared with a group of nonatopic nonasthmatic control subjects. The level of airflow obstruction (FEV(1) percent predicted) in the subjects with mild-to-moderate asthma was used as an additional measure of disease severity. The subjects were genotyped for the IL4*C-589T promoter polymorphism and the IL4RA*Q576R and the FCERIB*E237G amino acid substitutions. RESULTS: The results showed that the FCERIB*E237G and IL4RA*Q576R polymorphisms were not associated with fatal or near-fatal asthma. However, the IL4*-589T allele was significantly increased in the subjects with fatal or near-fatal asthma compared with nonasthmatic subjects (odds ratio [OR], 1.8; P =.02) and subjects with mild-to-moderate asthma (OR, 1.9; P =.02). There was no interaction between the IL4*-589T and IL4RA*576R alleles. Of the 3 polymorphisms, only the IL4RA*576R allele was associated with severe airflow obstruction (OR, 8.2; P =.01). CONCLUSION: These data suggest that the IL4*-589T allele is a risk factor for life-threatening asthma and that the IL4RA*576R allele is a risk factor for a low level of lung function in asthmatic subjects.

Airway Obstruction↗

Younger and older jurors: the influence of environmental supports on memory performance and decision making in complex trials.

This study compared memory and decision making by younger (aged 19-35) and older (aged 55-75) adults who had viewed a 2-hr video of a complex civil trial. Participants were tested for free recall, recognition memory, source identification, and the accuracy of their verdicts. The experiment manipulated (a) note taking during the trial and (b) timing of judicial instructions: either before (preinstructed) or after (standard) the presentation of relevant evidence. Judicial instructions provide jurors with a framework for understanding legal concepts such as liability and compensatory damages. Both younger and older adults provided more detailed and cohesive accounts when they were given judicial instructions before the evidence. Other benefits of preinstruction to memory and decision making were limited to older adults. Note-taking effects were generally limited but were consistent across age groups. The results highlight the potential value of relatively simple interventions for improving cognitive performance in a real-world setting.

Adult↗

Prevalence of tumor necrosis factor-alpha and angiotensin converting enzyme polymorphisms in mild/moderate and fatal/near-fatal asthma.

Allele 2 of the polymorphism at position -308 in the promoter of the tumor necrosis factor alpha (TNF-alpha) gene, and the D allele of the angiotensin converting enzyme (ACE) gene, have been associated with asthma. We hypothesized that genotypes containing these alleles would show an increased prevalence in asthmatic as compared with nonasthmatic individuals, and would be associated with asthma severity. Polymerase chain reaction-based assays were developed to determine TNF-alpha and ACE genotypes among subjects with mild/moderate asthma (n = 92), fatal/near-fatal asthma (n = 159), no asthma (n = 43), and random population controls (n = 252). The TNF-alpha -308 polymorphism was increased in both subjects with mild/moderate (p = 0.03) and those with fatal/near fatal asthma (p = 0.02) versus those without asthma, and in all subjects with asthma versus random population controls (p = 0.02). The mild/moderate group was subdivided into subjects with mild (n = 43) and those with moderate (n = 33) asthma. TNF-alpha -308 was increased in the moderately asthmatic versus the nonasthmatic subjects (p = 0.003), and in the mildly asthmatic subjects (p = 0.01). However, TNF-alpha -308 was not significantly more prevalent in the fatal/near-fatal than in the mild/moderate asthmatic group. The ACE-D allele did not show an association with either asthma or asthma severity. We conclude that the TNF-alpha -308 polymorphism may be a risk factor for asthma but does not increase the risk of a fatal or a near-fatal asthma attack, whereas the ACE polymorphism is not associated with asthma in this population.

Adult↗

Biological control of sporidesmin-producing strains of Pithomyces chartarum by biocompetitive exclusion.

The feasibility of using atoxigenic strains of Pithomyces chartarum for the biological control of toxigenic strains of P. chartarum was examined. Pasture, treated with atoxigenic strains of P. chartarum, contained up to 80% less sporidesmin than found in untreated pasture. Maximum sporidesmin levels of 26 ng g-1 grass in treated pasture and 113 ng g-1 grass in untreated pasture (means of 24 and four plots, respectively) were recorded 14 weeks after treatment, when spore numbers had reached a maximum of 80,000 spores g-1 grass in the untreated plots and 50,000 spores g-1 grass in the treated plots. This trial demonstrated that sporidesmin-producing spores of P. chartarum could be successfully reduced in pasture by the addition of atoxigenic strains, thereby reducing the risk of facial eczema in livestock.

Animals↗

A randomized trial comparing peak expiratory flow and symptom self-management plans for patients with asthma attending a primary care clinic.

Great emphasis is placed on educating asthmatics to use action plans to achieve better control of symptoms. The use of peak flow meters (PFM) has been recommended as an important part of self-management plans. We studied 92 (47 F) adult patients with asthma in a primary care setting to compare the effectiveness of action plans using either peak flow monitoring or symptoms to guide self-management. Each patient was instructed in the use of the action plan in the context of a 6-mo asthma education program taught by a nurse. Patients were already using inhaled corticosteroids or were newly prescribed corticosteroids by their family physician. Forty-four patients were randomized to the PFM group and 48 to the symptoms group. Spirometry, symptom scores, quality of life, medication use, and measures of health care utilization and morbidity (emergency department visits, hospitalizations, unscheduled doctor visits, and days lost from work or school) were recorded at baseline and throughout the study period. PC20 methacholine was measured at the first and at the final visits. There were significant improvements within groups for FEV1, symptoms score, PC20 methacholine, and quality of life, but no between-group differences. A significant shift from higher to lower daily use of beta-agonists (p < 0.008 for both groups) and significant shifts to higher daily doses of inhaled steroids (p < 0.001) occurred in each group. Adherence to the self-management plans was only 65% in the PFM group and 52% in the symptoms group. Outcomes for health care utilization were similar except for fewer patients making unscheduled doctor visits within the PFM group. Our findings show that education, regular follow-up, and an action plan are effective in improving asthma control and quality of life, but the routine use of PFM to guide interventions is not the only way to accomplish these objectives.

Adult↗

Risk factors for near-fatal asthma. A case-control study in hospitalized patients with asthma.

We prospectively recruited patients admitted to the hospital with severe asthma to comprehensively evaluate the association of historical and physiologic features with the risk of near-fatal asthma (NFA). A case-control study design was used. All patients admitted with NFA (cases) were identified prospectively and compared with asthma patients admitted during the same period without respiratory failure (controls). Nineteen cases (age: 40.2 +/- 12.0 yr) (mean +/- SD) and 80 controls (age: 36 +/- 13.5 yr) were enrolled. Duration of asthma, gender, smoking status, ethnicity, and prevalence of atopy were similar in the case and control groups. More than 80% of patients in both groups reported worsening symptoms for more than 48 h before admission, and more than 50% were worse for longer than 7 d. There was no difference in degree of airways obstruction or bronchial hyperresponsiveness (PC20). Perception of dyspnea was similar in the cases and controls, but among cases the males had greater impairment than the females (Borg score: 1.9 +/- 1. 4 versus 3.9 +/- 1.2: p = 0.05). Univariate analysis identified a history of previous mechanical ventilation (OR: 27.5; 95% CI: 6.60 to 113.7), admission to the intensive care unit (ICU) (OR: 9.9; 95% CI: 3.0 to 32.9), history of worse asthma during January and February (OR: 3.5; 95% CI: 1.0 to 11.8), and use of air-conditioning (OR: 15.0; 95% CI: 1.3 to 166) as risk factors for NFA. Of concern was the dependence of most patients (59.8%) on the emergency department (ED) for initial care, and the small number of cases (16%) in which patients visited a physician before admission to the hospital. We have confirmed risk factors identified previously in retrospective studies of fatal and NFA, and have also shown that hospitalized patients with asthma, irrespective of severity of their asthma, share several characteristics, especially in terms of their failure to respond to worsening asthma.

Acute Disease↗

beta2-Adrenergic receptor haplotypes in mild, moderate and fatal/near fatal asthma.

Excess beta2-agonist use in asthmatics has been associated with increased mortality and morbidity. The mechanisms responsible for these observations are unknown. We hypothesized that polymorphisms of the beta2-adrenergic receptor (beta2AR) at amino acid positions 16, 27, and 164, which are known to alter receptor functions in vitro, may predispose asthmatics to fatal/near-fatal asthma and/or modify asthma severity. In preliminary studies we found significant differences in allele frequencies due to ethnic background: Caucasian, Black, Asian Gly16 = 0.61, 0.50, 0.40 and Gln27 = 0.57, 0. 73, 0.80, respectively. beta2AR genotyping was performed on DNA from Caucasians classified as nonasthmatic/nonatopic (n = 84), fatal/near-fatal asthmatics (n = 81) and mild/moderate asthmatics (n = 86). No polymorphism or haplotype was found to be associated with fatal/near-fatal asthma. However, the Gly16/Gln27 haplotype, which undergoes enhanced downregulation in vitro, was substantially more prevalent in moderate asthmatics than in mild asthmatics (p = 0.003, odds ratio = 3.1). We conclude that the beta2AR genotype is not a major determinant of fatal or near-fatal asthma. Furthermore, allele frequency variation among ethnic groups must be considered in clinical studies of beta2AR polymorphisms in asthma.

Adrenergic beta-Agonists↗

The effect of adding ipratropium bromide to salbutamol in the treatment of acute asthma: a pooled analysis of three trials.

OBJECTIVE: To assess the effect on FEV1 and clinical outcomes of adding ipratropium bromide to salbutamol in the treatment of acute asthma. METHODS: We conducted a pooled analysis of three randomized double-blinded clinical trials conducted in the United States, Canada, and New Zealand. The studies enrolled 1,064 patients aged 18 to 55 years who presented at the emergency department with acute asthma. Patients were randomized to treatment with a combination of nebulized 2.5 mg salbutamol plus 0.5 mg ipratropium bromide, or 2.5 mg salbutamol alone. Medications were administered at baseline and, in the US study, at 45 min. FEV1 was measured at baseline, 45 min, and 90 min. Patients were followed up for 48 h after hospital discharge for occurrence of asthma exacerbation and hospitalization. RESULTS: Treatment groups were comparable at baseline. Of the 1,064 patients randomized, 1,015 patients (95%) remained in the study for measurement at 45 min, and 961 patients (90%) completed the final measurement at 90 min. Comparison of overall improvement in FEV1 at 45 min indicated a better response for patients receiving combination therapy (mean difference=43 mL, 95% confidence interval [CI]=-20, 107). The distribution of change in FEV1 was skewed by a small number of patients with extreme values (38 of 1,064=3.6%) that may have been due to unreliable lung function testing. Removing these outliers produced a larger and more precise estimate of effect (mean difference=55 mL, 95% CI=2,107). Because the distribution was skewed, we performed nonparametric analyses that showed evidence of a beneficial effect of combination therapy. The difference between median values at 45 min is 40 mL (Wilcoxon p value=0.03). In addition, 4.9% (95% CI=-1%, 11%) more patients in the combination group achieved at least 20% of their potential improvement, as measured by the difference between their baseline FEV1 and their predicted FEV1. Patients receiving combination therapy had lower risk for each of three clinical outcomes: the need for additional treatment (relative risk [RR]=0.92, 95% CI=0.84, 1.0), risk of asthma exacerbation (RR=0.84, 95% CI=0.67, 1.04), and risk of hospitalization (RR=0.80, 95% CI=0.61, 1.06). CONCLUSION: Adding ipratropium bromide to salbutamol in the treatment of acute asthma produces a small improvement in lung function, and reduces the risk of the need for additional treatment, subsequent asthma exacerbations, and hospitalizations. These apparent benefits of adding ipratropium bromide were independent of the amount of beta-agonist that had been used earlier in the attack, and possibly related to a recent upper respiratory tract infection. Confirmatory studies are needed, especially for clinical outcomes.

Acute Disease↗

Development of PCR-SSOP for the identification of HLA-A*02 subtypes and determination of HLA-A*02 frequencies within different ethnic populations.

A PCR-SSOP typing method, involving a single PCR amplification in conjunction with 19 digoxigenin labelled oligonucleotide probes, has been developed for the identification of 17 known HLA-A*02 alleles. The method has been applied to four populations (Northern Ireland, Singapore Chinese, Shetland Island and Mexican) and percentages of HLA-A*02 alleles determined within each population.

Alleles↗