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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
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1995

Identification of H-ras mutations in urine sediments complements cytology in the detection of bladder tumors.

BACKGROUND: Urinary cytology has long been used as a noninvasive screen for the detection of urinary tract cancer but is limited by the generation of false positive and false negative results. More recently, molecular changes associated with urothelial neoplastic progression have been identified in DNA from urine sediments, demonstrating an alternative approach for identifying neoplastic change in the bladder. PURPOSE: The purpose of this prospective study was to determine the value of detection of H-ras (also known as HRAS) mutations in urine sediment DNA as a clinical indicator of tumor presence, recurrence, and/or progression. METHODS: Urine sediments were collected from 100 patients presenting with bladder tumors, with follow-up samples collected from 19 patients. DNA extracted from urine sediments was analyzed for changes in exon 1 of the H-ras gene, using single-strand conformation polymorphism (SSCP) analysis. A representative number of aberrant H-ras/SSCP migrating bands were excised and sequenced to confirm the presence of a mutation. Human bladder specimens were obtained from patients (93 of the 100 patients initially and 18 of the 19 patients studied by follow-up) and histologically evaluated for tumor content and grade. RESULTS: Mutations in exon 1 of the H-ras gene were detected in urine sediments from 44% (44 of 100) of the patients; concordant results were obtained by cytologic analysis, where 33% (31 of 93) of the patients displayed positive cytology. Analysis of the distribution of abnormalities with tumor grade revealed greater detection of low-grade (1-2) lesions using ras analysis (47%) compared with cytology (16%). In contrast, cytology was more effective in identifying the presence of carcinoma in situ. Combined results from these two approaches substantially increased the sensitivity of tumor detection, resulting in the identification of tumors in 60% of patients. CONCLUSIONS: Identification of H-ras mutations in DNA from urine sediments facilitates the detection of low-grade bladder tumors and, in combination with cytology, increases the overall tumor detection from 33% to 60%. Preliminary results in patient follow-up suggest that detection of H-ras mutations may have some clinical utility in detecting the presence of abnormal cells in the absence of an overt lesion following cystoscopy or positive cytology.

Base Sequence↗
PubMed1995

Human bladder carcinoma cell lines as indicators of oncogenic change relevant to urothelial neoplastic progression.

Analysis of human tumour-derived cell lines has previously resulted in the identification of novel transformation-related elements and provided a useful tool for functional studies of different genes. To establish the utility of such cell lines as indicators of change relevant to urothelial cancer, we have characterised the expression of five genes (p53, MDM2, Rb, E-cadherin, APC) within a panel of human bladder carcinoma cell lines. Using single-strand conformation polymorphism (SSCP) and direct sequencing, p53 mutations were identified in 7/15 (47%) cell lines reflecting events reported in bladder tumours. Immunohistochemical analysis of p53 in cultured cells and in paraffin-embedded sections of xenografts from the cell line panel revealed discordant results. An absence of p53 nuclear staining was associated with an exon 5 mutation in EJ and with multiple p53 mutations found in J82. Two cell lines positive for p53 staining in the absence of detectable mutation displayed overexpression of MDM2 (PSI, HT1197) in Western blot analysis. Loss or aberrant Rb expression was recorded in 5/15 (TCCSUP, SCaBER, 5637, HT1376, J82) cell lines. Absence of E-cadherin was recorded in 5/15 cell lines (TCCSUP, EJ, KK47, UM-UC-3, J82) with loss of alpha-catenin in immunoprecipitated E-cadherin complexes of CUBIII. Western blot analysis of APC revealed a truncated protein in 1/15 (CUBIII) cell lines. The characterisation of oncogenic events within this panel of human bladder carcinoma cell lines establishes a representation of change observed in bladder tumours and better defines the genotypic background in these experimental human cell models of neoplastic progression.

Base Sequence↗
PubMed1995

Tuberculosis in the 1990s. Issues for primary care physicians.

After declining for many years, tuberculosis rates have begun to level off in Canada. Groups at particularly high risk include aboriginal Canadians, immigrants from high-prevalence countries, HIV-infected people, and elderly men. If disease is suspected, appropriate investigations, including sputum tests for bacteriology and chest x-ray examinations, should be done. Response to treatment is excellent. Chemoprophylaxis is recommended for certain patients. Vaccination with BCG has a limited but important role, especially for aboriginal Canadians.

Canada↗
PubMed1994

A mathematical model for the prediction of the impact of HIV infection on tuberculosis.

A mathematical model is introduced to study the accelerating impact of HIV infection on the incidence rates of tuberculosis (TB) disease. A sexually active population (15-49 years) is followed cross-sectionally over a period of time. Beginning with the year in which HIV infection was probably first present in the population, the model calculates the growing yearly incidence rates of new TB disease in HIV-positive and in HIV-negative individuals. Model equations, derived by an actuarial method, are developed recursively. Input information required for the calculations includes the age distribution of the study population, pre-HIV annual TB infection rates, annual HIV infection and mortality rates, and estimates of annual TB disease breakdown rates in the absence and in the presence of HIV infection. With correct input data, the model provides a useful blueprint for health agencies in designing effective programmes for curbing the future course of these dual epidemics in the population.

AIDS-Related Opportunistic Infections↗
PubMed1993

The combination of hydroxyurea and leucapheresis in the treatment of chronic myeloid leukaemia in pregnancy.

Treatment of malignancy during pregnancy is difficult because of the potential teratogenicity of chemotherapeutic agents. Leucapheresis was employed in the initial management of a pregnant patient with chronic myeloid leukaemia. It was subsequently replaced with oral hydroxyurea during the second trimester. Successful delivery of a live male infant was achieved and the child has normal growth and development to date.

Adult↗
PubMed1992

An estimate of the future size of the tuberculosis problem in sub-Saharan Africa resulting from HIV infection.

The impact of the human immunodeficiency virus (HIV) on tuberculosis is well documented. Its effect in populations with a high proportion of dually infected individuals is likely to be significant. Sub-Saharan Africa is one such region and to better document the effect of HIV infection on tuberculosis there we developed a mathematical model to predict the likely extra numbers of tuberculosis cases due to it. A mathematical model was developed using a variety of scenarios giving a range of risks for the period 1980-2000. The four scenarios included (1) a low rate of 1% risk of tuberculosis infection in year 0 (1980) with 45% tuberculosis infection prevalence, and an HIV prevalence of 2% in 1989; (2) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence, and a 2% HIV prevalence in 1989; (3) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence, and a 10% HIV prevalence in 1989; and (4) a 2% risk of tuberculosis infection in year 0 with 60% tuberculosis infection prevalence and a 20% HIV prevalence in 1989. Under scenarios 1 and 2, a 50-60% increase in smear-positive rates in the subpopulation (15-45 years old) is predicted for the year 2000, under scenario 3, smear-positive rates in the subpopulation in the year 2000 are expected to increase four-fold from the 1980 baseline. Under scenario 4, a 10-fold increase in smear-positive rates in 2000 is expected in the subpopulation. Under this scenario, total disease will have increased 12-fold in the subpopulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Incorrect positioning of nasogastric feeding tubes and the development of pneumothorax.

The authors describe 12 patients in whom feeding tubes were inadvertently placed in the bronchial tree a total of 14 times. All but four of the misplacements were complicated by pneumothorax. No deaths were directly attributable to the misplacements, although one cardiac arrest occurred as a late complication of intrapleural feeding. Careful, controlled insertion of feeding tubes and radiographic confirmation of their placement are essential to reduce morbidity and mortality.

Aged↗