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Biomedical subjects

J A Douglass

Publications and source records attributed to J A Douglass.

16 recordsLinked to original sources

Anaphylaxis to Gelofusine confirmed by in vitro basophil activation test: a case series.

The plasma expander Gelofusine (succinylated gelatin) is a recognised cause of peri-operative anaphylaxis. Current diagnosis of Gelofusine sensitivity is by skin testing, a procedure that itself carries a risk of allergic reaction. We evaluated the reliability of the in vitro basophil activation test as a diagnostic assay for Gelofusine sensitivity in subjects with a clinical history highly suggestive of Gelofusine allergy. Six patients with peri-operative anaphylaxis clinically attributed to Gelofusine were skin tested to confirm sensitivity. Control subjects included three healthy subjects and five subjects allergic to a neuromuscular blocking drug, all negative on Gelofusine skin testing. Whole blood basophil activation to Gelofusine was analysed by flow cytometry for CD63 surface expression. All of the Gelofusine sensitive patients and one of the control allergic subjects showed positive basophil activation to Gelofusine. In this series of subjects, the basophil activation test for Gelofusine allergy had a sensitivity of 100% and a specificity of 87.5%. Our findings suggest that basophil activation testing is a safe and reliable in vitro assay for prediction or confirmation of Gelofusine sensitivity in patients with high clinical suspicion of Gelofusine-induced anaphylaxis.

Aged↗

Parity and decreased use of oral contraceptives as predictors of asthma in young women.

BACKGROUND: Asthma is more prevalent among males in childhood, but females report higher rates in adulthood. The reasons are unknown; although it has been hypothesized that hormonal factors may explain this sex-dependent risk of adult-onset asthma. OBJECTIVE: To determine whether a woman's reproductive history or use of oral contraceptives is associated with adult-onset asthma. METHODS: In 1991-1993, we surveyed 681 women aged 29-32 years randomly sampled from participants first surveyed at age 7 years by the 1968 Tasmanian Asthma Survey, a study of all children born in 1961 and attending school. Current asthma was defined as reporting asthma or wheezy breathing in the past 12 months. RESULTS: In women who did not have asthma or wheezy breathing by age 7 years, 13% had current asthma. The risk of current asthma in these who were parous increased with the number of births (odds ratio (OR) 1.50 per birth, 95% confidence interval (CI) 1.01-2.23 P=0.04) while women with one birth were at a lower risk than nulliparous women (OR 0.46 95% CI 0.2-1.06, P=0.07). Independent of parity, the risk decreased by 7% (95% CI 0-13%) per year of oral contraceptive pill use in all women. In women who did have asthma or wheezy breathing by age 7 years, neither reproductive history nor oral contraceptive pill use predicted current asthma. CONCLUSION: Our observation that parity and decreased oral contraceptive use predict asthma in women, is consistent with the hypothesis that the asthma that develops after childhood is in part a response to endogenous and exogenous female hormones. This may be due to alterations of cytokine responses by the pregnant state, triggering adult-onset asthma in women.

Adult↗

Asthma 3+ Visit Plan: a qualitative evaluation.

INTRODUCTION: The Asthma 3+ Visit Plan is a Commonwealth primary care initiative to improve care for patients with moderate or severe asthma through visits to general practitioners (GP). AIMS: To assess the use of, and barriers to, completing the Asthma 3+ Visit Plan in recurrent emergency department attendees; asthma knowledge, symptoms and quality of life were assessed before and after undertaking the plan. METHODS: The design was a predominantly qualitative study. Consenting individuals who presented for emergency treatment for asthma were interviewed before and after completing the Asthma 3+ Visit Plan with their GP. Asthma knowledge, symptom control, quality of life and demographic information were collected and participants underwent in-depth interviews for qualitative analysis. The setting was a tertiary teaching hospital and two suburban hospitals. The participants were 20 recurrent emergency attendees with asthma. RESULTS: Individuals who completed the Asthma 3+ Visit Plan had significant improvements in asthma-related quality of life and asthma knowledge. Qualitative interviews revealed that recurrent emergency attendees for asthma viewed the Asthma 3+ Visit Plan favourably. A good relationship with the GP appeared integral to the success of the Asthma 3+ Visit Plan and patient recall was an important factor in plan completion. Cost was also a barrier to patients completing the plan. CONCLUSION: Our findings support the Asthma 3+ Visit Plan as a discharge strategy for recurrent emergency attendees with asthma.

Adolescent↗

Induction of T 'regulatory' cells by standardized house dust mite immunotherapy: an increase in CD4+ CD25+ interleukin-10+ T cells expressing peripheral tissue trafficking markers.

BACKGROUND: Clinically effective subcutaneous allergen-specific immunotherapy (SIT) is associated with altered circulating T cell cytokine production and altered local cytokine responses with increased IL-10 following allergen challenge in target organs. OBJECTIVE: This study aimed to elucidate mechanisms for these T cell changes, by examining surface expression of markers for peripheral tissue trafficking on circulating cytokine-positive T cells following standardized house dust mite- (HDM-) SIT. METHODS: A randomized conventional HDM immunotherapy study was performed on a panel of 12 HDM-allergic subjects. Nine subjects received treatment with conventional HDM immunotherapy using a standardized extract and three subjects were treated by standard pharmacotherapy alone. Symptom and medication scores and allergen-induced cutaneous late-phase responses were assessed before and 9 months after institution of therapy. Before and at 3 and 9 months of SIT, peripheral blood mononuclear cells were cultured for 14 days with HDM extract and CD4+ and CD8+ T cell expression of CD62L, CD49d and CCR5 and production of IL-10, IFN-gamma and IL-4 were analysed by flow cytometry. Allergen-specific T cell proliferation was assessed by 3H-thymidine incorporation. RESULTS: At 9 months, all SIT-treated patients showed reduced symptom scores and late-phase cutaneous responses to HDM compared with baseline levels. The proportions of CD4+ T cells which were IL-10+ were increased (P < 0.01), and the proportions of CD4+ and CD8+ T cells which were IL-4+ decreased (P < 0.05) compared with baseline. CD4+ and CD8+ T cell IFN-gamma production, expression of surface markers for peripheral tissue trafficking and allergen-specific proliferation remained unchanged during SIT treatment. However, increased proportions of CD4+CD62L(-), CD4+CD49d(hi), CD4+CCR5+ T cells expressing IL-10 were detected at 9 months of SIT compared with baseline (P < 0.05). IL-10 staining co-localized with CD4+CD25+ T cells. CONCLUSION: Clinically effective subcutaneous immunotherapy with a standardized HDM Dermatophagoides pteronyssinus preparation results in decreased numbers of IL-4+ T cells and expansion of CD4+IL-10+ T cells expressing a peripheral tissue trafficking phenotype. The co-localization of IL-10+ staining to CD4+CD25+ T cells is consistent with the induction of a T regulatory cell population by SIT.

Adult↗

Short-term efficacy of ultrasonically nebulized hypertonic saline in cystic fibrosis.

Progressive lung disease in patients with cystic fibrosis (CF) is caused by thick secretions, which cause airway obstruction and subsequent colonization and infection by inhaled pathogenic microorganisms. Recently, recombinant human DNase has been shown to reduce the viscoelasticity of sputum in patients with cystic fibrosis and to improve lung function. Ultrasonically nebulized hypertonic saline (HS) has been demonstrated to enhance mucociliary clearance and sputum expectoration by rehydrating airway secretions, and may therefore provide a low cost alternative. We studied the changes in pulmonary function and symptoms in a group of patients with CF who have moderate to severe lung disease. The patients were evaluated following 2 weeks of treatment with HS in an open-label study. Subjects were randomly allocated to receive 10 ml of either 0.9% NaCl (IS) or 6% NaCl (HS). Twice daily, prior to physiotherapy, treatments were delivered by a portable ultrasonic nebulizer. To prevent bronchoconstriction, 600 mg of salbutamol was administered prior to the nebulized solutions. A symptom score was recorded and spirometry was performed on day 0 before therapy was started, on day 14 (the last day of therapy), and on day 28 (14 days after the last treatment with either IS or HS). Fifty-two patients (32 males), with a mean age of 16.2 (range 7-36) years completed the study. There was no difference in baseline characteristics between the two groups. Following 2 weeks of treatment, there was a significant improvement from baseline in FEV1 of 15.0 +/- 16.0% (mean +/- SD) in patients treated with HS, compared with a change of 2.8 +/- 13% in those on IS therapy (P = 0.004). Furthermore, there was a subjective improvement in the effectiveness of chest physiotherapy as reported by those using HS (P = 0.02). The treatment was well tolerated. We conclude that in patients with CF, ultrasonically nebulized hypertonic saline improves lung function in a way similar to that reported for human recombinant DNase when inhaled over a 2 week period. Nebulized saline also enhances the perception of effectiveness of chest physiotherapy.

Administration, Inhalation↗

HIV-1 proviral DNA copy number in peripheral blood leucocytes and bronchoalveolar lavage cells of AIDS patients.

In this study we have determined by polymerase chain reaction (PCR) the quantity of HIV-1 proviral DNA in cells obtained by bronchoalveolar lavage (BAL) from the lung of HIV-1+ individuals. This has been compared quantitatively with the proviral DNA in peripheral blood leucocytes (PBL) obtained simultaneously from the same patients. The mean HIV DNA copy number per 10(6) cells was 391 for PBL, with a range of 1-9000, and 2971 for BAL cells, with a range of < 1-70,000. The quantity of HIV DNA detected in BAL cells was higher than that detected in the corresponding PBL samples in 44 out of 78 (56%) individuals, whilst more HIV DNA was detected in the PBL compared with BAL cells in 14 out of 78 (18%) patients. In both BAL and PBL higher levels of HIV DNA were detected in the adherent (monocyte/macrophage) enriched cell populations compared with other non-adherent cells (leucocytes). A direct relationship between HIV DNA copy number and ability to recover infectious HIV progeny in vitro by co-cultivation with cord blood leucocytes was found for both PBL and BAL cells. Individuals known to be receiving azidothymidine treatment had a lower mean HIV DNA load in all cell fractions compared with those patients on no antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

Influence of interleukin-8 challenge in the nasal mucosa in atopic and nonatopic subjects.

Interleukin-8 (IL-8) is a major cytokine in the recruitment of neutrophils (polymorphonuclear leukocytes) to areas of inflammation. It also activates T lymphocytes and cytokine-primed basophils and eosinophils and therefore may be implicated as an effector in allergic inflammation. IL-8 has also been identified as a mediator in such inflammatory pulmonary conditions as cystic fibrosis, allergen challenge, and sarcoidosis. To investigate the bioactivity of IL-8 in humans, we examined the effects of nasal challenge with human recombinant IL-8 in a double-blind placebo-controlled crossover study in which nasal resistance and rhinitic symptoms were monitored for 4 h after challenge. Cellular infiltration was quantified on differentially stained nasal smears obtained at hourly intervals. Cellular responses caused by in vivo priming were assessed by a comparison of atopic and nonatopic patient groups. A significant neutrophilic infiltrate in smear samples was observed in all patients challenged with IL-8 from 12 +/- 4% (mean +/- SEM) at baseline to 60 +/- 6% after 4 h; placebo challenge resulted in an increase in neutrophils to 30 +/- 4% (p < 0.04). Additionally, a significant increase in cumulative eosinophil recruitment occurred over the challenge period. Nasal resistance was significantly increased 10 min after instillation of IL-8 in all subjects compared with placebo, but there was no difference between atopic and nonatopic subjects. Nasal rhinitic symptoms were also increased in all subjects receiving IL-8 compared with placebo. In a further study in 19 subjects, nasal biopsy was performed 3 h after IL-8 or placebo challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Myopathy in severe asthma.

Myopathy complicating the therapy of severe asthma has been recently described in several case reports. Twenty-five consecutive patients admitted to the intensive care unit (ICU) at this hospital for mechanical ventilation for severe asthma were studied for the incidence of creatine kinase (CK) enzyme rise and for the development of clinical myopathy. Pharmacologic therapy was standardized, every patient receiving corticosteroids and aminophylline intravenously and salbutamol both nebulized and intravenously. Twenty-two patients received muscle relaxant therapy with vecuronium. In 19 of 25 (76%) of patients there was elevation of CK levels to a median of 1,575 U/L (range, 66 to 7,430) occurring 3.6 +/- 1.5 days after admission. In nine patients there was clinically detectable myopathy. The presence of either myopathy or CK enzyme rise was associated with a significant prolongation of ventilation time. Arterial blood gas measurements on admission to the ICU revealed a pH (mean +/- SD) of 7.07 +/- 0.21, a PaCO2 of 87.2 +/- 32.7, and a PaO2 (with a high FIO2) of 129 +/- 97 mm Hg; however, no correlation was found between the severity of initial metabolic disturbance and the subsequent development of myopathy. There was no association between the type of corticosteroid administered and the subsequent development of myopathy. Patients with myopathy had received a significantly higher total dose of vecuronium when compared with those who did not develop myopathy (p < 0.001, Kruskal Wallis test). We have therefore found a surprisingly high incidence of CK enzyme rise and myopathy in this group of mechanically ventilated patients with severe asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Improved rapid slide agglutination test for presumptive diagnosis of canine brucellosis.

A modified rapid slide agglutination test for the presumptive identification of Brucella canis infection in dogs has been developed. The method required mixing 0.1 ml of canine serum with 0.1 ml of 0.2 M 2-mercaptoethanol solution. Equal volumes (0.05 ml) of the treated serum and the B. canis plate antigen were mixed. Agglutination results were read within 2 min. Clinical studies showed 100% agreement between this method and the conventional 2-mercaptoethanol tube agglutination test. Excellent correlation was shown between cultural isolation and the modified rapid slide agglutination test, using sera from experimentally infected dogs.

Agglutination Tests↗