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Biomedical subjects

A B Breslin

Publications and source records attributed to A B Breslin.

At least 19 recordsLinked to original sources
PubMed2000

Obstructive sleep apnea and gastroesophageal reflux.

A number of recent studies have described the presence of significant gastroesophageal reflux (GER) in patients with obstructive sleep apnea (OSA). The aims of our studies were to determine the prevalence of this in a controlled population and to investigate the potential for a causal relationship between the two entities by determining whether therapy of OSA altered GER parameters, and vice versa. All patients presenting to our sleep laboratory for screening polysomnography underwent distal esophageal pH monitoring simultaneously with polysomnography. Control subjects were selected if the apnea-hypopnea index (AHI) was <5.0, and patients were selected if AHI was >15.0. Fourteen subjects with OSA undertook a second polysomnographic study including distal esophageal pH monitoring, with nasal continuous positive airway pressure (nCPAP) intervention. Twelve subjects with proven OSA took part in a randomized, placebo-controlled, double-blinded, parallel group study of the effect of antireflux therapy (nizatidine) on OSA parameters. In 63 patients and 41 controls, we found that patients with OSA had significantly more GER events than controls as measured by number of reflux events over 8 hours (115 vs 23; P <0.001), and percent of time spent at pH <4.0 (21.4% vs 3.7%; P <0.001). In patients with proven OSA, 53.4% of GER episodes were temporally related to apneas or hypopneas. Less than half (46.8%) of all apneas were temporally related to acid reflux, and only 43.8% of arousals were related to reflux events. In the therapeutic trials, nCPAP reduced GER parameters in both patients with OSA and without OSA, suggesting a nonspecific effect. Antireflux therapy (nizatidine) reduced arousals but not apnea-hypopnea index in patients with OSA. Patients with OSA have a higher prevalence of GER than matched control subjects. Nasal CPAP reduces GER parameters nonspecifically, and thus the role of OSA in the pathogenesis of GER remains unclear. GER, however is likely to be important in the pathogenesis of arousals, but there is no evidence that it is involved in the pathogenesis of apneas.

Aged↗
PubMed1997

The patient with chronic cough.

The most effective management of cough is specific therapy, which results in a greater than 90% response rate, so the cause should be thoroughly investigated. A chest x-ray should be taken early in the clinical investigation of chronic cough. The three most common causes of chronic cough when chest x-rays are normal are postnasal drip, bronchial asthma and gastro-oesophageal reflux. Chronic cough has more than one cause in 20% of patients, so therapy may need to be directed at multiple causes. Gastro-oesophageal reflux may complicate cough from any cause because a cough-reflux feedback cycle can develop. Hence, a four-week trial of an H2-receptor antagonist is indicated in patients with unexplained chronic cough where the history, physical examination, chest x-ray, lung function tests, ear/nose/throat examination and home peak flow monitoring all fail to elucidate a cause. Non-specific therapy should be reserved for when no diagnosis can be made, or when therapy is likely to be ineffective (e.g., lung malignancy).

Adult↗
PubMed1997

Comparison of oral bambuterol and terbutaline in elderly patients with chronic reversible airflow obstruction.

Bambuterol, a carbamate prodrug of terbutaline, is the first once-daily oral beta 2-agonist. The effect/side effect ratio of bambuterol oral solution was compared with terbutaline mixture in elderly patients with chronic reversible obstructive airways disease. The study was of a double-blind, crossover, randomized design and consisted of a 4-7-day run-in period followed by four consecutive treatment periods each of 2 weeks. The treatments were bambuterol solution 20 mg nocte (B20), 10 mg nocte (B10), terbutaline mixture 3 mg t.i.d., (T), and placebo solution (P). Patients measured daily peak expiratory flow rate (PEFR), asthma symptoms, use of inhaled beta 2-agonist, and tremor. Of 84 patients, 66 completed all periods. Mean age was 67 years (60-90), basal FEV1 1.49 L, and reversibility of FEV1 30%. Ninety-four percent of the patients used inhaled/oral steroids in constant dosage. All treatments were significantly more effective than placebo. B20 resulted in higher morning PEFR than T (306 +/- 2.9 L/min vs. 297 +/- 2.9 L/min), while B10 gave equivalent results to T. No differences were seen in the use of inhaled beta 2-agonist. Less shortness of breath was experienced during the night with B20 and during the day with B10 compared with placebo. Both B20 and T produced more tremor than B10 and P. In elderly patients with chronic reversible airways obstruction once-daily bambuterol (10-20 mg) has a better effect/side effect ratio than 3 mg terbutaline thrice daily.

Administration, Oral↗
PubMed1996

Cholelithoptysis: a rare complication of laparoscopic cholecystectomy.

Two months after laparoscopic cholecystectomy, a 54-year-old man presented for medical care with cholelithoptysis (the coughing up of gallstones). This rare complication was managed without a further operation. Possible mechanisms and preventive measures are discussed.

Cholecystectomy, Laparoscopic↗
PubMed1996

Tuberculosis--the threat re-emerges.

Tuberculosis remains a significant problem in Australia with five to six new cases per 100,000 of the population per year. The majority of cases occur in individuals born outside Australia. Approximately 70% is pulmonary disease and 30% nonpulmonary. Diagnosis can be made by history, clinical examination, Mantoux testing, chest X-ray plus a thoracic CT scan and sputum analysis. Occasionally bronchoscopy and/or fine needle aspiration biopsy may be indicated. Six months of appropriate supervised chemotherapy achieves a 98% cure. Healthcare workers are at special risk of infection and should have Mantoux testing; if this is negative then either BCG or regular Mantoux surveillance is recommended. Whilst multi-drug resistant tuberculosis is relatively uncommon in Australia, it is a significant problem in the United States and parts of South East Asia and such patients often come to surgical resection of their tuberculous lesions; during such resection healthcare workers are exposed to a potentially lethal infection.

Antitubercular Agents↗
PubMed1994

Pathogenesis of chronic persistent cough associated with gastroesophageal reflux.

It was previously shown that unexplained chronic cough is associated with asymptomatic gastroesophageal reflux. The aim of this study was to determine if distal esophageal acid is important in the pathogenesis of this cough. In 22 patients with cough and reflux as determined by 24-h ambulatory esophageal pH monitoring, distal esophageal acid perfusion was performed in a double-blind controlled fashion. Patients received both 0.1 N HCl and 0.9% saline for 15 min, in random order. Cough was recorded with a microphone and then computer analyzed. In 12 matched control subjects, 24-h ambulatory esophageal pH monitoring and distal esophageal acid perfusion studies were also performed. In patients, there was a significant increase in cough frequency, median (range): 36.5 (6 to 111) versus 8.3 (0 to 46)/15 min, p < 0.001, and amplitude, geometric mean (range): 85.2 (78.1 to 92.3) versus 73.1 (0.0 to 87.1) dB, p < 0.01, with HCl compared with saline. During HCl infusion, compared with control subjects, patients had more cough episodes, 36.5 (6 to 111) versus 0.0 (0 to 11)/15 min, p < 0.0001, with greater amplitude, 85.2 (78.1 to 92.3) versus 0.0 (0.0 to 79.6) dB, p < 0.001, but there was no difference in cough duration. We subsequently investigated whether inhibition of the induced cough was possible. In seven patients repeat esophageal acid perfusion was performed 15 min after the esophageal instillation of 4 ml of 4% lignocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

New developments in anti-asthma drugs.

OBJECTIVE: To review the current approach to the management of bronchial asthma with particular reference to drug therapy. DATA SOURCES: All significant English language journals were searched for current studies, particularly controlled clinical trials, in the management of asthma. STUDY SELECTION: Sixty articles were reviewed. They were selected on the basis of the known reputation of the author or the unit from which the study emanated, the place that the study has assumed in academic respiratory circles, and whether the study contributed something new to our understanding of drug therapy in asthma. Review articles from eminent scientific bodies were also analysed. CONCLUSIONS: Asthma is an inflammatory disease and therapy must be directed towards this as well as to bronchoconstriction. Inhaled corticosteroids are the mainstay of treatment and inhaled beta-agonists are best used on an as needed basis. Regular objective assessments of patients' progress are essential, as are written, individualised action plans. The adjunctive use of other drugs is discussed and new therapies which may prove useful in the future are reviewed.

Administration, Inhalation↗
PubMed1992

Effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in the well elderly and in patients with chronic bronchitis.

BACKGROUND: Inhalation of the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) produces bronchoconstriction in normal subjects. FMLP thus has a putative role as a mediator of bronchoconstriction associated with bacterial bronchial infection. METHODS: The effects of FMLP inhalation were examined in ten subjects with a history of chronic bronchitis and ten age matched control subjects. Each subject inhaled FMLP doses from 0.025 to 0.8 mumol to determine the provocative dose of FMLP causing a 20% fall in FEV1(PD20FMLP). FEV1 was recorded every five minutes after the final FMLP inhalation until it had returned to 95% of baseline FEV1 or 60 minutes had elapsed. The time to return to 95% baseline FEV1 was recorded or extrapolated from the recovery curve as an index of rapidity of recovery. Total and differential white cell counts were performed on each subject at baseline and five and 15 minutes after the final FMLP inhalation. RESULTS: The geometric mean PD20 FMLP in the patients with chronic bronchitis was 0.06 mumol (95% confidence interval 0.015-0.26), which was significantly lower than that in the control subjects (0.21 mumol (0.02-1.9)). PD20 FMLP in the patients with chronic bronchitis but not age matched controls (p = 0.35) was lower than that found previously in young normal subjects (0.35 mumol (0.07-1.8). The return to 95% baseline FEV1 occurred after 86(10) minutes in subjects with chronic bronchitis and in 81(23) minutes in their age matched controls, in both cases being much slower than that seen in young subjects (29(9) minutes). CONCLUSION: Patients with chronic bronchitis may be especially susceptible to formyl peptides elaborated by bacteria during bacterial bronchial infection.

Administration, Inhalation↗
PubMed1992

Haematological effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in man.

BACKGROUND: N-Formyl-methionyl-leucyl-phenylalanine (FMLP) is a bacterial oligopeptide which stimulates neutrophil chemotaxis, degranulation and superoxide generation. Inhalation of FMLP produces bronchoconstriction in man; in the rabbit this is in part neutrophil dependent. The effects of inhalation of FMLP on peripheral blood leucocytes in normal subjects has been studied. METHODS: This was an open study in non-asthmatic subjects. Change in total peripheral white cell count were studied for 15 minutes after inhalation of 0.4 mumol FMLP in six subjects. Change in total and differential white cell count and spontaneous neutrophil chemiluminescence were then studied five and 30 minutes after inhalation of 0.4 mumol FMLP (n = 7) or diluent (n = 4). Finally, leucocytes from three subjects were labelled ex vivo with technetium-99m labelled sulphur colloid and reinfused. The effect of inhalation of FMLP or diluent on pulmonary neutrophil flux was studied by continuous gamma scanning of a pulmonary window. RESULTS: Leucopenia occurs rapidly after inhalation of FMLP, the nadir of the white cell count (53% of baseline) occurring at four minutes. This was followed by a rebound increase in white cell count evident at 15 minutes (154% of baseline). Five minutes after inhalation of 0.4 mumol FMLP, neutropenia (17% of baseline) and monocytopenia (40% of baseline) were seen followed again by a neutrophilia (213% of baseline at 30 minutes). The eosinophil count was significantly reduced at 30 minutes (24% of baseline). Neutrophil chemiluminescence was elevated (186% of baseline) at the time of the neutropenia. There was no influx of labelled cells to the lung during the period of neutropenia. CONCLUSION: FMLP inhalation activates circulating leucocytes. In vivo production of FMLP in the airway could contribute to bronchial inflammation during bacterial infection.

Administration, Inhalation↗
PubMed1992

Chronic persistent cough and clearance of esophageal acid.

Unexplained chronic persistent cough has been shown to be associated with increased episodes of otherwise asymptomatic gastroesophageal reflux; however, normal subjects without cough also exhibit some reflux. We postulate that the prompt clearance of refluxed acid from the esophagus may play an important role in the prevention of cough, and we sought to determine if patients with chronic cough have impaired clearance. Thirty patients with unexplained chronic cough underwent 24-h ambulatory esophageal pH monitoring. Compared to 12 matched control subjects, patients experienced significantly more episodes (all values expressed as median [range]) of reflux per 24 h (88.3 [5.0 to 338.0] vs 5.7 [0 to 13.0]; p < 0.0001) and had impaired clearance of esophageal acid as measured by the duration of individual reflux episodes (3.0 [0.1 to 20.5] min per reflux vs 0.7 [0 to 2.5] min per reflux; p < 0.01). We conclude that patients with chronic persistent cough have impaired clearance of esophageal acid.

Chronic Disease↗
PubMed1991

Chronic persistent cough and gastro-oesophageal reflux.

Chronic cough persisting for two months or more that remains unexplained after extensive investigations is a common clinical problem. The purpose of this study was to determine whether such cough is associated with otherwise asymptomatic gastro-oesophageal reflux. Thirteen patients with chronic persistent cough that was unexplained after a standard diagnostic assessment were identified. All were non-smokers. The mean (SE) duration of cough was 17.8 (8.0) months. Ten had never had reflux symptoms and three had had mild symptoms only after the onset of the cough. All the patients completed standardised cough diary cards for eight weeks and underwent 24 hour ambulatory oesophageal pH monitoring. A reflux episode was defined as a fall in oesophageal pH to below 4.0. Nine control subjects were matched for age, lung function, and body mass index. The patients experienced significantly more episodes of reflux per 24 hours than the controls (115.8 (SE 31.7) versus 4.7 (1.4) and longer reflux episodes (15.5 (5.8) versus 1.7 (0.5) minutes), and the oesophageal pH was below 4.0 considerably longer (84.5 (20.2) versus 3.8 (1.3) minutes). Cough occurred simultaneously with 13% (2.2%) of reflux episodes and within five minutes in another 35% (5.8%) of episodes, whereas gastro-oesophageal reflux occurred simultaneously with 78% (5.5%) of cough episodes and within five minutes in another 12% (2.3%) of episodes. It is concluded that chronic persistent cough that remains unexplained after a standard diagnostic assessment is associated with otherwise asymptomatic gastro-oesophageal reflux. It is suggested that a self perpetuating mechanism may exist whereby acid reflux causes cough via a local neuronal oesophageal-tracheo-bronchial reflex, and the cough in turn amplifies reflux via increased transdiaphragmatic pressure or by inducing transient lower oesophageal sphincter relaxation. Further study of this mechanism and the role of specific antireflux treatment in chronic persistent cough is warranted.

Adolescent↗
PubMed1991

Effect of neutral endopeptidase inhibition of f-Met-Leu-Phe-induced bronchoconstriction in the rabbit.

Inhalation of f-Met-Leu-Phe (FMLP) produces dose-dependent increases in pulmonary resistance (RL) in rabbits. We hypothesized that inhibition of neutral endopeptidase (NEP), which has high affinity for FMLP, would augment the response to FMLP inhalation. We found the increase in RL above baseline in response to FMLP to be reduced from 56 +/- 18 to 8 +/- 10% (P less than 0.01) by phosphoramidon (1 mg/kg) and to 15 +/- 6% (P less than 0.02) by thiorphan (3 mg/kg). The geometric mean dose of FMLP producing a 20% rise in RL (PC20RL FMLP) was increased by phosphoramidon from 1.1 to 4.5 mg/ml (P less than 0.05). Enkephalins, which are also NEP substrates, modulate cholinergic neurotransmission in the airway. Inhibition of the FMLP response by phosphoramidon was reversed by coadministration of naloxone (0.1 mg/kg); after atropine (2 mg/kg) the change in RL in response to FMLP was reduced to 7 +/- 4% (P less than 0.01), whereas morphine (0.15 mg/kg) increased PC20RL FMLP to 5.1 mg/ml (P less than 0.05). FMLP-induced bronchoconstriction in the rabbit is vagally mediated, and reduced responses after NEP inhibition may reflect modulation of cholinergic bronchoconstriction by enkephalins. Changes in airway NEP activity may influence the activity of a wide range of its substrates, of which some are bronchoconstrictors and others bronchodilators.

Airway Resistance↗
PubMed1991

Effects of prolonged inhalation of N-formyl-methionyl-leucyl-phenylalanine in rabbits.

On the basis of its potent proinflammatory and spasmogenic effects, N-formyl-methionyl-leucyl-phenylalanine (FMLP), a bacterial oligopeptide, is a putative mediator of bronchoconstriction and airway inflammation during bacterial bronchial infection. However, after an FMLP dose-response curve in rabbits, tachyphylaxis to a second challenge was seen in some rabbits and airway inflammation was absent. This study was designed to reproduce the more prolonged airway exposure to FMLP that may occur during bacterial infection. Two groups of rabbits received FMLP [5 mg/ml in 66% dimethyl sulfoxide- (DMSO) saline] or DMSO diluent alone by nebulization every 15 min for 2 h. Pulmonary resistance (RL) was measured at 1 and 2 h. Recovery from bronchoconstriction was also assessed by measuring RL every 30 min for 2 h after the final FMLP administration. Sections of trachea and large bronchi were prepared and graded by quadrant from 0 to 3 for inflammation, a total score from 0 to 12 being given for each section. There was a progressive increase in RL in FMLP-treated rabbits, reaching 68 +/- 9% above baseline after 120 min, a significantly greater change than after diluent, 8 +/- 12% (P less than 0.01). RL remained elevated above baseline for 90 min after the final FMLP dose. Inflammation scores were greater after FMLP than DMSO: 9.3 +/- 0.5 vs. 4.3 +/- 0.7 (P less than 0.01) in trachea and 5.2 +/- 0.4 vs. 1.7 +/- 0.5 (P less than 0.01) in lobar bronchi. We conclude that prolonged exposure of airways to FMLP produces a sustained increase in RL and airway inflammation, the cardinal features of infective exacerbations of chronic airflow limitation.

Administration, Inhalation↗
PubMed1990

Sarcoidosis presenting as recurrent alcohol-induced pancreatitis.

A previously well 27-year-old Caucasian woman presented with five episodes of alcohol-induced abdominal pain over two years culminating in severe acute pancreatitis. Chest x-ray showed bilateral hilar lymphadenopathy and nodular pulmonary infiltrates. In hospital she developed a unilateral facial nerve palsy and other features of sarcoidosis, which was confirmed by biopsy of a pretracheal lymph node. No previous case is reported of sarcoidosis presenting with recurrent pancreatitis apparently induced on each occasion by moderate alcohol consumption and in the absence of other risk factors. Pancreatic involvement as part of sarcoidosis is uncommon but is treatable if recognized and has a good prognosis.

Adult↗
PubMed1989

The effect of anticholinergic and beta-agonist pretreatment on bronchoconstriction induced by N-formyl-methionyl-leucyl-phenylalanine.

N-Formyl-methionyl-leucyl-phenylalanine (FMLP), an acylated tripeptide bacterial neutrophil chemotactic factor, has been shown to be a bronchoconstrictor by inhalation in man in vivo. It thus has a putative role in the generation of bronchoconstriction associated with bacterial bronchial infection. We have investigated the effect of pretreatment with the anticholinergic agent, ipratropium bromide (IB), and the beta 2-agonist, fenoterol (F), on FMLP-induced bronchoconstriction. Ten non-asthmatic subjects aged 21-28 yrs performed dose-response curves to nebulized FMLP on 3 study days after pretreatment with saline, F or IB. Amongst the 8 subjects who bronchoconstricted by 20% to FMLP there was a significant increase in the provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20FMLP) after both IB and F. F was significantly better than IB. When comparison was made using absolute fall in FEV1 and including all 10 subjects the same results were found. Partial inhibition of FMLP-induced bronchoconstriction by IB suggests that part of the effect of FMLP is vagally mediated. We suggest that F is acting via modulation of FMLP-induced rises in intracellular free calcium.

Adult↗
PubMed1987

Long term study of the effect of sodium cromoglycate on non-specific bronchial hyperresponsiveness.

A double blind, crossover study was undertaken to determine whether non-specific hyperresponsiveness in subjects with asthma was reduced by long term treatment with sodium cromoglycate and, if so, whether this was related to change in lung function. Forty four adult asthmatic subjects (41 atopic, three non-atopic) entered the one year study at intervals staggered over six months. After a baseline period to ensure that asthma control was stable subjects entered the treatment period, during which they inhaled sodium cromoglycate 20 mg four times daily or matching placebo four times daily for 16 weeks each, in random order. Response was assessed at four weekly intervals by measurement of lung function and histamine inhalation tests, from which the provocative concentration of histamine causing a 20% fall in FEV1 (PC20H) was calculated. The assessment included daily symptom score, morning and evening Airflow-meter readings and treatment; mean values for each treatment period and also for the final four weeks of each period were compared. There were no significant differences between placebo and sodium cromoglycate treatment for PC20H, FEV1, morning or evening flow meter readings, bronchodilator usage, or symptom scores for the group as a whole, for the 16 week period or for the final four weeks of each period. Thirteen subjects showed better morning and evening flow meter readings while taking sodium cromoglycate than while taking placebo and eight better readings with placebo than with sodium cromoglycate (p less than 0.05). Improvement in lung function did not correlate with baseline lung function or baseline PC20H, or with features of atopy. These results suggest that long term sodium cromoglycate treatment does not alter non-specific bronchial responsiveness in adult asthmatic subjects.

Adolescent↗