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M J Connolly

Publications and source records attributed to M J Connolly.

65 records · Page 4Linked to original sources

The relationship between bronchial responsiveness to methacholine and bronchial responsiveness to histamine in asthmatic subjects.

There is widespread belief that methacholine responsiveness in asthmatic subjects is closely related to histamine responsiveness, and that the two agents may be used interchangeably in the measurement of non-specific bronchial responsiveness (NSBR). Because this view has been challenged, we have examined the repeatability of measurements of bronchial responsiveness to methacholine and histamine and the relationship between them, in groups of 20 adult asthmatic subjects. Bronchial responsiveness was expressed as the cumulative dose (in both micrograms and mmols) provoking a 20% fall in FEV1 (PD20). The predicted 95% confidence limits for the second PD20 measurement of a further pair were within the range 0.5-2.0 x first PD20 for both agents. When the two agonists were compared in the same subjects, a significant difference in potency was noted (ratio of geometric means PD20.methacholine to PD20.histamine 2.19 [micrograms], 3.43 [mmols]; p = 0.0003). Furthermore, the variance of the differences of the pairs of log PD20.methacholine and PD20.histamine measurements was found to be significantly greater than that of either the paired methacholine measurements or the paired histamine measurements (p less than 0.01). We conclude firstly that methacholine is a less potent bronchoconstrictor than histamine and secondly that, while inhalation tests with either agent broadly reflect the degree of NSBR, they measure different phenomena and cannot be used interchangeably even after allowance is made for the difference in potency.

Adult↗

An assessment of methacholine inhalation tests in elderly asthmatics.

We have assessed the feasibility and value of measuring nonspecific bronchial responsiveness to methacholine in investigation of asthma in the elderly. Results from duplicated tests in 20 subjects aged 65-82 years were expressed as dose provoking a 20% decrement in 1 second forced expiratory volume (PD20.FEV1) or peak expiratory flow (PD20.PEF). Repeatability for PD20.FEV1 was satisfactory but less good than in younger subjects, 95% confidence limits being 0.39-2.57 and 0.52-1.91, respectively, x initial PD20. For PD20.PEF, confidence limits were wider (0.26-3.91 x initial PD20) but multiple PEF measurements were better tolerated than those of FEV1, which commonly caused fatigue and dizziness. PD20.FEV1 and PD20.PEF correlated closely (r = 0.95, P less than 0.0001) and both predicted bronchodilatation following a 6-week course of inhaled corticosteroid and beta agonist. This was not predicted by the response to a single dose of beta agonist. We conclude that measurement of bronchial responsiveness is feasible and clinically valuable in elderly subjects.

Aged↗

Occupational asthma due to sodium iso-nonanoyl oxybenzene sulphonate, a newly developed detergent ingredient.

Research with sodium iso-nonanoyl oxybenzene sulphonate (SINOS) for use in a detergent product was complicated by the development of asthma in an atopic 38 year old laboratory technician. Inhalation challenge tests with nebulised SINOS solutions over a dose range of 0.01-32 micrograms gave reproducible late asthmatic reactions after the higher doses and an increase in bronchial responsiveness to methacholine. The magnitude of the late reaction was related to the challenge dose.

Adult↗

Plasma beta-endorphin levels in silent myocardial ischemia induced by exercise.

Although silent myocardial ischemia is a well recognized phenomenon, the reasons for the lack of symptoms in patients with coronary artery disease (CAD) is unclear. Because the endogenous opioid beta-endorphin has been related to pain modulation, plasma beta-endorphin levels were studied before, during and after exercise-induced ischemia in symptomatic and asymptomatic men. Because beta-endorphin responses have been closely linked to adrenocorticotropic hormone (ACTH) and cortisol responses, these hormones also were measured. Nine symptomatic and 12 asymptomatic patients with a high probability (at least 95%) of CAD and 8 apparently healthy men completed a Bruce protocol treadmill test. Blood samples were drawn before, during and 10 minutes after exercise. During exercise the measured hormones showed no significant increases from basal levels. However, plasma beta-endorphin, ACTH and cortisol levels were significantly elevated (p less than or equal to 0.01) 10 minutes after exercise in all 3 groups. There was no significant difference in plasma beta-endorphin levels during or after exercise between the symptomatic and asymptomatic patients with CAD. Thus, differences in circulating levels of beta-endorphin, ACTH and cortisol are not associated with the presence or absence of pain during exercise-induced myocardial ischemia.

Adrenocorticotropic Hormone↗

Modification of the methacholine inhalation test and its epidemiologic use in polyurethane workers.

The dosimeter method of administering doubling cumulative doses of methacholine to measure bronchial responsiveness was standardized to control for the effects of a number of potential influencing variables. The aerodynamic mass median diameter of the challenge aerosol produced from a DeVilbiss 646 nebulizer proved to be 1.2 mu, and the mean output per inhalation 8.9 microliters. Each challenge dose comprised 5 inhalations. Cumulative doses ranged from 0.3 methacholine inhalation units (1 unit = 1 inhalation of aerosol from a 1-mg/ml solution of methacholine, i.e., 8.9 micrograms methacholine) to a possible 640 units, the maximum that was considered reasonable to avoid the risk of unacceptable systemic effects. Responsiveness was expressed as the dose provoking a 20% decline (PD20) in FEV1. Modifications in this full protocol were introduced to facilitate epidemiologic investigations. Physician assessments coupled with baseline measurements of ventilatory function allowed starting at higher dosages for persons with low probability of hyperresponsiveness, thereby shortening the time required for testing to an average of 38 min. In a validation study of 20 persons using both the full and modified protocols, no significant differences were detected between measured PD20 values (geometric means Full versus Modified, 14.83 versus 14.88; r = 0.99). The modified protocol was used to measure bronchial responsiveness in 254 workers exposed to toluene diisocyanate. It proved to be safe and acceptable. Sixty-four workers (25.2%) were found to be reactors. The frequency distribution of the PD20 values exhibited a steadily increasing trend, consistent with a unimodal distribution.

Adult↗

Mycobacterium malmoense in the north-east of England.

We report a 6 year experience (1979-1984) of isolating Mycobacterium malmoense in the north-east of England. Eleven subjects were involved of whom 10 had active infection--9 pulmonary, one cervical adenitis. The 11 new isolates represent 0.7% of all new mycobacterial isolates during this period and 10% of new non-tuberculous isolates. In all but 2 cases there was pre-existing pulmonary disease and/or a recognised predisposing factor to mycobacterial infection. The organisms were generally insensitive to isoniazid but sensitive to both rifampicin and ethionamide. The results of chemotherapy are described.

Adult↗

Occupational asthma. Update on a proliferating problem.

The list of agents known or suspected to cause occupational asthma is increasing almost daily. Potency, dose, and size of the population exposed determine the magnitude of the problem in any given industry. Investigation involves determining whether asthma is present, whether it is occupational, and what agent is responsible. Management of occupational asthma must be approached on an individual basis and at an industry-wide level.

Asthma↗

Familial, EsD-linked, retinoblastoma with reduced penetrance and variable expressivity.

We report an example of four generation familial retinoblastoma in which there are three distinct categories of RB gene expression: frank retinoblastoma, unilateral or bilateral; retinoma; and no visible evidence of retinal pathology other than normal degeneration with age. Two large sibships derived from matings informative for RB and EsD provide strong confirmatory evidence for tight linkage between these loci (P = 0.0002), and thus assignment of RB to chromosome 13q14. There is a striking difference (P less than 2%) in RB penetrance between the two principal generations, which suggests that an additional epistatic, host-resistance gene may also be segregating within the family.

Adult↗

Feeding aids.

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Aged↗