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Biomedical subjects

M J Connolly

Publications and source records attributed to M J Connolly.

At least 19 recordsLinked to original sources
PubMed1992

Impaired beta-adrenoceptor function, increased leukocyte respiratory burst, and bronchial hyperresponsiveness.

Inflammatory processes have potential importance in the pathogenesis of bronchial hyperresponsiveness and asthma. Because beta-adrenoceptor function may be impaired in asthma, we studied regulation of the leukocyte respiratory burst using blood samples from subjects with bronchial hyperresponsiveness to methacholine. Leukocytes from hyperresponsive subjects were less responsive to the beta-agonist isoproterenol than were leukocytes from healthy control subjects. The magnitude of the respiratory burst was increased in cells from hyperresponsive subjects and correlated with the degree of methacholine responsiveness. These results demonstrate that peripheral leukocytes reflect a functional impairment in beta-adrenergic responsiveness that parallels airway hyperresponsiveness. Because untreated subjects demonstrated a reduction in beta-adrenergic response, the impairment in beta-adrenoceptor function was not a result of drug therapy and may be associated with the pathogenesis of asthma.

Adult↗
PubMed1992

Clinical significance of crepitations in elderly patients following acute hospital admission: a prospective study.

Because of a clinical impression that lung crepitations are a common, non-specific sign in acutely ill elderly people, two investigators, blinded to each other's findings and to subject case notes, prospectively examined 207 consecutive elderly [aged 70-98 (mean 77) years] and 75 young patients [24-50 (41) years] acutely admitted to hospital. Crepitations and persistent crepitations (PCs) were commoner in the elderly patients (p less than 0.001) but agreement over their presence/absence was reduced (p less than 0.05). Both investigators agreed PCs were absent in 35% of elderly subjects suffering from conditions classically associated with their presence, and, conversely, were present in 29 elderly subjects in whom no cause for their presence was discovered (14% of the total elderly group or 42% of those with PCs). PCs without obvious cause were unrelated to smoking history and did not predict outcome, length of stay or development of cardiorespiratory complications. In view of poor sensitivity and specificity of crepitations in elderly patients undergoing acute hospital admission we caution against over-reliance on this sign in isolation in these circumstances.

Aged↗
PubMed1992

Reduced subjective awareness of bronchoconstriction provoked by methacholine in elderly asthmatic and normal subjects as measured on a simple awareness scale.

BACKGROUND: Asthma death rates are rising, with the greatest rise and highest death rates in old age. A reduced cardiovascular response in the elderly may lead to the underestimation by physicians of the severity of acute asthma attacks. This would be compounded if elderly patients had reduced awareness of bronchoconstriction. METHODS: Methacholine provoked bronchoconstriction was compared in 34 elderly (17 asthmatic, 17 normal; age 60-83, mean 68 years) and 33 young subjects (16 asthmatic, 17 normal; 20-46, mean 30 years). None were smokers. All underwent inhaled methacholine challenge by the Newcastle dosimeter method, monitored by maximal expiratory flow-volume loops (MEFVL). The endpoints were a 35% fall in forced expiratory flow at 50% vital capacity or cumulative inhalation of 6.4 mg methacholine. The one second forced expiratory volume (FEV1) was derived from MEFVL. After challenge and before bronchodilatation subjects graded awareness of respiratory discomfort from 1 (no symptoms) to 4 (pronounced symptoms needing immediate treatment). RESULTS: Despite a greater fall in FEV1 in elderly asthmatic patients (mean (SE) 27.4% (2.2%)) than in young asthmatic patients (21.5% (1.7%)) elderly patients were less aware of bronchoconstriction (awareness score 2.00 (SE 0.15) than young patients (3.06 (0.11)). Similar differences in awareness score were seen between elderly normal subjects (1.53 (0.17)) and young normal subjects (2.76 (0.22)), despite no difference in degree of bronchoconstriction. CONCLUSIONS: Reduced awareness of moderate acute bronchoconstriction in old age may delay self referral in acute asthma and contribute to higher asthma mortality in the elderly.

Adolescent↗
PubMed1992

Relationship between nonspecific bronchial responsiveness to methacholine and peripheral mononuclear leukocyte beta-adrenergic receptor function in young drug-naive subjects.

Asthma is associated with dysfunction of the beta-adrenergic receptor adenylyl cyclase signal transduction pathway. It has been argued that this results from receptor down-regulation by beta-agonist therapy. This study examined the relationship between nonspecific bronchial responsiveness (NSBR) to methacholine (Newcastle dosimeter method) and beta-adrenergic receptor density (Bmax) and affinity (%KH) in membranes from peripheral blood mononuclear leukocytes (MNL) in 12 male (27.3 +/- 1.7 yr old) and 14 female (31.4 +/- 1.7 yr old) drug-naive subjects with and without symptoms of mild intermittent wheezing. None had ever smoked or received any antiasthma medication. "Hyperresponsive" subjects were defined as those (n = 11) whose simplified slope of FEF50 (calculated as the percent fall in FEF50 divided by the dose of methacholine) was more than one SD above the mean for asymptomatic subjects. The log of the slope was reproducible (repeatability coefficient = 0.43) on two nonconsecutive days. Multiple regression analysis (overall R2 = 0.57) revealed negative relationships between the log of the slope and both Bmax (p = 0.016) and %KH (p = 0.011). Analysis of variance confirmed a lower mean (+/- SEM) value of %KH in "hyperresponsives" (45.7 +/- 5.5%) than in "normoresponsives" (60.4 +/- 4.1%, p = 0.04) with a similar trend for Bmax (hyperresponsives = 33.5 +/- 4.1 fmol/mg, normoresponsives = 45.9 +/- 7.1 fmol/mg, p = 0.18). These relationships between bronchial responsiveness, Bmax, and %KH cannot be explained by drug therapy, and they provide further evidence that there is an intrinsic impairment in the function of beta-adrenergic receptors on peripheral MNLs from subjects with high levels of nonspecific bronchial responsiveness.

Adolescent↗
PubMed1991

Torsades de pointes ventricular tachycardia and terodiline.

We report five patients (four women, one man; mean age 74 years, range 55-87) taking terodiline who had torsades de pointes ventricular tachycardia associated with prolongation of the QT interval. The QT interval was normal before the introduction of terodiline in three patients and returned to normal after terodiline withdrawal in four. Atrioventricular conduction disturbance or bradycardia were evident in all patients. Terodiline should be prescribed with caution to elderly patients.

Aged↗
PubMed1990

Kitchen aids.

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Aged↗
PubMed1990

The mass spectra of 4-aminophenanthrene and its trifluoroacetic anhydride and perfluoropropionic anhydride derivatives.

Several aminophenanthrenes have been examined with electron impact mass spectrometry. The trifluoroacetic anhydride (TFAA) and perfluoropropionic anhydride (PFPA) derivatives of 4-aminophenanthrene have been studied with electron impact as well as both positive and negative ion chemical ionization mass spectrometry utilizing methane as a reagent gas. The resulting mass spectra indicate a loss of water from the derivatives and a mechanism is proposed to account for this loss. The spectra also indicate unique fragmentation patterns associated with the position of the substituent, particularly the four position which is in the region of the molecule termed the bay region. Another interesting aspect is the spectral differences observed for the TFAA and PFPA derivatives of 4-aminophenanthrene. The positive ion chemical ionization mass spectrum of the TFAA derivative indicates an ion [M + H - H2O]+; however, the mass spectrum of the PFPA derivative of 4-aminophenanthrene indicates no water loss from the [M + H]+ ion. The negative ion chemical ionization mass spectra of the two derivatives are also very different. The mass spectrum of the TFAA derivative shows an [M - 18]- ion and the PFPA derivative shows successive losses of HF with no apparent loss of water.

Mass Spectrometry↗
PubMed1989

Hypercalcaemia in association with enteric fever.

We report 2 cases of hypercalcaemia and hypercalciuria, with detectable levels of parathyroid hormone, which appeared to be precipitated by enteric fever. Extensive investigation of one case, including ultrasound, isotope scanning, angiography, computed tomographic scanning and surgical exploration, failed to detect a parathyroid adenoma. In both cases biochemical and hormonal abnormalities resolved several months after recovery of enteric fever. The mechanism of the proposed association is unexplained but it should be considered in any patient with hypercalcaemia and detectable parathyroid hormone levels, who is suffering from or has recently recovered from enteric fever. If such a patient is well, a period of several month's observation is recommended. We believe these two cases to be the first such reports of hypercalcaemia in association with enteric fever.

Adolescent↗
PubMed1989

Refractory period following bronchoconstriction provoked by histamine in asthmatic subjects.

To determine whether refractoriness to histamine induced bronchoconstriction occurs, 20 asthmatic subjects aged 19-50 years were tested. Subjects underwent two histamine challenge tests (1 and 2) on the same day, the second one being given 45-60 minutes after the first, once the FEV1 after test 1 had returned spontaneously to within 90% of baseline. A further "control" histamine challenge test was carried out on a different day at the same time (+/- 2 hours) as test 1. Bronchial responsiveness was recorded as the cumulative dose (microgram) of histamine provoking a 20% fall in FEV1 (PD20), and the ratio PD20 test 2:PD20 test 1 was used to assess refractoriness. The median value of this ratio (2.20) was significantly greater than 1 (p = 0.003), indicating refractoriness at the time of test 2. By contrast the median ratio PD20 control:PD20 test 1 of 1.03 was not significantly different from 1. Refractoriness could not be accounted for by failure to regain the initial baseline FEV1, though such failure may have exaggerated the effect. An increase in PD20 with the second test was observed uniformly in subjects with moderate or high initial PD20 values but not in those with low values. This suggests that there may be a PD20 threshold of the order 25-100 micrograms for refractoriness to occur. Refractoriness could exert an important confounding effect in investigations in which repeated histamine tests are carried out at short intervals.

Adult↗
PubMed1988

The use of sequential doses of inhaled histamine in the measurement of bronchial responsiveness: cumulative effect and distortion produced by shortening the test protocol.

We have evaluated a shortened protocol for measuring bronchial responsiveness to histamine. This safely eliminates unnecessarily low doses from a standard doubling dose sequence (i.e., full protocol) so that the dose provoking the definitive 20% decrement in FEV1 (PD20) is usually reached within two or three dose increments. In 20 subjects with asthma tested with both protocols, the ratio of geometric mean PD20 short protocol (86.8 micrograms) to PD20 full protocol (45.7 micrograms) was significantly greater than 1 when the results were expressed on a noncumulative scale (1.90 versus 1; p less than 0.001). When PD20 was expressed on a cumulative scale, the discordance was less striking (123.7 versus 89.2 micrograms, respectively), but this ratio (1.39) was still significantly greater than 1 (p = 0.007). By contrast, duplicated measurements of PD20 with the full protocol and the cumulative scale elicited a ratio of geometric mean PD20 day 1 (63.0 micrograms) to PD20 day 2 (67.0 micrograms) of 0.94, which was not significantly different from 1. Thus, the bronchoconstrictor effect of histamine depends on both the cumulative dose and the number of component doses. We conclude (1) that PD20 histamine is more nearly accurately expressed on a cumulative than on a noncumulative scale and (2) that histamine is less suitable for shortened protocols than methacholine because a reduction in the number of component doses produces significant distortion of the PD20 result.

Administration, Inhalation↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1987

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↗