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Biomedical subjects

K S Higgins

Publications and source records attributed to K S Higgins.

11 recordsLinked to original sources
PubMed1996

No relation between angiotensin-converting enzyme gene polymorphism and dermal response to bradykinin in healthy subjects.

1. The dermal wheal response to bradykinin is increased by drugs which inhibit angiotensin-converting enzyme, and thus provides a measure of angiotensin-converting enzyme activity at the tissue level. An insertion/deletion polymorphism of the angiotensin-converting enzyme gene predicts serum angiotensin-converting enzyme activity, but its relation to angiotensin-converting enzyme activity in tissue is unclear. 2. The relations between angiotensin-converting enzyme genotype and wheal responses to intradermal bradykinin were studied in 105 healthy subjects: 30 of genotype DD, 51 of genotype ID and 24 of genotype II. Dermal wheal area was measured by digitized planimetry and the angiotensin-converting enzyme genotype by polymerase chain reaction. 3. Bradykinin produced significant linear log dose-wheal area responses. The potency of bradykinin by parallel line bioassay did not differ significantly between the genotypes; the potency in the II subjects relative to DD subjects was 1.25 (95% confidence interval: 0.83-1.88). 4. Although the angiotensin-converting enzyme gene polymorphism is a consistent and powerful predictor of serum angiotensin-converting enzyme activity, it does not appear to predict tissue angiotensin-converting enzyme activity as measured by dermal responses to bradykinin.

Adult↗
PubMed1995

Relation between changes in blood pressure and serum ACE activity after a single dose of enalapril and ACE genotype in healthy subjects.

1. The effects of a single oral dose of enalapril 10 mg on serum ACE activity and blood pressure in relation to the ACE genotype were studied in 27 healthy men, n = 9 each of genotype DD, ID and II, in a parallel group study design. 2. Before treatment serum ACE activity differed significantly between the genotypes, with serum ACE activity 56% higher in DD than II subjects, and the genotype explaining 40% of between-subject variance in serum ACE activity. 3. After oral enalapril 10 mg the absolute fall in serum ACE activity was significantly larger in DD than II subjects at 2, 4, and 6 h (by 9.0 (95% CI 0.7-17.2), 10.7 (3.8-17.6), and 9.7 (2.8-16.6) nmol ml-1 min-1 respectively), but not at 24 h (fall in II > DD by 1.1 (-8.9 to 6.7) nmol ml-1 min-1). 4. Serum ACE activity remained significantly related to the ACE genotype at each time-point after enalapril, with the genotype explaining 22-46% of between-subject variance in serum ACE. 5. Falls in mean arterial pressure in response to enalapril were not significantly related to the ACE genotype, with the average fall over 6 h in DD > II genotype by 0.7 mm Hg (95% CI -5.5 to 4.1). 6. Blood pressure responses to enalapril did not correlate significantly with the initial serum ACE, or the absolute or percent reductions in serum ACE activity after enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The effect of inhaled and oral dextromethorphan on citric acid induced cough in man.

1. Dextromethorphan is a widely used antitussive agent which is a non-narcotic codeine analogue. We have investigated whether inhaled administration of dextromethorphan provides antitussive activity in a citric acid induced cough model. 2. Twenty normal subjects underwent repeated cough challenge with 5% citric acid. Subjects were studied on six occasions. Study medication consisted of oral dextromethorphan 30 mg or oral matched placebo or 1, 3 and 30 mg inhaled dextromethorphan or matched inhaled placebo. Cough challenge was administered 10 min after study medication and hourly thereafter up to 250 min. 3. No significant differences were seen between baseline cough responses. Oral dextromethorphan (30 mg) produced a mean percentage reduction in cough of 38% (P < 0.002), which remained significant at 250 min. Inhaled dextromethorphan had no clinically significant effect although activity at later time points was not excluded. The antitussive effect of oral dextromethorphan is confirmed with prolonged inhibition of induced cough. It is possible that dextromethorphan or its active metabolites act centrally to inhibit the cough reflex.

Administration, Inhalation↗
PubMed1995

Effect of dose adjustment on enalapril-induced cough and the response to inhaled capsaicin.

1. In nine hypertensive patients with enalapril-induced cough the effect of altering the dose of enalapril on subjective cough and the cough response to inhaled capsaicin was examined in a random single-blind balanced cross-over study. They received three doses of enalapril, each for 3 weeks; the dose at entry (mean 10 mg daily); double this dose (mean 20 mg daily); and half this dose (mean 5 mg daily). 2. The cough response to inhaled capsaicin was also measured in two control groups: hypertensive patients on long-term enalapril treatment with no cough (n = 18), and hypertensive patients taking nifedipine (n = 17). 3. In patients with enalapril-induced cough there were significant dose-responses for enalapril as regards severity of cough (P < 0.05) and night time waking by cough (P < 0.05), but not for frequency of cough. Although the cough was less severe (P < 0.02) and caused less night time waking (P < 0.03) on the lowest dose of enalapril (mean 5 mg daily) it did not disappear completely in any patient. 4. The sensitivity to inhaled capsaicin did not differ significantly on the three doses of enalapril. The relative potency of capsaicin on enalapril 20 mg compared with enalapril 5 mg was 1.0 (95% CI 0.4-2.2). The wide confidence limits indicate that an important dose-dependent shift in capsaicin sensitivity is not excluded. 5. The sensitivity to inhaled capsaicin differed significantly between patients with enalapril-induced cough and both control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

Effect of inhaled menthol on citric acid induced cough in normal subjects.

BACKGROUND: Menthol is a commonly used ingredient in many over the counter cough remedies, but there is little objective evidence as to its efficacy. METHODS: Twenty healthy subjects received a cough challenge consisting of five inhalations of 33 mumol citric acid from an air driven dosimeter. The challenge was repeated at hourly intervals for five hours. Five minutes before each challenge subjects inhaled, in a randomised design, either menthol 75% in eucalyptus oil or one of two placebos (pine oil or air). RESULTS: Menthol inhalation caused a reduction in evoked cough when compared with either placebo. CONCLUSIONS: Menthol is an effective antitussive agent in an evoked cough model.

Administration, Inhalation↗
PubMed1993

A comparative study of the effects of citric acid, capsaicin and resiniferatoxin on the cough challenge in guinea-pig and man.

The cough response following inhalation challenge with the sensory nerve irritant resiniferatoxin was compared with that of capsaicin and citric acid in guinea-pig and man. Capsaicin and citric acid gave comparable dose-response curves in the two species. The mean (+/- SEM) concentration producing five coughs in man was 141.3 (1.3) mM (n = 10) for citric acid and 2.8 (1.3) microM (n = 10) for capsaicin. Those for the guinea-pig were 74.1 (1.2) mM (n = 10) for citric acid and 6.0 (2.4) microM (n = 10) for capsaicin. Resiniferatoxin was active at a lower concentration than either citric acid or capsaicin and maximal tolerable cough response was achieved at concentrations of 3 microM (n = 5) in guinea-pig and 300 nM (n = 1) in man. The cough response to resiniferatoxin was greatly prolonged in both guinea-pig and man. Resiniferatoxin, like capsaicin, caused respiratory distress in the guinea-pig which is linked to bronchoconstriction. Resiniferatoxin probably causes cough by stimulation of capsaicin sensitive neurones.

Administration, Inhalation↗
PubMed1992

Adaptation of cough reflex with different types of stimulation.

Inhalation cough challenge has become an accepted method of investigating antitussive agents. It is, therefore, important to examine the degree of tachyphylaxis seen with repeated cough challenge. In addition, different types of challenge may reveal important differences in the neuronal pathways involved in the cough reflex. Citric acid, distilled water and capsaicin were examined to determine adaptation of the cough response during acute and long-term inhalation studies in healthy subjects. To study acute tachyphylaxis two separate one minute continuous inhalation challenges (n = 13) were performed. Long-term tachyphylaxis (n = 10) was examined using citric acid and capsaicin inhalation at 10 min intervals for 40 min, and at 4 and 6 h. Cross-tachyphylaxis to citric acid and capsaicin was examined in a separate randomized crossover study (n = 10). Highly significant adaptation occurred between the first and last 10 s of the one minute challenge with citric acid (90-100%) and distilled water (74-84%), but was less pronounced with capsaicin (37-49%, at 2 microM). Cough during the whole of the second test was significantly reduced for citric acid (50%). During long-term challenge cough was attenuated over 40 min both with citric acid (100 mM, p less than 0.05; 300 mM, p less than 0.001; 1 M, p less than 0.001) and with capsaicin (3 microM, p less than 0.01; 10, 30, 100 microM, p less than 0.001 each). With higher doses, tachyphylaxis was still present at 180 min with both citric acid (300 mM, p less than 0.05) and capsaicin (100 microM, p less than 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗