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Biomedical subjects

S W Clarke

Publications and source records attributed to S W Clarke.

At least 19 recordsLinked to original sources
PubMed1992

Transient positive and negative experiences accompanying stage hypnosis.

Frequency of positive and negative experiences accompanying stage hypnosis was assessed in follow-up interviews with 22 participants of university-sponsored performances. Most subjects described their experience positively (relaxing, interesting, exciting, satisfying, illuminating, and pleasurable), but some described it negatively (confusing, silly, annoying, and frightening). Five subjects (22.7%) reported partial or complete amnesia; all were highly responsive to the stage hypnosis suggestions. One subject was completely unable to breach amnesia and felt annoyed and frightened. Five subjects (22.7%) believed the hypnotist had control over their behavior. Participants (n = 15) tested subsequently on the Stanford Hypnotic Susceptibility Scale, Form C (Weitzenhoffer & Hilgard, 1962) were mostly moderately to highly hypnotizable (M = 7.07), and the scores correlated significantly (r = .68) with the percentage of passed stage hypnosis suggestions.

Adolescent↗
PubMed1992

Acute effect of inhaled bradykinin on tracheobronchial clearance in normal humans.

BACKGROUND: Bradykinin, a nonapeptide that contributes as a mediator to the pathogenesis of asthma, may affect lung mucociliary clearance, as it has been shown to be a potent secretagogue in canine airways and in human nasal mucosa in vivo. To evaluate this possibility the effect of inhaled bradykinin on mucociliary clearance has been studied in 10 healthy volunteers. METHODS: Subjects attended the laboratory on two occasions to take part in tracheobronchial clearance studies using a non-invasive radioisotopic technique. Inhalation of radioaerosol was followed 30 minutes later by inhalation of either bradykinin (8 mg/ml) or vehicle placebo in a randomised, double blind fashion. After each inhalation the number of coughs was recorded. Whole lung radioactivity was measured every half hour for six hours with two collimated scintillation counters, and a tracheobronchial clearance curve was plotted for each subject on each occasion. RESULTS: Mucociliary clearance, expressed as the area under the tracheobronchial radioaerosol retention curve calculated for the first six hours (AUC0-6h), was greater in nine out of 10 subjects after inhalation of bradykinin than after placebo. The median values (range) for AUC0-6h were significantly reduced from 126% (78-232%)/h with placebo to 87% (51-133%)/h with bradykinin. CONCLUSION: It is concluded that acute exposure to inhaled bradykinin accelerates tracheobronchial clearance in normal human airways.

Administration, Inhalation↗
PubMed1992

Effect of temazepam on tracheobronchial mucus clearance.

BACKGROUND: Tracheobronchial clearance of mucus from the lungs is reduced during sleep and, usually, by the administration of opiates. It seemed possible therefore that temazepam, a widely used potent benzodiazepine, retarded clearance. METHODS: The effect of 10 mg temazepam on mucociliary clearance was studied in eight healthy volunteers, aged 18-50 (mean 30) years, in a randomised, placebo controlled, double blind, cross-over study. Six subjects were female and two male. Six were non-smokers and two were light current smokers. Clearance was assessed from the change in radio-activity in the lungs after inhalation of 5 microns diameter polystyrene particles, labelled with technetium-99m, under controlled conditions. RESULTS: Tracheobronchial clearance was reduced by 22% after temazepam by comparison with placebo during the first three hours after drug ingestion; this is the period when circulating drug concentrations are highest. CONCLUSION: Temazepam should be prescribed with caution in patients with impaired lung mucociliary transport.

Adolescent↗
PubMed1992

Tracheobronchial clearance in patients with pulmonary sarcoidosis.

Lung mucociliary clearance was measured using an objective, noninvasive radioaerosol technique in 13 patients with pulmonary sarcoidosis and 13 matched, healthy control subjects. Four of the sarcoid patients had never received any steroid therapy, five were currently receiving oral corticosteroids, and the remaining four were using inhaled corticosteroids only. A statistically significant retardation in tracheobronchial clearance (p less than 0.02) was observed in the sarcoid patients compared to the control subjects. The sarcoid patients using inhaled corticosteroids appeared to demonstrate the greatest degree of mucociliary transport impairment. The sarcoid patients in apparent remission and those receiving oral corticosteroid therapy had clearances better than those using inhaled corticosteroids, but they were still reduced compared to the control subjects. This study demonstrates that lung mucociliary clearance is adversely affected in patients with pulmonary sarcoidosis and raises the question of the possible consequences that could follow long-term inhaled immunosuppressive therapy on the prime clearance defense mechanism within the human lungs.

Adrenal Cortex Hormones↗
PubMed1992

Alveolar macrophages that suppress T-cell responses may be crucial to the pathogenetic outcome of pulmonary sarcoidosis.

The alveolar macrophage (AM) population is widely recognized to be heterogeneous; distinct subpopulations can be identified by the use of macrophage-specific monoclonal antibody (MoAb) probes. We have isolated a macrophage subset that appears to react with both MoAbs that have previously discriminated between dendritic cells and classic macrophages. In the bronchoalveolar lavage (BAL) of patients with active sarcoidosis the proportion of this specific AM subpopulation increases dramatically (30.4 +/- 4.01% compared to 6.14 +/- 1.56% in normal BAL). This AM subset not only increases in direct proportion to the lavage lymphocytosis, but also exhibits sarcoid-related differences in surface receptor expression, physiology and induction of T-cell responses. An increased number of these AM expressed a separate antigen RFD9 (which identified epithelioid cells), and had raised fibronectin content, increased phagocytosis, and high lysosomal enzyme activity. Of functional significance, we found that while in normal volunteers this specific AM subset was capable of down-regulating by as much as 40% the induction of T-cell responses set up by other stimulator macrophages, in sarcoid patients this suppressor activity was enhanced, such that T-cell responses were completely abolished. In some studies this action was masked by the reduced enhancing capacity of sarcoid inducer AM. We postulate that the presence of an increased proportion of these suppressor AM (together with their sarcoid-specific features) in active sarcoidosis is of crucial significance in determining the fate of granulomata in the lungs of these patients.

Adult↗
PubMed1992

Isolation of phenotypically and functionally distinct macrophage subpopulations from human bronchoalveolar lavage.

Bronchoalveolar lavage was used to obtain alveolar macrophages (AM) from the lower respiratory tract of healthy normal volunteers. Monoclonal antibody (MoAb) probes specific against macrophage determinants were then applied, in conjunction with density separation techniques, to identify and isolate three relatively homogeneous subpopulations from the AM pool. The MoAbs used, RFD1 and RFD7, have previously been shown to differentiate between "dendritic" cells and mature macrophages, respectively, in normal tissue. In addition to these two phenotypically distinct AM subsets (RFD1+D7- and RFD1-D7+ AM), a third AM subpopulation was isolated, which appeared to express both markers (RFD1+D7+). All three separated macrophage subsets were morphologically similar but exhibited distinct differences in surface receptor expression, enzyme content and physiology. Isolated RFD1+D7- AM (the phenotype of "dendritic" cells) did not adhere to the glass, had weak expression of C3b and FcR1 receptors, low fibronectin content and lysosomal activity; only a small proportion of these cells exhibited phagocytosis. The other two isolated AM subsets adhered to glass, expressed C3b and FcR1 receptors, had high fibronectin and acid phosphatase content, and a large majority exhibited phagocytic capacity; qualitative and quantitative differences in these features existed between the two AM subtypes. Furthermore, a diverse spectrum of hexose monophosphate shunt activity was observed throughout all three AM subpopulations, with the highest activity being recorded in the non-adherent AM. These data support the concept of a dynamic heterogeneity within the AM population. The variation in surface antigen expression and physiological capabilities observed amongst the three isolated AM subsets implies the presence of functionally distinct AM within the human lung, which, during steady-state conditions, may be critically balanced under the influence of stimuli in their local microenvironment. In support, proportional and functional shifts have been witnessed amongst these three AM subpopulations with the advent of disease.

Adult↗
PubMed1991

The effect of unproductive coughing/FET on regional mucus movement in the human lungs.

The study was designed to ascertain the movement of mucus from proximal and peripheral regions within the human lungs during cough and the forced expiration technique (FET). Mucus movement was measured using a radioaerosol technique. Seven patients (mean +/- SEM age: 63 +/- 3 years) with airways obstruction (% predicted FEV1: 44 +/- 4) participated in the study. Each patient underwent three assessments in a randomized manner: control/cough/FET. Peak expiratory flow rate (PEFR) was measured at the mouth during cough and FET. None of the patients produced sputum during the assessment periods. Both cough and FET compared with control increased, on average, mucus clearance from all regions; statistical significance was achieved only for central lung regions with cough (P less than 0.05). There was no significant correlation between PEFR during cough/FET and regional lung clearance.

Aerosols↗
PubMed1991

Improvement of drug delivery with a breath actuated pressurised aerosol for patients with poor inhaler technique.

BACKGROUND The metered dose inhaler is difficult to use correctly, synchronising actuation with inhalation being the most important problem. A breath actuated pressurised inhaler, designed to help patients with poor inhaler technique, was compared with a conventional metered dose inhaler in terms of aerosol deposition and bronchodilator response. METHODS Radioaerosol deposition and bronchodilator response to 100 micrograms salbutamol were measured in 18 asthmatic patients, who inhaled from a conventional metered dose inhaler by their own chosen metered dose inhaler technique, from a conventional metered dose inhaler by a taught metered dose inhaler technique, and from a breath actuated pressured inhaler (Autohaler). RESULTS In the 10 patients who could coordinate actuation and inhalation of the inhaler on their own deposition of aerosol in the lungs and bronchodilator response were equivalent on the three study days. By contrast, in the eight patients who could not coordinate the mean (SEM) percentage of the dose deposited in the lungs with their own inhaler technique (7.2% (3.4%] was substantial lower than those attained by the taught metered dose inhaler technique (22.8% (2.5%] and by Autohaler (20.8% (1.7%]. CONCLUSION Although of little additional benefit to asthmatic patients with good coordination, the Autohaler is potentially a valuable aid to those with poor coordination, and should be considered in preference to a conventional metered dose inhaler in any patient whose inhaler technique is not known to be satisfactory.

Administration, Inhalation↗
PubMed1991

Effect of inhaled 15-(s)-hydroxyeicosatetraenoic acid on tracheobronchial clearance in normal human airways.

15-(s)-Hydroxyeicosatetraenoic acid (15-HETE) is the predominant metabolite of arachidonic acid in normal and asthmatic human airways and a potent mucus secretagogue in canine and human airways. A study was carried out on the effect of inhaled 15-HETE on tracheobronchial clearance, measured for six hours by a radioaerosol technique, in 10 normal subjects. Subjects inhaled 80 nmol 15-HETE or the diluent (sodium phosphate buffer) on two occasions at least two weeks apart in a double blind and randomised fashion (20 minutes after radioaerosol inhalation. Tracheobronchial clearance after inhaled 15-HETE was almost identical to that after placebo for all measurements up to six hours. It is concluded that 15-HETE has no effect on tracheobronchial clearance in normal human airways and is unlikely to account for the impaired mucociliary clearance seen in asthma.

Administration, Inhalation↗
PubMed1991

Chronic bronchitis in the 1990s: up-to-date treatment.

Prevention is the key to eradicating chronic bronchitis. Smoking is the prime factor involved. Quitting smoking is difficult even with modern aids such as counselling, filters, substitutes, hypnosis and acupuncture, and the success rate is only 20%. Passive smoking is also injurious. The role of atmospheric pollution is less well quantified. Other risk factors include lower social class, occupation, area of residence, housing, temperature, and childhood respiratory illness. Influenza vaccination gives 60-70% immunity. With exacerbations of chronic bronchitis, beta-lactamase-producing bacteria are important, though the overall need for antibiotics is uncertain judging by placebo-controlled studies. Inhaled beta 2-agonist bronchodilators may improve airflow obstruction, as may anticholinergic drugs (e.g. ipratropium), the two being additive. Oral theophyllines have a narrow therapeutic window, serious side-effects and only two thirds of the effect of beta 2-agonists. A corticosteroid trial for 2 weeks may relieve refractory airway obstruction in 17-23% of chronic bronchitis, to be followed by inhaled steroids. Mucolytic drugs remain controversial and are difficult to monitor successfully. Oxygen therapy may be indicated for hypoxic chronic bronchitis, including long-term usage in cor pulmonale. Pulmonary rehabilitation by exercise training has recently been appreciated, and may be used in combination with the above treatment modalities.

Adrenal Cortex Hormones↗
PubMed1991

Beer versus mixed-drink consumption at fraternity parties: a time and place for low-alcohol alternatives.

Blood alcohol concentration (BAC) measurements were taken of university students entering and exiting three fraternity parties: during each party, the rates of drinking beer and mixed drinks were monitored. The parties choose beer or mixed drinks to consume exclusively throughout the evening at no cost. Unbeknownst to the subjects, the following conditions were manipulated across successive parties: (1) at the first party (64 males and 43 females) the beer alternative had standard alcohol content (i.e., 7% alcohol by volume), (2) at the second party (70 males and 48 females) the beer was a low-alcohol beer (3% alcohol) and (3) at the third party (53 males and 41 females) the partiers were randomly assigned to a regular alcohol content conditions of beer or mixed drinks or to a low-alcohol content condition (i.e., 3% beer or mixed drinks made with 7/8-oz of distilled spirits). Since those assigned to the low-alcohol conditions did not consume more beverages than those in the regular alcohol conditions, a titration hypothesis was not supported and the exit BACs were significantly lower for partiers in the low-alcohol conditions. When females drank at the same rate as males, their exit BACs were significantly higher than those of males. Implications for DWI prevention are discussed.

Accidents, Traffic↗
PubMed1991

Knowing when to say when: a simple assessment of alcohol impairment.

The use of writing samples as indices of alcohol impairment was explored. Students at a campus fraternity party wrote a sentence and their signatures before and after consuming alcohol (in beer and mixed drinks). Later, undergraduate and graduate students attempted to discriminate between pre- and postparty handwriting samples. The average percentage of correct discriminations of entrance and exit writing samples was 83.7% for sentences and 67.5% for signatures, and the percentage of correct discriminations increased directly with the blood alcohol concentration of the partier who gave the writing sample. When a partier's blood alcohol concentration reached 0.15, all of the judges accurately discriminated 90% or more of the sentences, and 25 of the 28 judges correctly discriminated at least 80% of the signatures. All of the judges correctly discriminated at least 90% of the 18 sentences written by partiers with a blood alcohol concentration of 0.12 or more. Implications of these findings for reducing the risk of driving while intoxicated are discussed, as well as directions for follow-up research.

Accidents, Traffic↗
PubMed1991

Production of 5 alpha-dihydroprogesterone during late pregnancy in the mare.

Changes in the progesterone metabolite 5 alpha-dihydroprogesterone (5 alpha-DHP) in maternal plasma in late gestation, and possible sites of production of this steroid were studied in pony and Thoroughbred mares by an enzyme-linked immunosorbant assay for 5 alpha-DHP. In Thoroughbred mares, plasma 5 alpha-DHP increased from 63.7 +/- 10.5 ng/ml (27 days pre-partum) to 161.7 +/- 30.8 ng/ml (1 day pre-partum) falling to 90.2 +/- 16.1 ng/ml on the day of parturition. In pony mares, values rose from 30.8 +/- 8.1 ng/ml (27 days pre-partum) to 79.1 +/- 30.8 ng/ml (3 days pre-partum) and then decreased to 28.2 +/- 7.1 ng/ml on the day of parturition. Concentrations of 5 alpha-DHP were greater in the umbilical and uterine veins than in the corresponding umbilical and uterine artery samples. Tissues incubated with isotopically-labelled substrates showed that the fetal placenta converted pregnenolone to progesterone (47.5 +/- 9.0%). Endometrium metabolised [3H]pregnenolone to progesterone and 5 alpha-DHP (11.0 +/- 3.0% and 7.8 +/- 2.4%, respectively), and [14C]progesterone to 5 alpha-DHP (9.3 +/- 2.5%). Deuterium-labelled substrates were used to confirm the identity of these products by gas chromatography-mass spectrometry. Negligible amounts of 5 alpha-DHP were formed by other fetal tissues (adrenal, liver, kidney and testis). The results show that 5 alpha-DHP production in late pregnancy is derived primarily from endometrial metabolism of pregnenolone and/or progesterone.

5-alpha-Dihydroprogesterone↗
PubMed1990

Suitability of cryopreserved samples for pharmacological studies of ciliary activity.

The effect of terbutaline sulfate on the ciliary activity of fresh and cryopreserved human nasal epithelium was evaluated. Cryopreservation had no effect on baseline ciliary beat frequency. Both fresh and cryopreserved samples exposed to 10(-4) M terbutaline showed a statistically significant increase in ciliary beat frequency (27 and 25%, respectively). When the percentage changes after drug challenge for fresh and cryopreserved samples were compared no statistical difference emerged. It is concluded that cryopreservation in liquid nitrogen at -196 degrees C does not affect membrane receptors, at least beta-adrenergic receptors, and therefore cryopreserved samples are suitable for pharmacological studies of ciliary activity.

Adult↗
PubMed1990

Immunological features of lung lavage cells from patients with primary biliary cirrhosis may reflect those seen in pulmonary sarcoidosis.

To investigate the basis of subclinical alveolitis in patients with primary biliary cirrhosis, 10 primary biliary cirrhosis patients were studied by bronchoalveolar lavage. Both bronchoalveolar lavage lymphoid and non-lymphoid cell populations were analysed using immunocytological methods to determine their proportions and phenotypic features in an attempt to gain information as to possible immune mechanisms active in the lung of these patients. Six of the 10 patients in our study showed evidence of an alveolitis (raised lymphocyte count: 27.6 (4.3)% of total count) on lavage. The results were compared with control groups of normal volunteers and patients with active pulmonary sarcoidosis. The six primary biliary cirrhosis patients with lymphocytosis had a raised CD4/CD8 T-cell ratio (4.13:1), similar to the sarcoid patients (5.60:1). A proportion of these T-lymphocytes expressed markers of activation (HLA-DR+ 7.5 (2.1)%); CD25 + 2.3 (0.9)%; CD7 + 5.8 (1.5)%. This increased T-cell activation was also seen in the sarcoid groups (HLA-DR+ 10.0 (1.9)%; CD25 + 3.0 (1.1)%; CD7 + 5.0 (0.2)%). This was not seen in the primary biliary cirrhosis patients without lymphocytosis and the normal volunteers. Within the non-lymphoid cell population, an increase in dendritic (RFD1+) cells was seen in primary biliary cirrhosis patients with lymphocytosis (31.2 (1.9)%) and sarcoid patients (46.3 (5.1)%) in contrast with the normal and primary biliary cirrhosis group without lymphocytosis. The primary biliary cirrhosis patients without lymphocytes had a relatively greater proportion of mature phagocytes (RFD7+). We postulate that these observations suggest the emergence in the lung of a granuloma producing mechanism similar to that occurring in the liver. By comparison, the alveolitis found in primary biliary cirrhosis is consistent with that observed in interstitial granulomatous lung disorders such as sarcoidosis.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Effect of amiloride on human bronchial ciliary activity in vitro.

Amiloride (AM) reduces mucociliary transport in the frog palate in vitro preparation, whereas in vivo inhalation of AM enhances mucociliary and cough clearance in cystic fibrosis patients. AM influences the bioelectric properties of the respiratory mucosa, and since electrical activity and ciliary activity are strictly related in the beating cell, an effect on ciliary function cannot be excluded. We have, therefore, investigated the effect of AM (10(-7) to 10(-3) M) in vitro on the ciliary activity of ten samples of healthy human bronchial epithelium at 37 degrees C. The baseline ciliary beat frequency was 13.7 +/- (SD) 1.0 Hz. At concentrations of AM of 10(-4) and 10(-3) M, small statistically significant (p less than 0.01) increases in ciliary beat frequency were recorded only after 1 min of exposure to the drug, with changes of +8.2 and +7.6%, respectively. We conclude that (1) AM affects the ciliary activity of the beating cell, but (2) because of the weakness and short duration of the effect, it is unlikely that AM plays a major role on mucociliary transport.

Adult↗
PubMed1990

Alveolar targeting of aerosol pentamidine. Toward a rational delivery system.

Nebulizer systems that deposit a high proportion of aerosolized pentamidine on large airways are likely to be associated with marked adverse side effects, which may lead to premature cessation of treatment. We have measured alveolar deposition and large airway-related side effects (e.g., cough, breathlessness, and effect on pulmonary function) after aerosolization of 150 mg pentamidine isethionate labeled with 99mTc-Sn-colloid. Nine patients with AIDS were studied using three nebulizer systems producing different droplet size profiles: the Acorn System 22, Respirgard II, and Respirgard II with the inspiratory baffle removed. Alveolar deposition was greatest and side effects least with the nebulizer producing the smallest droplet size profile (Respirgard II), whereas large airway-related side effects were prominent and alveolar deposition lowest with the nebulizer producing the largest droplet size (Acorn System 22). Values for alveolar deposition and adverse airway effects were intermediate using the Respirgard with inspiratory baffle removed, thus indicating the importance of the baffle valve in determining droplet size. Addition of a similar baffle valve to the Acorn System 22 produced a marked improvement in droplet size profile. Selection of a nebulizer that produces an optimal droplet size range offers the advantage of enhancing alveolar targeting of aerosolized pentamidine while reducing large airway-related side effects.

Acquired Immunodeficiency Syndrome↗