PubMed Health⌕ Search

Biomedical subjects

N A Saunders

Publications and source records attributed to N A Saunders.

At least 145 records · Page 8Linked to original sources
PubMed1986

Nocturnal hypoxaemia and quality of sleep in patients with chronic obstructive lung disease.

Fifty patients with chronic obstructive lung disease were questioned about their sleep quality and their responses were compared with those of 40 similarly aged patients without symptomatic lung disease. Patients with chronic obstructive lung disease reported more difficulty in getting to sleep and staying asleep and more daytime sleepiness than the control group. More than twice as many patients (28%) as controls (10%) reported regular use of hypnotics. In a subgroup of 16 patients with chronic obstructive lung disease (mean FEV1 0.88 (SD 0.44) sleep, breathing, and oxygenation were measured to examine the relationship between night time hypoxaemia and sleep quality. Sleep architecture was disturbed in most patients, arousals occurring from three to 46 times an hour (mean 15 (SD 14)/h). Arterial hypoxaemia during sleep was common and frequently severe. The mean (SD) arterial oxygen saturation (SaO2) at the onset of sleep was 91% (7%). Nine patients spent at least 40% of cumulative sleeping time at an SaO2 of less than 90% and six of these patients spent 90% of sleeping time below this level. Only four of 15 patients did not develop arterial desaturation during sleep. The mean minimum SaO2 during episodes of desaturation was less in rapid eye movement (REM) sleep (72% (17%)) than in non-REM sleep (78% (10%), p less than 0.05). The predominant breathing abnormality associated with desaturation was hypoventilation; only one patient had obstructive sleep apnoea. Arousals were related to oxygenation during sleep such that the poorer a patient's arterial oxygenation throughout the night the more disturbed his sleep (arousals/h v SaO2 at or below which 40% of the total sleep time was spent: r = 0.71, p less than 0.01). Hypoxaemia during sleep was related to waking values of SaO2 and PaCO2 but not to other daytime measures of lung function.

Female↗
PubMed1986

The effects of combined morphine and prochlorperazine on ventilatory control in humans.

Recent studies have shown that the antiemetic neuroleptic drug, prochlorperazine, is a potent stimulant of the ventilatory response to hypoxia. To investigate whether or not this effect persisted in the presence of central depression of ventilatory drive, the effects on ventilatory control of morphine with and without prochlorperazine were studied in 12 normal humans. Measurement of resting ventilation and the ventilatory responses to progressive hypercapnia and to transient asphyxia were made before and 15 min after morphine (0.15 mg/kg) given intravenously. Prochlorperazine (12.5 mg) was then administered intravenously to 6 study subjects and saline to 6 control subjects. After a further 10 min, resting ventilation and chemoreceptor function were remeasured. After the administration of morphine, resting ventilation, the ventilatory response to hypercapnia, and the ventilatory response to asphyxia were all significantly decreased (p less than 0.01 in each case; mean effect in control and study group were, respectively, -16 and -17%, -50 and -32%, -46 and -55%). Administration of saline produced no significant additional changes in the 6 control subjects. By contrast, administration of prochlorperazine to the 6 study subjects markedly increased the ventilatory response to asphyxia to levels significantly greater than postmorphine values (p less than 0.005; 2.38 +/- 0.22 L . min-1 . % Sao2 versus 0.80 +/- 0.14 L . min-1; mean +/- SEM). Resting ventilation and ventilatory response to hypercapnia were not significantly affected by prochlorperazine. These results were not explained by differences in end-tidal PCO2 at which hypercapnic hypoxic tests were performed. It is concluded that prochlorperazine reverses the depression of the ventilatory response to asphyxia caused by morphine.

Adult↗
PubMed1985

The secretion of tropoelastin by chick-embryo artery cells.

Chymotryptic fingerprint analyses of tropoelastin a and tropoelastin b demonstrated a very close relationship between these two polypeptides synthesized in a cell-free system under the direction of chick-embryo polyribosomal mRNA. A similar study on tropoelastin polypeptides extracted in their hydroxylated and under-hydroxylated forms from artery cells incubated with [3H]valine in the absence and presence of alpha alpha'-bipyridine or 3,4-dehydroproline confirmed this close relationship and suggested that tropoelastins a and b are likely to be the products of a single gene. Pulse-chase experiments in which the synthesis and secretion of tropoelastin by artery cells were monitored demonstrated that, after a pulse with [3H]proline, the polypeptides rapidly appeared in the medium and the half-time of tropoelastin secretion was approx. 30 min. Further pulse-chase studies, in which [3H]tropoelastin contents of subcellular fractions were determined, showed that rough and smooth microsomal fractions contained maximal amounts of tropoelastin at different times. The quantity of tropoelastin in the smooth-microsomal fraction was always only a small proportion of that in the rough-microsomal fraction, suggesting rapid translocation of the polypeptides to the plasma membrane. Incubation of the cells with 0.1 mM-colchicine did not markedly alter the rate of secretion or the distribution of tropoelastin between the subcellular fractions, whereas when 1 microM-monensin was included in the incubations the polypeptides were retained in the rough microsomal fraction. The results are consistent with the proposal that tropoelastin may follow a pathway of secretion from rough endoplasmic reticulum to the plasma membrane via secretory vesicles.

Animals↗
PubMed1985

The effect of central and peripheral dopamine-agonists on ventilation in the mouse.

This study was designed to investigate the role of central dopaminergic pathways in ventilatory control in unanaesthetised, chemoreceptor intact mice. Dopamine does not cross the blood-brain barrier and was used to selectively affect peripheral arterial chemoreceptors. Levodopa, the immediate precursor of dopamine, was given alone when it is converted to dopamine mainly in the periphery, and together with carbidopa, which prevents the peripheral conversion of levodopa to dopamine, and enhances central generation of dopamine from levodopa. Dopamine (60-240 mg X kg-1), levodopa (50-300 mg X kg-1), and levodopa with carbidopa in a constant ratio of 10:1 (33/3.3-100/10 mg X kg-1) were given by intraperitoneal injection. Ventilation was measured in 10% O2 and in 7.5% CO2 by a plethysmographic method. Levodopa with carbidopa stimulated ventilation in both 10% O2 and 7.5% CO2. Ventilation in 10% O2 increased from 55.1 +/- 1.43 ml X min-1 (mean +/- SE) to 93.8 +/- 4.75 ml X min-1 with levodopa 100 mg X kg-1/carbidopa 10 mg X kg-1 (P less than 0.01). Ventilation in 7.5% CO2 increased from 101.8 +/- 3.42 ml X min-1 to 138.5 +/- 4.94 ml X min-1 with levodopa 100 mg X kg-1/carbidopa 10 mg X kg-1 (P less than 0.05). In contrast, very high doses of dopamine alone (240 mg X kg-1) and levodopa alone (300 mg X kg-1) depressed hypoxic but not hypercapnic ventilation. Carbidopa alone had no effect of ventilation. It is concluded that dopaminergic transmission within the brain mediates pathways leading to increased ventilation.

Animals↗
PubMed1985

Ventilatory stimulation by dopamine-receptor antagonists in the mouse.

Ventilation was measured by a plethysmographic method in awake mice before and after intraperitoneal injection of neuroleptic drugs to test the hypothesis that dopaminergic mechanisms modulate control of breathing in this species. Dose-dependent augmentation of ventilation at rest and during hypoxia, and reduced ventilation during hypercapnia was demonstrated for haloperidol, droperidol, prochlorperazine and chlorpromazine (P less than 0.05 or less for each drug). Doses of drugs causing maximal increase of the ventilatory response to hypoxia were linearly related (r = 0.98, P less than 0.001) to in vitro affinity of the drugs for dopamine receptors. Despite presumed equal dopamine-receptor blockade, the drugs had unequal effects on the ventilatory response to hypoxia. Droperidol augmented hypoxic ventilation to 290% of the control value, chlorpromazine to 250% control, prochlorperazine to 190% control and haloperidol to 120% control. These differences in efficacy were in the same order as the affinities of the drugs for alpha-adrenoceptors. The effect of combined haloperidol (90 nmol kg-1) and varying doses of phentolamine (175-900 nmol kg-1) was assessed to test the hypothesis that alpha-antagonism was a factor in determining the increase in ventilation following dopamine blockade. Phentolamine caused dose-dependent augmentation of the ventilatory effects of haloperidol (P less than 0.01) but had no ventilatory effect when given alone. Carotid body resection in anaesthetized mice abolished the stimulation of hypoxic ventilation caused by droperidol. It is concluded that dopaminergic mechanisms in the carotid body modulate ventilatory control in the awake mouse. The drugs most effective in augmenting hypoxic ventilation are those that block both dopamine and alpha-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1984

Elastin biosynthesis in chick-embryo arteries. Studies on the intracellular site of synthesis of tropoelastin.

Electrophoretic analyses of the products of cell-free translation of elastin mRNA isolated from 17-day chick-embryo thoracic arteries have demonstrated that the elastin mRNA codes for polypeptides that are slightly larger than the cellular tropoelastin polypeptides synthesized and secreted by matrix-free artery cells. Pulse-chase experiments with cells labelled with [3H]proline established that newly synthesized tropoelastin polypeptides were associated solely with membrane-bound particulate fractions. Cell-free translation of membrane-bound and free polyribosomes isolated from artery cells revealed that the tropoelastin mRNA was associated predominantly with the membrane-bound fraction. When rough-microsomal fractions, isolated from cells labelled with [3H]proline for 10 min, were treated with proteinases in the presence and in the absence of detergent, the nascent tropoelastin polypeptides were shown to be susceptible to proteolysis only when the integrity of the membranes was destroyed by detergent treatment. In similar experiments tropoelastin polypeptides synthesized by membrane-bound polyribosomes in the nuclease-treated reticulocyte lysate were also resistant to the proteolytic-enzyme treatment. The results suggest that tropoelastin polypeptides are synthesized on membrane-bound polyribosomes and discharged into the lumen of the endoplasmic reticulum with co-translational removal of a signal peptide.

Animals↗
PubMed1984

Responses to one or two doses of a deoxycholate subunit influenza vaccine in a primed population.

A trial with a trivalent influenza subunit vaccine prepared with sodium deoxycholate was carried out in 88 volunteers between May and November 1981. Each haemagglutinin antigen was present at 7 micrograms per dose. Fourfold or greater haemagglutination inhibition antibody (HI) responses to the H1N1 virus A/Brazil/11/78 occurred in 70% of volunteers following a single dose. For the H3N2 virus A/Bangkok/1/79 and B/Singapore/222/79 these figures were 52 and 11%, respectively. No increase in the antibody titre was noted to any of the antigens following a second vaccination dose. Antibody levels remained relatively constant six months after vaccination. A response to B/Singapore/222/79, comparable with the HI response for the influenza A antigens, was noted when serum titres were estimated by a plaque reduction procedure. No neuraminidase inhibition antibody could be detected in response to either A/Brazil/11/78 or A/Bangkok/1/79. No reactions specifically attributable to the vaccine occurred after either injection. A lower HI response to A/Brazil/11/78 was noted in volunteers 52 years of age and older, who also showed less evidence of earlier priming to this virus. Levels of nasal wash neutralizing antibodies to A/Brazil/11/78 were proportional to those detected in sera by HI tests, but were present in smaller amounts.

Adolescent↗
PubMed1984

Ventilatory control in two asthmatics resuscitated from respiratory arrest.

Two female patients revived from fulminant attacks of asthma are described. Ventilatory responses to asphyxia in these patients were 0.70 +/- 0.10 l min-1 % SaO2-1 and 0.64 +/- 0.21 l min-1 % SaO2-1 (mean +/- SEM), respectively. These values were significantly less than the responses of seven normal female subjects (1.54 +/- 0.11 l min-1 % SaO2-1 mean +/- SEM; p less than 0.01). Ventilatory responses to hypercapnia of the two patients were in the low normal range. Dopamine-receptor blockade with prochlorperazine significantly increased the ventilatory response to asphyxia in normal subjects (p less than 0.05 or less for each subject) but did not alter the depressed responses in the asthmatic patients. In one patient, naloxone in a dose of 400 micrograms reversed the decreased ventilatory responsiveness; the response to asphyxia was increased from 0.72 l min-1 % SaO-1 to 1.80 l min-1 % SaO2-1 (p less than 0.01) and the response to hypercapnia was increased from 0.90 l min-1 mmHg-1 to 4.80 l min-1 mmHg-1 (p less than 0.01). Naloxone had no effect in the second asthmatic patient nor in five normal subjects. Defective chemoreceptor responses to chemical stimuli may play a role in sudden death from asthma; endogenous opioids may mediate this disorder of ventilatory control.

Adult↗
PubMed1984

Adult respiratory distress syndrome: mechanisms of lung injury.

Lung injury in the adult respiratory distress syndrome (ARDS) may be mediated through a variety of mechanisms and may involve the interaction of a number of systems involved in the inflammatory reaction--complement, granulocytes, prostaglandins and platelets. Studies in animals, involving the infusion of endotoxin, have produced convincing evidence that these agents can cause pulmonary vascular injury and a syndrome resembling human ARDS. Direct evidence of these pathogenic mechanisms in man is lacking, however, but some suggestive clues have emerged in the last few years that support this general scheme. Secondary lung injury through inappropriate fluid administration, sepsis, oxygen toxicity and barotrauma is potentially avoidable. Improved understanding of the pathophysiology of ARDS and improved hemodynamic monitoring should allow minimising of fluid administration and positive end-expiratory pressure in the management of these patients without dangerous impairment of cardiac output. Such an approach, combined with the avoidance of colloid in the early stages of the disease, and the use of vasoactive agents to support cardiac output if necessary, should minimise edema formation and barotrauma and maximise tissue oxygenation. Pulmonary sepsis continues to play an important role in ARDS. Patients are frequently infected after the initial pulmonary injury; such patients have a far worse prognosis than those who are not infected. Until ways are established at a cellular level to minimise colonisation of the upper respiratory tract, reliance must be placed on avoidance of cross infection by strict personal hygiene, avoidance of prophylactic antibiotics, and prompt, vigorous treatment of suspected pulmonary infection.

Biomechanical Phenomena↗
PubMed1983

Breathing during sleep: the responses to asphyxia and prochlorperazine in normal subjects and patients with obstructive sleep apnea.

The effects of sleep and prochlorperazine (12.5 mg intravenous bolus) on the ventilatory and arousal responses to asphyxia were studied in normal subjects and patients with obstructive sleep apnea (OSA). The ventilatory response to asphyxia was reduced during non-rapid eye movement sleep in the six normal subjects studied (1.93 +/- 0.18 l min-1.% SaO2 awake vs. 1.01 +/- 0.10 l min-1.% SaO2 asleep; mean +/- SEM; p less than 0.01) (SaO2 = arterial oxygen saturation). In the two normal subjects studied during sleep following prochlorperazine administration, ventilatory responsiveness was increased (p less than 0.05) but arousal response to asphyxia was depressed (p less than 0.025). Although prochlorperazine increased waking ventilatory responsiveness to asphyxia in five of six patients with OSA (2.26 +/- 0.44 l min-1.% SaO2 vs. 4.77 +/- 1.39 l min-1.% SaO2; mean +/- SEM; p less than 0.01), the drug had no clinically significant effect on upper airway obstruction during sleep; in three patients, apnea frequency was slightly reduced but in four of six patients severity of hypoxemia during apnea was increased with drug administration. We conclude that prochlorperazine administration is unlikely to benefit patients with obstructive sleep apnea despite its ventilatory effects during wakefulness and sleep. This lack of effect may be explained by separate effects of the drug on ventilatory and arousal responses to asphyxia.

Adult↗
PubMed1982

Hypersensitivity pneumonitis in a mouldy house.

Two cases of hypersensitivity pneumonitis, one confirmed by histopatholgy, are described. The patients were members of different families and developed the disease as occupants, at separate times, of the same inner-city dwelling. We believe the disorder resulted from exposure to thermophilic microorganisms prevalent in their domestic environment. Both patients recovered after moving from this place of residence. The need for greater awareness of this variety of hypersensitivity pneumonitis is stressed.

Adult↗
PubMed1982

Augmentation of ventilatory response to asphyxia by prochlorperazine in humans.

The effect of the dopamine-receptor blocking agent prochlorperazine on the ventilatory response to hypercapnic hypoxia was studied in six healthy adults. Repeated episodes of transient hypoxia were induced at the mixed venous PCO2 level by a nonrebreathing technique in five males and one female before and after an intravenous bolus injection of prochlorperazine mesylate (12.5 mg = 10 mg base). The ventilatory response to CO2 was also studied before and after drug administration. Prochlorperazine produced a modest (15%) increase in resting ventilation (P less than 0.05) but a marked increase in the ventilatory response to asphyxia such that the group mean response was double the control value [2.0 +/- 0.7 vs. 4.2 +/- 1.5 l . min-1 . % arterial O2 saturation (%SaO2); P less than 0.001]. Two-thirds of this change in ventilatory response was due to an increase in frequency response to hypoxia (0.34 +/- 0.20 vs. 0.81 +/- 0.52 breaths . min-1 . %SaO2; P less than 0.001). The position of the ventilatory response line, as judged by the computed ventilation at 95% SaO2, was increased by prochlorperazine (22.2 +/- 9.6 vs. 35.9 +/- 10.9 l . min-1; P less than 0.01) due to an increase in both tidal volume (P less than 0.05) and frequency of breathing (P less than 0.0125). The ventilatory response to CO2 was unchanged by drug injection. In separate experiments prochlorperazine was shown to 1) increase the ventilatory response to steady-state eucapnic hypoxia (P less than 0.01) demonstrating that the drug effect was not dependent on either the presence of hypercapnia or rapidly changing states of arterial oxygenation; and 2) reverse the depressant effect of intravenously infused dopamine hydrochloride (5 micrograms . kg-1 . min-1) on the ventilatory response to transient asphyxia (P less than 0.01). We conclude that prochlorperazine augments hypoxic responsiveness in humans. The mechanism may be blockade of dopaminergic receptors that modulate carotid body discharge.

Adult↗
PubMed1982

Ventilatory responsiveness to hypercapnic hypoxia during dopamine infusion in humans.

The effect of dopamine on the ventilatory response to transient asphyxia was examined to test the hypothesis that dopaminergic mechanisms modulate carotid body function in humans and to determine whether a change in ventilatory responsiveness is effected by changes in tidal volume or breathing frequency. Five healthy adults were subjected to brief episodes of hypercapnic hypoxia before and at the end of a 45-min intravenous infusion of dopamine hydrochloride (5 micrograms/kg/min). Mean ventilatory response to hypercapnic hypoxia decreased from 1.71 +/- 0.33 L/min/% SaO2 (+/- SD) to 1.30 +/- 0.28 L/min/% SaO2 (p less than 0.05) during dopamine infusion. The fall in ventilatory response was due to a fall in the frequency of breathing (p less than 0.01). Dopamine infusion also produced a small decrease in resting minute ventilation (p less than 0.05) and a small increase in resting end-tidal PCO2 (p less than 0.05). No change was noted in the ventilatory response to progressive hypercapnia. These findings suggest that dopamine acts at the carotid body to depress its response to transient hypoxic stimulation and that this effect is to selectively slow the rate of breathing.

Adult↗
PubMed1981

Progesterone administration and progressive sleep apneas.

Nine adult patients with obstructive sleep apnea syndrome were administered medroxyprogesterone acetate, 60 to 120 mg/day, and the effect of medroxyprogesterone on clinical symptoms and obstructive apneas during sleep was assessed. Four patients responded with resolution of daytime sleepiness, disappearance of pedal edema, and a decrease in the number of obstructive apneas during sleep. Cessation of therapy led to a return of daytime sleepiness in three and an increase in obstructive apneas in all four subjects. Two responders experienced side effects of alopecia or decreased libido. Before medroxyprogesterone therapy, responders were distinguished from nonresponders only by the presence of a significantly lower resting arterial oxygen tension during wakefulness. We characterize a subgroup of patients who benefit from medroxyprogesterone therapy by reducing obstructive apneas during sleep.

Adult↗
PubMed1981

Learning decision-making in clinical medicine: a card game dealing with acute emergencies for undergraduate use.

A card game concerning the assessment and management of patients involved in medical emergencies was constructed for use by medical students who were beginning Year 3 of a 5-year curriculum. Particular emphasis was place on the identification by the student of priorities for action and the justification for decisions made on the basis of underlying mechanisms. Our aim was to help the student sharpen his problem-solving skills in situations where decisions may have to be made and interventions undertaken before information gathering is complete. The game is simple in construct and may be played by individuals or groups. It has a major advantage over other forms of problem presentation in that the student can select and document his own decision-making pathway with minimal cueing and he may compare his pathway with that of the experts at the end of the game. Students and tutors found this approach enjoyable and realistic and considered the game a useful tool in our problem solving curriculum.

Australia↗