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Biomedical subjects

D G Cook

Publications and source records attributed to D G Cook.

At least 127 records · Page 7Linked to original sources
PubMed1989

Bronchodilator action of inhaled fenoterol and ipratropium in normal subjects: a teaching exercise for medical students.

1. A pharmacology practical class for preclinical medical students was designed as a placebo-controlled, double-blind trial of two bronchodilator drugs. 2. Fenoterol hydrobromide (800 micrograms), ipratropium bromide (80 micrograms) and placebo (propellant only) were given by metered dose inhaler to 79 non-asthmatic volunteers. Their effects on FEV1, heart rate and tremor (assessed by the time taken to thread five sewing needles) were compared. 3. Both drugs caused a significant increase in FEV1: the largest group mean increase was 77 ml, recorded 15 min after fenoterol, and 103 ml, recorded 60 min after ipratropium. 4. Fenoterol also caused a mean increase of 8.7 beats min-1 in heart rate, 5 min after inhalation. This effect was still apparent after 60 min. 5. Fenoterol appeared to prolong needle threading time in some individuals. 6. In subjects who inhaled fenoterol, there were no correlations between the increase in FEV1, the increase in heart rate, or the development of tremor. 7. It is concluded that inhaled fenoterol and ipratropium both cause bronchodilation in normal subjects. Systemic absorption of fenoterol is indicated by the rapid increase in heart rate. The bronchodilator effect of ipratropium suggests that resting airway calibre is governed partly by parasympathetic tone in normal subjects. 8. The bronchodilator and systemic effects of these drugs can be used to demonstrate pharmacological, therapeutic and statistical principles to medical students.

Administration, Inhalation↗
PubMed1989

Operant conditioning of head-waving in Aplysia. I. Identified muscles involved in the operant response.

A basic goal in the neurosciences is to understand the cellular mechanisms underlying associative learning. The 2 major forms of associative learning are classical conditioning and operant conditioning. In recent years considerable progress has been made towards a cellular analysis of classical conditioning in a number of different preparations. In contrast, the cellular mechanisms underlying operant conditioning are poorly understood. Since the marine mollusc Aplysia has proved to be a powerful preparation for studying cellular and molecular mechanisms of a variety of forms of learning, including classical conditioning, we asked whether Aplysia might also be capable of exhibiting operant conditioning. In previous experiments we found that a naturally occurring behavior, the head-waving response of Aplysia, could be operantly conditioned (Cook and Carew, 1986). In the present paper we have carried out a quantitative analysis of the horizontal and vertical components of the head-waving response at the level of individual muscle groups. We have identified a discrete, bilateral band of neck muscles, the lateral columellar muscles (LCMs), whose electromyographic (EMG) activity is significantly correlated with the horizontal component of head-waving, the component modified by operant conditioning. Since head-waving is a complex behavioral response involving a variety of different muscle groups, using a restricted system such as the LCMs as an analog of the head-waving response will greatly facilitate a cellular analysis of operant conditioning in Aplysia.

Animals↗
PubMed1989

Operant conditioning of head-waving in Aplysia. II. Contingent modification of electromyographic activity in identified muscles.

Aplysia can readily exhibit operant conditioning of their head-waving response when bright light is used as aversive reinforcement (Cook and Carew, 1986). In the first paper of this series (Cook and Carew, 1989a), we showed that the electromyographic (EMG) activity of a discrete band of neck muscles, the lateral columellar muscles (LCMs) of Aplysia is significantly correlated with the component of head-waving (the horizontal component) that is modified during operant conditioning. In the present paper, we asked whether the EMG activity of the LCMs themselves could also be contingently modified, using the same procedures that produce operant conditioning of the behavioral response. Differential EMG from the LCMs was recorded in freely behaving animals with chronically implanted muscle cuff electrodes. Animals receiving aversive reinforcement (bright light) that was contingent upon specific patterns of LCM activity readily learned to alter their differential EMG output. Like operant conditioning of the head-waving response, this operant modification of LCM activity was rapidly acquired and was specific to the contingencies of reinforcement. These results show that a restricted group of muscles, the LCMs, exhibit the essential features of the head-waving system observed at the behavioral level: (1) their activity is significantly correlated with head-waving behavior, and (2) the LCMs are capable of operant modification of their output. Thus, this restricted response system provides a useful preparation for examining the neural mechanisms of operant conditioning of head-waving in Aplysia.

Animals↗
PubMed1989

Operant conditioning of head-waving in Aplysia. III. Cellular analysis of possible reinforcement pathways.

Operant conditioning of the head-waving response in Aplysia, as well as conditioning of the electrical activity of identified neck muscles, can be induced readily when bright light is used as aversive reinforcement (Cook and Carew, 1986, 1989b). A cellular analysis of this type of operant conditioning requires an understanding of the neural circuitry that underlies the reinforcement pathways involved in the conditioning. In the present paper we describe a cellular analysis of possible reinforcement pathways that mediate the aversive effects of bright light in the CNS of Aplysia. Using a semi-intact "split-body" preparation, we explored the effects of bright light on the operant response pathway by recording intracellularly from identified pedal neck and body wall motor neurons, which contribute to the operant response. In these experiments we identified 2 light-sensitive pathways. One pathway, from the eyes and rhinophores, mediated functional inhibition of light-induced excitation of pedal motor neurons. The other pathway, from the oral veil (cerebral ganglion nerves C1-C3) mediated significant excitation of the same motor cells. Randomly occurring blank trials ruled out the possibility that the light-induced effects were due to sampling bias. Finally, surgical isolation of the CNS from the periphery showed that none of the effects of light were due to direct illumination of central neurons. This identification of candidate reinforcement pathways will facilitate a cellular analysis of operant conditioning of head-waving in Aplysia.

Animals↗
PubMed1988

Blood pressure in British children: associations with adult blood pressure and cardiovascular mortality.

Blood pressure was measured in 4186 children aged 5 to 7 years in 9 British towns. 3 towns had high, 3 had intermediate, and 3 had low adult blood pressure levels observed in an earlier study of middle-aged men. Significant differences between the towns were found for the children's mean systolic blood pressure (range 96.7 to 102.4 mm Hg) and diastolic pressure (range 55.9 to 60.3 mm Hg). The pattern of systolic blood pressure differences in children was similar to that observed in the study of middle-aged men (r = 0.65). The town mean systolic pressures in children show an association with standardised mortality ratios for cardiovascular disease in adults. The pattern of geographical differences in blood pressure observed in British adult men may have its origins early in life.

Adolescent↗
PubMed1988

Reliability of eliciting physical signs in examination of the chest.

Agreement between 24 physicians on the presence or absence of respiratory signs was investigated. The physicians were divided into six sets of 4; each set examined 4 patients with well-defined chest signs. There was generally poor agreement about particular signs. Overall, the 4 physicians in a set were in complete agreement only 55% of the time. Some signs such as wheezing seemed to be more reliably elicited than others such as whispering pectoriloquy. Comparison of diagnoses based on the clinical findings with the correct diagnoses supported by investigations showed that 28% of physicians' diagnoses were incorrect. The more often the examiners differed from the majority on the presence or absence of a sign, the more likely they were to make an incorrect diagnosis. A ranked order of the reliability with which chest signs are elicited would improve the teaching of chest medicine.

Clinical Competence↗
PubMed1988

Breathlessness, lung function and the risk of heart attack.

Men with moderate or severe breathlessness had a greater than two-fold risk of suffering a major ischaemic heart disease (IHD) event compared to men with no evidence of breathlessness, based on 7.5-year follow-up in a prospective study of 7735 British men aged 40-59 years. Even after adjustment for other risk factors, including cigarette smoking, the relative risk remained two-fold. Men in the lowest fifth of the forced expiratory volume is 1 s (FEV1) distribution also had a two-fold risk of IHD compared to men in the highest fifth after similar adjustment. In part, the role of breathlessness as a risk factor for major IHD events was explained by its strong association with pre-existing, but usually undiagnosed, IHD. However, breathlessness was associated with an increased risk of heart attack even in men without any evidence of pre-existing IHD at screening. FEV1 was related to risk of a major IHD event in men without evidence of pre-existing IHD at screening and in men with previously undiagnosed IHD detected at screening. Measures of breathlessness and lung function could be more widely used in clinical situations and in screening as additional independent indicators of both unrecognized IHD and of risk for major IHD events.

Adult↗
PubMed1987

Social class differences in ischaemic heart disease in British men.

To examine why ischaemic heart disease (IHD) mortality rates in Britain are higher in manual than in non-manual workers 7735 middle-aged men in the British Regional Heart Study were followed up for 6 years, during which time 336 men experienced a major IHD event (fatal or non-fatal myocardial infarction or sudden cardiac death). The prevalence rates of IHD at screening, were higher in manual workers. Also, the attack rate of major IHD events during follow-up was 44% higher in manual workers. Marked differences in cigarette smoking contributed substantially to the increased risk of IHD in manual workers, who also had higher levels of blood pressure, were more obese, and took much less physical activity in leisure time. Adjustment for differences in these risk factors narrowed the gap between manual and non-manual workers in attack rates of IHD. Since the risk of IHD in Great Britain is high in all social classes, there would seem to be little justification for any overall policy for prevention of IHD to focus on social class. However, anti-smoking strategies might well take into account the social class differences described.

Adult↗
PubMed1987

Type A behaviour and ischaemic heart disease in middle aged British men.

The Bortner questionnaire, which measures aspects of type A (coronary prone) behaviour was completed by 5936 men aged 40-59 selected at random from one general practice in each of 19 British towns. The presence of ischaemic heart disease was determined at initial examination and the men were followed up for an average of 6.2 years for morbidity and mortality from myocardial infarction and for sudden cardiac death. Non-manual workers had significantly higher scores (more type A) than manual workers and the score decreased (less type A) with increasing age. After adjustment for social class and age men with higher scores had higher prevalences of ischaemic heart disease less marked for electrocardiographic evidence and more marked for response to a chest pain questionnaire (angina or possible myocardial infarction). A man's recall of a doctor's diagnosis of ischaemic heart disease, however, did not relate to his Bortner score. There was no significant relation between the Bortner score and the attack rate or incidence of major ischaemic heart disease events. In this study type A behaviour, as measured by the Bortner questionnaire, did not predict major ischaemic heart disease events in British middle aged men.

Adult↗
PubMed1987

Non-participation and mortality in a prospective study of cardiovascular disease.

Men who did not participate in a prospective study of cardiovascular disease (The British Regional Heart Study) were younger than the participants, more likely to be unmarried, and more likely to be less skilled workers. In the first three years of follow-up, their total mortality rate was significantly higher than that of the participants; thereafter it declined to levels not significantly different from those of the participants. This excess of early deaths could not be attributed to age. There was a small but non significant excess mortality in non-participants due to neoplasms and cardiovascular disease and a somewhat greater excess from all other causes combined. The social characteristics of the non-participant population appear to contribute to their significantly higher total mortality rate, and allowance needs to be made for this in interpreting the study findings. However the death rate from cardiovascular disease was similar in participants and non-participants, suggesting that any analysis related to this particular cause of death should not be biased by non-participation.

Adult↗
PubMed1986

Giving up smoking and the risk of heart attacks. A report from The British Regional Heart Study.

In a prospective study of 7735 middle-aged men, both current and ex-cigarette-smokers had a risk of a major IHD event, within an average 6.2 years of screening, more than twice that in men who had never smoked cigarettes; men who had given up smoking more than 20 years ago still had an increased risk. This excess risk among ex-smokers is only to a small extent explained by their higher blood pressure, serum total cholesterol, and body-mass index. An increased prevalence of IHD in men who had recently given up smoking also made a small contribution to excess risk. In both current and former cigarette smokers, the number of years a man had smoked cigarettes ("smoking-years") was the clearest indicator of IHD risk due to cigarettes. The major benefit of giving up smoking may lie in halting the accumulation of smoking years.

Adult↗
PubMed1986

Operant conditioning of head waving in Aplysia.

Head waving is a naturally occurring behavior that Aplysia use to explore their environment. Aplysia can be operantly trained to modify their head-waving response, increasing the amount of head waving on one side of their body in order to terminate the presentation of an aversive strong light. Acquisition of the operant response is rapid, within 10 min. Two observations indicate that the operant conditioning is under the control of the contingencies of reinforcement: (i) contingent reinforcement significantly elevates operant responding, reversing the contingencies significantly reduces operant performance, and reinstating the contingencies significantly reinstates operant responding; and (ii) yoked controls do not acquire the operant response, yet these same animals readily learn when reinforcement is made contingent upon their responses. Finally, internally derived cues (e.g., proprioceptive or reafferent) appear to play a predominant role in acquiring the operant response. Since progress has been made in understanding the cellular basis of classical conditioning in Aplysia, this demonstration of operant conditioning in a response system that is well-suited for a cellular analysis provides a preparation in which it is possible both to analyze the cellular mechanisms of operant conditioning and to address the theoretical question of the relationship between classical and operant conditioning on a mechanistic level.

Animals↗
PubMed1986

Serum uric acid, serum glucose and diabetes: relationships in a population study.

The relationships between serum uric acid, serum glucose and diabetes have been examined in a survey of 7735 middle-aged men drawn at random from general practices in 24 British towns. There was a positive relationship between serum glucose and serum uric acid concentrations up to about 8.0 mmol/l; at higher levels of glucose, serum uric acid decreased. Uric acid levels were significantly reduced in insulin-dependent diabetics and in those on oral hypoglycaemics and also in 'non-diabetics' with casual glucose levels greater than 10 mmol/l. Both uric acid and glucose concentrations were positively related to body mass index; only uric acid was positively related to alcohol intake. Men on antihypertensive treatment had raised levels of uric acid (significant) and glucose (non-significant). The positive relationship between serum uric acid and serum glucose could not be explained by associations with body mass index, alcohol intake, age, social class, gout or treatment for hypertension. It probably reflects the biochemical interaction between serum glucose and purine metabolism, with increased excretion of uric acid during hyperglycaemia and glycosuria.

Adult↗