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Biomedical subjects

A G Turner

Publications and source records attributed to A G Turner.

At least 37 records · Page 2Linked to original sources

Effects of aging on the responsiveness of the human cardiac sympathetic nerves to stressors.

BACKGROUND: Aging increases human sympathetic nervous activity at rest. Beause of the probable importance of neural stress responses in the heart as triggers for clinical end points of coronary artery disease, it is pertinent to investigate whether sympathetic nervous responses to stresses are increased by aging. METHODS AND RESULTS: We applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20 to 30 years) and older (aged 60 to 75 years) healthy men during mental stress (difficult mental arithmetic), isometric exercise (sustained handgrip), and dynamic exercise (supine cycling). The increase in total norepinephrine spillover to plasma with mental stress was unaffected by age. In contrast, the increase in cardiac norepinephrine spillover was two to three times higher in the older subjects (P < .05). The probable mechanism of this higher cardiac norepinephrine spillover was reduced neuronal reuptake of the transmitter, because age had no influence on the overflow of the norepinephrine precursor, dihydroxyphenylalanine, or intraneuronal metabolite, dihydroxyphenylglycol (levels of these two substances reflect rates of cardiac norepinephrine synthesis and intraneuronal metabolism), and the transcardiac extraction of plasma radiolabeled norepinephrine was lower in the older subjects (P < .05). An almost identical pattern of neurochemical response was seen with isometric exercise. During cycling, total norepinephrine spillover was 16% lower in the older men, but cardiac norepinephrine spillover was 53% higher. CONCLUSIONS: Reduced norepinephrine reuptake increases the overflow of the neurotransmitter to plasma from the aging heart during stimulation of the cardiac sympathetic outflow. Failure of transmitter inactivation at postjunctional receptors with aging would amplify the neural signal, and in the presence of myocardial disease could trigger adverse stress-induced cardiovascular events, particularly when accompanied by an age-dependent reduction in vagal tone. Reduction of postsynaptic adrenergic responsiveness with aging, however, might protect against this, as indicated by our finding that in no case was the heart rate increase during stress greater in older men, despite their having larger increases in cardiac norepinephrine spillover.

Adult↗

Central nervous system noradrenergic and dopaminergic turnover in response to acute neuroleptic challenge.

The objective of this study was to obtain direct neurochemical measures of the central nervous system's response to a typical neuroleptic, haloperidol, in human subjects. Nine healthy volunteers participated in this study. Central nervous system neuronal activity was assessed by measuring the plasma concentration and overflow from the brain of dopamine, norepinephrine, and their lipophilic and acidic metabolites after acute intravenous administration of haloperidol. By combining bilateral internal jugular vein blood sampling with cerebral blood flow scans we were able to differentiate between cortical and subcortical responses to haloperidol. The central nervous system response to haloperidol administration displayed a degree of regional specificity. Dopamine release, estimated from the overflow of homovanillic and dihydroxyphenylacetic acids, was reduced in cortical but not subcortical brain regions. Norepinephrine turnover was increased in cortical and subcortical brain regions. The overflow of homovanillic acid from the brain into the internal jugular veins was not related quantitatively to the arterial plasma concentrations of the catecholamines examined, homovanillic and dihydroxyphenylacetic acids or prolactin. Measurements of catecholamines and their metabolites in arterial plasma gave little indication as to monoaminergic neuronal activity in the brain.

Adolescent↗

Regional 5-hydroxyindoleacetic acid production in humans.

Veno-arterial plasma concentration differences and regional organ plasma flows were used to quantify the relative amounts of 5-hydroxyindoleacetic acid (5-HIAA) contributed by various sites into the peripheral circulation. Positive venoarterial concentration gradients were found in the hepatosplanchnic, forearm, cardiac and jugular vessels in the healthy subjects. The renal circulation was determined to be the principal site of 5-HIAA clearance, extracting 18 +/- 2 nmol/min. The gut was the greatest contributor to the total 5-HIAA plasma pool with the relative contributions of the various organs being as follows: hepatosplanchnic organs 58%, skeletal muscle 26%, brain 6% and the heart 3%. The source of 5-HIAA stemming from these regional beds remains unknown, it may derive from serotonin taken up by and deaminated in ubiquitous endothelial cells, enterochromaffin cells of the gut, peripheral serotonergic nerves, serotonin turnover in platelets or perhaps the metabolism of serotonin taken up by sympathetic nerves. To test the latter hypothesis we examined 23 patients with chronic congestive heart failure and 9 patients with pure autonomic failure to investigate the possible effects of sympathetic nervous system overactivity and underactivity on peripheral 5-HIAA production and plasma 5-HIAA concentration. The resting arterial plasma 5-HIAA concentration in the heart failure patients was increased three-fold. This elevated plasma 5-HIAA concentration was attributable to an increased rate of whole body 5-HIAA production. The arterial 5-HIAA plasma concentration in the autonomic failure patients was paradoxically elevated, being 70% greater than that of the healthy subjects. The increased 5-HIAA plasma concentration in these patients was accounted for by a reduction in 5-HIAA plasma clearance. In all subjects studied there was a weak relationship only between total body norepinephrine spillover to plasma and the arterial 5-HIAA plasma concentration. We found that in healthy subjects the overflow of 5-HIAA into the hepatic vein was significantly related to the underlying degree of sympathetic activity. It can be concluded that 5-HIAA is produced at a number of sites throughout the body with the arterial plasma concentration being dependent on both the level of production and plasma clearance. By far the majority of 5-HIAA in plasma is derived from the gut with only minimal contribution from the brain.

Adolescent↗

Regional sympathetic nervous activation after a large meal in humans.

1. To investigate the link between post-prandial thermogenesis and sympathetic nervous activation we have studied the effects of a single large meal on regional sympathetic nervous activity in healthy, lean subjects. 2. In nine male subjects, noradrenaline spillover was measured from the heart, kidney and liver using isotope dilution, both while fasting and after consumption of a high-energy liquid meal of composition 53% carbohydrate, 32% fat and 15% protein (energy value 2.64-3.51 MJ). Regional oxygen consumption, whole-body oxygen consumption and, in a subset of subjects, muscle sympathetic nerve firing (microneurography) were also measured. 3. Both whole-body oxygen consumption (P < 0.03) and total body spillover of noradrenaline (P < 0.01) rose after the meal, with peak increases of 24% and 56% respectively. Spillover of noradrenaline from the heart was unchanged, that from the hepatosplanchnic circulation increased marginally (0.377 nmol/min to 0.480 nmol/min, P = 0.09), while renal noradrenaline spillover more than doubled (0.440 nmol/min to 0.937 nmol/min, P < 0.05). Skeletal muscle sympathetic nerve activity (peroneal nerve) increased from 7.7 bursts/min at rest to peak at 17.9 bursts/min 60 min after the meal in the three subjects in whom stable recordings were obtained. 4. The meal increased oxygen consumption in the kidneys and liver significantly, from 11.5 +/- 1.6 ml/min to 14.5 +/- 1.1 ml/min and from 46 +/- 7 ml/min to 57 +/- 6 ml/min respectively (P < 0.05), but not in the heart. 5. Consumption of a large meal produces a substantial and relatively selective increase in sympathetic outflow to the kidneys and skeletal muscle. While resting regional oxygen consumptions and noradrenaline spillovers were related, the changes that occurred in each were unrelated, so that no direct relationship could be demonstrated between postprandial thermogenesis and sympathetic activity.

Adolescent↗

Aging effects on human sympathetic neuronal function.

To study the effect of aging on human sympathetic nervous function, we applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20-30 yr) and older (aged 60-75 yr) healthy men. Mean plasma norepinephrine concentration was 66% higher in older men, attributable to 22% lower norepinephrine plasma clearance (P < 0.05) and 29% higher norepinephrine spillover to plasma (difference not statistically significant). Regional venous sampling disclosed that sympathetic outflow to all organs was not activated by aging. Renal norepinephrine spillover was normal in older men. Although spillover of norepinephrine from the heart was increased in older men, 21.1 +/- 11.4 ng/min compared with 11.4 +/- 8.6 ng/min (P < 0.05), diminished norepinephrine reuptake rather than increased cardiac sympathetic nerve firing was the most likely cause, although somewhat reduced intracardiac methylation of norepinephrine with aging also possibly contributed. The extraction of tritiated norepinephrine from plasma during transit through the heart was reduced, suggesting neuronal norepinephrine reuptake was lowered and overflow of the norepinephrine precursor dihydroxyphenylalanine and metabolites dihydroxyphenylglycol and 3-methoxy-4-hydroxy phenylglycol was normal, indicating that norepinephrine synthesis and release were not increased.

Adult↗

Fatherhood without apparent spermatozoa after vasectomy.

Fatherhood after vasectomy is rare. We describe 6 cases of DNA-proven fatherhood after vasectomy in association with persistently negative semen examination. All vasectomy patients and their partners should be counselled about the small possibility of late failure, and warning of failure should be recorded.

Female↗

Light-harvesting chlorophyll c-like pigment in Prochloron.

A chlorophyll c-like pigment, similar to magnesium-3,8-divinyl pheoporphyrin a5 monomethyl ester, has been isolated from Prochloron sp. obtained from five species of didemnid ascidians from the Great Barrier Reef, Australia, and from Palau, Micronesia. The pigment represents 4-15% of the total chlorophyll content and is shown to function in a light-harvesting pigment protein complex of Prochloron. The observation that all of the major chlorophylls (a+b+c) function in a light-harvesting role in Prochloron and possibly in other prochlorophytes is discussed in terms of the phylogeny of the prochlorophytes.

Journal Article↗

Massive intraperitoneal hemorrhage associated with renal pathology.

We report on 2 patients who presented with massive intraperitoneal hemorrhage. In spontaneous renal hemorrhage there is often an underlying pathological condition, usually renal carcinoma. The investigation of choice is computerized tomography, while arteriography is reserved for cases in which no renal mass is found. Nephrectomy may be life-saving but conservative treatment is an acceptable alternative when the underlying pathological condition is benign and the patient is in stable condition.

Aged↗

A comparison of two radiotherapy regimens for the treatment of symptoms from advanced bladder cancer.

Pain and haematuria are two of the most distressing symptoms in patients with advanced bladder cancer. The aim of palliative radiotherapy is to relieve these symptoms with the minimum of stress to the patient and with minimal side effects. Two treatment regimens were studied: hypofractionated radiotherapy giving 1700 cGy in two fractions over 3 days and conventional palliative radiotherapy giving 4500 cGy in 12 fractions over 26 days. This study assesses 41 patients, all with Grade II-III T3-4 transitional cell carcinomas of the bladder treated between 1982 and 1989, presenting with haematuria and local pain. Two-fraction (hypofractionated) treatment was given to 22 patients and conventional palliative radiotherapy to 19; patients were selected by performance status. The effect on haematuria was assessed as cleared, intermittent or persistent. Pain was assessed by noting reduction in the need for opiate analgesia. Any side effect was recorded. In the patients receiving two-fraction radiotherapy, 59% had clearance of the haematuria and in 73% there was improvement of their pain, compared with 16% and 37% respectively in those receiving conventional palliation. Survival of the two groups was 9.77 months and 14.47 months respectively. Side effects were trivial in both regimens. Radiotherapy given in two fractions for patients in poor general health is well tolerated and less distressing than the standard palliative regimen with 12 fractions. Haematuria and pain were more effectively palliated than with conventional treatment, though survival was shorter. We conclude that hypofractionated radiotherapy may be the palliative treatment of choice and the study supports the need for a prospective assessment of this treatment approach.

Aged↗

Monoaminergic neuronal activity in subcortical brain regions in essential hypertension.

In this study we aimed to elucidate the role of central noradrenergic, dopaminergic, adrenergic and serotonergic neuronal systems in the development of essential hypertension. Fifteen untreated essential hypertensive subjects (aged 44 +/- 3 years) and 32 healthy volunteers (aged 38 +/- 3 years) participated in this study. By combining direct blood sampling techniques with cerebral blood flow scans we were able to differentiate between cortical and subcortical venous drainage of the brain. Veno-arterial MHPG, HVA and 5-HIAA plasma concentration gradients combined with internal jugular vein plasma flows were used, according to the Fick Principle, to derive metabolite spillovers which in turn were used as indicators of central noradrenergic, dopaminergic and serotonergic neuronal activity, respectively. These amine systems, in both the brainstem and forebrain, have been implicated in the regulation of sympathetic outflow and blood pressure. Total body noradrenaline spillover to plasma was concurrently measured to assess the relationship between central monoamine turnover and sympathetic activity. Compared to their healthy counterparts the hypertensive subjects had an elevated release of MHPG from subcortical brain regions (1.4 +/- 0.3 v 0.5 +/- 0.2 nmol/min, p < 0.05). An inverse relationship between blood pressure and subcortical HVA overflow existed, with the HVA overflow being significantly lower in the hypertensives (0.5 +/- 0.2 v 2.1 +/- 0.5 nmol/min, p < 0.05). Subcortical 5-HUAA overflow did not differ between the two groups, and adrenaline spillover from the brain was not detected in either group. Subcortical MHPG overflow was significantly correlated with total body NA spillover to plasma (p < 0.05). These results indicate that reciprocal aberrations in subcortical noradrenaline and dopamine turnover exist in essential hypertension. Although the physiological significance of this remains to be unequivocally elucidated we postulate that elevated subcortical noradrenergic activity, presumably in the forebrain where noradrenergic neurons are pressor, may cause sympathoexcitation and play a role in the development of essential hypertension.

3,4-Dihydroxyphenylacetic Acid↗

Are patients' attitudes the cause of long waiting lists?

This paper studies the rate of non-attendance for both out-patient clinics and in-patient care. It relates this to the waiting times for both services. If all patients who did not attend clinics had informed us beforehand, thus enabling us to give their appointments to other patients, the out-patient waiting time could have been reduced from six months to one week. If a similar approach was taken with the in-patient waiting list, the waiting time could have been reduced from 15 months to nine months.

Appointments and Schedules↗

Pelvic injuries associated with traumatic abduction of the leg.

We report a series of six severe pelvic injuries associated with traumatic abduction of the leg. All sustained a severe fracture of the pelvis associated with a deep perineal wound extending into the anus. Laparotomy was usually required to control haemorrhage and packing was only effective once the pelvis had been stabilized by external fixation. A sigmoid loop colostomy was required in all five initial survivors because of sphincter disruption, but three out of four long-term survivors are now fully continent. If mortality is to be reduced, blood loss must be rapidly controlled and sepsis prevented.

Accidents, Traffic↗

Comparison of two biological aerosol sampling methods.

Two biological aerosol samplers, the Andersen two-stage microbial impactor and the May three-stage glass impinger, were examined to determine the benefits and effectiveness of the May sampler compared with the Andersen sampler, one of the most widely accepted samplers. Side-by-side samples were collected during simulated wastewater spray irrigation dispersion studies. Escherichia coli colony counts and air concentrations were statistically treated to determine the dependability of the May results with respect to the Andersen results. After data pairs containing potentially overloaded Andersen counts were eliminated, a linear regression of the remaining data was performed. It indicates that although the May sampler reports 82% of the Andersen sampler value, the correlation between the two samplers is good with an r2 value of 0.84. This comparison indicates that although there are differences between the two samplers, they do give comparable results and that when both are used in a sampling program, they tend to complement each other.

Air Microbiology↗