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Biomedical subjects

D Grundy

Publications and source records attributed to D Grundy.

At least 19 recordsLinked to original sources
PubMed1992

Alpha-adrenoreceptor modulation of neurally evoked circular muscle responses of the guinea pig stomach.

The effects of alpha-adrenergic agonists on transmural-evoked motor responses were investigated in guinea pig gastric corpus in vitro, using preparations stripped of mucosa and orientated to record changes in circular muscle tension. Three tetrodotoxin-sensitive components to a 10 s burst of transmural stimulation could be distinguished: an initial 'on' contraction, an 'off' contraction and a transient relaxation. The 'on' response was blocked by atropine (0.1 microM), while the 'off' response and relaxation were unaffected at this dose. A submaximal dose of acetylcholine was used to assess the sensitivity of the preparation. The alpha 1 agonist L-phenylephrine decreased the amplitude of the 'off' response while simultaneously increasing both the 'on' response and the relaxation, although the response to acetylcholine was unchanged. These effects were dose-dependent and reversed by pretreatment with prazosin. In marked contrast, the alpha 2 agonist clonidine inhibited the 'on' response in a dose-dependent manner without affecting the 'off' response, the relaxation or the response to acetylcholine. Yohimbine reversed the effect of clonidine. We conclude that the inhibitory action of alpha-agonists involves both cholinergic and non-cholinergic pathways, with alpha 1 and alpha 2 adrenoceptors modulating different circuits within the enteric nervous system.

Animals↗
PubMed1992

Vertebral osteomyelitis following manipulation of spondylitic necks--a possible risk.

Neurological complications of neck manipulation are well recognised but are usually due to acute vascular incidents. However, we describe two patients with cervical spondylosis, who developed staphylococcal osteomyelitis of the cervical spine with progressive tetraplegia, apparently following manipulation of the neck by a chiropractor. Although it is possible that the manipulation resulted in cervical spine trauma sufficient to cause local haemorrhage, the area becoming a nidus for infection, it is also conceivable that the patients underwent neck manipulation in an attempt to relieve pain due to an already existing osteomyelitis of the cervical spine, and the manipulation may have hastened the onset of spinal cord paralysis. Clearly, this could have occurred, as the average time between the onset of symptoms and diagnosis of vertebral osteomyelitis in most published series is about 2 months. Approximately 80% of cases of osteomyelitis occur in the 50-70 age group, a group in which cervical spondylosis is extremely common. It would seem that neck manipulation is particularly contraindicated in older patients with cervical spondylosis.

Cervical Vertebrae↗
PubMed1992

The effectiveness of a pressure clinic in preventing pressure sores.

The role of a pressure clinic in reducing the incidence of pressure sores is described. Interface pressures are routinely measured to ensure that appropriate cushioning is provided. In patients most at risk, thermography is also valuable to ensure that the blood flow to the skin is not compromised. The implementation of such a clinic has proved successful and has resulted in a reduction of over 50% both in the incidence of sores and in the admission rate due to sores, when compared with studies from other spinal units.

Ambulatory Care Facilities↗
PubMed1992

Monitoring body fluid distribution in microgravity using impedance tomography (APT (applied potential tomography)).

For an astronaut, the excitement of going into orbit is accompanied by a shift of 1 to 1.5 l of fluid from the legs into the upper body. Information on the way the redistributed fluid is handled by the body is very useful to space physiologists studying the process of adaptation to zero-gravity. Applied potential tomography (APT) can be used to image changes in fluid distribution. To ensure that the technique was capable of measuring fluid shifts induced by changing gravitational forces on the body, a standard Sheffield APT system was used to study several subjects during the eight ESA parabolic flight campaign. The results clearly demonstrated the feasibility of using APT for monitoring fluid redistribution during space flight. A battery-powered, body-worn APT system has now been developed for use in space. The equipment was tested on the eleventh parabolic flight campaign. The data collected with the miniaturised system was comparable to that obtained in the earlier experiment. Ergonomic tests indicated that the equipment is no more difficult to operate and maintain under weightless conditions than on earth. The system is undergoing space qualification tests in Munich. If no problems arise it will be used by German astronauts on missions to MIR and Skylab.

Body Fluids↗
PubMed1992

Effect of immunisation against vasoactive intestinal polypeptide on gastric corpus tone and motility in the ferret.

The role of vasoactive intestinal polypeptide in the control of gastric corpus tone and motility was investigated using auto-antibodies to neutralise endogenous vasoactive intestinal polypeptide. Six ferrets were immunised with vasoactive intestinal polypeptide thyroglobulin conjugate in Freund's complete adjuvant which resulted in a significant increase in plasma vasoactive intestinal polypeptide binding activity compared with unimmunised control animals. In acute experiments the level of spontaneous motility in the period immediately after completion of the surgical preparation was 15 times higher in immunised v control animals (p < 0.02). Surprisingly, however, there was no deficit in the ability of the corpus to accommodate fluid. Peak pressure at the end of a 20 ml ramp distension was not different in immunised animals (5.7 (0.6) cm H2O) compared with controls (4.8 (0.3) cm H2O). It is concluded that the non-adrenergic non-cholinergic inhibitory mechanisms regulating corpus tone and motility are different and that vasoactive intestinal polypeptide acts primarily to regulate phasic contractile activity. Alternatively, because of plasticity in the mechanisms controlling corpus tone, the effect of vasoactive intestinal polypeptide may have been superceded during the timecourse of the immunisation procedure.

Animals↗
PubMed1992

Electrophysiological identification of vagally innervated enteric neurons in guinea pig stomach.

Myenteric "command neurons" are thought to be the interface between extrinsic and intrinsic controls of gut functions and are thought to be responsible for transmission of vagal impulses to enteric microcircuits. To identify, electrophysiologically, myenteric neurons responding to electrical stimulation of the vagus, we developed an in vitro preparation of the gastric myenteric plexus in which the vagal innervation was preserved. The majority of myenteric neurons [102 of 155 (66%)] received fast excitatory postsynaptic potentials (fEPSPs) after stimulation of the vagus. The proportion of neurons receiving vagal input was highest at the lesser curve (98%) and decreased gradually when recordings were made from neurons located toward the greater curve. Only a small proportion of neurons (4 of 85 cells) showed a slow EPSP after a burst of vagal stimulation. No postsynaptic inhibitory potentials were observed. There was no preferential vagal input to either gastric I, gastric II, or gastric III neurons. The fEPSPs were due to the release of acetylcholine acting postsynaptically on nicotinic receptors. The behavior of the fEPSPs suggests multiple vagal inputs to a majority of myenteric neurons. Our observations call into question the concept of enteric command neurons in favor of a divergent vagal input with widespread modulatory influences over gastric enteric neurotransmission.

Animals↗
PubMed1991

Locally and reflexly mediated effects of cholecystokinin-octapeptide on the ferret stomach.

This study was undertaken to investigate the site of origin of vagal reflexes which cholecystokinin (CCK) activates to cause reflex inhibition of gastric motility. In the anaesthetized ferret, close intraarterial injections of CCK-8 (100 pmol) caused a short latency increase in duodenal contractile activity; antral motor responses to CCK were variable, often comprising excitation followed by inhibition. The corpus, in contrast, consistently showed a decrease in pressure which lasted 2-3 min before returning to prestimulus levels. Similar responses to CCK-8 were seen in guanethidine (5 mg/kg) treated preparations, indicating that release of noradrenaline was not responsible for the relaxatory responses observed. After bilateral cervical vagotomy the duodenal response was unchanged, but the antrum showed consistent monophasic increases in tone. The response of the corpus was reversed to one of excitation, which was significantly different from prevagotomy responses (P less than 0.0001). In 10 experiments, corpus responses to CCK were tested after removal of the intestine and again after removal of the antrum. Upon removal of these segments the inhibitory motor response to CCK was reversed to one of excitation (P less than 0.01). Corpus relaxation in response to duodenal distension was significantly smaller (P less than 0.05) than that to CCK despite higher duodenal pressures during distension. Minimizing intraantral pressure changes by means of an isotonic reservoir system did not affect the response of the corpus to CCK administration. The data indicate that the inhibition of gastric motility by CCK is mediated by a direct vagal reflex and is not secondary to motility changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Vagal influences on gastric acid secretion in response to gastric distension in the ferret.

The role of the vagus nerve in the stimulation of gastric acid secretion was investigated by comparing the acid output in response to gastric distension during augmented secretion mediated by electrical vagal stimulation and pentagastrin. Under control conditions distension increased acid output from 29.8 +/- 3 mumol/10 min to 59.9 +/- 5.5 mumol/10 min (P less than 0.0001). Bilateral cervical vagotomy significantly reduced both basal acid secretion and the response to distension although the increase during distension was still significant. Electrical vagal stimulation augmented basal acid output and the response to distension, and at 1 Hz both parameters were not different from that before vagotomy. However, the sensitivity of the response to distension was unchanged by vagal stimulation. Pentagastrin infusion augmented basal acid secretion and the response to distension in a similar manner to vagal stimulation. We conclude that the vagus nerves potentiate the gastric acid secretory response to distension not by facilitating enteric reflexes but by an action at the level of the parietal cell.

Animals↗
PubMed1991

Trans-thoracic fluid shifts and endocrine responses to 6 degrees head-down tilt.

A tomographic method of measuring electrical impedance known as Applied Potential Tomography (APT) has been used to image the impedance changes within the thoraxes of 8 healthy volunteers (4 male, 4 female) during 4-h periods of 6 degrees head-down tilt (HDT). A large decrease in impedance, reflecting an increase in thoracic fluid, was apparent within 1 min of tilting, peaked after 45 min, and was maintained throughout, although during the 4 h there was an 8% return towards baseline resistivity. Resistivity changes were most obvious in the region of the lungs. Simultaneous measurements of the key fluid regulating hormones revealed a significant increase in atrial natriuretic peptide (ANP) and a significant decrease in angiotensin II (AII) and aldosterone. There was no significant difference in plasma antidiuretic hormone level. These results illustrate the dynamic nature of fluid shifts during HDT, the spatial distribution of the fluid within the thorax and the associated endocrine responses.

Adult↗
PubMed1990

Sensory and motor responses to rectal distention vary according to rate and pattern of balloon inflation.

Anorectal motor activity and rectal sensation were recorded in 12 normal male subjects during ramp distention of the rectum with water and air at randomized rates of 10, 20, 50, and 100 mL/min and during intermittent rapid distention with air. There were no significant differences between the results of ramp inflation with water or with air, and the repeated infusion of the same medium yielded reproducible results. Ramp distention induced sigmoid pressure-volume profiles. Different sensations occurred at specific points on the pressure-volume curve and were maintained until succeeded by the next sensation. Initial perception of the distention occurred during the initial steep pressure increase, the sensation of wind occurred during the plateau phase, and the desire to defecate occurred at the onset of the final rapid ascent. Rectal sensations were induced at lower volumes at low infusion rates when the slope of the pressure-volume relationship was shallower than at high infusion rates. This suggests that the receptor triggering rectal sensation is not a simple volume or pressure receptor, but is more likely to be a slowly adapting mechanoreceptor lying parallel to the circular muscle of the rectal wall. During rapid intermittent distention, the rectal volumes required to elicit rectal sensations were lower than during ramp distention, although the pressure-volume curve was steeper. Moreover, sensations often only lasted a short period of time but recurred on deflation. These data suggest activation of an additional population of rapidly adapting or high threshold mechanoreceptors. Anal relaxation was always evoked by intermittent rectal distention and was almost always associated with a rectal sensation and an increase in external anal sphincter activity. In contrast, anal relaxation could be absent or delayed during ramp inflation, especially at lower infusion rates, suggesting that internal sphincter can maintain continence for a long period of time while the rectum is slowly filling. Rectal sensation and concomitant external anal sphincter activity was not associated with anal relaxation during ramp inflation; most subjects felt the sensation long after the pressure reached its lowest level. However, under all circumstances the onset of rectal sensation was associated with an increase of external anal sphincter electrical activity. In conclusion, the rectal sensory and anorectal motor responses to distention depend on the rate and pattern of distention, which may activate a different population of receptors. Results from different laboratories cannot be compared directly unless the pattern and rate of distension are the same.

Adult↗
PubMed1990

Effects of cholecystokinin (CCK-8) on two classes of gastroduodenal vagal afferent fibre.

In order to investigate the vagal afferent pathway responsible for the previously reported effects of cholecystokinin (CCK) on gastric emptying and food intake, single afferent fibres were recorded from the cervical vagus of urethane-anaesthetized ferrets. Sixty tension receptor afferents with receptive fields in the corpus, antrum, duodenum, jejunum and ileum all showed a resting level of discharge which was augmented powerfully by distension of the segment containing the ending. Close intraarterial injection of CCK-8 (100-200 pmol) caused relaxation in proximal regions, but enhanced contractile activity in more distal regions. Mechanoreceptor discharge closely followed intraluminal pressure at all times, indicating a sensitivity primarily to tension and no direct sensitivity to CCK. Only duodenal tension receptors were significantly excited by CCK (due to increased contractile activity), whereas those in the stomach showed a net decrease. Thirty-seven mucosal receptors from the corpus, antrum, duodenum and jejunum showed responses to luminal stimuli: predominantly light stroking, acidity and hypertonicity as has been previously described. No responses to glucose or amino-acid infusions could be evoked. However, mucosal fibres showed a strong sensitivity to close-intraarterially injected CCK-8 (3-200 pmol) in 19/26 fibres tested. These responses were unaffected by cholinergic blockade when tested. The data strongly suggest that in the ferret only vagal mucosal receptors are directly sensitive to CCK-8. These fibres are therefore likely candidates for mediating some of the reflex and behavioural effects of CCK when it is released from the gastrointestinal tract and acts directly on vagal sensory endings.

Animals↗
PubMed1990

The effect of intrathecal baclofen on the lower urinary tract in paraplegia.

The effect of intrathecal baclofen on urethral pressure was investigated in 6 spinal cord injured patients. Although the response was inconsistent, and further studies are necessary to define its role more clearly in the bladder management of these patients, its possible application as an alternative to sensory rhizotomy to improve bladder emptying in patients having sacral nerve stimulation procedures is discussed.

Baclofen↗
PubMed1990

The effect of surgical anaesthesia on antral motility in the ferret.

Gastric motility was recorded from ferrets chronically prepared with an antral strain gauge. In fasted animals, antral motility showed cycles of activity and quiescence typical of the migrating motor complex (MMC) with a period of 44.7 +/- 6.1 min (n = 4). Anaesthesia with pentobarbitone sodium (50 mg/kg) disrupted this interdigestive motor pattern which returned along with recovery from anaesthesia. The first cycle of antral motility occurred 119 +/- 23.9 min after the onset of anaesthesia and thereafter continued to cycle at the pre-anaesthetic interval. The recovery was unaffected by treatment with guanethidine (2 mg/kg) or naloxone (1.25 mg/kg) but all motility was prevented with atropine (100 micrograms/kg). Following chronic truncal vagotomy cycles of antral activity persisted during pentobarbitone anaesthesia. With prolonged anaesthesia with ethyl carbamate (1300 mg/kg) there was no return to antral cycling but instead continuous low amplitude regular contractions were present. The lack of MMC activity in acute experiments is thus a consequence of the anaesthesia and not the surgical interventions.

Anesthesia↗
PubMed1990

Reflex co-ordination of corporal and antral contractions in the conscious dog.

This study characterizes the role of extrinsic nerves in the co-ordination of corporal and antral contractions in the dog. Fasting motor activity was recorded in conscious dogs with stomachs previously divided into separate corporal and antral pouches. Both corpus and antrum showed synchronized phases of activity and quiescence recognizable as migrating motor complexes (MMCs, duration 81.2 +/- 9.6 min, n = 4). Moreover, individual contractions were temporally linked such that corpus contractions, occurring at 76 +/- 4 s intervals, were each followed by a burst of one to three antral contractions at a frequency of 4-5 min-1. The mean latency between the onset of individual contractions in the corpus and antrum was 10.9 +/- 2.6 s (n = 4). Denervation of the antral pouch in two additional dogs did not affect the MMC cycle (mean durations 106.6 and 82.1 min) and the onset of activity in the corpus and antrum was generally co-ordinated but less precise. However, individual antral contractions were no longer linked to corporal contractions, occurring randomly throughout the corpus contraction cycle. This was associated with a lower contraction frequency in the denervated antral pouches than in the corpus (0.3 +/- 0.1 min-1 compared to 0.6 +/- 0.08 min-1). It is proposed that a vagal reflex, excited by corporal tension receptors, provides phasic excitation facilitating the generation of antral contractions. Such a reflex is likely to reinforce the myogenic mechanisms which occur in the intact stomach and thus plays a role in co-ordinating gastric peristalsis.

Animals↗
PubMed1989

Responses of vagal efferent fibres to stimulation of gastric mechano- and chemoreceptors in the anaesthetized ferret.

The involvement of gastric tension receptors and mucosal chemoreceptors in vagal reflexes was assessed directly by recording single efferent fibres from the cervical vagus nerve in the urethane anaesthetised ferret. 32/39 fibres responded to distension of the gastric corpus, mainly with excitation of firing, 24/39 fibres responded to antral distension, with a higher proportion showing a reduction in firing. Fifty-seven percent of fibres showed a convergent input from corpus and antrum. The magnitude of these responses was large (usually greater than 50%) and of short latency (less than 1 s). Responses to chemical perfusions in the antrum were seen in 14/31 efferent fibres, most of which showed excitation. Latency of response was variable (5-120 s) and may have been influenced by diffusion through the antral mucous barrier. These data indicate a complex arrangement of vagal reflexes involved in pre-pyloric regulation of gastric emptying by mechanical and chemical stimuli in the lumen.

Action Potentials↗
PubMed1989

Pre-pyloric mechanisms regulating gastric motor function in the conscious dog.

Reflex mechanisms regulating gastric motor function were studied in four conscious dogs, whose stomachs had been surgically divided into separate corporal and antral pouches. Interactions between the corpus and antrum were investigated in fasted animals by balloon distension of each region. During the quiescent phase (phase I) of the migrating motor complex (MMC), distending the corpus with volumes greater than 80 ml resulted in contractions of the corpus, which persisted for as long as the distending stimulus was applied. This corporal distension also initiated antral contractions which were greater if the antrum was moderately distended and also greater with a larger corporal distending volume up to 300 ml. Graded 5 ml inflation of the antrum during the quiescent phase of the MMC stimulated antral contractions. This antral response to antral distension was augmented when the corpus was inflated but was only statistically significant with antral volumes below 25 ml. Distension of the antrum with volumes greater than 12.5 ml caused inhibition of corporal contractions during both the active phase of a migrating complex or when stimulated by corporal inflation. The degree of inhibition was proportional to the distending stimulus and was present for the duration of the applied distension. For antral volumes of 50 ml the inhibition persisted for a variable time after the stimulus was withdrawn. The inhibition of corporal activity by antral distension was still effective after blocking acid secretion with cimetidine (100 mg), which would eliminate spillage of acid into the jejunum as a cause of the inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗