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Biomedical subjects

J Dent

Publications and source records attributed to J Dent.

At least 19 recordsLinked to original sources

Computer system for assisting with clinical interpretation of tumour marker data.

OBJECTIVE: To design and evaluate a computer advisory system for the treatment of gestational trophoblastic tumour. DESIGN: A comparison of clinicians' treatment decisions with those of the computer system. Two datasets were used: one to calibrate the system and one to independently evaluate it. SETTING: Department of medical oncology. PATIENTS: Computerised records of 290 patients with low risk gestational trophoblastic tumour for whom the advisory system could predict the adequacy of treatment. The calibration set comprised patients admitted during 1979-86(227) and the test set patients during 1986-89(63). MAIN OUTCOME MEASURES: The system's accuracy in predicting need to change treatment compared with clinicians' actions. The mean time faster that the system was in predicting the need to change treatment. RESULTS: On the calibration dataset the system was 94% (164/174) accurate in predicting patients whose treatment was adequate, recommending change when none occurred in only 10 (6%) patients. In patients whose treatment was changed the system recommended change earlier than clinicians in 39/53 cases (74%), with a mean time advantage of 14.9 (SE 2.02) days. On the test dataset the system had an accuracy of 91% (31/34) in predicting treatment adequacy and a false positive rate of 9% (3/34). The system recommended change earlier than clinicians in 22/29 cases (76%), with a mean time advantage of 12.5 (2.22) days. CONCLUSIONS: The computer advisory system could improve patient management by reducing the time spent receiving ineffective treatment. This has implications for both patient time and clinical costs.

Biomarkers, Tumor

Muscle excitation in elderly adults: the effects of training.

Muscle membrane excitability is thought to decline with aging; the extent of this decline may be noninvasively assessed by measurement of the electrically evoked compound muscle action potential (M-wave). The intent of this study was two-fold: (1) to compare the M-wave in the brachioradialis (BR), tibialis anterior (TA), and thenar (TH) muscles of elderly (mean age = 66.3 +/- 3.7 years) and young (mean age = 31.2 +/- 4.9 years) adults, and (2) to determine the effects of 12 weeks of resistance training on M-wave characteristics in elderly adults. Prior to training, the elderly subjects had significantly smaller (P less than 0.05) resting M-waves than the young adults in the BR (4.8 mV vs. 8.7 mV), TA (8.8 mV vs. 11.0 mV), and TH (5.2 mV vs. 10.2 mV) muscles. During a 2-minute voluntary fatigue paradigm (3 seconds MVC per 2 seconds rest for 2 minutes), there was no evidence of excitability failure in either group. Following training, there was a significant increase (P less than 0.05) in the size of the M-wave of the TH (pretraining: 5.2 mV; posttraining: 8.96 mV) and BR (pretraining: 4.8 mV; posttraining: 6.1 mV), and a nonsignificant increase in the M-wave of the TA, but there was no change in the relative behavior of the M-wave during the 2-minute voluntary fatigue paradigm. It is suggested that the decline in muscle membrane excitation with aging may be due, at least in part, to the effects of a decreased membrane potential on the muscle fiber action potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

Influence of sleep on anal sphincteric pressure in health and after ileal pouch-anal anastomosis.

Fecal incontinence at night may be a disturbing consequence of ileal pouch-anal anastomosis (IPAA). The hypothesis was that decreases in anal canal resting pressure occur as sleep deepens and that the decreases are more profound in pouch patients with incontinence than in controls. Using a sleeve catheter assembly for recording intraluminal and canal pressure and polysomnographic recordings of sleep stages, progressive decreases in anal canal resting pressure with deepening sleep occurred in 11 healthy controls (mean +/- SEM: 57 +/- 3 mm Hg to 43 +/- 3 mm Hg: P less than 0.05) and in 11 patients after IPAA (55 +/- 3 mm Hg to 42 +/- 4 mm Hg; P less than 0.05). Minute-to-minute variations in mean pressure were also found in both controls and IPAA patients, and they were greater at night in patients (P less than 0.05), except during rapid eye movement (REM) sleep. In three patients, resting pressure during REM sleep decreased markedly to 31 +/- 8 mm Hg. This decrease plus the variations in pressure during REM sleep led to incontinence. In conclusion, decreases in anal resting pressure coupled with marked minute-to-minute variations in pressure during sleep occurred in controls and in patients after IPAA and, when profound, led to nocturnal fecal incontinence in some patients.

Adult

Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility.

The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P less than 0.003) and tonic (P less than 0.002) pyloric pressure waves and stimulated antral (P less than 0.003) and duodenal pressure waves (P less than 0.02). After erythromycin antral pressure waves were usually of high amplitude (greater than 50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin.

Adult

Adaptive changes in the pyloric motor response to intraduodenal dextrose in normal subjects.

Gastric emptying of glucose is faster after dietary supplementation of glucose, suggesting specific adaptation to changes in nutrient intake. In the present study, the effects of a continuous long-term (0-120-minute) and two short-term (0-20- and 80-100-minute) intraduodenal infusions of dextrose (2.4 kcal/min) on antropyloroduodenal motility and blood glucose, plasma gastric inhibitory polypeptide, and insulin concentrations were evaluated in nine volunteers. In four volunteers, an intraduodenal infusion of triglyceride (2.4 kcal/min) was administered immediately after the long-term dextrose infusion. The long-term dextrose infusion initially increased isolated pyloric pressure waves (IPPWs) and basal pyloric pressure (P < 0.05 for both), but after about 30 minutes IPPWs and basal pyloric pressure decreased and returned to baseline within 80 minutes. Each short-term infusion increased IPPWs and basal pyloric pressure (P < 0.05 for both). Antral pressure waves remained suppressed during the long-term dextrose infusion. Intraduodenal triglyceride increased IPPWs and basal pyloric pressure (P < 0.05 for both). The long-term dextrose infusion was associated with a sustained increase, and both short-term dextrose infusions were associated with peaks in glucose, insulin, and gastric inhibitory polypeptide levels. There was no significant relationship between biochemical measurements and antropyloroduodenal motility. It is concluded that specific adaptive changes occur rapidly in the phasic and tonic pyloric motor response, but not the antral motor response, to intraduodenal dextrose.

Adaptation, Physiological

Pharyngeal (Zenker's) diverticulum is a disorder of upper esophageal sphincter opening.

Pharyngeal coordination, sphincter opening, and flow pressures during swallowing were investigated in patients with pharyngeal (Zenker's) diverticula. Fourteen patients with diverticula and 9 healthy age-matched controls were studied using simultaneous videoradiography and manometry. Pharyngeal and upper esophageal sphincter pressures were recorded by a perfused side hole/sleeve assembly. Temporal relationships among swallowing events, extent of sphincter opening during swallowing, and intrabolus pressure during bolus passage across the sphincter were measured. The timing among pharyngeal contraction and sphincter relaxation, opening, and closure did not differ between patients and controls. Sphincter opening was significantly reduced in patients compared with controls in sagittal (P = 0.0003) and transverse (P = 0.005) planes. Manometric sphincter relaxation was normal in patients. Intrabolus pressure was significantly greater in patients than in controls (P = 0.001). It is concluded that Zenker's diverticulum is a disorder of diminished upper esophageal sphincter opening that is not caused by pharyngosphincteric incoordination or failed sphincter relaxation. Incomplete sphincter opening is likely to cause dysphagia. Increased hypopharyngeal pressures during swallowing are probably important in the pathogenesis of the diverticulum.

Aged

Relation of pyloric motility to pyloric opening and closure in healthy subjects.

The relation between pyloric motor activity, opening, and closure was examined in eight healthy men. Manometry was performed with an assembly combining 13 side holes and a sleeve sensor positioned astride the pylorus. Simultaneous with manometry, pyloric opening and closure and antroduodenal contractions were observed fluoroscopically with the antrum filled with barium. During intraduodenal normal saline infusion, coordinated antral pressure waves swept over the pylorus and ejected barium into the duodenum. No localised pyloric motor pattern was observed under these conditions. In contrast, the intraduodenal triglyceride infusion was associated with the absence of antral pressure waves and virtual absence of antral wall movement. At the pylorus, there was a zone of luminal occlusion less than 1 cm long that persisted for the period of observation. This zone of luminal occlusion corresponded precisely with manometric recordings of a narrow zone of pyloric phasic and tonic activity. During the duodenal triglyceride infusion, the pylorus was closed for 98.5% of the measurement period when basal pyloric pressure was 4 mm Hg or more, and during this motor pattern, barium did not traverse the pylorus. Localised pyloric contractions cause sustained pyloric closure, whether these contractions are phasic or tonic. These contractions occur independently of antral or duodenal contractions and may interrupt gastric emptying.

Adult

Duodenal intramural nerves in control of pyloric motility and gastric emptying.

We have investigated the role of ascending duodenal intramural nerves in the control of isolated pyloric pressure waves (IPPW) and liquid gastric emptying. In six pigs, the proximal duodenum was transected to interrupt intramural nerves. A further six pigs had a sham operation. Four weeks after operation, motility of the antrum, pylorus, and duodenum was recorded by side holes and a sleeve sensor. Gastric emptying of a 1,000-ml test meal was significantly more rapid in duodenum-transected animals (P less than 0.0001) during intraduodenal infusion of each of isosmolar dextrose (424 ml emptied), fatty acid (335 ml), and amino acids (396 ml) than in duodenum-intact animals (dextrose: 128 ml; fatty acid: 57 ml; amino acids: 192 ml). Associated with this, in duodenum-transected animals infusion of each of isosmolar dextrose, fatty acid, amino acids, and hyperosmolar saline failed to produce the stimulation of IPPW seen in duodenum-intact animals. In both duodenum-intact and -transected animals, supramaximal stimulation by intraduodenal infusion of 25% dextrose slowed gastric emptying and stimulated IPPW. Ascending duodenal intramural nerves are a major physiological pathway for nutrient- and osmolar-stimulated feedback control of pyloric motility and gastric emptying.

Animals

Changes in antroduodenal resistance induced by Cisapride in conscious dogs.

The effects of Cisapride on gastric outflow/pressure relationships have been examined in conscious dogs. In the digestive state, after inhibition of emptying in the first 10 min, Cisapride accelerated gastric emptying for 110 min by increasing the volume (7.3 +/- 1.2 vs. 2.3 +/- 0.3 ml) rather than by decreasing the interval between flow pulses (4.9 +/- 0.2 vs. 4.5 +/- 0.1s). After non-nutrient gastric loading, Cisapride also first inhibited and then accelerated gastric emptying as the consequence of both a larger stroke volume (8.0 +/- 1.7 vs. 3.2 +/- 0.5 ml) and more frequent pulses (3.9 +/- 0.1 vs. 4.9 +/- 0.1 s). In both situations, Cisapride increased the amplitude of the antral/pyloric pressure waves. Antropyloroduodenal resistance increased substantially in the first 10 min after Cisapride then recovered to its control value. We conclude that stimulation of antropyloroduodenal motility by Cisapride can both impede and increase gastric emptying by changes in antroduodenal resistance.

Animals

Diaphragmatic contribution to gastroesophageal competence and reflux in dogs.

Events associated with gastroesophageal reflux have been determined by concurrent diaphragmatic and esophageal body electromyography, video radiography, and manometry in four conscious dogs. Three characteristic phenomena occurred in parallel immediately before and during gastroesophageal reflux: 1) transient lower esophageal sphincter relaxation, 2) profound (99.5%) and selective inhibition of crural diaphragmatic activity, and 3) a previously unrecognized dorsal movement of the gastroesophageal junction (mean 1.3 cm) demonstrated by implanted radiological markers. The patterns associated with spontaneous acid and gas reflux were indistinguishable from those induced by gastric distension. Costolumbar diaphragmatic activity was stable up until the instant of sphincter opening, when there was a single costolumbar contraction of short duration and high amplitude. Esophageal shortening did not occur before reflux. Reflux that occurred after atropine-induced inhibition of lower esophageal sphincter tone to < 2 mmHg was intermittent and coincided with selective crural inhibition. These studies demonstrated that selective crural inhibition is a prerequisite for gastroesophageal reflux and suggest that the crural diaphragm is an important factor for the maintenance of gastroesophageal competence.

Animals

Long-term aims of treatment of reflux disease, and the role of non-drug measures.

Recent opinion about the long-term aims of treatment of reflux disease has been influenced substantially by the development of highly effective drugs that have minimal side-effects. The success of these drugs has emphasized the importance of gains in lifestyle resulting from relief of heartburn and other reflux-induced symptoms. Such relief is seldom achieved by traditional non-drug measures, which can also significantly impair lifestyle. In many patients with reflux disease, the effective relief of symptoms is a major aim. Oesophagitis, particularly when severe, carries a risk of developing peptic stricture or Barrett's oesophagus, but the risk factors associated with the development of these significant complications are not well identified. There is also no direct evidence that successful healing of oesophagitis by drug therapy is associated with prevention of local complications of oesophagitis, although many anecdotes regarding the resolution of peptic stricture by successful anti-reflux surgery support this possibility. Similarly, the linkage between development of Barrett's oesophagus and severe oesophagitis suggests that in some patients maintained healing of oesophagitis will prevent development or progression of Barrett's oesophagus. These considerations support the aim of healing of severe oesophagitis (i.e. more than patchy erosions), quite independently of the need to achieve effective symptom relief.

Beds

On-line intraoperative quantitation of regional myocardial perfusion during coronary artery bypass graft operations with myocardial contrast two-dimensional echocardiography.

We hypothesized that the success of coronary artery bypass graft operations could be assessed by means of on-line quantitative myocardial contrast echocardiography. Accordingly, myocardial contrast echocardiography was performed at baseline and after each placement of venous graft in 21 patients undergoing coronary artery bypass graft operations. Time-intensity plots were generated on-line with the use of a dedicated computer system, and areas under the curve were assessed for each injection. Successful on-line quantitation of myocardial contrast echocardiography data was performed in 17 patients; this allowed comparison before and after coronary artery bypass graft operations for 21 grafts, with agreement between expert visual analysis and quantitative data in 91% of these cases. Three distinct perfusion patterns were noted on myocardial contrast echocardiography: (1) reduced contrast effect before coronary artery bypass graft operations with improvement after coronary artery bypass graft operations (n = 11); (2) adequate contrast effect before coronary artery bypass graft operations with no change after coronary artery bypass graft operations (n = 9) (for patients in group 2, the mean percentage of coronary stenosis was less than the mean for patients in group 1-67% +/- 25% vs. 88% +/- 20%, p = 0.05); and (3) no contrast effect either before or after coronary artery bypass graft operations in one patient with previous infarction. One third of the time (34 of 95 injections), on-line quantitation was unsuccessful. Failure was related three times more often to problems associated with myocardial contrast echocardiography, such as attenuation and inadequate quality of bubbles, than to computer failure. Despite its limitations, on-line quantitative myocardial contrast echocardiography is feasible in patients undergoing coronary artery bypass graft operations and provides important objective information regarding the success of revascularization.

Aged

Sensory nerves of the intestines: role in control of pyloric region of dogs.

The canine pylorus is the target for a large array of extrinsic and intrinsic nerve-produced effects. Some of them have intermediate nicotinic synapses. In all cases observed so far the final nerve terminals mediating excitation are cholinergic, but those mediating inhibition are both adrenergic and non-adrenergic non-cholinergic. The role of the dense peptidergic innervation is unclear especially in view of the observation that this muscle and its nerves contain receptors to all of those studied (VIP, PHI, GAL, SP, NKA, NKB, CCK, and others. The pylorus is also the target of an important reflex initiated by acid in the duodenal lumen. Our preliminary work suggests that this reflex is initiated by acid induced release of 5HT from the EC cells to act on 5HT receptors on sensory nerves which activate the ascending chain of cholinergic nerves in the myenteric plexus. This same stimulus may also activate other vagal sensory nerves.

Animals

Twitch potentiation during fatiguing exercise in the elderly: the effects of training.

Twitch potentiation was studied during a fatigue paradigm involving intermittent maximum voluntary contractions (MVCs) of the tibialis anterior muscle in the elderly and in young adults. Resting twitch torques were similar between groups, but twitch potentiation was significantly greater (241% vs 166%) in the young; the recovery of the twitch after fatigue was similar between groups. Contraction time, time to peak torque and half-relaxation time were all significantly slower in the elderly. Following 12 weeks of resistance training in the elderly, there was no significant change in the twitch contractile properties at rest, but there was a significant main effect of training on the degree of twitch potentiation during the same fatigue protocol (peak potentiation 192% post-training vs 165% pretraining). These data suggest that the mechanism(s) responsible for twitch potentiation following MVCs may be influenced by both aging and training.

Aged

Provocation of transient lower esophageal sphincter relaxations by meals in patients with symptomatic gastroesophageal reflux.

The effect of a meal on the rate of transient lower esophageal sphincter (LES) relaxations and patterns of gastroesophageal reflux was investigated in 49 patients referred for evaluation of gastroesophageal reflux. Esophageal motility and pH were recorded concurrently before and after a standard meal. In the patients with symptomatic reflux, the meal induced a four- to sevenfold increase in the gastroesophageal reflux through two mechanisms: a four- to fivefold increase in the rate of transient LES relaxations and an increase in the proportion of transient LES relaxations accompanied by reflux from 47% to 68%. Overall the rate of reflux episodes that occurred by mechanisms other than transient LES relaxation did not increase significantly. An exception to these findings were those in six patients with chronically absent basal LES pressure in whom transient LES relaxations could not be scored. In these patients, reflux increased postprandially through mechanisms other than transient LES relaxation. These findings confirm the pivotal importance of transient LES relaxations in the pathogenesis of gastroesophageal reflux.

Esophagogastric Junction

A prospective genetic study of complete and partial hydatidiform moles.

Two hundred two hydatidiform moles were classified by pathologic features and ploidy into partial or complete moles. Further classification was made by using genetic polymorphism, the diagnosis being refined by deoxyribonucleic acid technology. Among 51 partial hydatidiform moles, 44 triploids, two tetraploids, and one diploid were identified. Informative triploid partial hydatidiform moles had one maternal and two paternal sets of chromosomes, the likely origin being dispermy. Among 149 complete hydatidiform moles, one was haploid, one was triploid, and 105 were shown to be diploid or androgenetic; 39 of these were proved homozygous, indicating duplication of the male genome, whereas heterozygous origin by dispermy was likely in 13. The locus-specific minisatellite deoxyribonucleic acid probes were particularly useful for the identification of heterozygous complete hydatidiform moles. None of the patients with partial hydatidiform moles had development of a gestational trophoblastic tumor. No difference was detected in the frequency of requirement for chemotherapy between patients with homozygous or heterozygous complete hydatidiform moles.

Blotting, Southern