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Biomedical subjects

J Dent

Publications and source records attributed to J Dent.

At least 217 records · Page 12Linked to original sources

Neural reflex of the canine pylorus to intraduodenal acid infusion.

In 29 chloralose-urethane anesthetized dogs, a manometric assembly was inserted through a gastrostomy to monitor pressure of the pyloric region with a sleeve sensor. Antral and duodenal contractions were monitored with both manometric sideholes and serosal strain gauges. An additional tube channel allowed intraduodenal infusions 1-2 cm aborad from the pylorus. Intraluminal infusion of hydrochloric acid (0.1 N, 0.92 ml/min, for 2 min) reproducibly caused activation of motor activity in the pyloric region and peristaltic duodenal activity. Proximal duodenal activity probably contributed to the total phasic response recorded in the pylorus region. Excitatory responses could also be elicited by infusion of phenyl-biguanide (stimulant of sensory nerve endings), but not by control infusions with diluent (Krebs' buffer or saline). The motor response of the pyloric region to intraduodenal acid was blocked by intraduodenal application of 2% xylocaine. Atropine (30 micrograms/kg i.v. and 100 micrograms i.a.) or hexamethonium (10 mg/kg and 1 mg i.a.) markedly reduced or blocked the acid-induced pyloric motor response of this region but propranolol (1.0 mg/kg i.v. and 100 micrograms i.a.), phentolamine (1.5 mg/kg i.v. and 100 micrograms i.a.), or naloxone (200 micrograms/kg and 20 micrograms i.a.) had no effect. We believe these observations show the existence of a reflex from the duodenum to the pylorus in response to intraluminal stimuli mediated by a chain of cholinergic nerves. In the dog, endogenous opioid peptides do not contribute to the excitatory reflex pathway activated by intraduodenal acid or phenyl-biguanide. As intraluminal acid in the duodenum activates this reflex, it may play a role in the physiologic and pathophysiologic role of gastric emptying in this species.

Anesthesia, Local↗

Pyloric motor response to intraduodenal dextrose involves muscarinic mechanisms.

The delivery of dextrose solutions to the duodenum is associated with the stimulation of phasic and tonic pyloric contraction. In this study, the effects of intravenous atropine on the antropyloroduodenal motor responses to intraduodenal infusions of 25% dextrose were assessed in 10 normal volunteers. Antropyloroduodenal pressures were recorded with a manometric assembly incorporating a sleeve sensor spanning the pylorus, and sideholes in the antrum and duodenum. In each experiment, three intraduodenal infusions of 25% dextrose were given at a rate of 4 ml/min, for a median duration of 19 min (range 17-20). During the second dextrose infusion, intravenous atropine was given as a bolus (15 micrograms/kg) followed by an infusion (4 micrograms/kg.min), which was continued until the end of each experiment. Before atropine was given, the pyloric motor response to the second dextrose infusion was not significantly different from the response to the first infusion, but after administration of atropine there was a rapid decrease in the rate of isolated pyloric pressure waves, from 0.8 to 0.1 per minute (p less than 0.05). The isolated pyloric pressure wave response to the third dextrose infusion was completely blocked, and there was a much smaller maximum increase in basal pyloric pressure compared with the first infusion (p less than 0.01). This study indicates that intraduodenal dextrose reproducibly stimulates isolated pyloric pressure waves and increases basal pyloric pressure by mechanisms that involve muscarinic receptors.

Adult↗

Influence of indomethacin amphoteric gel on gastric ulcerogenicity and absorption of indomethacin in rats.

Indomethacin is a potent and efficacious antiinflammatory agent. However, a limiting side effect is its ability to cause gastric ulceration. This study was designed to investigate the effects of an amphoteric gel on the gastric ulcerogenicity and pharmacokinetics of indomethacin. Oral administration (5 mg/kg) in a suspension and a gel formulation were compared to an intravenous (iv) formulation of indomethacin in rats. The iv formulation administered to rats produced large severe ulcers in some rats but not in others. In contrast, the oral suspension produced small ulcers in all rats. The difference in toxicities is attributed to a centrally mediated action as a result of high plasma levels of indomethacin following iv administration, compared to locally mediated action with the suspension, resulting from local high concentrations of indomethacin on the apical epithelial surface because of the presence of indomethacin crystals. Oral administration of the gel formulation did not result in any gastric ulceration and improved the bioavailability of indomethacin to 115.5%, compared with 68.2% for the suspension. The reduced gastrointestinal toxicity of indomethacin in the gel was attributed to the gel's ability to dissolve indomethacin, preventing the localized high concentration observed with the suspension and possibly providing a gastric protectant phospholipid. The gel formulation doubled the oral bioavailability and the tmax of indomethacin compared to the suspension but did not affect the half-life. The results indicate that the local irritant effect of indomethacin, in rats, can be reduced by appropriate formulation design and suggest that the ulcerogenicity index for indomethacin can be improved by the use of an amphoteric gel formulation.

Administration, Oral↗

The role of low-dose methotrexate and folinic acid in gestational trophoblastic tumours (GTT).

Between 1964 and 1986, 487 patients with gestational trophoblastic tumour (GTT) were treated with methotrexate and folinic acid. The patients comprise two groups: between 1964 and 1974, 126 patients were treated but were not systematically stratified using a prognostic score before the start of treatment. These patients formed part of the 317 women who were analysed to identify a number of prognostic variables (Bagshawe 1976). Retrospective analysis of these 126 patients using these prognostic factors showed that in the true low-risk group 85/88 (96%) are alive while 20/22 (91%) of the medium-risk group and only 5/16 (31%) of the high-risk group are alive. Overall the survival was 110/126 (87%) with a minimum follow-up of 14 years. From 1974 all patients were stratified on admission into prognostic groups. Of the true low-risk patients 347/348 survived (99.7%); 13 patients were underscored and treated as low risk when they should have been treated as medium risk, 12 (92%) of these are alive, but nine (69%) needed to change treatment because of drug resistance. While the overall survival in the 1974-1986 group was 359/361 (99%) with a minimum follow-up of 16 months, the survival in all patients (1964-1986) was 469/487 (96%). Although the survival in these patients is excellent it should be noted that 69/348 (20%) low-risk patients had to change treatment because of the development of drug resistance, and a further 23 (6%) needed to change treatment because of drug-induced toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Failure of transient lower oesophageal sphincter relaxation in response to gastric distension in patients with achalasia: evidence for neural mediation of transient lower oesophageal sphincter relaxations.

Transient lower oesophageal sphincter relaxation (LOSR) is the major mechanism underlying gastro-oesophageal reflux. The mediation and control of LOSRs are incompletely understood but evidence suggests a neural inhibitory mechanism. In this study we have evaluated the effect of gastric distension on LOS function in 16 patients with untreated idiopathic achalasia and compared it with that in 10 healthy controls. With the subjects sitting, the stomach was distended with a liquid mixture that generated 750 ml CO2. Oesophageal pH and motility were monitored for 10 minutes before and after distension. In normal controls, gastric distension induced a four-fold increase in the rate of LOSRs and gas reflux episodes (as evidenced by oesophageal common cavities), whereas this response was absent in the achalasia patients. Basal LOS pressure did not change in either group. These findings are consistent with the notion that transient LOSRs induced by gastric distension are neurally mediated, probably by the same inhibitory nerves that govern swallow mediated LOS relaxation.

Adolescent↗

Effect of cisapride on postprandial gastro-oesophageal reflux.

We studied the effect of cisapride on oesophageal motor function and postprandial gastro-oesophageal reflux in a randomised, double blind, placebo controlled crossover study. In 16 patients with symptomatic gastro-oesophageal reflux, cisapride 10 mg orally and placebo were studied on separate days according to identical protocols. Cisapride and placebo were given 30 minutes before a standard meal. Each study day was preceded by corresponding three day oral loading of cisapride (10 mg tds) or placebo. Lower oesophageal sphincter pressure, oesophageal body motility and oesophageal pH were monitored for 30 minutes before and three hours after the meal. Plasma cisapride concentrations were measured before and after dosing on both study days. With cisapride treatment, the plasma cisapride levels ranged from 48.1 (5.0) to 75.9 (6.9) ng/ml. Plasma levels were undetectable during placebo treatment. Cisapride enhanced acid clearance but had no significant effect on the duration of acid exposure, the rate of reflux episodes, the pattern of lower oesophageal sphincter pressure associated with the reflux episodes, basal lower oesophageal sphincter pressure or oesophageal peristalsis. These findings do not suggest a major role for cisapride, at the dosage tested, for the control of troublesome postprandial gastro-oesophageal reflux.

Adult↗

Inhibitory function of VIP-PHI and galanin in canine pylorus.

Contractions of canine pylorus and adjacent muscles were recorded with antral and duodenal strain gauges and a Dent sleeve manometric assembly with additional side holes in the pylorus. In vivo, vasoactive intestinal polypeptide (VIP) and peptide histamine isoleucine (PHI) given through the gastroepiploic artery inhibited both spontaneous and acetylcholine-induced pyloric contractions, before and after neural blockade with tetrodotoxin. Galanin inhibited only nerve-stimulated contractions. VIP greater than PHI much greater than galanin inhibited pyloric motor activity initiated by field stimulation of duodenal intramural nerves or intraduodenal infusion of 0.1 N HCl. In vitro, forskolin or field stimulation of nerves inhibited contractions of the pyloric muscle induced by various agonists but VIP-PHI failed to inhibit these contractions on two-thirds of the strips. The in vivo results suggest that VIP (or PHI) may be an inhibitory mediator in the pylorus acting directly on smooth muscle. Galanin may inhibit neural excitatory pathways in the pylorus. However, the structures on which VIP and PHI act in vivo may have become nonfunctional in vitro and other mediators account for the neural inhibition observed in isolated strips.

Acetylcholine↗

Weekly alternating etoposide, methotrexate, and actinomycin/vincristine and cyclophosphamide chemotherapy for the treatment of CNS metastases of choriocarcinoma.

Twenty-five patients with CNS metastases of choriocarcinoma were treated with a regimen incorporating etoposide, methotrexate, and actinomycin (EMA) alternating weekly with vincristine and cyclophosphamide (CO). The dose of methotrexate was increased to 1 g/m2. Eighteen patients presented with CNS metastases, or developed them on inappropriate treatment started elsewhere. Following EMA/CO chemotherapy, three patients died within the first 3 weeks, one is alive with active disease, one died with drug resistance, and 13 (72%) patients are surviving disease-free. Two of seven patients (29%) who developed CNS metastases on treatment with EMA/CO or relapsed after EMA/CO are disease-free after additional chemotherapy and surgery. The contribution toward survival of the craniotomy in six of 18 patients treated initially or early with EMA/CO remains unclear, but was crucial to those patients with drug resistance.

Adult↗

A scanning electron micrographical study of root surfaces and subgingival bacteria after hand and ultrasonic instrumentation.

The effects of hand and ultrasonic instrumentation on root surface topography and subgingival plaque were studied. One approximal subgingival root surface on each of two single rooted teeth of six patients was root planed. The opposing proximal surfaces were not treated and served as controls. On each patient, the two test surfaces were randomly treated by hand or ultrasonic instrumentation (Cavitron) until clinically smooth. The teeth were extracted, divided into mesial and distal sides, and processed for scanning electron microscopy (SEM). The observations were restricted to an area 2 mm by 3 mm just coronal to the plaque-free zone. The root surfaces were scanned by SEM, both at low (x 100) and at higher magnifications (x 5000). At low power, a photomontage was produced of the surface area of the test teeth. At low magnifications (x 100, x 500), the topography resulting from hand instrumentation appeared smooth with parallel scratches compared to scaly but flat surfaces with occasional deep gouges with the ultrasonic method. At high magnifications (x 5000), tooth surfaces were similar in topography when instrumented by either hand or ultrasonic methods. Root surfaces were covered in some areas by a fibrillar-like membrane that resembled fibrin. Individual bacteria were found on the surfaces of this material. On other areas not covered by this membrane, bacterial plaque was only observed when tooth surfaces had not been contacted by either hand or ultrasonic instrumentation.

Aged↗

Evaluation of omeprazole in reflux oesophagitis.

In patients with reflux disease, pH monitoring has shown that omeprazole virtually eliminates oesophageal exposure to a pH of less than 4. Motility studies concurrent with pH monitoring have indicated that reflux continues on omeprazole, its effect on acid exposure being entirely dependent on elevation of gastric pH. Omeprazole and placebo have been compared in 64 patients with erosive or ulcerative oesophagitis; the 4-week healing rates were 81% with omeprazole, 20 mg or 40 mg daily, and 6% with placebo. The efficacies of omeprazole at doses of 20 mg and 40 mg daily, were then compared in 164 patients. At 4 weeks, oesophagitis was healed in 70% and 82% of patients for the 20 mg and 40 mg doses respectively (p = 0.05). Eight-week healing rates (79% for 20 mg and 85% for 40 mg) did not differ significantly. Symptom response was excellent for both doses. Relapse of oesophagitis was determined over 6 months for patients healed with omeprazole. Relapse was shown to occur in 88 of 107 patients by 6 months. Omeprazole is a highly effective treatment for erosive/ulcerative peptic oesophagitis, 40 mg daily being marginally superior to 20 mg. Relapse is almost inevitable within 6 months of cessation of therapy.

Dose-Response Relationship, Drug↗

Approaches to oesophageal columnar metaplasia (Barrett's oesophagus).

The oesophageal squamous mucosal ulceration caused by peptic oesophagitis is followed by healing, with metaplastic columnar mucosa in around 12% of patients. The major significance of this condition, oesophageal columnar metaplasia (OCM), is the relatively high risk that it has for development of oesophageal adenocarcinoma. Fibreoptic endoscopy with multiple mucosal biopsies is the only effective method for detection and evaluation of OCM. Peptic oesophagitis merits treatment in its own right in patients with OCM. There are, however, no clear indications that once OCM has developed, successful healing of oesophagitis by medical or surgical therapies has any impact on the risk of malignancy. Management, therefore, hinges on effective treatment of severe oesophagitis before OCM develops, and surveillance for adenocarcinoma in OCM patients in whom oesophagectomy is considered a therapeutic option. Currently, the most effective screening method is to examine for dysplasia multiple closely spaced biopsy specimens from the columnar lined segment. Mild to moderate dysplasia probably warrants yearly endoscopy and multiple specimens. Severe dysplasia indicates a very high risk for invasive adenocarcinoma. In such patients, oesophagectomy should be seriously considered. Currently, there is a lively interest in research into more sensitive and cost-effective methods for screening for adenocarcinoma.

Adenocarcinoma↗

Factors that influence induction of gastroesophageal reflux in normal human subjects.

Findings from recent studies indicate that transient relaxation of the lower esophageal sphincter (LES) is an important contributory mechanism to spontaneous episodes of gastroesophageal reflux (GER) in normal subjects as well as in patients with reflux esophagitis. Our study aim was to evaluate the interrelationship between reduction of LES pressure and elevation of intraabdominal pressure in the induction of GER in healthy subjects. Seven volunteers were studied supine after gastric loading with 0.1 N HCl. A pH probe recorded acid GER. Leg raising (LR) or abdominal compression (AC) were used as stress maneuvers to increase intraabdominal pressure, either alone or in combination with stimuli that concurrently lowered LES pressure, namely multiple rapid swallows (RS) or intraesophageal balloon distention (BD). Each individual stimulus and stimulus combination was tested three times, giving a total of 24 test maneuvers per subject. The test maneuvers elicited 2-12 GERs in each subject. The GER incidence for single maneuvers was: AC, 0%; LR, 0%; RS, 19%; and BD, 24%. LR in combination with RS or BD did not increase the incidence of GER above that induced by RS or BD alone. In contrast, AC concurrent with RS and BD increased the incidence of GER to 52% and 81%, respectively. For all test conditions, a prerequisite for the occurrence of GER was a fall in LES pressure to a minimal value of 3 mm Hg or less. GER never occurred when LES pressure was greater than or equal to 4 mm Hg, even during intervals of increased intraabdominal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Healing and relapse of severe peptic esophagitis after treatment with omeprazole.

We have studied the response of erosive or ulcerative esophagitis to treatment with omeprazole and its subsequent relapse on cessation of therapy in 196 patients. In the first phase of the study omeprazole (20 or 40 mg daily) was compared with placebo in 64 patients. After 4 wk there was endoscopic healing in 81% (25 of 31) of omeprazole-treated patients and in only 6% (2 of 32) of placebo-treated patients. Endoscopic healing of esophagitis was accompanied by symptom relief and histologic healing of ulceration. In the second (dose finding) phase a further 132 patients were randomized to omeprazole (20 or 40 mg daily) and endoscopic healing was assessed. In patients with the mildest grade of ulcerative esophagitis (grade 2), healing occurred at 4 wk in 87% receiving 20 mg and in 97% receiving 40 mg. In patients with grade 3 esophagitis, 67% (20 mg) and 88% (40 mg) were healed. Less than half the patients with grade 4 esophagitis (Barrett's ulcers or confluent ulceration) healed with either 20 mg (48%) or 40 mg (44%). Regression analysis in the 164 omeprazole-treated patients showed no evidence that healing was influenced by factors other than severity of esophagitis at entry and omeprazole dose. In phase 3 of the study the rate of endoscopic relapse was determined in 107 endoscopically healed patients after stopping omeprazole. Erosive or ulcerative esophagitis recurred in 88 of 107 (82%) by 6 mo. Neither initial dose, grade of esophagitis, nor smoking was shown to influence relapse rate. Omeprazole is a highly effective treatment for peptic esophagitis. The 40-mg/day dosage produces endoscopic healing slightly more quickly than the 20-mg/day dosage, and the initial endoscopic gradings are of prognostic value. Relapse occurs rapidly when treatment is stopped.

Adult↗

Upper esophageal sphincter function during deglutition.

Upper esophageal sphincter function was investigated during swallows of graded volumes in 8 normal volunteers. Concurrent recordings of video-fluoroscopic and manometric studies were obtained and correlated with each other by means of a videotimer. Maximal upper esophageal sphincter (UES) pressure was typically located 1.5 cm distal to the air-tissue interface between the hypopharynx and the proximal margin of the sphincter. The region in which UES pressure was greater than or equal to 50% maximal averaged 1.0 cm in length. Thus, the physiologic high-pressure zone of the UES corresponds in size and location to that of the cricopharyngeus muscle. Fluoroscopic analysis of sphincter movement indicated that the sphincter high-pressure zone moved 2.0-2.5 cm orally during swallowing and that the magnitude of the orad movement was directly related to the volume of barium swallowed. The maximal anterior-posterior diameter of sphincter opening during a swallow ranged from 0.9 to 1.5 cm and was also directly related to the volume swallowed. The intervals of UES opening and relaxation increased significantly with increasing bolus volume; the duration of UES relaxation ranged from a mean of 0.37 s for dry swallows to 0.65 s for 20-ml swallows. Thus, the dynamics of UES function during deglutition are dependent upon the volume of the swallowed bolus. Larger bolus volumes are accommodated by both an increased diameter of sphincter opening and by prolongation of the interval of sphincter relaxation. Analysis of the timing of other reference points within the pharyngeal swallow sequence indicated that as the manometric interval of UES relaxation increased, the period of laryngeal elevation was prolonged, the UES relaxed earlier and contracted later, and the interval between the onset of laryngeal elevation and hypopharyngeal contraction increased.

Adolescent↗

Motor activity of the gastric antrum, pylorus, and duodenum under fasted conditions and after a liquid meal.

Because the mechanisms that control the movement of food and digestive juices across the human pylorus are not completely understood, the aim of this study was to document the normal patterns of pressure activity in the antrum, pylorus, and duodenum and the associated pH changes in 9 healthy volunteers. Studies were carried out under fasting conditions and after ingestion of 300 ml of chocolate milk, using a unique 11-channel intraluminal probe that incorporated a sleeve sensor positioned across the pylorus and pH electrodes situated in the terminal antrum and proximal duodenum. The most common motor pattern recorded under fasting conditions consisted of regular coordinated contractions, most of which (a) involved the antrum and duodenum, (b) showed evidence of propagation through two or more adjacent channels, and (c) were associated with transient reductions in duodenal pH and transient elevations in antral pH. Ingestion of milk changed the motor pattern to one that was composed of pressure waves, which were confined to the pylorus with few or no pressure waves in the terminal antrum or proximal duodenum. Isolated pyloric pressure waves were gradually replaced by propagated antroduodenal contractions, which eventually occurred at a regular frequency that was higher than that observed under fasting conditions. After ingestion of milk, only the coordinated contractions were associated with transient reductions in duodenal pH. Isolated pyloric pressure waves were also observed under fasting conditions just before or just after phase III of the migrating motor complex, and 17% of these were accompanied by episodes of duodenal acidification.

Adult↗

Relationship of the motor activity of the antrum, pylorus, and duodenum to gastric emptying of a solid-liquid mixed meal.

The postprandial motor activity of the antrum, pylorus, and duodenum in 15 healthy volunteers was compared with the profiles of emptying of the solid and liquid components of a meal. The liquid component of the meal emptied rapidly in an exponential manner, whereas the solid remained in the fundus of the stomach until approximately 80% of the liquid had emptied and then emptied in a linear manner. The onset of solid emptying was associated with an increase in the rate of occurrence of antral pressure waves (p less than 0.05), and the half-time for solid emptying (t1/2 - lag period) was inversely correlated (p less than 0.05) with the rate of coordinated contractions involving the antrum. The substitution of 25% dextrose in normal saline as the liquid component of the meal increased the half-time for liquid emptying from a median of 8 to 40 min (p less than 0.01), increased the lag period for solid emptying from 40 to 87 min (p less than 0.01), and increased the rate of occurrence of isolated pyloric pressure waves during the solid lag phase from 7 to 58/h (p less than 0.05), but did not affect the slope of solid emptying or the rate of coordinated contractions involving the antrum during the solid emptying period.

Adolescent↗