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Biomedical subjects

J Dent

Publications and source records attributed to J Dent.

At least 235 records · Page 13Linked to original sources
PubMed1988

Intestinal 5-fluorouracil absorption: use of Ussing chambers to assess transport and metabolism.

We have employed an in vitro system to study transport and metabolism of organic molecules by gastrointestinal tissues. Such a system would aid in the evaluation of the potential for oral delivery of organic molecules. Transport and metabolism of 5-fluorouracil (5-FU) were studied using rabbit intestinal preparations. Unidirectional fluxes and metabolism were measured in vitro in Ussing chambers under short-circuit conditions. Results from these studies reveal that in ileum, proximal, and distal colon, steady-state fluxes of 5-FU (10 microM added to both bathing solutions) are established after 30 min and remain constant for at least 110 min. Transport of 5-FU under "sink" conditions with 10 microM 5-FU present in the mucosal or serosal bathing solution alone demonstrated similar rates of transport as under "nonsink" conditions. The concentration dependence of 5-FU fluxes indicates that the mucosal (m)-to-serosal (s) flux is composed of both a saturable and a linear component over the range of 1-100 microM in the ileum, whereas the s-to-m flux in the ileum and both fluxes in the colon are linear functions of concentration. Over the concentration range employed and the time course of these studies, 5-FU had no effect on the electrical properties of the ileum or colon. In the ileum, the m-to-s but not the s-to-m flux of 5-FU was reduced by (1) serosal ouabain (0.1 mM); (2) reduction of the bathing solution Na concentration; and (3) addition of uracil, thymine, thymidine, uridine, 2-deoxyuridine, or uridine-5'-monophosphate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

IIB von Willebrand's disease: pathogenetic and therapeutic studies.

Infusion of 1-deamino-(8-D-arginine)-vasopressin (DDAVP) into patients with IIB von Willebrand's disease (vWD) has been reported to induce thrombocytopenia. In some families with this disorder thrombocytopenia is present even in the resting state. We have investigated the basis of this chronic thrombocytopenia in one such patient by performing platelet recovery and survival studies. Increased platelet consumption was suggested by a decrease in platelet recovery (40.5%, normal 45%) and mean platelet survival (112 h, normal range 144-224 h). In addition, we have administered test infusions of DDAVP and observed the effect on bleeding time and platelet count. DDAVP caused a decrease in the median platelet count from 86 x 10(9)/l (range 30-221) to 60 x 10(9)/l (range 5-144), the individual decline in the nine subjects ranging from 12% to 84% compared to the pretreatment values. Formation of platelet aggregates was observed in all patients following DDAVP. The bleeding time was prolonged before DDAVP in all patients and lengthened further in two after the infusion. However, partial correction of the bleeding time was seen in three and normalization in one patient following DDAVP infusion. Two IIB vWD patients were treated with virus-inactivated cryoprecipitate (Ristofact). Infusion of cryoprecipitate was followed by rapid appearance of all but the largest vWF multimers in plasma and did not affect the platelet count. The bleeding time was normalized in one patient but remained prolonged in the other. In conclusion, in IIB vWD patients virus-inactivated cryoprecipitate is the treatment of choice in the case of bleeding. Infusion of DDAVP might be effective in a subset of IIB vWD patients that has yet to be characterized.

Bleeding Time↗
PubMed1988

Effect of general anaesthesia on transient lower oesophageal sphincter relaxations in the dog.

This report investigates the hypothesis that gastro-oesophageal flow is modulated by central nervous activity. The hypothesis was examined using the canine model in which gastro-oesophageal flow was stimulated by gastric insufflation of air at 80 ml/min and central nervous depression was produced with the anaesthetic agents thiopentone, nitrous oxide and halothane. Duplicate paired studies were performed in four dogs, either unsedated or anaesthetized. Gastro-oesophageal flow was assessed manometrically by a sleeve catheter assembly and by pH electrode. Gastric compliance was assessed by inflation of a thin-walled, plastic bag. Transient lower oesophageal sphincter relaxation, the dominant mechanism of retrograde trans-sphincter flow in unsedated animals, was abolished by general anaesthesia. Retrograde flow of gas across the lower oesophageal sphincter in anaesthetized animals eventually occurred, but only after massive gastric distension and elevation of gastric pressure to lower oesophageal sphincter pressure. The effects observed could not be explained by a direct action of anaesthetic on the lower oesophageal sphincter or on the gastric wall. It is proposed that general anaesthesia results in blockade of the neural pathway responsible for transient lower oesophageal sphincter relaxation by withdrawal of facilitative higher centre activity. The findings have implications for the use of sedation in experimental studies on factors which control gastro-oesophageal reflux, and clinical application to the risk of tracheal aspiration during general anaesthesia.

Anesthesia, General↗
PubMed1988

Extrinsic and intrinsic neural control of pyloric sphincter pressure in the dog.

1. In chloralose-urethane-anaesthetized dogs a manometric assembly was inserted via a gastrostomy to monitor pyloric pressure with a sleeve sensor. Antral and duodenal contractions were monitored with both manometric side holes and serosal strain gauges. 2. Subserosal silver wire electrodes were placed in the antrum 5 cm orad and the duodenum 3 cm aborad to the pylorus to facilitate field stimulation of intramural nerves. 3. The pylorus exerted spontaneous tone (10.8 +/- 4.8 mmHg) with phasic contractions occurring at a rate varying from 1-5 min-1 and, at times, with a superimposed higher frequency up to 15 min-1. Atropine (30 micrograms kg-1 I.V. and 10 micrograms I.A.) reduced and tetrodotoxin (50-100 micrograms I.A.) enhanced the phasic activity significantly. 4. Bilateral cervical vagal section had no consistent influence on pyloric motility. 5. Stimulation of the distal ends of the cervical vagal nerves at low frequencies (0.2-0.5 Hz, 1-3 ms, 20 V) induced phasic pyloric contractions, which were abolished by atropine or hexamethonium (10 mg kg-1 I.V. and 1 mg I.A.). Higher frequencies (greater than 0.7 Hz) of stimulation inhibited both phasic and tonic contractions and this inhibition was unaffected by atropine, hexamethonium, phentolamine (1.5 mg kg-1 I.V. and 100 micrograms I.A.) or propranolol (1 mg kg-1 I.V. and 100 micrograms I.A.). All neural responses were blocked by tetrodotoxin (50-100 micrograms I.A.). 6. Duodenal field stimulation (0.2-5 Hz, 0.5 ms, 40 V) induced strong phasic and tonic contractions in the pylorus. This excitation was blocked by atropine, hexamethonium, tetrodotoxin (50-100 micrograms I.A.) or duodenal transection orad to the stimulating electrodes. 7. Antral field stimulation (0.5-1 Hz, 0.5 ms, 40 V) completely abolished phasic activity in the pylorus and reduced tonic activity, regardless of whether the contractile activity was spontaneous or induced by neural stimulation. This inhibitory action was unaffected by atropine, hexamethonium or propranolol but was blocked by tetrodotoxin and antral transection aborad to the stimulating electrodes. Phentolamine attenuated the inhibitory effect of antral field stimulation on pyloric motility. 8. It is concluded that the distal canine pylorus exhibits myogenic tone and phasic activity which is modulated by extrinsic and intrinsic nerve pathways. Vagal nerves contain fibres, activated by different stimulus parameters which can either excite or inhibit pyloric activity. Activation of antral nerves inhibits pyloric activity, with both non-adrenergic, non-cholinergic and phentolamine-sensitive pathways contributing to this inhibitory response.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Stimulation of pyloric motility by intraduodenal dextrose in normal subjects.

Recent studies suggest that the pylorus may play an important role in the regulation of the gastric emptying of nutrient liquids in man. Dextrose solutions in the range 5-25 g/dl have been reported to empty from the human stomach at a constant caloric rate of 2.1 kcal/min. This study examined, in 12 healthy volunteers, the effects of intraduodenal dextrose on pyloric motility. Dextrose solutions, 5, 10, 15, and 25 gde/dl and saline solutions, 0.9 and 2.7 g/dl were infused into the duodenum at 4 ml/min for 10 minutes. Antral, pyloric, and duodenal motility were monitored with sideholes and a sleeve sensor positioned across the pylorus. Significant increases in the rate of isolated pyloric pressure waves and in basal pyloric pressure were seen with 15 and 25 g/dl dextrose (p less than 0.02) and 2.7 g/dl saline (p less than 0.05). The intensity and duration of the phasic and tonic pyloric motor responses to intraduodenal dextrose were dose dependent and correlated directly with the rate of calorie delivery (p less than 0.005 for each parameter). Intraduodenal delivery of dextrose at a rate in excess of 2.1 kcal/min stimulates both phasic and tonic pyloric contraction. These changes in pyloric motility may contribute to the close regulation of the emptying of dextrose from the stomach.

Adolescent↗
PubMed1988

Mechanisms of lower oesophageal sphincter incompetence in patients with symptomatic gastrooesophageal reflux.

Patterns of lower oesophageal sphincter (LOS) function associated with the onset of 644 reflux episodes were recorded and analysed in 67 patients referred for evaluation of gastro-oesophageal reflux (GOR). Patients were studied recumbent, for one hour before and four hours after a standard meal. Transient LOS relaxation was the most prevalent mechanism and overall accounted for 82% of reflux episodes. With increasing severity of oesophagitis, absent basal LOS pressure became a progressively more common mechanism, accounting for 23% of episodes in the patients with severe oesophagitis. Patients commonly exhibited more than one mechanism. The timing of most (69%) LOS relaxations associated with reflux was not compatible with triggering by swallowing. Prolonged transient LOS relaxations were associated with inhibition of oesophageal peristalsis suggesting that this response is produced by neural inhibition. This study suggests the primary importance of transient LOS relaxations as the cause of GOR across the spectrum of severity of reflux disease.

Esophagogastric Junction↗
PubMed1988

Antropyloroduodenal motor responses to intraduodenal lipid infusion in healthy volunteers.

The delivery of lipid to the duodenum has been shown to slow gastric emptying and to increase the resistance to gastric outflow. To investigate mechanisms responsible for these effects, we have recorded antropyloroduodenal motility in nine healthy volunteers during alternate intraduodenal infusions of normal saline and triglyceride emulsion (Intralipid 10%). During the lipid infusions there were reproducible, major changes in the patterns of motility. Pressure waves, apparently isolated to the pylorus, usually started within 10 min of initiation of the lipid infusion. After 20-25 min of lipid infusion these waves occurred at median rates of 2.4 and 2.8/min (1st and 2nd lipid infusions, respectively); these rates were significantly greater (P less than 0.05) than the median rates (all less than or equal to 0.4/min) observed during the equivalent period of the succeeding saline infusions. During 10 of 22 lipid infusions, isolated pyloric pressure waves were associated with sustained pyloric tone. Infusion of lipid into the duodenum suppressed antral pressure waves in all subjects and initiated brief periods of regular duodenal contractions during 11 of 22 infusions. These studies have demonstrated alterations of antropyloroduodenal motor patterns in response to changes in the duodenal luminal content. The effects on antral and pyloric motility are probably of importance in the regulation of transpyloric flow by nutrients in the duodenal lumen.

Adult↗
PubMed1988

Inhibitory opioid receptors in canine pylorus.

In 18 anesthetized dogs, antroduodenal and pyloric motility was monitored in vivo by a sleeve and perfused side-hole manometric assembly and by antral and duodenal serosal strain gauges. Close intra-arterial injection to the pylorus of dynorphin-(1-13) (Dyn) for kappa-receptors, [D-Pen2,5]enkephalin (DPen2,5-Enk) for delta-receptors, and [N-Me-Phe3-D-Pro4]morphiceptin (PL017) and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) for mu-receptors showed no excitatory effect in the pylorus. When pyloric motor activity was increased by duodenal field stimulation 3-5 cm aboaad from the pylorus, Dyn greater than DPen2,5-Enk greater than DAGO produced a dose-dependent inhibition of the pyloric motor activity. Naloxone (200 micrograms/kg iv and 20 micrograms ia) had no effect on the pyloric excitation due to duodenal field stimulation, but it reduced the inhibitory response of intra-arterially injected opioids. In addition, opioid binding ([3H]diprenorphine) in microsomal and mitochondrial fractions from the inner circular muscle ring of the pylorus showed a distribution similar to the neuronal marker [3H]saxitoxin but no correlation to the plasma membrane marker 5'-nucleotidase. These results suggest the existence of inhibitory opioid receptors (kappa- and delta-receptors) on excitatory neurons in the intestinal neuronal pathway, which activates the canine pylorus.

Animals↗
PubMed1988

Topography and measurement of pyloric pressure waves and tone in humans.

The topography of human pyloric pressure is ill defined, and previous studies of pyloric motility in humans have given conflicting results. A detailed profile of pyloric pressure has been recorded in seven healthy volunteers using a manometric assembly with 13 side holes spaced at 3-mm intervals on reverse aspect of a 3.5-cm long sleeve sensor. After a fasting control period of 40 min, recordings were made for 40 min during intraduodenal infusion of a lipid emulsion. Two major patterns of pressure waves were seen during the fasting control period, namely pressure waves confined to a narrow pyloric zone (isolated pyloric pressure waves) and pressure waves that were less localized and involved the antrum and/or duodenum. During lipid infusion the motility pattern was dominated by isolated pyloric pressure waves and localized pyloric tone. Ninety-two percent of the isolated pyloric pressure waves recorded by the sleeve were recorded by only one or two side holes, consistent with a phasically active zone less than 9 mm in length. Pyloric tone was confined to an even narrower zone and was most often recorded by only one side hole. When both tone and isolated pyloric pressure waves occurred together, they were recorded by the same side holes. By comparison with the side holes, the sleeve recorded 89% of isolated pyloric pressure waves and 98% of nonlocalized waves and recorded pyloric tone with a moderate sensitivity but high specificity. The technical challenge of recording localized pyloric contraction is considerable, and much of the conflict between previous studies of the human pylorus is explicable on methodological grounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effects of thallium poisoning on intellectual function.

A student of chemistry was treated for thallium poisoning. Seven months after his ingestion of thallium, intelligence tests were performed on the patient and his non-identical twin brother, who was of similar educational background. These indicated severe deterioration in intellectual function of the patient, particularly in memory and performance abilities. Tests 13 months after ingestion showed little general improvement.

Adult↗
PubMed1987

A method for continuous monitoring of upper esophageal sphincter pressure.

We tested a manometric assembly employing a sleeve sensor that is able to monitor anterior or posterior pressure in the human upper esophageal sphincter (UES) for prolonged intervals. When compared to rapid pull-through measurement of UES pressure obtained with conventional manometric assemblies, the sleeve sensor measured significantly lower UES pressures with less variability between subjects, thereby suggesting that the rapid pull-through maneuver stimulates the UES to contract. Concurrent recordings of UES pressure with a sleeve sensor and a side-hole sensor during a slow station pull-through yielded almost equal pressure values at the peak of the high-pressure zone (station zero), but the side-hole site recorded significantly lower pressures than the sleeve at stations 0.5 cm or more from the peak of the high-pressure zone. During 10 min of recording at station zero, the sleeve sensor recorded greater pressures than the side-hole sensor. This finding demonstrated the suceptibility of the side-hole sensor to axial movement relative to peak UES pressure. When stationary, both the sleeve sensor and the side-hole sensor recorded significantly lower UES pressure after 1-2 min of recording, again suggesting that movement of the recording assembly stimulates the UES to contract. Sleeve recordings of swallow-induced UES relaxations showed that UES relaxations induced by water swallows were slightly longer than those induced by dry swallows. Augmentations of UES pressure induced by balloon distension of the esophageal body were also recorded. We conclude that the sleeve sensor is a suitable method for investigating the normal physiology and pathophysiology of the UES in human subjects.

Adult↗
PubMed1987

Effect of sleep, spontaneous gastroesophageal reflux, and a meal on upper esophageal sphincter pressure in normal human volunteers.

Owing to the inherent difficulties of recording upper esophageal sphincter pressure, little is known about normal upper esophageal sphincter physiology. In this study we used a modified sleeve device to record upper esophageal sphincter pressure continuously in 8 normal volunteers. Intraesophageal pH and electroencephalogram activity were also recorded to document the occurrence of spontaneous gastroesophageal reflux and sleep. After an hour of baseline recording, the subjects ate a meal. Recording was then resumed for an additional 7 h during which period the subjects slept part of the time. The mean upper esophageal sphincter pressure was measured for each 10-min epoch. Electroencephalogram recordings were read blindly for the presence and stage of sleep. Periods of sleep were then correlated with the manometric tracings. Mean upper esophageal sphincter pressure during wakefulness, stage 1 sleep, and deeper sleep was 40 +/- 17 (SD), 20 +/- 17, and 8 +/- 3 mmHg, respectively. A significant change in upper esophageal sphincter pressure did not occur postprandially or during episodes of spontaneous gastroesophageal reflux. Upper esophageal sphincter pressure was observed to increase transiently with each inspiration during periods of restfulness and sleep, a response consistent with the hypothesis that one function of the upper esophageal sphincter is to exclude air from the esophagus during respiration. The demonstration that upper esophageal sphincter pressure falls markedly during sleep may have significance in that this diminishes the barrier to nocturnal regurgitation and potential aspiration.

Adult↗
PubMed1987

Measurement of upper esophageal sphincter pressure. Effect of acute emotional stress.

Recent studies suggest that resting upper esophageal sphincter pressure is more labile than previously thought, being augmented during rapid manometric pull-through and markedly decreased during sleep and anesthesia. The effect of acute emotional stress on resting upper esophageal sphincter pressure was evaluated in 13 normal subjects with a manometric sleeve assembly. Manometric sideholes were positioned in the pharynx and cervical and thoracic esophagus while the sleeve sensor straddled the upper esophageal sphincter. Subjects were stressed intermittently by 14-min periods of a dichotic listening task. As incentive, a financial reward was offered and made commensurate with performance. Alterations of heart rate, blood pressure, and skin conductance confirmed the effectiveness of the stressor. The overall mean upper esophageal sphincter pressure during control periods was 46.5 mmHg (SEM = 4.7). During stress there was a significant mean increase (11.8 +/- 2.9 mmHg; p = 0.002) in upper esophageal sphincter pressure from control levels, and the pressure increase during the first 2-min epoch of stress was 20.8 +/- 3.9 mmHg (p = 0.0003). Emotional stress causes significant elevation of upper esophageal pressure in normal subjects. This effect is likely to influence resting sphincter pressure measurements, particularly if measurement conditions are stressful to the subject.

Acute Disease↗
PubMed1987

Recent views on the pathogenesis of gastro-oesophageal reflux disease.

The pathogenesis of GORD depends on a mix of factors which vary amongst individual patients. The central issue in the pathogenesis of gastro-oesophageal reflux is understanding of the mechanisms that lead to reflux, since the effects of all other factors depend on this event. Consequently, new information and views about the mechanisms of gastro-oesophageal reflux have been presented in detail. This information suggests that defective lower oesophageal sphincter motility is the most important abnormality that underlies pathological gastro-oesophageal reflux. Two major forms of LOS dysfunction have been identified as responsible for pathological gastro-oesophageal reflux in the horizontal position: (1) an excessively frequent rate of occurrence of transient LOS relaxations; and (2) defective basal LOS tone. Both of these dysfunctions appear to arise from abnormal neural control of the LOS, probably by the central nervous system. The effect of these LOS dysfunctions on gastro-oesophageal competence is probably significantly influenced by non-sphincteric factors, the most important of these apparently being hiatus hernia. Though there is currently poor understanding about the ways in which hiatus hernia impairs gastro-oesophageal competence, measurement techniques have now advanced sufficiently to allow significant accrual of knowledge in this field. Once reflux has occurred, the efficiency of oesophageal acid clearance plays a major role in determining the impact of reflux on the oesophageal mucosa. Recent studies have shown that oesophageal acid clearance depends on both effective volume clearance and neutralization by saliva of residual acid in the oesophageal lumen. The efficiency of oesophageal volume clearance of both stimulated and real reflux has not been studied formally in GORD patients, but the high incidence of peristaltic dysfunction in reflux disease suggests that volume clearance will be defective in some patients. The limited information available about salivation in GORD patients suggests that salivary secretion is no different from that of age-matched controls, but that there is an age-dependent loss of the salivary response to oesophageal acidification. This impairment of salivary response may produce an age-dependent decline of the efficiency of oesophageal acid clearance. Unusually aggressive refluxate and impaired mucosal resistance to injury have been proposed as significant variables which contribute to pathogenesis of reflux disease. The evidence for these factors is circumstantial and scanty. Their importance has probably been overestimated.(ABSTRACT TRUNCATED AT 400 WORDS)

Abdomen↗
PubMed1987

In-vitro bacterial killing kinetics of ticarcillin/clavulanic acid.

An in-vitro model was developed to study the rates of killing by ticarcillin/clavulanic acid combinations of various beta-lactamase producing, ticarcillin resistant, logarithmic phase clinical isolates. Killing, defined as a 3 log reduction, was dependent on the organism, the concentration of clavulanic acid and the duration of exposure. For most isolates studied an optimum period of exposure to and concentration of clavulanic acid could be defined. Certain test strains showed optimum response to readily attainable in-vivo concentrations of clavulanic acid while other strains, although sensitive by MIC data showed a poor response. The clinical implications of this are discussed.

Bacteria↗
PubMed1987

Cognitive vulnerability to depression: an investigation of two hypotheses.

Two hypotheses concerning cognitive vulnerability to depression were examined. One suggested that there are persistent individual differences in cognitive processing related to neuroticism which predispose to depression. The other suggested that individuals in whom depressogenic processes are activated by mildly depressed mood are particularly vulnerable to becoming more seriously depressed. Compared to women who had never met Research Diagnostic Criteria for depressive disorders, women who had recovered from such disorders scored higher on measures of depression as an enduring characteristic; scored higher on measures of neuroticism; used more globally negative words, highly descriptive of depressed patients, to describe their personality; showed poorer recall of self-referred positive words, suggesting reduced activation of positive aspects of the self-schema; and in induced depressed mood showed better recall of self-referred global negative words, suggesting greater activation of related aspects of the self-schema. Results provided support for both hypotheses.

Adult↗
PubMed1987

Electrical control activity of the lower esophageal sphincter in unanesthetized opossums.

We recorded lower esophageal sphincter (LES) pressure and myoelectrical activity concurrently from the esophagus, LES, stomach, and proximal small intestine in unanesthetized opossums. LES electrical activity was characterized by almost continuous, spikelike oscillations at 15-40/min, which were accompanied by minicontractions 5-15 mmHg in amplitude. Basal LES pressure, however, did not depend on electrical oscillations. The LES exhibited cyclic changes in pressure and electrical activity synchronous with gastric contractions associated with the migrating myoelectric complex (MMC). During phase I, the LES pressure was stable and its electrical activity showed continuous low-amplitude (less than 0.3 mV) oscillations at a rate of 20 +/- 2 per min. During phases II and III of MMC-related gastric activity, the LES developed strong phasic contractions, while the electrical oscillations grouped into clusters with an increased rate (32 +/- 1 per min) and amplitude (0.4-0.8 mV), each cluster corresponding to a phasic contraction. Feeding, pentobarbital, and cholinergic blockade abolished MMC-related LES activity and resulted in a steady rate of LES electrical oscillations. LES relaxation induced by swallows or esophageal balloon distention abolished the LES electrical oscillations. Increases in LES pressure induced by pharmacological and hormonal stimulation correlated with concurrent increases in the rate of electrical oscillations. We conclude that the opossum LES has a unique pattern of electrical activity that differs from the electrical activity recorded from smooth muscle elsewhere in the gastrointestinal tract. This electrical activity is a form of control wave associated with a minicontraction. Phasic LES contractions during the intestinal MMC cycle may result from an increase in the rate and amplitude of the LES electrical control waves and fusion of minicontractions.

Anesthesia↗