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Biomedical subjects

E J Post

Publications and source records attributed to E J Post.

13 recordsLinked to original sources

Airway protection following simulated gastro-oesophageal reflux in sedated and sleeping neonatal piglets during active sleep.

1. In infants, promethazine has been implicated in the pathogenesis of sleep apnoea, apparent life threatening events (ALTE) and the Sudden Infant Death syndrome (SIDS). The aim of the present study was to investigate, in a neonatal animal, the effects of a commonly used promethazine-containing medication on airway protective mechanisms and cardiorespiratory reflexes following simulated gastro-oesophageal reflux (GER) to different levels in the oesophagus and pharynx. 2. Physiological and radiographic recordings were made in 21 naturally sleeping (controls) and 21 sedated (1.5 mg/kg, p.o., promethazine) piglets. On 3 consecutive days physiological recordings were made in all piglets during active sleep. Gastro-oesophageal reflux was simulated by the injection of boluses of 0.5 mL HCl, pH 2 or 3, or NaCl (0.9%) at 37 degrees C into the pharynx, upper or lower oesophagus. 3. In healthy neonatal piglets, minimal sedation with promethazine, which did not affect behaviour during wakefulness, revealed previously unreported findings during active sleep. 4. The most significant effects were observed following simulated GER to the pharynx, with no effect observed in the lower oesophagus. In sedated piglets, compared with naturally sleeping piglets, there was a significant reduction in swallowing (P < 0.01), delayed radiological clearance of fluid (P < 0.05), a reduction in breathing rate, oxygen saturation and heart rate and an increase in apnoea. 5. These findings are consistent with a low dose of promethazine producing a significant attenuation of airway protective mechanisms and, thus, stimulation of the laryngeal chemoreflex. The results suggest a mechanism for the association observed between promethazine use and the occurrence of ALTE and SIDS. The results support continued caution and suggest the need for greater regulation of promethazine-containing medications in infants.

Animals↗

Effects of promethazine on porcine gastroduodenal function: a sonographic study.

This sonographic study was aimed at examining the effect of sedation with promethazine (1.5 mg x kg(-1)), on gastroduodenal function in neonatal piglets. On 3 consecutive days, observations of gastroduodenal motility during the first 3 postprandial h were made in 13 animals (3 to 5 days old; 7 sleeping naturally and 6 sedated 2 h prior to feeding). Promethazine significantly reduced both the closures per min of the terminal part of the pyloric antrum and pyloric canal and the percentage of gastric contractions that were followed by closure of the terminal pyloric antrum and canal. Such actions of promethazine on motility of the gastroduodenal junction could lead to a delay in gastric emptying of ingesta with a consequent increased risk of reflux of gastric contents into the esophagus. Because gastroesophageal reflux has been associated with the pathogenesis of sudden infant death syndrome (SIDS), care should be taken if promethazine is to be used as a sedative in neonates.

Animals↗

Sedation with promethazine profoundly affects spontaneous airway protection in sleeping neonatal piglets.

1. Phenothiazine use in infants has been implicated in apparent life-threatening events, sleep apnoea and Sudden Infant Death Syndrome. 2. The aim of this study was to investigate the cumulative effects of a commonly used antihistamine medication containing promethazine on airway protective mechanisms and cardiorespiratory responses in 42 healthy neonatal piglets (21 naturally sleeping, 21 sedated sleeping). 3. Sedated piglets were given 1.5 mg/kg, p.o., promethazine 2 h prior to each recording session. Control animals slept naturally with no sedative given. On three consecutive days in all piglets, physiological recordings were made during sleep; on at least one of these days, simultaneous physiological and radiological observations were made. 4. Following sedation, sleep time and time in active sleep were increased significantly (P < 0.01). The spontaneous occurrence of swallowing, arousal, body movement, gastrooesophageal reflux and apnoea was compared between naturally and sedated sleeping piglets. Sedation with promethazine significantly decreased the spontaneous occurrence of swallowing (P < 0.05) and arousal (P < 0.05) and increased the occurrence of both central (P < 0.05) and obstructive sleep apnoea (P < 0.0001). 5. By the third day, a cumulative effect of promethazine was seen; the rate of swallowing and body movement significantly decreased (P < 0.01). 6. In summary, a low dose of promethazine profoundly altered sleep characteristics, airway protective mechanisms and cardiorespiratory responses in normal healthy sleeping piglets. Continued use of promethazine over several days may attenuate airway protective mechanisms to a potentially life-threatening degree. Our findings support continued caution in the use of promethazine-containing medications for the sedation of infants.

Animals↗

Sonographic observations of the gastroduodenal junction in neonatal piglets.

Knowledge of the function of the gastroduodenal junction is important, as changes in its motility are associated with gastrointestinal disorders. Sonographic observations were made of the stomach and duodenum of 19 neonatal piglets, 2-6 d of age. Contractions of the stomach and duodenum were identified clearly; the overall rate of gastric contractions was about 4 min-1. The percentage of contractions in which there was a closure of the terminal pyloric antrum and pyloric canal varied, being 57.2% +/- 4.6% in the first postprandial hour and 43.1% +/- 3.0% in the third. Antegrade flow of digesta principally occurred preceding a closure of the pyloric antrum and canal. During contractions of the pyloric antrum, the torus pyloricus moved caudally to fill the lumen of the pyloric canal. Our sonographic method provided a noninvasive technique for studying the form and function of gastroduodenal motility in the neonate, suitable for investigating factors that alter gastric emptying.

Animals↗

Physiological studies of gastro-oesophageal reflux and airway protective responses in the young animal and human infant.

1. The mechanisms that underlie the Sudden Infant Death Syndrome (SIDS) must explain its two unique features; age at death and death during apparent sleep. 2. The occurrence of gastro-oesophageal reflux (GOR) during active sleep in infants presenting with apparent life threatening episodes (ALTE) and their similar age distribution to SIDS infants, suggested that reflux could be a cause of asphyxia. 3. Sleep related GOR was found to be a physiological and not a pathological event in normal, healthy term infants. 4. In healthy term infants, those infants that were formula-fed (who have a higher incidence of SIDS) had significantly longer oesophageal clearance times for acid reflux and significantly more active sleep compared with breast fed infants. 5. In very preterm infants (who are at increased risk for SIDS), both the frequency and duration of reflux during active sleep was significantly less at term equivalent age compared with healthy term infants, suggesting additional factors must operate to promote an ALTE. 6. One mechanism which may explain the pathogenesis of GOR could be that the reflux reaches the level of the pharynx and this, in turn, stimulates laryngeal receptors to produce apnoea. 7. Simulated reflux to the level of the pharynx in the sleeping piglet evoked airway protective responses, namely swallow, arousal and occasionally expectoration, but neither apnoea nor oxygen desaturation. 8. In the same piglets treated with pentobarbitone sodium, swallowing was impaired and arousal depressed. Simulated reflux to the pharynx produced significant apnoea and oxygen desaturation and death in two of five piglets.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanisms of airway protection after pharyngeal fluid infusion in healthy sleeping piglets.

The airway protective mechanisms evoked after infusion of fluids into the pharynx were examined in the intact and healthy newborn piglet during sleep. Thirteen healthy normothermic piglets (3-6 days of age) were examined on 4 consecutive days during sleep. The fluids infused (0.05-1.5 ml) were 0.9% saline, distilled water, and HCl (pH 3 and pH 2). Respiratory rate, heart rate, oxygen saturation (SaO2), swallowing, and arousal were compared pre- and postinfusion during active (AS) and quiet sleep (QS) for each test fluid. The most common response in AS and QS was swallowing (90%) and then arousal (24%); however, no apnea occurred, and respiratory rate and SaO2 were always maintained. A significant difference occurred between HCl infusions of pH 2 and pH 3; at pH 2, the frequency of swallows and latency to the first swallow were reduced (P < 0.05) and the frequency of arousal was reduced in AS compared with that in QS (P < 0.01). Airway protection after pharyngeal fluid stimulation is achieved primarily by swallowing and arousal, without any effect on respiratory rate and SaO2. Attenuation of protective mechanisms occurred, however, when the infusate was at pH 2.

Animals↗

A method for simultaneous physiological and radiographic recordings from sleeping neonatal piglets.

A healthy neonatal piglet model was developed to investigate the effects of simulated gastro-esophageal reflux (GER) on airway protective mechanisms in different sleep states. Piglets were chosen for the model because there are similarities in esophageal morphology, development of the cardiorespiratory system and sleep-wakefulness cycle between the piglet and the human infant. Unanesthetized piglets were instrumented and trained to sleep in a radiolucent, temperature-controlled box. Physiologic recordings of sleep (electroencephalogram, 'ear-o-gram', behavioral observations), cardiorespiratory function (end-tidal CO2, O2 saturation, heart rate, respiratory movements), swallowing (pharyngeal or esophageal pressures) and GER (signaled by a fall in esophageal pH) were displayed and stored on a computer. An image intensifier was used for radiographic observations. The outputs from the computer and image intensifier were synchronized and recorded on videotape. The method enabled simultaneous physiologic and radiographic observations to be made during the simulation of GER by the injection of normal NaCl, distilled water or HCl (pH 2 and 3) into either the pharynx or different sites in the esophagus. The piglet model appears to accurately reflect the normal physiologic responses of the healthy sleeping neonate.

Airway Obstruction↗

Effects of malonic, maleic, citric and caffeic acids on the motility of human sperm and penetration of cervical mucus.

The spermicidal effect of four organic acids (malonic, maleic, citric and caffeic acids) was evaluated by adding the acids to sperm, and by observing sperm survival and penetration following addition of these acids to human cervical mucus. Direct addition of 0.1% malonic, maleic and citric acid rendered the sperm immotile by a reduction of pH. In capillaries filled with cervical mucus, the incorporation of 0.01% maleic, malonic and citric acids was sufficient to reduce sperm penetration, and at 0.1%, penetration was completely abolished. Thus, malonic, and maleic and citric acids show promise as cervical or vaginal contraceptives. Caffeic acid was found to be unsuitable owing to its insolubility in aqueous media. Electron microscopy indicated that human sperm do not undergo the acrosome reaction while penetrating cervical mucus in vitro.

Caffeic Acids↗

The effect of a single sauna exposure on spermatozoa.

Semen was collected at weekly intervals for 3 wk before and 10 wk after the sauna exposure at 85 degrees C for 20 minutes. The numbers, morphology, ultrastructure, motility, viability and metabolism of the sperm was assessed. Sperm numbers fell within one wk and slowly returned to normal in 5 wk. The earliest ultrastructural change was swelling of the plasma membrane, followed by an increase in the number of immature forms and disorganization of the arrangement of the mitochondria. Motility, glucose utilization and lactic acid accumulation of the sperm rose temporarily immediately after sauna.

Glucose↗

Unmyelinated nerve fibres in feline acrylamide neuropathy.

Electronmicroscope studies have been performed on the greater splanchnic nerve and the nerve to the medial head of gastrocnemius muscle of control and acrylamide poisoned cats. Degeneration of unmyelinated as well as of myelinated fibres was observed in both nerves. In cats severely poisoned with acrylamide, some very large unmyelinated axons undergoing early degeneration were seen in the splanchnic nerve. In the nerve to medial head of gastrocnemius, there was a decrease in the proportion of large diameter unmyelinated axons.

Acrylamides↗

Acrylamide autonomic neuropathy in the cat. Part 1. Neurophysiological and histological studies.

Neurophysiological and histological studies have been performed on the sympathetic nervous system of cats poisoned with acrylamide. The neurophysiological studies indicate that the large and small diameter myelinated fibres are damaged in the sympathetic nervous system in association with damage to the fibres of the peripheral nervous system. Quantative histological studies confirmed and extended the neurophysiological findings; there was a loss of myelinated fibres of all diameters from the sympathetic, parasympathetic and peripheral nervous system.

Acrylamides↗

Acrylamide autonomic neuropathy in the cat. Part 2. Effects on mesenteric vascular control.

Mesenteric blood flow has been studied in cats poisoned with acrylamide. In severely poisoned animals, there is impairment of the neural control of the mesenteric vascular bed. The diminished response of the mesenteric bed to tyramine administration, the increased response to phenylephrine and noradrenaline and the failure of the nerve endings to take up exogenous noradrenaline are indicative of damage to the postganglionic unmyelinated fibres. The studies support the view that disturbance of blood pressure control in autonomic neuropathy is related to the impaired vasomotor control of the splanchnic bed.

Acrylamides↗