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Biomedical subjects

M E Morgan

Publications and source records attributed to M E Morgan.

At least 37 records · Page 2Linked to original sources
PubMed1992

Postnatal encephaloclastic porencephaly--a new lesion?

A previously unrecognised and distinctive pattern of severe brain injury in extreme preterm neonates was observed recently. Fifteen neonates of birth weight 600-1270 g and gestation of 24-32 weeks showed relatively late development on cerebral ultrasound scan of extensive dense and cystic lesions involving the periphery of the brain. The extent of the changes was confirmed at postmortem examination in 11 babies. These changes have been called encephaloclastic porencephaly. The population of babies in whom this has occurred and their clinical outcome has been reviewed, with comparison between the evolution of the ultrasound changes and pathological findings at postmortem examination.

Brain↗
PubMed1992

Caffeine or theophylline for neonatal apnoea?

Caffeine, in the dose usually recommended (12.5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controlled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. All three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours. The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response.

Apnea↗
PubMed1990

I-131 accumulation in gastric pull-up simulating pulmonary metastases on total-body scan for thyroid cancer.

A follow-up total-body I-131 scan in a patient with follicular thyroid carcinoma demonstrated radionuclide accumulation in the right hemithorax. Originally thought to be pulmonary metastatic thyroid carcinoma, the uptake region proved to be intrathoracic gastric mucosa. The patient had been treated for squamous cell esophageal carcinoma by esophagogastrostomy reconstruction with gastric pull-up. This unusual imaging pattern could have been interpreted as metastatic disease in the absence of complete patient records, an appreciation of normal gastric concentration patterns of I-131, and corroborative imaging study analysis.

Carcinoma, Squamous Cell↗
PubMed1990

Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin.

The effects on gut blood flow velocities of parenteral indomethacin (0.2 mg/kg) given either quickly as a bolus or slowly as an infusion were compared in consecutive studies of two groups of infants with symptomatic patent ductus arteriosus. In the presence of patent ductus arteriosus the range of velocities in the superior mesenteric artery before indomethacin was given was characterised by pronounced abnormalities including absent--or in some cases even retrograde--diastolic flow. In eight subjects the first rapidly given bolus dose of indomethacin (duration 20 seconds or less) caused a pronounced and sustained fall in the velocity of the superior mesenteric artery blood flow (mean peak systolic velocity (cm/second): before 74; after 38; median time to maximum fall 7.4 minutes; median time to recovery 50 minutes). A further 10 subjects received their first dose of indomethacin by slow infusion (duration 30-35 min) and the percentage fall in peak systolic velocity was both substantially less (22% compared with 47%) and later (median time to maximum fall 37.3 minutes) than after rapid infusion. Qualitatively similar but smaller changes were seen in the coeliac axis. Return of antegrade end diastolic flow in the superior mesenteric artery within one hour of the first dose of indomethacin was a good predictor of subsequent closure of the ductus. These data suggest that there is a profound disturbance in mid gut perfusion in infants with patent ductus, which is exacerbated by indomethacin given rapidly by intravenous bolus. They may also provide a rational explanation for the well recognised association between necrotising enterocolitis and both patent ductus arteriosus and indomethacin administration. The unwanted effects of the indomethacin are abrogated by slow infusion, without loss of efficacy in closure of the ductus.

Blood Flow Velocity↗
PubMed1989

Methylxanthine effects on caudate dopamine release as measured by in vivo electrochemistry.

The effects of caffeine (1,3,7-trimethylxanthine) and theophylline (1,3-dimethylxanthine) on caudate dopamine release were examined in urethane anesthetized and freely moving rats using in vivo electrochemistry. In anesthetized animals, all doses (150, 250, and 500 mumole/kg, i.p.) produced significant decreases in caudate dopamine (DA) release, which were 14%, 30% and 58%, respectively, at 30 min. The decrease in caudate DA release appeared to be a selective effect with respect to drug and brain region. D-amphetamine (37 mumole/kg, i.p.) increased the caudate signal over a 150 min period. Caffeine, 250 mumole/kg, increased norepinephrine (NE) release in hippocampus by 37% at 30 min and 58% at 150 min. Motor cortical NE release was increased by 8% at 30 min and 44% at 150 min. In freely moving rats, caffeine and theophylline, 75 mumole/kg, increased caudate DA release by 39% and 66%, respectively, at 60 min. Caffeine, 250 and 500 mumole/kg, decreased caudate DA release by 31% and 52%, respectively, at 30 min. Theophylline, 250 mumole/kg, increased release by 25% at 75 min. A 500 mumole/kg dose of theophylline decreased caudate DA release by 44% at 30 min. Measurement of caudate methylxanthine concentrations showed that caudate caffeine levels were significantly higher than those of theophylline. These data are the first to show in an intact animal that methylxanthines affect the regional release of catecholamines (CA) in the central nervous system. This effect is dose dependent.

Anesthesia↗
PubMed1989

Does mechanical ventilation precipitate gastro-oesophageal reflux during enteral feeding?

The influence of intermittent positive pressure ventilation on gastro-oesophageal reflux in preterm infants is not known. In many neonatal units, however, concern that ventilation may increase gastro-oesophageal reflux (and therefore aspiration) leads to avoidance of enteral feeding during ventilation. We have therefore performed a crossover study of gastrooesophageal reflux by monitoring lower oesophageal pH in a group of nine enterally fed, very low birthweight infants both during assisted ventilation and normal breathing. All infants had less reflux during intermittent positive pressure ventilation (mean (SEM) reflux index 2.3 (0.6%)) than during normal breathing (mean (SEM) reflux index 6.1 (1.1%)). Assisted ventilation was associated with a significant reduction in the gastro-oesophageal pressure gradient, an effect which may be related to the use of positive and end expiratory pressure during ventilation. These data show that fear of gastro-oesophageal reflux should not preclude the use of enteral feeding in preterm infants receiving ventilation.

Enteral Nutrition↗
PubMed1989

Gastro-oesophageal reflux in preterm infants.

Gastro-oesophageal reflux in very low birthweight infants was studied using a new 1 mm monocrystalline antimony oesophageal pH electrode. Gastro-oesophageal reflux was detected in 30 (85%) subjects. The mean (SEM) number of episodes of reflux in 24 hours was 12.1 (2.1), and 3.2 (0.6) lasted over five minutes. The mean reflux index was 4.5 (1.0)%, and the longest episode 17.1 (4.6) 17.1. Reflux was unrelated to postconceptional age or to resting lower oesophageal sphincter pressure. The mean reflux index was low at rest before feeds, being 1.8 (0.6)%, and increased slightly after feeds (3.8 (1.0)%), but was significantly increased after nursing care to 16.4 (3.0)%, and while xanthines were being given (5.9 (1.6)%. A subgroup of seven infants with xanthine resistant apnoea had severe gastro-oesophageal reflux that was not clinically apparent (reflux index 27.4 (3.6)%). Successful treatment of the reflux (reflux index: 3.6 (1.2)%) was associated with cessation of the apnoea. We conclude that gastro-oesophageal reflux is common, and is usually not clinically apparent, even when severe. It is important to consider gastro-oesophageal reflux in the differential diagnosis of xanthine resistant apnoea in preterm infants.

Apnea↗
PubMed1988

Polymorphonuclear leukocyte inhibition by therapeutic concentrations of theophylline is mediated by cyclic-3',5'-adenosine monophosphate.

Although theophylline has been used for many years as a principal agent in treatment of reversible obstructive airway disease, the mechanism of drug activity at therapeutic concentrations remains unclear. Because inflammatory mediators generated by polymorphonuclear leukocytes (PMN) may be important in the pathogenesis of airway hyperreactivity, the effects of theophylline upon PMN activation were studied. Theophylline (9 micrograms/ml, 50 microM) inhibited PMN leukotriene B4 generation by 50%, oxygen metabolite generation by 60%, and decreased the concentration of isoproterenol required to cause 50% maximal inhibition (EC50) from 13 to 3.3 nM. The same theophylline concentration increased PMN cAMP by 196% at 45 s after cell activation. A higher theophylline concentrations (18 micrograms/ml, 100 microM) decreased leukotriene B4 generation by more than 90%. Eight healthy volunteers were studied before and after 1 wk of oral theophylline administration (mean plasma theophylline level achieved was 9.4 micrograms/ml). Basal and 1-min postactivation cAMP concentrations were increased 160 and 157%, respectively, in PMN specimens after theophylline administration. The EC50 for isoproterenol was reduced by 50%, and the cAMP elevation induced by isoproterenol was increased by 200%. Because theophylline inhibition of PMN function appeared to be associated with both an increase in cAMP and a decrease in intracellular calcium, these effects may be relevant to both the therapeutic and adverse pharmacologic actions of theophylline. Because inflammatory mediator release was reduced by low drug concentrations, inhibition of PMN function may be an effect of therapeutic theophylline administration.

Adult↗
PubMed1987

Additive effect of theophylline on the cardiac response to isoproterenol.

To ascertain the effect of theophylline on the cardiac chronotropic response to beta-adrenergic stimulation, isoproterenol dose-response curves in healthy young subjects were compared during saline and theophylline maintenance infusions. Each study was repeated 1 to 3 weeks later to evaluate reproducibility. Neither the dose of isoproterenol required to raise the heart rate by 25 bpm (2.32 +/- 0.81 vs. 1.55 +/- 0.46 micrograms on day 1 and 1.28 +/- 0.22 vs. 1.27 +/- 0.25 micrograms on day 2) nor the slopes of the dose-response curves were affected by theophylline. Higher heart rates were observed after isoproterenol bolus dosing during theophylline than during saline infusion because of additive chronotropic effects of theophylline and isoproterenol. Since theophylline does not interact in a synergistic fashion with isoproterenol, phosphodiesterase inhibition appears to be an unlikely mechanism of the chronotropic effect of methylxanthines at therapeutic concentrations.

Adult↗
PubMed1987

The rCBF response to Diamox in normal subjects and cerebrovascular disease patients.

Age-related norms for the regional cerebral blood flow (rCBF) response to Diamox (acetazolamide) were based on studies of 55 normal subjects at rest and on studies of 33 of these 55 normal subjects following an intravenous injection of Diamox (22 mg/kg). After the Diamox injection, rCBF increased at all locations measured in all subjects. On average, rCBF increased 1.7 times. The following were found for rCBF in both resting and Diamox-treated subjects: 1) rCBF decreased significantly with increasing age; 2) slope and intercept for the regression of rCBF on age were largest for frontal detectors, intermediate for parietal detectors, and smallest for occipital detectors; 3) rCBF hyperfrontality was most noticeable in younger subjects; 4) in subjects of any age, 95% confidence intervals for rCBF were relatively large (expected value +/- 30%) and lower 95% confidence intervals for Diamox rCBF tended to overlap the upper 95% confidence intervals for resting rCBF; and 5) side-to-side percentage difference in rCBF did not have a significant regression on age and tended to be less than 10% to 20%. Diamox did not have an important effect on blood pressure, pulse rate, or respiratory rate. The normative data for the rCBF response to Diamox was used in evaluating 20 patients with cerebrovascular disease. Forty percent of these patients, all of whom exhibited angiographic evidence of potentially hemodynamically significant lesions, had normal rCBF at rest and after Diamox injection. Twenty percent had normal resting flows with abnormal Diamox-activated flows. Asymmetry in rCBF was the most sensitive indicator of a potential abnormality in cerebral perfusion. Thirty percent of the abnormal studies showed only significant asymmetry. It is suggested that rCBF studies at rest and after Diamox treatment, with age-related norms, may be useful in the management of patients with cerebrovascular disease.

Acetazolamide↗
PubMed1985

Posthaemorrhagic hydrocephalus in newborn term infants.

Intraventricular haemorrhage may occur de novo in previously well, term newborn infants. In a group of six neonates a high incidence of posthaemorrhagic hydrocephalus was found. Posthaemorrhagic hydrocephalus may be more common in full term newborn infants than previously recognised.

Cerebral Hemorrhage↗
PubMed1985

Behavioral effects following rehabilitation from postnatal exposure to lead acetate.

At 21 days of age three groups of male hooded rats of the Sprague-Dawley strain were exposed to either untreated water or lead acetate at concentrations of 25 or 50 ppm provided ad lib. in the drinking water for 40 days. When tested for spontaneous alternation, the subjects receiving both 50 ppm and 25 ppm lead acetate exhibited significantly reduced rates of alternation below those of untreated control subjects. Immediately subsequent to testing, lead was removed from the diet of the experimental groups and water substituted which was provided ad lib. for the duration of the experiment. This regimen of rehabilitation was continued for 70 days at which time all subjects were tested on the problems of the Hebb-Williams closed-field maze-learning task. No significant differences were found in the time taken to traverse the maze enclosure, the number of squares traversed, or in the total number of error zones entered over the 12 test problems, although significantly increased latencies to leave the start box were noted for subjects previously exposed to lead acetate. These data indicate that some deficits produced by postweaning lead acetate exposure may be reversible and not persist beyond a period of rehabilitation.

Animals↗