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Biomedical subjects

C E Hunt

Publications and source records attributed to C E Hunt.

At least 109 records · Page 6Linked to original sources

Serial serum zinc levels in preterm infants during parenteral and enteral feedings.

Weekly serum zinc levels during the neonatal period have been obtained in 17 preterm infants randomly assigned to a prospective feeding study. Nine neonates received a standard regimen of naso-jejunal feedings (group I) and eight matched infants received total parenteral nutrition (group II) for the first 2 wk, followed by enteral intake for the last 2 wk of the study period. No patient received supplemental zinc intake. Base-line serum zinc levels obtained before beginning feedings at 2 days of age were in the normal range and not significantly different, 121 +/- 15 and 135 +/- 8 micrograms/dl in groups I and II, respectively (mean +/- SEM). Serial serum zinc levels decreased progressively in both groups during the 4-wk study period, reaching a low of 80 +/- 7 micrograms/dl in group I and 85 +/- 10 micrograms/dl in group II. The progressive decline in serum zinc levels is postulated to be indicative of tissue depletion of zinc. Our data suggest that preterm infants fed either by short-term total parenteral nutrition or by transpyloric enteral feedings are at risk for marginal zinc deficiency states.

Enteral Nutrition↗

Diminished hypoxic ventilatory responses in near-miss sudden infant death syndrome.

The ventilatory response to hypoxia and to hypercarbia was assessed in 36 near-miss sudden infant death syndrome (N.M SIDS) and 23 control infants. Base-line measurements during non-REM sleep documented no significant difference in respiratory frequency, alveolar CO2 and O2 partial pressure (PAco2 and PAo2) or tidal volume between the N-M SIDS and control infants. In the N.M SIDS group, mean inspiratory flow and minute ventilation (VI) were significantly lower than in the control group (p less than 0.001 and p less than 0.01, respectively), and the slope of the ventilatory response to hypercarbia ((delta VI/Torr Paco2) was only 21 +/- 1.9 (SE) ml.kg-1 min-1 Torr PAco2 compared with 62 +/- 3.5 in controls (p less than 0.001). For both groups, the increase in ventilation with hypoxia appeared linear within the PAo2 range assessed (65-115 Torr) and was therefore expressed as the slope of the delta VI/PAo2 plot (ml.kg-1 min-1 per Torr PAo2). The slope of the hypoxic ventilatory response was significantly less in the N-M SIDS than in the control group, -8.3 +/- 1.0 VS. -19.9 +/- 1.5, respectively (p less than 0.001). In summary, in comparison to control infants, N-M SIDS infants as a group have a significantly smaller increase in VI in response to hypoxia as well as to hypercarbia.

Arousal↗

Abnormal hypercarbic and hypoxic sleep arousal responses in Near-Miss SIDS infants.

Arousal responses (AR) to hypercarbia and to hypoxia were ascertained in 25 N-M SIDS infants and 21 control infants in whom ventilatory responses to hypercarbia and hypoxia were also measured. Although the frequency of a positive AR to hypercarbia was not significantly less in the N-M SIDS compared to control group, the overall pattern was a generally absent AR in the lowest hypercarbic ventilatory response slope group progressing to a generally positive AR in the highest hypercarbic response slope group. Among the 25 infants having a positive hypercarbic AR, the Mean (+/- SEM) PACO2 at which arousal occurred was 48.5 +/- 1.6 in N-M SIDS versus 42 +/- 1.2 mmHg in control infants (p less than .001). The overall pattern for hypoxic AR was also a generally absent AR in the lowest hypoxic ventilatory response slope group progressing to a generally positive AR in the highest response slope group. Although the PAO2 level at which an AR occurred did not differ in the two groups, a positive hypoxic AR occurred in 76% of the control versus only 29% of the N-M SIDS group (p less than .01). In summary, infants with a clinical N-M SIDS history and diminished ventilatory response slopes have as a group a concomitant abnormality in hypercarbic and/or hypoxic arousal.

Arousal↗

Indomethacin treatment for symptomatic patent ductus arteriosus: a double-blind control study.

A double-blind control study was designed to determine the efficacy and safety of indomethacin treatment of patients with symptomatic patent ductus arteriosus. Infants with severe respiratory distress syndrome and symptomatic patent ductus arteriosus were eligible for the prospective study if the ratio of left atrial/aortic root diameter remained greater than or equal to 1.3:1 following a 24-hour period of medical management. Thirty-nine eligible infants were randomly assigned to the control or indomethacin group and given 0.2 mg/kg of enteral indomethacin or placebo in a double-blind manner. Second and third doses were administered at 24-hour intervals in phase 1 (17 patients), and at eight-hour intervals in phase 2 (22 patients). The 75% patent ductus arteriosus closure rate with indomethacin treatment in phase 1 was not statistically significant due to a 44% spontaneous closure rate in the control group. In phase 2, however, 85% of the indomethacin group demonstrated patent ductus arteriosus closure vs only 11% in the matched control group (P less than .01). Although no indomethacin side effects occurred in phase 1, in phase 2 indomethacin administration was associated with minimal, but statistically significant, transient impaired renal function and, in three infants (23%), mild upper gastrointestinal bleeding. In summary, enteral administration of three 0.2 mg/kg indomethacin doses at eight-hour intervals thus appears to be a safe and effective alternative to surgical closure.

Clinical Trials as Topic↗

Prospective controlled study of parenteral nutrition-associated cholestatic jaundice: effect of protein intake.

The development of transient cholestatic jaundice is a well-recognized complication of prolonged parenteral nutrition. The etiology and long-term significance have not been established. This report describes a prospective controlled study designed to compare the hepatic effects of two different parenteral protein intakes, a lower protein regimen of 2.3 gm/kg/day and a higher protein regimen of 3.6 gm/kg/day. The minimum criterion for ChJ was a direct bilrubin greater than or equal to 2.0 mg/dl. Eighty-two consecutive infants completed the study. No ChJ occurred in the 39 infants who received PN for less than two weeks. In 43 infants requiring PN for at least two weeks, the incidence of ChJ was similar in the two groups, six infants in the LP and seven in the HP group. However, infants prospectively assigned to the HP group developed ChJ earlier than the LP group, 27 +/- 6 days (P less than 0.01), and achieved a significantly greater peak direct bilrubin level, 8.4 +/- 1.6 versus 3.2 +/- 0.3 mg/dl (P less than 0.001). Retrospective comparison of the 13 ChJ infants to the 30 long-term PN infants without ChJ revealed a significantly greater daily dextrose intake in those developing ChJ, 16.2 +/- 1.1 gm/kg/day versus 13.4 +/- 0.9 in the group without ChJ (P = 0.025). Our results indicate that an increased parenteral protein intake is associated with an earlier and increased magnitude of ChJ and suggest than an increased dextrose intake may be associated with an increased frequency of ChJ.

Bile↗

Reversible central apnea in an infant with cyanotic heart disease.

The purpose of this report is to present the findings in a neonate with tetralogy of Fallot and a history of prolonged sleep-related apnea requiring resuscitation. At a baseline arterial oxygen pressure of 46 mm Hg, his preoperative responses to carbon dioxide during non-REM sleep (26.1 and 26.6 ml/kg/min/mm Hg of alveolar carbon dioxide tension [PACO2]) were identical to those reported in near-miss sudden infant death syndrome. Following a systemic-pulmonary arterial shunt, the arterial saturation reached 95 percent, and no further apnea occurred. The prompt normalization of the response to carbon dioxide following surgery (75.2 and 75.4 ml/kg/min/mm Hg of PACO2) indicates that, unlike infants with the sudden infant death syndrome, a low sensitivity to carbon dioxide in infants with cyanotic heart disease may be dependent on hypoxemia and, thus, reversible.

Carbon Dioxide↗

Characterization of an auto-rosette inhibitory fraction in mouse serum.

Normal mouse sera inhibited auto-erythrocyte rosette formation by mouse thymus cells. Serum inhibitory factor was associated with high density lipoprotein (HDL) isolated from mouse sera with sequential flotation ultra-centrifugation techniques. Other portions of normal mouse sera, i.e., very low density lipoprotein (VLDL), low density lipoprotein (LDL), lipoprotein-free serum, and delipidated HDL had little or no inhibitory activity. A 20-fold purification with 68% recovery of total serum activity was obtained by this isolation procedure. HDL from the serum of BALB/c, C57BL/6, C3H, and NZB/BIN mice inhibited BALB/c auto-rosettes. Inhibition was observed when lymphocytes were preincubated with HDL and then washed before assaying, but there was no inhibition when erythrocytes were pretreated.

Animals↗

The effect of overdistention of the lung on pulmonary function in beagle puppies.

The removal of one lung from a beagle puppy results in minimal interference with lung function or the arterial gases. The removal of air from the empty pleural cavity results in a shift of the mediastinum and overdistention of the contralateral lung. An immediate decrease in the PO2 and increase in the PCO2 is seen. Significant increase in the alveolar-arterial CO2 gradient reflected marked increase in dead space ventilation. Biopsies of the overdistended lung demonstrated emphysema and disruption of alveoli. These changes may explain some of the deterioration of lung function and the complication of contralateral pneumothorax following repair of a Bochdalek diaphragmatic hernia. Our study suggests that the mediastinum should be stabilized in the midline after repair of a diaphragmatic hernia or after a pneumonectomy in an infant or small child.

Animals↗

Respiratory and nonrespiratory effects of doxapram in congenital central hypoventilation syndrome.

Doxapram is a respiratory stimulating drug that affects both peripheral chemoreceptors and medullary respiratory and nonrespiratory neurons. We administered doxapram 60 2 infants with congenital central hypoventilation syndrome. In 6 separate trials at a dose range of 0.32 to 2.0 mg per kg of body weight per min, quiet-sleep tidal volume increased from 4.9 +/- 1.0 to 8.5 +/- 0.9 ml per kg of body weight, minute ventilation increased from 140 +/- 38 to 286 +/- 31 ml per kg of body weight per min, and alveolar PCO2 decreased from 60 +/- 5 to 32 +/- 2 mm Hg. In all instances, the maximal quiet-sleep ventilatory response was achieved within 10 min. The ventilatory response to steady-state CO2 breathing was not improved with doxapram. A continuous infusion of doxapram for 5.2 days in one infant successfully maintained normal quiet-sleep ventilation. In both infants, multiple nonrespiratory effects of doxapram occurred; enteral administration was associated only with generalized neuromuscular stimulation, but the 5-day intravenous infusion was also associated with acute hepatotoxicity and a perforated duodenal ulcer. The medullary respiratory neurons in central hypoventilation syndrome may be incapable of responding to doxapram, and the ventilatory responses observed may be due entirely to stimulation of peripheral chemoreceptors. Although quiet-sleep ventilation can be successfully maintained with intravenous and enteral administration of doxapram, and tachyphylaxis has not been observed, we have been unable to avoid at least the neuromuscular manifestations of nonrespiratory medullary stimulation.

Chemical and Drug Induced Liver Injury↗

The effects of changes of maternal PaO2 and PaCO2 on the fetal PaO2 and PaCO2--in vivo study.

Umbilical PaO2 and PaCO2 were continuously monitored in vivo in acute fetal lamb preparations with a semipermeable membrane connected to a mass spectrometer. The response time of this system (0 to 90% of final value) was 36 sec. In seven pregnant sheep (128--135 days gestation) the maternal inspired mixture was abruptly changed and the following changes in fetal PaO2 and PaCO2 were observed: (1) 100% O2 to room air: PaO2 decreased from 21.5 +/- 0.8 (mean +/- SEM) to 14 +/- 1.1 mm Hg at a rate of 1.63 +/- 0.33 mm Hg/min. Following return to 100% O2 the PaO2 returned to 21 +/- 1.1 mm Hg at a rate of 2.44 +/- 0.4 mm Hg/min. (2) 100% O2 to 12% O2/10% CO2: after 6 min the PaO2 fell from 19.3 +/- 1.3 to 6.3 +/- 0.3 mm Hg at a rate of 4.65 mm Hg/min and the PaCO2 rose from 37 +/- 8 to 70 +/-5 mm Hg. At 100% O2 the PaO2 returned to 19 +/- 1.0 mm Hg at a rate of 11.76 +/- 0.086 mm Hg, the PaCO2 to 39 +/- 7 mm Hg. (3) 100% O2 to 90% O2/10% CO2. The PaO2 and PaCO2 increased by 4.7 and 22 mm Hg, respectively. The changes of fetal PaO2 and PaCO2 occurred after 1 minute of changing in maternal inspired mixture except in the transition from 12% O2/10% CO2 to 100% O2 (34 +/- 12 sec). Following the reinstitution of 100% the fetal PaO2 and PaCO2 returned to their previous values within 4 and 16 min, respectively.

Animals↗

Essential fatty acid deficiency in neonates: inability to reverse deficiency by topical applications of EFA-rich oil.

Correction of essential fatty acid deficiency by transcutaneous absorption of topically applied EFA-rich oil has been reported. We measured serum EFA levels in two groups of neonates receiving fat-free total parenteral nutrition: nine control patients after 16 and 25 days of TPN, and six patients before and 12 days after beginning cutaneous application of 100 mg/kg/day of linoleic acid as sunflower seed oil. Progressive biochemical EFA deficiency occurred in all but one of the control patients. Of the six patients receiving 100 mg/kg/day of linoleic acid, one patient with mild deficiency improved, but progressive EFA deficiency occurred in the other five patients. Serum EFA levels were also measured in four patients following 76 days of TPN and daily application of high doses of topical safflower oil, all of whom had severe biochemical EFA deficiency. The topical application of EFA-rich oil cannot be assumed to be uniformly effective in reversing or preventing EFA deficiency. The transcutaneous absorption of essential fatty acids must be documented by appropriate measurements of EFA in serum lipids.

Administration, Topical↗

Vitamin A deficiency and new bone growth: histologic changes.

Using a standardized guinea pig model system, the histologic appearance of newly formed bone from vitamin A deficient, vitamin A adequate and retinoic acid treated animals was compared. Microscopic examination of the histologic sections of bone collected from vitamin A deficient guinea pigs indicated the presence of highly cellular and loosely woven bone spicules. This model system is an osteoblastic model, since osteoclasts are essentially absent in tissue formed in 14-day implants. Thus, new bone formation in the vitamin A deficient guinea pig reveals morphologic changes which are principally mediated through the osteoblastic process.

Animals↗

Central hypoventilation syndrome: experience with bilateral phrenic nerve pacing in 3 neonates.

Successful long-term phrenic nerve pacing has been reported in adults with acquired central hypoventilation syndrome. This report summarizes our experience with phrenic nerve pacing in 3 infants with congenital central hypoventilation syndrome. The electrodes were implanted in the lower thoracic portion of each phrenic nerve. In all patients. bilateral simultaneous pacing was required to maintain an adequate arterial PO2, tidal volume, and minute ventilation during quiet sleep. Case 1 died of problems primarily related to the severe cor pulmonale that had been present before pacemaker insertion; at autopsy, the pacemaker system was intact and there were no significant phrenic nerve abnormalities. Case 2 later developed failure of awake ventilatory control and died because of extensive phrenic nerve damage incurred by 19 days of continuous pacing. Case 3 has received quiet sleep pacemaker support since September 1977 and has been able to maintain normal quiet sleep ventilation in this manner. Phrenic nerve pacing can be successful in infants as long as continuous pacing is not required. Bilateral simultaneous pacing appears to be an appropriate alternative to home-based intermittent positive-pressure breathing for long-term management of children with central hypoventilation syndrome.

Electric Stimulation↗

Congenital central hypoventilation syndrome: a pathologic study of the neuromuscular system.

An infant with congenital central hypoventilation was managed by bilateral phrenic nerve pacing for 3 months. He died at 8 months of age, following 19 days of continuous bilateral pacing necessitated by the eventual loss of voluntary as well as autonomic ventilatory control. The phrenic nerves showed axonal dystrophy at the site of electrode implantation and more severe distal degeneration. Focal neurogenic atrophy was seen in the diaphragmatic muscle. These changes were attributed to electrical injury resulting from the period of continuous pacing. The most significant neuropathologic finding was a mild generalized decrease in the density of neurons and myelinated nerve fibers in the respiratory centers of the medulla. These morphologic abnormalities were attributed to a sublethal intrauterine lesion that would be the first example of a morphologic correlation with the functional abnormality in congenital central hypoventilation.

Brain↗

Description of obesity in the PBB/Ld mouse.

A new strain of obese mouse, the PBB/Ld, has been studied in terms of fat pad cellularity, serum insulin and blood glucose levels, and response to gold thioglucose injections. Age-matched C57B1/6J mice were used as controls. Adipocyte size and number in the major fat depots were determined at various ages from weanling to maturity in the PBB/Ld and C57B1/6J strains. Results indicated that obesity in the PBB/Ld was due to hypertrophy of adipocytes in retroperitoneal and subcutaneous fat depots and to hypertrophy and hyperplasia in the epididymal fat pad. PBB/Ld mice also developed hyperinsulinemia and hyperglycemia and these findings have been discussed in terms of the developmental changes in fat pad cellularity. The injection of gold thioglucose led to increased food intake in both PBB/Ld and C57B1/6J mice. Hyperphagia was also present in the PBB/LD control group, but increased efficiency of converting calories to body weight was not observed in this group when compared to control C57B1/6J mice. The characteristics of obesity seen in the PBB/Ld mouse are discussed and comparisons are made to similar studies in other rodent models of obesity.

Animals↗