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Biomedical subjects

C E Hunt

Publications and source records attributed to C E Hunt.

At least 19 recordsLinked to original sources

Comparison of 2-channel and 4-channel pneumograms.

To determine whether the addition of air flow and O2 saturation (SaO2) channels improves sensitivity of the pneumogram in identifying cardiorespiratory pattern abnormalities, 2- and 4-channel pneumograms (PG-2 and PG-4) were simultaneously recorded in 91 consecutive infants. Forty-one infants (45%) had cardiorespiratory symptoms, and 50 were asymptomatic. Pneumograms were considered abnormal for any of the following: apnea greater than or equal to 20 seconds, heart rate less than 80 bpm for greater than 5 seconds in preterm and less than 60 bpm in full-term infants (bradycardia), shorter apnea with bradycardia or desaturation, periodic breathing greater than 7% of total sleep time in preterm and greater than 4% in full-term infants, or SaO2 less than 85% for greater than 5 seconds. Both recordings were normal in 72% of infants and abnormal in 24%. In only 4% were the PG-4 abnormal when the PG-2 were normal, in all instances due to minimum SaO2 levels of 77-84% for 5-19 seconds associated with central apnea of intermediate duration (three infants) or with mixed apnea. The difference in frequency of abnormal results between the PG-2 and PG-4 recordings was not statistically significant (X2). In conclusion, although PG-4 do increase the scope of physiological information obtained in infants with cardiorespiratory events, this short-term study does not establish whether this increase results in any long-term benefits. Further, at least in this number and these types of at-risk infants, PG-4 do not improve the sensitivity of cardiorespiratory recordings for detecting abnormalities.

Bradycardia

Congenital central hypoventilation syndrome: diagnosis, management, and long-term outcome in thirty-two children.

The diagnosis, management, and long-term outcome of 32 patients with congenital central hypoventilation syndrome are summarized. Sleep hypoventilation was severe in all cases, resulting in an alveolar carbon dioxide pressure (mean +/- SEM) of 62 +/- 2.5 mm Hg and a hemoglobin saturation of 65% +/- 3.3% without ventilatory or arousal response. Awake hypoventilation on initial assessment was present in 12 of the 32 patients, resulting in an alveolar carbon dioxide pressure of 58 +/- 2.2 mm Hg and a hemoglobin saturation of 59% +/- 7%. Associated conditions included pulmonary hypertension or cor pulmonale or both (78%), heart block and sick sinus syndrome requiring a cardiac pacemaker (two patients), mild atrophy by cranial imaging evidence (40%), seizures (72%), normal brain-stem auditory evoked responses in all but one patient tested, ganglioneuroblastomas (one patient), Hirschsprung disease (16%), and ophthalmologic abnormalities (60%). Growth was deficient in 44% of patients; hypotonia or major motor delay or both were apparent in all. Twenty-two patients are living; 12 of them require continuous ventilatory support and 10 breathe spontaneously while awake and require ventilatory support while asleep. Ten patients have died. Autopsy performed in six cases indicated diffuse central nervous system astrocytosis, gliosis, and atrophy but no primary brain-stem abnormality. Although these data support a diffuse central nervous system process, the specific cause and the mode of inheritance remain unclear. With early diagnosis and careful ventilatory management, the sequelae of hypoxia and morbidity should be minimized and long-term outcome improved.

Child

Dietary polyunsaturated to saturated fatty acid ratio alters hepatic LDL transport in cynomolgus macaques fed low cholesterol diets.

To determine effect of interaction between dietary cholesterol and triglyceride, i.e., polyunsaturated to saturated (P:S) fatty acid ratio, on LDL metabolism, male cynomolgus macaques were fed purified diets for 83 wk with cholesterol levels of 0.01, 0.06 and 0.50 mg/kJ and P:S ratios of 0.5 and 0.9, oleic acid constant. There were six groups of five animals each (cholesterol, mg/kJ--P:S ratio): Group 1, 0.01--0.5; Group 2, 0.01--0.9; Group 3, 0.06--0.5; Group 4, 0.06--0.9; Group 5, 0.50-0.5; Group 6, 0.50-0.9. LDL (1.019 less than d less than 1.063 kg/L) and glucosylated LDL were iodinated for turnover studies. Hepatic LDL transport was determined using 125I-tyramine-cellobiose-LDL as tracer. Plasma cholesterol increased in proportion to dietary cholesterol, and concentrations (mmol/L) at 77-78 wk were (mean +/- SEM): Group 1, 434 +/- 0.31; Group 2, 3.03 +/- 0.14; Group 3, 8.28 +/- 1.48; Group 4, 7.34 +/- 1.31; Group 5, 15.54 +/- 1.44; Group 6, 15.54 +/- 1.41. LDL cholesterol was 45% higher in Group 1 (2.43 mmol/L) than in Group 2 (1.68 mmol/L). In vivo studies showed that LDL clearance was suppressed by excess dietary cholesterol; receptor-independent LDL clearance was relatively constant. Hepatic LDL protein transport was greater in Group 2 (P:S 0.9) compared with Group 1 (P:S 0.5). The LDL protein synthetic rate was lower in Groups 2, 4 and 6 (P:S 0.9) relative to Groups 1, 3 and 5 (P:S 0.5). We conclude that in this model hepatic LDL receptor activity is altered by degree of saturation in dietary triglycerides when dietary cholesterol is minimal, and that saturated dietary triglycerides enhance LDL protein secretion when dietary cholesterol is ample.

Animals

The cardiorespiratory control hypothesis for sudden infant death syndrome.

One or more abnormalities in cardiorespiratory control is the most compelling explanation for SIDS. Elucidation of the interrelationships between arousal responsiveness and gasping may be crucial to a better understanding of SIDS pathophysiology. The complex interactions need to be examined between arousal, autoresuscitation, and the other components of cardiorespiratory control. Prospective identification trials will be difficult since no cardiorespiratory control parameter yet identified has sufficient sensitivity and specificity, and trials assessing multiple parameters will be costly and cumbersome. Furthermore, prospective identification will be worthwhile only if an effective intervention has been established. To the extent that SIDS deaths still occur during documented monitoring, detailed analyses of the recorded cardiorespiratory events should finally provide us with objective data as to the terminal pathophysiologic events in SIDS victims and their relationship to aberrant cardiorespiratory control.

Arousal

Apo B metabolism in the cynomolgus monkey: evidence for post-transcriptional regulation.

Previous studies have shown that hepatic apo B mRNA levels do not increase in animals fed high cholesterol diets, even though plasma apo B concentrations increase markedly. As a result, it has been suggested that the diet-induced increase in plasma apo B levels was due solely to an inhibited clearance of those lipoproteins. The present study was undertaken to test that hypothesis. Hepatic apo B mRNA levels were measured in liver biopsies taken from five male cynomolgus monkeys before and twice after, they began to consume a high cholesterol diet. The diet had no effect on hepatic apo B mRNA levels, even though it caused a 7-fold increase in the plasma apo B levels. However, measurements of the apo B secretion rate in eight separate monkeys (four chow-fed and four cholesterol-fed) by isotope dilution showed that apo B secretion by the liver was increased 4-fold in the cholesterol-fed monkeys. These data, taken together, indicate that apo B secretion is not regulated by the rate at which the apo B gene is transcribed, but at some point further along in the secretion pathway.

Amino Acid Sequence

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

The effect of independent variations in inspiratory-expiratory ratio and end expiratory pressure during mechanical ventilation in hyaline membrane disease: the significance of mean airway pressure.

The specific aspects of the respiratory cycle during mechanical ventilation that allow for optimum gas exchange are still controversial. To further clarify the relationship of inspiratory:expiratory ratio and positive end expiratory pressure to optimum ventilation and oxygenation, five premature lambs with severe hyaline membrane disease were ventilated with volume-present infant ventilators at I:E ratios of 1:4 and 1:1 and PEEP levels of 0, 5, and 10 cm H2O. For each I:E ratio/PEEP combination, pH, Pao2, PaCO2, PAO2, PACO2, peak inspiratory pressure, mean inspiratory pressure, and mean airway pressure were measured and compared. Optimum ventilation and oxygenation were related to MAP, but not to I:E ratio, PIP, or MIP. As MAP increased from 6 to 14 cm H2O, progressive improvement in Pao2, PaCO2 (A-a) DO2 and (a-A) DCO2 was evident. Above 14 cm H2O, there was progressive deterioration in these measurements. There was also a direct relationship between MAP and mean pleural pressure. These results indicate that during mechanical ventilation there is an optimum MAP at which gas exchange is best. Since MAP changes with any change in PIP, PEEP, or I:E ratio, it provides a useful composite measure of all pressures transmitted to the airways by the ventilator.

Airway Resistance