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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

Cardiorespiratory monitoring.

Documented monitoring has many actual or potential advantages compared to undocumented monitoring. Due to the occurrence of monitor alarms in virtually all monitored infants and the potential for undue parental concern or noncompliance when excessive false alarms do occur, documented monitoring needs to become the standard for home electronic surveillance. The increased cost should be more than offset by net reductions in total duration of home monitoring and will be minimized by the integration of the home monitor and event recording components. Documented monitoring will quantify the frequency, duration, and type of each true event, whether related to apnea, bradycardia, desaturation, or a combination thereof. The availability of routine documented monitoring including SaO2 will be of dramatic benefit in enhancing our understanding regarding the pathophysiology of apparent life-threatening events and sudden death, providing the clinician with a heretofore unavailable powerful diagnostic and therapeutic modality.

Blood Gas Monitoring, Transcutaneous

Breathing control disorders in infants and children.

Pediatric breathing control disorders can be disastrous if not promptly recognized and treated. Diagnostic techniques and management options are discussed in the context of essential clinical features of five major entities: neonatal apnea, obstructive sleep apnea, central hypoventilation syndrome, "apparent life-threatening events," and sudden infant death syndrome.

Apnea

Effects of continuous low-frequency pacing on immature canine diaphragm.

Although diaphragm pacing has been shown to be a practical method of supporting ventilation in children, its usefulness has been limited because of concern that continuous (24 h/day) diaphragm pacing would fatigue and damage the diaphragm. We examined the functional and structural effects of continuous low-frequency diaphragm pacing on the left hemidiaphragm of five immature dogs aged 65 +/- 2 (SD) days at onset of pacing. Stimulus parameters approximated those required to pace infants: frequency 11.1 Hz, inspiratory time 810 ms, and respiratory rate 20 breaths/min. Animals were paced 24 h/day for 24-28 days. Paced tidal volumes and airway occlusion pressures were unchanged at low (less than 15 Hz) stimulus frequencies but were reduced at high (greater than 20 Hz) stimulus frequencies. Although histologically the paced hemidiaphragms appeared normal, histochemical studies showed a conversion from a mixture of type I (54%) and type II (46%) fibers to a uniform population of type I fibers with high oxidative enzyme activity. Transformation of muscle type was also demonstrated by pyrophosphate gel electrophoresis; fast and slow isomyosin bands were noted in control specimens, whereas only slow isomyosin was identified in paced specimens. Thus, in immature dogs, continuous low-frequency pacing affects both function and structure of the diaphragm.

Action Potentials

Prenatal cocaine exposure is associated with respiratory pattern abnormalities.

As retrospectively determined, the rate of sudden infant death syndrome in 66 infants prenatally exposed to cocaine was 15%, compared with only 4% among infants exposed to opiates. This prospective evaluation of cardiorespiratory pattern in 32 cocaine-exposed and 18 methadone-exposed infants was therefore performed to further evaluate the effects of intrauterine exposure. The two groups were similar in maternal age, race, and cigarette, alcohol, and marijuana use and in gestational age, sex, and birth weight. Apnea density and episodes of periodic breathing exceeded the 95th percentile for normal infants in 12 (38%) of 32 of cocaine-exposed infants vs only 1 (6%) of 18 opiate-exposed infants. Five cocaine-exposed but no opiate-exposed infants had apnea of infancy, and all 5 of these infants had an abnormal cardiorespiratory pattern. In all 13 infants with an abnormal cardiorespiratory pattern, theophylline treatment resulted in normalization of the respiratory pattern and was associated with absence of any (further) clinical events. In summary, infants prenatally exposed to cocaine have a higher incidence of cardiorespiratory pattern abnormalities than do infants with methadone or no prenatal drug exposure.

Apnea

Loss of oxygen tolerance in newborn rabbits: relationship to changes in eicosanoid and antioxidant levels.

Relative tolerance of newborn animals to hyperoxia has been reported. This study investigated the age limitation of oxygen tolerance and mechanisms for its loss. Developmental changes in lungs of normoxic New Zealand rabbits were studied on days 1, 3, 4, 5, and 10 of life. These were contrasted with newborn and 7-day-old rabbits exposed to greater than 95% O2 for 65 hours. Normoxic rabbits demonstrated a decrement in bronchoalveolar lavage (BAL) 6keto-PGF1a, thromboxane B2, and lower lung catalase, total glutathione, and superoxide dismutase with maturation. Newborns were more tolerant to oxygen than 7-day-old rabbits. Oxygen exposure beginning on day 1 did not result in identifiable lung damage. Exposure beginning on day 7 resulted in microscopic evidence of injury and significant increases in BAL white cells, neutrophils and protein, and a trend toward higher BAL LTB4 compared to normoxic age-matched controls. Antioxidants were higher in the hyperoxic 7 day-olds, but remained lower than values in hyperoxic newborns. These results suggest that loss of oxygen tolerance in maturing rabbits is related to a developmental decrement in antioxidants and prostacyclin.

Animals

Role of eicosanoids in relative oxygen tolerance of newborn rabbits.

Prolonged exposure to hyperoxia can result in significant lung injury, although newborn animals are more oxygen-tolerant than adults. Mechanisms affording tolerance to the newborn are incompletely understood. This study examined the hypothesis that eicosanoids play a significant role in newborn oxygen tolerance. One litter of term newborn albino rabbits and 15 adult rabbits were exposed to 65 hours of greater than 95% O2. An additional litter of newborns served as a normoxic control. Normoxic newborn rabbits had very high quantities of 6-keto-PGF1a and low TXB2 in bronchoalveolar lavage (BAL) fluid. Sixty-five hours of oxygen exposure in newborn rabbits produced no evidence of lung injury on light microscopy, 97% of BAL white cells were alveolar macrophages and BAL protein was low. An equal period of oxygen exposure produced significant lung injury in adult rabbits. BAL fluid from oxygen-injured adults contained a 17-fold greater percentage of PMN and 16-fold higher protein than oxygen-exposed newborns. Hyperoxic adults had significantly lower 6-keto-PGF1a, and significantly higher LTB4 and LTC4 in BAL compared to hyperoxic newborns. This study confirms the hypothesis of relative oxygen tolerance in newborn rabbits compared to adults, and suggests that this tolerance may have been afforded by higher pulmonary levels of the protective prostacyclin metabolite.

Animals

Oleic acid lung injury increases plasma prostaglandin levels.

To determine whether lung injury causes increased plasma prostaglandin (PG) levels, 35 rabbits received oleic acid and 35 served as controls. Half of each group also received 4 ml/kg of Intralipid over one hour and at least five in each subgroup received indomethacin 7.5 mg/kg. Arterial and venous plasma concentrations of PGE2, 6-keto-PGF1 alpha, and PGF2 alpha-M were measured. Venous PGE2 was significantly higher in the oleic acid-injured than in the normal lung group, 1560 +/- 270 (Mean +/- SEM) versus 880 +/- 140 pg/ml (p less than .05). Plasma levels were reduced by 50% with indomethacin, but PGE2 levels remained significantly higher than in the normal lung group, 850 +/- 180 versus 480 +/- 60 for arterial (p less than .05) and 820 +/- 140 versus 480 +/- 80 for venous (p less than .05), respectively. PGF2 alpha-M levels were significantly higher in the lung injury group, 240 +/- 50 versus 50 +/- 40 pg/ml for arterial (p less than .05) and 220 +/- 50 versus 95 +/- 40 for venous (p less than .05), respectively. These lung injury-related increases in PGE2 and PGF2 alpha-M appear related both to increased pulmonary production and to decreased pulmonary clearance. With Intralipid infusion, however, arterial PGE2 increased by 500 +/- 260 pg/ml compared to baseline (p less than .05) with no change in venous PGE2, indicating in this instance that the increase in arterial PGE2 levels is related to increased pulmonary production.

Animals

Assessing validity of infant monitor alarms with event recording.

We evaluated the performance of an event recorder system in a large, consecutive series of referred monitored patients to determine the relative incidence of true apnea and true bradycardia, false alarms, and alarms for movement or a loose lead. In addition, we developed an event classification system based on the reason for the event being recorded. The recorder stored transthoracic impedance and electrocardiogram signals on a floppy disk before, during, and after each monitor alarm. These events on 302 disks from 83 patients were analyzed and classified as true, false, or movement-loose lead. Of 14,131 events, only 8% were caused by apnea or bradycardia (true events). Of true events, 70% were triggered by apnea and 30% by bradycardia. These true events occurred in 48% of the patients. False alarms constituted 23%, and movement-loose lead 69%, of all events. Even when movement-loose lead events were excluded, nearly three of four events were found to be false. Event recording proved helpful clinically, allowing discontinuation of the monitor in 49% of patients, modification of monitor alarm settings, or reassurance and counseling for parents.

Apnea

Prostaglandin E1 infusion fails to prevent hyperoxic lung injury in adult rabbits.

Arachidonic acid (AA) metabolites may be important mediators in the hyperoxic lung injury process. We have previously demonstrated, in an adult model of hyperoxic lung injury, that bronchoalveolar lavage (BAL) fluid levels of AA metabolites of the cyclooxygenase pathway increase before evidence of overt injury. Nonselective inhibition with indomethacin or dexamethasone failed to ameliorate the injury process, possibly because production of prostaglandin I2 (PGI2) was suppressed. In this study, we attempted to ameliorate hyperoxic lung injury using an infusion of prostaglandin E1 (PGE1), since PGE1 has some of the potentially protective effects of PGI2. Thirty-two adult rabbits were exposed to greater than 95% oxygen; eight served as controls and 24 received PGE1 infusion (five, nine, and ten received 0.1, 0.06, and 0.03 micrograms/kg.min, respectively). At the end of the 65-h exposure period, BAL of the left lung was performed; the right was saved for light microscopy. PGE1 infusion at the 0.06 and 0.03-micrograms/kg.min doses resulted in significantly fewer polymorphonuclear leukocytes (PMN) in BAL fluid (p less than .05). However, PGE1 infusion did not significantly ameliorate the lung injury process. In summary, although PGE1 infusion inhibited the influx of PMN into the lung, treatment did not result in any significant amelioration of the hyperoxic lung injury process.

Alprostadil