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Biomedical subjects

C E Hunt

Publications and source records attributed to C E Hunt.

At least 37 records · Page 2Linked to original sources
PubMed1995

Induction of a hepatic toxic syndrome in the Dutch-belted rabbit by a quinoxalinone anxiolytic.

The non-benzodiazepine anxiolytic, panadiplon, was discontinued from clinical development due to evidence of hepatic toxicity in human volunteers that was not predicted by rat or monkey preclinical development studies. The present study was conducted to examine potential toxicity in the rabbit. Three groups of female rabbits were administered vehicle, 10 mg/kg per day or 20 mg/kg per day of panadiplon by oral gavage for 14 days. Animals in the 20 mg/kg group lost weight, and 6/10 developed a profound lethargy. Hepatic toxicity was observed in treated animals, evidenced by dose- and time-related increases in serum transaminase activities, gross hepatic lesions and multifocal centrilobular necrosis. Hepatic microvesicular steatosis was evident in treated animals; lipid analysis revealed a 123% increase in hepatic triglyceride. A time-dependent increase in serum triglyceride levels was observed in the high-dose group beginning on day 4. Hepatic glycogen was reduced, and histochemical examination revealed the reduction to be heterogeneous across the lobule with some areas showing a complete absence of glycogen. One rabbit in each drug-treated group showed mild hypoglycemia at day 12, and 4/10 rabbits in the high-dose group showed hyperglycemia at days 12-14. We conclude that panadiplon produced a microvesicular steatosis and hepatic toxicity in the rabbit. The observed toxicity resembled a Reye's syndrome-like toxicity produced by a variety of mitochondrial fatty acid oxidation inhibitors.

Animals↗
PubMed1995

Assessment of compliance with home cardiorespiratory monitoring in infants at risk of sudden infant death syndrome. Collaborative Home Infant Monitoring Evaluation (CHIME).

OBJECTIVES: Documented monitoring was used to evaluate prospectively (1) the level of compliance among infants in whom cardiorespiratory monitoring was clinically indicated and (2) factors that might influence compliance: diagnosis, socioeconomic status, maternal age and education, and alarms. STUDY DESIGN: Sixty-seven infants (51% female, 49% term) were sequentially enrolled, and monitoring was prescribed for the following indications: siblings of sudden infant death syndrome victims (16%), apnea of prematurity (45%), and apparent life-threatening events or apnea of infancy (39%). Demographic data, alarm and event data, and a summary report of monitor use from the first monitor download were obtained. RESULTS: Maternal age, education, and insurance status did not differ significantly by indication for monitoring. The median number of monitor alarms per 10 hours of use was 0.7 for apnea or bradycardia and 0.6 for loose lead alarms. Monitors were available for use in the home from 2 to 106 days (median, 11 days). Median hours of monitor use per full day in the home was 15.5 hours. Of 67 infants, 58 used the monitor for at least part of every day in the home. The number of hours of monitor use per day did not differ significantly by diagnostic category, chronologic age, alarms, maternal age, education, or insurance type. This study population of infants at increased risk of sudden infant death syndrome had excellent compliance; 75% of the infants were monitored more than 10.5 hours per day, and 25% were monitored more than 21 hours per day. CONCLUSIONS: Documented monitoring provides an objective measure of compliance. These data provide a potential goal for level of compliance with home cardiorespiratory monitoring.

Analysis of Variance↗
PubMed1995

A community-based survey of infant sleep position. Pediatric Research in Office Practices Network.

OBJECTIVE: To determine prevalent infant sleep positions before and after the American Academy of Pediatrics position statement of 1992 and to identify determinants of sleep position. METHOD DESIGN: cross-sectional survey. SETTING: private and hospital-sponsored general pediatric offices. PARTICIPANTS: parents of infants younger than 7 months of age. RESULTS: Eight hundred fifty-two care givers completed surveys during the 5-week study. Fifty-four percent of the study infants were put to sleep in the prone position. In 416 families with more than one child, however, 75% of the youngest siblings had been put to sleep in the prone position at the same age. Gender, race, family income, maternal smoking, and birth weight were not associated with choice of sleep position. CONCLUSIONS: There has been a change in infant sleep positioning in the desired direction since the American Academy of Pediatrics statement. However, 54% of the study infants were still being put to sleep prone.

Age Factors↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗