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Biomedical subjects

S L Ward

Publications and source records attributed to S L Ward.

At least 37 records · Page 2Linked to original sources
PubMed1994

Absent peripheral chemosensitivity in Prader-Willi syndrome.

Abnormalities in ventilatory control during wakefulness and sleep have been observed in patients with Prader-Willi syndrome (PWS). The role of peripheral chemoreceptors in the pathophysiology of abnormal ventilatory responses in PWS is unknown. We studied peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients [age 27.0 +/- 2.5 (SE) yr; 7 males, 10 females; body mass index 31.1 +/- 1.4 kg/m2] and compared their responses with 17 control subjects matched for age, sex, and body mass index. All PWS and control subjects had normal resting end-tidal PCO2 and arterial O2 saturation while awake. Peripheral chemoreceptor function was assessed by the ventilatory responses to 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. Control subjects decreased minute ventilation (VE) by 15.5 +/- 3.6% during hyperoxia. However, PWS patients increased VE by 17.6 +/- 3.3%, indicating a paradoxical response to hyperoxia (P < 0.00001). After CO2 vital capacity breaths, PWS patients showed no significant change and control subjects showed a marked increase (P < 0.0001) in VE. During N2 breathing, again PWS patients showed no change and control subjects exhibited a marked increase (P < 0.00005) in VE. We conclude that PWS patients have absent peripheral chemoreceptor ventilatory responses. We speculate that the lack of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers.

Adult↗
PubMed1994

Ventilatory responses during wakefulness in children with obstructive sleep apnea.

The pathophysiology of the obstructive sleep apnea syndrome (OSAS) is not fully understood. In children, airway obstruction secondary to tonsilloadenoidal hypertrophy is the leading cause of OSAS. However, not all children with tonsilloadenoidal hypertrophy develop OSAS. Thus, other factors, including abnormalities in ventilatory control, may contribute to the etiology of OSAS. To test this, we performed polysomnography and hypercapnic and hypoxic ventilatory response testing in 20 children and adolescents with OSAS (mean age, 8 +/- 3 [SD] yr) and 19 control subjects. Only two children with OSAS were obese. Children with OSAS had an apnea index of 16 +/- 20, peak PETCO2 of 54 +/- 5 mm Hg, and SaO2 nadir of 84 +/- 13% during polysomnography. Ventilatory responses were performed by rebreathing techniques. The slope of the hypercapnic ventilatory responses, corrected for body surface area, was 1.74 +/- 0.79 L/min/m2/mm Hg PETCO2 in children with OSAS and 1.45 +/- 0.58 L/min/m2/mmHg PETCO2 in control subjects (NS). Hypoxic ventilatory responses, corrected for body surface area, were -0.94 +/- 0.49 L/min/m2/% SaO2 in children with OSAS and -0.95 +/- 0.45 L/min/m2/% SaO2 in control subjects (NS); however, the sample size was small. There was a weak inverse correlation between the slope of the hypercapnic ventilatory response and the duration of hypoventilation during polysomnography (r = -0.44, p < 0.05). We conclude that children with OSAS have normal ventilatory responses to hypercapnia, and they may have normal ventilatory responses to hypoxia. We speculate that abnormal central ventilatory drive plays little if any role in the pathogenesis of pediatric OSAS.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoids↗
PubMed1993

Prevalence of medium-chain acyl-coenzyme A dehydrogenase deficiency in the sudden infant death syndrome.

Disorders of fatty acid beta-oxidation have been suggested as playing a significant role in the sudden infant death syndrome (SIDS). To elucidate the role of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency in SIDS, we identified all cases of SIDS occurring in Los Angeles County between January 1986 through December 1991. A total of 1304 SIDS deaths were identified; tissue samples were collected in 1236 cases (94.8%). Extraction of DNA was successful in 1224 tissue samples (93.9%), which were examined for the presence of the G985 mutation, identified as occurring in more than 88% of affected cases of MCAD deficiency. Three heterozygotes and no homozygotes were identified; this incidence does not differ from that reported in the general population. Review of the pathologic specimens from the identified heterozygotes and from 18 ethnic-, age-, and sex-matched control subjects revealed significant fatty infiltration of all organs examined in one of the three heterozygotes and in none of the control subjects. We conclude that MCAD deficiency does not play a significant role in the causation of SIDS.

Acyl-CoA Dehydrogenase↗
PubMed1993

Apnea spells, sudden death, and the role of the apnea monitor.

SIDS is the most common cause of death between the ages of 1 week and 1 year. It affects 1 out of every 500 to 600 live births. The etiology of SIDS is unknown. There are no tests currently available to predict the infant who will die from SIDS prior to death. SIDS cannot be prevented. Many infants experience serious apneic spells, however, that require diagnostic evaluation and treatment. Even if the treatment of these infants does not have a large impact on the SIDS rate for the general population, thorough diagnostic evaluations and appropriate use of home apnea-bradycardia monitoring is indicated for this population and may reduce their risk of morbidity or mortality.

Female↗
PubMed1993

Obstacles to discharge of ventilator-assisted children from the hospital to home.

Home care for ventilatory-assisted children improves psychosocial development and reduces medical costs compared with hospital care; yet, many ventilator-assisted children remain hospitalized for lengthy periods of time after they have achieved medical stability. To identify factors that contributed to a delay in hospital discharge from the time medical stability was achieved, we reviewed the records of 54 ventilator-assisted children (age 4.6 +/- 5.9 [SD] years at discharge) who were discharged from the hospital on a regimen of home mechanical ventilation. The length of the hospitalization from which the ventilator-assisted children were initially discharged on the ventilator was 172 +/- 161 days (range, 2 to 756). The time from medical stability to discharge was 118 +/- 144 days (range, 2 to 724), or 73 percent +/- 29 percent of the total hospitalization. Fifty-one ventilator-assisted children were discharged to their natural parents' homes, and three were discharged to foster care. Once ventilator-assisted children were medically stable, it took 99 +/- 141 days for third-party payers to approve home care funding, and only 48 +/- 87 days to be discharged once funding was approved. For the 27 ventilator-assisted children with public funding, it took 184 +/- 177 days for home care funding approval, compared with 52 +/- 43 days for the 27 ventilator-assisted children with private funding (p < 0.001). Parent training took only 52 +/- 65 days. It took 369 +/- 334 days (range, 44 to 711 days) to find placement for the three ventilator-assisted children who were placed in medical foster care. In summary, ventilator-assisted children often remained hospitalized for prolonged periods of time, after they were medically stable, for nonmedical reasons. The greatest obstacle to hospital discharge was seeking approval for home care funding and for arranging out-of-home placement. Public funding agencies took significantly longer to approve home care funding than private insurance agencies.

Adolescent↗
PubMed1992

Comparison of nap and overnight polysomnography in children.

Overnight polysomnography is the "gold standard" for diagnosing sleep-disordered breathing. However, the limited number of resources for pediatric polysomnography make the availability of a screening test for sleep-disordered breathing highly desirable. Therefore, we compared 1 hour daytime nap polysomnography to overnight polysomnography in 40 children [mean age, 5.4 +/- 0.8 (SE) years] with sleep-disordered breathing; 76% of children were sedated with chloral hydrate for nap polysomnography; none was sedated for overnight polysomnography. Studies were done 26 +/- 4 days apart. Chest wall motion, ECG, end-tidal PCO2 (PETCO2), arterial oxygen saturation (SaO2), and electrooculogram were monitored. Nap studies had a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 17% in predicting sleep-disordered breathing. Significantly more children had obstructive apnea and desaturation (SaO2 less than 90%) during overnight polysomnography. The peak PETCO2 and the SaO2 nadir were significantly worse during overnight polysomnography. However, the percentage of time during which abnormalities were manifested did not differ between nap and overnight polysomnography. Despite the use of sedation, nap polysomnography underestimated sleep-disordered breathing. We conclude that sleep-disordered breathing detected by nap polysomnography is always confirmed by overnight polysomnography and speculate that nap polysomnography may be an effective screening method for sleep-disordered breathing. However, overnight polysomnography should be performed if nap polysomnography is inconclusive. Chloral hydrate may be used effectively to facilitate sleep for nap polysomnography in children.

Adolescent↗
PubMed1992

A calcium-binding monoclonal antibody that recognizes a non-calcium-binding epitope in the short consensus repeat units (SCRs) of complement C1r.

C1r is a Ca(2+)-binding serine protease that interacts with two other plasma proteins, C1q and C1s, to form C1, the first component of the complement cascade. A monoclonal antibody, BG6, has been produced which binds to C1r only in the presence of Ca2+, requiring 3-5 microM Ca2+ for half-maximal binding. The antibody reacts with native and heat-denatured C1r, and with zymogen C1r, but does not cross-react with C1s or C1q. BG6 did not significantly affect the esterolytic activity of C1r toward a synthetic thioester substrate nor the hemolytic activity of C1 reconstituted from subcomponents in the presence of the antibody. A tryptic fragment of C1r which consists of the C-terminal gamma region of the A chain disulfide-linked to the B chain (gamma B) binds in a Ca(2+)-dependent manner to BG6-Sepharose. Western blotting experiments have further localized the epitope to the gamma region of the A chain, which is composed of two short consensus repeat (SCR) units. The N-terminal alpha region contains the only previously determined Ca(2+)-binding site in the C1r molecule. Equilibrium dialysis experiments confirmed that C1r-gamma B does not bind Ca2+, and showed that antibody BG6 and the gamma B/BG6 complex do bind Ca2+. Thus, the Ca(2+)-dependent nature of this interaction is due exclusively to binding of the metal ion to the antibody. Equilibrium dialysis and immunoblotting have further localized the Ca(2+)-binding site to the Fab fragment of BG6, indicating that the metal-induced conformational change residues in or near the variable region of the IgG. BG6 may set a precedent for the preparation of Ca(2+)-dependent antibodies to non-Ca(2+)-binding epitopes in other proteins.

Antibodies, Monoclonal↗
PubMed1992

Hypercapnic and hypoxic ventilatory and cardiac responses in school-aged siblings of sudden infant death syndrome victims.

Siblings of sudden infant death syndrome (SIDS) victims have been shown to have abnormal ventilatory patterns and altered responses to respiratory stimuli during infancy. To evaluate whether these abnormalities persist, we studied ventilatory responses in 20 older SIDS siblings (9.8 +/- 0.9 (mean +/- SEM) years of age) and 20 control subjects (10.2 +/- 0.9 years of age). To evaluate hypercapnic ventilatory responses, we had subjects rebreathe 5% carbon dioxide and 95% oxygen until end-tidal carbon dioxide tension reached 65 mm Hg. Instantaneous minute ventilation, mean inspiratory flow, and respiratory rate were calculated breath by breath. Hypercapnic responses did not differ between SIDS siblings (2.08 +/- 0.14 L/min per mm Hg) and control subjects (1.90 +/- 0.10 L/min per mm Hg; not significant). To assess hypoxic ventilatory responses, we asked subjects to rebreathe 13% oxygen and 7% carbon dioxide, with the balance nitrogen, at mixed-venous end-tidal carbon dioxide tension, until arterial oxygen saturation by pulse oximetry fell to 75%. No differences in hypoxic ventilatory responses were found between the SIDS siblings (-1.39 +/- 0.15 L/min/% saturation) and the control subjects (-1.22 +/- 0.17 L/min/% saturation; not significant). The mean inspiratory flow, tidal volume, respiratory rate, and heart rate responses to hypercapnia and hypoxia were also similar in the two groups. We conclude that there is no difference in hypercapnic and hypoxic ventilatory and cardiac responses, as assessed by rebreathing techniques, between school-aged SIDS siblings and control subjects. We speculate that in SIDS siblings the control of breathing is immature during infancy and that they achieve maturity of control and resolution of breathing abnormalities with time.

Child↗
PubMed1992

Responses to hypoxia and hypercapnia in infants of substance-abusing mothers.

Because infants of substance-abusing mothers (ISAM) have an increased risk of sudden infant death syndrome and have abnormal sleeping ventilatory patterns, we studied the effects of mild hypoxia during quiet sleep on ventilatory pattern, heart rate, and arousal in 23 healthy ISAM (mean +/- SEM: 9.0 +/- 0.49 weeks of age) and 15 healthy, similarly aged, control infants. Hypercapnic challenges were performed in six ISAM and eight control subjects. Hypoxic arousal responses were elicited by rapidly decreasing inspired oxygen tension to 80 mm Hg for 3 minutes or until arousal occurred. Failure to arouse to hypoxia occurred in the majority of infants in both groups. All infants had a fall in end-tidal carbon dioxide tension during hypoxia, suggesting that each had a hypoxic ventilatory response. However, the fall in end-tidal carbon dioxide tension was significantly less in the ISAM (mean +/- SEM: -4.0 +/- 0.3 vs -8.0 +/- 1.0 mm Hg), suggesting blunted ventilatory responses to hypoxia. Periodic breathing occurred during 9.5% of hypoxic challenges in control infants compared with 37% in ISAM (p = 0.056). Heart rates were significantly higher in the ISAM before, during, and after hypoxic challenges. Hypercapnic challenges (inspired carbon dioxide tension of 60 mm Hg for a maximum of 3 minutes) resulted in arousal in all infants; however, ISAM required a significantly longer exposure to hypercapnia before arousal (mean +/- SEM; 116 +/- 7.8 vs 79 +/- 13.9 seconds; p < 0.02). We conclude that ISAM have an impaired repertoire of protective responses to hypoxia and hypercapnia during sleep, and that this may play a role in their increased risk for sudden infant death syndrome.

Arousal↗
PubMed1992

Normal polysomnographic values for children and adolescents.

Although polysomnography is routinely performed to evaluate children and adolescents with sleep-disordered breathing, normal polysomnographic values for the pediatric age group have not yet been established. We therefore performed overnight polysomnography in 50 normal children and adolescents (mean age 9.7 +/- 4.6 SD yr, range 1.1 to 17.4 yr). Of the children 56% were male. Chest wall motion, ECG, oronasal airflow, end-tidal PCO2 (PETCO2), arterial oxygen saturation (SaO2), and electrooculogram were monitored. Children had 0.1 +/- 0.5 (range 0 to 3.1) obstructive apneas per hour of total sleep time, with only 18% of children having any obstructive apneas. No child had obstructive apneas > 10 s in duration. Of the children 30% had central apneas > or = 10 s in duration, and one child had a central apnea associated with SaO2 < 90%. Peak PETCO2 was 46 +/- 4 mm Hg (range 38 to 53 mm Hg), and hypoventilation (PETCO2 > 45 mm Hg) occurred for 7 +/- 19% total sleep time (range 0 to 91%). The SaO2 nadir was 96 +/- 2% (range 89 to 98%), with only one child desaturating below 90% in association with a central apnea. We conclude that polysomnographic results in the pediatric age group differ from those in adults. Recommendations for normal polysomnographic criteria are given.

Adolescent↗
PubMed1992

Theophylline does not increase ventilatory responses to hypercapnia or hypoxia.

Theophylline is commonly believed to stimulate central respiratory centers. We studied the effect of oral theophylline therapy on ventilatory responses to hypercapnia and hypoxia during a double-blind placebo-controlled trial with a slow release oral theophylline preparation. We measured hypercapnic and hypoxic ventilatory responses using rebreathing techniques in 15 subjects (21 to 41 yr of age, with normal lung function) on three occasions: baseline, after 4 days of Drug 1, and after 4 days of Drug 2. For subjects receiving theophylline, the mean serum theophylline level was 11.3 + 1.3 (SE) micrograms/ml (range, 5.3 to 22.1). Unpleasant side effects were reported by 11 of the 15 subjects (nausea, jitteriness, and agitation) while receiving theophylline but not while receiving placebo. The mean hypercapnic ventilatory response with placebo was 4.3 +/- 0.9 L/min/mm Hg PACO2 and with theophylline it was 4.5 +/- 0.7 L/min/%SaO2 and with theophylline it was -2.7 +/- 0.4 L/min/%SaO2. Hypoxic responses for each subject were measured at similar PvCO2. There were no significant changes in ventilatory responses with theophylline. We conclude that theophylline use, at a dose sufficient to cause side effects, does not affect chemoreceptor responsiveness.

Adult↗
PubMed1992

Prenatal substance abuse.

It has been reported that ISAM have an increased risk of SIDS and abnormalities of cardiorespiratory physiology. Abnormalities of cardiorespiratory control may account for the increased SIDS risk in some ISAM, and home monitoring is often used for ISAM with clinical apneic episodes. However, it is possible that the increased SIDS risk factors concentrated in this population. The increased SIDS risk SIDS risk factors concentrated in this population. The increased SIDS risk demonstrated in ISAM does not necessarily indicate that drug exposure during gestation in itself causes SIDS. Thus home monitoring is not indicated for ISAM who do not have apnea or other clinical evidence of a respiratory control abnormality.

Cocaine↗
PubMed1992

Hypoxic arousal responses in normal infants.

Failure to arouse in response to hypoxia has been described in infants at increased risk for sudden infant death syndrome (SIDS) and has been suggested as a possible mechanism for SIDS. However, most SIDS victims are not in a high-risk group before death. Thus, if a hypoxic arousal disorder is an important contributor to SIDS, normal infants might fail to arouse from sleep in response to hypoxia. To test this hypothesis, the authors studied hypoxic arousal responses in 18 healthy term infants younger than 7 months of age (age 12.1 +/- 1.7 [SEM] weeks; 56% girls). Hypoxic arousal challenges were performed during quiet sleep by rapidly decreasing inspired oxygen tension (PIO2) to 80 mm Hg for 3 minutes or until arousal (eye opening, agitation, and crying) occurred. Tests were performed in duplicate when possible. Only 8 infants (44%) aroused in response to one or more hypoxic challenges; arousal occurred during 8 (32%) of 25 trials. There were no significant differences in lowest PIO2 or arterial oxygen saturation during hypoxia between those infants who aroused and those who failed to arouse. All 18 infants had a fall in their end-tidal carbon dioxide tension during hypoxia, suggesting that each had a hypoxic ventilatory response despite failure to arouse in the majority. Periodic breathing occurred following hypoxia in only 1 (13%) of the 8 trials that resulted in arousal, compared with 16 (94%) of 17 trials without arousal (P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Apnea↗
PubMed1991

Obstructive sleep apnea in children with Down syndrome.

Children with Down syndrome have many predisposing factors for the obstructive sleep apnea syndrome (OSAS), yet the type and severity of OSAS in this population has not been characterized. Fifty-three subjects with Down syndrome (mean age 7.4 +/- 1.2 [SE] years; range 2 weeks to 51 years) were studied. Chest wall movement, heart rate, electroculogram, end-tidal PO2 and PCO2, transcutaneous PO2 and PCO2, and arterial oxygen saturation were measured during a daytime nap polysomnogram. Sixteen of these children also underwent overnight polysomnography. Nap polysomnograms were abnormal in 77% of children; 45% had obstructive sleep apnea (OSA), 4% had central apnea, and 6% had mixed apneas; 66% had hypoventilation (end-tidal PCO2 greater than 45 mm Hg) and 32% desaturation (arterial oxygen saturation less than 90%). Overnight studies were abnormal in 100% of children, with OSA in 63%, hypoventilation in 81%, and desaturation in 56%. Nap studies significantly underestimated the presence of abnormalities when compared to overnight polysomnograms. Seventeen (32%) of the children were referred for testing because OSAS was clinically suspected, but there was no clinical suspicion of OSAS in 36 (68%) children. Neither age, obesity, nor the presence of congenital heart disease affected the incidence of OSA, desaturation, or hypoventilation. Polysomnograms improved in all 8 children who underwent tonsillectomy and adenoidectomy, but they normalized in only 3. It is concluded that children with Down syndrome frequently in have OSAS, with OSA, hypoxemia, and hypoventilation. Obstructive sleep apnea syndrome is seen frequently in those children in whom it is not clinically suspected. It is speculated that OSAS may contribute to the unexplained pulmonary hypertension seen in children with Down syndrome.

Adenoidectomy↗
PubMed1991

Elevated plasma norepinephrine levels in infants of substance-abusing mothers.

Infants of substance-abusing mothers (ISAM) have significant growth and neurodevelopmental abnormalities. The origin of these abnormalities is unknown. We postulated that ISAM have increased sympathetic nervous system tone and altered catecholamine levels. Therefore, we measured plasma norepinephrine, epinephrine, and dopamine levels and the number and receptor affinity of beta-adrenoreceptor binding sites on lymphocytes and alpha-adrenoreceptor binding sites on thrombocytes in 22 otherwise healthy ISAM (age, 2.1 +/- 0.5 months; mean +/- SD) and 15 healthy controls (age, 2.5 +/- 0.8 months). Norepinephrine levels in venous blood were 1.8-fold higher in ISAM than in control infants (6.30 +/- 3.85 nmol/L vs 3.55 +/- 2.45 nmol/L). There were no differences in plasma epinephrine or dopamine levels. There were no differences in the number of binding sites or receptor affinity for beta- and alpha-adrenoreceptors. We conclude that ISAM have elevated circulating norepinephrine levels compared with controls. We speculate that this is associated with increased sympathetic nervous system tone in ISAM and that the absence of adrenoreceptor down-regulation may create catecholamine suprasensitivity.

Blood Platelets↗
PubMed1991

Hypercapneic arousal responses in children with congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is generally thought to be due to insensitivity of the central chemoreceptors to carbon dioxide. Children with CCHS have absent ventilatory responses to both hypercapnea and hypoxia, suggesting either abnormal central and peripheral chemoreceptor function or abnormal central integration of chemoreceptor input. Because ventilatory and arousal responses to respiratory stimuli are distinct from each other, if children with CCHS have complete chemoreceptor dysfunction, one would predict that both ventilatory and arousal responses to respiratory stimuli would be abnormal. However, if they have abnormal central integration of chemoreceptor input for ventilation, they may still arouse to respiratory stimuli despite the absence of a ventilatory response. Hypercapneic arousal responses were tested in eight children with CCHS, aged 5.8 +/- 1.2 (SEM) years, and seven healthy control subjects, aged 4.4 +/- 1.1 years. Children were studied during sleep while normal ventilation was maintained using their home ventilators. Hypercapneic challenges were performed by rapidly increasing the inspired carbon dioxide tension to 60 mm Hg and maintaining this level until the child aroused or for a maximum of 3 minutes. Of children with CCHS, 87.5% aroused to hypercapnea, compared with 100% of control children. There was no significant difference in arousal between children with CCHS and normal control subjects. It is concluded that most children with CCHS arouse to hypercapnea, indicating the presence of some central chemoreceptor function. It is speculated that because these children do respond to hypercapnea, the most probable mechanism for CCHS is a brainstem lesion in the area where input from both chemoreceptors is integrated.

Arousal↗
PubMed1991

Cardiac pacemaker in high spinal cord injury.

Bradycardia followed by cardiac arrest is well documented as a complication of acute injury to the cervical spinal cord. This life-threatening bradycardia is attributed to an imbalance in the autonomic nervous system resulting from dissociation of the parasympathetic from the sympathetic responses during the stage of spinal shock. A patient with a C2 complete quadriplegia secondary to birth trauma who experienced symptomatic bradycardia, continuing for 21 months after injury despite intensive medical management, is reported. Clinical improvement followed insertion of a cardiac pacemaker. Possible etiologies for the continuation of abnormal bradycardia episodes after the resolution of spinal shock are discussed. Cardiac pacemaker implantation is advocated for patients with high cervical spinal cord injuries and continuing symptomatic bradycardia not responding to medical measures.

Birth Injuries↗