PubMed Health⌕ Search

Biomedical subjects

H Lester Kirchner

Publications and source records attributed to H Lester Kirchner.

At least 37 records · Page 2Linked to original sources

The effects of age, sex, ethnicity, and sleep-disordered breathing on sleep architecture.

BACKGROUND: Polysomnography is used to assess sleep quality and to gauge the functional effect of sleep disorders. Few population-based data are available to estimate the variation in sleep architecture across the population and the extent to which sleep-disordered breathing (SDB), a common health condition, contributes to poor sleep independent of other factors. The objective of this study was to describe the population variability in sleep quality and to quantify the independent associations with SDB. METHODS: Cross-sectional analyses were performed on data from 2685 participants, aged 37 to 92 years, in a community-based multicenter cohort study. Dependent measures included the percentage time in each sleep stage, the arousal index, and sleep efficiency. Independent measures were age, sex, ethnicity, comorbidity status, and the respiratory disturbance index. RESULTS: Lighter sleep was found in men relative to women and in American Indians and blacks relative to other ethnic groups. Increasing age was associated with impaired sleep in men, with less consistent associations in women. Notably, women had, on average, 106% more slow wave sleep. Sleep-disordered breathing was associated with poorer sleep; however, these associations were generally smaller than associations with sex, ethnicity, and age. Current smokers had lighter sleep than ex-smokers or never smokers. Obesity had little effect on sleep. CONCLUSIONS: Sleep architecture varies with sex, age, ethnicity, and SDB. Individual assessment of the effect of SDB on sleep quality needs to account for other host characteristics. Men, but not women, show evidence of poorer sleep with aging, suggesting important sex differences in sleep physiology.

Adult↗

Variation in childhood asthma among former preterm infants.

OBJECTIVES: The role of in utero and perinatal exposures in modifying asthma risk among children born prematurely was assessed. Study design Former preterm children (n=251) were identified from a birth cohort. Examinations, including lung function testing, were performed at ages 8 to 11 years. Perinatal exposures were ascertained from neonatal medical records. RESULTS: Univariate predictors of asthma included male gender, African American ethnicity, maternal asthma, and birth weight. Asthmatics were less likely to have been small for gestational age (SGA) than nonasthmatics (12.4% vs 22.7%, P=.04) and had more neonatal pulmonary disease. After adjusting for maternal asthma and demographic factors, asthma was associated with chronic lung disease of infancy, neonatal mechanical ventilation and corticosteroid use, and a higher childhood body mass index. Children who were septic postbirth and girls who were SGA were less likely to have asthma (OR for sepsis, 0.2; 95% CI, 0.1-0.6; OR for girls who were SGA compared with girls who were not SGA, 0.05; CI, 0.01-0.34). CONCLUSIONS: Among premature children, female SGA status and neonatal sepsis appear protective relative to the development of childhood asthma. Differential susceptibility to asthma among preterm children may relate to exposures that operate in the in utero and early postnatal environment to accelerate lung development, alter innate immunity, or both.

Asthma↗

Increased behavioral morbidity in school-aged children with sleep-disordered breathing.

OBJECTIVE: To assess whether sleep-disordered breathing (SDB), ranging from primary snoring to obstructive sleep apnea (OSA), is associated with increased behavioral morbidity. METHODS: A cross-sectional study was conducted of school-aged children in an urban, community-based cohort, stratified for term or preterm (<37 weeks' gestation) birth status. A total of 829 children, 8 to 11 years old (50% female, 46% black, 46% former preterm birth) were recruited from a cohort study. All children had unattended in-home overnight cardiorespiratory recordings of airflow, respiratory effort, oximetry, and heart rate for measurement of the apnea hypopnea index (number of obstructive apneas and hypopneas per hour). SDB was defined by either parent-reported habitual snoring or objectively measured OSA. Functional outcomes were assessed with 2 well-validated parent ratings of behavior problems: the Child Behavioral Checklist and the Conners Parent Rating Scale-Revised:Long. RESULTS: Forty (5%) children were classified as having OSA (median apnea hypopnea index: 7.1 per hour; interquartile range: 3.1-10.5), 122 (15%) had primary snoring without OSA, and the remaining 667 (80%) had neither snoring nor OSA. Children with SDB had significantly higher odds of elevated problem scores in the following domains: externalizing, hyperactive, emotional lability, oppositional, aggressive, internalizing, somatic complaints, and social problems. CONCLUSIONS: Children with relatively mild SDB, ranging from primary snoring to OSA, have a higher prevalence of problem behaviors, with the strongest, most consistent associations for externalizing, hyperactive-type behaviors.

Attention Deficit and Disruptive Behavior Disorder↗

Effect of ibuprofen on neutrophil migration in vivo in cystic fibrosis and healthy subjects.

Long-term treatment with ibuprofen twice daily, at doses that achieve peak plasma concentration (Cmax) >50 microg/ml, slows progression of lung disease in patients with cystic fibrosis (CF). Previous data suggest that Cmax >50 microg/ml is associated with a reduction in neutrophil (PMN) migration into the lung and that lower concentrations are associated with an increase in PMN migration. To estimate the threshold concentration at which ibuprofen is associated with a decrease in PMN migration in vivo, we measured the PMN content of oral mucosal washes in 35 healthy (age 19-40 years) and 16 CF (age 18-32 years) subjects who took ibuprofen twice daily for 10 days in doses that achieved Cmax 8 to 90 microg/ml. Cmax >50 microg/ml was associated with a 31 +/- 7% (mean +/- S.E.M.) reduction in PMNs in CF (n = 11, p < 0.001) and 25 +/- 6% reduction in PMNs in healthy subjects (n = 16, p < 0.001). Increasing concentrations above 50 microg/ml was not associated with a greater decrease in PMNs. The reduction in PMN migration was consistently present 12 h after a dose, but not after 24 h. Cmax <50 microg/ml was associated with an increase in PMNs of approximately 40%. These results suggest that Cmax >50 microg/ml and twice daily dosing of ibuprofen are required to decrease PMN migration, and reinforce the current recommendation that pharmacokinetics should be performed in CF patients prescribed ibuprofen.

Anti-Inflammatory Agents, Non-Steroidal↗

Significant variation in serotype-specific immunogenicity of the seven-valent Streptococcus pneumoniae capsular polysaccharide-CRM197 conjugate vaccine occurs despite vigorous T cell help induced by the carrier protein.

Streptococcus pneumoniae capsular polysaccharides (PnPSs) induce protective antibodies but are T cell-independent type 2 antigens and are poorly immunogenic in infants. Conjugate vaccines of PnPSs linked to proteins like cross-reactive material (CRM(197)) increase PS antibody titer and elicit immunologic memory in infants. Despite being linked to an identical carrier protein, each PS component of the 7-valent PnPS-CRM(197) vaccine has different immunogenicity. To determine whether variations in conjugate-induced memory T cell responses or PnPS-specific antibody-secreting cells (ASCs) were responsible for serotype-specific differences in immunogenicity, adults were immunized with 7-valent PnPS-CRM(197), and antibody titer, vaccine component-specific CD4(+) T cell recall response, numbers of PnPS-specific ASCs, and cytokine production were measured. PnPS-CRM(197) induced significantly different serotype-specific antibody titers, despite vigorous T cell recall responses to all 7 vaccine components, and production of interleukin (IL)-2, IL-5, IL-6, IL-10, and interferon-gamma. We conclude that PnPS-CRM(197) induces variable serotype-specific antibody titers, despite induction of comparable CRM(197)-specific memory T cell responses.

Adult↗

Does using heat with eutectic mixture of local anesthetic cream shorten analgesic onset time? A randomized, placebo-controlled trial.

STUDY OBJECTIVES: We determine whether the addition of heat to topical eutectic mixture of local anesthetic (EMLA) cream shortens the onset time to effective analgesia. We hypothesized that applying EMLA cream for 20 minutes with an external heat pack would be as effective as the standard 60-minute application time. METHODS: In this prospective, double-blind study using adult volunteers, research subjects were randomized into groups undergoing either 20 minutes or 60 minutes of EMLA cream application time. Each research subject underwent randomized cream application over both hands and wrists in the following manner: EMLA cream with heat, EMLA cream without heat, placebo with heat, and placebo without heat. Research subjects then underwent a single attempt at intravenous catheterization over each of the 4 sites and scored the degree of pain using a 100-mm visual analog scale. RESULTS: Seventy-six research subjects were enrolled: 39 were randomized to the 20-minute group, and 37 were randomized to the 60-minute group. EMLA cream applied for 20 minutes with heat (adjusted mean visual analog scale score of 31.9 mm) provided statistically and clinically significantly greater analgesia compared with that seen in the placebo groups with or without heat (46.6 and 46.1 mm, respectively), with estimated differences of -14.6 (95% confidence interval [CI] -21.2 to -8.1) and -14.1 (95% CI -20.8 to -7.3), respectively. However, applying EMLA cream for 60 minutes without heat (16.6 mm) provided better analgesia compared with that seen after 20 minutes of EMLA cream with heat (31.9 mm; estimated difference of -15.4 [95% CI -25.1 to -5.6]). CONCLUSION: Applying EMLA cream for 20 minutes with heat provides intermediate analgesia for intravenous catheter placement, although 60 minutes of application time remains superior.

Adult↗

Prevalence and risk factors for sleep-disordered breathing in 8- to 11-year-old children: association with race and prematurity.

OBJECTIVES: To evaluate the extent to which sleep-disordered breathing (SDB) varies with putative demographic and medical risk factors and to estimate the prevalence of undiagnosed SDB. STUDY DESIGN: Prospective, cross-sectional study in a population-based cohort of 850 children (41% black, 46% preterm), 8 to 11 years of age. Participants' caretakers completed questionnaires about health and sleep. Children underwent overnight in-home cardiorespiratory recordings of airflow, respiratory effort, oximetry, and electrocardiography. SDB was identified by respiratory disturbance indices commonly applied in clinical practice. Risk factors were estimated by logistic regression. Prevalence was derived from cohort-specific estimates with birth weights from US live births data. RESULTS: Using the most inclusive definition, SDB was detected in 40 (4.7%) participants, with prevalence varying widely across population subsets. Depending on the definition used, SDB was 4 to 6 times more likely in black children compared with white children and almost 3 to 5 times more likely in former preterm compared with term children. The estimated population prevalence of SDB was 2.2% (95% CI, 1.2%, 3.2%). CONCLUSIONS: SDB is a relatively common condition in 8- to 11-year-old children. Potentially vulnerable subgroups, black children, and former preterm infants, are at increased risk.

Cardiovascular System↗

Comparison of racemic albuterol and levalbuterol for treatment of acute asthma.

OBJECTIVE: To determine whether levalbuterol resulted in fewer hospital admissions than racemic albuterol when used for treatment of acute asthma. Study design A randomized, double-blind, controlled trial was conducted in the emergency department (ED) and inpatient asthma care unit of an urban tertiary children's hospital. Children age 1 to 18 years (n=482) provided a total of 547 enrollments. Patients received a nebulized solution of either 2.5 mg racemic albuterol or 1.25 mg levalbuterol every 20 minutes (maximum six doses). Patients admitted to the asthma care unit were treated in a standardized fashion by using the same blinded drug assigned in the ED. Hospitalization rate was the primary outcome. RESULTS: Hospitalization rate was significantly lower in the levalbuterol group (36%) than in the racemic albuterol group (45 %, P=.02). The adjusted relative risk of admission in the racemic group compared with the levalbuterol group was 1.25 (95% confidence interval, 1.01-1.57). Hospital length of stay was not significantly shorter in the levalbuterol group (levalbuterol, 44.9 hours; racemic albuterol, 50.3 hours; P=.63). No significant adverse events occurred in either group. CONCLUSIONS: Substituting levalbuterol for racemic albuterol in the ED management of acute asthma significantly reduced the number of hospitalizations.

Acute Disease↗

Predicting attrition in a pediatric asthma intervention study.

OBJECTIVES: To operationalize a comprehensive description of attrition, including pre-inclusion, dropout, and attrition due to intermittent missing data, and to test a predictive model of attrition using a data set from a randomized controlled intervention in pediatric asthma. METHODS: Participants included children, ages 4-12, diagnosed with asthma and their caregivers. Demographic variables and outcome measures of asthma morbidity were examined in 327 families to determine their association with attrition. RESULTS: Families who did not complete randomization and the intervention tended to have younger caregivers than did completers. Caregiver age emerged as the most consistent predictor of pre-inclusion and dropout attrition. There were no significant predictors of attrition due to intermittent missing data. CONCLUSION: Younger caregivers may be at particular risk for attrition in pediatric asthma intervention studies and warrant special attention by investigators.

Asthma↗

The prevalence of periodontal disease measures in elderly adults, aged 79 and older.

From 1996-98, we examined 449 adults (mean age 85 years) from the 1982 Iowa 65+ Rural Health Study, in the field using headlight, mirror, and periodontal probe. Ninety-six of the 342 dentate subjects were excluded from the follow-up examination due to contraindications to probing, and 10 could not be assessed due to refusals, fatigue or other reasons. For all remaining subjects (n=236), attachment loss, defined as recession plus probing depth, was determined at four sites per tooth. Ninety-one percent of the subjects had at least one site with 4+ mm of attachment loss, 45% had one or more sites with attachment loss of 6+ mm, and 15% had 8+ mm of attachment loss. Moderate periodontal disease is prevalent among very old dentate adults while advanced periodontal disease is much less prevalent, suggesting that most periodontal treatment needed by this age group can be provided by general dentists and dental hygienists rather than periodontists.

Aged↗

Simultaneous estimation of intrarater and interrater agreement for multiple raters under order restrictions for a binary trait.

It is valuable in many studies to assess both intrarater and interrater agreement. Most measures of intrarater agreement do not adjust for unequal estimates of prevalence between the separate rating occasions for a given rater and measures of interrater agreement typically ignore data from the second set of assessments when raters make duplicate assessments. In the event when both measures are assessed there are instances where interrater agreement is larger than at least one of the corresponding intrarater agreements. This implies that a rater agrees less with him/herself and more with another rater. In the situation of multiple raters making duplicate assessments on all subjects, the authors propose properties for an agreement measure based on the odds ratio for a dichotomous trait: (i) estimate a single prevalence across two reading occasions for each rater; (ii) estimate pairwise interrater agreement from all available data; (iii) bound the pairwise interrater agreement above by the corresponding intrarater agreements. Estimation of odds ratios under these properties is done by maximizing the multinomial likelihood with constraints using generalized log-linear models in combination with a generalization of the Lemke-Dykstra iterative-incremental algorithm. An example from a mammography examination reliability study is used to demonstrate the new method.

Algorithms↗

Cognitive and motor outcomes of cocaine-exposed infants.

CONTEXT: Maternal use of cocaine during pregnancy remains a significant public health problem, particularly in urban areas of the United States and among women of low socioeconomic status. Few longitudinal studies have examined cocaine-exposed infants, however, and findings are contradictory because of methodologic limitations. OBJECTIVE: To assess the effects of prenatal cocaine exposure on child developmental outcomes. DESIGN: Longitudinal, prospective, masked, comparison birth cohort study with recruitment in 1994-1996. SETTING: Obstetric unit of a large US urban teaching hospital. PARTICIPANTS: Four hundred fifteen consecutively enrolled infants (218 cocaine-exposed and 197 unexposed) identified from a high-risk, low-socioeconomic status, primarily black (80%) population screened through clinical interview and urine and meconium samples for drug use. The retention rate was 94% at 2 years of age. MAIN OUTCOME MEASURES: The Bayley Mental and Motor Scales of Infant Development, assessed at 6.5, 12, and 24 months of corrected age. RESULTS: Controlled for confounding variables, cocaine exposure had significant effects on cognitive development, accounting for a 6-point deficit in Bayley Mental and Motor Scales of Infant Development scores at 2 years, with cocaine-exposed children twice as likely to have significant delay (mental development index <80) (odds ratio, 1.98; 95% confidence interval, 1.21-3.24; P =.006). For motor outcomes, there were no significant cocaine effects. CONCLUSIONS: Cocaine-exposed children had significant cognitive deficits and a doubling of the rate of developmental delay during the first 2 years of life. Because 2-year outcomes are predictive of later cognitive outcomes, it is possible that these children will continue to have learning difficulties at school age.

Apgar Score↗

Prolonged inflammatory response to acute Pseudomonas challenge in interleukin-10 knockout mice.

Cystic fibrosis (CF) lung disease is characterized by a neutrophilic infiltrate that is excessive relative to the burden of infection. Decreased interleukin-10 in CF airways may impair proper termination of inflammation, leading to persistence of neutrophils after acute infections have been cleared. This could explain reports of lung inflammation in the absence of bacteria in infants with CF. We evaluated the kinetics of inflammation after transient Pseudomonas aeruginosa challenge in IL-10 knockout (KO) and wild-type (WT) mice. Both types of mice cleared the infection by Day 6 (p > or = 0.29). However, IL-10 KO mice had more neutrophils in bronchoalveolar lavage fluid than did WT mice on Days 4 (p < 0.0001), 6 (p < 0.0001), and 8 (p = 0.042). IL-10 KO mice had high concentrations of proinflammatory cytokines in BAL on Days 2 and 4, with some cytokines detectable on Days 6 and 8, whereas cytokines in BAL from WT mice were greatest on Day 2 and undetectable by Day 4. Moreover, IL-10 KO mice failed to regenerate IkappaBalpha once degraded and subsequently had prolonged activation of NF-kappaB. These data suggest that IL-10 deficiency contributes to prolonged inflammatory responses early in CF, when infection may be transient.

Acute Disease↗

Heart rate variability in healthy newborn infants.

In adults and older children, heart rate variability (HRV) is frequently used to study autonomic function noninvasively. Normal values of HRV in newborn infants, however, are not widely available. This problem may be partially attributed to the lack of standardization of different methods. This study assessed HRV in normal newborn infants using 24-hour Holter monitoring. From 1997 to 2000, we prospectively evaluated frequency- (spectral analysis), geometric-, and time-domain indexes of HRV in normal term infants. Ninety-six asymptomatic infants who were <72 hours old were studied. Frequency-domain parameters (power in the high, low, very low, ultra low, and total frequency domains), a geometric parameter (HRV triangular index), and time-domain parameters (SDNN, SDANN, SDNNi, r-MSSD, s-NN50) are reported as means +/- SD, medians, and 5th and 95th percentiles to establish the normative values for newborns. A high degree of correlation (r > or = 0.85, p <0.0001) was noted among the 3 vagal tone dependent parameters, such as high-frequency power (frequency domain), r-MSSD, and s-NN50 (time domain). Our study supports the use of vagal dependent time-domain parameters like r-MSSD and sNN50 as surrogates for high-frequency power in newborns. Because the data are reported as means +/- SD, medians, and 5th and 95th percentiles, their use facilitates the study of parasympathetic and sympathetic activity in comparable populations.

Electrocardiography, Ambulatory↗

Autonomic alterations in cocaine-exposed infants.

BACKGROUND: Heart rate variability (HRV) reflects autonomic control of the heart. After intrauterine cocaine exposure, asymptomatic newborn infants within 72 hours of life have decreased HRV. It is unknown whether these alterations are transient (acute effect) or persist in older infants and possibly reflect a teratogenic effect of cocaine. METHODS: This study prospectively evaluated HRV in 2- to 6-month-old infants who were exposed to cocaine in-utero (Group 1, n = 71). Their data were compared to normal controls (Group 3, n = 77) and to newborns exposed to drugs other than cocaine (Group 2, n = 89). Based on our previous study, heavy and light cocaine exposure was also defined a priori as the amount of cocaine used during the pregnancy that was more than or less than the 70th percentile, respectively. RESULTS: At the age of 2 to 6 months, infants with in-utero cocaine exposure had higher vagal tone and higher HRV (total power) than normal controls (no exposure to drugs). Most of this increase in vagal tone occurred in the light-cocaine-exposure group. HRV and vagal tone in the heavy-cocaine-exposure group were similar to the noncocaine-exposed group. CONCLUSIONS: At 2 to 6 months of age, asymptomatic infants exposed to cocaine in-utero have recovered from lower HRV seen within 72 hours of age. Infants exposed to light cocaine recovered by a rebound by increasing their vagal tone to above-normal levels. A similar response was blunted in heavily-cocaine-exposed infants. These alterations noted at follow up suggest a possible teratogenic effect of cocaine on the developing autonomic system.

Autonomic Nervous System↗

Quantification of regional left ventricular wall motion in newborns by color kinesis.

BACKGROUND: Normal values for regional left ventricular wall motion, although documented in adults, have not been reported in healthy newborns. METHODS: This study prospectively evaluated global and segmental systolic and diastolic cardiac function by color kinesis in clinically asymptomatic healthy newborns. RESULTS: Eighty-eight asymptomatic infants who were less than 48 hours old were studied. Systolic and diastolic parameters of global and regional left ventricular function are reported as means +/- SD, medians, 5th and 95th percentiles to establish the normative values for newborns. The reported fractional area changes during systole and diastole are similar to the reported normal values for older subjects. Higher body surface area significantly correlated with an increased peak velocity during systole, and fractional area changes during filling of the lateral wall. CONCLUSIONS: Our report of left ventricular regional wall-motion characteristics of healthy newborns, as evaluated by color kinesis, may help in the objective evaluation and management of newborns suspected to have global or segmental ventricular dysfunction.

Body Surface Area↗

Diastolic alterations in infants exposed to intrauterine cocaine: a follow-up study by color kinesis.

BACKGROUND: During the first 48 hours of life, newborn infants exposed to cocaine in utero have left ventricular diastolic segmental abnormalities. It is unknown whether these abnormalities are transient because of short-term effects or persist in older infants, possibly reflecting a teratogenic effect of cocaine. METHODS: This study prospectively evaluated global and segmental systolic and diastolic cardiac parameters by color kinesis. The patients were 2- to 6-month-old infants who were exposed to cocaine in utero (N = 56). Their data were compared with normal control patients with no intrauterine drug exposure (N = 60) and newborns exposed to drugs other than cocaine (N = 72). RESULTS: At the age of 2 to 6 months, there was no significant difference in the measured color kinesis parameters among the cocaine-exposed and the 2 control groups (infants prenatally exposed to other drugs and no drugs). Infants exposed to heavy cocaine prenatally, as compared with the noncocaine-exposed group, had a significant (P =.007) increase in septal fractional area change during left ventricular filling. CONCLUSIONS: At 2 to 6 months of age, infants have recovered from initial left ventricular diastolic segmental alterations seen in the first 48 hours of life except for the septal wall in the heavily cocaine-exposed group.

Cocaine↗