Interrelationships between obesity, obstructive sleep apnea syndrome and cardiovascular risk in obese adolescents.

BACKGROUND/OBJECTIVES: Obstructive sleep apnea syndrome (OSAS) may be a cardiovascular disease (CVD) risk factor independently of obesity in adults. Pediatric studies have associated OSAS with endothelial dysfunction, but few studies have examined relationships between OSAS and macrovascular sequelae. Our objective was to examine OSAS's independent contribution to macrovascular CVD risk measures in obese adolescents. SUBJECTS/METHODS: This cross-sectional observational study was conducted at Children's Hospital of Philadelphia Clinical Research and Academic Sleep Centers, and University of Pennsylvania Vascular Research Unit. Thirty-one obese non-diabetic adolescents underwent anthropometric measurements, overnight polysomnography, fasting laboratory draw and cardiovascular imaging. Cardiovascular outcome measures included maximal carotid intima-media thickness (cIMTmax), a measure of carotid structural changes, and carotid-femoral pulse wave velocity (CFPWV), an aortic stiffness measure whose relationship vis-à-vis OSAS in children has not been previously examined. Carotid diameter and augmentation index (AIx, measuring central pressure augmentation from wave reflections) were assessed. Potential confounding variables examined included blood pressure, lipoproteins, high-sensitivity C-reactive protein, insulin and glucose. RESULTS: The apnea hypopnea index, a primary OSAS measure, was not associated with cIMTmax, carotid diameter, CFPWV or AIx. body mass index (BMI) associated positively with cIMTmax (r=0.52, P=0.006) and CFPWV (r=0.45, P=0.01). Mean asleep end-tidal CO2 was negatively associated with carotid diameter (r=-0.63, P<0.0005). Insulin levels were negatively associated with AIx (r=-0.53, P=0.02). CONCLUSIONS: OSAS did not predict carotid structural changes or arterial stiffness independently of BMI in obese adolescents. Higher insulin levels associated with lower central pressure wave augmentation. Finally, long-term hypercapnia may predispose to carotid narrowing.

Predictive power of first morning glucose and the ketogenic diet.

The purpose of this study was to determine if hypoglycemia or hyperglycemia predicts the response to a ketogenic diet (KD) in a cohort of children with intractable epilepsy. We evaluated whether morning blood glucose during the initial 21 days after initiation of the KD in children with IE was related to seizure reduction after 3 months of treatment. The relation between change in weight status and blood glucose was also explored. Fasting morning whole blood glucose was measured each day for the first 21 days after initiation of KD. Weight and height were obtained at baseline, day of discharge, and at 0.5 and 1 month of full KD therapy. Associations among clinical response to the KD (responder status defined as >50% reduction of seizure frequency at 3 months), hypoglycemia, hyperglycemia, style of KD initiation protocol (fasting or gradual) and weight status were evaluated. Forty-five subjects age 1-12 years were enrolled. KD responder status was not associated with low or elevated blood glucose or type of initiation style protocol. Variability in day-to-day blood glucose also did not predict response to KD. Children who had declining weight status during KD initiation were more likely to be hypoglycemic during full KD therapy. Low blood glucose during KD therapy was not necessary for clinically significant seizure reduction. Hypoglycemia was related to declining weight status irrespective of initiation style protocol. An effective KD can be provided in a manner to minimize side-effects and maximize efficacy.

Addition of topical pimecrolimus to once-daily mid-potent steroid confers no short-term therapeutic benefit in the treatment of severe atopic dermatitis; a randomized controlled trial.

BACKGROUND: Combination therapy with pimecrolimus cream 1%, a topical calcineurin inhibitor (TCI), and fluticasone propionate cream 0.05% (FP), a mid-potency topical corticosteroid, may have a synergistic effect for treatment of atopic dermatitis (AD) because their mechanism of action differs. OBJECTIVES: To assess the efficacy of concomitant pimecrolimus twice daily/FP once daily vs. vehicle twice daily/FP once daily in patients with severe AD. METHODS: An exploratory, 2-week, double-blind, randomized, within-patient study was conducted (n = 45). Two target areas of similar severity, size and location were assessed. Assessments included the modified Eczema Area and Severity Index (0-12 scale) (primary variable), localized investigator global assessment (0-4 scale) and Patients' Self-Assessment of Disease Severity (0-4 scale). RESULTS: Data for all variables were similar for the TCI/FP and vehicle/FP treatments. CONCLUSIONS: The efficacy observed for treatment of severe AD flares with this TCI/FP combination regimen was equivalent to that of vehicle/FP.

Children with autistic spectrum disorders. I: comparison of placebo and single dose of human synthetic secretin.

AIMS: To examine the effect of a single dose of human synthetic secretin (HSS) on behaviour and communication in children with autism spectrum disorder (ASD) using an objective measure of communication and social reciprocity and standardised rating scales. METHODS: Randomised, crossover, double blind, and placebo controlled trial of a single intravenous dose of human synthetic secretin (HSS) 2 CU/kg. The 62 subjects (3-8 years) were assigned to group 1 (saline placebo/HSS) or group 2 (HSS/saline placebo). Diagnosis was confirmed by ADI-R (Autism Diagnostic Interview-Revised) algorithm. Severity of symptoms was rated using the CARS (Childhood Autism Rating Scale). Outcome measures included Communication and Symbolic Behavior Scale (CSBS), Ritvo Real-life Rating Scale, weekly Global Rating Scale (GBRS) by parents and teachers, and daily log of gastrointestinal symptoms. The communication subscale of the CSBS, specifying communication function, reciprocity, and social-affective signalling was videotaped and scored by a blinded, trained observer. RESULTS: Sixty one children completed the study. After randomisation, there were no significant differences in gender, race, age, and parent and teacher GBRS and Ritvo Scale between the two groups. Compared with placebo, secretin treatment was not associated with significant improvement of CSBS standard scores from baseline to 2 or 4 weeks post-infusion. Five children showed clinical improvement in standard scores: two after HSS and three after placebo. There were no significant changes in gastrointestinal symptoms after HSS or saline placebo. CONCLUSIONS: A single dose of intravenous human secretin is not effective in changing behaviour and communication in children with ASD when compared to placebo.

Children with autistic spectrum disorders. II: parents are unable to distinguish secretin from placebo under double-blind conditions.

BACKGROUND: Standardised measures of behaviour have failed to detect short term improvement in children with autism following treatment with secretin. However, it is possible that standardised measures are insensitive to dimensions of child behaviour that are nonetheless detectable by parents. AIM: To determine the ability of parents of children with autism to guess, under double blind conditions, whether their child had received secretin or placebo. METHODS: 2x2 crossover randomised blinded study, comparing the effect of synthetic human secretin 2 U/kg to placebo (saline). Sixty two children with autism (aged 43-103 months) were randomly allocated to two groups: group 1 received placebo, followed six weeks later by secretin, and group 2 received secretin followed by placebo. At the conclusion of the study, parents were asked to guess their child's group assignment. RESULTS: Twenty seven families guessed their child's group assignment correctly and 27 guessed incorrectly. In 48 instances, parents based their guess on perceived improvement; in six cases, parents based their guess on perceived deterioration. Six families saw no difference after either infusion, and offered no guess. One family dropped out after the first infusion, and one family was lost to follow up after the second infusion. CONCLUSION: In a controlled setting, parents of young children with autism are unable to distinguish the short term behavioural effects of secretin from placebo.

Who can give a pediatric trauma history for children injured in bicycle crashes?

Emergency Departments are important sites for injury surveillance but the quality of data collected has not been evaluated. This prospective cohort study assessed the ability of various respondents to provide circumstantial information following pediatric bicyclist trauma. A semi-structured survey tool was administered in the Emergency Department of a Level One Pediatric Trauma Center for 448 child bicyclists. The injured child provided more complete information when compared to witnesses and Emergency Medical Services personnel. No one respondent type provided the complete history. To obtain thorough injury circumstantial information, multiple respondents should be interviewed utilizing a semi-structured questionnaire.

Looking beyond the physical injury: posttraumatic stress disorder in children and parents after pediatric traffic injury.

BACKGROUND: Traffic crashes are the leading health threat to children in the United States, resulting in nearly 1 million injuries annually. The psychological consequences of these injuries are primarily unknown. The aims of this study were to estimate the prevalence of posttraumatic stress disorder (PTSD) in traffic-injured children and their parents and to identify risk factors for PTSD development. METHODS: A prospective cohort study of traffic-injured children between 3 and 18 years of age was conducted at a level 1 Pediatric Trauma Center. The children were enrolled as part of an ongoing surveillance system of traffic-related injuries. Presence and severity of PTSD were determined in the children and their parents through a validated diagnostic questionnaire 7 to 12 months after child injury. RESULTS: Twenty-five percent of the children and 15% of the parents suffered diagnostic PTSD, but only 46% of the parents of affected children sought help of any form (including from friends) for their child and only 20% of affected parents sought help for themselves. Child PTSD was associated with older child age and parent PTSD. Parent PTSD was associated with younger child age, child PTSD, and parent witnessing the event. Injury severity was not predictive of PTSD. CONCLUSIONS: PTSD in children and their parents is a common, yet overlooked, consequence of pediatric traffic-related injury with prevalence rates similar to those found in children exposed to violence. Physicians managing the pediatric trauma patient, regardless of injury severity or whether the injury was intentional, should screen for PTSD and refer for treatment where appropriate.

Hidden spears: handlebars as injury hazards to children.

OBJECTIVES: To delineate the mechanism of serious bicycle handlebar-related injuries in children and make recommendations for preventive strategies. METHODS: Prospective cross-sectional surveillance system of seriously injured child bicyclists supplemented by in-depth, on-site crash investigation to delineate specific injury mechanisms. Interdisciplinary analyses involved engineers, clinicians, epidemiologists, and biostatisticians. SETTING: The emergency department and in-patient trauma service of an urban level one pediatric trauma center between October 1995 and September 1997. PARTICIPANTS: Patients under 18 years of age who were treated for serious bicycle-related injuries (Abbreviated Injury Scale scores of 2 or greater). RESULTS: The surveillance system identified two distinct circumstances for serious child bicyclist injury: 1) handlebar-related injuries associated with minor incidents (falls from bicycles) and 2) nonhandlebar-related injuries associated with severe incidents (bicycle-motor vehicle crashes). Crash investigations explored the minor incidents that resulted in serious handlebar-associated injuries. In the typical mechanism, as the child lost control of the bicycle and began to fall, the front wheel rotated into a plane perpendicular to the child's body. The child then landed on the end of the handlebar resulting in serious truncal injuries. CONCLUSIONS: A discordancy exists between the apparently minor circumstances and serious injuries sustained by child bicyclists who impact bicycle handlebars. Recognition of the mechanism of handlebar-related injuries might aid the practitioner in early diagnosis of serious abdominal injuries in child bicyclists. This injury mechanism may be avoided through bicycle redesign that would involve both limiting rotation of the front wheel and modifying the ends of handlebars. An integrated approach involving a surveillance system to identify an injury hazard supplemented by in-depth, on-site crash investigations effectively provided the detailed mechanism of injury needed to develop interventions.

A comparison of awake versus paralyzed tracheal intubation for infants with pyloric stenosis.

UNLABELLED: This prospective, nonrandomized, observational study of 76 infants with pyloric stenosis was conducted at an academic children's hospital and compared awake versus paralyzed tracheal intubation in terms of successful first attempt rate, intubation time, heart rate (HR) and arterial hemoglobin oxygen saturation (SpO2) changes, and complications. Three groups were determined by intubation method: awake (A) with an oxygen-insufflating laryngoscope, after rapid-sequence induction (R), or after modified rapid-sequence induction (M) including ventilation through cricoid pressure. Successful first attempt intubation rate was 64% for Group A versus 87% for paralyzed Groups R and M (P = 0.028). Median intubation time was 63 s in Group A versus 34 s in Groups R and M (P = 0.004). Transient, mild decreases in mean HR and SpO2 and incidences of significant bradycardia and decreased SpO2 did not vary by group. Complications, including bronchial or esophageal intubation, emesis, and oropharyngeal trauma, were few. Senior anesthesiologists intervened in four tracheal intubations. We advocate anesthetized, paralyzed tracheal intubation because struggling with conscious infants takes longer, often requires multiple attempts, and prevents neither bradycardia nor decreased SpO2. After induction, additional mask ventilation with O2 confers no advantage over immediate tracheal intubation in preserving SpO2. IMPLICATIONS: In our children's hospital, awake tracheal intubation was not superior to anesthetized, paralyzed intubation in maintaining adequate oxygenation and heart rate or in reducing complications, and should be abandoned in favor of the latter technique for routine anesthetic management of otherwise healthy infants with pyloric stenosis.

Genetic and environmental influences on cardiovascular disease risk factors in adolescents.

BACKGROUND: Although there is consensus that prevention of cardiovascular diseases is a worthwhile activity and that these efforts should begin in childhood, some controversies remain about the efficacy and timing of preventive efforts. OBJECTIVE: To differentiate the cardiovascular risk factors that have a potential to respond to environmental and lifestyle modification. METHODS: The sample consisted of 56 monozygotic and 29 same-sex dyzogotic twin pairs, equally distributed by gender with a mean age of 12.62 years. Systolic and diastolic blood pressure, triceps skinfold thickness, body mass, and fasting blood specimens for lipid profiles were collected during home visits. Teachers rated the subjects' Type A behaviors using the Matthews Youth Test for Health. RESULTS: Statistically significant estimates of genetic variance were obtained for cholesterol, triglycerides, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, and body mass index. Compared with the previous phase of this longitudinal study, higher estimates of genetic variance were observed for components of the lipid profile and blood pressure and lower estimates were observed for Type A behavior variables. CONCLUSIONS: Overall, the genetic influence on risk factors was moderate, leading to the conclusion that the potential to modify risk profiles during the transition from childhood to adolescence is substantial. Attitudes, behaviors, and environmental inducements that establish and maintain healthy lifestyles over long period should be the focus of interventions and further research.

Immune responses in mothers of term and preterm very-low-birth-weight infants.

Differences in the levels of immune cell subsets present in peripheral blood have been demonstrated based on sociodemographic factors such as age and race. Postpartal women, who are recovering from the immune changes that are concomitant with pregnancy, have lymphocyte and monocyte values that differ from other populations. A subgroup of postpartal women, mothers who deliver preterm very-low-birth-weight (VLBW) (< or = 1,500 g) infants, may have further differences in values of immune cell subsets and in immune functioning either because of hormonal factors or lifestyle changes or because of the stress they experience after their infant's birth and for the first few months of infant caretaking. This study examined anxiety, depression, and immune cell phenotypes in 30 mothers of VLBW infants and in 30 mothers of healthy term infants over the first 4 postpartal months to determine if mothers of preterm VLBW infants differed from mothers of healthy term infants in psychological and immunologic parameters. Additionally, lymphocyte proliferation and natural killer cell functional assays were performed in a subset of mothers. Mothers of VLBW infants had increased anxiety and decreased lymphocyte proliferation compared to mothers of term infants. When lymphocyte and monocyte subsets were compared over time between the two groups of mothers differences were found in CD8, CD20, CD3-/CD56+, CD14, and HLA class II Ia on monocytes. Mothers with high-fat diets had lower percentages of some monocytes (CD14), lymphocytes (CD4+/CD45RA+), and natural killer cells (CD3-/CD57+) during the first 4 postpartal months.

Kinetics of retinyl esters during postprandial lipemia in man: a compartmental model.

Orally ingested vitamin A (retinol) is incorporated into intestinal chylomicrons (CHYLO) in the form of retinyl esters (RE) along with newly absorbed dietary triglycerides (TG). As the intestinal lipoproteins undergo hydrolysis in the circulation, the majority of the RE remain with the secreted intestinal particles and have been used as a marker for intestinally derived lipoproteins during the early phase of the postprandial state. A multicompartmental model was developed for the kinetics of RE during postprandial lipemia in individuals with normal lipid levels (n = 16) and in patients with hyperlipidemia (n = 44). The assumptions used in the development of the model are presented in this report. Some of the key findings include (1) as much as 50% of the newly synthesized RE may be secreted by the intestine as very-low-density lipoprotein (VLDL)-sized particles of S(f) 20 to 400 following consumption of a test meal containing a moderate amount of fat (20 to 30 g); (2) in most individuals, approximately 50% of the RE secreted in S(f) greater than 400 are converted to smaller, less buoyant fractions, and 50% are irreversibly removed directly from the plasma; (3) as much as 5% to 20% of the ingested retinol may be secreted as small intestinal lipoproteins with the buoyance of low-density lipoprotein (LDL) in some individuals; and (4) less than 5% of RE flux through S(f) 20 to 400 is converted to S(f) less than 20, and the primary catabolic pathway for RE in this fraction is direct uptake. Comparable estimates can be obtained for the kinetic parameters when repeat studies are made in the same subjects under comparable conditions.

Recognition of tubo-ovarian abscess in adolescents with pelvic inflammatory disease.

PURPOSE: Ultrasonography of the pelvis is commonly used to diagnose tubo-ovarian abscess (TOA) in patients with pelvic inflammatory disease (PID). Our objective was to determine whether the clinical features of PID differ in adolescents with and without TOA. METHODS: A retrospective design was used to derive and validate a clinical model differentiating adolescents with PID who did and did not have TOA. The study population consisted of hospitalized adolescents with a discharge diagnosis of PID. Of the 208 patients discharged from January 1, 1990, to July 31, 1993, 87 (42%) met published criteria for PID and comprised the derivation set. Of the 63 patients from August 1, 1993, to June 24, 1994, 30 (48%) met criteria and comprised the validation set. All patients had pelvic ultrasonography performed during hospitalization. The ultrasonography records were reviewed retrospectively for TOA, ovarian and uterine size, clarity of tissue planes, and endometrial or cul-de-sac fluid. Medical records were reviewed for sociodemographic characteristics, medical and sexual history, physical examination, laboratory results, and hospital course. RESULTS: TOA was present in 17% of the derivation set and 20% of the validation set. A six-variable model developed on the derivation set performed best in differentiating the TOA and non-TOA groups: last menstrual period > 18 days prior to admission (60% and 17%), previous PID (53% and 22%), palpable adnexal mass (13% and 3%), white blood cell count > or = 10,500/microliters (33% and 64%), erythrocyte sedimentation rate > 15 mm/h (33% and 64%), and heart rate > 90/min (40% and 78%). In the derivation and validation sets, the model correctly identified 78 and 83% of the TOA groups and 88 and 77% of the non-TOA groups. The area under the receiver operating characteristic curve of the model was 0.92 in the derivation set and 0.87 in the validation set. CONCLUSIONS: We conclude that clinical characteristics help identify adolescents with acute PID who have TOA. These patients may have fewer signs of acute illness than those without TOA and may develop symptoms later in the menstrual cycle.

The influence of age and relative weight on the presentation of familial combined hyperlipidemia in childhood.

BACKGROUND: Familial combined hyperlipidemia (FCHL) has been described as the leading cause of familial hyperlipidemia. FCHL is dominantly inherited, occurs in at least 1% of the population, and is responsible for about 10% of premature coronary artery disease (CAD). OBJECTIVE: Because FCHL in childhood is not well characterized, we evaluated the interrelationships among age, percentage of ideal body weight (%IBW) and plasma lipoprotein levels in FCHL children (age 2-18 years), exploring the possibility that obesity and age may influence the presentation of FCHL in childhood. METHODS: One hundred and eighty-nine children with FCHL were studied. Significant correlations within this group were further evaluated by examining a subset of 36 FCHL children, each of whom had an unaffected sibling who could serve as a control for comparison. RESULTS: When the full group was divided into those with TG levels > 90% and those with TG levels < 90%, the correlation with %IBW was stronger in the former (r = 0.45, P < 0.005) as compared with the latter (r = 0.25, P = 0.05). Within the subset of 36 FCHL children and their 36 unaffected siblings (controls), age and sex distributions were similar. Percentage IBW (mean +/- S.D.) (117.3 +/- 29.1 for FCHL and 111.2 +/- 19.4 for controls) was similar and in the overweight range. FCHL children had significantly higher levels of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (apo B) and triglyceride (TG) levels compared with controls (P < 0.0005 for all comparisons). Of several significant correlations observed in the full group (n = 189), only the correlations of %IBW with plasma TG levels (r = 0.45, P = 0.006), and of age with plasma TG levels (r = 0.48, P = 0.003) persisted with a similar degree of magnitude in the subset of 36 FCHL children. No correlation was significant in the controls. By Fisher's Z-test, the correlation between %IBW and TG in the FCHL children was significantly different from controls. CONCLUSIONS: These results suggest that TG levels in FCHL children, but not in their unaffected siblings, and sensitive to the presence of obesity, implying an interaction between obesity and the underlying condition, in addition, the association between age and TG level in FCHL children suggests a gradual expression of the hyperlipidermia (i.e. TG) during childhood.

A placebo-controlled trial using intravenous atropine as an adjunct to conscious sedation in pediatric esophagogastroduodenoscopy.

BACKGROUND: The usefulness of intravenous atropine as an adjunct to conscious sedation in pediatric esophagogastroduodenoscopy remains an unresolved issue. METHODS: This prospective, double-blind, randomized study examined 101 patients, who were randomized to receive either intravenous atropine 0.02 mg/kg (maximum 0.4 mg) or a placebo of normal saline solution prior to the procedure. RESULTS: The mean maximum heart rate during the procedure and the percentage of time that the heart rate was more than 1 standard deviation above mean for age was significantly greater in the atropine group as compared to the placebo group (p < 0.0005). There was no significant difference between groups in the amount of secretions noted, gastric motility, retching or vomiting, facial flushing, or dysphoria. There were no causes of significant bradycardia or hypotension in either group. There was a significant number of patients greater than 5 years of age and receiving meperidine and atropine (as compared with meperidine and placebo) whose arterial oxygen saturation dropped below 90% during the procedure (p = 0.0485). CONCLUSIONS: We found that the use of atropine when used as an adjunct to conscious sedation in children undergoing upper endoscopy did not increase the safety of the procedure or provide significant benefits. We do not recommend the routine use of atropine for upper endoscopy in pediatric patients.

Nongenetic influences of obesity on risk factors for cardiovascular disease during two phases of development.

Matched-pair analyses of twins were used to examine nongenetic influences of obesity on the lipid profile and systolic and diastolic blood pressure (cross-sectionally) during two phases of development--the school-age years (n = 73 twin pairs) and adolescence (n = 56 twin pairs)--and (longitudinally) in the transition between these two developmental phases. Data were collected during an early morning home visit. Results of the matched-pair t tests indicated significant environmental influences on obesity in both phases and in the transition (change in obesity) between these two phases. Intraindividual associations of obesity (kg/m3) and atherogenic lipids (total and LDL cholesterol) emerged during the school-age years. In adolescence, obesity was associated with HDL cholesterol and total triglyceride. Change in obesity (kg/m3) from the school-age years to adolescence was associated with total triglyceride. Results suggest an emphasis on obesity as part of CVD risk factor management in children and point to the importance of primary prevention early in life.

Obesity, school performance and behaviour of black, urban elementary school children.

Nutritional status, school performance and behaviour were assessed in a group of black, inner-city school children. Thirty-five per cent of the children were obese by triceps skinfold thickness criteria. The primary care taker's responses to the Child Behavior Checklist (CBCL) and the hyperactivity subscale of the Conners' Parent's Questionnaire indicated that the obese children were more likely to have abnormal scores. On the CBCL subscale scores, obese girls had a significantly higher 'sex problems' score. Although the other subscale scores were not significantly different, there was a significant trend for obese boys and girls to score higher on the CBCL subscale scores. In addition, the proportion of obese children placed in special education or remedial class settings was twice that for non-obese children. These results add to the limited information available concerning obese black children, and are consistent with previous findings suggesting subtle behaviour differences in obese children.

Use of cholestyramine in the treatment of children with familial combined hyperlipidemia.

We studied the effectiveness of and compliance with the use of cholestyramine in children with heterozygous familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL). During a 10-year period, 673 children (aged 10.5 +/- 4.0 years) were referred for evaluation of hyperlipidemia, of whom 87 (36 with FH; 51 with FCHL) were treated with cholestyramine (8 to 24 gm/day). In both groups, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B levels were significantly reduced after cholestyramine use. In those with FH, plasma LDL-cholesterol levels decreased from 258 +/- 35 mg/dl (6.67 +/- 0.90 mmol/L) to 190 +/- 31 mg/dl (4.91 +/- 0.80 mmol/L); in those with FCHL, LDL-cholesterol levels dropped from 207 +/- 40 mg/dl (5.35 +/- 1.03 mmol/L) to 141 +/- 35 mg/dl (3.64 +/- 0.90 mmol/L). High-density lipoprotein-cholesterol levels were not significantly changed after cholestyramine use in either group. In the FCHL group, plasma triglyceride levels increased significantly from 81 +/- 35 mg/dl (0.92 +/- 0.40 mmol/L) to 134 +/- 42 mg/dl (1.52 +/- 0.48 mmol/L). Seven patients were lost to follow-up; 18 discontinued the medication within 1 month. Of the remaining 62 children, 59 had a good response to the drug. Of the 62 patients, 52 discontinued the medication after 21.9 +/- 10 months. Adverse effects included foul taste (73%), nausea with bloating (18%), and constipation. Cholestyramine is effective in reducing LDL-cholesterol levels in children with inherited hyperlipidemia, but the majority of children will not comply with its long-term use.

Genotype at a major locus with large effects on apolipoprotein B levels predicts familial combined hyperlipidemia.

A sample enriched for familial combined hyperlipidemia (FCHL) was examined for evidence of an association between genotype at an apolipoprotein B (apoB) elevating locus defined by complex segregation analysis and FCHL. Complex segregation analysis detected a locus with a large effect on plasma apoB levels and was used to compute the most probable genotype of family members. None of the 35 normolipidemic adults carried a copy of the allele associated with elevated apoB levels, yet 58% of the 109 adults with FCHL carried 1 (29%) or 2 (28%) copies. Two of 28 (7%) normal children had 1 copy of this allele and none had 2 copies, while 88 of 182 (48%) children with FCHL had 1 (26%) or 2 (22%) copies. Further, 41 of 48 (85%) individuals classified as having hyperapobetalipoproteinemia did not carry a copy of this "elevated apoB" allele. Therefore, the presence of the allele associated with elevation of apoB level is highly predictive of FCHL and this association cannot be explained solely by the presence of elevated apoB levels in FCHL, suggesting that the locus controlling apoB levels may play an etiologic role in FCHL.

Prevalence and expression of familial combined hyperlipidemia in childhood.

The objectives of this study were (1) to determine the incidence of dominantly inherited hyperlipoproteinemia in children referred to our medical center because of hyperlipidemia associated with a family history of premature coronary artery disease and (2) to assess the degree of expression in childhood of the most common inherited hyperlipoproteinemia, familial combined hyperlipidemia. Among 129 families referred to us by area pediatricians, we identified a dominantly inherited hyperlipoproteinemia in 97 of them. Twenty had familial hypercholesterolemia, 65 familial combined hyperlipidemia, 11 hyperapobetalipoproteinemia, and one familial hypertriglyceridemia. As expected, almost half (9/20) of the siblings of probands with familial hypercholesterolemia were affected. Although we expected incomplete gene penetrance in the siblings of the probands with familial combined hyperlipidemia, we found 43 affected and 40 unaffected among the 83 siblings of the 65 probands. Our findings suggest that hyperlipidemia in children, caused by familial combined hyperlipidemia, occurs more than three times as frequently as familial hypercholesterolemia and that in families identified by a child proband, the penetrance is complete. Pediatricians should identify this primary hyperlipidemia in childhood and attempt to prevent the associated risk of premature coronary artery disease by prescribing appropriate diet and life-style modifications.