Triglyceride concentrations: the disaccharide effect.

The mean 24-hour or integrated concentration of triglyceride is significantly higher when dietary sucrose is provided rather than an equivalent amount of its component monosaccharides, glucose and fructose. In contrast, the plasma triglyceride concentration after a 12-hour fast is not significantly different.

Serum thyrotropin responses to synthetic thyrotropin-releasing hormone in normal children and hypopituitary patients. A new test to distinguish primary releasing hormone deficiency from primary pituitary hormone deficiency.

Synthetic thyrotropin-releasing hormone (TRH) was administered intravenously in a dose of 7 mug/kg to 20 normal children ages 4-13 yr. Serum thyroid-stimulating hormone (TSH) was measured by radioimmunoassay and rose from a mean value of 1.7 muU/ml (range = < 1.25-7.2) to a mean peak value of 21.5 muU/ml (5.2-33.2) at 15 or 30 min after administration.13 patients with idiopathic hypopituitarism and apparent normal thyroid function, ages 3-19 yr, responded to TRH in a manner very similar to the control subjects: TSH rose from a mean value of 1.8 muU/ml (range < 1.25-4.3) to a mean peak value of 18.5 muU/ml (range = 9.5-45.0) which occurred between 15 and 60 min after TRH.13 idiopathic hypopituitary patients with documented thyroid deficiency were tested after thyroid therapy had been discontinued for a minimum of 10 days. The serum TSH values in 10 of 13 patients rose from a mean base line level of 2.2 muU/ml (< 1.25-5.3) to a peak mean value of 32.5 muU/ml (9.6-61.3) between 30 and 120 min after TRH. In three patients, however, little or no TSH response was detected, even when serum thyroxine levels were extremely low. Similar to the latter group, three of five patients with hypopituitarism secondary to craniopharyngiomas had undetectable or barely measurable TSH levels before and after TRH. Two of these five patients had significant responses which were compatible with hypopituitarism resulting from damage to the hypothalamus or hypothalamic vessels instead of the pituitary. Side effects were experienced in 41 of 54 patients (76%). The effects were limited to a mild nausea-like sensation in 63% of the patients and occurred within the first 5 min after receiving TRH. No evidence of serious toxicity or long-term side effects was noted. The TRH test is a safe, effective way to measure TSH reserve in children. The positive response in 10 of 13 patients with secondary hypothyroidism supports data previously accumulated that most patients with idiopathic hypopituitarism have an abnormality of their hypothalamic-releasing hormone function, whereas the remaining minority probably have primary pituitary disease.

Integrated concentration of growth hormone in juvenile-onset diabetes.

Twenty-four-hour patterns of plasma growth hormone concentrations were evaluated during 50 studies of 42 subjects with juvenile-onset diabetes mellitus. Blood was sampled continuously over 24 h using a portable peristaltic pump under conditions in which subjects remained ambulatory and maintained their daily dietary and insulin regimens. All diabetics showed diurnal patterns characterized by frequent episodes of secretion of growth hormone. The mean 24-h concentration of growth hormone, designated the integrated concentration, was significantly higher among juvenile-onset diabetics (P less than 0.001) than it was in age- and sex-matched nondiabetic populations. Juvenile-onset diabetics younger than 20 yr had significantly higher (P less than 0.005) growth hormone integrated concentrations than did older juvenile-onset diabetics. There was no statistically significant correlation between the integrated concentrations of glucose and growth hormone; thus, the study failed to provide us with support for the hypothesis that elevated growth hormone concentrations in diabetics are a consequence of hyperglycemia. Variability of diurnal glucose concentrations was positively correlated (P less than 0.015) with the growth hormone integrated concentration among juvenile-onset diabetics. Our observations indicate that rapid declines in plasma glucose concentration or episodes of absolute hypoglycemia were significant factors, contributing to both the elevated integrated concentration and the secretory spiking of growth hormone observed in the diabetic population.

Hyperthyroidism caused by inappropriate thyrotropin hypersecretion: studies in patients with selective pituitary resistance to thyroid hormone.

We have identified the condition of thyrotropin (thyroid-stimulating hormone [TSH])-induced hyperthyroidism secondary to selective pituitary insensitivity to thyroid hormone in three patients. Each patient was clinically hyperthyroid, with elevated serum levels of thyroxine (T4) and triiodothyronine (T3) and detectable levels of serum TSH before therapy. After therapy each patient had notably elevated TSH levels at a time that peripheral levels of thyroid hormones were in the hyperthyroid range. Before and after therapy, serum levels of TSH were suppressed by therapy with liothyronine sodium and were stimulated by protirelin (thyrotropin-releasing hormone) both before and after liothyronine and dexamethasone treatment. Dexamethasone therapy decreased the levels of TSH, protirelin-stimulated TSH, and circulating T4 and T3. Serum levels of glycoprotein alpha-subunit were 0.6 to 2.4 ng/ml, values considerably lower than found in patients with TSH-secreting pituitary tumors. We suggest that the frequency of TSH-induced hyperthyroidism secondary to pituitary insensitivity to thyroid hormone may be higher than presently indicated in the medical literature.

Validity of urine glucose measurements for estimating plasma glucose concentration.

Both physicians and diabetic patients have traditionally relied on measurement of glycosuria as an indirect method of estimating plasma glucose concentration to guide adjustment of insulin and diet therapy. Our observations on the correlation between mean plasma glucose concentration with simultaneous urine glucose concentration or excretion rate re-emphasize the limitations of this approach. Although our observations show a significant correlation (P less than 0.0001) between plasma glucose concentration and urine glucose concentration or urine glucose excretion rate, the wide confidence limits [95% confidence limits (minimum) +/- 150 mg/dl] on plasma glucose concentration estimated from urine glucose measurements limit the clinical applicability of such estimates. Differences among subjects in the renal resorption of glucose contribute to the wide variance of estimates. However, significant variability in renal glucose resorption within individuals is documented, further reinforcing the limitations of urine glucose determinations for reliable estimates of plasma glucose concentrations. Diabetologists need to reconsider the applicability of urine glucose measurements in evaluation of adequacy of therapy and in adjustment of insulin dosage.

A survey of cognitive functioning at difference glucose levels in diabetic persons.

Cognitive functioning was assessed in diabetic patients during hypoglycemia (60 mg/dl), euglycemia/control (110 mg/dl), and hyperglycemia (300 mg/dl). Blood glucose levels were set and maintained to within 4% of targeted levels by an artificial insulin/glucose infusion system (Biostator). Attention and fine motor skills, assessed by visual reaction time, was slowed at altered glucose levels. Performance was less impaired during hyperglycemia than hypoglycemia when a longer interstimulus interval was used, although it was still slower than normal. The time required to solve simple addition problems was increased during hypoglycemia, although reading comprehension was not affected. The possibility that some automatic brain skills are disrupted at altered glucose concentrations is discussed, while associative or inferential skills may be less affected.

Triglyceride integrated concentrations: effect of variation of source and amount of dietary carbohydrate.

The effect of changes in the amount of dietary carbohydrate (45 or 65% of total energy) and in the source of carbohydrate (sucrose or corn syrup) on plasma triglyceride and cholesterol concentrations was studied in eight healthy males. Subjects ingested each of the four formula diets for 10 days in a latin square sequence. Diet-induced response was assessed by measurement of plasma lipid concentrations in blood obtained after overnight fast and by measurement of the mean plasma lipid concentrations--designated the integrated concentration--of blood obtained by 24 hr continuous blood withdrawal. The fasting plasma triglyceride concentration increased significantly during ingestion of the high carbohydrate diet (P less than 0.005) but was not significantly influenced by the source of carbohydrate calories. The 45% carbohydrate diets induced larger meal associated plasma triglyceride variation than 65% diets. Sucrose-containing diets induced significantly higher plasma triglyceride integrated concentrations than corn syrup diets, whether provided as 45% (P less than 0.05) or 65% (P less than 0.005) of total energy. Diet-induced changes in fasting or integrated plasma cholesterol concentration were minimal.

Methylphenidate treatment of hyperactive children: effects on the hypothalamic-pituitary-somatomedin axis.

To further define the influence of methylphenidate on the growth hormone-somatomedin axis and prolactin secretion, serum growth hormone and prolactin concentrations were assessed over 24 hours and in response to provocative stimuli. The nine hyperactive subjects were all studied during methylphenidate therapy and after drug discontinuation, Diurnal patterns of growth hormone and prolactin concentrations were assessed using an ambulatory, continuous blood withdrawal procedure to ensure that activity, caloric intake, and sleep patterns mimicked normal schedules. No significant difference in integrated concentration of growth hormone, fasting somatomedin concentration, or prolactin integrated concentration was detected between subjects receiving or not receiving methylphenidate. There was a significant increase in peak growth hormone response to arginine stimulation among subjects receiving methylphenidate therapy; however, this appeared to correlate with acute methylphenidate administration. These data do not support the hypothesis that growth defects in hyperactive children treated with methylphenidate are caused by alteration in the hypothalamic-pituitary-somatomedin axis.

Behavioral and emotional problems among preschool children in pediatric primary care: prevalence and pediatricians' recognition. Pediatric Practice Research Group.

This study examined how well private-practice pediatricians can identify emotional/behavioral problems among preschool children. Children aged 2 through 5 (N = 3876) were screened during a visit to 1 of 68 pediatricians who rendered an opinion about the presence of emotional/behavioral problems. Subsequently, children who scored above the 90th percentile for behavioral problems on the Child Behavior Checklist, along with children matched on age, sex, and race who had screened low, were invited for an intensive second-stage evaluation. There were 495 mothers and children who participated in that evaluation, which included a behavioral questionnaire, maternal interview, play observation, and developmental testing. Two PhD-level clinical child psychologists rendered independent opinions about the presence of an emotional/behavioral disorder. The psychologists identified significantly higher rates of problems overall--13.0% when the criterion was independent agreement that the child had an emotional/behavioral problem and a regular psychiatric diagnosis was assigned, vs 8.7% based on pediatricians' ratings. Prevalence rates based on psychologists' independent ratings were significantly higher than pediatricians' for both sexes, 4- through 5-year-olds, and whites, but not for 2- through 3-year-olds, African-Americans, and all minorities. Prevalence rates based on psychologists' ratings were significantly higher than the pediatricians' for all subgroups when V-code diagnoses were included in the psychologists' ratings. Overall, pediatricians' sensitivity was 20.5%, and specificity was 92.7%. At least 51.7% of the children who had an emotional/behavioral problem based on the psychologist's independent agreement had not received counseling, medication, or a mental health referral from the pediatrician.(ABSTRACT TRUNCATED AT 250 WORDS)

Free and total insulin integrated concentrations in insulin dependent diabetes.

Studies of the 24 hr insulin concentration profiles in diabetic subjects on chronic exogenous insulin have been hampered by the presence of endogenous anti-insulin antibody, which gives spurious estimates of radioimmunoassayable insulin concentrations. The introduction of polyethylene glycol precipitation of endogenous antibody has allowed development of reliable assays for determination of free and total insulin concentration in subjects on insulin therapy. This article reports our observations of plasma free and total insulin concentration in 50 Type I and Type II ambulatory insulin dependent diabetics, utilizing a continuous 24 hr blood withdrawal technique. In response to exogenous insulin, study subjects had marked elevations in insulin concentrations compared to controls. Mean free insulin integrated concentration was 3.5-fold higher in diabetics than nondiabetics. Mean total insulin integrated concentration was 868 microunits/ml, more than 20 times in excess of total insulin concentration in nondiabetics. There was a wide range among diabetics in the percentage of total insulin in the free insulin fraction. Neither free nor total insulin integrated concentration correlated with dose of exogenous insulin. Free and total insulin concentration profiles showed a limited range of variation in insulin concentration during the 24 hr of study, no subject having a profile that mimicked that observed in nondiabetic subjects. Glucose integrated concentration showed no correlation with free insulin integrated concentration, however, it did correlate inversely with the percentage of total insulin in the free insulin fraction. These data emphasize the difficulty in establishing normal patterns of insulin among diabetic subjects on conventional subcutaneous insulin therapy.

Psychopathology and health care use among preschool children: a retrospective analysis.

OBJECTIVE: To examine the relationship between psychopathology and health care utilization beginning in the preschool (ages 2 to 5) years. METHOD: Five hundred ten preschool children were enrolled through 68 primary care physicians. The test battery used for diagnoses included the Child Behavior Checklist, a developmental evaluation, the Rochester Adaptive Behavior Inventory, and a videotaped play session. Consensus DSM-III-R diagnoses were assigned using best-estimate procedures. Frequency of primary care visits was established through 1-year retrospective record review; mothers estimated total visits and emergency department (ED) use. RESULTS: Logistic regression models showed that a DSM-III-R diagnosis was related to increased ED use but not primary care or total visits. Greater functional impairment was associated with fewer primary care visits and more ED visits. Total, internalizing, and externalizing behavior problem scores were associated with increased primary care and total visits; ED visits were associated with increased total and internalizing problems. Child's health status consistently correlated with utilization. CONCLUSION: There is a consistent relationship between health care use and child psychopathology beginning in the preschool years.

Evaluation of a psychological treatment package for treating pain in juvenile rheumatoid arthritis.

We examined the utility of psychological treatment procedures for children with high levels of pain associated with juvenile rheumatoid arthritis (JRA). By the use of a multiple baseline across subjects design, four children were assigned to an immediate treatment group, and four children to a delayed treatment group. The six-session treatment included relaxation training, electromyogram, and thermal biofeedback for the child; mothers were trained in the use of behavioral techniques for managing physical therapy and school attendance. Visual inspection of the data indicates small changes on children's self-reported pain diary scores for mean pain and ratings of high (greater than 5 on a 10-point visual analogue scale) pain periods, with 50% to 62% showing at least a 25% reduction in pain immediately after treatment, and 62% to 88% showing a 25% reduction by 6-month follow-up. Maternal reports of changes paralleled those of the children. Comparisons of Mann-Whitney U-tests conducted pre- and posttreatment indicated no differences for children's ratings of mean pain or +5 pain ratings between the immediate and delayed treatment groups; greater improvement for the immediate treatment group was noted on maternal reports of both mean pain (p < 0.05) and +5 pain (p < 0.5) ratings. The reduction of pain reports from pretreatment to follow-up was significant for children's mean pain (p = 0.02), +5 pain ratings (p = 0.02), and mother's reports of mean pain (p = 0.03) and +5 pain periods (p = 0.01). Maternal reports of the number of pain-related behaviors that the child exhibited also declined (p < 0.05). No reduction in physical therapist's ratings of pain during evaluation were noted. No increases in maternal reports of child's psychological adjustment problems were reported following treatment. Results provide modest support for the use of psychological interventions with patients with JRA.

Interrater reliability of the DSM-III-R with preschool children.

Little attention has been paid to evaluating the use of DSM-III-R with preschool children. Children (N = 510) ages 2 to 5 years who were screened at the time of a pediatric visit were selected to participate in an evaluation which included questionnaires, a semistructured interview, developmental testing, and a play observation. Following the evaluation, two clinical child psychologists independently assigned DSM-III-R diagnoses. For each diagnostic category, kappa and Y coefficients were calculated; Y coefficients are less sensitive to base rates of disorders. For overall agreement, the weighted mean kappa (.61), and mean Y (.66) were moderately high. Overall agreement that the child had at least one of the disruptive disorders was substantial (kappa = .64; Y = .65); agreement that there was at least one of the emotional disorders was moderate for kappa (.54), but substantial for Y (.70). Kappa coefficients were higher for major categories of disorder than for specific disorders; however, Y coefficients did not show a decline for specific disorders. Interrater reliability of DSM-III-R appears to be similar for preschoolers and older children.

Cardiac function in primary hypothyroidism.

Cardiac chamber dimensions and myocardial function were studied in 15 children with primary hypothyroidism prior to and after thyroxine therapy. Small pericardial effusions were detected in 11 of 15 subjects before therapy, which resolved in nine of 11 subjects after initiation of thyroxine replacement. There was no association between the severity of the thyroid failure and the presence of effusion, and no evidence of cardiac compromise due to effusions. No significant abnormality in cardiac chamber or myocardial dimensions, systolic time intervals, or indices of myocardial contractility was detected among the hypothyroid children as compared with a normal population. Neither myocardial dimensions nor contractility indices changed significantly on reestablishment of normal thyroxine concentrations with exogenous hormone. These data refute the existence of a myocardiopathy associated with hypothyroidism in children.

Factors related to grade retention in children with short stature.

A recent study by Holmes et al. (1982) revealed a high degree (23%) of grade retention in a group of children with significant short stature secondary to growth hormone deficiency (GHD), constitutional delay (CD); or Turner's Syndrome (TS). Parents indicated in a free response format that 'immaturity' and 'small size' were the reasons for retention. The present follow-up study obtained academic achievement data on 47 of the 56 short children from the Holmes et al. (1982) study to assess what role academic factors, not spontaneously mentioned by parents, may have had in the retention decision. Results indicated that despite repeating a year in the primary grades, the group of retained children were still functioning 6 months below grade expectation, compared to grade appropriate achievement in the never-retained group. Parents and teachers were both accurate in their perceptions of children's academic achievement. Behavioural ratings by teachers indicated more adjustment difficulties for retained children, while parent ratings of behaviour showed a similar high level of problems for short children regardless of retention status. Although both groups of children possessed average intellectual abilities, the retained children obtained lower IQ scores than the never retained children. In summary, a majority of short children were achieving appropriate grade levels, but a substantial minority were experiencing under-achievement, behaviour problems, and grade retention, despite average intelligence.

Immunogenetic studies in families of children with juvenile dermatomyositis.

OBJECTIVE: We reported an association between juvenile dermatomyositis (JDMS) and the HLA-DQA1*0501 allele. The purpose of this study was to determine whether there is evidence for linkage between JDMS and the DQA1*0501 allele in JDMS families. METHODS: The study population included 18 unrelated patients with JDMS, their parents, and 49 unaffected siblings. Using molecular genetic techniques, we studied the HLA genes, DRB1, DQA1, and tumor necrosis factor-alpha. RESULTS: Using the transmission disequilibrium test, we confirmed our earlier observations that the HLA-DQA1*0501 allele confers primary susceptibility to JDMS. CONCLUSION: DQA1*0501 confers genetic risk for JDMS; we cannot exclude the effects of alleles at other linked loci that were not studied or interactive effects between DQA1 alleles and alleles at other loci.

Psychological factors affecting reported pain in juvenile rheumatoid arthritis.

Examined the extent to which psychological variables are correlated with pain reported by children with juvenile rheumatoid arthritis (JRA). In a hierarchical multiple regression analysis with pain as the dependent variable, four psychological measures of child and family functioning resulted in a significant increase in R2 = .31, p < .0001, after the effects of disease characteristics were considered. Greater emotional distress in the child, greater emotional distress of the mother, and greater family harmony were related to higher reported pain. Findings suggest that more attention should be given to nonpharmacological aspects of pain and pain management in children with JRA.

Conceptions of illness by children with juvenile rheumatoid arthritis: a cognitive developmental approach.

Investigated the conceptions of illness and accuracy of understanding about their disease for children with juvenile rheumatoid arthritis (JRA). 54 children between the ages of 6 and 17 were interviewed individually about various aspects of JRA, with results suggesting that accuracy and illness conceptions could be reliably measured. As predicted, children's understanding about their disease followed a developmental progression, with older children demonstrating a more sophisticated understanding of JRA than younger children (significant differences between age groups on 3 of the 5 questions). Multiple regression analysis indicated that conceptual level (p < .001) was a better predictor of the child's accuracy of knowledge than was age (ns). Despite the developmental progression, there were a significant number of children functioning below the level expected for their age. In fact, the majority (75%) of children exhibited an understanding of JRA at the concrete operational level of cognitive development. The within-subject variability and striking misconceptions argue for ongoing evaluation of each child's understanding as a way to improve educational efforts.