Risk factors for cardiovascular disease in children with Type I diabetes.

BACKGROUND: The major cause of morbidity and mortality in individuals with Type I insulin-dependent diabetes mellitus (IDDM) is premature and extensive atherosclerotic cardiovascular disease (CVD). OBJECTIVES: To determine the prevalence and predictors of hypercholesterolemia and to examine the distribution and interrelationship of risk factors for CVD. METHODS: This observational (mixed-longitudinal) study, guided by an epidemiologic framework, assessed a sample of 140 children with IDDM. Total cholesterol (TC) and diabetes control were measured in the total sample. Standard CVD risk factors were measured in a subsample of 67 children. RESULTS: Observed frequency of TC greater than the 75th percentile and greater than the 95th percentile was significantly more than expected (p < 0.01 and p < 0.0001, respectively). In the total sample, TC-CVD risk factor associations were not observed. However, diabetes control and physical activity were correlated with TC in the risk sample of children at highest risk, as demonstrated by hypercholesterolemia. CONCLUSIONS: Results demonstrate the importance of assessing the lipid profile in children with IDDM and monitoring CVD risk factors in hyperlipidemic children with IDDM. Future research should focus on prospective longitudinal studies in population-based multiethnic samples of children with IDDM.

Comparison of urine dipstick, microscopy, and culture for the detection of bacteriuria in children.

The authors compared dipstick tests for leukocyte esterase and nitrite and microscopic examination of urinary sediment with urine culture to assess whether the former tests could reliably rule out bacteriuria in specimens from children. The authors studied urine specimens from 1010 infants and children younger than age 18. Compared with culture at greater than or equal to 10(5) colony forming units (cfu)/ml, the sensitivities of leukocyte esterase, nitrite, and microscopic examination of white blood cells (greater than or equal to 5 wbc/hpf) or bacteria (in at least moderate numbers) were 76 percent, 29 percent, 82 percent, and 80 percent, respectively. The specificities of the same tests were 81 percent, 99 percent, 81 percent, and 83 percent, respectively. Compared with culture at greater than or equal to 10(4) cfu/ml, the sensitivities of the tests were 64 percent, 21 percent, 64 percent, and 59 percent; the specificities were 82 percent, 99 percent, 81 percent, and 83 percent, respectively. The negative predictive values of leukocyte esterase and microscopic examinations of urinary sediment for white blood cells and bacteria were all 95 percent (greater than or equal to 10(4) cfu/ml) or 98 percent (greater than or equal to 10(5) cfu/ml). The authors conclude that the leukocyte esterase test is as accurate as sediment microscopy in identifying urine specimens from infants and children harboring less than 10(4) or less than 10(5) cfu/ml.

Systemic membrane defect and the inhibition of lymphocyte capping in Duchenne muscular dystrophy.

Eight reversible inhibitors were used to study decreases in lymphocyte capping in patients with Duchenne Muscular Dystrophy (DMD) when compared to controls. The inhibitors included hydrocortisone, chlorpromazine, calcium ionophore, Cytochalasin D, propranolol, dibucaine, fluoride and azide. All of these inhibitors disrupt cap formation. Mononuclear leukocytes from DMD patients and controls were isolated from whole blood, incubated with fluorescein-conjugated polyvalent antisera and inhibitor, induced to form caps, and the caps counted using a fluorescent microscope. Cell viabilities and morphology were assessed. After removal of inhibitor, the cells were recounted. All of the inhibitors significantly lowered capping in controls (p less than 0.001), but this effect was seen with only four out of the eight inhibitors in DMD patients. Dibucaine and azide were less inhibitory in patients (p less than 0.005, p greater than 0.05, and p greater than 0.05 respectively) while capping in patients was not inhibited by fluoride and hydrocortisone (p greater than 0.5). The lack of hydrocortisone inhibition suggests that the differences in capping between DMD patients and controls may lie within the membrane itself, rather than its associated components (i.e. cytoskeletal network), and that the defect occurs toward the beginning of the capping sequence.

Rate nephelometry and radial immunodiffusion compared for measuring serum prealbumin.

We compared a rate-nephelometric method and a radial immunodiffusion (RID) assay for measurement of prealbumin (transthyretin) in 55 samples of serum from healthy children. The mean prealbumin concentration as measured by the Beckman Auto ICS nephelometer was 188 mg/L (range 128-350); the mean by RID was 221 mg/L (range 125-419). This difference was statistically significant by Student's t-test (p less than 0.05), but the correlation coefficient (r) was 0.95. To determine a reference interval for prealbumin in children by the Auto ICS method, we assayed samples from 93 healthy children between the ages of one day and 18 years (55 boys, 38 girls). The mean was 191 mg/L, the reference interval (mean +/- 2 SD) 109-273 mg/L. There was no significant difference in prealbumin concentrations between girls and boys (Student's t-test, p greater than 0.05). Evidently the Beckman Auto ICS method measures prealbumin in serum rapidly and accurately.

Determination of a reference range for whole blood serotonin in a pediatric population using high pressure liquid chromatography with electrochemical detection.

Whole blood serotonin (5HT) concentrations were measured in a group of children and adolescents to determine a reference range for this population. Blood was collected after at least a 6-hour fast, mixed with ascorbic acid and EDTA, and frozen at -70 degrees C until analysis. 5HT was determined by HPLC with electrochemical detection. Matrix-matched whole blood standards and controls were used to determine 5HT concentrations, and monitor performance of the assay. 5HT concentrations in boys ranged from 0.53 to 3.13 mumol/L (mean = 1.27, SD = 0.47) while the range for girls was 0.63 to 2.46 mumol/L (mean = 1.21, SD = 0.47). There was no significant difference in 5HT concentrations between boys and girls, nor was there any significant change in 5HT concentration with age. The nonparametric central 95 percent reference range for boys and girls was determined to be 0.64-2.45 mumol/L.

Rhabdomyolysis: two pediatric case reports.

We report two pediatric cases of rhabdomyolysis. This disease involves the destruction of skeletal muscle, which can present with myalgia and a brown-pigmented urine. The first patient presented with acute renal failure, hypertension, and hyponatremia. The second patient was pyrexic, hypernatremic, and hypokalemic, and later developed hypertension. Evidence of rhabdomyolysis in both patients included dark, o-tolidine-positive urine, granular casts in the urinary sediment, and grossly increased activities of creatine kinase (greater than 60 000 U/L) in serum. An uncommonly recognized entity in the pediatric age group, rhabdomyolysis often presents as an acute disease with severe onset but can be diagnosed with relatively simple laboratory tests.

Blind evaluation of lymphocyte capping in Duchenne muscular dystrophy.

Recently, Pickard et al reported decreased "capping" in lymphocytes from patients with Duchenne type muscular dystrophy (DMD) as well as female carriers of the DMD trait. To resolve subsequent debate about the reproducibility of this finding, we carried out a "blinded" collaborative study designed to eliminate the possibility of observer bias. Blood samples from DMD patients, their mothers, and controls were obtained and coded at Johns Hopkins and transported to the Medical College of Virginia, where lymphocyte capping was tested using FITC-labeled polyvalent anti-human immunoglobulin. Diminished capping in lymphocytes was found in 12 of 13 DMD patients (17 of 18 blood samples) and in 14 of 17 mothers of DMD patients (19 of 23 blood samples), as compared with 8 of 21 control subjects (8 of 22 blood samples). The results in both the patient and the carrier groups differed significantly from those in the control group, confirming previous observations of diminished lymphocyte capping in DMD. The findings provide support for the concept of a systemic defect associated with cell membranes in this disorder. The relatively high incidence of false positive results limits the usefulness of lymphocyte capping as a diagnostic test for carriers under the conditions of this study.

Are reference limits for serum creatine kinase valid in detection of the carrier state for Duchenne muscular dystrophy?

We evaluated serum creatine kinase (CK) as an index to heterozygosity in Duchenne muscular dystrophy. When the 97.5th percentile of the CK normal reference interval was selected as the cutoff point, only 31% of 28 obligate carrier mothers and 24% of 43 mothers of simplex cases (those with only one occurrence of dystrophy in the kindred) exceeded this cutoff value. The outcome depended to some degree on the method used for establishing the reference limit for 379 presumably non-carrier, ambulatory women. The considerable overlap of CK activities between the control and carrier population as well as the non-gaussian distribution of the data permitted no satisfactory approach for differentiating these two populations. Neither the application of likelihood ratios, which evaluates a continuum of results without the dichotomy of a cutoff point, nor the application of predictive value based on sensitivity and specificity, which involves use of a cutoff value for decision making, provided a reliable estimate of carrier status. There was no significant difference (2 alpha = .19) between the median CK activity of obligate carrier mothers and mothers of simplex cases. The serum CK test does not provide data that either support or reject the Haldane hypothesis.

The contribution of assays for lymphocyte capping and creatine kinase to detection of the Becker-type dystrophy trait.

Members of three unrelated families with the mild Becker type of muscular dystrophy were subjected to lymphocyte capping tests and measurements of serum creatine kinase activity. Both tests correctly identified all nine affected males, but only the capping test was abnormal in seven of eight obligate carriers. The number of capped cells in carriers and affected persons with the Becker-type dystrophy was generally intermediate between those observed for individuals with the Duchenne trait and normal controls, thus potentially aiding in the differential diagnosis between the two myopathies. The lack of sensitivity of measurements of serum creatine kinase activity in identifying carriers is further complicated by the difficulty of establishing reliable reference intervals for this enzyme in 204 healthy controls. Detailed directions for the performance of the capping test are presented.