Supplementation with carotenoids corrects increased lipid peroxidation in children with cystic fibrosis.

Evidence of lipid peroxidation previously documented in cystic fibrosis (CF) implies an imbalance between free radical generation and antioxidant defense mechanisms. The aim of the present study was to examine the relation between plasma concentrations of malondialdehyde, a marker of lipid peroxidation, and the exogenous antioxidant line of defense. Malondialdehyde concentrations (90.2 +/- 4.7 nmol/L) in 25 children with CF aged 9.6 +/- 0.8 y were higher (P < 0.001) than concentrations (69.1 +/- 2.6 nmol/L) in 17 children used as control subjects and were not correlated with any marker of disease severity. In contrast with their all-rac-alpha-tocopherol status, which was normal as a result of routine supplementation with a 200-mg dose of all-rac-alpha-tocopheryl acetate/d, beta-carotene was very low. A 2-mo open trial in which 12 children with CF aged 11.5 +/- 0.8 y were given 4.42 mg (8.23 mumol) beta-carotene three times per day led to normalization of the malondialdehyde concentration in all but 1 patient, in conjunction with an increase of plasma beta-carotene from 0.08 +/- 0.03 to 3.99 +/- 0.92 mumol/L. Their plasma concentrations were inversely correlated (r = -0.54, P = 0.006) [corrected] with malondialdehyde when the values measured pre- and posttreatment were pooled. We conclude that beta-carotene deficiency contributes to lipid peroxidation in CF and that supplementation may eventually prove to be a useful adjunct for the management of the disease.

Exercise versus overnight albumin excretion rates in subjects with type 1 diabetes.

Diabetic nephropathy is the leading cause of new cases of renal failure in the US and Europe. An elevated albumin excretion rate (AER) on an overnight urine sample is considered an early predictor of end-stage renal failure. An elevated AER on a post-exercise urine sample has previously been considered to be an even earlier marker of renal damage. In a longitudinal prospective study, 373 subjects with insulin-dependent (type 1) diabetes mellitus had a total of 714 renal evaluations, each of which included one exercise and two overnight urine collections for AER determinations. All subjects were at least 13 years old and had diabetes for at least 4 years. There was a strong correlation between exercise and overnight AERs (r = 0.74, P < 0.001). For the 60 subjects with an initial borderline increase of either overnight or exercise AER, the overnight AER values (7.6-20 micrograms/min) progressed first for 52% of subjects whereas the exercise AERs (41-114 micrograms/min) progressed first for 43% of subjects (5% had simultaneous elevations of both). For the 22 subjects in which an abnormal overnight (> 20 micrograms/min) or exercise (> 114 micrograms/min) value was detected first, 17 (77%) had an elevated exercise AER first, whereas only 4 (18%) had an elevated overnight AER first. This study shows that an increase of either the exercise or the overnight AER can occur first, dependent upon the level of abnormality being considered. The two tests correlate closely with one another.(ABSTRACT TRUNCATED AT 250 WORDS)

24-hour ambulatory blood pressure and renal disease in young subjects with type I diabetes.

Twenty-four hour ambulatory blood pressure (ABP) was evaluated in 150 teenage and young adults with insulin-dependent diabetes mellitus (IDDM) to define high-risk subjects who are likely to develop early diabetic nephropathy. Their age range was 16-28 years with diabetes of 3.5-25.8 years duration. All subjects had office blood pressure (BP) measured, wore an ABP monitor for 24 h, and collected two or more timed urine samples for albumin excretion rates (AERs). Eighty-six subjects had no elevation of AER (< 7.6 micrograms/min), 29 subjects had borderline elevations (7.6-20 micrograms/min), 24 subjects had microalbuminuria (20.1-200 micrograms/min), and 11 had macroalbuminuria (> 200 micrograms/min). Age, gender, duration of diabetes, and single office BP readings were similar in the four groups (p > 0.05, logistic regression). All 24-h ABP parameters were significantly higher in subjects with diabetes having AER values greater than 7.6 micrograms/min when compared with healthy age- and gender-matched nondiabetic controls (p < 0.05, Dunnett's t test). The percent of nighttime systolic and diastolic ABP readings above the 90th percentile of normal for age, gender, and race and the percent of readings in the hypertensive range (> 140/90) were significantly related with AERs (p < 0.01; logistic regression). A higher percentage of ABP values above the 90th percentile for age, gender, and ethnic group or of ABP readings above hypertensive levels (> or = 140/90) are associated with diabetic renal disease.

The "eyetone" blood glucose reflectance colorimeter evaluated for in vitro and in vivo accuracy and clinical efficacy.

We evaluated the performance of a blood glucose reflectance colorimeter ("Eyetone," Ames Co.) for accuracy and precision with use of "Dextrostix" (Ames Co.) glucose oxidase reagent strips for blood samples with known and unknown concentrations of glucose covering the usual range of neonatal blood glucose (200-800 mg/L). The meter was calibrated and tested by research nurses and one clinical chemist. Five unknowns were tested for accuracy and precision (56-92 determinations per unknown) and compared with Beckman Astra values (plasma and calculated whole blood). Eyetone/Dextrostix values differed (gave lower values) from the calculated whole-blood values only at concentrations less than 300 mg/L. On 258 clinical specimens from newborn infants, Eyetone/Dextrostix values were not different from calculated whole-blood values (p less than 0.05, r = 0.80). Operator training to develop a consistent procedure was the most critical factor in achieving accurate and precise results.

A solution to the problem of bilirubin interference with the kinetic Jaffé method for serum creatinine.

We measured bilirubin interference with the kinetic Jaffé method for serum creatinine. Both pooled sera with added bilirubin and icteric patients' sera were used and results with of which gave more nearly "true" values.

Borderline increases in albumin excretion rate and the relation to glycemic control in subjects with type I diabetes.

We evaluated "borderline" increases in overnight albumin excretion rates (AERs)----i.e., those between the upper 95th percentile of normal (7.6 micrograms/min) and the lowest value currently considered predictive of nephropathy (30 micrograms/min)----to determine their importance and to see whether glucose control influenced subsequent changes in the "borderline" AER values. Between 1985 and 1990, we studied 190 subjects with insulin-dependent diabetes mellitus (Type I), analyzing a mean of 6.5 timed overnight urine samples collected per subject. Above-normal AERs were associated with a significantly (by ANOVA) higher mean age (P = 0.03), longer duration of diabetes (P = 0.0002), and greater mean glycohemoglobin values (P = 0.002). The transition rate between borderline and abnormal AERs was significantly higher (P less than 0.0001, chi-square test) than the direct transition rate between normal and abnormal AERs, thus showing the borderline AER to be a definite intermediate stage. Good and poor glucose control were clearly associated with improvement and worsening, respectively, of the borderline AER values (P = 0.032, chi-square test of trend). More attention to borderline AER values is clearly indicated.

Airway inflammation in children with cystic fibrosis and healthy children assessed by sputum induction.

A noninvasive method to characterize inflammation and infection in the airways of nonexpectorating children with cystic fibrosis (CF) is needed for clinical and research purposes. Accordingly, we performed sputum inductions by administering 3% saline to 11 healthy control children and 20 children with CF, composed of 7 sputum producers (capable of spontaneously expectorating sputum) and 13 nonproducers. Induced sputum weights were comparable in each group, whereas the amount of induced sputum collected from the CF producers was over 10-fold higher than the spontaneously expectorated samples. We found a significant increase in indices of airway inflammation, including total cell counts, absolute neutrophil counts, interleukin-8 (IL-8) levels, and neutrophil elastase activity in the CF subjects compared with the healthy control subjects. These same indices in the induced sputum specimens from CF producers were significantly correlated with levels in the matched expectorated sputum specimens. Sputum total protein concentration was elevated in the CF groups, whereas urea and albumin levels were not significantly different. Salivary analysis, performed separately, revealed higher levels of IL-8 and total protein in the CF groups. Airway infection, as assessed by quantitative counts of CF-related bacterial pathogens, was also higher in the CF subjects. The same bacterial pathogens, in similar colony counts, were isolated from both the induced and expectorated sputum samples from the CF producers. We conclude that airway inflammation and infection, assessed through sputum induction, are significantly increased in children with CF as compared with healthy children. Furthermore, induced sputum samples are similar to spontaneously expectorated samples in describing both inflammation and infection in the CF airway.

Clinical application of a new glucose analyzer in the neonatal intensive care unit: comparison with other methods.

We evaluated the operation of the Yellow Springs Instrument Co. (YSI) glucose analyzer (model 23A) by clinical nurses for the measurement of blood glucose in the intensive care nursery. In vitro performance was determined with the use of aqueous standards; with a 2-point calibration of 0.0 and 200 mg/dl, a precision of better than 1.0% of each standard (25, 50, 100, 200 mg/dl) was achieved, and the linearity was excellent (Y = 0.99X - 0.49, r = 0.99). The YSI correlated well with a manual spectrophotometric glucose oxidase method (r = 0.99) and the Kodak Ektachem analyzer (r = 0.98) using human umbilical cord blood samples. Five trained clinical nurses performed all YSI and glucose reagent strip analyses, including all in vitro and patient samples. Four reagent strip methods were compared with the YSI from 104 neonatal heel-stick blood samples: Glucometer II with memory (r = 0.73), Glucostix (r = 0.74), Dextrostix (r = 0.70), and Chemstrip bG (r = 0.83). We conclude that clinical nurses can and do learn to use the YSI with excellent precision and that the YSI represents an improved method for measuring glucose concentrations in the newborn intensive care nursery.

Glycemic control and longitudinal testing for exercise microalbuminuria in subjects with type I diabetes.

There is a need for better and earlier markers of clinical renal damage in subjects with Type I diabetes. In this prospective study, exercise albumin excretion rates (AERs) were studied longitudinally for a 4-year period in 187 young subjects with Type I diabetes. For this time period, 54% of subjects continued to have normal overnight and exercise AERs, 11% had continuously elevated exercise and overnight AERs, 11% developed an elevated exercise AER with the overnight AER remaining normal, and 12% had a normal overnight AER throughout the study, with initially elevated exercise levels later decreasing to normal. This improvement in exercise AER was associated with improved glycosylated hemoglobin (HbA1) values for 64% of the subjects (p = 0.0004, paired t test). Five percent of subjects, who initially had only an elevated exercise AER, developed a consistently elevated overnight AER. Seven of these nine subjects showed either worsening (greater than 10%) or no improvement in their HbA1 values from the initial to the final study periods. Five percent of subjects continued to have an elevated exercise and normal overnight AER throughout the study. These results show that the elevated exercise AER represents a definite transitional stage between a normal and an abnormal (greater than 30 micrograms/min) overnight AER. In addition, a "window" exists during which an elevated exercise AER may be reversed by improved glucose control, but if this improvement does not occur, progression to an increased overnight AER is likely to result.

Effects of storage time and temperature on measurement of small concentrations of albumin in urine.

Accurate measurement of albumin excretion rates is important in choosing treatment regimens that may reverse early diabetic renal damage. We report here determinations of slight albuminuria ("microalbuminuria") by radioimmunoassay of fresh specimens, frozen aliquots (stored at -20 degrees C for two, eight, and 24 weeks), and refrigerated specimens (stored at 4 degrees C for one, two, and eight weeks). Seven separate analyses were performed on 101 specimens of urine obtained from 37 subjects with insulin-dependent diabetes mellitus and from 10 nondiabetic healthy controls of a similar age. Storage of urine samples at -20 degrees C resulted in significantly lower measurements of microalbuminuria than in fresh urine (ANOVA, corrected for repeated measures: P = 0.01 to 0.0001). In contrast, storage of urine samples at 4 degrees C for as long as eight weeks did not significantly affect urinary albumin results. The pH values of the specimens were minimally altered and were not a likely cause of the decreased albumin values in the frozen specimens. We conclude that urine specimens for microalbuminuria measurements should either be analyzed as fresh specimens or stored at 4 degrees C and assayed as soon as possible.

Effect of ursodeoxycholic acid therapy on hepatic function in children with intrahepatic cholestatic liver disease.

BACKGROUND: Ursodeoxycholic acid (UDCA) has been shown to improve pruritus, alanine aminotransferase (ALT), and cholesterol levels in children with intrahepatic cholestatic liver disease. However, the effect of UDCA on quantitative tests of hepatic function in children is uncertain. METHODS: A 2.5-year, open label, crossover study, was designed to determine the effect of UDCA (15-20 mg/kg per day for 12 months, off for 6 months, and on again for 12 months) on clinical symptoms, biochemical test results, galactose and caffeine elimination half-lives (t1/2), and quantitative hepatic scintigraphy in 13 subjects aged 13.1 +/- 2.1 years (10 of whom completed the entire study), with intrahepatic cholestasis. RESULTS: Pruritus improved with UDCA in the 6 patients with pruritus on entry into the study. At 12 months, there was a significant decline in ALT, gamma-glutamyl transpeptidase, and plasma levels of copper and manganese, with no further decline in these levels at 24 months. There were no changes in bilirubin or cholylglycine levels. After therapy was discontinued at 12 months, UDCA was restarted within 1 month in 9 of 12 patients in response to a doubling of ALT (n = 6) or worsening pruritus (n = 3). Galactose t1/2 increased after 12 months, with no further increases after 24 months of UDCA therapy, whereas caffeine t1/2 did not change. There were no significant changes in hepatic scintigraphy throughout the study. CONCLUSIONS: These data suggest that although UDCA therapy improves pruritus and results in a reduction in ALT and gamma-glutamyl transpeptidase, UDCA therapy did not improve quantitative measures of hepatic function in children with intrahepatic cholestasis.

A trial of oats in children with newly diagnosed celiac disease.

OBJECTIVE: To determine whether consumption of oats is safe in children with newly diagnosed celiac disease who are starting a gluten-free diet. STUDY DESIGN: We conducted a self-controlled, open-label, 6-month trial of a commercial oat breakfast cereal product. Primary outcome variables were small bowel histomorphology and anti-tissue transglutaminase IgA antibody titer. RESULTS: The 10 children who completed the study were 6.8 +/- 4.0 (mean +/- SD) years of age and 5 were male. Over 6.6 +/- 0.7 months, they consumed 24 grams of oat cereal per day, or 1.2 +/- 0.9 g/kg/d. Compared with start of study, at completion there was a significant decrease in biopsy score (P <.01), intra-epithelial lymphocyte count (P <.005), anti-tissue transglutaminase IgA antibody titer (P <.01), and number of symptoms (P <.01). CONCLUSIONS: We conclude that consumption of a commercially available oat cereal product for 6 months is safe for children with celiac disease beginning a gluten-free diet. Studies are needed to determine the long-term safety of including oat cereal in the gluten-free diet.