Iris Osberg

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.

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.

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, Dunnetts 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.

Decreased Total Serum Coenzyme-Q10 Concentrations: A Longitudinal Study in Children with Cystic Fibrosis

OBJECTIVE To assess total serum levels of coenzyme Q(10) (Co-Q(10)), an important antioxidant, in children with cystic fibrosis (CF) and to investigate an association between Co-Q(10) level and clinical outcome. STUDY DESIGN Co-Q(10) levels were measured annually in a prospective cohort study of 381 children with CF. A total of 1092 serum levels of total Co-Q(10) were obtained by high-performance liquid chromatography and ultraviolet light detection. Associations of Co-Q(10) with demographic variables and clinical outcomes were investigated. RESULTS Of the 381 initial total serum Co-Q(10) measurements, 188 were in the deficient range. Low Co-Q(10) was significantly more prevalent in patients with pancreatic insufficiency (PI) (55%) compared with patients with pancreatic sufficiency (PS) (3%); 22% of the patients with PI exhibited persistently low Co-Q(10) levels. Low Co-Q(10) levels were significantly associated with Pseudomonas aeruginosa colonization in patients with PI and CF under age 24 months, but not with subsequent lung function or hospitalization rates. Low Co-Q(10) levels were related to other markers of nutritional status, including total lipids, beta-carotene, and alpha-tocopherol. CONCLUSIONS Persistently low total serum Co-Q(10) levels are common in children with CF and PI. A prospective study is indicated to determine whether Co-Q(10) supplementation in CF is beneficial.

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)