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Biomedical subjects

G Lockitch

Publications and source records attributed to G Lockitch.

At least 37 records · Page 2Linked to original sources

Renal disease in chronic arthritis of childhood. A study of urinary N-acetyl-beta-glucosaminidase and beta 2-microglobulin excretion.

Urinalyses of randomly obtained samples from children with various types of chronic arthritis revealed proteinuria in 2.3% of patients, hemoglobinuria in 3.5%, erythrocyturia in 4.1%, and leukocyturia in 5.3%; these frequencies are within the range found by screening school children. However, raised urinary levels of N-acetyl-beta-glucosaminidase and/or beta 2-microglobulin (both sensitive measures of renal tubular damage) were found more frequently in children with chronic arthritis than in controls (P less than 0.0001). Abnormalities of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin excretion were associated with active arthritis as measured by physician global estimate of disease activity, with a polyarticular onset of juvenile rheumatoid arthritis, and with the use of slow-acting antirheumatic drugs or the concurrent use of more than 1 nonsteroidal antiinflamtory drug. Abnormal renal tubular function appears to be common in chronic arthritis of childhood. The long-term consequences of this abnormality remain to be elucidated.

Acetylglucosaminidase↗

Biochemical investigation of a child with molybdenum cofactor deficiency.

A girl aged eight months, who presented with developmental delay and dislocated optic lenses, was diagnosed as having combined sulfite oxidase and xanthine dehydrogenase deficiencies consistent with molybdenum cofactor deficiency. The diagnosis was confirmed by demonstrating the absence in urine of urothione, a molybdenum cofactor metabolite. Prenatal diagnosis excluded the disease in the mother's second pregnancy. A summary of an in vitro study of molybdenum cofactor synthesis in the patient is given.

Coenzymes↗

Cardiomyopathy associated with nonendemic selenium deficiency in a Caucasian adolescent.

We describe a girl aged 17 y who died after a cardiac arrest secondary to septic shock. At autopsy, the enlarged, soft, and flabby heart showed microscopic evidence of acute myocardial infarction, myocardial edema, myocardiocyte loss, replacement fibrosis in the interventricular septum, and right and left ventricular hypertrophic nucleomegaly. The pathological diagnosis was that of cardiomyopathy due to prolonged selenium deficiency. The patient had been on total parenteral nutrition for 17 mo, following extensive bowel resection for intractable pain, nausea, and vomiting caused by chronic idiopathic intestinal pseudoobstruction. Seven months before death, when severe biochemical selenium deficiency was diagnosed, supplemental selenium was added to the infusion, and plasma selenium concentrations increased. In long-standing selenium deficiency, sepsis may contribute the final insult to a damaged myocardium, triggering symptomatic cardiac failure and sudden death.

Adolescent↗

Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc.

To determine whether orally administered zinc supplements could correct the abnormal humoral and cell-mediated immunity of Down syndrome, we randomly assigned 64 children with Down syndrome, aged 1 to 19 years and living at home, to receive either zinc gluconate or placebo daily for 6-month periods with crossover from one regimen to another. Control subjects were siblings and age-matched, unrelated children. Serum zinc, copper, and measures of immune system competence were tested at 3- or 6-month intervals. Parents kept daily logs of clinical symptoms such as cough and diarrhea and of physician visits. Mean serum zinc concentrations increased to about 150% of baseline during zinc supplementation, but we found no effect on serum levels of copper, immunoglobulins, or complement; on lymphocyte number or subset distribution; or on in vitro response to mitogens. Children with Down syndrome who were receiving zinc had a trend toward fewer days or episodes of cough and fever but no change in other clinical variables. Long-term, low-dose oral zinc supplementation to improve depressed immune response or to decrease infections in children with Down syndrome cannot be recommended.

Adolescent↗

Selenium deficiency in low birth weight neonates: an unrecognized problem.

To determine whether selenium deficiency is common among low birth weight infants in our neonatal intensive care unit, we surveyed blood samples from healthy full-term and preterm infants born in our hospital over a 3-month period. Selenium was measured by electrothermal atomic absorption spectrometry. Glutathione peroxidase was measured in plasma by an automated method. Baseline (less than 72 hours postnatal) selenium concentration and glutathione peroxidase activity were significantly lower in low birth weight infants than in full-term babies. Sequential selenium analyses were obtained in 16 sick low birth weight neonates who remained in the intensive care nursery for up to 6 weeks because of lung disease. All were fed parenterally without supplemental selenium, with or without oral intake, for periods varying from 3 to 60 days. All had a marked decrease from baseline selenium levels, and values below the detection limit of our assay were found in seven infants. Selenium deficiency is much more common in small infants than is generally realized, but the clinical significance in neonates is poorly understood.

Bronchopulmonary Dysplasia↗

Selenium: clinical significance and analytical concepts.

Selenium is an essential trace element in humans and animals. Its only established function in humans is the antioxidant activity of glutathione peroxidase, a selenoenzyme. Severe prolonged deficiency may cause a fatal cardiomyopathy. Iatrogenic causes of selenium deficiency include parenteral and enteral nutrition. Low plasma selenium is also found in malabsorption, cystic fibrosis, rheumatoid arthritis, neoplasia, and other varied clinical disorders. Death has resulted from a single massive ingestion of selenium, while chronic excessive intake causes skin, nail, and hair pathology. Extreme geographical variation in population blood and urine selenium levels and a marked age-specific variation in population reference intervals are important factors in understanding selenium nutrition. Nutritional requirements, biological availability, and metabolism are discussed in relation to geographical, age, and method variability. Sampling, processing procedures, and methods for selenium quantitation are reviewed. Selenium content in different biological matrices and reference values for pediatric, adult, and obstetric populations are provided.

Animals↗

Timing of specimen collection is crucial in urine screening of drug dependent mothers and newborns.

We compared results of urine drug analysis with clinical data and history to test the usefulness of peripartum drug screening and to establish guidelines for optimal testing. Urine from 28 mothers and 52 babies was analysed. Drugs not suspected by history were found in 10 mothers and six babies. Results assisted in the management of neonatal withdrawal in three babies. Drugs suspected by history were not found in 11/22 mothers and 23/35 babies. About half of these results were associated with delayed urine collection. In 12/28 mothers, drugs administered in hospital could have confused interpretation of screen results. We conclude that urine drug screening without strict protocols for specimen collection is of limited usefulness for management of drug abuse in pregnancy and neonatal drug withdrawal. We favour testing of maternal urine obtained before drugs are administered in hospital. Neonatal urine, if used, should be collected in the first day of life.

Drug Evaluation, Preclinical↗

Age- and sex-specific pediatric reference intervals: study design and methods illustrated by measurement of serum proteins with the Behring LN Nephelometer.

We analyzed blood from 450 healthy children and adolescents, ages one to 19 y, as well as term and preterm infants, to define age- and sex-specific reference intervals for numerous blood constituents. Reference intervals were derived by using nonparametric methods to determine the 0.025 and 0.975 fractiles. Ten serum proteins were measured with the Behring LN Nephelometer. Girls over 10 years of age had higher concentrations of ceruloplasmin and alpha 1-antitrypsin than other children had. There was no sex-related difference in reference intervals for the other proteins tested. Reference intervals are presented for immunoglobulins G, A, and M, complement fractions C3c and C4, ceruloplasmin, transferrin, alpha 1-antitrypsin, retinol-binding protein, and prealbumin (transthyretin).

Adolescent↗

Direct determination of selenium in serum by graphite-furnace atomic absorption spectrometry with deuterium background correction and a reduced palladium modifier: age-specific reference ranges.

We describe the development of a direct method for determination of selenium in serum by graphite-furnace atomic absorption spectrophotometry with deuterium background correction. We include palladium modifier to stabilize selenium in the presence of a strong reducing agent. Spectral interferences from iron are not evident in this system. Because an analysis requires only 20 microL of serum or plasma, the method is applicable to neonatal populations. At a selenium concentration of 0.75 mumol/L (approximately the mean found in our pre-term infants), the within-run CV is 5.3%. For a concentration of 1.83 mumol/L, which approximates our normal adult mean, within-run and between-run CVs are 2.7% and 3.4%. Accuracy is demonstrated by analytical recoveries ranging from 96% to 102%. We present reference values for pre-term and term infants, and age-specific ranges for infants to adults.

Adolescent↗

Age- and sex-specific pediatric reference intervals for biochemistry analytes as measured with the Ektachem-700 analyzer.

Using the Ektachem-700 multilayer film analyzer, we defined age- and sex-specific reference intervals for 20 analytes in sera from a healthy population of neonates and children ages one to 19 years. Upper and lower normal reference intervals for each analyte were determined by nonparametric methods as the 0.975 and 0.025 fractiles, respectively. Newborns have lower concentrations of total protein and albumin, and higher concentrations of phosphate, bilirubin, and enzymes in serum than older children do. Concentrations of urea, glucose, calcium, phosphate, and bilirubin change rapidly postnatally. Outside the neonatal period, no significant age- or sex-related difference was found for plasma glucose, serum amylase, conjugated or unconjugated bilirubin, or lipase. There was no sex-related difference in reference intervals for albumin, total protein, calcium, phosphate, or urea. However, concentrations of uric acid and creatine kinase are much higher in postpubertal boys than in girls. Alkaline phosphatase values peak later in boys. Except for lactate dehydrogenase and gamma-glutamyltransferase, the reference intervals defined here do not differ strikingly from data derived with use of other analyzers. The age- and sex-related trends are independent of method. However, each laboratory should determine the degree to which these reference ranges can be directly applied to analyses performed with another analyzer.

Adolescent↗

Age- and sex-specific pediatric reference intervals and correlations for zinc, copper, selenium, iron, vitamins A and E, and related proteins.

Age- and sex-specific reference intervals based on the 0.025 and 0.975 fractiles of data derived from a healthy pediatric population are presented for zinc, copper, selenium, iron, ferritin, retinol, alpha-tocopherol, and related analytes in serum. Age was an important covariate for copper, selenium, retinol, and tocopherol, and ferritin in boys. Strong correlations were found between retinol and retinol-binding protein, prealbumin (transthyretin), alpha-tocopherol, and selenium. Tocopherol was highly correlated with both cholesterol and triglycerides. We found no relationship between serum zinc and either retinol or retinol-binding protein. Despite exclusion of children in whom anemia, microcytosis, or variant hemoglobins were found, the 0.025 fractile for iron in several age groups was even less than the concentration considered to indicate poor iron nutritional status.

Adolescent↗

Age-related changes in humoral and cell-mediated immunity in Down syndrome children living at home.

Abnormalities of humoral and cell-mediated immunity have been described in Down syndrome but reported findings have been inconsistent. Confounding factors have included age, institutional versus home life, hepatitis B antigenemia, and zinc deficiency. To clarify this problem, we studied 64 children with Down syndrome (DS) compared with an age-matched control group. All children had always lived at home. All the DS children were negative for hepatitis B surface antigen. Serum zinc concentration in the DS group was on average 12 micrograms/dl lower than age-matched control children. They also had significantly lower levels of immunoglobulin M, total lymphocyte count, T and B lymphocytes, and T helper and suppressor cells. In vitro lymphocyte response to phytohemagglutinin and concanavalin A was significantly reduced at all ages in the DS group. Lymphocyte response to pokeweed mitogen increased with age in control children but decreased in the DS children. By 18 yr, the mean response for DS was 60000 cpm lower than controls. The DS group had significantly higher concentrations of immunoglobulins A and G than controls and the difference increased with age. Complement fractions C3 and C4 were also higher in the DS group at all ages. The number of HNK-1 positive cells was higher in the DS group than controls at all ages. When hepatitis and institutionalization are excluded as confounding factors, DS children still differ in both humoral and cell-mediated immunity from an age-matched control group.

Adolescent↗

Blood serotonin concentrations and fenfluramine therapy in autistic children.

Whole-blood serotonin concentrations of 31 autistic children, aged 2 1/2 to 16 years, 10 non-autistic retarded children, and 18 children with Down syndrome were measured by a fluorometric method and compared with those of normal children of similar age range. No significant difference in the serotonin concentration per milliliter of whole blood or per 1000 platelets was found between groups for autistic, retarded, or normal children, but the values for those with Down syndrome were significantly lower. A double-blind cross-over study on the effect of fenfluramine versus placebo in seven autistic boys over a period of 8 months demonstrated a significant decrease in blood serotonin levels during the fenfluramine phase in all subjects. Slight improvements were found in short-term auditory memory and some measures of receptive language skills, particularly in children functioning at a high level. There was no significant change in global psychometric measurements of general intelligence during therapy. No adverse clinical effect was observed other than weight loss of 6% in one child. We conclude that fenfluramine may have some selective favorable effects on increasing attention in high-functioning autistic children. Blood serotonin concentration may be followed as an indication of drug compliance during fenfluramine therapy, but does not appear to reflect clinical efficacy.

Adolescent↗

Pulse oximetry advantages in infants with bronchopulmonary dysplasia.

We studied 12 infants with a clinical and radiologic diagnosis of bronchopulmonary dysplasia who were oxygen dependent and older than 30 days. Simultaneous readings of hemoglobin oxygen saturation (SaO2) determined by two pulse oximeters (Nellcor 100, BTI Biox III) and transcutaneous (tc) PO2 (Sensor Medics, Transend) were correlated with SaO2 (Radiometer, OSM 2 Hemoximeter) and PaO2 (Corning 178) measured on blood from an indwelling arterial catheter. For each infant, the fractional inspiratory oxygen (FiO2) was adjusted to obtain three to five sets of data in the range of 70% to 95% SaO2. Fifty-three data points were generated and pooled for analysis. The slope of the regression line generated for the Nellcor 100 was .86; for the BTI Biox III, it was .91; and for the Sensor Medics Transend, it was .55, resulting in average errors of +2.5%, +1.0%, and -29%, respectively, when comparing corresponding transcutaneous and arterial values. When SaO2 was equal to or less than 95%, no infants were hyperoxic. These data confirm reports by others that tcPO2 values do not accurately represent PaO2 values in older infants with bronchopulmonary dysplasia. Pulse oximeters do not require user calibration, and their sensor is unheated so they will not cause skin burns. We conclude that pulse oximetry offers major advantages over tcPO2 measurements in the management of infants with bronchopulmonary dysplasia.

Blood Gas Monitoring, Transcutaneous↗

Prediction of fetal lung maturity by use of the Lumadex-FSI test.

We analyzed amniotic fluid from 91 pregnancies (estimated gestational age range 31 to 41 weeks), using the Lumadex-FSI Fetal Lung Maturity test (Beckman Instruments), and also determining phosphatidylglycerol content, the lecithin/sphingomyelin ratio, and foam stability index by the "shake test," and compared results with newborn outcome. Five of 64 babies born within 72 h of testing developed hyaline membrane disease. Except for the lecithin/sphingomyelin ratio, the predictive value of a negative test was 100% but that of a positive test was less than 50%. Use of all four tests did not offer diagnostic advantage over the use of Lumadex-FSI alone. For the laboratory that infrequently assesses fetal lung maturity, we believe the sealed cassette format of the Lumadex-FSI will permit better quality assurance than the shake test. The Lumadex-FSI test is intended to provide a graded estimate of positive risk for hyaline membrane disease, but more data from different centers and patient populations are needed to establish reliable predictive values.

Amniotic Fluid↗

Serial changes in selected serum constituents in low birth weight infants on peripheral parenteral nutrition with different zinc and copper supplements.

One hundred and five infants of birth weight 2000 g or less who received peripherally administered parenteral nutrition for periods of three or more weeks, were randomly assigned to groups receiving different amounts of zinc and copper supplement. The blood concentrations of zinc, copper, retinol-binding protein, prealbumin, alkaline phosphatase and aspartate transaminase were followed weekly. Mean serum zinc, retinol-binding protein and prealbumin declined significantly over time while alkaline phosphatase rose. Only the group receiving the highest zinc supplement maintained a mean serum zinc concentration within the normal range at seven weeks. No difference in the protein or enzyme concentrations was found between the different zinc supplement groups. No difference was seen in serum copper or ceruloplasmin between copper dose groups although one intravenous supplement was double that of the other.

Alkaline Phosphatase↗