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Biomedical subjects

G Lockitch

Publications and source records attributed to G Lockitch.

At least 19 recordsLinked to original sources

Neonatal hypernatremic dehydration associated with breast-feeding malnutrition: a retrospective survey.

BACKGROUND: Hypernatremic dehydration in neonates is a potentially devastating condition. Recent reports have identified breast-feeding malnutrition as a key factor in its pathophysiology. METHODS: Using a theoretical framework for breast-feeding kinetics, a retrospective chart review of all neonates less than 28 days of age who were seen at either British Columbia's Children's Hospital or the Vancouver Breastfeeding Centre between 1991-1994 was conducted to identify and classify possible causes of breast-feeding malnutrition among neonates who developed hypernatremic dehydration. RESULTS: Twenty-one cases hypernatremic dehydration were identified. Infant weight loss ranged from 8% to 30% of birth weight, and serum sodium levels ranged from 146 mmol/L to 207 mmol/L. In each case, maternal or infant factors (e.g., poor breast-feeding technique, lactation failure following postpartum hemorrhage and infant suckling disorders associated with cleft palate or ankyloglossia) that could interfere with either lactation or breast-feeding dynamics and account for insufficient breast milk intake were identified. INTERPRETATION: Prenatal and in-hospital screening for maternal and infant risk factors for breast-feeding malnutrition combined with early postpartum follow-up to detect excessive infant weight loss are important for the prevention of neonatal hypernatremic dehydration.

Breast Feeding↗

A new mutation (G51C) in the iron-responsive element (IRE) of L-ferritin associated with hyperferritinaemia-cataract syndrome decreases the binding affinity of the mutated IRE for iron-regulatory proteins.

Hereditary hyperferritinaemia-cataract syndrome is an autosomal dominant disorder characterized by a constitutively increased synthesis of L-ferritin in the absence of iron overload. The disorder is associated with point mutations in the iron-responsive element (IRE) of L-ferritin mRNA. We report a new mutation, G51C, identified in two members of a Canadian family, presenting a moderate increase in serum ferritin and a clinically silent bilateral cataract. Gel retardation assays showed that the binding of the mutated IRE to iron-regulatory proteins (IRPs) was reduced compared with the wild type. Structural modelling predicted that the G51C induces a rearrangement of base pairing at the lateral bulge of the IRE structure which is likely to modify IRE conformation.

Adolescent↗

Iron and copper-associated cirrhosis in infants. Acquired metal toxicity or genetic disorder?

Iron and Copper are essential trace elements for growth and development of the human infant but are toxic in excess. Lethal cirrhotic syndromes in the neonate and infant have been associated with both copper and iron overload. The relative importance of underlying genetic susceptibility and acquired excess of iron or copper in the pathogenesis of these chronic metal toxicity states is controversial and both syndromes probably encompass a spectrum of conditions.

Copper↗

Clinical biochemistry of pregnancy.

Major adaptations in maternal physiology and metabolism are required for successful pregnancy outcome. Hormonal changes initiated even before conception significantly alter maternal biochemistry early in pregnancy. Steroid hormones, peptide hormones, and prostaglandins interact to expand blood and plasma volume and modulate the maternal capacity to supply energy and nutrients to the fetoplacental unit. As gestation progresses, reference ranges for the concentration of many biochemical parameters change significantly from those found in the nonpregnant state. Gestation-specific reference ranges are essential for correct interpretation of tests used in screening, diagnosis, and monitoring during pregnancy. The use of clinical laboratory tests in the management of high-risk pregnancy are discussed from the perspective of testing before conception and during pregnancy.

Adaptation, Physiological↗

Trace elements in pediatrics.

This review discusses biologic roles, metabolism, and clinical aspects of three essential trace elements, zinc, copper, and selenium. Clinical situations that result in disturbed trace element metabolism, and signs or symptoms that may suggest a trace element problem are listed. Important issues for trace element assay development are emphasized, and examples of pediatric reference ranges provided.

Copper↗

Blood lead levels in children aged 24 to 36 months in Vancouver.

OBJECTIVES: To determine the blood lead levels in children and to identify risk factors for elevated levels. DESIGN: Cross-sectional study. SETTING: Vancouver. PARTICIPANTS: Random sample of children aged 24 to 36 months, born and still resident in Vancouver. The sample was stratified proportionally by the median annual family income in the census tract where each family resided. OUTCOME MEASURES: Blood lead levels and risk factors for elevated blood lead levels, determined from a questionnaire administered to parents. RESULTS: Of the children in the sample, 42% (178/422) were ineligible or could not be located. Of the remaining children, 73% (177/244) participated and adequate blood specimens were obtained from 172. The mean blood lead level was 0.29 mumol/L (standard deviation 0.13 mumol/L). (A blood lead level of 1 mumol/L is equivalent to 20.7 micrograms/dL.) The lowest level was 0.06 mumol/L, and the highest was 0.85 mumol/L. Of children with adequate samples, 8.1% (14/172) had blood lead levels of 0.48 mumol/L or higher, and 0.6% (1/172) had a level higher than 0.72 mumol/L. The logarithms of the levels were normally distributed, with a geometric mean (GM) of 0.26 mumol/L (geometric standard deviation 1.56). Of approximately 70 possible predictors of blood lead levels analysed, those that showed a statistically significant association (p < 0.05) with increased blood lead levels were soldering performed in the home as part of an electronics hobby (GM blood lead level 0.34 mumol/L, 95% confidence interval [CI] 0.27 to 0.39 mumol/L), aboriginal heritage (GM blood lead level 0.33 mumol/L, 95% CI 0.28 to 0.39 mumol/L), dwelling built before 1921 (GM blood lead level 0.32 mumol/L, 95% CI 0.28 to 0.37 mumol/L), age of water service connection to dwelling (predicted blood lead level 0.00087 mumol/L [95% CI 0.00005 to 0.00169 mumol/L] higher per year since service connection) and decreased stature (predicted blood lead level 0.018 mumol/L [95% CI 0.0353 to 0.0015 mumol/L] higher for every standard deviation below the age-specific mean height). CONCLUSIONS: This study found much lower blood lead levels in children than those found in previous Canadian studies. The authors believe that this result is not an artefact due to differences in population sampling or methods of collection of blood specimens. The study showed no clear risk factors for elevated blood lead levels: although a few factors had a statistically significant association with increased blood lead levels, the differences in levels were small and unimportant.

Age Factors↗

Fetal fibronectin improves the accuracy of diagnosis of preterm labor.

OBJECTIVE: Our purpose was to assess the utility of cervicovaginal expression of fetal fibronectin in the diagnosis of preterm labor. STUDY DESIGN: Women seen between 24 and 34 weeks' gestation with symptoms of preterm labor, intact membranes, and cervical dilatation < 3 cm were enrolled at five university medical centers. Cervicovaginal swabs were obtained and assayed for the presence of fetal fibronectin by means of a monoclonal antibody assay. Results were compared with cervical dilatation and uterine contraction frequency as indicators of interval to delivery and delivery before 37 weeks. RESULTS: A total of 192 eligible women at a mean gestational age of 30.8 +/- 2.9 weeks were enrolled from a population of 418 subjects screened. The rate of preterm birth was 32.3% (62/192). The mean interval from presentation to delivery was 25.3 +/- 24.1 days in the 45 subjects with a positive fibronectin assay and 52.4 +/- 24.8 days in the 147 subjects with a negative assay (p = 0.0001). The sensitivity, specificity, and positive and negative predictive values of fetal fibronectin expression for delivery < 37 weeks were 44% (27/62), 86% (112/130), 60% (27/45), and 76% (112/147). The fetal fibronectin assay was especially useful in predicting risk of delivery within 7 days (sensitivity 93% [13/14], specificity 82% [146/178], positive predictive value 29% [13/45], and negative predictive value 99% [146/147]) and was notably superior to both cervical dilatation > 1 cm and contraction frequency greater than or equal to eight per hour (sensitivities 29% and 42%, specificities 82% and 67%, positive predictive values 11% and 9%, and negative predictive values 94% and 94%, respectively. CONCLUSION: Cervicovaginal fetal fibronectin predicts delivery within 7 days more accurately than do cervical dilatation and contraction frequency in a population of women evaluated for early preterm labor.

Adult↗

Trace elements in nutrition for premature infants.

Ten trace elements that are nutritionally essential include: zinc, copper, selenium, chromium, manganese, molybdenum, cobalt, fluoride, iodine, and iron. This article briefly reviews the biochemistry of these trace elements, describes clinical deficiency states, and provides a rationale for recommended enteral and parenteral intakes for preterm infants.

Copper↗

Beyond the umbilical cord: interpreting laboratory tests in the neonate.

Interpretation of biochemical testing in the neonatal period is challenging because of the complexity of perinatal physiology, the difficulty of establishing appropriate laboratory reference ranges, and the technical aspects of analyzing microvolume specimens that are often hemolyzed, lipemic, or have a high hematocrit or bilirubin concentration. Metabolic problems such as hyperbilirubinemia and hypoglycemia in the full-term neonate occur as the infant adapts from an intrauterine metabolism to extrauterine life. Pathophysiological processes in the premature infant vary with the severity of prematurity and the immaturity of metabolic systems. Interpreting neonatal biochemistry requires age- and gestation-specific reference ranges but technical, ethical, and philosophical concerns continue to impair the development of the needed reference data.

Clinical Laboratory Techniques↗

Perspectives on lead toxicity.

Lead toxicity causes hematological, gastrointestinal, and neurological dysfunction in adults and children. Symptoms are usually noted with blood lead greater than 1.93 mumol/L. Severe or prolonged exposure may also cause chronic nephropathy, hypertension, and reproductive impairment. Lead inhibits enzymes; alters cellular calcium metabolism; stimulates synthesis of binding proteins in kidney, brain, and bone; and slows nerve conduction. Less severe exposure to lead, designated by blood lead levels of 0.48-0.96 mumol/L, has been implicated in poor pregnancy outcome, impaired neurobehavioral development, reduced stature in young children, and higher blood pressure in adults. Biochemical and systemic effects of high and low level lead toxicity are described. Dust, water, and paint chips are still major sources of lead but lead from folk remedies, cosmetics, food supplements, food preparation utensils, and improperly prepared infant formula has caused epidemic and sporadic severe lead toxicity. Screening for pediatric low level lead exposure requires measurement of blood lead.

Adult↗

Influence of maternal factors on cord and neonatal plasma micronutrient levels.

The influence of gestational length, maternal prenatal supplement and maternal levels on umbilical cord and neonatal plasma selenium, alpha-tocopherol, and retinol were studied and appropriate reference intervals for ongoing studies of gestational and perinatal micronutrient requirements were derived. We measured retinol, alpha-tocopherol (total and alpha-tocopherol:cholesterol ratio), selenium, and glutathione peroxidase in 160 umbilical cord samples and 58 paired maternal and neonatal samples collected on the third postpartum day. Selenium and glutathione peroxidase were also measured in 25 paired umbilical artery and vein samples. The strongest correlation with gestational age and birthweight was found for the cord blood variables, whereas levels in maternal blood were not related to either gestation or weight. Neonatal values were significantly lower than maternal for selenium (0.96 [0.25] compared with 1.56 [0.27] mumol/liter), retinol (0.54 [0.19] and 1.26 [0.45] mumol/liter), alpha-tocopherol (11.5 [3.63] and 32.4 [9.20] mumol/liter), and glutathione peroxidase (446 [174] and 873 [176] U/liter) but not for the ratio of alpha-tocopherol:cholesterol (5.0 compared with 6.0). Maternal use of tocopherol and retinol supplements did not significantly affect blood concentrations. Maternal plasma selenium levels at term were about 60% of nonpregnant adult females. Selenium concentration and glutathione peroxidase activity did not differ between paired umbilical cord arterial and venous samples. Selenium, retinol, and glutathione peroxidase differed between infants born before or after 37 weeks' gestation.

Birth Weight↗

Perinatal and pediatric nutrition.

Nutritional deficiencies develop rapidly in the very low birth weight infants because of a lack of third-trimester accumulation of fat, minerals, trace elements, and fat-soluble vitamins. Symptomatic zinc deficiency and hypernatremic dehydration may occur unexpectedly in the wholly breast-fed full-term or premature infant, and nutritional adequacy should be carefully monitored even in breast-fed full-term infants.

Dietary Carbohydrates↗

Thiamine, riboflavin, and pyridoxine deficiencies in a population of critically ill children.

The unexpected autopsy finding of Wernicke encephalopathy in three children who died after prolonged enteral feeding prompted us to examine the incidence of thiamine deficiency in three high-risk pediatric populations. We also measured riboflavin and pyridoxine activity in the same groups. We used activated enzyme assays (erythrocyte transketolase, glutathione reductase, aspartate aminotransferase) to assess tissue stores of the dependent vitamin cofactors (thiamine (vitamin B1), riboflavin (vitamin B2), and pyridoxine (vitamin B6), respectively). Using our own reference ranges based on data from 80 healthy adults and children, we prospectively investigated the B vitamin status of three groups of children: (1) 27 patients who were fed solely by nasogastric tube for more than 6 months, (2) 80 children admitted to a pediatric intensive care unit for more than 2 weeks, and (3) 6 children receiving intensive chemotherapy. The upper limits for stimulated enzyme activity in control subjects were unaffected by age or gender (16% for transketolase, 63% for glutathione reductase, 123% for aspartate aminotransferase). Using these limits, 10 (12.5%) of 80 patients receiving intensive care and 4 of 6 patients receiving chemotherapy were thiamine deficient. Elevated levels returned to normal after thiamine supplementation. No patients were pyridoxine deficient, but 3 (3.8%) of the 80 patients receiving intensive care and 1 of the 6 patients receiving chemotherapy were also riboflavin deficient. We conclude that unrecognized thiamine deficiency is common in our pediatric intensive care and oncology groups. This potentially fatal but treatable disease can occur in malnourished patients of any age and is probably underdiagnosed among chronically ill children. Our findings may be applicable to other high-risk pediatric groups.

Adolescent↗

Rapid, semi-quantitative assay of C-reactive protein evaluated.

We evaluated a new rapid semi-quantitative immunometric assay of C-reactive protein (CRP) as a screening test for sepsis by comparison with an automated nephelometric method. Plasma samples (n = 101) from preterm infants during the first week of life were saved for CRP analyses. We measured CRP by the Nycocard semiquantitative method and compared the results with those obtained with a Behring Nephelometer. A CRP value less than 10 mg/L was considered to be negative for infection. All CRP results read as less than 10 mg/L (negative) by the Nycocard method were also less than 10 mg/L by the comparison method, and all CRP values found to be greater than 20 mg/L (positive) by the Nycocard method were also positive by the comparison method. Results in the 10-20 mg/L range were considered equivocal. We conclude that the Nycocard CRP semi-quantitative method is a rapid and useful screening test for sepsis in preterm infants.

C-Reactive Protein↗

Improved sample preparation for accurate determination of low concentrations of lead in whole blood by graphite furnace analysis.

The effect of low concentrations of lead on pre- and post-natal growth and development is a current concern. We describe a simple method of sample preparation for direct determination of lead in whole blood by Zeeman graphite-furnace atomic absorption spectrometry. This procedure improves analytical precision and accuracy of lead determinations at low concentrations as compared with published furnace data. At blood lead concentrations of 0.25, 1.98, and 3.76 mumol/L, within-run CVs were 3.2%, 1.8%, and 1.4% respectively; between-run CVs were 7.3%, 2.9%, and 2.2%. Accuracy, as demonstrated by analytical recovery, ranged from 99% to 102%. Our reproducibility/accuracy score in the 1989 Quebec interlaboratory comparison program was 96% compared with the target, second best of 66 participating laboratories.

Adult↗

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↗