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Biomedical subjects

W B Hanley

Publications and source records attributed to W B Hanley.

At least 37 records · Page 2Linked to original sources
PubMed1993

Low iron stores in infants and children with treated phenylketonuria: a population at risk for iron-deficiency anaemia and associated cognitive deficits.

A retrospective study of 53 patients with phenylketonuria (PKU), whose disease was managed with a low-phenylalanine diet, revealed a high incidence of iron depletion (as reflected by subnormal serum ferritin concentrations). Serum ferritin concentrations under 10 micrograms/l were found in one out of six infants aged 5-12 months. Concentrations under 16 micrograms/l were found in 16 of 22 children aged 1-3 years and in 11 of 25 children aged 4-12 years. Dietary iron, estimated from prescribed intakes of medical foods, exceeded the Canadian recommended nutrient intake, suggesting that low stores of iron may be secondary to reduced bioavailability and absorption of iron. These findings suggest that the current dietary management of PKU is associated with an increased risk for low iron stores. Investigators have reported an association in young children between iron-deficiency anaemia and both cognitive and motor disturbances. Children with PKU, already at risk of neurological damage because of phenylalanine neurotoxicity, may be at increased risk as a result of iron depletion. Serum ferritin as well as haemoglobin concentration should be monitored, along with plasma phenylalanine and tyrosine, to ensure optimum treatment of affected children.

Anemia, Hypochromic↗
PubMed1992

Maternal phenylketonuria collaborative study, obstetric aspects and outcome: the first 6 years.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity associated with maternal hyperphenylalaninemia in women of childbearing age with blood phenylalanine levels greater than 240 mumol/L (greater than 4 mg/dl) on an unrestricted diet. STUDY DESIGN: Two hundred thirteen pregnant women with hyperphenylalaninemia that resulted in 134 live births have been enrolled in the study. Outcome measures were subject to the chi 2 test, Fisher exact test, analysis of variance, t test, or Wilcoxon nonparametric test for analysis. RESULTS: Optimal fetal outcome appeared to occur when blood phenylalanine levels less than 600 mumol/L (less than 10 mg/dl) were achieved by 8 to 10 weeks' gestation and maintained throughout pregnancy (trimester averages of less than or equal to 360 mumol/L (less than or equal to 6 mg/dl). Initiation of dietary therapy during the third trimester of pregnancy appears to have little beneficial effect on the fetus. CONCLUSIONS: Preconceptual counseling and early entrance into a prenatal care program is essential in achieving optimal fetal outcome in women with hyperphenylalaninemia.

Congenital Abnormalities↗
PubMed1987

Maternal phenylketonuria (PKU)--a review.

This review points out the very high incidence of damage to the fetus in untreated maternal phenylketonuria (PKU). In classical cases, 92% of the offspring are mentally retarded, 73% have microcephaly, 40% are growth retarded at birth, and 12% have congenital anomalies. Less severe types of PKU and its variants and patients treated with a low phenylalanine diet during pregnancy have a much lower incidence of these defects in their offspring. Very promising results have been obtained in a small number of preconception and early first trimester treated patients under very strict dietary control. Nutrition of the mother and fetus is a major concern during the application of this restrictive diet and must be monitored closely to avoid fetal damage from malnutrition. A 7-year collaborative study of maternal PKU began in November 1984 in the US and Canada, but even in this well publicized study, many patients are presenting late for treatment. It is suggested that premarital and/or prenatal screening for maternal PKU should be initiated for the next generation.

Congenital Abnormalities↗
PubMed1984

Phenylketonuria and its variants: observations on intellectual functioning.

The age at diagnosis, dietary treatment and intelligence quotient (IQ) of 119 patients with phenylketonuria (PKU) and its variants who were under long-term observation were studied. In 27 of the 79 patients with classic PKU the diagnosis had been made and treatment begun late (after 2 months of age). The mean IQ of these 27 patients was 57.6 when they were in their early 20s (although 2 had normal IQs). In contrast, among the 52 patients with classic PKU who were not treated late the mean IQ was 93.6 for the 27 who were still receiving dietary therapy. The mean IQs were 99.3 and 92.7 at ages 5 (when the diet was discontinued) and 15 years respectively for the 12 who had been treated "adequately". It was 76.0 for the 13 who were "over-treated" (malnourished) in the first 6 months of life. Among the patients with atypical PKU, who were treated early, the mean IQs were 110.0 for the 7 who were still receiving dietary therapy and 102.7 for the 12 who were not. The 21 patients with persistent benign hyperphenylalaninemia, who were not treated, had a mean IQ of 104.2. The most important factor in the ultimate IQ of patients with classic PKU is very early diagnosis (by 2 weeks of age) along with immediate initiation of dietary therapy.

Adolescent↗
PubMed1984

Biopterin synthesis defect. Treatment with L-dopa and 5-hydroxytryptophan compared with therapy with a tetrahydropterin.

We have identified a generalized deficiency of monoamine neurotransmitters in a patient with a defect in biopterin synthesis. Neurotransmitter precursors (L-3,4-dihydroxyphenylalanine [L-dopa]; 5-hydroxytryptophan [5-HTP] and a tetrahydropterin [6-methyltetrahydropterin (6MPH4)] were investigated for their ability to normalize monoamine neurotransmitter metabolism. Before treatment, the concentrations of dopamine (DA), norepinephrine, epinephrine, and six monoamine metabolites were very low or undetectable in plasma, cerebrospinal fluid, or urine. L-Dopa and 5-HTP replacement was begun at age 7 mo. This therapy generally corrected the deficiency of monoamines and their metabolites, and improved neurological development until the age of 25 mo. Despite these benefits, the intermittent administration of L-dopa could not produce a stable improvement of acute neurological function or DA metabolism. In the 3 h after L-dopa administration, plasma DA and the motor activity and alertness of the patient rose and fell in parallel. Doses of L-dopa that were clinically optimal produced normal plasma levels of norepinephrine and epinephrine, but excessive concentrations of DA and its metabolites. Furthermore, the clinical and biochemical effects of L-dopa were inhibited by phenylalanine and 5-HTP, respectively, demonstrating that these amino acids have antagonistic pharmacological effects. Physiological correction of the monoamine deficit and the hyperphenylalaninemia of this disorder was attempted at age 35 mo using high doses (8-38 mg/kg per d) of 6MPH4. 6MPH4, a synthetic analogue of tetrahydrobiopterin, controlled the hyperphenylalaninemia. Significant concentrations of 6MPH4 were obtained in the cerebrospinal fluid; no neurological improvement or stimulation of monoamine synthesis in the central nervous system was detected. These findings indicate the complexity in replacement therapy with L-dopa and 5-HTP, but suggest that this treatment may be partially effective in biopterin-deficient patients who are unresponsive to high doses of tetrahydropterins.

5-Hydroxytryptophan↗
PubMed1982

Revision of the Ontario phenylalanine equivalency system and development of a low protein equivalency system.

The Phenylalanine Content of Foods, an equivalency system used in the dietary treatment of phenylketonuria, was prepared in 1975. Recently this system was revised to include a total of 372 food items in various raw and processed states. Food lists are available in a simple version for parents listing the serving size per phenylalanine equivalent, and in a more comprehensive version for dietitians providing weights for the serving sizes as well as values for phenylalanine, protein, and energy per equivalent. Subsequently, the system was modified to form a low protein equivalency system for use in designing low protein diets for a number of other inherited metabolic disorders.

Diet Therapy↗
PubMed1972

Ionized calcium in exchange transfusion with THAM-buffered ACD blood.

In 20 exchange transfusions with THAM-buffered ACD blood 5 ml. of 2% calcium gluconate (8 mg. elemental calcium) was injected after each 100 ml. of blood exchanged. Plasma ionized calcium decreased significantly during the procedure, although after each injection of calcium gluconate, levels returned briefly to normal. Ten minutes after the end of exchange ionized calcium had returned to pre-exchange levels and remained there until at least 30 mins. postexchange.Total calcium also increased significantly. Short periods of extreme hypercalcemia (between 7 and 8 mEq./l.) were noted after each injection of calcium gluconate.The amount of calcium gluconate was insufficient to counteract the calcium-chelating effect of citrate. If no heparinized blood is available we suggest adding heparin and calcium chloride to THAM-buffered ACD blood to avoid the repeated sudden fluctuations between low and high calcium ion activity.

ABO Blood-Group System↗
PubMed1971

The efficacy of dietary therapy for phenylketonuria.

Ninety-four patients with classical phenylketonuria are reviewed. Early treatment with a low phenylalanine diet usually results in normal or near-normal I.Q. Twenty-seven of the 38 patients diagnosed before 2 months of age have an I.Q. in the normal range. Of the other 11, six are dull normal, four are borderline and one is frankly retarded. Adequate reasons are given for the less than optimal results in these 11 early-treated patients. Twenty-one of the 28 patients presenting with abnormal electroencephalograms showed normal tracings soon after initiation of diet and four of the other seven improved. Nine of 12 on continuous anticonvulsant medication at the time of presentation were able to discontinue this soon after institution of dietary measures. Eighteen of the 19 sibling pair comparisons revealed a better ultimate I.Q. in the early-treated sib. A plea for early diagnosis by continuation of newborn screening programs and for centralization of diagnostic confirmation and treatment is made.

Age Factors↗