Metabolic consequences of trichopoliodystrophy.
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Biomedical subjects
Publications and source records attributed to W E Dodson.
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Valproic acid concentrations correlate with dose in children when sampling times are consistent. Both interpatient variability and average clearance of valproic acid are inversely related to age. Young children usually need higher doses to achieve the same blood levels as other patients, but the levels that result from a dose are less predictable from one child to the next. Whereas valproic acid therapy had little effect on the serum glutamic oxaloacetic transaminase (SGOT), 12% of patients had abnormal SGOTs during an average of 14 months' therapy. The abnormal SGOTs from patients without serious hepatic dysfunction overlap many of the abnormal values in cases of fatal hepatic failure associated with valproic acid.
Infant mice (2 to 4 days old) received valproate (100 or 200 mg per kilogram body weight) subcutaneously once daily for 5 days. Both dosages decreased plasma beta-hydroxybutyrate levels to about one-third of the control value, in the face of normal free fatty acid and glycerol levels. At 200 mg per kilogram of valproate, there were significant decreases in brain weight and brain K content. Both doses produced metabolite changes in brain compatible with a reduced metabolic flux through the glycolytic pathway and the citric acid cycle. Valproate reduced brain aspartate but did not increase brain GABA levels in infant mice. At 200 mg per kilogram of valproate, brain glutamate decreased and taurine levels increased. Two hundred milligrams per kilogram of valproate caused a profound reduction of liver glycogen stores. The apparent decrease in cerebral metabolic rate, reduced glutamate and aspartate, and increased levels of taurine in brain may relate to the anticonvulsant action of valproate. Together with the decreased brain weight and K content, the findings are also compatible with maturational delay. Decreased ketonemia and liver glycogen content may relate to the hepatic toxicity associated with valproate administration in infants and children.
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Infants and children taking phenytoin by mouth every 12 hr had relatively little fluctuations in serum levels measured every 4 hr after a dose. As the average level rose, the relative fluctuation in level was reduced, consistent with nonlinear elimination kinetics. Levels 8 hr after the dose had the least variability and were 104% of the average level over the 12-hr period.
The effect of phenytoin (PHT) concentration on the elimination rate of PHT was evaluated in infants, children, and young adults ranging in age from 1 day to 22 years. As PHT concentration increased, the effective half-life (t50%) increased. In eight children, age 7 months to 4.83 years with initial concentrations between 10 to 20 mg per liter, the average t50% (18.6 hours) was approximately 58% as long as the average in adults with comparable concentrations. Whereas the t50% correlated with the initial PHT concentrations, there was no correlation overall between t50% and age, size, or number of other antiepileptic medications taken. The concentration-dependence of the t50% provided the basis for less frequent dosing than one would expect from previous studies of PHT half-life in children with low concentrations.
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Seven infants developed mepivacaine intoxication secondary to accidental injection during paracervical or pudental blocks or both. All presented with unexplained neonatal depression at birth, tonic seizures (often with apnea) within six hours, and characteristic neurologic findings. Twenty-four-hour urinary excretion produced 12.7 to 37.4 mg, exchange transfusions less than 1.02 to 3.5 mg, and gastric drainage or lavage or both 0.63 to 1.26 mg of mepivacaine. Thus promotion of urinary excretion is the treatment of choice. All six survivors are seizure free and neurologically and developmentally normal at one to 4 1/2 years. With early diagnosis and prevention of severe perinatal hypoxia, the prognosis from intoxication alone is very good.
Two patients with systemic lupus erythematosus, including one with neuropathologic findings, had recurrent multifocal neurologic dysfunction and hyperlipoproteinemia. The lipoprotein disturbances were complex and variable over time. Deficient lipoprotein lipase was found in both patients and appeared to be related temporally to neurologic deterioration. One of these patients had neurologic disease and lipoprotein abnormalities 2 1/2 years before SLE could be documented serologically. These studies suggest that lipoprotein lipase deficiency may be a marker for the endothelial disorder causing cerebral vasculopathy in SLE.
Serum and milk concentrations of caffeine were measured in 5 breast-feeding mothers after a standardised oral dose of caffeine. Peak concentrations of caffeine in serum and milk were attained 60 minutes later. Binding of caffeine by constituents of serum and breast milk was low (25 and 3.2% respectively). In breast milk, caffeine binding is associated with the cream layer, and correlates with the butter fat content. Caffeine does not diffuse freely into breast milk and concentrations in milk are lower than in maternal serum.
Three patients with subacute sclerosing panencephalitis (SSPE)--two with acute disease and one with an exacerbation--had abnormal radionuclide brain scans during periods of rapid neurologic deterioration. In two of the three patients radionuclide brain scan showed lesions of both cortex and deeper structures, indicating the panencephalic nature of the disease. There was no contrast enhancement on computerized tomography (CT) in the areas of radiopharmaceutical accumulation in the two patients studied. We feel that delayed radionuclide scanning is more sensitive in detecting acute SSPE than routine contrast-enhanced CT, because more time is allowed for tracer accumulation in lesions and for background activity to decrease.
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Bathing with soap containing hexachlorophene was instituted during two major staphylococcal epidemics in a Neonatal Intensive Care Unit. Infants who weighed less than 1,200 gm, those with a postconceptional age of less than 35 weeks, and those with large areas of abraded skin were at highest risk to achieve elevated blood HCP concentrations. T 1/2 of HCP ranged from 6.1 to 44.2 hours and appeared to follow first order kinetics. Time of peak blood concentrations of HCP following a bath ranged from 6 to 10 hours. One infant with liver disease achieved a concentration of HCP of 4,350 ng/ml after seven baths and developed clinical symptoms consistent with HCP toxicity.
A case of Maffucci's syndrome with cutaneous, bony and neurological complications is reported. The patient had lymphangiomatosis at birth and developed multiple cutaneous haemangiomas and osteochondromas during childhood. She also developed multiple neurological defects, including cranial nerve palsies due to an intracranial osteochondroma. The occurence of mesodermal dysplasias and neoplasias in the Maffucci syndrome is emphasized, and it is suggested that there is a close relationship between this disorder and Ollier's disease (multiple enchondromatosis).
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We describe a micromethod for measuring hexachlorophene by use of gas-liquid chromatography with a 63Ni electron capture detector. The procedure requires 100 micronl of blood for extractions of hexachlorophene, and dichlorophene is added as an internal standard. CV is 3.4% over the concentration range of 500 to 1300 microng of hexachlorophene per liter of whole blood. This procedure permits repeated measurements of hexachlorophene in newborns who are being washed with soap containing hexachlorophene.
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