Treating attention-deficit hyperactivity disorder: medication and behavior management training.
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Biomedical subjects
Publications and source records attributed to J V Murphy.
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Seizures are more common in children than in adults. Since most pediatric epilepsies can be controlled with a single antiepileptic drug, children with epilepsy should receive monotherapy when possible or switch from polytherapy to monotherapy. More than half of the epileptic patients receiving multiple antiepileptic drugs will have better seizure control as well as fewer side effects with monotherapy. Most of the pediatric epilepsies occur as primary generalized seizures, for which valproate is a preferred drug. Children can begin to receive valproate treatment in a dosage of 20 to 30 mg/kg per day in two or three divided doses. After several days, plasma levels may be useful in adjusting the dosage. The major adverse effect of valproate in children is fatal hepatotoxicity. The risk of this complication is considerably lower with valproate monotherapy (one per 10,000 patients) than with polytherapy. Other advantages of valproate monotherapy, compared with polytherapy, include the avoidance of drug interactions, lower cost, and reduced potential for impaired cognitive function, which is particularly important in children.
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The mother-child interactions of 60 hyperactive children subdivided equally into five age levels (years 5, 6, 7, 8 and 9) were studied during free play and task periods in a double-blind drug-placebo evaluation of two dose levels of Ritalin (0.3 and 0.7 mg/kg bid.) on these interactions. No effects for age or drug condition were found during free play. In contrast, age effects were significant in the task period with the children increasing their compliance and sustained attention with age. In response, mothers decreased their direction and control while increasing their passive observation of the children. Several drug effects were found during the task period, indicating that only the high dose of Ritalin produced improvements in child compliance. However, both doses resulted in decreases in mothers' controlling reactions to the child's compliance and off-task behavior as well as in ratings of home behavior problems. Drug effects were essentially the same across all five age levels. The interaction patterns of hyperactive children are similar to those found in younger normal children in previous research, apparently reflecting a chronic lag in this pattern in hyperactive children that may be improved with stimulant medication.
Tubuloreticular inclusions (TRI) have been observed in the rough endoplasmic reticulum of blood lymphocytes and monocytes in two cases of Reye's syndrome initiated by influenza infections. Tubuloreticular inclusions are seen in these mononuclear leukocytes during the acute phase of illness, but not during convalescence. Since TRI have been demonstrated in peripheral mononuclear leukocytes in patients with acquired immunodeficiency syndrome, systemic lupus erythematosus, and certain viral infections including T-cell leukemia, it may be that the finding of TRI in Reye's syndrome reflects a viral infection and/or immune dysfunction, if such association is not proved to be fortuitous.
Twenty-two patients with recurrent seizures that started less than 24 hours after immunization with diphtheria, tetanus, and pertussis (DTP) vaccine were retrospectively studied. The initial seizure generally occurred after one of the first three DTP vaccine immunizations, and followed that immunization by less than 12 hours. Two of the 22 patients were siblings. Eight patients had additional immunizations with DTP vaccine and four had immediate worsening of their seizures. Of the 22 patients, only one was seizure free and stopped taking anticonvulsants. Three patients exhibited normal development, and 11 had severe developmental delays. Based on these observations, we reviewed current contraindications for immunization with pertussis vaccine.
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Sixty-one newly diagnosed epileptic patients with generalized tonic-clonic, clonic, or tonic seizures were randomly allocated to treatment with valproate (VPA) and phenytoin (PHT). After 6 months, both drugs had been effective in preventing recurrence of seizures. Seventy-three percent of patients receiving VPA and 47% of patients receiving PHT had no recurrences. Side effects of either drug were mild. Laboratory abnormalities were similar for both drugs. Except for one PHT patient with toxic hepatitis, therapy was not discontinued.
Ultrastructural abnormalities in two stepbrothers with Hunter's syndrome, ages 1 and 4 years, were found in cortical neurons, neurons of the myenteric plexus, and skin. Inclusions containing little or no electron-dense material were noted in most tissues, and lamellar figures were restricted to cortical neurons and neurons of the myenteric plexus. These changes correlate with those described in tissues obtained at post mortem.
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To determine the frequency of hyperammonemia in asymptomatic patients receiving valproic acid, plasma ammonia concentrations were measured in 55 patients receiving this drug and in 12 patients receiving other anticonvulsants. Twenty-nine of the 55 patients receiving valproic acid and none of the control patients had plasma NH3 levels above the normal range. Ten of the 11 patients receiving both valproic acid and phenytoin sodium in combination had elevated NH3 levels, as did five of six patients receiving both valproic acid and phenobarbital sodium. Elevations in plasma NH3 levels, as high as 140 mumole/L, were well tolerated, and valproic acid dose reductions were not necessary. Based on our findings, hyperammonemia is not an indication for reducing or eliminating valproic acid therapy.
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In Fabry disease, as in other X-linked traits, identification of all heterozygotes is difficult. Reduced plasma alpha-galactosidase activities will correctly identify 60-70% of the carriers. The identification rate improves when an alpha/beta-galactosidase activity enzyme ratio is used. We measured alpha-galactosidase activity in reference to several other enzyme activities, beta-galactosidase, beta-hexosaminidase, and alpha-fucosidase in plasma and leukocytes from 22 suspected and 9 obligate carriers from 4 kindreds of Fabry disease patients. Utilizing such ratios or various combinations of ratios in plasma we have correctly identified the carrier state in 91% of heterozygotes. Leukocyte alpha/beta-galactosidase identified one more female than leukocyte alpha-galactosidase activities alone. We recommend the use of such multiple biochemical tests to identify carriers of Fabry disease.
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