The effects of nicotine plus haloperidol compared to nicotine only and placebo nicotine only in reducing tic severity and frequency in Tourette's disorder.

We studied the effects of chewing nicotine gum on tic frequency and severity in 10 patients with Tourette's disorder (TD) on haloperidol, versus 9 untreated TD patients; placebo gum was administered to 5 of these untreated patients. Videotapes of patients during a 2-hr period of 30 min baseline, 30 min gum chewing, and two 30-min postgum-chewing periods were utilized. For those TD patients on haloperidol, significant reductions occurred in tic frequency and severity during the gum-chewing and the two postgum-chewing periods. Nicotine gum alone caused a decrease in tic frequency only during gum-chewing and one postgum-chewing period, while placebo gum showed no effect. In this study, nicotine markedly potentiated haloperidol effects in treating TD, and showed lesser effects on TD when used alone.

Nicotine potentiation of haloperidol in reducing tic frequency in Tourette's disorder.

In an open, nonblind study, 10 patients with Tourette's disorder who were being treated with haloperidol were videotaped before, while, and after chewing nicotine gum. The frequency of tics was reduced significantly during the 30-minute gum-chewing period and during the 1 hour after gum chewing. Nicotine appears to potentiate haloperidol effects in patients with Tourette's disorder.

Treatment of children with phenylketonuria using a phenylalanine-free protein hydrolysate (Albumaid XP).

Albumaid XP, a phenylalanine-free protein hydrolysate, was used for treatment of five phenylketonuric infants born between January, 1970, and September, 1972. The results were compared with those obtained from the five infants most recently treated with Lofenalac in our clinic prior to 1970. Treatment was begun by 2 months of age in all instances. Satisfactory physical growth and mental development were achieved using either Albumaid XP or Lofenalac, and there were no major differences in the outcomes with either treatment. The two protein sources may be used interchangeably for treatment of phenylketonuria.

MK-801 prevents hippocampal neurodegeneration in neonatal hypoxic-ischemic rats.

In cerebral asphyxia, enhanced postsynaptic stimulation of N-methyl-D-aspartate (NMDA) receptor by excessive glutamate may mediate neuronal injury and death. The neuroprotective potential of the novel, potent NMDA receptor antagonist MK-801 was assessed by evaluating hippocampal behavioral and histologic outcomes in an experimental rat model of neonatal hypoxia/ischemia. Seven-day-old rats with and without MK-801 pretreatment were subjected to unilateral carotid ligation followed by 2 hours of hypoxia. At age 30 days, spontaneous alternation behavior was measured using a conventional wooden T maze. Hypoxic-ischemic animals pretreated with saline demonstrated a significant impairment in spontaneous alternation behavior compared with that of normal control rats and the hypoxic-ischemic rats pretreated with MK-801. Hippocampal neuronal damage in the CA1 and CA3 regions was prevented in animals pretreated with MK-801 vs saline-treated controls. Therefore, while saline-treated rats with hippocampal lesions showed defective memory and hippocampal neuronal destruction, pretreatment with MK-801 protected rats. Thus, MK-801 appears to protect hippocampal neurons from hypoxia/ischemia and may be potentially beneficial in preventing neonatal asphyxial brain damage.

gamma-Aminobutyric acid in CSF of children with febrile seizures.

Previous studies have suggested that levels of cerebrospinal fluid (CSF) gamma-aminobutyric acid (GABA) may be decreased in children with febrile seizures. We used gas chromatography and mass spectrometry to measure CSF GABA levels in 14 children with febrile seizures. The results were compared with the GABA levels in six children with first-time afebrile seizures, three with recurrent febrile seizures, and 13 controls (febrile children undergoing lumbar puncture to rule out meningitis). Children with central nervous system infections or known neurologic disease were excluded. The CSF GABA levels in children with febrile seizures were not significantly different from those in controls and children with afebrile or recurrent febrile seizures. In the control group, CSF GABA levels correlated with increasing age. There was no correlation with severity of febrile response in any group. The results indicated that the CSF GABA level may not be abnormal in patients with first-time febrile convulsions.

Childhood cerebellar astrocytoma presenting with hemorrhage.

A cerebellar astrocytoma presented with acute intracranial hemorrhage. Computerized tomography and vertebral arteriography defined the tumor and the vascular supply. The tumor was successfully removed. It is important to select the appropriate diagnostic studies so that the rate intracranial hemorrhage masking a brain tumor can be delineated.

Hereditary aplasia cutis congenita and associated defects. Three instances in one family and a survey of reported cases.

Hereditary aplasia cutis congenita (ACC) is a rare, dominantly inherited syndrome of scalp aplasia associated with defects of the underlying skull and absent distal phalanges of the feet. The scalp lesions are generally benign, but the increased risk of bleeding or meningitis may require skin grafting.

Pathological features of the eye in the oculocerebrorenal (Lowe) syndrome.

We studied the eyes of a 13-year-old boy with Lowe syndrome and updated the microscopic ocular findings. These are interpreted as a mesoectodermal dysgenesis involving the anterior and posterior segment. The eye exhibits a greater variety of morphologic change than any other organ in Lowe syndrome. The microscopic findings, particularly in the lens, are highly suggestive of this disorder. The pathogenesis of the ocular and extraocular lesions in Lowe syndrome in unknown. Most of the ocular abnormalities are probably determined in the first two months of gestation and there is no apparent embryologic relation to extraocular abnormalities. Some manifestations of Lowe syndrome may be secondary to accumulation of polyamines, a class of compounds that includes cytotoxic byproducts of faulty dibasic amino acid metabolism.

Alternating hemiplegic migraine in childhood.

Alternating hemiplegic migraine results immediately in an incapacitated state and can lead to long-term deterioration in cognitive and neurological function. In this report, two children with alternating hemiplegic migraine are described. The pathogenesis, precipitating factors, diagnostic tests, treatments and prognosis for alternating hemiplegic migraine are discussed.

Evaluation of a phenytoin dosage regimen design and adjustment computer program.

A computer program for phenytoin (PHT) dosing was developed containing seven different menus: two for drug-naive patients, one using an empirical equation, the other using means for Vmax and Km; two for patients in whom either one or two dose rates and steady-state concentrations are available; two for patients with hypoalbuminemia, and uremia, respectively; and one menu that optimizes Vmax and Km from available steady-state concentrations. The program accepts or converts PHT and sodium PHT, and makes blood level correction for the concomitant administration of 25 different drugs. The evaluation of the program was done by retrospective analysis using data from three study pools: group I involved 47 patients from the University Hospital, group II relied upon 29 patient data supplied from a collaborative Veterans Administration study, and group III involved 26 patients from the Children's Hospital. Predictions were made and compared with found data to be within a range of +/- 15, 20, or 25%. For study group III, many individual blood samples were less than 8 micrograms ml-1; hence, saturation kinetics may not have been involved. It is suspected that saturation kinetics in infants may begin at higher levels. Compliance seems to still be a major problem in PHT monitoring and dosage regimen adjustment. Accepting the data as they are, using one or two dose rates with the corresponding blood concentrations resulted overall in 73-86% achieving blood levels within +/- 25% of the predicted value.