Thomas K. Koch

Multicenter trial of d-α-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis

BACKGROUND Malabsorption and deficiency of vitamin E causing neurological degeneration are common consequences of chronic childhood cholestatic liver disease. The objective of this study was to determine the long-term efficacy and safety of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) in correcting vitamin E deficiency in children with chronic cholestasis who were unresponsive to other forms of oral vitamin E. METHODS Sixty vitamin E-deficient children with chronic cholestasis unresponsive to 70-212 IU.kg-1.day-1 of oral vitamin E were entered into a trial at eight centers in the United States. After initial evaluation, treatment was started with 25 IU.kg-1.day-1 of TPGS. Vitamin E status, neurological function quantitated by a specific scoring system, and clinical and biochemical parameters were monitored during therapy. RESULTS All children responded to TPGS with normalization of vitamin E status. Neurological function, which had deteriorated before entry in the trial, improved in 25 patients, stabilized in 27, and worsened in only 2 after a mean of 2.5 years of therapy. No adverse effects were observed. CONCLUSIONS TPGS (20-25 IU.kg-1.day-1) appears to be a safe and effective form of vitamin E for reversing or preventing vitamin E deficiency during chronic childhood cholestasis.

Pseudotumor Cerebri Associated with Initiation of Levothyroxine Therapy for Juvenile Hypothyroidism

Pseudotumor CEREBRI (benign intracranial hypertension), a syndrome characterized by increased intracranial pressure without focal neurologic dysfunction, occurs in association with a variety of end...

Dermatitis in treated maple syrup urine disease

Two children who had classic maple syrup urine disease developed an eruptive dermatitis when plasma isoleucine levels, leucine levels, or both fell below normal during periods of protein restriction. The dermatitis was resistant to topical corticosteroid therapy. Rapid resolution occurred after treatment with isoleucine and leucine dietary supplements.

Neurologic complications in galactosemia

Two siblings, a 27-year-old man and his 24-year-old sister were diagnosed with classic transferase deficiency galactosemia at birth and were treated with strict lactose restriction. Despite well-documented dietary management, both siblings are mentally retarded and manifest a progressive neurologic condition characterized by hypotonia, hyperreflexia, dysarthria, ataxia, and a postural and kinetic tremor. Magnetic resonance imaging revealed moderate cortical atrophy, a complete lack of normal myelination, and multifocal areas of increased signal in the periventricular white matter on T2-weighting. These patients suggest that even with early diagnosis and treatment, individuals with galactosemia may have significant neurologic morbidity with abnormalities of white matter development. This finding raises the possibility of biochemical heterogeneity within the classic transferase deficiency group, as well as the possibility of a lack of available galactose metabolites necessary for glycolipid synthesis causing a disruption of normal myelin development.

The noncerebrovascular complications of chiropractic manipulation.

We describe a patient who suffered cervical spine, spinal cord, and nerve root injury as a result of chiropractic spinal manipulation, and we review medical literature concerning the noncerebrovascular complications of spinal manipulation.

Variability of serial CT scans in subacute necrotizing encephalomyelopathy (Leigh disease).

Computed tomographic (CT) brain scans of patients with subacute necrotizing encephalomyelopathy (SNE) may reveal focal lesions that correspond to sites of anatomic involvement of the disease. Three patients with SNE were followed with serial CT brain scans. In two patients radiographic abnormalities appeared well after the onset of clinical symptoms. In all three patients the radiographic lesions changed with time. This variability seen with serial scanning is an important feature of SNE.

Overlooking: a Sign of Bilateral Central Scotomata in Children

Four children are reported who always looked above objects of visual interest (overlooking). All had bilateral central scotomata (loss of central visual field). Three had optic nerve disease selectively affecting the papillomacular fibers; the fourth had ocular colobomata affecting the maculae. Overlooking is an important sign of bilateral central scotomata in children: it is an adaptation to loss of central vision.

Posterior fossa hemorrhage in term newborns

Posterior fossa hemorrhage detected by computed tomography (CT) in seven term newborns was managed by nonsurgical means. All infants were developmentally normal two to four years later with the exception of one infant who died with a massive posterior fossa hemorrhage. Two infants with extensive hemorrhages developed hydrocephalus. Spinal fluid drainage and diuretic therapy resulted in the resolution of hydrocephalus in one infant and delayed the placement of a ventriculoperitoneal shunt in the other. This series documents normal outcome in nonsurgically managed neonatal posterior fossa hemorrhages of varying degrees of severity.

Phospholipid methylation in myogenic cells

The biosynthesis of phosphatidylcholine from successive N-methylation of phosphatidylethanolamine has been implicated as a major mechanism for the transduction of several receptor-mediated signals including beta-adrenergic coupling to adenylate cyclase. In this report we demonstrate L-isoproterenol stimulation of adenylate cyclase activity in two myogenic cell lines, L8 and BC3H-1. Using a sensitive high performance liquid chromatography method for qualitative and quantitative determination of phospholipids we found an active membrane phospholipid methylation pathway in these cells. Despite beta-adrenergic simulation of adenylate cyclase no alteration in the transmethylation pathway could be demonstrated.