PubMed Health⌕ Search

Biomedical subjects

I J Butler

Publications and source records attributed to I J Butler.

At least 55 records · Page 3Linked to original sources
PubMed1989

Circumvention of defective neutral amino acid transport in Hartnup disease using tryptophan ethyl ester.

Tryptophan ethyl ester, a lipid-soluble tryptophan derivative, was used to bypass defective gastrointestinal neutral amino acid transport in a child with Hartnup disease. The child's baseline tryptophan concentrations in serum (20 +/- 6 microM) and cerebrospinal fluid (1.0 +/- 0.2 microM) were persistently less than 50% of normal values. Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite, was also less than 50% of normal (21 +/- 2 ng/ml). Serum tryptophan concentrations increased only modestly and briefly after an oral challenge with 200 mg/kg of oral L-tryptophan, reflecting the absorptive defect. An oral challenge with 200 mg/kg of tryptophan ethyl ester resulted in a prompt increase in serum tryptophan to a peak of 555 microM. Sustained treatment with 20 mg/kg q6h resulted in normalization of serum (66 +/- 15 microM) and cerebrospinal fluid tryptophan concentrations (mean = 2.3 microM). Cerebrospinal fluid 5-HIAA increased to more normal concentrations (mean = 33 ng/ml). No toxicity was observed over an 8-mo period of treatment, chronic diarrhea resolved, and body weight, which had remained unchanged for 7 mo before ester therapy, increased by approximately 26%. We concluded that tryptophan ethyl ester is effective at circumventing defective gastrointestinal neutral amino acid transport and may be useful in the treatment of Hartnup disease.

Amino Acids↗
PubMed1988

Lesch-Nyhan syndrome: a study of motor behavior and cerebrospinal fluid neurotransmitters.

We studied 5 boys, 2 to 10 years old, with marked or complete deficiency of hypoxanthine-guanine phosphoribosyltransferase and Lesch-Nyhan syndrome with varying degrees of mental retardation, dysarthria, chorea, dystonia, spasticity, and ataxia. Four patients had marked reduction of homovanillic acid in the cerebrospinal fluid (CSF) and all showed low CSF 3-methoxy-4-hydroxy phenylethylene glycol, indicating reduced dopamine and norepinephrine turnover. Three patients showed high CSF 5-hydroxyindoleacetic acid, suggesting increased serotonin turnover. Some patients improved with carbidopa-levodopa, but others benefited from tetrabenazine, a monoamine-depleting agent. This study provides support for the theory of abnormal central monoamine metabolism in Lesch-Nyhan syndrome.

Carbidopa↗
PubMed1988

Neurological basis of respiratory complications in achondroplasia.

Evaluation of 32 individuals with achondroplasia revealed that 28% had a history of apnea and 22% had respiratory abnormalities on polysomnography. In those patients requiring posterior fossa decompressive surgery, improvement was noted in follow-up polysomnograms. Multimodality studies suggested that brainstem compression was common in achondroplasia and could account in part for the abnormal respiratory function in this disorder, including obstructive apnea, central apnea, and hypoxemia.

Achondroplasia↗
PubMed1988

Transverse sinus thrombosis in newborns: clinical and magnetic resonance imaging findings.

Neonatal transverse sinus thrombosis (TST) is considered a rare and severe sequela of birth injury. Clinical descriptions of this entity are few since most published series are postmortem studies. The advent of magnetic resonance imaging (MRI) allows recognition of TST ante mortem. We describe 4 full-term infants with distinct clinical and neuroradiological features indicative of TST, which we suggest may be relatively common, with a wide spectrum of severity, including favorable outcome.

Brain↗
PubMed1987

Folinic acid therapy in treatment of dihydropteridine reductase deficiency.

We gave folinic acid to three siblings, and to a fourth child, who have or had dihydropteridine reductase (DHPR) deficiency. The youngest began folinic acid therapy in addition to neurotransmitter precursors and a phenylalanine-restricted diet at age 2 months, and at 2 years of age has near normal development without evidence of neurologic impairment. His older brother began similar treatment at 5 1/2 months of age, when early neurologic findings were evident. At age 6 years his mental retardation and neurologic impairment are less severe than reported in most patients with DHPR deficiency. Little improvement occurred in their sister, who first received treatment at 2 years of age, when she already had severe neurologic impairment. An unrelated boy with profound neurologic impairment showed subtle signs of improvement after he began treatment with folinic acid alone at age 9 years. These results provide evidence that folinic acid is important in the treatment of DHPR deficiency and, if begun early in infancy, may prevent irreversible neurologic damage. The mechanism of folinic acid action in DHPR deficiency may be to increase indirectly the synthesis of 5-methyltetrahydrofolate.

5-Hydroxytryptophan↗
PubMed1987

Dietary folate and biogenic amines in the CNS.

Abnormal biogenic amine biosynthesis has been observed in humans and animals with endogenous and exogenous disturbances in folate metabolism. In an attempt to study this interaction biochemically, rats were depleted or repleted with folate for 10 weeks. Folate levels in depleted animals in serum and CSF correlated with stores in liver and brain, respectively. In depleted or repleted animals, there was no significant effect on biogenic amine metabolism in the CNS, as determined by quantitation of biogenic amines in brain and their respective metabolites in brain and CSF. These results are contrary to studies by other investigators. We suspect, however, that specific genetic defects in folate metabolism do result in impaired biogenic amine metabolism and probably at the level of disturbed biopterin cofactor functions.

Animals↗
PubMed1987

Myelopathy in neonatal and infantile lupus erythematosus.

Two children with lupus erythematosus and myelopathy were studied. The first child developed the neonatal lupus erythematosus syndrome associated with transplacentally acquired anti-Ro/SSA antibodies. The cutaneous manifestations of neonatal lupus erythematosus disappeared but a residual myelopathy was confirmed at 16 months of age. The second child developed cutaneous lupus erythematosus at 3 months of age associated with a total deficiency of the Clr component of complement. A myelopathy and mesangial glomerulonephritis developed at 2 years of age which required treatment with corticosteroids. These two children with CNS lupus erythematosus, one associated with transplacentally acquired antibodies and the other associated with a complement deficiency, may suggest an immune-mediated mechanism for the pathogenesis of myelopathy in childhood lupus erythematosus.

Antibodies, Antinuclear↗
PubMed1987

Infantile herpes zoster ophthalmicus and acute hemiparesis following intrauterine chickenpox.

A 17-month-old boy developed herpes zoster ophthalmicus (HZO) and delayed contralateral hemiparesis following intrauterine varicella exposure. CT demonstrated multiple areas of hypodensity in the left basal ganglia, and angiography showed occlusion of left lenticulostriate arteries. As in most adults with HZO and delayed hemiparesis, this infant had a self-limiting course with excellent recovery.

Acyclovir↗
PubMed1986

Foramen magnum stenosis in homozygous achondroplasia.

A 4-month-old female with homozygous achondroplasia and daytime apnea was found to have a small foramen magnum by computerized tomography. Following suboccipital craniectomy and C1-C2 laminectomy respiratory problems did not recur during a 7 month post-operative period. We suggest that the respiratory problems in homozygous achondroplasia may be due to brainstem compression from an abnormally small foramen magnum.

Achondroplasia↗
PubMed1986

Familial lethal cardiomyopathy with mental retardation and scapuloperoneal muscular dystrophy.

A family is described with a neuromuscular disorder characterised by possible X-linked recessive inheritance, a benign, slowly progressive muscular dystrophy with predominant humeroperoneal distribution and lack of contractures or pseudohypertrophy, central nervous system involvement, myopia and lethal cardiomyopathy. The possibility of cardiac transplant as life-saving therapy is suggested.

Adolescent↗
PubMed1986

Glutamyl ribose-5-phosphate storage disease: nephrotic syndrome and cerebral atrophy.

Storage of glutamyl ribose-5-phosphate was identified at autopsy in the brain and kidney of an 8-year-old male who had presented clinically with progressive renal failure and neurological deterioration. In a renal biopsy during life, glomeruli were focally sclerotic and contained foam cells. By electron microscopy, lysosomal accumulation was present in renal tubular and glomerular epithelial cells, hepatic Kupffer cells, and conjunctival connective tissue cells. Ganglion cells in the brain stem had swollen, PAS-positive cytoplasm with central chromatolysis. The cerebral cortex was atrophic and there was loss of Purkinje cells in the cerebellum. The identification of storage was based on biochemical isolation of the compound from the tissues at autopsy. The enzyme deficiency responsible for the storage has not yet been identified.

Atrophy↗
PubMed1985

Reduction of biogenic amine levels in the Rett syndrome.

The Rett syndrome is a progressive disorder in female patients that is characterized by autistic behavior, dementia, ataxia, loss of purposeful use of the hands, and seizures. The results of laboratory investigations are usually normal, with the exception of electroencephalography. In an attempt to understand the pathogenesis of this syndrome, we assayed biogenic amine metabolites in the cerebrospinal fluid of six patients, 2 to 15 years of age. 3-Methoxy-4-hydroxyphenylethylene glycol (MHPG, a metabolite of norepinephrine), homovanillic acid (a metabolite of dopamine), and 5-hydroxyindoleacetic acid (5-HIAA, a metabolite of serotonin) were quantitated by a method involving gas chromatography and mass spectrometry. Levels of MHPG and homovanillic acid were significantly reduced in all the patients as compared with those in controls of similar age (P = 0.01 and 0.008, respectively). The reduction in the level of 5-HIAA was not significantly different from that in the controls (P = 0.15). These findings suggest an underlying disorder of biogenic amines in the Rett syndrome and may provide new insight into its pathogenesis.

Adolescent↗
PubMed1985

Computerized tomography of the foramen magnum: achondroplastic values compared to normal standards.

Computerized tomographic dimensions of the foramen magnum of 63 achondroplastic individuals were compared to standards established for nonachondroplastic individuals. The size of the foramen magnum in patients with achondroplasia was small at all ages, particularly in those with serious neurologic problems. The data suggest that measurement of the foramen magnum may identify achondroplastic individuals at high risk of developing neurologic complications.

Achondroplasia↗
PubMed1985

Prenatal and postnatal hypothyroidism abolishes lesion-induced noradrenergic sprouting in the adult rat.

The effects of altered thyroid states on regeneration in the central nervous system are equivocal. This work was undertaken to examine the influence of propylthiouracil-induced (PTU-induced) pre- and postnatal hypothyroidism on collateral sprouting of noradrenergic (NA) axons in the habenula (Hb), following lesions in the stria medullaris (SM) of the adult rat. Ten pregnant dams were divided into control and PTU-treated groups. Control rats had free access to food and water and the hypothyroid group received, in addition, 0.05% (w/v) of PTU in their drinking water, beginning on day 12 of gestation and continuing post partum through lactation until the offspring were weaned at age 22 days. The pregnant dams received, in addition, daily injections of thyroxine (25 micrograms/kg, ip) and only male pups were used in the study. At weaning the pups were removed from the dams and placed in cages with free access to food and water. The hypothyroid offspring received 0.05% (w/v) PTU in the drinking water until sacrificed at 10 weeks of age. At 6 weeks, some rats in each group received bilateral lesions in the SM and the remainder were sham-operated. All rats were sacrificed 4 weeks after operation. Thus, four groups were formed: 1) control/sham, 2) control/lesion, 3) PTU/sham, 4) PTU/lesion. Sprouting of NA fibers in discrete regions of the Hb was identified by norepinephrine (NE) levels and by fluorescence histochemistry. Blood levels of thyroid stimulating hormone (TSH) were determined. The results show that pre- and postnatal induced chronic hypothyroidism abolished NA sprouting in the partially deafferented Hb. Furthermore, lesions of the SM resulted in a marked decrease in serum TSH levels.

Adrenergic Fibers↗
PubMed1985

Congenital hypomyelinating neuropathy.

Two patients with congenital hypomyelinating neuropathy are reported with details of sural nerve pathology. The resemblance of this condition to the hypomyelinating neuropathy of Trembler mice is discussed and the pertinent medical literature reviewed.

Axons↗
PubMed1984

Progressive neurologic deterioration and renal failure due to storage of glutamyl ribose-5-phosphate.

A six-year-old boy presented with a history of seizures, progressive neurologic deterioration, and proteinuria. Physical examination revealed mildly coarse facies, failure to thrive, generalized hypotonia with muscle wasting, and optic atrophy; there was no organomegaly. The family history suggested an X-linked recessive inheritance. The electroencephalogram, electroretinogram, evoked potentials, and computed axial tomography of the brain were abnormal. Urine oligosaccharide chromatography, urine amino acids and organic acids, and results of leukocyte and fibroblast lysosomal-enzyme assays for the known storage diseases were normal; however, conjunctival and renal biopsy specimens contained enlarged lysosomes on electron microscopy. The patient had progressive neurologic deterioration and died of renal failure at eight years of age. A compound identified as glutamyl ribose-5-phosphate was purified from the brain (0.96 mumol per gram, wet weight) and kidney (0.60 mumol per gram, wet weight). This compound is the linkage group in ADP-ribosylation of proteins, an important regulatory process in gene expression and DNA repair. We believe this new disorder represents a glycoproteinosis that results in the cytoplasmic storage of glutamyl ribose-5-phosphate.

Brain↗