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I J Butler

Publications and source records attributed to I J Butler.

88 records · Page 5Linked to original sources
PubMed1978

A disorder of biogenic amines in dihydropteridine reductase deficiency.

A severe deficiency of dihydropteridine reductase (DHPR) in liver, brain, and cultured skin fibroblasts was demonstrated in a child with hyperphenylalaninemia and an atypical form of phenylketonuria. DHPR is required for regeneration of the cofactor, tetrahydrobiopterin. The cofactor is essential in hydroxylation of aromatic amino acid precursors in the biosynthesis of neurotransmitters, serotonin, dopamine, and norepinephrine. In gray tissue at brain biopsy, dopamine was low at 3 ng per gram of tissue, serotonin was barely detected, and norepinephrine appeared high at 1600 ng per gram. In cerebrospinal fluid, homovanillic acid (HVA) was low normal at 33 ng/ml, 5-hydroxyindoleacetic acid (5-HIAA) was low at 4.2 ng/ml, and after a high dose of oral probenecid there was impaired accumulation of HVA to 128 ng/ml and 5-HIAA to 22.4 ng/ml. When the patient was 22 months of age, treatment with hydroxylated aromatic amino acid precursors was initiated, and after three months HVA and 5-HIAA levels were increased in CSF. The apparent restoration of biogenic amines in brain appears to have delayed the rate of neurological deterioration. DHPR activity in cultured skin fibroblasts of children with persistent hyperphenylalaninemia should permit early diagnosis and early treatment of this disorder.

5-Hydroxytryptophan↗
PubMed1978

Gilles de la Tourette syndrome: further studies and thoughts.

A possible association between the Gilles de la Tourette and Lesch-Nyhan syndromes has recently been postulated. Fourteen patients with Tourette syndrome demonstrated no similarity to Lesch-Nyhan based upon patterns of inheritance, behavioral changes, or alterations of purine metabolism. Despite a strong male predominance, a sex-linked pattern of inheritance could not be confirmed. Self-mutilating behavior was found in 4 male patients but was readily differentiated from that characteristic of the Lesch-Nyhan syndrome. Quantitation of hypoxanthine-guanine phosphoribosyltransferase and isoelectric focusing of its isoenzymes produced results that were indistinguishable from those in controls. We speculate that, pathophysiologically, Tourette syndrome represents an imbalance between the central neurotransmitters dopamine and serotonin rather than an alteration in purine metabolism.

Child↗
PubMed1978

The effect of disuse on cholinergic enzymes.

1. The effects of disuse on the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) have been investigated in the sciatic nerve and leg muscles of the rat. 2. Disuse was produced by blockade of nerve conduction by repeated subperineurial injection of tetrodotoxin (TTX), and the effects were compared to those of denervation. 3. After 8 days of disuse there was no change in neural ChAT activity in the sciatic nerves, anterior roots or intramuscular terminals. By contrast, surgical section of the sciatic nerve resulted in a marked decrease of ChAT in the nerve terminals. 4. Similarly, after 8 days of disuse there was no change in neural AChE activity in the sciatic nerves or anterior roots. 5. AChE activity in the disused muscles decreased by more than 50%, which was comparable to the effect of surgical denervation. 6. These results indicate that disuse produced by TTX blockade of nerve conduction does not affect the cholinergic enzymes ChAT and AChE in nerves, but does lead to a significant decrease in muscle AChE.

Acetylcholinesterase↗
PubMed1977

Biogenic amine synthesis defect in dihydropteridine reductase deficiency.

In the enzymatic hydroxylation of aromatic amino acids, tetrahydrobiopterin is the essential cofactor. Regeneration of tetrahydrobiopterin requires dihydropteridine reductase, without which there should be a deficiency of hydroxylated amino acids and their products, biogenic amines. Assay of biopsied brain cortex of a patient with a deficiency of dihydropteridine reductases showed low concentrations of serotonin and dopamine, and this was reflected in the concentrations of their major metabolites measured in cerebrospinal fluid from lumbar, ventricular, and subarachnoid spaces. The metabolite concentrations were restored to normal, or above normal, by treatment with specific amino acids which bypass the metabolic block at the hydroxylation step. It is postulated that the seizures and neurological deterioration of the patient were related to a deficiency in the synthesis of biogenic amine neurotransmitters.

5-Hydroxytryptophan↗
PubMed1977

Chronic progressive poliomyelitis secondary to vaccination of an immunodeficient child.

We investigated an immunodeficient child in whom chronic progressive poliomyelitis developed after she had received live oral poliovirus vaccine. Poliovirus, Type II, was isolated from throat and stool during life and from several sites within the brain at autopsy. The brain isolate was classified as vaccine-like on the basis of temperature sensitivity and antigenic markers. However, in the monkey neurovirulence test, the brain isolate produced moderately severe lesions throughout the spinal cord and brainstem and appeared nonvaccine-like. Thus, the brain isolate demonstrated a dissociation between the antigenic and neurovirulence markers. Our observations suggest that, under unusual circumstances, such as immunodeficiency, attenuated poliovirus can produce a chronic progressive neurologic disease. This case also emphasizes the need to diagnose immunodeficiency as early as possible, so that live-virus vaccines will not be administered.

Agammaglobulinemia↗
PubMed1977

Long-term treatment of juvenile Huntington's chorea with dipropylacetic acid.

Since the proposed mode of action of dipropylacetic acid, an anticonvulsant, is to increase central nervous system gamma-aminobutyric acid levels, we used this agent to treat identical twins with juvenile Huntington's chorea. Their clinical status did not improve immediately after they received dipropylacetic acid. Furthermore, long-term administration (over a year) of high doses of the agent (up to 2,400 mg per day; 92 mg per kilogram per day) did not seem to alter the slow progression of their disease. Prior to treatment with dipropylacetic acid, the twins had normal cerebrospinal fluid gamma-aminobutyric acid levels. In addition, cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid were determined before and after 18 hours of high-dose probenecid. The former showed a normal threefold to fourfold increase after probenecid administration, but homovanillic acid had a distinctly subnormal turnover after probenecid, with only a threefold rather than the normal tenfold increase.

Child↗
PubMed1976

Kearns-Sayre syndrome. A review of a multisystem disorder of children and young adults.

The syndrome of a slowly progressive external ophthalmoplegia, pigment retinopathy, and disorder of cardiac conduction was described by Kearns and Sayre in 1958. In patients with this triad, other neurological deficits may occur with associated abnormalities of the electrocardiogram, electroencephalogram, audiogram, and an elevation of protein in cerebrospinal fluid. The onset of a potentially lethal cardiac dysrhythmia in a patient with this slowly progressive degeneration of the nervous system can be anticipated and prevented by the use of an artivicial cardiac pacemaker.

Adolescent↗
PubMed1976

Diencephalic syndrome revisited.

This report details the histories of five patients with clinical diencephalic syndrome who collectively demonstrate the variability found in the syndrome with respect to: (1) clinical course, (2) site of the tumor, and (3) ease of obtaining radiologic confirmation of the presence of a tumor. A review of an additional 67 patients indicates that the observations are not unique. The anatomic variability combined with the fact that the course of those who are treated is infinitely better than those left untreated adds urgency to the establishment of precise anatomic diagnosis. These considerations led to a critical review of the histories of the 72 patients. From this it can be stated that anteriorly and posteriorly placed tumors do exhibit subtle but significant differences in their clinical course, and roentgenograms of the optic foramina and analysis of the CSF cell and protein content appear warranted early in the investigation of emaciation from unknown cause. Further, an evaluation is made of the role of various radiologic techniques and of endocrine studies in establishing the diagnosis. Similarly, the relative merits of radiotherapy and/or surgery in the treatment of the disease are defined. Finally, the adequacy of the term diencephalic syndrome is discussed.

Astrocytoma↗
PubMed1976

Hyperphenylalaninemia due to dihydropteridine reductase deficiency. Assay of the enzyme in fibroblasts from affected infants, heterozygotes, and in normal amniotic fluid cells.

Two infant siblings with modest elevations of serum phenylalanine concentrations had seizures and developmental regression: they died in their second year. Dihydropteridine reductase activity, which can be measured in normal cultured skin fibroblasts, was measured in the younger sibling and was absent. Parents of the two siblings and parents of a previously reported patient all showed 50% or less of the normal dihydropteridine reductase activity in their cultured fibroblasts. Dihydropteridine reductase activity is also present in normal cultured amniotic fluid cells, offering the possibility of prenatal diagnosis. Absence of dihydropteridine reductase results not only in a defect in the conversion of phenylalaning to tyrosine, but also in the biosynthesis of the neurotransmitters, dopamine, norephinephrine, and serotonin. Since deficiencies in these neurotransmitters would not be alleviated by a phenylalanine-restricted diet, it is important to establish the nature of the enzymatic defect in all suspected variants of phenylketonuria.

Adult↗
PubMed1975

Bone marrow in the Batten-Vogt syndrome.

Six children with clinical and pathological features of Batten-Vogt syndrome showed autofluorescent material in bone marrow cells and in 5 of them sea-blue histiocytes were seen. It is suggested that bone marrow examination for sea-blue histiocytes and autofluorescenceis a useful screening test for ceroid-lipofuscinosis.

Bone Marrow↗
PubMed1975

Combined immunodeficiency and vaccine-related poliomyelitis in a child with cartilage-hair hypoplasia.

Patients previously described with cartilage-hair hypoplasia, a distinctive form of short-limbed dwarfism, have been found to have deficient cell-mediated immunity with intact antibody-mediated immunity. The patient with cartilage-hair hypoplasia described in the present report is unusual in that she had both deficient antibody-mediated immunity and deficient cell-mediated immunity. In addition, she developed severe, vaccine-related paralytic poliomyelitis. This complication suggests that live viral vaccines should not be administered to children with short-limbed dwarfism until the form of short-limbed dwarfism is established and immunologic evaluation is performed when indicated.

Bone and Bones↗
PubMedDate not supplied

In vivo muscle magnetic resonance spectroscopy in a family with mitochondrial cytopathy: a defect in fat metabolism.

In vivo proton and phosphorus magnetic resonance spectroscopy (MRS) studies were performed at 1.5 T on two patients (siblings) diagnosed as having a mitochondrial cytopathy. The clinical diagnosis was based on a complete battery of biochemical tests, electron microscopy and modified Gomori trichrome stain studies of muscle. Proton spectra from the gastrocnemius muscle were recorded using the stimulated echo acquisition mode (STEAM) and the phosphorus spectra were obtained using the depth-resolved surface coil spectroscopy (DRESS) sequence. Proton resonances from neutral fats in the patients were found to be strikingly weak compared to normals. The ratios [PCr]/[ATP] and [PCr]/[Pi] and the pH values, as inferred from the phosphorus MRS, were found to be marginally decreased compared to normals. These studies indicate defective fatty acid metabolism in these two patients. It is, however, not known whether the abnormal mitochondrial ultrastructure represents a primary abnormality or secondary to defective fatty acid metabolism.

Adult↗
PubMedDate not supplied

Amoxapine overdose in a young man: a transient mitochondrial abnormality?

Amoxapine is a second-generation tricyclic antidepressant structurally related to the neuroleptic loxapine. It was previously marketed as an alternative to traditional tricyclic antidepressants because of alleged shorter onset of action and fewer cardiotoxic effects. However, various adverse reactions, including cardiac dysrhythmias, renal failure, coma, seizures, and neuroleptic malignant syndrome, were reported during therapy or after acute overdose. A 14-year-old boy ingested 1900 mg of amoxapine and developed seizures, hypertension, hyperpyrexia, altered mental status, myoglobinuria, renal failure, and transient magnetic resonance imaging (MRI) changes suggestive of hypertensive encephalopathy and neuroleptic malignant syndrome. Since mitochondrial disorders can cause multisystem failure, including encephalopathy, renal tubular dysfunction, and myopathy, a transient, toxic disorder of mitochondrial function was considered as the basis for the patient's clinical and MRI changes.

Adolescent↗