Pyruvate carboxylase deficiency results in congenital lactic acidosis. We report the significant finding in a child with infantile spasms controlled with adrenocorticotrophin hormone (ACTH) but who then developed severe lactic acidosis; pyruvate carboxylase deficiency was subsequently diagnosed. Blood lactate, pyruvate, and alanine levels were elevated, as well as cerebrospinal fluid alanine. Plasma alanine concentration was doubled by ACTH therapy. Fibroblasts contained extremely low pyruvate carboxylase activity. The patient died at 12 weeks of age after recurrent episodes of profound acidosis. At autopsy, the brain manifested cystic degeneration and demyelination. Pyruvate carboxylase deficiency is associated with neonatal onset of acidosis, delayed development, seizures, hypotonia, recurrent profound acidosis, and early death. The dramatic rise in plasma alanine content coincident with ACTH therapy suggest that ACTH played a role in precipitating the catastrophic metabolic acidosis.

Acidosis, Lactic↗

PubMedDate not supplied

Structural features and regulatory properties of the brain glutamate decarboxylases.

It is widely recognized that the two major forms of GAD present in adult vertebrate brains are each composed of two major sequence domains that differ in size and degree of similarity. The amino-terminal domain is smaller and shows little sequence identity between the two forms. This domain is thought to mediate the subcellular targeting of the two GADs. Substantial parts of the amino-terminal domain appear to be exposed and flexible, as shown by proteolysis experiments and the locations of posttranslational modifications. The carboxyl-terminal sequence domain contains the catalytic site and shows substantial sequence similarity between the forms. The interaction of GAD with its cofactor, pyridoxal-5' phosphate (pyridoxal-P), plays a key role in the regulation of GAD activity. Although GAD(65) and GAD(67) interact differently with pyridoxal-P, their cofactor-binding sites contain the same set of nine putative cofactor-binding residues and have the same basic structural fold. Thus the cofactor-binding differences cannot be attributed to fundamental structural differences between the GADs but must result from subtle modifications of the basic cofactor-binding fold. The presence of another conserved motif suggests that the carboxyl-terminal domain is composed of two functional domains: the cofactor-binding domain and a small domain that closes when the substrate binds. Finally, GAD is a dimeric enzyme and conserved features of GADs superfamily of pyridoxal-P proteins indicate the dimer-forming interactions are mediated mainly by the carboxyl-terminal domain.

Animals↗

PubMedDate not supplied

Use of 5-nitroindole-2'-deoxyribose-5'-triphosphate for labelling and detection of oligonucleotides.

The 5'-triphosphate of 5-nitroindole-2'-deoxyriboside has been shown to be a good substrate for terminal deoxynucleotidyl transferase (TdT). An antibody has been prepared for the detection of 5-nitroindole and has been used for the detection of 5-nitroindole tailed DNA both in single-stranded form and after hybridisation to a template. This is therefore a new method for the detection of nucleic acid probes.

Antibodies↗

PubMedDate not supplied

Free amino acids in cerebrospinal fluid from patients with infantile spasms.

Profiles of free amino acids in cerebrospinal fluid (CSF) were determined by high-performance liquid chromatography for 20 nonneurologic control patients and 12 patients with infantile spasms. Statistical comparisons showed significantly elevated levels of lysine (p less than 0.001) and the excitatory neurotransmitter, glutamate, (p less than 0.01) for the infantile spasms group as compared to the nonneurologic control group. When the infantile spasms patients were subdivided according to the presence or absence of etiologic associations, highly elevated amino acid levels were observed only in CSF from patients of the symptomatic subgroup. The idiopathic subgroup showed levels of free amino acids that were not statistically different from those of the nonneurologic control group. These results indicate that while abnormalities of amino acid metabolism often accompany infantile spasms, no specific pattern of the major free amino acids in CSF appears to be directly related to this seizure disorder. Elevated levels of the excitatory amino acids, aspartate and glutamate, do not necessarily accompany infantile spasms, and in this study were only observed in symptomatic patients.

Adolescent↗

PubMedDate not supplied

Rate and volume of intermittent enteral feeding.

The purpose of this investigation was to determine the effects of the volume of enteral feedings and the rate at which they were administered on subject tolerance and gastric pressure changes. Fourteen normal volunteers received enteral feedings on 9 or 10 separate days. These feedings (Ensure) were administered in combinations of 3 volumes (250, 350, and 500 ml) and of 2 rates (30 and 85 ml/min). The effect on gastric motility was monitored by an open-tipped catheter. Nine of the subjects also received 750 ml administered at 30 ml/min. Six of the 14 subjects experienced nausea and/or discomfort during the first feeding trial (250 ml at 30 ml/min); however, subsequent feedings were tolerated without this discomfort. The rate at which feedings were administered had little effect on the time following feeding until the return of regular motility or on the mean motility index when 250 ml were administered; however, when larger volumes were administered at the faster rate, longer time was taken for the return of regular motility. Feedings administered at the faster rate were associated with a greater number of subjective complaints of abdominal discomfort, nausea, fullness, and cramping. The volume of a feeding has a significant effect on both the time required for regular motility to return following feeding and on the mean motility index, with the larger feeding volumes suppressing activity progressively longer. The volume of feeding (up to 750) ml) had little effect upon symptomatic tolerance of subjects when these feedings were administered at 30 ml/min. There was no significant interaction effect of rate and volume on the time required for motility to return following feedings. The results of this study indicate that normal subjects can tolerate bolus feedings of (250-750 ml) administered at 30 ml/min without distress. Additional studies are needed to compare bolus and continuous feedings in relation to patient tolerance, gastric emptying, and nutritional outcome.

Adult↗

PubMedDate not supplied

COACH conference probes future information systems.

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Canada↗

PubMedDate not supplied

Bloodless surgery: reducing risks of electrosurgery.

Explore the source record for details and available documents.

Electrosurgery↗