Acute profound dystonia in infants with glutaric acidemia.

Acute profound dystonia developed in three previously well infants who were found to have glutaryl-CoA dehydrogenase deficiency in cultured skin fibroblasts. Two patients had excessive urinary excretion of glutaric acid, but one did not. Neuroradiologic studies performed in all three patients at the onset of their illnesses revealed large CSF-containing spaces both within the sylvian fissures and anterior to the temporal lobes.

Cerebral metabolic response and mitochondrial activity following insulin-induced hypoglycemia in newborn lambs.

We evaluated the newborn lamb's cerebral cellular activity and metabolism following acute insulin-induced hypoglycemia. Eleven animals received an insulin bolus followed by a continuous infusion to maintain a plasma glucose of 1 mM/l for 2 h, while 8 other animals received an equivalent dose of saline. Following the induction of hypoglycemia, the animals became quiet and transient seizures were observed in 3 animals.

Medium-chain acyl-CoA dehydrogenase deficiency: metabolic effects and therapeutic efficacy of long-term L-carnitine supplementation.

Medium-chain acyl-CoA dehydrogenase deficiency is a recently described inborn error of metabolism characterized by episodes of coma and hypoketotic hypoglycaemia in response to prolonged fasting. Secondary carnitine deficiency has been documented in these patients as well as the excretion in the urine of medium-chain-length acyl carnitine esters, such as octanoylcarnitine. Based on the potential toxicity of medium-chain fatty acid metabolites and the beneficial responses of patients with other inborn errors of metabolism and secondary carnitine deficiency, oral carnitine has been proposed as treatment for children with medium-chain acyl-CoA dehydrogenase deficiency.

Medium-chain acyl-CoA dehydrogenase deficiency. Diagnosis by stable-isotope dilution measurement of urinary n-hexanoylglycine and 3-phenylpropionylglycine.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, one of the most common inherited metabolic disorders, is often mistaken for the sudden infant death syndrome or Reye's syndrome. Diagnosing it has been difficult because of a lack of fast and reliable diagnostic methods. We developed a stable-isotope dilution method to measure urinary n-hexanoylglycine, 3-phenylpropionylglycine, and suberylglycine, and we retrospectively tested its accuracy in diagnosing MCAD deficiency.

Amperometric enzyme-amplified immunoassays.

Enzyme-amplified immunoassays have been adapted for electrochemical measurement, using an NAD+/NADH redox cycle coupled to an electrode via the active site of diaphorase. Two amperometric methods are described, the first employs an organic conducting salt electrode, NMP+/TCNQ-; the second a platinum wire with ferricyanide as electron transfer mediator. In an immunoenzymometric assay for human prostatic acid phosphatase the sensitivities of the electrochemical methods were comparable to that achieved with the existing optical technique, but the dynamic range of the electrochemical assays was increased by at least two orders of magnitude.

Relationship between unusual hepatic acyl coenzyme A profiles and the pathogenesis of Reye syndrome.

This study examines the relationship between impaired fatty acid oxidation and the pathogenesis of Reye syndrome. We present a hypothesis proposing that many clinical signs of this childhood disease are caused by accumulation of unusual acyl CoA esters, precursors to deacylated metabolites found in the patients' blood and urine. A new method was developed to measure acyl CoA compounds in small human liver biopsy samples, offering several advantages over previous techniques.

Mixed hearing loss in Larsen syndrome.

A mixed bilateral hearing loss is described in a child with classical Larsen syndrome. The presence of a residual conductive loss after successful placement of ventilating tubes suggests that the conductive loss is due to an ossicular abnormality. In Larsen syndrome, characterized by multiple joint dislocations and bony malformations, the ossicular joints may also be affected.

An inhibition enzyme immunoassay for estimating relative antibody affinity and affinity heterogeneity.

A method to measure the relative affinity of antibodies using an inhibition enzyme immunoassay is described. It is validated using monoclonal antibodies of defined affinity characteristics and by comparison with conventional methods of affinity measurement. The method allows measurement of the relative affinity of low levels of antibody, and the calculation of an empirical estimate of the heterogeneity of affinity in antibody populations.

Immunity to hepatitis B: analysis of antibody and cellular responses in recipients of a plasma-derived vaccine using synthetic peptides mimicking S and pre-S regions.

The potential of a panel of synthetic HBsAg peptides as components of a synthetic hepatitis B vaccine was assessed. Each was used in turn as probes to analyse human immune responses to a licensed plasma-derived HBV vaccine. Both humoral and cellular responses were analysed with synthetic peptides representing residues 124-147 of the surface antigen of the virus (HBsAg) and residues 126-140 of the pre-S2 region.

Enzyme-amplified immunoassays.

The sensitivity of enzyme immunoassays may be enhanced by the use of enzyme-amplification. This technique uses the enzyme label in the immunoassay to provide a trigger substance for a secondary system that can generate a large quantity of coloured product. Two examples of enzyme amplifiers are described, using either a substrate cycle with phosphorylated hexose sugars, or a redox cycle involving the coenzyme NAD(+).

New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency.

There are now nine inherited diseases that have been identified in the pathway of mitochondrial fatty acid oxidation, including LCAD, MCAD, SCAD, and HMG-CoA lyase deficiencies, two forms each of CPT and MAD deficiencies and an incompletely characterized disorder of primary carnitine deficiency. The varied range of clinical manifestations in this new group of diseases should attract the attention not only of general pediatricians (coma, hypoglycemia) but also of pediatric subspecialists in neurology (myopathy), cardiology (cardiomyopathy), and gastroenterology (fatty liver), as well as genetics and metabolism. The presenting features of the genetic defects in fatty acid oxidation fit well with the concept that fatty acid oxidation plays a major role in energy production during prolonged fasting and in working cardiac and skeletal muscle.

Medium-chain and long-chain acyl CoA dehydrogenase deficiency: clinical, pathologic and ultrastructural differentiation from Reye's syndrome.

The clinical and pathologic findings in 12 patients with medium-chain acyl CoA dehydrogenase deficiency and three patients with long-chain acyl CoA dehydrogenase deficiency are summarized. Although these inborn errors of intramitochondrial beta-oxidation of fatty acids present with similar findings to Reye's syndrome, there are clinical, laboratory and hepatic histologic differences. Younger age at presentation, history of unexplained sibling death, a previous episode of lethargy, hypoglycemia or acidosis precipitated by fasting stress and only mildly elevated serum transaminases with normal or only mildly prolonged prothrombin time may all suggest an acyl CoA dehydrogenase deficiency.

Mechanisms of transfer of steroid hormones and growth factors into milk.

In this paper we examine the ability of the mammary gland to remove from circulating blood three compounds which differ in their physico-chemical and structural properties. Mammary extraction of progesterone, oestrone sulphate and epidermal growth factor (EGF) is similar at peak lactation in goats, but the proportion of labelled infusate that is transferred into milk is greater for oestrone sulphate and EGF than progesterone which is rapidly metabolised by mammary tissue. The kinetics of transfer of progesterone, oestrone sulphate and EGF from blood into milk show that transcellular processes are involved, and on the basis of earlier hypotheses and new information reported here the results indicate the probable importance of simple and facilitated diffusion pathways for progesterone and oestrone sulphate, and secretory mechanisms for oestrone sulphate and EGF.

Neonatal neurosonographic correlates of cerebral palsy in preterm infants.

Serial neurosonographic examinations are routinely performed at frequent intervals during the nursery course of all preterm infants of 33 weeks or less gestation who are admitted to the intensive care nursery of Thomas Jefferson University Hospital. After discharge, the following survivors during the past 5 years had repeated ultrasound examinations until the anterior fontanel closed and clinical assessments until the presence or absence of cerebral palsy at a minimum age of 12 months was established: all infants with grade III/IV intracranial hemorrhage, periventricular echodensity and periventricular cyst formation, selected infants with either normal ultrasound findings or grade I/II intracranial hemorrhage. Fifteen survivors were found to have cerebral palsy, and all had at least one of the following ultrasound abnormalities: diffuse, bilateral, and multiple periventricular cysts 3 mm or more in diameter that persisted beyond term age, bilateral asymmetrical dilation of the lateral ventricles following grade III intracranial hemorrhage with small periventricular cysts, and ventricular porencephaly following an ipsilateral grade IV intracranial hemorrhage.

Use of a new and rapid milk progesterone assay to monitor reproductive activity in the cow.

A new and rapid enzyme-amplified immunoassay (AELIA) has been developed for the measurement of progesterone in milk. The AELIA system is a non-isotopic method that gives results within 35 minutes. Milk progesterone concentrations measured in 10 cows sampled daily at various stages of the reproductive cycle were very similar to those recorded by a validated radioimmunoassay.

Late effects after treatment of twenty children with soft tissue sarcomas of the head and neck. Experience at a single institution with a review of the literature.

Twenty children with soft tissue sarcomas of the head and neck, treated at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania from 1972 to 1981, were evaluated for the late deleterious effects of treatment. All patients received radiation therapy and combination chemotherapy with vincristine, dactinomycin, and cyclophosphamide; certain patients also received Adriamycin (doxorubicin). All had ophthalmologic, otologic, growth, and cosmetic evaluations; 15 also had dental and maxillofacial examinations.

Impaired chemotaxis and neutrophil (polymorphonuclear leukocyte) function in glycogenosis type IB.

Polymorphonuclear leukocyte (PMN) function was investigated in two patients with glycogen storage disease type IB and neutropenia. Glycogen storage disease type IB was documented by liver biopsy and a normal amount of latent glucose-6-phosphatase activity. Patient A had stomatitis, skin infections, and septicemia; patient B had respiratory infections, periodontitis, and oral candidiasis.

Pulmonary balloon valvoplasty in late adult life.

A case of severe valvar pulmonary stenosis in a 60-year-old woman is described. Percutaneous balloon valvoplasty was performed without complication and reduced the right ventricular outflow pressure gradient from 95 mm Hg to 25 mm Hg. Balloon valvoplasty is an effective alternative to surgical valvotomy in adults as well as children.