Biomedical subjects
L Baker
Publications and source records attributed to L Baker.
Hyperglycemia-induced teratogenesis is mediated by a functional deficiency of arachidonic acid.
Congenital malformations now represent the largest single cause of mortality in the infant of the diabetic mother. The mechanism by which diabetes exerts its teratogenic effects is not known. This study evaluated whether arachidonic acid might be involved, a possibility raised by the role of arachidonic acid in palatal elevation and fusion, processes analogous to neural tube folding and fusion. This hypothesis was tested in two animal models of diabetic embryopathy, the in vivo pregnant diabetic rat and the in vitro hyperglycemic mouse embryo culture. The subcutaneous injection of arachidonic acid (200-400 mg/kg per day) into pregnant diabetic rats during the period of organ differentiation (days 6-12) did not alter the maternal glucose concentration, the maternal weight gain, or the weight of the embryos. However, the incidence of neural tube fusion defects was reduced from 11% to 3.8% (P less than 0.005), the frequency of cleft palate was reduced from 11% to 4% (P less than 0.005), and the incidence of micrognathia was reduced from 7% to 0.8% (P less than 0.001). The addition of arachidonic acid to B10.A mouse embryos in culture also resulted in a reversal of hyperglycemia-induced teratogenesis. The teratogenic effect of D-glucose (8 mg/ml) in the medium resulted in normal neural tube fusion in only 32% of the embryos (P less than 0.006 when compared to controls). Arachidonic acid supplementation (1 or 10 micrograms/ml) produced a rate of neural tube fusion (67%) that was not significantly different from that observed in controls. The evidence presented indicates that arachidonic acid supplementation exerts a significant protective effect against the teratogenic action of hyperglycemia in both in vivo (rat) and in vitro (mouse) animal models. These data therefore suggest that the mechanism mediating the teratogenic effect of an increased glucose concentration involves a functional deficiency of arachidonic acid at a critical stage of organogenesis.
Stimulated mitotic counts in the non-lesional skin of patients with psoriasis and controls.
Mitotic counts have been determined in the symptomless skin of nine psoriatic patients and nine healthy controls 48 h after pressure-tape stripping. A significantly increased response was seen in the symptomless psoriatic epidermis compared with the controls.
Decreased synthesis of interleukin-2 (IL-2) in insulin-dependent diabetes mellitus.
Synthesis of interleukin-2 (IL-2) by lymphocytes from 26 insulin-dependent diabetic subjects (IDDM) was compared with that by lymphocytes from 24 nondiabetic control subjects. The control group produced 1.001 +/- 0.071 U/ml (mean +/- SEM). The IDDM group, containing patients diagnosed between 5 days and 10 yr before testing, produced only 0.59 +/- 0.050 U/ml (P less than 0.002). IL-2 synthesis by 6 non-insulin-dependent diabetic subjects (NIDDM) was not decreased (mean +/- SEM, 1.20 +/- 0.04 U/ml). Moreover, decreased levels of IL-2 production was found with lymphocytes of patients in good control, as well as those in poor control. These data suggest that decreased IL-2 synthesis is specific for IDDM, not explainable solely as a consequence of poor metabolic control, and thus, might be involved in the pathogenesis of the disease.
Parental mental illness and psychiatric disorders in "at risk" children.
Data are reported from psychiatric evaluations of a large group of communication disordered children and their parents who presented to a community speech clinic. Systematic psychiatric evaluations involving the use of standardized interviews, questionnaires, and DSM-III diagnostic criteria reveal that approximately 50% of the children have definable DSM-III psychiatric disorders and approximately the same percentage of children have at least one psychiatrically ill parent. Comparisons of children with psychiatrically ill parents and children with psychiatrically well parents show that parental psychiatric disorder is associated with increased psychopathology in the children. However, other factors, particularly psychosocial stress, are more strongly correlated with the presence of childhood psychopathology. There are few correlations between the types of parental psychiatric disorders and the types of childhood disorders.
Glycogen storage disease: effects of glucose infusions on [15N]glycine kinetics and nitrogen metabolism.
The effects of intragastric glucose infusions on [15N]glycine kinetics and whole body protein turnover were investigated in four children with type I and two children with type III glycogen storage disease. Either fasting or the administration of insufficient glucose was associated with a diminution in the glycine pool size relative to values observed when patients received adequate glucose. The cause of the smaller pool size was an increased fractional glycine turnover. Simultaneous determination of whole body protein turnover, using a stochastic model based on [15N]urea excretion, showed higher rates of protein synthesis, nitrogen flux, net tissue protein retention, and reutilization of amino acid nitrogen derived from protein catabolism, in patients receiving sufficient exogenous glucose. Depletion of amino acid pools, presumably because of intensive utilization of these gluconeogenic precursors when inadequate glucose is administered, was associated with a lower rate of whole body protein synthesis.
High-dose methotrexate with leucovorin rescue plus vincristine in advanced sarcoma: a Southwest Oncology Group study.
Twenty-six evaluable patients with advanced soft tissue and bony sarcomas refractory to chemotherapy were treated with vincristine plus high-dose methotrexate and leucovorin rescue. A 14% response rate was observed among 14 patients presenting with refractory soft tissue sarcomas. No responses were observed among 12 patients with bony sarcoma. Toxic reaction with nausea, vomiting, nephrotoxicity, and myelosuppression was manageable. While this study did demonstrate activity of this regimen in doxorubicin-refractory patients, the duration of the responses was relatively brief. Thus, the clinical utility of such a regimen is questionable.
Vasculitis, pulmonary cavitation, and anemia during antithyroid drug therapy.
Two thyrotoxic girls, aged 12 and 16 years, had a clinical picture consisting of purpuric skin rash, nephritis, pulmonary cavitation, hemoptysis, and profound anemia during antithyroid drug therapy. These major toxic manifestations prompted discontinuation of antithyroid drugs and institution of antibiotic and glucocorticoid therapy before the resolution of the severe illness. The girls eventually required ablative doses of radioactive iodine, and one of them had a thyroidectomy for the treatment of thyrotoxicosis. The skin biopsy specimen in one patient was indicative of mononuclear cell cutaneous vasculitis. After recovery, the patients had no evidence Of persistent anemia, nephritis, or pulmonary parenchymal disease.
Reactivity to alcohol cues in alcoholics and non-alcoholics: implications for a stimulus control analysis of drinking.
The present study is an attempt to identify responses to alcohol-related stimuli which might differentiate alcoholics from non-alcoholics. The assumption was that alcoholics would be more reactive to alcohol cues because of prior conditioning history with respect to alcohol and drinking. Eight alcoholics in treatment were compared with ten non-alcoholic controls and two recovering alcoholics, using swallowing and salivation as the principal dependent measures. (The concordance of swallowing and salivation was validated using dental rolls with an independent group of ten alcoholics.) Five-minute "sniff-trials" were provided in which subjects smelled either cedar chips or their favorite alcoholic beverage, in a labelled container. Swallowing (salivation) and craving (desire to drink alcohol) were significantly elevated in alcohol-sniffing trials for alcoholics in treatment compared with non-alcoholics; cardiac rate and galvanic skin response duration were also elevated in alcoholics in treatment, though not significantly. Recovering alcoholics resembled alcoholics in treatment more closely than they resembled non-alcoholics. The data were examined in the context of conditioned withdrawal resembled non-alcoholics. The data were examined in the context of conditioned withdrawal and homeostatic protective mechanisms. Implications for the stimulus control analysis of drinking were discussed.
The effect of early feeding on plasma glucose levels in SGA infants.
Plasma glucose levels were measured during the first day of life in 24 small-for-gestational-age (SGA) infants who began formula feedings within two hours of birth. In contrast to the high incidence of low blood sugar seen previously in fasted SGA infants, no infant had a plasma glucose below 30 mg/dl; after the first feeding, no values below 40 mg/dl occurred. Mean plasma glucose levels were lower in infants born to mothers with preeclampsia (57.2 +/- 2 vs 69.7 +/- 2.3 mg/dl, p less than .005). The results indicate that hypoglycemia (plasma glucose less than 40 mg/dl) can be easily avoided in SGA infants simply by providing adequate calories without delay after delivery.
Development of hepatic fatty acid oxidation and ketogenesis in the newborn guinea pig.
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Medium-chain acyl-CoA dehydrogenase deficiency in children with non-ketotic hypoglycemia and low carnitine levels.
Three children in two families presented in early childhood with episodes of illness associated with fasting which resembled Reye's syndrome: coma, hypoglycemia, hyperammonemia, and fatty liver. One child died with cerebral edema during an episode. Clinical studies revealed an absence of ketosis on fasting (plasma beta-hydroxybutyrate less than 0.4 mmole/liter) despite elevated levels of free fatty acids (2.6-4.2 mmole/liter) which suggested that hepatic fatty acid oxidation was impaired. Urinary dicarboxylic acids were elevated during illness or fasting. Total carnitine levels were low in plasma (18-25 mumole/liter), liver (200-500 nmole/g), and muscle (500-800 nmole/g); however, treatment with L-carnitine failed to correct the defect in ketogenesis. Studies on ketone production from fatty acid substrates by liver tissue in vitro showed normal rates from short-chain fatty acids, but very low rates from all medium and long-chain fatty acid substrates. These results suggested that the defect was in the mid-portion of the intramitochondrial beta-oxidation pathway at the medium-chain acyl-CoA dehydrogenase step. A new assay for the electron transfer flavoprotein-linked acyl-CoA dehydrogenases was used to test this hypothesis. This assay follows the decrease in electron transfer flavoprotein fluorescence as it is reduced by acyl-CoA-acyl-CoA dehydrogenase complex. Results with octanoyl-CoA as substrate indicated that patients had less than 2.5% normal activity of medium-chain acyl-CoA dehydrogenase. The activities of short-chain and isovaleryl acyl-CoA dehydrogenases were normal; the activity of long-chain acyl-CoA dehydrogenase was one-third normal. These results define a previously unrecognized inherited metabolic disorder of fatty acid oxidation due to deficiency of medium-chain acyl-CoA dehydrogenase.
Behavior and diabetes care.
Juvenile diabetes presents both the child and the family with psychosocial challenges. Control of the illness and the development of the diabetic child depend on how effectively the family meets these challenges. Maladaptive family interaction can lead to behavioral difficulties as well as poor diabetic control. Problems of recurrent ketoacidosis and noncompliance are highlighted with case histories.
Radioimmunoassays of hidden viral antigens.
Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and thus may elude detection. We describe a solid-phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA are detected.
A practical method for screening psychiatric disorder in children with speech and language disorders.
Children with speech and language disorders have been found to have a prevalence rate of psychiatric disorder of 50%. The authors sought to develop an efficient screening procedure to distinguish such children who have psychiatric disorder and those who do not. Cutoff scores for easily administered parent and teacher behavior rating questionnaires were investigated in a population of 256 children with speech and language disorders and known presence or absence of psychiatric disorder. It was learned that when the questionnaires are used together, a cutoff score of 31 or greater on either questionnaires are used together, a cutoff score of 31 or greater on either questionnaire has a positive predictive value of 74.1% and a negative predictive value of 76.1%. This screening method shows promise in assisting speech pathologists in comprehensive evaluation and treatment planning for children with speech and language disorders.
Developmental, social and behavioral characteristics of speech and language disordered children.
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Psychiatric disorder in children with different types of communication disorders.
Children presenting to a community speech clinic were divided into three major groups according to type of communication disorder: a pure speech disorder, a pure language disorder, and a disorder of both speech and language. Psychiatric evaluations of the three groups of children were done employing interviews with the parents, interviews with the children, and questionnaires from the children's teachers and parents. It was found that the prevalence of psychiatric disorder was highest in the language-disordered group and lowest in the speech-disordered group. Development disorders were also most common in the language-disordered group and least common in the speech-disordered group. The types of psychiatric disorders found in the three groups of children also differed. The implications of these findings are discussed.
Radioimmunoassays of hidden viral antigens.
Antigens corresponding to infectious agents may be present in biological specimens only in a cryptic form bound to antibodies and, thus, may elude detection. We describe a solid phase technique for separation of antigens from antibodies. Immune complexes are precipitated from serum by polyethylene glycol, dissociated with NaSCN, and adsorbed onto nitrocellulose or polystyrene supports. Antigens remain topographically separated from antibodies after removal of NaSCN and can be detected with radiolabeled antibodies. Genomes from viruses immobilized on nitrocellulose can be identified by nucleic acid hybridization. Nanogram quantities of sequestered hepatitis B surface and core antigens and picogram amounts of hepatitis B virus DNA were detected. Antibody-bond adenovirus, herpesvirus, and measles virus antigens were discerned by the procedure.