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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The pathogenesis of the mental retardation in phenylketonuria remains obscure. Leucocytes have proved of value in the study of other inborn errors of metabolism. The lymphocyte is a suitable model cell for the study of mammalian metabolism, because of its ability to divide in vitro in response to various stimuli. 2. We have examined the effects of phenylalanine, phenylpyruvate, phenyl-lactate and phenylacetate on the human leucocyte and the resting and phytohaemagglutinin-stimulated rabbit lymphocyte. 3. Phenylpyruvate and phenyl-lactate reduced acetate incorporation into leucocyte lipid by 38% and 48% respectively. Only phenyl-lactate reduced acetate incorporation into the resting and stimulated lymphocyte, by 20% and 34% respectively. 4. Glucose incorporation into leucocyte lipid was unaffected by phenylalanine, phenylpyruvate and phenyl-lactate. Only phenyl-lactate inhibited (46%) the production of CO2 from glucose. 5. Phenylalanine and leucine incorporation into trichloroacetic acid-insoluble material of resting and stimulated lymphocytes was inhibited by phenyl-lactate (10-42%), phenylpyruvate (27-57%) and phenylacetate (19-39%). 6. Uridine incorporation into resting and stimulated cells was inhibited by phenyl-lactate (22-26%), phenylpyruvate (42-52%) and phenylacetate (20%). 7. Thymidine incorporation into resting lymphocytes was reduced by phenyl-lactate, phenylpyruvate, phenylacetate and phenylalanine by 12-26%. Incorporation into the stimulated cell was inhibited by phenylpyruvate and phenyl-lactate (90%) and phenylacetate (66%). 8. Phenylalanine inhibited lymphocyte pyruvate kinase and phenylpyruvate inhibited citrate synthetase. 9. These results are compared with published data relating to experimental hyperphenylalaninaemia and the effects of these metabolites on nervous tissue in vitro.
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PMID:Effect of phenylalanine and its metabolites on the metabolism of leucocytes and lymphocytes. 123 28

Methylmalonate (MMA) accumulates in the tissues of patients with methylmalonic acidaemia, who present severe neurological signs soon after birth and later mental retardation. Attempting to understand the pathophysiology of the disorder, we investigated the effects of MMA on brain glucose uptake, lactate release and CO2 production. Glucose uptake and lactate release were studied by incubating 40 microns wide brain prisms from 15-day-old rats in Krebs-Ringer bicarbonate buffer, pH 7.0, containing 5.0 mmol/L glucose and one of three concentrations of MMA (1.0, 2.5 and 5.0 mmol/L). Controls did not contain MMA in the incubation medium. MMA induced a significant increase of lactate production in a dose-dependent pattern that was proportional to glucose uptake by the brain prisms. We also studied the influence of MMA on brain CO2 production from [2-14C]glucose and [U-14C]acetate by incubating brain prisms in the same buffer in the presence of the substrates with (experimental groups) or without (controls) 5.0 mmol/L MMA. MMA significantly reduced CO2 formation from both substrates.
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PMID:Effect of methylmalonate on in vitro lactate release and carbon dioxide production by brain of suckling rats. 158 80

Literature data on the harmful effects of smoking during pregnancy are reviewed with special emphasis on the fetal growth retardation and delayed changes in child behavior. Intrauterine growth retardation is one of the major causes of low birth weight. It was shown that the birth weight of neonates in smoking mothers can be decreased by 30-396 g. Mass screening data indicate that smoking during pregnancy also increases perinatal mortality (up to 28%). Intrauterine growth retardation was also observed following passive smoking. Inhalation of tobacco smoke by pregnant women was found to increase the fetal heart rate and inhibit fetal movements. Children born from smoking mothers had the higher incidence of asphyxia, cyanosis and hyperactivity. Mass longitudinal studies of children of smoking mothers indicated learning disability, slight mental retardation and insufficient social adaptation by the age of 7 years. Special neurological follow-up study of 326 children revealed frequent minimal brain dysfunction. Pathogenesis of fetal disorders was shown to be associated with impaired adaptation to pregnancy in smoking women. Majority of the constituents of tobacco smoke are capable to pass through the placental-fetal barrier. The most harmful components for fetal development were found to be nicotine and carbon monoxide, which reduce the placental perfusion and blood flow. Exposure to carbon monoxide was shown to increase the level of carboxyhemoglobin and decrease the level of oxyhemoglobin resulting in reduced oxygen supply to fetal tissues and fetal anoxia.
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PMID:[Pathogenesis of fetal growth retardation and behavioral disorders in the progeny caused by smoking during pregnancy]. 265

Nevoid basal cell carcinoma (BCC) syndrome is a genetically linked disorder characterized by multiple BCCs associated with various skeletal abnormalities and sometimes with mental retardation. Because of the large number of lesions, treatment of BCCs in these patients may be extremely difficult. The value of different therapeutic options was assessed in a patient with multiple, disfiguring nevoid BCC syndrome. Surgical excision and split-skin grafting was used to remove three larger tumors. Photodynamic therapy led to healing of flat lesions; small papules within the treated areas, however, did not respond to this type of management. Three nodular BCCs treated with intralesional application of interferon alfa-2b were markedly reduced in size. Still, complete healing could not be achieved. Nodular lesions vaporized with the CO2 laser disappeared and showed no recurrence after 2 years of follow up. Our experience indicates that CO2 laser vaporization of BCCs allows the treatment of a large number of lesions in a single session, and is indicated when surgical treatment is not feasible for all lesions. Photodynamic therapy with 5-amino-levulinic acid may be a valid therapeutic option for flat lesions only. Intralesional application of interferon alfa-2b removes papular lesions of small size.
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PMID:Different treatment modalities for the management of a patient with the nevoid basal cell carcinoma syndrome. 862 34

Mental retardation associated with hypothyroidism may be caused by impairment of brain ketone body-metabolizing enzymes during the suckling period. However, much evidence suggests that, immediately after delivery, lactate, instead of ketone bodies or glucose, may be the best substrate for the brain. In this work, we have studied the effect of experimentally induced congenital hypothyroidism on the rate of lactate, glucose, and 3-hydroxybutyrate utilization in early neonatal brain slices. Methimazole (MMI) administration to the mothers caused a 5.4- and 1.7-fold decrease in neonatal plasma concentrations of L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3), respectively. Propylthiouracil (PTU) administration to the mothers caused a 7.3- and > 2-fold decrease in plasma T4 and T3 concentrations, respectively. MMI-induced hypothyroidism did not significantly modify the rate of lactate, glucose, or 3-hydroxybutyrate oxidation to CO2 and their incorporation into lipids by the neonatal brain. However, PTU-induced hypothyroidism decreased the rate of lactate and glucose oxidation to CO2 and their incorporation into lipids by 17% (p < 0.05). 3-Hydroxybutyrate utilization was not modified by this treatment. Separation by HPLC of the lipids revealed that PTU-mediated inhibition of lipid synthesis from lactate and glucose may be accounted for by specific inhibition of the rate of sterol synthesis (15%, p < 0.05), whereas the rate of phospholipid synthesis was unaffected. These results suggest that the early newborn may develop mechanisms aimed at avoiding the possible brain damage caused by the inhibition of lipid synthesis brought about by mild neonatal hypothyroidism.
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PMID:Fuel utilization by early newborn brain is preserved under congenital hypothyroidism in the rat. 886 77

The development of the fetal central nervous system can be effected by drugs. In this paper we review the neurological consequences of intrauterine exposure to alcohol, cocaine, opiates and marijuana. Ethanol causes the fetal alcohol syndrome: mental retardation, intrauterine and postnatal growth retardation, and peculiar dysmorphic features. Is pathogenesis has been explained on the basis of maternal nutritional deficiencies or due to abnormalities in the conversion of ethanol to aldehyde, or abnormalities in the metabolism of prostaglandins or retinoic acid, the neurotransmitter systems, the neuronal excitotoxic activity, the development of the white matter, the production of gangliosides, and/or genetic regulation cell-cell adhesion. Cocaine has been related to congenital malformations, neurologic abnormalities during the neonatal period and psychomotor and cognitive development deficits. Characteristic dysmorphic features and a higher incidence of the sudden infant death syndrome (SIDS) have also been described. The following mechanisms have been implicated in the pathogenesis: vascular effects, superoxide formation, chelation of calcium ion channels, and abnormalities in the production of glycosphingolipids, the synthesis of DNA, the functioning of neurotransmitter systems, the neuronal growth and differentiation, the neuronal excitotoxic activity and/or the expression of early immediate genes. Opiates produce intrauterine and postnatal growth retardation, neonatal abstinence syndrome, and deficits of the psychomotor and cognitive development. They also increase the incidence of SIDS. The pathogenesis has been related to abnormalities in the sensitivity of the locus ceruleus, the functioning of the neurotransmitter systems, and/or the expression of early immediate genes. Marijuana has been associated with intrauterine growth retardation, dysmorphic features, and abnormalities of the behavior during the neonatal period, the psychomotor and cognitive development, and the sleep. The pathogenesis is thought to be due to an action upon specific receptors, or upon the neurotransmitter systems, and/or to an increase in the production of carbon monoxide. The best treatment of the syndrome of intrauterine exposure to drugs in the prophylaxis. The identification of emotional and drug addiction problems in the mother can avoid disastrous consequences. The care of these children is complex and requires a good pediatric follow-up and an early intervention program while the mother on the parents continue with the drug addiction therapy. The coordinations of all the necessary services with the active participation of social workers, physicians, educators and teachers is crucial for a successful treatment.
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PMID:[Intrauterine exposure to drugs]. 920 93

Fetal alcohol syndrome is one of the leading causes of mental retardation in the United States, but the pathogenesis of the associated brain damage is unknown. We tested the hypothesis that neonatal cerebrovascular responses to CO2 and/or hypoxia may be altered by moderate chronic maternal ethanol exposure early in gestation. We studied 26 newborn lambs (1-4 d old). Their mothers had received daily i.v. infusions of either ethanol (1 g/kg; ethanol concentration = 167 +/- 3 mg/dL; mean +/- SEM) or a similar volume of saline for 3 wk during the first trimester. In nine lambs, we studied cerebral responses to CO2 (saline, n = 4; ethanol, n = 5) and in 17 lambs, cerebral responses to hypoxia (saline, n = 7; ethanol, n = 10). Cerebrovascular responses to CO2 were not different between the groups. However, the cerebral vasodilatory response to hypoxemia was significantly attenuated in the ethanol lambs, such that cerebral O2 delivery was not maintained. During severe hypoxia (arterial PO2 = 30 mm Hg), cerebral blood flow increased 106 +/- 23% (mean +/- SEM) above baseline in the saline-treated group, but increased only 32 +/- 15% above baseline in the ethanol-treated group (p < 0.02). Similarly, cerebrovascular resistance in the saline group decreased 52 +/- 6% from baseline, but decreased only 16 +/- 11% in the ethanol group (p < 0.02). We conclude that moderate maternal ethanol infusion early in pregnancy attenuates neonatal hypoxic, but not CO2, cerebrovascular responsivity.
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PMID:Newborn cerebrovascular responses after first trimester moderate maternal ethanol exposure in sheep. 921 35

Nevoid basal cell carcinoma syndrome is an autosomal dominant condition characterized by multiple basal cell carcinomas, skeletal abnormalities and sometimes mental retardation. The large number of tumors, which are often disfiguring, presents extreme difficulties in the treatment of these patients. Microscopically controlled excision, compared to other modalities (radiation therapy, photodynamic therapy, intralesional interferon alpha-2b) offers the highest cure rate. However, because of the large size and involvement of wide areas of the skin, this approach is sometimes impractical. The ultrapulse CO2 laser with high energy and short pulses achieves char-free ablation of the tumors, bloodless surgical field, minimal nonspecific thermal damage, rapid healing and diminished postoperative pain. Also, a number of lesions can be removed in a single session. We present a 48-year-old man with a 6.5 x 4.5 cm large basal cell carcinoma involving the anterior abdomen and navel area. The central thick portion of the tumor was resected by microscopically controlled excision with 3 stages, and wide thinner peripheral crescentic plaque vaporized with ultrapulse CO2 laser. The laser settings were 300 mJ energy/pulse and 100 W average power, which corresponds to the fluence of 7.5 J/cm2. Computerized pattern generator (ultrascan handpiece) was adjusted to patterns of 3 (circle) and 1 (square) with sizes varying from 5 to 7, and density of 9 (60% overlapping). The tumor was vaporized with 6 passes, all the way to deep reticular dermis. A fifteen month-follow up disclosed no recurrent disease. Subsequent biopsies revealed only a scar with postinflammatory hyperpigmentation. Our experience indicates that combined treatment with microscopically controlled excision and ultrapulse CO2 laser ablation is a suitable modality for the large tumor plaques involving concave and convex areas of the skin respectively. Microscopically controlled excision of thicker, concave portions of basal cell carcinoma plaques, where CO2 laser surgery is less feasible, presents an effective addition that renders this combined modality a successful method for the treatment of nevoid basal cell carcinoma syndrome.
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PMID:Microscopically controlled surgical excision combined with ultrapulse CO2 vaporization in the management of a patient with the nevoid basal cell carcinoma syndrome. 951 2

This report presents the case of a 2-year-old boy who had a bifid epiglottis associated with Joubert's syndrome. He had episodic tachypnea and apnea, inspiratory stridor, aspiration, and growth and mental retardation. Direct laryngoscopy demonstrated agenesis of the right half of the epiglottis and hypertrophied mucosa over the arytenoid cartilage. After the hypertrophied mucosa was partially vaporized with a CO2 laser, the inspiratory stridor soon improved and the aspiration was alleviated. Brain magnetic resonance imaging showed cerebellar vermian agenesis and enlargement of the fourth ventricle.
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PMID:Bifid epiglottis associated with Joubert's syndrome. 1121 29

Enhancement of memory acquisition and recall represents an important pharmacological goal in the treatment of cognitive disorders. In addition to its involvement in pH regulation, HCO3- reabsorption and CO2 expiration, carbonic anhydrase plays a crucial role in signal processing, long-term synaptic transformation and attentional gating of memory storage. Carbonic anhydrase dysfunction impairs cognition and is associated with mental retardation, Alzheimer's disease and aging. The pharmacological profile of carbonic anhydrase has been refined and specific activators have been developed. In this article, an integrated view of the involvement of carbonic anhydrase activity in synaptic plasticity and cognition will be presented, with particular focus on attentional gating of spatial learning and memory.
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PMID:Carbonic anhydrase gating of attention: memory therapy and enhancement. 1183 Feb 65


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