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Biomedical subjects

J M Fletcher

Publications and source records attributed to J M Fletcher.

At least 91 records · Page 5Linked to original sources
PubMed1996

Behavioral outcomes after pediatric closed head injury: relationships with age, severity, and lesion size.

This study investigated the behavioral outcomes and adaptive functioning of 138 children with mild to severe closed head injury in the 6- to 16-year age range. Each child was evaluated with the Personality Inventory for Children-Revised. A subset of this sample (n = 77) received the Vineland Adaptive Behavior Scales. Results revealed little evidence for group differences based on severity of closed head injury on scales associated with psychopathology on the Personality Inventory for Children-Revised. However, children with severe closed head injury were viewed as experiencing more difficulties than children with mild-moderate closed head injury on those components of the Personality Inventory for Children-Revised most closely associated with cognitive functions. In addition, on the Vineland Adaptive Behavior Scales, severely injured children had lower scores on the Communication and Socialization scales than children with mild-moderate injury. Relationships between the size of frontal and extrafrontal lesions from concurrent magnetic resonance imaging and behavioral outcomes were not apparent. This study suggests that outcome measures assessing adaptive behavior and cognitive functions are more sensitive to severity of closed head injury than parent-based scales of internalizing and externalizing psychopathology.

Adolescent↗
PubMed1995

Sex differences in the functional organization of the brain for language.

A much debated question is whether sex differences exist in the functional organization of the brain for language. A long-held hypothesis posits that language functions are more likely to be highly lateralized in males and to be represented in both cerebral hemispheres in females, but attempts to demonstrate this have been inconclusive. Here we use echo-planar functional magnetic resonance imaging to study 38 right-handed subjects (19 males and 19 females) during orthographic (letter recognition), phonological (rhyme) and semantic (semantic category) tasks. During phonological tasks, brain activation in males is lateralized to the left inferior frontal gyrus regions; in females the pattern of activation is very different, engaging more diffuse neural systems that involve both the left and right inferior frontal gyrus. Our data provide clear evidence for a sex difference in the functional organization of the brain for language and indicate that these variations exist at the level of phonological processing.

Adult↗
PubMed1995

A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1.

We describe a detailed physical map of human chromosome 11, extending from the distal part of p13 through the entirety of p14 to proximal p15.1. The primary level of mapping is based on chromosome breakpoints that divide the region into 20 intervals. At higher resolution YACs cover approximately 12 Mb of the region, and in many places overlapping cosmids are ordered in contiguous arrays. The map incorporates 18 known genes, including precise localization of the GTF2H1 gene encoding the 62-kDa subunit of TFIIH. We have also localized four expressed sequences of unknown function. The physical map incorporates genetic markers that allow relationships between physical and genetic distance to be examined, and similarly includes markers from a radiation hybrid map of 11. The cytogenetic location of cosmids has been examined on high-resolution banded chromosomes by fluorescence in situ hybridization, and FLpter values have been determined. The map therefore fully integrates physical, genic, genetic, and cytogenetic information and should provide a robust framework for the rapid and accurate assignment of new markers at a high level of resolution in this region of 11p.

Base Sequence↗
PubMed1995

Non-ketotic hyperglycinaemia presenting as pachygyria.

A 2-day-old infant with lethargy and hypoventilation had pachygyria and agenesis of the corpus callosum on CT scan. Increased concentrations of glycine in plasma and CSF, together with an increased CSF/plasma ratio, confirmed a clinical diagnosis of non-ketotic hyperglycinaemia. This is the first report of pachygyria in this disorder, although agenesis of the corpus callosum is well recognized, and non-specific gyral malformations have been described previously. The specific diagnosis of an inborn error of metabolism in infants with structural brain malformations is of critical importance for accurate genetic counseling.

Amino Acid Metabolism, Inborn Errors↗
PubMed1995

GIP and GLP-1(7-36)amide secretion in response to intraduodenal infusions of nutrients in pigs.

Investigation of nutrient stimulation of two gut hormones GIP (glucose dependent insulotropic polypeptide) and GLP-1(7-36)amide (the active truncated form of glucagon-like peptide-1) is made difficult by the differential control of gastric emptying. Direct nutrient infusion into the duodenum was therefore carried out on three female pigs. The infusates consisted of saline (0.85 g or 1.7 g/100 ml); glucose (20 g or 40 g/100 ml); fat (30 g or 60 g/500 ml) and glucose/fat (20 g and 30 g or 40 g and 60 g per 1000 ml). Plasma glucose levels were elevated as expected by glucose or glucose/fat infusions, and they were not affected by the presence of fat in the infusate. Insulin secretion was stimulated in the presence of glucose or glucose/fat. Plasma triacylglycerol was elevated following fat and glucose/fat infusions. The greatest stimulus for GIP secretion was glucose/fat (P < 0.05); fat alone was a poor stimulus for GIP secretion, but glucose was a potent stimulus. GLP-1(7-36)amide was moderately stimulated by glucose and markedly stimulated by fat and glucose/fat infusions (P < 0.05). We conclude that, in pigs, dual nutrient infusion of glucose/fat is a strong stimulus for both GIP and GLP-1(7-36)amide secretion. The hormones therefore have the potential to play an important physiological role, both in the stimulation of insulin secretion and in adipose tissue metabolism in pigs.

Analysis of Variance↗
PubMed1995

Plasma and intestinal concentrations of GIP and GLP-1 (7-36) amide during suckling and after weaning in pigs.

Plasma concentrations of glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1[7-36]amide) were measured after milk ingestion in 15-18 day old piglets and after weaning diet ingestion in 33 day old piglets weaned at 21 days. Intestinal concentrations of these two hormones were also measured in unsuckled piglets of less than 24 h of age, and piglets whose ages corresponded with those used for plasma measurements. Suckling piglets showed a moderate glycaemic and insulinaemic response to milk ingestion. Plasma GIP and GLP-1(7-36)amide levels were significantly elevated at 1 and 3-h post-prandially. Weaned piglets showed a much more marked glucose and insulin response to meal ingestion. Plasma GIP and GLP-1(7-36)amide levels were again significantly elevated at 1 and 3 h in these animals. The mean plasma GIP response was greater in the weaned animals compared with the suckling animals at the time points investigated. The plasma GLP-1(7-36)amide response in contrast was significantly greater at 1 h in the suckling animals. In comparison, GIP concentrations in acid ethanol extracts of the small intestine were significantly higher during suckling and GLP-1(7-36)amide concentrations significantly higher after weaning. The circulating levels of both hormones seen during suckling and after weaning were far higher than those previously reported in humans. We conclude that both milk ingestion and the weaning diet are capable of stimulating GIP and GLP-1(7-36)amide in piglets and suggest that the levels of both hormones seen in this study may be important in adipose tissue metabolism at this time.

Animals↗
PubMed1995

Investigations into the actions of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1(7-36)amide on lipoprotein lipase activity in explants of rat adipose tissue.

The direct actions of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1(7-36)amide and insulin on lipoprotein lipase activity in explants of rat epididymal adipose tissues were investigated. Lipoprotein lipase was extracted into the incubation medium by heparin release of lipoprotein lipase and measured by fatty acid release from a glyceroltriolein emulsion. Insulin and glucose-dependent insulinotropic polypeptide caused a significant stimulation of lipoprotein lipase activity over a dose range of 0.25-4 nmol/L and 4-8 nmol/L, respectively. Explants incubated in the presence of both insulin and glucose-dependent insulinotropic polypeptide (at 0.5 and 4 nmol/L, respectively) showed levels of lipoprotein lipase activity significantly greater than that seen with either hormone alone. Neither insulin- nor glucose-dependent insulinotropic polypeptide-stimulated lipoprotein lipase was modified by the presence of the antibiotic actinomycin-D in the incubation medium, indicating that these two hormones exert their actions on the pre-existing cellular pool of lipoprotein lipase. Glucagon-like polypeptide-1(7-36)amide, over a dose range of 1-8 nmol/L, did not stimulate lipoprotein lipase activity. This study indicates that glucose-dependent insulinotropic polypeptide, in addition to stimulating insulin secretion, has a direct biological action on adipose tissue and in vivo, together with insulin, may promote lipoprotein lipase activity postprandially.

Adipose Tissue↗
PubMed1995

Behavioral adjustment of children with hydrocephalus: relationships with etiology, neurological, and family status.

Examined the relationship of hydrocephalus and behavioral adjustment in three groups of 5- to 7-year-old children (N = 84) with a history of early hydrocephalus (spina bifida, prematurity, aqueductal stenosis) and three non-hydrocephalic comparison groups (spina bifida, prematurity, normals). Results revealed no significant group differences on measures of behavioral adjustment and a variety of family and sociodemographic variables. Children with hydrocephalus were more likely to meet criteria for behavior problems, obtained lower scores on measures of adaptive behavior, and perceived themselves as less physically competent. Categorical modeling analyses showed that hydrocephalus and its treatment, gender, family variables, and motor skills were related to the presence of behavior problems.

Analysis of Variance↗
PubMed1995

Verbal and nonverbal skill discrepancies in children with hydrocephalus: a five-year longitudinal follow-up.

Compared verbal and nonverbal skills of 65 children ages 5 to 7 years, with a history of shunted hydrocephalus (n = 26), arrested hydrocephalus (n = 11), and no hydrocephalus (n = 28), over a 5-year period. Comparison of these skills in 4 assessments revealed poorer average nonverbal than verbal skills on measures from the McCarthy Scales of Children's Abilities, the Wechsler Intelligence Scales for Children-Revised (WISC-R), and composites of neuropsychological skills for the shunted hydrocephalus group in comparison to the arrested-hydrocephalus and no hydrocephalus groups. There were higher rates of significant discrepancies between WISC-R Verbal IQ (VIQ) and Performance IQ (PIQ), with PIQ < VIQ in the shunted group. However, relatively few children exhibited significant discrepancies on multiple test occasions. The poorer performance of the shunted hydrocephalus group could not be attributed to motor demands of the nonverbal tasks.

Cerebrospinal Fluid Shunts↗
PubMed1995

Regional localisation of 19 brain expressed sequence tags to human chromosome 11 using PCR amplification of somatic cell hybrid DNAs.

Expressed sequence tags (ESTs) provide an efficient route to the identification of genes involved in normal development and in disease. PCR amplification of somatic cell hybrid DNAs was used to localise 22 brain-derived ESTs to subregions of human chromosome 11. Problems encountered with the standardised PCR conditions were overcome by optimising the annealing temperatures and the use of "touchdown" PCR. Amplification of the correct target sequence allowed the mapping of 19 ESTs, 8 to the short arm and 11 to the long arm of chromosome 11. No definitive localisation could be determined for the three remaining ESTs.

Animals↗
PubMed1995

Defining and classifying learning disabilities and attention-deficit/hyperactivity disorder.

This paper provides an overview of current conceptualizations of learning disabilities and ADHD, a conceptual framework critical for defining and classifying each disorder and for distinguishing each disorder from the other and from other, less common problems of childhood. At a most basic level, reading disability or dyslexia (the most common and best defined of the learning disabilities) and ADHD represent two distinct disorders that may frequently cooccur in the same unfortunate child but that can be clearly distinguished from one another. Reading disability represents a disorder of cognitive functioning. In contrast, ADHD is defined by the child's behavior as perceived by the child's parents and teachers; ADHD thus refers to a disorder affecting primarily the behavioral domain. Within the last decade, considerable progress has been made in our understanding of reading and reading disability. Converging evidence from several lines of investigation now indicates that reading ability conforms to a normal distribution model, so that there is a continuum of reading ability and reading disability. Children along this continuum differ by degree but not in kind. Cutoff points may be instituted to segment this continuous distribution, but these will be arbitrary and will not reflect any natural joints in nature; there is no second mode or "hump" in the distribution of reading ability. The normal model of reading and reading disability indicates that reading disability is related to normal reading ability, that there is a seamless transition from good to poor reading ability. Awareness of this relationship is critical to our approach to understanding the basis of reading disability.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Frontal lobe changes after severe diffuse closed head injury in children: a volumetric study of magnetic resonance imaging.

In view of the pathophysiology and biomechanics of severe closed head injury (CHI) in children, we postulated that the frontal lobes sustain diffuse injury, even in the absence of focal brain lesions detected by magnetic resonance imaging (MRI). This study quantitated the morphological effects of CHI on the frontal lobes in children who sustained head trauma of varying severity. The MRI findings of 14 children who had sustained severe CHIs (Glasgow Coma Scale score of < or = 8) were compared with the findings in a matched group of 14 children having sustained mild head injuries (Glasgow Coma Scale score of 13-15). The patients ranged in age from 5 to 15 years at the time of their MRIs, which were acquired at least 3 months postinjury. MRI findings revealed no focal areas of abnormal signal in the frontal lobes. Volumetric analysis disclosed that the total prefrontal cerebrospinal fluid increased and the gray matter volume decreased in the patients with severe CHI, relative to the mildly injured comparison group. Gray matter volume was also reduced in the orbitofrontal and dorsolateral regions of the brains of children with severe CHI, relative to the children who sustained mild head trauma. These volumetric findings indicate that prefrontal tissue loss occurs after severe CHI in children, even in the absence of focal brain lesions in this area. Nearly two-thirds of the children who sustained severe CHIs were moderately disabled after an average postinjury interval of 3 years or more, whereas 12 of the 14 patients with mild CHIs attained a good recovery (2 were moderately disabled) by the time of study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Brain morphology in normal and dyslexic children: the influence of sex and age.

Morphometric magnetic resonance imaging techniques were used to compare the convolutional surface area of the planum temporale, temporal lobe volume and superior surface area, and an estimate of overall brain volume in a homogeneous sample of 17 dyslexic children (7 girls) and 14 nonimpaired children (7 girls). Substantial sex differences were apparent for all measured regions, with all the measurements in boys being significantly larger. Age, even within the narrow range employed here (7.5-9.7 years), was positively correlated with the size of each brain region. While initial analyses suggested smaller left hemisphere structures in dyslexics compared to control subjects, subsequent analyses controlling for age and overall brain size revealed no significant differences between dyslexics and nonimpaired children on a variety of measures, in particular surface area and symmetry of the planum temporale. We suggest that differences in subject characteristics (i.e., sex, age, handedness, and definition of dyslexia) as well as procedural variations in the methods used to acquire images and to define and measure anatomical regions of interest such as the planum temporale all may play an important role in explaining apparent discrepant results in the neuroimaging literature on dyslexia.

Age Factors↗
PubMed1994

Effect of dietary lipids and endocrine changes on polyunsaturated fatty acids in phospholipids of pancreas and brown adipose tissue of obese and lean rats.

Obese (fa/fa) rats fed on control diet have lower proportions of linoleic acid (18:2n-6) and/or arachidonic acid (20:4n6) in IBAT and pancreas phospholipids compared with lean (Fa/-) rats. Lower stearic acid (18:0) to oleic acid (18:1n-9) mean ratios in fa/fa compared with Fa/- suggest enhanced delta 9-desaturase activity in the former. 18:2/20:4 mean ratios in pancreas, but not IBAT, are indicative of a reduced delta 6-desaturase activity in fa/fa rats. Absolute amounts of phospholipids (mg/unit tissue wt) were 2-fold greater in IBAT of fa/fa compared with Fa/- rats, irrespective of their diet. This was reflected in greater absolute amounts of 18:2n-6 and 20:4n-6 only in HSO and HTO fa/fa groups, but not in the control group. Adrenalectomy (Adx) or T3 treatment also modified phospholipid fatty acid composition of IBAT and pancreas phospholipids in animals fed on the control diet with fa/fa rats more sensitive to endocrine induced changes. In fa/fa rats T3 treatment increased docosahexaenoic acid (22:6n-3) in IBAT of both phenotypes compared with the control, but this effect was evident only in fa/fa and not Fa/- pancreas. T3 treatment also increased docosapentaenoic acid (22:5n-3) in IBAT from, both phenotypes, but no 22:5n-3 was evident in the pancreatic tissue of these animals. ADX also increased 22:6n-3 in the IBAT of fa/fa (Fa/- values were less than 1%) but not in the pancreas of fa/fa or Fa/-. ADX modified the relative proportions of 18:0 to 18:1 and 18:2 to 20:4 in IBAT and pancreas of fa/fa in a way that indicated decreased delta 9-desaturase and increased delta 6-desaturase activities; these effects tended toward normal again in pancreas of fa/fa rats on corticosterone replacement (CST).

Adipose Tissue, Brown↗
PubMed1994

Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly.

Mutation or deletion of the PAX6 gene underlies many cases of aniridia. Three lines of evidence now converge to implicate PAX6 more widely in anterior segment malformations including Peters' anomaly. First, a child with Peters' anomaly is deleted for one copy of PAX6. Second, affected members of a family with dominantly inherited anterior segment malformations, including Peters' anomaly are heterozygous for an R26G mutation in the PAX6 paired box. Third, a proportion of Sey/+ Smalleye mice, heterozygous for a nonsense mutation in murine Pax-6, have an ocular phenotype resembling Peters' anomaly. We therefore propose that a variety of anterior segment anomalies may be associated with PAX6 mutations.

Amino Acid Sequence↗
PubMed1994

Neuropsychological characteristics of children with Tourette syndrome: evidence for a nonverbal learning disability?

In this study the neuropsychological characteristics of thirty-one 6 to 16-year-old children with Tourette Syndrome (TS) were compared to 20 normal siblings and 10 children with arithmetic disabilities (AD) who were comparable in age and socioeconomic status. Unlike the sibling group, neuropsychological profiles of the TS and AD groups were expected to reflect nonverbal learning disabilities (NLD). The three groups performed generally within the average range on academic and cognitive measures. Like the AD children, the TS group demonstrated poorer performance on written arithmetic tasks with comparatively better word reading and written word spelling. Unlike the AD group, who demonstrated generalized nonverbal deficiencies, children with TS demonstrated reduced performance on visual-motor and expressive language measures as well as measures of complex cognition. These results are suggestive of an "output" subtype of learning disability and support theories that implicate the mesocortical dopaminergic system in the pathophysiology of TS.

Adolescent↗
PubMed1994

Dissociation between delayed alternation and memory after pediatric head injury: relationship to MRI findings.

This study investigated the usefulness of a delayed alternation task in characterizing the cognitive sequelae of closed head injury in children and adolescents. Verbal learning and memory (California Verbal Learning Test) were also studied for comparison. Sixty-two closed head injury patients (mean age, 9.6 years), who were studied after an average postinjury interval of 20 months, were divided according to both their lowest postresuscitation Glasgow Coma Scale score (3 to 8 versus 9 to 15) and age range (5 to 7 years versus 8 to 16 years) at the time of testing. Magnetic resonance imaging was performed to evaluate the relationship of focal brain lesions to cognitive and memory performance. Fifty-six neurologically normal children (mean age, 9.9 years) were tested on the same measures. The results disclosed no relationship between delayed alternation performance and severity of injury. In contrast, verbal memory was impaired in the severely-injured patients, relative to both controls and less severely-injured patients. Frontal lobe (but not extrafrontal) lesion size incremented the Glasgow Coma Scale score in predicting verbal memory, but there was no relationship between focal brain lesions and delayed alternation performance. In contrast to the tendency for more efficient delayed alternation performance in the 5- to 7-year-old subjects than in the 8- to 16-year-old subjects, verbal memory significantly improved with age in the closed head injury and control groups. Notwithstanding our essentially negative findings for delayed alternation, it is possible that this task may be useful for assessing frontal lobe injury in younger children or infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗