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Biomedical subjects

K Pierce

Publications and source records attributed to K Pierce.

At least 19 recordsLinked to original sources

Unusual brain growth patterns in early life in patients with autistic disorder: an MRI study.

OBJECTIVE: To quantify developmental abnormalities in cerebral and cerebellar volume in autism. METHODS: The authors studied 60 autistic and 52 normal boys (age, 2 to 16 years) using MRI. Thirty autistic boys were diagnosed and scanned when 5 years or older. The other 30 were scanned when 2 through 4 years of age and then diagnosed with autism at least 2.5 years later, at an age when the diagnosis of autism is more reliable. RESULTS: Neonatal head circumferences from clinical records were available for 14 of 15 autistic 2- to 5-year-olds and, on average, were normal (35.1 +/- 1.3 cm versus clinical norms: 34.6 +/- 1.6 cm), indicative of normal overall brain volume at birth; one measure was above the 95th percentile. By ages 2 to 4 years, 90% of autistic boys had a brain volume larger than normal average, and 37% met criteria for developmental macrencephaly. Autistic 2- to 3-year-olds had more cerebral (18%) and cerebellar (39%) white matter, and more cerebral cortical gray matter (12%) than normal, whereas older autistic children and adolescents did not have such enlarged gray and white matter volumes. In the cerebellum, autistic boys had less gray matter, smaller ratio of gray to white matter, and smaller vermis lobules VI-VII than normal controls. CONCLUSIONS: Abnormal regulation of brain growth in autism results in early overgrowth followed by abnormally slowed growth. Hyperplasia was present in cerebral gray matter and cerebral and cerebellar white matter in early life in patients with autism.

Adolescent↗

Atypical patterns of cerebral motor activation in autism: a functional magnetic resonance study.

BACKGROUND: Early neurodevelopmental pathogenesis in autism potentially affects emerging functional maps, but little imaging evidence is available. METHODS: We studied eight male autistic and eight matched normal subjects, using functional magnetic resonance imaging during visually paced finger movement, compared to a control condition (visual stimulation in the absence of motor response). RESULTS: Groupwise analyses showed activation in contralateral perirolandic cortex, basal ganglia, and thalamus, bilateral supplementary motor area, and ipsilateral cerebellum for both groups. However, activations were less pronounced in the autism group. Direct group comparisons demonstrated greater activation in perirolandic and supplementary motor areas in the control group and greater activation (or reduced deactivation) in posterior and prefrontal cortices in the autism group. Intraindividual analyses further showed that strongest activations were consistently located along the contralateral central sulcus in control subjects but occurred in locations differing from individual to individual in the autism group. CONCLUSIONS: Our findings, though based on a rather small sample, suggest abnormal individual variability of functional maps and less distinct regional activation/deactivation patterns in autism. The observations may relate to known motor impairments in autism and are compatible with the general hypothesis of disturbances of functional differentiation in the autistic cerebrum.

Adolescent↗

Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism.

BACKGROUND: Although limited environmental exploration in autism is an obvious behavioral feature and may be a manifestation of "restricted interests" as described in DSM-IV criteria, there have been no behavioral or neurobiological studies of this important aspect of the disorder. Given consistent reports of cerebellar abnormality in autism, combined with animal research showing a relationship between exploration and the cerebellum, this study aimed to test the possible link between cerebellar abnormality and exploration in autism. METHODS: The relationship between visuospatial exploration, stereotyped motor movements, and magnetic resonance imaging measures of the cerebellar vermis, whole brain volume, and frontal lobes in 14 autistic and 14 normal children was investigated. Children were exposed to a large room with several exploration containers and instructed to play. Exploration behavior was videotaped and scored for percentage of time engaged in exploration, number of containers explored, as well as stereotyped movements. RESULTS: Children with autism spent significantly less time in active exploration and explored fewer containers overall than normal children. Measures of decreased exploration were significantly correlated with the magnitude of cerebellar hypoplasia of vermal lobules VI-VII in the autistic children, but no relationship to vermis size was found with normal control children. Further, measures of rates of stereotyped behavior were significantly negatively correlated with area measures of cerebellar vermis lobules VI-VII and positively correlated with frontal lobe volume in the autism sample. CONCLUSIONS: Reduced environmental exploration and repetitive behavior may have particularly important developmental consequences for children with autism because it may lead them to miss learning opportunities that fall outside their scope of interest. Our findings represent the first documented link between the restricted range of interests and stereotyped behaviors pathognomonic of autism and particular neuroanatomic sites.

Autistic Disorder↗

Event-related brain response abnormalities in autism: evidence for impaired cerebello-frontal spatial attention networks.

Although under some conditions the attention-related late positive event-related potential (ERP) response (LPC) is apparently normal in autism during visual processing, the LPC elicited by visuospatial processing may be compromised. Results from this study provide evidence for abnormalities in autism in two components of the LPC generated during spatial processing. The early frontal distribution of the LPC which may reflect attention orienting was delayed or missing in autistic subjects during conditions in which attention was to peripheral visual fields. The later parietal distribution of the LPC which may be associated with context updating was smaller in amplitude in autistic subjects regardless of attention location. Both abnormalities suggest disruption of function in spatial attention networks in autism. Evidence that the cerebellar abnormalities in autism may underlie these deficits comes from: (1) similar results in ERP responses and spatial attention deficits in patients with cerebellar lesions; (2) brain-behavior correlations in normally functioning individuals associating the size of the posterior cerebellar vermis and the latency of the frontal LPC; and (3) a previously reported complementary correlation between the size of the posterior vermal lobules and spatial orienting speed. Although the scalp-recorded LPC is thought to be cortically generated, it may be modulated by subcortical neural activity. The cerebellum may serve as a modulating influence by affecting the task-related antecedent attentional process. The electrophysiological abnormalities reported here index spatial attention deficits in autism that may reflect cerebellar influence on both frontal and parietal spatial attention function.

Adolescent↗

Face processing occurs outside the fusiform 'face area' in autism: evidence from functional MRI.

Processing the human face is at the focal point of most social interactions, yet this simple perceptual task is difficult for individuals with autism, a population that spends limited amounts of time engaged in face-to-face eye contact or social interactions in general. Thus, the study of face processing in autism is not only important because it may be integral to understanding the social deficits of this disorder, but also, because it provides a unique opportunity to study experiential factors related to the functional specialization of normal face processing. In short, autism may be one of the only disorders where affected individuals spend reduced amounts of time engaged in face processing from birth. Using functional MRI, haemodynamic responses during a face perception task were compared between adults with autism and normal control subjects. Four regions of interest (ROIs), the fusiform gyrus (FG), inferior temporal gyrus, middle temporal gyrus and amygdala were manually traced on non-spatially normalized images and the percentage ROI active was calculated for each subject. Analyses in Talairach space were also performed. Overall results revealed either abnormally weak or no activation in FG in autistic patients, as well as significantly reduced activation in the inferior occipital gyrus, superior temporal sulcus and amygdala. Anatomical abnormalities, in contrast, were present only in the amygdala in autistic patients, whose mean volume was significantly reduced as compared with normals. Reaction time and accuracy measures were not different between groups. Thus, while autistic subjects could perform the face perception task, none of the regions supporting face processing in normals were found to be significantly active in the autistic subjects. Instead, in every autistic patient, faces maximally activated aberrant and individual-specific neural sites (e.g. frontal cortex, primary visual cortex, etc.), which was in contrast to the 100% consistency of maximal activation within the traditional fusiform face area (FFA) for every normal subject. It appears that, as compared with normal individuals, autistic individuals 'see' faces utilizing different neural systems, with each patient doing so via a unique neural circuitry. Such a pattern of individual-specific, scattered activation seen in autistic patients in contrast to the highly consistent FG activation seen in normals, suggests that experiential factors do indeed play a role in the normal development of the FFA.

Adult↗

Expressed sequence tags for the chicken genome from a normalized, ten-day-old white leghorn whole embryo cDNA library. 2. Comparative DNA sequence analysis of guinea fowl, quail, and turkey genomes.

Accelerated efforts to develop a high-utility chicken genome map have resulted in the development of resources that may be useful for genetic analysis in other economically important poultry species. Here we describe a total of 26 comparative genomic DNA sequences (CGS) for the guinea fowl, Japanese quail, and domestic turkey developed using 10 primer pairs specific for 10 previously reported, unique, chicken expressed sequence tags (EST). The total length of CGS developed for each of the three species was 4,193, 4,597, and 6,057 bp in quail, turkey, and guinea fowl, respectively. About 70% of the CGS showed significant sequence similarity to reference database sequences, including the reference chicken EST and other avian and nonavian genes. A majority of the between-species comparisons of the CGS from all but two primer pairs were significant and ranged from 81 to 99%. The percentage similarity of the CGS appears to be a function of phylogenetic relatedness and was generally higher for comparisons between the chicken, quail, and turkey and lower between the guinea fowl and chicken, quail, or turkey. Maximum likelihood estimation of the phylogenetic relationships using CGS from two primer pairs also showed a closer relationship, as expected, among chicken, quail, and turkey than between guinea fowl and either chicken, quail, or turkey. Within the guinea fowl, quail, and turkey CGS developed, the total number of single nucleotide polymorphisms detected was 28, 17, and 14, respectively. Together, these resources represent tools that will facilitate genetic analysis of species that have been studied very little and our understanding of their genomes and genome evolution.

Animals↗

Prevalence and assessment of attention-deficit/hyperactivity disorder in primary care settings.

Research literature relating to the prevalence of attention-deficit/hyperactivity disorder (ADHD) and co-occurring conditions in children from primary care settings and the general population is reviewed as the basis of the American Academy of Pediatrics clinical practice guideline for the assessment and diagnosis of ADHD. Epidemiologic studies revealed prevalence rates generally ranging from 4% to 12% in the general population of 6 to 12 year olds. Similar or slightly lower rates of ADHD were revealed in pediatric primary care settings. Other behavioral, emotional, and learning problems significantly co-occurred with ADHD. Also reviewed were rating scales and medical tests that could be employed in evaluating ADHD. The utility of using both parent- and teacher-completed rating scales that specifically assess symptoms of ADHD in the diagnostic process was supported. Recommendations were made regarding the assessment of children with suspected ADHD in the pediatric primary care setting.

Attention Deficit Disorder with Hyperactivity↗

Progressive vascular remodeling and reduced neointimal formation after placement of a thermoelastic self-expanding nitinol stent in an experimental model.

Despite the improvements afforded by intracoronary stenting, restenosis remains a significant problem. The optimal physical properties of a stent have not been defined. We compared the vascular response to a thermoelastic self-expanding nitinol stent with a balloon-expandable tubular slotted stainless steel stent in normal porcine coronary arteries. Twenty-two stents (11 nitinol and 11 tubular slotted) were implanted in 11 miniature swine. The nitinol stents were deployed using the intrinsic thermal properties of the metal, without adjunctive balloon dilation. The tubular slotted stents were implanted using a noncompliant balloon with a mean inflation pressure of 12 atm. Intravascular ultrasound (IVUS) and histology were used to evaluate the vascular response to the stents. The mean cross-sectional area (CSA) of the nitinol stents (mm2) as measured by IVUS increased from 8.13 +/- 1.09 at implant to 9.10 +/- 0.99 after 28 days (P = 0.038), while the mean CSA of the tubular slotted stents was unchanged (7.84 +/- 1.39 mm2 vs. 7.10 +/- 1.07 mm2, P = 0.25). On histology at 3 days, the tubular slotted stents had more inflammatory cells adjacent to the stent wires (5.7 +/- 1.5 cells/0.1 mm2) than the nitinol (3.9 +/- 1.3 cells/0.1 mm2, P = 0.016). The tubular slotted also had increased thrombus thickness (83 +/- 85 microm) than the nitinol stents (43 +/- 25 microm, P = 0.0014). After 28 days, the vessel injury score was similar for the nitinol (0.6 +/- 0.3) and the tubular slotted (0.5 +/- 0.1, P = 0.73) designs. The mean neointimal area (0.97 +/- 0.46 mm2 vs. 1.96 +/- 0.34 mm2, P = 0.002) and percent area stenosis (15 +/- 7 vs. 33 +/- 7, P = 0.003) were significantly lower in the nitinol than in the tubular slotted stents, respectively. We conclude that a thermoelastic nitinol stent exerts a more favorable effect on vascular remodeling, with less neointimal formation, than a balloon-expandable design. Progressive intrinsic stent expansion after implant does not appear to stimulate neointimal formation and, therefore, may provide a mechanical solution to prevent in-stent restenosis.

Alloys↗

California's county hospitals and the University of California graduate medical education system. Current issues and future directions.

California's county hospitals train 45% of the state's graduate medical residents, including 33% of residents in the University of California system. This paper describes the interrelationships of California's county hospitals and the University of California (UC) graduate medical education (GME) programs, highlighting key challenges facing both systems. The mission of California's county health care systems is to serve all who need health care services regardless of ability to pay. Locating UC GME programs in county hospitals helps serve the public missions of both institutions. Such partnerships enhance the GME experience of UC residents, provide key primary care training opportunities, and ensure continued health care access for indigent and uninsured populations. Only through affiliation with university training programs have county hospitals been able to run the cost-effective, quality programs that constitute an acceptable safety net for the poor. Financial stress, however, has led county hospitals and UC's GME programs to advocate for reform in both GME financing and indigent care funding. County hospitals must participate in constructing strategies for GME reform to assure that GME funding mechanisms provide for equitable compensation of county hospitals' essential role. Joint advocacy will also be essential in achieving significant indigent care policy reform.

California↗

The association of HLA-DR15 and intermediate uveitis.

PURPOSE: To evaluate the association between human leukocyte antigen (HLA-DR15) specificity and intermediate uveitis. METHODS: Eighteen patients diagnosed with intermediate uveitis underwent HLA-DR15 serotyping. Additionally, DNA-based phenotyping for a specific HLA-DR15 allele was performed in four patients. The clinical features of HLA-DR15-positive intermediate uveitis were compared with those of HLA-DR15-negative intermediate uveitis. RESULTS: Thirteen of 18 patients (72%) were positive for HLA-DR15. The frequency of the HLA-DR15 specificity in intermediate uveitis patients was significantly higher than in the control subjects (relative risk, 6.36; P < .001). Each of four patients tested carried the specific allele, DR beta 1*1501, which has been associated with multiple sclerosis. In the HLA-DR15-positive group were four patients (31%) with coexisting multiple sclerosis or optic neuritis, one patient with coexisting narcolepsy, and three patients (23%) with a family history of multiple sclerosis. Retinal periphlebitis, especially if bilateral, was a frequent ophthalmoscopic finding in HLA-DR15-positive intermediate uveitis. CONCLUSIONS: This study identifies a significant association between intermediate uveitis and the HLA-DR15 specificity. Patients who are HLA-DR15-positive and have intermediate uveitis may have systemic findings of another HLA-DR15-related disorder. Intermediate uveitis may belong to a constellation of HLA-DR15-related disorders, which includes multiple sclerosis, optic neuritis, and narcolepsy.

Adolescent↗

Social perception in children with autism: an attentional deficit?

Research suggests that the attentional deficits found in children with autism may be related to impairments in social functioning (e.g., Courchesne et al., 1994a, 1994b; Lewy & Dawson, 1992; Schreibman & Lovaas, 1973). In the present investigation, 14 children with autism, 14 mentally handicapped, and 14 typically functioning children participated in a study designed to investigate the effects of number of social cues on the ability to interpret social situations. Participants were shown videotaped vignettes of child-child interactions in which the number of cues leading to the correct interpretation of the story varied from one to four (i.e., tone, content, nonverbal, or nonverbal with object). Subjects were then asked a series of questions which varied in degree of complexity. Overall, results indicated that children with autism performed as well as both groups of comparison subjects on general attention questions (i.e., identification of number and gender of interactants) and social perception questions relating to stories containing one cue. However, children with autism performed more poorly than both comparison groups on social perception questions relating to stories containing multiple cues. Results are discussed in terms of an attentional dysfunction hypothesis of autism.

Adolescent↗

Multiple peer use of pivotal response training to increase social behaviors of classmates with autism: results from trained and untrained peers.

Two children with autism and 8 typical peers participated in a study designed to replicate an earlier finding of successful social-skills intervention for children with autism using peer-implemented pivotal response training (PRT) and to assess the effects of using multiple peer trainers on generalization of treatment effects. During training, peers were taught PRT strategies using didactic instruction, modeling, role playing, and feedback. After treatment, children with autism engaged in increased levels of social behavior.

Autistic Disorder↗

Unrelated donor bone marrow transplantation to treat severe aplastic anaemia in children and young adults.

Alternative donor bone marrow transplantation (BMT) to treat severe aplastic anaemia (SAA) in children and young adults has been complicated by high rates of graft rejection and severe graft-versus-host disease (GVHD). We hypothesized that increased immunosuppression combined with T-cell depletion of the marrow graft would enable successful use of unrelated donor BMT in this disease. Preconditioning consisted of cytosine arabinoside, cyclophosphamide, and total body irradiation (TBI). T-cell depletion was with the anti-CD3 antibody T10B9. GVHD prophylaxis consisted of cyclosporine A. 28 previously transfused patients were transplanted. Nine donor/recipient pairs were HLA matched. As of 1 January 1996, 15/28 (54%) patients are alive, transfusion independent and well with a range of follow-up of 13 months to 8 years (median 2.75 years). Fatalities include all three patients with nonengraftment and all three patients with grade III/IV GVHD. Other fatalities were due to infections or therapy-related toxicity. The incidence >or= grade II acute GVHD was 28%. These data show that in children with SAA who have failed immunosuppression, unrelated donor BMT offers a reasonable hope of long-term survival.

Adolescent↗

Increasing complex social behaviors in children with autism: effects of peer-implemented pivotal response training.

Two children with autism were taught to engage in a variety of complex social behaviors using peer-implemented pivotal response training (PRT), a set of procedures designed to increase motivation and promote generalization. Typical peers were taught to implement PRT strategies by modeling, role playing, and didactic instruction. After training, peers implemented the procedures in the absence of direct supervision in a classroom environment. After the intervention, both children with autism maintained prolonged interactions with the peer, initiated play and conversations, and increased engagement in language and joint attention behaviors. In addition, teachers reported positive changes in social behavior, with the largest increases in peer-preferred social behavior. Further, these effects showed generality and maintenance. Implications of these findings are discussed.

Autistic Disorder↗

Efficacy of acemannan in treatment of canine and feline spontaneous neoplasms.

Forty-three dogs and cats with spontaneous tumors were treated with the immunostimulating polysaccharide acemannan by intraperitoneal and intralesional routes of administration. Tumors from 26 of these animals showed histopathological evidence of immunological attack as shown by marked necrosis or lymphocytic infiltration. Thirteen showed moderate to marked tumor necrosis or liquefaction. Twenty-one demonstrated lymphoid infiltration, and seven demonstrated encapsulation. Twelve animals showed obvious clinical improvement as assessed by tumor shrinkage, tumor necrosis, or prolonged survival; these included five of seven animals with fibrosarcomas. It is believed that acemannan exerts its antitumor activity through macrophage activation and the release of tumor necrosis factor, interleukin-1, and interferon.

Adjuvants, Immunologic↗

Expression of functional coagulation factor XIII in Escherichia coli.

Coagulation factor XIII is a zymogen that can be activated by thrombin cleavage to a transglutaminase that catalyses the formation of covalent crosslinks between fibrin chains in the final stages of the blood clotting cascade. Although circulating factor-XIII is composed of A and B subunits the catalytic activity is a property of the A subunits. In this study we have constructed a plasmid (pKKF13A) that contains a cDNA encoding the A subunit positioned downstream of a tac promoter. Escherichia coli containing this plasmid produce A subunit protein when grown in the presence of IPTG. The cloned A subunit has been partially purified and characterized. Comparison with A subunits purified from plasma showed that the cloned A subunits were of the same size, assembled as dimers, and had the same native electrophoretic mobility. The cloned A subunits expressed transglutaminase activity with putrescine, dansylcadaverine and casein as substrates, and were able to crosslink fibrin in clots formed from A subunit deficient plasma. These studies have demonstrated that functional recombinant factor XIII A subunit can be produced in E. coli and suggest that recombinant factor XIII can potentially provide a safe and inexhaustible supply for therapeutic use.

Amino Acid Sequence↗