Search PubMed⌕ Search

Biomedical subjects

J Munson

Publications and source records attributed to J Munson.

16 recordsLinked to original sources

Evidence for multiple loci from a genome scan of autism kindreds.

We performed a genome-wide linkage scan using highly polymorphic microsatellite markers. To minimize genetic heterogeneity, we focused on sibpairs meeting the strict diagnosis of autism. In our primary analyses, we observed a strong linkage signal (P=0.0006, 133.16 cM) on chromosome 7q at a location coincident with other linkage studies. When a more relaxed diagnostic criteria was used, linkage evidence at this location was weaker (P=0.01). The sample was stratified into families with only male affected subjects (MO) and families with at least one female affected subject (FC). The strongest signal unique to the MO group was on chromosome 11 (P=0.0009, 83.82 cM), and for the FC group on chromosome 4 (P=0.002, 111.41 cM). We also divided the sample into regression positive and regression negative families. The regression-positive group showed modest linkage signals on chromosomes 10 (P=0.003, 0 cM) and 14 (P=0.005, 104.2 cM). More significant peaks were seen in the regression negative group on chromosomes 3 (P=0.0002, 140.06 cM) and 4 (P=0.0005, 111.41 cM). Finally, we used language acquisition data as a quantitative trait in our linkage analysis and observed a chromosome 9 signal (149.01 cM) of P=0.00006 and an empirical P-value of 0.0008 at the same location. Our work provides strong conformation for an autism locus on 7q and suggestive evidence for several other chromosomal locations. Diagnostic specificity and detailed analysis of the autism phenotype is critical for identifying autism loci.

Adolescent↗

Brain structural abnormalities in young children with autism spectrum disorder.

OBJECTIVE: To explore the specific gross neuroanatomic substrates of this brain developmental disorder, the authors examine brain morphometric features in a large sample of carefully diagnosed 3- to 4-year-old children with autism spectrum disorder (ASD) compared with age-matched control groups of typically developing (TD) children and developmentally delayed (DD) children. METHODS: Volumes of the cerebrum, cerebellum, amygdala, and hippocampus were measured from three-dimensional coronal MR images acquired from 45 children with ASD, 26 TD children, and 14 DD children. The volumes were analyzed with respect to age, sex, volume of the cerebrum, and clinical status. RESULTS: Children with ASD were found to have significantly increased cerebral volumes compared with TD and DD children. Cerebellar volume for the ASD group was increased in comparison with the TD group, but this increase was proportional to overall increases in cerebral volume. The DD group had smaller cerebellar volumes compared with both of the other groups. Measurements of amygdalae and hippocampi in this group of young children with ASD revealed enlargement bilaterally that was proportional to overall increases in total cerebral volume. There were similar findings of cerebral enlargement for both girls and boys with ASD. For subregion analyses, structural abnormalities were observed primarily in boys, although this may reflect low statistical power issues because of the small sample (seven girls with ASD) studied. Among the ASD group, structural findings were independent of nonverbal IQ. In a subgroup of children with ASD with strictly defined autism, amygdalar enlargement was in excess of increased cerebral volume. CONCLUSIONS: These structural findings suggest abnormal brain developmental processes early in the clinical course of autism. Research currently is underway to better elucidate mechanisms underlying these structural abnormalities and their longitudinal progression.

Amygdala↗

Leukemia inhibitory factor determines the growth status of injured adult sensory neurons.

Conditioning injury to adult mammalian sensory neurons enhances their regeneration potential. Here we show that leukemia inhibitory factor (LIF) is a fundamental component of the conditioning response. Conditioning injury in vivo significantly increases the intrinsic growth capacity of sensory neurons in vitro from LIF+/+ mice. This conditioning effect is significantly blunted in sensory neurons from LIF-/- mice. Enhanced growth is rescued in vitro in LIF-/- mice by the addition of exogenous LIF, and the effect blocked by human LIF-05, an LIF receptor antagonist. Furthermore, we demonstrate that LIF promotes elongating but not arborizing neurite outgrowth in vitro and is required for normal regeneration of injured adult sensory neurons in vivo. LIF is also functionally protective to peptidergic sensory neurons after nerve damage in vivo. Our results indicate that the alteration in intrinsic growth status of injured sensory neurons depends, at least in part, on LIF.

Animals↗

Effects of dorsolateral spinal lesions on stretch reflex threshold and stiffness in awake cats.

Measurements of threshold angle and incremental dynamic stiffness (IDS) were derived from triceps surae stretch reflexes, elicited by ramp and hold flexion at the ankle joint of four cats that were tested while awake. Stretch reflexes were assessed from trials that began from different ankle joint start positions or were matched using a post-hoc analysis for initial background force during testing sessions before and following unilateral lesions of the dorsolateral funiculus at levels ranging from T13 to L3. Unilateral lesions of the dorsolateral funiculus (DLF) produced significant ipsilateral decreases in stretch reflex threshold and increases in reflex gain, measured as incremental dynamic stiffness (IDS). ANCOVA testing indicated that the reduction in threshold, but not the increase in IDS, was dependent upon the level of background force. Reflex testing from different start angles demonstrated that DLF lesions diminished the correlation between threshold and IDS. Intravenous infusion of ketamine dose-dependently reduced IDS, compared with testing in the unanaesthetized state. Postoperative reflex testing during infusion of ketamine at 22.2 mg/kg per h, when electromyographic responses were reduced to 24% of control levels, abolished differences in IDS between the ipsilateral and contralateral hindlimbs. These and related observations suggest that the postoperative increase in IDS in awake animals was not due to an increase in passive stiffness.

Anesthetics, Dissociative↗

T-cell receptor V beta gene segment expression in diisocyanate-induced occupational asthma.

BACKGROUND: Diisocyanates are the most common cause of occupational asthma induced by low-molecular-weight chemicals. The disease appears to be immunologically mediated but is independent of IgE antibody synthesis. An underlying genetic susceptibility is suggested by the fact that the disease only develops in approximately 5% to 10% of exposed workers. OBJECTIVE: The study was designed to determine whether disease susceptibility is influenced by HLA and T-cell receptor V beta gene segment usage. METHODS: T-cell receptor V beta repertoires were quantitated by using primer pairs specific for V beta gene segments in conjunction with a common C beta region primer. One group of workers with diisocyanate-induced occupational asthma produced diisocyanate-specific IgG and IgE antibodies, whereas the other group did not produce specific antibodies. Occupational asthma was previously confirmed by either workplace challenge or laboratory specific diisocyanate bronchoprovocation. Control groups consisted of diisocyanate-exposed workers who were free of symptoms, patients with nonoccupational asthma, and unexposed subjects who were free of symptoms. RESULTS: Lymphocytes from workers with diisocyanate-induced occupational asthma had significantly decreased V beta 1 and V beta 5 gene segment expression before in vitro exposure to diisocyanates, compared with control groups. Percent V beta 1 and V beta 5 gene segment expression was selectively increased when peripheral blood mononuclear cells were stimulated in vitro with diisocyanate-conjugated proteins. Low-resolution HLA class II phenotyping revealed no significant differences in the distribution of HLA-DR or HLA-DQ alleles between diisocyanate-induced occupational asthma and control groups. CONCLUSIONS: These findings are consistent with a hypothesis that antigen-specific T-cell subpopulations may be sequestered in the lungs of workers with diisocyanate-induced occupational asthma and clonally expand after further exposure to diisocyanates.

Asthma↗

The management of temperature during cardiopulmonary bypass: effect on neuropsychological outcome.

Laboratory studies demonstrate that mild degrees of brain cooling (2 degrees C to 5 degrees C) confer substantial protection from ischemic brain injury, and that mild elevation of brain temperature can be markedly deleterious. During hypothermic cardiopulmonary bypass (CPB) patients are made hypothermic and then rewarmed at a time when they are exposed to neurological insults. Our studies show that during rewarming, peak brain temperatures near 39 degrees C often are achieved inadvertently. We hypothesize that maintaining brain temperature < or = 34 degrees C during and after CPB will reduce the incidence of postoperative neuropsychological deficits. We present safety data from a study of 30 patients assigned either to conventional hypothermic CPB with rewarming or a protocol where brain temperature is raised only to 34 degrees C at the time of separation from CPB. There was no difference in bleeding, cardiac morbidity, or time to extubation between groups. We designed a neuropsychological test battery to detect postoperative neuropsychological deficits and tested its usefulness in a preliminary sample of 15 patients undergoing hypothermic CPB. We found patient acceptability and compliance were good. Sensitivity also seemed adequate in that 30% of patients were identified as having deteriorated at 1 week postoperatively compared to preoperatively, a result similar to that reported by others. Clinical trials of the efficacy of mild hypothermia in modulating brain injury in humans are needed before techniques of CPB can be designed to optimize neuroprotection.

Aged↗

Clinical presentation of PTSD in World War II combat veterans.

Clinicians have increasingly recognized posttraumatic stress disorder (PTSD) among Vietnam veterans, but the disorder may be easily overlooked among World War II combat veterans. The authors review recent studies of PTSD in older veterans and describe five cases that illustrate the diverse clinical presentations of PTSD in this population. Symptoms included anxiety, cognitive and somatic complaints, depression, alcohol dependence, and amnestic periods. Despite the varied presentations, a fairly consistent patient profile emerged. Patients avoided reminders of war, showed an exaggerated startle response, and experienced restless sleep and chronic anxiety. Factors associated with exacerbations of symptoms were retirement and reminders of war experiences. Although past studies have emphasized resuppression of the trauma, the authors encourage a flexible approach to treatment, including exploratory techniques.

Adaptation, Psychological↗

Visual artifacts in chromatically subsampled images.

Colors sampled in an array of pixels were converted into various luminance-chrominance representations, and the chrominance values were spatially subsampled to achieve a compression of the data. For viewing, the chrominance values were reinterpolated and then transformed back to RGB. For each of a range of image types and color spaces, we varied the chromatic sample spacing to determine how much compression would be possible before perceptual artifacts appeared, as determined by a panel of individual viewers. The spacing at which an image was mistaken half the time for a remembered original depended on image content and also on the color representation. Some color spaces, such as hue-lightness-saturation, a polar-coordinate color space, are inherently ill suited for chrominance averaging and produce noticeable artifacts on almost any image. Likewise, some images cannot be subsampled satisfactorily, regardless of the color space used. In general, however, images with 16-fold reduction in the amount of chrominance information (that is, a factor of 4 in each spatial direction) are still satisfactory in appearance.

Color↗

Regulation of cerebral blood flow velocity in nonasphyxiated, very low birth weight infants with hyaline membrane disease.

Previous studies of cerebral blood flow (CBF) and blood flow velocity regulation in stressed neonates, both term and preterm, have suggested that CBF is pressure passive. These studies are in conflict with data obtained from fetal and newborn animals. To determine if autoregulation of CBF is present in preterm infants, we studied eight very low birth weight infants (gestational age, 29.1 +/- 1.5 weeks; birth weight, 1117 +/- 278 g), all of whom had hyaline membrane disease that necessitated mechanical ventilation. None of the infants suffered from perinatal asphyxia, intraventricular hemorrhage, or patent ductus arteriosus. All infants demonstrated appropriate changes in cerebral blood flow velocity (CBFV) in response to changes in arterial oxygen content and pCO2. CBFV was not affected by changes in systemic mean arterial blood pressure. The data indicate that nonasphyxiated very low birth weight infants regulate their CBF in a manner similar to that observed in adults.

Blood Flow Velocity↗

Hemangioendothelioma presenting as posterior mediastinal mass in a child.

A case of a five-month-old child who had a posterior mediastinal mass that was found to be a benign hemangioendothelioma is reported. This is the first reported case of this tumor in this location. Benign hemangioendothelioma should be considered in the differential diagnosis of posterior mediastinal mass in children.

Diagnosis, Differential↗

A strategy for measuring local public health practice.

The national health objectives for the year 2000 call for 90% of the population to be served by a local health department (LHD) that is effectively addressing the core functions of public health. Achieving this objective requires approved definitions for effectiveness as well as a system for ascertainment. In 1990 when this objective was established, no baseline data were available, and no accepted methods of measuring health department effectiveness were in use. Our approach to the development of a surveillance system to measure the effectiveness of LHDs has been to translate the three core public health functions characterized by the Institute of Medicine and the 10 practices delineated by the Centers for Disease Control and Prevention (CDC) and the national public health practice organizations into practice performance measures that could be judged as met or not met at the level of a jurisdiction served by a LHD. As part of our effort to develop a surveillance system to measure local public health practice, performance measures that characterize the 10 public health practices and their related core functions were developed and field-tested with state local health liaison officials and local health departments over a two-year period. Obtaining input from these sources is essential to establishing their validity and is a critical aspect of building nationwide consensus for appropriate measures of effective local public health practice. The results of these efforts led to the establishment of a proposed surveillance instrument comprising 10 performance standards and 29 associated indicators. We describe two approaches to its use.

Community Health Services↗

Roles for state-level local health liaison officials in local public health surveillance and capacity building.

In 27 state health agencies, local health liaison units or officials (LHLOs) are formally assigned responsibility for fostering a close working relationship between the state health agency and local health departments (LHDs). Yet in most other states, other agency staff carry out these responsibilities informally. Even where formal LHLOs exist, the assigned functions and specific activities vary, with little consistency across states other than serving as a potential or, in most cases, a real and vital linkage between LHDs and the state agency. This linkage places the LHLO in a unique position to have extensive knowledge, data, and information on LHD activities and to play an important role in assessing and improving local public health practice. This report examines aspects of the LHLO-LHD relationship in terms of potential LHLO roles in LHD practice surveillance and capacity building. Surveys of LHLOs and LHDs indicate that both support the development of surveillance tools to measure LHD effectiveness as a means to enhance capacity building efforts. Although LHLOs may not know or have the specific information immediately available to assess local public health practice for LHDs in their state, they report being able to obtain the information if necessary and with sufficient time. Further, LHDs are willing to share information concerning local public health practice with their state health department, particularly with their state LHLO. These findings suggest that LHLOs could be extensively involved in surveillance strategies beyond merely collecting and aggregating information provided by LHDs.

Administrative Personnel↗