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Biomedical subjects

C Lord

Publications and source records attributed to C Lord.

At least 19 recordsLinked to original sources
PubMed2006

Hippocampal volume is as variable in young as in older adults: implications for the notion of hippocampal atrophy in humans.

Previous studies in humans have shown the presence of an age-related reduction of hippocampal (HC) volume, as well as the presence of reduced HC volume in psychiatric populations suffering from schizophrenia, depression or post-traumatic stress disorder. Altogether, these data suggested that aging or psychiatric disease can have neurotoxic effects on the hippocampus, and lead to HC atrophy. However, these two sets of findings imply that HC volume in young healthy adults should present less variability than HC volume in older adults and psychiatric populations. In the present study, we assessed HC volume in 177 healthy men and women aged from 18 to 85 years of age. We show that the dispersion around the mean of HC volume is not different in young and older adults, so that 25% of young healthy adults present HC volume as small as the average participants aged 60 to 75 years. This shows that HC volume is as variable in young as in older adults and suggests that smaller HC volume attributed to the aging process in previous studies could in fact represent HC volume determined early in life. We also report that within similar age groups, the percentage of difference in HC volume between the individuals with the smallest HC volume (smallest quartile) and the group average is greater than the percentage of difference reported to exist between psychiatric populations and normal control in recent meta-analyses. Taken together, these results confront the notion of hippocampal atrophy in humans and raise the possibility that pre-determined inter-individual differences in HC volume in humans may determine the vulnerability for age-related cognitive impairments or psychopathology throughout the lifetime.

Adolescent↗
PubMed2006

A novel nonsense mutation in the EYA1 gene associated with branchio-oto-renal/branchiootic syndrome in an Afrikaner kindred.

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder characterized by the associations of hearing loss, branchial arch defects and renal anomalies. Branchiootic (BO) syndrome is a related disorder that presents without the highly variable characteristic renal anomalies of BOR syndrome. Dominant mutations in the human homologue of the Drosophila eyes absent gene (EYA1) are frequently the cause of both BOR and BO syndromes. We report a South African family of Afrikaner descent with affected individuals presenting with pre-auricular abnormalities and either hearing loss or bilateral absence of the kidneys. Genetic analysis of the pedigree detected a novel EYA1 heterozygous nonsense mutation in affected family members but not in unaffected family members or a random DNA panel. Through mutational analysis, we conclude that this particular mutation is the cause of BOR/BO syndrome in this family as a result of a truncation of the EYA1 protein that ablates the critical EYA homologous region. To the best of our knowledge, this is the first case of BOR/BO syndrome reported in Africa or in those of the Afrikaner descent.

Base Sequence↗
PubMed2004

Perceptions of general environmental problems, willingness to expend federal funds on these problems, and concerns regarding the Los Alamos National Laboratory: Hispanics are more concerned than Whites.

Perceptions about general environmental problems, governmental spending for these problems, and major concerns about the US Department of Energy's Los Alamos National Laboratory (LANL) were examined by interviewing 356 people attending a gun show in Albuquerque, New Mexico. The hypothesis that there are differences in these three areas as a function of ethnicity was examined. We predicted that if differences existed, they would exist for all three evaluations (general environmental problems, government spending, and environmental concerns about LANL). However, this was not the case; there were fewer ethnic differences concerning LANL. Hispanics rated most general environmental problems higher than Whites and rated their willingness to expend federal funds higher than Whites, although all groups gave a lower score on willingness than on concern. Further, the congruence between these two types of ratings was higher for Hispanics than for others. In general, the concerns expressed by subjects about LANL showed few ethnic differences, and everyone was most concerned about contamination. These data indicate that Hispanics attending a gun show are equally or more concerned than others about environmental problems generally but are not more concerned about LANL. The data can be useful for developing future research and stewardship plans and for understanding general environmental problems and their relationship to concerns about LANL. More generally, they indicate that the attitudes and perceptions of Hispanics deserve increased study in a general population.

Conservation of Natural Resources↗
PubMed2004

Hypernatraemic dehydration in Jamaican breastfed neonates: a 12-year review in a baby-friendly hospital.

A 12-year retrospective review of neonates admitted with hypernatraemic dehydration to the neonatal unit of the University Hospital of the West Indies was conducted between 1 January 1990 and 31 December 2001. Twenty-four infants fulfilled the criteria for hypernatraemic dehydration. Nineteen (79%) women were either nulliparous or primiparous with a mean (SD) age of 26.9 (4.4) yrs. Modal length of hospital stay for mothers was 24 hrs. Twenty (83.3%) infants were exclusively breastfed. Mean (SD) age at presentation was 7.4 (3.8) days. Mean (SD) percentage weight loss between birth and presentation was 18.9% (6.3). Mean (SD) serum sodium at presentation was 164.8 (13.9) mmol/L. Babies visited at home by nurses had a lower mean serum sodium, were less dehydrated and were significantly less acidiotic. Their mean (SD) length of hospital stay was also significantly less [4.2 (1.4) days] than those who were not visited [7.9 (3.8) days] (p < 0.05). Complications occurred in 19 (79%) of infants and included renal failure (19, 79%), seizures (3, 13%) and intraventricular haemorrhage (1, 4%), and one died (4%). Hypernatraemic dehydration is an uncommon complication of failure to establish breastfeeding but is associated with severe morbidity and mortality. Education programmes are needed to increase awareness amongst health-care workers and mothers in order to prevent the problem.

Acidosis↗
PubMed2003

Perceptual indicators of environmental health, future land use, and stewardship.

There are important linkages between the health of humans and the environment, restoration of degraded lands, and long-term stewardship of public lands, yet most environmental indicators deal only with assessing the physical and biological aspects of ecosystems. In this article, we examine the ratings of perceptions of several environmental problems for their utility as indicators of environmental quality, and examine perceptions of future land use by people interviewed in Santa Fe, New Mexico, near the Department of Energy's (DOE) Los Alamos National Laboratory (LANL). Overall, people with lower incomes rated environmental problems as more severe than others, were more willing to spend federal funds to solve them, and were consistent in their ratings of severity of environmental problems and their willingness to spend federal funds. Cleaning up LANL and other Department of Energy sites, received the highest rating for expenditure of federal funds. The highest rated future uses for DOE sites were for recreation and for National Environmental Research Parks. People with less education generally gave higher ratings to most future land uses for DOE than did those with more education. However, those with higher education gave higher ratings to nuclear reprocessing, and nuclear material storage. Where there were differences, the people interviewed at Santa Fe rated all environmental problems (except pesticides) as more severe than did those previously interviewed in Albuquerque (located farther from the LANL site), and they were more willing to spend federal funds on these problems. Ratings for all future land uses did not differ between the Santa Fe and Albuquerque respondents. These perception-based indicators show general agreement among people living close and farther away from LANL with respect to cleaning up LANL and the future land uses for the site. These indicators should be considered by regulators, site personnel, and policy makers in future management and land use decisions.

Adult↗
PubMed2002

Exposure of South Carolinians to commercial meats and fish within their meat and fish diet.

There has been considerable interest in the public's exposure to a variety of contaminants through the consumption of wild fish and game, yet there is little information on consumption of commercial meats and fish, or the relationship between commercial and self-caught fish. We conducted a dietary survey in 1999 to estimate exposure levels of 464 individuals from people attending the Palmetto Sportsmen's Classic. Mean consumption was similar for beef, chicken/turkey, and wild-caught fish, and much lower for pork and store-bought fish, and still lower for restaurant fish. There were no ethnic differences in the consumption of most commercial fish and meats, although the differences for chicken approached significance. There were significant ethnic differences in consumption of wild-caught fish. Women ate significantly less of all meat types, except store-bought fish. People over 45 ate less beef than younger people, and people younger than 32 ate significantly more chicken than others. There were no significant differences in consumption patterns as a function of income, except for chicken and wild-caught fish; people with higher incomes ate more chicken than others, and people with lower incomes ate more wild-caught fish than others. When all wild-caught and commercial fish and meats are considered, there are significant differences only for ethnicity and gender. Blacks consume significantly more fish than Whites, and men consume significantly more than women.

Adult↗
PubMed2002

Transmission disequilibrium mapping at the serotonin transporter gene (SLC6A4) region in autistic disorder.

The serotonin transporter gene (SLC6A4, MIM 182138) is a candidate gene in autistic disorder based on neurochemical, neuroendocrine studies and the efficacy of potent serotonin transporter inhibitors in reducing ritualistic behaviors and related aggression. An insertion/deletion polymorphism (5-HTTLPR) in the promoter region and a variable number of tandem repeat polymorphism (VNTR) in the second intron, were previously identified and suggested to modulate transcription. Six previous family-based association studies of SLC6A4 in autistic disorder have been conducted, with four studies showing nominally significant transmission disequilibrium and two studies with no evidence of nominally significant transmission disequilibrium. In the present study, TDT was conducted in 81 new trios. A previous finding of transmission disequilibrium between a haplotype consisting of the 5-HTTLPR and intron 2 VNTR was replicated in this study, but not preferential transmission of 5-HTTLPR as an independent marker. Because of inconsistent transmission of 5-HTTLPR across studies, SLC6A4 and its flanking regions were sequenced in 10 probands, followed by typing of 20 single nucleotide polymorphisms (SNPs) and seven simple sequence repeat (SSR) polymorphisms in 115 autism trios. When individual markers were analyzed by TDT, seven SNP markers and four SSR markers (six SNPs, 5-HTTLPR and the second intron VNTR from promoter 1A through intron 2 of SLC6A4, one SSR from intron 7 of SLC6A4, one SNP from the bleomycin hydrolase gene (BLMH, MIM 602403) and one SSR telomeric to BLMH) showed nominally significant evidence of transmission disequilibrium. Four markers showed stronger evidence of transmission disequilibrium (TDT(max) P = 0.0005) than 5-HTTLPR.

Autistic Disorder↗
PubMed2002

Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism.

Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V(1a) receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5' flanking region of the V1a gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5' flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5' flanking region and the coding region and identified 10 single nucleotide polymorphisms.

Autistic Disorder↗
PubMed2001

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↗
PubMed2001

A genomewide screen for autism susceptibility loci.

We report the analysis of 335 microsatellite markers genotyped in 110 multiplex families with autism. All families include at least two "affected" siblings, at least one of whom has autism; the remaining affected sibs carry diagnoses of either Asperger syndrome or pervasive developmental disorder. Affected sib-pair analysis yielded multipoint maximum LOD scores (MLS) that reach the accepted threshold for suggestive linkage on chromosomes 5, X, and 19. Nominal evidence for linkage (point-wise P<.05) was obtained on chromosomes 2, 3, 4, 8, 10, 11, 12, 15, 16, 18, and 20, and secondary loci were found on chromosomes 5 and 19. Analysis of families sharing alleles at the putative X chromosomal linked locus and one or more other putative linked loci produced an MLS of 3.56 for the DXS470-D19S174 marker combination. In an effort to increase power to detect linkage, scan statistics were used to evaluate the significance of peak LOD scores based on statistical evidence at adjacent marker loci. This analysis yielded impressive evidence for linkage to autism and autism-spectrum disorders with significant genomewide P values <.05 for markers on chromosomes 5 and 8 and with suggestive linkage evidence for a marker on chromosome 19.

Asperger Syndrome↗
PubMed2001

Quantifying the phenotype in autism spectrum disorders.

Twin and family studies suggest that familial transmission in autism extends to a spectrum of social and behavioral deficits that characterize individuals who have significant impairments within the autism spectrum, but do not meet formal criteria for autistic disorder. Standardized diagnostic instruments, including the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS-WPS Edition), offer the opportunity to quantify deficits across the autism spectrum, controlling effects of language and cognitive delay, in individuals with significant impairments. It is suggested that quantitative measures of social reciprocity and repetitive behaviors and interests, with separate quantification of expressive language level and nonverbal intelligence, most accurately reflect the range of behavioral phenotypes in autism spectrum disorders.

Autistic Disorder↗
PubMed2001

B cell receptor-stimulated mitochondrial phospholipase A2 activation and resultant disruption of mitochondrial membrane potential correlate with the induction of apoptosis in WEHI-231 B cells.

Cross-linking of the Ag receptors on the immature B cell lymphoma, WEHI-231, leads to growth arrest and apoptosis. We now show that although commitment to such B cell receptor (BCR)-mediated apoptosis correlates with mitochondrial phospholipase A(2) activation, disruption of mitochondrial function, and ATP depletion, it is executed independently of caspase activation. First, we demonstrate a pivotal role for mitochondrial function in determining B cell fate by showing up-regulation of cytosolic phospholipase A(2) expression, induction of mitochondrial phospholipase A(2) activity, arachidonic acid-mediated collapse of mitochondrial transmembrane inner potential (Delta psi(m)), and depletion of cellular ATP under conditions of apoptotic, but not proliferative, signaling via the BCR. Importantly, disruption of Delta psi(m), ATP depletion, and apoptosis can be prevented by rescue signals via CD40 or by Delta psi(m) stabilizers such as antimycin or oligomycin. Second, we show that commitment and postmitochondrial execution of BCR-mediated apoptosis are not dependent on caspase activation by demonstrating that such apoptotic signaling does not induce release of cytochrome c from the mitochondria or activation of effector caspases, as evidenced by poly(ADP-ribose) polymerase or Bcl-x(L) cleavage. Indeed, apoptotic signaling via the BCR in WEHI-231 B cells does not stimulate the activation of caspase-3 and, consistent with this, BCR-mediated disruption of Delta psi(m) and commitment to apoptosis take place in the presence of caspase inhibitors. In contrast, BCR signaling induces the postmitochondrial activation of cathepsin B, and resultant apoptosis is blocked by the cathepsin B inhibitor, (23,35)trans-epoxysuccinyl-L-leucylamindo-3-methylbutane ethyl ester (EST) suggesting a key role for this executioner protease in Ag receptor-driven apoptosis of WEHI-231 immature B cells.

Adenosine Triphosphate↗
PubMed2001

How much observational data is enough? An empirical test using marital interaction coding.

Using three different samples of couples (clinic, nondistressed community, and engaged), we found that 15 minutes was sufficient to witness enough behavior to make reliable (i.e., internally consistent) estimations of most Rapid Marital Interaction Coding System (Heyman & Vivian, 1993) code frequencies. Ten minutes is sufficient for many codes of interest. The ease in which "how much time is necessary" calculations can be made should entice behavioral investigators from a variety of content areas to publish such figures. By empirically investigating a factor that in most fields becomes reified through convention, investigators can conduct observational research that is both maximally efficient and maximally scientifically defensible.

Journal Article↗
PubMed2001

Double-blind, placebo-controlled study of amantadine hydrochloride in the treatment of children with autistic disorder.

OBJECTIVE: To test the hypothesis that amantadine hydrochloride is a safe and effective treatment for behavioral disturbances--for example, hyperactivity and irritability--in children with autism. METHOD: Thirty-nine subjects (intent to treat; 5-19 years old; IQ > 35) had autism diagnosed according to DSM-IV and ICD-10 criteria using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. The Aberrant Behavior Checklist-Community Version (ABC-CV) and Clinical Global Impressions (CGI) scale were used as outcome variables. After a 1-week, single-blind placebo run-in, patients received a single daily dose of amantadine (2.5 mg/kg per day) or placebo for the next week, and then bid dosing (5.0 mg/kg per day) for the subsequent 3 weeks. RESULTS: When assessed on the basis of parent-rated ABC-CV ratings of irritability and hyperactivity, the mean placebo response rate was 37% versus amantadine at 47% (not significant). However, in the amantadine-treated group there were statistically significant improvements in absolute changes in clinician-rated ABC-CVs for hyperactivity (amantadine -6.4 versus placebo -2.1; p = .046) and inappropriate speech (-1.9 versus 0.4; p = .008). CGI scale ratings were higher in the amantadine group: 53% improved versus 25% (p = .076). Amantadine was well tolerated. CONCLUSIONS: Parents did not report statistically significant behavioral change with amantadine. However, clinician-rated improvements in behavioral ratings following treatment with amantadine suggest that further studies with this or other drugs acting on the glutamatergic system are warranted. The design of these and similar drug trials in children with autistic disorder must take into account the possibility of a large placebo response.

Adolescent↗
PubMed2001

Multisite, double-blind, placebo-controlled trial of porcine secretin in autism.

OBJECTIVE: To examine the efficacy of intravenous porcine secretin for the treatment of autistic disorder. METHOD: Randomized, double-blind, placebo-controlled, crossover design. Fifty-six subjects with autistic disorder received either a secretin or placebo infusion at baseline and the other substance at week 4. Subjects were given the Autism Diagnostic Observation Schedule (ADOS) and other pertinent developmental measures at baseline and at weeks 4 and 8 to assess drug effects. RESULTS: For the primary efficacy analysis, change of ADOS social-communication total score from week 0 to week 4, no statistically significant difference was obtained between placebo (-0.8 +/- 2.9) and secretin groups (-0.6 +/- 1.4; t54 = 0.346, p < .73). The other measures showed no treatment effect for secretin compared with placebo. CONCLUSION: There was no evidence for efficacy of secretin in this randomized, placebo-controlled, double-blind trial.

Autistic Disorder↗