PubMed Health⌕ Search

Biomedical subjects

D C Hughes

Publications and source records attributed to D C Hughes.

At least 19 recordsLinked to original sources
PubMed2006

When physiology becomes pathology: the role of magnetic resonance imaging in evaluating bone marrow oedema in the humerus in elite tennis players with an upper limb pain syndrome.

Upper limb stresses are well recognised in tennis, and the normal physiological responses of the humerus to externally applied forces are well defined. Changes to both the microscopic and macroscopic bony architecture are often not apparent on plain radiographs in the early stages of a stress reaction. Bone scintigraphy is more sensitive, but not very specific to subtle changes, as is computer aided tomography. Magnetic resonance imaging (MRI) scans are now used to assess many musculoskeletal injuries, and may allow earlier recognition of changes. This study reports on eight high level tennis players (seven professionals, one highly ranked amateur), who all presented during the course of the 2002 Australian Open and its lead up events. All had an upper limb pain syndrome centred around the elbow. Each underwent an MRI scan. A group of asymptomatic players also had scans of the same area to serve as controls. All symptomatic patients had various levels of bone marrow oedema in their distal humerus, some with periosteal reactions, although most without. No scans revealed a cortical breach. The management of these reactions is problematic in players on an international circuit, as review is sporadic and not always coordinated. The timetabling of international tournaments means it is difficult for top players to obtain adequate rest to avoid injury. Awareness of this early overuse reaction needs to be raised to allow preventive and therapeutic options to be considered to reduce the incidence of this humeral stress response producing an upper limb pain syndrome.

Adolescent↗
PubMed2005

Cracking the egg: increased complexity in the zona pellucida.

A functional zona pellucida is critical for both fertilization and the early stages of embryo development. Recent data from genomic and proteomic studies have questioned our simplistic view of the zona as being composed of three proteins whose functions are clearly defined. In the human, for example, the zona pellucida is composed of four proteins, not three. The increased complexity of the zona pellucida in humans and other species across the evolutionary tree now demands that we reconsider our reliance on the mouse model for understanding early fertilization events. Additionally, we are now well placed to examine, for the first time, potential defects in zona genes and their proteins associated with defined pathology.

Animals↗
PubMed2004

Four zona pellucida glycoproteins are expressed in the human.

BACKGROUND: The zona pellucida (ZP) is an extracellular glycoprotein matrix which surrounds all mammalian oocytes. Recent data have shown the presence of four human zona genes (ZP1, ZP2, ZP3 and ZPB). The aim of the study was to determine if all four ZP proteins are expressed and present in the human. METHODS: cDNA derived from human oocytes were used to amplify by PCR the four ZP genes. In addition, isolated native human ZP were heat-solubilized, trypsin-digested and subjected to tandem mass spectrometry (MS/MS). RESULTS: All four genes were expressed and the respective proteins present in the human ZP. Moreover, a bioinformatics approach showed that the mouse ZPB gene, although present, is likely to encode a non-functional protein. CONCLUSIONS: Four ZP genes are expressed in human oocytes (ZP1, ZP2, ZP3 and ZPB) and preliminary data show that the four corresponding ZP proteins are present in the human ZP. Therefore, this is a fundamental difference with the mouse model

Amino Acid Sequence↗
PubMed2003

Analysis of fish ZP1/ZPB homologous genes--evidence for both genome duplication and species-specific amplification models of evolution.

The vertebrate egg envelope is composed of a family of related proteins, the zona pellucida (ZP) proteins, which are characterized by the presence of a conserved zona pellucida domain. Analysis of teleost fish ZP gene sequences has demonstrated that there are no direct orthologues of the mammalian ZPB and ZP1 genes, but that teleost fish contain multiple copies of two classes of genes (ZPXa and ZPXb) that are equally related to ZPB and ZP1. The two classes of genes are further distinguished by expression in liver or ovary, respectively, indicating there was probably an initial duplication event, followed by a switch to hepatic expression of one of the paralogues. This switch was followed in some species by additional amplification of one of the paralogues with the subsequent loss of the other. It is proposed that the expansion of the number of ZPXa and ZPXb genes and the acquisition of dual sites of synthesis are the result of an ancient polyploidization event, followed by additional species-specific gene amplifications.

Animals↗
PubMed2001

Alternative splicing of the human VEGFGR-3/FLT4 gene as a consequence of an integrated human endogenous retrovirus.

The vascular endothelial growth factor receptor 3 (VEGFR-3/FLT4) is a receptor tyrosine kinase that regulates angiogenesis and vasculogenesis in response to the binding of the ligands VEGF-C and VEGF-D. Mutations in VEGFR-3 have been identified in patients with primary lymphoedema. It has been noted previously that whilst in the mouse there is only a single Vegfr-3 transcript, in humans there are two transcripts of 5.8 and 4.5 kb, of which the shorter encodes a protein that lacks the C-terminal 65 amino acids. These two isoforms also differ in their biological activity. Analysis of the human VEGFR-3 cDNA and genomic sequence reveals that these two isoforms arise by alternative splicing of the terminal exons. The shorter transcript is generated by splicing into the long terminal repeat of a human endogenous retrovirus located between the last two exons, thus explaining the lack of the shorter transcript in the mouse. The retention of the retroviral sequences in the FLT4 locus suggests that this retrotransposition event has contributed significant additional function to this gene. This provides support for a role for integrated retroviruses in modulating gene activity and participating in evolutionary processes.

Alternative Splicing↗
PubMed2001

A simple diagnostic index for asthma.

BACKGROUND: Asthma is becoming increasingly prevalent and a number of research groups are investigating its genetic and environmental basis. OBJECTIVE: To produce a brief screening tool suitable for determining phenotype in asthma research. METHODS: The scores from eight questions on symptoms and history were obtained from 678 adults and 244 children from high asthma-incidence caucasian families. An independent physician diagnosis was also obtained with the use of a modified NHLBI-CSGA questionnaire and pulmonary function test. Stepwise logistic regression was applied to determine which of the eight questions had greatest predictive value for asthma, and the quality of the resultant models was evaluated using an independent set of 643 adults and 239 children. RESULTS: For adults, the most parsimonious model used responses from three of the eight questions. It had sensitivity and specificity of 0.94 and 0.96, respectively. For children, responses to two questions gave a model with sensitivity and specificity of 0.97. For both age groups, negative predictive values were above 0.87. Positive predictive values were 0.58 and 0.78 for adults and children respectively. The latter emphasize the need for conformation, by physician, of "affected" calls made by this initial screen. CONCLUSION: The brief questionnaires described are potentially useful in a research setting, as a preliminary screening mechanism of low cost. Their use will reduce the numbers of subjects that must undergo detailed phenotyping.

Adolescent↗
PubMed2001

The impact of managed care on children's access, satisfaction, use, and quality of care.

OBJECTIVE: To examine the impact of managed care on children's access, satisfaction, use, and quality of care using nationally representative household survey data. DATA SOURCE: The 1996 Medical Expenditure Panel Survey (MEPS). STUDY DESIGN: Bivariate and multivariate analyses are used to detect independent effects of managed care on access, satisfaction, utilization, and quality of pediatric health services. DATA COLLECTION/EXTRACTION METHODS: Data were obtained from rounds 1, 2, and 3 of the 1996 MEPS. MEPS collects data on health care use, insurance, access, and satisfaction, along with basic demographic and health status information for a representative sample of the U. S. civilian, noninstitutionalized population. Our sample consists of 5,995 children between the ages of 0 and 17. FINDINGS: Among the 18 outcome indicators examined, the bivariate analysis revealed only three statistically significant differences between children enrolled in managed care and children in traditional health plans: children enrolled in managed care were more likely to receive physician services, more likely to have access to office-based care during evening or weekend hours, and less likely to report being very satisfied with overall quality of care. However, after controlling for confounding factors, none of these differences remained statistically significant. CONCLUSIONS: Our findings suggest that there are no statistically significant differences in self-reported outcomes for children enrolled in managed care and traditional health plans. This conclusion is provisional, however, because of limitations in the data set.

Adolescent↗
PubMed2000

Impact of correlated factors on bone density in individuals with a family history of osteoporosis.

Previous studies have suggested that 14-47% of the variation in bone mineral density (BMD) can be predicted using clinical risk factors. The aim of our study was to determine, for the first time, the importance of these factors in individuals with evidence of a genetic predisposition to the disease. The subjects studied were 147 female and 86 male Caucasians, all with a family history of osteoporosis. Linear regression was used to determine whether age, height, weight, and years of reduced estrogen exposure were significant predictors of BMD. Males and females were examined separately, and BMD was measured at the hip and spine. The results show that these risk factors, known to be at work in the general population, are equally important in those with a family history of osteoporosis. It is clear, therefore, that they must be taken into account, and corrected for in genetic studies of the disease.

Adult↗
PubMed2000

The unmet health needs of America's children.

OBJECTIVE: Unmet need for health care is a critical indicator of access problems. Among children, unmet need for care has special significance inasmuch as the failure to obtain treatment can affect health status and functioning in the near- and long-term. The purpose of this study was to present current prevalence estimates and descriptive characteristics of children with unmet health needs using nationally representative household survey data. METHODS: We analyzed 4 years of National Health Interview Survey data spanning 1993 through 1996. Our analysis included 97 206 children <18 years old. Measures of unmet need for medical care, dental care, prescription medications, and vision care were obtained from an adult household member (usually the mother) responding for the child. Bivariate and multivariate analyses were used to assess the degree to which unmet need was related to the demographic and socioeconomic characteristics of the child and family. RESULTS: Overall, 7.3% (4.7 million) of US children experienced at least 1 unmet health care need. Dental care was the most prevalent unmet need. After adjustment for confounding factors, near-poor and poor children were both about 3 times more likely to have an unmet need as nonpoor children (adjusted odds ratio [95% confidence interval] = 2.89 [2.52, 3.32], 3.0 [2.53, 3.56], respectively). Uninsured children were also about 3 times more likely to have an unmet need as privately insured children (adjusted odds ratio [95% confidence interval] = 2. 92 [2.58, 3.32]). CONCLUSIONS: Despite the nation's great wealth, unmet health needs remain prevalent among US children. A combined public policy that addresses financial and nonfinancial barriers to care is required to reduce the prevalence of unmet need for health care.

Adolescent↗
PubMed1999

Identification of the true human orthologue of the mouse Zp1 gene: evidence for greater complexity in the mammalian zona pellucida?

The mammalian zona pellucida is a mixture of glycoproteins, believed to be encoded by three distinct genes, ZP1/ZPB, ZP2/ZPA, and ZP3/ZPC. We have now determined that the true human orthologue of the mouse Zp1 gene is not ZPB, but that there is a distinct human ZP1 gene. Comparison of the human ZP1 and murine Zp1 genes indicates significant conservation of nucleotide and amino acid sequences, of intron-exon size and organisation, and of regulatory sequences. In addition, the mouse and human ZP1 genes are in a region of conserved synteny between human chromosome 11 and mouse chromosome 19.

Animals↗
PubMed1999

Functional impairment and utilization of services associated with posttraumatic stress in the community.

This study describes social functioning and service utilization patterns associated with posttraumatic stress symptoms relative to nonpsychiatric controls and depressive disorder controls in a cross-sectional epidemiological survey. Data from 49 cases and 147 controls who participated in the North Carolina component of the Epidemiologic Catchment Area study were examined. Results indicate that symptoms of posttraumatic stress were associated with impairment along several domains of functioning: social, financial, physical, and psychological. Individuals with posttraumatic stress were found to have more socioeconomic disadvantages and impaired functioning. Despite this, individuals with posttraumatic stress are receiving relatively few mental health services. Further research assessing service use, treatment, and functional outcomes are indicated.

Adolescent↗
PubMed1998

The role of Medicaid in ensuring children's access to care.

CONTEXT: Congress enacted a series of laws beginning in the mid 1980s to expand Medicaid eligibility for children, especially those in poor families. As a result, Medicaid enrollment of children has nearly doubled over the past decade. OBJECTIVE: To assess the effectiveness of Medicaid in improving access to and use of health services by poor children. DESIGN: Analysis of cross-sectional survey data from the 1995 National Health Interview Survey. Poor children with Medicaid were compared to poor children without insurance and nonpoor children with private insurance. SETTING AND PARTICIPANTS: A total of 29711 children younger than 18 years (3716 poor children with Medicaid, 1329 poor children without insurance, 14609 nonpoor children with private insurance, and 10057 children with other combinations of poverty and insurance status) included in a nationally representative stratified probability sample of the US noninstitutionalized population. MAIN OUTCOME MEASURES: Usual source of care, access to a regular clinician, unmet health needs, and use of physician services. RESULTS: Poor children with Medicaid compared to poor children without health insurance experienced superior access across all measured dimensions of health care, including presence of a usual source of care (95.6% vs 73.8%), frequency of unmet health needs (2.1 % vs 5.9%), and use of medical services (eg, > or =1 physician contact in past year) (83.9% vs 60.7%). Poor children with Medicaid compared to nonpoor children with private insurance used similar levels of physician services (83.9% vs 84%), but were more likely to have unmet health needs (2.1 % vs 0.6%) and were less likely to have a usual source of care (95.6% vs 97.4%). CONCLUSION: Medicaid is associated with improvements in access to care and use of services. However, there remains room for improvement when Medicaid is judged against private health insurance. The Balanced Budget Act of 1997 contains several Medicaid provisions that could stimulate further improvements in access for poor children.

Child↗
PubMed1998

Health insurance and access to primary care for children.

BACKGROUND: Numerous studies have demonstrated that insurance status influences the amount of ambulatory care received by children, but few have assessed the role of insurance as a determinant of children's access to primary care. We studied the effect of health insurance on children's access to primary care. METHODS: We analyzed a sample of 49,367 children under 18 years of age from the 1993-1994 National Health Interview Survey, a nationwide household survey. The overall rate of response was 86.5 percent. The survey included questions on insurance coverage and access to primary care. RESULTS: An estimated 13 percent of U.S. children did not have health insurance in 1993-1994. Uninsured children were less likely than insured children to have a usual source of care (75.9 percent vs. 96.2 percent, P<0.001). Among those with a usual source of care, uninsured children were more likely than insured children to have no regular physician (24.3 percent vs. 13.8 percent, P<0.001), to be without access to medical care after normal business hours (11.8 percent vs. 7.1 percent, P<0.001), and to have families that were dissatisfied with at least one aspect of their care (19.6 percent vs. 14.0 percent, P=0.01). Uninsured children were more likely than insured children to have gone without needed medical, dental, or other health care (22.2 percent vs. 6.1 percent, P<0.001). Uninsured children were also less likely than insured children to have had contact with a physician during the previous year (67.4 percent vs. 83.8 percent, P<0.001). All differences remained significant after we controlled for potential confounders using linear and logistic regression. CONCLUSIONS: Among children, having health insurance is strongly associated with access to primary care. The new children's health insurance program enacted as part of the Balanced Budget Act of 1997 may substantially improve access to and use of primary care by children.

Adolescent↗
PubMed1998

Mapping of the alpha-tectorin gene (TECTA) to mouse chromosome 9 and human chromosome 11: a candidate for human autosomal dominant nonsyndromic deafness.

alpha-Tectorin is one of the major noncollagenous components of the mammalian tectorial membrane in the inner ear. We have mapped the gene encoding alpha-tectorin to mouse chromosome 9 and human chromosome 11 in a known region of conserved synteny. Human YAC clones containing alpha-tectorin have been identified, demonstrating physical linkage to the anonymous marker D11S925. This places alpha-tectorin within the genetic interval that contains both the human nonsyndromic autosomal dominant deafness DFNA12 and the proximal limit of a subset of deletions within Jacobsen syndrome. Thus both DFNA12 and the hearing loss in some cases of Jacobsen syndrome may be due to haploinsufficiency for TECTA.

Animals↗
PubMed1998

Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment.

The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major non-collagenous components of the tectorial membrane. Recently, the gene encoding mouse alpha-tectorin (Tecta) was mapped to a region of mouse chromosome 9, which shows evolutionary conservation with human chromosome 11q (ref. 3), where linkage was found in two families, one Belgian (DFNA12; ref. 4) and the other, Austrian (DFNA8; unpublished data), with autosomal dominant non-syndromic hearing impairment. We determined the complete sequence and the intron-exon structure of the human TECTA gene. In both families, mutation analysis revealed missense mutations which replace conserved amino-acid residues within the zona pellucida domain of TECTA. These findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.

Alternative Splicing↗
PubMed1998

Evaluating community efforts to decategorize and integrate financing of children's health services.

Publicly funded categorical programs for children often differ in eligibility rules, allowable services, and criteria for provider participation, making it necessary for families to navigate through several programs to piece together care for their children. Recognizing these problems, the Robert Wood Johnson Foundation launched a national demonstration project in 1991 with the goal of decategorizing children's health services in nine communities. It was hoped that by releasing funds from categorical restrictions on their use, scarce public resources could be directed where they might have the greatest impact. However, the demonstration sites confronted a number of challenges in designing and implementing decategorization strategies: an absence of existing models and effective technical assistance; political hurdles in gaining cooperation from the multiple local agencies engaged in service provision; and difficulties in carrying out major programmatic changes when the health care system itself was rapidly being transformed. The proposition that decategorization holds promise as a tool for improving access to health care deserves further investigation.

Adolescent↗
PubMed1998

The use of formative evaluation to assess integrated services for children. The Robert Wood Johnson Foundation Child Health Initiative.

This article describes the use of formative evaluation in assessing the feasibility of implementing a new service integration effort. The Child Health Initiative, a nine-site, national demonstration project funded in 1991 by the Robert Wood Johnson Foundation, sought to implement systemic change through the creation of new mechanisms for spending service dollars more flexibly at the local site. The Child Health Initiative called for developing local child health-monitoring systems, a care coordination mechanism, and a program for decategorizing the myriad of restrictive categorical public programs serving children. Most demonstration communities experienced some degree of success in achieving the first two components, but none was able to implement decategorization during the 3- to 5-year funding period. Key lessons for evaluators include the need for (a) a flexible evaluation design that can sequentially adapt to changes in program implementation, (b) repeated longitudinal data collection measures to document changes over time, (c) avoidance of a premature focus on program outcomes, and (d) methods to establish attribution of outcomes.

Child↗