Biomedical subjects

M Dunn

Publications and source records attributed to M Dunn.

At least 19 recordsLinked to original sources

PubMed2007

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis.

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.

Adult↗

PubMed2006

The DNA sequence and biological annotation of human chromosome 1.

The reference sequence for each human chromosome provides the framework for understanding genome function, variation and evolution. Here we report the finished sequence and biological annotation of human chromosome 1. Chromosome 1 is gene-dense, with 3,141 genes and 991 pseudogenes, and many coding sequences overlap. Rearrangements and mutations of chromosome 1 are prevalent in cancer and many other diseases. Patterns of sequence variation reveal signals of recent selection in specific genes that may contribute to human fitness, and also in regions where no function is evident. Fine-scale recombination occurs in hotspots of varying intensity along the sequence, and is enriched near genes. These and other studies of human biology and disease encoded within chromosome 1 are made possible with the highly accurate annotated sequence, as part of the completed set of chromosome sequences that comprise the reference human genome.

Base Sequence↗

PubMed2006

National survey of doses from CT in the UK: 2003.

A review of patient doses from CT examinations in the UK for 2003 has been conducted on the basis of data received from over a quarter of all UK scanners, of which 37% had multislice capability. Questionnaires were employed to collect scan details both for the standard protocols established at each scanner for 12 common types of CT examination on adults and children, and for samples of individual patients. This information was combined with published scanner-specific CT dose index (CTDI) coefficients to estimate values of the standard dose indices CTDI(w) and CTDI(vol) for each scan sequence. Knowledge of each scan length allowed assessment of the dose-length product (DLP) for each examination, from which effective doses were then estimated. When compared with a previous UK survey for 1991, wide variations were still apparent between CT centres in the doses for standard protocols. The mean UK doses for adult patients were in general lower by up to 50% than those for 1991, although doses were slightly higher for multislice (4+) (MSCT) relative to single slice (SSCT) scanners. Values of CTDI(vol) for MSCT were broadly similar to European survey data for 2001. The third quartile values of these dose distributions have been used to derive UK national reference doses for examinations on adults (separately for SSCT and MSCT) and children as initial tools for promoting patient protection. The survey has established the PREDICT (Patient Radiation Exposure and Dose in CT) database as a sustainable national resource for monitoring dose trends in CT through the ongoing collation of further survey data.

Adult↗

PubMed2006

The effects of vitamin C supplementation on symptoms of delayed onset muscle soreness.

AIM: The aim of this study was to compare the effects of 8 days of vitamin C (VC) supplementation on elbow flexor delayed onset muscle soreness (DOMS) to 8 days of placebo ingestion. METHODS: For 3 days prior to an exercise bout (2 x 20 eccentric elbow extensions), and for 5 days after, a treatment group ingested 3 x 1000 mg/day of VC versus 3 x 50 mg/day of glucose ingestion for the placebo group over the same time period. All subjects were prescreened via dietary recall to exclude any subjects with habitual VC consumption greater than 400 mg/day. Subject comprised 24 subjects (male and female) randomly divided into 2 groups of 12 subjects. Treatment group comprised 5 females and placebo group comprised 8 females. RESULTS: Data from a repeated measures ANOVA indicate that DOMS was successfully induced in both groups via significant time effects for strength loss (P = 0.0001), point tenderness (P = 0.0001), elbow flexor decreased range of motion (P = 0.013), and subjective pain (P = 0.0001). However, there were no significant between group differences in response to any of the aforementioned variables: strength loss (P = 0.202), point tenderness (P = 0.824), elbow flexor range of motion (P = 0.208), subjective pain (P = 0.342). CONCLUSIONS: The results of this study suggest that a VC supplementation protocol of 3 x 1000 mg/day for 8 days is ineffective in protecting against selected markers of DOMS.

Adult↗

PubMed2004

The DNA sequence and comparative analysis of human chromosome 10.

The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.

Animals↗

PubMed2004

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗

PubMed2004

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Chromosome Mapping↗

PubMed2003

The DNA sequence and analysis of human chromosome 6.

Chromosome 6 is a metacentric chromosome that constitutes about 6% of the human genome. The finished sequence comprises 166,880,988 base pairs, representing the largest chromosome sequenced so far. The entire sequence has been subjected to high-quality manual annotation, resulting in the evidence-supported identification of 1,557 genes and 633 pseudogenes. Here we report that at least 96% of the protein-coding genes have been identified, as assessed by multi-species comparative sequence analysis, and provide evidence for the presence of further, otherwise unsupported exons/genes. Among these are genes directly implicated in cancer, schizophrenia, autoimmunity and many other diseases. Chromosome 6 harbours the largest transfer RNA gene cluster in the genome; we show that this cluster co-localizes with a region of high transcriptional activity. Within the essential immune loci of the major histocompatibility complex, we find HLA-B to be the most polymorphic gene on chromosome 6 and in the human genome.

Animals↗

PubMed2003

Reef-coral proteins as visual, non-destructive reporters for plant transformation.

Recently, five novel fluorescent proteins have been isolated from non-bioluminescent species of reef-coral organisms and have been made available through ClonTech. They are AmCyan, AsRed, DsRed, ZsGreen and ZsYellow. These proteins are valuable as reporters for transformation because they do not require a substrate or external co-factor to emit fluorescence and can be tested in vivo without destruction of the tissue under study. We have evaluated them in a large range of plants, both monocots and dicots, and our results indicate that they are valuable reporting tools for transformation in a wide variety of crops. We report here their successful expression in wheat, maize, barley, rice, banana, onion, soybean, cotton, tobacco, potato and tomato. Transient expression could be observed as early as 24 h after DNA delivery in some cases, allowing for very clear visualization of individually transformed cells. Stable transgenic events were generated, using mannose, kanamycin or hygromycin selection. Transgenic plants were phenotypically normal, showing a wide range of fluorescence levels, and were fertile. Expression of AmCyan, ZsGreen and AsRed was visible in maize T1 seeds, allowing visual segregation to more than 99% accuracy. The excitation and emission wavelengths of some of these proteins are significantly different; the difference is enough for the simultaneous visualization of cells transformed with more than one of the fluorescent proteins. These proteins will become useful tools for transformation optimization and other studies. The wide variety of plants successfully tested demonstrates that these proteins will potentially find broad use in plant biology.

Anthozoa↗

PubMed2001

Spatiotemporal maturation of the central and lateral N1 components to tones.

This paper examines maturational changes in the spatiotemporal features of central and lateral N1 components of the auditory evoked potentials (AEPs) to tone stimuli presented with a long stimulus onset asyncrony (SOA; 4200 ms) using the scalp current density (SCD) technique. A group of typically developing children ranging from 6 to 12 years of age and a group of adults were studied. Recently studies have begun to explore the topography of these components in children. These studies, however, often used rapidly presented stimuli and did not elicit observable central N1s in the younger children. Our stimuli elicited both central and lateral N1s. Peak latencies of both components decreased with age. Peak amplitude also decreased with age for the lateral N1 but not for the central N1. Consequently, the difference between the lateral N1 and the central N1 amplitudes (or the ratio of lateral N1 amplitude to central N1 amplitude) also decreased with age, dramatically altering the morphology of the elicited AEP waveforms. Topography of the lateral N1 did not change with age. The location of maximal activation for the central N1 appeared to move more medially with age but this 'apparent' movement is probably due to the decreasing impact of the partially overlapping lateral N1 component whose amplitude is significantly smaller in adults than in children.

Acoustic Stimulation↗

PubMed2001

Autistic disorder versus other pervasive developmental disorders in young children: same or different?

Eighteen preschool children diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders Third Edition Revised (DSM III-R) as having Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) were compared to 176 children with DSM III-R Autistic Disorder (AD), and to 311 non-autistic children with developmental language disorders (DLD) (N = 201) or low IQ (N = 110). All children were partitioned into "high" and "low" cognitive subgroups at a nonverbal IQ of 80. Within cognitive subgroups, the 18 PDD-NOS children did not differ significantly from either the DLD or the AD children in verbal and adaptive skills and obtained scores intermediate between those of these groups. The PDD-NOS did not differ from the AD children in maladaptive behaviors. Both the PDD-NOS and AD children had many more of these behaviors than the non-autistic comparison groups. Children in the "high" and "low" cognitive subgroups of AD, but not of PDD-NOS, differed substantially on most measures, with the children with lower cognitive scores significantly more impaired on all measures. Similarity of PDD-NOS children to AD children in maladaptive behaviors and an intermediate position between autistic and non-autistic groups on virtually all measures explains the difficulty clinicians encounter in classifying children with PDD and raises questions about the specificity of these diagnostic subtypes of the autistic spectrum.

Autistic Disorder↗

PubMed2001

Effects of Buddleja globosa leaf and its constituents relevant to wound healing.

An aqueous extract of Buddleja globosa leaves, used traditionally in Chile for wound healing, was tested for the ability to stimulate growth of fibroblasts in vitro and for antioxidant activity in the same fibroblast cell system challenged with hydrogen peroxide. Low concentrations of the extract gave an increase in fibroblast growth which was not statistically significant but cytotoxicity was observed at concentrations greater than 50 microg/ml. The extract showed strong antioxidant effect and fractionation led to the isolation of three flavonoids and two caffeic acid derivatives, each of which was shown to contribute to the antioxidant effect at concentrations below 10 microg/ml. These activities would accelerate the healing of wounds.

Antioxidants↗

PubMed2001

Predictors and correlates of adaptive functioning in children with developmental disorders.

Autism is a developmental disorder marked by impairments in socialization, communication, and perseverative behavior and is associated with cognitive impairment and deficits in adaptive functioning. Research has consistently demonstrated that children with autism have deficits in adaptive functioning more severe than their cognitive deficits. This study investigates the correlates and predictors of adaptive functioning as measured by the Vineland Adaptive Behavior Scales in high- and low-functioning children with autism and their age and nonverbal IQ matched controls. Thirty-five 9-year-old children with high-functioning autism (HAD) were compared with 31 age-matched children with developmental language disorder (DLD), and 40 9-year-old children with low-functioning autism (LAD) were compared with 17 age-matched children with low IQ on adaptive functioning, IQ, autistic symptomology, and tests of language and verbal memory. Results indicate that both groups with autism were significantly impaired compared to their matched controls on Socialization and Daily Living, but not Communication and that these impairments were more pronounced in the HAD group than in the LAD group. Adaptive behavior was strongly correlated with autistic symptomology only in the HAD group. Regression analyses indicated that IQ was strongly predictive of adaptive behavior in both low-functioning groups, but tests of language and verbal memory predicted adaptive behavior in the higher functioning groups. Results suggest that IQ may act as a limiting factor for lower functioning children but higher functioning children are impaired by specific deficits, including autistic symptomology and impaired language and verbal memory.

Adaptation, Psychological↗

PubMed2001

Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences.

A key cause of respiratory distress syndrome (RDS) in the prematurely born infant is deficiency of pulmonary surfactant, a lipoprotein complex. Both low levels of surfactant protein A (SP-A) and SP-A alleles have been associated with RDS. Using the candidate gene approach, we performed family-based linkage studies to discern linkage of SP-A to RDS and identify SP-A susceptibility or protective alleles. Moreover, we performed case-control studies of whites and blacks to detect association between RDS and SP-A alleles. Transmission disequilibrium test (TDT) analysis revealed that the frequency of transmission (from parent to the offspring with RDS) of alleles 6A(2) and 1A(0) and of 1A(0)/6A(2) haplotype in RDS was increased, whereas transmission of alleles 1A(5) and 6A(4) and of haplotype 1A(5)/6A(4) was decreased. Extended TDT analysis further strengthened the observations made. The case-control studies showed that in whites or blacks with RDS the frequencies of specific genotypes, 1A(0) and 6A(2) or 1A(0), were increased, respectively, but the frequency of specific 6A(3) genotypes was increased in certain white subgroups and decreased in blacks. Regression analysis revealed gestational age (GA) and 6A(3) genotypes are significant factors in blacks with RDS. In whites with RDS, GA and antenatal steroids are important factors. The data together indicate linkage between SP-A and RDS; certain SP-A alleles/haplotypes are susceptibility (1A(0), 6A(2), 1A(0)/6A(2)) or protective (1A(5), 6A(4), 1A(5)/6A(4)) factors for RDS. Some differences between blacks and whites with regard to SP-A alleles may exist.

Alleles↗

PubMed2001

Spindle dynamics and the role of gamma-tubulin in early Caenorhabditis elegans embryos.

gamma-Tubulin is a ubiquitous and highly conserved component of centrosomes in eukaryotic cells. Genetic and biochemical studies have demonstrated that gamma-tubulin functions as part of a complex to nucleate microtubule polymerization from centrosomes. We show that, as in other organisms, Caenorhabditis elegans gamma-tubulin is concentrated in centrosomes. To study centrosome dynamics in embryos, we generated transgenic worms that express GFP::gamma-tubulin or GFP::beta-tubulin in the maternal germ line and early embryos. Multiphoton microscopy of embryos produced by these worms revealed the time course of daughter centrosome appearance and growth and the differential behavior of centrosomes destined for germ line and somatic blastomeres. To study the role of gamma-tubulin in nucleation and organization of spindle microtubules, we used RNA interference (RNAi) to deplete C. elegans embryos of gamma-tubulin. gamma-Tubulin (RNAi) embryos failed in chromosome segregation, but surprisingly, they contained extensive microtubule arrays. Moderately affected embryos contained bipolar spindles with dense and long astral microtubule arrays but with poorly organized kinetochore and interpolar microtubules. Severely affected embryos contained collapsed spindles with numerous long astral microtubules. Our results suggest that gamma-tubulin is not absolutely required for microtubule nucleation in C. elegans but is required for the normal organization and function of kinetochore and interpolar microtubules.

Amino Acid Sequence↗

PubMed2001

Executive functioning in high-functioning children with autism.

Executive functioning was investigated in 34 children (24 boys and 10 girls) with developmental language disorder (DLD) and 21 children (18 boys and 3 girls) with high-functioning autistic disorder (HAD) matched on Full Scale IQ, Nonverbal IQ, age (mean age 9 year, 1 month), and SES. The DLD group had a Verbal IQ that was 10 points higher than the HAD group. These children were given the Wisconsin Card Sorting Test (WCST), the Mazes subtest from the WISC-R, the Underlining test, and the Rapid Automatized Naming test. In addition, these children were given the Vineland Scales of Adaptive Functioning and the Wing Diagnostic Symptom Checklist in order to assess severity of autistic symptomatology. Results indicated that the only significant difference between the two groups on the cognitive tasks was perseverative errors on the WCST; there was no significant difference on total number of categories achieved or total number of errors on the WCST or on the other executive function measures. There was also significant overlap in the scores between the two groups and the difference in perseverative errors was no longer significant when Verbal IQ was partialled out. Executive functioning was strongly related to all IQ variables in the DLD group and particularly related to Verbal IQ in the HAD group. Although there was a relationship in the HAD group between executive functioning and adaptive functioning, as well as between executive functioning and autistic symptomatology, these relationships were generally no longer significant in the HAD group after the variance due to Verbal IQ was accounted for. The results are interpreted to indicate that although impaired executive functioning is a commonly associated feature of autism, it is not universal in autism and is unlikely to cause autistic behaviors or deficits in adaptive function.

Autistic Disorder↗

PubMed2001

Prospective randomized trial comparing shock wave lithotripsy and ureteroscopy for management of distal ureteral calculi.

PURPOSE: We compared the efficacy of shock wave lithotripsy and ureteroscopy for treatment of distal ureteral calculi. MATERIALS AND METHODS: A total of 64 patients with solitary, radiopaque distal ureteral calculi 15 mm. or less in largest diameter were randomized to treatment with shock wave lithotripsy (32) using an HM3 lithotriptor (Dornier MedTech, Kennesaw, Georgia) or ureteroscopy (32). Patient and stone characteristics, treatment parameters, clinical outcomes, patient satisfaction and cost were assessed for each group. RESULTS: The 2 groups were comparable in regard to patient age, sex, body mass index, stone size, degree of hydronephrosis and time to treatment. Procedural and operating room times were statistically significantly shorter for the shock wave lithotripsy compared to the ureteroscopy group (34 and 72 versus 65 and 97 minutes, respectively). In addition, 94% of patients who underwent shock wave lithotripsy versus 75% who underwent ureteroscopy were discharged home the day of procedure. At a mean followup of 21 and 24 days for shock wave lithotripsy and ureteroscopy, respectively, 91% of patients in each group had undergone imaging with a plain abdominal radiograph, and all studies showed resolution of the target stone. Minor complications occurred in 9% and 25% of the shock wave lithotripsy and ureteroscopy groups, respectively (p value was not significant). No ureteral perforation or stricture occurred in the ureteroscopy group. Postoperative flank pain and dysuria were more severe in the ureteroscopy than shock wave lithotripsy group, although the differences were not statistically significant. Patient satisfaction was high, including 94% for shock wave lithotripsy and 87% for ureteroscopy (p value not significant). Cost favored ureteroscopy by $1,255 if outpatient treatment for both modalities was assumed. CONCLUSIONS: Ureteroscopy and shock wave lithotripsy were associated with high success and low complication rates. However, shock wave lithotripsy required significantly less operating time, was more often performed on an outpatient basis, and showed a trend towards less flank pain and dysuria, fewer complications and quicker convalescence. Patient satisfaction was uniformly high in both groups. Although ureteroscopy and shock wave lithotripsy are highly effective for treatment of distal ureteral stones, we believe that HM3 shock wave lithotripsy, albeit slightly more costly, is preferable to manipulation with ureteroscopy since it is equally efficacious, more efficient and less morbid.

Adult↗

PubMed2001

Complications of laparoscopic procedures after concentrated training in urological laparoscopy.

PURPOSE: To increase the safety and efficiency of laparoscopic surgery clinical training programs have been developed to increase the skill and efficiency of urological trainees. We evaluated the impact of dedicated laparoscopy training on the rate and type of complications after trainees entered clinical practice. MATERIALS AND METHODS: Data were obtained from 13 centers where laparoscopy was performed by a single surgeon with at least 12 months of training in urological laparoscopy before clinical practice. Data included training experience, laparoscopic procedures performed after commencing clinical practice and associated complications. Procedures were classified as easy, moderate and difficult. RESULTS: During training each surgeon participated in a mean of 71 cases. In clinical practice a total of 738 laparoscopic cases were performed with the group reporting an overall complication rate of 11.9%. The rate was unchanged when the initial 20, 30 and 40 cases per surgeon were compared with all subsequent cases (12%, 11.9% and 12% versus 11.8 to 12%, respectively). The re-intervention rate was 1.1%. The complication rate increased with case difficulty. Overall and early complication rates attributable to laparoscopic technique in the initial 20, 30 and 40 cases were identical. The most common complications were neuropathy in 13 patients, urine leakage/urinoma in 9, transfusion in 7 and ileus in 5. CONCLUSIONS: The complication rate of surgeons who completed at least 12 months of laparoscopy training did not differ according to initial versus subsequent surgical experience. Intensive training seems to decrease the impact of the learning curve for laparoscopy.

Humans↗