Biomedical subjects

Christopher Brown

Publications and source records attributed to Christopher Brown.

12 recordsLinked to original sources

PubMed2006

Characterisation of wear particles produced by metal on metal and ceramic on metal hip prostheses under standard and microseparation simulation.

The failure of metal on polyethylene total hip replacements due to wear particle induced osteolysis and late aseptic loosening has focused interest upon alternative bearings, such as metal on metal implants. A recent advance in this field has been the development of a novel ceramic on metal implant. The characteristics of the wear particles generated in this low-wearing bearing have not been previously determined. The aims of this study were to characterise metal wear particles from metal on metal and ceramic on metal hips under standard and adverse (microseparation) wear conditions. Accurate characterisation of cobalt-chrome wear particles is difficult since the reactive nature of the particles prevents them from being isolated using acids and bases. A method was developed to isolate the metal wear particles using enzymes to digest serum containing lubricants from metal on metal and ceramic on metal hip simulations. High resolution scanning electron microscopy was then used to characterise the wear particles generated by both metal on metal and ceramic on metal implants under standard and microseparation wear conditions. The wear particles isolated from all simulations had a mean size of less than 50 nm with a rounded and irregular morphology. No significant difference was found between the size of wear particles generated under any conditions.

Ceramics↗

PubMed2006

HIV and other lentiviral infections cause defects in neutrophil chemotaxis, recruitment, and cell structure: immunorestorative effects of granulocyte-macrophage colony-stimulating factor.

Patients with HIV infection exhibit deficits in bacterial and fungal clearance, and possibly depressed innate immunity. In this study, we observed that neutrophils from HIV-infected patients have a profound defect in chemotaxis in response to endogenous (IL-8) and bacterial (fMLP) chemoattractants, which was directly correlated with peripheral CD4(+) lymphocyte levels but not plasma viral load. A similar chemotactic defect was observed in the feline immunodeficiency virus (FIV) model of HIV infection. Intravital microscopy of FIV-infected animals revealed marked impairment in the in vivo recruitment of leukocytes; specifically integrin-dependent neutrophil adhesion and emigration induced by bacterial products. Treatment of FIV-infected animals with GM-CSF re-established both neutrophil recruitment (rolling, adhesion, and emigration) and in vitro chemotaxis to the levels seen in uninfected animals. This restoration of neutrophil responses was not due to GM-CSF-mediated priming. Rather, HIV and FIV infections resulted in defective neutrophil development, with an ensuing reduction in neutrophil granularity and chemotactic receptor expression. GM-CSF therapy restored neutrophil granularity, implying restoration of normal neutrophil development. Together, our findings underscore the fundamental defects in innate immunity caused by lentivirus infections, while also indicating that GM-CSF may be a potential immunorestorative therapy for HIV-infected patients.

Animals↗

PubMed2006

Cyclic peptide helices: a hybrid beta-hairpin/beta-helical supersecondary structure.

This communication describes the design and characterization of a new peptide motif that is a hybrid of beta-hairpin and beta-helical structures. This motif was supported by CD and IR spectrocopies in nonpolar organic solvents and was confirmed by NMR spectroscopy and structure calculations using NMR-derived restraints. The beta-hairpin/beta-helical motif represents a potentially attractive new structural template for a variety of possible applications in biomolecular design, such as ligands for macromolecular targets and building blocks for new protein architectures.

Models, Molecular↗

PubMed2006

Botulinum toxin injection site localization for the tibialis posterior muscle.

Thirty-one cadaveric lower limbs were dissected to identify the innervation of the tibialis posterior muscle to aid localization of the injection site for botulinum toxin for the treatment of an equinovarus deformity. A posterior midline surface-anatomy axis was defined from the level of the head of the fibula proximally to the intermalleolar axis distally. The nerve to tibialis posterior branched from the tibial trunk 13.4% down this axis and entered the muscle 22.1% along the same axis, within 1 cm of the midline. We also report the use of ultrasound for muscle localization at the level of the anatomically defined motor point.

Botulinum Toxins↗

PubMed2006

Herpes zoster--varicella complicating anterior thoracic surgery: 2 case reports.

This article reviews the reactivation of the latent varicella-zoster virus infection within the sensory dorsal root ganglia resulting in shingles. Although the association between surgery and reactivation of the varicella-zoster virus is known, we feel it is important to keep the diagnosis of shingles in mind especially in a patient with sudden onset of increased pain after surgery. Our purpose is to report 2 rare clinical presentations of shingles after spinal surgery in which the patient's initial diagnosis was not clear until the classical rash was observed. Two case reports are presented in which 1 patient developed shingles 5 days after surgery with distribution of the maculopapular rash in a surgical incision, whereas the second patient did not present until 4 weeks after surgery with a disseminated picture. Early recognition of this postoperative problem is imperative for prompt and appropriate management, as misdiagnosis can lead to short-term and long-term pain control issues, postherpetic neuralgia, neuropathic pain, or other related sequelae.

Diagnosis, Differential↗

PubMed2006

Attitudes, knowledge and practice of CRC screening among GPs in Queensland.

BACKGROUND: Colorectal cancer (CRC) is the most common invasive cancer in Australia. Randomised trials have shown that mortality from CRC can be reduced with the use of screening modalities such as faecal occult blood testing (FOBT). This study sought to determine current attitudes, knowledge and practices of general practitioners in relation to CRC screening. METHODS: A cross sectional survey of 1500 GPs in Queensland. RESULTS: Responses were received from 769 (55.6%) GPs. Fifty-three percent of GPs recommended using FOBT for asymptomatic patients over 50 years of age and 18.6% would recommend colonoscopy in such patients. Compared to a previous survey, GPs are now more likely to use FOBT (RR: 2.01, 95% CI: 1.58-2.56). Two-thirds (66.7%) would support a population based screening program using FOBT, an increase of 16% over 3 years. DISCUSSION: Current use of FOBT in asymptomatic patients, support for population based FOBT, and knowledge of the benefits of CRC screening has increased significantly from previous surveys.

Aged↗

PubMed2005

Trends in the evolution of the prodynorphin gene in teleosts: cloning of eel and tilapia prodynorphin cDNAs.

The detection of the prodynorphin gene in anuran amphibians and lungfishes may indicate that this gene arose as a result of the duplication of the proenkephalin gene early during the divergence of the Sarcopterygii, or that this gene may predate the divergence of the ray-finned fish and the lobe-finned fish. The cloning of prodynorphin-related genes from the pufferfish and zebrafish supports the latter hypothesis. This study analyzes trends in the radiation of the prodynorphin gene in teleosts. Prodynorphin cDNAs were cloned from the brain of the eel Anguilla rostrata and the Nile tilapia, Oreochromis niloticus. These teleost prodynorphin sequences have distinct alpha-neoendorphin, dynorphin A, and dynorphin B sequences, and a novel opioid sequence, YGGFI. The relationship of these teleost prodynorphin sequences to other actinopterygian and sarcopterygian prodynorphin sequences will be discussed.

Amino Acid Sequence↗

PubMed2005

Interface mutation in heptameric co-chaperonin protein 10 destabilizes subunits but not interfaces.

We here report on a human mitochondrial co-chaperonin protein 10 (cpn10) variant in which the conserved interface residue leucine-96 is replaced with glycine (Leu96Gly cpn10). According to analytical ultracentrifugation, the mutation does not perturb the ability to assemble into a heptamer and electron microscopy reveals that Leu96Gly cpn10 is ring-shaped like wild-type cpn10. Despite elimination of a hydrophobic residue, the subunit-subunit affinity is essentially identical in Leu96Gly cpn10 and in wild-type cpn10. This is explained by a compensating rearrangement in Leu96Gly cpn10, evident from cross-linking and gel-filtration experiments. As a direct result of lower monomer stability, Leu96Gly cpn10 is dramatically less stable towards chemical and thermal perturbations as compared to wild-type cpn10. We conclude that leucine-96 is an interface residue preserved to guarantee stable cpn10 monomers. Our study demonstrates that the cpn10 interfaces can adapt to structural alterations without loss of either subunit-subunit affinity or heptamer specificity.

Amino Acid Sequence↗

PubMed2005

Image transform bootstrapping and its applications to semantic scene classification.

The performance of an exemplar-based scene classification system depends largely on the size and quality of its set of training exemplars, which can be limited in practice. In addition, in nontrivial data sets, variations in scene content as well as distracting regions may exist in many testing images to prohibit good matches with the exemplars. Various boosting schemes have been proposed in machine learning, focusing on the feature space. We introduce the novel concept of image-transform bootstrapping using transforms in the image space to address such issues. In particular, three major schemes are described for exploiting this concept to augment training, testing, and both. We have successfully applied it to three applications of increasing difficulty: sunset detection, outdoor scene classification, and automatic image orientation detection. It is shown that appropriate transforms and meta-classification methods can be selected to boost performance according to the domain of the problem and the features/classifier used.

Algorithms↗

PubMed2004

Identification of minimal enhancer elements sufficient for Pax3 expression in neural crest and implication of Tead2 as a regulator of Pax3.

Pax3 is a transcription factor that is required by pre-migratory neural crest cells, which give rise to the peripheral nervous system, melanocytes, some vascular smooth muscle, and numerous other derivatives [corrected]. Both mice and humans with Pax3 deficiency exhibit neural crest-related developmental defects [corrected]. Pax3 is also expressed in the dorsal neural tube, and by myogenic progenitors in the presomitic mesoderm and the hypaxial somites. Molecular pathways that regulate Pax3 expression in the roof plate probably represent early upstream signals in neural crest induction. We have identified an enhancer region in the Pax3 genomic locus that is sufficient to recapitulate expression in neural crest precursors in transgenic mice. We show that Tead2, a member of the Tead box family of transcription factors, binds to a neural crest enhancer and activates Pax3 expression. Tead2, and its co-activator YAP65, are co-expressed with Pax3 in the dorsal neural tube, and mutation of the Tead2 binding site in the context of Pax3 transgenic constructs abolishes neural expression. In addition, a Tead2-Engrailed fusion protein is able to repress retinoic acid-induced Pax3 expression in P19 cells and in vivo. These results suggest that Tead2 is an endogenous activator of Pax3 in neural crest.

Animals↗

PubMed2003

Epidemiologic and clinical characteristics of children with newly diagnosed inflammatory bowel disease in Wisconsin: a statewide population-based study.

OBJECTIVE: To define epidemiologic and clinical characteristics of newly diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based model. STUDY DESIGN: All pediatric gastroenterologists providing care for Wisconsin children voluntarily identified all new cases of IBD during a 2-year period. Demographic and clinical data were sent to a central registry prospectively for analysis. RESULTS: The incidence of IBD in Wisconsin children was 7.05 per 100,000, whereas the incidence for Crohn's disease was 4.56, more than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred among all ethnic groups, and children from sparsely and densely populated counties were equally affected. The majority (89%) of new IBD diagnoses were nonfamilial. CONCLUSIONS: This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohn's disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.

Adolescent↗

PubMedDate not supplied

Epidural hematoma secondary to a rupture of a synovial cyst.

BACKGROUND CONTENT: With modern advances in imaging studies, synovial cysts are becoming more evident as a common component of erosive lumbar degenerative disc disease causing spinal stenosis and radiculopathy. Whereas hemorrhage can occur inside the cyst and is reported, rupture causing epidural hematoma is a rare complication and finding of this disorder. PURPOSE: To report a rare clinical presentation of a synovial cyst and spinal stenosis, where rupture of the cyst leads to an early cauda equina syndrome. STUDY DESIGN: Case report with a review of literature. METHODS: Clinical history, physical findings, and magnetic resonance imaging studies of a patient with an intraspinal synovial cyst at L4-5 1 week before a sudden worsening of symptoms are reported. RESULTS: A case report is presented of a male with a known synovial cyst at L4-5, presenting initially with neurogenic claudication. This patient developed sudden worsening of symptoms with bilateral lower extremity pain, weakness, and radiculopathy with difficult voiding. The patient had developed an epidural hematoma, secondary to rupture of a synovial cyst, documented at surgical decompression. CONCLUSIONS: Although synovial cyst associated with erosive facet and erosive degenerative disc disease are common, rupture of the cyst is not. A case report of a ruptured synovial cyst leading to an early cauda equina syndrome is presented. This case illustrates the spectrum of clinical features and presentations possible with spinal stenosis complicated by lumbar synovial cyst formation.

Aged↗