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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 19 recordsLinked to original sources
PubMed2006

Erectile dysfunction after perineal compression in young men undergoing internal fixation of femur fractures.

Erectile dysfunction (ED) following treatment for lower limb fractures is not uncommon. The mechanism is thought to be a perineal neurovascular traction injury acquired during surgery. Four young men who sustained femur fracture underwent reduction and intramedullary nail fixation. Post-operatively each presented with varying degrees of ED. Phosphodiesterase inhibitors were used in each case and sexual function returned in all. It is essential that a sexual history be taken in all patients after internal fixation of femur fractures so that treatment can be initiated early on if required. This serious complication from traction may be avoidable with careful patient positioning during traction.

Accidents, Traffic↗
PubMed2006

Overnight storage of autologous stem cell apheresis products before cryopreservation does not adversely impact early or long-term engraftment following transplantation.

To reduce costs and avoid inconvenient overtime work, our institution changed policy in September 2000 so that autologous stem cell apheresis products were stored overnight before cryopreservation rather than immediately processed. This retrospective review was conducted to evaluate the possible impact of this policy change on hematopoietic engraftment following autologous stem cell transplantation (ASCT). In total, 229 consecutive lymphoma patients who underwent a single, unpurged ASCT in Calgary between January 1995 and November 2003 were evaluated. Of these patients, 131 patients' autografts underwent immediate processing and cryopreservation before September 2000, and 98 patients' autografts underwent next-day cryopreservation after overnight storage following this date. Results of univariate and multivariate analyses demonstrated no adverse effect of overnight storage before cryopreservation on the number of days to initial engraftment of platelets or neutrophils, on the proportion of patients with low blood counts 6 months post-ASCT, or on lymphoma relapse rates or overall survival post-ASCT. These data suggest that overnight storage of the autograft before cryopreservation does not adversely affect graft viability or influence long-term disease status, and support the continued use of overnight storage of stem cells before cryopreservation as a convenient, cost reduction measure.

Adolescent↗
PubMed2006

Excess cases of prostate cancer and estimated overdiagnosis associated with PSA testing in East Anglia.

This study aimed to estimate the extent of 'overdiagnosis' of prostate cancer attributable to prostate-specific antigen (PSA) testing in the Cambridge area between 1996 and 2002. Overdiagnosis was defined conceptually as detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. Records of PSA tests in Addenbrookes Hospital were linked to prostate cancer registrations by NHS number. Differences in prostate cancer registration rates between those receiving and not receiving prediagnosis PSA tests were calculated. The proportion of men aged 40 years or over with a prediagnosis PSA test increased from 1.4 to 5.2% from 1996 to 2002. The rate of diagnosis of prostate cancer was 45% higher (rate ratios (RR)=1.45, 95% confidence intervals (CI) 1.02-2.07) in men with a history of prediagnosis PSA testing. Assuming average lead times of 5-10 years, 40-98% [corrected] of the PSA-detected cases were estimated to be overdiagnosed. In East Anglia, from 1996 to 2000, a 1.6% excess of cases was associated with PSA testing (around a quarter of the 5.3% excess incidence cases observed in East Anglia from 1996 to 2000). Further quantification of the overdiagnosis will result from continued surveillance and from linkage of incidence to testing in other hospitals.

Adult↗
PubMed2006

Reproductive isolation in a threespine stickleback hybrid zone.

In many estuarine sites, morphological and genetic differences between anadromous and freshwater threespine sticklebacks are maintained despite breeding in sympatry. Here, we investigate the maintenance of this morphological divergence in a natural hybrid zone in the River Tyne, Scotland. We provide a morphological description of the hybrid zone, and using a Bayesian MCMC approach, identified distinct anadromous and freshwater genetic clusters. Anadromous and freshwater sticklebacks breed in spatial and temporal sympatry in the lower reaches of the River Tyne. The frequency of hybrids within these sites (33%) indicates prezygotic isolation is not complete, and suggests that assortative mating is not strong. However, significant heterozygote deficit and cytonuclear disequilibrium in juveniles collected from sympatric sites confirms that barriers to gene flow exist between the morphs in the wild. In addition, we found no evidence of a directional bias in hybridisation, although hybrids with anadromous mothers were more common because anadromous females outnumbered freshwater females within the hybrid zone. We discuss the potential contribution of temporal, spatial, and sexual prezygotic barriers to the observed reproductive isolation as well as postzygotic selection against hybrid zygotes or fry.

Animals↗
PubMed2006

Genetic linkage and association analysis in type 1 von Willebrand disease: results from the Canadian type 1 VWD study.

BACKGROUND: von Willebrand disease (VWD) is the most common bleeding disorder known in humans, with type 1 VWD representing the majority of cases. Unlike the other variant forms of VWD, type 1 disease represents a complex genetic trait, influenced by both genetic and environmental factors. AIM: To evaluate the contribution of the von Willebrand factor (VWF) and ABO blood group loci to the type 1 VWD phenotype, and to assess the potential for locus heterogeneity in this condition, we have performed genetic linkage and association studies on a large, unselected type 1 VWD population. METHOD: We initially collected samples from 194 Canadian type 1 VWD families for analysis. After the exclusion of families found to have either type 2 or type 3 VWD, and pedigrees with samples from single generations, linkage and association analysis was performed on 155 type 1 VWD families. RESULTS AND CONCLUSION: The linkage study has shown a low heterogeneity LOD score of 2.13 with the proportion of families linked to the VWF gene estimated to be 0.41. Linkage was not detected to the ABO locus in this type 1 VWD population. In the family-based association test, significant association was found between the type 1 VWD phenotype, the quantitative traits, VWF:Ag, VWF:RCo, and FVIII:C and the ABO 'O' and 'A' alleles and the VWF codon 1584 variant. There was also weak association with the -1185 promoter polymorphism and VWF:Ag, VWF:RCo, and FVIII:C plasma levels. These studies provide further evidence to support the role for genetic loci other than VWF and ABO in the pathogenesis of type 1 VWD.

ABO Blood-Group System↗
PubMed2006

DNA microarray analysis for the detection of mutations in hemophilia A.

BACKGROUND: Congenital deficiency of factor (F) VIII results in the inherited X-linked bleeding disorder hemophilia A. More than 900 different mutations are reported in the hemophilia A mutation database with the largest number of mutations being single nucleotide substitutions distributed throughout the gene. Complicating the molecular characterization of this disease is the complexity of the F8 gene, the mutational heterogeneity, and technical limitations of the current mutation detection techniques. OBJECTIVE: Development of a DNA oligonucleotide microarray-based technique for F8 gene analysis to detect hemophilia A mutations. METHODS: To construct the oligonucleotide DNA microarray system: a total of 720, one base pair overlapping, 25-mer perfect match probes were designed from six exons of the F8 gene. Twenty-two different F8 gene mutations previously identified by CSGE and DNA sequence analysis were tested by using a loss-of-signal analysis approach. Differentially labeled wild type and hemophilic samples were co-hybridized to the array. Sequence alterations were detected by quantifying relative losses of test sample hybridization signals to the perfectly matched probes. RESULTS: A total of 22 different F8 mutations were tested. To test the sensitivity of the system, a blinded study was performed on 16 of the samples. F8 gene mutations can be detected with 96% efficiency with this microarray system. CONCLUSION: This proof-of-principle study has demonstrated that a F8 DNA microarray platform is an alternative gene mutation analysis approach that has a high sensitivity, and reproducibility. The methodology is, however, expensive and time consuming, and with the reduction in sequencing costs, direct sequencing is now the most cost and time efficient strategy for hemophilia A mutation analysis.

DNA Mutational Analysis↗
PubMed2006

Biological effects of clinically relevant wear particles from metal-on-metal hip prostheses.

The problems of osteolysis and late aseptic loosening associated with ultra-high molecular weight polyethylene (UHMWPE) particles has lead to a renewed interest in metal-on-metal prostheses. Wear particles generated by modern Co-Cr-on-Co-Cr prostheses are nanometre in size (range: 10-120 nm; mean: about 40 nm), an order of magnitude smaller than the size of UHMWPE known to be critical for activation of osteolytic cytokines by macrophages. Co-Cr wear particles will induce osteolytic cytokine production by human macrophages, but only at high volumetric concentrations. Unlike UHMWPE, Co-Cr particles are not inert. Co-Cr particles have the potential to release metal ions; they may be toxic to cells, induce deoxyribonucleic acid damage or cause host hypersensitivity. The nanometre size range of Co-Cr wear particles means that they may be disseminated widely in the body. The potential for metal-on-metal bearings to induce adverse effects clinically will be dependent upon the rate of wear. What constitutes a safe wear rate for modern metal-on-metal bearings is unknown. However, the wear of metal-on-metal prostheses is critically dependent upon the design and, in particular, the carbon content of the alloy, the radial clearance, and the head diameter. Thus, the potential for adverse biological reactions associated with metal-on-metal bearings can be reduced by selection of appropriately designed implants.

Chromium Alloys↗
PubMed2006

Partnered care in the Bahamas: A model of advanced healthcare delivery for developing countries.

OBJECTIVE: To assess the delivery of advanced specialized medical care using The Partnered Care Model as a means of providing affordable access to all, irrespective of ability to pay. DESIGN AND METHODS: A retrospective analysis of all persons presenting to a specialized, private, cardiac unit, The Bahamas Interventional Cardiology Center (BICC), over an 8.5-year period from March 1996 to September 2004 was conducted. The Bahamas Heart Center's Discounted Service System had been applied since inception to all patients in three groups including insured patients billed at 100% of the fee schedule of The Medical Association of the Bahamas for the procedures performed, private self-pay and government patients billed at 75% and 50% respectively. Their respective distribution and contributions to total revenue was analyzed. A series of financial models were constructed taking into consideration variables that could influence the percentages of revenues collected from each sector and the number of individuals served RESULTS: One thousand five-hundred and forty-two patients received services in BICC over the 8.5 year period (56% males and 44% females age range: 0.25 - 96 years, with mean age of 55.7 years). One thousand eight-hundred and eighty-eight patient-procedures were performed, with 51% insured generating 69% total revenue, 18% Private producing 16% Revenue, and 31% Government patients generating 15%. Financial models were created to predict revenue behaviour in various scenarios. CONCLUSION: Partnered Care is a viable alternative for Governments (Ministries of Health) of developing countries to provide costly specialized healthcare to their populations at minimal expense and capital outlay. Partnered Care reduces the otherwise overwhelming burden of healthcare cost to governments, particularly in developing countries, by sharing the burden of care between the private, user and government sectors.

Bahamas↗
PubMed2006

Two clusters of human infection with influenza A/H5N1 virus in the Republic of Azerbaijan, February-March 2006.

Following the appearance of influenza A/H5 virus infection in several wild and domestic bird species in the Republic of Azerbaijan in February 2006, two clusters of potential human avian influenza due to A/H5N1 (HAI) cases were detected and reported by the Ministry of Health (MoH) to the World Health Organization (WHO) Regional Office for Europe during the first two weeks of March 2006. On 15 March 2006, WHO led an international team, including infection control, clinical management, epidemiology, laboratory, and communications experts, to support the MoH in investigation and response activities. As a result of active surveillance, 22 individuals, including six deaths, were evaluated for HAI and associated risk infections in six districts. The investigations revealed eight cases with influenza A/H5N1 virus infection confirmed by a WHO Collaborating Centre for Influenza and one probable case for which samples were not available. The cases were in two unrelated clusters in Salyan (seven laboratory confirmed cases, including four deaths) and Tarter districts (one confirmed case and one probable case, both fatal). Close contact with and de-feathering of infected wild swans was considered to be the most plausible source of exposure to influenza A/H5N1 virus in the Salyan cluster, although difficulties in eliciting information were encountered during the investigation, because of the illegality of some of the activities that might have led to the exposures (hunting and trading in wild birds and their products). These cases constitute the first outbreak worldwide where wild birds were the most likely source of influenza A/H5N1 virus infection in humans. The rapid mobilisation of resources to contain the spread of influenza A/H5 in the two districts was achieved through collaboration between the MoH, WHO and its international partners. Control activities were supported by the establishment of a field laboratory with real-time polymerase chain reaction (RT-PCR) capacity to detect influenza A/H5 virus. Daily door-to-door surveillance undertaken in the two affected districts made it unlikely that human cases of influenza A/H5N1 virus infection remained undetected.

Azerbaijan↗
PubMed2005

Experimental benchmark for an improved simulation of absolute soft-x-ray emission from polystyrene targets irradiated with the Nike laser.

Absolutely calibrated, time-resolved spectral intensity measurements of soft-x-ray emission (hnu approximately 0.1-1.0 keV) from laser-irradiated polystyrene targets are compared to radiation-hydrodynamic simulations that include our new postprocessor, Virtual Spectro. This new capability allows a unified, detailed treatment of atomic physics and radiative transfer in nonlocal thermodynamic equilibrium conditions for simple spectra from low-Z materials as well as complex spectra from high-Z materials. The excellent agreement (within a factor of approximately 1.5) demonstrates the powerful predictive capability of the codes for the complex conditions in the ablating plasma. A comparison to data with high spectral resolution (E/deltaE approximately 1000) emphasizes the importance of including radiation coupling in the quantitative simulation of emission spectra.

Journal Article↗
PubMed2005

Autologous transplantation for primary systemic AL amyloidosis is feasible outside a major amyloidosis referral centre: the Calgary BMT Program experience.

Recent reports from large amyloidosis referral centers suggest that primary systemic AL amyloidosis patients treated with high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT) survive longer than historical controls treated with less intensive chemotherapy, despite high transplant-related mortality (TRM) rates of >10%. A retrospective review was conducted to determine if the outcome of ASCT for AL amyloidosis at our institution was similar to that reported at major amyloidosis referral centers. Over a 7 year period, we treated a total of 15 AL amyloidosis patients with ASCT, including four with poor prognosis cardiac or multisystem involvement. No TRM was observed. Overall, 10 patients (67%) achieved a complete hematological response and four patients (27%) achieved a complete organ response. The 4-year event-free and overall survival rates were 60% (95% CI 32-89%) and 75% (95% CI 50-100%), respectively. One patient, who presented with cardiac failure and multiorgan involvement with colonic bleeding currently remains in complete remission 62 months post-ASCT. In conclusion, ASCT for primary AL amyloidosis can safely be performed at experienced transplant centers that are not associated with major amyloidosis referral centers, and is feasible for patients who have multisystem involvement, particularly for motivated patients with good performance status.

Adult↗
PubMed2005

Pelvic floor muscle functioning in women with vulvar vestibulitis syndrome.

Vaginal sEMG biofeedback and pelvic floor physical therapists' manual techniques are being increasingly included in the treatment of vulvar vestibulitis syndrome (VVS). Successful treatment outcomes have generated hypotheses concerning the role of pelvic floor pathology in the etiology of VVS. However, no data on pelvic floor functioning in women with VVS compared to controls are available. Twenty-nine women with VVS were matched to 29 women with no pain with intercourse. Two independent, structured pelvic floor examinations were carried out by physical therapists blind to the diagnostic status of the participants. Results indicated that therapists reached almost perfect agreement in their diagnosis of pelvic floor pathology. A series of significant correlations demonstrated the reliability of assessment results across muscle palpation sites. Women with VVS demonstrated significantly more vaginal hypertonicity, lack of vaginal muscle strength, and restriction of the vaginal opening, compared to women with no pain with intercourse. Anal palpation could not confirm generalized hypertonicity of the pelvic floor. We suggest that pelvic floor pathology in women with VVS is reactive in nature and elicited with palpations that result in VVS-type pain. Treatment interventions need to recognize the critical importance of addressing the conditioned, protective muscle guarding response in women with VVS.

Adult↗
PubMed2005

A prospective study comparing conventional methods against a structured method of gaining patients' informed consent for tonsillectomy.

OBJECTIVE: By providing junior members of medical staff with appropriate guidelines one can achieve an improved standard of informed consent for tonsillectomy, than is provided at present. DESIGN: A prospective study of 138 consecutive patients. SETTING: District General Hospital. PARTICIPANTS: A total of 138 patients undergoing routine tonsillectomy split into two groups. Group A (n=87), the conventional group, gave consent in our unit's standard manner to various grades of doctors by using a hospital general surgical consent form. Most gave their consent as outpatients, while some consented on admission. Group B (n=51), the structured consent group, gave their consent in pre-admission clinic, to an SHO using a standardized tonsillectomy consent form and a structured interview technique. MAIN OUTCOME MEASURES: A preoperative questionnaire regarding the knowledge of tonsillectomy. RESULTS: Improvement of the awareness of the risks involved with tonsillectomy was achieved by the structured consent Group B; 82% of Group A were aware of postoperative pain compared with 94% of group B (P=0.04); 63% of group A were aware of infection compared with 82% of group B (P=0.02); 100% of group B had read the consent form before signing compared with 80% of group A (P<0.01). There was no statistical difference in the awareness of postoperative haemorrhage (91 versus 98%, P=0.15). CONCLUSION: By providing junior medical staff with guidelines, senior staff retain responsibility for consent while improving the standard of informed consent for tonsillectomy.

Adolescent↗
PubMed2005

A new HLA-A allele, HLA-A*6824, identified in three unrelated individuals.

A novel allele, human leukocyte antigen (HLA)-A*6824, has been identified in three unrelated individuals of northwestern European origin in a period of less than 4 months, implying that this allele may be quite common in this population. HLA-A*6824 differs from A*680102 by a single nucleotide change at position 275 in exon 2, which results in a conservative amino acid substitution from lysine to arginine in the peptide-binding groove at codon 68.

Adult↗
PubMed2005

Triage criteria in genitourinary medicine.

An audit of triage was conducted between June and September 2003 in a district general hospital genitourinary medicine department to evaluate the appropriateness of triage criteria to identify those who require urgent intervention. We selected gonorrhoea (B1), chlamydia (C4a), gential herpes (C10a/b) and epidemiological treatment of contacts of B1 or C4a (C4e/B4) as conditions requiring urgent intervention. Eighty-eight percent met one or more of the criteria and were offered urgent appointments and 69% who did not meet the criteria were offered routine appointments. The incidences of B1, C4a, C10a/b and C4e/B4 were 26.5%, 21.2%, 16.8% and 8% respectively in the urgent group compared with corresponding incidences of 4.4% and 16.2% respectively in the routine group. No cases of C10a/b or C4e/B4 were seen in the latter group. Although triage criteria did not identify asymptomatic infections, efficient contact tracing will improve detection of asymptomatic carriers of infections and should be encouraged. The outcome of the audit informed modifications to the criteria and reinforced the need for staff training in triage. In the United Kingdom, genitourinary medicine must be urgently prioritized and invested in, to improve access to all who need to be seen within 48 h of contacting the service.

Adult↗
PubMed2005

In situ DMSO hydration measurements of HTS compound libraries.

Compounds used in high throughput screening (HTS) are typically dissolved in DMSO. These solutions are stored automation-friendly racks of wells or tubes. DMSO is hygroscopic and quickly absorbs water from the atmosphere. When present in DMSO compound solutions, water can accelerate degradation and precipitation. Understanding DMSO hydration in an HTS compound library can improve storage and screening methods by managing the impact of water on compound stability. A non-destructive, acoustic method compatible with HTS has been developed to measure water content in DMSO solutions. Performance of this acoustic method was compared with an optical technique and found to be in good agreement. The accuracy and precision of acoustic measurements was shown to be under 3% over the tested range of DMSO solutions (0% to 35% water by volume) and insensitive to the presence of HTS compounds at typical storage concentrations. Time course studies of hydration for wells in 384-well and 1536-well microplates were performed. Well geometry, fluid volume, well position and atmospheric conditions were all factors in hydration rate. High rates of hydration were seen in lower-volume fills, higher-density multi-well plates and when there was a large differential between the humidity of the lab and the water content of the DMSO. For example, a 1536-well microplate filled with 2microL of 100% DMSO exposed for one hour to a laboratory environment with approximately 40% relative humidity will absorb over 6% water by volume. Understanding DMSO hydration rates as well as the ability to reverse library hydration are important steps towards managing stability and availability of compound libraries.

Acoustics↗