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Biomedical subjects

N Bishop

Publications and source records attributed to N Bishop.

At least 19 recordsLinked to original sources
PubMed2006

Migration and cyclic motion of a new short-stemmed hip prosthesis--a biomechanical in vitro study.

BACKGROUND: Uncemented, short-stemmed hip prostheses have been developed to reduce the risk of stress shielding and to preserve femural bone stock. The long-term success of these implants is yet uncertain. Prerequisite for osseointegration is sufficient primary stability. In this study the cyclic motion and migration patterns of a new short-stemmed hip implant were compared with those for two clinically successful shaft prostheses. METHODS: The prostheses were implanted in paired fresh human femura and loaded dynamically (gait cycle) with increasing load (max 2,100 N) up to 15,000 cycles. Relative displacements between prosthesis and bone were recorded using a 3D-video analysis system. FINDINGS: The short stem displayed a biphasic migration pattern with stabilisation at maximum load. Initial migration was predominantly into varus and was greater than that for the shaft prostheses. Failure occurred in cases of poor bone quality and malpositioning. Cyclic motion of the short prosthesis was less than that for the shaft prostheses. Surface finish showed no effect. System stiffness for the new stem was lower than for the shaft prostheses. INTERPRETATION: The new stem tended to migrate initially more than the shaft prostheses, but stabilised when cortical contact was achieved or the cancellous bone was compacted sufficiently. Bone quality and correct positioning were important factors for the short stem. The lower cyclic motion of the new stem should be favourable for bony ingrowth. The lower system bending stiffness with the new implant indicated a more physiological loading of the bone and should thereby reduce the effects of stress shielding.

Adult↗
PubMed2006

Biomechanical, morphological, and histological analysis of early failures in hip resurfacing arthroplasty.

The present revival of hip resurfacing arthroplasty may be related to an increase in early failures owing to the challenging technique of the procedure. Fifty-five retrieved implants were analysed with respect to wear, cement mantle and cement penetration, fracture and head morphology, as well as standard histology. Femoral neck fractures occurred in median after 102 days. The time to failure was shorter for older women. Major deviations from the suggested cement mantle thickness and cement penetration were found. Indications for high trauma during implantation leading to early failure due to weakening of the femoral neck were also observed. Some failures had signs of pseudarthrosis beneath the implant. Four different fracture patterns with different mean survival times were identified. Observed wear was minor with the exception of that due to alignment mistakes (rim loading). The cups were not damaged by the failures. Histological results indicate that avascular necrosis is not necessarily connected with this kind of endoprosthetic surgery. Most of the failures analysed can probably be attributed to the 'learning curve' effect, which is an unsatisfactory situation.

Aged↗
PubMed2005

Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment.

BACKGROUND: Osteopetrosis, a genetic disease characterised by osteoclast failure, is classified into three forms: infantile malignant autosomal recessive osteopetrosis (ARO), intermediate autosomal recessive osteopetrosis (IRO), and autosomal dominant osteopetrosis (ADO). METHODS: We studied 49 patients, 21 with ARO, one with IRO, and 27 with type II ADO (ADO II). RESULTS: Most ARO patients bore known or novel (one case) ATP6i (TCIRG1) gene mutations. Six ADO II patients had no mutations in ClCN7, the only so far recognised gene implicated, suggesting involvement of yet unknown genes. Identical ClCN7 mutations produced differing phenotypes with variable degrees of severity. In ADO II, serum tartrate resistant acid phosphatase was always elevated. Bone alkaline phosphatase (BALP) was generally low, but osteocalcin was high, suggesting perturbed osteoblast differentiation or function. In contrast, BALP was high in ARO patients. Elevated osteoclast surface/bone surface was noted in biopsies from most ARO patients. Cases with high osteoclasts also showed increased osteoblast surface/bone surface. ARO osteoclasts were morphologically normal, with unaltered formation rates, intracellular pH handling, and response to acidification. Their resorption activity was greatly reduced, but not abolished. In control osteoclasts, all resorption activity was abolished by combined inhibition of proton pumping and sodium/proton antiport. CONCLUSIONS: These findings provide a rationale for novel therapies targeting pH handling mechanisms in osteoclasts and their microenvironment.

Adolescent↗
PubMed2004

Performance of focus ELISA tests for herpes simplex virus type 1 (HSV-1) and HSV-2 antibodies among women in ten diverse geographical locations.

To determine the sensitivity and specificity of Focus HerpeSelect ELISAs, sera or plasma samples from women aged 18-55 years were collected in ten cities from eight countries and tested by HerpeSelect HSV-1 ELISA (Focus-HSV-1) and by HerpeSelect HSV-2 ELISA (Focus-HSV-2). Sera with Focus-HSV-2-positive results were retested; 94% of the 3617 samples retested were positive. A subset of sera from each site was then selected, based on the HSV-2 results, and tested by Western blot (WB). The sensitivity and specificity were determined with samples from ten sites (n = 967) for Focus-HSV-1 and from seven sites (n = 675) for Focus-HSV-2. Focus-HSV-1 and WB results were concordant (both negative or both positive) for 97% of samples, with 99% sensitivity and 77% specificity. Specimens from Songkla, Thailand had 84% concordance with WB results for HSV-1, while three other sites had 100% concordance. Concordance of Focus-HSV-2 and WB was 92%, with 97% sensitivity and 89% specificity. Ibadan, Nigeria had 78% concordance. Focus-HSV-2 sensitivity and specificity in sites other than Ibadan were 97% and 93%, respectively. Raising the positive cut-off index value for HSV-2 from 1.1 to 3.5 yielded a sensitivity of 90% and a specificity of 96%. A sensitivity of 90% and a specificity of 98% were achieved for sites other than Nigeria with the higher cut-off. In summary, the sensitivity and specificity of the Focus-HSV-1 and Focus-HSV-2 tests varied by site. Performance data generated in one area may not be applicable to other populations.

Adolescent↗
PubMed2003

Children and the risk of fractures caused by oral corticosteroids.

Oral corticosteroids are known to increase the risk of fracture in adults, but their effects in children remain uncertain. The medical records of general practitioners in the United Kingdom (from the General Practice Research Database) were used to estimate the incidence rates of fracture of children ages 4-17 years taking oral corticosteroids (n = 37,562) and of control children taking nonsystemic corticosteroids (n = 345,748). Each child with a fracture (n = 22,846) was subsequently matched by age, sex, practice, and calendar time to one child without a fracture. The average duration of treatment was 6.4 days (median, 5 days). The risk of fracture was increased in children with a history of frequent use of oral corticosteroids; children who received four or more courses of oral corticosteroids had an adjusted odds ratio (OR) for fracture of 1.32 (95% CI, 1.03-1.69). Of the various fracture types, the risk of humerus fracture was doubled in children who received four or more courses of oral corticosteroids (adjusted OR, 2.17 [1.01-4.67]). Fracture risk was also increased among children using 30 mg prednisolone or more each day (adjusted OR for fracture, 1.24 [1.00-1.52]) and among those receiving four or more courses of oral corticosteroids (OR, 1.32 [1.03-1.69]). Children who stopped taking oral corticosteroids had a comparable risk of fracture to those in the control group. Our findings suggest that children who require more than four courses of oral corticosteroid as treatment for underlying disease are at increased risk of fracture. It is not entirely clear whether this relates directly to oral corticosteroid use or the underlying disease and its severity. Irrespective of these issues, this group of children is at increased risk of fracture.

Administration, Oral↗
PubMed2002

The menstrual cycle and its effect on the immune status of female endurance runners.

Twenty highly trained, eumenorrhoeic female endurance runners were studied over three consecutive menstrual cycles. Average training distance per week, total years training and mood states were recorded throughout the three cycles. Salivary progesterone and menstrual cycle diaries were recorded over the first two cycles to identify luteal phase onset and the presence of any menstrual irregularities. Saliva samples were collected daily over the third cycle for analysis of immunoglobulin A (IgA) concentration and secretion and saliva flow rate. Two-way analysis of variance (ANOVA) revealed no significant differences in mood states across the phases of the menstrual cycle (P > 0.05). Training logs indicated that training did not alter throughout the 3 month study. One-way ANOVA revealed no significant differences in IgA concentration (P = 0.92), secretion rate (P = 0.84) or saliva flow rate (P = 0.95) across the phases of the menstrual cycle. Pearson's product-moment correlation revealed no relationship between IgA concentration and progesterone between the phases of the cycle (r = 0.39). We conclude that, in ovulatory female endurance runners whose physical and emotional stress are stable, IgA concentration is not significantly affected by fluctuations in progesterone during the menstrual cycle.

Adult↗
PubMed2000

TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes.

Class E vacuolar protein sorting (vps) proteins are required for appropriate sorting of receptors within the yeast endocytic pathway, and most probably function in the biogenesis of multivesicular bodies. We have identified the mammalian orthologue of Vps28p as a 221- amino acid cytosolic protein that interacts with TSG101/mammalian VPS23 to form part of a multiprotein complex. Co-immunoprecipitation and cross-linking experiments demonstrated that hVPS28 and TSG101 interact directly and that binding requires structural information within the conserved C-terminal portion of TSG101. TSG101 and hVPS28 are predominantly cytosolic. However, when endosomal vacuolization was induced by the expression of a dominant-negative mutant of another class E vps protein, human VPS4, a portion of both TSG101 and hVPS28 translocated to the surface of these vacuoles. We conclude that TSG101 and its interacting components are directly involved in endosomal sorting.

Adenosine Triphosphatases↗
PubMed2000

Variability within general practitioner prescribing over time.

AIMS: We have described intra-general practitioner (GP) prescribing variability over time in terms of volume, cost and average item cost of prescription items, within New Zealand general practice. METHODS: Longitudinal data over the financial years 1992-94 were studied for two GP samples. Prescription data for a regional sample of 305 GPs were obtained for the first six months (January to June) from the New Zealand pharmaceutical pricing office, Health Benefits Limited. Prescription data from a second national sample of 74 GPs were obtained from the PreMeC prescription analysis (PAS) database of GPs who had participated in three consecutive September to December prescription analyses. The coefficient of variation was used to measure the intra-GP variability over time in total prescription cost, volume of prescription items and average prescription item cost. RESULTS: The median intra-GP variability over time for the regional GP sample, based on reimbursement data, was 9% in total cost, 9% in total volume and 5% in average item cost. The median intra-GP variability in the national sample was very similar to the regional sample when based on reimbursement data, but when PAS data were used the variability was 16% in total cost, 17% in total volume and 8% average item cost. CONCLUSIONS: The year-on-year, intra-GP variability for cost was 9%, for volume 9-10% and for average item cost 5-6%. Pharmaceutical budget estimates should reflect year-to-year intra-GP prescribing variability of the order of 9%.

Drug Costs↗
PubMed2000

ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking.

The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking that couples membrane association to its ATPase cycle. To investigate the function of mammalian VPS4 in endosomal trafficking, we have transiently expressed wild-type or ATPase-defective human VPS4 (hVPS4) in cultured cells. Wild-type hVPS4 was cytosolic, whereas a substantial fraction of hVPS4 that was unable to either bind or hydrolyze ATP was localized to membranes, including those of specifically induced vacuoles. Vacuoles were exclusively endocytic in origin, and subsets of enlarged vacuoles stained with markers for each stage of the endocytic pathway. Sorting of receptors from the early endosome to the recycling compartment or to the trans-Golgi network was not significantly affected, and no mutant hVPS4 associated with these compartments. However, many hVPS4-induced vacuoles were substantially enriched in cholesterol relative to the endosomal compartments of untransfected cells, indicating that expression of mutant hVPS4 gives rise to a kinetic block in postendosomal cholesterol sorting. The phenotype described here is largely consistent with the defects in vacuolar sorting associated with class E vps mutants in yeast, and a role for mammalian VPS4 is discussed in this context.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2000

Incidence of vertebral fractures in the first three months after orthotopic liver transplantation.

BACKGROUND AND OBJECTIVES: High rates of bone loss and increased fracture incidence have been reported in patients undergoing liver transplantation, mainly within the first post-operative year. The pathogenesis of post-transplantation bone disease has not been clearly established, but the high doses of glucocorticoids used for immunosuppression may contribute. The use of lower doses in recent years has been associated, in some studies, with lower rates of bone loss and decreased fracture incidence. The aim of this prospective study was to establish the incidence of vertebral fractures in the first 3 months in patients undergoing liver transplantation for chronic liver disease and to identify risk factors for fracture in these patients. DESIGN AND METHODS: Thirty-seven adults with end-stage liver disease were studied prospectively prior to and 3 months after liver transplantation. Vertebral fractures were assessed semi-quantitatively from lateral spine X-rays and bone mineral density measured using dual energy X-ray absorptiometry. RESULTS: Prior to transplantation, prevalent vertebral fractures were present in 13 patients (35%). New fractures developed after transplantation in 10 patients (27% of total) and were significantly more common in those with a prevalent vertebral fracture pre-operatively (P<0.02). Osteoporosis, defined as a bone mineral density T score below -2.5, was present in 39% of patients prior to transplantation, but bone mineral density was not helpful in predicting incident fracture, whether measured before or after transplantation. Over the 3-month study period, significant bone loss occurred in the femoral neck (P<0.05) but not the lumbar spine. CONCLUSIONS: Our results demonstrate a high incidence of vertebral fracture in the first 3 months after liver transplantation and indicate that prevalent vertebral fracture is an important risk factor for the subsequent development of fracture in these patients. Prevention of post-transplantation bone disease should focus both on optimizing bone mass prior to transplantation and preventing bone loss in the early post-operative period.

Absorptiometry, Photon↗
PubMed2000

Disassembly of membrane-associated NSF 20S complexes is slow relative to vesicle fusion and is Ca(2+)-independent.

N-ethylmaleimide-sensitive fusion protein (NSF) and its co-factor soluble NSF attachment protein (alpha)-SNAP) are essential components of the synaptic vesicle fusion machinery and form part of a structurally-conserved 20S protein complex. However, their precise function, relative to fusion itself, is not clear. Using a UV-activated cross-linking approach, we have measured the rate at which a single round of NSF-driven ATP hydrolysis leads to 20S complex disassembly within synaptic membranes. Although this rate is substantially faster than previous estimates of NSF-dependent ATP hydrolysis, it remains much lower than published rates for fusion of synaptic vesicles. Furthermore, the stability of 20S complexes is unaffected by Ca(2+) at concentrations that elicit rapid membrane fusion. We conclude that the ATPase activity of NSF does not contribute directly to vesicle fusion, but more likely plays an earlier role in the synaptic vesicle cycle.

Animals↗
PubMed1999

Human rabaptin-5 is selectively cleaved by caspase-3 during apoptosis.

We have previously shown that Xenopus rabaptin-5 is cleaved in apoptotic extracts, with a concomitant reduction in the ability of these extracts to support endosomal membrane fusion (Cosulich, S. C., Horiuchi, H., Zerial, M., Clarke, P. R., and Woodman, P. G. (1997) EMBO J. 16, 6182-6191). In this report we demonstrate that caspase-dependent cleavage is a conserved feature of rabaptin-5. Human rabaptin-5 is cleaved at two sites (HSLD(379) and DESD(438)) in apoptotic HeLa extracts. Cleavage is effected by caspase-3, since it is prevented when caspase-3 activity is either inhibited by Ac-DEVD-CHO or removed by immunodepletion. Moreover, an identical pattern of cleavage is observed using recombinant caspase-3. The action of caspase-3 is highly selective; neither caspase-2 nor caspase-7 are able to cleave recombinant or cytosolic rabaptin-5. Caspase-dependent cleavage of rabaptin-5 generates two physically separated coiled coil-forming domains, the C-terminal of which retains the ability to bind the Rab5 exchange factor rabex-5.

Base Sequence↗
PubMed1998

Interpretation of bone mineral density values in pediatric Crohn's disease.

Patients with Crohn's disease (CD) often have low bone mineral density (BMD) for their chronological age (CA). However, pediatric cases frequently have growth failure and delayed bone age (BA) and height age (HA). Do they really have the amount of osteoporosis as measured by BMD and calculated for their CA? The aim was to compare z-scores for BMD in relation to CA and z-scores corrected for BA or height age in pediatric patients. A group of 43 pediatric patients (mean age, 12 years; 14 girls, 29 boys) with CD in remission, prospectively had BMD (measured by dual energy x-ray absorptiometry) and BA. Abnormally low z-score for BMD (below 2 standard deviation [SD] for CA was found in 19 patients (44%). Among these, 9 patients (21% overall) had a BA of more than 2 SD lower than their CA and 12 had height age at least 2 years below CA. When the BMD z-score in these patients was corrected for their BA and height age, 6 of 9 and 8 of 12 patients had a normal BMD. In conclusion, when corrected for BA or CA delay, BMD was abnormal in 26 to 30% rather than 44% of cases. Correct assessment of BMD in Crohn's disease patients with bone age delay requires interpretation in terms of BA or HA, rather than CA.

Absorptiometry, Photon↗
PubMed1998

Formation and turnover of NSF- and SNAP-containing "fusion" complexes occur on undocked, clathrin-coated vesicle-derived membranes.

Specificity of vesicular transport is determined by pair-wise interaction between receptors (SNAP receptors or SNAREs) associated with a transport vesicle and its target membrane. Two additional factors, N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein (SNAP) are ubiquitous components of vesicular transport pathways. However, the precise role they play is not known. On the basis that NSF and SNAP can be recruited to preformed SNARE complexes, it has been proposed that NSF- and SNAP-containing complexes are formed after SNARE-dependent docking of transport vesicles. This would enable ATPase-dependent complex disassembly to be coupled directly to membrane fusion. Alternatively, binding and release of NSF/SNAP may occur before vesicle docking, and perhaps be involved in the activation of SNAREs. To gain more information about the point at which so-called 20S complexes form during the transport vesicle cycle, we have examined NSF/SNAP/SNARE complex turnover on clathrin-coated vesicle-derived membranes in situ. This has been achieved under conditions in which the extent of membrane docking can be precisely monitored. We demonstrate by UV-dependent cross-linking experiments, coupled to laser light-scattering analysis of membranes, that complexes containing NSF, SNAP, and SNAREs will form and dissociate on the surface of undocked transport vesicles.

Animals↗