Search PubMed⌕ Search

Biomedical subjects

R A Brooks

Publications and source records attributed to R A Brooks.

At least 37 records · Page 2Linked to original sources
PubMed2002

Testing bone substitutes in a small animal model of revision arthroplasty.

This study evaluated a modification of the rat-pin model to enable testing of bone substitute materials. The model was characterized using the ceramic, beta-tricalcium phosphate (betaTCP) as a filler. A 1 mm wide, 3.6 mm deep defect was created around a stainless steel (SS) implant in the proximal tibia of a rat. This defect was filled with a ceramic powder. Large particles (90-312microm) of betaTCP were mixed with Gelfoam to form a paste which was then molded around the proximal end of either an uncoated SS pin or a pin coated with hydroxyapatite (HA). The pin with its ceramic collar was then implanted into the proximal tibia of 16 male Sprague Dawley rats. Two animals with coated implants and two with uncoated implants were sacrificed at 3, 6, 14 and 26 weeks. Longitudinal sections of each tibia were stained with toluidine blue and labeled for tartrate resistant acid phosphatase (TRAP). There was initial fibrous tissue interposition around the implants which was completely remodeled around the HA coated pins but which persisted in apposition to the SS pins. The remodeling process peaked at 3 weeks around the HA coated pins and at 6 weeks around the uncoated implants. There was little remodeling around either implant by 26 weeks. There was considerable residual betaTCP present which was well tolerated as the particles were often encased in bone. The model has several characteristics of revision arthroplasty and the results demonstrate the suitability of this model for testing bone substitutes.

Journal Article↗
PubMed2002

Endotoxin contamination of particles produces misleading inflammatory cytokine responses from macrophages in vitro.

Particulate prosthetic materials are often studied by adding them to monocytic cells in vitro and measuring the release of cytokines as an indicator of their inflammatory potential. Endotoxin is known to be a contaminant of particle preparations and also stimulates the release of cytokines. It is usual to use a proprietary endotoxin test to avoid erroneous results. Four different formulations of cement were found to be free from endotoxin using standard, gel-clot tests but stimulated different levels of release of cytokines from macrophages. These differences were explained when a more sensitive, kinetic endotoxin assay showed that release correlated with minor contamination with endotoxin. In a repeat experiment using cement particles with low or undetectable levels of endotoxin by kinetic assay, differences in the ability of the formulations to stimulate the release of cytokines were not seen. Endotoxin is adsorbed on to the surface of particles and it is this combination which stimulates increased release of cytokines. In both the above methods for determination of endotoxin, the water in which the particles had been soaked was examined rather than the particles directly. Further investigations showed that a kinetic assay directly on a particle suspension is the most sensitive method to measure contamination with endotoxin.

Adsorption↗
PubMed2002

Circulating levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in patients with severe head injury.

There is evidence to suggest that fractures heal more rapidly in patients with a head injury as a result of systemic factors released from the site of this injury. We have measured the circulating level of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in serum because of their known involvement in the stimulation of the activity of osteoblasts and the healing of fractures. The serum level of IGF-1 was significantly lower in patients with both head injury and fracture and fracture only compared with that in healthy volunteers (p < 0.01 and p < 0.02, respectively). The level of IGFBP-3 was also significantly lower in patients with both head injury and fracture (p < 0.01). Our findings showed, however, that the level of IGF-1 and IGFBP-3 varied from week to week in both the patients and healthy control subjects. These results indicate that the levels of circulating IGF-1 and IGFBP-3 are unlikely to be responsible for the altered healing of fractures seen in conjunction with head injury.

Adolescent↗
PubMed2001

On T2-shortening by weakly magnetized particles: the chemical exchange model.

Chemical exchange (CE) theory is compared with two theories of T2-shortening caused by microscopic magnetic centers: inner- and outer-sphere relaxation theory (long-echo limit) and mean gradient diffusion theory (short-echo limit). The CE equation is shown to be identical to these theories in the respective limits and appropriate parameter relationships are derived for spherical particles. The theories are then compared with computer simulations of spherical particles and with a recent general theory, with good agreement in the asymptotic regions. The CE model also reproduces the essential relaxation characteristics in the intermediate range. Finally, good agreement of a CE model with simulations for magnetized cylinders is also demonstrated. The discussion is limited to weakly magnetized particles such that the maximum phase shift during an echo interval is less than one radian, permitting the use of the Luz-Meiboom CE equation. Published 2001 Wiley-Liss, Inc.

Computer Simulation↗
PubMed2001

Correlation of synovial fluid cytokine levels with histological and clinical parameters of primary and revision total hip and total knee replacements.

We retrieved synovial tissue and fluid samples from patients undergoing primary total hip replacement (THR) (n 15), revision of aseptically loose THR (n 12), primary total knee replacement (TKR) (n 13) and revision of aseptically loose TKR (n 6). Several histological parameters were assessed on a relative scale of 14. Primary TJRs were clinically evaluated for degree of osteoarthrosis. Revision TJRs were assessed for migration of the implant, gross loosening and the degree of radiolucency. Cytokine levels in synovial fluid were determined with ELISA. All cytokines were significantly higher in revision TJRs than in primary replacements, as were the degree of macrophage and giant cell infiltration. We found no relationship between any clinical variable and the levels of any cytokine, but migration of the implant was related to the presence of PE debris. A significant correlation was seen between the presence of macrophages and the levels of IL-1beta, IL-8 and IL-10, but not IL-6. No differences were noted between hips and knees for any of the variables, except in the levels of IL-6, where higher levels were found in THRs. These results suggest a unique role for IL-6 that requires further investigation.

Adult↗
PubMed2001

Evaluation of the Oxford protocol for total spinal clearance in the unconscious trauma patient.

BACKGROUND: Prolonged use of spinal precautions in unconscious trauma patients is associated with significant morbidity. The trauma service of the John Radcliffe Hospital uses full-length radiography, computed tomographic scanning, and dynamic screening of the cervical spine to clear the spine at the earliest opportunity. METHODS: The results in 210 consecutive patients were reviewed. Seventy-eight patients underwent dynamic screening of the cervical spine. RESULTS: Five of these patients had a cervical fracture or instability. One patient had demonstrated minor changes only on plain radiography but gross instability on dynamic screening. There were no neurologic sequelae from dynamic screening and no fractures were missed. Collar removal was possible in all but one patient a median 3 days before extubation and 1 day after admission to the intensive care unit. CONCLUSION: Full length spinal radiography and dynamic cervical screening may allow early and safe discontinuation of spinal precautions in the unconscious trauma patient in whom clinical signs are absent or unreliable.

Adolescent↗
PubMed2001

Bacterial recolonization during foot surgery: a prospective randomized study of toe preparation techniques.

Fifty patients undergoing foot or ankle surgery were randomized into two groups for the purposes of toe preparation. Twenty-four patients underwent a standard preparation which included placing antiseptic between the toes while 26 were additionally cleaned by sliding a gauze swab soaked in topical antiseptic back and forth several times. Povidone iodine followed by chlorhexidine in alcohol was used in both groups. All toes were covered by a sterile glove during surgery unless the toes themselves were to be operated upon. Bacteria were cultured from the toe clefts in 4% of all patients immediately following preoperative disinfection. Significantly fewer patients whose toes had been additionally scrubbed (group 1) showed bacterial recolonization at the end of surgery compared with those undergoing a standard prep (group 2) (7.7% vs 20.8%). We conclude that additional scrubbing of toe clefts prior to surgery reduces the incidence of recolonization of bacteria during the surgical procedure.

Anti-Infective Agents, Local↗
PubMed2001

Inflammatory responses of human primary macrophages to particulate bone cements in vitro.

We have investigated whether the particle-stimulated release of inflammatory cytokines from human primary macrophages in vitro was dependent upon the type of bone cement used. Particles of clinically relevant size were produced from Palacos R without radio-opacifier, Palacos R with BaSO4, Palacos R with ZrO2 and from CMW3 which contains BaSO4. All four preparations produced significantly greater release of tumour necrosis factor alpha, interleukin-6 and interleukin-1 beta than a negative control but there were no significant differences between them. The differences in the ability to stimulate bone resorption and in clinical performance between proprietary bone cements previously recorded are not explained by the release of the cytokines most commonly implicated in osteolysis.

Acrylic Resins↗
PubMed2001

The effects of particulate bone cements at the bone-implant interface.

We used a rat model in vivo to study the effects of particulate bone cements at the bone-implant interface. A ceramic pin was implanted into the tibiae of 48 rats. Three types of particle of clinically relevant size were produced from one bone-cement base without radio-opacifier, with zirconium dioxide (ZrO2) and with barium sulphate (BaSO4). The rats were randomly assigned to four groups to receive one of the three bone cements or normal saline with 2% v/v Sprague-Dawley serum as the control. A total of 10(9) particles was injected into the knee at 8, 10 and 12 weeks after the original surgery. The animals were killed at 14 weeks and the tibiae processed for histomorphometry. The area of fibrous tissue and the gap between the implant and bone were measured using image analysis. All three types of particle were associated with a larger area of bone resorption than the control. Only in the case of the BaSO4-containing cement did this reach statistical significance (p = 0.01). Particles of bone cement appear to promote osteolysis at the bone-implant interface and this effect is most marked when BaSO4 is used as the radiopaque agent.

Animals↗
PubMed2000

Dynamic relaxometry: application to iron uptake by ferritin.

We introduce dynamic relaxometry as a novel technique for studying biochemical reactions, such as those leading to mineral formation (biomineralization). This technique was applied to follow the time course of iron oxidation and hydrolysis by the protein ferritin. Horse spleen apoferritin was loaded with single additions of 4, 10, 20, 40, and 100 ferrous ions per protein, and with multiple additions of 4, 10, 20, and 100 ferrous ions. The NMR T2 relaxation time was then measured sequentially and continuously for up to 24 h. At low loading factors of 4-10 Fe atoms/molecule, the iron is rapidly bound and oxidized by the protein on a time scale of approximately 15 s to several minutes. At intermediate loading factors (10-40), rapid initial oxidation was observed, followed by the formation of antiferromagnetic clusters. This process occurred at a much slower rate and continued for up to several hours, but was inhibited at lower pH values. At higher loading factors (40-1000), iron oxidation may occur directly on the core, and this process may continue for up to 24 h following the initial loading. Dynamic relaxometry appears to be a potentially powerful technique that may well have applications beyond the study of iron uptake by the ferritin protein.

Animals↗
PubMed2000

Diagnosis and imaging studies of traumatic hip dislocations in the adult.

Traumatic dislocation of the hip represents a major injury that is associated with significant morbidity. In particular, the risk of osteonecrosis of the femoral head is greatly affected by the time it takes to reduce the hip. Therefore, thorough understanding of the clinical and radiologic features is essential if this injury is to be recognized and treated promptly. Most patients present in severe distress after a high-energy injury such as a motor vehicle accident. Associated injuries, particularly of the knee, are common and the leg usually is held in a specific posture characteristic of the direction of dislocation. Plain anteroposterior radiographs of the pelvis will clearly show the dislocation in most patients but lateral views or a computed tomography scan may be required to confirm the diagnosis and to show the direction if the signs are subtle. Associated acetabular wall fractures and femoral head fractures also may be identified by computed tomography scans. After reduction, plain radiographs alone are not adequate to assess reduction; computed tomography is more sensitive in detecting osteochondral fragments and may reliably detect residual subluxation of 2 mm in any part of the joint. Magnetic resonance imaging is useful in detecting changes of osteonecrosis but rarely is indicated in the early treatment of this condition.

Adult↗
PubMed2000

The effects of the concentration of high-density polyethylene particles on the bone-implant interface.

We used a rat model in vivo to study the effects of the concentration of polyethylene particles on the bone-implant interface around stable implants in the proximal tibia. Intra-articular injections of 10(4), 10(6) or 10(8) high-density polyethylene (HDPE) particles per joint were given 8, 10 and 12 weeks after surgery. The animals were killed after 14 and 26 weeks and the response at the interface determined. Fibrous tissue was seen at the bone-implant interface when the head of the implant was flush with the top of the tibia but not when it was sunk below the tibial plateau. In the latter case the implant was completely surrounded by a shell of bone. The area of fibrous tissue and that of the gap between the implant and bone was related to the concentration of particles in the 14-week group (p < 0.05). Foreign-body granulomas containing HDPE particles were seen at the bone-implant interface in animals given 10(8) particles. The pathology resembles that seen around prostheses with aseptic loosening and we suggest that this is a useful model by which to study this process.

Animals↗
PubMed1999

Protease inhibitor use among a community sample of people with HIV disease.

OBJECTIVES: Protease inhibitors have become integral to HIV disease management. This paper examines sociodemographic factors affecting patient use and perceived knowledge of protease inhibitors, and the relationship between protease inhibitor use and perceived health. METHODS: 1034 people with HIV disease from a large AIDS services organization completed a mailed self-administered survey that assessed sociodemographics, protease inhibitor use and perceived knowledge, and perceived change in health status over the previous year. Multiple logistic regression was used to determine sociodemographic factors independently associated with protease inhibitor use and perceived knowledge, and perceived overall health status. RESULTS: Two thirds (66%) of correspondents included in the sample were currently taking protease inhibitors and 52% reported being very knowledgeable about these medications. Adjusting for sociodemographic factors, those who were currently not taking protease inhibitors were more likely to be African American, non-English speaking, earning <$9600 U.S. annually, or uninsured. Among protease inhibitor users, those who reported less knowledge about the drugs were more likely to be nonwhite, earning <$9600 U.S. annually, and not college educated. Protease inhibitor use was independently associated with perceived improved overall health and having been college educated. CONCLUSIONS: Further efforts should be directed toward increasing use and knowledge of protease inhibitors among disadvantaged populations.

Adult↗
PubMed1999

Relaxometry and magnetometry of the MR contrast agent MION-46L.

MION-46L is an ultrasmall monocrystalline superparamagnetic (SPM) iron oxide that is of current interest as an MR contrast agent. It is believed to consist primarily of small maghemite or magnetite crystals that possess a SPM moment, but the exact magnetic properties and related mechanisms of T(1) and T(2) proton relaxation enhancement are not well understood. We have obtained a comprehensive data set consisting of magnetization curves, EPR spectra, and 1/T(1) and 1/T(2) nuclear magnetic relaxation dispersion (NMRD) profiles for this contrast agent. The magnetization curves show a primary curvature consistent with a SPM moment of 10,300 Bohr magnetons (BM) per particle. In addition, there is a secondary high-field curvature that is consistent with a smaller SPM moment of 1600 BM, which may be responsible for the observed high-field increase in 1/T(2). Finally, there appear to be a considerable number of paramagnetic ions present that are needed to account for the high-field increase in magnetization, and that can provide an alternative explanation for the magnitude of the low-field T(1) plateau. This "three-phase model" appears to be successful in explaining in a self-consistent and quantitative manner the combined results of the magnetometry, relaxometry, and EPR studies. Magn Reson Med 42:379-384, 1999. Published 1999 Wiley-Liss, Inc.

Contrast Media↗
PubMed1999

Corrected equations for susceptibility-induced T2-shortening.

Local field gradients created by paramagnetic entities shorten water proton relaxation times, particularly T2. This "novel" relaxation mechanism, now known as susceptibility-induced relaxation, was described twenty years ago by Gueron, and later extended by others to superparamagnetic particles which have a much larger magnetization. Unfortunately, because of subtle but significant errors, those results are valid only in the strict zero-field limit. These errors are corrected in the present article, and new versions of the relaxation equations are presented. The correction is shown to be significant, not only for transverse and longitudinal relaxation in aqueous superparamagnetic colloids, where the "Gueron" effect is known to be important, but even in some cases for transverse paramagnetic relaxation.

Colloids↗
PubMed1999

The mutagenicity of benzo[a]pyrene in mouse small intestine.

We have investigated the mutagenicity of benzo[a]pyrene (B[a]P) in small intestine using the Dlb-1 locus assay in the mouse. Administration of B[a]P by the oral and i.p. routes had markedly different effects on the number of Dlb-I mutations and the pattern of induction of cytochrome P-4501A1 (CYP1A1). In Ahr-responsive animals i.p. injection resulted in marked induction in crypt cells along the length of the small intestine, with some induction in the villus cells. In contrast, after oral administration, CYP1A1 induction was evident only in the villus cells, and this declined distally. The intensity and speed of induction in Ahr-responsive animals was such that the genotoxic effect of a single injection of B[a]P could not be augmented by prior treatment with non-genotoxic inducers such as beta-napthoflavone and TCDD. Oral B[a]P treatment resulted in a decrease in the number of mutations when compared with the i.p. route. Studies in congenic Ahr-non-responsive versus Ahr-responsive mice indicated that induction of CYP1A1 was associated with increased numbers of Dlb-1 mutations. Mutation induction in Ahr-non-responsive mice in the absence of detectable CYP1A1 in either liver or small intestine indicates that an appreciable portion of B[a]P activation to a genotoxin must be by other than a CYP1A1 mediated route. These data show that B[a]P is a potent small intestinal mutagen at the Dlb-1 locus.

Animals↗
PubMed1999

NMSP binding to dopamine and serotonin receptors in MPTP-induced parkinsonism: relation to dopa therapy.

We tested the hypothesis that N-methylspiperone binding to dopamine D2 receptors must be reduced when L-dopa therapy of parkinsonism augments the binding of dopamine to the receptors and improves the clinical state expressed by the Hoehn & Yahr stage. A patient with MPTP-induced parkinsonism underwent two positron emission tomographic studies of the D2-like dopamine receptors with N-[11C]methylspiperone (NMSP). The first study took place 3 days after cessation of the L-dopa medication, the second 5 days after its resumption. Noticeable clinical deterioration occurred during both studies, consistent with significant dopamine receptor blockade by NMSP and elevated NMSP binding in both scans. The dopa treatment did not reduce the NMSP binding. On the contrary, the rate of binding of NMSP (k3) was increased on-dopa, compared to off-dopa. The increase was consistent with the slightly greater dopamine receptor density estimated after resumption of the dopa therapy. The NMSP binding to serotonin receptors suggested lower synaptic serotonin on-dopa than off-dopa. The results are consistent with negative correlation between the Hoehn & Yahr stage and the amount of dopamine bound to dopamine D2 receptors. Low synaptic serotonin may explain the depression seen in some patients on dopa for Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗