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Biomedical subjects

B Vernon-Roberts

Publications and source records attributed to B Vernon-Roberts.

At least 73 records · Page 4Linked to original sources

A rat model of resorption of bone at the cement-bone interface in the presence of polyethylene wear particles.

Resorption of bone and the formation of a membrane at the interface between acrylic cement and bone were induced by particles of high-density polyethylene that were similar in size to those that are present in the tissues surrounding a human joint prosthesis. A non-weight-bearing plug of methylmethacrylate was inserted through the knee joint into the distal part of the femur of the rat. The plug rapidly became surrounded by a shell of bone. After repeated injections of particles of high-density polyethylene into the knee joint, resorption of bone occurred at this stable interface. No resorption of bone occurred after the opposite knee was injected with a control preparation that did not contain particles. The resorption of bone that occurred around the plug after the injection of particles of polyethylene took place in the absence of mechanical causes for loosening and in the absence of infection.

Animals↗

The synovial response to intraarticular cobalt-chrome wear particles.

The intraarticular effects of alloy wear particles similar in size to those present in the tissues around loose total joint prostheses were studied in rat knee joints injected with laboratory-prepared particulate cobalt-chrome. The particles induced rapid proliferation of macrophages and focal degeneration of synovial tissues similar to the response seen in the articular tissues around loose total joint prostheses in humans. Bacteriologic tests excluded infection as a factor. Wear particles may contribute to the changes in the tissues around total joint prostheses and may contribute to bone resorption resulting in prosthetic loosening. Experiments on animals provide useful information about the biocompatibility of materials used in the manufacture of total joint prostheses.

Animals↗

Discitis after discography.

Infection after intradiscal injections has been recognised as a distinct entity, but discitis after discography has often been attributed to an aseptic process or a chemical reaction to the contrast material. We examined the hypothesis that discitis after discography is always due to infection, and report a clinical review and an experimental study. Part I. We reviewed the case records and radiographs of 432 patients who had undergone lumbar discography. When an 18-gauge needle without a stilette had been used, discitis was diagnosed in 2.7% of 222 patients but stiletted needles and a two-needle technique at each level reduced the incidence to 0.7%. Seven patients with discitis after discography had undergone anterior discectomy and fusion; in them the histopathological findings were of a chronic inflammatory response. Bacteria were isolated from the discs of three of the four patients who had open biopsy less than six weeks from the time of discography. These findings suggest that bacteria were initiators rather than promoters of the response. Part II. Multiple level lumbar discography was carried out in mature sheep, injecting contrast material with or without various concentrations of bacteria. Radiographs were taken and the discs and end-plates were examined histologically and cultured for bacteria at intervals after injection. None of the controls showed any evidence of discitis but all sheep injected with bacteria had typical radiological and histopathological changes by six weeks, though cultures were almost all negative. However, at one and two weeks after injection, but usually not after three weeks, bacteria could be isolated. We suggest that all cases of discitis after discography are initiated by infection, and that a very strict aseptic technique should be used for all injections into intervertebral discs.

Adolescent↗

Effect of dietary polyunsaturated fatty acid (PUFA) supplementation on adjuvant induced polyarthritis in rats.

Dietary treatment with fish oil reduced the severity of adjuvant induced polyarthritis in Dark Agouti rats but enhanced disease severity in Wistar-Hooded rats. The difference in effects of fish oil between strains was not related to differences in severity of disease induced in untreated rats. Genetically determined factors may influence the effects of fish oil supplementation on severity of inflammatory diseases.

Animals↗

Osteoarthritis of the hip. Possible protective and causative roles of trabecular microfractures in the head of the femur.

In contrast to the large volume of data on the cartilage and synovial fluid changes, there has been relatively little investigation of the involvement of bone in the genesis of osteoarthritis (OA). Previous researchers have hypothesized that OA follows stiffening of subchondral bone through trabecular microfractures. Although it is widely recognized that marked changes in the subchondral bone are a consistent feature of advanced OA, the nature of the changes in the bone in OA has not received significant attention. The heads of the femur from 67 patients who had joint replacement for advanced OA and 66 autopsy controls without discernible joint disease were examined microscopically to ascertain the number and distribution of trabecular microfractures in coronal slabs and to quantify the mineralization and thickness of trabecular bone in a principal compressive zone. There was a reduction in the number of trabecular microfractures in OA patients, compared with the controls, with a lack of correlation between numbers of microfractures and age in OA patients. There was no evidence for the hypothesis that increased numbers of microfractures led to the increase of bone to support the view that microfractures play a role in maintaining OA joint structure. Structural changes produced relatively sclerotic and porotic groups of OA and two subgroups of the sclerotic group.

Adolescent↗

The generation of reducing ends by exposure of hyaluronic acid to oxygen derived free radicals.

Enzymatic depolymerization of hyaluronic acid (HA) is accompanied by the release of reducing ends irrespective of the linkage cleaved. In this investigation we have examined HA exposed to oxygen-derived free radicals (oxy radicals) in order to determine whether reducing ends are released upon depolymerization. Reducing ends were detected by the assay of Park and Johnson, which is a non-specific but sensitive assay for reducing ends, but only to a minimal degree by the Reissig modification of the Morgan Elson reaction, which will detect N-acetylglucosamine at the reducing end. Exposure of a sample of HA, pre-exposed to streptomyces hyaluronidase, to an oxy radical flux did not result in a decrease in Morgan Elson reactivity thus indicating that post cleavage modification of the reducing end by further reaction with oxy radicals does not account for the lack of Morgan Elson reactivity. In addition reducing ends were also detected by reaction with radiolabelled cyanide to the degree predicted by molecular weight. These findings were interpreted as being consistent with the hypothesis that oxy radical induced depolymerization of HA occurs by preferential cleavage of the glucuronidic linkage thus leaving D-glucuronic acid at the reducing end.

Ferrous Compounds↗

Lymphoid aggregates in the guinea pig large bowel: development of quantitation techniques for number, volume and distribution.

A technique for assessing the number, distribution and volume of the lymphoid aggregates (LA) in the guinea pig large bowel is described. Aggregates could be visualised macroscopically after immersion of the bowel in 10% acetic acid and their number and distribution recorded by tracing on plastic sheets. Serial sections through a sample of 13 LA showed that they were ellipsoidal and this was confirmed by mathematical comparison with hypothetical ellipsoids. In practice, only the length and width of each LA could be measured but, using the sample of 13 LA, it was established that regression analysis enabled the volumes of all except the smallest LA to be predicted accurately from the knowledge of length and width alone.

Acetates↗

The effect of isoxicam-aspirin combinations on the polyurethane sponge implantation model in the rat.

1 Anti-inflammatory effects of isoxicam alone and in combination with aspirin were studied in rats using the polyurethane sponge implantation model of acute inflammation. 2 Dose-response studies were performed to delineate a suppressive (high) and non-suppressive (low) dose of isoxicam prior to studying these doses in combination with aspirin. 3 The results indicate that a combination of aspirin with isoxicam does not have an additive anti-inflammatory effect. 4 The interference demonstrated by aspirin with the anti-inflammatory effects of other NSAIDs such as indomethacin is also demonstrated with aspirin/isoxicam combinations.

Animals↗

Influence of prednisolone and methotrexate on cellular and biochemical aspects of acute and chronic inflammation studied in subcutaneously implanted sponges in rats.

The effects of prednisolone and methotrexate on the histology and the content of collagen and proteoglycans of the inflammatory tissue in polyurethane sponges impregnated with heat killed M. tuberculosis and implanted subcutaneously in hooded Wistar rats for up to 63 days were studied. Drugs were administered during the 6-day period before sponge removal 7, 21, 35, 49 and 63 days after implantation. Our findings indicate that prednisolone and methotrexate have profound effects on the cellular events of acute and chronic inflammation, and influence the synthesis or degradation of connective tissue macromolecules at certain stages of the inflammatory process.

Acute Disease↗

Discitis following chemonucleolysis. An experimental study.

Although infection following intradiscal injections has been recognized as a distinct entity, discitis following chemonucleolysis has been often attributed to a chemical reaction from chymopapain. In the first part of this study the effect of chymopapain and Conray 280 on a wide range of bacteria was measured in vitro. Chymopapain was found to have a bactericidal effect on all bacteria tested, which was more pronounced with gram positive organisms, whereas Conray 280 showed very little if any antibacterial effect after 48 hours. The aim of the second part of the study was to test the hypothesis that discitis following intradiscal chymopapain injection is due to infection and not to a chemical reaction. Multiple level lumbar intradiscal injections were carried out in eight mature sheep. Sixteen discs in four sheep were injected with a mixture of reconstituted chymopapain and a Staphylococcus epidermidis suspension. Sixteen discs in another four sheep were injected with reconstituted chymopapain only. All sheep were sacrificed at 6 weeks and the discs and end-plates were examined radiologically, and by histopathology and nuclear material was cultured for bacteria. None of the controls showed any evidence of discitis, whereas all sheep injected with bacteria had typical radiologic and histopathologic changes of discitis. However, in most cases in which end-plate lesions were well established there was no evidence of bacteria at sacrifice. These findings support the opinion that discitis following intradiscal injection is always due to infection introduced by the needle tip.

Animals↗

Biodistribution of 64Cu in inflamed rats following administration of two anti-inflammatory copper complexes.

64Cu was administered in two anti-inflammatory formulations to normal rats and to rats with 2 forms of local inflammation, namely (a) an acute paw oedema (elicited with carrageenan) or (b) a chronic granulomatous response to an implanted irritant (Mycobacterium tuberculosis in a polyurethane sponge). The copper formulations used were (i) a slow release one consisting of Cu(II) salicylate applied dermally with ethanol/DMSO and (ii) short acting hydrophilic complex (Cu(I)Cu(II)-penicillamine)5- given subcutaneously. Three types of changes in copper biodistribution with these forms of inflammation were discerned based on determination of 64Cu and copper content in the following organs: inflammatory locus (foot or sponge implant), kidney, liver, spleen, adrenals, brain, blood, thymus, heart, and skin (site of application). The most evident changes were in the kidneys, liver, spleen, adrenals, thymus and serum from animals with chronic granulomatous inflammation. In contrast, a short term acute inflammatory stress (carrageenan paw oedema) had little effect. While copper D-penicillamine (applied subcutaneously) appeared to move as a bolus through the animals, the results with the percutaneous copper salicylate formulation are consistent with it providing a slow release source of copper(II). Exogenous 64Cu from both formulations was sequestered at inflammatory sites (relative to serum). This may partly explain how applied copper complexes can be anti-inflammatory.

Administration, Topical↗

In vitro antioxidant properties of potential biotransformation products of salicylate, sulphasalazine and amidopyrine.

2,3-and 2,5-dihydroxybenzoate (formed from salicylate by nonenzymatic or enzymatic hydroxylation), and 5-aminosalicylate (a prime metabolite of sulphasalazine) are highly efficient quenchers of the chemiluminescence (CL) produced by an oxy radical flux. Monohydric phenols (including salicylate) and meta-dihydric phenols are virtually inactive. These findings suggest that the para- or ortho-configuration of hydroxy/amino groups is important for this activity. These differences in activity between 2,3- and 2,5-dihydroxybenzoate, 5-aminosalicylate and monohydric phenols/2,4-, 2,6-dihydroxybenzoate were not seen in assays monitoring hydroxyl radicals. 4-aminophenazone (an oxidation product of both amidopyrine/aminopyrine and isopyrine), 4-hydroxyphenazone and some dietary catechols (and ascorbate), are also quenchers of oxy radical-associated CL.

Aminopyrine↗

Histomorphometric changes in the trabecular structure of a selected stress region in the femur in patients with osteoarthritis and fracture of the femoral neck.

Histomorphometric changes in the trabecular structure of the principal compressive stress region in the femur in patients with osteoarthritis and fracture of the femoral neck are described. Femoral heads were obtained from patients who had surgery for the treatment of femoral neck fracture or total hip replacement for advanced osteoarthritis. Blocks from the principal compressive region of a coronal slice were sampled systematically to prepare 10 microns sections for automated analysis. There was no significant difference in the mineral bone content of the osteoarthritic (OA) and fractured neck of femur (FNOF) cases or between males and females for each group. The regression of mineralized bone on age was significant for OA data, showing a decrease in mineralized bone volume with age, whereas there was no significant relationship for the FNOF data. Surface density was significantly lower in the OA group than in the FNOF group despite the fact there is no difference in the mineralized bone. The regression of surface density on age was not statistically significant in both groups, although regression of surface density on the mineralized bone was significant for both groups and demonstrated that OA cases generated less surface than FNOF cases for the same amount of mineralized bone volume. The trabeculae in OA were significantly thicker than in FNOF, and spacing in OA was significantly greater than in FNOF. The regression of trabecular thickness and spacing on age was not significant for either OA or FNOF. For OA, thickness and spacing showed a significant regression on the mineralized bone volume, positive and negative, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A study of calcergy in the rat induced by the implantation of polyurethane sponges soaked in lead acetate.

Polyurethane sponges were soaked in a 5 mg/ml solution of lead acetate, dried, and implanted subcutaneously in rats. Sponges soaked in distilled water were implanted as controls. The reaction to the sponges was studied from 5 h to 140 days after implantation, utilising sponge dry weight gain, rate of ingrowth of granulation tissue, histology and electron microscopy. Five hours after implantation, test sponges showed lead phosphate deposits in the central sponge zone and by one day the deposits stained positively for calcium. Transmission electron microscopy (TEM) showed needle-shaped crystals of hydroxyapatite. Ingrowth of granulation tissue into test sponges was delayed. Breakdown of the sponge matrix was observed in control sponges after 140 days. This model highlighted the physicochemical nature of the calcergic reaction, implicating fluid transudates/exudates in the initial stages.

Animals↗

Carrageenan colitis in the guinea pig: pathological changes and the importance of ascorbic acid deficiency in disease induction.

In guinea pigs deprived of ascorbic acid, the oral administration of degraded E. spinosum carrageenan induced mild to moderate colitis, while E. cottonii consistently induced severe colitis. A variable degree of colitis was observed in scorbutic animals not receiving carrageenan. By contrast, in animals given large daily supplements of ascorbic acid, neither type of carrageenan consistently induced colitis and severe disease was rarely observed. The severe colitis induced by E. cottonii in scorbutic animals markedly affected the mid and distal colon and showed histological changes similar to human ulcerative colitis.

Animals↗

A morphological study of macrophage and synovial cell interactions with hydroxyapatite crystals.

Hydroxyapatite crystals have been found in synovial fluids and periarticular spaces in association with osteoarthritis. This study examined the morphology of the interaction of macrophages and synovial cells with hydroxyapatite in order to determine the fate of hydroxyapatite over an extended culture period. Mouse peritoneal macrophages and bovine synovial cells were grown as monolayers. The morphology of the interaction between hydroxyapatite crystals (HAC) and these cells was studied by light microscopy, transmission and scanning electron microscopy for up to 14 days. Phagocytosis of HAC, phagosome formation, and concentration of crystal aggregates around the cells began within four minutes of their addition to the cultures. Phagocytosis and cellular aggregation continued after this time. HAC caused minimal cellular disruption despite the uptake of large amounts of crystalline material and significant cellular enlargement. HAC remained within cells for the duration of the study without any apparent dissolution by the cells. Whether macrophages are stimulated to produce interleukin I as a result of HAC uptake is currently under investigation.

Animals↗

Ambivalent properties of gold drugs in adjuvant induced polyarthritis in rats.

We evaluated the antiarthritic activity of gold sodium aurothiomalate (GSTM) and auranofin (AF) against experimental polyarthritis induced in 3 rat strains using 3 different adjuvants. These 2 gold drugs were found to either stimulate, inhibit or have no effect upon the development of arthritis, dependent upon the rat strain and/or the adjuvant used. The ambivalent antiarthritic activities of GSTM and AF did not appear to be associated with any variations in serum gold levels. These results highlight the need for caution in studying gold drugs using the adjuvant polyarthritic model in the rat and, if used, the need to define clearly the strain/adjuvant/gold drug combination. Within these constraints however, our findings support the concept that GSTM and AF have different mechanisms of action.

Animals↗