Biomedical subjects

B Vernon-Roberts

Publications and source records attributed to B Vernon-Roberts.

At least 19 recordsLinked to original sources

PubMed1992

A longitudinal study of the matrix changes induced in the intervertebral disc by surgical damage to the annulus fibrosus.

A 5 x 5-mm anterolateral incision was made in the annulus fibrosus (AF) of lumbar discs of 16 sheep; four animals of similar age not operated on were used as controls. The experimental animals were sacrificed 2, 4, 6, 8, 12, and 18 months postoperatively (PO), and the incised and adjacent lumbar discs were collected. Discs were dissected into four zones: AF (zones 1 and 2) and nucleus pulposus (NP) (zones 3 and 4) corresponding to the half of the AF in which the cut was made and its opposite half, and the complementary halves of the NP. Each zone was analyzed for moisture, proteoglycan (PG), collagen, and noncollagenous protein (NCP) content. The PG extractability, aggregation, and hydrodynamic size were also examined. The NP of injured discs showed a significant loss of PGs and collagen 8 months PO, but NCP levels increased. In the incised discs, PG aggregation initially declined but recovered to within control values 6-8 months PO. The NP of discs adjacent to the incised disc also showed time-dependent changes in matrix components that included loss of collagen and PG; however, the AF matrix remained essentially uneffected. Double immunodiffusion studies indicated that a sizeable proportion of the NCPs present in the injured discs (but not the adjacent lumbar discs) were derived from serum.

Animals↗

PubMed1992

Comparative study of iliac crest and subchondral femoral bone in osteoarthritic patients.

This is a study of trabecular bone changes in selected regions of the femoral head. Iliac crest bone from osteoarthritic (OA) and control groups is compared to the bone from regions in the femoral head. The regions are the subchondral principal compressive and tensile areas. These areas of highest and lowest stress undergo dramatic change with OA. The compressive region has total cartilage loss and eburnation. Bone histomorphometry was done on undecalcified tissue sections stained by the von Kossa silver method and counter-stained with haematoxylin and eosin. Iliac crest histomorphometry is similar for the OA and control groups. The femoral trabecular structure in the stress regions changes in opposing directions with OA. In the compressive region the structural variables (BV/TV and BS/TV) increase [corrected], and in the tensile region decrease. Femoral bone turnover indices (OV/TV, OS/BS, and ES/BS) are no different, but femoral bone structure is different from that of the iliac crest. In OA patients there is no significant increase in iliac crest trabecular bone volume. The iliac crest is not useful to assess the bony changes in femoral OA.

Aged↗

PubMed1992

A cadaveric study comparing discography, magnetic resonance imaging, histology, and mechanical behavior of the human lumbar disc.

The aims of this study were 1) to compare discography and magnetic resonance imaging scanning on cadaver specimens and to correlate these imaging procedures by examining all the discs histologically; and 2) to study the extent to which the amplitude of rotational movement in the neutral and flexed position at a certain level correlates with the morphologic appearance of that disc. Twenty-four human lumbar spines were harvested from cadavers between the ages of 19 and 75 years. Each specimen underwent standard radiography, magnetic resonance imaging scanning, discography, histologic examination, and measurement of axial rotation in a torsion apparatus. For practical reasons, all specimens did not undergo all of the examinations. Not all peripheral anular lesions were detected by discography. Histology showed rim lesions of the anterior anulus in 18% of discs with normal discography. The overall incidence of anterior and posterior anular tears was greater in discs where larger amplitudes of rotation were observed. To which extent the one is a consequence of the other or vice versa is not clear. Magnetic resonance imaging was found to be less specific than discography. However, it must be emphasized that no axial magnetic resonance imaging scans were taken in this study. Discs with significantly decreased amounts of nuclear material (observed at histology) can still produce normal magnetic resonance imaging images. Infolding of the inner layers of the anulus fibrosus (33% anterior, 4% posterior) was a frequently observed feature.

Adult↗

PubMed1992

Changes in endplate vascularity after an outer anulus tear in the sheep.

In 31 2-year-old sheep, a 5-mm deep cut was made parallel to the end plates in the left anterolateral anulus fibrosus of 3 randomly selected lumbar intervertebral discs. At 2 months, the area of the end plate occupied by blood vessels on the left (operated) side had increased significantly (P less than 0.05) in the cranial end plate to 9.94%, and to 9.39% in the caudal end plate, compared with nonoperated values of 5.17% (cranial) and 5.87% (caudal). One year after operation, these elevated values had diminished significantly (P less than 0.05) to 7.92% (cranial) and 7.13% (caudal), and continued to decline progressively to 7.48% (cranial) and 6.88% (caudal) by 2 years. In contrast, no significant differences were found on the right (nonoperated) side of the discs. Thus, there was an early proliferation of vascular channels in the end plate in the vicinity of the experimental anular lesion, but not on the nonoperated side of the same disc. Thereafter, the end plate vascularity progressively diminished toward a normal level.

Animals↗

PubMed1992

Trabecular spacing in post-menopausal Australian women with and without vertebral fractures.

Histomorphometric measurements were made from iliac crest biopsies of 32 women with vertebral fractures and 37 women without fracture. All were post-menopausal Australian women who had presented with back pain to a hospital out-patient endocrinology clinic. Bone from the fracture cases was characterised by loss of individual trabecular elements, with the remaining trabeculae being spaced further apart than those in the non-fracture women (p less than 0.0001). This resulted in a significant decrease in trabecular bone volume (p less than 0.01). In addition osteoid surface was reduced (p less than 0.01). Dynamic parameters of bone turnover were not significantly different between the two groups. These data should be useful for the assessment of iliac bone histomorphometry in Australian post-menopausal women suspected of having osteoporosis.

Aged↗

PubMed1992

Annular tears and disc degeneration in the lumbar spine. A post-mortem study of 135 discs.

We studied 135 lumbar discs from 27 spines removed post-mortem from subjects of an average age of 31.5 years. Defects of the annulus fibrosus were classified as peripheral, circumferential or radiating; the nucleus pulposus as normal, moderately or severely degenerate. Peripheral tears were more frequent in the anterior annulus, except in the L5-S1 disc. Circumferential tears were equally distributed between the anterior and the posterior annulus. Almost all the radiating tears were in the posterior annulus, and closely related to the presence of severe nuclear degeneration. Histology suggested that peripheral tears were due to trauma rather than biochemical degradation, and that they developed independently of nuclear degeneration. The association of peripheral annular lesions with low back pain is uncertain but our study suggests that they may have a role in the pathogenesis of discogenic pain.

Adolescent↗

PubMed1992

The prostaglandin E1 analogue, misoprostol, regulates inflammatory cytokines and immune functions in vitro like the natural prostaglandins E1, E2 and E3.

We examined whether some immune functions related to the action and production of cytokines could be regulated by the natural prostaglandins E (PGE) and the PGE1 (ester) analogue, Misoprostol. PGE1,2,3 and Misoprostol inhibited: (1) the mitogenic activity of interleukin-1 (IL-1) for mouse thymocytes; (2) spreading of mouse macrophages on glass; (3) tumour necrosis factor (TNF) (alpha and beta) production by human peripheral blood mononuclear cells and rat macrophages; (4) IL-1 production by rat and mouse peritoneal macrophages; and (5) interferon-gamma (IFN-gamma) production by human peripheral blood mononuclear cells. These PGE had little effect on IL-1 production by human monocytes. By contrast, they all enhanced IL-6 production by rat and mouse macrophages and human monocytes. These effects were noted at concentrations below 500 nM (even as low as 10 nM). The relative potency of the prostanoids tested for both inhibitory and stimulatory effects was PGE1 = PGE2 = or greater than PGE3 greater than Misoprostol greater than PGA2 much greater than PGF1-alpha = PGF2-alpha = PGD2 (no effect). There is strong evidence that PGE1,2,3 and Misoprostol bind to the same receptor(s) and trigger the second messenger, cAMP, since dibutyryl cAMP (a lipophilic analogue of cAMP) had the same effects as the PGE. These PGE also induced elevated intracellular cAMP levels in and competed with [3H]PGE2 for binding to human and rat cells with the same relative potencies as described above.

Animals↗

PubMed1991

The effects of some anti-arthritic drugs and cytokines on the shape and function of rodent macrophages.

Non-steroidal antiinflammatory drugs (NSAID) enhanced the spreading of mouse and rat peritoneal macrophages attached to either plastic or glass. This was probably due to drug inhibition of prostaglandin E2 (PGE2) production since spreading was also inhibited by adding exogenous PGE2. Corticosteroids (dexamethasone, cortisol and prednisolone) and some immunosuppressants (6-mercaptopurine, methotrexate, but not cyclosporin-A) also enhanced in-vitro spreading of murine peritoneal macrophages. Some recombinant cytokines (human tumour necrosis factor alpha and beta, murine tumour necrosis factor alpha, and murine interferon gamma, but not human interferon gamma) also enhanced the spreading of mouse peritoneal macrophages in vitro. Scanning electron microscopy revealed significant differences in morphology of cells induced to spread by these drugs and cytokines. NSAID treatment also enhanced macrophage clumping in vitro, indicating that cell spreading may play an important role in the resolution of inflammatory processes and/or the formation of multinucleated giant cells.

Adrenal Cortex Hormones↗

PubMed1990

Zinc monoglycerolate: a slow-release source of zinc with anti-arthritic activity in rats.

Zinc repletion by parental administration of zinc monoglycerolate (ZMG) or certain other lipophilic zinc complexes, suppressed the development of adjuvant-induced polyarthritis in rats. While ZMG was effective when given parenterally over various limited time schedules (immunosuppressant, therapeutic, singledose), it was not effective given orally. The complex showed no acute anti-inflammatory activity in the carrageenan paw oedema assay and little gastric-intestinal or other organ toxicity. When injected s.c. it caused very much less local irritation than most zinc salts. Being lubrous, ZMG could be applied as the dry powder for rubbing into the skin and by this route was found to have anti-arthritic activity. 65Zn was shown to be absorbed and excreted in the faeces (biliary excretion) after applying 65Zn-ZMG dermally to shaved dorsal skin of rats. ZMG showed consistent anti-arthritic activity in rats under conditions in which 2 gold drugs (aurothiomalate, Auranofin) exhibited variable effects, depending on the strain of rat. The role of zinc and its availability in chronic inflammation are discussed on the basis of these studies.

Animals↗

PubMed1990

Progressive cancellous bone loss in rats after adrenalectomy and oophorectomy.

Female Sprague-Dawley rats (n = 72), 6 months old, underwent either sham operation, oophorectomy, adrenalectomy, or combined oophorectomy and adrenalectomy (O&A). They were all maintained on normal saline ad libitum and 20 g/day 1.1% calcium chow. Nine weeks after operation, the trabecular bone volume of the distal femoral shaft was significantly lower (P less than 0.001) in the adrenalectomized (11.1%), oophorectomized (7.0%), and O&A (8.3%) animals than in sham-operated animals (19.8%). Eighteen weeks after operation, the trabecular bone volume in O&A animals had fallen to a mean of 3.8% (sham 17.0%), and the length of the femur had increased to 38.8 mm after O&A (sham 36.8 mm, P less than 0.01). O&A animals treated with 0.35 mg/kg/week nandrolone decanoate from 9 weeks postoperatively onward, had twice the femoral trabecular bone volume of untreated animals at 18 weeks (P less than 0.05). By contrast, no significant differences were found in vertebral body trabecular bone between any groups, including groups receiving treatment with androgens. We have found that, by 9 weeks after operation, adrenalectomy alone causes significant loss of metaphyseal trabecular bone, similar to the progressive loss seen after oophorectomy.

Adrenal Glands↗

PubMed1990

The cyclo-oxygenase inhibitor, piroxicam, enhances cytokine-induced lymphocyte proliferation in vitro and in vivo.

The effects of Piroxicam on the production and activity of lymphoproliferative cytokines (LC) produced by mononuclear phagocytes (MNP) were examined. In vitro, Piroxicam did not affect IL-1 induced thymocyte proliferation (LAF assay). However, the LAF activity from lipopolysaccharide (LPS)-treated MNP cultures was increased after Piroxicam (0.1-20 mumol/L) treatment. The increase in apparent LC activity was largely due to suppression of prostaglandin E2 (PGE2) production. Peripheral blood, spleen and thymus lymphocytes from animals predosed with Piroxicam (5 mg/kg per day for 3 days) synthesized more DNA than untreated mice (as measured by [3H]-thymidine uptake ex vivo). MNP from Piroxicam-treated animals produced significantly more LC. Piroxicam had similar effects in both inflamed and non-inflamed mice. Piroxicam and other non-steroidal anti-inflammatory drugs (NSAID) may therefore stimulate or modulate the immune functions requiring lymphoproliferation by suppressing the formation of PGE2, a natural inhibitor of both LC production and LC-induced lymphoproliferation.

Animals↗

PubMed1990

Prevention of adjuvant-induced cachexia in rats by cyclosporin A.

The changes in food intake and biochemistry following Freund's adjuvant (AJ)-induced inflammation in rats were investigated. Injection of AJ into rats resulted in a transient anorexia but a sustained decrease in body weight. Within 14 days, body weight decreased by 12% (P less than 0.05) and adipose tissue (retroperitoneal fat pads) decreased by more than 50%. Biochemical changes seen in association with the AJ-induced wasting included decreased plasma concentrations of triglyceride and cholesterol. Injection of cyclosporin-A (CS) (20 mg/kg) with the AJ decreased the anorexia, prevented the sustained loss of body weight and adipose tissue and reversed the effects on plasma triglyceride and cholesterol concentrations. Insulin concentrations were not significantly affected by the AJ or AJ/CS treatments. Peritoneal macrophages from AJ-treated rats produced 3-fold more tumour necrosis factor-alpha (cachectin) than control rats. This effect was not observed in rats treated with AJ plus CS. The results are consistent with CS preventing the release of cytokines which have anorectic and catabolic actions (IL-1, TNF), although there is also the possibility that CS has effects involving endocrine mechanisms.

Adipose Tissue↗

PubMed1990

1990 Volvo Award in experimental studies. Anulus tears and intervertebral disc degeneration. An experimental study using an animal model.

An animal model was developed to test the hypothesis that discrete peripheral tears within the anulus lead to secondary degenerative changes in other disc components. In 21 adult sheep, a cut was made in the left anterolateral anulus of three randomly selected lumbar discs. The cut was parallel and adjacent to the inferior end-plate, and had a controlled depth of 5 mm. This left the inner third of the anulus and the nucleus pulposus intact and closely reproduced the rim Lear lesion described by Schmorl. Animals were randomly allocated to different groups in relation to the length of time interval between operation and death, varying from 1 to 18 months. At death, the lumbar spine was cut into individual joint units and each disc sectioned into six parasagittal slabs. After observation of the slabs under the dissecting microscope, two of the six slabs, the one containing the anulus lesion and a contralateral, were processed for histology. The results of this study suggest that, despite the great care taken at operation to ensure that the inner anulus was left intact, progressive failure of the inner anulus was seen in all sheep and occurred in the majority of discs between 4 and 12 months after the operation. Although the outermost anulus showed the ability to heal, the defect induced by the cut led initially to deformation and bulging of the collagen bundles, and eventually to inner extension of the tear and complete failure. These findings suggest that discrete tears of the outer anulus may have a role in the formation of concentric clefts and in accelerating the development of radiating clefts. Peripheral tears of the anulus fibrosus therefore may play an important role in the degeneration of the intervertebral joint complex.

Animals↗

PubMed1990

Discitis after discography. The role of prophylactic antibiotics.

Discitis after discography is due to bacterial penetration into the intervertebral disc by a contaminated needle and has an incidence of 1% to 4%. We have examined the prophylactic role of cephazolin administered at the time of discography. An experimental study in sheep using radiographic contrast containing Staphylococcus epidermidis showed that either adding the antibiotic to the intradiscal suspension or giving it intravenously 30 minutes before intradiscal inoculation of bacteria prevented any radiographic, macroscopic or histological signs of discitis; all the intervertebral disc cultures were negative. In a prospective clinical study of 127 consecutive patients having lumbar discography, the injected contrast contained cephazolin 1 mg per ml. None of the patients developed clinical or radiographic signs of discitis. We recommend the use of a suitable broad spectrum antibiotic in a single prophylactic dose whenever the intervertebral disc is entered.

Animals↗

PubMed1990

Microfractures in coxarthrosis.

We examined the subchondral bone architecture of the femoral head in relation to trabecular microfracture. Three groups of femoral head specimens were studied. Twenty-eight specimens taken during hip replacement had grade III or IV arthrosis (70 +/- 8 years). From autopsy, 40 femoral heads were obtained, 18 in a group greater than 50 years of age (72 +/- 10 years) and 22 in a group less than 50 years of age (25 +/- 11 years). None of these 40 heads had worse than grade II arthrosis. Coronal slices of the femoral heads were macerated and examined under a dissecting microscope to count trabecular microfractures. For bone histomorphometry, blocks were taken from the subchondral principal compressive and tensile trabeculae. The bone volume, trabecular thickness, and marrow space were quantified. In the subchondral principal compressive region, the arthrotic group had more bone volume, thicker trabeculae, similar trabecular space, and trabecular microfractures when compared with the group greater than 50 years old. In the tensile region, there were no differences except for decreased trabecular microfracture number in the arthrotic group. With the thinnest trabeculae in the compressive region occurring in the greater than 50 years old group, the trabeculae of the younger age group have thinned with age, but with the onset of arthrosis, the thinning is overtaken by pathologic thickening of trabeculae.

Adult↗

PubMed1990

Age-related changes in femoral trabecular bone in arthrosis.

Age-related changes in the cancellous bone in selected regions of the proximal femur and iliac crest were assessed. An arthrosis group and a control cadaver group, partitioned into subjects younger and older than aged 50 years, were compared. The control group comprised 69 heads of femur and iliac crest samples. The arthrosis group comprised 28 consecutive heads of femur affected by primary arthrosis and an iliac crest biopsy taken during hip arthroplasty. Cancellous bone was sampled from four selected regions in the proximal femur. Histomorphometric estimates of percentage bone volume were determined using image analysis. In the young controls the bone volume was higher than that in the old controls for all the regions. In the arthrosis group the bone volume was higher than that of the old controls except for the subchondral principal tensile and medial to the greater trochanter regions. The old controls had regression of bone volume on age for the subchondral and medial principal compressive regions and the iliac crest. The arthrosis group had a minimal dependence of bone volume on age. Our study showed that primary arthrosis modulates the age dependence of bone volume in the proximal femur.

Adult↗

PubMed1990

Resurfacing hip arthroplasty. Classification of loosening and the role of prosthesis wear particles.

Operative grading of loosening and histologic examination of the periprosthetic tissues and the femoral and acetabular bone-cement interfaces were undertaken in 72 revised resurfacing hip arthroplasties. By correlating the degree of macroscopic and microscopic loosening at the bone-cement interface, a classification of the stages of loosening at the bone-cement interface was devised. Examination of the femoral bone-cement interface of solidly fixed prosthesis components has demonstrated the presence of polyethylene wear particles and a macrophage response at the interface prior to loosening. This suggests that wear particles may migrate along bone-cement interfaces that are both macroscopically and microscopically solid, and emphasizes the important role of wear particles in prosthesis loosening.

Adult↗

PubMed1989

Effect of mitogen and lymphokine stimulation on proteoglycan synthesis by lymphocytes.

The ability of mouse thymocytes and peripheral blood lymphocytes from rats to synthesize and secrete proteoglycans in the presence of a variety of mitogens and lymphokines was studied in vitro, and it was confirmed that such lymphocytes synthesize and secrete significant quantities of proteoglycans. Mitogenic stimulation of the cells with phytohaemagglutanin (PHA) induced a fourfold increase in proteoglycan synthesis; stimulation with interleukin-1 stimulated proteoglycan synthesis up to fivefold. Proteoglycan synthesis could also be stimulated by culturing the cells in the presence of interleukin-2. To determine if this response was related to cell proliferation, the cells were cultured in the presence of PHA and either cyclosporine or prostaglandin E2, two agents that inhibit lymphocyte proliferation. Under these conditions, proteoglycan synthesis remained elevated, indicating that this effect may be independent of cell proliferation. Chemical analysis of the proteoglycans indicated them to be composed of chondroitin sulfate and heparan sulfate. Their molecular size was small compared with cartilage proteoglycans but similar to the small dermatan sulfate proteoglycans synthesized by fibroblasts. On the basis of molecular size, three proteoglycan population were identified, and their relative proportions were altered by mitogenic stimulation of the cells. Taken together, these findings imply that proteoglycan synthesis is intimately associated with lymphocyte activation and may be related to cellular function in immune responses.

Animals↗