Biomedical subjects

A R Harvey

Publications and source records attributed to A R Harvey.

At least 37 records · Page 2Linked to original sources

PubMed2001

Do rheumatologists recognize their patients' work-related problems?

OBJECTIVE: The question addressed in this pilot study was 'Does the addition of an occupational health physiotherapist offering early vocational assessment influence the management of rheumatology patients (clinically and related to the workplace)?' METHOD: Sequential vocational assessments were offered to 78 subjects with rheumatological complaints of more than 1 yr duration experiencing difficulties in working. The findings from the vocational assessments were fed back to rheumatologists. Where necessary and acceptable, workplace interventions were made and the Employment Service's Access to Work scheme was utilized to address the employment problems found. RESULTS: The intervention vocational assessments trebled the number of subjects seeing a Disability Employment Adviser (17% before the study, a further 37% during it). High levels of satisfaction were reported for interventions made at work. Some important changes to the management of some patients by a few doctors were made, but information from the vocational assessments did not reach them reliably in a number of cases. CONCLUSION: An unmet need for advice and workplace aids and equipment was identified. Vocational assessment by a practitioner with clinical knowledge, ergonomic and workplace experience proved helpful to patients in this pilot study. Without vocational assessment, the hospital-based team rarely identified what were often remediable, work problems and appeared unaware of the appropriate referral route for this group of patients. Rheumatologists may need to expand their management to include consideration of work issues to ensure that their patients are referred early for appropriate ergonomic intervention when required. Further study is required to help facilitate easy identification in the clinical setting of patients with problems at work.

Adult↗

PubMed2000

CNTF promotes the regrowth of retinal ganglion cell axons into murine peripheral nerve grafts.

Autologous peripheral nerves were transplanted onto transected optic nerves of adult mice. We examined whether intraocular CNTF injections increased retinal ganglion cell (RGC) axon regeneration, and what types of RGCs regrew axons into grafts. After temporal CNTF eye injections there were more fluorogold-labelled regenerating RGCs (mean +/- s.e.m. 342+/-113.1; n=6) than in sham eye-injected mice (133+/-27.6; n=8). Greater numbers of regenerating RGCs (1198+/-367.6; n=6) were seen in mice receiving both nasal and temporal CNTF injections. The range of soma areas in regenerate and normal retinas was similar but the average size of regenerating RGCs was greater (212 microm2 vs 111 microm2). Most regenerating RGCs had large dendritic fields. The data suggest a heterogeneous response to axotomy in adult mice, large RGCs preferentially regrowing axons into PN grafts.

Animals↗

PubMed2000

NT-4/5 reduces cell death in inner nuclear as well as ganglion cell layers in neonatal rat retina.

Using the TUNEL method, we examined the effect of intraocular NT-4/5 injections on cell death in ganglion and non-ganglion cell layers in 5-day-old rat retinas. NT-4/5 reduced the level of naturally occurring cell death in all retinal layers. Twenty-four hours after superior colliculus (SC) lesions there was a significant increase in the density of TUNEL+ profiles in the RGC layer (6.43/mm2 in normal vs (8.89/mm2 after lesions) which was ameliorated by intraocular NT-4/5 injections (8.79/mm2). Surprisingly, after SC ablation a significant increase in TUNEL+ profiles was also seen in non-ganglion cell layers (52.25/mm2 in normal vs 89.35/mm2 after lesions), mostly in the developing inner nuclear layer. Death in non-ganglion cell layers was also significantly reduced (43.09/mm2) after NT-4/5 eye injections.

Animals↗

PubMed2000

Hartshill rectangle: failure of spinal stabilisation in acute spinal cord injury.

A high rate of failure of the internal fixation of unstable spinal fractures in complete cord injured patients was noted in patients referred to the Salisbury Spinal Centre who had been stabilised with a Hartshill rectangle. This prompted a review of the operative notes, radiographs and clinical outcomes of all patients referred to the centre with a Hartshill rectangle in situ. All patients identified with a complete spinal cord injury and Hartshill rectangle were identified. Forty-three such patients referred from 13 different centres were found. Pre- and postoperative radiographs were assessed for fracture pattern and for spinal correction. Operative outcome in terms of pain and complications relating to surgery were identified. The most recent radiographs were assessed for signs of loss of reduction or stabilisation. Follow-up averaged 84 months (range 36-132 months). Of the 43 identified patients, 19 were found to have unsatisfactory stabilisation. Persistent pain, broken implants and worsening kyphosis were the main complications. The failure to use bone graft at the time of stabilisation was significantly (P < 0.001) related to risk of failure. The application and use of the Hartshill is not a technically challenging procedure; however, if the system is to be used, it must be used correctly. Failure to correctly apply the rectangle and to use bone graft will lead to an unacceptably high rate of failure.

Adolescent↗

PubMed2000

A gas filled intradural cyst associated with disc degeneration.

A case of a lumbar intradural, extramedullary gas filled cyst is described. This was associated with degenerative disc disease and presented with radicular signs and symptoms. The radiological differential diagnosis of such a mass includes infection and tumours. The association of intradural gas with degenerative disc disease is previously reported. This case further illustrates the association of degenerative disc disease with an intradural gas filled cyst and provides an interesting radiological differential diagnosis for an extramedullary intradural mass.

Central Nervous System Diseases↗

PubMed1999

Retinal axon regeneration in peripheral nerve, tectal, and muscle grafts in adult rats.

This study examined whether prior regenerative growth through peripheral nerve (PN) bridging grafts influenced the specificity with which lesioned adult rat retinal ganglion cell (RGC) axons grew into co-grafts of developing target tissue (fetal superior colliculus). Growth into nontarget (muscle) tissue was also examined. Autologous PN was grafted onto the transected optic nerve. After 14 days, the distal ends of the PNs were placed next to, or inserted into, embryonic tectal tissue or into autologous muscle grafts placed in frontal cortex cavities. Host retinal projections were examined 3-8 months later using anterograde and retrograde tracing techniques. In rats in which there was good apposition between PN and tectal tissue, small numbers of RGC axons were observed growing into the tectal grafts (maximum distance of 180 microm). No evidence of specific innervation of appropriate target regions within tectal grafts was detected, even though such regions (identified by acetylcholinesterase histochemistry) were often located close to the PN grafts. In rats with PN/muscle co-grafts, the extent of retinal axon outgrowth was greater (up to 465 microm from the PN tip) and labelled profiles that resembled motor endplates were seen contacting muscle fibres. Previous studies have shown that spontaneously regenerating RGC axons consistently and selectively innervate appropriate target areas in fetal tectal tissue grafted directly into optic tract lesion cavities. Together, the data suggest that exposure to a PN environment may have reduced the extent of adult retinal axon growth into fetal tectal transplants and affected the way regenerating axons responded to specific developmental cues expressed by target cells in the co-grafted tissue.

Animals↗

PubMed1999

Astrocytes, oligodendroglia, extracellular space volume and geometry in rat fetal brain grafts.

Fetal neocortex or tectum transplanted to the midbrain or cortex of newborn rats develops various degrees of gliosis, i.e. increased numbers of hypertrophied, glial fibrillary acidic protein-positive astrocytes. In addition, there were patches or bundles of myelinated fibres positive for the oligodendrocyte and central myelin marker Rip, and increased levels of extracellular matrix molecules. Three diffusion parameters--extracellular space volume fraction alpha (alpha = extracellular volume/total tissue volume), tortuosity lambda (lambda = square root(D/ADC), where D is the free and ADC is the apparent tetramethylammonium diffusion coefficient) and non-specific uptake k'--were determined in vivo from extracellular concentration-time profiles of tetramethylammonium. Grafts were subsequently processed immunohistochemically to compare diffusion measurements with graft morphology. Comparisons were made between the diffusion parameters of host cortex and corpus callosum, fetal cortical or tectal tissue transplanted to host midbrain ("C- and T-grafts") and fetal cortical tissue transplanted to host cortex ("cortex-to-cortex" or C-C-grafts). In host cortex, alpha ranged from 0.20 +/- 0.01 (layer V) to 0.21 +/- 0.01 (layers III, IV and VI) and lambda from 1.59 +/- 0.03 (layer VI) to 1.64 +/- 0.02 (layer III) (mean +/- S.E.M., n = 15). Much higher values were found in "young" C-grafts (81-150 days post-transplantation), where alpha = 0.34 +/- 0.01 and lambda = 1.78 +/- 0.03 (n = 13), as well as in T-grafts, where alpha = 0.29 +/- 0.02 and lambda = 1.85 +/- 0.04 (n = 7). Further analysis revealed that diffusion in grafts was anisotropic and more hindered than in host cortex. The heterogeneity of diffusion parameters correlated with the structural heterogeneity of the neuropil, with the highest values of alpha in gray matter and the highest values of lambda in white matter bundles. Compared to "young" C-grafts, in "old" C-grafts (one year post-transplantation) both alpha and lambda were significantly lower, and there was a clear decrease in glial fibrillary acidic protein immunoreactivity throughout the grafted tissue. In C-C-grafts, alpha and lambda varied with the degree of graft incorporation into host tissue, but on average they were significantly lower (alpha = 0.24 +/- 0.01 and lambda = 1.66 +/- 0.02, n = 8) than in young C- and T-grafts. Well-incorporated grafts revealed less astrogliosis, and alpha and lambda values were not significantly higher than those in normal host cortex. The observed changes in extracellular space diffusion parameters could affect the movement and accumulation of neuroactive substances and thus impact upon neuron-glia communication, synaptic and extrasynaptic transmission in the grafts. The potential relevance of these observations to human neuropathological conditions associated with acute or chronic astrogliosis is considered.

Animals↗

PubMed1999

Neural tissue formation within porous hydrogels implanted in brain and spinal cord lesions: ultrastructural, immunohistochemical, and diffusion studies.

A biocompatible heterogeneous hydrogel of poly [N-(2-hydroxypropyl) methacrylamide] (PHPMA), was evaluated for its ability to promote tissue repair and enhance axonal regrowth across lesion cavities in the brain and spinal cord in adult and juvenile (P17 P21) rats. Incorporation of PHPMA hydrogels into surrounding host tissue was examined at the ultrastructural level and using immunohistochemical techniques. In addition, and in parallel to these studies, diffusion parameters (volume fraction and tortuosity of the gel network) of the PHPMA hydrogels were evaluated pre- to postimplantation using an in vivo real-time iontophoretic method. The polymer hydrogels were able to bridge tissue defects created in the brain or spinal cord, and supported cellular ingrowth, angiogenesis, and axonogenesis within the structure of the polymer network. As a result, a reparative tissue grew within the porous structure of the gel, composed of glial cells, blood vessels, axons and dendrites, and extracellular biological matrices, such as laminin and/or collagen. Consistent with matrix deposition and tissue formation within the porous structure of the PHPMA hydrogels, there were measurable changes in the diffusion characteristics of the polymers. Extracellular space volume decreased and tortuosity increased within implanted hydrogels, attaining values similar to that seen in developing neural tissue. PHPMA polymer hydrogel matrices thus show neuroinductive and neuroconductive properties. They have the potential to repair tissue defects in the central nervous system by replacing lost tissue and by promoting the formation of a histotypic tissue matrix that facilitates and supports regenerative axonal growth. () ()

Animals↗

PubMed1998

The effects of central administration of neurotrophins or transplants of fetal tectal tissue on retinal ganglion cell survival following removal of the superior colliculus in neonatal rats.

In neonatal rats, intraocular injections of brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT-4/5) enhance the survival of retinal ganglion cells (RGCs) following superior colliculus (SC) ablation [Q. Cui, A.R. Harvey, At least two mechanisms are involved in the death of retinal ganglion cells following target ablation in neonatal rats, J. Neurosci., 15, 1995, pp. 8143-8155.]. The aim of the present study was to determine if: (i) fetal tectal tissue grafted into the lesion site, or (ii) neurotrophins applied centrally to the injured SC, also decreased lesion-induced RGC death. Nuclei of tectally projecting RGCs were identified by injecting diamidino yellow (DY) into the left SC of 2-day-old (P2) Wistar rats. Injected SCs were lesioned at P4. In some animals, embryonic (E16) tectal tissue was then implanted into the lesion cavity; host rats were perfused 24 h or 20 days later. In short-term (24-h) studies, the number of DY-labelled pyknotic profiles was compared to the number of normal DY-labelled RGCs in retinal wholemounts (right eyes). The proportion of dying RGCs in animals with grafts (10.7%, n = 17) was not significantly different from lesion-only rats (13.2%, n = 26). Nonetheless, the long-term (20-day) study showed that, in most rats, fetal tectal tissue survived in the lesion cavity and in some cases, the grafts received host retinal input. In another group, different doses of BDNF or NT-4/5 were applied to the SC after P4 tectal lesions. Rats were perfused 24 h later and the number of pyknotic vs. normal DY-labelled RGCs was determined. Initial trials in which SC lesions were filled with gelfoam soaked in BDNF or NT-4/5 were unsuccessful; however, RGC death was reduced (p < 0.05, Dunnett's test) in rats that received gelfoam implants as well as focal neurotrophin injections into SC rostral to the lesion. The lowest pyknotic rate in individual animals from the BDNF and NT-4/5 groups was 2.41% and 2.01%, respectively. Overall, the proportion of dying RGCs was 7.0% (n = 8) for BDNF and 7.4% (n = 17) for NT-4/5 treated rats. Normal RGC densities were also significantly higher in these animals. NT-4/5 topically applied to the posterior surface of the eye did not reduce RGC death. The data show that the viability of injured neonatal RGCs is increased by specific retrograde neurotrophin-mediated survival signals which can be activated from the SC.

Administration, Topical↗

PubMed1997

Fate of adult neural precursors grafted to adult cortex monitored with a Y-chromosome marker.

Freshly dissected and dissociated subventricular zone cells from adult male mice were transplanted into the right cerebral cortex of adult female mice. Host mice were perfused 3 or 7 weeks later. To detect donor male cells, paraffin sections (10 microm) were hybridized in situ with a Y-chromosome-specific probe. Some hybridized sections were also immunostained with antibodies against glial fibrillary acidic protein (GFAP), NeuN or beta-tubulin. Grafted cells were identified in 80% of host female brains; they were found in both grey and white matter and were located close to the initial injection site. Double-labelling studies showed that, of the surviving cells containing hybridized male nuclei, 5-10% expressed a glial (GFAP) marker and 6-7% expressed neuronal (NeuN or beta-tubulin) markers.

Animals↗

PubMed1997

A comparison of postlesion growth of retinotectal and corticotectal axons after superior colliculus transections in neonatal rats.

We examined, in neonatal rats, the postinjury response of two different axonal systems that project to a common target area in the visual system. Transections across the rostral part of the left superior colliculus (SC) were made in 2- or 6-day-old rats (P2, P6). Lesioned animals were randomly selected into short- or long-term groups. The short-term group was used to determine the efficacy of the lesion technique; 2-6 days after transections, right (contralateral) eyes were injected with horseradish peroxidase (HRP). Complete deafferentation of the SC was achieved in 73% of P2 (n = 22) and 53% of P6 (n = 10) short-term animals. In the long-term group (examined 2-7 months after transection), retinotectal and corticotectal projections were assessed in each animal by using [3H]proline and wheat germ agglutin-HRP, respectively. Examination of a series of sagittal sections revealed that the cut had extended across the entire SC in 63% of P2 (n = 19) and 55% of P6 (n = 12) long-term rats. Despite this, retinal and cortical axons were seen in appropriate layers in postlesion SC in all P2 lesioned animals. Cortical projections caudal to the cut were seen in all P6 rats; however, in these animals, the retinal projection was sparse and not always present. Differences in lesion geometry led to consistent differences in the pattern and extent of ingrowth of retinal and cortical axons into postlesion SC neuropil. The two axonal populations also followed different paths as they grew between prelesion and postlesion SC. It is likely that a number of factors influenced the patterns of postlesion growth, including the relative maturity of the axons and the neuropil into which they were growing. There was also, however, clear evidence of competitive interactions between retinal and cortical axons in postlesion SC that consistently led to greater than normal segregation of the two populations and hence restricted their terminal distributions.

Animals↗

PubMed1997

The status and organization of astrocytes, oligodendroglia and microglia in grafts of fetal rat cerebral cortex.

Immunohistochemical methods were used to study the status and organization of astrocytes, oligodendroglia and microglia in fetal cerebral cortical tissue grafted on to the dorsal surface of the midbrain in newborn host rats. Grafts were examined 1-6 months posttransplantation. All grafts contained large numbers of hypertrophied, intensely glial fibrillary acidic protein-positive astrocytes. Microglia were also activated, displaying slightly increased levels of OX-42 immunoreactivity. The grafts consisted of lobules of gray matter which were separated by bands of myelinated fibres associated with large numbers of Rip-positive oligodendroglia. These glial cells had a relatively normal morphology. The density of astrocytes and microglia was reduced in these white matter-like regions. In association with chronic changes in glial reactivity, transplants also expressed increased levels of chondroitin sulphate proteoglycans (CS-56 antibody). The observed changes in glial cell phenotype and extracellular matrix in cortical transplants are likely to affect neuronal physiology and connectivity in a number of ways, and highlight the importance of studying both glia and neurons in order to gain a more comprehensive picture of the long-term functional potential of fetal brain grafts.

Animals↗

PubMed1997

Hydrogels containing peptide or aminosugar sequences implanted into the rat brain: influence on cellular migration and axonal growth.

Biocompatible polymer matrices for implantation into lesion sites in the brain were synthesized by incorporating peptide or aminosugar sequences into N-(2-hydroxypropyl)methacrylamide (HPMA) hydrogels. RGD peptide sequences were chemically linked to the hydrogel backbone via a glycylglycine spacer; aminosugars were glucosamine (NHGlc) or N-acetylglucosamine residues. Unmodified or sequence containing HPMA hydrogels were implanted into the lesioned optic tract or cerebral cortex of juvenile (17- to 19-day-old) or adult rat brains, respectively. After 10-12 months host animals were perfused and the brains were processed for immunohistochemistry using antibodies to neurofilaments (RT97), laminin, glial fibrillary acidic protein (GFAP), carbonic anhydrase II (CAII), S100 protein, macrophages (ED1), and myelin basic protein (MBP). Unmodified (control) HPMA hydrogels contained no cellular infiltration or axonal growth. Peptide (RGD)- and aminosugar-modified hydrogels showed increased adhesion properties with host neural tissue, were vascularized, and were infiltrated by host nonneuronal cells. Astrocytes (GFAP+) and macrophages (ED1(+)) were the major cell types seen within modified HPMA hydrogels, the largest numbers being found in RGD-containing polymers. CAII+ oligodendroglia were not seen within any of the hydrogel matrices. RT97(+)/MBP- axons grew into both the RGD and NHGlc hydrogel matrices for small distances. The number of axons was greatest in hydrogels implanted into cerebral cortex but in both cortex and optic tract implants the highest density of axons was seen in polymers containing RGD. The findings of this study are discussed in the context of CNS tissue replacement and the construction of bioactive scaffolds to promote regenerative axonal growth across areas of injury in the brain and spinal cord.

Animals↗

PubMed1997

A comprehensive Afrocentric rites of passage program for black male adolescents.

The health consequences for African American male teenagers of living in high-risk environments are devastating. Given the existence of cultural barriers to health services use, culturally proficient programs that can engage African American male youths in preventive interventions and primary care are urgently needed. This article reviews the health status of African American male adolescents, noting that the leading health problems are preventable. The article then discusses two frameworks that are of value in social work practice with African American populations, cultural competence and empowerment; reviews of Afrocentric theory and Afrocentric social work; and describes a culturally proficient, Afrocentric program for African American male adolescents. Health social workers can take steps to increase their own cultural competence and that of the health care organizations in which they work.

Adolescent↗

PubMed1997

In vitro assessment of the biological activity of basic fibroblast growth factor released from various polymers and biomatrices.

The kinetics of controlled release of basic fibroblast growth factor (bFGF) from polymers (sutures, polycarbonate, Hydron, and Elvax), biopolymers (alginate), and biomatrices (lens capsules), and conditions for storage of bFGF (temperature, plastic type, heparin) were evaluated in vitro. Tissue culture proliferation bioassays with 3T3 fibroblasts, showed that only lens capsules with bFGF had a sustained release of bFGF for up to three weeks. The other materials released all of the 'bound' bFGF with two hours or produced an inflammatory response in vivo. Therefore, the lens tissue had the most potential for controlled long-term delivery of bFGF in vivo. These studies emphasise the importance of in vitro analysis of release kinetics of growth factors from a range of materials as a basis for potential in vivo applications.

3T3 Cells↗

PubMed1996

Cultured rat neuronal and glial cells entrapped within hydrogel polymer matrices: a potential tool for neural tissue replacement.

Cultured Schwann cells, neonatal astrocytes or cells dissociated from embryonic cerebral hemispheres were dispersed within poly-[N-(2-hydroxypropyl)-methacrylamide]-based hydrogel matrices by gel entrapment and maintained in vitro for 1-6 days. Glial cells were pre-labelled with Hoechst 33342. Cell differentiation and viability were studied by immunocytochemistry. Up to 15% of Schwann cells initially entrapped within the polymer matrices were immunopositive for the low affinity nerve growth factor receptor, S100, glial fibrillary acidic protein (GFAP) and laminin; up to 10% of pre-labelled astrocytes were immunopositive for GFAP and laminin. Embryonic neurons displayed immunostaining for neurofilaments. Hydrogels containing entrapped Schwann cells were implanted into the rat neocortex. These polymers supported cellular and axonal ingrowth within parts of the polymer matrix.

Animals↗

PubMed1996

Neural tissue engineering: from polymer to biohybrid organs.

This investigation reports on the immobilization of neuronal and glial cells (Schwann cells and astrocytes) within N-(2-hydroxypropyl) methacrylamide (HPMA) polymer hydrogels for the production of cell-based polymer hybrid devices. Cells were included within HPMA polymer networks by gel-entrapment, and these biogels were maintained in vitro for up to 6 days. Cell viability and differentiation were studied using immunocytochemical methods and image analysis techniques. The polymer structure and its relationships with cells were examined by scanning electron microscopy. A proportion of the cell population was viable, expressing its own antigenic profile throughout the period of gel incubation, as cells do in conventional culture conditions, and some cells exhibited behaviour such as spreading or process outgrowth and secretion of laminin. The result of the present study allows us to envisage tissue replacement in the central nervous system by means of such cell-based polymer constructs.

Animals↗

PubMed1995

Radial and tangential dispersion patterns in the mouse retina are cell-class specific.

The retina is derived from a pseudostratified germinal zone in which the relative position of a progenitor cell is believed to determine the position of the progeny aligned in the radial axis. Such a developmental mechanism would ensure that radial arrays of cells which comprise functional units in the mature central nervous system are also clonally related. The present study has tested this hypothesis by using X chromosome-inactivation transgenic mosaic mice. We report that the retina shows a conspicuous distinction for clonally related neuroblasts of different laminar and functional fates: the rod photoreceptor, Müller, and bipolar cells are aligned in the radial axis, whereas the cone photoreceptor, horizontal, amacrine, and ganglion cells are tangentially displaced with respect to them. These results indicate that the dispersion of cell classes across the retinal surface is differentially constrained. Some classes of retinal neuroblast exhibit a significant tangential, as well as radial, component in their dispersion from the germinal zone, whereas others disperse only in the radial dimension. Consequently, the majority of radial columns within the mature retina must be derived from multiple progenitors. Because the cone photoreceptor, horizontal, amacrine, and ganglion cells establish nonrandom matrices in their cellular distributions within the respective retinal layers, tangential dispersion may be the means by which these matrices are constructed.

Animals↗