Biomedical subjects

Douglas J Coster

Publications and source records attributed to Douglas J Coster.

7 recordsLinked to original sources

PubMed2004

Is directed donation misguided?

The worldwide shortage of organs and tissue for transplant has led to many ethical discussions involving restrictions concerning organ and tissue donation, including living donations and payment for donation. Efforts are being made to increase the donor pool; however, it is timely to ask whether moral decisions such as the rejection of directed donations are defensible. In this Clinical Conundrum, six specialists delve into the ethical and practical issues surrounding directed donation of human organs and tissues with particular reference to its implications in the field of ophthalmology.

Cornea↗

PubMed2004

A practical approach to interpretation of corneal specimens.

Corneal specimens form only a small part of the routine practice for most histopathologists but their assessment often requires considerable effort and specialized knowledge. The most common corneal specimens, full-thickness corneal discs and corneal biopsies, are discussed in this review. Corneal discs removed at keratoplasty are non-urgent specimens, as definitive treatment has already been undertaken, and while the pathologic diagnosis may change the prognosis for the graft, it rarely affects immediate treatment. Accurate diagnosis is still important, and will affect counseling of the patient, but referral to a colleague with a special interest is possible if necessary. Conversely, small partial-thickness corneal biopsies, which are mostly undertaken for culture negative keratitis with underlying suspected infection, are very urgent. Infectious keratitis can follow an extremely aggressive course, resulting in destruction of the cornea within hours. Accurate diagnosis is imperative. Due to the urgency of such specimens and the importance of diagnosis for immediate treatment, referral is not usually possible. It is the role of the pathologist to make optimal use of a small specimen to reach the relevant diagnosis in the minimum space of time.

Biopsy↗

PubMed2004

Gene therapy approaches to prolonging corneal allograft survival.

Irreversible immunological rejection is the major cause of human corneal allograft failure and occurs despite the use of topical glucocorticoid immunosuppression. Systemic pharmacological interventions have not found widespread favour in corneal transplantation because of associated morbidities and inadequate demonstration of efficacy. Gene therapy offers tantalising prospects for improving corneal allograft survival, especially in those recipients at high risk of graft rejection. Donor corneas can be gene-modified ex vivo, while in storage prior to implantation, and the relative isolation of the transplanted cornea from the circulation decreases the risk of potential systemic complications. A wide variety of vectors have been found suitable for gene transfer to the cornea. The mechanisms involved in corneal graft rejection have been placed on a relatively secure footing over the past decade and in consequence a number of transgenes with promise for modulating rejection have been identified. However, relatively few studies have thus far demonstrated significant prolongation of corneal allograft survival after gene transfer to the donor cornea. In these instances, the therapeutic protein almost certainly acted at a proximal level in the afferent immune response, within the ocular environs.

Animals↗

PubMed2003

The potential of antibody-based immunosuppressive agents for corneal transplantation.

Corneal transplantation is a sight-restorative procedure but its success is limited by irreversible graft rejection, which accounts for up to 50 per cent of failures. The normal eye is an immune-privileged site. Multiple mechanisms maintain ocular privilege, including the blood-eye barrier, the lack of blood vessels and lymphatics in the normal cornea, the relative paucity of mature antigen-presenting cells in the central cornea, the presence of immunomodulatory factors in ocular fluids, and the constitutive expressive of CD95L (Fas ligand) within the eye. However, privilege can be eroded by the sequelae of inflammation and neovascularization. Corneal graft rejection in humans is currently suppressed with topical glucocorticosteroids, which are moderately effective. Systemically administered immunosuppressive therapy is of limited efficacy and may be accompanied by unacceptable morbidity. Alternative therapies are needed to improve outcomes. Corneal graft rejection is primarily a cell-mediated response controlled by the CD4+ T cell, and thus CD4 and costimulatory molecule blockade are appealing targets for new therapeutic interventions. A number of monoclonal antibodies have shown promise as immunosuppressants to prolong corneal graft survival in experimental animal models, and may eventually prove to be useful adjuncts to corticosteroids.

Antibodies, Monoclonal↗

PubMed2003

Cataract surgery and changes in quality of life measures.

BACKGROUND: This study examines whether quality of life measured with non-disease specific instruments is altered by cataract surgery and whether the effect is modulated by the presence of ocular comorbidity or other non-ocular issues. METHODS: Thirteen patients were assessed pre- and at three months post-cataract surgery. Visual disability was measured with the Visual Disability Assessment. Quality of life was measured using two established generic instruments: the Cantril Ladder and the Profile of Mood States (POMS). Subjects were also asked to report any events that may have influenced their quality of life in the three months after surgery. RESULTS: Visual acuity and visual disability were significantly improved by surgery (p < 0.01). Cantril Ladder score was significantly improved after surgery (p = 0.04). The POMS score improved significantly after surgery, only when cases with ocular comorbidity were excluded (p = 0.04). Two cases had a large deterioration in POMS score that was attributable in one case, to the death of a partner and in the other (a patient with severe glaucoma) to depression from the realisation that there was no further potential for visual improvement. DISCUSSION: Quality of life can be measurably improved by cataract surgery. However, this is less likely if ocular comorbidity is present. The use of generic instruments for outcome studies increases the likely influence of external factors on quality of life measures. Disease specific instruments, such as the Visual Disability Assessment, should be used wherever possible in outcomes research.

Aged↗

PubMed2002

An economical 20 litre bench-top fermenter.

We describe an economical 20 litre bench-top fermenter suitable for production of recombinant antibody fragments in bacterial expression systems. The bacterial culture contained within a polycarbonate carboy is mixed (400-600 rpm) and aerated (1 vessel vol./min) by a high-shear radial flow impeller mounted on a hollow stainless steel shaft, through which pressurised air is pumped. Air is dispersed as fine bubbles into the culture medium by the turbine impeller, without the need for a porous sparger. A stainless steel baffle stabilised by a gliding counterweight increases mixing. The components can easily be disassembled for cleaning and sterilisation. Temperature (range 20-37 degrees C) and pH (range 7.0-7.5) are controlled manually. Using the apparatus, it proved possible to achieve Escherichia coli cell culture densities equivalent to an optical density at 600 nm (OD(600)) of 30-32, compared with OD(600) 4-6 in shake flasks. A yield of 40 mg/litre/day of a recombinant antibody fragment was obtained with the fermenter, which was 15-fold more than the yield of 2.5mg/litre/day achieved in shake flasks. The fermenter may be particularly suited for research purposes.

Antibodies↗

PubMed2002

Effect of immunosuppression on outcome measures in a model of rat limbal transplantation.

PURPOSE: To examine the effect of immunosuppression with intramuscularly injected cyclosporine and topical corticosteroid on limbal allograft survival in a new model in the inbred rat. METHODS: Orthotopic limbal tissue harvested from male Fischer 344 (isografts) or male Wistar-Firth donors (allografts) was sutured into superior and inferior lamellar excision sites in female recipient Fischer 344 rats. Grafts were examined clinically for at least 55 days. Superficial epithelial cells were sampled weekly, and the DNA extracted and probed for the male-specific gene Sry by polymerase chain reaction. Recipients were killed at established intervals for immunohistochemistry. Graft-recipient animals were randomly assigned to receive either intramuscular cyclosporine plus topical prednisolone phosphate or vehicle for 4 weeks from the time of transplantation. RESULTS: Isografts survived for a median of more than 55 days. Allografts underwent clinical rejection at a median of 6 to 7 days after grafting. Acutely rejecting allografts showed a dense mononuclear infiltrate consisting of activated CD4(+) and CD8(+) T cells with some macrophages. Genomic Sry was usually detectable in cells sampled from the ocular surface for more than 55 days in isografts, but not beyond 7 days in allografts. Immunosuppression prolonged allograft survival significantly, as assessed clinically, but did not prolong donor cell survival on the ocular surface, as assessed by detection of genomic Sry. CONCLUSIONS: A robust model of limbal transplantation was developed in the rat. Isografts survived for the long term, whereas allografts underwent rapid rejection. Although clinical allograft survival was prolonged to a modest extent by immunosuppression, donor cell survival on the ocular surface was not improved.

Administration, Topical↗