Biomedical subjects

W John Armitage

Publications and source records attributed to W John Armitage.

5 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↗

PubMed2003

Prospective, randomized clinical and endothelial evaluation of 2 storage times for cornea donor tissue in organ culture at 31 degrees C.

OBJECTIVE: To compare the endothelial and clinical outcome of penetrating keratoplasty with corneas stored in organ culture for up to 12 days (5-12 days; group 1) or more than 21 days (21-24 days; group 2). METHODS: We conducted a controlled double-masked trial. Storage durations were randomly assigned to the paired corneas, and endothelial cell density (ECD) was measured at the start and end of organ culture. Patients with a low rejection risk and preoperative ECD within the reference range were randomly assigned to 1 of the 2 groups and underwent an 8.25-mm penetrating keratoplasty (n = 25 pairs). Follow-up at day 5 and months 1, 6, and 12 included central ECD, morphometry, graft transparency, visual acuity, pachymetry, and complications. The main outcome measure was the central ECD at month 12. RESULTS: At the end of organ culture, ECD of the group 1 corneas was higher by 273 cells/mm2 (95% confidence interval [CI], 178-368; P<.001). One year after penetrating keratoplasty, the group 1 ECD was still comparably higher by 227 cells/mm2 (95% CI, 43-411; P =.02). Graft transparency, pachymetry, and complication rate did not differ at any time. In group 1, visual acuity was better at month 1. CONCLUSIONS: Shorter organ culture allows delivery of corneas with higher ECD. Recipients with ECD within the reference range and low rejection risk retain this initial benefit 1 year postoperatively. The higher endothelial cell capital may prevent or delay late endothelial failure, the leading cause of graft failure in these recipients. We therefore prefer short-term storage for such recipients.

Adult↗

PubMed2003

Cryopreservation of cornea: a low cooling rate improves functional survival of endothelium after freezing and thawing.

AIM: To investigate the influence of low cooling rates on endothelial function and morphology of corneas frozen with propane-1,2-diol (PROH). METHODS: Rabbit corneas, mounted on support rings, were exposed to 1.4mol/l (10% v/v) PROH, seeded to initiate freezing, and cooled at 0.2 or 1 degrees C/min to -80 degrees C. Corneas were frozen immersed in liquid or suspended in air. After being held overnight in liquid nitrogen, corneas were warmed at 1 or 20 degrees C/min. After stepwise removal of the cryoprotectant, the ability of the endothelium actively to control corneal hydration was monitored during normothermic perfusion. Morphology was assessed after staining with trypan blue and alizarin red S, and by specular microscopy during perfusion. RESULTS: Functional survival was achieved only after slow cooling (0.2 degrees C/min) with the cornea immersed in the cryoprotectant medium, and rapid warming (20 degrees C/min). These conditions also gave the best morphology after freezing and thawing. CONCLUSION: Cooling rates lower than those typically applied to cornea improved functional survival of the endothelium. This result is in accord with previous observations showing the benefit of low cooling rates for cell monolayers [CryoLetters 17 (1996) 213-218].

Animals↗

PubMed2003

Predicting endothelial cell loss and long-term corneal graft survival.

PURPOSE: To evaluate a biexponential decay model for describing the loss of corneal endothelial cells with age as well as the increased loss of cells after cataract surgery and penetrating keratoplasty. METHODS: Data from previous studies were identified and the sum of two exponentials, d = p. exp(-at) + q. exp(-bt) (where d is cell density at time t, p and q are constants the sum of which is equal to the initial cell density, and a and b are exponential rate constants), fitted to each data set by a nonlinear least-squares algorithm. Goodness of fit was indicated by the residual standard deviation. Half times were calculated from the exponential rate constants. RESULTS: The model identified in each instance a rapid and a slow component to the cell loss. The half time for the slow component of the loss with age was 224 years, underlining the excess endothelial capacity in normal eyes. After surgery, the rapid component of the cell loss was probably due to surgical trauma and, after penetrating keratoplasty, cell-mediated rejection and other complications. The half times of the slow component were only 26 years after cataract surgery and 21 years after penetrating keratoplasty. DISCUSSION: The loss of endothelial cells followed a biexponential decay and could thus be described by a single equation. The half times of the slow component of the cell loss after surgery were substantially less than for the loss with age, indicating a markedly increased rate of cell loss that persisted for many years after surgery. A mechanism for this accelerated cell loss is suggested that involves a nonspecific, innate response initiated by the breakdown of the blood-ocular barrier. The model was used to calculate endothelial cell loss in the long term after penetrating keratoplasty and to predict when cell density would reach levels that are incompatible with maintenance of transparency and graft function. Thus, a rationale is presented for the setting of minimum donor cell densities by eye banks.

Adolescent↗

PubMed2002

Recovery of endothelial function after vitrification of cornea at -110 degrees C.

PURPOSE: To determine whether endothelial function is retained after ice-free cryopreservation of cornea by vitrification at -110 degrees C. METHODS: Rabbit corneas, mounted on support rings, were exposed to a solution containing 6.8 M propane-1,2-diol (PROH) and cooled at approximately 7 degrees C/min to -110 degrees C, which was below the glass transition temperature (T(g)) of the solution. After rewarming at approximately 12 degrees C/min and removal of the PROH, endothelial function was assessed by monitoring corneal thickness during perfusion at 34 degrees C. RESULTS: Addition and removal of 6.8 M PROH without cooling to -110 degrees C did not markedly impair endothelial function, although corneas were thicker than control samples. There was no visible crystallization of ice during cooling to -110 degrees C; but a few small, discrete sites of crystallization remote from the endothelium, were observed during warming. After removal of the PROH, corneas approximately doubled in thickness during the first 3 hours of perfusion, but they then started to thin, which suggested active control of stromal hydration by the endothelium. This was confirmed in a further set of experiments by removal of bicarbonate ions from the perfusate at this point, which resulted in further swelling at +58 +/- 2 microm/hour (SD; n = 4). Restoring bicarbonate to the perfusate halted this swelling, and the corneas then thinned at -13 +/- 2 microm/hour (n = 4). Morphologically, staining with trypan blue and alizarin red S showed an apparently intact endothelial monolayer. CONCLUSIONS: Rabbit corneal endothelium tolerated exposure to 6.8 M PROH, and endothelial function was evident after vitrification at -110 degrees C. Preliminary morphologic results with vitrified human cornea also showed retention of endothelium.

Aged↗