Mixed lymphocyte culture responses in rabbits undergoing corneal grafting and topical cyclosporine treatment.

Using a vascularized cornea rabbit model closely resembling human high-risk keratoplasty, corneal allografts were performed on three groups of animals that were paired and tested preoperatively by mixed lymphocyte cultures (MLCs). The three groups were group A, unmodified controls with clear corneas; group B, untreated animals with vascularized corneas; and group C, animals treated with topical cyclosporine (CSA) with vascularized corneas. The MLC results were expressed as stimulation indices (SIs) and divided into low (SI < or = 20) and high (SI > 20) responders and were correlated with final outcome of grafts using survival analysis estimates. In group A, five of 13 (38.5%) grafts rejected, the chance of failure depending on the degree of MLC mismatch between donor and recipient (p = 0.02). All allografts in group B rejected regardless of the degree of mismatch. In group C, seven of 12 (58.3%) grafts rejected, indicating that topical CSA significantly improved survival (p = 0.003) compared with group B. Grafts with mild degrees of MLC mismatch (low responders) survived better (p = 0.0003) than did higher degrees of MLC mismatch (high responders), all of which rejected despite treatment. Our results indicate that both corneal vascularization and the degree of donor-recipient matching play important roles in determining corneal graft survival.

Corticosteroids in corneal graft rejection. Oral versus single pulse therapy.

Forty-eight patients with corneal grafts with severe endothelial rejection were randomly assigned to two treatment groups. One group of 24 patients received prednisolone acetate 1% drops hourly and a single intravenous pulse of 500 mg methylprednisolone. The other group of 24 patients received the same topical therapy plus oral prednisone 60 to 80 mg daily. Nineteen (79.2%) grafts survived in the group that received pulse therapy compared with 15 (62.5%) grafts in the oral group; the difference was not significant (P = 0.17). However, in patients who sought treatment early (less than or equal to 8 days) survival rates were 92.3% and 54.5%, respectively, which indicated a significant advantage for pulse therapy (P less than 0.05). Pulse therapy also appeared beneficial in preventing subsequent rejection episodes. Five (26.3%) of the 19 surviving grafts in the group that received pulse therapy had a further rejection episode compared with 10 (66.7%) of the surviving 15 grafts in the oral group; the difference is significant (P less than 0.025).

The use of a single pulse of intravenous methylprednisolone in the treatment of corneal graft rejection. A preliminary report.

In corneal graft rejection, rapid reversal of the rejection process is necessary to minimise endothelial cell loss. Ten consecutive patients with acute endothelial rejection were treated with a single 500 mg pulse of methylprednisolone intravenously and topical prednisolone 1% drops hourly. The rejection episode was successfully reversed in eight (80%) of the 10 grafts. This preliminary trial indicates that cortico-steroid pulse therapy may be beneficial in the management of severe corneal graft rejection with the advantage of avoiding prolonged oral corticosteroid therapy.

Secondary localized amyloidosis of the cornea associated with tertiary syphilis.

Secondary corneal amyloidosis is a rare finding and only 17 cases have been reported in the literature. A case of unilateral secondary localized corneal amyloidosis is presented in a patient with bilateral interstitial keratitis and other stigmata of tertiary syphilis.

Corneal disease in rural Transkei.

A survey of external eye diseases was undertaken in Transkei; a total of 1,519 people were examined. A high incidence of climatic droplet keratopathy was found in the population, and this was a common cause of blindness in elderly men. Only 7 people had pterygia - all women. Both climatic droplet keratopathy and pterygia are believed to result from actinic damage, therefore the discrepancy noted in the prevalence of these two degenerative disorders was unexpected. Xerophthalmia was observed in 5 children, all of whom had mild forms of vitamin A deficiency eye disease. Although the number of children with overt vitamin A deficiency was small (0.58% of children aged less than 15 years), the importance of this finding lies in the possible pool of children without clinical disease but with low levels of vitamin A and therefore more likely to develop and to succumb to infections of the respiratory and alimentary systems. A further 20 people had corneal changes similar to those found in xerophthalmia; but since associated conjunctival signs were absent it is improbable that these changes were secondary to vitamin A deficiency.

Pathogenesis of pterygium.

This paper reviews the histological and epidemiological characteristics of pterygium which suggest that chronic exposure to ultraviolet radiation plays an important role in the pathogenesis of this disorder. However, there is conflicting evidence indicating that chronic inflammation from other causes can induce the disease. The results of two epidemiological surveys undertaken in Southern Africa show that pterygium is not closely linked to other chronic actinic disorders such as pinguecula and climatic droplet keratopathy. Pterygia differ from these disorders by their vascularity which is probably induced by chronic inflammation. On histological examination, we found that excised pterygia contained a lymphocytic infiltration consisting predominantly of T cells. In the pathogenesis of pterygium we believe that chronic irritation (from whatever cause) produces a chronic inflammatory cell infiltration with resultant inflammatory oedema, attempt at repair and cell induced angiogenesis. These processes, together with actinic damage, are responsible for the fibrovascular reaction so characteristic of a growing pterygium.

An animal model for corneal graft rejection in high-risk keratoplasty.

An animal model for corneal graft rejection is described in which corneal neovascularization is induced prior to keratoplasty. This model closely resembles high-risk human corneal grafting, and relies on rejection being initiated solely by the transplanted corneal tissue. All eleven allografts performed using this model rejected; median time to rejection was 17 days. Two treatment regimens were assessed using this rejection model. Topical cyclosporine produced a significant improvement in graft survival (P = 0.0025). When systemic cyclosporine was administered there was a highly significant improvement in graft survival (P = 0.0001).

Stereoscopic mechanisms: binocular responses of the striate cells of cats to moving light and dark bars.

New knowledge concerning the internal structure and response properties of the receptive fields of striate cells calls for a fresh appraisal of their binocular interactions in the interest of a better understanding of the neural mechanisms underlying binocular depth discrimination. Binocular position-disparity response profiles were recorded from 71 simple and B-cells in response to moving light and dark bars. Predominantly excitatory (PE) cells (N = 48) had disparity response profiles that were spatially closely similar to their respective monocular responses. In addition, the centrally located excitatory subregions were flanked on one or both sides by non-specific inhibitory regions. PE cells with a preferred stimulus orientation within 30 degrees of the vertical (N = 17) showed binocular facilitations with maximal values that were always more than twice (mean 3.3) the sum of the two monocular responses to the same stimuli and generally greater than the facilitations shown by cells with orientations more than 30 degrees from the vertical (N = 29; mean 2.2 times the sum of the respective monocular responses). The strength of the binocular facilitation depended on the stimulus contrast, the facilitation decreasing with increasing contrast. The receptive-field disparity distribution of the 31 PE cells capable of making significant horizontal disparity discriminations has standard deviations of 0.37 degrees and 0.40 degrees, respectively. Predominantly inhibitory cells (PI) (N = 23) showed two basic types of disparity response profile: symmetric (N = 17) and asymmetric (N = 6). Uncertainty regarding the precise location of the binocular fixation point in the anaesthetized and paralysed preparation made it difficult to categorize PI cells adequately.

End-stopped cells and binocular depth discrimination in the striate cortex of cats.

Proposals concerning neural mechanisms for binocular depth discrimination have been criticized on the grounds that only striate cells with a preferred stimulus orientation not too far from the vertical can make significant horizontal disparity discriminations. We investigated this claim by preparing a two-dimensional array of position-disparity response profiles to moving light and dark bars from each of 18 cells in the simple family. From these arrays, it was possible to reconstruct disparity response profiles along any axis across the receptive field, irrespective of the cell's optimal stimulus orientation. This analysis showed that cells with a predominantly excitatory binocular response (N = 10) can make precise horizontal disparity discriminations, independent of their optimal stimulus orientation, provided that they are sufficiently end stopped. End-free cells, on the other hand, are effective for horizontal disparity discriminations only if their preferred orientation are near the vertical. Nearly all striate cells we examined were end-stopped to some degree and nearly half had an end inhibition sufficient to reduce the monocular response from the dominant eye to half its maximal amplitude. Cells having a predominantly inhibitory disparity response profile of the symmetric type (N = 8) have an inhibitory profile along every axis across the receptive field. An outline is given of a neural mechanism for the determination of absolute viewing distance based on the sensitivities of striate cells to vertical retinal-image disparities.

Management of bacterial corneal ulcers.

A prospective microbiological study of 48 patients with corneal ulcers due to bacterial infection was performed. Positive cultures of corneal ulcer samples were obtained in 60% of all patients; about half of these patients had received antimicrobial treatment prior to sampling. A relatively high incidence of Staphylococcus epidermidis was isolated from ulcer patients (27%) compared with normal controls (10%). Gram stains of ulcer samples were positive for organisms in only 27% of all patients and were not considered useful in determining initial therapy in this series. We concluded that treatment should be started with a broad combination of antibiotics while awaiting the culture results.

Simple and B-cells in cat striate cortex. Complementarity of responses to moving light and dark bars.

This report is based on the quantitatively recorded responses of 72 striate cells in the simple (S and SH) and B-cell (B and BH) families to narrow (0.14 degrees) moving light and dark bars. Cells were regarded as hypercomplex (SH and BH) if the end-zone inhibition reduced the response to 50% of its peak value. The contrast of the bars was relatively low and matched to be equal but opposite for the two kinds of bar. Average response histograms to the two kinds of bar were recorded separately and only subsequently combined. The response histogram from a given S- or SH-cell shows separate response peaks to the light and dark bars. The number of peaks varies from two to five in different cells. Cells with two response peaks were encountered most commonly (54%), and rather less common were cells with three (31%), four (7.5%), and five (7.5%) peaks. By defining the sequence of the response peaks according to the direction preferred by a moving light bar, the number of distinct spatial patterns of responses to the moving bars increases from four to eight since the first response in the sequence can be either to a light bar or to a dark bar. Examples of all eight responses have been recorded. For cells in the simple family with two response peaks, as well as for B-cells, the width of the light-bar peak was the same as, or closely similar to, that of the dark-bar peak. For S- and SH-cells with more than two response peaks this was also true for the two principal peaks, namely the largest and the next-largest immediately adjacent peak. In the simple family, the mean widths of the two principal response peaks remained closely similar despite the progressive decrease in their respective widths as the number of peaks in the pattern increased from two to five. The mean width of the two principal response peaks from S- and SH-cells (0.6 degrees) was significantly less than the mean width for B-cells (1.4 degrees). For simple-family cells the spatial overlap between the two principal peaks (mean 14%) was always less than 50% of the overall width of the two peaks, whereas for B-cells the overlap (mean 79%) was always greater than 50%. For cells in both the simple and B-cell families the length of the receptive field as given by a moving light bar is the same as that given by a moving dark bar.(ABSTRACT TRUNCATED AT 400 WORDS)

Properties of end-zone inhibition of hypercomplex cells in cat striate cortex.

The response properties of 96 striate cells in anaesthetized and paralyzed cats were examined by using narrow optimally-oriented light bars moved in the preferred direction at optimal velocity. The bar was lengthened systematically at both ends to plot and analyze bilateral length-response curves. We found a linear relationship between the maximum slope of the inhibitory phase of the curve and the strength of the end-zone inhibition for both cell families: simple and B-cells. This observation indicates that the length of the two end-zones as given by a bilateral length-response curve is approximately constant regardless of the strength of the end-zone inhibition for a change in the strength of the inhibition from 10 to 100%.

Direction selectivity of simple cells in cat striate cortex to moving light bars. II. Relation to moving dark bar responses.

The response properties of 84 simple striate cells in anaesthetized (N2O/O2 supplemented with sodium pentobarbital) and paralyzed cats were examined quantitatively using narrow optimally-oriented light and dark bars moving at optimal velocities. Different cells gave two to five spatially-offset response peaks, the light bar and the dark bar response peaks alternating with one another. With only 5 exceptions, the cells had the same preferred direction for movement of the dark bar as for the light bar. Static-field plots were prepared from 32 of the 84 cells using stationary flashing bars. The receptive fields of different cells had from two to four subregions responding either at light on (ON subregion) or at light off (OFF subregion) although one cell had only a single subregion. In the preferred direction of stimulus movement cells gave either the same number of response peaks to moving bars as there were subregions or one additional response peak. The additional response peak, termed a boundary response, always occurred at the end of the sequence of response peaks and was always completely direction selective. The direction selectivities of the individual response peaks in the responses from 49 of the 84 cells were analyzed. To ensure that each response peak and the corresponding peak in the opposite direction both came from the same subregion, the 49 cells were selected on the basis of having a response in the nonpreferred direction sufficient for analysis and of having a stimulus velocity less than 2.5 degrees/s so as to avoid significant spatial shifts of the peaks due to response latencies. For all but two of the 49 cells, the response peaks in any given profile always showed a progressively greater degree of direction selectivity as the stimulus advanced from one subregion to the next, the first subregion giving the least directionally-selective response peak and the last subregion the most directionally-selective peak. This observation was independent of the direction of stimulus motion and of the particular sequence in which the ON and the OFF subregions were traversed by the stimulus. The response patterns observed experimentally have been correlated with theoretical response patterns based on the responses of lateral geniculate neurons.

Binocular simple cells for local stereopsis: comparison of receptive field organizations for the two eyes.

If a cell is to serve as a depth detector in a local stereopsis mechanism, it could indicate the depth of a specific object feature by responding only when that feature is located at the cell's preferred depth and being silent at other depths, the preferred depth varying from cell to cell over a small range. In order to assign a depth value to a particular object feature, the two receptive fields of the cell should respond to one and the same feature in the visual field. This can be done only if the organizations of the two receptive fields are identical or nearly so. Out of 31 cells in the simple family in the cat striate cortex, 15 were selected as having a monocular response from each eye sufficient to be able to examine their receptive field organizations in quantitative detail. The two receptive fields of each cell were remarkably similar in respect to the number, spatial sequence and position disparities of the response peaks to moving light and dark bars, as well as in respect to the relative ocular dominances, peak separations and direction selectivities of the response peaks to the two kinds of bar.

Conractile responses of guinea-pig ileum to high-frequency electrical field stimulation.

The responses of longitudinal muscle-myenteric plexus strips prepared from guinea-pig ileum to high-frequency electrical field stimulation (10-50 Hz) were investigated. The primary high-frequency responses consisted of a cholinergic component that was less susceptible to inhibition by adenyl compounds than the 0.1 Hz twitch response, and a non-cholinergic component which included a considerable degree of direct muscle stimulation which was not affected by adenosine and adenine nucleotides at concentrations up to 100 micro M. High frequency stimulation in the presence of atropine, at concentrations that effectively blocked the contractions produced by high doses of exogenously applied acetylcholine, elicited delayed complex secondary contractions. These contractions were abolished by tetrodotoxin and were inhibited by morphine and adenyl compounds. The secondary contractions were also elicited in choline-free Krebs buffer following treatment with 100 micro M hemicholinium-3 for 2 h; and they were not enhanced by the addition of 1.5 micro M eserine sulphate. By these criteria, it is concluded that the secondary contractions were mediated by a neurogenic, non-cholinergic mechanism. The nature of the spasmogen, which was not identified, is discussed.

Isolation, characterization and opiate activity of beta-endorphin from the pituitary gland of the ostrich, Struthio camelus.

1. Avian beta-endorphin was purified from adenohypophyseal glands of the ostrich Struthio camelus by a procedure involving acid/acetone extraction, NaCl fractionation, CM-cellulose chromatography, Sephadex G-50 chromatography and paper electrophoresis (pH 6.7). 2. The 31-amino acid peptide behaved as a single substance during polyacrylamide-gel electrophoresis and isoelectric focusing, the isoelectric point being 8.84. 3. Ostrich beta-endorphin exhibited significant opiate activity in the guinea-pig ileum preparation.

The effects of calcium concentration on the inhibition of cholinergic neurotransmission in the myenteric plexus of guinea-pig ileum by adenine nucleotides.

1 Adenosine and the adenine nucleotides AMP, ADP, ATP, cyclic AMP, NAD, NADP and NADH produced a dose-related inhibition of the contractile response of guinea-pig ileum longitudinal muscle-myenteric plexus strips to low frequencies (less than 1 Hz) of electrical field stimulation. 2 These compounds inhibited hexamethonium-sensitive contractions induced by nicotine but did not alter the responses to exogenous acetylcholine, and the acetylcholine output from the myenteric plexus was inhibited by the adenyl compounds. These findings indicate that adenine derivatives act at a presynaptic site on postganglionic cholinergic neurones. 3 The degree of inhibition produced by adenine compounds was inversely related to the calcium concentration of the bath fluid over a range of calcium concentrations (1 to 5 mM) that had no effect on the responses of the muscle to exogenous acetylcholine. 4 The inhibition produced by adenine derivatives was antagonized by theophylline and augmented by dipyridamole. Both of these interactions were sensitive to, and synergistic with, alterations of the concentration of calcium in the bath fluid. 5 The results suggest that adenine compounds inhibit acetylcholine release from the myenteric plexus by diminishing the availability of intracellular calcium ions required for neurotransmitter release.

The effects of dipyridamole on the guinea-pig ileal longitudinal muscle-myenteric plexus preparation.

1 The longitudinal muscle-myenteric plexus strip prepared from guinea-pig ileum has been used to study the actions of dipyridamole and its interactions with adenine derivatives. 2 Dipyridamole augmented the inhibitory effects of adenine derivatives on the twitch response induced by 0.1 Hz field stimulation of the preparation. This synergistic effect was apparent with relatively low concentrations of dipyridamole (10 to 100 nM) and after short pretreatment times (1 to 2 min) that did not inhibit the twitch response on their own. Appropriate studies suggested the dipyridamole-adenosine synergism followed a pattern of facilitative agonist competition. 3 Dipyridamole did not inhibit either uptake of [3H]-adenosine by the preparation or adenosine deaminase activity under the same conditions that it exhibited synergism with adenosine. 4 Higher concentrations of dipyridamole inhibited the twitch response, mainly by decreasing acetylcholine release but partly by a direct action on smooth muscle. The direct action of dipyridamole on muscle was not synergistic with adenosine. 5 Fluorescence microscopy showed preferential binding of dipyridamole to the myenteric plexus.