Influence of salicylates on the rate of accumulation of deoxyribonucleic acid in gastric washings from the guinea pig.
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Biomedical subjects
Publications and source records attributed to A Garner.
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Oxytalan is a fibrillar protein possessing some of the staining and ultrastructural properties of developing elastic tissue. In a study of human corneae we failed to find fibres of this type in five normal specimens but found them in each of 16 examples of keratoconus and 13 cases of post-traumatic or post-inflammatory scarring. In two cases the microfibrillar nature of the deposits was confirmed by electron microscopy, individual microfibrils measuring 10-12 nm in diameter and having profiles suggestive of a tubular structure. Oxytalan formation was intimately associated with the basal lamina of the covering epithelium with, in areas showing disruption of Bowman's layer and scarring, some extension into the superficial collagenous stroma.
The effects of acetylsalicylate (ASA) on the in vitro secretory and electrical properties of Necturus and Rana temporaria gastric mucosa have been studied. The gastric antrum alkalinized the luminal surface, while in the fundus it is likely that acidificaiton and alkalinization occur simultaneously and that net secretion is due to the dominance of one or other of these processes. The histamine H2 receptor antagonist Metiamide was used to inhibit acid secretion for studies on fundic alkalinization in Rana temporaria. Submucosal application of 3 mM ASA for 30 min markedly reduced alkalinization in the antrum and the frog fundus. Following removal of ASA there was only partial recovery of this secretion. The drug caused slight inhibtion of spontaneous acid secretion in Necturus fundus but not of histamine-stimulated acid secretion in the frog fundus. Following salicylate removal, the rate of acid secretion increased to a higher level than before administration in both tissues. There was a small flux of ASA across the mucosa which was greatest in the acid secreting frog fundus (4.38mumol cm-2 min-1) and least in the antrum (2.19 mumol cm-2 min-1). Esposure of the gastric mucosa to ASA was generally associated with a fall in transmucosal electric potential difference and short-circuit current together with an increase in electrical resistance. It is proposed that the greater sensitivity of alkalinization to ASA is responsible for the apparent increase in the rate of acid secretion which occured.
By cannulating the stroma of rabbit corneae, and introducing extracts of retina and vitreous from newborn kittens subjected to vaso-obliterative doses of oxygen, an attempt was made to test the hypothesis that ischaemic retinal tissue releases a factor with vasoformative properties. It was found that, although retino-vitreal extracts from the test animals elicited a positive response in just over half the experiments, the degree of corneal vascularisation provoked by extracts from intact control animals was only marginally less. Consequently our findings do not permit any definite answer regarding the existence of a specific factor responsible for the proliferation of new vessels on the retinal surface in states associated with retinal hypoxia.
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Involvement of the outer eye in Onchocerca volvulus infection is characterized by an inflammatory process around degenerating microfilariae. Individual microfilariae in the cornea may be associated with localized punctate lesions or, especially when present in large numbers, may provoke a sclerosing keratitis due to invasion by fibrovascular pannus from the limbal conjunctiva. Anterior uveitis develops in some patients and can be either granulomatous, probably as a result of direct microfilarial invasion of the iris and ciliary body, or non-granulomatous, in which case the inflammation is likely to be a response to free microfilarial antigens. Posterior segment involvement takes the form of either inflammatory or atrophic lesions, or both. It is possible that the marked atrophy of the retina and choriocapillaris seen in some cases is largely attributable to preceding choroiditis and that the optic nerve atrophy has a similar pathogenesis.
Serological studies in 22 patients presenting with ocular disease attributable to dosage with the beta-blocking agent practolol revealed a raised incidence of antinuclear antibodies. There was also a marginal increase in the incidence of antibodies to smooth muscle in the more severely affected individuals but the incidence of ther autoantibodies and levels of IgG, IgA, and IgM were within normal limits. Semi-quantitative analysis of tears from 14 of the patients showed absence or near absence in the more severely affected patients of secretory IgA, which is indicative of damage to the lacrimal gland. Other immunological parameters in the tears were normal.
The ocular side-effects of prolonged practolol administration concern the cornea and conjunctiva and are related to deficient tear secretion and the formation of an autoantibody which has an affinity for the intercellular zones of squanmous epithelium. Histopathological study of six cases, including a review of the necropsy findings in two, showed destruction of lacrimal gland tissue, epidermalization of the conjunctival epithelium, with epitheliolysis and stromal ulceration of the cornea leading to perforation in two patients. Immunoperoxidase studies showed fixation of specific antibody in the corneal and conjunctival epithelium but, in the one case in which the tissue could be adequately studied, complement fixation could not be demonstrated. Possibly, therefore, the immune response in patients with practolol-induced ocular damage is secondary to the epithelial disturbance rather than its cause.
The argon laser set at 50 mum, 100-150 mW, o-2 s occluded corneal blood vessels in pigmented Dutch rabbits provided the corneal responsible for inducing vascularization was inactive. After arterial treatment with the argon laser retrograde flow in untreated veins was demonstrated by fluorescein angiography. Therefore all corneal new vessels should be treated, not just arteries. Minimal iris damage complicated the laser therapy, but this was not thought necessarily to contraindicate the use of the argon laser to treat corneal blood vessels in man. The iris damage was associated with outpouring of aqueous from the ciliary processes, and it took up to a week for the blood-aqueous barrier to return to its normal state.
A study of almost 1000 outpatients at a London eye hospital showed the presence of asymptomatic yellowish, spheroidal deposits in the peripheral cornea or conjunctiva, or both, in about 6 per cent, with a preponderance of males and older subjects among those affected. This prevalence is less than is observed in people in countries exposed to higher levels of sunlight. Histological study of the deposits showed some tinctorial similarities with pseudoelastic fibres of pingueculae, with which they were sometimes associated, but also significant differences suggesting that the spheroidal deposits might be a composite of degenerate collagen and a second non-collagenous protein. Until a more precise terminology is feasible we suggest that a purely descriptive name such as spheroidal degeneration or droplet keratopathy should be used to describe this entity.
Biomicroscopical examination of the bulbar conjunctiva and anterior episclera of 1000 randomly selected outpatients showed the presence of multiple discrete lipid globules in 30 per cent. The lipid deposits were asymptomatic. Their prevalence was age-related, while their distribution and composition were consistent with origin from the conjunctival blood vessels.
The injection of living microfilariae of Onchocerca volvulus into the vitreous or immediately beneath the retina of rabbits gave rise to a variable degree of choroiditis. Uveal inflammation was most marked in eyes inoculated directly into the retina and subretinal tissue. The choroiditis was characterised by lymphocytic, plasma cell and eosinophil infiltration and was associated in many instances with degeneration of the overlying retina and pigment epithelium. In the eyes of animals killed more than 40 days after inoculation with microfilariae the leucocytic infiltration was usually mild or even absent, and the predominant finding was circumscribed atrophy and degeneration of the retina. It is concluded that the pathogenesis of the lesions in posterior segment onchocerciasis is basically inflammatory with, possibly, a direct toxic action of the microfilariae on the retina.
Live microfilariae of the Cameroon forest and Sudan-savanna strains of Onchocerca volvulus were inoculated into the vitreous or into the subretinal layers of the eyes of rabbits. The lesions produced are described, and are compared with those seen in control animals, which had received inocula of microfilariae-free saline supernate introduced with a similar degree of operative trauma. Control rabbits showed only minor pigment disturbance in the retina and choroid, near the healed operation scars. Infected animals showed evidence of an inflammatory process in the eye, lasting for up to 4 weeks. Fundus lesions developed following inoculation of microfilariae into the vitreous, but they were more frequent and more severe following subretinal inoculation. The lesions produced were: pallor, vascular narrowing, and flattening of the optic disc; subretinal inflammatory exudate, giving rise to a disturbance of pigment in the retinal pigment epithelium; scattered, small choroidoretinal scars, and larger circumscribed areas of choroidoretinitis, sometimes accompanied by optic atrophy. In many eyes inoculated with microfilariae the wincing reflex was lost, indicating some visual impairment. Many of the lesions were similar to those seen in human patients with onchocerciasis, but they developed much more rapidly. Microfilariae inoculated intravenously, or into the periocular tissues, were not observed to penetrate into the eye-ball.
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Retinal changes in accelerated hypertension were studied in seventeen monkeys with experimental hypertension by means of ophthalmoscopy and colour and flourescence photography during life, and by injection and digest preparations and light and electron microscopy after the animals had been killed. Cotton-wool spots developed in all but three monkeys. The arteries became tortuous and dilated and the light reflex decreased in those animals that became hypertensive. The earliest abnormality was a development of many points of fluorescein leakage on terminal arterioles or small arteries. Such leaking points were always present in relation to cotton-wool spots but were not confined to such areas. Focal narrowing of arteries was not observed but arteriolar occlusion and retrograde filling of the distal segment was present in three animals. Superficial linear haemorrhages were noted in five animals. Light microscopy revealed cotton-wool spots which were identical to those observed in man with a collection of swollen axons containing densely staining pseudonuclei. Study of the arterioles by electron microscopy showed findings ranging from normality to extensive necrosis. Many precapillary arteries were constricted and some were virtually occluded. Degenerative changes were present in smooth muscle cells in the wall of many of the constricted arterioles. Many arteries also showed insudation into their wall of plasma which had seeped into the muscular coat displacing and sometimes entirely replacing the smooth muscle cells. Except for arterioles with advanced necrosis, there was no indication of how plasma insudation occurred. Two arterioles with extensive necrosis showed a break within the endothelial cell cytoplasm through which penetration of plasma proteins had probably occurred. The extravascular tissues showed collections of amorphous material, sone of it with the typical banded configuration of fibrin. The sequence of events proposed to explain these features is as follows: (1) The arterioles constrict as the pressure rises, most likely as a result of vascular autoregulation. This may head to occlusion of the precapillary arterioles and is associated with necrosis of vascular smooth muscle. (2) Dilatation then occurs with insudation of plasma into the unsupported wall through a damaged endothelium. This stage probably corresponds to the autoregulatory break-point and is evidenced clinically by focal leakage of fluorescein. (3) Progressive plasma insudation into the vessel wall with further muscle necrosis results in secondary occlusion and the typical picture of advanced fibrinoid necrosis.
The case is described of a benign medulloepithelioma in a child which originally was apparently confined to the iris.
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