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Biomedical subjects

C R Dawson

Publications and source records attributed to C R Dawson.

At least 55 records · Page 3Linked to original sources

Demonstration of the mucous layer of the tear film by electron microscopy.

The mucous layer on the ocular surface maintains the stability, spread, and coherence of the tear film and is essential for normal vision. In spite of its importance, the precise thickness and localization of mucus on the surface of the eye are not known because it is not preserved in conventional electron-microscopic preparations. The authors used two different methods to show mucus on the guinea pig cornea and conjunctiva. First, the authors precipitated mucous glycoproteins by adding a quaternary ammonium compound, either cetylpyridinium chloride or hexadecyltrimethylammonium bromide, to aldehyde fixatives. This procedure stabilized the mucus over the goblet cells and adjacent epithelium, although the mucous layer was not preserved uniformly in other areas. Tannic acid intensely stained mucus precipitated by these methods and showed it to be 0.8 micron thick on the cornea and 1.4 micron thick on the conjunctiva. To confirm these results, the authors also prepared specimens of cornea and conjunctiva by freeze substitution. This technique preserved the mucus in a smooth, uninterrupted layer. The thickness of the mucus was somewhat variable; it measured 1.0 micron over the cornea and varied from 2.0 to 7.0 micron over the conjunctiva because of the greater irregularity of the tissue. The authors' results show that mucus constitutes a considerable part of the precorneal tear film and is thicker than was recognized formerly.

Animals↗

Leprosy in a trachomatous population.

In an Egyptian leprosy hospital, 17% of 133 patients had a visual acuity of less than 3/60. Corneal opacity, phthisis bulbi, and cataract accounted for 85% of blindness. Leprosy and trachoma together produce blinding corneal opacity by exposure, leprous keratitis, and trichiasis and entropion. Inturned lids, a late result of conjunctival scarring due to childhood trachoma, were less frequent in patients with lepromatous leprosy than in patients with tuberculoid leprosy; because conjunctival scarring from trachoma depends on cell-mediated immunity, patients with lepromatous leprosy may not have had severe trachomatous scarring develop due to their lifelong abnormality in cellular immunity. In patients with leprosy, even when complicated by trachoma, simple measures to prevent or restore vision include medical treatment of leprosy, surgical correction of lid deformities, sector iridectomy for constricted pupils or central corneal opacities, and cataract extraction.

Adult↗

An expert consultation system for frontline health workers in primary eye care.

In developing countries, blindness is a major health problem whose control depends on the application of simple measures by frontline workers because, in many of these countries, specialist medical care is not readily available. To assist primary health workers in the management of common and potentially blinding eye disorders, we have developed a prototype computer program for a hand-held computer that incorporates a set of guidelines for diagnosis and treatment. This eye treatment program will help evaluate the potential of such devices for improving health care delivery in developing countries. This approach is now feasible because of recent advances in expert system and portable computer technology.

Blindness↗

Therapy selection in an expert medical consultation system for ocular herpes simplex.

This paper describes a general scheme for selecting therapies which can be used in expert medical consultation systems. The scheme consists of a topological sorting procedure within a general production rule representation. The procedure is used to choose among competing therapies on the basis of precedence rules. This approach provides a natural way in which therapy choices can be automatically explained. The precedence rule has the capability to summarize a great many facts elegantly and to insure that the conclusions reached will be mutually exclusive. Precedence rules are computationally more efficient in both storage and time than an equivalent set of production rules. As the number of competing therapies increases this computational advantage increases. An expert consultation system for diagnosis and therapy planning of ocular herpes simplex has been implemented using this approach and examples of the system's output on actual cases of this disease are given.

Antiviral Agents↗

Surface features of the conjunctiva and cornea.

Guinea pig corneal and conjunctival surfaces were examined by transmission electron microscopy and cytochemistry. Some specimens of cornea and conjunctiva were examined morphologically; others were stained with ruthenium red or tannic acid before examination to enhance the detection of glycoproteins at cell surfaces. The epithelia were covered by microvilli and on the cornea also by microplicae. These surface projections were the shortest (150 nm) over the central cornea, and became progressively longer (approximately 300 nm) over the tarsal and fornical conjunctiva. There was a filamentous cell coat (glycocalyx) on the microvilli and microplicae that was best demonstrated in specimens stained with tannic acid. The glycocalyx extended approximately 300 nm from the tips and lateral surfaces of the microvilli and microplicae. Although there were slight local variations in its thickness, the maximum thickness of the cell coat was uniform over the cornea and conjunctiva. Heavy deposits at the cell surface after ruthenium red staining indicated that the cell coat contained many highly charged polyanions. The density of the ruthenium red stain obscured the fine structure of the filaments in the cell coat. The glycocalyx forms a scaffolding that is believed to bind mucus, with its content of immunoglobulins, by weak chemical interactions to the epithelial surface. Therefore, the microvilli, microplicae, and glycocalyx that were demonstrated in this study provide the structural framework that supports and binds a complex of related factors, including tears, mucus, and immunoglobulins, that have the common function of protecting the eye.

Animals↗

Noninfectious ring-shaped keratitis associated with Pseudomonas aeruginosa.

Ring-shaped keratitis appeared in the left eye of a 37-year-old woman who had worn soft contact lenses for more than five years. The corneal ring began to appear within seven days of a central corneal abrasion. Gram staining of the patient's contact lens cleaning solution showed many gram-negative rods, and microbiologic investigations of the patient's soft contact lens and contact lens case disclosed Pseudomonas aeruginosa. There was no clinical or laboratory evidence of an infectious process. Prompt treatment with polymyxin B-bacitracin ointment and prednisolone acetate 1% eyedrops led to resolution of the opacity and a return to the patient's normal visual acuity. The P. aeruginosa endotoxin may have been transferred through the epithelial break into the superficial corneal stroma, leading to ring formation via endotoxin-initiated, properdin-mediated, antibody-independent complement activation.

Administration, Topical↗

Long-term clinical, microbiological, and immunological observations of a volunteer repeatedly infected with Chlamydia trachomatis.

A blind volunteer was inoculated in one eye with an isolate of Chlamydia trachomatis in 1961 and followed for 20 years. During this time, many observations were made of his clinical responses to the first inoculation and several subsequent inoculations with the same and other strains, chlamydial shedding, and antibody and cell-mediated immune responses. Evidence is presented that partial resistance to chlamydial eye infection developed during repeated infections and that antibodies, cell-mediated immune reactions, and specific antigen in conjunctival cells persisted for many years after the last infection. The antibody response was directed mainly against the original infecting immunotype, regardless of whether the response was restimulated by infection with the same immunotype or with other immunotypes. The lymphocyte stimulation response appeared to be species specific.

Antibody Formation↗

An animal model of trachoma II. The importance of repeated reinfection.

An animal model of chronic cicatrizing trachoma has been produced by repeated ocular inoculation with Chlamydia trachomatis serotype E, a genitally transmitted strain. We have now produced a chronic follicular conjunctivitis on cynomolgus monkeys by repeated inoculation with C. trachomatis serotype A, which has been isolated from an area of endemic trachoma. This disease was similar in all respects to that which followed infection with the serotype E strain. Cynomolgus monkeys inoculated with a single dose of serotype E of C. trachomatis strain developed an acute, self-limited follicular conjunctivitis, which was intense for 4 weeks and then slowly subsided. The organism could be reisolated only during the first 4 weeks after inoculation. On reinoculation at 15 and 30 weeks after the initial infections, these animals demonstrated only a mild and transitory clinical response, and the agent could be recovered for only up to 14 days after inoculation. In contrast, repeated weekly reinoculation with either serotype led to a chronic progressive clinical response in these animals, although after the first 6 weeks the agent was isolated only occasionally. This chronic disease was shown not to be due to hypersensitivity to the egg yolk components in which the organism was grown. These data suggest that the serotype of the chlamydial organism may not be as important in determining the clinical course of disease as is the frequency or persistence of exposure to the chlamydial agent. Although a single inoculum produced an acute follicular conjunctivitis, repeated inoculation is needed to produce the chronic disease characteristic of trachoma in this animal model.

Animals↗

Trachoma therapy with topical tetracycline and oral erythromycin: a comparative trial.

Because topical antibiotic treatment has had a limited effect in previous controlled trials against trachoma, treatment with oral erythromycin was compared with topical tetracycline in 6-8-year-old children in southern Tunisia who had potentially blinding active trachoma. A total of 169 children were divided into two groups that were carefully matched for age, sex, locality, and intensity of disease. Oral erythromycin ethyl succinate in a paediatric dosage form was administered to one group and topical 1% tetracycline ointment to the other group, twice daily, six days a week for three weeks. The two treatments were equivalent in effectiveness and resulted in a substantial decrease in disease intensity and a marked reduction in chlamydial infection detected in conjunctival smears. To maintain blood levels of antibiotics known to be effective in the treatment of chlamydial infections with a dosage schedule possible in a trachoma control programme, one of the long-acting tetracyclines (doxycycline or minocycline) might be considered. Such systemic chemotherapy should be limited to selective treatment of individuals who can be adequately monitored.

Administration, Oral↗

Vitamin A in experimental herpetic keratitis.

Systemic vitamin A palmitate at three dosage levels was evaluated for its effect on experimental herpes simplex virus (HSV) keratitis in corticosteroid-treated rabbits. High-dose vitamin A palmitate reduced the severity of herpetic keratitis, but the low or moderate doses did not, and none of the vitamin A treatments affected virus recovery. Vitamin A treatment, however, produced substantial weight loss in uninfected rabbits and in corticosteroid-treated, HSV-infected rabbits. Steroid treatment alone significantly increased the antibody response to HSV, but this effect was not enhanced by vitamin A. The slight beneficial effect on HSV keratitis could be attributed to the known effect of vitamin A on promoting epithelial healing rather than an enhancement of immunity. For this purpose, local application of vitamin A may be just as effective and much less toxic than administration for systemic effect.

Animals↗

Epidemiology of cataract - a major cause of preventable blindness.

Cataract, or opacity of the lens of the eye, is the most common easily correctable cause of blindness in the world. However, little is known of its prevalence and incidence in different regions, particularly in developing countries, or of the relative importance of the various risk factors. This article describes the available knowledge on the epidemiology of cataract in both developing and industrialized countries, and reviews the methods used to obtain these data. The various predisposing factors, such as diabetes, exposure to radiation, and abnormalities of metabolism, along with the possible mechanisms of cataract formation, are also discussed.

Adult↗

Intermittent trachoma chemotherapy: a controlled trial of topical tetracycline or erythromycin.

In communities with endemic blinding trachoma, mass (or "blanket") treatment with a topically applied tetracycline derivative is a standard control measure. The widely used "intermittent" treatment schedule consists of the twice daily application of antibiotic ointment for five consecutive days once a month for six months. In this study, the efficacy of "intermittent" treatment was evaluated for the treatment of severe and moderate intensity trachoma in children in southern Tunisia. Tetracycline or erythromycin ointments (specific antichlamydial drugs) were compared with 5% boric acid ointment (a simple antiseptic) given by the intermittent schedule during the winter and spring. There was a statistically significant degree of improvement at only one examination, four weeks after the full course of treatment had been completed. When re-examined five months later there were no differences in intensity in the three groups. The limited effect of topical chemotherapy might be attributable to several causes, among which could be inadequate drug levels, inadequate treatment periods, reinfection from non-treated children in the community, and auto-infection from extraocular sites (e.g., respiratory tract) in the same child. The possible value of short-term (two weeks) systemic antimicrobial therapy as an additional strategy to prevent blindness of children with potentially blinding active trachoma is discussed.

Boric Acids↗

Serum and tear antibodies to Chlamydia after reinfection with guinea pig inclusion conjunctivitis agent.

Repeated inoculation of th eyes of guinea pigs with the naturally occurring Chlamydia psittaci agent, guinea pig inclusion conjunctivitis (GPIC), showed that animals gradually become susceptible to reinfection with the passage of time after primary infection. Higher levels of serum IgG antibody had a significant association with resistance to challenge inoculation only with a high dose (250 ELD50) but not with a low dose (25 ELD50) inoculum. With each inoculum, however, some animals with high serum antibody were susceptible. the presence of antibodies in tears did not correlate with resistance to the first low-dose challenge inoculation, but both tear IgG and secretory antibody did have a significant association with resistance on the second rechallenge with a high-dose inoculum. Topical treatment of the eye with immune serum or tears during primary infection reduced the amount of agent in the conjunctiva only during the period of application. Local treatment of the eye with heat-killed vaccine prior to primary infection did not produce detectable antibody or protect animals against challenge inoculation; this local immunization did "prime" the animals, however, so that they had an accelerated antibody response after infection. Although there is abundant evidence that local immunity has an important role in resistance to challenge inoculation with GPIC, serum and tear antibody levels correlate equally well with resistance to repeated ocular challenge inoculation. Effective immunization procedures for this chlamydial infection then would involve stimulation of both local and systemic immune responses.

Animals↗

An animal model for cicatrizing trachoma.

An animal model of cicatrizing trachoma was developed in cynomolgus monkeys. This model is consistent with our hypothesis that repeated ocular inoculation of Chlamydia trachomatis, BOUR strain, mimics the repeated reinfection that occurs naturally in endemic human trachoma. A chronic follicular conjunctivitis developed, and scarring later appeared in the superior tarsal conjunctiva. The organism was reisolated after the infection and was also demonstrated cytologically. Specific antichlamydial antibodies of both the IgM and IgG types appeared in the sera of the monkeys. Histopathologic examination of conjunctiva showed a marked lymphocytic response and the presence of germinal centers; areas of conjunctival scar tissue were also examined. Efforts to produce a similar model in rhesus monkeys were less successful.

Animals↗