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Biomedical subjects

C R Dawson

Publications and source records attributed to C R Dawson.

At least 37 records · Page 2Linked to original sources
PubMed1990

The epidemiology of trachoma predicts more blindness in the future.

Trachoma is considered the world's leading preventable cause of blindness, with hundreds of millions of people affected and approximately 6 to 9 million blinded as a result of the disease. It was once endemic in much of the world. It disappeared from most of Europe and North America, coincident with the improvements in hygienic conditions that accompanied the expanding industrial revolution in the latter part of the 19th century. Common wisdom states that trachoma is disappearing from much of the world today as a result of improvement in the standard of living. Unfortunately, this is not a realistic perception. In some hyperendemic areas neither the standard of living nor hygienic conditions are improving. Deaths due to acute infections have been reduced and the population is both growing and aging. In some parts of the world, because of demographics, it is likely that there are more people being exposed to trachoma as children and more will survive to old age when trachomatous blindness develops. In these countries there will be larger numbers of blind individuals in the future than there are today. This will tax public health and economic systems in the involved communities.

Blindness↗
PubMed1990

Chlamydial infection of subcutaneous conjunctival transplants in guinea pigs.

The development and testing of candidate vaccines for trachoma are constrained because only humans and nonhuman primates are susceptible to conjunctival infection with Chlamydia trachomatis. Guinea pig inclusion conjunctivitis (GPIC), an analogous disease of guinea pigs, provides a useful, less expensive model to study ocular chlamydial infections. GPIC is caused by a Chlamydia psittaci strain whose external constituents are very similar to those of C. trachomatis. To develop a better model for studying GPIC immunity, conjunctival pockets were established under the abdominal skin of guinea pigs by subcutaneous implantation. Up to six implants could be produced in each animal. The success rate of implantation was 79.0% (n = 148). These pockets were then infected with GPIC. The organism was recovered from the autografts indicating local replication, and tests for serum antibody by microimmunofluorescence showed production of GPIC-specific antibody of IgG and IgM classes after infection. There was minimal antibody response after moderate inoculating doses to the implants, and the titers increased more slowly than after eye infection with GPIC; with higher concentration of the inoculum, however, the antibody response increased to the same levels as with the ocular challenge but more slowly. Inoculation of pockets with GPIC also produced acute inflammatory changes in infected autografts (n = 101). Histologic examination of infected grafts showed chlamydial inclusions in epithelial cells and significant infiltration with lymphocytes and polymorphonuclear cells. Subcutaneous autografts may provide a useful model for chronologic studies of chlamydial infection. The delayed immunologic response, however, suggests that these pockets of implanted epithelium do not have full access to the immune system.

Abdomen↗
PubMed1989

Limbal disease in trachoma and other ocular chlamydial infections: risk factors for corneal vascularisation.

Ocular infection with Chlamydia trachomatis, whether of genital or endemic trachoma origin, usually produces diffuse infiltration and swelling of the scleral limbus, grey infiltrates of the corneal limbus, and superficial extension of vessels onto the corneal limbus. In genitally transmitted C. trachomatis infections, subepithelial infiltrates have been reported as well. In classic endemic trachoma, limbal changes also include limbal follicles which resolve, leaving Herbert's peripheral pits, and an extensive vascular pannus. To evaluate the limbal changes in trachoma, follow-up studies were done in 1986-1987 in a group of 213 children originally seen between 1969-1972. Pannus formation occurred at a much earlier age than conjunctival scar formation and was an excellent predictor of later severe conjunctival scarring. The evidence from this study suggests that the mechanisms for corneal pannus formation from the limbus are quite different from those for scarring of the conjunctiva.

Adolescent↗
PubMed1989

Selective spread of herpes simplex virus in the central nervous system after ocular inoculation.

The spread of herpes simplex virus (HSV) was studied in the mouse central nervous system (CNS) after ocular inoculation. Sites of active viral replication in the CNS were identified by autoradiographic localization of neuronal uptake of tritiated thymidine. Labeled neurons were first noted in the CNS at 4 days postinoculation in the Edinger-Westphal nucleus, ipsilateral spinal trigeminal nucleus, pars caudalis, pars interpolaris, and ipsilateral dorsal horn of the rostral cervical spinal cord. By 5 days postinoculation, additional sites of labeling included the seventh nerve nucleus, nucleus locus coeruleus, and the nuclei raphe magnus and raphe pallidus. None of these sites are contiguous to nuclei infected at 4 days, but all are synaptically related to these nuclei. By 7 days postinoculation, no new foci of labeled cells were noted in the brain stem, but labeled neurons were noted in the amygdala, hippocampus, and somatosensory cortex. Neurons in both the amygdala and hippocampus receive axonal projections from the locus coeruleus. On the basis of these findings, we conclude that the spread of HSV in the CNS after intracameral inoculation is not diffuse but is restricted to a small number of noncontiguous foci in the brain stem and cortex which become infected in a sequential fashion. Since these regions are synaptically related, the principal route of the spread of HSV in the CNS after ocular infection appears to be along axons, presumably via axonal transport rather than by local spread.

Animals↗
PubMed1989

Trachoma and blindness in the Nile Delta: current patterns and projections for the future in the rural Egyptian population.

A population based survey of trachoma and blindness was conducted in a rural Nile Delta hamlet. Trachoma remains hyperendemic in this region. Active trachoma was common among preschool children; over half had moderate to severe disease. Of residents 25 years old 90% had substantial conjunctival scarring. Severe conjunctival scarring was commoner among women (84%) than men (58%), and three-quarters of older women had trichiasis/entropion compared with 57% of older men. Males and females had equivalent age specific rates of inflammatory disease. Blindness was associated with old age; 17% of residents aged 50 and over were blind. Estimates of blindness based on this survey and other surveys in Egypt indicate that blindness is still a serious public health problem in rural Egypt. The number of blind persons in Egypt will increase from an estimated 420,000 in 1980 to 868,000 by the year 2020. The current crude blindness rate of 1.8% is expected to increase to 2.3% in the year 2000 and to 3.2% in 2020.

Adolescent↗
PubMed1988

Cataract extraction. Risk factors in a health maintenance organization population under 60 years of age.

Risk factors for cataract extraction in a young (less than 60 years of age) urban health maintenance organization population were evaluated in a case-control study. The subjects (72 case-control pairs) subscribed to the Kaiser Permanente Medical Care Program in the San Francisco Bay area and had cataract extraction between 1976 and 1980. All patients had visual acuity of at least 20/40 OU, documented before development of cataracts. Thirty-six (50%) of the 72 cataract extraction patients had at least one known risk factor for cataract formation, including trauma, intraocular inflammation, diabetes mellitus, syphilis, oral or topical steroid use, or previous eye surgery. Male patients were found to be a mean of 4.3 years younger than female patients, and diabetics were found to be a mean of 3.5 years older than nondiabetics. Variables found to be related to cataract extraction in univariate analysis included diagnosis of diabetes mellitus, a family history of cataracts, pulse rate, white blood cell count, and syphilis.

Adolescent↗
PubMed1988

Nonculture methods for diagnosing chlamydial infection in patients with trachoma: a clue to the pathogenesis of the disease?

We studied five different tests for diagnosing conjunctival Chlamydia trachomatis infection in specimens obtained from 100 children with moderate-to-severe trachoma. The tests were Giemsa stain, isolation in cell culture, direct fluorescein-conjugated monoclonal antibody, enzyme immunoassay, and a DNA probe. The Giemsa stain was least sensitive at 29%. The other tests gave essentially equivalent performances: sensitivity ranged from 73% to 84% and specificity from 93% to 100%. Seven of the 45 positive specimens were only positive in cell culture, whereas 11 of the 45 were negative in culture but positive in at least two nonculture tests. We speculate that these discordant results actually reflect the biologic status of the chlamydial infection. There appears to be a stage in the infection where chlamydial antigens and nucleic acids can be detected in the absence of infectivity. This stage of infection may contribute to the pathogenesis of trachoma by providing a source of sensitizing antigen.

Azure Stains↗
PubMed1987

Peripheral adrenergic stimulation and indomethacin in experimental ocular shedding of HSV.

The application of 6-hydroxydopamine to the cornea by iontophoresis, followed by topical epinephrine, effectively induces herpes simplex virus (HSV) shedding from the external eye of latently infected rabbits. In this study the beta adrenergic blocker, Timolol, reduced virus shedding when applied immediately before the epinephrine, but continued administration resulted in increased viral shedding. While indomethacin, a prostaglandin synthesis inhibitor decreased HSV replication in cell culture, it failed to decrease virus shedding when applied topically to the eye in adrenergically stimulated animals. Timolol may act then by its effect on the peripheral cells of the eye rather than by stimulation of virus production in ganglionic neurons. These same animals were subsequently tested for latent infection of the trigeminal and superior cervical ganglia and corneas 14 months after primary infection. Only 2 of 14 animals had virus in the trigeminal ganglia, a finding which suggests that latent virus may be depleted by repeated reactivations. Virus was recovered from corneas of five rabbits by co-cultivation so it is possible that corneal latency occurs in this rabbit model as it does in humans.

Animals↗
PubMed1987

Identifying HSV infected neurons after ocular inoculation.

ICR mice were inoculated intracamerally with McKrae strain herpes simplex virus (HSV) followed by intraperitoneal injection with 3H-thymidine. Infected mice were sacrificed after 3 or 4 days and the eyes, trigeminal ganglia (TG) and superior cervical ganglia (SCG) were embedded in glycol methacrylate, sectioned, and dipped for autoradiography. Light microscopy revealed silver grain labeling over neurons in the ipsilateral retina, TG and SCG of infected animals. No labeling of neurons was noted in the contralateral TG or SCG. Since the DNA of mature neurons does not replicate, we interpret these labeled neurons to represent cells with active replication of HSV. This technique allows the study of HSV infection of the nervous system with excellent tissue preservation. Furthermore, it may be used to distinguish those neurons with intrinsic viral synthesis from those harboring virus synthesized at a distant site with subsequent intracellular spread.

Animals↗
PubMed1987

Histopathology of herpes simplex virus keratouveitis.

Twenty-four eyes removed for complications of HSV keratitis were studied histopathologically. There were 20 men and 4 women with an average age of 61 years. Severe keratitis was seen in 14, moderate in 7, and mild in 3 eyes. Common features associated with severe keratitis were: acute perforation, granulomatous keratitis with giant cells in the stroma and Descemet's region, stromal inflammatory cells, angle-closure, severe iridocyclitis with diffuse or focal infiltration of lymphocytes and plasma cells, low-grade vitritis, choroiditis, and/or retinal periphlebitis. Specimens with moderate to mild keratitis had a similar distribution of inflammation but a lower incidence of granulomatous keratitis.

Adult↗
PubMed1987

A simple system for the assessment of trachoma and its complications.

A simple grading system for trachoma, based on the presence or absence of five selected "key" signs, has been developed. The method was tested in the field and showed good observer agreement, the most critical point being the identification of severe cases of the disease. It is expected that the system will facilitate the assessment of trachoma and its complications by non-specialist health personnel working at the community level.

Allied Health Personnel↗
PubMed1987

Unusual structure of rat conjunctival epithelium. Light and electron microscopy.

The conjunctiva of the adult Sprague-Dawley rat was studied by light microscopy of 3 micron glycol methacrylate sections of whole eyes with lids and by electron microscopy of conjunctiva from the lower fornix. Rat conjunctiva is unique among species studied. All the superficial epithelial cells are squamous cells rather than polyhedral or columnar cells. Furthermore, the goblet cells are aggregated into clusters rather than distributed randomly throughout the epithelium. These clusters are not found at the lid margin or limbus, but are present in the palpebral and bulbar conjunctivae and achieve maximal size and number near the fornix. The stratified squamous epithelium is typical, composed of a layer of basal cells, an intermediate zone of wing cells, and an upper zone of several layers of squamous cells. Dividing cells are seen only in the basal layer. Occasional mononuclear leukocytes are found in the basal and intermediate layers. The goblet cell clusters are largely composed of columnar cells. Goblet cells predominate, but there are also occasional tuft cells, characterized by thick microvilli at their apices. Basal cells form only an incomplete layer beneath the columnar cells, which in places span the entire epithelium. The conjunctiva of the adult rat has few cells with potential for immunological activity. It does not contain appreciable numbers of plasma cells, and lymphoid follicles are absent.

Animals↗
PubMed1987

A microscopic study of herpes simplex virus retinopathy in mice.

ICR white mice were inoculated with herpes simplex virus (HSV) type I in the anterior chamber of one eye. Animals were killed at intervals of 2, 4, 6, 8, and 10 days and both eyes were obtained for light and electron microscopic study of retinal changes. HSV retinopathy developed in 42 (91%) of 46 inoculated eyes. Fourteen (88%) of sixteen noninoculated eyes examined after the sixth postinoculation day developed HSV retinopathy. The earliest signs of retinopathy in the inoculated eye were peripheral retinal vasculitis and inflammatory cells throughout the nerve fiber layer on day 2. No virus was found in retinal tissue until day 4, at which time disruption of outer retinal layers (outer nuclear layer and layer of rods and cones) was observed in the peripheral retina. The earliest signs of retinopathy in the noninoculated eye were isolated foci of outer retinal disruption in the posterior retina on day 6. The inflammation accompanying early retinal changes of HSV retinopathy were more severe in the inoculated eye. Electron microscopy of both eyes revealed viral particles in the inner nuclear and ganglion cell layers at the time of outer retinal disruption, but viral particles were seen only rarely in the outer retinal layers at this stage. Early disruption of normal retinal architecture may be due to infection and destruction of Muller cells. The retinopathy progressed in both eyes to total destruction of the retina by day 10. Viral infection of the retinal pigment epithelium occurred, but viral particles were seen only rarely in the underlying choroid. This model may be useful for the study of HSV retinopathy in humans.

Animals↗
PubMed1986

An unusual Neisseria isolated from conjunctival cultures in rural Egypt.

Seven isolates of an unusual Neisseria sp. were obtained from eye cultures of children in two rural Egyptian villages. These Neisseria utilized only glucose, they exhibited a positive reaction when tested with antisera to crude antigen from Neisseria meningitidis and N. gonorrhoeae, and they did not react with the fluorescent antibody tests for N. gonorrhoeae or with the monoclonal antibodies used to serotype gonococci. The Egyptian isolates had colony morphology more typical of meningococci than gonococci and showed opaque and transparent colony variants. On SDS-PAGE, the major outer-membrane proteins had different patterns than those noted for comparable proteins of meningococci and gonococci; heat-modifiable outer-membrane proteins were present. Four of the six isolates examined had cryptic plasmids of 2.8 megadaltons, which were slightly larger than the cryptic plasmid of N. gonorrhoeae. These plasmids were homologous to the gonococcal cryptic plasmid, but had different restriction enzyme fragment patterns. The DNA from the Egyptian isolates, like DNA from N. meningitidis but unlike DNA from N. gonorrhoeae, could be cut with the restriction enzyme HaeIII. The frequency of transformation into a temperature-sensitive mutant of N. gonorrhoeae was 0.2 for the Egyptian isolates and 0.1 for N. meningitidis, a frequency that was 5-10-fold lower than that for the N. gonorrhoeae control isolates. Whole-cell DNA from the Egyptian isolates showed 68%-73% homology with N. gonorrhoeae and 57%-63% with N. meningitidis. On the basis of our observations, the Egyptian isolates are distinct from N. meningitidis and may represent a variant of N. gonorrhoeae. We suggest that the isolates be called Neisseria gonorrhoeae ssp. kochii.

Bacterial Proteins↗
PubMed1986

Effect of autonomic mediators in recurrent shedding of herpes simplex in the rabbit eye.

After recovery from primary herpes simplex virus (HSV) infection of the eye in rabbits, recurrent shedding of virus in the external eye can be produced by the local application of 6-hydroxydopamine (6-HD) and epinephrine. Surgical sympathectomy did not prevent shedding of HSV with 6-HD/epinephrine so the source of the virus in the outer eye induced by adrenergic stimulation is not just the superior cervical ganglia (SCG). Chemical sympathectomy with 6-HD prior to HSV infection of the cornea led to decreased viral replication in the SCG during acute infection but did not interfere with uptake of the virus and latent or low grade infection of the ganglion. Shedding of virus in the outer eye induced by 6-HD/epinephrine was reduced by treatment with the beta-adrenergic blocker, timolol. These experiments strongly suggest that recurrent HSV shedding in the eye induced by catecholamines is due in part to effects on the peripheral (i.e. post synaptic) cells. While the peripheral neurons are the source of virus, it is possible that not all HSV detected in the external eye is due to release of preformed virus from nerve endings.

Amphetamines↗
PubMed1985

Incidence of cataract extraction in Pima Indians. Diabetes as a risk factor.

The incidence of visually disabling cataract was estimated by the rate of first cataract extraction in a population of Pima Indians in Arizona. The annual age-specific rates of cataract surgery (first and second eyes) were 3.7 to 5.9 times as high as the estimated US rates. Diabetes was a strong risk factor for first cataract surgery in all age and sex groups except in men aged 75 to 84 years. Overall, with age and sex controlled, the rate of first cataract surgery was 2.2 times as high (95% confidence interval, 1.3 to 3.9) in diabetic as in nondiabetic subjects. Cataract surgery was related to the duration and type of treatment of diabetes. Insulin-treated diabetics had about five times the rate of those with normal glucose tolerance. The rate of cataract surgery was lowest in subjects with normal glucose tolerance, somewhat higher in those with impaired glucose tolerance, and even higher with increasing duration of diabetes.

Adult↗
PubMed1985

New view of the surface projections of Chlamydia trachomatis.

Two kinds of surface specializations of chlamydiae have been described: hemispheric projections and spikelike rods. We undertook the present studies to demonstrate chlamydial ultrastructure in greater detail in conventional thin-sectioned specimens. Chlamydia trachomatis (LGV strain L2/434/Bu), cultured for 40 h in L929 mouse fibroblasts, was fixed in glutaraldehyde-acrolein, p-formaldehyde-glutaraldehyde, or glutaraldehyde-osmium tetroxide mixtures, postfixed in osmium tetroxide, stained in uranyl acetate, dehydrated in ethanols, and embedded in Epon. By the use of fixatives that penetrate and fix rapidly, chlamydial outer and plasma membranes were clearly revealed. Our results indicate that the hemispheric projections are specializations of the plasma membrane of elementary bodies. The spikelike projections are found in intermediate forms, originate beneath depressions of the plasma membrane, and extend through the periplasmic space and outer membrane to end with pointed tips. Improved preservation of chlamydiae provides a new, informative view of their complex structure. Significant interactions between chlamydiae and host cells might be influenced by the surface structures shown in this study.

Cell Membrane↗