The excimer laser in Australia.
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Biomedical subjects
Publications and source records attributed to H R Taylor.
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The relationship between exposure to sunlight and senile cataract, age-related macular degeneration, pterygium, and climatic droplet keratopathy was examined in 838 watermen who work on the Chesapeake Bay. The presence and severity of lenticular, corneal, and macular changes were assessed by either clinical examination or from stereo macular photographs. From detailed exposure histories, ocular exposure was estimated for three bands of visible radiation-violet (400 to 450 nm), blue (400 to 500 nm), or all visible (400 to 700 nm)-as well as for UV-A (320 to 340 nm) and UV-B (290 to 320 nm). The results with each band of visible radiation were similar. Neither cortical nor nuclear cataract was associated with ocular exposure to blue or all visible radiation, but pterygium and climatic droplet keratopathy were more common with higher exposures. Compared with age-matched controls, patients with advanced age-related macular degeneration (geographic atrophy or disciform scarring) had significantly higher exposure to blue or visible light over the preceding 20 years (odds ratio, 1.36 [1.00 to 1.85]) but were not different in respect to exposure to UV-A or UV-B. These data suggest that high levels of exposure to blue or visible light may cause ocular damage, especially later in life, and may be related to the development of age-related macular degeneration.
The effectiveness of commonly used procedures to correct trachomatous trichiasis of the upper lid was examined in a clinical trial in Oman. Lids were graded as having minor trichiasis (five or fewer lashes), major trichiasis (more than five lashes), and defective lid closure. Randomly allocated surgery specific for lid grade was completed in 384 lids, of which 369 (96%) were followed up once or twice approximately 9 and 21 months after surgery. The definition of operative success included no evidence of trichiasis and complete lid closure. Tarsal rotation was the most effective operation and was successful in 80% of cases of minor trichiasis, compared with success rates of 29% for electrolysis and 18% for cryoablation. Tarsal rotation was successful in 77% of cases of major trichiasis, compared with a 41% success rate for tarsal advance and rotation. Surgery for major trichiasis produced a significant improvement in visual acuity in operated vs nonoperated fellow eyes in a regression model incorporating the between-eyes correlation of visual acuity.
To establish the effect of cataracts on glare and contrast sensitivity, we graded type and amount of lens opacity in 110 subjects who underwent two glare tests (Brightness Acuity Tester and Berkeley glare test) and two contrast sensitivity tests (a sine-wave test and Pelli-Robson chart). Twenty-seven subjects (25%) had clear lenses (mean visual acuity of 20/20) and 83 subjects (75%) had early lens opacities (mean visual acuity of 20/40) in otherwise normal eyes. Multiple regression techniques were used to control for the effects of age and visual acuity. Glare test scores were significantly lower for nearly all patients with lens opacities than for patients with clear lenses and were the lowest for patients with lenses with posterior subcapsular opacity. Contrast sensitivity scores were lower for all patients with lens opacities than for patients with clear lenses at high frequencies only; all lens opacity groups scores similarly with each other. These results indicate reduced visual function among patients with cataracts whose visual acuity is only minimally impaired.
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Nine of 18 chimpanzees inoculated with 250 infective third-stage larvae (L3) each developed patent (i.e., positive for microfilariae) Onchocerca volvulus infection. Four of 6 infected chimpanzees that received 200 micrograms/kg ivermectin at 28 days postinfection (pi) became patent, whereas, when ivermectin was given concurrently with L3 challenge only 1 of 6 infected animals developed patent infection. The antibody response to O. volvulus adult worm-derived antigens (OvAg) showed clear differences between patent and nonpatent chimpanzees. Three months pi, all sera detected several OvAg in the range of M(r) 35-120 k. Sera collected 6 mo pi from later patent animals recognized increasing numbers of OvAg, especially in the lower MW range of M(r) 13 to 33 k. Beginning 10 months pi Onchocerca-antigens of M(r) 21, 24, 26, and 28 k were detected only by patent chimpanzee's sera. The antibody response in nonpatent chimpanzees consistently recognized fewer OvAg, most of which were limited to the higher M(r) range (35-120 k). The reactivity of sera from infected chimpanzees to a low molecular weight fraction (LMW) of total OvAg doubled within 6 months pi, and increased continuously in patent animals from 13 until 30 months pi. Serological reactivity of nonpatent animals to LMW-OvAg remained low. The titers of circulating IgG directed against total OvAg increased in all infected chimpanzees, and continued to rise with patency. In nonpatent chimpanzees the antibody production gradually returned to preinfection values. Total and OvAg-specific IgE increased in patent and nonpatent chimpanzees. Also, during prepatency the granulocyte and antibody-mediated in vitro killing of microfilariae of O. volvulus increased in subsequently patent chimpanzees. The in vitro immobilization of L3 remained low.
Trachoma was considered to have been 'eradicated' from the state of São Paulo, Brazil, until 1982 when a number of new cases of trachoma were reported in preschool children in Bebedouro, a small town in northwestern São Paulo. A household survey was undertaken to assess the prevalence and epidemiological characteristics of trachoma. A total of 2939 people of all ages was examined having been selected from a two-stage probalilistic household sampling frame based on census data. Overall, 7.2% of the population had evidence of one or more signs of trachoma and 2.1% had inflammatory trachoma. Inflammatory trachoma was more common in children aged one to ten years, especially in the peripheral urban and rural areas, and was more common in boys. The presence of chlamydia was confirmed by direct fluorescent antibody cytology. No cases of blindness due to trachoma were seen. A number of socioeconomic and hygiene variables were studied in order to determine the independent risk factors for trachoma in a household. Variables significantly associated with the occurrence of trachoma in the household were the number of children in the house aged one to ten years, the 'per capita' water consumption, the frequency of garbage collections, source of water, and the educational level of the head of household. Clustering of trachoma in different parts of this community was entirely explained by the concentration of households with these characteristics.
Individual behaviour has a very large effect on determining the exposure of the eye to solar radiation. To be able to examine the relationship between ocular exposure to ambient ultraviolet radiation and ocular disease, a model was developed previously that assessed cumulative ocular exposure from individual information on work and leisure activities. In this paper, we present a simplified version of the model that uses data on exposure during the middle of the day (9 a.m. to 3 p.m. solar time) during the northern 'summer' months (April to September). The ocular exposure determined by the simplified model is highly correlated with the full model (r = 0.98) and the simplified model predicts 62% of the total ocular exposure. This model should be useful for future epidemiologic studies of sun exposure and eye disease.
Chlamydia-specific antibody-secreting cells have been identified in conjunctiva and draining cervical lymph nodes by an ELISPOT assay in a cynomolgus monkey model of trachoma. These local sites contained numbers of chlamydia-specific B cells that were higher than those in distant inguinal lymph nodes and peripheral blood. The numbers of chlamydia-specific immunoglobulin G-secreting B cells observed were 5 to 57 per 10(6) cells in conjunctiva and 24 to 996 per 10(6) cells in cervical lymph nodes during conjunctival infection or after challenge of immune monkeys with the chlamydial 57-kDa heat shock protein (hsp60). These studies demonstrate a large chlamydia-specific B-cell component in the conjunctiva during ocular chlamydial infection. These results are similar to our findings for chlamydia-specific T-cell responses.
Trachoma is a common blinding disease of humans caused by ocular infections with Chlamydia trachomatis. The cynomolgus monkey is a valuable primate model for the detection, pathobiology, and treatment of this infection. We have used this model system to compare the relative ability of tissue culture, direct fluorescence cytology, a modified polymerase chain reaction, and RNA blotting to detect C. trachomatis following primary infection and reinfection over 34 weeks. Six cynomolgus monkeys were given a primary ocular chlamydia infection, and 20 weeks later they were reinoculated with the same organism. All animals showed brisk inflammatory responses to the primary infection and milder inflammatory reactions to reinfection. All four diagnostic techniques detected chlamydia at 1 week after primary infection, but both nucleic acid detection methods suggested that organisms were present longer after primary infection than did either tissue culture or direct fluorescence cytology (16 weeks for RNA blotting versus 12 weeks for tissue culture). Following reinoculation at 20 weeks, the period of C. trachomatis detection by tissue culture or direct fluorescence cytology (4 weeks) was much shorter than after primary infection. In contrast, nucleic acid detection was positive for up to 5 weeks longer than tissue culture or direct fluorescence cytology. Both polymerase chain reaction and RNA blotting, which involved no amplification step, indicated the presence of organisms during the culture-negative period. These data suggest that live chlamydiae may remain at a site of infection and produce inflammation beyond the time at which standard microbiological techniques are able to detect them.
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There is substantial indirect evidence which suggests that Chlamydia trachomatis can generate inapparent, persistent infections in human. To confirm this directly, we examined ocular chlamydial infection in both the cynomolgus monkey model of trachoma and in patient samples from a trachoma-endemic area. In monkeys, ocular infection was studied over time using direct immunofluorescence cytology (DFA) and a molecular hybridization screening system which targets chlamydial ribosomal RNA. In eleven animals infected once with B serovar, DFA and probe screening of parallel conjunctival swabs gave congruent results through day 42 post-infection. Thereafter, DFA showed clearing of chlamydia and was negative by day 70, as in previous studies. In contrast, hybridization analysis indicated a continuing presence of chlamydial RNA in all samples from all animals through the end of the experiment at day 84 post-infection. Similarly, analysis of swabs from trachoma patients showed that a number of DFA-negative samples gave clear positive signal for chlamydial RNA. Taken together these data indicate that ocular chlamydial infection persists for longer periods than previously thought, judging solely on the basis of DFA, and they support the idea that inapparent ocular chlamydial infection occurs in vivo.
A longitudinal study of trachoma was conducted among 100 members of nine families living in a hyperendemic area of Tanzania. Family members were examined for trachoma every three months for one year and conjunctival specimens were collected for antigen detection, which was performed either by direct fluorescent antibody cytologic analysis or enzyme immunoassay. The serovar specificity of tear antibodies was determined. Overall, young children tended to form a core of those with persistent, often severe, disease who consistently shed Chlamydia. These children are a potential source of infection in their family. Chlamydia could be identified early in the course of presumed recently acquired infections, but not later in resolving infections. This temporal change may account for the discrepancies between demonstrable organisms and clinical disease seen in cross-sectional studies. Several children were identified who did not develop trachoma despite having Chlamydia identified in conjunctival scrapings. Their ability to resist infection may offer clues for vaccine development. The study of serovar specificity is consistent with the intrafamily transmission of trachoma, but was confounded by the large family size and the potential for separate transmission units to occur within large extended families. These observations give further understanding of the natural history and kinetics of the transmission of trachoma that should be of use in developing and evaluating intervention studies.
The full length cDNA of the immunodominant Ov33 protein of Onchocerca volvulus was expressed in E. coli using various vector constructs. Expression was best with the vectors pGEX2T and pCG808fx, yielding fusion protein Ov33-GST and Ov33-MBP, respectively. Purified fusion protein Ov33-GST and O. volvulus antigen extracts (OvAg) were used to compare antibody responses (IgM and IgG-subclasses) of patients infected with O. volvulus, Brugia malayi, Wuchereria bancrofti, Mansonella perstans/Loa loa and of Sudanese control sera. Sera of all groups contained IgM reacting with Ov33-GST and with OvAg. There was no IgG1 response to Ov33-GST. IgG1 responses to OvAg were only detected in filariasis sera. IgG2 and IgG3 responses were not detectable or marginal in all groups. The IgG4 reaction of onchocerciasis patients to Ov33-GST and to OvAg was high, whereas few other filariasis sera contained IgG4 antibodies to Ov33-GST and to OvAg. A serodiagnostic test for onchocerciasis based on detection of IgG4 to Ov33-GST had a sensitivity of 93.3% and a specificity of 96%. An epitope common to Ov33 and to the homologous proteins of other filarial species was demonstrated with a monoclonal antibody. Purified Ov33-MBP fusion protein was used to follow the development of the antibody response of four chimpanzees experimentally infected with O. volvulus. The data indicates that antibodies to Ov33 are induced by developing worms and later parasite stages.
In areas endemic for onchocerciasis, active community-based treatment with ivermectin is preferred to individual diagnosis and treatment. Ideally, all infected persons should be treated, although initially priorities may have to be set at local or national levels. We suggest that all communities with a prevalence of O. volvulus infection of 20% or more in adult males aged 20 years or over should be treated; and that elsewhere facilities for passive treatment should be provided. In some areas, for logistical reasons, treatment may first have to be started in communities with the highest prevalences (perhaps above 40% or even 60%) and then expanded to all endemic communities. The available data suggest that a rapid assessment method based on the examination for nodules will give a simple, acceptable, non-invasive and reasonably reliable method of identifying the communities that should be treated. If a nodule is detected in at least three men from a sample of 30 men aged 20 years or over, the community can be assumed to have a true prevalence of infection of 20% or more and should be included in community-based treatment.
Onchocerciasis is a parasitic disease with blinding consequences infecting approximately 18 million persons worldwide. In hyperendemic areas, nearly half the population are likely to become blind before they die. Blindness reduces the life expectancy of those affected and has an enormous socioeconomic impact on these communities. Ivermectin, given as a single oral dose of 150 micrograms/kg, can control the manifestations of the disease and can be safely distributed on a mass scale in endemic areas. This drug provides hope for the control of what has been until now an untreatable and devastating disease.
Nine of eighteen chimpanzees inoculated with infective third-stage larvae of Onchocerca volvulus developed patent infection with microfilariae in skin biopsies. In all infected chimpanzees the in vitro cellular reactivity to O. volvulus adult worm-derived Ag (OvAg) increased significantly after exposure to third-stage larvae. However, during prepatency the in vitro cellular responses to OvAg decreased gradually in subsequently mf positive (patent) animals, and returned with patency to values not different to those before infection. In non-patent chimpanzees cellular responses remained significantly higher than before infection. Stimulation of PBMC in vitro with bacterial Ag and mitogen did not show any differences between the experimental groups through 20 months p.i. The addition of exogenous IL-2 did not restore the impaired responses of PBMC to OvAg in patent animals. Exogenous IL-2 elicited an additive increase of the cellular response to OvAg in nonpatent, and a mitogenic effect to OvAg in patent animals. Selective depletion of adherent, suppressor/cytotoxic (CD8+), NK cells (CD16+) and the use of autologous serum had no effect on antigenic and mitogenic cellular responsiveness. OvAg-induced IL-2 production decreased after patency, whereas, IL-1 production was significantly greater in both patent and nonpatent than in control chimpanzees. In summary, these data demonstrate that experimental O. volvulus infection in chimpanzees stimulated a substantial cell-mediated immune response. In patent chimpanzees an OvAg-specific cellular hyporesponsiveness occurred before onset of patency, possibly due to decreased IL-2 production and responsiveness.