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Biomedical subjects

John P Whitcher

Publications and source records attributed to John P Whitcher.

18 recordsLinked to original sources

Hookworm infestation as a risk factor for Mooren's ulcer in South India.

OBJECTIVE: To investigate the association between Mooren's ulcer and intestinal hookworm infestation in South India. DESIGN: Prospective observational case-control study. PARTICIPANTS: Fifteen patients with Mooren's ulcer and 30 age- and gender-matched controls seen at Aravind Eye Hospital. METHODS: Stool samples from the Mooren's ulcer patients and controls were collected and analyzed for presence of hookworm infestation. MAIN OUTCOME MEASURE: Prevalence of hookworm infestation in Mooren's ulcer patients and controls. RESULTS: There was a statistically significant correlation between intestinal hookworm infestation and the occurrence of Mooren's ulcer (P = 0.009). Retrospective exploratory subgroup analyses suggested that the correlation between intestinal hookworm infestation and the occurrence of Mooren's ulcer in men (P<0.0001) was stronger than the correlation in women, with no statistically significant difference being observed in the prevalence of hookworm infestation between women with Mooren's ulcer and female control subjects (P>0.99). Similarly, when both the Mooren's ulcer and the control subject groups were analyzed retrospectively by age > 50 years or age < 50, subjects with an age over 50 demonstrated a stronger correlation between hookworm infestation and Mooren's ulcer than controls (P = 0.017), whereas there was no statistically significant difference in the prevalence of hookworm infection between Mooren's ulcer subjects and control subjects < or = 50 (P = 0.31). CONCLUSION: Intestinal hookworm infestation appears to be associated with the development of Mooren's ulcer in South India. Although the power of our retrospective exploratory subgroup analyses was limited by multiple testing and small sample sizes, these data suggest further that the correlation between intestinal hookworm infestation and the development of Mooren's ulcer may be greatest in male patients with more advanced age.

Adolescent↗

Clinical characteristics of Mooren's ulcer in South India.

AIM: To describe the clinical characteristics at presentation of a large cohort of patients with Mooren's ulcer in South India. METHODS: The medical records of patients with Mooren's ulcer examined in the cornea clinic at Aravind Eye Hospital Madurai, Tamil Nadu, India, over a 10-year period were reviewed in this retrospective observational case series. RESULTS: The cohort contained 242 eyes of 166 patients. All patients were from South India, and men outnumbered women by a ratio of 4.7:1. The median and mean ages at presentation were 65 and 61 years, respectively, with a range of 13-95 years. One eye was affected in 90 of 166 (54%) patients. Visual acuity in the affected eye at presentation ranged from 6/6 to light perception, and was 6/12 or better in 34 of 242 (14%) eyes, between 6/12 and 3/60 in 168 (69%) eyes, and worse than 3/60 in 40 (17%) eyes. Partial peripheral corneal ulceration was observed in 222 (92%) eyes, complete peripheral corneal ulceration was observed in 15 (6%) eyes and total corneal ulceration was observed in 5 (2%) eyes. For those 222 eyes with partial peripheral ulceration, 152 (68%) showed temporal involvement, 129 (58%) showed nasal involvement, 116 (52%) showed inferior involvement and 30 (14%) showed superior involvement. Perforation was observed in 26 (11%) eyes, and was more common in eyes with peripheral as compared with total ulceration (p<0.001). Identified risk factors in the cohort included evidence of prior corneal surgery (22%), corneal trauma (17%) and corneal infection (2%). CONCLUSIONS: Mooren's ulcer is a rare and potentially blinding eye condition observed not infrequently in the cornea clinic at Aravind Eye Hospital. Men are affected more often than women and may present with either unilateral or bilateral disease. Perforation is observed in approximately 1 in 10 affected eyes at presentation and occurs most often in the setting of peripheral ulceration. The occurrence of prior corneal surgery, trauma or infection in nearly one third of patients supports theories of exposure to corneal antigen in the pathogenesis of this disorder.

Adolescent↗

Effect of a single mass antibiotic distribution on the prevalence of infectious trachoma.

CONTEXT: The World Health Organization recommends mass antibiotic distributions in its strategy to eliminate blinding trachoma as a public health concern. Some hypothesize that a single distribution is sufficient to control the ocular strains of chlamydia that cause trachoma. Others believe infection will inevitably return and periodic treatments or other measures are essential. OBJECTIVE: To determine whether ocular chlamydial infection returns to the community up to 24 months after a single mass antibiotic distribution in a hyperendemic region of Ethiopia. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study conducted March 2003 to March 2005 in the Gurage Zone of Ethiopia. Eight randomly selected villages were assessed for ocular chlamydial infection. Fifteen untreated villages were randomly chosen at 12 months to allow assessment of a secular trend. INTERVENTION: A single dose of oral azithromycin was offered to all residents of the 8 selected villages who were aged 1 year or older. MAIN OUTCOME MEASURE: Prevalence of ocular chlamydial infection in all children aged 1 to 5 years from each intervention village prior to treatment and 2, 6, 12, 18, and 24 months after mass antibiotic treatment, and also in untreated villages enrolled at 12 months. RESULTS: Five hundred fifteen children were examined for ocular chlamydial infection at baseline. For the follow-up examinations, the mean participation rate was 83%. The mean prevalence of infection in children aged 1 to 5 years decreased from 43.5% (95% confidence interval [CI], 35.0%-52.0%) to 5.1% (95% CI, 1.1%-9.2%) after treatment. On average, infection returned gradually over 24 months to 11.3% (95% CI, 4.5%-18.1%; P = .001). In 7 of 8 villages, infection was higher at 24 months than at 2 months. In the remaining village, no infection could be identified at any point after treatment. Villages enrolled at 12 months had significantly fewer infections than those enrolled 12 months earlier, suggesting a secular trend (P<.001). CONCLUSIONS: Ocular chlamydial infection was not eliminated in children aged 1 to 5 years after a single mass azithromycin distribution; it slowly returned over 24 months, although not to baseline levels. Repeated treatments or other effective measures will be necessary for elimination.

Anti-Bacterial Agents↗

Correlation between clinical suspicion and polymerase chain reaction verification of infectious vitritis.

PURPOSE: To compare polymerase chain reaction (PCR) results to presumptive clinical diagnosis in patients with vitritis. DESIGN: Retrospective review of PCR laboratory records from vitreous samples. METHODS: Fifty consecutive laboratory records of vitreous samples sent for PCR testing were reviewed. Three reviewers with uveitis training ranked the clinical suspicion of a specific diagnosis using a classification system (scale of 1 to 4) and were masked to the PCR results. RESULTS: The degree of clinical suspicion of a particular diagnosis was significantly associated with a positive PCR result (P = .048). Higher clinical suspicion was significantly more associated with a positive PCR result compared with cases with lower clinical suspicion (P = .01). CONCLUSIONS: If the clinical suspicion of a specific diagnosis is low, the PCR for any infectious etiology is unlikely to be positive.

Adult↗

Antioxidants in prevention of cataracts in South India: methodology and baseline data*.

PURPOSE: To describe the methodology and baseline data for the Antioxidants in Prevention of Cataracts (APC) study in South India. METHODS: The APC study is a prospective, 5-year, randomized, triple-masked, placebo-controlled, field-based clinical trial to examine the effect of antioxidants (combination tablet of vitamins A, C, and E) on progression of cataract. The primary outcome variable is cataract progression (nuclear opalescence), evaluated with the slit-lamp biomicroscope by the Lens Opacification Classification System III method. Secondary outcome variables are progression in cortical and posterior subcapsular opacity and nuclear color, change in best corrected visual acuity, myopic shift, and treatment failure (progression to cataract surgery or best corrected vision worse than 20/400 in an eye). Inclusion criteria are age between 35 and 50 years and best-corrected visual acuity of 20/40 or better. Exclusion criteria are a diagnosis of diabetes mellitus or nonfasting blood glucose level>7.8 mmol/L, history or presence of various ocular conditions or treatment forms, or current use of vitamin supplements. Baseline ophthalmic, demographic, and potential cataract risk factor data (such as smoking, sunlight, or alcohol exposure) were compared between groups on an intent-to-treat basis. RESULTS: Of 954 people screened, 798 were enrolled, a sample size which exceeded the required estimate. More than 80% of subjects had 20/20 or better vision in at least one eye, and baseline prevalence of significant cataract according to the LOCS III grading scale was high. The two treatment groups were comparable for all baseline measures except alcohol intake. CONCLUSION: The sample size and group baseline characteristics will provide sufficient power to detect a change in cataract progression within 5 years.

Adult↗

Reliability of transport medium in the laboratory evaluation of corneal ulcers.

PURPOSE: To compare the microbiological yield of corneal ulcer cultures established by direct inoculation of culture media vs indirect inoculation by means of transport medium (Amies without charcoal). DESIGN: Single masked, prospective clinical trial. METHODS: Scrapings were obtained for Gram and potassium hydroxide (KOH) stains from eyes with presumed infectious keratitis and cultured by direct plating onto standard media. Samples were also held in transport media (Amies without charcoal) at room temperature and then plated after 4 and 24 hours. Yields from direct plating vs cultures by means of transport media were compared. RESULTS: Of 100 consecutive eyes examined with presumed infectious keratitis, Gram or KOH stain revealed a bacterial or fungal agent in 69 cases (69%). Of these, 26 were bacterial and 43 fungal. Twenty-two bacterial infections produced positive cultures by direct plating, and all produced the same organism with Amies medium after 4 and 24 hours, respectively. For 43 fungal infections identified by KOH stain, 29 (67%) yielded a positive result after 4 hours in Amies transport medium and 27 (63%) after 24 hours in Amies medium. A total of three cases (7%) that showed fungal infection on KOH stain but did not yield organisms by direct plating did so after inoculation with Amies transport medium. For all comparisons, there was no difference in recovery rates by means of transport medium compared with direct plating (McNemar exact P > .05). CONCLUSIONS: In the clinical setting, Amies transport medium may be a useful alternative to direct inoculation onto blood agar for the laboratory evaluation of infectious keratitis.

Anti-Bacterial Agents↗

Mass antibiotic treatment and community protection in trachoma control programs.

Azithromycin is highly effective against trachoma, but the practical difficulties of community-wide distribution often leave many individuals untreated. We demonstrate, after mass azithromycin treatment of a population in Ethiopia, an indirect protective effect that occurred among untreated children who resided in villages in which most individuals had been treated. Similarities with the indirect protection within a treated community (i.e., "herd protection") that has been observed in vaccination programs are discussed.

Anti-Bacterial Agents↗

Feasibility of eliminating ocular Chlamydia trachomatis with repeat mass antibiotic treatments.

CONTEXT: Mass antibiotic administrations for ocular chlamydial infection play a key role in the World Health Organization's trachoma control program. Mathematical models suggest that it is possible to eliminate trachoma locally with repeat mass treatment, depending on the coverage level of the population, frequency of mass treatments, and rate that infection returns into a community after each mass treatment. Precise estimates of this latter parameter have never been reported. OBJECTIVE: To determine the rate at which chlamydial infection returns to a population after mass treatment and to estimate the treatment frequency required for elimination of ocular chlamydia from a community. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study of 24 randomly selected villages from the Gurage Zone in Ethiopia conducted February 2003 to October 2003. A total of 1332 children aged 1 to 5 years were monitored for prevalence of ocular chlamydial infection pretreatment and 2 and 6 months posttreatment. INTERVENTIONS: All individuals older than 1 year were eligible for single-dose oral azithromycin treatment. Pregnant women were offered tetracycline eye ointment. MAIN OUTCOME MEASURES: Prevalence of ocular chlamydial infection, measured by polymerase chain reaction, in children aged 1 to 5 years, in each of 24 villages at each time point was used to estimate the rate of return of infection and the treatment frequency necessary for elimination. RESULTS: The prevalence of infection was 56.3% pretreatment (95% confidence interval [CI], 47.5%-65.1%), 6.7% 2 months posttreatment (95% CI, 4.2%-9.2%), and 11.0% 6 months posttreatment (95% CI, 7.3%-14.7%). Infection returned after treatment at an exponential rate of 12.3% per month (95% CI, 4.6%-19.9% per month). The minimum treatment frequency necessary for elimination was calculated to be once every 11.6 months (95% CI, 7.2-30.9 months), given a coverage level of 80%. Thus, biannual treatment, already being performed in some areas, was estimated to be more than frequent enough to eventually eliminate infection. CONCLUSION: The rate at which ocular chlamydial infection returns to a community after mass treatment suggests that elimination of infection in a hyperendemic area is feasible with biannual mass antibiotic administrations and attainable coverage levels.

Anti-Bacterial Agents↗

How reliable is the clinical exam in detecting ocular chlamydial infection?

PURPOSE: To describe the relationship between the clinical exam for trachoma and the polymerase chain reaction (PCR) for ocular chlamydia. METHODS: One hundred children in a trachoma-endemic area of Ethiopia were examined three times and swabbed twice for PCR analysis. The assays were compared, and an analysis of the variance between exam and PCR was performed. RESULTS: Inter-examiner agreement was 0.57 (Cohen's kappa), inter-PCR agreement 0.98, and agreement between examiner and PCR, 0.26-0.34. The positive predictive value of the exam in identifying infection was 66%. Inter-examiner variance accounted for 30% of the total variance between the exam and PCR, with the remainder presumably due to an underlying difference in what the exam and PCR measure. CONCLUSIONS: Despite modest inter-grader reliability and correlation with evidence of infection, the clinical exam is widely used due to its convenience and low cost. Efforts to make laboratory tests for ocular Chlamydia trachomatis more affordable would be useful.

Child↗

Trends in the etiology of infectious corneal ulcers at the F. I. Proctor Foundation.

OBJECTIVE: We analyzed laboratory results from corneal ulcers seen from 1976 to 1999 at the Francis I. Proctor Foundation, a referral center in San Francisco, to determine the relative frequencies of pathogens and to analyze for trends in frequencies of the most common pathogens. The results were compared with a previous study of corneal ulcers seen from 1948 to 1976 at the same institution. METHODS: Ulcers presenting to the Proctor Foundation were Gram stained and cultured using standard techniques. Herpetic corneal ulcers were excluded from the study. RESULTS: Organisms were isolated from 427 ulcers, 38% of all cases. Two hundred seventy-eight (59%) isolates were gram-positive bacteria, 145 (31%) gram-negative bacteria, 16 (3%) Acanthamoeba spp., and 36 (8%) fungi. Staphylococcus aureus was the most common organism, composing 20% of all isolates, followed by viridans group streptococci (12%), Streptococcus pneumoniae (11%), Pseudomonas aeruginosa (6%), Moraxella spp. (5%), and Serratia marcescens (4%). Over the 24-year study period the proportion of positive cultures decreased and the incidence of S. marcescens increased significantly. Comparing the period of 1948-1976 to 1976-1999, the frequency of S. pneumoniae and P. aeruginosa decreased, and that of S. marcescens increased significantly. CONCLUSION: The common pathogens associated with corneal ulcers have changed over the past 50 years in Northern California, with S. pneumoniae and P. aeruginosa being isolated relatively less often and S. marcescens being isolated with increasing frequency. The decrease in isolation of organisms over the 1976-1999 period may have resulted from increasing empiric antibiotic treatment by referring ophthalmologists.

Acanthamoeba↗

Pseudogerontoxon.

Pseudogerontoxon is a lesion that resembles a small segment of arcus senilis or gerontoxon and is seen in many individuals with limbal vernal or atopic keratoconjunctivitis. It is an important clinical finding because pseudogerontoxon is often times the only clinical evidence of previous allergic eye disease. To the authors' knowledge, pseudogerontoxon has only rarely been mentioned, and has never been pictured, in the peer-reviewed literature. Three examples are presented of this important clinical entity.

Adult↗

Trachoma decline and widespread use of antimicrobial drugs.

Trachoma is disappearing in many parts of the world, even in the absence of specific control programs. Following mass antimicrobial drug treatments for trachoma in western Nepal, the prevalence of trachoma declined far more rapidly than could be attributed to the control program alone. Pharmacy surveys in the same region found that children received more antichlamydial drugs from sources outside the trachoma program than they did from the program itself. We demonstrate that high background antimicrobial drug use may be responsible for much of the observed decline in trachoma and discuss its potential role in eliminating this infectious disease.

Anti-Bacterial Agents↗

Novel mutations in the CHST6 gene associated with macular corneal dystrophy in southern India.

OBJECTIVE: To further characterize the role of the carbohydrate sulfotransferase (CHST6) gene in macular corneal dystrophy (MCD) through identification of causative mutations in a cohort of affected patients from southern India. METHODS: Genomic DNA was extracted from buccal epithelium of 75 patients (51 families) with MCD, 33 unaffected relatives, and 48 healthy volunteers. The coding region of the CHST6 gene was evaluated by means of polymerase chain reaction amplification and direct sequencing. Subtyping of MCD into types I and II was performed by measuring serum levels of antigenic keratan sulfate. RESULTS: Seventy patients were classified as having type I MCD, and 5 patients as having type II MCD. Analysis of the CHST6 coding region in patients with type I MCD identified 11 homozygous missense mutations (Leu22Arg, His42Tyr, Arg50Cys, Arg50Leu, Ser53Leu, Arg97Pro, Cys102Tyr, Arg127Cys, Arg205Gln, His249Pro, and Glu274Lys), 2 compound heterozygous missense mutations (Arg93His and Ala206Thr), 5 homozygous deletion mutations (delCG707-708, delC890, delA1237, del1748-1770, and delORF), and 2 homozygous replacement mutations (ACCTAC 1273 GGT, and GCG 1304 AT). One patient with type II MCD was heterozygous for the C890 deletion mutation, whereas 4 possessed no CHST6 coding region mutations. CONCLUSION: A variety of previously unreported mutations in the coding region of the CHST6 gene are associated with type I MCD in a cohort of patients in southern India. CLINICAL RELEVANCE: An improved understanding of the genetic basis of MCD allows for earlier, more accurate diagnosis of affected individuals, and may provide the foundation for the development of novel disease treatments.

Corneal Dystrophies, Hereditary↗

Eliminating trachoma in areas with limited disease.

The common wisdom is that a trachoma program cannot eliminate ocular chlamydia from a community, just reduce infection to a level where blindness would be minimal. We describe the success of multiple mass antibiotic treatments, demonstrating that complete elimination of infection may be an attainable goal in an area with modest disease.

Anti-Bacterial Agents↗

Disappearance of trachoma from Western Nepal.

We assessed how much of the observed decline in the prevalence of trachoma in a district of Western Nepal was due to an antibiotic treatment program and how much to an underlying secular trend outside of the program. Although antibiotic treatments clearly have an effect at 6 months, we were unable to show that this effect persisted at 12 months; in fact, long-term gains may be due to a secular trend in the area.

Anti-Bacterial Agents↗