Biomedical subjects

B Munoz

Publications and source records attributed to B Munoz.

At least 37 records · Page 2Linked to original sources

PubMed1996

Potential force of infection of human rabies transmitted by vampire bats in the Amazonian region of Brazil.

Human rabies transmitted by bats has acquired greater epidemiologic relevance in various Latin American countries, just when cases transmitted by dogs have decreased. Concern has been heightened by reports of increased rates of bats biting humans in villages in the Amazonian region of Brazil. The aim of the present work was to estimate the potential force of infection (per capita rate at which susceptible individuals acquire infection) of human rabies transmitted by the common vampire bat if the rabies virus were to be introduced to a colony of bats close to a village with a high rate of human bites. The potential force of infection could be then used to anticipate the size of a rabies outbreak in control programs. We present an estimator of potential incidence, adapted from models for malaria. To obtain some of the parameters for the equation, a cross-sectional survey was conducted in Mina Nova, a village of gold prospectors in the Amazonian region of Brazil with high rates of bates biting humans. Bats were captured near dwellings and sent to The Rabies Diagnostic Laboratory at the Center for Control of Zoonoses (Sao Paulo, Brazil) to be examined. To estimate the force of infection, a hypothetical rabies outbreak among bats was simulated using the actual data obtained in the study area. Of 129 people interviewed, 23.33% had been attacked by a vampire bat during the year prior to the study, with an average of 2.8 bites per attacked person. Males (29.41%) were attacked more often than females (11.36%); also, adults (29.35%) were attacked more often than children (8.33%). None of the 12 bats captured in Mina Nova tested positive for rabies, but the force of infection for a hypothetical outbreak was estimated to be 0.0096 per person per year. This risk represents 0.96 cases per 100 area residents, giving an incidence of 1.54 cases of bat-transmitted human rabies per year in the village of Mina Nova (160 inhabitants). The estimated risk is comparable with what has been observed in similar Brazilian villages.

Adult↗

PubMed1995

Five-year incidence and disappearance of drusen and retinal pigment epithelial abnormalities. Waterman study.

PURPOSE: To obtain 5-year longitudinal data on age-related macular degeneration (AMD) that might be useful for disease prognosis, public health planning, and clinical trial development. PATIENTS AND METHODS: Baseline (1985) and 5-year follow-up (1990) fundus photographs of 483 watermen over 30 years of age who participated in a cohort study conducted on the eastern shore of Maryland were graded independently in a reliable, standardized fashion. Eyes in which AMD appeared or disappeared also were graded in a side-by-side fashion. RESULTS: Development of definite choroidal neovascularization and/or disciform scarring occurred in one of 50 participants over 70 years of age, specifically one of 15 participants over 70 years of age with AMD-3 (defined as large or confluent drusen focal hyperpigmentation of the retinal pigment epithelium [RPE], and/or nongeographic atrophy of the RPE). Appearance of large drusen, focal hyperpigmentation, or AMD-3 was age related, occurring in 5%, 1%, and 7%, respectively, of participants aged 50 to 59 years; 17%, 3%, and 14%, respectively, of participants aged 60 to 69 years; and 17%, 9%, and 26%, respectively, of participants aged 70 years or more. Disappearance of large drusen, hyperpigmentation, or AMD-3 occurred in 16 (34%) of 47 participants, 11 (58%) of 19 participants, and 17 (28%) of 61 participants, respectively, who had each feature photographically present in 1985. Among the 47 eyes identified in which AMD-3 developed by independent gradings, 38 cases of AMD-3 (81%) were confirmed on side-by-side grading. Among the 16 eyes identified as having AMD-3 that disappeared, nine disappearances (56%) were confirmed. Borderline differences in appearance of pigment, drusen size, drusen location, or photographic quality may have accounted for disappearance in seven cases (44%). CONCLUSIONS: Prospective studies on the nonneovascular features of AMD (including large drusen and abnormalities of the RPE) must account for the appearance and disappearance of these features and support the idea that side-by-side gradings can complement independent gradings identifying appearance or disappearance of features of AMD.

Adult↗

PubMed1995

Potent and selective inhibitors of leukotriene A4 hydrolase: effects on purified enzyme and human polymorphonuclear leukocytes.

Leukotriene (LT) A4 hydrolase (EC 3.3.2.6) is a bifunctional zinc metalloenzyme that catalyzes the hydrolysis of the unstable epoxide intermediate LTA4 into the proinflammatory substance LTB4 and also exhibits an amidase/peptidase activity toward synthetic substrates. Based on proposed reaction mechanisms for other zinc hydrolases, we have synthesized inhibitors of LTA4 hydrolase and evaluated their effects on the formation of LTB4 from LTA4 using both purified enzyme and intact polymorphonuclear leukocytes. The two most effective inhibitors, an alpha-keto-beta-amino ester (compound IV) and a thioamine (compound VIII), exhibited IC50 values of 1.9 +/- 0.9 and 0.19 +/- 0.12 microM (mean +/- SD, n = 4), respectively. Compounds IV and VIII were also potent inhibitors of LTB4 biosynthesis in ionophore stimulated polymorphonuclear leukocytes with IC50 < 200 nM. At higher concentrations, the biosynthesis of 5-hydroxy-eicosatetraenoic acid was also inhibited with IC50 approximately 10 microM for both substances. In contrast, leukocyte 15-lipoxygenase and platelet LTC4 synthase activity were not inhibited by these substances at the highest concentrations tested, 50 and 10 microM, respectively. Compounds IV and VIII thus exhibit selectivity among enzyme activities in the arachidonic acid cascade. In conclusion, we describe two compounds that are among the most potent and selective inhibitors of LTA4 hydrolase and LTB4 biosynthesis by intact polymorphonuclear leukocytes, described thus far.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1994

Predicting surgical compliance in a cohort of women with trichiasis.

Trichiasis/Entropion are the severe consequences of chronic trachoma during early life. Blindness and vision loss is preventable with timely lid surgery to correct trichiasis. In a trachoma hyperendemic region of Central Tanzania, a two year follow-up survey was conducted among 205 women with trichiasis to determine the proportion who had had surgery and the barriers to having surgery. Only 18% of the women had undergone surgery by the 2 year follow-up. Those who had surgery tended to report more eye problems at baseline and have more corneal opacities at baseline. Barriers preventing women from going to surgery were costs, problem of children left at home alone, and difficulties in identifying someone to accompany them to the health center. Over 2/3 of those who had surgery reported a significant decrease in pain, improvement of vision, and improved ability to carry out activities of daily life. Ways to improve compliance with recommendations for trichiasis surgery need to be developed.

Adolescent↗

PubMed1994

Alpha-ketoamide Phe-Pro isostere as a new core structure for the inhibition of HIV protease.

Studies on the inhibition of HIV-1 protease utilizing a core isostere with replacement of the scissle bond for an alpha-amino-ketone have resulted in the development of an alpha-keto-amide isosteric replacement of the Phe-Pro scissle amide bond. The simple dipeptide isostere was shown to be a promising new core structure for the development of the enzyme inhibitors. The Ki of this core structure was determined to be 6 microM, compared to 230 microM and > 50 microM for the corresponding phosphinic acid and hydroxyethylamine isosteres.

Amides↗

PubMed1993

Development of selective tight-binding inhibitors of leukotriene A4 hydrolase.

Leukotriene A4 hydrolase is a zinc-containing enzyme which exhibits both epoxide hydrolase and aminopeptidase activities. Since the enzyme product leukotriene B4 is an inflammatory mediator, it is of interest to develop selective inhibitors of leukotriene A4 hydrolase as potential antiinflammatory agents and as mechanistic probes. A systematic study on the enzyme specificity and the inhibition of its amidase activity with more than 30 synthetic inhibitors has led to the development of an alpha-keto-beta-amino ester (26) and a thioamine (27) as tight-binding, competitive type transition-state analog inhibitors of the aminopeptidase activity, with Ki values of 46 and 18 nM, respectively. Both compounds also inhibit the epoxide hydrolase activity, with the IC50 values of 1 microM and 0.1 microM for 26 and 27, respectively.

Amino Acids↗

PubMed1993

Examination methods for glaucoma prevalence surveys.

OBJECTIVE: To perform a pilot evaluation of new examination methods for the detection of glaucoma and other causes of visual impairment in rural East Africa. DESIGN: Testing was performed by local eye nurses after a brief training course. Two novel tests of visual function were used, a scotopic sensitivity test and a visual field test performed on a laptop computer. The optic disc was examined with direct ophthalmoscopy after pupillary dilation and compared with standard photographs on a laminated card. Intraocular pressure was measured with a hand-held, electronic tonometer. SETTING: Rural Tanzania. PARTICIPANTS: One hundred twenty adult villagers. RESULTS: The visual function tests could be performed on more than 90% of subjects, and the results were correlated with the size of the optic disc cup, an objective measure of glaucoma injury. CONCLUSIONS: This survey shows the practicality of instrument-based testing of visual function under field conditions.

Adult↗

PubMed1993

Etiology of corneal opacification in central Tanzania.

The frequency and causes of visually significant corneal opacification in central Tanzania was assessed by a population-based survey. The overall prevalence of bilateral corneal opacification was 1.16% (95% CI 0.31-1.44) and unilateral corneal opacification was 2.07% (95% CI 1.55-2.73). Bilateral corneal opacification was most frequently associated with trachoma, keratoconjunctivitis, vitamin A deficiency and measles. Unilateral corneal opacification had similar causes with the addition of cases caused by trauma. Corneal scarring is a frequent occurrence in this region. The majority of cases of corneal opacification are secondary to potentially preventable or treatable causes.

Adolescent↗

PubMed1993

Measuring progression of lens opacities for longitudinal studies.

A number of classifications schemes for the grading of lens opacities have been developed but none of them have been examined for reliability and validity in prospective or longitudinal studies. The purpose of this study was to develop and test a method for determining progression which was sufficiently sensitive to true change and insensitive to measurement error. The method consists of assessing various sources of measurement error, determining the likely magnitude of the error, and setting boundaries for changes in opacification which incorporate this error. Measurement error was assessed in 203 nuclear lens photographs graded using a decimal system and 136 cortical lens photographs graded in 1/16th area. 95% confidence intervals were calculated of the distribution of differences between photographs and graders and the width of this intervals defined as measurement error. The magnitude of the measurement error was +/- 0.7 units for nuclear opacities and +/- 2/16 for cortical opacities. The utility of this approach was tested in a series of 84 clinic patients followed at irregular intervals for up to 3 years. Only one eye showed "improvement" and progression rates ranged from 1.8 to 5.5% for nuclear opacities and 0 to 7.4% for cortical opacities in this clinic-based series. This approach appears to be useful for discarding noise and enabling the assessment of progression for use in longitudinal studies.

Cataract↗

PubMed1992

Effects of three-month doses of ivermectin on adult Onchocerca volvulus.

Onchocerca volvulus worms in nodules from Guatemalan patients treated with four, eight, or 11 single doses of ivermectin (150 micrograms/kg of body weight) that were given once every three months were examined by routine histologic techniques and compared with worms in control nodules from untreated persons living in the same location over the same time periods. All treated nodules were removed four months after the last dose of ivermectin, i.e., 13, 25, or 34 months after the start of the trial. At the 25th and 34th months, i.e., after the eighth or eleventh doses of ivermectin, there were excess mortalities in female worms of 25.5% and 32.6%, respectively, over and above the levels in controls. Furthermore, the proportions of live females still producing scanty embryos up to the gastrula stage were only 7.7% and 18.2%, and no females were producing microfilariae. Ivermectin given at 3-month intervals also reduced significantly the mean numbers of live male worms in nodules, as well as the proportions of inseminated females. This regimen was effective in preventing embryogenesis to the microfilarial stage while, at the same time, it caused a slow but steady attrition of the adult worms.

Adolescent↗

PubMed1992

The natural history of endemic trachoma: a longitudinal study.

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.

Adolescent↗

PubMed1991

Diagnosis of Chlamydia trachomatis eye infection in Tanzania by polymerase chain reaction/enzyme immunoassay.

Detection of Chlamydia trachomatis eye infection is largely unsatisfactory by standard laboratory methods. A polymerase chain reaction/enzyme immunoassay (PCR-EIA) that had previously been successful for diagnosis of genital C trachomatis infection was compared with direct antibody immunofluorescence (DFA) for detection of the organism in conjunctival scrapes. 234 Tanzanian children aged 1-7 years living in a village that had had no previous trachoma control programme were classified clinically as having no sign of trachoma (0) n = 97, follicular trachoma (TF) n = 100, or intense inflammatory trachoma with or without TF (TI +/- TF) n = 37. PCR-EIA detected C trachomatis in 24%, 54%, and 95% of subjects, respectively, compared with elementary body (EB) detection by DFA of 1%, 28%, and 60%, respectively. Overall prevalence of chlamydial eye infection was 22% by DFA compared with 48% by PCR-EIA. Of subjects with chlamydial DNA at pretreatment, 103 (92%) had no detectable chlamydial DNA at the end of 4 weeks of ocular tetracycline. The findings show that PCR-EIA is likely to affect trachoma diagnosis and epidemiology because of the increased sensitivity for detection of C trachomatis in all clinical groups; the less stringent requirements for specimen collection and transport make this method suitable for field use. Moreover, the semi-quantitative aspect of PCR-EIA may be useful for monitoring a decrease in chlamydial DNA after treatment.

Administration, Topical↗

PubMed1991

The epidemiology of trachoma in central Tanzania.

Trachoma is the leading infectious cause of blindness worldwide and data are needed on the epidemiological characteristics of active and residual disease in hyperendemic areas. This study describes the epidemiological characteristics of trachoma in Central Tanzania. Active, inflammatory disease peaks in pre-school children, with 60% showing signs of trachoma. Evidence of past infection, scarring, trichiasis, and corneal opacity, rose with age. In this population, 8% of those over age 55 had trichiasis/entropion. Females of all ages had more trachoma than males, with a fourfold increased risk of trichiasis observed in females. Women who were taking care of children appeared to have more active disease than non-caretakers. Clear evidence of clustering of trachoma by village, and within village, by neighbourhood was found. Clustering persisted even after accounting for differences in distance to water, local religion, and proportion of children with unclean faces. These findings have important implications for a trachoma control strategy.

Adolescent↗

PubMed1991

Ocular and facial skin exposure to ultraviolet radiation in sunlight: a personal exposure model with application to a worker population.

A model of ocular and facial skin exposure to UVB is presented that combines interview histories of work activities, leisure activities, eyeglass wearing, and hat use with field and laboratory measurements of UV radiant exposure. Site-specific exposure is expressed as the product of personal ambient exposure, defined as the ambient exposure while an individual is exposed to sunlight, and factors that describe the ratio of site-specific to personal ambient exposure. Ocular exposure is further corrected by the UV attenuation of typical eyewear. The model was used to compute cumulative and yearly exposures in a population of 838 watermen who work on the Chesapeake Bay and are highly exposed to sunlight. The model was found to be predictive of conditions known to be caused by excessive sun exposure--skin elastosis, climatic droplet keratopathy, and squamous cell carcinoma--and has been useful in several epidemiological studies.

Eye↗

PubMed1991

Comparison of the effects of a single dose and of four six-monthly doses of ivermectin on adult Onchocerca volvulus.

Adult Onchocerca volvulus worms, extracted from nodules of Guatemalans by collagenase digestion, were examined whole and by histological techniques. One group of persons received a single 150 micrograms/kg dose of ivermectin; two other groups (one with older and one with younger nodules) received four similar doses of ivermectin at 6-month intervals. For each group, there were comparable untreated controls. All nodules were removed six months after the last dose. After a single dose, the only significant difference from the controls was in the decreased proportion of female worms producing live microfilariae. After four doses, there were significant increases in the proportions of moribund/dead female worms and of live uninseminated females, when compared with the corresponding controls. There were also fewer male worms present, but this difference was not significant. Six months after the conclusion of the 4-dose regimen, the proportion of female worms producing live microfilariae was significantly lower than in the groups that had received a single dose.

Animals↗

PubMed1990

Association of nonmelanoma skin cancer and actinic keratosis with cumulative solar ultraviolet exposure in Maryland watermen.

To establish the relationship between ultraviolet-B radiation and squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and actinic keratosis (AK), a cross-sectional prevalence survey was performed in a sample of 808 white, male watermen 30 years of age and older residing in the Eastern Shore of Maryland. A measure of personal cumulative ultraviolet-B exposure was determined for each subject from data collected through interviews and field and laboratory measurements. A personal interview elicited skin type, medication history, and other factors. Clinical diagnoses and histologic confirmation were done for current and previously removed skin tumors. The ratio of subjects with SCC to subjects with BCC was approximately 1:1; however, the ratio of BCC to SCC was 1.25:1 because BCC cases were more prone to multiple lesions. Watermen with SCC or AK but not BCC had higher average annual ultraviolet-B doses than age-matched controls. This was particularly marked in watermen younger than 60 years of age. Logistic regression showed that an older age, childhood freckling, and blue eyes significantly increased the risk of the development of all three types of skin tumor. Ease of sunburning was associated with BCC and AK, but not with SCC. Watermen in the upper quartile of cumulative ultraviolet-B exposure had a 2.5 times higher risk for the development of SCC when compared with the lower 3 quartiles. This suggests that high levels of ultraviolet-B exposure are important in SCC occurrence. The risk of AK developing was 1.5 times higher for those whose cumulative ultraviolet-B exposure exceeded the median. The relationship of BCC to cumulative ultraviolet-B exposure was not clear and this suggests that different etiologic mechanisms operate for SCC and BCC.

Adult↗

PubMed1989

Ultraviolet light exposure and risk of posterior subcapsular cataracts.

Posterior subcapsular (PSC) cataracts are a visually disabling form of cataract and account for 40% of surgical cases. Although PSC opacities may occur following intraocular inflammation, trauma, or use of steroids, the cause is often unknown. A case-control study was undertaken to investigate the role of exposure to ultraviolet light in the B range (UV-B) and other potential risk factors for the development of PSC cataracts. Surgical PSC cataract cases from a large rural ophthalmic practice on the lower eastern shore of Maryland were matched with phakic controls without PSC cataract changes from the same geographic area by age, sex, and referral pattern. All patients with PSC opacities who underwent cataract surgery in a 12-month period were chosen. One hundred sixty-eight cases and 168 controls were interviewed regarding sunlight exposure, drug use, occupational history, history of diabetes, hypertension, and other diseases. Matched-pairs analyses indicated that a history of relatively high exposure to UV-B was associated with increased risk of PSC cataracts. The association of PSC cataracts with steroid use and diabetes was reconfirmed. Subjects with blue eyes and less than high school education were also at increased risk for PSC cataracts. Smoking and hypertension were not found to be PSC cataract risk factors. These data suggest that UV-B exposure may be an important risk factor for PSC cataracts.

Adult↗

PubMed1989

Exposure to sunlight and other risk factors for age-related macular degeneration.

As some ultraviolet (UV) radiation is transmitted by the ocular media, there is a growing concern that there may be a possible relationship between long-term exposure to ultraviolet radiation and increased risk of age-related macular degeneration. To address this question, a survey was conducted of 838 Maryland watermen who had well-characterized ocular UV-A and UV-B exposure. Fundus photographs were taken and graded for presence of exudative disease, geographic atrophy, focal hyperpigmentation of the retinal pigment epithelium, and drusen that were large and/or confluent. None of the subjects in these analyses were aphakic. The results suggested that age-related macular degeneration was not associated with cumulative exposure to either UV-A or UV-B. Age and the presence of nuclear opacity were independently associated with an increased risk of macular degeneration. Thus, we found that in phakic subjects, even with high levels of sunlight exposure, there was no evidence of increased risk of age-related macular degeneration associated with UV-B or UV-A exposure.

Adult↗