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Biomedical subjects

A Ponce de Leon

Publications and source records attributed to A Ponce de Leon.

17 recordsLinked to original sources

Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli.

BACKGROUND: The microscopic examination of sputum for acid-fast bacilli, is a simple and rapid test that is used to provide a presumptive diagnosis of infectious tuberculosis. While patients with tuberculosis with sputum smears negative for acid-fast bacilli are less infectious than those with positive smears, both theoretical and empirical evidence suggest that they can still transmit Mycobacterium tuberculosis. We aimed to estimate the risk of transmission from smear-negative individuals. METHODS: As part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, patients with tuberculosis with mycobacterial isolates with the same DNA fingerprint were assigned to clusters that were assumed to have involved recent transmission. Secondary cases with tuberculosis, whose mycobacterial isolates had the same DNA, were linked to their presumed source case to estimate transmission from smear-negative patients. Sensitivity analyses were done to assess potential bias due to misclassification of source cases, unidentified source cases, and HIV-1 co-infection. FINDINGS: 1574 patients with culture-positive tuberculosis were reported and DNA fingerprints were available for 1359 (86%) of these patients. Of the 71 clusters of patients infected with strains that had matching fingerprints, 28 (39% [95% CI 28-52]) had a smear-negative putative source. There were 183 secondary cases in these 71 clusters, of whom a minimum of 32 were attributed to infection by smear-negative patients (17% [12-24]). The relative transmission rate of smear-negative compared with smear-positive patients was calculated as 0.22 (95% CI 0.16-0.32). Sensitivity analyses and stratification for HIV-1 status had no impact on these estimates. INTERPRETATION: In San Francisco, the acid-fast-bacilli smear identifies the most infectious patients, but patients with smear-negative culture-positive tuberculosis appear responsible for about 17% of tuberculosis transmission.

AIDS-Related Opportunistic Infections↗

Surrogate markers of disease progression in HIV-infected children in Rio de Janeiro, Brazil.

In order to test the predictive value of immune complex-dissociated p24 antigenaemia (ICD-p24Ag), beta 2 microglobulin (beta 2-M), and neopterin as markers of disease progression, 53 HIV-1 infected children (mean age 68 months) and nine HIV-negative controls (mean age 65 months) were studied prospectively for 9 months. Five were classified in category E (CDC-1994) and seroreverted during the study, 14 in category A, nine in category B, and 25 in category C (CDC-1994). Blood samples were taken at medium intervals of 61 days and tested for ICD-p24Ag, beta 2 microglobulin, and neopterin. The results were correlated with clinical outcome and CD4-lymphocyte counts. All three groups (A, B, C) of symptomatic children had similar positivity in an ICD-p24Ag test (48.1, 58.8, and 51.0 per cent, respectively), and all in group E had negative p24 antigenaemia. beta 2 microglobulin and neopterin tests showed no correlation with clinical stages of HIV-1 infection. There was no significant correlation between these three tests with age-matched CD4 lymphocyte counts (p > 0.05). In contrast, the CD4 lymphocyte count correlated well with disease stages. These data suggest that the markers evaluated in the present study do not correlate well with clinical findings or with CD4 lymphocyte counts. Of all the markers tested, CD4 count was the best to predict prognosis of HIV disease in this cohort.

Biomarkers↗

Short-term associations between outdoor air pollution and visits to accident and emergency departments in London for respiratory complaints.

Many epidemiological studies have shown positive short-term associations between health and current levels of outdoor air pollution. The aim of this study was to investigate the association between air pollution and the number of visits to accident and emergency (A&E) departments in London for respiratory complaints. A&E visits include the less severe cases of acute respiratory disease and are unrestricted by bed availability. Daily counts of visits to 12 London A&E departments for asthma, other respiratory complaints, and both combined for a number of age groups were constructed from manual registers of visits for the period 1992-1994. A Poisson regression allowing for seasonal patterns, meteorological conditions and influenza epidemics was used to assess the associations between the number of visits and six pollutants: nitrogen dioxide, ozone, sulphur dioxide, carbon monoxide, and particles measured as black smoke (BS) and particles with a median aerodynamic diameter of <10 microm (PM10). After making an allowance for the multiplicity of tests, there remained strong associations between visits for all respiratory complaints and increases in SO2: a 2.8% (95% confidence interval (CI) 0.7-4.9) increase in the number of visits for a 18 microg x (-3) increase (10th-90th percentile range) and a 3.0% (95% CI 0.8-5.2) increase for a 31 microg x m(-3) increase in PM10. There were also significant associations between visits for asthma and SO2, NO2 and PM10. No significant associations between O3 and any of the respiratory complaints investigated were found. Because of the strong correlation between pollutants, it was difficult to identify a single pollutant responsible for the associations found in the analyses. This study suggests that the levels of air pollution currently experienced in London are linked to short-term increases in the number of people visiting accident and emergency departments with respiratory complaints.

Adolescent↗

Increase in plasma viral load after oral cholera immunization of HIV-infected subjects.

OBJECTIVE: Constant antigenic stimulation of the large immune cell population contained within gut-associated lymphoid tissue during HIV infection may contribute to patients' total viral load. The aim of this investigation was to evaluate the effect of a mucosal antigenic challenge on HIV replication. DESIGN: Prospective clinical study. METHODS: Twelve HIV-1-infected men (mean age, 42.3 years) from the Casa de Apoio Santo Antonio, Rio de Janeiro, Brazil, were immunized with combined whole cell-toxin B subunit oral cholera vaccine. Blood was collected on days 0, 2, 4, 6, 10 and 15 after immunization and plasma was tested for cholera toxin-specific antibody response (IgG and IgA), beta2-microglobulin, and plasma viral load. CD4 lymphocyte counts were performed within 1 week before immunization. Five HIV-infected non-immunized individuals were studied as controls. RESULTS: There were no adverse effects following immunization and no deterioration in clinical outcome during 3 months of follow-up. A transient increase in viral load that ranged from twofold to 60-fold was observed in all cases and was statistically significant on days 2, 6 and 10 (P = 0.017, P = 0.025, P = 0.021, respectively). There was no correlation with CD4 cell counts. None of the non-immunized subjects demonstrated the pattern of viraemia observed after immunization (P > 0.10 on all days). CONCLUSIONS: Our data indicate that mucosal immunization with oral cholera vaccine induces a transient increase in HIV viraemia, regardless of clinical stage of infection and CD4 cell counts. These findings suggest that mucosal stimulation of HIV-infected patients enhances HIV replication.

Administration, Oral↗

Stability of Mycobacterium tuberculosis DNA genotypes.

To assess genotype stability in Mycobacterium tuberculosis, DNA genotypes were compared in sequential isolates from 49 patients who had sputum cultures separated by at least 90 days that grew M. tuberculosis. By use of IS6110 and the polymorphic GC-rich sequence (PGRS) as markers, it was found that paired isolates from 14 (29%) of 49 patients showed changes in their DNA genotypes between isolates (12 in IS6110 genotypes and 2 in PGRS genotypes). Changed IS6110 genotypes were confined to strains with 8-14 bands and were not related to the bacterial drug susceptibility, the patients' human immunodeficiency virus serostatus, or adherence to therapy. Although this rate of change complicates the interpretation of molecular epidemiologic studies, it can be exploited to gain additional insight into disease transmission. Furthermore, IS6110-related mutations may be a major source of genetic plasticity in M. tuberculosis and provide insights into the organism's evolution and virulence.

Antitubercular Agents↗

Air pollution, pollens, and daily admissions for asthma in London 1987-92.

BACKGROUND: A study was undertaken to investigate the relationship between daily hospital admissions for asthma and air pollution in London in 1987-92 and the possible confounding and modifying effects of airborne pollen. METHODS: For all ages together and the age groups 0-14, 15-64 and 65+ years, Poisson regression was used to estimate the relative risk of daily asthma admissions associated with changes in ozone, sulphur dioxide, nitrogen dioxide and particles (black smoke), controlling for time trends, seasonal factors, calendar effects, influenza epidemics, temperature, humidity, and autocorrelation. Independent effects of individual pollutants and interactions with aeroallergens were explored using two pollutant models and models including pollen counts (grass, oak and birch). RESULTS: In all-year analyses ozone was significantly associated with admissions in the 15-64 age group (10 ppb eight hour ozone, 3.93% increase), nitrogen dioxide in the 0-14 and 65+ age groups (10 ppb 24 hour nitrogen dioxide, 1.25% and 2.96%, respectively), sulphur dioxide in the 0-14 age group (10 micrograms/m3 24 hour sulphur dioxide, 1.64%), and black smoke in the 65% age group (10 micrograms/m3 black smoke, 5.60%). Significant seasonal differences were observed for ozone in the 0-14 and 15-64 age groups, and in the 0-14 age group there were negative associations with ozone in the cool season. In general, cumulative lags of up to three days tended to show stronger and more significant effects than single day lags. In two-pollutant models these associations were most robust for ozone and least for nitrogen dioxide. There was no evidence that the associations with air pollutants were due to confounding by any of the pollens, and little evidence of an interaction between pollens and pollution except for synergism of sulphur dioxide and grass pollen in children (p < 0.01). CONCLUSIONS: Ozone, sulphur dioxide, nitrogen dioxide, and particles were all found to have significant associations with daily hospital admissions for asthma, but there was a lack of consistency across the age groups in the specific pollutant. These associations were not explained by confounding by airborne pollens nor was there convincing evidence that the effects of air pollutants and airborne pollens interact in causing hospital admissions for asthma.

Adolescent↗

Epidemiology of Mycobacterium tuberculosis strains in San Francisco that do not contain IS6110.

IS6110 is commonly used as the basis for molecular epidemiologic and diagnostic studies of Mycobacterium tuberculosis. However, strains that do not contain IS6110 have been reported. If common, such strains would pose a limitation for molecular studies of M. tuberculosis. Analysis of a population-based sample from San Francisco of 1569 specimens submitted for fingerprinting demonstrated that the proportion of strains that lack IS6110 is less than 1%. While this low percentage permits IS6110 fingerprinting in San Francisco, it may be problematic in other settings.

Adult↗

Tuberculosis in Mexican-born persons in San Francisco: reactivation, acquired infection and transmission.

SETTING: San Francisco, California. OBJECTIVE: To determine the relative contributions of infection acquired in San Francisco and reactivation of tuberculous infection acquired elsewhere in Mexican-born persons who developed tuberculosis in San Francisco, and to determine the frequency of transmission leading to secondary cases of tuberculosis in other persons. DESIGN: The study population consisted of all Mexican-born tuberculosis patients reported in San Francisco from 1991 through June 1995. All patients had positive cultures for Mycobacterium tuberculosis and DNA fingerprinting of isolates using IS6110 with more than two bands. Patients were classified as infected in San Francisco or infected elsewhere based on pre-defined criteria that included a second DNA fingerprinting technique (polymorphic guanine-cytosine-rich sequence), chart reviews, and selected patient interviews. RESULTS: Of the 43 Mexican-born patients studied, nine (21%) met the definition of infection acquired in San Francisco and 34 (79%) met the definition of reactivation of infection acquired elsewhere. Only one of the 43 cases resulted in two secondary cases in US-born persons. CONCLUSION: One-fifth of the Mexican-born patients who developed tuberculosis in San Francisco acquired their tuberculous infection in San Francisco; transmission from Mexican-born persons leading to tuberculosis in other persons is uncommon.

Cluster Analysis↗

Air pollution and daily mortality in London: 1987-92.

OBJECTIVE: To investigate whether outdoor air pollution levels in London influence daily mortality. DESIGN: Poisson regression analysis of daily counts of deaths, with adjustment for effects of secular trend, seasonal and other cyclical factors, day of the week, holidays, influenza epidemic, temperature, humidity, and autocorrelation, from April 1987 to March 1992. Pollution variables were particles (black smoke), sulphur dioxide, ozone, and nitrogen dioxide, lagged 0-3 days. SETTING: Greater London. OUTCOME MEASURES: Relative risk of death from all causes (excluding accidents), respiratory disease, and cardiovascular disease. RESULTS: Ozone levels (same day) were associated with a significant increase in all cause, cardiovascular, and respiratory mortality; the effects were greater in the warm seasons (April to September) and were independent of the effects of other pollutants. In the warm season an increase of the eight hour ozone concentration from the 10th to the 90th centile of the seasonal change (7-36 ppb) was associated with an increase of 3.5% (95% confidence interval 1.7 to 5.3), 3.6% (1.04 to 6.1), and 5.4% (0.4 to 10.7) in all cause, cardiovascular, and respiratory mortality respectively. Black smoke concentrations on the previous day were significantly associated with all cause mortality, and this effect was also greater in the warm season and was independent of the effects of other pollutants. For black smoke an increase from the 10th to 90th centile in the warm season (7-19 microg/m3) was associated with an increase of 2.5% (0.9 to 4.1) in all cause mortality. Significant but smaller and less consistent effects were also observed for nitrogen dioxide and sulphur dioxide. CONCLUSION: Daily variations in air pollution within the range currently occurring in London may have an adverse effect on daily mortality.

Air Pollutants↗

Methodological issues in studies of air pollution and daily counts of deaths or hospital admissions.

STUDY OBJECTIVE: To review the issues and methodologies in epidemiologic time series studies of daily counts of mortality and hospital admissions and illustrate some of the methodologies. DESIGN: This is a review paper with an example drawn from hospital admissions of the elderly in Cleveland, Ohio, USA. MAIN RESULTS: The central issue is control for seasonality. Both over and under control are possible, and the use of diagnostics, including plots, is necessary. Weather dependence is probably non-linear, and adequate methods are necessary to adjust for this. In Cleveland, the use of categorical variables for weather and sinusoidal terms for filtering season are illustrated. After control for season, weather, and day of the week effects, hospital admission of persons aged 65 and older in Cleveland for respiratory illness was associated with ozone (RR = 1.09, 95% CI 1.02, 1.16) and particulates (PM10 (RR = 1.12, 95% CI 1.01, 1.24), and marginally associated with sulphur dioxide (SO2) (RR = 1.03, 95% CI = 0.99, 1.06). All of the relative risks are for a 100 micrograms/m3 increase in the pollutant. CONCLUSIONS: Several adequate methods exist to control for weather and seasonality while examining the associations between air pollution and daily counts of mortality and morbidity. In each case, care and judgement are required.

Aged↗

Effects of air pollution on daily hospital admissions for respiratory disease in London between 1987-88 and 1991-92.

STUDY OBJECTIVE: To investigate whether air pollution levels in London have short term effects on hospital admissions for respiratory disease. DESIGN: Poisson regression analysis of daily counts of hospital admissions, adjusting for effects of trend, seasonal and other cyclical factors, day of the week, holidays, influenza epidemic, temperature, humidity, and autocorrelation. Pollution variables were particulates (black smoke: BS), sulphur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2), lagged 0-3 days. SETTING AND PATIENTS: All immediate admissions for respiratory disease (ICD 460-519) to hospitals in London health districts in the five years April 1987 to February 1992 for all ages and the 0-14, 15-64, and 65+ age groups. MAIN RESULTS: O3 (lagged one day) was significantly associated with an increase in daily admissions among all age groups, except the 0-14 group, and this effect was stronger in the "warm" season (April-September). In this season, the relative risks of admission associated with an increase in 8 hour O3 levels of 29 ppb (10th to 90th centile) were 1.0483 (95% CI 1.0246, 1.0726), 1.0294 (0.9930,1.0672), 1.0751 (1.0354,1.1163), and 1.0616 (1.0243,1.1003) for all ages and age groups 0-14, 15-64, and 65+ respectively. Very few significant associations were observed with the other pollutants, though these tended to be positive. Controlling for other pollutants made little difference to the O3 coefficients. There was evidence of a threshold at about 40-60 ppb O3 (maximum hourly or maximum 8 hour). CONCLUSIONS: O3 levels in London have a small but significant effect on hospital admissions for respiratory disease at all ages. The possible role of aerollergen as a confounding factor needs to be examined. Unlike other cities where similar effects have been reported, little or no effect of particulates was observed in London.

Acute Disease↗

Health effects of an air pollution episode in London, December 1991.

BACKGROUND: In December 1991 London experienced a unique air pollution episode during which concentrations of nitrogen dioxide rose to record levels, associated with moderate increases in black smoke. The aim of this study was to investigate whether this episode was associated with adverse health effects and whether any such effects could be attributed to air pollution. METHODS: The numbers of deaths and hospital admissions occurring in Greater London during the week of the episode were compared with those predicted using data from the week before the episode and from equivalent periods from the previous four years. Relative risks (RR) (episode week versus predicted) for adverse health events were estimated using log linear modelling and these were compared with estimates from control areas which had similar cold weather but without increased air pollution. RESULTS: In all age groups mortality was increased for all causes (excluding accidents) (relative risk = 1.10) and cardiovascular diseases (1.14); non-significant increases were observed for all respiratory diseases (1.22), obstructive lung diseases (1.23), and respiratory infections (1.23). In the elderly (65 + years) the relative risk of hospital admission was increased for all respiratory diseases (1.19) and for obstructive lung diseases (1.43), and a non-significant increase was observed for ischaemic heart disease (1.04). In children (0-14 years) there was no increase in admissions for all respiratory diseases and only a small non-significant increase for asthma. When compared with control areas the relative risks became non-significant but remained increased. CONCLUSIONS: The air pollution episode was associated with an increase in mortality and morbidity which was unlikely to be explained by the prevailing weather, a coincidental respiratory epidemic, or psychological factors due to publicity. Air pollution is a plausible explanation but the relative roles of nitrogen dioxide and particulates cannot be distinguished.

Adolescent↗

Streptococcal infections and their sequelae in the upper respiratory tract.

Local sequelae of group A beta-hemolytic streptococci (GABHS) are common and can vary from otitis media, sinusitis, cervical adenitis associated with generalized adenopathy, peritonsillitis and persisting symptoms in spite of therapy, GABHS is one of the pathogens isolated in acute or chronic otitis media and in acute maxillary sinusitis. In cervical adenitis associated with generalized adenopathy GABHS is, along with S. aureus, the most commonly recovered bacteria. In peritonsillitis, GABHS can be recovered alone or in combination with anaerobes in 50% of the cases. These sequelae are usually associated with a slow clinical response to therapy and a high percentage of relapses, reinfections, and chronic infections in the presence of a penicillin-sensitive GABHS. One of the possible causes of these so-called failures is the interference that beta-lactamase producing bacteria can have on the activity of penicillin and similar compounds. When to select a beta-lactamase-resistant antibiotic for the treatment of an apparent penicillin-sensitive infection remains an important area for further research.

Adolescent↗

Microvascular anastomosis for the treatment of seizures in patients with cerebrovascular ischemia: a report of five cases.

The authors report five patients who had either generalized or focal seizures in association with occlusion of the internal carotid artery. Two of them developed a motor deficit after having had several seizures. The other three did not develop a fixed neurological deficit, but their seizures had continued in spite of anticonvulsant treatment. After an extracranial to intracranial (EC-IC) bypass, the seizures either stopped or became less frequent. Based on our experience with these patients and our review of the literature, we think that seizures may be the initial or at least an early manifestation of cerebrovascular insufficiency in some patients. An EC-IC bypass may be of help when angiographic evidence of cerebrovascular occlusive disease is found.

Aged↗

Accommodating error analysis in comparison and clustering of molecular fingerprints.

Molecular epidemiologic studies of infectious diseases rely on pathogen genotype comparisons, which usually yield patterns comprising sets of DNA fragments (DNA fingerprints). We use a highly developed genotyping system, IS6110-based restriction fragment length polymorphism analysis of Mycobacterium tuberculosis, to develop a computational method that automates comparison of large numbers of fingerprints. Because error in fragment length measurements is proportional to fragment length and is positively correlated for fragments within a lane, an align-and-count method that compensates for relative scaling of lanes reliably counts matching fragments between lanes. Results of a two-step method we developed to cluster identical fingerprints agree closely with 5 years of computer-assisted visual matching among 1,335 M. tuberculosis fingerprints. Fully documented and validated methods of automated comparison and clustering will greatly expand the scope of molecular epidemiology.

Algorithms↗