Biomedical subjects
Publications and source records attributed to E Medina.
The assumption that the antimicrobial resistance gene Nramp1 is a major determinant of resistance of mice to infection with virulent Mycobacterium tuberculosis can now be challenged on the basis of published evidence to the contrary. It is likely that, with tuberculosis, Nramp1-determined defenses are subordinate to other defenses.
Six common inbred strains of mice and their F1 hybrids were examined for resistance to infection with the H37Rv strain of Mycobacterium tuberculosis. According to survival times after inoculation of 10(5) CFU intravenously (i.v.), the mice could be classified as being either highly susceptible (CBA, DBA/2, C3H, 129/SvJ) or highly resistant (BALB/c and C57BL/6). F1 hybrids of susceptible and resistant strains were resistant. Although an examination of a limited number of H-2 congenic strains showed that the H-2k haplotype could confer susceptibility on a resistant strain, it was evident that non-major histocompatibility complex (MHC) genes were much more important. Resistant strains all possessed the susceptibility allele of the anti-microbial resistance gene, Nramp1. Results obtained with selected strains infected with 10(2) CFU of M. tuberculosis by aerosol agreed with the results obtained with mice infected i.v. The size of the bacterial inoculum was important in distinguishing between resistant and susceptible strains, in that a 10(7) inoculum overcame the resistance advantage of one strain over another.
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We have previously shown that fibronectin-binding protein I (SfbI) of Streptococcus pyogenes can act as an adjuvant for mucosal-delivered antigens (Medina, E., Talay, S. R., Chhatwal, G. S. and Guzmán, C. A. 1998. Eur. J. Immunol. 28:1069). To characterize the underlying mechanism of the adjuvancity, we investigated the in vitro stimulating activity of SfbI. The SfbI protein promoted a dose-dependent proliferation of mouse spleen cells. Studies performed using cellular subpopulations showed that proliferation involved B cells and was T cell- and macrophage-independent. SfbI also induced lg production by B cells in a T cell-independent manner. The kinetics of lg isotype accumulation in supernatant fluids and the analysis of Ig-secreting cells suggested that SfbI stimulates B cells expressing different Ig isotypes rather than promoting the isotype switching of single subpopulations. Experiments performed with recombinant proteins encompassing different functional domains of SfbI showed that the fibronectin-binding repeats were responsible for B cell activation. The sera from mice immunized by the intranasal route with SfbI did not react with either double-stranded DNA, cardiolipin or collagen. Interestingly, stimulation with Sfbl also resulted in the up-regulation of MHC class 11 molecules expression by B cells and macrophages. The elucidation of the underlying molecular events to the immunomodulatory effect exerted by SfbI will facilitate the exploitation of the potential of this molecule for the generation of mucosal vaccines.
The introduction of tacrolimus as rescue therapy represents a significant advance in the prevention of late graft failure and second liver transplantation. The authors report the blood level monitoring of tacrolimus as a rescue therapy in 21 children who underwent liver transplantation, and they report the dose-concentration relationship in the presence or absence of hepatitis C virus (HCV) in these patients. This was a retrospective study conducted from May 1993 to January 1997. Indication for the conversion from cyclosporine (CsA) to tacrolimus were acute rejection (62%), chronic rejection (33%), and CsA toxicity (5%). Mean daily dose in the first month was 0.32 mg/kg, whereas at the end of the follow-up period it was 0.14 mg/kg. Tacrolimus mean whole blood concentration levels were between 7.1 ng/ml and 9.4 ng/ml, without significant differences over time. Mean daily doses in HCV+ and HCV- patients were 0.08 and 0.24 mg/kg, respectively (p < 0.01), and mean concentrations were 8.3 and 8.4 ng/ml (NS). HCV+ children required a mean dose three times lower than the dose used in HCV- children to obtain the same tacrolimus trough blood level. Therefore, doses in HCV+ children must be decreased to achieve levels within the therapeutic range.
NUPRO Gold Tooth Whitening System was evaluated for efficacy according to the proposed ADA guidelines for acceptance. Sixty participants with discolored anterior teeth participated in a 14-day, double-blind, clinical trial. The participants were matched for age, gender, and oral health status and were given either a placebo gel without the active agent or the NUPRO Gold active gel, which they wore in a custom-fabricated mouth guard for home use. The shade of each participant's maxillary anterior teeth was evaluated using a value-oriented Vita Lumin Vacuum Shade Guide before the study. The same shade guide was used to determine shade changes. Time of use of the agent and potential side effects, such as tooth and gingival hypersensitivity and tissue irritation, were assessed at all recall examinations and were recorded by participants in daily diaries. The average shade change for the placebo users was less than one shade. The average shade change for the NUPRO Gold users was 6.96 shades. Tooth hypersensitivity varied from none to severe. Tissue irritation was minimal. The results of these evaluations indicate that NUPRO Gold is effective as a tooth-whitening system, when administered properly under the supervision of a dentist, with commonly reported side effects of transient tooth sensitivity and minimal gingival sensitivity. Little or no change in tissue health was noted. This study was supported by Dentsply Preventive Care (York, Pennsylvania).
Magnetic resonance cholangiopancreatography (MRCP) is a new noninvasive technique to examine the biliopancreatic tract that have a high diagnostic accuracy. Thus it becomes an appealing modality that can avoid invasive approaches. The purpose of this study was to evaluate the sensitivity and specificity of MRCP in comparison to endoscopic retrograde cholangiopancreatography (ERCP). We studied 41 patients (24 male, 17 female), median age 64.2 years (range 20 to 86 years), in which MRCP and later ERCP were performed; results of both techniques were compared. In the assessment of biliary tract (n = 39), sensitivity/specificity was 100/94.4% in normal bile ducts (n = 18); 100/100% in choledocholithiasis (n = 13); 100/100% in sphincter of Oddi dysfunction (n = 2), and 100/83.3% in neoplasm (3 ampullary tumors, 2 cholangiocarcinomas). In the evaluation of pancreatic duct (n = 32), sensitivity/specificity was 100/95.8% in normal pancreatic duct (n = 23); 80/100% in chronic pancreatitis (n = 5), and 100/75% in pancreatic carcinoma (n = 3). MRCP has very high sensitivity and specificity in the evaluation of the biliary and pancreatic ducts, and can avoid to perform purely diagnostic ERCP, although further studies are required to better assess the effectiveness of the technique.
BACKGROUND: To validate basal glucemia as a control method for non-insulin dependent diabetes mellitus, and to determine the cut-off point that best characterizes good control. PATIENTS AND METHODS: A transversal, observational study of 256 patients who participated in a diabetes mellitus follow-up program during 1993. In the study, glucemia validity indicators were evaluated after making 2 X 2 tables and ROC (receiver operating characteristic) curves for the different values. Control values of glycated hemoglobin was used as to define a good (< 6.5%) and moderate (< 8%). RESULTS: The values of glucemia considered to be "good" as regards control (from 80 to 110 mg/dl, 4.4-6.05 mmol/dl) have good sensitivity (from 97.3% to 100%) and negative predictive values (from 85.7% to 100%) but extremely bad specificity (from 3.8% to 22.7%) and only moderate positive predictive values (from 59.5% to 64.1%) in reference to values of glycated hemoglobin of 6.5%. The same occurs for 8% as regards sensitivity (from 98.6% to 100%), negative predictive value (from 96.4% to 100%) and specificity from 2.1% to 14.5%). Positive predictive value worsens (from 27.8% to 30.3%). The most effective and most accurate values of glucemia in the ROC curves are 150 mg/dl (8.25 mmol/l) if the control of glycated hemoglobin is good, and 170 mg/dl (9.35 mmol/l) if it is moderate. CONCLUSIONS: The glucemia control figures recommended by consensus produce false positives when they are compared to glycated hemoglobin. In the analysis of effectiveness and ROC curves greater accuracy is obtained with glucemia values that are slightly higher than those recommended.
We investigated the relationship between three prognostic markers, CD4 lymphocyte count, serum beta2-microglobulin (beta2M) levels, and CD8+,CD38+ lymphocyte percent, and the association with the rate of development of AIDS. The markers were measured regularly throughout follow-up in 224 patients. The risk of developing AIDS during follow-up was investigated using Cox proportional hazards models. Time-updated values of the prognostic markers were used, which modelled the risk of AIDS according to the latest measurement of the marker rather than using a single value of the marker at baseline. During a median follow-up period of 13.6 months (range 0.5-31.9 months), 34 cases of AIDS occurred. In a univariate analysis, all three markers predicted the development of AIDS; a 10% increase in the percentage of CD8+ T cells expressing CD38+ resulted in an 88% increase in the risk of AIDS (95% confidence interval: 53-130%; p < 0.0001). After adjustment for the current CD4 count and beta2M, a 10% increase in the CD8+,CD38+ population was associated with a 37% increase in the risk of AIDS (95% confidence interval: 4-81%; p = 0.02). Thus, the percentage CD8+,CD38+ level predicts the development of AIDS independently of the latest CD4 count and beta2M. This assay is therefore potentially useful in conjunction with blood CD4 counts and serum beta2M levels in patient management and clinical trial design.
Collagenous colitis (CC) is a cause of chronic aqueous diarrhea with normal radiologic study and endoscopic appearance of the colonic mucosa. Histologically, it is defined by the presence of a thickened subepithelial collagenous band and inflammatory changes of the mucosa. The cause of CC is currently unknown, although several mechanisms have been proposed, such as an inflammatory, autoimmune, origin, disregulation in collagen synthesis, plasma vasculosis and a possible role of bacterial or drug toxins. The clinicopathological data of 12 patients (9 females and 3 males) with a mean age of 52.4 years diagnosed by histologic criteria are presented. Aqueous diarrhea was observed in all the patients with a mean number of 5.4 stools/day during a time period between 3 weeks and 10 years (mean, 14.7 months). In a 6 patients allergies and/or associated diseases, mainly rheumatologic diseases were found. Laboratory and endoscopic data were normal or unspecific, with colon biopsy being carried out in all the patients. Several treatments were tested with good response with sulphasalazine derivatives, corticoids, antibiotics, and mebeverine, with no solution to the diarrhea in 2 patients. A review of the literature is also provided.
BACKGROUND: Health population inquiries give information about morbidity as perceived by people, the quality of medical care and the costs of diseases. AIM: To inform the results on morbidity and medical care surveys performed in the Chilean cities of Antofagasta, La Serena, Concepción, Temuco, Llay Llay, Tiltil y Lampa-Batuco. MATERIAL AND METHODS: A random sample of 951 dwellings with 4.192 people was selected and studied three times, in 1995 and 1996. All health events (acute and chronic disease episodes, accidents, health examinations, dental care) and the main features of medical care were registered in the interviews which covered a 2-week period each time. RESULTS: Health events were registered in 30.1% people. When extrapolating fortnight findings to a one year period, each person had 2.37 annual episodes of acute diseases, 0.94 health examinations and 0.69 dental attentions. The prevalence of chronic diseases was 13.2%. The frequency of health events was higher among women and in elders. Hospital stays and deaths were less frequent in higher income levels. Most acute diseases were respiratory illnesses, followed by communicable diseases. The most important chronic diseases detected were hypertension, diabetes mellitus, bronchial asthma and heart diseases. Medical care was provided in 66% of acute and 34% of chronic diseases. CONCLUSIONS: When comparing these results with previous surveys, an increase in the frequency of acute and chronic diseases is found.
BACKGROUND: In countries with an intermediate development level such as Chile, health care is the main factor that improves the health status of the community. AIM: To inform the results of morbidity and medical care surveys performed in the Chilean cities of Antofagasta, La Serena, Concepción, Temuco, Llay Llay, Tiltil y Lampa-Batuco. MATERIAL AND METHODS: A random sample of 951 dwellings with 4,192 people was selected and studied three times, in 1995 and 1996. All health events (acute and chronic disease episodes, accidents, health examinations, dental care) and the main features of medical care were registered in the interviews which covered a 2-week period each time. RESULTS: Half of sick people received medical care and the rest was managed with self care techniques. Sixty nine percent of subjects with acute diseases received medical care, compared to 32% of those with chronic diseases. The National Health Fund (FONASA) financed most of these medical attentions, half of these were done in private centers and the rest in public premises. Private centers took care of 71% of acute patients, 48% of chronic patients and 27% of health controls. The proportion of private care in different cities paralleled the income of their populations. An estimation of 3.5 medical attentions per capita per year in these cities can be reached. Health care was considered very good by 33% of patients, as good by 55%, as regular by 9% and as deficient by 3%. Quality of care of private centers was perceived as better than that of public centers. Eighty five percent of sick people that did not seek medical care, did so due to the mildness of their ailments. People had to afford a mean of US$ 30 per episode of acute disease, US$ 32 per episode of chronic disease and US$ 56 per each dental attention. CONCLUSIONS: Two thirds of patients with acute diseases and one third of patients with chronic diseases received medical care during the study period.
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The superior resistance of some strains of mice over others to infection with certain intracellular pathogens, including the vaccine strain of Mycobacterium bovis, bacillus Calmette Guerin (BCG), is determined by a gene associated with a small segment of chromosome 1 designated by Ity/Lsh/Bcg locus, referred to here as the Bcg locus. DBA/2 mice containing the dominant resistant allele of the Bcg gene (Bcgr), major histocompatibility complex-compatible BALB/c mice containing the recessive susceptible allele (Bcgs), and congenic C.D2-N20 Bcgr, which are genetically the same as BALB/c mice except for possessing a small piece of DBA/2 chromosome 1 containing the Bcg locus, were used to determine whether the Bcg gene determines resistance to infection with the virulent H37Rv strain of Mycobacterium tuberculosis (Mtb). According to the survival times of Bcgr and Bcgs mice infected via either the intravenous or respiratory route, Bcgr mice proved much less, rather than more, resistant to Mtb infection than Bcgs mice. Shorter survival times of Bcgr mice were associated with an inferior capacity to control Mtb growth in their lungs and to retard the development of Mtb-induced pathology in this organ. Resistance to Mtb infection was a dominant trait in the F1 progeny of Bcgr and Bcgs mice. The results show that resistance to Mtb is not determined by the resistance allele of the Bcg gene nor by the recently isolated candidate Bcg gene Nramp1, located in the Bcg locus.
In mice, natural resistance to infection with BCG is under the influence of an autosomal gene designated Bcg. It is shown here in agreement with others that mice that possess the dominant resistant allele of the gene (Bcgr) are more capable than mice that possess the susceptible recessive allele (Bcgs) at restricting the growth of BCG in their lungs, as well as in their spleens, during the first 20 days of infection. It is shown, in addition, that in the absence of specific immunity the resistance difference between Bcgr and Bcgs mice became much more pronounced as infection progressed beyond day 20. Whereas T cell-depleted Bcgr mice developed a capacity after day 20 to cause infection in their lungs and spleens to stabilize and plateau for at least 40 days, T cell-depleted Bcgs mice were unable to prevent infection from progressing in these organs. On the other hand, both types of T cell-depleted mice were capable of causing infection to plateau in their livers and kidneys. Moreover, this T cell-independent mechanism of resistance was essentially abolished in all organs in which it was expressed by treating the mice with hydrocortisone. In the lungs of immunocompetent Bcgs mice, failure to stabilize infection was associated with heavily infected macrophages and failure to contain BCG at original sites of infection.
Nramp1 is a recently cloned gene that is involved in resistance of mice to infection with certain microbial pathogens, including the attenuated bacillus Calmette-Guérin (BCG) strain of Mycobacterium bovis, as well as certain other mycobacteria. With a view to determining whether Nramp1 influences resistance of mice to infection with virulent M. tuberculosis, BALB/c mice homozygous for the susceptibility allele of Nramp1, and DBA/2 mice homozygous for the resistance allele, as well as their F1 and F2 progeny, were typed according to their possession of these alleles using a 'hot start' polymerase chain reaction (PCR) procedure. As assessed by the ability of the mice to survive infection, the results show that Nramp1 plays no discernible role in resistance to tuberculosis.
OBJECTIVE: To look for surrogate markers in HIV-1 infection that can predict the decline of CD4+ T cells. METHODS: Multiparameter flow cytometric analyses of CD8+ lymphocytes were performed. These cells were investigated for their expression of the activation marker CD38+ within the naive (CD45RA+) and primed (CD45RO+) subsets. Serial CD4 counts were plotted for each patient and the straight line that best fitted was obtained using least squares regression. Differences in rate of decline were tested using analysis of variance, after each patient was weighted by the reciprocal of the variance. RESULTS: Baseline levels of percentages of CD8+CD38+ T lymphocytes predict the CD4 decline in HIV-1-infected patients. Within the CD8+ subset, the primed CD8+CD38+CD45RO+ population was responsible for this prediction. Conversely, the naive CD8+CD38+CD45RA+ population was not predictive. Patients who initially showed a percentage of CD8+CD38+ T lymphocytes above the median (> 25%) had a more marked decline in CD4+ T cells when compared to individuals with percentages of CD8+CD38+ T lymphocytes below the median value (79.3 and 21.2 x 10(6)/l mean CD4 cell decline per year, respectively). Similarly, percentages of CD8+CD38+CD45RO+ T cells above the median value (> 7%) were also associated with a more rapid decline (69.4 and 14.2 x 10(6)/l mean CD4+ cell decline per year). These results were statistically significant after adjustment for the baseline CD4 count and beta 2-microglobulin levels. CONCLUSIONS: Percentages of activated CD8+ cells expressing CD38+ can predict the rate of decline (slope) of the CD4+ T cells. This resides in the CD45RO+ primed population. An early prediction of the CD4+ slope will allow the clinician to target treatment to those patients that are most likely to benefit.