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Biomedical subjects

E L Franco

Publications and source records attributed to E L Franco.

At least 73 records · Page 4Linked to original sources

Epidemiologic correlates of cervical neoplasia and risk of human papillomavirus infection in asymptomatic women in Brazil.

To investigate whether the epidemiologic correlates of cervical cancer are predictors of infection with genital human papillomavirus (HPV), we performed a prevalence survey in two metropolitan areas of Brazil, Recife and São Paulo. The data records of four randomly selected HPV-negative women were matched on the basis of age, clinic, and admission period with those of each of 136 patients with positive HPV DNA hybridizations. Anal intercourse [prevalence rate ratio (PRR) = 1.7] and current pregnancy (PRR = 2.3) were the only variables associated with HPV 6/11 infection (P less than .10). Only the frequency of gynecologic consultations was associated (negatively) with risk of HPV 16/18 infection (P = .0175). Our data failed to provide evidence for the existence of shared risk factors for genital HPV infection and cervical cancer. The frequency of mixed HPV infections was 13 times higher than expected, a finding suggestive of the existence of additional determinants of HPV infection not akin to the general behavioral characteristics of women that are probed in the study.

Adult↗

Tumor and serum beta-2-microglobulin expression in women with breast cancer.

To investigate whether the tumor expression of beta-2-microglobulin (beta 2-M) could serve as a marker of tumor biologic behavior, the authors studied specimens of breast carcinomas from 60 consecutive female patients. Presence of beta 2-M was analyzed by immunohistochemistry. No significant correlations were found between tumor beta 2-M expression and several histologic attributes such as type, histologic and nuclear grades, mitotic index, necrosis, vascular invasion, and lymphocytic infiltration. Likewise, beta 2-M was not associated with markers of disease extension such as TNM, (UICC, classification of malignant tumors) staging and axillary lymph node involvement or with estrogen, progesterone, and glucocorticoid receptor levels. However, there was a significantly positive association between tumor beta 2-M expression and the degree of lymphocytic infiltration in the tumor tissue. Beta 2-M serum levels were determined by an enzyme-linked immunosorbent assay in samples from 22 of the above women. Although some of the highest values had been obtained in women with larger (T4) primary tumors, the authors failed to detect any statistical relationship between beta 2-M expression in the tumor with serum levels or between serum beta 2-M and the above histologic, laboratory, and clinical factors.

Adult↗

Epidemiologic programs for computers and calculators. A microcomputer program for multiple logistic regression by unconditional and conditional maximum likelihood methods.

A frequent procedure in matched case-control studies is to report results from the multivariate unmatched analyses if they do not differ substantially from the ones obtained after conditioning on the matching variables. Although conceptually simple, this rule requires that an extensive series of logistic regression models be evaluated by both the conditional and unconditional maximum likelihood methods. Most computer programs for logistic regression employ only one maximum likelihood method, which requires that the analyses be performed in separate steps. This paper describes a Pascal microcomputer (IBM PC) program that performs multiple logistic regression by both maximum likelihood estimation methods, which obviates the need for switching between programs to obtain relative risk estimates from both matched and unmatched analyses. The program calculates most standard statistics and allows factoring of categorical or continuous variables by two distinct methods of contrast. A built-in, descriptive statistics option allows the user to inspect the distribution of cases and controls across categories of any given variable.

Algorithms↗

Age and lateness of referral as determinants of extra-ocular retinoblastoma.

The risk of extra-ocular (EO) vs. intra-ocular disease was evaluated in a retrospective study of 158 consecutive cases of retinoblastoma (age range: birth to 113 months) admitted to the A.C. Camargo Hospital, Brazil, between January 1975 and December 1985. The risk of having EO disease was strongly dependent on the age at diagnosis and lateness of referral. The older the child at first admission the higher the risk of finding EO disease at diagnosis. This association was considerably more pronounced among sporadic unilateral cases. Patients with a history of longer duration of symptoms were more likely to exhibit EO disease than patients seeking medical attention within six months of the onset of the disease. This association seemed to be confounded by the genetic form of the disease as the increase in risk of EO disease appeared later among the germinal cases. Clinical stage and lateness of referral were the variables most associated with the survival experience of patients.

Age Factors↗

Evaluation of serological diagnostic indices for mucocutaneous leishmaniasis: immunofluorescence tests and enzyme-linked immunoassays for IgG, IgM and IgA antibodies.

The sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of immunofluorescence (IF) and enzyme-linked immunoassays (ELISA) for IgG, IgM and IgA antibodies were assessed on sera from mucocutaneous leishmaniasis patients and controls. The sensitivity of the IgG-ELISA test was 93.3% with 95% confidence interval higher than what could be due to a random test not associated with the disease. The specificity of all tests, except the IgM-ELISA, gave indices that could not have been due to chance. The IgG-ELISA and IgG-IF had the highest positive predictive value and the kappa statistic showed that the strength of agreement between the disease and the test was strongest for IgG-ELISA. The IgG-ELISA had a negative predictive value with 95% confidence limits that were not due to chance alone. Efficiency was highest for IgG-ELISA and IgG-IF. These results were obtained using sera from patients with severe or long-standing disease and from controls in whom the disease was ruled out by a negative Montenegro skin test. In field surveys where the differences between cases and controls are less easy to define the diagnostic indices of these tests may vary with the disease prevalence.

Adolescent↗

Factors of prognostic importance in childhood non-Hodgkin's lymphoma treated with two modified LSA2-L2 protocols. A multivariate analysis approach.

The results of therapy given to 74 children with advanced disease, abdominal non-Hodgkin's lymphoma were retrospectively evaluated with respect to the major prognostic factors related to disease outcome. The first 36 patients admitted in the study were treated with a modified LSA2-L2 protocol, and the remaining patients received the same regimen with the addition of intermediate-dose methotrexate (MTX) intravenously during the induction phase (LSA2-L2-MTX). The last ten patients admitted were given a leucovorin rescue along with the administration of MTX. The relative efficacy of the LSA2-L2-MTX over the baseline LSA2-L2 regimen was analyzed by multivariate statistical methods taking into consideration several candidate coprognostic factors. The risk of treatment failure was substantially reduced (55%) with the use of the LSA2-L2-MTX regimen. Rescue with leucovorin did not contribute a further significant gain in treatment efficacy, although fewer toxicity-related problems were observed as compared to the no-rescue period. Five prognostic factors emerged as significantly explanatory of the risk of treatment failure in addition to protocol type: lymphocyte count, disease stage, surgical debulking, sex, and nutritional status. Based on these variables, a logistic regression equation could be derived to identify groups that were at risk for treatment failure.

Abdominal Neoplasms↗

Plasminogen activator expression and steroid hormone receptors in female breast cancer: a multifactorial study.

In order to evaluate the relationship of plasminogen activator (PA) activity to the expression of estrogen (ER) and progesterone (PR) receptors, we assayed primary tumor specimens from 121 cases of female breast cancer. Other clinical and histopathological variables were also investigated with respect to their possible association with PA activity in the samples. Statistical correlations were examined by stratified analysis techniques and by multiple regression methods. PA activity was higher in tumors which were ER+PR+ than in those exhibiting other subsets of joint receptor expression, a finding which was particularly predominant in tumors from post-menopausal women. Of the other variables examined, only disease stage, nodal status and vascular infiltration presented marginal positive statistical associations with PA activity, although this was not confirmed by multivariate analysis. The latter technique showed that the presence of PR was sufficient to explain the variation in PA levels. However, ER emerged as the sole significantly explanatory factor when ER+PR- patients were removed from analysis. Both PR and age (negatively) were independent contributory factors for PA activity in the analysis of post-menopausal women. None of the variables examined emerged as being significantly associated with PA when data from pre-menopausal patients were used. These findings indicate that PA activity in breast tumor samples is statistically associated with the expression of functional estradiol receptors, although to a lesser extent than PR.

Adult↗

Correlation patterns of cancer relative frequencies with some socioeconomic and demographic indicators in Brazil: an ecologic study.

Sex-specific relative frequencies (RF) of oral, esophageal, stomach, colon, rectal, laryngeal, lung, female breast, cervical and penile cancers obtained from a government-sponsored, nation-wide data base of histopathological diagnoses were evaluated with respect to all possible inter-site correlations and with 12 socioeconomic and demographic variables for 23 States in Brazil. Use of bivariate and multivariate methods detected a high positive intercorrelation among RFs of lung, laryngeal and colon cancers regardless of sex. RFs for these 3 sites were also positively correlated with many markers of State development and affluence. Cervical and penile cancers emerged as a distinct subset with respect to their correlation patterns. RFs for these neoplasms were highly (positively) correlated (r = 0.8606, p less than 0.001) with each other and exhibited intense negative associations with many of the affluence markers and the former cancer sites. Bivariate correlations generally exhibited a better fit with female-specific RFs than with data from males which was reflected in the number of strong correlations detected by sex.

Brazil↗

Catching up with history: treatment of Wilms' tumor in a developing country.

Despite the tremendous progress that pediatric oncology has achieved in the treatment of Wilms' tumor over the last several decades, survival rates in our institution before 1970 did not exceed 8%. In order to correct the problem standardized therapy was instituted in 1970 through a multimodal oncological team. Results using the new approach were reviewed in 1979 (50 patients) and showed an overall 34% 2-year survival rate. Although encouraging, these results were still far below the ones reported in the literature. This prompted us to use a vigorous professional and lay educational program in the city. Treatment methods were replaced by those advocated by the Second National Wilms' Tumor Study. A second evaluation period initiated in 1979 and extended through 1984 (35 patients) yielded an overall 83% survival rate. A retrospective study of the two periods by univariate and multivariate survival analysis revealed that, although much of the improvement in survival could be attributed to a shift in stage distribution towards earlier disease, the admission period itself had an important additional explanatory effect with respect to survival. This was probably due to the improvement in treatment protocols used in the latter period. Age was a prognostic variable only for patients admitted during the 1979-1984 period.

Actuarial Analysis↗

Androgen, estrogen, and progesterone receptor levels in malignant and benign breast tumors: a multivariate analysis approach.

Androgens have been frequently used in the treatment of breast cancer. However, objective responses seem to vary according to the steroid hormone receptor expression of the tumor. We have studied the relationship between concentrations of androgen receptors (AR) and those of estrogen (ER) and progesterone (PR) receptors by multiple regression and stratified analysis techniques in 154 cases of primary breast carcinomas and 39 cases of benign tumors. Both the proportion of AR-positive tumors and the concentration of AR were dependent upon the coexpression of ER and PR by the specimens. This association was evident for malignant tumors with predominance of the positive correlation between AR and ER over that of AR and PR in post-menopausal patients. In premenopausal women, ER and PR concentrations were similarly correlated with AR levels. The PR, but not the ER concentration, was positively correlated to AR levels in benign breast tumors. These findings were confirmed by multiple regression, taking into consideration additional information about the patients to build statistical models allowing prediction of AR. Among the other variables considered in building these models--age, menopausal status, weight, height, and clinical stage--only height (using data from all patients) and age (data from post-menopausal women) emerged in addition to ER and PR as significantly explaining the variability of AR as the dependent variable.

Adult↗

Sensitivity, specificity, and predictive value of laparoscopy for the staging of gastric cancer and for the detection of liver metastases.

Three hundred and sixty patients with gastric carcinoma were evaluated by laparoscopy. The following tumor attributes were used in the staging workup: serosal infiltration, tumor fixation, metastasis to lymph nodes, peritoneal dissemination, and liver metastasis. For the detection of liver metastases, subgroups of these patients were also tested by liver scintigraphy, ultrasonography, and serum alkaline phosphatase determination. Use of diagnostic indexes with their confidence intervals provided an objective means of assessing performance for the various combinations of tests and attributes. The attributes which were most accurately detected by laparoscopy were peritoneal dissemination and liver metastases with 89.4% and 96.5% efficiency, respectively. Laparoscopy was a superior diagnostic method when compared to the other tests for detection of liver involvement. Scintigraphy and ultrasonography presented comparable sensitivities, 78.7% and 78.6%, respectively (as opposed to 87.2% of laparoscopy), but the former yielded a high rate of false-positive results, 62.6%. Detection of liver metastases by assaying alkaline phosphatase levels was the least sensitive diagnostic alternative examined.

Adult↗

Epidemiologic programs for computers and calculators. Simple algorithms for the representation of deterministic and stochastic versions of the Reed-Frost epidemic model using a programmable calculator.

Two programs are described for the emulation of the dynamics of Reed-Frost progressive epidemics in a handheld programmable calculator (HP-41C series). The programs provide a complete record of cases, susceptibles, and immunes at each epidemic period using either the deterministic formulation or the trough analogue of the mechanical model for the stochastic version. Both programs can compute epidemics that include a constant rate of influx or outflux of susceptibles and single or double infectivity time periods.

Computers↗

Evaluation of dot enzyme-linked immunosorbent assay for mucocutaneous leishmaniasis and comparison with microplate enzyme immunoassay.

A dot enzyme-linked immunosorbent assay (dot ELISA) was evaluated and compared with a standard microplate ELISA (immunoglobulin G [IgG] ELISA) for the serological diagnosis of mucocutaneous leishmaniasis. The two assays were used to test 113 serum specimens from the following groups: normal individuals and patients with deep mycoses, toxoplasmosis, mucocutaneous leishmaniasis, visceral leishmaniasis, Chagas' disease, malaria, and schistosomiasis. Both tests exhibited cross-reactivity when testing specimens from cases of visceral leishmaniasis and Chagas' disease. The dot ELISA proved to be economical with respect to use of reagents and was easy to perform. Interpretation could easily be made by visual inspection of reaction endpoints in the nitrocellulose disks, obviating the need for spectrophotometric readings. There were no significant differences in sensitivity between the dot ELISA and the IgG ELISA at a cutoff level either of 20 or 40. However, its most remarkable feature was the high specificity compared with that of the IgG ELISA. Because of its ease of performance and high sensitivity and specificity, the dot ELISA should be an excellent test to be executed in the field during seroepidemiological surveys.

Cross Reactions↗

An oocyst-transmitted outbreak of toxoplasmosis: patterns of immunoglobulin G and M over one year.

Sera from 32 patients who became ill after jungle combat training were tested for antibodies to Toxoplasma gondii using the indirect immunofluorescence test. Swift rises of both IgG and IgM antibodies occurred within 2 weeks of infection. Reduction in IgM titers, due to competitive suppression by IgG antibody, occurred in most but not all cases. Suppression of IgM reaction by IgG antibody could be prevented by adsorption of serum with Staphylococcus aureus containing protein A. Antibody of the IgM class could be detected at greater than or equal 1:256 level in many sera at 6-month and 1-year intervals after exposure. In groups with exposures such as were experienced in this study, the presence of IgM antibody titers in single serum specimens cannot be used to indicate recent exposure. Both IgG and IgM antibody may rise together to high levels very rapidly after infection; IgM did not precede IgG antibody in our 32 subjects.

Adolescent↗

Computer-assisted multiple categorization of absorbance values in ELISA through pictorial emulation of 96-well plates.

A simple algorithm is proposed by which multiple categorization of absorbance values from ELISA plates is performed under a microcomputer control. The printed output is a pictorial emulation of a 96-well plate with the color intensities represented for each reaction. Although the method is presented as a colorimeter computer interfaced system, a provision for manual entry of absorbance values via keyboard is also included. Simulation is based solely on the magnitude of absorbance values. Therefore, it is possible to utilize any enzyme/substrate combination within the range of filters of the colorimeter. We have tested the present system for titration of anti-malarial antibodies in human serum and for the screening of mouse hybridoma culture supernatants.

Absorption↗

Monoclonal antibody characterization of Plasmodium falciparum antigens.

We characterized a set of eight monoclonal antibodies produced against Plasmodium falciparum. In an indirect fluorescent antibody assay the antibodies produced small dots of fluorescence in schizonts and individual merozoites. This merozoite-associated dot reactivity occurred with 21 different strains of P. falciparum, but there was no reactivity with other human, nonhuman primate, or rodent Plasmodium species. Three of the monoclonal antibodies precipitated proteins of Mr 145,000, 135,000, and 104,000. Five of the monoclonal antibodies precipitated proteins of Mr 78,000, 63,000, 42,000, and 40,000.

Antibodies, Monoclonal↗

Use of monoclonal antibodies in an enzyme immunoassay for factor VIII-related antigen.

Two monoclonal antibodies (MAb 53, MAb D7) were produced, each having specificity for Factor VIII-related antigen (FVIIIR:Ag), but exhibiting no inhibitory effect on either procoagulant activity or the ability of von Willebrand factor to agglutinate platelets in the presence of the antibiotic ristocetin. For quantification of FVIIIR:Ag, we used the antibodies in a competitive enzyme-linked immunosorbent assay (ELISA). Binding of either of the MAb's to solid-phase antigen was inhibited by free FVIIIR:Ag in the test sample. Dose-response curves for the reference standards were consistently linear (r2 greater than 0.990) and reproducible. The normal range of FVIIIR:Ag detected in plasma (normal defined as 1000 units/L) was similar to that reported for polyclonal heterologous antibodies in similar ELISA or immunoradiometric (IRMA) systems, and the assay was sensitive to 10 units of FVIIIR:Ag per liter. Inter- and intra-assay precision was good, coefficients of variation being less than 11%. Studies on patients showed good correlations between values measured by MAb ELISAS and IRMA (polyclonal rabbit antibody) over FVIIIR:Ag concentrations ranging from less than 10 to 2700 units/L (r = 0.971, p less than 0.001 for MAb 53; r = 0.938, p less than 0.001 for MAb D7). Both ELISAS could be used to quantify FVIIIR:Ag in other mammalian species. The assay is inexpensive and simple, and all reagents required for it are commercially available.

Antibodies, Monoclonal↗

Diagnosis of acute acquired toxoplasmosis with the enzyme-labelled antigen reversed immunoassay for immunoglobulin M antibodies.

The reversed enzyme-labelled antigen immunoassay (R-EIA), based on the capture of serum immunoglobulin M antibodies (IgM) and subsequent addition of Toxoplasma gondii soluble antigen tagged with peroxidase and substrate, was evaluated comparatively with the IgM-indirect immunofluorescence test (IgM-IIF) for the detection of anti-toxoplasma IgM antibodies in sera from individuals with diagnosed acute acquired toxoplasmosis. Additional serum groups from normal healthy individuals and sera presenting possible nonspecific reactivities were also evaluated. Complete specificity of R-EIA was shown. There was no correlation between the magnitude of R-EIA results and IgM-IIF titers, but a positive (although not linear) correlation was found between R-EIA and the IgM-IIF titers obtained after adsorption of sera with Staphylococcus aureus protein A. Direct labelling of the antigen by a simple coupling technique facilitated the assay standardization and improved its signal-to-noise ratio.

Acute Disease↗