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Biomedical subjects

P Herrera

Publications and source records attributed to P Herrera.

16 recordsLinked to original sources

Expression of a tumor necrosis factor alpha transgene in murine pancreatic beta cells results in severe and permanent insulitis without evolution towards diabetes.

Mice bearing a tumor necrosis factor (TNF) alpha transgene controlled by an insulin promoter developed an increasingly severe lymphocytic insulitis, apparently resulting from the induction of endothelial changes with features similar to those observed in other places of intense lymphocytic traffic. This was accompanied by dissociation of the endocrine tissue (without marked decrease in its total mass), islet fibrosis, and the development of intraislet ductules containing, by places, beta cells in their walls, suggesting a regenerative capacity. Islet disorganization and fibrosis did not result from lymphocytic infiltration, since they were also observed in SCID mice bearing the transgene. Diabetes never developed, even though a number of potentially inducing conditions were used, including the prolonged perfusion of interferon gamma and the permanent expression of a nontolerogenic viral protein on beta cells (obtained by using mice bearing two transgenes). It is concluded that (a) a slow process of TNF release in pancreatic islets induces insulitis, and may be instrumental in the insulitis resulting from local cell-mediated immune reactions, but (b) that insulitis per se is not diabetogenic, lymphocyte stimulation by cells other than beta cells being necessary to trigger extensive beta cell damage. This provides an explanation for the discrepancy between the occurrence of insulitis and that of clinical disease in autoimmune diabetes.

Animals

[Typhoid fever in children: association with blood phenotypes ABO, Rh and MNSs].

The hypothesis that blood phenotype B is associated to typhoid fever either directly or interacting with other phenotypes of the Rh or MNSs blood systems was tested. 256 children from the Northern Area of Santiago (Chile) with bacteriologically confirmed typhoid fever and 329 afebrile controls matched by age and gender from the same population, were studied. Association was found between phenotype RH3 and protection against disease for the whole group (OR = 0.67; p < 0.042) and for males (OR = 0.05; p = 0.014) although the gender-RH3 interaction was at the limit of significance. RH8 and Ss phenotypes were associated to increased susceptibility (OR = 1.83; p < 0.034 and OR = 1.56; p = 0.01, respectively). Controlling RH3 and Ss phenotypes by B, increased their effects (OR = 0.26; p = 0.04 and OR = 3.42; p = 0.026, respectively), but interactions did not reach statistical significance. These results show a susceptibility cline whose implications and applicability deserve further studies. A high proportion of S. paratyphi B (23.8%) appeared in this series, which may imply sample heterogeneity. The meaning of these findings need further epidemiological and genetic studies.

Blood Group Antigens

[Study of the Widal test phenotypic expression of blood groups ABO, Rh and MNSs in patients with typhoid fever].

The significance of the Widal test (WT) as a phenotypical expression was investigated in a cross-sectional study of 244 children from the Northern Area of Santiago (Chile) with bacteriologically confirmed typhoid fever (TF) due to S. typhi (183 cases) and S. paratyphi B (61 cases). The working hypothesis was that if the parasite-host relationships were similar for these two agents the immune response, as measured by the Widal test, should be similar. An association between test response and etiology was found consisting of a significantly higher proportion of positive response, in cases due to S. paratyphi B as compared with those due to S. typhi, (OR = 2.13; 95 Cl% = 1.06, 4.32; p = 0.02). Stratified analysis showed that although the association between etiologic agent and Widal test response persisted within all strata, significant interactions could be shown as evidenced by the magnitude of the associations, which varied according to blood phenotypes as well as gender (Mantel-Haenszel test for heterogeneity for 0, p < 0.034; for RH5 p < 0.033; for SS, ss p < 0.056; and gender p < 0.033). These results support the hypothesis that the Widal test response is a phenotypical marker eventually useful for studying human genetic heterogeneity in typhoid fever. The implications of these findings regarding previous study results and the possible role of S. paratyphi B in typhoid fever and its related conditions are discussed.

Adolescent

[Paratyphoid B fever in 2 areas of Santiago. An analysis of the epidemiological significance].

Salmonella isolates from 3920 patients with typhoid fever from 2 areas in Santiago were analyzed to determine the frequency of association with S paratyphi B infection. This was demonstrated in 18.8% of subjects in both areas, a figure significantly higher than the 8-10% previously reported. The association with S paratyphi B was higher for females, especially for the younger age group. These findings suggest an infectious agent-gender-age interaction which may explain the discrepancy with previously reported rates of infection. Their possible relation to the chronic salmonella carrier state and association with biliary tract lithiasis and cancer is discussed.

Adolescent

Nutritional status assessment of HIV-positive drug addicts.

Since human immunodeficiency virus (HIV) is known to lead to modifications of immune function and interrelationships among malnutrition, anergy and drug addiction have been shown, the aim of this work was to assess the nutritional status of 36 male heroin addicts under a period of detoxication (3 months). They were divided into two groups: (1) HIV negative (n = 20) and (2) HIV positive (n = 16); heights, weights and serum albumin concentration were measured and immune function was tested, using delayed hypersensitivity skin tests containing 7 antigens. No significant differences in anthropometric measurements were found between both groups, but anthropometric improvement was shown in every patient after the detoxication period. Serum albumin, often used as a classical index of malnutrition, remained within the normal values in both groups. The whole response to skin tests was depressed in both groups and no significant differences were shown between them. Therefore, these results might suggest that in spite of the apparent anthropometric recovery and the normal values of albumin, a subclinical malnutrition was indicated by the depressed immune function, which was more noticeable in the HIV-positive group.

Adult

Correlation between EEG and cognitive abilities: sex differences.

EEG activity was recorded during rest in 9 male and 9 female volunteers, aged 23 and 27, from C3, C4, T3, T4, P3, P4, O1 and O2, referenced to the ipsilateral earlobe. In a separate session verbal, spatial and abstract reasoning subtests of the Differential Aptitude Test were administered. Samples of EEG activity of 20.48 s were analysed and the interhemispheric correlation was obtained. Interhemispheric correlation in the alpha band was significantly higher in women than in men at central, parietal and occipital derivations. Significant correlations were found between D.A.T. scores and interhemispheric correlation, positive for women with abstract and spatial aptitudes in the central cortex, and negative for men with spatial, abstract and verbal scores in most derivations recorded. The opposite sign of men and women's correlations suggests the existence of a different cerebral functional organization, women showing lower hemispheric differentiation than men.

Adult

Glucose stabilization and coronary infarction with artificial pancreas in heart-lung preparation.

In the performance of heart-lung preparations, after 4-8 hours, it is an usual feature to have multiple microinfarctions, and, finally, heart failure and ventricular fibrillation. We have studied glucose, triglycerides and conjugated fructose consumption by the heart-lung preparation and found a very fast glucose depletion (30 to 90 minutes to glucose 0, starting with glucose 120 mg/dl). The depletion has been slower for triglycerides and even slower for conjugated fructose. Ventilation with pure oxygen has not modified itself the coronary deterioration, but if a Biostator has been used in order to maintain the glucose levels at 100-110 mg/dl., the isolated heart-lung does not deteriorate in 16-24 hours, nor show electrical signs of coronary impairment; after this time, the respirator is disconnected and the preparate discarded. The above mentioned experiments demonstrated the need of artificial control of glycemia in isolated organ experiments and suggest the convenience to use more widely the artificial pancreas (Biostator in our case) for better treatment no only in diabetic or pancreatic patients, but also in many circumstances in which the glucose utilization is impaired.

Animals

[Genetic factors in typhoid fever].

The study of genetic factors associated to infectious diseases is a promising research field for optimizing their management and control in the future. For typhoid fever, one of our major health problems, this approach has been sporadic an fruitless for having been addressed to disease's overall susceptibility. Moreover, difficulties on recognition of clinical sub-sets have prevented definition of unambiguous clinical phenotypes appropriate for this objective. With the aim of finding the basis for phenotypes identification, or definite disease expressions, a search including foreign and national literature was carried out for the 1960-88 period. From animal experimentation, human immunogenetics, epidemiology and clinical literature, data was obtained for proposing five phenotypes: the incubation period, typhoid relapse, agglutinins response (Widal's test), response to vaccination and metabolic behaviour of certain substances, including antibiotics. That one or more of these phenotypes and their possible association with polymorphic systems might lead to populational subsets recognition in typhoid fever is suggested.

Animals

[Widal reaction and phenotypes in children with typhoid fever (preliminary study)].

Recognition of genetic heterogeneity in typhoid fever patients might allow studies on the behaviour of definite cohorts regarding this infection, which would be important for clinical and epidemiological purposes. Under the hypothesis that agglutinins response (Widal test) is a suitable phenotype for this objective, associations between results of this response at admission (positive and negative) and clinical and hematological variables were explored in 91 children with bacteriologically confirmed typhoid fever, admitted to a metropolitan hospital at Santiago, Chile, during 1981-82 period. Association between gender and negative Widal test was found in males when this test was performed during the third week of disease (OR = 10, p = 0.52) as well as a tendency of females to express figures below the mean for total WBC count in patients older than 10 years (OR = 2.43, p = 0.019) and for neutrophils (%) in younger than this age when the Widal test was negative in the latter (OR = 10, p = 0.016). These preliminary findings suggest that Widal test and gender might interact for determining the presumptive heterogeneity in this children group.

Age Factors

[Pleural empyemas in children due to Hemophilus influenzae].

22 consecutive cases of pleural empyema due to H. influenzae in children are reported. An increment of its incidence during the 1975-76 period is observed. All cases were in children under 3 years of age, with a mean of 15.5 months. The presenting syndrome at admission was varied. In 50% of cases, pleuropulmonary infection was ignored. Nearly one half of cases of pleural empyema due to H. influenzae had simultaneous purulent meningitis caused by the same microorganism. This type of empyemas, though having a prolonged evolution, apparently appear to have a good prognosis, compared with that produced by S. aureus. There are some differences, being the most outstanding: low frequency of pyoneumothorax and the lack of radiological evidences of abscesses and or pneumotoceles, in any phase of the clinical course. Stress is placed on the value of the bacteriological study of blood and CSF in children under 3 years of age with pleural empyema. A high rate of positive blood cultures was found. (75%). Pieuropulmonary complications, as a frequent event during severe infections (septicemic disease) due to H. influenzae is considered. A clinical characterization of children in whom a pleural empyema could occur is proposed. A discussion is made about diagnostic, therapeutic and prognostic implications of these complications.

Cerebrospinal Fluid