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Biomedical subjects

L Valdivia

Publications and source records attributed to L Valdivia.

At least 19 recordsLinked to original sources

[Measurement of 17 OH progesterone in blood in Chilean newborns: antecedents for implementing a grogram for the neonatal detection of congenital adrenal hyperplasia].

BACKGROUND: The early diagnosis and therapy of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can prevent adrenal crises and erroneous gender assignment in affected newborns. To achieve this goal neonatal mass-screening programs have been developed, measuring blood 17 alpha-hydroxyprogesterone (17OHP). In Chile there is no experience with this type of screening. AIM: To develop a method for measuring 17OHP in filter paper blood specimens. To obtain reference ranges and determine neonatal 17OHP threshold levels according to gestational age and birth weight. To analyze factors affecting the cost-efficiency ratio and suggest recommendations for the organization of a neonatal screening program for CAH in Chile. MATERIAL AND METHODS: Nine hundred twenty two newborns were studied. 17OHP was measured using double antibody radioimmunoassay in filter paper blood samples obtained 48 h after birth. Reference ranges were determined according to gestational age and birth weight and a cutoff point of 25 ng/ml was established. RESULTS: Seventeen newborns had 17OHP over the cutoff value. They were assessed by a pediatric endocrinologist and in none of them, CAH was confirmed. Therefore the false positive rate of the determination was 1.8%. Among these newborns with elevated 17OHP, 66% had a birth weight below 1.5 kg and 5.8%, a birth weight between 1.5 and 2.5 kg. The cost per reported result was US $ 1. Timing of the recall was between the 3 and 10 days of life. No newborn missed the follow-up. DISCUSSION: To increase the cost-efficiency ratio of an eventual neonatal screening program, newborns with birth weights below 1.5 kg should be excluded and cutoff points should be defined according to birth weight (Rev Méd Chile 2000; 128: 1113-18).

17-alpha-Hydroxyprogesterone↗

A new double-stranded RNA mycovirus from Botrytis cinerea.

A simple double-stranded RNA mycovirus was detected in a wild-type Botrytis cinerea 55k strain. The virus was located in the fungus cytoplasm as free particles of approximately 28 nm in diameter. The mycovirus possesses a single double-stranded genome segment of 1.8 kilobase pairs (kbp) encapsidated within an isometric protein coat whose main structural component is a polypeptide of 68 kDa. Cells infected with this virus showed an important degree of cellular degeneration.

Botrytis↗

[Detection of thyroglobulin autoantibodies and potential interference with serum thyroglobulin measurement].

BACKGROUND: Thyroglobulin measurement is useful for the follow up of patients subjected to total thyroidectomy for differentiated thyroid carcinoma. Thyroglobulin autoantibodies may interfere with its determination. AIM: To measure thyroglobulin autoantibodies and their interference with thyroglobulin determination. MATERIAL AND METHODS: The presence of thyroglobulin autoantibodies was investigated in 801 serum samples sent to the laboratory for measurement of thyroglobulin levels. A serum was considered positive for these autoantibodies when radioactivity corresponding to 125I-thyroglobulin bound to thyroglobulin autoantibodies, precipitated with human gamma globulin, exceeded in 1.4 times that of a negative sera pool. In positive sera, thyroglobulin autoantibody concentration was measured and its interference with thyroglobulin radioimmunoassay was assessed through a recuperation test using exogenous thyroglobulin. RESULTS: Thyroglobulin autoantibodies were detected in 149 sera (18.6%). Of these, 65 had a recuperation that fluctuated between 1 and 80%. Thyroglobulin autoantibody concentration was negatively correlated with recuperation percentages (r = -0.64; p < 0.001) but not with thyroglobulin concentrations (r = 0.08). Thyroglobulin was higher in positive sera with a recuperation over 80% than in sera with a recuperation of less than 80% (12.7 +/- 1.7 and 5.9 +/- 0.6 ng/ml, respectively; p < 0.001). CONCLUSIONS: Thyroglobulin autoantibodies interfere with thyroglobulin measurement by radioimmunoassay, sequestering variable amounts of thyroglobulin. The presence of these autoantibodies must be investigated prior to thyroglobulin determination.

Autoantibodies↗

Amelia: analysis of its epidemiological and clinical characteristics.

Eighteen cases of amelia in the Spanish Collaborative Study of Congenital Malformations (ECEMC) were analyzed epidemiologically. Prevalence at birth was 0.15 per 10,000 newborn infants, which is not different from that reported by other authors. Affected females outnumbered males. When compared with the control group, a lower birth weight, shorter gestation, lower placental weight, greater frequency of single umbilical artery, noncephalic presentation at birth, and more frequent maternal vaginal bleeding were observed in amelia cases. There were no significant variations of parental age. None of these patients was exposed to known teratogens, apart from 1 born to a diabetic mother; 3 patients had a genetic condition. Comparison of these variables with other studies is difficult because there is only one study that specifically analyzed amelia. Our data together with previous observations suggest that the genetic basis of amelia might be more important than has been considered previously.

Birth Weight↗

Heat shock protein reactivity of lymphocytes isolated from heterotopic rat cardiac allografts.

Although it is well known that cellular rejection is mediated by alloreactive lymphocytes, several investigators, including our group, have shown that such cells are a rather small proportion of the T cell infiltrate of the alolograft. We have therefore postulated that graft-infiltrating lymphocytes must recognize other antigens. Since heat shock protein (hsp)-specific lymphocytes have been shown to participate in several autoimmune diseases and in tumor immunity, we hypothesized that hsp-reactive lymphocytes are involved with allograft rejection. This hypothesis was tested with a rat model of heterotopic MHC-incompatible cardiac allografts (ACI into Lewis), whereby graft-infiltrating lymphocytes and spleen cells were tested in vitro with different recombinant mycobacterial hsp preparations. As expected, allograft lymphocytes showed proliferative responses to irradiated spleen cells from the donor. This proliferation was markedly augmented by hsp65 (3-fold) and hsp70 (5-fold), whereas hsp10 and the protein control ovalbumin had no effect. Proliferation of allograft lymphocytes to hsp in context with syngeneic splenocytes as antigen-presenting cells (APC) was seen primarily if small quantities of IL-2 had been added to the cultures. In contrast, hsp-specific proliferation was never observed with syngraft lymphocytes, even after addition of IL-2. Spleen cells from allograft and syngraft recipients showed hsp augmentation of alloproliferation, but the magnitude was less than that with allograft lymphocytes. Kinetic studies showed that hsp-reactive lymphocytes first appeared in the allograft on day 3 posttransplant. Tacrolimus immunosuppression of transplant rejection prevented the appearance of hsp-reactive lymphocytes in allografts. Culture conditions have been established to generate hsp65- and hsp70-specific T lymphocyte lines and clones from allograft-infiltrating cells. These cultured cells exhibited hsp reactivity only in context with self-APC, and this was augmented by small amounts of IL-2. These data provide strong evidence for the involvement of hsp-reactive lymphocytes in allograft rejection. We propose the concept that during rejection tissue stress induced by alloreactive effector lymphocytes promotes the recruitment and activation of hsp-reactive lymphocytes, especially in the presence of IL-2 released into the allogeneic environment of the transplant. These hsp-reactive T cells may play a role in the immune cascade of the inflammatory process of transplant rejection.

Animals↗

Expression of stress proteins and lymphocyte reactivity in heterotopic cardiac allografts undergoing cellular rejection.

This report addresses the concept that, during rejection, the allograft undergoes a stress response which leads to an increased expression of stress proteins, also called heat shock proteins (hsp), and the recruitment and activation of hsp-reactive lymphocytes. Recent studies in our laboratory have provided evidence that hsp-reactive T-cells are present in cardiac allografts undergoing rejection. In this study, an MHC incompatible heterotopic heart allograft model (ACI into LEW) was chosen to analyse the kinetics of hsp expression during the development of rejection. Allografts and syngrafts (LEW into LEW) were harvested every day during the first 5 days post-transplant. Immunoblot analysis of proteins extracted from graft stromal tissues was done with murine monoclonal antibodies (mAb) against various mammalian hsp. Proliferation studies were done to determine hsp reactivity of graft-infiltrating lymphocytes on different days post-transplant. Three types of stressful stimuli appeared to increase hsp expression in the allograft. The first was a physiological stress secondary to the trauma of the transplant procedure and ischaemia/reperfusion injury and this would occur in allogeneic and syngeneic grafts. During the first day after transplantation, both types of grafts showed higher expression of hsp72 and grp78 and to a lesser extent, hsp60 and grp75. On the second and third day, the expression of grp78 and grp96 was higher in allografts than in syngrafts and this may reflect an immunologically mediated stress response in the allograft when infiltrating hsp-reactive lymphocytes became first detectable in the allograft. The third type of stress appeared related to the inflammatory process associated with rejection. On the fourth and fifth day post-transplant, the allografts showed strong expression of at least five proteins of lower molecular mass reacting with hsp-specific mAbs; namely, approximately 40 kDa (detected by anti-hsp60), approximately 30 kDa (by anti-hsp72), approximately 45 kDa and approximately 32 kDa (by anti-hsp72 + hsc73), and approximately 50 kDa (by anti-grp78). At that time, the allograft began to show progressive inflammatory changes and tissue damage. The appearance of lower molecular mass hsp-crossreactive proteins might reflect a degradation of hsps which had increased expression earlier during the post-transplant period. This process may generate large quantities of hsp-derived peptides which may be presented by MHC molecules to graft-infiltrating T-cells. Another interpretation of the strong expression of lower molecular bands in later allografts is that they represent other stress proteins that crossreact with antibodies against hsp60 and hsp70 family members.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Hamster-to-rat heart and liver xenotransplantation with FK506 plus antiproliferative drugs.

Heterotopic hamster hearts transplanted to unmodified LEW rats underwent humoral rejection in 3 days. Survival was prolonged to a median of 4 days with 2 mg/kg/day FK506. As monotherapy, 15 mg/kg/day cyclophosphamide greatly prolonged graft survival--far more than could be accomplished with RS-61443, brequinar (BQR), mizoribine, methotrexate, or deoxyspergualin. However, when FK506 treatment, which was ineffective alone, was combined with a short induction course (14 or 30 days) of subtherapeutic BQR, RS-61443, or cyclophosphamide, routine survival of heart xenografts was possible for as long as the daily FK506 was continued. In addition, a single large dose of 80 mg/kg cyclophosphamide 10 days preoperatively allowed routine cardiac xenograft survival under FK506. The ability of these antimetabolites to unmask the therapeutic potential of FK506 correlated, although imperfectly, with the prevention of rises of preformed heterospecific cytotoxic antibodies immediately postoperatively. As an adjunct to FK506, azathioprine was of marginal value, whereas mizoribine, methotrexate, and deoxyspergualin (DSPG) were of intermediate efficacy. After orthotopic hepatic xenotransplantation, the perioperative survival of the liver with its well-known resistance to antibodies was less dependent than the heart on the antimetabolite component of the combined drug therapy, but the unsatisfactory results with monotherapy of FK506, BQR, RS-61443, or cyclophosphamide were changed to routine success by combining continuous FK506 with a short course of any of the other drugs. Thus, by breaking down the antibody barrier to xenotransplantation with these so-called antiproliferative drugs, it has been possible with FK506 to transplant heart and liver xenografts with consistent long-term survival of healthy recipients.

Animals↗

Immunopathology of antibodies as effectors of orthotopic liver allograft rejection.

We have come a long way in our understanding of antibodies as effectors of liver graft damage, but we still have much to learn. Animal heterografts provided the first evidence that livers are susceptible to antibody-mediated damage. The pathophysiologic events are similar to those of extrahepatic organ grafts, but the liver is relatively resistant and rapidity of graft destruction is slower, if it occurs at all. Nevertheless, the ABO isoagglutinins can predictably cause human liver allograft failure, often in a quickened, but rarely a hyperacute fashion. The liver is more resistant to lymphocytotoxins, and in many cases will suffer no apparent damage. However, when present, a spectrum of graft pathologic changes can be seen. Early manifestations include hemorrhagic necrosis and lesions mimicking "preservation" injury. Later on, ischemic biliary necrosis and small bile duct loss may be seen. The variability is likely related to a balance between destructive antibody class, specificity, and titers and the ability of the liver to withstand the assault. More precise characterization of lymphocytotoxic antibodies is needed in clinical practice. In addition, antigen distribution in the graft, release of soluble MHC antigens, the role of Kupffer cells and other mechanisms of liver resistance are likely areas of fruitful investigation.

ABO Blood-Group System↗

[Transesophageal atrial stimulation in 168 patients].

Transesophageal atrial stimulation was performed in 168 patients, 95 males and 73 males, 20 to 81 years of age. The indication for atrial stimulation was the study of some bradyarrhythmia in 109 and ischemic heart disease in 59. An esophageal catheter was introduced through the nose and placed at a spot where a bimodal P wave was obtained. Stimulation was performed using a baby Medtronic stimulator coupled to a Vygon amplifier delivering an output of 30 volt. Sinus node recovery time was measured after 2 to 3 min of stimulation at different rates. Wenckebach and 2:1 A-V block as well as ST deviation were determined. Sick sinus syndrome was diagnosed in 41 cases through altered sinus node recovery time and/or secondary pauses; 35 patients showed Wenckebach rhythm at a stimulation rate over 120 per min; 2: 1 A-V block appeared in 22. Ischemic ST-T changes were produced in 20 subjects. No complications were observed, confirming this approach as a simple and effective way to achieve atrial stimulation for diagnostic purposes.

Adult↗

A simple guide for design, use, and evaluation of educational materials.

Few health workers in Latin America are trained in how to produce effective and appropriate health education materials. In order to provide an instrument and a strategy to help overcome this problem, the Pan American Health Organization developed an effective methodology to orient the design, use, and evaluation of health education materials. This article describes the development of this methodology and summarizes the basic operating principles and criteria for evaluation. These operating principles include developing educational materials from the community perspective, ensuring that they are an integral part of a health education program, relating them to health services delivery, pretesting the materials, and distributing instructions for use along with these materials. An evaluation scale helps health personnel assess materials that have been designed elsewhere and decide if they would be appropriate for their own target audiences. The scale also promotes self-evaluation by the community in the development of its own materials. This simple and straightforward methodology has been successfully applied in courses and seminars as well as in the design, use, and evaluation of health education materials throughout Latin America.

Evaluation Studies as Topic↗

[Familial cutaneous leiomyomas and their association with uterine myoma. Study of a 3-generation pedigree].

A review of the classification, localization, symptoms, age of on-set and incidence according to sex of the cutaneous leiomyomas in done. Besides the hereditary aspect and the association of extracutaneous lesions, especially the uterus, are considered. We present the case two sisters affected by multiple cutaneous leiomyoma in association with uterine leiomyoma. Both, members of a family in which the father and 4 of the 8 offsprings present multiple cutaneous leiomyoma, and the daughter of one of the female members (third generation) is also affected of leiomyoma of the uterus. We conclude that the presentation of the leiomyoma in this family is more than a mere coincidence and that there must be some hereditary mechanism, which is interpreted as dominant and the penetrance of the autosomal dominant gene would be about 56%.

Adult↗

[Mycosis fungoides. Clinical study and immunologic response to chemotherapy in 2 cases].

We have presented a study of two cases of Mycosis Fungoides with special emphasis on the staging of the disease as well as on the immunological findings and their modification with chemotherapy. Our objective, to relate the immunological response to clinical evolution, proposes a way of determining prognosis in the evolution of this poorly understood disease.

Adult↗