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Biomedical subjects

R Amador

Publications and source records attributed to R Amador.

18 recordsLinked to original sources

Seroprevalence of Trypanosoma evansi in dromedaries (Camelus dromedarius) from the Canary Islands (Spain) using an antibody Ab-ELISA.

After the description in Grand Canary Island of a case of dromedary trypanosomosis caused by Trypanosoma evansi in 1998, an indirect enzyme immunoassay for the detection of specific anti-T. evansi IgG (Ab-ELISA) was used to assess the seroprevalence of this disease on the Canary Islands. Seroprevalence was 9.0% in the four studied islands (Gran Canaria, Tenerife, Lanzarote and Fuerteventura), varying from 10.0 to 7.5% by island (not significantly different). Prevalence using Ab-ELISA was higher than that observed when a parasitological method (microscopic observation of blood smears) was used (1.3%).

Animals↗

Malaria vaccines.

Significant progress has been made in the development of the malaria vaccine during the last 20 years. Ninety percent of the 300-500 million clinical cases of malaria per year worldwide occur in Africa. Thus, research must be directed toward the 1 million African children under 5 years of age who die every year of malaria. An asexual blood-stage vaccine, capable of reducing severe and complicated malaria and malaria-related mortality, is therefore an important public health tool in these countries. Although knowledge of the parasite's biology is incomplete, research has allowed insight into some of the mechanisms that the parasite uses to evade host immunity. This is the basis for adopting an "antigenic cocktail" approach toward obtaining a synthetic or recombinant subunit vaccine such as the synthetic Colombian Malaria vaccine SPf 66. During the development of Spf66, field trials under both low and high malaria endemicity areas in Latin America and Africa have been carried out. The results from these studies showed a protective efficacy ranging between 38.8 and 60.2% against Plasmodium falciparum malaria. Given the characteristics of the normal immune response to malaria (relatively short-lived and not completely effective), it is understandable that the main goal is to try to increase the host's natural immunity. The best candidates for designing a malaria vaccine are the proteins required for parasite survival, those with low mutation rates and conserved epitopes. Because these proteins play an important role in multiple or alternative steps during the invasion process, they should be the targets against which a protective immune response should be elicited. The interaction between the malaria parasite and its host is complex. It is therefore crucial to define new ways of improving the immune response-such as directly modifying the chemical structure of epitopes or using new adjuvants or DNA immunization techniques-to produce novel vaccines against this disease.

Animals↗

Evaluation of SPf66 malaria vaccine during a 22-month follow-up field trial in the Pacific coast of Colombia.

A double-blind randomized placebo-controlled field trial with the SPf66 malaria vaccine was carried out in an endemic area consisting of 14 small villages with exclusive fluvial access, in a rain forest area along the Rosario River, Colombia. A total of 1257 subjects completed the full three dose vaccination schedule on days 0, 30 and 180 (643 vaccinated group/623 placebo group) and were followed-up by passive and active surveillance over a period of 22 months. One hundred and thirty-four Plasmodium falciparum malaria episodes were detected (53 in vaccinated group/81 in placebo group), yielding an attack rate of 5.47 cases/100 person years of follow-up (pyears) in the vaccine group and 8.44/100 pyears in the placebo group. The estimated vaccine protective efficacy was 35.2% (95% CI 8.4-54.2%, P = 0.01). This result supports earlier findings that the SPf66 malaria vaccine diminishes the risk of infection by P. falciparum in endemic areas of South America.

Adolescent↗

Isolated coronary artery transplantation in pigs: a new model to study transplantation arteriosclerosis and humoral rejection.

BACKGROUND: Graft atherosclerosis is a major cause of death after heart transplantation; its causes are multifactorial and poorly understood. To determine whether specific sensitization to coronary artery antigens is a contributing factor, we developed an isolated coronary artery allotransplantation model in pigs. METHODS: Of 46 Yucatan minipigs, 32 received a segment from a farm pig coronary artery into the common carotid artery (coronary allograft group) and 14 had a left to right common carotid artery autotransplant (carotid autograft group). No immunosuppressive drugs were given; all pigs received heparin for 5 days. We examined patency rates, histologic changes, and endothelial deposition of immunoglobulin G and M. RESULTS: In the coronary allograft group, patency rates were 100% (11 of 11) at 1 to 29 days, 20% (2 of 10) at 30 to 89 days, and 0% (0 of 11) after 90 days (overall 40.6%, 13 of 32). Histologic findings included endothelial cell hyperplasia, intimal proliferation, medial necrosis, adventitial inflammation, and ultimately luminal thrombosis. Deposition of immunoglobulin G and M was examined in the patent grafts and was seen in 90.9% (10 of 11) of grafts from days 1 to 29 and in the two patent but partially occluded grafts at 41 and 56 days. All carotid autografts except one (92.8%, 13 of 14) were patent up to 140 days and showed no or mild focal intimal thickening with normal media and adventitia. Deposition of immunoglobulin could not be detected in the autograft group. CONCLUSIONS: In this pig model of coronary artery allotransplantation, typical histologic findings of graft atherosclerosis are produced. Deposition of immunoglobulin G and M occurs early and is associated with endothelial cell hyperplasia and intimal proliferation. This model may be useful for the study of graft atherosclerosis and assessment of interventions designed to halt its progression.

Animals↗

Comparison of performance from three continents on the WHO-Recommended Neurobehavioral Core Test Battery.

To address the need for standardized test batteries, an expert group convened by the World Health Organization (WHO) and the U.S. National Institute for Occupational Safety and Health during 1983 proposed the Neurobehavioral Core Test Battery (NCTB) to identify nervous system effects of chemical exposures in human populations worldwide. To determine the feasibility of using the NCTB in varied cultures, a cross-cultural assessment was conducted under WHO auspices. Data were collected in 10 countries of Europe, North and Central America, and Asia from over 2300 males and females who were not exposed to chemicals at work, within five age ranges between 16 and 65. Results suggest that performance on two NCTB tests (Simple Reaction Time, Benton Visual Retention) is very similar in a broad range of countries and that performance on four other NCTB tests (Santa Ana, Digit Symbol, Digit Span, Aiming) is relatively more variable from country to country, in both males and females. However, data collected from very poorly educated males in one country revealed very low performance levels suggesting that the NCTB may not provide an adequate reference group for identifying (behavioral) neurotoxic effects in such populations. More research is thus needed on evaluating neurotoxicity in poorly educated subjects.

Adult↗

Study of the safety and immunogenicity of the synthetic malaria SPf66 vaccine in children aged 1-14 years.

Safety and immunogenicity tests of the SPf66 malaria vaccine have been carried out on a population of children, aged 1 to 14 years, in the town of Tumaco, Colombia. Adverse reactions measured after each vaccination were local and minimal, and observed in only a small percentage of the vaccinated children. One year later, no delayed reaction was evident. The majority of the child population developed high antibody titres against SPf66 and the degree of response did not vary with age. These induced antibodies recognize the native parasite proteins, in particular the molecules from which the amino acid sequence of this vaccine was deduced. These studies demonstrate that the SPf66 vaccine is safe and highly immunogenic for use in children greater than 1 year old.

Adolescent↗

The first field trials of the chemically synthesized malaria vaccine SPf66: safety, immunogenicity and protectivity.

This paper reports the results of the first field study performed to assess the safety, immunogenicity and protectivity of the synthetic malaria vaccine SPf66 directed against the asexual blood stages of Plasmodium falciparum. Clinical and laboratory tests were performed on all volunteers prior to and after each immunization, demonstrating that no detectable alteration was induced by the immunization process. The vaccines were grouped as high, intermediate or low responders according to their antibody titres directed against the SPf66 molecule. Two of the 185 (1.08%) SPf66-vaccinated and nine of the 214 (4.20%) placebo-vaccinated volunteers developed P. falciparum malaria. The efficacy of the vaccine was calculated as 82.3% against P. falciparum and 60.6% against Plasmodium vivax.

Amino Acid Sequence↗

Safety and immunogenicity of the synthetic malaria vaccine SPf66 in a large field trial.

In the first field trial with synthetic malaria vaccine SPf66 in a large population naturally exposed to malaria, 9957 persons greater than 1 year old and residing on the Colombian Pacific coast received three doses of the vaccine. To evaluate vaccine safety, clinical observations were made 30 min and 48 h after each immunization. There were no adverse reactions in 95.7% of cases. In the 4.3% of cases with adverse reactions, local induration and erythema were the most frequent. In a randomly selected group of vaccinees, anti-SPf66 antibody titers were measured after the third dose: 93% of the vaccinees raised antibodies to SPf66. Among these, 55% had titers greater than 1:1600. These results demonstrate the safety and immunogenicity of the SPf66 vaccine in a large field trial.

Adolescent↗

Determination of the immunization schedule for field trials with the synthetic malaria vaccine SPf 66.

The synthetic malaria vaccine SPf 66 has been shown to be safe, immunogenic and effective in trials performed with controlled groups naturally and experimentally exposed to the disease. In order to continue the trials in open populations, it was necessary to standardize the vaccination characteristics. We have performed four field trials with soldier volunteers with the aim, among others, of defining the number of doses required, the intervals between applications, the protein concentration, and the adjuvant to be used. In these trials, the vaccinated individuals' immune responses were evaluated by assaying anti-SPf 66 antibody titres, in vitro growth inhibition of the P. falciparum parasite, and the vaccinees' capacity to recognize P. falciparum native proteins. From these results we conclude that the best vaccination schedule, for adults, is three doses administered subcutaneously on days 0, 30 and 180, each containing 2 mg of the synthetic polymerized petide SPf 66 adsorbed to alum hydroxide.

Adjuvants, Immunologic↗

Genetic control of the immune response to a synthetic vaccine against Plasmodium falciparum.

Two independent vaccination trials using a hybrid synthetic polypeptide containing epitopes from four proteins of Plasmodium falciparum were performed. In the first trial 63 and in the second 122 volunteers were vaccinated, using different immunization schedules. The analysis of the humoral response to the vaccine, measured by IgG antibody titres to the polypeptide showed a bimodal distribution in both cases suggesting genetic control of the immune response to this protein. There was a small group of low or non-responders and a large group of good responders. HLA phenotyping of the two groups disclosed an association of the low responders to HLA-DR4 antigens with chi-square P value of 0.00039 when compared with the good responders group. These findings provide evidence for the genetic control of the immune response to the synthetic vaccine by the association of this response with particular alleles of the HLA class II antigens; such findings may lead to an explanation of the mechanism involved in disease susceptibility and need to be used in the design of a totally effective vaccine.

Adolescent↗

MRI demonstration of radiographically occult fractures: what have we been missing?

During the course of MRI examinations of the knee for possible internal derangement, the hip for avascular necrosis, and the shoulder for rotator cuff tears, we have encountered many examples of unsuspected fractures of the tibial plateau, femoral condyles, pelvis, hip and proximal humerus. These fractures were either radiographically inapparent or demonstrated very subtle abnormalities that were missed on prospective interpretation. In addition, a large number of patients have been found to demonstrate evidence of intraosseous trabecular disruption, or edema and hemorrhage of medullary bone, or stress type injuries, all of which are radiographically occult. The clinical significance of these osseous abnormalities varies and is dependent upon the degree of injury. It is believed that an awareness of these osseous abnormalities will improve the accuracy of MRI interpretation, will heighten an appreciation of the subtle radiographic abnormalities that may be present, and will improve patient evaluation and management.

Adult↗

A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria.

We have previously shown that a mixture of three synthetic peptides (83.1, 55.1, 35.1), corresponding to fragments of the relative molecular mass 83,000 (83K), 55K and 35K Plasmodium falciparum merozoite-specific proteins, induces protection in Aotus triviroatus monkeys experimentally infected with P. falciparum. Here we describe two polymeric synthetic hybrid proteins based on these peptides that delay or suppress the development of parasitaemia in immunized human volunteers.

Adult↗

Inhibition of acute experimental allergic encephalomyelitis in mice by colchicine.

Colchicine was found to inhibit the clinical and histopathological manifestations of monophasic experimental allergic encephalomyelitis in mice. For inhibition of actively induced disease, inoculation of colchicine at the time of encephalitogenic challenge was found to be most effective. In adoptive transfer experiments, lymph node cells (LNC) from colchicine treated donors failed to transfer the disease. Additionally, colchicine treatment of recipients receiving an otherwise disease-inducing level of sensitized LNC prevented the development of disease. Experiments involving delayed-type hypersensitivity expression support an inhibitory role for the drug on event(s) of the efferent pathway of the cellular immune response.

Animals↗

Observations in a preliminary open trial of estradiol therapy for senile dementia-Alzheimer's type.

Previous studies have suggested that estrogen may have an effect on cognitive and emotional function in women. Studies in rodents and non-human primates have demonstrated the presence of estrogen receptors in brain, and that estrogen can affect behavior in animals. Estrogen administration to ovariectomized rats increases choline acetyltransferase activity in certain regions of brain. Choline acetyltransferase activity is known to be significantly decreased in senile dementia-Alzheimer's type (SDAT). Based on these observations, we treated seven women with SDAT with low dosages of estradiol over a six week period. A battery of assessments was performed throughout the study period. Significant improvements in three women were noted on measures of attention, orientation, mood and social interaction. These estrogen-responsive women were characterized by dementia associated with an affective disorder, older age at onset, and evidence of osteoporosis. Side effects of estradiol therapy included withdrawal bleeding in one woman and transient breast tenderness in another. Estradiol therapy thus may benefit some postmenopausal women with SDAT. The occurrence of osteoporosis in the estrogen-responsive group suggests that SDAT in some women may be associated with or related to a systemic estrogen deficiency state. However, considering the potential for serious side effects as a result of estrogen therapy, the current risk to benefit ratio precludes the routine clinical use of estrogen for dementia until careful clinical research trials have been performed.

Aged↗

[Treatment of Ewing's sarcoma with special reference to radiotherapy].

The authors study 31 cases of Ewing's sarcoma. The survival after 5 years in only 25% for the initially localized tumors because lung and bone metastases finally develop in spite of any treatment. Polychemotherapy defers the appearance of metastases and increases the number of survivors. Patients being less than 15 years old offer a worst prognosis. The tumor localization, existence of general symptoms and their duration, and the alterations of the blood picture were not related with significant variations in the evolution of the Ewing's sarcoma in the studied cases. Probably the prophylactic irradiation of the lungs delays the appearance of metastases.

Adolescent↗