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Biomedical subjects

R Castillo

Publications and source records attributed to R Castillo.

At least 235 records · Page 13Linked to original sources

Evaluation of albendazole prodrugs in experimental trichinellosis.

BACKGROUND: Two albendazole (ABZ) prodrugs, N-methoxycarbonyl-N'-[(2-nitro-4-propylthio) phenyl] thiourea (compound 2), and N-methoxycarbonyl-N'-[(2-nitro-5-propylthio) phenyl] thiourea (compound 3) have recently been synthesized. These compounds showed greater solubility than ABZ itself. METHODS: In order to evaluate the biotransformation of compounds 2 and 3 to ABZ and/or ABZ-sulphoxide (ABZ-SO), plasma samples taken from mice treated with the prodrugs were analyzed by HPLC. Also, the anthelmintic activity of compounds 2 and 3 against Trichinella spiralis was evaluated in the mice experimentally infected with the parasite. RESULTS: The presence of ABZ and/or ABZ-SO was demonstrated in plasma samples taken at different time intervals after prodrug administration, although their levels were low compared to those reached in mice treated with ABZ. Additionally, prodrugs 2 and 3 were also detected in these samples. In regard to the anthelmintic activity of ABZ prodrugs, it was shown that compound 3 was more active than compound 2. Additionally, it was as effective as ABZ against T. spiralis pre-adult, adult, and female fecundity. However, compound 3 was not as active as ABZ against the muscle stage of the parasite. CONCLUSIONS: Compound 3 had better anthelmintic activity against T. spiralis than compound 2. The bioconversion of compounds 2 and 3 to ABZ and/or ABZ-SO was demonstrated by HPLC, but they did not reach equivalent concentrations to that of ABZ. Prodrugs 2 and 3 were also present in plasma samples, suggesting that prodrugs were not efficiently reduced in the intestine of mice.

Albendazole↗

Phase III randomized pilot study comparing interferon alpha-2b in combination with radiation therapy versus radiation therapy alone in patients with stage III-B carcinoma of the cervix.

This randomized pilot study was designed to determine whether the addition of interferon alpha-2b to standard radiation therapy offered an advantage in loco-regional control and survival over radiation therapy alone in a homogeneous group of patients with stage IIIB carcinoma of the cervix. Thirty-six patients were treated with a combination of interferon alpha-2b plus radiation therapy, and 38 patients were treated with radiation therapy alone. Patients with evidence of ureteral obstruction were excluded from the study. Evaluation of loco-regional response was determined by pelvic examination, cervical cytology, biopsies and CT scans when indicated. Survival time was measured from initiation of treatment to date of death or last follow-up. Patient characteristics were comparable between both study arms. The objective complete response rate was 67% in the combined therapy group and 55% in the radiation alone group (P = 0.454). With a median follow-up of 17 months for all patients and 31 months for live patients, 50% of the combined group survived vs. 39.5% of the radiation alone group (P = 0.424). We conclude that the addition of interferon alpha-2b to standard radiation therapy did not significantly improve loco-regional response or survival, although such a trend was noted. We encourage the design of a larger randomized study with sufficient power to detect meaningful differences to prove whether the tendency observed in the present investigation holds any promise to improve the outcome of these patients.

Adult↗

Experimental basis for the use of red cell transfusion in the management of anemic-thrombocytopenic patients.

The Baumgartner perfusion technique was used as an experimental model to study the combined influence of red cell (RBC) and platelet counts on the interaction of platelets with the subendothelium. At normal hematocrit and a platelet count of 100,000 per microliter, platelet adhesion and platelet aggregate (PAG) formation on subendothelium were statistically decreased. At lower platelet counts (50,000/microliter), there was an even more marked reduction in the formation of PAGs. The critical role of RBCs was demonstrated in experiments at low hematocrit; the formation of PAGs was impaired in perfusions at 20 percent hematocrit at any platelet count tested. Platelet deposition on subendothelium was almost absent at 50,000 platelets per microliter, suggesting a negative synergistic effect for the association of low hematocrit (20%) with a low platelet count. Perfusion experiments carried out with nonanticoagulated blood drawn directly from anemic patients with mild thrombocytopenia (43,000-58,000 platelets/microliter) before and after RBC transfusion were in agreement with previous experiments that indicated that normalization of both platelet count and hematocrit is required to achieve optimum hemostasis. Our data give experimental support for the transfusional management of patients with anemia and thrombocytopenia.

Anemia↗

Anti-K1 of the IgA class associated with Morganella morganii infection.

An anti-K1 alloantibody developed in a patient infected with Morganella morganii. The serologic behavior and response to dithiothreitol initially suggested that the alloantibody was an IgM. However, flow cytometry and the separation of immunoglobulin classes by serum chromatography revealed that the anti-K1 was constituted solely of IgA. These data suggest that bacteria-induced red cell antibodies might be of the IgA class.

Aged↗

Medial adductor open reduction for congenital dislocation of the hip.

Twenty-two consecutive patients with 26 dislocated hips were evaluated for a mean of 7 years after open reduction through a medial adductor approach. Severin classification of grade I or II and center-edge angles greater than 20 degrees were present in 73% of hips and 88% of patients treated between the ages of 5 and 14 months. Avascular necrosis (AVN) with partial head involvement occurred in 15% of hips and correlated positively with increased age at surgery, but did not preclude a satisfactory Severin classification. Best results were obtained in children treated between the ages of 5 and 14 months.

Child, Preschool↗

Digital image analysis of platelet-extracellular matrix interactions: studies in von Willebrand disease patients and aspirin-treated donors.

We have developed an automated image analysis method which provides en face morphometric evaluation of platelet interactions with coverslips coated with extracellular matrices. This procedure gives also additional information on the intensity of platelet-surface interactions in the same specimens. To standardize the method, anticoagulated human blood was flowed at 800 s-1 during 10 min at 37 degrees C through a parallel perfusion chamber in which extracellular matrix (ECM)-coated coverslips were placed. The sensitivity of the new method was tested in similar studies performed in patients with von Willebrand disease or treated with aspirin (500 mg/day). The extent of platelet deposition on the ECMs was evaluated by both standard and new morphometric procedures. Coverslips were successively embedded in resin and processed for cross-sectional analysis and results were compared with those provided by the new automated procedure. A good correlation was found between results of covered surface obtained by both methods (r = 0.86; p < 0.005). Results from perfusions performed with blood from patients with platelet defects confirmed the correspondence of grey levels in the digitized images with the heights of groups of interacting platelets calculated from cross sections. The new automated method, in only one stage, allows a reliable evaluation of the global interaction of platelets with the ECM and effectively detected qualitative modifications in platelet-platelet interactions in patients with known platelet defects. The method described could be applied to the evaluation of the interactions of platelets with purified components of the subendothelium.

Aspirin↗

Oral correction of essential fatty acid deficiency in cystic fibrosis.

A combination of pancreatic insufficiency and inadequate caloric intake may produce essential fatty acids (EFA) deficiency in patients with cystic fibrosis. Seventy-five percent of the adolescents and young adults with poor weight gain in our clinic were EFA-deficient by total plasma linoleic acid criteria. Twenty of these patients were placed on an oral hyperalimentation regimen containing 230% of calories required for basal energy expenditure, 40% as fat. Forty percent of these (8/20) achieved normal EFA levels on this diet. Eight of the nonresponding patients were given an additional 5% of their caloric intake as linoleic acid monoglyceride. All who maintained caloric intake achieved normal EFA levels. Normalization of EFA levels was associated with a number of clinical benefits including increase in weight and activity and, in five teenage girls, regulation of menses. The 16 control patients who received standard pancrelipase therapy and nutritional supplements remained fatty acid deficient. We conclude that oral hyperalimentation can restore EFA levels in cystic fibrosis patients if adequate calories are available to provide energy needs.

Cystic Fibrosis↗

The diagnostic importance of species specific and cross-reactive components of Taenia solium, Echinococcus granulosus, and Hymenolepis nana.

Sera from patients infected with Taenia solium, Hymenolepis nana and Echinococcus granulosus were tested against homologous and heterologous parasite antigens using an ELISA assay, and a high degree of cross-reactivity was verified. To identify polypeptides responsible for this cross reactivity, the Enzyme Linked Immunoelectro Transfer Blot (EITB) was used. Sera from infected patients with T.solium, H.nana, and E.granulosus were assessed against crude, ammonium sulphate precipitated (TSASP), and lentil-lectin purified antigens of T.solium and crude antigens of H.nana and E.granulosus. Several bands, recognized by sera from patients with T.solium, H.nana, and E.granulosus infections, were common to either two or all three cestodes. Unique reactive bands in H.nana were noted at 49 and 66 K-Da and in E.granulosus at 17-21 K-Da and at 27-32 K-Da. In the crude cysticercosis extract, a specific non glycoprotein band was present at 61-67 K-Da in addiction to specific glycoprotein bands of 50, 42, 24, 21, 18, 14, and 13 K-Da. None of the sera from patients with H.nana or E.granulosus infection cross reacted with these seven glycoprotein bands considered specific for T.solium infection.

Adolescent↗

Field performance of sugarcane (Saccharum sp.) plants derived from cryopreserved calluses.

This study compared the field performance of sugarcane plants originating from three different sources: control, non-cryopreserved embryogenic calluses, cryopreserved embryogenic calluses and macropropagated material of the same commercial hybrid. Several agronomic traits were evaluated on 100 plants per treatment over a 27-month period covering the growth of the stool and of the first ratoon. Significant differences between treatments were observed only during the first six months of field growth of sugarcane stools. Stems produced from in vitro cultured material, irrespective of their cryopreservation status, had a smaller diameter and a shorter height than those produced from macropropagated material. These differences disappeared by 12 months of stool field growth.

Cryopreservation↗

[Effects of parenteral glutamine in patients submitted to bone marrow transplantation].

UNLABELLED: Bone marrow transplantation (BMT) is a therapy used for hematologic malignancies and solid tumors. Associated chemotherapy and radiotherapy to which these patients are submitted induce secondary effects, with a high metabolic stress. Glutamine is considered a conditionally essential amino acid, and has been shown effective in severe catabolic states. The aim of the study was to assess the effect of parenteral nutrition (PN) therapy supplemented with glutamine on duration of nutritional support in a group of patients with BMT. We have also analyzed associated complications, the nutritional status, the clinical course at 6 months, differences as to type of transplantation, and oral ingestion capability. This is a phase IV, randomized, double blind, and parallel clinical trial, done at a single center. The study was performed on 49 patients, 29% male and 71% female patients, with ages between 21-63 years, distributed in 3 diagnostic groups (leukemia, lymphoma, and solid tumors), and admitted to the Hematology Department of our Hospital. Fifty percent of the patients in each group have received PN supplemented with glutamine (0.4 g/kg/day of L-alanine-L-glutamine), and the other 50% have received standard PN. RESULTS: we have not found significant differences nor at the beginning nor at the end of the study between both groups with regards to studied variables. CONCLUSIONS: PN is and effective therapy for maintenance of the nutritional status in patients submitted to a therapy with a, highly catabolic effect such as BMT. Although we have not been able to show the efficacy of glutamine supplementation in this study with the used dose, it does have been effective in other reports.

Adult↗

The role of breast milk in protecting urban Peruvian children against cryptosporidiosis.

To test the hypothesis that breast milk of nursing mothers may afford children protection against cryptosporidiosis, a prospective cohort study was carried out in the young peoples' community of San Juan de Miraflores near Lima, Peru. Mothers and newborn children were sorted into cohort groups based on the mothers' breast milk antibody response to Cryptosporidium sporozoites using an antibody-capture enzyme-linked immunosorbent assay to detect parasite-specific immunoglobulin A. Children were monitored for Cryptosporidium infection using an indirect immunofluorescence assay. Of 211 mothers enrolled in the study, 39 (18.5%) had high breast milk antibody titers, 107 (50.7%) had medium titers, and 65 (30.8%) had low titers. Sixty-one episodes of Cryptosporidium infection were detected in 50 children of these mothers. Eleven (22%) had mothers in the high antibody titer group, 20 (40%) had mothers in the medium titer group, and 19 (38%) had mothers in the low titer group. The prevalence of infection within children of each group was 0.17, 0.19 and 0.38 respectively. There was no significant difference in the prevalence or duration of infection among children of the different groups. The data does not support the notion that there is protection from Cryptosporidium infection afforded children whose mothers have demonstrable breast milk antibodies against the parasite.

Adult↗

Two-stage papain-indirect antiglobulin test and LISS direct agglutination are not appropriate for pretransfusion screening for unexpected antibodies.

BACKGROUND: The screening for unexpected antibodies has proved to be a suitable pretransfusion compatibility method, but controversy still remains regarding the most appropriate serologic techniques to use in such a screening and, in particular, whether or not to use enzyme-based methods. METHODS: Over a period of three years, 27,149 patient sera submitted to pretransfusion testing were screened for unexpected antibodies. Serologic techniques included LISS-direct agglutination (DAG) reading plus indirect antiglobulin test (IAT), and two-stage papain (2SP)-IAT. RESULTS: In all, 592 (2.18%) serum samples yielded a positive result. Further studies of these specimens disclosed 466 alloantibodies in 371 cases, and 221 unwanted positive reactivities. 2SP-IAT and LISS-DAG allowed the detection of 124 alloantibodies missed by LISS-IAT (78 anti-Lewis, 33 anti-E, 7 anti-P1, 2 anti-K1, 2 anti-K3, 1 anti-M, 1 anti-Cw), but were responsible for 81% of the unwanted positive reactivities. CONCLUSIONS: Since most alloantibodies detected only by 2SP-IAT or LISS-DAG were of doubtful clinical significance, and these techniques produced a high number of unwanted positive reactivities, we conclude that 2SP-IAT and LISS-DAG are not appropriate for the pretransfusion screening for unexpected antibodies.

Agglutination Tests↗