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Biomedical subjects

R Cabrera

Publications and source records attributed to R Cabrera.

At least 19 recordsLinked to original sources

[Detection of PNH clones using flow cytometry in aplastic anemia and paroxysmal nocturnal hemoglobinuria].

PURPOSE: To detect and quantify by flow cytometry (FC) PNH clones in paroxysmal nocturnal haemoglobinuria (PNH) and aplastic anaemia (AA) patients. PATIENTS AND METHODS: We have performed a flow cytometric analysis to determine the granulocyte expression of CD55 and CD59 from 29 patients with AA and 11 patients with PNH. RESULTS: In the 11 PNH patients the study showed 58 +/- 34% and 56 +/- 32% (mean +/- SD) CD55(-) y CD59(-) granulocytes. A good correlation was found between the results of FC and haemolysis. The follow-up study showed PNH clone progression in one case and stability in 5 cases. Among 11 AA patients studied at diagnosis, two presented a population of CD55(-) granulocytes (14% and 48%) with CD59 normal, this defect disappeared in both patients after immunosuppressive therapy. The FC study revealed PNH clones in 7 cases among the 26 analyzed after treatment (23 with ATG and/or CyA), in 3 cases with negative Ham's test (in two this became positive 6 and 12 months later). The mean values obtained in these 7 patients with PNH-AA syndrome were 26 +/- 15% y 36 +/- 30% (mean +/- SD) CD55(-) and CD59(-) granulocytes. The median time from diagnosis to detection of PNH phenomenon was 83 months. In the follow-up study, 4 cases had stability, one case had a decrease and one a progression of the abnormal clone. In a retrospective analysis, among the 7 patients with PNH-AA syndrome, 5 had a partial response after the initial treatment. CONCLUSIONS: The FC on granulocytes is a useful method to diagnose and characterize PNH. This test is good for early detection of PNH clones in AA patients at initial diagnosis and in long term survivors. In both diseases it permits measuring the extent of the abnormal clone and its follow up. The extent of the defect is more related to haemolysis than the haematopoietic deficiency. PNH development seems to be more frequent in AA patients with incomplete response after immunosuppressive therapy and in some cases the defect could be latent at the time of diagnosis.

Adult

Antifeedant Delphinium Diterpenoid Alkaloids. Structure-Activity Relationships.

The insect antifeedant and toxic activity of the Delphinium diterpene alkaloids 15-acetylcardiopetamine, cardiopetamine along with its amino alcohol, the beta,gamma unsaturated ketone, and the acetylated ketone derivatives were studied in Spodoptera littoralis and Leptinotarsadecemlineata. Cardiopetamine and 15-acetylcardiopetamine strongly inhibited the feeding activity of S. littoralis and L. decemlineata, respectively. Structure-activity studies with S. littoralis showed that the C13 and C15 hydroxy substituents are essential features of the active molecule, while a C13 hydroxy and/or a C15 acetate determined their effect on L.decemlineata. The C11 benzoate group enhanced the biological effect on both insect species. These alkaloids were not toxic to S. littoralis, while their toxicity on L. decemlineata was inversely correlated with their antifeedant effects, the beta,gamma unsaturated ketone derivative being the most toxic. Cardiopetamine showed little antifungal action against several species of plant pathogens and did not have any mutagenic effects on Salmonella typhimurium by means of the Ames test.

Journal Article

Role of endogenous neurotensin in the behavioral and neuroendocrine effects of cocaine.

The present experiments were designed to assess the role of endogenous neurotensin (NT) in the behavioral response to acute and daily cocaine, after administration of the NT receptor antagonist, SR 48692. Given that glucocorticoids increase the sensitivity to the psychomotor effects of drugs of abuse, we also investigated the effects of SR 48692 on basal and cocaine-induced corticosterone secretion. Acute administration of SR 48692 (1 mg/kg i.p.) reduced the number of rearings induced by cocaine (15 mg/kg i.p.), without modifying horizontal activity. Repeated pretreatment with SR 48692 (1 mg/kg x 5 days) markedly reduced locomotion and rearings after an acute cocaine challenge (day 1), whereas the lower dose of SR 48692 (0.1 mg/kg) had no effect. SR 48692 (1 mg/kg), given daily before cocaine, also decreased cocaine-induced rearing on day 2, but had no effect on the following drug challenges (days 3-10). One week after discontinuing repeated cocaine injections, SR 48692 blocked vertical, but not horizontal, activity induced by an acute cocaine challenge. Rats treated repeatedly with cocaine showed an enhanced behavioral response characterized by the development of stereotypes, which were unaffected by SR 48692. Finally, treatment with SR 48692 did not alter corticosterone circadian secretion nor cocaine-stimulated corticosterone levels, indicating that the attenuation of the behavioral effects of cocaine after NT receptor blockade is not associated with blunted glucocorticoid secretion. These results indicate that administration of SR 48692 attenuates the locomotion and rearing response to cocaine but fails to modify stereotyped behavior, suggesting that SR 48692 modulates the behavioral effects of psychostimulant drugs by acting selectively on the mesolimbic dopaminergic system.

Animals

Pyrrolizidine alkaloids from Heliotropium megalanthum.

Two pyrrolizidine alkaloids, megalanthonine (1) and lycopsamine (2), have been isolated from Heliotropium megalanthum. The structure of the novel compound 1 was determined by spectroscopic methods. The insecticidal, antifeedant, and antifungal effects of compounds 1 and 2 have been evaluated.

Animals

Decreased phosphorylation of GAP-43/B-50 in striatal synaptic plasma membranes after circling motor activity.

The effects of spontaneous circling motor activity on the in vitro phosphorylation of the protein kinase C substrate GAP-43/B-50 was studied on striatal membranes of developing rats (30 days of age). At this time of postnatal development, permanent plastic changes in cholinergic and dopaminergic systems are produced by physiological motor activity. Exercised animals showed a significant reduction of 31% in the level of GAP-43/B-50 endogenous phosphorylation in the contralateral striatum respect to the ipsilateral side (P < 0.01), while control animals did not show asymmetric differences. Compared to controls, the contralateral striatum of exercised animals showed a 33% reduction in the incorporation of 32P-phosphate into GAP-43/B-50 30 minutes post-exercise (P < 0.01). This change in GAP-43/B-50 phosphorylation was correlated with the running speed developed by the animals (r:0.8986, P = 0.015). GAP-43/B-50 immunoblots revealed no changes in the amount of this protein in any group. Moreover, a significant variation of 25% (P < 0.05) in the PKC activity was seen between both exercised striata. Interhemispheric differences were not found in control animals. We conclude that endogenous phosphorylation of this protein is also altered by motor activity in the same period that permanent changes in striatal neuroreceptors are triggered after motor training.

Animals

Rhinocerebral mucormycosis following donor leukocyte infusion: successful treatment with liposomal amphotericin B and surgical debridement.

A 24-year-old male developed cytogenetic relapse of chronic myeloid leukemia (CML) four years after allogeneic BMT. After a year of treatment with IFN-alpha, he achieved a partial cytogenetic response. Treatment with donor leukocyte infusions (DLI) was given (total dose 1 x 10(8) T lymphocytes/kg). Two months later, he developed acute GVHD (skin and liver), that improved with CsA and methylprednisolone and resulted in cytogenetic remission with complete donor chimerism. One month later he developed rhinocerebral mucormycosis and was successfully treated with surgical debridement and liposomal amphotericin B (total dose 12 g). This is the first case of mucormycosis described after DLI.

Adult

Hemostasis and blood requirements in orthotopic liver transplantation with and without high-dose aprotinin.

BACKGROUND AND OBJECTIVE: Several factors seem to lead to considerable bleeding and transfusion requirements during orthotopic liver transplantation (OLT) and postoperatively, but hyperfibrinolysis appears to be the most important factor. Aprotinin, a broad-spectrum serine protease inhibitor, has been shown to inhibit hyperfibrinolytic states. DESIGN AND METHODS: A non-randomized, controlled clinical trial was performed to assess the efficacy of aprotinin in 20 consecutive OLT procedures (group A). The results obtained were compared with the findings in two groups of patients who did not receive aprotinin: one control group (C1) consisting of the 20 consecutive recipients who underwent OLT immediately prior to group A, and a second control group (C2) consisting of the 30 consecutive recipients undergoing OLT immediately after group A. Twenty-three hemostatic parameters were studied in group A and C1 and the blood product requirements were compared in all three group. RESULTS: We observed a markedly reduced fibrinolysis in group A during the non-hepatic and reperfusion phases demonstrated by reduced tissue-type plasminogen activator (t-PA), alpha 2 antiplasmin-plasmin complex (APP) and D dimer levels and an increase in antiplasmin activity compared to C1 group (p < 0.05). In vitro experiments showed aprotinin to have an antiplasmin effect. The intraoperative transfusion of units of RBC and fresh frozen plasma (FFP) was significantly diminished in group A (8.1 and 16.7 U, respectively) when compared with groups C1 (20.4 and 36.0 U) and C2 (13.0 and 28.0 U) (p < 0.05); there was also a significantly greater number of patients not requiring intraoperative platelet transfusion in group A (p < 0.05). During the first 5 postoperative days, the number of patients in group A who did not require RBC transfusion was significantly larger than in groups C1 and C2 (p = 0.04). INTERPRETATION AND CONCLUSIONS: In this study, the inhibition of fibrinolysis associated with the prophylaxis with aprotinin, administered in high doses by continuous intravenous infusion, appears to reduce the need for blood product transfusion during the OLT procedure.

Adolescent

Mucormycosis and hemopoietic transplants.

Mucormycosis is becoming recognized as a serious complication in patients undergoing hemopoietic transplantation (HT), because it is a major cause of morbidity and mortality. In our institution 4 cases of mucormycosis in post-HT period among 345 patients undergoing HT were diagnosed between 1984 and 1997. We studies the clinical characteristics of these cases and we conclude that mucormycosis is not a common infection in patients undergoing HT but that it is followed by a high morbidity and mortality. Maintained neutropenia is the most important risk factor.

Adult

Management of thrombotic microangiopathy following allogeneic transplantation: what is the role of plasma exchange?

Thrombotic microangiopathy (TMA) is an infrequent but serious complication of allogeneic transplantation. The success rate of plasma exchange (PE) reported in the treatment of this entity is a controversial subject. We report the outcome of 10 patients with TMA post-allogeneic transplantation after treatment with PE. Two out of the 10 patients have not responded, five had a partial response, but died of acute GVHD or interstitial pneumonitis, and three have responded and recovered. Our study suggests that there are different degrees of TMA severity. Only mild multifactorial cases with no severe hemolysis (LDH activity <1000 U/l) may be fully resolved with PE.

Adolescent

Epstein-Barr virus associated B-cell lymphoma after autologous bone marrow transplantation for T-cell acute lymphoblastic leukaemia.

Epstein-Barr virus associated lymphoproliferative disease after autologous bone marrow transplantation (ABMT) has rarely been reported. We report a case of B-cell lymphoma following ABMT for T-acute lymphoblastic leukaemia; bone marrow was purged in vitro with monoclonal antibodies to remove T cells. Immunoglobulin and T-cell receptor gene rearrangement studies were used to demonstrate clonality and to show that this patient developed a second neoplasm after ABMT. EBV proteins and genome (type A) were present in post-transplantation lymphoma, suggesting a causative role in its development.

Aged

[Pancreatic pseudocyst. Review of 22 cases].

The management of 22 children with pseudocyst of the pancreas presenting over a 15-year period at three pediatric Hospitals is reviewed. The mean age of patients was 7 years being more common in boys (17:5). Ninety one per cent were due to trauma, while in 9% the cause was unknown. Vomiting (81.8%), abdominal pain (77.2%), a mass (72.7%), fever (31.8%) and anorexia (31.8%) were the most frequent findings. The diagnosis was confirmed by finding hyperamylasemia (elevated in 72.7% of cases), by barium meal and ultrasound. Operative treatment included external drainage in 4 children, cystgastrostomy in 9, cystjejunostomy in 6, and excision in 1. One patient was successfully managed nonoperatively and another had spontaneous gastric drainage. There were no deaths or significative complications in this series.

Abdominal Pain