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Biomedical subjects

L Campos

Publications and source records attributed to L Campos.

At least 19 recordsLinked to original sources

Neurological disturbances and hyperdynamic shock in a patient with esophagocoloplasty.

A 39-year-old man, with no history of alcohol intake, who had had an esophago-ileo-colo-gastroplasty with ileotransversostomy, developed diplopia, seizures, metabolic acidosis, and cardiac failure and finally refractory hyperdynamic shock. He died 20 h after admission to our intensive care unit from cardiocirculatory collapse. Postmortem results revealed low erythrocyte transketolase activity, which was increased by 22% by in vitro addition of thiamine diphosphate (TDP effect). Cerebral pathology showed the alterations of Wernicke's encephalopathy. We discuss the possible mechanisms of fatal cardiovascular collapse and the unusual presentation of a case without a history of alcoholic intake or clinical malnutrition.

Acidosis

Acute renal failure due to rhabdomyolysis in diabetic patients.

We report a 32-year-old Black man, admitted to the ICU with coma and severe metabolic disturbances due to diabetic ketoacidosis. During the admission, rhabdomyolysis and acute renal failure (ARF) were diagnosed. After metabolic control and gradual decrease of creatine kinase levels, he presented a progressive improvement of renal function. We emphasize nontraumatic rhabdomyolysis as a poorly recognized pathogenetic factor for ARF in diabetic ketoacidosis and suggest that a better understanding of its mechanisms and an early application of protective measures is necessary.

Acute Kidney Injury

Heterogenous expression of CD15 in acute lymphoblastic leukemia: a study of ten anti-CD15 monoclonal antibodies in 158 patients.

Discrepancies in the literature on acute leukemia blast cell immunophenotypes are sometimes related to differences between the epitopes recognized by various monoclonal antibodies (MoAb) in the same cluster of differentiation. CD15 is one example of such a variation. CD15 expression has been reported in 1.6% to 39% of acute lymphoblastic leukemias (ALL). We studied the expression of CD15 using 10 different commercially available anti-CD15 MoAbs and we observed three different expression patterns using anti-CD15 MoAbs by flow cytometry in 158 cases of ALL: Smy15c was found in 70% of B lineage ALLs, Smy15a and FMC-13 in 30 to 40% of cases and all others in less than 9% of B-ALL cases (p < 0.0001). In T lineage ALLs, Smy15c, Smy15a and FMC-10 identified CD15 in 30% of the cases and all others in less than 8% of the cases. Logistic regression revealed that Smy15a, CD34 and CD14 correlated significantly with Smy15c expression. We conclude that CD15 MoAbs have to be chosen carefully when ALL immunophenotype and subsequent studies of prognostic significance are performed particularly in assessing multiphenotypic ALLs.

Adolescent

Expression of BCL-2 proto-oncogene in adult acute lymphoblastic leukemia.

The products of the BCL-2 gene prolong survival of lymphohematopoietic cells by inhibition of programmed cell death. We studied bcl-2 protein expression in a series of 43 adult acute lymphoblastic leukemia (ALL) at diagnosis, using a specific monoclonal antibody and flow cytometry. All samples expressed bcl-2 with a mean percentage of positive cells of 77.9. The level of bcl-2 in positive cells expressed as mean equivalent of soluble fluorescence (MESF) was highly variable ranging from 5 x 10(3) to 552 x 10(3) (mean +/- s.d.: 96.5 +/- 109 x 10(3)). Neither the percentage of positive cells nor bcl-2 MESF levels were correlated with initial characteristics including blood counts, immunological phenotype, or cytogenetics. The survival of leukemic cells maintained in cytokine-free liquid culture was not correlated with bcl-2 expression. However, cells from ALL with higher white blood cell (WBC) counts, with t(9;22) translocation, or expressing myeloid surface antigens exhibited significantly longer survival in this culture system. The outcome after intensive chemotherapy did not differ according to bcl-2 expression. Factors associated with poor outcome included WBC counts, presence of t(9;22) translocation, presence of myeloid antigens and prolonged survival of cultured cells. These results indicate that high levels of bcl-2 are not associated with distinct clinical or biological characteristics in ALL.

Adolescent

[Treatment and outcome of pneumococcal meningitis in adults. Study of a recent series of 70 episodes].

BACKGROUND: Pneumococcal meningitis (PM) is an infection with high morbidity and mortality. The aim of this study was to evaluate the most relevant clinical, epidemiologic and evolutive characteristics of a recent series of adult patients with this disease. METHODS: Over a period of 10 years all the patients with PM diagnosed by isolation of this microorganism in the cerebrospinal fluid (CSF) were evaluated from a clinical, therapeutic and evolutive points of view. The impact of the new therapies in the disease and the variables associated with mortality were analyzed. RESULTS: Seventy episodes of PM were diagnosed, 60% being found in patients over the age of 50 years. The male/female relationship was 2/1. Fifty-three percent of the patients had other underlying diseases. Acute otitis media (AOM) was the source in 34% of the cases, in 11% the patients had a fistula of CSF and in 9% a pneumonia. At the time of diagnosis 74% of the patients had some degree of reduction in the level of consciousness and in 40% of the episodes the presence of neurologic local manifestations were observed. A decrease in sensitivity to penicillin was observed in 33% of the microorganisms isolated. Third generation cephalosporins were used as initial treatment in 57 episodes and penicillin in other 11 episodes. Adjuvant treatment with dexamethasone, mannitol and/or diphenylhydantoin was administered in 54% of the patients. Overall mortality was 23%: the factors associated with an unfavourable evolution were the existence of underlying disease, deep alteration in the level of consciousness at the time of diagnosis, the coexistence of pneumonia and the absence of adjuvant therapy. CONCLUSIONS: Mortality in pneumococcal meningitis is high. The most relevant risk factor is the initial degree of consciousness. Adjuvant therapies probably determine a reduction in the rate of mortality.

Adult

Survival of MHC-deficient mouse heterotopic cardiac allografts.

The immunologic mechanisms involved in the destruction of murine cardiac allografts were evaluated using MHC-deficient mice. Specifically, we examined the survival of immediately vascularized heterotopic adult cardiac grafts deficient in MHC class I, MHC class II, or both MHC class I and II antigens following transplantation to allogeneic hosts. We observed indefinite cardiac graft survival when donors lacked MHC class II or both MHC I and II antigens. In parallel experiments, we studied the survival of cardiac grafts harvested from normal donors in recipients severely depleted of either CD4 (class II-deficient mice) or CD8 (class I-deficient mice) T cells. Graft survival was dramatically prolonged in the absence of CD4 but not CD8 T cells. Collectively, our results demonstrate that the interaction of host CD4 T cells with donor class II antigens is critical to the rejection of murine cardiac grafts.

Animals

Definition of optimal conditions for collection and cryopreservation of umbilical cord hematopoietic cells.

Prior studies have shown that human umbilical cord blood cells can restore hematopoiesis and be used as a source of stem cells for hematopoietic transplantation. We have performed a study of the best conditions of collection and cryopreservation of blood from eight umbilical cords. We compared the influence of cell separation and of delay between collection and cryopreservation on the numbers of nucleated cells and of hematopoietic progenitors recovered before and after cryopreservation. Ficoll separation resulted in the loss of more than 50% of nucleated cells, but also of a significant number of progenitors before freezing. Unseparated cells could be kept at 25 degrees C as long as 24 h before freezing with minimal loss of progenitors before and after freezing and thawing. In contrast, there was a significant decrease in the number of viable cells and progenitors when cells were maintained at 4 degrees C before freezing. Our data show that cord blood banking is feasible with simple collection and cryopreservation procedures.

Blood Banks

IL-3 increases marrow and peripheral erythroid precursors in chronic pure red cell aplasia presenting in childhood.

In most patients with Diamond-Blackfan anaemia (DBA) the addition of IL-3 to in vitro cultures increases the number of erythroid progenitors. However, a small proportion of patients show an erythroid response to in vivo administration of IL-3. We treated two adult patients with corticosteroid-refractory DBA, who had shown a clear in vitro erythroid response to IL-3, with increasing doses of IL-3 (from 2.5 to 10 micrograms/kg/d) by subcutaneous injections for 7 and 9 weeks. Monitoring of marrow and circulating progenitors showed a sustained elevation of BFU-E and CFU-E as well as an increase of other progenitors and CD34+ cells during therapy. However, this effect did not translate into a clear clinical response, although transfusion requirements decreased transiently in one patient. This report shows that a sustained elevation of erythroid progenitors induced by in vivo IL-3 administration may not translate into an increase of mature red cells production in DBA patients.

Adult

Expression of N-CAM (CD56) on acute leukemia cells: relationship with disease characteristics and outcome.

Expression of CD56 was analyzed by indirect immunofluorescence method on bone marrow samples from 94 newly diagnosed patients with acute leukemia (AL), including 59 acute myelogenous leukemias (AML) and 35 acute lymphoblastic leukemias (ALL). CD56 was expressed on 17 +/- 18% (range: 0-72%) of AML cells and 24 +/- 24% (range: 0-98%) of ALL cells, without significant differences between FAB subtypes in AML, nor immunologic subtypes in ALL. Expression of CD56 was not associated with any clinical or biological characteristic at diagnosis, nor with prognosis in AML or ALL. We do not confirm previously described relationships between CD56 expression and initial characteristics and evolution of acute leukemia.

Acute Disease

Expression of VLA molecules on acute leukemia cells: relationship with disease characteristics.

VLA molecules are involved in the adhesion of hematopoietic cells to the bone marrow stroma and play a role in the mediation of cellular interactions and migrations that are potentially important in the biology of acute leukemia (AL). We studied the expression of VLA-2 (CD49b), VLA-4 (CD49d), and VLA-5 (CD49e) by indirect immunofluorescence on leukemic cells from 67 patients with acute myelogenous leukemia (AML) and 40 patients with acute lymphoblastic leukemia (ALL). VLA-2, VLA-4, and VLA-5 were expressed, respectively, on 13 +/- 17%, 33 +/- 29%, and 36 +/- 30% of AML cells with 20, 54 and 61% positive cases and on 22 +/- 27%, 40 +/- 30%, and 39 +/- 29% of ALL cells with 29, 60, and 61% positive cases. Significant difference was neither noted between French-American-British (FAB) subtypes in AML or ALL nor between immunologic subtypes in ALL. There were highly significant correlations between the expression of the three beta 1-integrins tested in both AML and ALL. In AML, expression of both VLA-4 and VLA-5 was associated with that of CD14 (p = 0.003 and p = 0.01, respectively) and CD19 (p = 0.006 and p = 0.009, respectively). Expression of VLA-5 was correlated with that of CD15 (p = 0.004). Expression of VLA-4 was associated with both a high initial blast cell count (p = 0.01) and high percentage of bone marrow blast cell involvement (p = 0.003). In ALL, expression of VLA molecules was correlated neither with differentiation antigen nor with hematologic features. In AML, as in ALL, no significant correlation was noted between expression of VLA molecules and evolution of the disease.

Adult

Immunophenotype of adult acute lymphoblastic leukemia, clinical parameters, and outcome: an analysis of a prospective trial including 562 tested patients (LALA87). French Group on Therapy for Adult Acute Lymphoblastic Leukemia.

The aim of the multicentric trial LALA87 was to test the efficacy of different postremission therapies in adults (15 to 60 year olds) with acute lymphoblastic leukemia (ALL). An immunologic subclassification based on surface marker expression was proposed. Among the 562 tested patients, 511 were assigned either to the B lineage (361 cases, 63%) or to the T lineage (150 cases, 26%). T-ALL were significantly associated with male sex, age less than 35 years, mediastinal mass, central nervous system involvement, high white blood cell count, and low anemia. In a univariate and multivariate analysis, T-cell leukemia had a more favorable outcome than B-cell leukemia with respective median disease-free survivals (DFSs) of 28 and 14 months (P < .005). However, the type of postremission therapy modifies the value of the immunophenotype prognostic factor. In the chemotherapy arm, T-ALL patients (26 patients) had a more favorable outcome than B-ALL patients (57 patients) (P < .003). In the autologous bone marrow transplantation (ABMT) arm, the apparent better outcome of T-ALL patients (35 T/50 B) did not reach statistical significance (P = .2) and there was no difference in the allogeneic bone marrow transplantation (alloBMT) arm (37 T/71 B: P = .9). In the B-cell-lineage leukemias, subclassification by stages and myeloid antigen coexpression (10%) were not associated with different prognosis. CD10+ T-ALL (31 patients) were associated with a better DFS compared with the CD10- T-ALL (73 patients) with respective median DFS, not reached and 18.5 months (P = .04).

Adult

Effects of BCL-2 antisense oligodeoxynucleotides on in vitro proliferation and survival of normal marrow progenitors and leukemic cells.

Previous studies have shown that the BCL-2 protooncogene encodes a mitochondrial protein that promotes cell survival by blocking programmed cell death. Bcl-2 protein has been detected in normal immature myeloid cells and in acute myeloid leukemia (AML) cells. To assess its functional role in normal and leukemic hematopoiesis, we performed serum-free cultures of CD34+ normal marrow cells, of bcl-2-positive myeloid lines, and of AML cells in the presence of bcl-2 sense, nonsense, and antisense phosphorothioate oligodeoxynucleotides. In all antisense-treated cultures, we observed (1) an inhibition of bcl-2 protein expression by day 4 to 6 of culture; (2) a decrease in cell survival duration; and (3) a decrease in the number of clonogenic cells present in the culture. Moreover, exposure to chemotherapeutic drugs resulted in more effective killing of AML cells in the presence of antisense oligomers. We conclude that bcl-2 protein is necessary for the survival of myeloid cells in culture, and that it may be implicated in the resistance of AML cells to chemotherapy.

Base Sequence

The failure of intrathymic transplantation of nonimmunogenic islet allografts to promote induction of donor-specific unresponsiveness.

Freshly isolated allogenic pancreatic islets transplanted into the thymus of transiently immunosuppressed rats are not rejected but survive indefinitely while also inducing a state of specific unresponsiveness that permits survival of secondary donor-strain islets transplanted extrathymically. Since freshly isolated pancreatic islets contain intraislet antigen-presenting cells as well as endocrine cells it is unclear which cellular component is primarily responsible for mediating unresponsiveness. We therefore examined the impact of pretransplant in vitro culture (a maneuver which selectively depletes intraislet APCs) on the capacity of islet allografts to induce unresponsiveness after intrathymic implantation. APC-depleted pancreatic islets, which are known to have reduced immunogenicity, survived indefinitely in the thymus of allogeneic hosts whether or not brief immunosuppression was employed, but failed to promote survival of subsequent donor-strain islets transplanted to an extrathymic site. These findings emphasize the central role of APCs in the induction of transplantation tolerance in this model, and are consistent with the established role of this population in the development of T cell tolerance in the thymus.

Animals