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Biomedical subjects

L Larrea

Publications and source records attributed to L Larrea.

33 records · Page 2Linked to original sources

[Invasive fungal infections in patients with blood disorders].

BACKGROUND: Invasive fungal infections (IFI) are severe infectious complications frequently observed in patients with hematological disorders. The aims of this study were to analyse the characteristics of this particular type of infection in a large series of a single institution and to determine the factors associated with the outcome and therapeutic response. PATIENTS AND METHODS: This study reviews the clinical and microbiological features of 155 IFI occurred among 144 patients with hematologic disorders throughout a period of 17 years in a single institution. RESULTS: In 118 cases (82%) the diagnosis was acute leukemia. The main risk factors for developing IFI included a persistent and profound granulocytopenia, the use of broad-spectrum antibacterial agents, indwelling central venous catheters and the damage of normal host barriers following intensive cytotoxic chemotherapy. Candida (65 cases [44%]) and Aspergillus (38 cases [26%]) species were the most common fungal species isolated. An increasing number of IFI were caused by fungi previously considered as contaminants or harmless colonizers. The outcome of IFI was favourable in 78 cases (50%). The most important prognostic factors for the outcome of the IFI were the phase of cytotoxic chemotherapy (p = 0.005), the response of the underlying disease to the cytotoxic chemotherapy (p < 0.00001), and the recovery of neutropenia during the infection course (p < 0.00001). An earlier use of empirical antifungal therapy was also associated with a better outcome. CONCLUSIONS: In spite of earlier treatment and regardless the development of new antifungal agents, the prognosis of IFI in patients with hematological malignancies remains poor. The use of hematopoietic growth factors, through their impact in the duration and severity of neutropenia, may prove valuable the management of IFI in this setting.

Acute Disease↗

[Lymphocyte subsets in blood donors].

OBJECTIVES: To establish the normal values among the different lymphocyte subsets in peripheral blood, measured by surface antigen expression, in healthy population. To observe if there are potential differences in respect of age, gender or sample origin. To compare the absolute lymphocyte number obtained with flow cytometry and with a cellular counter. MATERIAL AND METHODS: Longitudinal and prospective study performed with 100 samples of blood donors. Direct immunofluorescence with triple color staining was made on whole blood, red blood cells were then lysed and samples were analysed with a flow cytometer. The lymphocyte subsets studied were the T lymphocytes and their subsets (CD4 and CD8 lymphocytes), the B lymphocytes and Natural Killer cells population. The absolute lymphocyte count was performed with an automatic cellular counter. Donor data such as age, gender and origin were recorded and were statistically analysed. RESULTS: Normal ranges from the studied parameters are similar to other series. Comparison with gender, origin or age groups gave no significant difference, although there seems to be a tendency to decrease with the ageing of the population. Total absolute lymphocyte number did not differ between the results from the cellular counter or from the flow cytometer. CONCLUSIONS: We found no differences in the absolute lymphocyte number nor in the lymphocyte subsets studied (T lymphocytes, CD4 lymphocytes, CD8 lymphocytes, B lymphocytes and NK cells) with respect to gender, age or sample source. We have established reference ranges for our laboratory. We have not found significant differences in the absolute lymphocyte number measured with cell counter or with flow cytometer.

Adolescent↗

[Monotherapy with meropenem in febrile granulocytopenic patients].

Infection remains the major cause of morbidity and mortality for cancer patients who become granulocytopenic. Combinations of beta-lactams plus aminoglycosides have been the standard empiric therapy for febrile granulocytopenic patients, especially those with profound long-lasting granulocytopenia. The advent of new broad-spectrum cephalosporins and carbapenems has favoured the possibility of empiric monotherapy. Meropenem is a parenteral carbapenem antibiotic stable to renal dehydropeptidase-I which has excellent bactericidal activity against almost all clinically significant aerobic and anaerobic organisms. Meropenem hasta an antibacterial spectrum similar to that of imipenem but it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae, Haemophilus influenzae, Proteus spp, Morganella spp and Providencia spp. Recently, the efficacy, safety, and tolerance of meropenem monotherapy for the empirical treatment of fever in granulocytopenic cancer patients have been compared in two large prospective randomized multicenter trials. The Meropenem Study Group compared monotherapy with meropenem versus ceftazidime and the EORTC conducted a comparative study of meropenem monotherapy versus the combination of ceftazidime plus amikacin. In both groups, success rates were similar by type of infection and infection-related mortality was low. Related adverse events were also similar in both groups. These studies confirm that monotherapy with meropenem is as effective as ceftazidime-containing regimens for the empiric treatment of fever in granulocytopenic patients.

Agranulocytosis↗

[Detection of the PML/RAR alpha rearrangement in acute promyelocytic leukemia using a reverse PCR method].

AIMS: This study describes a molecular method of reverse transcription polymerase chain reaction (RT-PCR) to detect the rearrangement PML/RAR alpha in acute promyelocytic leukaemia (APL) in order to assess its specificity and sensibility, and to evaluate its utility in the characterization of APL patients. PATIENTS AND METHODS: Between January and June of 1995, 64 samples of bone marrow and peripheral blood stem cells (PBSC) cytapheresis were studied. There were 58 APL samples (23 patients: 10 samples obtained with disease activity, 43 samples in complete remission (CR) and 5 PBSC samples) and 6 control samples, of non-APL hematological neoplasms (3 other AML, 1 CML, 1 ALL, and 1 MDS). On the RNA obtained from the isolated mononuclear cells of each sample a conserved region of the PML/RAR alpha fusion gene was amplified by using a RT-PCR with specific primers. RESULTS: The sensitivity assays were performed by diluting PML/RAR alpha positive RNA samples into RNA of controls. The RT-PCR assay was capable to detect the PML/RAR alpha until an 1/1000 dilution in negative control RNA. Nine out of 58 APL samples failed in the amplification of the control gene, and were considered non-evaluable. None of the 6 control samples showed PML/RAR alpha rearrangement. Nine out of 10 APL samples with disease activity were positive for the presence of PML/RAR alpha (the non-positive sample was a non-evaluable one). Six out of 43 APL samples in CR showed the rearrangement, 3 of them corresponding to 2 patients who posteriory relapsed 12 and 19 months after 1st CR. The other 3 positive samples came from other 3 APL patients (24 months in 3rd CR, 14 months in 1st CR and early CR), who remained in CR at the end of the study. No relapse could be noted in patients with negative PCR samples. PML/RAR alpha was not found in any of the 5 APL PBSC samples studied. CONCLUSIONS: The RT-PCR method described here seems to be highly specific as it only detects this rearrangement in LPA patients. Furthermore, the presence of PML/RAR alpha in CR patients could be related to relapse. For all these reasons, this molecular method shows great usefulness and can be advocated, not only for assessing diagnosis, but for as monitoring minimal residual disease in the post remission follow up.

Bone Marrow↗

Autologous bone marrow transplantation for patients with acute myeloblastic leukemia in relapse after autologous blood stem cell transplantation.

Leukemic relapse remains the most frequent reason for treatment failure in patients with acute myeloblastic leukemia (AML) treated with autologous blood stem cell transplantation (ABSCT). The aim of this study was to evaluate the possible role of autologous bone marrow transplant (ABMT) in patients with AML who relapse after ABSCT. Eighteen consecutive patients were enrolled in the study. At ABMT, 17 patients were in untreated relapse and one was in third complete remission (CR). The preparative regimen was BAVC, and consisted of BCNU 800 mg/m2 on day -6, M-AMSA 150 mg/m2/day on days -5 to -3, VP-16 150 mg/m2/day on days -5 to -3 and Ara-C 300 mg/m2/day on days -5 to -3. There were two regimen-related deaths (11%). Thirteen out of 17 patients in untreated relapse before ABMT achieved CR (76%). The cumulative risk of relapse was 58 +/- 13% at 3 years. Seven patients are in CR between 7+ and 53+ months, with a disease-free survival (DFS) probability of 36 +/- 12% at 3 years. The probability of DFS after ABMT was clearly higher in those patients relapsing later than 7 months after the first autograft (52%) than in patients relapsing earlier (20%)(P = 0.02). In a significant proportion of patients, remission duration was clearly longer after ABMT than ABSCT. We conclude that BAVC conditioning followed by ABMT is associated with a low treatment-related toxicity and results in prolonged DFS in a substantial number of AML patients who relapse after ABSCT. Until better therapeutic options become available, ABMT in untreated relapse is a useful alternative in this group of very poor-risk patients.

Acute Disease↗

[Immunohematologic study in 112 patients with myelodysplastic syndromes: 10-year analysis].

PURPOSE: To describe the immunohematological response after multiple red blood cells transfusions in 112 patients with myelodysplastic syndromes (MDS). PATIENTS AND METHODS: From 1982 to 1992 every patient with MDS entered the study. Immunohematological studies consisted of an antibody screening test (AST) and a direct antiglobulin test (DAT) at diagnosis and after every four transfused units of red blood cell concentrates. RESULTS: Twenty-three out of 112 patients (20.5%) presented a positive AST and/or DAT during the study period. Eleven out of the 23 patients (9.8%) developed a positive DAT, six of them with red cell alloantibodies associated. In the remaining 12 patients (10.7%) the immune response observed was the development of red cell alloantibodies without a positive DAT. No patient presented with positive AST or DAT at diagnosis and no differences were observed in the pattern of immunohematological response and the FAB subtype. CONCLUSION: Patients with MDS have disordered immune systems with a high prevalence of autoantibodies against red cells. However, the incidence of red cell alloimmunization is similar to that observed in other multitransfused populations. Finally, despite the high immunization rate, the absence of any hemolytical reaction make the AST and DAT a safe and effective method of pretransfusion testing in this heavily transfused population.

Adolescent↗

Cephalic tetanus studied with single fibre EMG.

In a case of cephalic tetanus with left facial spasms and trismus, the repetitive stimulation of the left facial nerve at 3, 10 and 20 Hz showed no facilitation or decrement. The amplitudes of the blink reflex were 50% lower on the affected side. The silent period of the masseter muscles was shortened. Concentric needle examination of the masseters and left facial EMG of the left frontalis muscle showed increased jitter and blocking in a significant proportion of the recorded potentials. Both jitter and blocking improved on higher innervation rates. All electrophysiological findings were normal on the second examination when the patient was asymptomatic. The single fibre EMG findings point to a presynaptic defect in the neuromuscular transmission in human tetanus.

Diagnosis, Differential↗

Cardiac tamponade and cardiogenic shock as a manifestation of all-trans retinoic acid syndrome: an association not previously reported.

Since the discovery of the differentiating activity of all-trans retinoic acid (ATRA) in acute promyelocytic leukemia (APL), the treatment of this disease has greatly improved. Currently, the combination of ATRA and chemotherapy is considered the best treatment for patients with APL. This approach has consistently extended the remission rate and disease-free survival of APL patients with low mortality. Among ATRA's adverse effects, the retinoic acid syndrome is the most important. It consists of fever, dyspnea, weight gain, pulmonary infiltrates and pleural and cardiac effusions. Other findings occasionally described are lower extremities edema and leukocytosis. We report a case of an retinoic acid syndrome associated with cardiac tamponade due to massive pericardial effusion. This adverse effect, not previously reported, was successfully treated by performing pericardiocentesis followed by the administration of dexamethasone.

Adult↗