Biomedical subjects
Publications and source records attributed to I García.
The activity of sparfloxacin on Staphylococcus epidermidis biofilms on different plastic catheters was evaluated. Sparfloxacin showed high bactericidal activity against S. epidermidis biofilms on Vialon and polyvinylchloride catheters. The combination of sparfloxacin with amikacin or rifampicin significantly increased its activity against bacterial biofilms on polyurethane and Teflon catheters.
OBJECTIVE: Donors age 50 years was an exclusion criteria in past decades. The increase of patients in the waiting list has determined the acceptance of older donors (over 65 years old). We analyze our results in liver transplantation using donors over 65 years. PATIENTS: From 1986 to may 1994, we performed 381 OLT. In five cases (1.3%) the OLT was performed using donors over 65 years of age (66, 67, 68, 70 and 71). The selection criteria for donors and recipients were similar to the other transplanted patients. Immunosuppression included cyclosporine or FK-506, prednisone and azathioprine. RESULTS: There were no primary graft failures and preservation damage, biochemical and clinical evolution were not different to the procedures using younger donors. Three grafts presented non-corticoresistant acute rejection. After a follow-up of 11.6 mo (range 4-37 mo) only one graft was lost (Kaposi's sarcoma in the liver). Four grafts and four patients are in excellent biochemical and clinical condition. CONCLUSIONS: Donor age should not be an exclusion criteria. Grafts from older donors (over 65 years old) may be considered safe and will permit to increase the number of OLT.
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Seventy-three patients with Stage III abdominal non-Hodgkin's lymphoma were prospectively treated following two sequential protocols (P): L278 P (group A, 33 patients) (1978-1983) and L384 P (group B, 40 patients), (1984-1991). No patient received radiotherapy. The L278 P included 7 drugs: cyclophosphamide, vincristine (VCR), adriamycin (ADR), prednisone, methotrexate (MTX), dexamethasone, and 6-mercaptopurine, given for remission induction, maintenance, and CNS prophylaxis. In the L384 P we introduced a consolidation phase consisting of intravenous MTX and citrovorum factor rescue, and IV cytosine arabinoside. VCR was also added to the monthly doses and the maintenance phase was reduced from 18 to 15 months. From January 1988 we changed ADR for epirubicin in the same doses. Prophylactic treatment of the CNS, in the L384 P, was intensified by increasing the number of doses of MTX IT in the remission, induction, and consolidation phases, and with the use of ara-C IT. Laparotomy in 50 patients allowed partial resection in 16, and second-look laparotomy was performed in 27 patients. Viable tumor was found in four patients. Three patients (G-A) died from metabolic complications and another 4 (2 G-A and 2 G-B) failed to attain CR and died. A total of 28 (85%) of 33 children of G-A and 38 (95%) of 40 children in G-B achieved CR. Five children died in remission (2 G-A, 3 G-B). Three patients (G-A) relapsed in the CNS and one (G-B) relapsed in the abdomen and died. Disease-free survival at 120 months was 70% in G-A and 84% in G-B.
This is a prospective and nonrandomized study in which 86 children with previously untreated Hodgkin's disease (HD) were clinically staged (CS) and treated with chemotherapy (CT) alone. Fifty-two (CS IA-38, IIA-7, IIB-3, IIIA-4) received six courses of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP). Ten (CS IA with peripheral nodes) received only three courses of CVPP with a reinforcement of C on day 8. Twenty-four (CS IIIB-18, IVA-2, IVB-4) received six courses of CVPP alternating with six courses of epirubicin, bleomycin, and vincristine (EBO). Surgical staging was not performed in any patient. Two patients (CS IIIB) had partial remission and died from progressive disease. Seventy out of 86 children have not relapsed and are in complete remission with a median follow-up of 65 months (range 13-156 months); 14 children relapsed seven to 37 months from diagnosis (median 16 months); one of them (IV B) died of disease. Thirteen are in second and third remission (median 55 months). Actuarial five year survival rates and relapse-free survival rates are 100% and 90% for CS I to IIIA and 81% and 60% for CS IIIB and IV, respectively. As a result of this study, we can conclude that in developing countries most of the children with HD staged by noninvasive diagnostic techniques can be cured with CT alone as primary treatment and thus will not suffer from the late effects of radiotherapy (RT) and the morbidity of laparotomy and splenectomy. RT alone or with other CT combinations should be considered for children who develop relapse of HD.
A cDNA of Trichoderma harzianum (chit42), coding for an endochitinase of 42 kDa, has been cloned using synthetic oligonucleotides corresponding to amino-acid sequences of the purified chitinase. The cDNA codes for a protein of 423 amino acids. Analysis of the N-terminal amino-acid sequence of the chitinase, and comparison with that deduced from the nucleotide sequence, revealed post-translational processing of a putative signal peptide of 22 amino acids and a second peptide of 12 amino acids. The chit42 sequence presents overall similarities with filamentous fungal and bacterial chitinases and to a lesser extent with yeast and plant chitinases. The deduced amino-acid sequence has putative catalytic, phosphorylation and glycosylation domains. Expression of chit42 mRNA is strongly induced by chitin and chitin-containing cell walls and is subjected to catabolite repression. Southern analysis shows that it is present as a single-copy gene in T. harzianum. chit42 is also detected in several tested mycoparasitic and non-mycoparasitic fungal strains.
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The penetration of a new quinolone (BAY Y 3118) into human polymorphonuclear leukocytes (PMNs) was evaluated by a fluorometric assay. The cellular concentration-to-extracellular concentration (C/E) ratio was higher than 6.3 at extracellular concentrations ranging from 2 to 100 mg/liter. The uptake of BAY Y 3118 was rapid, reversible and nonsaturable. The intracellular penetration of BAY Y 3118 was significantly affected by environmental temperature (C/E ratio at 4 degrees C, 5.4 +/- 0.5; control, 7.5 +/- 0.9; P < 0.05) and cell viability (C/E ratio in dead PMNs, 5.5 +/- 0.8; control 7.5 +/- 0.9; P < 0.05), but it was not affected by metabolic inhibitors. The ingestion of opsonized zymosan or opsonized Staphylococcus aureus significantly decreased the levels of PMN-associated BAY Y 3118. Cell stimulation by a membrane activator, however, significantly increased the intracellular concentration of this quinolone. At therapeutic extracellular concentrations (0.5, 2, and 5 mg/liter), BAY Y 3118 showed intracellular activity greater than that of ciprofloxacin against S. aureus in human PMNs. It was concluded that BAY Y 3118 reaches high intracellular concentrations within human PMNs and remains active intracellularly.
Feeding gastrostomy is a method for treating patients unable to ingest food orally. After our experience and good results with the Janeway technique, we decided to perform it by the laparoscopic method. Our first excellent results in seven patients suggest that laparoscopic Janeway gastrostomy is an easy, rapid and efficient surgical technique.
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NGFI-A is an immediate early gene, encoding a zinc finger protein, rapidly activated after mitogenic stimulation. NGFI-A gene expression was found to be rapidly and transiently induced after interleukin-2 (IL-2) stimulation of G1 lymphoblasts, as well as during the G0/G1 transition, when stimulated with concanavalin A (ConA). Activation of both Ca2+ and protein kinase C pathways, separately, in quiescent T lymphocytes produced a partial induction of this gene; however, both stimuli together are necessary to obtain a full response. ConA-induced activation of NGFI-A in quiescent cells was inhibited by immunosuppressors. 8-Bromo-cAMP was able to inhibit the expression of this gene in G1 lymphoblasts after IL-2 stimulation, but failed to interfere with the ConA-induced expression in quiescent T lymphocytes. Exposure of T cells to an NGFI-A antisense oligonucleotide blocked the ConA- and IL-2-induced proliferation of the cells, measured as thymidine incorporation and cell number. This inhibition provides direct evidence that the early gene NGFI-A plays a regulatory role in growth control processes of lymphocytes and that its expression is essential for cellular proliferation.
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A peptide toxin affecting potassium channels was isolated from the sea anemone Bunodosoma granulifera. It facilitates acetylcholine release at avian neuromuscular junctions, competes with dendrotoxin I, a probe for voltage-dependent potassium channels, for binding to synaptosomal membranes of rat brain with a Ki of 0.7 nM and suppresses K+ currents in rat dorsal root ganglion neurones in culture. It represents a new structural type of potassium channel toxin with the sequence V1RCDWFKETA10CRHAKSLGNC20RTSQKYRANC30AKTLQCC37 (M(r) 4275, three disulfides).
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The effect of eight antimicrobial and three antineoplastic drugs on the uptake of fluconazole by human neutrophils and culture epithelial cells was evaluated. Fluconazole reached higher concentrations intracellularly than extracellularly (cellular to extracellular concentration ratio C/E > or = 1.3) in the presence of therapeutical concentrations of the antimicrobial and antineoplastic agents evaluated.
Liver transplantation is a valid treatment in chronic viral B and C hepatitis. But disease recurrence is very frequent in HBV hepatitis after the procedure, and its prevention and treatment are unresolved problems. Hepatitis C recurrence in the graft seems also to be common, and further studies of its pathobiology are needed.
The penetration of fluconazole into human polymorphonuclear leukocytes (PMNs) and tissue culture epithelial cells (McCoy) was evaluated. At different extracellular concentrations (0.5 to 10 mg/liter), fluconazole reached cell-associated concentrations greater than the extracellular ones in either human PMNs (intracellular concentration to extracellular concentration ratio, > or = 2.2) or McCoy cells (intracellular concentration to extracellular concentration ratio, > or = 1.3). The uptake of fluconazole by PMNs was rapid and reversible but was not energy dependent. The intracellular penetration of fluconazole was not affected by environmental pH or temperature. Ingestion of opsonized zymosan and opsonized Candida albicans did not significantly increase the amount of PMN-associated fluconazole. At therapeutic extracellular concentrations, the intracellular activity of fluconazole against C. albicans in PMNs was significantly lower than that of amphotericin B. It was concluded that fluconazole reaches high intracellular concentrations within PMNs but shows moderate activity against intracellular C. albicans in vitro.