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Biomedical subjects

A Alvarez

Publications and source records attributed to A Alvarez.

At least 109 records · Page 6Linked to original sources
PubMed1999

[The autologous transplantation of hematopoietic precursors on an outpatient basis: an analysis of its feasibility at the Hospital Clínic de Barcelona].

BACKGROUND: Autologous stem cell transplantation (ASCT) is increasingly performed on an outpatient basis. Preliminary results show a significant financial saving without modifying the therapeutic results. The aim of this study has been to evaluate the feasibility of this procedure in our the Hospital Clínic of Barcelona, Spain. PATIENTS AND METHODS: All patients in whom an ASCT due to a hematological malignancy, having a good performance status, a caregiver 24 h per day, a lodging near to the hospital and an appropriate cultural and social environment, were offered an outpatient management starting the day after stem cell administration (day +1). RESULTS: During the study period (April, 1997-June, 1998) 64 ASCT were performed. Fifteen patients (23%) were managed on an outpatient basis. The remaining patients were not included in the study due to patient preference (26%), medical reasons (22%), distant home (18%) and social problems (9%). Seven patients (47%) had to be readmitted in the hospital due to fever (n = 4), nausea (n = 2) or respiratory distress (n = 1). Patients receiving total body radiation (TBI) in the conditioning regimen did not have a higher readmission rate than those conditioned without TBI. The median hospital stay (since day +1) was 6 (range: 0-22) and 17 (13-117) days for outpatient and inpatients respectively (p = 0.0016). This reduction would imply a saving of 65% in hospitalization charges and of 12% in total charges. All patients having elected the outpatient management were very satisfied by having made that choice. CONCLUSION: With an appropriate patient selection, outpatient ASCT is a feasible method that may improve the quality of life of the patients and can reduce the costs of the procedure.

Adolescent↗
PubMed1999

Characterisation of the lpdA gene from Neisseria meningitidis by polymerase chain reaction, restriction fragment length polymorphism and sequencing.

P64k protein from Neisseria meningitidis is well recognised in sera from individuals convalescent from meningococcal disease or vaccinated with the Cuban antimeningococcal vaccine VA-MENGOC-BC. The presence of the protein in more than 80 meningococcal strains has also been verified. It is immunogenic in animal models and the antibodies elicited show bactericidal activity against meningococci. To further investigate at the molecular level whether lpdA, the gene coding for P64k protein, is conserved among different N. meningitidis strains, a total of 20 strains isolated from different geographic areas were differentiated on the basis of restriction fragment length polymorphism (RFLP) patterns after polymerase chain reaction (PCR) amplification of the lpdA gene and restriction endonuclease digestion with HpaII. Although a total of five different PCR-RFLP patterns were present, nucleotide sequence determination showed that identity levels were as high as 93-99% among the N. meningitidis strains analysed.

Amino Acid Sequence↗
PubMed1999

[The relationship between the persistence of the BCR/ABL gene and relapse in adult patients with acute lymphoblastic leukemia].

BACKGROUND: The Philadelphia chromosome (Ph') is originated by the t(9;22) which determines the rearrangement BCR/ABL. This rearrangement has been associated with an unfavourable prognosis in patients diagnosed with adult acute lymphoblastic leukaemia (ALL). PATIENTS AND METHODS: The BCR/ABL gene (p210 and p190) was prospectively studied by nested RT-PCR in 17 adult patients diagnosed with ALL BCR/ABL-positive cases were monitored by RT-PCR and cytogenetic techniques over the treatment period (LAL-93 AR protocol). RESULTS: BCR/ABL mRNA was detected in 8 out the 17 patients studied (47%). The Ph' chromosome was detected in 4 cases. Follow-up was completed in 6 out of the 8 BCR/ABL positive cases. PCR only became negative in one patient. The 5 patients with persistently positive BCR/ABL relapsed, whereas the case which became negative was still in complete remission after 24 months follow-up. In 3 out of the 4 Ph' positive patients, the karyotype was normal after induction therapy. CONCLUSIONS: This study clearly demonstrates the usefulness of molecular analysis in the diagnosis and follow-up of ALL compared with conventional cytogenetic techniques. The importance of molecular analysis to assess the efficacy of the treatment used has been emphasized and the poor evolution of BCR/ABL-positive patients has been confirmed.

Adolescent↗
PubMed1999

A prospective, randomized Phase III trial comparing combination chemotherapy with cyclophosphamide, doxorubicin, and 5-fluorouracil with vinorelbine plus doxorubicin in the treatment of advanced breast carcinoma.

BACKGROUND: A prospective, multicenter, randomized, Phase III trial comparing the efficacy of combination chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) with a combination of vinorelbine and doxorubicin (NA) in the treatment of patients with advanced breast carcinoma was undertaken. METHODS: One hundred and seventy-seven patients who previously were untreated for recurrent or metastatic breast carcinoma were entered into the study; 7 patients could not be assessed. The final analysis relates to 85 patients who were treated with FAC and 85 patients who were treated with NA, of whom 21 (25%) and 44 (52%), respectively, had received prior adjuvant chemotherapy. RESULTS: The overall response rates were similar for the two treatments and were unaffected by prior exposure to adjuvant therapy; overall response rate (ORR) for FAC was 74% (95% confidence interval [95% CI], 65-83%), and the ORR for NA was 75% (95% CI, 66-84%). The activity of NA in patients with liver involvement was greater than that of FAC in terms of survival. Overall survivals were similar, with a median of 17.3 months for patients receiving FAC and 17.8 months for patients receiving NA. Severe toxicity was uncommon with World Health Organization Grade 3-4 neutropenia affecting only 7% of patients in each arm of the study. NA was associated with a higher incidence of mild to moderate constipation, neurotoxicity, and phlebitis, whereas FAC produced a slight excess of mild cardiotoxicity. CONCLUSIONS: The efficacy of these two regimens is very similar, although NA may be more active in a subset of patients with visceral metastatic disease, particularly liver involvement. It is clear that, in a direct comparison with an established three-drug regimen, the newer two-drug combination of NA demonstrated equivalent activity with no significant excess of Grade 3-4 toxicity.

Adult↗
PubMed1999

Early visual processing during binocular rivalry studied with visual evoked potentials.

Visual evoked potentials (VEPs) were recorded to probes presented to the dominant and suppressed eyes in a binocular rivalry paradigm. Probes presented to the suppressed eye interrupted the current dominance phase and produced a P300-like deflection (400-700 ms). Probes delivered to the dominant eye increased the duration of the current dominance phase. VEPs to these probes included an endogenous component that overlapped the early exogenous components. The early endogenous component (rivalry-related potential, RRP) started as early as 70 ms and had a broad centroparietooccipital distribution.

Adult↗
PubMed1999

Phase II of doxorubicin/taxol in metastatic breast cancer. Argentine Multicenter Taxol Group.

PURPOSE: To assess the response rate, survival, and toxicity of Taxol (paclitaxel) as 1-h infusion plus doxorubicin as first-line treatment for patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Seventy-six patients with untreated MBC were recruited. All of them had measurable disease and were evaluable for toxicity. Fifty-five percent of the patients had visceral involvement. The dose of doxorubicin was fixed at 50 mg/m2 as a short intravenous infusion, followed by 200 mg/m2 of Taxol as a 1-h intravenous infusion. Doxorubicin was administered during the first seven cycles, continuing with Taxol only up to a maximum of ten cycles. RESULTS: Neutropenia was the most important toxicity: 30% grade 3 and 18% grade 4. Only 2 patients showed a decrease in the left ventricular ejection fraction (LVEF) which caused discontinuing the treatment. No clinical congestive heart failure (CHF) was observed. Seventy-four patients were eligible for response evaluation: 10 (14%) achieved complete response (CR) and 46 (62%) achieved partial response (PR). The mean duration of response was 13.47+/-1.35 months (95% confidence interval (CI): 10.82; 16.12) and the mean survival was 21.50+/-1.42 months (95% CI: 18.72; 24.29). CONCLUSION: The overall response (OR) rate was 76%. No CHF was assessed and 2 patients stopped treatment due to LVEF decrease. Although doxorubicin 50 mg/m2 followed by Taxol 200 mg/m2 in 1-h intravenous infusion presents a toxicity profile which demands a close follow-up, it represents a convenient outpatient schedule with similar activity rate compared to longer Taxol infusions.

Adult↗
PubMed1999

Lack of association of MICA transmembrane region polymorphism and Behçet's disease in Spain.

We have analyzed the distribution of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) transmembrane alleles among 58 Spanish patients with Behçet's disease (BD) and in 194 ethnically matched healthy controls. The study included the characterization of A4, A5, A5.1, A6 "new" and "old" and A9 MICA-TM alleles using polymerase chain reaction. As previously reported, the serological B51 specificity was increased among this BD patient group (36.25% vs. 19.6% in controls; P=0.009; OR=2.33). The MICA-TM alleles A6 ("new" and "old"), in linkage disequilibrium with HLA-B51 and HLA-B14 respectively, were only slightly increased among patients (70.7% vs. 61.3% in controls; P=NS). We conclude that, in contrast to previous finding reporting a strong association of MICA-TM genes and Behçet disease in Japanese patients, in our population HLA-B51 is more closely associated to Behçet susceptibility than MICA-TM genes. Finally, our data show that in Spain, as occurs in other populations, some MICA-TM alleles exhibit strong linkage disequilibrium with certain alleles of the HLA-B locus.

Behcet Syndrome↗
PubMed1999

Nonviral transfer of genes to pig primary keratinocytes. Induction of angiogenesis by composite grafts of modified keratinocytes overexpressing VEGF driven by a keratin promoter.

Cultured epithelial grafts have proven to be life-saving in the treatment of large skin losses. It has become apparent that one of the main difficulties of this technology is the overall poor take of the grafts as a consequence of severely damaged dermal beds. Skin substitutes providing both cultured keratinocytes, as an epidermal layer, and a dermal analogous offer a more suitable material for skin repair. Ex vivo transfer of stroma regeneration-promoting genes to keratinocytes appears to be an attractive strategy for improving the therapeutic action of these grafts. The use of epidermal-specific promoters as expression drivers of exogenous genes results in both high expression levels and stratum specificity, as shown in transgenic mice studies. Most current gene transfer protocols to primary keratinocytes involve transduction of epidermal cells with retroviral vectors. However, transfer of gene constructs harboring these long DNA fragment promoters cannot be achieved through viral transduction. In this paper, we describe a protocol consisting of lipid-mediated transfection, G418 selection and an enhanced green fluorescence protein (EGFP)-based enrichment step for obtaining high levels of transgene-expressing primary keratinocytes. Using this protocol, the cDNA for vascular endothelial growth factor (VEGF), a potent endothelial cell mitogen driven by the 5.2 kb bovine keratin K5 promoter, was stably transfected into pig primary keratinocytes. Genetically modified keratinocytes, expanded on live fibroblast-containing fibrin gels and transplanted to nude mice as a composite material, elicited a strong angiogenic response in the host stroma as determined by fresh tissue examination and CD31 immunostaining. Since the formation of a well-vascularized wound bed is a crucial step for permanent wound closure, the use of an 'angiogenic' composite material may improve wound bed preparation and coverage with cultured keratinocyte grafts.

Animals↗
PubMed1999

Molecular modeling of the amyloid-beta-peptide using the homology to a fragment of triosephosphate isomerase that forms amyloid in vitro.

The main component of the amyloid senile plaques found in Alzheimer's brain is the amyloid-beta-peptide (A beta), a proteolytic product of a membrane precursor protein. Previous structural studies have found different conformations for the A beta peptide depending on the solvent and pH used. In general, they have suggested an alpha-helix conformation at the N-terminal domain and a beta-sheet conformation for the C-terminal domain. The structure of the complete A beta peptide (residues 1-40) solved by NMR has revealed that only helical structure is present in A beta. However, this result cannot explain the large beta-sheet A beta aggregates known to form amyloid under physiological conditions. Therefore, we investigated the structure of A beta by molecular modeling based on extensive homology using the Smith and Waterman algorithm implemented in the MPsrch program (Blitz server). The results showed a mean value of 23% identity with selected sequences. Since these values do not allow a clear homology to be established with a reference structure in order to perform molecular modeling studies, we searched for detailed homology. A 28% identity with an alpha/beta segment of a triosephosphate isomerase (TIM) from Culex tarralis with an unsolved three-dimensional structure was obtained. Then, multiple sequence alignment was performed considering A beta, TIM from C.tarralis and another five TIM sequences with known three-dimensional structures. We found a TIM segment with secondary structure elements in agreement with previous experimental data for A beta. Moreover, when a synthetic peptide from this TIM segment was studied in vitro, it was able to aggregate and to form amyloid fibrils, as established by Congo red binding and electron microscopy. The A beta model obtained was optimized by molecular dynamics considering ionizable side chains in order to simulate A beta in a neutral pH environment. We report here the structural implications of this study.

Algorithms↗
PubMed1999

Usefulness of acute phase reactants in the diagnosis of acute infections in HIV-infected children.

BACKGROUND: Children infected with the human immunodeficiency virus (HIV) often have hypergammaglobulinemia, causing elevation of the erythrocyte sedimentation rate (ESR). This study was done to determine whether C-reactive protein (CRP) is a better indicator of acute infection than ESR in HIV-infected children. METHODS: Erythrocyte sedimentation rate, CRP, and immunoglobulin G (IgG) levels were measured in sick and otherwise healthy HIV-infected children. McNemar's test was used to compare ESR and CRP. RESULTS: In 22 of the 26 cases (85%), the IgG level was elevated, and in all cases ESR was elevated. In 20 of these 22 (91%), both ESR and CRP were elevated. Of the 18 controls, 17 (94%) had elevated IgG, 14 of 17 (82%) had elevated ESR, and 1 (7%) had elevated CRP. The sensitivity for ESR and CRP was 96% and 92%, respectively, and the specificity for ESR and CRP was 17% and 94%, respectively. CONCLUSIONS: Since CRP is more specific than ESR in predicting acute infection in HIV-infected children, it should be used in the evaluation of acute infection in this population.

AIDS-Related Opportunistic Infections↗
PubMed1999

Intravascular and diffuse dermal reactive angioendotheliomatosis secondary to iatrogenic arteriovenous fistulas.

Reactive angioendotheliomatosis is a rare benign process that has been mainly described in patients with systemic infections, such as subacute bacterial endocarditis or tuberculosis, and in association with intravascular deposition of cryoproteins. Histopathologically, it is characterized by a proliferation of endothelial cells within vascular lumina resulting in the obliteration of the involved vessels. Another rare variant of reactive angioendotheliomatosis has been described in the lower extremities of patients with severe peripheral vascular atherosclerotic disease. It consists of violaceous and purpuric plaques histopathologically characterized by diffuse proliferation of endothelial cells interstitially arranged between collagen bundles of the reticular dermis. This second variant has been named diffuse dermal reactive angioendotheliomatosis. We report two patients with reactive cutaneous angioendotheliomatosis appearing distally to arteriovenous fistulas used for hemodialysis because of chronic renal failure. The first patient showed intravascular reactive angioendotheliomatosis, while the second one had purpuric plaques that were characterized histopathologically by diffuse dermal angioendotheliomatosis. Both patients showed an arteriovenous "steal" syndrome with distal ischemia, and it is possible that a local increase of vascular endothelial growth factor, as is the case in hypoxia situations, induces the endothelial proliferation. To the best of our knowledge, cutaneous reactive angioendotheliomatosis has not been previously described in association with arteriovenous shunts.

Aged↗
PubMed1999

Cross-reactivity between the rheumatoid arthritis-associated motif EQKRAA and structurally related sequences found in Proteus mirabilis.

Cross-reactivity or molecular mimicry may be one of the underlying mechanisms involved in the etiopathogenesis of rheumatoid arthritis (RA). Antiserum against the RA susceptibility sequence EQKRAA was shown to bind to a similar peptide ESRRAL present in the hemolysin of the gram-negative bacterium Proteus mirabilis, and an anti-ESRRAL serum reacted with EQKRAA. There was no reactivity with either anti-EQKRAA or anti-ESRRAL to a peptide containing the EDERAA sequence which is present in HLA-DRB1*0402, an allele not associated with RA. Furthermore, the EQKRAA and ESRRAL antisera bound to a mouse fibroblast transfectant cell line (Dap.3) expressing HLA-DRB1*0401 but not to DRB1*0402. However, peptide sequences structurally related to the RA susceptibility motif LEIEKDFTTYGEE (P. mirabilis urease), VEIRAEGNRFTY (collagen type II) and DELSPETSPYVKE (collagen type XI) did not bind significantly to cell lines expressing HLA-DRB1*0401 or HLA-DRB1*0402 compared to the control peptide YASGASGASGAS. It is suggested here that molecular mimicry between HLA alleles associated with RA and P. mirabilis may be relevant in the etiopathogenesis of the disease.

Amino Acid Sequence↗
PubMed1999

Epigenetic modulation of differentiation in CE44 teratocarcinoma.

Teratocarcinoma is a mixed germ cell tumor histologically composed of embryonal carcinoma cells and embryonic and extraembryonic tissues. In the present work we have used the CE44 teratocarcinoma, which is a tumor cell line derived from the OTT6050 experimental tumor, to appreciate the influence the microenvironment has on the modulation of tumoral differentiation. For this, we have studied the development of CE44 teratocarcinoma in primary tumors (subcutaneous and intrasplenic) and in experimental metastases (hepatic and pulmonary). CE44 teratocarcinoma shows variations in its capacity for differentiation in so far as development is concerned and, in hepatic metastases, we noticed a reparative process of the intratumoral necrotic areas which in the same cases were substituted by loose connective tissue. Our results clearly suggest that the microenvironment is decisive in the biological behaviour of the teratocarcinoma cells and that epigenetic factors influence the capacity for differentiation of the undifferentiated tumoral cells.

Animals↗
PubMed1999

Regulatory roles of microtubule-associated proteins in neuronal morphogenesis. Involvement of the extracellular matrix.

As a result of recent investigations, the cytoskeleton can be viewed as a cytoplasmic system of interconnected filaments with three major integrative levels: self-assembling macromolecules, filamentous polymers, e.g., microtubules, intermediate filaments and actin filaments, and supramolecular structures formed by bundles of these filaments or networks resulting from cross-bridges between these major cytoskeletal polymers. The organization of this biological structure appears to be sensitive to fine spatially and temporally dependent regulatory signals. In differentiating neurons, regulation of cytoskeleton organization is particularly relevant, and the microtubule-associated protein (MAP) tau appears to play roles in the extension of large neuritic processes and axons as well as in the stabilization of microtubular polymers along these processes. Within this context, tau is directly involved in defining neuronal polarity as well as in the generation of neuronal growth cones. There is increasing evidence that elements of the extracellular matrix contribute to the control of cytoskeleton organization in differentiating neurons, and that these regulations could be mediated by changes in MAP activity. In this brief review, we discuss the possible roles of tau in mediating the effects of extracellular matrix components on the internal cytoskeletal arrays and its organization in growing neurons.

Cytoskeletal Proteins↗
PubMed1999

[Valoration of the epidermal growth factor receptor (EGFR) in benign breast disease and its relation with expression in malignant tumors classified by hormonal dependence].

The aim of this work is studying the behaviour of EGFR in benign breast pathologies and correlating it to its expression in CDI with hormonal dependency or independency using a radioligand technique. The EGFR expression was higher in FAD rather than in MFQ (mean +/- S.D.: 13.7 +/- 13.5; range: 1.0-55.3; median: 10.0 fmol/mg prot vs mean +/- S.D.: 4.0 +/- 3.5; range:1.0-11.4; median: 2.2 fmol/mg prot), with a result of a positive correlation in the first ones with RP (r = 0.4557) but not with RE. FAD present similar EGFR concentrations to those in CDI-hormonal independents (mean +/- S.D.: 10.7 +/- 12.6; range: 1.0-60.2; median: 6.75 fmol/mg prot), even though the way they are correlated with the content in RP leads us to the conclusion that they are both involved in the genesis and controled development of themselves. On the other hand, MFQ have got similar contents in EGFR to those of CDI hormono-dependents (mean +/- S.D.: 6.98 +/- 15.72; range: 1.0-118; median: 2.55 fmol/mg prot); this fact proves that the development of this pathology does not only depend on the growth factors but also on the hormonal environment which influences it.

Adolescent↗
PubMed1999

[Prevalence of Factor V Leiden and the G20210A mutation of the prothrombin gene in a random group of patients with thrombotic episodes].

UNLABELLED: Factor V Leiden and G20210A mutation of the prothrombin gene have been described as risk factors in thrombophilic pathologies. Our objective has been to know the prevalence of these two mutations in a group of patients with thrombophilic pathology and to compare it with its prevalence in a control group of Spanish population. PATIENTS AND METHODS: 64 patients were divided in two groups. First, 39 patients with deep venous thrombosis (DVT): 24 with an unique episode of DVT; 11 with more than one episode; 3 with DVT and pulmonary thromboembolism, and one with DVT and more than one episode of cerebral thrombosis. Second, 25 patients with other pathologies, such as pulmonary thromboembolism (9 patients), acute cerebrovascular accident (10 patients) and 6 who came to our Department because there were some carrier in their families. The 20210A allele was analyzed in 37 of the 64 patients. Some of the 64 patients had haematological determinations of the activated protein C resistance (APC resistance). As well, 103 unrelated subjects with unknown thrombotic pathologies were analyzed. RESULTS: We have found a prevalence of factor V Leiden in the group of patients of 14.1% (9 carriers in 64 patients, all of them in the first group of 39 patients with DVT) versus 1% in the control group (1 carrier in 103 controls). On the other hand, the difference between the prevalence of the 20210A allele was not statistically significant between the group of patients and the control group (2.7% vs 2.9%). In 75% of the patients no haematological results of APC resistance were obtained, generally because they were with anticoagulant treatment, and in 11.1% of the carriers the result of the determination was considered as ambiguous or false negative. CONCLUSION: Factor V Leiden is well established as risk factor in the thrombophilic pathology, but more studies are needed to know the meaning of the G20210A mutation of the prothrombin gene.

Alleles↗
PubMed1999

[Self monitoring of capillary blood glucose. Evaluation of long-term results (3 to 7 years)].

We analyzed data provided by 60 diabetic patients (DP) included in a Program (P) of Self Blood Glucose Monitoring (SBGM) which showed an initial adherence of at least 6 months. Total follow-up was 67,293 DP-days (110,504 capillary glycemias). Only 50% of DP's remained for > 3 years. Rates of drop-out (DO) peaked early (3th semester (S) and late (10th. S) mean +/- SE of daily SBGM reported in the preprogram period and during the 1st S on P-SBGM by the future DO was significantly higher (4.25 +/- 0.22) than those reported by their P-SBGM-mates who stayed in the program (3.11 +/- 0.29; p < 0.01). DO showed a higher % of capillary glycemias < 60 mg/dl (hypoglycemia) (5.34 +/- 1.49 vs 2.85 +/- 1.14; p < 0.01). During the 3rd S early DO showed significantly higher Glycosilated Hemoglobin (HbA1) levels (10.4 +/- 0.49%) than late DO (8.19 +/- 0.45%; p < 0.01). HbA1's recorded by the late DO's just before leaving P-SBGM were significantly higher (10.14 +/- 0.61%) than those seen at 2nd/5th S (8.2 +/- 0.2; p < 0.01). However, HbA1's of 1-DO at time of abandoning P-SBGM were comparable to those shown by those DP's who remained (10.14 +/- 0.61 vs 9.46 +/- 0.27%). DP's performed daily SBGM's in 70% of possible days during 4 years and in only 50% afterwards. Daily SBGM's was 3.3 +/- 1 during the first 3 years and 2.1 +/- 0.8 thereafter. Compared to preprogram period, all DP's improved HbA1's (12.5 +/- 0.31 vs 9.46 +/- 0.27; p < 0.001) and mean blood glucose (166 +/- 5.2 vs 146 +/- 3.6; p < 0.01). DP's who reached a faster and more satisfactory degree of glycemic control in earlier stages of P-SBGM showed the highest rates of drop-out. Early identification of such patients, as well as setting of feasable and individualy adjusted goals of glycemic control may improve current compliance of DP's on long term tight control.

Adolescent↗