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Biomedical subjects

A Torres

Publications and source records attributed to A Torres.

At least 343 records · Page 19Linked to original sources

Prediction of recurrence by quantification of p185neu protein in non-small-cell lung cancer tissue.

The concentration of c-erbB-2 oncogene-encoded protein (p185neu) in fresh tumour samples obtained at the time of surgery from 94 non-small-cell lung cancer patients (NSCLC) was determined by an enzyme immunoassay. The relative prognostic importance was estimated, and the influence of other predictors was assessed by means of a Cox's proportional regression model. Median concentration of p185 in tumour tissues was 206 U mg(-1) (range 21-1050 U mg(-1)). p185 level did not differ significantly among subgroups defined by TNM classification, histological type, sex and age. Categorization of patients by p185 level, with 206 U mg(-1) and 343 U mg(-1) taken as cut-off values (corresponding to the 50th and 80th percentiles of the frequency distribution), showed that the recurrence rate, cumulative disease-free likelihood at the 36-month follow-up and median time from surgery to the diagnosis of recurrence worsened progressively as the level of p185 increased. Multivariate analysis confirmed the independent prognostic value of p185 level. Risk of recurrence increased by 1.304 for every increase of 100 units in p185 concentration (95% CI 1.141-1.490) (P<0.001). These findings encourage the inclusion of p185 concentration assay in a future predictive multifactorial prognostic index in NSCLC.

Adult↗

p53 exon 5 mutations as a prognostic indicator of shortened survival in non-small-cell lung cancer.

Inactivation of the tumour-suppressor gene p53 has been described as one of the most common molecular changes found in lung tumours. Our purpose was to study the prognostic value of p53 alterations and to determine whether some specific mutation type in the p53 gene could be associated with poor clinical evolution in non-small-cell lung cancer (NSCLC) patients. To this end, we studied 81 resected primary NSCLCs in order to detect p53 alterations. p53 protein accumulation was analysed using immunohistochemistry methods; p53 gene mutations in exons 5-9 were studied using polymerase chain reaction-single-strand conformation polymorphism and sequencing techniques. p53 protein was immunodetected in 46.9% of lung carcinomas and 44.7% of p53-immunopositive tumours showed p53 mutations. Survival analysis was performed on 62 patients. No survival differences were found for patients with or without p53 immunopositivity. A shorter survival was found in patients with underlying p53 gene mutations, mainly in patients with squamous cell lung tumours; the worst prognosis was found when mutations were located in exon 5 (P = 0.007). In conclusion, the location of p53 mutations might be considered as a prognostic indicator for the evaluation of poor clinical evolution in NSCLC patients.

Carcinoma, Non-Small-Cell Lung↗

Prediction of left ventricular mass changes after renal transplantation by polymorphism of the angiotensin-converting-enzyme gene.

Cardiac complications are the main cause of death in renal transplant patients and left ventricular hypertrophy (LVH) may play a determinant role. An association between the insertion-deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and LVH has been reported in adults. However, little is known about the genetic influence on left ventricular mass changes after renal transplantation, where unique environmental factors, such as cyclosporine A (CsA) and prednisone treatment concur. In fact, CsA treatment has recently been associated with the development of LVH. We prospectively determined the changes on cardiac structure and function, assessed by echocardiographic criteria, in 38 consecutive nondiabetic adults who received a cadaveric renal allograft. They were treated with cyclosporine and prednisone and maintained a good renal function during the follow-up. Echocardiographic studies (M-mode, 2-B and color flow Doppler) were performed without previous knowledge of the genetic typing, at the time of transplantation, and 6 and 12 months later. ACE alleles were typed using a PCR-based assay developed to ascertain the presence of an insertion (I)-deletion (D) polymorphism in intron 16 of the ACE gene. Patients with the so-called "unfavorable" DD genotype (N = 16) were compared with the ID or II genotypes (N = 22). The baseline left ventricular mass index was similar in patients with or without the unfavorable DD genotype (X +/- SE; 166.6 +/- 10.4 vs. 181.3 +/- 9 g/m2, respectively) and a similar proportion fulfilled the criteria of LVH (88% vs. 82%, respectively). The mean percent increase of the left ventricular mass index 12 months after renal transplantation was significantly higher in patients with the DD genotype compared to those with other genotypes (21.3 +/- 7.9 vs. -0.08 +/- 4.9%, respectively; P < 0.05). As a result, 94% of DD patients showed LVH at the end of the follow-up, while 68% of the ID or II patients had LVH (P < 0.05). In addition, the left ventricular ejection fraction significantly increased only in ID or II patients 12 months after transplantation with respect to baseline (ID/II patients, 70.4 +/- 1.5 vs. 63.7 +/- 1.8%; P < 0.05; DD patients, 68.3 +/- 2.1 vs. 63.3 +/- 2.9%). The deleterious effect of the DD genotype was independent of blood pressure, biochemical parameters, weight gain, and cumulative steroids dosages or cyclosporine levels. In conclusion, genetic factors determine the changes on cardiac structure and function after renal transplantation. The presence of the DD genotype of the ACE gene is a marker associated with an elevated risk of LVH in this population.

Adult↗

Lymphokine-activated killer (LAK) cell generation from peripheral blood stem cells by in vitro incubation with low-dose interleukin-2 plus granulocyte-macrophage colony-stimulating factor.

Previous reports have demonstrated granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated enhancement of lymphokine activated killer (LAK) cell function. Based on these studies we have developed a model of LAK cell generation from peripheral blood stem cells (PBSC) from cancer patients by in vitro incubation with low-dose interleukin-2 (IL-2) + GM-CSF. PBSC from seven patients were incubated for 48 h at 37 degrees C in serum-free culture medium supplemented with IL-2 at increasing concentrations (10, 100 or 1000 IU/ml) in the presence or absence of 10 IU/ml GM-CSF. LAK activity generated in cultures with 10 IU/ml IL-2 + GM-CSF was significantly higher than that generated by 10 IU/ml IL-2 and did not differ from LAK generation at optimal concentrations of IL-2 (100 and 1000 IU/ml). PBSC from five additional patients were incubated with low-dose IL-2 + GM-CSF after sequential depletion of the CD4+ and CD8+ T cell subsets. LAK activity was significantly reduced by depletion of both CD4+ and CD8+ T cells and almost completely abolished after depletion of both subsets, suggesting that T cells and not NK cells are the main LAK precursors in this model. Six patients have received two courses of LAK cells generated in vitro by low-dose IL-2 + GM-CSF on day +1 and +8 after PBSC transplant in combination with GM-CSF and IL-2 administration in vivo. The mean LAK activity in peripheral blood of these patients dramatically increased immediately after transplant from a mean of 10% to 43.2% on day +2 and remained increased during the period studied. These results are encouraging and suggest that the administration of in vitro generated LAK cells early after transplant may have a role in the control of minimal residual disease.

Adolescent↗

Absence of detectable PML-RAR alpha fusion transcripts in long-term remission patients after BMT for acute promyelocytic leukemia.

Twenty patients with APL in long-term remission after BMT were analyzed for the presence of the PML-RAR alpha fusion gene by RT-PCR. Ten patients had undergone autologous BMT (six of them peripheral blood stem cell transplantation) and 10 allogeneic BMT. A total of 60 samples were examined by two different protocols. Of the eight patients studied just before conditioning, five showed PML-RAR alpha transcript prior to transplantation. Three of them were in CR and became PCR negative early post-transplantation. The other two patients, that were not in CR before transplant, remained PCR positive, relapsed early post-transplant and died. In the remaining patients no PML-RAR alpha transcripts were visible throughout their post-BMT courses. Our data show that long-term remission after BMT in APL patients is associated with eradication of cells carrying the PML-RAR alpha transcript, and that continued positivity of this test predicts subsequent relapse. The fact of the disappearance of PML-RAR alpha transcript early after BMT in patients previously positive suggest that transplant is capable of curing APL mainly through antileukemic action of the conditioning regimen and therefore, transplantation must be indicated in CR patients if a positive RT-PCR remains after treatment with ATRA plus chemotherapy.

Bone Marrow Transplantation↗

Autologous stem cell transplantation for poor prognosis Hodgkin's disease in first complete remission: a retrospective study from the Spanish GEL-TAMO cooperative group.

Although more than 50% of Hodgkin's disease patients are cured with conventional chemotherapy, many will relapse and eventually die from their disease. Many efforts have been made to identify poor prognostic factors that could be useful in selecting high-risk patients in 1st CR who may benefit from high-dose chemo/radiotherapy. However, the role of early transplantation in 1st CR remains unclear. We have retrospectively analyzed the results obtained with this procedure in 22 hospitals belonging to the Spanish GEL/TAMO cooperative group. Twenty-seven patients, of whom 19 were males, underwent autologous transplantation for Hodgkin's disease in 1st CR between January 1987 and January 1996. Remission had been achieved after one (n = 22) or two (n = 5) lines of treatment. Twenty-four patients had advanced stage disease, 12 patients bulky mediastinal disease, nine bone marrow involvement and 18 had extranodal disease. Peripheral blood was used as the source of hematopoietic stem cells in 15 patients, BM in nine, and both in three. All but three patients received chemotherapy-based conditioning regimens (16 CBV, four BEAM and four BEAC), while three were conditioned with CY and TBI. There were no transplant-related deaths. Median (range) times to recover >0.5 x 10(9)/l neutrophils and >50 x 10(9)/l platelets were 14 (8-56) days and 16 (8-240) days, respectively. With a median follow-up of 30 (8-66) months, 21 patients are alive and in continuous CR. Four patients who relapsed after transplant at 8, 17.5, 22 and 26 months achieved a second CR with conventional chemotherapy; one patient relapsed 92 months post-transplant and died 5 months afterwards. Another patient died 30.5 months post-transplant from a secondary malignancy. In conclusion, high-dose therapy in poor prognosis Hodgkin's disease in 1st CR was well tolerated with no transplant-related mortalities. Although the follow-up of this series is relatively short, our results seem promising. Nevertheless, late relapses can occur, and the role of this procedure vs conventional treatment in very high-risk patients should be assessed in prospective randomized studies.

Adolescent↗

Long-term follow-up of immunosuppressive treatment for obstructive airways disease after allogeneic bone marrow transplantation.

To describe clinical outcome with first line immunosuppression therapy for obstructive airways disease (OAD) after allogeneic BMT, we have retrospectively examined 20 long-term survivors affected by OAD. All patients had normal pulmonary function test (PFTs) before BMT. OAD was defined as FEV1 less than 80%, FER less than 80%, maximum midexpiratory flow rate of 50% vital capacity (MMFR) less than 65%, or residual volume greater than 120. Prednisone (n = 4), CsA (n = 8) and azathioprine (n = 8) have been used as first-line immunosuppression agents. Mean follow-up was 65 months (range 15-142). We identified three categories of patients according to response to treatment: complete (n = 6, 30%), partial (n = 6, 30%) or no response (n = 8, 40%). Age, FEV1, time of onset after BMT, Karnofsky index or immunosuppression modality do not seem to be related to subsequent response. However, patients with low values of MMFR and high values of RV at the beginning of therapy are likely to show poor response. In the complete response group, normalisation of PFTs is achieved within the first months of treatment (median 6 months ranging from 3 to 9 months), suggesting that prolonged therapy is not advantageous and could increase morbidity and mortality if there are no other signs of CGVHD.

Adolescent↗

Myeloperoxidase gene expression in acute lymphoblastic leukaemia.

The FAB classification of acute leukaemias is based on the light microscopic detection of myeloperoxidase (MPO) activity in blast cells. Cases with MPO activity in > or = 3% of blasts are classified as acute myeloid leukaemia. We describe two cases of acute leukaemia in which the blast cells had lymphoid morphology, ultrastructure, immunophenotype and molecular rearrangements, but expressed significant levels of the MPO gene (MPO mRNA) by reverse transcription polymerase chain reaction (RT-PCR), in the absence of translation to protein. Both cases presented a short remission duration. We discuss the incidence, features and outcome of MPO mRNA positive acute lymphoblastic leukaemia (ALL).

Adolescent↗

Quantification of immunocompetent cells in testicular germ cell tumours.

The immunocompetent cells present in the different histological patterns of 43 testicular germ cell tumours were evaluated. CD3 + and CD45RO + (UCHL1 +) T lymphocytes, CD68 + and MAC 387 + macrophages, CD20 + (L26 +) B lymphocytes, and kappa and lambda + plasma cells were counted. The number of immunocompetent cells per mm2 of tumour tissue, excluding the necrotic areas, was evaluated. Microscopic fields were randomly selected by two observers. In order to guarantee randomization each surface was divided into parts, numbered through a lattice, and some fields were chosen via a random numbers table. This procedure yielded significantly different counts from those obtained on subjective selection. The number of T-lymphocytes and macrophages was higher in seminomas than in the non-seminomatous testicular germ cell tumours (P < 0.05) Embryonal carcinomas had more T-lymphocytes than immature teratomas. No significant differences were found among testicular germ cell tumours with regards to the B-lymphocytes, with the exception of the high number of B-lymphocytes in mature teratomas. Kappa + and lambda + plasma cells were few in the testicular germ cell tumours. Randomization in the quantification of immunocompetent cells in testicular germ cell tumours is a good means for evaluation of immune response in all the tumour mass, not only in the areas with the most intense inflammatory cell infiltrate, and permits comparison of testicular germ cell tumours with other malignant tumours. Study of immunocompetent cells in every histological type of testicular germ cell tumour is useful in comparing them with other extra-testicular germ cell tumours.

B-Lymphocytes↗

Occurrence of deoxynivalenol and Fusarium graminearum in Argentinian wheat.

During the 1993 harvest period there was a high incidence of Fusarium head blight in wheat in Argentina. Fusarium species that produce trichothecenes in wheat have been reported in several countries including Argentina. Several studies have shown that F. graminerarum and deoxynivalenol (DON) were the main contaminants detected in wheat and by-products in Argentina. The objective of this study was to evaluate the occurrence of Fusarium spp. and DON contamination in wheat from Córdoba, Argentina during the 1993/94 harvest season. F. graminearum was the main Fusarium species isolated. From 40 samples analysed, 80% showed DON contamination. The levels of DON found ranged between 300 and 4500 micrograms/kg. There was good correlation between F. graminearum and DON contamination. Only five samples showed levels of DON higher than those established in the guidelines in Canada and the USA for food and feedstuffs.

Argentina↗

Outcome of pediatric intensive care at six centers in Mexico and Ecuador.

OBJECTIVE: To improve understanding of the causes of morbidity and mortality among critically ill children in the countries studied. DESIGN: Survey of hospital records between 1992 and 1994. SETTING: Six pediatric intensive care units (ICUs) (four ICUs in Mexico City and two ICUs in Ecuador). PATIENTS: Consecutive patients (n = 1,061) admitted to the units studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mortality rate for low-risk patients (pediatric Risk of Mortality [PRISM] score of < or = 10, n = 701) was more than four times the rate predicted by the PRISM score (8.1% vs. 1.8%, p < .001), with an additional 11.3% of this group incurring major morbidity. The mortality rate for moderate-risk patients (PRISM scores of 11 to 20, n = 232) was more than twice predicted (28% vs. 12%, p < .001). For low-risk patients, death was significantly associated with tracheal intubation, central venous cannulation, pneumonia, age of < 2 months, use of more than two antibiotics, and nonsurgical diagnosis (after controlling for PRISM score). Central venous cannulation and tracheal intubation in the lower-risk groups were performed more commonly in units in Mexico than in one comparison unit in the United States (p < .001). CONCLUSIONS: For six pediatric ICUs in Mexico and Ecuador, mortality was significantly higher than predicted among lower-risk patients. Tracheal intubation, central catheters, pneumonia, sepsis, and nonsurgical status were associated with poor outcome for low-risk groups. We speculate that reducing the use of invasive central catheters and endotracheal intubation for lower-risk patients, coupled with improved infection control, could lower mortality rates in the population studied.

Child, Preschool↗

Long-term functional outcome of inpatient pediatric cardiopulmonary resuscitation.

OBJECTIVE: There is limited information published regarding the long-term outcome of pediatric survivors of inpatient cardiopulmonary resuscitation (CPR). The purpose of this study was to document the long-term (i.e., > or = 1 year after the arrest) functional outcome of children surviving inpatient CPR. METHODS: We reviewed the medical records of children (i.e., less than 18 years of age) receiving advanced CPR (i.e., chest compressions, assisted ventilation, and resuscitation medications) as inpatients in a tertiary care children's hospital. Prospective telephone follow-up of the survivors a minimum of one year after the arrest was performed. A change in the survivors' Pediatric Cerebral Performance Category (PCPC) scale was determined. RESULTS: Approximately half of the 92 subjects were diagnosed with sepsis syndrome. None (0/44) of the patients with sepsis syndrome survived at one year. None (0/24) of the patients who experienced a single episode of advanced CPR > or = 30 min in duration survived one year. Although 36% (33/92) of the patients resuscitated were alive 24 h after their arrest, the proportion surviving fell steadily to 10% (9/92) at one year. Although five of the nine survivors were moderately to severely disabled at one year, the majority (8/9) had little or no change in their PCPC score at one year compared to their prearrest level of function. CONCLUSION: Survival of inpatient pediatric CPR is small. Children surviving inpatient advanced CPR may have little or no change from prearrest function. The survival of hospitalized children with sepsis syndrome requiring CPR or receiving greater than > 30 min of advanced CPR is extremely low.

Adolescent↗

Bronchial mucoepidermoid carcinoma after allogeneic bone marrow transplantation.

A 16 year old man underwent an allogeneic bone marrow transplantation (BMT) from an HLA identical sibling donor for acute lymphoblastic leukaemia in 1984. He developed chronic graft versus host disease involving the skin and kidneys. At day 400 after BMT his condition was complicated by obstructive airways disease, which was partially responsive to azathioprine and steroids. Five years after withdrawal of immunosuppressive treatment he developed dyspnoea and decreased pulmonary function test results, and steroid treatment was resumed. Fibrobronchoscopy revealed the presence of a mucoepidermoid carcinoma in the left main bronchus. After surgical laser resection, there was gradual clinical and functional improvement. There was no evidence of recurrence one year after surgery.

Adolescent↗

Manifestation of circadian rhythm under constant light depends on lighting conditions during lactation.

Adult rats transferred to continuous illumination (LL) show a disruption of circadian rhythms, although the mechanisms underlying this effect are not yet well known. In previous experiments, we found that when rats were born and raised under LL they showed an ultradian pattern during the first 10 days after weaning, but afterward they generated a circadian rhythm that was maintained until adulthood. It was not clear whether this evolution was attributable to the influence of the rhythm of the mother or to the effect of constant light. Here, we have studied the motor activity rhythm of young rats maintained under LL after weaning, taking into account the conditions to which they were exposed during lactation [LL or continuous darkness (DD)]. To check the possible effect of the rhythm of the dam, on the day of delivery some of the dams were blinded, others were subjected to a restricted feeding schedule of 3 h/day, and the others were used as controls. For each rat, the period of the circadian rhythm and the percentage of variance explained by this rhythm were calculated. Results show that all rats maintained under LL during lactation expressed a circadian rhythm in their motor activity. However, rats maintained under DD during lactation did not. This effect did not seem to be dependent on the type of dam. These results suggest that the rhythm of the dams does not affect the manifestation of the rhythm of the pups and that the expression of circadian rhythmicity under constant bright light depends on the lighting conditions under which the animals were maintained during lactation, which could affect the development of the circadian pacemaker or the retina.

Activity Cycles↗

Effects of hypoxia on diaphragm relaxation rate during fatigue.

Skeletal muscle fatigue is associated with a slowing of relaxation rate. Hypoxia may increase the rate at which fatigue occurs, but, surprisingly, mild to moderate hypoxia has not been found to augment the degree of slowing of relaxation during fatigue. The present study tested the hypothesis that severe hypoxia interacts with fatigue in slowing the rate of muscle relaxation and that this can be modulated by altering membranous ionic conductances. Rat diaphragm muscle strips were studied in vitro while aerated with 95% O2-5% CO2 (normoxia) or 95% N2-5% CO2 (hypoxia). During continuous 0.1-Hz stimulation, relaxation rate and force remained stable over time, and relaxation rate was not slowed by hypoxia. Hypoxia accelerated force decline during continuous 5-Hz but not intermittent 20-Hz stimulation. During both 5- and 20-Hz stimulation, relaxation rate became slower over time as force declined, the extent of which was increased significantly by hypoxia. The extent of hypoxia-augmented slowing of relaxation rate during fatigue increased over time and was greater than expected for a given degree of force loss. 4-Aminopyridine did not attenuate or partially attenuated, whereas lowering extracellular Cl-concentration fully attenuated, the hypoxia-induced prolongation of relaxation rate during repetitive stimulation. Thus hypoxia slows relaxation rate to a greater extent than expected for a given degree of force decline, an effect that increases over time, is at most partially attenuated by lowering K+ conductance, and is fully attenuated by lowering membranous Cl-conductance.

4-Aminopyridine↗