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Biomedical subjects

A Antón

Publications and source records attributed to A Antón.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prognostic impact of bulky mediastinal lymph nodes (N2>2.5 cm) in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) treated with platinum-based induction chemotherapy.

A group of 70 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treated in different phase II-III trials with platinum-based chemotherapy in two institutions, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were patients with stage IIIA (N2)-IIIB, Eastern Cooperative Oncology Group performance status 0.1 and less than 5% weight loss. All 37 patients with stage IIIA(N2) were treated with platinum-based induction chemotherapy followed by surgery plus radiotherapy if no progression was observed. The other 33 patients with stage IIIB were treated with platinum-based induction chemotherapy followed by conventional fractionation radiotherapy if no progression was observed. The overall response rate to induction chemotherapy was 40%. Median survival of the 70 patients was 13 months, with a 4-year survival of 15%. At univariate analysis, two prognostic factors correlated with survival: partial or complete response to induction chemotherapy (P<0.00001) and bulky mediastinal lymph nodes (N2>2.5 cm) (P=0.03). At multivariate analysis, only the response to induction chemotherapy retained statistical significance (P=0.00001). Randomized well-balanced prospective trials considering initially mediastinal N2 node size are needed to clearly establish the role of chemotherapy, surgery and radiotherapy in LA-NSCLC.

Adult↗
PubMed2000

Economic evaluation in a randomized phase III clinical trial comparing gemcitabine/cisplatin and etoposide/cisplatin in non-small cell lung cancer.

INTRODUCTION: Information on the relative cost-effectiveness of treatments for cancer is being increasingly sought as pressure on health care resources increases. The objective of this study was to assess the cost-effectiveness of gemcitabine/cisplatin (GC) versus cisplatin/etoposide (CE) in patients with advanced non-small cell lung cancer (NSCLC), using resource utilization data collected in conjunction with the first randomized clinical trial comparing both combinations. METHODS: Efficacy and medical care resource utilization data were collected prospectively in an open-label, multicenter, randomized, comparative, phase III trial conducted in Spain which compared gemcitabine/cisplatin and cisplatin/etoposide in 135 chemonaive patients with Stage IIIB or IV NSCLC. There were no differences between both regimens when survival was used as primary end-point, so a cost-minimization analysis was used to compare them. In addition, cost-effectiveness analyses were conducted when percentage of responses and time to progression were used as secondary end-points. RESULTS: There were no differences between both regimens when survival was selected as the efficacy end-point. Despite the higher chemotherapy cost of GC when compared to CE, there were no differences in total direct costs (584523 pts for GC and 589630 pts for CE; P=NS) between both regimens. Potential savings with GC were mainly associated with a decrease in hospitalization rate. There were differences in favor of GC when response rate (40.6% for GC and 21.9% for CE; P<0.05) and time to disease progression (8.7 months for GC and 7.2 months for CE; P<0. 05) were used as clinical end-points. GC presented a favorable cost-effectiveness profile when compared to CE. CONCLUSIONS: This prospective economic evaluation conducted alongside a clinical trial offers valuable preliminary information on the potential efficiency of the combination gemcitabine-cisplatin in NSCLC. Future assessments based on larger clinical trials focused on survival and naturalistic economic studies conducted in real clinical practice settings are necessary to confirm these findings.

Aged↗
PubMed2000

Predicting the result of noninvasive ventilation in severe acute exacerbations of patients with chronic airflow limitation.

OBJECTIVE: To analyze prospectively the factors related to the success of noninvasive ventilation (NIV) in the treatment of acute exacerbations of chronic airflow limitation (CAFL) and to generate a multiple regression model in order to detect which patients can be successfully treated by this method. SETTING: A respiratory medicine ward of a referral hospital. METHODS AND PRINCIPAL RESULTS: Initially, we examined 44 episodes of acute respiratory failure in 36 patients with CAFL in whom mechanical ventilation was advisable. In 34 of 44 episodes (77%), NIV was used successfully. Patients in whom NIV succeeded had a lower FEV(1) prior to admission, a higher level of consciousness (LC), and significant improvements in PaCO(2), pH, and LC after 1 h of NIV. A logistic regression model consisting of baseline FEV(1) and PaCO(2) values, initial PaCO(2), pH, and LC values on admission, and PaCO(2) values after 1 h of NIV allowed us to correctly classify > 95% of the 44 episodes in which the outcome was successful. In the second part of the study, we prospectively validated the equation in another 15 consecutive CAFL patients with acute hypercapnic respiratory failure. NIV successfully treated 12 patients (80%), and the model correctly classified 14 patients (93%). CONCLUSION: Good LC at the beginning of NIV and improvements in pH, PaCO(2), and LC values after 1 h of NIV are associated with successful responses to NIV in COPD patients with acute hypercapnic respiratory failure. Our validated multiple regression model confirms that these variables predict the result of NIV in acute hypercapnic failure in CAFL patients.

APACHE↗
PubMed1999

Characterization of the simultaneous binding of Escherichia coli endotoxin to Kupffer and endothelial liver cells by flow cytometry.

BACKGROUND: The triggering of cellular responses during endotoxic shock is initiated for the binding of endotoxin (lipopolysaccharide; LPS) to the cell surface. Kupffer and endothelial liver cells, involved in the removal of endotoxin from blood circulation, show in vitro a rapid response to LPS in the absence of serum. METHODS: A double-labeling fluorescent assay was designed to evaluate the binding properties of Escherichia coli O111:B4 LPS to individual endothelial and Kupffer cells in suspension, where both populations occurred in the same relative proportion as in liver. After immunolabeling of the Kupffer cell population with the monoclonal antibody ED1 conjugated to R. phycoerythrin, the binding characteristics of LPS labeled with fluorescein to both endothelial and Kupffer cells were simultaneously studied by flow cytometry in serum-free conditions. RESULTS: Specific and saturable binding of endotoxin was observed with both populations, showing properties of a receptor-mediated process. The Kupffer cell population showed a faster capacity and a higher affinity for LPS binding. The Hill coefficients indicated positive cooperativity in the LPS interaction with both populations. CONCLUSIONS: Specific endotoxin binding to liver sinusoidal cells occurs in a serum-independent manner, particularly at high LPS concentrations. Flow cytometry is a fast, precise, and efficient technique to evaluate the simultaneous interaction of a ligand with two different cell types.

Animals↗
PubMed1999

Maximal strength and power characteristics in isometric and dynamic actions of the upper and lower extremities in middle-aged and older men.

Muscle cross-sectional area of the quadriceps femoris (CSAQF), maximal isometric strength (handgrip test and unilateral knee extension/flexion), the shape of isometric force-time curves, and power-load curves during concentric and stretch-shortening cycle (SSC) actions with loads ranging from 15 to 70% of one repetition maximum half-squat (1RMHS) and bench-press (1RMBP) were examined in 26 middle-aged men in the 40-year-old (M40) (mean age 42, range 35-46) and 21 elderly men in the 65-year-old age group (M65) (mean age 65, range 60-74). Maximal bilateral concentric (1RMHS and 1RMBP), unilateral knee extension (isometric; MIFKE and concentric; 1RMKE) strength and muscle CSA in M65 were lower (P < 0.001) than in M40. The individual values of the CSAQF correlated with the individual values of maximal concentric 1RMHS, 1RMKE and MIFKE in M65, while the corresponding correlations were lower in M40. The maximal MIFKE value per CSA of 4.54 +/- 0.7 N m cm-2 in M40 was greater (P < 0. 05-0.01) than that of 4.02 +/- 0.7 N m cm-2 recorded in M65. The maximal rate of force development of the knee extensors and flexors in M65 was lower (P < 0.01-0.001) and the heights in squat and counter-movement jumps as much as 27-29% lower (P < 0.001) than those recorded in M40. M65 showed lower (P < 0.001) concentric power values for both upper and lower extremity performances than those recorded for M40. Maximal power output was maximized at the 30-45% loads for the upper extremity and at the 60-70% loads for the lower extremity extensors in both age groups. Muscle activation of the antagonists was significantly higher (P < 0.01-0.001) during the isometric and dynamic knee extension actions in M65 than in M40. The present results support a general concept that parallel declines in muscle mass and maximal strength take place with increasing age, although loss of strength may vary in both lower and upper extremity muscles in relation to the type of action and that ageing may also lead to a decrease in voluntary neural drive to the muscles. Explosive strength and power seem to decrease with increasing age even more than maximal isometric strength in both actions but power was maximized at the 30-45% loads for the upper and at the 60-70% loads for the lower extremity action in both age groups. High antagonist muscle activity may limit the full movement efficiency depending on the type of muscle action, testing conditions and the velocity and/or the time duration of the action, especially in the elderly.

Adult↗
PubMed1999

Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: We conducted a randomized trial to compare gemcitabine-cisplatin with etoposide-cisplatin in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). The primary end point of the comparison was response rate. PATIENTS AND METHODS: A total of 135 chemotherapy-naive patients with advanced NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 intravenously (IV) days 1 and 8 or etoposide 100 mg/m2 IV days 1 to 3 along with cisplatin 100 mg/m2 IV day 1. Both treatments were administered in 21-day cycles. One hundred thirty-three patients were included in the intent-to-treat analysis of response. RESULTS: The response rate (externally validated) for patients given gemcitabine-cisplatin was superior to that for patients given etoposide-cisplatin (40.6% v 21.9%; P = .02). This superior response rate was associated with a significant delay in time to disease progression (6.9 months v 4.3 months; P = .01) without an impairment in quality of life (QOL). There was no statistically significant difference in survival time between both arms (8.7 months for gemcitabine-cisplatin v 7.2 months for etoposide-cisplatin; P = .18). The overall toxicity profile for both combinations of drugs was similar. Nausea and vomiting were reported more frequently in the gemcitabine arm than in the etoposide arm. However, the difference was not significant. Gemcitabine-cisplatin produced less grade 3 alopecia (13% v 51%) and less grade 4 neutropenia (28% v 56% ) but more grade 3 and 4 thrombocytopenia (56% v 13%) than did etoposide-cisplatin. However, there were no thrombocytopenia-related complications in the gemcitabine arm. CONCLUSION: Compared with etoposide-cisplatin, gemcitabine-cisplatin provides a significantly higher response rate and a delay in disease progression without impairing QOL in patients with advanced NSCLC.

Adult↗
PubMed1999

UFT plus or minus calcium folinate for metastatic colorectal cancer in older patients.

Two studies were carried out to determine the activity and evaluate the toxicity of oral chemotherapy with uracil and tegafur in a 4:1 molar ratio (UFT) plus or minus calcium folinate in elderly patients with advanced colorectal cancer. In one study, 106 patients received a fixed dose of UFT 400 mg/day in two daily doses every 12 hours continuously, plus calcium folinate 45 mg/day administered in three divided doses every 8 hours continuously. In study 2, calcium folinate was omitted, and the dose of UFT was increased to 400 mg/m2/day in two daily doses administered every 12 hours continuously to 95 patients. Treatments for both studies were administered until grade 3 or grade 4 toxicity occurred or disease progressed. The response rate among the 96 available patients in study 1 was 17.7% (95% confidence interval [CI], 10% to 27%); 41 patients (43%) achieved an objective response or stable disease. Overall survival was 13.7 months with a statistically significant difference between patients with no progressive disease and patients with progressive disease (P < .01). In study 2, 62 of 95 patients have now been evaluated for response. The response rate was 21% (95% CI, 13% to 30%); 38 patients (61%) experienced an objective response or stable disease. The overall survival for study 2 has not yet been evaluated. Toxicity was generally mild, consisting of grade 3 nausea/vomiting (6% in study 1 and 2% in study 2), grade 3 or grade 4 diarrhea (11% in study 1 and 7% in study 2), plus one case of grade 3 mucositis in study 1. These findings suggest that chemotherapy with UFT (with or without modulation with calcium folinate) is feasible for elderly patients with advanced colorectal carcinoma.

Adenocarcinoma↗
PubMed1999

Our experience with Wallstent self-expanding metal prostheses in 65 patients with malignant dysphagia.

OBJECTIVE: to document the usefulness of self-expanding metal stents in patients with malignant dysphagia. METHOD: from January 1992 to January 1997 we implanted 75 Wallstent prostheses (28 uncovered AV, 20 uncovered Unistep, 15 covered Telestep, and 2 covered double-mesh Permalume stents) in 65 patients with malignant dysphagia. RESULTS: mean survival time was 100 days in patients with uncovered stents, and 215 days in patients with covered stents. Oral feeding was possible throughout the post-implantation course in 58 of 65 patients. Only two severe complications occurred: esophageal perforation with mediastinitis, and migration of the stent from the distal esophagus into the stomach. All implantation procedures were done under radiological guidance. For AV and Unistep prostheses we used a nasal approach without sedation, and for Telestep and Permalume stents we used an oral approach with sedation. CONCLUSIONS: Wallstent self-expanding metal stents are useful in palliating malignant dysphagia. The placement and implantation of these stents are straightforward.

Adult↗
PubMed1998

Phase II trial assessing the combination of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC).

BACKGROUND: There is need for more active and better tolerated combinations in non-small cell lung cancer (NSCLC). The Spanish Lung Cancer Group (SLCG) therefore conducted this phase II study to define the efficacy and toxicity profile of the combination of higher doses than usual of gemcitabine along with cisplatin in patients with advanced NSCLC. PATIENTS AND METHODS: Forty patients with pathologically documented advanced NSCLC were included in this trial (34 men, six women; aged 34-74 years; mean 64 years). Twenty-two patients had unresectable stage IIIB disease and 18 had stage IV disease. Karnofsky performance status was > or =70%. In five patients, surgery had previously been performed and four patients had received radiotherapy. Gemcitabine at a dose of 1200 mg/m2 was administered weekly (days 1, 8 and 15) and cisplatin 100 mg/m2 on day 15 of each 28-day cycle. RESULTS: Responses were scored according to standard World Health Organization criteria. Of 40 assessable patients, 19 had a partial response for an overall response rate of 47.5% (95% confidence interval (CI) 32-64%). To date, median survival for the whole group is 10.4 months (95% CI 6.2-11.7 months), with a 1-year survival rate of 35%. Toxicity was mainly haematological. Seven patients (18%) had grade 4 neutropenia (one episode of febrile neutropenia). Thrombocytopenia (12.8% grade 3 and 2.6% grade 4) was not associated with clinical bleeding. One patient had a grade 4 transient rise in transaminase. There was no grade 3 or 4 renal toxicity. There was no grade 4 symptomatic toxicity. The most common grade 3 toxicities were nausea and vomiting (28.2%) and alopecia (10.3%) both related to cisplatin. CONCLUSIONS: Gemcitabine can be safely administered at a dose of 1200 mg/m2 in combination with cisplatin. Thrombocytopenia seems to be less than in schedules with cisplatin given on day 1. The results of this studyshow promising activity (47.5% response rate) with modest toxicity. As this combination of gemcitabine and cisplatin deserves further evaluation in prospective randomized trials, the SLCG is comparing gemcitabine-cisplatin with etoposide-cisplatin in a phase III randomized study.

Adult↗
PubMed1998

Phase II trial of first-line high-dose ifosfamide in advanced soft tissue sarcomas of the adult: a study of the Spanish Group for Research on Sarcomas (GEIS)

BACKGROUND: The agent Ifosfamide (IFOS) is active against soft tissue sarcomas (STS), and patients who progress to IFOS at doses < or = 10 g/m2 show remissions when exposed to high-dose ifosfamide (HDI) (i.e., doses > 10 g/m2), which supports a dose-response relationship for this drug. Because of a lack of first-line studies in adult STS patients, we decided to test the activity and toxicity of HDI in a phase II trial. PATIENTS AND METHODS: Forty-eight patients were enrolled in the study. IFOS was administered at a dose of 14 g/m2 by continuous infusion over six days every four weeks. Granulocyte-macrophage colony-stimulating factor (GM-CSF) at 5 micrograms/kg/day for 10 consecutive days was systematically administered after an episode of neutropenic fever or a delay in hematologic recovery. Patients were treated until progression or the occurrence of severe toxicity, and surgical rescue was attempted when possible. RESULTS: Six pathology-established complete remissions and 11 partial remissions were observed in 45 assessable patients with a response rate of 37.7% (95% CI: 25.5%-50%). Grade 3-4 toxicity (% of cycles) was noted by hemoglobin (17%), leukocyte (75%), granulocyte (75%) and platelet (13%) counts in 158 evaluable cycles. GM-CSF was administered to 28 patients, and 25 suffered one or more episodes of neutropenic fever. Renal toxicity was mild and reversible with some degree of tubular and glomerular dysfunction detected in up to 60% of patients. Grade 3 CNS toxicity was observed in 32% of patients but only one required interruption of therapy. Sixty-four per cent of the patients had asthenia grade 2-3 and 20% were excluded from the study due to excessive toxicity. There was one treatment-related death. CONCLUSIONS: HDI is an active drug in first-line therapy against adult STS. Different administration schedules should be evaluated in an attempt to improve its therapeutic index.

Adult↗
PubMed1998

Seventy-two hour epirubicin infusion plus quinidine in unresectable and metastatic adenocarcinoma of the pancreas: a phase II trial.

Twenty-two previously untreated patients who had unresectable and metastatic pancreatic cancer were treated in a prospective phase II trial with high-dose continuous infusion epirubicin (45 mg/m2 once every 24 hours continuous infusion days 4 through 6) plus quinidine (495 mg once every 24 hours on days 1-6). There were no objective responses (0 of 18 evaluable patients). Subjective responses were achieved in 2 of 21 evaluable patients (9%), all of whom had good performance status (Eastern Cooperative Oncology Group: 0-1). Median survival was 5.7 months for the overall population. Two patients who exhibited symptomatic improvement achieved responses lasting 7 and 13 months, respectively. Toxicity was generally mild and tolerable. Little benefit regarding survival and quality of life was observed with the use of this regimen. The role in chemoresistance of mdrl, p53, and the mismatch repair system was examined.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[Reversible hyperparathyroid metabolic osteopathy secondary to parathyroid carcinoma].

Parathyroid carcinoma is a rare cause of hyperparathyroidism and metabolic osteopathy. The authors report a patient with parathyroid carcinoma who underwent 99mTc-Sestamibi parathyroid and 99mTc-MDP bone scanning. These techniques showed the parathyroid lesion and typical features of severe metabolic osteopathy respectively. The bone scan performed at only four months after surgery showed near complete resolution.

Bone Diseases, Metabolic↗
PubMed1997

Value of logistic discriminant analysis for interpreting initial visual field defects.

PURPOSE: The authors evaluate logistic discriminant analysis as a method for interpreting visual field results in initial stages of several ophthalmic diseases. METHODS: The authors retrospectively studied the visual field defects of 96 patients with early glaucomatous damage and prospectively studied 84 subjects with normal eyes (n = 28), cataracts (n = 27), diabetic retinopathy (n = 14), or hypertensive retinopathy (n = 15). The visual fields were examined at least twice with program G1 of Octopus 500 (Interzeag AG, Schlieren, Switzerland). Only one eye per patient was randomly selected and included in the study. The authors created a database with all visual field information provided by Octopus and applied logistic discriminant analysis (SAS Logistic Procedures, SAS Institute, Cary, NC) to obtain classification rules capable of qualifying visual field defects as glaucomatous or nonglaucomatous. The rules were tested with an independent sample. RESULTS: There were significant differences between the groups in the distribution of visual field defects tested by program G1. Logistic discriminant analysis correctly identified the glaucomatous or nonglaucomatous origin of the defects with a sensitivity of 65% to 85% and a specificity of 60% to 92%. CONCLUSIONS: Logistic discriminant analysis is a useful tool to aid in the interpretation of early glaucomatous and nonglaucomatous visual field defects.

Data Interpretation, Statistical↗
PubMed1997

Modified weekly regimen with vinorelbine as a single agent in unresectable non-small cell lung cancer.

After a 26% response rate was reported with a 20/mg/m2/week vinorelbine (VRL) dose, a multicenter phase II trial of a modified weekly VRL treatment protocol (30 mg/m2 days 1 and 8 every 21 days) for unresectable non-small cell lung cancer (NSCLC) was designed to determine its clinical activity, toxicity, and survival of treated patients. As myelotoxicity frequently precludes the administration of VRL, by suppressing the dose that would correspond to day 15 of a weekly protocol, we allowed bone marrow recovery to take place and avoided the administration of the drug at the nadir of the cycle. The trial included 71 consecutive, previously untreated patients with unresectable and measurable disease. A total of 297 three-week treatment courses were administered with an average of 4 courses per patient (range 1-11). Results showed that in spite of attaining a median dose intensity of 19 mg/m2/week, this modified weekly VRL treatment regimen has a low level of activity (7.5% response rate) in NSCLC. Although a more tolerable level of toxicity is achieved, in order to maintain its antitumor activity, the recommended dose of VRL when given alone for NSCLC treatment (30 mg/m2/weekly) should not be decreased.

Adult↗
PubMed1997

[Application of clinical guidelines in the management of pleural effusion].

To analyze compliance with recommendations on the diagnosis and treatment of pleural effusion (PE), we conducted a retrospective study of 60 consecutive patients with PE. Thirty had been treated on the internal medicine ward (IM) and 30 had been cared for in the pneumology unit (P). Twelve variables were studied: 3 reflected the efficacy of medical intervention and 9 were related to diagnostic and therapeutic procedures as recommended by the American Thoracic Society and the American College of Physicians. PE was generally managed in accordance with the aforementioned guidelines. However, a number of unnecessary analytical tests were performed on pleural liquid from the first thoracocentesis. Although IM patients were comparable to P ward patients as to age, sex and concurrent chronic disease, the mean hospital stay was shorter for P ward patients (16 days versus 18 days in the IM ward, p < 0.05), and the percentage for whom an etiological diagnosis had been achieved upon discharge was higher in the P group (56% of P patients versus 26% of IM patients, p < 0.002). More P group patients than IM patients were followed up after discharge (83% versus 40%, respectively; p < 0.001). There were no significant differences in the remaining variables. Within the limitations of any retrospective study, these results allow us to conclude that PE is generally managed in accordance with international guidelines at our hospital and that diagnostic efficacy is greater on the pneumology ward, where mean stay is shorter.

Aged↗
PubMed1996

Hepatic response to the oxidative stress induced by E. coli endotoxin: glutathione as an index of the acute phase during the endotoxic shock.

Reactive oxygen species are important mediators of cellular damage during endotoxic shock. In order to investigate the hepatic response to the oxidative stress induced by endotoxin, hepatic and plasma glutathione (total, GSH and GSSG), GSSG/GSH ratio as well as Mn-superoxide dismutase and catalase activities were determined during the acute and recovery phases of reversible endotoxic shock in the rat. A significant increase in liver and plasma total glutathione content was observed 5 h after endotoxin treatment (acute phase), followed by a diminution of these parameters below control values at 48 h (recovery phase). The significant increases of GSSG levels and GSSG/GSH ratio are indicative of oxidative stress occurring during the acute phase. Liver Mn-SOD activity showed a similar time dependency as the GSSG/GSH ratio; however, a marked decrease in the liver catalase activity was observed during the process. These results indicate the participation of liver glutathione in the response to endotoxin and the possible use of plasma glutathione levels and GSSG/GSH ratio as indicators of the acute phase during the endotoxic process.

Acute Disease↗