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Biomedical subjects

J J López

Publications and source records attributed to J J López.

14 recordsLinked to original sources

Mobilization of peripheral blood progenitor cells with a combination of cyclophosphamide, r-metHuSCF and filgrastim in patients with breast cancer previously treated with chemotherapy.

The objective of our study was to determine the effect of adding r-metHuSCF to Filgrastim and cyclophosphamide for mobilization of peripheral blood progenitor cells (PBPC), on collection of CD34(+) cells and engraftment after autologous stem cell transplant. Twenty-three patients with previously treated stage II-IV breast cancer received cyclophosphamide (3 g/m(2)), Filgrastim 5 microg/kg daily and r-metHuSCF 20 microg/kg daily. Two PBPC collections were performed on consecutive days starting the day the WBC count was above 7.5 x 10(3)/microl. Collection was performed between days +9 and +12 and the median number of CD34(+) cells collected was 9.9 x 10(6)/kg (1.1-53.1) and 6.6 x 10(6)/kg (1.4-33.8) for the first and second apheresis, respectively. Despite being previously treated patients, the target CD34(+) cell dose required for SCT was obtained in all patients. SCT was associated with rapid neutrophil and platelet engraftment and a highly significant correlation was observed between the number of CD34(+) cells infused and engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate local skin rash being the most frequently reported adverse event. In conclusion, addition of r-metHuSCF induces mobilization of a large number of CD34(+) cells which results in shortening of time to engraftment and hospitalization.

Adult↗

The role of granulocyte colony-stimulating factor (G-CSF) in the post-transplant period.

The administration of G-CSF post transplant has been shown to accelerate the time to neutrophil engraftment. However, this does not necessarily translate into a meaningful clinical benefit to the patient. This randomized study was designed to determine the role of G-CSF following transplantation in patients with breast cancer (BC). A total of 241 evaluable patients with BC were included. There were 200 patients with high-risk BC, and 41 had disseminated BC in complete remission. All patients received conventional dose chemotherapy prior to transplantation. Patients were mobilized with G-CSF, received the STAMP V regimen, were transplanted with > or = 2.5 x 10(6) of CD34(+) cells/kg and were then randomized to receive 5 microg/kg of G-CSF starting on the day of infusion (arm A), five days later (arm B), or no G-CSF (arm C). The need for transfusion support, infectious complications and length of hospitalization were the variables chosen to demonstrate clinical benefit. Patients receiving G-CSF reached 500 and 1000 neutrophils significantly faster (P = 0.001) than patients with no G-CSF. This translated into a significantly (P < 0.05) shorter hospitalization time for patients receiving G-CSF. Arm C was closed and, after recruiting 110 patients in arm A, and 106 in arm B, the significant difference in neutrophil recovery persisted with no difference in the time of hospitalization between arms A and B. Therefore, G-CSF significantly accelerates the time to neutrophil engraftment. This translates into a shorter time of hospitalization. There is no difference in this variable regarding the time of administering the G-CSF: day 0 vs day +5. Therefore, G-CSF on day +5 should be the standard in this setting.

Adult↗

A phase III randomized trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) versus cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) in patients with metastatic breast cancer.

One hundred patients with metastatic breast cancer were randomly selected to receive combined chemotherapy treatment with adriamycin (50 mg/m2) or mitoxantrone (12 mg/m2) associated with 5-fluorouracil (600 mg/m2) and cyclophosphamide (600 mg/m2) administered intravenously every 21 days with a maximum of ten cycles. All patients included in this study were under 75 years of age and had ECOG performance status of less than 4. They had not been treated previously with chemotherapy for metastatic disease. Patients treated with adjuvant chemotherapy, which could not have included anthracyclines, had to have relapsed at least 12 months after the completion of therapy. There were no statistically significant differences in pretreatment characteristics or metastatic disease location between the two groups. Ninety-four patients were assessable for response. No differences were observed in response rate or in survival between the groups. The response rate (complete response (CR) and partial response (PR)) was 68% (13% CR and 55% PR for CAF; 0% CR and 68% PR for CNF). Median survival for all patients was 19 months (18 months with CAF and 19 months with CNF). All patients were assessable for toxicity. There were no differences in gastrointestinal and cardiac toxicity. More grade I-II hematologic toxicity episodes (p < 0.001) and treatment delays (p = 0.05) due to leucopenia were observed with the CNF group, and more grade III alopecia (p < 0.001) was observed with the CAF group. Patients received further therapeutic manoeuvres after finishing the study with a sequential treatment consisting of hormonal therapy and chemotherapy with mitomycin (M) -vinblastine (Vbl) (M 10 mg/m2 day 1, Vbl 5 mg/m2 days 1, 15 and 29; maximum 5 cycles). This chemotherapy treatment was received by 32 patients, with a response rate of 34% and grade III-IV hematologic toxicity of 37%. Treatment with CNF can be considered a good alternative to CAF for first-line treatment of metastatic breast cancer. M-Vbl treatment is useful as second-line treatment in patients with prior adriamycin exposure.

Adult↗

Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer.

PURPOSE: A randomized trial was designed to compare cisplatin (CDDP) and fluorouracil (FU) versus carboplatin (CBDCA) and FU as neoadjuvant treatment in stage IV-M0 head and neck cancer to assess whether CBDCA-FU is better than CDDP-FU with regard to response and toxicity. PATIENTS AND METHODS: Patients were randomized to receive CDDP 100 mg/m2 intravenously on day 1 and FU 5,000 mg/m2 over a 120-hour continuous infusion, or CBDCA 400 mg/m2 over a 24-hour continuous infusion on day 1 and FU with the same schedule. Both regimens were repeated every 21 days. The patients received three courses of chemotherapy, excluding those who failed to achieve a partial response (PR) after the second course. Complete responders were treated with radiotherapy. The remaining patients underwent surgery if the tumor was resectable. RESULTS: Interim analysis was performed when 95 patients were included. The trial was stopped due to significantly better results in the control arm. Differences in response (P = .04) were favorable to CDDP-FU. Hematologic toxicity predominated in the CBDCA-FU arm (P < .001). Mucositis and vomiting predominated in the CDDP-FU arm (P = .03, P < .001, respectively). Favorable outcomes (complete response [CR] plus any grade of toxicity and PR plus grade 0 to 3 toxicity) predominated in the CDDP-FU arm (P = .02). Only the treatment assigned was associated with response (P = .02) and favorable outcomes (P = .009) in the logistic regression analysis. In the CDDP-FU arm, disease-free and overall survival were significantly better. Cox regression analysis showed that only treatment association with disease-free survival remains significant. CONCLUSION: Our results indicate that CDDP-FU is more effective than CBDCA-FU as neoadjuvant treatment in stage IV-M0 head and neck cancer.

Adult↗

Function preservation in stage III squamous laryngeal carcinoma: results with an induction chemotherapy protocol.

Until recently, standard treatment for stage III laryngeal carcinoma (LC) was total laryngectomy and radiotherapy. Recent data suggest that induction chemotherapy (ICH) plays a role in preserving function in advanced head and neck cancer. No reports to date prospectively evaluate ICH exclusively in stage III LC. The authors designed a sequential phase II trial to assess if ICH allowed a conservative treatment in this disease. The objective of the first part of the study was to rule out a complete response rate with ICH below 30% with P < .05. ICH protocol consisted of three courses of cisplatin 100 mg/M2 on day 1 and 5-fluorouracil 5000 mg/M2 continuous infusion over 120 hours. Radiotherapy was administered to patients who attained a complete response (CR). Functional surgery (FS) was planned for patients with partial response. A total laryngectomy followed by radiotherapy was performed when FS was not feasible. Fifty-two previously untreated patients (all males) with squamous stage III LC were diagnosed in our institution, and 46 were entered in the ICH trial. After 9 patients were included, data showed 7 (78%) CR, ruling out a CR rate of less than 30%. After ICH, a CR was achieved in 29 (63%) of 46 patients. At the end of treatment, 35 patients (76%) had a functioning larynx. With a median follow-up of 3 years, larynx function was preserved in 26 (57%) of 46 patients and in 64% of survivors. Four-year actuarial larynx function preservation, overall survival, and disease-free survival were 55%, 77%, and 67%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

99mTc-ADP: a potential agent for in vivo tumor detection.

The possibility of using 99mTc-labelled nucleotides as tumour seeking agents has been proposed by different research groups. We have recently reported the preparation of a 99mTc-ADP complex with a high radiochemical purity (> 95%), good in vitro and in vivo stability and promising biodistribution results when injected in mice bearing spontaneous mammary adenocarcinomas. Here we report the results of further investigations in animals with spontaneous neoplastic processes, including whole-body autoradiography in mice (20 minutes and 60 minutes post injection) and gamma-camera imaging studies in Wistar rats. Dynamic studies (up to 45 minutes) and static images (up to 18 hours) were acquired to determine the pharmacokinetics of 99mTc-ADP and the tumour/muscle and tumour/blood ratios. Blood-pool studies were also performed as a control. Tumours were visualized by autoradiography as was to be expected from the biodistribution studies. Dynamic studies showed a rapid blood clearance and a behaviour that fitted to a tricompartimental model. Radioactivity was rapidly taken up by the kidneys and excreted in the urine. No evidence of in vivo instability of the complex was observed. Tumour uptake reached the maximum values after 20 minutes post-injection. Tumour/blood and tumour/muscle ratios improved over time, enhancing tumour visualization. The best images were obtained after 3 hours post injection. In summary, our studies suggest that 99mTc-ADP is a promising radiopharmaceutical for tumour diagnosis.

Adenosine Diphosphate↗

[Peripheral T-cell lymphoma. Morphologic, immunophenotypic and immunogenotypic studies of 10 cases].

We describe the histopathology, immunophenotype and immunogenotype of 10 cases of peripheral T-cell lymphoma. The majority of patients showed disseminated disease at the time of diagnosis. From a histopathological view point the cases were classified into 5 types: T zone lymphoma (4 cases); Lennert lymphoma (2 cases); pleomorphic lymphoma, small all type (2 cases); pleomorphic lymphoma of medium-sized cell type (1 case); pleomorphic lymphoma of large cell type (1 case). In most of them the neoplastic cells demonstrated a mature T-cell phenotype: CD3+, CD4+, CD8-, CD43+, CD45RO+, CD45RA-, CD20- and surface immunoglobulins. All cases studied displayed gene rearrangements for the T-cell receptor beta chain while the immunoglobulins genes remained in germinal configuration. Antibodies against the human T-cell lymphotropic virus type I were not found in the 9 samples studied.

Adult↗

The use of radioiodinated alpha-fetoprotein for the scintigraphic detection of mouse mammary carcinomas.

Alpha-fetoprotein (AFP) is taken up by developing fetal cells but not by normal adult cells. This finding together with the resemblance between fetal cells and cancer cells suggests that malignant tissue could incorporate AFP in opposition to normal tissue. In the present work, we injected mice bearing spontaneous mammary adenocarcinomas with 131I-radioiodinated AFP. The scintigraphic images obtained with a gamma camera showed that 11 out of 12 carcinomas displayed strong radiolabelling with very low activity in the surrounding normal tissues. In addition, three non-neoplastic cystic lesions were found to be negative. The future implications of this result for tumour diagnosis, as well as the possible mechanisms of AFP uptake are discussed.

Adenocarcinoma↗

Peripheral blood CD34+ cell immunomagnetic selection in breast cancer patients: effect on hematopoietic progenitor content and hematologic recovery after high-dose chemotherapy and autotransplantation.

BACKGROUND: Tumor cells have been detected in mobilized peripheral blood of breast cancer patients, and they may contribute to tumor recurrence after the transplantation of peripheral blood progenitor cells. One of the most widespread technologies for tumor purging of the graft is immunomagnetic hematopoietic progenitor cell selection. STUDY DESIGN AND METHODS: The study assessed the effectiveness of a magnetic cell-separation system in selecting functional subpopulations of hematopoietic progenitors from 14 blood-derived harvests of 11 patients with high-risk breast cancer after mobilization following cytotoxic chemotherapy supported by granulocyte--colony-stimulating factor, as well as the feasibility of transplanting these selected subpopulations. RESULTS: CD34(+)-enriched cell fractions had a median purity of 93.0 percent (72.7-98.5%). The procedure yielded 52.6 percent of the CD34+ cell input (39.4-116.8%). Median recoveries of colony-forming units (CFUs) (36.87%) and cobblestone area-forming cells (CAFCs) (152.5%) were, respectively, 0.70 and 2.87 times those of CD34+ cells (52.6%). Moreover, CAFC efficiency in the positive cell fraction was 2.57 times that in the starting cell fraction. Peripheral blood neutrophil counts of 0.5 x 10(9) per L and platelet counts of 20 x 10(9) per L were reached after median times of 9 and 11 days, respectively. The number of transfused CAFCs per kg, CD34+ cells per kg, and postthaw CFU-granulocyte-macrophage per kg was correlated, respectively, with the speed of engraftment of neutrophils, platelets, or both. Tumor cells detected in one patient's peripheral blood were not found after CD34+ cell selection. CONCLUSION: Transplantation of immunomagnetically purified peripheral blood CD34+ cells does not increase transplantation-related morbidity. It induces a selective enrichment of more immature hematopoietic progenitors, which makes it suitable for use in cell expansion and gene therapy protocols.

Adult↗

[Value of radioguided surgery with dobutamine 99mTc-MIBI in persistent secondary hyperparathyroidism].

99mTc-MIBI is a radiopharmaceutical that has been successfully used for the detection of hyperfunctioning parathyroid glands and for radioguided surgery techniques. We report on the case of a 55 year old woman in hemodialysis, with secondary persistent hyperparathyroidism after total parathyroidectomy. The conventional double-phase 99mTc-MIBI parathyroid scintigraphy was negative. The study was repeated after sensibilization with intravenous low-dose dobutamine showing an area of increased focal uptake in the lower cervical region. With this finding, radioguided 99mTc-MIBI surgery was performed after dobutamine administration, using a hand held gamma probe. The technique was considered successful with the resection of parathyroid cervical tissue which was further confirmed as nodular hyperplasia. We conclude that this methodology has the potential of being a an useful tool for the intraoperative localization of remanent tissue in patients with secondary persistent/recurrent hyperparathyroidism.

Dobutamine↗

ROC analysis of diagnostic performance utilizing serum antiproteases in cancer patients.

Assessment of the accuracy of diagnostic procedures is made independent of diagnostic criteria by means of a receiver-operating-characteristics (ROC) curve. We performed ROC analysis for the major serum antiproteases: alpha-1-antitrypsin (A1AT) and alpha-2-macroglobulin (A2M), in 99 cancer patients compared with 71 normal individuals. A1AT and A2M were significantly higher in cancer patients (p less than 0.0005). By comparing true positive and false positive rates for different serum levels, ROC analysis showed that serum A1AT quantification seems more useful in clinical practice than serum A2M.

Adult↗

[Program for nursing certification in critical care].

This article presents the Nursing Certification Program in Critical Care through which the Spanish Society of Intensive Nursing and Coronary Units (SEEIUC) accredits, by means of a diploma, the professional competence of graduate nurses in the care of critically ill patients. The program describes the system of certification and focuses on the study material for the examination, which is grouped into eleven thematic units. The first exam will be held 10 June 1999 in Palma de Mallorca, coinciding with the XXV National Congress of the SEEIUC.

Certification↗