PubMed Health⌕ Search

Biomedical subjects

E Aranda

Publications and source records attributed to E Aranda.

At least 73 records · Page 4Linked to original sources

Weekly first-line chemotherapy of metastatic breast cancer with cyclophosphamide and epirubicin.

Forty-six patients with metastatic breast cancer who had not received previous chemotherapy for advanced disease entered a phase II trial of weekly chemotherapy with cyclophosphamide (250 mg/m2) + epirubicin (25 mg/m2) for 16 weeks. The overall response rate was 61% (95% confidence limits, 47-75%), with 10 complete and 17 partial responses. Toxicity was mild and confined to nausea and vomiting and asymptomatic neutropenia (except in 2 cases). Sixty-three per cent of patients had no side effects. Weekly cyclophosphamide + epirubicin is an active and nontoxic regimen for patients with metastatic breast cancer who have had no prior anthracycline-containing adjuvant chemotherapy.

Adult↗

Total sialic acid in human and canine platelets does not change with the platelet age.

Total platelet sialic acid (SA) was measured in three experimental conditions: (1) human and canine platelet density subpopulations obtained by centrifugation in arabinogalactan gradients, (2) circulating canine platelets during recovery from experimental immune and mechanical thrombocytopenias, and (3) platelets obtained from a patient with chronic immune thrombocytopenic purpura before and after splenectomy. The density of human and canine platelets is, in part, determined by their age. We found no significant differences in total SA between high-density (HD) and low-density (LD) platelets (9.32 +/- 2.0 vs. 9.55 +/- 1.3 micrograms/mg of platelet protein in dogs and 9.02 +/- 2.3 vs. 9.10 +/- 2.9 micrograms/mg in humans). In the human and canine thrombocytopenic models, the entrance of new platelets from the bone marrow is followed by their aging in the circulation. In these models, no significant changes in total SA content were detected in sequential measurements during the recovery of the thrombocytopenia. Accordingly, we conclude that total SA in human and canine platelets is unrelated to their age in circulation. These results do not support the notion that the loss of SA from membrane glycoproteins determines the recognition and removal of platelets from the circulation.

Animals↗

Study of the sagittal condylar path in edentulous patients.

The inclination of the condylar path is a fundamental consideration in the prosthodontic treatment of the totally edentulous patient. The authors studied 55 patients at the University of the Basque Country, making three graphic registrations of the protrusive condylar movement on each side. Three examiners, working independently, used the tangential method to measure the angulation relative to Camper's plane. The results show that angulation varies greatly on each side and from one individual to another. In the treatment of edentulous patients, graphic registering techniques that can determine these variations should be used.

Aged↗

Changes in apyrase activity in uterus and mammary gland during the lactogenic cycle.

1. The purpose of this present research was to explore the possible roles of ATP-diphosphohydrolase (apyrase) in two tissues with high energetic demands during cell proliferation and differentiation. 2. Changes in apyrase activities during the pregnancy lactation cycle were examined in the rat uterus and mammary gland. 3. A significant decrease in apyrase activity (ATPase-ADPase) was observed in the pregnant uterus; this observation correlates with a minor inhibitory effect on platelet aggregation. 4. In mammary gland, the enzyme activity increases during lactation in parallel with an increase in blood supply, synthesis of glycoproteins and cell proliferation. 5. Apyrase activity did not change during the estrous cycle. Estradiol administration to rats slightly increased (20%) both ATPase-ADPase activities. 6. The probable function of apyrase is finally discussed, based on its substrate specificity and subcellular localization.

Animals↗

Etoposide (E) + epirubicin (E) + cisplatin (P) combination chemotherapy (EEP) in advanced gastric cancer: negative impact on clinical outcome. Spanish Cooperative Group for GI Tumor Therapy (T.T.D.).

One hundred nineteen patients with advanced gastric cancer were included in a study comparing EEP vs. FEM chemotherapy. The response rate was higher (30%) in patients on EEP than in those treated with FEM (p = 0.05). Severe leukopenia, anemia, alopecia and infection were significantly more frequent on EEP. In addition, because of its intrinsic toxicity, EEP chemotherapy has a negative impact on the performance status of patients treated with this regimen, more than half of whom presented at least one episode of severe symptomatic toxicity while on EEP chemotherapy. The median time to progression and median survival for EEP-FEM were 2.08-3.4 and 4.2-7.9 months, respectively. Our data do not support the use of EEP chemotherapy in patients with AGC.

Antineoplastic Combined Chemotherapy Protocols↗

A prospective randomized trial of continuous infusion 5-fluorouracil (5-FU) versus 5-FU plus cisplatin in patients with advanced colorectal cancer. A trial of the Spanish Cooperative Group for Digestive Tract Tumor Therapy (T.T.D.).

One hundred sixty consecutive patients with histologically confirmed colorectal cancer (advanced disease) without prior chemotherapy were entered in a randomized trial comparing 5-fluorouracil (5-FU) 1,000 mg/m2 intravenously per day for 5 consecutive days in continuous infusion versus cisplatin (CP) 100 mg/m2 on day 1 plus 5-FU as described on days 2 to 6. In both arms, treatment was recycled every 4 weeks. Both groups were well balanced for age, sex, colon or rectal origin, median time between diagnosis to advanced disease, performance status at entry, and visceral involvement. The overall response rate in the combination and in the single arm were 18 and 23%, respectively. There were no differences in time to progression (a median of 17.8 and 14.9 weeks for CP-5-FU and 5-FU, respectively) and in overall survival (a median of 71.2 and 59.6 weeks, respectively). The incidence of grade 3-4 emesis was significantly higher in the CP-containing chemotherapy (p = .00001). Our study has failed to demonstrate any clinical benefit from adding cisplatin to 5-FU in patients with cancer of the colon and rectum.

Adenocarcinoma↗

Glomerular localization of platelet factor 4 in streptococcal nephritis.

Since platelet factor 4 (PF4), a cationic (pI 7.6) platelet secretory protein, binds avidly to glomerular polyanions both in vitro and in vivo, and is implicated in neutrophil chemotaxis, we studied by indirect immunofluorescence microscopy the presence of PF4 deposits in glomeruli of patients with poststreptococcal nephritis (APSGN). Goat antihuman PF4 serum was used as primary antibody and fluorescein-conjugated IgG fraction of rabbit antigoat IgG as second antibody. Controls consisted of nonimmune goat serum or anti-PF4 serum preabsorbed with human PF4, as primary antibodies. Glomerular deposits of PF4 were demonstrated in renal tissues obtained by biopsy in 14 of 20 patients studied; the deposits were particularly intense in 9 patients. PF4 was bound to the mesangium and to the capillary walls. There was a significant positive correlation between intraglomerular deposits of PF4 and the levels of proteinuria (p = 0.024). These findings provide further evidence for a role of platelets in the pathogenesis of APSGN and suggest that PF4 may contribute to alter the glomerular permeability in this disease.

Adult↗

Treatment of advanced colorectal cancer with recombinant interferon alpha and fluorouracil: activity in liver metastasis.

A cohort of 35 patients with advanced colorectal cancer, not previously exposed to chemotherapy, were included in a phase II study exploring the combination of interferon-alpha, 9 MU subcutaneously three times weekly, and 5-fluorouracil 750 mg/m2/day during 5 consecutive days in continuous intravenous infusion followed with weekly bolus injection of fluorouracil 750 mg/m2. Of 33 cases evaluable for activity; 5 patients achieved partial response and 3 complete response for an overall response rate of 24% (95%; confidence limit 11-42%). Most of the responses were observed in liver metastases, response rate = 30% (95%; CL 13-53%), with little activity observed in other sites; response rate 3% (95%; CL 8-16%), p = .0006. The median time to progression and median overall survival were 16+ (range 1+ to 48+) and 21+ weeks (range 1+ to 52+). All patients were evaluable for analysis of toxicity. Severe mucositis and diarrhea, present in 14 patients were the limiting side effects. Two patients developed progressive renal toxicity and died. Weakness, myalgia, and nonneutropenic fever were observed frequently, one patient developed dementia. This combination is able to induce major responses in patients with advanced colorectal cancer, particularly in liver metastasis. Additional trials evaluating this approach are indicated.

Aged↗

Platelet 5-hydroxytryptamine increases with platelet age in dogs.

Thrombocytopenia was induced in mongrel dogs by two mechanisms: immunologically, by intravenous injection of heterologous antiplatelet antibody, and non-immunologically, by circulating the blood through glass beads in anesthetized animals. The platelet content of 5-HT was monitored before and during the recovery of the blood platelet counts. This period is associated with the normalization of the mean platelet survival time and with a progressive increase in the mean age of the circulating platelet population. A continuous increment in platelet 5-HT closely followed the increase in platelet counts in both models of thrombocytopenia, and a strong correlation was found between the platelet age and 5-HT content. These findings support the concept that platelets accumulate 5-HT during their physiological aging process, contradicting the notion that a negative balance in 5-HT content results at the end of their physiological lifespan in circulation. These results are not in conflict with the concept that circulating platelets release and re-uptake 5-HT.

Animals↗

ATPase-ADPase activities of rat placental tissue.

1. Calcium-stimulated ATPase-ADPase activities were studied in a microsomal fraction of rat placental tissue. 2. The kinetic characteristics correspond to those of ATP-diphosphohydrolase, also known as apyrase (E.C. 3.6.1.5). 3. These characteristics include the lack of specificity towards nucleoside di- and triphosphates, activation by Ca2+, Mg2+ or Mn2+, insensitivity to specific inhibitors of some ATPase and absence of an effect of sulphydryl reagents. 4. Chemical modification of tyrosine, tryptophan, arginine and carboxylic residues decreases both ATPase and ADPase activities. 5. The substrate analogue, 5'-(beta, gamma-methylene)triphosphate, protected both enzyme activities against all the modifying amino acid reagents tested. 6. Placental fractions (homogenate and microsomes) inhibit ADP-dependent platelet aggregation. 7. The solubilized microsomal enzyme has a molecular mass of 67 kDa by size-exclusion chromatography; the pI is 9.36. 8. A differential effect is observed on the activation produced by Concanavalin A on microsomal and solubilized fractions when treated in the presence and absence of alpha-methylmannoside.

Adenosine Triphosphatases↗

Sera from patients with colon, breast and lung cancer induce resistance to lysis mediated by NK cytotoxic factors (NKCF).

Natural killer (NK) cells are involved in the antitumoral immunologic mechanism. These cells act through the release of cytotoxic molecules defined as NK cytotoxic factors (NKCF). Inhibitory factors of NK and NKCF mediated lysis have been described in in vitro assays. This study evaluates the induction of resistance to NKCF cytotoxicity by sera from 27 patients with colon, breast and lung cancer. Addition of these sera to the cytolytic assay where K562 cells and concentrated NKCF were used, induced resistance to NKCF mediated cytotoxicity in 21 cases (77%). The sera from the group with metastasis blocked NKCF lysis more markedly than the group with local tumours. However, no differences were observed when the groups with colon, breast and lung cancers were compared. This blocking effect was not found to be related to gamma interferon (IFN) levels. In a previous study, we described a tumour factor (NK-RIF) produced by human cell lines derived from metastatic adenocarcinomas. This factor blocked lysis of tumour target cells by NK cells. Consequently, it is proposed that the release of similar tumour factors with a capacity to induce resistance to NKCF may be involved in tumour growth and metastatic spreading in in vivo.

Breast Neoplasms↗

Weekly high-dose infusion of 5-fluorouracil in advanced colorectal cancer.

18 patients with advanced colorectal cancer entered a phase I-II study of high-dose 48 h continuous infusion 5-fluorouracil (5-FU) for 6 weeks. 7 patients were included at the first dose level (3 g/m2) and only 1 had serious toxicity (grade 3 diarrhoea and mucositis). 7 patients were included at the second dose level (3.5 g/m2). 6 had a good tolerance to treatment, while the remaining patient had grade 4 leukopenia. 4 patients received 4 g/m2: 3 had severe toxicity (grade 4 diarrhoea, myelosuppression, mucositis, central nervous system), such that the entry of new patients was stopped. Anti-tumour activity was seen in 33% (95% confidence interval 13-59%) of the overall population. Only patients who had not had previous chemotherapy responded to treatment (response rate in this subgroup [43%, 18-71%]). The optimal dose of 5-FU was 3.5 g/m2 weekly for six cycles.

Aged↗

Comparative study of size, total protein, fibrinogen and 5-HT content of human and canine platelet density subpopulations.

The size, total protein, fibrinogen and 5-HT content were evaluated in density subpopulations of human and canine platelets fractionated in linear arabinogalactan gradients. The methodology was assessed to ascertain that platelet separation was by density and to discard artifactual changes and platelet release during the procedure. EDTA or PGE1 increased the size of human PRP-platelets, but not of dog platelets. In humans, high density (HD) platelets were 1.26 times larger and contained 1.88 times more fibrinogen, 2.23 times more 5-HT and 1.37 times more protein than low density (LD) platelets; in dogs, these density cohorts did not differ in protein content, but LD platelets were 1.29 times larger and had 1.33 times more fibrinogen and 5-HT than HD platelets. These findings suggest that cell density is mostly dependent on the protein content per unit volume of platelets (and not on dense bodies). The differences in fibrinogen and 5-HT content between HD and LD cohorts in humans and dogs may be related to platelet age. The difference in volume between HD and LD platelets in dogs is of uncertain interpretation.

Aging↗

Changes in platelet beta-thromboglobulin, fibrinogen, albumin, 5-hydroxytryptamine, ATP, and ADP during and after surgery with extracorporeal circulation in man.

Surgery with extracorporeal circulation (ECC) is associated with transient alterations of platelet function whose pathogenic mechanisms are not completely understood. To define further the platelet abnormalities, we determined the changes in platelet content of several granule-associated substances during and after ECC in patients subjected to aortocoronary bypass surgery. Platelet beta-thromboglobulin (beta-TG) decreased to 79.8% of the preoperative level at the end of ECC (p less than 0.01) and, as expected, did not recover 1 hr after the end of surgery. Platelet fibrinogen and albumin decreased to 67.9% (p less than 0.01) and to 29.8% (p less than 0.01) of baseline, respectively. However, 1 hr after surgery, platelet fibrinogen rose to 92% and albumin to 55.5% of baseline, denoting that during the recovery from ECC, platelets incorporate some plasma proteins. During ECC, platelet 5-hydroxytryptamine (5-HT) and total ATP and ADP decreased to 50.8% (p less than 0.01), 63.2% (p less than 0.01), and 69.9% (p less than 0.01) of their respective preoperative values, indicating dense body release. One hour after surgery, ATP recovered to 83.8%, suggesting that previous depletion compromised also the metabolic pool of adenine nucleotides. In summary, Our results confirm and extend previous observations demonstrating alpha-granule release during ECC. Platelets undergoing ECC can incorporate plasma proteins as evidenced by the rapid increase of platelet fibrinogen and albumin after bypass. Although the mechanisms of this increase and site of storage of the exogenous substances are unknown, this observation justifies further studies to determine if internalization of plasma proteins, especially fibrinogen, may take place in physiological conditions. Dense body depletion with transient storage pool deficiency appears to be a component of the reduced platelet function during ECC. Consumption of metabolic ATP with alteration of platelet energy metabolism may further impair platelet function, contributing to the bleeding episodes observed during surgery with ECC.

Adenosine Diphosphate↗