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Biomedical subjects

F Ferrer

Publications and source records attributed to F Ferrer.

At least 19 recordsLinked to original sources

Postprandial changes in the distribution of apolipoprotein AIV between apolipoprotein B- and non apolipoprotein B-containing lipoproteins in obese women.

Plasma apolipoprotein AIV (apo AIV) level has been shown to be a good marker of triglyceride changes after a high-fat diet. However, the distribution of apo AIV between apo B- and non-apo B-containing lipoproteins (Lp) during the postprandial state has not been described as well as the influence of obesity on this distribution. Our aim was to study the influence of parameters related to obesity and insulin resistance on the postprandial changes in apo AIV-containing Lp after a high-fat meal in obese women. Twenty-three overweight or obese women (body mass index [BMI] ranging from 29.1 and 64.0 kg.1 m(-2)), for whom blood samples were taken after fasting overnight, participated in the study. Thirteen of these obese women were given a fatty meal and, in this case, blood samples were taken at fast and 30 minutes, 1, 2, 4, and 6 hours after ingestion of the fat meal. Apo AIV-containing particle families, Lp B:AIVf (family [f] of particles containing at least apo B and apo AIV) and Lp AIV non-Bf (family [f] of particles containing apo AIV, but free of apo B) were quantified by sandwich enzyme-linked immunosorbent assay (ELISA). When fasting, Lp B:AIVf and Lp AIV non-Bf did not correlate with any of the parameters related to obesity and insulin resistance, if one excepts a positive correlation between HDL-cholesterol (HDL-C) and Lp AIV non-Bf. Postprandial lipemia was associated with a trend towards an increase in the plasma levels of apo AIV-containing Lp 6 hours after fat ingestion. The postprandial peak of Lp B:AIVf and Lp AIV non-Bf occurred 2 hours after the triglyceride peak. The distribution between apo B- and non-apo B-containing Lp did not change after ingestion of the fat meal, if one excepts a tendancy towards a lower ratio of bound and nonbound forms at 8 hours. Fasting plasma Lp B:AIVf concentration correlated with the area under the curve (AUC) of plasma triglycerides (beta = 0.11, P <.02). In a multivariate analysis, BMI (beta = 51.85, P <.001), fasting triglycerides (beta = 431.08, P <.01), and low-density lipoprotein-cholesterol (LDL-C) (beta = 2638.57, P <.005) were independent and positive determinants of the AUC of Lp AIV non-Bf, while waist circumference (beta = -23.94, P <.001), cholesterol (beta = -1655.02, P <.01), and systolic blood pressure (beta = -6.34, P <.05) were negative and independent determinants of this AUC. Fasting Lp B:AIVf may represent a good marker of the postprandial triglyceride increase in obese women. Changes in apo AIV concentrations in apo B- and non-apo B-containing Lp after a fat meal depend mainly on the degree of obesity rather than on insulin resistance. This effect is more obvious for Lp AIV non-Bf than for Lp B:AIVf.

Adult↗

[The health status of the Gypsy community in Spain. A review of the literature].

INTRODUCTION: Gypsies form an ethnic minority settled in Spain in the 15th century. At present, this collective presents certain social, economic, and health inequalities in comparison with the remaining population. The need for health interventions among the gypsy population is well known. OBJECTIVE: To determine which health-related matters among the Spanish gypsy community had received attention in the literature, and whether their ethnic differences and social inequalities in health had been studied. METHODS: We reviewed the literature published in the last 20 years. An international Medline search was performed. We also searched national and local papers through the IME-CSIC (Spanish Medical Index) database and the Internet. RESULTS: There were 96 valid articles on health among Spanish gypsies, of which 62 were published in Spanish journals and 47 had been published within the previous 6 years. Fifty-seven studies were performed in hospitals, 20 in public health centers and 13 in primary care centers. Eighty-eight percent were observational studies. The most frequent topics were genetics or congenital anomalies (30%), transmissible diseases (21%), child health (11%) and health sociology (11%). Fifty-seven percent of the studies reported some social inequalities in health. DISCUSSION: The Spanish gypsy community constitutes a health risk group due to ethnic and genetic factors. Moreover, they also have strong social inequalities in health related to mortality and morbidity in transmissible, chronic and environmental diseases due to socioeconomic and cultural factors, as well as to insufficient access to and use of health services.

Health Status↗

Fibroblast growth factor-binding protein is a novel partner for perlecan protein core.

Perlecan, a widespread heparan sulfate proteoglycan, functions as a bioactive reservoir for growth factors by stabilizing them against misfolding or proteolysis. These factors, chiefly members of the fibroblast growth factor (FGF) gene family, are coupled to the N-terminal heparan sulfate chains, which augment high affinity binding and receptor activation. However, rather little is known about biological partners of the protein core. The major goal of this study was to identify novel proteins that interact with the protein core of perlecan. Using the yeast two-hybrid system and domain III of perlecan as bait, we screened approximately 0.5 10(6) cDNA clones from a keratinocyte library and identified a strongly interactive clone. This cDNA corresponded to FGF-binding protein (FGF-BP), a secreted protein previously shown to bind acidic and basic FGF and to modulate their activities. Using a panel of deletion mutants, FGF-BP binding was localized to the second EGF repeat of domain III, a region very close to the binding site for FGF7. FGF-BP could be coimmunoprecipitated with an antibody against perlecan and bound in solution to recombinant domain III-alkaline phosphatase fusion protein. Immunohistochemical analyses revealed colocalization of FGF-BP and perlecan in the pericellular stroma of various squamous cell carcinomas suggesting a potential in vivo interaction. Thus, FGF-BP should be considered a novel biological ligand for perlecan, an interaction that could influence cancer growth and tissue remodeling.

Amino Acid Motifs↗

Metanephric stromal tumor: a rare benign pediatric renal mass.

We report a rare case and description of a benign pediatric renal mass. To our knowledge, this tumor has never been described in urologic published reports. It is possible that the identification of this renal tumor could spare a child the toxic adjuvant chemotherapy that would be administered if confused with histologically similar tumors such as clear cell sarcoma of the kidney.

Adenofibroma↗

A novel method for the determination of basal gene expression of tissue-specific promoters: an analysis of prostate-specific promoters.

Because the toxicity of suicide gene therapeutics is directly related to basal promoter activity, we developed an assay to test for promoter "leakiness" using a diphtheria toxin mutant. Sequences of 15 prostate-specific gene promoter constructs were cloned in an expression plasmid (pBK; Stratagene, La Jolla, CA) backbone driving expression of an attenuated mutant of diphtheria toxin A (tox176). Low expression levels of the DT-tox176 result in significant protein synthesis inhibition reflected by a decreased expression of the luciferase activity of a simultaneously transfected CMV luciferase construct. ID50 (dose of plasmid with 50% luciferase inhibition) was calculated for each promoter construct in different cell lines. Highest transactivational activity (ID50 <75 ng) was found for the CMV promoter in all cell lines, which is in agreement with the dual luciferase assay findings. Unlike the dual luciferase findings, however, the DT-tox176 assay showed protein inhibition of CN65 (PSA promoter/enhancer) and PSE-hK2 (PSA enhancer and basal human kallikrein 2 promoter) in HEK293 and DLD cells indicating "leakiness" of these promoter constructs. Low basal promoter activity in nonprostate cell lines was found for the minimal PSA promoter, hK2, DD3, and OC promoters. The DT-tox176 assay can better predict basal promoter activity compared to less sensitive dual luciferase assay.

Biological Assay↗

Effect of cold-storage in the accumulation of bioreactive substances in platelet concentrates treated with second messenger effects.

BACKGROUND AND OBJECTIVES: The mandatory 5-day of shelf-life platelet concentrates (PCs) creates outdating and inventory control problems in blood banking. Moreover, storage of PCs at 22-24 degrees C has been associated with a time-dependent accumulation of pyrogenic cytokines, potentially harmful for recipients. Previous studies have shown that supplementation of PCs with ThromboSol, a mixture of second-messengers effectors, might allow storage of functionally active platelets at refrigerated temperature to be extended. This study further investigates this storage approach by comparing the accumulation of bioactive compounds in standard and refrigerated PCs. DESIGN AND METHODS: The PCs were supplemented with ThromboSol or a control solution and stored in parallel at 24 degrees C with continuous agitation or undisturbed at 4 degrees C. Samples were removed on days 1, 5, 9 of storage, and assayed for their content of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and anaphylatoxins C3a and C4a. RESULTS: Throughout storage, refrigerated PCs, both ThromboSol-treated and untreated units, displayed a slightly lower level of IL-6 and significantly lower concentration of IL-8 than conventionally stored PCs. ThromboSol slightly reduced the level of these cytokines in PCs. Throughout storage at 22 degrees C, an accumulation of anaphylatoxins C3a and C4a was seen both in both control and ThromboSol-treated PCs. This accumulation was significantly reduced in control PCs stored at 4 degrees C, but not in refrigerated PCs supplemented with ThromboSol. Cold-storage, with or without ThromboSol, had a minor effect on the accumulation of TGF-beta1 in PCs. INTERPRETATION AND CONCLUSIONS: Our data confirm that release of bioactive compounds during in vitro storage of PCs is a temperature-sensitive process. The ThromboSol-refrigeration system could be a useful alternative for extending storage of PCs, without increasing the accumulation of cytokines (IL-6, IL-8), known to be involved in febrile reactions in recipients. Nevertheless, this storage system has no benefit on the level of other bioactive compounds (TGF-beta1, anaphylatoxins C3a and C4a) in PCs.

Blood Platelets↗

External beam irradiation plus (192)Ir implant after breast-preserving surgery in women with early breast cancer.

PURPOSE: To provide more information for the clinician and to analyze the impact of the boost with brachytherapy on the local disease-free survival (LDFS), disease-free survival (DFS), specific overall survival (OS), and cosmesis, a retrospective study of external radiation therapy and (192)Ir implantation in early breast cancer at Institut Català d'Oncologia has been undertaken. PATIENTS AND METHODS: From 1986 to 1996, 530 patients were selected for this study with a median follow-up period of 39.5 months (range, 10-115 months). External radiation therapy (combined with brachytherapy) was administered postoperatively to the breast in all patients. Mean given dose was 48.7 Gy (range, 42-52 Gy) with external radiation therapy to the breast, and 16.8 Gy (range, 10-27 Gy) was the mean dose with brachytherapy. Variables have been tested for cosmesis. Univariate and multivariate analysis have also been carried out. RESULTS: Mean age of the patients was 54 years (range, 28-81 years). Stages were distributed as follows: 350 patients (66%) in Stage I, 173 in Stage II (32.8%), and 7 in Stage III (1.1%). Pathologic distribution was 445 patients with infiltrating ductal carcinoma (84%), 20 patients with infiltrating lobular carcinoma (4%), and 65 patients (12%) of a miscellaneous group. OS for the entire group was 89.4% and 85.9% at 5 and 7 years respectively. Probability of DFS was 81.7% and 70.1% at 5 and 7 years. The LDFS was 94.9% and 91.7% at 5 and 7 years. The MFS probability was 85.5% and 76.9% at 5 and 7 years, respectively. Univariate analysis demonstrated that age (older than 52 years), premenopausal status, moderate and high histologic grades (Grades II-III), and presence of intraductal comedocarcinoma were prognostic factors for local relapse. Multivariate analysis for local disease-free survival demonstrated that only perineural or muscular infiltration remain as prognostic factors. Tumor dose bed of 70 Gy or higher had a negative impact in breast subcutaneous fibrosis, whereas dose rate lower than 65 cGy/h was better for skin color at 2 years. CONCLUSION: We conclude that patients with early-stage breast cancer undergoing external radiotherapy and LDR brachytherapy can be effectively managed. Overall survival, long-term local control, and cosmetic control are excellent.

Adult↗

Utilization of screening mammography as a preventive practice prior to initiating a population-based breast cancer screening program.

Factors associated with the level of utilization of screening mammography as a preventive practice were analyzed prior to initiating a population-based breast cancer screening program. A questionnaire was used to collect information about screening mammography utilization during the last 4 years among women invited to enroll in the program. Sociodemographic and health factors, and health services utilization were studied. A screening mammography in the last 4 years had been performed on 59.3% of the 8867 women interviewed. The utilization of mammography was higher among women who were younger, had a higher education level, or had previous visits to a physician (P < 0.001). The variables more strongly associated with use of screening mammography were: visit to a gynecologist and performance of a pap smear. Also associated with the utilization of screening mammography were: personal history of breast pathology, family history of breast cancer, breast self-examination, and recent visit to a general practitioner. Self-perceived health presented an inverse relation with screening mammography use (P < 0.001). The use of screening mammography appears to have increased in recent years, although inequalities persist which the breast cancer screening programs help to modulate. Mammographic frequency only would be deemed appropriate by the European guidelines in fewer than one-half of the cases.

Breast Neoplasms↗

Evaluation of pooled platelet concentrates using prestorage versus poststorage WBC reduction: impact of filtration timing.

BACKGROUND: Concern for the undesirable consequences of transfusing passenger WBCs is leading to the general use of WBC-reduced platelet concentrates (PCs). However, the impact of prestorage versus poststorage WBC reduction on the quality of platelet products has not been clearly defined. STUDY DESIGN AND METHODS: Pooled PCs were WBC reduced before or after 5-day storage, by use of a WBC filter (PXL-8, Pall Corp.). Samples from pools were taken on days 1 and 5, before and after filtration, and on Day 9 of storage and assessed for cell counts, biochemical values, expression of platelet glycoproteins, thrombin generation, and content of IL-6, IL-8, TNFalpha, transforming growth factor beta1 (TGFbeta1), and anaphylatoxins C3a and C4a. RESULTS: Filtration of fresh and 5-day-stored pooled PCs via a PXL-8 filter was similarly efficient, rendering pools with low WBC counts (<1 x 10(6) cells) and high platelet recovery (>95%). No major changes were found in the metabolic behavior or the expression of platelet GPIb, GPIIb/IIIa, CD62, and CD63 in PCs filtered before or after storage. Filtration, either before or after storage, increased by less than 5 percent the proportion of CD62+ platelets. Moreover, no changes were found in the concentration of prothrombin fragments 1 and 2 and thrombin-antithrombin complexes in the pooled PCs derived from the time of filtration. Finally, prestorage WBC reduction abrogated the accumulation of IL-6 and IL-8, but it did not prevent that of anaphylatoxins C3a and C4a nor of TGFbeta1. However, filtration through a PXL-8 filter significantly reduced (40-90%) the amount of IL-8, C3a, and C4a in the filtrate. CONCLUSIONS: The timing of PXL-8 filtration of PCs has little impact on the efficiency of WBC reduction and on platelet recovery, and it does not seem to affect the quality of platelets or the generation of thrombin in the PCs. As regards the goal of reducing the amount of bioactive products in PCs, it remains uncertain as to whether prestorage WBC reduction fully eliminates the need for poststorage filtration. Prestorage filtration leads to low levels of IL-6 and IL-8 in PCs, but it does not impair the poststorage content of TGFbeta1 or anaphyla-toxins. By contrast, poststorage PXL-8 filtration removes significant amounts of C3a and C4a, and thus it might provide clinical benefits beyond those of prestorage WBC reduction.

Blood Preservation↗

Evaluation of leukocyte-depleted platelet concentrates obtained by in-line filtration.

BACKGROUND AND OBJECTIVES: The use of leukocyte-depleted platelet concentrates (PCs) is justified, yet questions remain regarding their properties. We have assessed the in vitro quality of WBC-reduced PCs obtained by using a new in-line filter. MATERIALS AND METHODS: Twenty blood units were randomized for standard component preparation, or for processing including in-line leukodepletion of platelet-rich plasma using an ATS(TM) PL Pall filter. The resultant PCs were compared during storage for several in vitro platelet quality parameters, content of cytokines and anaphylatoxins, and coagulation markers. RESULTS: In-line filtration of platelet-rich plasma through ATS PL was highly efficient rendering PCs with 99.93% less white blood cells (WBCs) than standard PCs. During storage for up to 9 days, leukocyte-depleted units displayed platelet content, biochemical parameters, and platelet surface expression of glycoproteins Ibalpha, IIb/IIa, CD62 and CD63, similar to those of standard units. However, in-line leukocyte-reduced PCs displayed no significant accumulation of IL-6 and IL-8 during storage in contrast to standard units. Moreover, while storage promoted complement activation with C3a and C4a liberation in both WBC-reduced PCs and standard units, the concentration of these anaphylatoxins after the 9-day storage period was higher in the former group. Finally, all units, standard and leukocyte-reduced, displayed a similar storage-promoted rise in TGF-beta(1), and a mild prolongation of activated partial thromboplastin and prothrombin times. CONCLUSION: In-line filtration during component preparation appears as an easy and effective procedure for obtaining prestorage leukocyte-depleted PCs. During subsequent blood bank storage, these WBC-reduced PCs display, in comparison with standard PCs, normal in vitro platelet properties, decreased accumulation of cytokines IL-6 and IL-8, and increased complement activation.

Anaphylatoxins↗

Impact of radiotherapy on local control and survival in uterine sarcomas: a retrospective study from the Grup Oncologic Català-Occità.

PURPOSE: In order to provide more information for the clinician and to analyze the impact of radiation therapy on the loco-regional disease-free interval (LRFI), disease-free interval (DFI) and specific overall survival (OS), a multicentric retrospective study of uterine sarcomas has been undertaken using cases reported to the Grup Oncològic Català-Occità (GOCO). PATIENTS AND METHODS: One hundred three patients were selected for this study with a median follow-up period of 49 months. Patients were restaged using the FIGO classification for endometrial adenocarcinoma. Radiotherapy was administered postoperatively to the entire pelvis in 52% of cases (54/103) and was combined with brachytherapy in 24 patients. Mean given dose was 48 Gy, with a 95% confidence interval of 45 to 50 Gy. Variables have been tested for homogeneity between hospitals. Univariate and multivariate analyses have also been carried out. RESULTS: Mean age of the selected patients was 59 years (range 35-84). Stages were distributed as follows: 66 patients (64%) in Stage I; 16 in Stage II (15.5%); 12 in Stage III (11.5%); 9 patients in Stage IVa (9%). Pathological distribution was 41.5% leiomyosarcoma, 39% mixed Mullerian tumours, 16.5% stromal sarcomas, and 2.9% of a miscellaneous group. Overall survival for the entire group was 63.7% and 56% at 2 and 5 years, respectively. Probability of LRFI reached 59.8% at 2 years and 57.4 at 5 years. The DFI at 2 and 5 years were 52.9 % and 48.7%, respectively. The LRFI probability was 41% and 36% at 2 and 5 years, respectively, without radiotherapy and reached 76% at 2 and 5 years among those patients treated with radiotherapy. There was also an increase in DFI probability because of the effect of radiotherapy, from 35% to 68.5% and from 33% to 53% at 2 and 5 years, respectively. The overall survival probability for patients treated with radiotherapy was 76% and 73% at 2 and 5 years, respectively and 51% at 2 years and 37% at 5 years without radiotherapy. Multivariate analysis demonstrated that radiotherapy improved LRFI, DFI, and overall survival. CONCLUSION: We conclude that postoperative radiotherapy in our series of patients diagnosed with uterine sarcoma has an impact on loco-regional and disease-free progression intervals and survival.

Adult↗

Quality assessment of platelet concentrates supplemented with second-messenger effectors.

BACKGROUND: While reducing the potential for bacterial contamination, the storage of platelet concentrates (PCs) at refrigerated temperatures is not routine, because of the induction of the so-called platelet storage lesion. As the modulation of second-messenger levels might help to overcome this drawback, a quality assessment of PCs treated with a mixture of second-messengers effectors known as ThromboSol was performed. STUDY DESIGN AND METHODS: The PCs were supplemented with ThromboSol or phosphate-buffered saline, and stored in parallel at 22 degrees C with continuous agitation or at 4 degrees C. At 1, 5, and 9 days, an in vitro quality assessment of the PCs was performed, including measurement of cell number, metabolic and integrity markers, platelet surface expression of glycoproteins, platelet response to ristocetin and thrombin, and levels of cyclic adenosine 3', 5' monophosphate (cAMP) and thromboxane B2 (TxB2). RESULTS: Control PCs stored at 4 degrees C underwent aggregation and displayed a significant decrease in the platelet number (40% on Day 5). By contrast, the ThromboSol-treated PCs maintained 80 percent of their initial platelet concentration after 9 days of storage at 4 degrees C. Compared to PCs stored at 22 degrees C, refrigerated PCs exhibited minor changes in metabolic values throughout storage, but the addition of ThromboSol induced a rise in metabolic rate during storage at 22 degrees C. Platelet responsiveness to both ristocetin and thrombin was maximally preserved in the ThromboSol-treated PCs stored at 4 degrees C. These units also maintained high levels of cAMP and low concentrations of TxB2 during storage. CONCLUSION: The pharmacologic supplementation of PCs with ThromboSol significantly favors the maintenance of in vitro integrity and responsiveness of platelets during extended storage at refrigerated temperature. This protective effect seems to be a consequence of the ability of ThromboSol's components to sustain high levels of cAMP and to inhibit TxB2 production during the entire extended-storage period.

Blood Banks↗

Clinical and analytical relevance of the combination of prothrombin 20210A/A and factor V Leiden: results from a large family.

We analysed the clinical and analytical features of 18 subjects from a Spanish family who bear several combinations of two prothrombotic mutations, factor V Leiden (FVL) and prothrombin 20210A. We identified three subjects homozygous for the 20210A prothrombin mutation which additionally were heterozygous for FVL. The combination of both mutations increases the risk of developing venous thrombotic episodes at the earlier age. However, even in association with FVL, the homozygous condition of the prothrombin 20210A mutation requires additional risk factors to induce a thrombotic event. Finally, the plasma level of factor II showed a significant relationship with the prothrombin genotype.

Adult↗

Primary small cell carcinoma of the esophagus: a review of the literature with emphasis on therapy and prognosis.

BACKGROUND: Few studies of patients with esophageal small cell carcinoma (SCC) have been conducted. Choice of treatment remains controversial. METHODS: The authors analyzed data on 199 evaluable esophageal SCC patients, selected from among 230 patients found in the literature, and a data extraction form that recorded 11 features was completed. To allow for the evaluation of prognostic factors that influenced survival, the patients were grouped according to limited stage (LS), which was defined as disease confined to the esophagus, or extensive stage (ES), which was defined as disease that had spread beyond locoregional boundaries. Univariate and multivariate analyses were performed. Treatment was categorized as either local or local with systemic; for the ES cases, the categories were defined as treatment versus no treatment. RESULTS: The tumor site was described in 178 cases (89%). Mean tumor size was 6.1. Pure SCC was found in 137 cases (68.8%), whereas 62 cases (31.2%) showed mixed SCC; 93 (46.7%) were LS, whereas 95 (47.7%) were ES. In 11 cases (5.5%), the stage was not determined. There was a significant difference in survival between patients with LS and those with ES (P < 0.0001). The median survival was 8 months for patients with LS and 3 months for those with ES. Univariate analysis of LS showed 3 significant prognostic factors: age (for patients age < or =60 years, the median survival was 11 months, whereas for those age >60 years, the median survival was 6 months), tumor size (for those with tumors < or =5 cm, the median survival was 12 months, whereas for those with tumors >5 cm, the median survival was 4 months), and type of treatment (with local plus systemic treatment, the median survival was 20 months, whereas with local it was 5 months). In multivariate analysis, tumor size (P = 0.007) and type of treatment (P < 0.001) were shown to be independent predictive variables. CONCLUSIONS: Esophageal SCC is an aggressive type of tumor. This study shows that there are significant differences between LS and ES and that in LS, both tumor size and type of treatment are possible prognostic factors.

Adult↗