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Biomedical subjects

E Castillo

Publications and source records attributed to E Castillo.

At least 19 recordsLinked to original sources

Impact of BRCA2 pathogenic variants on outcomes to first-line CDK4/6 inhibitors plus endocrine therapy in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Currently, three cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) are approved in combination with endocrine therapy (ET) as first-line treatment of patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). The impact of homologous recombination repair (HRR) pathogenic variants (PV) on outcomes with first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC remains uncertain. PATIENTS AND METHODS: We conducted a multicenter, real-world, case-control study including 233 patients with HR-positive/HER2-negative MBC treated with first-line CDK4/6i and ET. Among them, 116 presented HRR PVs and 117 were matched controls with negative germline testing. The primary objective was to compare progression-free survival (PFS) and overall survival among germline-BRCA2 PV carriers, other HRR PV carriers, and controls. To minimize baseline differences in prognostic factors between PV carriers and controls, inverse probability of treatment weighting was applied. Molecular analyses in pre-CDK4/6i samples among patients with BRCA2 PV were carried out, including RAD51-foci, PAM50 intrinsic subtype, and RB1 loss of heterozygosity (LOH). RESULTS: Among the included 233 patients, median age at diagnosis was 45 years (interquartile range 39-56) and 33% had de novo metastatic disease. Primary resistance to adjuvant ET was present in 10% and secondary resistance in 27%. After a median follow-up of 44 months, patients with germline-BRCA2 PVs (n = 67) had significantly shorter PFS [11 versus 27 months; adjusted hazard ratio (aHR) 2.73, 95% confidence interval (CI) 1.65-4.51, P < 0.001] compared with controls. Among patients with endocrine-sensitive disease, germline BRCA2 PV carriers had markedly shorter PFS (median PFS 12 versus 39 months; aHR 4.04; 95% CI 1.82-8.98, P < 0.001). Exploratory analyses revealed RB1 LOH before CDK4/6i-treatment in most evaluable BRCA2 tumors. CONCLUSIONS: BRCA2 PVs were independently associated with poorer outcomes to first-line CDK4/6i plus ET in HR-positive/HER2-negative MBC compared with controls, especially relevant among patients with endocrine-sensitive disease. These findings suggest that patients with a germline PV in BRCA2 may require alternative first-line strategies.

Humans

Effect of processing on some chemical and nutritional characteristics of pre-cooked and dehydrated legumes.

The effect of processing on chemical composition and protein quality of three legumes was studied. The species analyzed were beans (Phaseolus vulgaris), Tórtola and Coscorrón varieties; lentils (Lens esculenta), Laird variety; and chick peas (Cicer arietinum), California-INIA variety. The legumes were soaked in a solution of Na2 EDTA at 0.03% for 16 h and cooked for a predetermined period for each species. They were dried in a tray drier with cross currents of air flowing at a speed of 10 m/min until the residual moisture content was 8%. The water activity in the resulting products ranged from 0.574 to 0.587, thus completely assuring no microbial activity. No important changes were observed in the legumes protein, fat, or fibre contents after processing. The soaking solution was effective in reducing the phytic acid content from 2.99 to 1.64 mg/100 g in the Tórtola beans, which had the highest acid value prior processing. In all the species the heat treatment reduced the activity of the trypsin inhibitors by at least 50%. Cooking and drying significantly increased protein digestibility in all the legumes studied, with chick peas showing the most dramatic increase: form 54.7% pre-processing to 94.9% post-processing. With regard to Net Protein Ratio (NPR), chick peas had a value of 4.03, followed by Tórtola beans (3.29), Coscorrón (3.09) and lentils (2.61). The NPR value for the casein diet was 4.20.

Desiccation

Design of two immobilized cell catalysts by entrapment on gelatin: internal diffusion aspects.

Experimental results obtained during the design of two immobilized cell catalysts by entrapment on gelatin are presented. Strong diffusional limitations are found and explained with the usual parameters and models, introducing an empirical correlation between substrate concentration and effectiveness factor. The effect of particle size, enzyme load, and specific activity in the system is discussed in terms of cooperation between bioengineers and geneticists.

Catalysis

Clinical differentiation between lethal catatonia and neuroleptic malignant syndrome.

Lethal catatonia, a syndrome described several decades before the advent of neuroleptic drugs, has been regarded by many investigators as clinically similar to, and perhaps indistinguishable from, neuroleptic malignant syndrome. However, published case reports of the two syndromes indicate differences in mode of onset, signs and symptoms, and outcome. Lethal catatonia often begins with extreme psychotic excitement, which, if persistent, can lead to fever, exhaustion, and death. Neuroleptic malignant syndrome begins with severe extrapyramidally induced muscle rigidity. Because lethal catatonia often requires neuroleptic treatment and neuroleptic malignant syndrome necessitates immediate cessation of neuroleptics, their early clinical differentiation is important.

Acute Disease

Biodegradation of a polyurethane in vitro.

This study examines the effect of in vitro exposure to enzymes on the performance properties of Biomer, a segmented polyetherurethane used in a number of blood-contacting devices such as catheters, heart assist pumps, and chambers for artificial hearts. The ultrathin samples were treated with two proteolytic enzymes, papain and urease, for periods of 1-6 months at 37 degrees C. The treated Biomer samples were subjected to chemical and physical analysis. Effects of biodegradation by the enzymes were assessed by fatigue tests, gel permeation chromatography (GPC), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) analysis. Papain was found to be more effective in degrading the polymer than urease. Mechanisms for enzymic degradation are proposed.

Biodegradation, Environmental

[Supplementation of wheat flour with chickpea (Cicer arietinum) flour. I. Preparation of flours and their properties for bread making].

The feasibility of adding chick-pea flour substituting part of wheat flour in yeast-leavened bread-making in order to increase the protein value, was studied. A 70% extraction chick-pea flour of commercial granulometry (150 mu) was prepared. Wheat flours of 74% and 78% extraction were then blended with 5%, 10% and 15% of chick-pea flour. Every flour and blend were subsequently analyzed to determine protein, ash, fiber, fat and maltose content, as well as sedimentation, farinogram and bread-making. Addition of chick-pea flour increased protein, fiber, ash and fat content in the blends, not causing a severe effect on quality, even at the 15% level of substitution. Blends showed an increase in maltose content, W value and bread specific volume. Furthermore, breads prepared were of good quality even without the use of maturing agents.

Bread

[Supplementation of wheat flour with chickpea (Cicer arietinum) flour. II. Chemical composition and biological quality of breads made with blends of the same].

Experimental bread made of wheat flour complemented with 5, 10 and 15% chick-pea flour was studied, using wheat bread as control. Samples were analyzed for their proximal chemical composition and amino acids content. Crude fiber and protein increased from 0.36% to 0.55%, and from 14% to 17.6%, respectively, when 15% chick-pea flour was added. The lysine content increased as the level of supplementation was raised. Biological quality of proteins was measured in rats as protein efficiency ratio (PER) as well as apparent digestibility resulting in an increase of PER values from 0.90 to 1.34 and small variations in bread protein digestibility. Bread nutritive value was significantly improved by adding chick-pea flour.

Amino Acids

The effects of an enhanced inflammatory reaction on the surface properties of cast Biomer.

The ability of a biomaterial to withstand the rigors of the harsh biologic environment is an important consideration when considering a material for long-term biomedical applications. Using a cage implant system, the effects of an intense inflammatory reaction on cast Biomer have been investigated. The inflammatory response to cast Biomer was greatly increased by coimplanting Biomer films with a cytotoxic poly(vinyl chloride) (PVC) in rats for a period of 21 days. Cast Biomer films were characterized by weight, advancing contact angle with water in air, attenuated total reflectance infrared spectroscopy and scanning electron microscopy (SEM). The analyses were performed before any treatment, after autoclaving and sonication, and after 21 days implantation with the cytotoxic (PVC) in rats. The results of the study indicated that cast Biomer does not undergo significant chemical degradation when subjected to the effects of an intense inflammatory reaction for 21 days. Implantation does, however, lead to rearrangement that results in a more polar and hydrophilic surface, suggesting that the polymer adapts to the hydrophilic environment of the inflammatory exudate.

Animals

Roentgenographic features of the arthropathy associated with CPPD crystal deposition disease. A comparative study with primary osteoarthritis.

We assessed the radiological features of the arthropathy seen in patients with calcium pyrophosphate dihydrate (CPPD) disease or pseudogout. Standard AP projections of the hands, pelvis and knees were evaluated in 74 patients with pseudogout, 68 cases of primary osteoarthritis (OA) and 78 "normal" controls matched by age and sex. A grade from 0 to 3+ was assigned to each of the 4 variables of OA: joint space narrowing, sclerosis, osteophytosis and subchondral cysts. Radiographic findings of OA were more prevalent (p less than 0.005) and severe (p less than 0.001) in the group with pseudogout than in the controls. When the groups with pseudogout and primary OA were compared, no significant differences were found in the overall severity of radiographic changes with only minor differences in its distribution. The pseudogout patients had greater changes in the metacarpophalangeal joints and a lesser involvement of the trapeziometacarpal joints. No radiological differences were observed in patients meeting McCarty's criteria for clinical types A and C.

Aged

Loss of suppressor T cell function and circulating immune complexes in alcoholic cirrhosis.

In the present work Concanavalin-A-induced T suppressor function has been studied in 28 patients with active alcoholic cirrhosis and 22 patients with inactive cirrhosis. Control subjects were 14 alcoholics without liver disease and 70 healthy individuals with normal liver function tests. Suppressor T cell function was decreased in active alcoholic cirrhosis whereas this change was not observed in inactive cirrhosis nor in alcoholics without liver disease. The suppressor T cell activity of normal individuals was inhibited by heat-inactivated serum pretreatment of patients with alcoholic cirrhosis. The data suggest that there is some kind of serum factor in alcoholic cirrhosis able to affect lymphocyte suppressor activity. No linear correlation could be established between serum level of circulating immune complexes (CIC), determined by solid-phase C1q-binding assay, and suppressor T cell function. There were no differences between sera of alcoholic cirrhosis patients with or without CIC regarding their inhibition of suppressor T cell activity of normal individuals. These results suggest that these serum factors are not related to the presence of CIC.

Adult