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Biomedical subjects

E Benito

Publications and source records attributed to E Benito.

At least 19 recordsLinked to original sources

[Osteoma and exostosis of the external auditory meatus: a clinical diagnosis].

Proliferative osseous lesions usually found in the external ear are exostoses and osteomata. In other sites they are clearly different entities, but in this location histopathologic differential features are not so reliable in the study of the specimens. An occlusive osteomata is shown, with the typical clinical presentation demonstrated in a multiplanar CT. Microscopically, the lesion consisted of mature bone trabeculae, separated by medular spaces with fibrovascular tissue, characteristic features of osteomata. However, in the most superficial areas, lines of bone apposition, like those in exostoses, were found. A literature review confirms the lack of specificity of the histopathologic study, so diagnosis is based on clinical data.

Aged↗

Role of platelet-activating factor in phosphatidylcholine secretion in primary cultures of rat type II pneumocytes.

This study was designed to investigate the effect of platelet-activating factor (PAF) in the secretory response of type II pneumocytes, that are involved in the synthesis and secretion of the pulmonary surfactant. PAF increased phosphatidylcholine secretion in a concentration-dependent manner in the 10(-5) - 10(-10) M range, with a maximum phosphatidylcholine secretion of up to 3.3 fold the basal values (3.4 +/- 0.3% phosphatidylcholine secreted). This effect was prevented by the synthetic PAF-receptor antagonist WEB 2086. A study of the mechanism through which PAF exerts its stimulatory effect was carried out adding different agents that are well known stimulants of phosphatidylcholine secretion. Thus, PAF increased the TPA- and terbutaline-stimulated phosphatidylcholine secretion, that are PKC and PKA activators respectively, suggesting the involvement of both protein kinases in the process. This involvement was further supported by the use of inhibitors of protein kinases and by the stimulation of cAMP production in type II pneumocytes incubated with PAF.

Animals↗

Isolation of AmphiCASP-3/7, an ancestral caspase from amphioxus (Branchiostoma floridae). Evolutionary considerations for vertebrate caspases.

Caspases are a large family of cysteine proteases that play an essential role as effectors of apoptosis in metazoans. Thirteen different caspases have been identified in vertebrates so far, and their function in apoptotic or inflammatory responses is well documented. We have taken advantage of the broadly accepted condition of amphioxus (Cephalochordata, Branchiostoma floridae) as the closest living relative to vertebrates to study the molecular evolution of caspases. Here we report for the first time the pattern of programmed cell death during development of cephalochordates. We also describe the isolation and functional characterisation of the first caspase related gene in amphioxus, which we named AmphiCASP-3/7. The amphioxus caspase is expressed throughout development, from the gastrula to larva stage. AmphiCASP-3/7 induced cell death when ectopically expressed in human HEK 293T cells, and the recombinant protein was inhibited by DEVD peptides. AmphiCASP-3/7 reflects the primitive condition of the executor vertebrates caspases -3 and -7, prior to vertebrate specific duplication. Interestingly, AmphiCASP-3/7 is functionally closer to vertebrate caspase-7, as shown by substrate specificity both in vitro and in MCF7 cells. Our phylogenetic and functional data help in drawing the evolutionary history of caspases, and illustrates an example of acquisition in vertebrates of novel functional properties after gene duplication.

Animals↗

Sentinel node localization in patients with non-palpable breast cancer.

The aim of this study was to demonstrate that radionuclide sentinel node detection can be applied to patients with non-palpable breast cancer. One hundred and ten consecutive women with unilateral breast cancer were studied. Group 1 was made up of 80 patients with palpable breast cancer (mean age, 58 years) and group 2 of 30 patients with non-palpable breast cancer detected mammographically (mean age, 55 years). Tc-nanocolloid (111 MBq) was injected peritumorally in palpable tumours, and in the tumour area (ultrasound guided) in non-palpable tumours. At 2 h post-injection, anterior and lateral scintigrams were obtained from patients in the supine position. The location of the sentinel node was marked on the patient's skin. Patients with non-palpable tumours were moved to the surgery room 3 h later, and those with palpable tumours 24 h later. The histopathological study included three haematoxylineosin sections and immunochemistry. All patients underwent axillary lymphadenectomy. The sentinel node was detected in 67 cases (84%) in group 1 and in 28 cases (93%) in group 2. In four patients (5%) in group 1 and two patients (7%) in group 2, no axillary sentinel node was detected in the surgical bed, although it had been seen in scintigraphy. In nine patients (11%) in group 1, neither scintigraphic nor surgical detection was successful. Skip metastasis was seen in six cases (10%) of palpable tumours and in one case (4%) of non-palpable tumours. It can be concluded that non-palpable breast tumours cannot be considered an exclusion criterion for sentinel node localization and biopsy. Ultrasonography-guided injection, followed by scintigraphic and surgical detection of the sentinel node, may help in the management of patients with non-palpable breast tumours.

Adult↗

Gamma probe sentinel node localization and biopsy in breast cancer patients treated with a neoadjuvant chemotherapy scheme.

The aim of this study was to analyse the accuracy of scintigraphic and gamma probe sentinel node (SN) localization in breast cancer patients who have been submitted to neoadjuvant chemotherapy (NC). Seventy-six patients with single breast cancer were included in the study, and were classified into two groups. Group 1 consisted of 40 women who had received NC, and Group 2 consisted of 36 women who did not receive NC. All patients received 111 MBq (3 mCi) of 99Tcm-nanocolloid in 3 ml, by peritumoural injection. Anterior and lateral thoracic scans were obtained 2 h post-injection. The following day (18-24 h post-injection) the patients underwent surgery and sentinel nodes were localized by using a gamma probe. Complete axillary lymph node dissection was performed in all patients. Histological analysis included haematoxylin-eosin in all cases and immunohistochemistry in 10 cases. In Group 1, SNs were localized in 36/40 patients, histological analysis was performed in 34 and there were four false negatives (22%). In Group 2, SNs were localized in 32/36 patients, histological analysis was performed in 29 and there were two false negatives (9%). Predictive negative values were 78% and 90% in Groups 1 and 2, respectively. In summary, sentinel node localization in breast cancer patients submitted to previous neoadjuvant chemotherapy is less accurate than in patients who do not receive this therapy. The procedure is not sufficiently accurate to localize the sentinel node, thus it cannot be recommended in these patients.

Adult↗

Terminal cancer. duration and prediction of survival time.

The duration of the terminal period of cancer allows us to determine its prevalence, which is necessary to plan palliative care services. Clinical prediction of survival influences access to palliative care and the healthcare approach to be adopted. The objective of this study was to determine the duration of the terminal period, the prognostic ability of healthcare professionals to predict this terminal period and the factors that can improve the prognostic accuracy. In the island of Mallorca, Spain, we followed 200 cancer patients at the inception of the terminal period. Twenty-one symptoms, quality of life, prognosis and duration of survival were measured. Using a Cox regression model, a predictive survival model was built. Median duration was 59 days; 95% confidence interval (CI)=49-69 days, mean=99 days. The oncologists were accurate in their predictions (+/-1/3 duration) in 25.7% of cases, the nurses in 21.5% of cases and the family physicians in 21.7% of cases. Errors of overestimation occurred 2.86-4.14 times more frequently than underestimation. In the final model, in addition to clinical prognosis (P=0.0094), asthenia (P=0.0257) and the Hebrew Rehabilitation Centre for Aged Quality of Life (HRCA-QL) Index (P=0.0002) were shown to be independent predictors of survival. In this study, the estimated duration of the terminal period was greater than that reported in a series of palliative care programmes, and survival was overestimated. Oncologists could estimate prognosis more accurately if they also take into account asthenia and HRCA-QL Index.

Adult↗

Involvement of calcium in the stimulation of phosphatidylcholine secretion in primary cultures of rat type II pneumocytes by Escherichia coli lipopolysaccharide.

The purpose of this study was to evaluate the mechanism by which Escherichia coli lipopolysaccharide stimulates the secretion of phosphatidylcholine in primary cultures of rat type II pneumocytes. The stimulatory effect of lipopolysaccharide on phosphatidylcholine secretion was additive to those of terbutaline and TPA (protein kinase A and C activators respectively) and this effect was not suppressed by inhibitors of both protein kinases. On the other hand, lipopolysaccharide did not modify the increase on phosphatidylcholine secretion induced by the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin, and enhanced slightly the calcium-ionophore A23187 stimulated phosphatidylcholine secretion. In addition, the stimulatory effect of lipopolysaccharide was suppressed by BAPTA, an intracellular Ca2+ chelator, and KN-62, a specific inhibitor of Ca2+-calmodulin-dependent protein kinase. These results, together with the lipopolysaccharide-mediated increase in the cytosolic [Ca2+], suggest that stimulation of phosphatidylcholine secretion by lipopolysaccharide in type II pneumocytes occurs by a calcium-dependent transduction mechanism via Ca2+-calmodulin-dependent protein kinase activation.

Adrenergic beta-Agonists↗

[Radioisotopic localization of the sentinel lymph node in breast cancer. Preliminary results].

The aim of this preliminary work is to show the results of the radioisotopic localization of the sentinel node in breast cancer and the surgical resection using a gamma probe. We studied 10 patients with breast cancer without primary chemotherapy and 3 patients with primary chemotherapy before surgery. A lymphoscintigraphy was made after injection of 111 MBq of Tc99m-nanocolloid in a volume of 3 ml. The scans were performed after 30 minutes, 2 hours, 4 hours and 24 hours after injection. We detected the node and then a skin mark was made. The next day, surgical resection of this node was performed, guided by a gamma probe. We detected all sentinel nodes but one: 12 sentinel nodes and 7 second echelon nodes. The mean time for a surgical detection was about 16 minutes. In our experience this technique allows an accurate localization of the sentinel node in patients with breast cancer. We are able to localize the node in the surgical room guided with gamma probe. The peroperatory evaluation by anatomopathological techniques shown the status of this node. All this, does not delay the surgical time.

Adult↗

[The rat's vomeronasal organ. Histochemical study with lectins].

A histochemistry study by means of lectins of vomeronasal organ or Jacobson's organ was performed in 5 Wistar rats. Vomeronasal organ is localized at the antero-inferior level of the septum and present two kinds of epithelium, an olfactory one and other respiratory, on the medial and on the lateral part, respectively. Olfactory epithelium shows a great reactivity to WGA lectin, moderate to PNA and weck to Con-A and SBA. In the respiratory epithelium the reactivity is moderate to DBA, PNa, SBA and WGA lectins for goblet cells, instead the periciliary sheat of mucus is reactive to all lectins but DBA and LTA.

Animals↗

The inflammatory cytokines tumor necrosis factor alpha and interleukin-1beta stimulate phosphatidylcholine secretion in primary cultures of rat type II pneumocytes.

Tumor necrosis factor alpha and interleukin-1beta increase surfactant secretion in type II pneumocytes in a time- and dose-dependent manner. This stimulatory effect was additive to that of lipopolysaccharide, suggesting that cytokines and lipopolysaccharide may exert their actions through different signal transduction pathways. Tumor necrosis factor alpha and interleukin-1beta did not modify the increase on phosphatidylcholine secretion induced by the direct protein kinase C activator tetradecanoylphorbol 13-acetate, whereas this effect was inhibited by the protein kinase C inhibitors bisindolylmaleimide (2 x 10(-6) M) and 1-(5-isoquinolinylsulphonyl)-2-methyl piperazone (10(-4) M). In addition, the stimulatory effect of tumor necrosis factor alpha and interleukin-1beta was not suppressed by the intracellular Ca2+ chelator BAPTA (5 x 10(-6) M) or by KN-62 (3 x 10(-5) M), a specific inhibitor of Ca2+-calmodulin-dependent protein kinase. These results suggest that tumor necrosis factor alpha or interleukin-1beta stimulate phosphatidylcholine secretion via protein kinase C activation in a Ca2+-independent manner.

Animals↗

Glucagon-like peptide-1-(7-36)amide increases pulmonary surfactant secretion through a cyclic adenosine 3',5'-monophosphate-dependent protein kinase mechanism in rat type II pneumocytes.

Glucagon-like peptide-1 (GLP-1) receptor messenger RNA has been identified in cells considered type II pneumocytes that are involved in the synthesis and secretion of the pulmonary surfactant. In an attempt to open new insights into the control of surfactant secretion, we studied the effects of glucagon-related peptides in this process. Accordingly, type II pneumocytes were isolated from Wistar rat lungs and cultured overnight with [methyl-14C]choline, and then the basal and stimulated secretions of [14C]phosphatidylcholine were measured. GLP-1(7-36)amide stimulated phosphatidylcholine secretion in a concentration-dependent manner in the 1-100 nM range; the concentration of the peptide that produced a half-maximal response was 10 nM. Exendin-4 induced similar effects. No changes were observed when GLP-1-(1-37), GLP-2, or exendin-(9-39) was added to the medium. However, the latter reversed the stimulatory effects of GLP-1-(7-36)amide and exendin-4. A study of the mechanism through which GLP-1-(7-36)amide exerts its stimulatory effect was carried out using different agents that are well known stimulants of phosphatidylcholine secretion. GLP-1-(7-36)amide did not produce any change in the stimulatory effect observed with terbutaline or 8-bromo-cAMP, suggesting the involvement of a cAMP-dependent protein kinase in the stimulatory effect of this peptide on phosphatidylcholine secretion. It was further supported by the use of inhibitors of protein kinases and by the stimulation of cAMP production in type II pneumocytes incubated with either GLP-1-(7-36)amide or exendin-4.

Adrenergic beta-Agonists↗

Impaired phosphatidylcholine biosynthesis and ascorbic acid depletion in lung during lipopolysaccharide-induced endotoxaemia in guinea pigs.

Injection of guinea pigs with a single dose of Escherichia coli lipopolysaccharide (3.2 mg/100 g) induces a reversible endotoxic shock that was evaluated by measuring plasma glucose levels and aspartate aminotransferase activity at 24 h after lipopolysaccharide injection. The hypoglycaemia and the increase in plasma aminotransferase activity observed, correlated with the alterations found during the recovery phase of endotoxic shock. When lipid peroxidation and some antioxidant systems were measured in lungs from treated animals, we only found differences in ascorbic acid content, that was decreased by 50%. Lipopolysaccharide treatment results in a depression of pulmonary phosphatidylcholine synthesis, that correlates with the surfactant deficiencies associated with respiratory illnesses in septic shock. Guinea pigs fed on a diet with a low content in ascorbic acid were more sensitive to endotoxin. In these animals we found no detectable levels of ascorbic acid in lung, whereas both vitamin E lung levels and pulmonary phosphatidylcholine synthesis were significantly decreased. Our results point out the significance of ascorbic acid in the protection against oxidative lung injury associated to endotoxaemia, and validate our shock model for further studies on the mechanisms of this pathological condition.

Animals↗

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies.

The objective of this study was to examine the effects of the intake of dietary fat upon colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. Original data records for 5,287 cases of colorectal cancer and 10,470 controls were combined. Logistic regression analysis was used to estimate odds ratios (OR) for intakes of total energy, total fat and its components, and cholesterol. Positive associations with energy intake were observed for 11 of the 13 studies. However, there was little, if any, evidence of any energy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01, 1.02, and 0.92 for quintiles of residuals of total fat intake (P trend = 0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (P trend = 0.39). The analysis suggests that, among these case-control studies, there is no energy-independent association between dietary fat intake and risk of colorectal cancer. It also suggests that simple substitution of fat by other sources of calories is unlikely to reduce meaningfully the risk of colorectal cancer.

Adult↗

Alterations in circulating fatty acids and the compartmentation of selected metabolites in women with breast cancer.

The presence of the tumor in women with breast cancer provokes a profile of biochemical change characterized by hypoglycemia, hyperuremia and high levels of free fatty acids and ketone bodies in plasma. The total circulating levels of amino acids and lactate are slightly higher in patients with breast cancer. Moreover, alterations in the circulating levels of free and total fatty acids are associated with enhanced levels of total free fatty acids and significantly lower levels of esterified arachidonic acid. This profile may indicate a state of moderate catabolic activation in breast cancer patients and may also be associated with a slight mobilization of proteins and fatty acids by some of the peripheral tissues in order to cover the needs of the host and the tumor. However, the alteration in the distribution of different fatty acids (saturated, mono-unsaturated and poly-unsaturated) and the different behaviour of the free and esterified fractions may be the result of a greater release of only specific fatty acids by tumor or other host tissues, rather than a higher release of the whole spectrum of free fatty acids. Thus, it is proposed that some of the alterations may be directly related to localized tumor activity.

3-Hydroxybutyric Acid↗

Ki-ras mutation modifies the protective effect of dietary monounsaturated fat and calcium on sporadic colorectal cancer.

The geographic differences in the incidence of colorectal cancer have been mostly attributed to variations in diet. The diversity of the Mediterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer sets the stage for investigating the possible association between dietary factors and mutations in tumor genes known to play a role in the pathogenesis of these neoplasms. With this purpose, we have studied the Ki-ras gene in 108 colorectal cancers using archival tissue and epidemiological data from our previous case-control study. Mutations in exon 1 of the Ki-ras gene were detected by a PCR-single strand conformation polymorphism approach. A polychotomous logistic regression model was used to assess the significance of observed differences between wild-type and mutated tumors with respect to population controls in the different categories of nutrient consumption. Multivariate density models were used to adjust the correlation between nutrients and total energy. Our studies show that high consumption of monounsaturated fats, mostly derived from olive oil, is associated with a statistically significant decrease in the risk of cancer with wild-type Ki-ras genotype but not of Ki-ras mutated cancers. Conversely, we find that high calcium intake is associated with a decreased risk of Ki-ras mutated tumors but not of wild-type tumors. Tumor genotyping can reveal epidemiological associations that are weak or unapparent when cases-control studies are not stratified by tumor genotype.

Aged↗

Rapid maxillary expansion. A study of the long-term effects.

A study was made to determine whether skeletal alterations usually produced by rapid maxillary expansion may be compensated for in time by growth and/or comprehensive orthodontic treatment. In 30 patients, orthodontic treatment was started with rapid maxillary expansion, followed by fixed appliances, not combined with any other form of orthopedic device. Mean treatment time was 3.1 years. Nine measurements from the Ricketts analysis were studied, based on lateral cephalometric radiographs. Records were taken before orthodontic treatment and after completion of active therapy. A statistical analysis was made of the nine variables used, reflecting the vertical and anteroposterior skeletal proportions of the face, contrasting the changes before and after treatment. Of all the variables studied, the four that change with age according to the Ricketts analysis (mandibular plane angle, maxillary height, facial depth and facial convexity), yielded statistically significant differences after treatment, indicative of normal growth. The five remaining variables that remain constant with age according to the Ricketts analysis (facial axis, lower facial height, total facial height, palatal plane inclination and maxillary depth) showed no significant changes after treatment, also indicative of normal growth.

Adolescent↗