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Biomedical subjects

R Simó

Publications and source records attributed to R Simó.

At least 19 recordsLinked to original sources

Clinical significance of RET/PTC and p53 protein expression in sporadic papillary thyroid carcinoma.

AIMS: Rearranged during Transfection (RET)/papillary thyroid carcinoma (PTC) and p53 are two genes involved in the pathogenesis of PTC. It has been suggested that RET/PTC expression is associated with higher rates of local extension and lymph node involvement, whereas p53 mutations are more frequent in poorly differentiated and anaplastic carcinomas. In addition, experimental studies have shown that p53 activity can modify the behaviour of PTC carrying RET/PTC. The aim of this study was to investigate the expression of both RET/PTC and p53 in order to evaluate their usefulness as prognostic factors. METHODS AND RESULTS: Resected specimens of 61 cases of PTC were studied immunohistochemically using a polyclonal antibody to RET and a monoclonal antibody to p53 protein. RET/PTC expression was associated with extrathyroid extension of PTC, at diagnosis (P < 0.05). In contrast, no relationship between p53 immunoreactivity and clinical status was found. In addition, p53 expression was more prevalent among RET/PTC+ patients, and significantly influenced the relationship observed between RET/PTC and extrathyroid extension of the disease. CONCLUSION: Our results suggest that immunohistochemistry for both PTC/RET and p53 could be useful in the clinical evaluation of patients with PTC.

Adult↗

Effect of growth hormone in an experimental model of protein hypercatabolism induced by glucocorticoids.

OBJECTIVE: The aims of the study were to evaluate whether growth hormone could be beneficial in a model of hypercatabolism induced by glucocorticoids and to examine its effects on ACTH, corticosterone and IGF-1 levels. The effects of growth hormone on the expression of both glucocorticoid receptor and tyrosine aminotransferase were also evaluated. METHODS: Fifty Wistar rats were divided into five groups and treated as follows: (A) daily subcutaneous injection of growth hormone (4.8 IU/kg/day) and oral placebo, (B) daily injection of placebo and oral dexamethasone (3 mg/kg/day), (C) daily injection of growth hormone and oral dexamethasone, (D) daily injection of placebo and oral placebo, and (E) no treatment. The animals were decapitated seven days after initiating treatment. RESULTS: Growth hormone did not modify the weight loss induced by dexamethasone. Glucocorticoid receptor expression was significantly lower in group A than in group E. An increase in tyrosine aminotransferase was observed in group C. CONCLUSION: Growth hormone did not exert any beneficial effect in this model of hypercatabolism. Growth hormone decreased glucocorticoid receptor expression. This fact could explain its beneficial effect when protein hypercatabolism is not the predominant phenomenon. Growth hormone induced the hyperexpression of tyrosine aminotransferase, thus suggesting an amplifying effect on the glucocorticoid action.

Adrenocorticotropic Hormone↗

Soluble transferrin receptors and ferritin in Type 2 diabetic patients.

AIM: To determine circulating transferrin receptor levels (sTfR) in Type 2 diabetic patients to evaluate whether serum ferritin reflects iron body stores or inflammation in diabetic population. METHODS: A total of 84 consecutive Type 2 diabetic patients and 60 healthy subjects matched by age and gender were included in this case-control study. Ferritin concentration was measured by a turbidimetric method and sTfR concentration were determined by nephelometry. RESULTS: Diabetic patients have higher serum ferritin levels than control subjects [114 ng/ml (12-831) vs. 74 ng/ml (11-697); P = 0.006]. However, no differences in sTfR concentrations were observed between both groups [1.27 mg/l (0.69-2.47) vs. 1.24 mg/l (0.77-2.80); P = NS]. A negative correlation between ferritin and sTfR concentration was detected in control subjects but not in diabetic patients. CONCLUSIONS: Serum ferritin levels are increased in Type 2 diabetic patients in the absence of a reciprocal decrease of sTfR. This finding suggests that elevated ferritin levels in Type 2 diabetes are mainly as a result of inflammatory mechanisms rather than iron overload.

Adult↗

Interleukin-8, monocyte chemoattractant protein-1 and IL-10 in the vitreous fluid of patients with proliferative diabetic retinopathy.

AIMS: To determine the intra-vitreous levels of two pro-inflammatory cytokines [interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1)] and the anti-inflammatory cytokine interleukin-10 (IL-10) in patients with proliferative diabetic retinopathy (PDR). In addition, the relationship between the profile of cytokines and PDR activity has also been evaluated. PATIENTS AND METHODS: The study included 22 consecutive diabetic patients with PDR (4 Type 1 and 18 Type 2) on whom a vitrectomy was performed. Sixteen age-matched non-diabetic patients with other conditions requiring vitrectomy, but in which the retina was not directly affected by neovascularization served as a control group. IL-8, MCP-1 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The vitreal levels of both IL-8 and MCP-1 were strikingly higher in diabetic patients with PDR in comparison with the control group [173.5 (64-1670) vs. 49 pg/ml (25-145), P < 0.001, and 2171 (388-6155) vs. 438 pg/ml (207-1344), P < 0.001, respectively]. In addition, the vitreous concentrations of IL-8 and MCP-1 were higher in patients with active PDR than in those patients with quiescent PDR [324.5 (80-1670) vs. 173.5 pg/ml (64-487), P = 0.06 and 3596 (1670-6155) vs. 1143 pg/ml (388-2500), P = 0.01, respectively]. However, vitreal levels of IL-10 in diabetic patients were similar to that obtained in the control group [2.89 (1.55-5.50) vs. 2.46 pg/ml (2.2-5.41), P = NS]. CONCLUSIONS: The pro-inflammatory cytokines IL-8 and MCP-1 are increased in the vitreous fluid of PDR patients without an increase in the anti-inflammatory cytokine IL-10. In addition, both IL-8 and MCP-1 intra-vitreous levels correlated with PDR activity, thus suggesting that these cytokines may be pathogenically important in PDR.

Aged↗

Intravitreous levels of hepatocyte growth factor/scatter factor and vascular cell adhesion molecule-1 in the vitreous fluid of diabetic patients with proliferative retinopathy.

OBJECTIVE: Hepatocyte growth factor, also know as the scatter factor (HGF/SF) has been involved in the etiopathogenesis of proliferative diabetic retinopathy (PDR). To further explore this issue we have determine the intravitreous levels of HGF/SF taking into account the problems that could lead to misinterpretation of the results when the vitreous fluid is used to indirectly explore the events that are taking place in the retina. In addition, the relationship between HGF/SF and vascular cell adhesion molecule 1 (VCAM-1) was also investigated. PATIENTS AND METHODS: Serum and vitreous samples were obtained during vitrectomy from 22 diabetic patients with PDR and 25 non-diabetic control subjects. Patients in whom intravitreous hemoglobin was detectable were excluded. A correction for plasma levels of either HGF/SF and VCAM-1 and intravitreal proteins was performed. RESULTS: Vitreal levels of both HGF/SF and VCAM-1 were higher in patients with PDR in comparison with the control group (p<0.001 and p=0.003, respectively). However, after correcting for total vitreal proteins both HGF/SF and VCAM-1 (ng/mg of proteins) were lower in diabetic patients than in non-diabetic control subjects (p=0.03 and p<0.0001, respectively). No relationship between the vitreous levels of either HGF/SF or VCAM-1 with PDR activity was detected. Finally, a correlation between the vitreal levels of HGF/SF and VCAM-1 was observed in diabetic patients (r=0.61, p=0.005) but not in the control group. CONCLUSION: Our results suggest that intraocular production of HGF/SF might be more important in mediating inflammatory and fibroproliferative processes rather than in angiogenesis itself.

Diabetic Retinopathy↗

Lymphocytic hypophysitis successfully treated with azathioprine: first case report.

An aggressive case of lymphocytic hypophysitis is described which was successfully treated with azathioprine after failure of corticosteroids. The patient, aged 53, had frontal headache, diplopia, and diabetes insipidus. Cranial magnetic resonance imaging (MRI) showed an intrasellar and suprasellar contrast enhancing mass with involvement of the left cavernous sinus and an enlarged pituitary stalk. A putative diagnosis of lymphocytic hypophysitis was made and prednisone was prescribed. Symptoms improved but recurred after the dose was reduced. Trans-sphenoidal surgery was attempted but the suprasellar portion of the mass could not be pulled through the pituitary fossa. Histological examination confirmed the diagnosis of lymphocytic hypophysitis. Two months later he developed aseptic meningoencephalitis which was treated with high dose methylprednisolone pulse therapy. MRI revealed a progression of suprasellar mass. At this stage azathioprine treatment was begun. Four weeks later MRI shown no evidence of residual lesion and no pituitary stalk enlargement. After follow up of 18 months without azathioprine there was no clinical or radiological evidence of the disease. This is the first evidence of the efficacy of azathioprine treatment in a patient with lymphocytic hypophysitis.

Adrenal Cortex Hormones↗

Studying marine microorganisms from space.

Microorganisms are but a few micrometers in diameter and are not visible to the naked eye. Yet, the large numbers of microorganisms present in the oceans and the global impact of their activities make it possible to observe them from space. Here a few examples of how microorganisms can be studied from satellites are presented. The first case is the best known: the main pigment used in photosynthesis (chlorophyll a) can be determined from satellites. These kinds of studies have contributed a tremendous amount of understanding about the distribution and dynamics of primary production in the oceans. Two other examples will concern analysis of heterotrophic prokaryotic production and estimates of dimethyl sulfide (DMS) concentration and flux to the atmosphere. These three processes are of fundamental importance for the functioning of the biosphere. Marine microbes carry out about half of the total primary production in the planet. A substantial fraction of the respiration in the oceans is due to the activity of heterotrophic prokaryotes. Finally, the flux of DMS to the atmosphere is believed to constitute one of the mechanisms by which the biota can regulate climate. The global implications of microbial processes in the oceans can only be addressed with the help of satellites.

Chlorophyll↗

Nitric oxide and vascular endothelial growth factor concentrations are increased but not related in vitreous fluid of patients with proliferative diabetic retinopathy.

AIMS: Several reports have implicated nitric oxide (NO) in the angiogenic process. The assessment of NO stable end products, nitrite and nitrate (NOx), is commonly used as a measure of NO production in biological fluids. The aims of the study were to investigate NOx concentrations in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to evaluate the relationship between NOx and vascular endothelial growth factor (VEGF). PATIENTS AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the time of vitreoretinal surgery from 23 patients with PDR, and 17 control non-diabetic patients with non-proliferative ocular disease. NOx was determined by using the Griess reaction and VEGF levels were assessed by ELISA. RESULTS: The intravitreous concentration of NOx was significantly elevated in patients with PDR in comparison with the control group (31.6 +/- 2.96 micromol/l vs. 18 +/- 2.46 micromol/l; P = 0.01). However, we did not detect any differences between NOx serum concentrations. We observed a correlation between serum and vitreous levels of NOx in diabetic patients (r = 0.79; P < 0.001), but not in the control group. Intravitreous levels of VEGF in patients with PDR were higher than those obtained in serum (1.42 ng/ml (0.12-7.62) vs. 0.12 ng/ml (0.03-0.42); P < 0.01). Vitreal levels of VEGF were strikingly higher in patients with PDR than in the control subjects (1.42 ng/ml (0.12-7.62) vs. 0.009 ng/ml (0.009-0.04); P < 0.001). No correlation between vitreal concentrations of NOx and VEGF was observed, either in diabetic patients or in the control group. CONCLUSIONS: NOx and VEGF are increased but not related in the vitreous fluid of diabetic patients with PDR. Our results suggest that serum diffusion could play a significant role in explaining the increase of NOx. By contrast, intraocular production seems to be the main factor responsible for the intravitreous enhancement of VEGF.

Diabetes Mellitus, Type 1↗

Production of atmospheric sulfur by oceanic plankton: biogeochemical, ecological and evolutionary links.

Biological production of the volatile compound dimethylsulfide in the ocean is the main natural source of tropospheric sulfur on a global scale, with important consequences for the radiative balance of the Earth. In the late 1980s, a Gaian feedback link between marine phytoplankton and climate through the release of atmospheric sulfur was hypothesized. However, the idea of microalgae producing a substance that could regulate climate has been criticized on the basis of its evolutionary feasibility. Recent advances have shown that volatile sulfur is a result of ecological interactions and transformation processes through planktonic food webs. It is, therefore, not only phytoplankton biomass, taxonomy or activity, but also food-web structure and dynamics that drive the oceanic production of atmospheric sulfur. Accordingly, the viewpoint on the ecological and evolutionary basis of this amazing marine biota-atmosphere link is changing.

Journal Article↗

Islet cell and thyroid antibody prevalence in patients with hepatitis C virus infection: effect of treatment with interferon.

An increased prevalence of hepatitis C virus (HCV) infection in patients with diabetes and a higher prevalence of diabetes in HCV-infected patients have been reported. However, the relationship between these two conditions remains controversial. In addition, although the effect of interferon treatment on thyroid autoimmunity has been extensively reported, its influence on beta-cell autoantibodies has not been investigated. The aims of the study were (1) to evaluate whether autoimmune beta-cell damage could be involved in the development of diabetes mellitus in HCV-infected patients and (2) to determine whether interferon treatment influences the appearance of beta-cell and thyroid autoantibodies. The prevalence of islet cell autoantibodies (glutamic acid decarboxylase antibodies [GADAs], tyrosine phosphatase antibodies [IA-2s], islet cell antibodies [ICAs]) was assessed in 303 non-selected HCV-infected patients (277 non-diabetic and 26 type 2 diabetic patients) and in 273 sex- and age-matched control subjects. ICAs and thyroid autoantibodies were also determined before and 6 and 12 months after treatment with interferon for 24 weeks in a subgroup of 46 HCV-infected patients. GADAs were detected in 4 of 277 (1.4%) HCV-infected non-diabetic patients, 1 of 273 (0.3%) control subjects, and 0 of 26 (0%) HCV-infected patients with diabetes. Anti-IA2s and ICAs were negative in all subjects. Both GADAs and anti-IA2s were negative in all HCV-infected patients treated with interferon. After therapy, only thyroid antibodies became positive in 5 of 46 (10.9%) treated patients, disappearing in all but 1 of these at the 12-month follow-up. Our results suggest that beta-cell autoimmunity is not associated with HCV infection, thus making it unlikely that the increased diabetes mellitus prevalence among HCV-infected patients could be mediated by autoimmune mechanisms. In addition, interferon treatment induces a transient increase in thyroid autoantibodies but does not influence the appearance of beta-cell autoantibodies.

Adult↗

nm23-H1 immunoreactivity as a prognostic factor in differentiated thyroid carcinoma.

Several prognostic factors have been proposed to identify the patients at risk to develop metastases in differentiated thyroid carcinoma. Reduced nm23-H1 expression (a metastatic suppressor gene) has been correlated with high tumor metastatic potential in various human carcinomas, but the results obtained in differentiated thyroid carcinoma remain controversial. To elucidate the usefulness of nm23-H1 as a differentiated thyroid carcinoma prognosis factor, we evaluate the relationship between nm23-H1 immunoreactivity as well as both clinical status and patient outcome. For this purpose, thyroid resected specimens obtained from 94 differentiated thyroid carcinoma consecutive patients (64 papillary and 30 follicular) with at least 5 yr of follow-up were stained using monoclonal antibody to nm23-H1. We did not observe any relationship between nm23-H1 immunoreactivity and age, gender, initial differentiated thyroid carcinoma stage, local recurrence, or distant metastases in patients with papillary carcinoma. However, in patients with follicular carcinoma, a significant inverse association between metastatic disease and the expression of nm23-H1 product was obtained (P < 0.05). In addition, significant differences were found in the survival curves according to nm23-H1 immunoreactivity (log-rank P < 0.01). Finally, nm-23-H1 immunoreactivity was more specific but less sensitive than AMES score to predict metastases. In conclusion, our results suggest that nm23-H1 immunostaining could be added to the classic prognostic factors currently used to predict the outcome of patients with follicular thyroid carcinoma.

Adenocarcinoma, Follicular↗

Differential influence of LDL cholesterol and triglycerides on lipoprotein(a) concentrations in diabetic patients.

OBJECTIVE: To evaluate the relationship between plasma lipid profiles and lipoprotein(a) [Lp(a)] concentrations in diabetic patients, taking into account the Lp(a) phenotype. RESEARCH DESIGN AND METHODS: We included 191 consecutive diabetic outpatients (69 type 1 and 122 type 2 diabetic patients) in a cross-sectional study Serum Lp(a) was determined by enzyme-linked immunosorbent assay, and Lp(a) phenotypes were assessed by SDS-PAGE followed by immunoblotting. The statistical methods included a stepwise multiple regression analysis using the Lp(a) serum concentration as the dependent variable. The lipid profile consisted of total cholesterol, HDL cholesterol, LDL cholesterol, corrected LDL cholesterol, triglycerides, and apolipoproteins AI and B. RESULTS: In the multiple regression analysis, LDL cholesterol (positively) and triglycerides (negatively) were independently related to the Lp(a) concentration, and they explained the 6.6 and 7.8% of the Lp(a) variation, respectively. After correcting LDL cholesterol, the two variables explained 3.8 and 6.4% of the Lp(a) variation, respectively. In addition, we observed that serum Lp(a) concentrations were significantly lower in patients with type IV hyperlipidemia (mean 1.0 mg/dl [range 0.5-17], n = 16) than in normolipidemic patients (6.5 mg/dl [0.5-33.5], n = 117) and in type II hyperlipidemic patients (IIa 15.5 mg/dl [3.5-75], n = 13; IIb 9 mg/dl [1-80], n = 45); P < 0.001 by analysis of variance. CONCLUSIONS: Lp(a) concentrations were directly correlated with LDL cholesterol and negatively correlated with triglyceride levels in diabetic patients. Therefore, our results suggest that the treatment of diabetic dyslipemia may indirectly affect Lp(a) concentrations.

Adult↗

Vitreous levels of vascular cell adhesion molecule and vascular endothelial growth factor in patients with proliferative diabetic retinopathy: a case-control study.

OBJECTIVE: To evaluate the intravitreous concentration of vascular cell adhesion molecule (VCAM)-1 in diabetic patients with proliferative diabetic retinopathy (PDR) and the relationship of VCAM-1 with vascular endothelial growth factor (VEGF). RESEARCH DESIGN AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the onset of vitrectomy from 20 diabetic patients with PDR and 20 nondiabetic control subjects with nonproliferative ocular disease. Both groups were matched by serum levels of VCGM-1 and VEGF. VCAM-1 and VEGF were determined by enzyme-linked immunosorbent assay. Statistics were determined using the Mann-Whitney U test and Spearman's rank correlation test. RESULTS: The intravitreous concentration of VCAM-1 was signifcantly elevated in diabetic patients with PDR compared with control subjects (26 ng/ml [19-118] vs. 22 ng/ml [20-47], P < 0.05). A direct correlation between VCAM-1 and total vitreous proteins was detected in diabetic patients (r = 0.64, P = 0.003), but not in control subjects. After adjusting for total intravitreous proteins, VCAM-1 was significantly lower in diabetic patients with PDR than in control subjects (8.2 ng/ml [4-31.4] vs. 43.1 ng/ml [9.7-100], P < 0.001). Intravitreous VEGF concentrations were higher in patients with PDR than in control subjects in absolute terms (1.34 ng/ml [0.16-6.22] vs. 0.009 ng/ml [0.009-0.044], P < 0.0001) and after correcting for total vitreal proteins (0.33 ng/ml [0.01-2.3] vs. 0.013 ng/ml [0.003-0.035], P = 0.0001). Finally, the vitreous ratio of VCAM-1 to proteins correlated with the vitreous ratio of VEGF to proteins in both diabetic patients (r = 0.74, P = 0.001) and control subjects (r = 0.84, P = 0.005). CONCLUSIONS: The low proportion of VCAM-1 in relation to total vitreal proteins observed in diabetic patients with PDR suggests that VCAM-1 is quenched by diabetic retina. In addition, the direct correlation detected between VCAM-1 and VEGF suggests that cellular adhesion and neovascularization may be linked processes.

Case-Control Studies↗

[Pheochromocytoma associated with multiple endocrine neoplasia 2A and sporadic: differential characteristics].

BACKGROUND: To study distinctive clinical features of pheochromocytoma in the setting of multiple endocrine neoplasia type 2A (MEN 2A) in comparison with sporadic pheochromocytoma. PATIENTS AND METHOD: All patients diagnosed of sporadic pheochromocytoma (n = 29) and in the setting of MEN 2A (n = 16) between 1976 and 1998 in a tertiary hospital were included in the study. The following variables were compared: age at diagnosis, symptoms, presence and characteristics of hypertension, size of the tumor, localization and malignancy. The accuracy of diagnostic tests was also evaluated. RESULTS: The pheochromocytoma associated to MEN 2A had a higher prevalence in our study (35.5%) and the diagnosis was performed earlier than for sporadic pheochromocytoma (29.1 [7.8] vs. 47,5 [10. 9] years; p < 0.001). Other distinctive features in comparison with sporadic pheochromocytoma were: bilaterality (81.25 vs. 3.44%; p < 0. 001), absence of symptoms (44 vs 11%; p < 0.05) and paroxysmal hypertension. Concerning the diagnostic tests, it must be noted the low sensitivity (60%) of vanillylmandelic acid in MEN 2A. CONCLUSIONS: The pheochromocytoma in the setting of MEN 2A is diagnosed at younger age and frequently asymptomatic and bilateral. In view of the high prevalence of MEN 2A in our country, a genetic analysis should be performed in all patients with pheochromocytoma, especially when it is bilateral.

Adrenal Gland Neoplasms↗

Relationship between lipoprotein(a) phenotypes and plaminogen activator inhibitor type 1 in diabetic patients.

It has been demonstrated in vitro that lipoprotein(a) [Lp(a)] increases the endothelial synthesis of plasminogen activator inhibitor 1 (PAI-1). However, this effect in vivo is controversial, and the possible relationship between PAI-1 and Lp(a) phenotypes has not been evaluated. The aim of the study was to determine the influence of Lp(a) and its phenotypes on PAI-1 serum concentrations in diabetic patients. For this purpose we include 75 Caucasian diabetic patients (34 consecutive type I and 41 consecutive type II) without late diabetic complications. Lp(a) and PAI-1 were assessed by ELISA. Lp(a) phenotypes were determined by SDS-PAGE followed by immunoblotting, and grouped according to size in small (F,B,S1,S2), big (S3,S4), and null. A linear correlation between Lp(a) and PAI-1 was not observed either as a whole or when type I and type II diabetic patients were analyzed separately. However, significant differences were detected in PAI-1 levels when Lp(a) phenotypes were considered (small: 42.1+/-31.8 ng/mL; big: 37.2+/-26.1 ng/mL; null: 14.4+/-14.4; p< 0.05). The significant differences were due to the low PAI-1 concentrations observed in patients with null phenotype. Our results suggest that fibrinolytic activity might be preserved in diabetic patients with null Lp(a) phenotype. Furthermore, it could be speculated that diabetic patients with null phenotype should be considered at low risk to develop cardiovascular disease.

Adult↗