Biomedical subjects
Publications and source records attributed to M Redondo.
Two patients with a history of epistaxis who were both found to have a nasolacrimal duct melanoma are presented. A literature review revealed that no previous cases of primary nasolacrimal duct melanoma have been reported. Current therapeutic modalities are discussed.
The prostatic membrane antigen (PSMA) is a protein that is expressed in the prostatic epithelium. We studied the expression of PSMA in a series of 55 patients with different stages of prostate cancer and we compared the PSMA staining in prostate cancer cells, in high-grade prostatic intraepithelial neoplasia (PIN) and in histologically benign prostatic epithelium for the same specimen. For this purpose archival paraffin-embedded specimens were studied by immunohistochemistry with a monoclonal antibody 7E11-C5.3 against PSMA using the streptavidin-biotin method. The mean percentage of PSMA immunoreactivity was 56.67% in prostate cancer (CaP) cells, and 48.6% in PIN cells, which was significantly higher than benign-appearing prostatic epithelium (5.72%) (for each pair, p<0.001). PSMA expression was greater in CaP with a higher Gleason score (p=0.01), but no relationship was found with serum PSA value. We conclude that PSMA overexpression is detected in high-grade PIN and is associated with a higher Gleason score of prostate cancer. It is a potential marker for studying carcinogenesis and progression of prostate cancer.
The aim of this study was to identify factors related to lip cancer (LC) considering individual characteristics and sociodemographic factors. A case-control study was carried out in the province of Granada (Andalusia, southern Spain). The cases were 105 males with squamous-cell carcinoma of the lip, diagnosed between 1987 and 1989 (aged 20-70 years) and identified by means of a population-based Cancer Registry. As controls, a randomised populational sample of 239 males, stratified by age, was used. Multiple logistic regression analysis showed that risk factors are lifetime cumulative tobacco consumption and alcohol consumption. An interaction was found between alcohol consumption and the smoking habit (leaving the cigarette on the lip): OR=23.6; 95% CI: 3.9-142.0. Other risk factors identified are clear eyes (OR=3.5; CI: 95% 1.5-8.0), sun exposure early in life and cumulative sun exposure during outdoor work (OR=11.9; 95%: CI: 1.3-108.9), and skin reaction to sun exposure (Fitzpatrick levels). Another interaction was found between skin reaction and a previous history of common sporadic warts (OR=4.4; 95% CI: 1.01-19.1). We conclude that LC is related to phenotype, skin reaction to sun exposure, cumulative and early sunlight exposure, and tobacco and alcohol consumption, as well as a low educational level. Leaving the cigarette on the lip is predictive of LC risk irrespective of cumulative tobacco consumption.
OBJECTIVE: To demonstrate the usefulness of three-dimensional computed tomographic angiography (CT-3D-angiography) in the microsurgical management of aneurysms of the posterior communicating artery (PComA). MATERIALS AND METHODS: A series of 27 patients with aneurysms of the PComA diagnosed by means of CT-3D-angiography and without preoperative angiography (group A) were compared with a series of 34 cases diagnosed by cerebral angiography. The findings of the CT-3D-angiography, angiography, microsurgical exploration and clinical data were evaluated. RESULTS: A total of 75 aneurysms were diagnosed preoperatively in 66 patients and 3 additional lesions were found postoperatively in group A. The sensitivity of the CT-3D-angiography was 91.7% for diagnosis of any aneurysm with an specifity of 100%, being the snsibility of angiography a 100% and its specifity 94.9%. Mortality rate was 4.5% without differences between groups regarding clinical results or complications. Both the preoperative timing and hospitalization time were shorter in group A. CONCLUSION: The study of patients with acute subarachnoid hemorrhage with CT-3D-angiography allows a reliable diagnosis of PComA aneurysms. Moreover, provides usefull information for the microsurgical clipping. When compared with angiography in the diagnosis of PComA aneurysms, CT-3D-angiography allows to improve some health indicators with similar clinical results and complications.
Since clusterin (CLU) production in reactive astrocytes may be neuroprotective, we examined its distribution in AIDS brains where brain injury and reactive astrocytosis are common. The relative area and number of CLU-positive astrocytes, as well as their percent total of all white matter glia, significantly increased in AIDS brains with and without HIV encephalitis (P<0.05). Proliferation markers were absent. In contrast, the relative area and number of GFAP-positive astrocytes and their percent of all white matter glia, increased in some cases but the mean increases were not significant. Clusterin is sensitive marker of glial reactivity in AIDS brains and its enhanced expression was not dependent on increases in GFAP.
INTRODUCTION: Basaloid squamous carcinoma (BSC) of the head and neck is an uncommon, recently described variant of epidermoid carcinoma. BSC appears biologically with a greater propensity to local aggressiveness and metastatic potential than the conventional type. OBJECTIVES: To determine the incidence of BSC of the larynx and hypopharynx in our area, and to evaluate its behavior and prognosis. PATIENTS & METHODS: 272 cases of squamous carcinoma of the larynx and hypopharynx were reviewed and 6 diagnosis of BSC were made, corresponding to 6 tumors in 5 patients. Their clinical records were analyzed. An immunohistochemical study was performed, including antibodies against cytokeratins (CK 7, CK 8, CK 19, CK 20, CK 1, 10, 5, 14, y CK 10), epithelial markers (EMA, CEA, Ber-EP4), vimentin and three neuroendocrine markers: neuron-specific enolase, chromogranin and synaptophisin. Bcl-2 expression was also investigated. RESULTS: Most tumors were supraglottic. 5 out of 6 tumors were clinically benign, without any metastases or recurrence after exclusive surgical resection and a follow-up ranging 42 to 142 months. We detected a trend toward a primitive pattern of keratin expression. All tumors were stained with EMA and CEA MoAbs, but we could not find Ber-EP4 nor endocrine markers staining in any of them. However, BCL-2 expression was widely found in 4 out of 5 tumors immunostained. CONCLUSION: It seems to be a progressive dedifferentiation of the basaloid cell component, probably a subpopulation with more primitive features responsible of the aggressiveness reported in the literature. However, the surprising good prognosis in most of our cases makes necessary more studies and wider series to confirm our data.
Traditionally, point-of-care testing (POCT) has been used throughout the healthcare system without the involvement of the central laboratory. After an exhaustive study of the situation of these laboratories in the Costa del Sol Healthcare Area, we designed a quality control program for the POCT. This program targeted the tests done at the points of care throughout the hospital and the Primary Healthcare Area (PHA), using the Joint Commission on Accreditation of Healthcare Organisations (JCAHO) standards for waived testing. We developed two programs: hospital-based tests and ambulatory POCT for outpatients in PHA. The hospital-based POCT apparatus was used for gases, glucose, qualitative urinalysis, Helicobacter pylori detection in gastrointestinal biopsies and coagulation tests. Ambulatory POCT was used to detect glucose, qualitative urinalysis and pregnancy tests. The personnel responsible are nursing staff with no continuing training program. There was no explicit quality control program and most of the results were used as screening except for glucose in the neonatal department. Criteria for selection of kits and devices were basically based on ergonomic and economic evaluation. Therefore, we performed an evaluation of precision and accuracy of two glucose meter devices. We implemented the internal and external quality programs (IQC and EQC) for glucose testing. We elaborated a guide of standard proceedings for quantitative and qualitative POCT and created an annual course for nursing staff. The annual evaluation of the indicators showed 96% for degree of compliance with IQC; 54% of nursing staff participated in the training program; 98% of the glucometers were operating; and 88% agreement between central laboratory and POCT. As there is no previous experience in our healthcare system, this represents a promising new area of working with nurses, who show great interest in participating in these new programs.
Blood coagulation has been shown to play a role in the pathogenesis of local thrombus formation in coronary arteries. Increased plasma concentrations of thrombin activation markers such as fibrin monomers (FM) indicate coagulation activation. Therefore, we investigated FM plasma levels in 194 patients (127 nonanticoagulated and 67 anticoagulated) with stable coronary artery disease (CAD) and in 96 healthy controls. FM levels were significantly higher (P<0.0001) in nonanticoagulated patients compared with healthy controls, whereas anticoagulated patients showed significantly lower (P<0.0001) FM levels, respectively. FM levels above 0.50 mg/ml were associated with an odds ratio (OR) of 3.0 (95% confidence interval (CI), 1.7--5.5) for the presence of stable CAD in nonanticoagulated patients. However, the association lost significance after correction for possible confounders such as age, body mass index, total cholesterol, fibrinogen, sex, smoking, arterial hypertension and diabetes mellitus. In conclusion, we found elevated FM plasma levels in nonanticoagulated patients as compared with healthy controls. Elevated FM plasma levels were associated with an OR of 3.0 for the presence of stable CAD in nonanticoagulated patients.
Protein phosphorylation is involved in sperm capacitation, so the effect of protein phosphatase inhibitors on the capacitation of spermatozoa of males with unexplained infertility was investigated. d-mannose ligand specific receptor expression in fresh, living spermatozoa, capacitated or treated with calyculin A (an inhibitor of protein phosphatases 1 and 2A), was studied in three groups of men: pre-vasectomy (fertile) males, males in couples with male infertility, and males in couples with infertility of unknown aetiology. Flow cytometry showed significant differences between infertile couples with a male factor and fertile couples (P < 0.05), both after capacitation and after treatment with calyculin A. In the group of couples with infertility of unknown aetiology (n = 15), d-mannose receptor expression was diminished in six cases after classical capacitation. However, when the spermatozoa of these six men were treated with calyculin A, five showed an increased specific d-mannose receptor expression. From these results it is suggested that in vitro treatment of spermatozoa with inhibitors of protein phosphatases may be of great value in some cases of unexplained infertility.
The activity of linezolid was determined against 225 recently isolated methicillin-resistant Staphylococcus aureus (MRSA) and 20 methicillin-resistant coagulase-negative staphylococci (CoNS) with decreased levels of susceptibility to teicoplanin. Linezolid activity was compared with other new agents (quinupristin-dalfopristin, trovafloxacin, moxifloxacin, levofloxacin and telithromycin) and six other antimicrobials (erythromycin, clindamycin, gentamicin, vancomycin, teicoplanin and rifampicin). The in vitro activity of linezolid was similar to that of vancomycin. Linezolid inhibited all MRSA strains at between 0.1 and 2 mg/L and all CoNS strains tested at between 0.2 and 0.5 mg/L. These results suggest that linezolid would be useful for the treatment of infections involving these organisms.
Abnormalities of coagulation or fibrinolysis play a role in the pathogenesis of coronary artery disease (CAD). Elevated plasma levels of fibrinogen, von Willebrand factor antigen, plasminogen activator inhibitor-1 and tissue-type plasminogen activator were reported to be predictive for reinfarction and death in patients with CAD. We investigated the risk for coronary re-events associated with 18 hemostatic and fibrinolytic parameters in a prospective study including 200 survivors of myocardial infarction (MI). During a 2-year follow-up, 37 patients suffered one of the following predefined re-events: fatal MI (n = 2), non-fatal MI (n = 5), percutaneous transluminal coronary angioplasty (n = 17) or coronary artery bypass grafting (n = 13). Low plasmin-alpha2-antiplasmin complex (PAP) plasma levels were associated with an up to fivefold (95% confidence interval, 1.6-15.3) increase in relative risk. The association between decreasing PAP levels and coronary re-events remained significant (P = 0.004) after correction for possible confounders using multiple logistic regression analysis. Our data indicate low PAP plasma levels to be associated with subsequent coronary events in patients with a history of MI.
Recent reports indicate that genes with tissue-restricted expression, including those encoding the type 1 diabetes autoantigens insulin, glutamic acid decarboxylase (GAD), and the tyrosine-phosphatase-like protein IA-2 (or ICA512), are transcribed in the thymus. The reported modulation of diabetes susceptibility by genetically determined differences in thymic insulin levels and studies in transgenic mice provide correlative and functional evidence that thymic expression of peripheral proteins is crucial for immunological self-tolerance. However, there are no specific data about the existence, tissue distribution, phenotype, and function of those cells that express insulin and other self-antigens in the human thymus. We find that the human thymus harbors specialized cells synthesizing (pro)insulin, GAD, and IA-2, mainly localized in the medulla, and we demonstrate such cells also in peripheral lymphoid organs (spleen and lymph nodes). Phenotypic analysis qualifies these cells as antigen-presenting cells (APCs), including both dendritic cells and macrophages. These cells often appear surrounded by apoptotic lymphocytes, both in thymus and spleen, and may therefore be involved in the deletion of autoreactive lymphocytes. Our findings demonstrate the existence of, and define the tissue distribution and phenotype of, a novel subset of APCs expressing self-antigens in human lymphoid organs that appear to be involved in the regulation of self-tolerance throughout life.
We have analyzed the clinical, analytical, radiologic, therapeutic an evolutive of cases of systemic mastocytosis (SM) skin lesions. The diagnostic of MS is difficult in the absence of skin lesions.
The recombinant Bm86-containing vaccine Gavac(TM) against the cattle tick Boophilus microplus has proved its efficacy in a number of experiments, especially when combined with acaricides in an integrated manner. However, tick isolates such as the Argentinean strain A, show low susceptibility to this vaccine. In this paper we report on the isolation of the Bm95 gene from the B. microplus strain A, which was cloned and expressed in the yeast Pichia pastoris producing a glycosylated and particulated recombinant protein. This new antigen was effective against different tick strains in a pen trial, including the B. microplus strain A, resistant to vaccination with Bm86. A Bm95-based vaccine was used to protect cattle against tick infestations under production conditions, lowering the number of ticks on vaccinated animals and, therefore, reducing the frequency of acaricide treatments. The Bm95 antigen from strain A was able to protect against infestations with Bm86-sensitive and Bm86-resistant tick strains, thus suggesting that Bm95 could be a more universal antigen to protect cattle against infestations by B. microplus strains from different geographical areas.
Clusterin has been implicated in numerous processes including active cell death, immune regulation, cell adhesion and morphological transformation. The purpose of this study was to examine clusterin expression in a large series of breast carcinomas by immunohistochemistry and in situ hybridization. The study included 40 samples of non-neoplastic glandular epithelia, 42 benign lesions, 15 atypical intraductal hyperplasias, 35 carcinomas in situ, 114 invasive carcinomas, and lymph node metastases from 40 patients. Epithelial normal cells were always negative for clusterin expression and only 19% of the benign lesions presented positive staining. In contrast to the benign lesions, however, the frequency of clusterin positive samples increased in atypical hyperplasias (47%, P = 0.08), intraductal carcinomas (49%, P = 0.01) and invasive carcinomas (53%, P < 0.001). Positive staining presented a cytoplasmic pattern, except in 3 cases of invasive carcinomas which had nuclear staining. Clusterin mRNA by in situ hybridization confirmed the specific cellular pattern of clusterin expression by immunohistochemistry. Clusterin expression was associated with large tumor size (P = 0.04), estrogen and progesterone receptor negative status (P = 0.02 and P = 0.001, respectively) and with the progression from primary carcinoma to metastatic carcinoma in lymph nodes (80% metastatic nodes had positive expression) (P = 0.004). Ten of 15 (67%) primary carcinomas without clusterin expression became positive in lymph node metastases, while most (22 of 25, 88%) of the clusterin-positive primary carcinomas were also immunoreactive in metastases. In survival analysis, clusterin expression did not represent a prognostic indicator by uni- or multivariate analysis. The increased clusterin expression in breast carcinomas tended to correlate inversely with the apoptotic index (P = 0.09) which indicates that clusterin gene expression is not a prerequisite to cellular death by apoptosis. From these results, we suggest that clusterin may have a role in tumorigenesis and progression of human breast carcinomas.
OBJECTIVES: We sought to compare the inhibitory effects of the combination of two doses of aspirin plus clopidogrel with either drug alone on platelet aggregation and activation. BACKGROUND: Enhanced platelet inhibitory effects of clopidogrel by aspirin on platelet aggregation and activation are suggested by experimental studies but have not been shown in humans. METHODS: The effects of clopidogrel 75 mg or aspirin 100 (300) mg on platelet aggregation and activation by flow cytometry after stimulation with various agonists were determined in 30 patients with a past history of myocardial infarction. RESULTS: Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy with aspirin (24.6 +/- 3.3% or 26.6 +/- 2.7% vs. 44.7 +/- 2.9%; p < 0.001). Combined treatment significantly inhibited collagen-induced aggregation compared with aspirin and clopidogrel (16.4 +/- 2.4%, 36.5 +/- 4.2% and 59.3 +/- 5.1%, respectively;, p < 0.001) and resulted in considerable inhibition of aggregation induced by thrombin receptor agonist peptide (TRAP, p < 0.03). Clopidogrel with or without aspirin significantly suppressed expression of platelet activation markers CD 62p, CD 63 and PAC-1 after stimulation with ADP or thrombin (p < 0.001). In addition, the combined treatment was more effective than either agent alone after activation with low dose thrombin (p < 0.05). Both doses of aspirin equally potentiated the platelet inhibitory effects of clopidogrel. CONCLUSIONS In this prospective clinical ex vivo platelet study, clopidogrel was more effective than aspirin in inhibiting ADP-mediated platelet aggregation and activation. Clopidogrel in combination with aspirin showed synergistic inhibitory effects after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.
The article describes the general methods and some of the results obtained in the Psychophysiology Laboratory of the University of La Coruña. The paper covers our research on the Simon effect and accessory effect, although it is not a review of the literature. The research strategy we followed is built around the use of lateralized motor potentials recorded from scalp. These measures allow observing the way responses are selected and when they are selected, providing an invaluable tool to study response interference and to split reaction time into two halves. The research on the Simon effect concludes that interference during response selection is critical in the Simon effect but it is dubious whether this process should be considered as automatic and stimulus-driven, as is widely accepted. The experiments with the accessory effect indicate that facilitation is produced before response selection is over, which ends a long controversy about the locus of the accessory effect.
The gene coding for bovine interferon-omega1 (BoIFN-omega1) was recently cloned and expressed at high levels in the yeast Pichia pastoris. The recombinant BoIFN-omega1 protein shows antiviral activity in different cell lines and has an antiluteolytic effect in cyclic ewes. In this article, we describe a method for purification of BoIFN-omega1 expressed in the methylotrophic yeast P. pastoris and characterization of its activity in vivo. The recombinant protein secreted to the culture medium had low activity because of self-aggregation. BoIFN-omega1 was solubilized using urea and desalting and finally purified by ion exchange chromatography on Q-Sepharose Fast Flow. The yield of purified product was approximately 300 mg/L of fermentation culture, with a specific antiviral activity of 10(8) IU/mg. Its purity was at least 80%. The biologic characterization of purified BoIFN-omega1 was determined by induction of an antiviral state on ewes challenged with 100 lethal doses (LD) of Aujeszky virus and by the extension of the corpus luteum life span and interestrous interval in cyclic cows. Ewes treated with 2 x 106 IU/kg BoIFN-omega1 were protected from Aujeszky virus infection. In cows receiving an intrauterine infusion of 1 mg BoIFN-omega1, equally distributed between the two uterine horns, twice daily from day 14 to day 22 of the experimental estrous cycle, the lifespan of the corpus luteum (25 vs. 19 days) and the interestrous intervals (26 vs. 21 days) were extended when compared with a control group (p < 0.05). We show that recombinant BoIFN-omega1 purified from P. pastoris has high antiviral activity and is an effective antiluteolytic agent in cattle.