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Objectives: In 2009-2010 a Portuguese consortium was created to implement the methodologies proposed by the Dose Datamed II (DDM2) project, aiming to collect data from diagnostic X-ray and nuclear medicine (NM) procedures, in order to determine the most frequently prescribed exams and the associated ionizing radiation doses for the Portuguese population. The current study is the continuation of this work, although it focuses only on NM exams for the years 2011 and 2012., Material and Methods: The annual frequency of each of the 28 selected NM exams and the average administered activity per procedure was obtained by means of a nationwide survey sent to the 35 NM centres in Portugal., Results: The results show a reduction of the number of cardiac exams performed in the last two years compared with 2010, leading to a reduction of the annual average effective dose of Portuguese population due to NM exams from 0.08 mSv ± 0.017 mSv/caput to 0.059 ± 0.011 mSv/caput in 2011 and 0.054 ± 0.011 mSv/caput in 2012. Portuguese total annual average collective effective dose due to medical procedures was estimated to be 625.6 ± 110.9 manSv in 2011 and 565.1 ± 117.3 manSv in 2012, a reduction in comparison with 2010 (840.3 ± 183.8 manSv)., Conclusions: The most frequent exams and the ones that contributed the most for total population dose were the cardiac and bone exams, although a decrease observed in 2011 and in 2012 was verified. The authors intend to perform this study periodically to identify trends in the annual Portuguese average effective dose and to help to raise awareness about the potential dose optimization., (Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.)

Introduction: The liver is the most important target for drug-induced toxicity. This vulnerability results from functional liver features and its role in the metabolic elimination of most drugs. Drug-induced liver injury is a significant leading cause of acute, chronic liver disease and an important safety issue when developing new drugs., Areas Covered: This review describes the advantages and limitations of hepatic cell-based models for early safety risk assessment during drug development. These models include hepatocytes cultured as monolayer, collagen-sandwich; emerging complex 3D configuration; liver-derived cell lines; stem cell-derived hepatocytes., Expert Opinion: In vitro toxicity assays performed in hepatocytes or hepatoma cell lines can potentially provide rapid and cost-effective early feedback to identify toxic candidates for compound prioritization. However, their capacity to predict hepatotoxicity depends critically on cells' functional performance. In an attempt to improve and prolong functional properties of cultured cells, different strategies to recreate the in vivo hepatocyte environment have been explored. 3D cultures, co-cultures of hepatocytes with other cell types and microfluidic devices seem highly promising for toxicological studies. Moreover, hepatocytes derived from human pluripotent stem cells are emerging cell-based systems that may provide a stable source of hepatocytes to reliably screen metabolism and toxicity of candidate compounds.

Background: Hepatocellular carcinoma (HCC) is a challenging malignancy of global importance, it is the third most common cause of cancer-related mortality worldwide. In the last years the multikinase inhibitor sorafenib has been used for advanced HCC, but some patients do not benefit from this therapy; thus, novel therapeutic options based on molecular approaches are urgently needed. microRNAs are short non coding RNAs involved in several physiological and pathological conditions including HCC and increasing evidence describes miRs as good tools for the molecular targeted therapies in HCC. The purpose of this study was to identify novel approaches to sensitize the HCC cells to sorafenib by microRNAs targeting urokinase-type plasminogen activator (uPA)., Methods: The miR-193a was validated as negative regulator of urokinase-type plasminogen activator (uPA) in 2 HCC undifferentiated cell lines by transient transfection of miR and anti-miR molecules. The molecular interaction between miR-193a and uPA mRNA target was verified by luciferase reporter assay. The miR-193a expression level was evaluated by stem-loop real time PCR in tumoral tissues from 39 HCC patients. The HCC cells were co-treated with sorafenib and miR-193a and the effects on cellular proliferation, apoptosis were tested. The effect of sorafenib on c-met expression levels was assessed by western blotting., Results: The miR-193a has resulted a negative regulator of uPA in both the HCC cell lines tested. The miR-193a expression has resulted dysregulated in tumoral tissues from 39 HCC patients. We found miR-193a down-regulation in HCC respect to peritumoral (PT) tissues and more in the cirrhotic HCCs than in non-cirrhotic ones. Transfection of HA22T/VGH HCC cells with miR-193a decreased proliferation and increased apoptosis, and combined treatment with miR-193a and sorafenib led to further proliferation inhibition., Conclusions: Our results present new advances in the post-transcriptional miR-mediated mechanisms of uPA and they suggest a new strategy to impair the aggressive behavior of HCC cells. Our findings could be helpful to explore novel approaches for multi-target and multi-agent therapies of the HCC.

The performance of magnetic nanoparticles is intimately entwined with their structure, mean size and magnetic anisotropy. Besides, ensembles offer a unique way of engineering the magnetic response by modifying the strength of the dipolar interactions between particles. Here we report on an experimental and theoretical analysis of magnetic hyperthermia, a rapidly developing technique in medical research and oncology. Experimentally, we demonstrate that single-domain cubic iron oxide particles resembling bacterial magnetosomes have superior magnetic heating efficiency compared to spherical particles of similar sizes. Monte Carlo simulations at the atomic level corroborate the larger anisotropy of the cubic particles in comparison with the spherical ones, thus evidencing the beneficial role of surface anisotropy in the improved heating power. Moreover we establish a quantitative link between the particle assembling, the interactions and the heating properties. This knowledge opens new perspectives for improved hyperthermia, an alternative to conventional cancer therapies.

Background: Frontal fibrosing alopecia (FFA) is a primary lymphocytic cicatricial alopecia with a distinctive clinical pattern of progressive frontotemporal hairline recession., Objectives: Our purpose was to describe the clinical and histopathological features as well as the response to treatment of eleven cases of FFA diagnosed at the Trichology Consultation, over three years., Methods: A retrospective case note review was performed of eleven adult patients with FFA. The clinical data as well the histopathologic findings and laboratory tests were accessed. The patients were treated with different drugs, depending on the stage of the disease. The age of onset of the alopecia ranged from 45 to 80 years. Ten patients (90.9%) were postmenopausal women. All patients had progressive and symmetrical alopecia localized to the frontal and temporal hairline. Seven patients (63.6%) had marked decreased to complete loss of eyebrows and in four patients axillar alopecia was also evident. Laboratory investigations were normal. Scalp biopsy specimens from the anterior hairline showed similar findings. No significant improvement was observed in the majority of cases., Conclusion: Differential diagnosis should take into account several other conditions. It seems there is no effective treatment proven with an appropriate level of evidence in the management of FFA.

Acute febrile illnesses comprise the majority of the human disease burden in sub-Saharan Africa. We hypothesized that arboviruses comprised a considerable proportion of undiagnosed febrile illnesses in Guinea and sought to determine the frequency of arboviral disease in two hospitals there. Using a standard case definition, 47 suspected cases were detected in approximately 4 months. Immunoglobulin M antibody capture enzyme-linked immunosorbent assays and plaque-reduction neutralization assays revealed that 63% (30/47) of patients were infected with arboviruses, including 11 West Nile, 2 yellow fever, 1 dengue, 8 chikungunya, and 5 Tahyna infections. Except for yellow fever, these are the first reported cases of human disease from these viruses in Guinea and the first reported cases of symptomatic Tahyna infection in Africa. These results strongly suggest that arboviruses circulate and are common causes of disease in Guinea. Improving surveillance and laboratory capacity for arbovirus diagnoses will be integral to understanding the burden posed by these agents in the region.

Background: Support for the role of transmembrane and membrane-proximal domains of alpha IIb beta 3 integrin in the maintenance of receptor low affinity comes from mutational studies showing that activating mutations can induce constitutive bi-directional transmembrane signaling., Design and Methods: We report the functional characterization of a mutant alpha IIb beta 3 integrin carrying the Leu718Pro mutation in the membrane-proximal region of the beta 3 cytoplasmic domain, identified in heterozygosis in a patient with a severe bleeding phenotype and defective platelet aggregation and adhesion., Results: Transiently transfected cells expressed similar levels of normal and mutant alpha IIb beta 3, but surface expression of mutant alpha v beta 3 was reduced due to its retention in intracellular compartments. Cells stably expressing mutant alpha IIb beta 3 showed constitutive binding to soluble multivalent ligands as well as spontaneous fibrinogen-dependent aggregation, but their response to DTT was markedly reduced. Fibrinogen-adherent cells exhibited a peculiar spreading phenotype with long protrusions. Immunofluorescence analysis revealed the formation of alpha IIb beta 3 clusters underneath the entire cell body and the presence of atypical high-density patches of clustered alpha IIb beta 3 containing encircled areas devoid of integrin that showed decreased affinity for the fluorescent lipid analog DiIC(16) and were disrupted in cholesterol-depleted cells., Conclusions: These findings are consistent with an important role of the membrane-proximal region of beta 3 in modulating alpha IIb beta 3 clustering and lateral redistribution of membrane lipids. Since the beta 3 mutant was associated with a thrombasthenic phenotype in a patient carrying one normal beta 3 allele, these results support a dominant role of clustering in regulating integrin alpha IIb beta 3 functions in vivo.

Megakaryocytic differentiation of myelogenous leukemia cell lines induced by a number of chemical compounds mimics, in part, the physiological process that takes place in the bone marrow in response to a variety of stimuli. We have investigated the involvement of mitogen-activated protein kinases (MAPKs) [extracellular signal-regulated protein kinase (ERK1/2) and p38] and phosphoinositide 3-kinase (PI3K) signaling pathways in the differentiated phenotypes of K562 cells promoted by phorbol 12-myristate 13-acetate, staurosporine (STA), and the p38 MAPK inhibitor SB202190. In our experimental conditions, only STA-treated cells showed the phenotype of mature megakaryocytes (MKs) including GPIbalpha expression, DNA endoreduplication, and formation of platelet-like structures. We provide evidence supporting that basal activity, but not sustained activation, of ERK1/2 is required for expression of MK surface markers. Moreover, ERK1/2 signaling is not involved in cell endomitosis. The PI3K pathway exerts dual regulatory effects on K562 cell differentiation: it is intimately connected with ERK1/2 cascade to stimulate expression of surface markers and it is also necessary, but not sufficient, for polyploidization. Finally, apoptosis and megakaryocytic differentiation exhibit different sensitivity to p38 down-regulation: it is required for expression of early specific markers but is not involved in cell apoptosis. The present work with K562 cells provides new insights into the molecular mechanisms regulating MK differentiation. The results indicate that a precise orchestration of signals, including ERK1/2 and p38 MAPKs as well as PI3K pathway, is necessary for acquisition of features of mature MKs.

The A subunit of plasma factor XIII (FXIII-A) is thought to function as an intracellular transglutaminase (TG) in the monocyte/macrophage lineage to regulate certain intracellular processes involving cytoskeleton remodeling, but its precise role and the functional consequences of its absence remain poorly understood. In the present study, we show that cellular FXIII (cFXIII) expression is largely upregulated during in vitro differentiation of monocytes into dendritic cells (DCs). Monodansyl-cadaverine, a competitive substrate of TG activity, inhibited basal and CCL19-stimulated migration of mature DCs. In agreement, FXIII-A-deficient DCs showed a reduced chemotactic response to CCL19. Consistent with these findings, CHO cells stably expressing human FXIII-A showed enhanced motility in transwell and scratch-wound assays. These cells displayed increased formation of membrane blebs, dynamic cell protrusions implicated in cell movement that were also observed in DCs. The results provide evidence suggesting that upregulation of cFXIII in DCs has a role in regulating cell motility.

Background: The A subunit of factor XIII (FXIII-A) functions as an intracellular transglutaminase (TG) in the megakaryocyte/platelet lineage, where it probably participates in the cytoskeletal remodeling associated with cell activation. However, so far, the precise role of cellular FXIII (cFXIII) and the functional consequences of its absence in FXIII-A-deficient patients are unknown., Objectives and Methods: In this study, we used platelets from four patients with congenital deficiency of FXIII-A to study the role of cFXIII in platelet functions., Results: We found that FXIII-A represents the only detectable source of TG activity in platelets and that the binding of fibrinogen in response to thrombin receptor agonist peptide (TRAP) stimulation was significantly reduced in platelets from the patients. In agreement with this, in control platelets, monodansyl-cadaverine (MDC), a competitive amino-donor for TGs, inhibited fibrinogen binding induced by TRAP in a dose-dependent manner. Moreover, upon adhesion to fibrinogen, normal platelets incubated with MDC as well as FXIII-A-deficient platelets showed a distinct extension pattern with reduced lamellipodia and increased filopodia formation, suggesting a delay in spreading., Conclusions: These findings provide evidence for the direct involvement of cFXIII-dependent TG activity in the regulation of platelet functions.

Background: The human pregnane X receptor (hPXR) is an orphan nuclear receptor that induces transcription of response elements present in steroid-inducible cytochrome P-450 gene promoters. This activation requires the participation of retinoid X receptors (RXRs), needed partners of hPXR to form heterodimers. We have investigated the expression of hPXR and RXRs in normal, premalignant, and malignant breast tissues, in order to determine whether their expression profile in localized infiltrative breast cancer is associated with an increased risk of recurrent disease., Methods: Breast samples from 99 patients including benign breast diseases, in situ and infiltrative carcinomas were processed for immunohistochemistry and Western-blot analysis., Results: Cancer cells from patients that developed recurrent disease showed a high cytoplasmic location of both hPXR isoforms. Only the infiltrative carcinomas that relapsed before 48 months showed nuclear location of hPXR isoform 2. This location was associated with the nuclear immunoexpression of RXR-alpha., Conclusion: Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator.

Glucocorticoids play a major role in attenuation of the inflammatory response and they are useful in the primary combination chemotherapy of breast cancer, since in vitro studies have demonstrated an antiproliferative effect in human breast cancer cells. In contrast, it was recently shown that glucocorticoids protect against apoptotic signals evoked by cytokines, cAMP, tumour suppressors, and death genes in mammary gland epithelia. Their actions are mediated by intracellular receptor (GR) that functions as a hormone-dependent transcription factor; however, no previous studies have been focused on GR expression in different pathologies of the human breast, and the possible relationship with that of mineralocorticoid receptor (MR) and COX-2. Also, the role of these proteins on tumoral breast epithelial cells remains unclear. Therefore, we examined GR, MR and COX-2 expression by immunohistochemistry and Western blot techniques in 142 samples of human breast obtained by total or partial mastectomy. We found that the percentage of positive patients presenting nuclear immunoreaction to GR decreased with tumor development, while all samples analyzed showed cytoplasmic immunoreactions to MR. All positive samples to COX-2 antibody showed cytoplasmic location, a higher immunoreaction being observed in benign breast diseases than in carcinomatous lesions. Thus, breast cancer progression is associated with the accumulation of GR in the cytoplasm of tumoral cells and the decrease of COX-2 expression.

15-deoxy-Delta(12,14)-prostaglandin-J(2) (15d-PGJ(2)) is a peroxisome-activated proliferator receptor-gamma (PPARgamma) agonist which contains an alpha,beta-unsaturated electrophilic ketone involved in nucleophilic addition reactions to thiols. Here we studied its effect on hypoxia-inducible factor-1alpha (HIF-1alpha) in human proximal tubular cells HK-2. 15d-PGJ(2) induced stabilization of HIF-1alpha protein, without affecting HIF-1alpha mRNA levels or proteasome activity, leading to its nuclear accumulation and activation of HIF-induced transcription. Accumulation of HIF-1alpha was unaffected by selective PPARgamma blockade nor mimicked by the PPARgamma agonists ciglitazone and 9,10-dihydro-15d-PGJ(2). N-acetylcysteine, reduced glutathione (GSH) or dithiothreitol (i.e. agents that act as thiol reducing agents and/or increase the GSH content), but not reactive oxygen species (ROS) scavengers, prevented 15d-PGJ(2)-induced HIF-1alpha accumulation whereas the inhibitor of GSH synthesis buthionine sulfoximine cooperated with 15d-PGJ(2) to accumulate HIF-1alpha. Finally, HIF-1alpha expression was increased by the electrophilic alpha,beta-unsaturated compounds acrolein and PGA(2), but not by 9,10-dihydro-15d-PGJ(2), which lacks the electrophilic cyclopentenone moiety. Taken together, these results point out to a new mechanism to increase pharmacologically the cell levels of HIF-1alpha through the electrophilic reaction of alpha,beta-unsaturated ketones with thiol groups.

Understanding the determinants of the host innate immune response to systemic administration of adenoviral (Ad) vectors is critical for clinical gene therapy. Acute toxicity occurs within minutes to hours after vector administration and is characterized by activation of innate immune responses. Our data indicate that in mice, indicators of vector toxicity include elevations of cytokine levels, liver transaminase levels and thrombocytopenia. To discern potential targets for blunting this host response, we evaluated genetic factors in the host response to systemically administered first-generation Ad vectors (FGV) and helper-dependent Ad vectors (HDV) containing beta-galactosidase expression cassettes. A preliminary screen for modulation of vector-induced thrombocytopenia revealed no role for interferon-gamma, mast cells or perforin. However, vector-induced thrombocytopenia and interleukin 6 (IL-6) expression are less evident in tumor necrosis factor alpha (TNFalpha)-deficient mice. Moreover, we also demonstrated that TNFalpha blockade via antibody or huTNFR:Fc pretreatment attenuates both thrombocytopenia (>40% increase in platelet count) and IL-6 expression (>80% reduction) without affecting interleukin 12 , liver enzymes, hematological indices or vector transduction in a murine model. Our data indicate that the use of HDV, in combination with clinically approved TNFalpha immunomodulation, may represent an approach for improving the therapeutic index of Ad gene therapy for human clinical trials.

Background: The involvement of thyroid hormones in the development and differentiation of normal breast tissue has been established. However, the association between breast cancer and these hormones is controversial. Therefore, the objective of the present study was to determine the protein expression pattern of thyroid hormone receptors in different human breast pathologies and to evaluate their possible relationship with cellular proliferation., Patients and Methods: The presence of thyroid hormone receptors was evaluated by immunohistochemistry and western blot analysis in 84 breast samples that included 12 cases of benign proliferative diseases, 20 carcinomas in situ and 52 infiltrative carcinomas., Results: TR-alpha was detected in the nuclei of epithelial cells from normal breast ducts and acini, while in any pathological type this receptor was located in the cytoplasm. However, TR-beta presented a nuclear location in benign proliferative diseases and carcinomas in situ and a cytoplasmatic location in normal breast and infiltrative carcinomas. The highest proliferation index was observed in carcinomas in situ, although in infiltrative carcinomas an inverse correlation between this index and the TR-alpha expression was encountered., Conclusions: The results of this study reveal substantial changes in the expression profile of thyroid hormone receptors suggesting a possible deregulation that could trigger breast cancer development.

Introduction: Gait and stability disorders of the elderly are frequent and a cause of disability, but studies on their clinical features and etiology are scarce, including the relationship between both disorders., Objectives: To evaluate an extensive series of patients with gait and stability disorders, its clinical variants and posible pathogenic significance., Patients and Methods: 259 patients older than 70 years consulting for chronic gait and stability symptoms in an outpatients neurologic clinic were retrospectively reviewed. Several clinical and evolution data are analyzed., Results: Mean age was 78.8 years and 61.8% were women. 52 % were hypertensive. 161 cases had disequilibrium, 91 a cautious gait and seven other types of gait abnormality. 11 % had associated dementia. 27 % showed subcortical white matter abnormalities on computed tomography scan. In 28 cases a specific cause could be established. In follow-up 33.5 % worsened. Significant differences between cases of disequilibrium and cautious gait were increased age, functional disability and turn abnormality in the latter., Conclusions: Disequilibrium and cautious gait of the elderly share some clinical features, have few specific causes and vary from mild cases to a disabling <>.

Vitamin D3 (VD) and all-trans-retinoic acid (ATRA) have been postulated as a novel treatment option for breast carcinoma. Since the combined effects of retinoids and VD derivatives are attributed to heterodimeric interactions between members of the nuclear receptor family, the expression patterns of the heterodimers formed by vitamin D3 receptor (VDR) and the retinoid receptors RARs (RAR-alpha, RAR-beta and RAR-gamma) and RXRs (RXR-alpha, RXR-beta and RXR-gamma) have been studied by immunohistochemistry in benign and malignant breast tissues. Present results revealed that immunoexpressions to all receptor types studied were higher in both in situ and infiltrative carcinomas than in benign breast diseases. In a variable number of cases of infiltrative carcinoma, immunostaining appeared in the nucleus, whereas in the other two disorders immunostaining was only cytoplasmic. The correlation established between VDR and the different isoforms of retinoid receptors revealed that VDR seems to select mainly RAR-alpha to form heterodimers and to exert their properties as transcription factor. The results of this study suggest that this heterodimer plays a critical role in cancer malignancy, and its presence indicates those patient groups presenting a better response to adjuvant therapies based on the combination of vitamin D and ATRA.

We performed a study on the expression of the PCPH protein in samples corresponding to normal, pre-malignant and malignant stages of the human mammary gland by using protocols of immunohistochemistry and Western blot analysis with anti-PCPH specific antibodies. Results obtained from the immunohistochemical study showed that PCPH was undetectable in samples of normal breast and of benign diseases, with the exception of glands presenting apocrine metaplasia, in which an intense PCPH stain was observed both in the basal cytoplasm of the secretory cells and in the apocrine secretion. On the contrary, an intense labeling was observed in the cytoplasm of neoplastic cells in samples of both ductal and lobular carcinoma in situ, with this immunostaining increasing even further in samples of infiltrating carcinoma, both ductal and lobular. Western blot analyses of the same set of samples detected a 47 kDa form as the main PCPH polypeptide present in all cases studied. However, whereas this 47 kDa polypeptide was the only PCPH form detected in normal and pre-malignant samples, multiple forms could be detected in carcinoma samples, indicating the presence of altered PCPH polypeptides at these disease stages. These results were in agreement with those from the immunohistochemical study and together indicated that PCPH protein expression represents a good molecular marker to follow the process of human breast carcinogenesis. Furthermore, these results suggested that characterization of the pattern and level of PCPH expression may be a useful tool for early identification of breast cancers.

Background: So far there have been no reports on the expression pattern of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) in human breast cells and its relationship to the estrogen receptors, ER-alpha and ER-beta, and the androgen receptor (AR)., Methods: In this study we evaluated, by immunohistochemistry and Western blot analysis, the presence and distribution of DAX-1 in benign breast disease (BBD), in situ carcinoma (CIS), and ductal and lobular breast carcinomas., Results: In BBD and breast carcinomas, DAX-1 was present in both the nuclei and the cytoplasm of epithelial cells, although in infiltrative carcinomas the percentage of nuclear immunoreaction was higher than in CIS. An important relation was observed between DAX-1 and AR expression and between this orphan receptor and nodal status., Conclusion: DAX-1 might modify the AR and ER-beta intracellular location, and because a direct positive relation between the expression of these three receptors was found it could be assumed that the presence of DAX-1 in neoplastic cells might indicate a possible failure of endocrine therapies.

Background: Our objective was to compare results of two therapeutic modalities to treat congenital aortic coarctation: intraluminal aortoplasty without endoluminal stent installation (patients in group A) vs. surgical aortic resection (patients in group B). Trans-coarctation gradient pressure was evaluated prior to and immediately after treatment. Re-coarctation, aneurysm formation, in-hospital morbidity and mortality, and complications related to treatment were also evaluated., Methods: A clinical, randomized, multicenter study was performed in pediatric patients with congenital aortic coarctation. Immediate and mid- to late therapeutic results were evaluated. With regard to statistics, we evaluated event variations by Kaplan-Meier model, nonparametric Wilcoxon test, Mann-Whitney U test, two-tailed Student t and chi-square tests, and Fisher analysis. Significance was considered relevant when p<0.05., Results: There were no differences in demographic variables, procedure failure, complications, mortality, or aortic aneurysm between groups A and B, respectively. Intraluminal angioplasty and surgical aortic resection were similarly effective in reducing trans-coarctation pressure gradient, as well as arterial systemic pressure. However, differences were found between groups A and B at follow-up. Group A showed higher re-coarctation (50 vs. 21%). Absence of peripheral arterial pulses in limbs was higher in group A (50 vs. 21%), as well as persistence of arterial hypertension (49 vs. 19%); these differences were significant (p<0.05). On the other hand, complications observed after surgical aortic resection were more serious than post-angioplasty complications, but these differences were not statistically significant., Conclusions: Although re-coarctation and persistency of arterial hypertension were less frequent after surgical aortic resection, complications observed with this procedure are more serious than complications related to angioplasty, although these differences are not statistically significant.

It is clear that survival and better outcomes after acute myocardial infarction (AMI) are dependent on rapid, complete, and sustained reperfusion of the affected myocardium. Thrombolytic therapy is currently the most common reperfusion strategy in AMI, however, a significant proportion of patients fail to reach reperfusion with this form of therapy. There is evidence from randomized trials that rescue percutaneous coronary intervention (PCI) for failed thrombolysis may convey better outcomes to patients when compared to a conservative management. Nevertheless, it is not surprising that in this inherently thrombogenic milieu, rescue PCI has a lower success rate and a high incidence of rethrombosis, which have a profoundly negative impact on the outcome of patients. Platelets are thought to play a central role in the pathophysiology of failed thrombolysis and in the thrombotic complications following PCIs. Therefore, platelet glycoprotein (GP) IIb/IIIa antagonist may be of benefit in the setting of rescue PCI. Two retrospective subgroup analyses have suggested that these potent antiplatelet agents may improve the outcome of patients undergoing rescue PCI after failed full-dose thrombolytic therapy. An increase in major bleeding, however, has also been noted. Therefore, in light of the lack of evidence deriving from randomized, placebo-controlled trials, careful consideration of several aspects relevant to this setting is needed before GP IIb/IIIa antagonists are administered in rescue percutaneous coronary procedures.

Epithelioid Hemangioendothelioma (EH) is a vascular neoplasm of soft tissue, recently described by Weiss and Enzinger. The biologic al behavior of the tumor has a intermediate malignant potential, in the sense that it has an indolent course, with the potential for recurrence, but rarely metastasizes. This tumor arises from medium- to large-sized vessels, primarily involves the soft tissues of the extremities, as well as the liver, lung, and bone, and rarely occurs in the head and neck region. Only fifteen well--documented cases of Epithelioid Hemangioendothelioma involving the head and neck region have been reported. Nine cases have been recently reported in the oral cavity. This is a report of one additional case in the tongue. Because of the intermediate malignant potential of Epithelioid Hemangioendothelioma, complete tumor resection is recommended for intraoral lesions.

Schwannomas are benign tumors of neural source produced from Schwann cells, which are the constituents and the maintenance of myelin sheath of peripheral nerves. Parapharyngeal schwannoma are sporadic and vagus nerve the one more frequently giving raise to parapharyngeal schwannoma. Those originated in sympathetic neck chain are more rare. We inform about a parapharyngeal schwannoma case of the neck sympathetic chain and perform an analyse of clinic, diagnostical, histological and therapeutical characteristics of this so infrequent pathology.

Neck emphysema is an unusual pathology in childhood depending on several conditions. We report the case of a subcutaneous emphysema of the neck after an oropharyngeal injury in a child and take the advantage of the event in order to review the etiology and pathogeny of neck emphysema, because the otolaryngologist must know the differential diagnosis, face to the presence of air inside the neck, since the definitive treatment depends on is etiology.

The great majority of parotid gland tumours are benign. Metastatic malignant ones are scarce in number. The source of these metastasis are growths localized either in head and neck or distant tumours spreading on intra- or periparotid lymph nodes. Two cases of metastatic parotid growths diagnosed and treated last year are reported. Bibliographic review of the topic.

Malignant melanomas of the oral mucous membrane seems an infrequent pathology. They are characterized by a late diagnosis, bad prognosis and a disappointing treatment, because of the difficulties encountered for its total removal owing to complicated accessibility. We report one case of mucous membrane of the mouth in a 56 year-old man, diagnosed and operated in the General Hospital of Specialties "Ciudad de Jaen". The article end with a careful revision of the literature.

It is being tumor developed from Schwann cells of peripheral nerves sheath. In its plexiform type it is a rare growth presenting solitary or in the context of von Recklinghausen's disease. The aim of this article is to present one plexiform neurofibroma localized in the parotid gland. At the same time we make a perusal on the literature of this kind of tumor.

Current fibrinolytic regimens fail to fully restore coronary blood flow in slightly less than 50% of patients with acute myocardial infarction. Platelet activation and aggregation may be responsible for a large proportion of these therapeutic failures. Therefore, platelet inhibition may enhance thrombolysis. Experimental and early clinical evidence suggest that glycoprotein IIb/IIIa antagonists may enhance reperfusion when combined with reduced doses of thrombolytic agents. However, the clinical benefit of combination therapy will depend on the outcomes of a number large clinical trials that are currently being performed.

Chronic instability is a frequent complaint in elderly patients. As literature on the subject is scarce, we investigated reversible causes, evaluating patients over 65 years of age referred to a regional neurological practice for disequilibrium lasting longer than three months. Clinical features were analyzed. Computerized tomography (CT) of the brain, and thyroid hormone and cyanocobalamin (Cc) serum levels were studied for all patients, as was clinical course. No CT abnormalities were found. Low Cc levels were observed in 6 patients, and 2 were diagnosed of previously undetected hypothyroidism. During the mean follow-up period of 12 months, improvement was seen in 3 specifically-treated patients, one with hypothyroidism and two with Cc deficit. We conclude that chronic instability in the older patient cannot usually be traced to a specific cause, but that it is important to protocolize the assessment of such patients, including routine tests for thyroid hormone and Cc levels, in order to rule out treatable causes.

The aim of this multicentered, prospective and open study was to determine the clinical and bacteriological efficacy and safety of piperacillin/tazobactam (4g/500 mg IV tid) in the treatment of 79 adult patients with complicated urinary tract infections (UTI) requiring hospitalization. Forty-seven women and 32 men (mean age 54.2 years, and range 21-91) from 4 Argentinean and 6 Mexican hospitals were enrolled. Sixty-one clinically and bacteriologically evaluable patients were treated for a mean of 9.1 days (range 5-15). A favorable clinical response was seen in 83.6% and 80% at early and late assessment, respectively. Bacteriological eradication was achieved in 85.3% and 80% at early and late estimation, respectively. Escherichia coli was isolated in 33 cases, Klebsiella pneumoniae in 8, Enterococcus spp. in 7, Proteus mirabilis in 6, Pseudomonas aeruginosa in 3, Enterobacter spp. and Morganella morganii in 2. While 21% of all the clinical isolates were resistant to piperacillin, none of them was initially resistant to piperacillin/tazobactam. However, one female patient with a persistent UTI caused by E. coli developed resistance to piperacillin/tazobactam during treatment. A 64-year-old man with frontal meningioma developed purulent meningitis due to Enterobacter cloacae after neurosurgery. He was initially treated with ciprofloxacin, rifampin and amikacin and because of persistence of fever, he was moved to piperacillin/tazobactam. After 5 days of therapy, he developed coma secondary to intracranial hemorrhage and died. By then, the platelet count was normal (220,000/microliters), but the prothrombin time (19.5 seconds) and the partial thromboplastin time (63 seconds) were significantly prolonged. Our data suggest that piperacillin/tazobactam is a reliable therapy for complicated, non-complicated, community or hospital-acquired UTI.

Oncocytoma of the salivary gland is uncommon and its histogenesis and pattern of evolution are debated. The criteria for malignancy are not well established. We report a morphologically benign oncocytoma of the parotid gland that was studied using various cell proliferation and tumor markers. These markers may have prognostic value and correlate with the aggressiveness of the tumor.