Prevalence of oral hairy leukoplakia and epithelial infection by Epstein-Barr virus in pregnant women and diabetes mellitus patients: cytopathologic and molecular study

Oral hairy leukoplakia (OHL) is generally reported in patients with severe immunosuppression, except for a few cases in individuals with moderate degree of immunodeficiency. It is a white lesion that appears mainly in the lateral border of the tongue, caused by Epstein-Barr virus (EBV). The nuclear changes caused by EBV (Cowdry A inclusion, ground glass and nuclear beading), observed in cytopathology, are specific and enough for the definitive diagnosis of OHL, independent of the identification of the virus. Here we investigated the prevalence of OHL and the presence of EBV-DNA in the lateral borders of the tongue from 90 pregnant women, 90 diabetes mellitus (DM) patients, 30 healthy individuals (negative group) and 30 HIV+ with OHL (positive group). Smears were analyzed by cytopathology and polymerase chain reaction (PCR). A case of subclinical OHL and candidiasis was identificated in a DM patient by cytopathologic analysis. PCR results demonstrated EBV-DNA in 65% of the pregnant women, in 35% of DM patients, and in 20% of the healthy individuals. We concluded that DM patients can develop OHL with a low prevalence. Furthermore, the prevalence of the EBV in lateral border of the tongue is larger in pregnant women than in healthy individuals.

Oral epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small cell lung cancer: comparative pharmacokinetics and drug-drug interactions.

The development of orally active small molecule inhibitors of the epidermal growth factor receptor (EGFR) has led to new treatment options for non-small cell lung cancer (NSCLC). Patients with activating mutations of the EGFR gene show sensitivity to, and clinical benefit from, treatment with EGFR tyrosine kinase inhibitors (EGFR-TKls). First generation reversible ATP-competitive EGFR-TKls, gefitinib and erlotinib, are effective as first, second-line or maintenance therapy. Despite initial benefit, most patients develop resistance within a year, 50-60% of cases being related to the appearance of a T790M gatekeeper mutation. Newer, irreversible EGFR-TKls - afatinib and dacomitinib - covalently bind to and inhibit multiple receptors in the ErbB family (EGFR, HER2 and HER4). These agents have been mainly evaluated for first-line treatment but also in the setting of acquired resistance to first-generation EGFR-TKls. Afatinib is the first ErbB family blocker approved for patients with NSCLC with activating EGFR mutations; dacomitinib is in late stage clinical development. Mutant-selective EGFR inhibitors (AZD9291, CO-1686, HM61713) that specifically target the T790M resistance mutation are in early development. The EGFR-TKIs differ in their spectrum of target kinases, reversibility of binding to EGFR receptor, pharmacokinetics and potential for drug-drug interactions, as discussed in this review. For the clinician, these differences are relevant in the setting of polymedicated patients with NSCLC, as well as from the perspective of innovative anticancer drug combination strategies.

Dificultats d'aprenentatge en el llenguatge oral i escrit i en matemàtiques en un cas d'un nen amb trastorn per dèficit d'atenció sense hiperactivitat

Aquest projecte final de Pràcticum I de Psicologia de l'Educació explica totes les activitats que he dut a terme al llarg de la meva estada en practiques al centre Orienta. S'hi descriuen les característiques més rellevants del centre, així com els serveis que ofereix a la comunitat educativa, molt especialment els adreçats a ajudar els infants a millorar les seves capacitats d'aprenentatge, des d'un marc teòric cognitiu-conductual i sistèmic, tot emfatitzant el treball col·laboratiu que mantenen els professionals de l'educació amb les famílies dels nens. El projecte detalla les activitats de col·laboració en la intervenció que he realitzat des de l'àmbit educatiu de la Psicologia, la seva temporització i seguiment i finalment, les conclusions i prospectiva envers el treball realitzat, així com la valoració crítica que en faig de la meva estada en pràctiques.

Assessorament per a la millora de la llengua oral en un centre de primària

Aquest projecte pretén millorar les competències en llengua oral dels alumnes a partir de la reflexió amb els mestres sobre les pràctiques que es fan servir actualment per al seu aprenentatge. A partir d'aquesta reflexió, es proposen els canvis i modificacions pertinents que podrien millorar la competència dels alumnes en llengua oral.

The Management of Patients on Oral Anticoagulation Undergoing Coronary Stent Implantation: A Survey among Interventional Cardiologists from Eight European Countries.

Purpose:  To evaluate the current management, and adherence to recommendations, of patients on oral anticoagulation (OAC) undergoing coronary stent implantation (PCI-S). Methods:  By means of a contact person who had been previously identified in 8 European countries, a questionnaire was electronically forwarded between April and July 2010 to the national institutions where PCI-S is performed. Results:  A total of  202 questionnaires (median response rate: 50%, range 33-78%) was received. The prevalence of OAC patients among those undergoing PCI-S is mostly reported 5-10% (97%). The peri-procedural pharmacological management mostly encompasses: preprocedural OAC interruption and bridging with low-molecular-weight heparin (59%), intraprocedural administration of an unfractionated heparin bolus (81%), and use of glycoprotein IIb/IIIa inhibitors on an individual basis (79%). The radial approach is reported as the preferred option (58%), as well as the implantation of bare metal stents (76%). Triple therapy (warfarin, aspirin, clopidogrel) is the most frequently prescribed (80%), generally for 1 month after bare metal stent (77%) and for at least 12 months after drug-eluting stent (60%). Throughout triple therapy, the International Normalized Ratio is mostly targeted to the lower end of the therapeutic range (77%), and gastric protection is routinely prescribed (69%), mostly by giving proton-pump inhibitors (70%). Conclusions:  Among the 202 interventional cardiologists from the 8 European countries interviewed, the management of patients on OAC undergoing PCI-S appears variable and only partially adherent to currently available recommendations. (J Interven Cardiol 2012;25:163-169).

Assessorament a un grup de treball per millora la competència oral en L2 en una escola bilingüe de Berlin

Aquest treball se centra en l'experiència teoricopràctica de l'Escola Europea Bilingüe Espanyol-Alemany Joan Miró Grundschule, en el plantejament de la millora de la competència oral en L2.

Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature

Small intestinal immunopathology following oral infection with tissue cysts of Toxoplasma gondii has been described in C57BL/6 mice. Seven days after infection, mice develop severe small intestinal necrosis and succumb to infection. The immunopathology is mediated by local overproduction of Th1-type cytokines, a so-called "cytokine storm". The immunopathogenesis of this pathology resembles that of inflammatory bowel disease in humans, i.e., Crohn's disease. In this review, we show that the development of intestinal pathology following oral ingestion of T. gondii is not limited to C57BL/6 mice, but frequently occurs in nature. Using a Pubmed search, we identified 70 publications that report the development of gastrointestinal inflammation following infection with T. gondii in 63 animal species. Of these publications, 53 reports are on accidental ingestion of T. gondii in 49 different animal species and 17 reports are on experimental infections in 19 different animal species. Thus, oral infection with T. gondii appears to cause immunopathology in a large number of animal species in addition to mice. This manuscript reviews the common features of small intestinal immunopathology in the animal kingdom and speculates on consequences of this immunopathology for humankind.

Oral cancer treatments and adherence: medication event monitoring system assessment for capecitabine

Background: Oncological treatments are traditionally administered via intravenous injection by qualified personnel. Oral formulas which are developing rapidly are preferred by patients and facilitate administration however they may increase non-adherence. In this study 4 common oral chemotherapeutics are given to 50 patients, who are still in the process of inclusion, divided into 4 groups. The aim is to evaluate adherence and offer these patients interdisciplinary support with the joint help of doctors and pharmacists. We present here the results for capecitabine. Materials and Methods: The final goal is to evaluate adhesion in 50 patients split into 4 groups according to oral treatments (letrozole/exemestane, imatinib/sunitinib, capecitabine and temozolomide) using persistence and quality of execution as parameters. These parameters are evaluated using a medication event monitoring system (MEMS®) in addition to routine oncological visits and semi-structured interviews. Patients were monitored for the entire duration of treatment up to a maximum of 1 year. Patient satisfaction was assessed at the end of the monitoring period using a standardized questionary. Results: Capecitabine group included 2 women and 8 men with a median age of 55 years (range: 36−77 years) monitored for an average duration of 100 days (range: 5-210 days). Persistence was 98% and quality of execution 95%. 5 patients underwent cyclic treatment (2 out of 3 weeks) and 5 patients continuous treatment. Toxicities higher than grade 1 were grade 2−3 hand-foot syndrome in 1 patient and grade 3 acute coronary syndrome in 1 patient both without impact on adherence. Patients were satisfied with the interviews undergone during the study (57% useful, 28% very useful, 15% useless) and successfully integrated the MEMS® in their daily lives (57% very easily, 43% easily) according to the results obtained by questionary at the end of the monitoring period. Conclusion: Persistence and quality of execution observed in our Capecitabine group of patients were excellent and better than expected compared to previously published studies. The interdisciplinary approach allowed us to better identify and help patients with toxicities to maintain adherence. Overall patients were satisfied with the global interdisciplinary follow-up. With longer follow up better evaluation of our method and its impact will be possible. Interpretation of the results of patients in the other groups of this ongoing trial will provide us information for a more detailed analysis.

Mandibular osteoradionecrosis in squamous cell carcinoma of the oral cavity and oropharynx: incidence and risk factors.

Objective. Mandibular osteoradionecrosis (ORN) is a serious complication of radiotherapy (RT) in head and neck cancer patients. The aim of this study was to analyze the incidence of and risk factors for mandibular ORN in squamous cell carcinoma (SCC) of the oral cavity and oropharynx.Study Design. Case series with chart review.Setting. University tertiary care center for head and neck oncology.Subjects and Methods. Seventy-three patients treated for stage I to IV SCC of the oral cavity and oropharynx between 2000 and 2007, with a minimum follow-up of 2 years, were included in the study. Treatment modalities included both RT with curative intent and adjuvant RT following tumor surgery. The log-rank test and Cox model were used for univariate and multivariate analyses.Results. The incidence of mandibular ORN was 40% at 5 years. Using univariate analysis, the following risk factors were identified: oral cavity tumors (P < .01), bone invasion (P < .02), any surgery prior to RT (P < .04), and bone surgery (P < .0001). By multivariate analysis, mandibular surgery proved to be the most important risk factor and the only one reaching statistical significance (P < .0002).Conclusion. Mandibular ORN is a frequent long-term complication of RT for oral cavity and oropharynx cancers. Mandibular surgery before irradiation is the only independent risk factor. These aspects must be considered when planning treatment for these tumors.

Histological and histochemical evaluation of human oral mucosa constructs developed by tissue engineering

Reconstruction of large oral mucosa defects is often challenging, since the shortage of healthy oral mucosa to replace the excised tissues is very common. In this context, tissue engineering techniques may provide a source of autologous tissues available for transplant in these patients. In this work, we developed a new model of artificial oral mucosa generated by tissue engineering using a fibrin-agarose scaffold. For that purpose, we generated primary cultures of human oral mucosa fibroblasts and keratinocytes from small biopsies of normal oral mucosa using enzymatic treatments. Then we determined the viability of the cultured cells by electron probe quantitative X-ray microanalysis, and we demonstrated that most of the cells in the primary cultures were alive and had high K/Na ratios. Once cell viability was determined, we used the cultured fibroblasts and keratinocytes to develop an artificial oral mucosa construct by using a fibrin-agarose extracellular matrix and a sequential culture technique using porous culture inserts. Histological analysis of the artificial tissues showed high similarities with normal oral mucosa controls. The epithelium of the oral substitutes had several layers, with desmosomes and apical microvilli and microplicae. Both the controls and the oral mucosa substitutes showed high suprabasal expression of cytokeratin 13 and low expression of cytokeratin 10. All these results suggest that our model of oral mucosa using fibrin-agarose scaffolds show several similarities with native human oral mucosa.

Clinicobiological progression and prognosis of oral squamous cell carcinoma in relation to the tumor invasive front: impact on prognosis

CONCLUSION: There are several factors that influence the final outcome when treating oral squamous cell carcinoma (OSCC). Invasive front phenomena and more importantly their clinicopathological translation can have a direct impact on survival, and subsequently on the decision for an adjuvant treatment. OBJECTIVES: In recent years, the concept of tumor-host interaction has been the subject of substantial efforts in cancer research. Tumoral behavior may be better understood when studying the changes occurring at the tumor-host interface. This study evaluated the influence of several clinicopathological features on the outcome of OSCCs. METHODS: The clinical records and pathology specimens of 54 patients with OSCC treated by primary resection were reviewed retrospectively. The pathologic features reviewed were: invasive front grading (IFG), stromal reaction, lymphovascular invasion (LVI), perineural invasion (PNI), margin status, and depth of invasion. RESULTS: High IFGs had a significant relationship with pT status and pN status. High IFGs were strongly correlated with nodal metastases (odds ratio (OR) = 4.77; confidence interaval (CI) = 1.37-16.64). Concerning survival, IFG had a strong impact on disease-free survival in patients treated unimodally, as did the depth of invasion in the same group. Lymphovascular involvement was found to have a negative impact on overall survival in patients treated multimodally.

Molecular mechanisms of Trypanosoma cruzi infection by oral route

Frequent reports on outbreaks of acute Chagas' disease by ingestion of food contaminated with parasites from triatomine insects illustrate the importance of this mode of transmission. Studies on oral Trypanosoma cruzi infection in mice have indicated that metacyclic trypomastigotes invade the gastric mucosal epithelium. A key molecule in this process is gp82, a stage-specific surface glycoprotein that binds to both gastric mucin and to target epithelial cells. By triggering Ca2+ signalling, gp82 promotes parasite internalisation. Gp82 is relatively resistant to peptic digestion at acidic pH, thus preserving the properties critical for oral infection. The infection process is also influenced by gp90, a metacyclic stage-specific molecule that negatively regulates the invasion process. T. cruzi strains expressing high gp90 levels invade cells poorly in vitro. However, their infectivity by oral route varies considerably due to varying susceptibilities of different gp90 isoforms to peptic digestion. Parasites expressing pepsin-susceptible gp90 become highly invasive against target cells upon contact with gastric juice. Such is the case of a T. cruzi isolate from an acute case of orally acquired Chagas' disease; the gp90 from this strain is extensively degraded upon short period of parasite permanence in the gastric milieu. If such an exacerbation of infectivity occurs in humans, it may be responsible for the severity of Chagas' disease reported in outbreaks of oral infection.

Helicobacter pylori detection in gastric biopsies, saliva and dental plaque of Brazilian dyspeptic patients

Helicobacter pylori is an important human pathogen that causes chronic gastritis and is associated with the development of peptic ulcer disease and gastric malignancies. The oral cavity has been implicated as a potential H. pylori reservoir and may therefore be involved in the reinfection of the stomach, which can sometimes occur following treatment of an H. pylori infection. The objectives of this paper were (i) to determine the presence of H. pylori in the oral cavity and (ii) to examine the relationship between oral H. pylori and subsequent gastritis. Gastric biopsies, saliva samples and dental plaques were obtained from 78 dyspeptic adults. DNA was extracted and evaluated for the presence of H. pylori using polymerase chain reaction and Southern blotting methods. Persons with gastritis were frequently positive for H. pylori in their stomachs (p < 0.0001) and there was a statistically significant correlation between the presence of H. pylori in gastric biopsies and the oral cavity (p < 0.0001). Our results suggest a relationship between gastric infection and the presence of this bacterium in the oral cavity. Despite this, H. pylori were present in the oral cavity with variable distribution between saliva and dental plaques, suggesting the existence of a reservoir for the species and a potential association with gastric reinfection.

Helicobacter pylori transiently in the mouth may participate in the transmission of infection

Helicobacter pylori infection is associated with peptic ulcer and gastric carcinoma. The oral cavity may be a reservoir for H. pylori; however, the results of studies on this subject are controversial. We employed single-step and nested polymerase chain reactions (PCR) to detect the presence of the vacA, ureA and 16S rDNA genes of H. pylori in the stomach, saliva and dental plaque of 30 subjects. The results were confirmed by sequencing. Nested 16S rDNA and ureA amplification was achieved in 80% of gastric, 30% of saliva and 20% of dental plaque specimens. Sequencing of 10, seven and four 16S rDNA products from stomach, saliva and dental plaque, respectively, showed > 99% identity with H. pylori. Sequencing of the other four oral cavity PCR products showed similarity with Campylobacter and Wolinella species. Additionally, the vacA genotype identified in the samples of different sites was the same within a given subject.H. pylori may be found in the oral cavity of patients with gastric infection, thus it could be a source of transmission. However, results obtained with detection methods based only on PCR should be interpreted with caution because other microorganisms that are phylogenetically very close to H. pylori are also present in the mouth.

Long-term efficacy and tolerability of flutamide combined with oral contraception in moderate to severe hirsutism: A 12-month, double-blind, parallel clinical trial

OBJECTIVE Our objective was to test the efficacy and tolerability of three doses of flutamide (125, 250, and 375 mg) combined with a triphasic oral contraceptive (ethynylestradiol/levonorgestrel) during 12 months to treat moderate to severe hirsutism in patients with polycystic ovary syndrome or idiopathic hirsutism. DESIGN We conducted a randomized, double-blind, placebo-controlled, parallel clinical trial. PATIENTS A total of 131 premenopausal women, suffering from moderate to severe hirsutism, were randomized to placebo or 125, 250, or 375 mg flutamide daily associated with a triphasic oral contraceptive pill. Hirsutism (Ferriman-Gallwey), acne and seborrhea (Cremoncini), and hormone serum levels were monitored at baseline and at 3 (except hormone serum levels), 6, and 12 months. Side effects and biochemical, hematological, and hepatic parameters were assessed. METHODS We used three-way ANOVA (subject, dose, and visit) with Scheffé adjustment for multiple comparisons or nonparametrical Friedman test and least-squares mean (paired data) and Kruskall-Wallis test for unpaired data analyses. We used chi(2) or Fisher's test for categorical data. RESULTS A total of 119 patients were included in the intention-to-treat analysis. All flutamide doses induced a significant decrease in hirsutism, acne, and seborrhea scores after 12 months compared with placebo without differences among dose levels. Similar related side effects were observed with placebo and 125 mg flutamide (12.5%), and slightly higher with 250 mg (17.3%) and 375 mg (21.2%). No statistically significant differences were observed either among doses or compared with placebo. CONCLUSIONS Flutamide at 125 mg daily during 12 months was the minimum effective dose to diminish hirsutism in patients with polycystic ovary syndrome or with idiopathic hirsutism.