Differential expression of miR‐21, miR‐125b and miR‐191 in breast cancer tissue

Aims: To develop new biomarkers for early detection and to inform effective clinical management of breast cancer. Methods: Real‐time polymerase chain reaction was used to profile microRNA (miRNA) in tumor tissue from 50 breast cancer patients using non‐tumor breast tissue from each patient as a control. We have focussed on three miRNA; miR‐21, miR‐125b and miR‐191, all of which have been implicated in breast cancer with either proven or predicted target genes involved in critical cancer‐associated cellular pathways. Results: Upregulation of miR‐21 and miR‐191 and downregulation of miR‐125b, was found in breast cancer tissue. Combined expression analysis of miR‐125b/miR‐191 increased sensitivity to 100% and specificity to 94% while miR‐21/miR‐191 increased to 92% and 100%, respectively. Therefore, combination of two miRNA gives a better prediction than individual miRNA. Conclusions: We could differentiate between breast cancer and adjacent non‐tumor breast tissue as a control with a high degree of sensitivity and specificity in the Mexican population using a combined expression analysis of only two miRNA. These observations, although a proof of principle finding at this time, show that a combined expression profile of two miRNA (miR‐125b/miR‐191 and miR‐21/miR‐191) can discriminate between breast cancer and non‐tumor tissue with high specificity and sensitivity.     

Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial.

PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival. CONCLUSION: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.     

The Impact of Personality Disorders and Severity of Dependence in Psychosocial Problems

The comorbidity between Personality Disorders and Substance Use Disorders is well documented. Relationships between these two mental disorders are complex, and their concomitance generates poorer therapeutic prognosis and more severe psychosocial problems than either disorder alone. The purpose of this study was to compare three models of the relationship between personality disorders, substance use disorders and substance-related problems. Substance use disorder patients (n = 199) were recruited from outpatient centers for drug abuse care. The International Personality Disorder Examination Screening Questionnaire, European Addiction Severity Index and Substance Dependence Severity Scale were administered. For statistical analysis, t test, Pearson correlations and structural equation models were used. Patients with comorbidity showed more severe substance use disorder and more substance-related problems than patients without comorbidity. The three models fit well to the data, but two model with the effect mediation of severity of substance dependence between personality disorders and substance-related problems explained more variance observed. Considering the impact of personality disorders on family/social functioning, legal status and employment in these patients, integrated treatment models are needed to provide efficient care.     

Defining functional dyspepsia

Dyspepsia and functional dyspepsia represent a highly significant public health issue. A good definition of dyspepsia is key for helping us to better approach symptoms, decision making, and therapy indications.During the last few years many attempts were made at establishing a definition of dyspepsia. Results were little successful on most occasions, and clear discrepancies arose on whether symptoms should be associated with digestion, which types of symptoms were to be included, which anatomic location should symptoms have, etc.The Rome III Committee defined dyspepsia as "a symptom or set of symptoms that most physicians consider to originate from the gastroduodenal area", including the following: postprandial heaviness, early satiety, and epigastric pain or burning. Two new entities were defined: a) food-induced dyspeptic symptoms (postprandial distress syndrome); and b) epigastric pain (epigastric pain syndrome). These and other definitions have shown both strengths and weaknesses. At times they have been much too complex, at times much too simple; furthermore, they have commonly erred on the side of being inaccurate and impractical. On the other hand, some (the most recent ones) are difficult to translate into the Spanish language. In a meeting of gastroenterologists with a special interest in digestive functional disorders, the various aspects of dyspepsia definition were discussed and put to the vote, and the following conclusions were arrived at: dyspepsia is defined as a set of symptoms, either related or unrelated to food ingestion, localized on the upper half of the abdomen. They include: a) epigastric discomfort (as a category of severity) or pain; b) postprandial heaviness; and c) early satiety. Associated complaints include: nausea, belching, bloating, and epigastric burn (heartburn). All these must be scored according to severity and frequency. Furthermore, psychological factors may be involved in the origin of functional dyspepsia. On the other hand, it has proven very difficult to establish a clear correlation between symptoms and pathophysiological mechanisms.     

Transfer and adsorption of 1-pyrene sulfonate at the water ∣ 1,2-dichloroethane interface studied by potential modulated fluorescence spectroscopy

The transfer mechanism of 1-pyrene sulfonate anion (PSA^?) across the polarized water ∣ 1,2-dichloroethane (DCE) interface was investigated by a combination of electrochemical techniques and potential modulated fluorescence (PMF) spectroscopy under total internal-reflection. The dependence of the cyclic voltammogram and the ac voltammogram on the PSA^? concentration showed an apparent reversible ion transfer process. However, the PMF responses exhibited a complex dependence on the PSA^? concentration, revealing adsorption and dimerization processes taking place at the interface. Analysis of the dynamic spectroelectrochemical responses suggests that PSA^? is adsorbed at the interface prior to the transfer step. Upon transferring to the organic phase, PSA^? appears to accumulate at the interface undergoing a dimerization reaction.     

Sequential Organ Failure Assessment (SOFA) scores differ between genders in a sepsis cohort: Cause or effect?

Background.

Controversy exists regarding the influence of gender on sepsis events and outcome. Epidemiological data from other countries may not always apply to local circumstances. The aim of this study was to identify gender differences in patient characteristics, treatment, and outcome related to the occurrence of sepsis at admission to the ICU.

Methods.

A prospective observational cohort study on patients admitted to the ICU over a 3-year period fulfilling sepsis criteria during the first 24 hours. Demographic data, APACHE II score, SOFA score, TISS 76, aetiology, length of stay (LOS), mortality rate, and aspects of treatment were collected and then analysed with respect to gender differences.

Results.

There were no gender-related differences in mortality or length of stay. Early organ dysfunction assessed as SOFA score at admission was a stronger risk factor for hospital mortality for women than for men. This discrepancy was mainly associated with the coagulation sub-score. CRP levels differed between genders in relation to hospital mortality. Infection from the abdominopelvic region was more common among women, whereas infection from skin or skin structures were more common in men.

Conclusion.

In this cohort, gender was not associated with increased mortality during a 2-year follow-up period. SOFA score at ICU admission was a stronger risk factor for hospital mortality for women than for men. The discrepancy was mainly related to the coagulation SOFA sub-score. Together with differences in CRP levels this may suggest differences in inflammatory response patterns between genders.     

Extranodal Hodgkin disease: spectrum of disease.

Extranodal lesions in Hodgkin disease may develop and spread to virtually any organ system, simulating other neoplastic or infectious diseases. It is important to determine whether extranodal involvement represents a primary manifestation or dissemination of systemic disease, which has a poorer prognosis. Computed tomography (CT) is the preferred modality, although ultrasonography and magnetic resonance (MR) imaging may also be helpful. CT is superior to conventional radiography in assessing chest disease, although MR imaging is more sensitive than CT in detecting chest wall involvement. CT is preferred for evaluating hepatic lymphoma and has proved particularly valuable in diagnosing gastric lymphoma and detecting renal or perirenal masses. CT and MR imaging are equally effective in detecting brain Hodgkin disease; however, the latter is superior in the detection of extracerebral tumor deposits in the subdural or epidural space. MR imaging is also preferred for evaluating meningeal and spinal cord involvement. Both MR imaging and CT allow excellent assessment of bone texture and accurate analysis of tumoral bone invasion, but MR imaging is superior in demonstrating bone marrow infiltration, and CT is superior in delineating the extent of cortical bone destruction. In the future, metabolic positron emission tomography may provide more information about extranodal lymphoma than do the current imaging modalities.