Evaluation of antibiotic prescription in the Lebanese community: a pilot study.

BACKGROUND: Antibiotics are considered among the most commonly prescribed drug classes in developing countries. Inappropriate prescription of antibiotics is a major public health concern and is related to the development of antimicrobial resistance. OBJECTIVE: This study aimed at assessing the appropriateness of antibiotic prescription by non-infectious disease physicians in a community setting in Lebanon. METHODS: A pilot cross-sectional study was undertaken on community pharmacy patients presenting with antibiotic prescription. It was performed over a period of 4 months in different regions of Lebanon. Participants answered a questionnaire inquiring about socio-demographic characteristics, medical conditions, symptoms that required medical attention, the doctor's diagnosis, the prescribed antibiotic, and whether laboratory tests were ordered to identify the causative organism or not. Data were analyzed using SPSS 17. RESULTS: We studied 270 patients (49.3% males and 50.7% females). This study showed that the most-prescribed antibiotics were the cephalosporins (82%) and that almost half of the illnesses for which antibiotics were prescribed were respiratory tract infections (41%). The study also showed that the choice of the prescribed antibiotic was appropriate in 61.5% of the studied cases, while the prescribed dose and the duration of the treatment were inaccurate in 52 and 64% of the cases, respectively. In addition, fever seemed to be a factor that influenced the physician's prescriptions, since the choice of drug conformity to guidelines increased from 53.7% (1 day of fever) to 88.9% (1 week of fever), and the dose prescription compliance to guidelines was higher (55.9%) for patients suffering from fever compared to those with no fever (38.1%). CONCLUSION: This study showed a high prevalence of inappropriate antibiotic prescriptions in Lebanon. Therefore, actions should be taken to optimize antibiotic prescription.

Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features.

The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized that MM-associated hypoxic conditions activate EMT-related proteins and promote metastasis of MM cells. In the present study, we have shown that hypoxia activates EMT-related machinery in MM cells, decreases the expression of E-cadherin, and, consequently, decreases the adhesion of MM cells to the BM and enhances egress of MM cells to the circulation. In parallel, hypoxia increased the expression of CXCR4, consequently increasing the migration and homing of circulating MM cells to new BM niches. Further studies to manipulate hypoxia to regulate tumor dissemination as a therapeutic strategy are warranted.

The role of transforming growth factor alpha in determining growth factor independence.

Growth factor independence is a hallmark of malignancy that is attributed to the development of autocrine growth factor loops in cancer cells. However, growth factor-dependent normal cells also exhibit autocrine activity, thus raising the issue of how endogenously produced activity in cancer cells differs in a manner that leads to growth factor independence. We have examined this issue by comparing growth factor-independent HCT116 human colon carcinoma cells with a growth factor-dependent subcompartment of malignant cells designated HCT116b that was isolated from the same patient tumor. Therefore, the development of the growth factor-independent phenotype represents clonal progression within the tumor in vivo. The growth factor independence of HCT116 cells was shown to be dependent on autocrine transforming growth factor (TGF)-alpha activity, yet the isoparental HCT116b subcompartment showed similar levels of TGF-alpha expression as HCT116 when cells were in exponential growth. When both cell lines were growth arrested by nutrient deprivation, HCT116b cells required nutrient replenishment and growth factors for reinitiation of DNA synthesis, whereas HCT116 cells required only nutrient replenishment. In contrast to growth factor-dependent HCT116b cells, the HCT116 cells showed up-regulation of TGF-alpha expression during growth arrest as a result of enhanced transcription. This increased TGF-alpha expression in quiescent HCT116 cells was associated with constitutive epidermal growth factor receptor (EGFR) activation in the growth-arrested state, whereas growth-arrested HCT116b cells did not show EGFR activation. TGF-alpha antisense transfection of HCT116 cells showed that EGFR activation was due to increased TGF-alpha expression. Pretreatment of growth-arrested HCT116 cells with AG1478, a selective inhibitor of EGFR tyrosine kinase activity, blocked the reinitiation of DNA synthesis, demonstrating that growth factor independence was due to the increased TGF-alpha expression and EGFR activation of these cells in growth arrest relative to growth factor-dependent HCT116b cells. Importantly, the level of EGFR activation in growth-arrested HCT116 cells was only slightly higher than that of exponential cells, indicating that it was inappropriate EGFR activation in growth arrest rather than the amplitude of activation that generated growth factor independence.