Immunohistochemical appraisal of epithelial mesenchymal transition type III in gall bladder cancer.

Background: Epithelial-mesenchymal transition (EMT) is the heart of invasion. EMT associated with cancer progression and metastasis is known as type III EMT. Beta-catenin, E-cadherin, and MMP9 markers of EMT are routinely employed for diagnostic purposes. Aims: We employed these markers to study EMT by immunohistochemistry (IHC) in gall bladder cancer (GBC) with respect to depth of tumor invasion, clinical outcome, and disease-free survival. Settings and Design: This was a prospective case-control study. Material and Methods: Seventy gall bladders were included (50 GBC and 20 CC). After detailed histology, immunoexpression was studied in terms of percentage and strength of expression. Statistics Analysis Used: Expression was compared between CC and GBC by Student t test and analysis of variance. Kaplan-Meier was used for survival analysis, and the extent of agreement ("Kappa") was calculated. Results and Conclusions: The age of incidence of GBC was 49.40 (+11.6) years with female predominance (F:M = 4:1). In 88% (44/50) of GBC, the fundus was involved. Moderately differentiated adenocarcinoma was most frequent [54%; 27/50]. Significant downregulation of E-cadherin (P = 0.022) and beta-catenin (P < 0.001) and upregulation in MMP9 (P < 0.001) were seen in GBC with respect to CC with significant association among them. MMP9 expression was significantly associated with higher tumor stage but with chemotherapeutic response. Our results display that epithelial-mesenchymal transition type III plays a role in GBC invasion. MMP9 overexpression and loss of membranous beta-catenin may be considered a marker for poor clinical outcomes and advanced disease.

Continuous infusion of vancomycin improved therapeutic levels in term and preterm infants.

BACKGROUND: Growing evidence suggests that continuous infusion of vancomycin (CIV) is superior to intermittent infusion of vancomycin (IIV) in neonates. This quality improvement (QI) project aimed to transition from IIV to CIV with earlier and improved attainment of therapeutic vancomycin levels. METHODS: The Model for Improvement framework with Plan Do Study Act cycles was used. Prospective data were collected during three phases: IIV, CIV-1 and CIV-2. INTERVENTIONS: A QI team developed a CIV drug monograph and a multidisciplinary education package. RESULTS: Using IIV, 36% (9/25) of first vancomycin levels were within target range. CIV achieved therapeutic levels twice as quickly as IIV (p < 0.05) with improved first vancomycin target levels (IIV 36%, 9/25; CIV-1 55%, 16/29; CIV-2 61%, 14/23) and total therapeutic levels (IIV 44%, 37/84; CIV-1 56%, 55/98; CIV-2 69%, 79/114). CONCLUSIONS: This QI project demonstrated a successful transition from IIV to CIV with reduced time to achieve target vancomycin and an increased proportion of therapeutic levels.

Lactobionic acid coupled liposomes: an innovative strategy for targeting hepatocellular carcinoma.

INTRODUCTION: Liver cancer or hepatocellular carcinoma (HCC) is a major cause of death worldwide. Targeted delivery of drug to the carcinoma cell can be achieved by conjugation of ligand on the carrier system. METHODS AND MATERIALS: In this study, oxaliplatin-loaded hepatoma-targeted liposome were designed and prepared using galactosylated distearoylphosphatidylethanolamine. The liposomes were prepared by cast film method and coupled with lactobionic acid (LA-LP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a coupling agent. The coupling was confirmed by infrared spectroscopy. They were further characterized for various parameters such as vesicle shape and surface morphology, size, entrapment efficiency and in vitro release pattern. RESULTS AND DISCUSSION: The vesicle size of the uncoupled liposome (256 nm) was found to be less than LA-LP (310 nm). The uptake of LA-LP and uncoupled liposomes by BEL7402 HCC cell lines was visualized using fluorescence microscopy that revealed the dependence of liposomal recognition and higher uptake of the LA-LP. Organ distribution studies provided evidence that coupling of lactobionic acid on liposomal surface significantly enhanced the tumor uptake of drug, which is reflected by recovery of higher percentage of drug from tumor as compared to uncoupled liposomes or free drug. CONCLUSION: These studies suggest them as effective vectors for HCC targeting.

Birthweight centile charts for South Asian infants born in the UK.

BACKGROUND: UK-born infants of South Asian ethnic origin are known to have lower birthweights than their White British counterparts. When plotted on currently used birthweight charts they can be misclassified as small for gestational age. Similarly, large for gestational age infants can be missed. This has important clinical implications in their management. OBJECTIVE: To create birthweight centile charts for the UK-born South Asian infants to identify true small and large for gestational age infants. METHODS: A retrospective cross-sectional analysis of infants born 1 January 2003 to 31 December 2006 was undertaken. The birthweights of the South Asian and White British infants were compared. The LMS method was used to construct centile charts for the South Asian infants. RESULTS: 24,274 White British and 7,190 South Asian infants were included in the analysis. Overall, the South Asian males were 9-15% lighter than the White British males and the South Asian females were 9-13% lighter than the White British females. At term, the median birthweight for South Asian males was 329 g lower than that for White British males and for South Asian females 295 g less than the White British females. CONCLUSION: There are significant differences in the birthweights of White British and UK-born South Asian infants. Hence the standard birthweight centile charts which were designed using the birthweight data of White British infants appear to misclassify a proportion of South Asian infants. Use of ethnic specific birthweight charts would allow better detection of truly growth-restricted and macrosomic South Asian infants.