Hepatic duct confluence injury in blunt abdominal trauma: case report and synopsis on management

Injuries of the extra hepatic biliary tree following blunt trauma to the abdomen are rare. We present here a case of injury to the confluence of the hepatic ducts and a brief synopsis on diagnosis and management of blunt injury to the extrahepatic biliary system.     

To study voice quality before and after thyroplasty type 1 in patients with symptomatic unilateral vocal cord paralysis

PURPOSE: The purpose of this study was to evaluate voice quality before and after thyroplasty type 1 in patients with symptomatic unilateral vocal cord paralysis. METHODS: Fifteen consecutive cases of unilateral symptomatic vocal cord paralysis of a known or idiopathic etiology with the duration of 6 months who have failed conventional speech therapy. The voice quality was assessed by perceptual evaluation, acoustic measures, and aerodynamic measures. The position of the cord was assessed by using fiberoptic laryngoscope. The procedure was done under local anesthesia. RESULTS: Among 15 patients, on the first postoperative day, 7 patients were changed to moderate dysphonia and 8 patients had a near-normal voice. On the 30th postoperative day, 3 patients had persistent moderate dysphonia, nine patients had near-normal voice, and 3 patients had normal voice. CONCLUSION: Thyroplasty type 1 successfully reduces glottic gap and improves voice quality in patients with unilateral vocal cord paralysis. Improved maximum phonation time, signal-to-noise ratio, shimmer, jitter, fundamental frequency, and intensity of voice appear to be directly related to medialization of the paralyzed vocal cord.     

Serial blood lactate levels as a predictor of mortality in children after cardiopulmonary bypass surgery.

OBJECTIVE: To assess the role of serial lactate levels in determining outcome after cardiopulmonary bypass surgery in children. DESIGN: Analysis of retrospectively collected data. SETTING: Cardiac intensive care unit of a tertiary care children's hospital. PATIENTS: Patients were 129 children who underwent surgery for congenital cardiac defects. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Patients were categorized for disease severity using the Risk Adjustment for Congenital Heart Surgery method. Blood lactate levels were obtained at admission to the cardiac intensive care unit and then serially until they were <2 mmol/L. Lactime, time during which the lactate remains >2 mmol/L, was noted for each patient. The primary outcome measured was mortality. Secondary outcomes measured were ventilator days and hospital days. Six patients died, and of these five were neonates. Nonsurvivors had higher initial postoperative lactate concentration (p = .01), peak postoperative lactate concentration (p = .003), and lactime (p = .05). In binomial logistic regression analysis, lactime was the strongest predictor of mortality (p = .03). The positive predictive value for all age groups was highest for lactime >48 hrs, with a positive predictive value of 60%, and among the neonates it was 75%. Initial lactate level >6 mmol/L had a positive predictive value of only 6%, and the peak lactate level >6 mmol/L had a positive predictive value of only 15%. Lactime also had a significant association with ventilator days and hospital days among the survivors (p = .001). CONCLUSIONS: Lactime was a useful predictor of mortality in children undergoing repair or palliation of congenital cardiac defects under cardiopulmonary bypass. Initial and peak lactate levels had a poor positive predictive value for mortality. Lactime also was associated with the number of ventilator days and hospital days in those who survived.     

Activation of caspase-9 with irradiation inhibits invasion and angiogenesis in SNB19 human glioma cells

Glioblastoma multiforme, the most common brain tumor, typically exhibits markedly increased angiogenesis, which is crucial for tumor growth and invasion. Antiangiogenic strategies based on disruption of the tumor microvasculature have proven effective for the treatment of experimental brain tumors. Here, we have overexpressed human caspase-9 by stable transfection in the SNB19 glioblastoma cell line, which normally expresses low levels of caspase-9. Our studies revealed that overexpression of caspase-9 coupled with radiation has a synergistic effect on the inhibition of glioma invasion as demonstrated by Matrigel assay (> 65%). Furthermore, sense caspase stable clones cocultured with fetal rat brain aggregates along with radiation showed complete inhibition as compared to the parental and vector controls. During in vitro angiogenesis, SNB19 cells cocultured with human microvascular endothelial cells (HMEC) showed vascular network formation after 48-72 h. In contrast, these capillary-like structures were inhibited when HMEC cells were cocultured with sense caspase stable SNB19 cells. This effect was further enhanced by radiation (5 Gy). Signaling mechanisms revealed that apoptosis is induced by cleavage of caspase-9 by radiation, loss of mitochondrial membrane potential and activation of caspase-3. These results demonstrate that activation of caspase-9 disrupts glioma cell invasion and angiogenesis in vitro. Hence, overexpression of proapoptotic molecules such as caspase-9 may be an important determinant of the therapeutic effect of radiation in cancer therapy.     

Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy

We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy.     

Inhibition of cathepsin B and MMP-9 gene expression in glioblastoma cell line via RNA interference reduces tumor cell invasion, tumor growth and angiogenesis

Extracellular proteases have been shown to cooperatively influence matrix degradation and tumor cell invasion through proteolytic cascades, with individual proteases having distinct roles in tumor growth, invasion, migration and angiogenesis. Matrix metalloproteases (MMP)-9 and cathepsin B have been shown to participate in the processes of tumor growth, vascularization and invasion of gliomas. In the present study, we used a cytomegalovirus promoter-driven DNA template approach to induce hairpin RNA (hpRNA)-triggered RNA interference (RNAi) to block MMP-9 and cathepsin B gene expression with a single construct. Transfection of a plasmid vector-expressing double-stranded RNA (dsRNA) for MMP-9 and cathepsin B significantly inhibited MMP-9 and cathepsin B expression and reduced the invasive behavior of SNB19, glioblastoma cell line in Matrigel and spheroid invasion models. Downregulation of MMP-9 and cathepsin B using RNAi in SNB19 cells reduced cell-cell interaction of human microvascular endothelial cells, resulting in the disruption of capillary network formation in both in vitro and in vivo models. Direct intratumoral injections of plasmid DNA expressing hpRNA for MMP-9 and cathepsin B significantly inhibited established glioma tumor growth and invasion in intracranial tumors in vivo. Further intraperitoneal (i.p.) injections of plasmid DNA expressing hpRNA for MMP-9 and cathepsin B completely regressed pre-established tumors for a long time (4 months) without any indication of these tumor cells. For the first time, these observations demonstrate that the simultaneous RNAi-mediated targeting of MMP-9 and cathepsin B has potential application for the treatment of human gliomas.     

Sinonasal epithelial-Myoepithelial carcinoma-A rare entity

Epithelial-myoepithelial carcinoma is a rare salivary gland tumor. It comprises less than 1% of all salivary gland tumors. It generally arises from the parotid gland. Unusual sites of occurrence include sinonasal tract, lung, trachea, lacrimal gland and breast. Histopathologically epithelial-myoepithelial carcinoma comprises a dual population of ductal and myoepithelial cells. We report an extremely rare case of epithelial-myoepithelial carcinoma occurring in the sinonasal tract of young man.     

Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics

The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases, ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 [1]. This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors.