Cystic cochleovestibular anomaly presenting with congenital deafness and recurrent bacterial meningitis in childhood

Recurrent bacterial meningitis (RBM) in many instances is associated with identifiable anatomical defects. Presence of congenital deafness with recurrent meningitis should alert clinician for presence of middle and inner ear malformation. These defects can be demonstrated by various neuro imaging techniques and can be surgically corrected. In this case report we describe a child seen at our institute with congenital deafness and recurrent meningitis, discuss the approach to RBM and briefly describe inner ear malformation associated with the same and how to differentiate them.     

Calcitonin receptor-stimulated migration of prostate cancer cells is mediated by urokinase receptor-integrin signaling

Abundance of calcitonin (CT) and calcitonin receptor (CTR) mRNA in primary prostate tumors positively correlates with tumor grade, and exogenously added CT increases the invasion of prostate cancer cell lines. We examined acute and chronic actions of CT on migration of highly metastatic PC-3M cells and poorly invasive LNCaP cells on several extracellular matrices in a spheroid disaggregation/migration assay. While PC-3M spheroids displayed maximum disaggregation/migration on vitronectin (VN), LNCaP spheroids preferred collagen but also migrated significantly on VN. Up-regulation of CT significantly enhanced disaggregation/migration of PC-3M spheroids on VN, but not on fibronectin. In contrast, down-regulation of CT, CTR, protein kinase A or urokinase-type plasminogen activator receptor (uPAR) led to amelioration of PC-3M spheroid disaggregation/migration. CT selectively increased surface activity of αvβ3 or α6β5 integrins in PC-3M and LNCaP cell lines, respectively, and uPAR-integrin association. Finally, either CT or urokinase could completely restore migration of CT-knock-down PC-3M spheroids. But, only forced expression of urokinase receptor coupled with exogenous addition of urokinase restored migration of CTR-knock-down spheroids. These results support our hypothesis that up-regulation of CT biosynthesis and activation of CT–CTR axis in primary prostate tumors may have direct relevance in their progression to the metastatic phenotype.     

Cost-effectiveness analysis of baclofen and chlordiazepoxide in uncomplicated alcohol-withdrawal syndrome

Objectives:

Benzodiazepines (BZDs) are the first-line drugs in alcohol-withdrawal syndrome (AWS). Baclofen, a gamma-aminobutyric acid_B (GABA_B) agonist, controls withdrawal symptoms without causing significant adverse effects. The objective of this study was to compare the cost-effectiveness of baclofen and chlordiazepoxide in the management of uncomplicated AWS.

Materials and Methods:

This was a randomized, open label, standard controlled, parallel group study of cost-effectiveness analysis (CEA) of baclofen and chlordiazepoxide in 60 participants with uncomplicated AWS. Clinical efficacy was measured by the Clinical Institute Withdrawal Assessment for alcohol (CIWA-Ar) scores. Lorazepam was used as supplement medication if withdrawal symptoms could not be controlled effectively by the study drugs alone. Both direct and indirect medical costs were considered and the CEA was analyzed in both patient''s perspective and third-party perspective.

Results:

The average cost-effectiveness ratio (ACER) in patient''s perspective of baclofen and chlordiazepoxide was Rs. 5,308.61 and Rs. 2,951.95 per symptom-free day, respectively. The ACER in third-party perspective of baclofen and chlordiazepoxide was Rs. 895.01 and Rs. 476.29 per symptom-free day, respectively. Participants on chlordiazepoxide had more number of symptom-free days when compared with the baclofen group on analysis by Mann-Whitney test (U = 253.50, P = 0.03).

Conclusion:

Both study drugs provided relief of withdrawal symptoms. Chlordiazepoxide was more cost-effective than baclofen. Baclofen was relatively less effective and more expensive than chlordiazepoxide.KEY WORDS: Alcohol-withdrawal syndrome, baclofen, chlordiazepoxide, clinical institute withdrawal assessment for alcohol, cost-effectiveness analysis