ABSTRACT
Background: Bevacizumab a recombinant humanized monoclonal antibody was approved in 2004 by US FDA for metastatic colorectal cancer. It is reported to cause potentially serious toxicities including severe hypertension, proteinuria, and congestive heart failure. Aim: To correlate adverse event tetany with the use of bevacizumab. Materials and Methods : World Health Organization's Uppsala Monitoring Centre, Sweden, for reporting of adverse drug reactions from all over the world, identified 7 cases with tetany-related symptoms to bevacizumab from four different countries. These 7 patients reported to UMC database developed adverse events described as musculoskeletal stiffness (1), muscle spasm (1), muscle cramps (1), lock jaw or jaw stiffness (4), and hypertonia (1), with hypocalcaemia. Results: After detailed study of the possible mechanism of actions of bevacizumab and factors causing tetany, it is proposed that there is a possibility of tetany by bevacizumab, which may occur by interfering with calcium metabolism. Resorption of bone through osteoclasts by affecting VEGF may interfere with calcium metabolism. Another possibility of tetany may be due to associated hypomagnesaemia, hypokalemia, or hyponatremia. Conclusions: Tetany should be considered as a one of the signs. Patient on bevacizumab should carefully watch for tetany-related symptoms and calcium and magnesium levels for their safety.
Subject(s)
Aged , Angiogenesis Inhibitors/adverse effects , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Colorectal Neoplasms/drug therapy , Female , Humans , Male , Survival Rate , Sweden , Tetany/chemically induced , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/immunologyABSTRACT
Thirty two patients with pure mitral stenosis and twenty normal subjects were studied by M-Mode Echocardiography and systolic time intervals. Preejection period (PEP) was increased in 62 percent of patients in New York Heart Association (NYHA) Class III and IV, compared to 42.9 percent of cases in NYHA class I and II. Left ventricular ejection time (LVET) was abbreviated in 87.5 percent cases in NYHA class III and IV, and in 58.3 percent of cases in NYHA class I and II. PEP/LVET ratio was significantly increased (p less than 0.01) in mitral stenosis (0.42) compared to normal subjects (0.33) while calculated left ventricular ejection fraction (EF) was significantly lower (p less than 0.01) in mitral stenosis (60%) compared to normal subjects (71.55%). It is hypothesized that a rigid "mitral complex" immobilises the posterobasal area of the left ventricle in mitral stenosis thereby impairing left ventricular contraction.