Colobomas of the optic area

A 24-year old woman displayed a coloboma of the right optic nerve with multiple small parapapillary retinochoroidal colobomas. This rare association makes one suspect that the pathogenesis of colobomatous defects of the optic disc area are caused by a faulty closure of the embryonic fissure and an abnormal maturation of the cells of the anlage of the optic nerve head.     

Difference spectrophotometric assay of nitrazepam in tablet formulations

A difference spectrophotometric procedure is described for the assay of nitrazepam in tablet formulations. The method is based on the measurement of absorbance at 282 nm of a solution of the tablet extract in 0.1 M hydrochloric acid (pH 1) relative to that of an equimolar solution in 0.1 M sodium hydroxide (pH 13). The method is precise and selective for nitrazepam in the presence of the tablet excipients and 2-amino-5-nitrobenzophenone, the principal hydrolysis product of nitrazepam. The absence of a constant isosbestic point in the difference spectrum of nitrazepam during hydrolysis in alkaline solution indicates the presence of a previously unrecognized intermediate hydrolysis product.     

Wachstumsretardierung durch A.-iliaca-Verschluss nach Herzkatheteruntersuchung

Cardiac catheterisations in newborns and infants are being performed routinely in increasing numbers for diagnostic and therapeutic purposes. Rarely, the femoral artery or the iliac artery will be completely occluded after such a procedure, and growth retardation of the lower extremity can result. We report on a case of iliofemoral artery occlusion following cardiac catheterisation in an infant. Twelve years later, a difference of 5.5 cm in leg length was noted, as well as a difference in shoe size and intermittent claudication. Following operative reconstruction, the child’s leg pain ceased. Two years after surgery, differences in leg lengths and shoe sizes are no longer significant. Vascular complications should not be underestimated despite the juvenile potential for collateral vessels. Even in the absence of signs of ischaemia, these complications necessitate further investigation and adequate treatment in due course.     

Synopsis of the workshop report and open forum

This session was chaired by Prof. R.S. Kalucy. The workshops on curriculum content and clinical training had a discussion paper available to them prepared by Dr L. Goldman.     

New potent verapamil derivatives that reverse multidrug resistance in human renal carcinoma cells and in transgenic mice expressing the human MDR1 gene.

Multidrug resistance in human renal cell carcinoma is mainly caused by expression of the MDR1 gene and is characterized by a broad spectrum cross resistance to many natural product chemotherapeutic agents. This resistance can be overcome by applying chemosensitizers which inhibit the function of the MDR1 gene product P-glycoprotein. The development of new reversing agents with fewer side effects and a higher potency in modifying resistance is a high priority of research on drug resistance. We have evaluated four new verapamil derivatives on 21 primary human renal cell carcinomas in vitro, and also tested them in an MDR-transgenic mice model. These mice express the human MDR1 gene in their bone marrow cells and measurement of their white blood counts provides a simple, rapid and reliable system to screen for the potency of MDR-reversing agents in vivo. We demonstrate here that all four drugs are effective in reversing multidrug resistance in primary cultures of human renal cell carcinomas when used in combination with vinblastine chemotherapy, and to a lesser extent with doxorubicin or daunomycin chemotherapy. Our in vivo data indicate that two of these reversing agents display low toxicity at high concentrations and are more effective at low, clinically achievable concentrations, than the other two drugs and R-verapamil. These results make the two new drugs attractive candidates to be taken into clinical trials.