In vitro primary cell culture as a physiologically relevant method for preclinical testing of human oncolytic adenovirus.

Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.

Flexor tenolysis in children.

This study aimed to determine whether there is an age below which flexor tenolysis may not be beneficial and whether there is any detriment to waiting for a more appropriate age. In this study, patients in their first decade had minimal improvement in their active flexion after flexor tenolysis. Six patients were tenolysed more than 1 year after their original operation and none appeared to have been compromised by the prolonged interval between injury repair and tenolysis. Significant improvement in active flexion after tenolysis can be confidently expected only in children over 11 years old.

Dorsal ganglion of the wrist--pathogenesis and biomechanics. Operative v. conservative treatment.

It is shown that the dorsal ganglion arises as a herniation from the dorsal scapholunate ligament. This herniation increases in size (according to La Place's law) owing to the unidirectional pinchcock effect of the mucosal folds of the duct and the pressure of the overlying extensor retinaculum until the distending pressure inside the ganglion equals the overlying tissue pressure. Wrist gangliography, retrograde wrist arthrography, histology and nuclear magnetic resonance were used to prove this conclusively. Bearing the pathogenesis in mind, the best clinical results were obtained by excision of the ganglion with 0.5 cm2 of dorsal scapholunate ligament and closure of the dorsal capsule with a 3/0 Vicryl purse-string suture. Non-surgical sclerotherapy led to severe inflammation and sepsis and a recurrence rate of 45%. Conservative therapy is illogical since the communicating duct remains and synovial fluid from the scapholunate joint will cause a reherniation and recurrence of the ganglion.

Significance of assault injury of the hand. A case report.

A patient who developed septic arthritis of a metacarpophalangeal joint after penetration by a tooth in a fist fight is described. The importance of recognising such a lesion at the time of injury is stressed.

Phaeochromocytoma as a cause of pulmonary oedema.

Phaeochromocytoma can mimic many serious disease entities. This report describes a 43-year-old man who presented with pulmonary oedema due to a phaeochromocytoma. Predominantly adrenaline-secreting tumours seem to predispose to this complication. Labetalol, a combined alpha- and beta-receptor blocker, should be considered as the initial treatment in these cases and continued during surgery.