Human organ culture techniques for the detection and evaluation of genotoxic agents

In order to obtain information on the genotoxic metabolism of carcinogens in human skin in vivo, model in-vitro systems have been developed to mimic in-vivo metabolism qualitatively. Direct labelling (3H and 14C) and 32P-postlabelling analyses of benzo[alpha]pyrene (BP)-DNA adducts in human skin explants, CD1 mouse explants and CD1 mouse skin in vivo have thus allowed comparisons of the genotoxic metabolism of BP in mouse and human skin.     

Prostaglandins and angioplasty. An experimental study in canine arteries

To prevent platelet aggregation following percutaneous transluminal angioplasty (PTA), cyclooxygenase inhibitors such as acetylsalicylic acid (ASA) and indomethacin are recommended. However, ASA blocks both the proaggregating effects of thromboxane (TXA2) and the antiaggregating and vasodilating effects of prostacyclin (PGI2). The authors measured the contractile response of dilated canine carotid arteries in situ and in vitro using an isometric force transducer. Following PTA, contraction of the arterial wall was significantly reduced (p less than 0.01). By blocking cyclooxygenase with indomethacin (3 micrograms/ml), contraction was greatly improved (p less than 0.001). These results suggest that PTA may result in marked release of prostacyclin by the damaged arterial wall, which could account for the decreased responsiveness of the artery to exogenous norepinephrine.     

Thrombosed synthetic hemodialysis access fistulas: failure of fibrinolytic therapy

Seven episodes of acute thrombosis occurring in five patients with polytetrafluoroethylene dialysis fistulas were treated with local infusions of low-dose streptokinase. Bleeding from previous dialysis puncture sites necessitated stopping the infusion in six out of seven patients, although in one of these six, the graft reopened. The seventh patient had never been dialyzed through the graft and thrombolysis was achieved without incident. Surgery was avoided in only one patient. The authors contend that in these patients the risks of fibrinolytic therapy outweigh the benefits. Surgical thrombectomy, coupled with intraoperative angiography and possible angioplasty, is the preferred method of treating these patients. Venography prior to the creation of the fistula helps the surgeon avoid diseased vessels and may avert early failure of the fistula.