Groshong catheter-associated subclavian venous thrombosis.

PURPOSE: To identify factors associated with the development of clinically significant venous thrombosis in cancer patients with long-term indwelling subclavian Groshong catheters (GC). Also, to assess both the subsequent performance of affected catheters and the effect of heparin and warfarin therapy on subsequent catheter function and longevity. METHODS: Longitudinal study of the outcome of clinical practice. Subset analysis of those catheters developing catheter-related venous thrombosis (CRVT). RESULTS: Thirty-seven cases of CRVT were identified in a population of 255 consecutive patients in whom a GC was inserted. Seventy percent of the thrombi occurred after an episode of previous catheter dysfunction; only 30% of the thrombi occurred de novo. An unexpectedly high risk of thrombosis was associated with insertion into the left-subclavian circulation (25 of 35 versus 135 of 220, p = 0.02) or with an antecedent episode of aspiration difficulty ("ball-valve effect" [BVE]) (20 of 35 versus 60 of 220, p < 0.01). No correlation was identified between thrombosis and tumor type, tumor histology, or preexisting medical disorders. Once identified, 79% of the involved patients received anticoagulant therapy with sequential heparin and warfarin. Overall longevity of the catheters preserved by anticoagulation (mean dwell = 202 days) far exceeded catheter longevity among the population of catheters that never developed thrombosis (mean dwell = 142 days). The mean catheter longevity after thrombosis (169 days) also exceeded the mean dwell time of all other catheters that were complication-free. CONCLUSIONS: CRVT is more likely in patients in whom the catheter is inserted in the left-subclavian circulation or who have experienced a previous episode of aspiration difficulty with the catheter (BVE). Catheter preservation with sequential heparin and warfarin therapy precludes the need for catheter removal and extends dramatically the useful life of the catheter.

Resistance to 4-(9-acridinylamino) methanesulphon-m-anisidide (m-AMSA) in human myeloid leukaemia.

Sublines of a human myeloid leukaemia cell line, KBM-3, with increasing degrees of resistance to the antileukaemic agent 4'-(9-acridinlylamino) methanesulphon-m-anisidide (m-AMSA) were evaluated for their response to this drug using a clonogenic assay to measure cell survival and alkaline elution to assess m-AMSA induced DNA strand breakage. Polyacrylamide gel electrophoresis was used to map the protein profiles of the various cell lines. The resistant lines were obtained by intermittent exposure of the KBM-3 cells to the highest tolerated concentration of m-AMSA so that the culture would be repopulated only by the most resistant subpopulation after each exposure. Two distinct phases were apparent during the development of resistance. During the first 14 months of intermittent exposure to maximally tolerated concentrations of m-AMSA, the cells developed low-degree m-AMSA resistance (5-7-fold as compared with the parent line, as measured by cell survival). This low-degree resistance was characterised by a somewhat suppressed level of DNA strand breakage and no measurable change in cellular protein levels. Subsequently, a single escalation of the m-AMSA retreatment concentration resulted in a cell population that was approximately 100-fold resistant, as assessed by cloning. This rapid phenotypic change temporally coincided with the acquisition of an almost complete refractoriness to m-AMSA-induced DNA strand breakage and the loss of a cellular 76 kDa protein. We suggest that the loss of this protein is important for the development of a highly m-AMSA resistant phenotype.