External beam irradiation as an adjunctive treatment in failing dialysis shunts.

PURPOSE: To evaluate the utility of low-dose irradiation as adjunctive treatment for failing dialysis shunts related to stenoses. MATERIALS AND METHODS: Thirty-one patients with 41 lesions in their dialysis shunts were successfully enrolled for this study. After imaging of the shunt and calculation of venous stenoses, each patient was randomized into one of two segments of the protocol: (i) angioplasty and/or stent placement alone, and (ii) angioplasty and/or stent placement followed by external beam irradiation. All patients with significant venous stenoses (> or =50%) were treated with appropriately sized PTA (percutaneous transluminal angioplasty) and Wallstents. Patients randomized to the external irradiation segment underwent localized irradiation via a Theratron cobalt unit of 7 Gy 0-24 hours and 24-48 hours after intervention. Those patients randomized to the control group received no additional treatment. Clinical follow-up included resumption of successful dialysis with appropriate hemodynamic parameters. Two follow-up shunt images were obtained, follow-up 1 (fu-1) from 90 to 179 days and follow-up 2 (fu-2) from 180 to 365 days. Percentages of significant recurrent stenoses, defined as greater than 50%, were recorded and re-treated as needed. RESULTS: Sixteen of the 31 patients underwent external beam irradiation. There were 21 lesions in the test group that underwent irradiation after intervention, and 20 lesions were treated with intervention alone. There were seven native arteriovenous fistulas and 24 Gore-tex grafts. All stenoses were either venous outflow stenoses (68%) or central stenoses (32%). The authors utilized chi2 analysis to compare restenoses rates between the control and irradiated groups at fu-1 (P<.99) and fu-2 (P<.10). CONCLUSIONS: Although the results show that external beam irradiation has minimal effects on the restenoses of dialysis grafts when used in conjunction with PTA and stent placement, further studies with a larger, more homogenous population are needed to assess the trend of improving patency rates after external beam irradiation.

Effect of modulating voltage-dependent calcium channels on cholecystokinin and acetylcholine-induced contractions of the guinea pig gallbladder.

UNLABELLED: The aim of this study was to investigate the role of extracellular Ca2+ utilization in cholecystokinin (CCK) and acetylcholine-induced guinea pig gallbladder contractions by using agents that modulate influx of extracellular Ca2+ through voltage-dependent calcium channels. METHODS: Guinea pig gallbladder muscle strips were studied isometrically at Lmax in vitro. RESULTS: (1) Acetylcholine and CCK caused dose-dependent contractions, with EDmax of 10(-4) and 10(-6) M, respectively. (2) Preventing influx of extracellular Ca2+ by incubation in Ca(2+)-free/0.1 mM EGTA solution inhibited the acetylcholine (10(-4) M)-induced contraction by 60 +/- 3% compared to only 46 +/- 5% (P < 0.05) for CCK (10(-6) M)-induced contraction. (3) Nifedipine (3 microM) inhibited the response to acetylcholine (10(-4) M) by 54 +/- 3%, compared to only 34 +/- 3% (P < 0.01) for CCK (10(-6) M). (4) Bay K 8644 (10(-7) M) significantly increased (P < 0.05) the contractile responses to low doses of each agonist: acetylcholine (10(-6) M) by 121 +/- 44% and CCK (10(-9) M) by 94 +/- 31%, but had no effect on the contraction to the EDmax of each agonist. CONCLUSIONS: These studies demonstrate: (1) acetylcholine and CCK cause guinea pig gallbladder contraction by both intracellular Ca2+ release and influx of extracellular Ca2+ through voltage-dependent calcium channels; (2) the CCK-induced contraction is more dependent on intracellular Ca2+ than is acetylcholine; and (3) acetylcholine and CCK-induced contractions can by modulated by manipulating influx of extracellular Ca2+ through voltage-dependent calcium channels.