Performance of methods to assess kidney function in a predominantly overweight sample of patients with liver disease.

The assessment of glomerular filtration rate (GFR) in patients with liver disease is necessary to make decisions about organ allocation. Creatinine is widely used as a marker of GFR; however, it is not reliable in patients with liver disease. The aims of this study were to (1) determine if iodine 125-labeled iothalamate ((125)I-iothalamate) clearance calculated using the plasma decay method is equal to renal clearance of (125)I-iothalamate and (2) estimate kidney function using the creatinine-based Cockcroft-Gault and the Modification of Diet in Renal Disease equations, a cystatin C-based equation, the urine collection method for creatinine clearance, and plasma clearance of vancomycin (V) and compare these estimates to renal clearance of (125)I-iothalamate in adult patients with liver disease. Adults with liver disease received (125)I-iothalamate and V and had a catheter placed for urine collection. Blood and urine samples were collected over 8 h for analysis of (125)I-iothalamate, creatinine, and V to determine kidney function. Estimates were compared to renal (125)I-iothalamate clearance. Eight patients classified as Child-Pugh class B were enrolled: age was 52 ± 6 years; body mass index was 36.5 ± 19 kg/m(2); and Model for End-Stage Liver Disease score was 13 ± 3. Mean estimates of kidney function did not differ significantly from mean renal (125)I-iothalamate clearance (74 ± 38 mL/min/1.73 m(2)). Other methods overestimated kidney function at lower levels of GFR (<60 mL/min/1.73 m(2)) and underestimated kidney function at higher GFR levels. Given the variability in performance of methods to assess kidney function in this population, direct measurement of GFR may be preferable to indirect estimates based on marker compounds such as creatinine and cystatin C until more accurate methods are developed.

Novel tubulin polymerization inhibitors overcome multidrug resistance and reduce melanoma lung metastasis.

PURPOSE: To evaluate abilities of 2-aryl-4-benzoyl-imidazoles (ABI) to overcome multidrug resistance (MDR), define their cellular target, and assess in vivo antimelanoma efficacy. METHODS: MDR cell lines that overexpressed P-glycoprotein, MDR-associated proteins, and breast cancer resistance protein were used to evaluate ABI ability to overcome MDR. Cell cycle analysis, molecular modeling, and microtubule imaging were used to define ABI cellular target. SHO mice bearing A375 human melanoma xenograft were used to evaluate ABI in vivo antitumor activity. B16-F10/C57BL mouse melanoma lung metastasis model was used to test ABI efficacy to inhibit tumor lung metastasis. RESULTS: ABIs showed similar potency to MDR cells compared to matching parent cells. ABIs were identified to target tubulin on the colchicine binding site. After 31 days of treatment, ABI-288 dosed at 25 mg/kg inhibited melanoma tumor growth by 69%; dacarbazine at 60 mg/kg inhibited growth by 52%. ABI-274 dosed at 25 mg/kg showed better lung metastasis inhibition than dacarbazine at 60 mg/kg. CONCLUSIONS: This new class of antimitotic compounds can overcome several clinically important drug resistant mechanisms in vitro and are effective in inhibiting melanoma lung metastasis in vivo, supporting their further development.

Evaluation of zeta-potential and particle size of technetium 99mTc-sulfur colloid subsequent to the addition of lidocaine and sodium bicarbonate.

UNLABELLED: The use of (99m)Tc-sulfur colloid lymphoscintigraphy for the determination of lymph flow patterns from a tumor site and localization of the sentinel node has been widely adopted. However, the effects of multiple injections of the radiopharmaceutical can range from mild discomfort to pain. pH-adjusted lidocaine HCl coadministered with (99m)Tc-sulfur colloid presents a risk of introducing instability of the radiopharmaceutical, which could lead to aggregation, possibly impeding the kinetics of lymphatic drainage from the tumor site. METHODS: In the present study, lidocaine pH-adjusted with 4.2%, 6.3%, or 8.4% sodium bicarbonate was added to the (99m)Tc-sulfur colloid radiopharmaceutical to monitor effects on radiochemical purity, zeta-potential, particle size, and pH. These parameters were then used to evaluate the short-term stability of the preparation. RESULTS: The study revealed that the formulation of lidocaine pH-adjusted with 8.4% sodium bicarbonate added to (99m)Tc-sulfur colloid demonstrated a similar change in zeta-potential (-4.09 +/- 2.90 mV) and particle size (10-330 nm) to that of control filtered (99m)Tc-sulfur colloid (-5.09 +/- 1.68 mV and 11-343 nm, respectively). However, the 4.2% preparation showed a zeta-potential of -3.01 +/- 2.24 mV and a particle size range of 10-351 nm. The pH of the 8.4% buffered preparation, at 7.1, was closer to physiologic pH than was the control, at 6.0. The 6.3% pH-adjusted lidocaine-(99m)Tc-sulfur colloid preparation failed radiochemical purity; thus, it was not included in the analysis. CONCLUSION: Compared with other (99m)Tc-sulfur colloid test formulations of 4.2% and 6.3% pH-adjusted lidocaine, the 8.4% sodium bicarbonate pH-adjusted lidocaine-(99m)Tc-sulfur colloid preparation, taken as a whole, yielded superior quality-control parameters. This formulation would be an acceptable alternative to the control.