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Comparison of Cystine Solvents
Calculi 744
745
NUCLE:ATION KINtTICS OF CALCIUM OXALATE. Birdwell Finlayson, M.D., Ph.D., Gainesville, Florida. (Presentation to be made by Dr. Finlayson) In closed systems, on a 37°c shaker bath, nucleation lag times (1) were measured as function of initial relative supersaturation (RS) and shaker frequency. RS was calculated with Equil and twas taken to be the time to first visible turbidity. Using Volmer-~eckeE 2Doring nucleation theory, i.e., J=Bexp[-A(o )/r ](ln RS) with A and B constants, a surface energy,a~Rd T the absolute tempeEfture and the usual assumption that nucleation rate (J)=, , the r~tio (o /T) was c:btained by plotting ln(l/1 ) vs ln- (RS). agglow ~n RS inital of 35 without agitation O was 30 erg/cm. We have e 2timated a for homogeneousaR8cleation to be 67-69 erg/cm suggesting that heterogeneous nucleation predaninates in our systems. Several models have been defined which can be tested. According to nucle3tion theory, the 2pherical cap model gives R = ( 0 /a) =(2+cose)(l-cose) /4 which suggests the calcium oxal~e~ heterogeneous catalytic surface contact angle, e, is 50.26°. At the time of this writing, we are also evaluating the model "nucleation around a foreign mote." The analysis will yield the mote radius, r , and the liquid- s~strate surface energy, ors· The mo8el is ln(lh) = Aln RS+B(r )lnRS+c(r ,015 ). r3 and Care evaluated by insistin8 that a p£ot of the righthand side of (1) vs the lefthand side of (1) is linear. Evaluation of Band C for r and aI.S should reveal whether physically meaningful interf\retations can be made. Increasing the frequency of the shaker gives an apparent increase in effective temperature. A plot of (o/r) vs shaker frequency shows the plateau described by Muf££n and others for other salts.
COMPARISON OF CYSTINE SOLVENTS. Mitchell Wiatrak and L. Paul Sonda, 111, Ann Arbor, Ml (Presentation to be made by Dr. Sanda) Despite the recent advances in extracorporeal shock wave 1 ithotripsy (ESWL), cystine stones remain difficult to treat. These stones are difficult to fragment by ESWL, but can be dissolved using a variety of chemical methods. We have evaluated various techniques of chemical dissolution of cysteine using nephelometry, a simple but reliable technique that measures the intensity of monochromatic I ight scattered by a suspension. Our initial testing of this method showed a 1 inear relationship between cysteine concentration and light transmittance in the range of 2-6 mg/ml. The effect of pH on cysteine dissolution was also evaluated. The following solutions were tested: 8.4% bicarbonate (pH 10,7), 5% alpha-mercaptopropionylglycine in carbonate solution (pH 8.0), ),5% d-penicillamine in carbonate solution (pH 8, 10, and 11), 2% acetylcysteine in carbonate solution solution (pH 8, 10, and 11), and 2% acetylcysteine in 8.4% bicarbonate (pH 8). At pH 8.0, acetylcysteine was the most effective agent in
746
747
THR ROLP OP CHEMOLYSIS IN STONE MANAGEMENT. Stephen r. Dretl,:, Boston, MA (Presentation to be made by Dr. Dretler) with the emergence of ESWL and percutaneous ultrasonic lithotripsy (PUL), little attention has been paid to the usefulness of chemolysis. There are many clinical circumstances when cl,emolysis is invaluable for completing stone
RED CELL OXALATE FLUX IN PATIENTS UNDERGOING ESWL. Mani Menon, Worcester, Ma., *Robert A. Roth, Burlington, Ma., *Paul ~ Lee and*Tadeusz Strzelecki, Worcester, Ma. (Presented by Dr. Menon) We have shown that renal cortical mitochondria have a carrier system for the transport of oxalate (J.Biol .Chem. In Press) and that a decrease in transmembrane oxalate transport is the primary biochemical abnormality seen in one experimental mod~] of nephrolithiasis (J.Urol. 135:234A, 1986). Baggio et al have recently demonstrated that an alteration in red cell oxalate flux is present in a substantial proportion of patients with nephrolithiasis (N. Engl .J.Med. 314:599, 1986) and have hypothesized that this abnormality is an indicator of alterations in the transport of oxalate by renal cellular membranes. In order to characterize the changes in red cell oxalate flux that occur in nephrolithiasis, we have begun an evaluation of oxalate transport in patients undergoing ESWL. Oxalate fluxes were measured as previously described by Baggio and collegue1. Thirty subjects with no family or personal hi~tory of nephrolithiasis and 200 patients with renal stones form the study population. The measurement bf oxa 1ate trans port is performed by an investigator unaware of the clinical history and the code will be broken upon accrual of the designated number of study patients. The rate of oxalate transport will be correlated with the chemical composition of the renal stone, the volume of the stone burden, the metabolic activity of stone formation and, where possible, urinary and serum parameters conventionally measured in urolithiasis.
treatment:
for
large struvite calculi,infusion
of Renacidin after ESWL or PUL will both complGte stone therapy and decrease recurrence rates; dissolution of struvite fragments caught distal to a narrow but not totally obstructing infunclibulum; as a nonoperative method for successful manarJement of struvite "steinstrasse"
in patients with ileal and non-refluxing colon conduits; and for dissolvin9 struvite calculi transplanted kidneys. Uric acid calculi may be difficult to visualize during FSW~, even
with contrast.
in
If post ESWL ultrasound does not
demonstrate all uric acid fragments are small
enouyh to pass, Tromethamine-E (THA~-R) or NAf!C03 irrigation is used percutaneously or via ureteral catheter.
Uric acid ''Steinstrasse''
may be treated by PCN and THAM-E or NAHC03 irrigation. Cystine fragments left after PUL or ES\.'VL may be treated by TIIAM-E or Acetylcyst.ine chemolysis. DRG's for stone disease should not he so etched in stone as to financially prohibit the application of chemolysis for appropriate circumstances.
dissolving reagent grade cysteine.
However, in the more
alkaline range all the solutions had a similar effect which was superior to that seen at lower pH. The nephelometry data using reagent grade cysteine was compared to direct irrigation of cystine calculi removed from a patient via percutaneous extraction.
The rates of dissolution for
the various solutions were quite comparable to that seen with nephelometry suggesting that reagent grade cystine, which is readily avaj lab le and inexpensive, may be a useful model for further stuides to evaluate other methods to enhance the rate of the chemical dissolution of cystine stones. The carbonate solution that we developed appears to be an inexpensive, new solvent that is superior to currently recommended methods.
290A
745
NUCLE:ATION KINtTICS OF CALCIUM OXALATE. Birdwell Finlayson, M.D., Ph.D., Gainesville, Florida. (Presentation to be made by Dr. Finlayson) In closed systems, on a 37°c shaker bath, nucleation lag times (1) were measured as function of initial relative supersaturation (RS) and shaker frequency. RS was calculated with Equil and twas taken to be the time to first visible turbidity. Using Volmer-~eckeE 2Doring nucleation theory, i.e., J=Bexp[-A(o )/r ](ln RS) with A and B constants, a surface energy,a~Rd T the absolute tempeEfture and the usual assumption that nucleation rate (J)=, , the r~tio (o /T) was c:btained by plotting ln(l/1 ) vs ln- (RS). agglow ~n RS inital of 35 without agitation O was 30 erg/cm. We have e 2timated a for homogeneousaR8cleation to be 67-69 erg/cm suggesting that heterogeneous nucleation predaninates in our systems. Several models have been defined which can be tested. According to nucle3tion theory, the 2pherical cap model gives R = ( 0 /a) =(2+cose)(l-cose) /4 which suggests the calcium oxal~e~ heterogeneous catalytic surface contact angle, e, is 50.26°. At the time of this writing, we are also evaluating the model "nucleation around a foreign mote." The analysis will yield the mote radius, r , and the liquid- s~strate surface energy, ors· The mo8el is ln(lh) = Aln RS+B(r )lnRS+c(r ,015 ). r3 and Care evaluated by insistin8 that a p£ot of the righthand side of (1) vs the lefthand side of (1) is linear. Evaluation of Band C for r and aI.S should reveal whether physically meaningful interf\retations can be made. Increasing the frequency of the shaker gives an apparent increase in effective temperature. A plot of (o/r) vs shaker frequency shows the plateau described by Muf££n and others for other salts.
COMPARISON OF CYSTINE SOLVENTS. Mitchell Wiatrak and L. Paul Sonda, 111, Ann Arbor, Ml (Presentation to be made by Dr. Sanda) Despite the recent advances in extracorporeal shock wave 1 ithotripsy (ESWL), cystine stones remain difficult to treat. These stones are difficult to fragment by ESWL, but can be dissolved using a variety of chemical methods. We have evaluated various techniques of chemical dissolution of cysteine using nephelometry, a simple but reliable technique that measures the intensity of monochromatic I ight scattered by a suspension. Our initial testing of this method showed a 1 inear relationship between cysteine concentration and light transmittance in the range of 2-6 mg/ml. The effect of pH on cysteine dissolution was also evaluated. The following solutions were tested: 8.4% bicarbonate (pH 10,7), 5% alpha-mercaptopropionylglycine in carbonate solution (pH 8.0), ),5% d-penicillamine in carbonate solution (pH 8, 10, and 11), 2% acetylcysteine in carbonate solution solution (pH 8, 10, and 11), and 2% acetylcysteine in 8.4% bicarbonate (pH 8). At pH 8.0, acetylcysteine was the most effective agent in
746
747
THR ROLP OP CHEMOLYSIS IN STONE MANAGEMENT. Stephen r. Dretl,:, Boston, MA (Presentation to be made by Dr. Dretler) with the emergence of ESWL and percutaneous ultrasonic lithotripsy (PUL), little attention has been paid to the usefulness of chemolysis. There are many clinical circumstances when cl,emolysis is invaluable for completing stone
RED CELL OXALATE FLUX IN PATIENTS UNDERGOING ESWL. Mani Menon, Worcester, Ma., *Robert A. Roth, Burlington, Ma., *Paul ~ Lee and*Tadeusz Strzelecki, Worcester, Ma. (Presented by Dr. Menon) We have shown that renal cortical mitochondria have a carrier system for the transport of oxalate (J.Biol .Chem. In Press) and that a decrease in transmembrane oxalate transport is the primary biochemical abnormality seen in one experimental mod~] of nephrolithiasis (J.Urol. 135:234A, 1986). Baggio et al have recently demonstrated that an alteration in red cell oxalate flux is present in a substantial proportion of patients with nephrolithiasis (N. Engl .J.Med. 314:599, 1986) and have hypothesized that this abnormality is an indicator of alterations in the transport of oxalate by renal cellular membranes. In order to characterize the changes in red cell oxalate flux that occur in nephrolithiasis, we have begun an evaluation of oxalate transport in patients undergoing ESWL. Oxalate fluxes were measured as previously described by Baggio and collegue1. Thirty subjects with no family or personal hi~tory of nephrolithiasis and 200 patients with renal stones form the study population. The measurement bf oxa 1ate trans port is performed by an investigator unaware of the clinical history and the code will be broken upon accrual of the designated number of study patients. The rate of oxalate transport will be correlated with the chemical composition of the renal stone, the volume of the stone burden, the metabolic activity of stone formation and, where possible, urinary and serum parameters conventionally measured in urolithiasis.
treatment:
for
large struvite calculi,infusion
of Renacidin after ESWL or PUL will both complGte stone therapy and decrease recurrence rates; dissolution of struvite fragments caught distal to a narrow but not totally obstructing infunclibulum; as a nonoperative method for successful manarJement of struvite "steinstrasse"
in patients with ileal and non-refluxing colon conduits; and for dissolvin9 struvite calculi transplanted kidneys. Uric acid calculi may be difficult to visualize during FSW~, even
with contrast.
in
If post ESWL ultrasound does not
demonstrate all uric acid fragments are small
enouyh to pass, Tromethamine-E (THA~-R) or NAf!C03 irrigation is used percutaneously or via ureteral catheter.
Uric acid ''Steinstrasse''
may be treated by PCN and THAM-E or NAHC03 irrigation. Cystine fragments left after PUL or ES\.'VL may be treated by TIIAM-E or Acetylcyst.ine chemolysis. DRG's for stone disease should not he so etched in stone as to financially prohibit the application of chemolysis for appropriate circumstances.
dissolving reagent grade cysteine.
However, in the more
alkaline range all the solutions had a similar effect which was superior to that seen at lower pH. The nephelometry data using reagent grade cysteine was compared to direct irrigation of cystine calculi removed from a patient via percutaneous extraction.
The rates of dissolution for
the various solutions were quite comparable to that seen with nephelometry suggesting that reagent grade cystine, which is readily avaj lab le and inexpensive, may be a useful model for further stuides to evaluate other methods to enhance the rate of the chemical dissolution of cystine stones. The carbonate solution that we developed appears to be an inexpensive, new solvent that is superior to currently recommended methods.
290A