Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model.

STUDY OBJECTIVE: The foraging of wild mushrooms can be complicated by toxicity from several mushroom types. Amatoxin, a peptide contained in several mushroom species, accounts for the majority of severe mushroom poisonings by binding to RNA polymerase II irreversibly, leading to severe hepatonecrosis. There is no effective antidote for severe amatoxin poisoning. We compare the effectiveness of 5 potential antidotal therapies in limiting the degree of hepatonecrosis in a randomized, controlled, murine model of amatoxin-induced hepatotoxicity. METHODS: One hundred eighty male Institute of Cancer Research mice were randomized into 6 equal groups. Within each group, 21 mice were intraperitoneally injected with 0.6 mg/kg of alpha-amanitin (amatoxin); the remaining 9 were injected with 0.9% normal saline solution. Four hours postinjection, each group of 30 mice was randomized to 1 of 5 intraperitoneal treatments (N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, or silybin) or normal saline solution. Repeated dosing was administered intraperitoneally every 4 to 6 hours for 48 hours. After 48 hours of treatment, each subject was killed, cardiac blood was aspirated for hepatic aminotransferase measurements (alanine transaminase and aspartate transaminase), and liver specimens were harvested to evaluate the extent of hepatonecrosis. The degree of hepatonecrosis was determined by a pathologist blinded to the treatment group and divided into 5 categories according to percentage of hepatonecrosis. RESULTS: Amanitin significantly increased aspartate transaminase in treated mice compared with normal saline solution-treated controls (mean [SD] 2,441 [2,818] IU/L versus 310 [252]; P=.03). None of the antidotal therapies were found to significantly decrease the increase in aminotransferases compared with controls. Further, none of the antidotal therapies demonstrated an important decrease in hepatonecrosis compared with controls when a histologic grading scale was used. CONCLUSION: In this murine model, N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin were not effective in limiting hepatic injury after alpha-amanitin poisoning. Increases of aminotransferases and degrees of histologic hepatonecrosis were not attenuated by these antidotal therapies.

Transureteral saline perfusion to obtain renal hypothermia: potential application in laparoscopic partial nephrectomy.

BACKGROUND: Partial nephrectomy for resection of renal tumors often requires renal artery clamping and external renal cooling using ice-slush. Laparoscopic surgery precludes traditional ice-slush cooling. To facilitate renal cooling during laparoscopic partial nephrectomy, we investigated a method of intrarenal cooling by retrograde transureteral iced saline perfusion. METHODS: Open laparotomy was performed in 6 pigs. After atraumatic renal artery clamping, one kidney was cooled externally by using standard ice-slush; the other was cooled transureterally. For transureteral cooling, the ureter was cannulated with a double lumen 12 Fr catheter. Chilled saline (4 degrees C) irrigation was flushed through the catheter into the renal pelvis (16.7 mL/min) and allowed to drain via the second lumen of the catheter. Using a 30-gauge hypodermic thermometer, kidney temperatures were measured at 5-minute intervals for 30 minutes at 3 locations and 2 depths (0.5 cm and 1.5 cm). The animals were euthanized, and the kidneys were harvested for histologic examination. RESULTS: Renal cooling was achieved with both external and transureteral cooling. However, lower (5.0 versus 26.1 degrees C, P<0.001) parenchymal temperatures were achieved more rapidly with external renal cooling. During transureteral cooling, medullary (1.5 cm) temperatures were lower than cortical (0.5 cm) temperatures were; this difference did not reach statistical significance. CONCLUSIONS: Although renal hypothermia can be achieved by transureteral iced saline infusion, external cooling by using ice-slush appears to be more efficient in the porcine model. With refinement of the technique, intrarenal cooling via a transureteral approach may allow more effective cooling of the renal medulla, and limit warm ischemia during laparoscopic partial nephrectomy.

Ancillary services in the health care industry: is Six Sigma reasonable?

Within the naval medical center construct, the disparate disciplines encompassed within ancillary services lend themselves to formal quality analysis and process improvement. This analysis uses the Six Sigma approach. Error rates were investigated and calculated for various processes within ancillary services at Naval Medical Center, San Diego. These were translated into the common metric of defects per million opportunities (DPMO). DPMO rates vary between 21.5 and 420,000. These correspond to Sigma values from 1.7 to approaching 6. Rates vary with biological complexity of the system and the degree of automation available. Some ancillary services translate well into a Six Sigma schema. Systems with high potential patient risk if performed poorly and those amenable to second checking and computer oversight may be candidates for such optimization. This should be undertaken in a local environment conducive to individual error reporting, and in a corporate environment with the will and funding to support the transition.