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Background: CroFab antivenin was recently FDA-approved. Methods: Prospectively collected data from 7 CroFab-treated rattlesnake bites seen in March/April 2001. Our treatment guideline, based on package insert, comprised attempts at initial control followed by 2 vials every 6 hrs x 3 doses with repeat outpatient labs 48-72 hrs later. Control was defined as a halt in proximal swelling and normal fibrinogen (fib), PT, and platelet count. Results: 7 pts received 1st doses of 6 or 8 vials in attempts to achieve control, but additional initial vials were given if control was not achieved. 2 pts with fib levels [is less than] 35 mg/dL remained hypofibrinogenemic despite 22 and 28 initial vials CroFab. Fib levels then became normal with scheduled dosing of 2 vials q 6 hrs, but both had recurrence of afibrinogenemia within 72 hrs. Both were readmitted and retreated, but neither achieved normal fib despite 12 and 19 additional vials of CroFab. 2 pts had thrombocytopenia which corrected with 6 vials without recurrence. 7 pts had swelling, and we achieved initial control of swelling in all pts with 6 to 16 vials. 2 pts then redeveloped progressive swelling during the next 24 hrs despite receiving 2 vials q 6 hrs. No immediate hypersensitivity reactions or serum sickness has been seen to date. Antivenin expenses and length of hospitalization were much greater than those with past use of Wyeth Antivenin. Conclusion: Initial 'control' of coagulopathy is frequently difficult to achieve with CroFab, and recurrence of severe coagulopathy developed within a few days of discontinuing CroFab. Swelling can progress after what appears to be initial control, despite regular dosing of antivenin., Ruha AM, Beuhler M, Brooks D, Wallace K, Graeme KA, Curry SC, Gerkin R, Lovecchio F. Good Samaritan Regional Medical Center, Phoenix [...]

Objective: To determine if intravenous (IV) hypertonic sodium bicarbonate is effective in the reversal of QRS widening associated with severe Taxus intoxication. Methods: 17 anesthetized swine were poisoned with an IV extract of Taxus media until doubling of the QRS interval on EKG was achieved. After poisoning (time 0), animals received either 4 mL/kg IV 8.4% Na[HCO.sub.3] (Experimental Group; 6 animals), a similar volume of 0.7% NaCl in 10% mannitol (Mannitol Group; 6 animals), or nothing (Control Group; 5 animals). Main outcome parameter was QRS duration. Secondary outcome parameters were mean arterial pressure (MAP), heart rate (HR), and cardiac index (CI = cardiac output/kg). Additionally, arterial pH, [PCO.sub.2], and plasma ionized calcium, sodium and potassium were monitored. Results: Taxus toxicity, defined as a 100% increase in QRS duration, was produced in all animals. Animals were similar in regard to baseline and time 0 physiologic parameters as well as amount of Taxus extract administered. Swine treated with Na[HCO.sub.3] had a statistically significant increase in pH and base excess compared with other groups. From time 5 through 30 minutes, following assigned treatment, no significant difference was detected between groups in QRS duration, MAP, HR, or CI. With a 2-tailed a of .05, we had 98% power to detect a 50% narrowing in QRS duration between groups if it would have occurred, but were unable to do so. Conclusion: Hypertonic sodium bicarbonate was ineffective in reversing the widening of QRS interval associated with Taxus poisoning in this swine model., Ruha AM, Tanen DA, Graeme KA, Curry SC, Miller MB, Gerkin R, Reagan CG, Brandon T. Good Samaritan Regional Medical Center, Phoenix, [...]

Background: Exposure to prescription diet drugs other than amphetamine and methamphetamine may cause GC/MS-confirmed, and therefore chemically specific, positive urine drug tests for amphetamine. This is explained by the metabolism of these drugs, e.g., clobenzorex, to amphetamine, which is then excreted in amounts that exceed federal drug test cut-off levels. Drug reference information and laboratory standards needed to verify exposure to such drugs are largely unavailable. A case is presented that demonstrates the value of analytical laboratory investigation beyond the initial GC/MS confirmation of the urinary presence of amphetamine. Case Report: Investigation of a GC/MS-confirmed laboratory positive workplace urine test for amphetamine suggested use of an unidentified Mexican diet drug by the specimen donor. Pharmaceutical reference source consultation tailed to reveal the identity of donor-provided drug samples. Discussion with a US representative of the suspected pharmaceutical manufacturer and GC/MS analysis of the drug samples strongly suggested, but did not confirm, that the samples contained clobenzorex. Self-administration of drug sample by one of the authors, followed by chemical derivatization, solid phase extraction, and GC/MS analysis of urine collected at 4 hours postexposure revealed acetylated derivatives of clobenzorex (S-(+)-N-(2-chlorobenzyl)-amphetamine) and associated metabolites, including amphetamine, 4-OH-amphetamine, and norephedrine. Conclusion: Demonstration of the urinary presence of clobenzorex metabolites other than amphetamine by GC/MS analysis corroborates exposure to clobenzorex as an explanation for a GC/MS-confirmed positive urine drug test for amphetamine., Wallace KL, Gerkin R, Gatewood P. Good Samaritan Regional Medical Center, Phoenix, [...]

Objective: To evaluate the respiratory toxicity associated with exposure to low concentrations of products of combustion during firefighter overhaul, which involves searching for and extinguishing possible sources of reignition. Methods: Firefighters were monitored at baseline and again after completing overhaul. Testing included spirometry and serum pneumoprotein [Clara cell protein (CC16) and surfactant-associated protein A (SP-A)] assessments. One group of firefighters wore no respiratory protection (NRP) while the other group wore air-purifying respirators (APR). Results: The results are summarized in the following table. Group n CC16 ([micro]g/L) SP-A ([micro]g/L) NRP-baseline 25 8.92 [+ or -] 3.52 287.0 [+ or -] 144.3 NRP-overhaul 25 12.34 [+ or -] 3.61 305.7 [+ or -] 156.7 p = 0.003 p = 0.539 APR-baseline 26 9.55 [+ or -] 3.50 250.3 [+ or -] 117.4 APR-overhaul 26 14.57 [+ or -] 5.22 333.7 [+ or -] 140.7 p < 0.001 p = 0.001 Group n FVC (L) [FEV.sub.1] (L) NRP-baseline 19 5.43 [+ or -] 0.70 4.06 [+ or -] 0.64 NRP-overhaul 19 5.36 [+ or -] 0.73 3.94 [+ or -] 0.65 p = 0.228 p = 0.097 APR-baseline 24 5.38 [+ or -] 0.66 4.16 [+ or -] 0.48 APR-overhaul 24 5.23 [+ or -] 0.72 4.05 [+ or -] 0.64 p = 0.001 p = 0.005 Conclusions: Overhaul increased CC16 in both groups. CC16 has been shown to increase with altered alveolar-capillary permeability, but the clinical significance of this change has not yet been determined. Contrary to expectations, SP-A increased and FVC and [FEV.sub.1] decreased in the firefighters wearing APR. Continuing analysis will focus on differences in levels of chemical exposure between the two groups. Firefighter respiratory exposures during overhaul have the potential to cause changes in spirometry and lung permeability. Burgess JL, Nanson CJ, Bolstad-Johnson DM, Gerkin R, Hysong T, Lantz RC, Sherrill DL, Quan SF, Witten ML. University of Arizona, Tucson, AZ; City of Phoenix Fire Department, Phoenix, AZ, Burgess JL, Nanson CJ, Bolstad-Johnson DM, Gerkin R, Hysong T, Lantz RC, Sherrill DL, Quan SF, Witten ML. University of Arizona, Tucson, AZ; City of Phoenix Fire Department, Phoenix, [...]

Background: Salicylate (SAL) toxicity, in vitro, produces mitochondrial membrane permeability transition (MPT), an inner membrane pore formed, at least in part, from the adenine nucleotide transporter (ANT) and cyclophilin-D (CyP-D). MPT increases permeability of the inner membrane to molecules < 1500 Da, including [H.sup.+], thereby uncoupling oxidative phosphorylation. Cyclosporine A (CSA) inhibits SAL-induced MPT formation in vitro by binding to CyP-D. This study's purpose was to determine if pretreatment with CSA prolongs survival time in rats poisoned with SAL. Methods: 29 rats were randomized to receive pretreatment with either 30 mg/kg CSA or an equal volume of control diluent IP. 4 h later, when circulating [CSA] exceeded concentrations that had been shown to prevent MPT in vitro, all rats received 1700 mg/kg sodium SAL IP. Time until death was recorded. Heart blood for measurement of serum [CSA] and [SAL] were obtained immediately after death. With 11 animals in each group, we calculated a power of > 0.95 to detect a doubling of survival time. Results: Median survival time in controls was 18 minutes (95% C. I. of 14-22 minutes) and for CSA animals was 14 minutes (95% C.I. of 13-15 minutes). The log rank test for the survival distributions between the 2 groups was significant, indicating shortened survival time for the CSA group (p < 0.001). Using Cox proportional hazards, salicylate level did not significantly influence survival time (p = 0.60). Conclusion: Pre-treatment with CSA shortened survival time in rats with SAL toxicity., Katz K, Curry S, Brooks D, Gerkin R, Ruha AM, Beuhler M, Watts D. Good Samaritan Regional Medical Center, Phoenix, Arizona, [...]

Objective: Lung inflammation may lead to accelerated rate of decline in lung function. Interleukin-10 (IL-10) suppresses inflammation through modulation of inflammatory mediators. The IL-10 single nucleotide polymorphism (SNP) at -1082 is associated with differential expression of IL-10, and the effects of other IL-10 SNPs have not been as well characterized. To purpose of the study was to evaluate the role of IL-10 SNPs in susceptibility to accelerated loss of lung function. Methods: Blood or mouthwash samples were collected from City of Phoenix Fire Department firefighters after obtaining informed consent. Information on age, present smoking, and annual forced expiratory volume in one second (FE[V.sub.1]) were collected from medical surveillance records. DNA was extracted from blood using alcohol precipitation and from buccal cells using Qiagen QiaAmp DNA mini Kit. IL-10 SNPs at -1082 and -819 were screened using the TaqMan[R] assay. Results: 314 subjects with at least three annual FE[V.sub.1] tests were included in the study. Average age was 41.6 [+ or -] 7 years, 18% were ever smokers, and annual mean decline in FE[V.sub.1] was -40 [+ or -] 40 ml. Genotype frequencies at -1082 were AA 31%, AG 50% and GG 17%, and at -952 were CC 55%, CT 37% and TT 8%. After adjusting for baseline FE[V.sub.1], age, and smoking using linear regression analysis, there were no significant differences in annual decline for SNPs at -1082 (p = 0.974) and -819 (p = 0.126). Conclusion: There were no associations between IL-10 SNPs at -1082 and -819 and longitudinal decline in lung function in our study population. Inclusion of environmental and occupational exposure data and analysis of additional cytokine polymorphisms may help to better define the genetic basis of variation in decline in lung function., Fierro MA, Burgess JL, Hysong TA, Fleming JE, Conley SM, Gerkin R, Klimecki W. University of Arizona, Tucson, AZ; Good Samaritan Medical Center, Phoenix, [...]