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5. Royal academy of medicine in Ireland international conference on homocysteine metabolism from basic science to clinical medicine: Proceedings of meeting held at Dromoland Castle, Co. Clare on July 2nd–6th, 1995

Author

Björkegren, K., Bergmark, C., de Faire, U., Mansoor, M. Azam, Svardal, A., Bostom, A. G., Roubenoff, R., Dellaripa, P., Nadeau, M. R., Sutherland, P., Wilson, P. W. F., Jacques, P. F., Selhub, J., Rosenberg, I. H., Bostom, A. G., Brosnan, J. T., Hall, B., Nadeau, M. R., Selhub, J., Bostom, A. G., Shemin, D., Lapane, K. L., Sutherland, P., Nadeau, M. R., Wilson, P. W. F., Selhub, J., Bostom, A. G., Shemin, D., Nadeau, M. R., Selhub, J., Bostom, A. G., Selhub, J., Jacques, P. F., Nadeau, M. R., Williams, R. R., Ellison, R. C., Cuskelly, G. J., McNulty, H., Strain, J. J., McPartlin, J. M., Scott, J. M., Chadefaux-Vekemans, B., Coudé, M., Aupetit, J., Kamoun, P., Coudé, M., Aral, B., Zabot, M. T., Aupetit, J., Kamoun, P., Chadefaux-Vekemans, B., Calaf, R., Ghiringelli, O., Barlatier, A., Charpiot, P., Rolland, P. H., Garçon, D., Charpiot, P., Augier, T., Chareyre, C., Rolland, P. H., Garçon, D., Chango, A., Hodez, F., Tronel, H., Nuel, G., Michel, F., Frémont, S., Méjean, L., Nicolas, J. P., Candito, M., Chambon, P., Gibelin, P., Amsellem, J., Baudouy, M., Morand, P., Candito, M., Chambon, P., Pringuey, D., Aubin-Brunet, V., Beaulieu, F., Darcourt, G., Bedoucha, P., Alchaar, H., Chatel, M., Candito, M., de Valk, H. W., van der Griend, R., Eeden, M. K. G. van, de Groot, E., Duran, M., Smeitink, J. A. M., de Klerk, J. B. C., Wittebol-Post, D., Rolland, M. -O., Haas, F. J. L. M., Meuwissen, O. J. A. Th., Banga, J. D., Poll-The, B. T., de Vries, J. I. P., Dekker, G. A., van Geijn, H. P., Huigens, P. C., Jakobs, C., von Blomberg, B. M. E., Deulofeu, R., Giralt, M., Aibar, C., Bauchet, C., Ballesta, A. M., Varela, G., Vila, N., Chamorro, A., Casals, F. J., Cremades, J. Diaz, Daly, L., Meleady, R., Graham, I., den Heijer, M., Brouwer, I. A., Gerrits, W. B. J., Bos, G. M. J., Blom, H. J., den Heijer, M., Bos, G. M. J., Koster, T., Vandenbroucke, J. P., Blom, H. J., Briët, E., Rosendaal, F. R., Fischer, G., Behrend, C., Bartholmes, P., Fermo, I., Paroni, R., Vigano, S., D’Angelo, A., Fermo, I., Paroni, R., Vigano, S., D’Angelo, A., Franken, D. G., Boers, G. H. J., Blom, H. J., Hamel, B. C. J., Franken, D. G., Boers, G. H. J., Blom, H. J., Ruijs, J. H. J., Franken, D. G., Blom, H. J., Boers, G. H. J., Tangerman, A., Guttormsen, A. B., Ueland, P. M., Refsum, H., Svarstad, E., Gao, W., Goldman, E., Jakubowski, H., Sebastio, G., Sperandeo, M. P., de Franchis, R., Andria, G., Garrow, T. A., Hladovec, J., Sommerova, Z., Písariková, A., Halsted, C. H., Villanueva, J., Chandler, C. J., Stabler, S. P., Allen, R. H., Muskhelishvili, L., James, S. J., Poirer, L., Jacobsen, D. W., Savon, S. R., DiCorleto, P. E., Jourdheuil-Rahmani, D., Rolland, P. H., Garçon, D., Joosten, E., Riezler, R., Allen, R., Joosten, E., Riezler, R., Allen, R., Marquardt, T., Ullrich, K., Harms, E., Koch, H. G., Koch, H. G., Evers, S., Grotemeyer, K. H., Vogelpohl, L., von Eckardstein, A., Ullrich, K., Deufel, T., Kraus, J., Harms, E., Kozich, V., Janosik, M., Sokolová, J., Bukovská, G., Kraus, J. P., Kluitmans, L. A. J., van den Heuvel, L. P., Stevens, E., Trubels, J. M. F., Blom, H. J., Boers, G. H. J., van Oost, B. A., Kraus, J. P., Kittner, S., Macko, R., Hebel, J. R., Rohr, J., Malinow, M. R., Upson, B., Buchholz, D., Earley, C., Johnson, C., Price, T. R., Rosario, J., Sloan, M., Stern, B., Wityk, R., Wozniak, M., Sherwin, R., Stolley, P., Kluijtmans, L., Heuvel, L. van den, Stevens, E., Trijbels, F., Blom, H., Boers, G., van Oost, B., den Heijer, M., Rozen, R., Löhrer, F., Angst, C., Fowler, B., Zaugg, M., Brunner, F., Haefeli, W. E., Nedrebø, B., Ericsson, U. -B., Ueland, P. M., Refsum, H., Lien, E. A., London, J., Paly, E., Paul, V., Paris, D., Kamoun, P., Chassé, J. F., Møller, J., Rasmussen, K., Meleady, R., Graham, I., Daly, L., Verhoef, P., Meleady, R., Graham, I., Daly, L., McMartin, K. E., Phifer, T. J., Alexander, J. S., Middlebrooks, M., Childress, L. E., Nicolas, J. P., Tronel, H., Chango, A., Fremont, S., Felden, F., Guerci, B., Creton, C., Drouin, P., Oakley, G. P., Elias, P. R. P., Hann, A. C., Curtis, C. G., Rose, F. A., Tudball, N., Parrot-Roulaud, F., Cochet, C., Catargi, B., Leprat, F., Latapie, J. -L., Perna, A. F., De Santo, N. G., Ingrosso, D., Galletti, P., Zappia, V., Parrot-Roulaud, F., Sassoust, G., Boissieras, P., Blom, H. J., Majors, A. K., Ehrhart, L. A., Pezacka, E. H., Perry, I. J., Morris, R. W., Ebrahim, S. B., Shaper, A. G., Refsum, H., Ueland, P. M., Pietrzik, K., Dierkes, J., Kroesen, M., Bung, P., Rasmussen, K., Moller, J., Rasmussen, K., Remacha, A., Garcia-Die, F., Cadafalch, J., Barceló, H. J., Parellada, H., Regland, B., Gottfries, C. -G., Andersson, M., Bagby, J., Dyrehag, L. -E., Abrahamsson, L., Ronge, E., Kjellman, B., Frosst, P., Christensen, B., Goyette, P., Rosenblatt, D. S., Genest, J., Rozen, R., Riedel, B., Ueland, P. M., Svardal, A. M., Silberberg, J., Crooks, R., Fryer, J., Ray, C., Guo, X. W., Xie, L., Dudman, N., Silberberg, J., Crooks, R., Fryer, J., Ray, C., Guo, X. W., Xie, L., Dudman, N., Silberberg, J., Crooks, R., Fryer, J., Ray, C., Guo, X., Xie, L., Dudman, N., Smith, B., Kohlman-Trigoboff, D., Simsir, S., Stabler, S. P., Allen, R. H., Strydom, A. J. C., Schlüssel, E., Preibisch, G., Elstner, E. F. E., Pütter, S., Spuijbroek, M. D. E. H., Goddijn-Wessel, T. A. W., Wouters, M. G. A. J., Molen, E. F. v. d., Blom, H. J., Boers, G. H. J., Steegers-Theunissen, R. P. M., Trijbels, J. M. F., Thomas, C. M. G., Eskes, T. K. A. B., Tsai, M. Y., Hanson, N., Key, N., Schwichtenberg, K., Garg, U., Todesco, L., Fowler, B., Pollaert, N., Haefeli, W. E., Thorand, B., Hages, M., Pietrzik, K., Bung, P., Holzgreve, W., Vila, N., Chamorro, A., Deulofeu, R., Aibar, C., Giralt, M., Ballesta, A. M., van der Mooren, M. J., Wouters, M. G. A. J., Schellekens, L. A., Eskes, T. K. A. B., Rolland, R., Blom, H. J., Put, N. v. d., Trijbels, F., Heuvel, L. v. d., Blom, H., Eskes, T., Steegers-Theunissen, R., Mariman, E., Heyer, M. d., Rozen, R., Daher, R., Van Lente, F., Vilkovsky, A. B., Maev, I. V., Richter, E. L., Kirnus, M. D., Varela-Moreiras, G., Alonso-Aperte, E., Rubio, M., Gassó, M., Deulofeu, R., Alvarez, L., Caballeria, J., Rodés, J., Mato, J. M., van Aerts, L. A. G. J. M., Peereboom-Stegeman, J. H. J. Copius, Noordhoek, J., Eskes, T. K. A. B., Molen, E. F. v. d., Spuijbroek, M. D. E. H., Eskes, T. K. A. B., Heuvel, L. P. v. d., Monnens, L. A. H., Blom, H. J., van Guidener, C., Janssen, M. J. F. M., Surachno, J., Stehouwer, C. D. A., van den Berg, M., Bierdrager, E., Rauwerda, J. A., Wilcken, B., Hammond, J., Wouters, M. G. A. J., Hamilton, C. J. C. M., Blom, H. J., Boers, G. H. J., Thomas, C. M. G., Borm, G. F., Eskes, T. K. A. B., Wang, H., Tsai, J. -C., Perrella, M. A., Yoshizumi, M., Sibinga, N. E. S., Haber, E., Chang, T. H. -T., Schlegel, R., Lee, M. -E., Woodside, J., McMaster, D., Yarnell, J., Young, I., Mercer, C., Byrne, K., Evans, A., Gey, F., Gao, X. M., Dougan, G., Wordsworth, P., McMichael, A., Young, P. B., Kennedy, D. G., Molloy, A. M., Scott, J. M., Ward, P., Naughten, E., Cahalane, S., Murphy, D., Mayne, P., Chauveau, P., Chadefaux-Vekemans, B., Coudé, M., Aupetit, J., Kamoun, P., Jungers, P., van Asselt, D. Z. B., Blom, H. J., de Wild, G. M., van Staveren, W. A., Hoefnagels, W. H. L., Naruszewicz, M., Staniewicz, A., Dziewanowski, K., Evrovski, J., Cole, D. E. C., Callaghan, Michael, Lindgren, A., Brattström, L., Hultberg, B., Verhoef, P., Hennekens, C. H., Allen, R. H., Stabler, S. P., Willett, W. C., Stampfer, M. J., Frantzen, F., Sundrehagen, E., Verhoef, P., Kok, F. J., Stampfer, M. J., Willett, W. C., Gaziano, J. M., Hennekens, C. H., Allen, R. H., Stabler, S. P., Reynolds, R. D., Hsu, R. -J., Shane, B., Robinson, K., Kottke-Marchant, K., Green, R., Gupta, A., Jacobsen, D., Robinson, K., Mayer, E., Gupta, A., Miller, D., Marchant, K., Green, R., Jacobsen, D., Greene, R., Chong, Y. -Y., Jacobsen, D., Robinson, K., Gupta, M., Sheppard, C. A., Matthews, R. G., Goyette, P., Frosst, P., Rozen, R., Verhoef, P., Kok, F. J., Kruyssen, H. A. C. M., Witteman, J. C. M., Ueland, P. M., Boushey, C., Beresford, S., Omenn, G., Motulsky, A. G., Nygard, O., Vollset, S. E., Kvale, G., Stensvold, I., Ueland, P. M., Refsum, H., Fiskerstrand, T., Ueland, P. M., Refsum, H., Bugge, K. H., Oshaug, A., Bjønnes, C. H., Refsum, H., Wu, J. T., Wu, L. L., and Wilson, L. W.

Published
1995
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9. Hysteroscopic Tubal Sterilization: An Evidence-Based Analysis

Author

McMartin, K

Subjects
Adult, Ontario, Pain, Postoperative, Time Factors, Sterilization, Tubal, Humans, Minimally Invasive Surgical Procedures, Female, Hysteroscopy, Fallopian Tubes, United States, Research Article
Abstract

Hysteroscopic tubal sterilization is a minimally invasive alternative to laparoscopic tubal ligation for women who want permanent contraception. The procedures involves non-surgical placement of permanent microinserts into both fallopian tubes. Patients must use alternative contraception for at least 3 months postprocedure until tubal occlusion is confirmed. Compared to tubal ligation, potential advantages of the hysteroscopic procedure are that it can be performed in 10 minutes in an office setting without the use of general or even local anesthesia.The objective of this analysis was to determine the effectiveness and safety of hysteroscopic tubal sterilization compared with tubal ligation for permanent female sterilization.A standard systematic literature search was conducted for studies published from January 1, 2008, until December 11, 2012.Observational studies, randomized controlled trials (RCTs), systematic reviews and meta-analyses with 1 month or more of follow-up were examined. Outcomes included failure/pregnancy rates, adverse events, and patient satisfaction.No RCTs were identified. Two systematic reviews covered 22 observational studies of hysteroscopic sterilization. Only 1 (N = 93) of these 22 studies compared hysteroscopic sterilization to laparoscopic tubal ligation. Two other noncomparative case series not included in the systematic reviews were also identified. In the absence of comparative studies, data on tubal ligation were derived for this analysis from the CREST study, a large, multicentre, prospective, noncomparative observational study in the United States (GRADE low). Overall, hysteroscopic sterilization is associated with lower pregnancy rates and lower complication rates compared to tubal ligation. No deaths have been reported for hysteroscopic sterilization.A lack of long-term follow-up for hysteroscopic sterilization and a paucity of studies that directly compare the two procedures limit this assessment. In addition, optimal placement of the microinsert at the time of hysteroscopy varied among studies.Hysteroscopic sterilization is associated with: lower pregnancy rates compared to tubal ligation (GRADE very low); lower complication rates compared to tubal ligation (GRADE very low); no significant improvement in patient satisfaction compared to tubal ligation (GRADE very low).Hysteroscopic tubal sterilization is a minimally invasive alternative to conventional tubal ligation for women who want a permanent method of contraception. Both approaches involve closing off the fallopian tubes, preventing the egg from moving down the tube and the sperm from reaching the egg. Tubal ligation is a surgical procedure to tie or seal the fallopian tubes, and it usually requires general anesthesia. In contrast, hysteroscopic tubal sterilization can be performed in 10 minutes in an office setting without general or even local anesthesia. A tiny device called a microinsert is inserted into each fallopian tube through the vagina, cervix, and uterus without surgery. An instrument called a hysteroscope allows the doctor to see inside the body for the procedure. Once the microinserts are in place, scar tissue forms around them and blocks the fallopian tubes. Health Quality Ontario conducted a review of the effectiveness and safety of hysteroscopic tubal sterilization compared to tubal ligation. This review indicates that hysteroscopic tubal sterilization is associated with: lower pregnancy rates compared to tubal ligation; lower complication rates compared to tubal ligation; no significant improvement in patient satisfaction compared to tubal ligation. However, we found a number of limitations to the studies available on hysteroscopic tubal sterilization. Among other concerns, most studies did not include long-term follow-up and only 1 study directly compared hysteroscopic tubal sterilization to tubal ligation.

Published
2013

11. FORMATE KINETICS IN METHANOL POISONING

Author

Kerns, W, Tomaszewski, C, McMartin, K, Ford, M, and Brent, J

Subjects
Methanol -- Health aspects, Poisoning -- Physiological aspects, Environmental issues, Health, Pharmaceuticals and cosmetics industries
Abstract

Objective: We sought to describe the kinetics, dialysis clearance, & clinical markers of formate (FA), the toxic metabolite of methanol (MeOH). Methods: Data were obtained from a prospective, multicenter treatment protocol using fomepizole [+ or -] hemodialysis (HD) for MeOH poisoning. HD indications included: MeOH [is greater than] 50 mg/dl, pH [is less than] 7.1, refractory acidosis, or altered visual acuity. Blood samples were drawn for serial FA, MeOH, pH, & bicarbonate measurements. Plasma MeOH & FA were determined by gas chromatography. Elimination half-life ([t.sub.1/2]) was calculated as [t.sub.1/2] = 0.693/Kd, where Kd, the elimination rate constant, was determined from the slope of ln[FA] vs time. HD clearance was calculated using the relationship HD flow x [(inlet FA - outlet FA)/inlet FA]. Pearson correlation coefficients were determined for initial FA vs initial pH, serum bicarbonate, & anion gap (AG). Data were analyzed using SAS statistical software (p [is less than] 0.05 significant). Results: 11 patients (10 males) with mean age 39.9 years (range 19-61) were included. 7 patients underwent HD. The mean initial MeOH was 196.3 mg/dL (range 28-768) & FA, 11.0 mmol/L (range 0-34.8). Non-HD [t.sub.1/2] was 205 min [+ or -] 25 sd and HD [t.sub.1/2], 185 min [+ or -] 62.7 sd (NS by Student's t-test). Overall HD FA clearance was 223 mL/min [+ or -] 24.5 sd. Correlation coefficients were: pH vs FA [r.sup.2] = 0.929 (p [is less than] 0.05); bicarbonate vs FA [r.sup.2] = 0.804 (p [is less than] 0.05); & AG vs FA [r.sup.2] = 0.760 (p [is less than] 0.05). Conclusions: Even though HD clears FA, HD does not decrease the FA elimination [t.sub.1/2]. Low pH, low bicarbonate, and elevated AG correlate with FA presence., Kerns W, Tomaszewski C, McMartin K, Ford M, Brent J, META Study Group. Carolinas Medical Center, Charlotte, NC; Louisiana State University, Shreveport, LA; and University of Colorado Health Sciences Center, [...]

Published
1999

12. FOMEPIZOLE ELIMINATION KINETICS IN FULMINANT HEPATIC FAILURE

Author

Wax, P and McMartin, K

Subjects
Liver failure -- Care and treatment, Acetaminophen -- Health aspects, Substance abuse -- Case studies, Environmental issues, Health, Pharmaceuticals and cosmetics industries
Abstract

Background: Fomepizole (4MP) is predominantly eliminated by hepatic metabolism. We present a patient in fulminant liver failure who had an ethylene glycol (EG) level of 50 mg/dL and was treated with a single dose of fomepizole. Serial serum fomepizole levels were obtained over the next 7 days to investigate the elimination of fomepizole in this virtually anhepatic patient. Case Report: A 38-year-old male presented to the ED with fulminant hepatic failure from chronic acetaminophen (APAP) and ethanol abuse. Upon presentation he was unresponsive and had a pH of 7.15, AST of 8580 IU/L, T Bili of 2.5 mg/dL, ammonia of 119 [micro]mol/L, INR of 6.1, creatinine of 1.8 mg/dL, APAP level of 31 mcg/mL, and ethylene glycol level of 50 mg/dL. The patient was treated with NAC and a single intravenous dose of fomepizole 15 mg/kg (total 1050 mg). Subsequently, the EG level was discovered to be a false positive and no further fomepizole was given. The initial fomepizole level 1 hour after administration was 204 [micro]mol/L. The rate of elimination was 2.9 [micro]mol/L/h. In the recent clinical trial on fomepizole in EG poisoning the rate of elimination was 16.5 [+ or -] 3.1 [micro]mol/L/h. Conclusion: Therapeutic doses of fomepizole (4MP) are eliminated normally by nonlinear or zero order kinetics. These doses produce blood levels in the range of 100-300 [micro]mol/L. Studies in healthy humans have shown that fomepizole is eliminated from the body primarily by hepatic metabolism. The nonlinear elimination probably results because of a saturation of this metabolic pathway. In this patient, the elimination of a single IV dose of 4MP was not saturated, but followed classic first order kinetics, with a half-life of 17.8 hours. In comparison, Phase 1 studies in healthy humans showed that the elimination of 4MP, after the initial saturation phase, was first order, with half-lives about 2 hours. These data suggest that in this patient the metabolism of fomepizole was completely blocked by the loss of liver function. Hence, the elimination occurred by excretory processes (most likely in the urine), which are first order processes., Wax P, McMartin K. University of Rochester, Rochester NY; Louisiana State University Medical Center, Shreveport, [...]

Published
1999

13. Methanol

Author

Tephly, T. R., primary, Makar, A. B., additional, McMartin, K. E., additional, Hayreh, S. S., additional, and Martin-Amat, G., additional

Published
1979
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14. Exposure to organic solvents. Does it adversely affect pregnancy?

Author

McMartin, K. I. and Koren, G.

Subjects
Adult, Pregnancy Complications, Pregnancy, Occupational Exposure, Solvents, Humans, Female, Organic Chemicals, Risk Assessment, Research Article, Congenital Abnormalities
Abstract

QUESTION: One of my patients is a laboratory technician who routinely handles organic solvents. She has just learned that she is pregnant, and she depends very much on this job because her husband is unemployed. What is the risk to her unborn baby? ANSWER: Available epidemiologic data indicate your patient's fetus might be at increased risk for malformations. We recommend that she minimize her occupational exposure to organic solvents by routinely using ventilation systems and protective equipment. This is most important during the first trimester of pregnancy.

Published
1999

16. Renal toxicity of ethylene glycol--is it oxalate or calcium oxalate?

Author

Guo, C and McMartin, K

Subjects
Ethylene glycol -- Health aspects, Acute renal failure -- Causes of, Oxalates -- Physiological aspects, Environmental issues, Health, Pharmaceuticals and cosmetics industries
Abstract

Background: Ethylene glycol (EG) poisoning results in an acute renal failure that is linked with proximal tubular cell necrosis and metabolism of EG to oxalate (OX). One mechanism for the renal failure is that OX crystallizes within the tubular lumen as calcium oxalate (COM), leading to luminal blockage and compression-induced loss of glomerular filtration. However, others have suggested that COM or OX induces cytotoxic damage, leading to tubular necrosis and renal failure. Our initial studies using normal human proximal tubule (HPT) cells in culture showed that OX, but not glycolate nor glyoxylate, produced' toxicity. In the present studies, we compared the toxicity of COM with that of NaOX on HPT cells in order to assess which may produce greater cytotoxic damage. Methods: Confluent cultures of HPT cells were exposed to buffers containing pre-formed COM crystals (0,1,3 & 5 mM), sodium oxalate (NaOX at 0,1,3 & 5 mM), or NaOX (0-5 mM) plus EDTA (4 mM) for 6 hours at 37[degrees]C. Cytotoxicity was assessed by measuring the release of lactate dehydrogenase (LDH) into the external buffer and the activity of [gamma]-glutamyl transpeptidase (GGT) in solubilized cells. Results: NaOX and COM produced similar dose-dependent increases in LDH release and decreases of GGT activity. The effects of NaOX on LDH were partially reduced by EDTA, while those on GGT were not reduced by EDTA. Conclusion: The results indicate that COM and OX, on an equimolar basis, induce toxicity in HPT cells in roughly the same proportion, although part of the effects of OX may be due to formation of COM in solution (since the effects of OX are partially reduced by EDTA)., Guo C, McMartin K. Department of Pharmacology, Louisiana State University Health Science Center, Shreveport, [...]

Published
2002

17. The authors' reply

Author

Manini, A. F., primary, Hoffman, R. S., additional, McMartin, K. E., additional, and Nelson, L. S., additional

Published
2009
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22. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group.

Author

Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M, Kulig K, Methylpyrazole for Toxic Alcohols Study Group, Brent, J, McMartin, K, Phillips, S, Burkhart, K K, Donovan, J W, Wells, M, and Kulig, K

Abstract

Background: Ethylene glycol poisoning causes metabolic acidosis and renal failure and may cause death. The standard treatment is inhibition of alcohol dehydrogenase with ethanol, given in intoxicating doses, and adjunctive hemodialysis. We studied the efficacy of fomepizole, a new inhibitor of alcohol dehydrogenase, in the treatment of ethylene glycol poisoning.Methods: We administered intravenous fomepizole to 19 patients with ethylene glycol poisoning (plasma ethylene glycol concentration, > or =20 mg per deciliter [3.2 mmol per liter]). Patients who met specific criteria also underwent hemodialysis. Treatment was continued until plasma ethylene glycol concentrations were less than 20 mg per deciliter. Acid-base status, renal function, the kinetics of fomepizole, and ethylene glycol metabolism were assessed at predetermined intervals.Results: Fifteen of the patients initially had acidosis (mean serum bicarbonate concentration, 12.9 mmol per liter). Acid-base status tended to normalize within hours after the initiation of treatment with fomepizole. One patient with extreme acidosis died. In nine patients, renal function decreased during therapy; at enrollment, all nine had high serum creatinine concentrations and markedly elevated plasma glycolate concentrations (> or =97.7 mg per deciliter [12.9 mmol per liter]). None of the 10 patients with normal serum creatinine concentrations at enrollment had renal injury during treatment; all 10 had plasma glycolate concentrations at or below 76.8 mg per deciliter (10.1 mmol per liter). Renal injury was independent of the initial plasma ethylene glycol concentration. The plasma concentration of glycolate and the urinary excretion of oxalate, the major metabolites of ethylene glycol, uniformly fell after the initiation of fomepizole therapy. Few adverse effects were attributable to fomepizole.Conclusions: In patients with ethylene glycol poisoning, fomepizole administered early in the course of intoxication prevents renal injury by inhibiting the formation of toxic metabolites. [ABSTRACT FROM AUTHOR]

Published
1999

23. Pregnancy outcome following gestational exposure to organic solvents: a prospective controlled study.

Author

Khattak S, K-Moghtader G, McMartin K, Barrera M, Kennedy D, Koren G, Khattak, S, K-Moghtader, G, McMartin, K, Barrera, M, Kennedy, D, and Koren, G

Abstract

Context: Numerous women of childbearing age are exposed occupationally to organic solvents. Previous retrospective studies have reported conflicting results regarding teratogenic risk.Objective: To evaluate pregnancy and fetal outcome following maternal occupational exposure to organic solvents.Design: A prospective, observational, controlled study.Setting: An antenatal counseling service in Toronto, Ontario.Patients: One hundred twenty-five pregnant-women who were exposed occupationally to organic solvents and seen during the first trimester between 1987 and 1996. Each pregnant woman who was exposed to organic solvents was matched to a pregnant woman who was exposed to a nonteratogenic agent on age (+/-4 years), gravidity (+/-1), and smoking and drinking status.Main Outcome Measure: Occurrence of major congenital malformations.Results: Significantly more major malformations occurred among fetuses of women exposed to organic solvents than controls (13 vs 1; relative risk, 13.0; 95% confidence interval, 1.8-99.5). Twelve malformations occurred among the 75 women who had symptoms temporally associated with their exposure, while none occurred among 43 asymptomatic exposed women (P<.001). (One malformation occurred in a woman for whom such information was missing.) More of these exposed women had previous miscarriage while working with organic solvents than controls (54/117 [46.2%] vs 24/125 [19.2%]; P<.001). However, exposed women who had a previous miscarriage had rates of major malformation that were similar to exposed women who had no previous miscarriage.Conclusions: Occupational exposure to organic solvents during pregnancy is associated with an increased risk of major fetal malformations. This risk appears to be increased among women who report symptoms associated with organic solvent exposure. Women's exposure to organic solvents should be minimized during pregnancy. Symptomatic exposure appears to predict higher fetal risk for malformations. [ABSTRACT FROM AUTHOR]

Published
1999
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25. List of Contributors

Author

Abdolahi, A., Abdolghaffari, A.H., Abdollahi, M., Achanzar, W.E., Acquisto, N.M., Adatsi, F.K., Adekola, F.A., Agarwal, D., Aizawa, H., Akbar Malekirad, A., Allen, J.A., Allison, B., Alonso Blazquez, N., Altkorn, R., Amanlou, M., Amini, M., Anand, S.S., Andres, S.A., Angelini, D.J., Angelo, G., Api, A.M., Apte, U., Armendáriz, C.R., Asha, S., Atlason, P., Attene-Ramos, M.S., Austin, C.P., Babich, M.A., Badanthadka, M., Baeeri, M., Baer, K.N., Baghaei, A., Bahadar, H., Balali-Mood, B., Balali-Mood, M., Bale, A.S., Ballantyne, B., Banasik, M., Banks, C.N., Banton, M., Baran, K.P., Barata, C., Barefoot, A.C., Barlow, S.M., Barr, D.B., Barrueto, F., Barton, C., Barton, N., Battalora, M., Bayrami, Z., Bazl, R., Beckett, R.D., Bečková, V., Beedanagari, S., Behboudi, A.F., Beilke, L.D., Beltrán, E.M., Benson, A., Bergamo, L., Bergueiro, J., Berman, F.W., Betharia, S., Bhattacharya, S., Biglar, M., Biswas, S., Black, A.T., Bloomhuff, A.B., Bloomquist, J.R., Bolduc, D.L., Bolger, P.M., Bolt, H.M., Bonventre, J.A., Borek, H.A., Borghoff, S.J., Borzelleca, J.F., Botelho, M.C., Boxall, A.B.A., Bradford, H., Brady, P.M., Broderick, M., Brown, D.A., Brown, J., Bruce, R.D., Brugge, D., Brugger, K.E., Bryant, M.A., Bucklin, M.H., Burns-Naas, L.A., Burr, S.A., Caballero, J.M., Cai, Z., Calabrese, E.J., Calvo, M., Cammack, J., Campbell, A., Canedy, T., Cantrell, F.L., Caquet, T., Carbonell, G., Carlson-Lynch, H., Carmichael, N., Carmo, H., Carr, D., Carrington, C.D., Carvalho, F., Carvalho, M., Casa-Resino, I. de la, Cash, L.J., Castranova, V., Cesnaitis, R., Chadwick, K.D., Chakraborty, P., Chan, P.P.K., Chang, S., Chapin, R.E., Chateauvieux, S., Chattopadhyay, A., Chaumot, A., Chen, G., Chen, X., Chesser, R.K., Chilakapati, J., Chojnacka, K., Chou, K., Christoforidis, J., Clark, A.K., Clewell, H.J., Clough, S.R., Coelho, P.C.S., Coggins, C.R.E., Cohen, S.M., Cole, S.D., Corcoran, G.B., Cornu, C., Corsini, E., Cory-Slechta, D.A., Costa, C., Costa, L.G., Costa, S., Covaci, A., Cowden, J., Cumpston, K.L., Curfman, E., Czerczak, S., Daam, M.A., Dahlstrom, D.L., Darracq, M.A., Darwich, A.S., Das, S.R., Davis, J.A., de la Casa Resino, I., de la Torre, A.H., de Lourdes Bastos, M., del Río, E., de Marcellus, S., Demers, P.A., de Peyster, A., Derakhshani, M., Desai, S.N., de San Andrés Larrea, M.I., Descotes, J., Devi, S.S., Devlin, J.J., de Voogt, P., Devriese, L., DeWoskin, R.S., de Zwart, D., Diederich, M., Dieter, H.H., Di Guardo, A., Đikić, D., Dincer, I., Dissanayake, V., DiZio, S.M., Dodd-Butera, T., Doke, D., Dorsey, R.M., Dougherty, M.M., Dourson, M.L., Drake, V.J., Duffus, J.H., Dumancas, G.G., Dumbacher, J.P., DuTeaux, S.B., Dydek, S.T., Dykens, J.A., Eagle, S.R., Eastmond, D.A., Easton, J.D., Eidemiller, B.J., Eisen, E.A., Emami, A., Emami, S., Embry, M.R., Emswiler, M.P., Erraguntla, N.K., Escribano, M., Espín, S., Estevan, C., Estévez, J., Etemad, L., Everson, G.W., Ewers, L.M., Fain, J.H., Fan, A.M., Farris, F.F., Farshchi, A., Fatoki, O.S., Feakes, D., Feasel, M., Fedoruk, M.J., Feitshans, I.L., Fent, G.M., Fernández-Tajes, J., Fernández, Á.J.G., Fernández, C., Fernández Rodríguez, M.D., Ferrari, B., Fidalgo, J., Fields, A., Finch, G.L., Finizio, A., Finnveden, G., Fitzgerald, L., Foroumadi, A., Fuentes, D., Gad, K., Gad, S.C., Gad, S.E., Gadagbui, B., Gammon, D.W., García-Fernández, A.J., García Gómez, M.C., Gardner, D.E., Garrard, A., Garric, J., Gautam, G., Geffard, O., Genter, M.B., Gevaart-Durkin, A., Ghafouri, N., Ghazali, A.R., Ghoreishi, K., Ghosh, B., Gilbert, S.G., Giordano, G., Giouleme, O., Gironés, M.C.L.R., Gobba, F., Goel, S., Gohari, A.R., Gohlke, J.M., Golbabaei, S., Gold, S.C., Gómez-López, V.M., Gómez-Ramírez, P., González-Canga, A., González, G.L., Goodman, J.E., Gordon, E., Gordon, T., Gorodetsky, R., Gray, J.P., Green, M.D., Greim, H., Griffiths, J.C., Groth, C.M., Guedes de Pinho, P., Gupta, N., Gupta, R.C., Gutiérrez, A.J., Guy, R.C., Haber, L.T., Hacatoglu, K., Hahn, K., Haines, J.A., Hakkinen, P.J., Hall, E.J., Hall, G.J., Hall, V.R., Hambright, K.D., Handler, J.A., Hansen, D.K., Hanson, K.M., Hanson, M., Hardison, L.S., Hardisson, A., Harper, S.L., Hartmann, A.C., Hartung, T., Hartwig, A., Hassani, S., Hatlelid, K.M., Hayes, A.W., Hayes, A.N., Heidari, M.R., Henderson, J., Henriksen, B., Hernández-Moreno, D., Hertzberg, R.C., Hesterberg, T., Heyndrickx, M., Hicks, D., Hikkaduwa Koralege, R.S., Hilburn, M.E., Hinderliter, P., Hines, E.P., Hirakawa, B., Hirata, C.M., Ho, S., Hobson, D.W., Hoffmann, S., Holloway, A.C., Holstege, C.P., Holstege, E., Hon, S.L., Honeycutt, M., Hong, S., Hoover, M.D., Hopf, N.B., Hopp, A.G., Horiguchi, H., Hosseini-Tabatabaei, A., Hosseini, A., Hostetler, M.A., Hsu, C.H., Huang, F.X., Hulla, J.E., Hultén, P., Hultin, M.L., Hurst, H.E., Iannucci, A., Inayat-Hussain, S.H., Inselman, A.L., Iskander, J., Jabbour, R.E., Jaberidoost, M., Jacobs, M., Jamei, M., Jamison, K.P., Janes, M., Janz, D.M., Jazayeri, S.B., Jenkins, A., Jiang, M., Jin, N., John, K., Jones, L., Jones, P.D., Jordan, S.A., Jurado, A.S., Kalapos, M.P., Kamrin, M.A., Kapp, R.W., Karami-Mohajeri, S., Karanth, S., Karimi, G., Katz, S.A., Kem, W.R., Kempegowda, P., Kennedy, G.L., Kester, J.E., Khaksar, M.R., Kharabaf, S., Khoobi, M., Kiersma, M.E., Kilpinen, J.M., Kim, D.H., Kim, S.T., Kimbrough, R.D., Klein, S.J., Knechtges, P.L., Knuckles, T.L., Knudsen, T.B., Korrapati, M.C., Koshlukova, S.E., Kovacic, P., Kraft, A., Krafts, K., Krishnan, P., Kruger, C.L., Kubic, A., Kulkarni, S., Kwok, E.S.C., Laffon, B., Lagadic, L., Lambert, C.E., Landolph, J.R., Lange, R.W., Lank, P., Lari, P., Lasley, W., Lawana, V., Lazo, C.R., Ledrich, M.-L., Le Goff, F., Lein, P.J., Leung, H.-W., Leung, Y.L., Lewandowski, T.A., Li, X., Liesivuori, J., Lim, L., Limaye, P., Lin, H.H., Lin, S.C., Litovitz, T., Liu, F., Liu, J., Lloyd-Smith, M., Lo, J.C.Y., Loccisano, A.E., Logan, P., López, S., Lord-Garcia, J., Lotti, M., Luschützky, E., Mahdaviani, P., Maier, A., Makhaeva, G.F., Malátová, I., Malekirad, A.A., Manayi, A., Mangas, I., Mangino, M., Mangipudy, R.S., Maples, R.D., Marcel, B.J., Marigómez, I., Marraffa, J.M., Martínez-López, E., Mathews, S.M., Maxim, L.D., Maxwell-Stuart, P.G., Mayor, A., McClane, B.A., McCoole, M.D., McCormick, D.B., McGregor, D., McKee, J.M., McMartin, K., Meek, B., Megharaj, M., Mehendale, H.M., Mehrpour, O., Mendes, A., Méndez, J., Menn, F.-M., Meyer, S.A., Michalak, I., Míguez-Santiyán, M.P., Mikulewicz, M., Milanez, S., Mileson, B.E., Miller, G.W., Miller, S.J., Miller, S.M., Millner, G.C., Minarchick, V.C., Miracle, A.L., Mirajkar, N.S., Mirkes, P.E., Mitra, M.S., Mody, V., Mogl, S., Mohammadirad, A., Mojica, E.-R.E., Molander, L., Molina López, A.M., Momen-Heravi, F., Montague, P., Monteiro, J.P., Monticelli, F., Morceau, F., Moreno, M., Morgan, B.W., Mortensen, S.R., Moser, V.C., Moshiri, M., Mostafalou, S., Moyer, R.A., Mumy, K.L., Munday, R., Murdianti, B.S., Murray, A., Murray, T.M., Murta, T.L., Nadri, H., Naidu, R., Naile, J.E., Naistat, D.M., Nakajima, T., Nalliah, R.E., Nance, P., Nathan, S., Navarro, L., Navas, I.M., Nelson, L.S., Nerin, C., Newsted, J., Nikfar, S., Nili-Ahmadabadi, A., Nobay, F., Nony, P., Nurkiewicz, T.R., Oi, M., Okoro, H.K., Oliveira, P.A., Olsen, L.R., Oropesa Jiménez, A.L., Othumpangat, S., Pablos, M.V., Pakulska, D., Pakzad, M., Pallasch, E.M., Pamies, D., Parihar, H.S., Parmar, M.S., Parod, R.J., Paschos, P., Patterson, J., Patterson, T.J., Patterson, T.A., Paulo Teixeira, J., Pawlaczyk, A., Pearson, M.A., Pellerano, M.B., Pellizzato, F., Perales, C.M., Peredy, T., Pereira, J., Pérez-López, M., Peri, R., Persad, A.S., Persson, H., Perwaiz, S., Peterson, M.K., Pham, P.J., Pham, T., Philip, B.K., Pichery, C., Pickett, A.J., Piña, B., Pinkerton, K.E., Pleus, R.C., Podder, S., Poirier, M.C., Pomerleau, A.C., Pope, C., Posthuma, L., Potting, J., Pournourmohammadi, S., Pravasi, S.D., Preston, R.J., Prusakov, P.A., Punja, M., Puran, A.C., Purcell, M.M., Qian, L., Qozi, M., Quintana, P.J.E., Rabiei, M., Radulovic, L.L., Rahmani, N., Rajabi, M., Raman, P., Ramasahayam, S., Ramos-Peralonso, M.J., Rankin, G.O., Rao, C.V., Rao, P.S., Rashedinia, M., Rath, A.D., Ray, D.E., Ray, S.D., Reed, N.R., Remião, F., Rezaee, R., Rezvanfar, M.A., Rezvani, N., Rhomberg, L.R., Riar, N.K., Rice, G., Richardson, J.R., Richardson, R.J., Richter, P., Rider, G., Rivera, H.L., Robbens, J., Roberts, D.J., Roberts, L.G., Robinson, P.J., Robles, H., Rodgers, B.E., Rodgers, K., Rodriguez, Y.R., Rodriguez Fernández, C., Roede, J.R., Rogawski, M.A., Rojo, L., Romano, J.A., Rose, S.R., Rosen, M.A., Rossol, M., Rostami–Hodjegan, A., Rourke, J.L., Roy, R., Roy, S.S., Rozman, K.K., Rubin, A.L., Rubio, C., Ruch, R.J., Rumbeiha, W.K., Rushton, W., Sabzevari, O., Saeedi, M., Saeid, A., Saeidnia, S., Saghir, S.A., Saili, K.S., Salem, H., Salvago, M.R. Moyano, Salvatore, J.R., San Andrés Larrea, M.D., San Andrés Larrea, M.I., Sarazan, R.D., Sardari, S., Sasaki, T., Sawant, S.P., Schaeffer, V., Schep, L.J., Schlesinger, R.B., Schneider, S.M., Schreffler, S.M., Schultz, M.M., Schwartz, M., Schwela, D., Scott, A.L., Scott, B.R., Scribner, K., Seabury, R.W., Seco, B., Seeley, M., Seifert, J., Sellamuthu, R., Serex, T.L., Sexton, K., Shadnia, S., Shafiee, A., Shah, I., Shankar, K., Sheets, L.P., Sheppard, L., Shiotsuka, R.N., Shirley, S., Shojaei Saadi, H.A., Sibbald, K.N., Sidell, F.R., Siegrist, M., Simmons, J.E., Sinal, C.J., Singh, P., Skoglund, R., Skonberg, C., Slaughter, R.J., Sledge, C.L., Slothower, J.D., Smith, M., Smith, M.T., Snider, D.B., Snyman, R.G., Sobanska, M., Sogorb, M.Á., Soler-Rodríguez, F., Solgi, R., Solomon, K.R., Somanathan, R., Sonawane, B.R., Song, X., Soni, M.G., Sorensen, J., Soucy, N.V., Southard, R.J., Spainhour, C.B., Spencer, P.S., Spiller, H.A., Spoelhof, B., Stanard, B., Stanek, L.W., Stapleton, P.A., Stedeford, T., Steidl-Nichols, J., Stephens, M., Steyn, N.P., Stickney, J., Stohs, S.J., Stone, D., Stool, D., Stork, C.M., Strohm, B., Stromberg, P.E., Sullivan, D.W., Sullivan, M.R., Sultatos, L.G., Suryanarayanan, A., Syed, I., Szabo, D.T., Szynkowska, M.I., Takacs, Z., Talaska, G., Talbot, P., Tanguay, R.L., Tarazona, J.V., Teixeira, J.P., Temple, N.J., Temple, W.A., Tena, A., Teuschler, L.K., Thackaberry, E.A., Thakore, K.N., Theodorakis, C., Thompson, R.E., Thornton, S.L., Ting, D., Tirmenstein, M.A., Touwaide, A., Towne, T.G., Traven, S.A., Tritscher, A., Troendle, M., Trosko, J.E., Tsai, W.-T., Tsai-Turton, M., Tsatsakis, A., Tsitsimpikou, C., Tsubura, A., Tsuda, T., Tyl, R.W., Udarbe Zamora, E.M., Utell, M.J., Vahabzadeh, M., Vaidya, V.S., Valdiglesias, V., Valentovic, M.A., Valerio, L.G., Vales, T., Vandenberg, L.N., van den Brink, P.J., van der Kolk, J., Van Vleet, T.R., van Vliet, E., Varga, J., Venkateswarlu, K., Verslycke, T., Versonnen, B., Verstraete, K., Vighi, M., Vilanova, E., Vincent, L., Vincent, M., Visser, R., Volger, B., von Stackelberg, K., Vulimiri, S.V., Wahl, M., Walker, N.J., Walker, T.D., Wallace, D.R., Wang, C., Wang, G.S., Wanna-Nakamura, S.C., Watson, R.E., Wattenberg, E.V., Wax, P.M., Weaver, J.A., Webber, N.R., Weber, J.A., Weber, L.P., Weinrich, A.J., Weiss, B., Wennberg, A., Wernke, M.J., Weston, A., Wexler, P., White, L.D., Whittaker, M.H., Wiedenfeld, H., Wiegand, T.J., Wikoff, D.S., Wild, C.P., Will, Y., Willett, C., Willhite, C.C., Willis, A., Willis, K., Wills, B.K., Wilson, B.W., Wittliff, J.L., Wojcinski, Z.W., Wolfe, M.S., Wood, C.S., Woodall, G.M., Woolley, A., Xia, M., Ximba, B.J., Yan, B., Yanagiba, Y., Yang, D., Yang, N., Yoon, M., Yorifuji, T., Yoshizawa, K., Young, R.A., Zamor, R.M., and Zhao, Q.J.

Published
2014
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34. Treatment of Methanol Poisoning With Intravenous 4-Methylpyrazole

Author

Burns, M.J., Graudins, A., Aaron, C.K., McMartin, K., and Brent, J.

Abstract

Treatment of human methanol poisoning with the alcohol dehydrogenase inhibitor, 4-methylpyrazole (fomepizole), has not been previously described. We report the clinical and toxicokinetic data of a patient with methanol poisoning who was treated with fomepizole. Formic acid levels remained undetectable during fomepizole treatment, the toxic effects of methanol were prevented, and the patient made a full recovery. [Burns MJ, Graudins A, Aaron CK, McMartin K, Brent J: Treatment of methanol poisoning with intravenous 4-methylpyrazole. Ann Emerg Med December 1997;30:829-832.]

Published
1997
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35. Differential effects of acute ethanol on urinary excretion of folate derivatives in the rat.

Author

Eisenga, B H, Collins, T D, and McMartin, K E

Abstract

The ethanol-induced increase in the urinary excretion of folate has been determined to be both a time- and dose-dependent phenomenon and it has been speculated that this loss may enhance the development of folate deficiency. However, ethanol has only a minor effect on the renal clearance of exogenously administered [3H]folic acid [3H]PteGlu) in relation to that of inulin. To clarify this variable effect of ethanol, male Sprague-Dawley rats were given four consecutive hourly doses of ethanol at 1 g/kg and placed in metabolic chambers for collection of urine. At 5 hr, [3H]PteGlu was administered and urine samples were collected for 1 hr. At 6 hr, rats were sacrificed with collection of plasma, liver and kidney samples. A significant increase in the urinary excretion of endogenous folates occurred in ethanol-treated rats at both the 4-5- and 5- to 6-hr time periods, but no significant increase in 3H-labeled derivatives was noted in ethanol-treated rats. Subsequent high pressure liquid chromatographic analysis of urine extracts showed that the predominant 3H-labeled PteGlu metabolites were [3H]-5-formimino-H4PteGlu and the formyl-tetrahydrofolates, whereas the major endogenous form was 5-CH3-H4PteGlu. Ethanol administration increased significantly the excretion of the methyl derivative, with minor effects on the other folate forms. These results suggest that there is a selective effect of ethanol on the urinary excretion of specific folate derivatives. Also, inasmuch as no 5-formimino-H4-PteGlu was detected in the plasma, the rodent kidney appears to have the capacity for uptake and metabolism of filtered PteGlu.

Published
1989

49. Fomepizole for the treatment of methanol poisoning.

Author

Brent, Jeffrey, McMartin, Kenneth, Phillips, Scott, Aaron, Cynthia, Kulig, Ken, Brent, J, McMartin, K, Phillips, S, Aaron, C, Kulig, K, and Methylpyrazole for Toxic Alcohols Study Group

Subjects
*POISONING, *METHANOL, *ALCOHOL dehydrogenase, *TOXICOLOGY, *CHEMICAL inhibitors, *THERAPEUTICS
Abstract

Background: Methanol poisoning may result in metabolic acidosis, blindness, and death. The inhibition of alcohol dehydrogenase is fundamental to the treatment of methanol poisoning. We performed a multicenter study to evaluate fomepizole, an inhibitor of alcohol dehydrogenase, in the treatment of patients with methanol poisoning.Methods: We administered intravenous fomepizole to 11 consecutive patients who presented with methanol poisoning at a participating center. Serial clinical and laboratory studies, including measurements of plasma formic acid and fomepizole, were performed. The outcomes measured were the preservation of visual acuity, the resolution of metabolic acidosis, the inhibition of formic acid production, the achievment of therapeutic plasma concentrations of fomepizole with the dosing regimen, residual illness or disability, and death.Results: Plasma formic acid concentrations were detectable in eight patients, and these concentrations were closely correlated with the initial arterial pH values (r=0.92, P<0.001). In response to fomepizole, plasma formic acid concentrations fell and metabolic abnormalities resolved in all patients. Nine patients survived. Seven patients initially had visual abnormalities, but at the end of the trial no surviving patient had any detectable visual deficits related to methanol poisoning. Fomepizole had few adverse effects. The two patients who died had anoxic brain injury that was present at the time of enrollment. During treatment, methanol had an elimination half-life of 54 hours.Conclusions: Fomepizole appears to be safe and effective in the treatment of methanol poisoning. [ABSTRACT FROM AUTHOR]

Published
2001
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