False-positive urine beta-HCG in a woman with a tubo-ovarian abscess.

Modern urine beta-human chorionic gonadotropin (HCG) assays that use enzyme-linked immunosorbent assay (ELISA) technology are sensitive and specific for diagnosing pregnancy, both intrauterine and ectopic, and have become indispensable to the practice of Emergency Medicine. A urine HCG test is often relied on by the Emergency Physician as a critical component in the diagnostic regimen of a patient with a possible ectopic pregnancy. We report a case of a false-positive urine beta-HCG test in a patient with a ruptured tubo-ovarian abscess. Though false-positive pregnancy tests with tubo-ovarian abscesses have previously been reported with older methods of HCG detection, we believe that this is the first case where the pregnancy test was the modern ELISA type. The mechanism for the false-positive reaction in this case is unknown, but time may show that the ELISA test kit, like its predecessors, may occasionally give a false-positive reaction in this class of patients.

Defining, identifying, and measuring error in emergency medicine.

The findings of a consensus committee created to address the definition, measurement, and identification of error in emergency medicine (EM) are presented. The literature of error measurement in medicine is also reviewed and analyzed. The consensus committee recommended adopting a standard set of terms found in the medical error literature. Issues surrounding error identification are discussed. The pros and cons of mandatory reporting, voluntary reporting, and surveillance systems are addressed, as is error reporting at the clinician, hospital, and oversight group levels. Committee recommendations are made regarding the initial steps EM should take to address error. The establishment of patient safety boards at each institution is also recommended.

Emergency medicine can play a leadership role in enterprise-wide clinical information systems.

At many institutions, the department of emergency medicine is uniquely suited to a leadership role in the deployment of new clinical decision support systems (computer systems that support clinical practice). Many factors favor such a leadership role, including institutional politics, organizational structure, extent of local control, clinician solidarity, openness to change, departmental size and scale, and willingness to take risks. Such a role should be undertaken in partnership with the institution's information services (IS) department, and a clear understanding of goals and responsibilities will facilitate such a partnership. A leadership position with respect to new information systems entails a certain risk, but the potential benefit to an emergency department in today's competitive environment is substantial. The authors' experience with one such collaborative development project is presented.

Computers and connectivity in Illinois emergency departments.

UNLABELLED: Although the Internet has been described as "ubiquitous," little is known about the extent to which physicians have access to the Internet while providing clinical care. OBJECTIVE: To assess the extent of Internet connectivity within the clinical area of every ED within the state of Illinois. METHODS: This was a prospective observational study. Each Illinois ED listed in a published directory was called by telephone, and a responsible party was identified to provide information regarding the type and size of the ED, patient demographics, the types of personal computers (PCs) available in the ED (if any), the types of operating systems used, the availability of access to the World Wide Web (Web), and the highest speed at which an Internet connection could be established. Responses regarding the presence and types of PCs and the types of operating systems used were assessed using one-factor chi-square. Univariate and multivariate predictors of the type of PC used, the presence or absence of Web access, and the highest speed of Internet access were evaluated using optimal discriminant analysis and nonlinear classification tree analysis, respectively. RESULTS: One hundred ninety-eight of the 199 EDs in the state of Illinois (99.5%) completed the survey. Of the responding EDs, 50.5% had PCs, but only 17.6% had Web access. When Web access was available, it was most often available through a high-speed Internet connection that was faster than a dial-up modem. Most departments (68.1%) with PCs used the Windows 95 or Windows 98 operating systems. A majority (62.5%) used the Netscape browser exclusively. Larger EDs (more than six ED beds) in rural or suburban areas were more likely to have a PC compared with smaller EDs (six or fewer beds). Large EDs (more than 12 ED beds) in private tertiary care or academic hospitals were most likely to have Web access. CONCLUSIONS: Although half of Illinois EDs have PCs, only one in six has access to the Internet; thus, most emergency physicians do not have ready access to the Web from the site where they deliver clinical care.

Selective inhibition of phospholipases by atiprimod, a macrophage targeting antiarthritic compound.

Azaspiranes are cationic amphiphilic compounds that are active in a number of models of autoimmune disease and transplantation. Repeated administration of cationic amphiphiles induces phospholipid accumulation in a variety of species. The present study was conducted to explore the mechanism of phospholipid accumulation in rats caused by treatment with the novel azaspirane, SK&F 106615 (atiprimod). Atiprimod inhibited the activities of partially purified phospholipases A(2) and C, but not D, in a noncompetitive manner in vitro. Treatment of rats for 28 days with 10 mg/kg/day of atiprimod increased the contents of arachidonate-containing molecular species within plasmalogen subclasses of hepatic phosphatidylcholine and phosphatidylethanolamine. In contrast, diacyl-linked species were not affected, indicating a selective effect upon an hepatic plasmalogen-selective phospholipase A(2). Taken together, the data suggest that the beneficial effects of atiprimod in autoimmune diseases may involve inhibition of phospholipase A(2) and C activities. Further, the data suggest that atiprimod is a selective inhibitor of plasmalogen-selective phospholipase A(2) in vivo.

Atiprimod (SK&F 106615), a novel macrophage targeting agent, enhances alveolar macrophage candidacidal activity and is not immunosuppressive in Candida-infected mice.

Azaspiranes are novel macrophage-targeting agents with activity in preclinical animal models of autoimmune disease and transplantation. The purpose of this work was to determine the effects of atiprimod (SK&F 106615), an azaspirane being developed for the treatment of rheumatoid arthritis, on rat pulmonary alveolar macrophage (AM) function and immunocompetance in Candida-infected mice. AM from rats treated with 20 mg/kg/day of atiprimod for 15 days demonstrated enhanced killing of Candida albicans ex vivo. Concentration-dependent increases in candidacidal activity were also observed as early as one hour after exposure in vitro in AM from untreated normal rats. Treatment of AM with atiprimod in vitro did not increase particulate-stimulated superoxide production or phagocytosis of Candida but decreased their ability to concentrate acridine orange, indicating an increase in lysosomal pH. Increased candidacidal activity was inhibited by superoxide dismutase and catalase, suggesting a role for reactive oxygen intermediates (ROI). Atiprimod also increased free radical-mediated killing of Candida in the presence of H2O2, iron and iodide in a cell-free system. These findings indicated that treatment with atiprimod increased the candidacidal activity of rat AM in a free radical-dependent manner. The data also suggested that atiprimod did not increase ROI production by AM, but rather increased the efficiency of radical-mediated killing. This increase may be caused by cyclization of atiprimod, facilitating electron transfer and peroxidation of lipid membranes. In vivo studies in Candida-infected CBA mice showed that atiprimod (10 mg/kg/day), did not compromise immune function in the infected mice and could be differentiated from prototypical immunosuppressive compounds used for treatment of autoimmune diseases.

Effect of aging on mixed-function oxidation and conjugation by isolated perfused rat livers.

Aging is known to decrease hepatic cytochrome P450 content in rats. However, limited information is available on the effects of aging on mixed-function oxidation and conjugation in intact liver. The purpose of these studies was to determine the effects of aging on oxidation and conjugation of p-nitrophenol (pNP) in perfused livers from male Sprague-Dawley rats. Livers from senescent (22-24 months) or young adult (3-6 months) rats were perfused in a nonrecirculating hemoglobin-free system and supplemented with pNP (60 microM). Glucuronide and sulfate conjugates of the oxidation product, 4-nitrocatechol, in effluent perfusate were cleaved enzymatically and 4-nitrocatechol was determined colorimetrically. Rates of 4-nitrocatechol production were decreased in senescent compared with young adult rats (0.67 +/- 0.14 vs 0.92 +/- 0.15 micromol/g/hr). However, the rates of oxidation of pNP in microsomes from senescent rats were similar to those in young adult rats. Hepatic malate content was decreased approximately 50% in livers from senescent compared with young adult rats in the presence and absence of pNP, suggesting that movement of reducing equivalents from the mitochondria to the cytosol, and thus cytosolic NADPH supply, may have been diminished by senescence. The rates of conjugation of 60 microM pNP in perfused livers from senescent rats were similar to those in young adult rats, but Km and Vmax values of microsomal 4-nitrocatechol glucuronyltransferase were about 2.5- and 1.6-fold higher, respectively, in livers from senescent compared with young adult rats. Hepatic glycogen content was about 50% lower in livers from senescent compared with young adult rats, but the contents of UDP-glucose and UDP glucuronic acid were similar between the two groups. Taken together, the data are consistent with the hypothesis that rates of mixed-function oxidation are decreased in intact livers from senescent compared with young adult rats, due possibly to age-related changes in cofactor supplies. Glucuronidation of low, but not high, concentrations of substrates may be affected by age-related changes in Km and Vmax values of microsomal glucuronyltransferase.

Toxic psychosis: an unusual presentation of propranolol intoxication.

Timely diagnosis of acute propranolol intoxication requires a high index of suspicion and a knowledge of the multiple ways in which these patients may present to the emergency department. We report a case of severe propranolol intoxication that presented as an acute psychotic episode preceding cardiovascular decompensation and seizures by several hours. Though acute reversible psychosis has been appreciated after initiating or increasing propranolol dosage therapeutically, this association has not been reported in the literature regarding beta blocker overdose or intoxication. Propranolol psychosis and several other pertinent aspects of this case are discussed.

General ophthalmologic examination.

Caring for patients with eye emergencies will always challenge even the most experienced emergency clinician. The threat of loss of sight is anxiety provoking for patients and requires the physician to act in an organized and expeditious manner. By avoiding these pitfalls and examining each patient in a systematic and comprehensive fashion, the physician can ensure the best possible outcome. The ensuing articles describe the approach to diagnosing and treating significant eye emergencies in greater detail.

Acute pulmonary embolism. Aggressive therapy with anticoagulants and thrombolytics.

Patients with acute pulmonary embolism are at risk for early death or chronic morbidity. Appropriate therapy can dramatically reduce the incidence of both. Oxygen and heparin therapy should be started as soon as the diagnosis is suspected. The condition of a hypotensive patient with right ventricular overload from acute pulmonary embolism usually is made worse by a fluid challenge; hypotension may be relieved by preload reduction or even by gentle diuresis. Norepinephrine (Levophed), isoproterenol hydrochloride (Isuprel), and epinephrine are the pressor agents of choice. Immediate thrombolysis is the standard of care for any patient with significant hypoxemia or hypotension due to proven pulmonary embolism. Beyond this, the potential benefit of using thrombolytic agents should be considered routinely for every patient with proven pulmonary embolism. Surgical embolectomy is useful for unstable pulmonary embolism when there are absolute contraindications to thrombolysis or when thrombolytic therapy fails. Empirical use of thrombolysis may be considered as a last-ditch effort for a critically ill patient when there is a high clinical suspicion of pulmonary embolism. Standard closed-chest cardiopulmonary resuscitation is ineffective when the pulmonary circulation is obstructed by thrombus. Emergency thoracotomy or femorofemoral cardiopulmonary bypass is appropriately used in patients with full cardiac arrest from pulmonary embolism.

Chronic pulmonary embolism. Often misdiagnosed, difficult to treat.

Chronic thromboembolic pulmonary hypertension with cor pulmonale is an extremely debilitating disease that (1) is more common than generally recognized, (2) is often misdiagnosed, and (3) is difficult to treat. When a patient has persistent exertional dyspnea with no obvious cause, a ventilation-perfusion scan, echocardiography, and (if indicated) pulmonary angiography should be done. Prevention is especially important because by the time a patient is symptomatic, the disease is already far advanced and hemodynamic reserves are greatly reduced. Prevention of recurrence mandates lifetime anticoagulation and placement of a vena cava filter. The only effective treatment is pulmonary endarterectomy, which is being performed at an increasing number of specialty centers across the United States.

Hepatobiliary function in senescent male Sprague-Dawley rats.

The purpose of these studies was to investigate intrahepatic changes underlying age-related decreases in bile flow by evaluating the effects of aging on bile acid-dependent and -independent flow, canalicular versus ductular flow and hepatic tight junction permeability. The isolated perfused liver was used to assess age-related changes in intrinsic hepatobiliary function without the complications of extrahepatic factors such as circulating hormones or hemodynamics. Livers from young adults (3 to 6 mo old) or senescent (22 to 26 mo old) male Sprague-Dawley rats were isolated and perfused in a nonrecirculating, hemoglobin-free system to assess oxygen uptake, bile acid-dependent and -independent bile flow, bile acid uptake, carbon 14-labeled erythritol clearance as a measure of canalicular flow, tight junction permeability and transcellular transport into bile. Rates of oxygen uptake by livers from senescent rats were significantly lower than those of young adults (75 +/- 8 mumol/gm/hr vs. 121 +/- 5 mumol/gm/hr). Age-related decreases in total bile flow were observed and were associated with similar reductions in 14C-erythritol clearance suggestive of decreased canalicular bile flow. Bile acid-dependent and -independent flow was decreased by 50% and 60%, respectively, in isolated perfused livers from senescent rats. Hepatocellular uptake of taurocholate and rates of bile acid excretion also were about 50% lower in senescent than in young adult rats. Tight junction permeability and transcellular transport were assessed by monitoring appearance of tritiated inulin and horseradish peroxidase in bile after bolus injections of these compounds through the portal vein. Tritiated inulin appearance in bile was decreased slightly in senescent compared with young rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of hepatobiliary function in vivo and ex vivo in the rat.

Many xenobiotics cause hepatobiliary toxicity and cholestasis in the rat. Initial assessment of hepatobiliary damage in rats can be accomplished by measuring serum concentrations of bile acids and bilirubin, serum activities of liver-associated enzymes such as 5'-nucleotidase, alkaline phosphatase, gamma-glutamyltranspeptidase, and plasma clearances of dyes [e.g., bromosulfophthalein (BSP)] excreted primarily through the bile. More detailed evaluation of hepatobiliary disturbances involves cannulation of the bile duct of anesthetized rats and subsequent measurement of rates of bile flow, bile acid excretion, and bile composition. Canalicular bile flow can be estimated from clearances of nonmetabolized sugars (i.e., erythritol) which enter bile via paracellular transport. Tight junction permeability also can be assessed by either biliary excretion of such a marker as horseradish peroxidase or sucrose following portal vein infusion or via retrograde biliary infusion. Subsequent morphologic evaluation of the liver provides information on damage to cells which may contribute to hepatobiliary dysfunction (i.e., bile duct obstruction). Isolated perfused livers offer the ability to measure all of the above mentioned parameters as well as to make a more accurate determination of the effects of xenobiotics on bile acid-dependent and -independent bile flow. A good example of the advantage of combining techniques as well as following complete time courses of changes in hepatobiliary function is provided by using studies of alpha-naphthylisothiocyanate-induced hepatotoxicity.

Cholestatic potentials of alpha-naphthylisothiocyanate (ANIT) and beta-naphthylisothiocyanate (BNIT) in the isolated perfused rat liver.

Previous studies in rats have shown that a single oral dose of alpha-naphthylisothiocyanate (ANIT), but not the regioisomer beta-naphthylisothiocyanate (BNIT), results in intrahepatic cholestasis. The present studies were designed to evaluate the intrinsic cholestatic potential of ANIT and BNIT in the isolated perfused rat liver. Livers from male Sprague-Dawley rats (300-450 g) were isolated and perfused with Krebs-Henseleit buffer supplemented with 50 microM taurocholate and ANIT or BNIT (0, 5, 15 or 50 microM). Rates of bile flow, bile acid uptake and bile acid excretion were monitored for up to 70 min. Permeability of tight junctions also was evaluated. At concentrations of 5 microM, neither ANIT nor BNIT altered hepatobiliary function or tight junction permeability. In contrast, perfusion with 50 microM ANIT or BNIT for 35 min resulted in decreases in bile flow rates of 19 +/- 8 and 13 +/- 4%, respectively. After 70 min of perfusion with ANIT or BNIT, rates of bile flow were decreased by 78 +/- 5 and 71 +/- 4%, respectively. Bile acid excretion also was decreased following perfusion with 50 microM ANIT or BNIT. Perfusion with 50 microM ANIT or BNIT decreased bile acid uptake by 51 +/- 13 and 46 +/- 6%, respectively, at 60 min. Bile/plasma (B/P) ratios of [3H]sucrose were not affected by ANIT or BNIT at any time during perfusion, indicating that changes in bile flow and bile acid excretion in the isolated perfused liver were not associated with increased hepatocyte tight junction permeability. These data demonstrate that the direct portal infusion of a 50 microM concentration of either ANIT or BNIT produced marked decreases in bile flow, indicating that these isomers have a comparable intrinsic cholestatic potential in the isolated perfused liver.

Evidence that catalase is a major pathway of ethanol oxidation in vivo: dose-response studies in deer mice using methanol as a selective substrate.

Recently, it was demonstrated that 4-methylpyrazole was not only an inhibitor of alcohol dehydrogenase but also caused competitive inhibition of fatty acyl-CoA synthetase, the enzyme which activates fatty acids (B. U. Bradford, D. T. Forman, and R. G. Thurman, 1993, Mol. Pharmacol. 43, 115-119). Rates of catalase-dependent alcohol metabolism were decreased in alcohol dehydrogenase-negative (ADH-) deer mice because the H2O2 supply for catalase via peroxisomal fatty acid oxidation was inhibited due to substrate limitation. In light of these findings it became necessary to reevaluate the role of catalase and alcohol dehydrogenase in alcohol metabolism. In this study, methanol, a selective substrate for catalase in rodents, was compared with ethanol. Rates of ethanol and methanol metabolism were studied in vivo at blood alcohol levels ranging from 50 to 500 mg/dl. In the ADH- deer mouse, rates of methanol and ethanol metabolism increased when alcohol was elevated from 0 to 100 mg/dl and were maximal at values around 6-8 mmol/kg/h (half-maximal rates were observed at blood alcohol levels around 50 mg/dl). In the ADH+ deer mouse, rates of ethanol metabolism increased to values around 9 mmol/kg/h at 100 mg/dl and remained constant at blood levels up to 500 mg/dl. In contrast, rates of methanol metabolism increased to values of only 5 mmol/kg/h at levels of 100 mg/dl (the half-maximal rate was about 2.5 mmol/kg/h at 50 mg/dl) followed by a steady increase to 9 mmol/kg/h as the blood level was increased from 100 to 500 mg/dl (the half-maximal rate for this second component was around 6 mmol/kg/h at 300 mg/dl). Rates of methanol uptake were 50 +/- 4 nmol/min/mg protein in 10,000g pellets from ADH- deer mouse livers; however, methanol was not metabolized by isolated microsomes. The catalase inhibitor aminotriazole decreased ethanol and methanol metabolism 75% in ADH- deer mice. Further, olive oil, which is rich in oleate, increased methanol metabolism from 7 to 11.5 mmol/kg/h. This stimulation was blocked by fructose, which diminishes ATP and decreases H2O2 supply. In the ADH+ deer mouse, fructose (2 g/kg) stimulated ethanol metabolism as expected; however, inhibition of both ethanol and methanol metabolism was observed with higher doses of fructose (10 g/kg). Taken together, these data support the hypothesis that catalase is the predominant pathway for alcohol metabolism in the ADH- deer mouse. The contribution of catalase was about 50% in the ADH+ mutant at low doses of ethanol and approached 100% as the alcohol concentration was elevated.

Temporal relationship of changes in hepatobiliary function and morphology in rats following alpha-naphthylisothiocyanate (ANIT) administration.

These studies were designed to evaluate ANIT-induced changes in both hepatobiliary function and morphology during the onset, progression, and recovery of ANIT-induced cholestasis. A single oral dose of 150 mg/kg of ANIT or vehicle was administered by gavage to male Sprague-Dawley rats and hepatobiliary structure and function were evaluated 16, 24, 48, 72, and 168 hr later. Increased hepatocellular tight junction permeability, increased serum bile acids, and decreased bile acid excretion were observed 16 hr after ANIT administration. At 24 hr, bile flow was decreased in ANIT-treated rats, an effect accompanied by increased tight junction permeability, decreased bile acid excretion, and decreased erythritol clearance (estimate of canalicular flow). In addition, scattered small loci of hepatocellular necrosis accompanied by an inflammatory cell response were observed in ANIT-treated rats at this time, with no microscopic evidence of bile duct obstruction (BDO). These data suggest that the onset of ANIT-induced cholestasis was associated with hepatocanalicular changes and not BDO. In contrast, at 48 and 72 hr after ANIT treatment, cholestasis was more profound and was accompanied by mild hepatocellular necrosis and widespread BDO. Hepatocyte tight junction permeability in ANIT-treated rats was not different from controls at 72 hr. These data suggest that the pathogenesis of ANIT-induced cholestasis is biphasic; the onset of cholestasis appears to be associated with changes in hepatocanalicular function and increased tight junction permeability whereas the later and more profound phase of cholestasis appears to be related to a combination of BDO and hepatocellular dysfunction. The time course of biochemical and morphologic changes following ANIT treatment further suggests that the pathophysiologic changes during the onset or initiation phase of cholestasis differ from those involved in the later and more profound phase of ANIT-induced cholestasis.

Chronic ethanol treatment induces H2O2 production selectively in pericentral regions of the liver lobule.

Chronic treatment with ethanol damages pericentral regions of the liver selectively, and reactive oxygen species such as H2O2 may be involved in the mechanism of hepatotoxicity. To test this idea, the effect of chronic treatment with ethanol on rates of H2O2 production was measured in tissue cylinders isolated from periportal and pericentral regions of livers from ethanol-treated rats. Rates of hydrogen peroxide production, assessed from the oxidation of methanol to formaldehyde by catalase-H2O2, were similar in tissue cylinders isolated from periportal regions in control and ethanol-treated rats. In contrast, rates of H2O2 production were over 4-fold higher in tissue isolated from pericentral regions of livers from ethanol-treated than control animals (1.7 +/- 0.5 vs. 0.4 +/- 0.3 nmol/min/mg protein, respectively). Rates of H2O2-generating acyl CoA oxidase activity were equivalent in tissue cylinders from periportal regions of livers from both groups (approximately 2 nmol/min/mg protein), but were over 2-fold higher in tissue cylinders from pericentral regions of livers from ethanol-treated rats than from controls. In contrast, catalase activity was increased nearly 2-fold in homogenates from both periportal and pericentral regions by ethanol treatment while glutathione peroxidase activity was decreased significantly in both regions. These data demonstrate that ethanol increases H2O2 generation in pericentral regions of the liver lobule in part by elevating rates of peroxisomal beta-oxidation of acyl CoA compounds and are consistent with the hypothesis that local increases in H2O2 production may be involved in the mechanism of ethanol-induced hepatotoxicity.

Transient activation of hepatic glycogenolysis by thrombin in perfused rat livers.

Thrombin, a peptide with native protease activity, caused a rapid (less than 1 min) increase in glycogenolysis of about 30%, assessed from rates of production of glucose+lactate+pyruvate, and in oxygen uptake in perfused rat liver. These increases were followed by a rapid return to basal values within 5 min. The effect of thrombin on glycogenolysis was dose-dependent and was maximal at perfusate concentrations around 1 U/ml. Interestingly, the effect of thrombin on glycogenolysis could be elicited only once in any given liver. The activation of glycogenolysis by thrombin was diminished nearly 50% by prior infusion of the protease inhibitor, diisopropyl fluorophosphate (10 microM), and over 90% when thrombin was treated with diisopropyl fluorophosphate prior to infusion. The stimulation of glycogenolysis by thrombin could be detected in isolated hepatocytes or in livers stored for 24 h in cold Euro-Collins solution, a treatment which destroys endothelial cells. Further, thrombin stimulated production of prostaglandin D2 from arachidonic acid in cultured hepatic endothelial but not Kupffer cells. The effect of thrombin on carbohydrate output was also blocked by a phospholipase A2 inhibitor (quinacrine, 50 microM) and by an inhibitor of the cyclooxygenase (indomethacin, 20 microM), suggesting the involvement of cyclooxygenase in the mechanism of action of thrombin. In support of this idea, the transient kinetics of stimulation of glycogenolysis by thrombin and arachidonic acid was nearly identical to release of thromboxane B2 (80-420 pg/ml) and prostaglandin D2 (300-900 pg/ml) from the perfused liver. Further, a second addition of thrombin failed to increase thromboxane and prostaglandin D2 release as well as carbohydrate production, supporting a causal link between these phenomena. Taken together, these data support the hypothesis that thrombin interacts with receptors in the liver, possibly on endothelial cells, leading to activation of phospholipase A2 and subsequent transient production of prostaglandins and thromboxanes. These mediators subsequently interact with receptors on parenchymal cells, leading to a transient stimulation of glycogenolysis.

Oxidoreduction of butanol in deermice (Peromyscus maniculatus) lacking hepatic cytosolic alcohol dehydrogenase.

In view of conflicting information in the literature regarding enzyme systems responsible for alcohol oxidation in deermice previously reported to lack hepatic alcohol dehydrogenase (ADH) activity, the reversibility of butanol oxidation was studied in vivo and in liver-perfusion systems. Mixtures of [1,1-2H2]ethanol and butanol were given intraperitoneally to deermice lacking (ADH-) or possessing (ADH+) ADH activity, followed by analysis of alcohols in blood by GC/MS. 2H exchange between the two alcohols was seen in all experiments. In ADH- deermice, the 2H excess of butanol increased steadily and reached 18 +/- 5% after 2.5 h. In ADH+ deermice, butanol was rapidly eliminated and the 2H excess was about 7% after 0.5 h. In similar experiments with rats, the 2H excess was about 40% for 2 h. Perfusions of livers from ADH- deermice with mixtures of unlabelled and 1-[2H]butanol showed significant but slow intermolecular hydrogen transfer at C1, indicating oxidoreduction catalyzed by a dehydrogenase. Slow reduction of butanal was observed in mitochondria from ADH- deermice. ADH activity with a pH optimum of 10 and Km for ethanol of 6 mM was detected in the inner mitochondrial membranes from rats and deermice. However, low rates of oxidation observed in experiments carried out with perfused livers and in vitro suggest that this enzyme system does not contribute significantly to alcohol oxidation in vivo. Thus, perfused liver from ADH- deermice appears to be a useful system for studies of ADH-independent oxidation of alcohols. The 2H exchange between the alcohols seen in vivo indicates that both ethanol and butanol are substrates for a common extrahepatic dehydrogenase in ADH- deermice.