Robotic system for cervical spine surgery.

BACKGROUND: In contemporary surgical clinical practice, spinal instability is often treated with mechanical stabilization techniques in order to protect the spinal cord and nerve roots. These techniques involve placing screws in defined regions of the vertebrae, typically the pedicle, where the strongest bone is found. The challenge for the surgeon is the accurate placement of screws for good mechanical purchase and to avoid damage to surrounding vital anatomical structures. This is especially critical in the cervical region, where the target bone mass is smaller and the spinal cord, nerve roots and vertebral arteries are all at risk. A robotic system enabling the surgeon to precisely place implants into the vertebrae should enhance safety and may potentially improve surgical results. METHODS: We describe such a system, which consists of a compact robot positioned using a passive structure, an optical tracking system, a surgical input device and planning and navigational software. The implant trajectory in each vertebra is planned preoperatively, using fine-cut computerized tomography (CT) scans. During surgery, registration matching between the CT scan and the patient's anatomy is achieved using point to point registration, refined with a surface merge technique. Approximate robot positioning is done passively by the surgeon. Final precise instrument positioning is performed by the robot according to the planned trajectory through the target vertebra. Implants (screws) are then placed through the robot-guided working channel. RESULTS: Six cadaver experiments, consisting of placing transarticular (i.e. crossing the joints between the vertebrae) screws in the upper two vertebrae of the human cervical spine, were performed. Implant placement accuracy was comparable with that achieved using freehand image-guided techniques by an experienced surgeon. CONCLUSIONS: These results confirm the utility and applicability of the system. It is currently in redesign to improve accuracy and to render it compatible with on-line planning.

Side-to-side differences in bone strength in master jumpers and sprinters.

INTRODUCTION: This study evaluated side-to-side difference in tibial bone structure, calf muscle cross-sectional area (CSA) and hopping force in master athletes as a result of training for sports with different magnitudes of inter-leg loading difference. METHODS: Tibial bone parameters (at 4%, 14%, 38% and 66% tibial length proximal to distal end), muscle CSA (at 66% tibial length) and hopping forces of both legs of 51 master athletes (conditioned jumpers, conditioned triple jumpers, unconditioned jumpers, hurdlers and sprinters) were examined using pQCT. In epiphyseal 4% slice bone CSA (Ar.tot), total BMC (vBMC.tot), trabecular BMC (vBMC.tb) cortical BMC (vBMC.ct), and trabecular BMD (vBMD.tb) were measured. In diaphyseal slices, Ar.tot, vBMC.ct, cortical density (vBMD.ct), cross-sectional moment of inertia (CSMI) and calf muscle CSA (MuscA) were examined. RESULTS: In conditioned jumpers, side-to-side differences in favour of take-off leg were found in 4% slice in vBMC.tb (+4.1%) (P<0.05). A side-to-side difference was found in 66% slice vBMC.ct and CSMI (both P<0.05), with conditioned jumper (+2.8% and 6.6%) and triple jumper (+2.7% and 7.2%) values higher than other groups. CONCLUSION: The results suggest that regular training in high-impact sports with uneven lower limb loading results in side-to-side differences in skeletal adaptation independent of age and gender, suggesting that high-impact exercise is effective in maintaining bone strength throughout human lifespan.

[The clinical spectrum of urea cycle defects in adult patients]. / Das klinische Spektrum von Harnstoffzyklusdefekten im Erwachsenenalter.

Urea cycle defects belong to the most common metabolic disorders with a cumulative incidence of 1:8000. A common trait of urea cycle defects is a disturbed detoxification of ammonia leading to hyperammonemia in the event of a high nitrogen load. Most patients develop symptoms in the neonatal period or in infancy, e. g. vomiting, seizures and disturbed consciousness. Depending on the affected enzyme and its residual activity, patients differ in the age at first presentation, the character and severity of symptoms and in the susceptibility to metabolic derangement. The presence of hyperammonemia and an altered plasma amino acid profile give the essential diagnostic clues. Since modern therapeutic measures have prolonged the life expectancy of these patients and provided the possibility of a first presentation in adulthood, patients with urea cycle defects have become an increasing challenge in internal medicine. The reported case series illustrates the heterogeneous clinical course of these disorders from childhood to adulthood.

A navigation system for open liver surgery: design, workflow and first clinical applications.

BACKGROUND: The surgical treatment of liver tumours relies on precise localization of the lesions and detailed knowledge of the patient-specific vascular and biliary anatomy. Detailed three-dimensional (3D) anatomical information facilitates complete tumour removal while preserving a sufficient amount of functional liver tissue. METHODS: We present an easy to use, clinically applicable navigation system for efficient visualization and tool guidance during liver surgery. Accurate instrument guidance within 3D planning models was achieved with a fast registration procedure, assuming a locally rigid and temporarily static scenario. After deformations occurring during the procedure, efficient means for registration updates are provided. Special focus was given to workflow integration and the minimization of overhead time. The navigation system was validated with nine clinical cases. RESULTS: Navigated surgical interventions were performed with a median time overhead of 16.5 min. The navigation technology had a median accuracy of 6.3 mm, improving anatomical orientation and the detection of structures at risk. CONCLUSIONS: Successful application of the navigation technology to open liver surgery was achieved by minimizing the procedural complexity and optimizing integration within the existing surgical environment. The assumption of locally rigid patient registration was validated, and clinical evaluation shows clear benefits for the surgeon.

A non-contact mouse for surgeon-computer interaction.

We have developed a system that uses computer vision to replace standard computer mouse functions with hand gestures. The system is designed to enable non-contact human-computer interaction (HCI), so that surgeons will be able to make more effective use of computers during surgery. In this paper, we begin by discussing the need for non-contact computer interfaces in the operating room. We then describe the design of our non-contact mouse system, focusing on the techniques used for hand detection, tracking, and gesture recognition. Finally, we present preliminary results from testing and planned future work.

A haptic guidance tool for CT-directed percutaneous interventions.

We have developed a new navigation approach for computer-assisted interventional radiology. Our system combines a virtual reality display with high-fidelity haptic rendering to provide assistance and guidance of the medical gesture. Specifically, the system is designed to improve the accuracy of blind needle placement within tissues. The proposed technique actively helps the surgeon while keeping him in control of the procedure. We have recently developed an experimental setup for CT-guided biopsy. The setup features a high-precision haptic device connected to the biopsy needle, combined with a graphical interface. The haptic system guides the surgeon's hand to the target tissue based on CT data, whereas a real-time, graphical visualization of the tool trajectory provides navigation information. The setup requires rigid registration of the patient with respect to the haptic interface. Tests have been performed in the presence of radiologists to validate the proposed concept, and early results show that the system is easy to use and requires little training. We are planning to conduct clinical testing in the near future to quantitatively assess system performance.

Multicentre evaluation of in vitro contracture testing with bolus administration of 4-chloro-m-cresol for diagnosis of malignant hyperthermia susceptibility.

BACKGROUND AND OBJECTIVE: The in vitro contracture test with halothane and caffeine is the gold standard for the diagnosis of susceptibility to malignant hyperthermia (MH). However, the sensitivity of the in vitro contracture test is between 97 and 99% and its specificity is 78-94% with the consequence that false-negative as well as false-positive test results are possible. 4-Chloro-m-cresol is potentially a more specific test drug for the in vitro contracture test than halothane or caffeine. This multicentre study was designed to investigate whether an in vitro contracture test with bolus administration of 4-chloro-m-cresol can improve the accuracy of the diagnosis of susceptibility to MH. METHODS: Three hundred and fifty-two patients from 11 European MH laboratories participated in the study. The patients were first classified as MH susceptible, MH normal or MH equivocal by the in vitro contracture test according to the European MH protocol. Muscle specimens surplus to diagnostic requirements were used in this study (MH susceptible = 103 viable samples; MH equivocal = 51; MH normal = 204). 4-Chloro-m-cresol was added to achieve a concentration of 75 micromol L(-1) in the tissue bath. The in vitro effects on contracture development and muscle twitch were observed for 60 min. RESULTS: After bolus administration of 4-chloro-m-cresol, 75 micromol L(-1), 99 of 103 MH-susceptible specimens developed marked muscle contractures. In contrast, only two of 204 MH-normal specimens showed an insignificant contracture development following 4-chloro-m-cresol. From these results, a sensitivity rate of 96.1% and a specificity rate of 99.0% can be calculated for the in vitro contracture test with bolus administration of 4-chloro-m-cresol 75 micromol L(-1). Forty-three patients were diagnosed as MH equivocal, but only specimens from 16 patients developed contractures in response to 4-chloro-m-cresol, indicating susceptibility to MH. CONCLUSIONS: The in vitro contracture test with halothane and caffeine is well standardized in the European and North American test protocols. However, this conventional test method is associated with the risk of false test results. Therefore, an improvement in the diagnosis of MH is needed. Regarding the results from this multicentre study, the use of 4-chloro-m-cresol could increase the reliability of in vitro contracture testing.

HSP70 expression in skeletal muscle of patients with peripheral arterial occlusive disease.

OBJECTIVES: heat shock protein (HSP70) has been studied in the ischaemic myocardium and proven to provide protection against ischaemia. However, HSP70 in ischaemic skeletal muscle in patients with peripheral arterial occlusive disease (PAOD) has not been reported. METHODS: thirty-four patients with PAOD (Fontaine's criteria: stage II: 15; III: 9 and IV: 10, respectively) and ten non-PAOD controls were enrolled in the study. Calf muscle samples were taken. HSP70 was quantitated by SDS-PAGE using ultrasensitive silver staining with reference to a series of standard HSP70, and HSP70 mRNA was estimated using RT-PCR. RESULTS: in comparison with the controls [median with range: 24.8 (14.1-35.6) ng in 2.5 microg total protein], HSP70 was increased significantly in PAOD [stage II: 93.1 (62.7-114.3); stage III: 110.1 (89.7-134.5) and stage IV: 77.4 (67.3-101.1)]. Similar results were obtained with HSP70 mRNA. CONCLUSIONS: HSP70 is increased in the ischaemic skeletal muscle in patients with PAOD, and HSP70 expression is different with regard to clinical stages, and the upregulation of HSP70 mRNA implies that the expression of HSP70 seems to be regulated at transcriptional level.

Distribution and unspecific protein binding of the xenoestrogens bisphenol A and daidzein.

Physiological toxicokinetic (PT) models are used to simulate tissue burdens by chemicals in animals and humans. A prerequisite for a PT model is the knowledge of the chemical's distribution among tissues. This depends on the blood flow and also on the free fraction of the substance and its tissue:blood partition coefficients. In the present study we determined partition coefficients in human tissues at 37 degrees C for the two selected xenoestrogens bisphenol A (BA) and daidzein (DA), and their unspecific binding to human serum proteins. Partition coefficients were obtained by incubating blood containing BA or DA with each of the following tissues: brain, liver, kidney, muscle, fat, placenta, mammary gland, and adrenal gland. Blood samples were analysed by HPLC. For BA and DA, all partition coefficients in non-adipose tissues were similar (average values: BA 1.4, DA 1.2). However, the lipophilic properties of both compounds diverge distinctly. Fat:blood partition coefficients were 3.3 (BA) and 0.3 (DA). These values indicate that with the exception of fat both compounds are distributed almost equally among tissues. In dialysis experiments, the unspecific binding of BA and DA with human serum proteins was measured by HPLC. For BA, the total concentration of binding sites and the apparent dissociation constant were calculated as 2000 and 100 nmol/ml, respectively. Because of the limited solubility of DA, only the ratio of the bound to the free DA concentration could be determined and was found to be 7.2. These values indicate that at low concentrations only small percentages of about 5% (BA) and 12% (DA) are as unbound free fractions in plasma. Since only the unbound fraction can bind to the estrogen receptor, binding to serum proteins represents a mechanism that limits the biological response in target tissues.

[Anesthesia in neuromuscular disorders. Part 2: specific disorders]. / Anästhesie bei neuromuskulären Erkrankungen Teil 2: Spezielle Krankheitsbilder.

The neuromuscular disorders described are divided into four groups: motoneuron diseases, peripheral neuropathies, disturbances of neuromuscular transmission and myopathies. In motoneuron diseases problems mainly result from respiratory insufficiency and the predisposition for aspiration caused by progressive muscular weakness. Depolarising muscle relaxants may elicit myotonic reaction and massive hyperkalemia. In contrast to non-depolarising muscle relaxants there may be an extreme hypersensitivity. In peripheral neuropathies the cardiac function is often limited whereby dysautonomia may enhance cardiovascular instability. The negative inotropic effect of anaesthetic agents must be observed with care and patients with higher degree of AV blocks may need a cardiac pacemaker during general anaesthesia. The Charcot-Marie-Tooth-Syndrome is characterized with a high sensitivity to thiopental. Disturbances of neuromuscular transmission frequently cause respiratory problems The fluctuating weakness of bulbar and respiratory muscles may impair swallowing and can lead to recurrent aspirations. Due to the reduced number of acetylcholine receptors the sensitivity to non-depolarizing muscle relaxants is elevated and the response to succinylcholine is reduced. Drugs reducing neuromuscular transmission such as antibiotics and beta-blockers may enhance these symptoms and should be avoided. In progressive muscular dystrophies the anaesthetic risk is mainly dependent on cardiac and respiratory impairment. Administration of succinylcholine leads to the risk of hyperkalmic cardiac arrest. Patients with metabolic myopathies are also at risk due to the involvement of cardiac muscle but respiratory problems are less frequent. Muscle metabolism should be supported by administration of substrates depending on the underlying disorder. In membrane disorders muscle rigidity (myotonic reactions) or weakness may lead to respiratory insufficiency. In addition to the depolarising muscle relaxants also anticholinesterase drugs, hypothermia and dyskalaemia can evoke myotonic reactions.

[Anesthesia in neuromuscular disorders. Part 1: introduction]. / Anästhesie bei neuromuskulären Erkrankungen. Teil 1: Einführung.

Disorders of skeletal muscle and peripheral nervous system are collectively called neuromuscular disorders (NMD). Important for anesthesia is that these disorders show various symptoms and have a high risk during general anesthesia. Especially administration of succinylcholine and volatile anaesthetics may cause problems. Under special circumstances opioids, nondepolarising muscle relaxants and intravenous anaesthetics can interfere with this kind of disorder, too. Complications during and after anaesthesia may result in malignant hyperthermia, malignant hyperthermia-like reactions and primary or secondary changes relating to the underlying NMD. These include cardiac and respiratory problems, dysautonomia as well as hypothermia or hyperthermia. Thus the perioperative management must be determined individually to assure the best possible safety for each patient. Preoperative examination such as ECG, echocardiography, respiratory function test including arterial blood-gas analysis, x-ray of the thorax, neurological status, and extended serum chemistry (such as CK and myoglobin) needs to be done. For premedication no drugs suppressing respiratory function should be administered. Regional anesthesia should be used whenever possible, especially in patients with respiratory and cardiac problems. The dosage of all recommended drugs should be as low as possible. Volatile anaesthetics should not be administered in the majority of NMD and succinylcholine is contraindicated, with the exception of myasthenia gravis. Additionally to the usual intraoperative monitoring, the invasive measurement of blood pressure allows frequent blood-gas analysis. It is obligate to monitor neuromuscular function and body temperature. During recovery special attention should be paid to maintain normal body temperature and electrolytes and acid-base status. The discharge of the patient from the recovery area to the normal ward should be performed only after respiratory function is normalized.

Kinetics of propylene oxide metabolism in microsomes and cytosol of different organs from mouse, rat, and humans.

Kinetics of the metabolic inactivation of 1,2-epoxypropane (propylene oxide; PO) catalyzed by glutathione S-transferase (GST) and by epoxide hydrolase (EH) were investigated at 37 degrees C in cytosol and microsomes of liver and lung of B6C3F1 mice, F344 rats, and humans and of respiratory and olfactory nasal mucosa of F344 rats. In all of these tissues, GST and EH activities were detected. GST activity for PO was found in cytosolic fractions exclusively. EH activity for PO could be determined only in microsomes, with the exception of human livers where some cytosolic activity also occurred, representing 1-3% of the corresponding GST activity. For GST, the ratio of the maximum metabolic rate (V(max)) to the apparent Michaelis constant (K(m)) could be quantified for all tissues. In liver and lung, these ratios ranged from 12 (human liver) to 106 microl/min/mg protein (mouse lung). Corresponding values for EH ranged from 4.4 (mouse liver) to 46 (human lung). The lowest V(max) value for EH was found in mouse lung (7.1 nmol/min/mg protein); the highest was found in human liver (80 nmol/min/mg protein). K(m) values for EH-mediated PO hydrolysis in liver and lung ranged from 0.83 (human lung) to 3.7 mmol/L (mouse liver). With respect to liver and lung, the highest V(max)/K(m) ratios were obtained for GST in mouse and for EH in human tissues. GST activities were higher in lung than in liver of mouse and human and were alike in both rat tissues. Species-specific EH activities in lung were similar to those in liver. In rat nasal mucosa, GST and EH activities were much higher than in rat liver.

Toxicokinetics of inhaled propylene in mouse, rat, and human.

A physiological toxicokinetic (PT) model was developed for inhaled propylene gas (PE) in mouse, rat, and human. Metabolism was simulated to occur in the liver (90%) and in the richly perfused tissue group (10%). The partition coefficients tissue:air were determined in vitro using tissues of mice, rats, and humans. Most of the tissues have partition coefficients of around 0.5. Only adipose tissue displays a 10 times higher value. The partition coefficient blood:air in human is 0.44, about half of that in rodents. PE can accumulate in the organism only barely. For male B6C3F1 mice and male Fischer 344/N rats, parameters of PE metabolism were obtained from gas uptake experiments. Maximum rates of metabolism (V(maxmo)) were 110 micromol/h/kg in mice and 50.4 micromol/h/kg in rats. V(maxmo)/2 was reached in mice at 270 ppm and in rats at 400 ppm of atmospheric PE. Pretreatment of the animals with sodium diethyldithiocarbamate resulted in an almost complete inhibition of PE metabolism in both species. Preliminary toxicokinetic data on PE metabolism in humans were obtained in one volunteer who was exposed up to 4.5 h to constant concentrations of 5 and 25 ppm PE. The PT model was used to calculate PE blood concentrations at steady state. At 25 ppm, the blood values were comparable across species, with 0.19, 0.32, and 0.34 micromol/L for mouse, rat, and human, respectively. However, the corresponding rates of PE metabolism differed dramatically, being 8.3, 2.1, and 0.29 micromol/h/kg in mouse, rat, and human. For a repeated human exposure to 25 ppm PE in air (8 h/day, 5 days/week), PE concentrations in venous blood were simulated. The prediction demonstrates that PE is eliminated so rapidly that it cannot accumulate in the organism. For low exposure concentrations, it became obvious that the rate of uptake into blood by inhalation is limited by the blood flow through the lung and the rate of metabolism is limited by the blood flow through the metabolizing organs.

Xenon does not induce contracture in human malignant hyperthermia muscle.

Xenon has many characteristics of an ideal anaesthetic agent. It is not known whether xenon is a safe alternative to the potent inhalational anaesthetics in patients susceptible to malignant hyperthermia (MH). We investigated the effect of xenon, halothane and caffeine on muscle specimens of 31 individuals, referred to the MH Unit of the University of Ulm, and performed genetic epidemiology. Thirteen individuals were classified as MH susceptible and 18 as MH negative. Xenon 70% did not cause an increase in baseline tension of any MH-susceptible muscle specimen in contrast to halothane and caffeine. The evoked twitch response increased transiently in MH-susceptible and normal specimens indicating a mechanism independent of MH susceptibility. These results suggest that xenon, in concentrations up to 70% may be a safe anaesthetic for MH-susceptible patients.

Human skeletal muscle HSP70 response to physical training depends on exercise intensity.

We have previously reported that HSP70 in human skeletal muscle could be induced by training. However, whether HSP70 induction is dependent upon exercise volume or exercise intensity remains unknown. The aim of the present study was to investigate the relationship between HSP70 and training intensity in rowers. Fourteen well-trained male rowers were divided into two groups (group A, n = 6; group B, n = 8). Group A performed higher intensity exercise during 1st phase, whereas group B performed higher intensity exercise during 2nd training phase. Training volume in 2nd phase increased in both groups. Both training intensity and volume were reduced in 3rd phase. Muscle samples were taken from m. vastus lateralis by fine needle biopsy before training, at the end of the 1st, 2nd and 3rd training phases. HSP70 was quantitatively determined using SDS-PAGE with silver stain. In group A, HSP70 increased significantly from 38 +/- 12 etag before training to 59 +/- 16 etag at the end of the lst training phase (loaded total protein 2.5microg), and decreased afterwards. In group B, HSP70 increase (from 36 +/- 11 etag to 50 +/- 13 etag) in the 1st phase was significantly smaller, there was a further increase of HSP70 in the 2nd phase (60 +/- 14 etag). At the end of the training, HSP70 decreased in both groups. Thus, HSP70 response to training seems to be dependent upon exercise intensity.

Limiting factors on the transformative powers of e-mail in patient-physician relationships: a critical analysis.

In this article I analyze doctor-patient use of e-mail within the context of the evolving doctor-patient relationship and ongoing changes in the U.S. health care system. Evidence from the published literature on doctor-patient relationships and doctor-patient communication, empirical studies of uses of the Internet by doctors and patients, and commentaries about the Internet's role in health care are examined and discussed to reveal common, unsupported assumptions about the likely impact of e-mail on the doctor-patient relationship and also the value structure associated with current e-mail practices between doctors and patients. I argue that existing research does not adequately account for the technical, professional, and economic forces that are shaping doctor-patient use of e-mail. I conclude that physicians' preferences for technical, instrumental exchanges with patients will likely mitigate the positive influence that e-mail could have on the doctor-patient relationship, and doctor-patient communication is unlikely to improve as a result of their use of e-mail.

[Clonidine compared to midazolam for intravenous premedication for ambulatory procedures. A controlled double blind study in ASA 1 patients]. / Clonidin im Vergleich zu Midazolam zur intravenösen Prämedikation vor ambulanten Eingriffen. Eine kontrollierte Doppelblindstudie bei ASA 1-Patienten.

OBJECTIVE: Midazolam is frequently used for premedication in day-case surgical patients whereas clonidine is rarely administered for this indication. However, clonidine has several useful effects that make the drug an interesting alternative to conventional premedicants. Thus, in this randomised, double-blind, and controlled study the anxiolytic effect of midazolam was compared to that of clonidine. Furthermore, effects on postoperative complaints and minor complications, and readiness for discharge were investigated. METHODS: 100 ASA-1 patients undergoing wisdom teeth extraction on a day-case basis were included into the analysis. A further 50 patients who received no premedication served as a control group. General anaesthesia was standardised (propofol-fentanyl-isoflurane in N2O/O2). The anxiolytic effect of the premedication was assessed using the Erlanger anxiety- and tension scale (EAS). The test was applied before and after intravenous premedication with 1.5 micrograms/kg clonidine or 50 micrograms/kg midazolam and repeated once postoperatively. During recovery the incidence and severity of pain, nausea and vomiting, and shivering were recorded. The readiness for discharge was assessed using standardised discharge criteria. The recording of data was completed by a telephone interview on the day after surgery. RESULTS: The demographic data of the groups did not differ. In the two treatment groups there was a time-dependent decrease of anxiety and tension. However, postoperatively there was no difference between the levels of anxiety and inner tension between the premedicated patients and the untreated control group. Furthermore there was no difference in the incidence and severity of any postoperative complications. Time until the patients were ready for discharge did not differ between the three groups. CONCLUSION: The effects of an intravenous premedication with 1.5 micrograms/kg clonidine or 50 micrograms/kg midazolam, respectively in young ASA-1 patients undergoing minor surgical procedures on a day-case basis are restricted to decrease of anxiety and inner tension before surgery. No beneficial effects were found during the postoperative period compared with untreated control patients.

A physiological toxicokinetic model for exogenous and endogenous ethylene and ethylene oxide in rat, mouse, and human: formation of 2-hydroxyethyl adducts with hemoglobin and DNA.

Ethylene (ET) is a gaseous olefin of considerable industrial importance. It is also ubiquitous in the environment and is produced in plants, mammals, and humans. Uptake of exogenous ET occurs via inhalation. ET is biotransformed to ethylene oxide (EO), which is also an important volatile industrial chemical. This epoxide forms hydroxyethyl adducts with macromolecules such as hemoglobin and DNA and is mutagenic in vivo and in vitro and carcinogenic in experimental animals. It is metabolically eliminated by epoxide hydrolase and glutathione S-transferase and a small fraction is exhaled unchanged. To estimate the body burden of EO in rodents and human resulting from exposures to EO and ET, we developed a physiological toxicokinetic model. It describes uptake of ET and EO following inhalation and intraperitoneal administration, endogenous production of ET, enzyme-mediated oxidation of ET to EO, bioavailability of EO, EO metabolism, and formation of 2-hydroxyethyl adducts of hemoglobin and DNA. The model includes compartments representing arterial, venous, and pulmonary blood, liver, muscle, fat, and richly perfused tissues. Partition coefficients and metabolic parameters were derived from experimental data or published values. Model simulations were compared with a series of data collected in rodents or humans. The model describes well the uptake, elimination, and endogenous production of ET in all three species. Simulations of EO concentrations in blood and exhaled air of rodents and humans exposed to EO or ET were in good agreement with measured data. Using published rate constants for the formation of 2-hydroxyethyl adducts with hemoglobin and DNA, adduct levels were predicted and compared with values reported. In humans, predicted hemoglobin adducts resulting from exposure to EO or ET are in agreement with measured values. In rodents, simulated and measured DNA adduct levels agreed generally well, but hemoglobin adducts were underpredicted by a factor of 2 to 3. Obviously, there are inconsistencies between measured DNA and hemoglobin adduct levels.