Absence of PO2 change in fetal brain despite PO2 increase in placenta in response to maternal oxygen challenge.

OBJECTIVE: Magnetic resonance imaging allows the noninvasive observation of PO2 changes between air breathing and oxygen breathing through quantification of the magnetic longitudinal relaxation time T1. Changes in PO2 are proportional to changes in the longitudinal relaxation rate ΔR1 (where ΔR1=1/T1oxygen-1/T1air). Knowledge of this response could inform clinical interventions using maternal oxygen administration antenatally to treat fetal growth restriction. We present in vivo measurements of the response of the fetal-placental unit to maternal hyperoxia. DESIGN: Prospective cohort. SETTING: Large tertiary maternity hospital. SAMPLE: Nine women undergoing low-risk pregnancy (21-33 weeks of gestation) and five nonpregnant adults. METHODS: During imaging the air supply to mothers was changed from medical air (21% oxygen) to medical oxygen (100% oxygen) and T1 was monitored over time in both the placenta and fetal brain using a periodically repeated magnetic resonance imaging sequence. To demonstrate that the method could detect a brain response, brain responses from five normal adult volunteers were measured using a similar imaging protocol. MAIN OUTCOME MEASURE: Changes in T1 following oxygen challenge. RESULTS: No significant ΔR1 (P=0.42, paired t-test) was observed in fetal brains. A significant placental ΔR1 (P=0.0002, paired t-test) of 0.02±0.01/s (mean±SD) was simultaneously observed in the same participants. In the brains of the nonpregnant adults, a significant ΔR1 (P=0.01, paired t-test) of 0.005±0.002/s was observed. CONCLUSION: Short-term maternal oxygen administration does not improve fetal brain oxygenation, in contrast to the response observed in the adult brain.

Constraint-induced movement therapy: characterizing the intervention protocol.

Constraint-induced movement therapy (CI therapy) is a rehabilitation treatment approach that improves more-affected extremity use following a stroke, especially in the life situation. The originators of the approach describe CI therapy as consisting of a family of therapies including a number of treatment components and subcomponents. When thinking of CI therapy, rehabilitation researchers and clinicians frequently cite a restraining mitt on the less affected arm as the main active ingredient behind improvements in motor function. However, substantial data suggest that restraint makes actually a relatively small contribution to treatment outcome. This paper provides a detailed description of the multiple treatment elements included in the CI therapy protocol as used in our research laboratory. Our aim is to improve understanding of CI therapy and the research supporting its use.

Neuroplasticity and constraint-induced movement therapy.

Recent years have seen a proliferation of animal and human studies that have associated significant changes in regional brain physiology with sustained altered environmental or somatic stimuli. The behavioral consequences in such instances can be adaptive or maladaptive. As would be expected, constraint-induced movement therapy (CI therapy), which has been found to be beneficial for chronic stroke hemiparesis, has been repeatedly associated with significant plastic brain changes in a variety of studies that have included transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), or other approaches. In some instances, the initial degree of brain reorganization occurred in parallel with the improvement in spontaneous, real-world use by the more-affected hand, which suggests that plastic brain changes in some manner support therapeutic effects. However, the studies are also inconsistent with respect to whether the reorganization changes occur more in the lesioned vs unlesioned hemisphere. Interpreting the physiological outcomes post-treatment is compromised by inconsistencies in study design in the nature of treatment administered, participant recruitment, imaging modality, and extent of follow-up. Improved understanding of the biological basis for neuroplasticity in CI therapy may be obtained through rigorous control of study approaches and through evaluating treatment changes with more than one modality in the same patients concurrently. New quantitative structural brain imaging techniques may allow measuring morphological changes following CI therapy to test hypotheses of regional brain recruitment in use-dependent therapy while avoiding the variability of functional imaging and mapping techniques and the difficulties and assumptions imposed by requiring active limb movement during scanning.

The learned nonuse phenomenon: implications for rehabilitation.

Research on monkeys with a single forelimb from which sensation is surgically abolished demonstrates that such animals do not use their deafferented limb even though they possess sufficient motor innervation to do so, a phenomenon labeled learned nonuse. This dissociation also occurs after neurological injury in humans. Instruments that measure these two aspects of motor function are discussed. The effects of a neurological injury may differ widely in regard to motor ability assessed on a laboratory performance test in which movements are requested and actual spontaneous use of an extremity in real-world settings, indicating that these parameters need to be evaluated separately. The methods used in Constraint-Induced Movement therapy (CI therapy) research to independently assess these two domains are reliable and valid. We suggest that these tests have applicability beyond studies involving CI therapy for stroke and may be of value for determining motor status in other types of motor disorders and with other types of treatment. The learned nonuse formulation also predicts that a rehabilitation treatment may have differential effects on motor performance made on request and actual spontaneous amount of use of a more affected upper extremity in the life situation. CI therapy produces improvements in the former, but focuses attention on the latter and, in fact, spontaneous use of the limb is where this intervention has by far its greatest effect. The evidence suggests that this result is driven by use of a ''transfer package'' of techniques, which can be used with other therapies to increase the transfer of improvements made in the clinic to the life situation. The use of CI therapy in humans began with the upper extremity after stroke and was then extended for the upper extremity to cerebral palsy in young children (8 months to 8 years old) and traumatic brain injury. A form of CI therapy was developed for the lower extremities and was used effectively after stroke, spinal cord injury, and fractured hip. Adaptations of CI therapy have also been developed for aphasia (CI aphasia therapy), focal hand dystonia in musicians and phantom limb pain. The range of these applications suggests that CI therapy is not only a treatment for stroke, for which it is most commonly used, but for learned nonuse in general, which manifests as excess motor disability in a number of conditions which until now have been refractory to treatment.

Purification, partial characterization, and clinical evaluation of an adenocarcinoma-associated antigen.

The current investigation describes the purification and partial characterization of a new adenocarcinoma-associated antigen (ACAA). ACAA is a large molecular weight glycoprotein (Mr 790,000 by size chromatography on Sepharose CL-6B) that migrates in the alpha 1 region upon electrophoresis and is eluted from a DEAE-cellulose column at a 0.1 M NaCl concentration. ACAA is immunochemically and biochemically different from carcinoembryonic antigen, alpha-fetoprotein, pancreatic oncofetal antigen, human pancreatic tissue antigen, CA 19-9, ferritin, and acute-phase proteins. Assays for ACAA were carried out using a solid-phase sandwich enzyme immunoassay. The results indicate that ACAA is present in sera of all individuals. Patients with cancer have higher serum levels of ACAA than normal individuals. The greatest frequency of elevated serum values of ACAA was seen in patients with lung and pancreatic cancers followed by colorectal, breast, and prostate cancer. The measurement of ACAA levels may be valuable in the diagnosis and clinical management of patients with certain cancers.

Development of a diffusion-weighted MRI protocol for multicentre abdominal imaging and evaluation of the effects of fasting on measurement of apparent diffusion coefficients (ADCs) in healthy liver.

OBJECTIVE: To assess the effect of fasting and eating on estimates of apparent diffusion coefficient (ADC) in the livers of healthy volunteers using a diffusion-weighted MRI protocol with b-values of 100, 500 and 900 s mm(-2) in a multicentre study at 1.5 T. METHODS: 20 volunteers were scanned using 4 clinical 1.5-T MR scanners. Volunteers were scanned after fasting for at least 4 h and after eating a meal; the scans were repeated on a subsequent day. Median ADC estimates were calculated from all pixels in three slices near the centre of the liver. Analysis of variance (ANOVA) was used to assess the difference between ADC estimates in fasted and non-fasted states and between ADC estimates on different days. RESULTS: ANOVA showed no difference between ADC estimates in fasted and non-fasted states (p = 0.8) nor between ADC estimates on different days (p = 0.8). The repeatability of the measurements was good, with coefficients of variation of 5.1% and 4.6% in fasted and non-fasted states, respectively. CONCLUSION: There was no significant difference in ADC estimates between fasted and non-fasted measurements, indicating that the perfusion sensitivity of ADC estimates obtained from b-values of 100, 500 and 900 s mm(-2) is sufficiently low that changes in blood flow in the liver after eating are undetectable beyond the variability in the measurements. ADVANCES IN KNOWLEDGE: Assessment of the effect of prandial state on ADC estimates is critical, in order to determine the appropriate patient preparation for biological validation in clinical trials.

Inhibition of peripheral aromatization in the male cynomolgus monkey by a novel nonsteroidal aromatase inhibitor (R 76713).

R 76713 (6-[(4-chlorophenyl)(1-H-1,2,4-trizol-1-yl)methyl]1-H benzotriazole) is a highly potent and selective inhibitor of the aromatase enzyme both in vitro and in vivo. The ability of R 76713 to inhibit peripheral aromatization of androstenedione (A) to estrone (E1) in vivo was studied in male cynomolgus monkeys (Macaca fascicularis). Peripheral aromatization was measured using a primed constant infusion of [3H] A and [14C]E1 for 3.5 h. Blood samples, collected during the final hour of infusion, were analyzed for plasma radioactivity as infused and product steroids. MCRs, conversion ratios (CR), and percent conversion of A to E1 were calculated. R 76713 (0.03-10 microgram/kg) or vehicle (10% hydroxypropyl-beta-cyclodextrin) were administered iv 90 min before beginning the infusion of radiolabeled steroids. In vehicle-treated monkeys, the aromatization of A (mean +/- SEM, 1.35 +/- 0.11%) was similar to that previously reported for cynomolgus and rhesus monkeys, baboons, and humans. Aromatization of A, measured 4-5 h after injection of R 76713, was dose-dependently decreased from the control value by 87 +/- 3%, 85 +/- 2%, 61 +/- 5%, and 33 +/- 8% (all P less than 0.05) at doses of 10.0, 3.0, 0.3, and 0.03 micrograms/kg, respectively, with an ID50 of 0.13 microgram/kg, iv (95% confidence interval, 0.06-0.21). When measured 15-16 h after iv administration of 3.0 micrograms/kg R 76713, aromatization (0.55 +/- 0.13%) was significantly inhibited by 53 +/- 11% compared to that in control monkeys (1.16 +/- 0.18%). The CRs between androgens, the CRs between estrogens, and the MCRs of A and E1 were not significantly altered by R 76713 compared to those after vehicle treatment. R 76713 potently decreased peripheral conversion of androgen to estrogen in vivo in male cynomolgus monkeys and may be a useful therapeutic agent in treating estrogen-dependent diseases, including post-menopausal breast cancer.

Prospective CYP2D6 genotyping as an exclusion criterion for enrollment of a phase III clinical trial.

A phase III study was performed to compare the efficacy and safety of lamotrigine (Lamictal), desipramine (Norpramin), and placebo in the treatment of unipolar depression. Desipramine is extensively metabolized by cytochrome P450 2D6 (CYP2D6), and kinetics of this compound are altered in poor metabolizers. Genotyping was utilized to exclude poor metabolizers in order to increase subject safety and to eliminate the need to continuously monitor plasma desipramine levels. As part of screening, subjects were genotyped for the *3(A), *4(B), and *5(D) alleles, which identify approximately 95% of poor metabolizers. Extensive metabolizers were eligible for randomization to the lamotrigine, desipramine, or placebo arm. Follow-up genotyping for the *6(T) and *7(E) alleles was performed after study enrollment and was used to identify poor metabolizers who may have been incorrectly identified as extensive metabolizers upon initial three-allele screening. Of 628 subjects screened for *3(A), *4(B), *5(D) alleles, 590 (93.9%) were classified as extensive metabolizers. The remaining 38 (6.1%) subjects were poor metabolizers and excluded. Subsequent *6(T) and *7(E) testing revealed that two poor metabolizers had been enrolled, and the follow-up genotyping provided an explanation for the high desipramine plasma concentrations in one subject. No differences in phenotypic or allelic frequencies were found between the study population and literature populations. However, the frequency of poor metabolizers varied among clinical sites (0-15%). For a compound that is extensively metabolized by CYP2D6, prescreening subjects for *3(A), *4(B), *5(D), *6(T) and *7(E) alleles can increase subject safety and eliminate the need to continuously monitor drug plasma concentrations.

Infection among 210 patients with surgically staged Hodgkin's disease.

To determine the incidence and types of infections in Hodgkin's disease, particularly those related to the overwhelming pneumococcal sepsis syndrome, 210 consecutive patients with previously untreated Hodgkin's disease who underwent staging laparotomy with splenectomy from March 1968 to October 1979 were reviewed. For 178 patients (85 percent) alive at the end of the study, the mean follow-up time was 68.1 months. Eighty-two serious infections occurred among 59 (28 percent) of the patients; 47 (57 percent) serious infections were microbiologically documented and 35 (43 percent) were clinically documented. Forty-seven microbiologically documented serious infections occurred in 34 patients and consisted of 23 episodes of pneumonia, 10 cases of bacteremia, seven wound infections, two cases of disseminated herpes zoster, one subphrenic abscess, and four miscellaneous infections. Microbiologically documented serious infections occurring during initial treatment or remission had lower incidences of leukopenia (29 versus 58 percent) (p = 0.09) and death (11 versus 53 percent) (p = 0.005) than those occurring after relapse of Hodgkin's disease. Of the microbiologically documented serious infections, 76 percent were associated with a predisposing factor(s) (leukopenia, postoperative state, steroids, peripheral neuropathy, leukemia), of which 34 percent were fatal. Microbiologically documented serious infections unassociated with a predisposing factor were never fatal, including the only episode of pneumococcal sepsis in the series. In contrast to microbiologically documented serious infections, only 14 percent of clinically documented serious infections (versus 38 percent) were fatal. The overwhelming pneumococcal sepsis syndrome and other infections thought to be associated with the asplenic state are uncommon problems in patients with Hodgkin's disease after splenectomy.

Differential effects of heparin on the early and late phases of hepatic ischemia and reperfusion injury in the pig.

The mechanisms by which heparin protects the liver during induced episodes of liver ischemia-reperfusion are poorly understood. Previous work in a swine model demonstrated that serum levels of glycohydrolases and lipid peroxide peaked within 3 h after 45 minutes of hepatic ischemia followed by reperfusion. Serum levels of lactate dehydrogenase and aspartate aminotransferase peaked 20-24 h later. The aim of this study was to evaluate the effect of heparin on these two-phases of enzyme release, using a pig model of hepatic ischemia-reperfusion injury. Twenty male swine were divided into control (n = 8) and heparin (n = 12) groups. In the heparin group, heparin was administered prior to and concurrent with ischemia-reperfusion. Following 45 min of hepatic ischemia, the levels of beta-galactosidase, beta-glucosidase, acid phosphatase, purine nucleoside phosphorylase, lipid peroxides, lactate dehydrogenase, and aspartate aminotransferase in serum were monitored for up to 166 h and compared to pre-ischemic and control levels. With heparin infusion, the peak levels of beta-galactosidase, beta-glucosidase, and the lipid peroxide were reduced to 50-60% of the control levels. Acid phosphatase and purine nucleoside phosphorylase activities in serum were reduced to 25% and 60%, respectively. The peak concentrations of lactate dehydrogenase and aspartate aminotransferase were reduced to about 25% of the control level. In addition, the serum enzymes of control pigs did not return to pre-ischemic levels until 2 weeks after hepatic ischemia, while they normalized in less than 1 week in the heparin-treated animals. Systemic heparinization had different protective effects on the first and secondary phases of liver injury. These differences may reflect heparin protection of different types of liver cells. The protection of the parenchymal cells may be the combined result of reduced sinusoidal cell injury and the anticoagulant properties of heparin.

Serum concentrations of chromium, cobalt and nickel after total hip replacement: a six month study.

Serum specimens were obtained from 15 patients before undergoing conventional total hip replacement and for periods of up to six months postoperatively. The specimens were analysed for chromium, cobalt and nickel by electrothermal atomic absorption spectroscopy. Serum chromium levels were found to rise to a pronounced postoperative peak and then diminish, although not falling to normal mean levels by six months. Serum cobalt levels either remained the same or decreased while serum nickel levels began to rise two to six weeks after surgery. These results are significant in that serum metal concentration changes have been reported for patients receiving metal-on-metal implants but not for patients with metal-on-polymer total hip implants of more modern designs.

Use of carbon fibers for repair of abdominal-wall defects in rats.

Carbon in the form of 8-micron fibers induces growth of connective tissue. The purpose of this study was to measure and histologically characterize tissue ingrowth occurring in carbon fibers implanted for up to 12 months in abdominal-wall defects in rats, compared with polypropylene mesh. Carbon fibers induced significantly more tissue ingrowth than polypropylene mesh at 6 to 12 months postoperatively. The predominant tissues associated with carbon fibers and polypropylene mesh were dense connective tissue and fat, respectively. Fragmentation of the implants did not occur, and implant debris was not found in the regional lymph nodes. Carbon fibers are potentially useful for reinforcing abdominal-wall defects.

Lamivudine/zidovudine as a combined formulation tablet: bioequivalence compared with lamivudine and zidovudine administered concurrently and the effect of food on absorption.

A single-center, open-label, three-way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined lamivudine 150 mg/zidovudine 300 mg tablet relative to the separate brand-name components administered concurrently and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 5- to 7-day washout period: one lamivudine/zidovudine combination tablet after an overnight fast, one lamivudine 150 mg tablet and one zidovudine 300 mg tablet simultaneously after an overnight fast, or one lamivudine/zidovudine combination tablet 5 minutes after completing a standardized high-fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for the determination of lamivudine and zidovudine plasma concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals for the ratio of least squares (LS) means for the lamivudine and zidovudine area under the plasma concentration-time curve (AUC infinity) and maximum observed plasma concentration (Cmax) fell entirely within 0.80 to 1.25 for log-transformed parameters. The combined lamivudine/zidovudine tablet was bioequivalent in the extent (AUC infinity) and rate of absorption (Cmax and time of Cmax [tmax]) to the individual brand-name drug components administered concurrently under fasted conditions. Geometric LS mean ratios and 90% confidence intervals for AUC infinity and Cmax were 0.97 (0.92, 1.03) and 0.94 (0.84, 1.06), respectively, for lamivudine and 0.99 (0.91, 1.07) and 0.97 (0.82, 1.15), respectively, for zidovudine. The extent of absorption of lamivudine and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the tmax, and reduced the Cmax of lamivudine and zidovudine. These changes were not considered clinically important. All formulations were well tolerated under fasted and fed conditions.

Pharmacokinetics, absolute bioavailability, and absorption characteristics of lamivudine.

Lamivudine is a novel cytosine nucleoside analog, reverse transcriptase inhibitor that has shown activity against human immunodeficiency virus (HIV) types 1 and 2 and hepatitis B virus in vitro. This study was conducted to compare the absolute bioavailability, pharmacokinetics, and absorption characteristics of oral solution, 100-mg capsule, and 100-mg tablet formulations of lamivudine with those of intravenous lamivudine. Twelve patients with HIV were enrolled in a single-center, randomized, open-label, four-way cross-over study. Treatment arms consisted of 100 mg intravenous lamivudine (administered over 1 hour), 100 mg oral lamivudine (1 mg/mL), a 100-mg capsule, and a 100-mg tablet, each followed by a 3- to 14-day washout period. Serial blood samples over 24 hours were obtained after each dose administration. Serum concentration data were analyzed to determine pharmacokinetic parameter estimates including area under the curve (AUC), terminal half-life (t1/2), mean residence time (MRT) for each formulation, systemic clearance, oral clearance, and apparent volume of distribution (Vd). Absolute bioavailability and in vivo mean absorption time (MAT) and mean dissolution time (MDT) were calculated for the oral formulations. Deconvolution techniques were used to calculate the input rate for the oral solution, capsule, and tablet. The two one-sided t test was used to determine bioequivalency among oral formulations with respect to logarithmic transformed estimates of AUC and maximum peak concentration (Cmax). Mean (CV) systemic clearance and Vdss after intravenous administration of lamivudine were 22.6 L/h (15%) and 99 L (28%), respectively; mean t1/2 ranged from 8.41 to 9.11 hours for all formulations; and MRT ranged from 4.42 to 5.77 hours for all formulations. Mean absolute bioavailability ranged from 86% to 88% for the oral solution, capsule, and tablet. All oral formulations were considered bioequivalent for AUC and Cmax. The MAT was 1.32 hour for the oral solution, and MDT was 0.03 and -0.11 hours for the capsule and the oral solution, respectively. The oral formulations of lamivudine examined in this study demonstrated acceptable bioavailability for oral administration. The solid oral formulations (capsule and tablet) show rapid dissolution properties with an absorption rate similar to or exceeding those observed with the oral solution. This suggests that dissolution is not an important factor for the rate of absorption of lamivudine. The use of deconvolution techniques using PCDCON provides valuable insight into the absorption characteristics of lamivudine.

The dynamic Morris biphase appliance for stabilization of flail facial bones.

This report presents our experience with a modification of the Morris biphase appliance. We have modified the device to let the patient open his or her mouth immediately after surgery to allow for intraoral suture line care. The device prevents deviation of the remaining mandible toward the operated side of the face. We believe this has lessened the esthetic, masticatory, and speech difficulties of the two patients in whom we used the device. We conclude the device deserves further testing.

Combination chemotherapy for advanced squamous cell carcinoma of the head and neck.

Fifty-one patients (32 previously untreated, 19 previously treated) with advanced squamous cell carcinoma of the head and neck received a single course of combination chemotherapy consisting of high dose cis-platinum (DDP), bleomycin (Bleo), +/- high dose methotrexate (MTX). Thirty-three (65%) patients responded to therapy; 5 (10%) of these patients had a complete response. Previously untreated patients and those who received the three drugs (DDP, Bleo and MTX) had the highest response rates. The duration of response was 8 to 12 weeks. Seven (15%) patients showed a two-year survival rate. All nonresponders were dead of disease within two years. Three (56%) of the five complete-response patients and 4 (21%) of the partial-response patients survived for two years. The role of preoperative chemotherapy in head and neck cancer is yet to be conclusively defined.

Loop colostomies are totally diverting in adults.

Temporary colostomy is a mainstay in the treatment of patients with colon injuries. Common teaching is that loop colostomies are not totally diverting. We performed this study to determine whether loop colostomies are totally diverting. Twenty-three patients presenting for closure of loop colostomies were given barium by mouth. Serial abdominal films were obtained at intervals over 24 hours. Scout films were obtained after bowel preparation to see if flushing the colon could cause passage of barium into distal bowel. We could not demonstrate passage of barium into the distal limb of the colon in any patient studied. This was true even in long-established loop colostomies. Bowel preparation did not cause passage of barium into the distal colon. Loop colostomies constructed over a rod and matured immediately totally divert the fecal stream. Most surgeons would agree that this type of colostomy is more easily and quickly created and closed. Since it fulfills the criteria for fecal diversion, the use of divided colostomies should be abandoned when a loop colostomy can be utilized.

Shotgun wounds involving the head and neck.

Since limited information is available on the management and spectrum of injuries sustained by patients with shotgun wounds to the head and neck, we reviewed the records of 26 patients with shotgun wounds involving the head and neck region. Fifty-four percent of these patients had associated injuries involving the trunk or extremities, and 43 percent of these patients required repair of these associated injuries. Overall, 23 percent of patients with shotgun wounds of the head and neck region had injuries of other anatomic areas that required operative treatment. In these patients, the major life-threatening injuries were not related to the head and neck region but were related to injuries of other anatomic areas. By stratifying the patients according to the anatomic pattern of injury (point blank, close range, or long range) and their hemodynamic status on presentation to the emergency room, it was possible to predict the need for surgery as well as the risk of death.

Nonfunctioning retroperitoneal paragangliomas.

Nonfunctioning paragangliomas of the retroperitoneum are extremely rare tumors. As of this report, 30 cases are known from published data. Characteristics of these tumors and diagnostic techniques are herein described. Approximately 20 percent of these lesions are considered malignant. Surgical resection is the treatment of choice once the diagnosis is made.

Cranial nerve injuries during carotid endarterectomy.

Our experience with patients undergoing carotid endarterectomy over a 10 year period has been retrospectively reviewed. Nerve injuries were detected by reviewing postoperative progress and clinic notes. One hundred twenty-nine procedures were performed on 112 patients, 12 of whom (9.3 percent) sustained major nerve injuries. These included five vagal nerve injuries causing ipsilateral vocal cord paralysis and hoarseness, four injuries of the marginal mandibular nerve, and three injuries of the hypoglossal nerve. Evidence of nerve dysfunction was not present preoperatively. None of the patients with nerve injury sustained a stroke as a result of carotid operation. Vocal cord paralysis was documented by indirect laryngoscopy. The incidence of cranial nerve injury during carotid endarterectomy appears to be higher than expected, particularly if asymptomatic patients are investigated; however, most injuries are transient and result not from transection but from trauma during dissection, retraction, and clamping of the vessels. The pertinent anatomy and techniques for preventing these injuries have been reviewed.