Frontal plane knee alignment mediates the effect of frontal plane rearfoot motion on knee joint load distribution during walking in people with medial knee osteoarthritis.

OBJECTIVE: To examine the nature of differences in the relationship between frontal plane rearfoot kinematics and knee adduction moment (KAM) magnitudes. DESIGN: Cross-sectional study resulting from a combination of overground walking biomechanics data obtained from participants with medial tibiofemoral osteoarthritis at two separate sites. Statistical models were created to examine the relationship between minimum frontal plane rearfoot angle (negative values = eversion) and different measures of the KAM, including examination of confounding, mediation, and effect modification from knee pain, radiographic disease severity, static rearfoot alignment, and frontal plane knee angle. RESULTS: Bivariable relationships between minimum frontal plane rearfoot angle and the KAM showed consistent negative correlations (r = -0.411 to -0.447), indicating higher KAM magnitudes associated with the rearfoot in a more everted position during stance. However, the nature of this relationship appears to be mainly influenced by frontal plane knee kinematics. Specifically, frontal plane knee angle during gait was found to completely mediate the relationship between minimum frontal plane rearfoot angle and the KAM, and was also an effect modifier in this relationship. No other variable significantly altered the relationship. CONCLUSIONS: While there does appear to be a moderate relationship between frontal plane rearfoot angle and the KAM, any differences in the magnitude of this relationship can likely be explained through an examination of frontal plane knee angle during walking. This finding suggests that interventions derived distal to the knee should account for the effect of frontal plane knee angle to have the desired effect on the KAM.

Osteoarthritis year in review 2019: mechanics.

Mechanics play a critical - but not sole - role in the pathogenesis of osteoarthritis, and recent research has highlighted how mechanical constructs are relevant at the cellular, joint, and whole-body level related to osteoarthritis outcomes. This review examined papers from April 2018 to April 2019 that reported on the role of mechanics in osteoarthritis etiology, with a particular emphasis on studies that focused on the interaction between movement and tissue biomechanics with other clinical outcomes relevant to the pathophysiology of osteoarthritis. Studies were grouped by themes that were particularly prevalent from the past year. Results of the search highlighted the large exposure of knee-related research relative to other body areas, as well as studies utilizing laboratory-based motion capture technology. New research from this past year highlighted the important role that rate of exerted loads and rate of muscle force development - rather than simply force capacity (strength) - have in OA etiology and treatment. Further, the role of muscle activation patterns in functional and structural aspects of joint health has received much interest, though findings remain equivocal. Finally, new research has identified potential mechanical outcome measures that may be related to osteoarthritis disease progression. Future research should continue to combine knowledge of mechanics with other relevant research techniques, and to identify mechanical markers of joint health and structural and functional disease progression that are needed to best inform disease prevention, monitoring, and treatment.

Kinetic risk factors of running-related injuries in female recreational runners.

Our objective was to prospectively investigate the association of kinetic variables with running-related injury (RRI) risk. Seventy-four healthy female recreational runners ran on an instrumented treadmill while 3D kinetic and kinematic data were collected. Kinetic outcomes were vertical impact transient, average vertical loading rate, instantaneous vertical loading rate, active peak, vertical impulse, and peak braking force (PBF). Participants followed a 15-week half-marathon training program. Exposure time (hours of running) was calculated from start of program until onset of injury, loss to follow-up, or end of program. After converting kinetic variables from continuous to ordinal variables based on tertiles, Cox proportional hazard models with competing risks were fit for each variable independently, before analysis in a forward stepwise multivariable model. Sixty-five participants were included in the final analysis, with a 33.8% injury rate. PBF was the only kinetic variable that was a significant predictor of RRI. Runners in the highest tertile (PBF < -0.27 BW) were injured at 5.08 times the rate of those in the middle tertile and 7.98 times the rate of those in the lowest tertile. When analyzed in the multivariable model, no kinetic variables made a significant contribution to predicting injury beyond what had already been accounted for by PBF alone. Findings from this study suggest PBF is associated with a significantly higher injury hazard ratio in female recreational runners and should be considered as a target for gait retraining interventions.

Clinical and biomechanical changes following a 4-month toe-out gait modification program for people with medial knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: To compare changes in knee pain, function, and loading following a 4-month progressive walking program with or without toe-out gait modification in people with medial tibiofemoral knee osteoarthritis. DESIGN: Individuals with medial knee osteoarthritis were randomized to a 4-month program to increase walking activity with (toe-out) or without (progressive walking) concomitant toe-out gait modification. The walking program was similar between the two groups, except that the gait modification group was trained to walk with 15° more toe-out. Primary outcomes included: knee joint pain (WOMAC), foot progression angles and knee joint loading during gait (knee adduction moment (KAM)). Secondary outcomes included WOMAC function, timed stair climb, and knee flexion moments during gait. RESULTS: Seventy-nine participants (40 in toe-out group, 39 in progressive walking group) were recruited. Intention-to-treat analysis showed no between-group differences in knee pain, function, or timed stair climb. However, the toe-out group exhibited significantly greater changes in foot progression angle (mean difference = -9.04° (indicating more toe-out), 95% CI: -11.22°, -6.86°; P < 0.001), late stance KAM (mean difference = -0.26 %BW*ht, 95% CI: -0.39 %BW*ht, -0.12 %BW*ht, P < 0.001) and KAM impulse (-0.06 %BW*ht*s, 95% CI: -0.11 %BW*ht*s, -0.01 %BW*ht*s; P = 0.031) compared to the progressive walking group at follow-up. The only between-group difference that remained at a 1-month retention assessment was foot progression angle, with greater changes in the toe-out group (mean difference = -6.78°, 95% CI: -8.82°, -4.75°; P < 0.001). CONCLUSIONS: Though both groups experienced improvements in self-reported pain and function, only the toe-out group experienced biomechanical improvements. TRIALS REGISTRY NUMBER: NCT02019108.

Physiological arousal accompanying postural responses to external perturbations after stroke.

OBJECTIVE: The purpose of this study was to examine simultaneously the level of physiological arousal and the postural response to external perturbations in people post-stroke compared to age-matched controls to build a more comprehensive understanding of the effect of stroke on postural control and balance self-efficacy. METHODS: Participants stood with each foot on separate force platforms. Ten applications of loads of 2% body weight at the hips perturbed the participant anteriorly under two conditions: investigator-triggered or self-triggered (total 20). Electrodermal activity (EDA; measurement of physiological arousal), electromyography (EMG) of the ankle plantarflexor muscles and anterior-posterior center of pressure measurements were taken pre-perturbation (anticipatory) and post-perturbation (response) and compared between the initial (first two) and final (last two) perturbations. RESULTS: Participants post-stroke demonstrated significantly higher levels of anticipatory EDA and anticipatory paretic plantarflexor EMG during both self- and investigator-triggered conditions compared to controls. Anticipatory EDA levels were higher in the final perturbations in participants post-stroke in both conditions, but not in controls. Habituation of the EDA responses post-perturbation was exhibited in the self-triggered perturbations in controls, but not in participants post-stroke. CONCLUSIONS: Physiological arousal and postural control strategies of controls revealed habituation in response to self-triggered perturbations, whereas this was not seen in participants post-stroke. SIGNIFICANCE: Understanding the physiological arousal response to challenges to standing balance post-stroke furthers our understanding of postural control mechanisms post-stroke.

Behavior of medial gastrocnemius motor units during postural reactions to external perturbations after stroke.

OBJECTIVE: This study investigated the behavior of medial gastrocnemius (GM) motor units (MU) during external perturbations in standing in people with chronic stroke. METHODS: GM MUs were recorded in standing while anteriorly-directed perturbations were introduced by applying loads of 1% body mass (BM) at the pelvis every 25-40s until 5% BM was maintained. Joint kinematics, surface electromyography (EMG), and force platform measurements were assessed. RESULTS: Although external loads caused a forward progression of the anterior-posterior centre of pressure (APCOP), people with stroke decreased APCOP velocity and centre of mass (COM) velocity immediately following the highest perturbations, thereby limiting movement velocity in response to perturbations. MU firing rate did not increase with loading but the GM EMG magnitude increased, reflecting MU recruitment. MU inter spike interval (ISI) during the dynamic response was negatively correlated with COM velocity and hip angular velocity. CONCLUSIONS: The GM utilized primarily MU recruitment to maintain standing during external perturbations. The lack of MU firing rate modulation occurred with a change in postural central set. However, the relationship of MU firing rate with kinematic variables suggests underlying long-loop responses may be somewhat intact after stroke. SIGNIFICANCE: People with stroke demonstrate alterations in postural control strategies which may explain MU behavior with external perturbations.

Motor unit recruitment and firing rate in medial gastrocnemius muscles during external perturbations in standing in humans.

There is limited investigation of the interaction between motor unit recruitment and rate coding for modulating force during standing or responding to external perturbations. Fifty-seven motor units were recorded from the medial gastrocnemius muscle with intramuscular electrodes in response to external perturbations in standing. Anteriorly directed perturbations were generated by applying loads in 0.45-kg increments at the pelvis every 25-40 s until 2.25 kg was maintained. Motor unit firing rate was calculated for the initial recruitment load and all subsequent loads during two epochs: 1) dynamic response to perturbation directly following each load drop and 2) maintenance of steady state between perturbations. Joint kinematics and surface electromyography (EMG) from lower extremities and force platform measurements were assessed. Application of the external loads resulted in a significant forward progression of the anterior-posterior center of pressure (AP COP) that was accompanied by modest changes in joint angles (<3°). Surface EMG increased more in medial gastrocnemius than in the other recorded muscles. At initial recruitment, motor unit firing rate immediately after the load drop was significantly lower than during subsequent load drops or during the steady state at the same load. There was a modest increase in motor unit firing rate immediately after the load drop on subsequent load drops associated with regaining balance. There was no effect of maintaining balance with increased load and forward progression of the AP COP on steady-state motor unit firing rate. The medial gastrocnemius utilized primarily motor unit recruitment to achieve the increased levels of activation necessary to maintain standing in the presence of external loads.

Effects of a 10-week toe-out gait modification intervention in people with medial knee osteoarthritis: a pilot, feasibility study.

OBJECTIVE: To examine the feasibility of a 10-week gait modification program in people with medial tibiofemoral knee osteoarthritis (OA), and to assess changes in clinical and biomechanical outcomes. DESIGN: Fifteen people with medial knee OA completed 10 weeks of gait modification focusing on increasing toe-out angle during stance 10° compared to their self-selected angle measured at baseline. In addition to adherence and performance difficulty outcomes, knee joint symptoms (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and total score, numerical rating scale (NRS) of pain), and knee joint loading during gait (late stance peak knee adduction moment (KAM)) were assessed. RESULTS: Participants were able to perform the toe-out gait modification program with minimal to moderate difficulty, and exhibited significant increases in self-selected toe-out angle during walking (P < 0.001). Joint discomfort was reported by five participants (33%) in the hip or knee joints, though none lasted longer than 2 weeks. Participants reported statistically significant reductions in WOMAC pain (P = 0.02), NRS pain (P < 0.001), WOMAC total score (P = 0.02), and late stance KAM (P = 0.04). CONCLUSIONS: These preliminary findings suggest that toe-out gait modification is feasible in people with medial compartment knee OA. Preliminary changes in clinical and biomechanical outcomes provide the impetus for conducting larger scale studies of gait modification in people with knee OA to confirm these findings.

Lateral trunk lean gait modification increases the energy cost of treadmill walking in those with knee osteoarthritis.

OBJECTIVE: To compare the energy expenditure of increased lateral trunk lean walking - a suggested method of reducing medial compartment knee joint load - compared to normal walking in a population of older adults with medial knee osteoarthritis (OA). METHOD: Participants completed two randomly-presented treadmill walking conditions: 15 min of normal walking or walking with ten degrees of peak lateral trunk lean. Lateral trunk lean angle was displayed in front of the participant in real-time during treadmill conditions. Energy expenditure (VO2 and METs), heart rate (HR), peak lateral trunk lean angle, knee pain and perceived exertion were measured and differences between conditions were compared using paired t-tests. RESULTS: Twelve participants (five males, mean (standard deviation (SD)) age 64.1 (9.4) years, body mass index (BMI) 28.3 (4.9) kg/m²) participated. All measures were significantly elevated in the lateral trunk lean condition (P < 0.008), except for knee pain (P = 0.22). Oxygen consumption (VO2) was, on average 9.5% (95% CI 4.2-14.7%) higher, and HR was on average 5.3 beats per minute (95% CI 1.7-9.0 bpm) higher during increased lateral trunk lean walking. CONCLUSION: Increased lateral trunk lean walking on a treadmill resulted in significantly higher levels of steady-state energy expenditure, HR, and perceived exertion, but no difference in knee pain. While increased lateral trunk lean has been shown to reduce biomechanical measures of joint loading relevant to OA progression, it should be prescribed with caution given the potential increase in energy expenditure experienced when it is employed.

Altering foot progression angle in people with medial knee osteoarthritis: the effects of varying toe-in and toe-out angles are mediated by pain and malalignment.

OBJECTIVES: To evaluate if altering the foot progression angle (FPA) by varying magnitudes during gait alters the external knee adduction moment (KAM), knee flexion moment (KFM), knee extension moment (KEM) and/or symptoms in people with medial knee osteoarthritis (OA). Potential influence of pain and knee malalignment on load-modifying effects of FPA was investigated. DESIGN: Participants (n = 22) underwent 3-dimensional gait analysis to measure KAM peaks, KAM impulse, KFM and KEM peaks. Following natural gait, five altered FPA conditions were performed in random order (10° toe-in, 0° FPA, 10° toe-out, 20° toe-out and 30° toe-out). A projection screen displayed their real-time FPA. Pain/discomfort at knees and feet/ankles were evaluated for each condition. Linear mixed models were used for statistical analysis. RESULTS: Toe-in reduced the early stance peak KAM and KEM but increased the KAM impulse, late stance peak and KFM. Toe-out reduced the KAM impulse, late stance peak and KFM (P < 0.001) but increased the early stance peak KAM and KEM. All effects were greater in participants with more varus knees. Pain significantly mediated the effect of altered FPA on the KAM impulse and late stance peak. In more painful individuals, toe-in was predicted to reduce the KAM impulse and late stance peak, and increase them for toe-out gait. There were no immediate symptomatic changes. CONCLUSIONS: Effects of altered FPA vary across all medial knee load parameters and it is difficult to determine an optimal direction of FPA change. Future studies should consider Western Ontario McMaster Universities OA Index (WOMAC) pain to judge the likely effects of altered FPA.

Contralateral cane use and knee joint load in people with medial knee osteoarthritis: the effect of varying body weight support.

OBJECTIVE: To evaluate the effect of varying body weight support (BWS) with contralateral cane use on medial knee load, measured by external knee adduction moment (KAM), in medial knee osteoarthritis (OA) participants. Influences of cane use technique, pain and malalignment on the cane's load-reducing effects were investigated. METHOD: Participants (n=23) underwent three-dimensional gait analysis to measure KAM peaks (early and late stance) and impulse. Unaided walking was firstly analyzed. Following cane use training, participants placed pre-determined magnitudes of BWS through the cane (10%, 15% and 20% in random order), with visual feedback provided via a force-instrumented cane and projection screen. Contributions of cane use technique (peak BWS magnitude and timing, cane impulse (BWS∗time) anterior and lateral cane distance from limb) and Western Ontario McMaster Universities OA Index (WOMAC) pain and malalignment to KAM outcomes were evaluated using linear mixed models. RESULTS: Cane use reduced all KAM variables, with a dose-response effect apparent. Cane BWS impulse was important in reducing the early stance peak KAM (P<0.001), peak BWS for late stance KAM (P<0.001) and both BWS measures for KAM impulse reductions (P<0.001). Variables contributing to efficacy of load-reduction differed across outcomes. Generally, greater reductions were achieved with longer lateral cane distances, peak BWS timing similar to KAM peaks, and shorter anterior cane distances. Greater pain and varus alignment improved load-reduction for some outcomes. CONCLUSION: Contralateral cane use significantly reduced medial knee load, with a dose-response effect. Medial knee OA patients should be encouraged to maintain greater BWS across stance, with cane placement more lateral for optimum benefit.

Hip strengthening reduces symptoms but not knee load in people with medial knee osteoarthritis and varus malalignment: a randomised controlled trial.

OBJECTIVE: To determine whether hip abductor and adductor muscle strengthening reduces medial compartment knee load and improves symptoms in people with medial tibiofemoral OA and varus malalignment. METHODS: In a randomised controlled trial, 89 participants were randomly allocated to a hip strengthening group or to a control group with no intervention. The strengthening group performed a physiotherapist-supervised home exercise program targeting the hip abductor and adductor muscles for 12 weeks. The primary outcome was the peak external knee adduction moment measured using three-dimensional gait analysis by a blinded assessor. Secondary outcomes included a pain numeric rating scale, Western Ontario and McMaster Universities Osteoarthritis Index, step test, stair climb test, maximum isometric strength of hip and quadriceps muscles and participant-perceived rating of overall change. Intention-to-treat analyses were performed using linear regression modelling adjusting for baseline outcomes and other characteristics. RESULTS: The trial was completed by 76/89 participants (85%). There was no significant between-group difference in change in the knee adduction moment [mean difference (95% confidence interval (CI)) 0.134 (-0.069 to 0.337) Nm/BW x HT%]. All pain, physical function and muscle strength measures showed significantly greater improvement in the strengthening group (all P<0.05). The relative risk (95% CI) of participant-perceived overall improvement in the strengthening group compared to the control group was 20.02 (6.21-64.47). CONCLUSIONS: Although strengthening the hip muscles improved symptoms and function in this patient group, it did not affect medial knee load as measured by the knee adduction moment. Thus it is unlikely that hip muscle strengthening influences structural disease progression. TRIAL REGISTRATION: ACTR12607000001493.

Lateral trunk lean explains variation in dynamic knee joint load in patients with medial compartment knee osteoarthritis.

OBJECTIVE: To test the hypothesis that selected gait kinematics, particularly lateral trunk lean, observed in patients with medial compartment knee osteoarthritis explain variation in dynamic knee joint load. METHOD: In this cross-sectional observational study, 120 patients with radiographically confirmed varus gonarthrosis underwent three-dimensional gait analysis at their typical walking speed. We used sequential (hierarchical) linear regression to examine the amount of variance in dynamic knee joint load (external knee adduction moment) explained by static lower limb alignment (mechanical axis angle) and gait kinematics determined a priori based on their proposed effect on knee load (walking speed, toe-out angle, and lateral trunk lean angle). RESULTS: Approximately 50% of the variation in the first peak external knee adduction moment was explained by mechanical axis angle (25%), Western Ontario and McMaster Universities Osteoarthritis Index pain score (1%), gait speed (1%), toe-out angle (12%), and lateral trunk lean angle (13%). There was no confounding or interaction with Kellgren and Lawrence grade of severity. CONCLUSIONS: Gait kinematics, particularly lateral trunk lean, explain substantial variation in dynamic knee joint load in patients with medial compartment knee osteoarthritis. While largely ignored in previous gait studies, the effect of lateral trunk lean should be considered in future research evaluating risk factors and interventions for progression of knee osteoarthritis.

Reproducibility of individualized coronary heart disease risk calculations in patients with diabetes mellitus.

AIMS: To determine prospectively, the reproducibility of individualized coronary heart disease (CHD) risk estimations in a high-risk (diabetic) population. METHODS: One hundred and three patients attending a hospital diabetes clinic who were in the primary prevention category for CHD had measurements of cholesterol, HDL-cholesterol and systolic blood pressure (SBP) performed in one of 13 general practices and then 2 weeks later in the hospital clinic. The data were combined with age, sex, smoking history and diabetic status data to produce a 10-year CHD risk estimate for each occasion using the Framingham algorithm. RESULTS: The coefficients of variation for cholesterol, HDL and SBP were 6.0%, 9.4% and 7.0%, respectively. When classified by treatment thresholds of 15% and 30% 10-year CHD risk, 88% of patients were classified in the same category on both occasions. Kappa values for the 15% and 30% risk thresholds were 0.71 and 0.82. This indicates good interobserver agreement for the estimation of CHD risk. The use of a single BP rather than the mean of two, resulted in seven of 206 estimations of CHD risk performed in 103 patients crossing a risk threshold, with 6/7 being placed in a higher risk category. CONCLUSIONS: Estimation of CHD risk on a single occasion is sufficient to make robust treatment decisions based on risk thresholds. Use of a single BP measurement rather than the mean of two overestimates the risk category in around 3% of cases.

Failure of a 3D conformal boost to improve radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To determine whether the use of 3-dimensional (3D) boost for patients with nasopharynx cancer improves local control and reduces the risk of long-term complications. METHODS AND MATERIALS: From 1988 to 1998, 68 patients with nasopharynx cancer received conventional external beam therapy followed by a 3D boost. Disease characteristics of treated patients were as follows: WHO I histology 7%, WHO II 62%, WHO III 31%, clinical AJCC stage T1--2 45%, T3--4 55%, N0--1 63%, N2--3 37%, M0 100%. The median radiation dose was 70 Gy (68--75.6 Gy). Thirty-five patients (52%) received cisplatin-based chemotherapy. The median follow-up of surviving patients was 42 months (12--118 months). RESULTS: Five-year actuarial local control was 77%, regional control was 97%, progression-free survival was 56%, and overall survival was 58%. Stage was the only identifiable prognostic factor: 5-year progression-free survival was 65% for Stages I--III vs. 40% for Stage IV (p = 0.01). The incidence of Grade 3-4 complications was 25% and included hearing loss, trismus, dysphagia, chronic sinusitis, and cranial neuropathy. These results are comparable to outcomes reported with conventional radiation techniques for similarly staged patients. CONCLUSION: The lack of a major benefit with the 3D boost may be related to the fact that CT planning was only used for a fraction of the total dose. We are now using intensity modulated radiation therapy to deliver the entire course of radiation. Intensity modulated radiation therapy achieves better conformal distributions than conventional 3D planning, allowing dose escalation and increased normal tissue sparing.

Treatment planning and delivery of intensity-modulated radiation therapy for primary nasopharynx cancer.

PURPOSE: To implement intensity-modulated radiation therapy (IMRT) for primary nasopharynx cancer and to compare this technique with conventional treatment methods. METHODS AND MATERIALS: Between May 1998 and June 2000, 23 patients with primary nasopharynx cancer were treated with IMRT delivered with dynamic multileaf collimation. Treatments were designed using an inverse planning algorithm, which accepts dose and dose-volume constraints for targets and normal structures. The IMRT plan was compared with a traditional plan consisting of phased lateral fields and a three-dimensional (3D) plan consisting of a combination of lateral fields and a 3D conformal plan. RESULTS: Mean planning target volume (PTV) dose increased from 67.9 Gy with the traditional plan, to 74.6 Gy and 77.3 Gy with the 3D and IMRT plans, respectively. PTV coverage improved in the parapharyngeal region, the skull base, and the medial aspects of the nodal volumes using IMRT and doses to all normal structures decreased compared to the other treatment approaches. Average maximum cord dose decreased from 49 Gy with the traditional plan, to 44 Gy with the 3D plan and 34.5 Gy with IMRT. With the IMRT plan, the volume of mandible and temporal lobes receiving more than 60 Gy decreased by 10-15% compared to the traditional and 3D plans. The mean parotid gland dose decreased with IMRT, although it was not low enough to preserve salivary function. CONCLUSION: Lower normal tissue doses and improved target coverage, primarily in the retropharynx, skull base, and nodal regions, were achieved using IMRT. IMRT could potentially improve locoregional control and toxicity at current dose levels or facilitate dose escalation to further enhance locoregional control.

In vivo autoradiography of [3H]SCH 39166 in rat brain: selective displacement by D1/D5 antagonists.

The purpose of this study was to examine the receptor occupancy of D1/D5 antagonists for D1-like dopamine receptors in rat brain using [3H]SCH 39166, a highly selective D1/D5 antagonist with low affinity for 5HT2 receptors. A single concentration of triated SCH 39166 was administered to rats, with or without competing doses of the Dl/D5 antagonist SCH 23390 and unlabeled SCH 39166. the D2-like antagonists haloperidol or the 5-HT, antagonist ketanserin. The bound radioactivity in the cortex, striatum, nucleus accumbens and olfactory tubercle was then quantified using an in vivo autoradiographic procedure. The results indicated that [3H]SCH 39166 was dose dependently displaced by the Dl/D5 antagonists in regions associated with both the nigro-striatal pathway and the mesolimbic dopamine pathway, particularly the nucleus accumbens. Neither haloperidol nor ketanserin displaced [3H]SCH 39166 in any of the regions examined. The data were compared with previously published data examining the in vivo binding of [3H]SCH 39166 in rat brain homogenates. The relative values obtained were comparable to values detected in rat brain homogenates after in vivo binding of [3H]SCH 39166.

Prone breast radiotherapy in early-stage breast cancer: a preliminary analysis.

PURPOSE: Women with large breasts have marked dose inhomogeneity and often an inferior cosmetic outcome when treated with breast conservation compared to smaller-sized patients. We designed a prone breast board, which both minimizes breast separation and irradiated lung or heart volume. We report feasibility, cosmesis, and preliminary local control and survival for selected women with Stage 0-II breast cancer. MATERIALS AND METHODS: Fifty-six patients with clinical Stage 0-II breast cancer were treated with lumpectomy and breast irradiation utilizing a prototype prone breast board. A total of 59 breasts were treated. Indications for treatment in the prone position were large or pendulous breast size (n = 57), or a history of cardiopulmonary disease (n = 2). The median bra size was 41D (range, 34D-44EE). Cosmesis was evaluated on a 1-10 (worst-to-best) scale. RESULTS: Acute toxicity included skin erythema (80% of patients experienced Grade I or Grade II erythema), breast edema (72% of patients experienced mild edema), pruritus (20% of patients), and fatigue (20% of patients reported mild fatigue). One patient required a treatment break. The only late toxicity was related to long-term cosmesis. The mean overall cosmesis score for 53 patients was 9.37 (range, 8-10). Actuarial 3- and 5-year local control rates are 98%. Actuarial overall survival at 3 and 5 years are 98% and 94%. CONCLUSION: Our data indicate that treating selected women with prone breast radiotherapy is feasible and tolerated. The approach results in excellent cosmesis, and short-term outcome is comparable to traditional treatment techniques. This technique offers an innovative alternative to women who might not otherwise be considered candidates for breast conservation.

A laryngoscope designed for intubation of the rat.

We successfully intubated 257 rats with a laryngoscope that we designed for this purpose. Orotracheal intubation with this laryngoscope can be performed quickly and without harm to the animal. This instrument provides direct visualization of the vocal cords, allowing rapid, safe intubation of the rat. Maintenance of an adequate airway with endotracheal intubation is superior to tracheostomy for repeated experiments, and therefore this laryngoscope makes such studies easier and safer to perform.

Magnetic motor evoked potential monitoring in the rat.

OBJECT: The authors conducted a study to provide an objective electrophysiological assessment of descending motor pathways in rats, which may become a means for predicting outcome in spinal cord injury research. METHODS: Transcranial magnetic motor evoked potentials (TMMEPs) were recorded under various conditions in awake, nonanesthetized, restrained rats. Normative data were collected to determine the reproducibility of the model and to evaluate the effect of changing the stimulus intensity on the evoked signals. In addition, an experiment was performed to determine if the TMMEPs produced were the result of auditory startle response (ASR) potentials elicited by the sound generated by the movement of the copper coil inside its casing during magnetic stimulation. Transcranial magnetic motor evoked potentials were elicited after magnetic stimulation. At 100% stimulus intensity, the mean forelimb onset latency was 4.2 +/- 0.39 msec, and the amplitude was 9.16 +/- 3.44 mV. The hindlimb onset latency was 6.5 +/- 0.47 msec, and the amplitude was 11.47 +/- 5.25 mV. As the stimulus intensity was decreased, the TMMEP onset latency increased and the response amplitude decreased. The ASR potentials were shown to have longer latencies, smaller amplitudes, and were more variable than those of the TMMEPs. CONCLUSIONS: These experiments demonstrate that TMMEPs can be recorded in awake, nonanesthetized rats. The evoked signals were easy to elicit and reproduce. This paper introduces noninvasive TMMEPs as a new technique for monitoring the physiological integrity of the rat spinal cord.