Inverse treatment planning for an electronic brachytherapy system delivering anisotropic radiation therapy.

An inverse radiation treatment planning algorithm for Sensus Healthcare's SculpturaTM electronic brachytherapy system has been designed. The algorithm makes use of simulated annealing to optimize the conformation number (CN) of the treatment plan. The highly anisotropic dose distributions produced by the SculpturaTM x-ray source empower the inverse treatment planning algorithm to achieve highly conformal treatment plans for a wide range of prescribed planning target volumes. Over a set of 10 datasets the algorithm achieved an average CN of 0.79 ± 0.08 and an average gamma passing rate of 0.90 ± 0.10 at 5%/5 mm. A regularization term that encouraged short treatment plans was used, and it was found that the total treatment time could be reduced by 20% with only a nominal reduction in the CN and gamma passing rate. It was also found that downsampling the voxelized volume (from 3203 to 643 voxels) prior to optimization resulted in a 150× speedup in the optimization time (from 2 + minutes to < 1 s) without affecting the quality of the treatment plan.

Characterization of an x-ray source with a partitioned diamond-tungsten target for electronic brachytherapy with 3D beam directionality.

The Sculptura™ is a new high-dose-rate electronic brachytherapy system developed by Sensus Healthcare. By combining a steerable electron beam with a partitioned diamond-tungsten x-ray target, the x-ray source of the Sculptura™ is capable of producing highly anisotropic dose distributions, thus achieving true 3D beam directionality. This article reports the spectral and dosimetric characterization of the Sculptura™ x-ray source through a combination of measurements and Monte Carlo simulations for operating points between 50-100 kV. Excellent agreement (~5% discrepancy) between the simulations and measurements was obtained for in-air dose rate characterization. The validated simulations were then used to calculate the dose distribution in water. Dose rates of >2 cGy/min/µA can be produced at 100 kV, thus delivering 10 Gy in 1 min for typical operating conditions. The dose distributions are sharply peaked, with a full-width at half-maximum azimuth of about 100°.

Kinematic and experimental investigation of manual resection tools for transurethral bladder tumor resection.

BACKGROUND: Transurethral Resection of Bladder Tumors (TURBT) is a challenging procedure partly due to resectoscope limitations. To date, manual resection performance has not been fully characterized. This work characterizes manual resection performance in the bladder while analyzing the effect of resection location on accuracy. METHODS: Kinematic simulations are used to assess kinematic measures of resection dexterity. An experimental protocol for manual resection accuracy assessment is developed. Cross correlations between the theoretical performance measures and the observed experimental accuracy are investigated. RESULTS: Tangential accuracy correlates relatively strongly with normal singular value and moderately with tangential kinematic conditioning index and tangential minimum singular value. Simulations also clarified difficulties in resecting close to the bladder neck. CONCLUSIONS: Measures to evaluate accuracy and dexterity of TURBT from a kinematic viewpoint are presented to provide a currently missing quantified dexterity baseline in manual TURBT. Limitations in various bladder regions are illustrated. Copyright © 2016 John Wiley & Sons, Ltd.

Use of Contrasted Computerized Tomography as a Surrogate for Nuclear Medicine Renogram to Categorize Renal Function in the Setting of Ureteropelvic Junction Obstruction.

OBJECTIVE: To use basic measurements on contrasted computerized tomography (CT) to reliably determine whether a kidney with ureteropelvic junction obstruction (UPJO) is definitively functional (≥30% differential renal function [DRF]) or nonfunctional (≤10% DRF), obviating the need for nuclear medicine renogram (RG) to determine DRF. METHODS: This is a single institution, retrospective cohort of patients diagnosed with UPJO who underwent either pyeloplasty or nephrectomy between December 2004 and December 2014. Included patients had both preoperative mercaptoacetyltriglycine RG and contrasted CT within 180 days of each other. Patients with stents or nephrostomy tubes were excluded. RESULTS: A total of 49 patients were included. The strongest correlation between differential CT measurements and DRF on RG existed by multiplying the cortical area by the average cortical Hounsfield units (Pearson's r = 0.90, P < .001). Using an equation derived from linear regression and cutoff values generated by receiver operator curve (ROC) analysis, CT equation-estimated DRF values of ≥40% and ≤10% correlated with "definitively functional" RG values of ≥30% (100% specificity) and with "definitively nonfunctional" RG values of ≤10% (100% specificity), respectively. In 30 out of 49 cases, CT could have replaced RG. CONCLUSION: RG is the gold standard in determining quantitative DRF. However, the treatment algorithm for a kidney with symptomatic UPJO hinges on categorized function: "functional" (repair) or "nonfunctional" (remove). Appropriate measurements on contrasted CT can categorize definitively functional or nonfunctional kidneys with UPJO, negating the need for RG to obtain DRF in a majority of cases. This study design favors real-world application with potential to reduce medical expenditure and delay in definitive treatment.

Defining the Rate of Primary Ureteroscopic Failure in Unstented Patients: A Multi-Institutional Study.

PURPOSE: Primary ureteroscopic intervention for kidney or ureteral stones occasionally encounters difficulty with passage of the ureteroscope in the initial procedure. These patients require a second procedure after stenting. We aim to define the contemporary failure rate of primary ureteroscopy (URS) and identify predictive factors that necessitate prestenting. This will assist in preoperative patient counseling, informed consent, and clinical decision-making. MATERIALS AND METHODS: We conducted a multi-institutional retrospective review of 535 unstented patients undergoing primary URS from August 2011 to August 2013. The primary outcome was gaining access to the unstented ureter. RESULTS: The failure rate for accessing the unstented ureter was 7.7% (41/535). The median age of females with primary ureteroscopic failure was significantly lower than in females who had successful ureteroscopic access (34 vs 52 years; p = 0.0041). There was no difference in the median age of males with access vs failure (58 vs 57 years; p = 0.3683). Proximal ureteral stones had the highest failure rate for ureteral access at 18.28% (p = 0.006). On multivariable logistic regression, proximal ureteral stone location remained a significant predictor of failure when compared to renal stones (odds ratio [OR] 3.14, p = 0.006). When including only ureteral stones in the multivariable analysis, stone location in the proximal ureter compared to the distal ureter remained the only significant predictor of access failure (OR 0.24, p = 0.015). CONCLUSIONS: A low overall rate of ureteral access failure in unstented patients is shown. Young female patients and proximal ureteral stones were less likely to be accessed primarily. This study provides information that will help urologists counsel their patients preoperatively regarding their likelihood of failing primary URS necessitating a second procedure. This will also help the patient to make an informed decision during the consent process and may guide urologists on selective prestenting in higher risk patients.

Narcotic Use and Postoperative Doctor Shopping by Patients with Nephrolithiasis Requiring Operative Intervention: Implications for Patient Safety.

PURPOSE: We sought to determine perioperative patterns of narcotic use and the prevalence of postoperative doctor shopping among patients with nephrolithiasis requiring operative management. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive patients residing in Tennessee who required ureteroscopy with laser lithotripsy for nephrolithiasis at a single institution from January to December 2013. Using the Tennessee CSMD (Controlled Substances Medication Database) patients were categorized by the number of postoperative narcotic providers. Doctor shopping behavior was identified as any patient seeking more than 1 narcotic provider within 3 months of surgery. Demographic and clinical characteristics associated with doctor shopping behavior were identified. RESULTS: During the study period 200 eligible patients underwent ureteroscopy with laser lithotripsy for nephrolithiasis, of whom 48 (24%) were prescribed narcotics by more than 1 provider after surgery. Compared to those receiving narcotics from a single provider, patients with multiple narcotic providers were younger (48.1 vs 54.2 years, p <0.001), less educated (high school education or less in 83.3% vs 58.7%, p = 0.014), more likely to have a history of mental illness (37.5% vs 16%, p <0.01) and more likely to have undergone prior stone procedures (66% vs 42%, p <0.01). Additionally, these patients demonstrated more frequent preoperative narcotic use (87.5% vs 63.2%), longer postoperative narcotic use (39.1 vs 6.0 days) and a higher morphine equivalent dose per prescription (44.7 vs 35.2 dose per day, each p <0.001). CONCLUSIONS: Postoperative doctor shopping is common among patients with nephrolithiasis who require operative management. Urologists should be aware of available registry data to decrease the likelihood of redundant narcotic prescribing.

Toward Improving Transurethral Prostate Surgery: Development and Initial Experiments with a Prototype Concentric Tube Robotic Platform.

INTRODUCTION: Despite the potential clinical advantages of holmium laser enucleation of the prostate (HoLEP), there has been reluctance of the urologic community to adopt the procedure, as a result of a perceived steep learning curve. Thus, we sought to design and develop a transurethral endoscopic robotic platform for HoLEP. MATERIALS AND METHODS: We developed a novel transurethral, concentric tube robotic platform for HoLEP. We conducted magnetic tracking experiments to compare movements of the end effectors of the robot with those of a rigid endoscope. Additionally, we tested the robot on an HoLEP simulator and with a human cadaveric prostate to assess its ability to maneuver within a small working space. RESULTS: In the prostate scanning experiment, the area reached by the robot represents a 65% improvement vs the area accessible by a rigid endoscope without tissue deformation. Additionally, the robot performed well within the confines of the prostatic urethra and was able to successfully complete prostate lobe enucleation, on both the HoLEP simulator and with a human cadaveric prostate. CONCLUSIONS: We have developed a concentric tube robotic platform that is passed through a standard endoscope that is capable of producing complex movements of the end effectors. We have shown that these movements of the concentric tube manipulators are capable of performing tasks that may eventually translate into improved ease of performing HoLEP.

Hand-held transendoscopic robotic manipulators: A transurethral laser prostate surgery case study.

Natural orifice endoscopic surgery can enable incisionless approaches, but a major challenge is the lack of small and dexterous instrumentation. Surgical robots have the potential to meet this need yet often disrupt the clinical workflow. Hand-held robots that combine thin manipulators and endoscopes have the potential to address this by integrating seamlessly into the clinical workflow and enhancing dexterity. As a case study illustrating the potential of this approach, we describe a hand-held robotic system that passes two concentric tube manipulators through a 5 mm port in a rigid endoscope for transurethral laser prostate surgery. This system is intended to catalyze the use of a clinically superior, yet rarely attempted, procedure for benign prostatic hyperplasia. This paper describes system design and experiments to evaluate the surgeon's functional workspace and accuracy using the robot. Phantom and cadaver experiments demonstrate successful completion of the target procedure via prostate lobe resection.

Holmium laser enucleation (HoLEP) and photoselective vaporisation of the prostate (PVP) for patients with benign prostatic hyperplasia (BPH) and chronic urinary retention.

OBJECTIVES: To evaluate short-term outcomes of holmium laser enucleation of the prostate (HoLEP) and photoselective vaporisation of the prostate (PVP) in patients with benign prostatic hyperplasia (BPH) and chronic urinary retention (CUR). PATIENTS AND METHODS: A retrospective chart review was performed of all patients with CUR who underwent HoLEP or PVP at our institution over a 3-year period. CUR was defined as a persistent post-void residual urine volume (PVR) of >300 mL or refractory urinary retention requiring catheterisation. RESULTS: We identified 72 patients with CUR who underwent HoLEP and 31 who underwent PVP. Preoperative parameters including median catheterisation duration (3 vs 5 months, P = 0.71), American Urological Association Symptom Index score (AUASI; 18 vs 21, P = 0.24), and PVR (555 vs 473 mL, P = 0.096) were similar between the HoLEP and PVP groups. The HoLEP group had a larger prostate volume (88.5 vs 49 mL, P < 0.001) and higher PSA concentration (4.5 vs 2.4 ng/mL, P = 0.001). At median 6-month follow-up, 71 (99%) HoLEP patients and 23 (74%) PVP patients were catheter-free (P < 0.001). Of the voiding patients, postoperative AUASI (3 vs 4, P = 0.06), maximum urinary flow rate (23 vs 18 mL/s, P = 0.28) and PVR (56.5 vs 54 mL, P = 1.0) were improved in both groups. CONCLUSIONS: Both HoLEP and PVP are effective at improving urinary parameters in men with CUR. Despite larger prostate volumes, HoLEP had a 99% successful deobstruction rate, thus rendering patients catheter-free.

Image-guided surgery and emerging molecular imaging: advances to complement minimally invasive surgery.

Recent technologic advances have ushered in an era of surgery with a focus on development of minimally invasive surgical techniques. Specifically, robotic platforms, with robotic-assisted instrumentation, have helped overcome previous barriers to widespread adoption of laparoscopic surgery. Along these lines, image guidance will soon be incorporated into many laparoscopic/robotic procedures to improve surgeon ease, accuracy, and comfort with these complex operations. Thus, we explore recent advances in image-guided surgery and emerging molecular imaging technologies for minimally invasive urologic surgery.

Efficacy of holmium laser enucleation of the prostate in patients with non-neurogenic impaired bladder contractility: results of a prospective trial.

OBJECTIVE: To examine the outcomes of men with detrusor underactivity or acontractility undergoing holmium laser enucleation of the prostate (HoLEP). METHODS: A prospective case series between 2009 and 2012 was performed to examine short-term outcomes of men with urodynamic evidence of detrusor hypocontractility or acontractility because of a non-neurogenic etiology and concurrent benign prostatic obstruction (BPO), undergoing HoLEP. RESULTS: Fourteen patients with detrusor hypocontractility and 19 patients with acontractility and evidence of BPO underwent HoLEP during the study period. Median age was 71.5 and 75 years, respectively. Preoperatively, 5 (35.7%) men with hypocontractility and 19 (100%) men with acontractility had catheter-dependent urinary retention for a median of 3 and 9 months, respectively. At a median follow-up of 24.7 months, all 5 (100%) men with hypocontractility and 18 of 19 (94.7%) men with acontractility were voiding spontaneously without the need for intermittent catheterization. Individuals with hypocontratile bladders had statistically significant improvements in American Urological Association Symptom Index (21.5 vs 3; P = .014), maximum urine flow (Qmax, 10 vs 21 mL/s; P = .001), and postvoid residual (250 vs 53 mL; P = .007) from baseline to postoperative assessments. In patients with an acontractile bladder, 15 of 19 (78.9%) displayed significant return of detrusor contractility, whereas 4 of 19 (21.1%) were voiding exclusively by Valsalva effort on follow-up urodynamic study. Postoperatively, patient satisfaction, as ascertained by American Urological Association Symptom Index, was high for both groups. CONCLUSION: Intermediate follow-up results indicate that HoLEP is a viable management option for men with BPO and detrusor hypocontractility. Furthermore, detrusor acontractility does not appear to adversely affect postoperative results, with return of spontaneous urination and demonstration of detrusor contractility allowing for efficient voiding, in over 95% of patients.

Operational characteristics of (11)c-choline positron emission tomography/computerized tomography for prostate cancer with biochemical recurrence after initial treatment.

PURPOSE: We examined the performance of (11)C-choline positron emission tomography/computerized tomography for its ability to delineate prostate cancer distribution and extent after initial therapy. MATERIALS AND METHODS: A consecutive series retrospective review was performed of all patients with prostate cancer who were evaluated using (11)C-choline positron emission tomography/computerized tomography from September 2007 to November 2010 at the Mayo Clinic. Statistical analysis was performed to determine the sensitivity, specificity, positive predictive value, negative predictive value and prostate specific antigen threshold for the detection of recurrent lesions. RESULTS: In the study period 176 patients with biochemical recurrence after primary treatment failure underwent (11)C-choline positron emission tomography/computerized tomography. Using patient based analysis (11)C-choline positron emission tomography yielded a sensitivity, specificity, positive predictive value and negative predictive value of 93%, 76%, 91% and 81%, respectively. Of the 176 positron emission tomography/computerized tomography scans performed 56 (32%) were deemed clinically useful as defined by the ability to identify lesions not delineated using conventional imaging, thereby prompting changes in clinical management. The optimal prostate specific antigen for lesion detection was 2.0 ng/ml. On multivariate analysis prostate specific antigen at positron emission tomography (HR 1.37, p = 0.04) and clinical stage at initial diagnosis of prostate cancer (HR 5.19, p = 0.0035) were significant predictors of positive (11)C-choline positron emission tomography/computerized tomography. CONCLUSIONS: (11)C-choline positron emission tomography/computerized tomography performs well in men with biochemical recurrence after primary treatment failure. The optimal prostate specific antigen value for lesion detection is approximately 2.0 ng/ml. We found that (11)C-choline positron emission tomography/computerized tomography substantially enhances the rate of prostate cancer lesion detection by approximately 32% beyond what can be garnered using conventional imaging techniques and at a lower prostate specific antigen value.

Robot-assisted sacrocolpopexy: description and video.

Pelvic organ prolapse is a common problem faced by many women, resulting in significant morbidity and negatively impacting quality of life. Sacrocolpopexy can treat women with vaginal vault prolapse, multicompartment prolapse, and/or a history of failed prolapse procedures. The transabdominal sacrocolpopexy has been shown, on multiple studies, to have one of the highest long-term success rates for repair of severe vault prolapse. The goals of surgical repair of vaginal vault prolapse include restoration of proper anatomy, maintenance of sexual function, and durability. Recently, there has been a push toward decreasing morbidity and recovery time associated with operative repair. Therefore, the robot-assisted sacrocolpopexy was developed and has gained widespread acceptance, given the excellent reproducible results, minimal complications, and high patient satisfaction. Our technique for robot-assisted sacrocolpopexy is presented.

20-Year survival after radical prostatectomy as initial treatment for cT3 prostate cancer.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Despite a lack of randomised controlled trials, most men with locally advanced prostate cancer are recommended to undergo external beam radiotherapy (EBRT), often combined with long-term androgen-deprivation therapy (ADT). Many of these men are not offered radical prostatectomy (RP) by their treating urologist. Additionally, it is know that EBRT with long-term ADT does provide good cancer control (88% at 10 years). We have previously published intermediate-term follow-up of a large series of men treatment with RP for cT3 prostate cancer. We report long-term follow-up of a large series of men treated with RP as primary treatment for cT3 prostate cancer. Our study shows that with long-term follow-up RP provides excellent oncological outcomes even at 20 years. While most men do require a multimodal treatment approach, many men can be managed successfully with RP alone. OBJECTIVE: • To present long-term survival outcomes after radical prostatectomy (RP) for patients with cT3 prostate cancer, as the optimal treatment for patients with clinical T3 prostate cancer is debated. PATIENTS AND METHODS: • We identified 843 men who underwent RP for cT3 tumours between 1987 and 1997. • Survival was estimated using the Kaplan-Meier method. • Cox proportional hazards regression models were used to evaluate the association of clinicopathological features with outcome RESULTS: • The median (range) postoperative follow-up was 14.3 (0.1-23.5) years. • Down-staging to pT2 disease occurred in 26% (223/843) at surgery. • Local recurrence-free, systemic progression-free and cancer-specific survival for men with cT3 prostate cancer after RP was 76%, 72%, and 81%, respectively, at 20 years. • On multivariate analysis, increasing RP Gleason score (hazard ratio [HR] 1.8; P = 0.01), non-diploid chromatin content (HR 1.8; P = 0.01), positive surgical margins (HR 2.1; P = 0.007), and seminal vesicle invasion (HR 2.1; P = 0.005) were associated with a significant risk of prostate cancer death, while a more recent year of surgery was associated with a decreased risk of cancer-specific mortality (HR 0.88; P = 0.01) CONCLUSIONS: • RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow-up presented here. • RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumours.

Renal function outcomes in patients treated with partial nephrectomy versus percutaneous ablation for renal tumors in a solitary kidney.

PURPOSE: Partial nephrectomy is the recommended management for small renal masses. Percutaneous ablation is safe and effective with comparable short-term cancer specific survival. Currently to our knowledge data are lacking on the impact of thermal ablation on renal function preservation. We examined the impact on renal function of partial nephrectomy vs percutaneous ablation in patients with a solitary kidney. MATERIALS AND METHODS: We performed a retrospective review to identify patients with a solitary kidney who underwent partial nephrectomy or percutaneous ablation at Mayo Clinic Rochester between 2003 and 2009. Preoperative characteristics and 3-month posttreatment renal function were compared using the Wilcoxon rank sum, chi-square and Fisher exact tests. RESULTS: During the study period 50 patients underwent percutaneous ablation and 62 underwent partial nephrectomy. At partial nephrectomy no ischemia was used in 30 cases (48%), a median of 28 minutes of cold ischemia was used in 26 (42%) and a median of 18 minutes of warm ischemia was used in 6 (10%). Patients who underwent partial nephrectomy were younger (median age 62.5 vs 68.5 years, p = 0.01) and harbored larger tumors (median 3.5 vs 2.5 cm, p = 0.005) with higher nephrometry scores (median 9 vs 7, p = 0.03). At 3-month posttreatment followup no differences were noted between the 2 groups in glomerular filtration rate (p = 0.91), change in glomerular filtration rate (p = 0.77) or change in chronic kidney disease stage (p = 0.87). Similar results were observed when adjusting for age, tumor size and nephrometry score on multivariate analysis. CONCLUSIONS: With judicious use of ischemia partial nephrectomy, even for more complex tumors, has short-term renal function outcomes similar to those of percutaneous ablation.

Does body mass index "dilute" the predictive property of prostate-specific antigen for tumor volume at radical prostatectomy?

OBJECTIVE: To evaluate the effect of the body mass index (BMI) as it relates to the predictive value of the preoperative prostate-specific antigen (PSA) level regarding the tumor volume at radical prostatectomy. Stage migration with the widespread use of PSA screening is well documented; however, the association between the PSA level and tumor volume is less defined. Additionally, the effect of obesity on the serum PSA level might cause relative hemodilution and account for the decreased predictive ability of the PSA level to determine the tumor volume in the modern era. METHODS: We identified 14 293 patients who had undergone radical prostatectomy for prostate cancer from 1987 to 2007 and had a documented BMI. Using the clinicopathologic variables, we examined the relationship among the BMI, preoperative PSA level, and tumor volume at radical prostatectomy using multiple linear regression analysis. RESULTS: An elevated BMI was associated with an increased pathologic Gleason score (P < .0001), increased tumor volume (P < .0001), and increased prostate size (P < .0001). The preoperative PSA level correlated significantly with the tumor volume (P < .0001). No significant correlation was found between the BMI and preoperative PSA level (P = .39). On multivariate analysis, controlling for the BMI, the preoperative PSA level remained a significant predictor of the tumor volume (P < .0001). The interaction between the preoperative PSA level and BMI in the prediction of the tumor volume was not statistically significant (P = .56), suggesting that the BMI does not affect the association between the PSA level and tumor volume. CONCLUSION: Our results have shown that the predictive ability of the PSA level for tumor volume is not affected by the BMI. There does not appear to be a need to correct the serum PSA level in relation to the BMI when used in preoperative prediction models of the tumor volume.

A novel technique for the repair of urostomal hernias using human acellular dermal matrix.

OBJECTIVE: To report a new technique to reconstruct the abdominal wall at the site of the hernia with 2 separate layers of human acellular dermal matrix (hADM). Parastomal hernia is the most commonly encountered complication of ileal conduit urinary diversion, occurring at a rate of 5%-25%. Multiple methods of parastomal hernia repair, including primary fascial repair, mesh repair, and stoma resiting have been reported, with a wide variety of approaches and materials being used. METHODS: Between 2008 and 2009, 4 patients underwent surgical repair of urostomal hernias using hADM (LifeCell, Branchburg, NJ). All were operated on by a single surgeon using a standard technique of open repair whereby the posterior and anterior rectus fascia at the stoma site were reconstructed with hADM. Demographic data, preoperative and intraoperative risk factors, immediate postoperative complications, and hernia recurrence were collected and analyzed. RESULTS: Four patients underwent urostomal hernia repair with Alloderm without intraoperative complications. Mean operative time was 261.25 ± 80.8 minutes. Mean hospital stay was 9 ± 3 days. With an average of 270 ± 104-days' follow-up, there were no recurrent hernias detected. CONCLUSIONS: In patients with urostomal hernia, reconstruction of the stoma site and abdominal wall with hADM appears to be a safe and effective management solution and avoids the difficulty with relocating the urostomy or placing prosthetic material in the site.

Effect of body temperature during exercise on skeletal muscle cytochrome c oxidase content.

This study determined the role of body temperature during exercise on cytochrome-c oxidase (CytOx) activity, a marker of mitochondrial content, and mitochondrial heat shock protein 70 (mtHSP70), which is required for import of nuclear-coded preproteins. Male, 10-wk-old, Sprague-Dawley rats exercised identically for 9 wk in ambient temperatures of 23 degrees C (n = 10), 8 degrees C with wetted fur (n = 8), and 4 degrees C with wetted fur and fan (n = 7). These conditions maintained exercising core temperature (T(c)) at 40.4, 39.2, or 38.0 degrees C (resting temperature), respectively. During weeks 3-9, exercisers ran 5 days/wk up a 6% grade at 20 m/min for 60 min. Animals were housed at 23 degrees C. Gastrocnemius CytOx activity in T(c)=38.0 degrees C (83.5 +/- 5.5 microatoms O x min(-1) x g wet wt(-1)) was greater than all other groups (P < 0.05), exceeding sedentary (n = 7) by 73.2%. T(c) of 40.4 and 39.2 degrees C also were higher than sedentary by 22.4 and 37.4%, respectively (P < 0.05). Quantification of CytOx content verified that the increased activity was due to an increase in protein content. In extensor digitorum longus, a nonactive muscle, CytOx was not elevated in T(c) = 38.0 degrees C. mtHSP70 was significantly elevated in gastrocnemius of T(c) = 38.0 degrees C compared with sedentary (P < 0.05) but was not elevated in extensor digitorum longus (P > 0.05). The data indicate that decreasing exercise T(c) may enhance mitochondrial biogenesis and that mtHSP70 expression is not dependent on temperature.