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Cerebral hemodynamics have been quantified during exercise via transcranial Doppler ultrasound, as it has high-sensitivity to movement artifacts and displays temporal superiority. Currently, limited research exists regarding how different exercise modalities and postural changes impact the cerebrovasculature across the cardiac cycle. Ten participants (4 females and 6 males) ages 20-29 completed three exercise tests (treadmill, supine, and upright cycling) to volitional fatigue. Physiological data collected included middle cerebral artery velocity (MCAv), blood pressure (BP), heart rate, and respiratory parameters. Normalized data were analyzed for variance and effect sizes were calculated to examine differences between physiological measures across the three exercise modalities. Systolic MCAv was greater during treadmill compared to supine and upright cycling ( p  < 0.001, (large) effect size), and greater during upright versus supine cycling ( p  < 0.017, (large)). Diastolic MCAv was lower during treadmill versus cycling exercise only at 60% maximal effort ( p  < 0.005, (moderate)) and no differences were observed between upright and supine cycling. No main effect was found for mean and diastolic BP ( p  > 0.05, (negligible)). Systolic BP was lower during treadmill versus supine cycling at 40% and 60% intensity ( p  < 0.05, (moderate-large)) and greater during supine versus upright at only 60% intensity ( p  < 0.003, (moderate)). The above differences were not explained by partial pressure of end-tidal carbon dioxide levels (main effect: p  = 0.432) . The current study demonstrates the cerebrovascular and cardiovascular systems respond heterogeneously to different exercise modalities and aspects of the cardiac cycle. As physiological data were largely similar between tests, differences associated with posture and modality are likely contributors., Competing Interests: The authors declare they have no conflicts of interest.

There are differences within the literature regarding the upper frequency cut-off point of the dynamic cerebral autoregulation (CA) high-pass filter. The projection pursuit regression approach has demonstrated that the upper frequency limit is ∼0.07 Hz, whereas another approach [transfer function analysis (TFA) phase approaching zero] indicated a theoretical upper frequency limit for the high-pass filter of 0.24 Hz. We investigated how these limits accurately represent the CA upper frequency limit, in addition to extending earlier findings with respect to biological sexes and across the cardiac cycle. Sixteen participants (nine females and seven males) performed repeated squat-stand manoeuvres at frequencies of 0.05, 0.10, 0.15, 0.20 and 0.25 Hz, with insonation of the middle and posterior cerebral arteries. Linear regression modelling with adjustment for sex and order of squat completion was used to compared TFA gain and phase with 0.25 Hz (above the theoretical limit of CA). The upper frequency limit of CA with TFA gain was within the range of 0.05-0.10 Hz, whereas TFA phase was within the range of 0.20-0.25 Hz, and consistent between vessels, between sexes and across the cardiac cycle. Females displayed greater middle cerebral artery gain compared with males (all P < 0.047), and no phase differences were present (all P > 0.072). Although sex-specific differences were present for specific TFA metrics at a given frequency, the upper frequency limit of autoregulation was similar between cerebral conduit vessels, cardiac cycle phase and biological sex. Future work is warranted to determine whether an upper frequency limit exists with respect to hysteresis analyses., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Sport-related concussion (SRC) can impair the cerebrovasculature both acutely and chronically. Transcranial Doppler (TCD) ultrasound assessment has the potential to illuminate the mechanisms of impairment and provide an objective evaluation of SRC. The current systematic review investigated studies employing TCD ultrasound assessment of intracranial arteries across three broad categories of cerebrovascular regulation: neurovascular coupling (NVC), cerebrovascular reactivity (CVR), and dynamic cerebral autoregulation (dCA). The current review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42021275627). The search strategy was applied to PubMed, as this database indexes all biomedical journals. Original articles on TCD for athletes with medically diagnosed SRC were included. Title/abstract and full-text screening were completed by three authors. Two authors completed data extraction and risk of bias using the Methodological Index for Non-Randomized Studies and Scottish Intercollegiate Guideline Network checklists. Of the 141 articles identified, 14 met the eligibility criteria. One article used an NVC challenge, eight assessed CVR, and six investigated dCA. Methodologies varied widely among studies, and results were heterogeneous. There was evidence of cerebrovascular impairment in all three domains roughly 2 days post-SRC, but the magnitude and recovery of these impairments were not clear. There was evidence that clinical symptom resolution occurred before cerebrovascular function, indicating that physiological deficits may persist despite clinical recovery and return to play. Collectively, this emphasizes an opportunity for the use of TCD to illuminate the cerebrovascular deficits caused by SRC. It also highlights that there is need for consistent methodological rigor when employing TCD in a SRC population.

Unlabelled: To assess whether oncological outcomes are compromised by adopting the curtain dissection (CD) technique (high incision of the peri-prostatic fascia) during nerve-preserving radical prostatectomy (RP)., Patients and Methods: In all, 973 laparoscopic RPs (LRPs) were performed or supervised by one surgeon between March 2000 and October 2007 for cT1-3 N0M0 prostate cancer, of which 510 included bilateral neurovascular bundle preservation. A CD technique was used in 240 men and a standard dissection (StD) technique was used in 270, considered the control group. The technique was extraperitoneal, used five ports and included preservation of the seminal vesicle tips. Thermal energy was not used posterior or lateral to the prostate in either group. Patient, operative and oncological outcome variables were compared using an independent-sample t-test if continuous or with Fisher's exact test for rates., Results: Patient and cancer characteristics before LRP were similar for the CD and StD groups, and there were no significant perioperative differences either. Positive margins occurred in 11.7% of the CD group and 11.1% of the StD group (P = 0.95). At a mean (range) follow-up of 11.7 (3-24) months for the CD group and 13.1 (3-24) months for the StD group, biochemical recurrence rates were 0% and 1.1%, respectively (P = 0.30). Potency (CD, 62%; StD, 61%; P = 0.89) and continence rates (StD, 97%; CD, 98%; P = 0.83) were comparable between the groups, but there was a statistically significant earlier return to continence in the CD group (P < 0.001 at 3 months)., Conclusions: For carefully selected men there appears to be no compromise in cancer control with intrafascial dissection in the short term. However, equally there appears to be no significant improvement in potency after LRP. The earlier return to continence after intrafascial nerve-sparing suggests reduced dissection of periurethral supports rather than preservation of additional autonomic nerve fibres.

Objective: To address concerns about the impact of training on patient outcomes during the 'learning curve' for laparoscopic radical prostatectomy (LRP), we compare the results of our patients undergoing LRP with and without trainees performing a substantial proportion of the cases., Patients and Methods: In all, 771 consecutive cases of LRP were performed or supervised by one surgeon during a 7.5-year period, of which 114 (15%) were training cases. A five-port transperitoneal technique was used in the first 111 patients and an extraperitoneal approach in the remaining 660. Patient, operative and oncological outcome variables were compared using an independent samples t-test if continuous or with Fisher's exact test for rates., Results: There were no differences in preoperative patient or cancer characteristics with the exception of body mass index (BMI) which was lower in the training cases (medians 25 and 26 kg/m(2), P = 0.02) and patient age which was higher (medians 64 and 62 years, P < 0.001). Operative time, which was longer in training cases (medians 200 and 175 min, P < 0.001) was the only significantly different operative variable between the groups. There were no statistically significant differences in postoperative (duration of catheterization, hospitalization time, complication rates, biochemical recurrence and pad-free rates at 1 year) or pathological (gland weight, positive surgical margin rate) outcomes between the groups. As Fellows did not perform the posterior or apical dissection steps in nerve-sparing cases, no evaluation of potency outcomes is included., Conclusions: Training cases took a median of 25 min longer to complete than non-training cases. However, other perioperative measures, complications rates and cancer outcomes were similar. Adequately supervised training in LRP does indeed take additional time but is essential for the dissemination of surgical skills and preservation of acceptable outcomes.

Objective: To report the initial experience of one surgeon, with contemporary experience of both open radical prostatectomy (ORP) and reconstructive laparoscopy, in laparoscopic radical prostatectomy (LRP) in 1000 patients, and to investigate the rate of change of various outcome variables for this procedure with time., Patients and Methods: Between March 2000 and December 2007, 1000 consecutive patients with clinical stage T < or = 3aN0M0 prostate cancer underwent LRP, either supervised (17%) or performed (83%), by one surgeon. The median prostate-specific antigen (PSA) level was 7.0 (1-50) ng/mL and median Gleason sum 6 (4-10); the clinical stage was T1 in 46.9%, T2 in 49.8% and T3 in 3.3%., Results: The median (range) operative duration was 177 (78-600) min. There was one conversion (patient 8) to open surgery. The median blood loss was 200 (10-1300) mL and four patients were transfused (0.4%). The median postoperative hospital stay was 3.0 (3-28) nights. The median catheterization time was 10.0 (0.8-120) days. There were 48 complications (4.8%) requiring surgical intervention in 33 (3.3%) patients, 58% of these as a day-case admission. The positive margin rates according to d'Amico risk groups were: low, 9.1%; intermediate, 20.3%; and high, 36.8%. The overall positive margin rate was 13.3%. The PSA level was < or =0.1 mg/L at 3 months in 99.1% of patients. At a mean follow-up of 27.7 (3-72) months, 96.1% of patients were free of biochemical recurrence. In patients with a follow-up of > or =24 months potency rates peaked in the series at 86% for all men and 94% for men aged < or =65 years, and continence rates at 98% before declining thereafter in men with a shorter follow-up., Conclusion: The learning curve for operating time and blood loss was overcome within the first 100-150 cases, but complication and continence rates took 150-200 cases to reach a plateau. The longest learning curve was for potency, which did not stabilize until 700 cases. These learning curves are likely to be considerably shorter when surgeons are taught in departments with a high throughput of cases but both surgeons and patients should be aware of them. In view of these findings, the authors recommend that LRP should not be self-taught and should be learned within an immersion teaching programme. Even then, a large surgical volume is likely to be needed to maintain clinical outcomes at the highest level.

The present review addresses strategies to preserve prostate health, tackling the three most common prostatic problems with which men present to physicians, namely, prostate hypertrophy, prostatitis and prostate cancer. Unfortunately since a clear etiology does not exist for each of these problems, we have to rely on experimental research, epidemiologic and clinical data to design prevention strategies. A number of modifiable targets have been identified and some are cross-shared between these three very prevalent entities. However, since the pathogenesis of each condition seems multifactorial, and the interconnections between them inadequately understood, chemopreventive strategies are still in their infancy even after very large clinical trials -which produced often more questions than they delivered answers- have already been performed., (Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.)

The role of nephrectomy in the setting of metastatic renal cell carcinoma has long been controversial and has continued to evolve over the last two decades. The practice of cytoreductive nephrectomy has only recently been widely accepted following the publication of 2 large multi-center randomized controlled trials that established a survival benefit for those patients undergoing nephrectomy followed by interferon treatment. Half a decade later, the new paradigm looks set to be questioned with the rapid emergence of tyrosine kinase inhibitors (TKIs). This article reviews the evolution of cytoreductive nephrectomy and speculates on its role in the new frontier of molecular targeting for metastatic renal cell carcinoma.

Objective: To assess the effect on potency recovery of incorporating a high incision of the lateral prostatic fascia (LPF) or curtain dissection (CD) into our technique of laparoscopic nerve-sparing radical prostatectomy (LNSRP)., Patients and Methods: In all, 137 bilateral neurovascular bundle (NVB) preserving LNSRPs were performed, incorporating curtain dissection (CD) of the LPF. Potency was assessed at 1, 3, 6 and 12 months using validated questionnaires and compared with a control group (CG) of standard NVB preservation., Results: There were no conversions to open surgery in either group. The median operative duration in the CD group and the CG was 178 min and 174 min (P = 0.04), blood loss was 300 mL and 200 mL (P = 0.01), and the positive margin rate was 16.1% and 24.1% (P = 0.04), respectively. At a mean follow-up of 5.8 months in the CD group and 28.2 months in the CG, potency rates were 21.1% and 8.8% at 1 month (P = 0.01), and 68.4% and 67.2% at 12 months (P = 1.00), respectively., Conclusion: The potency rate was significantly higher in the CD group at 1 month than in the CG, thereafter the rates were similar between the groups. We think that the merit of this technique is in improved visualization of the basal prostatic contour during antegrade NVB dissection, rather than preserving important nerve fibres. This may explain the lower basal positive margin rate in the CD group of 0% vs 5.8% in the CG (P = 0.007).

Purpose: We quantified the additional benefit of routinely adding 4 lateral biopsies to the initial sextant and transrectal ultrasound lesion targeted biopsy pattern in terms of cancer detection. We related this to costs., Materials and Methods: Prospective data were accrued on 1,010 consecutive patients referred for initial transrectal ultrasound directed prostate biopsy between June 16, 2000 and September 1, 2005. Costs were estimated for the pathology and clinical departments in terms of staff time., Results: Of 1,010 patients 494 (48.9%) were diagnosed with prostate adenocarcinoma. In these cases 411 cancers (83%) were found in medial samples, including 107 (22%) isolated to medial cores alone and 304 (62%) in medial and lateral cores. Only 55 patients (5.4%) had cancer isolated to systematic lateral cores. Of these cancers 30 (3%) were defined as clinically significant based on Gleason grade 7 or greater, or Gleason grade 6 involving more than 5% of any core. There was a 24% increase in biopsy related costs and a 36% increase in pathology costs associated with the 4 additional lateral biopsies., Conclusions: Medial sextant and targeted biopsy directed at transrectal ultrasound identified lesions detects 94.6% of the prostate cancer that is detected with a 10 core biopsy protocol. The latter detects an extra 3% of clinically significant prostate cancer, while increasing costs by 30%. It is important to consider the absolute benefits of systematic lateral prostate biopsy in light of this additional expense when selecting an appropriate transrectal ultrasound biopsy regimen for a patient suspected of harboring prostate cancer.

The efficacy of tamsulosin at the cost of a relatively benign side effect profile has been attributed to receptor selectivity directed at the alpha(1a) and alpha(1d) adrenergic receptor subtypes. The oral-controlled absorption system (OCAS((R))) represents a drug delivery refinement that incorporates a matrix of gel-forming and gel-enhancing agents to promote a constant drug release independent of environmental food or fluid. There are clinical data to support the concept that drug peaks are lessened and that drug release continues throughout the alimentary tract due to the OCAS formulation. Furthermore this equates with less adverse effects on physiologic parameters. To date however improvements in cardiovascular symptoms such as dizziness, headache and syncope have not been demonstrated in healthy men. Ejaculatory dysfunction appears less problematic with the OCAS preparation. Tamsulosin OCAS may be of greatest benefit to men with cardiovascular co-morbidities taking anti-hypertensive medications that might predispose them to symptomatic hypotensive episodes. It will be necessary to evaluate this group of men more closely in further trials to determine what they stand to gain from changing medications, and then relate this to drug costs to draw a final conclusion as to the place of tamsulosin OCAS in contemporary urological practice.

The advent of molecularly targeted agents is rapidly changing the management of metastatic renal cell carcinoma. A case in which surgical metastatectomy was used in the setting of dramatic but incomplete disease response to sunitinib is presented. Some of the issues complicating operative intervention in the setting of multitargeted tyrosine kinase inhibitors are discussed.

Objective: To determine whether preoperative pelvimetry based on computed tomography (CT) can be used to predict technical difficulties during open radical prostatectomy (RP)., Patients and Methods: An open RP database accrued prospectively between January 1997 and June 2005 was used to identify 450 patients with preoperative pelvic imaging. Of these, 165 had adequate imaging of the pelvis with CT to allow pelvimetry using software provided with the medical imaging records. Several pelvic measurements were recorded in conjunction with body mass index and transrectal ultrasonographic estimates of prostatic volume. Outcome measures used to reflect technical surgical difficulties included operative duration, blood transfusion requirements within 30 days of RP, the pathological positive surgical margin and prostatic capsular breech rate. Logistic and linear regression analyses were used to determine the relationship between variables before and after RP., Results: The selected pelvimetric measurements failed to predict either operative duration or the peri-operative blood transfusion requirement. Prostatic volume was predictive of operative duration; for every increase of 20 mL in prostate volume the duration increased by 8.4 min. Although pelvimetric measures failed to predict positive surgical margins at pathology, the transverse diameter predicted the likelihood of a positive margin due to capsular breech. With every 8.6 mm (1 sd) decrease in transverse diameter, the odds of a capsular breech resulting in positive surgical margins increased 5.3 times (95% confidence interval 2.1-20.0, P = 0.002)., Conclusions: Although the "hostile pelvis" influences the likelihood of prostatic capsular breech resulting in positive surgical margins, CT pelvimetric screening of patients before RP is unlikely to be cost-effective. Routine pelvic CT in the evaluation of patients before RP is not supported.

Purpose: In light of a recent tendency toward systematic nontargeted biopsy we reassessed whether identification and biopsy of ultrasonographically suspicious lesions contribute to the detection of prostate cancer., Materials and Methods: We reviewed prospectively gathered data on 7,426 transrectal ultrasound directed prostatic biopsies performed at our institution between June 16, 2000 and September 1, 2005. Patients underwent systematic biopsy (6 to 10 cores on initial biopsy and 13 to 15 on rebiopsy) with additional sampling of visible suspicious lesions. The RR for finding cancer in transrectal ultrasound positive and negative patients was calculated for likely independent prognostic variables., Results: A total of 3,828 biopsies (51.5%) were transrectal ultrasound negative and 3,598 (48.5%) were transrectal ultrasound positive. Prostate cancer was detected in 3,258 biopsies (43.9%). For each independent variable the RR for prostate cancer was higher if a sonographic lesion was present. A lesion increased the likelihood of cancer detection (57.8% vs 30.8%, RR 1.8). Biopsies from lesions identified by transrectal ultrasound had a greater median percent of the core involved with cancer (50% vs 10%, p <0.001) and they were more likely to have Gleason score 7 or greater (69.3% vs 28.3%, p <0.001)., Conclusions: Biopsies taken when a prostatic lesion is identified by transrectal ultrasound are almost twice as likely to show cancer than when no lesion is visible. These cancers are of higher grade and volume and, therefore, they are more clinically significant. The search for and targeted biopsy of suspicious lesions seen on transrectal ultrasound remains important for prostate cancer diagnosis.

Objectives: To compare the alternative energy sources of the holmium:yttrium-aluminum-garnet laser and bipolar plasmakinetic energy for endoscopic enucleation., Methods: A prospective, randomized controlled trial was undertaken, with 20 patients assigned to each group. The preoperative and postoperative measures included transrectal ultrasound-assessed prostate volume, postvoid residual urine volume, and urodynamic evaluation findings. The intraoperative measures included procedure length, energy use, and specimen weight. All adverse events were recorded at each postoperative visit in a 1, 3, 6, and 12-month protocol., Results: No differences were found in the preoperative characteristics between the two groups. The significant differences favoring holmium laser enucleation of the prostate compared with plasmakinetic enucleation of the prostate were seen in the operative time (43.6 versus 60.5 minutes), recovery room time (47.1 versus 65.6 minutes), and bladder irrigation requirement (5% versus 35%). The outcomes after holmium laser enucleation of the prostate and plasmakinetic enucleation of the prostate were in all other respects similar by the postoperative outcome measures assessed., Conclusions: Plasmakinetic enucleation of the prostate is a safe and technically feasible procedure for the enucleation of prostatic adenomata. Plasmakinetic enucleation of the prostate is limited by the longer operative and recovery room times, as well as a more pronounced postoperative irrigation requirement because of reduced visibility and a greater propensity for bleeding. The transfusion rates and catheterization and hospitalization times were similar. The optimal energy source for enucleation should still be considered the holmium laser, but bipolar energy can be considered by users already experienced with holmium laser enucleation of the prostate.

Purpose of Review: An increasing volume of research has been directed at the prevention of prostate cancer. This review proposes to summarize the large trials, novel approaches and molecular mechanisms of effect published in 2004 and 2005., Recent Findings: The impact of the Prostate Cancer Prevention Trial continues and subsequent articles have addressed the increase of high-grade prostate cancers detected in the finasteride arm of the trial, as well as the potential costs and benefits of extrapolating the findings to a public health campaign. Studies of risk have been published warning of excessive vitamin E and cyclooxygenase-2 inhibitor use in chemoprevention. Growing evidence supports the concept of chemopreventative agent combinations and further data on the roles of selenium, lycopene, soy, green tea, anti-inflammatories and statins in prostate-cancer prevention are presented., Summary: Level one evidence exists for the preventative effects of finasteride in prostate cancer. The evidence for other agents is less conclusive but a number of large-scale, appropriately designed trials will hopefully address some of the relevant issues in prostate-cancer prevention over the next decade.