Brachytherapy for prostate cancer: effective, but...?
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Brachytherapy↗
Biomedical subjects
J C Nickel
Publications and source records attributed to J C Nickel.
Strain rate dependent orthotropic properties of pristine and impulsively loaded porcine temporomandibular joint disk.
The purpose of this study was to characterize the tensile stress-strain behavior of the porcine temporomandibular joint (TMJ) disk with respect to collagen orientation and strain rate dependency. The apparent elastic modulus, ultimate tensile strength, and strain at maximum stress were measured at three elongation rates (0.5, 50, and 500 mm/min) for dumbbell-shaped samples oriented along either anteroposterior or mediolateral axes of the disks. In order to study the effects of impact-induced fissuring on the mechanical behavior, the same properties were measured along each orientation at an elongation rate of 500 mm/min for disks subjected to impulsive loads of 0.5 N. s. The results suggested a strongly orthotropic nature to the healthy pristine disk. The values for the apparent modulus and ultimate strength were 10-fold higher along the anteroposterior axis (p < or = 0.01), which represented the primary orientation of the collagen fibers. Strain rate dependency was evident for loading along the anteroposterior axis but not along the mediolateral axis. No significant differences in any property were noted between pristine and impulsively loaded disks for either orientation (p > 0.05). The results demonstrated the importance of choosing an orthotropic model for the TMJ disk to conduct finite element modeling, to develop failure criteria, and to construct tissue-engineered replacements. Impact-induced fissuring requires further study to determine if the TMJ disk is orthotropic with respect to fatigue.
Animals↗
Human interleukin-1 beta and interleukin-1 receptor antagonist secretion and velocity of tooth movement.
The cytokines interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1RA) probably play a part in orthodontic tooth movement. Here, the force magnitudes and the area of force application in the compressed periodontal ligament (PDL) were controlled and the velocity of tooth movement correlated with concentrations of IL-1 beta and IL-1RA in the gingival crevicular fluid (GCF). Seven individuals undergoing orthodontic treatment involving maxillary first premolar extractions and distal movement (bodily retraction) of the maxillary canines participated in the 84-day study. For each participant, continuous retraction forces were applied so that they received equivalent PDL stresses of 13 kPa for one canine and 4 kPa for the other. GCF cytokine concentrations from experimental and control teeth were expressed relative to total protein in the GCF and compared using an 'Activity Index' (AI)=Experimental (IL-1 beta/IL-1RA)/Control (IL-1 beta/IL-1RA). The results showed that the velocity of tooth movement in an individual was related to their AI. The correlation between AI and tooth movement was stronger from the distal (R(d)=0.78) than from the mesial (R(m)=0.65) of retracted teeth. The results demonstrate that equivalent force systems produce individual differences in cytokine production, which correlate with interindividual differences in the velocity of canine retraction.
Cuspid↗
The effect of disc thickness and trauma on disc surface friction in the porcine temporomandibular joint.
The pathomechanics of osteoarthritis in the human temporomandibular joint (TMJ) are unknown. Compromised lubrication is a potential factor, but, lubrication within even the normal TMJ is not understood completely. Weeping lubrication is a concept that may be applicable to the TMJ. A characteristic of weeping lubrication is a slow increase in friction during static loading. The rate of increase in friction is related to the rate of lateral movement of synovial fluid away from the loading area. The TMJ disc is expected to be the main source of TMJ lubrication. This study tested two variables, disc thickness and magnitude of trauma to the disc, as factors that can affect the rate of flow of synovial fluid and thus alter lubrication of the disc surfaces. To test these variables, TMJ disc surface friction was measured before and after an impulse load. Before the impulse load, all discs demonstrated a gradual increase in friction during light static loading. The rate of increase in friction was inversely related to the disc thickness (R(2)=0.75). After an impulse load of known magnitude and peak force, disc surface friction was higher. The magnitude of this surface friction was correlated with the magnitude of the impulsive blow (R(2)=0.89) and the area of surface damage (R(2)=0.85). Disc thickness was a significant factor in determining the minimal impulse needed to produce higher surface friction (R(2)=0.99). These results confirm that disc thickness and trauma to the disc affect surface friction in the TMJ, and therefore may be important factors in compromised lubrication and the development of osteoarthritis.
Animals↗
Impact of medical therapy on transurethral resection of the prostate: a decade of change.
OBJECTIVES: To assess whether medical therapy has delayed the need for eventual transurethral prostatectomy (TURP), causing a shift in the population characteristics of men undergoing TURP (ie, older, more comorbidities, more advanced disease), resulting in more complications and poorer outcomes. The introduction of medical therapy for symptomatic benign prostatic hyperplasia (BPH) during the past decade may have changed the indications for TURP. METHODS: All patients who underwent TURP for symptomatic BPH at our institution in 1988 (before general introduction of medical therapy for BPH) and 1998 (medical therapy the primary initial therapy for BPH) were reviewed. We compared the two groups with respect to the total number of TURPs, indications for surgery, patient age, health status, weight of resected tissue, and preoperative and postoperative complications. RESULTS: Despite a 16% increase in men at risk of BPH-related events, a 60% decrease in the total number of TURPs performed for symptomatic BPH occurred in 1998 (n = 64) compared with 10 years earlier (n = 157). No significant difference was found in age between the two groups, and no increase in comorbid status was observed. Previous medical management had failed in 36% of men who required TURP in 1998. A significantly higher percentage of patients presented in acute urinary retention (55%) and upper tract obstructive uropathy (12.5%) in 1998 compared with 1988 (23% acute urinary retention and 1.3% obstructive uropathy). Patients in 1998 were healthier, underwent smaller resections, had their catheters removed earlier, and were discharged home earlier. Although they were more likely to be discharged home with a catheter in situ, no significant difference was observed in the incidence of postoperative complications. CONCLUSIONS: There has been a dramatic decrease in the number of TURPs performed for symptomatic BPH at our institution since the advent of medical therapy. The proportion of TURP patients presenting with urinary retention and hydronephrosis increased, but the average age, medical comorbidities, operative parameters, and postoperative complications have not significantly changed.
Age Factors↗
Safety and efficacy of up to 900 mg/day polysulfate sodium (elmiron) in patients with interstitial cystitis.
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Anti-Inflammatory Agents, Non-Steroidal↗
The information required by patients with early-stage prostate cancer in choosing their treatment.
OBJECTIVE: To determine the information that men diagnosed with early-stage prostate cancer think is necessary to choose their treatment (surgery, radiotherapy or 'watchful waiting'). PATIENTS AND METHODS: All men diagnosed with early-stage prostate cancer in a regional urology practice in an 18-month period were surveyed. Respondents considered the treatment decision for a specific hypothetical case and judged whether each of 59 specific information items would be 'necessary' to know to make the treatment decision. Respondents provided basic demographic information (age, education and marital status). RESULTS: Of 89 patients, 71 (80%) responded; the mean (SD, range) number of items that individual respondents identified as necessary was 32 (12, 9-58). Each item was considered necessary by 54 (18, 20-93)% of respondents. Of the 59 items, only five were necessary to > or = 80% of respondents; 23 were necessary to > or = 67% of respondents and five were not necessary to > or = 67% of respondents. Patients were divided about the remaining 31 items. There were no strong correlations (none accounted for > 20% of the variance) between the responses and demographic characteristics. CONCLUSIONS: There appears to be large variation among patients with early-stage prostate cancer in the number of information items deemed necessary to make a treatment decision, and little agreement on the need for most individual items. Demographic characteristics were not useful as predictors of the information needs of each patient. The process of informing patients with early-stage prostate cancer (and their decision aids) needs to be flexible and able to accommodate a wide range of patients' information needs.
Aged↗
Consensus development of a histopathological classification system for chronic prostatic inflammation.
OBJECTIVE: To develop a standardized histopathological classification system for chronic prostatitis (standardized description of prostatic inflammatory infiltrates) based on a literature review, extensive prospective evaluations in two recognized prostatitis research centres and widespread consensus of international urological centres identified as having major expertise or interest in chronic prostatitis. METHODS: Relevant articles for review were identified by a Medline search undertaken by the Cochrane Review Group in Prostate Diseases and Urologic Malignancies, and cross-checking bibliographies of retrieved studies, reviews, book chapters and abstracts of the American Urological Association and International Prostatitis Collaborative Network Annual Meetings. Initial drafts were based on classification systems independently developed by the Prostatitis Research Centers at Queen's University in Canada and University of Washington in the USA. A collaborative draft was distributed to 20 urological/pathological clinical centres who participated in the North American Chronic Prostatitis Collaborative Research Network and First International Prostatitis Collaborative Network. A consensus classification system was then distributed to the participating panel for acceptance. RESULTS: The literature review identified a reasonably consistent description of inflammatory infiltrate locations and patterns that were further incorporated into the draft based on the Queen's University and University of Washington proposals. Eighteen (90%) of the identified Prostatitis Centers participated in the revision of the draft and the final consensus process. The final consensus document classifies prostatic inflammation according to its extent and grade/severity in each tissue compartment (location). Conclusion The consensus of the expert panel was that this classification system can be used in the evaluation of prostatic inflammation in prostate biopsies, transurethral resected prostate chips or prostatectomy specimens. A standardized accepted framework to describe histopathological prostate inflammation will prove useful in evaluating prostate disease.
Chronic Disease↗
Absorption of alkalized intravesical lidocaine in normal and inflamed bladders: a simple method for improving bladder anesthesia.
PURPOSE: Pharmacokinetic studies have shown that intravesical lidocaine is not sufficiently absorbed by human bladders to achieve significant serum levels and it only provides a superficial local anesthetic effect. We investigated the pharmacokinetics of alkalized intravesical lidocaine in healthy volunteers and patients with interstitial cystitis to determine a safe dose of buffered lidocaine, the effect of interstitial cystitis on lidocaine uptake and the acute local anesthetic effect on bladder pain in interstitial cystitis. MATERIALS AND METHODS: An initial dose finding study was done in 12 healthy volunteers using 4, 5 and 6 mg./kg. 5% lidocaine buffered with 8.4% sodium bicarbonate. Serial lidocaine levels were measured for 3 hours. Serum measurement was repeated in 12 patients with interstitial cystitis using 5 mg/kg. 5% lidocaine with sodium bicarbonate daily for 2 days. Patients rated pain before and during treatment. RESULTS: Healthy volunteers and patients with interstitial cystitis had similar lidocaine absorption profiles with a peak of 1.06 microg/ml. (range 0.66 to 1.71) and 1.3 (range 0.2 to 2.0) at about 30 minutes. Mean pain score in the interstitial cystitis group decreased from a baseline of 6.0 to 1.8 on day 1 and 0.6 on day 2. There were complaints of urethral discomfort after voiding the buffered lidocaine in each group. CONCLUSIONS: Alkalization provides safe and predictable lidocaine absorption into the bladder, as indicated by therapeutic systemic levels in healthy and inflamed bladders. Furthermore, the decrease in acute pain scores in the interstitial cystitis group indicated a concentration of local anesthetic within the bladder wall that was sufficient to block the sensory neurons within the submucosal plexus.
Absorption↗
Prevalence of prostatitis-like symptoms in a population based study using the National Institutes of Health chronic prostatitis symptom index.
PURPOSE: The National Institutes of Health (NIH) chronic prostatitis symptom index was used to determine the prevalence of prostatitis-like symptoms among men (age 20 to 74 years) at risk in a community based study. MATERIALS AND METHODS: The study was a cross-sectional postal survey of men age 20 to 74 years in Lennox and Addington counties, which included a large rural area, 1 major town and a suburban area with a stable population of men representative of Canadian demographics. The questionnaire collected information on 2 domains of chronic prostatitis identified in the NIH chronic prostatitis symptom index, including pain (location, severity and frequency), voiding function (irritative, obstructive), demographics, quality of life, general health and health seeking behavior. The self-reported pain score was used to identify prostatitis-like symptoms in the most discriminating domain. Based on analysis of the index final validation study comparing patients with prostatitis to normal controls and those with benign prostatic hyperplasia, the 2 questions most specific for prostatitis, including perineal and/or ejaculatory pain/discomfort, and a total pain score (0 to 21) 4 or greater were used to identify men with significant prostatitis-like symptoms. RESULTS: A total of 2,987 eligible men received the survey, and it was completed by 868 (29%). Of the men 84 (9.7%) were identified as having chronic prostatitis-like symptoms (mean NIH chronic prostatitis symptom index pain score 9.1 +/- 0.3). The average age of the prostatitis population was 50 years compared with 52 years for men without prostatitis-like symptoms. Prevalence was 11.5% in men younger than 50 years and 8.5% in men 50 years or older. Of the sampled population 57 (6.6%) men had prostatitis-like symptoms and an index pain score 8 or greater (moderate to severe). The index voiding score (0 to 10) was 4.1 +/- 0.5 in men younger than 50 years compared with 1.5 +/- 0.1 for normal controls, and 4.7 +/- 0.4 in those 50 years or older compared with 1.9 +/- 0.1 for normal controls. Of the prostatitis group 60% sought medical help for their symptoms. CONCLUSIONS: In our opinion this community based study using the new prostatitis symptom index confirms that chronic prostatitis-like symptoms are common.
Adult↗
Predictors of patient response to antibiotic therapy for the chronic prostatitis/chronic pelvic pain syndrome: a prospective multicenter clinical trial.
PURPOSE: To our knowledge antibiotics are the most popular choice of therapy for all categories of the chronic prostatitis/chronic pelvic pain syndrome. We determine if culture, leukocyte and/or antibody status of prostate specific specimens predicts patient response to antibiotic therapy. MATERIALS AND METHODS: Patients clinically diagnosed with the chronic prostatitis/chronic pelvic pain syndrome according to the National Institutes of Health (NIH) definition had a lower urinary tract evaluation that included standard microscopy and culture of prostate specific specimens, and determination of the ratio of voided bladder 3 and voided bladder 2 antibody levels against a panel of identified prostate pathogens (enzyme linked immunosorbent assay methodology). Symptom evaluation consisted of the NIH chronic prostatitis symptom index (derived) pain scale 0 to 21, symptom severity index scale 0 to 100, symptom frequency questionnaire scale 0 to 50 and quality of life scale 0 to 6. Patients were stratified according to microscopy, culture and immune status, were treated with 12 weeks of ofloxacin, and were assessed at 4, 12 and 24 weeks with symptom scores as well as global assessments. RESULTS: Based on leukocyte and culture results, 102 evaluable patients were stratified into categories II (14%), IIIA (48%) and IIIB (38%) of the chronic prostatitis/chronic pelvic pain syndrome. Of the cases 23% were categorized as antibody positive and 77% as antibody negative. Average age was 42 +/- 10 years and 92% of patients were white. Of the patients 57% believed that they had moderate to marked improvement. All categories of the chronic prostatitis/chronic pelvic pain syndrome and patients in whom antibody was positive or negative had significant improvement in the NIH chronic prostatitis symptom index, symptom severity index, symptom frequency questionnaire and quality of life scores compared with baseline (p <0.001). There was no significant difference in patient response to the stratification based on culture, leukocyte, that is categories II, IIIA and IIIB had same beneficial response, or antibody status. CONCLUSIONS: Culture, leukocyte and antibody status of prostate specific specimens does not predict antibiotic response in patients with the chronic prostatitis/chronic pelvic pain syndrome. The perceived beneficial effect of antibiotics needs to be evaluated in a randomized placebo controlled trial.
Anti-Infective Agents↗
The management of acute pyelonephritis in adults.
Acute pyelonephritis should be classified clinically at the time of presentation into either uncomplicated or complicated categories. The diagnostic workup includes history, physical examination, urinalysis (including a Gram stain), and urine culture. Patients with suspected complicated pyelonephritis require the standard assessment plus blood cultures and urinary tract imaging, preferably a computed tomography (CT) scan. Patients with moderate, uncomplicated pyelonephritis can be managed as outpatients with either a fluoroquinolone (7-14 days) or trimethoprim/sulfamethoxazole (at least 14 days). Patients with severe, uncomplicated pyelonephritis can be considered for short-term hospitalization and initial administration of intravenous antibiotics. Therapy for patients with complicated pyelonephritis should include initial hospitalization, supportive therapies, administration of wide spectrum intravenous antibiotic therapy, and relief of aggravating conditions. Such maneuvers could consist of simple bladder catheterization, percutaneous nephrostomy drainage, or definitive surgery. Patients with complicated pyelonephritis require longer duration of culture-specific antibiotic dosing, careful monitoring, long-term follow-up, and possible definitive management of their underlying condition.
Acute Disease↗
Benign mixed epithelial stromal tumor of the kidney of possible müllerian origin.
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Female↗
Rat model of experimentally induced abacterial prostatitis.
BACKGROUND: An experimental model in rats was developed to investigate the significance of mucosal integrity in abacterial prostatitis. METHODS: Ethanol was instilled into the ventral prostates of male rats to reduce mucosal integrity; dinitrobenzenesulfonic acid (DNBS) was added as an irritant to induce inflammation. Controls received no treatment, ethanol only, DNBS only, or a suspension of bacteria. After various time points, rats were sacrificed, and their prostates were assayed for gross morphology, histological appearance, and cytokine levels. RESULTS: Prostates subjected to ethanol plus DNBS showed significant inflammation, most notably after 12, 24, and 48 hr. Inflammation judged by gross and histological observations and interleukin-1beta levels correlated well at these times. Rats given only ethanol, DNBS, or no treatment, acting as negative controls, displayed little or no inflammation; rats given a bacterial suspension, acting as positive controls, showed inflammation consistent with past studies. Cytokine assays revealed raised interleukin-1beta levels in this model, while tumor necrosis factor-alpha remained at a basal level. CONCLUSIONS: The loss of an intact mucosal surface in the prostate resulted in inflammation caused by an irritant. Interleukin-1beta appears to play a role in this inflammation, while tumor necrosis factor-alpha does not.
Animals↗
Pentosan polysulfate therapy for chronic nonbacterial prostatitis (chronic pelvic pain syndrome category IIIA): a prospective multicenter clinical trial.
OBJECTIVES: Chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) has clinical and perhaps etiologic characteristics similar to interstitial cystitis. Pentosan polysulfate sodium (PPS), an oral medication indicated for the treatment of interstitial cystitis, has shown moderate benefit in reducing chronic pelvic pain and voiding symptoms in patients with interstitial cystitis. We undertook a prospective open-label, multicenter Phase II pilot study to examine the potential efficacy of PPS in the treatment of CPPS in men, using outcome tools validated for CPPS in men. METHODS: Patients with a diagnosis consistent with National Institutes of Health (NIH) CPPS category IIIA (inflammatory) were treated with PPS, 100 mg three times daily, for 6 months. The evaluation at baseline, 3 months, and 6 months consisted of the Symptom Severity Index, a Symptom Frequency Questionnaire, the NIH-Chronic Prostatitis Symptom Pain Index (NIH-CPSI), a quality-of-life assessment, and a subjective global assessment. RESULTS: Thirty-two patients (mean age 45.5 +/- 11 years; duration of symptoms 9.2 +/- 12 years) were enrolled in five centers; 28 patients were available for evaluation. Seven patients experienced drug-related side effects, including hair loss (n = 2), headache (n = 2), mild nausea (n = 1), mild weight gain (n = 1), and skin flushing (n = 1). The decrease in frequency (Symptom Frequency Questionnaire 28.1 to 17.9), severity (Symptom Severity Index 53.6 to 36.3), and combined location/frequency/severity of pain (NIH-CPSI pain 14.5 to 9.2) symptom scores at 6 months compared with baseline was significant. The decrease was associated with a significant improvement in patients' quality of life (quality-of-life assessment 5.3 to 3.8). Forty-three percent of the patients had a greater than 50% improvement in the Symptom Frequency Questionnaire, Symptom Severity Index, and NIH-CPSI (rated as clinically significant improvement). At 6 months, mild, moderate, and marked improvement was noted (subjective global assessment) by 33%, 19%, and 15% of the patients, respectively. CONCLUSIONS: PPS is well tolerated and appears to have efficacy in reducing the severity and frequency of general symptoms, reducing specific pain symptoms, and improving the quality of life in many male patients with CPPS. The results of this study justify the initiation of a randomized controlled trial comparing the safety and efficacy of PPS to placebo.
Adult↗
Prostatitis: the last frontier.
Prostatitis, the neglected third disease (after benign prostatic hypertrophy and prostate cancer) is the last frontier of prostate disease. Innovative new research and clinical initiatives have revived urologists' interest in this difficult and frustrating disease. New funding initiatives, industry interest and powerful patient lobby groups have put this long-neglected syndrome back on the urologic agenda. Presented here is an inventory of what is and is not known about prostatitis. It is based on a review of the literature, undisputed facts, solid hypotheses, and common sense. Also offered is a series of personal challenges to the urologic community. As we enter the twenty-first century we must develop a rational management strategy for patients who present with symptoms of prostatitis.
Humans↗
Human tooth movement in response to continuous stress of low magnitude.
Conventional orthodontic therapy often uses force magnitudes in excess of 100 g to retract canine teeth. Typically, this results in a lag phase of approximately 21 days before tooth movement occurs. The current project was undertaken to demonstrate that by using lower force magnitudes, tooth translation can start without a lag phase and can occur at velocities that are clinically significant. Seven subjects participated in the 84-day study. A continuous retraction force averaging 18 g was applied to 1 of the maxillary canines, whereas a continuous retraction force averaging 60 g was applied to the other. The magnitude was adjusted for each canine to produce equivalent compressive stresses between subjects. Estimated average compressive stress on the distal aspect of the canine teeth was 4 kPa or 13 kPa. The moment-to-force ratios were between 9 and 13 mm. Tooth movement in 3 linear and 3 rotational dimensions was measured with a 3-axis measuring microscope and a series of dental casts made at 1- to 14-day intervals. The results showed a statistical difference in the velocity of distal movement of the canines produced by the 2 stresses (P =.02). The lag phase was eliminated and average velocities were 0.87 and 1.27 mm/month for 18 and 60 g of average retraction force. Interindividual velocities varied as much as 3 to 1 for equivalent stress conditions. It was concluded that effective tooth movement can be produced with lower forces and that because loading conditions were controlled, cell biology must account for the variability in tooth velocities measured in these subjects.
Adolescent↗
Prostatitis: lessons from the 20th century.
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Forecasting↗