Prospects and limitations of treatment with botulinum neurotoxin type A for patients with refractory idiopathic detrusor overactivity.

In this review we summarize the recent innovation of botulinum-A neurotoxin (BoNT-A) injections in the bladder as a potential new treatment option for idiopathic detrusor overactivity, refractory to conventional anticholinergic medication. BoNT-A is produced by Clostridium botulinum and consists of a 150-kDa neurotoxic protein that has the ability to cleave proteins within the nerve terminal. BoNT-A is thereby able to prevent acetylcholine release at the presynaptic membrane, resulting in a chemodenervation of the detrusor muscle after intravesical injection; this can reduce symptoms in patients with refractory idiopathic detrusor overactivity. BoNT-A intradetrusor injections might be an alternative to invasive surgery for patients in whom conservative measures and anticholinergic treatment have failed. Clinical studies with different dosages and injection protocols show success rates of 60-96% for neurogenic and non-neurogenic detrusor overactivity, with wide variations in the duration of response. The drug is still under development for the indication of idiopathic detrusor overactivity, and is under ongoing investigation for long-term efficacy and safety.

[Extraperitoneal radical prostatectomy Da Vinci]. / Prostatectomía radical extraperitoneal Da Vinci.

OBJECTIVE: To report the outcomes of 100 robotically assisted laparoscopic radical prostatectomies (RALPs), a minimally invasive alternative for treating prostate cancer. PATIENTS AND METHODS: In all patients was used RALP with an extraperitoneal approach assisted by the da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA, USA). Prospective data collection included quality-of-life questionnaires, basic demographics (height, weight and body mass index), prostate specific antigen (PSA) levels, clinical stage and Gleason grade. Variables assessed during RALP were operative duration, estimated blood loss (EBL) and complications, and after RALP were hospital stay, catheter time, pathology, PSA level, return of continence and potency. RESULTS: The mean (range) duration of RALP was 180 (140-295) min; all procedures were successful, with no intraoperative transfusions or deaths. The mean EBL was 300 mL (40-1100); 97% of patients were discharged home on the first day after RALP with a mean haematocrit of 36%. The mean duration of catheterization was 7 (5-21) days. The positive margin rate was 14% for all patients. The overall biochemical recurrence free (PSA level < 0.1 ng/mL) survival was 95% at mean follow-up of 9.7 months. There was complete continence at 6 months in 95% of patients. At 1 year 78% of patients were potent (with or without the use of oral medications), 15% were not yet able to sustain erections capable of intercourse, and another 7% still required injection therapy. CONCLUSION: RALP is a safe, feasible and minimally invasive alternative for treating prostate cancer. Our initial experience with the procedure shows promising short-term outcomes.

Prostatectomía radical extraperitoneal Da Vinci / Extraperitoneal radical prostatectomy Da Vinci

Objetivo. Informar de la evolución de 100 prostatectomías radicales laparoscópicas asistidas por robot (RALPs), una alternativa minimamente invasiva para el tratamiento del cáncer de próstata. Pacientes y métodos. Se realizó un abordaje extraperitoneal asistidos por el sistema quirúrgico robótico Da Vinci. Los datos prospectivos incluyeron cuestionarios de calidad de vida, demografía básica (peso, altura e índice de masa corporal), niveles de PSA, estadio clínico y suma de Gleason. Las variables intraoperatorias evaluadas fueron duración de la cirugía, pérdida sanguínea estimada (EBL) y complicaciones. Post-operatoriamente se evaluaron los días de estancia en el hospital, días con catéter uretral, histopatología, niveles de PSA, recuperación de la continencia y la potencia. Resultados. La duración media de la RALP fue de 180 minutos (rango 140-295); todos los procedimientos tuvieron éxito y no se registraron transfusiones sanguíneas ni muertes relacionadas con la cirugía. La EBL media fue 300 cc ( 40 -1100); 97 % de los pacientes fueron dados de alta el primer dia de post-operatorio con 36 % de hematocrito. La duración media del cateterismo uretral fue 7 dias ( 5-21). La tasa de margenes positivos fue del 14 %. La continencia a los 6 meses fue del 95 %. La supervivencia libre de recidiva bioquímica fue del 95 % al año. Al año 78 % de los pacientes eran potentes( con o sin ayuda farmacológica), 15 % no eran capaces de mantener la erección para penetrar y 7 % necesitaban aún inyecciones intracavernosas. Conclusión: La prostatectomía radical laparoscópica asistida por robot se caracteriza por un control máximo en cuanto a la resección de tejido, una pérdida de sangre mínima y unos resultados funcionales muy buenos

Objetive. To report the outcomes of 100 robotically assisted laparoscopic radical prostatectomies (RALPs), a minimally invasive alternative for treating prostate cancer. Patients and methods. In all patients was used RALP with an extraperitoneal approach assisted by the da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA, USA). Prospective data collection included quality-of-life questionnaires, basic demographics (height, weight and body mass index), prostate specific antigen (PSA) levels, clinical stage and Gleason grade. Variables assessed during RALP were operative duration, estimated blood loss (EBL) and complications, and after RALP were hospital stay, catheter time, pathology, PSA level, return of continence and potency. Results. The mean (range) duration of RALP was 180 (140-295) min; all procedures were successful, with no intraoperative transfusions or deaths. The mean EBL was 300 mL (40 – 1100); 97% of patients were discharged home on the first day after RALP with a mean haematocrit of 36%. The mean duration of catheterization was 7 (5-21) days. The positive margin rate was 14% for all patients. The overall biochemical recurrence free (PSA level <0.1 ng/mL) survival was 95% at mean follow-up of 9.7 months. There was complete continence at 6 months in 95% of patients. At 1 year 78% of patients were potent (with or without the use of oral medications), 15% were not yet able to sustain erections capable of intercourse, and another 7% still required injection therapy. Conclusion. RALP is a safe, feasible and minimally invasive alternative for treating prostate cancer. Our initial experience with the procedure shows promising short-term outcomes

IGFII and MIB1 immunohistochemistry is helpful for the differentiation of benign from malignant adrenocortical tumours.

AIMS: The differentiation of adrenocortical carcinomas from adenomas may be difficult based on morphology alone. Differential expression of insulin-like growth factor (IGF) II and cyclin-dependent kinase (CDK) 4 has recently been described in these tumours. The aim of this study was to investigate the diagnostic usefulness of these markers immunohistochemically. METHODS AND RESULTS: We examined 22 benign and 17 malignant adrenocortical tumours and compared IGFII and CDK4 expression with known immunohistochemical as well as morphological criteria of malignancy. Thirteen of 17 carcinomas showed immunohistochemical reactivity for IGFII, whereas all adenomas but one were negative. Intense CDK4 expression was detected in 11 of 17 carcinomas but was present in only three of 22 adenomas. The MIB1 index was >5% in 14 of 16 carcinomas and was <5% in all adenomas but one. The combination of IGFII immunohistochemistry with MIB1 index led to high sensitivity and specificity in detecting adrenocortical carcinomas. CONCLUSIONS: IGFII and MIB1 are helpful immunohistochemical markers to predict malignancy in adrenocortical neoplasms. These markers can be used in addition to clinical, gross and morphological features to establish a diagnosis in difficult cases.

Experience with 100 cases treated with botulinum-A toxin injections in the detrusor muscle for idiopathic overactive bladder syndrome refractory to anticholinergics.

PURPOSE: In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. MATERIALS AND METHODS: A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. RESULTS: Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance. Mean efficacy duration +/- SD was at least approximately 6 +/- 2 months and then symptoms began to increase. CONCLUSIONS: Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments.

Expression of smoothelin in the normal and the overactive human bladder.

PURPOSE: We established the expression pattern of smoothelin, a marker protein for contractile smooth muscle cells, in the human detrusor and investigated its possible impact on bladder overactivity. MATERIALS AND METHODS: Detrusor samples of 13 overactive bladders (sensory urge and detrusor instability) were obtained before botulinum toxin injection and compared to those of 8 normally contractile, nonobstructed bladders obtained during radical cystectomy. Smoothelin mRNA expression patterns were investigated by Northern blot and variant specific reverse transcriptase-polymerase chain reaction as well as by quantitative reverse transcriptase-polymerase chain reaction on laser capture, microdissected smooth muscle. At the protein level smoothelin was investigated by standard and quantitative immunohistochemistry. RESULTS: The bladder muscularis expressed vascular and visceral smoothelin isoforms, and 2 of the known splice variants. In the smooth muscle of patients with detrusor instability and sensory urge a significant 2.4 and 2.2-fold increase, respectively, in smoothelin variant 1 mRNA was observed in comparison to that of normal controls. Analyses at the smoothelin protein level confirmed significant up-regulation in these bladder dysfunctions by a factor of 2.3 and 1.8, respectively. No significant difference in smoothelin expression was observed between detrusor instability and sensory urge. CONCLUSIONS: Increased expression of smoothelin in patients with detrusor instability and sensory urge implies that the etiology of these dysfunctions includes changes in myogenic parameters. In addition, our data support the new classification of the International Continence Society for overactive bladder proposing that sensory urge and detrusor instability represent a single clinical entity.

Neurovascular bundle block as predictor of postoperative erectile function after radical prostatectomy.

We assessed audiovisually induced erections after nerve block of the neurovascular bundle during prostate biopsy. We evaluated neurovascular bundle nerve block to mimic non-nerve-sparing radical prostatectomy in an experimental setup. Patients undergoing a transrectal ultrasound-guided prostate biopsy were randomized to bilateral injection of 5 ml ropivacaine hydrochloride 0.75% or NaCl 0.9% into the neurovascular bundle. The patients completed the International Index of Erectile Function 5-item questionnaire (IIEF-5) questionnaire, and a detailed patient history was obtained. A routine prostate biopsy was performed. Thereafter, patients were exposed to 60 min of audiovisual stimulation. Erections were recorded using a Rigiscan-Plus device. A total of 11 patients were randomized. Five patients received NaCl (group 1) and six patients ropivacaine (group 2). Patient characteristics were comparable in terms of age (group 1: 59.8 y; group 2: 61.8 y), mean PSA (4.1 vs 4.7 ng/ml), mean IIEF-5 score (20.5 vs 22) and risk factors for erectile dysfunction, respectively. Patients of group 1 showed significantly stronger and longer erections after audiovisual stimulation than patients in group 2. Patients with bilateral infiltration of saline solution to the neurovascular bundle showed significantly stronger erections than patients receiving local anesthesia of the neurovascular bundle. Thus, this experiment might serve as a model to assess postoperative erectile function after a unilateral nerve-sparing radical prostatectomy.

Nocturnal penile tumescence and rigidity (NPTR) findings in spinal cord injured men with erectile dysfunction.

This prospective study aimed at determining whether nocturnal penile tumescence and rigidity (NPTR) findings correlate to the neurologic disorders in spinal cord injured (SCI) patients suffering from erectile dysfunction (ED). A total of 25 acute SCI male patients with post-traumatic ED underwent neurological, electrophysiological and urodynamic examinations, respectively, as well as NPTR recordings. The mean value for rigidity (R), tumescence (T) and duration (D) during NTPR tests were 83.3%, 3.3 cm, 6.4 min in patients with a complete lesion above the sacral (S2-S4) spinal cord (n=10), 46.1%, 1.6 cm, 5.5 min in patients with a complete lesion involving the sacral metameres (n=5) and 89.8%, 3.8 cm, 29 min in patients with an incomplete suprasacral lesion (n=7). The differences among these groups were statistically significant (P<0.05). Patients with lesions involving both sacral and thoracolumbar spinal cord showed no erections (n=3). We found four NTPR patterns: (1) normal R and T, short D; (2) weak R and T, short D; (3) normal R, T and D; and (4) no erections, which can be assigned to different levels and completeness of spinal cord lesions. Nocturnal erections of normal quality need preservation of thoracolumbar and sacral neuronal control as well as partially intact connections of the spinal erection centres with brain areas responsible for sexual arousal.

Autonomic dysreflexia in response to pudendal nerve stimulation.

STUDY DESIGN: Pudendal nerve stimulation in complete spinal cord injury (SCI). OBJECTIVE: To evaluate the influence of pudendal nerve stimulation on the cardiovascular system in SCI patients in order to assess the underlying neuronal mechanism and the potential risk during stimulation. SETTING: Swiss Paraplegic Center, and University Hospital, Zurich. METHODS: A total of 22 male patients with a complete SCI were divided into two groups according to the level of lesion: group A (C6-T6, n=15) and group B (T7-L2, n=7). A total of 66 stimulations using biphasic rectangular impulses (0.2 ms, 10 Hz) with intensities up to 100 mA were applied to the dorsal penile nerve. Of these, 15 stimulations in five patients were repeated after intravenous application of 7 mg of phentolamine. Heart rate (HR) and blood pressure (BP) were recorded by a Finapres cuff applied to the right index finger. RESULTS: Significant increased diastolic and systolic BP accompanied by significant decreased HR suggested the occurrence of autonomic dysreflexia (AD) during pudendal nerve stimulation. These cardiovascular changes corresponded with the subjective sensation of AD symptoms in patients of group A. Intravenous phentolamine lowered the resting BP and prevented severe hypertension during stimulation. Patients in group B presented with mild HR and BP changes in response to pudendal nerve stimulation and reported no AD symptoms. CONCLUSION: Our results show a considerable effect of electrical pudendal nerve stimulation on HR and BP in patients with high SCI. This may indicate that sacral somatic afferent fibers of the pudendal nerve are involved in the neuronal mechanism of AD in SCI patients with high neurological level. Intravenous phentolamine enables pudendal nerve stimulation without the risk of severe hypertension.

Clinical value of combined electrophysiological and urodynamic recordings to assess sexual disorders in spinal cord injured men.

AIMS: To assess the significance of combined neurophysiological and neurourological examinations for diagnosis of neurogenic male sexual dysfunction. METHODS: This is a prospective study of 32 spinal cord injured men. Each underwent clinical and neurophysiological examinations (sympathetic skin responses (SSR), pudendal somato-sensory evoked potentials (P-SSEP), bulbocavernosus reflex (BCR)) and neuro-urological measurements (urodynamic examination (UE), reflex erections (RE), psychogenic erections (PE) and nocturnal penile tumescence recordings (NPTR)). RESULTS: Erectile dysfunction due to impairment of RE was associated with loss of BCR and detrusor areflexia (P > 0.001), whereas that due to impairment of PE was associated with loss of perineal SSR (P < 0.001). P-SSEP corresponded in 94% with impairment of penile sensibility and duration of erections in NPTR. The NPTRs were less related to functional sexual impairment. NPTRs in complete and incomplete suprasacral (level > T10) spinal lesion showed sufficient erections despite strongly disturbed PE. NPTRs in lumbosacral lesion revealed significant reduction in or absent erections and underestimated the presence of well excitable PE. CONCLUSIONS: Combined neurophysiologic and neurourologic testing provides highly relevant diagnostic informations about sexual dysfunction in men with spinal cord injury. Loss of the BCR and detrusor areflexia imply loss of somatic and parasympathetic reflex activity and correlate with loss of RE. Loss of PE correlates with loss of perineal SSR (sympathetic denervation).

[Urinary incontinence in the man--pathophysiology and diagnosis]. / Harninkontinenz beim Mann--Pathophysiologie und Diagnostik.

About 7-8% of men experience unvoluntary urinary leak. Incidence in patients older than 60 years is 2-3 fold increased. Urge incontinence is the mostly present, less frequent are overflow-incontinence/chronic retention and urinary stress incontinence. In men, prostate and bladder dysfunction as well as neurologic diseases are responsible for urinary incontinence. The baseline diagnostics include micturition protocols, the urologic clinical examination, residual urine determination and laboratory analyses of urine and blood. Extended diagnostics proceed to morphological and infectious etiologies and base on urodynamic evaluation.

Electrophysiological assessment of sensations arising from the bladder: are there objective criteria for subjective perceptions?

PURPOSE: Initial bladder filling sensation, first and strong desire to void are subjective perceptions that occur periodically during the urine storage mode of bladder function, representing sensory input from the lower urinary tract. To our knowledge methods for evaluating sensory bladder function are not available. We studied a simple electrophysiological procedure for the objective assessment of bladder sensations using sympathetic skin responses and surface pelvic floor electromyography. MATERIALS AND METHODS: Informed consent was provided by 8 healthy male subjects, who were administered 20 mg. furosemide and 1 l. fluid to drink. Palmar and plantar sympathetic skin responses, and surface pelvic floor electromyogram were continuously recorded during bladder filling, voluntary pelvic floor contraction and voiding. RESULTS: First desire to void evoked simultaneous sympathetic skin responses and pelvic floor contractions. This pattern appeared periodically with the desire to void sensation as well as with strong desire to void at maximum bladder capacity and it correlated well with the subjective sensation of the subjects. Voluntary pelvic floor contraction decreased the subjective intensity of the desire to void sensation as well as sympathetic skin response activity for the same short period. During voiding sympathetic skin responses almost complete absence of sympathetic skin responses was observed. CONCLUSIONS: Sensations arising from the bladder induce combined activation of sympathetic skin responses and pelvic floor activity. This coherence indicates synchronized activation and inactivation of the autonomic and somatic pathways necessary for appropriate urine storage and coordinated voiding. Our observations may introduce a new approach for objectively assessing subjective sensations arising from the urinary tract.

Botulinum-A toxin for treating detrusor hyperreflexia in spinal cord injured patients: a new alternative to anticholinergic drugs? Preliminary results.

PURPOSE: We evaluated the efficacy of botulinum-A toxin injections into the detrusor muscle in patients with spinal cord injury, detrusor hyperreflexia and urge incontinence resistant to anticholinergic drugs. The purpose of treatment was to suppress incontinence episodes and increase functional bladder capacity. MATERIALS AND METHODS: Included in our prospective nonrandomized study done at 2 clinics were 31 patients with traumatic spinal cord injury who emptied the bladder by intermittent self-catheterization. These patients had severe detrusor hyperreflexia and incontinence despite a high dose of anticholinergic medication. Pretreatment evaluation included a clinical examination and complete urodynamic investigation. Under cystoscopic control a total of 200 to 300 units of botulinum-A toxin were injected into the detrusor muscle at 20 to 30 sites (10 units per ml. per site), sparing the trigone. Clinical and urodynamic followup was planned for 6, 16 and 36 weeks after treatment. Patients were asked to decrease their intake of anticholinergic drugs during week 1 after treatment. RESULTS: Of the 21 patients 19 underwent a complete examination 6 weeks after the botulinum-A toxin injections, and 11 at 16 and 36 weeks. At the 6-week followup complete continence was restored in 17 of 19 cases in which anticholinergic medication was markedly decreased or withdrawn. Less satisfactory results in 2 cases were associated with an insufficient dose of 200 units botulinum-A toxin. After the injections overall mean reflex volume and mean maximum cystometric bladder capacity plus or minus standard deviation significantly increased from 215.8 +/- 90.4 ml. to 415.7 +/- 211.1 (p <0.016) and 296.3 +/- 145.2 to 480.5 +/- 134.1 (p <0.016), respectively. There was also a significant decrease after treatment in mean maximum detrusor voiding pressure from 65.6 +/- 29.2 cm. water to 35 +/- 32. 1 (p <0.016). Mean post-void residual urine volume catheterized at the end of the urodynamic examination increased significantly from a mean of 261.8 +/- 241.3 ml. to 490.5 +/- 204.8 (p <0.016). Moreover, autonomic dysreflexia associated with bladder emptying that manifested as a hypertensive crisis during voiding disappeared after treatment in the 3 patients with tetraplegia. Satisfaction was high in all successfully treated patients and no side effects were observed. Ongoing improvement in urodynamic parameters and incontinence was already present in all patients reevaluated at 16 and 36 weeks. CONCLUSIONS: Botulinum-A toxin injections into the detrusor seem to be a safe and valuable therapeutic option in spinal cord injured patients with incontinence resistant to anticholinergic medication who perform clean intermittent self-catheterization. Successfully treated patients become continent again and may withdraw from or markedly decrease anticholinergic drug intake. A dose of 300 units botulinum-A toxin seems to be needed to counteract an overactive detrusor. The duration of bladder paresis induced by the toxin is at least 9 months, when repeat injections are required.

Sildenafil in the treatment of sexual dysfunction in spinal cord-injured male patients.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of sildenafil in the treatment of erectile dysfunction (ED) in spinal cord-injury (SCI) patients. Moreover, we looked for neurological conditions permitting therapeutic success and for the ideal dose needed to achieve sufficient erections. METHODS: 41 SCI patients were prospectively examined. Sexual dysfunction was assessed by means of anamnesis, the International Index of Erectile Function (IIEF) questionnaire, and neurological examination. Psychogenic erection capacity was tested by audiovisual stimulation and reflexive erection using a vibrator device. Neurophysiological recordings and cystomanometry were performed in parallel to clinical examinations. Neurophysiological recordings included sympathetic skin responses (SSR), pudendus somatosensory evoked potentials (pSSEP), and bulbocavernous reflex (BCR). Urodynamics aimed at classifying the neurogenic bladder dysfunction (upper motoneuron lesion versus lower motoneuron lesion). Intracavernous injection tests with PGE1 were performed in all patients to exclude major organic disease. 50 mg sildenafil was first given 3 times. Thereafter, the doses were adapted according to patients' reports. RESULTS: Clinically, 28 subjects preserved either reflexive erections (24) or psychogenic erections (4), 11 had both types and only 2 presented with a complete loss of erection. 38 patients (93%) had a positive response to sildenafil and reached a penile rigidity sufficient to permit sexual intercourse. 3 patients dropped out because of non-response despite having increased the dosis up to 100 mg. 22 patients (58%) showed functional erections 1 h after 50 mg sildenafil, whereas 14 (37%) required higher doses of 75-100 mg. By comparing the IIEF questionnaire scores before and after therapy, there was a significant improvement in erectile function and intercourse satisfaction from 9.2+/-4.4 SD) and 4.5 (+/-2.5 SD) to 25.5 (+/-4.2 SD) and 10.5 (+/-2.1 SD) points, respectively (p<0.05). Nearly 10% (4/41) suffered from side effects such as headache or dizziness. Two of them stopped therapy because of the side effects. At least 36 patients (88%) continue treatment with sildenafil. Absence of both psychogenic (nonsomesthetic supraspinally elicited) and reflexive (somesthetic spinally elicited) erections, confirmed by urodynamical and electrophysiological findings (SSR perineum, BCR and pSSEP), seems to exclude a successful treatment. In contrast, SCI male patients with preserved function of at least one component of the erection phenomenon (psychogenic/reflexive) responded well to sildenafil and the dose required to achieve erections sufficient for sexual intercourse did not differ between the two groups. CONCLUSIONS: Sildenafil proves to be a valuable and safe therapeutic management in ED of SCI patients. Therefore, patient acceptance and satisfaction are high. The most common dose required to achieve a satisfying erection is 50 mg. The efficacy of sildenafil depends on sparing of either sacral (S2-S4) or thoracolumbar (T10-L2) spinal segments which, in this study, have been shown to be of relevance in mediating psychogenic erections in male SCI patients. Complete disturbance of any neurogenic impulses excludes successful treatment.

Free/total prostate-specific antigen ratio can prevent unnecessary prostate biopsies.

OBJECTIVES: To evaluate the ability of free/total prostate-specific antigen (PSA) ratio to improve specificity of prostate cancer detection, compare Diagnostic Products Corporation (DPC) Immulite and Ciba Corning ACS 180 total (t)PSA assay, and define an assay-specific cutoff point and reflex range for DPC PSA ratio (PSAR). METHODS: In a prospective study, 206 men were enrolled with measurement of both assays. Group 1 consisted of 173 men with a suspicion of prostate cancer (PCA). Thirteen men with known PCA (group 2) and 20 men younger than 32 years (group 3) were used as control groups. RESULTS: Our results in group 1 (115 with benign prostatic hyperplasia [BPH], 58 with PCA) revealed a sensitivity of 82.7%, a specificity of 45.2%, and an accuracy of 57.8% for the DPC tPSA assay (cutoff point more than 4.0 ng/mL) within the entire PSA range. tPSA values of the ACS 180 assay were 1.97-fold higher. Within the tPSA gray zone of 2.5 to 10 ng/mL (66 BPH, 23 PCA), specificity and accuracy of DPC tPSA can be improved by using the DPC PSAR (cutoff point less than 19%) from 33.3% to 71.2% and 42.7% to 70.8%, respectively, maintaining the same sensitivity level of 69.6%. CONCLUSIONS: By combining tPSA testing with PSAR within the gray zone, 39.7% (25 of 63) of unnecessary biopsies can be saved, without missing any additional cancers compared with tPSA testing alone. The optimal reflex range for DPC PSAR is 2.5 to 10 ng/mL and the best PSAR cutoff point for biopsy criterion is less than 19% in our high-risk population, with a cancer yield of 34%. Because we still do not have an international PSA standard, it is important to use assay-specific "normal values" and PSAR cutoff points.

The effect of spinal manipulation on pain and prostaglandin levels in women with primary dysmenorrhea.

OBJECTIVE: The primary objectives of this study were to compare the effect of spinal manipulation vs. sham manipulation on a) circulating plasma levels of the prostaglandin F2a metabolite, 15-keto-13,14-dihydroprostaglandin (KDPGF2a), b) perceived abdominal and back pain and c) perceived menstrual distress in women with primary dysmenorrhea. DESIGN: This randomized clinical pilot study investigated the outcome measures before and after either a spinal manipulation treatment (SMT) or a sham manipulation. SETTING: All subjects were treated at the National College Chiropractic clinic, a private chiropractic clinic in the suburban Chicago area. PARTICIPANTS: Forty-five women with a history of primary dysmenorrhea were recruited from the local community. The volunteers ranged in age from 20-49 (mean age = 30.3 yr), and were entered into the study between April 1990 and January 1991. Twenty-four were randomly assigned to the spinal manipulation group and 21 were assigned to the sham group. INTERVENTIONS: Subjects treated with spinal manipulation were placed in a side-lying position with the bottom leg straight and the top leg flexed at the knee and hip. They received a high-velocity, short lever, low-amplitude thrust to all clinically relevant vertebral levels within T10 and L5-S1 and the sacroiliac joints. In the sham manipulation, subjects were placed in a side-lying position with both hips and knees flexed. Their manipulation consisted of a similar thrust administered to the midline base of the sacrum. OUTCOME MEASURES: Perceived abdominal and back pain were measured with a visual analog scale, and menstrual distress was measured with the Menstrual Distress Questionnaire. Both were administered 15 min before and 60 min after treatment. Blood samples were collected by venipuncture for the determination of plasma levels of KDPGF2a at the same times. The plasma was then assayed for KDPGF2a by radioimmunoassay. RESULTS: Analysis of covariance and paired Student's t tests were used for the statistical evaluation. Immediately after treatment, the perception of pain and the level of menstrual distress were significantly reduced by SMT. This reduction was associated with a significant reduction in plasma levels of KDGPF2a in the SMT group. A significant and similar reduction in plasma KDPGF2a also occurred in the sham group, indicating that a placebo effect was associated with a single sham intervention. CONCLUSIONS: This randomized pilot study suggests that SMT may be an effective and safe nonpharmacological alternative for relieving the pain and distress of primary dysmenorrhea. However, the large change in KDPGF2a observed in both treatment groups clearly indicates that further studies with more subjects, studied over a longer time frame, are needed to resolve the question of a placebo effect.