Transurethral electrovaporization of the prostate: is it any better than conventional transurethral resection of the prostate?

OBJECTIVE: To evaluate transurethral electrovaporization of the prostate (TUVP), compared with transurethral resection of the prostate (TURP), as a treatment for men with symptomatic benign prostatic enlargement (BPE). PATIENTS AND METHODS: In all, 235 men with symptomatic BPE in four hospitals in the South-East of England were randomized to TUVP (115) and TURP (120). Patients were assessed using the International Prostate Symptom Score (IPSS), the Short Form-36 (SF-36), EuroQol and sexual function questionnaire, uroflowmetry, ultrasonographic measurement of residual urine volume, pressure-flow urodynamics and transrectal ultrasonography. RESULTS: There was no statistically significant difference in the objective and subjective outcome after TURP and TUVP. The latter was associated with a lower transfusion rate than TURP but this did not result in an overall reduction in complications. There was no difference in the length of hospital stay. Overall, the two operations produced equivalent results and equivalent complication rates. CONCLUSION: TUVP is an effective treatment for symptomatic BPE, with results equivalent to TURP. TUVP has not led to the expected reduction in early postoperative morbidity or shorter hospital stays.

A new small-calibre diagnostic flexible cystoscope.

OBJECTIVE: To determine whether flexible cystoscopy with a prototype slim flexible instrument is less uncomfortable than flexible cystoscopy using a standard flexible cystoscope. PATIENTS AND METHODS: In all, 200 men scheduled to undergo flexible cystoscopy for the follow-up of transitional cell carcinoma of the bladder were randomized in equal groups to flexible cystoscopy using the standard instrument or using the prototype slim-scope. Each patient had 11 mL of 2% lignocaine gel instilled intraurethrally 5 min before the procedure. At the end of the procedure the patient was asked to complete a 100-mm non-graphical visual analogue scale to rate how uncomfortable the procedure was. RESULTS: The slim-scope was very significantly less uncomfortable than the conventional instrument (anova P < 0.001). The ease of use and views of the bladder were similar to those obtained with the conventional cystoscope. CONCLUSION: The slim-scope offers a significant benefit in patient comfort, with little loss of image quality or ease of use.

Electrical status epilepticus in slow wave sleep: prospective case study of a cortical hearing impairment.

The development of a central hearing impairment is described in a young girl with risk factors for hearing impairment that included mosaic Down syndrome, leukemia, and chemotherapy. This case is unusual in the prospective regularity with which hearing was assessed from birth. The diagnosis is electrical status epilepticus in slow wave sleep, a rare childhood disorder, which was associated with lack of responsiveness to auditory signals, regression of emerging speech and language and other cognitive skills, and abnormal electroencephalographic (EEG) activity in both hemispheres. Treatment of the disorder with anticonvulsant medications and steroids has ameliorated the condition by suppressing the abnormal EEG activity and allowing substantial improvements in cognitive and social skills, although communication skills are improving more slowly.

Profile of p53 expression in bladder and oral tumours. Effects of in vitro manipulations of p53 on the behaviour of established human tumour cell lines.

In this investigation the profile of p53 and epidermal growth factor receptor (EGFR) expression in tumour tissue biopsies of transitional cell carcinoma of bladder (TCC) and of oral-pharyngeal carcinoma (OP) were compared using an immunocytochemical staining method. In addition, various techniques including sodium dodecyl sulphate-polyacrylamide gel elecrophoresis (SDS-PAGE), colorimetric assay and gene transfection were used to investigate the influence of p53 on the behaviour of human tumour cell lines in vitro. The results showed that: (a) p53 was detectable in more than 45% of cases in both tumour types, although the profile and intensity of expression differed. (b) Concomitant strong expression of EGFR and p53 for TCC and OP was 21% and 38% (P>0.05%), respectively. (c) Treatment of tumour cells by either gamma radiation or by cisplatin resulted in the induction of p53 independent of the origin of the tumour. (d) Susceptibility of two cell lines, one with and one without constitutive expression of p53 showed that the expressing cells were more sensitive to gamma radiation (the percentage inhibition at 250 cGy was 57% versus -15%, P<0.01), and also cisplatin (the percentage inhibition at 1 microgram/ml was 71.0+/-6.0 versus 2.6+/-7.0, P<0.001). (e) Transfection of wild-type TP53 gene into a bladder tumour cell line resulted in a rapid cell apoptosis (by as much as 90%) whereas cells receiving mutated TP53 survived. A similar frequency of TP53 mutation in TCCs and OPs was observed. In addition, the pattern of p53 expression within the squamous type of TCC was similar to that in OPs. If the data from the in vitro studies could be translated into an in vivo setting, one could envisage a situation where the introduction of wild-type TP53 gene by gene transfection into tumour cells (independent of their TP53 gene mutational status), would prove to be beneficial. If the cellular TP53 gene is mutated, then an introduction of the normal TP53 gene would induce cells to undergo apoptosis. Alternatively, if TP53 is wild-type, then the increased levels of p53 expression would enable the cells to become more susceptible to DNA damaging treatments such as cisplatin or gamma radiation.

Age-related changes in auditory function of rhesus monkeys (Macaca mulatta).

The purpose of this study was to investigate the changes in auditory function associated with aging in rhesus monkeys (Macaca mulatta) as a model for age-related changes in humans. One advantage of using monkeys from the Wisconsin Regional Primate Research Center was that lifestyle factors such as diet and excessive noise exposure were controlled. Twenty younger (mean: 10 years, 9 months, S.D.=+/-6 months) and 20 older (mean: 25 years, 11 months, S.D.=+/-11 months) monkeys were used in this study. Cochlear function in these monkeys was measured with distortion product otoacoustic emissions (DPOAEs); neural function was measured with auditory brainstem responses (ABRs) and middle latency responses (MLRs). Older monkeys had (1) significantly smaller DPOAEs, (2) significantly smaller ABR peak amplitudes, and (3) significantly longer ABR peak latencies compared to younger monkeys. Overall, these results suggest that older monkeys have decreased cochlear and neural function to the level of the brainstem as compared to younger monkeys. The decrease in DPOAE level and the increase in age accounted for approximately 70% of the increase in peak IV latency.

Does endoscopic laser ablation of the prostate stand the test of time? Five-year results from a multicentre randomized controlled trial of endoscopic laser ablation against transurethral resection of the prostate.

OBJECTIVE: To determine the long-term objective and subjective outcome of patients with benign prostatic enlargement (BPE) treated by endoscopic laser ablation of the prostate (ELAP), as part of a multicentre randomized controlled trial of ELAP against TURP. PATIENTS AND METHODS: Initially, 151 patients with BPE were randomized to undergo either ELAP or TURP, starting in March 1992. ELAP was performed using the Urolasetrade mark fibre (Bard, Covington, GA, USA) in conjunction with a Nd:YAG laser source. All patients who had originally participated in the study were approached 5 years later to obtain a urological history, American Urological Association (AUA) symptom score and two measurements of urinary flow rate, with an ultrasonographic assessment of the postvoid residual urine volume (PVR). RESULTS: The mean duration of follow-up was 61 months; 109 patients were traced, comprising 69 who were alive and well, and had undergone no further bladder outlet surgery, 26 who had required revision surgery, 12 who were dead or terminally ill and three who had dementia. Both ELAP and TURP produced sustained improvements in mean AUA score, maximum flow rate and PVR, with respective values at 5 years of 6.3, 17.8 mL/s and 76 mL, and 6.5, 20.0 mL/s and 55 mL. Eighteen of 47 ELAP patients (38%) and eight of 51 (16%) TURP patients underwent revision surgery within the follow-up. CONCLUSION: ELAP and TURP produced similar subjective and objective outcomes at 5 years. The re-operation rate after ELAP was more than double that after TURP and suggests that ELAP should not be used routinely in the management of men with BPE.

Aging and middle ear function in rhesus monkeys (Macaca mulatta).

This study provided tympanometric data on rhesus monkeys (Macaca mulatta) and more support for this monkey as a good model for human peripheral auditory function. There have been few published reports concerning middle ear function in rhesus monkeys, and these experiments addressed that need. In the first experiment, peak acoustic admittance (Ytm) and ear-canal volume (Vea) were measured in 17 older adult monkeys and 16 younger adult monkeys. In the second experiment, middle ear resonance frequency was measured in eight younger adult monkeys and four older adult monkeys. Overall, peak Ytm, Vea, and resonance frequency were similar for monkeys and humans. Specifically, peak mean Ytm and mean Vea in monkeys were comparable to those values in human children. There was a trend for older monkeys to have decreased peak Ytm and Vea, but these trends did not reach statistical significance. There was a significant sex effect similar to what has been reported in humans. Male monkeys had larger peak Ytm values and larger Vea values compared with female monkeys regardless of age. Finally, there were no significant age or sex effects on resonance frequency.

An individualized, sensitive frequency range for early detection of ototoxicity.

OBJECTIVE: The aim of this study was to identify auditory frequencies at which serial threshold testing would provide the greatest sensitivity for early detection of ototoxicity. The overall objective is to develop a more time-efficient ototoxicity monitoring protocol. DESIGN: Threshold data were analyzed from 370 hospitalized patients treated with aminoglycoside antibiotics (AMGs) or cisplatin (CDDP) who received serial auditory monitoring before, during, and after treatment at conventional (0.25 to 8 kHz) and high (9 to 20 kHz) frequencies. RESULTS: For patients showing hearing changes due to ototoxicity, a frequency range was identified for its apparent high sensitivity to initial ototoxicity. This sensitive range is identified according to an individual's hearing threshold configuration, and is, therefore, unique for each patient. The range consists of five frequencies, generally separated by 1/6 octave, e.g., 8, 9, 10, 11.2, and 12.5 kHz. To determine frequencies and combinations of frequencies that were most often involved in ototoxicity detection, threshold data in the sensitive range were analyzed in detail. This analysis suggests that patients receiving treatment with AMG or CDDP can be monitored for hearing thresholds at only five frequencies, resulting in an 84% detection rate for AMG and 94% for CDDP compared with monitoring at all conventional and high frequencies. CONCLUSIONS: This comprehensive analysis supports earlier observations that a sensitive, limited frequency range exists in which serial threshold monitoring will provide early warning of ototoxicity before effects in the speech frequency range. This finding is now being evaluated in a prospective investigation.

The management of residual masses after chemotherapy in metastatic seminoma.

OBJECTIVE: To review our experience in management of residual masses after chemotherapy for metastatic seminoma. PATIENTS AND METHODS: The study comprised a review of 107 patients with metastatic seminoma, treated with initial chemotherapy from 1978 to 1996. Forty-three patients had residual masses detected by computed tomography after chemotherapy, while 64 achieved a complete response. Residual masses were classified radiologically as <3 cm or >/=3 cm and as well- or poorly defined. Of the patients with residual masses, 19 underwent surgery, while 24 were observed. RESULTS: Viable cancer was present in six of 11 patients with well-defined residual masses of >/=3 cm (positive histology in three of six undergoing surgery and site relapses in three of five observed), one of 14 patients with poorly defined masses of >/=3 cm (negative histology in nine undergoing surgery and site relapse in one of five observed), and in none of 17 patients with residual masses of <3 cm (negative histology in four undergoing surgery and no site relapses in 13 observed; one additional patient in this group died from treatment complications). CONCLUSION: Patients with a complete response after chemotherapy, a residual mass of <3 cm and a poorly defined residual mass of >/=3 cm can be observed, reserving intervention for recurrent or progressive disease. Well-defined residual masses of >/=3 cm should be resected because there is a 55% likelihood of persistent tumour.

Neural networks applied to retrocochlear diagnosis.

Methodologies have been developed, based on insights from signal detection theory, to evaluate quantitatively the diagnostic performance of tests. Several studies have demonstrated that, in fact, performance of a test battery can be inferior to the best of the tests it includes. These studies have been quite persuasive in damping enthusiasm for the test battery approach. Because the results of all tests in a battery were weighted equally in these studies, it is not surprising that an individual test with good sensitivity and specificity is more effective diagnostically than a combination of tests with poorer sensitivity and specificity. The authors of many of these studies were well aware of the limitations of this approach. In the present study, neural networks were applied to evaluate audiological tests used to predict retrocochlear pathology by differentially weighting the results of the tests in the battery. This technique avoids some of the limitations of previous approaches. Of the audiological tests evaluated in the present analysis, the superiority of the auditory brainstem evoked response (ABR) in predicting retrocochlear disease was again demonstrated. However, the results also demonstrated that identification accuracy could be improved by combining the ABR with other tests (in this case contralateral acoustic reflex at 2000 Hz, ipsilateral acoustic reflex at 2000 Hz, tone decay, and word recognition score). Further, it was demonstrated that performance could be improved over that obtained using dichotomous test measures (i.e., positive or negative presence of pathology) by using raw test measures in conjunction with ABR.

Local anaesthetic circumcision in adults.

Circumcision is a simple operation often performed under general anaesthesia. In this study, we assessed the suitability of local anaesthesia in 38 adult patients, 79.4% of whom suffered little or no discomfort. Infiltration of local anaesthesia caused moderate pain in 10 patients (29.4%) and severe pain in only one. The circumcision itself caused moderate pain in three patients and severe pain in another three (8.8%); 85% of patients expressed complete satisfaction.

Surgery as salvage therapy in chemotherapy-resistant nonseminomatous germ cell tumours.

OBJECTIVE: To review our experience of surgical staging for residual masses after chemotherapy in patients with nonseminomatous germ cell tumour (NSGCT) and positive tumour markers. PATIENTS AND METHODS: Of 107 patients with metastatic NSGCTs treated surgically after chemotherapy from 1978 to 1995, 30 (median age 30.5 years, range 20-52) had positive tumour markers. These patients were reviewed and the outcome compared with 77 patients who had normal tumour marker values. RESULTS: Of the 77 patients with negative markers undergoing surgical/pathological staging, 71 (92%) became continuously disease-free, including 37 of 50 (74%) with viable NSGCT in excised specimens. Seventeen of 30 (57%) with raised marker levels undergoing similar surgery for chemotherapy-resistant tumour became disease-free, including 11 of 22 with viable NSGCT in the excised specimens. CONCLUSION: Although the outcome after surgery is better in patients with negative tumour markers, it is clear that surgery is curative for patients with localized chemotherapy-resistant masses. There is a need for continued debate on the timing of salvage surgery and subsequent chemotherapy.

A single-centre observational study of surgery and late malignant events after chemotherapy for germ cell cancer.

OBJECTIVE: To review the impact of surgical staging after treatment on the late malignant events in an unselected group of patients treated with chemotherapy for germ cell cancer of the testis over the last 16 years. PATIENTS AND METHODS: The study comprised 256 patients treated between 1978 and 1994 who were reviewed for late relapse and development of second germ cell and non-germ cell cancer. RESULTS: At diagnosis, 142 patients had clinical stage 2, 30 stage 3 and 84 stage 4 disease; 57 patients relapsed within 20 months of treatment, while late germ-cell cancer relapses (> or = 24 months after treatment) occurred in six patients. Of patients relapsing early or late, 42% and 33%, respectively, received surgery after treatment. Only two of those relapsing late remain progression-free with further treatment. Four patients developed germ cell cancer in the contralateral testis, while six developed second non-germ cell cancers. CONCLUSION: Late events occurred in 6.2% of 256 patients in this series, from 29 to 141 months after treatment. Given that the late relapse rate of six of 256 (2.3%) is less than the incidence of mature teratoma at routine retroperitoneal lymph node dissection, more patients may eventually relapse. These results suggest that there might be a case to evaluate the use of ultrasonographic surveillance of the retroperitoneum and testis at 5, 10 and 20 years, in addition to extending routine surveillance.

Effect of stimulus level and frequency on ABR and MLR binaural interaction in human neonates.

Auditory brainstem (ABR) and middle latency (MLR) responses were evoked by click and tone-burst stimuli from human neonates. Electrophysiologic evidence of binaural interaction was measured by subtracting waveforms obtained for binaural stimulus conditions from waveforms obtained for the sum of right ear monaural and left ear monaural stimulus conditions. The effects of stimulus level and stimulus frequency on binaural interaction were evaluated by measuring the number, latency and amplitude of components found in the derived binaural interaction waveform, that is, binaural interaction components (BIC). BICs were more prevalent in the latency range of ABRs than for MLRs. Click and tonal stimuli were equally effective for deriving ABR-BICs, while tone-bursts were somewhat less effective than clicks for deriving MLR-BICs. Stimulus-response dependencies for ABR and MLR component latencies were apparent in monaural, binaural and binaural interaction waveforms. Normalized amplitudes for BICs showed that low-frequency tone-burst stimuli resulted in the largest values compared to click and high-frequency tonal stimuli. Comparison of these results with published results from adults demonstrated immaturity of binaural interaction in neonates.

Phase effects on the middle and late auditory evoked potentials.

A masking level difference (MLD) paradigm was used to investigate the presence of an electrophysiologic correlate of the psychoacoustic MLD in the middle and late auditory evoked potentials. In experiment 1, middle latency potentials were recorded in six normal-hearing young adults using vertex and temporal electrode montages. Tone bursts of 500 Hz presented in SoNo and Spi No conditions produced no threshold differences that were consistent with an MLD. In experiment 2, late latency potential (P2) thresholds to 500-Hz tone bursts under various phase conditions in noise were measured and compared to behavioral thresholds from the same stimuli. Ten subjects provided behavioral and P2 thresholds to SoNo, S pi No, So N pi S pi N pi, SmNo, and SmNm conditions. The rank order of behavioral and P2 thresholds and MLDs was consistent with previous literature on the behavioral MLD. Cortical contributions were confirmed as necessary for the production of the electrophysiologic MLD and, by analogy, the psychoacoustic MLD.

Postural adjustments produced by moving visual (horizontal optokinetic) patterns.

The effects of horizontal optokinetic stimulation (HOKS) on postural sway were examined in 30 normal subjects aged 20 to 75 years. Fixed-platform posturography was evaluated with the eyes open and closed and during HOKS (20-100 degrees/sec) in the rightward and leftward directions. Forward-backward sway was greater in amplitude than lateral sway under all viewing conditions. Sway amplitude was greater with eyes closed than with eyes open. HOKS significantly enhanced sway amplitude in both directions; however, significant differences occurred only between velocity extremes. Compared to younger subjects, older subjects showed greater forward-backward sway with eyes closed and greater lateral sway during HOKS. HOKS produces a visual cue that conflicts with the other two sensory signals regulating posture (vestibular and proprioceptive systems). Such conflicting visual cues may contribute to serious postural instability and falls in the elderly. The addition of optokinetic stimuli to fixed-platform posturography may enhance its diagnostic value.

Binaural phase effects in the auditory brainstem response.

This study investigated the possibility of a correlate of the masking level difference (MLD) in the auditory brainstem response (ABR), given that behavioral data indicate the brainstem origination of the MLD. Previous studies have reported MLD characteristics in the late auditory evoked potentials. In the present study, stimuli were presented in S(o)N(o) and S pi N(o) to female adults with normal hearing. In experiment 1, a binaural phasic difference potential (BPD) was derived by subtracting the suprathreshold ABRs to S(o)N(o) from S pi N(o) for tone pips of 500 to 4000 Hz. The magnitude of the BPD was inversely related to frequency. In experiment 2, thresholds to 500-Hz tone pips in S(o)N(o) and S pi N(o) were equal. In a case study of a subject with no behavioral MLD, the 500-Hz BPD was abnormal on one side, suggesting unilateral interruption of phase synchrony in the brain stem. Thus, the results of this study, in conjunction with previous studies on late potential correlates of the MLD, suggest that the ability to maintain phase information through the brain stem is necessary but not sufficient to generate the MLD.

Erectile dysfunction in multiple sclerosis. Associated neurological and neurophysiological deficits, and treatment of the condition.

Forty-eight men with multiple sclerosis and erectile dysfunction were evaluated. Emphasis was placed on the neurological features and the relationship between impotence and the bladder dysfunction in multiple sclerosis. Erectile failure was invariably associated with pyramidal signs in the lower limbs and with urinary symptoms. All of the men with impotence and marked pyramidal dysfunction in their legs were found by cystometric studies to have bladder hyperreflexia. The severity of the urinary symptoms was related to the degree of pyramidal impairment in the lower limbs. The posterior tibial and the pudendal cortical evoked potentials were abnormal in most of the men with multiple sclerosis and erectile failure. However, recording the pudendal cortical responses in patients with multiple sclerosis and impotence provided no more information than the tibial cortical evoked potentials. The neurological examination findings together with the results of the neurophysiological and cystometric tests suggest that erectile dysfunction in multiple sclerosis is due to spinal lesions situated proximal to the sacral cord. The feasability of papaverine intracorporeal injection therapy for men with multiple sclerosis and impotence was assessed. Papaverine intracorporeal injections produced satisfactory erections in the majority of the impotent men. Erectile failure in patients with multiple sclerosis was successfully managed for up to 2 years, by intracorporeal self-injection therapy.

High-frequency audiometric monitoring strategies for early detection of ototoxicity.

Therapeutic drugs such as the aminoglycoside antibiotics (AMG) and the chemotherapy agent cisplatin (CDDP) are known to cause irreversible hearing loss, typically affecting highest frequency hearing first with progression of loss to the lower frequency regions. Conventional (0.25-8 kHz) and high-frequency (9-20 kHz) serial hearing threshold monitoring was done in 123 hospitalized patients (222 ears) administered AMG or CDDP. Of ears showing a decrease in sensitivity corresponding with treatment, 62.5% demonstrated initial hearing loss solely in the high-frequency range, 13.5% first showed loss only in the conventional-frequency range, and 24.0% showed loss in both frequency ranges concurrently. Thus, if only high frequencies had been monitored, early change in auditory sensitivity would have been detected in 86.5% of these patients. Further analysis revealed a range of five frequencies, specific to each individual's hearing threshold configuration, in which initial ototoxicity appeared most likely to be detected. Testing only these five frequencies would have identified 89.2% of ears that showed change. The results of this study confirm the need to serially monitor auditory thresholds, especially in the high-frequency range, of patients receiving ototoxic drugs. A shortened five-frequency monitoring protocol is presented and suggested for use with patients unable to tolerate lengthy audiometric testing procedures.