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Biomedical subjects

M D Craggs

Publications and source records attributed to M D Craggs.

At least 19 recordsLinked to original sources

Three-dimensional MRI of the male urethrae with implanted artificial sphincters: initial results.

The aim of this study was to develop a method for simultaneous 3D visualization of a new type of artificial urethral sphincter (AUS) and adjacent urinary structures. Serial MR tomograms were acquired from seven men after AUS implantation. 3D reconstruction was performed by thresholding original (positive) and inverted (negative) image intensity and by subsequently fusing positive and negative images. Results show that the bladder, cuff and balloons of the AUS of originally high intensity were imaged in 3D by thresholding the positive datasets. The urethrae and corpora cavernosa penis of originally low intensity were displayed in 3D by thresholding the negative datasets. Fusion of the positive and negative datasets allowed simultaneous visualization of the AUS complex and adjacent urinary structures. All the structures of interest were also clearly seen by interactive multiplanar reformatting. Coronal tomographic datasets provided better 3D and reformatted 2D images than sagittal and transverse datasets. This technique offers a simple means for evaluating the complex urethral anatomy and the AUS, and has potential for improved 3D visualization of many other complex morphological and pathological conditions.

Aged↗

Effects of repeated ejaculations on semen characteristics following spinal cord injury.

STUDY DESIGN: Prospective randomised controlled study. OBJECTIVE: To evaluate the effects of repeated ejaculation on semen characteristics following spinal cord injury (SCI) in a prospective randomised controlled study. SETTING: Spinal Research Centre, Stanmore, UK and Institute of Urology and Nephrology, London, UK. METHODS: A total of 74 patients with SCI above T10 were tested by vibro-ejaculation using a Ferticare penile vibrator (Multicept A/S Horsholm, Denmark) using a standardised technique. The ejaculate was examined according to WHO protocol. The successfully vibro-ejaculated subjects (n = 32) were randomised into a study group (n = 18) and a control group (n = 14). The patients in the study group vibro-ejaculated weekly for 3 months with semen analysis performed at baseline and then monthly. The control group vibro-ejaculated at baseline and at the end of the 3-month period. Two experienced observers performed the semen analysis independently. All measures were compared for statistical significance across the two groups at the beginning and at the end of the 3-month period using a two-tailed student t-test. Significance was determined at the 95% confidence interval (P < 0.05). RESULTS: In total, 10 patients in the study group and nine in the control group have completed the study so far. Six patients have dropped out of the study group and three from the control group for varied reasons. Two patients are currently enrolled in the study and control groups. The morphology and forward progression of sperm shows a statistically significant increase in the study group. The motility improves but is not statistically significant in the study group. No significant adverse effects were reported. CONCLUSIONS: We have shown in this unique randomised controlled study that repeated ejaculation does improve the sperm characteristics in SCI patients. It is suggested that SCI men should undergo repeated ejaculation for at least 3 months before trying intravaginal or intrauterine insemination techniques. If this fails then in vitro fertilisation can be used. This method promotes natural conception, is intimate and cost effective.

Adult↗

Does magnetic stimulation of sacral nerve roots cause contraction or suppression of the bladder?

AIMS: The aim of this study was to resolve the paradox as to whether magnetic stimulation of sacral nerve roots results in contraction or suppression of the bladder, in both normal individuals and patients with spinal cord injury (SCI). MATERIALS AND METHODS: Seven males with complete SCI and neurogenic detrusor overactivity (NDO) and five normal males were investigated. Bladder capacity and maximum cystometric capacity were determined, respectively, in these groups. Magnetic stimulation was applied to sacral nerve roots using a multi-pulse magnetic stimulator and coil. Stimulation was applied at half capacity, near-full capacity, and during NDO or voiding (in normal individuals). Single and intermittent bursts of stimulation were applied. RESULTS: Neither single nor intermittent bursts of magnetic stimulation of the sacral nerve roots resulted in significant bladder pressure rises. Occasionally, following cessation of the magnetic stimulation bladder contractions were seen in patients with NDO. These contractions had an unpredictable and variable latency. As previously reported, magnetic stimulation suppressed NDO in patients with SCI, and suppressed voiding in normal individuals. CONCLUSIONS: Bladder contractions are occasionally observed in patients with NDO following withdrawal of stimulation. This phenomenon hypothetically arises as a result of removal of the bladder suppression provided by magnetic stimulation, rather than direct motor pathway stimulation (as has been reported by others). The ability of sacral magnetic stimulation to suppress detrusor contractions is reaffirmed.

Adult↗

Electromyographic detection of purinergic activity in Guinea pig detrusor smooth muscle.

PURPOSE: We recorded nerve mediated extracellular electrical activity from guinea pig detrusor smooth muscle strips using suction electrodes and determined the electrophysiological origins of this signal and its relationship to contractile activity. MATERIALS AND METHODS: Mucosa-free detrusor strips were prepared from male guinea pigs sacrificed under Home Office license, physiologically superfused, attached to a pressure transducer and electrically stimulated (0.1 millisecond pulses). Electrical signals recorded using a bipolar reversible suction electrode were processed and recorded simultaneously with changes in strip tension. The effect of superfusion with alpha, beta-methylene adenosine triphosphate (ATP), atropine, extracellular [CaCl(2)] depletion and pharmacological Ca2+ channel blockade on the electrical and mechanical signals was determined. RESULTS: A biphasic electrical signal was consistently recorded from 37 detrusor strips. The signal was sensitive to graded reduction in [CaCl(2)] of the superfusate and abolished by tetrodotoxin in 7 preparations. The signal was also abolished in 12 preparations by alpha, beta-methylene ATP in association with an attenuated contraction but not significantly reduced in amplitude (p = 0.77) despite a significant reduction in tension with atropine (mean plus or minus SD 74% +/- 14% of control, p <0.001). The signal was attenuated to a mean maximum of 9% +/- 3% of control by pharmacological Ca2+ channel blockade and the remaining signal was abolished by alpha, beta-methylene ATP. CONCLUSIONS: The extracellular electrical signal recorded from guinea pig detrusor strips using suction electrodes originates from a purinergic mechanism. Although an atropine sensitive component may be present, the signal does not depend on cholinergic neuromuscular transmission and would not be expected to be generated by normal human detrusor. Provided that the electrophysiological basis of purinergic neurotransmission in guinea pig and human bladders is similar suction electrodes may be a valuable tool with which to evaluate in vitro and clinically by electromyography the pathological purinergic neuromuscular transmission that can be expressed in addition to normal cholinergic mechanisms in detrusor from dysfunctional human bladders.

Adenosine Triphosphate↗

[Effects of peripheral functional electrostimulation in obstructive bladder instability].

INTRODUCTION: The aim of this study was to assess the effects of peripheral functional electrical stimulation (FES) in patients with detrusor instability (DI) secondary to obstructive Benign Prostatic Hyperplasia (BPH). SUBJECTS, MATERIAL & METHODS: Nine patients with urodynamically proven DI secondary to BPH were investigated. Sensory and pudendo-anal reflex thresholds were determined in each patient to individually optimise FES. A standard fill cystometry was then performed and individually optimised FES was given when an unstable detrusor contraction occurred. Non stimulated contractions were used as controls. The effects of FES were analysed by measuring the mean area under the unstable pressure curves with and without FES and were expressed as percentage suppression. RESULTS: The percentage suppression in the mean area under the curves after stimulation was < 10%. There was no statistically significant difference between controls and FES using a two tailed, paired students t-Test (p > 0.1) at 95% confidence level (p > or = 0.05). CONCLUSION: FES did not significantly suppress unstable bladder contractions in patients with DI secondary to BPH. This finding suggests that obstructive DI does not depend on sacral reflex mechanisms and supports the view that it has a peripheral pathophysiological origin (myogenic and/or nerve endings).

Electric Stimulation Therapy↗

Neuromodulation through sacral nerve roots 2 to 4 with a Finetech-Brindley sacral posterior and anterior root stimulator.

STUDY DESIGN: Investigation of five patients receiving an implant, using laboratory cystometry and self-catheterisation at home. OBJECTIVES: To use the established Finetech-Brindley sacral root stimulator to increase bladder capacity by neuromodulation, eliminating the need for posterior rhizotomy, as well as achieving bladder emptying by neurostimulation. SETTING: Spinal Injuries Unit, Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK. METHODS: Five patients underwent implantation of a Finetech-Brindley stimulator without rhizotomy of the posterior roots. This was either a two channel extradural device (four cases) or a three channel intrathecal device (one case). In each patient, the implant was configured as a Sacral Posterior and Anterior Root Stimulator (SPARS). Postoperatively, repeated provocations using rapid instillation of 60 ml saline were used to determine the relative thresholds for neuromodulation using each channel. The effect of continuous neuromodulation was examined in the laboratory using slow fill cystometrograms, and conditional stimulation was also studied (neuromodulation for 1 min to suppress hyperreflexic contractions as they occurred). In one patient, neuromodulation was applied continuously at home, and volumes at self catheterisation recorded in a diary. RESULTS: Reflex erections were preserved in each patient. In three patients, detrusor hyperreflexia persisted postoperatively and neuromodulation via the implant was studied. In these three patients, the configuration was: S2 mixed roots bilaterally (channel B), and S34 bilaterally (channel A). Both channels could be used to suppress provoked hyperreflexic contractions, with the S2 channel effective at a shorter pulse width than S34 in a majority of cases. Continuous stimulation more than doubled bladder capacity in two out of three patients during slow fill cystometry. Conditional stimulation was highly effective. In the one patient who used continuous stimulation at home, bladder capacity was more than doubled and the effect was comparable with anticholinergic medication. Bladder pressures >70 cm water could be achieved with intense stimulation in three patients, but detrusor-external urethral sphincter dyssynergia (DSD) prevented complete emptying. CONCLUSIONS: Neuromodulation via a SPARS was effective and may replace the need for posterior rhizotomy. However, persisting DSD may prevent complete bladder emptying and warrants further investigation.

Adult↗

The acute effects of continuous and conditional neuromodulation on the bladder in spinal cord injury.

STUDY DESIGN: Laboratory investigation using serial slow-fill cystometrograms. OBJECTIVES: To examine the acute effects of different modes of dorsal penile nerve stimulation on detrusor hyperreflexia, bladder capacity and bladder compliance in spinal cord injury (SCI). SETTING: Spinal Injuries Unit, Royal National Orthopaedic Hospital, Stanmore, Middlesex, UK. METHODS: Fourteen SCI patients were examined. Microtip transducer catheters enabled continuous measurement of anal sphincter, urethral sphincter and intravesical pressures. Control cystometrograms were followed by stimulation of the dorsal penile nerve at 15 Hz, 200 micros pulse width and amplitude equal to twice that which produced a pudendo-anal reflex. Stimulation was either continuous or in bursts of one minute triggered by a rise in detrusor pressure of 10 cm water (conditional). Further control cystometrograms were then performed to examine the residual effects of stimulation. RESULTS: Bladder capacity increased significantly during three initial control fills. Continuous stimulation (n=6) significantly increased bladder capacity by a mean of 110% (+/-Standard Deviation 85%) or 173 ml (+/-146 ml), and bladder compliance by a mean of 53% (+/-31%). Conditional stimulation in a different group of patients (n=6) significantly increased bladder capacity, by 144% (+/-127%) or 230 ml (+/-143 ml). In the conditional neuromodulation experiments, the gap between suppressed contractions fell reliably as bladder volume increased, and the time from start of stimulation to peak of intravesical pressure and 50% decline in intravesical pressure rise was 2.8 s (+/-0.9 s) and 7.6 s (+/-1.0s) respectively. The two methods of stimulation were compared in six patients; in four out of six conditional neuromodulation resulted in a higher mean bladder capacity than continuous, but the difference was not significant. CONCLUSIONS: Both conditional and continuous stimulation significantly increase bladder capacity. The conditional mode is probably at least as effective as the continuous, suggesting that it could be used in an implanted device for bladder suppression.

Adult↗

A new approach to recording the electromyographic activity of detrusor smooth muscle.

PURPOSE: Extracellular recordings from the whole intact mammalian bladder of the electrical events leading to contraction of the organ have been elusive for almost 50 years despite the widespread potential applications of such a technique. The principal problem is the need to isolate the small real signals reflecting membrane depolarization from the large electromechanical artifact generated as the organ contracts. In this preliminary study we determined whether electrical signals may be isolated and verified as biological using extracellular bipolar reversible suction electrodes. MATERIALS AND METHODS: Six whole excised guinea pig bladders were mounted in an especially constructed organ bath. Electrical activity resulting from nerve stimulation of the organ was recorded using a novel 10 bipolar Pt/PtCl suction electrode simultaneously with changes in intravesical pressure. Mechanical and pharmacological control experiments were performed to determine the true origin of these signals. RESULTS: A predominantly biphasic electrical signal of a mean amplitude plus or minus standard deviation of 647 plus or minus 301 microV. and a mean duration of 293 plus or minus 51 milliseconds was consistently recorded from the serosal surface of all guinea pig bladders. In all cases the electrical signal and mechanical response to stimulation were completely abolished by 1 microM. tetrodotoxin. The signal always preceded any change in intravesical pressure. It was sensitive to changes in the CaCl2 concentration of the superfusate, abolished by purinergic but not cholinergic neuromuscular blockade and independent of electromechanical artifact. CONCLUSIONS: In this preliminary report we describe a novel technique by which nerve mediated detrusor electrical activity leading to contraction of the whole intact guinea pig bladder may be isolated from artifact and verified as real. We hope that development of this technique may enable its application to the in situ human bladder. However, to our knowledge whether electromyographic activity may be recorded from human detrusor remains to be determined.

Animals↗

Neuromodulation by implant for treating lower urinary tract symptoms and dysfunction.

OBJECTIVE: Patients with irritative micturition complaints, pelvic pain, involuntary urine loss or urinary retention are sometimes difficult to treat. The advent of direct sacral nerve stimulation offers a therapeutic alternative if conservative measures fail and surgery is considered. This paper reviews therapeutic neuromodulation by implant for treating lower urinary tract symptoms and dysfunction. METHODS: The international literature is reviewed on topics such as the physiological basis of neuromodulation, techniques of acute testing and chronic implantation, and clinical results. Future developments and ways for possible improvement are discussed. RESULTS: The mode of action of neuromodulation is probably through restoring the correct balance between excitatory and inhibitory impulses from and to the pelvic organs at a sacral and supra-sacral level. Depending on the predefined success criteria, average success rates of definitive implants vary from 50 to 70%. From the data it seems that patients with urge incontinence and urinary retention are the best candidates for neuromodulation. In the literature the lack of standardisation of selection criteria, stimulation parameters and definitions of success is striking. CONCLUSIONS: Neuromodulation by implant is a useful therapeutic alternative. It should at least be considered in patients with therapy-resistant urge incontinence and urinary retention before proceeding to surgery. Issues such as underlying physiology, methodological standardisation, technical improvements, and patient selection must be addressed in future research.

Animals↗

Acute suppression of idiopathic detrusor instability with magnetic stimulation of the sacral nerve roots.

OBJECTIVE: To assess the effect of magnetic stimulation of the S3 nerve root on unstable contractions in patients with idiopathic detrusor instability. PATIENTS AND METHODS: Twelve patients with idiopathic instability were studied. The S3 nerve root was localized by mapping the response of the toe flexor muscles and anal sphincter to magnetic stimulation at different sites. Unstable contractions were provoked by rapidly infusing saline into the bladder and the effect of magnetic stimulation of S3 on contractions was assessed. RESULTS: Magnetic stimulation relieved the sensation of urinary urgency and reduced the duration and amplitude of provoked contractions in all patients. Stimulation reduced the area under the pressure/time curve by 80-98%. In some patients there was a shortlived residual suppressive effect lasting up to 90 s. CONCLUSIONS: Magnetic stimulation of S3 acutely abolishes unstable contractions in patients with idiopathic detrusor instability.

Electromyography↗

Neuromodulation of detrusor hyper-reflexia by functional magnetic stimulation of the sacral roots.

OBJECTIVE: To investigate the acute effects of functional magnetic stimulation (FMS) on detrusor hyper-reflexia using a multi-pulse magnetic stimulator. PATIENTS AND METHODS: Seven male patients with established and intractable detrusor hyper-reflexia following spinal cord injury were studied. No patient was on medication and none had had previous surgery for detrusor hyper-reflexia. After optimization of magnetic stimulation of S2-S4 sacral anterior roots by recording toe flexor electromyograms, unstable detrusor activity was provoked during cystometry by rapid infusion of fluid into the bladder. The provocation test produced consistent and predictable detrusor hyper-reflexia. On some provocations, supramaximal FMS at 20 pulses/s for 5 s was applied at detrusor pressures which were > 15 cmH2O. RESULTS: Following FMS there was an obvious acute suppression of detrusor hyper-reflexia. There was a profound reduction in detrusor contraction, as assessed by the area under the curves of detrusor pressure with time. CONCLUSIONS: Functional magnetic stimulation applied over the sacrum can profoundly suppress detrusor hyper-reflexia in man. It may provide a non-invasive method of assessing patients for implantable electrical neuromodulation devices and as a therapeutic option in its own right.

Adult↗

The effects of AMPA receptor antagonists on kindled seizures and on reflex epilepsy in rodents and primates.

Two potent glutamate antagonists, NBQX and GYKI 52466, that act selectively on non-NMDA receptors, have been tested for anticonvulsant activity in 3 models of reflex epilepsy (sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone rats and photically-induced myoclonus in Papio papio) and in amygdala kindled rats. Both compounds potently but transiently suppress reflexly-induced epileptic responses. GYKI 52466 also reduces behavioral seizures and afterdischarge duration in amygdala kindled rats, but with a lower potency than it suppresses reflex epilepsy. These data are similar to earlier results with antagonists acting selectively on NMDA receptors; they do not support a specific involvement of enhanced AMPA receptor sensitivity as a major factor in the expression of kindled seizures.

Acoustic Stimulation↗

The validation of a new ambulatory spike and wave monitor.

The reliability of a new pocket-size ambulatory monitor designed to automatically detect, indicate, measure and store spike and wave episodes in the EEG was determined. Eleven teenage children with epilepsy were studied. All had spike and wave episodes that were around 3/sec in frequency. A double-blind trial was carried out in which 2 experienced encephalographers scored independently the simultaneous records of the monitor and EEG. Correlation coefficients were calculated and, taking into account any inconsistencies between the 2 scorers' sets of data, a validation based on unity was determined for the monitor's record for each child. Of the 11 children studied only one had a validity measure that was less than 0.9, suggesting that when correctly adjusted for each child the monitor gave a reliable automatic indication of the duration and number of spike and wave events.

Adolescent↗