RIA / Vol. 37 / N.À 2 Study and evolution of the qualityof raw milk from dairy farms in thenorthwest of the province of Santa Feand south of the province of Santiagodel Estero, Argentina (1993 – 2009) REVELLI, G.R.1; SBODIO, O.A.2; TERCERO, E.J.2 A total of 10,704 raw milk samples from a bulk tank were collected on 55 dairy farms associated to the Coo- perativa Tambera y Agropecuaria Nueva Alpina Ltda. between 1993 and 2009. Physicochemical, microbiologicaland sanitary parameters were analyzed within the framework of the Comprehensive Milk Quality ImprovementProgram to determine the mean values that characterize the zone. The following values were found: Acidity:16.30 ± 0.96 °D, pH: 6.68 ± 0.04, Fat: 3.48 ± 0.24%, True Protein: 3.11 ± 0.12%, Lactose: 4.74 ± 0.16%, Ash:0.70 ± 0.09%, Total Solids: 12.18 ± 0.42%, Freezing Point: -0.530 ± 0.02 °C, Total Bacterial Count: 9.6 x 104± 2.2 x 105 CFU/ml, Somatic Cell Count: 407,000 ± 230,000 cells/ml and Antibiotic Residues: 99.64% Negative.The most significant correlations were: Fat vs Total Solids (r = 0.784; P < 0.001) and True Protein vs TotalSolids (r = 0.557; P < 0.001). The compositional quality of raw milk from dairy farms in the northwest of SantaFe and south of Santiago del Estero were studied over a period of 17 years and showed a significant improve-ment, particularly regarding the indicators that infer a high industrial value. Optimization of the producers' ma-nagement capacity and the operational quality of dairy farmers contributed to achieve these results.
Untitled19 Urinaryretention Jalesh N. Panicker, Ranan DasGupta, Sohier Elneil and Clare J. Fowler of the outflow tract. Urethrocystoscopy is then usuallyperformed.
Impairment of bladder emptying may manifest as com- Mechanical causes in men generally result from an plete or partial urinary retention, and be either acute or anatomical obstruction to the bladder outflow, due chronic. The conditions under which retention occur for example to an enlarged prostate gland, urethral are many and varied, indicating there must be many stricture, or even a phimosis. Prolonged obstruction different causes which effect the same end result.
(chronic retention) can eventually result in detrusor Acute complete urinary retention is not uncommon "failure" or hypocontractility. As a general rule it is following surgery irrespective of the operation site and advisable for a man with a longstanding neurological is attributed to pain and the effects of postoperative condition to be investigated urologically before analgesia, with full recovery of voiding when these ascribing new bladder symptoms to his neurological effects wear off. Although complete retention can occur disease: a urethral stricture may develop some years acutely, it may be due to a high post-void residual after prolonged catheterization during a period of volume, of which the patient may or may not be aware.
unconsciousness or paralysis in intensive care.
Partial retention may be discovered incidentally or as a In women, there is no specific diagnosis of bladder result of investigation of a patient reporting the sensa- outlet obstruction, as occurs in the men. However, tion of incomplete voiding in association with voiding external factors can obstruct the urethra. These difficulty or a poor stream. When a voiding disorder include urethral diverticulae, uterine and cervical occurs in conjunction with detrusor overactivity, as fibroids and vaginal wall cysts.
commonly occurs with spinal cord disease, it may beconceptually helpful to think of the high residualvolume as the result of "incomplete emptying." Functional urinary retention with associated Patients with retention may present to a urologist, uro-gynecologist or neurologist.
neurological dysfunctionSpinal cord disease is a common cause of incompletebladder emptying although this usually occurs in Causes of urinary retention combination with detrusor overactivity so that the The underlying causes of urinary retention may be clinical picture is dominated by urgency incontinence.
either structural or functional (Table 19.1).
Sometimes, however, the impaired emptying may bethe more prominent part of the disorder, resultingoccasionally in complete retention. An acute spinal Structural causes cord injury causing "spinal shock" will result in detru- Once a diagnosis has been made, most structural sor areflexia lasting some weeks (Chapter 15). Be the causes are amenable to surgical correction. Urological spinal cord pathology causing bladder dysfunction or gynecological assessment includes taking a history, acute or chronic, its other neurological features will genital and pelvic examination, and where indicated, be readily apparent: it is extremely unusual for a urodynamic studies and possibly specialized imaging spinal lesion to cause bladder dysfunction without Pelvic Organ Dysfunction in Neurological Disease: Clinical Management and Rehabilitation, ed. Clare J. Fowler,Jalesh N. Panicker & Anton Emmanuel. Published by Cambridge University Press. # Cambridge University Press 2010.
Section 3: Specific conditions Table 19.1. Causes for urinary retention Mechanical (anatomical) Congenital malformations Posterior urethral valves Prostate and bladder Gynaecological, e.g. leiomyomas,pregnancy, vaginal wall cysts Urethral, e.g. urethral diverticulumor cysts Stenosis and strictures Urethral stricture, bladder neckstenosis Bladder or urethral Urogenital prolapse Functional Neurological causes Detrusor external sphincter dyssynergia and Spinal cord injury or disease poorly sustained detrusor contraction Detrusor areflexia or hypocontractility Multiple system atrophy Lesion of conus medullaris orspinal roots Pure autonomic failure Radical pelvic surgery Non-neurological causes Primary failure of urethral sphincter relaxation Fowler's syndrome (FS) Anticholinergic drugs or thosewith anticholinergic activity Primary detrusor myogenic failure there being long tract signs on neurological examin- understanding neurogenic skeletal muscle weakness, ation. Normal lower limb-evoked potentials may be is not directly applicable to neurogenic bladder reassuring, as will a normal MRI of the spine, an disorders. Whereas damage to an anterior horn cell investigation which is frequently performed but rarely in the cord or its motor axon in a ventral root or reveals unsuspected abnormalities in this context.
peripheral nerve will result in denervated striated Incomplete bladder emptying has been identified muscle and flaccid paralysis, a sacral root lesion as a feature that can be used to distinguish between does not produce detrusor denervation. This is MSA and Parkinson's disease  and an increasing because the S2–S4 roots contain the preganglionic post-micturition residual volume has been demon- parasympathetics destined for ganglia in the pelvis strated as disease progresses in MSA  (Chapter 13).
from which short postganglionic fibers originate to Just occasionally complete urinary retention can be innervate the detrusor smooth muscle (Chapter 1) a presenting symptom of MSA, although on careful (Fig. 19.1).
clinical examination other neurological features will be So it is that subsacral cord or cauda equina lesions (Chapters 15 and 17) produce an insensate "decen- The neurological concept of "upper" and "lower tralized" bladder which may exhibit poor compliance motor neuron" lesion, which is fundamental for or detrusor overactivity, presumably due to preserved Chapter 19: Urinary retention Fig. 19.1. Whereas sphincter denervation is a consequence of sacral root injury, root injury or damage to the pelvic nerves in the pelvisproduces a "decentralized" bladder since the postganglionic innervation is intact.
urothelial-detrusor reflexes and continuing intact currently lacking. Presumably, this same condition sympathetic innervation, rather than an acontractile makes up a proportion of the women with unex- detrusor and urinary retention. Retention can, how- plained urinary retention.
ever, result from damage to the ganglia as may occurin the condition of pure autonomic failure with gan-glionic autoantibodies, or surgical damage to the gan- Fowler's syndrome (FS) glia and postganglionic fibers during radical pelvic Urinary retention in young women in whom no uro- surgery (Chapter 18). Incomplete emptying or com- logical, gynecological or neurological abnormality plete retention can also result from the small fiber can be identified present a diagnostic dilemma.
involvement of diabetic or amyloid neuropathy which Women experiencing otherwise unexplained urinary may affect the pre- and postganglionic innervation retention are more numerous than men and in a young (Chapter 18).
woman a primary failure of sphincter relaxation (FS) What may either be a neuropathy confined to should be suspected. Previously, isolated urinary the visceral innervation, or in infants a myopathy, retention in young women in whom no abnormalities can cause "visceral enteropathy." This can present as on routine tests could be found was purported to be of chronic idiopathic pseudo-obstruction (CIPO), a rare psychogenic or hysterical origin [7–13], although a syndrome characterized by gross distension of pre- disorder of sphincter relaxation in young women has dominantly the small bowel without any anatomical been recognized for several years. Moore observed or mechanical obstruction. Bladder dysfunction has urethral sphincter hypertrophy during cystoscopy been reported in 10–69% of patients with CIPO [3–5].
in a series of women with voiding dysfunction  Urodynamic investigations reveal similar changes to and Raz observed elevated urethral closure pressures those seen in diabetic cystopathy including detrusor in a group of young women with urinary retention and hypocontractilty, increased residual volume and postulated that their retention was due to spasticity of decreased bladder sensation . Many are able to void the striated urethral sphincter or pelvic floor .
with the Valsalva maneuver or using catheters.
Fowler and colleagues then recorded myotonia-like In men, there is an uncommon condition where electromyographic (EMG) activity in the striated painless urinary retention presents without a mech- urethral sphincter of women presenting with urinary anical cause or associated neurological disorder. They retention  and proposed that the urinary retention have neither accompanying constipation nor sexual was due to a primary impairment of sphincter dysfunction and extensive investigation fails to reveal relaxation .
any underlying abnormality. It has been speculatively Although the EMG activity sounds superficially proposed that this disorder is due to some abnormal- like myotonia, detailed analyses show that the charac- ity of the intrinsic afferent innervation, possibly loss teristic descending sound is due to a decelerating of the "myofibroblast" or interstitial cells, thought to component of a complex repetitive discharge  be an integral part of the bladder stretch-sensing (Fig. 19.2A). When a number of generators of this mechanism , although any evidence for this is type of activity are heard, the sound has been likened Section 3: Specific conditions Fig. 19.2. Electromyographic recording from the striated urethral sphincter of a woman in complete urinary retention. A. "Deceleratingburst." B. "Complex repetitive discharge." When heard over the audio output of the EMG machine, it is likened to the sound of helicopters.
Chapter 19: Urinary retention to that of underwater recordings of whale song .
Table 19.2. Fowler's syndrome: clinical features and laboratory Complex repetitive discharges without deceleration produce a sound like helicopters over the audio- amplifier of the EMG machine (Fig. 19.2B). Jitter analysis of the components of the complex repetitive Aged between onset of menarche and discharges shows that this is so low that it must be due to ephaptic transmission between muscle fibers generating repetitive, circuitous self-excitation. It is No evidence of urological, this abnormal activity which is thought to prevent gynecological or neurological disease relaxation of the sphincter and cause urinary reten- Retention with a volume in excess of tion or voiding dysfunction . Other studies have demonstrated an association between complex repeti- No sense of urinary urgency despite tive discharges and increased post-void residual high bladder volumes urine  and voiding dysfunction .
Straining does not help emptying At the time of the original description of FS, many of the patients were observed to be hirsute, obese Sense of "something gripping" or and to have menstrual irregularities and there difficulty on removing catheter appeared to be a clinical association with polycystic No history of urological abnormalities in ovaries (PCO) . This association is now no childhood or associated abnormalities better understood than when the observation was first of the urinary tract made, and although the coincidence of PCO and Association with polycystic ovarian retention is by no means inevitable, a hormonal syndrome and endometriosis basis for the EMG abnormality seems likely and it Raised urethral pressure (>50% has been proposed that it is the result of a hormonally expected value for age) dependent channelopathy . The same type ofsphincter disorder has not been found in men Increased sphincter volume (>1.8 ml on with otherwise unexplained retention. According to the recent work of O'Connell and colleagues Characteristic urethral sphincter EMG  the distal urethra is a constituent part of theclitoris, forming the "clitoro-urethrovaginal complex" and clearly the distal urethra has major sex- surgical procedure using regional or general anesthe- sia. That the surgical procedure can be distantfrom the pelvis and as minor as wisdom teeth extrac-tion suggests the significant factor is the general Clinical features and investigations anesthetic. In some cases it is possible to elicit a A retrospective study by Swinn et al. defined the prior history of poor voiding with an interrupted characteristic features of FS . Patients are typically flow with which the woman may have been uncon- young post-menarche females who become unable to cerned but indicating at least some pre-existing void and present with painless urinary retention, abnormality. Why then a transient event such as a having a demonstrated residual volume exceeding general anesthetic should precipitate retention which 1 l at some stage in the evolution of their disorder does not resolve remains unknown and has undoubt- (Table 19.2). Although they may experience pain if edly been the cause of a number of medicolegal bladder distension becomes extreme, they do not report the expected urgency at such a large bladder If a trial without a catheter fails, the woman is usually capacity. Straining does not help emptying and intui- introduced to clean intermittent self-catheterization tively women feel they must promote sphincter relax- and her loss of sensation of urgency and their large ation to void by whatever means they can.
capacity mean she can go for long intervals with- The women often report that there has been an out catheterizing. However, catheterization is often antecedent event prior to the onset of their retention, painful, particularly on removing the catheter, such as an obstetric, gynecological or urological with many women complaining of a sensation of Section 3: Specific conditions "something gripping" as the catheter is withdrawn.
The discomfort with self-catheterization appears tobe much greater for these women than is reportedby similarly aged young women with multiplesclerosis and it is not uncommon for the difficul-ties to be so extreme that a suprapubic catheter isrequired. This is clearly a thoroughly unsatisfactoryarrangement for an otherwise healthy youngwoman.
Routine cystometry demonstrates a large-capacity bladder without the usual sensations during the fillingphase, and filling is often stopped at 500 ml ongrounds of safety although the subject's capacity ismuch greater. The patient is then unable to initiate Fig. 19.3. UPP in woman with Fowler's syndrome.
voiding and no rise in detrusor pressure observed.
The diagnostic investigation is urethral sphincter EMG using a concentric needle electrode (see Chap- (SNM) and the evidence from functional brain ter 4), to detect the abnormality previous described.
imaging suggests the underlying mechanism of the However, despite paraurethral injection of local anes- retention is more complicated. That contraction of thetic first, which may itself be painful, this test is the striated urethral sphincter can inhibit detrusor uncomfortable and furthermore the information contraction and suppress bladder afferents is known obtained is qualitative rather than quantitative: from animal experiments , although this has "is there or is there not abnormal EMG activity?" been little studied as it is a difficult phenomenon to It provides only limited information about the investigate in animals. We do know that in health, severity of abnormality and expected resulting dys- urethral afferents are hard-wired in the spinal cord to function, and it is sometimes difficult to be sure that suppress sensation, inhibit bladder activity and mod- "sufficient abnormality" has been found to account erate ascending bladder signals  (Chapter 1).
for a woman's complete urinary retention. The ureth- This is the neural basis for the "pro-continence reflex" ral pressure does however give insight into the func- whereby voluntary contraction of the sphincter tional abnormality. Using an infusion technique reduces urgency, and it is enhancement of this reflex (withdrawal of an 8 Fr urethral catheter at 2 mm/s that is the basis for physiotherapy exercises to encour- while infusing saline at 2 ml/min), maximum urethral age pelvic floor contractions to control urgency closure pressure (MUCP) can be measured (Fig. 19.3) incontinence. Feed forward from the guarding reflex and typically women with FS are found to have may further activate the pro-continence reflex in resting values in excess of 100 cm of water .
health, both mechanisms combining to maintain The formula of 92 – age (in years) is used to derive the bladder control as the bladder fills. In FS it is expected pressure, based on the work of Edwards hypothesized that extreme involuntary sphincter con- and Malvern . Wiseman et al.  also proposed traction results in accentuation of the pro-continence that ultrasound measurement of sphincter volume was reflex to the point that bladder sensation is suppressed helpful to detect the hypertrophy of the striated sphinc- and detrusor contraction ter resulting from sustained overactivity; but operator Certainly an absence of sensation with gross bladder variability in this measurement has restricted its useful- filling is characteristic of this condition and further ness in the diagnostic algorithm for these patients.
implies that signals from the bladder reaching thebrain are abnormally weak. The recent surprisingresults of an fMRI research study provide confirm- Pathogenesis of retention ation of this hypothesis .
Initially the findings seemed to suggest that urinary Repeated bladder filling and emptying of only retention in these young women was simply the result 50 ml at the baseline "bladder empty" condition of chronic outflow obstruction owing to poor sphinc- showed widespread negative responses to bladder ter relaxation. However the restoration of detrusor infusion (appearing blue in Fig. 19.4) in six women Chapter 19: Urinary retention Fig. 19.4. Functional MRI study in Fowler's syndrome. Responses to bladder infusion for the six women, rendered (projected) on the brain surface.
Red ¼ activation; blue ¼ negative response. A. Session at baseline with a near-empty bladder. B. at baseline with a full bladder. C. After SNM anda near-empty bladder. D. After SNM and a full bladder. Positive responses (red) indicate activation by bladder infusion. Negative responses (blue)indicate that the fMRI signal is smaller during infusion than during withdrawal. For the session at baseline with an empty bladder (Fig. 19.2A),the brain responses to bladder infusion (relative to withdrawal) were almost exclusively negative. See plate section for color version.
with FS, quite different from the activations seen in being that bladder filling in these women elicits "normal" individuals. Negative responses indicate abnormally strong urethral afferent signals that that the fMRI signal is smaller during infusion than inhibit bladder afferent activity reducing input to during withdrawal, the interpretation of this finding (and so deactivating) the periaqueductal gray (PAG) Section 3: Specific conditions Fig. 19.5. Correlation between the defect in the interoception of filling, i.e. an abnormal negative response, and the maximumurethral closure pressure (MUCP), a proxy measure of the abnormality of sphincter activity, in the individual subjects. See plate sectionfor color version.
and higher centers. Furthermore a correlation was (and concomitant decreased residual volume) over demonstrated between the defect in the interoception 48–72 hours  (Fig. 19.6).
of filling (i.e. the abnormal negative responses) and A study by DasGupta and Fowler included assess- the maximum urethral closure pressure, a proxy ment of striated sphincter EMG and MUCP before measure of the abnormality of sphincter activity, and after SNM, and showed no overall change in in the individual subjects (Fig. 19.5).
these parameters in women with restored voiding Our understanding of the mechanism of action . Urodynamic data from that study showed that of SNM in FS has developed through a number of the restoration of voiding is not due to changes in experimental approaches including urodynamics, sphincter overactivity but an improvement in detru- electrophysiological, brain imaging and clinical obser- sor contractility: a surrogate measurement of "work vation. An elegant demonstration of the restoration of done" by the detrusor suggested that the restored sensation and its timing in relation to the start of voiding was achieved by overcoming obstructed neuromodulation was described by Swinn et al.
Within hours of switching on the stimulator for A PET study suggested SNM probably restored SNM, bladder sensations return and the woman is voiding in women with FS by resetting brainstem able to void again. In a study that measured the function . What was demonstrated with PET voided volumes and the post-micturition residual imaging was that with SNM afferent activity reached volumes before and after the onset of neuromodula- the midbrain , and more recently with functional tion, there continued to be increased volumes voided magnetic resonance imaging (fMRI)  it reached Chapter 19: Urinary retention Volume of urine
Time (hours relative to PNE insertion)
Fig. 19.6. Within hours of switching on the stimulator for sacral neuromodulation (SNM) bladder sensations return and the womanis able to void again. A study that measured the voided volumes and the post-micturition residual volumes before and after the onset ofneuromodulation showed that there continued to be increased volumes voided (and concomitant decrease in residual volume) over48–72 hours. From , with permission.
the PAG (Fig. 19.7). It is therefore hypothesized studies have demonstrated significant urodynamic that SNM blocks the urethral inhibition of afferent findings in patients receiving intrathecal and intra- information flow from the bladder, thus re-enabling venous opiates, including impaired bladder sensation, detrusor hypocontractility and increased bladder cap-acity with normal urethral pressures [36, 37].
The effect may be dose-related as evidenced by the Opiates and voiding dysfunction increased risk of postoperative retention with patient- Although the theory outlined above provides the controlled analgesia as compared to intramuscular main basis for understanding urinary retention in opioids . Tramadol in particular has been young women with FS, the role of medication in shown to have a potent effect in reducing detrusor causing retention, opiates in particular, has recently overactivity in experimental animal models [39, 40].
become the focus of attention. Drugs with anticholi- The Netherlands Pharmacovigilance Foundation nergic activity (e.g. antipsychotic drugs, antidepres- reported five cases where there was a temporal asso- sant agents and anticholinergic respiratory agents), ciation between transient voiding dysfunction or urinary retention with the use of tramadol .
steroidal anti-inflammatory drugs (NSAIDs) and cal- Animal studies suggest that the activation of µ cium channel antagonists  are well known to opioid receptors in the PAG region of the midbrain affect voiding but we have recently become increas- inhibit detrusor contractions, thus resulting in urin- ingly aware of the effect of opiates in causing a failure ary retention . Both men and women taking to void. Although notorious as a potent cause of these medications are similar to women with FS constipation, the role of opiates as a cause of urinary in that they lack sensations of urgency but by retention seems to be less well recognized. Previous contrast they can usually empty to completion.
Section 3: Specific conditions Fig. 19.7. PET imaging showed that with SNM afferent activity reached the midbrain  and more recently with functional magnetic resonanceimaging (fMRI)  the PAG and right insula showed activation. Reproduced with permission. See plate section for color version.
The effect of these medications on a patient with have neurological or urological disease, some of "incomplete" FS is not clear but it may well be syner- whom have personality traits which many medical gistic and precipitate complete retention. In a practitioners regard as "manipulative or immature." prospective study of 61 referrals to our department This has led to the observation that "Fowler's for investigation and management of urinary reten- syndrome does not keep good company." In retro- tion, the cause could be identified in only 19. How- spect women taking high doses of opiates almost ever, 24 of the 61 patients were using significant doses certainly comprised a cohort of such cases and of opiates and in 34 of them, no other cause for the possibility that the effect of opiates is to accentu- urinary retention could be identified  (Fig. 19.8).
ate the pathophysiological consequences of an over- This recent observation explains a longstanding diffi- active sphincter may explain why 29% of those culty for the originator of FS which has been the diagnosed with FS on the basis of abnormal sphincter defence of the proposal that there is an organic cause EMG and an elevated MUCP were also taking opi- for urinary retention in young women who do not ates  (Fig. 19.8).
Chapter 19: Urinary retention Fig. 19.8. Opiate use in a prospective study of women presenting with urinary retention (n ¼ 61) .
Recently, Elneil et al. performed a retrospective et al. showing 76.2% efficacy at 70.5 months  analysis of the outcome of "two-stage" sacral neuro- and Elhilali et al. showing efficacy of 78% at 77 modulation in treating 100 women with chronic urin- months . Importantly, De Ridder and colleagues ary retention, 25 of whom were on opiate medications showed that women with urinary retention due to FS prescribed by their general practitioners or pain phys- had a better outcome from SNM at five years than icians for symptomatic management of chronic back, those without an abnormal sphincter EMG (72% vs.
pelvic or abdominal pain. Eight of these women had 46%) . Our results were similar, with 78% versus been diagnosed with FS on the basis of their history, a 43% efficacy, respectively .
raised UPP and abnormal sphincter EMG and a fur- Having changed to the "two-stage" procedure (see ther eight had a suitable history and raised UPP but Chapter 7) in 2004, a recent, medium-term follow-up had not had a sphincter EMG test.
of 100 women showed that the efficacy of the first It is now being hypothesized that FS results in stage of the implant was 81% and an abnormal excessive levels of endogenous encephalins, possibly sphincter EMG was a predictor for responsiveness at the level of the sacral spinal cord , and that in . Stage 2 was carried out in 77 patients and com- some patients this may be compounded by the effect plete voiding was restored in 54 patients, improved of exogenous opiates. Sacral neuromodulation, but bladder emptying in 9 patients but failure in 14 not pudendal nerve stimulation, somehow success- patients. Of the 77 women, only 49 had had sphincter fully counteracts that pathological condition.
EMG but all had had UPP measurement. An elevatedUPP was found to predict a good response to stage 2but the EMG findings were inadequately powered to demonstrate an effect. A new surgical interven- In the analysis of our initial cohort of 60 women who tion was required in 40 patients either because of leg underwent percutaneous nerve evaluation (PNE) and pain or pain in relation to the battery site, lead dis- subsequent implant, when followed up with a mean placement or fracture, loss of efficacy or battery site interval of 7 years, 70% were voiding spontaneously . This is in keeping with the findings from other As mentioned above, 25% of this cohort was being centers of the longer-term efficacy of SNM as a treat- treated with opiates but the use of opiates was shown ment for non-obstructive retention, van Voskuilen to have no effect on the outcome of stage 1 or stage Section 3: Specific conditions 2, nor was it a determining factor for the need for access to the internet, more patients and their relatives revision surgery. A deduction that can be made from are becoming aware that SNM is an intervention that the observation that those taking and those not taking can restore voiding for some and they naturally seek opiates had a comparable response to SNM suggests out the opportunity to be treated by this intervention.
that its mechanism of action is likely to involve an The result is that both women and men with chronic anti-inhibitory effect of neurotransmitters common retention are being referred to centers that offer this in both groups, possibly at opiate receptors in the treatment, although only a small proportion may be cord or PAG. Recently Chen et al.  have demon- strated that the inhibitory effect of pudendal nerve That SNM restores voiding in FS is well estab- stimulation on bladder reflexes in experimental cats lished , its long-term efficacy has been shown to can be influenced by naloxone, suggesting an inhibi- be greatest in women with FS , and furthermore tory role of endogenous opioids as a mediator for the we now have a scientific basis for understanding how stimulation effect. However, pudendal nerve stimula- it works in this condition [31, 34]. The efficacy of SNM tion at standard frequencies has been found not to be in other causes of retention (most of which are of effective in restoring voiding in women with retention unknown cause) is much less certain . This pre- (personal communication, Dr. Spinelli), suggesting sents a problem when counseling patients, although that pudendal nerve stimulation and sacral neuromo- many centres operate a policy that it is reasonable to dulation produce a fundamentally different effect on carry out a PNE, or nowadays more likely stage 1 with the neural control of micturition. It is postulated that tined lead, to test for efficacy in each individual wish- SNM may specifically counteract an excessive level of ing to be considered for long-term SNM. Certainly the endogenous, and sometimes additional exogenous, indications for SNM seem to be widening and its effect in men with non-surgical urinary retention deservesfurther investigation.
Management of chronic urinaryretention and SNM Selection of patients with retention for SNM The alternatives for management of chronic urinary It is assumed that patients have had structural or retention in women are limited. Many patients are neurological diagnosis excluded or at least uncovered.
treated with a-blockers, urethral dilatation or ureth- Although a diagnosis of FS is now established as a rotomy with little long-term success. Working on the predictor for a good outcome for SNM [32, 47, 48], principle that a phosphodiesterase inhibitor might sphincter needle EMG is not an easy test for the increase nitric oxide availability in the sphincter and patient or electromyographer and the test is not thus improve sphincter relaxation, we treated five widely performed outside academic centers. However, women with FS in a placebo-controlled trial with urethral pressure profile is a standard urodynamic sildenafil but unfortunately without benefit .
investigation and it is recommended that this is more Although an early study of the effect of injection of widely used in the preoperative assessment of women botulinum toxin into the striated urethral sphincter with retention. It will be elevated in women with a  failed to restore voiding in women with FS, there primary disorder of sphincter relaxation (i.e. FS) but is some evidence that this is an intervention worth abnormally low in women who have urinary retention as a result of a damage to innervation of the sphincter Whilst no pharmacological has yet been dis- and detrusor. Consideration of patients taking opi- covered to be effective, many women face the pro- ates, which may either be the cause alone or a contrib- spect of indefinite, often uncomfortable intermittent uting factor to urinary retention , is a difficulty.
catheterization or a permanent drainage procedure Clearly if the dosage is such that the medication (either an indwelling catheter or a surgical urinary appears to affecting daily function or addictive behav- diversion procedure). This is an unsatisfactory solution iour patterns are evident, then steps to stop or reduce for young women and their problem is commonly it, although difficult to achieve, would seem to be a compounded by a deep dissatisfaction because they better medical approach than SNM.
may have had no explanation as to why they continue Since SNM it is a resource-intensive proce- to have chronic urinary retention. With increasing dure requiring a number of hospital visits and an Chapter 19: Urinary retention expensive implant, patients should be selected care- 16. Fowler CJ, Kirby RS. Abnormal electromyographic fully for their ability to understand the implications activity (decelerating bursts and complex repetitive of what the treatment involves and their own cap- discharges) in the striated muscle of the urethralsphincter in 5 women with persisting urinary ability to manage possible adverse events.
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of sacral nerve stimulation for urinary retention: 42. Matsumoto S, Levendusky MC, Longhurst PA, results 18 months after implantation. J Urol Levin RM, Millington WR. Activation of mu opioid Fig. 19.4. Functional MRI study in Fowler's syndrome. Responses to bladder infusion for the six women, rendered (projected) on the brainsurface. Red ¼ activation; blue ¼ negative response. A. Session at baseline with a near-empty bladder. B. at baseline with a full bladder. C. AfterSNM and a near-empty bladder. D. After SNM and a full bladder. Positive responses (red) indicate activation by bladder infusion. Negativeresponses (blue) indicate that the fMRI signal is smaller during infusion than during withdrawal. For the session at baseline with an emptybladder (Fig. 19.2A), the brain responses to bladder infusion (relative to withdrawal) were almost exclusively negative.
Fig. 19.5. Correlation between the defect in the interoception of filling, i.e. an abnormal negative response, and the maximum urethralclosure pressure (MUCP), a proxy measure of the abnormality of sphincter activity, in the individual subjects.
Fig. 19.7. PET imaging showed that with SNM afferent activity reached the midbrain  and more recently with functional magneticresonance imaging (fMRI)  the PAG and right insula showed activation. Reproduced with permission.
Proc. Natl. Acad. Sci. USA Vol. 93, pp. 3275–3279, April 1996 DUB-1, a deubiquitinating enzyme with growth-suppressing activity YUAN ZHU*, MARTIN CARROLL*, FEROZ R. PAPA†, MARK HOCHSTRASSER†, AND ALAN D. D'ANDREA*‡*Divisions of Pediatric Oncology and Cellular and Molecular Biology, Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA 02115; and