Case for pharmacotherapy development for underactive bladder.

Case for pharmacotherapy development for underactive bladder.: “

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Case for pharmacotherapy development for underactive bladder.

Urology. 2008 Nov;72(5):966-7

Authors: Chancellor MB, Kaufman J

PMID: 18774593 [PubMed – indexed for MEDLINE]

Restoration of bladder contraction by bone marrow transplantation in rats with underactive bladder.

Restoration of bladder contraction by bone marrow transplantation in rats with underactive bladder.: “

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Restoration of bladder contraction by bone marrow transplantation in rats with underactive bladder.

Biomed Res. 2007 Oct;28(5):275-80

Authors: Nishijima S, Sugaya K, Miyazato M, Kadekawa K, Oshiro Y, Uchida A, Hokama S, Ogawa Y

We attempted to increase bladder contraction by bone marrow cell transplantation in rats with underactive bladder due to bladder outlet obstruction (BOO). Twelve female rats were anesthetized with halothane to create BOO. After 1 month, the urethral obstruction was removed and they were divided into a transplant group and a sham-operated group (n = 6 each). Bone marrow cells (1 x 10(7) / 0.2 mL) isolated from green fluorescent protein transgenic rats were injected into the bladder wall of the transplant group. Rats from the sham-operated group received injection of culture medium alone. One month after transplantation, isovolumetric cystometry parameters and histological features of bladder were observed as well as intact control rats (n = 6). The amplitude of bladder contractions was larger and the interval between contractions was shorter in the transplant group than the sham-operated group, and there were no differences in these parameters between the transplant group and the control group. Some green fluorescent muscle layers were found in the bladder wall of the transplant group, and these layers were also labeled by anti alpha-smooth muscle actin antibody. These results suggest that transplanted bone marrow cells may improve bladder contractility by differentiating into smooth muscle-like cells.

PMID: 18000341 [PubMed – indexed for MEDLINE]

Underactive pharmaceutical bladder activity.

Underactive pharmaceutical bladder activity.: “

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Underactive pharmaceutical bladder activity.

BJU Int. 2007 Oct;100(4):945-6

Authors: Wyllie MG

PMID: 17822472 [PubMed – indexed for MEDLINE]

[Lower urinary tract dysfunction and diabetes mellitus]

[Lower urinary tract dysfunction and diabetes mellitus]: “

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[Lower urinary tract dysfunction and diabetes mellitus]

Prog Urol. 2007 May;17(3):371-8

Authors: Chartier-Kastler E, Robain G, Mozer P, Ruffion A

Diabetic neuropathy can induce multi-organ functional disease including lower urinary tract dysfunction. After a review of the various neurological lesions associated with diabetes mellitus, the authors describe the voiding disorders observed in diabetics and their specificity. These disorders, usually characterized by a large, flaccid, underactive bladder, must always be interpreted as a function of other diseases of the male or female pelvis that alter an often precarious balance. The management problems raised by this neuropathy are related to the fact that it may not be correctly diagnosed prior to a surgical procedure, for example. A better knowledge of the risk factors and natural history of diabetic bladder must therefore be promoted.

PMID: 17622061 [PubMed – indexed for MEDLINE]

Is the use of parasympathomimetics for treating an underactive urinary bladder evidence-based?

Is the use of parasympathomimetics for treating an underactive urinary bladder evidence-based?: “

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Is the use of parasympathomimetics for treating an underactive urinary bladder evidence-based?

BJU Int. 2007 Apr;99(4):749-52

Authors: Barendrecht MM, Oelke M, Laguna MP, Michel MC

An underactive urinary bladder (UUB), often occurring after surgery, can lead to urinary retention even in otherwise healthy people. We systematically reviewed published reports to determine whether the use of parasympathomimetic agents is warranted in patients with a UUB. Agents allegedly useful in treating UUB were identified from urology and pharmacology textbooks. A systematic search for randomized clinical trials in patients with UUB using these agents revealed 10 such studies. Controls typically received placebo or no treatment. While three studies reported statistically significant improvements relative to the control group, six did not and one even reported a significant worsening of symptoms. There was no evidence for differences between individual drugs, specific uses of such drugs, or in outcome measures. We conclude that the available studies do not support the use of parasympathomimetics for treating UUB, specifically when frequent and/or serious possible side-effects are taken into account.

PMID: 17233798 [PubMed – indexed for MEDLINE]

Demonstration of muscarinic and nicotinic receptor binding activities of distigmine to treat detrusor underactivity.

Demonstration of muscarinic and nicotinic receptor binding activities of distigmine to treat detrusor underactivity.: “

Demonstration of muscarinic and nicotinic receptor binding activities of distigmine to treat detrusor underactivity.

Biol Pharm Bull. 2010;33(4):653-8

Authors: Harada T, Fushimi K, Kato A, Ito Y, Nishijima S, Sugaya K, Yamada S

The present study was undertaken to examine whether distigmine, a therapeutic agent used to treat detrusor underactivity, binds directly to muscarinic and nicotinic receptors. We used radioreceptor binding assays and compared the effects of distigmine with those of neostigmine and donepedil. The inhibitory effect of distigmine on the blood acetylcholinesterase (AChE) activity was significantly weaker than that of neostigmine. Distigmine, neostigmine, and donepezil competed for specific binding sites of [N-methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS ) and [(3)H]oxotremorine-M in the bladder, submaxillary gland and cerebral cortex of rats in a concentration-dependent manner, indicating significant binding activity of muscarinic receptors. Distigmine displayed significantly higher affinity for binding sites of [(3)H]oxotremorine-M compared with those of [(3)H]NMS as revealed by large ratios of its K(i) value for [(3)H]NMS to that for [(3)H]oxotremorine-M, suggesting that it has preferential affinity for agonist sites of muscarinic receptors. Distigmine seemed to bind to the agonist sites of muscarinic receptors in a competitive manner. Repeated oral administration of distigmine caused a significant decrease in the maximal number of binding sites (B(max)) for [(3)H]NMS in the bladder and submaxillary gland but not cerebral cortex. Distigmine also bound to nicotinic receptors in the rat cerebral cortex. In conclusion, distigmine shows direct binding to muscarinic receptors in the rat bladder, and repeated oral administration of distigmine causes downregulation of muscarinic receptors in the rat bladder. The observed direct interaction of distigmine with the bladder muscarinic receptors may partly contribute to the therapeutic and/or side effects seen in the treatment of detrusor underactivity.

PMID: 20410601 [PubMed – in process]

Functional improvement in spinal cord injury-induced neurogenic bladder by bladder augmentation using bladder acellular matrix graft in the rat.

Functional improvement in spinal cord injury-induced neurogenic bladder by bladder augmentation using bladder acellular matrix graft in the rat.: “

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Functional improvement in spinal cord injury-induced neurogenic bladder by bladder augmentation using bladder acellular matrix graft in the rat.

World J Urol. 2007 Apr;25(2):207-13

Authors: Urakami S, Shiina H, Enokida H, Kawamoto K, Kikuno N, Fandel T, Vejdani K, Nunes L, Igawa M, Tanagho EA, Dahiya R

Spinal cord injury (SCI) rostral to the lumbosacral level causes bladder hyperreflexia and detrusor-sphincter dyssynergia (DSD), which are accompanied by bladder hypertrophy. We hypothesize that bladder augmentation using a bladder acellular matrix graft (BAMG) can improve the function of SCI-mediated neurogenic bladder. In female rats (n = 35), SCI was induced by transection of the spinal cord at the lower thoracic level. Eight weeks following spinalization, bladder augmentation using BAMG was performed after hemicystectomy of the hypertrophic bladder. Cystometrography was performed at 8 weeks after spinalization and again at 8 weeks after augmentation. Several urodynamic parameters were measured and the grafted bladder was histologically evaluated. Thirty one rats were alive 8 weeks after spinalization. Twenty two (71%) rats developed hyperreflexic bladders and nine (29%) rats had underactive bladders before bladder augmentation. Twenty six rats survived until 8 weeks after augmentation. Urodynamic parameters showed improvement in some bladder functions in both hyperreflexic and underactive bladders after augmentation. In addition, bladder compliance was increased in hyperreflexic bladders and decreased in underactive bladders. Bladder augmentation decreased bladder capacity in high-capacity rats and increased it in low-capacity rats. Histological evaluation showed complete regeneration of BAMG in SCI-induced neurogenic bladder at 8 weeks after augmentation. This is the first report suggesting that the voiding function in SCI-induced neurogenic bladder can be improved by augmentation using BAMG. Improved voiding function was accompanied by histological regeneration of BAMG.

PMID: 17221271 [PubMed – indexed for MEDLINE]

Aging and the underactive detrusor: a failure of activity or activation?

Aging and the underactive detrusor: a failure of activity or activation?: “

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Aging and the underactive detrusor: a failure of activity or activation?

Neurourol Urodyn. 2010 Mar;29(3):408-12

Authors: Smith PP

AIMS: To examine the known and potential contributions of motor, sensory, and biomechanical dysfunctions to the clinical problems of detrusor underactivity and detrusor hyperactivity/impaired contractility. METHODS: A review of the current literature on non-obstructive voiding dysfunction associated with aging was conducted. The functional impact of age-induced biomechanical tissue change via alterations in sensory transduction is considered. RESULTS: Impaired contractility has been regarded as etiologic of detrusor underactivity. However, an age-related degradation in detrusor contractility as the primary contributor to impaired bladder emptying has not been conclusively demonstrated. To the extent that detrusor contraction force and duration are dependent upon efferent nerve activity and thus reflex responses to sensory activity, there is a potential impact of impaired sensory function on voiding efficiency. Structural and functional tissue changes accompanying aging may result in altered bladder afferent function, with subsequent reflex impairment of detrusor voiding function. CONCLUSIONS: The relative contributions of motor, sensory, and biomechanical dysfunctions to impaired voiding performance independent of outlet obstruction associated with aging remain to be elucidated.

PMID: 19760756 [PubMed – in process]

Effect of lumbar epidural administration of neostigmine on lower urinary tract function.

Effect of lumbar epidural administration of neostigmine on lower urinary tract function.: “

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Effect of lumbar epidural administration of neostigmine on lower urinary tract function.

Neurourol Urodyn. 2010 Mar;29(3):443-8

Authors: Agarwal MM, Singh SK, Batra YK, Mavuduru R, Mandal AK

BACKGROUND: Neostigmine is cholinomimetic and is used for postoperative analgesia. Its urodynamics effects on voiding function have not been elucidated. MATERIALS AND METHODS: Adult patients without bothersome voiding symptoms planned for rigid cystoscopy under local anesthesia were enrolled. They underwent multichannel urodynamics (filling cystometry and pressure-flow study) before and 30 min after lumbar epidural administration of Neostigmine (2 microg/kg). RESULTS: Indications for cystoscopy were check examination for follow up of carcinoma urinary bladder (n = 3), staging for carcinoma cervix (5), and removal of ureteral stent (4). Patients’ mean age was 51.9 +/- 11.7 years and international Prostatic symptom score 2.34 +/- 3.41. A trend of decreased maximum cystometric capacity (MCC) was observed after Neostigmine (413.50 +/- 142.45 ml vs. 357.00 +/- 145.62 ml; P = 0.056) without any change in end-filling pressure. Five patients developed detrusor overactivity (DO) and one had increase in its amplitude (P = 0.031). Four patients developed rhythmic rectal contractions and one had increase in its amplitude (P = 0.219). There was no difference in any of the voiding parameters. Mean Visual Analog Pain Score (VAS scale 0-10) during cystoscopy for this group was significantly lower than that in a similar group of patients who did not receive Neostigmine prior to rigid cystoscopy (1.16 +/- 0.94 vs. 4.57 +/- 1.45; P = 0.0001). The drug was well tolerated in majority of the patients. CONCLUSION: Epidural Neostigmine is effective in providing analgesia during diagnostic rigid cystoscopy. It leads to development of DO and decrease in bladder capacity without any effect on voiding function. These findings may help clinicians to use it for transurethral procedure-related pain relief without apprehension of voiding difficulty.

PMID: 19260084 [PubMed – in process]

Two cases of giant vesical diverticulum in females

[Two cases of giant vesical diverticulum in females]: “

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[Two cases of giant vesical diverticulum in females]

Hinyokika Kiyo. 1985 Mar;31(3):489-94

Authors: Fujioka T, Matsui S, Adachi M, Banya Y, Ohinata M, Kubo T, Ohhori T

Two rare cases of giant vesical diverticulum without infravesical obstruction in female are presented. The first case, a 58-year-old female, was admitted because of diverticulum with continuous urinary infection, which was diagnosed by urological examinations for hematuria. The second case, a 58-year-old female, was admitted with the diagnosis of diverticulum, which was done by the gynecologist during laparotomy for the suspicion of a right ovarian cyst. Neither patient complained of difficulty in urination in spite of remarkable residual urine and no neurologic abnormalities were detected. The cystograms of the two cases revealed over-goose-egg sized diverticula and vesical capacity was over 800 ml, in both cases. The other urograms and endoscopy showed no evidence of vesical trabeculation or any obstructive changes of bladder neck or urethra in either case. Therefore, mucosal diverticulectomy in the first and total diverticulectomy in the second, was performed for the residual urine. Each surgical specimen showed the muscle layer of the walls. In the post-operative course, urination was improved in spite of the underactive detrusor pattern of the cystometry in the first case. But residual urine volume was not decreased after the operation in the second case. These two cases seem to be congenital vesical diverticulum. But it is hard to rule out the possibility of secondary diverticulum due to neurogenic disorders of urinary bladder.

PMID: 3927663 [PubMed – indexed for MEDLINE]