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Biomedical subjects

Naoki Yoshimura

Publications and source records attributed to Naoki Yoshimura.

At least 91 records · Page 5Linked to original sources
PubMed2003

Tracheoplasty for long segment congenital tracheal stenosis: analysis of 29 patients over two decades.

PURPOSE: The authors determined the long-term outcome of patients who underwent surgical repair of long-segment congenital tracheal stenosis (LCTS) and compared the quality of cartilage graft and slide tracheoplasty techniques. METHODS: Twenty-nine patients underwent surgical repair of LCTS at 29 days to 9 years of age. In 26 patients, more than 50% of the entire length of the trachea was involved. The early 12 patients (1981 through 1992) were treated with a costal cartilage graft for tracheal reconstruction. The remaining 17 patients (1997 through 2002) were treated with slide tracheoplasty. For both procedures, a median sternotomy was preferred because of convenience when using extracorporeal circulation and for simultaneous repair of associated cardiovascular anomalies. RESULTS: Of the 12 patients who underwent a costal cartilage graft, 8 survived (66%). Six of these patients are free of disease, but 2 have persistent airway problems. Three patients died of residual stenosis and 1 of unrelated disease. Of the 17 patients who underwent slide tracheoplasty, 13 survived (76%), and 10 are free of disease. Three patients continue to require a stent because of tracheomalacia and granulation. Two patients died of cardiac failure, 1 of granulation, and 1 of aspiration pneumonia. CONCLUSIONS: The authors challenged LCTS with a unique surgical approach and succeeded in making an incurable disease curable. When the cartilage graft technique is compared with slide tracheoplasty, however, the latter is preferable because it preserves native tracheal tissue with less frequent complications.

Cartilage↗
PubMed2003

Vascular endothelial growth factor in children with congenital heart disease.

BACKGROUND: Children with cyanotic congenital heart disease may experience the development of abnormal vessels that become a source of significant morbidity. Abnormal vessel proliferation in these children may take several forms, including systemic-to-pulmonary collateral arteries, systemic-to-pulmonary venous collaterals, systemic venous collateral channels after bidirectional cavopulmonary anastomosis, and pulmonary arteriovenous malformations. However, no entity responsible for these abnormalities has been identified yet. This study determined whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor (VEGF) and whether elevated VEGF correlated with these abnormal vessels. METHODS: Mean systemic room air oxygen saturation (SpO2), blood cell counts (RBC), and serum VEGF levels were measured preoperatively. Samples were obtained from 61 children with acyanotic heart disease (group N) and 102 children with cyanotic heart disease (group C) before cardiac surgery. Postoperative catheterization was performed 1-month after the operation to evaluate the abnormal vessels in group C. RESULTS: The VEGF level was significantly elevated in group C (355.0 +/- 287.1 pg/mL) compared with group N (203.0 +/- 221.6 pg/mL; p < 0.001). VEGF levels in patients with a single ventricle associated with asplenia syndrome (n = 7) in group C were significantly elevated (711.9 +/- 443.5 pg/mL) compared with other patients. There was no significant correlation between VEGF level and SpO2 or RBC. Abnormal vessels were diagnosed in 19.6% (20/102) patients in group C. There was no difference in VEGF levels between the patients with abnormal vessels (336.8 +/- 182.5 pg/mL) and the patients without abnormal vessels (359.1 +/- 306.8 pg/mL). CONCLUSIONS: Children with cyanotic heart disease have elevated systemic levels of VEGF, especially in those patients with a single ventricle associated with asplenia syndrome. There was no significant relationship in VEGF levels between the patients with abnormal vessels and without these vessels.

Adolescent↗
PubMed2003

Cardioprotective effects and the mechanisms of terminal warm blood cardioplegia in pediatric cardiac surgery.

OBJECTIVES: Terminal warm blood cardioplegia has been shown to enhance myocardial protection in adult patients. However, the cardioprotective effects and the mechanisms of terminal warm blood cardioplegia in pediatric heart surgery were still unknown. METHODS: One hundred three consecutive patients were prospectively randomized to one of two groups. In the control group (n = 52), myocardial protection was achieved with intermittent hyperkalemic cold blood cardioplegia and topical cardiac cooling. In the terminal warm blood cardioplegia group (n = 51), this was supplemented with terminal warm blood cardioplegia before the aorta was declamped. Arterial and coronary sinus blood samples were analyzed to determine myocardial energy metabolism and tissue injury. RESULTS: There were no significant differences between the two groups in age (5.5 +/- 0.6 years in the control group vs 5.6 +/- 0.5 years in the terminal warm blood cardioplegia group), body weight (17.2 +/- 1.4 kg in the control group vs 19.8 +/- 1.7 kg in the terminal warm blood cardioplegia group), percentage of cyanotic heart diseases (50% in the control group vs 51% in the terminal warm blood cardioplegia group), number of patients who required right ventriculotomy (33% in the control group vs 39% in the terminal warm blood cardioplegia group), cardiopulmonary bypass time (194 +/- 12.1 minutes in the control group vs 177 +/- 8.6 minutes in the terminal warm blood cardioplegia group), aortic crossclamp time (83.3 +/- 5.9 minutes in the control group vs 82.3 +/- 5 minutes in the terminal warm blood cardioplegia group), lowest rectal temperature (27.4 +/- 0.3 degrees C in the control group vs 28.1 +/- 0.3 degrees C in the terminal warm blood cardioplegia group), and myocardial temperature (9.6 +/- 0.6 degrees C in the control group vs 9.6 +/- 0.7 degrees C in the terminal warm blood cardioplegia group). Spontaneous defibrillation occurred after reperfusion in 80% in the terminal warm blood cardioplegia group, which was significantly (P <.05) higher than the control group (62%). The lactate extraction rate at 60 minutes of reperfusion was significantly (P <.05) higher in the terminal warm blood cardioplegia group (9.0 +/- 2.8%) than the control group (-3.3 +/- 2.4%). The postreperfusion values of cardiac troponin T (7.4 +/- 0.6 ng/mL vs 11.2 +/- 1.0 ng/mL at 6 hours; 4.6 +/- 0.6 ng/mL vs 9.3 +/- 1.6 ng/mL at 18 hours) and heart-type fatty acid binding protein (137 +/- 28 ng/mL vs 240 +/- 30 ng/mL at 2 hours; 88 +/- 19 ng/mL vs 162 +/- 26 ng/mL at 3 hours) were significantly (P <.05 vs the control group) lower in the terminal warm blood cardioplegia group. CONCLUSION: Terminal warm blood cardioplegia enhances myocardial protection in pediatric cardiac surgery by an improvement in aerobic energy metabolism and a reduction of myocardial injury or necrosis.

Adolescent↗
PubMed2003

Secretion of A-type and B-type natriuretic peptides into the bloodstream and pericardial space in children with congenital heart disease.

OBJECTIVE: To determine the secretion of A-type and B-type natriuretic peptides into the bloodstream and pericardial space in children with congenital heart disease. METHODS: Plasma and pericardial fluid samples were obtained from 77 patients undergoing total correction for congenital heart disease. All patients underwent detailed right-sided and left-sided cardiac catheterization preoperatively. RESULTS: A-type natriuretic peptide levels in pericardial fluid were lower than those in plasma (33.0 +/- 23.1 versus 39.8 +/- 33.6 pg/mL, P <.05), and B-type natriuretic peptide levels in pericardial fluid showed marked elevations compared with those in plasma (231.9 +/- 305.6 versus 19.8 +/- 29.3 pg/mL, P <.0001). The A-type and B-type natriuretic peptide levels in plasma correlated with those in pericardial fluid (R =.522, P <.0001; R =.595, P <.0001). For A-type and B-type natriuretic peptide levels in plasma, the relation with biventricular volume had the highest correlation (R =.669, P <.0001; R =.652, P <.0001). The patients with a pulmonary-to-systemic flow ratio greater than 2 (n = 19) had high levels of natriuretic peptides not only in plasma (58.3 +/- 43.2, 40.5 +/- 49.4 pg/mL, P <.05) but also in pericardial fluid (44.4 +/- 31.5, 287.2 +/- 198.5 pg/mL, P <.05), and higher correlation between A-type and B-type natriuretic peptide plasma levels and left ventricular volume (R =.913, P <.0001; R =.787, P <.0001). CONCLUSIONS: B-type natriuretic peptide is secreted not only into the bloodstream but also into the pericardial space in children with congenital heart disease. Natriuretic peptide levels in plasma correlated well with biventricular volume. The left ventricle was considered to be the main source of secreted natriuretic peptides in the patients with a pulmonary-to-systemic flow ratio greater than 2.

Adolescent↗
PubMed2003

Pulmonary atresia with intact ventricular septum: strategy based on right ventricular morphology.

OBJECTIVES: Management strategy for pulmonary atresia with intact ventricular septum is controversial. We treated patients with this anomaly according to a management protocol based on our quantitative assessment of right ventricular morphology (index of right ventricular development and right ventricle-tricuspid valve index). In the present study, we reviewed a 20-year experience of the surgical treatment at our institution to define guidelines for selecting the appropriate type of surgical procedure. METHODS: Between April 1981 and June 2002, 45 consecutive patients with pulmonary atresia with intact ventricular septum underwent surgical treatment. Open transpulmonary valvotomy was performed in 27 patients and Blalock-Taussig shunt in 18 patients as the initial palliative procedure. Three patients who underwent a successful transpulmonary valvotomy alone in the neonatal period required no further operation. Definitive repair was performed in 32 patients. Biventricular repair was performed on 19 patients, one and a half ventricular repair in 3, and Fontan-type operation in 10. RESULTS: There were 1 early and 2 late deaths before the definitive operation in patients who underwent transpulmonary valvotomy. Two patients who had coronary artery interruption died 3 months and 13 years after the initial Blalock-Taussig shunt. There were 1 early and 2 late deaths after the definitive operation. Actuarial survival, including noncardiac death, was 91.1% at 5 years after the initial procedure and 81.5% at 10 years. CONCLUSIONS: We treated patients with pulmonary atresia with intact ventricular septum according to a management protocol based on our quantitative assessment of right ventricular morphology with good results.

Cardiac Catheterization↗
PubMed2003

Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity.

OBJECTIVES: An acute animal model for hyperactive bladder in rats was developed using intravesical infusion of protamine sulfate (PS), an agent thought to break down urothelial barrier function, and physiologic concentrations of potassium chloride (KCl). METHODS: Continuous cystometrograms (CMGs) were performed in urethane-anesthetized female rats by filling the bladder (0.04 mL/min) with normal saline followed by intravesical infusion of a test solution consisting of either KCl (100 or 500 mM) or PS (10 or 30 mg/mL) for 60 minutes. Subsequently, the 10 mg/mL PS-treated animals were infused intravesically with 100, 300, or 500 mM KCl. Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments. RESULTS: Unlike KCl (100 or 500 mM) or a low concentration of PS (10 mg/mL) alone, the intravesical administration of a high concentration of PS (30 mg/mL) produced irritative effects with a decreased intercontraction interval (by 80.6%). After infusion of a low concentration of PS, infusion of 300 or 500 mM KCl produced irritative effects (intercontraction interval decreased by 76.9% or 82.9%, respectively). The onset of irritation occurred more rapidly after 500 mM KCl (10 to 15 minutes) than after 300 mM KCl (20 to 30 minutes). Capsaicin pretreatment delayed the onset (approximately 60 minutes) and reduced the magnitude (intercontraction interval decreased by 35.5%) of irritative effects. CONCLUSIONS: Intravesical administration of KCl after PS treatment activates capsaicin-sensitive afferents and detrusor muscle and presumably capsaicin-resistant afferents. Modest, noncytotoxic affronts to urothelial barrier function can result in dramatic irritative responses. This model may be useful in the study of bladder irritation and hyperactivity.

Administration, Intravesical↗
PubMed2003

Intravesical liposome administration--a novel treatment for hyperactive bladder in the rat.

OBJECTIVES: To examine the effect of intravesical administration of liposomes (LPs) on chemically induced bladder hyperactivity in the rat. It has been suggested that interstitial cystitis (IC) is associated with a dysfunctional or leaky epithelium. Thus, enhancement of epithelial barrier function might be useful in the treatment of IC. LPs are vesicles that are concentric phospholipid bilayers separated by an aqueous compartment and can fuse with cells to provide a molecular film that can promote wound healing. METHODS: The intravesical pressure was recorded using a transurethral catheter in adult female Sprague-Dawley rats anesthetized with urethane (1.2 g/kg subcutaneously). Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments. Continuous cystometrograms were performed by slowly filling the bladder (0.04 mL/min) with solutions of varying compositions, including saline, acetic acid (AA, 0.1%), potassium chloride (KCl, 500 mM), protamine sulfate (PS, 10 mg/mL), LPs, PS/KCl, or LPs/KCl. The parameters measured included the intercontraction interval (ICI), amplitude of bladder contractions, compliance, and micturition pressure threshold. RESULTS: The ICI was decreased after exposure to AA (79.8% decrease) or PS/KCl (81% decrease); however, the ICI was not changed after LPs, PS, or KCl alone. The decreased ICI was partially reversed after infusion of LPs (172.8% increase) or LPs/KCl (63% increase), but was not significantly changed after switching to saline or KCl administration. Pretreatment with capsaicin delayed the onset of the irritative effects of AA by approximately 30 to 60 minutes, but had not changed the magnitude after 2 hours of infusion. CONCLUSIONS: Intravesical administration of PS/KCl or AA activates capsaicin-sensitive and capsaicin-resistant afferents in a time-dependent sequence that is partially reversed by LP infusion. We hypothesize that LPs might enhance the barrier properties of a dysfunctional uroepithelium and increase resistance to irritant penetration. Thus, intravesical LP administration could be a novel treatment of patients with IC.

Administration, Intravesical↗
PubMed2003

Implications of diabetes mellitus in urology.

The incidence of DM is rapidly growing among Americans. DM will rival cancer and heart disease in terms of cost and suffering. The National Institute of Health is tripling the research dollars that are spent on diabetic-related research in an attempt to combat this disease. Urologists are on the front line in the diagnosis and treatment of the complications of DM. The complications of DM that we reviewed in this article, diabetic cystopathy and diabetic ED, can occur in the early stage of DM and often progress in a silent fashion. More awareness and interest are needed to improve our understanding of diabetic complications in urology. Exciting new approaches in the treatment of diabetic cystopathy and ED are being investigated.

Clinical Trials as Topic↗
PubMed2003

Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway.

1. This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6-OHDA injection into the substantia nigra pars compacta. 2. In 6-OHDA-lesioned rats, voided volume per micturition (0.41+/-0.04 ml, mean+/-s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham-operated rats (0.67+/-0.07 ml). 3. Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder capacity (BC) (0.46+/-0.03 ml) in 6-OHDA-lesioned rats than in sham rats (0.72+/-0.06 ml). 4. SKF38393 (D1/D5 receptor agonist, i.v.) significantly increased BC in 6-OHDA rats without apparent effects in sham rats. SKF38393 applied intracerebroventricularly (i.c.v.) under urethane anesthesia also increased BC in 6-OHDA-lesioned rats and by a smaller increment in sham rats. 5. In contrast, quinpirole (D2/D3/D4 receptor agonist, i.v.) significantly reduced BC in sham and 6-OHDA-lesioned rats. Intrathecal injection of quinpirole similarly reduced BC in sham and 6-OHDA-lesioned rats. 6. PD128907 (D(3)-receptor agonist) did not have significant effects on BC in 6-OHDA-lesioned rats. 7. These results indicate that a rat model of PD exhibited bladder hyperactivity as observed in patients with PD, and that stimulation of D1/D5 dopamine receptors at a supraspinal site can suppress bladder hyperactivity in PD, whereas stimulation of D2/D4, but not D3, dopamine receptors had the opposite effect to reduce bladder capacity. Thus, D1/D5 dopamine receptor agonists might be effective in treating neurogenic bladder hyperactivity in PD.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2003

Surgical management of trabecular ventricular septal defects: the sandwich technique.

BACKGROUND: Surgical closure of trabecular ventricular septal defects is difficult and often unsuccessful. OBJECTIVE: We performed closure of trabecular ventricular septal defects by sandwiching the septum between 2 polyester felt patches placed in the left ventricle and right ventricle without ventriculotomy. METHODS: Eleven patients (7 boys and 4 girls) underwent a sandwiching closure at a mean age of 4.7 years (range, 0.4-9.7 years) and a mean weight of 16.7 kg (range, 4.6-52 kg). Associated cardiac malformations were present in 9 of the 11 patients. Seven patients had undergone previous operations. The trabecular ventricular septal defects are exposed through the tricuspid valve and also from the left ventricular side through a coexisting large perimembranous ventricular septal defect or through the mitral valve through an interatrial septostomy. Two forceps, one each from the right and left ventricular side, lead a 3F Nelaton catheter through the trabecular defect. An oversized circular polyester felt patch mounted on a 3-0 Nespolen suture attached to the Nelaton catheter is then passed into the left ventricle. The suture ends are then passed through a slightly smaller polyester felt patch on the right ventricular side of the septum. The Nespolen suture is then tied, thereby sandwiching the septum between the 2 patches. RESULTS: Time required for the procedure was less than 20 minutes in each case. There were no hospital deaths, and the postoperative course was uneventful in all patients. There was no residual shunt in 3 patients, and a minimal residual shunt was observed in 5 patients. Mild residual shunt was observed in 3 patients. Cardiac catheterization was performed 1 month postoperatively in 8 patients in whom residual shunt was noted on echocardiography. Five of 8 patients had a minimal residual shunt (pulmonary blood flow/systemic blood flow ratio = 1.0). Three patients had a residual shunt (pulmonary blood flow/systemic blood flow ratio = 2.0, 1.6, and 1.2). The patient with a pulmonary blood flow/systemic blood flow ratio of 2.0 had a "Swiss cheese" ventricular septal defect, and a residual shunt remained around the patch. However, the residual shunt decreased to a pulmonary blood flow/systemic blood flow ratio of 1.6 at examination 16 months postoperatively. Echocardiography showed that the residual shunt had also decreased in another 2 patients. CONCLUSIONS: We conclude that the sandwich technique is safe and easy. Even in cases with a residual shunt present, the shunt is expected to decrease as time passes. Further experience and longer follow-up of these patients are necessary to conclude whether this technique is applicable to neonates and young infants.

Blood Flow Velocity↗
PubMed2003

Intravesical resiniferatoxin for refractory detrusor hyperreflexia: a multicenter, blinded, randomized, placebo-controlled trial.

OBJECTIVE: Resiniferatoxin (RTX) is an analogue of capsaicin with more than 1,000 times its potency in desensitizing C-fiber bladder afferent neurons. This study investigated the safety and efficacy of intravesical RTX in patients with refractory detrusor hyperreflexia (DH). METHODS: Thirty-six (22 males, 14 females) neurologically impaired patients (20 spinal cord injury, 7 multiple sclerosis, 9 other neurologic diseases) with urodynamically verified DH and intractable urinary symptoms despite previous anticholinergic drug use were treated prospectively with intravesical RTX using dose escalation in a double-blind fashion at 4 centers. Patients received a single instillation of 100 mL of placebo (n = 8 patients) or 0.005, 0.025, 0.05, 0.10, 0.2, 0.5, or 1.0 microM of RTX (n = 4 each group). A visual analog pain scale (VAPS) (0-10; 10 = highest level of pain) was used to quantify discomfort of application. Treatment effect was monitored using a bladder diary and cystometric bladder capacity at weeks 1, 3, 6, and 12 posttreatment. RESULTS: Mean VAPS scores revealed minimal to mild discomfort with values of 2.85 and 2.28 for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. Due to the small sample size, there were no statistically significant changes in mean cystometric capacity (MCC) or incontinence episodes in each treatment dose group. However, at 3 weeks, MCC increased by 53% and 48% for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. Patients in the 0.5-microM and 1.0-microM groups with MCC < 300 mL at baseline showed greater improvements in MCC at 120.5% and 48%, respectively. In some patients, MCC increased up to 500% over baseline, despite a low RTX dose. Incontinence episodes decreased by 51.9% and 52.7% for the 0.5-microM and 1.0-microM RTX treatment groups, respectively. There were no long-term complications. CONCLUSION: Intravesical RTX administration, in general, is a well-tolerated new therapy for DH. This patient group was refractory to all previous oral pharmacologic therapy, yet some patients responded with significant improvement in bladder capacity and continence function shortly after RTX administration. Patients at risk for autonomic dysreflexia require careful monitoring during RTX therapy.

Administration, Intravesical↗
PubMed2003

Gene therapy for bladder pain with gene gun particle encoding pro-opiomelanocortin cDNA.

PURPOSE: Interstitial cystitis is a bladder hypersensitivity disease associated with bladder pain that has been a major challenge to understand and treat. We hypothesized that targeted and localized expression of endogenous opioid peptide in the bladder could be useful for the treatment of bladder pain. Pro-opiomelanocortin (POMC) is one of such precursor molecules. In this study we developed a gene gun method for the transfer of POMC cDNA in vivo and investigated its therapeutic effect on acetic acid induced bladder hyperactivity in rats. MATERIALS AND METHODS: Human POMC cDNA was cloned into a modified pCMV plasmid and delivered into the bladder wall of adult female rats by direct injection or the gene gun. Three days after gene therapy continuous cystometrograms were performed using urethane anesthesia by filling the bladder (0.08 ml per minute) with saline, followed by 0.3% acetic acid. Bladder immunohistochemical testing was used to detect endorphin after POMC cDNA transfer. RESULTS: The intercontraction interval was decreased after intravesical instillation of acetic acid (73.1% or 68.1% decrease) in 2 control groups treated with saline or the gene gun without POMC cDNA, respectively. However, rats that received POMC cDNA via the gene gun showed a significantly decreased response (intercontraction interval 35% decreased) to acetic acid instillation, whereas this antinociceptive effect was not detected in the plasmid POMC cDNA direct injection group. This effect induced by POMC gene gun treatment was reversed by intramuscular naloxone (1 mg/kg), an opioid antagonist. Increased endorphin immunoreactivity with anti-endorphin antibodies was observed in the bladder of gene gun treated animals. CONCLUSIONS: The POMC gene can be transferred in the bladder using the gene gun and increased bladder expression of endorphin can suppress nociceptive responses induced by bladder irritation. Thus, POMC gene gun delivery may be useful for the treatment of interstitial cystitis and other types of visceral pain.

Animals↗
PubMed2003

[New insights into neural mechanisms controlling the micturition reflex].

The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. This activity is in turn controlled by neural circuits in the brain, spinal cord, and peripheral ganglia. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. The brain rostral to the pons (diencephalon and cerebral cortex) is also involved in excitatory and inhibitory regulation of the micturition reflex. Various transmitters including dopamine, serotonin, norepinephrine, GABA, excitatory and inhibitory amino acids, opioids, acetylcholine, and neuropeptides are implicated in the modulation of the micturition reflex in the central nervous system. Therefore, injury or diseases of the nervous system, as well as drugs and disorders of the peripheral organs, can produce bladder and urethral dysfunctions such as urinary frequency, urgency and incontinence, or inefficient bladder emptying.

Central Nervous System↗
PubMed2003

Neurophysiology of lower urinary tract function and dysfunction.

With the continued aging of the population, the incidence of conditions associated with bladder control will continue to grow. In this article, we review the neurophysiology and pathophysiology of the bladder and urethra and discuss logical concepts for the development of novel drug therapy that can better help the expanding population of patients with bladder control problems.

Journal Article↗