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Biomedical subjects

William D Steers

Publications and source records attributed to William D Steers.

At least 19 recordsLinked to original sources
PubMed2006

Mechanisms of Disease: the role of nerve growth factor in the pathophysiology of bladder disorders.

The case is compelling for the involvement of nerve growth factor (NGF) in the pathogenesis of lower urinary tract disease, especially in conditions with altered neural function. Remodeling of the micturition pathways occurs following experimental bladder-outlet obstruction, denervation, spinal cord injury, cystitis, and diabetes mellitus. Clinically, NGF levels are elevated in the bladders of men with benign prostatic hyperplasia, women with interstitial cystitis and in patients with idiopathic overactive bladder. Blockade of NGF, using either an endogenous antibody or an antibody against the NGF receptor, prevents neural plasticity and bladder overactivity in experimental models of these conditions. The ability of NGF to trigger bladder overactivity might rely on altering the properties of sodium or potassium channels (or their expression) in bladder afferent fibers. Therapies based on altered NGF levels, or changes in channel properties in afferent nerves, represent an intriguing avenue of investigation for the management of detrusor overactivity or diabetic cystopathy.

Humans↗
PubMed2005

The role of corticotropin releasing factor and its antagonist, astressin, on micturition in the rat.

The purpose of this investigation was to evaluate the role of corticotropin releasing factor (CRF) on micturition. CRF is involved in the endocrine and central nervous system responses to stress and is also expressed in sites responsible for the control of micturition. In this investigation, cystometric experiments were performed in awake and unrestrained Wistar rats and on Spontaneous Hypertensive Rats, which are used as a rodent model of detrusor overactivity and anxiety. In vitro effects of CRF were evaluated using strips of detrusor muscle in an organ bath preparation. CRF (6.0 microg) administered via intrathecal and intraperitoneal routes, but not intracerebroventricularly, lowered the micturition threshold. CRF reduced the intercontraction interval by 28% and 26% after intrathecal or intraperitoneal administration, respectively, and reduced micturition volume by 34.7% and 30.2%, respectively. In Wistar-Kyoto rats, 6.0 microg intrathecal CRF significantly reduced intercontraction interval (423 +/- 79 vs. 669 +/- 59 s) and micturition volume (0.30 +/- 0.04 vs. 0.69 +/- 0.07 ml) compared to controls that received saline vehicle. These effects were blocked by pretreatment with 6.0 mug intrathecal astressin, a potent CRF antagonist, demonstrating that the effects are CRF receptor mediated. In Spontaneous Hypertensive Rats, 6.0 mug intrathecal CRF was found to have minimal stimulatory effects on the bladder, whereas astressin reduced baseline detrusor overactivity. CRF had no direct contractile effects on detrusor muscle strips. These results demonstrate that in the absence of detrusor overactivity, CRF stimulates micturition when administered via the intrathecal or intraperitoneal routes. Further studies are needed to explore the possibility whether CRF antagonists are effective for detrusor overactivity and the overactive bladder syndrome.

Animals↗
PubMed2004

Patient-centered goals for pelvic floor dysfunction surgery: long-term follow-up.

OBJECTIVE: This study was undertaken to describe long-term postoperative perceived achievement of subjective preoperative goals for pelvic floor dysfunction (PFD) surgery. STUDY DESIGN: From March 2000 through December 2001, 123 PFD surgical patients completed a preoperative open-ended questionnaire on which they described up to 5 personal outcome goals for PFD surgery. Patients were asked to review their original goals list and assess the degree to which they had met their goals on a 5-point scale (-2=strongly disagree the goal had been met to +2=strongly agree that the goal had been met) 3 months after surgery and again between 1 and 3 years after surgery. At the second follow-up, patients also completed the Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) instruments to assess life impact and symptom distress, respectively. RESULTS: Of 50 women to date with long-term follow-up, 98% were white, 96% had delivered at least 1 child, 38% had previous surgery for PFD, mean weight was 74.2 +/- 14.1 kilos, and mean age was 65.4 +/- 11.5 years. Mean follow-up duration was 1.8 years, and ranged from 0.98 to 3.01 years. Of 194 goals listed by participants, 40.2% had to do with resuming previous activities or lifestyle, 38.1% with symptom relief, 9.3% with improving self-image and social relationships, 7.7% with improving general health, and 4.6% with improving physical appearance. At the individual goal level, 72% of goals were attained at short-term, and 68% attained at long-term follow-up. Long-term goal achievement did not vary significantly by category of goal. Goal achievement was lower only for symptom relief at long-term follow-up (68.9%) than at short-term follow-up (87.4%, P <.001). At the person level, 45.8% of women reported achieving all listed goals in the short term, and 42.0% in the long term. Long-term goal achievement was associated with PFD-specific quality of life (UDI-6 and IIQ-7 scores) and inversely associated with surgical complications, but was not associated with other clinical or demographic variables, including weight, parity, PFD diagnosis, psychiatric comorbidity, surgical route, or previous surgical history. CONCLUSION: Self-reported achievement of preoperatively recorded goals for PFD surgery persisted 1 to 3 years after surgery. The association of goal achievement to IIQ-7 and UDI-6 scores suggests that goal achievement is related to, but not identical to, overall measures of PFD life impact and symptom distress. Future work should examine the association of goal achievement to clinical measures of PFD severity, and compare surgically and medically managed patients. Preoperative assessment of goals may be a useful addition to clinical and subjective data in the long-term management of women with pelvic floor disorders.

Aged↗
PubMed2004

Establishing a robotics program.

Establishing a successful robotics program requires consideration of several issues, including the surgical procedures to be performed, training and personnel, facilities, finance, and marketing. This article considers these factors from an academic health center standpoint and evaluates the benefits and risks of this new technology for urology departments.

Health Facilities↗
PubMed2004

Corticotropin releasing factor: a mediator of emotional influences on bladder function.

PURPOSE: We review evidence linking overactive bladder (OAB) and interstitial cystitis with anxiety and depression, and highlight the importance of corticotropin releasing factor (CRF) as a potential mediator of these conditions. MATERIALS AND METHODS: We review the literature and describe ongoing experiments. RESULTS: CRF is expressed in areas of the central nervous system that control voiding and response to stress. CRF is increased during anxiety, depression and pain as well as functional disorders of the pelvic viscera. Epidemiological studies reveal an association between anxiety and voiding disorders. Experiments in our laboratory show that CRF stimulates bladder activity while CRF antagonists inhibit OAB. CONCLUSIONS: Epidemiological, genetic and neuropharmacological evidence links disorders of voiding and anxiety. CRF may participate in these events and warrants further investigation as a therapeutic target in the treatment of OAB and interstitial cystitis.

Animals↗
PubMed2003

Viability and safety of combination drug therapies for erectile dysfunction.

PURPOSE: In some patients with erectile dysfunction (ED) oral, topical or intracavernous drug therapy fails. However, several classes of drugs demonstrate efficacy for ED, creating the potential for pharmacological combinations preferable to implantation of a penile prosthesis. MATERIALS AND METHODS: Preliminary reports suggest that combining oral, topical or intracavernous drugs may salvage patients in whom monotherapy fails. RESULTS: Agents that lead to activation or increases in cyclic nucleotides (cyclic adenosine monophosphate and guanosine monophosphate) with or without nitric oxide donors or nitrates, or alpha-adrenergic antagonists have been used to treat ED. The phosphodiesterase-5 inhibitor sildenafil has been combined with alprostadil (prostaglandin E1) and administered by either the intraurethral or intracavernous route. Successful intercourse following this combination varies from 47% to 100% when monotherapy with each has failed. The introduction of apomorphine has led to its unapproved use in combination with sildenafil in Europe. Combination strategies may allow lower drug doses and reduced adverse effects. CONCLUSIONS: The encouraging preliminary observations combined with the potential for adverse events provide a scientific rationale for prospective, randomized clinical trials with adequate numbers of subjects.

Alprostadil↗
PubMed2003

Alterations in voiding frequency and cystometry in the clomipramine induced model of endogenous depression and reversal with fluoxetine.

PURPOSE: Because serotonin (5-HT) in the central nervous system may inhibit bladder activity, we postulated that depression associated with altered 5-HT function might be associated with overactive bladder (OAB). We examined a rat model of endogenous depression caused by lowering 5-HT for effects on voiding frequency (VF) and awake cystometry (CMG), and examined the effect of reversal using the selective serotonin reuptake inhibitor fluoxetine. MATERIALS AND METHODS: Wistar rat pups were divided into 2 groups, namely clomipramine treated (CL) and saline control (SC). From postnatal days 8 to 21 each pup was injected with CL hydrochloride (22.5 mg/kg body weight) or an equal volume of saline. VF was assessed at 10 and 15 weeks. Behavioral correlates of depression were assessed using the forced swim test. At age 15 weeks CMG was performed. Fluoxetine (20 mg/kg daily) was administrated to a subset of SC/CL rats, and VF and CMG were repeated. RESULTS: In CL rats immobility was increased when rats were submitted to the forced swim test, indicating depression. CL rats voided more frequently than the SC group at 10 and 15 weeks but the difference was significant only in females. CMG of female CL group showed decreased bladder capacity, micturition volume and intermicturition contractions compared with the SC group. Treatment with fluoxetine reversed these changes, as in SC rats. CONCLUSIONS: These results support the hypothesis that OAB in a subgroup of depressed individuals may be associated with altered 5-HT function. It may explain reports of an association between depression and OAB.

Animals↗
PubMed2002

RhoA-mediated Ca2+ sensitization in erectile function.

A Rho-kinase inhibitor increases corpus cavernosum (CC) pressure in an in vivo rat model (Chitaley, K., Wingard, C. J., Webb, R. C., Branam, H., Stopper, V. S., Lewis, R. W., and Mills, T. M. (2001) Nat. Med. 7, 119-122) suggesting that Rho-mediated Ca(2+) sensitization of CC smooth muscle maintains the flaccid (contracted) state. We directly demonstrate Ca(2+) sensitization of permeabilized rabbit and human CC and identify a highly expressed molecular component of this pathway. Ca(2+) sensitization of force induced by endothelin or GTPgammaS was significantly greater in CC than in rabbit ileum smooth muscle and was accompanied by a 17-fold higher RhoA content. Pull-down assays with the RhoA binding domain of mDia showed the high RhoA content of CC to be available for activation by GTPgammaS. Ca(2+) sensitization induced by endothelin, phenylephrine, or GTPgammaS was completely relaxed by the Rho kinase inhibitor Y-27632. Human and rabbit CC both express the phosphatase inhibitor CPI-17, the myosin phosphatase regulatory (MYPT-1) and catalytic (PP1delta) subunits, and two isoforms of Rho kinase. We suggest that high expression of RhoA contributes, through RhoA-mediated Ca(2+) sensitization, to the flaccid state of CC that can be reversed by a water-soluble, orally active Rho kinase inhibitor suitable for therapy of erectile dysfunction.

Animals↗
PubMed2002

Patient-centered goals for pelvic floor dysfunction surgery: what is success, and is it achieved?

OBJECTIVE: The purpose of this study was to describe patient-identified goals for pelvic floor dysfunction surgical procedures and patient-reported achievement of those goals. STUDY DESIGN: Thirty-three consecutive patients scheduled for pelvic floor dysfunction surgical procedures completed a preoperative questionnaire on which they listed up to 5 personal goals for surgical outcomes. At 6- and 12-week follow-up, patients reported the degree (rated 1-5) to which each goal had been met (1 = strongly disagree that the goal was met; 5 = strongly agree). Age, race, vaginal parity, previous pelvic surgical procedures, pelvic floor dysfunction diagnosis, pelvic floor dysfunction surgical procedure, and perioperative complications were also recorded. Goals were categorized as being primarily related to symptom relief, increasing activity, general or other health concerns, social relationships and self-image, or physical appearance. Rates of self-reported goal achievement at 6 and 12 weeks were calculated, and differences in the proportion of goals achieved by category were assessed. RESULTS: Women reported a mean of 3.6 goals; 24 of 33 women (72.7%) listed > or = 4 goals. Of the 119 goals listed, 51 goals (42.9%) dealt with urinary or bowel symptoms; 36 goals (30.3%) dealt with improving activity; 15 goals (12.6%) dealt with general health concerns; 14 goals (11.8%) dealt with social relationships and self-image, and 3 goals (2.5%) dealt with physical appearance. Twenty-seven of the 33 women (81.8%) listed symptom relief; 22 women (66.7%) listed at least 1 activity-related goal; 14 women (42.4%) listed general or longer term health, and 11 women (33.3%) listed a social or self-image goal. Of the 119 goals listed, women agreed or strongly agreed that 88 goals (73.9%) were met at 6 weeks, and 101 goals (84.9%) were met at 12 weeks (chi(2) = 3.7 for difference between proportion at 6 and 12 weeks; P =.054). At 6 weeks, women agreed or strongly agreed that most goals had been met for activity, symptoms, general health, and appearance, but not for social/self-image goals (chi(2) = 24.9; P <.001). However, by 12 weeks, women agreed or strongly agreed that most goals had been met in all categories. CONCLUSION: Women who undergo pelvic floor dysfunction surgical procedures have a variety of desired subjective outcomes. Goals that relate to social roles, sexuality, and self-image may take longer to successfully achieve than other types of goals. Longer-term follow-up is crucial to determine whether initial improvements have been maintained. Assessment of patient goals is quick and easy and may help clinicians better understand and care for their patients.

Adult↗