Bio

Academic Appointments


Professional Education


  • FRCSI, Royal Coll Surgeons Irel, Surgery (1989)
  • BSc(Hons), National University of Ireland, Anatomy & Embryology (1986)
  • MB, BCh, BAO, National University of Ireland, Medicine (1984)
  • LRCPI&SI, Royal Coll Surgeons In Ireland, Medicine (1984)

Research & Scholarship

Current Research and Scholarly Interests


My research interests are clinically 1) voiding dysfunction (BPH, incontinence, urinary retention, & neurogenic bladder). 2) Outcomes research and am currently developing a project to review the management of neurogenic bladder within the VA.
Prior research in this field is in BPH.

My Basic science interests are in epithelial physiology particularly that of the urothelium lining the bladder. Specifically permeability properties and neuro-epithelial interactions relating to sensation

Teaching

2013-14 Courses


Publications

Journal Articles


  • Incontinence related to management of benign prostatic hypertrophy. American journal of geriatric pharmacotherapy Han, E., Black, L. K., Lavelle, J. P. 2007; 5 (4): 324-334

    Abstract

    The prevalence of incontinence ranges from 11% to 34% among community-dwelling men aged > or =65 years.The objective of this analysis was to determine the nature of incontinence diagnosed in men with benign prostatic hypertrophy (BPH), focusing on its incidence, prevalence, diagnostic workup, and management.A cohort of patients with BPH was identified in the Integrated Healthcare Information Services National Managed Care Benchmark Database (1997-2003). Age and duration in the database after the first diagnosis of BPH were used as matching strata. Therapeutic subgroups consisted of watchful waiting, alpha-blockers, 5-alpha-reductase inhibitors (5ARIs), and BPH-related surgery.A total of 411,658 males with BPH were identified from 12,298,027 males (3.3%). Of the BPH cohort, 2.7% (n = 11,172) were identified as having incontinence; of these, 57.8% of patients were > or =65 years of age. Alter applying inclusion/exclusion criteria, the final matched case-control sample included 6346 men as case subjects and 229,154 men as control subjects. The overall incidence of incontinence in this BPH sample was 1835/100,000/year, and the prevalence was 2713/100,000 men. In 48.5% of the incontinent men, the type of incontinence was not specified. Diagnostic testing was performed in 2.9% of men with incontinence. Conditional logistic regression analyses found that BPH-related surgery and alpha-blocker use increased the adjusted odds ratio for the risk of incontinence 3.1-fold, and 1.1- to 1.7-fold, respectively. The odds ratio of the risk of incontinence was not significantly increased with long-term 5ARI use.Use of alpha-blockers, 5ARIs for the short term (<1 year), and BPH-related surgery were independently, significantly associated with BPH-related incontinence; 5ARI use for >1 year and watchful waiting were not. BPH-related incontinence may be related to progression of BPH or as a postsurgical complication. Patients with BPH should be asked specifically about incontinence, especially after BPH-related surgery, and undergo a full diagnostic workup for the diagnosis of urinary incontinence.

    View details for DOI 10.1016/j.amjopharm.2007.12.003

    View details for PubMedID 18179990

  • An evaluation of the economic costs and patient-related consequences of treatments for benign prostatic hyperplasia BJU INTERNATIONAL Disantostefano, R. L., Biddle, A. K., Lavelle, J. P. 2006; 97 (5): 1007-1016

    Abstract

    To compare the costs and effectiveness of treatments for benign prostatic hyperplasia (BPH), including watchful waiting, pharmaceuticals (alpha-blockers, 5-alpha-reductase inhibitors, combined therapy), transurethral microwave thermotherapy (TUMT), and transurethral resection of the prostate (TURP).This study used a Markov model over a 20-year period and the societal perspective to evaluate the costs of treatment alternatives for BPH. Markov states include urinary symptom improvement, symptom improvement with adverse effects, or no urinary symptom improvement. For the analysis, patients could remain on their initial treatment, change to a different treatment, have treatment failure that required TURP, or die (all-cause mortality). We used published data for outcomes, including systematic reviews when possible. Costs were estimated using a managed-care claims database and Medicare fee schedules. Costs and effectiveness outcomes were discounted at 3%/year where appropriate. Men (aged > or = 45 years) with moderate-to-severe lower urinary tract symptoms and uncomplicated BPH were included in the analysis, and results were stratified by age. Outcomes include costs, disease progression, surgery, hospitalization, and catheterization time.What is the 'best' treatment depends on the value that an individual and society place on costs and consequences. alpha-Blockers are less expensive than the alternatives, and are effective at relieving patient-reported symptoms. Unfortunately, they have little effect on clinical outcomes and have the highest BPH progression rate. Other treatments have lower disease progression and better clinical outcomes, but are more expensive and entail more invasive treatments, and/or more uncertainty.Treatment decisions are made using a variety of information, including the cost and consequences of treatment. The best treatment depends on the patient's preference and the outcome considered most important. alpha-Blockers are very effective at treating urinary symptoms but do not improve clinical outcomes, including disease progression, relative to other treatments. TURP remains the 'gold standard' for surgical procedures. The desire to avoid TURP or the 2 weeks of catheterization associated with TUMT might affect a patient's treatment decision when symptoms are severe. Therefore, more information about patient preferences and risk aversion is needed to inform treatment decision-making for BPH.

    View details for DOI 10.1111/j.1464-410X.2006.06089.x

    View details for Web of Science ID 000237558400024

    View details for PubMedID 16542339

  • The economic impact of prostate cancer screening and treatment. North Carolina medical journal DiSantostefano, R. L., Lavelle, J. P. 2006; 67 (2): 158-160

    View details for PubMedID 16752723

  • Management of incontinence for family practice physicians AMERICAN JOURNAL OF MEDICINE Lavelle, J. P., Karrarn, M., Dmochowski, R., MacDiarmid, S. A., Staskin, D. R., Sand, P. K., Appell, R., Erdern, N. 2006; 119: 37-40

    Abstract

    Family practice physicians are likely to encounter urinary incontinence and overactive bladder (OAB) in their patients. An informed family practice physician can generally accurately diagnose the cause and type of incontinence in patients with a properly focused physical examination and, if necessary, auxiliary testing. Accurate diagnosis can lead to effective treatment when physicians are familiar with available treatment options, including pharmacologic, surgical, behavioral therapies, and catheterization.

    View details for DOI 10.1016/j.amjmed.2005.12.015

    View details for Web of Science ID 000235908700007

    View details for PubMedID 16483867

  • The long-term cost effectiveness of treatments for benign prostatic hyperplasia PHARMACOECONOMICS Disantostefano, R. L., Biddle, A. K., Lavelle, J. P. 2006; 24 (2): 171-191

    Abstract

    Excellent treatment outcomes with long-term durability and few adverse effects are expectations of treatments for chronic conditions. The long-term cost effectiveness of newer treatments for benign prostatic hyperplasia (BPH), including high-energy transurethral microwave thermotherapy (TUMT) and combination pharmaceutical therapy, has not been sufficiently studied against existing alternatives. The objective of this study was to estimate the incremental cost effectiveness of BPH treatment alternatives.We employed a Markov model over a 20-year time horizon and the payer's perspective to evaluate the cost effectiveness of watchful waiting (WW), pharmaceuticals (alpha-adrenoceptor antagonists [alpha-blockers], 5-alpha-reductase inhibitors [5-ARIs], combination therapy), TUMT and transurethral resection of the prostate (TURP) in treating BPH. Markov states included improvement in symptoms, no improvement in symptoms, adverse effects and death. We used data from the published literature for outcomes, including systematic reviews whenever possible. Costs were estimated using a managed-care claims database and Medicare fee schedules, and were reported in Dollars US, 2004 values. Costs and effectiveness outcomes were discounted at a rate of 3% per year. Men (aged > or =45 years) with moderate to severe lower urinary tract symptoms and uncomplicated BPH were included in the analysis, and results were stratified by age and BPH symptom levels. Outcomes included costs, QALYs, incremental cost-utility ratios and cost-effectiveness acceptability curves. Sensitivity analysis was performed on important parameters, with an emphasis on probabilistic sensitivity analysis.alpha-Blockers and TUMT were cost effective for treating moderate symptoms using the threshold of Dollars US 50,000 per QALY. For example, at 65 years of age, the cost per QALY was Dollars US 16,018 for alpha-blockers compared with WW and Dollars US 30,204 for TUMT versus alpha-blockers. TURP was the most cost-effective treatment for severe symptoms (Dollars US 5824 per QALY ) versus WW. Model results were robust to changes in costs and sensitive to the assumed probabilities, utility weights, extent of improvement and life expectancy. Nevertheless, acceptability curves consistently demonstrated the same alternatives as most likely to be cost effective.Our model suggests that alpha-blockers and TURP appear to be the most cost-effective alternatives, from a US payer perspective, for BPH patients with moderate and severe symptoms, respectively. TUMT was promising for patients with moderate symptoms and the oldest patients with severe symptoms, but otherwise was dominated. Value of information analysis could be used to determine the net benefit of additional research.

    View details for Web of Science ID 000236163100006

    View details for PubMedID 16460137

  • Rare cause of ureteral obstruction. Urology Gaston, K. E., Gabriel, D. A., Lavelle, J. P. 2005; 66 (5): 1110-?

    Abstract

    This report presents bilateral ureteral obstruction due to possible ureteritis in a bone marrow transplant patient with resurgence of BK virus after hemorrhagic cystitis. This is believed to be the first description of this type of ureteral obstruction. The presented case includes the management plan.

    View details for PubMedID 16286146

  • Plasma cell (Zoon's) balanitis with concomitant HIV infection UROLOGY Houser, E. R., Gaston, K. E., Funkhouser, W. K., Israel, B., Lavelle, J. P. 2005; 66 (3): 657E13-657E14
  • Plasma cell (Zoon's) balanitis with concomitant HIV infection. Urology Houser, E. R., Gaston, K. E., Funkhouser, W. K., Israel, B., Lavelle, J. P. 2005; 66 (3): 657-?

    Abstract

    We report a case of the development of Zoon's balanitis in an African-American man with human immunodeficiency virus. Photographs of the clinical and pathological lesion are presented. To our knowledge, this has not been recently reported in urologic studies. The clinicopathologic correlation is discussed.

    View details for PubMedID 16140101

  • Re: an economic evaluation of doxazosin, finasteride and combination therapy in the treatment of benign prostatic hyperplasia. Canadian journal of urology Disantostefano, R. L., Biddle, A. K., Lavelle, J. P. 2005; 12 (1): 2508-2509

    View details for PubMedID 15777487

  • Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity UROLOGY Chuang, Y. C., Chancellor, M. B., Seki, S., Yoshimura, N., Tyagi, P., Huang, L., Lavelle, J. P., de Groat, W. C., Fraser, M. O. 2003; 61 (3): 664-670

    Abstract

    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).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.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.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.

    View details for DOI 10.1016/S0090-4295(02)02280-X

    View details for Web of Science ID 000181928200041

    View details for PubMedID 12639680

  • Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Kanai, A. J., Zeidel, M. L., Lavelle, J. P., Greenberger, J. S., Birder, L. A., de Groat, W. C., Apodaca, G. L., Meyers, S. A., Ramage, R., Epperly, M. W. 2002; 283 (6): F1304-F1312

    Abstract

    Urinary bladder cystitis occurs in patients receiving radiation therapy for pelvic tumors. Radiation-induced formation of superoxide radicals is believed to damage the urothelium, exposing the underlying bladder smooth muscle to urine, culminating in nerve irritation and muscle dysfunction. We tested whether overexpression of MnSOD could decrease superoxide levels and protect the bladder from radiation damage. Pelvic irradiation led to sloughing of urothelial umbrella cells, with decreased transepithelial resistance, increased water and urea permeabilities, and increased expression of inducible nitric oxide synthase. Six months after irradiation, cystometrograms showed elevated intravesical pressures and prolonged voiding patterns. However, urothelia transfected with the MnSOD transgene recovered from radiation injury more rapidly, and detrusor function was much closer to that of control bladders than irradiated bladders without the transgene. We conclude that MnSOD gene therapy is protective, which could lead to its use in mitigating radiation cystitis and preventing dysfunction of the urinary bladder.

    View details for DOI 10.1152/ajprenal.00228.2002

    View details for Web of Science ID 000179106600014

    View details for PubMedID 12426235

  • The future of bladder control-intravesical drug delivery, a pinch of pepper, and gene therapy. Reviews in urology Fraser, M. O., Lavelle, J. P., Sacks, M. S., Chancellor, M. B. 2002; 4 (1): 1-11

    Abstract

    The incidence of urinary incontinence and overactive bladder problems will continue to grow as the population ages. Future treatments are likely to include an implantable drug delivery system, gene therapy, and the intravesical use of the vallinoids capsaicin and resiniferatoxin (RTX). An understanding of the urothelium is essential for effective design of these therapies. Intravesical anticholinergic drug treatment is currently not widely used, but intravesical pumps are under development to provide less cumbersome treatment methods and will provide nonsurgical options for patients who cannot tolerate oral anticholinergic agents. Research on the use of capsaicin as an intravesicular drug has had limited success, but trials have confirmed the efficacy of intravesical capsaicin for detrusor hyperreflexia. RTX is as effective as capsaicin but without side effects, such as pain and inflammatory neuropeptide release. RTX treatment may eliminate the need for surgical and other drug treatments of lower urinary tract dysfunction in patients with spinal cord injuries. Gene therapy will change the practice of urology by addressing the deficiencies that cause symptoms rather than attacking the symptoms themselves.

    View details for PubMedID 16985646

  • Detection of tumorigenesis in rat bladders with optical coherence tomography MEDICAL PHYSICS Pan, Y. T., Lavelle, J. P., Bastacky, S. I., Meyers, S., Pirtskhalaishvili, G., Zeidel, M. L., Farkas, D. L. 2001; 28 (12): 2432-2440

    Abstract

    Optical coherence tomography (OCT) is a novel technique that enables noninvasive cross-sectional imaging of biological tissues. Because of its high resolution (approximately 10 microm), superior dynamic range (140 dB in our case) and up to 2-3 mm penetration depth, OCT is potentially useful for noninvasive screening of superficial lesions. Bladder cancer arises within the transitional epithelium. Despite the ability to visualize the epithelium via cystoscopy, it is often difficult to detect early epithelial cancers and to determine their penetration to the underlying layers. To investigate the potential of OCT to enhance imaging of bladder cancers and other epithelial lesions, we applied OCT to normal and diseased bladder epithelium, and correlated the results with histological findings. OCT images of porcine bladder (a close homolog of human bladder) confirm the ability of this method to image human tissues. To determine whether OCT can track the course of bladder cancer, a standard rat model of bladder cancer in which Fisher rats are exposed to methyl-nitroso-urea (MNU), was followed both with OCT and histological studies. Our results show that the micro morphology of porcine bladder such as the urothelium, submucosa and muscles is identified by OCT and well correlated with the histological evaluations. OCT detected edema, inflammatory infiltrates, and submucosal blood congestion as well as the abnormal growth of urothelium (e.g., papillary hyperplasia and carcinomas). By contrast, surface imaging, which resembles cystoscopy, provided far less sensitivity and resolution than OCT. This is the first OCT study of any tumor documented in a systematic fashion, and the results suggest the potential of OCT for the noninvasive diagnosis of both bladder inflammatory lesions and early urothelial abnormalities, which conventional cystoscopy often misses, by imaging characterization of the increases in urothelial thickening and backscattering. However, because of the depth limitation, OCT may have limited applications in staging the invasion of higher-state urothelial cancers, especially for papillary carcinomas.

    View details for DOI 10.1118/1.1418726

    View details for Web of Science ID 000172896200007

    View details for PubMedID 11797946

  • Permeability of intestinal mucosa from urinary reservoirs in man and rat BJU INTERNATIONAL Lavelle, J. P., Rea, D. R. 2001; 88 (4): 444-444

    View details for Web of Science ID 000170905700032

    View details for PubMedID 11564041

  • A reliable, nondestructive animal model for interstitial cystitis: intravesical low-dose protamine sulfate combined with physiological concentrations of potassium chloride. Urology Fraser, M. O., Chuang, Y. C., Lavelle, J. P., Yoshimura, N., de Groat, W. C., Chancellor, M. B. 2001; 57 (6): 112-?

    View details for PubMedID 11378082

  • Botulinum toxin urethral sphincter injection to restore bladder emptying in men and women with voiding dysfunction JOURNAL OF UROLOGY Phelan, M. W., Franks, M., Somogyi, G. T., Yokoyama, T., Fraser, M. O., Lavelle, J. P., Yoshimura, N., Chancellor, M. B. 2001; 165 (4): 1107-1110

    Abstract

    Botulinum toxin injection into the external urinary sphincter in spinal cord injured men with detrusor-sphincter dyssynergia has been reported. We expand the clinical use of botulinum toxin for a variety of bladder outlet obstructions and to decrease outlet resistance in patients with acontractile detrusor but who wish to void by the Valsalva maneuver.Prospective treatment was performed for voiding dysfunction in 8 men and 13 women 34 to 74 years old. The reasons for voiding dysfunction included neurogenic detrusor-sphincter dyssynergia in 12 cases, pelvic floor spasticity in 8 and acontractile detrusor in 1 patient with multiple sclerosis who wished to void by the Valsalva maneuver. Using a rigid cystoscope and a collagen injection needle, a total of 80 to 100 units of botulinum A toxin (Botox) were injected into the external sphincter at the 3, 6, 9 and 12 o'clock positions.Preoperatively 19 of 21 patients were on indwelling or intermittent catheterization. After botulinum A injection all but 1 patient were able to void without catheterization. No acute complications, such as general paralysis or respiratory depression, occurred and none of the patients had dribbling or stress urinary incontinence. Postoperative post-void residual decreased by 71% and voiding pressures decreased on average 38%. Of the 21 patients 14 (67%) reported significant subjective improvement in voiding. Followup ranges from 3 to 16 months, with a maximum of 3 botulinum A injections in some patients.Urethral sphincter botulinum injection should be considered for complex voiding dysfunction. Encouraging improvement without complications were seen in most of our patients. We have expanded the use of botulinum toxin to treat pelvic floor spasticity and also women.

    View details for Web of Science ID 000167503700011

    View details for PubMedID 11257648

  • Effects of vitamin D (calcitriol) on transitional cell carcinoma of the bladder in vitro and in vivo JOURNAL OF UROLOGY Konety, B. R., Lavelle, J. P., Pirtskalaishvili, G., Dhir, R., Meyers, S. A., Nguyen, T. S., Hershberger, P., Shurin, M. R., Johnson, C. S., Trump, D. L., Zeidel, M. L., Getzenberg, R. H. 2001; 165 (1): 253-258

    Abstract

    Vitamin D (calcitriol) has significant antiproliferative effects on various tumor cells in vitro and in vivo. In the clinical situation a major impediment to systemic administration of calcitriol is the side effect of hypercalcemia. To test the potential usefulness of calcitriol for bladder cancer treatment, we studied the antiproliferative effect of vitamin D on 2 human bladder cancer cell lines, 253j and T-24, in vitro. We also examined the in vivo effects of calcitriol in an animal model of bladder cancer using intravesical administration to avoid the toxicity of systemic calcitriol therapy.The presence of vitamin D receptors in normal and neoplastic human bladder tissue, and tumor cells T-24 and 253j was determined by immunoblot analysis. Tumor cell proliferation in the presence or absence of calcitriol was determined using a crystal violet assay. Calcitriol induced apoptosis was determined by morphology, polyadenosine diphosphate ribose polymerase cleavage and annexin V binding. In vivo studies were performed by weekly intravesical instillation of calcitriol in female Fischer 344 rats after induction of tumors by N-methyl nitrosourea. Calcitriol administration was started 3 weeks after tumor induction for 7 doses at weekly intervals.Normal and neoplastic human bladder tissue, and the cell lines expressed vitamin D receptors. In the 253j and T-24 cell lines proliferation was significantly inhibited by calcitriol. Progressive cleavage of full length polyadenosine diphosphate ribose polymerase was observed in calcitriol treated cells starting as early as 4 hours after exposure. Similar changes were not observed in the control cells treated with vehicle (ethanol) alone. After 24 hours of treatment with calcitriol 45.8% of 253j cells bound annexin compared to 16.5% of control cells (chi-square p <0.001). Of the control animals 66% developed bladder tumors and 55% of the animals treated with calcitriol early (3 weeks) after tumor induction developed bladder tumors. Almost all of the tumors that developed in the calcitriol group were unifocal, and only 20% were invasive compared to 50% of those in the control animals.These results demonstrate that calcitriol inhibits proliferation and induces apoptosis in human bladder tumor cells in vitro, and may have therapeutic potential in bladder cancer. In vivo studies using an N-methylnitrosourea induced model of bladder cancer demonstrate that early institution of intravesical calcitriol therapy after carcinogen exposure results in fewer tumors, which are also less likely to be multifocal, high grade or invasive. With our protocol a short course of intravesical calcitriol administration did not result in any significant toxicity.

    View details for Web of Science ID 000165756300082

    View details for PubMedID 11125420

  • Metastatic osteomyelitis after pubovaginal sling using bone anchors. Urology Franks, M. E., Lavelle, J. P., Yokoyama, T., Chuang, Y. C., Chancellor, M. B. 2000; 56 (2): 330-331

    Abstract

    We report a case of osteomyelitis with metastasis to the T10 vertebra related to bone anchor use with pubovaginal sling. The morbidity was significant: long-term intravenous antibiotics, multiple surgeries to correct the problem, and subsequent chronic pelvic pain. Given that this complication is unheard of after standard fascia or allograft sling, consideration should be given before bone anchor use in women at risk for wound infection (diabetes, obesity, or reoperation). Minimally, patients should be told of the possibility of this severe complication in the informed consent with bone anchor use.

    View details for PubMedID 10925111

  • Urothelial pathophysiological changes in feline interstitial cystitis: a human model AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Lavelle, J. P., Meyers, S. A., Ruiz, W. G., Buffington, C. A., Zeidel, M. L., Apodaca, G. 2000; 278 (4): F540-F553

    Abstract

    Unique barrier properties of the urothelial surface membrane permit urine storage. Interstitial cystitis causes disabling dysuria, and frequency. Similarly, feline interstitial cystitis (FIC) occurs in cats. These studies define the permeability and structural properties of normal and FIC urothelium. To determine the effects of bladder filling, groups were studied before and after hydrodistention. Normal urothelium with or without hydrodistention exhibited high transepithelial resistances (TER) and low water and urea permeabilities, resembling other species. Fluorescence confocal microscopy revealed localization of the marker AE-31 to the apical surface of all umbrella cells in normal urothelium, with the tight junction protein ZO-1 localized to tight junctions. Scanning and transmission electron microscopy revealed uniform distribution of luminal cells with characteristic apical membrane and tight junction morphology. Urothelium in FIC animals displayed reduced TER and increased water and urea permeability following hydrodistention. Structural studies in FIC revealed denuded urothelium, with appearance of AE-31 in underlying epithelial cells. The results demonstrate severe epithelial damage and dysfunction in FIC and suggest novel approaches toward examining the etiology and therapy of IC.

    View details for Web of Science ID 000086457800004

    View details for PubMedID 10751214

  • Medical and minimally invasive treatment of urinary incontinence. Reviews in urology Lavelle, J. P., Teahan, S., Kim, D. Y., Chancellor, M. B. 1999; 1 (2): 111-119

    Abstract

    Newer agents and procedures give urologists more options in treating patients who have urinary incontinence related to such etiologies as an ineffective sphincter, detrusor hypersensitivity, obstruction, or a combination of these. Abolition of the involuntary contractions characteristic of detrusor instability can be accomplished pharmacologically or surgically. First-line anticholinergic agents are tolterodine and oxybutynin XL, given orally. Alternatively, intravesical administration provides a high concentration of drug, such as capsaicin or resiniferatoxin, at the detrusor muscle level. However, this commits the patient to intermittent self-catheterization. Surgery is reserved for those who have failed prolonged trials of conservative therapies. For patients with intractable urge incontinence, urologists have the new technique of sacral nerve stimulation.

    View details for PubMedID 16985783

  • Disruption of guinea pig urinary bladder permeability barrier in noninfectious cystitis AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Lavelle, J. P., Apodaca, G., Meyers, S. A., Ruiz, W. G., Zeidel, M. L. 1998; 274 (1): F205-F214

    Abstract

    Although most cell membranes permit rapid flux of water, small nonelectrolytes, and ammonia, the apical membranes of bladder epithelial umbrella cells, which form the bladder permeability barrier, exhibit strikingly low permeabilities to these substances. In cystitis, disruption of the bladder permeability barrier may irritate the bladder wall layers underlying the epithelium, causing or exacerbating inflammation, and increasing urinary frequency, urgency, and bladder pain. To determine the effects of inflammation on the integrity of the permeability barrier, guinea pigs were sensitized with ovalbumin, and the bladders were exposed subsequently to antigen by instillation on the urinary side. Inflammation of the bladder wall markedly reduced transepithelial resistance of dissected epithelium mounted in Ussing chambers and increased water and urea permeabilities modestly at 2 h and more strikingly at 24 h after induction of the inflammation. Transmission and scanning electron microscopy of bladders at 30 min and 24 h after antigen exposure revealed disruption of tight junctions, denuding of patches of epithelium, and occasional loss of apical membrane architecture. These permeability and structural effects did not occur in nonsensitized animals in which the bladders were exposed to antigen and in sensitized animals exposed to saline vehicle rather than antigen. These results demonstrate that inflammation of the underlying muscle and lamina propria can disrupt the bladder permeability barrier by damaging tight junctions and apical membranes and causing sloughing of epithelial cells. Leakage of urinary constituents through the damaged epithelium may then exacerbate the inflammation in the underlying muscle layers.

    View details for Web of Science ID 000071504900025

    View details for PubMedID 9458841

  • Benign fibroepithelial polyps causing symptomatic bilateral intermittent hydroureteronephrosis JOURNAL OF UROLOGY Lavelle, J. P., Knisely, A. S., Bellinger, M. F. 1997; 158 (2): 569-569

    View details for Web of Science ID A1997XL14300085

    View details for PubMedID 9224362

  • Low permeabilities of MDCK cell monolayers: A model barrier epithelium AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Lavelle, J. P., Negrete, H. O., Poland, P. A., Kinlough, C. L., Meyers, S. D., Hughey, R. P., Zeidel, M. L. 1997; 273 (1): F67-F75

    Abstract

    Barrier epithelia such as the renal collecting duct (in the absence of antidiuretic hormone) and thick ascending limb, as well as the stomach and mammalian bladder, exhibit extremely low permeabilities to water and small nonelectrolytes. A cell culture model of such epithelia is needed to determine how the structure of barrier apical membranes reduce permeability and how such membranes may be generated and maintained. In the present studies, the transepithelial electrical resistance and isotopic water and urea fluxes were measured for Madin-Darby canine kidney (MDCK) type I and type II cells, as well as type I cells expressing the mucin protein, MUC1, in their apical membranes. Although earlier studies had found the unstirred layer effects too great to permit measurement of transepithelial permeabilities, use of ultrathin semipermeable supports in this study overcame this difficulty. Apical membrane diffusive water permeabilities were 1.8 +/- 0.4 x 10(-4) cm/s and 3.5 +/- 0.5 x 10(-4) cm/s in MDCK type I and type II cells, respectively, at 20 degrees C. Urea permeability in type I cells at the same temperature was 6.0 +/- 0.9 x 10(-6) cm/s. These values resemble those of other barrier epithelial apical membranes, either isolated or in intact epithelia, and the water permeability values are far below those of other epithelial cells in culture. Transfection of MDCK type I cells with the major human urinary epithelial mucin, MUC1, led to abundant expression of the fully glycosylated form of the protein on immunoblots, and flow cytometry revealed that virtually all the cells expressed the protein. However, MUC1 had no effect on water or urea permeabilities. In conclusion, MDCK cells grown on semipermeable supports form a model barrier epithelium. Abundant expression of mucins does not alter the permeability properties of these cells.

    View details for Web of Science ID A1997XK45000008

    View details for PubMedID 9249593

  • Continent small-intestine reservoir construction: A tapered intussusceptum promotes sustained continence WORLD JOURNAL OF UROLOGY Donovan, J. F., HADE, D. K., Lavelle, J. P., Kwon, E. D. 1996; 14 (6): 370-374

    Abstract

    Developed for the study of dialysis in the continent jejunal reservoir (CJR), a novel, uncomplicated approach to achieve continence in construction of a small-bowel reservoir is presented. We utilize a technique of constructing a continent nipple valve, which entails the reduction or tapering of the intussusceptum prior to invagination into the reservoir. We have thus far performed the procedure successfully in 21 dogs. All animals have achieved absolute continence. Complications have occurred in two animals, neither complication involving the nipple valve. Pressure-volume cytometry in nine animals demonstrates continence in the awake animal at pressures of up to 40 cm H2O (volumes being limited by animal discomfort due to reservoir distention). In postmortem studies, reservoir capacities of > 1000 ml and pressures of > 70 cm H2O have been attained without loss of continence or prolapse of the nipple valve. Continence is sustained even when the reservoir and nipple valve are subjected to high intraluminal pressures. Incorporating a tapered intussusceptum, the continent reservoir provides absolute continence without the use of cumbersome mesh fixation or lithotropic intraluminal staples.

    View details for Web of Science ID A1996VY58700005

    View details for PubMedID 8986038

  • Permeability properties of the intact mammalian bladder epithelium AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Negrete, H. O., Lavelle, J. P., Berg, J., Lewis, S. A., Zeidel, M. L. 1996; 271 (4): F886-F894

    Abstract

    Because the mammalian bladder must store urine of composition which differs markedly from that of plasma for prolonged periods, the bladder permeability barrier must maintain extremely low permeabilities to substances which normally cross membranes relatively rapidly, such as water, protons, and small nonelectrolytes like urea and ammonia. In the present studies, permeabilities of the apical membrane of dissected rabbit bladder epithelium to water, urea, ammonia, and protons were measured in Ussing chambers and averaged (in cm/s) for water, 5.15 +/- 0.43 x 10(-5); for urea, 4.51 +/- 0.67 x 10(-6); for ammonia, 5.14 +/- 0.62 x 10(-4); and for protons, 2.98 +/- 1.87 x 10(-3), respectively. These permeability values are exceptionally low and are expected to result in minimal to no leakage of these normally permeable substances across the epithelium. Water permeabilities in intact whole rabbit bladders were indistinguishable from those obtained in the dissected epithelial preparation. Moreover, addition of nystatin to the apical solution of dissected epithelia rapidly increased water permeability in conjunction with loss of epithelial resistance. These results confirm that the apical membrane of the bladder epithelial cells represents the bladder permeability barrier. In addition, they establish a model system that will permit examination of how membrane structure reduces permeability and how epithelial injury compromises barrier function.

    View details for Web of Science ID A1996VL76500014

    View details for PubMedID 8898019

  • ACUTE GASTRITIS ASSOCIATED WITH SPIRAL ORGANISMS FROM CATS DIGESTIVE DISEASES AND SCIENCES Lavelle, J. P., Landas, S., Mitros, F. A., Conklin, J. L. 1994; 39 (4): 744-750

    Abstract

    Numerous studies implicated Helicobacter pylori as one causative agent producing gastritis and dyspepsia. Recent reports focus on another bacterium, Gastrospirillum hominis, as a possible pathogen producing gastritis. We report a 30-year-old researcher who became acutely ill with epigastric pain indicative of esophagitis or peptic ulcer disease. Gastritis and a gastric ulcer were observed endoscopically. Histological examination of the gastric mucosa revealed an acute gastritis and large spiral-shaped organisms. The spiral forms were present in large quantities in the gastric mucosa of experimental animals (cats) handled by the patient in his research. Electron microscopy confirmed that the organisms from the cat and patient were morphologically identical. The patient was successfully treated with bismuth subsalicylate. His symptoms resolved and the organisms were cleared from his stomach. This study provides evidence that another bacterium, a Gastrospirillum, may cause gastritis in man and may be transmitted from animal to man.

    View details for Web of Science ID A1994NF52200011

    View details for PubMedID 8149839

  • PRIMARY LOCALIZED AMYLOIDOSIS OF THE URINARY-BLADDER - A CASE-REPORT IRISH JOURNAL OF MEDICAL SCIENCE Keane, E. M., Hickey, D. P., Lavelle, J. P., Leader, M., McLean, P. A. 1989; 158 (1): 22-23

    Abstract

    Primary localised amyloidosis of the urinary bladder is a rare condition, of unknown aetiology, which can be successfully treated surgically. It has an excellent prognosis and a very low recurrence rate.

    View details for Web of Science ID A1989T839100007

    View details for PubMedID 2737854

  • THE EFFECTS OF CARDIOPULMONARY BYPASS ON IMMUNE-MECHANISMS OF MAN IRISH JOURNAL OF MEDICAL SCIENCE Lavelle, J. P., Duignan, J. P., NELIGAN, M. C. 1984; 153 (12): 431-436

    View details for Web of Science ID A1984TY77500004

    View details for PubMedID 6519929

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