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H Henry Lai

Publications and source records attributed to H Henry Lai.

4 recordsLinked to original sources

The impact of detrusor overactivity on the management of stress urinary incontinence in women.

The presence of overactive bladder symptoms, urodynamic detrusor overactivity, and urge incontinence can complicate the diagnosis and management of stress urinary incontinence in women. The exact pathophysiology of mixed incontinence is not well characterized; in some patients, the stress and urge etiology may be pathologically linked. The role of urodynamics in evaluating patients with mixed incontinence remains controversial. Conservative therapies, such as bladder training, pelvic floor exercise, biofeedback, and electrical stimulation, offer moderate success in women with mixed incontinence. Surgery (colposuspension, bladder neck pubovaginal slings, and midurethral slings) offers excellent subjective and objective cure rates in patients with mixed incontinence. Preoperative detrusor overactivity is cured consistently 50%of the time with colposuspension and slings. Overall, the presence of preoperative detrusor overactivity does not appear to significantly worsen the outcome of conservative and surgical treatments for stress urinary incontinence in women.

Female↗

Loss of caveolin-1 expression is associated with disruption of muscarinic cholinergic activities in the urinary bladder.

Caveolin-1 (Cav1), a structural protein of caveolae, plays cell- and context-dependent roles in signal transduction pathway regulation. We have generated a knockout mouse homozygous for a null mutation of the Cav1 gene. Cav1 knockout mice exhibited impaired urinary bladder contractions in vivo during cystometry. Contractions of male bladder strips were evoked with electric and pharmacologic stimulation (5-40 Hz, 1-10 microM carbachol, 10 mM alpha,beta-methylene ATP, 100 mM KCl). Acetylcholine (ACh) and norepinephrine (NE) release from bladder strips were measured with a radiochemical method by incubating the strips with 14C-choline and 3H-NE prior to electric stimulation, whereas ATP release was measured using the luciferin-luciferase assay with a luminometer. A 60-75% decline in contractility was observed when Cav1 knockout muscle strips were stimulated with electric current or carbachol, compared to wildtype muscle strips. No difference in contractility was noted when contractions were evoked either by the purinergic agonist alpha,beta-methylene ATP, or by extracellular potassium. To investigate the relative contribution of non-cholinergic activity to bladder contractility, the amplitude of the electric stimulation-evoked contractions was compared in the presence of the muscarinic antagonist atropine (1 microM). While the non-muscarinic (purinergic) response was unaltered, muscarinic cholinergic response was principally disrupted in Cav1 knockout mice. The loss of Cav1 gene expression was also associated with a 70% reduction in ACh release. NE and ATP release was not altered. It is concluded that the loss of caveolin-1 is associated with disruption of M3 muscarinic cholinergic activity in the bladder. Both pre-junctional (acetylcholine neurotransmitter release from neuromuscular junctions) and post-junctional (M3 receptor-mediated signal transduction in bladder smooth muscles) mechanisms are disrupted, resulting in impaired bladder contraction.

Acetylcholine↗

Pharmacologic treatment for detrusor overactivity.

Recent pharmacologic treatment for detrusor overactivity has resulted in more favorable side effect profiles, not only because of the use of different drug delivery systems for older drugs but perhaps also due to the improved bladder selectivity of newer antimuscarinic agents. These developments translate into higher patient compliance and better long-term results with the newer agents over generic immediate-release oxybutynin for the treatment of the overactive bladder.

Benzhydryl Compounds↗

Selecting a medical therapy for overactive bladder.

Immediate-release oxybutynin was the gold standard for pharmacologic treatment of overactive bladder for nearly 30 years. Intolerable systemic side effects, in particular dry mouth, limited its clinical utility, resulting in poor patient compliance with dosing regimens. Multiple studies have demonstrated the vastly superior tolerability of tolterodine, extended-release tolterodine, and extended-release oxybutynin over that of immediate-release oxybutynin at equivalent doses, and in the case of extended-release oxybutynin even to twice the dose of the original immediate-release form. With different drug delivery systems and, perhaps, with better bladder selectivity, these new oral agents have favorable side effect profiles, which translate into higher patient compliance and fewer treatment withdrawals or dosage reductions.

Journal Article↗