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This review focuses on what we consider to be the most important findings of the last year relating to the smooth muscle of the lower urogenital system and the different levels of regulation that control its contraction and relaxation. One level is through modulation of the smooth muscle itself or its environment. Recent findings examining myosin isoform composition and collagen content as well as mechanisms that appear to be involved in inducing hyperplasia/hypertrophy of smooth muscle are described. Another method of regulation is via calcium-dependent phosphorylation of the regulatory light chain of myosin, which increases its activity. Interesting results indicating an uncoupling of force from calcium in the bladder are discussed. A third level of regulation is pharmacologic. Thus, the most recent findings related to receptor subtypes, including muscarinic, endothelin, alpha-adrenergic and nicotinic receptors, are presented. In addition, the effects of diabetes, incontinence, and partial bladder outlet obstruction on these modes of contractile regulation are also discussed.
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PMID:Lower urinary tract physiology and pharmacology. 1208 18

Sildenafil utilization was prospectively evaluated among 153 men with a history of erectile dysfunction (ED)-prescription drug use prior to starting sildenafil and 164 men who were new starters of ED-prescription drugs. Further, some determinants of sildenafil discontinuation were identified. During a median follow-up period of 18 months 45% of all patients discontinued sildenafil treatment, regardless of earlier treatment history. However, patients with a history of drug treatment for ED were nearly eight times as likely to switch or re-start another ED-prescription drug after discontinuing sildenafil compared to previously untreated users. Age >60 y, diabetes medication, nitrate use, and use of incontinence pads (a proxy for disease/surgery in the pelvic region) were associated with an increased likelihood of discontinuing sildenafil. Although the introduction of sildenafil reduced the barrier to seek medical help for erectile problems, sildenafil treatment failure in previously untreated patients results in a high dropout rate from further ED drug treatment of any kind.
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PMID:Incidence and determinants of sildenafil (dis)continuation: the Dutch cohort of sildenafil users. 1215 15

The increasing incidence of asymptomatic bacteriuria and symptomatic urinary tract infections in the elderly requires a detailed consideration of this problem including age-specific medical and social risk factors. The increasing need for care, age- and gender-related complicating factors such as subvesical obstruction, adnexal infections, and incontinence, and the need for catheterization are predominant. Specific age-related diseases such as diabetes mellitus, pharmacodynamic alterations of antimicrobial substances, and changes in the vaginal colonization make increased demands on therapeutic strategies. Urologic implications resulting from this set of difficulties have not yet been investigated sufficiently and need further evidence-based work-up.
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PMID:[Urogenital infections in the elderly]. 1221 48

The comorbidities of diabetes mellitus were evaluated in an Asian American population with podiatric symptoms living in southern California. The three most common nonpedal complaints in men were blurred vision (73.6%), hypertension (64.1%), and erectile dysfunction (52.3%) and in women were blurred vision (84.5%), incontinence (71.5%), and low-back pain with radiculopathy-like symptoms (56.5%). The most significant finding was that only 3.2% of all patients had any previous knowledge or understanding of the risks of foot infection, ulceration, and amputation secondary to diabetes mellitus. The prevalence of diabetes mellitus in ethnic populations once considered practically exempt continues to rise steadily, and Asians living in the United States are becoming casualties of diabetes mellitus and its complications.
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PMID:Comorbidities associated with diabetic foot complications among Asian Americans in southern California. 1253 55

Kidney transplantations are being performed in every increasing numbers, and, in addition to specialist centres, nephrologists, general practitioners and urologists are more frequently being involved in the provision of aftercare. The major urological complications seen after transplantation include ureteral stenosis and necrosis, incontinence and impotence, lymphoceles, arterial stenosis, infections of the urinary tract and adnexa, as well as--the most serious complication--malignant tumours. In addition, the immunosuppression required by these patients is often associated with secondary disorders such as hypertension, steroid-related diabetes, hyperlipidemia and infections. Against the background of progressive organic deficiency it is of particular importance to identify such complications and to treat them adequately, or to prevent them from occurring, thus ensuring the longest possible survival of transplant and patient and improved quality of life.
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PMID:[Follow-up in kidney transplantation. Which complications are likely?]. 1263 37

Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Despite its relationship to an increased risk of cardiovascular mortality and its association with multiple symptoms and impairments, the significance of DAN has not been fully appreciated. The reported prevalence of DAN varies widely depending on the cohort studied and the methods of assessment. In randomly selected cohorts of asymptomatic individuals with diabetes, approximately 20% had abnormal cardiovascular autonomic function. DAN frequently coexists with other peripheral neuropathies and other diabetic complications, but DAN may be isolated, frequently preceding the detection of other complications. Major clinical manifestations of DAN include resting tachycardia, exercise intolerance, orthostatic hypotension, constipation, gastroparesis, erectile dysfunction, sudomotor dysfunction, impaired neurovascular function, "brittle diabetes," and hypoglycemic autonomic failure. DAN may affect many organ systems throughout the body (e.g., gastrointestinal [GI], genitourinary, and cardiovascular). GI disturbances (e.g., esophageal enteropathy, gastroparesis, constipation, diarrhea, and fecal incontinence) are common, and any section of the GI tract may be affected. Gastroparesis should be suspected in individuals with erratic glucose control. Upper-GI symptoms should lead to consideration of all possible causes, including autonomic dysfunction. Whereas a radiographic gastric emptying study can definitively establish the diagnosis of gastroparesis, a reasonable approach is to exclude autonomic dysfunction and other known causes of these upper-GI symptoms. Constipation is the most common lower-GI symptom but can alternate with episodes of diarrhea. Diagnostic approaches should rule out autonomic dysfunction and the well-known causes such as neoplasia. Occasionally, anorectal manometry and other specialized tests typically performed by the gastroenterologist may be helpful. DAN is also associated with genitourinary tract disturbances including bladder and/or sexual dysfunction. Evaluation of bladder dysfunction should be performed for individuals with diabetes who have recurrent urinary tract infections, pyelonephritis, incontinence, or a palpable bladder. Specialized assessment of bladder dysfunction will typically be performed by a urologist. In men, DAN may cause loss of penile erection and/or retrograde ejaculation. A complete workup for erectile dysfunction in men should include history (medical and sexual); psychological evaluation; hormone levels; measurement of nocturnal penile tumescence; tests to assess penile, pelvic, and spinal nerve function; cardiovascular autonomic function tests; and measurement of penile and brachial blood pressure. Neurovascular dysfunction resulting from DAN contributes to a wide spectrum of clinical disorders including erectile dysfunction, loss of skin integrity, and abnormal vascular reflexes. Disruption of microvascular skin blood flow and sudomotor function may be among the earliest manifestations of DAN and lead to dry skin, loss of sweating, and the development of fissures and cracks that allow microorganisms to enter. These changes ultimately contribute to the development of ulcers, gangrene, and limb loss. Various aspects of neurovascular function can be evaluated with specialized tests, but generally these have not been well standardized and have limited clinical utility. Cardiovascular autonomic neuropathy (CAN) is the most studied and clinically important form of DAN. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function as measured by heart rate variability (HRV) is strongly (i.e., relative risk is doubled) associated with an increased risk of silent myocardial ischemia and mortality. The determination of the presence of CAN is usually based on a battery of autonomic function tests rather than just on one test. Proceedings from a consensus conference in 1992 recommended that three tests (R-R variation, Valsalva maneuver, and postural blood pressure testing)or longitudinal testing of the cardiovascular autonomic system. Other forms of autonomic neuropathy can be evaluated with specialized tests, but these are less standardized and less available than commonly used tests of cardiovascular autonomic function, which quantify loss of HRV. Interpretability of serial HRV testing requires accurate, precise, and reproducible procedures that use established physiological maneuvers. The battery of three recommended tests for assessing CAN is readily performed in the average clinic, hospital, or diagnostic center with the use of available technology. Measurement of HRV at the time of diagnosis of type 2 diabetes and within 5 years after diagnosis of type 1 diabetes (unless an individual has symptoms suggestive of autonomic dysfunction earlier) serves to establish a baseline, with which 1-year interval tests can be compared. Regular HRV testing provides early detection and thereby promotes timely diagnostic and therapeutic interventions. HRV testing may also facilitate differential diagnosis and the attribution of symptoms (e.g., erectile dysfunction, dyspepsia, and dizziness) to autonomic dysfunction. Finally, knowledge of early autonomic dysfunction can encourage patient and physician to improve metabolic control and to use therapies such as ACE inhibitors and beta-blockers, proven to be effective for patients with CAN.
Diabetes Care 2003 May
PMID:Diabetic autonomic neuropathy. 1271 21

Bladder overactivity (OAB) is a common disease with a socioeconomic impact comparable to diabetes mellitus. As life expectancy rises in industrialized countries the importance of OAB will further increase. The International Continence Society (ICS) recently reported a modified terminology for lower urinary tract function and established the symptom-based term OAB. The etiology of OAB comprises neurogenic and non-neurogenic detrusor hyperactivity as well as detrusor hypersensitivity. Neurogenic detrusor hyperactivity may be caused by insufficient cortical inhibition, degenerative neuropathies, and spinal cord lesions, whereas bladder aging, bladder outlet obstruction, and chronic bladder irritation (UTI, stones, tumors) are possible causes for non-neurogenic detrusor hyperactivity. Since most epidemiologic surveys focus on urge incontinence without considering urgency frequency without incontinence, epidemiologic data concerning OAB are rare. Two recently published multinational prevalence studies from Europe and Asia show different prevalence values [Europe: 15.6% (men), 17.4% (women); Asia: 53.1%(women)], which may be due to methodological differences. Both studies report an increase of OAB prevalence corresponding with age. The cumulative incidence of OAB is rising faster in aging males than in aging females. Two-thirds of the European and one-fourth of the Asian individuals affected by OAB complained about impaired quality of life, but only 60% of the European and 21% of the Asian sufferers have talked to a doctor or sought treatment. One out of four patients visiting their health care professional for OAB symptoms is currently under medication. To avoid high treatment costs and side effects, pharmacotherapy (e.g., antimuscarinics) should only be given after detailed diagnostic evaluation.
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PMID:[Epidemiology and etiology of overactive bladder]. 1285 68

We investigated the difficulties involved in assessing post prostatectomy voiding according to 20 nurses working in urology and dermatology wards. Problems they encountered included completing a urination (frequency/volume) chart and performing an assessment. We constructed a hourly urination chart for basic nursing education in urinary incontinence. This was used for a 76-year-old male patient with hypertension and diabetes mellitus who underwent a prostatectomy. Urination was recorded for 17 consecutive days after catheter removal. Detailed pathological findings were more distinct in the hourly rather than daily recordings of voluntary micturition. Voluntary micturition appeared 12 h after catheter removal, but it was very scanty. After the onset of urination, frequency and amount of daily voluntary micturition was inversely related to incontinence during the 17 days after catheter removal. We drafted a set of urination recovery stages to enable the analysis of a patient's urination status. Nurses understood its importance and were able to reach a consensus on how to manage patients with postoperative incontinence. We have constructed a practical system for use by specialist urology nurses.
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PMID:Urination assessment after the removal of bladder catheter using a novel urination chart. 1287 20

Drugs acting on beta(1)- and beta(2)-adrenergic receptors are widely used for the clinical management of a large number of cardiovascular and respiratory pathologies. In the last decade, the discovery of the third subtype of beta receptors, the beta(3)-adrenoceptor, gave a further pharmacological target for the development of new selective drugs. Initially, a potential therapeutic use of beta(3)-selective agents seemed to be restricted to agonists, for the treatment of metabolic diseases, such as obesity, non-insulin-dependent diabetes, urinary frequency and incontinence. More recently, some interesting theories about a negative role played by the cardio-depressant activity of myocardial beta(3)-adrenoceptors in heart failure, seemed to justify a clinical use of beta(3)-antagonists in the last phases of this cardiac disease. Following the indications deriving from previous experimental work, the beta-antagonist properties of newly-synthesised (R,S)-(E)-oximeethers of 2,3-dihydro-1,8-naphthyridine and of 2,3-dihydrothiopyrano[2,3-b]pyridine were evaluated, in order to identify some useful structure-activity relationships, which might account for selectivity towards the three beta-subtypes and, in particular, the beta(3)-adrenoceptor. Among the various observations regarding possible structure-activity relationships, able to explain the pharmacodynamic patterns of the synthesised compounds on the three subtypes of beta-adrenoceptors, the most significant data derived from the evaluation of the beta(3)-blocking properties of some oximeethers of 1,8-naphthyridine derivatives. In these molecules, although the presence of the large substituents in position 7, such as 4-chloro-phenoxy- or 4-t-butyl-phenoxy groups determined a dramatic decline in both the beta(1)- and beta(2)-activities, this structural characteristic had a modest influence on the beta(3)-affinity, which was only slightly lower. Hence, this last structural requirement of oximeethers of 1,8-naphthyridine derivatives seems to represent a useful expedient to induce an appreciable selectivity towards the beta(3)-receptor, through a markedly negative effect on the beta(1)- and beta(2)-activities rather than an increase in the beta(3)-affinity.
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PMID:Synthesis and beta-blocking activity of (R,S)-(E)-oximeethers of 2,3-dihydro-1,8-naphthyridine and 2,3-dihydrothiopyrano[2,3-b]pyridine: identification of beta 3-antagonists. 1460 53

Bladder dysfunction can result from pathological changes in the bladder itself, of its central neurological regulation, (BPS), or of non-urological diseases such as diabetes or heart failure. Medication-induced bladder dysfunction can mostly be treated by simple changes in the pharmacological therapy. Bladder dysfunction can be induced pharmacologically by activating or inhibitory influences on adrenergic, sympathetic, beta-receptor-induced relaxation of the detrusor, alpha-receptor-induced contraction of the bladder neck, or cholinergic, parasympathetic, muscarinic receptor-induced contraction of the detrusor. Diuretics can increase urine production, thus possibly leading to incontinence. If incontinence occurs in patients, treatment should be stopped if possible and additional pharmacological therapy should not be started before medication-induced bladder dysfunction is excluded.
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PMID:[The medication-induced dysfunction of the urinary bladder]. 1466 86


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