Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells.

Acetylcholine is the primary parasympathetic neurotransmitter in the airways and is known to cause bronchoconstriction and mucus secretion. Recent findings suggest that acetylcholine also regulates aspects of remodelling and inflammation through its action on muscarinic receptors. In the present study, we aimed to determine the effects of muscarinic receptor stimulation on cytokine production by human airway smooth muscle cells (primary and immortalised cell lines). The muscarinic receptor agonists carbachol and methacholine both induced modest effects on basal interleukin (IL)-8 and -6 secretion, whereas the secretion of RANTES, eotaxin, vascular endothelial growth factor-A and monocyte chemoattractant protein-1 was not affected. Secretion of IL-8 and -6 was only observed in immortalised airway smooth muscle cells that express muscarinic M3 receptors. In these cells, methacholine also significantly augmented IL-8 secretion in combination with cigarette smoke extract in a synergistic manner, whereas synergistic effects on IL-6 secretion were not significant. Muscarinic M3 receptors were the primary subtype involved in augmenting cigarette smoke extract-induced IL-8 secretion, as only tiotropium bromide and muscarinic M3 receptor subtype selective antagonists abrogated the effects of methacholine. Collectively, these results indicate that muscarinic M3 receptor stimulation augments cigarette smoke extract-induced cytokine production by airway smooth muscle. This interaction could be of importance in patients with chronic obstructive pulmonary disease.

Pathophysiology and treatment of enuresis in adults.

Monosymptomatic nocturnal enuresis (MNE) in children is partly the result of inadequate reduction in the rate of urine output at night. This nocturnal polyuria is due to the lack of a rise in the anti-diuretic hormone, arginine vasopressin (AVP), and can be reduced or eliminated by treatment with desmopressin at bedtime. Since there is a 1% incidence of MNE among adults, this study investigated the circadian pattern of solute and water balance in nine young adult enuretics before and during desmopressin therapy and compared the results with nine-age- and sex-matched, healthy controls. Before treatment, enuretics and controls had similar total fluid intake, urine output, urine osmolality, plasma osmolality, plasma total protein, mean arterial pressure and plasma AVP. The circadian pattern of fluid intake was also normal in enuretics. This abnormality could not be attributed to a deficiency of plasma AVP or an increase in solute excretion, since both variables were similar to controls. Rather, their nocturnal polyuria appeared to be due to a marked nocturnal reduction in renal sensitivity to the antidiuretic effect of vasopressin. In seven enuretics, restudied during treatment with desmopressin (10-30 micrograms o.d.), circadian urine output was normal and enuresis was absent. These results indicate that: (i) The circadian pattern of urine output in healthy adults is largely due to a nocturnal decrease in solute excretion rather than a rise in plasma AVP; (ii) The subset of adults with persistent MNE also have nocturnal polyuria as a result of insensitivity to the antidiuretic action of AVP; (iii) These defects can be corrected by treatment with desmopressin.

Upper urinary tract abnormalities in multiple sclerosis patients with urinary symptoms.

OBJECTIVE: To determine the prevalence of upper urinary tract complications in multiple sclerosis (MS) patients with urinary symptoms, and to determine if an association exists between degree of physical impairment and upper urinary tract complications. DESIGN AND SETTING: A cohort study of MS patients seeking treatment at a freestanding, university-affiliated rehabilitation hospital. PARTICIPANTS: A referred sample of 48 patients with MS, exacerbation-free for 6 months with symptoms of neurogenic bladder dysfunction. For each patient, demographic data, disease characteristics, and urologic history was obtained. Using the Kurtzke Expanded Disability Status Scale (EDSS), participants were divided into a control (EDSS < 7) and study (EDSS >/= 7) group. INTERVENTION: Ultrasound examination of the upper urinary tract. MAIN OUTCOME MEASURE: Significant MS-related abnormalities of the upper respiratory tract. RESULTS: Ten of 48 patients (21%) had significant MS-related upper urinary tract abnormalities, which were evenly distributed between control and study groups. In the more disabled study group, abnormalities were associated with the symptom of urinary hesitancy (p < .05) and form of bladder management (p < .05). CONCLUSIONS: Routine screening for upper urinary tract complications appears indicated in a select group of MS patients with urinary symptoms.

Some aspects of striated urethral sphincter structure and function.

During the last 2 decades various routes of investigation have enhanced our knowledge of the striated urethral sphincter. Anatomic and neurophysiological studies as well as clinical evaluation in the form of urodynamic studies have demonstrated the components of the sphincter and its function. This information has provided the urologist with greater understanding of problems related to striated sphincter function.

Use of electrocoagulation in the treatment of vesicovaginal fistulas.

The role of electrocoagulation for the treatment of vesicovaginal fistulas has not been clearly defined. To determine the use of this therapeutic modality, 15 cases of fistulas treated with electrocoagulation were retrospectively reviewed. Fulguration represented the primary treatment in 12 patients and the secondary treatment in 3 after an initial attempt at open surgical closure failed. In all instances fistula size was estimated to be 3.5 mm. or less. A Bugbee electrode, which was inserted into the fistula either cystoscopically or vaginally, was used to destroy the epithelial lining of the fistula tract. Following the procedure the bladder was decompressed with a large indwelling Foley catheter for at least 2 weeks. Fulguration was successful as the sole treatment modality in 9 of 12 patients (75%) and as an alternative intervention after failure of an open surgical repair in 2 of 3 (66%). Therefore, 11 of the 15 women (73%) had complete resolution of the fistulas with this technique. We conclude that fulguration is usually effective in managing patients with vesicovaginal fistulas a few millimeters in size or less. This technique should be used as an initial treatment for appropriately selected patients and in women with small residual fistulas after open surgical failure.

Use of stresscath for diagnosing stress incontinence.

The modified fluid bridge (flow) test (MFBT) is a simple procedure for detecting bladder neck incompetency using a fluid-filled catheter. The Stresscath (Hollister) female diagnostic catheter is an improved version of the MFBT. We evaluated the ability of the Stresscath to detect bladder neck incompetence in the first 66 female patients referred for urodynamics. The absence or presence of stress incontinence was based on the results from history and physical examinations. The results from the Stresscath correlated with the history showed that the Stresscath had a sensitivity of 0.73 and a specificity of 0.88 in determining stress incontinence due to bladder neck incompetency. The results from the Stresscath correlated with the physical examination (Marshall test) showed that the Stresscath had a sensitivity of 0.86 and a specificity of 0.87 in determining stress incontinence due to bladder neck incompetence. The Stresscath was at least as accurate as the urethral pressure profile in the diagnosis of stress incontinence, at less capital cost.

Effect of intrathecal baclofen on bladder and sphincter function.

A programmable baclofen pump was implanted in 7 patients for relief of severe spasticity. The patients experienced improvement in bladder and sphincter function. This system would seem to be of value in improving lower urinary tract function in patients with diseases that produce marked spasticity.

Intrathecal baclofen infusion. Effect on bladder management programs in patients with myelopathy.

Intrathecal administration of Baclofen, a GABA agonist, through an implantable drug delivery pump has been demonstrated to be effective in the treatment of limb spasticity in patients with myelopathy. Three patients, followed before and after pump placement, experienced satisfactory spasticity relief and improvement in areas of self-care and mobility. Improvement in the bladder management programs of each patient was noted. These changes coincided with improvement on urodynamic studies, defined as either an increase in bladder capacity or a decrease in sphincter dyssynergia. Changes in bladder function were associated with the initiation of intrathecal therapy and with changes in pump-delivered dosages. In selected patients, intrathecal baclofen infusion can have a beneficial effect on bladder management programs.

The effect of sacral nerve stimulation for bladder control during pregnancy: a case report.

Neural stimulation was used to reduce bladder hyperreflexia and incontinence in a woman with myelodysplasia. The stimulation was delivered via an electrode placed in a sacral foramen and attached to a stimulator placed subcutaneously. The patient activated the device to inhibit the bladder and deactivated it to allow voiding. The device proved to be helpful in reducing bladder hyperreflexia and its use during pregnancy did not seem to have any adverse effect.

Defined in situ enumeration of T6 and HLA-DR expressing epidermal Langerhans cells: morphologic and methodologic aspects.

An essential prerequisite for the in situ enumeration of epidermal Langerhans cells (LCs) is the unequivocal identification of the desired cell type. We have examined over 250 cryostat sections of normal human skin to analyze morphologic and methodologic problems underlying the quantification of epidermal LCs, defined by anti-T6 (OKT6) and anti-HLA-DR (OKIal) immunoperoxidase staining. Our findings show that OKT6 reactivity of dendritic processes in cross-sectioned epidermis yields microscopic images which are not easy to analyze objectively. The morphology that we find leads us to categorize dendritic cells into 3 arbitrary types of T6+ LC profiles. In addition we describe criteria for the assessment of OKT6 staining patterns relating to the dendritic state of epidermal LCs. Preliminary quantitative data on this issue are discussed in relation to: epidermal thickness; the thickness of skin tissue sections; and the discrepancy between the number of T6+ and HLA-DR+ LCs. We hope that the principles outlined in this report may serve to overcome potential methodologic problems with quantitation of T6+ epidermal LCs in skin sections.

Inhibition of the external urethral sphincter and sacral reflex by anal stretch in spinal cord injured patients.

Relaxation of both detrusor and external sphincter muscles by mechanical stretch instead of cutaneous stimulation of the anal sphincter has been recognized and applied clinically for bladder emptying and for aiding catheterization in patients with spastic urethral sphincter. In a three-year study anal stretch was included as part of urodynamic examination in patients who could potentially use this method for bladder management. Anal stretch was found to inhibit the bulbocavernosus reflex and to be a useful alternative technique for bladder emptying in patients having complete paraplegia with normal hand function and with detrusor-sphincter dyssynergia. It is recommended that anal stretch combined with Credé or Valsalva maneuvers be a part of the urodynamic study of such patients to determine whether or not these techniques can be utilized for bladder management.

Urosonography in spinal cord injury patients.

Urosonography, ultrasound of the urinary tract, is a noninvasive imaging method used to evaluate renal masses, renal parenchymal disease, hydronephrosis, bladder volume and calculi. The applicability of ultrasound was studied in 54 spinal cord injury patients by correlating uroradiological examinations with ultrasound. Emphasis was placed on ultrasonic imaging of ureterectasis and vesicoureteral reflux. Ultrasound confirmed all positive radiographic findings of renal and bladder abnormalities (renal calculi, chronic pyelonephritis, trabeculated bladder and bladder calculi), and yielded additional information in 27 per cent of the kidney and 13 per cent of the bladder studies. Ultrasound was used to confirm vesicoureteral reflux in 56 per cent of the patients and ureterectasis in 33 per cent. It is recommended that spinal cord injury patients undergo a baseline excretory urogram followed by periodical ultrasound examinations to detect hydronephrosis, renal parenchymal disease, and renal and bladder calculi, and to measure bladder volume and residual urine. Whenever real-time equipment and experienced ultrasonologists are available ultrasound can be used as an alternate to voiding cystourethrography to detect vesicoureteral reflux.

Long-term intermittent catheterization in the spinal cord injury patient.

Intermittent catheterization was used as a means of long-term bladder management in 85 patients with spinal cord injury. Of these patients followup data revealed that 28 (33 per cent) had reflux and/or hydronephrosis. Treatment in 15 patients consisted of increasing the frequency of catheterization to every 4 hours and avoiding high fluid intake during a relative short interval. Sphincterotomy was done in 3 patients, while 10 were placed on an indwelling catheter because of an inability to adapt to or refusal of other forms of treatment. The upper urinary tract changes noted seemed to be related to increased intravesical pressure, either from too long an interval between catheterizations or from marked detrusor hyperreflexia with sphincter obstruction. Close followup seems necessary in these patients.

Bladder electromyography: response to electric stimulation and to terbutaline.

Four patients with traumatic spinal cord injuries and paraplegia received electric stimulation of the conus medullaris. An additional 5 patients with traumatic spinal cord injuries and paraplegia received terbutaline for asthma. All 9 patients were studied with bladder and external urethral sphincter electromyography (EMG). Bladder pressures were recorded in the electric stimulation group and cystometry in the terbutaline group. The electric impulses were recorded without attenuation, and bladder and external urethral sphincter contractility increased. Terbutaline reduced the bladder's electric activity and pressure at capacity without affecting external urethral sphincter function. More evaluations of terbutaline's effect on the bladder are necessary to determine its applicability to incontinence problems.

Extensive suprapubic vesicocutaneous fistula following trauma.

There are few reports on extensive suprapubic vesicocutaneous fistulas. We report the problems encountered in the closure of these fistulas following lower abdominal trauma. Two patients are described in whom the trauma produced extensive loss of skin, fascia and muscle, leaving the bladder exposed and open. Despite several attempts at bladder closure the bladder repair always failed and the fistula remained open. It was necessary to cover the subsequent bladder closure with overlying muscle, fascia and skin to obtain a successful closure. The techniques of closure are explained.

Reusable catheter for long-term sterile intermittent catheterization.

A new resterilizable, low cost, and convenient catheter for long-term sterile intermittent catheterization of the neurogenic bladder is described. Average self-catheterization time is 2 minutes. It can be performed successfully in a wheelchair. Estimated average cost per catheterization is 10 to 20 cents. The reduced cost and greater convenience of the Wu Reusable Catheter make sterile long-term intermittent catheterization feasible for spinal cord injured patients. This should lead to reduction of urologic morbidity encountered with indwelling and external catheterization.

Urethral sphincter activity following acute spinal cord injury.

We studied 44 patients with spinal cord injury during the first 72 hours after injury to determine the functional status of the bladder and external urethral sphincter. The studies included determination of the bulbocavernosus reflex, cystometry and sphincter electromyogram. In patients with lesions above the sacral cord the bulbocavernosus reflex was present. In nearly all of these patients the external sphincter activity increased with bladder filling. In all but 1 patient with injury to the sacral cord the bulbocavernosus reflex could not be elicited and the sphincter electromyogram did not increase with bladder filling.

Augmentation of bladder contractility after beta-adrenergic blockade in spinal cord injured patients.

Six spinal cord injured patients were evaluated with cystometry, bladder electromyography, and external urethal spincter pressure profiles before and after propranolol hydrochloride administration. Bladder contractility was significantly augmented, and therefore was associated with decreased beta-sympathetic bladder stimulation. The results of these clinical neurophysiological investigations suggest inhibitory influences upon the smooth muscle of the human urinary bladder via beta-sympathetic receptors.