Smokeless nicotinergic stimulation of vasopressin secretion in patients with persisting nocturnal enuresis and controls.

OBJECTIVE: This study aimed to evaluate the effect of nicotine stimulation on pituitary release of plasma arginine vasopressin (P(AVP)) in patients with primary monosymptomatic nocturnal enuresis (PMNE) and healthy control subjects. MATERIAL AND METHODS: Postpubertal teenagers and adult enuretics as well as control subjects were enrolled into the study and admitted to hospital for measurements of P(AVP) in relation to intake of orally administered nicotine. Sixteen patients with PMNE (9 females, 7 males; aged 15-51 years, mean 23.5) and nine normal subjects (4 females, 5 males; aged 24-31 years, mean 27.3) were studied. The enuretics were characterized prior to investigation as either 1-desamino-8-D-arginine vasopressin (DDAVP) responders (n = 8; 16-51 years, mean 28.9) or DDAVP non-responders (n = 8; 15-24 years, mean 18.1) based on the reduction in the number of wet nights. P(AVP), mean arterial blood pressure (MAP) and heart rate (HR) were measured 0, 5, 10, 15 and 30 min, and plasma osmolality (P(osm)) 0 and 30 min after receiving 4 mg nicotine (Nicorette, Pharmacia & Upjohn) chewing gum. RESULTS: In the compiled material a slight but statistically significant increase was observed in P(AVP) at 30 min compared with baseline levels, concurrent with significant rises in MAP and HR above baseline levels at 15 and 30 min. No difference was seen in P(osm) before and after nicotine administration. No other significant variation over time, assessed by an ANOVA, was detected. No difference was encountered in any measured parameter between controls and enuretics or between DDAVP responders and non-responders. CONCLUSION: Smokeless nicotine chewing gum induces non-osmotic vasopressin release in humans. The secretory AVP capacity to this stimulation is normal in PMNE.

Clinical options for imipramine in the management of urinary incontinence.

Urinary incontinence is a common disorder in both childhood and adulthood. Proper treatment depends on insight into the pathophysiology and pharmacology of the lower urinary tract. This article reviews the mechanism of action of an old but commonly used drug, the tricyclic antidepressant agent imipramine, in nocturnal enuresis and stress and urge incontinence with reference to neuropharmacology and the relevant pathophysiology.

Increased delta component in computerized sleep electroencephalographic analysis suggests abnormally deep sleep in primary monosymptomatic nocturnal enuresis.

OBJECTIVE: The aim of this study was to investigate sleep and the sleep modulating effect of 1-desamino-8-D-arginine vasopressin (DDAVP) in patients with primary monosymptomatic nocturnal enuresis and controls by means of both conventional polysomnography and computerized electroencephalographic (EEG) power analysis. MATERIAL AND METHODS: Adolescents or adults with primary monosymptomatic nocturnal enuresis (n = 11, 8 females, 3 males: mean age 23.0 +/- 9.8, range 15-49 years) and normal subjects (n = 10, 7 females, 3 males: mean age 23.2 +/- 5.4, range 14-32 years) were admitted to the sleep laboratory of the University Hospital of Aarhus, Denmark, for the investigation of sleep over four consecutive nights. A fixed day-to-night cycle was maintained. Night-time was defined as 23.00-07.00 h. The 1st and 3rd nights were completed without intervention. Sleep was modulated on the 2nd night by a waterload to induce nocturnal micturition. On the 4th night all subjects received DDAVP spray applied intranasally at bedtime. Sleep was evaluated by manual polysomnography according to the rules of Rechtschaffen and Kales and by computerized EEG power analysis on the 1st, 3rd and 4th nights. EEG power was calculated as total power and as power assigned to specific EEG frequency bands. RESULTS: Enuretics showed a significant increase in the EEG delta power component during baseline sleep compared with controls, whereas no difference was encountered using a manual sleep score. During recovery sleep on the 3rd night EEG power in the enuretic group was increased in all EEG frequency bands apart from the alpha and sigma bands and associated with a shortened total sleep period. DDAVP was not found to influence sleep to any significant extent. CONCLUSIONS: EEG power analysis indicates an increased depth of sleep in enuretics inadequately reflected by a conventional polysomnographic technique. No sleep-modulating effect of DDAVP was detected.

The efficacy of DDAVP is related to the circadian rhythm of urine output in patients with persisting nocturnal enuresis.

OBJECTIVE: Desmopressin may be a useful treatment in some, but not all, patients with nocturnal enuresis. We have evaluated a relation between nocturnal urine output in patients with primary monosymptomatic nocturnal enuresis and the treatment response to synthetic vasopressin. DESIGN: Adolescent or adult enuretics and normal subjects were enrolled in the study and admitted to hospital for a 24 hour investigation of the diurnal variation in urine output, plasma vasopressin (AVP) and plasma atrial natriuretic peptide (ANP). The enuretics were characterized prior to investigation as either 1-desamino-8-D-arginine vasopressin (DDAVP) responders or non-responders. During admission the fluid intake was restricted to 25 ml/kg per day. PATIENTS: Twenty-four patients (15-37 years) with primary monosymptomatic nocturnal enuresis and 9 normal subjects (24-31 years). MEASUREMENTS: Circulating levels of AVP, ANP, plasma electrolytes and plasma osmolality were measured (1400, 2000, 2300, 0200, 0500 and 0800 hours) together with urine volume, urine osmolality and urine electrolytes during daytime and nighttime. Tubular reabsorptive capacity for water, osmoles and creatinine were assessed as well as urinary and fractional excretion rates of sodium and potassium. RESULTS: Controls and DDAVP non-responders had a significant decrease in urine output at night concomitant with a significant plasma AVP amplitude in peak/nadir values although both groups lacked a significant nocturnal increase in AVP. In contrast, in DDAVP responders there was no circadian variation in urine output and thus a nocturnal polyuria together with no oscillation in plasma AVP. The DDAVP responding group had a nocturnal urine production significantly larger than the two other groups. However, the mean 24 hour AVP levels were similar in all groups. The excessive urine production at night in DDAVP responders was accompanied by nocturnal natriuresis due to an increased fractional excretion of sodium. In contrast, nocturnal antidiuresis in controls and DDAVP non-responding enuretics coincided with diminished sodium excretion. Average ANP levels were elevated in both enuretic groups compared to normals, whereas a circadian variation was detected only in the latter. CONCLUSION: It is concluded that DDAVP responsiveness is linked to the nocturnal urine production and that no pathophysiological role can be ascribed to AVP or ANP in DDAVP refractory adolescent and adult enuretics. Moreover, it is suggested that an abnormal tubular handling of sodium may contribute to the nocturnal polyuria seen in DDAVP responders.

Single dose imipramine reduces nocturnal urine output in patients with nocturnal enuresis and nocturnal polyuria.

PURPOSE: We investigated the effect of imipramine on nocturnal urine output in patients with nocturnal enuresis. MATERIALS AND METHODS: There were 15 monosymptomatic enuretic patients 15 to 37 years and 8 control subjects 25 to 32 years old. We measured nocturnal urine output, urine osmolality, creatinine clearance, osmolal clearance, free water clearance, excretion of solutes, fractional excretion of sodium, fractional excretion of potassium and plasma vasopressin with and without a single oral dose of imipramine (1 mg./kg. of body weight) taken at 8 p.m. RESULTS: Baseline studies showed significantly larger and less concentrated nocturnal urine among enuretics compared with controls. We observed a marked antidiuretic effect of imipramine in 6 enuretics with severe nocturnal polyuria. The imipramine induced decrease in urine output was accompanied by reduced osmolal clearance. Approximately a third of the observed decrease in solute excretion was attributed to lower excretion of sodium and potassium. The remaining two-thirds were most likely caused by an increased tubular reabsorption of urea, which may be secondary to a sympathomimetic effect of imipramine tubules, possibly because of altered adrenal medullary function with an increase in proximal tubular sodium and water reabsorption. The resultant lower tubular flow rate facilitates tubular reabsorption of urea in the distal part of the nephron. CONCLUSIONS: Imipramine has a vasopressin independent antidiuretic effect if nocturnal polyuria is present. The antidiuretic effect of imipramine can be attributed primarily to increased alpha-adrenergic stimulation in the proximal tubules with a secondary increased urea and water reabsorption more distally in the nephron.

Long-term home studies of water balance in patients with nocturnal enuresis.

A 2-week, home-based study was conducted on 75 children with nocturnal enuresis to monitor the frequency of enuretic episodes and the volume of nocturnal urine production. The objectives of the study were to correlate nocturnal urine production to the occurrence of nocturnal enuresis and response to desmopressin (Minirin, DDAVP) treatment. Furthermore, patient compliance was evaluated. Enuresis episodes and nocturnal urine production was recorded every night during two base-line weeks without treatment and during 2 weeks with 20-40 micrograms desmopressin at bedtime. During both periods fluid intake and micturition volumes were recorded for 2 days. Desmopressin response was defined as > 50% reduction in wet nights during treatment. It was found that patient compliance was acceptable in most patients. Regarding urine output it was found that base-line nocturnal urine production was significantly higher during nights when enuresis occurred than during "dry" nights and significantly higher in desmopressin responders compared with desmopressin non-responders. During treatment with desmopressin, nocturnal urine production in desmopressin responders decreased to levels similar to those of non-responders. The results confirm inpatient circadian studies of urine output and emphasise the importance of nocturnal polyuria in patients with monosymptomatic enuresis. The response to desmopressin was found to correlate with the occurrence of nocturnal polyuria. Home studies were considered to be a useful tool in the characterisation of patients with nocturnal enuresis.

The effect of the full bladder on vasopressin secretion in healthy young adults.

Interactions between the central nervous system, bladder and kidneys have been investigated for many years in animal studies and have shown that bladder distension, in animals, leads to decreased urine production. The objectives of the current study were to determine the effect of a full bladder on urinary output, vasopressin secretion and urine osmolality in humans. The study involved healthy volunteers. They were studied for a period of 48 hours. This period included two 24-hour studies, one involving regular and frequent voidings (to produce a minimal bladder filling) and the other voiding postponement (to produce maximal bladder distension). In contrast to enuresis studies a circadian rhythm of vasopressin secretion was observed in the males involved in this study, whereas no significant rhythm of vasopressin secretion could be detected in the female subjects. However, this study was unable to confirm that, in humans, a full bladder causes a decrease in urine production, an increase in vasopressin secretion or an increase in urine osmolality.

The pituitary gland in nocturnal enuresis: MR findings.

Nocturnal enuresis is considered a benign condition partially explained by a defect circadian rhythm of vasopressin. An organic cause may be responsible for an abnormal pituitary function, when enuresis persists into adulthood. In the present study the pituitary gland and surroundings of 8 adults suffering from primary monosymptomatic nocturnal enuresis were studied by magnetic resonance imaging. The pituitary gland appeared normal in all, except from a Rathke's cleft cyst observed in one patient. This cleft cyst was not considered to be clinically important. It was concluded, that severe nocturnal enuresis persisting into adulthood is not likely to be combined with detectable pathology on magnetic resonance imaging of the pituitary gland.

[Alternative treatment forms used by patients with muscular atrophy. A questionnaire study of the use of alternative treatment by 345 patients with muscular atrophy]. / Muskelsvindramtes brug af alternativ behandling. En enqueteundersøgelse af 345 muskelsvindramtes brug af alternative behandlinger.

An investigation about the use of alternative treatment by a group of persons with muscular atrophy revealed that 24% had employed alternative treatment during the period 1.1.1983-1.4.1986. This is probably a greater proportion than in the Danish population as a whole. Patients with muscular atrophy were subdivided into three groups on the basis of their ability to function in daily life. No significant connection was found between the degree of loss of function and alternative treatment as regards the frequencies of alternative treatment and the numbers of treatments employed. A given form form of treatment was most frequently recommended by an unaffected acquaintance. Physical forms of treatment such as zone therapy and chiropractics were employed more frequently than chemical forms of therapy. Less than half of the patients were satisfied with the results of treatment. Treatment was often concluded in a negative manner. Patients considered that, in contrast to the alternative therapist, the doctor performs the best and most thorough examination and provides them with the best information about their condition.