Awakening salivary cortisol levels of children with sleep bruxism.

UNLABELLED: The study of factors potentially associated with sleep bruxism (SB) may contribute to a better understanding of its nature and etiology. OBJECTIVES: In this way, this cross-sectional study aimed to evaluate the association between SB and salivary cortisol levels, heart rate, and other parafunctional habits. DESIGN AND METHODS: Data were collected in 100 healthy caries-free children of both genders, aged 7.23 ± 0.60 years, with (n=27) and without (n=73) signs and symptoms of SB by interview with the parents and clinical and physical examination. Salivary cortisol was measured immediately after waking up and 30min after awakening for the determination of the area under the response curve (AURC). Data were analyzed by descriptive statistics, normality test, and Spearman correlation test; a stepwise logistic regression model was used to verify the association between SB, as the dependent variable, and age, gender, body mass index (BMI), heart rate, presence of sucking habit, nail biting, enuresis, and AURC (α=0.05). RESULTS: AURC did not correlate with BMI and heart rate. Only AURC showed a significant negative association with SB, while age, gender, BMI, heart rate and other parafunctional habits did not associate with SB. CONCLUSION: In the studied sample, children with SB were more likely to present low concentrations of awakening salivary cortisol.

Melatonin rhythm in children with enuresis.

OBJECTIVE: To study the circadian rhythm of melatonin in children with enuresis. PATIENTS AND METHODS: Twenty-five children, divided into two groups (enuretic patients and controls) were assessed; salivary samples were collected to measure melatonin by radioimmunoassay using commercial kits. Friedman two-way anova and Wilcoxon tests were used to assess the circadian rhythm of melatonin, and anova with between-patient factors and Mann-Whitney tests to compare melatonin values and groups. RESULTS: Both groups had statistically significant differences in melatonin concentration during the 24-h period (both P < 0.001), with a circadian rhythm; the highest values were always at approximately 04.00 hours. There were no significant differences overall in melatonin values between cases and controls, but patients had lower peak values than controls at 04.00 hours, and higher melatonin levels at 24.00 hours, but with no significant differences. CONCLUSION: There was some evidence for minor disturbances in the circadian rhythm of melatonin as a cause of enuresis, but the rhythm was not grossly disrupted.

Abnormal circadian rhythm of diuresis or nocturnal polyuria in a subgroup of children with enuresis and hypercalciuria is related to increased sodium retention during daytime.

PURPOSE: In a subgroup of children with enuresis an increase in nighttime water and solute excretion has been documented. To investigate if modifications in renal function are involved in nocturnal enuresis, we assessed circadian variation in natriuresis and tubular sodium handling in polyuric hypercalciuric children. MATERIALS AND METHODS: A total of 10 children with proved hypercalciuria and nocturnal polyuria and 10 age matched controls were included in the study. A 24-hour urine collection was performed in 8 sampling periods for measurement of urinary sodium excretion. Segmental tubular sodium transport was investigated during a daytime oral water load test and calculated according to standardized clearance methodology. RESULTS: The children with enuresis showed a marked increase in the fractional excretion of sodium during the night (0.93% +/- 0.36%), while daytime sodium excretion was decreased (0.84% +/- 0.23%). Analysis of segmental tubular sodium transport revealed decreased delivery of sodium to distal tubule (C(H2O) + C(Na) = 10.7 ml/100 ml glomerular filtration rate), indicating increased proximal tubular sodium reabsorption but also stimulation of distal sodium reabsorption as demonstrated by increased fractional distal sodium reabsorption (92.9% +/- 2.2%, controls 90.5% +/- 2.9%). Increased distal reabsorption was associated with increased fractional potassium excretion (17.5% +/- 2.7%, controls 13.6% +/- 6.4%), indicating increased distal tubular sodium/potassium exchange. CONCLUSIONS: No intrinsic defect in renal tubular sodium transport was found, but during the day increased sodium reabsorption in proximal and distal tubules was observed, suggesting extrarenal factors to be involved in altered circadian variation in solute and water excretion by the kidney.

Effect of carbamazepine on urinary volume and osmolality, water clearance, and serum osmolality in patients with primary enuresis.

OBJECTIVE: In this study we investigate the effects of carbamazepine (CBZ) on urinary volume, frequency of micturition, serum and urine osmolality, osmotic and creatinine clearance, and free water clearance in patients with primary nocturnal enuresis. This information might help in our understanding of the mechanism of action of CBZ in management of patients with enuresis. PATIENTS AND METHODS: The study comprised eight patients with primary enuresis (age range, 8-14 yr) who wet at night on a daily basis. Enuretics were given, CBZ 200 mg each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes, osmotic clearance, fractional excretion of sodium, and free water clearance were assayed before CBZ treatment and after 15 d of treatment. Frequencies of bed-wetting and dry nights were observed during treatment. RESULTS: Mean number (+/-SD) of dry nights was increased from zero dry nights (daily bed-wetting) to 9.7 (2.8) per 15 d of treatment (65%). CBZ decreased the 24-h urinary volume by 41%, the night volume by 45%, the day volume by 38%, and frequency of micturition by 28%. CBZ increased the 24-h urinary osmolality by 43%. Serum osmolality changed significantly from 283.7 mOsm/l to 277.2 mOsm/l. CBZ decreased osmotic clearance by 37% and free water clearance by 34%. Creatinine clearance was decreased by 19% after CBZ treatment (p < 0.05). CONCLUSION: CBZ reduced urine volume, increased urine osmolality, and decreased the free water clearance, the osmotic clearance, and the frequency of micturition in enuretics; this might help in understanding its mechanism of action.

Oral ddAVP for nighttime urinary incontinence in characterized nursing home residents: a pilot study.

OBJECTIVES: To (1) identify abnormalities in arginine vasopressin (AVP, a water-conserving hormone) secretion and release in nursing home (NH) residents with nighttime urinary incontinence (UI); and (2) perform a pilot test of desmopressin acetate (ddAVP, a synthetic analog of the naturally occurring hormone) replacement in these residents. DESIGN: Diagnostic evaluation and open-label treatment trial. SETTING: Two community nursing homes in a metropolitan area. PARTICIPANTS: Male and female NH residents 65 years of age and older with nighttime UI. INTERVENTION: Characterizations of AVP status followed by a 7-day open-label trial of oral ddAVP (either 0.1 mg or 0.2 mg). MEASUREMENTS: Water deprivation test results, AVP levels, voided volumes, number of voids, incontinent episodes, number of nighttime checks found wet (out of 6 total checks per night). RESULTS: All participants had measurable AVP levels of 2.0 pg/mL or higher. Six of 10 individuals had an abnormal water deprivation test. Two of 4 participants on 0.2 mg of ddAVP and 2 of 6 participants on 0.1 mg had a 200 mL or more mean reduction in nighttime urine volume. Both ddAVP dosages yielded a mean reduction of 0.7 fewer nighttime wet checks found wet. One participant in each group developed hyponatremia (1 of 6 on 0.1 mg and 1 of 4 on 0.2 mg). Hyponatremia resolved with discontinuation of the drug. CONCLUSION: Both 0.1 mg and 0.2 mg of ddAVP given to carefully screened NH residents for 7 days produced a modest average reduction in nighttime urine volume and number of nighttime incontinent episodes that is likely of little clinical importance. The role of ddAVP in this population requires further research.

Adrenomedullin and nitrite levels in children with primary nocturnal enuresis.

Primary nocturnal enuresis (PNE) is the most common type of nocturnal enuresis in children, but its etiology remains unclear. Recent studies indicated the differences in urinary electrolytes in enuretic children, and stressed the existence of a renal tubular maturation defect. In this study, 30 children (aged 6-12 years) with PNE were investigated in comparison with 18 healthy controls. We evaluated plasma antidiuretic hormone, electrolytes, 24-h urine volume, osmolarity, and urinary electrolytes. Unlike other studies, we firstly assessed the plasma and urinary adrenomedullin (AM) and total nitrite levels, a stable product of nitric oxide (NO), and investigated their relationship with urinary electrolytes. The plasma AM and total nitrite levels were significantly lower than controls. Urine volume (24-h) and potassium excretion were higher than in controls. However, 24-h urinary osmolarity and excretion of AM were significantly lower than in controls. Our results indicate that there may be a problem in renal regulation of potassium in children with PNE. Although decreased levels of AM and total nitrite may be a compensatory response to abnormal potassium and water excretion, further investigations are required to exclude whether the renal synthesis of AM and NO are also deficient in these children.

Enuresis.

The authors do not have all of the data about enuresis, and many children are subject to relapses or failure of treatment. There is no cause for despondency, however. Enuresis is no longer a mystery. Good data exist about the natural history, epidemiology, and etiology of enuresis. In addition, multiple treatment modalities are available to practitioners. This article has sought to review the scientific literature and to relate the authors' experience with enuresis. The authors recommend a treatment program for children with monosymptomatic nocturnal enuresis that includes removal of caffeine from the diet. Enuretic children do not consume enough fluid, and the authors recommend that the daily fluid requirement be divided during the day: 40% in the morning, 40% in the afternoon, and 20% in the evening, with no restriction of fluid. Normalization of small functional bladder capacities may help to cure enuresis and has an effect on the efficacy of other therapies. Treatment of enuretics with antibiotics is effective in children with UTI, bacteriuria, or cystitis cystica. DDAVP has been shown to be effective in the treatment of enuresis, especially in children who have achieved a normal functional bladder capacity. Bladder alarm systems also offer a potential cure of enuresis, are inexpensive, and show a low relapse rate.

Melatonin production is similar in children with monosymptomatic nocturnal enuresis or other forms of enuresis/incontinence and in controls.

PURPOSE: Monosymptomatic nocturnal enuresis is a disorder, the precise etiology and pathomechanism of which remain unknown. An elevated sleep arousal threshold leading to deep sleep, and an amplitude disturbance in circadian arginine vasopressin secretion and urine production have been suggested as possible causes of the disease. The pineal hormone melatonin is allegedly implicated in the physiological sleep mechanism and circadian system. Melatonin serum levels are high at night and low during the day. The major metabolite of melatonin, 6-hydroxy-melatonin-sulfate (aMT6s), is excreted in the urine and is a good indicator of its production. We explore whether alterations in melatonin secretion assessed by its aMT6s excretion might be implicated in the pathomechanism of monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: Urine was collected for 24-hour periods from 44 children with monosymptomatic nocturnal enuresis, 10 children with other forms of enuresis/incontinence (nonmonosymptomatic nocturnal enuresis) and 25 controls, and its aMT6s concentration was estimated using a commercially available radioimmunoassay. The total amount of aMT6s excreted per day was calculated. RESULTS: We found no significant differences in the amount of aMT6s excreted in a 24-hour period among patients with or without monosymptomatic nocturnal enuresis and controls with values of 17.6 microg. (1st to 3rd percentile 10.0 to 27.8) versus 13.4 (9.1 to 19.6) versus 21.5 (13.5 to 31.4), respectively. If aMT6s excretion was related to body weight, the result did not change. CONCLUSIONS: Our data do not indicate that alterations in melatonin production might be involved in the elevation of the sleep arousal threshold associated with deep sleep in children with monosymptomatic nocturnal enuresis.

Decreased nocturnal urinary antidiuretic hormone excretion in enuresis is increased by imipramine.

OBJECTIVE: To assess the role of integrated nocturnal antidiuretic hormone (ADH) secretion in children with enuresis, and possible modifications induced by treatment with imipramine. PATIENTS AND METHODS: The morning plasma ADH and nocturnal urinary ADH integrated concentrations were measured in 18 consecutive enuretic children (patients) and 21 age- and sex-matched controls admitted for minor treatment. Diurnal and nocturnal urine production, and plasma and urinary osmolality were also determined; lumbosacral radiography and uroflowmetry were undertaken in the patients. The assessments were repeated after 14 days of treatment with imipramine hydrochloride (orally, 20 mg/night). RESULTS: Half the patients had occult spinal malformations but the uroflowmetry results were all within the normal range. The median (95% confidence interval, CI) urinary ADH integrated concentrations were markedly lower in patients, at 29.7 (22.1-37.3) vs 63.0 (35.1-90.8) pg/mL/h (P = 0.03) than in controls. Plasma ADH levels were significantly increased by imipramine (0.64 to 1.47 pg/mL, 95% CI, 0.40-0.89 vs -0.26-3.2; P < 0.001), as were nocturnal urinary ADH integrated concentrations, at 29.7 (22.1-37.3) vs 59.0 (37.3-80.6) pg/mL/h (P < 0.001), and morning plasma osmolality decreased, from 298.5 (294.5-302.5) to 294.9 (292.4-297.3) mosmol/kg (P = 0.003), as was the 24-h fluid intake, from 983 (721-1245) to 666 (435-897) mL (P = 0.004). CONCLUSIONS: We conclude that enuretic children have a lower nocturnal ADH excretion; imipramine restores nocturnal ADH excretion, increases morning plasma ADH levels, and causes consistent changes in other biochemical variables.

Osmoregulation and desmopressin pharmacokinetics in enuretic children.

OBJECTIVE: The aim was to compare responders and nonresponders to antienuretic treatment with desmopressin with respect to pharmacokinetics and renal effects of the drug. METHODS: Twelve children, aged 7.6 to 16.2 years, with nocturnal enuresis were examined. Six patients were nonresponders and 6 were responders to desmopressin treatment. The children were given 2 mg of desmopressin intravenously and plasma concentrations of the drug were monitored overnight. Urine parameters were followed for 24 hours after desmopressin administration. Ten patients also underwent a thirst provocation test. RESULTS: Desmopressin pharmacokinetics did not differ between the groups. Neither nocturnal urine production nor morning urine osmolality after desmopressin injection differed between responders and nonresponders, whereas the responders produced significantly larger amounts of significantly less concentrated urine during the day after the injection compared with the nonresponders (urine production, 2.02 +/- 0.84 and 0.77 +/- 0.20 mL/kg/h; urine osmolality, 558 +/- 271 and 883 +/- 134 mOsm/kg). Nonresponders voided with smaller bladder volumes (2.43 +/- 0.68 mL/kg body weight) than responders (4.70 +/- 1.21 mL/kg). The responders produced significantly less concentrated urine than the nonresponders during the thirst provocation test (607 +/- 185 and 922 +/- 217 mOsm/kg, respectively). CONCLUSION: Intravenous desmopressin pharmacokinetics and desmopressin renal effects did not differ between responders and nonresponders to desmopressin treatment. Nonresponders had a smaller spontaneous bladder capacity and responders produced less concentrated urine.

Desmopressin versus indomethacin treatment in primary nocturnal enuresis and the role of prostaglandins.

OBJECTIVES: To compare the efficacy of desmopressin and indomethacin and also determine the prostaglandin E2 (PGE2) concentrations in the patient and control groups. METHODS: Eighty-five children with primary nocturnal enuresis were followed up for a baseline period of 4 weeks, during which they recorded wet and dry nights. After this period, the patients were divided into three groups that used desmopressin, indomethacin, or placebo for 4 weeks. The dosage of desmopressin (group A, n = 31 ) was 20 microg/day and the dosage of indomethacin (group B, n = 29) was 100 mg/day. The placebo group (group C) consisted of 25 patients. We determined the serum PGE2 and urine PGE2 concentrations before and after treatment in the three groups and in a control group. RESULTS: Treatment with desmopressin and indomethacin resulted in significantly more dry nights during the 4 weeks of observation than did placebo (P <0.005). The number of dry nights was also significantly different in the desmopressin group than in the indomethacin group (P <0.01). In the total patient group, the mean serum and urine PGE2 concentrations were significantly different from the control group's serum and urine PGE2 concentrations (P <0.001). There was a significant decrease in the serum and urine PGE2 concentrations in group A and group B after the treatment period (P <0.01). CONCLUSIONS: Desmopressin and indomethacin were found to be more effective than placebo. We conclude that prostaglandins have an important role in the pathophysiology of primary nocturnal enuresis.

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.

Renal functions of enuretic and nonenuretic children: hypernatriuria and kaliuresis as causes of nocturnal enuresis.

OBJECTIVE: The aim of this study was to investigate the pathophysiologic cause(s) of primary nocturnal enuresis. Therefore, electrolyte concentrations of urine specimens were evaluated in the morning, and alterations compared between enuretics and nonenuretics. METHODS AND PATIENTS: First morning urine specimens of 27 enuretics and 21 nonenuretic subjects fed the same diet were collected, and urinary electrolytes were measured. The urinary Ca/Cr ratio, tubular reabsorption of phosphorus (TRP) and fractional sodium (FE Na%) and potassium excretions (FE K%) were determined for patients and controls. RESULTS: There was no significant difference in the Ca/Cr ratio and TRP between patients and controls, but enuretic patients had significantly higher FE Na% and FE K% values than controls (p < 0.001). There were significant positive correlations between FE Na% and (r = 0.81, p < 0.001) FE K% and the frequency of bedwetting, respectively, among enuretic patients (r = 0.54, p < 0.001). CONCLUSION: Since Na and K excretion of enuretic patients was higher than in nonenuretics, it can be concluded that there may be a benign hereditary and/or postural renal tubular handling disorder of Na and K in enuretic children.

[Endocrine theory of idiopathic nocturnal enuresis]. / La théorie endocrinienne de l'énurésie nocturne idiopathique.

Body fluid homeostasis is maintained by the kidney. Such an accurate control in achieved via the secretion of antidiuretic hormone (ADH), the secretion of which is regulated by hypothalamic osmoreceptors. Both urine flow rate and the excretion of most electrolytes have a diurnal rhythm; they increase during daytime and decrease during nighttime. Such a rhythm seems to be absent in some subjects who suffer from bedwetting because of relative polyuria. In these cases, the polyuria is associated with a decreased nocturnal secretion of ADH and the subsequent excretion of dilated urine. A deficit in the nocturnal secretion of ADH thus appears to explain the response to desmopressin of children with a polyuric form of enuresis.

[Nocturnal enuresis as a manifestation of autocoidosis]. / Nochnoi énurez kak proiavlenie autacoidoza.

The study entered 30 children with nocturnal enuresis and 20 healthy controls aged 6-15 years. The enuretic children had a higher night diuresis and free water reabsorption; there was an increase in nocturnal excretion of sodium, calcium and magnesium ions. Before going to bed the patients received diclofenac-sodium. Inhibition of cyclooxygenase and decrease of prostaglandin production led to normalization of diuresis and natriuresis, elimination of nocturnal enuresis episodes. The evidence has been obtained that nocturnal enuresis is accompanied by an increased production of autocoids in the thick ascending Henle loop and, as a result, of an increase in saluresis and diuresis. It is suggested that there is a form of nocturnal diuresis which depends on a local hyperproduction of autocoids. The problem of autocoids role in the internal medicine is discussed.

Platelet plasma membrane in subjects with primary nocturnal enuresis: effect of desmopressin.

Plasma membrane fluidity of platelets (PLT) obtained from subjects with primary nocturnal enuresis (PNE) and healthy controls was investigated before and after addition of desmopressin (DDAVP). Membrane fluidity was studied by measuring steady-state fluorescence anisotropy of 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3, 5-hexatriene incorporated into PLT plasma membrane. Our results show an increase in membrane fluidity at the surface level of PLT from subjects with PNE. Moreover, the addition of DDAVP induces a stable and significant decrease of membrane fluidity in both groups. These results suggest alterations of the lipid order in the exterior part of the PLT plasma membrane from patients with PNE.

A pharmacodynamic study of desmopressin in patients with nocturnal enuresis.

The pharmacokinetics of desmopressin (1-desamino-8-D-arginine vasopressin) were investigated in 8 patients with nocturnal enuresis, of whom 4 were known to respond completely to desmopressin and 4 were nonresponders. A decrease in urine production was confirmed in responders after the administration of desmopressin while the drug did not cause antidiuresis in nonresponders. Absorption and excretion of desmopressin were identical in each group. Results indicate at least 2 pathophysiological mechanisms in nocturnal enuresis, including insufficient nocturnal production of arginine vasopressin and impaired renal sensitivity to arginine vasopressin and desmopressin. Each type results in high nocturnal urine production.

Plasma and urinary levels of vasopressin in enuretic and non-enuretic children.

Plasma and urinary levels of vasopressin were measured by radioimmunoassay in 18 children with primary nocturnal enuresis and 20 age and sex matched controls. All subjects followed a protocol whereby all urine were collected and divided up into daytime (8 a.m.-8 pm) and night-time (8 p.m. - 8 a.m.) samples. Urine osmolality and urinary vasopressin levels were measured and, following an overnight observation period, the following morning (8 a.m.) plasma vasopressin was measured. Plasma vasopressin was significantly lower in the enuretic group (2.86 +/- 0.44 pg/ml) compared to the control group (3.64 +/- 1.35 pg/ml) (p = 0.011). Total urinary vasopressin excretion over 24 hours was lower in the enuretic group but the difference was not significant. These results support the hypothesis that one of the factors responsible for nocturnal enuresis in children may be due to a reduced nocturnal secretion of vasopressin. This may explain why the vasopressin substitution therapy is able to successfully abolish nocturnal enuresis symptoms.