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The synthetic AVP analogue 1-desamino-8-d-arginine-vasopressin (dDAVP) is used for treatment of polyuric disorders. Lack of commercially available assays limits the usefulness of dDAVP as a diagnostic tool in the assessment of renal concentrating capacity. We aimed to develop a specific radioimmunoassay (RIA) for determination of plasma dDAVP (pdDAVP) in order to investigate the relationship between pdDAVP levels and urine osmolality (Uosm). Further, we aimed to determine the onset, duration, and maximum concentrating capacity following intravenous (i.v.) bolus dDAVP injection. The dDAVP assay was based on a well-established RIA for measurements of AVP. Fourteen healthy subjects (aged 15-18 years) participated. Blood and urine samples were collected prior to and after i.v. bolus of 0.03 µg/kg dDAVP. Diuresis and Uosm was measured for nine hours following dDAVP administration. PdDAVP and Uosm were analyzed.We established a specific RIA for the measurement of pdDAVP. All subjects reached maximal pdDAVP concentration (C max ) 30 minutes following infusion, and a rise in Uosm after 60 minutes. Maximal Uosm varied between subjects, with no direct correlation to the achieved pdDAVP levels. We found no significant intra-individual variation between two dDAVP infusions and the effect was reproducible in terms of C max and maximal Uosm. We characterized the relationship between pdDAVP and Uosm after dDAVP bolus injection in healthy adolescents using our dDAVP assay. Maximal Uosm achieved correlated with the baseline Uosm levels and seemed unrelated to achieved pdDAVP levels. The urine concentrating response was maintained at least eight hours.

Background: Bioelectrical impedance analysis (BIA) requires a high degree of standardisation in order to ensure valid and reproducible impedance measurements. The overall aim of this review was to study the degree to which BIA papers conducted in healthy paediatric populations (aged 0-17 years) were standardised., Methods: Literature was identified on the basis of a systematic search of internationally-recognised electronic databases and hand searching of the reference lists of the included papers in order to identify additional relevant papers. The review was limited to lead-type BIA devices for whole-body, segmental- and focal impedance measurements. In total, 71 papers published between 1988 and 2016 were included. To evaluate the degree of standardisation of the papers, a recently published review detailing critical factors that may impact on BIA measurements in children was used as a model for structuring and extracting data., Results: There was a general lack of BIA standardisation, or its reporting, in the papers under review, which hinders comparison of data between studies and could potentially lead to erroneous measurements., Conclusions: If the BIA technique should be accepted clinically for routine use in paediatric populations, there is a need for an increased focus on the importance of improved standardisation and its reporting in future studies. Consequently, this review contains recommendations for performing and reporting BIA measurements in a standardised manner.

Several guidelines for bioelectrical impedance analysis (BIA) have been prepared for adults, but not for children. For that reason, there is a pressing need to develop a consensus set of guidelines to facilitate standardisation of BIA in this important group. This review provides an introduction to BIA, highlights critical factors that may impact on BIA and identifies areas where there is a need for further research in order to increase the quality of impedance measurements and prediction of body composition in children. Although the results of this review highlights a lack of studies in children to provide definitive BIA guidelines, the technique has, however, still proven valuable for body composition assessment in ill and healthy children. To fill the gaps in our knowledge, future studies should focus on methodological issues, particularly with regard to hydration, voiding, clothing, skin preparation and body position. The review may advantageously be used as a checklist in the planning of future studies. Finally, this review forms the basis for the development of guidelines for BIA assessment in this particular group; a task appropriately to be undertaken by scientific societies within the field.

Objective: To establish the clinical phenotype and genetic background in a family with diabetes insipidus., Material and Methods: The subjects were a sister and brother, aged 34 and 27 years, respectively, with a history of polyuria since infancy. Clinical testing confirmed a diagnosis of congenital nephrogenic diabetes insipidus (CNDI) in both. Samples of purified genomic DNA were analysed., Results: The sequence of the entire coding region of the AQP2 gene as well as the AVPR2 gene was determined. Sequence analysis revealed no variations in the AQP2 gene. A missense variation in exon 2 of the AVPR2 gene (g.685G>A), predicting a p.Asp85Asn substitution, was identified in the X-chromosome of the affected male and one allele in the sister and the asymptomatic mother. The p.Asp85Asn variation in AVPR2 is known to cause CNDI, and has previously been described as inducing a partial phenotype treatable with dDAVP. However, in this family dDAVP had no influence on urine osmolality, whereas combination therapy with indomethacin and hydrochlorothiazide increased urine osmolality to 299 mosm/l in the proband. A skewed X-inactivation pattern (93%) occurring in the normal X allele was recognized in the sister., Conclusions: This study demonstrates the effect of skewed X-chromosome inactivation associated with X-linked CNDI. Polydipsia in early childhood could be due to X-linked CNDI despite affecting both genders. The significant heterogeneity in the clinical phenotype in CNDI carries a risk of diagnostic misinterpretation and emphasizes the need for genetic characterization. Treatment combining indomethacin and hydrochlorothiazide results in a marked response on both urine output and urine osmolality.

Objective: Renal involvement in Henoch-Schönlein purpura (HSP) constitutes a risk of end-stage renal disease (ESRD), especially in patients presenting with nephrotic syndrome., Patients and Methods: The clinical courses of six patients (mean age 13.2 years; four boys and two girls) admitted from 2000 to 2007 with HSP and nephrotic syndrome were reviewed. Average follow-up was 44 months (28-59). Treatment protocols included oral prednisolone and in non-responders cyclosporin A, cyclophosphamide, mycophenolate mofetil or tacrolimus. Five patients were treated immediately after presentation of nephrotic syndrome/nephrotic range proteinuria (median 277 mg/m(2)/h). The last patient was treated locally with low-dose prednisolone (0.2-0.9 mg/kg/day) and 3 months of low-dose cyclophosphamide (1 mg/kg/day)., Results: All five patients treated promptly with high-dose immunosuppressant had normal estimated glomerular filtration rate (eGFR) (median 159 ml/min/1.73 m(2)) at follow-up. One obtained complete remission, two had positive dipstick proteinuria and two needed angiotensin-converting enzyme inhibitors to stay normotensive. The patient receiving low-dose immunosuppression at onset progressed to ESRD 44 months later. At initial presentation eGFR, blood pressure, renal biopsy grading, proteinuric range and plasma albumin were similar in all patients., Conclusion: Follow-up data from the patients suggest that an early aggressive immunosuppressive approach improves long-term renal outcome in HSP patients with nephrotic syndrome.

Objective: To analyse retrospectively the efficacy of day-time incontinence treatment in a secondary referral centre and consider characteristics of responders to the different therapeutic interventions., Material and Methods: All children treated for day-time urinary incontinence at the authors' clinics from 2000 to 2004 were included. Children with ongoing urinary tract infections were excluded. Before treatment, children filled out registrations of incontinence episodes and 48h frequency-volume charts. Faecal disorders were treated before urinary incontinence. All children were subjected to standard urotherapy and were secondarily recommended a timer-watch. If standard urotherapy had no effect, anticholinergics were added., Results: The study included 240 children with day-time urinary incontinence. Of these, 45 had faecal problems and 17% obtained urinary continence when these were successfully treated. In total, 126 (55%) became dry on standard urotherapy. Of the 60 children who had a timer-watch in addition to standard urotherapy, 70% became dry. Of the 62 children who had anticholinergics in addition to standard urotherapy, 81% became continent. Fifteen (6%) did not achieve continence and another 11 patients were lost to follow-up. Children who became dry solely on standard urotherapy had a significantly lower voiding frequency (p<0.05), larger voided volumes as a percentage of those expected for age (p<0.01) and fewer incontinence episodes per week (p<0.05) than children needing anticholinergics., Conclusions: Most children achieve day-time continence solely on standard urotherapy. Children who need anticholinergics to achieve dryness seem to be those with more severe bladder reservoir function abnormalities and symptoms.

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.

Desmopressin responders tend to have a large volume of urine production at night, in contrast to desmopressin refractory patients who often produce normal volumes of urine. Controls and adolescent/adult primary monosymptomatic nocturnal enuretics were included in a study measuring urine volume and plasma vasopressin levels before and during a 24-hour water deprivation test. The results indicate a significantly higher urine production in desmopressin responders when compared with controls and non-responders. Before fluid deprivation, only the nocturnal polyuric patients showed a urine osmolality significantly lower than that of controls and desmopressin non-responders. A significant decrease in the clearance of osmols was evident in the desmopressin refractory group from day to night. All three groups showed a significant increase in plasma vasopressin during fluid deprivation, with polyuric, desmopressin-responding patients showing a lower increase that the non-responders and controls. Plasma vasopressin levels were normal in adolescent and adult enuretics regardless of their response to desmopressin. Moreover, response to fluid deprivation in both polyuric and enuretic patients resulted in a significant decrease in urine output from the first to the second night.

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.

The aim of this study was to investigate linkage of nocturnal enuresis to a locus on chromosome 22 in 35 German families and to analyse associations with the clinical phenotype. One hundred and sixty-seven enuretic children aged 5-11 years were examined using a somatic, psychiatric and psychological diagnostic protocol; a detailed pedigree over three generations was also compiled. Forty-two children (mean age: 8.11 years) were selected for further molecular genetic examination. EDTA blood samples were taken from the patients and 130 relatives, and polymorphisms of the microsatellite markers D22S446, D22S156 and D22S257 on chromosome 22 were analysed. Positive linkage was found in 11 families of 14 children, indicating that 39.3% of families were compatible with linkage to the markers on chromosome 22. The phenotype included primary nocturnal enuresis and combined day and night wetting. The results for chromosome 22, as with previous loci for nocturnal enuresis on chromosomes 8, 12 and 13, support the hypothesis for genetic and clinical heterogeneity.

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.

Fifty-five normal children, aged between 7 and 12 years, were hospitalised for four consecutive nights. On three of these nights, the subjects received 25 ml/kg body weight of fluid prior to bedtime. Such fluid-loading provoked 28 enuresis-like episodes in 17 children, most of which occurred during the first few hours of sleep. The incidence of these enuretic events decreased with increasing age, more boys than girls were affected, there was a statistically significant correlation between total enuresis volume and nocturia volume, and the micturition was frequently incomplete, leaving large volumes of residual urine in the bladder. It was concluded that if nocturnal urine production exceeds bladder capacity, enuresis may be provoked, even in children who do not normally wet the bed. Furthermore, the definition of nocturnal enuresis as a complete emptying of the bladder during sleep may need revision.

The effect of food ingestion on the gastrointestinal absorption and antidiuretic action of oral desmopressin (Minirin, DDAVP) was assessed in 16 healthy volunteers, aged 20-35 years. The gastrointestinal absorption of desmopressin was reduced and delayed if administered with or 90 minutes after a meal, but this did not influence the antidiuretic action of the drug, at least for the first 3 hours following desmopressin administration.

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 objective of the current study was to identify the associations between phenotype and genotype in children with nocturnal enuresis. Of the total of 167 wetting children, aged 5-10 years, without neurological or structural forms of incontinence, 110 were nocturnal enuretics. The examinations included a full psychiatric and psychological assessment, a paediatric and neurological examination, a family history with pedigree, ultrasonography, uroflowmetery, urinanalysis and bacteriology. Children with secondary nocturnal enuresis (n = 28) had a significantly higher rate of behavioural disorders, life events and continuous psychosocial stress than those with primary nocturnal enuresis (n = 82). Of the latter group, children with primary monosymptomatic nocturnal enuresis (n = 50) had an especially low rate of behavioural problems, when in comparison to primary non-monosymptomatic nocturnal enuretics (n = 32). Formal genetics point to a high genetic predisposition to nocturnal enuresis in all subgroups. Linkage studies to markers on chromosomes 8, 12 and 13 demonstrate both clinical, as well as genetic heterogeneity in nocturnal enuresis.

The bioavailability and pharmacokinetics of desmopressin (Minirin, DDAVP) have been studied in elderly males, aged between 55 and 75 years. In a four-way randomised study, subjects received a dose of desmopressin either intravenously (2 micrograms) or orally (200 micrograms) and either at 11 am or 10 pm. Daytime and night-time urine samples were collected both with and without desmopressin treatment. Intravenous doses of desmopressin were observed to have a longer duration of action than when the dose was given orally. These differences in efficacy may be attributable to differences in the bioavailability of desmopressin after intravenous or oral treatment.

An update of the pathogenesis and treatment of monosymptomatic bedwetting is presented. This frequently occurring entity seems to have a multifactorial pathogenesis incorporating arousal disturbances and disturbances to the circadian rhythm of diuresis modulating hormones. It has recently been substantiated that the bladder reservoir function in monosymptomatic bedwetting is normal. This is further underlined by the fact that treatment of instability of the bladder has proven futile. In a substantial part of the monosymptomatic bedwetters the changes in circadian rhythm of antidiuretic hormone can be counteracted by desmopressin diacetate (DDAVP), which abolishes the symptom in more than 2/3 of the patients. Monitoring circadian rhythms of arginine vasopressin (AVP) and treatment with DDAVP have led to increased understanding of the pathogenesis of monosymptomatic bedwetting and opened new fields of investigation.

The circadian variation of plasma atrial natriuretic peptide (ANP) in relation to urinary excretion of sodium (UNa) and potassium (UK) as well as clearance of creatinine (Ccrea) was assessed in 15 juvenile patients with enuresis nocturna and compared with 11 age-, sex-, and weight-matched normal subjects. Normal juveniles showed a highly significant diurnal variation (p less than 0.001) of plasma ANP with diurnal peak levels at midnight (0000 hours) and minimum levels at 0400 hours. Enuretic patients showed a similar diurnal rhythmicity with normal levels during day and night. In normals both UNa and UK showed significant diurnal rhythmicity with a marked reduction from daytime to night-time. Although the total diurnal excretions of UNa and UK were similar to normals, patients with enuresis showed abnormal diurnal variation in both UNa (p less than 0.05) and UK (p less than 0.01). The abnormal circadian rhythm of UNa and UK in enuretics seemed to be caused by abnormal tubular handling as similar abnormalities were found in the fractional excretions and as the circadian variation of Ccrea was normal. Especially during the first hours of sleep (2200 hours to 0000 hours), the patients showed polyuria (230 +/- 138 ml vs 116 +/- 58 ml, p less than 0.01), natriuresis (20.9 +/- 16.3 mmol l-1 vs 10.7 +/- 6.8 mmol l-1, p less than 0.01), and kaliuresis (7.3 +/- 6.3 mmol l-1 vs 3.7 +/- 2.3 mmol l-1, p less than 0.05), despite normal levels of plasma ANP. In conclusion, the study describes the diurnal variation of plasma ANP in relation to urinary excretion of sodium and potassium in a juvenile normal population. Patients with nocturnal enuresis show abnormal diurnal rhythmicity in the urinary excretion of sodium and potassium that is not correlated to the plasma levels of ANP.

The aim of the study was to investigate the relationship between antral and duodenal fasting motor activity in 19 healthy volunteers using a perfused tube assembly with side-holes placed in the distal antrum, second part of the duodenum and in the duodenum near the ligament of Treitz. Registrations were performed until the end of the second duodenal phase III. Eighty-two per cent of the duodenal phases III were preceded by antral activity. The duration of duodenal phase III showed a positive correlation to the preceding number of antral contractions (p less than 0.001) as well as to antral phase III (p less than 0.05), but no correlation to the duration of antral phase III was found. The duration of the migrating motility complex (MMC) showed a positive correlation to the duration of duodenal phase III (p less than 0.05), but no correlation to the preceding number of antral contractions were found. It may be concluded that the level of duodenal activity is very dependent on the preceding antral activity.

Since it has been argued that the spasmolytic effect of glucagon is related to the first 21 N-terminal amino acid residues, and not to the complete molecule, we have compared the effects of glucagon-(1-21)-peptide (G-(1-21) and glucagon on human antroduodenal motility. Glucagon and G-(1-21) were given as bolus injections to 30 healthy volunteers equally allocated into five groups. Each subject received two doses; one was placebo, 0.25, 0.5, 1.0 or 2.0 mg of glucagon, the other was an equimolar doses of G-(1-21) (placebo, 0.175, 0.35, 0.70 or 1.4 mg of G-1-21). The first injection was given during phase II of a migrating motility complex (MMC), and the next during the following phase II. Contractile activity was recorded using an oral tube with one sidehole positioned in the antrum and two in the duodenum. We confirmed that glucagon decreases the number of contractions in the antrum and duodenum and that normal phase II activity was restored within 20-40 minutes proportionally to the amount of the drug given. G-(1-21) did not change antroduodenal motility nor did it affect the phase II pattern in any of the groups. Neither were any side effects encountered. G-(1-21) does not seem to be an alternative to glucagon and other spasmolytic drugs for obtaining relaxation of the antroduodenal area.

To read and analyze manometric tracings from selected biological systems, a computer program was produced using low cost personal computer hardware. The program contains facilities for automatic scoring of contractions, intercontractile intervals (modality) and frequency analysis. This report concerns analysis of two overnight rectal motility recordings in 11 normal teenagers. After A/D conversion of data the developed software offers a set of options i.e. automatized scoring of contraction, detection of intervals between contractions and analytical tools such as histographic presentation of data, and presentation in the time domain. The A/D conversion time and computer analysis time for an 8 hour recording was 15 and 13 minutes, respectively. The analysis of frequency distribution overnight showed for the material as a whole 63% of no activity, 33% of 0-2 contractions x min-1 and 4% of more than 2 contractions x min-1. Modality analysis showed a peak between 15 and 25 seconds. Approximately 30% of the tracings showed accumulated intervals, which were multiples of the peak. No significant correlation was found between the first and second night of observation regarding the number of contractions and maximum frequency overnight. Significant correlation was found for the number of periods with high frequency activity between the two nights (p less than 0.05). Long-term pressure activity can be analyzed using the presented computer-aided method, providing a rapid and objective measurement of classical parameters and access to more in-depth analysis. This actual study of normal overnight rectal activity showed a large inter- and intra-individual variation.

In 8 adult patients with monosymptomatic nocturnal enuresis (age 18-44 years) we twice investigated the circadian rhythm of plasma vasopressin, plasma atrial natriuretic peptide, serum osmolality, serum electrolytes as well as urinary excretion in relation to urodynamic variables. Seven of the patients showed a lack of diurnal rhythmicity in plasma vasopressin at both diurnal studies with no night-time increase. The nocturnal urinary volumes exceeded the bladder capacities with an average of 155%. This was mainly caused by a large excretion of poorly concentrated urine during the first hours of sleep. Although a slight nocturnal peak in plasma atrial natriuretic peptide was found no clear pathophysiological role could be determined for this peptide. It is concluded that the previously established vasopressin production abnormality in juvenile enuresis seems to persist in adult enuretics.

In patients with monosymptomatic enuresis we investigated bladder activity together with electroencephalography during sleep on two consecutive nights. Thirty-one patients were investigated. Enuretic episodes were found to be normal micturitions not related to any specific sleep stage. Except for a very few bladder contractions outside the enuresis episode we did not observe any bladder activity. In the few instances where bladder activity was seen it was not associated with changes in EEG activity. The bladder contractions were all eliminated by pelvic floor activity, and this could be seen without any disturbances of the sleep indicating that voiding can be inhibited without the child waking up.