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S Rittig

Publications and source records attributed to S Rittig.

At least 37 records · Page 2Linked to original sources
PubMed1999

Molecular genetics of nocturnal enuresis: linkage to a locus on chromosome 22.

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.

Child↗
PubMed1999

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.

Adult↗
PubMed1999

Fluid deprivation in enuresis--effect on urine output and plasma arginine vasopressin.

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.

Administration, Intranasal↗
PubMed1999

Clinical and molecular evidence of abnormal processing and trafficking of the vasopressin preprohormone in a large kindred with familial neurohypophyseal diabetes insipidus due to a signal peptide mutation.

The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by postnatal onset of polyuria and a deficient neurosecretion of the antidiuretic hormone, arginine vasopressin (AVP). Since 1991, adFNDI has been linked to 31 different mutations of the gene that codes for the vasopressin-neurophysin II (AVP-NPII) precursor. The aims of the present study were to relate the clinical phenotype to the specific genotype and to the molecular genetic effects of the most frequently reported adFNDI mutation located at the cleavage site of the signal peptide of AVP-NPII [Ala(-1)Thr]. Genetic analysis and clinical studies of AVP secretion, urinary AVP, and urine output were performed in 16 affected and 16 unaffected family members and 11 spouses of a Danish adFNDI kindred carrying the Ala(-1)Thr mutation. Mutant complementary DNA carrying the same mutation was expressed in a neurogenic cell line (Neuro2A), and the cellular effects were studied by Western blotting, immunocytochemistry, and AVP measurements. The clinical studies showed a severe progressive deficiency of plasma and urinary AVP that manifested during childhood. The expression studies demonstrated that the Ala(- 1)Thr mutant cells produced 8-fold less AVP than wild-type cells and accumulated excessive amounts of 23-kDa NPII protein corresponding to uncleaved prepro-AVP-NPII. Furthermore, a substantial portion of the intracellular AVP-NPII precursor appeared to be colocalized with an endoplasmic reticulum antigen (Grp78). These results provide independent confirmation that this Ala(-1)Thr mutation produces adFNDI by directing the production of a mutant preprohormone that accumulates in the endoplasmic reticulum, because it cannot be cleaved from the signal peptide and transported to neurosecretory vesicles for further processing and secretion.

Adolescent↗
PubMed1998

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.

Adolescent↗
PubMed1998

Molecular genetics of nocturnal enuresis: clinical and genetic heterogeneity.

Forty-two children with nocturnal enuresis (27 with primary, 4 with secondary nocturnal enuresis and 11 with combined primary nocturnal enuresis and daytime wetting) were selected retrospectively from a study of 167 consecutive children with enuresis. The aim of the study was to collect formal genetic data, perform molecular genetic linkage-analyses with five microsatellite markers on chromosomes 13q, 12q or 8q and specify the associations between genetic findings and clinical, as well as psychiatric diagnoses. Positive linkage of nocturnal enuresis to one of the microsatellite markers was possible in 27 children from 23 families and was not possible in 15 children. Somatic findings in both the groups with and without possible assignment of nocturnal enuresis to a marker were heterogeneous. Psychiatrically, a low rate of behavioural problems was apparent. These findings support the hypothesis of genetic and phenotypical heterogeneity of nocturnal enuresis, without linkage of specific psychiatric and somatic phenotypes to certain chromosome markers.

Child↗
PubMed1998

Current trends, diagnosis, and treatment of enuresis.

This survey describes the evolution of our concept of monosymptomatic bedwetting over the last decades. It takes you briefly through psychology and enuresis. The minor role of bladder pathology is described ending up with focusing on the mismatch between bladder capacity at night-time and urine production. Monosymptomatic bedwetting should currently be regarded as an umbrella diagnosis allocated to children where daytime urinary problems have been excluded. Within the diagnosis of monosymptomatic bedwetting we can nowadays identify at least two groups. One is related to children who have a large night-time urine production and a normal bladder capacity, and the other is related to children who have a large night-time production, but a bladder capacity too small for the normal urine production. The genetic aspects are currently investigated. The results and this kind of research will probably end up in a further subgrouping.

Deamino Arginine Vasopressin↗
PubMed1998

Effect of food intake on the pharmacokinetics and antidiuretic activity of oral desmopressin (DDAVP) in hydrated normal subjects.

OBJECTIVE: The effect of food ingestion on the gastrointestinal absorption and antidiuretic action of oral desmopressin. An oral preparation of desmopressin, a synthetic analogue of vasopressin, has recently become available for clinical use. DESIGN: A randomized, single-blind, crossover study with four treatment arms. Day A, no meal + placebo; B, no meal + 400 micrograms oral desmopressin; C, standard meal + 400 micrograms oral desmopressin; D, standard meal + 400 micrograms oral desmopressin after 1.5 hours. Plasma desmopressin was measured every 15-30 minutes for 6 hours after drug intake. An intravenous hydration regimen was employed on each study day. SUBJECTS: Sixteen healthy, non-smoking, mean aged 20-35 years (mean 27.8 years). MEASUREMENTS: Plasma desmopressin concentrations were measured throughout each study day to calculate the area under the desmopressin plasma-concentration-time curve to infinity (AUCinf), the maximum plasma desmopressin concentration (Cmax), the time at which Cmax was reached (Tmax) and the time at which plasma desmopressin was first detected (Tlag). Urine volume, urine osmolality and plasma sodium concentrations were also measured at specified times on each study day. RESULTS: The total absorption of oral desmopressin, reflected by the AUCinf, was significantly higher when taken during the fasting state (day B) compared with its administration with or 1.5 hours after a standard meal (days C and D). In addition, Cmax was higher and both Tmax and Tlag were shorter on day B compared with days C and D. No effect of food ingestion was observed on the pharmacodynamics of oral desmopressin: urine volume was decreased and urine osmolality was increased to similar extents on all active treatment days (B, C and D). No significant reductions in plasma sodium concentrations (a safety parameter) was observed during the trial. CONCLUSIONS: The gastrointestinal absorption of desmopressin is reduced and delayed if administered with or 1.5 hours after a meal. This decreased absorption of desmopressin did not have an impact on the antidiuretic action of the drug since all treatment regimens elicted a maximal response. It is possible that administration of desmopressin in the fasting state may prolong its duration of action.

Administration, Oral↗
PubMed1997

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.

Adolescent↗
PubMed1997

Clinical enuresis phenotypes in familial 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.

Chi-Square Distribution↗
PubMed1997

The enuretic episode--a complete micturition from a bladder with normal capacity? A critical reappraisal of the definition.

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.

Child↗
PubMed1997

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.

Administration, Intranasal↗
PubMed1997

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.

Adult↗
PubMed1997

Desmopressin tablet treatment: factors influencing gastrointestinal absorption.

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.

Absorption↗
PubMed1997

Bioavailability and pharmacokinetics of desmopressin in elderly men.

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.

Administration, Oral↗
PubMed1996

Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus.

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant disorder characterized by progressive postnatal deficiency of arginine vasopressin as a result of mutation in the gene that encodes the hormone. To determine the extent of mutations in the coding region that produce the phenotype, we studied members of 17 unrelated kindreds with the disorder. We sequenced all 3 exons of the gene by using a rapid, direct dye-terminator method and found the causative mutation in each kindred. In four kindreds, the mutations were each identical to mutations described in other affected families. In the other 13 kindreds each mutation was unique. There were two missense mutations that altered the cleavage region of the signal peptide, seven missense mutations in exon 2, which codes for the conserved portion of the protein, one nonsense mutation in exon 2, and three nonsense mutations in exon 3. These findings, together with the clinical features of FNDI, suggest that each of the mutations exerts an effect by directing the production of a pre-prohormone that cannot be folded, processed, or degraded properly and eventually destroys vasopressinergic neurons.

Arginine Vasopressin↗