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S Rittig

Publications and source records attributed to S Rittig.

At least 19 recordsLinked to original sources
PubMed2002

The relationship between desmopressin treatment and voiding pattern in children.

OBJECTIVE: To collect data on voiding patterns at baseline (no treatment) and during short-term desmopressin treatment, with special reference to the functional and the mean bladder capacity. PATIENTS AND METHODS: The study included 120 children (aged 6-16 years) with monosymptomatic nocturnal enuresis. While at home they recorded their fluid intake and diuresis in two separate periods, i.e. 2 weeks as a baseline registration and another 2 weeks during desmopressin titration. On four study days the children recorded the time and volume of all voids and of fluid intake. From the diaries their functional and mean bladder capacities, 24-h diuresis and day/night ratio of diuresis were determined. RESULTS: The mean 24-h diuresis was significantly lower during short-term desmopressin treatment. In most of the enuretics the mean day/night ratio increased on desmopressin treatment. The mean functional and mean bladder capacities were unaffected by desmopressin. Those not responding had bladder capacities of approximately 100 mL less than full responders. Regardless of response, practically all the enuretics in the study had a smaller functional bladder capacity than expected for their age. Among responders the morning void was significantly larger than the following voids during the day, and among non-responders the fourth void was significantly larger than the previous voids in the day. Desmopressin treatment did not influence these volumes significantly. CONCLUSIONS: Short-term desmopressin treatment does not affect functional and mean bladder capacity; 24-h urine production was reduced significantly (P<0.01) during desmopressin treatment.

Adolescent↗
PubMed2001

A new mutation of the arginine vasopressin-neurophysin II gene in a family with autosomal dominant neurohypophyseal diabetes insipidus.

Familial neurohypophyseal diabetes insipidus (FNDI) is an autosomally dominant inherited disorder with a typical onset at one to six years of age. The genetic locus of FNDI is the arginine vasopressin-neurophysin II (AVP-NPII) gene. The gene encoding the precursor hormone (prepro-AVP-neurophysin II) is located in the chromosomal region 20p13 and contains three exons. Mutations that cause FNDI have been found to occur within the signal peptide of the prepro-AVP-neurophysin II precursor, within the coding sequence for neurophysin II and the vasopressin-coding sequence. A family (four members with FNDI, two without FNDI) in three consecutive generations was investigated. Index case was a now 22-year old man with a history of severe polyuria (18 L/day) and polydipsia first recognized at about 4-5 months of age. The arginine vasopressin-neurophysin II gene was investigated by direct sequencing of PCR products amplified from each exon. Subsequently, a restriction analysis was performed to verify the sequencing results. The affected individuals were found to have a missense mutation in exon 2 at nucleotide position 1887 (G to C) of the AVP-NPII gene. Using both restriction enzyme digestion and sequence analysis, the mutation was found in all affected family members, but not in the unaffected members studied. This mutation (1887 G to C) represents a novel mutation of the AVP-NPII gene.

Adult↗
PubMed2001

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.

Adolescent↗
PubMed2001

The genetics of enuresis: a review.

PURPOSE: Formal studies of the genetics of enuresis have been performed since the 1930s and molecular genetics since 1995, both highlighting the importance of hereditary factors in the etiology of nocturnal enuresis. We summarize the current state of knowledge with respect to the genetics of nocturnal enuresis and its genotype-phenotype interactions. MATERIALS AND METHODS: A comprehensive review of the published data available on the genetic basis of enuresis was performed. RESULTS: Genetic factors are the most important in the etiology of nocturnal enuresis but somatic and psychosocial environmental factors have a major modulatory effect. Most commonly, nocturnal enuresis is inherited via an autosomal dominant mode of transmission with high penetrance (90%). However, a third of all cases are sporadic, and the difference between sporadic and familial forms is not known. Four gene loci associated with nocturnal enuresis have been identified but the existence of others is presumed (locus heterogeneity). All likely candidate genes have been excluded so far. There is no specific association among the different loci, type of wetting and other aspects of the phenotype. All subtypes of nocturnal enuresis (primary, secondary, combined day/night wetting) are susceptible to comparable genetic influences. Certain syndromes of day wetting follow their own genetic mechanisms but this association with the genetics of nocturnal enuresis is not known. CONCLUSIONS: Nocturnal enuresis is a common, genetic and heterogeneous disorder. The associations between genotype and phenotype are complex and are susceptible to environmental influences. Therefore, exact assessment of the clinical phenotype and identification of intermediary phenotypes or traits are needed. Future research will focus on the identification of genes, gene products and their interaction with environmental factors.

Child↗
PubMed2001

Linkage study of a large Danish 4-generation family with urge incontinence and nocturnal enuresis.

PURPOSE: We studied a large 4-generation family in which night and day voiding problems segregated in an autosomal dominant pattern with a high penetrance. We mapped the gene(s) causing these forms of incontinence using a total genome scan approach. MATERIALS AND METHODS: The family comprises 74 subjects in 4 generations. The clinical phenotypes were evaluated by detailed questionnaires and frequency volume charts. Genetically, a genome scan approach with 500 polymorphic marker systems was used to localize a chromosome area for the trait(s) and to narrow down a candidate region. The 3 different genetic models studied were 1) a single gene causing either day, night or day and night incontinence; 2) a gene primarily causing night incontinence; and 3) 2 different genes each causing only day or night incontinence. RESULTS: For model 2 we found 2 areas that gave a high lod score on 2-point analysis (D4S2960, 4p16.1, Z = 3.66 and D12S86, 12q24.2, Z = 3.22) on chromosome 4p and 12q. With an estimated penetrance of 75% only 4p linkage was significant. Models 1 and 3 were excluded as causes due to lack of the affected haplotype in affected subjects. Based on manual haplotype and 2-point analyses, all other areas were excluded for linkage. CONCLUSIONS: The most likely genetic model in this kindred seems to be a gene located on chromosome 4p16.1 causing primarily nocturnal enuresis. However, involvement of chromosome 12q24.3 cannot be excluded for linkage. The dopamine receptors DRD5 and D1B are mapped to chromosome 4p16. These genes are candidate genes for nocturnal enuresis and urge incontinence.

Child↗
PubMed2001

No relationship between family history of enuresis and response to desmopressin.

PURPOSE: We determined the prevalence of positive family history of nocturnal enuresis in relation to response to desmopressin. MATERIALS AND METHODS: A total of 328 children with nocturnal enuresis and 53 normal children were interviewed to determine the presence of family history of nocturnal enuresis. Response to desmopressin was confirmed in some cases by home recordings of enuresis episodes during 2 baseline weeks and 2 weeks of 20 to 40 microg. desmopressin intranasally. RESULTS: Significantly more patients than normal children (75% versus 38%, p <0.001) reported a positive family history of enuresis (any relative). The high prevalence of a positive family history of nocturnal enuresis was present in severe/nonsevere or primary/secondary types of enuresis. Of the patients 141 completed 4 weeks of home recordings including 20 with a complete response (greater than 90% reduction in wet nights week), 25 with a partial response (50% to 90% reduction) and 96 with no response (less than 50% reduction). The prevalence of a positive family history (any relative) was no different among the response groups (80%, 84% and 78%, respectively). Similarly, family history, as defined by first order relatives only, showed no relation to treatment response. CONCLUSIONS: A positive family history of nocturnal enuresis is more prevalent in patients with enuresis than in normal children regardless of the nature of the nocturnal enuresis. In contrast to previous reports, a positive family history failed to predict a good response to desmopressin treatment. Hereditary factors are important to consider in desmopressin responding and desmopressin resistant cases.

Adolescent↗
PubMed2001

Intra-individual variability in nighttime urine production and functional bladder capacity estimated by home recordings in patients with nocturnal enuresis.

PURPOSE: We evaluated the intra-individual variability and reproducibility of nighttime urine production on wet nights and functional bladder capacity estimated by long-term home recordings of monosymptomatic nocturnal enuresis. In particular, the intention was to evaluate the validity of 1 versus 2 weeks of recording when estimating urine volume on wet nights and 1 versus 2 weekends of recording when estimating functional bladder capacity. MATERIALS AND METHODS: We analyzed 120, 2-week home recordings of nighttime urine volume from patients with monosymptomatic nocturnal enuresis 6 to 16 years old (mean age 9.1) with at least 3 wet nights per week. Most patients were nonresponders or partial responders to desmopressin. Nighttime urine volume was estimated by weighing diapers before and after sleep, and measuring morning urine volume. Of the home recordings 62 included frequency volume charts for 2 weekends, which were evaluated for functional bladder capacity defined as the largest voided volume observed. RESULTS: No significant overall week-to-week differences were observed in average urine volume on wet nights and functional bladder capacity. There was a large intra-individual variability in all measured variables, which was most pronounced for functional bladder capacity and least pronounced for urine volume on wet nights. With regard to repeatability, the limits of agreement of urine volume on wet nights were -32% and 36% (95% confidence interval) as opposed to -54% and 48% for functional bladder capacity. CONCLUSIONS: In this study intra-individual week-to-week estimates of average urine volume on wet nights demonstrated acceptable variability and repeatability in contrast to functional bladder capacity. A reliable estimate of urine volume on wet nights could be obtained by 7 nights of home recording, whereas 4 days of daytime recording were necessary when estimating functional bladder capacity. Similar studies of patients who respond to desmopressin are needed.

Adolescent↗
PubMed2000

A novel splicing mutation in the V2 vasopressin receptor.

In order to elucidate the molecular basis and the clinical characteristics of X-linked recessive nephrogenic diabetes insipidus (CNDI) in a kindred of Danish descent, we performed direct sequencing of the arginine vasopressin receptor 2 (AVPR2) gene in five members of the family, as well as clinical investigations comprising a fluid deprivation test and a 1-deamino-8-D-arginine-vasopressin (dDAVP) infusion test in the study subject and his mother. We found a highly unusual, novel, de novo 1447A-->C point mutation (gDNA), involving the invariable splice acceptor of the second intron of the gene in both the affected male (hemizygous) and his mother (heterozygous). This mutation is likely to cause aberrant splicing of the terminal intron of the gene, leading to a non-functional AVP receptor. The clinical studies were consistent with such a hypothesis, as the affected subject had a severe insensitivity to both the antidiuretic and the coagulation factors stimulatory actions of AVP and its analogue dDAVP. Direct sequencing of the AVPR2 is an accurate and rapid diagnostic tool for CNDI and early referral of patients for AVPR2 sequencing is therefore strongly suggested.

Alternative Splicing↗
PubMed1999

Nocturia and polyuria in men referred with lower urinary tract symptoms, assessed using a 7-day frequency-volume chart.

OBJECTIVES: To investigate if a 7-day frequency-volume (FV) chart could identify nocturia on a polyuric basis in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study included 23 patients (mean age 62.8 years, range 42-78) with LUTS who were referred for the evaluation of potential BPH and 11 men (control subjects, mean age 63.3 years, range 58-69); all completed a 7-day FV chart investigation as outpatients. RESULTS: Nocturia was associated with nocturnal polyuria in 10 of 23 patients with LUTS; these 10 patients had a diminished diurnal variation of urine production, whereas 13 patients had a diurnal variation in urine production comparable with that in controls with no nocturia. The degree of nocturia correlated positively with nocturnal urine production but showed no relationship with sleep duration. The nocturnal polyuria in these patients was associated with a higher 24-h urine production and seemed at least partly to be caused by a higher fluid intake during daytime. CONCLUSION: Nocturia on a polyuric basis can be detected by using a FV chart. In these patients, a 3-day FV chart would be sufficient to detect nocturia on a polyuric basis and seems therefore to be a valuable tool in evaluating patients with LUTS referred for potential BPH.

Adult↗
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↗