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Søren Rittig

Publications and source records attributed to Søren Rittig.

18 recordsLinked to original sources
PubMed2006

[Secondary pseudohypoaldosteronism in neonates due to pyelonephritis and congenital urinary tract malformations].

We report two cases of neonates with secondary pseudohypoaldosteronism due to pyelonephritis and congenital urinary tract malformations. Both patients presented with failure to thrive, dehydration, severe hyponatraemia and metabolic acidosis. One of the patients also developed severe hyperkalaemia. Secondary pseudohypoaldosteronism may resemble congenital adrenal hyperplasia. Early diagnosis is essential since both conditions, when untreated, are fatal, and treatment of the two differs significantly. Differential diagnosis may be achieved by acute analysis of urine culture and renal ultrasonography.

Diagnosis, Differential↗
PubMed2006

[Prenatal diagnosed hydronephrosis and other urological anomalies].

By renal ultrasound examination, urological anomalies may be demonstrated in 1-2% of fetuses and in about 0.5% of newborns. Boys have about twice the frequency of girls. Surgical treatment is indicated in about one fourth of these urological anomalies. If all pregnant women in Denmark were to have fetal ultrasound examination of the kidneys and the urinary tract, about 70 children would be born each year with a prenatally diagnosed urological anomaly for which surgical procedure is or will be indicated. This paper provides Danish guidelines for prenatal diagnosis, follow-up and intervention in cases of urological anomalies and guidelines for post-natal diagnosis, follow-up and treatment of these anomalies, especially hydronephrosis.

Abnormalities, Multiple↗
PubMed2006

Nocturia and circadian blood pressure profile in healthy elderly male volunteers.

PURPOSE: Nocturia is attributed to nocturnal polyuria and/or decreased functional bladder capacity. In this study we elucidated the mechanisms behind circadian fluid regulation and the occurrence of nocturia in healthy elderly males, specifically to determine the role of urine output and regulating hormones, blood pressure, and average voided volumes. MATERIALS AND METHODS: A total of 18 males 55 to 73 years old (mean age 61.1) were included in the study. Voiding habits were assessed by completion of a 7-day frequency volume chart recording all fluid intake and voiding. The subjects subsequently underwent inpatient circadian studies measuring the diurnal rhythm of blood pressure, vasopressin, atrial natriuretic peptide, angiotensin II, aldosterone and urine volume. RESULTS: Of the nightly home recordings 25% showed nocturia, characterized by a higher 24-hour and nighttime urine volume. During the inpatient studies 12 of the 18 participants experienced a nocturnal void. Nocturia nights were characterized by significantly decreased day-to-night ratios in urine output and a higher nighttime mean arterial blood pressure. A circadian variation in plasma arginine vasopressin was seen only in the group without nocturia. The other hormones revealed a circadian rhythm similar in the 2 groups. CONCLUSIONS: In healthy males with occasional nocturia, the occurrence of nocturia seems to be associated with a blunting of the circadian rhythm of diuresis and increased arterial blood pressures during the night. These findings may implicate a role for a baroregulatory related mechanism in nocturia.

Aged↗
PubMed2006

Reproducibility of contrast enhanced magnetic resonance renography in adolescents.

PURPOSE: We sought to determine the reproducibility of magnetic resonance imaging renography using 3 different mathematical models and 2 different approaches to convert the relative signal intensity into quantitative indices. Furthermore, we wanted to examine the influence of fluid intake on the obtained renal parameters. MATERIALS AND METHODS: A total of 10 healthy volunteers 13 to 16 years old were subjected to magnetic resonance imaging 3 times within 10 weeks, including an examination where fluid intake was increased. At each examination 0.1 mmol/kg gadolinium diethylenetriamine pentaacetic acid was administrated intravenously as a rapid bolus during a fast magnetic resonance renography sequence. Images were acquired in the coronal plan, and 1,200 images were recorded during approximately 7 minutes. Cortical data were analyzed to estimate absolute and differential function of renal parameters by converting signal intensities into quantitative units. RESULTS: Using the simple approach that a change in magnetic resonance imaging signal is linearly related to the change in gadolinium diethylenetriamine pentaacetic acid concentration, we found reproducibility in the range of 1% to 5% of all estimations of the differential renal function. The relative glomerular ultrafiltration (ml per minute per cm(3) kidney cortex) was calculated and a reproducibility of 7% was observed for relative glomerular ultrafiltration (using the model based on deconvolution). Increased hydration caused a significant change in most parameters. CONCLUSIONS: Contrast enhanced magnetic resonance renography is reproducible in the normal human kidney but excessive water intake has a significant influence on these parameters. Further studies are required to elucidate whether similar measurements can be applied to a kidney with impaired function.

Adolescent↗
PubMed2006

Familial neurohypophyseal diabetes insipidus--an update.

Although molecular research has contributed significantly to our knowledge of familial neurohypophyseal diabetes insipidus (FNDI) for more than a decade, the genetic background and the pathogenesis still is not understood fully. Here we provide a review of the genetic basis of FNDI, present recent progress in the understanding of the molecular mechanisms underlying its development, and survey diagnostic and treatment aspects. FNDI is, in 87 of 89 kindreds known, caused by mutations in the arginine vasopressin (AVP) gene, the pattern of which seems to be largely revealed as only few novel mutations have been identified in recent years. The mutation pattern, together with evidence from clinical, cellular, and animal studies, points toward a pathogenic cascade of events, initiated by protein misfolding, involving intracellular protein accumulation, and ending with degeneration of the AVP producing magnocellular neurons. Molecular research has also provided an important tool in the occasionally difficult differential diagnosis of DI and the opportunity to perform presymptomatic diagnosis. Although FNDI is treated readily with exogenous administration of deamino-D-arginine vasopressin (dDAVP), other treatment options such as gene therapy and enhancement of the endoplasmic reticulum protein quality control could become future treatment modalities.

Animals↗
PubMed2006

Bladder reservoir function in children with monosymptomatic nocturnal enuresis and healthy controls.

PURPOSE: We investigated bladder reservoir function in children with monosymptomatic nocturnal enuresis and in healthy controls. MATERIALS AND METHODS: A total of 18 children with monosymptomatic nocturnal enuresis and 119 controls who were 7 to 13 years old were recruited. Children completed frequency volume charts and measurements of nocturnal urine production. Mean diuresis in the period preceding each voiding was calculated. Those with enuresis were grouped according to bladder capacity and hospitalized for 4 nights, including a baseline night and 3 with an oral water load. Enuresis volumes and post-void residual volume were estimated, allowing the calculation of bladder volume at the time of enuresis. RESULTS: Nine children with monosymptomatic nocturnal enuresis were characterized as having normal bladder capacity and 9 had decreased bladder capacity. We found large intra-individual variability in daytime voided volume in all 3 groups of participants. Children with enuresis and small bladder capacity generally voided with volumes close to maximal voided volume. A total of 93 enuresis episodes were recorded. Large intra-individual variability was seen in bladder volume at enuresis and it was lower than maximal voided volume in more than 50% of episodes. Variability in bladder volume at enuresis was greatest in the patient group with decreased bladder capacity. We found a significant correlation between diuresis and bladder capacity in all groups during the day and night. CONCLUSIONS: There is a great intra-individual diurnal variability in voided volume in children with enuresis and in healthy children. Enuresis seems to occur at bladder volumes that are smaller and larger than the maximal voided volume obtained from voiding charts.

Child↗
PubMed2006

The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children's Continence Society.

PURPOSE: We updated the terminology in the field of pediatric lower urinary tract function. MATERIALS AND METHODS: Discussions were held of the board of the International Children's Continence Society and an extensive reviewing process was done involving all members of the International Children's Continence Society as well as other experts in the field. RESULTS AND CONCLUSIONS: New definitions and a standardized terminology are provided, taking into account changes in the adult sphere and new research results.

Adolescent↗
PubMed2006

Circadian variation of angiotensin II and aldosterone in nocturnal enuresis: relationship to arterial blood pressure and urine output.

PURPOSE: We investigated the circadian rhythm of solute excretion and regulating hormones as well as blood pressure in patients with monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: We included 15 patients with a mean age +/- SE of 13.4 +/- 0.9 years who had monosymptomatic nocturnal enuresis with at least 3 wet nights weekly and a control group of 10 healthy children with a similar age and sex distribution. During inpatient circadian studies urine was collected during 6 periods and blood was drawn at 7 time points during 24 hours. Heart rate and blood pressure was recorded with an ambulatory blood pressure monitor every 30 to 60 minutes. RESULTS: The total patient group excreted a significantly larger nocturnal urine volume than controls (p <0.01). Five patients had marked nocturnal polyuria (nocturnal urine volume greater than the mean in the control group +2 SD), whereas urine output in the remaining patients without polyuria were similar to controls. Nocturnal polyuria was caused mainly by increased nocturnal solute excretion, especially Na. Serum aldosterone and plasma angiotensin II showed a marked circadian rhythm in normal children with a nocturnal increase concomitant with a significant decrease in mean arterial blood pressure during sleep. In contrast, the group of patients with nocturnal polyuria showed a lack of circadian rhythm in all excretion variables as well as an attenuated rhythm in plasma angiotensin II and mean arterial blood pressure. Interestingly this group had normal circadian rhythms of the circadian rhythm markers plasma cortisol and heart rate. CONCLUSIONS: The study suggests that an abnormally large nocturnal excretion of Na caused by selectively attenuated circadian rhythms of Na regulating hormones might be an important pathogenic factor in monosymptomatic nocturnal enuresis.

Adolescent↗
PubMed2006

The role of bladder capacity in antidiuretic and anticholinergic treatment for nocturnal enuresis.

PURPOSE: We evaluated combination treatment with desmopressin and oxybutynin in patients with enuresis who did not respond to desmopressin monotherapy. Furthermore, we compared 2 methods of estimating bladder capacity and evaluated the ability of these methods to predict the response to desmopressin and oxybutynin. MATERIALS AND METHODS: A total of 60 children with a mean age +/- SD of 10.6 +/- 3.0 years who had monosymptomatic nocturnal enuresis completed the study. After a 2-week observation period maximal voided volume during free access to fluid intake was determined by a 2-day frequency-volume chart and maximal voided volume after water load was determined on a separate day. Patients then received 20 mug desmopressin intranasally at bedtime during 2 weeks. In nonresponders to desmopressin with less than a 50% decrease in wet nights 5 mg oxybutynin twice daily was added for another 2 weeks. RESULTS: Of the patients 41 (68%) showed more than 50% decrease in wet nights during the 2-week desmopressin treatment period (4.6 +/- 1.6 to 0.7 +/- 0.8, p <0.001). In desmopressin nonresponders combined treatment with desmopressin and oxybutynin resulted in a further decrease in wet nights (4.0 +/- 1.2 to 1.7 +/- 1.4, p <0.001). Maximal voided volume during free access to fluid intake was significantly higher in desmopressin responders than in nonresponders (244 +/- 111 vs 160 +/- 65 ml, p <0.001). In contrast, maximal voided volume after water load was not significantly different between desmopressin responders and nonresponders. CONCLUSIONS: The study indicates a role for oxybutynin in combination with desmopressin in children who are not responding to desmopressin monotherapy. Maximal voided volume during free access to fluid intake is a clinically useful predictor of the response to desmopressin but not to oxybutynin.

Antidiuretic Agents↗
PubMed2005

Expression of three different mutations in the arginine vasopressin gene suggests genotype-phenotype correlation in familial neurohypophyseal diabetes insipidus kindreds.

OBJECTIVE AND STUDY DESIGN: The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease characterized by a severe and progressive deficiency of AVP secondary to mutations in the gene encoding the AVP precursor. Whereas a number of studies have investigated the pathogenetic mechanisms behind the disease only few studies have included detailed clinical characterization of the affected patients, thereby making genotype-phenotype correlations difficult. The aims of the present study were to investigate the cellular effects of three different adFNDI mutations (A19T, L81P and C110X) by heterologous expression in a neurogenic cell line and to correlate these findings to the corresponding clinical phenotype as determined by extensive clinical tests. RESULTS: The clinical studies showed a later age of onset in the family carrying the A19T mutation (3.4 years, range 2-9 years) compared with families with the L81P and C110X mutations [0.75 year, range 0.5-1 year and 1.0 year (n = 1), respectively]. No other differences could be demonstrated in the clinical phenotype between families. Expression studies showed that each of the three mutant genes caused significant reduction of the amount of immunoreactive AVP in the cell culture medium and severe impairment of the intracellular trafficking and processing of the AVP prohormone, supporting the disease causing nature of all three mutations. However, the A19T mutation was associated with some capacity for processing and trafficking consistent with the clinical observations. Immunoflourescence studies provided evidence of reticular accumulation of protein within the ER in the A19T and C110X mutants but a unique accumulation of much larger aggregates in the L81P, which were localized both within and immediately outside the ER. CONCLUSION: The study suggests a genotype-phenotype correlation with regard to age of onset of diabetes insipidus symptoms and provides support by expression studies.

Adolescent↗
PubMed2004

Six novel mutations in the arginine vasopressin gene in 15 kindreds with autosomal dominant familial neurohypophyseal diabetes insipidus give further insight into the pathogenesis.

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by postnatal arginine vasopressin (AVP) deficiency resulting from mutations in the AVP gene encoding the AVP pre-prohormone. To advance the understanding of adFNDI further, we have searched for mutations in the AVP gene in 15 unrelated kindreds in which diabetes insipidus appeared to be segregating. In nine kindreds, seven different previously described mutations were identified. In each of the other six kindreds, unique novel mutations were identified. Two of these (225A>G and 227G>A) change a nucleotide in the translation initiation codon of the signal peptide, whereas the other four (1797T>C, 1884G>A, 1907T>G, and 2112C>G) predict amino-acid substitutions in the neurophysin II moiety of the AVP prohormone, namely V67A (NP36), G96D (NP65), C104G (NP73), and C116W (NP85). Among these, the mutation predicting the V67A (NP36) substitution is remarkable. It affects a region of the neurophysin II not affected by any other mutations, produces only a minor change, and its inheritance suggests an incomplete penetrance. Our findings both confirm and further extend the mutation pattern that has emerged in adFNDI, suggesting that the mutations affect amino-acid residues known or reasonably presumed to be important for the proper folding and/or dimerization of the neurophysin II moiety of the AVP prohormone.

Arginine Vasopressin↗
PubMed2004

Impaired trafficking of mutated AVP prohormone in cells expressing rare disease genes causing autosomal dominant familial neurohypophyseal diabetes insipidus.

OBJECTIVE AND STUDY DESIGN: Two different mutations in the arginine vasopressin (AVP) gene associated with autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) predict Y21H (AVP2) and V67A (NP36) amino acid substitutions of the AVP prohormone. They are unique in that they change, respectively, the AVP moiety and a region of the neurophysin II domain not so far affected by any mutations. To test whether they affect the cellular handling of the AVP prohormone in a similar manner to previously investigated mutations, they were examined by heterologous expression in cell lines. RESULTS: Both mutations resulted in significantly reduced amounts of immunoreactive AVP in the cell culture medium as determined by radioimmunoassay analysis. Metabolic labelling combined with immunoprecipitation demonstrated that processing and secretion of the mutant prohormones was reduced but not prevented. Finally, confocal laser scanning microscopy showed that normal AVP prohormone and/or its processed products were localized in the tips of the cellular processes, whereas both mutant prohormones were accumulated in the endoplasmic reticulum (ER) and in the case of the V67A prohormone, also in perinuclear structures outside the ER. CONCLUSION: Both mutations result in reduced AVP prohormone processing and secretion probably due to retention in the ER. This supports, at least partly, the hypothesis that the mutations lead to the production of a mutant hormone precursor that fails to fold and/or dimerize properly and, as a consequence, is retained by the ER protein quality control machinery. Perinuclear accumulation of the V67A prohormone outside the ER indicates that additional mechanisms could be involved.

Animals↗
PubMed2004

Differential cellular handling of defective arginine vasopressin (AVP) prohormones in cells expressing mutations of the AVP gene associated with autosomal dominant and recessive familial neurohypophyseal diabetes insipidus.

An unusual mutation in the arginine vasopressin (AVP) gene, predicting a P26L amino acid substitution of the AVP prohormone, is associated with autosomal recessive familial neurohypophyseal diabetes insipidus (FNDI). To investigate whether the cellular handling of the P26L prohormone differed from that of the Y21H prohormone associated with autosomal dominant inheritance of FNDI, the mutations were examined by heterologous expression in cell lines. Immunoprecipitation demonstrated retarded processing and secretion of the Y21H prohormone, whereas the secretion of the P26L prohormone seemed to be unaffected. Confocal laser scanning microscopy showed accumulation of the Y21H prohormone in the endoplasmic reticulum, whereas the P26L prohormone and/or processed products were localized in secretory granules in the cellular processes. RIA analysis showed reduced amounts of immunoreactive Y21H-AVP and P26L-AVP in the cell culture medium. Thus, the recessive mutation does not seem to affect the intracellular trafficking but rather the final processing of the prohormone. Our results provide an important negative control in support of the hypothesis that autosomal dominant inheritance of FNDI is caused by mutations in the AVP gene that alter amino acid residues important for folding and/or dimerization of the neurophysin II moiety of the AVP prohormone and subsequent transport from the endoplasmic reticulum.

Arginine Vasopressin↗
PubMed2003

Autosomal dominant familial neurohypophyseal diabetes insipidus.

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disorder caused by progressive postnatal arginine vasopressin (AVP) deficiency resulting from mutations in the AVP gene encoding the AVP pre-prohormone. It has been suggested that these mutations exert their effect on the cellular handling of the AVP prohormone by leading to the synthesis of mutant hormone precursor that fails to be processed and/or folded properly in the endoplasmic reticulum (ER). As a consequence, it is retained by the ER protein quality control machinery resulting in protein accumulation and initiation of cellular processes leading to degeneration of the AVP producing neuron. This review summarizes the current knowledge on adFNDI and discusses different hypotheses concerning its pathogenesis.

Arginine Vasopressin↗
PubMed2002

Nocturnal enuresis.

PURPOSE OF REVIEW: The purpose of this review is to highlight and comment upon important areas of enuresis research. RECENT FINDINGS: Current areas of pathophysiological focus are nocturnal urine production, in which alternative mechanisms other than deficient vasopressin secretion has been implicated in some patients. Bladder reservoir function has gained renewed interest, and has proved to be one of the best predictors of treatment response to desmopressin. Various aspects of central nervous system function, including arousability and pontine reflexes, are in focus, and molecular genetics has provided firm evidence of a link between enuresis and different chromosomal markers. The therapeutic focus is directed towards a differential approach based upon the underlying mechanism and towards combination therapies such as alarm devices and desmopressin as well as anticholinergic agents and desmopressin. Furthermore, new exciting treatment concepts such as laser acupuncture have shown promising results in initial studies. SUMMARY: Despite recent advances in our understanding of nocturnal enuresis, we are still far from understanding in detail this socially discomfiting and scientifically intriguing condition, and many controversies remain. However, the substantiation that enuresis is a heterogeneous condition that requires a differential approach has provided the basis for further progress.

Arginine Vasopressin↗
PubMed2002

Autosomal dominant neurohypophyseal diabetes insipidus due to substitution of histidine for tyrosine(2) in the vasopressin moiety of the hormone precursor.

The autosomal dominant form of familial neurohypophyseal diabetes insipidus (adFNDI) has been linked to 40 different mutations of the gene encoding the vasopressin-neurophysin II (AVP-NPII) precursor. All of these mutations have been located in either the signal peptide or neurophysin II moiety. We now report a three-generation Turkish kindred in which severe adFNDI cosegregates with a novel missense mutation in the part of the AVP-NPII gene encoding the AVP moiety. This mutation (T-->C at position 285 in the genomic sequence) was found in only one allele and predicts a substitution of histidine for tyrosine at position 2 in AVP. Like other adFNDI mutations, this substitution is expected to impair folding and processing of the precursor, in this case by interfering with normal binding of the AVP and NPII moieties. It is associated clinically with inability to concentrate urine during fluid deprivation, a greater than 80% deficiency of AVP secretion, and absence of the posterior pituitary bright spot on magnetic resonance imaging. These findings are consistent with the hypothesis that mutations in the AVP-NPII gene cause adFNDI by directing the production of a folding incompetent precursor that prevents the expression of the normal allele via a cytotoxic effect on the magnocellular neurons.

Adolescent↗