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Biomedical subjects

Jens C Djurhuus

Publications and source records attributed to Jens C Djurhuus.

13 recordsLinked to original sources

Urinary calcium excretion in healthy children and children with primary monosymptomatic nocturnal enuresis.

PURPOSE: We investigated the role of urinary Ca excretion in monosymptomatic nocturnal enuresis, and defined normality and intra-individual variability in Ca excretion in healthy children. MATERIALS AND METHODS: We included 46 Danish children with desmopressin resistant nocturnal enuresis and 96 healthy controls. We performed fractional urine collections at home during 2 days in controls or during hospitalization in children with enuresis. Urine volume, osmolality, and Ca and creatinine measurements were performed and Ca-to-creatinine ratios were calculated and compared between groups. Based on nocturnal urine output children with enuresis were characterized as having polyuria (nocturnal urine volume greater than 130% of expected bladder capacity) or not having polyuria. RESULTS: We did not find any differences in controls compared with children with enuresis who did not and did have nocturnal polyuria in daytime Ca excretion (mean +/- SE 0.121 +/- 0.012, 0.078 +/- 0.014 and 0.095 +/- 0.020 mg/mg creatinine), nighttime Ca excretion (0.115 +/- 0.011, 0.092 +/- 0.019 and 0.139 +/- 0.029 mg/mg creatinine) or 24-hour Ca excretion (0.118 +/- 0.011, 0.083 +/- 0.014 and 0.106 +/- 0.020 mg/mg creatinine, respectively). Urinary Ca excretion was not influenced by patient age, sex or body weight and, furthermore, we did not find evidence of diurnal variation. However, we observed considerable intra-individual variability in diurnal, nocturnal and total 24-hour urinary Ca-to-creatinine ratios. CONCLUSIONS: These observations contradict several previous reports and speculations on a role of Ca in the pathogenesis of nocturnal enuresis.

Adolescent↗

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↗

Tolterodine treatment for children with symptoms of urinary urge incontinence suggestive of detrusor overactivity: results from 2 randomized, placebo controlled trials.

PURPOSE: We report the results of the first 2 large randomized controlled trials designed to evaluate the efficacy and safety of tolterodine extended release in children 5 to 10 years old with symptoms of urinary urge incontinence suggestive of detrusor overactivity. MATERIALS AND METHODS: Two double-blind, placebo controlled trials were conducted sequentially. Children 5 to 10 years old with incontinence suggestive of detrusor overactivity (1 or more diurnal incontinence episodes per 24 hours) were randomized to tolterodine (2 mg daily) or placebo for 12 weeks. The primary end point was the change from baseline to week 12 in the number of incontinence episodes per week. Changes from baseline in the number of voids per 24 hours and volume of urine per void were also evaluated. Exploratory analyses were conducted to determine whether particular subsets of patients showed differential responses to treatment. RESULTS: A total of 224 and 487 children (mean age 8 years) were randomized to placebo and tolterodine, respectively. Differences in the number of incontinence episodes per week, voids per 24 hours, and volume of urine per void between tolterodine and placebo did not reach statistical significance. This finding may be explained by a high placebo response and under dosage of tolterodine among children with greater body weight. Tolterodine was well tolerated. CONCLUSIONS: Analysis of the primary efficacy outcome did not reveal a statistically significant effect of treatment. However, secondary analyses demonstrated that tolterodine was well tolerated among 5 to 10-year-old children with diurnal incontinence. Exploratory analyses also showed that children weighing 35 kg or less with detrusor overactivity characterized by incontinence and/or frequent voiding benefited most from tolterodine treatment, suggesting that a weight adjusted dosing regimen may be required for optimal response among older and heavier children.

Benzhydryl Compounds↗

The pharmacokinetics of 400 microg of oral desmopressin in elderly patients with nocturia, and the correlation between the absorption of desmopressin and clinical effect.

OBJECTIVE: To investigate the pharmacokinetic profile of oral desmopressin in elderly patients with nocturia, and to analyse any possible correlation between the absorption and clinical effect. PATIENTS AND METHODS: In all, 32 patients were screened to determine the baseline number of nocturnal voids and the nocturia index; of these, 24 fulfilled the inclusion criteria and were enrolled for a pharmacokinetic evaluation of oral desmopressin 400 microg. A double-blind, randomized, placebo-controlled, crossover-effect evaluation period was then used to test the association between the absorption of desmopressin and pharmacodynamic effect. Serial plasma samples were collected for 8 h for a pharmacokinetic analysis of desmopressin. The pharmacodynamics after an equivalent oral dose before bedtime were assessed by measuring changes in the number of nocturnal voids, time to first nocturnal void and nocturnal diuresis, from placebo to active treatment. RESULTS: There was a linear relationship between plasma desmopressin at 2 h after dosing and the area under the plasma concentration curve from 0 to infinity (Pearson's rho 0.923, P < 0.001). Women had a significantly higher plasma desmopressin concentration than men (P = 0.0012) and more adverse events. There was no correlation between plasma desmopressin at 2 h after dosing and the within-patient response in any of the effect variables. Generally, the number of nocturnal voids and nocturnal diuresis were half that with placebo. The time to the first nocturnal void was almost doubled compared with placebo. CONCLUSIONS: There seems to be a relationship between gender, plasma level of desmopressin and the incidence of adverse events. Plasma desmopressin at 2 h after dosing cannot be used to predict the pharmacodynamic response, although desmopressin lowers the nocturnal diuresis and the number of nocturnal voids.

Absorption↗

The circadian rhythm of urine production, and urinary vasopressin and prostaglandin E2 excretion in healthy children.

PURPOSE: In adults and adolescents the transition from day to night is followed by a pronounced decrease in diuresis, as well as reduction in the amount of osmotically active substances excreted. We investigate the circadian variations in urine production in healthy children 3 to 14 years old. MATERIALS AND METHODS: A total of 92 children completed urine collections in 2 consecutive days to be analyzed for electrolytes, urea, creatinine, osmolality, vasopressin and prostaglandin E2. RESULTS: We found a marked reduction in urine output during the night (43.41 +/- 18.53 to 25.69 +/- 12.71 ml per hour) accompanied by a decrease in the amount of electrolytes excreted (sodium 4.44 +/- 2.09 to 2.66 +/- 1.55 mmol per hour and potassium 2.38 +/-0.96 to 0.90 +/- 0.54 mmol per hour). Age and gender did not influence the observed circadian rhythm in the quantity and quality of urine production. Urinary excretion of vasopressin did not seem to reflect the circadian variations previously described for the plasma levels of the hormone. Prostaglandin E2 showed a clear circadian variation with a 30% decrease at night (32.2 +/- 19.0 to 22.0 +/- 12.6 ng/mmol creatinine). CONCLUSIONS: Healthy children exhibit pronounced circadian variations in the amount and composition of urine output with a decrease in nocturnal diuresis and excretion of osmotically active solutes. In the age range of 3 to 14 years neither age nor gender seems to affect this rhythm. Vasopressin-to-prostaglandin E2 excretion ratio appears to be of importance for regulation of urine production.

Adolescent↗

The outcome of detrusor myotomy in children with neurogenic bladder dysfunction.

PURPOSE: We evaluate the outcome of detrusor myotomy for neurogenic bladder dysfunction (NBD) in children. MATERIALS AND METHODS: A retrospective analysis was performed of data compiled from medical and urodynamic records of children younger than 16 years with NBD who had undergone detrusor myotomy from 1992 to 2000 at our department. RESULTS: Surgery was performed in 14 children with a mean age +/- SD of 6.7 +/- 4.3 years (range 0.9 to 14.2) and mean followup of 5.9 +/- 1.7 years. All patients were diagnosed with NBD, which was the result of myelomeningocele in 9, sacral agenesis in 2, lumbosacral lipoma in 1, multiple vertebral anomalies in 1 and spinal neuroblastoma in 1. Main indications for surgery included urinary incontinence in 11 cases and high pressure/low capacity bladders with vesicoureteral reflux and impending renal damage in 8. No major postoperative complications were recorded. Although mean maximal cystometric bladder capacity was unchanged 1 month postoperatively (89.7 +/- 70.6 ml) compared to preoperatively (92.5 +/- 75.1 ml, p = 0.87), significant increments of 216%, 237% and 292% were measurable at 3 months, 1 year and 5 years, respectively. Ultimately most of the patients approached age specific capacities. Complete continence on clean intermittent catheterization was achieved by 8 of 11 patients and improved markedly in 1. Reflux was alleviated in 6 cases and improved in 1. Kidney function developed normally in all but 1 patient with persistent reflux. CONCLUSIONS: When feasible, detrusor myotomy offers a safe and effective alternative for the management of pharmacologically intractable NBD in children.

Adolescent↗

Resistive index: an experimental study of acute complete unilateral ureteral obstruction.

RATIONALE AND OBJECTIVES: To study the effects of acute complete unilateral ureteral obstruction (UUO) and release on porcine renal resistive index (RI). METHODS: Under general anesthesia, UUO was induced in six pigs. RI was measured bilaterally at predetermined intervals for 4 hours of UUO and 1 hour of release. Additionally, measures of renal blood flow (RBF), glomerular filtration rate (GFR), arterial blood pressure, renal vascular resistance (RVR), and ipsilateral renal intrapelvic pressure (IPP) were obtained. RESULTS: UUO and resultant progressive IPP increase caused prompt and significant ipsilateral RI elevation, and contralateral RI decrease. Concomitantly, ipsilateral RVR increased significantly while RBF and GFR declined, both significantly. Release of obstruction saw an almost immediate normalization of ipsilateral RI, RVR and RBF while ipsilateral GFR assumed 80% of baseline value 15 minutes postobstruction. Throughout the experiment, ipsilateral RI correlated significantly with changes in IPP, GFR, RBF, and RVR with correlation coefficients of 0.844, -0.851, -0.898, and 0.836 respectively ( < 0.001). CONCLUSIONS: UUO causes a divergent RI response that is instantly reversed upon release. IPP seems to be the principal effector of these changes in the early phases of UUO.

Acute Disease↗

Losartan attenuates renal vasoconstriction in response to acute unilateral ureteral occlusion in pigs.

Unilateral ureteral obstruction in pigs is associated with an enhanced, de novo generation of angiotensin II from the ipsilateral kidney. In order to further investigate the role of this system during unilateral ureter obstruction, the renal hemodynamic response to the non-peptide angiotensin II antagonist losartan was investigated. Danish land race pigs were operated on under general anesthesia. Catheters were placed in both renal veins by x-ray and ultrasonic flow probes were mounted on the renal arteries. Losartan (2 mg/kg/h) was administered intravenously to an experimental group ( n=9) continuously over 8 h of unilateral ureteral occlusion. This group was then compared to a matched control group which received only saline ( n=6). Ipsilateral pelvic pressure, renal blood flow using ultrasound transit time, glomerular filtration rate, mean arterial pressure and heart rate were measured. Renal handling of angiotensin II was examined by determining the renal extraction and secretion rates of immunoreactive angiotensin II. The anticipated reduction in ipsilateral renal blood flow after the onset of obstruction was attenuated in the losartan treated pigs, but the ipsilateral glomerular filtration rate was unaffected as compared with the controls. In the losartan group, the increase in renal vascular resistance was significantly reduced compared with un-treated controls (141+/-25% vs 217+/-24%, P<0.05). Plasma immunoreactive angiotensin II increased significantly from all three sample locations in both groups after the onset of obstruction, being more pronounced in the losartan treated group in which immunoreactive angiotensin II from the ipsilateral renal vein increased from 5.1+/-0.5 pmol/l to 41.6+/-19.6 pmol/l, P=0.027. In the controls immunoreactive angiotensin II increased from 2.7+/-0.3 pmol/l to 24.8+/-10.2 pmol/l. Furthermore, plasma aldosterone was significantly reduced after losartan administration (from 80.4 pmol/l to 36.0 pmol/l, P=0.005), indicating effective blockade of the angiotensin II type-1 receptor. The results from the present study suggest that continuous intravenous administration of losartan blocks the angiotensin II receptor mediated effects in the pig. Losartan is able to reduce ipsilateral vasoconstriction in the obstructed kidney during unilateral ureter obstruction supporting the view that angiotensin II is an important mediator of vasoconstriction during unilateral ureter obstruction in the pig model with acute unilateral occlusion of the ureter.

Acute Disease↗

Urodynamic patterns of normal male micturition: influence of water consumption on urine production and detrusor function.

PURPOSE: Urodynamic characterization of normal male micturition can be a useful standard in the analysis of data on patients complaining of voiding dysfunction. The validity of such a standard is based on the need to obtain baseline parameters of pressure flow values, an important consideration when evaluating prostatic obstruction and its treatment. While current numerical pressure flow values provide a useful summary of the voiding sequence, a more complete analysis of the pattern of normal voiding may reveal more functionally useful information concerning micturition. We establish basic experimental conditions that simulate normal voiding of physiologically produced urine by the kidneys measured at intervals representing real stages of bladder filling. We report the results of an investigation designed to study consecutive micturitions at bladder volumes determined by water consumption and endogenous circadian rhythm. Our particular focus is to examine critically the urodynamic pattern of pressure flow and obtain evidence to support the hypothesis that fluid consumption has an important role in detrusor function. MATERIALS AND METHODS: Urodynamic studies were conducted on 39 asymptomatic male volunteers with a mean age of 25.8 years (range 21 to 31) and mean weight of 75.5 kg. (range 63 to 95). Volunteers were divided into 2 groups according to water consumption regimen of 30 ml./kg. daily (17 patients, group 1) and 60 ml./kg. daily (12, group 2). Bladder pressure was monitored via a suprapubic catheter and abdominal pressure was measured via a rectal balloon using an ambulatory system. Average duration of each monitoring period was 20.5 hours. Detrusor pressure and flow rate records from each subject were identified, and consecutive filling and voiding phases were averaged during the entire monitoring period using the onset of micturition as a time marker. The average pattern of pressure, flow rate, cumulative volume and contractility curves for each subject, as well each for group, was computed and graphically presented. For each group the average parameters of urethral opening pressure, maximum detrusor pressure, detrusor pressure at maximum flow rate, bladder capacity and bladder contraction strength were calculated and compared statistically. Numerical values are mean +/- SE. RESULTS: Water consumption and urine production rate influenced the pattern and many of the urodynamic parameters of micturition. In both groups there was a detrusor pressure increase before voiding and numerically maximum detrusor pressure consistently occurred before micturition started. Micturition pattern showed an asymptotic relationship between pressure and flow. Doubling of water consumption increased urethral opening pressure from 51.2 +/- 3.2 to 61.5 +/- 5.1 (p <0.05), maximum detrusor pressure from 58.9 +/- 4.5 to 70.0 +/- 6.2 cm. H(2)O (p <0.01) and contractility from 15.4 +/- 1.4 to 17.7 +/- 1.4 w/m(2). There were no significant differences due to water consumption in maximum flow rate (24.4 +/- 1.4 to 25.2 +/- 1.8 ml. per second) or bladder capacity (286 +/- 20 to 329 +/- 15 ml.) but a significant increase in the number of micturitions from 5.8 +/- 0.5 to 9.8 +/- 0.5 per day (p <0.001) proportional to water consumption. CONCLUSIONS: The configuration of the observed pressure flow characteristics of the normal male is suggestive of the "Starlings law" relationship and the pattern of the urodynamic parameters were markedly different from those reported in the current standardization literature, suggesting the need to revise the current concept of normal male micturition. Voiding pressure and contractility increased in accordance with water consumption and urine production.

Adult↗

Female nocturia.

Many elderly experience nocturia to such a degree that it influences their quality of life. Different studies use equivocal definitions when trying to analyze data on nocturia. The literature on etiology of female nocturia is sparse, whereas male nocturia has been studied rather extensively because of the association with lower urinary tract symptoms (LUTS). At present the few studies on female nocturia questions the fact that male and female nocturia have identical etiologies. This review will go through the present reports on prevalence and etiology of nocturia among women with reference to the male situation.

Adult↗

Demographics of enuresis patients attending a referral centre.

OBJECTIVE: To study and compare the demography of enuretic children 7-16 years old attending a tertiary referral centre for childhood urinary incontinence, with that of normal children and what is generally known about enuretics from population-based studies. METHODS AND MATERIALS: This was a retrospective analysis of data compiled from 298 enuretic patients referred to The Centre of Child Incontinence, Aarhus University Hospital, Skejby, Denmark, and 53 healthy controls. Data was obtained by conducting standardised questionnaire interviews. Patients were stratified according to accompanying symptoms and severity of enuresis. Statistical analysis of the results was then performed. RESULTS: Two hundred and ninety-three patients had sufficient data registered to allow reliable analysis. Male-female ratio was 2.2:1. Primary and secondary enuresis was found in 87.4% and 11.6% of the patients respectively. Enuresis was associated with a reported history of bronchial asthma (p < 0.05), verified allergy (p < 0.05) and a positive family history of the same disorder (p < 0.01). No association with psycho-developmental factors was evident. Approximately 98% of the patients had undergone some form of therapy at presentation. 74.1% of the patients had pure monosymptomatic enuresis, 16.4% had day and night time incontinence, while the remaining 9.6% had nocturnal incontinence combined with other lower urinary tract symptoms other than daytime wetting. CONCLUSIONS: The demography of our patient population was, with a few exceptions, within the confines of what has previously been reported. Our results also reaffirmed the heterogeneity of enuretic patients.

Adolescent↗

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↗