The effect of puberty on diurnal sodium regulation.

The aim of this study was to investigate the impact of sex and puberty stage on circadian changes in sodium excretion, sodium-regulating hormones, and hemodynamics. Thirty-nine healthy volunteers (9 prepuberty boys, 10 prepuberty girls, 10 puberty boys, and 10 puberty girls) were included. They all underwent a 24-h circadian in-patient study under standardized conditions regarding activity, diet, and fluid intake. Blood samples were drawn every 4 h, and the urine was collected in fractions. Blood pressure and heart rate were noninvasively monitored. Atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin were measured in blood. Children in puberty had lower plasma levels of renin (P<0.05) and angiotensin II (P<0.05) and a 26% reduction in filtered sodium without changes in sodium excretion compared with prepuberty children. A circadian rhythm in sodium excretion, the renin-angiotensin system, ANP, and blood pressure was found with a midnight ANP peak (P<0.001), a nighttime decrease in hemodynamic parameters (P<0.001), an increase in plasma renin (P<0.001) and angiotensin II (P<0.001), and a decrease in sodium excretion (P<0.001) mainly on the basis of increased sodium reabsorption (P<0.001). The timing of the changes did not depend on sex or puberty group. There is a circadian rhythm of sodium excretion and sodium regulation in 7- to 15-yr-old children. This rhythm is similar in boys and girls. As an important new finding, puberty changes the plasma levels of renin and angiotensin II without changing the amount of sodium excreted or the day to night sodium excretion ratio.

Puberty alters renal water handling.

We investigated the influence of sex and puberty stage on circadian urine production and levels of antidiuretic hormone [arginine vasopressin (AVP)] in healthy children. Thirty-nine volunteers (9 prepuberty boys, 10 prepuberty girls, 10 midpuberty boys, and 10 midpuberty girls) were included. All participants underwent a 24-h circadian inpatient study under standardized conditions regarding Na(+) and fluid intake. Blood samples were drawn every 4 h for measurements of plasma AVP, serum 17-ß-estradiol, and testosterone, and urine was fractionally collected for measurements of electrolytes, aquaporin (AQP)2, and PGE2. We found a marked nighttime decrease in diuresis (from 1.69 ± 0.08 to 0.86 ± 0.06 ml·kg(-1)·h(-1), P < 0.001) caused by a significant nighttime increase in solute-free water reabsorption (TcH2O; day-to-night ratio: 0.64 ± 0.07, P < 0.001) concurrent with a significant decrease in osmotic excretion (day-to-night ratio: 1.23 ± 0.06, P < 0.001). Plasma AVP expressed a circadian rhythm (P < 0.01) with a nighttime increase and peak levels at midnight (0.49 ± 0.05 pg/ml). The circadian plasma AVP rhythm was not influenced by sex (P = 0.56) or puberty stage (P = 0.73). There was significantly higher nighttime TcH2O in prepuberty children. This concurred with increased nighttime urinary AQP2 excretion in prepuberty children. Urinary PGE2 exhibited a circadian rhythm independent of sex or puberty stage. Levels of serum 17ß-estradiol and testosterone were as expected for sex and puberty stage, and no effect on the AVP-AQP2-TcH2O axis was observed. This study found a circadian rhythm of plasma AVP independent of sex and puberty stage, although nighttime TcH2O was higher and AQP2 excretion was more pronounced in prepuberty children, suggesting higher prepuberty renal AVP sensitivity.

Sleep deprivation induces excess diuresis and natriuresis in healthy children.

Urine production is reduced at night, allowing undisturbed sleep. This study was undertaken to show the effect of sleep deprivation (SD) on urine production in healthy children. Special focus was on gender and children at an age where enuresis is still prominent. Twenty healthy children (10 girls) underwent two 24-h studies, randomly assigned to either sleep or SD on the first study night. Diet and fluid intake were standardized. Blood samples were drawn every 4 h during daytime and every 2 h at night. Urine was fractionally collected. Blood pressure and heart rate were noninvasively monitored. Blood was analyzed for plasma antidiuretic hormone (AVP), atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and renin. Urine was analyzed for aquaporin-2 and PGE(2). Successful SD was achieved in all participants with a minimum of 4 h 50 min, and full-night SD was obtained in 50% of the participants. During SD, both boys and girls produced markedly larger amounts of urine than during normal sleep (477 ± 145 vs. 291 ± 86 ml, P < 0.01). SD increased urinary excretion of sodium (0.17 ± 0.05 vs. 0.10 ± 0.03 mmol·kg(-1)·h(-1)) whereas solute-free water reabsorption remained unchanged. SD induced a significant fall in nighttime plasma AVP (P < 0.01), renin (P < 0.05), angiotensin II (P < 0.001), and aldosterone (P < 0.05) whereas plasma ANP levels remained uninfluenced (P = 0.807). Nighttime blood pressure and heart rate were significantly higher during SD (mean arterial pressure: 78.5 ± 8.0 vs. 74.7 ± 8.7 mmHg, P < 0.001). SD leads to natriuresis and excess diuresis in healthy children. The underlying mechanism could be a reduced nighttime dip in blood pressure and a decrease in renin-angiotensin-aldosterone system levels during sleep deprivation.

Age related nocturnal urine volume and maximum voided volume in healthy children: reappraisal of International Children's Continence Society definitions.

PURPOSE: We determined normal, age related reference data regarding maximum voided volume and nocturnal urine production using the same methodology as in clinical practice. MATERIALS AND METHODS: A total of 62 girls and 86 boys without enuresis (mean +/- SD age 9.64 +/- 2.63 years, range 3 to 15) completed 4 days (2 weekends) of frequency-volume charts and 14 days of home recording of nocturnal urine production. From these recordings maximum voided volume with and without first morning void was derived for each subject. Also, average nocturnal urine volume with and without nocturia was calculated. Percentiles were produced by dividing the population into 1-year age groups. RESULTS: Based on 2,836 daytime voids and 1,977 overnight recordings, maximum voided volume and nocturnal urine volume showed a significant linear relationship with age but not with gender. Maximum voided volume with first morning void was significantly higher than without (403 +/- 137 ml vs 281 +/- 112 ml, p <0.0001) and the 50th percentile line of maximum voided volume with first morning void was 80 to 100 ml higher than Koff's formula (30 x [age + 1] ml). Conversely the 50th percentile of maximum voided volume without first morning void was almost identical to Koff's formula. Regarding nocturnal measurements, nocturia was noted on 128 nights (6.5%) and nocturnal urine volume on nights with nocturia was significantly higher than on nights without nocturia (365 +/- 160 ml vs 248 +/- 75 ml, respectively, p <0.0001). The 97.5th nocturnal urine volume percentile line of healthy children deviated markedly from the current International Children's Continence Society definition of nocturnal polyuria, especially at low and high ages. CONCLUSIONS: We demonstrate clearly that the universally used formula 30 x (age + 1) ml is indeed valid for a population of healthy Danish children but only if the first morning void is disregarded. Furthermore, we question the validity of the current International Children's Continence Society formula for nocturnal polyuria (nocturnal urine volume greater than 130% of maximum voided volume for age), and instead we propose the formula, nocturnal urine volume greater than 20 x (age + 9) ml.

Pyelonephritis in persons after age 50 as a clinical marker of urogenital cancer.

OBJECTIVES: Urinary tract infections have been linked with urinary tract cancer, but the association remains controversial. We examined whether pyelonephritis is a clinical marker of urogenital cancer. METHODS: We used Danish medical databases to create a population-based cohort of patients with an incident hospital-based pyelonephritis diagnosis during 1994-2013. Follow-up for cancer began at pyelonephritis diagnosis and ended on 30 November 2013. We restricted the cohort to patients older than 50 years, as urogenital cancer risk in the younger population is low. We calculated the absolute risk of urogenital cancer and the standardized incidence ratio (SIR) comparing risk observed in pyelonephritis patients to risk expected in the general population of Denmark. RESULTS: Among 15 070 patients with pyelonephritis, we observed 197 urinary tract cancers and 374 genital organ cancers over a 20-year follow-up period. The absolute risk of urogenital cancer was 1.5% 6 months after a pyelonephritis diagnosis, and the cumulative risk was 3.0% at 5 years. During the first 6 months following a pyelonephritis diagnosis, the SIR of urogenital cancer was 8.56 (95% CI 7.49-9.75). Between 6 and 12 months following this diagnosis, the SIR was 1.75 (95% CI 1.26-2.35), and beyond 1 year the SIR was approximately unity for most cancers. Notably, the SIR for bladder cancer among women remained elevated beyond 1 year of follow-up. CONCLUSIONS: Patients presenting with a hospital-based diagnosis of pyelonephritis had a higher 6-month risk of urogenital cancer than expected. However, causation cannot be inferred because of the study design.

Evaluation of complete and partially obstructed kidneys using Gd-DTPA enhanced dynamic MRI in adolescent swine.

PURPOSE: Aim of this study was to evaluate the dynamic changes in renal relative signal intensity (RSI) following the administration of Gd-DTPA in adolescent pigs with complete and partial unilateral ureteric obstruction. METHODS: Pigs were divided into 3 groups: partial and complete unilateral ureteric obstruction and controls. Complete unilateral ureteric obstruction (CUUO) was created by ligating the left ureter, whereas partial unilateral ureteric obstruction (PUUO) was created in pigs of 2 weeks of age by embedding the left ureter into the psoas muscle. Dynamic MRI was performed before and at 0 - 60 min after an intravenous bolus injection of Gd-DTPA. Mean RSI of the renal cortex, medulla and pelvis was measured and interpreted as an indirect measure of the renal function. In addition, renography was performed, and renal morphology was examined IN VITRO. RESULTS: Three phases of RSI were identified. The dynamic RSI patterns differed markedly between obstructed and control kidneys. In PUUO kidneys, Phase 1 of the mean RSI of the cortex and medulla demonstrated a decreased amplitude and prolonged duration, whereas in Phase 2 the mean RSI of the pelvis was increased. In acute CUUO kidneys, the mean RSI patterns were similar to those of controls, except for a significant increase of the pelvic mean RSI. CONCLUSIONS: Gd-DTPA enhanced dynamic MRI allowed a characterization and differentiation of renal function and morphology of normal and obstructed kidneys, and secondly, provided potentially important information on renal concentrative and filtration availability.

Aquaporin expression in the fetal porcine urinary tract changes during gestation.

The expression of aquaporins (AQPs) in the fetal porcine urinary tract and its relation to gestational age has not been established. Tissue samples from the renal pelvis, ureter, bladder and urethra were obtained from porcine fetuses. Samples were examined by RT-PCR (AQPs 1-11), QPCR (AQPs positive on RT-PCR), and immunohistochemistry. Bladder samples were additionally examined by Western blotting. RNA was extracted from 76 tissue samples obtained from 19 fetuses. Gestational age was 60 (n=11) or 100 days (n=8). PCR showed that AQP1, 3, 9 and 11 mRNA was expressed in all locations. The expression of AQP3 increased significantly at all four locations with gestational age, whereas AQP11 significantly decreased. AQP1 expression increased in the ureter, bladder and urethra. AQP9 mRNA expression increased in the urethra and bladder, but decreased in the ureter. AQP5 was expressed only in the urethra. Immunohistochemistry showed AQP1 staining in sub-urothelial vessels at all locations. Western blotting analysis confirmed increased AQP1 protein levels in bladder samples during gestation. Expression levels of AQP1, 3, 5, 9 and 11 in the urinary tract change during gestation, and further studies are needed to provide insights into normal and pathophysiological water handling mechanisms in the fetus.

Ano-rectal motility responses to pelvic, hypogastric and pudendal nerve stimulation in the Göttingen minipig.

UNLABELLED: We investigated the effect of efferent stimulation of the pelvic (PN), hypogastric (HGN) and pudendal (PuN) nerves on ano-rectal motility in Göttingen minipigs using an impedance planimetry probe. Changes in the rectal cross-sectional area (CSA) at five axial positions and pressures in the rectum and anal canal were investigated simultaneously. Pelvic nerve stimulation elicited a CSA decrease in the proximal part of the rectum and a simultaneous CSA increase in its distal part. Anal pressure also decreased. Hypogastric nerve and PuN stimulation elicited an increase in anal pressure, but no rectal response. Severing the HGN produced a persistent reduction in resting anal pressure, but no change was observed when the PN and the PuN were severed. Stimulation of the distal part of all three nerves produced a persistent response. Administration of phentolamine and pancouronium eliminated the response to stimulation of the HGN and the PuN, respectively. CONCLUSION: Rectal responses to PN stimulation vary more than previously suggested. The HGN has an excitatory effect on the internal anal sphincter, and the PuN on the external anal sphincter. However, the PuN plays no major role in maintaining basal anal pressure.

What is a representative voiding pattern in children with lower urinary tract symptoms? Lack of consistent findings in ambulatory and conventional urodynamic tests.

BACKGROUND: Conventional urodynamics (CU) is a highly standardized evaluation of lower urinary tract function. However, in pediatric patients there is concern that the reliability of measurements could be influenced by development effects and measurement variability, as well as by the unfamiliar clinical environment. Ambulatory urodynamics (AU) provides an alternative to this - it uses natural filling, is measured over a prolonged period, and is conducted in a child-friendly environment. OBJECTIVE: The aim of this study was to conduct a comparative analysis of AU and CU to evaluate the consistency in voiding patterns obtained with these two methods of urodynamic testing. STUDY DESIGN: Urodynamic parameters obtained by AU and CU methods in 50 pediatric patients aged >5 years were retrospectively analyzed. Voiding patterns were categorized into six types: coordinated contraction, detrusor after-contraction, fluctuated contraction, pre-void contraction, relief voiding, and weak or absent contraction. Voiding patterns were used to determine the repeatability within urodynamic tests and to identify consistency between AU and CU tests. Five urodynamic parameters were quantified and compared between AU and CU: voided volume, flow rate, maximum detrusor pressure, and detrusor pressure at peak flow rate. For inter-observer variation analysis, 100 voiding curves were randomly selected and categorized by two independent observers; inter-observer agreement was evaluated using the kappa statistic. RESULTS: A single pattern of voiding was identified in five patients using AU and 37 using CU. Consistency of a single pattern between AU and CU was identified in three patients, and consistency between a predominant pattern with AU, defined by one type of voiding occurring >50% of one's voids, and a single pattern with CU was identified in 10 patients (summary table). Flow rates were similar between methods; however, higher maximum detrusor pressure and detrusor pressure at peak flow and lower voided volume were recorded with AU. DISCUSSION: AU resulted in more diverse voiding patterns. Along with the differences in measured urodynamic parameters challenges the application of findings from one method to form a clinical diagnosis. Furthermore, CU may not be as sensitive as AU to the variability in lower urinary tract pathophysiology. CONCLUSIONS: More diverse voiding patterns were identified in AU compared with CU, with a lack of consistency in identified voiding pattern in both methods. Therefore, the urodynamic findings in children may have to be analyzed in more detail, taking the variations into account.

Effects of rapamycin on renal hemodynamics, water and sodium excretion, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide, and vasopressin in pigs.

We have investigated the acute effects of rapamycin on renal hemodynamics, water, sodium and lithium excretion rates, and plasma levels of angiotensin II, aldosterone, atrial natriuretic peptide and vasopressin in 34 Lancaster/Yorkshire female pigs, a breed that has a renal structure/function resembling that of the human kidney. Three different dosages were given over a 1-hr period: dose A, 0.1 mg/kg (n = 8); dose B, 0.2 mg/kg (n = 8); dose C, 0.4 mg/kg (n = 8); and P, placebo vehicle (n = 10). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by constant infusion clearance technique using 125I-iothalamate and 131I-hippuran, and hormonal parameters were measured by RIA. Renal hemodynamics, water and sodium excretion rates, and tubular function, evaluated by the lithium clearance technique, were unchanged both during and up to 2 hr after rapamycin infusion, although GFR and RPF increased when rapamycin was given in supratherapeutic dosages of 0.4 mg/kg (GFR: P, 4.4%; A, 7.9%; B, 2.5%; C, 13.3% [P < 0.05]; RPF: P, 7.1%; A, 4.9%; B, 3.9%; C, 15.3% [P < 0.01], median values). It is concluded that infusion of rapamycin has no acute deleterious effects on renal function in pigs in therapeutic to supratherapeutic dosages.

Enuresis as protective factor in vesicoureteral reflux.

In 83 patients with non-neurologic, nonoperated vesicoureteral reflux the relation between enuresis and nephropathy was analyzed. The material showed that in spite of identical age, sex distribution, previous history of recurrent urinary tract infections, and the number of refluxing units, patients with enuresis showed a significantly lower degree of reflux nephropathy. This significant difference was even more pronounced when the age of the patients was considered. Thus patients below the age of ten showed reflux nephropathy in 25 per cent of the refluxing units in enuretic patients compared with 30.8 per cent in the nonenuretic patients. Above the age of ten 76.2 per cent of the refluxing units showed renal scarring in the nonenuretics compared with 27.8 per cent in the enuretics. The study stresses the importance of lower urinary tract malfunction in the pathogenesis of reflux. Enuresis might act as a safety valve mechanism reducing the possibility of reflux nephropathy.

Effects of vasoactive intestinal peptide, peptide histidine methionine, and neuropeptide Y on intracavernous pressure in the rabbit.

In anesthesized white rabbits blood was extracorporeally circulated from the left carotid artery into the penile corporeal bodies with a constant flow rate. Corpus cavernosum pressure (CCP) responses to intracavernous injections of drugs were recorded in animals with aortic nonocclusion and aortic occlusion, respectively. Vasoactive intestinal polypeptide (VIP, 1 microgram, 5 micrograms, and 20 micrograms), dissolved in 0.5 mL volumes, induced no significant increases in CCP compared with equivalent volumes of solvent, but the peptide increased the time interval until return of CCP to steady state level. Peptide histidine methionine induced a significant increase in the maximal CCP obtained in nonocclusion, and the time interval until return of CCP to steady state levels was increased in both aortic nonocclusion and occlusion. Neuropeptide Y produced an increase in the maximal CCP in animals with aortic occlusion, and a minor increase in the time interval until return of CCP values to steady state levels in both aortic nonocclusion and occlusion. Thus, all the peptides tested were capable of influencing the smooth muscle tissues involved in penile outflow regulation.

Experimental evaluation of furosemide renography in unobstructed and partially obstructed upper urinary tracts in pigs.

To evaluate the reliability and the constancy of the furosemide renography an experimental evaluation of the test has been performed. A standardized unilateral partial proximal ureteral obstruction was applied to 11 pigs. Preoperatively and again weekly in the three weeks following obstruction a furosemide renogram (FR) was done. The furosemide renography was a very constant parameter in the unobstructed kidney (85%) and in the partly obstructed kidney (85%). A type I FR pattern (O'Reilly classification) was an exact indicator of an unobstructed pelvis. After partial ureteral obstruction, an immediate change in the FR pattern was seen either into type II or type IIIa renography. In this experimental study furosemide renography was found to be a reliable tool in the differentiation between the unobstructed normal renal pelves and the partly obstructed dilated renal pelves.

Constant perfusion provocation in idiopathic hydronephrosis.

Twenty-two hydronephrotic units in 20 patients underwent preoperative pressure flow study in combination with electromyographic study of pelvic and ureteric peristalsis. Ten units had a continuous pressure rise during perfusion, whereas the rest had a stabilization of the intrapelvic pressure below 20 cm. of water. The high pressure group was identical with the low pressure group concerning degree of hydronephrosis judged by intravenous urography and function judged by the two-minute uptake of isotope on the renogram. The major difference was the presence of aberrant vessels which were present in 7 of 10 high pressure units and absent in 8 of 12 low pressure units. Long-term records prior to surgery were obtainable in only 1 patient who had spontaneous progression of hydronephrosis during a ten-year period. This unit had a low pressure response to perfusion. The investigation seems to indicate that pressure flow studies might reveal external obstruction, an obstruction which might not be fundamental to the course of the disease. More studies are needed before consequence are to be taken from urodynamic studies of the upper urinary tract.

Simultaneous registration of sleep-stages and bladder activity in enuresis.

A combined monitoring of sleep stages and bladder activity for the evaluation of enuresis is on trial. Polygraphic recordings in 7 patients, comprising the preliminary material, have shown single-event bladder contractions without forewarning or changes in sleep stages. A volume dependency of the enuresis episodes seems so far to be a major mechanism.

New probe for the measurement of dynamic changes in the rectum.

Conventional mano-volumetric techniques cannot measure changes in circumferential dimensions at several axial positions within a bowel segment. Our aims were to validate a new impedance planimetry probe for simultaneously measuring the cross-sectional area (CSA) at five axial positions in vitro and in vivo in 10 anesthetized pigs. The day-to-day coefficient of variation (CV) for CSA measured by the probe in cylindrical tubes of known diameter was 0.8-9.5%. The mean from actual diameter deviation ranged from 2.3 to 6.7%. In a conical tube the day-to-day CV was 2.3-8% and mean percentage deviation -2.8 to 1.0. Interposed narrowing sections caused a total CV of 7-13%. In vivo studies revealed variations in CSA, associated with expulsion of flatus. It is concluded that impedance planimetry allows simultaneous measurement of CSA at several levels within the rectum. In vitro validity was acceptable and alterations in lumen diameter were identified in vivo.

Dynamics of the upper urinary tract: II. The effect of variations of peristaltic frequency and bladder pressure on pyeloureteral pressure/flow relations.

The dynamics of pyeloureteral flow is described when there is no peristalsis and for peristalsis of high and intermediate frequencies, on the assumption that the ureter is uniform except in the mid-ureter and at the outlet. The possibility of upstream transmission of bladder pressure variations to the renal pelvis is considered. The overall behaviour depends on three principal variables, the maximum tube pressure in the contraction waves, the intrinsic peristaltic carrying capacity and the peristaltic frequency f, expressed in the form fT where T is the time for a peristaltic contraction wave to sweep through the ureter. At intermediate peristaltic frequencies (fT less than but comparable with one) oscillatory flow patterns can occur, in which periods of peristaltically driven flow alternate with extraperistaltic periods of flow through the open ureter. The kidney is better isolated from bladder pressure variations when the peristaltic frequency is high, but high peristaltic frequency can by itself lead to elevated renal pelvic pressure if the flow rate is high. Experimental observations in pigs are presented to support these conclusions.

In vivo measurement of T1 and T2 relaxivity in the kidney cortex of the pig--based on a two-compartment steady-state model.

A two-compartment system for approximating five successive steady-state levels of gadopentetate dimeglumine (Gd-DTPA) concentration in pigs was developed. The method of calculating Gd-DTPA concentration was based on a simultaneous reference determination of 99mTc-DTPA. Experimental and theoretical results showed a steady state after 25 min. The nuclear magnetic resonance (NMR) relaxivities of Gd-DTPA were determined in vivo in pig kidneys during steady-state levels. T1 relaxivity (R1) and T2 relaxivity (R2) in the kidney cortex were found to be 1.1+/-0.03 and 2.0+/-0.2 (s(-1) mM(-1)), respectively. R1 and R2, in in vitro human plasma solutions at 25 degrees C were 5.3+/-0.02 and 5.8+/-0.06 s-1 mM-1 and at 37 degrees C 4.3+/-0.04 and 4.9+/-0.01 s(-1) mM(-1). Thus, the in vivo relaxivities were reduced 3.9 and 2.5 times for R1 and R2, respectively, compared to the in vitro relaxivities. This marked difference in relaxivities between tissue and plasma may be the result of the difference in steric relations. In plasma, the mobility and distribution of the Gd-DTPA complex are unrestricted, whereas they may be reduced in the tissues because of the close proximity to the cell wall, to the proteins and to other extracellular elements and compartments.

Quantitative assessment of Gd-DTPA contrast agent from signal enhancement: an in-vitro study.

Quantitative determination of in-vivo gadolinium diethylenetriamine-pentaacid (Gd-DTPA) concentration is attractive in various studies involving perfusion, tracer kinetics and permeability constants. Using a 1.5 T clinical system and a 7 T small-bore system, we evaluated a method for absolute determination of Gd-DTPA concentrations in plasma solutions. Different solutions of Gd-DTPA and (99m)Tc-DTPA were mixed in human plasma and concentrations in the range of 0-5.0 mmol/l (1.5 T system) or 0-3.0 mmol/l (7 T system) of Gd-DTPA were divided into thirteen tubes. All MRI measurements were carried out using conventional sequences (SE, FLASH and GRASS). The MR measured intensity was converted to Gd-DTPA concentration by mathematical interpretation of the sequences. All MRI sequences showed, that the measured concentrations of Gd-DTPA revealed a slight non-linear difference compared with the calculated Gd-DTPA concentrations determined by the plasma (99m)Tc-DTPA using gamma counting. This non-linearity was most pronounced at high Gd-DTPA concentrations, suggesting that the discrepancy could be a result of an increased plasma relaxivity at higher concentrations. Adjustment of measured Gd-DTPA concentration was therefore performed using a selected power function, A[Gd-DTPA](a), which yielded the best linear relationship. Regression analysis showed that the scaling constant (A) varied from 0.11 to 97.45 and the power constant (a) varied from 0.83 to 1.6. Based on these constants, the MRI measured concentrations of Gd-DTPA did not differ from the calculated concentrations of Gd-DTPA obtained from reference measurements of (99m)Tc-DTPA. In the 1.5 T system, a linear relationship (r(2) > or = 0.95) was demonstrated in the range of 0-5.0 mmol/l Gd-DTPA, and in the 7 T system, a linear relationship (r(2) > or = 0.92) was demonstrated in the range of 0-3.0 mmol/l Gd-DTPA. Additionally, the effect of signal-to-noise on measured concentrations of Gd-DTPA was simulated using MR data of the mixed solutions of Gd-DTPA in plasma and the analytical expression of the pulse sequences. The simulations showed that the concentrations were most sensitive to noise in the GRASS sequence. In conclusion, this study demonstrates a novel approach to quantify accurately the Gd-DTPA concentration directly from MRI signal data using different routine sequences.

Growth disturbances in experimental juvenile arthritis of the dog knee.

In the study of pathophysiological mechanisms in growth abnormalities of the juvenile knee in arthritis an animal model in dogs was developed. Arthritis was induced by intra-articular injections of Carrageenan. Prominent growth changes were enlargement of the distal femoral epiphysis, patellar squaring and decreased endochondral and appositional growth of the distal femur. Generalized osteoporosis of the arthritic limb was present. The induced growth disturbances bear resemblance to the growth abnormalities in juvenile chronic arthritis and hemophilic arthropathy of the knee.