Association between urodynamic parameters and urine neutrophil gelatinase-associated lipocalin concentrations in children with neuropathic bladders.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a marker of acute kidney injury, and has been shown to be a sensitive marker of renal damage in urinary tract obstruction. Children with neurogenic bladders are at risk of renal damage as a result of increased pressure within the urinary system. A marker of upper tract deterioration in this population would be useful to guide management. OBJECTIVE: The aim of the study is to compare urinary NGAL (uNGAL) concentrations between children who have elevated and normal detrusor pressure and between those with low and normal compliance, on urodynamics. STUDY DESIGN: This is a cross-sectional study of children with neurogenic bladder who underwent routine urodynamics from August 2015 to March 2016. Patients with positive urine cultures from the time of urodynamics were excluded from analysis. Urine was obtained from the time of urodynamics for uNGAL measurement. Urodynamics were reviewed. High pressure is defined as a detrusor pressure of 40 cm of water or greater at the volume where catheterization is normally performed. Compliance was calculated at the volume where catheterization is performed. RESULTS: A total of 89 patients were included (low pressure, n = 73; high pressure, n = 16 and low compliance, n = 41; normal compliance, n = 40). Median uNGAL concentrations were not different between patients with low and high pressure, but there was a higher median uNGAL concentration in patients with normal compliance compared with those with low compliance. There was no correlation between maximum detrusor pressure and uNGAL concentration, but there was a moderate relationship between compliance and uNGAL concentration (rs = 0.43, p < 0.01 for non-normalized uNGAL and rs = 0.30, p < 0.01 for normalized uNGAL). DISCUSSION AND CONCLUSION: There is an increase in uNGAL concentrations in patients with normal compliance compared with those with low compliance, but no difference between patients with low or high pressure.

Variation among subspecialists in the diagnosis of urinary tract infection in children with neurogenic bladders.

BACKGROUND: Children with neurogenic bladders who require clean intermittent catheterization (CIC) frequently have bacteriuria. However, there is no consensus on what constitutes at urinary tract infection (UTI) in this population. Multiple subspecialists are often involved in the management of these patients, although they are frequently cared for by hospitalists when admission is required. OBJECTIVE: The objective of this study was to describe the variability in opinion between subspecialists in the diagnosis of a UTI in CIC-dependent children. STUDY DESIGN: A scenario-based survey was distributed to physicians in the divisions of urology, nephrology, and hospital medicine at a single free-standing children's hospital. Respondents rated their degree of confidence on whether a specific scenario represented UTI or colonization on an 11-point Likert Scale. Median responses were compared with the Kruskal-Wallis test with pair-wise comparisons. RESULTS: Back/flank pain, abdominal pain, and vomiting were the most common symptoms that were suggestive of a UTI in a non-febrile child. There was no single symptom chosen that was the most suggestive of a UTI in CIC-dependent child. There was significant variability between specialists in the diagnosis of UTI in specific clinical scenarios on the survey. Hospitalists were significantly less confident about the diagnosis of a UTI than urologists in two of the clinical scenarios. CONCLUSIONS: Standardization and implementation of consensus criteria for UTI in this high-risk population is needed.

Utility of a routine urinalysis in children who require clean intermittent catheterization.

BACKGROUND: Children who require clean intermittent catheterization (CIC) frequently have positive urine cultures. However, diagnosing a urinary tract infection (UTI) can be difficult, as there are no standardized criteria. Routine urinalysis (UA) has good predictive accuracy for UTI in the general pediatric population, but data are limited on the utility of routine UA in the population of children who require CIC. OBJECTIVE: To determine the utility of UA parameters (e.g. leukocyte esterase, nitrites, and pyuria) to predict UTI in children who require CIC, and identify a composite UA that has maximal predictive accuracy for UTI. METHODS: A cross-sectional study of 133 children who required CIC, and had a UA and urine culture sent as part of standard of care. Patients in the no-UTI group all had UA and urine cultures sent as part of routine urodynamics, and were asymptomatic. Patients included in the UTI group had growth of ≥50,000 colony-forming units/ml of a known uropathogen on urine culture, in addition to two or more of the following symptoms: fever, abdominal pain, back pain, foul-smelling urine, new or worse incontinence, and pain with catheterization. Categorical data were compared using Chi-squared test, and continuous data were compared with Student's t-test. Sensitivity, specificity, and positive and negative predictive values were calculated for individual UA parameters, as well as the composite UA. Logistic regression was performed on potential composite UA models to identify the model that best fit the data. RESULTS: There was a higher proportion of patients in the no-UTI group with negative leukocyte esterase compared with the UTI group. There was a higher proportion of patients with UTI who had large leukocyte esterase and positive nitrites compared with the no-UTI group (Summary Figure). There was no between-group difference in urinary white blood cells. Positive nitrites were the most specific (84.4%) for UTI. None of the parameters had a high positive predictive value, while all had high negative predictive values. The composite model with the best Akaike information criterion was >10 urinary white blood cells and either moderate or large leukocyte esterase, which had a positive predictive value of 33.3 and a negative predictive value of 90.4. CONCLUSION: Routine UA had limited sensitivity, but moderate specificity, in predicting UTI in children who required CIC. The composite UA and moderate or large leukocyte esterase both had good negative predictive values for the outcome of UTI.

Production of prostaglandins E and Falpha by corpora lutea, corpora albicantes and stroma from the human ovary.

This study has shown that corpora lutea, stromal tissue and corpora albicantes from human ovaries contain prostaglandin E (PGE) and PGFalpha, and that the two former tissues can synthesize these prostaglandins during incubation. Enhanced syntheses, especially of PGE, occurred on adding arachidonic acid to the incubation medium, and the presence of prostaglandin synthetase activity was conclusively demonstrated. In corpora lutea obtained during the early and mid-luteal phase, the mean concentrations of PGE and PGFalpha were 34.3 and 9l9 ng/g respectively (mean ratio PGE:PGFalpha = 3.7); similar values were found in three corpora lutea from women at 10-12 weeks of pregnancy. All these corpora lutea contained appreciable amounts of progesterone and oestradiol-17beta. Prostaglandin levels were generally lower in corpora lutea obtained during the late luteal phase, although the PGE:PGFalpha ratio had increased to a mean value of 8.4. In corpora albicantes, the concentrations of both PGE and PGFalpha were significantly higher than the levels found in corpora lutea (P less than 0.01), whilst the mean ratio of PGE:PGFalpha had fallen significantly to 1.8 (P less than 0.01). Prostaglandin levels in stromal tissue varied considerably between individuals. The mean values were significantly lower than those of the corpora albicantes (P less than 0.01) but not significantly different to corpora lutea at any stage. These findings are discussed in relation to the possible role of prostaglandins in ovarian steroidogenesis and corpus luteum regression in man.

Human amnion metabolism. I. In vitro maintenance.

The energy stores of human term amnion include glycogen (2.2 +/- 0.3 mumoles of glucose per gram, mean +/- S.E.) and ATP (0.13 +/- 0.2 MM.). Histologic structure and biochemical functions were preserved during incubations of amnion for 120 minutes at 37 degrees C. in a defined medium simulating amniotic fluid; glycogen concentrations were maintained at control values, and the concentration of ATP usually remained at 85 to 100 per cent of control values. Glucose utilization during the first 60 minutes of incubation was linear at a rate of 70.0 +/- 3.0 nmoles per minute per gram of tissue. It is concluded that amnion is a highly metabolically active tissue that can be maintained in a viable state in a suitable medium.

Human amnion metabolism. II. Incorporation of fatty acids into tissue phospholipids in vitro.

The rate of incorporation of 3H-arachidonic acid and 14C-palmitic acid into 15 term amniotic membranes was studied during incubation of tissues in an artificial amniotic fluid medium. Phospholipids were extracted from the amnions, separated by thin-layer chromatography, and both the radioactivity and the phosphorus associated with each phospholipid species were determined. The distribution of amnion phospholipids was: lecithin, 47 per cent; phosphatidyl ethanolamine, 30 per cent; sphingomyelin, 7 per cent; phosphatidyl inositol, 5 per cent; lysolecithin, 4 per cent; and other phospholipids, 6 per cent. During incubation, the specific activities of the phospholipids became maximal after 2 hours and remained constant for at least the next 2 hours. Arachidonic acid was incorporated mainly into lecithin (53 per cent) and phosphatidyl ethanolamine (27 per cent) whereas palmitic acid was incorporated mainly into lecithin (70 per cent). Incorporation of fatty acids was 33 per cent higher in amnions obtained after vaginal delivery than in those obtained before labor. From the known fatty acid composition of amnion phospholipids, it is concluded that there is a high rate of turnover of arachidonic acid relative to palmitic acid in lecithin.

Production of prostaglandin Falpha in ewes following luteal regression induced with a prostaglandin analogue, Estrumate (cloprostenol; I.C.I. 80996).

A single injection (100 mug i.m.) of Estrumate (I.C.I. 80996) was used to induce luteal regression on day 8 of the estrous cycle in 3 sheep. Progesterone levels in the utero-ovarian vein and femoral artery had fallen within 6 h to less than 50% of the concentrations seen before injection of the analogue. Luteolysis was not associated with endogenous production of PGF. The concentration of PGF in the uteroovarian vein began to increase 27-39 h after the administration of Estrumate, reaching a mean maximum concentration of 1455pg/ml 48 h after Estrumate. The mean concentration of PGF in the utero-ovarian vein between 36-69 h after Estrumate was significantly greater than during the 24 h before Estrumate (control period) or during the 0-30 h immediately after injection (both P less than 0.001). The maximum secretion of estradiol and the pre-ovulatory LH peak occurred during the period of elevated PGF concentrations in the utero-ovarian veins. The possible importance of endogenous PGF production at this time is discussed.

Parturition in the sheep.

Parturition in sheep is initiated by a sharp rise in the rate of secretion of cortisol by the fetal adrenal. Increased secretion is due partly to enhanced responsiveness to corticotropin (ACTH) and partly to increased fetal concentrations of corticotropin. Cortisol acts on placental enzymes active in the biosynthesis of oestrogens from progesterone. Thus placental secretion of oestrogen increases and that of progesterone decreases. This change in the ratio of oestrogen: progesterone, particularly the rise in oestrogen, stimulates release of prostaglandin F2alpha (PGF2alpha) from the maternal placenta and to a lesser extent from the myometrium. PGF2alpha enhances the myometrial response to oxytocin and, after a latent period, stimulates contractions. The onset of parturition is normally associated with softening of the cervix, the mechanism of which is uncertain. Uterine contractions in the presence of a distensible cervix lead to parturition.

Prepartum maturation of the lung in fetal sheep: relation to cortisol.

We studied the relationship of certain fetal and maternal hormones to indicators of lung maturation in 12 fetal lambs delivered at gestational ages (GA) of 123-149 days. Maternal estrogen, maternal progesterone, and fetal prolactin did not correlate with GA or the indicators of fetal lung maturation. Fetal cortisol (range 4-165 ng X ml-1) increased with advancing GA (r = 0.747, P less than 0.01). All of the following showed a wide range of late gestation and showed a significant positive correlation with fetal cortisol: lung volumes at 40 cmH2O and 10 cmH2O on the deflation during air pressure-volume studies; saturated phosphatidylcholine (SPC) in lung tissue and in lavage fluid expressed both as mg X g-1 of wet lung and as percent of total phospholipids (%PL); total SPC (lung tissue plus lavage fluid): and SPC in lavage fluid as percent of total SPC. Lung DNA correlated inversely with GA and cortisol. All variables (except lavage fluid SPC as %PL) correlated more closely with cortisol than GA. Morphological development of lung was also related more closely to cortisol than GA. These results suggest that functional lung maturity is attained late in gestation and that endogenous cortisol is an important physiological factor in control of fetal lung maturation.

Pulmonary maturation in the hypophysectomised ovine fetus. Differential responses to adrenocorticotrophin and cortisol.

Pulmonary maturation in six ovine fetuses hypophysectomised by a cryosurgical method at 0.7-0.8 of pregnancy and delivered by hysterotomy at 152.2 +/- 2.9 (SD) days was compared with that in seven control fetuses delivered at 144.5 +/- 3.5 days. Both the wet and the dry weight of the lungs was less in the hypophysectomised fetuses but total DNA did not differ. Lung volumes at 40 cm of H2O and at 5 cm of H2O on deflation in hypophysectomised fetuses were less than one-third that of controls. Saturated phosphatidylcholine, as an estimate of surfactant, was lower in both lung tissue and lavage fluid. A further group of hypophysectomised fetuses was infused intravenously either with cortisol at 1 mg/h for 72 h (n = 6), or with ACTH1-24 at 5 microgram/h for 84 h (n = 6) before delivery at 155.0 +/- 2.1 days and 154.2 +/- 3.9 days respectively. None of the indices of pulmonary maturation in the cortisol-treated fetuses differed from those in untreated hypophysectomised fetuses whereas values for lung volumes at 40 and 5 cm of H2O in ACTH-treated fetuses were more than twice those of untreated hypophysectomised fetuses and did not differ significantly from controls. In addition, the amount of saturated phosphatidylcholine in lavage fluid was greater in ACTH-treated fetuses (0.13 +/- 0.10 mg/g) than in untreated hypophysectomised fetuses (0.04 +/- 0.48 mg/g). Lung volume at 40 cm of H2O in four fetuses that were thyroidectomised at the time of hypophysectomy responded to ACTH as in hypophysectomised fetuses with intact thyroids but other indices were unaffected. We conclude that hypophysectomy retards pulmonary maturation in fetal sheep. Since ACTH restores distensibility and increases alveolar surfactant in the absence of other pituitary hormones it is likely that ACTH has a major role in lung maturation. The lack of response to cortisol suggests that the effect of ACTH is not mediated only by circulating cortisol.