Microbiological aspects of the UK National Institute for Health and Clinical Excellence (NICE) guidance on urinary tract infection in children.

The publication in August 2007 of the UK National Institute for Health and Clinical Excellence (NICE) guidance on urinary tract infection in children provided a fresh and useful review of the management of this condition. However, it has also resulted in some controversy. In particular, the advice to use urgent microscopy for rapid screening of urine in children >or=3 months but <3 years of age has presented practical problems for some laboratories in staffing this service out of hours. Further discussion between microbiologists, paediatricians and primary care doctors regarding this recommendation is required. In addition, the abandoning of routine antibiotic prophylaxis following a first-time urine infection has caused some debate. The evidence around these issues is reviewed, as well as the differences in the laboratory processing and interpretation of paediatric urines compared with urine specimens from adults. General measures to reduce the risk of recurrence are also discussed. As mentioned in the NICE guidance, microbiologists should continue to emphasize the basic principles, particularly the importance of obtaining an accurate diagnosis from a well-collected and well-transported urine specimen.

Regional anatomy of the term human placenta.

We have studied regional anatomical variability in four term placentae, comparing both whole placental regions and intralobar zones and plates. In addition, we have emphasized the need for careful selection of the area to be sampled, rather than strictly randomized sampling of the whole placenta. A unique contribution is our quantitative data for a number of structures of the several intralobar zones and plates. The data confirm the hypothesis that the area best suited to physiological exchange is the central region parabasal plate. The relative homogeneity of the intralobar zones in this area make it a representative area for sampling for various placental studies.

Placental anatomy and diffusing capacity in guinea pigs following long-term maternal hypoxia.

To determine the relation of placental structure to placental diffusing capacity (DPCO), we exposed Hartley guinea pigs to 12 or 14 per cent O2 from day 15 of gestation to near term (64 days). At that time we measured DPCO and fetal body and placental weights. In addition, we used stereological techniques to measure placental parameters important to diffusing capacity. We also used a mathematical model with results from the stereological measurements to predict the diffusing capacity. In the first hypoxic group (E1), measured DPCO decreased 10.1 +/- 3.7 per cent, while that predicted was 2.4 per cent less than control. Total vascular volume decreased 6.6 +/- 3.6 per cent, while tissue volume and mean diffusion distance increased 10.2 +/- 5.6 per cent and 12.9 +/- 7.0 per cent, respectively. In the pair-fed animals, measured DPCO decreased 22.6 +/- 4.6 per cent, while that predicted was 20.0 per cent less than control. There were no significant stereological differences in this group. In the second (E2) hypoxic group, measured DPCO increased 27.2 +/- 7.4 per cent, while that predicted increased 38.2 per cent. For this same group, total vascular volume increased 11.7 +/- 3.0 per cent, and tissue volume and mean diffusion distance decreased 18.2 +/- 4.6 per cent and 17.8 +/- 3.8 per cent, respectively. These results demonstrate the dependence of placental diffusing capacity upon placental structure.

Fetal and uteroplacental heat production in sheep.

To separate heat production of the fetus from that of the placenta, endometrium, and uterine muscle, we measured total uterine heat production first with the fetus intact and then after the umbilical cord was snared and the fetus killed. Heat production was measured with the Fick principle using thermistors chronically implanted in a maternal artery and major uterine vein and a flowmeter placed on the common internal iliac artery. In nine ewes, carrying lambs weighing 4.46 +/- 0.42 (SE) kg, total uterine heat production fell from 10.6 to 2.9 W after fetal death. Uterine blood flow fell progressively to 90% of control levels during the first hour after death. The caloric equivalent for O2 averaged 4.1 cal/ml O2 for the uterus, 2.2 for the uteroplacenta, and 4.6 for the fetus per se. It was not possible to explain these results using a simple model of maternal-fetal heat transfer. Rather, it was necessary to assume an additional pathway for heat transfer between small uterine veins on the surface of the uterus and cooler structures in the maternal abdomen, presumably the ventral abdominal wall.

Cardiac enzyme activities in fetal and adult pregnant and nonpregnant sheep exposed to high-altitude hypoxemia.

We measured pyruvate kinase (PK), citrate synthase (CS), and lactate dehydrogenase (LDH) activities in the right and left ventricles of fetal, maternal, and nonpregnant adult sheep exposed to high altitude (3,820 m) for 112 days and compared them with control groups of animals kept at sea level. Enzymes were assayed by the spectrophotometric appearance of reaction products specific to each enzyme, and activity was expressed as micromoles per minute per gram of wet weight of tissue. In control sheep, CS activity was significantly higher in both ventricles of the pregnant and nonpregnant adult compared with the fetus. However, LDH and PK activities were only higher in the left ventricle of the nonpregnant adult compared with the fetus. Long-term hypoxemia significantly increased LDH activities in fetal (57 and 53%), pregnant adult (29 and 27%), and non-pregnant adult (25 and 24%) right and left ventricles, respectively. CS activities also increased in fetal (90 and 97%), pregnant adult (43 and 39%), and nonpregnant adult (46 and 48%) right and left ventricles, respectively. However, PK activity was not affected by altitude in any group of animals. In the fetal heart, which uses lactate as its primary metabolic fuel, these enzyme changes may help enhance aerobic energy production during hypoxemia. In the adult heart, which relies on free fatty acids as well as glucose for energy production, the significance of these enzyme changes is less clear.

Computer model of fetal-maternal heat exchange in sheep.

We constructed and used a mathematical model of maternal-fetal heat exchange in the sheep to explore the effects of changes in certain parameters on steady-state fetal temperatures and to determine whether the fetus in the model has any potential to control its own temperature. The model took into account both fetal and placental heat production and exchange of heat in the placenta, across the fetal skin, via amniotic fluid, and through the uterine wall. The maternal ewe was assumed to be a constant temperature heat sink. Changes in placental or fetal heat production were calculated to change the ratio of heat exiting across the placenta or fetal skin significantly but to have little effect on fetal core temperature, e.g., a rise of only 0.8 degrees C was predicted after a twofold increase in fetal heat production. Fetal placental blood flow was calculated to affect fetal temperature the most of any flow, a reduction to zero causing fetal temperature to rise 5.0 degrees C. Changes in heat conductances between fetal skin and amniotic fluid, or between amniotic fluid and uterine wall, had minimal effect on fetal temperature. From the model calculations here and because heat exchange within the sheep placenta has previously been calculated to be extremely efficient, we conclude that the fetal sheep has little ability to control its temperature by changes in heat dissipated through extraplacental pathways. Thus the model predicts an effective heat clamp that closely links fetal to maternal temperature.

Effects of isoproterenol on the cardiovascular system of fetal sheep exposed to long-term high-altitude hypoxemia.

We exposed fetuses to high-altitude (3,820 m) hypoxemia from 30 to 130 days gestation, when we measured fetal heart rate, right and left ventricular outputs with electromagnetic flow probes, and arterial blood pressure during an isoproterenol dose-response infusion. We also measured the distribution of cardiac output with radiolabeled microspheres during the maximal isoproterenol dose. Baseline fetal arterial blood pressure was higher in long-term hypoxemic fetuses (50.1 +/- 1.3 vs. 43.4 +/- 1.0 mmHg) but fell during the isoproterenol infusion to 41.3 +/- 1.4 and 37.5 +/- 1.4 mmHg, respectively, at the highest dose. Heart rate was the same in both groups and did not differ during isoproterenol infusion. Baseline fetal cardiac output was lower in the hypoxemic group (339 +/- 18 vs. 436 +/- 19 ml.min-1.kg-1) due mainly to a reduction in right ventricular output. During the isoproterenol infusion, right ventricular output increased to the same extent in both hypoxemic and normoxic fetuses (approximately 35%); however, left ventricular output increased only approximately 15% in the hypoxemic group compared with approximately 40% in the normoxic group. The percent change in individual organ blood flows during isoproterenol infusion in the hypoxemic groups was not significantly different from the normoxic group. All of the mechanisms that might be responsible for the differential response of the fetal left and right ventricles to long-term hypoxia are not understood and need further exploration.

Heat transfer pathways between fetal lamb and ewe.

Heat produced by the fetus exists to the mother by one of two principal routes: by fetal-maternal exchange in the placenta or through the fetal skin to the amniotic fluid and uterine wall. We measured heat conductances along each pathway to estimate the fraction of total heat exiting each route. Thermistors were placed in the fetal aorta, two different sites in the amniotic fluid, and in a maternal artery. Five days after surgery we injected a total of 280 ml of ice-cold saline into the two separate amniotic fluid sites during a 45-s interval and measured the temperature response for the next hour. After one or two such injections the fetus was killed to cut off umbilical blood flow, and the experiment was repeated to measure the heat fluxes in the absence of placental heat exchange. Experimentally obtained temperature curves were compared with the predictions of a mathematical model. Heat conductances of the skin and uterine wall, as well as the fetal heat production, were estimated in the model using least-squares parameter optimization. In 10 fetal lambs, weighing 3.73 +/- 0.40 (SE) kg, total fetal heat production averaged 3.75 +/- 0.33 W X kg-1. The heat conductance of the uterine wall, 6.6 +/- 0.8 W X degrees C-1, was lower than that of the fetal skin, 10.2 +/- 1.0, and of the placenta, 25.7 +/- 2.9 W X degrees C-1, temperature gradient. We estimated that 84.5% of total fetal heat production exists by fetal-maternal exchange in the placenta with the remaining 15.5% exiting through the fetal skin.

Hypertension: a cause of growth impairment.

The effects of high blood pressure on growth are not fully understood and while hypertension may be associated with failure to thrive, hypertension causing failure to thrive in children is poorly documented. We describe four children presenting with failure to thrive due to hypertension consequent to various aetiologies. Control of hypertension with appropriate therapy resulted in improved growth. The exact pathogenesis of failure to thrive in hypertensive children is not known. These cases demonstrate the importance of careful measurement of blood pressure in children with failure to thrive.

Oxygen dose-response curve of cardiac papillary muscle from fetal and nonpregnant adult sheep exposed to long-term, high-altitude hypoxemia.

OBJECTIVE: We tested the hypothesis that hearts of fetal and nonpregnant adult sheep exposed to long-term hypoxemia would be able to sustain higher contractile function during exposure to acute hypoxia than hearts from normoxic animals. METHODS: Pregnant and nonpregnant sheep were exposed to high altitude (3820 m) for 100 days. Right and left ventricular papillary muscle strips were obtained from fetuses and nonpregnant adults, mounted in an isolated bath system, stimulated electrically and subjected to acute hypoxia in a dose response manner. Measurements were made of maximum tension production (Tmax), maximum rate of tension development (+dT/dtmax), maximum rate of relaxation (-dT/dtmax), time to peak tension, and duration of contraction. Results were compared to papillary muscle from a normoxic group of animals. RESULTS: Baseline values (95% O2 + 5% CO2 bubbled in the bath) of Tmax and +/- dt/dtmax for each ventricle were greater in adults than fetuses in both normoxic and long-term hypoxemic groups. During hypoxia (at 40 and 20% O2) Tmax and +/- dT/dtmax, were all maintained at significantly higher values in papillary muscle from long-term hypoxemic fetuses than in papillary muscle from normoxic fetuses. Duration of contraction and time to peak tension did not differ between the normoxic and hypoxemic groups. In both ventricles of the long-term hypoxemic adult, Tmax and +/- dT/dtmax, as well as duration and time to peak tension, were significantly higher than in normoxic adults, but only at the lowest level of hypoxia (20% O2). CONCLUSIONS: Contrary to the original hypothesis, heart muscle from both fetal and adult sheep that had been exposed to long-term hypoxemia could maintain contractile function better during acute hypoxia. The responsible mechanisms are not clearly understood.

Effects of long-term high-altitude hypoxia on isolated fetal ovine coronary arteries.

OBJECTIVE: To examine the effects of long-term high-altitude hypoxia on the contractile properties of isolated fetal coronary arteries. METHODS: Maximal contractile responses (T(max)) to 90 mmol/L KCl and the thromboxane A(2) mimetic U46619 were measured in proximal (PLCx) and distal left circumflex (DLCx), left anterior descending (LAD), and right coronary arterial (RCA) rings from high-altitude and control fetuses. Paired studies were conducted with and without nitric oxide synthase (NOS) inhibitors, Nomega-nitro-L-arginine and Nomega-nitro-L-arginine ester. RESULTS: In high-altitude fetuses, 90 mmol/L KCl T(max) responses in both intact and NOS-blocked rings decreased by approximately 62% in PLCx, approximately 59% in DLCx, approximately 57% in LAD, and approximately 47% in RCA (n = 9-18/group; P <.05). High-altitude vessels also exhibited decreased sensitivity to U46619. NOS blockade potentiated T(max) to U46619 in the high-altitude RCA segments and augmented T(max) to U46619 in high-altitude RCA compared with its treated control counterpart (P <. 05). CONCLUSION: These results suggest that nitric oxide influences the pharmacologic responsiveness of the RCA to U46619. Furthermore, long-term high-altitude hypoxia significantly alters the contractile capabilities of fetal coronary arteries. These observations may partially explain the maintained redistribution of cardiac output to the fetal heart during exposure to long-term high-altitude hypoxia.

Ca(2+) sensitivity of fetal coronary arteries exposed to long-term, high-altitude hypoxia.

OBJECTIVE: To determine the contribution of decreased calcium responsiveness of fetal coronary arteries to decreased contractile responses to potassium and the thromboxane A(2) analogue U46619 in these arteries after exposure to chronic hypoxemia. METHODS: Concentration-response curves to Ca(2+) in beta-escin-permeabilized left circumflex (LCx), left anterior descending (LAD), and right coronary artery (RCA) rings from high-altitude (HA) and control (CON) fetuses were measured. In a second set of beta-escin-permeabilized coronary artery rings, the effect of U46619 on Ca(2+) sensitivity was tested. RESULTS: Maximum Ca(2+)-activated force (T(max)) was decreased in HA LCx (CON 0.091+/-0.010 versus HA 0.057+/-0.006 g/cm(2); P<.05) and HA LAD (CON 0.065+/-0.012 versus HA 0.031+/-0.007 g/cm(2); P <.05). No significant difference was observed in the RCA. There was no change in the pD(2) (-log EC(50)) values between CON and HA coronary rings. The Ca(2+) sensitizing effect of U46619 on submaximal Ca(2+)-activated force was lower only in the HA LCx (CON 0.044+/-0.010 versus HA 0.023+/-0.006 g/cm(2) at 10(-5) mol/L; P<.05). CONCLUSION: These results indicate that maximum tension development in response to Ca(2+) was decreased in the HA LCx and LAD but not the RCA; however, Ca(2+) sensitivity of the contractile apparatus was unaltered in all of them. Decreased Ca(2+) responsiveness may partially explain the decreased contractile capability of fetal LCx and LAD during long-term, high-altitude intrauterine hypoxemia.

Abdominal aortic aneurysms in children.

Abdominal aortic aneurysms are rare in children. Causes include mycotic aneurysms, vasculitides (eg, Takayasu's arteritis), connective tissue diseases (eg, Marfan's syndrome, Ehlers-Danlos syndrome, and tuberous sclerosis) and traumatic false aneurysms. Four cases are described. Case 1 was a 12-year-old boy who presented with an acute unheralded rupture of the subdiaphragmatic aorta accompanied by lower limb paralysis and ischemia. Attempted repair failed because of extensive friability of the large arteries. Histological evaluation confirmed cystic medial necrosis despite Marfanoid phenotype. Cases 2 and 3 were boys aged 12 and 11 with Takayasu's arteritis who presented with hypertensive encephalopathy and heart failure. Although both had involvement of the origins of the renal arteries, one aneurysm was predominantly suprarenal and the other infrarenal. Currently both children are being managed successfully with antihypertensive therapy. Case 4 was a 5-year-old girl who presented with hypertension and a pulsatile abdominal mass after treatment of infective endocarditis 18 months previously. Arteriography and three-dimensional computed tomography confirmed an aneurysm (6 x 5 x 4 cm) arising from the aorta and involving the right renal artery. Aneurysmectomy, removal of a small ischemic right kidney, and Gore-Tex grafting resulted in cure of the hypertension and uneventful recovery. The present series confirms that rupture is a fatal complication, renovascular complications are common, and medical control of hypertension is an essential part of management. Management strategies need to be highly individualized, and may be successful without surgical intervention. Close clinical and ultrasound follow-up of those managed nonoperatively is essential.

Measurement of blood flow with radiolabeled microspheres in reflected mucogingival flaps in cats.

To quantify and compare blood flow in maxillary mucogingival flaps, a total of 16 cats (32 mucogingival specimens) were divided into two groups. In group I the blood flow in attached or reflected maxillary tissues were measured. In Group II the effects on blood flow were measured in reflected tissues after the injection of the following solutions: (1) saline solution; (2) 2% lidocaine plain; (3) 2% lidocaine with 1:50,000 epinephrine; (4) no injection. After an injection of 153 Gadolinium microspheres into the left ventricle of the heart, the tissues were harvested and placed in a gamma counter. Group I had a mean blood flow value of 34.4 ml/min/100 gm of tissue for the unreflected samples and 152.3 ml/min/100 gm of reflected tissue. The levels of blood flow in tissue samples in group II results were: no injection (control), 41.2 ml/min/100 gm; saline solution, 46.8 ml/min/110 gm; 2% lidocaine with 1:50,000 epinephrine, 60.6 ml/min/100 gm; and 2% lidocaine plain, 90.2 ml/min/100 gm. On the basis of these results it appears that reflection of gingival tissue and injection of 2% lidocaine plain induces increased blood flow 90 minutes postoperatively.

A randomized, clinical evaluation of the safety and efficacy of a novel oral irrigator.

PURPOSE: To evaluate the safety and efficacy of the Braun Oral-B OxyJet (MD15) Oral Irrigator when used as an adjunct to manual brushing. MATERIALS AND METHODS: 64 subjects with mild-to-moderate gingivitis entered this randomized, parallel-group, examiner-blind 8-week study. Subjects were assigned to use either the MD15 and a manual brush, or a manual brush alone. Both groups brushed twice daily; the MD15 subjects, in addition to brushing, also used the irrigator in the evening. Subjects were scored at baseline, week 4 and week 8 at up to 168 oral sites for gingival inflammation (modified gingival index), gingival bleeding (angular bleeding index), and plaque (modified plaque index). RESULTS: No adverse events related to study treatment were reported. Use of the MD15 in conjunction with manual brushing resulted in significant (P < 0.05) decreases from baseline in the plaque index at week 8, the gingival index at week 4, and the bleeding index at weeks 4 and 8. The gingival index was also decreased from baseline at week 8, but this was not statistically significant (P = 0.069). The control group also showed significant decreases from baseline for the gingival index at week 8 and the bleeding index at weeks 4 and 8, but plaque scores were not significantly reduced. Although use of the MD15 plus brushing significantly reduced plaque levels from baseline, while brushing alone did not, the difference between the two groups did not achieve statistical significance (P = 0.065). Differences between the groups with respect to the gingival and bleeding indices were also not statistically significant. It is concluded that use of the OxyJet Oral Irrigator in conjunction with manual brushing is safe, reduces plaque and improves gingival health.

Acute renal tubular dysfunction in association with Salmonella enteritidis.

A thirteen-year-old boy presented with acute renal tubular dysfunction after an infection with salmonella enteritidis. The child recovered following treatment with ciprofloxacin for a week.

Efficacy of a chlorine dioxide-containing mouthrinse in oral malodor.

Studies have suggested that when chlorine dioxide is contained in a mouthrinse, it neutralizes volatile sulfur compounds in mouth air. The efficacy of a chlorine dioxide-containing mouthrinse in the reduction of oral malodor was evaluated in a randomized, controlled, double-blind, parallel group study of 31 men and women. Subjects with a maximum odor pleasantness score of < or = -1 (slightly unpleasant/stale) on a 7-point ordinal scale at both screening and baseline were randomized to treatment with the chlorine dioxide-containing rinse (n = 16) or distilled water (negative control) (n = 15). Oral malodor was evaluated at baseline (prerinse) and at 2, 4, 8, 24, 48, 72, and 96 hours postrinse by both a trained, previously calibrated panel of organoleptic judges and a factory-calibrated portable sulfide monitor. The sulfide monitor measured concentrations of volatile sulfur compounds in the subjects' mouth air 3 minutes after completion of the organoleptic assessment at each time point. The correlation between the organoleptic assessments and log-transformed sulfide monitor values was evaluated. With the chlorine dioxide mouthrinse, a statistically significant improvement in odor pleasantness, reduction in odor intensity, and reduction in oral volatile sulfur compound concentrations compared to the water control were evident at 2 hours postrinse and persisted through 8 hours postrinse. The mean (+/- SD) odor pleasantness improved from -1.25 +/- 0.31 at baseline to -0.73 +/- 0.33 at 2 hours postrinse in the chlorine dioxide group compared to -1.40 +/- 0.38 at baseline to -1.31 +/- 0.67 at 2 hours in the control group (P < 0.01). Odor pleasantness reached its maximum change from baseline to 0.63 +/- 0.45 at 8 hours postrinse. The mean (+/- SD) log-transformed sulfide monitor measurement decreased from 5.40 +/- 0.29 at baseline to 5.17 +/- 0.13 at 2 hours postrinse in the chlorine dioxide group, but increased from 5.47 +/- 0.40 at baseline to 5.56 +/- 0.54 at 2 hours in the control group (P < 0.01). As measured by the sulfide monitor, the mean volatile sulfur compound concentration in the chlorine dioxide group reached its minimum level at 8 hours postrinse (change from baseline in the log-transformed Halimeter measurement of -0.35 +/- 0.31). Thus, this study demonstrates that a one-time use of a chlorine dioxide-containing mouthrinse significantly improves mouth odor pleasantness, reduces mouth odor intensity, and reduces volatile sulfur compound concentrations in mouth air for at least 8 hours after use.

Children with nephrotic syndrome have greater bone area but similar volumetric bone mineral density to healthy controls.

BACKGROUND: Glucocorticoid use has been associated with an increased fracture risk and reduced bone mineral density (BMD), particularly in the trabecular compartment. However the contribution of the underlying inflammatory disease process to these outcomes is poorly understood. Childhood nephrotic syndrome (NS) typically follows a relapsing-remitting course often requiring recurrent courses of glucocorticoids, but with low systemic inflammation during remission. NS therefore represents a useful clinical model to investigate the effects of glucocorticoids on BMD and bone geometry in childhood. METHODS: Children with NS were compared to age and sex matched healthy controls. Body composition and areal BMD (whole body, lumbar spine and hip) were assessed by DXA. Peripheral quantitative computed tomography (pQCT) scans were obtained at metaphyseal (4%) and diaphyseal (66%) sites of the tibia to determine volumetric BMD and bone cross-sectional geometry. Lifetime cumulative glucocorticoid exposure was calculated from medical records. RESULTS: 29 children with NS (55% male, age 10.7±3.1years) were compared to 29 healthy controls (55% male, age 11.0±3.0years). The children with NS were of similar height SDS to controls (p=0.28), but were heavier (0.65±1.28SDS vs -0.04±0.89SDS, p=0.022) and had greater body fat percentage SDS (0.31±1.01 vs -0.52±1.10, p=0.008). Tibial trabecular and cortical vBMD were similar between the two groups but bone cross-sectional area (CSA) was significantly greater in children with NS at both the metaphysis (954±234mm(2) vs 817±197mm(2), p=0.002) and diaphysis (534.9±162.7mm(2) vs 463.2±155.5mm(2), p=0.014). Endosteal and periosteal circumferences were greater in children with NS than controls (both p<0.01), resulting in reduced cortical thickness (2.4±0.7mm vs 2.8±0.7mm, p=0.018), but similar cortical CSA (p=0.22). The differences in cortical geometry were not statistically significant when weight was included as a confounding factor. There were no associations between cumulative steroid exposure, duration of NS or number of relapses and any bone parameter. CONCLUSIONS: Tibial bone CSA is increased in children with NS. We speculate that this is a compensatory response to increased body weight. Defects in trabecular BMD were not identified in this cohort of children with NS.