Effects of diet and exercise on obesity-related vascular dysfunction in children.

BACKGROUND: The prevalence of obesity in both adults and children is increasing rapidly. Obesity in children is independently associated with arterial endothelial dysfunction and wall thickening, key early events in atherogenesis that precede plaque formation. METHODS AND RESULTS: To evaluate the reversibility of obesity-related arterial dysfunction and carotid intima-media thickening by dietary and/or exercise intervention programs, 82 overweight children (body mass index, 25+/-3), 9 to 12 years of age, were randomly assigned to dietary modification only or diet plus a supervised structured exercise program for 6 weeks and subsequently for 1 year. The prospectively defined primary end points were ultrasound-derived arterial endothelial function (endothelium-dependent dilation) of the brachial artery and intima-media thickness of common carotid artery. At 6 weeks, both interventions were associated with decreased waist-hip ratio (P<0.02) and cholesterol level (P<0.05) as well as improved arterial endothelial function. Diet and exercise together were associated with a significantly greater improvement in endothelial function than diet alone (P=0.01). At 1 year, there was significantly less thickening of the carotid wall (P<0.001) as well as persistent improvements in body fat content and lipid profiles in the group continuing an exercise program. Vascular function was significantly better in those children continuing exercise (n=22) compared with children who withdrew from the exercise program (n=19) (P<0.05). CONCLUSIONS: Obesity-related vascular dysfunction in otherwise healthy young children is partially reversible with diet alone or particularly diet combined with exercise training at 6 weeks, with sustained improvements at 1 year in those persisting with diet plus regular exercise.

Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation.

PURPOSE: Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with endothelial dysfunction that can be improved with short-term folic acid supplementation. The current study aimed to assess whether folic acid supplementation could produce longer-term improvements in homocysteine levels and arterial endothelial function. SUBJECTS AND METHODS: Twenty-nine healthy adults with hyperhomocysteinemia were selected from 89 volunteers enrolled in a community-based atherosclerosis screening project. All subjects were given folic acid (10 mg/d) for 1 year. Fasting plasma homocysteine levels were measured by high-performance liquid chromatography. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound. RESULTS: Folic acid supplementation for 1 year was associated with a significant increase in mean (+/-SD) plasma folate levels (24 +/- 5 nmol/L to 40 +/- 5 nmol/L; P < 0.001) and a significant decline in homocysteine levels (9.0 +/- 1.7 micromol/L to 7.9 +/- 2.0 micromol/L; P < 0.001). Flow-mediated dilation also improved significantly, from 7.4% +/- 2.0% to 8.9% +/- 1.5% (P <0.0001), but there was no change in nitroglycerin-induced (endothelium-independent) responses. CONCLUSIONS: These results demonstrate that long-term folic acid improves arterial endothelial function and has potential implications for the prevention of atherosclerosis in adults with hyperhomocysteinemia.

Doppler waveform of the ureteric jet in pregnancy.

We have shown that the function of the bladder vesicoureteric junction (VUJ) can be studied by the Doppler waveform of the ureteric jet, and this reflects the active sphincteric mechanism of the VUJ. We wished to investigate if the hormonal changes of pregnancy cause any alteration of VUJ function. A total of 107 pregnant women and 375 nonpregnant women were recruited. Three scans, 20 and 32 weeks of gestational age and 3 months postpartum, were done. The occurrence of a monophasic waveform in the nonpregnant group was 1.9%. In the pregnancy group, this was 18.7%, 41.1% and 1.6% at 20, 32 weeks of gestational age and 3 months postpartum, respectively. The difference in occurrence of the monophasic waveforms was statistically significant (both p = 0.0005 at 20 and 32 weeks). This suggests an adverse hormonal effect on the vesicoureteric junction during pregnancy, and may be a factor in the increased risk of UTI in pregnancy.

Ureteric jet in renal transplantation patient.

We have made a case for an active sphincteric mechanism at the VUJ modifying the ureteric jet Doppler waveform. The transplanted ureter does not have a normal VUJ, but retains inherent peristalsis. This study was to document any difference in the transplanted ureteric jet Doppler pattern. A total of 55 transplant patients and 817 healthy subjects were recruited. The Doppler waveform of the transplanted ureter is distinctly different from that of the healthy adult ureter. There are two major patterns: a short monophasic waveform is the most common (66.1% vs. 2.6% in healthy ureters). Less common is a longer, more phasic, pattern, which, however, does not resemble the patterns of the healthy ureter. This supports the hypothesis that the mode of action at the VUJ is sphincteric, because this is lost with transplantation, and ureteric drainage reverts to a simple unmodified pattern.

The ureteric jet doppler waveform as an indicator of vesicoureteric sphincter function in adults and children. An observational study.

The nature of the action of the vesicoureteric junction (VUJ) in humans is still controversial. We were interested in the reasons why the jet consists of several peaks. We hypothesised that the modification of the jet into a variable number of peaks is the result of an active sphincter mechanism at the VUJ. A total of 1,010 subjects of all ages and both genders were recruited into this study. The Doppler waveform of the jet was recorded bilaterally. We could identify six basic patterns of ureteric jet according to the number of peaks: monophasic, biphasic, triphasic, polyphasic (four or more peaks), square and continuous. By analysing the duration, maximum peak velocity and initial slope of the first four patterns, a mechanism of action of an active VUJ sphincter could be postulated. Furthermore, the basic patterns could be assigned to three modes of ureteric actions: the square and continuous are only seen during diuretic stress; the biphasic, triphasic and polyphasic patterns are variations of the adult physiological steady-state mode, and the monophasic is distinctly different and represents the immature mode.

Immature ureteric jet doppler patterns and urinary tract infection and vesicoureteric reflux in children.

The Doppler waveform of the ureteric jet is the result of modification of ureteric peristalsis by an active sphincteric mechanism of the vesicoureteric junction (VUJ). The monophasic pattern is associated with immaturity. This study set out to see the correlation between this immature pattern with urinary tract infection (UTI) and vesicoureteric reflux (VUR) in children. Ureteric jets of 241 healthy children and 98 children with UTI were studied. The monophasic pattern was found in 29% of healthy children overall, but varied greatly according to age. The monophasic pattern was virtually universal in the first 6 months of life, dropping to below 15% in late childhood. This immature pattern was more commonly seen in the UTI (73.5%) and VUR (90.5%) groups than in the healthy controls. The difference was statistically significant (p = 0.0005 for both). The persistence of this immature pattern was highly associated with UTI and VUR.

Ureteric jet in the anaesthetised child.

We have already suggested that there is an active bimodal sphincteric mechanism in the human vesicoureteral junction (VUJ). This mechanism is affected by immaturity, hormonal effects and surgical ablation. This study set out to investigate the effects of anaesthesia on this mechanism. A total of 16 children undergoing surgery were recruited. They were well hydrated. The ureteric jets before and after anaesthesia were recorded using the colour and pulse wave Doppler. Of the total, 14 children showed mature (complex pattern) and two showed immature (monophasic pattern) waveforms before surgery. After anaesthesia, all showed the monophasic waveform (p=0.01). Thus, the sphincteric action of VUJ as manifest by the complexity of the ureteric jet was modified by anaesthesia by loss of the complex pattern. This supports the hypothesis that the complex pattern is a neural modulation of the simpler myogenic mechanism that produces the monophasic jet.

Ureteric jet Doppler waveform and bladder wall thickness in children with nocturnal enuresis.

To test the hypothesis that the presence of nocturnal enuresis is related to increased frequency of immature vesicoureteric function, which is further associated with detrusor overactivity, we compared the incidence of immature monophasic ureteric jet in children with and without nocturnal enuresis. The relationship between monophasic ureteric jet Doppler wave form and bladder wall thickness was further explored in the enuresis group. Ultrasound examinations were performed in 511 children suffering from nocturnal enuresis and 266 normal controls. Doppler wave forms of the ureteric jet on each side and the bladder wall thickness after voiding were recorded. Standard urodynamic studies were obtained in 203 enuretic children for correlations with ultrasound findings. There was a significant increase in the incidence of monophasic ureteric jet waveforms in enuretic children when compared with the controls (19.2% versus 6.4% on the right side, 19.2% versus 8.3% on the left side, all p < 0.01). Furthermore, immature monophasic waveforms were more commonly seen in the enuretic group with markedly thickened bladder wall. Enuretic children with bilateral immature ureteric jet waveforms and markedly thickened bladder wall showed multiple significant urodynamic abnormalities (p < 0.05). The above observations could be accounted for by immaturity of both vesicoureteric junction and detrusor muscle.