Pupillometric assessment of dysautonomia in pediatric bowel and bladder dysfunction: a pilot study.

Bowel and bladder dysfunction (BBD) refers to a heterogeneous group of voiding disorders, accounting for an estimated 40% of pediatric urology visits. Symptoms of BBD include enuresis, urgency, and urinary retention, often accompanied by constipation. The aim of this pilot study was to explore whether a pupillary response can be characterized for BBD, by examining the pupillary light reflex (PLR) before and after voiding among patients with BBD. A total of 28 patients aged from 7 to 21 years were recruited from the Wetting, Infections, and Stooling Help clinic at Children's National Medical Center. An infrared pupilometer was used to assess the PLR. Both baseline static and dynamic pupillometry assessments were obtained before and after voiding. Measurements were also taken after 5 min in the supine position, followed by 5 min standing to induce an orthostatic stressor. Visual inspection of the graphed data revealed a characteristic shape in 11 of 28 patients with voiding symptoms. In these 11 patients, the redilation arm of the PLR shows a 'notch,' or a brief reconstriction of the pupil before resting pupil size is reestablished (figure). This feature of the PLR has not been seen in previous and parallel studies using pupillometry to evaluate other populations. The results of this study suggest that a subset of patients with BBD may have a significant perturbation of autonomic regulation, identifiable through analysis of the PLR. To our knowledge, this 'notch' during redilation has not been previously described or seen in other patient populations and may represent a distinctive and readily identifiable physiologic marker of disease. These results are broadly aligned with results of other studies that have examined ANS activity in patients with BBD, although further study is needed to confirm the results of this pilot study and to assess relative contributions of sympathetic and parasympathetic function in producing pupillary abnormalities. This study has several limitations, including the small sample size, the absence of data on severity and duration of symptoms, and the absence of a control group of patients without any voiding symptoms. A simple tool for diagnosing BBD and for monitoring response to treatment could significantly improve the quality of treatment for one of the most common pediatric urologic complaints. Given the heterogeneity of symptoms under the BBD umbrella, pupillometric data could guide selection of treatment options, as well as assess adequacy of response to pharmacologic therapy.

Long-term nutritional consequences of bowel segment use for lower urinary tract reconstruction in pediatric patients.

OBJECTIVES: To identify whether nutritional abnormalities, specifically vitamin B12 deficiency, folate deficiency, and low carotene levels, are long-term sequelae of the use of ileum and/or colon for lower urinary tract reconstruction in pediatric patients. METHODS: Serum levels of vitamin B12, methyl malonic acid (MMA), carotene, and folate were measured 3 to 13 years (mean 6) after surgery in patients less than 18 years old at the time of operation. RESULTS: Thirteen (44.8%) of 29 patients had abnormal nutritional serum levels, with 5 (38.5%) of 13 having more than one abnormal value. Vitamin B12 was low in 4 (14%) of 29 patients; MMA was abnormally high in 7 (26%) of 27; and both folate and carotene levels were low in 4 (14.8%) of 27. No patient with reconstruction with colon alone (n = 3) had abnormal values, and no patient had any clinical signs or symptoms of vitamin B12 deficiency or fat malabsorption. CONCLUSIONS: Nutritional abnormalities can occur in patients after lower urinary tract reconstruction with ileum. No patient in this study had symptomatic abnormalities; however, long-term clinical effects may be significant. The implications of low folate levels in women of childbearing age must also be taken into consideration because of the potential association with congenital anomalies.

Sexually dimorphic expression of estrogen receptors, but not of androgen receptors in human fetal external genitalia.

Using immunohistochemistry, we investigated the distribution of androgen receptors (AR) and estrogen receptors (ER) in the external genitalia of human male and female fetuses at 18-22 weeks gestation. In the male, the corpus cavernosum, and the stroma of the inner prepuce, scrotum, and periphery of the glans were AR rich. The corpus spongiosum, a well defined structure that surrounds the penile urethra in the neonate, was not yet developed at this fetal age, but the periurethral mesenchyme (presumably the primordium of the corpus spongiosum) was intensely AR positive. In contrast, the epithelium of the preputial skin, penile shaft skin, and scrotal skin were AR negative. The urethral plate in the distal glans was nonpatent and was filled with a meshwork of AR-negative epithelial cells. Canalization of the AR-negative urethral plate was observed to begin where it joined the patent distal penile urethra, which was AR positive. Male external genitalia lacked ER, ruling out a direct influence of maternal estrogen on male genital development. Interestingly, female external genital structures contained AR, and the distribution of AR and staining intensity were strikingly similar to that in the male. The distribution of AR in the female provides a mechanism to explain how female external genitalia become masculinized if exposed to elevated androgen levels in the first trimester. Moreover, it implies that in the male, these AR indeed mediate androgen-dependent male external genital development. Female fetal external genitalia were also intensely ER positive in the stroma of the labia minora and in the periphery of the glans and inner prepuce. The presence of ER suggests that maternal estrogen may play a direct role in female external genital development, challenging the widely held view that female external genital development is passive because it can occur in the absence of fetal gonadal hormones.