Timothy M. Phillips

Primary Caregivers of Children Affected by Disorders of Sex Development: Mental Health and Caregiver Characteristics in the Context of Genital Ambiguity and Genitoplasty

Purpose. To determine the relationship between having a child with a DSD including ambiguous external genitalia, as well as the decision of whether or not to have early genitoplasty for that child, on the mental health and parenting characteristics of caregivers. Materials and Methods. Caregivers were recruited from centers that specialize in DSD medicine and completed the Beck Depression Inventory 2nd Edition (BDI-2), Beck Anxiety Index (BAI), Parent Protection Scale (PPS), Child Vulnerability Scale (CVS) and Parenting Stress Index/Short Form (PSI/SF). Results and Conclusions. Sixty-eight caregivers provided informed consent and completed the study. Among female caregivers whose children never received genitoplasty, greater parenting stress was reported . For male caregivers, those whose children received genitoplasty within the first year of life reported more overprotective parenting and parenting stress than those whose children received genitoplasty later than 12 months of age ; , respectively).

Parenting Characteristics of Female Caregivers of Children Affected by Chronic Endocrine Conditions: A Comparison Between Disorders of Sex Development and Type 1 Diabetes Mellitus

Rearing a child with a chronic illness is stressful and can potentially affect parenting style, which may result in poorer outcomes for children. The purpose of this study was to compare parenting characteristics of female caregivers rearing children with a disorder of sex development (DSD) to female caregivers rearing children with type 1 diabetes mellitus (T1DM). Caregivers of both groups were matched according to age and compared on measures of stress and parenting practices. Both groups demonstrated significant levels of stress and negative parenting practices. Children with T1DM and male children with non-life-threatening DSD were perceived as more vulnerable by their caregivers. Better understanding of parenting experiences of female caregivers rearing children with DSD, particularly male children, will facilitate the development of individualized interventions to ameliorate negative parenting practices and stress, with the long-term goal of improved health outcomes for their children.

Molecular Effects of Genistein on Male Urethral Development

PURPOSE The increasing incidence of hypospadias is partly attributed to increased gestational exposure to endocrine disruptors. We investigated the effects of genistein, the primary phytoestrogen in soy, on the molecular program of male urethral development. MATERIALS AND METHODS Female mice were fed diets supplemented with genistein (500 mg/kg diet) or control diets before breeding and throughout gestation. Urethras from embryonic day 17.5 male fetuses were harvested, and RNA was prepared, amplified, labeled and hybridized on whole genome microarrays. Data were analyzed using packages from the R/Bioconductor project. Immunohistochemical analysis and immunoblotting were used to confirm the activity of MAPK and the presence of Ntrk1 and Ntrk2 during urethral development. RESULTS Gestational exposure to genistein altered the urethral expression of 277 genes (p <0.008). Among the most affected were hormonally regulated genes, including IGFBP-1, Kap and Rhox5. Differentially expressed genes were grouped into functional pathways of cell proliferation, adhesion, apoptosis and tube morphogenesis (p <0.0001), and were enriched for members of the MAPK (p <0.00001) and TGF-β (p <0.01) signaling cascades. Differentially expressed genes preferentially contained ELK1, Myc/Max, FOXO, HOX and ER control elements. The MAPK pathway was active, and its upstream genistein affected tyrosine kinase receptors Ntrk1 and Ntrk2 were present in the developing male urethra. CONCLUSIONS Gestational exposure to genistein contributes to hypospadias by altering pathways of tissue morphogenesis, cell proliferation and cell survival. In particular, genes in the MAPK and TGF-β signaling pathways and those controlled by FOXO, HOX and ER transcription factors are disrupted.

Evaluation of Pelvic Floor Muscular Redistribution After Primary Closure of Classic Bladder Exstrophy by 3-Dimensional Magnetic Resonance Imaging

PURPOSE We used 3-dimensional magnetic resonance imaging reconstruction to generate models of the pelvic floor musculature in classic bladder exstrophy, allowing for statistical analysis of changes seen in the anatomy after primary closure. MATERIALS AND METHODS Patients with classic bladder exstrophy underwent pelvic magnetic resonance imaging before and after primary closure. Contours of the levator ani were mapped and measured in 3-dimensional space. In addition, 2-dimensional angles and measurements were used to make a quantitative and qualitative analysis of the pelvic floor before and after closure. RESULTS A total of 19 cases of classic bladder exstrophy were included in the study, with 12 closed as newborns without osteotomy and 7 closed later with osteotomy. In both groups the pre-closure exstrophy pelvic floor in the axial plane was box-like and after closure it had a more inward rotation. The steepness and angulation of the levator ani muscle remained relatively unchanged in both groups. The levator ani muscle group, with and without osteotomy, was redistributed into the anterior compartment of the pelvis after closure. Postoperatively a successfully closed exstrophy had the bladder positioned deeply within the pelvis. After closure the levator ani muscle regained the expected smooth contoured shape. CONCLUSIONS Primary closure of bladder exstrophy 1) reshapes the pelvis from a box-like configuration to a more inwardly rotated hammock, 2) redistributes a significant portion of the levator ani muscle into the anterior compartment and 3) facilitates a smooth uniform contouring to the pelvic floor. Closing the bony pelvic ring by pubic reapproximation in the newborn or by osteotomy in an infant produces similar changes in the pelvic floor.

Degree of external genital malformation at birth in children with a disorder of sex development and subsequent caregiver distress.

PURPOSE We determined whether the degree of genital malformation at birth in children with a disorder of sex development is related to subsequent caregiver distress, specifically symptoms of depression and anxiety. MATERIALS AND METHODS A total of 66 caregivers of children with disorders of sex development were recruited from 3 centers that specialize in disorders of sex development medicine. The caregivers completed the Beck Depression Inventory, 2nd Edition and the Beck Anxiety Inventory. The childs Prader score at birth was determined by the childs treating pediatric endocrinologist and/or pediatric urologist at each institution. RESULTS Results from the current study revealed that for caregivers of male children, under masculinization of the childs genitals at birth was significantly related to higher levels of subsequent caregiver depression. In contrast, over masculinization of the genitals of female children at birth was unrelated to caregiver depression or anxiety. CONCLUSIONS These findings suggest that caregivers of male children with disorders of sex development may be at increased risk for psychological distress and could benefit from family based psychosocial interventions.

Primary closure of bladder exstrophy

• Interfragmentary pins, external fixator, and orthopaedic instruments (osteotomy, if required); • Supplies for Buck’s or Bryant’s traction (as needed); • 3and 5-F paediatric feeding tubes (ureteric stents); • 10 F Malecot drain (suprapubic tube); • 2–0 silk ties (umbilical vessels); • 3–0 and 5–0 polydioxanone sutures (bladder and urethral closure); • 3–0 nylon, 4–0 chromic, 3–0 polyglactin (secure drains); • No. 2 nylon sutures (intrapubic stitch); • Paediatric Van Buren sounds.

Urological outcomes in the omphalocele exstrophy imperforate anus spinal defects (OEIS) complex: Experience with 80 patients

OBJECTIVE To review the urological management and outcomes of patients with the OEIS (omphalocele, exstrophy of the bladder, imperforate anus, spinal abnormalities) complex. PATIENTS AND METHODS 80 patients with the OEIS complex managed at a single institution between 1974 and 2009 were reviewed. RESULTS 37 had initial closure at our institution (2 failed - 5%); 22 with successful closure were referred for incontinence; 15 failed closure at an outside institution (2 of whom are awaiting closure); 6 are skin-covered variants. Osteotomy was performed in 39/43 (91%) with successful closure versus 8/17 (47%) who failed initial bladder closure. 40 were dry (56%), but most needed additional urinary reconstruction: 2 had small bowel neobladders; 32 (84%) had augmentation cystoplasty; 30 (79%) had a continent catheterizable channel; only 9 (24%) were continent with an intact urethra. Bladder neck reconstruction allowed dryness in 7 (18%). 45 patients had XY genotype--19 had female gender assignment at birth. All patients with XX genotype had female gender assignment. CONCLUSIONS Osteotomy improves success of initial bladder closure. A bladder neck procedure, catheterizable channel, and augmentation cystoplasty will be required in the majority of patients to attain urinary dryness.

A Case Report of Dextranomer/Hyaluronic Acid Copolymer (DefluxTM) Implant Seen on CT as Distal Ureteral Calcification: How to Differentiate between Distal Ureteral Stones from DefluxTM?

Injection of dextranomer/hyaluronic acid copolymer (DefluxTM or Dx/HA) has become a common urologic procedure for treatment of low to intermediate grade vesicoureteral reflux. We report a rare case of a child with history of DefluxTM injection presenting to our emergency department with abdominal pain and non-contrast CT findings of a distal ureteral calcification mimicking a ureteral stone. Emergency physicians and consulting urologists need to be aware of this phenomenon and consider calcified Deflux as a potential differential diagnosis when evaluating young adults with abdominal pain and CT findings suggestive of distal ureteral calcification.

Operative management of pediatric urolithiasis

Surgical management of urinary stones in children remains challenging due to the smaller caliber of the urinary tract. Specific instruments have been designed to overcome some of the issues related to pediatric stone management. Endoscopic and percutaneous modalities for stone management have been shown to be as safe and effective in providing stone clearance in children as in adults. Technologies that have been shown to be safe in adults are being miniaturized for use in children. The current literature regarding pediatric urolithiasis was reviewed in an effort to identify trends in operative management. Additionally, techniques used successfully at our institution are described. Although not an exhaustive review of all available modalities and instruments, this review will provide an overview of the current techniques for the management of pediatric urolithiasis.