ABSTRACT
OBJECTIVE: Illness intrusiveness refers to the subjective cognitive appraisal of a chronic health condition interfering in daily, valued activities and may be highly relevant for parents of children with atypical genital appearance due to differences of sex development (DSD). However, a measure of illness intrusiveness has not been validated for this population. The current study aimed to evaluate the factor structure of the Illness Intrusiveness Scale for Parents (IIS-P) and examine convergent validity. METHODS: Participants included 102 parents (Mage = 33.39 years, SD = 6.48; 58% mothers) of 65 children (<2 years old) diagnosed with DSD participating in a larger, longitudinal study. Parents completed the IIS-P as well as self-report measures of stigma, and anxious and depressive symptoms. An exploratory factor analysis (EFA) was conducted. RESULTS: EFA results supported a 1-factor intrusiveness solution (α = .93), as well as a 2-factor solution measuring intrusiveness on daily living (α = .92) and community connectedness (α = .85). The 1-factor solution and both factors of the 2-factor solution demonstrated significant convergent validity with stigma as well as anxious and depressive symptoms. CONCLUSIONS: Support emerged for both 1- and 2-factor solutions of the IIS-P in parents of children with DSD. The decision to evaluate illness intrusiveness as a total score or to examine the subscales of daily living and community connectedness should be tailored to the unique aims of researchers and clinicians. Future research should conduct a confirmatory factor analysis with both 1- and 2-factor models with larger, more diverse samples of caregivers.
Subject(s)
Disorders of Sex Development , Parents , Humans , Male , Female , Parents/psychology , Adult , Factor Analysis, Statistical , Disorders of Sex Development/psychology , Longitudinal Studies , Social Stigma , Depression/psychology , Psychometrics , Anxiety/psychology , Child, Preschool , Infant , Reproducibility of ResultsABSTRACT
OBJECTIVE: Differences of sex development (DSD) are congenital conditions in which individuals are discordant in their chromosomal, phenotypic, and/or gonadal sex. Treatment of DSD can involve surgical intervention to external genitalia to make anatomy seem male-typical (i.e., male genitoplasty). Caregiver-perceived decisional regret regarding young boys with DSD was explored quantitatively and qualitatively. METHOD: Participants (N = 39) were caregivers of infants (N = 23) diagnosed with DSD (mean age = 8.9 months, standard deviation = 5.9 months) reared male participating in a longitudinal investigation of psychosocial outcomes. Qualitative data were collected at 6 to 12 months after baseline enrollment to evaluate caregiver decision-making corresponding to levels of regret concerning their child's treatment. All but one infant received genital surgery before caregiver reporting on their decisional regret. Quantitative exploratory analyses evaluated longitudinal predictors of decisional regret at 6 to 12 months. RESULTS: When completing a write-in item inquiring about decision-making and potential regret, most caregivers (n = 16, 76%) reported that their child's genital surgery was their first medical decision. Two caregivers referenced gender assignment as a decision point. One-third of caregivers reported some level of decisional regret (33%), with 67% reporting no regret. No hypothesized predictors of decisional regret were statistically significant. CONCLUSION: Many caregivers of infants with DSD reared male view genital surgery as a first health care decision. Approximately one-third of caregivers reported some level of decisional regret. Further research is warranted to explore long-term decisional regret; it will be particularly important to investigate the decisional regret of patients with DSD.
Subject(s)
Caregivers , Decision Making , Child , Humans , Male , Infant , Caregivers/psychology , Emotions , Sexual DevelopmentABSTRACT
OBJECTIVE: Illness uncertainty is a salient experience for caregivers of children with disorders/differences of sex development (DSD) presenting with ambiguous genitalia; however, no validated measure of illness uncertainty exists for this unique population. Thus, the current study aimed to preliminarily identify the factor structure of the Parental Perception of Uncertainty Scale (PPUS) in caregivers of children with DSD presenting with ambiguous genitalia and examine the convergent validity of the PPUS. METHODS: Participants included 115 caregivers (Mage = 32.12 years, SD = 6.54; 57% mothers) of children (<2-year-olds) diagnosed with DSD participating in a larger, longitudinal study. Caregivers completed the PPUS as well as self-report measures of anxious, depressive, and posttraumatic stress symptoms. An exploratory factor analysis was conducted. RESULTS: Exploratory factor analysis results indicated that a 23-item 1-factor solution was the most parsimonious and theoretically sound factor structure (α = 0.92). Convergent validity analyses demonstrated further support for the use of the 23-item 1-factor solution over the original PPUS factor structure. CONCLUSION: These results demonstrate the preliminary clinical and research utility of the PPUS with caregivers of children with DSD presenting with ambiguous genitalia. The PPUS may benefit from further refinement through qualitative research and item adaptation to capture uncertainties unique to DSD presenting with ambiguous genitalia. In addition, future research should replicate the proposed factor structure using confirmatory factor analysis with a separate, larger sample of caregivers of children with DSD to confirm the factor structure.
Subject(s)
Disorders of Sex Development , Female , Humans , Child , Child, Preschool , Uncertainty , Longitudinal Studies , Disorders of Sex Development/diagnosis , Anxiety/diagnosis , ParentsABSTRACT
INTRODUCTION: Caregivers of female infants with congenital adrenal hyperplasia (CAH) often confront complex medical decision-making (e.g., early feminizing genitoplasty). OBJECTIVE: This study aimed to evaluate the relevant medical decisions and subsequent decisional regret of caregivers following their child's genitoplasty. STUDY DESIGN: Caregivers (N = 55) were recruited from multidisciplinary treatment programs for participation in a longitudinal study. Qualitative data was collected at 6-12 months following feminizing genitoplasty to evaluate caregiver-reported decision points across their child's treatment. Quantitative exploratory analysis evaluated pre-operative predictors of subsequent decisional regret. DISCUSSION: When prompted about their decision-making and potential regret, most caregivers (n = 32, 80%) reported that their daughter's genital surgery was their primary medical decision. Specific themes regarding genital surgery included the timing and type of surgery. Most caregivers reported no decisional regret (62%), with 38% reporting some level of regret. Greater pre-operative illness uncertainty predicted heightened decisional regret at follow-up, p = .001. CONCLUSION: Two-thirds of caregivers of female infants with CAH reported not regretting their decision-making. Nevertheless, over one-third of caregivers reported some level of regret, suggesting the need for improvements in shared decision-making processes. Many, but not all, families reported that this regret was related to surgical decision-making. Reducing caregiver illness uncertainty (e.g., providing clear information to families) may increase their satisfaction with decision-making. Further research is needed to determine how the evolving care practices surrounding early genitoplasty will impact families.
Subject(s)
Adrenal Hyperplasia, Congenital , Caregivers , Adrenal Hyperplasia, Congenital/surgery , Decision Making , Emotions , Female , Humans , Infant , Longitudinal StudiesABSTRACT
INTRODUCTION: Differences of sex development (DSD) are congenital conditions in which there is atypical chromosomal, gonadal and/or phenotypic sex. A phenotype of severe genital atypia in patients raised as male is a relatively rare occurrence and standards for management are lacking. Decision making for early surgical planning in these rare cases includes, but is not limited to, degree of atypia, location of testes, and presence of MÏllerian remnants. In this study we describe surgical approaches and short-term outcomes for masculinizing genitoplasty in moderate to severe genital atypia in young patients raised male, for whom parents opted for early surgery. METHODS: This NIH-sponsored study is an ongoing, observational, multicenter investigation assessing medical, surgical and psychological outcomes in children and their parents affected by atypical genitalia due to DSD. Participants were prospectively enrolled from 12 children's hospitals across the United States that specialize in DSD care. Criteria for child enrollment were a Quigley score of 3-6 in those with a 46, XY or 45,X/46, XY chromosome complement, age <3 years with no previous genitoplasty; patients were included independent of whether genitoplasty was performed. Cosmesis was graded according to a 4-point Likert scale and complications per the Clavian-Dindo classification. RESULTS: Of the 31 participants, 30 underwent hypospadias repair and 1 patient did not undergo a genitoplasty procedure. The majority of participants (22) received a staged hypospadias repair. Seventeen complications were identified in 12 of the 31 children (41%) at 12 months of follow up. Glans dehiscence and urethrocutaneous fistula were the most common complications. Orchiopexy was performed in 14 (44%) and streak gonads were removed in 4 (13%) participants. Both parents and surgeons reported improved cosmesis after surgery when compared to baseline. CONCLUSION: Genitoplasty was chosen by parents for the majority of children eligible for study. No single surgical approach for masculinizing moderate to severe genital ambiguity in young patients with 46, XY or 45,X/46, XY DSD was adopted by all surgeons. Complications occurred in 41% of those who underwent genitoplasty for severe hypospadias. Overall, appearance of the genitals, as determined by parents and surgeons, improved following genitoplasty. Outcomes of early genitoplasty are needed to guide families when making decisions about such procedures for their young children.
Subject(s)
Disorders of Sex Development , Plastic Surgery Procedures , Child , Child, Preschool , Disorders of Sex Development/surgery , Female , Genitalia/surgery , Humans , Male , Prospective Studies , Sexual DevelopmentABSTRACT
OBJECTIVE: This study identifies trajectories of parent depressive symptoms after having a child born with genital atypia due to a disorder/difference of sex development (DSD) or congenital adrenal hyperplasia (CAH) and across the first year postgenitoplasty (for parents who opted for surgery) or postbaseline (for parents who elected against surgery for their child). Hypotheses for four trajectory classes were guided by parent distress patterns previously identified among other medical conditions. METHODS: Participants included 70 mothers and 50 fathers of 71 children diagnosed with a DSD or CAH with reported moderate to high genital atypia. Parents were recruited from 11 US DSD specialty clinics within 2 years of the child's birth and prior to genitoplasty. A growth mixture model (GMM) was conducted to identify classes of parent depressive symptoms over time. RESULTS: The best fitting model was a five-class linear GMM with freely estimated intercept variance. The classes identified were termed "Resilient," "Recovery," "Chronic," "Escalating," and "Elevated Partial Recovery." Four classes have previously been identified for other pediatric illnesses; however, a fifth class was also identified. The majority of parents were classified in the "Resilient" class (67.6%). CONCLUSIONS: This study provides new knowledge about the trajectories of depressive symptoms for parents of children with DSD. Future studies are needed to identify developmental, medical, or familial predictors of these trajectories.
Subject(s)
Adrenal Hyperplasia, Congenital , Parents , Child , Genitalia , HumansABSTRACT
Stigma is a salient experience for both caregivers/parents and individuals with Disorders/Differences of Sex Development (DSD) as evidenced through qualitative and preliminary quantitative reports. However, few validated measures of associative stigma (i.e., vicarious stigma experienced through close association with someone who is socially stigmatized) for parents of children with DSD exist. The present study aims to (1) determine the factor structure of the adapted Stigma Scale - Parent, and (2) examine convergent validity of the factor structure with measures of parent psychosocial adjustment. Confirmatory factor analytic results revealed two factors: a parent-focused factor and a child-focused factor. The parent-focused factor demonstrated convergent validity with parent adjustment measures, but the child-focused factor did not. Together, these results indicate that parent-focused and child-focused stigma are distinct factors, with parent-focused associative stigma being related to parent adjustment following DSD diagnosis. Future research should further refine this measure to determine predictive validity and clinical value.
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PURPOSE OF REVIEW: To review the presentation, natural history and treatment of renal cell carcinoma in children and young adults with renal cell carcinoma (RCC). RECENT FINDINGS: Complete resection of lymph nodes at the time of tumor resection can improve clinical outcomes and limit the need for adjuvant chemotherapy. Genetic alterations that lead to translocation tumors are a therapeutic target of receptor tyrosine kinase inhibitors. SUMMARY: The incidence of RCC increases with age. Unlike adult patients, young patients with RCC present symptomatically and at higher stage and grade. Translocation tumors predominate RCC in children with biologic activity characterized by early spread to lymph nodes with small primary tumors. Preoperative imaging is poorly sensitive for positive lymph nodes; as such, surgeons should have a low threshold for lymph node sampling during tumor resection. Despite the advanced stage at presentation, the prognosis in children is more favorable than their adult counterparts. Complete resection of lymph nodes at the time of surgical resection improves patient prognosis. Chemotherapy targeting the PI3/AKT pathway has demonstrated clinical benefit.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/therapy , Kidney Neoplasms/diagnosis , Kidney Neoplasms/therapy , Antineoplastic Agents/therapeutic use , Chemotherapy, Adjuvant , Child , Humans , Immunotherapy , Lymph Node Excision , Nephrectomy/methods , Prognosis , Young AdultABSTRACT
Parents of children with disorders of sex development (DSD) report significant psychological distress, including posttraumatic stress symptoms (PTSS), with mothers consistently reporting higher rates of psychological distress than fathers. However, psychological factors contributing to PTSS in both parents are not well understood. The present study sought to fill this gap in knowledge by examining PTSS and illness uncertainty, a known predictor of psychological distress, in parents of children recently diagnosed with DSD. Participants were 52 mothers (Mage = 32.55 years, SD = 5.08) and 41 fathers (Mage = 35.53 years, SD = 6.78) of 53 infants (Mage = 9.09 months, SD = 6.19) with DSD and associated atypical genital development. Participants were recruited as part of a larger, multisite study assessing parents' psychosocial response to their child's diagnosis of DSD. Parents completed measures of illness uncertainty and PTSS. Mothers reported significantly greater levels of PTSS, but not illness uncertainty, than fathers, and were more likely than fathers to report clinical levels of PTSS (21.2% compared to 7.3%). Hierarchical regression revealed that parent sex, undiagnosed or unclassified DSD status, and illness uncertainty were each associated with PTSS. The overall model accounted for 23.5% of the variance associated with PTSS. Interventions targeting illness uncertainty may be beneficial for parents of children with newly diagnosed DSD.
Subject(s)
Disorders of Sex Development/psychology , Stress Disorders, Post-Traumatic/diagnosis , Uncertainty , Adult , Female , Humans , Infant , Male , Parent-Child RelationsABSTRACT
PURPOSE: Little is known about the phenotypes, diagnoses, and sex of rearing of infants with atypical genital development in the United States. As part of a multicenter study of these infants, we have provided a baseline report from US difference/disorder of sex development clinics describing the diagnoses, anatomic features, and sex of rearing. We also determined whether consensus guidelines are followed for sex designation in the United States. METHODS: Eligible participants had moderate-to-severe genital atypia, were aged <3 years, and had not undergone previous genitoplasty. Karyotype, genetic diagnosis, difference/disorder of sex development etiology, family history, and sex of rearing were collected. Standardized examinations were performed. RESULTS: Of 92 subjects, the karyotypes were 46,XX for 57%, 46,XY for 34%, and sex chromosome abnormality for 9%. The median age at the baseline evaluation was 8.8 months. Most 46,XX subjects (91%) had congenital adrenal hyperplasia (CAH) and most 46,XY subjects (65%) did not have a known diagnosis. Two individuals with CAH underwent a change in sex of rearing from male to female within 2 weeks of birth. The presence of a uterus and shorter phallic length were associated with female sex of rearing. The most common karyotype and diagnosis was 46,XX with CAH, followed by 46,XY with an unknown diagnosis. Phenotypically, atypical genitalia have been most commonly characterized by abnormal labioscrotal tissue, phallic length, and urethral meatus location. CONCLUSIONS: An increased phallic length was positively associated with rearing male. Among the US centers studied, sex designation followed the Consensus Statement recommendations. Further study is needed to determine whether this results in patient satisfaction.
Subject(s)
Adrenal Hyperplasia, Congenital/surgery , Disorders of Sex Development/genetics , Disorders of Sex Development/surgery , Plastic Surgery Procedures/legislation & jurisprudence , 46, XX Disorders of Sex Development/diagnosis , 46, XX Disorders of Sex Development/surgery , 46, XX Testicular Disorders of Sex Development/diagnosis , 46, XX Testicular Disorders of Sex Development/genetics , 46, XX Testicular Disorders of Sex Development/surgery , Adrenal Hyperplasia, Congenital/diagnosis , California , Disorders of Sex Development/diagnosis , Female , Health Policy/legislation & jurisprudence , Humans , Infant , Infant, Newborn , Male , Policy Making , Risk Assessment , Time FactorsABSTRACT
BACKGROUND/AIMS: Parents of children born with disorders of sex development (DSD) often experience anxiety, but risk factors, including parental perception of the severity of their child's DSD, have not been examined. We hypothesized that severity of illness (SOI) ratings would relate to parental anxiety, and would be higher for parents of children with a potentially life-threatening DSD (e.g., 21-hydroxylase deficiency). METHODS: Eighty-nine parents (Mage = 33.0, 56.2% mothers) of 51 children (Mage in months = 8.7) with a DSD including ambiguous genitalia were recruited from 12 specialized DSD clinics. Parents completed questionnaires prior to genitoplasty, 6 months post-genitoplasty, and 12 months post-genitoplasty (if completed). Data were analyzed with linear mixed modeling. RESULTS: Parental anxiety decreased over time, χ2(1) = 10.14, p < 0.01. A positive relationship between SOI and anxiety was found, with SOI being a strong predictor of anxiety (b = 0.53, p < 0.01; χ2[1] = 5.33, p < 0.05). An SOI by time interaction indicated SOI had an increasing effect on anxiety over time, b = 0.06, p < 0.05; χ2(1) = 6.30, p < 0.05. There was no diagnosis by SOI interaction. CONCLUSION: Parental anxiety decreased over time, but those with higher SOI ratings reported greater initial anxiety followed by slower resolution over time. Underlying etiology of DSD had no effect on the relationship between SOI and anxiety.
Subject(s)
Anxiety/psychology , Caregivers/psychology , Disorders of Sex Development/diagnosis , Parents/psychology , Perception , Adult , Female , Humans , Male , Quality of Life , Risk Factors , Severity of Illness Index , Surveys and QuestionnairesABSTRACT
Renal obstruction is frequently found in adults and children. Mechanical stimuli, including pressure and stretch in the obstructed kidney, contribute to damage; animal models of obstruction are characterized by increased cellular proliferation. We were interested in the direct effects of pressure and stretch on renal tubular cell proliferation. Human HKC-8 or rat NRK-52E proximal tubule cells were subjected to either pressure [0, 60 or 90 mmHg] or static stretch [0 or 20%] for 24 or 48 h. Cell proliferation was measured by cell counting, cell cycle analyzed by flow cytometry, and PCNA and Skp2 expression were determined by qPCR or western blot. Blood gases were determined in an iSTAT system. Proliferation was also assessed in vivo after 24 h of ureteral obstruction. There was a significant increase in HKC-8 cell number after 48 h of exposure to either 60 or 90 mmHg pressure. Western blot and qPCR confirmed increased expression of PCNA and Skp2 in pressurized cells. Cell cycle measurements demonstrated an increase in HKC-8 in S phase. Mechanical stretching increased PCNA protein expression in HKC-8 cells after 48 h while no effect was observed on Skp2 and cell cycle measurements. Increased PCNA expression was found at 24 h after ureteral obstruction. We demonstrate direct transduction of pressure into a proliferative response in HKC-8 and NRK-52E cells, measured by cell number, PCNA and Skp2 expression and increase in cells in S phase, whereas stretch had a less robust effect on proliferation.
Subject(s)
Cell Proliferation , Kidney Tubules, Proximal/cytology , Pressure , Animals , Cell Line , Humans , Kidney Tubules, Proximal/metabolism , Kidney Tubules, Proximal/physiology , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , Rats , Rats, Sprague-Dawley , S-Phase Kinase-Associated Proteins/genetics , S-Phase Kinase-Associated Proteins/metabolism , Stress, MechanicalABSTRACT
Mutations of CYP21A2 variably decrease 21-hydroxylase activity and result in a spectrum of disease expressions in patients with congenital adrenal hyperplasia (CAH). We examined the association between CYP21A2 mutations and virilization (Prader score) in females with CAH. The study population included 187 CAH females with fully characterized CYP21A2 mutations. One hundred fifty-eight patients were sorted into groups by expected enzyme activity (percent of normal activity) of the less severely affected allele: (A) null, 0%; (B) I2G, 1%; (C) I172N, 2%; and (D) V281L, >2%. We observed an inverse relationship between virilization and residual enzyme activity (P < 0.001). Subjects in group A or B had a significantly higher likelihood (unadjusted odds ratio: 16; P < 0.001) of developing severe virilization compared with those in group C. Surprisingly, 24% of group D patients, whose mutation is usually associated with nonclassical (NC) CAH, had severe virilization. Among subjects with the NC P30L mutation, 66% expressed unexpected virilization. Virilization, usually leading to extensive reconstructive surgery, is highly likely in patients with null or I2G mutations; however, NC mutations (P30L/V281L) may also lead to unexpected virilization. These findings have implications for prenatal counseling and highlight the need for additional investigations into other factors that influence virilization in CAH.
Subject(s)
Adrenal Hyperplasia, Congenital/genetics , Virilism/genetics , Female , Genotype , Humans , Mutation/genetics , PhenotypeABSTRACT
Surgical management of classical congenital adrenal hyperplasia (CAH) in 46, XX females has evolved significantly. Virilization of the genitalia of 46, XX females with CAH begins prenatally as a result of excess fetal androgen production. Improved understanding of anatomy and surgical outcomes has driven changes in surgical techniques as well as the timing of surgery. For endocrinologists treating these patients, it is important to understand the outcome of genitoplasty, identify patients who need further treatment and direct these patients to experienced surgeons. We performed a literature search on PubMed of publications addressing CAH and genital reconstruction published in the English language from 1990 to the present. In accordance with our institutional review board, we performed a retrospective analysis of clitoroplasty and/or vaginoplasty procedures performed by a single surgeon at our institution from 1996 to 2015. We found that genital reconstruction in 46, XX CAH patients is associated with few immediate post-operative, infectious, and urinary complications. Vaginal stenosis is a common complication of vaginal reconstruction and requires evaluation by an experienced surgeon. Clitoral pain or decreased sensation can be associated with clitoral recession and clitorectomy. Outcomes in sexual satisfaction and gender identity can also be impacted by surgical technique and success. Long term follow up and patient reported feedback are crucial to our understanding and management of this special group of patients. Improved awareness and understanding of the complications of genital surgery will allow endocrinologists to know what to ask patients and be ready to provide them with a resource with the understanding and experience to help them improve their quality of life.
Subject(s)
Adrenal Hyperplasia, Congenital/surgery , Endocrinology/methods , Gynecologic Surgical Procedures/methods , Plastic Surgery Procedures/methods , Child , Child, Preschool , Chromosomes, Human, X , Clitoris/surgery , Constriction, Pathologic , Female , Follow-Up Studies , Humans , Patient Satisfaction , Quality of Life , Retrospective Studies , Vagina/pathology , Virilism/surgery , Vulva/surgeryABSTRACT
BACKGROUND: Feminizing genitoplasty techniques have diversified to encompass the spectrum of atypical genitalia in 46,XX congenital adrenal hyperplasia (CAH) patients. However, long-term outcomes evaluating postoperative continence following complex vaginoplasty remain scarce. OBJECTIVE: The aim was to review our surgical experience and assess postoperative urinary continence outcomes in CAH patients following complex, primary vaginoplasty. STUDY DESIGN: We retrospectively reviewed CAH patients who underwent complex, primary vaginoplasty at a single center by a single surgeon from 1996 to 2013. We collected data on clinical characteristics, surgical techniques and postoperative urinary continence outcomes. In patients who had reached toilet-training age, continence outcomes were reviewed. RESULTS: Twenty-four patients met the inclusion criteria. The median age at the time of surgery was 8 months (interquartile range [IQR] 1 year-6 months). The median length of follow up was 6 years (IQR 10 years-3 years). These patients required complex reconstruction because of more extensive virilization: total urogenital mobilization (TUM, 10), pull-through vaginoplasty (9), partial urogenital mobilization (3), or pull-through vaginoplasty with partial urogenital mobilization (2). After surgery, 15 out of 24 (62.5%) reported age appropriate toilet-training without further complaints. Seven (29.2%) patients reported daytime incontinence or enuresis that resolved with conservative management. Two patients reported day and night incontinence requiring urethral bulking procedures following TUM. DISCUSSION: Twenty-two (91.7%) of our patients achieved continence without further surgical intervention. Of these patients, the TUM patients had serious incontinence issues. Our study represents a review of clinically significant cases from the female CAH population. The limitations of our study include a relatively small sample size and retrospective design. CONCLUSION: Females with CAH and urogenital virilization most often achieved age appropriate toilet-training following vaginoplasty. Daytime incontinence and enuresis resolved without operative management in the vast majority of cases. TUM carries a risk of severe incontinence and may require further procedures to achieve urinary continence.
Subject(s)
Adrenal Hyperplasia, Congenital/surgery , Gynecologic Surgical Procedures/methods , Plastic Surgery Procedures/methods , Urinary Incontinence/physiopathology , Urodynamics/physiology , Vagina/surgery , Adrenal Hyperplasia, Congenital/complications , Adrenal Hyperplasia, Congenital/physiopathology , Female , Follow-Up Studies , Humans , Infant , Postoperative Period , Retrospective Studies , Time Factors , Treatment Outcome , Urinary Incontinence/etiologyABSTRACT
PURPOSE: In the past many female patients with congenital adrenal hyperplasia and atypical genitalia were surgically treated with clitoral recession or incomplete reduction of erectile bodies. We report the results of repeat clitoral surgery performed for clitoral pain or enlargement using a nerve sparing reduction clitoroplasty technique. MATERIALS AND METHODS: We identified 6 female patients with congenital adrenal hyperplasia who had undergone prior clitoral recession or incomplete reduction elsewhere. They then presented to our center with clitoral pain or enlargement, where they were treated with nerve sparing clitoroplasty between 2000 and 2010. We collected patient reported data relating to clitoral sensation and sexual function outcomes. RESULTS: Mean ± SD age at evaluation for repeat clitoral surgery was 21 ± 7 years and mean age at clitoroplasty was 22 ± 8 years. Median postoperative followup was 9 months (IQR 32-6). All patients showed improvement with resolution of clitoral pain or enlargement. CONCLUSIONS: Clitoral pain and enlargement upon arousal can be a major concern for women with clitoromegaly and congenital adrenal hyperplasia after clitoral recession is performed. Our series suggests that clitoral recession or incomplete reduction in childhood may be an inadequate initial solution in the congenital adrenal hyperplasia population due to the potential for future androgen elevation and the possibility of later symptom development. In addition we found that patients may be successfully treated with nerve sparing clitoroplasty, resulting in resolution of pain and ability to engage in sexual activity.
Subject(s)
Adrenal Hyperplasia, Congenital/surgery , Clitoris/innervation , Clitoris/surgery , Genital Diseases, Female/surgery , Pain/surgery , Postoperative Complications/surgery , Adolescent , Adult , Child , Female , Gynecologic Surgical Procedures/methods , Humans , Organ Sparing Treatments , Retrospective Studies , Young AdultABSTRACT
Chloride intracellular channel 4 (CLIC4) is a mammalian homologue of EXC-4 whose mutation is associated with cystic excretory canals in nematodes. Here we show that CLIC4-null mouse embryos exhibit impaired renal tubulogenesis. In both developing and developed kidneys, CLIC4 is specifically enriched in the proximal tubule epithelial cells, in which CLIC4 is important for luminal delivery, microvillus morphogenesis, and endolysosomal biogenesis. Adult CLIC4-null proximal tubules display aberrant dilation. In MDCK 3D cultures, CLIC4 is expressed on early endosome, recycling endosome and apical transport carriers before reaching its steady-state apical membrane localization in mature lumen. CLIC4 suppression causes impaired apical vesicle coalescence and central lumen formation, a phenotype that can be rescued by Rab8 and Cdc42. Furthermore, we show that retromer- and branched actin-mediated trafficking on early endosome regulates apical delivery during early luminogenesis. CLIC4 selectively modulates retromer-mediated apical transport by negatively regulating the formation of branched actin on early endosomes.
Subject(s)
Actins/metabolism , Chloride Channels/metabolism , Mitochondrial Proteins/metabolism , Animals , Chloride Channels/genetics , Dogs , Endosomes/metabolism , Exocytosis/genetics , Exocytosis/physiology , Immunoprecipitation , Madin Darby Canine Kidney Cells , Mice , Mice, Knockout , Mitochondrial Proteins/genetics , Protein Transport/genetics , Protein Transport/physiologyABSTRACT
BACKGROUND: As the benefits of patient-centered care have become more widely recognized, it is important to understand patients' sentiments regarding aspects affecting their care. In an effort to display more sensitivity to patient concerns, the term "disorders of sex development" (DSD) was proposed in 2006 as new nomenclature to replace older terms that were considered to have negative connotations. METHODS: The objective of the study was to examine the views of congenital adrenal hyperplasia (CAH) patients and their caregivers regarding the new nomenclature. The study was observational to evaluate the views of the CAH community, and the primary endpoint was perception of the term DSD. The study was conducted as a survey about views regarding DSD nomenclature. The survey was sent via email to eligible subjects. Along with a short introduction explaining the term DSD, the survey was sent to eligible CAH patients and their caregivers. 589 CAH patients or family members participated in the survey. RESULTS: A total of 589 responses were received (255 classical females, 104 non-classical females, 174 males, 56 not specified) (547 U.S., 42 international) (128 CAH patients, 408 parents or other family members). 70.6% had never heard the term DSD. 71.0% disliked or strongly disliked the term DSD. 83.6% stated they did not identify with the term DSD. 76.0% felt that the term DSD has a negative effect on the CAH community. There was no significant difference in opinion of DSD between classical females and other CAH patients, between US and international, between surgical and non-surgical patients, or between patients and parents. There was no correlation with patient age. CONCLUSIONS: Our results indicate that the majority of parents and patients with CAH are dissatisfied with the term DSD. Our results highlight the challenges within the field of DSD to reach a consensus regarding a sensitive topic and to bridge the gap between current medical practice and patient satisfaction. It is the authors' belief that reconsideration of the current nomenclature and ongoing dialogue between the medical community and patients will eventually lead to removal of stigmatization, better management protocols, and improved outcomes.
ABSTRACT
We established a human tissue explant model to facilitate study of cutaneous squamous cell carcinoma. We accomplished this by implanting debulked SCC, from surgical discard, into nude rats. Human SCC remained viable and continued to proliferate for at least 4 weeks and showed evidence of neovascularization. At 4 weeks, SCC implants showed a trend toward increased PCNA positive cells compared to fresh SCC cells/mm(2) tissue) supporting continued proliferation throughout engraftment. Von Willebrand's Factor (VWF) positive cells were found within implants and likely represented rat vessel neovascularization. Human Langerhans' (Langerin+) cells, but no T cells (CD3+, CD8+, FoxP3+), macrophages (CD163), or NK cells (NKp46), were present in SCC implants at 4 weeks. These findings support the possibility that LCs fail to migrate from cutaneous SCC and thus contribute to lack of effective antitumor response. Our findings also provide a novel model system for further study of primary cutaneous SCC.