Caucasian male infants and boys with hypospadias exhibit reduced anogenital distance.

BACKGROUND: Animal models of endocrine dysfunction have associated male genital defects with reduced anogenital distance (AGD). Human studies have correlated shorter AGD with exposure to putative endocrine disruptors in the environment but have not examined AGD in hypospadiac boys. We measured AGD in boys with hypospadias and those with normal genitals. METHODS: Data were collected prospectively on boys undergoing urologic procedures at the University of California San Francisco and the Children's Hospital of Oakland, CA, USA. Data included age, race, height, weight, BMI, urologic diagnoses and AGD. To minimize any potential effects of race on observed AGD, we examined only Caucasian boys. Differences between boys with hypospadias and those with normal genitals were examined through two-tailed Student's t-tests. RESULTS: One hundred and nineteen Caucasian boys ranging in age from 4 to 86 months underwent AGD measurement, of which 42 and 77 were boys with normal genitals and hypospadias, respectively. The mean (±SD) AGD of boys with hypospadias was 67 ± 1.2 versus 73 ± 1 mm for boys with normal genitals (P = 0.002). In these age-unmatched patient groups, there were also differences in age, height and weight (P = 0.0001, 0.0002 and 0.0004, respectively). After age matching (all <2 years of age), boys with hypospadias (n= 26) still featured a shorter AGD than boys with normal genitals (n= 26; 62 ± 2 versus 68 ± 2 mm respectively, P = 0.033) but the differences in age, height and weight were no longer significant. CONCLUSIONS: In humans, hypospadias may indeed be associated with reduced AGD. Additional studies are needed to corroborate these preliminary findings and to determine their etiology.

Complete androgen insensitivity syndrome: an anatomic evaluation and sexual function questionnaire pilot study.

PURPOSE: To further characterize the anatomy and sexual function of women with CAIS compared to normal females, and assess the utility of magnetic resonance imaging (MRI) to distinguish anatomical differences. MATERIALS AND METHODS: In a prospective cohort pilot study, five individuals with androgen insensitivity syndrome and six, normal, nulliparous women underwent an interview, physical examination, questionnaire completion and MRI of the pelvis. Statistical analysis was performed with emphasis on determining significant differences in anatomical findings and sexual satisfaction. RESULTS: MRI demonstrated statistically significant differences in vaginal depth and size that were not confirmed on physical exam. MRI and physical exam demonstrated a non-significant difference in average phallic thickness between the two groups, although the CAIS group clitoral width tended to be smaller. Physical exam demonstrated a higher average erect height and longer arm span in the CAIS patients but this was not statistically significant. No significant differences were noted in categories designed to assess satisfaction with ability to achieve orgasm, vaginal appearance and frequency of sexual intercourse between the two groups. CONCLUSIONS: The women with CAIS were as satisfied with sexual function as were the women within the control group. Physical exam and MRI did not find any statistically significant clinically relevant differences between the two groups.

Localized penile bullous pemphigoid of childhood.

Bullous pemphigoid is an acquired autoimmune bullous condition that is uncommon in childhood. Genital involvement is extremely rare. We present a case of a 7-year-old boy with bullous lesions confined to the glans penis. Precise diagnosis is based on clinical presentation and specific histopathologic testing. Oral corticosteroid therapy is the treatment of choice.

Hydrocele in the pediatric patient: inguinal or scrotal approach?

PURPOSE: The recommended approach for repairing hydrocele in children is inguinal to address a patent processus vaginalis. Hydrocele repair in adults is performed with a scrotal incision. We identified an age above which a significant percent of children had noncommunicating hydroceles, justifying a scrotal approach. MATERIALS AND METHODS: A retrospective chart review was performed of children undergoing hydrocele repair at our institution between 1998 and 2006. Operative reports were reviewed by 2 investigators and intraoperative findings were recorded for statistical analysis relating age and findings at the time of the procedure using logistic regression and ROC analysis. Laterality and recurrence rates were also noted. RESULTS: In this retrospective chart review 82.1% of hydroceles in children older than 10 years had intraoperative findings consistent with noncommunicating hydrocele and 86.4% in children older than 12 years were noncommunicating. One hydrocele in the age group older than 12 years was communicating and the history was suggestive of communication. Age was significantly associated with a patent processus vaginalis (OR 0.783, p <0.0001). CONCLUSIONS: It is possible in children older than 12 years to repair hydroceles through a scrotal incision unless the clinical history is suggestive of a communication. Children younger than 12 years should undergo inguinal exploration for hydrocele repair.

Decrease in glial glutamate transporter variants and excitatory amino acid receptor down-regulation in a murine model of ALS-PDC.

Glutamate transporter proteins appear crucial to controlling levels of glutamate in the central nervous system (CNS). Abnormal and/or decreased levels of various transporters have been observed in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) and in other neurological disorders. We have assessed glutamate transporter (GLT-1/EAAT2) levels in mice fed washed cycad flour containing a suspected neurotoxin that induces features resembling the Guamanian disorder, ALS-PDC. Down-regulation of glutamate transporter subtypes was detected by immunohistology using antibodies specific for two glial glutamate transporter splice variants (GLT-1alpha and GLT-1B). Immunohistology showed a "patchy" loss of antibody label with the patches centered on blood vessels. Computer densitometry showed significantly decreased GLT-1alpha levels in the spinal cord and primary somatosensory cortex of cycad-fed mice. GLT-1B levels were significantly decreased in the spinal cord, in the motor, somatosensory, and piriform cortices, and in the striatum. Western blots showed a 40% decrease in frontal motor cortex and lumbar spinal cord of cycad-fed mice that appeared to be phosphorylation-dependent. Receptor-binding assays showed decreased NMDA and AMPA receptor levels and increased GABAA receptor levels in cycad-fed mice cortex. These receptor data are consistent with an increased level of extracellular glutamate. The generalized decrease in GLT-1, decreased excitatory amino acid receptor levels, and increased GABAA receptor levels may reflect an early glutamate-mediated excitotoxicity following cycad exposure. Deciphering the series of events leading to neurodegeneration in cycad-fed animals may provide clues leading to therapeutic approaches to halt the early stages of disease progression.

Behavioral and neurological correlates of ALS-parkinsonism dementia complex in adult mice fed washed cycad flour.

Consumption of cycad seed products (Cycas circinalis) is one of the strongest epidemiological links to the Guamian neurological disorder amyotrophic lateral sclerosis-parkinsonism-dementia complex (ALS-PDC), however, the putative toxin which causes neurodegeneration has never been identified definitively. To reexamine this issue, 6-7-mo-old, male CD-1 mice were assessed for motor and cognitive behaviours during and following feeding with pellets made from washed cycad flour. Cycad-fed animals showed early evidence of progressive motor and cognitive dysfunctions. Neurodegeneration measured using TUNEL and caspase-3 labeling was found in neocortex, various hippocampal fields, substantia nigra, olfactory bulb, and spinal cord. In vitro studies using rat neocortex have identified toxic compounds in washed cycad flour that induce depolarizing field potentials and lead to release of lactate dehydrogenase (LDH), both blocked by AP5. High-performance liquid chromatography (HPLC)/mass spectrometry of cycad flour samples failed to show appreciable amounts of other known cycad toxins, cycasin, MAM, or BMAA; only trace amounts of BOAA were present. Isolation procedures employing these techniques identified the most toxic component as beta-sitosterol beta-D-glucoside (BSSG). The present data suggest that a neurotoxin, or a toxic metabolite, not previously identified in cycad, is able to gain access to central nervous system (CNS) resulting in neurodegeneration of specific neural populations and in motor and cognitive dysfunctions. These data are consistent with a number of major features of ALS-PDC in humans.