Surgical Outcomes of Clitoroplasty in Children with Congenital Adrenal Hyperplasia and Clitoral Hypertrophy: A 19-Year Experience of a Single Surgeon.

This study aimed to describe the experience with clitoroplasty for clitoral hypertrophy in patients with congenital adrenal hyperplasia of a single surgeon. The medical records of female pediatric patients with congenital adrenal hyperplasia who underwent clitoroplasty at a tertiary referral hospital between 2002 and 2020 were retrospectively analyzed. Three different surgical techniques were applied for clitoroplasty: recession without reduction, reduction and recession, and girth reduction and recession. A total of 104 patients underwent clitoroplasty for clitoral hypertrophy. The median patient age at the time of surgery was 10 months (range, 4 months to 10 years). The operation time was longer in reduction clitoroplasty than in recession clitoroplasty without reduction (median, 153 vs. 111 min, p = 0.003). The mean postoperative pain score of the patients did not differ among the different clitoroplasty techniques. During the mean follow-up of 37.7 months, nine (8.6%) patients underwent reperformed clitoroplasty. The rate of reperformed operation was significantly higher in patients who underwent reduction clitoroplasty (17.3%) than in those who underwent recession without reduction (2%) or girth reduction and recession (0%) (p = 0.031). Early clitoroplasty in patients with congenital adrenal hyperplasia yielded good mid-term surgical outcomes in terms of cosmesis and recurrence rate, with minimal perioperative complications.

Validity and reliability of a home-based, guardian-conducted video voiding test for voiding evaluation after hypospadias surgery.

Purpose: To investigate the validity and reliability of a home-based, guardian-conducted video voiding test for assessing postoperative voiding function after hypospadias surgery. Materials and Methods: In a single center, patients who had undergone urethroplasty by a single surgeon and postoperative uroflowmetry and video voiding tests conducted between 2008 and 2016 were retrospectively reviewed. Urinary stream was categorized into five grades by three pediatric urologists in a blinded manner. The primary outcome was statistical correlation across raters as measured by Spearman correlation coefficient to validate the interpretation of the video voiding test. The secondary outcome was the reliability of the voiding video test compared with maximum urinary flow rate assessed by uroflowmetry. Results: Thirty-one patients with hypospadias were enrolled. The patients' average ages were 12.3±3.2 months (range, 8-21 months) and 42.8±3.9 months (range, 35-48 months) at the time of surgery and voiding video tests, respectively. Hypospadias was anterior, penile, and proximal in 1 (3.2%), 18 (58.1%), and 12 (38.7%) patients, respectively. The number of patients with each voiding stream grade was as follows: very poor, 4; poor, 4; fair, 13; good, 4; and very good, 6. All intraclass correlation coefficients of the stream grade among the three observers were >0.95. Correlation between the maximum flow rate obtained by use of conventional uroflowmetry and the video voiding stream grade was validated (rho 0.778, p<0.001). Conclusions: The home-based guardian-conducted video voiding test is easy to perform and the present results demonstrate its validity and reliability for assessing patients' post-urethroplasty voiding pattern.

Reactive oxygen species affect spinal cell type-specific synaptic plasticity in a model of neuropathic pain.

Spinal synaptic plasticity is believed to drive central sensitization that underlies the persistent nature of neuropathic pain. Our recent data showed that synaptic plasticity in the dorsal horn is cell type specific: intense afferent stimulation produced long-term potentiation (LTP) in excitatory spinothalamic tract neurons (STTn), whereas it produced long-term depression (LTD) in inhibitory GABAergic interneurons (GABAn). In addition, reactive oxygen species (ROS) were shown to be involved in LTP in STTn (STTn-LTP) and in LTD in GABAn (GABAn-LTD). This study examined the roles of 2 biologically important ROS--superoxide [·O2] and hydroxyl radicals [·OH]--in neuropathic mechanical hyperalgesia and cell type-specific spinal synaptic plasticity. The [·O2] donor induced stronger mechanical hyperalgesia than the [·OH] donor in naive mice. The [·O2] scavenger showed greater antihyperalgesic effect than [·OH] scavengers in the spinal nerve ligation (SNL) mouse model of neuropathic pain. In addition, the [·O2] donor induced both STTn-LTP and GABAn-LTD, but the [·OH] donor induced only GABAn-LTD. On the other hand, the [·O2] scavenger inhibited STTn-LTP and GABAn-LTD induction in naive mice and alleviated SNL-induced potentiation in STTn and depression in GABAn. The [·OH] scavenger, however, inhibited depression in GABAn but did not interfere with potentiation in STTn. These results indicate that mechanical hyperalgesia in SNL mice is the result of the combination of STTn-LTP and GABAn-LTD. Behavioral outcomes compliment electrophysiological results which suggest that [·O2] mediates both STTn-LTP and GABAn-LTD, whereas [·OH] is involved primarily in GABAn-LTD.

Induction of long-term potentiation and long-term depression is cell-type specific in the spinal cord.

The underlying mechanism of chronic pain is believed to be changes in excitability in spinal dorsal horn (DH) neurons that respond abnormally to peripheral input. Increased excitability in pain transmission neurons, and depression of inhibitory neurons, are widely recognized in the spinal cord of animal models of chronic pain. The possible occurrence of 2 parallel but opposing forms of synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD) was tested in 2 types of identified DH neurons using whole-cell patch-clamp recordings in mouse spinal cord slices. The test stimulus was applied to the sensory fibers to evoke excitatory postsynaptic currents in identified spinothalamic tract neurons (STTn) and GABAergic neurons (GABAn). Afferent conditioning stimulation (ACS) applied to primary afferent fibers with various stimulation parameters induced LTP in STTn but LTD in GABAn, regardless of stimulation parameters. These opposite responses were further confirmed by simultaneous dual patch-clamp recordings of STTn and GABAn from a single spinal cord slice. Both the LTP in STTn and the LTD in GABAn were blocked by an NMDA receptor antagonist, AP5, or an intracellular Ca chelator, BAPTA. Both the pattern and magnitude of intracellular Ca after ACS were almost identical between STTn and GABAn based on live-cell calcium imaging. The results suggest that the intense sensory input induces an NMDA receptor-dependent intracellular Ca increase in both STTn and GABAn, but produces opposing synaptic plasticity. This study shows that there is cell type-specific synaptic plasticity in the spinal DH.

Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat.

We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation-induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind-paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group-I metabotropic Glu receptor (mGluR) antagonists and group-II mGluR agonist but not AMPA/kainate receptor antagonist prevented ES-induced hypersensitivity. I.pl. injection of PKA or PKC inhibitors also prevented ES-induced hypersensitivity. When the same injections were administered after establishment of ES-induced hypersensitivity, hypersensitivity was partially reduced by NMDAR antagonist only. In naïve animals, i.pl. Glu injection into the L4 dermatome induced tactile hypersensitivity, which was blocked by NMDAR antagonist and PKA and PKC inhibitors. These results suggest that the peripheral release of Glu, induced by antidromic nerve stimulation, leads to the expansion of tactile hypersensitive skin probably via nociceptor sensitization spread due to the diffusion of Glu into the skin near the release site. In addition, intracellular PKA- and PKC-dependent mechanisms mediated mainly by NMDAR activation are involved in Glu-induced nociceptor sensitization and subsequent hypersensitivity.