Genetic Variants in KCTD1 Are Associated with Isolated Dental Anomalies.

KCTD1 plays crucial roles in regulating both the SHH and WNT/ß-catenin signaling pathways, which are essential for tooth development. The objective of this study was to investigate if genetic variants in KCTD1 might also be associated with isolated dental anomalies. We clinically and radiographically investigated 362 patients affected with isolated dental anomalies. Whole exome sequencing identified two unrelated families with rare (p.Arg241Gln) or novel (p.Pro243Ser) variants in KCTD1. The variants segregated with the dental anomalies in all nine patients from the two families. Clinical findings of the patients included taurodontism, unseparated roots, long roots, tooth agenesis, a supernumerary tooth, torus palatinus, and torus mandibularis. The role of Kctd1 in root development is supported by our immunohistochemical study showing high expression of Kctd1 in Hertwig epithelial root sheath. The KCTD1 variants in our patients are the first variants found to be located in the C-terminal domain, which might disrupt protein-protein interactions and/or SUMOylation and subsequently result in aberrant WNT-SHH-BMP signaling and isolated dental anomalies. Functional studies on the p.Arg241Gln variant are consistent with an impact on ß-catenin levels and canonical WNT signaling. This is the first report of the association of KCTD1 variants and isolated dental anomalies.

Prenatal diethylstilbestrol induces malformation of the external genitalia of male and female mice and persistent second-generation developmental abnormalities of the external genitalia in two mouse strains.

Potential trans-generational influence of diethylstilbestrol (DES) exposure emerged with reports of effects in grandchildren of DES-treated pregnant women and of reproductive tract tumors in offspring of mice exposed in utero to DES. Accordingly, we examined the trans-generational influence of DES on development of external genitalia (ExG) and compared effects of in utero DES exposure in CD-1 and C57BL/6 mice injected with oil or DES every other day from gestational days 12 to 18. Mice were examined at birth, and on 5-120 days postnatal to evaluate ExG malformations. Of 23 adult (>60 days) prenatally DES-exposed males, features indicative of urethral meatal hypospadias (see text for definitions) ranged from 18% to 100% in prenatally DES-exposed CD-1 males and 31% to 100% in prenatally DES-exposed C57BL/6 males. Thus, the strains differed only slightly in the incidence of male urethral hypospadias. Ninety-one percent of DES-exposed CD-1 females and 100% of DES-exposed C57BL/6 females had urethral-vaginal fistula. All DES-exposed CD-1 and C57BL/6 females lacked an os clitoris. None of the prenatally oil-treated CD-1 and C57BL/6 male and female mice had ExG malformations. For the second-generation study, 10 adult CD-1 males and females, from oil- and DES-exposed groups, respectively, were paired with untreated CD-1 mice for 30 days, and their offspring evaluated for ExG malformations. None of the F1 DES-treated females were fertile. Nine of 10 prenatally DES-exposed CD-1 males sired offspring with untreated females, producing 55 male and 42 female pups. Of the F2 DES-lineage adult males, 20% had exposed urethral flaps, a criterion of urethral meatal hypospadias. Five of 42 (11.9%) F2 DES lineage females had urethral-vaginal fistula. In contrast, all F2 oil-lineage males and all oil-lineage females were normal. Thus, prenatal DES exposure induces malformations of ExG in both sexes and strains of mice, and certain malformations are transmitted to the second-generation.

Comparative effects of neonatal diethylstilbestrol on external genitalia development in adult males of two mouse strains with differential estrogen sensitivity.

The effect of neonatal exposure to diethylstilbestrol (DES), a potent synthetic estrogen, was examined to evaluate whether the CD-1 (estrogen insensitive, outbred) and C57 (estrogen sensitive, inbred) mouse strains differ in their response to estrogen disruption of male ExG differentiation. CD-1 and C57BL/6 litters were injected with sesame oil or DES (200 ng/g/5 µl in sesame oil vehicle) every other day from birth to day 10. Animals were sacrificed at the following time points: birth, 5, 10 and 60 days postnatal. Neonatally DES-treated mice from both strains had many ExG abnormalities that included the following: (a) severe truncation of the prepuce and glans penis, (b) an abnormal urethral meatus, (c) ventral tethering of the penis, (d) reduced os penis length and glans width, (e) impaired differentiation of cartilage, (f) absence of urethral flaps, and (g) impaired differentiation of erectile bodies. Adverse effects of DES correlated with the expression of estrogen receptors within the affected tissues. While the effects of DES were similar in the more estrogen-sensitive C57BL/6 mice versus the less estrogen-sensitive CD-1 mice, the severity of DES effects was consistently greater in C57BL/6 mice. We suggest that many of the effects of DES, including the induction of hypospadias, are due to impaired growth and tissue fusion events during development.

Prolapsed bladder following rupture of patent urachal cyst, mimicking bladder exstrophy: a case report and literature review.

A 26-year-old pregnant woman was diagnosed with fetal bladder prolapse following rupture of a patent urachus/urachal cyst, based on the finding of cyst disappearance with replacement with an infra-umbilical, extra-abdominal solid soft-tissue mass, mimicking bladder exstrophy. The neonatal findings confirmed the prenatal diagnosis. The baby was healthy and had a successful surgical correction. This report provides clues to differentiating ruptured bladder prolapse from bladder exstrophy as follows: (1) well-documented urachal cyst with urine-filled mass in the early gestation, (2) development of solid soft-tissue mass shortly after disappearance of the urachal cyst, and (3) no other structural abnormalities (bladder exstrophy is usually associated with abnormal genitalia, epispadias, or pubic diastasis). This study underlines the differentiation between the two entities because of the vast difference in prognosis, management, and proper counseling.

To investigate the correlation between the visual prostate symptom score, the international prostate symptom score, and uroflowmetry parameters in adult Thai males of different educational levels.

BACKGROUND: To evaluate the correlation between the International Prostate Symptom Score (IPSS), Visual Prostate Symptom Score (VPSS), and uroflowmetry parameters in Thai males and to examine the possibility in establishing a severity cut-off point for VPSS. METHODS: Between 1st February and 31st May 2016 a total of 200 men were enrolled onto the study and divided into high and low educated groups. All of them were requested to complete paperwork including their personal data, and then to complete a VPSS and IPSS questionnaire. Uroflowmetry, residual urine and prostate size were measured. The relationship between the answers to the VPSS and IPSS together with the other objective parameters was assessed using Spearman's rank test. RESULTS: The mean age of the patients was 61.2 years. 69.9% of subjects were highly educated. There was a statistically significant correlation between VPSS and IPSS in total, and any individual scores except frequency score. There was weak correlation between the VPSS and the uroflowmetry parameters and prostate size. The low educated group had a statistically significant lower completion rate of both the VPSS (41.6% vs. 79.8%) and IPSS (61.2% vs. 81.2%) without assistance than the higher educated group and most of the lower educated group felt that the IPSS was easier to understand than the VPSS (51.2% vs. 48.8%, P < 0.001). A VPSS severity score ≤6 or ≥14 had a very high specificity that predicted the patients would have mild or severe symptoms (94.7% and 98.6%) while a VPSS between 7 and 13 had a high sensitivity (90.8%) but a low specificity (16.9%) when it came to the prediction of moderate symptoms. CONCLUSION: VPSS showed a significant correlation to the IPSS and uroflowmetry parameters. A VPSS score ≤6, 7 to 13 and ≥14 may indicate mild, moderate, and severe symptoms respectively.

Conventional laparoscopic partial nephrectomy for a small renal mass.

The authors report the first case series of conventional laparoscopic partial nephrectomy in Thailand Laparoscopic partial nephrectomy was successfully performed in two patients with small renal tumors. The first patient underwent transperitoneal laparoscopic partial nephrectomy for a 3.8 x 3.3 cm renal mass. Intraoperative blood loss was 100 ml with warm ischemic time of 38 minutes. Pathological report showed renal cell carcinoma. The patient proceeded with laparoscopic radical nephrectomy, as surgical margin was not free. The second patient underwent retroperitoneal laparoscopic partial nephrectomy for a 1.8 x 2.4 cm renal mass. Intra-operative blood loss was 200 ml with clamping time of 45 minutes. Pathological report showed angiomylipoma. Using two different approaches of laparoscopy, namely, transperitoneal and retroperitoneal approaches, patients gained benefit from small incision and fast recovery.

A role of intravesical capsaicin instillation in benign prostatic hyperplasia with overactive bladder symptoms: the first reported study in the literature.

OBJECTIVE: To study the efficacy of capsaicin in treating overactive bladder symptoms in benign prostatic hyperplasia patients. MATERIAL AND METHOD: A prospective study of 20 benign prostatic hyperplasia patients whose overactive bladder symptoms were not improved by alpha1 blocker Alpha1 blocker was taken about 22.9 +/- 17.2 months before and continued throughout 6 months duration of the present study. All of them had undergone intravesical capsaicin instillation at the Faculty of Medicine Siriraj Hospital, Bangkok, from 2004 to 2006. Both clinical and urodynamic data were evaluated before and after treatment. RESULTS: Mean urgency decreased from 6.7 +/- 5.1 at baseline to 2.0 +/- 2.3 (p < 0.005), 1.4 +/- 2.4 (p < 0.005), 1.3 +/- 2.2 (p < 0.005) at 1, 3 and 6 months. Mean urge incontinence decreased from 1.7 +/- 3.5 at baseline to 0.5 +/- 1.3 (p = 0.148), 0.4 +/- 1.2 (p = 0.114), 0.3 + 1.1 (p = 0.085) at 1, 3 and 6 months. Mean urinary frequency decreased from 13.7 +/- 3.3 at baseline to 10.5 +/- 2.8 (p < 0.005), 9.6 +/- 2.0 (p < 0.005), 9.5 +/- 2.6 (p < 0.005) at 1, 3 and 6 months. Mean nocturia decreased from 4.7 +/- 2.4 at baseline to 3.1 +/- 2.2 (p < 0.005), 2.7 +/- 1.2 (p < 0.005), 2.9 +/- 1.6 (p < 0.005) at 1, 3 and 6 months. Mean first desire to void increased from 172.5 +/- 100.4 ml at baseline to 210.6 +/- 99.5 ml (p = 0.016) at 1 month. Mean maximal cystometric capacity increased from 350.3 +/- 165.9 ml at baseline to 397.4 +/- 165.7 ml (p = 0.012) at 1 month. Peak flow rate, detrusor pressure, and postvoid residual urine were not affected. No serious adverse effect occurred in the present study. CONCLUSION: Intravesical capsaicin instillation is an effective treatment for overactive bladder symptoms in benign prostatic hyperplasia patients.

A role of intravesical capsaicin instillation in benign prostatic hyperplasia with overactive bladder symptoms: the first reported study in the literature.

OBJECTIVE: To study the treatment efficacy of capsaicin, in the cases of benign prostatic hyperplasia with overactive bladder symptoms. MATERIAL AND METHOD: A prospective study of 20 benign prostatic hyperplasia patients whose overactive bladder symptoms were not improved by alpha1 blockers. All of them underwent intravesical capsaicin instillation at the Faculty of Medicine Siriraj Hospital, Bangkok, between 2004 and 2006. Both clinical and urodynamic data were evaluated before and after treatment. RESULTS: Mean urgency decreased from 6.7 +/- 5.1 at baseline to 2.0 +/- 2.3 (p < 0.005), 1.4 +/- 2.4 (p < 0.005), and 1.3 +/- 2.2 (p < 0.005) at 1, 3, and 6 months. Mean urge incontinence decreaseD from 1.7 +/- 3.5 at baseline to 0.5 +/- 1.3 (p = 0.148), 0.4 +/- 1.2 (p = 0.114), and 0.3 +/- 1.1 (p = 0.085) at 1, 3, and 6 months. Mean urinary frequency decreased from 13.7 +/- 3.3 at baseline to 10.5 +/- 2.8 (p < 0.005), 9.6 +/- 2.0 (p < 0.005), and 9.5 +/- 2.6 (p < 0.005) at 1, 3, and 6 months. Mean nocturia decreased from 4.7 +/- 2.4 at baseline to 3.1 +/- 2.2 (p < 0.005), 2.7 +/- 1.2 (p < 0.005), and 2.9 +/- 1.6 (p < 0.005) at 1, 3, and 6 months. Mean first desire to void increased from 172.5 +/- 100.4 ml at baseline to 210.6 +/- 99.5 ml (p = 0.016) at 1 month. Mean maximal cystometric capacity increased from 350.3 +/- 165.9 ml at baseline to 397.4 +/- 165.7 ml (p = 0.012) at 1 month. Peak flow rate, detrusor pressure, and post void residual urine were not affected No serious adverse effect occurred in this study. CONCLUSION: Intravesical capsaicin instillation is an effective treatment for overactive bladder symptoms in benign prostatic hyperplasia patients.

Fornix Rupture in Duplex Kidney due to Internal Iliac Artery Aneurysm.

A 70-year-old man presented with severe pain on the right side of the abdomen for 7 days. An abdominal CT angiographic scan showed an impending rupture of a large right internal iliac artery aneurysm which compressed to a right ureter causing hydroureteronephrosis. Fornix rupture of a right duplex kidney was also detected. Selective embolization of right gluteal arteries and then ligation of the right internal iliac artery and right ureterotomy with double J stenting were performed. At the 4-month follow-up appointment, an abdominal ultrasound demonstrated a decrease in the size of the aneurysm and no hydroureteronephrosis after the removal of double J stent.

Analysis of the effect of estrogen/androgen perturbation on penile development in transgenic and diethylstilbestrol-treated mice.

Because both androgens and estrogens have been implicated in penile morphogenesis, we evaluated penile morphology in transgenic mice with known imbalance of androgen and estrogen signaling using scanning electron microscopy (SEM), histology, and immunohistochemistry of androgen and estrogen receptors α/ß. Penises of adult wild-type, estrogen receptor-α knockout (αERKO), estrogen receptor-ß knockout (ßERKO), aromatase knockout (Arom-KO), and aromatase overexpression (Arom+) mice were evaluated, as well as adult mice treated with diethylstilbestrol (DES) from birth to day 10. Adult penises were examined because the adult pattern is the endpoint of development. The urethral orifice is formed by fusion of the MUMP (male urogenital mating protuberance) with the MUMP ridge, which consists of several processes fused to each other and to the MUMP. Similarly, the internal prepuce is completed ventrally by fusion of a ventral cleft. In adult murine penises the stromal processes that form the MUMP ridge are separated from their neighbors by clefts. αERKO, ßERKO, and Arom-KO mice have penises with a MUMP ridge clefting pattern similar to that of wild-type mice. In contrast, Arom+ mice and neonatally DES-treated mice exhibit profound malformations of the MUMP, MUMP ridge clefting pattern, and internal prepuce. Abnormalities observed in Arom+ and neonatally DES-treated mice correlate with the expression of estrogen receptor-beta (ERß) in the affected structures. This study demonstrates that formation of the urethal orifice and internal prepuce is due to fusion of separate epithelial-surfaced mesenchymal elements, a process dependent upon both androgen and estrogen signaling, in which ERß signaling is strongly implicated.

Idiopathic high-flow priapism in a pediatric patient.

High-flow priapism is a very rare condition in children. The most common cause is perineal trauma, which is a major cause of arterio-cavernosal fistula. A few pediatric patients have high-flow priapism without an obvious cause. There are many therapeutic modalities for this condition, depending on the etiology. We report a case of idiopathic high-flow priapism in a 6-year-old boy who underwent repeated superselective embolization.