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We present a case of intractable acute ischaemic priapism occurring secondary to newly commenced olanzapine. It demonstrates rapid intervention in a stepwise approach aiming to restore penile flaccidity in order to prevent chronic damage to the corpora cavernosa. After an unsuccessful conservative approach, our patient underwent two formal distal penile shunt procedures with no effective penile detumescence. Subsequently, bilateral proximal penile shunts were performed comprising a right corpus cavernosum to corpus spongiosum anastomosis and a left saphenous vein to left corpus cavernosum anastomosis. The patient remained an inpatient for observation, and detumescence was gradually achieved over several days after this procedure. However, follow-up revealed erectile dysfunction, and it was explained to the patient that he was unlikely to achieve further erections and that a penile implant was the only realistic option., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To report on the dosimetric benefits and late toxicity outcomes after injection of hydrogel spacer (HS) between the prostate and rectum for patients treated with prostate radiotherapy (RT)., Patients and Methods: In all, 76 patients with a clinical stage of T1-T3a prostate cancer underwent general anaesthesia for fiducial marker insertion plus injection of the HS into the perirectal space before intensity-modulated RT (IMRT) or volumetric-modulated arc RT (VMAT). HS safety, dosimetric benefits, and the immediate- to long-term effects of gastrointestinal (GI) toxicity were assessed., Results: There were no postoperative complications reported. The mean (range) prostate size was 66.0 (25.0-187.0) mm. Rectal dose volume parameters were observed and the volume of rectum receiving 70 Gy (rV 70 ), 75 Gy (rV 75 ) and 78 Gy (rV 78 ) was 7.8%, 3.6% and 0.4%, respectively. In all, 21% of patients (16/76) developed acute Grade 1 GI toxicities, but all were resolved completely by 3 months after treatment; whilst, 3% of patients (2/76) developed late Grade 1 GI toxicities. No patients had acute or late Grade ≥2 GI toxicities., Conclusion: Injection of HS resulted in a reduction of irradiated rectal dose volumes along with minimal GI toxicities, irrespective of prostate size., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Inguinal hernia is the most common congenital anomaly requiring surgical correction. The cause of the hernia is, most commonly, persistence of the processus vaginalis. Study of testicular descent in rodents has revealed a role for the genitofemoral nerve and calcitonin gene-related peptide (CGRP). Since the testis cannot descend without the processus vaginalis, we wondered whether both descent and hernia closure might be regulated by the same mechanism. Therefore, we tested the idea that CGRP might be active in closure of the inguinal hernia. Using hernial sacs removed at herniotomy operation, fusion of the hernial surfaces was induced by CGRP, but not by CGRP 8-37, CGRP 27-37 or dihydrotestosterone. Hepatocyte growth factor also caused peritoneal obliteration in vitro. We propose that obliteration of the processus vaginalis is under the control of molecules released from the genitofemoral nerve, and that a chemical treatment of inguinal hernia is at least theoretically possible.

By exposing rat fetuses to adriamycin prenatally, a rat model of VATER association has been created. Absence of the fetal bladder is prominent and the kidneys show features of chronic obstruction with hydronephrosis/hydroureter, loss of parenchyma, fewer glomeruli, and less differentiation. The aim of this study was to elucidate this rat model, to determine exactly when the changes in the kidneys develop, hopefully thereby to expand our understanding of congenital obstructive uropathy. Timed-pregnant Sprague-Dawley rats were injected intraperitoneally with adriamycin on days 6-9 of gestation. The control group received saline. Fetuses were recovered on gestational days (GDs) 20, 19, 18, 17, 16, 15, 14, 12, and 10 (total, 120 control, 121 treated). Macroscopic features were determined. Serial sections were then taken and stained with hematoxylin and eosin. Comparisons were made under light microscopy. The metanephric kidney first became apparent at GD12. The development of the control and treated kidneys appeared similar till GD18. Beyond this day, the treated kidneys exhibited increasing degrees of distension of Bowman's capsule, ducts, and subsequently pelvis and ureter. There were fewer levels of glomeruli, which were also less differentiated. Less differentiation was also noted in the medulla, and with time this became thin in comparison to the control kidneys. By GD20, the renal pelvis was grossly dilated with a blunted papilla, and the renal parenchyma was thin. Prenatal exposure of rat fetuses to adriamycin results in kidneys that are chronically obstructed, as the majority of the fetuses show absence of the bladder. Absence of renal dysmorphology until GD18, when urine is first produced, suggests strongly that the effect of adriamycin on the kidney is indirect, via agenesis of the bladder and secondary to backpressure from early urine production. This is a unique, simple, and reliable model of fetal obstructive uropathy and will be very useful to facilitate further investigation into its pathophysiology and to explore new treatment options., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: A rat model of the VATER (vertebral defects, anal atresia, tracheo-esophageal fistula with esophageal atresia, renal defects and radial limb dysplasia) association was created by exposing fetuses to doxorubicin early in gestation. Most fetuses had an absent bladder with ureters that were grossly dilated. We determined the effect of this absent bladder on kidneys development, particularly whether dysplasia was evident., Materials and Methods: Nine timed pregnant rats were injected intraperitoneally with doxorubicin at a dose of 2 mg/kg body weight on days 6 to 9 of gestation. The control group of 3 rats received saline. Fetuses were recovered on day 21 and examined macroscopically. Quantitative measurements were taken of renal wet and dry weights, renal length and ureteral diameter. Serial sections were then taken and stained alternately with hematoxylin and eosin or trichrome. The kidneys were compared under light microscopy. Comparisons between control and treated groups were made with the Student t test., Results: An absent bladder was confirmed in 50 of the 55 fetuses (91%). In most fetuses the kidneys were correctly located, although they were hydronephrotic and poorly developed. This finding was confirmed quantitatively with significant differences in treated and control fetuses in renal length (5.24 vs 4.13 mm, p <<0.01) and in the ratio of wet renal weight to body weight and dry weight (2.7 vs 3.4 mg, p <<0.01). Dilated, tortuous ureters were found bilaterally in most cases. Microscopically the kidneys had abnormal architecture and were less mature than in controls. Nephron induction was poor with abnormal configurations. Tubular differentiation was decreased and the medulla was thin and less cellular than in controls. Dilatation occurred mainly in the collecting system and ducts/tubules. There was no collagen deposition/fibrosis or aberrant tissue., Conclusions: In this rat model the kidneys are exposed to obstruction early in development since the bladder does not form. The resulting kidneys are hydronephrotic with decreased parenchyma and poor differentiation. However, there is no fibrosis or aberrant tissue.

The recently identified protein, insulin 3 (INSL3), has structural features that make it a bona fide member of the insulin superfamily. Its predicted amino acid sequence contains the classic two-peptide chain (A- and B-) structure with conserved cysteine residues that results in a disulphide bond disposition identical to that of insulin. Recently, the generation of insl3 knockout mice has demonstrated that testicular descent is blocked due to the failure of a specific ligament, the gubernaculum, to develop. The mechanism by which INSL3 exerts its action on the gubernaculum is currently unknown. The purpose of this study was to, for the first time, synthesize rat INSL3 and test its action on organ cultures of foetal rat gubernaculum. INSL3 also contains a cassette of residues Arg-X-X-X-Arg within the B-chain, a motif that is essential for characteristic activity of another related member of the superfamily, relaxin. Hence, the relaxin activity of rat INSL3 was also tested in two different relaxin bioassays. The primary structure of rat INSL3 was determined by deduction from its cDNA sequence and successfully prepared by solid phase peptide synthesis of the two constituent chains followed by their combination in solution. Following confirmation of its chemical integrity by a variety of analytical techniques, circular dichroism spectroscopy confirmed the presence of high beta-turn and alpha-helical content, with a remarkable spectral similarity to the synthetic ovine INSL3 peptide and to synthetic rat relaxin. The synthetic rat INSL3 bound with very low affinity to rat relaxin receptors and had no activity in a relaxin bioassay. Furthermore, it did not augment or antagonize relaxin activity. The rat INSL3 did however induce growth of foetal rat gubernaculum in whole organ cultures demonstrating that INSL3 has a direct action on this structure.

Purpose: Testicular descent is controlled by 2 morphological and hormonal steps. Transabdominal testicular descent is mediated by gubernacular swelling and regression of the cranial suspensory ligament. Müllerian inhibiting substance (MIS) has been proposed to stimulate the swelling but this remains controversial. Recently, a mouse mutant for Leydig insulin-like hormone (Insl3) was found to have undescended testis and deficient gubernaculum. We examine the testicular position of Insl3 mutant mice and the development of gubernacula., Materials and Methods: Mice with Insl3 homozygotes (-/-), heterozygotes (+/-) and wild-types (+/+) were examined at embryonic day 16.5 and birth. Macroscopic dissections and measurements of the testicular position, as well as microscopic analysis (hematoxylin and eosin, and Masson's trichrome) were performed., Results: Of the mice 11 Insl3 homozygote males had significantly impaired testicular descent at embryonic day 16.5 and birth (p <0.01), and the cord was thin and elongated, while 14 heterozygotes and 7 wild-types had normal testicular descent. Microscopically, the gubernaculum of Insl3 homozygotes was small with some muscle development but no central core of mesenchyme at embryonic day 16.5. On the other hand, heterozygotes and wild-types had normal gubernacular development with a swelling reaction., Conclusions: Insl3 mutants show feminized gubernaculum with deficient mesenchymal core. Insl3 appears to have some role in the gubernacular swelling reaction in mice.

Maternal mortality exceeding 50% and perinatal loss of more than 45% contraindicate pregnancy in females with Eisenmenger syndrome. Sterilization is the contraceptive method of choice. Any operation carries a very significant risk in persons with Eisenmenger syndrome; the anaesthetic mortality has been reported to be 19%. This paper details the successful sterilization of 4 women with Eisenmenger syndrome at our institution.