Urethral fistulae following surgery for scrotal or perineal hypospadias: A 20-year review.

INTRODUCTION: Urethral fistulae (UF) following hypospadias surgery can be a frustrating complication with reports of even 15 attempts to close a difficult fistula (Richter 2003). UF occurring in scrotal or perineal hypospadias (SPH) pose a further challenge because of the under-virilised penis. OBJECTIVE: To review the outcomes of a single surgeon's experience over 20 years of managing UF in SPH. To analyse the traditional approach of fistula closure and three alternative techniques. MATERIALS AND METHODS: A prospectively maintained database of patients who underwent hypospadias surgery for SPH from January 1997 to September 2018 was reviewed. Patients with UF were identified and their data recorded. The techniques of fistula closure were: a-Traditional approach. b Purse-string closure. c. Right angle intersection technique where the skin and urethra are closed at right angles to each other. d Anchoring skin to corpora away from the fistula closure. RESULTS: 32 patients with 41 fistulae were identified. Follow-up ranged from 1 to 18 years. 10/32 (31%) had concomitant meatal stenosis or urethral strictures. The sites of UF were: penoscrotal 19/41 (46%), midpenile 14/41 (34%), coronal or subcoronal in 8/41 (20%). One fistula resolved spontaneously after a single urethral dilatation. 4 patients with a coronal fistula were laid open to the glandular meatus creating a coronal hypospadias, with redo-urethroplasty later (in 2 a buccal graft was used). Of the rest, 29 fistulae were cured after one surgery, while 7 needed two attempts. No patient needed more than two surgeries to close the fistula. The recurrence rates were as follows- Purse-string suture: 10%, Right angle intersection technique: 14.3%, Anchoring skin to corpora: 16.7%, Traditional approach: 21.7%. Although the purse-string suture technique had the lowest recurrence rate, the figures did not reach statistical significance (P-0.95). CONCLUSION: Urethral fistulae occurring in SPH pose challenges because of the under-virilised penis. A third of patients may have meatal stenosis or urethral strictures which must be identified and dealt with. The three novel techniques we employed helped drive down our recurrence rate. Purse string sutures reduce the weak area to a dot and are an excellent way to deal with small fistulae (<5 mm). Other innovations include offsetting the skin suture line by anchoring it to the penile shaft well away from the fistula repair or closing the fistula and skin at right angle to each other. The fact that no patient needed more than two operations to lose the UF, was gratifying.

Expression and purification of tau protein and its frontotemporal dementia variants using a cleavable histidine tag.

Recombinant tau protein is widely used to study the biochemical, cellular and pathological aspects of tauopathies, including Alzheimer's disease and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTPD-17). Pure tau in high yield is a requirement for in vitro evaluation of the protein's physiological and toxic functions. However, the preparation of recombinant tau is complicated by the protein's propensity to aggregate and form truncation products, necessitating the use of multiple, time-consuming purification methods. In this study, we investigated parameters that influence the expression of wild type and FTPD-17 pathogenic tau, in an attempt to identify ways to maximise expression yield. Here, we report on the influence of the choice of host strain, induction temperature, duration of induction, and media supplementation with glucose on tau expression in Escherichia coli. We also describe a straightforward process to purify the expressed tau proteins using immobilised metal affinity chromatography, with favourable yields over previous reports. An advantage of the described method is that it enables high yield production of functional oligomeric and monomeric tau, both of which can be used to study the biochemical, physiological and toxic properties of the protein.