Introducing an lsoprenaline Eluting Guidewire: Report on its Design and the Results of the Dose-Determining Pilot Study.

Introduction: Retrograde intrarenal surgery (RIRS) is associated with complications, many of which are related to the intrarenal pressure (IRP). We aim to describe the design of a novel isoprenaline-eluting guidewire ("IsoWire") and present the results from the first in vitro release studies and the first animal studies showing its effect on IRP. Materials and Methods: The IsoWire comprises a Nitinol core surrounded by a stainless-steel wire wound into a tight coil. The grooves created by this coil provided a reservoir for adding a hydrogel coating into which isoprenaline, a beta-agonist, was loaded. Animal studies were performed using a porcine model. For the control, IRP, heart rate (HR), and mean arterial pressure (MAP) were measured continuously for 6 minutes with a standard guidewire in place. For the experiment, the standard hydrophilic guidewire was removed, the IsoWire was inserted into the renal pelvis, and the same parameters were measured. Results: In vitro analysis of the isoprenaline release profile showed that most (63.9 ± 5.9%) of the loaded drug mass was released in the 1st minute, and almost all of the drug was released in the first 4 minutes exponentially. Porcine studies showed a 25.1% reduction in IRP in the IsoWire that released 10 µg in the 1st minute; however, there was a marked increase in HR. The average percentage reduction in IRP was 8.95% and 21.3% in the IsoWire that released 5 and 7.5 µg of isoprenaline, respectively, with no changes in HR or MAP. Conclusions: The IsoWire, which releases 5 and 7.5 µg of isoprenaline in the 1st minute, appears to be safe and effective in reducing the IRP. Further studies are needed to establish whether the isoprenaline-induced ureteral relaxation will render easier insertion of a ureteral access sheath, reduce IRP during sheathless RIRS, or even promote the practice of sheathless RIRS.

Hydrogen peroxide bladder irrigation: A simple, safe and effective management option for clot retention.

While the historical benefits of hydrogen peroxide on wounds and wound healing have recently been questioned, physicians have started to explore its other potential medicinal benefits. We present a case of a 14-year-old girl who presented to our urology unit with macroscopic haematuria and clot retention. Ultrasonography confirmed a large organised intravesical blood clot. Despite numerous attempts, manual bladder irrigation was unsuccessful and caused significant discomfort to the patient. Her clot retention was relieved after 4 irrigation cycles with a 3 % hydrogen peroxide solution. She experienced no complications or side effects post intravesical instillation of hydrogen peroxide.

Liver cystic echinococcosis: a parasitic review.

Liver cystic echinococcosis (CE), known as hydatid disease, is caused by the tapeworm Echinococcus granulosus sensu lato. Humans are accidental hosts in this zoonotic disease process, and hepatic infection accounts for over two-thirds of all cases. Since signs and symptoms are mainly non-specific, especially in early disease, clinicians should have a low threshold to include CE as a differential diagnosis in patients with positive serology and suggestive radiological findings, especially in endemic regions. The standard management for liver CE depends on the patient's symptoms, the radiological stage, the size and location of the cyst, the presence of complications and the treating clinicians' expertise. In this review, we discuss the lifecycle of Echinococcus granulosus sensu lato and its epidemiology and then focus on discussing the clinical features, diagnosis and treatment options of CE of the liver.

Cytomegalovirus haemorrhagic cystitis in a pregnant patient with AIDS.

Cytomegalovirus (CMV), an AIDS defining disease, has a high seroprevalence in the general population, while symptomatic infections occur mostly in immunocompromised individuals. Symptomatic CMV infections commonly include pneumonia, encephalitis, retinitis and colitis, while urinary tract involvement is a rare entity. We present a rare case of massive macroscopic haematuria due to CMV haemorrhagic cystitis in a 29-year-old woman in her second trimester of pregnancy. She was treated with intravenous Ganciclovir after initial resuscitation, and her symptoms promptly resolved. Timely diagnosis and treatment of symptomatic CMV infection is necessary to prevent associated morbidity, and this is especially significant during pregnancy in order to prevent foetal transmission. Both our patient and her baby remained symptom free at the 6-month follow-up post-delivery. Clinicians should have a high index of suspicion to biopsy the bladder urothelium of at-risk patients who present with haemorrhagic cystitis and have non-specific cystoscopy findings as histopathological analysis is the mainstay of diagnosing CMV-cystitis.

Inflammatory myofibroblastic tumour of the bladder: a case report and review of the literature.

Inflammatory myofibroblastic tumours (IMTs) are rare neoplasms of uncertain malignant potential that closely resemble other more aggressive spindle cell tumours. The distinction of IMT from the latter is of importance. We report a case of IMT in a 27-year-old man who presented with intermittent painless, macroscopic haematuria and was found to have a large bladder mass arising from the dome of the bladder. The tumour was resected transurethrally, and histology and immunohistochemistry were consistent with an IMT of the bladder. Our patient remained asymptomatic at follow-up 3 months later, when cystoscopy noted no regrowth of the residual tumour. Transurethral resection resection of bladder tumour, partial cystectomy and radical cystectomy form the mainstay of treatment of IMT. However, the optimal management of this condition remains uncertain due to the sparsity of reported cases.

TFE3-rearranged renal cell carcinoma with osseous metaplasia and indolent behaviour.

TFE3-rearranged renal cell carcinoma (RCC) is a rare but well characterised histological subtype of RCC with an aggressive clinical course and propensity for late metastases. Osseous metaplasia is an uncommon but well documented finding in clear cell, papillary and chromophobe RCC. We present the first case of a TFE3-rearranged RCC to be found harbouring metaplastic bone in a 47-year-old woman who presented with a slowly enlarging left flank mass over a 10 year period. This case report adds to the clinicopathological description of TFE3-rearranged RCC and suggests that larger studies are required to fully elucidate the prognosis of these tumours.

Metastatic prostate carcinoma presenting as a gluteal soft tissue mass.

Metastatic lesions from prostate adenocarcinoma to the bone and lymph nodes and less frequently to the lungs, pleura, liver and adrenal glands are well documented. The presence of soft tissue metastases from a prostate adenocarcinoma is extremely rare. We report a case of a 56-year-old male who presented with a 2-year history of a painless buttock mass. MRI showed a well-defined, right gluteal intermuscular soft tissue mass and multifocal hypointense lesions of the pelvic bones and appendicular skeleton suggestive of secondary metastatic disease. Tru-cut biopsy of the gluteal mass demonstrated metastatic adenocarcinoma. Further workup showed an elevated prostate-specific antigen, and acinar adenocarcinoma of the prostate was confirmed on transrectal biopsy of the prostate. Androgen deprivation therapy with long-acting three monthly goserelin and short-term cover with bicalutamide was initiated as was systemic taxane-based chemotherapy. He has shown an excellent PSA response and remains asymptomatic with complete resolution of the size of the gluteal metastasis at the most recent follow-up 9 months later.

Wilms' tumour with spinal cord involvement.

Spinal cord involvement of Wilms' tumour is rare. A 14-year-old girl presented with an abdominal mass, paraplegia and loss of bladder and bowel control. Radiological investigations confirmed the presence of a large intraabdominal mass with infiltration into the spinal canal with impingement of nerve roots and the spinal cord. Histopathological evaluation demonstrated a nephroblastoma. It was decided to commence prompt neoadjuvant chemotherapy to render the tumour amenable to surgical resection. The patient unfortunately demised before receiving her first dose. Early diagnosis and timeous initiation of treatment is critical in limiting morbidity and mortality associated with malignant spinal cord compression.

Pulmonary lymphangioleiomyomatosis with an associated giant renal angiomyolipoma.

Pulmonary lymphangioleiomyomatosis (LAM), a rare, progressive disease predominantly affecting the lungs of women of reproductive age, is often associated with renal angiomyolipoma (AML). We report the case of a 29-year-old female patient who presented to our obstetrics department at 37 weeks' gestation, complaining of abdominal pain, and constipation. Ultrasound noted a viable singleton with a large left-sided abdominal mass. After undergoing a caesarean section, she was referred to our urology department to assess her flank mass further. Computed tomography demonstrated a large, exophytic left renal mass measuring 22 cm x 16 cm x 13 cm, suggestive of an AML and numerous bilateral pulmonary cysts. A diagnosis of LAM and associated unilateral giant renal AML was made. As soon as she had fully recovered from her caesarean section, we removed the huge AML via a standard left-sided open nephrectomy without incident. We report this rare case of giant AML associated with LAM and review the literature about the association of these two conditions.

Lytic parasitic: a case of bone destructing echinococcosis.

Pelvic hydatid bone disease is a rare and debilitating condition. Patients often present with symptoms and signs when the disease process is advanced and curative resection is not possible. We present a case of destructive bone hydatid disease affecting the left iliac bone. A 45-year-old woman presented initially 5 years ago with a left pelvic mass to the gynaecology department. Computed tomography (CT) scan done at that time showed a large pelvic, left iliac fossa cystic mass with the destruction of the left iliac bone. Extension of the cystic mass transversed the iliac bone into the posterior soft tissue. Percutaneous biopsy taken showed hydatid cystic disease. The patient was planned for surgery and, however, was lost to follow-up. Four years later, she presented with a history of worsening left pelvic pain with an enlarging, left pelvic mass, and another mass in the posterior gluteal area. In addition, CT imaging showed extensive left iliac bone destruction with posterior soft tissue extension to the gluteus muscle. A multidisciplinary team concluded that complete excision would not result in cure. Thus, complete iliac wing bone reconstruction was not an option in this patient. Instead, palliative measures were deemed in the patient's best interest to control disease progression and relieve painful pressure-related symptoms from the hydatid cystic mass. The patient received preoperative albendazole and underwent an extraperitoneal debulking of the soft tissue hydatid infiltration and debridement of bony fragments from left iliac bone destruction. Postoperatively, the patient did well, and her main complaint of pain related to the cystic mass pressure had improved significantly.

Priapism after spinal cord injury - a case report and review of the literature.

Involuntary unwanted erections are extremely rare after spinal cord injury (SCI). A sudden loss of sympathetic tone to the pelvic vasculature following SCI causes an increase in the parasympathetic tone and uncontrolled arterial blood flow into the penile sinusoidal spaces. When occurring immediately after an acute SCI, it is generally self-limiting and settles within a few hours. In contrast, recurrent, unwanted erections in patients with chronic SCI are more unpredictable in frequency and duration and may require treatment. We present a case of recurrent involuntary unwanted erections in a patient with chronic SCI after a stab wound to his neck and review the pathophysiology and available management options.

Florid cystitis cystica et glandularis causing irreversible renal injury.

Cystitis cystica et glandularis (CCEG) is widely believed to be innocuous and self-limiting. We report a case of a 32-year-old male patient who was found to have gross bilateral hydroureter and hydronephrosis and an estimated glomerular filtration rate of 3 ml/min/1.73 m2. Cystoscopy revealed extensive cystic and nodular lesions involving most of the bladder urothelium, which proved to be CCEG on histopathological analysis. Retrograde and anterograde stents could not be inserted due to obstruction of the ureters at the level of the vesicoureteric junction. Percutaneous nephrostomies were subsequently inserted. Although there was evidence of improvement of the CCEG on follow-up cystoscopy, no improvement of renal function, despite decompression with percutaneous nephrostomies, was seen. He was subsequently placed on the waiting list for a renal transplant. We believe this to be the only known case reported of florid CCEG obstructing the upper urinary tracts bilaterally, causing irreversible renal injury.

Urethral polyembolokoilamania: not a bread-and-butter issue.

Urethral polyembolokoilamania, the self-insertion of a foreign body into the male urethra for sexual gratification and autoerotism, is an uncommon urological emergency with potentially severe consequences. We present the case of a 27-year-old male who presented to our emergency unit after apparently sustaining a penile injury during sexual intercourse. Clinically, a foreign body was thought to be palpable, extending from the mid-shaft of the penis to the penoscrotal junction. Pelvic X-rays confirmed a radiopaque penile foreign body in the region of the anterior urethra. Cystoscopy confirmed the presence of an encrusted foreign body in the anterior urethra. It noted that the surrounding mucosa was very inflamed with areas of necrosis, suggesting that the foreign body had been present in the urethra for some time. To avoid further urethral trauma, we approached the foreign body via an external urethrotomy and removed a plastic knife in three parts. The urethra was repaired over a 16F catheter. The patient had an uneventful postoperative course, and a peri-catheter urethrogram 6 weeks after the procedure showed no signs of contrast extravasation or urethral stricture.

Presentation and surgical management of a superficial temporal artery pseudoaneurysm: A case report.

INTRODUCTION AND IMPORTANCE: A Superficial Temporal Artery Pseudoaneurysm is an uncommon, but important, differential diagnosis for masses in the head and neck region. This work has been reported in line with SCARE 2020 criteria [1]. CASE PRESENTATION: An 81-year-old male presented to the Oral and Maxillofacial Department with a facial swelling that had been present for a duration of three weeks. A provisional diagnosis of a haematoma was made and an ultrasound carried out to confirm diagnosis. Ultrasonography and CT Angiography confirmed a pseudoaneurysm arising from the left superficial temporal artery. CLINICAL DISCUSSION: Although this is a relatively uncommon diagnosis it is important to be aware of the key diagnostic tools used to identify a pseudoaneurysm. Specifically, their potential to exclude a pseudoaneurysm prior to diagnosing a simple post-traumatic haematoma. This is important as the treatment strategies for the two pathologies differ considerably. Useful learning points from this case include diagnostic aids such as the unique pulsatile nature of the mass and the role of ultrasonography and CT Angiography in confirming diagnosis and guiding surgical management. CONCLUSION: Pseudoaneurysms are an important consideration as a differential diagnosis of masses in the head and neck region. This case report may impact upon management of future similar cases by highlighting significant aspects of their clinical diagnosis and surgical management, enabling early identification and appropriate management.

Clear Cell Renal Cell Carcinoma with a Ureteral Thrombus.

Introduction: Cancers of the kidney, arising from either the renal parenchymal tissue or the renal pelvis, is among the 13 commonest types of malignancy globally, accounting for between 3% and 4% of all newly diagnosed cancers. Renal cell carcinoma (RCC) accounts for 85% of all malignant renal neoplasms. We present a rare case of an RCC directly extending into the renal pelvicalyceal system and with a thrombus within the ureter. Case Presentation: A 39-year-old woman presented with a long-standing history of worsening left flank pain, intermittent visible hematuria, and a fullness in the left flank. Apart from an ill-defined left flank mass with pain on palpation, there was nothing remarkable on clinical examination. Contrast-enhanced abdominal CT scan images showed a large, heterogeneously enhancing soft tissue mass arising from the lower pole of the left kidney. The collecting system and the left proximal ureter were poorly visualized. A tentative diagnosis of RCC, cT3aN0M0 was made. Intraoperatively, we identified a large, left lower pole renal mass, displacing the pedicle superiorly. In addition, we found a bulky, dilated proximal ureter. A decision was made intraoperatively to proceed with radical nephrectomy and ureterectomy. Conclusion: We report a rare case of RCC directly invading from the renal pelvis and down the ureter as a thrombus mass, with no microscopic individual tumor implants in the ureter wall, invasion of the renal vein, or invasion of adjacent organs. To our knowledge, only four such cases have been reported in English literature, and as a result, very few theories explaining renal pelvic invasion and direct growth down the ureter have been postulated. This highlights the significance of adding invasion of the pelvicalyceal system as part of the most recent, updated tumor node metastases classification. In future, consideration needs to be given to include the extension of RCC into the ureter and/or bladder.

Remodeling of HIV-1 Nef Structure by Src-Family Kinase Binding.

The HIV-1 accessory protein Nef controls multiple aspects of the viral life cycle and host immune response, making it an attractive therapeutic target. Previous X-ray crystal structures of Nef in complex with key host cell binding partners have shed light on protein-protein interactions critical to Nef function. Crystal structures of Nef in complex with either the SH3 or tandem SH3-SH2 domains of Src-family kinases reveal distinct dimer conformations of Nef. However, the existence of these Nef dimer complexes in solution has not been established. Here we used hydrogen exchange mass spectrometry (HX MS) to compare the solution conformation of Nef alone and in complexes with the SH3 or the SH3-SH2 domains of the Src-family kinase Hck. HX MS revealed that interaction with the Hck SH3 or tandem SH3-SH2 domains induces protection of the Nef αB-helix from deuterium uptake, consistent with a role for αB in dimer formation. HX MS analysis of a Nef mutant (position Asp123, a site buried in the Nef:SH3 dimer but surface exposed in the Nef:SH3-SH2 complex), showed a Hck-induced conformational change in Nef relative to wild-type Nef. These results support a model in which Src-family kinase binding induces conformational changes in Nef to expose residues critical for interaction with the µ1 subunit of adaptor protein 1 and the major histocompatibility complex-1 tail, and subsequent major histocompatibility complex-1 downregulation and immune escape of HIV-infected cells required for functional interactions with downstream binding partners.

Interaction with the Src homology (SH3-SH2) region of the Src-family kinase Hck structures the HIV-1 Nef dimer for kinase activation and effector recruitment.

HIV-1 Nef supports high titer viral replication in vivo and is essential for AIDS progression. Nef function depends on interactions with multiple host cell effectors, including Hck and other Src-family kinases. Here we describe the x-ray crystal structure of Nef in complex with the Hck SH3-SH2 regulatory region to a resolution of 1.86 Å. The complex crystallized as a dimer of complexes, with the conserved Nef PXXPXR motif engaging the Hck SH3 domain. A new intercomplex contact was found between SH3 Glu-93, and Nef Arg-105. Mutagenesis of Hck SH3 Glu-93 interfered with Nef·Hck complex formation and kinase activation in cells. The Hck SH2 domains impinge on the N-terminal region of Nef to stabilize a dimer conformation that exposes Asp-123, a residue critical for Nef function. Our results suggest that in addition to serving as a kinase effector for Nef, Hck binding may reorganize the Nef dimer for functional interaction with other signaling partners.

Discovery of a diaminoquinoxaline benzenesulfonamide antagonist of HIV-1 Nef function using a yeast-based phenotypic screen.

BACKGROUND: HIV-1 Nef is a viral accessory protein critical for AIDS progression. Nef lacks intrinsic catalytic activity and binds multiple host cell signaling proteins, including Hck and other Src-family tyrosine kinases. Nef binding induces constitutive Hck activation that may contribute to HIV pathogenesis by promoting viral infectivity, replication and downregulation of cell-surface MHC-I molecules. In this study, we developed a yeast-based phenotypic screen to identify small molecules that inhibit the Nef-Hck complex. RESULTS: Nef-Hck interaction was faithfully reconstituted in yeast cells, resulting in kinase activation and growth arrest. Yeast cells expressing the Nef-Hck complex were used to screen a library of small heterocyclic compounds for their ability to rescue growth inhibition. The screen identified a dihydrobenzo-1,4-dioxin-substituted analog of 2-quinoxalinyl-3-aminobenzene-sulfonamide (DQBS) as a potent inhibitor of Nef-dependent HIV-1 replication and MHC-I downregulation in T-cells. Docking studies predicted direct binding of DQBS to Nef which was confirmed in differential scanning fluorimetry assays with recombinant purified Nef protein. DQBS also potently inhibited the replication of HIV-1 NL4-3 chimeras expressing Nef alleles representative of all M-group HIV-1 clades. CONCLUSIONS: Our findings demonstrate the utility of a yeast-based growth reversion assay for the identification of small molecule Nef antagonists. Inhibitors of Nef function discovered with this assay, such as DQBS, may complement the activity of current antiretroviral therapies by enabling immune recognition of HIV-infected cells through the rescue of cell surface MHC-I.

Effector kinase coupling enables high-throughput screens for direct HIV-1 Nef antagonists with antiretroviral activity.

HIV-1 Nef, a critical AIDS progression factor, represents an important target protein for antiretroviral drug discovery. Because Nef lacks intrinsic enzymatic activity, we developed an assay that couples Nef to the activation of Hck, a Src family member and Nef effector protein. Using this assay, we screened a large, diverse chemical library and identified small molecules that block Nef-dependent Hck activity with low micromolar potency. Of these, a diphenylpyrazolo compound demonstrated submicromolar potency in HIV-1 replication assays against a broad range of primary Nef variants. This compound binds directly to Nef via a pocket formed by the Nef dimerization interface and disrupts Nef dimerization in cells. Coupling of nonenzymatic viral accessory factors to host cell effector proteins amenable to high-throughput screening may represent a general strategy for the discovery of new antimicrobial agents.