Perhexiline is a potent prophylactic anti-anginal agent that has been shown to inhibit myocardial utilization of long-chain fatty acids and to inhibit the mitochondrial enzyme carnitine palmitoyltransferase (CPT)-1. We compared the hemodynamic and biochemical effects of perhexiline (0.5 and 2.0 microM) and of another CPT-1 inhibitor, oxfenicine (0.5 mM), in Langendorff-perfused rat hearts subjected to 60 min of low-flow ischemia (95% flow reduction) followed by 30 min of reperfusion. Both perhexiline (2 microM only) and oxfenicine attenuated (p < 0.003, p < 0.0002, respectively) increases in diastolic tension during ischemia, without significant effects on developed tension, or on cardiac function during reperfusion. Myocardial concentrations of long-chain acylcarnitines (LCAC), products of CPT-1 action, were decreased (p < 0.05) by oxfenicine, unaffected by 2 microM perhexiline, and increased slightly by 0.5 microM perhexiline. Perhexiline, but not the active metabolite of oxfenicine, also inhibited cardiac CPT-2 with similar IC50 and Emax, although lower Hill slope, compared with CPT-1. Oxfenicine, but not perhexiline, reduced concentrations of the endogenous CPT-1 inhibitor, malonyl-CoA. Perhexiline, but not oxfenicine, inhibited myocardial release of lactate during normal flow. We conclude that (a) perhexiline protects against diastolic dysfunction during ischemia in this model, independent of major changes in LCAC accumulation and (b) this may result from simultaneous effects of perhexiline on myocardial CPT-1 and CPT-2.

One in three women will experience a clinically significant urinary tract infection (UTI) by age twenty-four and almost half will have at least one in their lifetime. Recurrent UTIs (rUTIs) are defined as having greater than two infections in a 6-month period, or three infections over twelve months, with complete resolution for at least two weeks. These may be due to relapse from incomplete treatment (persistence) or re-infection (new source). It may be difficult to distinguish between the two, where the same organism is cultured. There are several risk factors for rUTIs including an impairment of the body’s immune system and virulence factors. Reversible or treatable causes are sought and excluded in the patient’s initial review. Patient’s with rUTI are often complex and difficult to manage. The long-term management options in women are multimodal and should focus on prevention of relapse and recurrence. Behavioural factors include adequate hydration, care with sexual hygiene, reducing one’s body mass index (BMI) and post-void residual (PVR) volume. There are several non-antimicrobial options for rUTIs which have become a multi-billion-dollar business. Unfortunately, there are numerous studies which fail to show any major benefit or having conflicting data. Vaccines are currently being explored as a prevention strategy, delivered through injection, intra-nasal sprays, or vaginal suppositories, which are made from combinations of heat killed uro-pathogenic strains. There are no widely available vaccines at present due to limited clinical success. It is well established that appropriate antibiotic therapy results in higher rates of symptom relief and bacterial eradication in women with uncomplicated cystitis. There are several options for antimicrobial use which have been shown to be highly effective in reducing the risk of rUTI in women. The pain and discomfort of the UTI must be balanced with the cost and risk of developing resistance when using antimicrobials. Continuous prophylaxis, pre- and post-coital voiding, and self-starting are the three commonly accepted options for prophylaxis. The choice between these will depend upon patient preference, cultures and previous pattern of infection. Intra-vesical instillation of hyaluronic acid and chondroitin sulphate have been used for glycosaminoglycan (GAG) layer replenishment for many indications, including interstitial cystitis, overactive bladder syndrome, radiation cystitis and prevention of rUTI. At present, intra-vesical therapies are reserved for only those with the most unresponsive rUTIs. The principles of treating rUTI are to break the cycle and to treat any reversible causes. With our ever-expanding research knowledge, there are now many useful products that may be used for the successful treatment of rUTI. A management plan including a combination of a non-antimicrobial and selective antimicrobial regime for a minimum of six months should be considered. It is a prudent clinician that clearly defines this management plan, with reassurance of a finite peri...

There are many causes of recurrent urinary tract infections (rUTI) which are amenable to surgical management. This usually follows a lengthy trial of conservative management. Aetiological classification of rUTI requiring surgical management may be divided into congenital or acquired. Predisposing factors are classified into two groups; those providing a source for organisms, or by maintaining favourable conditions for the proliferation of organisms. Sources of infections include calculi, fistulae or abscesses. Conditions which predispose to bacterial proliferation include malignancies, foreign bodies, high post void residuals, and neuropathic bladders. Removal of identified sources, treating the obstruction, and improving urinary drainage, are all goals of surgical management. Surgical options for rUTI management can range from minimally invasive procedures such as endoscopic or percutaneous, through to more invasive requiring laparoscopic or an open approach. Surgery remains a very important and viable solution.

Iatrogenic splenic tear after a colonoscopy is a rare complication. Conditions predisposing to splenocolic adhesions such as previous abdominal surgery, pancreatitis, or inflammatory bowel disease may increase the risk of this injury after colonoscopy. We present a case of a 47-year-old woman with an iatrogenic splenic tear after a routine colonoscopy, who had several of these predisposing factors and required an urgent splenectomy.

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We present the case of a 53-year-old man, with a history of alcohol abuse, requiring intensive care unit admission, with an obstructing right upper renal calculus and Klebsiella pneumoniae urosepsis. Ureteroscopic treatment of this obstruction displayed a small calculus within the renal pelvis completely encapsulated within a fungal bezoar. Laboratory analysis of the fungal mass found it to be Candida dubliniensis.

Objectives To report a large series of vesicovaginal fistula, and to assess the incidence of ureteric injury in association with vesicovaginal fistula. Methods We retrospectively reviewed a prospective database of patients with vesicovaginal fistula referred to our center between 2004 and 2016. Data on patient demographics, fistula etiology, mode of repair, and any associated ureteric injury and its treatment were noted. Results Overall, 116 patients (median age 49 years, range 23–88 years) were referred for management of vesicovaginal fistula during the study period. Four of these patients (3.4%) had associated ureteric injury, one of whom had bilateral injury. Ureteric obstruction alone was noted in two patients, ureterovaginal fistula alone in one patient, and bilateral ureteric obstruction and ureterovaginal fistula in one patient. All ureteric injuries were managed with simultaneous reimplantation into the bladder at the time of vesicovaginal fistula repair. Five patients had post‐radiotherapy vesicovaginal fistula, and the remainder were post‐surgical. Three patients with post‐radiotherapy vesicovaginal fistula proceeded to primary diversion. Conclusions Ureteric injury is far less common than previously reported, occurring in <5% of patients presenting with vesicovaginal fistula. It can be successfully managed, and it remains the major indication for abdominal repair of vesicovaginal fistula.