Acyclovir-induced acute renal failure and the importance of an expanding waist line.

A 23-year-old gentleman with no significant medical history other than obesity was admitted with a history of balance problems, double vision and strange behaviour following a fall from bed. Systems examination was unremarkable. The patient was given intravenous acyclovir and intravenous ceftriaxone given the suspicion of encephalitis/meningitis. Investigations including routine bloods, CT/MRI Head and lumbar puncture were unremarkable. Within 48 h of commencing intravenous acyclovir, there was a marked deterioration in renal function. On stopping acyclovir therapy, renal function improved back to baseline. No other cause for deterioration in renal function was identified. The most likely cause for acute renal failure was secondary to acyclovir therapy. This has been well documented and is due to intratubular crystal precipitation. Moreover, in this case nephrotoxicity is likely secondary to the large boluses of intravenous acyclovir that had been given as prescribed according to the total body weight.

Apparent renal disease due to elevated creatinine levels associated with the use of boldenone.

The widespread use of reporting estimated glomerular filtration rate (eGFR) alongside serum creatinine has led to a heightened appreciation of renal disease. However, creatinine is recognized as an insensitive marker of true GFR and therefore can lead to misdiagnosis of renal dysfunction in the absence of true pathology. We report the case of a 37-year-old male referred due to abnormal eGFR and creatinine in the absence of clinical signs, symptoms or other biochemical abnormalities of renal disease. Subsequent investigations based on a high index of suspicion for exogenous substance abuse led to a novel observation of significantly raised creatinine due to the presence of boldenone, an equine anabolic steroid commonly abused in body building.

Successful outcome of accidental ethylene glycol poisoning despite delayed presentation.

A 69-year-old man presented to the emergency department after being found unconscious by his son. He had experienced headache the previous day but had been otherwise well. Investigations revealed a severe metabolic acidosis, raised lactate and acute kidney injury. The calculated anion and osmolar gap were both elevated at 37.7 and 39.3, respectively. Due to his reduced Glasgow coma score (GCS) he was intubated and a CT scan performed: only a small, mature pontine infarct was found of uncertain significance. Further questioning of the family revealed accidental ingestion of 150 ml of a 'blue liquid' 24 h earlier (later identified as car screenwash). With ethylene glycol (EG) poisoning suspected, he was given intravenous ethanol, fomepizole (a competitive inhibitor of alcohol dehydrogenase) and haemofiltration. Despite the delayed presentation, prompt recognition and treatment of EG poisoning led to a successful discharge in this case.

Trisodium citrate 46.7% selectively and safely reduces staphylococcal catheter-related bacteraemia.

BACKGROUND: Trisodium citrate (TSC) 30% has been shown in a randomized control trial to be an effective antimicrobial catheter locking solution, able to significantly reduce catheter-related bacteraemia (CRB) in haemodialysis patients. Since that report, the formulation in Europe has been changed to 46.7% TSC without confirmatory data on efficacy. We report a 55 915 patient-day at risk experience in tunnelled lines of 46.7% TSC, emphasizing efficacy and changes in microbiology seen. METHODS: On 1 July 2006, inter-dialytic catheter locking solution was changed from 5000 IU/ml heparin to Citra-lock(TM) (46.7% TSC) in all haemodialysis patients at Barts and the London Renal Unit dialysing through an incident or prevalent tunnelled catheter. Prospectively collected blood culture data for the 6 months prior to the switch and 3 months at the end of the first year of TSC use were analysed. TSC tolerability was excellent with only a single withdrawal for intolerance of the agent. No major adverse events were reported. RESULTS: A major fall in CRB rates was noticed with a change from heparin (2.13/1000 catheter-days) in 2006 to TSC (0.81/1000 catheter-days) in 2007. This was due to significant reductions in staphylococcal CRB, true for sensitive, methicillin-resistant and coagulase-negative staphylococci. No increase in catheter malfunction was observed. CONCLUSIONS: We found that 46.7% TSC is a safe, convenient and highly effective catheter locking solution, leading to significant reduction in CRB largely by preventing staphylococcal bloodstream infections. Given that Staphylococcus aureus in particular is associated with serious and often disseminated infection, TSC seems to be a powerful tool for dialysis units.

Aromatase inhibition by 15-deoxy-prostaglandin J(2) (15-dPGJ(2)) and N-(4-hydroxyphenyl)-retinamide (4HPR) is associated with enhanced ceramide production.

Inhibition of aromatase activity is an established endocrine therapy in the treatment of hormone-dependent breast cancer. Recent studies on aromatase inhibition by the synthetic retinoid 4HPR, also known as fenretinide, and the PPARgamma agonist 15-dPGJ(2) have implicated a direct receptor-independent, redox-sensitive mechanism of action. The signalling molecule ceramide has also been previously implicated as a negative regulator of aromatase activity. In the present study, we have investigated a potential mediatory role for this sphingolipid during aromatase inhibition by fenretinide and 15-dPGJ(2) in the breast cancer cell line MDA MB 231 and JEG-3 choriocarcinoma cells. 4HPR and 15-dPGJ(2) caused a dose-dependent inhibition of aromatase activity associated with an increase in ceramide production. Both these actions were redox-sensitive as demonstrated by their abrogation in the presence of the anti-oxidant N-acetylcysteine. Exogenous ceramide analogue mimicked these inhibitory actions on aromatase, but in a redox-independent manner. Blockade of the de novo ceramide production pathway by fumonisin B(1) or myriocin inhibited the ceramide responses, but did not prevent aromatase inhibition by 15-dPGJ(2) or 4HPR. This study highlights a potential role for aromatase inhibition and the stress-response signal ceramide during the therapeutic actions of 15-dPGJ(2) and 4HPR in breast cancer treatment. However, these data do not support a mediatory role for this sphingolipid during aromatase inhibition by these agents.

Prostaglandin J2 metabolites inhibit aromatase activity by redox-sensitive mechanisms: potential implications for breast cancer therapy.

The mechanisms by which prostaglandin (PG)J(2) metabolites inhibit tumorigenicity are poorly understood but may involve thiol reactivity or peroxisome proliferator-activated receptor (PPAR)-dependent pathways. Because aromatase is an important therapeutic target in breast cancer treatment, we have investigated the effect of PGJ(2) metabolites on aromatase activity and evaluated a potential role for redox status during PGJ(2) metabolite action. 15-deoxy-Delta(12,14)PGJ(2) (15d-PGJ(2)) and 9-deoxy-Delta(9,12)13,14-dihydroPGD(2) (Delta(12)PGJ(2)) caused dose-dependent inhibition of both pre-induced aromatase activity in human breast fibroblasts and MDA MB 231 breast cancer cells and of constitutive aromatase activity in JEG-3 choriocarcinoma cells. Structure-activity studies showed that this inhibition was mimicked by 4-cyclopentene-1,3-dione but not by the PPARgamma agonist troglitazone nor the eicosanoids PGE(2) or arachidonic acid. The thiol oxidants diamide and H(2)O(2) simulated the inhibitory action of 15d-PGJ(2) on aromatase activity, whereas the glutathione (GSH) repletor and antioxidant N-acetyl-cysteine (NAC) reversed these actions of 15d-PGJ(2) and H(2)O(2) on aromatase. 15d-PGJ(2) also caused a direct dose-dependent inhibition of aromatase activity in JEG-3 cell sonicates, which was also reversed in the presence of GSH. Kinetic analysis of this 15d-PGJ(2)-induced inhibition of cell-free aromatase indicated the involvement of a non-competitive mechanism possibly resulting from direct thiol-targeted alkylation of the enzyme. These redox-sensitive, PPARgamma-independent actions of 15d-PGJ(2) on aromatase activity demonstrate a novel therapeutic potential for such cyclopentenone PGs in breast cancer treatment.