Preloading magnesium attenuates cisplatin-associated nephrotoxicity: pilot randomized controlled trial (PRAGMATIC study).

BACKGROUND: Cisplatin is one of the most potent chemotherapeutic drugs used in head and neck cancer treatment; however, nephrotoxicity is the major side-effect limiting usage. Magnesium supplementation has been reported to reduce risk in non-controlled studies. We investigated whether preloading with magnesium prevents nephrotoxicity with a low-dose weekly cisplatin regimen. METHODS: We carried out a prospective pilot, single-blinded, randomized controlled trial to compare cisplatin-associated acute kidney injury (cis-AKI) and acute kidney disease (cis-AKD) between two groups: intravenous 0.9% NaCl 500 ml + KCL 20 mEq over 4 h pre-cisplatin 40 mg/m2 weekly for 7-8 weeks (control group) compared with additional 16 mEq magnesium added to the saline infusion (Mg group) in 30 head and neck cancer patients. Cis-AKI was defined as an increased serum creatinine (SCr) ≥ 0.3 mg/dl within 7 days and cis-AKD is an increased SCr ≥ 0.3 mg/dl between last SCr and baseline pre-chemotherapy SCr. RESULTS: The overall cisplatin tumor response rate and survival were comparable between groups. The baseline characteristics were comparable between groups, although SCr was lower in the controls (0.70 ± 0.17 versus 0.87 ± 0.17 mg/dl, P = 0.01). The incidence of cis-AKI was similar (4.6% versus 1.3%); however, the incidence of cis-AKD was higher for the control group (46.7% versus 6.7%, hazard ratio = 0.082, 95% confidence interval 0.008-0.79, P = 0.03). The time to develop cis-AKD was significantly shorter in the control group (P = 0.007). CONCLUSIONS: The magnesium-preloading regimen was safe and significantly showed a decreased incidence of cis-AKD. The encouraging results of our pilot study need to be confirmed in a large-scale randomized controlled trial.

Acute neurological presentation due to copper deficiency in a hemodialysis patient following gastric bypass surgery.

Acquired copper deficiency has been recently recognized as a cause of myelopathy, and has been reported to occur many years after gastric bypass surgery performed to aid weight reduction in morbidly obese patients. We report a case of a young woman treated by hemodialysis who presented with acute neurological symptoms 5 months after gastric bypass surgery for severe obesity. She had symptoms and signs of cerebellar, spinal cord and peripheral nerve disease, which improved following parenteral copper supplementation. Now that gastric bypass surgery is being offered to morbidly obese hemodialysis patients, this case highlights the importance of monitoring copper levels in hemodialysis patients following gastric bypass surgery.

Hemodialysis of chronic kidney failure patients requiring ablative radioiodine therapy.

Ablative radioiodine therapy is the standard treatment for thyroid carcinoma, but as (131)I is predominantly cleared by renal excretion, its clearance will be reduced in patients with chronic kidney disease, particularly in anuric patients on dialysis. The high dose of radioactivity used in the procedure results in an increased risk of radioactive exposure to the patient, the dialysis staff, and the machinery. Here, we describe how to successfully hemodialyze patients with chronic kidney failure requiring ablative (131)I therapy for thyroid cancer while minimizing risks to the patient and dialysis staff. With appropriate training, hemodialysis treatments can be safely delivered to patients receiving radiotherapy.

Fragment based drug discovery using fluorescence correlation: spectroscopy techniques: challenges and solutions.

Novel starting points for medicinal chemistry programmes can be effectively identified by screening libraries of fragment molecules in biochemical assays at high concentration. The key to success with this approach is the combination of a high quality fragment library with sensitive biochemical screening methods. There are an increasing number of literature reports where weakly active fragment molecules have been identified by high concentration biochemical assays. We have successfully demonstrated the use of high concentration screening of fragments, using a portfolio of single-molecule Fluorescence Correlation Spectroscopy (FCS+plus) detection techniques to ensure the highest reproducibility and sensitivity, and have determined the binding mode of active fragments to target proteins by X-ray crystallography. Further biophysical detection methods are reviewed for their applicability to studies of fragment binding.