Clinical adaptation of a high-performance liquid chromatographic method for the assay of pyridoxal 5'-phosphate in human plasma.

Vitamin B6, measured as pyridoxal 5'-phosphate (PLP), is a co-enzyme in the transsulfuration pathway of homocysteine metabolism. Since depletion of PLP has been suggested as an independent risk factor for coronary artery disease, PLP is frequently measured to guide patient care. By a change and utilization of an Aquasil C18 column and the addition of an acetonitrile clean-up gradient to the potassium phosphate, with sodium perchlorate and bisulfite buffer between samples we report the modification of a previously described method for analysis of PLP. The result is a more practical, efficient, reliable and robust method for daily clinical use. We also determined and report that it is critical to protect freshly prepared standard PLP samples from light exposure during assay preparation.

Proximal tubule cell response to radiographic contrast media.

Renal dysfunction associated with contrast media (CM) administration is generally attributed to reduced renal blood flow. Studies, however, also suggest direct tubular effects of CM, whose mechanisms remain unclear. This study was conducted to assess the chemotoxic effects of iopamidol, a prototypic CM, on a porcine proximal tubule (PT) cell line, LLC-PK(1) cells. Results indicate that iopamidol did not affect cell viability (determined by trypan blue exclusion and fluorescein staining), but did reduce cell proliferation. Moreover, iopamidol altered mitochondrial function, as determined by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and mitochondrial membrane potential. Decreased MTT reduction was evident with all CM tested, and its rapid recovery after CM removal suggests that inhibition of mitochondrial function is reversible. Injury to PT cells by iopamidol is supported by the fact that CM increase extracellular adenosine, an indicator of cellular stress. This study provides greater insight into the mechanism underlying the nephrotoxicity induced by contrast in patients and explains the reversibility of this toxicity.

If LDL-C is the answer...what was the question? What do the data really show?

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are frequently utilized in the treatment of hypercholesterolemia. With recently completed statin clinical cardiovascular outcomes data available, the purpose of this review is to analyze the relative benefits of each molecule and to determine whether "lower is better" is a correct hypothesis for secondary prevention. Twenty-one clinical studies, each with a duration of statin therapy of 6 months or longer, were reviewed, and the pharmacologic effects of these agents on cardiovascular outcomes was examined. As evaluated by study drug, statistical event reduction was achieved in seven of nine pravastatin studies, one of three simvastatin studies, one of six lovastatin studies, zero of two fluvastatin studies, and zero of one atorvastatin study. Pravastatin was the only statin proven statistically to reduce events in both primary and secondary prevention. Thus, all of the statins do not appear to be the same in terms of their ability to reduce cardiovascular events. Until head-to-head trials have been completed, these clinical outcomes data suggest that in patients with severe hypercholesterolemia who require high-dose statin therapy, simvastatin 80 mg each evening would appear to be the agent of choice. However, pravastatin 40 mg daily at bedtime appears to be a unique molecule, with the strongest evidence for event reduction in the majority of patients with moderate hypercholesterolemia with, or who are at risk for, coronary heart disease.

Oxygen free radicals and contrast nephropathy.

Ionic, high-osmolality contrast medium causes nephrotoxicity associated with increased intrarenal adenosine production. To test the hypothesis that oxygen free radicals (produced during intrarenal adenosine catabolism to xanthine) should be implicated in the pathogenesis of ionic, high-osmolality contrast medium nephrotoxicity in humans and to determine whether magnesium protects the kidney from oxygen free radical injury following contrast, 39 patients with mild renal dysfunction were divided into low (LoMg++) and normal (NlMg++) magnesium states and randomized to precoronary angiography oral allopurinol (a xanthine oxidase inhibitor) or placebo. Creatinine clearance and urinary xanthine excretion were measured before and after angiography. Forty-eight hours after contrast medium exposure, placebo-treated LoMg++ and NlMg++ patients had 61%+/-5% and 67%+/-6% increases in urinary xanthine excretion, respectively; however, placebo-treated LoMg++ patients had a greater (79%+/-9% v 35%+/-6%; P < 0.01) decrease in creatinine clearance than placebo-treated NlMg++ patients. Allopurinol-treated LoMg++ and NlMg++ patients had no significant change in urinary xanthine excretion, but did have 40%+/-7% and 33%+/-5% decreases, respectively, in creatinine clearance 48 hours after contrast medium exposure. There was no difference in renal dysfunctional response among placebo-treated NlMg++ patients or allopurinol-treated LoMg++ or NlMg++ patients. These data suggest (1) that oxygen free radicals contribute to ionic, high-osmolality contrast medium nephrotoxicity in hypomagnesemic patients with mild renal disease and (2) that magnesium attenuates the nephrotoxicity mediated by oxygen free radicals.

Experience with PICC at a university medical center.

A retrospective evaluation of the use of the peripherally inserted central catheters that were inserted by a small, credentialed nursing staff to provide ongoing venous access in the general adult and pediatric patient population at the University of Rochester Medical Center in Rochester, New York. Between 1993 and 1995, 602 catheters were inserted in 775 suitable patients. Correct catheter tip placement in the superior vena cava was achieved in 95% of placements with a catheter dwell time ranging from less than 1 day to 353 days (average, 24 days). Strict adherence to obtaining and monitoring quality assurance kept catheter complications to a minimum.