Renal safety and pharmacokinetics of ibandronate in multiple myeloma patients with or without impaired renal function.

In this open-label study, the authors assessed the pharmacokinetics and safety of ibandronate in patients with multiple myeloma and varying renal function. Renal deterioration was graded at baseline depending on creatinine clearance in 4 stages (0: >80; 1: 50-79; 2: 30-49, and 3: <30 mL/min). Patients (n = 40) received intravenous ibandronate 6 mg (30-minute infusion). Ibandronate excretion and serum levels were measured over 24 hours. Serum creatinine, creatinine clearance, and markers of tubular damage were monitored before ibandronate infusion and at 24 and 72 hours following ibandronate infusion. Ibandronate clearance, AUC(0-24), AUC(0-infinity), serum t((1/2)), and C(max) were calculated. There was a significant positive correlation between ibandronate clearance and creatinine clearance (r = 0.858; P < .00001). The AUC for grade 3 renal insufficiency increased by approximately 60% versus grade 0 (P < .01) but was not significantly different between other grades of renal function. The t((1/2)) did not increase significantly, and peak serum levels of ibandronate were similar for the 4 grades of renal function. Serum creatinine, creatinine clearance, and markers of tubular damage did not change significantly within 72 hours of ibandronate infusion. Despite renal function already being compromised in this patient group, there was no evidence of acute nephrotoxicity with ibandronate.

Investigations of ascorbic acid interference in urine test strips.

Ascorbic acid at higher concentration in urine samples can lead to false negative results in a number of urine tests, with a potential risk of clinical findings being overlooked, particularly with glucose and hemoglobin. For this reason, the ascorbic acid status of urine samples should always be routinely known so as to establish what adjustment needs to be made. A much better approach, however, is to use a test which is by design largely resistant to ascorbic acid. We compared five very common 10-parameter urine test strips from different manufacturers. The results of this study show that of the strips tested, only the product Combur-Test from Roche Diagnostics is largely resistant to ascorbic acid interference. Even lowest - but clinically relevant - concentrations of erythrocytes (10/microL), hemoglobin (0.03 mg/dL), and glucose (50 mg/dL) were correctly detected with concentrations of up to 400 mg/L ascorbic acid. Higher analyte concentrations correctly reacted positive even in the presence of up to 1000 mg/L ascorbic acid.

G(-30)A polymorphism in the pancreatic promoter of the glucokinase gene associated with angiographic coronary artery disease and type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of coronary artery disease (CAD). A G(-30)A polymorphism in the beta-cell-specific promoter of glucokinase (GK-30PM) has been implicated in reduced pancreatic beta-cell function. Its impact on CAD has not been examined. METHODS AND RESULTS: The glucokinase G(-30)A variant was determined in 2567 patients with angiographic CAD and in 731 individuals in whom CAD had been ruled out by angiography. In carriers of the A allele, the adjusted OR of CAD was 1.39 (95% CI, 1.15 to 1.70). Corresponding ORs were 1.27 (95% CI, 1.02 to 1.59) and 1.92 (95% CI, 1.26 to 2.93) in individuals without and with T2DM, respectively. The prevalence of the A allele increased in parallel with the Friesinger coronary score. Patients with T2DM were more frequent among carriers of > or =1 A allele (OR, 1.17; 95% CI, 1.00 to 1.28). This association was stronger if CAD patients only were considered. The A allele was associated with higher glucose (fasting, P=0.002; 2 hours after oral glucose, P=0.017) and glycohemoglobin (HbA1c; P=0.002). Furthermore, presence of 1 A allele was negatively related to beta-cell function, estimated by beta percent (P=0.012) and by the ratios of proinsulin to insulin (P=0.025) and proinsulin to C peptide (P=0.019). CONCLUSIONS: The A allele of the pancreatic promoter of glucokinase increases the risk of CAD in individuals with and without T2DM. Furthermore, at least in CAD, it is associated with an augmented prevalence of T2DM.

Volume replacement with HES 130/0.4 may reduce the inflammatory response in patients undergoing major abdominal surgery.

PURPOSE: To investigate the effects of intravascular volume replacement therapy on the inflammatory response during major surgery. METHODS: Thirty-six patients scheduled for elective abdominal surgery were randomized to receive either 6% hydroxyethylstarch (130,000 Dalton mean molecular weight, degree of substitution 0.4; n = 18, HES-group) or lactated Ringer's solution (RL-group; n = 18) for intravascular volume replacement. Fluid therapy was given perioperatively and continued for 48 hr in the intensive care unit. Volume replacement was guided by physiological parameters. Serum concentrations of interleukin (IL)-6, IL-8 and IL-10 and soluble adhesion molecules (sELAM-1 and sICAM-1) were measured after induction of anesthesia, four hours after the end of surgery, as well as 24 hr and 48 hr postoperatively. RESULTS: Biometric and perioperative data, hemodynamics and oxygenation were similar between groups. On average, 4470 +/- 340 mL of HES 130/0.4 per patient were administered in the HES-group compared to 14310 +/- 750 mL of RL in the RL-group during the study period. Release of pro-inflammatory cytokines IL-6 and IL-8 was significantly lower in the HES-group [(peak values) 47.8 +/- 12.1 pg*dL(-1) of IL-6 and 35.8 +/- 11.2 pg*mL(-1) of IL-8 (HES-group) vs 61.2 +/- 11.2 pg*dL(-1) of IL-6 and 57.9 +/- 9.7 pg*mL(-1) of IL-8 (RL-group); P < 0.05]. Serum concentrations of sICAM-1 were significantly higher in the RL-group [(peak values) 1007 +/- 152 ng*mL(-1) (RL-group) vs 687 +/- 122 ng*mL(-1), (HES group); P < 0.05)]. Values of sELAM-1 were similar in both groups. CONCLUSION: Intravascular volume replacement with HES 130/0.4 may reduce the inflammatory response in patients undergoing major surgery compared to a crystalloid-based volume therapy. We hypothesize that this is most likely due to an improved microcirculation with reduced endothelial activation and less endothelial damage.

The impact of intensive serial plasmapheresis and iron supplementation on iron metabolism and Hb concentration in menstruating women: a prospective randomized placebo-controlled double-blind study.

BACKGROUND: Iron (Fe) depletion is common among regular whole-blood donors, but can be prevented through regular oral Fe supplementation. Little is known, however, about the Fe metabolism of donors undergoing intensive plasmapheresis. These donors lose considerable amounts of blood drawn for laboratory analyses and remaining in the disposable plastic sets. STUDY DESIGN AND METHODS: Menstruating women were enrolled in a prospective placebo- controlled double-blind study. One hundred women were randomly allocated to receive either 100 mg of elemental Fe per day or placebo over 24 weeks and asked to donate plasma at 1-week intervals. Hb was determined before each plasmapheresis. Ferritin, transferrin, and Fe concentration and reticulocyte count were measured every 4 weeks. RESULTS: Thirty donors in the placebo group and 29 receiving Fe completed the study. The total mean blood loss was 526 mL in the placebo group and 546 mL in the Fe arm (p=0.271). The number of donations with Hb values lower than 12.5 g per dL requiring prolongation of the time interval until the next plasmapheresis was significantly greater in the placebo arm. In the placebo group (n=30), ferritin levels began to decline significantly 4 weeks after entry. When the study was completed, Hb concentration and reticulocyte count also were found to be significantly lower in the placebo group than in the Fe study arm (p=0.028 and p=0.036, respectively). Hb, ferritin, and transferrin levels and reticulocyte counts did not change significantly in the Fe group during the observation period. CONCLUSION: Menstruating women undergoing regular plasmapheresis at short intervals are prone to develop Fe depletion. This can be prevented by regular Fe intake. Laboratory analyses in product plasma instead of serum gained from whole-blood samples could be an alternative to reduce blood loss.