The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice

Objective: To determine whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by the concomitant administration of grapefruit juice. Methods: Six healthy volunteers were recruited for a balanced cross-over study. Each volunteer received 120 mg terfenadine 30 min after drinking 300 ml of either water or freshly squeezed grapefruit juice. The alternative treatment was administered on the second study day 2 weeks later. Measurements of the area under the terfenadine plasma concentration-time curve (AUC), maximum terfenadine concentration (C_max) and the time to maximum concentration (t_max) were made, and the corrected QT (QTc) interval was measured from the surface electrocardiogram. Results: Terfenadine was quantifiable in plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC of terfenadine was significantly increased by concomitant grapefruit administration (median values 40.6 vs 16.3 ng · ml⁻¹ · h), as was the C_max (median values 7.2 vs 2.1 ng · ml⁻¹). The t_max was not significantly increased and there was no significant change in the median QTc interval despite the increased terfenadine levels. The 95% confidence interval for the difference in the change in QTc interval at C_max was −13 to +38 ms. Conclusion: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of time. Received: 14 October 1996 / Accepted in revised form: 10 December 1996     

Cyclosporine A inhibition of microcystin toxins

Cyclosporine A (CyA) given i.v. at a dose of 1.25 mg/mouse blocks a subsequent i.v. lethal dose (1.7-1.8 x LD50) of microcystin-LR for 24 hr, and is about 50% protective at 48 hr. Conversely, the fraction of mice that can be rescued by CyA (0.2 mg/mouse) after a lethal dose of microcystin-LR decreases rapidly with a pharmacodynamic half-time of only about 100 sec. The prophylactic action of CyA was tested against lethal doses of four microcystins. The acute lethality of 1.7-1.8 x LD50 dose of microcystin-LR, -RR, -LY, or -LA given 1 hr after administration of 0.2 mg of CyA is 0%, 0%, 58%, or 100%, respectively. Even a 0.6 mg/mouse dose of CyA is ineffective prophylaxis against a lethal dose of microcystin-LA. The inhibitory potency of CyA on microcystin toxicity can be completely reversed by the single L-amino acid substitution of alanine for arginine in the microcystin.     

Schultz metacarpophalangeal arthroplasty: a long-term follow-up study

We describe a prospective, long-term evaluation of the Schultz metacarpophalangeal joint implant. The prosthesis is a semiconstrained, cemented implant with a ball-in-socket articulation. Thirty-six implants were followed for an average of 10.9 years. There was a progressive decrease in range of motion and strength and a recurrence of ulnar deviation. The neck of the proximal phalangeal component fractured in 39% of the joints. Periarticular heterotopic bone formed in all joints, but was extensive in only 22%. Although some lucency of the bone-cement interface was seen in 80% of the joints, no prosthetic loosening occurred in this series. Our results indicate that long-term, intramedullary cement fixation of relatively long-stemmed components can be satisfactory. However, the articulated portion of this implant does not consistently withstand the stresses transmitted across the joint and does not provide long-term joint stability.     

Use of sterile gloves in the management of sutured hand wounds in the A&E department

In a single-blind, controlled, prospective trial of 242 sutured wounds of the hand in the A&E department there was increased late purulent infection in those treated without gloves. This difference is statistically significant. We recommend wearing of sterile gloves to suture all wounds in A&E departments.