Homocysteine-Lowering Therapy and Early Progression of Transplant Vasculopathy: A Prospective, Randomized, IVUS-Based Study

Although observational studies suggest that hyperhomocysteinemia may be a risk factor for coronary allograft vasculopathy (CAV), prospective data on homocysteine-lowering interventions and CAV development are lacking. We, therefore, randomized 44 de novo heart transplant (HT) recipients to 15 mg/day of 5-methyl-tetrahydrofolate (n=22), or standard therapy (control group, n=22) to investigate the effect of homocysteine lowering on the change in coronary intimal hyperplasia during the first 12 months after transplant, as detected by intra-vascular ultrasound (IVUS). Although 12 months after HT, homocysteinemia was lower in folate-treated patients (p<0.001), coronary intimal area increased similarly in the two groups (p>0.4). Conversely, hypercholesterolemia and cytomegalovirus infection were both associated with increased intimal hyperplasia (p<0.04), independently from folate intake. Sub-group analysis revealed that folate therapy reduced intimal hyperplasia in patients with hyperhomocysteinemia before randomization (n=19; p=0.02), but increased intimal hyperplasia in patients with normal homocysteine plasma concentrations (p=0.02). This bimodal effect of folate therapy persisted significantly after adjusting for cytomegalovirus infection and hypercholesterolemia. Despite effective in prevent hyperhomocysteinemia after heart transplantation, folate therapy does not seem to affect early CAV onset. However, sub-group analysis suggests that folate therapy may delay CAV development only in patients with baseline hyperhomocysteinemia, while may favor CAV progression in recipients with normal baseline homocysteinemia.     

Assessing the Stiffness of Spinal Fusion in Animal Models

The clinical goal of spinal fusion is to reduce motion and the associated pain. Therefore, measuring motion under loading is critical. The purpose of this study was to validate four-point bending as a means to mechanically evaluate simulated fusions in dog and rabbit spines. We hypothesized that this method would be more sensitive than manual palpation and would be able to distinguish unilateral vs bilateral fusion. Spines from four mixed breed dogs and four New Zealand white rabbits were used to simulate posterolateral fusion with polymethyl methacrylate as the fusion mass. We performed manual palpation and nondestructive mechanical testing in four-point bending in four planes of motion: flexion, extension, and right and left bending. This testing protocol was used for each specimen in three fusion modes: intact, unilateral, and bilateral fusion. Under manual palpation, all intact spines were rated as not fused, and all unilateral and bilateral simulated fusions were rated as fused. In four-point bending, dog spines were significantly stiffer after unilateral fusion compared with intact in all directions. Additionally, rabbit spines were stiffer in flexion and left bending after unilateral fusion. All specimens exhibited significant differences between intact and bilateral fusion except the rabbit in extension. For unilateral vs bilateral fusion, significant differences were present for right bending in the dog model and for flexion in the rabbit. Unilateral fusion can provide enough stability to constitute a fused grade by manual palpation but may not provide structural stiffness comparable to bilateral fusion.     

Reduction of scar formation in full-thickness wounds with topical celecoxib treatment

Adult wound repair occurs with an initial inflammatory response, reepithelialization, and the formation of a permanent scar. Although the inflammatory phase is often considered a necessity for successful adult wound healing, fetal healing studies have shown the ability to regenerate skin and to heal wounds in a scarless manner in the absence of inflammation. The cyclooxygenase-2 (COX-2) enzyme, a known mediator of inflammation, has been shown to contribute to a variety of inflammatory conditions and to the development of cancer in many organs. To examine the role of COX-2 in the wound healing process, incisional wounds were treated topically with the anti-inflammatory COX-2 inhibitor celecoxib. Acutely, celecoxib inhibited several parameters of inflammation in the wound site. This decrease in the early inflammatory phase of wound healing had a significant effect on later events in the wound healing process, namely a reduction in scar tissue formation, without disrupting reepithelialization or decreasing tensile strength. Our data suggest that in the absence of infection, adult wound healing is able to commence with decreased inflammation and that anti-inflammatory drugs may be used to improve the outcome of the repair process in the skin by limiting scar formation.     

SUICIDE ATTEMPT DUE TO METOCLOPRAMIDE-INDUCED AKATHISIA

Akathisia as a side-effect of metoclopramide has received increasing attention in consultation-liaison psychiatry in recent years. A case of metoclopramide-induced akathisia resulting in a suicide attempt is reported in order to highlight the suffering of such patients and the factors that lead to misdiagnosis.