Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

BKV in Simultaneous Pancreas-Kidney Transplant Recipients: A Leading Cause of Renal Graft Loss in First 2 Years Post-Transplant

With the introduction of more potent immunosuppressive agents, rejection has decreased in simultaneous pancreas/kidney transplant (SPK) recipients. However, as a consequence, opportunistic infections have increased. The purpose of this report is to outline the course of SPK patients who developed polyomavirus-associated nephropathy (PVAN). A retrospective review of 146 consecutive SPK recipients from January 1, 1996 to December 31, 2002 was performed. Immunosuppression, rejection and development of PVAN were reviewed. Nine patients were identified. All received induction with either OKT3 or thymoglobulin. Immunosuppression included tacrolimus/cyclosporine, MMF/azathioprine and sirolimus/prednisone. Two patients were treated for kidney rejection prior to the diagnosis of PVAN. Time to diagnosis was an average of 359.3 days post-transplantation. Immunosuppression was decreased but five ultimately lost function. However, none developed pancreatic abnormalities as demonstrated by normal glucose and amylase. Two underwent renal retransplantation after PVAN diagnosis and both have normal kidney function. PVAN was the leading cause of renal loss in SPK patients in the first 2 years after transplantation and is a serious concern for SPK recipients. The pancreas, however, is spared from evidence of infection, and no pancreatic rejection occurred when immunosuppression was decreased.     

Orthodontic fine adjustment after vertical callus distraction of an ankylosed incisor using the floating bone concept.

The outcome of vertical callus distraction of a segment of tooth-supporting alveolar process might be functionally and esthetically unsatisfactory because of the unidirectional impact of intraoral distraction devices. In this case report, we describe how, with a shortened consolidation phase and application of the floating bone effect, the tooth-supporting osteotomy segment can be successfully aligned 3 dimensionally. We applied orthodontic force systems that went beyond the unidirectional vector preset by the mechanical properties of the distraction device.     

Molecular and signaling mechanisms of atherosclerosis in insulin resistance.

Although the prevalence of cardiovascular complications is increased in insulin-resistant individuals, the underlying causes of this link have been elusive. Recent work suggests that several intracellular signal transduction pathways are inappropriately activated by hyperinsulinemia, hyperglycemia, increased free fatty acids, dyslipidemia, various inflammatory cytokines and adipokines--factors that are increased in insulin resistance. Once activated, substantial cross talk occurs between these pathways, especially a self-reinforcing cascade of vascular inflammation and cell dysfunction, greatly increasing the risk and severity of atherosclerosis in the insulin-resistant individual. We review several key cell-signalling pathways, describe how they are activated in they insulin-resistant state and the damage they induce, and discusses possible therapeutic approaches to limit vascular damage.     

Regulation of mast cells by β-agonists

The human lung mast cell is known to be a critical effector cell in the mediation of asthma. Activation of the mast cell by allergens and other stimuli leads to the release and generation of a wide variety of autacoids that cause bronchoconstriction, promote inflammation, and may influence airway remodeling. Therefore, the stabilization of mast cells has obvious value in the prevention of asthma. Among the drugs used to treat asthma, only β-agonists are effective stabilizers of mast cells. Both short- and long-acting β-agonists are effective against mast cells, but there are differences between agonists regarding the extent of inhibitory activity attained. Consequently, the type of β-agonist prescribed influences the degree of mast cell stabilization possible. Despite the potential value of attenuating mast cell activity with β-agonists, this benefit may diminish with time because of the development of tolerance. Both short- and long-acting β-agonists can induce tolerance to mast cell stabilization, and generally, higher efficacy agonists tend to induce greater levels of tolerance; however, weaker agonists induce greater levels of tolerance than might be expected. Tolerance to the mast-cell-stabilizing effects of β-agonists may be an issue clinically, because this occurs more readily than tolerance to smooth muscle relaxation. This could lead to a situation in which β-agonists fail to prevent the release of mediators from mast cells but can still effectively relax airway smooth muscle. The continued ability to bronchodilate could mask the unfavorable consequences of unchecked mediator release from mast cells.