Immunotoxicity profile of natalizumab.

Natalizumab is a monoclonal antibody to human alpha4 integrin indicated for treatment of multiple sclerosis and Crohn's disease that prevents extravasation of leukocytes into surrounding tissues and their involvement in inflammation. Because alpha4 integrins and their receptors are involved in hematopoiesis and immune cell trafficking, natalizumab may interfere with these processes. We evaluated the effects of natalizumab on immune function in monkeys using in vitro and in vivo studies. Consistent with the pharmacologic effects of natalizumab, dose-related increases in white blood cell counts and spleen weights were observed. Administration to monkeys did not result in statistically significant alterations in the percentages of circulating B-cells, T-cells, T-cell subsets (CD4, CD8), or stem cells (CD34). A modest and highly variable delay in the primary humoral response to T-cell-dependent antigens was observed. Ex vivo studies using cells from natalizumab-treated monkeys demonstrated that treatment did not alter immune regulatory or effector cell functions in blood lymphocytes or spleen cells. A similar lack of effect on these functions was observed in vitro following treatment of PBMC and monocytes from human donors. Overall, natalizumab was well tolerated in monkeys, demonstrated the expected pharmacologic effect on cell trafficking, and showed no adverse effect on immune cell function.

SCH 412499: biodistribution and safety of an adenovirus containing P21(WAF-1/CIP-1) following subconjunctival injection in Cynomolgus monkeys.

Monkey studies were conducted for the preclinical safety assessment of SCH 412499, an adenovirus encoding p21, administered by subconjunctival injection prior to trabeculectomy for postoperative maintenance of the surgical opening. Biodistribution of SCH 412499 was minimal and there was no systemic toxicity. Findings included swollen, partially closed or shut eye(s) and transient congestion in the conjunctiva. A mononuclear cell infiltrate was present in the conjunctiva, choroid and other ocular tissues, but completely or partially resolved over time. Electroretinograms and visual evoked potentials revealed no adverse findings. Thus, the findings are not expected to preclude the clinical investigation of SCH 412499.

Perioperative care of patients undergoing bariatric surgery.

The epidemic of obesity in developed countries has resulted in patients with extreme (class III) obesity undergoing the full breadth of medical and surgical procedures. The popularity of bariatric surgery in the treatment of extreme obesity has raised awareness of the unique considerations in the care of this patient population. Minimizing the risk of perioperative complications that contribute to morbidity and mortality requires input from several clinical disciplines and begins with the preoperative assessment of the patient. Airway management, intravenous fluid administration, physiologic responses to pneumoperitoneum during laparoscopic procedures, and the risk of thrombotic complications and peripheral nerve injuries in extremely obese patients are among the factors that present special intraoperative challenges that affect postoperative recovery of the bariatric patient. Early recognition of perioperative complications and education of the patient regarding postoperative issues, including nutrition and vitamin supplementation therapy, can improve patient outcomes. A suitable physical environment and appropriate nursing and dietetic support provide a safe and dignified hospital experience. This article reviews the multidisciplinary management of extremely obese patients who undergo bariatric surgery at the Mayo Clinic.