ABSTRACT
Pulmonary thromboendartectomy (PTE) for chronic thromboembolic pulmonary hypertension may be complicated by reperfusion lung injury. This has previously been demonstrated to be neutrophil-mediated. We postulated that blocking selectin-mediated adhesion of neutrophils to the endothelium with Cylexin (CY-1503) would prevent reperfusion lung injury in this patient population. In this double-blind, randomized, placebo-controlled, parallel study, 26 patients received Cylexin the day of surgery and 25 received placebo. Significantly fewer patients in the treated group (31%) compared with the placebo group (60%) developed lung injury (p = 0.036). However, the average number of days of mechanical ventilation, days in the intensive care unit (ICU) and hospital, as well as mortality were not significantly different between the treatment groups. Those with reperfusion lung injury had significantly elevated percent neutrophils, total protein, and soluble P-selectin in bronchoalveolar lavage fluid compared with those without lung injury. We conclude that reperfusion lung injury after PTE is a high-permeability lung injury and its incidence can be reduced by the administration of Cylexin on the day of surgery.
Subject(s)
Endarterectomy/adverse effects , Lewis Blood Group Antigens/therapeutic use , Oligosaccharides/therapeutic use , Pulmonary Embolism/surgery , Reperfusion Injury/etiology , Reperfusion Injury/prevention & control , Adult , Aged , Bronchoalveolar Lavage Fluid , Double-Blind Method , Female , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/surgery , Male , Middle Aged , Pulmonary Embolism/complicationsABSTRACT
As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized with a Lewis(y) pentasaccharide (Le(y))-keyhole limpet hemocyanin (KLH)-conjugate vaccine together with the immunological adjuvant QS-21. Four different doses of the vaccine, containing 3, 10, 30, and 60 microg of carbohydrate were administered s.c. at 0, 1, 2, 3, 7, and 19 weeks to groups of 6 patients. Sera taken from the patients at regular intervals were assayed by ELISA for reactivity with naturally occurring forms of Le(y) (Le(y)-ceramide and Le(y) mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le(y)-expressing tumor cells. The majority of the patients (16/24) produced anti-Le(y) antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity related to the vaccine was observed. On the basis of this study, Le(y)-KLH should be a suitable component for a polyvalent vaccine under consideration for the therapy of epithelial cancers.
