Background-Pulmonary arterial hypertension (PAH) in patients with sleep apnoea syndrome (SAS) is classically ascribed to associated chronic obstructive pulmonary disease (COPD). The aim of this retrospective study was to evaluate the possible occurrence of PAH as a complication of SAS in patients without COPD. Methods-Right

Patients with cystic fibrosis who have end-stage respiratory failure and associated liver cirrhosis have been considered poor candidates for lung transplantation because of high morbidity and mortality resulting from hepatic insufficiency after the operation. Since April 1989, our policy has been to combine heart-lung or lung and liver transplantation in this group of patients. Between June 1990 and March 1995, among 25 patients accepted in the program for combined transplantation, nine died awaiting transplantation and 10 underwent one of the following procedures: heart-lung-liver transplantation (n = 5), en bloc double lung-liver transplantation (n = 1), sequential double lung-liver transplantation (n = 3), and bilateral lobar lung transplantation from a split left lung and reduced liver transplantation (n = 1). There were 5 male and 5 female patients. The ages of the recipients ranged from 10 to 24 years. Mean forced expiratory volume in 1 second was 29% and mean forced vital capacity was 35% of predicted values. All patients were infected with resistant Pseudomonas, three with Pseudomonas cepaceia, and two patients had Aspergillus species in addition. All patients had severe cirrhosis with portal hypertension. Four patients had a history of esophageal variceal bleeding and two had had previous portosystemic shunts. The operation was performed as a two-stage procedure, the intrathoracic operation being completed before the abdominal stage was begun. Cardiopulmonary bypass was used in all patients because of poor clinical condition. Immunosuppression consisted of azathioprine, cyclosporine, and prednisone, as for isolated lung transplantation. There were two perioperative deaths, one caused by primary liver failure and the second by early lung dysfunction. For the first 3 months after transplantation pulmonary infection was the most common cause of morbidity. Other complications included tracheal stenosis (n = 1), bronchial stenosis (n = 1), biliary stricture (n = 2), and severe ascites (n = 3). All were successfully treated. Obliterative bronchiolitis developed in three patients. This was stabilized with FK 506 in two patients; the other patient underwent retransplantation at 38 months but eventually died of bleeding. Actuarial survival was 70% at 1 year and remained unchanged at 3 years. Significant functional improvement was observed in all survivors. For patients who have chronic respiratory failure with advanced cirrhosis, lung transplantation combined with liver transplantation can be performed with a satisfactory outcome.

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD. (Blood. 2001;97: 1590-1597)

Thrombosis and disseminated intravascular coagulation are common complications of cancer. Specific conditions associated with cancer such as stasis due to immobilization or blood flow obstruction, surgery, infections, endothelium damage due to chemotherapeutic agents and abnormalities of blood coagulation contribute to the hypercoagulable and thrombophilic state of cancer patients. This procoagulant state in cancer arises mostly from the capacity of tumor cells to express and release procoagulant activities (cancer procoagulant and tissue factor). Decreased levels of inhibitors of coagulation, impaired fibrinolysis, the presence of antiphospholipid antibodies and an acquired activated protein C resistance contribute to the hypercoagulable state. The activation of coagulation is also implicated in tumor proliferation through interactions of coagulation with inflammation and increased tissue factor pathway inhibitor. Laboratory diagnosis of the thrombophilic state include (1) elevation of clotting factors, fibrinogen/fibrin degradation products, hyperfibrinogenemia and thrombocytosis and (2) elevation of specific markers of activation of coagulation: fibrinopeptide A, fragment 1 + 2, thrombin-antithrombin complexes and D-dimers. However, none of the tests has any predictive value for the occurrence of thrombotic events in one individual patient. In patients with venous thromboembolism a noninvasive screening for occult cancer is able to detect a relatively high incidence of hidden cancer and the search for thrombophilia seems important in patients without known cancer.