Treatment of severe acute lung allograft rejection with OKT3 and temporary extracorporeal membrane oxygenation bridging.

OBJECTIVES: The use of OKT3 for treatment of advanced high-grade acute rejection episodes eventually can result in cytokine release and consecutive pulmonary edema. Temporary extracorporeal membrane oxygenation (ECMO) bridging can be used to overcome this crucial period before the beneficial effects of OKT3 can be observed. METHODS: We summarize our experience with three patients, who underwent lung transplantation and presented with severe acute rejection episodes. OKT3 had to be initiated due to insufficient response to standard rejection therapy with corticosteroids. Upon initiation of OKT3 treatment, a massive life-threatening deterioration of lung function in spite of heavily invasive respirator treatment was seen and temporary ECMO support was imperative to support graft function. Results of this treatment were retrospectively reviewed. RESULTS: In all cases femoro-femoral veno-arterial ECMO was used for support of the impaired graft and after a period of 4-5 days led to a massive improvement of graft function. In the further course two patients could be discharged from hospital and are still alive 30 and 36 months, respectively, after the described incident. One patient died 4 months later due to liver failure. CONCLUSIONS: We conclude that the use of ECMO support in patients experiencing significant side effects from OKT3 therapy is a useful and effective therapeutic tool to overcome the initial critical period until the lung has sufficiently recovered.     

Characteristics of pollinosis caused by Betula in patients from Ourense (Galicia, Spain).

A retrospective study was performed to describe the features of the pollinosis caused by Betula in the area of Ourense, Spain. The pollen count was carried out with a Lanzoni volumetric Hirts spore trap (1993-2000). The Betula pollen represented 5% over the annual total (annual mean quantity: 965 grains). It was present in the air from March to mid-May. The highest peaks took place in April (maximum values mean: 131 grains/m3). The medical records of 222 patients (mean age 25.66 years) diagnosed with pollinosis (1998-2000), who lived at less than 30 km. from the spore trap, were reviewed. In all of them, the skin-prick test (SPT) was carried out with pollen allergens. The percentages of positive SPT were: Lolium perenne, 91.89% (16.6% monosensitized); Plantago lanceolata, 71.17% (1.26% monosensitized); Betula alba, 41.89% (10.75% monosensitized); Platanus hybrida, 34.95%; Olea europea, 10.36%; and Parietaria judaica, 6.3%. The mean age of Betula monosensitized patients was 44.7 years. The majority of them had symptoms in March-April, 40% had asthma symptoms, 80% had lived in Central Europe, and 30% of them presented an oral allergy syndrome to fruits. There were 41.93% of the patients with positive SPT to Betula pollen who had asthma symptoms, in comparison with 23.25% of the patients with negative SPT to Betula (p = 0.0034). There were 20.28% of the patients with positive SPT to Betula pollen, who had lived in Central Europe, in comparison with 4.27% of the patients with negative SPT to Betula, p: 0.00049. The relative risk of sensitization was 2.05. CONCLUSIONS: Betula pollen was the second cause of clinical pollinosis in our patients, after grass, being responsible of the symptoms in the early spring, in a small number of the patients in their forties. The presence of asthma was higher in Betula sensitized patients, and the residence in Central Europe was a sensitization risk factor.     

Pharmacology of the AC AT Inhibitor Avasimibe (CI‐1011)

Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration‐dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B‐containing lipoproteins into plasma. Avasimibe induced cholesterol 7α‐hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol‐fed as well as in non‐cholesterol‐fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non‐HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50–500 mg/day, significantly reduced plasma total triglyceride and VLDL‐cholesterol. Although total cholesterol, LDL‐cholesterol, and HDL‐cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol‐lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol.     

Nitric oxide mediates the neurogenic vasodilation of bovine cerebral arteries

Nitric oxide (NO) is a mediator of the vasodilation induced by a variety of physiological and pharmacological stimuli. The possible role of NO in the relaxation elicited in cerebral arteries by perivascular nerve stimulation has been investigated. Electrical field stimulation of precontracted bovine cerebral arteries induced a relaxation that was blocked by tetrodotoxin, but not by adrenergic or muscarinic receptor antagonists, suggesting the existence of noradrenergic, noncholinergic dilator nerves, as has been shown in other species. The relaxation was significantly reduced by the inhibitors of NO synthesis, NG-monomethyl-L-arginine and nitro-L-arginine methyl ester, but not by the enantiomer, NG-monomethyl-D-arginine. Such a reduction was reversed by L-arginine. In addition, transmural nerve stimulation (TNS)-induced relaxation was potentiated by superoxide dismutase. No response to TNS was observed in arteries without endothelium. These results suggested that neurogenic relaxation of bovine cerebral arteries is mediated by endothelium-derived NO.     

The unusual association of three autoimmune diseases in a patient with Noonan syndrome.

We report on a 26-year-old female affected by Noonan syndrome (NS), a congenital disorder characterized by various phenotypic features and congenital anomalies) associated with a variety of autoimmune diseases, including systemic lupus erythematosus, celiac disease, and Hashimoto thyroiditis. Autoimmunity is seldom described in NS and the association between this congenital disease and three autoimmune disorders has not been previously reported. Should the occurrence of autoimmune disorders in NS be confirmed, a relevant clinical and laboratory evaluation of NS patients should be performed in order to clarify whether the immune system involvement represents only an occasional event or is a feature of the disease.