Nonsteroid antiinflammatory agents as a substitute treatment for steroids in ATGAM-treated cadaver kidney recipients

A nonsteroid antiinflammatory agent (Ibuprofen) was used in a controlled randomized study to determine its ability to replace steroids in the prophylaxis of cadaveric kidney rejection. Thirty-three cadaver kidney recipients were randomly assigned either to a control group (16 patients) receiving azathioprine, high doses of prednisolone, and antithymocyte globulin (ATGAM) for three months, or to an experimental group (17 patients) receiving azathioprine and ATGAM according to the same protocol, ibuprofen instead of steroids. The frequency of rejection was higher in the experimental group (2.18 episodes per patient) than in the control group (1.44 episodes per patient). Nevertheless, in the experimental group 5 patients had no early rejection episode, 60% of early rejections were totally reversible without steroids, and 3 patients never received steroids at all during the first year and had normal renal function and biopsies. Steroids had to be introduced in the treatment of 14 patients, but after an average period of 32.5 days after surgery OKT3+ cell level was higher in the experimental group than in the control group, but similar to the OKT3+ cell level of patients receiving conventional therapy without ATGAM. Whatever the type of treatment, an increase in the OKT4+/OKT8+ ratio was associated in most cases with increased serum creatinine values. Conversely, a decreased OKT4+/OKT8+ ratio associated with renal failure was found in cases showing biological evidence of cytomegalovirus infection.     

Coffee drinking and risk of preterm birth

OBJECTIVES: We analysed the association between coffee drinking before and during the three trimesters of pregnancy and the risk of preterm birth of babies normal for gestational age (NGA) or small for gestational age (SGA). METHODS: Case-control study conducted in University clinics of North Italy. Cases were 502 women who delivered at <37 weeks of gestation. The controls included 1966 women who gave birth at term (>or=37 weeks of gestation) to healthy infants on randomly selected days at the hospitals where cases had been identified. RESULTS: There was inverse association for coffee consumption in the third trimester of pregnancy in SGA cases compared to NGA (heterogeneity test between OR: chi1(2)=5.6811 P<0.05). In comparison with not drinkers, all the ORs of overall intake of caffeine were closed near the unity for both SGA and NGA preterm birth. CONCLUSION: Compared with no consumption, a low consumption of coffee during pregnancy may not have significant effects on preterm birth.     

A Fas agonist induces high levels of apoptosis in haematological malignancies

We developed and tested a potent hexameric Fas agonist, termed MegaFasL, for its cytotoxic effects on a panel of human haematopoietic malignant cells and healthy human haematopoietic progenitor cells (CD34+CD38low). Results demonstrated that MegaFasL induced apoptosis in cell lines and primary cells representing multiple myeloma (MM), acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and Burkitt's lymphoma. Cells from a chronic myeloid leukaemia (CML) line and from patients with chronic lymphocytic leukaemia (CLL) were resistant. Furthermore, CD34+CD38low progenitor cells were also resistant to MegaFasL. The data indicate that MegaFasL could be a highly efficient therapeutic agent ex vivo or potentially in vivo.     

Distribution and numbers of indoleamine cell bodies in the cat brainstem determined with Falck-Hillarp fluorescence histochemistry

Using the Falck-Hillarp method, the cat brainstem was found to contain approximately 60,000 indoleamine (IA) cells. Most of these (46,000 or 77%) are located within the raphe nuclei. Nissl-stained material demonstrated both medium- and small-sized perikarya in the raphe nuclei, and quantitation revealed that the IA cells comprise only part of the medium-sized cells. Thus, the raphe dorsalis holds about 24,000 IA cells representing some 70% of its medium-sized cells. Corresponding values were for raphe pallidus 8,000 IA cells (55%), raphe centralis superior 7,400 (35%), raphe magnus 2,400 (15%), raphe obscurus 2,300 (33%), linearis intermedius 2,100 (23%), and raphe pontis 280 (9%). A considerable number of IA cells (13,600, representing 23% of the total) were found in locations outside the raphe nuclei: in ventral brainstem as lateral extensions from the raphe, among the bundles of fasciculus longitudinalis medialis, in periventricular gray and adjacent tegmentum, mixing with the noradrenergic cells of the locus coeruleus complex, among the mesencephalic dopamine cells, and in the nucleus interpeduncularis.     

Regulatory T cells in the control of autoimmune diabetes: the case of the NOD mouse

Over the last few years, there has been a revival of the concept of suppressor/regulatory T cells being central players in the control of various immune responses, including autoimmune responses and immune response to transplants, tumors, and infectious agents. It appears that regulatory T cells are diverse in their phenotypes, antigen specificity, and modes of action. Here we summarize studies from various groups, including our own, demonstrating that specialized subsets of regulatory T cells are pivotal in the control of autoimmune diabetes as well shown by the compelling evidence accumulated using the non-obese diabetic (NOD) mouse model. We also provide a discussion of the evidence showing that some biological products (such as CD3-specific monoclonal antibodies) are representatives of a new category of immunotherapeutic agents endowed with unique capacities to promote immunological tolerance (an antigen-specific unresponsiveness in the absence of long-term generalized immunosuppression) through their ability to induce immunoregulatory T cells.     

Interphase fluorescence in situ hybridization on selected plasma cells is superior in the detection of cytogenetic aberrations in plasma cell dyscrasia

Interphase fluorescence in situ hybridization (FISH) detects nonrandom cytogenetic abnormalities in plasma cell (PC) dyscrasia according to PC burden. However, when performed on cultured whole bone marrow (BM), it often fails to detect these aberrations. We have compared this interphase FISH technique with FISH after PC purification or identification to detect recurrent aberrations. In this study, 235 BM samples were collected from patients with multiple myeloma (MM) or related PC disorders regardless of disease status. All samples were analyzed in parallel. Clonal abnormalities were detected in 34.9% of cultured samples compared with 71.0% PC selected samples (P < 0.001). Moreover, FISH on PCs allowed to detect more abnormalities per case (P < 0.001) and identified higher percentages of abnormal nuclei (P < 0.001). This study indicates that FISH on PCs is the preferred technique for routine cytogenetic investigation of MM. © 2010 Wiley‐Liss, Inc.