Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker.

Induction therapy is used in kidney transplantation to inhibit the activation of donor-reactive T cells which are detrimental to transplant outcomes. The choice of induction therapy is decided based on perceived immunological risk rather than by direct measurement of donor T-cell reactivity. We hypothesized that immune cellular alloreactivity pretransplantation can be quantified and that blocking versus depleting therapies have differential effects on the level of donor and third-party cellular alloreactivity. We studied 31 kidney transplant recipients treated with either antithymocyte globulin (ATG) or an IL-2 receptor blocker. We tested pre- and posttransplant peripheral blood cells by flow cytometry to characterize T-cell populations and by IFN-γ ELISPOT assays to assess the level of cellular alloreactivity. CD8(+) T cells were more resistant to depletion by ATG than CD4(+) T cells. Posttransplantation, frequencies of donor-reactive T cells were markedly decreased in the ATG-treated group but not in the IL-2 receptor blocker group, whereas the frequencies of third-party alloreactivity remained nearly equivalent. In conclusion, when ATG is used, marked and prolonged donor hyporesponsiveness with minimal effects on nondonor responses is observed. In contrast, induction with the IL-2 receptor blocker is less effective at diminishing donor T-cell reactivity.

Monoclonal gammopathy associated with multiple myeloma and visceral leishmaniasis in the dog: a comparison of two cases.

The term monoclonal gammopathy (MG) suggests the presence of clonal immunoglobulins in blood serum that are recognized as narrow spikes in the beta and/or gamma region of the electrophoretic pattern of serum. In the dog, MG is rare and is associated with a heterogeneous group of diseases that include multiple myeloma (the most common source of MG) as well as infectious and chronic inflammatory diseases such as Leishmaniasis. In this paper, two cases of MG are described: the first case is associated with multiple myeloma of monoclonal component type IgA/lambda, with the latter rare in dogs, and the second case involves MG that developed 3 years after an initial diagnosis of Leishmaniasis.

Primed CD8(+) T-cell responses to allogeneic endothelial cells are controlled by local complement activation.

CD8 T cells primed by transplantation recognize allogeneic class I MHC molecules expressed on graft vascular endothelium and contribute to allograft injury. We previously showed that immune cell-derived complement activation fragments are integral to T cell activation/expansion. Herein we tested the impact of local complement production/activation on T cell/endothelial cell (EC) interactions. We found that proinflammatory cytokines upregulated alternative pathway complement production by ECs, yielding C5a. We further found that ECs deficient in the cell surface C3/C5 convertase regulator decay accelerating factor (DAF, CD55) induced greater CD8 T-cell proliferation and more IFNgamma(+) and perforin(+) effector cells than wild-type (WT) ECs. Allogeneic C3(-/-) EC induced little or no CD8 responses. Abrogation of responses following C5a receptor (C5aR) blockade, or augmentation following addition of recombinant C5a demonstrated that the effects were mediated through T-cell-expressed-C5aR interactions. Analyses of in vivo CD8 cell responses to transplanted heart grafts deficient in EC DAF showed similar augmentation. The findings reveal that EC-derived complement triggers secondary CD8 T-cell differentiation and expansion and argue that targeting complement and/or C5aR could limit T-cell-mediated graft injury.

Communication of information to patients with inflammatory bowel disease: A European Collaborative Study in a multinational prospective inception cohort.

BACKGROUND AND AIMS: Communication to patients of information about their disease has become increasingly important in modern medicine, and particularly with chronic nonfatal disorders like inflammatory bowel disease (IBD), but the subject is not adequately researched or understood. METHODS: We studied the media and preferences for communication of information in a multi-national community-based inception cohort of European and Israeli patients with IBD and 10 years follow-up, using structured questionnaires categorizing demographics, disease status, current and preferred sources of information, use of electronic media, role of patients' associations, and satisfaction level. RESULTS: The 917 patients completing the questionnaire were derived from northern (60%) and southern (40%) countries. The mean age was 48.3 years (62% under 50 years); 51% were males; 67% had ulcerative colitis, 33% Crohn's disease. Sixty-six percent of patients designated the specialist as their primary source of information, 77% indicated satisfaction with their current information, and 65% reported not receiving information about medical treatment in the past year. Patient concerns were about new research into their illness (64%), medical treatments (58%), risks and complications (51%) and genetics (42%). Preferred sources of information were paper bulletin (76%), electronic media (30%) and international organization (79%). Diagnosis (ulcerative colitis or Crohn's disease), gender, education level and country impacted significantly on patients' choices. CONCLUSIONS: In providing health care information to patients with IBD their individual attitudes and preferences must be considered. There should be greater roles for IBD patients' associations and international IBD-research organizations, and an increasing use of electronic media.

[Vaginal microscopic evidence in women with symptoms of genital infection]. / Reperti microscopici vaginali in donne con sintomi di infezione genitale.

PIP: Vaginal living organisms have been defined as the most complete in human ecology. As many as 100 million colonies of microorganisms can live in a single ml of vaginal liquid. More common are the anaerobic types, particularly the lactobacillus and bacteroides. The low pH of the vagina, normally 4, is due to the high lactic acid content of the lactobacillus. Pathogenic bacteria is inhibited at 4.5 pH. Conversely, it proliferates at a high pH. The slightest alteration of this delicate equilibrium allows potentially pathogenic bacteria to grow to a concentration high enough to produce symptoms. Researchers have sought to identify new pathological microorganisms, due to the increase in reported cases of vaginal infection in recent years. New strains such as microplasmas and chlamydia are assuming greater importance. Evidence of the numerous vaginal microbes comes from anamnestic, symptomatological data and from simple laboratory tests conducted in gynecological clinics with microscopes and Gram coloration. 663 women were examined in 6 laboratories. The computerized data revealed that only 29, or 4.37%, showed no symptoms at all and had gone to the lab for a mere check up; 175, or 26.40%, complained of pain, burning and itching; 361, or 54.45%, revealed symptoms associated with leukorrhea; 98, or 14.78%, showed only leukorrhea. The epidemiological study shows the importance of candida albicans in the infectious pathology of the female genital organ. Trichomonas vaginalis and grambacteria infection have been detected particularly when an IUD is used. The negative result of numerous bacterioscopic exams has shown the necessity of more in-depth study of genital infections, using analytical cultural methodology.^ieng

[Morphologic and functional aspects of left ventricular hypertrophy evaluated by computerized echocardiography]. / Aspetti morfologici e funzionali dell'ipertrofia ventricolare sinistra, valutati attraverso la lettura computerizzata dei tracciati ecocardiografici.

We have investigated the possible echocardiographic progression of left ventricular (LV) hypertrophy, in different stages of primary hypertension. Both morphological (LV mass and ratio of interventricular septal thickness to posterior wall thickness-IVST/PWT-, in M-mode) and functional data (parietal stress, duration, degree and velocity of filling in the four phases of diastole, obtained through computerised interpretation of M-mode tracings), were examined. We also tried to assess the morphofunctional differences between LV hypertrophy secondary to primary hypertension and LV hypertrophy secondary to renovascular hypertension, hypertrophic obstructive cardiomyopathy and physical training. Patients with primary hypertension were further subdivided in three groups: A) 14 patients with hypertension of less than one year's duration, B) 28 patients with long-lasting hypertension, and C) 5 patients with cardiomegaly. There was a progressive increase from controls to Group C patients of left ventricular mass (controls 171 +/- 25; Group A 168 +/- 72; Group B 253 +/- 83; Group C 439 +/- 117) and septal hypertrophy (controls IVST/PVT 1 +/- 0.1; Group A 1.2 +/- 0.2; Group B 1.4 +/- 0.3; Group C 1.5 +/- 0.1). The isovolumic relaxation period was prolonged only in Group C (controls 8.6 +/- 3.5 per cent of the diastole; Group C 15 +/- 3.5%) LV dimensions during slow filling and atrial contraction as well as filling velocity during this latter phase of the cardiac cycle were increased in Group A (7.8 +/- 2.3 and 7.3 +/- 2%; 1.2 +/- 0.6 cm/cm X sec respectively) and B (10 +/- 6 and 10.8 +/- 4%; 1.2 +/- 0.6 cm/cm X sec) compared to the controls (5 +/- 2.8 and 3.7 +/- 2%; 0.7 +/- 0.2 cm/cm X sec). The Vcf max was not significantly different in the three groups. The patients with renovascular hypertension (N = 14) could be differentiated from those with primary hypertension of Group B for a greater increase in LV mass, with concentric hypertrophy (IVST/PWT = 1.2 +/- 0.2), for a greater prolongation of IRP (16 +/- 0.6% of diastole), with increased diameter changes in this phase (displacement ratio = 3.3 +/- 2.3%, in Group B; 4.7 +/- 3.8%, in renovascular hypertension), for a normal displacement and velocity of slow and atrial filling, despite the impairment of rapid filling found in this group, too (% displacement and velocity, respectively: 19 +/- 5% and 1.8 +/- 0.6 cm/cm X sec).