Granisetron, tropisetron, and ondansetron in the prevention of acute emesis induced by a combination of cisplatin-Adriamycin and by high-dose ifosfamide delivered in multiple-day continuous infusions.

The antiemetic efficacy of granisetron, ondansetron and tropisetron was evaluated in patients treated with cisplatin-Adriamycin (CDP/ADM) and ifosfamide (IFO) by continuous infusion (CI). In all, 90 patients with osteosarcoma were randomly assigned to receive granisetron (2 mg/m2), or ondansetron (5.3 mg/m2), or tropisetron (3.3 mg/m2) plus dexamethasone 8 mg/m2. Chemotherapy consisted of CDP (120 mg/m2, 48-h CI) followed by ADM (75 mg/m2, 24-h CI) and then, in the second cycle, delivered 3 weeks later, IFO 15 g/m2 (120-h CI). Complete protection (CP) from emesis was obtained on 59% of the 717 days of treatment, without significant differences among the three study drugs. A significantly higher rate of CP was obtained during chemotherapy with IFO than with CDP/ ADM (69% vs 44%; P<0.0001). The rate of CP declined from the first to the last day of treatment for both CDP/ADM (61% to 27%, P<0.0001) and IFO (95% to 43%) cycles (P<0.0001). When CDP/ ADM and IFO are delivered on multiple days by CI, granisetron, ondansetron and tropisetron have the same antiemetic efficacy, which declines from the first day onward through successive days.

Increased replication of T-cell-tropic HIV strains and CXC-chemokine receptor-4 induction in T cells treated with macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES beta-chemokines.

OBJECTIVE AND DESIGN: To study, in T-lymphoid cells, the effects of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES beta-chemokines on the replication of T-cell-tropic HIV-1 strains, since it has been reported that beta-chemokines interfere with the replication of macrophage-tropic HIV-1 strains, but not T-cell-tropic strains. METHODS: Freshly phytohaemagglutinin (PHA)-activated peripheral blood lymphocytes (PBL) and cultured PHA-activated T cells from healthy volunteers, as well as the C8166 T-cell line, were treated overnight with beta-chemokines before infection with T-cell-tropic HIV-1 isolates, or human T-lymphotropic virus type IIIB. HIV replication was followed by detecting the production of infectious particles, p24 antigen, and viral sequences. CXC-chemokine receptor (CXCR)-4 expression was followed by detection and quantification of specific transcripts. RESULTS: Pretreatment of T cells with MIP-1alpha, MIP-1beta and RANTES affected T-cell-tropic strains, increased the replication of HIV-1beta and HIV-1RPdT strains dose-dependently, as well as virus absorption and provirus DNA accumulation. These findings were associated with increased accumulation of CXCR-4 transcripts, and mediated by the protein tyrosine kinase signalling. Moreover, beta-chemokines stimulated PBL proliferation. CONCLUSIONS: Beta-chemokines increase the adsorption and replication of at least some T-cell-tropic HIV-1 strains, and this is related to stimulated expression of the CXCR-4 coreceptor.

[Local immunotherapy prevention of recurrent respiratory infections in children]. / Prevenzione con immunoterapia locale delle infezioni respiratorie ricorrenti nel bambino.

A group of 20 children aged between 2.5 and 10 years with recurrent respiratory infections (greater than 6/year) was treated with local immunotherapy (Biomunil spray) for a six-month period (October-March 1988/89). Referring to the same period on last year, a statistically significant decrease of upper respiratory infections was observed (p less than 0.001) as well as an increase of S-IgA rate (p less than 0.001) and less of serum IgA and IgG. The compliance and the tolerance of the drug was good.

Immunologic investigations in eight patients with incontinentia pigmenti.

We studied eight patients with incontinentia pigmenti to investigate the possibility of immunologic abnormalities. In six patients a defect of polymorphonuclear chemotaxis was revealed; lymphocyte subpopulations, serum immunoglobulin levels, and peripheral eosinophils were within normal limits. We hope these findings will stimulate further investigations into the mechanisms involved.

Clinical and laboratory findings in a new case of leukocyte adhesion deficiency.

We describe a child suffering from recurrent bacterial infections whose cells exhibited laboratory findings compatible with the leukocyte adhesion deficiency (LAD) syndrome. Surface marker analysis with monoclonal antibodies (MAbs) to the individual alpha and beta chains of LFA-1/Mac-1/p150,95 antigens revealed that the patient's neutrophils did not express the common beta chain and LFA-1/p150,95 alpha subunits, but reacted weakly with four different MAbs specific for the Mac-1 alpha chain; however, no glycoprotein was immunoprecipitated from the patient's cells using the same anti-Mac-1 alpha MAbs. Functional analysis of the patient's phagocytes revealed many of the defects in adherence-dependent functions (adherence, chemotaxis and phagocytosis) described in patients with LAD. The studies performed on the phagocytes of the patient's relatives showed normal phenotypes and function, suggesting the possibility of a non heritable form of disease in this family.

Prenatal immune status of fetuses of HIV-seropositive mothers.

Human immunodeficiency virus (HIV) has been isolated from fetal tissues as early as 13 weeks and later from fetal blood. These findings have raised the possibility of prenatal diagnosis of infected fetuses by identification of the virus in the fetal compartment. Study of the fetal immune status has proved reliable in prenatal diagnosis of congenital immunodeficiency, and we have tested the possibility to diagnose acquired immunodeficiency in utero by this approach. We studied T lymphocyte subsets and their mitogenic response in fetal blood obtained after elective termination at midgestation in 8 cases and at delivery in 26 cases of maternal HIV infection. Results have been compared to appropriate normal controls. No significant difference was found in terms of total lymphocytes, CD4 and CD8 populations and phytohemagglutinin responses. This indicates either that immunological parameters currently used to assess postnatal immunodeficiency are not reliable during intrauterine life or that the intrauterine environment and the transplacental passage of maternal antibodies interfere with development of prenatal immunodeficiency.

Myelokathexis associated with multiple congenital malformations: immunological study on phagocytic cells and lymphocytes.

A 5-year-old boy was first seen at the age of 11 months when he presented with growth retardation, skeletal dysmorphisms and neutropenia. Since then he has remained leukopenic except when he has pulmonary infections with a marked leukocytosis. Despite his neutropenia, marked myeloid hyperplasia was evident on marrow smear examination; many cells showed abnormally hypersegmented nuclei, with unusual shape or pyknotic nuclei. Phagocytic cells showed impaired phagocytosis, candidacidal activity, metabolic burst and chemotaxis. Moreover, the patient's serum generated less chemotactic activity than normal serum. These data indicate a selectively complex defect of the neutrophil during differentiation associated with the presence of an inhibitor of chemotactic factors in the patient's serum.

Incontinentia pigmenti and Behçet's syndrome: an unusual combination.

We describe an unusual case of a child who had had incontinentia pigmenti from birth and developed the clinical picture of Behçet's syndrome at five years of age. Among the various investigations performed, chemotactic activity of the polymorphonuclear leukocyte was found to be low. We discuss the possibility that there are common immunological abnormalities in the two syndromes.