Disseminated Mycobacterium terrae infection in a patient with advanced human immunodeficiency virus disease.

Mycobacterium terrae has been rarely implicated in human disease and never in patients infected with human immunodeficiency virus (HIV). We describe an HIV-infected patient with disseminated infection by M. terrae with pulmonary and cutaneous clinical manifestations. M. terrae was isolated from both sputum and urine, and identified by both conventional tests and high-performance liquid chromatography. Clinical and microbiological characteristics of this case are compared with those reported in the literature.     

Leukemic cell growth in SCID mice as a predictor of relapse in high- risk B-lineage acute lymphoblastic leukemia

Mice with severe combined immunodeficiency (SCID) provide a model system to examine the in vivo homing, engraftment, and growth patterns of normal and malignant human hematopoietic cells. The relation between leukemic cell growth in this model and the treatment outcome in patients from whom cells were derived has not been established. Leukemic cells from 42 children with newly diagnosed high-risk B- lineage acute lymphoblastic leukemia were inoculated intravenously into CB.17 SCID mice. Mice were killed at 12 weeks or when they became moribund as a result of disseminated leukemia. All mice were necropsied and subjected to a series of laboratory studies to assess their burden of human leukemic cells. Twenty-three patients whose leukemic cells caused histopathologically detectable leukemia in SCID mice had a significantly higher relapse rate than the 19 patients whose leukemic cells did not (estimated 5-year event-free survival: 29.5% v 94.7%; 95% confidence intervals, 11.2% to 50.7% v 68.1% to 99.2%; P < .0001 by log- rank test). The occurrence of overt leukemia in SCID mice was was a highly significant predictor of patient relapse. The estimated instantaneous risk of relapse for patients whose leukemic cells caused overt leukemia in SCID mice was 21.5-fold greater than that for the remaining patients. Thus, growth of human leukemic cells in SCID mice is a strong and independent predictor of relapse in patients with newly diagnosed high-risk B-lineage acute lymphoblastic leukemia.     

Monoclonal antibody T101 in T cell malignancies: a clinical, pharmacokinetic, and immunologic correlation

Eight patients with cutaneous T cell lymphomas (CTCL) and five with various other T cell malignancies were treated with mouse monoclonal antibody (MoAb) T101. Doses of 1 to 500 mg were administered weekly over a two-hour period and resulted in one complete remission (convoluted T cell lymphoma) and one partial remission (CTCL). Remission duration was 6 weeks and 3 months, respectively. Frequent toxicities were pruritus, hives, flushing, and shortness of breath. Supraventricular arrhythmias and blood pressure instability were also observed. Complete targeting of peripheral blood T cells was achieved with 1 mg of MoAb in the nonleukemic patients (WBC less than 10,000/microL), and free, bioavailable antibody was present at the next (10-mg) dose level. Even higher doses resulted in substantial antibody excess that persisted for as long as 6 weeks. Serum concentrations of MoAb decreased with increasing number of peripheral blood T cells, and 25 to 35 mg of T101 were required for induction of antibody excess in leukemic patients. Excess antibody induced antigenic modulation, which was of consequence only if MoAb excess persisted to the next treatment. In the original treatment, the rapidly administered MoAb was able to target and remove peripheral blood T cells before the development of antigenic modulation. Antimouse antibodies developed in three patients. Their presence rendered further therapy ineffective and was associated with an anaphylactic reaction in one patient. Development of these antibodies could not be predicted by lymphoproliferative assays. In these assays, however, the T101 protein strongly stimulated the mononuclear cells of the patient who reached the only complete remission of this trial. Immunologic stimulation by the MoAb thus might have played a role in this patient's antitumor response. In summary, therapy with MoAb T101 was specific but only modestly efficacious. Rapid infusion of nonmodulating doses of antibody provided excellent targeting and removal of peripheral blood T cells and might be a valid approach in future trials with immunoconjugated T101.     

Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in rheumatoid arthritis patients following anti- tumour necrosis factor-alpha (cA2) therapy

Matrix metalloproteinase (MMP)-1 and MMP-3 levels were measured in serum samples from rheumatoid arthritis (RA) patients undergoing a double-blinded placebo-controlled trial with the chimaeric anti-tumour necrosis factor (TNF)-alpha antibody cA2. Both MMP-1 (P < 0.015), but to a larger extent MMP-3 (P < 0.001) levels were elevated in all RA patients prior to the commencement of the trial compared with normal control sera. Following cA2 therapy, MMP-1 and MMP-3 levels were assessed in the placebo, and 1 and 10 mg/kg cA2-treated groups at 7, 14, 21 and 28 days. In both the 1 and the 10 mg/kg cA2-treated groups, a significant decrease in serum MMP-3 levels at all time points was observed, reducing maximally to 41% of pre-infusion values at day 7. MMP-1 levels were also reduced, but less dramatically than MMP-3, to 85% of pre-infusion values after 14 days in the 10 mg/kg cA2 treated group. In a separate non-placebo-controlled study, we also evaluated the tissue inhibitor of metalloproteinase (TIMP)-1 levels in plasma following cA2 infusion. Pre-infusion TIMP-1 levels were above the normal control range, but were significantly reduced (P < 0.035) 14 days after infusion to 72% of pre-infusion values. This study confirms previous reports that MMP-3 levels are elevated and correlate with measures of inflammation in RA, and furthermore demonstrate that serum MMP-3 and MMP-1 levels are downmodulated following anti-TNF-alpha antibody therapy. Whilst serum MMP-3 levels correlated with C-reactive protein (CRP) both prior to and following anti-TNF-alpha antibody therapy, it remains to be demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and bone resorptive processes which are evident in this disease.      

Production of antibodies to Little cherry virus 1 coat protein by DNA prime and protein boost immunization

Little cherry, an economically important disease of cherry is caused by at least two different viruses. One of these is Little cherry virus 1 (LChV-1) for the detection of which no efficient serological tools are available, so that diagnosis is based on molecular methods. In this study, different immunization strategies for producing antibodies against the viral coat protein of LChV-1 were tried, using either purified virus preparations, or bacterially expressed protein, or a DNA vector that expressed the cloned coat protein (CP) gene in vivo. Effective induction of specific antibodies to LChV-1 CP was obtained using DNA intramuscular immunization followed by a single boost with the recombinant protein. The entire coat protein sequence was cloned in a mammalian expression vector and, after being coated by an amphiphilic non-toxic reagent was delivered into rabbit. A protein boost increased the specific immune response against the virus protein. The sensitivity of this antiserum is lower if compared with that of antisera raised conventionally against other viruses, thus it requires improvements for use for diagnostic purposes.     

Therapy vs no therapy for bacteriuria in elderly ambulatory nonhospitalized women

This prospective randomized study was undertaken to determine the efficacy of antimicrobial therapy compared with no therapy for bacteriuria in elderly ambulatory nonhospitalized women. Sixty-one women (mean age, 85.8 years) with bacteriuria were in the no therapy control group and 63 women (mean age, 85.8 years) with bacteriuria were in the therapy group; none had symptoms of urinary tract infection. One short course of antimicrobial therapy achieved a cure rate of 68.3% (43 of 63 women cured) two weeks after treatment. During the six-month follow-up period, ten (16.4%) of 61 women in the no therapy group and five (7.9%) of 63 women in the therapy group developed symptomatic urinary tract infection. At the time of six-month follow-up, 19 (34.5%) of 55 women in the no therapy group and 35 (63.6%) of 55 women in the therapy group did not have bacteriuria. We conclude that for asymptomatic bacteriuria in elderly ambulatory nonhospitalized women, short-course antimicrobial therapy is effective at two-week follow-up and that antimicrobial therapy can eliminate bacteriuria in most of these women for at least a six-month period.