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Biomedical subjects

B Morland

Publications and source records attributed to B Morland.

7 recordsLinked to original sources

Granulocyte colony-stimulating factor in established febrile neutropenia: a randomized study of pediatric patients.

PURPOSE: Infection in neutropenic patients is potentially life-threatening and carries important implications for hospital resource use. Prophylactic administration of cytokines may reduce the severity of neutropenia, but involves the treatment of all patients for the possible benefit of a minority. This study evaluates whether treatment with cytokines in the setting of established febrile neutropenia will influence outcome and be potentially more cost-effective. PATIENTS AND METHODS: In a double-blind study, pediatric patients with fever and severe neutropenia were randomized to receive granulocyte colony-stimulating factor ([G-CSF] filgrastim; 5 microg/kg/d) or placebo, in addition to antibiotics. The study protocol required a resolution of fever and a neutrophil count > or = 0.2 x 10(9)/L for hospital discharge. Patients could be randomized for up to four independent febrile episodes. A total of 186 episodes of febrile neutropenia were investigated. RESULTS: Patients randomized to G-CSF had a shorter hospital stay (median, 5 v 7 days; P = .04) and fewer days of antibiotic use (median, 5 v 6 days; P = .02). G-CSF-treated patients also had more rapid neutrophil recovery and higher neutrophil levels at discharge. The 2-day reduction in hospital stay reduced the median bed cost by 29% per patient admission (P = .04). CONCLUSION: Under the clinical guidelines of our institution, the use of G-CSF in the treatment of established febrile neutropenia produced a small but significant reduction in the time that children required antibiotics and hospital admission, with possible cost savings.

Anti-Bacterial Agents

Lymphadenopathy.

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Bacterial Infections

Synovial sarcoma of the larynx in a child: case report and histological appearances.

Synovial sarcoma of the larynx is extremely rare having been reported only six times previously in the literature. We add another case report, which to our knowledge is the first recorded case in a child. We discuss the alternative approach of combination chemotherapy and radiotherapy which in this case led to a remission lasting about 3 years. The immunohistological and ultrastructural characteristics of the tumour are also presented.

Adolescent

Effectiveness of combinations of bispecific antibodies for delivering saporin to human acute T-cell lymphoblastic leukaemia cell lines via CD7 and CD38 as cellular target molecules.

We have investigated the effectiveness of three different F(ab' gamma)2 bispecific antibodies (BsAb) for delivering the ribosome inactivating protein (RIP) saporin via the CD7 or CD38 cell surface molecules to the human T-ALL cell lines HSB-2 and HPB-ALL. Inhibition of 3H-leucine uptake by target cells was used as the parameter of cellular cytotoxicity. Used singly against HSB-2 cells in the presence of varied concentrations of saporin, an anti-CD7 BsAb, (HB2 x DB7-18) and an anti-CD38 BsAb (OKT10 x RabSap), gave 435- and 286-fold increases in saporin toxicity, respectively. For HPB-ALL cells the anti-CD7 BsAb performed poorly giving only an eight-fold increase in toxicity whilst on the same cell line the anti-CD38 BsAb was highly potent giving an 80,000-fold increase in saporin toxicity. A combination of both BsAb used together against HSB-2 cells was ten times more effective, than the best single BsAb HB2 x DB7-18 used alone. Kinetic studies conducted with HSB-2 cells revealed that the BsAb combination also gave an increased rate of protein synthesis inactivation in comparison to either BsAb used alone. These investigations clearly demonstrate a synergistic action when both BsAb are used in combination to target saporin against CD7 and CD38 expressed on the surface of the HSB-2 cell line.

ADP-ribosyl Cyclase

Characteristics and performance of a bispecific F (ab'gamma)2 antibody for delivering saporin to a CD7+ human acute T-cell leukaemia cell line.

We have investigated the efficacy of a F(ab'gamma)2 bispecific antibody (BsAb) with dual specificity for the CD7 molecule in one Fab arm and for the ribosome inactivating protein (rip) saporin in the other arm, for delivering saporin to the acute T-cell leukaemia cell line HSB-2. Saporin titration experiments revealed that BsAb increased the toxicity of saporin 435-fold for HSB-2 cells, reducing the IC50 for saporin alone from 0.1 mumol to 0.23 nmol when BsAb was included. The rate of protein synthesis inactivation brought about by BsAb-mediated toxin delivery to HSB-2 cells was very similar to that described for conventional immunotoxins (IT's) with a t10 (time taken for a one log inhibition of protein synthesis compared with controls) of 46 h obtained at a saporin concentration of 1 nmol and 226 h at 0.1 nmol. BsAb titration studies demonstrated a clear dose response effect of BsAb concentration on target cell protein synthesis inhibition and cell proliferation. The absolute specificity of toxin delivery was unequivocally demonstrated by a failure of BsAb to deliver an effective dose of saporin to the CD7- cell line HL60 and by the blocking of BsAb-mediated delivery of saporin to HSB-2 cells with an excess of F(ab)2 fragments of the anti-CD7 antibody, HB2. These studies have clearly demonstrated the effectiveness of this BsAb for delivering saporin to a T-ALL cell line utilising CD7 as the target molecule on the cell surface. BsAb's would therefore appear to offer a realistic alternative to IT's for toxin delivery to tumour cells and may even offer certain advantages over conventional IT's for clinical use.

Antibodies, Monoclonal