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Biomedical subjects

K Brigham

Publications and source records attributed to K Brigham.

8 recordsLinked to original sources
PubMed2001

CAMPATH-1M T-cell depleted BMT for SCID: long-term follow-up of 19 children treated 1987-98 in a single center.

BACKGROUND: SCID can be cured by BMT. Depletion of mature T cells from BM has enabled HLA non-identical stem-cell transplantation. We report the outcome of 30 patients treated with 37 T-cell depleted BMT procedures using CAMPATH-1M in vitro between 1987-98 in a single center. METHODS: Immune reconstitution and quality-of-life were assessed in 19 longterm survivors. All but two received pre-transplant conditioning. T- and B-cell chimerism, numbers and function were analyzed during a median follow-up of 5.3 years (range 1.33-12). RESULTS: The overall engraftment rate was 59%, six children required repeated BMT and the survival rate was 63%. All have donor T cells, 58% normal T-cell numbers and 74% normal T-cell function. Of 17 evaluated, 16 patients (94%) have normal IgM and IgG levels, and production of specific Abs to protein Ags, but only 5/16 (31%) have a good response to pneumococcal polysaccharide. Early and late post-BMT complications were rare and there were no delayed deaths. Only one child continues on long-term i.v. Ig 4-years post-BMT. Eleven children died (37%). DISCUSSION: CAMPATH-1M T-cell depleted BMT for SCID resulted in 63% survival. Deaths of 11 children were mainly due to pre-existing infections. Seventeen of 19 long-term survivors have normal immune function and good quality-of-life.

Alemtuzumab↗
PubMed1997

In vitro T cell depletion using Campath 1M for mismatched BMT for severe combined immunodeficiency (SCID).

Bone marrow transplantation is the only curative treatment for children with severe combined immunodeficiency (SCID). In the absence of an HLA-identical sibling, haploidentical parental donor marrow can be used provided it is depleted of T cells to prevent otherwise inevitable GVHD. Campath 1M has been successfully used for this procedure in several centres. In our centre 17 SCID patients plus one with combined immunodeficiency (CID) were transplanted with Campath 1M T cell-depleted bone marrow. Progenitor cell recovery, before and after T cell depletion, was monitored using granulocyte-macrophage colony-forming cell assays (GMCFU) and CD34 analysis. The numbers of GMCFU/kg transplanted correlated with engraftment and survival post-transplant and monitoring CD34+ cell numbers in the T cell-depleted marrow pretransplant may be an additional indicator of successful engraftment. Use of a buffy coat marrow preparation with restriction of the number of T cells to < 5 x 10(5)/kg was associated with graft failure in four and death in five of eight children, probably because too few stem cells were infused. T cell depletion of a mononuclear cell preparation of donor marrow with no arbitrary ceiling of infused T cells is highly effective at preventing clinically important GVHD and cured nine out of 10 children transplanted with such material.

Antibodies, Monoclonal↗
PubMed1987

Factor II, VII, IX and X concentrations in patients receiving long term warfarin.

Using standard one stage clotting assays the concentrations of factors II, VII, IX and X were determined in 37 patients stabilised on warfarin for between three months and 17 years. Contrary to popular belief, the concentrations were not equally depressed, with factor X the lowest, factor II at intermediate value, factors VII and IX the highest. Some 71% of the variance of the British corrected ratio (BCR) could be accounted for by measurement of the factors assayed. Analysis of this variance showed 91% of the explained variance attributable to factor II, 7% to factor VII, 1.6% to factor IX and 0.4% to factor X. With the sudden and recent withdrawal of human thromboplastin, investigation of the sensitivities of the animal thromboplastins to changes in vitamin K dependent factors in orally anticoagulated patients is needed to ensure that the potentially alarming falls in factors II and X in these patients are being adequately detected.

Adult↗
PubMed1977

Serum ferritin in juvenile chronic polyarthritis.

Six children with juvenile chronic polyarthritis were studied and their disease activity correlated with haematological values including serum ferritin. The latter is often raised above reference values, but even when within them appears to fluctuate significantly and correlates more closely with disease activity than any of the other parameters measured. We conclude that the serial measurement of serum ferritin may be a useful guide to the management of such children.

Adolescent↗
PubMedDate not supplied

Enhancement of liposome-mediated gene transfer to human airway epithelial cells by replication-deficient adenovirus.

We hypothesized that replication-deficient adenovirus (Ad), when complexed with plasmid DNA (pl) and cationic liposomes (L), would enhance liposome-mediated gene transfer in cultured human airway epithelial cells. Pl/L/Ad complexes were formed using charge-charge interactions. A gel electrophoresis retardation assay showed plasmid DNA to be associated with the virus in a high-molecular-weight, low-mobility complex, the diameter of which was 300 to 350 nm. Compared to pl/L alone, pl/L/Ad enhanced luciferase expression on average by 1 log-fold in human airway epithelial cells which express either mutant or wild-type cystic fibrosis transmembrane conductance regulator (CFTR). Transgene expression was sustained at high levels for up to 7 days following transfection with pl/L/Ad. Using a heat-stable alkaline phosphatase reporter gene, we showed that a larger fraction of cells was transfected by pl/L/Ad compared to pl/L. Finally, cells were exposed to Ad for 0 to 24 hours prior to pl/L or exposed to pl/L prior to Ad. We found that enhancement was significantly greater using pl/L/Ad compared to the simultaneous addition of Ad with the pl/L complexes. In addition, when pl/L was added 4 to 24 hours prior to Ad, some enhancement was found, suggesting that plasmid DNA remained in a compartment in the cell for several hours and became available for transcription with the addition of Ad. When Ad was added prior to pl/L, enhancement was found suggesting that the effect of the virus on cell membranes may persist for up to 24 hours. We conclude that the tripartite pl/L/Ad complex significantly enhances liposome-mediated transgene expression for a prolonged period of time in human bronchial epithelial cells.

Adenoviridae↗