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Biomedical subjects

J Biggs

Publications and source records attributed to J Biggs.

At least 73 records · Page 4Linked to original sources
PubMed1987

Avascular necrosis of the femoral head secondary to corticosteroid therapy for graft-versus-host disease after marrow transplantation: effective therapy with hip arthroplasty.

Of 50 patients surviving 2 years or longer after HLA-identical sibling bone marrow transplantation for haematological malignancy or severe aplastic anaemia, five developed avascular necrosis of the femoral head. All had previously received corticosteroid therapy post-transplant for graft-versus-host disease. Median day of onset of symptoms was 545 days post-transplant (range 249-731). Clinical, radiological and radionuclide findings were typical of osteonecrosis. One patient has had bilateral hemiarthroplasties and one total hip replacements performed, both with excellent results. Bilateral arthroplasties are planned for a third patient but, interestingly, the disease process in the other two patients has been relatively mild with no progression over a period of greater than 256 and greater than 825 days, respectively. Since one patient had as little as 14 days treatment with prednisone, this complication should be borne in mind when designing prophylactic regimens for minimisation of GVHD that include corticosteroids.

Adrenal Cortex Hormones↗
PubMed1987

Late onset transfusion-dependent anaemia with thrombocytopenia secondary to marrow fibrosis and hypoplasia associated with chronic graft-versus-host disease.

Late onset transfusion-dependent anaemia is very rare in the presence of sustained engraftment after HLA-identical sibling bone marrow transplantation. The only previously described consistent cause is pyridoxine-responsive sideroblastic anaemia. We describe here a second cause, marrow hypoplasia and fibrosis, occurring in association with extensive chronic graft-versus-host disease (GVHD). A 20-year-old Caucasian male who received cyclophosphamide and fractionated total body irradiation followed by an unmanipulated HLA-identical sibling marrow transplant from his sister for acute nonlymphoblastic leukaemia in first remission developed chronic GVHD of the skin and mouth at day 101 post-transplant. At day 689 post-transplant, he developed leuco-erythroblastic anaemia with thrombocytopenia, due to patchy marrow hypoplasia and fibrosis. Between days 689 and 1987 post-transplant he received 71 units of packed red cells, requiring transfusion approximately monthly. He remains well although still on prednisone for chronic GVHD of skin and is receiving desferrioxamine 4 g five nights/week i.v. as prophylaxis for iron overload.

Adult↗
PubMed1987

Comparison of alprazolam and imipramine for treatment of outpatient depression.

A 6-week double-blind comparison of the therapeutic efficacy of alprazolam and imipramine in 90 depressed psychiatric outpatients revealed a significantly superior response to alprazolam in the first 2 weeks of treatment as measured by total scores on the Hamilton Rating Scale for Depression and the Brief Psychiatric Rating Scale. Further analyses revealed that all significant differences could be accounted for by the superior effect of alprazolam on sleep disturbance. By the end of Weeks 4 and 6, no significant differences in therapeutic response between the two treatment groups were noted, with patients in both groups evidencing improvement on all measures. A differentially high dropout rate among patients in the imipramine treatment group posed a problem for interpretation of results in the latter weeks of treatment.

Adolescent↗
PubMed1986

Hemopoietic progenitor cell function after HLA-identical sibling bone marrow transplantation: influence of chronic graft-versus-host disease.

We examined hemopoietic reconstitution during the first 12 months post-transplant in 31 patients given high-dose cyclophosphamide, total body irradiation and an HLA-identical sibling marrow transplant for hematological malignancy. Unexpectedly, we found marrow CFU-gm and marrow CFU-e cells to be denser than normal throughout the first year post-transplant. While functionally adequate neutrophil and platelet counts were achieved in the first six weeks post-transplant, there were defects in hemopoietic progenitor cell function during the first year post-transplant. Although we could detect no influence from acute graft-versus-host disease (GVHD), chronic GVHD adversely affected the growth of both myeloid and erythroid blood progenitor cells.

Bone Marrow Cells↗
PubMed1986

Mononuclear cell subpopulations in the skin defined by monoclonal antibodies after HLA-identical sibling marrow transplantation.

Mononuclear cell subpopulations present in the skin of 36 recipients of HLA-identical sibling marrow transplants were defined by immunoperoxidase using a battery of monoclonal antibodies to cell surface differentiation antigens. The T4-positive (T4+) (helper-inducer T cells), T8+ (cytotoxic-suppressor T cells) and the T6+ (Langerhans cells) decreased in number early post transplant and returned towards normal numbers from day 42 onwards. There was no evidence that either the T4+ or the T8+ subset was involved in cell-to-cell contact damage in acute graft-versus-host disease (GVHD). The paucity of lymphoid cell infiltration of the epidermis in acute GVHD suggested the possibility of a soluble factor being responsible for basal layer damage. In patients with chronic GVHD there was no evidence of T4+ lymphocyte involvement, but T8+ lymphocytes were present in increased numbers, suggesting a role for the T8+ population in the skin lesions of chronic GVHD, or possibly a reflection of the pattern of T4+ and T8+ cell reconstitution in the blood post-transplant. Finally, our study provided no evidence that BI+ (B cells), Leu 7+ (natural killer cells), OKMI+ (histiocytes) or OKT1O+ cells were involved in cell-to-cell contact damage in either acute or chronic GVHD.

Bone Marrow Transplantation↗
PubMed1986

Female marrow donors increase the risk of acute graft-versus-host disease: effect of donor age and parity and analysis of cell subpopulations in the donor marrow inoculum.

We evaluated 27 factors for their influence on acute graft-versus-host disease (GVHD) in 40 recipients of HLA-identical sibling marrow transplants. These factors included the doses of mononuclear cell subpopulations present in the donor marrow inoculum quantitated using a panel of monoclonal antibodies. Female donors were associated with increased severity of acute GVHD, and the older the female donor the greater this effect. Increasing donor parity was also associated with an increased risk of acute GVHD. The number of T cells, T cells subsets, natural killer cells and monocytes infused did not influence the incidence or severity of acute GVHD in this study, and we could not explain the influence of female donors and of female donor age on acute GVHD by the cellular content of their marrow inocula. We postulate that non-HLA histocompatibility antigen disparity is a more important determinant for acute GVHD than the number of infused donor T cells, especially when female donors are used. The association between acute GVHD and increasing parity suggests that some female marrow donors have been pre-sensitized to their respective recipients by preceding pregnancies.

Acute Disease↗
PubMed1986

Second marrow transplants for recurrence of haematological malignancy.

Nine patients with haematological malignancy relapsed 3-32 months after receiving cyclophosphamide 120 mg/kg, 12-14 Gy fractionated total body irradiation and an HLA-identical sibling bone marrow transplant. They were reconditioned with melphalan 180-220 mg/m2 and retransplanted using the same donor and the same cyclosporin regimen as prophylaxis for graft-versus-host disease (GVHD). Three of the nine remain alive greater than 81, greater than 33, and greater than 36 months after second transplant. While the rate of marrow engraftment, the incidence of acute GVHD and the incidence of interstitial pneumonitis were similar after first and second transplants, the use of melphalan before second transplant was associated with increased nephrotoxicity and oropharyngeal mucositis. The present study shows that second narrow transplants are feasible, can produce prolonged remission of haematological malignancies and should be considered in appropriate patients who relapse after first marrow transplant.

Actuarial Analysis↗
PubMed1986

PUVA therapy for drug-resistant graft-versus-host disease.

Ultraviolet irradiation is known to diminish the functional capacity of cells of the immune system. We have used ultraviolet A irradiation in combination with psoralen (PUVA) to treat three patients with drug-resistant graft-versus-host disease (GVHD) of the skin or mouth. Each of the three patients had received an HLA-identical sibling bone marrow transplant for haematological malignancy or severe aplastic anaemia. One patient developed acute GVHD of skin and mouth and two patients developed chronic GVHD of the mouth, which did not respond to conventional immunosuppressive drugs including cyclosporin and methyl prednisolone (all three patients) and anti-thymocyte globulin (two patients). PUVA irradiation to the skin was given at a dose of 0.75-1.25 J (joules) daily for four days per week and that to the mouth at 0.75 J daily four days per week. Before each treatment, 8-methoxypsoralen (0.6 mg/kg) was given orally as a photosensitizer. Each patient improved considerably and in each case the dosage of conventional immunosuppression was reduced. No flare was noted in the two patients with chronic GVHD of the mouth at 1 month after the end of treatment. PUVA irradiation is a useful therapeutic adjunct in GVHD affecting skin and mouth and appears to confer a steroid or cyclosporin sparing effect.

Acute Disease↗
PubMed1985

Structure of the eukaryotic transcription apparatus: features of the gene for the largest subunit of Drosophila RNA polymerase II.

The Drosophila melanogaster RpII215 locus encodes the largest subunit of RNA polymerase II. We have now mapped the 7 kb transcript of the locus and have determined that it contains four exons and three introns. By sequencing 2582 nucleotides from the promoter-proximal end of the RpII215 locus, we have precisely mapped the start site of transcription and the splice sites of the first intron. Segments of the amino acid sequence predicted by the only long open reading frame of the RpII215 gene transcript display striking homology with corresponding segments of the beta subunit of E. coli RNA polymerase.

Amino Acid Sequence↗
PubMed1985

Lack of correlation between nucleated bone marrow cell dose, marrow CFU-GM dose or marrow CFU-E dose and the rate of HLA-identical sibling marrow engraftment.

There was no correlation between the rate of marrow engraftment and the number of nucleated bone marrow cells infused into 50 HLA-identical sibling marrow graft recipients with haematological malignancy conditioned with cyclophosphamide and fractionated total body irradiation, and immunosuppressed with either cyclosporin (42 patients) or methotrexate (eight patients). Similarly, there was no correlation between the number of marrow CFU-GM or CFU-e infused into recipients immunosuppressed with cyclosporin. The data show that recipients of HLA-identical sibling marrow allografts conditioned with cyclophosphamide and total body irradiation require less than 3 X 10(8) nucleated bone marrow cells/kg recipient weight to ensure engraftment, and throw doubt on the relevance of measuring committed progenitor cells in the donor marrow to assess the likelihood of subsequent haemopoietic reconstitution after matched sibling transplantation.

Body Weight↗