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Biomedical subjects

L Sviland

Publications and source records attributed to L Sviland.

66 records · Page 4Linked to original sources
PubMed1990

An in vitro predictive test for clinical graft-versus-host disease in allogeneic bone marrow transplant recipients.

An in vitro skin explant model has been used in an attempt to predict the severity of graft-versus-host disease (GVHD) in HLA-identical donor-recipient pairs. The skin explant model involves the use of donor lymphocytes which have been sensitized against recipient lymphocytes in vitro and then co-cultured with the recipient's skin. Thirteen patients were studied in a prospective manner and results from the skin explant model compared with the clinical status of the patient post-transplant showed good correlation (p less than 0.001). Results from T cell-depletion studies indicated a role for both CD4 and CD8 positive cells in GVHD. In conclusion the results confirmed that the skin explant assay is a useful and predictive test of GVHD in humans.

Adult↗
PubMed1989

A preliminary study of serum class II levels in healthy individuals and bone-marrow transplant patients.

A double-determinant ELISA has been developed to measure class II major histocompatibility complex molecules in blood from healthy individuals and patients who received either an allogeneic or an autologous bone-marrow transplant. Levels were higher in pre-transplant patients than in healthy individuals, and in the majority of patients, these levels rose even higher at 4 weeks post-transplantation. At later times after transplantation, it was difficult to draw firm conclusions, because the number of values available were too limited. Nevertheless, in the autologous group with no graft-versus-host disease (GVHD), levels were consistently lower at 6 months and one year; in the allogeneic group these long-term levels varied. As class II antigens are expressed on skin and rectal epithelia in GVHD, this study suggests that serial measurement of serum class II levels may be useful for monitoring GVHD in bone-marrow transplantation.

Adult↗
PubMed1989

Improved method for immunoperoxidase detection of membrane antigens in frozen sections.

The visualisation of membrane antigens in frozen sections using metal-enhanced 3,3'diaminobenzidine (DAB) was investigated. Particular attention was paid to the degree of reaction enhancement, the disruptive effect on morphological detail, and the ease of the techniques. The best result was obtained using nickel-modified DAB at pH 6.0 to develop the peroxidase enzyme, with further enhancement in cobalt chloride at neutral pH. Silver methenamine enhancement is also possible but can give rise to non-specific or background staining.

3,3'-Diaminobenzidine↗
PubMed1989

Expression of MHC class I and II antigens by keratinocytes and enterocytes in acute graft-versus-host disease. Newcastle Bone Marrow Transplant Group.

The expression of MHC class I and subgroups of class II antigens by keratinocytes and enterocytes has been investigated in patients receiving autologous and allogeneic bone marrow transplants. Allogeneic recipients with graft-versus-host disease (GVHD) expressed all the class II antigens HLA DR, DP and DQ more frequently than pretransplant patients, autologous or allogeneic recipients without GVHD post-BMT (p less than 0.01). Staining for DP and DQ was never detected without DR being present. Whenever there was a lymphocytic infiltrate in the epidermis or single cell necrosis in the gut, DR was expressed on the epithelium. There was no difference in class I expression in GVHD. This study further increases the immunopathological characterization of acute GVHD which may improve the understanding of its pathogenesis.

Acute Disease↗
PubMed1988

Class II antigen expression by keratinocytes and enterocytes--an early feature of graft-versus-host-disease.

HLA-DR expression by keratinocytes and enterocytes was studied in 23 patients undergoing BMT (12 autologous; 11 allogeneic). Two monoclonal antibodies were used to detect the HLA-DR antigen. Only in two patients before transplant and in one following autologous BMT was HLA-DR expressed on keratinocytes. Of 11 allogeneic recipients, 7 developed clinical GVHD, and HLA-DR-positive keratinocytes were seen in 6 of these. HLA-DR was expressed by enterocytes in 5 patients with GVHD and 4 of these also showed HLA-DR expression by keratinocytes. HLA-DR expression by keratinocytes correlated well with clinical GVHD. Expression of this antigen by enterocytes was associated with characteristic histological appearances of GVHD, even in the absence of intestinal symptoms. A combination of traditional and immunocytochemical techniques offers a sensitive and accurate method of confirming GVHD before it becomes florid.

Epidermal Cells↗
PubMed1988

Histological features of skin and rectal biopsy specimens after autologous and allogeneic bone marrow transplantation.

The histological appearances of skin and rectal biopsy specimens were studied in 31 bone marrow transplant recipients (13 autologous, 18 allogeneic) before transplant, at 28 days, at six months, and as soon as graft versus host disease (GVHD) was clinically suspected. Grades I and II skin changes were commonly seen in patients before transplant and in the autologous group after transplant, as well as in most of the allogeneic recipients with suspected GVHD. Epidermal lymphocytic infiltration was seen only in allogeneic recipients, with clinical GVHD following transplant, but this was not a consistent finding and no other histological features were seen which would distinguish early GVHD from changes caused by cytotoxic agents. Rectal biopsy specimens, however, were normal in patients before transplant and in autologous recipients at 28 days; single cell necrosis of crypt cells was seen only in six of 13 allogeneic recipients studied after transplant with clinical skin GVHD but no gastrointestinal symptoms. Skin changes greater than I and II are required for the histological diagnosis of GVHD. Rectal changes are more specific and may be present despite a lack of intestinal symptoms.

Adolescent↗
PubMed1988

Skin explant culture as a model for cutaneous graft-versus-host disease in humans.

An in vitro skin explant model for graft-versus-host disease (GVHD) in humans has been used to study the role of effector T cells in the histological pathogenesis of GVHD. In 11 of 12 experiments clear GVHD changes of grades II-IV were induced in HLA-mismatched skin explants cultured with allogeneic T cells sensitized by in vitro mixed lymphocyte culture. The role of effector T cells was investigated by comparing results before and after removal of CD3 positive cells, and CD4 positive and CD8 positive T cell-subsets by antibody and complement cytolysis from responder populations. Only total removal of CD3 positive T cells prevented histopathological lesions of GVHD in the skin biopsy specimens. The results also demonstrated that the CD4 positive population caused the greatest degree of GVHD in vitro in skin biopsy specimens and direct infiltration into skin by cells is not required for changes to become evident. These results confirm the early results on animal models and demonstrate the use of the skin explant model as a tool for studying the biology of GVHD in humans.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Interaction of cimetidine with oral melphalan. A pharmacokinetic study.

The effects of pretreatment with cimetidine (200 mg three times daily, 400 mg at night) on the pharmacokinetics of oral melphalan (10 mg) have been investigated in patients with multiple myeloma. Cimetidine pretreatment reduced the bioavailability of oral melphalan by approximately 30% (P less than 0.05). The elimination rate of melphalan from plasma was significantly increased by cimetidine (P less than 0.05), the half-life being reduced from 1.94 +/- 0.55 h to 1.57 +/- 0.53 h. Cimetidine appeared to reduce the interindividual variability in melphalan absorption, but at the cost of reduced bioavailability.

Administration, Oral↗
PubMed1987

Factors influencing haematological measurements in healthy adults.

By studying 516 healthy adults normal reference intervals were established for the Coulter "S" haematological indices with the plasma ferritin, B12, folate and red cell folate in a subgroup of 306. Significant sex related differences were found for all measurements other than MCV, MCH and B12. After allowing for these sex related differences, the effects of age, body size, fasting, smoking, alcohol, exercise and contraceptive pill usage on the parameters studied was defined.

Adolescent↗
PubMed1987

Short course intermediate dose intravenous melphalan therapy in myeloma--relation to early emergence of drug resistance (phase II study).

Intermediate dose intravenous melphalan at a dose of 15 mg/m2 x 4 given at 21-day intervals has been evaluated in 20 consecutive patients. The aims were to assess the time to obtain maximal response, duration of response and response to reintroduction of intravenous melphalan on relapse. Median time to maximal response was 17 weeks. Four patients achieved a complete response with complete disappearance of paraprotein. On relapse, reintroduction of intravenous melphalan was unsuccessful in causing a reduction of paraprotein, suggesting that resistance to this dose of melphalan occurs early even in responding patients.

Drug Evaluation↗