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P J Hamilton

Publications and source records attributed to P J Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed1994

Transfusion-associated graft-versus-host disease in fludarabine-treated B-chronic lymphocytic leukaemia.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but serious complication of blood component therapy in patients with haematological malignancies. B-chronic lymphocytic leukaemia (B-CLL), however, has rarely been associated with TA-GVHD. We report three patients with advanced B-CLL who developed TA-GVHD. All these had been treated with fludarabine. Suppression of T cells by fludarabine may have contributed to an increased susceptibility to TA-GVHD. The use of irradiated blood products to prevent this complication should be considered for patients with advanced B-CLL treated with fludarabine or other purine analogues.

Antineoplastic Agents↗
PubMed1994

Cytokine involvement in predicting clinical graft-versus-host disease in allogeneic bone marrow transplant recipients.

An in vitro skin explant model has been used to predict the severity of acute graft-versus-host disease (GVHD) in 34 HLA-identical bone marrow transplant recipients (correlation coefficient 0.6 p < 0.001). Supernatants from HLA-matched patient/donor mixed lymphocyte cultures (MLCs) were analysed for levels of tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma). High levels of both cytokines correlated with the development of GVHD grades II or above (p < 0.05). The supernatants were also tested for induction of class II MHC antigen expression on third party skin and results correlated with clinical outcome in 17 of 22 cases (77%) (correlation coefficient 0.65, p < 0.001). The results suggest that measurement of both TNF alpha and IFN gamma in HLA-matched MLC supernatants is of predictive value and that the skin explant model is a useful model for studying the aetiology of GVHD in humans.

Adolescent↗
PubMed1994

Raised intracellular glutathione levels correlate with in vitro resistance to cytotoxic drugs in leukaemic cells from patients with acute lymphoblastic leukemia.

Lymphoblasts were separated from the peripheral blood or bone marrow of 19 children (age 1-15, median 4 years) and 13 adults (age 18-59, median 47 years) with acute lymphoblastic leukaemia (ALL). Twenty-one samples were examined at presentation (16 from children and five from adults) and 13 at relapse (three children and ten adults). Glutathione (GSH) levels in leukaemic blasts were compared with in vitro sensitivity to a variety of cytotoxic drugs assessed using 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as an indicator of cell viability. There was a statistically significant positive correlation between GSH levels and in vitro sensitivity to daunorubicin (Spearman's rank correlation coefficient rs = 0.38, p < 0.04), melphalan (rs = 0.39, p < 0.04) and prednisolone (rs = 0.48, p < 0.01), but not mitozantrone, etoposide or 6-thioguanine. There was no statistically significant difference in median GSH levels between blasts from children and adults or between samples taken at presentation or relapse. The sample median GSH levels in blasts from patients who responded to therapy (n = 21) and those who did not (n = 7) were 1.05 fmol/cell (97.3% confidence interval (CI) 0.78-1.52) and 2.66 fmol/cell (98.4% CI 0.53-5) respectively, and this difference was statistically significant (p < 0.02, Mann-Whitney U test). In two patients for whom paired samples were available, GSH levels in blasts on relapse were greater than 2-fold higher than on presentation. These results provide evidence that elevation of GSH in leukaemic blasts may be associated with resistance to drugs used in the treatment of children and adults with ALL.

Adolescent↗
PubMed1993

Collagenase digestion of bone marrow trephine biopsy specimens: an important adjunct to haematological diagnosis when marrow aspiration fails.

Failure to obtain sufficient material from marrow aspiration (dry tap) posed a diagnostic problem in two patients with pancytopenia. By using collagenase digestion of the trephine biopsy specimen, a precise diagnosis was reached. This technique is very useful because it permits flow cytometric and immunocytochemical analyses of cell suspensions obtained after collagenase digestion of the trephine biopsy specimen core. Acute leukaemia presenting with a dry tap can therefore be accurately immunophenotyped. The technique is easy to perform and merits wider use.

Adult↗
PubMed1993

Prognostic importance of histological and immunopathological assessment of skin and rectal biopsies in patients with GVHD.

Skin and rectal biopsies from patients with GVHD were examined histologically and immunopathologically before and after treatment for the disease. The patients were divided into two groups: those showing a good response to treatment and those showing a poor or no response. The aims of the study were to assess the possibility of predicting the response to treatment and to compare good and poor responders after treatment. The results show that there are no features on either skin or rectal biopsy that could identify those patients with early GVHD who would respond to treatment. Following treatment with steroids there was no change histologically in the grading of the skin biopsy whereas the rectal biopsy showed improvement in six of nine good responders and no improvement in the poor responders. There was an increase in infiltrating lymphocytes in both the skin and rectum of patients showing a poor response and this is most likely due to the ongoing immune reaction. The pre-treatment biopsy did not show any features that would predict this development and was therefore of no prognostic value. However, examination of skin and rectal biopsies may aid in determining whether patients are responding to the treatment given for GVHD.

Adolescent↗
PubMed1992

Acute lymphoblastic leukemia in patients aged 60 years and over: a population-based study of incidence and outcome.

Data on all patients aged 60 or older in whom a diagnosis of acute lymphoblastic leukemia (ALL) was made in the Northern Health Region of the United Kingdom, over a period of 8 1/2 years, were studied to determine the incidence and range of biological subtypes, and the outcome of a variety of therapeutic approaches. Forty-nine cases were diagnosed (31% of all adult ALL), giving an incidence of 0.9 per 100,000 age-specific population (ASP). Immunophenotyping was performed in 41 patients. Eighteen had common, two T-ALL, 10 null, and 7 B-ALL. Four were biphenotypic with both lymphoid and myeloid markers. One patient refused treatment and four were considered too frail for chemotherapy. Twenty-two were treated palliatively. Aggressive "curative" treatment was planned for 22, but three died before it started. The actuarial survival for the whole group was 4%. The median survival of the palliatively treated group was 1 month, compared with 3 months for those given aggressive treatment. Only two patients (aged 74 and 67) survived more than 2 years in complete remission (CR), both having been treated aggressively. We conclude that the prognosis for those over 60 years of age is extremely poor, but that for a small number of patients a useful prolongation of good quality life may be achieved. Age should not, by itself, be a bar to treatment intended to induce remission. Patients and their relatives should be made aware of the overall poor prognosis and advised of the therapeutic goals when decisions regarding management are being made.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Autologous bone marrow transplantation for high-grade lymphoid malignancy using melphalan/irradiation conditioning without marrow purging or cryopreservation. The Northern Regional Bone Marrow Transplant Group.

We report the safety and efficacy of 34 consecutive autologous bone marrow transplant (ABMT) procedures performed in adult patients with high-grade lymphoid malignancy after remission induction therapy. Fifteen patients with acute lymphoblastic leukemia (ALL) and six with high-grade non-Hodgkin's lymphoma (NHL) received pretransplant conditioning with intravenous (IV) melphalan and fractionated total body irradiation (TBI). Thirteen other patients with NHL were conditioned with melphalan alone, having previously received local involved field radiotherapy. Unmanipulated noncryopreserved autologous marrow was reinfused within 48 hours of harvesting. Engraftment occurred in all patients with medians of 10 days of neutropenia (neutrophils less than 0.5 x 10(9)/L), 4-day platelet transfusion requirement, 3 U packed RBC transfusion, and 18 days in hospital posttransplant. There were no procedure-related deaths. Actuarial disease-free survival in the 13 patients with ALL receiving autotransplant early in first remission is 48% with a median follow-up of 3 years. Two other ALL patients who had autotransplants after a period of maintenance therapy also remain in complete remission (CR). These results compare favorably with our 34% disease-free survival (DFS) in 15 allogeneic ALL transplant patients and 21% DFS in 19 patients on standard maintenance after a common induction schedule. No relapses have occurred in the 17 NHL patients transplanted in remission (median follow-up 2 years), but the two NHL patients who developed recurrent disease before ABMT died of progressive disease after temporary responses. We conclude that this method of ABMT results in rapid reengraftment with lack of toxicity and that the conditioning treatment used shows good efficacy against disease. It is applicable in high-grade lymphoid malignancy in first remission, and our results call into question the need for marrow purging in ALL and NHL patients transplanted in first remission.

Adult↗
PubMed1991

Immunopathology of early graft-versus-host disease--a prospective study of skin, rectum, and peripheral blood in allogeneic and autologous bone marrow transplant recipients.

The immunopathological appearances of skin and rectum in 64 autologous and allogeneic recipients were determined before and after bone marrow transplantation. Patients who developed acute graft-versus-host disease were biopsied as soon as a clinical diagnosis was made. At the same time peripheral blood samples were collected for comparative analysis. Immunohistological and morphometric techniques were employed using a panel of monoclonal antibodies to T lymphocytes and subsets, B lymphocytes, natural killer cells, macrophages, and Langerhans cells. A reduction in the CD4/CD8 ratio after BMT was seen in skin and rectal biopsies from both autologous and allogeneic recipients with or without GVHD. The same pattern was observed in blood samples taken at the same time. Langerhans cells were reduced in the skin in all patients after BMT, probably by the conditioning regimen. Only a few cells expressing activation or natural killer cell markers were present and there were no changes observed in the macrophage population. This study has provided no evidence to implicate either CD4- or CD8-positive T lymphocytes as the initiators of the cellular damage in acute GVHD. The distribution of lymphocyte subsets in the blood was similar to that in the tissues, suggesting that the tissue changes reflect the pattern of lymphocyte repopulation after BMT and may have little bearing on the pathogenesis of GVHD.

Adolescent↗
PubMed1991

Ocular complications of bone marrow transplantation.

Forty-one patients who had undergone bone marrow transplantation were examined. Nineteen (63%) of the 30 who had received fractionated total body irradiation (TBI) had cataracts in comparison with only 1 (9%) of the 11 non-irradiated patients. No significant differences in steroid therapy were demonstrated between these groups of patients. Dry eyes were observed in eight irradiated patients, seven of whom had preceding graft-versus-host disease. Superficial punctate staining of the bulbar conjunctiva was observed in 25 (83%) of the irradiated group and, in milder form, in five (45%) of the non-irradiated group. Our data suggest that the incidence of cataract following fractionated TBI is influenced not only by the total dose of radiation but also by its rate of administration (defined by midline tissue dose rate and fractionation schedule). In addition dry eyes and conjunctival staining may be exacerbated by TBI, though other aspects of conditioning may also be implicated.

Adult↗
PubMed1991

Transfemoral digital subtraction aortography. Are diluted high osmolar contrast media acceptable?

The ionic monomer, sodium diatrizoate at 150 mg I/ml (726 mosmol/kg) and the non-ionic monomer, iopamidol, diluted to the same iodine concentration but at 324.3 mosmol/kg, were randomly allocated to patients undergoing transfemoral intra-arterial digital subtraction angiography for lower limb peripheral vascular disease. The agents produced images of comparable quality and diagnostic efficacy. There were no significant differences between the media regarding sensations of pain and warmth. Minor neurological symptoms (headache and dizziness) occurred 7 times more frequently with the ionic monomer. There was a slight but temporary rise in plasma potassium one hour after injection of the ionic monomer but no evidence of appreciable intravascular haemolysis. The non-ionic monomer caused a slight fall in haemoglobin and haematocrit one hour after injection which is attributed to osmotic haemodilution. It is concluded that a diluted high osmolar contrast agent is an acceptable alternative to a low osmolar agent in transfemoral digital subtraction lower limb aortography.

Adult↗
PubMed1990

Virus infections in bone marrow transplant recipients: a three year prospective study.

Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.

Acyclovir↗
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↗
PubMed1989

The South Dakota Med-Fax network.

Health sciences librarians established a statewide medical information network in South Dakota to provide rural physicians with database access and rapid document delivery. A private grant funded equipment for interactive simultaneous remote searching (ISRS) and telefacsimile transmission, as well as for a coordinator for training and follow-up support. In less than one year, telefacsimile technology has become an integral part of library information transfer among sixteen network sites, and ISRS is gaining acceptance among physicians who lack local access to online databases.

Copying Processes↗
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

Histology of neuroblastoma involving bone marrow: the problem of detecting residual tumour after initiation of chemotherapy.

One hundred and eighty bone marrow trephine biopsies obtained during 68 staging procedures before and during treatment of 20 children with Stage IV neuroblastoma were reviewed. A primitive cell infiltrate with prominent fibrous stromal reaction and increased reticulin characterized the marrow at presentation. Once treatment had begun, primitive cells became difficult to find but fibrosis and a marked increase in reticulin persisted in most cases. Distortion in marrow architecture and the continuation of abnormal stromal reactions may reflect failure to eradicate tumour despite absence of detectable primitive cells. If current therapeutic options are to be assessed properly, uniformly accepted criteria to define continuance of marrow infiltration in children with neuroblastoma are needed. A scheme for classifying marrow histological appearances is presented which may prove to be of more value than a simple distinction between 'involved' and 'uninvolved'.

Adolescent↗