Interferon induced severe digital ischaemia in chronic myeloid leukaemia--successful treatment using ketanserin.
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Adult↗
Biomedical subjects
R J Cuthbert
Publications and source records attributed to R J Cuthbert.
A study on dust emission, particle size distribution and formaldehyde concentration during machining of medium density fibreboard.
A study to characterise the quantity, particle size distribution and morphology of dust created during the machining of MDF was carried out. Four different types of MDF boards were included in this study, including a 'zero-formaldehyde' board that contains isocyanate-based resin, rather than urea-formaldehyde resin. In addition, natural softwood (pine) and natural hardwood (oak) were included in the study, for comparison with MDF. The results show that in general, the dust generated by machining MDF is comparable in terms of particle size distribution and morphology with the dust generated by similarly machining hardwood or softwood. The quantity of dust generated during sanding is higher for sanding MDF compared with sanding either hardwood or softwood. However, for sawing there is no significant difference between MDF and natural woods, in terms of the quantity of dust generated. Free formaldehyde in the air was less than 0.17mg m(-3) during machining of the Class B (higher formaldehyde potential) MDF board. There was no measurable isocyanate in the dust generated from the boards.
Air Pollutants, Occupational↗
Transfusion in the management of patients with megaloblastic anaemia.
Transfusion has been associated with significant morbidity and mortality in megaloblastic anaemia (MA). This retrospective study was undertaken to examine the usefulness of transfusion in the management of MA. Fifty-two patients with MA were identified. Of the 20 transfused patients 13 were treated with diuretics and six with potassium supplements. The mean haemoglobin (Hb) of the transfused group was 6.5 g/dl (range 4.8-10.4 g/dl), and of the 32 non-transfused patients 10.5 g/dl (range 5.6-17.0 g/dl). The Hb and packed cell volume (PCV) were significantly lower in the transfused group. Only two of 32 non-transfused group were given potassium supplements. In this small group of patients with MA, transfusion appeared to be safe and no complications of transfusion were identified. However, advice was not being followed. We would suggest that, although transfusion has a minor role in the management of MA, consideration must be given to the general hazards of transfusion.
Anemia, Megaloblastic↗
Functional hyposplenism following allogeneic bone marrow transplantation.
AIMS: To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS: Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS: Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION: These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT.
Adolescent↗
Allogeneic bone marrow transplantation for severe aplastic anemia: the Vancouver experience.
We report a retrospective analysis of the experience of a single centre in treating severe aplastic anemia (SAA) with allogeneic bone marrow transplant (BMT). Between 1982 and 1992, we transplanted 21 patients with SAA (14 males, 7 females); median age at BMT was 15 y (range 2-40 y); median time from diagnosis of SAA to BMT was 29 d (range 6 d-5.5 y). Thirteen patients had received multiple transfusions before BMT. Patients were conditioned with cyclophosphamide 50 mg/kg for 4 d, +/- total body irradiation 300-500 cGy as a single fraction; 1 patient received total nodal irradiation (750 cGy) plus antithymocyte globulin. Sixteen patients received bone marrow from human leucocyte antigen (HLA)-identical siblings, 3 from haplo-identical parents, and 2 from unrelated volunteer donors; graft-versus-host disease (GVHD) prophylaxis was variable. Three patients failed to fully engraft following BMT; 2 achieved successful engraftment following a second BMT. Six of 20 evaluable patients (30%) developed grade II-IV acute GVHD, of whom 3 died; 3 patients developed limited and 5 patients (31%) developed extensive chronic GVHD, of whom 1 died. Fourteen patients (67%) are alive and well following BMT with a median follow-up of 6 y (range 2.1-11 y). Survival was superior in patients receiving sibling-donor BMT (75%) compared with those receiving parent- or unrelated-donor BMT (40%). We conclude that allogeneic BMT remains an important mode of treatment for SAA, but long-term survival remains limited by graft failure and GVHD.
Adolescent↗
Intensive treatment of renal failure in patients with myeloma.
We have reviewed our experience in the management of myeloma patients who present with features of severe renal impairment, to examine the role of intensive treatment of the renal failure, and to assess the role of renal biopsy. Between March 1983 and August 1991, 16 patients, who were subsequently diagnosed as having myeloma, presented to the Department of Renal Medicine for investigation of renal failure; nine with symptoms of uraemia and seven with pneumonia, bone pain, emphysema, or ischaemic heart disease. Renal biopsy was performed on 14 patients. Eleven patients had myeloma cast nephropathy, two of whom had concurrent hypertensive nephropathy, two patients had light chain deposition disease, and one patient had interstitial nephritis. Renal function improved in six patients with aggressive rehydration, but three of them subsequently required dialysis. In all 11 patients required dialysis, two short-term and nine long-term. Seven patients were given conventional melphalan and prednisolone and nine patients received VAMP as induction cytotoxic chemotherapy. Five of the VAMP sub-group received interferon alpha 2b as maintenance therapy. The median renal survival was five months (range 0-36 months) and median overall survival was 20 months (range 1-54 months). We conclude that intensive treatment, including dialysis, in myeloma patients with renal failure may result in survival durations approaching those of unselected myeloma patients, and a significant proportion will enjoy a reasonable quality of life.
Adult↗
Stevens-Johnson syndrome associated with methotrexate treatment for non-Hodgkin's lymphoma.
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Antineoplastic Combined Chemotherapy Protocols↗
Immunological studies in HIV seronegative haemophiliacs: relationships to blood product therapy.
Immunological studies were performed on a group of 44 haemophilia A and 15 haemophilia B patients who were treated exclusively with blood products manufactured by the Scottish National Blood Transfusion Service (SNBTS). All patients were HIV seronegative throughout the study. Of the haemophilia A patients 14 (32%) had CD4+ lymphocyte subset counts less than or equal to 0.5 x 10(9)/l, compared with one (6%) haemophilia B patient and four (8%) controls. The percentage of activated T cells was greater than 5% in 19/33 (57%) with haemophilia A, 5/9 (55%) haemophilia B and 14/50 (28%) of control subjects. beta 2 microglobulin values greater than or equal to 2.0 mg/l were observed in 19 (43%) haemophilia A and four (26%) haemophilia B patients, compared with one (2%) control. No significant increases in serum interleukin-2 receptor concentrations were observed in 15 haemophilia A and one haemophilia B patients. Significantly elevated levels of IgG, IgM and IgA were observed in the haemophilia A group, but elevation of immunoglobulins was restricted to the IgG class in the haemophilia B group. Of the haemophilia A patients 16/30 (53%) and 6/11 (54%) haemophilia B patients had depression of cell-mediated immunity (CMI) as assessed by delayed-type hypersensitivity responses to intradermally injected recall antigens. There was no correlation between factor VIII or factor IX usage and changes in lymphocyte subsets, beta 2 microglobulin, and immunoglobulin levels. There was, however, a strong correlation between annual factor VIII usage and the degree of depression of CMI for those with haemophilia A but not for those with haemophilia B. No correlation between alterations in the immune parameters and disturbance of liver function tests was observed in either haemophilia A or haemophilia B patients. We conclude that alloantigen or non-HIV viral exposure due to repeated administration of factor concentrates brings about alterations in the immune response, and that these changes are more marked following exposure to intermediate purity factor VIII compared with factor IX concentrate.
Factor IX↗
Anti-interleukin-2 receptor monoclonal antibody (BT 563) in the treatment of severe acute GVHD refractory to systemic corticosteroid therapy.
Fourteen patients with corticosteroid-resistant acute GVHD were treated with a murine monoclonal antibody to the pp55 interleukin-2 (IL-2) receptor (MoAb BT 563). Nine of the 14 patients had also failed Xoma-Zyme-H65 as GVHD prophylaxis and/or treatment. Seven patients had received HLA-matched sibling donor bone marrow transplants, five had received HLA-matched transplants from unrelated volunteer donors, and two had received one-antigen mismatched transplants from unrelated volunteer donors. At the time of MoAb BT 563 therapy, the overall clinical grading of acute GVHD (Seattle grading system) was as follows: grade II--one patient, grade III--four patients, and grade IV--nine patients. MoAb BT 563 was administered as a short iv infusion of 5 mg daily for 10 doses, followed by 5 mg on alternate days for a further five doses. A complete response (CR) was observed in four patients (28%), and a partial response (PR) in four patients (28%). All four complete responders were treated within 28 days of first onset of grade > or = II acute GVHD. Four patients (three CR, one PR) remain alive. One complete responder subsequently died from chronic GVHD. MoAb BT 563 administration was well tolerated in all 14 patients; no significant toxicity was observed. We conclude that MoAb BT 563 directed against the IL-2 receptor on activated T lymphocytes may be useful in treating corticosteroid-resistant acute GVHD if given early, but that it is of limited value in attempting to rescue patients with far-advanced refractory acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Cortex Hormones↗
Determinants of HIV disease progression: six-year longitudinal study in the Edinburgh haemophilia/HIV cohort.
Markers of immune function present before infection may determine the subsequent course of disease in HIV-infected individuals. In 1983, we measured immune function in a group of haemophiliacs in Edinburgh. In 1984, 18 of these patients became infected with HIV-1 from contaminated factor VIII. We have followed-up these patients since their seroconversion. The rate of disease progression, as assessed by the appearance or not of AIDS symptoms or signs within five years of seroconversion, was related both to the concentration of total plasma IgM before exposure to infection and to the pattern of specific IgM and IgA anti-HIV response around the time of IgG seroconversion. Disease progression also correlated with concentrations of plasma interleukin-2 receptor (a marker of lymphocyte activation) and with the number and percentage of circulating DR + ve (activated) T cells. Our findings show that the extent of host immune reactivity, which may be genetically determined, is a powerful factor in the pathogenesis of HIV-associated disease.
Acquired Immunodeficiency Syndrome↗
Treatment of acute myeloid leukaemia in a renal allograft recipient: implications of cyclosporin immunosuppressive treatment.
The clinical effects of cyclosporin were evaluated during cytotoxic treatment in a 61 year old man with acute myeloid leukaemia. He had required a renal transplant 18 months before presenting with acute myeloid leukaemia (FAB subtype M4). He had received cyclosporin 3.5-4.0 mg/kg daily to maintain a plasma cyclosporin concentration of 75-150 ng/ml. Cyclosporin was continued during induction chemotherapy with daunorubicin, cytarabine, and 6-thioguanine (DAT). He had fever and oropharyngeal candidiasis that was unresponsive to anti-bacterial drugs but responsive to systemic amphotericin. Bone marrow examination 14 days after chemotherapy showed complete haematological remission. Subsequently he tolerated consolidation treatment with DAT with no serious complications. Unfortunately he developed fatal septicaemia following a second consolidation with mitozantrone and cytarabine. Inhibition of P-glycoprotein activity by cyclosporin may not significantly increase the toxicity of aggressive chemotherapeutic regimens, and as benefit may be achieved by this approach further clinical evaluation is justified.
Antineoplastic Combined Chemotherapy Protocols↗
Five year prospective study of HIV infection in the Edinburgh haemophiliac cohort.
OBJECTIVE: To identify measures of immune state that reflect the course of HIV related disease in order to predict deterioration of symptoms and assess response to treatment. DESIGN: Five year longitudinal clinical and laboratory study. SETTING: Regional haemophilia centre, university virology laboratory, and Medical Research Council laboratory. PATIENTS: 32 Patients with haemophilia A exposed to a single batch of HIV contaminated factor VIII concentrate from the Scottish National Blood Transfusion Service in 1984 who were followed up regularly in Edinburgh (31) or abroad (one). MAIN OUTCOME MEASURES: Counts of circulating T cell subsets (CD4 and CD8); plasma beta 2 microglobulin, neopterin, and IgA concentrations; and delayed type hypersensitivity to multiple skin test antigens. RESULTS: 18 Patients who seroconverted after exposure had received significantly more contaminated factor VIII than the 14 who did not (mean 43 (range 9-109) v 15 (3-30) phials, p less than 0.01). The two groups were not distinguishable by other criteria before exposure. The group that seroconverted subsequently showed a progressive fall in mean circulating CD4 lymphocytes and an increase in plasma beta 2 microglobulin and neopterin concentrations. From 1987 patients in this group also showed an increase in mean circulating CD8 lymphocytes and in plasma IgA concentration, neither of which was seen in patients who did not seroconvert. Patients with HIV antibody who developed Centers for Disease Control category IV symptoms within five years after infection showed more extreme changes in all measures, except CD8 lymphocyte count, than those whose symptoms remained in categories II and III. Skin test reactivity declined to barely detectable levels in all patients positive for HIV antibody. CONCLUSIONS: Serial estimates of circulating CD4 lymphocytes and of plasma beta 2 microglobulin concentration are the most reliable measures of disease progression; of these, beta 2 microglobulin concentration seems to be the better predictor of impending serious symptoms. High IgA concentrations reflect rather than predict disease state. Individual variation in most measures is such that a wide range of measurements should be used in assessing the effects of trial treatment in HIV infected patients without symptoms.
Adolescent↗
Prognostic significance of activation and differentiation antigen expression in B-cell non-Hodgkin's lymphoma.
Immunophenotyping shows heterogeneity of expression of activation and differentiation antigens in B-cell non-Hodgkin's lymphoma (NHL). To investigate whether antigen expression correlates with clinical behaviour we have studied the clinical presentation and follow-up of a series of 111 B-cell lymphomas previously phenotyped for a panel of antigens including CD groups 5, 9, 10, 21, 23, 25, 30, 38, 4F2 antigen, and transferrin receptor. CD antigens 5, 10, and 23 were expressed significantly more often by low grade lymphomas whereas CD38, 4F2 antigen, and transferrin receptor were more often expressed by high grade lymphomas. There was a significant correlation with survival and age, stage at presentation, histological grade, and expression of 4F2 antigen and transferrin receptor but not with the other antigens studied. 4F2 antigen and transferrin receptor may identify a poor prognostic group of cases in low grade lymphoma but we conclude that phenotyping B-cell NHL for many of the antigens expressed at various stages of B-cell differentiation and activation does not provide clinically useful information in addition to that obtained from standard histological classifications.
Antigens, CD↗
Human immunodeficiency virus detection: correlation with clinical progression in the Edinburgh haemophiliac cohort.
HIV p24 antigenaemia and virus detection in cultures of peripheral blood lymphocytes were examined in 16 of 18 haemophiliacs infected with HIV by a single batch of Scottish National Blood Transfusion Service factor VIII concentrate. Six (38%) had p24 antigenaemia and 11 (69%) had positive lymphocyte cultures. All seven patients with serious HIV disease (CDC group IV) had positive lymphocyte cultures whereas four (57%) had p24 antigenaemia. Four of nine (44%) patients with asymptomatic HIV disease (CDC groups II and III) had positive cultures and two (22%) had p24 antigenaemia. Twenty-eight of 36 samples from the symptomatic group were HIV culture positive compared with nine of 30 samples from the asymptomatic group (P less than 0.001). None of 14 antibody negative haemophiliacs who also received the implicated batch of factor VIII had p24 antigenaemia or positive HIV cultures. The ability to detect HIV in cultured lymphocytes correlates with the clinical severity of HIV disease in this cohort.
AIDS Serodiagnosis↗
Central nervous system involvement in haematological malignancies.
We have reviewed our experience of central nervous system (CNS) involvement in 540 patients with lymphoma or acute leukaemia treated at the Royal Infirmary of Edinburgh between 1979 and 1987. CNS invasion is a significant problem in acute lymphoblastic leukaemia but may well respond to treatment, while in acute non-lymphoblastic leukaemia this complication occurs too infrequently to justify routine CNS prophylaxis. CNS involvement in Hodgkin's disease or non-Hodgkin's lymphoma (NHL) of low-grade malignancy was uncommon, exclusively of the extradural variety, and did not appear to alter the ultimate prognosis. Diffuse leptomeningeal involvement occurred with significant frequency in more aggressive NHL, often while the disease was in systemic remission or during remission induction. The prognosis for leptomeningeal disease or intracranial mass lesions was extremely poor and some form of CNS prophylaxis may be justified in aggressive NHL.
Acute Disease↗
HLA haplotype A1 B8 DR3 as a risk factor for HIV-related disease.
Of 32 patients exposed to a single batch of factor VIII contaminated with human immunodeficiency virus (HIV), 18 became antibody positive. Serial T cell subset analyses over the succeeding four years have shown a progressive decline in circulating T4 cells in those 18 but no change in the 14 who remain seronegative. 2 of the seroconverters have died and a further 7 have symptoms attributable to HIV infection. In the group as a whole, the HLA haplotype A1 B8 DR3 was weakly associated with an increased risk of seroconversion on exposure to the virus while, in those who seroconverted, it was strongly associated with a rapid decline in T4 cells and development of HIV-related symptoms within four years of infection.
Adult↗
DDAVP shortens the bleeding time in Bernard-Soulier syndrome.
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Adult↗
Efficacy of heat treatment of factor VIII concentrate.
Two batches of heat-treated factor VIII concentrate were found to contain anti-HIV-positive plasma donations. The batches were dry-heat-treated at 68 degrees C for 2 and 24 h, respectively. No HIV seroconversions occurred in 13 susceptible haemophiliacs receiving a total of 540 bottles of these factor VIII preparations.
Factor VIII↗