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Biomedical subjects

J A Amess

Publications and source records attributed to J A Amess.

At least 19 recordsLinked to original sources

Mitoxantrone and cytosine arabinoside as treatment for acute myeloblastic leukemia in older patients.

The majority of patients with acute myeloid leukemia (AML) are elderly, and their response to chemotherapy is poorer than that of younger patients. The combination of mitoxantrone (MTN) and cytosine arabinoside (Ara-C) is a possible alternative to an anthracycline/Ara-C combination for the treatment of AML in these patients. Of 52 older patients (> 59 years) referred over a 3.5-year period, 33 patients (age range 60-78 years, median 67 years) received MTN and Ara-C as therapy for newly diagnosed AML. MTN was administered at a dose of 12 mg/m2/day, intravenously, for 3 days (23 patients), or 10 mg/m2/day for 5 days (10 patients), and Ara-C at a dose of 100 mg/m2 twice daily, intravenously, for 7 days. Complete remission (CR) was achieved in 16/33 patients (48%). The median remission duration was 6 months (range 1-37 months). The median survival was 14 months for those who achieved CR compared with 9 months for those with resistant disease. Two patients remain in first CR after 13 and 37 months, but three patients died whilst receiving consolidation therapy. In selected elderly patients with AML, the combination of MTN and Ara-C provides an acceptable alternative to an anthracycline/Ara-C regimen, with a higher CR rate than historical controls. However, the CR rate and remission duration remain low compared with those of younger patients, supporting the need to investigate new approaches to treatment in this population.

Age Factors

Myelo-ablative therapy with peripheral blood progenitor cell (PBPC) support in patients with haematological malignancy.

BACKGROUND: Myelo-ablative therapy with peripheral blood progenitor cell (PBPC) support is increasingly being used in patients with haematological malignancy considered to be at high risk for recurrence. The results of this approach, in comparison with the previous experience at St. Bartholomew's Hospital (SBH) using autologous bone marrow transplantation form the basis of this report. PATIENTS AND METHODS: 42 patients (age range 18-63 years, median 42 years), deemed to have a poor prognosis with conventional therapy received myelo-ablative therapy with PBPC support. Diagnoses comprised: non-Hodgkin's lymphoma (NHL): 16 patients, Hodgkin's disease (HD): 9, Multiple Myeloma (MM): 12, and solid tumours (ST): 5. PBPC were mobilised using adriamycin: 35 mg/m2 i.v. on day 1 and etoposide 100 mg/m2 orally, days 1-5, followed by G-CSF: 5 micrograms/kg, subcutaneously, for a median of 7 days (range 6-9 days). RESULTS: A total of 67 PBPC collections were performed, 1 being 'sufficient' (i.e. mononuclear cells > or = 1.5 x 10(8)/kg and CD34+ cells > or = 1 x 10(6)/kg) in 21 of the 42 patients. The median time to haematological recovery following reinfusion of PBPC was 13 days for both neutrophils > 0.5 x 10(9)/l and platelets > 20 x 10(9)/l (ranges: 8-27, and 8-48 days, respectively) which is significantly shorter than for patients in the historical control group. Supportive care requirements were also significantly reduced, as was the duration of hospital stay i.e., median 19 days (range 12-73 days) compared with 29 days (range 9-180 days). CONCLUSION: These results confirm rapid blood count recovery following myelo-ablative therapy with PBPC support and the feasibility of this approach.

Adolescent

Measurement of activity of urea resistant neutrophil alkaline phosphatase as an antenatal screening test for Down's syndrome.

OBJECTIVE: To investigate the value of measuring maternal urea resistant neutrophil alkaline phosphatase activity as an antenatal screening test for Down's syndrome. DESIGN: Case-control study of blood samples collected at nine to 27 weeks of pregnancy. SETTING: Antenatal clinics in London and Oxford. PATIENTS: 72 Women whose fetuses had been diagnosed by amniocentesis or chorionic villus sampling as having Down's syndrome and 156 women whose fetuses did not have the syndrome. Only singleton pregnancies were studied. MAIN OUTCOME MEASURE: Activity of urea resistant neutrophil alkaline phosphatase measured cytochemically. RESULTS: The median enzyme activity in the index patients was 1.65 times the expected median for the controls at the same duration of pregnancy (p less than 0.0001; 95% confidence interval 1.56 to 1.74). A cut off value that identified the 5% of control patients with the highest activities yielded a rate of detection of Down's syndrome of 79% (95% confidence interval 70 to 89%). CONCLUSION: Activity of urea resistant neutrophil alkaline phosphatase is an effective maternal blood marker for Down's syndrome. Its use in antenatal screening could lead to a substantial improvement in the detection of this disorder. Before introducing the test into routine medical practice it will have to be automated so that it can be used on a large scale and is less subjective.

Adult

Observations on the haemopoietic response to critical illness.

Peripheral blood cytopenias are common in patients receiving intensive care, particularly in those with multiple organ failure. To assess the contribution of bone marrow hypoplasia in such patients 44 bone marrow samples from 24 patients under intensive care were studied by standard morphological techniques and by the granulocyte-macrophage colony forming cell (GM-CFC) assay. Frequently observed morphological abnormalities in the bone marrow included the following: (i) a reduction in overall cellularity in seven patients, with a progressive decrease in most patients studied sequentially; (ii) an increase in the number of actively phagocytic macrophages; and (iii) a disruption of normal bone marrow architecture with the accumulation of intercellular hyaluronic acid glycosaminoglycan. Mean GM-CFC growth was significantly reduced when compared with that in a group of normal controls. In four of five patients studied sequentially GM-CFC growth became subnormal in association with a reduction in bone marrow cellularity. Inhibitory serum factors were not identified. These morphological abnormalities are similar to the changes observed in gelatinous degeneration of the bone marrow. In both situations disruption of the haemopoietic microenvironment, with the accumulation of hyaluronic acid proteoglycan, may be an important factor in the inhibition of haemopoietic progenitor cell growth. The proliferation of macrophages, by the release of a variety of cytokines or reactive oxygen intermediates, may also be implicated in impaired haemopoiesis and the development of disordered erythropoiesis.

Adolescent

Erythromyeloid lineage fidelity is conserved in erythroleukaemia.

Blast cells from eight patients with erythroleukaemia and one with erythroid blast crisis of chronic myeloid leukaemia were studied for the co-expression of cell surface myeloid and erythroid markers, and the phenotype compared with that of erythroblasts from two patients with megaloblastic anaemia. The technique of dual indirect immunofluorescence was used with a panel of seven mouse monoclonal antibodies against well-defined myeloid antigens (CD11b, 13, 14, 15, 33 and HLA-DR) and a rat antibody, YTH89.1, specific for glycophorin A. No dual fluorescence, emanating from myeloid or erythroid lineage markers, was found to occur in either the neoplastic or non-neoplastic erythroid cells studied. These data support the hypothesis that lineage fidelity is conserved in leukaemia.

Anemia, Megaloblastic

Low field strength magnetic resonance imaging of bone marrow in patients with malignant lymphoma.

Detection of bone marrow infiltration by lymphoma with low field strength magnetic resonance imaging (MRI) has been assessed. Measurements of spin lattice relaxation time (T1) were made in 31 patients with lymphoma and compared with the results of bone marrow biopsy and with T1 measurements made on 90 healthy volunteers. The sensitivity of MRI was excellent in patients for whom the microscopic pattern of marrow infiltration was diffuse, but poor in those with microscopically focal infiltration.

Adult

Autosomal inheritance of sideroblastic anaemia.

Inherited sideroblastic anaemia is usually transmitted as an X-linked disorder (Losowsky & Hall 1965). We report a patient in whom family studies indicated autosomal inheritance, with direct transmission from father to son. The severe nature of the sideroblastic abnormality in the proband may be due to interaction between the sideroblastic trait and a single allele for idiopathic haemochromatosis.

Adult

Pancytopenia in a patient receiving home intravenous nutrition.

A patient is described who developed pancytopenia several months after home intravenous nutrition (IVN) was started following a major small bowel resection for volvulus. In the post-operative period his weight fell by about 15 kg to 45 kg. Bone marrow aspiration and leucokinetic studies were carried out which suggested that bone marrow failure was the cause of this patient's haematological abnormalities. Five of the 16 patients at St Mark's Hospital who are receiving home IVN were noted to have had transient neutropenia. In 3 of these patients significant weight loss was also noted in the few months preceding the development of neutropenia. It is suggested that there is an association between relative energy malnutrition and the development of the haematological abnormalities that have been observed. In the patient described here these abnormalities were prolonged.

Adolescent

Subtle abnormalities in the short arm of chromosome 11 in acute myeloid leukemia.

A series of four patients with small deletions of the short arm of chromosome #11 is presented. In two of these patients, deletion of 11p was the sole karyotypic abnormality. When compared with similar reported cases an association with FAB type M4 is apparent. Such cases may often be undocumented, because the deletions can be subtle. One patient with erythroleukemia shows an inversion of chromosome #11 involving band 11p15. Because the patients' fetal hemoglobin (HbF) became raised during the course of the disease, it is postulated that the hemoglobin beta chain gene at 11p15 may have been disrupted.

Adolescent

Post-transfusion purpura associated with anti-Baka and anti-PIA2 platelet antibodies and delayed haemolytic transfusion reaction.

The occurrence of post-transfusion purpura (PTP) in a 16-year-old girl with sickle/beta-thalassaemia is described. Clinically this was a typical case of PTP, but it was unusual serologically. Anti-Baka and anti-PIA2 platelet-specific antibodies were identified and the patient's platelets were typed as homozygous PIA1-positive and Baka-negative. The patient also developed red-cell, granulocyte and lymphocytotoxic antibodies in response to the blood transfusion and had a delayed haemolytic transfusion reaction.

Adolescent

Unusual myeloid leukaemia in patient with Hodgkin's disease.

An unusual case of leukaemia in a patient with Hodgkin's disease is described. The leukaemic blast cell population was typified by the presence of a substantial proportion of binucleate and multinucleate cells, many of which had the morphological features of Sternberg-Reed cells. The circulating and bone marrow blast cells were shown by immunophenotyping to be of myeloid origin.

Hodgkin Disease

Demonstration of lymphoid antigens in decalcified bone marrow trephines.

A panel of antibodies recognising lymphoid and epithelial antigens in formalin fixed, paraffin embedded sections was applied to a series of 54 bone marrow trephines decalcified by formic or edetic acids. Normal trephines and cases infiltrated by myeloid, lymphoid, and epithelial tumours were included. Patterns of reactivity were distinct and allowed the different diseases to be distinguished. All lymphoid tumours expressed leucocyte common antigen, with B cell tumours staining with MB1 and MB2, and T cell tumours staining with MT1 and UCHL1. T cell acute lymphoblastic leukaemia (ALL)/lymphoblastic lymphoma all stained with MT1, but some were negative with UCHL1. B cell ALL/lymphoblastic lymphoma also stained with MT1, but could be distinguished by its reactivity with MB1 and MB2. Reed-Sternberg cells did not stain with any reagent. Normal and neoplastic myeloid cells stained with MT1. Carcinomas stained with CAM 5.2 but were negative for lymphoid markers except MB2 staining in some cases. A case of neuroblastoma could be distinguished from ALL/lymphoblastic lymphoma by its lack of reactivity with all antileucocyte antibodies and its staining with antineurone specific enolase. Although not ideal, if used together, this panel of reagents may usefully be applied to routinely fixed and processed, decalcified bone marrow trephines.

Antibodies, Monoclonal

Bone marrow hypoplasia during intensive care: bone marrow culture studies implicating ranitidine in the suppression of haemopoiesis.

Two seriously ill patients with renal failure developed bone marrow hypoplasia and peripheral blood cytopenias during admission to an Intensive Care Unit (ICU). Both patients were being treated with ranitidine and, in both, there was evidence of drug accumulation. Serum from the patient with the highest concentration of ranitidine inhibited granulocyte-macrophage colony growth from normal bone marrow. The addition of ranitidine to cultures of normal bone marrow also produced a concentration-dependent inhibition of colony growth. Ranitidine should be used with caution in patients with renal failure where drug accumulation may seriously impair bone marrow function.

Aged

Passive potassium transport in human red cells.

The effect of procedures known to stimulate the volume-sensitive KC1 pathway has been studied in human red cells. This system is functional in young, but not mature cells and may mediate large fluxes in individuals with large fractions of reticulocytes. The pathway is apparently latent in mature cells, but may be unmasked by certain procedures suggesting that the transporter is not lost from the membrane during cell maturation.

Biological Transport