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Biomedical subjects

M E Beard

Publications and source records attributed to M E Beard.

At least 37 records · Page 2Linked to original sources
PubMed1991

The costs and benefits of bone marrow transplantation.

The average direct costs of performing a bone marrow transplant (BMT), including the subsequent year, was found to be NZ$27,074 for 43 consecutive transplants. In 29 BMTs a full two year period of follow up was available and a quality of life analysis was carried out on these patients. It was calculated that 59 quality adjusted life years (QALYs) had been gained by the BMT procedure at the time of analysis. By combining these two analyses the cost of each QALY gained by BMT is NZ$13,272. The relatively low cost of BMT is partly due to the extremely low annual costs in second and subsequent years post BMT. In our patients this cost amounted to $195 per year. The costs and benefits of BMT compare very favourably with other complex medical procedures.

Adult↗
PubMed1991

Erythrocyte sedimentation rates in the elderly: a community study.

One hundred and ninety-four elderly subjects living in the community were randomly selected in order to define a reference range for erythrocyte sedimentation rate (ESR) for this age group. Mean (S.D) values were 4.1 (2.9) mm in one hour and 7.2 (2.6) mm in one hour for men and women respectively. Values ranged from 0-44 mm in one hour. The ESR showed significant independent correlations with fibrinogen, haemoglobin (male and female) and albumin levels (male only). A new algorithm for determination of the upper limit of normal for age is proposed: Females ESR = Age/3 + 10 Male ESR = Age/3.

Age Factors↗
PubMed1991

A community study of vitamin B12 and folate levels in the elderly.

OBJECTIVE: To measure the prevalence of low serum vitamin B12, folate, and red cell folate levels and their relationship with other nutritional indices. DESIGN: Prospective survey of elderly subjects using radioisotope dilution assays. SETTING: Primary care medical center, Christchurch, New Zealand. PATIENTS: 257 elderly subjects (age 65 years and over), residing in their own homes or in residential homes, were randomly selected. Of these, 204 (79%) participated. The study population was comparable to the elderly population of New Zealand. MAIN OUTCOME MEASURES: Vitamin B12, serum, and red cell folate levels. RESULTS: The prevalence rates for low levels of serum vitamin B12, folate, and red cell folate were 7.3%, 1%, and 3.3%, respectively. The elderly cohort had lower vitamin B12 (P less than 0.001) but higher serum and red cell folate levels (P less than 0.001) than our normal reference range (age 18-65 years). Red blood cell folate levels showed positive correlations with nutritional indices and mental test scores. No correlations were found between vitamin B12 levels and diet or other nutritional indices. CONCLUSIONS: Low folate levels in older people living at home are infrequent findings. In contrast low vitamin B12 levels are more common. Poor diet and undernutrition may contribute to low folate levels, but these factors are less important for the low B12 levels found.

Aged↗
PubMed1991

Intranasal amphotericin B reduces the frequency of invasive aspergillosis in neutropenic patients.

PURPOSE: To retrospectively study the prophylaxis of invasive aspergillosis in neutropenic patients and to relate the frequency of this fungal disease to any causal or modifying factors that could be identified. PATIENTS AND METHODS: Between 1977 and 1988, 130 patients underwent 158 intensive treatment episodes to control acute leukemia, lymphoma, and aplastic anemia, and the frequency of complicating aspergillus infection was determined. RESULTS: Proven invasive aspergillus infections occurred in 22 cases, 12 of which were fatal. Invasive aspergillosis was suspected in a further 16 cases and all these patients recovered with amphotericin B treatment. Colonization by Aspergillus in the absence of clinically significant infection was seen in 31 treatment episodes. Invasive aspergillosis involved mainly the upper and lower respiratory tract and skin. Control of the infection was closely related to the control of the underlying disease, with subsequent return of normal marrow function and resolution of neutropenia. The incidence of aspergillus infection has decreased dramatically since 1985, most probably due to the introduction of intranasal amphotericin B. This occurred despite the persistence of aspergillus spores in the hematology ward air during the 1986 to 1988 period. CONCLUSION: Intranasal aerosolized amphotericin B may protect against invasive aspergillosis, even when neutropenic patients are cared for in conventional wards without HEPA filtration.

Administration, Intranasal↗
PubMed1991

Busulphan/cyclophosphamide conditioning for bone marrow transplantation may lead to failure of hair regrowth.

Following the introduction of bulsulphan and cyclophosphamide (BUCY) conditioning in our unit in 1987, a number of patients noted incomplete scalp hair regrowth following bone marrow transplantation (BMT). Between August 1987 and May 1989, 22 patients had undergone allogeneic or autologous BMT in our unit and we recalled for detailed assessment the 14 who were alive and well at least 6 months post grafting. Six patients had experienced incomplete hair regrowth of varying severity 7-27 months following BMT. All those affected had received BUCY conditioning and the four most severely affected were allogeneic BMT recipients. No patient had received any post-BMT chemotherapy or radiation. None of the patients had evidence of graft-versus-host disease. No laboratory test abnormalities distinguished the affected from the unaffected patients. Despite the relatively small number of patients, our results suggest that BUCY has caused permanent damage to the hair follicles of the affected patients. Prolonged alopecia may markedly impair the quality of life for long-term survivors of BMT and this unexpected complication also has significant medicolegal implications.

Adolescent↗
PubMed1990

D-aspartate oxidation by rat and bovine renal peroxisomes: an electron microscopic cytochemical study.

D-amino acid oxidase, a peroxisomal enzyme, and D-aspartate oxidase, a potential peroxisomal enzyme, share biochemical attributes. Both produce hydrogen peroxide in flavin-requiring oxidative reactions. Such similarities suggest that D-aspartate oxidase may also be localized to peroxisomes. Definitive identification of D-aspartate oxidase as a peroxisomal enzyme depends, however, on visualization at the electron microscopic level. Using incubation conditions shown to be specific for the enzyme in biochemical studies, this report extends the cytochemical localization of D-amino acid oxidase to bovine renal peroxisomes, and shows that D-aspartate can be oxidized by rat and bovine renal peroxisomes. An unexpected finding was the sensitivity of both D-amino acid oxidase activity (proline specific) and D-aspartate oxidase activity to inhibition by agents used in biochemical studies to discriminate between the two enzyme activities. Therefore, it is possible that, in the cytochemical system used in this study, (a) either D-proline and D-aspartate are substrates for only one enzyme or (b) the two enzymes have additional overlapping biochemical properties.

Amino Acid Oxidoreductases↗
PubMed1989

Treatment of hairy cell leukaemia with recombinant alpha interferon.

Eleven patients with progressive hairy cell leukaemia (three nonsplenectomised) were treated with recombinant alpha-2 interferon (Intron-A or Roferon-A) subcutaneously three times per week at a dosage of 3 x 10(6) units. Ten patients completed at least ten weeks of therapy and could be evaluated; one patient died of haemorrhage from severe thrombocytopenia after only three weeks treatment. Nine of the ten patients responded and all of these are regarded as good partial remissions (normalisation of all blood parameters but still discernible hairy cells in the marrow). Responding patients have all been followed for a median of two years and in one case 3 1/2 years since commencement of therapy. The patients are all transfusion independent and free of infection. We conclude that alpha-2 interferon therapy for progressive hairy cell leukaemia is effective therapy in both splenectomised and nonsplenectomised patients.

Adult↗
PubMed1989

Peroxisomal bifunctional enzyme deficiency.

Peroxisomal function was evaluated in a male infant with clinical features of neonatal adrenoleukodystrophy. Very long chain fatty acid levels were elevated in both plasma and fibroblasts, and beta-oxidation of very long chain fatty acids in cultured fibroblasts was significantly impaired. Although the level of the bile acid intermediate trihydroxycoprostanoic acid was slightly elevated in plasma, phytanic acid and L-pipecolic acid levels were normal, as was plasmalogen synthesis in cultured fibroblasts. The latter three parameters distinguish this case from classical neonatal adrenoleukodystrophy. In addition, electron microscopy and catalase subcellular distribution studies revealed that, in contrast to neonatal adrenoleukodystrophy, peroxisomes were present in the patient's tissues. Immunoblot studies of peroxisomal beta-oxidation enzymes revealed that the bifunctional enzyme (enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase) was deficient in postmortem liver samples, whereas acyl-CoA oxidase and the mature form of beta-ketothiolase were present. Density gradient centrifugation of fibroblast homogenates confirmed that intact peroxisomes were present. Immunoblots of fibroblasts peroxisomal fractions showed that they contained acyl-CoA oxidase and beta-ketothiolase, but bifunctional enzyme was not detected. Northern analysis, however, revealed that mRNA coding for the bifunctional enzyme was present in the patient's fibroblasts. These results indicate that the primary biochemical defect in this patient is a deficiency of peroxisomal bifunctional enzyme. It is of interest that the phenotype of this patient resembled neonatal adrenoleukodystrophy and would not have been distinguished from this disorder by clinical study alone.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1989

Inhibition of non-MHC-restricted cytotoxicity by CD45 but not CD3 monoclonal antibodies in patients with large granular lymphoproliferative disease.

Nine patients with a lymphoproliferative disorder characterized by a persistent expansion of large granular lymphocytes (LGL) and an increased proportion of cells labelling with natural killer (NK) and T cell markers were identified. The six patients with an expansion of alpha beta CD3/TcR positive cells were shown to have rearranged T cell receptor (TcR) genes whereas three patients whose LGL lacked CD3/alpha beta TcR on the surface had no beta TcR rearrangement detected. Eight of the nine patients were shown to exhibit non-MHC-restricted cytotoxic activity against K562; this activity was inhibited by CD45 and CD45-associated monoclonal antibodies known to inhibit normal non-MHC-restricted cytotoxicity but not specific MHC-restricted cytotoxic T cell activity. In contrast, the CD3 monoclonal antibody OKT3 did not inhibit but redirected LGL non-MHC-restricted cytotoxicity against K562. Following modulation of the CD3 molecule, the LGL were still capable of cytolysis of K562 targets, but additional OKT3 could no longer redirect cytolysis. The data indicate that the CD3/TcR complex on the LGL clones in patients with large granular lymphoproliferative disease is not the receptor for antigen on K562 cells, although it retains functional capabilities. Thus the CD3/TcR positive subset appears to have bipotential cytotoxic characteristics involving additional unique receptors for non-MHC-restricted cytotoxicity.

Adult↗
PubMed1988

Peroxisomes in pigment epithelium and Müller cells of amphibian retina possess D-amino acid oxidase as well as catalase.

In this paper we identify peroxisomes in Müller cells and retinal pigment epithelial cells of Rana pipiens and Xenopus laevis by virtue of their content of cytochemically stainable catalase. These organelles have the form of an extensive, branched system of tubules in the retinal pigment epithelium and appear as discrete ovoid structures in the Müller cells. In both the pigment epithelium and the Müller cells a second peroxisomal enzyme, D-amino acid oxidase, can be detected in the same structures as catalase by means of a cerium-based cytochemical staining procedure. This oxidase is active only against nonpolar and polar, uncharged D-amino acids.

Animals↗
PubMed1988

Abnormal chromosome 16 in clonogenic eosinophils from a case of acute myeloid leukemia (FAB,M2).

A case of acute myeloid leukemia (AML, FAB M2) is described in which the leukemic karyotype showed several numerical and structural cytogenetic abnormalities including an abnormal chromosome 16 with breakpoint at band q22, monosomy for chromosomes 5 and 7, and a single pair of double minute chromosomes. There was no patient history of treatment for a previous malignancy or occupational exposure to mutagens. Bone marrow eosinophilia was seen at presentation for refractory anemia with excess blasts in transformation and when AML was diagnosed. When bone marrow buffy coat cells were cultured in soft agar in the presence of colony stimulating factor, 19% of the colonies and 20% of the clusters were of eosinophils. Cytogenetic examination of pooled eosinophil colonies showed the marker chromosomes that identified the leukemic population.

Bone Marrow↗
PubMed1988

Essential thrombocythaemia and the Philadelphia chromosome.

Six adult patients presented with clinical features of essential thrombocythaemia. Five of the patients, although Ph-positive, have maintained these features without evidence of leukaemia; in one case for 9 years. A sixth patient developed leukaemic blast crisis following a persistently high platelet count over 4 years. Her cells were Ph-negative, but hybridization of gene probes to chromosomes in situ and to leukaemic DNA showed that the abl oncogene had moved to the breakpoint cluster region (bcr) on the normal chromosome 22. This patient has the same molecular gene change as occurs in some cases of Ph-negative chronic myeloid leukaemia (CML) whose leukaemic cells likewise show no evidence of chromosomal translocation. Molecular studies are essential for the correct diagnosis of these patients. The Ph genomic lesion appears to have a range of leukaemic expression which includes thrombocythaemia as well as chronic myeloid leukaemia and acute lymphatic leukaemia.

Adult↗
PubMed1988

The tissue distribution of the 3 alpha-fucosyl-N-acetyl lactosamine determinant recognized by the CD15 monoclonal antibodies CMRF-7 and 27.

Two monoclonal antibodies, CMRF-7 and 27, which react with cells of the granulocytic series, were obtained from hybridomas cloned from separate fusions. Biochemical studies indicate that both antibodies are of the CD15 group and react with the antigenic determinant 3 alpha-fucosyl-N-acetyl lactosamine (hapten X) expressed on some glycolipids and several different granulocyte glycoproteins with a wide range of molecular weights. The antigen was found on some promyelocytes and more differentiated granulocytes, including neutrophils and some eosinophils, but not basophils. Monocytes, lymphocytes, and erythrocytes were negative for CMRF-7 but neuraminidase treatment revealed "cryptic" sites on monocytes and some lymphoid cells. The antibody CMRF-7 reacted with the majority of acute myeloid leukemia blasts in the FAB categories M2-M5 but less frequently with M1 blasts and was positive with only 5/43 acute lymphoid leukemias. Immunoperoxidase staining of other normal human tissues indicates that this determinant is found on a range of epithelial cells in skin, the gastrointestinal tract and the genitourinary system. In addition some parts of the central nervous tissue and some endocrine organs stained with these antibodies.

Antibodies, Monoclonal↗
PubMed1987

Sustained complete remission in Richter's syndrome.

Richter's syndrome is the development of an aggressive diffuse lymphoma in chronic lymphatic leukemia (CLL) and is associated with a poor prognosis. A patient with CLL developed Richter's syndrome, which responded to intensive chemotherapy. Spontaneous regression of CLL in blood and marrow was observed at the onset of Richter's syndrome. The patient remained in complete remission from the lymphoma 4 years after the completion of treatment, and there was no evidence of CLL.

Antineoplastic Combined Chemotherapy Protocols↗