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Biomedical subjects

A C Newland

Publications and source records attributed to A C Newland.

At least 19 recordsLinked to original sources
PubMed1992

Expression of functional antigens on neutrophils. Effects of preparation.

We have studied how different conditions of cell labelling and isolation affect the expression of five functional antigens on neutrophils from healthy subjects. Fluorescein isothiocyanate conjugated (FITC) antisera specific for the C3bi receptor CR3 (CD11b), aminopeptidase N (CD13), the LPS:LPS binding protein receptor (CD14) and the receptors for human IgG (Fc gamma RII CDw32 and Fc gamma RIII CD16) were incubated with (i) unfixed whole blood at 4 degrees C and at room temperature (RT, approximately 20 degrees C), and the leukocytes prepared for analysis using the Coulter Q-Prep system, (ii) leukocytes which had obtained following the removal of erythrocytes from whole blood by dextran sedimentation and which had been washed or left unwashed at RT, and (iii) leukocytes which had been prepared from whole blood that had been formaldehyde fixed immediately following venesection. The amount of fluorescence associated with the cells was determined by flow cytometry. The expression of CD14 was low under all conditions. However the expression of CD11b, CD16 and CDw32 was significantly higher (p less than 0.05) on neutrophils obtained by dextran sedimentation (n = 4) than on cells which had been fixed with formaldehyde ex vivo; the increase in expression was even greater if the cells had been washed. In contrast, the expression of CD13 on formaldehyde fixed cells was higher than on cells which had been labelled at 4 degrees C or at room temperature and was similar to or slightly lower than that on cells obtained by dextran sedimentation. Increasing the time between 10 and 60 min for which the whole blood was incubated with antisera at RT or at 4 degrees C, resulted in progressive increases in the expression of CD11b and CD13. When neutrophils which had been obtained by dextran sedimentation were incubated with unlabelled antibodies to CD16 or CDw32 and FITC labelled antibodies to CD11b there was a marked increase in the expression of CD11b. Altogether these findings indicate that the analysis of functional molecules on neutrophils (which may be rapidly up-regulated during activation) should be performed under clearly defined and controlled conditions. Dual fluorescence studies may, in some circumstances, produce misleading results.

Analysis of Variance↗
PubMed1992

Continuous intravenous infusion of high-dose recombinant interleukin-2 for acute myeloid leukaemia--a phase II study.

A group of 13 patients with acute myeloid leukaemia of differing disease status were treated with continuous intravenous infusion of high-dose recombinant interleukin-2 (rIL-2). There was up-regulation of the cellular cytotoxic functions in all these patients following the rIL-2 therapy, with increase in the natural killer (NK) activity, lectin-dependent cellular cytotoxicity, induction of cytotoxicity-linked cytoplasmic serine esterase and lymphocyte activation. However, the clinical response to rIL-2 in these patients was disappointing, especially in patients treated in frank relapse. Although 1 patient treated in early second relapse achieved a third complete remission, the duration of the remission was brief and lasted only 6 months. Adverse reactions among these patients were common. Whether or not lymphokine-activated killer cells are needed to improve the response rate over rIL-2 alone in these patients deserves further investigation.

Adult↗
PubMed1992

Teicoplanin plus ciprofloxacin versus gentamicin plus piperacillin in the treatment of febrile neutropenic patients.

Teicoplanin plus ciprofloxacin was compared with gentamicin plus piperacillin for the empirical treatment of fever in 80 neutropenic patients. A favourable response was seen in 78% of patients receiving teicoplanin plus ciprofloxacin and in 49% receiving gentamicin plus piperacillin (p less than 0.05). When microbiologically documented episodes were analysed separately, the response to teicoplanin plus ciprofloxacin was favourable in 81% of patients whereas only 35% responded favourably to gentamicin plus piperacillin (p = 0.034). Gram-positive organisms accounted for 76% of bacterial isolates, Staphylococcus epidermidis being the most common pathogen. Ten of 12 (83%) Staphylococcus epidermidis infections resolved when treated with teicoplanin plus ciprofloxacin as compared with 2 of 8 (25%) treated with gentamicin plus piperacillin. Teicoplanin is at least as effective as gentamicin plus piperacillin in the empirical treatment of febrile neutropenic patients and may be more effective in situations where gram-positive organisms are prevalent. The high incidence of gram-positive infections in our unit justifies the use of an agent with specific activity against gram-positive organisms in the first-line antibiotic regimen.

Bacterial Infections↗
PubMed1992

The anti-leukaemic effects and the mechanism of sodium selenite.

The anti-proliferative effects of selenium were studied both in vivo and in vitro. At a selenium concentration of 0.6 micrograms/ml, cells from patients with ALL-L1, L2 and AML-M1, M3 and M5 were more sensitive than cells from patients with CML. Cells from patients with AML-M2, CLL and leukaemic lymphoma were least sensitive. Normal bone marrow or peripheral blood cells were not sensitive to selenium at this concentration. In the mouse leukaemia models (L797, L615, L7712), the sensitivity of leukaemic cells were: L797 (93% cytotoxicity) greater than L615 (49.7% cytotoxicity) greater than L7712 (4.4% cytotoxicity). Sodium selenite injected i.p. increased the longevity of L797-inoculated mice. Administration of 40 micrograms selenium daily for 7 days resulted in a significant increase in the longevity of mice inoculated with 10(5) L797 cells. However, no remarkable increase of the longevity was observed in either L615- or L7712-inoculated mice after treatment with sodium selenite for 7 days. Treatment of the HL-60 leukaemic cell line with selenium caused a dose- and time-related decrease in DNA, RNA and protein syntheses as measured by [3H]-thymidine, [3H]-uridine and [3H]-leucine uptake respectively. The inhibitory effect of selenium on DNA synthesis was reversed when selenium was removed from the medium, demonstrating that selenium-induced inhibition of DNA synthesis was due to interference with DNA biosynthesis rather than DNA template damage. These results suggest that the anti-leukaemic effect of sodium selenite is associated with inhibition of DNA replication, transcription and translation.

Animals↗
PubMed1992

Functional significance of induction of differentiation in human myeloid leukaemic blasts by 1,25-dihydroxyvitamin D3 and GM-CSF.

We studied the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and granulocyte-macrophage colony stimulating factor (GM-CSF) on monocytic differentiation of the U937 leukaemic cell line and blasts from patients with AML. 1,25(OH)2D3 and GM-CSF synergistically increased functional and phenotypic aspects of differentiation in the U937 cell line. In addition, the effective concentration of 1,25(OH)2D3 was reduced by up to 100 times in the presence of GM-CSF. GM-CSF alone had little differentiation-inducing effect on AML blasts. 1,25(OH)2D3 induced CD14 antigen expression in 67% AML blast populations and increased functional activation in 36%. 1,25(OH)2D3 and GM-CSF in combination cooperated to further induce CD14 antigen expression in one third of blast populations, while having no further effect on function. Failure to induce functionally effective levels of FcRII antigen on AML blasts following stimulation with 1,25(OH)2D3 and GM-CSF may account for the lack of functional activation.

Acute Disease↗
PubMed1992

The significance of aminopeptidases and haematopoietic cell differentiation.

Aminopeptidases are a group of enzymes found on the cell surface and in the cytoplasmic compartments of many peripheral blood cell types and their progenitors. Their functional roles include the hydrolysis of several biologically active peptides and growth factors and some have proved to be of diagnostic and prognostic value in leukaemia. These enzymes may also be found in serum as a consequence of non-haematopoietic related diseases and so have been used as indicators of liver damage. Haematopoietic cells in the bone marrow go through a process of growth and differentiation before being released into the peripheral circulation where they fulfill many functional roles. The enzyme activities of some aminopeptidases have been shown to modulate the growth of these cells. In addition, the activities of these enzymes themselves can be regulated by haematopoietic growth factors. However, the mechanisms that regulate their expression and activity are not fully understood. In this report the current literature has been reviewed for evidence of expression, regulation and clinical significance.

Aminopeptidases↗
PubMed1992

Prospective randomised study of double hemi-body irradiation with and without subsequent maintenance recombinant alpha 2b interferon on survival in patients with relapsed multiple myeloma.

Immediately before first hemi-body irradiation, 59 patients with relapsed multiple myeloma were randomised to receive or not to receive subsequent alpha-2b interferon maintenance. 13 patients (22%) [8 of 31 (26%) controls, 5 of 28 (18%) in the interferon arm] received single hemi-body irradiation alone due to progressive disease and/or persistent cytopoenias following the initial procedure. Mean time between upper and lower hemi-body irradiation was 69 days (range 35-294). Of 23 patients randomised to receive interferon and completing double hemi-body irradiation, 15 (65%) achieved peripheral blood counts adequate to allow interferon administration as per study criteria commencing at a mean 116 days (61-241) from time of study entry. The mean period of interferon therapy, starting at a mean 65 days (26-160) post second hemi-body irradiation, is 16.4 months (2-33.5). There was no significant difference in median survival durations (10 months) from time of initial radiotherapy between control and interferon patients.

Aged↗
PubMed1992

Serum osteocalcin in the management of myeloma.

We have measured serum osteocalcin, a vitamin K-dependent glycoprotein synthesised by osteoblasts in 62 patients, 49 with myeloma, 26 at presentation and 23 previously treated, 7 with Waldenstrom's macroglobulinaemia (WM), and 6 with monoclonal gammopathy of uncertain significance (MGUS). Osteocalcin levels were normal in WM and MGUS. High values were found in 5/26 (19%) patients with myeloma at presentation. There was no relationship between serum osteocalcin and stage of disease. Osteocalcin was normal in all patients in plateau phase, falling to low levels in relapsed patients who failed to respond to further treatment. Serum osteocalcin may be a useful indicator of bone metabolism in myeloma.

Adult↗
PubMed1992

Aztreonam plus vancomycin versus gentamicin plus piperacillin as empirical therapy for the treatment of fever in neutropenic patients: a randomised controlled study.

The efficacy of aztreonam in combination with vancomycin was compared with that of gentamicin plus piperacillin as empirical antibiotic treatment for fever in 61 neutropenic patients. Aztreonam plus vancomycin was as effective, but no more effective, than gentamicin plus piperacillin. Aztreonam showed excellent clinical and in vitro efficacy against Gram-negative pathogens. Failure to respond to aztreonam plus vancomycin was, in most cases, due to presumed or documented fungal infection; by contrast, failure to respond to gentamicin plus piperacillin was frequently to be due to resistant or superadded infection with Gram-positive bacteria.

Adult↗
PubMed1992

Piperacillin/tazobactam plus gentamicin as empirical therapy for febrile neutropenic patients with haematological malignancy.

The efficacy of piperacillin/tazobactam (PIPC/TBT) in combination with gentamicin was assessed as empirical therapy in 44 febrile neutropenic patients with haematological malignancy. A favourable response to therapy was seen in 67% patients overall and in 57% of patients with microbiologically documented infection. PIPC/TBT demonstrated good clinical and in vitro activity against isolated pathogens, particularly Gram positive cocci such as Staphylococcus epidermidis. The MIC of both Gram positive and Gram negative pathogens to PIPC was reduced in the presence of TBT. PIPC/TBT plus gentamicin is a safe and effective combination for empirical therapy in febrile neutropenic patients, even in a unit with a predominance of Gram positive infections.

Adolescent↗
PubMed1992

Evaluation of the in vitro antiproliferative properties of four novel anthracyclines YM1, 3, 4 and 6 in human leukemia cell lines.

The antitumor activity of novel doxorubicin analogues YM1, YM3, YM4 and YM6 was evaluated against drug sensitive U937 monocytic leukemia and CCRF-CEM lymphoid leukemia cell lines, as well as drug resistant CEM/VLB100 lymphoid multidrug resistant leukemia cell line by a [3H]thymidine incorporation assay. Different antileukemic activities of these new anthracyclines were observed in our studies. These novel anthracyclines produced a dose- and time-dependent inhibition in all the leukemic cell lines tested, while YM1 and YM3 were more effective than YM4 and YM6 against all the leukemic cell lines. The antitumor activity of all these novel analogues was lower than that of doxorubicin or epidoxorubicin in drug sensitive leukemic cells. The relative resistance values (IC50 of resistant cell line/IC50 of sensitive parental cell line) of YM1, 3, 4 and 6 were 27, 7, 5 and 14 respectively. These were lower than the resistance values for ADM and EDR which were 45 and 40 respectively. YM3 had a similar antileukemic activity against the CEM/VLB100 drug resistant leukemic cell line to ADM or EDR with a lower relative resistance value and a slightly increased IC50 value. Our results suggest that YM3 may be used in high dose for the clinical treatment of leukemias with possible less cardiotoxicity as well as less drug resistance.

Antineoplastic Agents↗
PubMed1992

A comparative study of imipenem versus piperacillin plus gentamicin in the initial management of febrile neutropenic patients with haematological malignancies.

Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.

Adolescent↗
PubMed1992

The histocompatibility antigen in asbestos related disease.

Thirty nine phenotypes of human leucocyte antigens (HLA)-A-B-DR and DQ were obtained from 99 asbestos workers (one woman and 98 men). Presence or absence of antinuclear antibodies and rheumatoid factor was determined in 91 of them. Workers were divided into five groups: asbestos workers with no apparent disease (AW; n = 17), diffuse benign pleural disease (PD; n = 31), asbestosis (AS; n = 24), asbestosis with lung cancer (AS-CA; n = 14), and mesothelioma (M; n = 13). Compared with AW, several trends of differences of HLA antigen prevalence were found in patients with asbestos related disease, but these did not achieve statistical significance when p was corrected (pcorr) by number of analyses undertaken. Analysis of the results obtained in previous studies together with the results of this study showed that compared with AW, AS patients had decreased prevalence of HLA-DR5 (pcorr < 0.02). Reasons for the differences in results of previous studies and statistical methods commonly used to compare prevalences of HLA antigen are discussed.

Adult↗
PubMed1992

Recombinant alpha 2B interferon in combination with oral chemotherapy in late chronic phase chronic myeloid leukaemia.

The place of alpha interferon (IFN) therapy in the treatment of chronic myeloid leukaemia (CML) is under intensive investigation at present. It is now established that as a single agent it can provide good disease control in the chronic phase and that cytogenetic responses will occur in a minority of patients. However its impact on long term survival has been less certain. Optimal haematological and cytogenetic results have to date been seen when IFN is used in the early phase of the disease, i.e. within one year of diagnosis. We have performed a prospective single arm study on the effect on survival of the addition of low dose IFN (9 mU/week) to conventional oral chemotherapy in patients who were at a median of 19 months from the initial diagnosis at the time of study entry. Comparison of this cohort with a control group of CML patients treated with oral chemotherapy only at the same participating institutions gave an estimated 72% reduction in the risk of death as a result of IFN therapy. Median survival for the IFN group has not been reached at 43 months compared with a median survival of 33 months for the chemotherapy alone group. These results suggest that the introduction of low dose IFN at any stage in the chronic phase may produce a worthwhile improvement in survival.

Antineoplastic Agents↗