Biomedical subjects

A P Haynes

Publications and source records attributed to A P Haynes.

6 recordsLinked to original sources

PubMed1992

Abnormal cytoplasmic pH regulation during activation in uremic neutrophils.

Neutrophils isolated from ESRF patients demonstrated abnormal cytoplasmic pH changes after FMLP stimulation; the initial cytoplasmic acidification was absent (P less than 0.001 compared to controls) and the degree of alkalinization enhanced (P less than 0.05 compared to controls). This effect was not due to the absence of any of the factors associated with acidification in normal PMN since superoxide production was enhanced (P less than 0.05 compared to controls) and intracellular calcium release was normal. Our observations are not explicable by alterations in the function of the Na:H antiport since the kinetics of antiport activation by cytoplasmic pH were not different in uremic and control cells. Other factors must therefore be important in generating the abnormal pH response to chemotactic factors in uremic PMN. Cells from CAPD patients had some degree of initial acidification (P less than 0.001 compared to controls and P less than 0.05 compared to ESRF) and enhanced alkalinization (P less than 0.05 compared to controls). Preincubation of normal PMN in four-hour dwell PDE reproduced the responses of uremic PMN with absent acidification, enhanced alkalinization and enhanced superoxide generation after FMLP stimulation (P less than 0.05 compared to controls). Changes in the control of cytoplasmic pH in stimulated PMN may influence PMN function, and our observations may be relevant to the susceptibility of uremic patients to infection.

Adult↗

PubMed1992

Recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for malignant lymphoma: a British National Lymphoma Investigation double-blind, placebo-controlled trial.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is active in enhancing the production of mature myeloid cells in vitro and several phase I/II clinical trials have suggested that its administration may accelerate neutrophil recovery after autologous bone marrow transplantation (ABMT). We have conducted a multicentre randomized double-blind placebo controlled trial in patients with poor prognosis malignant lymphoma receiving an identical high-dose combination chemotherapy regimen with ABMT. 61 patients were entered and 29 in each arm of the trial were evaluated. Treatment with GM-CSF did not affect the period of severe neutropenia (absolute neutrophil count (ANC) of < 0.1 x 10(9)/l) but accelerated recovery to an ANC of 0.5 x 10(9)/l (median 14 d v 20 d in controls, P = 0.001). There was no significant difference in platelet recovery between the groups (GM-CSF group platelet dependent for 25 d v control 19 d, P = NS). The number of positive blood cultures was similar in both groups (GM-CSF 14 v placebo 13) and there were no differences in days of fever > 37.5 degrees C (median 8 v 6) or days on parenteral antibiotics (11 v 10). Patients receiving GM-CSF had a median period of hospitalization following BMT of 24 d (control 25). No significant major toxicity attributable to GM-CSF administration was detected. We have confirmed in a randomized trial that GM-CSF accelerates neutrophil but not platelet recovery following ABMT. We were unable to demonstrate any accompanying changes in clinical outcome and believe that further trials are necessary to assess the clinical value of GM-CSF in BMT.

Adolescent↗

PubMed1991

Perspectives in multiple myeloma: survival, prognostic factors and disease complications in a single centre between 1975 and 1988.

One hundred and forty-one patients with multiple myeloma, diagnosed at the City Hospital, Nottingham between January 1975 and October 1986, were followed until death or for at least two years in a retrospective study. Overall median survival was 25 months, with no significant improvement occurring during the study period; increasing age, ESR and serum creatinine concentration at diagnosis were independent predictors of shortened survival. Renal impairment developed in 56 per cent of patients but only 7 per cent died of renal failure. At least one episode of infection occurred in 55 per cent of patients, most commonly in the first month. There was a significant rise in the overall incidence of infection and in the proportion caused by Gram-negative bacteria during the study period. Raised serum urea and low haemoglobin concentrations at diagnosis were independent risk factors for subsequent infection. Infection was associated with 2.75-fold increased risk of death, independent of other risk factors. Prevention of infection is an important aim for improvements in the survival of patients in multiple myeloma.

Adult↗

PubMed1990

A novel flow cytometric method for measuring protein digestion within the phagocytic vacuole of polymorphonuclear neutrophils.

When rhodamine is attached to albumin at a high molar ratio its fluorescence is quenched but fluorescence is released when the protein is digested and the dye released. Using this observation it is possible to measure protein digestion within the phagocytic vacuole of neutrophils. The assay is simple, rapid and measures digestion even in the presence of abnormal phagocytosis.

Animals↗

PubMed1990

Acquired abnormalities of polymorphonuclear neutrophil function.

Normal polymorphonuclear neutrophils (PMN) in the circulation are resting cells expressing small numbers of low affinity receptors. During inflammation they are upregulated to increase expression of high affinity receptors and discharge both primary and secondary granules. This is reflected by a pattern of changes which can be detected in PMN from the circulation of patients with infection, trauma or burns. Different patterns of abnormality occur in patients with systemic disease and increased risk of infection such as diabetes and renal failure. Functional defects also occur in PMN from patients with acquired blood disorders. It is likely that PMN contribute to tissue damage in inflammatory and vascular diseases so that drugs which modulate PMN function will be of future therapeutic benefit.

Diabetes Mellitus↗

PubMed1990

Neutrophil function tests.

The complexity of the neutrophil response to inflammation creates many difficulties for the study of neutrophil function in vitro. The environment in which a neutrophil is placed can have marked effects upon a variety of cellular functions. Quantitative tests of neutrophil function present problems not only with assay design but also in the isolation of cells from peripheral blood without disturbing their normal physiology. It is desirable to isolate neutrophils from other leukocytes because soluble factors released by other cells can influence neutrophil function, and other cells may interfere with functional assays; for example, monocytes will phagocytose opsonized particles and eosinophils contain a potent peroxidase. Attention to physical parameters such as temperature, pH or osmolarity, and rigorous exclusion of endotoxin, permits neutrophils to be isolated in a resting state. Subsequent function tests must be selected with an understanding of normal neutrophil physiology and applied with an awareness of any associated technical problems. The investigation of abnormal neutrophil responses may necessitate the screening of several tests of function; for example, defective neutrophil killing may be the result of abnormal chemotaxis, phagocytosis or degranulation. Which tests are appropriate will depend upon the questions to be answered and on the quantity of cells available for study.

Cell Adhesion↗