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Biomedical subjects

A C Parker

Publications and source records attributed to A C Parker.

At least 19 recordsLinked to original sources

Peripheral blood stem cell transplantation.

Haematopoietic stem cells are usually sessile within the bone marrow microenvironment. However, small numbers do circulate in the peripheral blood of normal individuals, and following chemotherapy and/or intravenous growth factors, a substantial transient rise in circulating stem cells occurs. Leukocytes harvested by cytapheresis at this time can be used for autologous reconstitution of the haematopoietic and lymphoid systems following high dosage chemo/radiotherapy for the treatment of malignant disease. Peripheral blood stem cell transplants give rise to similar disease response rates as autologous bone marrow transplants, but have the advantage of more rapid haematopoietic reconstitution, and in addition can be offered to patients in whom marrow harvest is not feasible due to bone marrow damage or infiltration. This article reviews the theoretical and historical background to haematopoietic stem cell research, current clinical practice in peripheral blood stem cell mobilisation and harvesting, addresses the potential advantages and disadvantages compared to bone marrow transplantation, and assesses current experience of comparative efficacy.

Animals

An HIV positive haemophiliac with acute lymphoblastic leukaemia successfully treated with intensive chemotherapy and syngeneic bone marrow transplantation.

A 26-year-old HIV positive severe haemophiliac developed Burkitt-type acute lymphoblastic leukaemia with intracranial involvement. He underwent standard combination therapy, and entered complete remission. Syngeneic bone marrow transplantation (BMT) was undertaken; the donor was also HIV positive. The patient died 18 months from transplant of isolated intracranial relapse, with no evidence of systemic relapse. Unlike other types of non-Hodgkin's lymphoma, Burkitt's type occurs in HIV positive patients with relatively normal CD4 cell counts. Remission can be achieved using intensive chemotherapy, and since these patients may otherwise have a reasonable life expectancy, BMT may be appropriate.

Adult

Circulating progenitor cells in myelofibrosis: the effect of recombinant alpha 2b interferon in vivo and in vitro.

We have studied circulating progenitor cells in patients with myelofibrosis, the effects of recombinant alpha 2b interferon (IFN) treatment on these cells in vivo and in vitro and the patients' clinical response to IFN treatment. A 75-fold increase in circulating granulocyte macrophage colony forming units (CFU-GM) and a 25-fold increase in multilineage colonies (CFU-GEMM) were seen in the patients compared with controls. Patients who had undergone splenectomy had circulating progenitors within the normal range. IFN treatment of two patients resulted in clinical improvement and reduction in spleen size, but was complicated by a fall in platelet count and persistent malaise. Whilst on treatment the circulating progenitor cells increased up to 5-fold. In contrast, the addition of IFN in vitro to the CFU-GM and CFU-GEMM culture plates resulted in a dose-dependent inhibition of colony growth which was unaffected by the removal of T-cells and monocytes. Thus we confirm that circulating progenitors are raised in patients with myelofibrosis, IFN may be of benefit clinically, reducing spleen size but may increase levels of these cells in vivo. This is in contrast to the inhibitory effect of IFN in vitro on CFU-GM and CFU-GEMM growth.

Colony-Forming Units Assay

Human erythrocyte fraction in "Percoll" density gradients.

A new rapid method for the age fractionation of human erythrocytes by centrifugation through a "Percoll" density gradient is described. The fractionation is demonstrated by density-related changes in the volume, haemoglobin concentration, pyruvate kinase and acetylcholine esterase activities and potassium contents of the erythrocytes, and the distribution of reticulocytes on the gradients.

Acetylcholinesterase

Sea blue histiocytosis in a patient with chronic non-neuropathic Niemann-Pick disease.

A patient with Niemann-Pick disease is reported together with family studies. Her liver and bone marrow were shown to be infiltrated with sea blue histiocytes. Other organs, spleen and lung, were presumably also involved but histological proof was not obtained. Enzyme assay of leucocytes, lymphocytes, and cultured skin fibroblasts showed the patient to be deficient in sphingomyelinase activity. In fibroblasts, activity was 5% of normal while for the parents activity was about 50% of normal. The expected partial deficiency was not found using leucocytes or lymphocytes from the parents. Heat stability studies on fresh fibroblast extracts from the propositus indicated that residual sphingomyelinase activity was slightly more labile than that of the controls. It seems clear that chronic Niemann-Pick disease without neurological involvement is associated with sea blue histiocytosis.

Bone Marrow

Ultrastructural studies of leucocytes which form rosettes with homologous erythrocytes in human auto immune haemolytic anaemia.

Leucocytes which form rosettes with himologous erythrocytes in auto-immune haemolytic anaemia, infectious mononucleosis and following the stimulation of lymphocyte cultures with PHA have been studied by electron microscopy. The studies showed that the predominant homologous rosette forming cell was lymphocytic and the evidence favoured the conclusion that they were non-immune in nature. This identification does not classify the lymphocyte as thymus or bone marrow derived. Just under half (44%) of the total lymphocytic RFC had perinuclear microfilaments and limited clearing of the plasma of ribosomes close to the cell membrane. These features are consistent with activated T lymphocytes. The remainder of the lymphocytic RFC had no features which allowed their identification as T or B cells. The form of contact between lymphocytic RFC and erythrocyte was mainly of a pointlike nature, with little deformation or invasion of the attached erythrocytes. Monocytes were the only other type of cell encountered with any frequency. Their prime distinguishing feature was the deformation of attached red cells which they caused.

Anemia, Hemolytic, Autoimmune

Surface membrane characteristics of cells from human acute monocytic leukaemia.

The clinical and laboratory features of 4 patients with acute monocytic leukaemia are described. Surface membrane receptor studies of these patients have shown increasing strength of receptor expression occurs with increasing morphological maturity of the monocyte. In addition, the study shows that expression of membrane receptors can vary from patient to patient and also with time and treatment in an individual patient. A further finding has been the loss of positivity with specific anti-monocyte serum when the disease becomes refractory to therapy.

Adult

Activated T-cell in autoimmune haemolytic anaemia.

In 12 of 14 patients with clinically active autoimmune haemolytic anaemia high levels (9-78%) of homologous and autologous rosetting cells were found in the peripheral blood. In 10 of these patients, who were observed over a period of 2 years, the levels bore a direct relationship to the activity of the disease. The cells so identified were T-lymphocytes. The role of cells, identified by this method in AIHA, is discussed.

Adolescent

Recovery of hypothalamic-pituitary-adrenal function after intermittent high-dose prednisolone and cytotoxic chemotherapy.

Hypothalamic/pituitary and adrenal (HPA) function was assessed in ten patients who received intermittent high-dose prednisolone and cytotoxic chemotherapy for 5-40 months. Standard insulin hypoglycaemia (IHT), thyrotrophin-releasing hormone and tetracosactrin tests were performed 36 hr after the last dose of prednisolone and subsequently 10 days--52 weeks after completion of all chemotherapy. In the first tests there was evidence of impaired hypothalamic-pituitary function judged by peak adrenocorticotrophic hormone (ACTH), growth hormone (GH) and thyrotrophin (TSH) responses, and corresponding plasma corticosteroid responses were sub-normal in five patients. In the final IHTs, seven patients had persistently subnormal ACTH responses but all the corresponding plasma corticosteroid responses returned to normal. Mean peak corticosteroid responses to insulin and tetracosactrin and peak GH responses were significantly greater than in the first tests. Such chemotherapy regimens may have prolonged effects on hypothalamic/pituitary function but the demonstration of normal corticosteroid responses to hypoglycaemia and tetracosactrin indicates that these patients' stress responses will be normal as early as 10 days after treatment is stopped.

Adrenal Cortex Hormones

Oral or parenteral iron therapy in haemodialysis patients?

In 28 haemodialysis patients, in whom there was a high incidence of depleted marrow iron stores, a significant rise in Hb, and Hct, occasionally to a normal level, was achieved as effectively with oral as with i.v. iron supplements. There was a variable response to iron in individuals which could not be predicted from the initial iron status. No patient in whom marrow iron stores were reassessed after iron therapy developed increased marrow iron stores. Routine iron supplements are recommended in haemodialysis patients with regular monitoring of body iron stores.

Administration, Oral