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Biomedical subjects

J A Child

Publications and source records attributed to J A Child.

At least 91 records · Page 5Linked to original sources
PubMed1983

Defective neutrophil function and microbicidal mechanisms in the myelodysplastic disorders.

Neutrophil function studies have been carried out in a series of 44 patients with primary myelodysplastic syndromes (MDS). In vitro tests of phagocytosis and killing of Candida guilliermondii and Staphylococcus aureus identified 13 patients with abnormal neutrophil function at presentation and a further 10 who developed abnormalities during the course of their disease. The incidence of defective function in the five disease categories in this series was: refractory cytopenia (RC) 8/17; refractory cytopenia with sideroblastic change (RC + SC) 5/8; acquired idiopathic sideroblastic anaemia (AISA) 2/4; refractory anaemia with excess blasts (RAEB) 7/11; chronic myelomonocytic leukaemia (CMML) 1/4. Eleven of 23 patients with defective neutrophil function experienced severe infective complications; in only three of these patients were neutrophil counts less than 1 X 10(9)/l and susceptibility to infection was considered to reflect, at least partially, qualitative neutrophil abnormalities. There was no correlation between absolute neutrophil count and defective function. Abnormal overall neutrophil microbicidal activity was equally associated with impaired and normal phagocytosis. Some patients with intracellular killing defects had reduced myeloperoxidase (MPO) activities and one had reduced hexose monophosphate shunt (HMPS) activity. In two patients, whose neutrophils showed markedly impaired candidacidal activity, levamisole corrected function when added in vitro at 10(-7) M and also when administered in therapeutic dosage. It is suggested that deranged function, probably reflecting abnormalities in maturation of the granulocyte series, occurs across the myelodysplastic spectrum and that several microbicidal mechanisms may be defective.

Adult↗
PubMed1983

Comparison of the effects of filtration leucapheresis and discontinuous flow centrifugation leucapheresis on granulocyte microbicidal function.

In an investigation of the in vitro phagocytic and microbicidal function of granulocytes collected by filtration leucapheresis (FL) from 18 donors and by discontinuous flow centrifugation leucapheresis (DFC) from six donors, comparison was made with the function of granulocytes obtained from the same donors by venepuncture and density gradient centrifugation over Ficoll-Isopaque (FI). No significant impairment of the phagocytosis or killing of Candida guilliermondii by either FL- or DFC-granulocytes was observed. Although the ability of FL-granulocytes to phagocytose and kill Staphylococcus aureus did not differ significantly from the function of control FI-granulocytes, DFC-granulocytes were significantly less active.

Adult↗
PubMed1983

Serum beta-2-microglobulin in disorders of myeloid proliferation.

Serum beta-2-microglobulin (beta 2-m) was measured on 182 samples from 98 patients with diseases characterized by proliferation of predominantly non-lymphoid marrow elements. Raised levels were found in myeloproliferative disorders, chronic granulocytic leukaemia, acute myeloid leukaemia and in many patients with myelodysplastic syndromes. The most striking elevation was seen in acute and chronic myelomonocytic leukaemia. These raised serum levels are probably derived from increased cell turnover, and it is suggested that cells of monocyte-macrophage series are particularly high producers of beta 2-m.

Anemia, Aplastic↗
PubMed1982

An EORTC phase II study of methyl-glyoxal bis-guanylhydrazone in advanced renal cell cancer.

In a phase II study of methyl-glyoxal bis-guanylhydrazone (methyl-GAG) in patients with bi-dimensionally measurable metastases of renal cell cancer, 30 patients were given 500 mg/m2 weekly for at least 4 treatment cycles and were evaluable for response. Three patients (10%) achieved partial remission (PR) with a duration of 8-12 weeks; in 11 patients the disease was assessed as stable; and in 16 there was progression. A total of 40 patients were evaluable for toxicity. Nausea and vomiting occurred in 17 (43%), neuropathy, myopathy or myalgia in 8 (21%) and mucositis in 6 (14%). In addition to 3 patients taken off treatment before 4 treatment cycles, toxicity precluded further treatment in 3 others after 5, 6 and 7 cycles respectively. Methyl-GAG has minimal activity in renal cell cancer and, in this dose schedule, causes appreciable toxicity.

Adenocarcinoma↗
PubMed1982

An investigation of factors influencing serum NCA (non-specific cross-reacting antigen) level in patients with chronic myeloid leukaemia.

The NCA (nonspecific cross-reacting antigen) was assayed in sera of patients with chronic myeloid leukaemia (CML). It was elevated to a mean value of 145·6 ng/ml (± 104·4 ng/ml) compared to 37·8 ng/ml (± 14·6 ng/ml) the sera of normal subjects. Patients with active disease generally had higher serum NCA levels than those with CML in blast crisis. A correlation of the serum NCA levels with the cellular contents of this antigen was attempted using different methods. Large variations of serum NCA levels were observed in different patients having roughly similar white blood cell (WBC) counts. In general a better correlation was observed between the serum NCA level and the number of maturing myeloid cells than with the number of polymorphs. The staining of blood smears with anti-NCA serum by an immunoperoxidase method suggested an explanation for some cases of CML in blast crisis with normal serum NCA levels inasmuch as the staining of myeloid cells was very weak or negative in these cases, indicative of a lack of NCA synthesis in the cells. In other cases, cellular NCA was measured by radioimmunoassay in maturing myeloid cells and polymorphs. The mean values were not significantly different from the NCA values obtained in normal polymorphs. From the NCA content/10(6) cells and the polymorph or maturing myeloid cell counts, we calculated the total NCA cell content/ml of blood. It was much higher than, though poorly correlated with, the serum NCA level. Thus factors other than NCA cellular content, mainly the rate of NCA release from the myeloid cells, might play an important role in the regulation of its serum level.

Antigens↗
PubMed1982

Glucocorticoid binding and cytolethal responsiveness of hairy-cell and chronic lymphocytic leukaemia.

The glucocorticoid binding properties and cytolethal responsiveness of leukaemic cells were studied in vitro in seven patients with hairy-cell leukaemia (HCL) and five with chronic lymphocytic leukaemia (CLL). Substantial levels of glucocorticoid binding were detected both in whole cell and cytosol preparations from all patients although the level of binding by HCL cells always exceeded that of CLL cells (P less than 0.05). In both leukaemic cell types the uptake and binding of prednisolone in vitro was significantly greater than that of dexamethasone (P less than 0.05). CLL cells showed a variable dose-related cytolethal response to methylprednisolone sodium succinate (MPSS) treatment in vitro although cytolytic effects were not marked in the usual pharmacological dose range (10(-5)-10(-6)M). Treatment of CLL patients with conventional doses of prednisone for extended periods or high intravenous infusions of MPSS over shorter periods had no consistent effect on the in-vitro level of steroid binding or the cytolethal responsiveness of CLL cells to glucocorticoid treatment. Although HCL cells proved highly resistant to the cytolethal effects of MPSS in vitro, the substantial binding of glucocorticoids by leukaemic cells from all HCL patients indicates the potential value of steroid therapy in this disease should be explored further.

Administration, Oral↗
PubMed1981

Relative importance of renal failure and increased bone resorption in the hypercalcaemia of myelomatosis.

In order to define the relative importance of renal failure and increased bone resorption in the hypercalcaemia of myelomatosis 22 untreated patients were studied, of whom 12 were hypercalcaemic. Most patients had malabsorption of radiocalcium from the gastrointestinal tract and evidence of increased bone resorption as assessed by fasting urinary hydroxyproline/creatinine ratio. The mean OHPr/Cr ratio, however, was similar in patients with and without hypercalcaemia. Renal failure and Bence Jones proteinuria occurred more frequently in the hypercalcaemic patients. In four patients with hypercalcaemia there was an increase in OHPr/Cr after saline infusion accompanied by an improvement in renal function and hypercalcaemia. Mithramycin given to the same patients further reduced hypercalcaemia, presumably by inhibiting bone resorption. It was concluded that the hypercalcaemia of myelomatosis is due to the combination of renal failure and increased bone resorption, but that the OHPr/Cr ratio in the untreated state is a poor indicator of the degree of bone resorption in hypercalcaemic patients.

Acute Kidney Injury↗
PubMed1980

Serum beta 2-microglobulin in myelomatosis: potential value in stratification and monitoring.

In a longitudinal study of the evolution of serum beta 2-microglobulin (beta 2-m) levels in 37 patients with myelomatosis, those patients with a level of < 4 mg/l at first presentation had a median survival of 46 months, whereas those with an initial level of > mg/l had a median survival of 15 months. THe beta 2-m appeared to be independent of the level of the paraprotein and its class, as seen in a vertical study of 129 patients. Analysis of the influence of a rising serum creatinine on the serum beta 2-m indicates that beta 2-m production is excessive in advanced disease with or without renal failure. Practical application of the measurement of serum beta 2-m in the stratification and monitoring of patients is suggested.

Beta-Globulins↗
PubMed1980

The histopathology of prolymphocytic leukaemia with particular reference to the spleen: a comparison with chronic lymphocytic leukaemia.

The histological features of prolymphocytic leukaemia are described in spleen, lymph nodes, liver and bone marrow from nine cases. Eight patients had B-PLL one had T-PLL. These features were compared with those of six cases of B chronic lymphocytic leukaemia (B-CLL) with massive splenomegaly. Both PLL and B-CLL showed enlargement of the white pulp with nodule formation and diffuse infiltration of the red pulp. In both PLL and CLL larger cells were found in the white pulp nodules often concentrated on the periphery producing a bizonal appearance. The extent of involvement of the white pulp was greater in PLL than in uncomplicated CLL. However, this was not so in two cases of B-CLL in prolymphocytoid transformation in which the heavy replacement of the white pulp by large cells without a bizonal arrangement had effaced the red pulp. The cytological differences between PLL and CLL were best appreciated in splenic red pulp. The cells of CLL were small lymphocytes with clumped chromatin, those of PLL were larger with bigger nuclei, often indented in some cases, and distinct nucleoli. The pattern of infiltration in the bone marrow, liver and lymph nodes was similar in PLL and CLL. In conclusion, PLL can be distinguished from CLL by morphological and immunological features. The distinction is important clinically, because the survival of PLL is shorter than that of CLL.

Aged↗
PubMed1980

A new neutrophil candida killing test: chromium-51 release from Candida guilliermondii.

Neutrophil candidacidal function was measured by a chromium-51 (51Cr) release technique, using Candida guilliermondii as the test organism. The effect of varying the neutrophil:candida ratio, the time course of 51Cr release, the effect of different serum concentrations, and the reproducibility of the technique were investigated. Results from 33 experiments, using neutrophils from 35 normal donors and six patients with known neutrophil defects, show the technique to be a reliable and reproducible assay of candida killing. The chromium release assay has the advantage of being easy to perform and not liable to subjective errors.

Candida↗
PubMed1980

Behaviour of serum beta 2-microglobulin and acute phase reactant proteins in chronic lymphocytic leukaemia. A multicentre study.

Changes in serum-beta 2-microglobulin (beta 2-m) levels were measured in 52 patients with chronic lymphocytic leukaemia during periods of observation of 5-43 months. While the majority of patients had elevated levels (> 3 mg/l), higher values tended to be associated with more advanced disease as assessed clinically. Patients with nonprogressive, predominantly Rai stage 0 and I disease had persistently normal or near normal beta 2-m levels, whereas patients with progressive, predominantly Rai stage II-IV disease, had higher levels often showing rapid changes. Sequential measurements of serum beta 2-m show patterns of change that reflect and may anticipate the clinical progression of the disease.

Adult↗
PubMed1980

Renal tubular damage without glomerular damage after cytotoxic drugs and aminoglycosides.

Cytotoxic agents and aminoglycosides when given for a maximum of eleven days damaged the renal tubules as indicated by an increased urinary beta 2-microglobulin (beta 2-m), N-acetyl-beta-D-glucosaminidase (NAG) and total protein. Methotrexate (MTX) caused the greatest changes among the cytotoxic agents studied. Prophylactic doses of aminoglycosides in surgical patients also caused tubuloproteinuria. The tubular damage was greatest when aminoglycosides were given to treat septicaemia complicating haematological malignancies in patients who had previously had cytotoxic drugs. However, even in these patients there was no evidence of glomerular failure or increased glomerular permeability seven days after beginning chemotherapy.

Acetylglucosaminidase↗
PubMed1979

Abnormal red-cell metabolism of pyridoxine associated with beta-thalassaemia.

Red-cell conversion of pyridoxine to pyridoxal phosphate was studied in control subjects, and patients with heterozygous and homozygous beta-thalassaemia. In 7% of control subjects the rate of pyridoxine conversion was well below the range found in the other control subjects (5.0-8.6%, mean 6.5%/g Hb x 10(-2)) but in heterozygous beta-thalassaemia was below that range in 63% of the patients. The conversion rate was also slow or borderline in the majority of patients with severe transfusion-dependent homozygous beta-thalassaemia, in spite of the presence of some donor cells; but was normal, or fast as in other anaemias, in all but one patient with mild homozygous thalassaemia. There was a much higher incidence of a slow conversion rate in the parents of the severe homozygotes than in parents of the mild homozygotes, illustrating the familial pattern. This supports our view that the red-cell conversion rate of pyridoxine is an inherited characteristic, independent of thalassaemia. The cause of a reduced rate of pyridoxine conversion was investigated. The increase to a normal rate following riboflavin ingestion suggests a defect in the activity of the flavin mononucleotide (FMN)-dependent pyridoxine phosphate oxidase.

Adenosine Triphosphate↗
PubMed1979

Microbicidal function of the neutrophils in hairy-cell leukaemia.

The ability of neutrophils from patients with hairy-cell leukaemia to kill Candida guilliermondii and Staphylococcus aureus in vitro was investigated. Of 10 patients, 8 showed defective candida killing, 5 defective bacteria killing, in comparison with normal controls. Study of those patients who underwent splenectomy suggests that neutrophil function can be improved by splenectomy. The possible causes of defective function in this disease are discussed.

Candida↗
PubMed1979

Family studies of red-cell metabolism of pyridoxine in beta-thalassaemia.

Red-cell conversion of pyridoxine to pyridoxal phosphate was measured in 12 families with thalassaemia and 2 normal families. A strong familial pattern was demonstrated and the evidence suggested that the rate of red-cell conversion of pyridoxine is an independently inherited characteristic.

Erythrocytes↗