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Biomedical subjects

C Bunch

Publications and source records attributed to C Bunch.

At least 37 records · Page 2Linked to original sources
PubMed1988

Immunoglobulin replacement in chronic lymphocytic leukaemia.

Infection is a frequent cause of morbidity and mortality in patients with chronic lymphocytic leukaemia (CLL) and low-grade B cell lymphomas. Several factors may contribute to an increased risk of infection in individual patients but, overall, impaired antibody production--commonly manifest as hypogammaglobulinaemia--appears to be a major factor. Early studies of immunoglobulin replacement using the intramuscular route showed equivocal results. More recently, highly purified preparations of IgG have become available for intravenous use making regular replacement therapy a realistic possibility for patients at risk. We have recently undertaken a multi-centre, randomized, double-blind, placebo-controlled study of regular intravenous immunoglobulin (IVIg) replacement in patients with CLL at risk of infection as defined by presence of hypogammaglobulinaemia, a significant infection history, or both. Eighty-four patients with CLL were randomized to receive IVIg (Gammagard Baxter Healthcare Corporation Hyland Division), 400 mg/kg body weight or an equivalent volume of normal saline every 3 weeks for a year. Patients receiving IVIg showed a 45% reduction in bacterial infection during the study period (p = 0.01). In patients completing a full year of study, a 61% reduction in bacterial infection was observed (p = 0.001). A significant reduction in bacterial infection was also seen in a blinded crossover study in which 12 patients from one centre who had completed a full year in the former study were subsequently given the alternative infusion for a further year. The incidence of serious bacterial infection was significantly less during the months in which patients received IVIg compared with placebo (p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Agammaglobulinemia↗
PubMed1987

Identification of a novel 17,000-dalton parathyroid hormone-like adenylate cyclase-stimulating protein from a tumor associated with humoral hypercalcemia of malignancy.

Humoral hypercalcemia of malignancy is a common paraneoplastic syndrome which is characterized by hypercalcemia resulting from secretion by tumors of a circulating bone-resorbing factor. Evidence suggests that in many instances this factor is an adenylate cyclase-stimulating protein which shares features with, but is distinct from, parathyroid hormone (PTH). The current report describes the purification to homogeneity from a humoral hypercalcemia of malignancy-associated tumor of a novel, basic, highly potent PTH-like adenylate cyclase-stimulating protein. This factor differs from previously described PTH-like factors with respect to size, amino acid composition, and specific activity.

Adenylyl Cyclases↗
PubMed1987

Pharmacokinetics of intravenous amodiaquine.

Amodiaquine hydrochloride (3 mg base kg-1) was given by constant rate intravenous injection over 10 min to seven healthy adult male volunteers, and by constant rate infusion (10 mg base kg-1) over 4 h to 10 adult patients admitted to hospital with falciparum malaria. After intravenous injection in volunteers there was considerable variation in plasma concentration profiles between subjects; peak plasma concentrations ranged between 65 and 1921 ng ml-1. A biexponential equation was fitted to the plasma concentration time data and the following estimated pharmacokinetic parameters (geometric mean; range) were derived; lambda 1 = 24.4 (7.6-95.0) h-1, lambda 2 = 0.33 (0.12-0.79) h-1, V1:1.1 (0.3-3.6) 1 kg-1, Vss: 17.4 (2.3-95.9) 1 kg-1 and systemic clearance 13.0 (4.7-56.6) 1 kg-1 h-1. After intravenous infusion there was also considerable variability between patients with post-infusion plasma concentrations ranging between 82 and 836 ng ml-1. The plasma concentration-time profiles were biphasic with the following estimated pharmacokinetic parameters (geometric mean; range) alpha = 1.87 (0.60-8.52) h-1, beta = 0.069 (0.021-0.265) h-1, V1: 4.6 (0.5-29.3) 1 kg-1, Vss: 38.3 (3.7-127.9) 1 kg-1 and systemic clearance CL (1.6-17.3) 1 kg-1 h-1. There was no measurable long terminal elimination phase, and the principal metabolite desethyl amodiaquine was not detected in the plasma samples. There was no serious toxicity in either group. During intravenous injection there was a significant fall in systolic blood pressure in four subjects (mean fall 16 mm Hg) but there was no significant change in heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Anti-granulocyte opsonic activity in sera from patients with systemic lupus erythematosus.

Neutropenia is common in patients with systemic lupus erythematosus (SLE) but mechanisms of cell depletion remain obscure. To investigate the possible autoimmune aetiology of neutropenia in SLE, sera from 31 patients with this disorder were tested for anti-granulocyte activity. Granulocyte-binding immunoglobulins were detected by indirect immunofluorescence, and the ability of patient sera to opsonize granulocytes was determined by measuring the chemiluminescent response of human monocytes to granulocytes sensitized by test sera. Sera from 22 of the 31 patients bound IgG to granulocyte cell membranes and/or to nuclei, but only membrane-binding antibodies opsonized the cells for recognition by monocytes. There was no correlation between neutrophil count and the level of granulocyte-binding IgG as measured by indirect immunofluorescence. In contrast, opsonic activity and neutrophil count were inversely correlated (r = 0.5; P less than 0.05). However, opsonic activity was present in sera from most non-neutropenic patients. In patients with SLE, impaired reticuloendothelial system function may allow sensitized granulocytes to remain in the circulation.

Cell Membrane↗
PubMed1986

Frequency of severe neutropenia associated with amodiaquine prophylaxis against malaria.

6 out of 7 patients with severe neutropenia associated with the use of amodiaquine for malaria prophylaxis amodiaquine (400 mg weekly) plus proguanil (200 mg daily); 1 of these patients had also taken cotrimoxazole and another had taken sulphaguanidine. The 7th patient had taken amodiaquine alone, but at a higher dose. A retrospective analysis suggests that the frequency of severe neutropenia complicating amodiaquine taken prophylactically may be as high as 1 in 2000.

Acute Disease↗
PubMed1986

Cardiovascular toxicity and distribution kinetics of intravenous chloroquine.

Chloroquine diphosphate (3 mg base kg-1) was given by constant rate intravenous injection over 10 min to 12 healthy adult male volunteers. Plasma concentrations of chloroquine and the principal metabolite desethylchloroquine, electrocardiograph intervals, and arterial blood pressure were measured at frequent intervals to determine the relationship between cardiovascular effects and plasma concentrations. Peak plasma concentrations ranged between 784 and 6649 (mean 2913) ng ml-1. The decline in plasma concentrations was multiexponential with an initial rapid distribution phase; mean (+/- s.d.) first order rate constant 0.65 +/- 0.14 min-1, and an estimated apparent volume of the central compartment of 0.18 +/- 0.15 l kg-1. There was no serious toxicity, but subjective side effects were reported in all patients and there was a significant fall in systolic blood pressure (110 +/- 9.5 to 101 +/- 12.5 mm Hg; P = 0.03) and rise in heart rate which paralleled the change in plasma chloroquine concentrations. Coincident with changes in blood pressure, there was a significant prolongation of the electrocardiograph QRS interval; 81 +/- 15 to 92 +/- 13 ms (P less than 0.01) but no change in the QTc interval. These findings suggest that the cardiovascular toxicity of parenteral chloroquine is related to transiently high plasma concentrations occurring early in the distribution phase. This results from incomplete distribution from a central compartment that is approximately one thousand times smaller than the eventual total apparent volume of distribution at steady state. Rate of administration is therefore a major determinant of toxicity.

Adolescent↗
PubMed1986

Anti-granulocyte opsonic activity and autoimmune neutropenia.

Sera from patients with unexplained neutropenia have been assayed for anti-granulocyte opsonic activity using a chemiluminescence technique which measures the metabolic response of human monocytes to antibody-coated granulocytes. This rapid and simple technique was more sensitive than indirect immunofluorescence in the detection of anti-granulocyte antibodies. Anti-granulocyte opsonic activity was detected in sera from 17 of 31 patients, suggesting that their neutropenia may have had an autoimmune basis. The opsonic activity of five of the 17 sera was increased when granulocytes were sensitized in the presence of fresh serum. Four of these sera bound IgM and C3b to granulocytes in the immunofluorescence test. Human IgG when added to the monocyte suspension medium inhibited monocyte response to IgG antibody-opsonized granulocytes. This inhibition was less when granulocytes were opsonized with sera containing IgM and complement granulocyte-binding activity. This observation may be relevant to the selection of neutropenic patients for therapeutic use of intravenous immunoglobulin.

Adolescent↗
PubMed1985

Hepatic sequestration in sickle cell anaemia.

Several episodes of acute hepatic enlargement associated with a dramatic fall in haemoglobin concentration were observed in two patients with sickle cell anaemia. No appreciable disturbances of liver function or signs of cardiac failure were evident. The most likely mechanism was sequestration of sickled erythrocytes in the liver. This complication, which may have a basis similar to that of splenic sequestration and the sickle lung syndrome, may be easily overlooked unless the size of the liver is regularly monitored in patients with sickle cell crisis.

Adolescent↗
PubMed1985

The cellular basis of haemoglobin switching: further studies of fetal-to-adult haemopoietic cell transplantation.

The switch from fetal to adult hemoglobin synthesis appears to be due to a change in gene expression within the same hemopoietic lineage. The timing of this change looks to be largely determined by the gestational age of the hemopoietic cells, consistent with their containing an intrinsic developmental clock. Precocious switching of fetal cells in an adult environment could reflect an interaction of this clock with external factors or may result from an acceleration of the clock under the extreme experimental conditions, possibly associated with an increased rate of stem cell division.

Animals↗
PubMed1984

Erythroid differentiation in CGL cells from a patient with blast crisis.

A 60-year-old patient with Ph1 + ve CGL presented with blast crisis. The leukaemic blast cells resembled erythroblasts and had 51 chromosomes with two Ph1. Cells obtained from peripheral blood, marrow and a pleural effusion were cultured under a variety of conditions. After 2-3 weeks in culture, the model 51-chromosome line persisted but many of the cells displayed erythroid morphology and differentiated to resemble mature normoblasts, strongly positive on o-tolidine +ve staining. Haemoglobin analysis by starch gel and globin synthesis studies demonstrated only fetal haemoglobin (HbF) synthesis in the cultured cells whilst the patient's reticulocytes synthesized very little HbF. Restriction enzyme mapping of DNA from the cultured cells showed that beta-globin genes were still present in these cells even though they were not expressed.

Bone Marrow↗
PubMed1984

Mastoid surgery in chronic granulomatous disease.

A patient is reported with a severe inherited phagocytic defect, chronic granulomatous disease, in whom otological complications occurred. Successful ear surgery in this condition is described.

Adult↗