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Biomedical subjects

C Bunch

Publications and source records attributed to C Bunch.

At least 55 records · Page 3Linked to original sources
PubMed1983

Quinine disposition kinetics.

Intravenous quinine dihydrochloride (5 mg kg-1 over 5 min) was given to seven healthy male volunteers. There were minor subjective symptoms in all subjects but no significant changes in pulse or blood pressure. There was significant prolongation of the electrocardiographic QRS and rate corrected QT intervals which was greatest between 1 and 4 min after completion of the quinine infusion. Values then returned towards baseline. Plasma concentrations of quinine were measured spectrophotofluorimetrically after benzene extraction. Peak plasma concentrations (mean +/- 1 s.d.) after the infusion were 5.1 +/- 1.3 mg 1(-1). Pharmacokinetic analysis fitted a two compartment open model in each case; distribution half-time (t 1/2, lambda 1) was 1.89 +/- 0.54 min (mean +/- 1 s.d.), elimination half-time (t 1/2, z) 11.1 +/- 2.1 h, apparent volume of the central compartment (V1) 0.57 +/- 0.32 1 kg-1, total apparent volume of distribution 1.80 +/- 0.37 1 kg-1 and total clearance 1.92 +/- 0.45 ml min-1 kg-1.

Adolescent↗
PubMed1983

Fetal-to-adult hemopoietic cell transplantation: is hemoglobin synthesis gestational age-dependent?

The most direct available approach to determine the cellular control of the switch from fetal to adult hemoglobin is to examine the pattern of hemoglobin synthesis by fetal hemopoietic cells after their transplantation to an adult animal. Such an experiment is potentially capable of distinguishing between several proposed hypotheses, and a suitable experimental animal is available, the sheep. Despite a present inability to obtain sustained hemopoietic cell engraftment in sheep, results in the first few weeks after transplantation show distinct differences in the pattern of hemoglobin synthesis by the engrafted fetal cells in the adult environment. Fetal cells at 70-75 days gestation continue to synthesize only fetal hemoglobin, whereas cells from 100-day gestation fetuses appear to rapidly switch to adult hemoglobin production after transplantation. The combined results of transplant experiments carried out throughout this age range point to the gestational age of the cells as a major factor determining the pattern of hemoglobin synthesis. However, the time at which the cells switch in the adult precedes that at which the cells would normally switch in utero by about 2-3 weeks. This may reflect the nonphysiologic "stress" imposed on the fetal cells or result from some form of induction by the adult environment.

Animals↗
PubMed1982

Sheep lymphocyte antigens: a preliminary study.

Sera from 287 sheep were screened for cytotoxic antibodies against sheep lymphocytes. Forty four antisera were selected which provisionally define 13 lymphocyte antigens. The frequency of these antigens was studied in 305 sheep from 8 flocks of different breeds. Family studies confirm that inheritance of sheep lymphocyte antigens is controlled by the autosomal codominant genes of at least 2 linked loci.

Animals↗
PubMed1981

Hemoglobin H disease and mental retardation: a new syndrome or a remarkable coincidence?

Each of three families of northern European origin contains a mentally retarded son with hemoglobin H (Hb H) disease. One parent is a carrier of mild alpha-thalassemia and the other is normal, suggesting that this form of Hb H disease results from the interaction between an inherited defect of alpha-chain production and one member of the pair in chromosome 16 and a new mutation on the other. Restriction-enzyme analysis indicated that the new mutation was not the same in the other three patients, and demonstrated at least two hitherto undescribed lesions involving the alpha-globin gene cluster. Unless the association between the Hb H disease and mental retardation is fortuitous, the new mutations may also be related to the development changes in these children. Since the mutations only came to light because there was concurrent inheritance of an additional alpha-thalassemia determinant, this type of mutation of chromosome 16 may have been overlooked in other mentally retarded patients.

Adult↗
PubMed1981

Cytosine arabinoside deamination in human leukaemic myeloblasts and resistance to cytosine arabinoside therapy.

1. The conversion of cytosine arabinoside into its active metabolite cytosine arabinoside triphosphate, and catabolism by deamination to uracil arabinoside, was measured in intact marrow myeloblasts from patients with acute myeloid leukaemia. The ratio of uracil arabinoside/cytosine arabinoside triphosphate ranged from 0.32 to 19.11. 2. The effect of tetrahydrouridine, and inhibitor of cytosine arabinoside deamination, on cytosine arabinoside triphosphate production was studied. The greatest increase of cytosine arabinoside triphosphate production caused by addition of tetrahydrouridine was 27%. 3. The increase in cytosine arabinoside triphosphate production wad not related to the ratio of uracil arabinoside/cytosine arabinoside triphosphate or to the deaminase activity per 10(6) cells. It wa proportional to the percentage change of cytosine arabinoside in the incubation medium. 4. The sensitivity of DNA synthesis to inhibition by cytosine arabinoside was measured in myeloblasts from 11 patients. Addition of tetrahydrouridine did not increase the sensitivity of the marrow to cytosine arabinoside. 5. Cytosine arabinoside deamination is unlikely to be an important mechanism of resistance in myeloblasts in vivo, although it may produce apparent resistance in vitro.

Adult↗
PubMed1981

Haemoglobin synthesis by fetal erythroid cells in an adult environment.

Although the developmental switch from fetal to adult haemoglobin production has been well characterized in terms of protein synthesis, very little is known about its control at the cellular level. In order to determine whether the switch is controlled by environmental factors or programmed into the haemopoietic cell population, we have studied the effects of transplantation of fetal and adult haemopoietic cells into lethally irradiated lambs on haemoglobin synthesis by the transplanted cells. In two lambs which were irradiated but not transplanted, two lambs which were grafted with autologous marrow, and one lamb which was grafted from an allogenic twin, haemoglobin synthesis showed an adult pattern following transplantation, with gamma-chain synthesis never exceeding 7% of non-alpha chain production. Of 11 lambs transplanted with fetal haemopoietic cells, only two showed evidence of engraftment. During the 24-26 d that these animals survived, haemoglobin synthesis showed a predominantly fetal pattern, though there was a gradual increase in beta-chain production of donor origin. This increase occurred earlier than would be expected from the gestational age of the transplanted cells, but more slowly than might be expected if environmental factors were entirely responsible for expression of adult or fetal haemoglobin synthesis.

Aging↗
PubMed1979

Cellular origins of the fetal-haemoglobin-containing cells of normal adults.

The origin of the small population of adult red cells which contain Hb F (F-cells) has been studied in a clonal disorder of haemopoiesis, polycythaemia rubra vera (P.R.V.). In eleven patients who had not received cytotoxic therapy F-cells comprised less than 0.1% to 11.9% of the circulating red cells, compared with 0.34% to 4.6% in 21 haematologically normal controls. Two additional patients were glucose-6-phosphate-dehydrogenase heterozygotes in whom the clonal nature of the P.R.V. could be demonstrated directly; they had F-cell values of 2.1% and 8.3%. These observations indicate that F-cells arise from the same population of stem cells as other adult cells and not from a separate stem-cell pool.

Aged↗
PubMed1979

Relation of "lymphoid" phenotype and response to chemotherapy incorporating vincristine-prednisolone in the acute phase of Ph1 positive leukemia.

Forty-four patients with Ph positive leukemia (36 developing blast crisis after chronic phase and eight presenting in acute leukemia) were classified into subgroups on the basis of reactivity of blasts with an anti-serum made against non-T,non-B acute lymphoid leukemia (ALL+), levels of terminal transferase enzyme (TdT+) and morphology. Positivity with anti-ALL serum was the most sensitive and reliable marker, and TdT was an important aid. The presence of "lymphoid" blasts in blast crisis of CML was related to the response to chemotherapy incorporating Vincristine and Prednisolone (VP). Patients with ALL+ blasts frequently (14 of 15 cases) responded to therapy while 21 of 25 patients who had no ALL+ blasts failed to respond. The clinical course of the ALL+ patients was variable: eight patients remitted with return to the appearances of the chronic phase; four patients demonstrated elimination of the Ph1 positive clone with hypoplasia and this was followed by normal (Ph1 negative) marrow regeneration in two. Subsequent relapse was of either the ALL+ "lymphoid" or the ALL-myeloid type. A regimen incorporating VP should be the treatment of choice in "lymphoid" blast crisis of CML.

Antigens, Neoplasm↗
PubMed1979

Pharmacokinetics of cytosine arabinoside in patients with acute myeloid leukaemia.

1 The pharmacokinetics of cytosine arabinoside were studied after a single i.v. bolus of 2 mg/kg ara-C in patients with newly diagnosed untreated AML, using a bioassay and GC-MS method to measure the plasma concentrations. 2 Most patients showed a bi- or tri-phasic decline in plasma concentrations with time. Plasma clearance was 3.9 to 18.1 l/min as measured by the GC-MS method, and terminal half-lives varied from 7--107 min. 3 There was poor correlation of the GC-MS assay with the bioassay, probably because the latter was interfered with by the release of endogenous nucleosides from blasts after after ara-C. 4 Plasma concentrations were measured by GC-MS during continuous infusions in 14 patients. Plasma clearances were much lower than after a bolus, 0.39 to 5.25 l/min. 5 There was no correlation of response (remission or fall in peripheral blast count) with exposure to ara-C calculated from infusion dose, clearance and duration of infusion. 6 This study shows that ara-C pharmacokinetics varies markedly from patient to patient and that there is a wide range in the plasma concentrations associated with therapeutic response.

Adolescent↗
PubMed1979

Iron induced increase in red cell size in haemodialysis patients.

In a group of haemodialysis patients who were iron loaded secondary to parenteral iron administration a slight but significant increase in red cell size was noted when compared to a normal population. This macrocytosis was not related to serum B12 or folate levels, or to the reticulocyte count. On stopping iron therapy both mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) values declined significantly as did serum ferritin and iron levels. Bone marrow smears were of normal or increased cellularity. When iron therapy was discontinued there was a steady fall in serum ferritin levels without a drop in haemoglobin values suggesting that the excess iron was available for haemopoiesis. These findings suggest that the increase in red cell size in this group of patients may have been induced directly by iron overload.

Adolescent↗
PubMed1975

Haemoglobin Bart's in Saudi Arabia.

The haemoglobin (Hb) patterns of 345 Shiite Saudi Arab cord bloods were examined by alkaline starch-gel electrophoresis. A fast-moving component, identified by structural analysis as Hb Bart's, was found in 52% of cases, the highest incidence of this variant yet recorded. The levels of Hb Bart's ranged from 0.5 to 16% of the total haemoglobin. The relative rates of synthesis of the alpha, beta and gamma-chains, measured by [3H]leucine incorporation, were estimated in 12 newborn Arab infants. There was an excellent correlation between the amount of Hb Bart's and the alpha/non-alpha-globin-chain production ratio. Furthermore there was a significant correlation between the level of Hb Bart's and morphological abnormalities of the red cells and the mean cell haemoglobin (MCH). These findings indicate that elevated levels of Hb Bart's in this population are due to the presence of alpha thalassaemia. The absence of hydrops fetalis and the rarity of Hb-H disease despite the intense inbreeding in this population, points to an alpha-thalassaemia genotype that is, in terms of phenotypic expression, intermediate between the heterozygous state for alpha-thalassaemia I and Hb-H disease. A possible molecular basis for this genotype is suggested.

Electrophoresis, Starch Gel↗
PubMed1973

Coma associated with vincristine therapy.

Three cases of coma after vincristine therapy are described. One patient had hyponatraemia and other features of inappropriate secretion of antidiuretic hormone. The effects were temporary, and full recovery occurred in all three patients.

Adolescent↗