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Biomedical subjects

J K Wood

Publications and source records attributed to J K Wood.

At least 19 recordsLinked to original sources
PubMed1992

Dispiro-1,2,4,5-tetraoxanes: a new class of antimalarial peroxides.

Dispiro-1,2,4,5-tetraoxanes 2-4 were synthesized as potential peroxide antimalarial drugs. They had curative activity against Plasmodium berghei in vivo at single doses of 320 and 640 mg/kg which confirms earlier unpublished data. Moreover, artemisinin (1) and 4 had equivalent ED50's against P. berghei in vivo in the multiple-dose Thompson test; neither showed any evidence of acute toxicity at total doses of more than 12 g/kg. Dispiro-1,2,4,5-tetraoxane 4 had IC50's comparable to those of 1 against Plasmodium falciparum clones in vitro. These results confirm the potential of dispiro-1,2,4,5-tetraoxanes as a new class of inexpensive peroxide antimalarial drugs.

Animals↗
PubMed1992

Effects of age, sex and the oral contraceptive on the platelet membrane fibrinogen binding site (glycoprotein IIb/IIIa).

1. We have studied the effects of age, sex and the oral contraceptive pill on platelet fibrinogen 'receptor' density (Bmax) and affinity (Kd). 2. [125I]-fibrinogen binding to gel-filtered platelets was assessed after stimulation with adenosine 5-diphosphate (ADP) and thrombin in 60 normal subjects; 37 females and 23 males. 3. For both agonists there was no significant difference in Bmax or Kd between the sexes. A trend towards increasing affinity (reduced Kd) with age was noted in the female group following ADP stimulation. This was not considered to be physiologically relevant. In the group as a whole no significant relationship of Bmax and Kd with age was demonstrated. 4. A further group of eight women taking low dose oestrogen combined oral contraceptive pill were studied on days 7, 14, 21 and 28 of the treatment cycle and compared with eight women with regular ovulatory cycles. No significant variations in Bmax or Kd were detected within or between cycles in these two groups.

Adenosine Diphosphate↗
PubMed1991

125I-fibrinogen binding to platelets in myeloproliferative disease.

Recent reports have suggested a variation in the density and affinity of fibrinogen binding sites in platelets from patients with myeloproliferative disorders (MPD) which may reflect platelet functional abnormalities in these subjects. We have investigated the binding of 125I-fibrinogen (125I-Fb) to gel-filtered platelets from a large relatively homogeneous group of patients with MPD compared to normal age matched controls. Twenty-two of the patients investigated had polycythaemia vera and four essential thrombocythaemia. The maximal density and affinity (Kd) of 125I-Fb binding was assessed by saturation analysis in gel-filtered platelets (GFP) stimulated with either 10 microM ADP or 150 mU thrombin. In addition the functional significance of the binding sites was studied by evaluating the response of GFP from the two experimental groups by assessing the effects of increasing concentrations of added fibrinogen on the response to 10 microM ADP using standard light transmission aggregometry. In both groups the density of fibrinogen binding sites expressed in response to thrombin stimulation was significantly higher (approximately 2-3 fold) than that found in response to ADP. However, fewer binding sites were detected in the MPD group as compared with the control group in response to both ADP and thrombin. The Kd for 125I-Fb was similar for both agonists in normal controls and was significantly lower than that found in the MPD subjects. Although the 125I-Fb binding study results indicate a significant reduction in both the number and affinity of fibrinogen binding sites in patients with myeloproliferative disorders, the clinical and functional significance of these findings remain uncertain.

Blood Platelets↗
PubMed1991

The clinical relevance of plasma viscosity in Hodgkin's disease.

The erythrocyte sedimentation rate has previously been identified as an important prognostic factor in Hodgkin's disease. The plasma viscosity has replaced the ESR measurement in many laboratories, but doubts exist about its clinical relevance. In this study plasma viscosity at presentation/diagnosis was studied in 107 patients with Hodgkin's disease. A multivariate analysis of factors influencing prognosis and relapse-free survival identified plasma viscosity and number of disease sites as being highly significant. The risk of relapse increases initially with a rise in plasma viscosity, but after a value of about 2.0 mPa.s no further increase in risk is observed. When all of the prognostic factors are made available to the proportional hazards model, treatment modality and plasma viscosity are selected as the best set for predicting time to first relapse. This study demonstrates that measurement of plasma viscosity at presentation is an important prognostic factor in Hodgkin's disease, in terms of predicting outcome or risk of relapse.

Adult↗
PubMed1990

The M1 Kegworth aircraft disaster: experience in three hospital blood transfusion laboratories and the regional transfusion centre.

Eighty-eight survivors of an aircraft accident on the M1 motorway were taken to three major hospitals, two of which were teaching hospitals, in the immediate vicinity. We describe the effects of this on the three blood transfusion and haematology laboratories concerned and on the regional transfusion centre, describe how the work was processed, and list the lessons learnt.

Accidents, Aviation↗
PubMed1988

Large granular lymphocytosis associated with rheumatoid arthritis.

A 74 year old woman with rheumatoid arthritis, hepatosplenomegaly, neutropenia, and peripheral blood lymphocytosis is described. The lymphocytes had a large granular morphology and expressed a CD3+ CD8+ Leu7+ surface antigen phenotype. They did not have natural killer cell function. Southern analysis of the lymphocyte DNA using two restriction enzymes showed a rearranged pattern for the T cell receptor beta chain gene, indicating a monoclonal lymphoproliferation. Large granular lymphocytosis is a rare and heterogeneous phenomenon, which has become more clearly characterised through the application of molecular biology techniques. Most cases appear to be forms of T cell leukaemia with a chronic benign course. The association between rheumatoid arthritis and large granular lymphocytosis is emphasised.

Aged↗
PubMed1988

Glycosylated haemoglobin: an index of glucose control in pancreatic islet transplanted rats.

In this study we have measured glycosylated haemoglobin in the blood of 22 rats made diabetic with streptozotocin. This significantly increased from a normal level of 1.6 +/- 0.2% to reach a maximum, plateau level, of 6.6 +/- 0.3% at 45 days. At this time, 16 of these animals were given intra-portal transplants of purified isologous pancreatic islets. By varying the number of islets transplanted, animals were produced with normal blood glucose levels on random sampling, but with a spectrum of glucose control as measured by the glucose tolerance test. The glycosylated haemoglobin level was also measured at 30, 60 and 120 days post transplantation. This was significantly reduced (in some cases back to normal) and at 60 and 120 days there was a significant correlation (p less than 0.001) between glycosylated haemoglobin and the glucose clearance (K value). These results suggest that the measurement of glycosylated haemoglobin can be used as a simple and accurate index of glucose metabolism in islet transplanted rats.

Animals↗
PubMed1988

Elective splenectomy in haematological disorders.

We report on 106 elective splenectomies performed for haematological disorders between March 1979 and January 1986. The most common indications were immune thrombocytopenic purpura (30 patients) and Hodgkin's disease (19 patients). However, staging laparotomy is no longer performed routinely for patients with Hodgkin's disease and the reasons for this are discussed. Other indications for splenectomy included splenic pain (13 patients), autoimmune haemolytic anaemia (12 patients), hereditary spherocytosis (11 patients) and hypersplenism (9 patients). The overall morbidity and mortality was 48% and 5% respectively. The most common postoperative complication was thrombocytosis (defined as a platelet count greater than 800 X 10(9)/l) and occurred in 26 patients. This review confirms that splenectomy continues to have an important role in the management of certain haematological disorders.

Adolescent↗
PubMed1987

A computer system for a blood transfusion laboratory.

A modified Phoenix data processing system has been introduced into the haematology laboratories in the Leicestershire District Health Authority. In the three blood transfusion laboratories the computer system has been fully operational for a year and has been found to aid the management of data within the department as well as improving the quality of the service.

Blood Grouping and Crossmatching↗
PubMed1985

Differential labeling of platelet alpha 2 adrenoceptors by 3H dihydroergocryptine and 3H yohimbine in patients with myeloproliferative disorders.

Platelet alpha adrenoceptor status was examined using the radioligands 3H-yohimbine (3H-YOH) and 3H-dihydroergocryptine (3H-DHE) in 14 patients with myeloproliferative disorder (MPD) and 10 normal controls. Platelets from normal controls and MPD patients sensitive to adrenaline induced aggregation exhibited approximately 50% more binding sites identified by 3H-DHE than 3H-YOH, whereas MPD platelets insensitive to adrenaline showed selective loss of these 'extra' 3H-DHE sites. In functional studies after 30 minutes preincubation with the unlabelled antagonists, DHE was more potent than YOH at inhibiting adrenaline induced aggregation in normal platelets. In addition, the affinity constant for DHE was virtually identical in binding and functional experiments, whereas for YOH the affinity constant for binding was approximately 10 fold more potent than that for aggregation. These results suggest that the alpha adrenoceptor binding site on human platelets labelled by 3H-DHE may be of more functional relevance than that labelled by 3H-YOH alone.

Blood Platelets↗
PubMed1985

Alpha 2-adrenoceptor coupling to adenylate cyclase in adrenaline insensitive human platelets.

Coupling of the alpha 2-adrenoceptor to adenylate cyclase was assessed in platelets from 3 groups of subjects: normal controls and patients with myeloproliferative disorders whose platelets were either sensitive or specifically insensitive to the aggregatory effects of adrenaline. The ability of adrenaline to induce the formation of a complex between the alpha 2-adrenoceptor and the inhibitory guanine nucleotide binding protein was examined in all three groups by assessment of the effect of mono and divalent cations and Gpp(NH)p on the displacement of [3H]yohimbine binding to platelet membranes by adrenaline. Coupling to adenylate cyclase was also assessed in separate studies of the inhibition by adrenaline of PGE1 stimulated cyclic AMP accumulation in whole platelets. Both the formation of the ternary complex and the inhibition by adrenaline of cyclic AMP accumulation was not significantly different in platelets sensitive or insensitive to adrenaline. These results suggest that inhibition of cyclic AMP alone does not explain the mechanisms of adrenaline induced platelet aggregation.

Adenylyl Cyclases↗
PubMed1979

Acquired von Willebrand's syndrome and Ehlers-Danlos syndrome presenting with gastro-intestinal bleeding.

The clinical and laboratory findings in a patient with severe gastro-intestinal bleeding and the Ehlers-Danlos syndrome are described. Coagulation studies and a lack of history of previous haemorrhage were consistent with a diagnosis of acquired von Willebrand's syndrome. His response to treatment with blood transfusion, Factor VIII, cimetidine, tranexamic acid and cyclophosphamide is described. Family studies revealed other members with Ehlers-Danlos syndrome but normal coagulation.

Aged↗
PubMed1979

Beta thromboglobulin and glycosylated haemoglobin in diabetes mellitus.

No correlation has been demonstrated between the elevated levels of plasma beta-thromboglobulin and glycosylated haemoglobin found in a group of 97 diabetic patients. The abnormality in diabetic platelets which is reflected by beta-thromboglobulin levels may not therefore be a direct result of poor metabolic control. The highest levels of beta-thromboglobulin were found in those patients with a raised blood urea. Glycosylated haemoglobin levels correlated with prevailing blood glucose and with the type of therapy employed, and were highest in the insulin dependent diabetics, intermediate in those on tablets and lowest in those on diet alone.

Adolescent↗