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G Dolan

Publications and source records attributed to G Dolan.

At least 55 records · Page 3Linked to original sources
PubMed1995

Effect of age upon the induction and maintenance of anticoagulation with warfarin.

We aimed to examine the effect of age upon the control of anticoagulation with warfarin in ordinary clinical practice, using a retrospective examination of routine anticoagulation clinic records from the University Hospital, Nottingham. Considerable over-anticoagulation (international normalisation ratio (INR) > 6.0) during induction occurred in 54 (11%) of 495 patients and was more likely in older patients (p < 0.05). Lesser degrees of over-anticoagulation during induction (INR > 4.0) were also more common in older patients, occurring in 58% of those aged 75 or above. Loading doses of warfarin were not reduced in older patients. INR in the maintenance phase rose with age (p < 0.001) despite lower maintenance doses of warfarin (p < 0.001). An INR > 6.0 in the maintenance phase was noted in 24 (3%) of 739 patients and again was more likely in older patients (p < 0.05). Patients using ambulance transport to the clinic were older than those who did not (p < 0.01) and those aged over 75 had shorter intervals between clinic visits (p < 0.01). We conclude that doctors using warfarin therapy do not take sufficient account of the increased sensitivity of older people to warfarin. Hospital anticoagulant policies need implementation and evaluation.

Age Factors↗
PubMed1994

Protein C, antithrombin III and plasminogen: effect of age, sex and blood group.

We conducted a cross-sectional study of antithrombin III (ATIII), protein C (PC) and plasminogen (Plg) concentrations in a population of healthy plasma donors in the Trent Region. The distribution of values for protein C was log normal whereas for ATIII and Plg the distributions were positively skewed and differed significantly from normal and log normal. Males had higher antithrombin III concentrations (mean 1.10 iu/ml, range 0.72-1.65) than females (mean 1.07 iu/ml, range 0.75-1.69) (P = 0.001) and levels increased with age in women. Younger women aged 25-34 had significantly lower plasma concentrations of ATIII compared to males of similar age. For protein C, concentrations were higher in males (mean 1.07 u/ml, range 0.37-2.11) than in females (mean 1.01 u/ml, range 0.59-1.61) (P < 0.001) and levels increased with age in both sexes P < 0.001). In women, a novel difference in protein C concentration between ABO blood groups was noted. There was no significant difference in plasminogen concentration between males and females, and in women plasminogen decreased with age (r = -0.205, P < 0.001). We conclude that these variations in ATIII and protein C with age and sex are important considerations in the determination of reference ranges for these proteins.

ABO Blood-Group System↗
PubMed1994

Comparison of capillary whole blood, venous whole blood, and plasma concentrations of mefloquine, halofantrine, and desbutyl-halofantrine measured by high-performance liquid chromatography.

Whole blood mefloquine, halofantrine, and desbutyl-halofantrine concentrations were measured by high-performance liquid chromatography in capillary blood, venous blood, and venous plasma samples from patients along the Thai/Burmese border with falciparum malaria who were treated with either mefloquine (25 mg/kg) or halofantrine (24 mg/kg or 72 mg/kg). The limits of detection for mefloquine, halofantrine, and desbutyl-halofantrine were 50, 15, and 10 ng/ml, respectively, with 200 microliters whole blood samples. There was a good linear correlation (r > 0.9) between capillary and venous blood and between whole blood and plasma for all three compounds. Mefloquine concentrations in venous and capillary blood were very similar (mean ratio 1.02, 95% confidence intervals [CI] 0.95-1.09, n = 60), but were 1.15 times higher (95% CI 1.03-1.29) in whole blood than in plasma (n = 22). The halofantrine and desbutyl-halofantrine concentrations were 1.27 (1.12-1.45, n = 23) and 1.34 (1.16-1.55, n = 24) times higher in venous compared to capillary blood, while halofantrine but not desbutyl-halofantrine concentrations were lower in whole blood than in plasma (mean ratios: halofantrine: 0.83 [0.72, 0.94], n = 39 and desbutyl-halofantrine: 1.05 [0.96-1.15], n = 41). Measurement of mefloquine, halofantrine, or desbutyl-halofantrine in capillary blood is an accurate and practical alternative to venous blood sampling, and is particularly useful for sampling with children, and under field conditions when technical facilities are limited.

Adolescent↗
PubMed1993

Halofantrine versus mefloquine in treatment of multidrug-resistant falciparum malaria.

The continuing spread of multidrug resistance in Plasmodium falciparum malaria makes the search for alternative treatments ever more urgent. We have investigated the relative efficacy of halofantrine and mefloquine in two paired randomised trials on the Thai-Burmese border, a multidrug-resistant area. In the first trial, 198 patients with acute uncomplicated falciparum malaria were randomly assigned either the standard halofantrine regimen (24 mg/kg) or mefloquine (25 mg/kg). The cumulative failure rates by day 28 were 35% with halofantrine and 10% with mefloquine (p = 0.0002). In the second study of 437 patients, a higher dose of halofantrine (8 mg/kg every 8 h for 3 days = 72 mg/kg) was both more effective and better tolerated than mefloquine 25 mg/kg; the failure rates were 3% and 8% (p = 0.03), respectively, or 1% vs 6% after adjustment for possible reinfections (p = 0.009). The rate of failure was higher after retreatment than after primary treatment in all study groups. Halofantrine 72 mg/kg was especially effective in the retreatment of these recrudescent infections; the failure rate was 44% with mefloquine and 15% with high-dose halofantrine (relative risk 3.0 [95% CI 1.2-7.3], p = 0.008). Thus, high-dose halofantrine is better tolerated and more effective than mefloquine for the treatment of uncomplicated falciparum malaria in this area. However, evidence of possible cardiotoxicity will need to be investigated fully before a role can be established for halofantrine in the treatment of multidrug-resistant malaria.

Acute Disease↗
PubMed1993

Interaction of hepatitis B and hepatitis C infection in haemophilia.

The management of haemophilia has been greatly complicated by the clinical sequelae of viral infection acquired through contaminated blood products. Many haemophiliacs have been infected by several viruses and the interaction between these viruses may be complex. In a cohort of 42 anti-HCV positive haemophiliacs, five were also found to be positive for HBsAg. All five were HCV reverse transcriptase/PCR negative compared to the 4/37 (11%) anti-HCV positive haemophiliacs who were HBsAg negative (P = 0.0001). We have identified a striking interaction between hepatitis C (HCV) and hepatitis B (HBV) in haemophiliacs co-infected by these agents, suggestive of the phenomenon of viral interference.

Cohort Studies↗
PubMed1993

Characterization of an acute micromegakaryocytic leukaemia: evidence for the pathogenesis of myelofibrosis.

The current hypothesis for the pathogenesis of myelofibrosis involves the intramedullary release of growth factors from defective or abnormal megakaryocytes. We describe a case of an acute micromegakaryocytic leukaemia, in a patient with chronic myelofibrosis, that provides additional evidence for this concept. The micromegakaryocytes, which reached 223 x 10(9)/l, were characterized morphologically by both light and electron microscopy, immunocytochemically and by platelet peroxidase activity. The cells were shown to have a mature cytoplasm, containing alpha granules and the associated proteins; vWF:Ag, fibrinogen, fibronectin and protein S. DNA analysis, by both a Seescan Solitaire Plus image analysis system and flow cytometry, revealed nuclear immaturity, with 92% of cells being diploid. Serum markers of connective tissue synthesis, namely carboxy terminal peptide of procollagen I (PICP), procollagen terminal peptide III (PIIIP) and laminin all increased significantly following transformation and were associated with an increase in platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta). These observations support the current hypothesis for bone marrow fibrosis formation and provide, for the first time, a link between in vivo growth factor release, bone marrow stromal turnover and megakaryocyte mass. In addition, the release of biologically active TGF-beta may explain both the increased fibronectin and angiogenesis characteristic of myelofibrotic bone marrow.

Female↗
PubMed1991

Congenital sideroblastic anaemia in two girls.

Transfusion dependent congenital sideroblastic anaemia occurred in infancy in two unrelated girls. One girl developed early organ failure which was not prevented by standard chelation treatment. The combination of modest iron burden and putative intrinsic mitochondrial dysfunction could have accounted for the clinical picture. The other girl remained well, receiving regular transfusion and standard chelation treatment. She had normal liver function and no other evidence of organ damage. The syndrome is unlikely to be due to extreme lyonisation in carriers of the usual X-linked condition. The contrasting clinical patterns seen in these two patients suggest that transfusion dependent congenital sideroblastic anaemia may comprise a heterogeneous group of disorders. It is suggested that such children be carefully monitored for evidence of increasing iron overload so that organ damage can be prevented.

Anemia, Sideroblastic↗
PubMed1991

Extrapulmonary lymphomatoid granulomatosis presenting as Pancoast's syndrome.

We report the case of a 55 year old man who presented as Pancoast's syndrome associated with a left sided Horner's syndrome, a mass in the left supraclavicular fossa and marked weakness with wasting of the left arm consistent with a left sided brachial plexus lesion. Biopsy revealed the typical features of lymphomatoid granulomatosis. Neurological involvement is a rare presenting manifestation of this uncommon disease. Lymphomatoid granulomatosis should be considered as a rare but potentially treatable cause of Pancoast's syndrome.

Brachial Plexus↗
PubMed1990

Value of monoclonal anti-myeloperoxidase (MPO7) for diagnosing acute leukaemia.

The expression of myeloperoxidase (MPO) was studied in 100 cases of acute leukaemia (83 with acute myeloid leukaemia (AML) and 17 acute lymphoblastic leukaemia (ALL) by both a conventional cytochemical method and the immunocytochemical antiperoxidase (APAAP) technique using the monoclonal antibody MPO7. In each case the staining was evaluated by light microscopical examination (percentage of positive cells). Of the 83 cases of AML, 78 (93.9%) were positive for MPO7 compared with 70 (84.3%) by cytochemistry. Antibodies against the myeloid markers CD13 and CD33 were positive in 71 (85.5%) and 70 (84.3%) cases, respectively. Importantly, all cases of ALL were negative for both MPO7 and cytochemical MPO staining even when they were positive for CD13 and CD33. These results indicate that the anti-myeloperoxidase antibody MPO7 is the most sensitive and specific reagent for the diagnosis of AML and should therefore be included in routine immunophenotyping panels.

Antibodies, Monoclonal↗
PubMed1990

Immunoblastic lymphoma presenting with syncope due to sinoatrial node disease.

A 68 year old man presented with syncope associated with episodes of sinus arrest. He responded to insertion of a demand pacemaker. During investigation he was noted to have generalized lymphadenopathy and biopsy revealed that he had an immunoblastic lymphoma. Before further assessment could be made, he developed rapid atrial fibrillation, resistant to several anti-arrhythmic agents and died several days after admission. At autopsy a nodular plaque of lymphoma was found to overly the sinoatrial node which was markedly fibrosed with evidence of lymphomatous infiltration of the surrounding microvasculature.

Aged↗
PubMed1989

Antithrombin Sheffield: amino acid substitution at the reactive site (Arg393 to His) causing thrombosis.

A Sheffield family with a predisposition towards thrombosis has been shown to have a functional abnormality of antithrombin. The abnormality was detected as reduced heparin cofactor activity, with normal antigenic levels of antithrombin. Crossed immunoelectrophoresis performed in the absence and presence of heparin was normal. The antithrombin was isolated by heparin Sepharose affinity chromatography. It had normal mobility on SDS polyacrylamide gel electrophoresis. However, the second order rate constant of inhibition of thrombin was about half that of normal, and this was compatible with a heterozygous abnormality involving the reactive site. The antithrombin was further purified by chromatography on thrombin-Sepharose (to remove the normal component), reduced, S-carboxymethylated and fragmented with cyanogen bromide. A pool containing the reactive site region was digested with trypsin and the molecular size of peptides generated determined by fast atom bombardment mass spectrometry. The two peptides adjacent to the Arg393-Ser394 bond of mass 2290 and 700 were almost absent from the mass spectrum, but an additional peptide of mass 2952 was present. Subdigestion with V8 protease reduced the mass of this peptide to 1748. These peptides generated by trypsin and V8 protease were almost identical to those obtained when another variant, antithrombin Glasgow, was treated in the same way (Erdjument et al, 1988). It is concluded that the molecular abnormality of antithrombin Sheffield is identical to that of antithrombin Glasgow, Arg393 to His.

Adult↗