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Biomedical subjects

D Bevan

Publications and source records attributed to D Bevan.

At least 19 recordsLinked to original sources
PubMed2000

Management of intracranial bleeding associated with anticoagulation: balancing the risk of further bleeding against thromboembolism from prosthetic heart valves.

Mechanical heart valves are associated with a risk of thromboembolism and anticoagulation is generally recommended. However, this is inevitably associated with a risk of intracranial bleeding. The case of a patient who sustained an intracranial bleed while taking warfarin for a prosthetic aortic valve and a further two intracranial bleeds while on heparin as an inpatient is discussed and the literature on the management of intracranial haemorrhage in patients on warfarin with prosthetic valves is reviewed.

Aged↗
PubMed1999

Experiences of hospital care and treatment seeking for pain from sickle cell disease: qualitative study.

OBJECTIVE: To investigate how sociocultural factors influence management of pain from sickle cell disease by comparing the experiences of those who usually manage their pain at home with those who are more frequently admitted to hospital for management of their pain. DESIGN: Qualitative analysis of semistructured individual interviews and focus group discussions. PARTICIPANTS: 57 participants with genotype SS or S/beta-thal (44 subjects) or SC (9) (4 were unknown). 40 participants took part in focus groups, six took part in both focus groups and interviews, and nine were interviewed only. Participants were allocated to focus groups according to number of hospital admissions for painful crisis management during the previous year, ethnic origin, and sex. RESULTS: The relation between patients with sickle cell disease and hospital services is one of several major non-clinical dimensions shaping experiences of pain management and behaviour for seeking health care. Experiences of hospital care show a range of interrelated themes, which are common to most participants across variables of sex, ethnicity, and hospital attended: mistrust of patients with sickle cell disease; stigmatisation; excessive control (including both over- and undertreatment of pain); and neglect. Individuals respond to the challenge of negotiating care with various strategies. Patients with sickle cell disease who are frequently admitted to hospital may try to develop long term relationships with their carers, may become passive or aggressive in their interactions with health professionals, or may regularly attend different hospitals. Those individuals who usually manage their pain at home express a strong sense of self responsibility for their management of pain and advocate self education, assertiveness, and resistance as strategies towards hospital services. CONCLUSIONS: The current organisation and delivery of management of pain for sickle cell crisis discourage self reliance and encourage hospital dependence. Models of care should recognise the chronic nature of sickle cell disorders and prioritise patients' involvement in their care.

Adult↗
PubMed1999

Factors affecting the pharmacokinetic characteristics of rapacuronium.

BACKGROUND: Rapacuronium is a new nondepolarizing muscle relaxant with rapid onset and offset. As part of a study to determine its neuromuscular effects, the authors sampled plasma sparsely to determine the influence of age, gender, and other covariates on its pharmacokinetic characteristics. METHODS: Of 181 patients receiving a single bolus dose of 0.5-2.5 mg/kg rapacuronium, 43 (aged 24-83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed using a population approach (mixed-effects modeling) to determine the influence of demographic characteristics and preoperative laboratory values on the pharmacokinetic parameters. RESULTS: Rapacuronium's weight-normalized plasma clearance was 7.03 x (1 - 0.0507 x (HgB - 13)) ml x kg(-1) x min(-1), where HgB is the patient's preoperative value for hemoglobin (g/100 ml); however, rapacuronium's blood clearance (11.4+/-1.4 ml x kg(-1) x min(-1), mean +/- SD) did not vary with hemoglobin. Rapacuronium's weight-normalized pharmacokinetic parameters were not influenced by age, gender, or other covariates examined. Plasma concentrations of ORG9488 were typically less than 14% those of rapacuronium during the initial 30 min after rapacuronium administration. CONCLUSIONS: In this patient population, neither age nor gender influence elimination of rapacuronium. This finding contrasts to an age-related decrease in plasma clearance observed in a study of 10 healthy volunteers and in a pooled analysis of the pharmacokinetic data from 206 adults in multiple clinical studies. Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade.

Adult↗
PubMed1999

Increased resistance to activated protein C and factor V Leiden in recurrent abortions. Review of other hypercoagulability factors.

OBJECTIVE: To evaluate hereditary and acquired hemostatic abnormalities associated with recurrent spontaneous early (first-trimester) abortions. METHOD: A group of 56 Greek women with two or more unexplained primary spontaneous abortions, and a reference group of 148 women without a history of recurrent abortions, were screened for hypercoagulability. A randomly selected population of first-trimester pregnant women was also chosen for factor V Leiden genetic screening. RESULTS: A total of 21% of the women with recurrent abortions, compared with 12% of the reference group, showed increased activated protein C resistance. Fourteen per cent had positive lupus anticoagulant, compared with 11.5% of the reference group. For the rest of the parameters, there was no difference between the two groups. Of 22 women studied for factor V Leiden, one was homozygous and one was heterozygous. Results were compared using Fisher's exact test and two-tailed Student's t tests. CONCLUSIONS: Increased activated protein C resistance appears to be an important factor in women with recurrent abortions. These data indicate the need for routine investigation of activated protein C resistance in women with recurrent abortions.

Abortion, Spontaneous↗
PubMed1998

Cardiopulmonary bypass with danaparoid sodium and ancrod in heparin-induced thrombocytopenia.

Heparin is the standard anticoagulant for patients undergoing cardiopulmonary bypass. There are some patients for whom heparin is unsuitable and ancrod (a defibrinogenating enzyme) has been used as an alternative. We present a patient with heparin-induced thrombocytopenia in whom treatment ancrod was ineffective. The addition of danaparoid sodium (a heparinoid) allowed safe cardiopulmonary bypass. We discuss the reasons for this and suggest that the combination of ancrod and danaparoid sodium is a logical one in such cases.

Ancrod↗
PubMed1998

Three novel PROC gene lesions causing protein C deficiency.

Missense mutations, three of them novel (Asn210-->Val, Asn248-->Ile, Ala355-->Val), were found in the protein C (PROC) genes of 7 patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX causing haemophilia B and the use of molecular modelling has provided explanations as to how these lesions might alter either the structure, function or secretion of the protein C molecules encoded.

DNA Mutational Analysis↗
PubMed1998

Splenic lymphoma with villous lymphocytes should be included in the differential diagnosis of massive splenomegaly.

AIM: To distinguish between patients with reactive lymphocytosis and those with malignant lymphoid proliferations, with particular reference to hyper-reactive malarial splenomegaly and splenic lymphoma with villous lymphocytes. PATIENTS: Forty-four patients, residents of the Ashanti region of Ghana that is hyperendemic for Plasmodium falciparum malaria, were studied. All patients had splenomegaly greater than 10 cm. They were given proguanil 100 mg/day for a minimum of 6 months. Lymphocyte surface phenotypes were studied on the peripheral blood smears, immunoglobulin gene rearrangement by the Southern blot technique, serum IgM concentration using the Nor-Partigen-IgM kit, and serum paraprotein concentration by electrophoresis. RESULTS: Based on the response to proguanil, the patients were categorized into good respondents, partial respondents, and non respondents. Peripheral blood lymphocytes exceeded 30% in 19, and villous lymphocytes were less than 30% in 25 patients. CONCLUSION: Splenic lymphoma with villous lymphocytes may be difficult to differentiate from the African variant of chronic lymphocytic leukemia which is associated with splenomegaly and from hyperreactive malarial splenomegaly with lymphocytosis. In West Africa, a peripheral blood lymphocyte count greater than 10 x 109/L, with more than 30% of villous lymphocytes and failure of splenic regression with anti-malarial therapy suggest a diagnosis of splenic lymphoma with villous lymphocytes.

Adolescent↗
PubMed1995

Detection and characterization of seven novel protein S (PROS) gene lesions: evaluation of reverse transcript-polymerase chain reaction as a mutation screening strategy.

The molecular genetic analysis of protein S deficiency has been hampered by the complexity of the protein S (PROS) gene and by the existence of a homologous pseudogene. In an attempt to overcome these problems, a reverse transcript-polymerase chain reaction (RT-PCR) mutation screening procedure was developed. However, the application of this mRNA-based strategy to the detection of gene lesions causing heterozygous type I protein S deficiency appears limited owing to the high proportion of patients exhibiting absence of mRNA derived from the mutation-bearing allele ("allelic exclusion"). Nevertheless, this strategy remains extremely effective for rapid mutation detection in type II/III protein S deficiency. Using the RT-PCR technique, a G-to-A transition was detected at position +1 of the exon IV donor splice site, which was associated with type I deficiency and resulted in both exon skipping and cryptic splice site utilization. No abnormal protein S was detected in plasma from this patient. A missense mutation (Asn 217 to Ser), which may interfere with calcium binding, was also detected in exon VIII in a patient with type III protein S deficiency. A further three PROS gene lesions were detected in three patients with type I deficiency by direct sequencing of exon-containing genomic PCR fragments: a single base-pair (bp) deletion in exon XIV, a 2-bp deletion in exon VIII, and a G0to-A transition at position -1 of the exon X donor splice site all resulted in the absence of mRNA expressed from the disease allele. Thus, the RT-PCR methodology proved effective for further analysis of the resulting protein S-deficient phenotypes. A missense mutation (Met570 to Thr) in exon XIV of a further type III-deficient proband was subsequently detected in this patient's cDNA. No PROS gene abnormalities were found in the remaining four subjects, three of whom exhibited allelic exclusion. However, the father of one such patient exhibiting allelic exclusion was subsequently shown to carry a nonsense mutation (Gly448 to Term) within exon XII.

Base Sequence↗
PubMed1995

Three novel mutations in the protein C (PROC) gene causing venous thrombosis.

Missense mutations, three of them novel (Gly47-->Cys, Arg178-->Pro, Ala259-->Thr), were found in the protein C genes of four patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX and the use of a molecular model of protein C provided explanations as to how these lesions might alter either the structure, function or stability of the protein C molecules encoded.

Adolescent↗
PubMed1992

Unique expression of von Willebrand factor by type IIA von Willebrand's disease endothelial cells.

Endothelial cells (EC) were cultured from the umbilical cord of a male neonate whose mother was previously diagnosed with type IIA von Willebrand's disease (vWd). The diagnosis of type IIA vWd in the proband was confirmed by low ristocetin activity and the absence of the highest molecular weight (MW) forms of von Willebrand factor (vWf) in his platelet poor plasma. The vWf of EC cultured from the neonate's umbilical cord differed from that of control EC and the cell line EA.hy926 in two respects. Firstly, the full range of molecular weight forms was present in the patient EC lysate and, secondly, vWf:Ag expression was approximately seven-fold greater than that of control cells. Platelet lysates prepared from other affected members of the type IIA vWd family in the presence or absence of proteolytic inhibitors demonstrated a near normal vWf multimeric distribution. Resistance of these high MW forms to heat degradation was conferred by the presence of proteolytic inhibitors. Moreover, the full plasma vWf multimeric distribution could not be restored by the inclusion of EDTA. N-ethylmaleimide and leupeptin in the anticoagulant during the rapid preparation of platelet poor plasma. These findings lend support to the heterogeneous nature of type IIA vWd and has possible implications in the understanding of the intracellular processes involved in the biosynthesis and storage of the vWf macromolecular complex as well as the pathogenesis of type IIA vWd.

Blood Platelets↗
PubMed1991

The clinical effects of prolonged treatment of patients with advanced cancer with low-dose subcutaneous interleukin-2 [corrected].

Thirty-five patients with advanced malignant disease have been treated as outpatients with increasing doses (0.1-100 mcg) of interleukin 2 (IL2) by once daily self-administered subcutaneous (s.c.) injection, 5 days weekly for 8 weeks followed by a 4 week observation period. Systemic side effects were not experienced by patients at the 3 lower doses. Three patients required dose reduction from 100 mcg daily because of intolerance (fever, rash, lethargy, nausea and vomiting) and one patient was discontinued because of dyspnoea. We observed immunological effects at the 100 mcg dose (but not at the lower doses). These consisted of (a) a modest sustained lymphocytosis, (b) eosinophilia in six (out of nine) patients and (c) a significant rise in IL2-stimulated peripheral blood lymphocyte activated killer (LAK) cell activity in six (out of nine) patients to a mean of 2.0 times pretreatment levels (P less than 0.01). Two (out of nine) patients with renal cell carcinoma treated with 100 mcg daily had partial responses of duration 4 and 9 months respectively and a further three had disease stabilisation for at least 3 months. Low dose long-term s.c. IL2 is clinically and immunologically active, and in comparison to other IL2 regimens it has minor toxicity and is easy to administer. These characteristics make low dose s.c. IL2 suitable for study in the adjuvant setting.

Adult↗
PubMed1990

In vivo imaging of rat lymphocytes with an indium 111-labelled anti-T cell monoclonal antibody: a comparison with indium 111-labelled lymphocytes.

An indium 111-labelled mouse anti-rat T cell monoclonal antibody, MRC OX-19, was injected intravenously into rats to establish the usefulness of radiolabelled anti-lymphocyte antibodies in imaging lymphoid tissues. Antibody binding in vivo, measured by immunofluorescence analysis of cell suspensions made from lymphoid tissues, was detectable on lymphocytes in blood, spleen and lymph nodes. The extent of binding was time and antibody-dose dependent. Doses of antibody above 80 micrograms/kg body weight resulted in modulation, i.e. loss of CD 5 (T1) molecules from the cell surface, although the cells remained in the circulation. Modulation was demonstrable within 2 h and for at least 24 h after a single injection of antibody. Intravenous injection of 111In-MRC OX-19 resulted in levels of in vivo binding comparable with those seen with unlabelled antibody. Scintillation imaging showed early splenic localisation persisting over 48 h, a more gradual localisation in the lymph nodes seen clearly at 24 h and a steady background. Comparison of the in vivo distribution of labelled antibody and 111In-tropolone-labelled lymphocytes showed that both could be used for external imaging of lymphocytes by scintillation camera.

Animals↗