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C Bunch

Publications and source records attributed to C Bunch.

At least 19 recordsLinked to original sources
PubMed2001

Clinical ethics support services in the UK: an investigation of the current provision of ethics support to health professionals in the UK.

OBJECTIVE: To identify and describe the current state of clinical ethics support services in the UK. DESIGN: A series of questionnaire surveys of key individuals in National Health Service (NHS) trusts, health authorities, health boards, local research ethics committees and health professional organisations. Interviews with chairmen/women of clinical ethics committees identified in the surveys. SETTING: The UK National Health Service. RESULTS: Responses to the questionnaires were received from all but one NHS trust and all but one health authority/board. A variety of models of clinical ethics support were identified including twenty formal clinical ethics committees (CECs). A further twenty NHS trusts expressed an intention to establish a CEC within the next twelve months. Most CECs in the UK have been in existence less than five years and are still defining their role. The chairmen identified education of committee members and contact with other ethics committees as important requirements for committee development. Problems were identified around lack of support for the committee and with raising the profile of the committee within the institution. There has been little evaluation of clinical ethics support services either in the UK or in other countries with longer established services. What evaluation has occurred has focused on process rather than outcome measures. CONCLUSIONS: Clinical ethics support services are developing in the UK. A number of issues have been identified that need to be addressed if such support services are to develop effectively.

Attitude of Health Personnel↗
PubMed1998

The role of maternal hostility and family environment upon cardiovascular functioning among youth two years later: socioeconomic and ethnic differences.

Two hundred sixty-eight African-American and white children and their biological mothers participated in the study. The purpose of the study was to examine the potential collective impact of maternal hostile coping styles and perceptions of family functioning upon youths' cardiovascular (CV) functioning 2.4 years later, within the context of SES and ethnicity. The mother completed a set of questionnaires that included the Cook-Medley Hostility Scale and three scales from the Family Environment Scale (FES). Childrens' systolic and diastolic blood pressure (SBP and DBP) and impedance cardiography derived total peripheral resistance (TPR) was measured at rest two years later. Mothers with lower SES and African-American mothers reported higher levels of hostility compared to those with higher SES and white mothers, respectively. Lower SES mothers reported lower levels of family cohesion and expressiveness than higher SES mothers. Whites reported more family conflict and expressiveness than African Americans. African-American and lower SES youth exhibited higher SBP and DBP values than whites and higher SES youth. Among lower SES African-American youth, CV functioning tended to be impacted negatively when their mothers rated themselves high in hostility. Findings suggest that ethnicity and SES may have independent as well as interactive impacts on the influence of maternal coping styles on the CV functioning of their children, particularly those from lower SES backgrounds.

Adaptation, Psychological↗
PubMed1996

Demonstration of developing myelodysplasia/acute myeloid leukaemia in haematologically normal patients after high-dose chemotherapy and autologous bone marrow transplantation using X-chromosome inactivation patterns.

Autologous bone marrow or peripheral blood stem cell transplantation may carry an increased risk of secondary myelodysplasia (MDS) and acute myeloid leukaemia (AML), which are already recognized as complications of conventional treatment for lymphoid malignancies. In order to ascertain whether it is possible to detect the evolution of such a clone at an early stage in its development we have studied X-chromosome inactivation patterns (XCIPs) in three informative females who developed abnormal myelopoiesis after high-dose chemotherapy and ABMT. In one patient transplanted for relapsed Hodgkin's disease a leukaemic clone comprising approximately 50% of the patient's myeloid cells was detectable by comparison of peripheral blood granulocyte and T-cell XCIPs when the full blood count and morphology were normal. She presented with AML 7 months later. In two patients transplanted for AML, XCIP analysis was complicated by constitutively skewed Lyonization patterns, nevertheless a progressive alteration could be demonstrated by serial analyses. In one patient a difference was detectable 28 months before presentation with MDS. In the other patient, despite evident mild pancytopenia and alterations in her XCIPs over the past 4 years, she has developed no definitive myelodysplastic features and oligoclonality due to stem cell failure cannot be excluded. These studies show that XCIPs can be used to predict development of MDS/AML in some patients, but the technique is limited by technical variability and frequent constitutional skewing in the haemopoietic system.

Acute Disease↗
PubMed1995

Immunological factors and risk of infection in plateau phase myeloma.

AIMS: A series of patients with myeloma were investigated to assess whether immunological risk factors predisposing to serious infection could be identified. METHODS: Patients (n = 102) with predominantly plateau phase myeloma were monitored prospectively for infections. Immunological parameters including total non-paraprotein immunoglobulins and specific antibody titres were measured in all patients and compared with a control population of healthy individuals of a similar age; response to immunisation with Pneumovax II, tetanus and diphtheria toxoids and IgG subclasses were measured in a subgroup of 41 patients. Other characteristics investigated for any association with infection included age, sex, paraprotein type, disease stage, and chemotherapy. RESULTS: Specific antibody titres to pneumococcal capsular polysaccharides and tetanus and diphtheria toxoids were significantly reduced compared with the control population. Low antipneumococcal and anti Escherichia coli titres correlated with risk of serious infection and low anti-pneumococcal titres with severity of non-paraprotein immunosuppression. In 41 immunised patients responses to Pneumovax II, tetanus and diphtheria toxoids were poor; IgG subclass levels were significantly reduced and a poor IgG response to Pneumovax II immunisation was associated with an increased risk of septicaemia and low IgG2 levels. The overall serious infection rate was 0.92 infections per patient year and was four times higher during periods of active disease (1.90) compared with plateau phase myeloma (0.49). The predominant site of infection was the respiratory tract. Clinical and laboratory parameters showed only male sex and reduced non-paraprotein IgG and IgA levels to be significantly associated with at least one serious infection. CONCLUSIONS: A subgroup of patients with myeloma with poor IgG responses to exogenous antigens, who are at increased risk of serious infection, can be identified and may benefit from replacement immunoglobulin therapy to reduce the risk of infection.

Aged↗
PubMed1994

Focal adhesion kinase expressed by nerve cell lines shows increased tyrosine phosphorylation in response to Alzheimer's A beta peptide.

A beta is a 39-43-amino acid peptide that accumulates as extracellular aggregates in Alzheimer's disease-afflicted brain tissue. Contact between these aggregates and neurons is potentially pathogenic, although little is known about the cellular transduction mechanisms. We have investigated the impact of A beta aggregates on the neuronal control of protein tyrosine phosphorylation, which underlies signal transduction for multiple families of growth factor and adhesion receptors. Added to cultures of rat and human nerve cell lines, A beta aggregates evoked a non-desensitizing increase (1.3-3.6-fold) in tyrosine phosphorylation in a band at 118 kDa. The 118-kDa protein was determined by immunoprecipitation to be pp125FAK, not previously documented in cells of neuronal lineage. Immunoblots with anti-focal adhesion kinase (FAK) showed that A beta aggregates had no effect on FAK protein levels. The increase in FAK tyrosine phosphorylation occurred at doses of A beta aggregates that evoked lactate dehydrogenase release; evoked tyrosine phosphorylation preceded the first detectable lactate dehydrogenase release by 4 h. Like degeneration, the FAK response was dependent on A beta aggregation and neuronal differentiation. Since tyrosine phosphorylation of FAK is essential to its activity as a transduction component of integrin-, peptide-, and lysophosphatidic acid-mediated signaling, the data establish a link between A beta aggregates and signal transduction pathways implicated in diverse cell functions including neurite outgrowth, control of the cell cycle, and apoptosis.

Amino Acid Sequence↗
PubMed1994

Immunoglobulin replacement in patients with chronic lymphocytic leukaemia: a comparison of two dose regimes.

Previous studies have shown that intravenous immunoglobulin (IVIg) therapy is useful prophylaxis against infection in patients with secondary hypogammaglobulinaemia due to a low-grade lymphoproliferative disease. This randomized double-blind study was undertaken to determine prospectively the dose regime required. 34 such patients received IVIg at either 500 or 250 mg/kg every 4 weeks for 1 year. There was no significant difference in the rates of serious infections between the two groups of patients, which were well matched for disease and laboratory parameters. The rates of infection seen were similar to those in IVIg groups of previous studies and strikingly different from those in the placebo group in the previously randomized placebo-controlled study.

Aged↗
PubMed1992

Epstein-Barr virus-associated anaplastic large cell lymphoma in renal transplant patients.

A novel association, Epstein-Barr virus-positive Ki-1+/CD30+ anaplastic large cell non-Hodgkin's lymphoma of B-cell phenotype in immunosuppressed renal transplant recipients is reported. Case 1 involved an aggressive clinical evolution, whereas case 2 followed a more "benign" clinical course. Both lymphomas were Epstein-Barr virus-positive as assessed by in situ hybridization, Southern blot, polymerase chain reaction, and immunohistochemical analysis. Both lymphomas contained a single clonal Epstein-Barr virus terminal-repeat fragment. In case 1, clonality was confirmed by the detection of bi-allelic immunoglobulin (Ig) heavy chain gene rearrangement. Case 2 showed germline Ig genes at presentation and oligoclonal Ig heavy chain gene rearrangements at relapse. These results are consistent with the notion that anaplastic large cell lymphoma might arise in a B cell transformed by Epstein-Barr virus at a very early stage, before Ig gene rearrangement. The latter may occur later in the course of clonal evolution, thus permitting investigators to trace intermediate and late stages within a process of multistep lymphomagenesis and/or tumor progression.

Adolescent↗
PubMed1992

Predictors of infection in chronic lymphocytic leukaemia (CLL).

A group of patients with chronic lymphocytic leukaemia (CLL) were studied to determine whether particular clinical and laboratory parameters might help to identify those patients at risk of recurrent infection who would benefit from immunoglobulin replacement therapy. The case notes of 59 patients were reviewed with regard to stage and duration of disease, chemotherapy and frequency of infection over the preceding 2 years. Serum IgG levels and specific antibodies to tetanus, diphtheria and pneumococcal capsular polysaccharide were measured at the end of the 2-year period. A group of 56 healthy age-matched volunteers were used as controls. Eighteen patients had severe or multiple infections during the study period, 11 patients had recurrent infections and the remaining 30 patients had only minimal infections. Overall, serum IgG levels were low in 32 patients but in none of the control group (P = 8.8 x 10(-11). However, less than half of those patients with hypogammaglobulinaemia suffered from severe or multiple infections. Specific antibodies to pneumococcal capsular polysaccharide were low in 23 patients compared with six of the control group (P = 4.9 x 10(-4)). The majority of patients with severe or multiple infections (13/18) had low levels of both total IgG and specific antibodies to pneumococcal capsular polysaccharide. However, in the groups of patients with less frequent infections, a higher proportion had low serum IgG than low pneumococcal antibody levels. Low levels of pneumococcal antibodies were particularly associated with severe or multiple infections (P = less than 0.00001).

Aged↗
PubMed1991

Hypogammaglobulinaemia in low grade B cell tumours; significance and therapy.

Bacterial infection is an important cause of morbidity and mortality in patients with B-cell tumors; this is related to their secondary hypogammaglobulinaemia. Two studies of intravenous replacement therapy [IVIg] have been performed in such patients: a crossover study over two years and a randomised, multicentre study over one year. Both involved infusions of IVIg [400 mg/Kg] or an equivalent volume of saline every three weeks for one year. In both studies, serious bacterial infections were considerably reduced by IVIg. Viral and fungal infections were uncommon. In the crossover study bacterial infections were more frequent in periods in which patients serum IgG levels were below the normal range [less than 6.4 g/l]. The sites of bacterial infection were similar in these studies to those in previously published reports, namely respiratory tract, skin, urinary tract and blood. There were a few mild adverse reactions which were related to the rate of infusion, but no serious toxic effects. Haematological parameters were not significantly changed by IVIg at this dose and disease progression did not appear to be changed.

Agammaglobulinemia↗
PubMed1989

A study of the transport of lithium across the erythrocyte membrane in vivo and of the effects of the ion transport inhibitors digoxin and dipyridamole.

1. We have given an oral load of lithium carbonate to healthy volunteers in order to investigate the transport of lithium across the erythrocyte membrane in vivo and the effects of known inhibitors of that transport. 2. Using this technique we have shown that pretreatment with either digoxin, an inhibitor of the sodium/potassium pump, or dipyridamole, an inhibitor of the anion transporter, does not alter the plasma or erythrocyte lithium concentration profiles, nor any of the pharmacokinetic variables derived from these data, and we conclude that these two transport pathways do not contribute significantly to the in vivo handling of lithium by erythrocytes. 3. We have also shown that erythrocyte lithium concentrations measured directly differ significantly from the predicted concentrations calculated using the two-compartment pharmacokinetic model which has been used in some earlier comparisons of in vitro and in vivo lithium handling. 4. We suggest that the in vivo administration of lithium carbonate may permit a specific measure of the in vivo activity of the sodium/sodium countertransport pathway.

Adult↗
PubMed1989

Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors.

A randomized crossover study of prophylactic immunoglobulin (IgG) therapy was performed in patients with chronic lymphocytic leukaemia (CLL) or non-Hodgkin's lymphoma (NHL). Twelve patients with hypogammaglobulinemia or a history of recurrent infections received infusions of IgG or placebo intravenously (IV) every 3 weeks for 1 year. They were then switched to the alternative preparation for another year. The number of serious bacterial infections was significantly less (P = .001; Mainland's cross-over method) in the months in which patients received IgG. Serious bacterial infections showed a trend to be associated with an IgG level less than 6.4 g/L (P = .046; Fisher's exact test).

Aged↗