The attitudes of relatives to autopsy: a misconception.

AIM: Hospital autopsy rates have been falling steadily over recent decades. One factor that has been implicated in this decline is the perception that the general public views postmortem examinations unfavourably and that this often makes clinicians reluctant to discuss autopsy with families and seek their consent. The aim of this study was to test this assumption. OBJECTIVES/METHODS: In the division of lymphoid malignancies at St Bartholomew's Hospital, we suggested autopsy and discussed it in depth with the families of all the patients who died in hospital in an 8-month period in order to assess whether the autopsy rate could be increased by improving the approach to the relatives. RESULTS: Consent for a postmortem examination was requested in 18 of 23 cases and granted in 16 cases, giving a consent rate of 89%, and an overall rate of autopsy of 69.5%. CONCLUSION: The attitude of the general public is positive overall, and translates into high autopsy rates when the value of the examination is presented honestly and the details of the procedure are adequately explained.

AZD1152 rapidly and negatively affects the growth and survival of human acute myeloid leukemia cells in vitro and in vivo.

Aurora kinases play a critical role in regulating mitosis and cell division, and their overexpression has been implicated in the survival and proliferation of human cancer. In this study, we report the in vitro and in vivo activities of AZD1152, a compound that has selectivity for aurora B kinase, in acute myeloid leukemia (AML) cell lines, primary AML samples, and cord blood cells. AZD1152 exerted antiproliferative or cytotoxic effects in all cell lines studied, inhibited the phosphorylation of histone H3 (pHis H3) on Ser10 in a dose-dependent manner, and resulted in cells with >4N DNA content. THP-1 cells treated with AZD1152 accumulated in a state of polyploidy and showed a senescent response to the drug, in contrast to the apoptotic response seen in other cell lines. Accordingly, AZD1152 profoundly affected the growth of AML cell lines and primary AML in an in vivo xenotransplantation model. However, concentration-dependent effects on cell growth, apoptosis, and cell cycle progression were also observed when human cord blood and primary lineage-negative stem and progenitor cells were analyzed in vitro and in vivo. These data suggest that the inhibition of aurora B kinase may be a useful therapeutic strategy in the treatment of AML and that further exploration of dosing and treatment schedules is warranted in clinical trials.

Patterns of recruitment into acute myeloid leukaemia (AML) 15 and outcome for young patients with AML at a single referral centre.

This study assessed the recruitment to an acute myeloid leukaemia (AML) trial (AML15) in a single centre, evaluated whether outcome was influenced by trial entry and whether the trial population could be considered representative of all AML patients by retrospective comparison of patient characteristics, trial entry and outcome for 81 consecutive patients (<60 years). All patients were considered for trial entry, however the trial was not offered to 12 (15%) patients. These patients had a worse outcome than the 69 (85%) patients that were invited to participate (P = 0.04). Sixteen patients (23%) invited to participate in the trial declined and were treated on equivalent protocols. These patients had a similar outcome to those who accepted entry into the trial (P = 0.2). These results suggested that physicians exert a selection bias when evaluating patients for trial entry. Thus the overall survival estimates generated from large phase III trials may indicate that the outcome for patients with AML is better than the outcome experienced in the 'real' world. Furthermore, patients who are considered appropriate for randomization into a trial, but decline entry, experience a similar outcome to those treated on trial when treated in an equivalent manner.

Follicular lymphoma international prognostic index.

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs < or = 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs > or = 120 g/L), number of nodal areas (> 4 vs < or = 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk (> or = 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.

The human type-C retrovirus, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma

Type-C RNA tumour viruses have been implicated in the etiology of naturally occurring leukemias and lymphomas of animals. Human T-cell leukimia/lymphoma virus (HTLV) is the first human virus of this class consistently identified in association with a specific type of human leukemia/lymphoma. The isolation of HTLV was made possible by the ability to grow mature T-cell in tissue culture usually with T-cell growth factor (TCGF). We now report a cluster usually with T-cell leukemia/lymphoma among Blacks from the Caribbean in which all eight cases are positive for HLV virus and/or antibody. These patients have diseases that appears indistinguisable from Japanese adult T-cell leukemia/lymphoma which, as we have also reported, is associated with HTLV in over 90 percent of cases. The finding of HTLV antibodies in some of the normal population in the Caribbean and Japan, and the clustering of a specific form of T-cell leukemia/lyphoma in these virus-endemic areas, suggest that HTLV infection may be associated with the occurrence of a distinctive clinico-pathologic entity (Summary)