Differential cytology of bronchoalveolar lavage fluid.
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Biomedical subjects
Publications and source records attributed to M M Reid.
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Central review of bone marrow trephine biopsies obtained between January 1990 and July 1996 from 282 children with neuroblastoma showed that 18% of cores from older children and an unacceptably high 36% from infants were inadequate (p = 0.0002). Centres should choose their operators for this invasive investigation of infants with more care in order to reduce the failure rate.
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AIMS: To evaluate success in obtaining adequate bone marrow trephine biopsy cores from children. METHODS: Sections of trephine biopsy cores submitted by 25 centres from children with neuroblastoma over a five year period were reviewed centrally. In cores containing no tumour adequacy was defined as 0.5 cm of well preserved bone marrow after processing. Occasional smaller cores containing obvious tumour were also considered adequate. RESULTS: Of 822 biopsy specimens, 139 (17%) were inadequate. In 13 centres submitting at least 20 cores failure rates ranged from 2.6 to 50%. There was no improvement over the five years of the study. There was no practically important correlation between the numbers of cores submitted and success in obtaining adequate specimens. Although a lower rate of inadequate biopsy specimens was found when haematologists rather than paediatricians (13 v 29%) were the predominant operators this should not be overinterpreted, not least because of the potentially confounding association between haematologist operators and larger numbers of biopsy specimens, and because the arbitrary subdivision of centres according to operator specialty was crude. The skill of individual operators could not be assessed. CONCLUSIONS: Many operators do not obtain adequate bone marrow biopsy specimens from children. Improvement is necessary because this is an invasive investigation, often performed under general anaesthesia. Reporting pathologists are well placed to influence practice by pointing out inadequacies in the specimen and suggesting retraining or even a change in operator. Improvement would almost certainly occur if this investigation was restricted to locally recognised successful operators, whatever their specialty. Most centres should review their practice and devise strategies to improve their ability to obtain adequate cores.
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In order to achieve some uniformity in histological detection of bone marrow infiltration by neuroblastoma and to provide a measure of variation in histological opinions, sections from 712 evaluable trephine biopsy cores from children in a European Neuroblastoma Study Group (ENSG) study were reviewed centrally. Biopsy specimens were graded as tumour positive or negative. Discordance between local and central review opinions was found in 5% of specimens. Only five of 165 children at presentation and nine of 256 re-staging procedures in 126 children, affecting one child each, had their diagnosis upgraded to positive. In six re-staging procedures, affecting one child each, the diagnosis was downgraded. The low discordance rate is encouraging and substantially less important than previously documented difficulties in obtaining adequate specimens.
We report a child with a progressive "solid alveolar rhabdomyosarcoma" in whom analysis of tumor cells revealed a t(2;13) translocation characteristic of the classical alveolar subtype. Both subtypes of alveolar rhabdomyosarcoma are associated with a poor response to treatment and the occurrence of this translocation in both is suggestive of a common biologic origin.
Although the potential for prisons to act as the setting for HIV transmission has been recognised, there is an enduring lack of knowledge in this area. Data are presented on patterns of injecting and sharing in Edinburgh prison (Scotland), 1993-1994. There was a relatively low level of injecting in Edinburgh prison during this period, with 13% (8/60) of a sample of drug users having injected at some point during their current sentence. The majority (6/8) of those who had injected had shared injecting equipment. Where sharing took place, the level of HIV risk was variable, but would have been higher had cleaning fluids not been available within the prison, or had they not been used by sharers. The implications of this study for drug service provision in prisons is discussed.
The prognosis of acute lymphoblastic leukaemia (ALL) in adults is poor compared with children in terms of complete remission (CR) and leukaemia-free survival. In children in vitro resistance of leukaemic cells to various cytotoxic agents is an independent poor prognostic marker, but the relevance of in vitro drug resistance in adults to poor prognosis has not been described. Lymphoblasts from 16 adults and 32 children with ALL at initial presentation were assayed for in vitro drug sensitivity in a short-term culture system using the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as an indicator of cell viability. The following drugs were tested: prednisolone, daunorubicin, mitozantrone, etoposide, melphalan and 6-thioguanine. At initial presentation, lymphoblasts from adults demonstrated a significantly higher degree of in vitro resistance to prednisolone than those from children (P < 0.01). Glucocorticoid resistance may be a fundamental difference between adult and childhood ALL which may underlie different biological aspects and also explain the difference in prognosis. Lymphoblasts from adults who achieved CR were more sensitive in vitro to prednisolone (P = 0.07), daunorubicin (P < 0.05), mitozantrone (P < 0.01) and melphalan (P < 0.05) than cells from those who did not. The MTT assay can predict response to induction chemotherapy in adults and therefore discriminate between standard- and high-risk patients. The assay, however, is not suitable for selection of the most effective agent for treatment because of in vitro cross-resistance of lymphoblasts to various drugs tested.
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In order to determine incidence, outcome, trends in management and natural history, data on 92 children with chronic idiopathic thrombocytopenic purpura (ITP), comprising 66 from a single centre's experience between 1950 and 1980 and all 26 presenting from a defined population between 1984 and 1994, have been analysed. Its incidence, calculated from the population based group, is 0.46/10(5) children per year. Twenty nine of 34 (85%) remitted after splenectomy. Short initial histories predicted response to splenectomy. Splenectomy was offered only half as frequently in the last 10 years as in the 30 year, single centre group of children. Most (39 cases) of those not offered or successfully treated by splenectomy recovered spontaneously. The predicted spontaneous remission rate in 85 with adequate follow up data is 61% after 15 years. No other form of active treatment was of lasting benefit. No death solely attributable to chronic ITP occurred. The high spontaneous recovery rate, low mortality, and generally benign outcome may encourage a less interventionist approach to management.
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A patient with sideroblastic anaemia, development delay, and trichothiodystrophy is presented. Trichothiodystrophy is a feature of several autosomal recessive diseases. Photosensitivity, failure to thrive, and developmental delay are commonly observed in affected cases. X linked inheritance accounts for the bulk of cases with sideroblastic anaemia. This case highlights the importance of routine hair microscopy in cases of atypical ectodermal dysplasia.
A 4-year prospective study of de novo acute myeloid leukaemia in patients aged 56 years and over was undertaken in the Northern Region of England (population 3.09 million). The study was conducted to assess the incidence and outcome of treatment in all elderly patients diagnosed between January 1, 1988 and December 31, 1991. Two hundred cases de novo AML were confirmed, giving an incidence of 6.05/10(5) per annum (age specific population) (95% Cl, 5.2-6.9). Acute promyelocytic leukaemia was rare. Erythroleukaemia, monocytic leukaemia and AML with trilineage myelodysplasia were more common than in younger patients. Karyotypic abnormalities classically associated with response to therapy were present in only six of 91 patients where cytogenetic data was available. Treatment was at the discretion of the physician in charge: if given, specific treatment was recorded and clinical outcome assessed. Only 84 (42%) of patients received treatment with curative intent. Forty-four of 84 achieved a complete remission, usually of brief duration. A normal karyotype in leukaemic cells was associated with a survival advantage in this group (p < 0.05). Actuarial overall survival at 4 years for the entire group was 2.5%. Even with aggressive treatment, the outcome is poor. The pattern of disease and its lack of response to conventional treatment would support the hypothesis that AML in the elderly may differ biologically from that observed in younger patients. Karyotyping appears to predict those patients likely to benefit from intensive therapy and decisions about management in otherwise fit patients should, if possible, be delayed until a result is obtained. Every effort should be made to give such patients optimal treatment. However, most patients are unsuitable for aggressive treatment and, since long-term survival is rare, cure should not be offered as an inducement to accept such treatment and improving quality of life outside hospital should be the aim of treatment in this group.
The aim of this study was to collect prospectively unselected, population-based data on young adults with acute myeloid leukaemia (AML) over a 9-year period and to evaluate the impact on survival of the introduction of allogeneic transplantation performed in first remission. The population within the Northern Region of England is 3.09 million. During the study period a total of 149 de novo patients between 15 and 55 years old presented. The incidence of AML was 0.79 per 10(5) (age-specific population) in the 15-24-year-old group, 0.85 per 10(5) in the group 25-39 years old and 1.35 per 10(5) in the 40-55-year-old group. Remission induction success varied with age (74% for patients < 40 years and 58% for patients 40-55 years). In the 15-40 year old group 28 patients had an HLA-matched donor, 22 patients had a transplant (one syngeneic) and 24 patients in the 15-40-year-old group in remission at 6 months did not have a transplant. The allogeneic group < 40 years old had an event-free survival (EFS) at 4 years of 62%, whereas patients of the same age who received chemotherapy alone had an EFS at 4 years of 24%. A small heterogeneous group of 14 patients who had intensification with autotransplant are not included in this analysis. The population study approach demonstrates the difficulties of introducing uniform treatment strategy in this disease group. The study confirms the view that allogeneic transplant in first remission in the 15-40-year-old group is the treatment of choice. Unfortunately the overall impact of transplant on the population is not great since only 22 of 149 patients (14%) were able to receive an allograft in first remission.
Expression of the main classes (pi, mu, and alpha) of glutathione S-transferase (GST) was assessed in the blasts of children presenting with acute lymphoblastic leukemia using an immunohistochemical technique. Bone marrow trephine biopsies obtained at presentation from 71 cases were studied (42 boys, 29 girls; age range, 6 months-14 years; median age, 4 years) and expression was correlated with event-free survival. The period of follow-up was 12-108 months, during which time 21 patients (30%) relapsed. All the samples examined were negative for alpha class GST. Samples from 8 patients, all of whom remained in remission at the time of analysis, were found to be negative for pi class GST at presentation. Samples from 44 (patients were negative for mu class GST (62%); of these, 36 patients (82%) remained in remission. In comparison, of the 27 patients who were positive for mu class GST, only 14 (52%) remained in remission. Analysis of event-free survival demonstrated that expression of mu class GST predicts a 3-fold increased risk of relapse (95% confidence interval, 1.25-7.26). This risk factor appears to be independent of other recognized prognostic factors.
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