Treatment of children with histiocytosis.
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Biomedical subjects
Publications and source records attributed to M M Reid.
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To assess the usefulness of immunocytochemical analysis of bone marrow in patients with neuroblastoma, marrow smears from 33 staging procedures in 12 patients were examined using an indirect immunoalkaline phosphatase technique with monoclonal antibodies raised against human neural tissue. Marrow aspirate and trephine collagenase digest specimens from individual sites were each tested with the monoclonal antibody UJ13A and with a pool of three related antibodies. The results were compared with morphological assessment of conventionally stained aspirates and trephine specimens taken at the same time. Immunostaining suggested the presence of tumour in seven of 18 staging procedures in which conventional techniques had shown infiltration. Tumour infiltration was also suggested in four of 10 staging procedures with suspicious trephine specimens, but in none of three with relatively innocent histological and cytological features. Immunological investigation provides no additional information about the presence of infiltration if conventional microscopy has shown definite tumour. When histological appearances are suspicious, immunostaining of stored aspirate smears or collagenase digest specimens may provide evidence of infiltration. There are insufficient data to comment on the value of immunostaining when conventional techniques reveal "normal" marrow, but the impression gained from this study is that immunostaining has a limited role in the detection of metastatic neuroblastoma, which yet remains to be defined.
Frozen sections from bone marrow trephine biopsy specimens from children with disseminated neuroblastoma were stained using the monoclonal antibody UJ13A. An immunoalkaline phosphatase technique was the preferred staining method. Acceptable histological detail was obtained from this material and deposits of tumour cells detected. Some apparently fibrous tissue was also stained by this antibody. The results show that this immunohistological approach is feasible and provide encouragement for its addition to the range of investigations currently available for assessing the marrows of children with this disease.
Over three years 81 consecutive bone marrow transplant recipients (32 allogeneic and 49 autologous) who received prophylaxis with acyclovir, were studied for symptomatic virus infection. Thirty nine infections were documented in a total of 28 patients. Thirty two infections were mild, five were moderately severe, and two were severe. Cytomegalovirus infection occurred in only six allogeneic recipients. Herpes simplex virus and varicella zoster virus infections occurred infrequently. Seven patients who were considered at the time of death to have died due to an infectious cause were studied virologically at necropsy. In only one patient was a virus infection thought to have been the cause of death. Prophylaxis with acyclovir may have influenced the rate and clinical prominence of herpes virus infections. In this study viruses were considered to have had a relatively minor role in causing morbidity and mortality.
At least 16 cases of inversion tandem duplications of the short arm of chromosome 8 have been reported. Structural rearrangements of chromosome 8 have made it possible to localise the gene for glutathione reductase (GSR) to 8p21.1. We report here on a 16 month old boy with mental retardation with partial trisomy 8 owing to a de novo inv dup(8)(p12----p23.1).
Fetal hydrops (hydrops fetalis) remains a significant cause of fetal and neonatal mortality. The decreased incidence of rhesus iso-immunisation due to prophylaxis with rhesus immune globulin (anti-D), improved antenatal ultrasound screening, and advances in neonatal intensive care have greatly altered the clinical outlook in this condition. A retrospective review of all 27 liveborn cases of hydrops in the Royal Maternity Hospital, Belfast in the period 1974-89 showed that in the last five years 40% of cases were non-immune in origin. The mortality rate fell from 100% in the first part of the study to 50% in the second.
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Doppler ultrasound measurements of pulmonary blood flow in 20 babies with severe respiratory distress syndrome treated in a randomised controlled trial of surfactant replacement showed that the immediate improvement of oxygenation was not associated with a significant increase in pulmonary blood flow. Reduction in ventilator settings and increases in the extent of chest wall movements measured by a cardiorespiratory monitor suggested that the improvement after surfactant had been given was a result of alveolar stabilisation and increased pulmonary compliance. Further simultaneous studies of pulmonary blood flow and pulmonary compliance are needed to confirm these findings.
Bone marrow trephine biopsy specimens were obtained at diagnosis from 63 of 76 consecutively presenting children with acute lymphoblastic leukaemia (ALL). The association between marrow fibrosis and presenting features, including immunophenotype, was analysed. Reticulin was increased in 45 of 56 cases in which blasts expressed B lineage markers, but in only one of seven with T-ALL. A weak association was also found between marrow fibrosis and splenomegaly in those with common ALL. Marrow fibrosis is apparently associated with some examples of ALL of B cell lineage, but precisely which subtypes and whether the phenomenon is clinically important remain to be determined.
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A child with disseminated Ewing's sarcoma underwent cytogenetic investigations which showed different structural rearrangements of chromosome 22 at diagnosis (?ring22), and at relapse [t(10;22)], but the classic translocation t(11;22) was not detectable. This case provides further evidence of the importance of chromosome 22 in this disease, while raising some questions about the central importance of the translocation between chromosomes 11 and 22.
This study has demonstrated the ability of human bone marrow natural killer (NK) cells to inhibit the formation of granulocyte-macrophage colonies from autologous bone marrow derived committed progenitors in vitro. NK cell activity was demonstrated in all marrow samples and could be significantly increased by pretreatment of the bone marrow mononuclear cells with IFN-alpha. Bone marrow preincubated with IFN-alpha produced significantly fewer colonies in both Day 7 and Day 14 colony assays compared with untreated marrow. Removal of active NK cells by Leu 11b and complement significantly increased the number of colonies observed in both Day 7 and Day 14 assays, but this was not the case when NK cell-depleted marrow was treated with IFN-alpha prior to the GM assays. These results have further shown that NK cells and IFN-alpha are involved in regulating granulopoiesis by demonstrating that IFN-alpha can inhibit granulocyte/macrophage colonies in the presence or absence of NK cells in the bone marrow.
A 16-year-old boy with leukemia had a marked leucocytosis (165 x 10(9)/L) at presentation. The large number of neutrophils, myelocytes, and metamyelocytes and negative leucocyte alkaline phosphatase reaction raised the possibility of chronic myeloid leukemia. Cytogenetic analysis showed a deletion of chromosome 7, a t (8;21), a missing Y chromosome, and, in some cells, duplication of the der(21). The Philadelphia chromosome was not detected, nor was the breakpoint cluster region of chromosome 22 found to be rearranged. Myeloid leukemia with t (8;21) can therefore be associated with a greater degree of granulocytic hyperplasia than has so far been apparent, and cytogenetic analysis in this case has been crucial in distinguishing leukemia types.
One hundred and eighty bone marrow trephine biopsies obtained during 68 staging procedures before and during treatment of 20 children with Stage IV neuroblastoma were reviewed. A primitive cell infiltrate with prominent fibrous stromal reaction and increased reticulin characterized the marrow at presentation. Once treatment had begun, primitive cells became difficult to find but fibrosis and a marked increase in reticulin persisted in most cases. Distortion in marrow architecture and the continuation of abnormal stromal reactions may reflect failure to eradicate tumour despite absence of detectable primitive cells. If current therapeutic options are to be assessed properly, uniformly accepted criteria to define continuance of marrow infiltration in children with neuroblastoma are needed. A scheme for classifying marrow histological appearances is presented which may prove to be of more value than a simple distinction between 'involved' and 'uninvolved'.
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As part of a multicentre study of porcine surfactant administration in respiratory distress syndrome, 29 babies weighing 2000 g or less were studied in the neonatal intensive care unit of the Royal Maternity Hospital, Belfast. Fourteen babies of a mean gestational age of 28.1 weeks were randomly allocated to the treatment group (200 mg/kg phospholipid given intratracheally) and 15 babies of a mean gestational age of 28.7 weeks formed the control group. All babies had severe respiratory distress syndrome (oxygen requirement over 60%, mechanical ventilation, and age 15 hours or less). Almost immediate improvement in oxygenation was seen in the treated group so that oxygen concentrations could be reduced and remained significantly lower than those of control babies for the first seven days of life. Alveolar-arterial oxygen gradients were also significantly different for the first five days after treatment. More babies in the treatment group survived (79% v 40%) but the difference was not significant. The incidence of pneumothorax and of intraventricular haemorrhage, however, was significantly lower in treated babies compared with controls. For babies weighing less than 1200 g the risk of developing or extending intraventricular haemorrhage after entry to the study was also reduced in the treatment group (29% v 100%).
The association of non-random chromosome abnormalities with solid tumours of childhood may improve accuracy of diagnosis and prognosis and lead to a better understanding of their biology. In a pilot study in the Northern region of England fresh tumour biopsy specimens were obtained from 39 to 72 consecutive solid tumours in children who presented over a period of 21 months. Cytogenetic analysis was possible in 33 and clonal chromosomal abnormalities were detected in nine. In addition, seven of 10 tumours investigated after treatment were abnormal. Ten of these 16 abnormal karyotypes have not previously been described. This pilot study has shown that a concerted investigation of tumour cytogenetics is possible. A multicentre study is essential if our knowledge of basic tumour cytogenetics is to progress.