Biomedical subjects
Publications and source records attributed to M M Reid.
Three patients with congenital hypothyroidism missed on routine screening due to normal low thyrotrophin concentrations in the neonatal period presented in later childhood. Clinicians should remain aware of hypothyroidism as a cause of morbidity in early childhood despite a national screening programme.
In six patients with thrombocytopenic purpura not cured by splenectomy platelets fell to less than 150 X 10(9)/l within six weeks of splenectomy. They 'failed to respond'. Two underwent splenunculectomy without improvement. Splenuculectomy offered little chance of improvement to published cases who failed to respond but may well be helpful after true relapse.
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Fifteen children with acute lymphoblastic leukaemia (ALL) in remission receiving maintenance chemotherapy and 12 ALL patients off treatment and in remission were tested for natural killer (NK) cell activity in vitro. Compared with a control population the children with ALL receiving maintenance chemotherapy had low levels of NK cell activity. This effect was not due to a specific reduction in NK cell numbers since proportions of mononuclear cells detected by the monoclonal antibodies HNK-1 (Leu-7) and Leu-11a were normal. Furthermore NK cell activity in patients could only be partially increased by pre-incubation of effector cells with interferon (alpha IFN). These studies confirm the lack of NK cell activity in children with ALL and show that this phenomenon is directly related to functional NK cell impairment. Our study has further shown that this effect is transient since ALL patients off treatment and in remission showed normal levels and augmentation of NK cell activity.
Nasal concentrations of leucocyte interferon measured immunoradiometrically were appreciably higher in children infected with influenza viruses than those infected with paramyxoviruses. Regardless of the infecting virus, leukaemic children produced normal amounts of interferon, but this appeared to have little effect on the duration of excretion of virus.
Over a ten-year period we have studied 75 cases of adult acute lymphoblastic leukaemia (ALL). Sixty of the cases were seen from 1979 to 1984 and represent an unselected series of all known cases in a region of 3 000 000 people. Study of these patients has given further insight into the heterogeneous, clinical and cytological nature of adult ALL. Three protocols have been used and results are presented indicating that conventional approaches to treatment in this disease are unsatisfactory. Not all patients could be entered on protocols but these patients are included to give the overall perspective of this disease in clinical practice. A new strategy is proposed which envisages abandoning traditional maintenance chemotherapy in favour of either allogeneic marrow transplant or autologous transplant in first remission in the post-consolidation phase. Preliminary results of this flexible approach are given.
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In a randomised, controlled trial of the effectiveness of artificial surfactant therapy 100 babies of less than 34 weeks' gestation were intubated at birth and received manual ventilation. The 49 babies in the treated group also received 30 mg dipalmitoylphosphatidylcholine and 3 mg high-density lipoprotein in a 5 ml suspension. There were no significant differences in mortality or in the incidence or severity of respiratory distress syndrome between the surfactant-treated and control groups as a whole or between subgroups divided on the basis of sex or pulmonary maturity (as assessed by the lecithin-sphingomyelin ratio). However, there appeared to be a trend towards improved survival in treated babies of 27-29 weeks' gestation.
A case of childhood T-cell acute lymphoblastic leukaemia (ALL) is presented in which the only chromosome abnormality at diagnosis was a deletion of part of the short arm of one chromosome 9 (9p-). Cytogenetic studies at relapse showed, in addition to 9p-, a partial deletion of the long arm of one chromosome 6 (6q-) and the Philadelphia chromosome (Ph1) produced as a result of the classical translocation t(9q+;22q-). All metaphases from haemopoietic colonies grown from a cryopreserved specimen of this patient's marrow at relapse were normal, in contrast to haemopoietic colonies cultured from patients with chronic myelogenous leukaemia (CML) which contained the Ph1. A hypothesis which incorporates T-cell ALL with late development of the Ph1 into the overall family of Ph1 positive diseases is suggested.
We performed cytogenetic analysis of 11 normal-appearing granulocyte/macrophage colonies derived from cultures of the marrow of a child with acute myelomonocytic leukemia in relapse. We found diploid karyotypes and two abnormal ones--both hyperdiploid and containing the translocation t(1q-;11q+). A clonal origin of the karyotypic differences was suggested by the absence of variation within individual colonies. The evidence suggests that in this patient, the cytogenetic abnormality originated at or before the stage of granulocyte/macrophage progenitor.
Two male infants with almost complete trisomy 16q due to a maternal translocation, are reported. The phenotypic similarities of these patients who had trisomy 16q11 leads 16qter and of the eight previously published reports of partial trisomy 16q, were compared.
Four cases are described in which the drug mianserin was implicated in the development of leucopenia. In one case this was accompanied by fatal aplastic anaemia. In a second, generalized bone marrow depression occurred, although leucopenia was the only clinically significant manifestation. Mianserin may depress bone marrow function and haematological surveillance is appropriate for patients taking this drug.
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The outcome of pregnancy is reported for 23 women who had been drinking alcohol heavily and who were delivered in Belfast maternity hospitals during the last 4 years. Twenty-one (91%) of the babies were small-for-gestational age and many had head circumference measurements less than 5th centile. Ten babies (44%) had abnormal facies consistent with the 'fetal alcohol syndrome' and 10 babies had congenital malformations of the heart, palate, genitalia and kidneys. Perinatal problems which included breech presentation, birth asphyxia, hypoglycaemia, polycythaemia, hypocalcaemia and withdrawal symptoms were frequently present. Most of the babies have shown delayed postnatal growth and six of the ten who are aged over 1 year have delayed development.
The new perinatal death certificate proposed by the World Health Organisation was examined in relation to existing measures for recording perinatal death statistics and also with regard to new information gathered. Present procedures appear to underestimate the number of perinatal deaths by roughly 10%, though late registrations may lower this figure slightly. The use of a minimum birth weight as the criterion for inclusion in perinatal statistics removed much of the uncertainty associated with definitions of live birth and stillbirth. The new certificate led to duplication of some information already recorded through birth notification yet failed to provide information on some other factors generally considered relevant to perinatal mortality. The format proposed for recording cause of death provided a more logical presentation of events. Standardizing birth information recorded on all infants, modifying death certificates, and developing efficient record-linkage schemes would be more valuable than introducing the WHO certificate. Useful interpretation of the meaning of the characteristics of infants dying in the perinatal period awaits these timely changes.
Twenty-five infants with transient tachypnoea of the newborn (TTN) were examined by serial echocardiography during the first 4 days of life. The infants could be divided clinically into two groups: group 1 (n = 19) babies with mild classical TTN requiring less than 40% oxygen, and group 2 (n = 6) babies with severe TTN needing greater than 60% oxygen. Apart from amount of oxygen these two groups differed in that those with severe TTN had lower Apgar scores and arterial pH soon after birth. Echocardiography showed that the babies with classical TTN had increased left ventricular pre-ejection period to ejection times (LPEP/LVET) during the first day of life. Initial LPEP/LVET ratio correlated with duration of treatment with oxygen. The babies with severe TTN increased LPEP/LVET and right ventricular pre-ejection period to ejection times ratios (RPEP/ RVET) during the first 3 days of life. There was no correlation between systolic time intervals and duration of oxygen treatment. These findings suggest that there may be two distinct types of TTN: mild or classical type resulting from mild left ventricular failure, and a severe type associated with generalised myocardial failure, pulmonary hypertension, and right-to-left shunting.
As part of a wider survey of infections and defence mechanisms, concentrations of serum immunoglobulins IgG, IgA, and IgM were measured regularly by single radial immunodiffusion in a group of children receiving treatment for acute lymphoblastic leukaemia while in their first remission. IgM concentrations were often markedly raised at diagnosis, and IgG and IgA concentrations both began falling within one month of diagnosis. Four months after diagnosis all three had fallen significantly, but this tendency stopped after six months. Only IgG partially recovered, and non returned to pretreatment concentrations even in children followed for two years. The results suggest that vincristine and prednisone are the major factors that initiated the fall in IgG and IgA. Lowered IgM concentrations may have been due to cranial irradiation or continuous maintenance treatment, or both.