Biomedical subjects
Publications and source records attributed to W Walker.
The clinical course and necropsy findings are described of an 11-year-old child found to have active cytomegalovirus infection at the time of bone marrow transplantation for acute lymphoblastic leukaemia. Attention is drawn to the presence of primitive mononuclear cells of uncertain origin in the regenerating bone marrow.
Seventeen adult patients with previously untreated acute lymphoblastic leukaemia (ALL) were entered into a schedule of chemotherapy in which 3 combinations, each of 4 drugs, were administered in a predetermined cyclical rotation in combination with cranial irradiation and intrathecal injections of methotrexate. Of the 17 patients, 16 completed induction therapy and 15 (94%) entered remission. The only patient with T-ALL died before receiving any therapy. The median survival for all patients (17) was 22 months. Meningeal leukaemia did not occur during the haematological remission phase although 3 patients developed this complication following relapse. The authors conclude that the addition of cyclophosphamide and cytosine arabinoside to vincristine/prednisone provides excellent remission induction but the aggressive maintenance schedule employed has not led to significant long-term survival.
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A controlled, prospective study comparing streptokinase and heparin treatment has been completed in 51 patients presenting with acute proximal venous thrombosis of less than 8 days' clinical duration. Patients were studied by means of pre-treatment, post-treatment, 3- and 12-monthly phlebography and pulmonary perfusion scanning and were followed up at 3-monthly intervals. Of the 26 patients randomized to receive streptokinase, therapy was stopped in 3 because of complications. Phlebography 5 days after starting treatment showed 80--100 per cent lysis in 17 of the 23 patients who completed the course of streptokinase. Two patients later developed partial rethrombosis. One patient developed an asymptomatic pulmonary embolus during treatment. During follow-up (mean 19 months) only 1 of the 17 patients with 80--100 per cent lysis developed postphlebitic symptoms, 3 patients died of unrelated causes and 1 patient was lost to follow-up. In patients randomized to heparin therapy no significant lysis was achieved in any of the 25 patients and only 2 of these patients were found to have asymptomatic legs on follow-up. Two patients in this group died and autopsy confirmed massive pulmonary embolus during treatment. These data suggest that streptokinase is superior to heparin in the treatment of acute proximal venous thrombosis of less than 1 week's clinical duration especially if the thrombus is largely non-occlusive. It must be stressed that in order to avoid the bleeding complications of thrombolytic therapy, streptokinase must not be used within 10 days of major surgery, or even longer after vascular, neurosurgical or eye operations.
The pattern of virus isolation and illness was studied in 64 children with acute lymphoblastic leukaemia (ALL) during periods of apparent infection and when the children were well. The virus isolation rate of 2.2 viruses per child a year is similar to that previously found in normal children. In only 32% of children with symptoms were viruses found and 14.5% had viruses isolated when asymptomatic. The children with ALL appear to be more vulnerable to multiple virus infections and to excrete the virus for longer periods. This may be due to failure of production of both local and systemic antibodies. The failure in the past to recognise the true importance of virus infections in ALL may have been due to inadequate diagnostic techniques.
The diverse spectrum of acquired chromosome abnormalities in a female patient with myelofibrosis and myeloid metaplasia is described. A sequence of karyotypic evolution involving a ring chromosome is postulated. The terminal clinical picture was unusual in that there was obstructive renal failure from extramedullary myeloblastic transformation and infiltration of the bladder, and this was also present in other sites. Initially neutrophils showed low alkaline phosphatases activity but latterly two distinct populations in which cells had either high activity or none.
In the 27 years, 1951--1977, 4315 babies weighing over 1 kg were born alive in Newcastle suffering from haemolytic disease of the newborn due to Rhesus isoimmunization; 197 (4.5 per cent) died within four weeks of delivery. Many babies with severe anaemia (cord Hb less than or equal to 8 g/dl) died of cerebral and/or pulmonary haemorrhage as a result of coagulation failure; others with hydrops had a chance of recovery with intensive care as long as there was no associated pulmonary hypoplasia. Hyaline membrane disease was no more common in babies with haemolytic disease than in other preterm babies of comparable birthweight, but incorrect assessment of gestational age prior to the induction of labour increased the risk of death from hyaline membrane disease. The introduction of closed chest cardiac massage virtually eliminated the risk of sudden unexpected death during exchange transfusion but there was still a 1.5 per cent chance of sudden circulatory collapse during exchange transfusion. Affected babies of less than 36 weeks gestation with respiratory problems face a substantial risk of kernicterus when the indirect serum bilirubin level exceeds 270 mumol/l (15 mg/100 ml). The establishment of a single referral centre for Rhesus isoimmunization reduced neonatal mortality in the area to half the national average in the early 1950's and this superiority was maintained throughout the next decade.
Nesting success of ospreys (Pandion haliaetus) breeding in the Connecticut--Long Island area has increased since 1973 and is now approaching the levels recorded prior to the 1950's. Simultaneously, DDE and dieldrin residues have declined in unhatched eggs. Levels of polychorinated biphenyls have shown no changes over the period 1969 to 1976. The increase in productivity is attributed primarily to lower levels of DDE contamination. Detrimental effects in the past on ospreys in the Connecticut River estuary are attributed to local contamination with dieldrin.
In 4 women lymphomas developed 2 months to 12 years after the onset of systemic lupus erythematosus. An association between the two diseases had previously been reported in 14 cases, in 6 of which the lymphoma either preceded or was diagnosed at the same time as the autoimmune disease. In systemic lupus erythematous early biopsy of suspect lymph-nodes is recommended.
Clinical and haematological details of 2 siblings with a familial myeloproliferative disorder (erythroleukaemia) are presented. Their father is presumed to have died from a similar disease. The 2 siblings showed similar but not identical chromosomal abnormalities detected initially in marrow and later in peripheral blood. Serial studies revealed the emergence of an increasingly diverse pattern of chromosomal changes coincident with the haematological and clinical progression of the disease. Other members of the family were screened for cytogenetic and haematological changes. The paternal sibship displayed an increased incidence of cancer.
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The effects on neutrophil count and complement activity of five different haemodialysis membranes were studied. There was no correlation between the degree of neutropenia and intensity of complement activation. With cuprophan membrane both occurred simultaneously but to unrelated degrees; polyacronitrile induced mild, not significant neutropenia but marked activation of complement; polycarbonate membranes induced severe neutropenia without detectable complement activation. Where complement activation occurred it was via the alternative pathway. Haemodialysis induced neutropenia may have many causes and complement activation is probably not the major responsible factor.
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