Biomedical subjects
Publications and source records attributed to A D Pearson.
Chromosomal abnormalities were detected in the bone marrow of a girl with disseminated retinoblastoma. One of these abnormalities, i(6p), is characteristic of primary retinoblastoma and its presence confirmed the diagnosis of bone marrow infiltration with retinoblastoma. This approach could be extended to study other tumours of childhood.
In a patient with stage IV disseminated neuroblastoma treated by chemotherapy extensive cytogenetic investigations were performed on the residual primary tumour and bone marrow immediately before myeloablative treatment and autologous marrow rescue. Two abnormal clones both showing lp+, a characteristic abnormality of neuroblastoma, were detected in cells from the residual primary tumour, providing direct evidence of persisting viable tumour. Such investigations should be a routine part of the assessment of response to treatment in patients with neuroblastoma, and could be extended to others in whom "second look" surgery is performed.
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Campylobacter pyloridis was isolated from 77% of 220 (35%) unselected adults undergoing gastroscopy. Isolation was significantly associated with histological gastritis (p less than 0.0001), duodenal ulcer (p less than 0.0001), and to a much lesser extent, with gastric ulcer (p less than 0.05). The relation between the isolation of C pyloridis and peptic ulcer seemed to be independent of coexisting gastritis. In those with no endoscopic or histological evidence of disease there was no relation between isolation and increasing age. Antibody responses to a whole cell sonicate of a strain of C pyloridis were measured by means of an enzyme linked immunosorbent assay (ELISA). Increased IgA (p less than 0.0001) and IgG (p less than 0.0001) antibody titres were found in patients with C pyloridis. Peptic ulceration or gastritis were present in 78% and 100% of patients with a high concentration of IgG and IgA, respectively, but in only 9% and 18% of those with low titres. These results provide further evidence for a possible pathogenic role of these organisms in gastric disease and suggest that immunological markers of their presence might be useful non-invasive indicators of disease.
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Fatal fungal pneumonias developed in two children with ALL during remission induction. Pulmonary and central nervous system signs suggested the L-asparaginase-induced multiple-thromboses syndrome in both children. Fungal infection should be considered-whenever pneumonia develops in a neutropenic child already receiving broad-spectrum antibiotics or when multiple thromboses occur.
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Serum methotrexate concentrations have been measured in 28 children with acute lymphoblastic leukaemia (ALL) following PO administration under standard conditions. Small-intestinal transit time, measured by the time taken for lactulose to pass from mouth to caecum, has been related with methotrexate absorption parameters. Small intestinal transit times ranged from 30 to 240 min. Children with longer transit times had later times of peak methotrexate concentration and tended to have a more erratic methotrexate absorption profile with two peaks. There appears to be an optimal transit time between 90 and 105 min for methotrexate absorption, with both faster and slower small-intestinal transit times producing lower peak concentrations as a fraction of the dose.
The virulence of Campylobacter jejuni and C. coli isolated from various water sources was compared with that of clinical strains by in vitro assays of adhesion, invasion and cytotoxicity to HeLa cells. Variation in degree of attachment was observed, but this did not appear to be related to strain source, However, water strains were less invasive and less cytotoxic to HeLa cells than clinical strains as shown by immunofluorescence and electron microscopy. These differences were particularly evident between clinical and water isolates of the same serotype and biotype implicated in an outbreak of campylobacter enteritis in a school. The enhanced virulence of the clinical isolates, possibly induced by passage, was confirmed by colonization tests on infant mice.
Outer membrane proteins of Campylobacter jejuni and other campylobacter species were analyzed for their antigenic potentials by immunoblotting. Polypeptides were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred electrophoretically, and reacted with rabbit antisera to C. jejuni. Each Campylobacter species analyzed demonstrated a unique outer membrane protein antigenic profile; interspecies antigen sharing was observed to be compatible with the degree of DNA relatedness between the species. The most highly conserved outer membrane protein antigen was the flagellum (molecular weight, 62,000). An aflagellate mutant was found to be untypable with the heat-labile system, in contrast to its parental isolate. The immunogenic potentials of C. jejuni proteins were examined by immunoblot analysis of sera from infected humans. Sera of convalescent patients, reacted with their homologous C. jejuni isolates, recognized a variety of campylobacter proteins. The most consistent immunogen in human infection was the flagellar protein. Patient sera assayed by the immunoblot technique were easily distinguished from control sera, which did not recognize specific campylobacter antigens. These findings suggest that the campylobacter flagellar protein is an essential determinant of the heat-labile antigen typing scheme and is the dominant immunogen recognized during C. jejuni infections in humans.
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The outer membrane proteins of five clinical isolates of Campylobacter jejuni were identified by 125I-surface labelling and SDS-PAGE of outer membrane preparations. All isolates expressed a major outer membrane protein of variable molecular weight (43 000-46 000: 43K-46K). Several constant surface proteins were also identified including a 27K protein which was surface-exposed and acid-extractable but was not present in the outer membrane preparations. Isolated flagella comprised a major 62K protein and a minor 87K protein. Both proteins were absent in an aflagellate variant. The 62K protein was immunoblotted and immunoprecipitated by rabbit anti-flagella antisera.
Fifty Campylobacter jejuni isolates, including 29 from humans associated with an outbreak of enteritis, 20 from cattle, and 1 from a milk source, were serotyped on the basis of extractable thermostable antigens and examined by bacterial chromosomal restriction endonuclease digest analysis. Serotyping showed specific differences between the human isolates and the milk isolates, but each of these generally, although not consistently, reacted with 4 of the 42 C. jejuni typing antisera. Restriction patterns of all of the human isolates and some of the cattle isolates were indistinguishable, confirming the suspected link between the cattle and the human outbreak. The single milk isolate had a restriction pattern unlike those of the human isolates, and therefore its involvement in the transmission of infection from the cattle to the humans could not be confirmed.
Small bowel function before, during, and after treatment for acute lymphoblastic leukaemia was studied in 26 children. A significant impairment of D-xylose absorption was found during treatment. Permeability studies showed a significant decrease in mannitol and a significant increase in lactulose concentrations; five of 20 children tested had evidence of lactose malabsorption, three of whom were symptomatic. Intestinal function abnormalities were greater in children whose methotrexate treatments were separated by 7 day than by 16 day intervals. Only five (19%) children had no abnormal tests. Abnormalities of small bowel function may be treatment induced and this has implications for morbidity from gastrointestinal symptoms, impairment of the mucosal barrier, and malabsorption of both nutrients and drugs leading to malnutrition and suboptimal drug concentrations.
A child is described who, following surgery and irradiation for malignant choroid plexus papilloma at the age of 11 months, developed three further tumors: A benign myxofibroma of the cranium at the age of 3 1/2 years, an undifferentiated anaplastic tumor of his clavicle at 7 1/2 years, and a chondroblastic osteogenic sarcoma of his pelvis at the age of 12 years. There was no apparent genetic predispositions to malignancy. The latter three neoplasms may have originated either in, or at the edge of, the original radiotherapy field, suggesting that the child has a particular susceptibility to the oncogenic potential of radiotherapy.
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An outbreak of gastroenteritis affecting 234 pupils and 23 staff at a boarding school occurred over a period of 8 weeks. Campylobacter spp. were isolated from pupils and staff, and from two samples of cold water taken from an open-topped storage tank which supplied predominantly unchlorinated water to the main school building. The two isolates from water were of the same serotype. This serotype was the commonest of the three serotypes of Campylobacter jejuni detected in isolates from pupils and staff. There was a highly significant association between consumption of water from the cold water storage tank and reported illness in staff. Attack rates in pupils corresponded closely with the extent of distribution of this water-supply to the main residential houses. Contamination of water by faecal material from birds or bats was the most likely source of infection.