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Biomedical subjects

J R Mann

Publications and source records attributed to J R Mann.

At least 109 records · Page 6Linked to original sources

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): past medical history in children with cancer.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) collected interview and medical information relating to the child's past medical experiences from parents of 555 children diagnosed with cancer and parents of 1110 unaffected matched controls. No significant associations emerged overall for ante-natal care, place and mode of delivery, length of gestation, birth weight, condition at birth, special care, neonatal procedures or breast-feeding. Few risk factors relating to previous illnesses and medication were found, although increasing numbers of illnesses appeared to be associated with an increased risk of childhood cancer, particularly acute lymphoblastic leukaemia. A highly significant excess of case children had not been immunised (p = 0.005). In general, these results indicate that past medical experiences have little influence on the development of cancer in children.

Adolescent↗

Neuroblastoma--when are urinary catecholamines and their metabolites 'normal'?

The overproduction of catecholamines and their metabolites is a well recognised feature of neuroblastoma. Published data are scarce for their urinary excretion in children with neuroblastoma and in ill children in whom this diagnosis may be considered. We have determined a graphical upper reference limit for total catecholamines, total metadrenalines and HMMA in urine, expressed as a ratio to the creatinine concentration, for a group of 174 children with neuroblastoma and 704 hospitalised children with other disorders. This graph has been determined by examining the overlap region between the results for the two groups of children and avoids the irregularities caused by statistical outliers. The sensitivity and specificity of the individual tests indicate that total catecholamines is marginally the best single test to perform when trying to diagnose neuroblastoma, with the best clinical sensitivity being achieved by examining both total catecholamines and HMMA. Only two of the 174 children with neuroblastoma would not have been detected using these two tests. Total metadrenalines did not appear to add any further information and could be dropped from the repertoire in favour of the other two measurements.

Adolescent↗

Two maternally derived X chromosomes contribute to parthenogenetic inviability.

In certain extraembryonic tissues of normal female mouse conceptuses, X-chromosome-dosage compensation is achieved by preferential inactivation of the paternally derived X. Diploid parthenogenones have two maternally derived X chromosomes, hence this mechanism cannot operate. To examine whether this contributes to the inviability of parthenogenones, XO and XX parthenogenetic eggs were constructed by pronuclear transplantation and their development assessed after transfer to pseudopregnant recipients. In one series of experiments, the frequency of postimplantation development of XO parthenogenones was much higher than that of their XX counterparts. This result is consistent with the possibility that two maternally derived X chromosomes can contribute to parthenogenetic inviability at or very soon after implantation. However, both XO and XX parthenogenones showed similar developmental abnormalities at the postimplantation stage, demonstrating that parthenogenetic inviability is ultimately determined by the possession of two sets of maternally derived autosomes.

Animals↗

Urinary catecholamines and their metabolites in management of neuroblastoma.

Measurements of urinary total catecholamines expressed as dopamine (TC) and their metabolites, total metadrenalines (TM) and 3-methoxy-4-hydroxy mandelic acid (HMMA) were made on 24-h urine collections from 56 previously untreated children with neuroblastoma. All results were expressed as a ratio to the creatinine excretion and were compared with "smoothed" age-related reference ranges derived from results in 704 children with other illnesses. Urinary catecholamines/metabolites excretion was elevated in 55 of the 56 patients, the exception being a baby with opsomyoclonus. TC was raised in 47, HMMA in 41, and TM in 37. Eleven patients had elevations of one parameter (TC in 10, HMMA in 1), 15 had 2 elevated levels, and 29 had elevations of all three. The TM level was the least contributory, as in no patient was it the only parameter elevated. Serial measurements were performed in 40 children, and the results correlated closely with the clinical progress of the disease and in some children permitted early detection of recurrence.

Catecholamines↗

Malignant peritoneal mesothelioma in childhood.

We present a case of diffuse malignant peritoneal mesothelioma, initially misdiagnosed as benign. Electron microscopy and immunocytochemistry proved helpful diagnostically. Using monoclonal antibodies against cytokeratin and vimentin, we compared neoplastic with normal and reactive mesothelia and we found coexpression of these two intermediate filaments in the reactive and neoplastic mesothelial but not in the normal mesothelia, supporting the suggestion that surface mesothelial cells are derived from multipotential submesothelial cells.

Adolescent↗

Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens.

Eight children treated between 1977 and 1983 with the UK Children's Cancer Study Group's non-Hodgkin lymphoma (NHL) and T-cell protocols have developed second malignancies within 7 years of commencing treatment. Five developed acute non-lymphoblastic leukaemia and a sixth died from infection while pancytopenic with a pre-leukaemic marrow. The other malignancies were cerebral astrocytoma and an undifferentiated low grade sarcoma. These eight children were included among 261 children studied in the first UKCCSG NHL and T-cell trials giving an actuarial incidence of 7.8% second malignancy at 7 years. Six had received adjuvant radiotherapy which may have contributed to the high incidence of second malignancy.

Adolescent↗

The inter-regional epidemiological study of childhood cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma.

The inter-regional epidemiological study of childhood cancer analysed data on 234 children diagnosed with leukaemia or lymphoma and 468 controls matched for age and sex. A wide range of potential risk factors was examined, including prenatal exposure to x rays, maternal drug ingestion and smoking, child's medical history, and parental medical conditions and occupation. Calculations were completed for leukaemia or lymphoma and diagnostic subgroups, as defined by laboratory confirmed cell type. In utero exposure to narcotic analgesics was weakly associated with leukaemia or lymphoma but no other antenatal factors gave significant risks. New associations were identified for skin diseases in both parents and congenital abnormalities in the mothers of children with leukaemia. For past medical conditions in the child, viral disease occurring under 6 months of age increased the risk for acute lymphoblastic leukaemia. Fewer children in the leukaemia or lymphoma group had been immunised compared with the control groups. Case children diagnosed over the age of 9 years were more likely than controls to have had four or more previous episodes of illness. Overall, these results indicate that prenatal factors may be less important than postnatal or genetic influences in the development of leukaemia or lymphoma in children.

Adolescent↗

The development of XO gynogenetic mouse embryos.

Diploid gynogenetic embryos, which have two sets of maternal and no paternal chromosomes, die at or soon after implantation. Since normal female embryos preferentially inactivate the paternally derived X chromosome in certain extraembryonic membranes, the inviability of diploid gynogenetic embryos might be due to difficulties in achieving an equivalent inactivation of one of their two maternally derived X chromosomes. In order to investigate this possibility, we constructed XO gynogenetic embryos by nuclear transplantation at the 1-cell stage. These XO gynogenones showed the same mortality around the time of implantation as did their XX gynogenetic counterparts. This shows that the lack of a paternally derived autosome set is sufficient to cause gynogenetic inviability at this stage. Autosomal imprinting and its possible relation to X-chromosome imprinting is discussed.

Animals↗

The Inter-Regional, Epidemiological Study of Childhood Cancer (IRESCC): case-control study in children with germ cell tumours.

In 1980-1983 members of IRESCC interviewed parents of 555 children with newly diagnosed cancer on topics of possible aetiological significance. Identical questions were asked of the parents of 1100 control children chosen from hospital admissions and general practitioner lists. Medical information was confirmed whenever possible by cross-checking with NHS records. Data for the 41 children with germ cell tumours and their 82 controls are reported here. The cases had more major congenital malformations than controls, including one neural tube defect. More case than control mothers and fathers reported occupational exposure to chemicals. Nine close relatives of cases had multiple primary tumours, which were often benign or of low-grade malignancy, compared with 1 hospital control and 3 general practitioner control relatives. Cases and controls differed with respect to birth weight and paternal age. No case-control differences were shown for: birth rank, maternal age, chronic illnesses and smoking, mothers' reproductive histories and oral contraceptive usage. In index pregnancies there were no case-control differences for maternal illness, infections, alcohol intake and X-ray and ultrasound exposure. There was no difference between cases and controls for the frequency of twinning the families.

Adolescent↗

Carney's triad: gastric leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma in young females.

The case of a 13-year-old girl with a gastric leiomyosarcoma and a pulmonary osteochondroma is presented. The association of these two tumours and extra-adrenal paraganglioma has been described as a triad by Carney. The patient is free of recurrence of the gastric tumour with no evidence of paraganglioma 10 months after the operation. To our knowledge this is the first case of the triad reported in the UK.

Adolescent↗

DDK egg-foreign sperm incompatibility in mice is not between the pronuclei.

A high rate of normal postimplantation development was achieved when the pronuclei of embryos from matings of DDK females with (CBA X C57BL/6J)F1 males were transplanted into enucleated embryos of non-DDK origin. This shows that the DDK egg cytoplasm, not the maternal pronucleus, is involved in the late preimplantation-lethal incompatibility.

Animals↗

Serum copper, serum ceruloplasmin, and erythrocyte sedimentation rate measurements in children with Hodgkin's disease, non-Hodgkin's lymphoma, and nonmalignant lymphadenopathy.

Between 1975 and 1981, 29 children with Hodgkin's disease, 22 with non-Hodgkin's lymphoma, and 13 with lymphadenopathy from various nonmalignant causes were studied with respect to the usefulness of serum copper, ceruloplasmin, and erythrocyte sedimentation rate (ESR) as markers of disease activity. Although elevated copper and ceruloplasmin levels were indicators of disease activity in the childhood lymphomas, and in patients with Hodgkin's disease the levels tended to be higher in those with advanced clinical stage, they were no better markers of disease activity than the ESR. Moreover, elevated serum copper and ceruloplasmin were nonspecific, since one child with benign lymphadenopathy and one Hodgkin's disease patient with an infection had raised levels. Low levels of copper and ceruloplasmin were found in four jaundiced patients probably because of impaired hepatic synthesis of ceruloplasmin. The authors conclude that serum copper and ceruloplasmin levels are no better markers of disease activity in children with lymphomas than is the ESR.

Adolescent↗

Adreno-cortical carcinoma in infancy and childhood: a radiological report of ten cases.

Adreno-cortical carcinoma is a relatively rare neoplasm in infancy and childhood. This review, covering a period of 18 years (1965-83), revealed 10 cases, the study being prompted by three patients in whom the final diagnosis was considerably delayed. There were eight females and two males and their ages ranged from 6 months to 14 years; 50% were below the age of 18 months at the time of the presentation. Seven patients had features of either virilism or precocious puberty and three of these also had stigmas of Cushing's syndrome. In patients where the endocrine disturbance was evident, the clinical diagnosis was made rapidly. However, delay in diagnosis occurred when endocrinopathy was absent. Radiology, including newer methods of imaging, contributed by revealing the tumour and its spread but did not suggest a conclusive diagnosis. At times, clinical features, biochemical findings, radiological investigations and even histological studies mislead, thus delaying the final diagnosis. These cases are illustrated and discussed.

Adolescent↗

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCO). Study design, control selection and data collection.

The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC) was established to investigate the role of possible aetiological factors in childhood cancer, with particular emphasis on environmental exposures to the foetus and family history of certain diseases including cancer. Incident cases occurring in three Health Service regions (the West Midlands, Yorkshire and North Western) were matched for age and sex with two sets of control children. A total of 555 cases and 1110 controls were entered into the study. The parents of each index child were interviewed with respect to events during the relevant pregnancy, occupation, smoking habits, and past medical history of themselves, the child's siblings and other relatives. Ninety-three per cent of case parents approached agreed to be interviewed, and approximately 90% of controls were ranked first or second on the control selection lists. After the interview information was verified by reference to antenatal and other medical records. Obstetric and general practitioner records were abstracted for approximately 90% of cases and controls. Information derived from the interview and that from medical records was coded separately. The data collected by each region have been pooled and case-control comparisons of potential aetiological factors will be carried out, using matched triplet analyses.

Adolescent↗

Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC): childhood cancer and the consumption of debendox and related drugs in pregnancy.

Attention has recently focused on the possible teratogenic effects of the combination antiemetic doxylamine succinate, dicyclomine hydrochloride and pyridoxine hydrochloride (Debendox/Bendectin) prescribed to pregnant women. The Inter-Regional Epidemiological Study of Childhood Cancer (IRESCC), a case-control investigation has analysed data derived from interview reports and medical records of 555 mothers of children (under 15 years) with cancer and 1110 mothers of matched control children. Separate analyses of interview reports and medical records both suggested that antiemetic ingestion during the index pregnancy does not increase the risk of developing childhood malignant disease in the exposed foetus. No dose-response relationship was evident. The lack of any significant relative risks held good for diagnostic sub-groups and when the trimester of ingestion was considered. Our results suggest that antimetics of this type are unlikely to be transplacental carcinogens.

Adolescent↗

Formaldehyde: a comparative evaluation of four monitoring methods.

The performances of four formaldehyde monitoring devices were compared in a series of laboratory and field experiments. The devices evaluated included the DuPont C-60 formaldehyde badge, the SKC impregnated charcoal tube, an impinger/polarographic method and the MDA Lion formaldemeter. The major evaluation parameters included: concentration range, effects of humidity, sample storage, air velocity, accuracy, precision, interferences from methanol, styrene, 1,3-butadiene, sulfur dioxide and dimethylamine. Based on favorable performances in the laboratory and field, each device was useful for monitoring formaldehyde in the industrial work environment; however, these devices were not evaluated for residential exposure assessment. The impinger/polarographic method had a sensitivity of 0.06 ppm, based on a 20-liter air sample volume, and accurately determined the short-term excursion limit (STEL). It was useful for area monitoring but was not very practical for time-weighted average (TWA) personal monitoring measurements. The DuPont badge had a sensitivity of 2.8 ppm-hr and accurately and simply determined TWA exposures. It was not sensitive enough to measure STEL exposures, however, and positive interferences resulted if 1,3-butadiene was present. The SKC impregnated charcoal tube measured both TWA and STEL concentrations and had a sensitivity of 0.06 ppm based on a 25-liter air sample volume. Lightweight and simple to use, the MDA Lion formaldemeter had a sensitivity of 0.2 ppm. It had the advantage of giving an instantaneous reading in the field; however, it must be used with caution because it responded to many interferences. The method of choice depended on the type of sampling required, field conditions encountered during sampling and an understanding of the limitations of each monitoring device.

Air Pollutants, Occupational↗