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Biomedical subjects

L Parker

Publications and source records attributed to L Parker.

At least 109 records · Page 6Linked to original sources
PubMed1997

Newborn screening for neuroblastoma.

Following favorable reports of infant screening for neuroblastoma, mass screening was introduced throughout Japan in 1985. Since then, reports from Japan, North America, and Europe have all confirmed that screening is associated with substantial overdiagnosis. Recent reports from both Japan and North America suggest that screening at under 1 year of age does not reduce the incidence of disease in older children or of advanced stage disease and is therefore likely to confer little survival advantage. Current screening studies in Europe are investigating the effects of screening in older children (10 to 14 months) in an attempt to reduce overdiagnosis. The effect of screening on mortality remains unknown. Mortality from neuroblastoma in Japan is falling, but most of the fall predates the possible effect of screening. Longer follow-up of the North American study and the recently implemented German study may eventually provide an answer.

Diagnostic Errors↗
PubMed1997

Audit of ascertainment of deaths to children born in Cumbria, UK, 1950-89 through the NHS central register.

STUDY OBJECTIVE: To evaluate the completeness of notification of deaths by the National Health Service Central Register (NHSCR) for England and Wales. DESIGN: Deaths for a birth cohort were ascertained through scanning the relevant volumes of NHSCR. Attempts were made to confirm these deaths and additional deaths were ascertained through searching local records. Logistic regression was used to investigate how the probability of a death being missed by NHSCR varied with the year of birth, age at death, sex, and social class. SETTING: Deaths up to the end of 1989 in the CA postal area among 264,046 children born between 1950 and 1989 to mothers living in Cumbria. RESULTS: NHSCR originally ascertained 4139 deaths; local searches confirmed 3338 (81%) of these and found an additional 342. Most deaths missed by the NHSCR were neonatal deaths in the 1950s and 1960s. In the 1950s, 31% of children who died in the neonatal period either were not entered on NHSCR or, if they were entered, there was no record of their death. For children born from 1970 onwards, ascertainment of deaths through NHSCR was over 99% complete. CONCLUSIONS: The NHSCR was started in 1948 for the administration of records of National Health Service patients. It seems that many babies who died soon after birth were not therefore recorded. In parallel with the increasing use of NHSCR for epidemiological purposes, there has been a substantial and continuing improvement in its clerical procedures since the mid 1960's.

Cause of Death↗
PubMed1997

Sex ratio in relation to fathers' occupations.

OBJECTIVE: To investigate whether the sex ratio of children varies between fathers of different occupations. METHODS: The sex ratio (the ratio of the number of boys to the number of girls at birth) was calculated in relation to paternal occupation in the cohort of all 253,433 live births in Cumbria, north west England, from 1950-89. Exact binomial confidence intervals were used to estimate whether the sex ratio in each occupational category was significantly different from that for the rest of the cohort. RESULTS: There were fewer occupational categories with significantly different sex ratios at the 5% level than expected by chance alone, assuming the same binomial distribution of sexes at birth within each paternal occupation. CONCLUSIONS: Significant variation of the sex ratio with fathers' occupations was not found. There is some evidence that the sex ratio shows less variance than expected under a binomial model which assumes independence of the sex of each child; a possible explanation of this may be parental preference for limiting family size after children of both sexes have been born or some other factor which results in children within a family being more likely to be of both sexes rather than the same sex.

Binomial Distribution↗
PubMed1996

In vitro biomechanical comparison of multistrand cables with conventional cervical stabilization.

STUDY DESIGN: The biomechanical stability of six different methods of cervical spine stabilization, three using multistrand cables, were evaluated in a bovine model. OBJECTIVES: To quantify and compare the in vitro biomechanical properties of multistrand cables used for posterior cervical wiring to standard cervical fixation techniques. SUMMARY OF BACKGROUND DATA: Fixation of the posterior cervical spine with monofilament stainless steel wire is a proven technique for stabilization of the cervical spine. Recently, multistrand braided cables have been used as a substitute for monofilament stainless steel wires. These cables, made of stainless steel, titanium, or polyethylene, are reported to be stronger, more flexible, and fatigue resistant than are monofilament wire based on mechanical testing. However, no in vitro biomechanical studies have been performed testing a standard posterior cervical wiring technique using multistrand cables. METHODS: Thirty-six fresh frozen cervical calf spines consistent in size and age were mounted and fixed rigidly to isolate the C4-C5 motion segment. Six different reconstruction techniques were evaluated for Rogers' posterior cervical wiring technique using: 1) 20-gauge stainless steel monofilament wire, 2) stainless steel cable, 3) titanium cable, 4) polyethylene cables, 5) anterior locking plate construct with interbody graft, and 6) posterior plate construct. Six cervical spines were included in each group (n = 6), with each specimen statically evaluated under three stability conditions: 1) intact, 2) reconstructed, and 3) postfatigue. The instability model created before the reconstruction consisted of a distractive flexion Stage 3 injury at C4-C5. Nondestructive static biomechanical testing, performed on an material testing machine (MTS 858 Bionix test system, Minneapolis, MN), included axial compression, axial rotation, flexion-extension, and lateral bending. After reconstruction and static analysis, the specimens were fatigued for 1500 cycles and then statically retested. Data analysis included normalization of the reconstructed and postfatigue data to the intact condition. The calculated static parameters included operative functional unit stiffness and range of motion. RESULTS: Posterior cervical reconstruction with stainless steel monofilament wire proved inadequate under fatigue testing. Two of the six specimens failed with fatigue, and this construct permitted the greatest degree of flexion-extension motion after fatigue in comparison with all other constructs (P < 0.05). There were no significant differences in flexural stiffness or range of motion between stainless steel, titanium, or polyethylene cable constructs before or after fatigue testing. The posterior cervical plate constructs were the stiffest constructs under flexion, extension, and lateral bending modes, before and after fatigue testing (P < 0.05). CONCLUSIONS: Multistrand cables were superior to monofilament wire with fatigue testing using an in vitro calf cervical spine model. There were no failures or detectable differences in elongation after fatigue testing between the stainless steel, titanium, and polyethylene cables, as shown by the flexion-extension range of motion. The posterior cervical plate construct offered the greatest stability compared with all other constructs.

Animals↗
PubMed1996

The pregnant ovine endometrium constitutively expresses and secretes a highly stable bombesin-like peptide, which shares C-terminal sequence but differs structurally from gastrin-releasing peptide.

Previous studies have shown that a peptide closely related to gastrin releasing peptide (GRP) is expressed by the pregnant ovine endometrium throughout gestation, however its molecular form and the mode of its secretion have not been defined. We have partially purified the endometrial GRP-like peptide and characterised it chromatographically. In contrast to other tissues, the main molecular form of endometrial GRP is larger (6-8 kDa versus 1-3 kDa), and based on the increased hydrophobicity of its circulating form after reduction, contains at least one disulfide bond. Reduction and treatment with chaotropic agents showed that the protein is not a cleavage product of pro-GRP bound to a binding protein. Tryptic cleavage demonstrated that the C-terminus of the peptide is closely related to GRP18-27 suggesting that bioactivity is likely. The partially purified peptide remained intact after incubation in ovine plasma for 16 h indicating that it is extremely stable and consistent with an hormonal role during pregnancy. Quantification of peptide from monolayer cultures of ovine endometrial cells showed that the GRP-like peptide was secreted constitutively. These data show that a stable, GRP-like peptide, distinct from the known processing products of pre-pro-GRP is constitutively expressed by the gravid ovine endometrium. Since endometrial GRP has an intact bioactive C-terminus and is mitogenic for numerous tissues including the uterus, then it is likely to play an important regulatory role in ovine pregnancy.

Amino Acid Sequence↗
PubMed1996

Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience.

Between 1989 and 1993, 255 tumor biopsies representing 4 tumor histologies (melanoma, breast cancer, colon cancer and renal cell cancer) were received by the Surgery Branch of the National Cancer Institute. Tumor-infiltrating lymphocytes (TIL) were grown from single-cell suspensions of tumor biopsies over the course of 30-45 days. The TIL were grown in medium containing IL-2. To obtain numbers suitable for therapy (>10(11)), TIL were expanded using a large-scale system of cell culture and harvesting. While the largest number of biopsies was obtained from melanoma patients, TIL were successfully grown from 160 of 255 tumor biopsies representing all 4 histologies. Under the culture conditions employed, several characteristics of TIL expansion were observed. The cell surface phenotype of TIL which grew out from the tumor biopsies was generally a mix of CD3+/CD4+ or CD3+/CD8+ lymphocytes. Only TIL from melanoma biopsies were found to be consistently cytolytic and, in many cases, lysed autologous tumor cells preferentially. Interestingly, TIL derived from extra-nodal sites of metastatic melanoma biopsies (subcutaneous, lung, bowel; 36 of 67, 54%) were more likely to have these cytolytic characteristics than TIL derived from tumor-involved lymph node biopsies (7 of 39, 18%). The present study summarizes 5 years of laboratory effort and validates the technologies developed for the large-scale growth and harvesting of TIL. In addition, it summarizes the laboratory effort supporting previously published clinical reports on TIL from our group.

Breast Neoplasms↗
PubMed1996

Radon and childhood cancers.

The effective radiation doses received by children living in high radon areas are similar to those which have been associated with an excess risk of malignant disease elsewhere. However, the only cancer known to be associated with radon is lung cancer--a disease which is not a condition of childhood. Thorne and his colleagues have conducted a study which could have demonstrated an excess of childhood malignancy only if the risk associated with radon was very high. The risk to health of high levels of radon in the environment remains uncertain. The United Kingdom Case Control Study of Childhood Cancers, under the chairmanship of Sir Richard Doll, is assessing risk from many factors including measured radon exposure and it is with great interest that we await the results.

Air Pollutants, Radioactive↗
PubMed1996

Screening for neuroblastoma in late infancy by use of EIA (enzyme-linked immunoassay) method: 115000 screened infants in Austria.

The aim of this study was to investigate the feasibility of a neuroblastoma screening programme for children in late infancy, based on collaboration of general paediatricians and practitioners in Austria, using the technique of enzyme-linked immunoassay (EIA) for biochemical analyses. Analysis of catecholamine metabolites in spot urine samples by EIA with high performance liquid chromatography as a backup was undertaken. Austrian infants (median age 8.7 months) were screened. Overall compliance was 30%. The EIA method had a high rate (6.7%) of false-positive results. 28 infants were admitted to hospital. In 15 cases, neuroblastoma was found (four stage 1, five stage 2B, six stage 3). The EIA method can be used for neuroblastoma screening, but requires a backup analytical technique in order to avoid unnecessary hospital admissions. The stage distribution and biological features of neuroblastomas diagnosed by screening at a later age are different from those detected by earlier screening. Screening in late infancy might be of more benefit than early screening.

Austria↗
PubMed1996

Leukaemia and non-Hodgkin's lymphoma in young persons resident in small areas of West Cumbria in relation to paternal preconceptional irradiation.

The results of a previous study suggested that an association between childhood leukaemia and the radiation dose received occupationally by a father before the conception of his child might provide the explanation for the marked excess of childhood leukaemia and non-Hodgkin's lymphoma in the village of Seascale, West Cumbria. The present study identifies other small areas (electoral wards) in West Cumbria where excess cases of leukaemia and non-Hodgkin's lymphoma in young people have occurred and determines whether a recorded dose of radiation was received occupationally by the father before the conception of each of the affected individuals. Forty-one cases of leukaemia and non-Hodgkin's lymphoma were diagnosed during 1968-85 in young people under 25 years of age resident in the 49 electoral wards lying within the boundary of West Cumbria and the adjacent ward of Broughton. Raised incidence rate ratios (two-sided P<0.01) were found for acute lymphoblastic leukaemia among those aged 0-14 years (concentrated among those aged 0-4 years) in Seascale ward and among those aged 0-24 years (also concentrated among those aged 0-4 years) in Egremont North ward, for acute myeloid leukaemia among those aged 0-14 years in Sandwith ward, for all leukaemias among those aged 0-14 years in Broughton ward (South Lakeland) and for non-Hodgkin's lymphoma among those aged 0-14 years in Seascale ward. For West Cumbria as a whole, incidence rates were not usual. Apart from Seascale, for none of these electoral wards has a father of an affected child been linked definitely to an occupational dose of radiation recorded before the conception of the child. Particularly striking are the excesses of acute lymphoblastic leukaemia cases among young children living in the wards of Seascale and Egremont North, situated 11 km apart. The cases in Egremont North are not associated with recorded doses of radiation received occupationally by fathers before the conception of the affected children, even though the total numbers of children associated with such doses born in Seascale and Egremont North wards are similar. This finding is further evidence against a causal role for paternal preconceptional radiation exposure in the cases of childhood leukaemia in Seascale.

Adolescent↗
PubMed1996

Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA.

Fanconi anaemia (FA) is an autosomal recessive disorder characterized by a diversity of clinical symptoms including skeletal abnormalities, progressive bone marrow failure and a marked predisposition to cancer. FA cells exhibit chromosomal instability and hyper-responsiveness to the clastogenic and cytotoxic effects of bifunctional alkylating (cross-linking) agents, such as diepoxybutane (DEB) and mitomycin C (MMC). Five complementation groups (A-E) have been distinguished on the basis of somatic cell hybridization experiments, with group FA-A accounting for over 65% of the cases analysed. A cDNA for the group C gene (FAC) was reported and localized to chromosome 9q22.3 (ref.8). Genetic map positions were recently reported for two more FA genes, FAA (16q24.3) and FAD (3p22-26). Here we report the isolation of a cDNA representing the FAA gene, following an expression cloning method similar to the one used to clone the FAC gene. The 5.5-kb cDNA has an open reading frame of 4,368 nucleotides. In contrast to the 63-kD cytosolic protein encoded by the FAC gene, the predicted FAA protein (M(r) 162, 752) contains two overlapping bipartite nuclear localization signals and a partial leucine zipper consensus, which are suggestive of a nuclear localization.

Amino Acid Sequence↗
PubMed1996

Comparison of the diagnostic and prognostic value of biological markers in neuroblastoma. Proposal for a common methodology of analysis. SENSE group.

BACKGROUND: The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. Screening programs have been initiated in infants of less than one year of age, based on the hypothesis that neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. However, recent analyses suggest that most cases discovered by screening are low stage tumors considered as dysembryogenetic residues devoid from major abnormalities and that high-grade tumors with molecular abnormalities are unrelated diseases. AIM OF THE REVIEW: To confirm one or the other hypothesis, and eventually identify biological factors possibly responsible for the initiation and progression of the disease, it is of utmost importance that all investigators agree on biological criteria for analysis when neuroblastoma tissue is available in screened and unscreened populations. This paper reviews the biological tools available for prognosis in neuroblastoma, the priority for analysis of biological markers according to both methodological reliability and feasibility, and the conditions of tissue storage for further analysis of these biological markers. CONCLUSION: The standardized biological evaluation of neuroblastoma will allow to collect sufficient data for multivariate analysis; such analysis is now fundamental if one wants to clearly define the respective impacts of biological abnormalities on neuroblastoma progression.

Biomarkers, Tumor↗