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Biomedical subjects

N Wald

Publications and source records attributed to N Wald.

At least 19 recordsLinked to original sources

Deterministic effects from occupational radiation exposures in a cohort of Mayak PA workers: data base description.

Project 2.3 of the Joint Coordinating Committee on Radiation Effects Research (JCCRER) is a study of deterministic health effects among a cohort of Russia nuclear workers. The preliminary study population includes a stratified random sample of 221 radiation workers who were employed in a cohort of 8,055 workers at the Mayak PA facilities for at least one year during the period from 1948 to 1958. High annual doses, approaching 1 Gy per year from external and internal radiation sources, were reported for a significant proportion of the workers in this cohort. The present data set includes 96 cases of chronic radiation sickness (CRS), 14 cases of acute radiation syndrome (ARS) and 13 cases of plutonium pneumosclerosis (PPn). The remainder of the sample consists of "uninjured workers" who had no known history of radiation illness or injury; however, the uninjured workers are not "controls" for radiation exposure. The data base is currently being expanded to 600 individuals sampled from the cohort of workers from 1948 to 1958 to allow a more complete analysis of the deterministic health effects and comparisons with existing health effect models. The final data base will be used with state-of-the-art modeling techniques to determine threshold doses and dose-response relationships for key clinical diagnostic variables.

Acute Disease↗

Activation of the nitric oxide synthase 2 pathway in the response of bone marrow stromal cells to high doses of ionizing radiation.

Reverse transcription-polymerase chain reaction and immunofluorescence analysis of D2XRII murine bone marrow stromal cells showed that gamma irradiation with doses of 2-50 Gy from (137)Cs stimulated expression of nitric oxide synthase 2 (Nos2, also known as iNos). The activation of Nos2 was accompanied by an increase in the fluorescence of 4,5-diaminofluorescein diacetate, a nitric oxide trap, and accumulation of 3-nitrotyrosine within cellular proteins in a dose-dependent manner. These effects were inhibited by actinomycin D and by N-[3-(aminomethyl)benzyl]acetamidine dihydrochloride, a specific inhibitor of Nos2. The induction of Nos2 expression and Nos2-dependent release of nitric oxide in D2XRII cells was observed within 24 h after irradiation and was similar in magnitude to that observed in cultures incubated with Il1b and Tnf. We conducted (1) confocal fluorescence imaging of 3-nitrotyrosine in bone marrow cells of irradiated C57BL/6J mice and (2) 3-nitrotyrosine fluorescence imaging of FDC-P1JL26 hematopoietic cells that were cocultured with previously irradiated D2XRII bone marrow stromal cells. Exposure to ionizing radiation increased the production of 3-nitrotyrosine in irradiated bone marrow cells in vivo and in nonirradiated FDC-P1JL26 cells cocultured with irradiated D2XRII cells for 1 or 4 h. We suggest that nitrative/oxidative stress to the transplanted multilineage hematopoietic cells due to exposure to nitric oxide released by host bone marrow stromal cells may contribute to the genotoxic events associated with malignant alterations in bone marrow tissue of transplant recipients who are prepared for engraftment by total-body irradiation.

Animals↗

Routine ultrasound scanning for congenital abnormalities.

Screening has been defined as "the systematic application or a test or enquiry, to identify individuals at sufficient risk of a specific disorder to benefit from further investigation or direct preventive action, among persons who have not sought medical attention on account of symptoms of that disorder" (Wald, N.J. 1994. J. Med. Screen. 1:76). The purpose of screening is to benefit the individuals being screened. The early detection of abnormalities should not be an end in itself, and the value of a screening approach needs to be determined before it is introduced into practice. Ultrasound as a means of screening for fetal abnormalities has not been adequately assessed even though it is widely used in this way. To assess its value it is helpful to classify abnormalities that can be detected on the basis of the clinical usefulness of doing so. To this end we propose four categories similar to those independently suggested by the Royal College of Obstetricians and Gynaecologists Working Party on Ultrasound Screening for Fetal Abnormalities. Four groups were specified: (A) major abnormalities--death inevitable, (B) abnormalities associated with long-term handicap, (C) abnormalities potentially amenable to intrauterine treatment, and (D) fetal conditions that require immediate postnatal investigation and/or treatment. For each abnormality, the screening detection and false-positives need to be estimated together with the medical and financial costs of screening, particularly those arising from findings of uncertain or little medical consequence that may lead to worry and further unnecessary obstetric intervention.

Congenital Abnormalities↗

A near-haploid bone marrow karyotype in systemic mast cell disease: is it characteristic of the disease or an incidental finding?

We present the case of a 40-year-old man with aggressive systemic mast cell disease. The patient had a predominant near-haploid clone in his bone marrow cells, detected by cytogenetic analysis performed at the time of diagnosis. The similarities between this case and a previously published case of near-haploidy in a patient with malignant mastocytosis suggest that near-haploidy may be a characteristic of aggressive systemic mast cell disease rather than an incidental finding.

Adult↗

The distribution of nuchal translucency at 10-13 weeks of pregnancy.

There is a need for a simple method of expressing nuchal translucency measurement in early pregnancy that will allow for gestational age and be useful in screening for Down's syndrome. To achieve this objective, we conducted a prospective study of 561 women with singleton pregnancies that were not affected by Down's syndrome at 10-13 weeks of gestation. Nuchal translucency measurements and crown rump length measurements were determined. Nuchal translucency measurement increased by about 17 per cent per week. Expressing the result as a multiple of the median (MOM) nuchal translucency for a given crown rump length allowed for this increase with gestational age and yielded a distribution of values that was approximately Gaussian. About 96 per cent of values lay between 0.5 and 2.0 MOM. The variance and therefore the false-positive rate of nuchal translucency were significantly reduced by recording several measurements and using the average: for example, the false-positive rate reduced from 8.3 per cent to 5.0 per cent if the average of six measurements were used instead of one--a potential 40 per cent reduction in the false-positive rate if the test were used in screening. Estimating the distribution of nuchal translucency in MOM values will assist in specifying the statistical parameters to be used in prenatal screening for Down's syndrome and the use of repeated nuchal translucency measurements is expected to have a useful effect on reducing the screening false-positive rate at a given MOM cut-off level.

Adult↗

Acquired monosomy 7 in donor cells in a patient treated for acute lymphoblastic leukemia with bone marrow transplantation.

Two years after a bone marrow transplant (BMT) from his haploidentical mother, a 28-year-old male with a history of acute lymphoblastic leukemia (ALI.) developed myelodysplastic syndrome (MDS) with monosomy 7 in his female bone marrow cells. Follow-up cytogenetic studies, including fluorescence in situ hybridization (FISH) performed twenty-seven and thirty-one months post-BMT consistently showed a female chromosome pattern with monosomy 7. Thirty-six and thirty-nine months post-BMT, further clonal evolution occurred, with the appearance of a sideline of the female cells that first expressed a del(10)(p11.2) and then developed a translocation, t(10;21)(p11.2;q22), in addition to the monosomy 7. Cytogenetic monitoring of this male patient helped to reveal a rare case of early MDS in transplanted donor cells and evolution of the acquired abnormal clone by identifying chromosomal alterations in the donated female bone marrow cells.

Adult↗