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Biomedical subjects

N Wald

Publications and source records attributed to N Wald.

At least 19 recordsLinked to original sources
PubMed2005

Current concepts in screening for noncommunicable disease: World Health Organization Consultation Group Report on methodology of noncommunicable disease screening.

Screening people for serious diseases is receiving increasing attention as studies demonstrates the potential benefits of early detection and early intervention in preventing morbidity and mortality. Screening tests are available for some of the most important noncommunicable diseases, including cardiovascular disease, type 2 diabetes and several site-specific cancers. However, screening guidelines for cardiovascular disease, cancers and diabetes vary within and between countries because many national and international organizations are developing their own guidelines. There is a need to address the issue of screening for disease, with an emphasis on providing accurate and practical information relevant to all countries. This report arose from a Consultation Group meeting held at WHO headquarters in Geneva. It presents an examination of the principles of screening with an emphasis on noncommunicable disease prevention and control policy.

Humans↗
PubMed2003

Salt conditions a flavor preference or aversion after exercise depending on NaCl dose and sweat loss.

Sodium supplementation during or after exertion improves hydration. We hypothesized that it may therefore improve well being after exercise-induced sodium loss. To avoid cognitive-biased interpretations of the taste of salt, we used untasted salt in swallowed capsules to condition preference for the flavor of a drink. In four 90 min exercise sessions, 2-3 days apart, participants drank 100 ml of a novel drink and swallowed a capsule, either empty (placebo), or containing 200, 400 or 600 mg NaCl (n=20 in each group). We found both increases and decreases in flavor preference conditioning, depending on salt dose and level of sweat loss: in groups receiving salt supplementation, high levels of sweat loss induced greater flavor conditioning of preference than low levels of sweating. However, 600 mg NaCl conditioned a flavor aversion relative to placebo, which was greater in exercisers sweating little. We conclude that since untasted salt conditioned flavor preference in direct proportion to the amount of sweat lost, replenishment of the sodium lost in sweat induces a rewarding physiological state. The results provide further evidence for the physiological determinants of human salt appetite, and buttress the evidence that post-ingestive effects condition food preferences. Conditioned flavor preference may also provide a useful measure of the benefits of other nutrient additives in sports drinks.

Adult↗
PubMed2003

Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.

OBJECTIVES: To investigate the screening performance of measuring blood pressure and other variables in identifying those who will develop, or die from, ischaemic heart disease and stroke. To quantify by how much drugs that lower blood pressure will reduce the risk of ischaemic heart disease and stroke in those designated 'screen positive'. DATA SOURCES: MEDLINE, Cochrane collaboration and Web of Science databases; Stroke registries; Health Survey for England; Office of National Statistics; BUPA (British United Provident Association) study. REVIEW METHODS: Relevant cohort studies and randomised trials were identified and analysed. Statistical analysis was used to determine drug efficacy and adverse effects. RESULTS: Lowering blood pressure by 5 mmHg diastolic reduces the risk of stroke by an estimated 34% and ischaemic heart disease by 21% from any pre-treatment level; there is no threshold. These estimates, from cohort studies, have been corroborated by the results of randomised trials in persons with high, average and below average levels of blood pressure. In spite of its importance in causing cardiovascular disease blood pressure is a poor predictor of cardiovascular events. Its poor screening performance is illustrated by the findings that in the largest cohort study, persons in the top 10% of the distribution of systolic blood pressure experienced only 21% of all ischaemic heart disease events and 28% of all strokes at a given age. Combining several reversible risk factors adds little to the screening performance of blood pressure alone; for example the 25% of men aged 5564 at highest computed risk (> or =1%) experience only 46% of all ischaemic heart disease events. The main methods of screening should be to identify all persons with a history of cardiovascular disease events (for example identifying patients at the time of hospital discharge following a first myocardial infarction detects 50% of all heart disease deaths in a population at a false positive rate of 12%), and to use a person's age. Identifying everyone with a history of myocardial infarction or stroke in a population and everyone aged 55 or more would include 98% of all deaths from ischaemic heart disease and stroke. The five main categories of blood pressure lowering drugs, thiazides, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists and calcium channel blockers, significantly reduce blood pressure from all pre-treatment levels though the extent of the blood pressure reduction increased with pre-treatment blood pressure. The reductions were similar at standard dose for the five categories; average reduction was 9.1 systolic and 5 diastolic. The effect of combinations of two drugs on blood pressure was additive. No effect of age was apparent, given blood pressure. There were no serious metabolic consequences of using these drugs in standard dose. CONCLUSIONS: The evidence presented indicates that three drugs in combination may reduce stroke by about two-thirds and ischaemic heart disease by half. The report suggests that the term hypertension should be avoided because it is not a disease and it implies another category (normotensives) who would not benefit from lowering blood pressure. Blood pressure reduction using combinations of safe, well-established drugs is effective in preventing cardiovascular events. It is therefore suggested that such preventive therapy be considered more widely in people who by virtue of existing disease or simply age are at risk of a heart attack or stroke regardless of initial blood pressure.

Antihypertensive Agents↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗