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Biomedical subjects

N A Holtzman

Publications and source records attributed to N A Holtzman.

At least 19 recordsLinked to original sources
PubMed1992

The diffusion of new genetic tests for predicting disease.

This paper examines the pathways by which new genetic tests will become available to the public. In view of the scarcity of genetic specialists, the pathway is likely to involve primary care physicians. Other pathways entail state-mandated testing, community-based programs, or testing by laboratories without much involvement of primary care physicians. When testing does become available the "destination" will be either family-centered testing or population-oriented screening. The deterrent to screening will not be the inability to detect disease-causing mutations but the costs and attitudes of providers and the public. When tests are provided primarily to provide information about risks to future children, some people will oppose screening on religious or moral grounds. When there are no inexpensive treatments, some will fear that insurance companies and employers will use tests to deny them health care coverage. Some may not want to know their risks for disorders about which little can be done. For common, multifactorial disorders, genetic tests will have low predictive value. Because of these problems, the decision to be tested, regardless of the destination, requires that "testees" be fully informed and consent to testing. When acceptance rates are low, screening is less likely to be cost-effective; family-centered testing becomes the default destination.

Genetic Diseases, Inborn↗
PubMed1991

Effectiveness of an antihistamine-decongestant combination for young children with the common cold: a randomized, controlled clinical trial.

We tested the hypothesis that antihistamine-decongestant combinations cause no clinically significant relief of the symptoms of upper respiratory tract infections in young children by randomly assigning 96 children to one of three treatment groups: antihistamine-decongestant, placebo, and no treatment. There were no differences among the three study groups in the proportion of children considered "better" overall by the parent 48 hours after the initial assessment (drug, 67%; placebo, 71%; no treatment, 57%; p = 0.53). There were no differences among groups in individual or composite symptom score changes. Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms. In the proportion of parents believing that their child needed medicine, there was no difference between those who consented to participate and those who refused. Parents who wanted medicine at the initial visit reported more improvement at follow-up, regardless of whether the child received drug, placebo, or no treatment. We conclude that there is no clinically significant improvement in symptoms of upper respiratory tract infection, including no significant placebo effect, in young children for whom an antihistamine-decongestant is prescribed.

Brompheniramine↗
PubMed1988

Genetic variation in nutritional requirements and susceptibility to disease: policy implications.

I have considered several questions that should be answered in order to develop rational public policy for preventing disability and premature death for common disorders for which genes play a role and for which nutritional modification within the normal range can be effective. The sensitivity and predictive value of screening tests, the increment in improved outcomes from screening compared with population-wide changes in diet; the benefit, if any, to be derived from diet modification for those not identified by screening; and the reliability of the laboratories performing the test are some of the factors to be considered. We must bear in mind that many of the common disorders for which we will soon have tests at the gene or gene-product level result from the interaction of multiple factors, both environmental and genetic. Genetic screening will detect only a small proportion of all those destined to manifest a specific disorder, such as coronary artery disease or colon cancer. Dietary modification will also be only one of several interventions that will be efficacious for certain disorders. In some of these cases, genetic screening will prove to be an effective adjunct to general nutritional changes whereas in others it will have little utility and in still others it could play the predominant role in preventing or reducing the severity of the disorder. If we are to reduce the burden of disease most effectively, we cannot ignore factors in our environment and social structure that limit people's ability to control their own health.

Adult↗
PubMed1987

On the ability of birth defects monitoring to detect new teratogens.

Recent concerns have been raised about the ability of birth defects monitoring programs to detect increases in the incidence of birth defects following the introduction of new teratogens. The authors illustrate how most monitoring programs in the United States and Europe are limited in their ability to detect new teratogens because of a combination of parameters: the small population size, the low population frequency of exposure to the new teratogen, the weakness of many suspected teratogens (measured in terms of relative risk R), the low background rate, and the etiologic heterogeneity in the measured defects. In a system that monitors 25,000 births per year, it can be shown that although a new teratogen such as thalidomide (R = 175) can lead to a significant increase in the number of observed cases in 1-2 weeks of monitoring, even strong teratogens such as valproic acid and isotretinoin (R = 20-25) require more than 20 years of monitoring to show a significant increase in the number of cases because of low exposure frequency. Also, most mild to moderate teratogens (R = 2-5) can be totally missed. To improve the ability of birth defects monitoring programs to detect new teratogens, it is suggested that surveillance systems ought to examine subsegments of the population with maximal exposure potential, classify birth defects into more etiologically homogeneous groups, and expand the sample size of the monitored population.

Abnormalities, Drug-Induced↗
PubMed1987

Prenatal screening and pregnant women's attitudes toward the abortion of defective fetuses.

We studied the attitudes of 490 pregnant women toward the abortion of defective fetuses. Three hundred of these women were participating in a prenatal screening program for neural tube defects. Although theoretical accounts of the effects of behavior on attitude would suggest that participation in a screening program would affect abortion attitudes, evidence in support of such an association was weak. The overwhelming majority of women, regardless of whether they had participated in the screening program, believed that women are justified in having an abortion in the face of fetal abnormality. There was a sharp increase in the number of screening program participants who said they would have an abortion when the probability of the fetus being affected with a neural tube defect rose from 95 per cent to 100 per cent.

Abortion, Induced↗
PubMed1987

Maternal cigarette smoking and oral clefts: a population-based study.

Analyses of 1984 data from the Maryland Birth Defects Reporting and Information System indicate that mothers of infants with oral clefts (cleft lip with or without cleft palate; and cleft palate) smoked more during pregnancy than mothers of infants with other defects (odds ratio OR of 2.56 and 2.39, respectively). There was a dose-response relation between the daily amount smoked and the risk of clefting. Adjustment for available confounding variables did not account for the association between smoking and oral clefts.

Cleft Lip↗
PubMed1986

Effect of age at loss of dietary control on intellectual performance and behavior of children with phenylketonuria.

We determined the effect on intellectual performance and behavior of the age at which dietary control was lost in 119 10-year-old children with phenylketonuria (PKU) who had started on a diet low in phenylalanine before the age of 65 days. The children's diets were considered to be out of control when their blood phenylalanine concentration persistently exceeded 15 mg per deciliter. The age at which control was lost was the best, and frequently the only, predictor of the child's IQ at the age of 8 or 10 years and of the deficit in the child's IQ as compared with those of his or her unaffected siblings or parents. The age at which control was lost was also the best predictor of the deficit in scores on the Wide Range Achievement Test of children with PKU at the age of eight, as compared with their unaffected siblings, and of behavior problems (Louisville Behavior Checklist). Variables that were not significant included the maximal phenylalanine concentration before dietary therapy, the age at which treatment was started, and the family's coping abilities. The greatest deficiencies in all of these outcomes were observed among children who were out of dietary control before the age of six years. The highest correlation between the IQs of the children with PKU and their respective parents was observed among the children still on the diet at the age of eight years; the lowest, among those who had poor dietary control before the age of six. These findings suggest that phenylalanine restriction should continue after the age of eight years in children with PKU.

Adolescent↗
PubMed1986

A randomized trial of oral iron on tests of short-term memory and attention span in young pregnant women.

Recent studies suggest that infant behavior and psychological test performance are impaired by iron deficiency and may be improved by iron. Comparable studies have not been performed in older populations. Young women early in pregnancy whose nutritional intake may be impaired by poverty constitute a high-risk population. Women aged 14-24 years coming for prenatal care at or before 16 weeks gestation whose hematocrits were greater than or equal to 31% were randomized in a double-blind trial to receive vitamins supplemented with iron (experimental group) or vitamins alone (controls). Hematologic status and tests of short-term memory and attention span were assessed at entry and conclusion of the one-month treatment period. The experimental group showed significant improvement on the most sensitive measure of short-term memory and three subtests. On comparison of the change between initial and final scores, the experimental group showed significant or borderline greater improvement than controls on three tests. These results indicated a beneficial effect of iron therapy on psychometric test-score performance.

Adolescent↗
PubMed1986

Monitoring for congenital malformations.

Many countries instituted birth defects monitoring systems in the wake of the thalidomide tragedy. Having these systems in place will shorten the time before an alarm is signaled, should a teratogen of the potency of thalidomide be introduced. However, with stronger laws and regulations for testing drugs for adverse reproductive outcomes, a tragedy on the scale of thalidomide from ingestion of prescribed drugs by pregnant women is unlikely. Prospective parents could be exposed at the critical times to new physical, infectious, or nondrug chemical agents teratogenically as potent as thalidomide. (Teratogenic agents whose widespread use antedates monitoring will not cause rate changes or clusters detectable by monitoring.) What seems more likely is that the introduction of "weakly" teratogenic agents, or the inadvertent use of new drugs that are teratogenic, like isotretinoin, will be responsible for increases in birth defects. In neither of these situations are large numbers of cases likely to accumulate in short periods of time, particularly in the relatively small catchment areas (fewer than 50 to 100,000 births per year) of many monitoring programs. In addition to having to cope with this problem of rare outcomes, many monitoring systems have not been able to obtain complete ascertainment of CMs, at least not from single, rapidly reporting sources. Two remedies to these inadequacies are possible: Expand the catchment area. All births in the US, for instance, could be monitored if information on specific CMs was included on birth certificates, which were then transmitted to a central agency that could analyse the data rapidly. Alternatively, if different monitoring systems had comparable methods of ascertainment and diagnostic classifications, their data could be pooled with greater reliability than is currently possible. CMs in newborns are only one indicator of teratogenicity. At least 20% of all conceptions end in spontaneous abortions. A much higher proportion of abortuses have chromosome abnormalities, congenital malformations, or both, than newborns. The time necessary for such outcomes to manifest after the introduction of a new teratogen could be considerably shorter than the time before significant increases of CMs occurred in liveborns and stillborns. Monitoring the spontaneous abortion rate or chromosomal and other abnormalities in abortuses would be an important adjunct to monitoring newborns. However, since some teratogens may only cause CMs in newborns, the current approach to monitoring should not be abandoned. Moreover, the problems of ascertainment encountered in monitoring newborns are greater still in monitoring abortuses.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗