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Biomedical subjects

M L Netzloff

Publications and source records attributed to M L Netzloff.

8 recordsLinked to original sources
PubMed1979

Folate antagonism following teratogenic exposure to diphenylhydantoin.

Previous studies have reported indirect evidence for the mediation of folate antagonism in the induction of malformations by diphenylhydantion. We have demonstrated that a teratogenic regimen of folate-deficiency and antagonism using 9-methyl PGA in the rat produces significantly decreased rates of oxygen consumption in the maldeveloping embryos. The present study reports similar reductions in oxygen uptake by mouse embryos from mothers treated with teratogenic doses of diphenylhydantoin, and documents a significant depression of the actual folate levels in such embryos. The differences are less significant with lower doses of diphenylhydantoin, and do not occur with a nonteratogenic dose.

Abnormalities, Drug-Induced↗
PubMed1976

Adverse drug reactions leading to hospitalization in children.

During a three-year period of prospective epidemiologic surveillance for adverse drug reactions in a pediatric population, 72 (2.0%) of 3,556 medical admissions were the result of adverse drug reactions. Antineoplastic drugs were most frequently cited as causing a reaction leading to admission. Approximately 40% of the reactions were severe, and four reactions contributed to death.

Adolescent↗
PubMedDate not supplied

Induction of urogenital neoplasia and abnormalities from prenatal exposure to diethylstilbestrol.

The occurrence of vaginal clear cell adenocarcinoma in young women following exposure in utero to diethylstilbestrol (DES) is now well documented. In addition to this carcinogenic potential. DES has been shown to be teratogenic. In females, the DES-related malformations include vaginal adenosis, transverse ridges of the vagina or cervix and uterine abnormalities. Although no neoplasms have been observed in DES-exposed males, malformations of the epididymis, testes and phallus are relatively common and may result in infertility. The carcinogenic mechanism of DES may be either a direct induction of malignant potential in vaginal cells or a teratogenic effect causing ectopic Müllerian epithelium which could be exposed later to mutagenic agents in the vagina. The absence of malignancy in DES-exposed males may favor the latter hypothesis since male Müllerian remnants are internal structures and thus would not be exposed to surface carcinogens.

Adenocarcinoma↗
PubMedDate not supplied

Medullary carcinoma of the thyroid in the multiple mucosal neuromas syndrome.

The clinical features of the multiple mucosal neuromas (MMN) syndrome permit the recognition of these patients and their potential development of the associated medullary thyroid carcinoma (MTC). The distinctive physical appearance caused by the mucosal neuromas, the Marfanoid habitus and, occasionally, the positive family history aid in establishing the diagnosis. Neurogangliomas are frequently present in the gastrointestinal tract of these patients who may have megacolon, constipation and diarrhea. The third instance of the MMN syndrome is reported in the newborn as intestinal obstruction. It is suggested that the syndrome be considered in the differential diagnosis of Hirschsprung's disease and bowel obstruction in the neonate. Serum calcitonin measurements following stimulation by calcium or pentagastrin infusion reliably detect incipient MTC and may be used to select those MMN patients requiring thyroid surgery. Recognition of patients with the MMN syndrome and subsequent calcitonin screening and early surgical intervention will significantly reduce the chance of their developing terminal MTC. All MMN patients with mucosal neuromas or intestinal neurogangliomas should have such evaluations at least yearly. Relatives who are at risk for inheriting this dominant disease should be similarly evaluated, regardless of their normal appearance.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Enzyme polymorphism and function during embryonic development.

Alterations in multiple molecular forms of enzymes have been described during normal embryogenesis. Changes in electrophoretic patterns, which differ from the normal isozyme ontogeny, occur in embryos and their yolk-sacs during incipient maldevelopment secondary to teratogen exposure. One such isozyme change, in response to a teratogenic regimen using 9-methyl pteroylglutamic acid (PGA), is persistence of lactate dehydrogenase-5 (LDH-5) beyond its time of normal involution in the rat yolk-sac. Since LDH-5 is an allosteric regulatory enzyme which favors anaerobic metabolism, the cellular respiration of 9-methyl PGA-treated embryos was investigated and found to be depressed. However, no changes were found in the oxidative metabolism of visceral yolk-sacs from similarly treated pregnancies. A possible explanation for the unchanged oxygen consumption is the observed simultaneous quantitative alterations in other LDH-yolk-sac isozymes following 9-methyl PGA treatment. Other potential causes include known changes in isozymes other than LDH, limitation of enzyme function by its substrate or co-factor or the presence of a functionally inert LDH-5 isozyme. Changes in LDH and other isozyme patterns and their associated metabolic alterations may eventually prove useful in predicting chemical teratogenicity.

Animals↗
PubMedDate not supplied

The effects of drugs on embryonic development.

A review of the literature demonstrated the difficulties in evaluating the teratogenic effect of drugs in man. Since epidemiologic studies provide suggestive rather than definitive data and results of the current drug testing in laboratory animals may not be applicable to man, the need to develop alternative methods of predicting teratogenicity was apparent. To develop such techniques by studying a possible mechanism of teratogenesis, experiments were performed using a teratogenic folic acid-deficiency and antagonism with 9-methyl pteroylglutamic acid in the pregnant rat. Embryos developing abnormally in response ot this regimen consumed oxygen at a significantly decreased rate. Similar significant reductions in oxygen consumption were found both in rat embryos malforming in response to maternal vitamin A acetate administration, and in mouse embryos in response to teratogenic doses of diphenylhydantoin. It was suggested that such measurements of oxidative metabolism or related techniques may have application in predicting drug teratogenicity and could aid present epidemiologic and empiric approaches to identification of human teratogens.

Animals↗