Search PubMed⌕ Search

Biomedical subjects

A A Levin

Publications and source records attributed to A A Levin.

At least 73 records · Page 4Linked to original sources
PubMed1985

The influence of maternal cadmium exposure or fetal cadmium injection on hepatic metallothionein concentrations in the fetal rat.

The ability of Cd to induce the synthesis of fetal hepatic metallothionein (MT) was investigated in rat fetuses exposed to Cd throughout gestation via the mother's drinking water or injected directly with Cd through the uterine wall on Day 18 of gestation. On Day 21 all dams were killed and fetal and maternal tissues were removed. Tissue MT, Zn, Cu, and Cd concentrations were measured. Fetal hepatic Cd concentration was increased only at the high maternal Cd exposure, whereas Zn concentration was significantly reduced by Cd exposure. Both fetal liver and kidney MT were reduced following maternal Cd exposure. Unlike maternal hepatic MT, fetal hepatic MT was not increased after maternal Cd exposure nor did the direct injection of Cd into the 18 days of gestation fetus induce fetal MT synthesis. These data suggest that fetal rat liver is incapable of synthesizing MT in response to Cd, possibly because Cd is not transported to the site of MT synthesis in the fetal system. Furthermore, neither the route of exposure, the duration of prenatal Cd exposure, nor the stage of gestation appear to account for the differences observed between fetal and adult hepatic MT induction by Cd.

Administration, Oral↗
PubMed1984

Discontinued use of intrauterine contraceptive device and pregnancy loss.

To evaluate the risk of spontaneous abortion among former intrauterine contraceptive device (IUD) users, we compared the contraceptive history of 328 women with a spontaneous abortion up to 28 weeks' gestation with that of 1715 women having a term delivery. A similar percentage of case and comparison subjects reported prior IUD use as well as IUD use within the year before pregnancy. However, IUD use lasting more than 12 months was associated with a 1.5-fold increase in the crude risk of spontaneous abortion up to 28 weeks' gestation (p less than 0.05), a 1.8-fold increased risk of first-trimester spontaneous abortion, and a 1.7-fold increased risk of incomplete abortion (p less than 0.01). The results were not altered by control of individual confounding factors. When confounding factors were controlled simultaneously in a multiple logistic regression analysis, the relative risks were 1.4, 1.7 and 1.6, respectively; however, they were no longer statistically significant. The results suggest that prolonged IUD use may be associated with a modest increase in risk of subsequent spontaneous abortion.

Abortion, Incomplete↗
PubMed1984

Complications of surgery in hypothyroid patients.

Hypothyroidism has generally been considered a contraindication to surgery. To determine the actual risks of perioperative complications in hypothyroid patients, the clinical courses of 40 hypothyroid surgical patients (serum thyroxine concentration 1.9 +/- 1.0 micrograms/dl) were retrospectively compared with those of 80 control patients matched for age, sex, and operative procedure. The two study groups were comparable in preoperative anesthetic physical class, prevalence of other medical conditions, and year of operation. During noncardiac surgery, intraoperative hypotension was encountered more frequently in the hypothyroid patients than in the control patients (61 versus 30 percent, p less than 0.05). Cardiac surgery was complicated by heart failure more often in the hypothyroid patients (29 versus 6 percent, p less than 0.05). Postoperatively, the hypothyroid patients more commonly had gastrointestinal (19 versus 1 percent, p less than 0.02) and neuropsychiatric (38 versus 18 percent, p less than 0.02) complications than control patients. Despite comparable rates of perioperative infection (38 versus 33 percent, p = NS), the hypothyroid patients less frequently manifested fever (35 versus 79 percent, p less than 0.001). There were no differences in perioperative blood loss, duration of hospitalization, or the prevalences of perioperative arrhythmia, hypothermia, hyponatremia, delayed anesthetic recovery, abnormal tissue integrity, impaired wound healing, pulmonary complications, or death. Preoperative clinical and chemical features of hypothyroidism were not useful in defining a subgroup of patients at special risk. Thus, surgery in hypothyroid patients is associated with an increased risk of several minor perioperative complications, which should be anticipated and preemptively managed in the course of their anesthetic and surgical care.

Adult↗
PubMed1984

L-Thyroxine therapy in subclinical hypothyroidism. A double-blind, placebo-controlled trial.

The indications for treating patients with subclinical hypothyroidism (normal serum thyroxine and free thyroxine levels, but elevated serum thyrotrophin levels) are poorly defined. In this study, 33 patients with subclinical hypothyroidism were randomly assigned in a double-blind manner to receive placebo or L-thyroxine therapy and were followed for 1 year with thyroid function tests, serum lipid measurements, basal metabolic rate and systolic time interval determinations, and a questionnaire on hypothyroid symptoms. The placebo group showed no changes in thyroid function or peripheral indices of thyroid hormone action. In the thyroxine-treated group, serum lipids and the mean systolic time interval did not change, but the systolic time intervals became normal in the 5 patients with the most abnormal baseline values. Symptoms improved in 8 of 14 patients receiving thyroxine and in 3 of 12 patients receiving placebo (p less than 0.05). L-Thyroxine therapy may be useful for patients with subclinical hypothyroidism with abnormal myocardial contractility or symptoms consistent with mild hypothyroidism, or both.

Adult↗
PubMed1983

Agranulocytosis associated with antithyroid drugs. Effects of patient age and drug dose.

The records of all patients with antithyroid drug-related agranulocytosis at two Boston hospitals (Group 1, 14 patients), as well as the published case reports of 36 patients with this syndrome (Group 2) were reviewed. The clinical characteristics of these patients were then compared with those of 50 hyperthyroid patients who had taken antithyroid medication without untoward hematologic reactions (Group 3). The mean ages of patients in Group 1 and Group 2 were significantly greater than that of Group 3 (50.6 +/- 16 years versus 35.7 +/- 13.7 years, p less than 0.001; 46.3 +/- 18.7 years versus 35.7 +/-- 13.7 years, p less than 0.02). By chi-square analysis, the relative risk of developing agranulocytosis in patients over age 40 was 6.4 times that among younger patients (p less than 0.001). The mean doses of methimazole in Group 1 and Group 2 were significantly higher than that in Group 3 (43.8 +/- 9.9 mg/d versus 29.5 +/- 10.4 mg/d, p less than 0.001; 40.7 +/- 15.7 mg/d versus 29.5 +/- 10.4 mg/d, p less than 0.02), with and 8.6-fold increased risk of agranulocytosis with doses greater than 40 mg/d (p less than 0.01). In contrast, the mean doses of propylthiouracil did not differ among the three groups. These data suggest that antithyroid drugs should be administered cautiously to patients over age 40. Because no cases of agranulocytosis were seen with methimazole doses less than 30 mg/d, low-dose methimazole therapy may be safer than high-dose therapy or treatment with conventional doses of propylthiouracil.

Adolescent↗
PubMed1982

Ectopic pregnancy and prior induced abortion.

We compared the prior pregnancy histories of 85 multigravid women with an ectopic pregnancy and 498 multigravid delivery comparison subjects. We found a relationship between the number of prior induced abortions and the risk of ectopic pregnancy: the crude relative risk of ectopic pregnancy was 1.6 for women with one prior induced abortion and 4.0 for women with two or more prior induced abortions; however, use of multivariate techniques to control confounding factors reduced the relative risks to 1.3 (95 per cent confidence interval, 0.6-2.7) and 2.6 (95 per cent confidence interval, 0.9-7.4), respectively. The analysis suggests that induced abortion may be one of several risk factors for ectopic pregnancy, particularly for women who have had abortions plus pelvic inflammatory disease or multiple abortions.

Abortion, Induced↗
PubMed1981

Cadmium: placental mechanisms of fetal toxicity.

Subcutaneous injections of 40 mumol/kg of CdCl2 given to rats on day 18 of pregnancy produced a high incidence of fetal death and placental necrosis. Fetuses directly injected with CdCl2 in utero were resistant to cadmium levels far in excess of fetal levels associated with fetal death following maternal injection. Thus cadmium-induced fetal death was not the result of a direct effect of cadmium on the fetus. Similarly, exposure of fetuses or dams to Cd-metallothionein did not produce fetal death. Placental histological changes and high placental accumulations of cadmium suggested placental mechanisms for the toxicity. Histological changes were observed as early as 12 hours after injection and were characteristic of local circulatory responses. Blood flow measurements with radiolabelled microspheres indicated that uteroplacental blood flow was decreased 40 per cent and 75 per cent at 12-16 hours and 18-24 hours after injection. Studies on the initial responses of the placenta to cadmium exposure revealed that biochemical and ultrastructural changes could be observed in the placenta prior to alterations in blood flow and fetal death. No ultrastructural changes were observed in the uterine vascular endothelium. Thus cadmium-induced fetal death was not the result of direct effects of cadmium but may be the result of a placental effect of the heavy metal. A proposed mechanism for the induction of fetal death is that high placental accumulations of cadmium result in trophoblastic damage which leads to a local circulatory response to the injured tissues and a decrease in uteroplacental blood flow. It is the decrease in nutrient and oxygen transport to the fetus that results from trophoblastic damage and blood flow alterations that ultimately induce fetal death.

Animals↗
PubMed1980

Association of induced abortion with subsequent pregnancy loss.

We compared prior pregnancy histories of two groups of multigravidas--240 women having a pregnancy loss up to 28 weeks' gestation and 1,072 women having a term delivery. Women who had had two or more prior induced abortions had a twofold to threefold increase in risk of first-trimester spontaneous abortion, loss between 14 to 19 and 20 to 27 weeks. The increased risk was present for women who had legal induced abortions since 1973. It was not explained by smoking status, history of prior spontaneous loss, prior abortion method, or degree of cervical dilatation. No increase in risk of pregnancy loss was detected among women with a single prior induced abortion. We conclude that multiple induced abortions do increase the risk of subsequent pregnancy losses up to 28 weeks' gestation.

Abortion, Induced↗
PubMed1980

Dept. of Pharmacology & Toxicology, University of Rochester, School of Medicine and Dentistry, New York.

Fetal death in rats was produced by subcutaneous injections of CdCl2 (40 mumoles/kg) on day 18 of pregnancy. The incidence of fetal death following these maternal injections was 74.9%, with mean (+/- SD) fetal cadmium burdens of 8.6 +/- 4.4 nmoles. To separate maternal from fetal effects of cadmium, doses of CdCl2 up to 60 mumoles/kg fetal weight were injected directly into fetuses on day 18 of gestation. Fetal viability was then determined on gestational day 21. Following direct fetal injection, mean fetal body burdens of cadmium were 74.6 +/- 34.8 nmoles, but the incidence of fetal dealth was only 11.5%. The high incidence of fetal death following maternal exposure to CdCl2 is not solely explained by the direct effects of CdCl2 on the fetus. Thus, the fetal toxicity of cadmium may be the result of some extra-fetal mechanism such as maternal toxicity or the observed placental necrosis.

Animals↗
PubMedDate not supplied

Synthetic oligonucleotides: the development of antisense therapeutics.

Antisense therapeutics using synthetic oligodeoxynucleotides (ODNs) are currently being evaluated in clinical trials for cancer, inflammation, and viral diseases. These macromolecules afford a unique opportunity to treat disease at the molecular level. The specificity of these compounds is derived from the genetic code and Watson-Crick base pairing, utilizing an antisense paradigm for the inhibition of translation and the regulation of protein expression. Currently, most antisense ODNs in development contain a phosphorothioate (P=S) backbone. Additional modifications primarily involve the 2' position on the ribose or modification of the nucleotide linkages of the backbone. To date, no toxicities in animal models appear related to inhibition of the pharmacologic target, rather toxicities induced by P=S ODNs appear similar and are independent of pharmacologic target. In general, toxicities correlate well with pharmacokinetic or tissue distribution parameters. In primates, the primary acute effects are associated with complement activation and the systemic effects associated with accumulation of high concentrations of P=S ODNs in the kidneys. In rodents, the primary effect is an immune stimulation characterized by splenomegaly, lymphoid hyperplasia, and mononuclear cell infiltrates in multiple tissues. At extraordinarily high doses (15-50 times the targeted clinical doses), hepatocellular and renal tubular degeneration are evident in rodents. Second generation antisense compounds, new routes of administration, and new formulations appear to broaden and improve the application of antisense technology.

Animals↗