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Biomedical subjects

R K Miller

Publications and source records attributed to R K Miller.

At least 127 records · Page 7Linked to original sources
PubMed1984

Coexistence of rheumatoid arthritis and sarcoidosis: difficulties encountered in the differential diagnosis of common manifestations.

Two patients with rheumatoid arthritis (RA) and sarcoidosis illustrate the dilemmas posed by their coexistence in the same patient. The first patient with classical RA developed iridocyclitis, interstitial lung disease and cranial neuropathies, initially attributed to extraarticular rheumatoid disease. Subsequent lung and skin biopsy revealed many granulomas consistent with sarcoidosis whereas synovium revealed changes typical for RA. In the second patient with cutaneous and pulmonary sarcoidosis development of persistent erosive polyarthritis and a subcutaneous nodule with typical pathology permitted the diagnosis of coexistent RA. These cases emphasize that uveitis alone or multiple cranial neuropathies are not features of RA and symptomatic interstitial lung disease in patients with RA warrants further investigation.

Adult↗
PubMed1983

Prenatal diazepam: distribution and metabolism in perinatal rats.

Previous investigations have revealed that prenatal exposure to diazepam (DZ) alters brain development and behavior in the offspring of rats and mice. In order to understand how DZ may affect the developing nervous system it is necessary to examine its metabolic fate in the neonate. It is therefore the aim of this study to investigate the disposition, metabolism, and persistence of DZ in the neonate. Dams were injected s.c. with 2.5 mg/kg of 14C DZ (10 muCi/day) on days 13-20 of gestation and their litters were fostered at birth. Dams killed within 24 hours postpartum and neonates killed at postnatal days 0, 10, and 20 were analyzed for 14C activity. Brain levels (pmoles DZ and metabolites/100 mg tissue SE) were 3.4 +/- 0.3 in the dam and in the neonates were 3.2 +/- 0.3 (day 0), 3.4 +/- 0.3 (day 10), and undetectable at day 20. Neonatal peripheral tissue 14C activity was undetectable by day 10. Brain regional analysis indicates 14C is highest in the colliculi at day 0, but not at day 10. Brain levels of DZ, oxazepam (OXA), N-desmethyldiazepam (NDZ), and the glucuronide (GLU) determined by high-performance liquid chromatography (HPLC), were GLU (49%), DZ (28%), and NDZ (24%) in the dam; GLU (52%), DZ (24%), and NDZ (25%) in the day 0 neonate; and GLU (32%), DZ (12%), NDZ (39%), and OXA (19%) at day 10. The distribution and metabolism of 14C DZ that persists in the neonate following prenatal exposure differs from that which occurs in the dam.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Prenatal diazepam exposure: effects on auditory temporal resolution in rats.

The maturation of temporal acuity in the auditory system of the rat was evaluated following prenatal exposure to diazepam (DZ; 0, 2.5, 10 mg/kg to the dam on each of the last 8 days of gestation). Acuity was defined by the effectiveness of brief silent periods in white noise (gaps) as in inhibitors of an immediately subject acoustic startle reflex. In uninjected control rats the gaps became effective at 25-28 days of age, and onset was delayed in prenatally exposed animals according to dose. No DZ was present in the rat offspring at animals in adulthood (0, 0.5, 1.5, 4.5 mg/kg). These injections reduced the inhibitory effect of the gap on startle behavior in all animals, but less so in those previously exposed to DZ in utero. The threshold of temporal acuity in the rat approximates that found in humans and the function matures at the same relative rate in the two species. Further, administration of DZ in the adult human has the same effect on temporal acuity in the auditory system as it does in the adult rat. There are presently no data available on the effects on human auditory development of exposure to DZ in utero. The data we present have the importance of temporal acuity in the perception of speech and, thus, in the maturation of language ability.

Animals↗
PubMed1983

Fetal pulmonary maturity: relationship between optical density (650 nm) to the lecithin/sphingomyelin ratio and phosphatidylglycerol in amniotic fluid.

An optical density value greater than or equal to 0.15 at A650 n m of amniotic fluid obtained through transabdominal amniocentesis from a high risk obstetrical population, which excluded diabetes mellitus, isoimmunization, and amniotic fluid infection, correlated 98.6% with a mature lecithin to sphingomyelin ratio (L/S) greater than or equal to 2.0% and 41.6% with the presence of phosphatidylglycerol (PG). The corresponding false positive rates were 1.4% and 16.8%, respectively. In 30 infants delivered within 48 h of testing, A650 n m greater than or equal to 0.15 correlated 100% with absence of respiratory distress syndrome. A650 n m is not recommended for Rhesus immunized gestations, diabetic pregnancies and amniotic fluid infection due to a high false positive rate with A650 nm compared to L/S and PG.

Amniotic Fluid↗
PubMed1983

Coexistence of Reiter's syndrome and rheumatoid arthritis in a genetically susceptible individual.

A patient is presented who had features of Reiter's syndrome for 10 years before developing features of rheumatoid arthritis. Diagnostic criteria for both diseases are fulfilled, and HLA typing revealed the presence of both B27 and DR4 antigens. The coexistence of Reiter's syndrome and rheumatoid arthritis appears to have occurred in an individual genetically susceptible to both diseases.

Adult↗
PubMed1983

Perinatal toxicology: its recognition and fundamentals.

Perinatal toxicology is the study of aberrant or toxic responses to environmental agents when exposure occurs from conception through the neonatal period. The current increased interest in perinatal toxicology reflects the concern of both society and the individual in the resultant deficits induced by exposure to agents in the workplace, home, environment and by therapeutic intervention during early development. Not only is differentiation during organogenesis (the first eight weeks in human gestation) a highly susceptible period to the induction of malformations, but the fetal/neonatal developmental phases are just as sensitive for certain developmental deficits. Long-term postnatal evaluations are in most instances critical for the documentation of fetal/neonatal functional defects, which include carcinogenesis, behavioral impairment, endocrine and immune dysfunction. Ethylnitrosourea, estrogens (diethylstilbestrol), and cadmium are discussed in relationship to specificity of their fetal effects, long-term follow-up, and possible mechanisms of toxic action.

Animals↗
PubMed1983

Radiologic diagnosis of diethylstilbestrol induced teratogenesis in rats.

Radiographs were used for the assessment of diethylstilbestrol-induced teratogenesis of the urogenital system of rats. Lesions such as female hypospadias were demonstrable with a 4:1 magnification of radiographs that were not observed using subgross dissection and histologic step sections.

Abnormalities, Drug-Induced↗
PubMed1982

Diethylstilbestrol: placental transfer, metabolism, covalent binding and fetal distribution in the Wistar rat.

The disposition of [14C]diethylstilbestrol (DES) was investigated in the near-term pregnant Wistar rat. Both constant maternal i.v. infusions and direct fetal i.p. injections of [14C]DES were utilized as exposure routes. Maternal femoral vein infusions (total dose: 0.3-0.4 mg of DES/kg of maternal b.wt.) resulted in a stable maternal plasma level of DES during a 3-hr period. At 3 hr, fetal plasma levels were 2 to 3 times higher than maternal plasma DES. The chorioallantoic placenta and visceral yolk sac concentrated DES to levels 5 to 7 times that in the maternal plasma. DES was highly concentrated in the extraembryonic membranes and did maintain high fetal plasma levels of DES. Fetal reproductive tract had total 14C-activity levels 20 to 25 times higher than those in maternal plasma. The extractable 14C-activity in the reproductive tract was 20% DES, 15% glucuronides and 65% oxidative metabolites (beta-dienestrol, 4-OH-propiophenone, omega-OH-DES + unknowns). Fetal liver contained DES (approximately 2%), glucuronides (75%) and oxidative metabolites (approximately 20%). 14C analysis of the whole fetus indicated that the DES was 75% and glucuronides was 25%. Maternal and fetal liver had similar metabolites. Direct fetal injections of [14C]DES resulted in similar metabolite profiles in fetal tissues. The degree of covalent binding of [14C]DES to cellular constituents was tissue-specific, especially the fetal reproductive tract. Thus, DES and its oxidative metabolites were concentrated in the fetus and selected fetal tissues. It is proposed that both the estrogenic activity of DES and the potential reactivity of its metabolites may be responsible for the toxicity expressed in the fetus. Inasmuch as direct fetal injections of [14C]DES resulted in high tissue localization of both oxidative and conjugative metabolites within the fetus, it is suggested that fetal tissues may metabolize DES.

Animals↗
PubMed1981

Macromolecule transfer in the human trophoblast: transcobalamin II-vitamin B12 uptake.

The accumulation of the large and hydrophilic IgG, TC II-B12 and B12 molecules is demonstrated for the first time in a human placental system which has metabolic and physiological functions. A trypsin-sensitive component is present in the human term placental uptake of TC II-B12, for which a placental membrane receptor has been previously identified; this component is absent for the accumulation of free B12, which has no known receptor. Analyses of the cytosol and incubation media indicate degradation, binding and release of TC II-B12 and B12 as TC II-B12, free B12 and TC I-like complexes. It is suggested that the human placental tissue slice be used for studies involving the binding, uptake and processing of macromolecules as exemplified by TC II-B12.

Blood Proteins↗
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

Prenatal exposure to diazepam alters behavioral development in rats.

Characteristic potentiation of rat locomotion responses and acoustic startle reflexes that normally appear in the third postnatal week was absent in rats exposed to diazepam during the third week of gestation. Loss of these behaviors suggests a long-term effect that may result from changes in cellular development. Tissue undergoing neuronal differentation may be especially sensitive to drugs that act on the central nervous system, and the period in which differentiation occurs is perhaps critical for the induction of changes that are later expressed as altered behavior.

Animals↗
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↗