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Biomedical subjects

E Miller

Publications and source records attributed to E Miller.

At least 19 recordsLinked to original sources
PubMed2026

Mechanisms of Hexavalent Chromium-Induced Reproductive Toxicity: A Focus on the Ovary and Placenta.

Hexavalent Chromium (Cr(VI)) is a Group A carcinogen, mutagen, and teratogen. Cr(VI) has been used by more than 50 industries, and its contamination of drinking water is widespread across the United States (U.S.). Epidemiological data of women who lived in Willits, California, U.S., indicate that environmental exposure to Cr(VI) adversely affects pregnancy outcomes and the health of their immediate offspring, resulting in a low birth rate, pregnancy loss, and spontaneous abortion, and their children (F1 offspring) experienced birth defects. However, the molecular mechanisms behind Cr(VI)-induced reproductive and developmental toxicity are poorly understood. Cr(VI) enters cells through anion transporters and is rapidly reduced to Cr(III) by endogenous antioxidants within the cell. Cr(III) forms adducts with DNA, which can block DNA replication and transcription; abnormal repair can lead to DNA double-strand breaks, mutations, micronucleus formation, chromosomal abnormalities, and increased genomic instability. Cr(VI) induces oxidative stress via the Fenton reaction, generating free radicals, and depleting antioxidants, thereby promoting apoptosis via p53-dependent and independent pathways, resulting in follicular atresia and accelerated reproductive aging. Antioxidant supplementation with resveratrol, vitamin C, and edaravone mitigates Cr(VI) toxicity in the ovary. Cr(VI) disrupts meiosis in metaphase II oocytes by causing DNA strand breaks, altering F-actin dynamics, disturbing microtubules, and leading to chromosome missegregation. Gestational exposure to Cr(VI) also disrupts placental function through multiple mechanisms by targeting trophoblast lineages. The current review focuses on genotoxicity, oxidative stress, and other mechanisms by which Cr(VI) disrupts the female reproductive and endocrine systems, with particular emphasis on the ovary and placenta.

Hexavalent chromium↗
PubMed1992

The epidemiology of pertussis in England and Wales.

Recovery in the uptake of whole-cell pertussis vaccine from 30% in 1978 to 91% in 1992 has resulted in a major reduction in the incidence of pertussis and in the proportion of cases occurring in pre-school children. This has been accompanied by a decline in pertussis mortality rates, with no deaths reported since September 1990. Seventy-four per cent of the 50 fatal cases reported since 1980 have been infants under one year of age, demonstrating the importance of completing primary immunisation as early as possible after birth. There is no evidence, as yet, that introduction of the accelerated immunisation schedule in June 1990 has reduced the proportion of cases occurring in infants, suggesting that the decline in mortality during the last two years is largely due to indirect protection provided by the current high level of vaccine-induced herd immunity. If 90% coverage is sustained and there is no significant waning of immunity with age, the circulation of Bordetella pertussis should be sufficiently reduced to interrupt the four year epidemic cycle for the first time in the United Kingdom. The hypothesis that vaccine-induced immunity has a serotype-specific component is supported by recent changes in serotype prevalence which have followed the increase in vaccine coverage. Given the successful reinstatement of whole-cell vaccine in the UK immunisation programme, the case for replacing it with a new acellular preparation will require careful evaluation.

Adolescent↗
PubMed1992

Surveillance of HIV infection by voluntary testing in England.

Eighteen laboratories, which together provide primary HIV antibody testing for 43% of the population in England, collaborated in a study to record epidemiological information for all individuals voluntarily tested by them over a five year period. From the 184,113 individuals who had a first test during the study period, it is estimated that 1 in 12 adults in London, and 1 in 50 outside London have been voluntarily tested for HIV since testing became widely available in 1985. The majority of those tested were individuals whose perceived risk was heterosexual exposure. Infection in this group was concentrated in individuals whose partner had an identified risk and in those who had lived in or visited Africa. The rise in antibody prevalence observed in the latter group during 1990/91 may have been partly due to infection recently acquired in the UK. Antibody prevalence in heterosexuals without a high risk partner or a history of exposure abroad also rose during the study period, suggesting a recent increase in transmission through casual heterosexual exposure in the UK. The study also provided strong evidence of continuing high risk behaviour among homosexual men, particularly in the younger age groups. Homosexuals aged under 30 years and living in London had the greatest risk of acquiring HIV infection since 1988.

AIDS Serodiagnosis↗
PubMed1992

An evaluation of color duplex scanning in the primary diagnosis and management of carotid body tumors.

Carotid body tumors present a diagnostic challenge. Despite technologic diagnostic advances, misdiagnosis resulting in blind biopsy or exploration through a limited incision still occur. Color duplex scanning has recently been used to evaluate carotid body tumors in our institution. A characteristic feature of these tumors found with this modality is wide splaying of the carotid bifurcation by a hypervascular mass. Color duplex scanning is the noninvasive modality of choice for the primary diagnosis of carotid body tumors. Additionally, it may be of use in screening for familial carotid body tumors and sequential follow-up of nonoperatively managed tumors.

Adult↗
PubMed1992

Effect of digitalis on norepinephrine kinetics in congestive heart failure.

OBJECTIVE: The aim of this study was to test the hypothesis that digitalis glycosides would reduce sympathetic activity as reflected by forearm venous norepinephrine kinetics in patients with congestive heart failure. BACKGROUND: Digitalis glycosides have been reported to decrease sympathetic nervous system activity with baroreceptor sensitization in experimental animals. Such effects could be of therapeutic importance in congestive heart failure. METHODS: Double-blind randomized assessment was made of the effects of low dose intravenous deslanoside (Cedilanid-D, 0.002 mg/kg body weight) and vehicle on heart rate, arterial pressure, forearm blood flow, plasma norepinephrine, norepinephrine clearance and norepinephrine spillover in nine patients with stable congestive heart failure, New York Heart Association functional class II or III. Open label assessment of the responses to 0.6 mg of deslanoside was made in an overlapping group of seven patients. All measurements were made 30 and 60 min after intravenous injection of drug or vehicle and after 15 min of 30 degrees head-down tilt as a test of the sympathetic response to baroreceptor loading. RESULTS: Heart rate, arterial pressure and forearm blood flow were unchanged by low dose deslanoside. Heart rate decreased slightly with the 0.6 mg dose with the patients in the supine position. Norepinephrine spillover and clearance decreased with time on each study day in the supine position, but no effect was attributable to digitalis. Plasma norepinephrine and norepinephrine clearance and spillover all remained unchanged during head-down tilt on each study day. CONCLUSIONS: Nonpressor doses of deslanoside do not suppress sympathetic activity as reflected by venous norepinephrine and norepinephrine spillover in patients with congestive heart failure. Further, deslanoside did not normalize the sympathetic response to mild baroreceptor loading produced by head-down tilt. These data do not support sympathoinhibition through baroreceptor sensitization as a likely effect of digitalis in congestive heart failure.

Deslanoside↗
PubMed1992

Monoclonal antibodies against LDL further enhance macrophage uptake of LDL aggregates.

Self-aggregates of low density lipoprotein (LDL) are taken up and degraded more rapidly by macrophages than is native LDL. That enhanced uptake is attributable in part to phagocytosis via the LDL receptor pathway. However, arterial macrophages appear to express little LDL receptor activity. The present studies demonstrate an alternative mechanism by which LDL aggregates could contribute to foam cell formation. This could occur by the formation of large immune complexes that are taken up by macrophages via the Fc receptor. When immune complexes were formed with native, soluble LDL and MB47, a monoclonal antibody specific to the apoprotein B domain recognized by the LDL receptor, the subsequent uptake and degradation of the LDL by macrophages were inhibited 50-80% compared with native LDL alone. In contrast, when aggregated LDL was bound to MB47 at a similar molar ratio, the subsequent degradation of the insoluble immune complexes was two- to fivefold greater than that of aggregated LDL alone. The enhanced uptake was abolished when Fab or F(ab')2 fragments of MB47 were substituted for the intact antibody, indicating that the increased uptake was via the Fc receptor pathway. Furthermore, the uptake of the immune complexes of aggregated LDL was reduced by competition for the Fc receptor with heat-aggregated immunoglobulin. There was also an increase in the rate of cellular cholesterol esterification and an increase in macrophage cholesteryl ester mass. Since aggregates of LDL as well as autoantibodies against modified LDL have been demonstrated in atherosclerotic lesions, it is possible that immune complexes of aggregates of modified LDL may be generated in the intima.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Psychological approaches to the management of memory impairments.

Memory impairments are handicapping to those who suffer them, and a number of ways of trying to help those afflicted have been devised. Effective psychological approaches are likely to be based on methods designed either to make the most efficient use of remaining memory capacity, or to alter the environment so as to reduce the demands placed on memory. At present the success of such approaches is limited.

Amnesia↗
PubMed1991

Voluntary antenatal HIV testing--results of a pilot study.

Voluntary testing for antibody to human immunodeficiency virus (HIV) was offered to 4929 antenatal patients attending two hospitals in South Manchester during a 12 month period in 1989/90 in order to assess the feasibility of obtaining seroprevalence data by this method. Of these patients, 1728 (35%) agreed to a named test, 1396 (28%) to an unlinked anonymous test and the remaining 37% declined to be tested. The proportion of women tested increased from 22% to 88% over the period, and was similar in those with and without an identified risk factor for infection. One HIV antibody positive patient was found; she was tested anonymously and had no identified risk. The substantial cost in time and money required to establish the universal voluntary testing programme and the incomplete patient compliance confirm the importance of the unlinked anonymous surveys currently being established in the UK to monitor seroprevalence in sentinel populations.

AIDS Serodiagnosis↗
PubMed1991

Regional and long-term variability of fundus measurements made with computer-image analysis.

We studied the variability of optic disk and peripapillary nerve fiber layer surface contour measurements made by use of computer-image analysis. Six hundred twenty-five measurements of surface contour were made on each eye by use of simultaneous stereoscopic videography. Regional differences in short-term measurement variability were studied in 12 eyes (six normal and six glaucomatous), each imaged nine times over several days. The widths of the 95% confidence interval for the measurements averaged 82 microns for the juxta-papillary surface and 132 microns for the disk surface. Measurements of peripapillary surface contour were significantly less variable than were measurements of the disk surface (P = .000). The greatest variability was detected along large blood vessels and at steep contours. Long-term variability was studied in a separate group of 30 clinically stable patients with glaucoma, each imaged three to six times over a period of more than one year. The widths of the 95% confidence intervals were 132 microns for the peripapillary surface and 217 microns for the disk surface. The long-term variability was significantly greater than the short-term variability (P = .000). The peripapillary nerve fiber layer surface, located away from the margins of large vessels, may provide the most dependable measurements of contour. These estimates of long-term variability of optic disk and peripapillary contour measurements provide clinically relevant confidence intervals with which to detect progressive glaucomatous nerve fiber damage.

Adult↗
PubMed1991

Phase II trial of whole-cell pertussis vaccine vs an acellular vaccine containing agglutinogens.

An acellular pertussis vaccine containing agglutinogens 2 and 3, pertussis toxin, and filamentous haemagglutinin was developed by the Centre for Applied Microbiology and Research in the UK. 188 infants were entered into a randomised blind trial and received either the acellular or a whole-cell vaccine, combined with diphtheria and tetanus toxoids, in a 3, 5, and 8-10 month schedule. Local reactions were similar in the two groups but significantly fewer infants had systemic symptoms after the acellular vaccine. Mean log-antibody titres to the agglutinogen and toxin components were higher with the acellular than with the whole-cell vaccine. Persistence of antibodies one year after the third dose was also better in the acellular group.

Antibodies, Bacterial↗
PubMed1991

Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans.

Oxidized low-density lipoprotein (LDL) is more atherogenic than native LDL. The initial step in the oxidation is the peroxidation of polyunsaturated fatty acids. Thus, decreasing the concentration of polyunsaturated fatty acids should reduce the susceptibility of LDL to oxidation. Therefore, we tested the possibility that diets enriched in oleate might result in LDL that is less susceptible to oxidative modification. LDL isolated from subjects consuming an oleate-enriched diet, compared with LDL from subjects on a linoleate-enriched diet, contained significantly more oleate (28.7% vs 11.5%) and less linoleate (31.9% vs 50.9%). Generation of conjugated dienes was significantly lower in the LDL from the oleate group. Most important, after incubation with endothelial cells, LDL from the oleate group underwent less degradation by macrophages. These studies demonstrate the feasibility of altering the diet in a way that will not raise LDL cholesterol concentrations and yet will decrease the susceptibility of LDL to oxidative modification.

Adult↗