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Biomedical subjects

M G Cote

Publications and source records attributed to M G Cote.

7 recordsLinked to original sources
PubMed1995

Sestamibi parathyroid imaging.

Since the introduction of technetium-99m (99mTc) sestamibi (hexakis-2-methoxyisobutyl isonitrile) as a parathyroid imaging agent in 1989, many investigators using several different imaging protocols have reported uniformly excellent results for localization of parathyroid adenomas. Exact localization of hyperplastic parathyroid glands has not met with as much success. However, the results of multiple comparative studies suggest that the diagnostic utility of sestamibi protocols equals or exceeds other noninvasive, nonscintigraphic imaging strategies, including high-resolution ultrasound, computed tomography, and magnetic resonance imaging. Two different, but not necessarily mutually exclusive imaging strategies have been used: subtraction imaging using iodine-123 (123I) or 99mTc sodium pertechnetate as the thyroid agent, and sestamibi dual-phase imaging, which takes advantage of differential washout of sestamibi from thyroid and parathyroid tissue. Sestamibi subtraction imaging has been shown to have greater sensitivity for abnormal parathyroid glands compared with thallium-201 subtraction imaging using pooled data, 87% versus 71%, respectively. Dual-phase sestamibi imaging protocols are much more variable in their conduct and have a much greater variability in sensitivity, 43% to 91%, but with a pooled sensitivity of 73%. Data suggest that dual phase techniques are at least as sensitive, and in optimized protocols, superior to, thallium-201 subtraction techniques. This superiority is attributed to the favorable washout kinetics of sestamibi and the superior imaging characteristics of the 99mTc label. Specificity and positive predictive value for both sestamibi techniques are very high, typically greater than 90% and at least equal to thallium-subtraction protocols, although specificity may be slightly lower for sestamibi subtraction techniques. Therefore, sestamibi protocols are the scintigraphic procedure of choice for parathyroid imaging. Dual-phase sestamibi protocols are more robust and lend themselves to single photon emission computer tomography (SPECT) imaging, and may be followed sequentially by subtraction techniques if results are inconclusive. Despite the excellent results of sestamibi parathyroid imaging, it is unclear whether this accuracy can compete with the even better success of an experienced surgeon in initial surgeries for hyperparathyroidism, and routine preoperative imaging before initial surgery is still controversial. However, sestamibi parathyroid imaging is an excellent addition to a correlative imaging approach in reoperations for persistent and recurrent hyperparathyroidism.

Adenoma↗
PubMed1989

Effect of cimetidine on hepatic biochemical changes, liver toxicity and major urinary metabolite excretion of trichloroethylene in rats.

The effects of cimetidine (CIM) (an inhibitor of the hepatic microsomal monooxygenase system) on the metabolism and hepatotoxicity of trichloroethylene (TRI) were studied in male Sprague-Dawley rats. Rats were given three doses of 120 mg/kg i.p. (low-dose regimen) of CIM at 0, 6 and 11 h for 1 day, or ten doses of 200 mg/kg (high-dose regimen) at 8, 11, 14 and 17 h for 2 days and 8 and 11 h on 3rd day. Trichloroethylene (0.5 or 0.65 ml/kg) was administered i.p. 1 h after 2nd dose (low-dose regimen) or 9th dose (high-dose regimen) of CIM. In the low-dose regimen study, the activity of hepatic microsomal aminopyrine N-demethylase was decreased 1 and 5 h after the second dose and 7 h after the third dose of CIM, but became normal 20 h after the last dose. The cytochrome P-450 content and the activities of aniline hydroxylase and epoxide hydratase remained unchanged. Trichloroethylene at both dose levels produced liver toxicity, as verified by increase in activities of SDH and SGPT as well as by liver histology. Cimetidine alone had no such effect. An apparent reduction in TRI toxicity by CIM (at both dose regimens) could be observed histologically. The biochemical tests (SDH and SGPT) corroborated the histological changes only when TRI was given at a dose of 0.5 ml/kg combined with a high-dose regimen of CIM. Cimetidine at both dose regimens had a tendency to decrease the in vivo metabolism of TRI.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine Transaminase↗
PubMed1985

Absence of genotoxic effects of nonasbestos mineral fibers.

The biological activity of natural and synthetic mineral fibers has been examined. Natural attapulgite [(Mg, Al)2Si4O10(OH).4H2O], synthetic xonotlite [Ca3Si3O8(OH)2] and natural sepiolite [Mg2Si3O8.2H2O] were selected. Genotoxic effects were investigated by means of a well established cellular model based upon the measurement of unscheduled DNA synthesis (UDS) in rat hepatocytes in primary culture. The intrinsic capacity of the fibers (1 and 10 micrograms/ml) to induce UDS was first tested. None of the fiber types showed detectable UDS-eliciting activity. Also, the possible modulation of the cellular response to genotoxic agents by the materials was examined by exposing the cells to mixtures of 2-acetylaminofluorene (AAF) (0.05 and 0.25 micrograms/ml) and fibers (1 and 10 micrograms/ml). In these experiments, the UDS response was significantly diminished in the presence of xonotlite. This phenomenon may reflect changes in the uptake and/or metabolism of AAF or may result from an inhibition of DNA repair processes, the latter suggesting a possible cocarcinogenic potential for this synthetic silicate. These results point to the immediate necessity of studying more extensively the biological effects of fibrous materials that can be used as substitutes for asbestos.

Animals↗
PubMed1985

Ultrastructural study of mineral fiber uptake by hepatocytes in vitro.

Cellular interactions of a series of fibrous materials were examined by the use of a well established in vitro system. Primary cultures of hepatocytes were exposed to natural attapulgite, synthetic xonotlite and natural sepiolite. Ultrastructural analyses revealed that hepatocytes can engage in the phagocytosis of all 3 types of fibers over an exposure period of 20 h. Attapulgite fibers were found in plasma membrane invaginations, and deeper in the cytoplasm, in vesicles exhibiting various shapes. Xonotlite was also incorporated in plasma membrane invaginations; furthermore, these fibers were present in large vacuoles where they were circumscribed by membranes and appeared somewhat isolated from the cytoplasm. Sepiolite fibers were also taken up by the cells and could likewise be identified in the previously described structures. These observations point to the relevance of the hepatocyte model for investigating the effects of fibrous materials at the cellular level.

Animals↗
PubMed1985

Genotoxicity of dimethylnitrosamine in the presence of chrysotile asbestos UICC B and xonotlite.

Interactions of particulates with chemical genotoxic agents may play an important role in the induction of carcinogenesis. With respect to bronchogenic cancer, the synergism associated with combined exposure to asbestos and tobacco smoke is a well-documented phenomenon. The present work focused on chrysotile asbestos and xonotlite. The latter is a fibrous calcium silicate which is increasingly being used to replace asbestos in various industrial applications. The study was aimed at testing the possible interaction of these materials with dimethylnitrosamine (DMN), a genotoxic component of tobacco smoke. The capacity of fibers to interfere with the genotoxic response elicited by DMN in the UDS/hepatocyte assay system specifically designed for sensitive detection of short-patch DNA repair, was looked for. The properties of the selected fibers with respect to binding affinity towards DMN were also examined.

2-Acetylaminofluorene↗
PubMed1977

Lung injury induced by butylated hydroxytoluene: cytodynamic and biochemical studies in mice.

Butylated hydroxytoluene, a common food additive, is known to produce proliferative pulmonary changes characterized by increased DNA, RNA, and lung weight. In the present study, reactive hyperplasia and fibrosis were produced within 9 days after a single intraperitoneal injection of 400 mg. per kg. of butylated hydroxytoluene was given to mice. Initial perivascular edema with cell infiltrates was followed by necrosis of type 1 alveolar epithelial cells and by division of type 2 cells which repopulated the alveolar wall with unusually large epithelial cells containing abundant cytoplasm. DNA synthesis, as indexed by thymidine and uridine kinase levels and by 3H-thymidine uptake, increased at 2 days, peaked at 4 days, and dropped gradually to near normal by day 9. Differential counts of labeled cells revealed that the early rise was due to epithelial cell proliferation; in turn, interstitial and endothelial cells entered the proliferative phase. Endothelial labeling peaked at day 6 immediately following ultrastructural evidence of endothelial injury. It is concluded that the proliferative pulmonary changes that occur after the administration of butylated hydroxytoluene are a consequence of cell injury and necrosis. The reparative processes occur predominantly at the alveolar epithelium and interstitium with the production of fibrosis. The cellular hypertrophy and hyperplasia observed in this study account for the biochemical changes in pulmonary RNA and DNA that have been described previously.

Animals↗