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Biomedical subjects

G W Harrington

Publications and source records attributed to G W Harrington.

At least 19 recordsLinked to original sources

Torsional properties of the Canal Master instrument.

The torsional properties of a new type of endodontic hand instrument, the Canal Master, were compared with conventional machined K-type endodontic files. Sizes 20 through 50 were tested in clockwise (CW) and counterclockwise (CCW) directions. Canal Master instruments exhibited significantly less torque at yield and at failure in both the CW and CCW directions. Rotation at failure was significantly greater for the Canal Master instruments in both CW and CCW directions. There was no significant difference in either torque or the amount of rotation for the Canal Master instruments when comparing CW versus CCW rotation. There was no clinically visible evidence of deformation of the Canal Master instruments prior to torsional failure.

Dental Cavity Preparation

Midtreatment flare-ups.

It should be apparent that the prompt and effective treatment of midtreatment flare-ups of all types is an essential and integral part of the overall endodontic treatment procedure. The expeditious management of these flare-ups will do much to enhance a positive attitude among patients toward endodontic treatment and to ensure the well-being and comfort of these patients.

Dental Pulp Diseases

Estimation of the fraction of the dose of N-nitrosodimethylamine metabolized to methylamine in rats.

Despite many years of research on the metabolism of N-nitrosodimethylamine (NDMA) in rats, the significance of enzymatic denitrosation as a pathway remains unclear. To assess the role of this pathway of metabolism in rats, animals were administered NDMA by intravenous infusion at two infusion rates until steady state was achieved and the concentrations of NDMA (Css,NDMA) and methylamine (MA) (Css,MA), a product of the enzymatic denitrosation pathway, were determined in plasma. The clearance of NDMA (ClNDMA) from plasma was determined by dividing the infusion rate by Css,MA. The plasma clearance of MA (ClNDMA) was determined in a separate experiment. The fraction of the dose of NDMA metabolized by enzymatic denitrosation (fm) was calculated using the equation fm = (Css,MA*ClMA)/(Css,NDMA*ClNDMA). By this method it was estimated that 29% of the dose of NDMA was metabolized via the enzymatic denitrosation pathway. Thus enzymatic denitrosation is an important pathway in the metabolism of NDMA in rats.

Animals

A comparison of strains generated during placement of five endodontic posts.

Twenty-five extracted human maxillary central incisors were randomly divided into five equal groups. Crowns were removed 1 mm incisal to the cementoenamel junction. Endodontic treatment was carried out and each tooth was affixed with two strain gauges. The strain gauge wires were connected to a Wheatstone Bridge circuit. Each group of five teeth was restored with either a Para-Post Plus (the control post), Flexi-Post, Vlock post, Kurer Fin Lock Anchor, or a Radix Anchor. Strains generated during post placement were recorded and compared for the five groups using a one-way analysis of variance. The maximum strains accompanying placement of the Kurer Fin Lock Anchor and the Radix Anchor were significantly higher than those induced by placement of the other posts. Also, when the threaded posts were allowed to contact the bottom of the prepared channel, high strains resulted.

Analysis of Variance

Interspecies scaling of the pharmacokinetics of N-nitrosodimethylamine.

The pharmacokinetics of N-nitrosodimethylamine was studied in patas monkeys following i.v. doses of 0.5, 1.0, and 5.0 mg/kg and a p.o. dose of 1.0 mg/kg, and in Swiss mice at i.v. doses of 1.0 and 2.0 mg/kg. In the patas monkey the pharmacokinetics was linear over the i.v. dose range studied. The mean clearance (Cl), steady-state volume of distribution (Vss), mean residence time, and elimination half-life (t 1/2) were 103.3 +/- 26.7 (SD) ml/min, 3061 +/- 821 ml, 30.8 +/- 10.8 min, and 21.1 +/- 8.5 min, respectively. Assuming that the pharmacokinetics was linear at the p.o. dose used, the p.o. bioavailability of N-nitrosodimethylamine in the monkey was 49%. The pharmacokinetics was also linear in mice, and the average Cl, Vss, mean residence time, and t 1/2 were 3.81 ml/min, 21.0 ml, 5.5 min, and 11.9 min, respectively. These data and data for rats, hamsters, rabbits, dogs, and pigs taken from the literature were used to scale Cl and Vss to body weight using the allometric equation. The resulting equation for Cl was Cl = 49.7B0.998 and the equation for Vss was Vss = 748B1.05 where B is body weight in kg. The fit of the data to the equation was excellent in both cases. Using these equations and assuming a body weight of 70 kg for humans, the Cl and Vss for N-nitrosodimethylamine in humans are estimated to be 3450 ml/min and 64,800 ml, respectively.

Animals

Torsional properties of twisted and machined endodontic files.

The torsional properties of conventionally twisted K-type endodontic files and recently developed machined K-type endodontic files were compared. File sizes 10 through 40 were subjected to torsional load in clockwise and counterclockwise directions independently. Results showed that a statistically significant reduction in clockwise rotation occurred at failure with all of the machined files except size 10. Counterclockwise rotation at failure was also significantly lower for the machined files in sizes 10 through 30. There was no difference in torsional strength between the file types regardless of rotation direction. Therefore, machined files exhibit less ductility than twisted files prior to fracture and may be more susceptible to torsional failure clinically.

Dental Stress Analysis

An unusual ring contraction in the formation of N-nitrosohexamethyleneimine and N-nitrosopiperidine from tolazamide.

The previously reported reaction of tolazamide with nitrite, under physiological conditions, to form N-nitrosohexamethyleneimine and surprisingly, N-nitrosopiperidine was confirmed. By using the six-membered ring analogue of tolazamide, 1-(piperidyl)-3-(p-tolylsulfonyl)urea, which yields the corresponding N-nitrosopiperidine and N-nitrosopyrrolidine, the present study shows that an unusual ring contraction occurs, excising the carbon alpha to the nitrogen.

Carbon Radioisotopes

Comparison of three core buildup materials used in conjunction with two post systems in endodontically treated anterior teeth.

Fifty extracted maxillary central incisors with the crowns removed 1 mm coronal to the labial cementoenamel junction were endodontically treated. Post spaces were made 7 mm into the roots prior to cementing a 13-mm post with zinc phosphate cement. Twenty-five of the teeth were restored using a #6 (0.060-inch) Para-Post, and the remaining 25 teeth were restored with a #6 Para-Post Plus. Three core buildup materials, Ketac-Silver, Miracle Mix, and Tytin alloy were used in conjunction with the posts. Cast gold copings 10 mm in height with 1 mm collar on the root were cemented to the buildups. The teeth were loaded to failure at 130 degrees to the long axis of the root from the lingual with an Instron testing machine. The mean failure load of all of the teeth in this study was 21.6 kg. All of the teeth failed when the posts dislodged from the canals. The Para-Post Plus was not significantly more retentive than the Para-Post. No failures occurred within the buildup materials. No significant differences were demonstrated between the mean failure loads of the different buildup materials. Increased buccolingual root diameter, however, had a positive correlation (r = 0.46) with higher failure loads which was statistically significant (p less than 0.001).

Crowns

Inhibition of methylation of DNA by dimethylnitrosamine (DMN) in dehydroepiandrosterone-fed rats.

The influence of the anticarcinogen dehydroepiandrosterone (DHEA) on the metabolism and macromolecular interactions of the potent hepatocarcinogen dimethylnitrosamine (NDMA) was investigated. Male Sprague-Dawley rats (2-3 mo old) were fed DHEA for 14 d at a dietary level of 0.8%. Compared with pair-fed controls, the liver weights of the DHEA-treated animals increased significantly (11.7 vs. 7.1 g) with increases, per total liver, in proteins including those of cytosol and microsomes as well as cytochromes P-450 and b5. DNA content of the liver, however, remained constant. Five hours after a single ip dose of [14C]NDMA (30 mg/kg body wt, 42 microCi/rat) DNA methylation was reduced in the DHEA-fed animals as measured by 7-methyl- and O6-methylguanine per mole of guanine, by 39 and 31%, respectively. The rate of NDMA metabolism was slightly higher in the DHEA-fed rats as determined in vivo by the exhalation of 14CO2 and by the declining concentrations of NDMA in the blood. The incorporation of radioactivity from [14C]NDMA into hepatic proteins in vivo was greater (2.1-fold) in the DHEA-fed rats. Our results suggest that feeding rats with the adrenal steroid DHEA enhances the metabolic activation of NDMA in vivo, and that the increased association of NDMA-derived metabolites with increased hepatic cellular proteins may be partially responsible for protection of hepatic DNA from NDMA-induced damage.

Animals

Pharmacokinetics of N-nitrosodimethylamine in swine.

The pharmacokinetics of N-nitrosodimethylamine (NDMA) have been studied in swine. They were studied following i.v. administration of 0.1, 0.5 and 1.0 mg/kg, and following oral doses of 1.0 and 5.0 mg/kg of NDMA. Following a bolus i.v. dose, the concentration of NDMA in blood declined biphasically with a mean distribution half-life of 7 min and a mean elimination half-life of 28 min. The areas under the blood concentration versus time curves (AUC) were roughly proportional to dose indicating that the pharmacokinetics in this dose range were first order. The mean systemic clearance from blood was 65.8 ml/min/kg, the steady-state volume of distribution was 1.4 l/kg, and the mean residence time was 20 min. Following the oral doses, the AUC and peak concentration in blood were not proportional to the dose. It is likely that the pharmacokinetics at the lower dose were first order, but at the higher dose the pharmacokinetics were no longer first order because metabolism was saturated. The bioavailability of the 1.0 mg/kg dose was 67%. Since the clearance was probably due to metabolism and the clearance from blood exceeded hepatic blood flow, the high bioavailability suggests that extrahepatic metabolism plays an important role in the systemic clearance of NDMA in swine.

Animals

Pharmacokinetics of N-nitrosodimethylamine in beagles.

The pharmacokinetics of N-nitrosodimethylamine (NDMA) has been studied in beagles. Four male beagles were given 0.5- and 1.0-mg/kg doses of NDMA i.v. and 1.0- and 5.0-mg/kg doses p.o., and at appropriate times after dosing blood samples were drawn and the concentration of NDMA was measured. The experiments were separated by at least 1 week. Following a bolus i.v. dose, the concentration of NDMA in blood declined biphasically with a mean distribution half-life of 19 min and a mean elimination half-life of 73 min. The areas under the blood concentration versus time curves were proportional to the dose indicating that the pharmacokinetics in this dose range were first order. The mean systemic clearance was 43.3 ml/min/kg, the volume of distribution at steady state was 1.9 liters/kg and the mean residence time was 45 min. The clearance of NDMA in the dog was entirely metabolic because no NDMA could be detected in urine after i.v. dosing. The areas under the curve and maximum concentration in blood after the two p.o. doses were not proportional to dose. The evidence suggests that the pharmacokinetics of the 1.0-mg/kg dose were first order, but at the 5.0-mg/kg dose the metabolism of NDMA was saturated. The bioavailability of the lower p.o. dose (i.e., the fraction of the dose that reached the systemic circulation) averaged 93%. The high bioavailability was unexpected since, in the rat, the bioavailability of NDMA is only about 10%, and the systemic clearance in the dog exceeds hepatic blood flow. These data suggest that a substantial fraction of the systemic clearance is extrahepatic and that the pharmacokinetics of NDMA in higher species may be quite different from that observed in rodents.

Administration, Oral

A comparison of three restorative techniques for endodontically treated anterior teeth.

An in vitro study of 45 teeth compared the failure loads of endodontically treated teeth restored with pin and amalgams, Para-Post dowel and composite, and glass ionomer/amalgam alloy coronal-radicular buildups. The following conclusions were made. The Para-Post and composite buildups exhibited the highest mean failure load, 35.3 kg. The mean failure load for pin and amalgam buildups was 27.9 kg. Glass ionomer/amalgam alloy coronal-radicular buildups exhibited the lowest mean failure load, 14.1 kg. Restoration of endodontically treated anterior teeth with glass ionomer/amalgam alloy coronal-radicular buildups is contraindicated.

Crowns

Surgical procedure for chronic biliary sample collection in pigs.

To collect biliary samples from pigs, catheters were placed in the distal end of the gallbladders in twelve 20- to 30-kg pigs. An occluder cuff was placed around the bile duct proximal to the duodenum. Inflation of the occluder cuff prevented bile flow into the duodenum and allowed total collection of bile from the catheter in the gallbladder. Deflation of the occluder cuff allowed return of bile flow into the duodenum. Two pigs developed gastric ulcers and two pigs had bile duct dilatation. These responses were attributed to occluder cuffs of inadequate size which could have caused partial or complete obstruction of the bile duct.

Animals

The pig as an animal model for the study of nitrosamine metabolism.

Surgical procedures have been developed that permit the sampling of portal blood, bile and hepatic blood in intact pigs. Animals so prepared have been used to study liver metabolism and biliary excretion of N-nitrosodimethylamine (NDMA) following oral and intravenous dosing.

Animals

Formation of an N-nitrosamine by oxidation.

Tolazamide, an antidiabetic drug, was found to produce N-nitrosohexamethyleneimine (NHM) upon exposure to an oxidizing agent and in the absence of a nitrosating agent. The oxidizing agents were either hydrogen peroxide or oxygen.

Carcinogens

The metabolism of N-nitrosomethylaniline.

The distribution in the body, rate of disappearance from organs, tissues, and blood, and excretion in the urine of N-nitrosomethylaniline (NMA, N-nitrosophenylmethylamine) was investigated after various single doses given IP to rats. The compound was distributed fairly evenly throughout the body with no preferential concentration in the esophagus, its target organ for carcinogenicity. The high lipid solubility of NMA did not lead to any increased accumulation in adipose tissue. According to its rate of disappearance from circulating blood and tissues of rats, and from the whole bodies of mice after injection, NMA appeared to be rapidly metabolized. Methylaniline (MA), the parent amine, was found in the urine after administration of NMA but the amounts present were small relative to the dose of NMA. Administered MA was mainly excreted unchanged in the urine, suggesting that denitrosation of NMA could only be a minor metabolic pathway. No volatile nitrosamines were found in the urine or blood of rats given NMA, indicating that little, if any, transnitrosation could have occurred to yield these compounds.

Aniline Compounds