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Biomedical subjects

C R Clark

Publications and source records attributed to C R Clark.

At least 181 records · Page 10Linked to original sources
PubMed1985

Binding of warfarin by human albumin in the presence of a perfluorochemical blood substitute.

The effect of a perfluorochemical blood substitute on ligand binding by human albumin was examined using warfarin as a model drug. Binding of warfarin by four per cent human albumin solutions diluted with either buffer or blood substitute, and by blood substitute diluted with buffer was examined. Solutions containing 2 or 10 micrograms/ml warfarin were quantitated by liquid scintillation counting using 14C-warfarin. The per cent warfarin free at room temperature was determined by centrifugation followed by supernatant ultrafiltration. Warfarin was weakly bound by the blood substitute and the overall effect of albumin dilution with the blood substitute was an increase in per cent warfarin free. Blood substitute binding of warfarin may explain the decrease of per cent warfarin free observed when albumin solutions were diluted to 50 and 75% v/v with blood substitute rather than buffer. However, the per cent warfarin free increased when albumin solutions were diluted to 25% v/v with blood substitute rather than buffer. The fraction free increased by 39.0% and 30.4% at total warfarin concentrations of 2 and 10 micrograms/ml, respectively. This relative increase in per cent warfarin free may be the result of a direct and/or indirect displacement of albumin bound warfarin by a component(s) of the blood substitute.

Blood Substitutes↗
PubMed1985

Fractures of the dens. A multicenter study.

The treatment of fractures of the dens is often inadequate, and surgeons are divided in their opinions regarding the best surgical management of these potentially serious injuries. Because of these concerns, the Cervical Spine Research Society conducted a multicenter survey of its membership regarding the management of these fractures. Fractures of the dens can be effectively classified according to the anatomical level of the fracture, as described by Anderson and d'Alonzo. We have found that the degree of angulation and amount of displacement are also important factors. Fractures occurring at the junction of the dens with the vertebral body (Type-II fractures) were found to be the most troublesome. The initial management of these fractures with a halo device was successful in only 68 per cent; however, posterior cervical fusion was successful in 96 per cent, and that appears to be the treatment of choice. Fractures extending into the vertebral body (Type-III injuries) were found not to be as benign as has been reported. Malunion and non-union occurred in patients with this injury who were treated with an orthosis alone, and a halo device or surgery may be indicated for unstable lesions.

Adult↗
PubMed1984

A comparison of genotoxicity of automotive exhaust particles from laboratory and environmental sources.

This research (1) ranked the genotoxicity of methylene chloride extracts of laboratory and environmentally collected particles and (2) evaluated the role of collection location and sample composition on genotoxic potency. Samples of exhaust from a spark-ignition automobile, light-duty diesel automobile, and a heavy-duty diesel engine operated in a laboratory on a dynamometer were studied, as well as samples taken in a highway tunnel and outside the same tunnel. The tunnel samples were collected 30 m inside or 56 m outside the exit portal at times when between 70%-95% of the traffic consisted of diesel trucks. In the Ames Salmonella mutagenicity assay, each extract produced a dose-dependent increase in mutagenicity in strain TA-98 without addition of liver S-9 fraction. Extracts from two tunnel samples collected 1 yr apart, and extracts of particles collected outside the tunnel had similar mutagenic activity. The order of mutagenic activity per microgram of extract in TA-98 without S-9 from the lowest to the highest was environmental sample less than or equal to tunnel less than heavy-duty diesel less than light-duty diesel less than spark ignition. Addition of S-9 or testing in Salmonella strains resistant to the mutagenicity of nitroaromatic compounds (TA-98 NR and TA-98 1,8-DNP6) decreased the mutagenic response. With cell killing, sister chromatid exchanges, and mutations as endpoints in Chinese hamster ovary cells (CHO), the order of potency was tunnel less than light-duty less than spark-ignition samples. All three extracts induced a similar amount of mitotic delay per microgram with or without S-9. Enhanced chromosome aberration frequency was detected only in cells exposed to extracts from spark-ignition exhaust. The data indicated that genotoxic activity was detected in each particle extract, that the potency ranking was similar using different genetic endpoints, and that the magnitude of the genotoxic potency was similar.

Air Pollutants↗
PubMed1984

Toxicological and chemical characterization of the process stream materials and gas combustion products of an experimental low-btu coal gasifier.

The process gas stream of an experimental pressurized McDowell-Wellman stirred-bed low-Btu coal gasifier, and combustion products of the clean gas were characterized as to their mutagenic properties and chemical composition. Samples of aerosol droplets condensed from the gas were obtained at selected positions along the process stream using a condenser train. Mutagenicity was assessed using the Ames Salmonella mammalian microsome mutagenicity assay (TA98, with and without rat liver S9). All materials required metabolic activation to be mutagenic. Droplets condensed from gas had a specific mutagenicity of 6.7 revertants/microgram (50,000 revertants/liter of raw gas). Methylnaphthalene, phenanthrene, chrysene, and nitrogen-containing compounds were positively identified in a highly mutagenic fraction of raw gas condensate. While gas cleanup by the humidifier-tar trap system and Venturi scrubber led to only a small reduction in specific mutagenicity of the cooled process stream material (4.1 revertants/microgram), a significant overall reduction in mutagenicity was achieved (to 2200 revertants/liter) due to a substantial reduction in the concentration of material in the gas. By the end of gas cleanup, gas condensates had no detectable mutagenic activity. Condensates of combustion product gas, which contained several polycyclic aromatic compounds, had a specific mutagenicity of 1.1 revertants/microgram (4.0 revertants/liter). Results indicate that the process stream material is potentially toxic and that care should be taken to limit exposure of workers to the condensed tars during gasifier maintenance and repair and to the aerosolized tars emitted in fugitive emissions. Health risks to the general population resulting from exposure to gas combustion products are expected to be minimal.

Air Pollutants↗
PubMed1984

An in-vitro study of the kinematics of the normal, injured and stabilized cervical spine.

The relative motion between various vertebrae of multi-level cervical ligamentous spinal segments (C2-T2), using Bryant angles, is described. A three-dimensional sonic digitizer was utilized to study the motion in flexion, extension, right lateral bending and right axial rotation. Effects of a number of injuries and stabilization (interspinous wiring and acrylic cement, PMMA) on the motion behavior of C5-C6 (injured) and C4-C5 (superior to injured) levels were investigated. The data were normalized with respect to intact specimens. The injury to capsular ligaments at C5-C6 produced a significant increase in the relative motion at C4-C5. Although the interspinous wiring reduced the motion at C5-C6 the C4-C5 motion was still higher. The application of PMMA made the motion at C4-C5 comparable to the intact specimen.

Adult↗
PubMed1984

Anticonvulsant activity of some 4-aminobenzamides.

A series of 4- aminobenzamides of some simple primary and secondary amines were prepared and evaluated for anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole ( metrazole ) and in the rotorod assay for neurologic deficit. For those N-alkyl amides tested, 4-amino-N- amylbenzamide (6) was the most potent against maximal electroshock seizures (MES): ED50 = 42.98 mg/kg; however, the N- cyclohexylbenzamide (8) showed the greatest protective index (PI = TD50/ED50), 2.8. The introduction of a second aromatic ring produced more potent compounds, with d,l-4-amino-N-(alpha-methylbenzyl)-benzamide (12) showing the highest level of activity. This compound has an anti-MES ED50 of 18.02 mg/kg in mice when administered intraperitoneally (ip) and a TD50 of 170.78 mg/kg (PI = 9.5) in the same species. These data compare quite favorably with those for phenobarbital and phenytoin in the same assays.

Animals↗
PubMed1984

Methylmethacrylate stabilization of the cervical spine.

Several conditions that lead to instability of the cervical spine require surgical fixation, and on occasion that procedure may include the use of methylmethacrylate. In the series that we are reporting, there were eighteen patients with malignant disease, seventeen with fractures, twelve with rheumatoid arthritis, and five with osteoarthritis. In the survivors, a four-year follow-up showed excellent relief of instability and no complications attributable to the methacrylate except for one fracture of the methacrylate that did not produce symptoms.

Adult↗
PubMed1983

Comparative mutagenicity of a coal combustion fly ash extract in Salmonella typhimurium and Chinese hamster ovary cells.

The dichloromethane extract of a coal combustion fly ash sample obtained from an experimental fluidized bed coal combustor was tested for mutagenicity in Salmonella typhimurium and cultured Chinese hamster ovary (CHO) cells. The extract was directly mutagenic in S typhimurium strain TA98 and the nitroreductase deficient strains TA98NR and TA98/1,8DNP6. The mutagenicity observed in TA98NR and TA98/1,8DNP6 was lower than that in TA98. Addition of exogenous Aroclor 1254-induced rat liver supernatant (liver S9) decreased the bacterial mutagenicity of the extract. A different mutagenic response was observed in CHO cells. In the absence of liver S9, although the extract was cytotoxic to CHO cells, no significant mutagenicity was observed. Addition of exogenous liver S9 decreased the cytotoxicity and increased the mutagenicity at both Na+-K+-ATPase and hypoxanthine-guanine phosphoribosyl transferase (HGPRT) gene loci in CHO cells. Using gas chromatography/mass spectrometry (GC/MS) and tandem quadruple mass spectrometry, a number of polynuclear aromatic hydrocarbons (PAHs) and nitrated PAHs (nitro-PAHs) were tentatively identified and quantitated. A possible explanation of the difference in bacterial and mammalian mutagenicity of the extract is that the bacterial mutagenicity was induced by the nitro-PAHs that are potent bacterial mutagens and mammalian mutagenicity was induced by both PAHs and nitro-PAHs that are promutagens.

Animals↗
PubMed1983

Effects of clenbuterol hydrochloride on certain respiratory and cardiovascular parameters in horses performing treadmill exercise.

Five standardbred geldings received intravenous clenbuterol hydrochloride and saline in a crossover experiment to evaluate the effects of clenbuterol on certain cardiorespiratory parameters during and after treadmill exercise. The exercise test consisted of four steps. Step 1 at a speed of 76 m per minute, step 2 at 129 m per minute, step 3 at 190 m per minute and step 4 at 236 m per minute. The duration of each step was two minutes, except step 4 which was four minutes. The treadmill was set at a grade of 19 per cent. Before exercise, 30 minutes after clenbuterol or saline administration, arterial and mixed venous blood gases, mean arterial pressure, mean pulmonary artery pressure, telemetric electrocardiogram and respiratory rate were measured. The measurements were repeated immediately before completion of step 2, step 4 and after one minute, 10 minutes and 30 minutes of recovery from exercise. After clenbuterol administration there was a transient fall in mean arterial pressure, which had returned to control values by 90 seconds. There was no change in mean pulmonary artery pressure. During exercise the heart rate was significantly higher at the end of steps 1 and 4 and after 10 minutes recovery when horses given clenbuterol were compared with those given saline. No adverse effects on the electrocardiogram were demonstrated. Effects of clenbuterol on blood gases included an increase in PaO2 and decrease in PaCO2 one minute after exercise, when compared to saline. It was concluded from the parameters examined that there was no evidence that clenbuterol had any significant untoward effect on the circulatory system of exercising horses.

Animals↗
PubMed1983

Liquid chromatographic analysis of samples containing cocaine, local anesthetics, and other amines.

A liquid chromatographic procedure is described for the separation of cocaine, local anesthetics, and other amines often encountered in cocaine look-alike preparations. Amines such as ephedrine, pseudoephedrine, and phenylpropanolamine are identified following derivatization with phenylisothiocyanate. The isocratic, reverse phase method uses dual wavelength detection at 254 and 280 nm.

Amines↗
PubMed1982

MS/MS analysis of diesel emissions and fuels treated with NO2.

Correlations between direct-acting mutagens in diesel emissions and the activity of nitroaromatic compounds have been noted, but detection and identification of nitro-compounds in diesel particulates has remained an elusive problem. In the results reported here, MS/MS (tandem mass spectrometry) was found to detect nitroaromatic compounds in fractionated and unfractionated diesel soot extracts. The nitro-compounds detected ranged from two- to four-ring polynuclear aromatic hydrocarbon derivatives and were primarily mono-nitro derivatives. An aromatic fraction from diesel fuel reacted with NO2 resembled diesel exhaust extracts from an engine operating on the same fuel. Therefore, it is possible that nitroaromatic derivatives in diesel exhaust may be in part due to unburned fuel residues reacting with NO chi formed in the combustion process. The utility of MS/MS in comparing complex mixtures from different sources or subfractions thereof is discussed.

Fuel Oils↗