Biomedical subjects

C R Clark

Publications and source records attributed to C R Clark.

At least 91 records · Page 5Linked to original sources

PubMed1992

Radiologic evaluation of dens fracture. Role of plain radiography and tomography.

A retrospective study of 50 dens fractures was performed. In 47 of 50 cases (94%), plain radiographs disclosed the fracture. Initial cross-table lateral view alone showed the fracture in 43 cases. In the remaining four cases, routine plain films revealed the fracture: open-mouth view in three cases and lateral skull view in one case. In 3 of 50 cases (6%), plain films were negative, and fractures were seen only on tomography. Conventional circular tomography was performed in 26 cases; results were divided into 3 categories according to the significance of the findings: Category I, tomography confirmed plain radiographic findings, but added no further information; Category II, tomography detected additional findings or showed the extent of injury better than plain radiography; Category III, fracture was only seen by tomography. There were 19 cases in Category I, 4 in Category II, and 3 in Category III. Careful evaluation of plain radiographs remains the primary method for diagnosis of dens fractures. Tomography should be performed whenever plain radiographs or clinical symptoms are suspicious for dens fracture. In addition, tomography is useful to define the fracture level and pattern, which are important factors in the management of these injuries.

Cervical Vertebrae↗

PubMed1992

HI-6 pharmacokinetics in rabbits after intravenous and intramuscular administration.

The pharmacokinetics of HI-6 ((4-carboxamidopyridinium (1) methyl)-(2'-hydroxyiminomethyl-pyridinium (1') methyl) ether dichloride) have been studied in rabbits receiving an intramuscular (50 micrograms kg-1) or intravenous (12.5 micrograms kg-1) dose. The plasma concentration-time profile for the intramuscular dose (n = 8) fits a one-compartment open model with first-order absorption and elimination. The absorption half-life was 2 min and maximum concentration (51 micrograms mL-1) was reached in 9 min. The pharmacokinetics for the intravenous dose (n = 8) was described by a two-compartment open model with first-order distribution and elimination. The apparent volume of distribution was 0.1 L kg-1. Half-lives of distribution and elimination were 5 and 38 min, respectively. The results indicate HI-6 is rapidly absorbed, distributed and eliminated in rabbits receiving an intramuscular dose.

Animals↗

PubMed1991

An appraisal of polystyrene-(ELISA) and nitrocellulose-based (ELIFA) enzyme immunoassay systems using monoclonal antibodies reactive toward antigenically distinct forms of human C-reactive protein.

The purpose of this study was to compare and contrast two enzyme immunoassay systems: the enzyme-linked immunosorbent assay (ELISA), which utilizes polystyrene microtiter plates as the adsorptive surface and the enzyme-linked immunoflow assay (ELIFA), which utilizes nitrocellulose membranes. The principal parameter under scrutiny was the denaturing or unfolding effects caused by the interaction of the protein with the adsorptive surfaces in each assay system. These effects were monitored by utilizing two conformationally distinct forms of human C-reactive protein (CRP), the native form of CRP and a denatured form (M-CRP), with a corresponding panel of monoclonal antibodies (MAbs) specific to either CRP or M-CRP. The results show that the ELIFA system was less sensitive than the ELISA system but that the ELIFA assay can be completed in less time than the ELISA. Also, adsorption of native CRP to the polystyrene surface in the ELISA system resulted in conformational changes of the adsorbed native CRP protein such that M-CRP reactive determinants were available for binding with anti-M-CRP MAbs, whereas native CRP adsorbed to the nitrocellulose membrane in the ELIFA system resulted in very limited conversion of CRP to M-CRP reactive epitopes. These results have important implications for development of immunoassays and screening of MAbs for proteins whose conformations may be affected by adsorption to various surfaces.

Antibodies, Monoclonal↗

PubMed1991

Bone-particle-impregnated bone cement: an in vivo weight-bearing study.

To evaluate an experimental inorganic-bone-particle-impregnated bone cement, canine hip prostheses were implanted in dogs using a regular bone cement on one side and the experimental bone cement on the other. In a preliminary feasibility study, bone ingrowth into the resorbed bone-particle spaces was established 3 months after implantation in three dogs. In a more detailed study, twenty-eight (28) dogs were divided in four groups to delineate the effects of time on the phenomena of bony ingrowth. One month after implantation, active bone ingrowth into the bone cement was obvious. By 3 months postimplantation, the ingrowth appeared to have traversed the thickness of the bone-particle-impregnated cement. By the fifth month, most of the interconnected inorganic bone particles were replaced by new bone. At the end of a year, the ingrown bone was mature and negligible new bone activity was present. Biomechanical pushout tests closely corroborated the histologic observations. The maximum shear strength of the cement/bone interface of the experimental side reached 3.6 times that of the control side at 5 months postimplantation. No further improvements were seen at 12 months postimplantation. A viable bone/cement interface may result in a better orthopedic implant fixation system by combining the advantages of both cement for immediate rigidity and biological ingrowth for longterm stability.

Animals↗

PubMed1991

Interhemispheric differences in the planning and execution of sequences of skilled finger movements.

An index-middle finger (double) tapping task was used to examine hemispheric differences in the planning and execution of skilled finger movements. In two experiments, subjects responded to a simple cue presented tachistoscopically in the left or right visual field, by performing a predetermined number of double taps, (between one and eight inclusive), with either the left or right hand. Reaction times (RT) increased linearly as a function of increasing number of taps, when response sequences were controlled by the left hemisphere. In contrast, an inverse quadratic trend was obtained with right hemisphere control. When both hemispheres were involved in the stimulus-response sequence, the latency function incorporated elements of both trends, suggesting interaction between the hemispheres. The RT trends reflect differences in motor planning between the hemispheres. The conditions engaging only the right or left hemispheres did not differ in motor execution, as measured by tapping duration, variability or errors. However, when both hemispheres were involved there was evidence of interaction, which was evident as interference when the right visual field or left hemisphere was cued but the motor response was under the control of the right hemisphere (left hand). Overall, the results indicate that hand differences in fine motor skill may be determined by hemispheric differences associated with motor preparation rather than response execution.

Adolescent↗

PubMed1991

Niacinamide pretreatment reduces microvesicle formation in hairless guinea pigs cutaneously exposed to sulfur mustard.

It has been proposed that sulfur mustard (HD) may indirectly activate poly(ADP-ribose) polymerase (PADPRP) by alkylating cellular DNA (Papirmeister et al., 1985). Activation of PADPRP results in the depletion of cellular NAD+, which initiates a series of biochemical processes that have been proposed to culminate in blister formation. Preventing PADPRP activation and NAD+ depletion should inhibit blister formation. Niacinamide is both an inhibitor of PADPRP and a precursor for NAD+ synthesis. The present study was undertaken to determine whether niacinamide can protect against HD-induced microvesication in cutaneously exposed hairless guinea pigs. Each site was exposed to HD for 8 min by means of a vapor cup. Niacinamide (750 mg/kg, ip) given as a 30-min pretreatment inhibited microvesicle formation by 50% after HD application. However, niacinamide given 2 hr after HD application did not reduce microvesicle formation. There was no benefit when niacinamide was given as both a pretreatment and treatment when compared to niacinamide given only as a pretreatment. The reduction in microvesication 24 hr after HD did not correlate with skin NAD+ content. Niacinamide did not reduce the degree of erythema or edema. Ballooning degeneration of basal epidermal cells was present in some niacinamide pretreated HD exposure sites. These results suggest that niacinamide may only be effective as a pretreatment compound to reduce the incidence of HD-induced microvesicle formation. Maintenance of skin NAD+ content may not be solely responsible for inhibiting microvesicle formation and inhibition of PADPRP may be of greater importance.

Animals↗

PubMed1991

Methods for the analysis of 1-(3,4-methylenedioxyphenyl)-2-butanamine and N-methyl-1-(3,4-methylenedioxyphenyl)-2-propanamine (MDMA).

The infrared and mass spectra of N-methyl-1-(3,4-methylenedioxyphenyl)-2-propanamine (MDMA) and 1-(3,4-methylenedioxyphenyl)-2-butanamine are quite similar. These two compounds differ only in the position of substitution of a single methyl group. MDMA is a controlled street drug known as Ecstasy, while the isomeric butanamine is a member of a new class of potential psychotherapeutic agents called entactogens. These two compounds produce similar mass spectral fragmentation patterns including a common base peak at m/z 58. Reversed-phase liquid chromatographic (RPLC) methods consisting of a C18 stationary phase and an aqueous scidic mobile phase were used to separate these two compounds. Thus, LC methods can be used to differentiate MDMA from the isomeric butanamine for forensic analysis.

3,4-Methylenedioxyamphetamine↗

PubMed1990

Anticonvulsant activity of some 4-methoxy- and 4-chlorobenzanilides.

A series of mono-, di-, and trimethylated derivatives of 4-chloro- and 4-methoxybenzanilide was synthesized and evaluated for anticonvulsant activity. This series was prepared in the course of studies designed to examine the relationship between anticonvulsant effects and benzamide structure. The compounds were tested in mice against seizures induced by maximal electroshock (MES) and pentylenetetrazole (scMet), as well as with the rotorod assay for neurologic deficit. In mice dosed intraperitoneally, 4-methoxy-2, 6-dimethylbenzanilide (4) showed a median anticonvulsant potency (ED50) of 18.58 mg/kg in the MES test and a median toxicity (TD50) of 133.72 mg/kg in the rotorod toxicity assay, yielding a protective index (PI = TD50/ED50) of 7.2. In mice dosed orally with 4, the anti-MES ED50 was 27.40 mg/kg and the TD50 dose was determined to be 342.58 mg/kg, resulting in a protective index of 12.5.

Anilides↗

PubMed1990

Pharmacokinetics of physostigmine intramuscularly administered to guinea pigs.

Physostigmine pharmacokinetics was determined in guinea pigs following im administration of 5-146 micrograms/kg. Eighteen male guinea pigs were divided into three equal groups and given dosages of 5, 27, and 146 micrograms/kg, respectively. Physostigmine was given in the right hind limb and blood samples were collected at various times up to 300 min postinjection via an indwelling carotid catheter. Unbound physostigmine plasma concentrations were analyzed by HPLC. The concentration-time profile for each animal was fitted to standard pharmacokinetic models. A one-compartment open model with first-order absorption and elimination provided the best fit. For all dosage groups, physostigmine concentrations peaked in approximately 30 min. Apparent volumes of distribution (assuming 100% bioavailability) ranged from 1.9 to 2.2 L/kg. Systemic clearances and elimination half-lives were 30-36 mL/min/kg and 40-50 min, respectively. The area under the concentration-time curve and the Cmax were linearly related to the dose, indicating pharmacokinetic linearity. In conclusion, physostigmine, intramuscularly administered to the guinea pig, is absorbed, distributed, and eliminated rapidly, and the pharmacokinetics behave linearly within the 5-146-micrograms/kg dosage range.

Animals↗

PubMed1990

Event-related potentials and monoamines in autistic children on a clinical trial of fenfluramine.

In a double blind, crossover study of the response of autistic subjects to fenfluramine, event-related potentials (ERPs) were recorded from 7 subjects on an attention-demanding auditory choice reaction time task (ACRT). ACRT, IQ and biochemical measures were taken after 5 months placebo and 5 months fenfluramine treatment. After fenfluramine treatment blood serotonin levels fell, urinary catecholamine levels fell and the HVA/DA ratio rose. IQ and ACRT performance improved. On the ACRT subjects were asked to press a button to a rare target (500 Hz, P = 0.14) and to ignore higher pitched rare (2,000 Hz, P = 0.14) and frequent non-targets (1,000 Hz). After fenfluramine treatment N1 latencies increased. The scalp distribution of ERP maxima changes slightly with treatment. P3 maxima elicited by rare non-targets were recorded more rostrally after fenfluramine treatment. After rare non-targets N1 amplitudes at Fz decreased but P3 amplitudes at Pz increased. Early negativity after the rare non-target (particularly on the right side) was negatively correlated with the HVA/DA ratio. Subtraction of the P3 component elicited in a passive condition where no response was required from the active condition showed that P3 positivity to targets was halved with treatment. (In contrast Nd increased on fenfluramine treatment). Overall, N1 and P3 components showed greatest responsiveness to rare non-targets on fenfluramine. N1 but not P3 changes may represent slight improvement of attention-related function with treatment. Small changes in ERP latency and distribution, associated with the neuroleptic action of fenfluramine may be partly responsible for a mild improvement of IQ and ACRT performance on medication.

Adolescent↗

PubMed1990

Liquid chromatographic measurement of hydrophobicity constants for N-arylsulfonylglycine aldose reductase inhibitors.

The hydrophobicity constants for a series of aldose reductase inhibitors (ARIs) are determined by reversed-phase liquid chromatography. A series of reference compounds consisting of 23 barbituric acid derivatives are separated on two phenylsilica stationary phases over a range of methanol concentrations (30-80%) in 0.05 M phosphate buffer. Linear regression analysis of the measured log k' data is used to estimate the capacity factor in 100% water (log k'w) for each compound. The log k'w values are regressed against the shake-flask-measured 1-octanol-water partition coefficients, producing a correlation of 0.953. The same procedure is then used to estimate the log k'w values for a large group of ARIs and their log P values, calculated from the established relationship between log k'w and log P from the reference compounds. An initial analysis of the aldose reductase inhibitory activity of these compounds as a function of hydrophobicity alone fails to reveal a clear relationship, demonstrating the need for a multivariant approach for quantitative structure-activity analysis in this series of compounds.

Aldehyde Reductase↗

PubMed1990

Liquid chromatographic and mass spectral analysis of 1-(3,4-methylenedioxyphenyl)-1-propanamines: regioisomers of the 3,4-methylenedioxyamphetamines.

The title 1-(3,4-methylenedioxyphenyl)-1-propanamines represent positional isomers of the N-substituted 3,4-methylenedioxyamphetamines, clandestinely produced drugs frequently encountered by forensic laboratories. These propanamines are prepared by reductive amination of 3,4-methylenedioxypropiophenone with a series of N-alkylamines. Analytical methods are developed to distinguish these compounds from the MDA series. The ultraviolet spectra of the propanamines are very similar to those of the MDAs with absorption maxima at 284 and 236 nm. The propanamines are separated under reversed-phase liquid chromatographic conditions by using a C18 stationary phase and a mobile phase of acidic (pH 3) acetonitrile containing methanol and triethylamine. The relative retention properties of these compounds parallel those observed in the MDA series. The electron impact mass spectra of the propanamines are determined by GC-MS, and the fragmentation pattern clearly distinguishes these compounds from those of the MDA series having the same molecular weight.

3,4-Methylenedioxyamphetamine↗

PubMed1990

Liquid chromatographic studies on the aqueous solution conformation of substituted benzamides related to remoxipride.

A series of disubstituted benzamides related to the sterically hindered 2,6-dimethoxybenzamide drugs, such as remoxipride, are prepared. The structure-retention relationships for these compounds are studied on hydrocarbon stationary phases in various hydroorganic mobile phases. The 2,6-dimethoxybenzamide displays a very low capacity factor under these reversed-phase conditions, suggesting that steric crowding prevents the formation of an amide-methoxy N-H...O intramolecular hydrogen bond. The corresponding 2-hydroxy-6-methoxybenzamide shows a dramatic increase in affinity for the hydrocarbon stationary phase, which is characteristic of strong intramolecular hydrogen bonding in these compounds. These results suggest that the aromatic ring--carbonyl aqueous solution conformation is almost 90 degrees in amides like remoxipride and changes to coplanarity upon demethylation of one methoxy group.

Antipsychotic Agents↗

PubMed1990

Liquid chromatographic and spectral analysis of the 17-hydroxy anabolic steroids.

The liquid chromatographic properties of various 17-hydroxy anabolic steroids are examined under reversed-phase conditions. These anabolic steroids are now listed as controlled drugs in many states due to their abuse potential in athletics, body building, and other areas. These nonesterified steroids are separated on a C18 stationary phase with a 70% methanol in water mobile phase. In a few cases, two compounds display very similar retention properties. However, dual-wavelength detection at 254 and 280 nm allows for their differentiation. Reversed-phase retention parallels steroid lipophilicity based on hydroxyl and methyl group substituents. Also, those steroids containing a dienone substructure are more polar than steroids containing an enone moiety.

Anabolic Agents↗

PubMed1990

Liquid chromatographic and mass spectral analysis of the anabolic 17-hydroxy steroid esters.

The liquid chromatographic separation of the common anabolic steroid esters is accomplished in an isocratic reversed-phase system. These anabolic steroids are now controlled substances in many states in the U.S. due to their potential for abuse and misuse. The esters are designed to be very lipophilic materials for slow release from intramuscular injection sites. With a C18 stationary phase material and a mobile phase of methanol-water (85:15), the more lipophilic esters such as testosterone decanoate show a retention time of about 50 min. These esters of varying lipophilicity are well resolved by reversed-phase liquid chromatography, and this technique is very useful for the identification of these compounds in forensic samples.

Anabolic Agents↗

PubMed1990

Diastereoisomeric derivatization and liquid chromatographic analysis of N-(phenylsulfonyl)-2-phenylglycine aldose reductase inhibitors.

A series of (S)- and (R)-N-(phenylsulfonyl)-2-phenylglycines are synthesized as potential inhibitors of the enzyme aldose reductase. In vitro analysis of these compounds reveals that the S-enantiomers are more potent than the corresponding R-enantiomers and that the difference in potencies between enantiomeric pairs is dependent on the nature of the ring substituent. To ensure that the enantioselectivity observed does not reflect varying degrees of racemization during the synthesis of the N-(phenylsulfonyl)-2-phenylglycines, the enantiomeric purity of these products is determined by HPLC after chiral derivatization. Each 2-phenylglycine inhibitor is derivatized with R-alpha-methylbenzylamine, and the resulting diastereomers are analyzed using reversed and normal achiral stationary phases. Reversed-phase methods with C18 or phenyl stationary phases and solvent mixtures of acetonitrile or methanol in water do not provide satisfactory resolution of the diastereomers. However, normal-phase analyses with a silica stationary phase and mixtures of methanol, ethanol, or acetonitrile in chloroform provide good separations with relatively short analysis times. The normal-phase analyses demonstrate that a single diastereomeric amide forms from each N-(phenylsulfonyl)-2-phenylglycine product, establishing that these compounds do not racemize during synthesis.

Aldehyde Reductase↗

PubMed1990

Liquid chromatographic properties and aqueous solution stability of N-hydroxy-3,4-methylenedioxyamphetamine.

The reversed-phase liquid chromatographic properties of N-hydroxy-3,4-methylenedioxyamphetamine (NOHMDA) were determined on a C8 stationary phase specifically prepared for the separation of basic compounds. NOHMDA and several N-alkyl MDA derivatives displayed excellent peak shape on this stationary phase without the need for competing bases such as triethylamine. The k' values for NOHMDA varied with mobile phase pH in the range of 2.5 to 6.0, but the retention of the primary amine, MDA, and N-alkyl MDAs remained relatively constant over this range. The pKa value for NOHMDA was determined by titration to be 6.22 compared to a pKa of 10.04 for MDA. Thus, the variation of k' with mobile phase pH for NOHMDA may be a result of appreciable changes in degree of protonation. The stability of NOHMDA was found to decrease with an increase in aqueous solution pH. At pH 7.0 the degradation half-life was determined to be 49.8 h, which decreased to 2.57 h at pH 10.0. Above pH 10.0 the decomposition to the corresponding oxime was too fast for a reliable half-life determination.

3,4-Methylenedioxyamphetamine↗

PubMed1990

Pharmacokinetic studies of cimetidine hydrochloride in adult horses.

Histamine type II (H2) antagonists inhibit gastric acid secretion and are useful in treating gastric and duodenal ulcer disease. To provide some information on the pharmacokinetics of the H2 antagonist cimetidine, adult horses were given 3.3 mg/kg cimetidine intravenously (iv) or 3.3 and 10 mg/kg orally. Plasma cimetidine concentrations after 3.3 mg/kg orally were too low to measure. Following 3.3 mg/kg iv, cimetidine displayed two-compartment characteristics with a t1/2 of 0.083 +/- 0.039 h and t1/2 of 2.23 +/- 0.64 h. The total body clearance was 0.443 +/- 0.160 litre/h/kg and the mean residence time was 2.74 +/- 1.11 h. This clearance and t1/2 are similar to that in man. The volume of distribution (Vss) and volume of the central compartment (Vc) were 1.138 +/- 0.230 and 0.276 +/- 0.102 litre/kg, respectively. After a single oral dose of 10 mg/kg as crushed tablets, peak plasma concentration of 1.81 +/- 0.82 micrograms/ml occurred at approximately 1.4 h. Oral absorption of cimetidine appeared variable and slow with an extent of absorption of 0.296 +/- 0.183 and a mean residence time for absorption of 1.99 +/- 0.79 h. This was less than in man. Based on a desired average steady state plasma concentration of 1.0 microgram/ml, 11.0 mg/kg/day iv and 48 mg/kg/day orally can be recommended in adult horses.

Absorption↗