Search PubMed⌕ Search

Biomedical subjects

C R Clark

Publications and source records attributed to C R Clark.

At least 109 records · Page 6Linked to original sources
PubMed1989

Application of a new radiometric high-performance liquid chromatographic assay to define physostigmine pharmacokinetics in guinea pigs.

A sensitive high-performance liquid chromatographic method was developed to determine pharmacokinetic parameters of [3H]physostigmine from serial plasma samples from guinea pigs. Physostigmine was totally resolved from its metabolite, eseroline. The limit of sensitivity was 0.05 ng/ml from 0.2 ml plasma. Extraction efficiency was 99.6%. Within-run and among-run coefficients of variation (n = 6) for 0.2, 0.75, 1.5 and 2.5 ng/ml [3H]physostigmine ranged from 0.7 to 20% and 16 to 32%, respectively. Physostigmine (5 micrograms/kg) intramuscularly administered to the guinea pig (n = 6) reached maximum serum concentration (1.5 ng/ml) in 26 min. The apparent volume of distribution and systemic clearance were 1.4 l/kg and 26 ml/min/kg, respectively. This method was successful in defining physostigmine pharmacokinetic parameters in guinea pigs and can be employed for other small animal pharmacokinetic studies.

Animals↗
PubMed1989

Evaluation of effectiveness of a facet wiring technique: an in vitro biomechanical investigation.

The effects of facet wiring procedure commonly used for stabilizing cervical spines after laminectomy or bilateral facet dislocation on the motion behavior of whole cervical spines are investigated using a Selspot II system. A fresh human ligamentous intact specimen was potted at T1/T2 vertebra and clinically relevant loads applied to the topmost vertebra (C2) of the specimen. The resulting three rotational components of each of the five vertebral bodies (C3-C7) were recorded. Specimen was injured to mimic total laminectomies at C5 and C6 vertebral levels and tested again. The injured specimen was stabilized, using a facet wiring construct, across C4-C7 segment before testing for the final time. The injured specimens, compared to the intact specimens, demonstrated an increase in flexion-extension of about 10%. Facet wiring imparted stability to the cervical spine by stiffening segments up to roughly four times intact values.

Aged↗
PubMed1989

Catecholamines and the covert orientation of attention in humans.

The role of brain catecholamines in covert orienting was tested in normal subjects using a cued reaction time paradigm which measures the directional engagement, disengagement and movement of attention. Droperidol and clonidine were administered intravenously to suppress central dopamine and noradrenaline transmission. Both drugs produced reductions in the cost of invalid cueing without change in the benefit of valid cueing suggesting that both noradrenaline and dopamine are involved in facilitating the disengagement of attention. These results are relevant to the slowed disengagement observed with parietal lesions in monkeys and humans since this region of the cortex associated with visuospatial analysis receives a dense innervation by both dopamine and noradrenaline projections in primates.

Adolescent↗
PubMed1989

Corpus callosum surgery and recent memory. A review.

A number of clinical reports have cited memory disturbances in surgical cases involving section of the corpus callosum. This review, however, shows that persistent impairment of recent memory has tended to occur only in cases where there has been concurrent extracallosal damage, particularly to the fornix and its connections. Both the timing and sensitivity of psychometric tests as well as the availability of preoperative baselines are all important factors in determining the reliability of memory assessment following callosal surgery. A minimal delay of one year between surgery and final memory testing is needed because intellectual functions have been shown to improve markedly during the 12 months following callosal section. The use of discriminating psychometric tests with comparisons before and after operation is desirable, since global memory tests are relatively insensitive to disorders of recent memory.

Animals↗
PubMed1989

Liquid chromatographic studies on the aqueous solution conformation of substituted benzamide drug models.

The aqueous solution conformation of a series of model benzamides related to the orthopramide dopamine receptor antagonists is evaluated by reversed-phase liquid chromatography (LC). The structure-retention relationship studies demonstrate the existence of an intramolecular hydrogen bond formed in aqueous solution for these compounds. The six-membered pseudoring formed by the association of the amide N-H and the oxygen of the 2-methoxy group (N-H...O) produces enhanced reversed-phase retention (increased capacity factors, k') relative to the 3- and 4-isomers. Deletion of either the acceptor oxygen or the donor N-H results in decreased C18 retention of the 2-isomer relative to the 3- and 4-isomers. These structure-retention relationship studies reveal the value of reversed-phase LC methods for evaluation of the aqueous solution conformation of the orthopramide-type compounds. Further studies show that N-substituted 2-hydroxybenzamides are intramolecularly associated in aqueous solution through either N-H...O or O-H...O six-membered rings. The 6-methoxysalicylamides are believed to be stabilized through O-H to carbonyl oxygen bonding in addition to the N-H...O pseudoring. For the 2,6-dimethoxybenzamides, steric factors prevent methoxy-amide coplanarity, thus no intramolecular hydrogen bond is formed. The result is a dramatic decrease in retention for the 2,6-isomer relative to the other positional isomers. These studies suggest that remoxipride and related 2,6-dimethoxybenzamides cannot form the six-membered pseudoring believed to be topographically equivalent to the aromatic ring in dopamine.

Benzamides↗
PubMed1989

Liquid chromatographic and mass spectral analysis of 1-(3,4-methylenedioxyphenyl)-3-butanamines, homologues of 3,4-methylenedioxyamphetamines.

The 1-(3,4-methylenedioxyphenyl)-3-butanamines (HMDAs) are prepared via reductive amination of the corresponding ketone with a series of low molecular weight alkylamines. These amines are homologues of the N-substituted 3,4-methylenedioxyamphetamines (MDAs). Compounds of the HMDA series have UV absorption properties similar to the MDAs because both series contain the same 3,4-methylenedioxyphenyl chromophore. The HMDAs are separated via reversed-phase liquid chromatographic methods using a C18 stationary phase and an acidic aqueous acetonitrile mobile phase. The mass spectra of these potential designer drugs are very similar to the spectra of the MDA homologues having the same N-substituent.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Esophageal perforation following anterior cervical spine surgery.

The authors surveyed the Cervical Spine Research Society to compile a series of esophageal perforations following anterior cervical spine surgery. Twenty-two cases were assembled. Six occurred at the time of surgery, 6 in the postoperative period, and 10 weeks to months later. Eight surgeries were because of fracture. Hardware was implicated in 25% of cases occurring after surgery. Diagnosis was confirmed most often by direct vision at reexploration or esophography. Treatment usually consisted of drainage, repair, and parenteral antibiotics; 2 cases were successfully treated by enteral feeding and antibiotics alone. There was one fatality, and all patients required prolonged hospitalization. Cervical fracture and the use of hardware may be associated with this complication. Clinical suspicion and esophography are important diagnostic tools. Drainage and parenteral antibiotics are recommended treatment.

Adult↗
PubMed1989

Kinematics of the cervical spine following discectomy and stabilization.

The immediate biomechanical stability of the cervical spine following discectomy and stabilization is described. Fresh human ligamentous spines (C2-T2) were potted, and clinically relevant loads were applied by a loading frame attached to the C2 vertebra of each specimen. A set of three infrared light-emitting diodes (LEDs) were attached rigidly to each of four vertebrae (C4 to C7) to record their spatial locations after each load step application using a Selspot II (Selcom Selective Electronic, Inc., Valdese, North Carolina) system. The specimen was tested in the intact state, following discectomy at the C5-6 intervertebral level, following insertion of a bone graft in the intervertebral space, and following the application of an anterior metal plate. The load-deformation data of the injured and stabilized tests were normalized with regard to the corresponding results of the intact specimens. At the injured level (C5-6), the load-deformation results indicated a highly significant increase in motion in flexion (66.6%), extension (69.5%), lateral bending (41.3%), and axial rotation (37.9%). After the insertion of the bone graft, a significant decrease in motion was seen in the effected segment in extension (-45.9%), with similar reductions in lateral bending and axial rotation and a smaller reduction in flexion. The application of an anterior metal plate in addition to the bone graft at the injured level provided significant reduction in motion (-70%) in all load modalities. This data may have clinical relevance regarding the role of internal fixation in cases of severe spine instability.

Biomechanical Phenomena↗
PubMed1989

Mechanisms of abnormal endothelium-dependent vascular relaxation in atherosclerosis: implications for altered autocrine and paracrine functions of EDRF.

The present studies were performed to determine if abnormal endothelium-dependent vascular relaxation in atherosclerosis is due to decreased production or release of endothelium-derived relaxing factor (EDRF) by atherosclerotic rabbit vessels or if atherosclerotic vessels are less sensitive to the relaxing effects of EDRF. EDRF release was quantified using two approaches, by the response of bioassay detector vessels and also by the activation of guanylate cyclase within cultured endothelial cells. Using these assays, atherosclerotic vessels were found to release significantly less EDRF than normal vessels in response to both receptor- and nonreceptor-mediated stimuli. Relaxations of normal and atherosclerotic vessels to luminally applied EDRF (derived from normal rabbit aortas stimulated by the calcium ionophore, A23187) and nitric oxide, a putative EDRF, were also studied. Atherosclerotic vessels were more sensitive to EDRF than normal vessels, and equally sensitive to nitric oxide. Additional studies performed in organ chambers failed to demonstrate augmented constriction of atherosclerotic vessels in response to acetylcholine in the presence or absence of methylene blue or LY83583, compounds which inhibit the effect of EDRF. We conclude that decreased EDRF release is the principal underlying mechanism responsible for abnormal endothelium-dependent vascular relaxation in atherosclerosis.

Acetylcholine↗
PubMed1989

Comparative acute toxicity of shale and petroleum derived distillates.

In anticipation of the commercialization of its shale oil retorting and upgrading process, Unocal Corp. conducted a testing program aimed at better defining potential health impacts of a shale industry. Acute toxicity studies using rats and rabbits compared the effects of naphtha, Jet-A, JP-4, diesel and "residual" distillate fractions of both petroleum derived crude oils and hydrotreated shale oil. No differences in the acute oral (greater than 5 g/kg LD50) and dermal (greater than 2 g/kg LD50) toxicities were noted between the shale and petroleum derived distillates and none of the samples were more than mildly irritating to the eyes. Shale and petroleum products caused similar degrees of mild to moderate skin irritation. None of the materials produced sensitization reactions. The LC50 after acute inhalation exposure to Jet-A, shale naphtha, (greater than 5 mg/L) and JP-4 distillate fractions of petroleum and shale oils was greater than 5 mg/L. The LC50 of petroleum naphtha (greater than 4.8 mg/L) and raw shale oil (greater than 3.95 mg/L) also indicated low toxicity. Results demonstrate that shale oil products are of low acute toxicity, mild to moderately irritating and similar to their petroleum counterparts. The results further demonstrate that hydrotreatment reduces the irritancy of raw shale oil.

Alkanes↗
PubMed1989

Arthrodesis of the cervical spine in rheumatoid arthritis.

Forty-one patients who had rheumatoid arthritis were treated with a cervical arthrodesis and were followed for a minimum of twenty-three months. Twenty patients had had an isolated atlanto-axial subluxation; five, isolated cranial settling; and four, subaxial subluxation alone. Twenty patients had an atlanto-axial arthrodesis; sixteen, an occipitocervical arthrodesis; and five, a posterior arthrodesis of the subaxial spine. In addition, two patients had a transoral odontoidectomy and one, an anterior cervical vertebrectomy. At the latest follow-up, thirty-six (88 per cent) of the patients had osseous union, two had fibrous union but were stable, and three had a non-union. All of the problems with union occurred in the patients who had had an isolated atlanto-axial arthrodesis. Clinically, twenty-seven (66 per cent) of the patients had improved, fourteen were unchanged, and none were worse. The preoperative neurological status remained the same postoperatively in thirty patients (73 per cent) and it improved in eleven (27 per cent). Twenty-one of the twenty-three patients who had had marked pain preoperatively had little or no pain at the latest follow-up. Complications included a transient hemiparesis in one patient, a superficial wound infection in two, displacement of an anterior graft in one, a broken wire in three, and erosion of methylmethacrylate into the outer part of the occipital cortex in one. Four patients died, but not as a result of the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Cholecystokinin modulation of [3H]noradrenaline release from superfused hypothalamic slices.

Interactions between cholecystokinin (CCK) and noradrenaline (NA) have been studied by investigating the effect of sulphated cholecystokinin octapeptide (CCK-8) on potassium (K+)-stimulated release of [3H]NA from superfused hypothalamic slices. NA and the alpha 2-agonist clonidine markedly inhibited [3H]NA release, while the alpha-antagonist yohimbine facilitated the release process. CCK was found to give a significant, albeit small, inhibition of [3H[NA release, which was maximal at a concentration of 10(-8) M. These results provide evidence that CCK-8 can exert an inhibitory effect on hypothalamic NA transmission and offer one possible mechanism for the interaction of CCK and NA in the hypothalamic control of food intake.

Animals↗
PubMed1988

Kinematics of the cervical spine: effects of multiple total laminectomy and facet wiring.

The effect of multiple-level total laminectomies followed by stabilization on the load-deformation behavior of the cervical spine is described. Fresh human ligamentous cervical spines (C2-T2) were potted and clinically relevant load types applied via a loading frame attached to the C-2 vertebra of the specimen. A set of three infrared light-emitting diodes (LEDs) were attached rigidly to each of five vertebrae (C3-7) to record their spatial locations after each load step application, using a Selspot II system. The specimen was tested again after total laminectomy performed on C5. The supraspinous, interspinous, and flavum ligaments between the C4-5 and C5-6 motion segments were cut; thereafter, the vertebral arch was removed. The specimen testing was resumed after inducing injury at C-6 in a similar fashion. The specimen was stabilized, using a facet wiring construct, across the C4-7 segment before testing for the final time. The load-deformation data of the injured and stabilized tests were normalized with regard to the corresponding results of the intact test. In flexion-extension mode, an increase in motion of about 10% after laminectomies was observed. Facet wiring was found to be an effective technique to stabilize injured cervical spines (approximately equal to 80% reduction in motion, compared with intact spines, was observed.

Biomechanical Phenomena↗
PubMed1988

Moment-rotation relationships of the ligamentous occipito-atlanto-axial complex.

The relationships between applied pure moments at the occiput (C0) and the resulting rotations at the atlanto-occipital (C0-C1) and atlanto-axial (C1-C2) joints are quantified. In axial twist, with a moment of 0.3 Nm, a mean rotation of about 2.5 degrees and 23.3 degrees was observed at C0-C1 and C1-C2 units respectively. Both the atlas and axis contributed to produce lateral bending motion. The ratio between extension and flexion rotations at C0-C1 was 2.5:1. Lateral bending and axial rotations were strongly coupled to each other. The occipito-atlanto-axial complex exhibited a large 'neutral zone' compared to lower cervical spine segments. The likely clinical significance of these findings are discussed.

Aged↗
PubMed1988

Behavioral effects of alpha-benzyl-N-methylphenethylamine (ABNMP), a methamphetamine analog: inhibition by ketanserin and para-chlorophenylalanine (PCPA).

Acute administration of alpha-benzyl-N-methylphenethylamine (ABNMP) induces lateral heavings, straub tail, backward locomotion, and hindlimb abduction-which are all components of the serotonin (5-HT) syndrome. Ketanserin, a 5-HT-2 receptor antagonist and pretreatment with the 5-HT neurotoxin parachlorophenylalanine (PCPA) attenuated the manifestation of these behavioral abnormalities. These results suggest that ABNMP may cause an acute release of 5-HT similar to that elicited by para-chloroamphetamine.

Animals↗