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Biomedical subjects

D E Richardson

Publications and source records attributed to D E Richardson.

At least 19 recordsLinked to original sources
PubMed1992

Cranioplasty using gentamicin-loaded acrylic cement: a test of neurotoxicity.

Cranioplasty represents a formidable challenge for neuro-surgeons, with a significant morbidity from both early and late wound infections. Polymethylmethacrylate (PMMA) is one of the most widely used materials in this setting. Despite the advantages of this material, such as ease of handling and inert biochemical properties, it is still a foreign body that is prone to infection. We present an animal model using a gentamicin-impregnated PMMA patch to assess the neurotoxicity as well as the efficacy of using this as an alternative material to lessen the infectious morbidity in this clinical setting. In part two of our experiment, we used a PMMA patch of similar weight and surface area in a physiological saline solution to determine the rate of gentamicin elution from the patch. The results obtained appear promising with no evidence of neurotoxicity and warrant further study to assess the clinical efficacy of PMMA in this setting.

Animals↗
PubMed1991

A sympathoinhibitory area in cat rostral medulla: its role in cardiovascular tone regulation and baroreflex.

We have found a medullary vasodepressor area in cat centered 3 mm rostral to the obex and just lateral to the compact division of the ambiguus nucleus. The area is compact, extending at most 1 mm in any direction. Microinjection of L-glutamate into this rostral depressor area (RDA) elicited acute hypotension and bradycardia. These responses were not reduced by either peripheral atropine blockade or bilateral vagotomy, but they were nearly abolished by peripheral phentolamine/propranolol blockade or high cervical cord transection. Bilateral reversible blockade of the RDA by local microinjection of the neuronal hyperpolarizing agent muscimol yielded chronic hypertension and tachycardia. Sympathetically mediated baroreflex, observed as a bradycardic response to a peripherally administered phenylephrine bolus in atropinized animals, was partially (50%) abolished during this same blockade. We conclude that the RDA contains sympathoinhibitory cells which are involved in the regulation of cardiovascular tone and in the expression of the sympathetic component of baroreflex.

Animals↗
PubMed1990

Central stimulation-induced analgesia in humans--modulation by endogenous opioid peptides.

Stimulation of the endogenous opiate system produced relief of somatosensory induced pain states. Stimulation of the nonopiate system can control pain from somatosensory causes as well as damage to the nervous system. Neither of these systems in themselves are rewarding or produce self-stimulation in humans, who have free choice of whether to use stimulation or not, except to reduce discomfort. Lack of pain in general produces lack of use of the stimulation system. Apparently, the descending opiate system for somatosensory pain control involves descending norepinephrine and serotonin pathways at an intermediate step through the dorsolateral funiculus of the cord. Enhancement of the opiate system can be produced by administration of L-Tryptophan and L-Dopa due to precursor loading of serotonin and norepinephrine. The endogenous opiate system, when activated by electrical stimulation, usually produces excellent control of somatosensory induced pain, but often is not effective for centrally produced pain. Stimulation of areas that produce analgesia that are nonopiate-dependent are usually more effective in reducing pain from damage to the nervous system itself than the opiate-dependent system, but this is sometimes the converse. While cross tolerance to morphine from electrical stimulation of the endogenous opiate system exists in animals, it does not seem to be a problem clinically as the abstinence syndrome and tolerance have not been a problem in humans.

Analgesia↗
PubMed1988

Platinum(II) binding to metallothioneins.

The reaction of equine renal metallothionein (MT) with excess K2PtCl4 at pH 2 results in a polymeric adduct containing 17 +/- 2 mol Pt/mol MT. A monomeric adduct containing 7 mol Pt/mol MT is obtained at neutral pH. Rates of reaction of Pt7MT with DTNB and iodoacetic acid are consistent with Pt2+ to cysteine thiolate coordination, and the extent of reaction in both cases is 11 +/- 2 mol cys/mol MT. Adducts from the reaction of K2PtCl4 with apoMT chemically modified at the N-terminal methionine residue, Cd7MT, and native MT are also reported. A structural model of Pt7MT is proposed in which the square planar tetrathiolate Pt(II) unit is incorporated into a three-metal beta cluster. Implications for the metabolism of platinum anticancer drugs are discussed.

Animals↗
PubMed1988

Pulmonary vascular responses to forebrain stimulation in the cat.

The effects of forebrain stimulation on the pulmonary vascular bed were investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. When pulmonary vascular tone was raised to a high steady level, direct electrical stimulation of the forebrain elicited a biphasic change in lobar arterial pressure. The response was characterized by an initial transient increase in lobar arterial pressure that was followed by a prolonged secondary decrease in pressure. When a delay coil was added to the extracorporeal perfusion circuit, the secondary vasodilator response was separated into initial brief and delayed prolonged components, suggesting that it was mediated in part by the release of a humoral factor. The entire response to forebrain stimulation was abolished by cervical cord section or freezing. The initial constrictor response and early brief dilator response were not blocked by classic pharmacological blocking agents. The delayed humorally mediated vasodilator response was blocked by propranolol or ICI 118551, indicating that it was mediated by a circulating factor with beta 2-stimulating properties. The delayed vasodilator response was associated with a large increase in arterial epinephrine levels, and this rise in plasma epinephrine was not altered by propranolol. The present data suggest that electrical stimulation of the forebrain causes a prolonged pulmonary vasodilator response that is mediated by way of a descending pathway, which results in a large rise in arterial epinephrine levels.

Animals↗
PubMed1988

Zinc suppression of free radicals induced in cultures of rat hepatocytes by iron, t-butyl hydroperoxide, and 3-methylindole.

The effect of zinc on lipid peroxidation initiated by either ferric-nitrilotriacetate, t-butyl hydroperoxide, or 3-methylindole was studied using primary monolayer cultures of rat liver parenchymal cells. The malondialdehyde content of the cells and culture medium was used to estimate the extent of lipid peroxidation. As the zinc concentration of the culture medium was increased from 1 to 48 microM, peroxidation was diminished. Cellular zinc and metallothionein levels were proportionally increased by supplemental zinc. Zinc supplementation of the medium inhibited NADPH-cytochrome c reductase activity and stimulated glutathione peroxidase activity. The uptake of iron into the hepatocytes was significantly reduced as the level of zinc was raised, suggesting that zinc antagonizes uptake of chelated iron into isolated hepatocytes and in this way blocks iron-induced peroxidation. Furthermore, induction of metallothionein synthesis by zinc may contribute to the reduction in free radicals. Spectra from electron spin resonance studies, using phenylbutylnitrone as a spin-trapping reagent, demonstrated that free radical production was inversely related to the zinc concentration of the culture medium. Spin trap data suggest that metallothionein added to lysed cells in vitro decreases free radical production. Studies using the spin trap, 3,3,5,5-tetramethylpyrroline-N-oxide indicated that cumulatively the predominant radical present in the cultures was a phenyl radical with hydroperoxide or methylindole. Collectively, our data demonstrate that zinc inhibits free radical production and lipid peroxidation in cultured hepatocytes. The mode of action of zinc could occur via free radical scavenging by zinc-induced metallothionein and/or by processes related to cytochrome P-450 and glutathione peroxidase, since these were also found to be sensitive to zinc supplementation levels of the culture medium.

Animals↗
PubMed1987

Allosteric interactions in sipunculid and brachiopod hemerythrins.

Chemical and spectroscopic consequences of allosteric interactions for ligand binding to sipunculid (Phascolopsis gouldii) and brachiopod (Lingula reevii) hemerythrins (Hrs) have been investigated. Possible allosteric effectors for homotropic effects in sipunculid Hrs have been examined, but only reduction in ligand affinity is observed without cooperativity. In contrast to sipunculid Hr, L. reevii Hr binds O2 cooperatively in the pH range 7-8 and exhibits a Bohr effect. Spectroscopic comparisons of the sipunculid and brachiopod Hrs show no significant differences in the active site structures; therefore, modulation of oxygen affinity is attributable to effects linking the site to quaternary structural changes in the octamer. Oxygen equilibria can be fit with a conformational model incorporating a minimum of three states, tensed (T), relaxed (R), and an R-T hybrid. Resonance Raman spectra of L. reevii oxyHr show a shift in the peroxo stretching frequency when the pH is lowered from pH 7.7 (predominantly R oxyHr) to pH 6.3 (a mixture of R, T, and R-T hybrid), but P. gouldii Hr does not have a frequency shift under the same conditions. In contrast to hemoglobins, ligand binding to the deoxy and met forms is noncooperative for brachiopod (and sipunculid) Hrs. It is thus suggested that conformational changes in the protein are linked to the oxidation state change that accompanies oxygenation of the coupled binuclear iron site (deoxy [FeIIFeII]----oxy [FeIIIFeIII]). The total allosteric energy expended in oxygenation is about 1.4 kcal/mol, and such a shift is possible in the relaxed-tense conversion with relatively limited constraints of the iron coordination environment via the protein quaternary structure. The mechanism of cooperativity in the binuclear copper oxygen carrier hemocyanin is discussed in light of these results.

Allosteric Regulation↗
PubMed1987

Paleocerebellar stimulation induces in vivo release of endogenously synthesized [3H]dopamine and [3H]norepinephrine from rat caudal dorsomedial nucleus accumbens.

The influence of cerebellar vermis stimulation on noradrenergic and dopaminergic activity in the nucleus accumbens was investigated in anesthetised rat. Artificial cerebral spinal fluid containing [3H]tyrosine was continuously circulated through a unilateral push-pull cannula implanted in the nucleus accumbens. Fifteen-minute perfusate samples were collected serially for three consecutive 1-h periods designated pre-, during-, and post-stimulation. The stimulation was applied through a bilateral electrode located subdurally over the fifth vermal lobe. The [3H]norepinephrine and [3H]dopamine components in each sample were isolated by alumina extraction and high-pressure liquid chromatographic fractionation, and then quantified by liquid scintillation counting. For cannula locations in the caudal dorsomedial nucleus accumbens, levels of both [3H]catecholamines were found to be significantly higher during stimulation compared to the prestimulation baselines, and [3H]norepinephrine remained significantly elevated through the post-stimulation period. The relative increase during stimulation for [3H]norepinephrine (130%) was nearly twice that for [3H]dopamine (70%). These results indicate that vermal activation can significantly raise both noradrenergic and dopaminergic in vivo activity in the caudal dorsomedial nucleus accumbens, and provide a possible mechanism for explaining previously demonstrated influences of paleocerebellum upon affective components of behavior.

Animals↗
PubMed1987

Does epileptic pain really exist?

Painful seizures do exist, but are usually caused by uncontrolled muscle contractions that produce pain. Heretofore, no cases of seizures of the pain system have been reported. We will present a case of chest wall pain with episodic, severe exacerbation of the localized pain associated with focal muscle contractions. The episodes of severe pain could be provoked by stimulation of the internal capsule, producing repeated episodes of pain/muscle activity. The symptoms could be stopped by intravenous diazepam and reduced by periventricular grey stimulation.

Chest Pain↗
PubMed1986

Isolation and characterization of a high molecular weight stable pink form of uteroferrin from uterine secretions and allantoic fluid of pigs.

A pink, high molecular weight form of uteroferrin (Uf) has been isolated from uterine secretions and allantoic fluid of pigs. This protein fraction (denoted FIII) which is relatively stable under physiological conditions of pH, ionic strength, and temperature has a molecular weight of about 80,000, a value approximately twice that of purple Uf (Mr approximately 35,000) isolated from a separate fraction (FIV) by gel filtration. The visible absorption spectrum, EPR signal, and acid phosphatase activity of Uf in FIII are almost identical to those of FIV Uf after the latter has been reduced by 2-mercaptoethanol. However, unlike reduced FIV Uf, the pink, high molecular form does not revert to purple, nor does it show loss of EPR signal and phosphatase activity in the presence of oxygen. In addition, it does not become purple at orthophosphate concentrations which inhibit Uf acid phosphatase activity. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate has shown that FIII consists of approximately equal amounts of Uf polypeptides (Mr = 35,000 and 37,000) and a group of three polypeptides (Mr = 40,000, 46,000, and 50,000) antigenically unrelated to Uf. The latter share a common epitope not found on Uf and are probably differentially processed forms of the same protein. FIII can be dissociated by pH conditions below 5.0, by exposure to antibodies raised against Uf or the associated polypeptides, and by sodium dodecyl sulfate at 100 degrees C. The polypeptides in FIII are not therefore linked by disulfide bonds. Treatment with dimethyl suberimidate, however, results in a cross-linked complex (Mr approximately 82,000) consisting of Uf and the associated polypeptides. It is concluded that this high Mr form of Uf is a heterodimer of fully activated Uf and a second polypeptide of unknown function.

Acid Phosphatase↗
PubMed1986

Autopsy analysis of the safety, efficacy and cartography of electrical stimulation of the central gray in humans.

Electrical brain stimulation is effective in controlling certain intractable chronic pain syndromes in humans, but the specific target site(s) for stimulation producing a maximal analgesic effect is (are) not well defined. This prospective study correlates the clinical results of chronic stimulation of the periaqueductal gray (PAG) and periventricular gray (PVG) matter in humans with the anatomic site of electrode placement as determined at autopsy, and documents the histologic reactions to electrode implantation and electrical stimulation of the area. Seven patients underwent electrode implantation to control their chronic pain; two had electrodes implanted bilaterally. All patients obtained complete analgesia with stimulation, although 3 subsequently found the stimulation to have diminished efficacy. The opiate antagonist naloxone reversed the analgesia in the 4 patients so tested. All 7 patients later died of causes unrelated to electrode implantation or stimulation. Postmortem analysis showed that, for 6 of the 9 electrodes implanted, the electrode tip was located in the ventrolateral PAG at the level of the posterior commissure; the other 3 electrodes were found in the white matter adjacent to the PAG. No evidence of gliosis or parenchymal reaction was observed along the tracts and tips of the electrodes. The results indicate that the ventrolateral PAG and PVG matter at the level of the posterior commissure is the optimal site for therapeutic electrical brain stimulation for opiate-responsive pain in humans.

Adult↗
PubMed1978

Enkephalin-like material elevated in ventricular cerebrospinal fluid of pain patients after analgetic focal stimulation.

Enkephalin-like activity has been measured in the ventricular cerebrospinal fluid of patients with intractable pain. Electrical stimulation of periventricular brain sites resulted in significant decrease in persistent pain in these subjects. This analgesia, which was blocked by naloxone in 80% of the cases, was accompanied by a significant rise in ventricular enkephalin-like activity, as measured by two different methods. The results present evidence of in vivo release of enkephalin-like material in humans and suggest that stimulation analgesia may be partially due to this release.

Brain↗
PubMed1978

Appearance of beta-endorphin-like immunoreactivity in human ventricular cerebrospinal fluid upon analgesic electrical stimulation.

beta-Endorphin-like immunoreactivity in human ventricular cerebrospinal fluid was measured with a specific radioimmunoassay. The subjects were undergoing a surgical procedure for relief of chronic intractable pain. This procedure involved the focal stimulation of a medial thalamic site adjacent to the wall of the third ventricle. Samples were collected before and during the analgesic stimulation. No beta-endorphin-like immunoreactivity could be detected prior to stimulation, suggesting that baseline levels are below 25 fmol/ml of cerebrospinal fluid. Electrical stimulation led to substantial increases (13- to 20-fold) in immunoreactive material in every subject. These results suggest that beta-endorphin-like material can be released into the ventricular system and may contribute to the pain blockade that results from periventricular stimulation.

Analgesia↗
PubMed1977

Pain reduction by electrical brain stimulation in man. Part 1: Acute administration in periaqueductal and periventricular sites.

Acute studies performed in five patients indicate that electrical stimulation of the brain could be a powerful tool for the reduction or control of intractable pain. While chronic or spontaneous pain could be relieved by stimulation of the periaqueductal gray matter, the accompanying side effects render it impossible to stimulate this site regularly. On the other hand, stimulation of medial thalamic sites, particularly medial to the nucleus parafascicularis, yielded good relief of chronic pain at parameters which did not cause many undesirable side effects. The same parameters also produced inhibition of acute pain in two of the five patients.

Aged↗
PubMed1977

Pain reduction by electrical brain stimulation in man. Part 2: Chronic self-administration in the periventricular gray matter.

Electrical stimulation of the periventricular gray matter is an effective means of relieving several types of pain without destruction of neural tissue. The effects are long lasting, often bilateral, and with judicious use do not appear subject to adaptation. However, sustained uninterrupted stimulation for several hours does lead to a reversible decrease in effectiveness. Side effects from stimulation are minimal and cause little or no untoward emotional changes. The results are discussed in terms of activation of an endogenous pain inhibitory mechanism that involves naturally occurring opiate-like factors such as the enkephalins and endorphins.

Adult↗