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Biomedical subjects

G D Clark

Publications and source records attributed to G D Clark.

At least 37 records · Page 2Linked to original sources
PubMed1994

Ethical dilemmas and decisions concerning the do-not-resuscitate patient undergoing anesthesia.

The growing geriatric population in this country makes it increasingly difficult to deal with the number of do-not-resuscitate (DNR) orders. In part, this is due to an increase in the number of elderly undergoing anesthesia and surgery. It can also be attributed to a rise in complex legal, ethical, and moral issues these orders pose for the healthcare professional caring for the DNR patients, including anesthetists. The term "DNR" is confusing to many, including healthcare professionals. As patients progress through the perioperative period, this confusion is compounded by the fact that administration of anesthesia encompasses interventions that include intubation, ventilation, and fluid replacement. These interventions may be regarded as resuscitative efforts outside the operating room. The anesthetist must identify and sort through a maze of conflicting courses of action, which must match the patient's desires and personal rights. The topic of DNR orders is addressed as well as some of the moral and ethical dilemmas they pose for the Certified Registered Nurse Anesthetist (CRNA). Some solutions are offered to help the nurse anesthetist make those decisions that are most "right" for the patient.

Decision Making↗
PubMed1993

Recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis lesions of the respiratory tract affect both children and adults. The etiology currently accepted by researchers is the human papillomavirus. Though relatively rare in children, these lesions can be serious and potentially fatal if the airway should become compromised or obstructed. Of the numerous treatments tested since recurrent respiratory papillomatosis was first described, the surgical laser is the most effective tool for controlling these lesions. A 5-year-old female patient who suffered from recurrent respiratory papillomatosis since the age of 2 and had over 80 laser treatments in a 3-year period is discussed. Laser and interferon administered concurrently lessened the frequency of laser therapy in this patient. Variations in number and size of recurrent respiratory papillomatosis lesions present a challenge to the anesthetist. Delivery of anesthesia requires precise preanesthetic planning and coordination. Since these lesions are most prevalent in the laryngeal airway, the surgical field must be shared by the anesthetist and the surgeon. The etiology, medical and physical therapeutic management, anesthetic management, and complications of patients with RRP are presented.

Child, Preschool↗
PubMed1992

Enhancement of hippocampal excitatory synaptic transmission by platelet-activating factor.

The biologically active lipid platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine; PAF) is a mediator of inflammatory and immune responses, and it accumulates in the brain during convulsions or ischemia. We have examined whether PAF may play a second messenger role in the central nervous system by studying effects on synaptic transmission in cultured hippocampal neurons. Carbamyl-PAF, a nonhydrolyzable PAF analog with a similar pharmacologic profile, augmented glutamate-mediated, evoked excitatory synaptic transmission and increased the frequency of spontaneous miniature excitatory synaptic events without increasing their amplitude or altering their time course. This compound had no significant effect on gamma-aminobutyric acid-mediated inhibitory synaptic responses. Lyso-PAF, the biologically inactive metabolic intermediate, had no effect on synaptic transmission. Moreover, the enhancement of excitatory synaptic transmission by carbamyl-PAF was blocked by a PAF receptor antagonist. These results indicate a specific presynaptic effect of PAF in enhancing excitatory synaptic transmission in cultured rat hippocampal neurons.

Animals↗
PubMed1992

Wheat germ agglutinin enhances EPSCs in cultured postnatal rat hippocampal neurons by blocking ionotropic quisqualate receptor desensitization.

1. The effect of the lectin wheat germ agglutinin (WGA), an inhibitor of ionotropic quisqualate receptor desensitization, on both evoked and spontaneous fast excitatory postsynaptic events was examined in cultured postnatal rat hippocampal neurons with the use of whole cell recordings. 2. WGA, at 580 nM, potentiated evoked fast excitatory postsynaptic currents (EPSCs) by increasing the amplitudes by 100 +/- 27% (mean +/- SE) and the time constant of decay from 5.8 +/- 0.6 to 7.9 +/- 0.5 ms. The increases in these parameters were not accompanied by changes in the current-voltage (I-V) relationship or pharmacological profile of the fast EPSCs. 3. WGA did not alter the amplitude or time course of decay of inhibitory postsynaptic currents (IPSCs), and it did not alter neuronal input resistance or action potentials. 4. WGA increased the amplitude of spontaneous fast miniature EPSCs (MEPSCs), defined as spontaneous EPSCs recorded in the presence of tetrodotoxin, by 53 +/- 11% and increased the time required to decay to 50% of the peak amplitude by 48 +/- 23%. These changes were not associated with a change in the rate of MEPSC occurrence. 5. These results suggest that WGA augments hippocampal excitatory postsynaptic events via a postsynaptic mechanism. The results further imply that ionotropic quisqualate receptor desensitization can modulate the amplitude and time course of decay of fast excitatory synaptic events. Thus desensitization may be one factor that regulates fast excitatory synaptic transmission.

Animals↗
PubMed1992

Measurement of free desipramine in serum by ultrafiltration with immunoassay.

We developed an ultrafiltration method for assaying free desipramine (DMI) in serum. An ultrafiltrate of DMI-containing serum was prepared by centrifugation through an Amicon Centrifree micropartition filter. Syva DMI solid-phase extraction (SPE) columns were used to extract the DMI from the serum and ultrafiltrate. The Syva monoclonal EMIT assay was used to quantify the DMI in the extract. In some experiments, the percent free DMI was quantified with radioactivity. Nonspecific losses of DMI in serum to the ultrafilter system were low (recoveries > 91%). Extraction of [3H]DMI from phosphate-buffered saline (to mimic serum ultrafiltrate) with the Syva SPE system was quantitative (recoveries of 98.4% +/- 4.6%). Free DMI concentrations, derived from serum containing 2.5-2500 micrograms/L DMI, were determined by ultrafiltration; results agreed well with values determined by equilibrium dialysis, the average percent of free DMI being 18.4% +/- 0.25% and 15.9% +/- 0.51%, respectively. To increase the sensitivity of the free DMI assay in the therapeutic range (total DMI 125-300 micrograms/L), we increased fourfold the ultrafiltrate volume applied to the SPE column. For free DMI at 11-130 micrograms/L, the within-run and between-run CVs for the ultrafiltration method were < 9% and < 15%, respectively. Binding of DMI to serum proteins decreased over the pH range 6.0-8.0, although temperatures between 20 and 28 degrees C did not affect binding. The ultrafiltration assay is fast, accurate, simple, and adaptable to standard laboratory instrumentation.

Desipramine↗
PubMed1992

Adaptation of the de Vilbiss atomizer for the delivery of topical anesthesia.

A de Vilbiss atomizer was adapted for delivery of topical anesthesia to the nasal, oral, pharyngeal, laryngeal, and tracheal tissues prior to outpatient bronchoscopy under monitored anesthesia care for a patient who must remain in the sitting position. The adaptation, utilizing a Baxter Airlife oxygen tubing attached on one end to an oxygen source and the other to the port of a de Vilbiss atomizer, contained a small perforation on the oxygen tubing that allowed for thumb-controlled oxygen flow and delivery of local anesthesia. Anesthetization of the oropharyngeal membranes and suppression of the gag reflex was accomplished primarily by gargling with dyclonine (1%) and dyclonine (.5%) administered through this adapted atomizer. An oral airway lubricated with 2% lidocaine jelly was inserted to direct the delivery of the local anesthetic spray since a laryngoscope was unable to be inserted safely in the sitting position. Local anesthesia of lidocaine (4%) was administered transtracheally and dyclonine (.5%) was delivered through the atomizer along the oral airway with each inspiration to anesthetize the larynx and trachea for a total of 220 mg lidocaine and 300 mg dyclonine, respectively. This method of local anesthetic application for outpatient bronchoscopy proved to be successful in the patient with a compromised cardiac and pulmonary status who is unable to lie flat.

Administration, Topical↗
PubMed1990

The effect of agonist concentration, membrane voltage and calcium on N-methyl-D-aspartate receptor desensitization.

The effects of agonist concentration, transmembrane voltage and calcium on the glycine-independent desensitization of N-methyl-D-aspartate receptors were examined in voltage-clamped postnatal rat hippocampal neurons. In the presence of 1 micron glycine and 1 mM calcium, both the time-course and degree of N-methyl-D-aspartate desensitization were dependent on agonist concentration. Transmembrane voltage influenced both the rate and degree of desensitization with a more rapid rate and greater degree at negative holding potentials. Both the time-course and the degree of desensitization were influenced by extracellular calcium in a dose-dependent manner. N-Methyl-D-aspartate desensitization is not augmented by activation of voltage-gated calcium currents and is more pronounced in the presence of intracellular calcium chelators, suggesting that the site of action of calcium in promoting desensitization is extracellular. Although a physiological role for N-methyl-D-aspartate desensitization has not been demonstrated, the process is observed over a range of agonist concentrations, is prominent near resting membrane potential and is regulated by physiologic concentrations of calcium. Thus desensitization could be an important neuroprotective mechanism during periods of prolonged glutamate exposure.

Animals↗
PubMed1990

Blockade of desensitization augments quisqualate excitotoxicity in hippocampal neurons.

Glutamate neurotoxicity is thought to play a role in the pathogenesis of several neurodegenerative diseases. While prolonged activation of either NMDA or non-NMDA receptors causes neuronal damage, NMDA receptors appear to mediate most of the glutamate toxicity. The reasons why NMDA toxicity predominates are uncertain but may relate to more effective neuroprotective mechanisms acting at non-NMDA receptors. To determine whether desensitization is one such mechanism, we studied the effects of the lectin wheat germ agglutinin (WGA) on quisqualate currents and toxicity in cultured postnatal rat hippocampal neurons. After WGA treatment, quisqualate currents exhibit little desensitization and a 4- to 8-fold increase in steady-state amplitude. WGA also markedly augments the degree of acute, quisqualate-induced neuronal degeneration. These results suggest that non-NMDA desensitization serves a neuroprotective function in hippocampal neurons.

Animals↗
PubMed1989

Calcium influx through N-methyl-D-aspartate channels activates a potassium current in postnatal rat hippocampal neurons.

Calcium-activated potassium conductances play important roles in modulating neuronal excitability. Indeed, the effects of some neurotransmitters such as acetylcholine and norepinephrine are, in part, due to actions on these conductances. We have found that the N-methyl-D-aspartate (NMDA) class of excitatory amino acid receptors also is coupled to a calcium activated potassium current. In voltage-clamped postnatal rat hippocampal neurons, NMDA responses consist of an initial inward cationic current followed by a slowly developing outward current carried by potassium ions. The slow outward current always follows the inward current, is associated with an increase in membrane conductance and is dependent on the influx of calcium ions. Similar responses are produced by other agonists active at NMDA receptors, including aspartate, glutamate and ibotenate, but are not activated by kainate, quisqualate or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA). Inhibition of the NMDA gated inward current by a competitive antagonist, 2-amino-5-phosphonovalerate (APV), eliminates the outward current. From these results we conclude that calcium influx through NMDA channels activates a potassium current. The extended time course of this outward current suggests that NMDA receptors may modulate neuronal excitability long after the opening of the NMDA channel.

Animals↗
PubMed1989

Role of excitatory amino acids in brain injury caused by hypoxia-ischemia, status epilepticus, and hypoglycemia.

Glutamate, the major excitatory neurotransmitter of the brain, mediates neuronal injury from hypoxia-ischemia, hypoglycemia, and status epilepticus. Drugs that block glutamate receptors, particularly the N-methyl-D-aspartate (NMDA) receptor, protect neurons from these insults. Noncompetitive antagonists of NMDA receptors have the potential to prevent perinatal neurologic morbidity.

Animals↗
PubMed1987

Blockade of excitatory amino acid receptors protects anoxic hippocampal slices.

Experiments in a variety of preparations have indicated that excessive activation of receptors for the excitatory amino acids glutamate and aspartate may mediate irreversible anoxic neuronal injury. We investigated this hypothesis in the in vitro hippocampal slice. Rat hippocampal slices perfused for 40 min with buffer equilibrated with 95% nitrogen/5% carbon dioxide lost their extracellular CA1 population spikes and failed to recover after prolonged reoxygeneration. It was impossible to locate cells with normal physiological properties in these anoxic slices with standard intracellular recording techniques. However, when excitatory transmission was blocked during anoxia with either high concentrations of magnesium or antagonists of excitatory amino acids (kynurenate or aminophosphonovalerate), the population spike returned to preanoxia levels. Intracellular recording showed that neurons in these protected slices had normal resting potentials, action potentials, and input resistances. These experiments provide additional support for the involvement of excitatory amino acids and their receptors in anoxic neuronal injury.

2-Amino-5-phosphonovalerate↗
PubMed1987

Ketamine protects hippocampal neurons from anoxia in vitro.

Ketamine, a dissociative, general anesthetic, blocks the excitation produced by activating one class of excitatory amino acid receptors, the N-methyl-D-aspartate receptor in the rat. We have found that ketamine can protect hippocampal neurons in culture and slice from anoxia. When added to cultures immediately prior to anoxic exposure, ketamine prevented the neuronal destruction seen after a day of anoxia. Neurons appeared undamaged and had normal resting and action potentials. Adenosine triphosphate levels in ketamine-protected anoxic cultures were approximately two-thirds of normal controls. Ketamine also prevented the irreversible loss of the population spike seen in hippocampal slices after prolonged perfusion with anoxic buffer. These results suggest that ketamine may have therapeutic potential in preventing anoxic damage from stroke in man.

Anesthesia, General↗
PubMed1984

Munchausen's syndrome by proxy (child abuse) presenting as apparent autoerythrocyte sensitization syndrome: an unusual presentation of Polle syndrome.

Munchausen's syndrome was initially described in 1951. It has become increasingly recognized since that time. Recently, Munchausen's syndrome by proxy or Polle syndrome has been described. In this disease entity, a parent causes a factitious disease in a child. The disease may require extensive medical testing and the result may even be death. A wide variety of presentations of Polle syndrome have been reported including cardiac arrest, recurrent sepsis, and factitious bleeding. Autoerythrocyte sensitization, a syndrome of spontaneous purpura, was initially described in 1955. The diagnostic test described is intradermal injection of autologous blood which produces an area of painful purpura. The syndrome is therefore postulated to be due to hypersensitivity in the patient's own RBCs. The majority of patients with autoerythrocyte sensitization have had psychiatric disorders and the symptoms have improved only with psychotherapy. An infant who had a clinical picture of autoerythrocyte sensitization and who was later found to be a victim of Polle syndrome is reported.

Autoimmune Diseases↗
PubMedDate not supplied

The analysis of cocaine and benzoylecgonine in meconium.

We describe an assay for measuring cocaine and benzoylecgonine in meconium of infants born to mothers suspected of using cocaine during their pregnancy. The assay involves the use of fluorescence polarization immunoassay (FPIA) to screen for benzoylecgonine in a methanolic extract of the meconium. The FPIA is sensitive to 0.6 microgram benzoylecgonine per gram meconium. Confirmation of the presence (or absence) of benzoylecgonine and cocaine in meconium samples was performed by solid phase extraction of a second methanolic extract of the meconium, derivatizing using BSTFA, followed by a gas chromatographic/mass spectrometric (GC/MS) analysis, which can detect both cocaine and benzoylecgonine. The GC/MS confirmation was sensitive to less than 0.25 microgram cocaine or 0.5 microgram benzoylecgonine per gram meconium. FPIA, which is commonly used in many toxicology laboratories, is advantageous because it precludes the need to use radioimmunoassays for the initial screen. The confirmation step provides greater certainty for the presence of cocaine and/or benzoylecgonine in meconium.

Cocaine↗