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Biomedical subjects

C W Myers

Publications and source records attributed to C W Myers.

At least 19 recordsLinked to original sources

A model for the genesis of arterial pressure Mayer waves from heart rate and sympathetic activity.

Both theoretic models and cross-spectral analyses suggest that an oscillating sympathetic nervous outflow generates the low-frequency arterial pressure fluctuations termed Mayer waves. Fluctuations in heart rate also have been suggested to relate closely to Mayer waves, but empiric models have not assessed the joint causative influences of heart rate and sympathetic activity. Therefore, we constructed a model based simply upon the hemodynamic equation derived from Ohm's Law. With this model, we determined time relations and relative contributions of heart rate and sympathetic activity to the genesis of arterial pressure Mayer waves. We assessed data from eight healthy young volunteers in the basal state and in a high sympathetic state known to produce concurrent increases in sympathetic nervous outflow and Mayer wave amplitude. We fit the Mayer waves (0.05-0.20 Hz) in mean arterial pressure by the weighted sum of leading oscillations in heart rate and sympathetic nerve activity. This model of our data showed heart rate oscillations leading by 2-3.75 s were responsible for almost half of the variance in arterial pressure (basal R2 = 0.435 +/- 0.140, high sympathetic R2= 0.438 +/- 0.180). Surprisingly, sympathetic activity (lead 0-5 s) contributed only modestly to the explained variance in Mayer waves during either sympathetic state (basal: delta R2 = 0.046 +/- 0.026; heightened: delta R2 = 0.085 +/- 0.036). Thus, it appears that heart rate oscillations contribute to Mayer waves in a simple linear fashion, whereas sympathetic fluctuations contribute little to Mayer waves in this way. Although these results do not exclude an important vascular sympathetic role, they do suggest that additional factors, such as sympathetic transduction into vascular resistance, modulate its influence.

Adult↗

Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans.

Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

Adrenergic beta-Antagonists↗

The resonant dynamics of speech perception: interword integration and duration-dependent backward effects.

How do listeners integrate temporally distributed phonemic information into coherent representations of syllables and words? For example, increasing the silence interval between the words "gray chip" may result in the percept "great chip," whereas increasing the duration of fricative noise in "chip" may alter the percept to "great ship" (B. H. Repp, A. M. Liberman, T. Eccardt, & D. Pesetsky, 1978). The ARTWORD neural model quantitatively simulates such context-sensitive speech data. In ARTWORD, sequentially stored phonemic items in working memory provide bottom-up input to unitized list chunks that group together sequences of items of variable length. The list chunks compete with each other. The winning groupings feed back to establish a resonance which temporarily boosts the activation levels of selected items and chunks, thereby creating an emergent conscious percept whose properties match such data.

Cues↗

Mechanisms underlying very-low-frequency RR-interval oscillations in humans.

BACKGROUND: Survival of post-myocardial infarction patients is related inversely to their levels of very-low-frequency (0.003 to 0.03 Hz) RR-interval variability. The physiological basis for such oscillations is unclear. In our study, we used blocking drugs to evaluate potential contributions of sympathetic and vagal mechanisms and the renin-angiotensin-aldosterone system to very-low-frequency RR-interval variability in 10 young healthy subjects. METHODS AND RESULTS: We recorded RR intervals and arterial pressures during three separate sessions, with the patient in supine and 40 degree upright tilt positions, during 20-minute frequency (0.25 Hz) and tidal volume-controlled breathing after intravenous injections: saline (control), atenolol (0.2 mg/kg, beta-adrenergic blockade), atropine sulfate (0.04 mg/kg, parasympathetic blockade), atenolol and atropine (complete autonomic blockade), and enalaprilat (0.02 mg/kg, ACE blockade). We integrated fast Fourier transform RR-interval spectral power at very low (0.003 to 0.03 Hz), low (0.05 to 0. 15 Hz), and respiratory (0.2 to 0.3 Hz) frequencies. Beta-adrenergic blockade had no significant effect on very-low- or low-frequency RR-interval power but increased respiratory frequency power 2-fold. ACE blockade had no significant effect on low or respiratory frequency RR-interval power but modestly (approximately 21%) increased very-low-frequency power in the supine (but not upright tilt) position (P<0.05). The most profound effects were exerted by parasympathetic blockade: Atropine, given alone or with atenolol, abolished nearly all RR-interval variability and decreased very-low-frequency variability by 92%. CONCLUSIONS: Although very-low-frequency heart period rhythms are influenced by the renin-angiotensin-aldosterone system, as low and respiratory frequency RR-interval rhythms, they depend primarily on the presence of parasympathetic outflow. Therefore the prognostic value of very-low-frequency heart period oscillations may derive from the fundamental importance of parasympathetic mechanisms in cardiovascular health.

Adult↗

First occurrence of tetrodotoxin in a dendrobatid frog (Colostethus inguinalis), with further reports for the bufonid genus Atelopus.

The water-soluble toxin present in skin of Colostethus inguinalis (Dendrobatidae) was identified as tetrodotoxin by fluorometric HPLC analysis. The amount of tetrodotoxin per frog skin was estimated by HPLC, mouse toxicity, and inhibition of [3H]saxitoxin binding to brain membranes as 0.1 to 1.2 micrograms. Small amounts of anhydrotetrodotoxin and 4-epietrodotoxin also were present. Tetrodotoxin-like activity was not detected by inhibition of [3H]saxitoxin binding in other species of Colostethus nor in other dendrobatids (Aromobates, Dendrobates, Phyllobates). Tetrodotoxin-like activity was present in extracts of skin of five species of Atelopus (Bufonidae). HPLC analysis identified tetrodotoxin as the major toxic component in Atelopus spumarius and A. varius, as a minor component in A. spurrelli, and as a trace component in A. ignescens and A. zeteki. The major tetrodotoxin-like compounds in the last three species were not identified. Tetrodotoxin-like activity was not detected by inhibition of [3H]saxitoxin binding in skin extracts from three other genera of bufonids.

Amphibian Venoms↗

Effect of polyol molecular weight on the physical properties and haemocompatibility of polyurethanes containing polyethylene oxide macroglycols.

The physical properties and haemocompatibility of polyurethanes containing polyethylene oxide (PEO) of varying molecular weights but constant weight fraction of hard segment are investigated. The PEO molecular weights studied were 600, 1450 and 8000. Analysis of polyurethane phase separation and crystallinity using dynamic-mechanical analysis and differential scanning calorimetry show that the degree of phase separation and crystallinity increase with polyol molecular weight, but level off at the highest molecular weights. The degree of water absorption increases substantially with increasing PEO molecular weight, levelling off at the highest molecular weight. Tensile data show a maximum in extensibility at a polyethylene glycol (PEG) molecular weight of 1450, while ultimate strength increases with increasing segment length. When the materials are hydrated, there is a significant drop in the modulus, ultimate stress and ultimate elongation. Dynamic contact angle measurements show that surface hydrophobicity decreases as the soft segment molecular weight increases. Using electron spectroscopy for chemical analysis (ESCA) to determine the surface composition of these polyurethanes, it was found that the hard segment content at the surface increases as the polyol block length decreases. The haemocompatibility of these polyurethanes was investigated in an ex vivo canine blood-contacting model. Only for the shortest block length studied, PEG-600, are differences in blood compatibility observed. This material was found to be the most thrombogenic. The PEG-1450 sample shows comparable blood compatibility to PEG-8000.

Animals↗

Postoperative complications in patients receiving suramin therapy.

BACKGROUND: Suramin is an antiparasitic agent that is currently being evaluated for antineoplastic activity. Documented toxicities of suramin include adrenal and renal insufficiency, coagulation factor abnormalities, immunosuppression, and polyneuropathy. These adverse effects have potential for contributing to postoperative morbidity in surgical patients. Because no experience with suramin has been reported in the surgical literature, this 5-year retrospective review of postoperative complications in patients receiving suramin was performed. METHODS: From a review of 171 charts, 14 patients were identified who had undergone a major surgical procedure either while receiving intravenous suramin or within 1 year after its administration. Primary diagnoses included prostate cancer (six), lymphoma (four), ovarian cancer (two), colon cancer (one), and glioblastoma (one). All patients received replacement dose hydrocortisone at the initiation of suramin therapy and thereafter. RESULTS: Eighteen major surgical procedures were performed with 18 complications occurring in five patients. The predominant complications encountered were hemorrhage (five), impaired wound healing (three), and bowel dysmotility (two). A highly significant relationship existed between the incidence of complications and interval from completion of suramin therapy to the time of operation (p < 0.0005), with 17 of the 18 morbidities occurring within the first month. The length of operation (p < 0.05) and amount of blood transfused during the procedure were related to postoperative morbidity (p < 0.05). No other factors evaluated were correlated to complications. CONCLUSIONS: This experience suggests the avoidance of elective procedures during the first month after suramin therapy and a heightened awareness of the potential for bleeding and wound healing problems in patients receiving suramin who do require an emergent procedure.

Adult↗

Frog secretions and hunting magic in the upper Amazon: identification of a peptide that interacts with an adenosine receptor.

A frog used for "hunting magic" by several groups of Panoan-speaking Indians in the borderline between Brazil and Peru is identified as Phyllomedusa bicolor. This frog's skin secretion, which the Indians introduce into the body through fresh burns, is rich in peptides. These include vasoactive peptides, opioid peptides, and a peptide that we have named adenoregulin, with the sequence GLWSKIKEVGKEAAKAAAKAAGKAALGAVSEAV as determined from mass spectrometry and Edman degradation. The natural peptide may contain a D amino acid residue, since it is not identical in chromatographic properties to the synthetic peptide. Adenoregulin enhances binding of agonists to A1 adenosine receptors; it is accompanied in the skin secretion by peptides that inhibit binding. The vasoactive peptide sauvagine, the opioid peptides, and adenoregulin and related peptides affect behavior in mice and presumably contribute to the behavioral sequelae observed in humans.

Amino Acid Sequence↗

One-dimensional and two-dimensional 1H- and 13C-nuclear magnetic resonance (NMR) analysis of vitamin E raw materials or analytical reference standards.

Two-dimensional spectral analysis (COSY, HETCOR) was utilized to make the complete 13C- and 1H-NMR assignments for alpha-, beta-, gamma-, and delta-tocopherol as well as for the acetate and succinate esters of alpha-tocopherol. 13C-NMR was found to be especially useful in distinguishing between the various tocopherols and distinguishing between the d-isomer and the d,l-racemic mixture. HETCOR spectra were also found to be useful for the qualitative identification of mixtures of the tocopherols and sesame oil. Using a procedure designed to minimize errors arising from spin relaxation and nuclear Overhauser effects, 13C-NMR peak integrals were used to quantitate alpha-tocopherol and delta-tocopherol in the presence of sesame oil using benzoic acid as the standard for calibration of the quantitation. The NMR results were compared to a capillary column gas chromatographic analysis of the individual alpha-tocopherol and delta-tocopherol reference materials.

Carbon Isotopes↗

Tryptophan toxicity: a pharmacoepidemiologic review of eosinophilia-myalgia syndrome.

Tryptophan, an essential amino acid commercially available as a dietary supplement, has been implicated in the development of a new and potentially fatal clinical entity: eosinophilia-myalgia syndrome (EMS). EMS reached epidemic proportions in the US in late 1989 and early 1990, with 1536 cases and 27 deaths reported as of August 1990. Features of the syndrome include intense, debilitating myalgias and marked peripheral eosinophilia. Vasculitis, neuropathy, and pulmonary involvement also may be observed but are not pathognomonic. Death typically ensues from ascending polyneuropathy with resulting paralysis and respiratory arrest. Treatment involves discontinuation of tryptophan ingestion. Administration of prednisone may not always alleviate or reverse the symptoms. Recovery is generally slow. The etiology of EMS has been traced to a contaminant in the bulk manufacturing process of tryptophan by a single Japanese company. Efforts are currently underway to confirm the structure of the contaminant by laboratory synthesis and to define its biologic and toxic effects using an animal model for EMS.

Eosinophilia-Myalgia Syndrome↗

Further classification of skin alkaloids from neotropical poison frogs (Dendrobatidae), with a general survey of toxic/noxious substances in the amphibia.

Cutaneous granular glands are a shared character of adult amphibians, including caecilians, and are thought to be the source of most biologically active compounds in amphibian skin. Data are available from one or more species in over 100 of nearly 400 genera comprising the three living orders of Amphibia. Many species contain unidentified substances judged to be noxious based on predator aversion or human taste. Additionally, there is a great diversity of known compounds, some highly toxic as well as noxious, which can be tabulated under four broad categories: biogenic amines, peptides, bufodienolides (bufogenins) and alkaloids. The last category includes alkaloids derived from biogenic amines, water-soluble alkaloids (tetrodotoxins) and lipophilic alkaloids. Most compounds are known only from skin of adult amphibians, but the toxic and noxious properties of eggs and larvae of certain salamanders and toads can be attributed to tetrodotoxins and bufodienolides, which occur also in adult tissues other than skin. Predator aversion and various antipredator behaviors and aposematic colorations clearly prove the defensive value of these diverse metabolites, whether or not they are elaborated primarily (e.g. alkaloids) or secondarily (e.g. some peptides and biogenic amines) for this function. Lipophilic alkaloids include the samandarine alkaloids, known definitely only from an Old World genus of salamanders, and the more than 200 dendrobatid alkaloids. Nearly all the latter are unique to neotropical poison frogs of the genera Dendrobates and Phyllobates (Dendrobatidae), except for seemingly homoplastic occurrences of a few such alkaloids in small brightly colored anurans of several other families. Owing to recent discoveries and new structural information, the dendrobatid alkaloids are here partitioned among the following major and minor classes: batrachotoxins, histrionicotoxins, indolizidines, pumiliotoxin-A class and its allopumiliotoxin and homopumiliotoxin subclasses, decahydroquinolines, gephyrotoxins, 2,6-disubstituted piperidines, 2,5-disubstituted pyrrolidines, pyridyl-piperidines, indole alkaloids, azatricyclododecenes and amidine alkaloids. Except for the steroidal batrachotoxins, and the minor classes of pyrrolidine alkaloids, indole alkaloids and amidine alkaloids, all the above contain a piperidine ring. A large number of piperidine-based alkaloids occur mainly as trace compounds in Dendrobates and remain unclassified; the only water-soluble toxin so far discovered in a dendrobatid (Colostethus) is structurally unknown, but conceivably an alkaloid.

Alkaloids↗

Occurrence of skin alkaloids in non-dendrobatid frogs from Brazil (Bufonidae), Australia (Myobatrachidae) and Madagascar (Mantellinae).

Several taxa of small frogs from the southern hemisphere contain alkaloids similar or identical to compounds previously known only from neotropical poison frogs of the family Dendrobatidae. Skin of the Brazilian toad Melanophryniscus moreirae (family Bufonidae) contains a new alkaloid 8-hydroxy-8-methyl-6-(5'-hydroxy-2'-methyl-hexylidene)-1-azabicycl o-[4.3.0] nonane (C16H29NO2), which is designated pumiliotoxin 267C. Such a structure is typical of the pumiliotoxin-A class of dendrobatid alkaloids. Melanophyryniscus moreirae contains smaller quantities of an alkaloid (C19H33NO3) identical in chromatographic and mass spectral properties to the dendrobatid alkaloid allopumiliotoxin 323B. Allopumiliotoxin 323B and an isomer of 267C occur with unidentified alkaloids in skin of the Australian frog Pseudophryne semimarmorata (family Myobatrachidae) and also in the skin of the Madagascan frog Mantella aurantiaca (family Ranidae, subfamily Mantellinae). In addition to new compounds, Mantella aurantiaca and M. madagascariensis also contain other alkaloids (e.g. histrionicotoxin and pumiliotoxin B) that were known previously only in dendrobatid frogs. Such alkaloids have not been detected in a phylogenetically wide array of other anuran amphibians, and the dendrobatid alkaloids thus become an evolutionary enigma. Certain of these compounds may have arisen convergently from new biosynthetic pathways in several families of frogs, or these alkaloids may represent parallel expression of shared-primitive pathways that are unexpressed or lost in related frogs.

Alkaloids↗

Dart-poison frogs.

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Amphibian Venoms↗

Levels of batrachotoxin and lack of sensitivity to its action in poison-dart frogs (Phyllobates).

Batrachotoxin is present in remarkably high amounts in the skin of Phyllobates terribilis. Levels of batrachotoxin tend to be reduced when P. terribilis is maintained in captivity, but even after being confined for up to 6 years, these frogs were still at least five times more toxic than other Phyllobates species used by natives for poisoning blowgun darts. Batrachotoxin was not detectable in F1 progeny reared to maturity in captivity. Nerve and muscle preparations from wild-caught frogs and from the nontoxic F1 frogs were both insensitive to batrachotoxin. The regulatory site controlling sodium-channel activation and permeability appears to have been minimally altered to prevent interaction with batrachotoxin, but is still sensitive to other sodium conductance activators (veratridine, grayanotoxin) to which the frogs arenot exposed naturally.

Age Factors↗

Widespread occurrence in frogs and toads of skin compounds interacting with the ouabain site of Na+, K+-ATPase.

Amphibians of the family Bufonidae contain high levels of skin compounds that both inhibit Na+- and K+-dependent adenosinetriphosphatase and antagonize the binding of ouabain to the enzyme. In species of Bufo and Atelopus, these compounds are relatively nonpolar bufodienolides, whereas Dendrophryniscus and Melanophryniscus contain more polar compounds of unknown structure. Skin extracts from 30 of 48 species of frogs representing an additional eight families contained relatively low levels of compounds that inhibit binding of ouabain to Na+,K+-adenosinetriphosphatase. The widespread occurrence of low levels of inhibitory compounds is consonant with the role for these compounds as physiological regulators of Na+,K+-adenosinetriphosphatase in amphibian skin; high levels in the Bufonidae probably also serve as a defense against some predators.

Animals↗