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Biomedical subjects

K Conley

Publications and source records attributed to K Conley.

11 recordsLinked to original sources

Comparing the subjective, psychomotor and physiological effects of intravenous nalbuphine and morphine in healthy volunteers.

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of nalbuphine in healthy non-drug abusing volunteers and to compare and contrast the effects of equianalgesic doses of nalbuphine and morphine. Subjects (12 males, 4 females) without histories of opiate dependence were injected in an upper extremity vein with 0, 2.5, 5.0 or 10 mg/70 kg nalbuphine, or with 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. The 10-mg doses of nalbuphine and morphine are considered equianalgesic and are doses commonly given for relief of postoperative pain. Subjective effects of nalbuphine included increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and the Lysergic Acid Diethylamide scale of the Addiction Research Center Inventory; increased adjective checklist ratings of "nodding," "numb" and "sweating"; increased visual analog scale ratings of "coasting or spaced out," "high" and "sleepy" and increased "feel drug effect" and drug-liking ratings. Ten milligrams of nalbuphine had subjective effects similar, and similar in magnitude, to those of 10 mg of morphine. Nalbuphine produced exophoria and impairment on the Digit Symbol Substitution Test in a dose-related fashion. Ten milligrams of morphine produced exophoria but did not affect performance on the Digit Symbol Substitution Test. Both nalbuphine and morphine induced miosis and decreases in respiration rate. The results of the present study demonstrate that 2.5 to 10 mg nalbuphine had orderly, dose-related effects on subjective, psychomotor and physiological variables. The results also indicate that 10 mg of nalbuphine produces a profile of subjective, psychomotor and physiological effects similar to that of an equianalgesic dose of morphine (10 mg). The similarity in profiles between drugs at this dose is consistent with both infrahuman studies, which suggests that nalbuphine is a mu agonist, and studies with nondependent opioid abusers, in which relatively low doses of nalbuphine (such as 10 mg) produce morphine-like effects.

Adult

Comparing the subjective, psychomotor and physiological effects of intravenous buprenorphine and morphine in healthy volunteers.

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of buprenorphine in nondrug-abusing volunteers and to compare and contrast the effects of equianalgesic doses of buprenorphine and morphine. Sixteen subjects without histories of opiate dependence were injected in an upper extremity vein with 0, 0.075, 0.15 or 0.3 mg/70 kg buprenorphine, or 10 mg/70 kg morphine, using a randomized, double-blind, cross-over design. The 0.3-mg buprenorphine dose and 10-mg morphine dose are considered to be equianalgesic and are doses commonly given for relief of postoperative pain. Buprenorphine increased scores on the Pentobarbital-Chlorpromazine-Alcohol Group scale and decreased scores on the Benzedrine Group scale of the Addiction Research Center Inventory, increased adjective checklist ratings of "nodding," "skin itchy," and "turning of stomach," and increased visual analogue scale ratings of "dizzy," "nauseous" and "sleepy." Buprenorphine (0.3 mg) in general had subjective effects of greater magnitude than that of 10 mg morphine. Buprenorphine produced impairment on five measures of psychomotor performance in a dose-related fashion. Ten mg morphine produced minimal psychomotor impairment. Both buprenorphine and morphine induced miosis, but buprenorphine (0.3 mg) had a larger and longer effect than that of 10 mg morphine. Buprenorphine, but not morphine, decreased respiration rate. The results of our study demonstrate that 0.075 to 0.3 mg buprenorphine had orderly, dose-related effects on subjective, psychomotor and physiological variables. Further, a clinically relevant dose of buprenorphine, 0.3 mg, produced a greater magnitude of subjective and psychomotor-impairing effects than did an equianalgesic dose of morphine.

Adult

Structural correlates of speed and endurance in skeletal muscle: the rattlesnake tailshaker muscle

The western diamondback rattlesnake Crotalus atrox can rattle its tail continuously for hours at frequencies approaching 90 Hz. We examined the basis of these fast sustainable contractions using electromyography, data on oxygen uptake and the quantitative ultrastructure of the tailshaker muscle complex. The tailshaker muscle has no apparent unique structures; rather, the relative proportions of the structures common to all skeletal muscles appear to be present (1) to minimize activation, contraction and relaxation times via an extremely high volume density of sarcoplasmic reticulum (26 %) as well as, (2) to maximize ATP resysnthesis via a high volume density of mitochondria (26 %). The high rate of ATP supply is reflected in the in vivo muscle mass-specific oxygen uptake of this group of muscles which, at 585 ml O2 kg-1 min-1 during rattling at 30 °C body temperature, exceeds that reported for other ectotherm and many endotherm muscles. Since the change in oxygen uptake paralleled that of the rattling frequency over the range of measured body temperatures, there was a nearly constant O2 cost per muscle contraction (0.139±0.016 µl O2 g-1). Electromyo-graphic analysis suggests that each of the six muscles that make up the shaker complex may be a single motor unit. Finally, the maximum rate of mitochondrial oxygen uptake is similar to that of various mammals, a hummingbird, a lizard, an anuran amphibian and of isolated mitochondria (at 10 000-40 000 molecules O2 s-1 µm2 of cristae surface area, when normalized to 30 °C), suggesting a shared principle of design of the inner mitochondrial membrane among the vertebrates.

Journal Article

Phenol red is a thromboxane A2/prostaglandin H2 receptor antagonist in canine lingual arteries and human platelets.

Phenol red (PR) is used as a pH indicator in cell culture medium. We found that cell culture medium containing PR relaxed canine lingual arteries (LA) contracted by the thromboxane A2/prostaglandin endoperoxide (TPE) receptor agonist (15S)-hydroxy-11-alpha-9-alpha- (epoxymethano)prosta-5Z,13E-dienoic acid (U46619). We tested the effect of PR and the TPE receptor antagonist ONO-3708 on U46619, prostaglandin F2 alpha (PGF2 alpha), phenylephrine (PE) and potassium chloride (KCl)-induced contraction of the LA and on human platelet aggregation to U46619, ADP, arachidonic acid (AA), A23187 and thrombin. U46619, PGF2 alpha, KCl and PE produced equal tension development of the LA. PR relaxed the LA contracted with U46619 and PGF2 alpha with IC50 concentrations of 18.3 +/- 10 and 37.3 +/- 8.8 microM, respectively. ONO-3708 inhibited the contractions to U46619 and PGF2 alpha with IC50 of 9.4 +/- 2.2 and 12.2 +/- 2.2 nM, respectively. However, PR (300 microM) and ONO-3708 (300 nM) did not affect contraction of the LA to KCl or PE. PR inhibited human platelet aggregation, in vitro, to AA and U46619 and second wave aggregation to ADP but did not affect thrombin or first wave ADP-mediated platelet aggregation. PR inhibited U46619 and AA-induced changes in cyclic AMP and Fura-2 calcium transients in platelets and LA. However, PR did not affect the activation of cyclic AMP or intracellular calcium ion in platelets or calcium influx and the release of intracellular calcium ion in canine LA produced by ryanodine, KCl and PE. The concentration of PR in many culture media is between 40 and 70 microM. The data support the conclusion that PR, in concentrations used as a pH indicator, is a selective antagonist of TPE receptors.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5

Sequence of the clathrin heavy chain from Saccharomyces cerevisiae and requirement of the COOH terminus for clathrin function.

The sequence of the clathrin heavy chain gene, CHC1, from Saccharomyces cerevisiae is reported. The gene encodes a protein of 1,653 amino acids that is 50% identical to the rat clathrin heavy chain (HC) (Kirchhausen, T., S. C. Harrison, E. P. Chow, R. J. Mattaliano, R. L. Ramachandran, J. Smart, and J. Brosius. 1987. Proc. Natl. Acad. Sci. USA. 84:8805-8809). The alignment extends over the complete length of the two proteins, except for a COOH-terminal extension of the rat HC and a few small gaps, primarily in the globular terminal domain. The yeast HC has four prolines in the region of the rat polypeptide that was proposed to form the binding site for clathrin light chains via an alpha-helical coiled-coil interaction. The yeast protein also lacks the COOH-terminal Pro-Gly rich segment present in the last 45 residues of the rat HC, which were proposed to be involved in the noncovalent association of HCs to form trimers at the triskelion vertex. To examine the importance of the COOH terminus of the HC for clathrin function, a HC containing a COOH-terminal deletion of 57 amino acids (HC delta 57) was expressed in clathrin-deficient yeast (chc1-delta). HC delta 57 rescued some of the phenotypes (slow growth at 30 degrees, genetic instability, and defects in mating and sporulation) associated with the chc1-delta mutation to normal or near normal. Also, truncated HCs were assembled into triskelions. However, cells with HC delta 57 were temperature sensitive for growth and still displayed a major defect in processing of the mating pheromone alpha-factor. Fewer coated vesicles could be isolated from cells with HC delta 57 than cells with the wild-type HC. This suggests that the COOH-terminal region is not required for formation of trimers, but it may be important for normal clathrin-coated vesicle structure and function.

Amino Acid Sequence

Genetic instability of clathrin-deficient strains of Saccharomyces cerevisiae.

Saccharomyces cerevisiae strains carrying a mutation in the clathrin heavy chain gene (CHC1) are genetically unstable and give rise to heterogeneous populations of cells. Manifestations of the instability include increases in genome copy number as well as compensatory genetic changes that allow better growing clathrin-deficient cells to take over the population. Increases in genome copy number appear to result from changes in ploidy as well as alterations in normal nuclear number. Genetic background influences the frequency at which cells with increased genome content are observed in different Chc- strains. We cannot distinguish whether genetic background affects the rate at which aberrant nuclear division events occur or a growth advantage of cells with increased nuclear and/or genome content. However, survival of chc1-delta cells does not require an increase in genome copy number. The clathrin heavy chain gene was mapped 1-2 cM distal to KEX1 on the left arm of chromosome VII by making use of integrated 2 mu plasmid sequences to destabilize distal chromosome segments and allow ordering of the genes.

Canavanine

Endurance training in humans: aerobic capacity and structure of skeletal muscle.

The adaptation of muscle structure, power output, and mass-specific rate of maximal O2 consumption (VO2max/Mb) with endurance training on bicycle ergometers was studied for five male and five female subjects. Biopsies of vastus lateralis muscle and VO2max determinations were made at the start and end of 6 wk of training. The power output maintained on the ergometer daily for 30 min was adjusted to achieve a heart rate exceeding 85% of the maximum for two-thirds of the training session. It is proposed that the observed preferential proliferation of subsarcolemmal vs. interfibrillar mitochondria and the increase in intracellular lipid deposits are two possible mechanisms by which muscle cells adapt to an increased use of fat as a fuel. The relative increase of VO2max/Mb (14%) with training was found to be smaller by more than twofold than the relative increase in maximal maintained power (33%) and the relative change in the volume density of total mitochondria (+40%). However, the calculated VO2 required at an efficiency of 0.25 to produce the observed mass-specific increase in maximal maintained power matched the actual increase in VO2max/Mb (8.0 and 6.5 ml O2 X min-1 X kg-1, respectively). These results indicate that despite disparate relative changes the absolute change in aerobic capacity at the local level (maintained power) can account for the increase in aerobic capacity observed at the general level (VO2max).

Adipose Tissue

Comparison of oral feeding of peptide and amino acid meals to normal human subjects.

Intestinal perfusion studies performed in man have suggested that amino acid nitrogen may be absorbed more rapidly from peptides than free amino acids. The aim of the present study was to compare the effects of the oral administration of peptides and free amino acids. Two isonitrogenous liquid test meals, one containing 50 g of a partial enzymic hydrolysate of fish protein in which approximately 80% of the nitrogen content was present as small peptides (peptide meal), and the other a mixture of free amino acids (amino acid meal) the composition and molar pattern of which simulated that of the peptide meal, were administered on separate occasions to six normal subjects intubated with a triple lumen tube. Both meals contained the reference marker polyethylene glycol. Fractional absorption of amino acid residues one and two hours after ingestion of the two meals was similar at three intestinal locations situated 120, 160, and 200 cm from the mouth of each subject, and at two hours 73.8% and 72.0% of the amino acid residues had been absorbed respectively by the time the contents of the peptide and amino acid meals reached the middle sampling port of the tube. The total sum of individual amino acid increments in plasma was significantly greater 30 minutes (p < 0.025) and one hour (p < 0.05) after ingestion of the peptide than amino acid meals. By three hours the total area under the two plasma curves was similar. Normal human subjects thus appeared to be capable of assimilating orally administered mixtures of peptides and free amino acids with equal efficiency. Secretion of fluid into the lumen of the upper small intestine, assessed by reference to dilution of the polyethylene glycol, was less after ingestion of the peptide meal. In clinical situations characterised by fluid and electrolyte malabsorption consideration might be given to using small peptides rather than free amino acids as the nitrogen source in nutritional diets.

Adult

Cyanide ingestion: preventing the cascade.

Patients with cyanide exposure present a rare and unique challenge to the critical care nurse. The following article assists the critical care nurse and advanced practice nurse in understanding the pathophysiology of cyanide exposure, assessment of signs and symptoms, and antidotal and supportive therapies. In addition, a case review of nursing care for a patient exposed to cyanide is discussed.

Antidotes