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PubMedDate not supplied

Use of noninvasive hemodynamics to aid decision making in the initiation and titration of neurohormonal agents.

Angiotensin-converting enzyme inhibitors, beta adrenergic blockers, and nesiritide are pharmacologic agents for heart failure with both short- and long-term neurohormonal and hemodynamic effects. Angiotensin-converting enzyme inhibitors and beta adrenergic blockers reduce morbidity and mortality in chronic heart failure. Higher doses may result in better outcomes than lower doses, but concern about hemodynamic tolerance is a major barrier to the initiation and up-titration of these agents. Nesiritide is a newer neurohormonal agent with proven efficacy and safety for use in decompensated heart failure, but appropriate patient selection has been challenging for clinicians. Like vasodilators, nesiritide may be underutilized in heart failure treatment. Impedance cardiography is a newer, noninvasive monitoring technology that can accurately measure hemodynamic parameters. Impedance cardiography is being used with increasing frequency by clinicians to guide therapy in patients with heart failure and has been proposed in heart failure treatment algorithms. Three case reports are presented to illustrate how hemodynamic data using impedance cardiography can be utilized in the initiation and titration of neurohormonal agents.

Adrenergic beta-Antagonists↗
PubMed1998

Radiofrequency catheter ablation of septal accessory pathways within the triangle of Koch: importance of energy titration testing other than the local electrogram characteristics for identifying the successful target site.

Radiofrequency (RF) catheter ablation of accessory atrioventricular (AV) connections in the proximity of His bundle or AV node is at high risk of developing complete heart block. A safe and effective protocol has not been well established. Nineteen consecutive patients with 19 septal accessory pathways within the triangle of Koch underwent a protocol with power-titrated RF energy testing to identify the target site for successful catheter ablation. At every potential target site preselected by local electrogram characteristics, RF energy was started at 5 W for 10 seconds, with an increment of 5 W (duration remained at 10 s) until maximally 30 W or the observation of transient interruption of accessory pathway conduction. By this stepwise RF energy testing, we successfully localized and ablated 18 (94.7%) of the 19 septal accessory pathways, 10 close to His bundle (zone I) and 8 away from it (zone II). The test-effective RF power was 20 W or less in 9 of all 11 septal accessory pathways in zone I, and 5 of the 8 in zone II (P = 0.68). Meanwhile, the final RF power for successful ablation was 30 W or less in 9 of the 10 zone I and 6 of the 8 zone II septal accessory pathways (P = 0.83). One patient with an accessory pathway in zone I was complicated with complete AV block after final ablation at 30 W. None of the local electrogram characteristics except continuous electrical activity during retrograde mapping was helpful in the prediction of ablation outcome. Careful RF energy titration testing could effectively help identify the target site for successful RF catheter ablation of septal accessory pathways within the triangle of Koch. The dependence on local electrogram manifestations could be frustrated by a low probability of success.

Adult↗
PubMed1996

Randomized comparison of two techniques for titrating power during radiofrequency ablation of accessory pathways.

INTRODUCTION: The purpose of this study was to prospectively compare the value of impedance and temperature monitoring during accessory pathway ablation. Temperature and impedance monitoring can be used during radiofrequency ablation of accessory pathways to titrate power to achieve adequate but not excessive tissue heating. METHODS AND RESULTS: One hundred thirty-two patients with a single accessory pathway were randomly assigned to undergo ablation using either impedance monitoring or temperature monitoring. During impedance monitoring, the endpoint for titration of power was a 5- to 10-omega decrease in the measured impedance while for temperature monitoring the endpoint was to achieve a temperature of 58 degrees to 62 degrees C. Two protocols were used. In protocol 1 (90 patients), impedance monitoring was performed with a nonthermistor catheter and temperature monitoring was performed with a thermistor catheter. In protocol 2 (42 patients), a thermistor catheter was used in all patients. In protocol 1, the success rate (93% vs 93%; P = 1.0), ablation procedure duration (57 +/- 56 vs 41 +/- 41 min), fluoroscopy time (48 +/- 29 vs 41 +/- 23 min; P = 0.3), number of applications (6.2 +/- 4.7 vs 5.7 +/- 4.6; P = 0.8), and the number of applications associated with coagulum formation (0.1 +/- 0.3 vs 0.3 +/- 0.6; P = 0.1) were similar in the two groups. In protocol 2, as in protocol 1, there were no differences in the success rate (91% vs 95%; P = 1.0), ablation procedure duration (49 +/- 37 vs 62 +/- 55 min; P = 0.4), fluoroscopy time (46 +/- 24 vs 49 +/- 36 min; P = 0.8), number of applications (6.8 +/- 7.0 vs 7.8 +/- 12.1; P = 0.7), or number of applications associated with coagulum formation (0.3 +/- 0.6 vs 0.2 +/- 0.7; P = 0.6), between the impedance and temperature monitoring groups. CONCLUSION: Temperature and impedance monitoring are equally effective in optimizing the results of accessory pathway ablation.

Adult↗
PubMed2005

Interaction of gymnemic acid with cyclodextrins analyzed by isothermal titration calorimetry, NMR and dynamic light scattering.

The physiological phenomenon that the antisweet taste effect of gymnemic acid (GA) is diminished by application of gamma-cyclodextrin (gamma-CD) to the mouth was evaluated at the molecular level using isothermal titration calorimetry, NMR and dynamic light scattering. These analyses showed that GA specifically binds to gamma-CD. Thermodynamic analysis using isothermal titration calorimetry revealed that the association constant of GA and gamma-CD is 10(5)-10(6) m(-1) with favorable enthalpy and entropy changes. The heat capacity change was negative and large, despite the change in accessible surface area upon binding being small. These thermodynamics indicate that the binding is dominated by hydrophobic interactions, which is in agreement with inclusion complex formation of gamma-CD. In addition, NMR measurements showed that in solution the spectra of GA are broad and sharpened by the addition of gamma-CD, indicating that unbound GA is in a water-soluble aggregate that is dispersed when it forms a complex with gamma-CD. Dynamic light scattering showed that the average diameter of unbound GA is > 30 nm and that of GA and gamma-CD complex is 2.2 nm, similar to unbound gamma-CD, supporting the aggregate property of GA and the inclusion complexation of GA by gamma-CD.

Calorimetry↗
PubMed2004

Prolonged pre-procedure fasting time is unnecessary when using titrated intravenous ketamine for paediatric procedural sedation.

BACKGROUND: Paediatric procedural sedation (PPS) is a common procedure in most general EDs. Many departmental guidelines suggest mandatory fasting times for children undergoing PPS, in an attempt to decrease the incidence of postoperative vomiting and (theoretically) aspiration pneumonitis, despite there being little or no evidence in the literature to support these mandatory fasting times. OBJECTIVES: To prospectively address the relationship between preprocedure fasting time and intraprocedure or postprocedure vomiting in children aged 1-12 years undergoing procedural sedation with intravenous ketamine in the ED. METHODS: From January 1999 to May 2000 all children presenting to the Royal Darwin Hospital Emergency Department with a condition requiring ketamine PPS were enrolled for data collection after parental consent was obtained. Titrated intravenous ketamine was administered via protocol. Prospective ED procedural sedation data collection forms of 272 consecutive cases of titrated intravenous ketamine sedation were reviewed. RESULTS: Fasting time was accurately recorded on 257 (95%) data collection forms. There was no intraprocedure vomiting. Overall rate of postprocedure vomiting was 13.9%. No statistically significant association between decreased fasting time and increased incidence of vomiting was found. In fact, there was a trend towards increased incidence of vomiting with increased fasting time (P = 0.08). The rate of vomiting of those children fasted 3 h or greater preprocedure (20/127 or 15.8%) was over twice the rate of those fasted less than 1 hour (2/30 or 6.6%). Incidence of vomiting was significantly associated with increasing age (P = 0.0007). No clinically evident aspiration pneumonitis occurred. CONCLUSION: Prolonged preprocedure fasting time did not reduce the incidence of postprocedure vomiting in this case series; to the contrary there was a increased incidence of vomiting with longer fasting times (P = 0.08). There was an increase in postprocedure vomiting with increasing age of the patients.

Age Distribution↗
PubMed2001

A comparison of coulometric titration and potentiometric determination of chloride concentration in rumen fluid.

The concentration of chloride ions in rumen fluid is a useful measure of obstructive gastrointestinal disease in ruminants and camelids. However, rumen fluid is very different from other biological fluids in its bacterial populations, consistency, and concentrations of various anions. Two methods of determining the chloride concentration in biological fluids were compared using centrifuged and filtered rumen fluid containing different amounts of sodium chloride. Although coulometric titration and potentiometric electrode analysis yielded results that had a strong linear relationship, the results of potentiometry were consistently and significantly higher, by about 20 mEq/L. This difference was investigated further by analyzing a series of fluids containing different concentrations of sodium acetate. Acetate was detected as chloride (0.21 chloride molecules per acetate molecule) by potentiometry but not by coulometric titration. Therefore, the acetate concentration of rumen fluid was the most likely cause of the discrepancy between tests in the original trial. In conclusion, the coulometric procedure may be more accurate than the potentiometric procedure for measuring rumen chloride when the concentrations of possible confounding ions are unknown.

Journal Article↗
PubMed1960

Nonlogarithmic linear titration curves.

Titration curves can be based on linear nonlogarithmic forms of the equilibrium equation of a dissociation reaction. From such curves, in contrast to those based on logarithmic transformations, both the end point of the titration and the dissociation constant can be derived.

Chemistry Techniques, Analytical↗
PubMed1963

SPECTROPHOTOMETRIC TITRATIONS OF HUMAN SERUM ALBUMIN AND REDUCED CARBOXYMETHYLATED ALBUMIN.

The tyrosyl groups of reduced and carboxymethylated human serum albumin, in which all disulfide bonds are broken, ionize at lower pH than those of native albumin, in spite of the greater negative charge on the protein produced by the S-carboxy-methyl groups. The heat and entropy of ionization of these groups in the reduced albumin are also "normal," in contrast to native albumin. Spectro-photometric titrations at 244 and 295 mmicro give equivalent results. The more open structure of the reduced albumin, as compared with the native protein, presumably allows the tyrosine groups to come freely into contact with solvent. In acid solutions the heights of the two peaks at 236 and 287 mmicro in the difference spectrum (albumin at pH 7 against albumin at a lower pH) are strictly proportional over the whole course of the titration. Both peaks apparently arise from changes in the environment of tyrosyl residues, rather than from more general conformational changes.

Humans↗
PubMed1968

Titration patterns of a murine sarcoma-leukemia virus complex: evidence for existence of competent sarcoma virions.

Stocks of inurine sarcoma virus show titration patterns ranging from one-to two-hit kinetics. The comparison of various titrations of this virus, both with and without added helper virus, to theoretical model systems composed of defined constituents, suggests the existence of a sarcoma virus that does not need coinfectinig murine leukemia virus to be manifested as a focus-forming unit. The behavior of such nondefective particles is compatible with a postulated leukemia-sarcoma virus hybrid.

Animals↗
PubMed2006

Titration and conditional knockdown of the prfB gene in Escherichia coli: effects on growth and overproduction of the recombinant mammalian selenoprotein thioredoxin reductase.

Release factor 2 (RF2), encoded by the prfB gene in Escherichia coli, catalyzes translational termination at UGA and UAA codons. Termination at UGA competes with selenocysteine (Sec) incorporation at Sec-dedicated UGA codons, and RF2 thereby counteracts expression of selenoproteins. prfB is an essential gene in E. coli and can therefore not be removed in order to increase yield of recombinant selenoproteins. We therefore constructed an E. coli strain with the endogenous chromosomal promoter of prfB replaced with the titratable P(BAD) promoter. Knockdown of prfB expression gave a bacteriostatic effect, while two- to sevenfold overexpression of RF2 resulted in a slightly lowered growth rate in late exponential phase. In a turbidostatic fermentor system the simultaneous impact of prfB knockdown on growth and recombinant selenoprotein expression was subsequently studied, using production of mammalian thioredoxin reductase as model system. This showed that lowering the levels of RF2 correlated directly with increasing Sec incorporation specificity, while also affecting total selenoprotein yield concomitant with a lower growth rate. This study thus demonstrates that expression of prfB can be titrated through targeted exchange of the native promoter with a P(BAD)-promoter and that knockdown of RF2 can result in almost full efficiency of Sec incorporation at the cost of lower total selenoprotein yield.

Amino Acid Sequence↗
PubMed1973

Acid-base titration of streptococci and the physical states of intracellular ions.

Acid titrations of intact and butanol-treated cells of Streptococcus faecalis revealed that nearly all of the intracellular K(+) ions could diffuse into the suspending medium in association with small anions, including ribonucleic acid breakdown products, when the cell membrane was damaged. In contrast, nearly all of the intracellular Mg(2+) ions appeared to be firmly bound to stable internal cell components but could be displaced reversibly by hydronium ions. The cell membrane acted as a barrier to ion movements, and Mg(2+) displacement from intact cells required more acid conditions, by as much as 2.5 pH units, than did displacement from butanol-damaged cells. Some 15 to 20% of the cell magnesium appeared to be associated with surface structures in that it could be removed at pH 7 with ethylenediaminetetraacetic acid or displaced by Co(2+), Ni(2+), Sr(2+), or La(3+). Magnesium could be displaced from isolated cell walls and membranes by hydronium ions in the pH range from 5 to 3, over which carboxyl groups were titrated. Displacement of magnesium from ribosomes also took place between pH 5 and 3, but it was more difficult to identify the magnesium-releasing groups because both protein carboxyl groups and purine and pyrimidine ring nitrogens can become protonated in this pH range. Isolated protoplast membranes remained structurally intact when completely depleted of magnesium. Furthermore, protoplasts isolated from intact cells were found to have greatly enhanced resistance to osmotic shock in acid media, even when solute loss was not extensive. Osmotic resistance was lost when the protoplasts were again placed in neutral media, and this reversibility suggested that acidification caused changes in the physical properties of membranes as well as solute leakage from cells.

Butanols↗
PubMed1966

Prophage repression as a model for the study of gene regulation. I. Titration of the lambda repressor.

Wiesmeyer, Herbert (Vanderbilt University, Nashville, Tenn.). Prophage repression as a model for the study of gene regulation. I. Titration of the lambda repressor. J. Bacteriol. 91:89-94. 1966.-The concentration of lambda repressor molecules within a lambda lysogenic cell was estimated from the multiplicity of superinfecting homologous phage necessary to permit replication and release of plaque-forming units. A multiplicity of 20 superinfecting phage was found sufficient to permit replication to occur in the normal lambda lysogen. The phage released after lysis of the superinfected lysogen was composed of both prophage and superinfecting phage types. Superinfection of the lysogen at lower multiplicities resulted in the lysis of only a small percentage of infected cells and is thought to represent a possible heterogeneity of repressor concentration in the lysogenic population. Viability of the superinfecting particle was found to be unnecessary for titration of the repressor. The repressor concentration in three lysogens of the nonultraviolet-inducible mutant of lambda, lambda(ind-), was found to be greater than 20 regardless of the host bacterium. However, the number of cells yielding phage after superinfection was found to vary with the particular host. The specificity of the lambda repressor was shown to be limited to homologous phage, as determined following heterologous superinfection experiments with phages T6r, 82c, 434c, 434hy, and 424. In all instances except that of superinfection with phage 434hy, only heterologous phage replication occurred. Superinfection by phage 434hy resulted in the release of both prophage and superinfecting phage types. The latter type represented approximately 80% of the total phage released.

Bacteriolysis↗
PubMed1976

Inherited resistance to N- and B-tropic murine leukemia viruses in vitro: titration patterns in strains SIM and SIM.R congenic at the Fv-1 locus.

We have investigated the titration patterns of murine leukemia viruses on mouse embryo cultures derived from a pair of congenic strains differing at the Fv-1 locus. XC plaque and infectious center assays carried out with N- and B-tropic viruses on both SIM (Fv-1nn) and SIM.R(Fv-1bb) host cells yielded results that were best approximated by Poisson one-hit curves. Titration curves of N-tropic virus by direct XC plaque assay were linear and parallel on the different hosts, with titers 1.8 to 2.7 log10 lower on SIM.R and on (SIM X SIM.R)F1 than on SIM cells; similar linear and parallel curves were found for B-tropic virus, with titers 1.4 to 2.0 log10 lower on SIM and (SIM XSIM-R)F1 than on SIM-R cells. In the infectious center assays, the proportion of infected cells was linearly related to multiplicity of infection on both permissive (N- on SIM and B- on SIM.R) restrictive (B- on SIM and N- on SIM.R) genotypes at multiplicities of infection below 0.5; the line relating the variables was about 1 log10 lower in the restrictive than in the permissive situations. At multiplicities of infection where the proportion of infected cells reached a plateau, differences between the results on permissive and restrictive genotypes were considerably reduced. This appeared to be due to the action of non-Fv-1 factors in permissive host. We conclude that the major action of the restrictive allele at the Fv-1 locus in this system is to reduce the probability of successful murine leukemia virus infection without a change in hitness.

Animals↗
PubMed1992

Overexpression of the influenza virus polymerase can titrate out inhibition by the murine Mx1 protein.

The murine Mx1 protein is an interferon-inducible protein which confers selective resistance to influenza virus infection both in vitro and in vivo. The precise mechanism by which the murine Mx1 specifically inhibits replication of influenza virus is not known. Previously, sensitive replication systems for influenza virus ribonucleoprotein, in which a synthetic influenza virus-like ribonucleoprotein is replicated and transcribed by influenza virus proteins provided in trans, have been developed. With these systems, the antiviral activity of the murine Mx1 protein was examined. It was found that continued expression of influenza polymerase polypeptides via vaccinia virus vectors can titrate out the inhibitory action of the murine Mx1 protein. This titration of inhibitory activity also occurs when the viral PB2 protein alone is overexpressed, suggesting that an antiviral target for the murine Mx1 polypeptide is the viral PB2 protein.

Animals↗
PubMed1993

Distinct properties of c-myc transcriptional elongation are revealed in Xenopus oocytes and mammalian cells and by template titration, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), and promoter mutagenesis.

A block to c-myc transcription elongation has been observed in Xenopus oocytes and mammalian cells. Here, we show that the distribution of RNA polymerase II transcription complexes in the c-myc promoter proximal region in Xenopus oocytes is different from that observed previously in mammalian cells. Thus, there are major differences in the c-myc elongation block observed in the two systems. In addition, as first reported for a Xenopus tubulin gene (K. M. Middleton and G. T. Morgan, Mol. Cell. Biol. 10:727-735, 1990). c-myc template titration experiments reveal the existence of two classes of RNA polymerase II transcription complexes in oocytes: one (at low template concentration) that is capable of reading through downstream sites of premature termination, and another (high template concentration) that does not. We show that these classes of polymerases are distinct from those previously identified by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), which distinguishes transcription complexes on the basis of transcribed distance, rather than on the basis of differential elongation through sites of premature termination. We also show that mutations that affect the efficiency of initiation of transcription from the c-myc P2 promoter can influence premature termination by at least two mechanisms: TATA box mutations function by the titration effect (decrease in transcription initiation results in a relative decrease in premature termination), while an upstream activator (E2F) site functions by contributing to the assembly of polymerase complexes competent to traverse the downstream sites of premature termination.

Animals↗
PubMed1985

Acid and gastrin responses during intragastric titration in normal subjects and duodenal ulcer patients with G-cell hyperfunction.

Amino acid induced acid and gastrin responses during intragastric titration at pH 2.5 and 5.5 were compared in normal subjects and duodenal ulcer patients with G-cell hyperfunction. The latter were identified on the basis of raised basal or maximal acid outputs and increased gastrin responses to feeding. In normal subjects the mixed amino acid meal stimulated only modest increases in serum gastrin, and the highest observed increase was about 30% that after a standard meal. In contrast, in the G-cell hyperfunction group the highest gastrin concentrations were similar to those after a standard meal. In the G-cell hyperfunction group the increment in serum gastrin at pH 2.5 expressed as a proportion of that at pH 5.5 was 0.29 indicating that the capacity of acid to inhibit gastrin release was well established in these patients. Acid secretory rates were close to maximal at both pH 2.5 and 5.5 during intragastric titration in the ulcer patients, but in normal subjects acid output was about 50% maximal at 2.5 and close to maximal at 5.5. The results suggest that the enhanced gastrin response to feeding in G-cell hyperfunction patients is because of increased sensitivity to amino acid stimulation rather than to diminished acid-inhibitory mechanisms.

Adult↗
PubMed2002

Longitudinal myocardial contraction improves early during titration with metoprolol CR/XL in patients with heart failure.

OBJECTIVE: To investigate diastolic and systolic left ventricular recovery during titration with metoprolol CR/XL (controlled release/extended release). DESIGN: Placebo run in, followed by an open study. SETTING: University hospital. PATIENTS: 14 patients with chronic heart failure. INTERVENTIONS: Metoprolol CR/XL titrated from 12.5 mg once daily to 200 mg once daily. MAIN OUTCOME MEASURES: M mode recordings of atrioventricular (AV) plane displacement, Doppler measurement of transmitral flow and pulmonary venous flow, two dimensional ejection fraction, and measurement of venous plasma concentration of noradrenaline. Patients were investigated after 2, 4, 6, and 24 weeks of treatment. RESULTS: A reduction of heart rate was observed on the first dose (12.5 mg once daily), from a mean (SD) of 74 (11) to 67 (11) beats/min, p < 0.05. This was accompanied by prominent effects on AV plane filling parameters, including an increase in early diastolic filling period from 87 (28) to 105 (33) ms (p < 0.05), and in the lateral AV plane fractional shortening from 8.7 (2.7)% to 10.2 (2.8)% (p < 0.05). An early trend towards improvement in global systolic left ventricular function was also seen, although this was not significant until six weeks. Ejection fraction increased from 33 (7.5)% to 38 (11)% (p < 0.05). CONCLUSIONS: First effects of left ventricular recovery during beta blocker treatment were seen in recordings of longitudinal performance, as expressed by AV plane displacement. Doppler flow dynamics as well as global systolic recovery appeared several weeks later, emphasising the importance of longitudinal performance in evaluating left ventricular function.

Adrenergic beta-Antagonists↗
PubMed1975

Carboxylesterases (EC 3.1.1). Purification and titration of chicken, sheep, and horse liver carboxylesterases.

Chicken, sheep, and horse liver carboxylesterases have been purified by procedures involving ammonium sulfate fractionation, ion-exchange chromatography and gel filtration on Sephadex. The actual yields of the procedures described were as follows: chicken, 1 g from 2 kg of liver powder (chloroform-acetone); sheep, 200 mg from 400 g of powder (chloroform-acetone); horse, 230 mg from 800 g of powder (acetone). The purified enzymes are free of non-carboxyl-esterase protein as shown by gel electrophoresis, although they do contain electrophoretic variants. The equivalent weight of the chicken enzyme is 67,000 based on titration with p-nitrophenyl diethyl phosphate or bis(p-nitrophenyl) phosphate, whereas those of the sheep and horse enzymes are similar to 69,500 and similar to 70,000, respectively, based on titration with p-nitrophenyl dimethylcarbamate.

Ammonium Sulfate↗