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PubMed1971

The influence of graded degrees of chronic hypercapnia on the acute carbon dioxide titration curve.

Studies were carried out to determine the influence of the chronic level of arterial carbon dioxide tension upon the buffering response to acute changes in arterial carbon dioxide tension. After chronic adaptation to six levels of arterial CO(2) tension, ranging between 35 and 110 mm Hg, unanesthetized dogs underwent acute whole body CO(2) titrations. In each instance a linear relationship was observed between the plasma hydrogen ion concentration and the arterial carbon dioxide tension. Because of this linear relationship, it has been convenient to compare the acute buffering responses among dogs in terms of the slope, dH(+)/dPaco(2). With increasing chronic hypercapnia there was a decrease in this slope, i.e. an improvement in buffer capacity, which is expressed by the equation dH(+)/dPaco(2)=-0.005 (Paco(2))(chronic) + 0.95. In effect, the ability to defend pH during acute titration virtually doubled as chronic Paco(2) increased from 35 to 110 mm Hg. The change in slope, dH(+)/dPaco(2), was the consequence of the following two factors: the rise in plasma bicarbonate concentration which occurs with chronic hypercapnia of increasing severity, and the greater change in bicarbonate concentration which occurred during the acute CO(2) titration in the animals with more severe chronic hypercapnia. These findings demonstrate the importance of the acid-base status before acute titration in determining the character of the carbon dioxide titration curve. They also suggest that a quantitative definition of the interplay between acute and chronic hypercapnia in man should assist in the rational analysis of acid-base disorders in chronic pulmonary insufficiency.

Acid-Base Equilibrium↗

PubMed1998

Dose-titration, multicenter study of oral transmucosal fentanyl citrate for the treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain.

PURPOSE: Supplemental, "as-needed," administration of an opioid is a common approach to the problem of breakthrough pain in cancer patients. Oral transmucosal fentanyl citrate (OTFC) is undergoing investigation as a new treatment for breakthrough pain. The primary purpose of the study was to demonstrate that a single-unit dose of OTFC can safely and effectively treat breakthrough pain. A secondary goal was to determine appropriate dosing guidelines. PATIENTS AND METHODS: This was a multicenter, randomized, double-blind, dose-titration study in 62 adult cancer patients using transdermal fentanyl for persistent pain. Consenting patients provided 2 days of baseline data to evaluate the performance of their usual breakthrough pain medication. Patients then randomly received 200 microg or 400 microg OTFC in double-blind fashion. (Patients were always assigned, rather than randomized, to 200 microg if 400 microg represented > 20% of around-the-clock medication.) Pain intensity (PI), pain relief (PR), and global satisfaction scores were recorded. OTFC was then titrated until the patient received adequate PR for each episode using one OTFC unit. Orders to titrate up were ignored one third of the time to improve the blind. Two days of baseline data were compared with 2 days of OTFC data after titration identified an effective dose of OTFC. RESULTS: Most patients (76%) found a safe and effective dose of OTFC. There was no meaningful relationship between the around-the-clock opioid regimen and the effective dose of OTFC. In open-label comparisons, OTFC produced a faster onset of relief and a greater degree of PR than patients' usual breakthrough medication. Somnolence, nausea, and dizziness were the most common side effects associated with OTFC. CONCLUSION: Most patients find a single OTFC dosage that adequately treats breakthrough pain. The optimal dose is found by titration and is not predicted by around-the-clock dose of opioids.

Administration, Buccal↗

PubMed1998

Optimizing growth hormone replacement therapy by dose titration in hypopituitary adults.

Although growth hormone (GH) replacement therapy is increasingly utilized in the management of adult hypopituitary patients, optimum dosing schedules are poorly defined. The use of weight-based or surface area-based dosing may result in overtreatment, and individual variation in susceptibility on the basis of gender and other factors is now being recognized. To optimize GH replacement and to explore further gender differences in susceptibility, we used a dose titration regimen, starting at the initiation of GH replacement therapy, in 50 consecutive adult-onset hypopituitary patients, and compared the results with those in 21 patients previously treated using a weight-based regimen. Titrated patients commenced GH 0.8 IU/day subcutaneously (0.4 IU/day if hypertensive or glucose tolerance impaired). Serum insulin-like growth factor I (IGF-I) was measured at 0, 2, 4, 6, 8, 10, and 12 weeks in all patients. Serum IGF binding protein 3 and acid labile subunit were measured at the same time points in 17 patients (8 male, 9 female). Patients were reviewed every 4 weeks and the dose of GH increased, if necessary, to achieve a serum IGF-I level between the median and the upper end of the age-related reference range. There was no significant difference between mean serum IGF-I at 2 and 4 weeks, or between 6 and 8 weeks, indicating that the full effects of a change in dose are evident within 2 weeks of that change. Maintenance doses were significantly higher in females than males [1.2 (0.8-2.0) vs. 0.8 (0.4-1.6) IU/day; median (range); P < 0.0001], and the median time to achieve maintenance dose was significantly shorter in males [4 (2-12) vs. 9 (2-26) weeks; P < 0.0001]. Median maintenance dose was lower overall than in a group of 21 patients initially commenced on GH using a weight-based dosing schedule, with subsequent adjustment of dose during clinical follow-up [1.5 (0.4-3.2) IU/day; P = 0.02]. Reduction in waist measurement and waist to hip ratio at 6 and 12 months was similar in females (P < 0.001) and males (P < 0.01). Well-being improved significantly after 3 months of GH therapy (14.2 +/- 5.9 vs. 7.4 +/- 4.5 SD; P < 0.0001), and there were no gender differences. Adult Growth Hormone Deficiency Assessment (AGHDA) scores at 6 months were similar to maintenance scores in patients commenced on weight-based regimens. Measurements of ALS and IGFBP-3 added no useful extra information to IGF-I in managing the dose titration. The practical scheme outlined for dose titration of GH replacement resulted in rapid achievement of lower maintenance doses than those achieved using conventional weight-based regimens without loss of efficacy. It was particularly important in female patients who demonstrated decreased overall sensitivity to GH and required higher doses to achieve the same effects as males. This constitutes the first report of a uniform titration regimen based on a defined target range of serum IGF-I in a large patient cohort.

Adolescent↗

PubMed1999

Titration by estrogen receptor activation function-2 of targets that are downstream from coactivators.

Cross-interference (squelching) among nuclear receptors has been proposed to reflect the titration of coactivators that bind the receptors in a hormone-dependent manner. We have tested whether the coactivators are the only target titrated during squelching of one receptor by another, or whether proteins needed for coactivator function are titrated as well. That the coactivators are indeed one target of squelching is apparent. The isolated ligand-binding domain of the estrogen receptor (ER-LBD) squelches transcriptional activation by the thyroid hormone receptor (TR) only when the LBD is bound to ligands that promote coactivator interactions and only when regions of the LBD that promote coactivator interactions are undisturbed. Furthermore, the ER-LBD and the TR compete in vitro for the related p160 coactivators, SRC1a and GRIP1 (glucocorticoid receptor interacting protein 1), or the putative corepressor, RIP140. Finally TR action becomes more potent when coactivator levels are raised. Nonetheless, supplying excess SRC1a or GRIP1 does not abolish squelching by the ER. In fact, squelching becomes even more severe when coactivators are abundant. Supplying combinations of coactivators from the p160 class and the CREB-binding protein (CBP)/p300 class makes squelching most severe. Elevated RIP140 inhibits TR action, but also protects the residual TR action from squelching by the ER-LBD. We conclude that ER-LBD squelches TR both by titrating p160-CBP coactivators and additionally by cooperating with the coactivators to titrate a second factor. The second factor would be needed by the TR for coactivator-mediated transcriptional stimulation.

Adaptor Proteins, Signal Transducing↗

PubMed2003

A disposable voltammetric cell for determining the titratable acidity in vinegar.

A disposable voltammetric cell using three pencil leads as working, reference, and counter electrodes was developed for determining the titratable acidity, i.e. the acid content in vinegar. The materials of the pencil leads were graphite-reinforcement carbons (GRCs). A voltammetric determination of acid was made by measuring the reduction prepeak current of 3,5-di-t-butyl-1,2-benzoquinone (DBBQ) due to the presence of acids in unbuffered solution. The potential stability of the pseudo-reference electrode of GRC was examined. The prepeak current was found to be proportional to the acetic acid concentration from 0.05 to 2.7 mM with a correlation coefficient of 0.999. The cell-to-cell reproducibility for 1 mM acetic acid was evaluated with ten individual disposable cells. The RSD of the prepeak current and the SD of the prepeak potential were 2.56% and 0.008, respectively. The titratable acidity in five vinegar samples was determined by voltammetry using disposable cells and compared with that of the titratable acidity determined by the conventional potentiometric titration method. We then observed the results by both methods, and found a correlation coefficient of 0.972. As such, the voltammetry using disposable-cell required only one thousandth the volume of a vinegar sample for the titration method. The disposable cell was superior to the conventional electrochemical cell, in terms of facility, environment-friendly, and economy, and thus a sensor using the present cell would be useful for routine work in the quality control of vinegar.

Acetic Acid↗

PubMed2004

[A trial of titration in oral appliance therapy for obstructive sleep apnea syndrome].

This study evaluated the effect of titration in oral appliance therapy for obstructive sleep apnea syndrome (OSAS), and examined problems with this test. However, the method of predicting the appropriate mandible position has not yet been established. In this study, titration was attempted in order to predict appropriate mandible position prior to wearing an oral appliance. Twenty-three male patients diagnosed as OSAS by a physician participated in this study. The mandible was protruded by a titratable splint (TS) until apneic and hypopneic signs had disappeared. Moreover, polisomnography (PSG) was used to monitor brain wave patterns, eye movement, muscle tone, body movement and breathing. Sleep study was performed by a portable sleep monitoring device before and after examination wearing titrated oral appliance (OA), and the effect of therapy was evaluated. The results obtained were as follows. 1. In the Apnea Hypopnea Index (AHI), Apnea Hypopnea density (AH density), lowest SpO2, Oxygen Desaturation Index (ODI), there was a statistically significant improvement. The mean AHI reduced from 13.8 to 4.7 (p<0.001). The mean AH density reduced from 12.0 to 3.5 (p<0.001). The mean lowest SpO2 increased from 78.7 to 84.7 (p<0.0001). The mean ODI reduced from 15.7 to 6.1 (p<0.001). 2.. The average proportion of protrusive distance for movable distance was 71.7%. 3. Only one patient complained of discomfort in the maxillofacial region, however, this discomfort disappeared after adjustment of OA. Therefore, it is suggested that titration for OA is a very useful examination for OSAS therapy.

Adult↗

PubMed1999

[Auto-CPAP in the titration and treatment of obstructive respiratory sleep disorders].

Self-adjusted Continuous Positive Airway Pressure or autoCPAP machines have been engineered to automatically adjust the pressure to maintain the upper airway patency. They can be used for titration or long-term home therapy. They have been developed to improve efficiency and compliance of CPAP treatment and the cost-effectiveness of titration and also to decrease the long waiting lists for manual titration. For the treatment, it is believed, but not demonstrated, that compliance may be increased by lowering the optimal pressure. Most machines are piloted by an algorithm based on detection of various combination of respiratory events such as apnoeas, hypopnoeas, snoring, inspiratory flow limitation or impedance. Several short-term studies have shown that autoCPAP reduces the indices of respiratory events and microarousals. In general, optimal CPAP determined automatically are identical or lower than evaluated manually by experienced technicians. However, the long-term benefits of auto-CPAP on compliance have not been determined and require further controlled clinical studies taking account not only compliance, but also sleep quality, quality of life, alertness and cognition for each autoCPAP. The cost-effectiveness of auto-titration versus conventional titration remains also to be established.

Algorithms↗

PubMed2000

[Auto-controlled continuous positive pressure in the titration and treatment of obstruction sleep disorders].

Airway Resistance↗

PubMed2000

[Comparison of automatic (AUTO-CPAP)and "manual" CPAP pressure titration in patients with obstructive sleep apnea].

UNLABELLED: Auto-CPAP gives an opportunity to decrease costs of evaluating patient with OSA, replacing manual titration of pressure during PSG. The aim of this study was to compare automatic (auto-CPAP) and manual CPAP pressure titration in patients with OSA. We studied 50 obese patients (BMI--35 +/- 6 kg/m2), mean age 52.4 +/- 9.4 years with severe OSA, mean: AHI--62.9 +/- 22.1, mean overnight SaO2--89.1 +/- 3.7%, T90--54.4 +/- 29.6%. Two polysomnographies were performed: first when patient slept with CPAP and pressure was titrated manually by a technician and second on auto-CPAP device. Both methods had similar efficacy in reduction of AHI (< 10/h) and hypoxaemia, despite lower pressure established during auto-CPAP mode preventing apnoeas and hypopnoes during 90% of sleep time (8.2 +/- 1.7 cm H2O) compared to manual CPAP titration (9.2 +/- 1.7 cm H2O) (p < 0.05). CONCLUSION: Auto-CPAP seems to be a reliable alternative to manual titration of the therapeutic pressure in patients with OSA. This may help to cut a waiting list for PSG of patients suspected of OSA.

Adult↗

PubMed1990

The titration of death: a new sin.

..."Titration of death" is the phrase I have used, in private musings and discussions, to express the undertaking of causing or permitting death to occur within carefully delimited parameters. It is, I think, a new form of sin. I distinguish it from a similar enterprise, in principle benign, that we might call "titration of dying," which attempts to manage the dying process. The focus of attention of titration of dying is the experience of the patient prior to death, with little or no concern given to the condition of the cadaver following death. Titration of death, on the other hand, is primarily concerned with producing, at the close of the process, a cadaver that is usable in some manner; and titration of death, per se, has only incidental concern with the dying process.

Aborted Fetus↗

PubMed2002

On-line titration of non-ionic surfactants in wastewater treatment plants using a specific electrode.

Textile finishing industry wastewater often contains high concentrations of surfactants. Non-ionic surfactants like alcohol ethoxylates are among the most used surfactants and are discharged from batch-processes in widely varying concentrations. The anaerobic biomass and especially methanogenic microorganisms have been shown to be inhibited by surfactants. To protect these microorganisms from irreversible inhibition a measurement of the surfactant concentration is useful for the process control, but most analytical methods are too complicated and expensive for an on-line process control. It was shown that the titration of non-ionic surfactants is possible in the presence of biomass and in wastewater from textile wet processes using the Metrohm NIO-electrode. Titration and sampling were successfully performed with standard equipment. The software used for the process control of a lab-scale anaerobic treatment plant was also used to evaluate the obtained titration curves. This allowed performing the titrations without using a more expensive titrator.

Alcohols↗

PubMedDate not supplied

Application of rapid, electrochemical Flash Titration to total acidity and alkalinity determinations in buffers, foods, and beverages.

A new technique (Flash Titration) for the determination of total acidity and total alkalinity was applied to food and beverage analysis. Requiring no liquid titrants, Flash Titration is a technique made possible through microfabrication of electrochemical components on a silicon chip. Acidic or basic titrant was generated electrochemically at a noble-metal electrode that intimately surrounded an ion-selective, field-effect transistor pH sensor. As acid or base was generated through electrolysis, sample alkalinity or acidity, respectively, was neutralized in the immediate vicinity of the electrode. Through diffusion, a zone comprising a gradient of partially to totally neutralized sample expanded from the generating electrode into the volume element sensed by the nearby pH sensor. An analysis of the pH signal versus time revealed an end point inflection at an elapsed time related to the total alkalinity or acidity of the sample. End point times were typically a few seconds. In this paper, Flash Titration was applied to the analysis of a variety of samples, including juices, soft drinks, wines, and food products. The differences between the results obtained by the Flash Titration method and a commonly used conventional volumetric method were less than 2% in most food products tested. Analysis costs were reduced both through time saving and reduction or elimination of hazardous liquid titrant disposal, by the use of the Flash Titration method.

Beverages↗

PubMed1991

31P nuclear magnetic resonance and zero-point titration compared for measuring free magnesium concentration in erythrocytes.

Intracellular ionized magnesium concentrations ([Mg2+]i) were measured in erythrocytes by 31P nuclear magnetic resonance (NMR) and zero-point titration in 14 controls and seven patients with renal magnesium loss. The mean intracellular ionized magnesium concentration in controls measured by 31P NMR was 0.20 (SD 0.03) mmol/L cell water, compared with 0.55 (SD 0.12) mmol/L cell water by zero-point titration. Total erythrocyte magnesium content measured with the lysate method was 0.63 mmol/L cell water higher than estimated by 31P NMR, probably because not all magnesium complexes are fully visible to the NMR technique. We found a positive correlation between plasma ultrafiltrable magnesium and [Mg2+]i irrespective of the [Mg2+]i assay used. [Mg2+]i measured with 31P NMR correlated modestly but significantly with [Mg2+]i determined by zero-point titration (r = 0.58, P less than 0.02). Washing erythrocytes before the zero-point titration decreased the ATP content and the cell water fraction, which led to overestimation of [Mg2+]i by zero-point titration. Although absolute values for [Mg2+]i differ with the assay used, both methods determined significantly lower values for [Mg2+]i in patients with isolated renal magnesium loss.

Adenosine Triphosphate↗

PubMed1984

Determination of surface charge of some bacteria by colloid titration.

The surface charge of bacteria is always negative except below pH 2. The negative charge depends mainly upon phosphate and carboxyl groups. The charge of six kinds of bacteria was determined by colloid titration between pH 2 and 11. When there is amino group on the cell surface, it is positive as ammonium cation between pH 2 and 10, and it combines with the negative groups to neutralize the negative charge. In the presence of formalin, the colloid titration results show that the free amine is blocked by formalin, and the amino group can be estimated by the difference between the two titration results. Above pH 10, the titration results of Escherichia coli and Salmonella typhi in the presence of formalin implied the existence of guanidyl group. The titration results of living bacterial suspensions were quite the same as those of heat-killed ones.

Amines↗

PubMed1994

Speed and duration of dose titration with the angiotensin converting enzyme inhibitor quinapril: relationship with efficacy in patients with moderate hypertension.

Most antihypertensive agents, including ACE inhibitors, are routinely dose titrated upwards every two weeks in both clinical trials and clinical practice to achieve control of systemic pressure. Two separate clinical trials assessing comparative antihypertensive efficacy of quinapril versus other ACE inhibitors (enalapril and captopril) were conducted in a double-blind fashion in patients with moderate to severe hypertension already receiving a diuretic (study I: entry DBP > or = 105 and < or = 120 mmHg while taking 25 mg hydrochlorothiazide; study II: DBP > or = 110 and < or = 130 mmHg while taking 25 mg chlorthalidone). In study I, 88 patients were randomised to receive quinapril (10-40 mg twice daily) which was titrated upwards every one to two weeks as necessary to reduce DBP < or = 90 mmHg (titration period six weeks, followed by an additional six weeks of therapy during which open-labelled beta-blocker therapy could be added for nonresponders). In study II, 84 patients were randomised to receive quinapril (5-20 mg twice daily) which was titrated upwards every four weeks as necessary to reduce DBP < or = 90 mmHg (titration period 16 weeks, followed by a 12-week maintenance period). Both cohorts of patients were demographically slightly dissimilar because there were more females and higher baseline DBP in study II versus study I (60% vs 34%, and 115.0 vs 109.1 mmHg, respectively) and more blacks (26% vs. 0%) and heavier patients (90 kg vs. 73 kg) in study I versus study II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Quantitation of DNA topoisomerase II alpha messenger ribonucleic acid levels in a small cell lung cancer cell line and two drug resistant sublines using a polymerase chain reaction-aided transcript titration assay.

BACKGROUND: We have modified a polymerase chain reaction (PCR)-aided transcript titration assay (1) in order to allow quantitation of low amounts of DNA topoisomerase II alpha mRNA in small RNA samples. EXPERIMENTAL DESIGN: The titration assay was used to quantitate the amount of DNA topoisomerase II alpha mRNA in a human small cell lung carcinoma cell line, GLC4 and its drug-resistant sublines, GLC4/ADR and GLC4/CDDP. These cell lines show differences in DNA topoisomerase II alpha protein level and DNA topoisomerase II enzyme activity. To validate the titration assay, the results were compared with the results of a DNA topoisomerase II enzyme activity assay and DNA topoisomerase II alpha northern and western blotting assays. RESULTS: Using the titration assay, we were able to quantitate DNA topoisomerase II alpha mRNA on a picogram level starting with less than 1 micrograms of total RNA/cell line. GLC4/ADR showed a markedly decreased DNA topoisomerase II alpha mRNA level that seemed to be unchanged in GLC4/CDDP when compared with the parental cell line. The results obtained with this assay are confirmed by the western blot data and are not in contradiction with the northern blot results obtained for the three cell lines. CONCLUSIONS: The DNA topoisomerase II alpha titration assay is a highly sensitive new technique to study the role of DNA topoisomerase II alpha in drug resistance and may help to identify cancer types and patients most likely to respond to DNA topoisomerase II targeted drugs. The decrease in DNA topoisomerase II alpha protein level and DNA topoisomerase II activity in GLC4/ADR may result from transcriptional down regulation of DNA topoisomerase II alpha.

Antigens, Neoplasm↗

PubMed1994

Electrocardiographic and cardiovascular effects of subconvulsive stimulation during titrated right unilateral ECT.

The American Psychiatric Association Task Force on ECT has recommended that electroconvulsive therapy (ECT) stimuli be dosed at "moderately suprathreshold" intensities. Empiric estimation of the convulsive threshold by stimulus dose titration may expose the patient to subconvulsive stimuli, and subconvulsive stimuli have been reported by some to carry serious cardiovascular risk. This study examines the electrocardiographic (ECG) and cardiovascular effects of subconvulsive stimuli. Forty consecutive inpatients (29 women, 11 men; mean age 68 years) with major depression received subconvulsive stimuli during titrated, right unilateral (RUL) ECT. Successively larger stimuli were administered until a convulsion began. The effects of subconvulsive stimuli on the ECG, heart rate (HR), and blood pressure (BP) were assessed with multivariate repeated measures analysis. Subconvulsive stimuli prolonged the R-R interval and decreased HR compared with baseline values immediately before the subconvulsive stimulus, but the changes were of questionable clinical significance. BP was not changed. In conclusion, subconvulsive stimuli are well tolerated in the context of titrated RUL ECT. If stimulus dose titration proves to be useful in optimizing efficacy with fewer cognitive side effects, then cardiovascular considerations should not be an obstacle in the application of stimulus dose titration in most patients.

Aged↗

PubMed1976

Titration behavior of individual tyrosine residues of myoglobins from sperm whale, horse, and red kangaroo.

The titration behavior of individual tyrosine residues of myoglobins has been studied by observing the pH dependence of the chemical shifts of Czeta and Cgamma of these residues in natural abundance of 13C Fourier transform NMR spectra (at 15.18 MHz, in 20-mm sample tubes, at 37 degrees) of cyanoferrimyoglobins from sperm whale, horse, and red kangaroo. A comparison of the pH dependence of the spectra of the three proteins yielded specific assignments for the resonance of Tyr-151 (sperm whale) and Tyr-103 (sperm whale and horse). Selective proton decoupling yielded specific assignments for Czeta of Tyr-146 of the cyanoferrimyoglobins from horse and kangaroo, but not the corresponding assignment for sperm whale. The pH dependence of the chemical shifts indicated that only Tyr-151 and Tyr-103 are titratable tyrosine residues. Even at pH 12, Tyr-146 did not begin to titrate. The titration behavior of C zeta and Cgamma of Tyr-151 of sperm whale cyanoferrimyoglobin yielded a single pK value of 10.6. The pH dependence of the chemical shift of each of the resonances of Tyr-103 of the cyanoferrimyoglobins from horse and sperm whale could not be fitted with the use of a single pK value, but was consistent with two pK values (about 9.8 and 11.6). Furthermore, the resonances of Czeta and Cgamma of Tyr-103 broadened at high pH. The titration behavior of the tyrosines of sperm whale carbon monoxide myoglobin and horse ferrimyoglobin was also examined. A comparison of all the experimental results indicated that Tyr-151 is exposed to solvent, Tyr-146 is not exposed, and Tyr-103 exhibits intermediate behavior. These results for myoglobins in solution are consistent with expectations based on the crystal structure.

Animals↗