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PubMed2006

Seizure threshold determination for electroconvulsive therapy: stimulus dose titration versus age-based estimations.

OBJECTIVE: This study compared electroconvulsive therapy (ECT) seizure threshold determined by stimulus dose titration with age-based estimations. METHOD: Patients with major depressive disorder had their initial seizure thresholds determined by stimulus dose titration and the results compared with age-based estimations. There are no significant differences in thresholds determined by these methods. RESULTS: Two hundred and three psychiatric patients (149 females, 54 males) had their seizure thresholds determined by stimulus dose titration. There was a significant positive correlation between seizure thresholds and age for males and females with male thresholds greater than female thresholds. Age determinations of seizure threshold would have resulted in excessive initial treatment stimuli for 30% of females and 8% of males. Ineffective stimulus doses would have been given to 2% of females and 7% of males on a full age basis and 64% using a half age strategy. CONCLUSIONS: For effective high-dose right unilateral ECT, initial seizure threshold should be determined by stimulus dose titration.

Adolescent↗
PubMed2005

Intravenous versus subcutaneous morphine titration in patients with persisting exacerbation of cancer pain.

BACKGROUND: Patients with cancer pain with initially adequate analgesia under oral sustained-release opioid medication may suffer from persisting pain exacerbations. Sometimes even fast help is needed and then optimally performed by intravenous application (IVA) of immediate-release (IR) opioids. This IVA, however, may only be performed by physicians in Germany. OBJECTIVE: We wanted to find out if subcutaneous application of IR-opioids might be an adequate alternative to IVA in persisting pain exacerbations of patients with cancer pain because this could be performed by the nursing staff in Germany as well. DESIGN: An open randomized controlled trial was used to compare intravenous versus subcutaneous morphine titration in persisting pain exacerbations in patients with cancer pain. SETTING/SUBJECTS: Thirty-nine patients with cancer (21 intravenously, 18 subcutaneously) of the pain management department of the university hospital of Cologne, Germany were included into the study. MEASUREMENTS: Calculated from preexisting analgesic medication boli of morphine were given every 5 minutes (intravenously) or 30 minutes (subcutaneously) up to adequate analgesia or intolerable side effects. Pain intensity, nausea, sedation, and some vital parameters were documented before the start, after each application and at the end of titration. RESULTS: Thirty-five patients were pretreated with oral opioids, 4 patients with nonopioid analgesics. Six patients stopped titration because of intolerable side effects (sedation, vomiting). Thirty patients (77%) reported at least sufficient pain reduction, 3 patients were free of pain (intravenously). Mean pain intensity decreased on a visual analogue scale (VAS, 0-100) from 83 to 32 (intravenously) and from 68 to 42 (subcutaneously). Morphine doses ranged from 4 mg to 32 mg (intravenously; mean, 18.5 +/- 9.2 mg) and from 10 mg to 200 mg (subcutaneously mean, 57.9 +/- 59.6 mg). Mean time up to adequate analgesia was 53 (intravenously) 77 min (subcutaneously), respectively. There was no change in vital parameters but an increase of sedation in both groups. The adaptation of the continuous analgesic medication resulted in a stable and lasting pain relief after 4 days in both groups. CONCLUSIONS: Intravenous and subcutaneous-morphine titration are adequate to antagonize persisting pain exacerbations in cancer pain patients quickly and to adapt the continuous opioid analgesic medication.

Adult↗
PubMed2001

Sevoflurane titration using bispectral index decreases postoperative vomiting in phase II recovery after ambulatory surgery.

UNLABELLED: We tested the hypothesis that titration of sevoflurane using bispectral index (BIS) of the electroencephalogram decreases postoperative nausea and vomiting and improves recovery after outpatient gynecologic laparoscopy. After propofol induction, anesthesia was maintained in all patients with sevoflurane in 65% nitrous oxide and oxygen. In the BIS-Titrated group (n = 32), sevoflurane was titrated to maintain the BIS between 50 and 60 during surgery. In the Control group (n = 30), sevoflurane was adjusted to keep hemodynamic variables within 25% of control values. The severity of pain, postoperative nausea and vomiting, and recovery variables were recorded. In the Control group, 30% of the patients had BIS <40 during surgery (versus 0 in the BIS-Titrated group). Orientation and ability to drink were achieved earlier in the BIS group (P < 0.05). At 30 min after cessation of nitrous oxide, patients in the BIS group performed better in the psychomotor recovery test (P < 0.01). In Phase II recovery room, these patients had significantly less vomiting than the patients in the Control group (16% versus 40% of the patients, respectively, P < 0.05). No differences were found in times to achieve home readiness. IMPLICATIONS: In patients undergoing outpatient gynecologic laparoscopy, the monitoring of bispectral index decreases vomiting in Phase II recovery room, but it has no effect on the time to achieve home readiness.

Adult↗
PubMed2002

Ethnic differences in titratable acid excretion and bone mineralization.

PURPOSE: To test our hypothesis that differences in urinary calcium excretion among blacks and whites may be secondary to ethnic variations in acid (H(+)) metabolism and to prove that increases in titratable acid excretion would be found among individuals predisposed to the development of stress fractures. METHODS: We administered 8 g NH(4)Cl acutely to 11 black and 18 white healthy volunteers and measured urinary sodium, calcium, and acid excretions. We measured the Na(+)/H(+) antiporter activity using acid-loaded platelets as surrogate markers for this exchanger expressed in renal epithelial cells. We also compared differences in titratable acid excretion among a cohort of subjects with, and without, a history of stress fracture. RESULTS: NH(4)Cl-induced increases in titratable urinary acid correlated with changes in the renal excretion of calcium and sodium, and stimulated acid excretion correlated with basal acid loss. Despite comparable changes in plasma pH, whites, when compared to blacks, had much greater basal acid excretion and NH(4)Cl-induced acid excretion. Whites also had much greater baseline calcium excretion rates when compared to blacks. Following acid loading, whites continued to exhibit greater calcium excretion rates than blacks. Acid loading significantly decreased sodium excretion in whites but not in blacks. Blacks also had significantly attenuated Na(+)/H(+) exchange activity. In a cohort of resting, athletic students, we found enhanced basal H(+) and phosphate excretion among subjects who experienced stress fractures during their rigorous physical training when compared to those individuals who did not. CONCLUSION: Blacks may have a greater endogenous buffering capacity than whites, or the reported ethnic differences in sodium and calcium excretion rates between blacks and whites may be secondary to racial variations in renal H(+) excretion. We conclude that both ethnic differences in bone mineralization and bone integrity in athletes are mediated by heritable differences in titratable acid excretion.

Acid-Base Equilibrium↗
PubMed1998

Feasibility of the titration method of mild hypothermia in severely head-injured patients with intracranial hypertension.

OBJECTIVE: Clinical strategy to maximize effectiveness and to minimize adverse influences remains to be determined for mild hypothermia therapy for traumatic brain injury. This study was conducted to evaluate the clinical feasibility of the titration method of mild hypothermia in severely head-injured patients in whom a reduction in intracranial pressure was regarded as the target effect. METHODS: Nine consecutive patients with severe head injury were studied. Patient age ranged between 18 and 66 years, Glasgow Coma Scale scores were equal to or less than 8, and intracranial pressures were equal to or greater than 20 mm Hg despite removal of intracranial hematoma and drugs, including glycerol and thiopental. During a maximum of 6 days of hypothermia therapy, jugular venous blood or cerebrospinal fluid temperature was titrated to reduce intracranial pressure to less than 20 mm Hg by means of repeated intragastric cooling with our nasoduodenal tube and surface cooling. The feasibility and the effects on systemic complications of this titration method of mild hypothermia were evaluated. RESULTS: Intracranial pressure variably decreased from before to 3 hours after the beginning of all procedures of cooling. The mean intracranial pressure significantly decreased from 24 to 15 mm Hg with cooling, while temperature reduced an average of 2.0 degrees C. Four patients had systemic infection complications. Increased C-reactive protein and decreased platelet count were observed in all patients during hypothermia. The incidence of good recovery and moderate disability according to the Glasgow Outcome Scale was seven of nine patients. CONCLUSION: The titration method of mild hypothermia to control intracranial hypertension in severely head-injured patients is clinically feasible. However, the method failed to reduce the incidence of infectious and hematological complications.

Adolescent↗
PubMed2003

Effects of titrated arginine vasopressin on hemodynamic variables and oxygen transport in healthy and endotoxemic sheep.

OBJECTIVE: To determine the effects of titrated arginine vasopressin (AVP) alone or in combination with norepinephrine (NE) on hemodynamics and oxygen transport in healthy and endotoxemic sheep. DESIGN: Prospective controlled trial. SETTING: University research laboratory. SUBJECTS: Six adult ewes. INTERVENTIONS: Healthy sheep received AVP as a titrated infusion, initiated with 0.6 units/hr and increased by 0.6 units/hr every 15 mins, either until mean arterial pressure was increased by 20 mm Hg vs. baseline or a maximum of 3.6 units/hr was administered. After 90 mins, AVP infusion was continued with the investigated dosage, and NE (0.2 microg x kg(-1) x min(-1)) was also infused for 90 mins. After a 24-hr period of recovery, endotoxemia was induced and maintained (Salmonella typhosa endotoxin, 10 ng x kg(-1) x min(-1)) in the same sheep for the next 19 hrs. After 16 hrs of endotoxemia, AVP and NE were administered as described previously. MEASUREMENTS AND MAIN RESULTS: Hemodynamics were obtained at baseline, every 15 mins during the titration period, and 60 and 90 mins after additional NE infusion. Variables of oxygen transport were calculated before and after the titration period. In healthy and endotoxemic sheep, AVP reduced heart rate and cardiac index (p <.001) and compromised oxygen delivery (p <.001) and oxygen consumption (healthy sheep, p =.003; endotoxemic sheep, p <.001). Vasopressin infusion did not alter mean pulmonary arterial pressure but increased pulmonary vascular resistance index in both groups (p <.001). Additional infusion of NE further augmented mean arterial pressure and increased cardiac index during endotoxemia (p <.001). This was accompanied by an increase in oxygen delivery and consumption (p <.05 each). CONCLUSIONS: During ovine endotoxemia, AVP decreased cardiac index, compromised oxygen delivery, and increased pulmonary vascular resistance index. These side effects may limit its use as a sole vasopressor during sepsis. Potentially, a simultaneous infusion of AVP and NE could represent a useful therapeutic option.

Animals↗
PubMed1983

Altered scrapie infectivity estimates by titration and incubation period in the presence of detergents.

During experiments on the purification of scrapie infectivity, changes were found in the dynamics of scrapie titration. After exposure to detergent, infectivity estimates by both endpoint titration and incubation period were altered. The addition of detergent to the diluent used in titration resulted in at least a 100-fold increase in the infectivity estimate. This suggests that the amount of scrapie in a sample, as measured by serial dilution and titration, may be underestimated to different extents, depending on the biochemical milieu of the inoculum. Membrane fractions treated with detergents before dilution exhibited longer incubation periods than untreated fractions for the same number of infectious units of scrapie. This demonstrates that detergent treatments and possibly other biochemical manipulations can cause changes in the response of the host to the inoculum that are not detectable if incubation periods alone are used to estimate scrapie 'titre'.

Animals↗
PubMed1979

Titration of Isolated Cell Walls of Lemna minor L.

A theoretical model has been built to bypass the equation of titration of the cell wall. This equation, which is an extension of the Henderson-Hasselbach equation, underlines the importance of the exchange constant, the ionic strength as well as the rate of neutralization. The model is restricted to the case when the ionization degree is equal to the neutralization degree. The shape of the titration curve is shown to be strongly dependent on the valency of the base used.Experimental results have shown that isolated cell walls bear at least two kinds of sites. The first sites which are titrated after a short time of equilibration are attributed to polyuronic acids (capacity: 0.3 milliequivalents per gram fresh cell walls). The second sites, are obtained after a long time of equilibration (capacity: 1.2 to 1.3 milliequivalents per gram, fresh cell walls). Titrations have been performed with different bases [KOH, NaOH, and Ca(OH)(2)] and under different ionic strengths.The results obtained with NaOH and KOH do not exhibit any difference of selectivity. Conversely, the sites have a much bigger affinity for the Ca(2+) ions than for the monovalent ones. The apparent pKa of the uronic acids was estimated to lie between 3.0 and 3.4; this is consistent with the values obtained with polyuronic acid solutions.

Journal Article↗
PubMedDate not supplied

BNP-guided therapy not better than expert's clinical assessment for beta-blocker titration in patients with heart failure.

B-type natriuretic peptide (BNP) is a cardiac neurohormone used as a noninvasive tool for diagnosing and monitoring heart failure. Beta blockers have beneficial effects in patients with heart failure as well as a direct effect on BNP plasma levels. The aim of this study is to compare the efficacy of a BNP-guided approach vs. standard care on beta-blocker titration in heart failure patients. Forty-one patients with heart failure were randomized into a clinical trial. Bisoprolol was started, and the dose was regularly up-titrated. BNP was measured monthly. The clinical group had beta-blocker dosage increased according to standard care, whereas the BNP group had beta-blocker dosage up-titrated according to plasma BNP levels plus standard care. The primary outcome was mean beta-blocker dose achieved after 3 months. BNP levels, left ventricular ejection fraction, clinical score, quality of life, and hospitalization were collected in all patients. BNP-guided up-titration of beta blocker in ambulatory patients with heart failure did not result in higher doses of beta blocker at the end of 3 months+/-SD (5.9+/-4.3 mg vs. 4.4+/-3.4 mg, p=0.22). Left ventricular ejection fraction was significantly improved in both groups by 7.3% (95% confidence interval, 4.1%-10.4%; p<0.0001). A trend toward better quality of life was seen in the BNP group.

Adrenergic beta-Antagonists↗
PubMed1985

Use of chicken cell line LSCC-H32 for titration of animal viruses and exogenous chicken interferon.

The chicken embryo cell line LSCC-H32 was tested for the propagation and titration of several animal viruses of the families Toga-, Reo-, Rhabdo-, Herpeto-, Orthomyxo-, Paramyxo-, and Poxviridae and compared with secondary chicken embryo cells. The LSCC-H32 cells were demonstrated to be as susceptible for most of the tested viruses as were secondary chicken embryo cells. Both produced comparably sized virus plaques. The titers of Sindbis and Semliki Forest viruses in LSCC-H32 cells were 5- to 40-fold higher than in secondary chicken embryo cells or BHK-21 cells, respectively. Furthermore, exogenous chicken standard interferon was titrated in the LSCC-H32 cells, and a 50% plaque titer reduction of the challenging vesicular stomatitis virus was achieved by 0.12 IU of a standard chicken interferon preparation. Endogenous chicken interferon could not be induced by treatment of the cells with polyinosinic acid-polycytidylic acid. Due to its high plating efficiency and metabolic activities, the LSCC-H32 cell line provides a useful cell system for the titration and large-scale production of the tested animal viruses and for the titration of exogenous chicken interferon.

Animals↗
PubMed1978

Microbiological titration of proteins and of single amino acid content in biological materials without purification and hydrolysis.

A method is described for the microbiological determination of the protein content of biological materials. This method can also be adopted to titrate the concentration of a single amino acid in the protein and has the following advantages: (1) titration can be done without purification and hydrolysis of proteins; (2) the titration graph is a straight line between 25 and 800 microgram/ml; (3) protein values agree with those obtained using the Kjeldhal method; and (4) each mutant requiring one amino acid may be used to titrate the concentration of a single amino acid of the protein. The leucine content of various kinds of flour was measured with this system.

Amino Acids↗
PubMed1994

Correct titration of non-drugs and some other methodological issues.

Doctors' prescription and dosing behaviour was investigated using data from 9 clinical trials in 550 patients treated with psychotropics. 7 trials were conducted under double- and 2 under single-blind conditions. In 3 of these trials, oral and i.m. preparations were used demanding a double-dummy design. All patients were evaluated on a weekly or 2-week basis using psychopathological rating scales (i.e. Hamilton Anxiety Scale, Hamilton Depression Scale, Clinical Global Impressions, Simpson and Angus EPS). It was found that (a) oral-medication titration was 3- to 4-fold more broad-ranging than i.m. medication titration, (b) oral placebo was titrated to the same extent as the oral investigational drugs, and (c) the titration schedule did not follow protocol requirements. Moreover, the average doses in all drug and placebo groups were the same. Concomitant medication like sleep inducers was found to be more closely related to doctors' habits than to actual medical need. Independent of trial and investigational drug, 10-33% of all patients received additional sleep inducers.

Administration, Oral↗
PubMed1987

The role of titratable acidity in acid aerosol-induced bronchoconstriction.

We evaluated the importance of pH, titratable acidity, and specific chemical composition in acid aerosol-induced bronchoconstriction in 8 asthmatic subjects. We administered aerosols of HCl and H2SO4 at pH 2.0 in an unbuffered state and buffered with glycine. The buffered acids were given in order of increasing titratable acidity (defined as the number of ml of 1 N NaOH required to neutralize 100 ml of acid solution to pH 7.0). Each set of buffered or unbuffered acid aerosols was given on a separate day and each aerosol was inhaled through a mouthpiece during 3 min of tidal breathing. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw) before and after inhalation of each aerosol. SRaw increased by more than 50% above baseline in 1 of 8 subjects after inhalation of unbuffered HCl and in no subjects after inhalation of unbuffered H2SO4, even at pH 2.0. In contrast, SRaw increased by greater than 50% in all 8 subjects after inhalation of HCl and glycine at pH 2.0 and 7 of 8 subjects after inhalation of H2SO4 and glycine at pH 2.0. The mean titratable acidity required to increase SRaw by 50% above baseline was calculated for each challenge by linear interpolation; these values for H2SO4 and glycine (5.1 ml of 1 N NaOH) and HCl and glycine (2.2 ml of 1 N NaOH) were slightly, but significantly, different (p = 0.01) and were considerably higher than the titratable acidity of the unbuffered acids at pH 2 (1.0 ml of 1 N NaOH).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1967

Glucose titration studies in patients with chronic progressive renal disease.

Glucose titration studies were performed on 17 patients with either chronic pyelonephritis or chronic glomerulonephritis. Glomerular filtration rates for the group ranged from 4.3 to 58.1 ml per minute. In none of the patients in whom the glomerular filtration rate was over 15 ml per minute was there appreciable splay, and the mean titration curve for these patients resembled that obtained by Smith and associates in normal man (1). In half of this group of eight patients, GFR ranged from 16.6 to 22.7 ml per minute; in the other half values ranged from 42.3 to 58.1 ml per minute. Yet, the mean titration curves were identical for the two groups. In addition, no difference was observed in the titration curves for patients with pyelonephritis and those with glomerulonephritis. In patients with GFR values below 15 ml per minute, increased splay was observed, and below a GFR of 10 ml per minute, the splay was very marked. Both the absence of exaggerated splay in patients with reduction of glomerular filtration rate by as much as 85%, and the emergence of exaggerated splay in patients with more marked reduction of GFR, require explanation. Theoretical considerations are presented in the text.

Adolescent↗
PubMed1989

Difference in amounts between titratable acid and total carboxylic acids produced by oral streptococci during sugar metabolism.

The acid produced by the resting cells of Streptococcus mutants NCTC 10449 and HS 6 and S. sanguis ATCC 10556 during sugar metabolism was estimated with a pH-stat and a carboxylic acid analyzer. Lactic, formic, acetic, pyruvic, and carbonic acids were detected in the reaction mixtures, but propionic, citric, succinic, iso-butyric, butyric, iso-valeric, and valeric acids were not detected. The amount of titratable acid estimated by alkaline titration with the pH-stat was larger than the amount of total carboxylic acids estimated with the carboxylic acid analyzer. The difference in quantity between the titratable and the total carboxylic acids increased significantly with an increase in the period of incubation with sugar. Moreover, the value of the alkaline titration of standard lactic, formic, acetic, and pyruvic acids was equal to the amount analyzed with the carboxylic acid analyzer. The results indicated that these two streptococci produced not only these carboxylic acids but also other acid(s), possibly non-carboxylic acid(s), during their sugar metabolism.

Carboxylic Acids↗
PubMed2006

Comparison of lentiviral vector titration methods.

BACKGROUND: Lentiviral vectors are efficient vehicles for stable gene transfer in dividing and non-dividing cells. Several improvements in vector design to increase biosafety and transgene expression, have led to the approval of these vectors for use in clinical studies. Methods are required to analyze the quality of lentiviral vector production, the efficiency of gene transfer and the extent of therapeutic gene expression. RESULTS: We compared lentiviral vector titration methods that measure pg p24/ml, RNA equivalents/ml, transducing units (TU/ml) or mRNA equivalents. The amount of genomic RNA in vector particles proves to be reliable to assess the production quality of vectors encoding non-fluorescent proteins. However, the RNA and p24 titers of concentrated vectors are rather poor in predicting transduction efficiency, due to the high variability of vector production based on transient transfection. Moreover, we demonstrate that transgenic mRNA levels correlate well with TU and can be used for functional titration of non-fluorescent transgenes. CONCLUSION: The different titration methods have specific advantages and disadvantages. Depending on the experimental set-up one titration method should be preferred over the others.

Chromosome Mapping↗
PubMed2004

The significance of controlled conditions in lentiviral vector titration and in the use of multiplicity of infection (MOI) for predicting gene transfer events.

BACKGROUND: Although lentiviral vectors have been widely used for in vitro and in vivo gene therapy researches, there have been few studies systematically examining various conditions that may affect the determination of the number of viable vector particles in a vector preparation and the use of Multiplicity of Infection (MOI) as a parameter for the prediction of gene transfer events. METHODS: Lentiviral vectors encoding a marker gene were packaged and supernatants concentrated. The number of viable vector particles was determined by in vitro transduction and fluorescent microscopy and FACs analyses. Various factors that may affect the transduction process, such as vector inoculum volume, target cell number and type, vector decay, variable vector - target cell contact and adsorption periods were studied. MOI between 0-32 was assessed on commonly used cell lines as well as a new cell line. RESULTS: We demonstrated that the resulting values of lentiviral vector titre varied with changes of conditions in the transduction process, including inoculum volume of the vector, the type and number of target cells, vector stability and the length of period of the vector adsorption to target cells. Vector inoculum and the number of target cells determine the frequencies of gene transfer event, although not proportionally. Vector exposure time to target cells also influenced transduction results. Varying these parameters resulted in a greater than 50-fold differences in the vector titre from the same vector stock. Commonly used cell lines in vector titration were less sensitive to lentiviral vector-mediated gene transfer than a new cell line, FRL 19. Within 0-32 of MOI used transducing four different cell lines, the higher the MOI applied, the higher the efficiency of gene transfer obtained. CONCLUSION: Several variables in the transduction process affected in in vitro vector titration and resulted in vastly different values from the same vector stock, thus complicating the use of MOI for predicting gene transfer events. Commonly used target cell lines underestimated vector titre. However, within a certain range of MOI, it is possible that, if strictly controlled conditions are observed in the vector titration process, including the use of a sensitive cell line, such as FRL 19 for vector titration, lentivector-mediated gene transfer events could be predicted.

Journal Article↗
PubMed2003

Gastric intramucosal pH is stable during titration of positive end-expiratory pressure to improve oxygenation in acute respiratory distress syndrome.

BACKGROUND: Optimal positive end-expiratory pressure (PEEP) is an important component of adequate mechanical ventilation in acute lung injury and acute respiratory distress syndrome (ARDS). In the present study we tested the effect on gastric intramucosal pH of incremental increases in PEEP level (i.e. PEEP titration) to improve oxygenation in ARDS. Seventeen consecutive patients with ARDS, as defined by consensus criteria, were included in this clinical, prospective study. All patients were haemodynamically stable, and were not receiving vasopressors. From an initial level of 5 cmH2O, PEEP was titrated at 2 cmH2O increments until the partial arterial oxygen tension was 300 mmHg or greater, peak airway pressure was 45 cmH2O or greater, or mean arterial blood pressure decreased by 20% or more of the baseline value. Optimal PEEP was defined as the level of PEEP that achieved the best oxygenation. The maximum PEEP was the highest PEEP level reached during titration in each patient. RESULTS: Gastric mucosal pH was measured using gastric tonometry at all levels of PEEP. The thermodilution technique was used for measurement of cardiac index. Gastric mucosal pH was similar at baseline and at optimal PEEP levels, but it was slightly reduced at maximum PEEP. Cardiac index and oxygen delivery remained stable at all PEEP levels. CONCLUSION: Incremental titration of PEEP based on improvement in oxygenation does not decrease gastric intramucosal perfusion when cardiac output is preserved in patients with ARDS.

Adolescent↗