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PubMed2003

A thermodynamic analysis of the hydrogen ion titration of micelles.

A thermodynamic analysis of hydrogen ion titration is presented for association colloids with particular emphasis on surfactant micelles. When a particular type of the micellar Gibbs-Duhem relation (MGD), alpha(M)dmu(I)+(1-alpha(M))dmu(N)=0 [alpha(M): the degree of ionization of micelles; mu(I),mu(N): chemical potentials of ionized and nonionized species], holds, the free energy change accompanying the ionization of the micelle G(ex) can be evaluated from the titration data in the same manner as for covalently bonded colloids such as linear polyions. In the case where the regular solution approximation is valid for mixed micelles, the titration curve should be a straight line with a slope yielding the interaction parameter, and G(ex) is given as a function of alpha(M)(2). For dodecyldimethylamine oxide micelles for which the MGD relation has been shown to hold, values of the calculated electrostatic free energy G(el) were close to but significantly greater than experimental G(ex) values when the former were calculated on the basis of the Poisson-Boltzmann equation for either a sphere or a plate with smeared charges in a salt solution of infinite volume. When the critical micelle concentration (cmc) data are combined with the hydrogen ion titration data, we obtain a criterion to judge whether the above MGD relation holds or not. When the MGD relation holds, the monomer concentration C(1) can be evaluated from the hydrogen ion titration. For most cases examined, the C(1)/C(1)(alpha(M)=0) from the titration agrees well with cmc/cmc(alpha(M)=0), suggesting cmc=C(1) above the cmc. For tetradecyldimethylamine oxide, the MGD relation does not hold in the range of low ionic strength and even at 0.1 M NaCl it has been found that C(1)/C(1)(alpha(M)=0)<cmc/cmc(alpha(M)=0), due probably to enormous micelle growth.

Journal Article↗
PubMed2003

A novel method for the titration of recombinant virus stocks by ELISPOT assay.

The development of vectors for gene therapy requires the definition of quality control parameters such as titration, contamination, transduction efficiency and biological effects in defined model systems. For most viral vectors, the classical titration by plaque formation is not applicable, because vectors are defective for replication and packaging cell lines are not always available. In particular, for vectors derived from the autonomous parvovirus MVM(p), the titration method used currently is based on the amplification of the viral genome inside an infected cell, which can then be revealed with a specific radioactive probe (J. Virol. 63 (1989) 1023). In situ hybridization allows to titrate wild-type virus as well as vectors, using probes that are specific for the substituted viral genes or for the transgene, respectively. This method is, however, time consuming, making the simultaneous titration of large numbers of samples difficult. The use of a radioactive probe requires an adequate facility. An ELISPOT method that allows for rapid titration of up to 23 vector stocks in one 96 well dish was devised. This method is based on the actual expression of the transgene. Compared to in situ hybridization, titers obtained by the ELISPOT method were in general equivalent or higher. However, for some vector stocks the ELISPOT titers were repeatedly lower, indicating that in situ hybridization does not give an accurate measure of transducing units. Our model system is recombinant parvovirus MVM expressing human IL2, but the method should be adaptable to other vectors expressing transgenes that are secreted and for which antibodies are available.

Cell Line↗
PubMed2002

Cyclic alternating pattern and positive airway pressure titration.

OBJECTIVE: To demonstrate that stability of the upper airway during continuous positive airway pressure (CPAP) titration is influenced by the microstructure of sleep as defined by the cyclic alternating pattern (CAP). METHODS: Retrospective review of 12 CPAP titration records. The patterns of flow-limitation during CPAP at subtherapeutic pressures were characterized as 'stable' (persistent and non-progressive inspiratory flow limitation) or 'unstable' (progressive increase in inspiratory flow-limitation terminating in an arousal), and continuous periods of at least 10 min were identified. Sleep stage scoring by both conventional Rechtshaffen and Kales criteria and the CAP were done. The relationship between flow type and CAP was determined. Responses to an increase in applied pressure on flow-limitation were noted. RESULTS: There were a total of 50 periods fulfilling the above criteria, totaling 1113 min of titration time. Thirty periods (757 min, 68% of total) showed a stable flow-limitation pattern. A total of 29/30 periods showing a stable flow pattern during sleep was scored as non-CAP, and only a single 18-min period of stable flow was scored as CAP. A total of 19/20 periods showing an unstable flow pattern was in sleep with CAP characteristics, the exception being a single 14-min period where unstable flow was noted in non-CAP. Flow-limitation was stable and non-progressive or absent during non-CAP, even at less than optimal pressures. This was noted irrespective of the presence or absence of delta sleep as scored by conventional criteria. Pressure increases during non-CAP, when the profile of the inspiratory flow was flattened, never resulted in a discernable change in the flow profile, while at least two-thirds of pressure increments during CAP periods improved flow. CONCLUSIONS: The microstructure of sleep as determined by CAP and non-CAP have practical implications for manual pressure titration algorithms and research on upper airway physiology during sleep. The appearance of a period of non-CAP, irrespective of conventionally scored delta sleep, may falsely suggest that the CPAP is optimal or close to it. Large increases in non-CAP that may be seen during a titration night can reduce the window of opportunity for titration. Increases in CPAP should be avoided in non-CAP.

Journal Article↗
PubMed2000

Continuous on-line true titrations by feedback-based flow ratiometry. The principle of compensating errors

We introduce a new concept for continuous on-line titrations based on feedback-controlled flow ratiometry and the principle of compensating errors. The system has been thoroughly tested by applying it to acid-base neutralization titrations with indicator-based end point detection. In a typical case, the total flow (FT, consisting of the sample and the titrant flows) is held constant while the titrant (e.g., a standard base containing an indicator) flow FB varies linearly in response to a controller output voltage. The sample (e.g., an acidic solution to be titrated) flow FA constitutes the makeup and thus also varies (FA = FT - FB). The status of the indicator color in the mixed stream is monitored by an optical detector and used either for governing the controller output or for interpreting the results of the titration. Three methods (PID based control, fixed triangular wave control, and feedback-based triangular wave control implemented on a PC) were examined. In the last and the most successful approach, the titrant flow is initially ramped upward linearly. At the instant a change in the color is sensed by the detector, the titrant flow rate FH is higher than the true equivalence flow rate FE because of the lag time between the first compositional change and its detection. The sensing of the change in color causes the system output to immediately reverse its ramp direction such that the titrant flow now goes down linearly at the same rate. At the instant a change in color, in the opposite direction this time, is again sensed, the titrant flow rate FL is lower than FE by exactly the same amount that FH was higher than FE. This principle of compensating errors (FE = (FH + FL)/2) allows true titrations with excellent reproducibility and speed (0.6% RSD at 3 s/titration and 0.2% RSD at 10 s/titration) and titrant volume consumption as little as 12 microL/titration and solves an old conceptual problem in flow based titrations.

Journal Article↗
PubMed1996

Multicomponent NMR titration for simultaneous measurement of relative pKaS.

An NMR titration method has been developed to simultaneously measure the difference in acid dissociation constants (delta pKa) of two or more compounds with high precision and accuracy. The delta pKa between the conjugate acids of the two stereoisomers of 4-tert-butylcyclohexylamine 1 was determined in a single 1H NMR titration experiment. A mixture of the two stereoisomers was titrated with DCI in a 3:1 (v/v) mixture of CD3OD/D2O. From the variations of the H1 chemical shifts the ratio of the acidity constants was determined. The trans stereoisomer 1t was found to be the more basic by 0.121 +/- 0.002 pK unit. A repeat titration in DMSO-d6 also found 1t to be the more basic, by 0.217 +/- 0.003 pK unit. The delta pKa between the two stereoisomers of 4-tert-butylcyclohexanecarboxylic acid 2 was determined in both of these solvents using 1H and 13C NMR. Thermodynamic parameters delta delta H degree and delta delta S degree were evaluated from the temperature dependence of delta pKa. To further demonstrate the utility of this method, the delta pKas of the conjugate acids of the four stereoisomers of 2-decalylamine 3 were determined in a single 1H NMR titration experiment. The cis,cis stereoisomer (3cc) was found to be the most basic, with the cis,trans (3ct), trans,cis (3tc), and trans,trans (3tt) less basic by 0.012 +/- 0.003, 0.037 +/- 0.004, and 0.141 +/- 0.005 pK unit, respectively. A second four-component titration was also performed with the two 4-tert-butylcyclohexylamines (1) and the two trans-2-decalylamines (3tc, 3tt).

Cyclohexylamines↗
PubMed1977

Oxidative titrations of reduced cytochrome aa3: anisotropic extinction behavior observed in the heme alpha-band region.

Direct chemical titrations of reduced, purified cytochrome aa3 were monitored at 604 nm. Anaerobic oxidation by potassium ferricyanide or 1,1'-bis(hydroxymethyl)-ferricinium ion was compared with the natural substrate, molecular oxygen. The four electrons from reduced cytochrome aa3 were donated to one oxygen molecule, resulting in a linear titration with only fully oxidized or fully reduced enzyme molecules present. Unlike the linear or sigmoidal titrations which resulted from various reductive titrations reported previously, pronounced hyperbolic curves were obtained with the chemical oxidants. The midpoint potential values exhibited by the four metal centers of cytochrome aa3 were determined by computer simulation of the titration curves. A high potential pair of components (heme a = 340 mV, Cu = 340 mV) and a low potential pair (heme a = 220 mV, Cu = 240 mV) were observed, consistent with literature values. Unique to these equilibrium studies was a split in the heme a extinction coefficients at 604 nm. The low potential heme a component contributed 80-85% to the total absorbance change. A polarographic assay was used to verify that the integrity of cytochrome aa3 remained intact during equilibrium titrations spanning several hours. These experimental results indicate that simple chemical reversibility does not exist for cytochrome aa3 under anaerobic conditions.

Anaerobiosis↗
PubMed2006

Titration of fatty acids solubilized in cationic and anionic micelles. Calorimetry and thermodynamic modeling.

The electrostatic properties of charged surfactant micelles are investigated through titrations of fatty acid probes solubilized in the micelles. The titration process is followed by means of calorimetric measurements and by determining the pH values as a function of added base. This approach yields a complete thermodynamic description of the titration process. In particular, we find that the process is endothermic at 298 K. This is contrary to the titration of carboxylic acids in water, where DeltaH is approximately 0. To identify the main effect underlying the difference in DeltaH between titration in a micelle and water, a thermodynamic model has been developed which focuses on the transfer properties of charged and uncharged species from bulk water to the surface of a micelle and which incorporates a dielectric discontinuity at the micellar surface. The model relies on the use of the Poisson-Boltzmann equation which is solved using a finite element method. Experimental results and the model calculations imply that the dielectric discontinuity at (or near) the micellar surface plays a major role and hence must be included when analyzing the titration behavior of an acid functionality at the surface of a charged micelle.

Journal Article↗
PubMed1999

Vital signs and nurses' choices of titrated dosages of intravenous morphine for relieving pain following cardiac surgery.

Postoperative pain, if unrelieved, will impede patients' recovery. A theoretical model of factors which influence nurses' choices of titrated dosages of intravenous (IV) morphine was constructed for this study. This study aimed to examine whether or not a patient's vital signs would influence nurses' choices of titrated dosages of IV morphine for relieving pain following cardiac surgery. A survey design with a vignette and questionnaire method was used to collect data. The vignette developed by McCaffery & Ferrell was modified and adapted for this study. It described the pain reports and vital signs of two patients on postoperative day 1 following cardiac surgery. Convenience sampling was used to seek voluntary participation from 29 registered nurses working in the cardio-thoracic intensive care unit of a private hospital in Sydney, Australia. A protocol of the unit allowed nurses to titrate IV morphine against the pain of patients following cardiac surgery. The results showed that the pain assessment of the two patients in the vignette documented by the nurses were not consistent. The titrated dosages (a bolus dosage and a maintenance dosage) chosen by the nurses for the patient with slightly elevated vital signs differed significantly from the titrated dosages chosen by the same group of nurses for another patient with vital signs at the lower end of the stable range (t=3. 33, d.f.=25, P < 0.01 for a bolus dosage and t=3.73, d.f.=25, P < 0. 01 for a maintenance dosage). Different risk factors were stated by the nurses in titrating the bolus and maintenance dosages of IV morphine. The importance of accepting patients' verbal reports of pain as well as the provision of optimal dosages of IV morphine for pain relief is highlighted. A disadvantage of using a vignette and questions method is that the patients' clinical status is somewhat unreal. Further studies, however, were also recommended.

Adult↗
PubMed1994

Salt-induced formation of the molten globule state of cytochrome c studied by isothermal titration calorimetry.

Although the molten globule state has been proposed as a major intermediate of protein folding, it has proven difficult to obtain thermodynamic data characterizing this state. To explore another approach for characterizing the molten globule state, salt-induced formation of the molten globule state of horse cytochrome c at pH 1.8 was studied by isothermal titration calorimetry. By titrating the acid-unfolded cytochrome c with sodium perchlorate, an exothermic reaction was observed. The titration curve obtained from the heat was cooperative and agreed well with the conformational transition curve measured by CD at 222 nm. This result indicated that the salt-induced conformation change is well approximated by a two-state transition between the acid-unfolded and molten globule states. The heat for formation of the molten globule state estimated by isothermal titration calorimetry was consistent with the enthalpy change for unfolding of the sodium perchlorate-stabilized molten globule state at pH 1.8, which was measured by differential scanning calorimetry and CD. These results indicate that the heat of titration largely reflects the enthalpy change of the conformational transition. From these results, we consider that isothermal titration calorimetry will become a useful approach for investigating the molten globule state.

Animals↗
PubMed2006

Acid titrations of poly(dG-dC).poly(dG-dC) in aqueous solution and in a w/o microemulsion.

The model polynucleotide poly(dG-dC).poly(dG-dC) (polyGC) was titrated with a strong acid (HCl) in aqueous unbuffered solutions and in the quaternary w/o microemulsion CTAB/n-pentanol/n-hexane/water. The titrations, performed at several concentrations of NaCl in the range 0.005 to 0.600 M, were followed by recording the modifications of the electronic absorption and of the CD spectra (210< or = lambda < or =350 nm) upon addition of the acid. In solution, the polynucleotide undergoes two acid-induced transitions, neither of which corresponds to denaturation of the duplex to single coil. The first transition leads to the Hoogsteen type synG.C+ duplex, while the second leads to the C+.C duplex. The initial B-form of polyGC was recovered by back-titration with NaOH. The apparent pKa values were obtained for both steps of the titration, at all salt concentrations. A reasonably linear dependence of pKa1 and pKa2 from p[NaCl] was obtained, with both pKa values decreasing with increasing ionic strength. In microemulsion, at salt concentrations < or = 0.300 M, an acid-induced transition was observed, matching the first conformational transition recorded also in solution. However, further addition of acid led to denaturation of the protonated duplex. Renaturation of polyGC was obtained by back-titration with NaOH. At salt concentrations > 0.300 M, polyGC is present as a mixture of B-form and psi- aggregates, that slowly separate from the microemulsion. The acid titration induces at first a conformational transition similar to the one observed at low salt or in solution, then denaturation occurs, which is however preceded by the appearance of a transient conformation, that has been tentatively classified as a left-handed Z double helix.

Circular Dichroism↗
PubMed1975

Titration study of acetylated lysozyme.

To study the interaction between carboxyl groups and amino groups in native lysozyme [EC 3.2.1.17], and to identify the positions and the pK values of the abnormal carboxyl groups, N-acetylated lysozyme was prepared. The acetylation did not affect the molecular shape of the enzyme, but changed six amino groups to a non-ionizable form, leaving one amino group free; this was determined to be Lys 33. In addition, pH titration of the acetylated lysozyme in 0.2 or 0.02 M KCl aqueous solution indicated fewer titratable groups with pK(int) of 7.8 or 10.4 compared with the native protein, though the number of titratable carboxyl groups was not affected by the acetylation. From the pH titration results and structural considerations, the unititratable carboxyl groups were suggested to be Asp 48, Asp 66, and Asp 87. On the other hand, spectrophotometric titration in 0.2 M KCl showed that all three tyrosine residues are titratable in the acetylated protein, although an abnormal tyrosine residue exists in the native state. Tyr 20 was suggested to be untitratable in the pH range of 8-12.6.

Acetylation↗
PubMed1981

Hydrogen-tritium exchange and nuclear magnetic resonance titrations of the histidine residues in ribonuclease St and analysis of their microenvironment.

Ribonuclease St consists of 101 amino acid residues in a single polypeptide chain with one disulfide bond. It has two histidines located at positions 60 and 91 from the amino terminus. The pKa values of His-60 and His-91 were estimated by hydrogen-tritium exchange titration to be 8.0 and 6.3, respectively, and these values were confirmed by 1H NMR titration. The high pKa value of His-60 suggests that it interacts with a neighboring negative charge, presumably of a carboxylate. This is suggested by the presence of an inflection at pH 4.5 in the 1H NMR titration plot for His-60. The 1H-NMR titration plot for His-91 also suggests its interaction with a carboxylate, although the pKa of His-91 was close to that of unperturbed histidine residues. This suggests that a positively charged group is also located in the vicinity of His-91. It was concluded that His-91 is one of the active site residues of the enzyme. The pKa for His-91 was shifted to the alkaline side in the presence of 3'-GMP, a competitive inhibitor, in the titration plots observed by both hydrogen-tritium exchange and 1H NMR spectroscopy. The 31P NMR titration data suggest that in the 3'-GMP-RNase St complex the dianion form of the nucleotide participates in the interaction with the protonated form of His-91. The existence of another positively charged group with pKa of 7.0 was also suggested on the basis of the 31P NMR data.

Amino Acid Sequence↗
PubMedDate not supplied

Quick titration of pergolide in cotreatment with domperidone is safe and effective.

The purpose of the study was to analyze efficacy and safety of quick pergolide titration combined with domperidone. In an open-label prospective study, pergolide was titrated in 16 days to a maximum of 3 mg/d doses as adjunctive treatment to L-Dopa in 10 elderly patients with Parkinson's disease. Sixty milligrams domperidone was started 2 days before and and continued during the pergolide titration period to prevent side effects. Adverse events were studied for 6 weeks. Efficacy was measured with the motor part ("on" condition) of the Unified Parkinson's Disease Rating Scale (UPDRS), the 2-minute walking test, the Timed Up and Go test, and the Postural-Locomotor-Manual test. After quick titration of pergolide with domperidone cotreatment, no symptomatic side effects were seen except for lightheadedness in one patient, which disappeared after dose reduction. The UPDRS motor score improved significantly from 21 +/- 8 at baseline to 16 +/- 7 and 12 +/- 7 after 1 and 2 weeks, respectively. The 2-minute walking distance improved significantly from 123 +/- 36 m at baseline to 136 +/- 41 m after 6 weeks. The Timed Up and Go and Postural-Locomotor-Manual test results, overall, did not show significant changes. Quick titration of pergolide to a maximum of 3 mg/d with domperidone cotreatment is safe and effective. Therefore, we recommend domperidone cotreatment in the titration period to prevent unnecessary failure of dopamine agonist treatment because of adverse effects.

Aged↗
PubMed2002

Tolerability of beta-blocker initiation and titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF).

BACKGROUND: beta-Blockade improves survival when administered over a long period of time to patients with heart failure. However, the time course of any possible deterioration during the titration phase has not been reported. METHODS AND RESULTS: We looked at evidence of clinical deterioration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) by analyzing events and symptoms during the first 90 days. During titration, the Kaplan-Meier curves for the combined end point of all-cause mortality/all-cause hospitalization were similar in all patients randomized, with no significant difference in favor of placebo at any visit or in any of the analyzed subgroups (New York Heart Association class II, III/IV, or III/IV with ejection fraction <0.25, heart rate less-than-or-equal 76 bpm, and systolic blood pressure less-than-or-equal 120 mm Hg). The curves started to diverge in favor of beta-blockade after 60 days. Low heart rate was the main factor that limited titration. In New York Heart Association class III/IV, 5.9% of the patients receiving placebo discontinued study medicine during the first 90 days compared with 8.1% of those receiving metoprolol CR/XL (P=0.037 unadjusted, P=NS adjusted); corresponding figures in those with New York Heart Association class III/IV and ejection fraction <0.25 were 7.1% and 8.0% (P=NS). From day 90 until the end of the study, more patients in the placebo group discontinued study medicine in all subgroups. There was no change in diuretic or ACE inhibitor dosing with beta-blocker titration. Most patients reported no change in symptoms of breathlessness or fatigue during the titration phase. CONCLUSIONS: When carefully titrated, metoprolol CR/XL can be given safely to the overwhelming majority of patients with stable mild to moderate heart failure, with minimal side effects or deterioration.

Adrenergic beta-Antagonists↗
PubMed1999

Clinical application of the forced oscillation technique for CPAP titration in the sleep apnea/hypopnea syndrome.

We have previously demonstrated that upper airway obstruction in sleep apnea/hypopnea syndrome (SAHS) can be accurately assessed in real-time by measuring respiratory impedance (|Z|) with the forced oscillation technique (FOT). The aims of the present study were: (1) to determine the feasibility of identifying the optimal continuous positive airway pressure (CPAP) for patients with SAHS based on analysis of the |Z| signal during conventional polysomnographic CPAP titration studies; and (2) to evaluate practical issues involved in the application of FOT during CPAP titration. We performed CPAP titration in 28 patients with SAHS during polysomnography (PSG) (14 nap and 14 full overnight studies) using a FOT system applied continuously to obtain an on-line measurement of |Z|. FOT was easily implemented and was well-tolerated by the patients. Optimal CPAP levels were determined both in the conventional manner from the standard PSG titration record and during a separate blinded analysis using the FOT signal alone. The mean conventional versus FOT-based optimal CPAP values were similar for both nap studies (10.6 +/- 0.6 [mean +/- SEM] versus 11.1 +/- 0.6 cm H(2)O, respectively, p = 0. 054) and overnight studies (9.9 +/- 0.7 versus 9.9 +/- 0.6 cm H(2)O, respectively, p = 1.00). Subsequent analysis of the PSG record with the FOT signal incorporated demonstrated that artefacts in the |Z| tracing occurred during mask leak, mouth breathing, and movement during arousal. Such abnormalities were readily identified from the flow tracing. These results indicate that, for adequate interpretation, the tracing and values of respiratory impedance obtained by FOT should be evaluated in conjunction with the flow signal. Continuous FOT-guided CPAP titration is feasible and may be a useful adjunct during manual titration. FOT could also potentially serve as the basis for automated CPAP in SAHS.

Humans↗
PubMed2001

Titration emulation: a computer-assisted technique that simplifies the quantification of anti-dsDNA antibodies using the Crithidia luciliae assay.

Titers of anti-double-stranded (ds) DNA antibodies in sera from patients with systemic lupus erythematosus (SLE) using the Crithidia luciliae assay method were compared by conventional titration vs the titration emulation method (ImageTiter) to evaluate whether the latter assay can replace manual titration. Titers by the two methods were identical or within one dilution in 98% (41/42) of samples. A single sample showed a two-dilution difference. Titration emulation showed a tendency to under-estimate the titer of high titer anti-dsDNA samples, although the difference was small. Titration emulation is a suitable alternative to the conventional titration method, offering an accurate and cost-effective approach to quantification of anti-dsDNA antibodies.

Animals↗
PubMed2003

Evaluation of unattended automated titration to determine therapeutic continuous positive airway pressure in patients with obstructive sleep apnea.

BACKGROUND: Determination of the therapeutic pressure during continuous positive airway pressure (CPAP) therapy is usually performed by a technician during polysomnography. In recent years, several devices for automated adjustment of the therapeutic pressure by the means of computerized algorithms were developed. The aims of the present study were to compare two different devices for automated titration and to verify if unattended automated titration is a feasible strategy to determine the therapeutic CPAP. METHODS: We enrolled 16 consecutive patients with obstructive sleep apnea syndrome (OSAS) defined by an apnea-hypopnea index > 20/h. Automated titration was performed in the hospital using two CPAP devices (Autoset; Resmed; North Ryde, Australia; and Somnosmart; Weinmann; Hamburg, Germany) in random order for 2 consecutive nights, based on different signals for the detection of respiratory events. During titration, there was no direct supervision by a technician, and polysomnography was not recorded. We defined the therapeutic pressure as the 95th percentile of the airway pressure over time (P95). RESULTS: We observed significant differences of the P95 between the two devices, with an average of 7.0 +/- 2.5 cm H(2)O for the Somnosmart and 9.9 +/- 2.6 cm H(2)O for the Autoset (p = 0.005) [mean +/- SD]. There was a considerable lack of agreement between the two devices, with a bias of 3.0 cm H(2)O and limits of agreement ranging from + 9.3 to - 3.2 cm H(2)O. We found no significant correlation between the paired differences of P95 and either indexes of severity of OSAS or lung function variables. CONCLUSION: Automated titration based on the analyses of flow (Autoset) or forced oscillations (Somnosmart) predicted significant different therapeutic pressures for fixed CPAP therapy. Thus, unattended automated titration performed during 1 night of hospital stay with commercially available devices cannot be used to determine accurately the therapeutic CPAP in patients with OSAS.

Automation↗
PubMed2005

Individual titration for maximal blockade of the renin-angiotensin system in proteinuric patients: a feasible strategy?

Agents that interfere with the renin-angiotensin system (RAS) reduce proteinuria and afford renal protection. The combination of different measures that serve maximization of RAS blockade is thought to improve the antiproteinuric efficacy. The feasibility and the efficacy of such a combination strategy were studied in nondiabetic patients with residual proteinuria during previous RAS blockade by individual antiproteinuric titration. Previous medication was replaced by irbesartan 300 mg combined with a diuretic. Lisinopril was added in increasing doses until a maximal dose of 40 mg/d. Titration stopped when target proteinuria (< 1 g/d) was reached or further dose titration was not tolerated because of side effects. Residual proteinuria (median, 3.2 g/d; 95% confidence interval, 1.8 to 5.2 g/d) was significantly reduced with 55.6% (95% confidence interval, 16.0 to 73.2%; P < 0.02) on the maximal additional tolerated dose of lisinopril. The maximal dose of lisinopril was 10 mg in two of eight, 20 mg in two of eight, 30 mg in one of eight, and 40 mg in three of eight patients. At this dose, target proteinuria of < 1 g/d was reached in two of eight patients. The number of patients with adverse events during dose titration was five of eight patients: two had cough; two had hyperkalemia (> 5.5 mmol/L), one of whom had > 50% increase of serum creatinine; and one had dizziness. In conclusion, individual titration for maximal RAS blockade, entailing dose titration of angiotensin-converting enzyme inhibitors on top of high-dose angiotensin II antagonists with diuretic, induces further reduction of residual proteinuria. However, this occurs at the expense of adverse events. To further improve renoprotective treatment strategies, it is important to explore other modes of antiproteinuric intervention in patients with residual proteinuria during RAS blockade.

Adolescent↗