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Results of trabeculectomy with 0.3 mg/ml mitomycin C titrating exposure times based on risk factors for failure.

PURPOSE: To examine the efficacy of trabeculectomy with mitomycin C 0.3 mg/ml using titrated exposure times. METHODS: A retrospective chart review of consecutive patients undergoing trabeculectomy in an academic referral glaucoma clinic was performed. All patients received trabeculectomies performed by one surgeon (M.B.S.). The study included 57 eyes of 57 patients using mitomycin C with exposure times titrated from one to five minutes based on risk factors for trabeculectomy failure. Surgical success was defined as a final intraocular pressure (IOP) of less than 21 mmHg with or without medications or a 25% reduction in IOP if preoperative IOP was 21 mmHg or less. Patients requiring repeat trabeculectomies were considered failures regardless of their final IOP. Patients receiving different mitomycin C exposure times were compared but statistical analysis was not used because these subgroups were not randomized. RESULTS: An overall surgical success rate of 84.2% was achieved at a mean follow-up of 11.9 months. The surgical success rate and percentage IOP reduction was similar between exposure time subgroups. Hypotonous maculopathy observed in three patients (5.3%). All cases of hypotonous maculopathy was occurred in the lower-risk patients receiving one to three minute exposure times to mitomycin C. CONCLUSIONS: We believe mitomycin C should be used sparingly if at all in patients at lower risk for trabeculectomy failure. This concentration of mitomycin C with four to five minute exposure times appears to be efficacious for patients with multiple risk factors for trabeculectomy failure.

Administration, Topical↗

Comparative effects of felodipine ER, amlodipine and nifedipine GITS on 24 h blood pressure control and trough to peak ratios in mild to moderate ambulatory hypertension: a forced titration study.

OBJECTIVE: To evaluate the 24 h antihypertensive efficacy and duration of action of felodipine extended release (ER) in comparison with two other long acting dihydropyridine calcium antagonists, amlodipine and nifedipine gastrointestinal therapeutic system (GITS), in patients with mild to moderate essential hypertension substantiated by ambulatory blood pressure (BP) monitoring. DESIGN: Randomized, forced titration, parallel group study. Clinic BP was measured at every patient's visit, and 24 h ambulatory BP was monitored at baseline and at the end of each dose-titration period. SETTING: Single centre: hypertension research unit in Quebec City, Quebec. PATIENTS: There were 89 patients enrolled into the study. Eighty-four eligible patients were randomized, and 83 completed the study and were included in the final efficacy analysis. INTERVENTIONS: Following a two-to four-week washout period (baseline), patients were randomly allocated to receive felodipine ER 5 mg, amlodipine 5 mg or nifedipine GITS 30 mg for four weeks (low dose). All study patients had their daily dose doubled to felodipine ER 10 mg, amlodipine 10 mg or nifedipine GITS 60 mg for a further four weeks (high dose). MAIN RESULTS: Significant (P < 0.001) and similar changes from baseline in clinic BP were observed in all treatment groups for low and high doses. Ambulatory BP profiles showed comparable blood pressure reductions with felodipine ER and amlodipine, and a trend towards a lesser reduction with nifedipine GITS during 24 h, daytime and night-time periods. BP loads were similarly reduced with the three treatments. Trough to peak ratios (T:Ps) were calculated from 24 h ambulatory BP curves according to two different approaches: for diastolic and systolic BP, respectively, the global approach produced T:Ps of 0.49 and 0.50 with felodipine ER 5 mg; 0.50 and 0.34 with felodipine ER 10 mg; 0.70 and 0.60 with amlodipine 5 mg; 0.88 and 0.82 with amlodipine 10 mg; 0.65 and 0.55 with nifedipine GITS 30 mg; 0.68 and 0.53 with nifedipine GITS 60 mg. T:Ps in the individual approach were 0.07 and 0.10 with felodipine ER 5 mg; 0.23 and 0.31 with felodipine ER 10 mg; 0.22 and 0.31 with amlodipine 5 mg; 0.45 and 0.58 with amlodipine 10 mg; 0.27 and 0.31 with nifedipine GITS 30 mg; and 0.24 and 0.40 with nifedipine GITS 60 mg. CONCLUSION: There was no evidence in this study of a difference among felodipine ER, amlodipine and nifedipine GITS in lowering ambulatory or clinic BP. Treatment based on ambulatory BP may be preferable to treatment guided by T:Ps because ambulatory BP is firmly established as a predictor of cardiovascular risk. Furthermore, there is no consensus on how to calculate T:Ps, and different methods of calculation may give divergent results.

Adult↗

Comparison of mRAST and CAP with skin end point titration for Alternaria tenuis and dermatophagoides pteronyssinus.

There has been a recent explosion of new in vitro tests for the diagnosis of allergies. At present there is no general agreement on which type of in vitro test is best. Recently our hospital switched in vitro testing from the modified radioallergosorbent system (mRAST) to the Pharmacia CAP system (CAP). While changing in vitro testing techniques, 47 patients were tested with both the mRAST and CAP tests. Comparisons were made between the mRAST and CAP results of Alternaria tenuis and Dermatophagoides pteronyssinus allergens. These results were then compared with the results of patients who also underwent intradermal skin testing based on end point titration techniques.

Allergens↗

Efficacy of immunotherapy based on skin end-point titration.

OBJECTIVE: The purpose of this study is to examine the efficacy of skin end-point titration (SET) as a method of assessing skin responsiveness, selecting antigens, and initiating treatment for successful inhalant immunotherapy. STUDY DESIGN: This study is a prospective, randomized, controlled, double-blind investigation. Eighteen patients were randomly assigned to 1 of 2 groups: an experimental group treated for all positive antigens, and a control group treated for all positive antigens, with the exception of the study antigens. Quality of life was assessed with 3 dependent measures, and response to nasal challenge and nasal endoscopic evaluations were conducted. Ten patients completed the 6-month study. RESULTS: There were significant improvements in the emotional component of sinus-related disability, in response to nasal challenge, and in the endoscopic appearance of the mucosa, regardless of patient group. There was a trend toward improved quality of life among experimental subjects. CONCLUSIONS: SET-based immunotherapy reduces self-rated disability over time. In addition, SET-based immunotherapy allows decrease in nasal reactivity and normalizes the endoscopic appearance of the nose.

Adult↗

Nurse-led titration models of care for heart failure reduced ejection fraction: a systematic narrative review of characteristics, patient outcomes, and healthcare resource utilization.

AIMS: Nurse-led titration (NLT) models of care assist with delivery of guideline directed medical therapy for patients with heart failure with reduced ejection fraction (HFrEF). Effectiveness of NLT is established but there is limited information of characteristics of models, patient outcomes and healthcare resource utilization. To build upon the existing evidence by providing a systematic narrative review of the literature of NLT of medications for patients with HFrEF. This review syntheses characteristics of NLT models of care, patient outcomes and healthcare resource utilization. METHODS AND RESULTS: A systematic narrative literature review with systematic search strategy, identification of results, thematic analysis and narrative synthesis. A search was conducted from 2012 to 2025 in Medline, Cinahl complete, Embase and Cochrane. Sixteen studies of NLT models of care were identified from 1944 screened records. Characteristics of models of care were participation of nurses, multidisciplinary teams, follow-up and common features of service delivery. Patient outcomes of mortality were favourable for those that received NLT. There is some evidence of changes in healthcare resource utilization; studies in which the NLT groups received more HF nurse visits and greater HF medication use also reported reduced rehospitalizations. CONCLUSION: Findings reinforce the published benefits of NLT. Additional studies examining adverse events and quality-of-life outcomes are needed to strengthen the evidence base. Several studies suggest a shift in resource use with NLT, highlighting the need for an economic evaluation to inform a cost-effective model of care.

Humans↗

Skin endpoint titration. Still the standard?

Skin endpoint titration, being both quantitative and calibrated in accordance with the patient's own reactivity, may still be considered the most sophisticated means of identifying an allergenic offender. Other forms of skin testing, simpler to perform, are rapidly becoming more uniform and quantitative. Laboratory tests provide more specific information and improved convenience. All occupy important positions in allergy diagnosis.

History, 20th Century↗

Blending skin endpoint titration and in vitro methods in clinical practice.

The definitive diagnosis of allergy involves proving the presence of allergen-specific IgE. This had traditionally been done by skin testing, the most precise method being skin endpoint titration. In vitro diagnostic methods offer advantages over skin tests and have become increasingly popular with both patients and physicians. However, thorough knowledge of skin testing techniques and interpretation of results is necessary for the physician using in vitro test methods and also allows moving back and forth between the two modalities in the preparation of antigen treatment sets and adjustment of immunotherapy dosage.

Antibody Specificity↗

The rapidity of drug dose escalation influences blood pressure response and adverse effects burden in patients with hypertension: the Quinapril Titration Interval Management Evaluation (ATIME) Study. ATIME Research Group.

BACKGROUND: Antihypertensive medication doses are typically increased within several weeks after initiation of therapy because of inadequate blood pressure (BP) control and/or adverse effects. METHODS: We conducted a parallel-group clinical trial with 2935 subjects (53% women, n=1547) aged 21 to 75 years, with Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VI stages 1 to 2 hypertension, recruited from 365 physician practices in the southeastern United States. Participants were randomized either to a fast (every 2 weeks; n=1727) or slow (every 6 weeks; n=1208) drug titration. Therapy with quinapril, an angiotensin-converting enzyme inhibitor, was initiated at 20 mg once daily. The dose was doubled at the next 2 clinic visits until the BP was lower than 140/90 mm Hg or a dose of 80 mg was reached. RESULTS: Pretreatment BP averaged 152/95 mm Hg. Patients with stage 2 hypertension reported more symptoms than those with stage 1. The BP averaged 140/86, 137/84, and 134/83 mm Hg in the slow group compared with 141/88, 137/85, and 135/84 mm Hg in the fast group at the 3 respective clinic visits. The BP control rates to lower than 140/90 mm Hg at the 3 clinic visits were (slow, fast, respectively) 41.3%, 35.7% (P<.001); 54.3%, 51.5% (P=.16); and 68%, 62.3% (P=.02). In the fast group, 10.7% of participants experienced adverse events vs 10.8% in the slow group; however, 21.0% of adverse events in the fast group were "serious" vs only 12% in the slow group. CONCLUSION: Slower dose escalation of the angiotensin-converting enzyme inhibitor quinapril provides higher BP control rates and fewer serious adverse events than more rapid drug dose escalation.

Adult↗

Titration of recombinant woodchuck hepatitis virus DNA in adult woodchucks.

In vivo transfection of Eastern woodchucks (Marmota monax) with recombinant woodchuck hepatitis virus (WHV) DNA is effective in inducing virus infection for the study of replication, pathogenicity, and oncogenicity of wild-type and mutated WHV. The one drawback to this procedure is the need for preparation of large amounts of WHV DNA. Reduction of the amount of WHV DNA in the transfection protocol necessary to induce infection would save considerable time and resources. Therefore, we conducted a titration of WHV DNA, ranging from 50 micrograms to 50 pg of DNA, in adult woodchucks to determine the minimum infectious dose of recombinant WHV DNA. As little as 50 ng of transfected WHV DNA induced productive infection in adult woodchucks. Thus, transfection with large amounts of recombinant WHV DNA appears to be unnecessary.

Animals↗

Dose titration of nebulized budesonide in young children.

We compared the clinical effect of the glucocorticoid budesonide delivered from two nebulizers Aiolos and Pari LL in 38 children less than 4 years of age (mean age, 20.2 months) with chronic wheeze. The design was a controlled, single-blind, randomized, cross-over, dose titration study. After a 1-week run-in, patients were randomized to treatment with 1 mg budesonide b.i.d. for 2 weeks from either an Aiolos or a Pari LL nebulizer. This was followed by a gradual dose reduction period during which the budesonide dose was reduced at 2-week intervals until unacceptable asthma symptoms appeared or the placebo level was reached. The patient was then switched to budesonide 1 mg b.i.d. from the other nebulizer for 2 weeks, after which the dose was reduced at 2-week intervals as described for the first period. Patients who completed the study on placebo for 2 weeks without deterioration of their asthma were not included in the statistical analysis. During Period #1 the minimum effective dose of budesonide was 2 mg/day in 9 patients, 1 mg/day in 10 patients, and 0.5 mg/day in 13 patients. In Period #2 the corresponding figures were 14, 5, and 13 patients. Six patients were excluded after the first period because their asthma control did not deteriorate during dose reduction and when finishing on placebo for 2 weeks. For both nebulizers the reduction in budesonide dose was associated with a small increase in symptoms and use of rescue terbutaline. The mean dose of budesonide delivered to the patient by the Aiolos was twice as large as that delivered by the Pari LL: 26% vs. 13% of the nominal dose assessed by the filter method. Nevertheless, no statistically significant difference in clinical effect or mean minimal effective dose (1.1 mg for Aiolos and 1.2 mg for Pari LL) could be detected between the two nebulizers. No serious adverse events were observed. We conclude that the minimal effective dose of nebulized budesonide varies from 0.5 to 2.0 mg/day in young children with asthma. A higher drug delivery, as assessed by the filter method, does not necessarily result in better clinical control or lower minimal effective dose. Further studies are needed to assess whether this is due to insufficient sensitivity of the study design in detecting a difference in clinical effect, or whether measurements of drug delivery by the filter method do not reflect lung deposition or clinical effect in young children with wheezing.

Asthma↗

Determination of protein binding of troglitazone stereoisomers by fluorometric titration.

Determination of the protein binding of troglitazone is difficult because of its high adsorption to filters and membranes and the instability of the stereoisomers. We attempted to assess the protein binding of four stereoisomers of troglitazone in the plasma and albumin from several species by the method using fluorescent probes. The inhibition constants (Ki) for the stereoisomers of troglitazone were obtained from the decreases in fluorescence intensity of dansylsarcosine caused by competitive inhibition. Each stereoisomer of troglitazone displaced dansylsarcosine, a typical specific fluorescent probe for the diazepam binding site on human serum albumin (HSA). The highest binding affinity for dansylsarcosine was observed with HSA (dissociation constant, Kd,1 = 0.5 microM), while it was lowest in the mouse (Kd,1 = 18 microM). The Ki values for KK and ddY mouse plasma and mouse and rat albumin were in the range 2-15 microM, and there were no large variations among stereoisomers, the maximum differences being twofold. For human plasma and albumin, the displacement could not be accounted for by a simple competitive inhibition. Comparison between unbound fraction (fu) values calculated from thus obtained Ki values and those of a mixture of the four stereoisomers determined by high-performance frontal analysis showed that the fu values obtained by fluorometric titration were higher, while the relative differences among the stereoisomers in terms of animal species and strain were comparable for the two methods. Small differences in protein binding among stereoisomers of troglitazone may not be the major reason for their stereoselective pharmacokinetics.

Animals↗

Isothermal titration calorimetry and differential scanning calorimetry as complementary tools to investigate the energetics of biomolecular recognition.

The principles of isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) are reviewed together with the basic thermodynamic formalism on which the two techniques are based. Although ITC is particularly suitable to follow the energetics of an association reaction between biomolecules, the combination of ITC and DSC provides a more comprehensive description of the thermodynamics of an associating system. The reason is that the parameters DeltaG, DeltaH, DeltaS, and DeltaCp obtained from ITC are global properties of the system under study. They may be composed to varying degrees of contributions from the binding reaction proper, from conformational changes of the component molecules during association, and from changes in molecule/solvent interactions and in the state of protonation.

Animals↗

Low-tech electrophoresis, small but beautiful, and effective: electrophoretic titration curves of proteins.

Migration across a stationary pH gradient results in the electrophoretic titration of a protein's dissociable groups. From the resulting curves, some properties of the protein may be derived, including overall amino acid composition and type of mutation between polymorphic variants, as well as range of stability or, for enzymes, of catalytic activity. Analysis with this technique is a stringent purity criterion; other applications allow the study of interacting systems and the planning of chromatographic fractionations based on differences in surface charge.

Amino Acids↗

Evaluation of the performance of immobilized penicillin G acylase using active-site titration.

Penicillin G acylase from Escherichia coli was immobilized on Eupergit C with different enzyme loading. The activity of the immobilized preparations was assayed in the hydrolysis of penicillin G and was found to be much lower than would be expected on the basis of the residual enzyme activity in the immobilization supernatant. Active-site titration demonstrated that the immobilized enzyme molecules on average had turnover rates much lower than that of the dissolved enzyme. This was attributed to diffusion limitations of substrate and product inhibition. Indeed, when the immobilized preparations were crushed, the activity increased from 587 U g-1 to up to 974 U g-1. The immobilized preparations exhibited up to 15% lower turnover rates than the dissolved enzyme in cephalexin synthesis from 7-ADCA and D-(-)-phenylglycine amide. The synthesis over hydrolysis ratios of the immobilized preparations were also much lower than that of the dissolved enzyme. This was partly due to diffusion limitations but also to an intrinsic property of the immobilized enzyme because the synthesis over hydrolysis ratio of the crushed preparations was much lower than that of the dissolved enzyme.

Antigens, Neoplasm↗

Development of a novel titration and off-gas analysis (TOGA) sensor for study of biological processes in wastewater treatment systems.

The development of the new TOGA (titration and off-gas analysis) sensor for the detailed study of biological processes in wastewater treatment systems is outlined. The main innovation of the sensor is the amalgamation of titrimetric and off-gas measurement techniques. The resulting measured signals are: hydrogen ion production rate (HPR), oxygen transfer rate (OTR), nitrogen transfer rate (NTR), and carbon dioxide transfer rate (CTR). While OTR and NTR are applicable to aerobic and anoxic conditions, respectively, HPR and CTR are useful signals under all of the conditions found in biological wastewater treatment systems, namely, aerobic, anoxic and anaerobic. The sensor is therefore a powerful tool for studying the key biological processes under all these conditions. A major benefit from the integration of the titrimetric and off-gas analysis methods is that the acid/base buffering systems, in particular the bicarbonate system, are properly accounted for. Experimental data resulting from the TOGA sensor in aerobic, anoxic, and anaerobic conditions demonstrates the strength of the new sensor. In the aerobic environment, carbon oxidation (using acetate as an example carbon source) and nitrification are studied. Both the carbon and ammonia removal rates measured by the sensor compare very well with those obtained from off-line chemical analysis. Further, the aerobic acetate removal process is examined at a fundamental level using the metabolic pathway and stoichiometry established in the literature, whereby the rate of formation of storage products is identified. Under anoxic conditions, the denitrification process is monitored and, again, the measured rate of nitrogen gas transfer (NTR) matches well with the removal of the oxidised nitrogen compounds (measured chemically). In the anaerobic environment, the enhanced biological phosphorus process was investigated. In this case, the measured sensor signals (HPR and CTR) resulting from acetate uptake were used to determine the ratio of the rates of carbon dioxide production by competing groups of microorganisms, which consequently is a measure of the activity of these organisms. The sensor involves the use of expensive equipment such as a mass spectrometer and requires special gases to operate, thus incurring significant capital and operational costs. This makes the sensor more an advanced laboratory tool than an on-line sensor.

Bacteria, Aerobic↗

Production of fuculose-1-phosphate aldolase using operator-repressor titration for plasmid maintenance in high cell density Escherichia coli fermentations.

We report a novel application for the operator-repressor titration (ORT) plasmid maintenance system. The ability of ORT to maintain a plasmid during production of DNA has been demonstrated previously. In this study, we have used the ORT system to maintain a plasmid during high cell density cultivation and expression of a recombinant protein. No evidence of plasmid loss was seen during protein expression at high cell densities. In addition, the quantity of protein produced using this system was similar to traditional plasmid maintenance systems.

Aldehyde-Lyases↗

Rapid titration with intravenous morphine for severe cancer pain and immediate oral conversion.

BACKGROUND: Cancer pain emergencies presenting with severe excruciating pain require a rapid application of powerful analgesic strategies. The aim of the current study was to evaluate a method of rapid titration with intravenous morphine to achieve relief of cancer pain of severe intensity. METHODS: Forty-nine consecutive patients admitted to a Pain Relief and Palliative Care Unit for severe and prolonged pain were enrolled in the study. Pain was evaluated on a numeric scale of 0-10 (0 indicated no pain and 10 indicated excruciating pain). After the initial assessment (T0), an intravenous line was inserted and boluses of morphine (2 mg every 2 minutes) were given until the initial signs of significant analgesia were detected or severe adverse effects occurred (T1). A continuous reassessment was warranted and the effective total dose administrated intravenously was assumed to last approximately 4 hours and was calculated for 24 hours. The dose immediately was converted to oral morphine (a 1:3 ratio for low doses and a 1:2 ratio for high doses). RESULTS: Data from 45 patients was analyzed. A significant decrease in pain intensity was achieved in a mean of 9.7 minutes (95% confidence interval [95% CI], 7.4-12.1 minutes), using a mean dose of intravenous morphine of 8.5 mg (95% CI, 6.5-10.5 mg). The doses administered rapidly were converted to oral morphine and pain control was maintained until the patient's discharge, which occurred in a mean of 4.6 days (95% CI, 4.1-5.2 days). The incidence of adverse effects was minimal. CONCLUSIONS: The results of the current study demonstrate that cancer pain emergencies can be treated rapidly in the majority of cancer patients with an acceptable level of adverse effects. Intravenous administration of morphine requires initial close supervision and continuity of medical and nursing care.

Administration, Oral↗