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At least 883 records · Page 49Linked to original sources
PubMed1995

Octreotide treatment of carcinoid syndrome: analysis of published dose-titration data.

BACKGROUND: Octreotide has proven therapeutically effective in carcinoid syndrome, but the rarity of carcinoid tumors has hampered detailed dose-ranging studies. This study analysed published dose-titration data on octreotide use in carcinoid patients to (a) investigate the relation between octreotide dose and efficacy and (b) establish octreotide dosing recommendations for maximum therapeutic benefit. METHOD: An exhaustive, computer-assisted literature search for published articles employing octreotide to manage patients with carcinoid syndrome was performed using several databases. The relation between octreotide dose and efficacy in decreasing urinary 5-hydroxyindoleacetic acid (5-HIAA) levels, flushing and diarrhoea was analysed for seven dose ranges by pooling data from selected articles. RESULTS: Analysis of data compiled from 62 published studies revealed that maximum effective therapeutic doses of octreotide effectively controlled symptoms in up to 93% of patients, and that increasing the dose of octreotide is associated with increased benefit with respect to control of flushing, diarrhoea and 5-HIAA levels. CONCLUSIONS: We recommend starting octreotide therapy at 100 micrograms subcutaneously t.d.s. in patients with mild/moderate, non-life-threatening carcinoid syndrome. Since therapeutic response to octreotide varies markedly among patients, we recommend titrating the octreotide dose in increments of 50-100 micrograms every 8 h until adequate symptom control is achieved.

Carcinoid Tumor↗
PubMed1998

Clinical usefulness of the bispectral index for titrating propofol target effect-site concentration.

The bispectral index, a new processed electroencephalographic parameter which may give information on depth of anaesthesia, was used in 58 patients undergoing outpatient gynaecological surgery in order to study if the addition of bispectral index monitoring to standard clinical monitoring could improve the titration of target propofol concentration when using effect-site target-controlled propofol infusion for sedation. In Group 1 (n = 30), the bispectral index was recorded but the anaesthetist was unaware of the readings and therefore only classical signs of depth of anaesthesia were used to guide the anaesthetist in controlling the effect-site concentration. In Group 2 (n = 28), bispectral index readings were available to the anaesthetist and effect-site concentration was adjusted to ensure that bispectral index was maintained between 40 and 60. Similar propofol induction and maintenance doses, blood and effect-site concentrations and mean bispectral index were found in the two groups. A greater percentage of bispectral index readings lying outside the target range (i.e. < 40 or > 60) and more movement at incision and during maintenance were found in Group 1. There was a trend towards more implicit awareness in patients in Group 1. Bispectral index was found to be useful for measuring depth of sedation when using propofol target-controlled infusion. Propofol dosage could not be decreased but a more consistent level of sedation could be maintained due to a more satisfactory titration of target effect-site concentration.

Adolescent↗
PubMed1978

In vivo tests with pollen extracts previously investigated by means of direct RAST titration allergen assay.

The allergenic potency of different birch, Timothy and mugwort pollen extracts was determined by means of a direct RAST titration allergen assay. For birch and Timothy allergens, the results of skin and provocation tests did not confirm the results of the in vitro determinations of allergenicity. There was a poor correlation between the results of skin tests and the results of Phadebas RAST for determination of specific IgE to mugwort, whereas the correlation between skin tests and RAST for other allergens was excellent. It is concluded that direct RAST titration allergen assay is not adequate for all kinds of allergen preparations and that the Phadebas RAST for mugwort is less sensitive than the RAST for other allergens. The diagnostic efficacy of the different allergen preparations could not be evaluated.

Allergens↗
PubMed1995

Long-term titrated recombinant interferon-alpha 2a in chronic hepatitis C: a randomized controlled trial.

The efficacy and tolerability of 12-month treatment with titrated doses of recombinant interferon-alpha 2a (IFN-alpha 2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN-alpha 2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response (n = 35), or to no therapy (n = 32; controls). End-of-treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls (P < 0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) (P = 0.031). Follow-up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls (P < 0.001). The eight sustained responders and 27 non-responders or relapsers received similar mean total doses of IFN (565 MU vs 545 MU) and had a similar incidence of anti-IFN neutralizing antibodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long-term clearance of HCV RNA and normal ALT levels in 23% of patients.

Adolescent↗
PubMed2004

Improving lipid management--to titrate, combine or switch.

Despite the benefits of statin therapy, cholesterol management remains suboptimal and many patients do not achieve their recommended low-density lipoprotein cholesterol (LDL-C) goals. The use of insufficient doses, limited drug effectiveness and poor patient compliance may contribute to the treatment gap. Options for improving lipid management include dose titration, combination therapy or prescribing a more efficacious statin. LDL-C reductions are generally modest when patients' current statin dose is titrated, and there may be an increased potential for adverse effects. Combining statin therapy with another lipid-modifying agent can provide additional LDL-C reductions, but cost, tolerability and compliance should be considered. In general, switching to a more efficacious statin is a cost-effective way of enabling more patients to achieve recommended targets without increasing dosages. When considering the options available, physicians should balance efficacy, cost and safety to enable more patients to attain LDL-C goals and achieve greater therapeutic gain from statin treatment.

Cholesterol, LDL↗
PubMed1985

Diagnosis and immunotherapy of mould allergy. II. Reproducibility and relationship between skin sensitivity estimated by end-point titration and histamine equivalent reaction using skin prick test and intradermal test.

To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1975

Spectrophotometric titration of tyrosyl residues in alkaline mesentericopeptidase.

At pH 7.0 the alkaline mesentericopeptidase has ultraviolet absorption spectrum with a minimum at 251 nm and a maximum at 280 nm and no visible absorption. From the tyrosine to tryptophan ratio a value of 3 tryptophyl residues per mole of protein is obtained. The molar extinction coefficient at 280 nm is 3.55 X 10(4)M-1cm-1. Spectrophotometric titration studies show that the molecule of mesentericopeptidase contains seven phenolic groups with a pKapp - 9.92 and four to five groups with a pKapp = 11.96. Denaturing agents, such as 5 M guanidine hydrochloride or alkali, normalize the ionization of the tyrosyl residues. There is a good correlation between the spectrophotometric titration data and the results for the reactivities of the tyrosines in mesentericopeptidase towards tetranitromethane. The correlation is explained by the mechanism of nitration. Conclusions about the state of the tyrosyl residues and the three-dimensional structure of mesentericopeptidase are made.

Bacillus↗
PubMed1977

Studies on groundnut proteins. VI. Isolation, characterisation and hydrogen ion titration of conarachin II.

A method is described for isolating conarachin II in a homogeneous form by the techniques of DEAE-cellulose chromatography, polyacrylamide gel electrophoresis and sedimentation velocity. The protein contains 0.72% carbohydrate and no phosphate. Hydrogen ion titration curve indicated that the sidechain carboxyl, imidazol and epsilon-amino groups titrated with normal pK Int values and their number agreed with the analytical values obtained from amino acid analysis. However, tyrosine phenolic groups had abnormal pK Int of 10.5.

Amino Acids↗
PubMed1979

Hydrogen-tritium exchange titration of the histidine residues in bovine heart cytochrome c and analysis of their microenvironment.

Microenvironments of the three histidine residues located at the positions 18, 26, and 33 from the amino terminus in bovine heart cytochrome c were analysed in solution by the hydrogen-tritium exchange titration method, which has been developed in this laboratory. Histidine-18, which is liganded to the heme iron, and histidine-26 did not incorporate tritium in native state, indicating that the two are located in solvent inaccessible hydrophobic regions. Histidine-33 was labeled with tritium to an appreciable extent and seemed to be partially buried in the molecule. The pKa value estimated for histidine-33 was 6.1 at 37 degrees by the tritium exchange titration, suggesting that the residue interacts very weakly with a neighboring cationic group. These results seem to be compatible with the tertiary structure of the protein deduced from the X-ray crystallographic analysis.

Amino Acid Sequence↗
PubMed2005

A-line autoregression index monitoring to titrate inhalational anaesthesia: effects on sevoflurane consumption, emergence time and memory.

BACKGROUND: A-line autoregression index (AAI) is a parameter derived from auditory evoked potentials proposed as depth of anaesthesia monitor. We evaluated the effects of AAI guidance on sevoflurane consumption, emergence time, explicit and implicit memory. METHODS: One hundred patients submitted to major abdominal surgery were randomized into two groups. In group A (n = 50), sevoflurane was titrated according to AAI (target = 20 +/- 5), in group B (n = 50) according to clinical signs. Anaesthesia was induced with fentanyl, propofol, atracurium and maintained with sevoflurane. The mean value of sevoflurane consumption (g/min) and emergence time has been assessed in both groups. After emergence, A test of explicit memory was administered. We assessed implicit memory using a category generation test. RESULTS: In group A, mean sevoflurane consumption was significantly (P = 0.0001) reduced by 20.4% and mean emergence time was significantly (P = 0.00012) shorter by 2 min with respect to group B. No patients experienced explicit memory while the difference between the two groups in implicit memory results was not significant (P = 0107). CONCLUSIONS: AAI titration of anaesthesia allows a significant reduction in sevoflurane consumption and emergence time without significant effects on the incidence of explicit and implicit memory. Nevertheless the relationship between AAI and memory requires studies in larger groups of patients.

Abdomen↗
PubMed1977

Ionization behaviour of native apolipoproteins and of their complexes with lecithin. 1. Calorimetric and potentiometric titration of the native apoA-I protein and of the apoA-I protein-dimyristoyl lecithin complex.

The ionization behaviour of native apoA-I protein is compare to that of its complex with synthetic dimyristoyl lecithin in studies using calorimetric, potentiometric and spectrophotometric titration. In the presence of phospholipids, 10 out of 21 lysines together with 22 acidic residues are masked in the complex. All tyrosines remain accessible to titration below pH 13. The apparent ionization enthalpy of the 11 lysine residues is not affected by the presence of phospholipids. These data are consistent with discrete binding sites located in the apoprotein helical segments as suggested by the model of Segrest et al. [FEBS Lett. 38, 247-253 (1974)]. A tentative localisation of lysine, arginine, aspartic acid and glutamic acid residues directly involved in phospholipid binding is suggested, assuming that such helical regions are involved in apoprotein-phospholipid association.

Amino Acid Sequence↗
PubMed1980

Direct enzyme titration curve of NADH: cytochrome b5 reductase by combined isoelectric focusing/electrophoresis. Interactions between enzyme and cytochrome b5.

Methemoglobin reduction in human red cells involves successively an electron transport from NADH to a soluble form of cytochrome b5 (step 1) and from cytochrome b5 to methemoglobin (step 2). Step 1 is catalysed by an enzyme, soluble NADH:cytochrome b5 reductase (EC 1.6.2.2). Step 2 is non-enzymatic and involves complementary electrostatic interactions between acidic residues of cytochrome b5 and basic residues of hemoglobin [Gacon et al. (1980) Proc. Natl Acad. Sci. USA, 77, 1917-1921]. Here we present data indicating a similar mode of interactions occurring in step 1 between cytochrome b5 reductase and cytochrome b5. These results have been obtained by using the combined isoelectric focusing/electrophoresis method [Righetti et al. (1978) J. Chromatogr. 166, 455-460] allowing a direct titration of both entities either separately or in a mixture. This is the first report on the obtention of a direct titration curve of an enzyme visualized after specific staining (zymogram). The pH dependence of the Michaelis constant for cytochrome b5 is also in agreement with the hypothesis that electrostatic charges, which are maximal below pH 7.0, are essential in the interaction between cytochrome b5 and its reductase.

Animals↗
PubMed1983

Binding of 4-methylumbelliferyl beta-D-galactosyl-(1 leads to 3)-N-acetyl-beta-D-galactosaminide to peanut agglutinin. Characterisation and application in substitution titrations.

Binding of 4-methylumbelliferyl-2-acetamido-2-deoxy-3-O-(beta-D-galactopyranosyl) beta-D-galactopyranoside [MeUmb beta Gal(beta 1 leads to 3)GalNAc] to peanut agglutinin was characterized by equilibrium dialysis and by measurement of the increase in ultraviolet absorption or fluorescence of the chromophoric glycoside upon continuous titration with excess of the lectin. All data in the 4-30 degrees C range correspond to delta G = -(26.5 +/- 0.1) kJ mol-1, delta H = -(58.4 +/- 2) kJ mol-1 and delta S = -(107 +/- 8)J mol-1 K-1. Values of the association constants are e.g. K = 2.5 X 10(5) M-1 at 4 degrees C and K = 4.5 X 10(4) M-1 at 25 degrees C. MeUmb beta Gal(beta 1 leads to 3)GalNAc was used as an indicator ligand to determine K values for nonchromophoric carbohydrates by continuous displacement titrations, measuring either fluorescence or difference in absorption of the indicator. The data were analyzed in terms of the general expression for a non-ideal indicator system (as detailed in the appendix). Thus, the values of K are not underestimated. They are K = 4.8 X 10(3) M-1 for methyl alpha-D-galactopyranoside [Me alpha Gal], 2.0 X 10(3) M-1 for methyl beta-D-galactopyranoside [Me beta Gal] and 4.7 X 10(3) M-1 for lactose [Gal(beta 1 leads to 4)Glc], all at 14.5 degrees C. The MeUmb difference absorption spectra resulting from binding of the lectin with MeUmb beta Gal(beta 1 leads to 3)GalNAc and MeUmb beta Gal(beta 1 leads to 4)Glc are larger than for MeUmb beta Gal and MeUmb alpha Gal. These observations are consistent with the extended nature of the combining site of peanut agglutinin.

Arachis↗
PubMed1986

Active-site titration of enzymes at high concentration. Application to myosin ATPase.

The number of active sites of soluble and filamentous myosin and of its subfragments, heavy meromyosin and subfragment-1, has been determined. The titration involves steady-state kinetic measurements at a high enzyme concentration and varying substrate concentrations (or vice versa), in the presence of a substrate-regenerating system. Some practical and theoretical conditions for its execution are given, and, in particular, the effect of a possible heterogeneity of the active sites on the titration curves is analysed. Under the experimental conditions of the study, the number of active sites is close to that of myosin heads, and the heads seem to be functionally identical; the catalytic constants kcat and Km characterizing each active site are similar within some limits (1-2 for the ratio of kcat values; 1-5 for that of Km values).

Adenosine Triphosphatases↗
PubMed1991

Analysis of inhibitor binding to the mitochondrial cytochrome c reductase by fluorescence quench titration. Evidence for a 'catalytic switch' at the Qo center.

The binding characteristics of inhibitors of the mitochondrial cytochrome c reductase were studied by fluorescence quench titration. Based on the standard binding equation, the applied numerical method allowed the online recorded titration curves to be interpreted by fitting the Kd, the number of binding sites, and the specific fluorescence of the free and the bound inhibitor. For the Qi center, 2-n-nonyl-4-hydroxyquinoline N-oxide and for the Qo center (E)-beta-methoxyacrylate-stilbene (MOA-stilbene) were used as fluorescing inhibitors. The experiments could be extended to other, non-fluorescing inhibitors by competition analysis. Using this method we were able to compare the binding behaviour of Qi and Qo center inhibitors under different redox states of the enzyme using the same experimental set up. We studied the competition between inhibitors of the cytochrome c reductase representative for all subgroups and demonstrated that at least three inhibitor binding sites exist, two located in the Qo center, one located in the Qi center. Determination of the dissociation constants of the oxidized, the partially reduced and the fully reduced enzyme showed that inhibitor binding at the Qi center is not redox-dependent. In contrast, the binding of MOA-stilbene to the Qo center is decreased after reduction of the iron-sulfur center and cytochrome c1, whereas this redox change increases the affinity for a Qo center inhibitor of the hydroxynaphthoquinone type, 3-n-undecyl-2-hydroxynaphthoquinone. From these results, aware of the fact that the inhibitory mechanism at the Qo center is a non-competitive one, we made the hypothesis of a 'catalytic switch' to explain both the bifurcation of electron flow and the inhibition at the Qo center. A steric blockage of one of two conformational states could serve as a cogent explanation for the great structural variability of the inhibitors and differential effects on the redox centers exerted by the inhibitors. Moreover, the proposed 'switch' gives some insight into other experimental results which are difficult to explain with the ubiquinone cycle as currently formulated.

Acrylates↗
PubMed1991

Uterine activity in dysfunctional labour and target uterine activity to be aimed with oxytocin titration.

Uterine activity was quantified using a transducer tipped intrauterine catheter in 75 nulliparous women with dysfunctional labour. The active contraction area profiles in these women were below the median levels reported for those who had normal progress of labour from our institution. When uterine activity was augmented with oxytocin, 90.7% progressed in labour and delivered vaginally. Six patients (8%) showed poor progress despite good uterine activity and had to be delivered by caesarean section (CS) for failure to progress and signs of cephalopelvic disproportion. The pre- and post-augmentation uterine activity were similar in those who delivered vaginally or by CS and was not helpful in identifying those who had cephalopelvic disproportion. Of the 75 women who had slow progress of labour, 50 had a contraction frequency of less than 1 in 3 min whilst 25 had a minimum frequency of 1 in 3 min or more. All except one in the latter group delivered vaginally when oxytocin was titrated to achieve a contraction frequency of 1 in 2 to 2 1/2 min which were clinically judged to be adequate based on a duration greater than 40 sec. Oxytocin should be titrated to achieve a target contraction frequency of 1 in 2 to 2 1/2 min lasting greater than 40 sec to achieve good obstetric outcome in those with dysfunctional labour.

Adult↗
PubMed2001

Titrated oral misoprostol solution for induction of labour: a multi-centre, randomised trial.

OBJECTIVES: To determine the effects of titrated oral misoprostol solution, compared with vaginal dinoprostone. STUDY DESIGN: Open, randomised clinical trial. SETTING: Academic hospitals in South Africa and Liverpool, UK. METHODS: Women undergoing induction of labour after 34 weeks of pregnancy were allocated by randomised, sealed opaque envelopes, to induction of labour with titrated oral misoprostol solution, or two doses of vaginal dinoprostone (2mg) administered six hours apart. Failure to deliver within 24 hours of randomisation was the primary outcome on which the sample size was based. The data were analysed by intention-to-treat. RESULTS: Six hundred and ninety-five women were randomly allocated: 346 to oral misoprostol and 349 to vaginal dinoprostone. There were no significant differences in substantive outcomes. Vaginal delivery within 24 hours was not achieved in 38% of women in the oral misoprostol group and 36% in the vaginal dinoprostone group (RR 1.08; 95% CI 0.89-1.31). The caesarean section rates were 16% and 20%, respectively (RR 0.80; 95% CI 0.58-1.11). Hyperstimulation with fetal heart rate changes occurred in 4% of women in the oral misoprostol group and 3% after vaginal dinoprostone (RR 1.32, 95% CI 0.59-2.98). The response to induction of labour in women with unfavourable cervices was somewhat slower with misoprostol when membranes were intact, and with dinoprostone when membranes were ruptured. There were no differences in neonatal outcome between the two groups. CONCLUSIONS: This new approach to oral misoprostol administration was successful in minimising the risk of uterine hyperstimulation, which has been a feature of misoprostol use for induction of labour, at the expense of a somewhat slower response in women with intact membranes and unfavourable cervices. Misoprostol is not registered for use in pregnant women, and further research is needed to confirm optimal and safe dosages.

Administration, Intravaginal↗
PubMed2004

Antihypertensive efficacy of candesartan-lisinopril in combination vs. up-titration of lisinopril: the AMAZE trials.

The AMAZE (A Multicenter Trial Using Atacand and Zestril vs. Zestril to Evaluate the Effects on Lowering Blood Pressure) program included two identical studies sponsored by AstraZeneca LP. The oral form of candesartan is candesartan cilexetil; for simplicity, the term "candesartan" is used throughout this manuscript. Two identical multicenter, randomized, double-blind studies were performed to determine if addition of the angiotensin receptor blocker candesartan was more effective in lowering blood pressure than up-titration of lisinopril. Hypertensive patients (N=1,096) who were uncontrolled on lisinopril 20 mg daily were randomized (1:1) to receive either 8 weeks of high-dose lisinopril (40 mg) or the addition of candesartan (16 mg) for 2 weeks followed by 32 mg for 6 weeks. Study 1 (n=538) demonstrated decreases in trough sitting systolic/diastolic blood pressures at Week 8 by 6.2/5.9 mm Hg, respectively, for the lisinopril up-titration treatment group and by 11.6/8.3 mm Hg, respectively, for the lisinopril plus candesartan treatment group (p<0.01 in comparing both blood pressures reductions between the two treatment groups). Corresponding results for Study 2 (n=558) are reductions of 8.7/6.2 mm Hg and 9.5/7.4 mm Hg, respectively, for each of the two treatment groups. For Study 2, comparisons of systolic/diastolic blood pressures between the two treatment groups were not statistically significantly different (p=0.51/p=0.08, respectively). Post hoc pooled analysis (N=1,096) demonstrated a slightly greater blood pressure reduction with lisinopril plus candesartan compared with lisinopril (3.1/1.7 mm Hg). A 95% confidence interval limit for the difference in least squares mean change from baseline in systolic blood pressure between the two treatment groups is -4.8 to -1.5 and is -2.8 to -0.7 in mm Hg for diastolic blood pressure. The blood pressure control rates (<140/<90 mm Hg) were 42.7% and 36.9%, respectively. Both treatment regimens were well tolerated in all groups. In conclusion, for hypertensive patients not controlled by lisinopril 20 mg once daily, addition of candesartan (32 mg once daily) or doubling the dose of lisinopril provides safe, additional reduction of blood pressure.

Aged↗