Good Clinical Response (good + clinical_response)

Distribution by Scientific Domains

Selected Abstracts

Co-administration of salbutamol and fluticasone for emergency treatment of children with moderate acute asthma,

Elizabeth Estrada-Reyes
This study aimed to compare the efficacy of nebulized therapy with salbutamol alone or in combination with fluticasone. In a randomized, double-blind clinical trial, 150 children with moderate acute asthma were randomly assigned to receive by nebulizations either (i) three doses of salbutamol 30 ,l/kg per dose, each dose administered every 15 min, (ii) three doses of salbutamol plus two doses of fluticasone 500 ,g/dose at 15 and 30 min after first dose of salbutamol, or (iii) three doses of salbutamol/fluticasone 500 ,g/dose, each combined dose administered every 15 min. Pulse oxymetry (SaO2), peak expiratory flow (PEF) and Wood et al. (Am J Dis Child, 123, 1972, 123) clinical scale were evaluated at baseline, 15, 30, 45, 60, 90 and 120 min after the first nebulization. Patients in the three groups significantly improved since 15 min after the first nebulization. We did not observe differences in the recovery of SaO2 and PEF among the three groups of treatment (p > 0.10). In group 3, children showed better clinical response at 120 min than the other two groups (p < 0.05). No significant adverse effects were observed with any treatment. To summarize, in children with acute moderate asthma, nebulized salbutamol at an accumulated dose of 90 ,l/kg plus fluticasone at an accumulated dose of 1500 ,g produced better clinical relief after 2 h. However, similar PEF and SaO2 responses were observed with salbutamol alone or in combination with different doses of fluticasone. [source]

Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation

Joseph E. Baggott
Objective To assess the catabolism of methotrexate (MTX) to 7-hydroxy-MTX (7-OH-MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism. Methods Urinary excretion of MTX and its catabolite, 7-OH-MTX, was measured in 2 24-hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7-OH-MTX concentrations were determined by high-performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7. Results Folic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7-OH-MTX, but folinic acid did not. Excretion of 7-OH-MTX (determined as a percentage of the dose of MTX or as mg 7-OH-MTX/gm creatinine) was not normally distributed (n = 39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7-OH-MTX excretion level (P < 0.05). Patients who received folic acid supplements had decreased 7-OH-MTX excretion (P = 0.03). Relatively high 7-OH-MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P < 0.05) (n = 35). Conclusion Our findings of a non-normal distribution of 7-OH-MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo. [source]

Development of a drug,disease simulation model for rituximab in follicular non-Hodgkin's lymphoma

David Ternant
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Serum concentrations of rituximab influence its clinical efficacy in follicular lymphoma (FL), but its concentration,effect relationship has not been described by pharmacokinetic,pharmacodynamic (PK,PD) modelling. , The genetic polymorphism of FCGR3A influences rituximab efficacy and its in vitro concentration,effect relationship. , Increasing rituximab dose and/or number of infusions may lead to a better clinical response in FL. WHAT THIS PAPER ADDS , This study is the first to describe the concentration,effect relationship of rituximab in populations of FL patients. , This PK,PD model relates progression-free survival with rituximab concentrations and takes into account the influence of FCGR3A polymorphism. , Clinical trials testing new dosing regimens of rituximab can be designed using this PK,PD model. AIM Rituximab has dramatically improved the survival of patients with non-Hodgkin's lymphomas (NHL), but the dosing regimen currently used should be optimized. However, the concentration,effect relationship of rituximab has never been described by pharmacokinetic,pharmacodynamic (PK,PD) modelling, precluding the simulation of new dosing regimens. The aim of this study was to develop a PK,PD model of rituximab in relapsed/resistant follicular NHL (FL). METHODS A model describing the relationship between rituximab concentrations and progression-free survival (PFS) was developed using data extracted from the pivotal study, which evaluated 151 relapsed/resistant FL patients. The influence of FCGR3A genetic polymorphism on the efficacy of rituximab was quantified using data from 87 relapsed/resistant FL patients. The predictive performance of the model was analysed using two independent datasets: a study that evaluated rituximab combined with chemotherapy [rituximab, cyclophosphamide, vincristine, adriamycin and prednisone (R-CHOP)] in 334 relapsed/resistant FL patients and a study that evaluated rituximab monotherapy in 47 asymptomatic FL patients with known FCGR3A genotype. RESULTS For R-CHOP, observed and model-predicted PFS (90% confidence interval) at 24 months were 0.50 and 0.48 (0.40, 0.56), respectively, for the observation arm, and 0.62 and 0.59 (0.50, 0.65), respectively, for the rituximab maintenance arm. For rituximab monotherapy, observed and predicted PFS at 24 months were 0.67 and 0.63, respectively, for FCGR3A -V/V patients, and 0.41 and 0.36 (0.25, 0.49), respectively, for FCGR3A -F carriers. CONCLUSIONS Our model provides a satisfactory prediction of PFS at 24 months. It can be used to simulate new dosing regimens of rituximab in populations of FL patients and should improve the design of future clinical trials. [source]

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided platinum-based 2-drug chemotherapy for unresectable nonsmall-cell lung cancer,

CANCER, Issue 9 2007
Yong Wha Moon MD
Abstract BACKGROUND. The study investigated correlations between adenosine triphosphate / chemotherapy response assay (ATP-CRA) and clinical outcomes after ATP-CRA-guided platinum-based chemotherapy for unresectable nonsmall-cell lung cancer (NSCLC). METHODS. The authors performed an in vitro chemosensitivity test, ATP-CRA, to evaluate the chemosensitivities of anticancer drugs such as cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and vinorelbine for chemonaive, unresectable NSCLC. The cell death rate was determined by measuring the intracellular ATP levels of drug-exposed cells compared with untreated controls. A sensitive drug was defined as a drug producing 30% or more reduction in ATP compared with untreated controls. Assay-guided platinum-based 2-drug chemotherapy was given to patients with pathologically confirmed NSCLC. RESULTS. Thirty-four patients were enrolled. Thirty tumor specimens were obtained by bronchoscopic biopsies and 4 obtained surgically. The median age was 61 years and 27 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0,1. The response rate was 43.8%. At a median follow-up period of 16.9 months, the median progression-free and overall survivals were 3.6 and 11.2 months, respectively. Patients were dichotomized into the platinum-sensitive (S; 20 patients) and resistant (R; 14 patients) groups. The positive/negative predictive values were 61.1% and 78.6% with a predictive accuracy of 68.8%. Although without significant differences in pretreatment parameters, the S-group showed better clinical response (P = .036), longer progression-free survival (P = .060), and longer overall survival (P = .025). CONCLUSIONS. Despite using bronchoscopic biopsied specimens, ATP-CRA and clinical outcomes correlated well after assay-guided platinum-based 2-drug chemotherapy for unresectable NSCLC. There was a favorable response and survival in the platinum-sensitive vs resistant groups. Cancer 2007. 2007 American Cancer Society. [source]

Mutations in the holocarboxylase synthetase gene HLCS,

HUMAN MUTATION, Issue 4 2005
Yoichi Suzuki
Abstract Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder. HLCS is an enzyme that catalyzes biotin incorporation into carboxylases and histones. Since the first report of the cDNA sequence, 30 mutations in the HLCS gene have been reported. Mutations occur throughout the entire coding region except exons 6 and 10. The types of mutations are one single amino acid deletion, five single nucleotide insertions/deletions, 22 missense mutations, and two nonsense mutations. The only intronic mutation identified thus far is c.1519+5G>A (also designated IVS10+5G>A), which causes a splice error. Several lines of evidence suggest that c.1519+5G>A is a founder mutation in Scandinavian patients. Prevalence of this mutation is about 10 times higher in the Faroe Islands than in the rest of the world. The mutations p.L237P and c.780delG are predominant only in Japanese patients. These are probably founder mutations in this population. Mutations p.R508W and p.V550M are identified in several ethic groups and accompanied with various haplotypes, suggesting that these are recurrent mutations. There is a good relationship between clinical biotin responsiveness and the residual activity of HLCS. A combination of a null mutation and a point mutation that shows less than a few percent of the normal activity results in neonatal onset. Patients who have mutant HLCS with higher residual activity develop symptom after the neonatal period and show a good clinical response to biotin therapy. Hum Mutat 26(4), 285,290, 2005. 2005 Wiley-Liss, Inc. [source]

Chromoblastomycosis: combined treatment with pulsed itraconazole therapy and liquid nitrogen cryotherapy

Ranthilaka R. Ranawaka MD
Background, Three patients with histology- and culture-proven chromoblastomycosis reported to the Colombo South Teaching Hospital, Sri Lanka, in 2005. All three were men (age range, 48,53 years). The duration of symptoms varied from 1 to 8 years and the lesions were on the lower limbs. Methods, The patients were treated simultaneously with liquid nitrogen cryotherapy and itraconazole pulses, i.e. 200 mg twice daily for 7 days per month, 1 week on and 3 weeks off. Cryotherapy was given every fortnight using large cotton swabs attached to ekels or the cryogun. Results, Two patients showed a good clinical response within 4 months, with negative histopathology and culture in 4,6 months. The third patient was very resistant to treatment and needed a step-up of the itraconazole dose. Conclusion, A combination of fortnightly liquid nitrogen cryotherapy and pulsed monthly itraconazole is cost-effective and shortens the duration of therapy compared with the use of itraconazole or cryotherapy alone. [source]

Gender Differences in Alcohol Treatment: An Analysis of Outcome From the COMBINE Study

ALCOHOLISM, Issue 10 2010
Shelly F. Greenfield
Background:, Relatively few studies have examined gender differences in the effectiveness of specific behavioral or pharmacologic treatment of alcohol dependence. The aim of this study is to assess whether there were gender differences in treatment outcomes for specific behavioral and medication treatments singly or in combination by conducting a secondary analysis of public access data from the national, multisite NIAAA-sponsored COMBINE study. Methods:, The COMBINE study investigated alcohol treatment among 8 groups of patients (378 women, 848 men) who received medical management (MM) with 16 weeks of placebo, naltrexone (100 mg/day), acamprosate (3 g/day), or their combination with or without a specialist-delivered combined behavioral intervention. We examined efficacy measures separately for men and women, followed by an overall analysis that included gender and its interaction with treatment condition in the analyses. These analyses were performed to confirm whether the findings reported in the parent trial were also relevant to women, and to more closely examine secondary outcome variables that were not analyzed previously for gender effects. Results:, Compared to men, women reported a later age of onset of alcohol dependence by approximately 3 years, were significantly less likely to have had previous alcohol treatment, and drank fewer drinks per drinking day. Otherwise, there were no baseline gender differences in drinking measures. Outcome analyses of 2 primary (percent days abstinent and time to first heavy drinking day) and 2 secondary (good clinical response and percent heavy drinking days) drinking measures yielded the same overall pattern in each gender as that observed in the parent COMBINE study report. That is, only the naltrexone by behavioral intervention interaction reached or approached significance in women as well as in men. There was a naltrexone main effect that was significant in both men and women in reduction in alcohol craving scores with naltrexone-treated subjects reporting lower craving than placebo-treated subjects. Conclusions:, This gender-focused analysis found that alcohol-dependent women responded to naltrexone with COMBINE's Medical Management, similar to the alcohol-dependent men, on a wide range of outcome measures. These results suggest that clinicians can feel comfortable prescribing naltrexone for alcohol dependence in both men and women. In this study, it is also notable that fewer women than men reported receiving any alcohol treatment prior to entry into the COMBINE study. Of note, women tend to go to primary health care more frequently than to specialty substance abuse programs for treatment, and so the benefit we confirm for women of the naltrexone and MM combination has practical implications for treating alcohol-dependent women. [source]

Use of Triple-Site Ventricular Pacing in a Patient with Severe Congestive Heart Failure and Atrial Fibrillation

Cardiac resynchronization therapy (CRT) has become an accepted treatment for selected patients with drug-resistant heart failure. Data for patients in atrial fibrillation (AF) remains limited but suggests benefit in these patients too. We report the case of an 82-year-old patient with heart failure, VVIR permanent pacemaker, and permanent AF who had an upgrade to triple-site CRT implantation with good clinical response. Triple-site ventricular pacing may enhance the chance of response and LV reverse remodeling and should be considered in AF patients undergoing CRT implantation. [source]

Favorable response of pediatric stem cell recipients to human protein C concentrate substitution for veno-occlusive disease

S. W. Eber
Abstract:, Plasminogen activator inhibitor 1 is known to be elevated in patients with hepatic VOD after intensive chemotherapy. To re-establish endogenous fibrinolysis and to inhibit thrombin formation, we used non-APC (zymogen) to normalize PAI-1 levels. As a consequence of thrombin formation inhibition and the consecutive inhibition of the coagulation cascade, this treatment is expected to reduce the elevated D-dimer level. Six pediatric stem cell recipients with moderate or severe VOD after busulfan or total body irradiation conditioning regimen are reported here who were therapy-refractory to defibrotide or rt-PA therapy. All patients had low levels of PC activity (16,39%). The administration of PC (60,240 IU/kg) led to a rapid and sustained rise in PC activity (target level >80%) with near normalization of prothrombin and partial thromboplastin time in all patients. Elevated PAI-1 levels declined. Five of the six patients showed a good clinical response with prompt resolution of clinical, sonographic, and laboratory signs of hepatic blood flow obstruction, while one patient with severe VOD, as well as concomitant liver GVHD and CMV disease, had a slow but detectable response to PC therapy. All patients survived. [source]

Granulomas in common variable immunodeficiency: A diagnostic dilemma

Karyn R Lun
SUMMARY A 60-year-old man with common variable immunodeficiency presented with a 7-year history of violaceous plaques and papules on the thighs, arms and trunk. In the preceding 2 years he had developed new lesions on both hands. He had been previously diagnosed with sarcoidosis on the basis of skin and visceral histology, but subsequent opinion was that these were sarcoid-like granulomas rather than being representative of true sarcoidosis. Biopsy of the hand lesions showed necrotizing granulomas, and a single acid-fast bacillus (AFB) was identified on Wade,Fite stain. Subsequent repeat tissue biopsies for histology, culture and polymerase chain reaction testing failed to confirm the presence of mycobacterial organisms and it was felt that the organism was a contaminant introduced during tissue processing. The hand lesions responded well to intralesional injections of triamcinolone acetonide 10 mg/mL and oral tetracycline 500 mg b.d. was later introduced with a good clinical response. The diagnostic dilemma of finding granulomatous inflammation in a patient with common variable immunodeficiency, and the significance of a single AFB on histology are discussed. The treatment of sarcoid-like granulomas with tetracycline therapy is also commented on. [source]