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Tolerable
Terms modified by Tolerable Selected AbstractsUnlocking the opportunity of tight glycaemic controlDIABETES OBESITY & METABOLISM, Issue 2005Inhaled insulin: clinical efficacy Numerous attempts have been made to develop novel routes of insulin delivery that are both effective and tolerable. Of all the potential non-invasive delivery options, pulmonary delivery is the most clinically viable. Early studies demonstrate that the inhaled insulin is rapidly absorbed and is closer to biological insulin than standard subcutaneous insulin (SC). To date, inhaled insulin (Exubera®) has been clinically assessed in more than 3500 patients with type 1 or type 2 diabetes, some treated for more than 7 years. Several phase 3 studies of 24-week duration have demonstrated comparable glycosylated haemoglobin (HbA1c) control in patients with type 1 diabetes treated with Exubera® vs. SC insulin. Similar results have also been recorded in patients with type 2 diabetes. Furthermore, Exubera® has shown clinical superiority to oral agent regimens in patients with type 2 diabetes who failed to achieve their target HbA1c using lifestyle modification and oral agents. Exubera® was well tolerated and treatment satisfaction was high, with Exubera® being the preferred insulin therapy in all studies. The results of these trials, and others, suggest that Exubera® may be a valuable tool to help a wide variety of patients with type 1 or type 2 diabetes reach their recommended goals for glycaemic control, irrespective of their current therapy. [source] Barrel Plating Rhodium Electrode: Application to Flow Injection Analysis of HydrazineELECTROANALYSIS, Issue 14 2005Jun-Wei Sue Abstract We introduce here the application of barrel plating technology for mass production of disposable-type electrodes. Easy for mass production, barrel plating rhodium electrode (Rh-BPE) is for the first time demonstrated for analytical application. Hydrazine was chosen as a model analyte to elucidate the electrocatalytic and analytical ability of the Rh-BPE system in pH,7 phosphate buffer solution. Flow injection analysis (FIA) of hydrazine showed a linear calibration range of 25,1000,ppb with a slope and a regression coefficient of 5,nA/ppb and 0.9946, respectively. Twenty-two replicate injections of 25,ppb hydrazine showed a relative standard deviation of 3.17% indicating a detection limit (S/N=3) of 2.5,ppb. The system can be continuously operated for 1 day without any alteration in the FIA signals and is tolerable to the interference of oxalic acid, gelatine, Triton X-100, and albumin for even up to 100 times excess in concentration with respect to 400,ppb hydrazine. Since the fabrication cost of the electrode is cheap, it is thus disposable in nature. Furthermore, barrel plating technique can be extendable to other transition metals for application in many fields of research interest. [source] Lenalidomide in combination with dexamethasone at first relapse in comparison with its use as later salvage therapy in relapsed or refractory multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2009Edward A. Stadtmauer Abstract This subset analysis of data from two phase III studies in patients with relapsed or refractory multiple myeloma (MM) evaluated the benefit of initiating lenalidomide plus dexamethasone at first relapse. Multivariate analysis showed that fewer prior therapies, along with ,2 -microglobulin (,2.5 mg/L), predicted a better time to progression (TTP; study end-point) with lenalidomide plus dexamethasone treatment. Patients with one prior therapy showed a significant improvement in benefit after first relapse compared with those who received two or more therapies. Patients with one prior therapy had significantly prolonged median TTP (17.1 vs. 10.6 months; P = 0.026) and progression-free survival (14.1 vs. 9.5 months, P = 0.047) compared with patients treated in later lines. Overall response rates were higher (66.9% vs. 56.8%, P = 0.06), and the complete response plus very good partial response rate was significantly higher in first relapse (39.8% vs. 27.7%, P = 0.025). Importantly, overall survival was significantly prolonged for patients treated with lenalidomide plus dexamethasone with one prior therapy, compared with patients treated later in salvage (median of 42.0 vs. 35.8 months, P = 0.041), with no differences in toxicity, dose reductions, or discontinuations despite longer treatment. Therefore, lenalidomide plus dexamethasone is both effective and tolerable for second-line MM therapy and the data suggest that the greatest benefit occurs with earlier use. [source] A randomized, double-blind, placebo-controlled clinical evaluation of a nicotine sublingual tablet in smoking cessationADDICTION, Issue 8 2000Mats Wallström Aims. Evaluation of the clinical efficacy and safety of a nicotine 2-mg sublingual tablet in smoking cessation. Design. A randomized, double-blind, placebo-controlled study of smokers using the 2-mg tablet for 3-6 months with follow-up to 12 months. Dosing was established according to baseline nicotine dependence, scored on the Fagerström Tolerance Questionnaire (FTQ): FTQ , 7, two tablets/hour (maximum 40/day); FTQ < 7, one tablet/hour (maximum 20/day). Setting. Smoking cessation programme in a department of oral and maxillofacial surgery. Participants. A total of 247 adult smokers, smoking , 10 cigarettes/day for , 3 years, of whom 123 received active and 124 placebo treatment. The study was powered to detect difference at 6 months. Measurements. Efficacy and safety were evaluated at 6 weeks and 3, 6 and 12 months. Self-reported abstinence was verified by exhaled CO < 10 p.p.m. Findings. Success rates for complete abstinence (no slips after 2 weeks) for active vs. placebo were 50% vs. 29% at 6 weeks, 42% vs. 23% at 3 months, 33% vs. 18% at 6 months and 23% vs. 15% at 12 months ( p < 0.001, 0.001, 0.005 and p = 0.14), respectively. Craving during the first 8 days was significantly reduced among highly dependent smokers on active treatment compared to placebo. Baseline mucosal lesions among abstinent subjects were reduced during the treatment period and at the non-treatment follow-up. Adverse events were mild and tolerable, the most common being irritation and soreness in the mouth and throat. Conclusion. The nicotine sublingual tablet increased the smoking cessation rate compared to placebo, reduced craving in highly dependent smokers and was well tolerated. [source] Combination therapy with ribavirin and interferon in a cohort of children with hepatitis C and haemophilia followed at a pediatric haemophilia treatment centerHAEMOPHILIA, Issue 1 2004J. Puetz Summary., Nearly all children with bleeding disorders who received factor concentrates prior to the late 1980s were infected with hepatitis C. Treatment of adults infected with hepatitis C with combination therapy consisting of ribavirin and interferon has shown sustained response rates of 30,60%. Little data is available on the response of children infected with hepatitis C treated with combination therapy, especially those with bleeding disorders. We wish to report a single paediatric haemophilia treatment center's results of treatment of adolescents with haemophilia and hepatitis C infection with combination therapy. All patients followed at the haemophilia treatment center with hepatitis C, who were human immunodeficiency virus (HIV) negative and had a measurable hepatitis C viral load were eligible. Study patients received at least 6 months of 3 MU interferon- , via subcutaneous injection three times per week and 1000 mg day,1 of ribavirin. Eleven patients agreed to participate in the study. Three patients had an un measurable viral load after 6 months of combination therapy. All three completed 12 months of medication and continued to remain free of hepatitis C for 12 months after discontinuation of therapy. Side-effects of combination therapy were significant but tolerable. The sustained response rate in this study is similar to the historical response rate seen in adults but less than the other reported response rates seen in children treated with combination therapy. Given the toxicity of combination therapy, and natural history of hepatitis C infection in children, consideration of a liver biopsy to evaluate disease progression prior to considering antiviral medications is warranted. [source] Application of unsedated transnasal esophagogastroduodenoscopy in the diagnosis of hypopharyngeal cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 2 2009Cheng-Ping Wang MD Abstract Background This study evaluates the efficacy of unsedated transnasal esophagogastroduodenoscopy (EGD) in the diagnosis of hypopharyngeal cancer and screening of esophageal lesions. Methods Twenty-seven patients with newly diagnosed hypopharyngeal cancer were evaluated by transnasal EGD without conscious sedation. Results Twenty-two hypopharyngeal cancers arose from the pyriform sinus, and the other 5 tumors were from the posterior hypopharyngeal wall. Seventeen tumors were classified as T3-T4. Twenty-four hypopharyngeal tumors were pathologically proved malignancy by this technique. Regarding simultaneous esophageal lesions, esophageal dysplasia was noted in 4 patients and esophageal cancer occurred in 6 patients. The procedures were performed without difficulty except in 1 patient with huge posterior wall tumor. The mean procedure time was 22 minutes. All patients tolerated the procedure well, without significant bleeding or respiratory distress during examination. Conclusion Unsedated transnasal EGD is a safe, tolerable, and accurate endoscopic technique for diagnosis of hypopharyngeal cancer and screening of simultaneous esophageal cancer. © 2008 Wiley Periodicals, Inc. Head Neck, 2009 [source] Concomitant low-dose cisplatin and three-dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck: Analysis of survival and toxicity,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2006Harold Lau MD Abstract Background. Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) with minimal toxicity to achieve rates of overall survival comparable to other schedules. Methods. The chemoradiotherapy schedule consisted of daily radiation to 70 Gy over 7 weeks with concurrent cisplatin 20 mg/m2 during days 1 to 4 of weeks 1 and 5. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group (RTOG) and common toxicity criteria (CTC) grading. The overall, disease-specific, and locoregional recurrence,free survival were calculated using the STATA statistics package. Possible factors influencing these endpoints were analyzed. Results. Fifty-seven patients were treated, and 56 patients were evaluable for follow-up. Median follow-up of alive patients was 16.1 months. There was an 82% complete response rate to chemoradiotherapy. The 2-year Kaplan,Meier overall, disease-specific, and locoregional recurrence,free survival rates were 62%, 67%, and 63%. Acute grade 3 and 4 radiation toxicity was noted in 61% and 2%, respectively. Grade 3 or 4 hematologic toxicity was noted in 7% of patients. Factors influencing overall survival included: Karnofsky performance status, receiving more than 50% of planned chemotherapy, age, and initial hemoglobin level. Conclusion. This regimen is tolerable and achieves overall survival and locoregional control rates comparable to other chemoradiotherapy schedules. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2002FRCPC, Samy El-Sayed MD Abstract Background Mucositis occurs in almost all radiotherapy-treated head and neck cancer patients, in approximately 75% of patients receiving hematopoietic marrow transplantation, and in approximately 40% of all patients who receive chemotherapy. Mucositis is painful, may affect all oral functions, and is a dose- and rate-limiting toxicity of therapy for cancer. Radiation-associated mucositis (onset, intensity, and duration) has been shown in recent clinical trials to be modified by the use of antibacterial/antifungal lozenges. Purpose The aim of this collaborative two-center phase II study was to assess the toxicity and microbiologic efficacy of an economically viable antimicrobial lozenge in the management of patients receiving radiation therapy for head and neck cancer. Materials and Methods Seventeen patients scheduled to receive radical or postoperative radiotherapy were provided with bacitracin, clotrimazole, and gentamicin (BCoG) lozenges (one lozenge dissolved in the mouth qid from day 1 of radiotherapy until completion). Ease of use and palatability of the lozenges, patients' symptoms (swallowing and pain), and quantitative and qualitative microbiologic evaluation of an oral rinse collection was conducted at least once weekly during radiation therapy. Results No significant side effects were reported from the use of the lozenges. The lozenges were well tolerated at the beginning of treatment by all patients, with some minor difficulty associated with oral discomfort toward the end of the treatment. Microbiologic evaluation showed consistent elimination of yeast organisms in all patients. In four patients there was no growth of gram-negative bacilli on culture, whereas in two patients, fluctuating counts were seen, and one patient had increased counts. The remaining patients had significant reduction in the gram-negative bacilli counts. Conclusions This study demonstrated that the BCoG lozenge is tolerable and microbiologically efficacious, achieving elimination of Candida in all patients and reduction in gram-negative flora in most patients. A phase III study is underway to evaluate the clinical efficacy of this lozenge. © 2002 John Wiley & Sons, Inc. Head Neck 24: 6,15, 2002. [source] Effectiveness and tolerability of paroxetine controlled release (CR) in the treatment of major depressive disorder: an open-label, prospective, multi-center trial in KoreaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2007Chi-Un Pae Abstract Objectives This study evaluated the effectiveness and tolerability of paroxetine controlled release (CR) for the treatment of Korean patients with major depressive disorder (MDD) in a naturalistic treatment setting. Methods One hundred and ninety patients with MDD were enrolled in this study. The Hamilton Depression Rating Scale-17 item (HAMD-17) and Clinical Global Impression-Severity (CGI-S) scores were measured at the baseline (day 0) and at weeks 1, 2, 4, and 8 (endpoint). The primary measure of effectiveness was a change in the mean HAMD-17 scores from the baseline to the endpoint. The secondary effectiveness measures included a decrease in the HAMD-17 scores of 50% or more at the endpoint compared with the baseline and a change in the mean CGI-S scores from the baseline to the endpoint. Remission was defined as a HAMD-17 score,,,7 at the endpoint. Results The HAMD-17 scores decreased by 56.5% (observed difference, OD,=,,13.3) (t,=,26.63, p,<,0.0001) from the baseline. The CGI-S scores also decreased by 50.0% (OD,=,,2.3) (t,=,24.47, p,<,0.0001). The response and remission rate at the endpoint was 64.2 and 48.4%, respectively. The adverse events were tolerable. No unexpected or serious side effects were observed. Conclusions Despite the methodological limitations, this study demonstrated that paroxetine CR is effective and tolerable for treating patients with MDD in an East Asian population. Copyright © 2007 John Wiley & Sons, Ltd. [source] Combined exposures to anti-androgenic chemicals: steps towards cumulative risk assessmentINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2010A. Kortenkamp Summary There is widespread exposure to anti-androgens, a group of chemicals able to disrupt androgen action in foetal life, with irreversible de-masculinizing consequences. Substances of concern include certain phthalates, pesticides and chemicals used in cosmetics and personal care products. Although people come into contact with several anti-androgens, chemicals risk assessment normally does not take account of the effects of combined exposures. However, a disregard for combination effects may lead to underestimations of risks and for this reason, we have assessed the feasibility of conducting cumulative risk assessment, where the focus is on considering the effects of exposure to multiple chemicals, via multiple routes and pathways. Following recent recommendations by the US National Research Council, we have, for the first time, included phthalates and other anti-androgenic chemicals, a total of 15 substances. On the basis of exposure estimates for the individual chemicals and reference doses for anti-androgenicity, we have used the hazard index approach. We show that the cumulative risks from anti-androgen exposures exceed acceptable levels for people on the upper end of exposure levels. The value obtained for median exposures to the 15 substances can be judged tolerable. However, significant knowledge gaps exist that prevent us from arriving at definitive conclusions. Of greatest concern is an absence of appropriate in vivo toxicity data about large numbers of in vitro androgen receptor antagonists. Knowledge about the effect profiles of these chemicals will lead to higher risk estimates. Our analysis suggests that risk reductions can be achieved by limiting exposures to the plasticizer diethyl hexyl phthalate, the cosmetic ingredients butyl- and propyl paraben, the pesticides vinclozolin, prochloraz and procymidone and bisphenol A. [source] Tolerability and safety of fluvoxamine and other antidepressantsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2006H. G. M. Westenberg Summary Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity. [source] Method for moderation: measuring lifetime risk of alcohol-attributable mortality as a basis for drinking guidelinesINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2008Jürgen Rehm Abstract The objective of this paper was to determine separately the lifetime risk of drinking alcohol for chronic disease and acute injury outcomes as a basis for setting general population drinking guidelines for Australia. Relative risk data for different levels of average consumption of alcohol were combined with age, sex, and disease-specific risks of dying from an alcohol-attributable chronic disease. For injury, combinations of the number of drinks per occasion and frequency of drinking occasions were combined to model lifetime risk of death for different drinking pattern scenarios. A lifetime risk of injury death of 1 in 100 is reached for consumption levels of about three drinks daily per week for women, and three drinks five times a week for men. For chronic disease death, lifetime risk increases by about 10% with each 10-gram (one drink) increase in daily average alcohol consumption, although risks are higher for women than men, particularly at higher average consumption levels. Lifetime risks for injury and chronic disease combine to overall risk of alcohol-attributable mortality. In terms of guidelines, if a lifetime risk standard of 1 in 100 is set, then the implications of the analysis presented here are that both men and women should not exceed a volume of two drinks a day for chronic disease mortality, and for occasional drinking three or four drinks seem tolerable. Copyright © 2008 John Wiley & Sons, Ltd. [source] Highly Efficient Synthesis of Quaternary ,-Hydroxy Phosphonates via Lewis Acid-Catalyzed Hydrophosphonylation of KetonesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 16 2009Xin Zhou Abstract A Lewis acid catalyst has been first applied to the hydrophosphonylation of ketones, giving the corresponding quaternary ,-hydroxy phosphonates in high yields (up to 98%). The present method was highly tolerable for functionalized ketones. Moreover, the first catalytic enantioselective hydrophosphonylation of an unactivated ketone was also realized by using a tridentate Schiff base-titanium complex. [source] Prospective study of short-term peginterferon-,-2a monotherapy in patients who had a virological response at 2 weeks after initiation of interferon therapyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2008Soocheol Jeong Abstract Background and Aims:, Long-term interferon (IFN) therapy is effective in eliminating hepatitis C virus (HCV). However, it carries the risk of adverse effects and reduced quality of life. To assess whether short-term IFN therapy effectively eliminates HCV, we performed a prospective pilot study of pegylated (peg)IFN-,-2a therapy for 8 or 24 weeks. Methods:, After excluding patients with high titers of genotype-1, 55 HCV patients received pegIFN-,-2a. Patients who became negative for HCV-RNA at week 2 were allocated to either an 8-week (n = 19) or 24-week (n = 15) course of IFN. We evaluated the efficacy of and tolerance to IFN therapy. Results:, The sustained virological response rate was excellent in the two groups (8 weeks, 89.5% [17/19]; 24 weeks, 100% [15/15], respectively,). IFN dose reduction was required in one patient of the 8-week group, but in six patients of the 24-week group (P = 0.028). Treatment was completed by all patients of the 8-week group, but discontinued in five patients of the 24-week group (P = 0.011). Conclusions:, The 8-week IFN therapy is more tolerable than the 24-week therapy and had similar outcomes. Excluding the patients with high titers of genotype-1, we recommend switching to an 8-week course of pegIFN-, monotherapy once patients show an ultra rapid virological response at week 2 from the start of IFN therapy. [source] Antiviral maintenance treatment with interferon and ribavirin for recurrent hepatitis C after liver transplantation: Pilot studyJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 12 2007Arno Kornberg Abstract Background:, The aim of this pilot study was to evaluate efficacy of a long-term antiviral maintenance therapy (AMT) with interferon-,2b and ribavirin in liver transplant recipients with recurrent hepatitis C. Methods:, Twenty-one patients with recurrent hepatitis C after liver transplantation received AMT with interferon and ribavirin, following 12 months of a basic antiviral combination treatment. Allograft function, viremia loads and allograft morphology were evaluated continuously. Results:, After 12 months of basic antiviral therapy, 14 patients (66.6%) had achieved initial clearance of viremia levels, and 17 recipients (81%) demonstrated normalization of allograft function, respectively. Inflammation score declined significantly (6.0 vs 3.9; P = 0.002), while stage of fibrosis remained unchanged. In virological responders maintenance therapy led to further regression of inflammation score (4.0 at baseline vs 3.1 at 24 months AMT) and fibrosis score (1.6 at baseline vs 1.1 at 24 months AMT). Despite persistence of viremia levels, continued antiviral therapy prevented progression to severe allograft inflammation in virological non-responders. Hematologic adverse effects resulted in treatment discontinuation in seven patients (33.3%). Conclusion:, Long-term AMT, if tolerable, might be an effective approach for preventing progression to severe allograft fibrosis and thereby improving long-term survival in liver transplant recipients with recurrent hepatitis C. [source] 55 Ice age kelp forests: climate-driven changes in kelp forest distribution since the last glacial maximumJOURNAL OF PHYCOLOGY, Issue 2003M. H. Graham Kelp forest distributions are constrained by the availability of rocky substrate within the depth range tolerable for growth and reproduction, which can vary over relatively short geological timescales (millennia) due to interactions between coastal bathymetry and climate-driven changes in eustatic sea level. Using GIS, a digital bathymetric map, sea level curves, and published kelp depth tolerances, I reconstructed changes in the size and distribution of giant kelp (Macrocystis pyrifera) forests in the Southern California Bight since the last glacial maximum. Reconstructions predicted that the total area of available kelp forest habitat for the California Channel Islands during the last glacial maximum (18.5 kyr BP; 628 square km) was greater than at present (382 square km) but less than at 16.5 kyr BP (1130 square km). Available kelp forest habitat along the southern California mainland also increased rapidly from 18.5 to 16.5 kyr BP but continued to increase with sea level rise. Differences in the effects of sea level rise on coastal geomorphology between the islands and mainland further constrained the extent of rocky substrate available to kelps. Given biomass and productivity estimates from present-day kelp forests, these reconstructions suggest more productive and spatially extensive island kelp forests near the last glacial maximum than at present, but the opposite pattern for the mainland. These climate-driven changes in kelp forest distribution and productivity likely had important historical impacts on the ecology and evolution of the present-day kelp ecosystem including kelp forest exploitation by early human inhabitants of southern California. [source] The pharmacokinetics and safety of porfimer after repeated administration 30,45 days apart to patients undergoing photodynamic therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010S. P. Pereira Summary Background, Porfimer is an intravenous (i.v.) injectable photosensitizing agent used in the photodynamic treatment of tumours and of high-grade dysplasia in Barrett's oesophagus. Aim, To assess the pharmacokinetics as well as the safety profiles of porfimer after a first and a second dose administered 30,45 days apart in patients undergoing photodynamic therapy. Methods, Nineteen patients (16 with cholangiocarcinoma) were enrolled. Porfimer sodium was administered by i.v. injection over 3,5 min. Blood samples were collected prior to starting i.v. drug injection and postdose at different time points after the first and second administrations. Results, Porfimer exposure values after the second administration were statistically higher than those observed after the first administration, suggesting a slight accumulation of porfimer following repeated administration. The apparent mean elimination half-life of porfimer increased from 410 h after the first administration to 725 h after the second administration. The safety profiles of porfimer after a first and a second administration were similar and did not raise additional concern. Eight patients experienced nine serious adverse events. Only photosensitivity was deemed study-drug related. Conclusion, Porfimer appears to display a safe and tolerable profile when used in patients requiring a second photodynamic therapy within 45 days. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 62JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003C Briani Thalidomide seems to be effective in the treatment of cutaneous forms of lupus erythematosus refractory to other therapies. Peripheral neuropathy is the most severe side effect, but the incidence of neuropathy and its relation to thalidomide doses are still unclear. We prospectively monitored 12 patients treated with thalidomide for cutaneous lupus erythematosus in order to estimate the occurrence of side effects, particularly peripheral neuropathy. A total of 12 female patients, median age 38,6 years (range 26,56), with subacute or chronic cutaneous lupus erythematosus were considered. The patients were treated with low dose thalidomide (starting dose 100 mg, tapered to 50 mg/day or 50 mg alternative day) for up to 18 months. The average follow-up period was 8,6 months (range 2,18). Prior to, and regularly during treatment patients underwent neurological evaluation and electrophysiological study of at least 8 nerves in the 4 arms (ulnar, median, sural, peroneal nerves). At recruitment, one patient presented a sensory-motor peripheral neuropathy. Of the remaining 11 patients, six did not present electrophysiological evidence of neuropathy, one had a carpal tunnel syndrome and four showed slowing of ulnar nerve velocity at elbow. No patients developed neuropathy neither worsening of electrophysiological parameters during thalidomide treatment. The most common side effect was tremor, always reversible after withdrawing or reducing thalidomide. Paresthesias, somnolence, amenhorrea, constipation were also present. Only one patient had to stop the therapy for the occurrence, 10 days after taking 50 mg of thalidomide, of a severe, stabbing, "zoster-like" thoracic pain, which disappeared upon withdrawal of the drug. Started again on thalidomide, the symptoms reappeared and the patient definitely interrupted the therapy with benefit. All the 11 patients who continued on the therapy presented a significant improvement or remission of the cutaneous alterations. These preliminary data seem to indicate that low dose thalidomide is efficacious and tolerable for cutaneous lupus erythematosus. Peripheral neuropathy seems not to be a major side effect. A longer follow-up and the study of more patients are needed to confirm the results. [source] Setting school-level outcome standardsMEDICAL EDUCATION, Issue 2 2006David T Stern Background, To establish international standards for medical schools, an appropriate panel of experts must decide on performance standards. A pilot test of such standards was set in the context of a multidimensional (multiple-choice question examination, objective structured clinical examination, faculty observation) examination at 8 leading schools in China. Methods, A group of 16 medical education leaders from a broad array of countries met over a 3-day period. These individuals considered competency domains, examination items, and the percentage of students who could fall below a cut-off score if the school was still to be considered as meeting competencies. This 2-step process started with a discussion of the borderline school and the relative difficulty of a borderline school in achieving acceptable standards in a given competency domain. Committee members then estimated the percentage of students falling below the standard that is tolerable at a borderline school and were allowed to revise their ratings after viewing pilot data. Results, Tolerable failure rates ranged from 10% to 26% across competency domains and examination types. As with other standard-setting exercises, standard deviations from initial to final estimates of the tolerable failure rates fell, but the cut-off scores did not change significantly. Final, but not initial cut-off scores were correlated with student failure rates (r = 0.59, P = 0.03). Discussion, This paper describes a method to set school-level outcome standards at an international level based on prior established standard-setting methods. Further refinement of this process and validation using other examinations in other countries will be needed to achieve accurate international standards. [source] Reversal of Sleep-Disordered Breathing with Opioid WithdrawalPAIN PRACTICE, Issue 5 2009Kannan Ramar MD Abstract Obstructive sleep apnea, central sleep apnea, sleep related hypoventilation, Biot's or ataxic breathing, and cluster breathing are some of the commonly described sleep disorders in patients who are on long-term opioids. Continuous positive airway pressure that is commonly used to treat obstructive sleep apnea may not be effective in treating sleep-disordered breathing in long-term opioid users, and an adaptive servoventilator (ASV) may be needed. We present a 30-year-old woman with excessive daytime sleepiness and sleep-disordered breathing for the past 4 years. Medical history was complicated by chronic osteomyelitis, periorbital abscess, and chronic facial pain requiring methadone for pain control for the last 4 years. In this case, ASV, though effective, was not tolerable due to chronic facial pain, and successful withdrawal of methadone at our pain rehabilitation center resolved the sleep-disordered breathing and improved daytime sleepiness. This is to our knowledge the first case report of resolution of sleep-disordered breathing and improvement in daytime sleepiness after withdrawal of long-term opioid use. [source] Hypersaline nasal irrigation in children with symptomatic seasonal allergic rhinitis: A randomized studyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 2 2003Werner Garavello Recent evidence suggests that nasal irrigation with hypertonic saline may be useful as an adjunctive treatment modality in the management of many sinonasal diseases. However, no previous studies have investigated the efficacy of this regimen in the prevention of seasonal allergic rhinitis-related symptoms in the pediatric patient. Twenty children with seasonal allergic rhinitis to Parietaria were enrolled in the study. Ten children were randomized to receive three-times daily nasal irrigation with hypertonic saline for the entire pollen season, which had lasted 6 weeks. Ten patients were allocated to receive no nasal irrigation and were used as controls. A mean daily rhinitis score based on the presence of nasal itching, rhinorrea, nasal obstruction and sneezing was calculated for each week of the pollen season. Moreover, patients were allowed to use oral antihistamines when required and the mean number of drug assumption per week was also calculated. In patients allocated to nasal irrigation, the mean daily rhinitis score was reduced during 5 weeks of the study period. This reduction was statistically significantly different in the 3th, 4th and 5th week of therapy. Moreover, a decreased consumption of oral antihistamines was observed in these patients. This effect became evident after the second week of treatment and resulted in statistically significant differences during the 3th, 4th and 6th week. This study supports the use of nasal irrigation with hypertonic saline in the pediatric patient with seasonal allergic rhinitis during the pollen season. This treatment was tolerable, inexpensive and effective. [source] AMG 531: An investigational thrombopoiesis-stimulating peptibodyPEDIATRIC BLOOD & CANCER, Issue S5 2006Janet L. Nichol MSArticle first published online: 24 AUG 200 Abstract Thrombopoietin (TPO) regulates megakaryopoiesis and the generation of platelets. Recombinant TPO has been investigated in clinical studies for use in thrombocytopenia with limited success. A new peptibody, AMG 531, has been shown to increase platelet counts in preclinical and Phase 1 and Phase 2 studies and to be generally safe and tolerable in those studies. Pediatr Blood Cancer 2006;47:723,725. © 2006 Wiley-Liss, Inc. [source] A Novel Gel Formulation of 0.25% Tretinoin and 1.2% Clindamycin Phosphate: Efficacy in Acne Vulgaris Patients Aged 12 to 18 YearsPEDIATRIC DERMATOLOGY, Issue 3 2009Lawrence F. Eichenfield M.D. Recently, the US FDA approved the combination of 1.2% clindamycin (CLIN) and 0.025% tretinoin (RA) in a novel gel formulation for the treatment of mild to moderate acne, based on results from two 12-week, multicenter, double-blind Phase 3 trials in which patients were randomized to four treatment arms: CLIN/RA, CLIN, RA, and vehicle. The trials studied more than 4500 patients 12 years of age or older. In both trials, CLIN/RA gel produced significantly greater clinical improvements than vehicle or either monotherapy. CLIN/RA was safe and well tolerated in both trials and in a 52-week safety follow-up evaluation. The current study is a subgroup analysis that evaluates CLIN/RA's effects on acne lesion prevalence in 12- to 18-year-old patients with mild to severe baseline acne severity. CLIN/RA significantly reduced the number of inflammatory, noninflammatory, and total acne lesions after 12 weeks of treatment (p , 0.004) in 1,710 patients aged 12 to 18 years. Relatively greater improvements were seen following CLIN/RA treatment compared to CLIN or RA monotherapy, or the vehicle gel beginning as early as 2 weeks following treatment initiation. This novel CLIN/RA gel for treating acne is tolerable and safe and offers clinicians and teen aged patients a new and efficacious intervention for acne vulgaris. [Abstract amended after online publication date June 8, 2009] [source] Strong excitonic mixing effect in asymmetric double quantum wells: On the optimization of electroabsorption modulatorsPHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 7 2008Dong Kwon Kim Abstract We investigate the mixing of excitons originating in different subband pairs in asymmetric double quantum wells (ADQWs) in a range of electric field where the two lowest exciton states anticross. This excitonic mixing is mainly attributed to the Coulomb interactions between subbands and the valence-subband nonparabolicity. Results show that excluding the excitonic mixing effect results in significant error in both the energies and the oscillator strengths of the excitons in an ADQW with thick barrier (3 nm). Even in an ADQW with a fairly thin barrier (1.2 nm), the error in the oscillator strengths can be substantial, although the errors in the computed energies may be tolerable. We find that including the mixing of excitons is indispensable in optimizing the structures of the asymmetric double quantum well electroabsorption modulators. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Pulsed dye laser treatment for viral warts: A study of 120 patientsTHE JOURNAL OF DERMATOLOGY, Issue 8 2008Hyun Su PARK ABSTRACT A prospective, non-blinded, non-randomized study on 120 wart patients treated with pulsed dye laser was performed to evaluate the efficacy and safety of pulsed dye laser treatment for viral warts and to demonstrate the proper application and effective technique of this method. The overall clearance rate was 49.5%. The clearance rates of flat warts, periungual warts, plantar warts and common warts were 67.6%, 51.1%, 47.6% and 44.3%, respectively. Overall, the response rates of pediatric warts, recalcitrant warts and old warts were superior to those of adult warts, simple warts and non-old warts, respectively; however, those trends were not statistically significant. We concluded that pulsed dye laser treatment is a safe, tolerable and relatively effective treatment method for viral warts. Pulsed dye laser treatment may be a more efficacious method for flat warts and recalcitrant periungual warts, and it can be an effective modality for newly-developed warts. The highest clearance rate was noted at a fluence of 9.5 J/cm2 (P , 0.05) and it is recommended that practitioners perform pulsed dye laser treatments for viral warts at the fluences of 9.0,9.5 J/cm2. A replacement of pulsed dye laser treatment should be considered unless prominent improvement is observed after three treatment sessions. [source] Randomized controlled trial of neoadjuvant chemotherapy with cisplatin and vinorelbine in patients with stage IIIA non-small cell lung cancer in ChinaASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2009Jian LI Abstract Aim: The aim of this study was to evaluate the efficacy of cisplatin plus vinorelbine as a regimen of neoadjuvant chemotherapy on the improvement of surgical resectability and survival in Chinese patients with stage IIIA non-small cell lung cancer (NSCLC). Methods: Fifty-six patients with stage IIIA NSCLC were randomly assigned to undergo either surgery preceded by two cycles of chemotherapy with cisplatin plus vinorelbine (the neoadjuvant chemotherapy arm) or immediate surgery (the primary surgery arm). The patients who had a complete resection received two to four cycles of chemotherapy, and those with incomplete resection received radiotherapy followed by two cycles of chemotherapy after surgery. Results: The overall response rate to neoadjuvant chemotherapy was 53.6%, with a complete response of 7.1%. A pathological complete response was seen in two patients (8%). The complete resection rates were 78.6% in the neoadjuvant chemotherapy arm and 60.7% in the primary surgery arm. The median overall survival and median disease-free survival was 30 months and 24 months, respectively, in the neoadjuvant chemotherapy arm as compared to 16 months and 11 months in the primary surgery arm (P = 0.04 and P = 0.048). The 3-year and 5-year survival rate was 49.7% and 31.9%, respectively, for the neoadjuvant chemotherapy arm and 29.2% and 3.6% for the primary surgery arm. Conclusion: Neoadjuvant chemotherapy with cisplatin plus vinorelbine regimen is effective and tolerable and can improve the overall survival and disease-free survival time in Chinese patients with stage IIIA NSCLC. [source] Phase II study of S-1 and irinotecan combination chemotherapy as a first-line therapy for patients with advanced gastric cancer.ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Korean Cancer Study Group Protocol ST05-0 Abstract Background: Irinotecan plus intravenous 5-fluorouracil (5-FU) with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative and has a high response rate of about 40% for patients with advanced gastric cancer (AGC). We evaluated the antitumor activity and toxicities of an S-1 and irinotecan combination as a first-line therapy for patients with AGC. Methods: Patients with histologically confirmed unresectable or metastatic AGC were treated with S-1 40 mg/m2 PO twice daily on days 1,14 and irinotecan 150 mg/m2 i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities resulted. Results: A total of 45 patients were enrolled between September 2005 and March 2007. After a median of seven cycles of chemotherapy (range: 1,20, total: 350), 42 and 44 patients were evaluable for response and toxicity, respectively. On the intention-to-treat analysis, the overall response rate was 48.9% (95% C.I. 34.3,63.5%). The median time to progression was 5.7 months (95% C.I. 4.3,7.1) and the median overall survival was 10.4 months (95% C.I. 6.1,14.7). The commonly observed grade 3/4 adverse events were neutropenia (29.5% of patients) and vomiting (13.6%). Conclusion: An S-1 and irinotecan combination chemotherapy is active and tolerable as a first-line therapy for AGC. [source] A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorderBIPOLAR DISORDERS, Issue 3 2010Eduard Vieta Vieta E, Nuamah IF, Lim P, Yuen EC, Palumbo JM, Hough DW, Berwaerts J. A randomized, placebo- and active-controlled study of paliperidone extended release for the treatment of acute manic and mixed episodes of bipolar I disorder. Bipolar Disord 2010: 12: 230,243. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives:, To evaluate the antimanic efficacy and safety of paliperidone extended-release (ER) tablets in patients with bipolar I disorder. Methods:, This study included a 3-week, double-blind, acute treatment phase (paliperidone ER versus placebo, with quetiapine as control), and a 9-week, double-blind, maintenance phase (paliperidone ER versus quetiapine). Patients [n = 493; Young Mania Rating Scale (YMRS) score , 20] were randomized (2:2:1) to flexibly dosed paliperidone ER (3,12 mg/day), quetiapine (400,800 mg/day), or placebo for the acute treatment phase. During the maintenance phase, patients assigned to placebo were switched to paliperidone ER but not included in analysis of efficacy. Results:, Paliperidone ER was superior to placebo at the 3-week endpoint {primary outcome; least-squares mean difference in change from baseline in YMRS scores [95% confidence interval (CI)]: ,5.5 (,7.57; ,3.35); p < 0.001} and noninferior to quetiapine at the 12-week endpoint [least-squares mean difference (95% CI): 1.7 (,0.47; 3.96)]. The median mode dose during the 12-week treatment period was 9 mg for paliperidone ER and 600 mg for quetiapine. The most common (, 10%) treatment-emergent adverse events during the 12-week period were: headache (16%), somnolence (10%), and akathisia (10%) for paliperidone ER; somnolence (21%), sedation and dry mouth (17% each), headache (14%), and dizziness (13%) for quetiapine. Body weight increase , 7% from baseline to 12-week endpoint was 8% with paliperidone ER and 17% with quetiapine. A higher percentage of paliperidone ER (13.9%) versus quetiapine patients (7.5%) ,switched to depression' at the12-week endpoint. Conclusions:, Paliperidone ER (3,12 mg/day) was efficacious and tolerable in the treatment of acute mania. [source] The role of capsaicin-sensitive afferents in autonomic dysreflexia in patients with spinal cord injuryBJU INTERNATIONAL, Issue 7 2003Y. Igawa OBJECTIVES To determine whether capsaicin-sensitive nerves in the bladder form the afferent limb involved in autonomic dysreflexia (AD) in patients with spinal cord injury (SCI). PATIENTS AND METHODS Seven men with SCI (five cervical cord, two thoracic cord) with AD and detrusor hyper-reflexia (DH) were enrolled. Under general anaesthesia, capsaicin solution (100 mL of 2 mmol/L in 10% ethanol) was instilled in the bladder and retained for 30 min. The patients were assessed by medium-fill cystometry (CMG) just before and 50 min after the capsaicin treatment. Intra-arterial blood pressure (BP) and heart rate were monitored continuously throughout the procedure; 10% ethanol was instilled before capsaicin treatment in four patients as a control. Serum catecholamines were measured during bladder filling and capsaicin treatment, and the blood ethanol concentration also measured after instillation in all patients. The CMG with concomitant monitoring of BP and heart rate was repeated 1 week, 1, 3, 6, 12 and 24 months after instillation. In two patients the instillations were repeated 5 and 12 months after the first because of recurrence of DH. Urodynamic variables assessed were maximum cystometric capacity (MCC), maximum amplitude of uninhibited detrusor contraction (UICmax), the bladder capacity at 40 cmH2O detrusor pressure (Cdp40) and a systolic BP of> 140 mmHg or diastolic BP of> 90 mmHg (CHT). RESULTS There was an increase in BP and a decrease in heart rate in all patients during bladder filling before capsaicin treatment. Instillation of capsaicin produced a significant increase in both systolic and diastolic BP and a significant decrease in heart rate. The maximum cardiovascular effects were at 5,10 min after instillation and gradually returned to baseline within 40 min. The vehicle had negligible effects on either BP or heart rate. After capsaicin treatment, the responses of BP and heart rate to bladder distension were significantly reduced. Both serum catecholamine values and the blood ethanol concentration remained within normal limits. The mean (range) follow-up after the first treatment was 15 (6,30) months. One month after treatment all seven patients became continent and their episodes of AD became negligible and well tolerable between catheterizations (for 3,4 h); the effects lasted for , 3 months in all. MCC was significantly increased at 4 weeks and 3 months, and UICmax significantly decreased at 4 weeks after treatment. Both mean Cdp40 and CHT increased 1 week, 1 and 3 months after treatment. Two patients received a second instillation, and have been continent with no symptomatic AD for 6 and 24 months. The remaining five patients have been continent with no symptomatic AD for 6,12 months. CONCLUSION These results indicate that intravesical capsaicin, but not the vehicle, acutely triggers AD in patients with SCI, suggesting involvement of bladder capsaicin- sensitive afferents in AD in these patients. The results also suggest that intravesical capsaicin may be a promising therapy for both AD and DH in such patients. Further long-term follow-up studies are needed to evaluate the duration of its effect. [source] A phase I study of vorinostat in combination with idarubicin in relapsed or refractory leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2010Tapan M. Kadia Summary Histone deacetylase inhibitors (HDACi) affect chromatin remodelling and modulate the expression of aberrantly silenced genes. HDACi have single-agent clinical activity in haematological malignancies and have synergistic anti-leukaemia activity when combined with anthracyclines in vitro. We conducted a two-arm, parallel Phase I trial to investigate two schedules of escalating doses of vorinostat (Schedule A: thrice daily (TID) for 14 d; B: TID for 3 d) in combination with a fixed dose of idarubicin in patients with refractory leukaemia. Of the 41 patients enrolled, 90% had acute myeloid leukaemia, with a median of 3 prior therapies. Seven responses (17%) were documented (two complete response (5%), one complete response without platelet recovery (2·5%), and four marrow responses). The 3-d schedule of vorinostat was better tolerated than the 14-d schedule. The maximum tolerated dose for vorinostat was defined as 400 mg TID for 3 d. The most common grade 3 and 4 toxicities included mucositis, fatigue and diarrhoea. Correlative studies demonstrated histone acetylation in patients on therapy and modulation of CDKN1A and TOP2A (topoisomerase II) gene expression. Pharmacokinetic analysis confirmed a dose-related elevation in plasma vorinostat concentrations. The combination of vorinostat and idarubicin is generally tolerable and active in patients with advanced leukaemia and should be studied in the front-line setting. [source] | |||||||||||||||||||||||||||||||||||||