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Therapeutic Response (therapeutic + response)
Selected AbstractsNanoshells with Targeted Simultaneous Enhancement of Magnetic and Optical Imaging and Photothermal Therapeutic ResponseADVANCED FUNCTIONAL MATERIALS, Issue 24 2009Rizia Bardhan Abstract Integrating multiple functionalities into individual nanoscale complexes is of tremendous importance in biomedicine, expanding the capabilities of nanoscale structures to perform multiple parallel tasks. Here, the ability to enhance two different imaging technologies simultaneously,fluorescence optical imaging and magnetic resonance imaging,with antibody targeting and photothermal therapeutic actuation is combined all within the same nanoshell-based complex. The nanocomplexes are constructed by coating a gold nanoshell with a silica epilayer doped with Fe3O4 and the fluorophore ICG, which results in a high T2 relaxivity (390,mM,1,s,1) and 45× fluorescence enhancement of ICG. Bioconjugate nanocomplexes target HER2+ cells and induce photothermal cell death upon near-IR illumination. [source] Levetiracetam in the Treatment of Idiopathic Generalized EpilepsiesEPILEPSIA, Issue 2005Richard Grünewald Summary:, Since its introduction into clinical practice in 1999, levetiracetam, the S enantiomer of piracetam, has rapidly found a secure place, initially in the therapy of partial onset seizures and subsequently in the treatment of idiopathic generalized epilepsies (IGE). It has many of the properties of an "ideal" antiepileptic drug, including rapid absorption, linear pharmokinetics, and sparse drug interactions. Tolerabiliy is generally excellent in both adults and children, although tiredness is a common dose-limiting adverse effect. Occasionally the drug can precipitate behavioral abnormalities, especially in patients with learning disability. There is a wide safety margin in overdose. In common with most antiepileptic drugs its mode of action remains uncertain. Levetiracetam binds to a specific site in the brain, influences intracellular calcium currents and reverses negative allosteric modulators of GABA- and glycine-gated currents in vitro. Its effectiveness has been demonstrated in animal models of epilepsy and in clinical trials of partial onset and IGE. Treatment of IGEs may be straightforward, with many patients demonstrating an excellent and robust response to valproate monotherapy. However, there remains a significant minority of patients for whom valproate is unsuitable, including those who experience unacceptable adverse effects (e.g., weight gain or hair loss) and women of childbearing age in whom the teratogenic potential of valproate is unacceptable. Therapeutic response to lamotrigine in this group is often disappointing, and many clinicians now are turning to the choice of levetiracetam. Efficacy in generalized tonic,clonic seizures and myoclonus is usually apparent and some patients experience improvement in typical absences. Experience of combinations of levetiracetam with other antiepileptic drugs is limited in IGE and the responses are largely anecdotal. In our hands, patients with refractory IGEs may respond to combinations of levetiracetam with valproate, lamotrigine, and phenobarbital, and adverse effects when they occur are usually limited to tiredness. Levetiracetam does not interact with the oral contraceptive pill, simplifying treatment in women of childbearing age. Although animal data look encouraging, questions over levetiracetam's teratogenic potential and overall safety in pregnancy will remain for many years to come. [source] Evaluation of a 1-h exposure time to mechlorethamine in patients undergoing topical treatmentBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2002P. Foulc SummaryBackground Mechlorethamine is frequently used in the treatment of cutaneous lymphoma, but its application is limited in 30,80% of cases because of cutaneous intolerance. Reducing the concentration to avoid this side-effect has been only modestly successful. Objectives To investigate whether a shorter application period could reduce the frequency of intolerance. Methods In an open prospective study in 39 patients with cutaneous T-cell lymphoma or parapsoriasis, mechlorethamine was applied according to the usual practices of the participating physicians (number of weekly applications, treatment confined to lesions or performed over the entire body) and then washed off after 1 h in all cases. Results Cutaneous intolerance was observed in 19 of 39 patients (49%). Six of these patients showed allergic contact dermatitis to mechlorethamine after a mean period of 9·3 weeks, while the other 13 developed irritant contact dermatitis after a longer period. Cutaneous intolerance did not differ significantly according to the number of applications per week or the extent of body area treated. The therapeutic response rate was 69%, and no difference in therapeutic efficacy was noted between daily and intermittent applications. Conclusions Comparison with published studies showed no significant difference in the number of cases of cutaneous intolerance after short-term application, although their occurrence was delayed. Therapeutic response was decreased appreciably by short-term application as compared with results in the literature. [source] Use of therapeutic responses to glucose replacement to predict glucose patterns in diabetic patients presenting with severe hypoglycaemiaINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2009Y.-Y. Lin Summary Objective:, The purpose of this study was to determine whether initial serum glucose levels, therapeutic responses to intravenous glucose replacement and changes in serum glucose levels over time could predict serum glucose patterns. Methods:, The patients enrolled in this retrospective chart review had been previously diagnosed with diabetes mellitus and were later hospitalised for severe hypoglycaemia (SH). They were all admitted to the emergency department (ED) during a 4-year period between January 2003 and December 2006. Comparison of the therapeutic responses to glucose replacement according to the serum glucose patterns [categorised into recurrent hypoglycaemia (RH), overshoot hyperglycaemia (OH) and favourable groups] during the first 48 h was performed. Results:, Compared with the favourable group, therapeutic responses to glucose replacement were significantly lower in the RH group and higher in the OH group; the changes in serum glucose levels over time were also significantly lower in the RH group and higher in the OH group. Conclusion:, Therapeutic responses to glucose replacement and changes in serum glucose levels over time can differentiate diabetic patients with RH and OH from those with favourable glucose patterns during the first 48 h after presentation in the ED with SH. We believe that a ,response-to-treatment' based strategy is useful in determining the ED disposition of diabetic patients presenting with SH. [source] Single-Agent Pamidronate for Palliative Therapy of Canine Appendicular Osteosarcoma Bone PainJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2007Timothy M. Fan DVM Background:Canine appendicular osteosarcoma (OSA) causes focal bone destruction, leading to chronic pain and reduced quality-of-life scores. Drugs that inhibit pathologic osteolysis might provide additional treatment options for managing cancer-induced bone pain. Aminobisphosphonates induce osteoclast apoptosis, thereby reducing pain associated with malignant osteolysis in human patients with cancer. Hypothesis:Treatment of dogs with pamidronate administered intravenously will alleviate bone pain and reduce pathologic bone turnover associated with appendicular OSA in dogs. Animals:Forty-three dogs with naturally occurring appendicular OSA administered pamidronate intravenously. Methods:Prospective study. Therapeutic responses in dogs treated with pamidronate administered intravenously and nonsteroidal anti-inflammatory drugs (NSAID) were evaluated by using a numerical cumulative pain index score (CPIS), and by quantifying urine N-telopeptide (NTx) excretion and relative primary tumor bone mineral density (rBMD) assessed with dual energy x-ray absorptiometry. In addition, variables, including pamidronate dose, skeletal mass, baseline and change for CPIS, urine NTx and rBMD during treatment, and baseline tumor volume and radiographic pattern were compared between dogs clinically responsive and nonresponsive to pamidronate therapy. Results:Twelve of 43 dogs (28%) had pain alleviation for > 4 months, lasting a median of 231 days. Changes in CPIS and rBMD during treatment were statistically different between responders and nonresponders (P= .046 and .03, respectively). Conclusions and Clinical Importance: Substantiated by reductions in CPIS and increases in rBMD, single-agent pamidronate administered intravenously with NSAID therapy relieves pain and diminishes pathologic bone turnover associated with appendicular OSA in a subset of dogs. [source] Sustained ophthalmic in situ gel of ketorolac tromethamine: rheology and in vivo studiesDRUG DEVELOPMENT RESEARCH, Issue 6 2009A.S. Manjappa Abstract Most ocular diseases are treated with topical eye drops. The poor bioavailability and therapeutic response exhibited by these conventional eye drops due to rapid precorneal elimination of the drug may be overcome by the use of in situ gelling systems that are instilled as drops into the eye and undergo a sol-to-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of the nonsteroidal anti-inflammatory drug (NSAID), ketorolac tromethamine, based on the concept of pH-triggered in situ gelation. Polyacrylic acid (Carbopol® 934) was used as the gelling agent in combination with hydroxypropylmethylcellulose (Methocel E15LV), which acted as a viscosity enhancer. The prepared formulations were characterized for clarity, pH, drug content, rheology, and in vivo drug release. Clarity, pH, and drug content of the developed formulations were found to be satisfactory. The developed formulation showed pseudo-plastic rheology. The formulation with benzalkonium chloride and edetate disodium improved the rate of corneal absorption but not the extent. The developed formulation is a viable alternative to conventional eye drops by virtue of its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain drug release. Also importantly is the ease of instillation afforded and decreased frequency of instillation resulting in better patient acceptance. Drug Dev Res, 2009. © 2009 Wiley-Liss, Inc. [source] The 10 most important things known about addictionADDICTION, Issue 1 2010Doug Sellman ABSTRACT If you were asked: ,What are the most important things we know about addiction?' what would you say? This paper brings together a body of knowledge across multiple domains and arranged as a list of 10 things known about addiction, as a response to such a question. The 10 things are: (1) addiction is fundamentally about compulsive behaviour; (2) compulsive drug seeking is initiated outside of consciousness; (3) addiction is about 50% heritable and complexity abounds; (4) most people with addictions who present for help have other psychiatric problems as well; (5) addiction is a chronic relapsing disorder in the majority of people who present for help; (6) different psychotherapies appear to produce similar treatment outcomes; (7) ,come back when you're motivated' is no longer an acceptable therapeutic response; (8) the more individualized and broad-based the treatment a person with addiction receives, the better the outcome; (9) epiphanies are hard to manufacture; and (10) change takes time. The paper concludes with a call for unity between warring factions in the field to use the knowledge already known more effectively for the betterment of tangata whaiora (patients) suffering from addictive disorders. [source] Highly active antiretroviral therapy (HAART) among HIV-infected drug users: a prospective cohort study of sexual risk and injecting behaviourADDICTION, Issue 3 2006Colette Smit ABSTRACT Aims To study sexual risk and injecting behaviour among HIV-infected drug users (DU) receiving highly active antiretroviral therapy (HAART)., Design and setting As part of an ongoing prospective cohort study, HIV-infected DU who commenced HAART (n = 67) were matched with those not starting HAART (n = 130) on CD4 cell counts, duration of cohort participation, age and calendar year of visit. Immunological and virological responses of the HAART-treated DU were compared with the HAART-treated homosexual men from the same cohort (n = 212). Measurements Trends in behaviour and therapeutic response were tested with a logistic regression model adjusted for repeated measurements and a piecewise random effects model, respectively. Findings Non-HAART users reported more episodes of injecting than HAART users. In both groups injecting declined over time with no effect of HAART initiation. Before HAART initiation an increase in sexual risk behaviour was observed among those who had been assigned to receive HAART; their sexual risk behaviour declined thereafter. No change in sexual risk behaviour was found among non-HAART users. Relative to homosexual men, DU had a similar initial therapeutic response, but DU started HAART at lower CD4 cell counts and higher viral load levels. Conclusion DU who are treated with HAART are not increasing their risk behaviour, and their early response to HAART is similar to homosexual men. However, before the treated DU received HAART they were seen to inject less often than those not treated with HAART. This suggests that selection of potential HAART starters is based on limited drug use. Although the DU who commence HAART are a selected group, our results show that HIV-infected DU can be treated effectively. [source] Characterization of freezing of gait subtypes and the response of each to levodopa in Parkinson's diseaseEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2003J. D. Schaafsma To assess the effect of levodopa on distinct freezing of gait (FOG) subtypes in patients with ,off' FOG. Nineteen patients (12 men, mean age 62.0 ± 8.4 years) with Parkinson's disease and clinically significant FOG during ,off' states were videotaped whilst walking 130 m during ,off' and ,on' states. Three independent observers characterized the type, duration, and clinical manifestations and quantified FOG by analyzing the videotapes. Their combined mean scores were used for statistical analysis. The intra-class correlation coefficient assessed inter-observer reliability. Wilcoxon and Friedman tests evaluated differences in mean frequencies of FOG characteristics. During ,off' states, FOG was elicited by turns (63%), starts (23%), walking through narrow spaces (12%) and reaching destinations (9%). These respective values were only 14, 4, 2 and 1% during ,on' states (P < 0.011). Moving forward with very small steps and leg trembling in place were the most common manifestations of FOG; total akinesia was rare. Most FOG episodes took <10 s and tended to be shorter during ,on' states. Levodopa significantly decreased FOG frequency (P < 0.0001) and the number of episodes with akinesia (P < 0.001). Distinction amongst FOG subtypes enables evaluation of distinctive therapeutic response. Levodopa helps in reducing the frequency and duration of ,off'-related FOG. [source] Application of proton nuclear magnetic resonance spectroscopy to the study of Cryptococcus and cryptococcosisFEMS YEAST RESEARCH, Issue 4 2006Tania C. Sorrell Abstract Proton nuclear magnetic resonance spectroscopy is a nondestructive technique that identifies chemicals in solution and in living cells. It has been used in cryptococcal research to identify the primary structure of capsular glucuronoxylomannans, link cellular apoptosis susceptibility (CAS) genes to positioning of residues on the mannose backbone of glucuronoxylomannan, and verify that the cryptococcal virulence determinant, phospholipase B, is elaborated in vivo. Promising clinical applications include speciation (Cryptococcus neoformans and Cryptococcus gattii), with preliminary evidence that varieties neoformans and grubii can also be distinguished, non-invasive diagnosis of cerebral cryptococcomas, and, in cases of meningitis, monitoring therapeutic response by analysis of cerebrospinal fluid. [source] Themes of liver transplantation,HEPATOLOGY, Issue 6 2010Thomas E. Starzl Liver transplantation was the product of five interlocking themes. These began in 1958-1959 with canine studies of then theoretical hepatotrophic molecules in portal venous blood (Theme I) and with the contemporaneous parallel development of liver and multivisceral transplant models (Theme II). Further Theme I investigations showed that insulin was the principal, although not the only, portal hepatotrophic factor. In addition to resolving long-standing controversies about the pathophysiology of portacaval shunt, the hepatotrophic studies blazed new trails in the regulation of liver size, function, and regeneration. They also targeted inborn metabolic errors (e.g., familial hyperlipoproteinemia) whose palliation by portal diversion presaged definitive correction with liver replacement. Clinical use of the Theme II transplant models depended on multiple drug immunosuppression (Theme III, Immunology), guided by an empirical algorithm of pattern recognition and therapeutic response. Successful liver replacement was first accomplished in 1967 with azathioprine, prednisone, and antilymphoid globulin. With this regimen, the world's longest surviving liver recipient is now 40 years postoperative. Incremental improvements in survival outcome occurred (Theme IV) when azathioprine was replaced by cyclosporine (1979), which was replaced in turn by tacrolimus (1989). However, the biologic meaning of alloengraftment remained enigmatic until multilineage donor leukocyte microchimerism was discovered in 1992 in long-surviving organ recipients. Seminal mechanisms were then identified (clonal exhaustion-deletion and immune ignorance) that linked organ engraftment and the acquired tolerance of bone marrow transplantation and eventually clarified the relationship of transplantation immunology to the immunology of infections, neoplasms, and autoimmune disorders. With this insight, better strategies of immunosuppression have evolved. As liver and other kinds of organ transplantation became accepted as healthcare standards, the ethical, legal, equity, and the other humanism issues of Theme V have been resolved less conclusively than the medical-scientific problems of Themes I-IV. HEPATOLOGY 2010 [source] A new oral delivery system for 5-ASA: Preliminary clinical findings for MMxINFLAMMATORY BOWEL DISEASES, Issue 5 2005Cosimo Prantera MD Abstract Background: Multi-matrix (MMx), a new delivery system for mesalazine, seems to release 5-aminosalicyclic acid (5-ASA) preferentially in the sigmoid colon. This study had 2 objectives: (1) to evaluate the therapeutic response to MMx in patients with active left-sided disease and (2) to gain additional insights as to how the therapy would compare with topical 5-ASA. Methods: Patients received either 1.2 g of 5-ASA MMx three times per day plus placebo enema or 4 g of 5-ASA enema plus placebo tablets for 8 weeks. The primary endpoint was clinical remission (clinical activity index ,4) at 8 weeks. Secondary endpoints were endoscopic and histologic remissions. Results: Seventy-nine patients were enrolled. Clinical remission rates at 4 and 8 weeks were 57.5% and 60.0% for patients treated with MMx and 68.4% and 50.0% for patients randomized to 5-ASA enemas, respectively (95% confidence interval for the difference at 8 weeks, ,12 to +32). Endoscopic remission was achieved by 45.0% of patients on 5-ASA MMx and by 36.8% of those on enema, whereas 15.0% and 8% of patients, respectively, showed histologic remission. Compliance was 97.0% for oral and 87.5% for topical therapy. In the enema group, compliance was 88.0% for the patients in remission and 65.5% for those with active disease. Conclusions: Preliminary studies suggest that similar rates for induction of remission can be expected from 5-ASA enemas and MMx for patients with left-sided ulcerative colitis. [source] Efficacy, safety and tolerability of lumiracoxib in patients with rheumatoid arthritisINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2004P. Geusens Summary A randomised, double-blind study was performed to assess the efficacy and tolerability of lumiracoxib in patients with rheumatoid arthritis (RA). Patients received lumiracoxib 200 mg once daily (o.d.) (n = 280), lumiracoxib 400 mg o.d. (n = 281), naproxen 500 mg twice daily (n = 279) or placebo (n = 284) for 26 weeks. The primary efficacy variable was response to treatment according to ACR20 criteria (adjusted for prohibited concomitant or excessive rescue medication use and discontinuations due to unsatisfactory therapeutic response) at week 13. Safety and tolerability was also assessed. Significantly more patients receiving lumiracoxib than placebo were responders according to ACR20 criteria at week 13 (41.1 and 42.7% for lumiracoxib 200 and 400 mg o.d., respectively; 32.4% for placebo; both p < 0.05). The proportion responding to naproxen (39.1%) was not significantly different from placebo. Prespecified gastrointestinal adverse events were more frequent with naproxen than with either lumiracoxib dose or placebo. Lumiracoxib is therefore an effective and well-tolerated therapy for RA. [source] Presence of Leishmania organisms in specific and non-specific skin lesions in HIV-infected individuals with visceral leishmaniasisINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2002Ricardo J. Bosch MD BackgroundLeishmania coinfection is frequently seen in human immunodeficiency virus (HIV)-infected patients in endemic areas, and from time to time the protozoan is detected in cutaneous biopsies. Objective To establish the characteristics and possible ethiologic role of the presence of Leishmania in these lesions. Methods We studied 12 cutaneous biopsies with Leishmania organisms from nine HIV-infected patients (seven men and two women) with visceral leishmaniasis, diagnosed by bone marrow examination, seen over a period of 9 years. Results Based on clinical characteristics, evolution and response to anti-leishmanial treatment, cutaneous alterations were found to be related to the presence of the protozoan in six cases, whereas in the other six cases it was not considered responsible for the dermatological lesions (dermatofibroma, and lesions of psoriasis, Reiter's syndrome, bacillary angiomatosis, cryptococcosis and oral aphthae). Of note was the high prevalence of specific mucocutaneous manifestations, usually accompanied by intense pruritus, great variability, and a tendency to relapse after treatment stopped. On two occasions, detection of the protozoa in skin biopsies led to the diagnosis of a previously unsuspected visceral leishmaniasis. Conclusions Cutaneous detection of Leishmania is frequent in HIV-infected individuals with visceral leishmaniasis. Sometimes Leishmania is associated with changes attributable to other dermatological processes, and its presence does not imply a causative role. A clear relationship between the systemic process and the therapeutic response is necessary to demonstrate an ethiologic role. [source] Once-daily desloratadine improves the signs and symptoms of chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled studyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 1 2001Johannes Ring MD Background Chronic idiopathic urticaria (CIU) is the most common type of chronic urticaria, and pruritus is the most prominent symptom. Antihistamines are the first-line treatment for CIU. Sedation and anticholinergic adverse effects are often experienced with the first-generation antihistamines and there is a risk of cardiovascular adverse effects and drug interactions with some second-generation agents. Hence, new treatment options are needed. Desloratadine is a new, potent, nonsedating antihistamine that has an excellent cardiovascular safety profile. Methods This was a multicenter, randomized, double-blind, placebo-controlled study designed to determine the efficacy and safety of desloratadine in the treatment of moderate-to-severe CIU. A total of 190 patients, aged 12,79 years, with at least a 6-week history of CIU and who were currently experiencing a flare of at least moderate severity, were randomly assigned to therapy with desloratadine 5 mg or placebo once daily for 6 weeks. Twice daily, patients rated the severity of CIU symptoms (pruritus, number of hives, and size of largest hive), as well as the impact of CIU symptoms on sleep and daily activity. Patients and investigators jointly evaluated therapeutic response and overall condition. Safety evaluations included the incidence of treatment-emergent adverse events, discontinuations due to adverse events, and changes from baseline in vital signs, laboratory parameters, and ECG intervals. Results Desloratadine was superior to placebo in controlling pruritus and total symptoms after the first dose and maintained this superiority to the end of the study. Measures of sleep, daily activity, therapeutic response, and global CIU status were also significantly better with desloratadine after the first dose; these clinical benefits were also maintained throughout the 6-week study. No significant adverse events occured. Conclusions Desloratadine 5 mg daily is a safe and effective treatment for CIU with significant benefits within 24 h and maintained through the treatment period. [source] Is there variability in drug release and physical characteristics of amiodarone chloride from different commercially available tablets?INTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 4 2010Possible therapeutic implications Abstract Objectives, Amiodarone is a low-solubility, high-permeability drug with a narrow therapeutic index and reported bioavailability problems associated with switching formulations. The aim of this study was to identify whether there is variability in drug release and physical characteristics of different commercially available amiodarone hydrochloride formulations in Australia. Methods, Four available formulations (innovator Cordarone (COR) and generic products G1, G2 and G3) were tested for drug dissolution, content uniformity, hardness, weight variation, friability and disintegration in accordance with the US Pharmacopeia specifications. Key findings, The tested formulations exhibited variable dissolution behaviours: G1 and G3 exhibited the fastest dissolution, G2 dissolution was the slowest and Cordarone showed a medium dissolution. After 3 months' exposure to high temperature (40 ± 2°C) and relative humidity (75 ± 5%), the products exhibited a higher degree of disparity, with drug-release profiles of the generics being markedly different from that of Cordarone. This suggests possible implications on bioequivalence for patients who live in warm/tropical regional areas. Most products met the US Pharmacopeia specifications for drug-content uniformity and other test physical characteristics. Conclusions, The results suggested that variability in drug release profiles in vitro of amiodarone formulations might be a potential indicator of compromised bioavailability, causing possible interference with the therapeutic response of the drug. [source] Restriction of dietary calories, fat and iron improves non-alcoholic fatty liver diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2007Mika Yamamoto Abstract Background:, The pathogenesis of non-alcoholic steatohepatitis (NASH) is unclear. Recent studies suggested that oxidative stress plays an important role in the mechanism of NASH. Excessive accumulation of iron in the liver causes oxidative stress. The aim of the present study was to evaluate the grade of hepatic iron accumulation and the therapeutic response to restriction of calories, fat and iron in patients with non-alcoholic fatty liver disease (NAFLD). Methods:, Twenty-seven NAFLD patients were enrolled. The patients were categorized into two groups: 17 patients with NASH and 10 with simple steatosis. Twelve NAFLD patients (NASH, n = 9; simple steatosis, n = 3) were given a dietary prescription including restriction of energy, fat and iron. Results:, Positive iron staining was observed in 71% and 50% of patients with NASH and simple steatosis, respectively. The average energy intake, fat energy fraction and iron intake decreased significantly 6 months after the beginning of the diet in all patients. In addition, the levels of serum transaminase and ferritin were significantly decreased. Conclusion:, Dietary restriction of calories, fat and iron improved NAFLD. Reduced serum ferritin levels appear to reduce oxidative stress in the liver. [source] Bridging the gap between evidence and practice in acute decompensated heart failure managementJOURNAL OF HOSPITAL MEDICINE, Issue S6 2008FACP, Franklin A. Michota Jr MD Abstract Registry data indicate a gap between evidence-based guidelines and current management of patients with acute decompensated heart failure (ADHF). Bridging this gap is crucial given the frequency and cost of hospitalization for this disorder. Patients with ADHF require rapid assessment to determine appropriate treatment location and initial therapy. Patients with impending respiratory failure or cardiogenic shock should be managed in an intensive care setting, patients with congestion that is expected to require prolonged intravenous therapy should be admitted to the hospital, and patients with congestion that is likely to respond within 12,24 hours can be managed in an observation unit. Clinical status should guide selection of initial therapy. Initially, therapeutic response should be assessed every couple of hours. Once effective acute therapy has been established, it is important to implement strategies to improve long-term outcomes. These strategies include ensuring that care complies with established core performance measures, providing patient education in a manner suited to ensure comprehension and retention, and arranging for appropriate outpatient follow-up, ideally in a comprehensive heart failure disease management program. The purpose of this review is (1) to examine evidence-based guidelines for the treatment of ADHF, (2) to present a practical algorithm for patient assessment and treatment derived from these guidelines and personal experience, and (3) to discuss systems to enhance the ultimate transition of patient care from the inpatient to outpatient setting. Journal of Hospital Medicine 2008;3(Suppl 6):S7,S15. ©2008 Society of Hospital Medicine. [source] Interferon-, therapy: Evaluation of routes of administration and delivery systemsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2002Husam M. Younes Abstract Although different routes and delivery systems have been used to deliver interferon-, (IFN-,) for the treatment of a variety of viral and neoplastic diseases, little has been reported regarding the most efficient and least toxic routes and drug delivery modes required to achieve these goals. To have a greater understanding of the best strategies to use to administer this cytokine in an efficient, stable, and safe manner, this review details aspects of IFN-, concerning its mechanism of action, physical properties, and pharmacokinetics. One important conclusion that is drawn from this analysis is that a consistent, local concentration of IFN-, is necessary to achieve an optimal therapeutic response. A critical discussion covering the advantages and limitations of the currently used methodologies to deliver IFN-, in such a fashion is presented. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2,17, 2002 [source] Serum 6-Beta-Naltrexol Levels Are Related to Alcohol Responses in Heavy DrinkersALCOHOLISM, Issue 9 2000Mary E. McCaul Background: There is strong evidence for the role of the endogenous opioid system in alcohol reinforcement and consumption; however, recent human laboratory studies and clinical trials have reported mixed effects of naltrexone (a nonselective opioid antagonist) on alcohol-related behaviors. This paper reports a secondary data analysis of a human laboratory study that examines the relationship between serum levels of 6-beta-naltrexol, the major, biologically active metabolite of naltrexone, and subjective effects of alcohol. Methods: The study used a within-subjects design to examine the effects of naltrexone (0, 50, and 100 mg/day) on subjective responses to alcohol (none, moderate, and high dose) in heavy drinkers (n= 23). Each subject received three doses of naltrexone in random order; each naltrexone dose was administered over an 8 day period on an inpatient unit, with a 1 week outpatient washout between doses. After stabilization at each of the naltrexone doses, subjects participated in three alcohol challenge sessions (none, moderate, and high dose) in random order; thus, each subject participated in a total of nine alcohol administration sessions. Results: Doubling the naltrexone dose (50 vs. 100 mg/day) doubled the mean serum 6-beta-naltrexol levels. At each naltrexone dose, there was a 4-fold range in 6-beta-naltrexol levels across subjects. Before alcohol administration, higher 6-beta-naltrexol levels were associated with higher ratings of sedation. After high-dose alcohol administration, higher 6-beta-naltrexol levels were associated with significantly lower ratings of liking and best effects. Conclusions: These findings provide further evidence of the involvement of the opioid system in the modulation of alcohol effects and suggest that serum 6-beta-naltrexol concentrations may be important in predicting therapeutic response to naltrexone. [source] Circumscribed palmar hypokeratosis: clinical evolution and ultrastructural study after prolonged treatment with topical calcipotriolJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2005F Urbina Abstract Circumscribed palmar hypokeratosis is a recently described condition that consists of a solitary area of depressed skin affecting the palm (or sole). Its histopathological features include a thinned horny layer, a slightly diminished granular cell layer, and intraepidermal vacuolated cells. Prolonged treatment with topical calcipotriol resulted in complete recovery of the affected zone in the case reported here. A second biopsy of the lesion taken at around the fourth year of therapy showed a normalization of the granular layer, a reduction in the intraepidermal vacuolated cells, and a somewhat thicker horny layer. An ultrastructural study carried out at the same time showed a reduction in keratin bundles and keratohyalin granules, and an increase in lipid droplets up to the horny layer. These findings and the therapeutic response to topical calcipotriol support the concept that circumscribed palmar hypokeratosis is a focalized abnormal keratinization defect morphologically expressed at the granular and horny layers. [source] Towards predicting the therapeutic response in patients with hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010C. Féray No abstract is available for this article. [source] Towards predicting the therapeutic response in patients with hepatitis C: authors' replyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2010F. Angelico No abstract is available for this article. [source] Magnetic Resonance Imaging and Histological Classification of Intracranial Meningiomas in 112 DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2008B.K. Sturges Background: Intracranial meningiomas are the most common primary brain tumors in dogs. Classification of meningiomas by tumor grade and subtype has not been reported, and the value of magnetic resonance imaging (MRI) characteristics for predicting tumor subtype and grade has not been investigated. Hypothesis: Canine intracranial meningiomas are a heterogenous group of tumors with differing histological subtypes and grades. Prediction of histopathological classification is possible based on MRI characteristics. Animals: One hundred and twelve dogs with a histological diagnosis of intracranial meningioma. Methods: Retrospective observational study. Results: Meningiomas were overrepresented in the Golden Retriever and Boxer breeds with no sex predilection. The incidence of specific tumor grades was 56% benign (Grade I), 43% atypical (Grade II), and 1% malignant (Grade III). Grade I histological subtypes included meningothelial (43%), transitional (40%), microcystic (8%), psammomatous (6%), and angiomatous (3%). No statistically significant (P < .05) associations were found among tumor subtype or grade and any of the MRI features studied. Conclusions and Clinical Importance: Meningiomas in dogs differ from their counterparts in humans mainly in their higher incidence of atypical (Grade II) tumors observed. MRI characteristics do not allow for prediction of meningioma subtype or grade, emphasizing the necessity of histopathology for antemortem diagnosis. The higher incidence of atypical tumors in dogs may contribute to the poorer therapeutic response in dogs with meningiomas as compared with the response in humans with meningiomas. [source] Usefulness of contrast-enhanced ultrasonography with abdominal virtual ultrasonography in assessing therapeutic response in hepatocellular carcinoma treated with radiofrequency ablationLIVER INTERNATIONAL, Issue 10 2006Yoshiyasu Kisaka Abstract: Objective: Contrast-enhanced computed tomography (CECT) is regarded as the gold standard for assessing the efficacy of radiofrequency ablation (RFA) against hepatocellular carcinoma (HCC). We evaluated the efficacy of virtual ultrasonography (VUS) with contrast-enhanced ultrasonography (CEUS) vs. CECT for assessing the response to RFA. Materials and methods: Study 1: The therapeutic responses in 22 patients with 26 HCC nodules were assessed by CEUS with VUS as well as by CECT. The efficacy of treatment was based on whether the safety margin was greater than 5 mm after RFA. Study 2: In seven patients with seven HCC nodules, the nodules were treated by RFA and the therapeutic efficacy was assessed by CEUS with VUS. The number of RFA sessions was assessed. Results: Compared with CECT, CEUS with VUS had a specificity of 77%, a sensitivity of 91.6%, and an accuracy of 84%. When the therapeutic response to RFA was analyzed by CECT only, 1.86±0.69 assessments (mean) were required, while when response was assessed by CEUS with VUS, 1.14±0.38 CECT assessments were required (P=0.03). Conclusion: CEUS with VUS is effective in assessing the therapeutic response to RFA of HCC. Moreover, the number of CECT scans required is reduced by this approach. [source] Increased circulating and intrahepatic T-cell-specific chemokines in chronic hepatitis C: relationship with the type of virological response to peginterferon plus ribavirin combination therapyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2004A. Apolinario Summary Aims :,To determine the serum and intrahepatic levels of T-helper-1-associated chemokines in patients with chronic hepatitis C before, during and after peginterferon plus ribavirin combination therapy and to search for correlations with baseline characteristics of hepatitis C virus-related chronic liver disease and type of therapeutic response. Methods :,Serum chemokine levels were determined by enzyme-linked immunosorbent assays and intrahepatic chemokine messenger RNA and protein levels were tested by ribonuclease protection assay and immunohistochemistry. Results :,Serum and intrahepatic chemokine levels were elevated in all patients with chronic hepatitis C and showed a marked decrease in patients who obtained a virological response vs. non-responders. Increased serum interferon-,-inducible protein-10 levels at baseline in genotype 1-infected patients were significantly associated with greater degrees of intrahepatic inflammation and fibrosis (P = 0.0046 and P = 0.02, respectively) and with virological non-response (P = 0.01). In patients with genotype 1, basal serum interferon-,-inducible protein-10 levels greater than 299 pg/mL identified 80% of non-responders and lower than 299 pg/mL identified 63% of responders. Conclusions :,Circulating and intrahepatic T-helper-1-associated chemokines are abnormally elevated in patients with chronic hepatitis C. Increased baseline serum interferon-,-inducible protein-10 levels in genotype 1-infected patients are associated with virological non-response to peginterferon plus ribavirin combination therapy. [source] Health-related quality of life among persons with irritable bowel syndrome: a systematic reviewALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2002H. B. El-Serag Summary Aim : To perform a systematic review of the literature with three objectives: (1) to compare the health related quality of life (HRQoL) of patients with irritable bowel syndrome with that of healthy controls; (2) to compare the HRQoL of irritable bowel syndrome patients to those with other diseases; and (3) to examine therapy-associated changes in HRQoL of irritable bowel syndrome patients. Methods : Searches of all English and non-English articles from 1980 to 2001 were performed in Medline and Embase, and two investigators performed independent data abstraction. Results : Seventeen articles met our selection criteria. 13 studies addressed objective no. 1; 11 showed a significant reduction in HRQoL among irritable bowel syndrome patients. Of these, only one study was considered of high quality. Four studies addressed objective no. 2, none of which was considered to be high quality in addressing this objective. Four trials (three of high quality) addressed objective no. 3. One showed that symptomatic improvement with Leupron compared to placebo was accompanied an improvement only in the comparative health domain of the HRQoL. The second study reported significant positive changes in HRQoL after 12 weeks of cognitive behavioural therapy. The third report of two placebo-controlled studies indicated significant improvement with alosetron on most domains of Irritable Bowel Syndrome Quality of Life Questionnaire. Conclusions : (i) There is reasonable evidence for a decrease in HRQoL in patients with moderate to severe irritable bowel syndrome; however, the data are conflicting regarding the impact of irritable bowel syndrome on HRQoL in population-based studies of nonconsulters. (ii) HRQoL in irritable bowel syndrome patients is impaired to a degree comparable to other chronic disorders such as GERD and depression. (iii) A therapeutic response in irritable bowel syndrome-related pain has a corresponding improvement in HRQoL. (iv) Limitations of the literature include focusing on moderate-severe irritable bowel syndrome in referral centres, and lack of appropriate controls [source] Efficacy and safety of oral ridogrel in the treatment of ulcerative colitis: two multicentre, randomized, double-blind studiesALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2002G. N. J. Tytgat Background: Ridogrel at low doses inhibits thromboxane synthase. Oral ridogrel, from 5 mg once daily to 150 mg twice daily, improves the endoscopic appearance of colonic mucosa and clinical manifestations in mild to moderate ulcerative colitis. Aim: One US trial and one international trial were conducted to determine the effect of ridogrel on mild to severe active ulcerative colitis. Methods: Two 12-week, double-blind, randomized, parallel-group trials were conducted. A US trial compared 0.5 mg, 2.5 mg and 5 mg of ridogrel once daily with placebo. An international trial compared 0.5 mg of ridogrel once daily with 2.5 mg and 5.0 mg of ridogrel once daily and 800 mg of mesalazine (known as mesalamine in the USA) three times daily. The primary efficacy outcome measure was the rate of complete remission. Results: In the US trial, complete remission was achieved in 20.8% of patients in the 0.5 mg ridogrel group, 17.9% in the 2.5 mg ridogrel group, 20.6% in the 5.0 mg ridogrel group and 13.6% in the placebo group. In the international trial, 14.4% of patients in the 0.5 mg ridogrel group, 19.6% in the 2.5 mg ridogrel group, 19.4% in the 5.0 mg ridogrel group and 16.4% in the mesalazine group experienced complete remission. In the international trial, rates of complete remission at the end-point were greater in the 2.5 mg and 5.0 mg ridogrel groups than in the 0.5 mg ridogrel group, but the differences were not statistically significant. In the US trial, rates of complete remission at the end-point were greater in the 2.5 mg and 5.0 mg ridogrel groups than in the placebo group, but the differences were not statistically significant. Approximately 30% of the patients in each group discontinued treatment before the 12-week end-point owing to a lack of therapeutic response. All doses of ridogrel were well tolerated and comparable with placebo or mesalazine in terms of safety. Conclusions: No significant differences in the primary efficacy outcome measure were found between either the 2.5 mg or the 5.0 mg dose of ridogrel and placebo in the US trial and between either the 2.5 mg or the 5.0 mg dose of ridogrel and the 0.5 mg dose of ridogrel, a surrogate dose for placebo, in the international trial. There was no clear indication in either trial of an effective dose of ridogrel in the treatment of ulcerative colitis. [source] Efficacy of desloratadine in intermittent allergic rhinitis: a GA2LEN studyALLERGY, Issue 10 2009J. Bousquet Background:, The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines proposed a classification for allergic rhinitis based on the duration of symptoms (intermittent, persistent) rather than on the time of allergen exposure (seasonal, perennial). There is no placebo-controlled, randomized clinical trial on intermittent allergic rhinitis (IAR) to date. Desloratadine (DL) is recommended for the first-line treatment of seasonal and perennial allergic rhinitis. Objectives:, To assess the efficacy and safety of DL in subjects with IAR based on the ARIA classification. Methods:, Patients over 12 years of age with IAR were assessed over 15 days of treatment with DL 5 mg once daily (n = 276) or placebo (n = 271). The primary endpoint was the AM/PM reflective total 5 symptom score (T5SS). Secondary endpoints included AM/PM instantaneous T5SS and individual symptoms, therapeutic response, symptom severity by visual analogue scale, and quality-of-life. Results:, The mean reduction of AM/PM reflective T5SS was significantly greater with DL than with placebo over 15 days (,3.01 vs,2.13, P < 0.001) and on each individual day (P < 0.05). Mean AM instantaneous T5SS was reduced significantly with DL compared to placebo as early as day 2 (,1.84 vs,0.89; P < 0.001). The therapeutic response and improvement in quality-of-life were significantly greater with DL than with placebo (P < 0.001 for each). The frequency of treatment-related adverse events was low and similar between DL (7.2%) and placebo (7.0%). Conclusions:, This is the first large trial to show that treatment can be effective in IAR. Desloratadine was effective and safe. [source] Analysis of the course of Parkinson's disease under dopaminergic therapy: Performance of "fast tapping" is not a suitable parameterMOVEMENT DISORDERS, Issue 3 2005Peter H. Kraus MD Abstract In addition to clinical rating scales, instrumental methods are employed frequently for assessment of performance or motor deficits in Parkinson's disease (PD). Many studies have analyzed such parameters in cross-sectional studies. We employed a battery of tests to investigate fine motor performance over a period of 4 years in 411 de novo parkinsonian patients from the Prado study. Specifically, tapping and pegboard testing ("plugging") were evaluated and performance on these tests compared with clinical ratings. Plugging scores correlated well with tapping scores and clinical rating at each assessment timepoint. Both tests also showed significant differences to healthy controls. Nevertheless "fast tapping" was found to be less impaired than was plugging in de novo patients. Over time, it was observed that plugging scores, but not tapping scores, exhibited changes that paralleled movements in clinical score. Plugging scores exhibited a marked response to dopaminergic therapy whereas fast tapping showed no therapeutic response. Fast tapping is certainly not suitable for assessment of bradykinesia or hypokinesia, and does not respond to dopaminergic therapy. © 2004 Movement Disorder Society [source] | ||||||||||||||||||||||||||||||||||||||||