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Concomitant Treatment (concomitant + treatment)
Selected AbstractsBotulinum-A Toxin Treatment of the Lower Eyelid Improves Infraorbital Rhytides and Widens the EyeDERMATOLOGIC SURGERY, Issue 8 2001Timothy Corcoran Flynn MD Botulinum-A exotoxin (BTX-A) can be used cosmetically to improve rhytides, particularly of the upper one-third of the face. In this study, fifteen women had BTX-A (BOTOX, Allergan, Inc.) injected into the orbicularis oculi muscle. One lower eyelid received two units just subdermally in the midpupillary line three millimeters below the ciliary margin. The opposite periocular area received two units BTX-A in the lower eyelid with 12 units BTX-A injected into the lateral orbital ("crow's foot") area. Three injections of four units each were placed 1.5 cm from the lateral canthus, each 1 cm apart. Patients and physicians independently evaluated the degree of improvement (grade 0 = no improvement, grade 1 = mild improvement, grade 2 = moderate improvement, and grade 3 = dramatic improvement). An independent photographic analysis was performed. Patients reported a grade of 0.73 when two units were injected alone into the lower lid, and a grade of 1.9 when the lower eyelid and the lateral orbital areas were injected. Physician assessment was grade 0.7 with injection of the eyelid alone and grade 1.8 with injection of the lower eyelid and lateral orbital area. Single investigator photographic analysis demonstrated that 40% of the subjects who had injection of the lower eyelid alone had an increased palpebral aperture (IPA), while 86% of the subjects who had injection of the lower eyelid and lateral orbital area had an IPA. Subjects receiving two units alone had an average 0.5 mm IPA and a mean 1.3 mm IPA at full smile. Concomitant treatment of the lateral orbital area produced a mean 1.8 mm IPA at rest and a mean 2.9 mm IPA at full smile. The results were more notable in the Asian eye. Two units of BTX-A injected into the lower eyelid orbicularis oculi muscle improves infraorbital wrinkles, particularly when used in combination with BTX-A treatment of the lateral orbital area. [source] Accumulation of hydrogen peroxide is an early and crucial step for paclitaxel-induced cancer cell death both in vitro and in vivo,INTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Jérôme Alexandre Abstract Intracellular events following paclitaxel binding to microtubules that lead to cell death remain poorly understood. Because reactive oxygen species (ROS) are involved in the cytotoxicity of anticancer agents acting through independent molecular targets, we explored the role of ROS in paclitaxel cytotoxicity. Within 15 min after in vitro exposure of A549 human lung cancer cells to paclitaxel, a concentration-dependent intracellular increase in O°2, and H2O2 levels was detected by spectrofluorometry. Addition of N -acetylcysteine (NAC) or glutathione, two H2O2 scavenger, induced a 4-fold increase in paclitaxel IC50. Delaying NAC co-incubation by 4 hr, resulted in a 3-fold reduction in cell protection. The glutathione synthesis inhibitor, buthionine sulfoximine significantly increased paclitaxel cytotoxicity and H2O2 accumulation, but did not modify O°2, levels. Co-incubation with diphenylene iodonium suggested that paclitaxel induced-O°2, production was in part associated with increased activity of cytoplasmic NADPH oxidase. Concomitant treatment with inhibitors of caspases 3 and 8 increased cell survival but did not prevent the early accumulation of H2O2. To evaluate the role of ROS in paclitaxel antitumoral activity, mice were injected with LLC1 lung cancer cells and treated with paclitaxel i.p. and/or NAC. The antitumoral activity of paclitaxel in mice was abolished by NAC. In conclusion, the accumulation of H2O2 is an early and crucial step for paclitaxel-induced cancer cell death before the commitment of the cells into apoptosis. These results suggest that ROS participate in vitro and in vivo to paclitaxel cytotoxicity. © 2006 Wiley-Liss, Inc. [source] Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive ratsPHYTOTHERAPY RESEARCH, Issue 5 2007Mahmoud M. Khattab Abstract The present study was undertaken to evaluate the protective effect of thymoquinone (TQ), the main constituent of the volatile oil from Nigellasativa seeds, in rats after chronic inhibition of nitric oxide synthesis with N, -nitro- l -arginine methyl esters (l -NAME). Rats were divided randomly into different treatment groups: control, l -NAME, TQ and l -NAME + TQ. Hypertension was induced by 4 weeks administration of l -NAME (50 mg/kg/day p.o.). TQ was administered alone or in combination with l -NAME and continued for 4 weeks. The animals were killed, and the serum and kidney tissues were isolated for the determination of creatinine and glutathione (GSH), respectively. Rats receiving l -NAME showed a progressive increase in systolic blood pressure compared with control rats. Concomitant treatment with TQ (0.5 and 1 mg/kg/day p.o.) reduced the increase in systolic blood pressure induced by l -NAME in a dose dependent manner. Kidney injury was demonstrated by a significant increase in serum creatinine and a decrease in GSH in kidney tissue from l -NAME treated rats. Treatment of rats with TQ decreased the elevated creatinine and increased GSH to normal levels. TQ inhibited the in vitro production of superoxide radical in enzymatic and non-enzymatic systems. In conclusion, TQ is effective in protecting rats against l -NAME-induced hypertension and renal damage possibly via antioxidant activity. Copyright © 2007 John Wiley & Sons, Ltd. [source] Golimumab, a new human anti,tumor necrosis factor , antibody, administered intravenously in patients with active rheumatoid arthritis: Forty-eight,week efficacy and safety results of a phase III randomized, double-blind, placebo-controlled study ,ARTHRITIS & RHEUMATISM, Issue 4 2010Joel Kremer Objective To assess the efficacy and safety of intravenous administration of golimumab in patients with rheumatoid arthritis (RA). Methods Adult patients with RA in whom disease activity was persistent despite treatment with methotrexate (MTX) at a dosage of 15,25 mg/week for ,4 weeks were randomized to receive intravenous infusions of placebo plus MTX or intravenous infusions of golimumab at a dose of 2 mg/kg or 4 mg/kg, with or without MTX, every 12 weeks through week 48. Patients with <20% improvement in the swollen and tender joint counts could enter early escape and receive additional active treatment (week 16) or could have their dose regimen adjusted (week 24). The primary end point was the proportion of patients achieving a 50% response according to the American College of Rheumatology improvement criteria (ACR50) at week 14. Results The primary study end point was not met (at week 14, an ACR50 response was observed in 21% of the patients treated with golimumab plus MTX compared with 13% of the patients treated with placebo plus MTX [P = 0.051]). By week 24, significantly more patients treated with golimumab plus MTX had achieved an ACR50 response. Differences in the proportion of patients achieving an ACR50 response between the group receiving golimumab monotherapy and the group receiving placebo plus MTX were not significant at either week 14 (16% versus 13%) or week 24 (10% versus 9%). At week 48, the proportions of patients achieving ACR20 and ACR50 responses were highest among those who had received golimumab 4 mg/kg plus MTX (70% and 48%, respectively). Concomitant treatment with MTX was associated with a lower incidence of antibodies to golimumab. The most commonly reported adverse events through week 48 were infections (48% of patients treated with golimumab with or without MTX and 41% of patients receiving placebo plus MTX). Conclusion The primary end point was not met. However, intravenously administered golimumab plus MTX appears to have benefit in the longer-term reduction of RA signs/symptoms in MTX-resistant patients, with no unexpected safety concerns. [source] DOPAMINE D2 RECEPTOR STIMULATION INHIBITS ANGIOTENSIN II-INDUCED HYPERTROPHY IN CULTURED NEONATAL RAT VENTRICULAR MYOCYTESCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2009Hong Li SUMMARY 1Myocardial hypertrophy is a common pathological change that accompanies cardiovascular disease. Dopamine D2 receptors have been demonstrated in cardiovascular tissues. However, the pathophysiological involvement of D2 receptors in myocardial hypertrophy is unclear. Therefore, the effects of the D2 receptor agonist bromocriptine and the D2 receptor antagonist haloperidol on angiotensin (Ang) II- or endothelin (ET)-1-induced hypertrophy of cultured neonatal rat ventricular myocytes were investigated in the present study. 2Protein content and protein synthesis, determined by examining [3H]-leucine uptake, were used as estimates of cardiomyocyte hypertrophy. The expression of D2 receptor protein in neonatal rat ventricular myocytes was determined using western blotting. Changes in [Ca2+]i in cardiomyocytes were observed by laser scanning confocal microscopy. 3Angiotensin II and ET-1, both at 10 nmol/L, induced myocyte hypertrophy, as demonstrated by increased protein content and synthesis, [Ca2+]i levels, protein kinase C (PKC) activity and phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase and mitogen-activated protein kinase (MAPK) p38 (p38). Concomitant treatment of cells with 10 nmol/L AngII plus 10 µmol/L bromocriptine significantly inhibited cardiomyocyte hypertrophy, MAPK phosphorylation and PKC activity in the membrane, as well as [Ca2+]i signalling pathways, compared with the effects of AngII alone. In addition, 10 µmol/L bromocriptine significantly inhibited cardiomyocyte hypertrophy induced by 10 nmol/L ET-1. However, pretreatment with haloperidol (10 µmol/L) had no significant effects on cardiomyocyte hypertrophy induced by either AngII or ET-1. 4In conclusion, D2 receptor stimulation inhibits AngII-induced hypertrophy of cultured neonatal rat ventricular myocytes via inhibition of MAPK, PKC and [Ca2+]i signalling pathways. [source] Molecular and functional characterization of novel CRFR1 isoforms from the skinFEBS JOURNAL, Issue 13 2004Alexander Pisarchik In our continued studies on corticotropin releasing factor receptor (CRFR1) signaling in the skin, we tested functional activity of CRFR1,, e, f, g and h isoforms after transfection to COS cells. Both membrane-bound and soluble variants are translated in vivo into final protein products that undergo further post-translational modifications. CRFR1, was the only isoform coupled directly to adenylate cyclase with the exception of an artificial isoform (CRFR1h2) with the insertion of 37 amino acids between the ligand binding domain and the first extracellular loop that was capable of producing detectable levels of cyclic AMP (cAMP). Soluble isoforms could modulate cell response with CRFR1e attenuating and CRFR1h amplifying CRFR1,-coupled cAMP production stimulated by urocortin. Testing with plasmids containing the luciferase reporter gene, and inducible cis -elements (CRE, CaRE, SRE, AP1 or NF-,B) demonstrated that only CRFR1, was involved directly in the transcriptional regulation, while CRFR1g inhibited CRE activity. Significantly higher reporter gene expression by CRF was observed than that mediated by 4,-phorbol 12-myristate 13-acetate and forskolin alone, being compatible with the concomitant treatment by phorbol 12-myristate 13-acetate and forskolin. This suggests that both protein kinase A and C can be involved in CRF-dependent signal transduction. [source] Severe Legionella pneumophila pneumonia following infliximab therapy in a patient with Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 8 2009Florian Beigel MD Abstract Background: Immunosuppressive therapy with anti-TNF-, antibodies is effective in patients with inflammatory bowel disease (IBD). However, there is an increased risk for infections associated with this therapy. Methods: Here, we report the case of a 58-year-old patient with Crohn's disease (CD) treated with steroids and azathioprine who developed severe Legionella pneumophila pneumonia after 3 infusions of infliximab. The patient presented at our IBD department with severe active CD complicated by inflammatory small bowel stenoses and entero-enteral fistulas despite long-term high-dose steroid therapy. To achieve steroid tapering and control of disease activity, immunosuppressive therapy with azathioprine was initiated. Due to persistent symptoms, infusion therapy with the anti-TNF-, antibody infliximab was started, subsequently leading to significant clinical improvement. However, after the third infliximab infusion the patient was hospitalized with fever, severe fatigue, and syncope. Results: Laboratory findings and chest X-ray revealed left-sided pneumonia; cultural analysis showed L. pneumophila serogroup 1 leading to respiratory insufficiency, which required mechanical ventilation for 2 weeks in the intensive care unit. After discontinuation of all immunosuppressive agents and immediate antibiotic therapy the patient recovered completely. Conclusions: To our knowledge, this is the third case of L. pneumophila pneumonia in an IBD patient treated with infliximab. Similar to other published cases, concomitant treatment of immunosuppressives and anti-TNF agents is a major risk factor for the development of L. pneumophila infection, which should be ruled out in all cases of pneumonia in patients with such a therapeutic regimen. Appropriate prevention strategies should be provided in these patients. (Inflamm Bowel Dis 2009) [source] Improved Survival of Cardiac Transplantation Candidates with Implantable Cardioverter Defibrillator Therapy:JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2003Role of Beta-Blocker or Amiodarone Treatment Introduction: Survival in patients awaiting cardiac transplantation is poor due to the severity of left ventricular dysfunction and the susceptibility to ventricular arrhythmia. The potential role of implantable cardioverter defibrillators (ICDs) in this group of patients has been the subject of increasing interest. The aims of this study were to ascertain whether ICDs improve the survival rate of patients on the waiting list for cardiac transplantation and whether any improvement is independent of concomitant beta-blocker or amiodarone therapy. Methods and Results: Data comprised findings from 310 consecutive patients at a single center who were evaluated and deemed suitable for cardiac transplantation and placed on the waiting list. Kaplan-Meier actuarial approach was used for survival analysis. Survival analysis censored patients at time of transplantation or death. Of the 310 patients, 111 (35.8%) underwent successful cardiac transplantation and 164 (52.9%) died while waiting; 35 patients remain on the waiting list. Fifty-nine (19%) patients had ICD placement for ventricular arrhythmias prior to or after being listed. Twenty-nine (49.1%) ICD patients survived until cardiac transplantation, 13 (22%) patients died, and 17 (28.8%) remain on the waiting list. Among non-ICD patients, 82 (32.7%) received transplants, 151 (60.2%) died, and 18 (7.2%) remain on the waiting list. Survival rates at 6 months and 1, 2, 3, and 4 years were better for all ICD patients compared to non-ICD patients (log-rankx2, P = 0.0001). By multivariate analysis, ICD therapy and beta-blocker treatment were the strongest predictors of survival. Further, ICD treatment was associated with improved survival independent of concomitant treatment with beta-blocker or amiodarone. Among ICD and non-ICD patients treated with a beta-blocker or amiodarone, survivals at the 1 and 4 years were 93% vs 69% and 57% vs 32%, respectively (log-rankx2, P = 0.003). Conclusion: ICD therapy is associated with improved survival in high-risk cardiac transplant candidates, and ICD benefit appears to be independent of concomitant treatment. (J Cardiovasc Electrophysiol, Vol. 14, pp. 578-583, June 2003) [source] Activation of extracellular signal-regulated kinases potentiates hemin toxicity in astrocyte culturesJOURNAL OF NEUROCHEMISTRY, Issue 3 2001Raymond F. Regan Hemin is present in intracranial hematomas in high micromolar concentrations and is a potent, lipophilic oxidant. Growing evidence suggests that heme-mediated injury may contribute to the pathogenesis of CNS hemorrhage. Extracellular signal-regulated kinases (ERKs) are activated by oxidants in some cell types, and may alter cellular vulnerability to oxidative stress. In this study, the effect of hemin on ERK activation was investigated in cultured murine cortical astrocytes, and the consequence of this activation on cell viability was quantified. Hemin was rapidly taken up by astrocytes, and generated reactive oxygen species (ROS) within 30 min. Increased immunoreactivity of dually phosphorylated ERK1/2 was observed in hemin-treated cultures at 30,120 min, without change in total ERK. Surprisingly, ERK activation was not attenuated by concomitant treatment with antioxidants (U74500A or 1,10-phenanthroline) at concentrations that blocked ROS generation. Cell death commenced after 2 h of hemin exposure and was reduced by antioxidants and by the caspase inhibitor Z-VAD-FMK. Cytotoxicity was also attenuated by MEK inhibition with PD98059 or U0126 at concentrations that were sufficient to prevent ERK activation. Whereas the effect of Z-VAD-FMK on cell survival was transient, the effect of MEK inhibitors was long-lasting. MEK inhibitors had no effect on cellular hemin uptake or subsequent ROS generation. The present results suggest that hemin activates ERK in astrocytes via a mechanism that is independent of ROS generation. This activation sensitizes astrocytes to hemin-mediated oxidative injury. [source] Thrombin generation in acute coronary syndrome and stable coronary artery disease: dependence on plasma factor compositionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 1 2008K. BRUMMEL-ZIEDINS Summary.,Background:,Acute coronary syndrome (ACS) is associated with thrombin formation, triggered by ruptured or eroded coronary atheroma. We investigated whether thrombin generation based on circulating coagulation protein levels, could distinguish between acute and stable coronary artery disease (CAD). Methods and results:,Plasma coagulation factor (F) compositions from 28 patients with ACS were obtained after onset of chest pain. Similar data were obtained from 25 age- and sex-matched patients with stable CAD. All individuals took aspirin. Patients on anticoagulant therapy were excluded. The groups were similar in demographic characteristics, comorbidities and concomitant treatment. Using each individual's coagulation protein composition, tissue factor (TF) initiated thrombin generation was assessed both computationally and empirically. TF pathway inhibitor (TFPI), antithrombin (AT), factor II (FII) and FVIII differed significantly (P < 0.01) between the groups, with levels of FII, FVIII and TFPI higher and AT lower in ACS patients. When thrombin generation profiles from individuals in each group were compared, simulated maximum thrombin levels (P < 0.01) and rates (P < 0.01) were 50% higher with ACS while the initiation phases of thrombin generation were shorter. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model. The differences between the thrombin generation profiles for each population were primarily dependent upon the collective contribution of AT, FII and FVIII. Conclusion:,Simulations of thrombin formation based on plasma composition can discriminate between acute and stable CAD. [source] Placebo-controlled, double-blind dose-finding study of entacapone in fluctuating parkinsonian patients,MOVEMENT DISORDERS, Issue 1 2007Yoshikuni Mizuno MD Abstract We conducted a multicenter randomized, placebo-controlled double-blind parallel-group study in Japanese Parkinson's disease (PD) patients with wearing-off motor fluctuations to determine the clinical efficacy and safety of entacapone as an adjunct to concomitant treatment with levodopa and a dopa decarboxylase inhibitor (DCI). We randomized 341 patients to receive entacapone 100 or 200 mg or placebo per dose of levodopa/DCI for 8 weeks. The primary efficacy variable was on time change while awake, determined by patients' diaries. Mean baseline on time in each group was approximately 8 hours. Mean on time change at final assessment was 1.4 hours each for entacapone 100-mg and 200-mg groups and by 0.5 hours for the placebo group (P < 0.05). The two entacapone doses were equally efficacious. Adverse events occurred in 79 patients (69.9%) in placebo, 82 (72.6%) in 100 mg, and 98 (86.0%) in 200 mg. The most common adverse event with entacapone was an increase in dyskinesias. The overall safety profile was satisfactory in both entacapone groups. In conclusion, both entacapone 100 and 200 mg were equally effective in increasing on time of PD patients with wearing-off fluctuations, although the safety and tolerability profile appeared more favorable for the 100-mg dose. © 2006 Movement Disorder Society [source] Temporary Disturbances of the QT Interval Precede the Onset of Ventricular Tachyarrhythmias in Patients with Structural Heart DiseasesPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 10 2002BJÖRN HENRIK DIEM DIEM, B.H. et al.: Temporary Disturbances of the QT Interval Precede the Onset of Ventricular Tach-yarrhythmias in Patients with Structural Heart Diseases. An increase in sinus rate prior to ventricular tachyarrhythmias has been demonstrated in previous studies. There is no clear data available concerning changes in ventricular de- and repolarization prior to ventricular tachyarrhythmias, especially in patients with structural heart disease. Therefore, the aim of this study was to analyze the QT and QTc interval (Bazett's formula immediately before the onset of ventricular tachyarrhythmias in stored electrograms of patients with ICDs. The study analyzed 228 spontaneous ventricular tachyarrhythmia episodes in 52 patients (mean age 64 ± 10 years, 49 men, 3 women) and compared them with 146 electrograms of baseline rhythm recorded during regular ICD follow-up. Mean ventricular cycle length (CL), QT interval, and QTc were measured before the onset of ventricular tachyarrhythmia and during baseline rhythm. Prior to ventricular tachyarrhythmias onset, CL was significantly shorter than during baseline rhythm (714 ± 139 vs 828 ± 149 ms, P < 0.0001). By contrast, the QT interval (430 ± 67 ms) and QTc interval (518 ± 67 ms) were significantly prolonged before the onset of ventricular tachyarrhythmias as compared to baseline rhythm (QT 406 ± 67 ms, QTc 450 ± 61 ms; P < 0.0001). CL, QT, and QTc changes were independent of concomitant treatment with antiarrhythmic drugs. Ventricular tachyarrhythmias are preceded by a significant prolongation of the QT and QTc intervals. This phenomenon may represent a greater than normal disparity of repolarization recovery times possibly facilitating the development of ventricular tachyarrhythmias. [source] Effect of Maternal Lead Exposure on Craniofacial Ossification in Rat Fetuses and the Role of Antioxidant TherapyANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2009H. A. Saleh Summary Lead exposure during intrauterine life was found to result in reduced birth weight, impaired skeletal development and post-natal neurotoxic effects. In this study, the effect of pre-natal exposure to different doses of lead on the development of craniofacial skeleton in rat fetuses was investigated. Vitamin E was tested as a concomitant treatment, aiming to improve the fetotoxic effects of lead. Positively pregnant female rats were randomly divided into four groups; groups I and II (L250 and L500), exposed to lead acetate in doses of 250 and 500 mg/l respectively, group III (L500 + E), exposed to lead acetate (500 mg/l) wit concomitant vitamin E and group IV (Control) which was given sodium acetate only. All the treatments started from the first day of gestation till the 20th day, where all rats were sacrificed and the fetuses were recovered. Fetuses were processed to alizarin red staining for ossified components. Twenty-seven bones of the craniofacial skeleton were studied in each fetus where the ossification was scored as being complete, delayed or absent. In all studied fetuses from all groups, changes were found only in eight bones while the remaining craniofacial bones were normally ossified. In affected bones there was a significant decrease in the number of completely ossified bones; associated with a significant increase of both partially ossified and absent bones in L250 and L500 treated groups when compared to the control group. These differences were more significant in the L500 treated group. Giving vitamin E improved the percentage of completely ossified craniofacial bones and decreased the percentage of both partially ossified and absent bones. The most affected bone was presphenoid, then to a lesser extent supraoccipital, squamosal, parietal, interparietal and frontal bone respectively. In conclusion, lead exposure to rats during pregnancy led to varying degrees of fetal growth retardation as well as delayed ossification of some craniofacial bones which were dose dependent and the concomitant supplementation with vitamin E greatly improved the deleterious effect of lead. [source] Mortality in the catastrophic antiphospholipid syndrome: Causes of death and prognostic factors in a series of 250 patientsARTHRITIS & RHEUMATISM, Issue 8 2006Silvia Bucciarelli Objective To assess the main causes of death and the prognostic factors that influence mortality in patients with the catastrophic antiphospholipid syndrome (CAPS). Methods We analyzed the case reports of 250 patients included in the CAPS Registry up to February 2005. To identify prognostic factors for CAPS, we compared the main clinical and immunologic features and the types of treatment in the patients who died with those features in the patients who survived. Results Recovery occurred in 56% of the episodes of CAPS and death occurred in 44%. Cerebral involvement, consisting mainly of stroke, cerebral hemorrhage, and encephalopathy, was considered the main cause of death, being present in 27.2% of patients, followed by cardiac involvement (19.8%) and infection (19.8%). The only factor we identified that was prognostic of a higher mortality rate was the presence of systemic lupus erythematosus (SLE). A higher recovery rate was associated with combined treatment with anticoagulants (ACs) plus corticosteroids (CS) plus plasma exchange (PE) (77.8%), followed by ACs plus CS plus PE and/or intravenous immunoglobulins (69%). In contrast, concomitant treatment with cyclophosphamide did not demonstrate additional benefit. Conclusion Cerebral involvement (mainly consisting of stroke), cardiac involvement, and infections were considered the main causes of death in patients with CAPS. The presence of SLE was related to a higher mortality rate. According to the results of the present study, ACs plus CS plus PE should be the first line of therapy in patients with CAPS. [source] The effects of ziprasidone on steady-state lithium levels and renal clearance of lithiumBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue S1 2000G. Apseloff Aims, To assess the potential of ziprasidone to alter the renal clearance and steady-state serum levels of lithium. Methods, Healthy subjects who had stable serum lithium levels during the first 7 days of treatment with lithium 900 mg day,,1, given as two divided daily doses, were randomized to receive concomitant treatment with either ziprasidone, 40 mg day,,1, given as two divided daily doses, on days 9,11 followed by 80 mg day,,1, given as two divided daily doses on days 12,15 (n = 12), or placebo twice daily (n = 13). Ziprasidone or placebo was administered 2 h before each dose of lithium. Results, Ziprasidone administration was associated with a 0.07 mmol l,,1 (13%) mean increase in steady-state serum lithium levels compared with a mean increase of 0.06 mmol l,,1 (10%) with placebo. Mean renal clearance of lithium decreased by 0.09 l h,,1 (5%) in the ziprasidone group and by 0.14 l h,,1 (9%) in the placebo group. None of these differences between the two groups was statistically or clinically significant. Conclusions, Ziprasidone does not alter steady-state serum lithium concentrations or renal clearance of lithium. [source] Infliximab and the risk of latent viruses reactivation in active Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 7 2007Alessandro Lavagna MD Abstract Background: Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. Methods: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein,Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). Results: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/105 Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. Conclusions: Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring. (Inflamm Bowel Dis 2007) [source] | |||||||||||||||||||||||||