Current Issue : April - June Volume : 2013 Issue Number : 2 Articles : 6 Articles
Background: The addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first\r\nline treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and\r\nactivity of a lower dose of bevacizumab in pretreated advanced stage EOC.\r\nMethods: We treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior\r\ncytotoxic regimens, with bevacizumab 5ââ?¬â??7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral\r\ncyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor\r\nresponse was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT.\r\nResults: The median number of bevacizumab cycles was 21 (range 3ââ?¬â??59). The median baseline CA125 was 272 U/\r\nml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial\r\nresponse (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 ââ?¬â?? 95.8) according\r\nto Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall\r\nmetabolic response rate of 67% (95%CI, 42.8 ââ?¬â?? 90.6) according to PET Response Criteria in Solid Tumors (PERCIST).\r\nMedian progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3\r\nadverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment\r\nwas delayed in five patients for nasal bleeding or uncontrolled hypertension.\r\nConclusions: Low-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated\r\npopulation of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC....
Background: Shivering and fever are common side effects of misoprostol. An unexpectedly high rate of fever\r\nabove 40�°C was documented among Ecuadorian women given treatment with 800mcg of sublingual misoprostol\r\nto manage postpartum hemorrhage (PPH) (36%). Much lower rates have been reported elsewhere (0-9%).\r\nMethods: From February to July 2010, an open-label pilot study was conducted in Quito, Ecuador to determine\r\nwhether a lower dose--600mcg sublingual misoprostol--would result in a lower incidence of high fever (=40�°C).\r\nRates of shivering and fever with 600mcg sublingual regimen were compared to previously documented rates in\r\nEcuador following PPH treatment with 800mcg sublingual misoprostol.\r\nResults: The 600mcg dose resulted in a 55% lower rate of high fever compared with the 800mcg regimen (8/50;\r\n16% vs. 58/163; 36%; relative risk 0.45 95% CI 0.23-0.88). Only one woman had severe shivering following the\r\n600mcg dose compared with 19 women in the 800mcg cohort (2% vs. 12%; relative risk 0.17 (0.02-1.25)). No cases\r\nof delirium/altered sensorium were reported with the 600mcg dose and womenâ��s assessment of severity/tolerability\r\nof shivering and fever was better with the lower dose.\r\nConclusions: 600mcg sublingual misoprostol was found to decrease the occurrence of high fever among\r\nEcuadorian women when given to treat PPH. This study however was not powered to examine the efficacy of this\r\ntreatment regimen and cannot be recommended at this time. Future research is needed to confirm whether other\r\npopulations, outside of Quito, Ecuador, experience unusually high rates of elevated body temperature following\r\nsublingual administration of misoprostol for treatment of PPH. If indeed similar trends are found elsewhere, larger\r\ntrials to confirm the efficacy of lower dosages may be justified....
Introduction: Stimulant medication improves hyperactivity, inattention, and impulsivity in both pediatric and adult\r\npopulations with Attention Deficit Hyperactivity Disorder (ADHD). However, data regarding the optimal dosage in\r\nadults is still limited.\r\nCase presentation: We report the case of a 38-year-old Caucasian patient who was diagnosed with Attention\r\nDeficit Hyperactivity Disorder when he was nine years old. He then received up to 10 mg methylphenidate\r\n(RitalinW) and 20 mg sustained-release methylphenidate (Ritalin SRW) daily. When he was 13, his medication was\r\nchanged to desipramine (NorpraminW), and both RitalinW and Ritalin SRW were discontinued; and at age 18, when\r\nhe developed obsessive-compulsive symptoms, his medication was changed to clomipramine (AnafranilW) 75 mg\r\ndaily. Still suffering from inattention and hyperactivity, the patient began college when he was 19, but did not\r\nreceive stimulant medication until three years later, when RitalinW 60 mg daily was re-established. During the 14\r\nmonths that followed, he began to use RitalinW excessively, both orally and rectally, in dosages from 4800-6000 mg\r\ndaily. Four years ago, he was referred to our outpatient service, where his Attention Deficit Hyperactivity Disorder\r\nwas re-evaluated. At that point, the patientââ?¬â?¢s daily RitalinW dosage was reduced to 200 mg daily orally, but he still\r\nexperienced pronounced symptoms of, Attention Deficit Hyperactivity Disorder so this dosage was raised again.\r\nThe patientââ?¬â?¢s plasma levels consistently remained between 60ââ?¬â??187 nmol/lââ?¬â?within the recommended rangeââ?¬â?and\r\nsigns of his obsessive-compulsive symptoms diminished with fluoxetine 40 mg daily. Finally, on a dosage of 378\r\nmg extended-release methylphenidate (ConcertaW), his symptoms of Attention Deficit Hyperactivity Disorder have\r\nimproved dramatically and no further use of methylphenidate has been recorded during the 24 months preceding\r\nthis report.\r\nConclusions: Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) in this adult patient, who also\r\nmanifested a co-occurring obsessive compulsive disorder, dramatically improved only after application of a\r\nhigher-than-normal dose of methylphenidate. We therefore suggest that clinicians consider these findings in\r\nrelation to their adherence to current therapeutic guidelines....
Background: To determine the efficacy of high-dose antioxidants in the acute stage of central serous\r\nchorioretinopathy (CSC).\r\nMethods: This was a randomized placebo-controlled study. The patients with acute CSC (onset within 6 weeks)\r\nwere randomized to receive either high-dose antioxidant tablets (study group A) or placebo tablets (control group\r\nB) for 3 months or until the complete resolution of subretinal fluid. After 3 months, additional treatment with laser\r\nor photodynamic therapy (PDT) was considered if any fluorescein leakage persisted. The outcomes measured were\r\nthe changes in visual acuity (VA) and central macular thickness (CMT), the number of patients with subretinal fluid\r\nat each follow-up time, the number of patients with fluorescein leakage at the end of the 3rd month and patients\r\nwho received additional treatments.\r\nResults: Fifty-one of 58 patients (88%) completed the follow-up criteria. The baseline demographic data were\r\ncomparable in both groups. At the end of the 3rd month, the VA and CMT showed no statistical difference\r\nbetween the groups but the patients in group A has less fluorescein leakage and additional treatments than in\r\ngroup B (p = 0.027 and 0.03).\r\nConclusion: The high-dose antioxidants for acute CSC did not show any benefits in VA and CMT. However, the\r\ndrugs might decrease the chance for fluorescein leakage and additional treatments at the end of the 3rd month....
Backgrounds: Magnesium has been known for its antioxidative and antiinflammatory properties in many studies.\r\nIn this study two dosing regimens of magnesium were compared with a placebo control group in order to\r\ninvestigate safety and efficacy of high doses of intravenous magnesium sulfate infusion on critically ill trauma\r\npatients. Inflammatory and oxidative factors were measured in this trial.\r\nMethods: 45 trauma patients with systemic inflammatory response syndromes (SIRS) were randomly assigned into\r\n2 treatment and one placebo groups. The high dose group received 15 g MgSO4, low dose group received 7.5 g\r\nof MgSO4 over 4 hour infusion, and placebo group received saline alone. The initial and post magnesium sulfate\r\ninjections levels of tumor necrosis factor alpha (TNF-a), total antioxidant power and lipid peroxidation were\r\nmeasured after 6, 18 and 36 hours. The pre-infusion along with 6 and 36 hour level of microalbuminuria were\r\nalso determined.\r\nResults: Repeated measurements illustrated that there was no significant difference in TNF-a, total antioxidant\r\npower and lipid peroxidation levels among groups during the period of analysis. The microalbuminuria at 36 hour\r\npost infusion of high dose group was lower than that of control group (p = 0.024). Patient�s mortality (28 day) was\r\nsimilar among all treatment groups. Both magnesium infusion groups tolerated the drug without experiencing\r\nany complications.\r\nConclusion: No evidence for antioxidative and antiinflammatory effects of magnesium in traumatic SIRS positive\r\npatients was found. Magnesium in high doses may be recommended for traumatic patients with SIRS status to\r\nprevent microalbuminuria....
Background: The development of analgesic tolerance following chronic morphine administration can be a significant\r\nclinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that\r\ninhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated\r\nthat ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical\r\nstudies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone\r\nattenuates glial activation, which may contribute to its effects on attenuating tolerance.\r\nResults: Spinal cord sections from rats administered chronic morphine showed significantly increased immunolabelling\r\nof astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes\r\nfrom animals administered chronic morphine had significantly larger volumes compared to saline controls. Coinjection\r\nof ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from salinetreated\r\nand naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats coadministered\r\nultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial\r\nactivation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of\r\ntolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference\r\nobserved in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore,\r\nusing 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine\r\nadministration.\r\nConclusion: Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and\r\nthe inhibition of spinal gliosis by treatment with ultra-low dose naltrexone. This research provides further validation for\r\nusing ultra-low dose opioid receptor antagonists in the treatment of various pain syndromes...
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