Home About us Contact
|
Home About us Contact | ||
|
|
||
Prophylactic Administration (prophylactic + administration)
Selected AbstractsAdd-on Phenytoin Fails to Prevent Early Seizures after Surgery for Supratentorial Brain Tumors: A Randomized Controlled StudyEPILEPSIA, Issue 2 2002Antonio De Santis Summary: ,Purpose: To determine the potential effectiveness of phenytoin (PHT) in preventing early postoperative seizures in patients undergoing craniotomy for supratentorial brain tumors. Methods: Two hundred patients requiring elective craniotomy for supratentorial brain tumors were randomized to two groups of equal size, with a prospective, open-label, controlled design. One group received PHT (18 mg/kg as an intravenous intraoperative load, followed by additional daily doses aimed at maintaining serum PHT concentrations within the 10- to 20-æg/ml range) for 7 consecutive days. In the other group, PHT was not administered. More than 90% of patients in both groups continued to take preexisting anticonvulsant medication (AEDs) with carbamazepine or phenobarbital throughout the study. The primary efficacy end point was the number of patients remaining free from seizures during the 7-day period after the operation. Results: Of 100 patients allocated to PHT, 13 experienced seizures during the 7-day observation period, compared with 11 of 100 patients in the placebo group (p > 0.05). Most seizures occurred in the first day after surgery in both groups. There were no differences between groups in the proportion of patients experiencing more than one seizure, but there was a trend for generalized seizures to be more common in PHT-treated patients than in controls (11 vs. five patients, respectively). Status epilepticus occurred in one patient in the PHT group and in two patients in the control group. Of the 13 PHT-treated seizure patients, 11 had serum PHT concentrations within the target range, and only two had concentrations below range on the days their seizures occurred. Conclusions: PHT, given at dosages producing serum concentrations within the target range, failed to prevent early postoperative seizures in patients treated with concomitant AEDs. Prophylactic administration of PHT cannot be recommended in these patients. [source] Small molecule , -amyloid inhibitors that stabilize protofibrillar structures in vitro improve cognition and pathology in a mouse model of Alzheimer's diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2010Cheryl A. Hawkes Abstract ,-Amyloid (A,) peptides are thought to play a major role in the pathogenesis of Alzheimer's disease. Compounds that disrupt the kinetic pathways of A, aggregation may be useful in elucidating the role of oligomeric, protofibrillar and fibrillar A, in the etiology of the disease. We have previously reported that scyllo -inositol inhibits A,42 fibril formation but the mechanism(s) by which this occurs has not been investigated in detail. Using a series of scyllo -inositol derivatives in which one or two hydroxyl groups were replaced with hydrogen, chlorine or methoxy substituents, we examined the role of hydrogen bonding and hydrophobicity in the structure,function relationship of scyllo -inositol,A, binding. We report here that all scyllo -inositol derivatives demonstrated reduced effectiveness in preventing A,42 fibrillization compared with scyllo -inositol, suggesting that scyllo -inositol interacts with A,42 via key hydrogen bonds that are formed by all hydroxyl groups. Increasing the hydrophobicity of scyllo -inositol by the addition of two methoxy groups (1,4-di- O -methyl- scyllo -inositol) produced a derivative that stabilized A,42 protofibrils in vitro. Prophylactic administration of 1,4-di- O -methyl- scyllo -inositol to TgCRND8 mice attenuated spatial memory impairments and significantly decreased cerebral amyloid pathology. These results suggest that A, aggregation can be targeted at multiple points along the kinetic pathway for the improvement of Alzheimer's disease-like pathology. [source] CNTO 859, a humanized anti-tissue factor monoclonal antibody, is a potent inhibitor of breast cancer metastasis and tumor growth in xenograft modelsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Cam V. Ngo Abstract Thromboembolic complications are frequently associated with advanced cancer. Interestingly, one of the major initiators of blood coagulation, tissue factor (TF), is reported to be overexpressed in several tumor types and can be found on both tumor cells and tumor vasculature. Although the exact mechanisms have yet to be elucidated, TF expressed on tumor cells can trigger intracellular signaling events through various pathways that can lead to tumor angiogenesis, proliferation, and metastasis. There exists preclinical evidence that disruption of TF dependent signaling can effectively inhibit tumor cell migration, metastasis, and angiogenesis. Here, we report for the first time that an antibody to tissue factor can also prevent tumor growth in vivo. Prophylactic administration of CNTO 859, a humanized anti-human TF antibody, was shown to inhibit experimental lung metastasis of MDA-MB-231 human breast carcinoma cells by over 99% compared to a control antibody. Furthermore, therapeutic doses of CNTO 859 were shown to reduce tumor incidence and growth of orthotopically implanted MDA-MB-231 cells. © 2006 Wiley-Liss, Inc. [source] Randomized clinical trial to assess the efficacy of ulinastatin for postoperative pancreatitis following pancreaticoduodenectomyJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2008Kenichiro Uemura MD Abstract Background and Objectives Ulinastatin, an intrinsic trypsin inhibitor, has proved to be effective for the prevention of acute pancreatitis after endoscopic retrograde cholangiopancreatography. The aim of this study was to assess the efficacy of ulinastatin for postoperative pancreatitis following pancreaticoduodenectomy in a randomized clinical trial. Methods Patients undergoing pancreaticoduodenectomy were randomized to receive perioperative ulinastatin or placebo. Levels of serum amylase, drain amylase, and urine trypsinogen-2 were measured. Results A total of 42 patients were enrolled (20 in the ulinastatin group, 20 in the placebo group, 2 excluded). Two patients in the ulinastatin group and nine patients in the placebo group developed hyperamylasemia (P,=,0.013) No patient in the ulinastatin group and five patients in the placebo group developed pancreatitis (P,=,0.016). One patient in the ulinastatin group and two patients in the placebo group developed grade A pancreatic fistula (P,=,0.548). Serum amylase levels at 4 hr and postoperative days 1, 2, and 3, and drain amylase levels on days 2 and 3 were significantly lower in the ulinastatin group than in the placebo group. Conclusions Prophylactic administration of ulinastatin reduced the levels of serum and drain amylase and the incidence of postoperative pancreatitis following pancreaticoduodenectomy. J. Surg. Oncol. 2008;98:309,313. © 2008 Wiley-Liss, Inc. [source] Inhibition of NKG2D receptor function by antibody therapy attenuates transfer-induced colitis in SCID miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2007Stine Kjellev Dr. Abstract A role for the activating NK-receptor NKG2D has been indicated in several autoimmune diseases in humans and in animal models of type 1 diabetes and multiple sclerosis, and treatment with monoclonal antibodies to NKG2D attenuated disease severity in these models. In an adoptive transfer-induced model of colitis, we found a significantly higher frequency of CD4+NKG2D+ cells in blood, mesenteric lymph nodes, colon, and spleen from colitic mice compared to BALB/c donor-mice. We, therefore, wanted to study the effect of anti-NKG2D antibody (CX5) treatment initiated either before onset of colitis, when the colitis was mild, or when severe colitis was established. CX5 treatment decreased the detectable levels of cell-surface NKG2D and prophylactic administration of CX5 attenuated the development of colitis significantly, whereas a more moderate reduction in the severity of disease was observed after CX5 administration to mildly colitic animals. CX5 did not attenuate severe colitis. We conclude that the frequency of CD4+NKG2D+ cells increase during development of experimental colitis. NKG2D may play a role in the early stages of colitis in this model, since early administration of CX5 attenuated disease severity. [source] Prophylactic steroids for paediatric open-heart surgery: a systematic reviewINTERNATIONAL JOURNAL OF EVIDENCE BASED HEALTHCARE, Issue 4 2008Suzi Robertson-Malt BHSc PhD Background, The immune response to cardiopulmonary bypass in infants and children can lead to a series of post-operative morbidities and mortality, that is, hemodynamic instability, increased infection and tachyarrhythmias. Administration of prophylactic doses of corticosteroids is sometimes used to try and ameliorate this pro-inflammatory response. However, the clinical benefits and harms of this type of intervention in the paediatric patient remain unclear. Objectives, To systematically review the beneficial and harmful effects of the prophylactic administration of corticosteroids, compared with placebo, in paediatric open-heart surgery. Search strategy, The trials registry of the Cochrane Heart Group, the Cochrane Central Register of Controlled Trials in The Cochrane Library (Issue 4, 2006), MEDLINE (1966 to January 2007), EMBASE (1980 to January 2007) were searched. An additional hand-search of the EMRO database for Arabic literature was performed. Grey literature was searched, and experts in the field were contacted for any unpublished material. No language restrictions were applied. Selection criteria, All randomised and quasi-randomised controlled trials of open-heart surgery in the paediatric population that received corticosteroids pre-, peri- or post-operatively, with reported clinical outcomes in terms of morbidity and mortality. Data collection and analysis, Eligible studies were abstracted and evaluated by two independent reviewers. All meta-analyses were completed using RevMan4.2.8. Weighted mean difference (WMD) was the primary summary statistic with data pooled using a random-effects model. Main results, All cause mortality could not be assessed as the data reports were incomplete. There was weak evidence in favour of prophylactic corticosteroid administration for reducing intensive care unit stay, peak core temperature and duration of ventilation (WMD (95% confidence intervals) ,0.50 h (,1.41 to 0.41); ,0.20°C (,1.16 to 0.77) and ,0.63 h (,4.02 to 2.75) respectively). [source] Exclusive use of acid citrate dextrose for anticoagulation during extracorporeal photopheresis in patients with contraindications to heparin: An effective protocol,JOURNAL OF CLINICAL APHERESIS, Issue 2 2008Elena Nedelcu Abstract Extracorporeal photopheresis (ECP) routinely uses heparin for anticoagulation. For patients with contraindications to heparin, alternative anticoagulation using acid citrate dextrose (ACD-A) has been reported to be safe and effective. However, detailed ECP protocols that exclusively use ACD-A anticoagulation and minimize citrate toxicity have not yet been published. We report a protocol that completely replaces heparin with ACD-A for ECP, which was developed at the University of California, Los Angeles (UCLA), and our experience since its implementation. ECP was performed with the UVAR XTS photopheresis system using ACD-A and control of the rate of citrate infusion. Calcium gluconate solution was administered prophylactically and as needed for symptoms of citrate toxicity. The medical records of patients who underwent ECP using the ACD-A protocol between January 2003 and July 2006 were reviewed. The incidence and severity of citrate toxicity and the technical data for all procedures were analyzed. During this period, 94 ECP procedures were performed with ACD-A anticoagulation on five patients. All patients tolerated the procedures well without significant complications. Only minimal symptoms of citrate toxicity (grade 1) were observed in 24.5% of all procedures; symptoms resolved promptly following administration of additional calcium gluconate. In conclusion, an effective protocol for ECP using ACD-A anticoagulation exclusively in patients with contraindications to heparin employs continuous monitoring of flow rates and prophylactic administration of calcium gluconate to minimize citrate toxicity. J. Clin. Apheresis, 2008. Published 2008 Wiley-Liss, Inc. [source] A survey of entodiniomorphid ciliates in chimpanzees and bonobosAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2010ina Pomajbíková Abstract Intestinal entodiniomorphid ciliates are commonly diagnosed in the feces of wild apes of the genera Pan and Gorilla. Although some authors previously considered entodiniomorphid ciliates as possible pathogens, a symbiotic function within the intestinal ecosystem and their participation in fiber fermentation has been proposed. Previous studies have suggested that these ciliates gradually disappear under captive conditions. We studied entodiniomorphid ciliates in 23 captive groups of chimpanzees, three groups of captive bonobos and six populations of wild chimpanzees. Fecal samples were examined using Sheather's flotation and Merthiolate-Iodine-Formaldehyde Concentration (MIFC) methods. We quantified the number of ciliates per gram of feces. The MIFC method was more sensitive for ciliate detection than the flotation method. Ciliates of genus Troglodytella were detected in 13 groups of captive chimpanzees, two groups of bonobos and in all wild chimpanzee populations studied. The absence of entodiniomorphids in some captive groups might be because of the extensive administration of chemotherapeutics in the past or a side-effect of the causative or prophylactic administration of antiparasitic or antibiotic drugs. The infection intensities of ciliates in captive chimpanzees were higher than in wild ones. We suppose that the over-supply of starch, typical in captive primate diets, might induce an increase in the number of ciliates. In vitro studies on metabolism and biochemical activities of entodiniomorphids are needed to clarify their role in ape digestion. Am J Phys Anthropol 2010. © 2009 Wiley-Liss, Inc. [source] Pharmacokinetics and tissue distribution of intravenous pefloxacin for antibiotic prophylaxis in biliary surgeryBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2002A.R. Gascón Abstract The plasma levels and tissue penetration of pefloxacin were studied after prophylactic administration to patients undergoing elective biliary surgery. Pefloxacin was administered as a single dose of 800 mg given intravenously as an infusion 1 h before surgery. Over a period of two years, cultures of bile and stone were performed after cholecystectomy in order to find the main pathogens present in the geographical area of the hospital of Txagorritxu (Vitoria, Spain), as well as to test the antimicrobial susceptibility of these bacteria to pefloxacin. Thirty seven per cent of the bile and stone cultures were positive, and 75 different species were isolated. E. coli was the predominant microorganism (25%). Other frequent microorganisms were E. faecium (9.3%), S. epidermidis (6.6%) and Cl. perfringens (6.6%). Most species isolated were susceptible to pefloxacin, with MIC90 values of 0.125 ,g/ml for E. coli, 0.5 ,g/ml for S. epidermidis and 1 ,g/ml for Cl. perfringens. E. faecium was resistant, with a MIC90 value of 8 ,g/ml but a MIC50 of 4 ,g/ml (intermediate). After pefloxacin infusion, adequate drug plasma levels (>MIC90) for the most frequent pathogens were found throughout the procedure. Elimination half-life was estimated as 22.03±6.91 h; the area under the concentration,time curve from zero to infinite had a value of 275.07±130.02 mg h/l and the values for volume of distribution at steady-state and plasma clearance were 96.48±28.65 L and 3.60±1.83 l/h, respectively. Bile pefloxacin concentrations generally exceeded the minimum inhibitory concentrations for most relevant pathogens. Drug levels in gallbladder and subcutaneous tissues were also above the MIC90 for extended periods. Patients were observed daily throughout their hospital stay. This included examination of the surgical wound and recording of body temperature. No cases of anaerobic infection were noted in the study patients. Other constants such as hospitalization stay and time of recuperation were normal for this type of surgery. According to these results, pefloxacin presents many features that make it suitable for use as a therapeutic prophylactic agent, such as its broad spectrum of antimicrobial activity and favorable pharmacokinetic properties. Copyright © 2002 John Wiley & Sons, Ltd. [source] Limited predictability of amikacin clearance in extreme premature neonates at birthBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2006Karel Allegaert Aim Identify and quantify factors describing variability of amikacin clearance in preterm neonates at birth. Methods Population pharmacokinetics of amikacin were estimated in a cohort of 205 extreme preterm neonates [post conception age (PCA) 27.8, SD 1.8, range 24,30 weeks; weight 1.07, SD 0.34, range 0.45,1.98 kg, postnatal age <,72 h]. Covariate analysis included weight, PCA, Apgar score, prophylactic administration of a nonsteroidal anti-inflammatory drug (NSAID) to the neonate, maternal indomethacin and betamethasone administration, and chorioamnionitis. Results A one-compartment linear disposition model with zero order input (0.3 h i.v. infusion) and first-order elimination was used. The population parameter estimate for volume of distribution (V) was 40.2 l per 70 kg. Clearance (CL) increased from 0.486 l h,1 per 70 kg at 24 weeks PCA to 0.940 l h,1 per 70 kg by 30 weeks PCA. The population parameter variability (PPV) for CL and V was 0.336 and 0.451. The use of a NSAID (either aspirin or ibuprofen) in the first day of life reduced amikacin clearance by 22%. Overall 65% of the variability of CL was predictable. Weight explained 48%, PCA 15% and NSAIDs 2%. Conclusions Size and post-conception age are the major contributors to clearance variability in extreme premature neonates (<31 weeks PCA). The large (35% of total) unexplained variability in clearance reinforces the need for target concentration intervention to reduce variability in exposure to a safe and effective range. [source] | |||||||||||||