High-dose hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) administration reduces neuronal injury and improves outcomes in experimental models of acute ischemic stroke, and has been shown to be safe in a phase 1 dose-escalation study using lovastatin at doses higher than currently approved for daily use. Statins also affect the hemostatic ...

Background This Phase I study assessed the safety and maximum tolerated dose (MTD) of the kinesin spindle protein inhibitor AZD4877 in patients with relapsed/refractory solid tumors and lymphoma. Methods In this multicenter study, a standard 3 + 3 dose-escalation design was used. AZD4877 was given as an intravenous infusion on days 1, ...

OBJECTIVE: To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). STUDY DESIGN: P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International ...

OBJECTIVES:: To compare cerebrospinal fluid (CSF) darunavir and ritonavir concentrations in patients receiving darunavir/ritonavir 800/100 mg once daily or 600/100 mg twice daily. To determine the influence of single nucleotide polymorphisms in the genes encoding for blood-brain barrier transporters (ABCB1 3435 C>T, ABCB1 1236 C>T, ABCB1 2677 G>T, SLCO1A2 38 A>G, SLCO1A2 ...

ABSTRACT:: We describe an unintentional significant overdose of darunavir in a treatment-experienced adolescent with decreased darunavir susceptibility and prior treatment failure on darunavir therapy. Minimal toxicity and improved virologic suppression observed with an overdose have prompted consideration of the continued use of a higher than recommended dose. Pharmacokinetic and pharmacodynamic ...

OBJECTIVE:Long-term efavirenz desensitization protocols have been reported; however, publication of a rapid desensitization protocol has not been noted to date. We report a case of severe hypersensitivity reaction that was successfully managed using a rapid desensitization protocol.CASE SUMMARY:In a 52-year old HIV-positive woman, antiretroviral therapy was started with lamivudine 150 ...

PURPOSE: Lersivirine is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with a unique resistance profile that exhibits potent antiretroviral activity against wild-type human immunodeficiency virus and clinically relevant NNRTI-resistant strains. Results from in vitro and in vivo investigations suggest that lersivirine is a cytochrome P450 (CYP3A4) inducer that is metabolized ...

Summary.  OBI-1 is a recombinant B-domain deleted porcine factor VIII (FVIII). FVIII treatment in those with haemophilia A may be complicated by the development of anti-FVIII antibodies (inhibitors) leading to a failure to respond to treatment with human FVIII. To compare the pharmacokinetics and safety of a single dose of ...

Vaniprevir (MK-7009) is a macrocyclic hepatitis C virus (HCV) NS3/4A protease inhibitor. The aim of the present phase 2 study was to examine virologic response rates with vaniprevir in combination with peginterferon (PEG-IFN) alfa-2a plus ribavirin. In this double-blind, placebo-controlled, dose-ranging study, treatment-naive patients with HCV genotype 1 infection (n ...

BACKGROUND:: The objective of this phase I trial was to determine dose-limiting toxicities (DLT) and the maximally tolerated dose of the radiosensitizer Nelfinavir in combination with concurrent chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC). METHODS:: Nelfinavir (dose level 1: 625 mg orally [PO] twice a day; dose level ...

To review the literature concerning the role of raltegravir in the treatment of HIV-1 in antiretroviral (ARV)-experienced and ARV-naïve patients. A PubMed search was conducted for published data through March 2012 using the search terms raltegravir, MK-0518, and integrase strand transfer inhibitor. An additional search of International Pharmaceutical Abstracts for ...

The aim of this open-label, fixed-sequence study was to investigate the potential of the botanical supplement milk thistle (silymarin) to interact with the boosted protease inhibitor combination darunavir/ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy with darunavir/ritonavir (600/100 mg twice daily) for at least 4 weeks were included. Silymarin (150 mg ...

BACKGROUND: Some difficult cases of idiopathic nephrotic syndrome (NS) have been treated with a HIV protease inhibitor provided with proteasome-inhibiting activity. The objective of this study was to limit nuclear factor κB (NF-κB) activation which is up-regulated in these patients, aiming at decreasing proteinuria and prednisone need.METHODS: Ten cases with ...

BACKGROUND: The addition of direct-acting antivirals to pegylated interferon-α plus ribavirin for the treatment of chronic HCV infection can result in an increased sustained viral response rate and may permit reduction in treatment duration. IDX320 is a potent non-covalent macrocyclic inhibitor of the HCV NS3/4A protease. METHODS: This was a ...

OBJECTIVES: The aim of the study was to evaluate fat tissue distribution in HIV-infected patients with suppressed viraemia treated with darunavir/ritonavir (darunavir/r) monotherapy versus darunavir/r triple therapy. METHODS: This study was a substudy of the randomized, multicentre, open-label MONOI-ANRS 136 trial. Body fat distribution and metabolic parameters were measured at ...

Background and Objective: Tenofovir dipivoxil fumarate (9-[(R)-2-[[bis (pivaloyloxymethoxy) phosphinoyl] methoxy] propyl] adenine fumarate) is a novel ester prodrug of tenofovir. It has been developed as an anti-hepatitis B virus clinical candidate. The purpose of this study was to determine the pharmacokinetic parameters of tenofovir dipivoxil fumarate (test) and the commercially ...

ABSTRACT: BACKGROUND: As stavudine remains an important and widely prescribed drug in resource-limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question. METHODS: We analyzed prospectively collected data from the ...

Eltrombopag is an orally bioavailable thrombopoietin receptor agonist approved for the treatment of chronic idiopathic thrombocytopenic purpura. It is being developed for other medical disorders associated with thrombocytopenia. Patients with human immunodeficiency virus (HIV) may suffer from thrombocytopenia as a result of their HIV disease or co-infection with HCV. HIV ...

PURPOSE: Decitabine is a nucleoside analog used in the treatment for myelodysplastic syndrome. The compound requires intracellular conversion to its triphosphate to become active. Decitabine triphosphate has, however, never been quantified in peripheral blood mononuclear cells (PBMCs) from patients. METHOD: This article describes a method for the quantitative determination of ...

In a retrospective database study at two HIV treatment centres, medical records were accessed to evaluate long-term efficacy and safety parameters in all HIV-infected adults who had achieved HIV-1 RNA <50 copies/mL following the initiation of fosamprenavir (FPV)/ritonavir (RTV) 1400 mg/100 mg once-daily (QD)-containing regimens between January 2004 and January ...

BMS-663749, a phosphonooxymethyl prodrug 4 of the HIV-1 attachment inhibitor 2-(4-benzoyl-1-piperazinyl)-1-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoethanone (BMS-488043) (2) was prepared and profiled in a variety of preclinical in vitro and in vivo models designed to assess its ability to deliver parent drug following oral administration. The data showed that prodrug 4 had excellent potential to ...

Introduction: GSK2248761 is a novel, once-daily (QD), next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains. Two phase I/IIa, double-blind, randomized, placebo-controlled studies investigated the antiviral activity, safety, and pharmacokinetics (PK) of several doses of GSK2248761 monotherapy in treatment-naive, HIV-infected subjects.Methods: In the initial study, 10 subjects (8 ...

Marijuana dependence is a substantial public health problem, with existing treatments showing limited efficacy. In laboratory and clinical studies, the cannabinoid receptor 1 agonist oral Δ9tetrahydrocannabinol (THC; dronabinol) has been shown to decrease marijuana withdrawal but not relapse. Dronabinol has poor bioavailability, potentially contributing to its failure to decrease relapse. ...

Pre-clinical studies suggest that the neurokinin-1 (NK(1) ) receptor may modulate the response to opioids, with NK(1) inactivation leading to decreased opioid reinforcement, tolerance and withdrawal. Aprepitant is a selective NK(1) antagonist currently marketed for clinical use as an anti-emetic. This 6-week in-patient study used a randomized, double-blind, double-dummy, within-subject, ...

PURPOSE: We measured organ specific radiation dose rates and determined effective dose rates during simulated ureteroscopy using a validated model. To calculate the effective dose, patients were exposed to ureteroscopic management of stones at our institution. MATERIALS AND METHODS: A validated anthropomorphic male phantom was placed on a fluoroscopy table ...

Objective  To evaluate the effects of a constant rate infusion (CRI) of lidocaine alone or in combination with ketamine on the minimum infusion rate (MIR) of propofol in dogs and to compare the hemodynamic effects produced by propofol, propofol-lidocaine or propofol-lidocaine-ketamine anesthesia. Study design  Prospective, randomized cross-over experimental design. Animals  ...

PURPOSE: Carmustine is a nitrosurea alkylating agent predominantly used at Peter MacCallum Cancer Centre as part of the autologous stem cell transplant induction regimens Stanford BCNU and BEAM. Acute infusion reactions were anecdotally reported to be higher than the reported rates of 10%, and it was suggested that the rate ...

BACKGROUND: Tigecycline, a broad-spectrum antibiotic used for treating serious bacterial infections in adults, may be suitable for pediatric use once an appropriate dosage is determined. OBJECTIVE: The aim of this study was to assess the pharmacokinetic (PK) properties, safety profile, and descriptive efficacy of tigecycline. METHODS: In this Phase II, ...

We investigated daily needle applicator displacement during multifractionated high-dose-rate interstitial brachytherapy (HDR-ISBT) for postoperative recurrent uterine cancer. Eight patients with postoperative recurrent uterine cancer received HDR-ISBT with or without external beam radiotherapy using our unique ambulatory technique. To analyze displacement, we obtained daily computed tomography (CT) images for 122 flexible ...

The relationship between the reported ambient dose equivalent (H*(10)) and the individual dose rate recorded by medical staff in Fukushima City after the accident at the Fukushima Daiichi nuclear power plant was evaluated, following a 9.0-magnitude earthquake that struck the east coast of Japan. Personal dose equivalent (H(p)(10)) ranged from ...

A high-dose-rate (HDR) 192-Ir brachytherapy using a customized intraoral mold is effective for superficial oral cavity cancer, and the surrounding normal tissue is kept away from the radioactive source with gauze pads and/or mouth piece for reducing the dose on the normal tissues. In the Tokushima university hospital, the mold ...

In this study, we evaluated the impact of 2 common β1-adrenergic receptor (β1-AR) polymorphisms (G389R and S49G) in response to ventricular rate control therapy in patients with atrial fibrillation (AF). Randomized studies have shown that ventricular rate control is an acceptable treatment strategy in patients with AF. However, identification of ...

Objective  To determine constant rate infusion (CRI) protocols for romifidine (R) and romifidine combined with butorphanol (RB) resulting in constant sedation and romifidine plasma concentrations. Study design  Blinded randomized crossover study. Animals  Ten adult research horses. Methods  Part I: After determining normal height of head above ground (HHAG = 100%), loading doses ...

1,4-Dioxane is one of the by-products from the polyester manufacturing process, which has been carelessly discharged into water bodies and is a weak human carcinogen. In this study, a laboratory-scale, up-flow biological aerated filter (UBAF), packed with tire chips, was investigated for the treatment of 1,4-dioxane. The UBAF was fed ...

Purpose: To experimentally investigate the effects of variations in respiratory motion during breath-holding (BH) at end-exhalation (EE) on intensity-modulated radiotherapy (BH-IMRT) dose distribution using a motor-driven base, films, and an ionization chamber.Methods: Measurements were performed on a linear accelerator, which has a 120-leaf independently moving multileaf collimator with 5-mm leaf ...

Delivery quality assurance (DQA) of tomotherapy plans is routinely performed with silver halide film which has a limited range due to the effects of saturation. DQA plans with dose values exceeding this limit require the dose of the entire plan to be scaled downward if film is used, to evaluate ...

Heterogeneities existing in the patient during treatment are neglected, as the treated subject is considered homogeneous in most of the commercially-available treatment planning systems (TPSs) used for high dose rate (HDR) brachytherapy. The choice of a suitable dosimeter for experimental dosimetry near the HDR source is crucial, mainly due to ...

The skyshine radiation phenomenon consists of the scattering of primary photon beams in the atmosphere above the roof of a medical linear accelerator facility, generating an additional dose at ground level in the vicinity of the treatment room. Thus, with respect to radioprotection, this situation plays an important role when ...

ABSTRACT The Rikers Island Key Extended Entry Program (KEEP) has offered methadone treatment for opioid dependent inmates incarcerated in New York City's jails since 1986. In response to a trend toward low-dose methadone maintenance prescribing, a quality improvement (QI) protocol trained KEEP counselors, physicians, and pharmacists in the evidence base ...

Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuroprotective potential following middle cerebral artery occlusion (MCAO) in rats. ...

The optimal injection dose for imaging of the pelvic region in 3D FDG PET tests was investigated based on the noise-equivalent count (NEC) rate with use of an anthropomorphic pelvis phantom. Count rates obtained from an anthropomorphic pelvis phantom were compared with those of pelvic images of 60 patients. The ...

The aim of this study was to design a cylindrical stepwedge phantom and an appropriate treatment procedure, based on which parameters of tomotherapy machine and generated beam of radiation will be defined. The accuracy of parameter determination, which can be defined with the aid of the measurement system, was also ...

A new class of amidine-oxime reactivators of organophosphate (OP)-inhibited cholinesterases (ChE) was synthesized and tested in vitro and in vivo. Compared with 2-PAM, the most promising cyclic amidine-oxime (i.e., 12e) showed comparable or greater reactivation of OP-inactivated AChE and OP-inactivated BChE. To the best of our knowledge, this is the ...

A novel long-lasting insecticide-treated net (LLIN) has been designed by embedding the pyrethroids deltamethrin, cyfluthrin, permethrin, or etofenprox, onto the fibres of bed net cotton fabric by transferring a new polymer-coating technique from clothing to netting material. EN ISO 6330, the more stringent European Norm for domestic washing and drying ...

Fidaxomicin is a first-in-class macrocyclic antibacterial that primarily demonstrates activity against species of clostridia, predominantly Clostridium difficile, while having limited or no activity against normal faecal microflora. Fidaxomicin is minimally absorbed following oral administration and is excreted almost solely in the faeces. Fidaxomicin displayed a high level of antibacterial activity ...

PURPOSE: Patients undergoing extensive cervical spine surgery (ECSS) occasionally require emergency reintubation due to postoperative airway complications. To avoid it, an endotracheal tube is retained in patients maintained under sedation overnight. This study was conducted to determine whether dexmedetomidine would be superior in sedative effects to propofol for postoperative sedation ...

In situ gamma spectrometric measurements have been performed to characterise the natural radiation that emitted from the stream sediment feldspars in Wadi El Missikat and Wadi Homret El Gergab, Eastern Desert, Egypt. The measurements of potassium (K, %), equivalent uranium (eU, ppm) and equivalent thorium (eTh, ppm) were converted into ...

Aims: The aim of this experiment was to determine the influence of acute bupropion pretreatment on subject-rated effects and choice of intranasal cocaine versus money. Design: A randomized, within-subject, placebo-controlled, double-blind experiment. Setting: An outpatient research unit. Participants: Eight cocaine-using adults. Measurements: Subjects completed 9 experimental sessions in which they ...

The present work deals with the prevalent radiological scenario around uranium-mining sites in the Singhbhum East district of Jharkhand state, India. The concentration of naturally occurring radioactive materials (NORMs) was estimated from 27 soil samples collected around three regions in the study area, namely Bagjata, Turamdih and Jaduguda. The mean ...

Background:  Gamma-hydroxybutyrate (GHB) may be an interesting hypnotic agent in burn patients because of its good respiratory or hemodynamic tolerance. However, its clinical and electroencephalographic (EEG) sedative effects are not yet described in children. The aim of this prospective and randomized study was to assess clinical and EEG effects of ...