To determine the recommended doses of lapatinib (LPT) combined with vinorelbine (VNR) in women with human epidermal growth factor receptor 2-overexpressing advanced breast cancer pretreated with trastuzumab. In this phase I study, women were treated with oral daily LPT and i.v. VNR infused on days 1 and 8 every 3 ...

For cardiac transplant (CTx) recipients, the recommended everolimus (EVL) dose is 0.75 mg bid or 1.5 mg bid and the target trough blood level is 3-8 μg/L. We studied a cohort of 56 CTx patients with chronic kidney disease receiving 0.75 mg bid EVL to maintain blood levels of 5-8 ug/L (designated RD group) ...

PURPOSE: To characterize exposure-response relationships of AMG 386 in a phase 2 study in advanced ovarian cancer for the facilitation of dose selection in future studies. METHODS: A population pharmacokinetic model of AMG 386 (N = 141) was developed and applied in an exposure-response analysis using data from patients (N = 160) with recurrent ...

PURPOSEOlaparib (AZD2281), an orally active poly (ADP-ribose) polymerase inhibitor that induces synthetic lethality in BRCA1- or BRCA2-deficient cells, has shown promising clinical efficacy in nonrandomized phase II trials in patients with ovarian cancer with BRCA1 or BRCA2 deficiency. We assessed the comparative efficacy and safety of olaparib and pegylated liposomal ...

PURPOSE: To analyze tangential wedged beam and field-in-field (FIF) technique doses using dose-volume histograms and conformality indices for target volume and healthy tissues within the irradiated volume. MATERIALS AND METHODS: Thirty patients treated with breast-conserving surgery and postoperative whole breast radiotherapy were enrolled. Three plans were generated: a standard tangential ...

To explore the impact of dose intensity (DI) in the adjuvant setting of breast cancer, a randomized phase III trial was conducted comparing postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide, methotrexate and fluorouracil (CMF)in high-risk breast cancer patients. From Oct 2000 to June 2005, 1,121 node-positive patients were ...

Objective-To determine the anesthetic-sparing effect of maropitant, a neurokinin 1 receptor antagonist, during noxious visceral stimulation of the ovary and ovarian ligament in dogs. Animals-Eight 1-year-old female dogs. Procedures-Dogs were anesthetized with sevoflurane. Following instrumentation and stabilization, the right ovary and ovarian ligament were accessed by use of laparoscopy. The ...

Aim This study was a retrospective analysis of our experience with severe cross-hypersensitivity reactions (HSR) to the taxanes paclitaxel (P) and docetaxel (D) in patients with breast cancer. Patients and methods We evaluated patients with breast cancer treated with P or D who experienced severe HSR to one of the ...

The objective of the study was to evaluate the safety, pharmacokinetics, and antitumor activity of ispinesib, a kinesin spindle protein inhibitor. Patients with locally advanced or metastatic breast cancer who had received only prior neoadjuvant or adjuvant chemotherapy were treated with escalating doses of ispinesib administered as a 1-h infusion ...

The objectives were: (i) improve understanding of the ovarian responses of Bos indicus heifers treated with different ovulation synchronisation protocols, (ii) compare ovarian responses of B. indicus heifers treated with intravaginal progesterone releasing device (IPRD)+oestradiol benzoate (ODB) versus a conventional prostaglandin F(2α) (PGF(2α)) protocol and (iii) investigate whether reducing the ...

BACKGROUND: The objective of this study was to evaluate 3 different doses of (7α)-21-(4-[(diethylamino)methyl]-2 methoxyphenoxy)-7 methyl-19 norpregna-1,3,5(10)-trien-3-ol 2-hydroxy-1,2,3-propanetricarboxylate (TAS-108) in patients with recurrent, hormone-responsive breast cancer. METHODS: In this randomized, double-blind, multicenter study, TAS-108 was administered daily at a dose of 40 mg, 80 mg, or 120 mg to postmenopausal ...

Purpose: Cone beam computed tomography (CBCT) is fast becoming standard on modern linear accelerators. CBCT increases the dose to regions within and outside the treatment field, potentially increasing secondary cancer induction and toxicity. This study quantified megavoltage (MV) CBCT skin dose and compared it to skin dose delivered during standard ...

Fulvestrant is a form of endocrine therapy used in the treatment of postmenopausal breast cancer. It has a unique mechanism of action in that it causes the degradation of estrogen receptor and therefore has been labeled a selective estrogen receptor downregulator. Unlike the selective estrogen receptor modulator tamoxifen, it has ...

BACKGROUND: Biologically targeted therapies have been postulated as a viable strategy to improve outcomes for women with ovarian cancer. We assessed the safety, tolerance, pharmacokinetics, relevant circulating and image-derived biomarkers, and clinical activity of combination aflibercept and docetaxel in this population. METHODS: For the phase 1 (pharmacokinetic) study, eligible patients ...

OBJECTIVES: The objective of this study was to compare the efficacy of letrozole versus clomiphene citrate as an ovulation induction drug in polycystic ovarian syndrome (PCOS) patients of Indian origin. METHOD: One hundred and forty seven infertile PCOS patients were randomly given letrozole (2.5 mg) (n = 69) or clomiphene (100 mg) (n = 78) from ...

Several case reports have indicated that a small subgroup of patients may develop ovarian hyperstimulation following the administration of gonadotropin-releasing hormone agonists (GnRHa) without gonadotropins. However, since only few such cases have been published, it is unclear what course to follow in subsequent cycles after ovarian hyperstimulation in the first ...

To measure the dose distribution, related to the treatment planning calculations, in the contralateral mammary gland of breast cancer patients treated with accelerated hypofractionated 3-dimensional conformal radiotherapy. Thirty-four prospectively selected female patients with right breast cancer (pN0, negative surgical margins) were treated with breast-conserving surgery. A total dose of 42.5 ...

To determine whether capecitabine schedule adaptation improves the tolerability of capecitabine-paclitaxel combination therapy for metastatic breast cancer (MBC), patients with anthracycline-pretreated HER2-negative MBC were randomized to either arm A (21-day cycles: capecitabine 1,000 mg/m(2) twice daily, days 1-14; paclitaxel 60 mg/m(2), days 1, 8, and 15) or arm B (28-day cycles: capecitabine ...

Objective: Recent publications have shown the use of a generic conversion factor for CT coronary angiography (CTCA) in the range 0.014-0.019 mSv/(mGy × cm) returns a significant underestimate of effective dose. The aim of this manuscript is to communicate new dosimetry methods to calculate weighted CT dose index, effective dose, entrance ...

ABSTRACT: BACKGROUND: A new algorithm for photon dose calculation, Acuros XB, has been recently introduced in the Eclipse, Varian treatment planning system, allowing, similarly to the classic Monte Carlo methods, for accurate modelling of dose deposition in media. Aim of the present study was the assessment of its behaviour in ...

Capecitabine monotherapy is considered standard treatment in anthracycline- and taxane-pretreated metastatic breast cancer and has proven efficacy in this setting. Randomized studies and retrospective analyses have shown that, in patients who received capecitabine monotherapy, or in combination with docetaxel, dose modification of capecitabine is effective in the management of adverse ...

To investigate the use of various breast tissue segmentation models in Monte Carlo dose calculations for low-energy brachytherapy. The EGSnrc user-code BrachyDose is used to perform Monte Carlo simulations of a breast brachytherapy treatment using TheraSeed Pd-103 seeds with various breast tissue segmentation models. Models used include a phantom where ...

OBJECTIVE: The aim of this study was to select the best catumaxomab regimen for further investigation in ovarian cancer based on confirmed tumour response. METHODS: Randomised open-label phase IIa study in women with platinum-resistant or -refractory epithelial ovarian cancer. Catumaxomab (6-hour intraperitoneal infusion on days 0, 3, 7 and 10) ...

: Autologous breast reconstruction by deep inferior epigastric perforator (DIEP) flap provides higher postoperative pain at the abdominal donor site than at the thoracic one. The authors evaluated the analgesic efficacy of ultrasound-guided transverse abdominis plane block for postoperative analgesia after immediate breast reconstruction by DIEP flap. : The authors ...

OBJECTIVE:: Carboplatin is one of the most effective chemotherapeutic drugs for the treatment of ovarian cancer. It has simple pharmacokinetics and a predictable toxicity profile. The dose can be calculated effectively based on a patient's renal function as defined by the glomerular filtration rate (GFR). The measurement of the GFR ...

PURPOSE: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTD) of oral metronomic vinorelbine with capecitabine in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Escalated doses of oral metronomic vinorelbine (starting dose 30 mg) every other day continuously and capecitabine (starting dose 800 mg/m(2) bid) on days ...

Great deal of work has been devoted to determine doses from alpha particles emitted by (222)Rn and (220)Rn progeny. In contrast, contribution of beta particles to total dose has been neglected by most of the authors. The present work describes a study of the detriment of (222)Rn and (220)Rn progeny ...

Postmenopausal women with hormone receptor-positive advanced breast cancer are candidates for endocrine therapy. As the disease will eventually progress in most patients, it is important to investigate agents with novel modes of action to reduce the likelihood of treatment cross-resistance. Fulvestrant is an estrogen receptor antagonist with no known agonist ...

Corifollitropin alfa is a new recombinant gonadotrophin with a different pharmacokinetic profile but similar pharmacodynamic properties to conventional recombinant FSH. A single dose of corifollitropin alfa sustains multiple follicular development during the first 7days of ovarian stimulation. This review is based on results of phase II and III trials testing ...

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel formulation of paclitaxel that does not require solvents such as polyoxyethylated castor oil and ethanol. Use of these solvents has been associated with toxic response, including hypersensitivity reactions and prolonged sensory neuropathy, as well as a negative impact in relation to the therapeutic ...

Paclitaxel is a diterpenoid isolated from Taxus brevifolia. It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor(®) EL (BASF, Ludwigshafen, Germany), which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was ...

ABSTRACT: The aim of the present study was to explore the biodistribution, normal tissue toxicity, and therapeutic efficacy of the internalizing low-dose rate alpha-particle-emitting radioimmunoconjugate 227Th-trastuzumab in mice with HER2-expressing breast cancer xenografts. Biodistribution of 227Th-trastuzumab and 227Th-rituximab in nude mice bearing SKBR-3 xenografts were determined at different time points ...

Cisplatin is a potent anticancer drug, but its clinical application has been limited due to its undesirable physicochemical characteristics and severe side effects. Better drug formulations for cisplatin are highly desired. Herein, we have developed a nanoparticle formulation for cisplatin with high encapsulation efficiency and reduced toxicity by using cisplatin-crosslinked ...

We planned this study in order to investigate the effects of theophylline on cardiovascular parameters in an anaesthetized rat model of amitriptyline toxicity. In the preliminary study, we tested theophylline as 1 mg/kg of bolus, followed by a 0.5-mg/kg infusion. Toxicity was induced by the infusion of 0.94 mg/kg/min of amitriptyline up ...

Extrapyramidal syndromes (EPS) impose a heavy burden on patients receiving antipsychotic therapy. Anticholinergics are the drugs of choice for preventing EPS, but they also produce many adverse reactions. Using the EPS model of haloperidol-induced catalepsy we evaluated the potential therapeutic value of a mixture of low doses of the non-selective ...

To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low-dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 +/- 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, ...

Xanthines such as theophylline have been used in the treatment of lung diseases since the early 1900's, but have a major drawback of a very narrow therapeutic window and many drug/drug interactions. With the increasing availability of other classes of drugs, this has limited the use of xanthines. Doxofylline is ...

BACKGROUND: Inhaled corticosteroids (ICS) have proved disappointing at reducing airway inflammation in COPD. However, previous studies indicate that low doses of theophylline enhance the activity of a key corticosteroid-associated corepressor protein, histone deacetylase (HDAC)2, which is reduced in COPD. This may account, at least in part, for the relative corticosteroid ...

In the present study, the antiasthmatic (bronchodilatory) effect of the boiled extract of Nigella sativa in the airways of asthmatic patients was examined. The bronchodilatory effects of 50 and 100 mg/kg of boiled extract in comparison with 6 mg/kg theophylline were studied on 15 asthmatic patients. Pulmonary function tests (PFTs) ...

Theophylline can induce life-threatening seizures in humans, especially in infants, but the mechanism of induction remains unknown. We investigated the effects of orally administered theophylline on mouse electroencephalograms (EEGs). ddY mice, which are generally completely free of seizures, were used for the experiments. While EEGs, used as controls, showed no ...

Although there are many new specific phosphodiesterase inhibitors with anti-inflammatory activity, none have yet reached the market because of their low therapeutic efficacy. Our study was aimed to evaluate the anti-inflammatory and anti-arthritic effect of an established phosphodiesterase inhibitor, theophylline, and to investigate the effect of the nitric oxide (NO) ...

BACKGROUND: Theophylline has been widely used to treat asthma, but recent studies have revealed that the possible risks for seizure may result in the revision of the therapeutic guidelines. METHODS: An 8-month-old boy who had been treated with oral sustained-release theophylline and additional aminophylline suppository was hospitalized. A combination of ...

An 89-year-old man with a history of hypertension, chronic obstructive pulmonary disease, personality disorder and previous attempts of self-poisoning attempted suicide by swallowing two mouthfuls of tablets (methyldopa 250 mg, theophylline SR 200 mg, indapamide 2.5 mg and paracetamol 500 mg). He had prolonged, severe hypotension, necessitating the use of ...

BACKGROUND: The use of N-acetylcysteine or theophylline in specific subgroups of patients has been suggested to reduce the incidence of contrast-induced nephropathy (CIN) in patients undergoing angiographic procedures. Our purpose was to compare the use of N-acetylcysteine versus N-acetylcysteine + theophylline for the prevention of CIN. MATERIALS AND METHODS: We ...

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response mainly to cigarette smoke that flares up during exacerbations of the disease (ECOPD). Reduced activity of histone deacetylases (HDAC) contributes to enhanced inflammation in stable COPD. It was hypothesised that HDAC activity is further reduced during ECOPD ...

OBJECTIVE: To determine results of ultrasound-guided cystocentesis and percutaneous infusion of Walpole's solution for treatment of male goats with urolithiasis. DESIGN: Retrospective case series. ANIMALS: 25 male goats with urolithiasis treated with Walpole's solution. PROCEDURES: Information obtained from the medical records included signalment, degree of urethral obstruction (partial vs complete), ...

BACKGROUND: The threonine requirement of human neonates who receive parenteral nutrition (PN) has not been determined experimentally. OBJECTIVE: The objective was to determine the parenteral threonine requirement for human neonates by using the minimally invasive indicator amino acid oxidation technique with L-[1-(13)C]phenylalanine as the indicator amino acid. DESIGN: Nine postsurgical ...

OBJECTIVE: The aim of this study was to describe the clinical effects of promethazine in overdose and explore the relationship between delirium and possible predictor variables. METHODS: A case series of promethazine poisonings was identified from a prospective database of poisoning admissions to a regional toxicology service. Data were extracted ...

Hypertension and dyslipidemia are independent risk factors for cardiovascular mortality and are frequently present in the same patient. Fluvastatin (FV), used to reduce cholesterol levels, and lercanidipine (LER), used to control blood pressure, are marketed as racemic mixtures. Therapeutic activities are 30-fold higher for (+)-3R, 5S-FV and 100- to 200-fold ...

BACKGROUND: Tetrahydrobiopterin (BH(4)) loading has been performed for many years in patients detected by newborn screening for hyperphenylalaninaemia (HPA) to distinguish BH(4) cofactor synthesis or recycling defects from phenylalanine hydroxylase (PAH)-deficient HPA. Previous studies have shown that the pharmacokinetics of BH(4) shows high intra-individual and inter-individual variability. METHODS: Seventeen adult ...