scholarly journals Pharmacokinetics and Safety of Intravitreal Caspofungin

2014 ◽  
Vol 58 (12) ◽  
pp. 7234-7239 ◽  
Author(s):  
Ying-Cheng Shen ◽  
Chiao-Ying Liang ◽  
Chun-Yuan Wang ◽  
Keng-Hung Lin ◽  
Min-Yen Hsu ◽  
...  
Keyword(s):  
High Performance ◽  
Potential Role ◽  
Elimination Rate ◽  
Retinal Toxicity ◽  
Primary Therapy ◽  
Time Intervals ◽  
Content Type ◽  
Fungal Endophthalmitis ◽  
Time Points ◽  
The Mean

ABSTRACTCaspofungin exhibits potent antifungal activities againstCandidaandAspergillusspecies. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 μg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 μg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 μg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopica-wave andb-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.

Annual hazard rates of recurrence for breast cancer after primary therapy.

1996 ◽  
Vol 14 (10) ◽  
pp. 2738-2746 ◽  
Author(s):  
T Saphner ◽  
D C Tormey ◽  
R Gray
Keyword(s):  
Breast Cancer ◽  
Eastern Cooperative Oncology Group ◽  
Entire Group ◽  
Hazard Rates ◽  
Primary Therapy ◽  
Time Intervals ◽  
Differentiating Agents ◽  
The Mean ◽  
Lower Hazard

PURPOSE To determine if the long-term increase of recurrence for breast cancer is stable or slowly decreasing, or if it ever reaches zero; and to determine the effect of prognostic factors on the hazard of recurrence. METHODS All patients entered onto the seven completed and unblinded Eastern Cooperative Oncology Group (ECOG) coordinated studies of postoperative adjuvant therapy for breast cancer were analyzed in terms of annual hazard of recurrence of breast cancer. RESULTS For the entire group, the peak hazard of recurrence occurred in the interval of 1 to 2 years. The hazard decreased consistently in the interval of 2 to 5 years. Beyond 5 years, the hazard of recurrence decreased very, very slowly through year 12. The average hazard of recurrence between years 5 and 12 for the entire population was 4.3% per year. The pattern of a peak hazard of recurrence during the first 5 years with a slowly decreasing hazard of recurrence beyond 5 years was also observed to varying degrees in most subsets. Higher risk subsets such as patients with more than three nodes positive had a higher hazard of recurrence at all time intervals, while lower risk subsets such as patients with negative nodes had a lower hazard of recurrence in all time periods. CONCLUSION Patients 5 years postsurgery for breast cancer appear to have a very slowly decreasing hazard of recurrence. The mean hazard of recurrence between years 5 to 12 postsurgery is 4.3% per year. This group of patients may be well suited for trials evaluating cytostatic drugs or differentiating agents.

Analysis of electromagnetic torque for induction motors with a novel non-skewed rotor structure

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Amir Darjazini ◽  
Abolfazl Vahedi ◽  
Amin Nobahari ◽  
Saber Gharehseyed
Keyword(s):  
High Performance ◽  
Induction Motors ◽  
Acoustic Noise ◽  
Torque Ripple ◽  
Iron Loss ◽  
Mechanical Equipment ◽  
Electromagnetic Torque ◽  
Content Type ◽  
The Mean ◽  
Rotor Structure

Purpose Pulsating torques cause a number of problems in electrical machines, including mechanical vibrations, acoustic noise and the depreciation of mechanical equipment. In induction motors, the slot skewing method is an effective way to solve these issues; however, it has some drawbacks such as output torque drop, stray loss intensification due to inter-bar currents and iron loss increment. Besides, slot skewing may not be practical in higher-rated induction motors. In this regard, this paper introduces a modified non-skewed rotor (MNSR) structure as a possible alternative to the skewed designs. Design/methodology/approach The proposed structure includes a two-segmented rotor with an intermediate ring between the rotor parts that are mounted on the shaft with a relative shift angle. Detailed information about the idea and structure of the MNSR as well as its manufacturing aspects will be presented in the second section of the paper. First, the working principle of the proposed design is described via analytical equations to provide an insight into the concept. The shifting angle will then be calculated by analyzing the harmonic contents of the electromagnetic torque. Finally, the validity of the analytical method will be verified by developing three-dimensional finite element models. Findings It is demonstrated that by using the proposed rotor structure, the torque ripple has been reduced to a satisfactory level without significantly affecting the mean torque, unlike the skewing method. Furthermore, the new method could avoid the disadvantages of the skewing method while enhancing other motor characteristics such as iron loss. Also, the total volume of the MNSR is equal to the initial design, and the mass and material differences are also negligible. Originality/value In this paper, a MNSR is introduced as a possible alternative to the skewed patterns. The study mainly focused on electromagnetic torque profile characteristics, i.e. the mean torque enhancement and the ripple reduction. The MNSR structure can be used for general purposes and high-performance applications, especially where excellent torque characteristics are required.

scholarly journals Population Pharmacokinetics and Dosing Optimization of Imipenem in Children with Hematological Malignancies

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Lei Dong ◽  
Xiao-Ying Zhai ◽  
Yi-Lei Yang ◽  
Li Wang ◽  
Yue Zhou ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Population Pharmacokinetics ◽  
High Performance ◽  
Hematological Malignancies ◽  
Elimination Rate ◽  
Population Level ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Content Type ◽  
Dosage Regimens

ABSTRACT Imipenem is widely used for the treatment of children with serious infections. Currently, studies on the pharmacokinetics of imipenem in children with hematological malignancies are lacking. Given the significant impact of disease on pharmacokinetics and increased resistance, we aimed to conduct a population pharmacokinetic study of imipenem and optimize the dosage regimens for this vulnerable population. After children were treated with imipenem-cilastatin (IMP-CS), blood samples were collected from the children and the concentrations of imipenem were quantified using high-performance liquid chromatography with UV detection. Then, a population-level pharmacokinetic analysis was conducted using NONMEM software. Data were collected from 56 children (age range, 2.03 to 11.82 years) with hematological malignancies to conduct a population pharmacokinetic analysis. In this study, a two-compartment model that followed first-order elimination was found to be the most suitable. The parameters of current weight, age, and creatinine elimination rate were significant covariates that influenced imipenem pharmacokinetics. As a result, 41.4%, 56.1%, and 67.1% of the children reached the pharmacodynamic target (the percentage of the time during the total dosing interval that the free drug concentration remains above the MIC of 70%) against sensitive pathogens with an MIC of 0.5 mg/liter with imipenem at 15, 20, and 25 mg/kg of body weight every 6 h (q6h), respectively. However, only 11.1% of the children achieved the pharmacodynamic target against Pseudomonas aeruginosa isolates with an MIC of 2 mg/liter at a dose of 25 mg/kg q6h. The population pharmacokinetics of imipenem were assessed in children. The current dosage regimens of imipenem result in underdosing against resistant pathogens, including Pseudomonas aeruginosa and Acinetobacter baumannii. However, for sensitive pathogens, imipenem has an acceptable pharmacodynamic target rate at a dosage of 25 mg/kg q6h. (The study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT03113344.)

scholarly journals Distribution of Linezolid in Tuberculosis Lesions in Patients with Spinal Multidrug-Resistant Tuberculosis

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
Yuan Li ◽  
Weijie Dong ◽  
Tinglong Lan ◽  
Jun Fan ◽  
Shibing Qin ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Granulation Tissue ◽  
High Performance ◽  
Multidrug Resistant ◽  
Sample Collection ◽  
Tissue Samples ◽  
Content Type ◽  
Mdr Tb ◽  
The Mean ◽  
The Difference

ABSTRACT Linezolid has strong antimicrobial activity against the multidrug-resistant (MDR) strains of Mycobacterium tuberculosis. Little is known about the distribution of linezolid in tuberculosis (TB) lesions in patients with MDR-TB. The aim of this study was to evaluate the distribution of linezolid in TB lesions in patients with spinal MDR-TB. Nine patients with spinal MDR-TB were enrolled prospectively from August 2019 to February 2020. The patients received a linezolid-containing anti-TB treatment regimen and needed surgery for the removal of TB lesions. During the operation, nine blood samples, eight diseased bone tissue samples, seven pus samples, and four granulation tissue samples were collected simultaneously and 2 h after the oral administration of 600 mg of linezolid. Linezolid concentrations in plasma, diseased bone tissue, pus, and granulation tissue samples were subjected to high-performance liquid chromatography-tandem mass spectrometry. At sample collection, the mean concentrations of linezolid in plasma, diseased bone tissue, pus, and granulation tissue samples of the nine patients were 11.14 ± 5.82, 5.94 ± 4.27, 11.09 ± 4.58, and 14.08 ± 10.61 mg/liter, respectively. The mean ratios of linezolid concentration in diseased bone/plasma, pus/plasma, and granulation/plasma were 53.84%, 91.69%, and 103.57%, respectively. The mean ratios of linezolid concentration in pus/plasma and granulation/plasma were higher than those in diseased bone/plasma, and the difference was statistically significant (t = −2.810, P = 0.015; t = −4.901, P = 0.001). In conclusion, linezolid had different concentration distributions in different types of TB-infected tissues in patients with spinal MDR-TB.

Can enhanced performance management support public sector change?

2015 ◽  
Vol 28 (2) ◽  
pp. 271-289 ◽  
Author(s):  
Fiona Buick ◽  
Deborah Ann Blackman ◽  
Michael Edward O'Donnell ◽  
Janine Louise O'Flynn ◽  
Damian West
Keyword(s):  
Public Sector ◽  
Performance Management ◽  
High Performance ◽  
Potential Role ◽  
Case Study Research ◽  
Change Implementation ◽  
Management Support ◽  
Public Servants ◽  
Content Type ◽  
Performance Framework

Purpose – The purpose of this paper is to focus on the potential role that performance management could play in enabling employees’ adaptability to change and, therefore, successful change implementation. Design/methodology/approach – This research adopted a qualitative case study research design, focussed on seven case studies within the Australian Public Service (APS). This study utilized documentary analysis, semi-structured individual and group interviews. Findings – The findings of this research demonstrate that adaptability to change is integral for high performance; however, the constant change faced by many public servants is disruptive. The authors posit that applying a performance framework developed by Blackman et al. (2013a, b) to change implementation will help overcome, or at least mitigate, these issues. The authors argue that applying this framework will: enable adaptability to change; and provide an ongoing management function that enables change to occur. Research limitations/implications – This research has been limited to seven organizations within the APS, yet it does reveal interesting implications in terms of the apparent role of performance management in both developing change capacity and supporting espoused outcomes. Practical implications – This research identifies the potential role that performance management can play in supporting effective change implementation through enabling employees to cope better with the change through enabling clarity, purpose and alignment with the organizational direction. Originality/value – The originality of this paper stems from the synthesis of different strands of literature, specifically high performance, performance management and change management, and empirical research in the public sector to provide a new way of looking at performance management as a change enabler.

scholarly journals Pertussis Serodiagnosis in Belgium from 1990 to 2009

2011 ◽  
Vol 18 (4) ◽  
pp. 588-594 ◽  
Author(s):  
Muriel Vincent ◽  
Caroline Rodeghiero ◽  
Romain Eylenbosch ◽  
Yvan Mans ◽  
Jeannine Swalus-Steenhouwer ◽  
...  
Keyword(s):  
Potential Role ◽  
Whooping Cough ◽  
Age Groups ◽  
Childhood Vaccination ◽  
Clinical Samples ◽  
Content Type ◽  
The Mean ◽  
Children And Young Adolescents ◽  
Vaccination Campaigns

ABSTRACTDiagnosis of pertussis by culture and PCR is most sensitive when performed on nasopharyngeal specimens collected <2 weeks and <3 weeks, respectively, after the onset of clinical disease. Conversely, serological testing allows the diagnosis of patients (mostly adults) with less typical whooping cough symptoms, for whom clinical samples are often collected at later time points. Here, we report on a 20-year serodiagnostic survey of pertussis in Belgium from 1990 to 2009. In total, 13,163 patients were analyzed forBordetella pertussis-specific antibodies by agglutination, complement fixation, immunofluorescence, and ELISA. The number of positive pertussis cases detected by serodiagnosis ranged between 50 and 150 annually. The mean age of positive cases increased from 9.9 years in 1990 to 33.9 years in 2009. Whereas from 1990 to 2003, children and young adolescents made up the majority of cases, from 2004 onwards, cases were detected in all age groups and the distribution became bimodal, with a first peak at the age of 10 to 20 years and a second at the age of 35 to 50 years. In contrast, patients diagnosed since 2001 by PCR and/or culture were mostly children younger than 1 year of age. Despite extensive childhood vaccination campaigns, whooping cough is still present in Belgium. Our findings confirm the potential role of adults in the continued transmission of pertussis and strongly warrant booster or cocoon vaccinations in older age groups.

Placental Transfer of Vitamin K1 and Its Implications in Fetal Hemostasis

1988 ◽  
Vol 60 (01) ◽  
pp. 039-043 ◽  
Author(s):  
L Mandelbrot ◽  
M Guillaumont ◽  
M Leclercq ◽  
J J Lefrère ◽  
D Gozin ◽  
...  
Keyword(s):  
Vitamin K ◽  
High Performance ◽  
Ultrasound Guidance ◽  
Placental Transfer ◽  
Vitamin K1 ◽  
Vitamin K Deficiency ◽  
Prothrombin Activity ◽  
Oral Supplementation ◽  
K Deficiency ◽  
The Mean

SummaryVitamin K status was evaluated using coagulation studies and/ or vitamin IQ assays in a total of 53 normal fetuses and 47 neonates. Second trimester fetal blood samples were obtained for prenatal diagnosis under ultrasound guidance. Endogenous vitamin K1 concentrations (determined by high performance liquid chromatography) were substantially lower than maternal levels. The mean maternal-fetal gradient was 14-fold at mid trimester and 18-fold at birth. Despite low vitamin K levels, descarboxy prothrombin, detected by a staphylocoagulase assay, was elevated in only a single fetus and a single neonate.After maternal oral supplementation with vitamin K1, cord vitamin K1 levels were boosted 30-fold at mid trimester and 60 fold at term, demonstrating placental transfer. However, these levels were substantially lower than corresponding supplemented maternal levels. Despite elevated vitamin K1 concentrations, supplemented fetuses and neonates showed no increase in total or coagulant prothrombin activity. These results suggest that the low prothrombin levels found during intrauterine life are not due to vitamin K deficiency.

Gamma knife radiosurgery in the management of cavernous sinus meningiomas

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 68-73 ◽  
Author(s):  
Pierre-Hugues Roche ◽  
Jean Régis ◽  
Henry Dufour ◽  
Henri-Dominique Fournier ◽  
Christine Delsanti ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Tumor Growth ◽  
Gamma Knife ◽  
Cavernous Sinus ◽  
Gamma Knife Radiosurgery ◽  
Surgical Removal ◽  
Content Type ◽  
Cavernous Sinus Meningioma ◽  
The Mean ◽  
Fine Print

Object. The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS). Methods. Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6–71 years). The mean tumor volume was 5.8 cm3 (range 0.9–18.6 cm3). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12–50 Gy), delivered with an average of eight isocenters (range two–18). The median peripheral isodose was 50% (range 30–70%). Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12–79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18 months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred. Conclusions. Gamma knife radiosurgery was found to be an effective low morbidity—related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas.

Gamma knife radiosurgery for craniopharyngiomas

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 47-56 ◽  
Author(s):  
Wen-Yuh Chung ◽  
David Hung-Chi Pan ◽  
Cheng-Ying Shiau ◽  
Wan-Yuo Guo ◽  
Ling-Wei Wang
Keyword(s):  
Clinical Outcome ◽  
Gamma Knife ◽  
Tumor Volume ◽  
Gamma Knife Radiosurgery ◽  
Tumor Control ◽  
Content Type ◽  
Stereotactic Aspiration ◽  
Cystic Component ◽  
The Mean ◽  
Fine Print

Object. The goal of this study was to elucidate the role of gamma knife radiosurgery (GKS) and adjuvant stereotactic procedures by assessing the outcome of 31 consecutive patients harboring craniopharyngiomas treated between March 1993 and December 1999. Methods. There were 31 consecutive patients with craniopharyngiomas: 18 were men and 13 were women. The mean age was 32 years (range 3–69 years). The mean tumor volume was 9 cm3 (range 0.3–28 cm3). The prescription dose to the tumor margin varied from 9.5 to 16 Gy. The visual pathways received 8 Gy or less. Three patients underwent stereotactic aspiration to decompress the cystic component before GKS. The tumor response was classified by percentage reduction of tumor volume as calculated based on magnetic resonance imaging studies. Clinical outcome was evaluated according to improvement and dependence on replacement therapy. An initial postoperative volume increase with enlargement of a cystic component was found in three patients. They were treated by adjuvant stereotactic aspiration and/or Ommaya reservoir implantation. Tumor control was achieved in 87% of patients and 84% had fair to excellent clinical outcome in an average follow-up period of 36 months. Treatment failure due to uncontrolled tumor progression was seen in four patients at 26, 33, 49, and 55 months, respectively, after GKS. Only one patient was found to have a mildly restricted visual field; no additional endocrinological impairment or neurological deterioration could be attributed to the treatment. There was no treatment-related mortality. Conclusions. Multimodality management of patients with craniopharyngiomas seemed to provide a better quality of patient survival and greater long-term tumor control. It is suggested that GKS accompanied by adjuvant stereotactic procedures should be used as an alternative in treating recurrent or residual craniopharyngiomas if further microsurgical excision cannot promise a cure.

Gamma knife radiosurgery for uveal melanomas: an 8-year experience

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 184-188 ◽  
Author(s):  
Gerald Langmann ◽  
Gerhard Pendl ◽  
Georg Papaefthymiou ◽  
Helmuth Guss ◽  
Keyword(s):  
Gamma Knife ◽  
Ciliary Body ◽  
Tumor Regression ◽  
Gamma Knife Radiosurgery ◽  
Neovascular Glaucoma ◽  
Content Type ◽  
Prescription Dose ◽  
The Mean ◽  
Fine Print ◽  
Uveal Melanomas

Object. The authors report their experience using gamma knife radiosurgery (GKS) to treat uveal melanomas. Methods. Between 1992 and 1998, 60 patients were treated with GKS at a prescription dose between 45 Gy and 80 Gy. The mean diameter of the tumor base was 12.2 mm (range 3–22 mm). The mean height of the tumor prominence was 6.7 mm (range 3–12 mm). The eye was immobilized. The follow-up period ranged from 16 to 94 months. Tumor regression was achieved in 56 (93%) of 60 patients. There were four recurrences followed by enucleation. The severe side effect of neovascular glaucoma developed in 21 (35%) patients in a high-dose group with larger tumors and in proximity to the ciliary body. A reduction in the prescription dose to 40 Gy or less and excluding treatment to tumors near the ciliary body decreased the rate of glaucoma without affecting the rate of tumor control. Conclusions. Gamma knife radiosurgery at a prescription dose of 45 Gy or more can achieve tumor regression in 85% of the uveal melanomas treated. Neovascular glaucoma can develop in patients when using this dose in tumors near the ciliary body. It is advised that such tumors be avoided and that the prescription dose be reduced to 40 Gy.

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