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https://www.readbyqxmd.com/read/28344466/an-overview-of-pharmacodynamic-modelling-ligand-binding-approach-and-its-application-in-clinical-practice
#1
REVIEW
Mohammed Saji Salahudeen, Prasad S Nishtala
The study of the magnitude and variation of drug response is defined as pharmacodynamics (PDs). PD models examine plasma concentration and effect relationship. It can predict the archetypal effect ([Formula: see text]) of a drug as a function of the drug concentration ([Formula: see text]) and estimate an unknown PD parameter ([Formula: see text]). The PD models have been described as fixed, linear, log-linear, [Formula: see text], sigmoid [Formula: see text], and indirect PD response. Ligand binding model is an example of a PD model that works on the underpinning PD principle of a drug, eliciting its pharmacological effect at the receptor site...
February 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28341442/risk-factors-for-postoperative-delirium-after-colorectal-operation
#2
Frederik J van der Sluis, Pieter L Buisman, Mark Meerdink, Wouter B Aan de Stegge, Boudewijn van Etten, Geertruida H de Bock, Barbara L van Leeuwen, Robert A Pol
BACKGROUND: A clear understanding of risk factors for postoperative delirium helps in the selection of individuals who might benefit from targeted perioperative intervention. The aim of this study was to identify risk factors for postoperative delirium after colorectal operation for malignancy. METHODS: All consecutive patients who underwent elective or emergency operation because of malignancy of the colon, sigmoid, or rectum between 2009 and 2012 were included in this study...
March 2017: Surgery
https://www.readbyqxmd.com/read/28340389/minilaparotomy-without-general-anesthesia-for-the-treatment-of-sigmoid-volvulus-in-high-risk-patients-a-case-series-of-4-patients
#3
Ernesto L Enrique, Kareem A Hamdy
BACKGROUND: Sigmoid volvulus (SV) is a common cause of large bowel obstruction worldwide. Presenting symptoms can be nonspecific and varied amongst the elderly population, making medical and surgical management challenging. This population is at markedly increase risk of complications and mortality with surgery under general anesthesia. In this case series, we describe 4 cases of sigmoid volvulus in octogenarians. GOALS: To demonstrate that sigmoid colectomy under local anesthesia, with or without intravenous conscious sedation, is feasible and can be done safely and with a low rate of converting to a general anesthetic...
March 2, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28340353/molecular-structure-of-the-human-cftr-ion-channel
#4
Fangyu Liu, Zhe Zhang, László Csanády, David C Gadsby, Jue Chen
The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of dephosphorylated human CFTR without nucleotides, determined by electron cryomicroscopy (cryo-EM). Close resemblance of this human CFTR structure to zebrafish CFTR under identical conditions reinforces its relevance for understanding CFTR function. The human CFTR structure reveals a previously unresolved helix belonging to the R domain docked inside the intracellular vestibule, precluding channel opening...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28339394/global-and-regional-assessment-of-sustained-inflation-pressure-volume-curves-in-patients-with-acute-respiratory-distress-syndrome
#5
Tobias Becher, Philipp Rostalski, Matthias Kott, Andy Adler, Dirk Schadler, Norbert Weiler, Inez Frerichs
Static or quasi-static pressure-volume (P-V) curves can be used to determine the lung mechanical properties of patients suffering from acute respiratory distress syndrome (ARDS). According to the traditional interpretation, lung recruitment occurs mainly below the lower point of maximum curvature (LPMC) of the inflation P-V curve. Although some studies have questioned this assumption, setting of positive end-expiratory pressure 2 cmH2O above the LPMC was part of a "lung-protective" ventilation strategy successfully applied in several clinical trials...
March 24, 2017: Physiological Measurement
https://www.readbyqxmd.com/read/28337676/logistic-proliferation-of-cells-in-scratch-assays-is-delayed
#6
Wang Jin, Esha T Shah, Catherine J Penington, Scott W McCue, Philip K Maini, Matthew J Simpson
Scratch assays are used to study how a population of cells re-colonises a vacant region on a two-dimensional substrate after a cell monolayer is scratched. These experiments are used in many applications including drug design for the treatment of cancer and chronic wounds. To provide insights into the mechanisms that drive scratch assays, solutions of continuum reaction-diffusion models have been calibrated to data from scratch assays. These models typically include a logistic source term to describe carrying capacity-limited proliferation; however, the choice of using a logistic source term is often made without examining whether it is valid...
March 23, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/28336491/neurobehavioral-effects-of-lithium-in-the-rat-investigation-of-the-effect-concentration-relationships-and-the-contribution-of-the-poisoning-pattern
#7
Anne-Sophie Hanak, Lucie Chevillard, Rodolphe Lebeau, Patricia Risède, Jean-Louis Laplanche, Nadia Benturquia, Bruno Mégarbane
Severity of lithium poisoning depends on the ingested dose, previous treatment duration and renal function. No animal study has investigated neurobehavioral differences in relation to the lithium poisoning pattern observed in humans, while differences in lithium pharmacokinetics have been reported in lithium-pretreated rats mimicking chronic poisonings with enhanced brain accumulation in rats with renal failure. Our objectives were: 1)-to investigate lithium-related effects in overdose on locomotor activity, anxiety-like behavior, spatial recognition memory and anhedonia in the rat; 2)-to model the relationships between lithium-induced effects on locomotion and plasma, erythrocyte, cerebrospinal fluid and brain concentrations previously obtained according to the poisoning pattern...
March 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28334867/the-silent-mutation-mlh1-c-543c-t-resulting-in-aberrant-splicing-can-cause-lynch-syndrome-a-case-report
#8
Tatsuro Yamaguchi, Tomokazu Wakatsuki, Mari Kikuchi, Shin-Ichiro Horiguchi, Kiwamu Akagi
The proband was a 67-year-old man with transverse and sigmoid colon cancer. Microsatellite instability analysis revealed a high frequency of microsatellite instability, and immunohistochemical staining showed the absence of both MLH1 and PMS2 proteins in the sigmoid colon cancer tissue specimens from the patient. DNA sequencing revealed a nucleotide substitution c.543C>T in MLH1, but this variant did not substitute an amino acid. The MLH1 c.543C>T variant was located 3 bases upstream from the end of exon 6 and created a new splice donor site 4 bases upstream from the end of exon 6...
March 1, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28333193/increased-activity-of-colistin-in-combination-with-amikacin-against-escherichia-coli-co-producing-ndm-5-and-mcr-1
#9
Yu-Feng Zhou, Meng-Ting Tao, Youjun Feng, Run-Shi Yang, Xiao-Ping Liao, Ya-Hong Liu, Jian Sun
Objectives: Colistin and carbapenem are two lines of last-resort antibiotics against lethal infections caused by MDR Gram-negative pathogens. The emergence of carbapenemase-positive Escherichia coli with colistin resistance poses a serious threat to public health worldwide. Here we report, for the first time (to the best of our knowledge), a novel combination therapy used for the treatment of E. coli co-producing MCR-1 and NDM-5. Methods: The MICs of colistin were determined alone and with 1-4 mg/L amikacin...
February 20, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28328936/polyp-detection-rate-in-transverse-and-sigmoid-colon-significantly-increases-with-longer-withdrawal-time-during-screening-colonoscopy
#10
Kazuhiro Kashiwagi, Nagamu Inoue, Toshifumi Yoshida, Rieko Bessyo, Kazuaki Yoneno, Hiroyuki Imaeda, Haruhiko Ogata, Takanori Kanai, Yoshinori Sugino, Yasushi Iwao
BACKGROUND: The guidelines for colonoscopy present withdrawal time (WT) and adenoma detection rate (ADR) as the quality indicator. The purpose of this retrospective study is to analyze the predicting factors with polyp detection rate (PDR) as a surrogate for ADR by using comprehensive health checkup data, and assess the correlation between PDR per each colonic segment and WT, and factors influencing WT. METHODS: One thousand and thirty six consecutive health checkup cases from April 2015 to March 2016 were enrolled in this study, and 880 subjects who undertook colonoscopy without polyp removal or biopsy were divided into the two groups (polyp not detected group vs polyp detected group)...
2017: PloS One
https://www.readbyqxmd.com/read/28327112/prognosis-of-ulcerative-colitis-colorectal-cancer-vs-sporadic-colorectal-cancer-propensity-score-matching-analysis
#11
Yoon Dae Han, Mahdi Hussain Al Bandar, Audrius Dulskas, Min Soo Cho, Hyuk Hur, Byung Soh Min, Kang Young Lee, Nam Kyu Kim
BACKGROUND: Ulcerative colitis (UC) harbours a high risk of UC-associated colorectal cancer (UCCC), which is important cause of morbidity and mortality in patients with inflammatory bowel disease. Overall Survival (OS) of patients with UCCC has not been addressed well in the literature. Thus, we compared oncologic outcome of UCCC and sporadic colorectal cancer (SCC) using propensity score matching analysis. METHODS: Propensity score matching was performed for 36 patients, a 1:1 matching method stratified into 18 in UCCC and 18 patients in SCC...
March 21, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28325716/coproporphyrin-i-a-fluorescent-endogenous-optimal-probe-substrate-for-abcc2-mrp2-that-is-suitable-for-vesicle-based-mrp2-inhibition-assay
#12
Ravindranath Reddy Gilibili, Sagnik Chatterjee, Pravin Bagul, Kthleen W Mosure, Bokka Venkata Murali, T Thanga Mariappan, Sandhya Mandlekar, Yurong Lai
Inside-out-oriented membrane vesicles are useful tools to investigate whether a compound can be an inhibitor of efflux transporters such as multidrug-resistance associated protein 2 (MRP2). However, because of technical limitations of substrate diffusion and low dynamic uptake windows for interacting drugs used in clinic, estradiol-17β-glucuronide (E17βG) remains the probe substrate frequently used in MRP2 inhibition assays. Here we re-capitulated the sigmoidal kinetics of MRP2 mediated uptake of E17βG, with apparent Km and Vmax values 170 ±17 μM and 1447 ± 137 pmol/mg protein/min, respectively...
March 21, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28325052/-colorectal-cancer-the-importance-of-primary-tumor-location
#13
M Ryska, J Bauer
Retrospective evaluations of the relevance of primary colorectal cancer (CRC) location consistently indicate that right-sided tumors, arising in the cecum, ascending colon, hepatic bend, transverse colon and splenic flexure, are clinically, biologically and genetically different from left-sided tumors - those located in the descending colon, sigmoid colon or rectum. Location in the right-sided colon represents a negative prognostic indicator, particularly for stage III and IV carcinomas. Irrespective of treatment, the rightward location is associated with a significantly increased risk of death when compared to the left side...
2017: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
https://www.readbyqxmd.com/read/28323221/laparoscopic-promontohysteropexy-during-pregnancy
#14
L Pirtea, O Balint, C Secosan, R Ilina, D Grigoras
STUDY OBJECTIVE: to present a case of uterine prolapse in a 10 weeks pregnant patient that was successfully treated by laparoscopic promontohysteropexy. To our knowledge, this is the first case of laparoscopic promontopexy during pregnancy to ever be reported in literature. DESIGN: step by step explanation of the surgery using video SETTING: Uterine prolapse is a rare condition in young patients and extremely are in pregnant women. The incidence of uterine prolapse during pregnancy reported in literature is 1 per 10...
March 17, 2017: Journal of Minimally Invasive Gynecology
https://www.readbyqxmd.com/read/28323157/anatomic-variations-of-inferior-mesenteric-artery-and-left-colic-artery-evaluated-by-3-dimensional-ct-angiography-insights-into-rectal-cancer-surgery
#15
Jia Ke, Jiawei Cai, Xiaofeng Wen, Xianrui Wu, Zhen He, Yifeng Zou, Jianping Qiu, Xiaowen He, Xiaosheng He, Lei Lian, Xiaojian Wu, Zhiyang Zhou, Ping Lan
OBJECTIVE: To demonstrate the clinical applicability of 3-dimensional CT angiography (3D-CTA) in evaluating the anatomic variations of inferior mesenteric artery (IMA) and left colic artery (LCA), to help make pre-operative strategies of rectal cancer surgery. METHODS: 188 patients with abdominal and pelvic contrast-enhanced CT scan were retrospectively enrolled and 3D-CTA was reconstructed. The origin and branching patterns of IMA, tracking patterns of LCA, intersectional patterns among IMA, LCA and inferior mesenteric vein (IMV) were examined, and their associations with clinical features were analyzed...
March 16, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28322898/biliary-stent-migration-a-rare-cause-of-a-bladder-stone
#16
Neha R Malhotra, Carlos Amir Esparza Monzavi, Jean-Sebastien Trepanier, Johan Nordenstam, Michael R Abern
Our patient presented with dysuria and pneumaturia without any prior urologic instrumentation. History included choledocolithiasis requiring ERCP and biliary stenting. Imaging showed a large bladder stone. She was taken to surgery and found to have diverticulitis. The sigmoid was resected and the bladder found to have a small fistula tract. The bladder was opened and a large calculus was identified and extracted. The stone was opened and found to contain a biliary stent. While biliary stenting is generally considered safe, migration can occur...
March 17, 2017: Urology
https://www.readbyqxmd.com/read/28319760/improved-prediction-of-higher-heating-value-of-biomass-using-an-artificial-neural-network-model-based-on-proximate-analysis
#17
Harun Uzun, Zeynep Yıldız, Jillian L Goldfarb, Selim Ceylan
As biomass becomes more integrated into our energy feedstocks, the ability to predict its combustion enthalpies from routine data such as carbon, ash, and moisture content enables rapid decisions about utilization. The present work constructs a novel artificial neural network model with a 3-3-1 tangent sigmoid architecture to predict biomasses' higher heating values from only their proximate analyses, requiring minimal specificity as compared to models based on elemental composition. The model presented has a considerably higher correlation coefficient (0...
March 9, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28319420/modelling-long-term-evolution-of-chitotriosidase-in-non-neuronopathic-gaucher-disease
#18
Cristina Drugan, Tudor C Drugan, Paula Grigorescu-Sido, Ioana Naşcu
Chitotriosidase, an enzyme secreted by activated macrophages, is widely used as a biomarker for therapeutic monitoring and patient follow-up in Gaucher disease (GD), a lysosomal disorder caused by an inherited deficiency of glucocerebrosidase. We analyzed the long-term evolution of chitotriosidase aiming to establish an accurate model that describes the influence of enzyme replacement therapy (ERT) and the impact of several covariates. A total of 55 patients with non-neuronopathic (type 1) GD were followed for almost 17 years (during a maximum of 7...
March 20, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28316870/dural-arteriovenous-fistula-manifested-as-rapid-progressive-dementia-successfully-treated-by-endovascular-embolization-only
#19
Heewon Hwang, Yun Kyung La, Min Seok Baek, Kyoungwon Baik, Sang Hyun Suh, Won-Joo Kim
A 43-year-old male presented with daytime sleepiness at work and indifferent behavior like never before. Two weeks prior to hospital admission, he had episodic memory loss with well preserved remote memory. Brain MRI showed a dural arteriovenous fistula (DAVF) in the right lateral transverse sinus with a bilateral thalamic venous infarction. Cerebral angiography confirmed a right transverse sigmoid dural arteriovenous fistula with a feeding artery of the right occipital artery and left posterior meningeal artery...
March 2017: Neurointervention
https://www.readbyqxmd.com/read/28303363/test-retest-reliability-of-scotopic-full-field-electroretinograms-in-rabbits
#20
Jan Luebke, Alexandra Anton, Michael Bach
PURPOSE: To explore test-retest reliability of standard scotopic full-field ERG measurements in New Zealand White rabbits. The ERG is widely used for testing of retinal integrity after any ocular treatment. We here present detailed stimulus-response dependencies for single healthy and untreated animals, concentrating on test-retest reproducibility. MATERIALS AND METHODS: Five New Zealand White rabbits (aged 8-10 weeks, weight about 2.0-2.5 kg) underwent binocular ERG measurements after intramuscular anesthesia and pharmaceutical pupillary dilatation at a baseline day and 10 days later...
March 16, 2017: Documenta Ophthalmologica. Advances in Ophthalmology
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