Intracellular Concentration Gradients That Mirror External Gradients in Microfluidic Flows: A Computational Analysis

Abstract

The generation of stable intracellular concentration gradients is a useful method for local control of cell function, selective manipulation of cellular structures and testing hypotheses related to dynamical intracellular processes. Cell culture in a microfluidic device allows the presentation of a stable gradient of small molecules across a single cell. This method has been used to selectively label mitochondria in portions of the cell, trypsinize specific cellular domains, and trigger receptor-mediated endocytosis in specific portions of the cell. Given the small length scales of a typical cell (~30 μm) and short cytoplasmic diffusive time scales of small molecules, it is surprising that cells can be labeled locally with this method. Here we developed models to explore the parametric space over which stable intracellular concentration gradients can be maintained in a microfluidic device. We show that gradients can develop and be maintained indefinitely for high rates of mass transfer across the membrane compared with diffusion, that is, for Sherwood number greater than 1. We show how these gradients can result in gradients in ligand–receptor binding and enzyme substrate binding. This analysis can help interpret and design microfluidic experiments for cytoplasmic partitioning.

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CT-perfusion measurements in pancreatic carcinoma with different kinetic models: Is there a chance for tumour grading based on functional parameters?

Abstract

Background

To evaluate the interchangeability of perfusion parameters obtained with help of models used for post-processing of perfusion-CT images in pancreatic adenocarcinoma and to determine the mean values and ranges of perfusion in different tumour gradings.

Methods

Perfusion-CT imaging was performed prospectively in 48 consecutive patients with pancreatic adenocarcinoma. In 42 patients biopsy-proven tumor grading was available (4 × G1/24 × G2/14 × G3/6× unknown). Images were post-processed using a model based on the maximum-slope (MS) approach (blood flow-BFMS) + Patlak analysis (P) (blood volume [BVP] and permeability [k-transP]), as well as a model with deconvolution-based (D) analysis (BFD, BVD and k-transD). 50 mL contrast agent were applied with a delay time of 7 s. Perfusion parameters were compared using intraclass correlation coefficient (ICC), the Wilcoxon matched-pairs test and Bland-Altman plots.

Results

Forty eight VOIs of tumours were outlined and analysed. Moderate to good ICC values were found for the perfusion parameters (ICC = 0.62–0.75). Wilcoxon matched-pairs revealed significantly lower values (P < .001 and 0.008), for the BF and BV values obtained using the maximum-slope approach + Patlak analysis compared to deconvolution based analysis. For k-trans measurement, deconvolution revealed significantly lower values (P < 0.001). Different histologic subgroups (G1-G3) did not show significantly different functional parameters.

Conclusion

There were significant differences in the perfusion parameters obtained using the different calculation methods, and therefore these parameters are not directly interchangeable. However, the magnitude of pairs of parametric values is in constant relation to each other enabling the use of any of these methods. VPCT parameters did not allow for histologic classification.

http://ift.tt/2hExnJP

Auslöser von Arzneiexanthemen: Absetzen, durchbehandeln oder desensibilisieren?

Zusammenfassung

Arzneimittelüberempfindlichkeitsreaktionen betreffen über 7% der Bevölkerung und sind ein Problem für Patienten und Ärzte. Viele solcher Reaktionen treten in Form von Arzneimittelexanthemen auf. Klinische Manifestationen von Arzneimittelexanthemen sind sehr variabel und reichen von einem lokalisierten fixen Arzneimittelexanthem zu lebensbedrohlichen schweren bullösen oder systemischen Überempfindlichkeitsreaktionen. Entsprechend dem hier vorgeschlagenen Algorithmus sollte bei Verdacht auf ein Arzneimittelexanthem zunächst eine Kausalitätsprüfung erfolgen. Wenn sowohl der zeitliche Ablauf als auch die klinische Manifestation für ein Arzneimittelexanthem sprechen, ist das auslösende Arzneimittel zu meiden. Nur bei dringender Therapieindikation, fehlenden alternativen Arzneimitteln und nach sorgfältiger, individueller Risiko-Nutzen-Analyse sollte eine Durchbehandlung oder eine Toleranzinduktion durch „Desensibilisierung" erwogen werden.

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Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation in men

Abstract

Phenylephrine increases mean arterial pressure (MAP) by enhanced total peripheral resistance (TPR) but near-infrared spectroscopy (NIRS) determined muscle oxygenation (S_mO₂) increases. We addressed that apparent paradox during supine rest and head-up tilt (HUT). Variables were determined ± phenylephrine in males during supine rest (n = 17) and 40° HUT (n = 7). MAP, stroke volume (SV), heart rate (HR), and TPR were derived by Modelflow^® and NIRS determined biceps S_mO₂ and (tibial) bone oxygenation (S_tibialO₂). For ten subjects, cardiac filling and the diameter of the inferior caval vein (ICV collapsibility index: ((ICV_expiration − ICV_inspiration)/ICV_expiration) × 100) were assessed by ultrasound. Pancreatic polypeptide (PP) and atrial natriuretic peptide (proANP) in plasma were determined by immunoassay. Brachial artery blood flow was assessed by ultrasound and skin oxygenation (S_skinO₂) monitored by white light spectroscopy. Phenylephrine increased MAP by 34% and TPR (62%; P < 0.001) during supine rest. The ICV collapsibility index decreased (24%; P < 0.001) indicating augmented cardiac preload although volume of the left atrium and ventricle did not change. SV increased (18%; P < 0.001) as HR decreased (24%; P < 0.001). ProANP increased by 9% (P = 0.002) with unaffected PP. Brachial artery blood flow tended to decrease while S_skinO₂ together with S_tibialO₂ decreased by 11% (P = 0.026) and 20% (P < 0.001), respectively. Conversely, phenylephrine increased S_mO₂ (9%) and restored the HUT elicited decrease in S_mO₂ (by 19%) along with SV (P = 0.02). Phenylephrine reduces skin and bone oxygenation and tends to reduce arm blood flow, suggesting that the increase in S_mO₂ reflects veno-constriction with consequent centralization of the blood volume.

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Systemic air embolism during pleural lavage for empyema

Abstract

Pleural lavage has been considered a convenient and safe method that is often performed for empyema. We report a case of systemic air embolism that developed during pleural lavage. A 53-year-old man with empyema in the organizing phase suddenly developed paralysis of the left side of the body and altered level of consciousness during pleural lavage, which was performed in a sitting position without negative pressure suction. Systemic air embolism was diagnosed based on computed tomography. In this case, use of fibrinolytic agents, positioning during pleural lavage, and pressure in an empyema cavity may have predisposed to development of systemic air embolism. Conversion from thoracoscopic therapy to open decortication or fenestration should be considered to prevent this type of complication.

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A Statewide Quality Improvement Initiative to Reduce Non-Medically Indicated Scheduled Deliveries

Abstract

Objectives To evaluate a large two-phase, statewide quality improvement (QI) collaborative to decrease non-medically indicated (N-MI) deliveries scheduled between 36 and 38 weeks gestation (early). Methods The New York State Department of Health (NYSDOH) convened a Perinatal Quality Collaborative to devise a two-phase QI initiative using a rapid cycle incremental learning model. Phase 1 included Regional Perinatal Centers (RPCs), and Phase 2 added their affiliated perinatal hospitals. Maternal demographics, delivery characteristics, medical indications, and stillbirths were collected on scheduled inductions and cesarean section (CS) deliveries between 36 and 38 weeks. Results There were 35,091 scheduled 36–38 week deliveries reported during the collaborative's 4 years. The percentage of early N-MI scheduled deliveries decreased 41-fold in RPCs (Phase 1 and Phase 2), and 17-fold in affiliates (Phase 2). There was a significant statewide increase in deliveries at ≥39 weeks (P < 0.001), with an estimated 23,732 early deliveries averted. Stillbirths did not increase over time (P = 0.42), although reporting was incomplete. Conclusions A two-phase, statewide QI collaborative in a large state with regionalized perinatal care effectively lowered the number of N-MI deliveries scheduled between 36 and 38 weeks gestation. Associated improvements in neonatal and early childhood developmental outcomes should translate to significant cost savings. This model can effectively be used for similar as well as other obstetrical QI.

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Ultrasound follow-up of an unusual giant urinoma in a newborn

Abstract

Urinoma, defined as an encapsulation of urine caused by urine extravasation into the perirenal space either through rupture of a calyceal fornix or a tear in the renal parenchyma, is an uncommon finding in prenatal diagnosis and the neonatal period. Urinoma can be associated with any urinary tract obstruction, or, as reported in several published cases, related to vesicoureteral reflux, kidney dysplasia, or complication arising during amniocentesis. We report on a newborn with a perinatal urinoma, with initial slight corpusculated fluid associated with nonobstructive and nonrefluxing megaureter, and no signs of kidney dysplasia. Close sonography follow-up of the urinoma allowed complex differential diagnoses, including cystic, septated, and solid perirenal masses, due to dissimilar and peculiar ultrasound images during urinoma evolution stages.

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