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1.
J Clin Anesth ; 78: 110673, 2022 06.
Article in English | MEDLINE | ID: mdl-35134618

ABSTRACT

STUDY OBJECTIVE: Quantitative neuromuscular monitoring is traditionally evaluated at the adductor pollicis muscle. By contrast, the TOF-Cuff compressomyograph evaluates neuromuscular block (NMB) at the upper arm. However, compressomyography has not been fully validated against other monitoring entities. This study evaluates the agreement between NMB measured by compressomyography at the upper arm and electromyography at the adductor pollicis muscle during various levels of neuromuscular block in patients with and without obesity. INTERVENTIONS: NMB was measured at the upper arm by compressomyography (TOF-Cuff) and by electromyography (GE-NMT) at the adductor pollicis. DESIGN: Prospective, multicenter, observational study. SETTING: Secondary and tertiary care hospitals' operating theatres. PATIENTS: 200 non-obese and 50 obese patients. MEASUREMENTS: During onset and offset of deep (post-tetanic-count 1-15 twitches), moderate (Train-of-Four-count 1-3 twitches) and shallow (Train-of-Four-ratio 0.01-1.0) depths of NMB were measured in obese and non-obese patients. The bias and limits of agreement of both devices were calculated using a Bland-Altman analysis for repeated measurements. Data obtained during spontaneous recovery (i.e. without the use of reversal agents) were used in the primary analyses. MAIN RESULTS: Data from enrolled patients yielded 942 paired post-tetanic-counts, 1175 paired train-of-four-counts and 1574 paired train-of-four ratios during spontaneous recovery. In non-obese patients, mean bias (95% CI) between the two devices was 3.405 (2.294 to 4.517) during deep NMB; -0.023 (-0.205 to 0.160) during moderate NMB and 0.312 (0.287 to 0.338) during shallow NMB. In obese patients, bias was -0.170 (-2.872 to 2.531); 0.178 (-0.202 to 0.558); 0.384 (0.299 to 0.469) for deep, moderate and shallow NMB respectively. CONCLUSIONS: There is variable disagreement between the level of NMB measured at the upper arm by compressomyography and at the adductor pollicis muscle measured by electromyography, throughout the various stages of NMB in obese and non-obese patients. Recovery of NMB on compressomyography preceded recovery on electromyography, which may have consequences for reversal and extubation decisions in clinical practice.


Subject(s)
Neuromuscular Blockade , Neuromuscular Nondepolarizing Agents , Arm , Electromyography , Humans , Muscle, Skeletal , Obesity/complications , Prospective Studies
2.
J Mater Chem B ; 9(46): 9575-9582, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34766964

ABSTRACT

In this article, we present a facile and robust method for the surfactant-free preparation of polynorepinephrine stabilised microcapsules templated from an oil-in-water emulsion. The resulting microcapsule structures are dependent on the concentration of Cu2+ used to catalyse norepinephrine polymerisation. When the concentration of Cu2+ increases, the diameter of the microcapsules and the thickness of the shell increase correspondingly. The mechanical and chemical stability provided by the polynorepinephrine shell are explored using surface pressure measurements and atomic force microscopy, demonstrating that a rigid and robust polynorepinephrine shell is formed. In order to demonstrate potential application of the microcapsules in sustained release, Nile red stained squalane was encapsulated, and pH responsive release was monitored. It was seen that by controlling pH, the release profile could be controlled, with highest release efficacy achieved in alkaline conditions, offering a new pathway for development of encapsulation systems for the delivery of water insoluble actives.


Subject(s)
Nanocomposites/chemistry , Norepinephrine/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Capsules/chemical synthesis , Cell Line, Tumor , Drug Delivery Systems , Emulsions/chemistry , Escherichia coli/drug effects , Humans , Hydrogels/chemical synthesis , Hydrogen-Ion Concentration , Neoplasm Recurrence, Local/drug therapy , Polyethylene Glycols/chemistry , Skin Neoplasms , Staphylococcus aureus/drug effects , Tissue Engineering , Wound Healing
3.
Radiat Oncol ; 16(1): 37, 2021 Feb 19.
Article in English | MEDLINE | ID: mdl-33608008

ABSTRACT

BACKGROUND: The benefit of MR-only workflow compared to current CT-based workflow for prostate radiotherapy is reduction of systematic errors in the radiotherapy chain by 2-3 mm. Nowadays, MRI is used for target delineation while CT is needed for position verification. In MR-only workflows, MRI based synthetic CT (sCT) replaces CT. Intraprostatic fiducial markers (FMs) are used as a surrogate for the position of the prostate improving targeting. However, FMs are not visible on sCT. Therefore, a semi-automatic method for burning-in FMs on sCT was developed. Accuracy of MR-only workflow using semi-automatically burned-in FMs was assessed and compared to CT/MR workflow. METHODS: Thirty-one prostate cancer patients receiving radiotherapy, underwent an additional MR sequence (mDIXON) to create an sCT for MR-only workflow simulation. Three sources of accuracy in the CT/MR- and MR-only workflow were investigated. To compare image registrations for target delineation, the inter-observer error (IOE) of FM-based CT-to-MR image registrations and soft-tissue-based MR-to-MR image registrations were determined on twenty patients. Secondly, the inter-observer variation of the resulting FM positions was determined on twenty patients. Thirdly, on 26 patients CBCTs were retrospectively registered on sCT with burned-in FMs and compared to CT-CBCT registrations. RESULTS: Image registration for target delineation shows a three times smaller IOE for MR-only workflow compared to CT/MR workflow. All observers agreed in correctly identifying all FMs for 18 out of 20 patients (90%). The IOE in CC direction of the center of mass (COM) position of the markers was within the CT slice thickness (2.5 mm), the IOE in AP and RL direction were below 1.0 mm and 1.5 mm, respectively. Registrations for IGRT position verification in MR-only workflow compared to CT/MR workflow were equivalent in RL-, CC- and AP-direction, except for a significant difference for random error in rotation. CONCLUSIONS: MR-only workflow using sCT with burned-in FMs is an improvement compared to the current CT/MR workflow, with a three times smaller inter observer error in CT-MR registration and comparable CBCT registration results between CT and sCT reference scans. Trial registry Medical Research Involving Human Subjects Act (WMO) does apply to this study and was approved by the Medical Ethics review Committee of the Academic Medical Center. Registration number: NL65414.018.18. Date of registration: 21-08-2018.


Subject(s)
Fiducial Markers , Magnetic Resonance Imaging/methods , Prostatic Neoplasms/radiotherapy , Radiotherapy, Image-Guided/methods , Workflow , Humans , Male , Observer Variation , Radiotherapy Planning, Computer-Assisted , Tomography, X-Ray Computed
4.
J Cyst Fibros ; 19(4): 562-568, 2020 07.
Article in English | MEDLINE | ID: mdl-32335023

ABSTRACT

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback. METHODS: A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module). RESULTS: One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p< 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p < 0.001). CONCLUSIONS: The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms.


Subject(s)
Cystic Fibrosis , Enzyme Replacement Therapy/methods , Exocrine Pancreatic Insufficiency , Gastrointestinal Diseases , Mobile Applications , Quality of Life , Self-Management/methods , Abdominal Pain/etiology , Abdominal Pain/therapy , Child , Cystic Fibrosis/physiopathology , Cystic Fibrosis/psychology , Cystic Fibrosis/therapy , Exocrine Pancreatic Insufficiency/etiology , Exocrine Pancreatic Insufficiency/therapy , Female , Gastrointestinal Diseases/etiology , Gastrointestinal Diseases/physiopathology , Gastrointestinal Diseases/psychology , Gastrointestinal Diseases/therapy , Humans , Malabsorption Syndromes/etiology , Malabsorption Syndromes/therapy , Male , Malnutrition/etiology , Malnutrition/therapy , Surveys and Questionnaires
5.
J Sep Sci ; 43(7): 1256-1264, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32012437

ABSTRACT

Process streams of agro-food industries are often large and viscous. In order to fractionate such a stream the viscosity can be reduced by either a high temperature or dilution, the former is not an option in case of temperature sensitive components. Such streams are diluted prior to chromatographic fractionation, resulting in even larger volumes and high energy costs for sub-sequential water removal. The influence of feed viscosity on the performance of simulated moving bed chromatography has been investigated in a case study of the recovery of a γ-aminobutyric acid rich fraction from tomato serum. This work addresses the chromatographic system design, evaluates results from a pilot scale operation, and uses these to calculate the productivity and water use at elevated feed concentration. At the two higher feed viscosities (2.5 and 4 mPa·s) water use is lower and productivity higher, compared to the lowest feed viscosity (1 mPa·s). The behavior of the sugars for different feed viscosities can be described well by the model using the ratio of feed to eluent as dilution factor. The behavior of γ-aminobutyric acid is highly concentration dependent and the recovery could not be accurately predicted.


Subject(s)
Solanum lycopersicum/chemistry , gamma-Aminobutyric Acid/isolation & purification , Viscosity , gamma-Aminobutyric Acid/chemistry
6.
J Chromatogr A ; 1613: 460688, 2020 Feb 22.
Article in English | MEDLINE | ID: mdl-31813564

ABSTRACT

Diffusion inside pores is the rate limiting step in many preparative chromatographic separations and a key parameter for process design in weak interaction aqueous chromatographic separations employed in food and bio processing. This work aims at relating diffusion inside porous networks to properties of stationary phase and of diffusing molecules. Intraparticle diffusivities were determined for eight small molecules in nine different stationary phases made from three different backbone materials. Measured intraparticle diffusivities were compared to the predictive capability of the correlation by Mackie and Meares and the parallel pore model. All stationary phases were analyzed for their porosity, apparent pore size distribution and tortuosity, which are input parameters for the models. The parallel pore model provides understanding of the occurring phenomena, but the input parameters were difficult to determine experimentally. The model predictions of intraparticle diffusion were of limited accuracy. We show that prediction can be improved when combining the model of Mackie and Meares with the fraction of accessible pore volume. The accessible pore volume fraction can be determined from inverse size exclusion chromatographic measurements. Future work should further challenge the improved model, specifically widening the applicability to greater accessible pore fractions (> 0.7) with corresponding higher intraparticle diffusivities (Dp/Dm  > 0.2). A database of intraparticle diffusion and stationary phase pore property measurements is supplied, to contribute to general understanding of the relationship between intraparticle diffusion and pore properties.


Subject(s)
Chromatography, Gel , Diffusion , Models, Chemical , Porosity
7.
Expert Opin Drug Saf ; 18(10): 883-891, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31359807

ABSTRACT

Introduction: Sugammadex is a modified cyclodextrin that is able to reverse neuromuscular block induced by aminosteroidal neuromuscular blocking drugs. Compared to reversal with neostigmine, it reverses neuromuscular block quicker and more predictable and without cholinergic side effects. However, there have been concerns about sugammadex ability to bind other drugs and its effects on QT interval and clotting times. In addition, sugammadex might induce hypersensitivity reactions more frequently than initially anticipated. This review summarizes current evidence with regard to these and other safety aspects of sugammadex. Areas covered: This review provides an overview of the efficacy of sugammadex in various patient populations, evaluates potential interactions with other drugs and discusses adverse effects and reactions that have been reported in the literature. Expert opinion: Sugammadex quickly reverses aminosteroid neuromuscular block with less side effects compared to neostigmine. As such, it has the potential to significantly reduce the incidence of residual neuromuscular block and to improve postoperative pulmonary outcome. Current safety concerns mainly focus on hypersensitivity reactions and cardiac arrhythmias. Although the absolute risk for these events is low, ongoing vigilance and research in this area are needed.


Subject(s)
Neostigmine/administration & dosage , Neuromuscular Nondepolarizing Agents/antagonists & inhibitors , Sugammadex/administration & dosage , Cholinesterase Inhibitors/administration & dosage , Cholinesterase Inhibitors/adverse effects , Humans , Neostigmine/adverse effects , Neuromuscular Blockade , Sugammadex/adverse effects , Sugammadex/pharmacology
9.
Brain ; 142(3): 542-559, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30668673

ABSTRACT

Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug discovery.


Subject(s)
Epilepsy/etiology , Proteins/genetics , Proteins/metabolism , Animals , Disease Models, Animal , Epilepsy/physiopathology , Female , HEK293 Cells , Humans , Male , Phenotype , Pyridoxal Phosphate/therapeutic use , Pyridoxine/deficiency , Vitamin B 6/metabolism , Vitamin B 6 Deficiency/genetics , Vitamin B 6 Deficiency/metabolism , Zebrafish
10.
Adv Healthc Mater ; 7(12): e1800184, 2018 06.
Article in English | MEDLINE | ID: mdl-29696808

ABSTRACT

The efficient penetration of drugs into tumors is a major challenge that remains unmet. Reported herein is a strategy to promote extravasation and enhanced penetration using inertial cavitation initiated by focused ultrasound and cone-shaped gold nanoparticles that entrap gas nanobubbles. The cones are capable of initiating inertial cavitation under pressures and frequencies achievable with existing clinical ultrasound systems and of promoting extravasation and delivery of a model large therapeutic molecule in an in vitro tissue mimicking flow phantom, achieving penetration depths in excess of 2 mm. Ease of functionalization and intrinsic imaging capabilities provide gold with significant advantages as a material for biomedical applications. The cones show neither cytotoxicity in Michigan Cancer Foundation (MCF)-7 cells nor hemolytic activity in human blood at clinically relevant concentrations and are found to be colloidally stable for at least 5 d at 37 °C and several months at 4 °C.


Subject(s)
Drug Delivery Systems/methods , Gold , Metal Nanoparticles , Neoplasms/drug therapy , Ultrasonic Waves , Gold/chemistry , Gold/pharmacology , Humans , MCF-7 Cells , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use , Neoplasms/metabolism , Neoplasms/pathology
11.
J Neurol ; 265(6): 1310-1319, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29569176

ABSTRACT

INTRODUCTION: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. METHODS: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. RESULTS: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28-84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). CONCLUSION: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted.


Subject(s)
Central Nervous System Diseases/epidemiology , Demyelinating Diseases/epidemiology , Adolescent , Central Nervous System Diseases/therapy , Child , Child, Preschool , Demyelinating Diseases/therapy , Female , Follow-Up Studies , Humans , Incidence , Male , Netherlands/epidemiology , Prospective Studies
12.
Int J Obes (Lond) ; 42(2): 260-269, 2018 02.
Article in English | MEDLINE | ID: mdl-28852207

ABSTRACT

BACKGROUND/OBJECTIVES: In obesity, B cells accumulate in white adipose tissue (WAT) and produce IgG, which may contribute to the development of glucose intolerance. IgG signals by binding to Fcγ receptors (FcγR) and by activating the complement system. The aim of our study was to investigate whether activation of FcγR and/or complement C3 mediates the development of high-fat diet-induced glucose intolerance. METHODS: We studied mice lacking all four FcγRs (FcγRI/II/III/IV-/-), only the inhibitory FcγRIIb (FcγRIIb-/-), only the central component of the complement system C3 (C3-/-), and mice lacking both FcγRs and C3 (FcγRI/II/III/IV/C3-/-). All mouse models and wild-type controls were fed a high-fat diet (HFD) for 15 weeks to induce obesity. Glucose metabolism was assessed and adipose tissue was characterized for inflammation and adipocyte functionality. RESULTS: In obese WAT of wild-type mice, B cells (+142%, P<0.01) and IgG (+128% P<0.01) were increased compared to lean WAT. Macrophages of FcγRI/II/III/IV-/-mice released lower levels of cytokines compared to wild-type mice upon IgG stimulation. Only C3-/- mice showed reduced HFD-induced weight gain as compared to controls (-18%, P<0.01). Surprisingly, FcγRI/II/III/IV-/- mice had deteriorated glucose tolerance (AUC +125%, P<0.001) despite reduced leukocyte number (-30%, P<0.05) in gonadal WAT (gWAT), whereas glucose tolerance and leukocytes within gWAT in the other models were unaffected compared to controls. Although IgG in gWAT was increased (+44 to +174%, P<0.05) in all mouse models lacking FcγRIIb, only FcγRI/II/III/IV/C3-/- mice exhibited appreciable alterations in immune cells in gWAT, for example, increased macrophages (+36%, P<0.001). CONCLUSIONS: Lack of FcγRs reduces the activity of macrophages upon IgG stimulation, but neither FcγR nor C3 deficiency protects against HFD-induced glucose intolerance or reduces adipose tissue inflammation. This indicates that if obesity-induced IgG contributes to the development of glucose intolerance, this is not mediated by FcγR or complement activation.


Subject(s)
Adipose Tissue, White/metabolism , Complement C3/metabolism , Glucose Intolerance/metabolism , Inflammation/metabolism , Obesity/metabolism , Receptors, IgG/metabolism , Animals , Cells, Cultured , Diet, High-Fat , Disease Models, Animal , Inflammation/physiopathology , Male , Mice , Mice, Knockout , Obesity/physiopathology
13.
Sci Rep ; 7(1): 14657, 2017 11 07.
Article in English | MEDLINE | ID: mdl-29116124

ABSTRACT

Patients with Primary Ciliary Dyskinesia (PCD) suffer from recurrent upper and lower airway infections due to defects in the cilia present on the respiratory epithelium. Since chronic inflammatory conditions can cause changes in innate immune responses, we investigated whether monocytes isolated from the peripheral blood of pediatric PCD patients respond differently to inflammatory stimuli, compared to monocytes from healthy children and adults. The receptor for C5a (C5aR) was upregulated in PCD, whereas expression levels of the leukocyte chemoattractant receptors CCR1, CCR2, CCR5, BLT1 and FPR1 on PCD monocytes were similar to those on monocytes from healthy individuals. Also in vitro migration of PCD monocytes towards the ligands of those receptors (CCL2, fMLP, C5a and LTB4) was normal. Compared to healthy children, PCD patients had a higher percentage of the non-classic monocyte subset (CD14+CD16++) in circulation. Finally, PCD monocytes produced higher levels of pro-inflammatory cytokines (IL-1ß and TNF-α) and chemokines (CCL3, CCL5, CCL18 and CCL22) in response to LPS, peptidoglycan and/or dsRNA stimulation. These data suggest that monocytes might exacerbate inflammatory reactions in PCD patients and might maintain a positive feedback-loop feeding the inflammatory process.


Subject(s)
Ciliary Motility Disorders/metabolism , Cytokines/metabolism , Monocytes/metabolism , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Ciliary Motility Disorders/pathology , Female , Humans , Inflammation/metabolism , Inflammation/pathology , L-Selectin/metabolism , Lewis X Antigen/metabolism , Male , Monocytes/pathology , Phagocytosis , Receptor, Anaphylatoxin C5a/metabolism , Young Adult
15.
Eur J Paediatr Neurol ; 21(6): 912-920, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28757335

ABSTRACT

The autosomal dominant progeroid form of cutis laxa is a recently identified multiple congenital anomaly disorder characterized by thin, wrinkled skin, a progeroid appearance, intra-uterine growth retardation, postnatal growth restriction, psychomotor developmental delay, microcephaly, cataract, hypotonia and contractures. De novo heterozygous mutations in ALDH18A1 have been described in this condition. We present neuroimaging abnormalities in three patients. One patient had intracranial arterial and venous tortuosity, widened ventricular and extra-axial cerebrospinal fluid (CSF) spaces, wide perivascular spaces and increased T2 signal intensity in the cerebral white matter over time. The second patient had vascular tortuosity. The third patient had prominent ventricular and extra-axial cerebrospinal fluid (CSF) spaces on CT. We propose an embryological mechanism for the development of intracranial vascular tortuosity and discuss the anatomical basis of wide perivascular spaces in relation to this syndrome. Although we do not know the clinical implications of these cerebral vascular anomalies, we suggest inclusion of neuroimaging in the baseline evaluation of these patients.


Subject(s)
Brain/diagnostic imaging , Brain/pathology , Cutis Laxa/diagnostic imaging , Cutis Laxa/pathology , Aldehyde Dehydrogenase/genetics , Cutis Laxa/genetics , Female , Humans , Infant , Male , Mutation , Neuroimaging/methods , Syndrome
16.
J Chromatogr A ; 1493: 49-56, 2017 Apr 14.
Article in English | MEDLINE | ID: mdl-28318565

ABSTRACT

In industrial liquid separation processes chromatography often has a key function in the optimization of yield and purity. For the design of an industrial system, chromatographic processes are generally simulated using mathematical models, tested and optimized at laboratory level, and then scaled up to pilot and subsequently industrial scale. To describe the system, experimental data and model data need to be fitted and extra column contribution must be determined. This paper describes the influence of extra-column volume on overall separation efficiency for lab scale and its impact on the design of large scale systems. Measurement of extra-column contribution was investigated in terms of mean retention time and variance using two different methods the commonly used zero dead volume connector and as an alternative the zero length column. Further a technique is presented to estimate extra-column contribution to band broadening for different injection volumes, velocities, and tracers based on representative measurements. When scaling up, often contribution of extra-column volume from laboratory equipment is neglected assuming to be on the safe side, however column efficiency is often lower than efficiency measured for the entire chromatographic system. Relation between system efficiency and column efficiency was investigated using laboratory data and the lumped kinetic model. Depending on the ratio of extra-column volume to retention volume in the system, deduced column efficiency was up to 20% smaller than overall system efficiency. This ratio revealed the misleading nature of the term efficiency loss, when describing influence of extra-column volume on column efficiency. A scheme, which relates the relative variance of the system to the relative extra-column volume, provided an assessment of under- or overestimation of column efficiency. In this article it is shown how scaling up a system based on laboratory data, where extra-column volume contribution is not accounted for, may severely overestimate column efficiency. This overestimation results in underestimated column dimensions at pilot and industrial scale, and hence underperformance of the industrial system.


Subject(s)
Chromatography, Liquid/instrumentation , Chromatography, Liquid/methods , Models, Theoretical , Kinetics
18.
Br J Anaesth ; 117(1): 59-65, 2016 07.
Article in English | MEDLINE | ID: mdl-27154574

ABSTRACT

BACKGROUND: Although deep neuromuscular block (post-tetanic-count 1-2 twitches) improves surgical conditions during laparoscopic retroperitoneal surgery compared with standard block (train-of-four 1-2 twitches), the quality of surgical conditions varies widely, often related to diaphragmatic contractions. Hypocapnia may improve surgical conditions. Therefore we studied the effect of changes in arterial carbon dioxide concentrations on surgical conditions in patients undergoing laparoscopic surgery under general anaesthesia and deep neuromuscular block. METHODS: Forty patients undergoing elective laparoscopic surgery for prostatectomy or nephrectomy received propofol/remifentanil anaesthesia and deep neuromuscular block with rocuronium. Patients were randomized to surgery under hypocapnic or hypercapnic conditions. During surgery, the surgical conditions were evaluated using the 5-point Leiden-Surgical Rating Scale (L-SRS) ranging from 1 (extremely poor conditions) to 5 (optimal conditions) by the surgeon, who was blinded to group. RESULTS: Mean (sd) arterial carbon dioxide concentrations were 4.5 (0.6) [range: 3.8-5.6] kPa under hypocapnic and 6.9 (0.6) [6.1-8.1] kPa under hypercapnic conditions. The L-SRS did not differ between groups: 4.84 (0.4) [4-5] in hypocapnia and 4.77 (0.4) [3.9-5] in hypercapnia. Ninety-nine percent of ratings were good or excellent irrespective of treatment. CONCLUSIONS: Deep neuromuscular block provides good to optimal surgical conditions in laparoscopic retroperitoneal urological surgery, independent of the level of arterial [Formula: see text]. CLINICAL TRIAL REGISTRATION: NCT01968447.


Subject(s)
Anesthesia, General/mortality , Carbon Dioxide/blood , Laparoscopy/methods , Nephrectomy/methods , Neuromuscular Blockade/methods , Prostatectomy/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retroperitoneal Space/surgery , Young Adult
19.
Nutr Metab Cardiovasc Dis ; 26(8): 697-705, 2016 08.
Article in English | MEDLINE | ID: mdl-27052926

ABSTRACT

BACKGROUND AND AIMS: South Asians have an exceptionally high risk of developing cardiovascular disease compared to white Caucasians. A contributing factor might be dysfunction of high density lipoprotein (HDL). We aimed to compare HDL function in different age groups of both ethnicities. METHODS AND RESULTS: HDL functionality with respect to cholesterol efflux, anti-oxidation and anti-inflammation was determined using fasting, apoB-depleted, plasma samples from South Asian and white Caucasian neonates (n = 14 each), adolescent healthy men (n = 12 each, 18-25 y), and adult overweight men (n = 12 each, 40-50 y). Adolescents were subjected to a 5-day high fat high calorie diet (HCD) and adults to an 8-day very low calorie diet (LCD). Additionally, HDL composition was measured in adolescents and adults using (1)H-NMR spectroscopy. Anti-oxidative capacity was lower in South Asian adults before LCD (19.4 ± 2.1 vs. 25.8 ± 1.2%, p = 0.045, 95%-CI = [0.1; 12.7]) and after LCD (16.4 ± 2.4 vs. 27.6 ± 2.7%, p = 0.001, 95%-CI = [4.9; 17.5]). Anti-inflammatory capacity was reduced in South Asian neonates (23.8 ± 1.2 vs. 34.9 ± 1.3%, p = 0.000001, 95%-CI = [-14.6; -7.5]), and was negatively affected by an 8-day LCD only in South Asian adults (-12.2 ± 4.3%, p = 0.005, 95%-CI = [-5.9; -1.2]). Cholesterol efflux capacity was increased in response to HCD in adolescents (South Asians: +6.3 ± 2.9%, p = 0.073, 95%-CI = [-0.02; 0.46], Caucasians: +11.8 ± 3.4%, p = 0.002, 95%-CI = [0.17;0.65]) and decreased after LCD in adults (South Asians: -10.3 ± 2.4%, p < 0.001, 95%-CI = [-0.57; -0.20], Caucasians: -13.7 ± 1.9%, p < 0.00001, 95%-CI = [-0.67; -0.33]). Although subclass analyses of HDL showed no differences between ethnicities, cholesterol efflux correlated best with cholesterol and phospholipid within small HDL compared to other HDL subclasses and constituents. CONCLUSION: Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. CLINICAL TRIAL REGISTRATION: NTR 2473 (URL: http://www.trialregister.nl/).


Subject(s)
Asian People , Caloric Restriction , Cardiovascular Diseases/prevention & control , Cholesterol, HDL/blood , Diet, High-Fat , Obesity/diet therapy , Adolescent , Adult , Age Distribution , Antioxidants/metabolism , Apolipoprotein B-100/blood , Asia/ethnology , Biomarkers/blood , Cardiovascular Diseases/blood , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/ethnology , Diet, High-Fat/adverse effects , Humans , Infant , Inflammation Mediators/blood , Male , Middle Aged , Netherlands/epidemiology , Nuclear Magnetic Resonance, Biomolecular , Obesity/blood , Obesity/diagnosis , Obesity/ethnology , Phospholipids/blood , Risk Assessment , Risk Factors , Time Factors , White People , Young Adult
20.
Neth J Med ; 74(2): 86-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26951354

ABSTRACT

We report on a 39-year-old woman who was intubated because of progressive respiratory failure due to muscle weakness and mucous plugging because of Guillain- Barré syndrome. Shortly after uncomplicated intubation she developed hypotension and a profound tachycardia. The electrocardiogram showed sinus tachycardia with nonspecific ST-T segment changes. Echocardiography showed akinesia of the apex, septum and inferior left ventricular wall with an estimated left ventricular ejection fraction of 10%. It was concluded that the patient was suffering from takotsubo cardiomyopathy. Following treatment, she experienced a complete recovery. Takotsubo cardiomyopathy is a rare complication in Guillain-Barré syndrome; eight other cases have been reported in the literature.


Subject(s)
Guillain-Barre Syndrome/complications , Takotsubo Cardiomyopathy/etiology , Ventricular Function, Left/physiology , Adult , Diagnosis, Differential , Diagnostic Imaging , Echocardiography , Electrocardiography , Female , Guillain-Barre Syndrome/diagnosis , Guillain-Barre Syndrome/physiopathology , Humans , Takotsubo Cardiomyopathy/diagnosis , Takotsubo Cardiomyopathy/physiopathology
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