Separator fluid volume requirements in multi-infusion settings

INTRODUCTION. Intravenous (IV) therapy is a widely used method for the administration of medication in hospitals worldwide. ICU and surgical patients in particular often require multiple IV catheters due to incompatibility of certain drugs and the high complexity of medical therapy. This increases discomfort by painful invasive procedures, the risk of infections and costs of medication and disposable considerably. When different drugs are administered through the same lumen, it is common ICU practice to flush with a neutral fluid between the administration of two incompatible drugs in order to optimally use infusion lumens. An important constraint for delivering multiple incompatible drugs is the volume of separator fluid that is sufficient to safely separate them. OBJECTIVES. In this pilot study we investigated whether the choice of separator fluid, solvent, or administration rate affects the separator volume required in a typical ICU infusion setting. METHODS. A standard ICU IV line (2m, 2ml, 1mm internal diameter) was filled with methylene blue (40 mg/l) solution and flushed using an infusion pump with separator fluid. Independent variables were solvent for methylene blue (NaCl 0.9% vs. glucose 5%), separator fluid (NaCl 0.9% vs. glucose 5%), and administration rate (50, 100, or 200 ml/h). Samples were collected using a fraction collector until <2% of the original drug concentration remained and were analyzed using spectrophotometry. RESULTS. We did not find a significant effect of administration rate on separator fluid volume. However, NaCl/G5% (solvent/separator fluid) required significantly less separator fluid than NaCl/NaCl (3.6 ± 0.1 ml vs. 3.9 ± 0.1 ml, p <0.05). Also, G5%/G5% required significantly less separator fluid than NaCl/NaCl (3.6 ± 0.1 ml vs. 3.9 ± 0.1 ml, p <0.05). The significant decrease in required flushing volume might be due to differences in the viscosity of the solutions. However, mean differences were small and were most likely caused by human interactions with the fluid collection setup. The average required flushing volume is 3.7 ml. CONCLUSIONS. The choice of separator fluid, solvent or administration rate had no impact on the required flushing volume in the experiment. Future research should take IV line length, diameter, volume and also drug solution volumes into account in order to provide a full account of variables affecting the required separator fluid volume

Aneurysm of the Superior Posterior Pancreatic-Duodenal Artery Presenting with Recurrent Syncopes

We present a 61-year-old woman with hypovolemic shock due to a ruptured aneurysm of the superior posterior pancreatic-duodenal artery in whom recurrent syncopes were the first presenting sign of pancreatic-duodenal artery aneurysm (PDAA). PDAA is a rare but life-threatening condition. The widely varying symptomatology may lead to a delay in diagnosis and treatment. Patients with atypical symptoms, such as vague abdominal pain, recurrent dizziness or syncope, may actually suffer from a sentinel bleeding of the vascular malformation. Radiological imaging, especially selective angiography, may provide a diagnostic as well as a therapeutic tool in these patients

Effects of force load, muscle fatigue and extremely low frequency magnetic stimulation on EEG signals during side arm lateral raise task

Objective: This study was to quantitatively investigate the effects of force load, muscle fatigue and extremely low frequency (ELF) magnetic stimulation on electroencephalography (EEG) signal features during side arm lateral raise task. Approach: EEG signals were recorded by a BIOSEMI Active Two system with Pin-Type active-electrodes from 18 healthy subjects when they performed the right arm side lateral raise task (90° away from the body) with three different loads (0 kg, 1 kg and 3 kg; their order was randomized among the subjects) on the forearm. The arm maintained the loads until the subject felt exhausted. The first 10 s recording for each load was regarded as non-fatigue status and the last 10 s before the subject was exhausted as fatigue status. The subject was then given a 5 min resting between different loads. Two days later, the same experiment was performed on each subject except that ELF magnetic stimulation was applied to the subject's deltoid muscle during the 5 min resting period. EEG features from C3 and C4 electrodes including the power of alpha, beta and gamma and sample entropy were analyzed and compared between different loads, non-fatigue/fatigue status, and with/without ELF magnetic stimulation. Main results: The key results were associated with the change of the power of alpha band. From both C3-EEG and C4-EEG, with 1 kg and 3 kg force loads, the power of alpha band was significantly smaller than that from 0 kg for both non-fatigue and fatigue periods (all p    0.05 for all the force loads except C4-EEG with ELF simulation). The power of alpha band at fatigue status was significantly increased for both C3-EEG and C4-EEG when compared with the non-fatigue status (p    0.05, except between non-fatigue and fatigue with magnetic stimulation in gamma band of C3-EEG at 1 kg, and in the SampEn at 1 kg and 3 kg force loads from C4-EEG). Significance: Our study comprehensively quantified the effects of force, fatigue and the ELF magnetic stimulation on EEG features with difference forces, fatigue status and ELF magnetic stimulation

Activity and Process Stability of Purified Green Pepper (Capsicum annuum) Pectin Methylesterase

Pectin methylesterase (PME) from green bell peppers (Capsicum annuum) was extracted and purified by affinity chromatography on a CNBr-Sepharose-PMEI column. A single protein peak with pectin methylesterase activity was observed. For the pepper PME, a biochemical characterization in terms of molar mass (MM), isoelectric points (pI), and kinetic parameters for activity and thermostability was performed. The optimum pH for PME activity at 22 °C was 7.5, and its optimum temperature at neutral pH was between 52.5 and 55.0 °C. The purified pepper PME required the presence of 0.13 M NaCl for optimum activity. Isothermal inactivation of purified pepper PME in 20 mM Tris buffer (pH 7.5) could be described by a fractional conversion model for lower temperatures (55?57 °C) and a biphasic model for higher temperatures (58?70 °C). The enzyme showed a stable behavior toward high-pressure/temperature treatments. Keywords: Capsicum annuum; pepper; pectin methylesterase; purification; characterization; thermal and high-pressure stabilit

Interplay of brain structure and function in neonatal congenital heart disease

Objective: To evaluate whether structural and microstructural brain abnormalities in neonates with congenital heart disease (CHD) correlate with neuronal network dysfunction measured by analysis of EEG connectivity. Methods: We studied a prospective cohort of 20 neonates with CHD who underwent continuous EEG monitoring before surgery to assess functional brain maturation and network connectivity, structural magnetic resonance imaging (MRI) to determine the presence of brain injury and structural brain development, and diffusion tensor MRI to assess brain microstructural development. Results: Neonates with MRI brain injury and delayed structural and microstructural brain development demonstrated significantly stronger high-frequency (beta and gamma frequency band) connectivity. Furthermore, neonates with delayed microstructural brain development demonstrated significantly weaker low-frequency (delta, theta, alpha frequency band) connectivity. Neonates with brain injury also displayed delayed functional maturation of EEG background activity, characterized by greater background discontinuity. Interpretation: These data provide new evidence that early structural and microstructural developmental brain abnormalities can have immediate functional consequences that manifest as characteristic alterations of neuronal network connectivity. Such early perturbations of developing neuronal networks, if sustained, may be responsible for the persistent neurocognitive impairment prevalent in adolescent survivors of CHD. These foundational insights into the complex interplay between evolving brain structure and function may have relevance for a wide spectrum of neurological disorders manifesting early developmental brain injury

Increasing metformin concentrations and its excretion in both rat and porcine ex vivo normothermic kidney perfusion model

INTRODUCTION: Metformin can accumulate and cause lactic acidosis in patients with renal insufficiency. Metformin is known to inhibit mitochondria, while renal secretion of the drug by proximal tubules indirectly requires energy. We investigated whether addition of metformin before or during ex vivo isolated normothermic machine perfusion (NMP) of porcine and rat kidneys affects its elimination.RESEARCH DESIGN AND METHODS: First, Lewis rats were pretreated with metformin or saline the day before nephrectomy. Subsequently, NMP of the kidney was performed for 90 min. Metformin was added to the perfusion fluid in one of three different concentrations (none, 30 mg/L or 300 mg/L). Second, metformin was added in increasing doses to the perfusion fluid during 4 hours of NMP of porcine kidneys. Metformin concentration was determined in the perfusion fluid and urine by liquid chromatography-tandem mass spectrometry.RESULTS: Metformin clearance was approximately 4-5 times higher than creatinine clearance in both models, underscoring secretion of the drug. Metformin clearance at the end of NMP in rat kidneys perfused with 30 mg/L was lower than in metformin pretreated rats without the addition of metformin during perfusion (both p≤0.05), but kidneys perfused with 300 mg/L trended toward lower metformin clearance (p=0.06). Creatinine clearance was not different between treatment groups. During NMP of porcine kidneys, metformin clearance peaked at 90 min of NMP (18.2±13.7 mL/min/100 g). Thereafter, metformin clearance declined, while creatinine clearance remained stable. This observation can be explained by saturation of metformin transporters with a Michaelis-Menten constant (95% CI) of 23.0 (10.0 to 52.3) mg/L.CONCLUSIONS: Metformin was secreted during NMP of both rat and porcine kidneys. Excretion of metformin decreased under increasing concentrations of metformin, which might be explained by saturation of metformin transporters rather than a self-inhibitory effect. It remains unknown whether a self-inhibitory effect contributes to metformin accumulation in humans with longer exposure times.</p

Brain Vital Signs: Expanding From the Auditory to Visual Modality

The critical need for rapid objective, physiological evaluation of brain function at point-of-care has led to the emergence of brain vital signs—a framework encompassing a portable electroencephalography (EEG) and an automated, quick test protocol. This framework enables access to well-established event-related potential (ERP) markers, which are specific to sensory, attention, and cognitive functions in both healthy and patient populations. However, all our applications to-date have used auditory stimulation, which have highlighted application challenges in persons with hearing impairments (e.g., aging, seniors, dementia). Consequently, it has become important to translate brain vital signs into a visual sensory modality. Therefore, the objectives of this study were to: 1) demonstrate the feasibility of visual brain vital signs; and 2) compare and normalize results from visual and auditory brain vital signs. Data were collected from 34 healthy adults (33 ± 13 years) using a 64-channel EEG system. Visual and auditory sequences were kept as comparable as possible to elicit the N100, P300, and N400 responses. Visual brain vital signs were elicited successfully for all three responses across the group (N100:&nbsp;F&nbsp;= 29.8380,&nbsp;p&nbsp;&lt; 0.001; P300:&nbsp;F&nbsp;= 138.8442,&nbsp;p&nbsp;&lt; 0.0001; N400:&nbsp;F&nbsp;= 6.8476,&nbsp;p&nbsp;= 0.01). Initial auditory-visual comparisons across the three components showed attention processing (P300) was found to be the most transferrable across modalities, with no group-level differences and correlated peak amplitudes (rho = 0.7,&nbsp;p&nbsp;= 0.0001) across individuals. Auditory P300 latencies were shorter than visual (p&nbsp;&lt; 0.0001) but normalization and correlation (r&nbsp;= 0.5,&nbsp;p&nbsp;= 0.0033) implied a potential systematic difference across modalities. Reduced auditory N400 amplitudes compared to visual (p&nbsp;= 0.0061) paired with normalization and correlation across individuals (r&nbsp;= 0.6,&nbsp;p&nbsp;= 0.0012), also revealed potential systematic modality differences between reading and listening language comprehension. This study provides an initial understanding of the relationship between the visual and auditory sequences, while importantly establishing a visual sequence within the brain vital signs framework. With both auditory and visual stimulation capabilities available, it is possible to broaden applications across the lifespan. The critical need for rapid objective, physiological evaluation of brain function at point-of-care has led to the emergence of brain vital signs—a framework encompassing a portable electroencephalography (EEG) and an automated, quick test protocol. This framework enables access to well-established event-related potential (ERP) markers, which are specific to sensory, attention, and cognitive functions in both healthy and patient populations. However, all our applications to-date have used auditory stimulation, which have highlighted application challenges in persons with hearing impairments (e.g., aging, seniors, dementia). Consequently, it has become important to translate brain vital signs into a visual sensory modality. Therefore, the objectives of this study were to: 1) demonstrate the feasibility of visual brain vital signs; and 2) compare and normalize results from visual and auditory brain vital signs. Data were collected from 34 healthy adults (33 ± 13 years) using a 64-channel EEG system. Visual and auditory sequences were kept as comparable as possible to elicit the N100, P300, and N400 responses. Visual brain vital signs were elicited successfully for all three responses across the group (N100:&nbsp;F&nbsp;= 29.8380,&nbsp;p&nbsp;&lt; 0.001; P300:&nbsp;F&nbsp;= 138.8442,&nbsp;p&nbsp;&lt; 0.0001; N400:&nbsp;F&nbsp;= 6.8476,&nbsp;p&nbsp;= 0.01). Initial auditory-visual comparisons across the three components showed attention processing (P300) was found to be the most transferrable across modalities, with no group-level differences and correlated peak amplitudes (rho = 0.7,&nbsp;p&nbsp;= 0.0001) across individuals. Auditory P300 latencies were shorter than visual (p&nbsp;&lt; 0.0001) but normalization and correlation (r&nbsp;= 0.5,&nbsp;p&nbsp;= 0.0033) implied a potential systematic difference across modalities. Reduced auditory N400 amplitudes compared to visual (p&nbsp;= 0.0061) paired with normalization and correlation across individuals (r&nbsp;= 0.6,&nbsp;p&nbsp;= 0.0012), also revealed potential systematic modality differences between reading and listening language comprehension. This study provides an initial understanding of the relationship between the visual and auditory sequences, while importantly establishing a visual sequence within the brain vital signs framework. With both auditory and visual stimulation capabilities available, it is possible to broaden applications across the lifespan

CD4(+) T-cell responses mediate progressive neurodegeneration in experimental ischemic retinopathy

Retinal ischemic events, which result from occlusion of the ocular vasculature share similar causes as those for central nervous system stroke and are among the most common cause of acute and irreversible vision loss in elderly patients. Currently, there is no established treatment, and the condition often leaves patients with seriously impaired vision or blindness. The immune system, particularly T-cell- mediated responses, is thought to be intricately involved, but the exact roles remain elusive. We found that acute ischemia-reperfusion injury to the retina induced a prolonged phase of retinal ganglion cell loss that continued to progress during 8 weeks after the procedure. This phase was accompanied by microglial activation and CD4+ T-cell infiltration into the retina. Adoptive transfer of CD4+ T cells isolated from diseased mice exacerbated retinal ganglion cell loss in mice with retinal reperfusion damage. On the other hand, T-cell deficiency or administration of T-cell or interferon-gamma-neutralizing antibody attenuated retinal ganglion cell degeneration and retinal function loss after injury. These findings demonstrate a crucial role for T-cell-mediated responses in the pathogenesis of neural ischemia. These findings point to novel therapeutic targets of limiting or preventing neuron and function loss for currently untreatable conditions of optic neuropathy and/or central nervous system ischemic stroke.Ophthalmic researc