Experimental and numerical investigation of microdialysis probes for ethanol metabolism studies.

Microdialysis is an important technique for in vivo sampling of tissue's biochemical composition. Understanding the factors that affect the performance of the microdialysis probes and developing methods for sample analysis are crucial for obtaining reliable results. In this work, we used experimental and numerical procedures to study the performance of microdialysis probes having different configurations, membrane materials and dimensions. For alcohol research, it is important to understand the dynamics of ethanol metabolism, particularly in the brain and in other organs, and to simultaneously measure the concentrations of ethanol and its metabolites - acetaldehyde and acetate. Our work provides a comprehensive characterization of three microdialysis probes, in terms of recovery rates and backpressure, allowing for interpretation and optimization of experimental procedures. In vivo experiments were performed to measure the time course concentration of ethanol, acetaldehyde, and acetate in the rat brain dialysate. Additionally, the combination of in vitro experimental results with numerical simulations enabled us to calculate diffusion coefficients of molecules in the microdialysis membranes and study the extent of the depletion effect caused by continuous microdialysis sampling, thus providing additional insights for probe selection and data interpretation.

Infrared spectroscopy for neurochemical monitoring of alcohol and its metabolites.

Continuous measurement of the concentrations of ethanol and its metabolites, acetaldehyde and acetic acid, in vivo is important for the alcohol research community. Most studies only measure ethanol because accurate measurement of all three compounds is challenging. Measurement inside tissue/brain is done using a microdialysis technique, followed by off-line analysis using gas chromatography (GC). To realize simultaneous measurement of ethanol and its metabolites, one can take advantage of infrared (IR) spectroscopy as a rapid and reagent-free method. Here we report a feasibility study of using IR spectroscopy to simultaneously measure ethanol, acetaldehyde and acetic acid in aqueous solution. Different concentrations in transmission mode at different optical pathlengths and using attenuated total reflectance (ATR) were measured. In vitro microdialysis was performed on the mixture of the three compounds, and the collected sample was measured using IR to demonstrate the capability of quantifying the concentrations of the three analytes simultaneously. Lastly, to overcome the limitations of the microdialysis technique, direct measurement using evanescent-field IR spectroscopy can be a potential alternative. A hydrophobic polymer coating that adsorbs ethanol and excludes water, could improve sensitivity. Sorption kinetics in polymethyl methacrylate (PMMA) and polydimethylsiloxane (PDMS) coatings on an ATR crystal were measured. Both polymers demonstrate preferential adsorption of ethanol over water.

Same-Day Discharge Among Patients With Obesity Undergoing Laparoscopic Gynaecologic Oncology Surgery.

OBJECTIVES: To determine the likelihood of same-day discharge (SDD) among patients with obesity undergoing laparoscopic gynaecologic oncology surgery and identify predictors of SDD. METHODS: We conducted a retrospective cohort study of gynaecologic oncology patients who underwent laparoscopic procedures between January 2012 and June 2016. Patients were categorized as non-obese, obese class I/II and obese class III (BMI <30, 30-39.9, and ≥40 kg/m2, respectively). We used univariate and multivariable logistic regression to identify variables associated with SDD. RESULTS: Of 496 patients, 288 were non-obese, 161 were obese class I/II, and 47 were obese class III. Overall, 182 patients (36.7%) were discharged same day; 44% of these were non-obese, 30% class I/II and 15% class III. On multivariable analysis, we found negative predictors for SDD to be obesity (OR 0.54; P = 0.03), procedure length (OR 0.51; P < 0.01), and higher American Society of Anesthesiologists (ASA) score (OR 0.63; P < 0.01), while we found being pre-booked for SDD (OR 9.16; P <0.01) was a positive predictor of SDD. Among all patients with obesity, only procedure length (OR 0.47; P < 0.01) and being pre-booked for SDD (OR 9.67; P < 0.01) were associated with SDD when we controlled for BMI, ASA score, intraoperative complications, type of surgery, and surgical start time. Patients discharged same day were less likely to present to the emergency department within 30 days of surgery (OR 0.48; P = 0.01). CONCLUSION: Among the study cohort and after controlling for potential confounders, women with class I, II, and III obesity had a much lower likelihood of SDD than non-obese women. The only significant predictors of SDD among patients with obesity were duration of procedure and pre-booking for SDD. Further study is needed to identify strategies to improve SDD rates among patients with obesity.

The Feasibility of Laparoscopic Surgery in Gynecologic Oncology for Obese and Morbidly Obese Patients.

BACKGROUND: Surgical interventions are the mainstay of treatment for many gynecological cancers. Although minimally invasive surgery offers many potential advantages, performing laparoscopic pelvic surgery in obese patients remains challenging. To overcome this, many centers have shifted their practice to robotic surgery; however, the high costs associated with robotic surgery are concerning and limit its use. OBJECTIVE: This study aimed to examine the feasibility of performing laparoscopic gynecologic oncology procedures in obese and morbidly obese patients. MATERIALS AND METHODS: This retrospective study evaluated patients who underwent laparoscopic surgeries by a gynecologic oncologist from January 2012 to June 2016 at a designated gynecologic oncology center. Patients were categorized as nonobese (body mass index [BMI] < 30 kg/m), obese (BMI 30-39.9 kg/m), and morbidly obese (BMI ≥ 40 kg/m). Intra and postoperative complications and outcomes were recorded. Group differences were computed with Kruskal-Wallis nonparametric test (continuous) or Fisher exact test (categorical). RESULTS: Of 497 patients, 288 were nonobese (58%), 162 obese (33%), and 47 morbidly obese (9%). Complex surgical procedures were performed in 57.4% of obese patients and 55.3% of morbidly obese patients. Although morbidly obese and obese patients had longer operative times (mean of 181 and 166 minutes vs 144 minutes, P = 0.014), conversion from laparoscopy to laparotomy occurred in 9.05% of all patients, with no group differences. Low intraoperative (9%-11%) and severe postoperative (2.41%) complication rates were observed overall, with no group differences. There was no statistically significant difference in the rate of emergency room visits 30 days postoperation between the 3 BMI groups (P = 0.6108). Average length of postoperative stay was statistically significant (P = 0.0003) but was low overall (1-2 days). Hospital readmission rates were low, with the lowest rate among morbidly obese patients (2.13%). CONCLUSIONS: Our data suggest that laparoscopic gynecologic-oncology procedures for obese patients are feasible and safe.

Early-Onset Convulsive Seizures Induced by Brain Hypoxia-Ischemia in Aging Mice: Effects of Anticonvulsive Treatments.

Aging is associated with an increased risk of seizures/epilepsy. Stroke (ischemic or hemorrhagic) and cardiac arrest related brain injury are two major causative factors for seizure development in this patient population. With either etiology, seizures are a poor prognostic factor. In spite of this, the underlying pathophysiology of seizure development is not well understood. In addition, a standardized treatment regimen with anticonvulsants and outcome assessments following treatment has yet to be established for these post-ischemic seizures. Previous studies have modeled post-ischemic seizures in adult rodents, but similar studies in aging/aged animals, a group that mirrors a higher risk elderly population, remain sparse. Our study therefore aimed to investigate early-onset seizures in aging animals using a hypoxia-ischemia (HI) model. Male C57 black mice 18-20-month-old underwent a unilateral occlusion of the common carotid artery followed by a systemic hypoxic episode (8% O2 for 30 min). Early-onset seizures were detected using combined behavioral and electroencephalographic (EEG) monitoring. Brain injury was assessed histologically at different times post HI. Convulsive seizures were observed in 65% of aging mice post-HI but not in control aging mice following either sham surgery or hypoxia alone. These seizures typically occurred within hours of HI and behaviorally consisted of jumping, fast running, barrel-rolling, and/or falling (loss of the righting reflex) with limb spasms. No evident discharges during any convulsive seizures were seen on cortical-hippocampal EEG recordings. Seizure development was closely associated with acute mortality and severe brain injury on brain histological analysis. Intra-peritoneal injections of lorazepam and fosphenytoin suppressed seizures and improved survival but only when applied prior to seizure onset and not after. These findings together suggest that seizures are a major contributing factor to acute mortality in aging mice following severe brain ischemia and that early anticonvulsive treatment may prevent seizure genesis and improve overall outcomes.

Modeling early-onset post-ischemic seizures in aging mice.

Stroke is the leading cause of seizures and epilepsy in the aged population, with post-stroke seizures being a poor prognostic factor. The pathological processes underlying post-stroke seizures are not well understood and studies of these seizures in aging/aged animals remain scarce. Therefore, our primary objective was to model post-stroke seizures in aging mice (C57 black strain, 16-20 months-old), with a focus on early-onset, convulsive seizures that occur within 24-hours of brain ischemia. We utilized a middle cerebral artery occlusion model and examined seizure activity and brain injury using combined behavioral and electroencephalographic monitoring and histological assessments. Aging mice exhibited vigorous convulsive seizures within hours of the middle cerebral artery occlusion. These seizures manifested with jumping, rapid running, barrel-rolling and/or falling all in the absence of hippocampal-cortical electrographic discharges. Seizure development was closely associated with severe brain injury and acute mortality. Anticonvulsive treatments after seizure occurrence offered temporary seizure control but failed to improve animal survival. A separate cohort of adult mice (6-8 months-old) exhibited analogous early-onset convulsive seizures following the middle cerebral artery occlusion but had better survival outcomes following anticonvulsive treatment. Collectively, our data suggest that early-onset convulsive seizures are a result of severe brain ischemia in aging animals.

Effects of neonatal hypoxic-ischemic episodes on late seizure outcomes in C57 black mice.

We examined brain injury and seizures in adult C57 black mice (C57/BL6) that underwent neonatal hypoxic-ischemic (HI) episodes. Mouse pups of 7 days-old underwent a ligation of the right common carotid artery and a subsequent hypoxic challenge (8% O2 for 45min). Post-HI mice were implanted with intracranial electrodes at 2-3 months of age, subjected to behavioral/EEG recordings and hippocampal electrical stimulation in next several months and then euthanized for brain histological assessments at ages of 11-12 months. Histological assessment revealed ipsilateral brain infarctions in 9 post-HI animals. Evident motor seizures were found to occur in only 2 animals with histologically identified cystic infarctions but not in the 21 post-HI animals with or without infarctions. In response to the hippocampal stimulation, post-HI animals were less prone than sham controls to evoked motor seizures. We thus suggest that adult C57 black mice may have low propensity of developing epileptic seizures following the neonatal HI episode. Our present observations may be relevant to future investigation of post-HI epileptogenesis in mouse models.