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An automated analytical method for the determination of felbamate in human plasma by robotic sample preparation and reversed-phase high performance liquid chromatography.

An automated analytical method for the determination of felbamate in human plasma is described. Sample cleanup and preparation was performed by means of a Zymate II laboratory robot and consisted of a liquid-liquid extraction of felbamate and the internal standard, primidone, from human plasma to dichloromethane. The dichloromethane was evaporated and reconstituted in a phosphate buffer. Separation was performed by reversed-phase high performance liquid chromatography using a 5 microns Hypersil ODS column (150 x 4.6 mm) and a mobile phase consisting of a mixture of phosphate buffer (pH = 6.5, 0.015 M) and acetonitrile (79:21, v/v). Quantitation was performed by measurement of the UV absorbance at a wavelength of 210 nm. The lower limit of quantitation was 0.100 micrograms ml-1 using 200 microliters of plasma. The mean absolute analytical recovery of felbamate was 75.2% (n = 28). The recovery of the internal standard, primidone was 74.7% (n = 10). The within-day precision was below 3.8% at all concentration levels, except at the lower limit of quantitation (18.3%). The within-day accuracy varied between -3.7 and +7.4%. The between-day precision was below 5.0% at all concentration levels. The between-day accuracy of the method varied between -5.7 and +1.6%. The selectivity of the method towards several other anti-epileptic drugs has been demonstrated.

Anticonvulsants↗

A robotics-based liquid chromatographic assay for the measurement of atovaquone in plasma.

A precise and specific robotics-based liquid chromatographic (LC) method for measuring atovaquone concentrations in plasma was developed and validated, and the method was compared with an existing manual LC method. The compound was isolated from plasma by liquid-liquid extraction, separated by reversed-phase LC, and quantitated against an internal standard with UV detection. Least-squares linear regression with 1/concentration2 weighting was used as the calibration model. The range of the calibration curve for the assay under routine conditions was 0.25-50 micrograms ml-1. No endogenous interferences with the compound or the internal standard were noted in either untreated human plasma or in plasma from patients enrolled in Phase III clinical trials of atovaquone. The accuracy of the assay (determined as the percent bias) ranged from -4.8% to -9.4% in the validation runs. The intra- and interassay precisions (determined as the relative standard deviation) were less than 6.8% and 6.4%, respectively. The contribution of an internal standard on assay accuracy and precision also was examined. Interassay variability was marginally improved by the incorporation of an internal standard to the assay; accuracy and intra-assay precision were essentially unchanged. A paired t-test between estimates of atovaquone concentrations in healthy volunteer and HIV + patient human plasma samples assayed by the automated and manual methods demonstrated no significant difference (p = 0.31) between the values determined by each method.

Antifungal Agents↗

Mechanical strain on the human skull in a humanoid robotic model.

Patterns of strain were analyzed in a dry human skull at 15 different regions on the lateral and medial surfaces of the mandible. The strains were induced with a human robotic system that represented each of 8 bilateral muscles by a DC servomotor connected to a wire and pulley. The tractions of the simulated muscles (masseter, medial pterygoid, anterior temporalis, and posterior temporalis) were increased from 1x to 4x with each representing different levels of traction or force (5, 3, 4, and 4 N, respectively). The study was done with the teeth in maximum intercuspal occlusion. Bite forces were also measured with a transducer and reached a maximum of 40 N on the posterior teeth with less force on the anterior dentition. The smallest traction level (1x) developed some small strains. At 2x, compressive strains developed more on the medial (lingual) side beneath the molars through the corpus and radiated into the anterior ramus. Strains at 3x to 4x significantly increased both the tensile and compressive strains throughout the mandible with more strains developing in the ramus. The increased bilateral traction and loading developed significant compressive forces on both sides of the mandible. Evaluation of disparities between compressive and tensile strains at one site, and comparison between the medial and lateral sides of strain, suggested some visible distortion of portions of the mandible under the higher loads.

Analysis of Variance↗

Robotic mammary takedown and off-pump bypass surgery for single-vessel disease of the left anterior descending coronary artery.

Robotic takedown of the left internal mammary artery and direct off-pump anastomosis to the left anterior descending artery through small thoracotomy incisions can be done safely with minimal morbidity and is associated with decreased blood loss, decreased ventilatory requirements, less intensive care unit stay, and less overall length of stay. It should be considered as an alternative to percutaneous angioplasty and stenting for those with isolated left anterior descending artery disease.

Adult↗

Robotic arrhythmia surgery and resynchronization.

Over the last decade, significant technological advancements have occurred in cardiac surgery. One such breakthrough has been the use of robotic telemanipulation systems, which allow the surgeon to perform cardiac surgery through a minimally invasive approach. As a result, surgery for atrial fibrillation and resynchronization therapy for congestive heart failure have been increasingly incorporated into the surgeon's armamentarium.

Arrhythmias, Cardiac↗

Building a surgical robotics program.

Building a strong institutional robotics program requires commitment from administrative and clinical departments. Here we present issues to be considered when developing such a program, including development of a pathway for introduction of the technology into patient care, team recruitment, creation of an objective-based curriculum, multispecialty training, and proper patient selection.

Curriculum↗

Function of the anterior cruciate ligament after unicompartmental knee arthroplasty: an in vitro robotic study.

The objective of this study was to investigate the role of the anterior cruciate ligament (ACL) in the anterior-posterior (AP) stability of the knee after unicompartmental knee arthroplasty (UKA). AP tibial loads were applied to human cadaveric knee specimens using a robotic testing system. After UKA, the knee exhibited tibial translations similar to that of the native knee, and the forces in the ACL were also similar to those seen in the native knee. The ACL-deficient knee after UKA exhibited significantly greater anterior tibial translations than the native knee and the knee after UKA with an intact ACL. These data suggest that medial UKA does not alter the anterior stability of the knee, but a functional ACL is necessary to ensure normal stability after UKA.

Aged↗

First robotic endoscopic epicardial isolation of the pulmonary veins with microwave energy in a patient in chronic atrial fibrillation.

The pulmonary veins have been demonstrated to play an important role in generating atrial fibrillation. We report the first successful endoscopic epicardial isolation of the pulmonary veins in a patient with permanent atrial fibrillation, along with a 1-year follow-up. The procedure consisted of making a conduction block around the pulmonary veins with a flexible microwave energy delivery probe. The probe was placed endoscopically on the left atrial epicardium with the aid of robotic instruments.

Adrenergic beta-Antagonists↗

Trajectory of coronary motion and its significance in robotic motion cancellation.

OBJECTIVES: To characterize remaining coronary artery motion of beating pig hearts after stabilization with an 'Octopus' using an optical remote analysis technique. METHODS: Three pigs (40, 60 and 65 kg) underwent full sternotomy after receiving general anesthesia. An 8-bit high speed black and white video camera (50 frames/s) coupled with a laser sensor (60 microm resolution) were used to capture heart wall motion in all three dimensions. Dopamine infusion was used to deliberately modulate cardiac contractility. Synchronized ECG, blood pressure, airway pressure and video data of the region around the first branching point of the left anterior descending (LAD) coronary artery after Octopus stabilization were captured for stretches of 8 s each. Several sequences of the same region were captured over a period of several minutes. Computerized off-line analysis allowed us to perform minute characterization of the heart wall motion. RESULTS: The movement of the points of interest on the LAD ranged from 0.22 to 0.81 mm in the lateral plane (x/y-axis) and 0.5-2.6 mm out of the plane (z-axis). Fast excursions (>50 microm/s in the lateral plane) occurred corresponding to the QRS complex and the T wave; while slow excursion phases (<50 microm/s in the lateral plane) were observed during the P wave and the ST segment. The trajectories of the points of interest during consecutive cardiac cycles as well as during cardiac cycles minutes apart remained comparable (the differences were negligible), provided the hemodynamics remained stable. Inotrope-induced changes in cardiac contractility influenced not only the maximum excursion, but also the shape of the trajectory. Normal positive pressure ventilation displacing the heart in the thoracic cage was evident by the displacement of the reference point of the trajectory. CONCLUSIONS: The movement of the coronary artery after stabilization appears to be still significant. Minute characterization of the trajectory of motion could provide the substrate for achieving motion cancellation for existing robotic systems. Velocity plots could also help improve gated cardiac imaging.

Animals↗

Robotic radical prostatectomy with the "Veil of Aphrodite" technique: histologic evidence of enhanced nerve sparing.

OBJECTIVE: We have recently described a modification (Veil of Aphrodite) designed to preserve the lateral prostatic fascia (LPF) during robotic prostatectomy. Here, we histologically compare the Veil of Aphrodite technique (VT) and standard nerve-sparing technique (ST). METHODS: Thirty-six consecutive prostatectomies performed by a single surgeon were processed by the whole-mount method. The right and left anterolateral (AL) zones of each prostate were independently evaluated for LPF, plane of excision, capsular incision/margin status, margin clearance, and quantitative analysis of periprostatic nerve bundles using S100 immunostain. RESULTS: There were 42 AL zones with ST and 30 with VT. In all 42 ST zones, the plane of excision was outside the prostate and a rim of LPF was present. The mean margin clearance was 1.4 mm (0.6-2.8 mm) and the mean nerve bundle count was 10 (3-19). Capsular incision and margin status were negative in all 42. For VT, 24 of 30 zones lacked LPF and the plane of excision ran just by the prostatic edge. The mean margin clearance was 0.3 mm (0-1.7 mm) and the mean nerve bundle count was two (0-11). Two VT AL zones revealed capsular incision; the margin was negative for tumour in all 30. Differences in the margin clearances and nerve bundle counts between ST and VT were statistically significant (p < 0.0001). CONCLUSIONS: The LPF contains nerve bundles that run along the surface of the AL zones. The VT is a safe procedure that effectively preserves the LPF and appears to provide enhanced nerve sparing as compared to the ST.

Aged↗

Robotic-assisted Heller myotomy versus laparoscopic Heller myotomy for the treatment of esophageal achalasia: multicenter study.

Laparoscopic Heller myotomy (LHM) has become the standard treatment option for achalasia. The incidence of esophageal perforation reported is about 5%-10%. Robotically assisted Heller myotomy (RAHM) is emerging as a safe alternative to LHM. Data comparing the two approaches are scant. The aim of this study was to compare RAHM with LHM in terms of efficacy and safety for treatment of achalasia. A total of 121 patients underwent surgical treatment of achalasia at three institutions. A retrospective review of prospectively collected perioperative data was performed. Patients were divided into two groups: group A (RAHM), 59 patients, and group B (LHM), 62 patients. All the operations were completed using minimally invasive techniques. There were 63 women and 58 men, with a mean age of 45 +/- 19 years (14-82 years). Fifty-one percent of patients in group A and 95% of patients in group B reported weight loss. Duration of symptoms was equal for both groups. Dysphagia was the main complaint in both groups (P = NS). There was no difference in preoperative endoscopic treatment in both groups (44% versus 27%, P = NS). Operative time was significantly shorter for LHM in the first half of the experience (141 +/- 49 versus 122 +/- 44 minutes, P < .05). However, in the last 30 cases there was no difference in operative time between the groups (P = NS). Intraoperative complications (esophageal perforation) were more frequent in group B (16% versus 0%). The incidence of postoperative heartburn did not differ by group. There were no deaths. At 18 and 22 months, 92% and 90% of patients had relief of their dysphagia. This study suggests that RAHM is safer than LHM, because it decreases the incidence of esophageal perforation to 0%, even in patients who had previous treatment. At short-term follow-up, relief of dysphagia was equally achieved in both groups

Adult↗

Legal and ethical issues in telemedicine and robotics.

Modern medical concerns with telemedicine and robotics practiced across national or other jurisdictional boundaries engage the historical, complex area of law called conflict of laws. An initial concern is whether a practitioner licensed only in jurisdiction A who treats a patient in jurisdiction B violates B's laws. Further concerns are whether a practitioner in A who violates a contract or treats a patient in B negligently incurs liability in B, A, or both, and, if treatment lawful in A is unlawful in B, whether the practitioner commits a crime. Judicial procedures are set by courts in which proceedings are initiated, but courts may decline jurisdiction due to inconvenience to parties. If courts accept jurisdiction, they may apply their own substantive legal rules, but may find that the rules of a conflicting jurisdiction should apply. Cross-border care should not change usual medical ethics, for instance on confidentiality, but may mitigate or aggravate migration of specialists.

Ethics, Clinical↗

A neural network model for reconstructing EMG signals from eight shoulder muscles: consequences for rehabilitation robotics and biofeedback.

This paper demonstrates the ability of a fully connected feed forward neural network (FFNN) using the backpropagation training algorithm to predict the electromyography (EMG) signal from eight muscles of the shoulder for both exercises not used for training and EMG signals from subjects not used for training. The network showed a good predictive ability for subjects not used for training (r(2) between 0.33 and 0.84) and for activities not used for training (r(2) between 0.56 and 0.89). This may have applications for patients, physical therapists and doctors to monitor patient performance by reviewing the level of agreement between the patient EMG and the predicted EMG. Coupled with traditional methods of evaluation, EMG can provide an excellent measure of how well a patient has responded or is responding to treatment. Incorporating robotic technology could facilitate the use of EMG as an input to an intelligent decision making algorithm used to increase or decrease the level of difficulty according to patient performance.

Adult↗

Rapid, automated screening method for enzymatic transformations using a robotic system and supercritical fluid chromatography.

An automated screening method was developed for enzymatic transformations using a robotic system and rapid chiral supercritical fluid chromatography (SFC) analysis with a run time of 1.5 min. The method accelerates the enzyme selection process for screening biocatalysts, where a large number of enzymes are evaluated for activity and enantioselectivity. Kinetic resolution of secondary alcohols by enzymatic transesterification was used as a prototype for method development. The rapid automated method can be used effectively for screening enzymes and optimizing reaction conditions in biocatalysis.

Automation↗

Combined transurethral and laparoscopic partial cystectomy and robot-assisted bladder repair for the treatment of bladder endometrioma.

A 40-year-old nulliparous woman with a 7-year history of progressive abdominal discomfort and lower urinary tract symptoms was diagnosed with a deeply infiltrating 4-cm bladder endometrioma. After failing conservative therapy, she was treated with simultaneous transurethral and laparoscopic partial cystectomy and robot-assisted bladder reconstruction. She remained symptom free at last follow-up.

Adult↗

W. Grey Walter, pioneer in the electroencephalogram, robotics, cybernetics, artificial intelligence.

With the announcement by William Lennox at the 1935 London International Neurology Congress of the use of electroencephalography in the study of epilepsy, it became evident that a new and powerful technique for the investigation of seizures had been discovered. William Grey Walter, a young researcher finishing his post-graduate studies at Cambridge, was selected to construct and study the EEG in clinical neurology at the Maudsley Hospital, London. His hugely productive pioneering career in the use of EEG would eventually lead to groundbreaking work in other fields --the emerging sciences of robotics, cybernetics, and early work in artificial intelligence. In this historical note his pioneering work in the fields of clinical neurophysiology is documented, both in the areas of epileptology and tumour detection. His landmark contributions to clinical neurophysiology are worthy of documentation.

Artificial Intelligence↗

Automated robotic liquid handling/laser-based nephelometry system for high throughput measurement of kinetic aqueous solubility.

The ability to rapidly and consistently measure aqueous solubility in a preclinical environment is critical to the successful identification of promising discovery compounds. The advantage of an early solubility screen is timely attrition of compounds likely to fail due to poor absorption or low bioavailability before more costly screens are performed. However, due to the large number of compounds and limited sample amounts, thermodynamic solubility measurements are not feasible at this stage. A kinetic solubility measurement is an alternative to thermodynamic measurements at the discovery stage that provides a rank listing of solubility values with minimal sample requirements. A kinetic solubility measurement is attractive from an automation vantage because it features rapid data acquisition and is amenable to multi-well formats. We describe the use of a robotic liquid/plate handler coupled to nephelometry detection for the measurement of kinetic solubility. We highlight the liquid handling validation, serial dilution parameters, and a comparison to the previous method. Experiments to further enhance throughput, or increase confidence in the automation steps, are described and the effects of these experiments are presented. In our integrated nephelometry method, we observe rapid liquid handling with an error of less than 10%, after a series of validation studies, and a sample throughput up to 1800 compounds per week. We compare the nephelometry method with our semi-thermodynamic flow-injection analysis (FIA) method, and find a 75% bin agreement between the methods.

Kinetics↗