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Biomedical subjects

M Seger

Publications and source records attributed to M Seger.

At least 19 recordsLinked to original sources

AAM-based segmentation for imaging cardiac electrophysiology.

OBJECTIVES: Activation time (AT) imaging from electrocardiographic (ECG) mapping data has been developing for several years. By coupling 4-dimensional volume data (3D + time) the electrical sequence can be computed non-invasively. In this paper an approach for extracting the ventricular and atrial blood masses for structurally normal hearts by using cine-gated short-axis data obtained via magnetic resonance imaging (MRI) is introduced. METHODS: The blood masses are extracted by employing Active Appearance Models (AAMs). The ventricular blood masses are segmented, applying the AAMs after providing apex cordis and base of the heart in the volume data, whereas the more complex geometry of the atria requires a more specific attempt. On account of this the atrium was divided into three divisions of appearance, where the images of the volume data in the related divisions have a maximum affinity. The first division reaches from the base of the heart to initial visibility of the upper and left lower pulmonary vein. The second division up from there to the last occurrence and the third division from there to the end of the visibility of the right upper and lower pulmonary vein. After extracting the cardiac blood masses the result gets triangulated and remeshed for activation time imaging. RESULTS: With this method the cardiac models of eight patients were extracted and the AT imaging approach was applied to single-beat ECG data of atrial and ventricular depolarization. CONCLUSION: The advantage of the proposed AAM approach is that only a few initial parameters have to be set. Therefore, the approach can be integrated into a processing pipeline that works semi-automatically. The extracted models can be used for further investigations.

Atrial Function↗

Atrial and ventricular myocardium extraction using model-based techniques.

OBJECTIVES: This paper presents an efficient approach for extracting myocardial structures from given atrial and ventricular blood masses to enable non-invasive estimation of electrical excitation in human atria and ventricles. METHODS: Based on given segmented atrial and ventricular blood masses, the approach constructs the myocardial structure directly, in the case that the myocardium can be detected in the volume data, or by using mean model information, in the case that the myocardium cannot be seen in the volume data due to image modalities or artefacts. The approach employs mathematical and gray-value morphology operations. Regulated by the spatial visibility of the myocardial structure in the medical image data especially the atrial myocardium needs to be estimated repeatedly using the a-priori knowledge given by the anatomy. RESULTS: The approach was tested using eight patient data sets. The reconstruction process yielded satisfying results with respect to an efficient generation of a volume conductor model which is essential when trying to implement the estimation of electrical excitation in clinical application. CONCLUSION: The approach yields ventricular and atrial models that qualify for cardiac source imaging in a clinical setting.

Algorithms↗

Lead field computation for the electrocardiographic inverse problem--finite elements versus boundary elements.

In order to be able to solve the inverse problem of electrocardiography, the lead field matrix (transfer matrix) has to be calculated. The two methods applied for computing this matrix, which are compared in this study, are the boundary element method (BEM) and the finite element method (FEM). The performance of both methods using a spherical model was investigated. For a comparable discretization level, the BEM yields smaller relative errors compared to analytical solutions. The BEM needs less computation time, but a larger amount of memory. Inversely calculated myocardial activation times using either the FEM or BEM computed lead field matrices give similar activation time patterns. The FEM, however, is also capable of considering anisotropic conductivities. This property might have an impact for future development, when also individual myocardial fiber architecture can be considered in the inverse formulation.

Anisotropy↗

A signal processing pipeline for noninvasive imaging of ventricular preexcitation.

OBJECTIVES: Noninvasive imaging of the cardiac activation sequence in humans could guide interventional curative treatment of cardiac arrhythmias by catheter ablation. Highly automated signal processing tools are desirable for clinical acceptance. The developed signal processing pipeline reduces user interactions to a minimum, which eases the operation by the staff in the catheter laboratory and increases the reproducibility of the results. METHODS: A previously described R-peak detector was modified for automatic detection of all possible targets (beats) using the information of all leads in the ECG map. A direct method was applied for signal classification. The algorithm was tuned for distinguishing beats with an adenosine induced AV-nodal block from baseline morphology in Wolff-Parkinson-White (WPW) patients. Furthermore, an automatic identification of the QRS-interval borders was implemented. RESULTS: The software was tested with data from eight patients having overt ventricular preexcitation. The R-peak detector captured all QRS-complexes with no false positive detection. The automatic classification was verified by demonstrating adenosine-induced prolongation of ventricular activation with statistical significance (p <0.001) in all patients. This also demonstrates the performance of the automatic detection of QRS-interval borders. Furthermore, all ectopic or paced beats were automatically separated from sinus rhythm. Computed activation maps are shown for one patient localizing the accessory pathway with an accuracy of 1 cm. CONCLUSIONS: The implemented signal processing pipeline is a powerful tool for selecting target beats for noninvasive activation imaging in WPW patients. It robustly identifies and classifies beats. The small beat to beat variations in the automatic QRS-interval detection indicate accurate identification of the time window of interest.

Action Potentials↗

Computationally efficient noninvasive cardiac activation time imaging.

OBJECTIVE: The computer model-based computation of the cardiac activation sequence in humans has been recently subject of successful clinical validation. This method is of potential interest for guiding ablation therapy of arrhythmogenic substrates. However, computation times of almost an hour are unattractive in a clinical setting. Thus, the objective is the development of a method which performs the computation in a few minutes run time. METHODS: The computationally most expensive part is the product of the lead field matrix with a matrix containing the source pattern on the cardiac surface. The particular biophysical properties of both matrices are used for speeding up this operation by more than an order of magnitude. A conjugate gradient optimizer was developed using C++ for computing the activation map. RESULTS: The software was tested on synthetic and clinical data. The increase in speed with respect to the previously used Fortran 77 implementation was a factor of 30 at a comparable quality of the results. As an additional finding the coupled regularization strategy, originally introduced for saving computation time, also reduced the sensitivity of the method to the choice of the regularization parameter. CONCLUSIONS: As it was shown for data from a WPWpatient the developed software can deliver diagnostically valuable information at a much shorter span of time than current clinical routine methods. Its main application could be the localization of focal arrhythmogenic substrates.

Arrhythmias, Cardiac↗

Ventricular surface activation time imaging from electrocardiogram mapping data.

Non-invasive imaging of cardiac electrophysiology provides a non-invasive way of obtaining information about electrical excitation. An iterative algorithm based on a general regularisation scheme for non-linear, ill-posed problems in Hilbert scales was applied to the electrocardiographic inverse problem, imaging the ventricular surface activation time (AT) map. This method was applied to electrocardiographic data from a 31-year-old healthy volunteer and a 24-year-old patient suffering from a Wolff-Parkinson-White (WPW) syndrome. The objective was to evaluate non-invasive AT imaging of an autonomous sinus rhythm and to quantify the localisation error of non-invasive AT imaging by localising the accessory pathway of the WPW syndrome and a pacing site for left ventricle pacing. The distances between the invasive and non-invasive localisation of the pacing site and the accessory pathway were 8 mm and 5 mm. The clinical case presented, shows that this non-invasive AT imaging approach may enable the reconstruction of single focal events with sufficient accuracy for potential clinical application.

Adult↗

Clinical pathways--can they be used in trauma care. An analysis of their ability to fit the patient.

This study prospectively evaluated the appropriateness and ability of clinical pathways to fit trauma patients in five key conditions, severe head injury, fractured ribs, fractured pelvis, fractured femur and blunt abdominal trauma, who were admitted to a single Level 1 Trauma Centre, between February and July 1999. Each pathway consisted of 14 elements of care divided into observable outcomes. Failure to achieve an outcome resulted in a variance or deviation from the pathway, which was assessed by the number of non-applicable variances. Appropriateness of clinical pathways was assessed by the applicability index (the number of non-applicable variances divided by the potential variances). Critical mismatches occurred when non-applicable variances exceeded 50% of potential variances. 146 patients, with the mean age 41.9 years (S.D. 20.7), mean ISS 11.1 (S.D. 10.7) were enrolled; 18 with severe head injury, 59 with fractured ribs, 13 with fractured pelvis, 20 with fractured femur and 36 with blunt abdominal trauma. Critical mismatch occurred in seven patients. Applicability indexes were 87 for head, 93 for ribs, 92 for blunt abdominal trauma, 91 for femur and 92 for the pelvic pathway. Patient assessment, pain management, skin integrity and patient education were the most appropriate key elements of care, discharge planning, patient satisfaction, treatment and activity were least applicable. This study identified, for the first time, that clinical pathways are clinically appropriate for major trauma conditions.

Abdominal Injuries↗

Intramuscular injection of insulin lispro or soluble human insulin: pharmacokinetics and glucodynamics in Type 2 diabetes.

AIM: The aim of the study was to compare the pharmacokinetics and glucodynamics of insulin lispro and soluble human insulin following intramuscular (i.m.) injection in patients with Type 2 diabetes with secondary failure of sulphonylureas. METHODS: Single 15-U i.m. doses of insulin lispro or soluble human insulin were administered to 16 patients in a two-way, randomized, crossover design. Glucodynamic and pharmacokinetic parameters were determined over 6 h after insulin injection using clamp techniques. RESULTS: Insulin C(max) was significantly higher (971 +/- 217 vs. 659 +/- 141 pmol/l, P < 0.001) and T(max) was significantly shorter (46.9 +/- 27 vs. 94.7 +/- 50.1 min, P = 0.002) with insulin lispro. Glucose infusion rate (GIR) curves showed clear separation 20 min after injection and were significantly greater for insulin lispro during the 40-60, 60-80 and 80-100-minute time intervals. Total glucose infused was only approximately 5% larger with insulin lispro during the 6-h follow-up, due to lower insulinaemia at later time points. The glucose R(max) and TR(max) were not statistically different between insulin treatments. CONCLUSION: This study shows that i.m. injection of insulin lispro is followed by its more rapid absorption, which results in stronger metabolic effect in the first 2 h when compared with soluble human insulin under the same test conditions. Diabet. Med. 18, 562-566 (2001)

Blood Glucose↗

Trauma case management and clinical pathways: prospective evaluation of their effect on selected patient outcomes in five key trauma conditions.

BACKGROUND: This study evaluated the implementation of clinical pathways and case management between July 1998 and July 1999 in five key trauma conditions: severe head injury, fractured ribs, fractured pelvis, blunt abdominal trauma, and fractured femurs presenting to a single trauma service. METHODS: Thirteen key elements of care with expected outcomes were defined for each key trauma condition. Deviations from expected outcome were defined as variances. Attainment of the expected outcomes was measured before (stage 1) and after introduction (stages 2 and 3) of clinical pathways and case management. Nonattained outcomes were quantified and categorized into time of occurrence, and relationship to staff, patient, or system. RESULTS: Two hundred thirty-five patients were studied, with a mean age of 41.8 (SD, 20.6) years and mean Injury Severity Score (ISS) of 11.7 (SD, 11.0). The mean number of observed variances per patient for stage 1 was 51.7 (SD, 43.5); stage 2, 42.3 (SD, 32.9); and stage 3, 23.2 (SD, 21.7) (p = 0.0001 for both stage 1 and stage 2 compared with stage 3). There was a significant improvement in outcomes achieved from stage 1 (92.7%; 95% confidence interval, 92.5-92.9%), to stage 3 (96.7%; 95% confidence interval, 96.5-96.9%). Of the total number of variances seen, 0.2% related to system errors, 25% related to patient factors, and 75.8% related to staff. The proportion of staff-related variances was significantly reduced in stage 3. CONCLUSION: Clinical pathways and case management identified areas in need of remedial action and improved the delivery of patient care to our trauma population. It has set a template for the future management of our trauma service.

Abdominal Injuries↗

An evaluation of trauma team response in a major trauma hospital in 100 patients with predominantly minor injuries.

BACKGROUND: A prospective study of trauma team response and performance at a major trauma service was undertaken between June and September 1998. METHODS: Following activation of the trauma team, the timing of the trauma team's arrival, the subsequent early management of the patient, time to monitoring, X-ray investigation and procedures performed were documented. RESULTS: The study evaluated 100 activations, 76% male, mean age 32 years and 65% were due to road trauma. The team leader, airway doctor and surgical registrar were present on patient arrival in 96%, 90% and 76% of cases, respectively. The airway, procedure and scribe nurses were present on patient arrival in 77%, 97% and 95% of cases, respectively. The radiographer was present in 69% of cases. Comparison between normal and after-hour response revealed little difference in medical and radiographer response, but the after-hour nurse response was significantly worse (P < 0.001). The median time to achieve electrocardiogram monitoring, blood pressure reading, and oxygen saturation tracing was 3 (range: 1-13), 4 (range: 2-20) and 3 (range: 1-21) min, respectively. Intravenous cannulation, phlebotomy and dispatch of bloods occurred at median times of 5 (range: 2-22), 6 (range: 3-23) and 17 (range: 7-40) min. The median times for intubation, chest tube and splintage of fracture were 10 (range: 3-19), 10 (range: 6-14) and 26 (range: 19-55) min, respectively. CONCLUSIONS: The present study identified an excellent multidisciplinary trauma response and provides a template to improve performance in early trauma management.

Accidents, Traffic↗

A prospective study of the performance of the trauma team leader.

This study assessed the performance of the trauma team leader in 50 consecutive trauma resuscitations at Liverpool Hospital over a two-month period. The trauma team consists of intensive care (ICU), emergency, and surgical registrars, three nurses, a wardsman, a radiographer, and a social worker. The team leader position alternates between the ICU and emergency registrar on a fortnightly roster. A panel of specialists experienced in trauma management evaluated 38 aspects of the initial resuscitation. Individual variables received different weightings. The maximum possible score for team leader performance was 80. The mean team leader score was 70.4 +/- 8 (SD). The main deficiencies in the team leader's performances were in their interpersonal communications and in the adequacy of documentation of the history of the injury. In 20% of resuscitations there were failures to completely expose the patient. Medical skills were uniformly well performed. Poor communication with other team members were the main pitfall of the team leader in this study. The team leader score may prove a useful tool in improving the quality of the trauma team.

Clinical Competence↗

Evaluation of the prevalence of drug and alcohol abuse in motor vehicle trauma in south western Sydney.

This study estimated prospectively the prevalence of high drug and alcohol levels in road trauma cases who met the criteria for activation of the Liverpool Hospital's trauma team. Urine analysis of road trauma victims between October 1992 and October 1993 was undertaken for drug and alcohol estimation. A total of 164 drivers were studied. A urine alcohol concentration (UAC) exceeding 0.08 g/dL was detected in 27 drivers (16.5%). Cannabinoids were detected in the urine of 25 drivers (15.2%), in 17 the concentrations exceeded 400 ng/mL. In one instance amphetamine, cocaine and heroin were detected in the same injured driver. Combined use of alcohol with some other drugs was detected in only four drivers. Alcohol and cannabinoid levels were prevalent in the urine of injured drivers in this study, particularly in young males who remain over-represented in the group of injured drivers. In the population surveyed other drugs were rarely detected. The role of cannabinoids in road trauma and the use of cannabinoids in young male drivers will however need to be monitored more extensively.

Accidents, Traffic↗

A modified combination technique for performing diagnostic peritoneal lavage.

Existing open diagnostic peritoneal lavage techniques (DPL) use small bore catheters, through a small lower midline incision or infra-umbilical incision. This study evaluated a modified DPL technique using a 10 mm umbilical incision, with open insertion of a 20 French peritoneal lavage catheter. The catheter has 27 radial side holes in the terminal distal 13 cm, and a female Leur lock connector. Warmed saline is infused via a cystoscopy infusion set. The time required to perform a new technique was studied in 10 patients. The median time to catheter insertion was 2.4 +/- 3.8 min, infusion time 0.75 +/- 0.3 min, effusion time 0.3 +/- 1.7 min, and a median total time of 7.6 +/- 4.2 min (median +/- s.d.). There was no complications. This technique of DPL is cosmetically attractive, much quicker than existing techniques and we have found its initial use encouraging.

Abdominal Injuries↗

IL-1, TNF-alpha and IL-2 production by peritoneal and spleen cells from Schistosoma mansoni infected mice and its potentiation by preimmunization with schistosomal antigens and immunostimulants.

In the present study we tested the effect of immunization with schistosome derived antigens such as frozen-thawed schistosomula in combination with either BCG, liposomes or liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE), on the resistance of mice to infection, and on the function of their macrophages and lymphocytes. Immunization with either F-T schistosomula + BCG or F-T schistosomula + MTP-PE and subsequent infection, resulted in a 2-3-fold increase in adherent peritoneal macrophage-mediated schistosomulicidal activity (SCA). Peritoneal and spleen macrophages from immunostimulant treated and/or immunized animals showed a significant increase in LPS triggered TNF-alpha production, as compared to non-treated controls. The highest increase in TNF-alpha production was achieved after immunization with either F-T schistosomula + BCG or F-T schistosomula + MTP-PE. LPS triggered IL-1 production was elevated in spleen and peritoneal macrophages from F-T schistosomula + BCG treated mice, and also in spleen macrophages treated with F-T schistosomula + MTP-PE. Only immunization with F-T schistosomula + BCG increased ConA-induced spleen lymphocyte proliferation and IL-2 production. Immunization of mice with F-T schistosomula + BCG also induced protection against parasite infection, while F-T schistosomula + MTP-PE failed to do so. Potentiation of antischistosomal resistance seems to require both macrophage and lymphocyte activation which was achieved only when BCG served as an immunostimulant.

Adjuvants, Immunologic↗

The schistosomulicidal activity and the production of IL-1 and TNF-alpha by peritoneal macrophages from infected mice and their potentiation by muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) treatment.

Production of TNF-alpha and IL-1 by adherent peritoneal exudate macrophages (APEM) was monitored for 20 weeks in Schistosoma mansoni infected mice in comparison to their schistosomulicidal activity. LPS-triggered IL-1 and TNF-alpha production by APEM peaked 10 weeks post infection (p.i.) and declined thereafter. The schistosomulicidal activity of APEM also peaked after 10 weeks but remained elevated thereafter. Infected mice were also treated with the immunostimulator liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE) 6 or 10 weeks p.i., and their APEM were tested 4 weeks later. APEM from such treated animals showed elevated IL-1 and TNF-alpha production when treatment commenced 6 weeks p.i., while their schistosomulicidal activity increased when treatment commenced either 6 or 10 weeks p.i. The L-arginine inhibitor, NG monomethyl arginine, markedly inhibited the schistosomulicidal activity but not the IL-1 and TNF-alpha production of APEM. Our results show that monokine production increases during the acute phase of infection and declines during its chronic phase, while macrophage schistosomulicidal activity remains constant throughout. Furthermore, TNF-alpha or IL-1 may play a minor role in APEM mediated killing of schistosomula.

Acetylmuramyl-Alanyl-Isoglutamine↗

On the interaction between macrophages and developmental stages of Schistosoma mansoni: effect of muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) treatment on mice survival and the generation of schistosomulicidal macrophages.

Schistosomiasis is a chronic disease afflicting hundreds of millions of people throughout the world against which there is as yet no effective vaccine. In the present study we tested the effect of the immunomodulator muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) on the survival of Schistosoma mansoni-infected mice and on the induction in them of schistosomulicidal macrophages. Mice exposed to 80 cercariae each and then treated with MTP-PE showed prolonged survival following either single or repeat infection. The treatment with MTP-PE, when initiated 70 days post the schistosome infection, diminished significantly the mortality of infected mice over an observed period of 110 days. In terms of treatment efficacy there was no evident difference between the intravenous and intraperitoneal mode of administration of the drug. MTP-PE treatment significantly reduced granuloma size and markedly diminished liver damaged as judged by the lower levels of alkaline phosphatase in the serum. Such treatment exerted no significant effect on the spleen or liver weight in infected mice nor on the worm burden resulting from either a single or double infection. In infected and non-treated mice, schistosomulicidal macrophages appeared after 8-10 weeks of infection. In infected mice treated with MTP-PE there was an accelerated appearance of such macrophages and these exhibited a greater cidal effect on the schistosomula. These immunostimulatory and life-prolonging effects of MTP-PE on S. mansoni-infected mice might indicate an effect of this reagent on cells involved in the granulomatous process.

Acetylmuramyl-Alanyl-Isoglutamine↗

Age-related development of a heterozygous phenotype in solitary neurons of the homozygous Brattleboro rat.

A single-base deletion in the single-copy vasopressin gene is the cause of diabetes insipidus in the homozygous Brattleboro rat (di/di). It results in the synthesis of an altered vasopressin precursor of which the axonal transport is blocked. Paradoxically, a small number of solitary hypothalamic neurons displays all the immunoreactivities of the wild-type vasopressin precursor (i.e., vasopressin, neurophysin, and a glycopeptide). In the present paper we provide evidence that these neurons have undergone a switch to a genuine heterozygous (di/+) phenotype; i.e., they contain the immunoreactivities of both the wild-type and the mutated vasopressin precursors. In the neural lobe, glycopeptide fibers are also present, showing that axonal transport of the wild-type precursor is restored. Moreover, the number of neurons displaying this di/+ phenotype increases markedly and in a linear way (from 0.1% up to 3% of the vasopressin cells) with age. These findings indicate that after mitotic division has ceased, genomic alterations occur in somatic neurons in vivo. The molecular event generating the di/+ phenotype in the di/di animal could involve a somatic intrachromosomal gene conversion between the homologous exons of the vasopressin and the related oxytocin genes.

Aging↗

Modulation of carcinoembryonic antigen release by HT-29 colon carcinoma line in the presence of different agents.

In this study we followed the effects of various differentiating agents on the expression of carcinoembryonic antigen (CEA) released into the medium by a colon carcinoma cell line HT-29. Butyric acid 1 mM markedly increased the level of CEA (12-fold in comparison to control levels). 12-O-tetradecanoyl-phorbol-13-acetate (TPA) 50 ng/ml and 5-azacytidine 4 x 10(-6) M increased the amount of CEA, 2- and 1.5-fold respectively. On the other hand retinoic acid 10(-5) M, N methyl-formamide 1% and N,N hexamethylene bisacetamide 2.5 mM decreased CEA 2-, 4- and 3-fold respectively. Our results emphasize that various differentiating agents affect CEA levels differently. Thus changes in CEA levels appear not to be reliable as a marker of a more differentiated phenotype.

Acetamides↗