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Biomedical subjects

G Matell

Publications and source records attributed to G Matell.

At least 37 records · Page 2Linked to original sources

Integrating knowledge-based technology into computer aided ventilation systems.

A knowledge-based decision support system for respirator treatment, the KUSIVAR system, has been designed in cooperation between hospital, university and industry. Changes in patient data from respirator and monitoring equipment trigger a computer program that generates advice to the staff concerning e.g. therapy modes and respirator settings using expert systems and process control technology. A prototype has been built on an advanced development workstation, the Unisys Explorer, using the software Knowledge Engineering Environment (KEE). The clinical version is implemented on an Intel 80396-based microcomputer connected on-line via a data-acquisition processor to the respirator. The decision support software is implemented as a module under the Microsoft Windows multitasking environment and communicates with modules for data acquisition, database handling and data presentation by means of message passing using the Windows Dynamic Data Exchange protocol. The modules present coherent user interfaces by conforming to Microsoft Windows standards. The knowledge base is being extensively validated by an expert group in the ICU and the system will be evaluated through animal experiments and clinical studies.

Computer Systems↗

Lung function analysis and optimization during artificial ventilation. A personal computer-based system.

In an intensive care unit a personal computer (PC) application for lung function analysis has been in use for 5 years. The PC system is applied to measure conventional and new parameters for diagnosis and therapy. The primary goal was to find parameters which could be used as optimization indices in optimal control systems for mechanical ventilation. Another clinical application of the PC system was as an automatic controller that stabilizes end-tidal CO2 concentration. The controller and the next application, the optimizer, could be integrated into an optimal control system. Such a system is described and a simulation trial of the integrated structure has demonstrated the potential.

Humans↗

A microcomputer system for on-line monitoring of pulmonary function during artificial ventilation.

Standard monitoring of the artificially ventilated patient in the intensive care unit (ICU) and during anaesthesia includes repeated determinations of arterial blood gases, airway pressure and expired volume. However, there is a need for more extensive monitoring of the critically ill ventilator treated patient, and this is possible by better utilization of modern technology. Information on a variety of variables related to both pulmonary mechanics and gas exchange has long been accessible in the lung-function laboratory. Small, inexpensive microcomputers (PCs), accurate and fast bedside monitors and modern ventilators have also made this information directly available to the ICU staff. This paper describes a microcomputer (PC-XT) system for on-line bedside monitoring of pulmonary function. The microcomputer receives airway pressure, gas-flow and timing signals from the ventilator and signals for carbon dioxide concentration from an infrared analyzer. Data related to pulmonary mechanics and gas exchange are derived and displayed on the computer screen, both numerically and as graphs. In studies of ten artificially ventilated patients the coefficients of variation (CV) were below 10% for directly obtained variables (tidal volume, airway pressure, end-tidal and mixed expired carbon dioxide, carbon dioxide production, airway dead space), whereas the derived variables (compliance, phase III carbon dioxide slope) were associated with greater variability, with CVs ranging from 1.3 to 24% (median 6.25% and 8.65% respectively). The accuracy in estimating dead space variations was checked in two ventilator-treated patients by adding known dead space volumes. Simple regression analysis yielded an r value of 0.98 indicating adequate correctness of measurements and calculations.

Airway Resistance↗

Knowledge base design for decision support in respirator therapy.

A knowledge base is built for decision support applied to respirator therapy (the KUSIVAR project). The knowledge representation is object-oriented using frames to store multiple forms of knowledge: variable descriptions, transformation tables, rules and mathematical models. The system is data-driven, generating and displaying advice automatically triggered by changes in data from the respirator and the patient. The inferenceing mechanism is forward-chaining i.e. a rule is evaluated as soon as it's condition is satisfied. Temporal aspects of the reasoning are represented by a number of mechanisms, among others limited validity times for data, trend analysis and mathematical models. The knowledge base is organized according to disease groups and decision situation which simplifies knowledge acquisition and improves response times since it enables the system to focus on a limited set of rules in each situation. To test the feasibility of the system design a prototype has been built using Knowledge Engineering Environment (KEE) from Intellicorp on an Explorer workstation from Unisys. The production system, which is interfaced to a Siemens Elema Servo Ventilator 900C, is currently being implemented under the Microsoft Windows multitasking environment on a microcomputer based on an Intel 80386 processor.

Decision Support Techniques↗

Computer simulation of a patient end tidal CO2 controller system.

A computer model of the patient end tidal CO2 controller system has been developed and tested in simulation trials. It is intended to aid in finding the appropriate PI (proportional-integral) controller settings by means of computer simulation instead of real experiments with the system. The latter approach is costly, time consuming and sometimes impossible to perform. The simulator consists of two equations: the patient equation and the PI controller equation. The software has been written in the C language and can be run on an IBM-PC/XT. Some examples of the simulation trials, illustrating the choice of controller settings, are given.

Carbon Dioxide↗

In vitro culture of human thymic epithelial cells in serum-free media.

Epithelial cells from human thymus were cultured in vitro at various serum concentrations and under defined serum-free conditions. A total of 238 cultures from 46 thymuses (MG and normal) were analyzed. Cells from fresh thymic tissue were explanted either as fragments or single cells after enzyme treatment. Serum-free as well as fetal calf serum (FCS) containing media based on Dulbecco's minimal essential medium and Ham's F-12 (DMEM/F-12) were found to be superior to MCDB 151 based serum-free media combinations, for the selective growth of thymic epithelial cells. In contrast, cultures based on RPMI 1640 medium supplemented with 1% FCS or more showed less epithelial cell selectivity and also supplement Ultroser G gave less fibroblast contamination. In serum-free media containing less than 0.1 mM ionic Ca, the cells had a smaller surface area and appeared more angular and also contained less keratin as compared to culture media with higher calcium contents. The development of serum-free conditions for in vitro growth of human thymic epithelial cells free of fibroblast contamination will facilitate studies of growth and maturation of the epithelial cells as well as investigations of their possible role in the development of myasthenia gravis.

Cell Communication↗

B-cell compartment in the thymus of patients with myasthenia gravis and control subjects.

An increased number of CD19, 20, and 22 positive B cells, compared to the number of Ig-positive cells, is regularly found in the thymic medulla of normal thymus, suggesting that a B-cell population normally resides in thymic medulla that lacks Ig expression. However, some of the CD20-positive cells seem to co-express keratin and MR19, suggesting an epithelial origin. The medullary B cells found in normal thymus could be precursors of the tumor cells in "mediastinal clear cell lymphomas of B-cell type." In follicular hyperplasia in MG, the medullary epithelial network is deformed and partly destroyed, and the interlobular/perivascular spaces are expanded. Follicles with follicular dendritic cells are found in both interlobular/perivascular spaces and "punched out" lesions in the medullary epithelium. The B cells are greatly increased in MG thymuses compared with control thymuses. These cells are found mainly in the follicles, but they are also dispersed in the medulla and the interlobular/perivascular spaces. The immunophenotype and distribution of B and T cells as well as the follicular dendritic cells in the hyperplastic follicles are similar to those of reactive follicles in lymph nodes. Our findings are consistent with the contention that in MG there is an autoimmune activation of B cells that normally reside in the thymic medulla. This activation leads initially to follicular hyperplasia in the medullary epithelium with destruction of medullary epithelial cells. The prolonged immune reaction in the autoimmune process induces a fibronectin-rich stroma formation and increased vascularization. The result is a remodeling of the thymic architecture with expansion of the perivascular/interlobular spaces replacing the destroyed medulla.

Antigens, Differentiation↗

Immunosuppressive drugs: azathioprine in the treatment of myasthenia gravis.

Azathioprine may be tried for treatment of severe myasthenia gravis, in a dose of 2 mg/kg BW. With careful monitoring the side reactions may be controlled. The therapeutic response will occur after a time delay of 4-8 months. About one-third of patients with type II MG (severe, late onset, HLA B8-) will proceed to a complete but azathioprine-dependent remission, and the remaining two-thirds to a marked improvement. In type I MG (early onset, HLA B8+) azathioprine is less effective but will help keep down the need for corticosteroids or plasmapheresis.

Azathioprine↗

Failing transcervical thymectomy in myasthenia gravis. An evaluation of transsternal re-exploration.

Twenty cases of failing transcervical thymectomy are reported. They were selected for transsternal re-exploration from a series of 95 patients who had previously undergone transcervical thymectomy because of myasthenia gravis (MG). A specific method for pre-operative detection of remnants of the non-tumorous thymic gland is lacking, but the applied clinical selection criteria were so far reliable: generalized, disabling, fluctuating MG despite cholinesterase inhibitor and/or immunosuppressive treatment, and no or inconsistent improvement after transcervical thymectomy. At transsternal re-exploration the commonest findings were intact lower thymic lobes with persistent venous drainage into the brachiocephalic vein. Presence of thymic tissue was histologically confirmed in all the excised specimens (weight range 10-60, mean 23 g), and the examination showed thymic hyperplasia in 18 cases, fatty involution of the gland in two, and a lympho-epithelial thymoma in one case. The re-operation was followed by objectively registrable improvement in all but one of the 20 patients during observation periods of 8-75 (mean 21) months. There was statistically significant reduction in disability scores (means 8.2-4.9) and in need for anticholinesterase medication (to 67% of pretreatment dose). Immunosuppression became unnecessary in 6 of 11 patients and could be reduced in 4 patients. The incidence of failure in transcervical thymectomy was alarmingly high (27%), and more re-operations are anticipated. Since the transcervical approach involves a high risk of incomplete thymectomy, its use should be abandoned. However, in most of the patients with re-operation, subsequent progress has been sufficiently promising for advocacy of sternotomy whenever the clinical criteria of failure are fulfilled.

Adolescent↗

Differential ventilation in acute bilateral lung disease. Influence on gas exchange and central haemodynamics.

Eight patients with acute respiratory failure (ARF) due to diffuse and rather uniform lung disease were intubated with a double-lumen bronchial tube and ventilated in the lateral decubital position by two synchronized ventilators. Ventilation of each lung was individually adjusted to match the expected regional blood flow (differential ventilation). When ventilation with equal volumes (i.e. 50% of tidal volume to each lung) was performed, a 19% reduction of venous admixture (P less than 0.001) and a 22% increment in arterial oxygen tension (P less than 0.001) were seen. Comcomitantly, the cardiac output increased by 17% (P less than 0.001), to which a reduced pulmonary vascular resistance may have contributed. The net result was a 14% increment of the oxygen availability (P less than 0.001). An attempt to go further, giving 2/3 of the tidal ventilation to the dependent lung, was made on six of the patients. However, this ventilatory pattern did not further improve the gas exchange and also had detrimental effects on the haemodynamics. It is concluded that differential ventilation with equal tidal volumes in the lateral position can substantially improve gas exchange and central haemodynamics in patients with ARF due to diffuse lung disease.

Acute Disease↗

Gm allotypes in Swedish myasthenia gravis patients.

Gm phenotype frequencies were examined in 112 Swedish myasthenia gravis patients. The G1m 1,2,3 phenotype frequency in the total patient material did not differ significantly from that found in the normal population. However, when patients were subdivided, three different patient groups were observed with regard to Gm1 frequency: (1) Thymoma patients having a low frequency of Gm1, (2) Non-thymoma patients with a mild disease having a low frequency of Gm1 and (3) Non-thymoma patients with a severe disease having a high frequency of Gm1. When patients were subdivided according to presence or absence of HLA-B8 and Gm1 respectively, severe symptoms were less frequent in the HLA-B8+, Gm(-1) group as compared to the HLA-B8+, Gm(+1) group. Furthermore, there was an increased frequency of sera with anti-immunoglobulins not inhibitable by pooled control immunoglobulins.

Antibodies, Anti-Idiotypic↗

Role of penicillamine for the induction of myasthenia gravis.

Penicillamine and derivatives of this drug were tested for lymphocyte-activating properties. D- as well as L-penicillamine induced in vitro DNA synthesis in mouse splenocytes, whereas D-penicillamine methyl ester, N-acetyl-D-penicillamine and D-penicillamine disulfide were devoid of stimulatory properties. Lymphocytes from athymic mice were also responsive. However, we were unable to detect an increased antibody secretion in mouse spleen cell cultures exposed to penicillamine. Human peripheral blood lymphocytes from healthy individuals as well as from patients with penicillamine-induced myasthenia gravis only gave minor proliferative responses after in vitro penicillamine exposure. Furthermore, there were no differences in proliferative capacity between these two groups. Cultivated human peripheral blood or spleen cells were not activated to antibody secretion in the presence of penicillamine. There were no signs of myasthenia gravis using single-fiber electromyography recordings in patients with rheumatoid arthritis being on penicillamine treatment or in mice from several different mouse strains receiving penicillamine in their drinking water. However, NZB/NZW hybrid mice receiving penicillamine had increased amounts of antinuclear and anti-dsDNA antibodies.

Animals↗

Immunological studies on human thymus. Occurrence and distribution of immunoglobulins and immunological receptors in myasthenia gravis and control patients.

Suspended cells and tissue sections from myasthenia gravis (MG) and control thymuses were characterized for surface expression and histological distribution of immunoglobulin (Ig) and receptors for sheep erythrocytes (SE), the Fc part of IgG (Fc gamma) and of IgM (Fc mu) and complement factors C3b and C3d (CR). In sections the cortical areas from both MG and control thymuses expressed SE as well as Fc gamma receptors, whereas medullary areas only showed weak SE binding. In contrast to control patients, MG thymuses also contained Ig+ cells confined to nodular areas of the thymic medulla. These nodules stained for both IgG and IgM, and were polyclonal with respect to light chains. In several cases IgD was found as well. In addition, the nodular areas were positive for C3b and C3d receptors. In serial sections, these Ig+ CR+ nodules corresponded to morphologically characteristic lymphoid follicles. Such B cell follicles were observed in variable numbers in all MG thymuses, whether hyperplastic or with normal histology. Five thymomas gave heterogeneous results with regard to immunological markers. Comparison of methods showed that receptor and Ig indication on sections was more sensitive than corresponding tests on thymus cells in suspension.

Adult↗

HLA-A, -B, -C and -D antigens in male patients with myasthenia gravis.

HLA-A, -B, -C and -D antigens were determined in 54 male Myasthenia Gravis patients. A significant increase of the B8 antigen frequency was found among patients with an onset of the disease before the age of 35. No significant increase was found among the D antigens. In a combined male and female material with an early age at onset, thymic hyperplasia was correlated to the presence of HLA-B8.

Adult↗