Search PubMed⌕ Search

Biomedical subjects

G Matell

Publications and source records attributed to G Matell.

At least 19 recordsLinked to original sources
PubMed1992

Beta 2-adrenergic receptor antibodies in myasthenia gravis.

Although autoantibodies against the nicotinic acetylcholine receptor are the characteristic feature of the autoimmune disease myasthenia gravis (MG), no strong correlation is found between the autoantibody titer and the degree of clinical severity. Numerous studies have attempted to detect the presence of other autoantibody populations that might have a role in the pathology of the disease. We report, for the first time, that 18% of the MG patients we screened have antibodies in their serum to a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor (residues 172-197). Affinity purified antibodies to the beta 2-adrenergic receptor peptide 172-197 reacted with the human beta 2-adrenergic receptor protein obtained from transfected E. coli cell membrane extracts, but did not cross-react with the human AChR. Sufficient material was obtained from nine MG patients and it was found that the gamma globulin fraction from these patients immunoprecipitated the receptor, and that affinity purified IgG to peptide 172-197 competed for receptor binding with the beta-antagonist iodo-cyanopindolol. Using truncated peptides or amino acid modification procedures, no immunodominant B-cell epitope could be detected within region 172-197. Thus, a subpopulation of MG patients possesses anti-beta 2-adrenergic receptor antibodies which are a distinct set of autoantibodies with possible pharmacological activity.

Amino Acid Sequence↗
PubMed1991

Multivariable optimization of mechanical ventilation. A linear programming approach.

The proposed method aims at improved ventilatory care with reduced morbidity. It combines two important aspects of mechanical ventilation: gas exchange and lung mechanics. A single criterion was selected as optimization index of lung trauma: peak respiratory power (PRP) defined as the maximum product of pressure times flow during inspiration. Arterial blood gases reflect gas exchange and constitute the constraints of the problem. The constraints as well as the optimization index are expressed as linear functions of the input variables (frequency of breathing, tidal volume, and positive end expiratory pressure). A linear programming approach can therefore be used to determine the values of input variables that minimize PRP and at the same time keep arterial blood gases within the prescribed limits. The coefficients of the constraints and the optimization index equation are found by manipulating input variables in order to obtain four different values of PaO2, PaCO2 and PRP (there are four coefficients in each equation). The coefficients can then be calculated and the optimization procedure run. In a pilot study 5 patients suffering from diseases of varying pulmonary pathology were investigated with this method. In 4 out of 5 the ventilator treatment improved in terms of blood gas values (mean increase in PaO2 was 4.7%) and reduction of mechanical load on the lungs (mean PRP reduction was 20%). Lower PRP is accompanied by lower mean power and pressure values, which results in increased cardiac output. Presently, the main problem is the time it takes to determine the patient coefficients (approx one hour), a procedure that needs to be simplified.

Acute Disease↗
PubMed1991

Mechanical ventilation in medical and neurological diseases: 11 years of experience.

Mechanical ventilation (MV) is imperative in many forms of acute respiratory failure (ARF). The aim of this work was to review all episodes of MV in a Medical Intensive Care Unit (MICU) during the 11-year period 1976-1986. Four per cent (n = 1008) of 24,899 admissions to the MICU were treated with MV. The mean age of ventilator-treated patients was 53 +/- 18 years, and obviously it increased during the period of study. The average duration of MV was 4.7 d. MICU mortality, hospital mortality and 2-year mortality rates for patients subjected to MV were 33%, 38% and 46%, respectively. The mortality rate did not change during the study period. Cerebrovascular and malignant diseases carried the highest mortality rates, 75 and 79%, respectively, whereas mortality in patients ventilated because of drug overdose (n = 313) was only 2%. The results of this study confirm previously published findings concerning the outcome of MV, and we conclude that the effects of MV remain discouraging in medical and neurological patients. Improved quality of ventilator therapy and monitoring, as well as continued research directed at the causes of ARF, are equally important in reducing the mortality in ARF.

Adolescent↗
PubMed1990

Diagnostic utility of flumazenil in coma with suspected poisoning: a double blind, randomised controlled study.

OBJECTIVE: To assess the diagnostic value and safety of the benzodiazepine antagonist flumazenil in patients with coma of unclear origin with suspected poisoning. DESIGN: Double blind, placebo controlled, randomised study. SETTING: Intensive care unit at a major teaching hospital. PATIENTS: 105 Unconscious adults admitted consecutively with suspected drug overdosage during 18 months from a total of 362 cases of poisoning. Exclusion criteria were pregnancy, epilepsy, obvious poisoning with drugs identified unequivocally from information from relatives or others as other than benzodiazepines, and coma score greater than 10 on a scale graded from 4 to 20. Patients were allocated randomly to receive flumazenil (21 men and 32 women) or placebo (25 men and 27 women). INTERVENTIONS: Intravenous injection of flumazenil (10 ml, 0.1 mg/ml) or placebo (10 ml vehicle alone) given double blind over three minutes. MAIN OUTCOME MEASURES: Serum and urine concentrations of benzodiazepines, antidepressants, and several other agents; blood gas tensions; standardised evaluation on admission and five minutes after the injection by means of coma scale score and urgent diagnostic or therapeutic interventions indicated according to the history and clinical examination; standardised interview after the injection to try to ascertain further information; and adverse reactions. RESULTS: Benzodiazepines were found in the serum in 36 of the 53 patients in the flumazenil group and in 37 of the 52 who received placebo. The average coma scale score increased significantly after injection in the flumazenil group (6.4 v 12.1, p less than 0.001) but not in the placebo group. In the flumazenil group several interventions were rendered unnecessary by the injection: gastric lavage and urinary catheterisation (19 patients each), intubation (21), artificial ventilation and computed tomography of the brain (three patients each), blood culture and lumbar puncture (one patient each), and electroencephalography (two). In the placebo group the indications for these procedures did not change in any patient after injection. The 95% confidence interval for the difference in reduction of the frequency of indications for gastric lavage after injection between the two groups was 21% to 51%, that for intubation 25% to 55%, and that for urinary catheterisation 21% to 51%. In the flumazenil group 21 patients gave valuable information on their drug ingestion within 10 minutes after injection compared with only one in the placebo group (p less than 0.001). Nine adverse reactions were recorded in the flumazenil group, eight of which were graded as mild and one severe. The safety of the antagonist was acceptable, even though 60% of the patients in the flumazenil group had multiple drug poisoning including benzodiazepine. No epileptic seizures or arrhythmias were recorded. CONCLUSION: Flumazenil is a valuable and safe differential diagnostic tool in unclear cases of multiple drug poisoning.

Adolescent↗
PubMed1990

Different HLA DR-DQ associations in subgroups of idiopathic myasthenia gravis.

We have investigated the HLA-DRB and -DQB gene polymorphism in 131 myasthenia gravis (MG) patients. The HLA genotypes in these patients were assigned by means of restriction fragment length polymorphism (RFLP)-defined DR-DQ haplotypes, correlating to serologic HLA class II typing. Using this technique we could, among randomly selected non-thymomatous (NT)-MG patients, confirm the strong association to DR3, and 70% of the patients were found to carry a specific DR3-positive DR-DQ haplotype, T-3.1. Furthermore, an analysis of T-3.1- NT-MG patients revealed that 59% were T-4.1+ (DR4, DQw8). Thymic hyperplasia was found in approximately 85% of the T-3.1+, as well as of the T-4.1+/3.1- patients. As previously observed, we found a clear dominance of females among the T-3.1+ NT-MG patients. However, among T-4.1+/3.1- patients, males were as common as females. Furthermore, the T-4.1+ patients were significantly older at the onset of disease than those who were T-3.1+. In female MG patients, the DRw15-Dw2-positive haplotype T-2.1 was strongly correlated with the presence of thymoma (T-MG). These data indicate that the HLA associations in early vs late onset of NT-MG are different, and that female patients with and without thymoma differ from each other with regard to HLA markers. Thus, at least three different HLA DR-DQ associations are found in subgroups of idiopathic MG.

Female↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1987

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↗
PubMed1978

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↗
PubMed1978

No significant correlation of HLA-B8 and amount of antibodies directed to acetylcholine receptor protein in patients with myasthenia gravis.

Forty patients with myasthenia gravis were HLA tissue typed and the amount of anti-acetylcholine receptor protein antibody determined. Sera from seven patients were tested for antibody titer by repeated determinations and the serum concentration was found to be stable. Patients with thymoma had higher titers than patients with normal thymus histology or hyperplasia. Individuals with thymoma lacking HLA-B8 were found to have a higher concentration of antibodies than HLA-B8 negative individuals with hyperplasia. No statistically significant differences were obtained when comparing the amount of antibody in HLA-B8 positive and negative individuals. Titers in patients subjected to thymectomy more than 8 years before sampling did not deviate from those in non-thymectomized myasthenics.

Acetylcholine↗
PubMed1978

Determination of acetylcholine receptor antibody in myasthenia gravis: clinical usefulness and pathogenetic implications.

Antibodies to cholinergic receptor structures were found in 75% of 76 Finnish and 93% of 175 Swedish patients with myasthenia gravis. The amount of antibodies showed a positive correlation to the severity of the disease, and was reduced during immunosuppressive treatment, and by thymectomy. Thymoma patients had high values. The antibody was also found in the cerebrospinal fluid. Two healthy newborn babies of myasthenic mothers had antibodies during the first weeks of life, in spite of no clinical symptoms. The occurrence of IgM antibodies before IgM antibodies in two patients during the early stages of myasthenia gravis suggests that the antibody is not a primary cause of the disease.

Adrenocorticotropic Hormone↗