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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 91 records · Page 5Linked to original sources

Lung recruitment at birth does not improve lung function in immature lambs receiving surfactant.

BACKGROUND: In mature animals with surfactant deficiency induced by lung lavage, the therapeutic effect of exogenous surfactant is enhanced by a lung recruitment maneuver. We then tested whether a lung recruitment maneuver at birth immediately before surfactant treatment would improve lung function also in preterm lambs with surfactant deficiency due to immaturity. METHODS: Ten newborn lambs with a gestational age of 127 days were randomized to receive surfactant either before the first breath or immediately after a lung recruitment maneuver consisting of five sustained inflations of 8, 16 or 32 ml/kg. Functional residual capacity was measured by sulfur hexafluoride washout, and inspiratory capacity as well as maximal compliance were obtained from a static expiratory pressure-volume curve after the lungs had been inflated to 35 cm H2O. In addition, blood gases were obtained. Measurements were made at 15, 45, 175, 135, 170 and 230 min after birth. Post mortem histological examinations of the lungs were performed in a blinded fashion. RESULTS: The lung recruitment maneuvers did not improve oxygenation. Inspiratory capacity, static compliance and functional residual capacity at 4 h, as well as post mortem intrapulmonary air volume, had an inverse relation to the size of inflations given at birth. There was also a negative correlation between size of inflations at birth and response to surfactant therapy, as assessed by lung microscopy. CONCLUSION: Lung recruitment at birth does not improve the response to surfactant in immature lambs, but may instead have an adverse effect on lung function and morphology.

Animals↗

Circulating human antisperm antibodies recognize prostasomes.

PROBLEM: The presence of naturally occurring antisperm antibodies (ASA) is a well-known cause of infertility in men and women, but the antigens for these antibodies are usually poorly characterized. Prostasomes, organelles secreted by human prostatic acinar cells and expelled into the seminal plasma at ejaculation, can adhere to sperm cells. Thus, we have examined whether prostasomes could be an antigen for ASA. METHOD OF STUDY: We have studied the reactivity of chicken antiprostasome antibodies with sperm cells in an agglutination test and conversely the reactivity of serum positive for ASA from 20 infertile patients, with spermatozoa using flow cytometry and with purified prostasomes using enzyme-linked immunosorbent assay. RESULTS: The chicken antiprostasome antibody caused agglutination of sperm cells similarly to the agglutination observed with patients' sera. All of these patients' sera contained IgG antibodies against prostasomes. CONCLUSIONS: The high percentage of patients with antiprostasome antibodies in this study shows that prostasomes could be one of the major targets for ASA.

Animals↗

The mandibular condyle in juvenile chronic arthritis patients with mandibular hypoplasia: a clinical and histological study.

In 12 JCA patients with severe mandibular hypoplasia, who all strongly demanded early treatment, 21 mandibular condyles were replaced by costochondral grafts. All of them had radiographic morphological changes in the mandibular condyles with varying degrees of destruction of the articular cartilages. Severe pathological changes in the lower joint compartments were consistently observed at surgery. Hence, the lower joint compartments were obstructed with granulomatous tissue, whereas the upper compartments were without macroscopic pathological changes. These findings indicated a polarized involvement of the temporomandibular joint (TMJ) in juvenile chronic arthritis (JCA). The extent of condylar articular surface destruction at histological examination varied from focal to total cartilage destruction. Inflammation of the subchondral bone marrow was a frequent finding. In spite of considerable arthritic destruction of the condyles, only one patient had TMJ pain, while a restricted mouth opening capacity was a more frequent finding. Thus, TMJ pain did not seem to constitute a reliable symptom of serious arthritic destruction of the mandibular condyle.

Adolescent↗

Contact between a polymer and whole blood: sequence of events leading to thrombin generation.

The mechanism by which thrombin is generated on a polymer surface in an extracorporeal circuit is not yet fully understood. To address this question we have developed an in vitro chamber model in which whole blood containing heparin (1 IU/mL) comes in contact with a commonly used biomaterial, polyvinyl chloride (PVC). Incubation of blood in the chamber for 60 minutes at 37 degrees C resulted in the binding of platelets to the material surface and the generation of thrombin-antithrombin complexes. Corn trypsin inhibitor, a specific inhibitor of factor XIIa, inhibited this thrombin-antithrombin complex generation in blood in contact with PVC, which is not considered an efficient activator of factor XII. The addition of the glycoprotein IIb/IIIa inhibitor Ro44-9883 abrogated platelet binding and aggregation and resulted in decreased generation of thrombin-antithrombin complexes. Thrombin-antithrombin generation was also negligible in platelet-rich plasma but could be partially restored in the presence of erythrocytes. Taken together, these data are compatible with a model in which thrombin generation is triggered by factor XII. The response to contact with PVC appears to begin with a low-grade generation of thrombin that involves both erythrocytes and leukocytes and that activates platelets, followed by the activation of a platelet-dependent amplification loop that produces most of the thrombin.

Acetates↗

Long-term clinical outcome in patients with glutathione synthetase deficiency.

OBJECTIVE: The objective was to determine the long-term clinical outcome and the effects of treatment of patients with glutathione synthetase (GS) deficiency (n = 28). METHODS: The diagnosis was based on demonstration of a marked decrease in GS activity in erythrocytes or cultured fibroblasts in all patients and was supported by finding a decrease in erythrocyte or fibroblast glutathione, presence of 5-oxoprolinuria, or both. The treatment varied but usually included correction of acidosis and supplementation with vitamins C and/or E. RESULTS: Sixteen patients were severely affected with neurologic symptoms such as seizures and psychomotor retardation; 7 had died at the time of the study. None of the severely affected patients had been treated with both vitamins C and E from the neonatal period. No significant difference was found in GS activity between patients with or without neurologic symptoms or in erythrocyte or fibroblast glutathione levels. Five patients had recurrent bacterial infections. CONCLUSION: On the basis of clinical symptoms, patients with GS deficiency can be classified into 3 phenotypes: mild, moderate, and severe. Our results indicate that early supplementation with vitamins C and E may improve the long-term clinical outcome.

Acidosis↗

Regional cerebral blood flow in normal individuals aged 40, 75 and 88 years studied by 99Tc(m)-d,l-HMPAO SPET.

Age-related changes in cerebral blood flow (CBF) were examined with [99Tc(m)]-d,l-hexamethylpropylene amine oxime (HMPAO), using a single photon emission tomography (SPET) gamma camera system equipped with a high resolution collimator, in 33 normal individuals in three age groups: 40 years old (n = 11), 75 years old (n = 9) and 88 years old (n = 13). A standard activity of 1000 MBq [99Tc(m)]-d,l-HMPAO was administered. Regional CBF (rCBF) (relative to cerebellar counts) was quantified in 28 grey and white matter regions. The mean rCBF of all the regions was 0.80 (95% confidence interval [CI] 0.77-0.83) in 40 year olds, 0.77 (0.74-0.80) in 75 year olds and 0.76 (0.73-0.78) in 88 year olds. rCBF in the hippocampus, angular and cingular gyri, and frontal association and motor cortices was 5-10% lower in the 75 and 88 year olds than in the middle-aged subjects (P < 0.05). The annual reduction in rCBF was 0.10% between the ages of 40 and 75 years and 0.13% between the ages of 75 and 88 years. The reduction in rCBF in the hippocampus rose from 0.14% between the ages of 40 and 75 years to 0.33% between the ages of 75 and 88 years. The mean rCBF in all 33 individuals showed no sex-related differences.

Adult↗

Neonatal screening for congenital adrenal hyperplasia: 17-hydroxyprogesterone levels and CYP21 genotypes in preterm infants.

OBJECTIVE: Neonatal screening for congenital adrenal hyperplasia (CAH) among preterm infants is complicated by the fact that healthy preterm infants have higher levels of 17-hydroxyprogesterone (17-OHP) than term infants, resulting in a higher false-positive rate. Even when gestational age-related cutoff levels after ether extraction were used, the false-positive cases primarily comprised preterm infants. The aim of the study was to optimize the procedure for neonatal screening for CAH in preterm infants. METHODS: The 17-OHP levels in 6200 preterm infants were correlated to the gestational age. We also calculated the number of recalls for different putative cutoff levels of the 17-OHP by direct assay and after extraction in 1275 preterm infants who represented the most elevated cases in a population of approximately 30 000 preterm infants. The CYP21 genotypes and screening levels were determined in the 12 preterm infants with CAH diagnosed since the start of screening. The effect of possible interfering factors such as gestational age, neonatal stress, and prenatal glucocorticoid treatment for pulmonary maturation was studied. RESULTS: The extraction procedure did not significantly improve the sensitivity or specificity of the screening, whereas it delayed the day of recall from 8 to 13 days (median). We could not demonstrate any systematic influence of the studied stress factors or the prenatal glucocorticoid treatment on the 17-OHP screening levels. In the patients with CAH, the 17-OHP levels correlated better with disease severity than with the degree of prematurity. CONCLUSIONS: On the basis of these results, we omitted the extraction step and changed the cutoff levels in the Swedish screening program for preterm infants. We chose to use a cutoff level of 400 nmol/L plasma in infants who were born before week 35 and 150 nmol/L for infants who were born in weeks 35 and 36. For detecting more patients, the cutoff level would have to be much lower, which would result in a number of false-positive tests that we consider to be unacceptably high. It is clear that neonatal screening cannot detect all infants with CAH. Some milder forms of the disease, just like in the past, will have to be diagnosed on the basis of clinical signs and symptoms.

17-alpha-Hydroxyprogesterone↗

The effect of hyaluronan on bone and soft tissue and immune response in wound healing.

BACKGROUND: The aims of this study were to investigate the anti-inflammatory effect and the effect on bone regeneration of hyaluronan in surgical and non-surgical groups. METHODS: In each of 15 individuals, 2 teeth with defects of similar character and magnitude in the upper or lower jaw were chosen. There were at least 2 teeth between the test and the control sites. In the surgical group, a bioabsorbable membrane was used for both test and control sites, and hyaluronan was placed in the intrabony pocket of the test site. In the non-surgical group, the periodontal pockets were scaled and hyaluronan was administered 3 times with an interval of 1 week in the test pockets. Alveolar bone height and bone healing patterns were analyzed using digital intraoral radiographs. Measurements of bone height were performed in the original digital black-and-white radiographs to obtain quantitative data on bone gain or loss. Bone healing patterns were studied with color-coded radiographs, using specially designed software in a personal computer with subsequent combinations of radiographs. Gingival crevicular fluid immunoglobulin (Ig)G, C3, and prostaglandin E2 (PGE2) responses; periodontal probing depth; bleeding on probing; and the presence of plaque were studied to evaluate the anti-inflammatory effect. Data were obtained at baseline before treatment, and at 2 weeks, and 1, 3, 6, and 12 months after treatment. RESULTS: For the surgical treatments, bone height was increased in the test group treated with hyaluronan (mean value 2.2%, corresponding to an average increase of approximately 0.5 mm) and reduced in the control group (mean value -1.8%, corresponding to an average decrease of approximately - 0.4 mm) (P<0.05) after 12 months. For the non-surgical treatments, bone height was reduced by a mean value of -1.1% (corresponding to an average decrease of approximately -0.25 mm) in the test group treated with hyaluronan and -3.3% (corresponding to an average decrease of approximately -0.75 mm) in the control group after 12 months (N.S.). According to the digital color-coded radiographs, the test sites in the surgical and non-surgical groups showed apposition of bone minerals. Immune responses showed no differences during the 12 months studied for the surgical and non-surgical sites. Mean periodontal probing depths were reduced between 2.5 mm and 4.1 mm in the surgical and non-surgical groups. CONCLUSIONS: The observed difference in bone height between test and control sites in the surgical group after 12 months was less than 1 mm, which was only detectable on radiographs. No statistical difference was found on radiographs in the non-surgical group, where a decrease in bone height was found for both groups after scaling. Probing depth reduction after the surgical treatment, as well as after scaling and root planing, was as expected. Hyaluronan in contact with bone and soft tissues had no influence on the immune system in this study. Further studies are needed to determine the extent to which hyaluronan can lead to clinically significant healing of periodontal lesions.

Absorbable Implants↗

Avian antibodies can eliminate interference due to complement activation in ELISA.

Antibodies derived from egg yolk offer many advantages over mammalian antibodies in several aspects. Chicken antibodies do not activate the human complement system and are sometimes a more suitable choice in designing solid-phase immunometric assays than mammalian antibodies. The material often recommended for immunological assays is serum. A freshly drawn serum sample contains an active complement system, which is inactivated during storage. Mammalian antibodies used in most immunological assays may activate the human complement system. Activated complement components will bind to the antibodies thereby partly block the antibody binding epitopes. We show that an active complement system in undiluted samples reduce the absorbance values by approximately 50 % when using goat antibodies but not when using chicken antibodies. This difference will cause erroneous test results that will vary depending on the handling of the samples. Chicken antibodies can be used to eliminate this interference problem.

Animals↗

Extraction of IgY from egg yolk using a novel aqueous two-phase system and comparison with other extraction methods.

Egg yolk is an important source of antibodies. The biggest obstacle for isolation of chicken antibodies (IgY) is the removal of lipids, which are present in abundance in egg yolk. We have used a two-phase system to separate egg yolk. The use of an aqueous two-phase system with phosphate and Triton X-100 made separation of lipids and water-soluble proteins possible. Lipids are extracted into the detergent-enriched top-phase, whereas IgY is isolated in the phosphate-enriched bottom-phase. The phosphate:triton system was characterised and optimised using various experimental designs. For the optimised model, the yield of IgY was kept above 97% (11.1-14.9 mg IgY/g egg yolk recovered). The amount of lipids in the bottom-phase was kept below 25% of the total content in the egg yolk added. Hence, the model described provides a method for extracting the IgY-fraction with a high yield and relatively low lipid content.

Animals↗

Autoantibodies to prostasomes as new markers for prostate cancer.

Prostate cancer is one of the leading causes of cancer-related death among men. Given the varying clinical course and the long natural history of the disease, it is important to have good diagnostic and prognostic markers. Prostate specific antigen (PSA) is currently the best marker for the detection of prostate cancer, but in many cases it does not reveal whether metastases have appeared. Since metastases of prostate cancer release prostasomes, which are immunogenic secretory granules of both normal and neoplastic prostate cells, we checked whether anti-prostasome antibodies will appear when the cancer is metastasing. In a pilot study, all 13 patients with serum PSA between 50-500 microg/L had anti-prostasome antibodies, while 39 healthy controls with low PSA values showed background values. There was no overlapping, i.e. the upper range value of controls did not reach the lower range value of patients.

Autoantibodies↗

An open and flexible framework for computer aided surgical training.

During the past year we have developed a new surgical skills training application called LapSim. We intend to describe the design, architecture and concepts of the software framework we have developed concurrently with the application. The framework is based on the concept of a classroom with students and teachers. Students, courses and results are stored in a centralized database and can be retrieved for review or modification. The students can also monitor their progress relative to other students or experts.

Computer Systems↗

Intracorporeal suturing and knot tying in surgical simulation.

Intracorporeal suturing and knot tying is one of the most difficult tasks to perform during minimally invasive surgery. To master these tasks the student requires extensive training in a real or simulated environment. Realistic simulation of suturing and knot tying is a challenging task, the dynamic behaviors of the needle and thread are complicated to calculate efficiently in real time. We present our approach to simulated training of intracorporeal suturing and knot tying as well as our method for performance assessment. Different algorithms for physical modeling of suture thread dynamics are examined and evaluated.

Computer Simulation↗

Immobilization of trypsin on porous glycidyl methacrylate beads: effects of polymer hydrophilization.

The immobilization of trypsin at porous glycidyl methacrylate (GMA-GDMA) beads was investigated. In particular, the effects of surface modification of the beads through hydrophilic polymers on the amount protein immobilized and on the extent of retained activity after immobilization were adressed. Furthermore, immobilization at unmodified and hydrophilized beads from aqueous solution was compared to that from a water-in-oil microemulsion. It was found that the amount trypsin immobilized at the unmodified GMA-GDMA beads was significantly higher than that at hydrophilized GMA-GDMA beads. However, also the extent of specific activity loss after immobilization was larger for the unmodified than for the hydrophilized beads. Despite the latter, however, the total activity displayed by the hydrophilized beads was comparable to the unmodified beads at best. On the other hand, by peforming the immobilization from the microemulsion a high immobilization yield can be reached even for the hydrophilized beads, which also results in a higher degree of retained activity in the latter case than obtained for immobilization at the unmodified beads. Using this approach therefore resulted in the highest total activity of the trypsin-activated GMA-GDMA beads.

Journal Article↗

[Wide variations among hospitals in use of laboratory tests. Information and education to increase cost-effectiveness].

Hospitals in Sweden differ greatly in their use of laboratory tests. These differences seem to be due to traditions and regional differences. The cost of a single laboratory test is often low, but since many tests are used in great numbers, the consequences of false or misleading results can be very costly. Recently, several intervention studies have been carried out in Sweden with the aim of optimizing clinical chemistry testing routines in primary care. These studies show that it is possible to reduce the cost to primary care by SEK 100 million per year while increasing clinical utility. SEK 100 million is approximately 10% of the total cost of clinical chemistry testing in primary care. It should also be possible to reduce this cost in secondary and tertiary care. Hospitals order more tests than primary care, and thus the potential savings are larger. We have studied ordering routines at eleven Swedish hospitals. Comparisons were made in the form of ratios between related laboratory tests, in order to reduce the effects of differences of scale between the laboratories that were studied. The large variation between hospitals indicates that an ongoing discussion between clinicians and laboratories could reduce costs. We have used the figures from this comparison and calculated the potential savings for seven frequently used tests. The potential yearly savings in Sweden for these tests alone is approximately SEK 150 million. We estimate that this is just half of the amount that could be saved if all tests were included.

Chemistry, Clinical↗