Torstein Lyberg

Toxic effects of methylmethacrylate monomer on leukocytes and endothelial cells in vitro

The influence of methylmethacrylate monomer (MMA) on the cellular integrity of monocytes, granulocytes and endothelial cells in vitro was investigated. Clinically relevant blood concentrations of MMA (i.e., 5-10 micrograms/mL) were clearly cytotoxic to all cell types studied, as evidenced by the release of lactic dehydrogenase (LD) and 51Cr, and increased uptake of trypan blue (vital staining). Scanning electron microscopic examination of cells treated with 10 micrograms/mL MMA showed marked signs of cytotoxicity after 1 min incubation, and after 30 min the majority of the cells were totally disintegrated. These findings may have clinical bearing on intraoperative cardiorespiratory dysfunction and deep vein thrombosis in MMA-fixed joint replacement surgery.

Cellular cooperation in endothelial cell thromboplastin synthesis

Summary. Endothelial cells from human umbilical veins produce a procoagulant identified as thromboplastin (tissue factor, factor III) when stimulated with the phorbol ester 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA), phytohaemagglutinin (PHA) or endotoxin. Inducible thromboplastin synthesis (i.e. synthesis of the protein component of thromboplastin, apoprotein III) was totally inhibited by cycloheximide and actinomycin D, indicating that de novo protein and RNA syntheses are necessary. Serum enhanced the induced apoprotein synthesis.

Increased cardiac IL-18 mRNA, pro-IL-18 and plasma IL-18 after myocardial infarction in the mouse; a potential role in cardiac dysfunction

OBJECTIVE Interleukin (IL)-18 has been reported to be an important predictor for mortality in ischemic heart disease. IL-18 has proinflammatory properties, induces cell death and stimulates nitric oxide production. We hypothesized that following myocardial infarction (MI) an increased myocardial IL-18 production occurs, which may be involved in the pathogenesis of post-ischemic heart failure. METHODS AND RESULTS Seven days after induction of MI in the mouse, myocardial hypertrophy and pulmonary edema were observed. RNase protection assay of tissue from the non-infarcted left ventricular myocardium revealed an increase in IL-18 (2.0-fold; P<0.001) and IL-1 beta (1.6-fold; P<0.001) mRNA after MI. Enhanced abundance of pro-IL-18 (1.4-fold; P<0.05), IL-18 receptor (3.5-fold; P<0.05) and IL-18 binding proteins (1.6-fold; P<0.05) was also demonstrated, whereas cardiac IL-18 protein decreased by 25% (P<0.05) following MI. However, the concentration of circulating IL-18 was significantly elevated (MI; 90.4+/-11.7 pg/ml, sham; 47.2+/-4.2 pg/ml; P<0.001). After MI, enhanced cardiac activity of the pro-IL-18 processing enzyme, caspase-1, was measured. Additionally, a 3.4-fold increase (P<0.001) in the activity of the IL-18 degrading enzyme, caspase-3, was found in cardiac tissue, which may explain the observed reduction of cardiac IL-18 protein abundance. Finally, IL-18 reduced shortening of electrically stimulated adult cardiomyocytes and left ventricular contractility in vivo. CONCLUSIONS After MI in the mouse, increased production of cardiac IL-18 mRNA and pro-IL-18, as well as circulating IL-18 occurs. Since IL-18 also reduced myocardial contractility, we suggest that IL-18 may be involved in the pathogenesis of contractile dysfunction following MI.

Apheresis-induced platelet activation:comparison of three types of cell separators

BACKGROUND: Platelet‐harvesting technology differs in various cell separators. Alteration in shear stress and biocompatibility of surfaces may give variable platelet activation and thereby affect the quality of the component.

Blood platelet activation evaluated by flow cytometry: optimised methods for clinical studies

A variety of flow cytometry techniques are in use to evaluate in vivo blood platelet activation. We have in this study further developed and optimised these methods to be suitable for use in clinical studies. By preloading the Monovette® EDTA vacuum blood sampling tubes with 1/8 vol 4% (w/v) paraformaldehyde (PFA), we were able to assess platelet CD62P (P-selectin) expression in whole blood with less than 0.2% activated platelets. No washing or neutralising steps were required to remove excess fixative. Both basal and agonist-stimulated CD62P expression were stable for at least 48 h after sampling. The standard curve was linear from 1.9 (basal) to 8.1·10 3 (TRAP-stimulated) molecules of equivalent soluble fluorochrome units (MESF) in phycoerythrein-conjugated anti-CD62P labelled whole blood samples. These assay conditions were also well suited for assessment of platelet expression of CD41, CD42a, CD61 and CD63. The preanalytic storage period was extended from 10 min to at least 2 h for platelet PAC–1 and fibrinogen binding analysis by preloading Monovette® citrate tubes with 8/10 vol buffer. With PFA preloading, blood sampled into citrated tubes could be analysed for fractions of microparticles and platelet–platelet aggregates as well as for aggregate size.

Increased activation of coagulation and formation of late deep venous thrombosis following discontinuation of thromboprophylaxis after hip replacement surgery

Hip replacement surgery (HRS) is associated with a high frequency of deep vein thrombosis (DVT). At the same time there is a substantial systemic and local activation of coagulation. This study indicates that discontinuation of thromboprophylaxis one week after surgery may allow a second wave of coagulation and fibrinolysis activation to occur. An almost parallel increase in plasma TAT and D-dimer levels between the 6th and the 35th postoperative day may indicate late DVT formation. Repeated bilateral ascending venography is though to be necessary to evaluate the suitability of using selected activation markers of the coagulation and fibrinolytic systems as indices of DVT formation.

Surgical treatment of internal derangement of the temporomandibular joint: Long-term evaluation of three techniques☆

PURPOSE The long-term outcomes of three different surgical treatments for internal derangement of the temporomandibular joint (TMJ), ie, discoplasty, discectomy without replacement, and discectomy with replacement of the disc with a Proplast-Teflon (Vitek Inc, Houston, TX) interpositional implant (PTIPI) are compared. MATERIALS AND METHODS Forty-two cases of internal derangement of the TMJ were treated with disc repair and eminectomy (group A, n = 13), simple discectomy (group B, n = 17) and discectomy combined with insertion of a PTIPI (group C, n = 12). Preoperative and postoperative findings (more than 5-year follow-up) relating to pain, mouth opening, joint noise, and radiographic changes were compared. RESULTS Decrease of symptoms after surgery was reported by 77%, 94%, and 83% of the patients (groups A, B, and C, respectively). The decrease in pain intensity ranged from 52% to 71%. Mouth opening increased in 50% to 60% of the patients. The percentage increase ranged from 15% to 26% in the respective groups. Development of osteoarthrosis after surgery was demonstrated in 93% and 100% of the cases in the discectomy and discectomy/disc implant group, respectively, but only in 62% of the discoplasty group. CONCLUSION This study demonstrates the importance of a functioning disc in the TMJ. There was no significant difference between the groups concerning symptoms before and after surgery. The discoplasty group, however, showed a high frequency of relapse, which necessitated secondary discectomy. PTIPIs clearly accelerated the development of osteoarthrosis, which may be classified as iatrogenic damage. The need for further research to establish the long-term performance of autogenous grafts and the development of improved alloplastic disc replacement materials is discussed.

Sequential intrapulmonary and systemic activation of coagulation and fibrinolysis during and after total hip replacement surgery

Hip joint replacement surgery, using acrylic cement for prosthesis fixation, is associated with intraoperative cardiorespiratory dysfunction, and a high frequency of postoperative proximal deep vein thrombosis (DVT). Levels of prothrombin fragments 1+2 (F1+2), tissue plasminogen activator antigen (t-PA), plasminogen activator inhibitor 1 activity (PAI-1), D-dimer and interleukin 6 (IL-6) were measured in arterial (AB) and mixed venous blood (MVB) in five patients during and after total hip replacement operation with acrylic cement prosthesis fixation. Sequential peaks of F1+2, t-PA, PAI-1 and IL-6 appeared, starting with activation of coagulation during preparation of bone, closely followed by activation of fibrinolysis. Later, this was counteracted by an antifibrinolytic response and increase of IL-6. After a fibrinolytic shutdown on the third postoperative day as evidenced by a drop in t-PA and D-dimer concentrations, a second wave of coagulation was seen at the end of the first week. The present model, with frequent sampling of blood entering and leaving the lungs, confirms our earlier findings of the lung as a key organ in promoting coagulation following traumatic activation.

Factors influencing the predictability of soft tissue profile changes following mandibular setback surgery.

The objective of this cephalometric study was to assess long-term changes in the soft tissue profile following mandibular setback surgery and investigate the presence of factors that may influence the soft tissue response to skeletal repositioning. The subjects enrolled were 80 consecutive mandibular prognathism patients operated with bilateral sagittal split osteotomy and rigid fixation. Lateral cephalograms were taken at 6 occasions: immediate presurgical, immediate postsurgical, 2 and 6 months postsurgical, and 1 and 3 years postsurgical. The subjects were grouped according to gender and magnitude of setback. Ratios of soft tissue to hard tissue movements were calculated for the subgroups. Females generally demonstrated greater ratios than males with a statistically significant difference for the upper lip and chin (P < .05). Postsurgical alterations in the profiles were more predictable in patients with larger setbacks compared to patients with smaller ones. Skeletal relapse had a profound influence on long-term profile changes. Based on these findings, it is proposed that the database used in prediction software be adjusted to account for such factors in an attempt to improve the accuracy of computerized treatment simulations.

Effects of the Medicinal Mushroom Agaricus blazei Murill on Immunity, Infection and Cancer

Agaricus blazei Murill (AbM) is an edible, medicinal mushroom of Brazilian origin. It is used traditionally against a range of diseases, including cancer and chronic hepatitis, and has been cultivated commercially for the health food market. AbM has recently been shown to have strong immunomodulating properties, which has led to increasing scientific interest. In this article, we review current knowledge as to the immunological properties of AbM, and its possible clinical use in connection with infections and cancer. We also present some novel findings, which point to highly different biological potency between AbM extracts of different source and manufacturing.