High-yield preparation of porcine hepatocytes for long survival after transplantation in the spleen

The creation of an auxiliary liver by autotransplantation of liver parenchymal cells into the spleen has mainly been studied in rats for the treatment of acute liver failure. In order to apply this procedure to humans with chronic liver insufficiency the aim of this work was: To demonstrate that hepatocytes can survive for long periods after autotransplantation into the spleen; to increase the yield of the isolation of hepatocytes obtained from pig livers since this animal has a more fibrous liver than rats or normal humans and consequently one which is more difficult to dissociate. In 21 pigs isolated hepatocytes were obtained with in collagenase dissociation technique, the yield being 1-3 X 10(7) cells per gram of liver and the viability 70-95%. The hepatocytes survived and maintained normal morphological and histochemical characteristics up to 7 months after transplantation, the date of sacrifice of the last animal.     

Cemented total hip prosthesis: radiographic and scintigraphic evaluation

Conventional radiographs, technetium-99m bone scans, and gallium-67 scans were reviewed in 44 patients who had undergone cemented total hip joint replacement and were imaged because of suspicion of prosthesis loosening or infection. A complete radiolucent line of 2 mm or wider along the bone-cement interface or metal-cement lucency on conventional radiographs was used as the criterion for prosthetic loosening with or without infection and proved to be 54% sensitive and 96% specific. Scintigraphic criteria for prosthetic loosening were increased focal uptake of the radiopharmaceutical for the femoral component and increased focal or diffuse uptake for the acetabular component. For bone scintigraphy, sensitivity was 73% and specificity was 96%. Combining the results of conventional radiographs and bone scans increased sensitivity to 84% and decreased specificity to 92% for the diagnosis of loosening, infection, or both. The study also showed that Ga-67 scintigraphy has a low sensitivity for the detection of infection.     

Chronic illness and compliance

For a person with a chronic illness, life is altered in some way. Whether simple or complex, changes are nevertheless permanent. A patient with a chronic disease assesses recommended treatments on how well they can be integrated into his life. Evidence suggests that an individual's perception of his situation will determine whether or not he will comply with a medical regimen. Health professionals neglect the patient's point of view if they believe that patients regard the health professional as an absolute authority, thereby contributing to noncompliance. The contingency contract provides a model of patient-provider transaction, which requires input from both parties. The health professional can work with the person to make the medical regimen compatible with the individual's lifestyle.     

The autoimmune lymphoproliferative syndrome: a disorder of programmed cell death

The autoimmune lymphoproliferative syndrome (ALPS) is a chronic, nonmalignant lymphoproliferative disorder caused by mutations in the genes that are involved in programmed cell death (apoptosis). The impaired apoptosis causes accumulation of lymphocytes, which underlies the clinical manifestations of lymphadenopathy, autoimmune phenomena and a markedly increased risk of malignant lymphomas. During the last few decades, great progress has been achieved in elucidating the aetiology of this syndrome. Several mutations have been found in the genes encoding proteins that are involved in the apoptotic cascade, which starts with the binding of the Fas ligand to the transmembranous Fas protein and which is followed by intracellular processes. ALPS is an autosomal dominant hereditary disease with variable penetrance. Unravelling the genetic abnormalities that cause ALPS has provided key insights into the clinical consequences of defective apoptosis.     

Speckle reduction in optical coherence tomography by "path length encoded" angular compounding

Speckle, the dominant factor reducing image quality in optical coherence tomography (OCT), limits the ability to identify cellular structures that are essential for diagnosis of a variety of diseases. We describe a new high-speed method for implementing angular compounding by path length encoding (ACPE) for reducing speckle in OCT images. By averaging images obtained at different incident angles, with each image encoded by path length, ACPE maintains high-speed image acquisition and requires minimal modifications to OCT probe optics. ACPE images obtained from tissue phantoms and human skin in vivo demonstrate a qualitative improvement over traditional OCT and an increased SNR that correlates well with theory.     

Structure-function studies on beta 2-glycoprotein I

Human beta 2-glycoprotein I is a heavily glycosylated plasma protein which has been implicated in the binding of antiphospholipid antibodies to negatively charged phospholipids; a process considered as an important risk factor for the development of thrombosis. We have solved the crystal structure of beta 2-glycoprotein I. In this review we will discuss what the three-dimensional structure teaches us about the role of beta 2-glycoprotein I in the pathogenesis of the antiphospholipid syndrome.     

Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives

The effect of oral contraceptives (OC) on fibrinolytic parameters was investigated in a cycle-controlled cross-over study in which 28 non-OC using women were randomly prescribed either a representative of the so-called second (30 microg ethinylestradiol, 150 microg levonorgestrel) or third generation OC (30 microg ethinylestradiol, 150 microg desogestrel) and who switched OC after a two month wash out period. During the use of OC, the levels of tissue-type plasminogen activator (tPA) activity, plasminogen, plasmin-alpha2-antiplasmin complexes and D-dimer significantly increased (by 30 to 80%), while the levels of plasminogen activator inhibitor- (PAI-1) antigen, PAI-1 activity and tPA antigen significantly decreased (25 to 50%), suggesting an increase in endogenous fibrinolytic activity. These OC-induced changes were not different between the two contraceptive pills. TAFI (thrombin-activatable fibrinolysis inhibitor) levels increased on levonorgestrel, and even further increased on desogestrel. A clot lysis assay that probes both fibrinolytic activity and the efficacy of the coagulation system to generate thrombin necessary to down regulate fibrinolysis via TAFI showed no change of the clot lysis time during OC use. This finding suggests that the OC-induced increase in endogenous fibrinolytic activity is counteracted by an increased capacity of the coagulation system to down regulate fibrinolysis via TAFI. Indeed we observed that during OC use there was a significant increase of F1+2 generation during clot formation. When these assays were performed in the presence of an antibody against factor XI, we observed that the clot lysis time was significantly increased during OC use and that the increase in F1+2 generation during OC therapy was due to a factor XI-independent process, which was significantly higher on desogestrel than on levonorgestrel. These data indicate that the OC-induced inhibition of endogenous fibrinolysis takes place in a factor XI-independent way and is more pronounced on desogestrel than on levonorgestrel-containing OC.