Prospective study on soluble thrombomodulin and von Willebrand factor and the risk of ischemic and hemorrhagic stroke

The aim of the present study was to examine if soluble thrombomodulin (sTM) and von Willebrand factor (VWF) could predict a first-ever ischemic or hemorrhagic stroke. This study was an incident case-referent study from within a population-based cohort in northern Sweden. Up to 1996 about 44,000 subjects had been screened and stroke cases were classified according to the WHO MONICA criteria. A first-ever stroke occurred in 108 cases. A total of 216 controls were selected from the same cohort. This prospective study found no association with sTM or VWF and the development of a first-ever ischemic stroke (n = 87) in the logistic regression model. For the hemorrhagic stroke cases (n = 18), the multivariate logistic regression model revealed a significant negative association with sTM. When dichotomized, the upper level (>17.3 microg/L) of sTM, as compared with the lower level (<17.3 microg/L), showed one fifth of the risk for hemorrhagic stroke (OR, 0.18; CI, 0.05 to 0.69). No significant association was found for VWF. We suggest that the novel finding of an inverse relation between sTM and hemorrhagic stroke should be investigated in a larger study.     

Wegener granulomatosis in children and young adults

This retrospective study reports seven children and three young adults (aged 11–30 years) who suffered from Wegener granulomatosis. Nine represent consecutive patients admitted to the Division of Nephrology over a period of 23 years. All patients had respiratory tract symptoms and renal involvement on admission. In several patients infiltrates on chest X-ray developed within 2 weeks of onset of symptoms. All patients survived. The median observation period was 9 years (range 13 months to 23 years). One patient progressed to end-stage renal disease. Nine patients initially received cyclophosphamide and steroids. After a median period of 9 months (range 6–31 months) the cyclophosphamide was replaced by azathioprine. Relapses occurred after a median of 28 months (range 4–120 months) in 80% of patients, in six of the eight patients causing a definite decrease in kidney function. We believe that early diagnosis and initiation of therapy reduce the extent of organ damage. Since relapses are frequent, these patients should be evaluated frequently. Received: 18 December 1997 / Revised: 1 December 1998 / Accepted: 2 December 1998     

Comprehensive medical examination of a group of patients with alleged adverse effects from dental amalgams.

Mercury from dental amalgams does not seem to cause dose-related intoxications. However, animal studies have shown that high-dose exposure to mercury may support various types of immunologic reactions. Ten patients claiming that their symptoms were caused and aggravated by amalgam therapy were selected for a study of the effects of removal of one amalgam restoration followed by placing of a composite filling. Clinical symptoms and the result of laboratory tests were recorded. Six patients had contact allergies to metals, three of them to mercury ammonium chloride. The comparison of pre- and post-experimental test results showed significant reductions in p-IgE and dU-albumin and significant increases in p-C3d and dU-beta 2-microglobulin. There was no laboratory evidence of a direct toxic effect by mercury on the patients. The observed response by some of the studied factors to the low acute exposure to amalgam may imply that an activation of the immune system occurred.     

Complement activation is influenced by the membrane material, design of the dialyser, sterilizing method, and type of dialysate

The complement system becomes activated during blood-membranecontact in the dialyser. This study was designed to evaluateto what extent the dialyser design, the sterilization method,and the type of dialysate influence complement as measured byC3d. Twelve patients were dialysed three times on each of fourdifferent dialysers. Two hollow-fibre dialysers made of cuprophane(Hf-CuE ethylene-oxidesterilized, Hf-CuS steam-sterilized) werecompared with two plate dialysers made of cuprophane (P-Cu)or polycarbonate (P-Pc). Five patients were dialysed with acetateand seven with bicarbonate. Differences in C3d between at startof dialysis and after 180 mm were calculated. C3d was increasedmore by P-Cu than by the other dialysers (P<0.012, n=12).In the bicarbonate group, C3d was increased more by P-Cu thanby Hf-CuS or P-Pc (P<0.022, n=7) and more by Hf-CuE thanHf-CuS (P<0.013). In the acetate group, C3d was increasedmore by Hf-CuS and P-Cu than by P-Pc (P<0.006, n=5). In conclusion, complement activation during dialysis varieddue to membrane material, membrane design, sterilization method,and dialysate composition.     

A survey of blood purification techniques.

Apheresis may be performed with many different techniques. The basis for different therapeutic approaches lies in the pathophysiological processes present in the diseases that have to be treated. Over the years more sophisticated devices have been developed. The most frequent treatment is plasma exchange (plasmapheresis) using centrifugation or single filtration techniques. In addition cascade filtration and subsequent adsorption from plasma is done. Thereby removal is done by adsorption of molecules such as bilirubin, immunoglobulins (immunoadsorption), circulating immune complexes, various antibodies including those against blood types. Such adsorption technologies have also been developed to allow adsorption directly from a column perfused by whole blood (hemoperfusion). By combining various techniques, systems are available that allow bridging of patients with hepatic failure to transplantation (MARS, Prometheus). By adding e.g., hepatic cells to such systems, besides dialysis and adsorption, cells will help to degrade toxic molecules. Such bioreactors are in clinical use. Apheresis includes also the removal or retrieval of cells from blood for e.g., stemcell transplantation, polycythaemia or hemochromatosis. Removal of leukocytes from blood using leukocyte filters is indicated in inflammatory bowel diseases. By specifically irradiating lymphocytes and monocytes with UV light using the technique of extra corporeal photochemotherapy (ECTP) various immunological diseases are treated. On the other hand, various alternative techniques may be used for the same disorder. Thus for patients with high plasma LDL-cholesterol not responding to other lipid lowering strategic treatment, alternative therapy may be done either by cascade filtration, adsorption technology from plasma, heparin precipitation (HELP-system) or hemoperfusion. This article describes various techniques in clinical use.     

Lipoprotein lipase in hemodialysis patients: indications that low molecular weight heparin depletes functional stores,despite low plasma levels of the enzyme

Background

Lipoprotein lipase (LPL) has a central role in the catabolism of triglyceride-rich lipoproteins. The enzyme is anchored to the vascular endothelium through interaction with heparan sulphate proteoglycans and is displaced from this interaction by heparin. When heparin is infused, there is a peak of LPL activity accompanied by a reduction in triglycerides (TG) during the first hour, followed by a decrease in LPL activity to a stable plateau during the remaining session while TG increase towards and beyond baseline. This suggests that tissue stores of LPL become depleted. It has been argued that low molecular weight (LMW) heparins cause less disturbance of the LPL system than conventional heparin does.

Methods

We have followed LPL activity and TG during a dialysis-session with a LMW heparin (dalteparin) using the same patients and regime as in a previous study with conventional heparin, i.e. a primed infusion.

Results

The shape of the curve for LPL activity resembled that during the earlier dialyses with conventional heparin, but the values were lower during dialysis with dalteparin. The area under the curve for LPL activity during the peak period (0–180 minutes) was only 27% and for the plateau period (180–240 minutes) it was only 36% of that observed with conventional heparin (p < 0.01). These remarkably low plasma LPL activities prompted us to re-analyze LPL activity and to measure LPL mass in frozen samples from our earlier studies. There was excellent correlation between the new and old values which rules out the possibility of assay variations as a confounding factor. TG increased from 2.14 mmol/L before, to 2.59 mmol/L after the dialysis (p < 0.01). From 30 minutes on, the TG values were significantly higher after dalteparin compared to conventional heparin (p < 0.05).

Conclusion

These results indicate that LMW heparins disturb the LPL system as much or more than conventional heparin does.