Regulation of streptokinase-human plasmin complex by the plasma proteinase inhibitors alpha 2-antiplasmin and alpha 2-macroglobulin is species specific and temperature dependent

Streptokinase-plasmin complex (SkPl) was prepared with human plasminogen. Regulation of SkPl and plasmin by the plasma proteinase inhibitors, alpha 2-antiplasmin (alpha 2AP) and alpha 2-macroglobulin (alpha 2M), was studied as a function of temperature in plasminogen- depleted human plasma, mouse plasma, and solutions of purified proteins. The reaction of plasmin with proteinase inhibitors in human plasma was complete. alpha 2AP was the predominant inhibitor. The fraction of alpha 2M-plasmin recovered was not affected significantly by incubation temperature. In contrast, the reaction of SkPl with human proteinase inhibitors was markedly temperature dependent. The apparent second-order rate constant for the reaction of SkPl with purified alpha 2AP at 37 degrees C (1.5 x 10(2) mol/L-1 s-1) was greater than 150-fold higher than the constant derived at 4 degrees C. In human plasma and in solutions containing mixtures of purified human proteins, alpha 2AP was the principal inhibitor of SkPl. Elevating the temperature enhanced the reaction of SkPl with alpha 2AP and alpha 2M comparably. Equivalent results were obtained when incubations were performed in platelet-rich plasma (PRP) or whole blood. In murine plasma, SkPl reacted readily with the proteinase inhibitors. The principal inhibitor of SkPl was alpha 2M. Maximum reaction between SkPl and murine alpha 2M was observed at 37 degrees C; however, significant reaction also occurred at 4 degrees C. alpha 2 AP was the predominant inhibitor of plasmin in mouse plasma. Reaction of alpha 2AP with SkPl in murine plasma was significant only after the alpha 2M was inactivated with methylamine. These results were not affected by platelets or whole blood cells. We conclude that the thrombolytic efficacy of streptokinase reflects not only the nature of the plasminogen activator complex but also the function of the proteinase inhibitors.     

Malignant fibrous histiocytomas of salivary glands

The light microscopic, immunohistological and ultrastructural findings in two cases of malignant fibrous histiocytoma arising in salivary glands are presented and the features of seven previously reported cases are reviewed. This neoplasm is extremely rare in this site and may pose problems in diagnosis. It has to be distinguished from other spindled cell tumours, in particular from epithelial tumours of predominantly spindled cell pattern; immunohistological markers for histiocytic cells may be of value. The histogenesis of this neoplasm is controversial but our electron microscopic findings support an origin from mesenchymal cells which differentiate along a broad fibrohistiocytic spectrum.     

A Review of Interspecies Toxicity Extrapolation in Birds and Mammals and a Proposal for Long-term Toxicity Data

Terrestrial risk assessments for pesticide exposure is generally based on a limited number of toxicity data. The protection target for these assessments requires an extrapolation from species for which toxicity data are available to other species with unknown sensitivity to be able to protect these as well. Our ability to extrapolate toxicity endpoints between species is a major source of uncertainty in risk assessment. Most analyses of interspecies extrapolation in avian risk assessments have dealt with acute toxicity data. It was suggested that, in the absence of a strong rationale to the contrary, we should assume that reproductive data is at least as variable as acute data and that strategies developed for acute data could be applied to long term toxicity data as well. Considering only the two main bird test species for which reproduction data are available (Mallard and Northern Bobwhite), a comparison of the interspecies standard deviation for both acute and reproduction data suggests that the two are equally variable. Analysis of a very limited data set also suggests that this conclusion holds regardless of which endpoint is triggered in the reproduction study. However, the relative sensitivity of the two species established from acute test data appears to be reversed in the case of reproductive data. In addition there seems to be no reason to believe that bodyweight is a factor in helping birds cope with the rigours of chronic dosing, which is in contrast with the acute dosing situation. This suggests that the best extrapolation technique for reproduction test data should be independent of phylogeny and independent of bodyweight scaling. The simplest such method is the one that was proposed by Luttik and Aldenberg (1995, 1997) for both birds and mammals.     

Appendiceal intussusception mistaken for a polyp at colonoscopy: case report and review of literature

We report a case of appendiceal intussusception which was erroneously labelled as a 10-mm polypoid caecal lesion on colonoscopy and, therefore, followed up over an 11-year period before the correct diagnosis was made. We present the radiological and endoscopic appearance of appendiceal intussusception and a review of the literature.     

Early high C-reactive protein in infants with open abdominal wall defects does not predict sepsis or adverse outcome

Aim:  To study CRP values and relate it to outcome in infants with antenatal diagnosis of gastroschisis, exomphalos and other surgical conditions.
Methods:  Over five years, infants admitted to our neonatal unit with gastroschisis, exomphalos and other surgical diagnoses were identified. Serum CRP measurements in first 5 days were studied. Group one included 33 gastroschisis patients, group two, 18 exomphalos patients, and group three, 38 patients with other surgical diagnoses. Outcome measures included TPN days, time to full feeds and duration of hospitalization.
Results:  Infants with gastroschisis were more premature (36.9 vs 38.1 weeks) with lower birth weights (2515 vs 3078 g), than infants with exomphalos. CRP values on admission in gastroschisis group were significantly higher than exomphalos and other diagnoses groups (33.7 ± 6.4 vs 8.8 ± 6.0 vs 5.7 ± 2.0, respectively, p   <   0.05). All blood cultures were sterile. There was no relationship between high CRP and death or adverse outcome (TPN days, time to full feeds or duration of hospitalization) in the gastroschisis group.
Conclusion:  Infants with gastroschisis exhibit high early CRP, which may not indicate sepsis or adverse outcome. This increase can complicate the assessment of these infants. Clinicians should be aware of this finding as it could inform management decisions in this group.     

The effectiveness of a training for patients with unexplained physical symptoms: protocol of a cognitive behavioral group training and randomized controlled trial

Background  

In primary care, up to 74% of physical symptoms is classified as unexplained. These symptoms can cause high levels of distress and healthcare utilization. Cognitive behavioral therapy has shown to be effective, but does not seem to be attractive to patients. An exception herein is a therapy based on the consequences model, which distinguishes itself by its labeling of psychosocial distress in terms of consequences rather than as causes of physical symptoms. In secondary care, 81% of the patients accepts this therapy, but in primary care the outcome is poor. We assume that positive outcome can also be reached in primary care, when the consequences model is modified and used bottom-up in an easily accessible group training, in which patients are relieved of being blamed for their symptoms. Our aim is to investigate the (cost-)effectiveness of this training.