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R S Heyderman

Publications and source records attributed to R S Heyderman.

48 records · Page 3Linked to original sources
PubMed1992

Reduction of the anticoagulant activity of glycosaminoglycans on the surface of the vascular endothelium by endotoxin and neutrophils: evaluation by an amidolytic assay.

The processes that underlie the coagulopathy observed in severe infection are not fully understood, but seem to be due to an imbalance in the antithrombotic, and prothrombotic properties of the vascular endothelium. Sulphated glycosaminoglycans (GAGs) present on the vessel wall represent an important component of the non-thrombogenic nature of the endothelium. We have modified an amidolytic assay to study the functional ability of GAGs on human umbilical vein endothelial cells (HUVECS), and investigate the effect of E. coli endotoxin and neutrophils on HUVEC surface anticoagulant activity (SAA). Neither endotoxin alone, nor separated neutrophils at lower concentrations (less than 10(6) neutrophils per ml), had major effects on endothelial SAA. When activated neutrophils were incubated with HUVECS pre-stimulated with endotoxin, a significant decrease in SAA was seen using either plasma (mean percentage of control 67.8% +/- sem 7.8; p < 0.02) or purified ATIII (mean percentage of control 69% +/- sem 4.6; p < 0.001). We suggest that alterations in endothelial surface GAGs may occur during sepsis and inflammation, and that this may have important consequences for vascular function. This system will allow the further study of the role of GAGs in the intravascular thrombosis of severe sepsis, and other inflammatory diseases.

Anticoagulants↗
PubMed1992

Does computed tomography have a role in the evaluation of complicated acute bacterial meningitis in childhood?

The authors examined the records of 30 children with bacterial meningitis to review the role of computed tomography (CT) of the brain in acute management of the disease. CT was normal for 10 patients, six of whom had clinical evidence of raised ICP. CT identified an underlying surgical abnormality in two patients with progressive focal neurological signs. One patient had unsuspected gross hydrocephalus diagnosed by CT, which required neurosurgery. This study shows that the management of bacterial meningitis is influenced by CT in only a minority of cases; for patients with clinical signs of raised ICP, it was found to be insensitive in confirming the clinical diagnosis and establishing an underlying cause. However, CT remains valuable in the management of children with progressive neurological signs for whom neurosurgical intervention may be necessary.

Acute Disease↗
PubMed1992

Alteration in glycosaminoglycan metabolism and surface charge on human umbilical vein endothelial cells induced by cytokines, endotoxin and neutrophils.

There is increasing evidence that the glycosaminoglycan (GAG) component of the vascular endothelium is important in regulating vascular permeability, thromboresistance and cellular interactions. We have investigated the GAG metabolism of cultured human umbilical vein endothelial cells (HUVEC) in response to a range of inflammatory stimuli. Using both chemical measurement of cellular and supernatant GAGS and 35S labelling to identify newly synthesised GAGS, interleukin 1 (IL1), tumour necrosis factor (TNF) and interferon gamma (IFN gamma) were shown to influence sulphated GAG metabolism significantly. IL1 and TNF caused a marked increase in culture supernatant GAGS and a concomitant reduction in cell-associated GAGS. This was shown histochemically to be associated with a marked reduction and redistribution of endothelial surface anionic sites. The addition of neutrophils to HUVEC pretreated with Escherichia coli endotoxin, IL1 or TNF resulted in a further reduction in both cellular GAGS and surface anionic sites. These results suggest that changes in endothelial cell GAG metabolism during inflammation may contribute to the disturbance of vascular endothelial homeostasis associated with infectious and inflammatory states.

Adult↗
PubMed1991

Successful bone marrow transplantation and treatment of BCG infection in two patients with severe combined immunodeficiency.

We report successful bone marrow transplantation (BMT) in two patients with severe combined immunodeficiency (SCID), who had developed BCG infection following neonatal vaccination. Patient 1 had Omenn Syndrome, associated with hypertrophic non-obstructive cardiomyopathy. Patient 2 had SCID due to adenosine deaminase deficiency. This communication demonstrates that with appropriate anti-mycobacterial cover, immunological reconstitution together with full recovery from BCG infection can be achieved by BMT. As demonstrated by persistent negative Mantoux tests, specific cell-mediated immunity to BCG was not acquired following BMT. We suggest that these children may continue to be at risk from mycobacterial infection.

Adenosine Deaminase↗
PubMed1991

Deficiency of prostacyclin production in meningococcal shock.

A deficiency of prostacyclin (PGI2) production by the vascular endothelium might underline the severe vasoconstriction and intravascular thrombosis that characterise meningococcal shock. The effect on PGI2 synthesis by human umbilical vein endothelial cells (HUVEC) in culture was examined in sera from children with meningococcal shock, healthy adults, and children with other febrile illnesses. In comparison with adult controls, PGI2 synthesis was reduced when HUVEC were incubated with the sera from 10 of 13 patients with meningococcal shock. A similar defect was observed with only four of 20 sera from children with other febrile illnesses. The effect of sera from patients with meningococcal shock on HUVEC was reversible with normal serum, and seems to be due to the absence of a factor necessary for PGI2 production rather than an inhibitor. These findings suggest that a deficiency of PGI2 may have a role in the pathogenesis of meningococcal shock and that exogenous PGI2 may be of therapeutic benefit.

Adult↗
PubMedDate not supplied

Management of meningococcal infections.

The last 5 years has seen an increase in the number of cases of meningococcal infection. Despite the availability of highly active antibiotics, the mortality from this infection remains at 10%, rising to 40% in patients presenting in severe shock. Here we describe the spectrum and pathophysiology of meningococcal infections, and the most important aspects of treatment and management.

Bacteremia↗