Persistence of varicella-zoster virus viraemia in patients with herpes zoster.

BACKGROUND: Herpes zoster is caused by the reactivation of varicella-zoster virus from sensory neurons. The commonest complication following zoster is chronic pain termed post herpetic neuralgia. OBJECTIVES: To investigate the dynamics of VZV viraemia and viral load following the resolution of zoster and its relationship to PHN development. STUDY DESIGN: Blood samples were collected at baseline, 1 month, 3 months and 6 month from a prospective study of 63 patients with active zoster. Quantification of VZV DNA in whole blood was performed using a real-time PCR assay. RESULTS: During acute zoster, all patients had detectable VZV DNA in their blood. VZV DNA remained detectable in the blood of 91% of patients at 6 months although levels declined significantly (p<0.0001). A history of prodromal symptoms (p=0.005) and severity of pain at baseline (p=0.038) as well as taking antivirals (p=0.046) and being immunocompromised (p=0.043) were associated, with longer time to recovery from PHN. Viral DNA loads were consistently higher in patients with risk factors for PHN and higher viral DNA loads over time were associated with longer time to recovery (p=0.058 overall and 0.038 in immunocompetent). CONCLUSIONS: Based on these observations we hypothesise that VZV replication persists following acute shingles and that higher viral DNA loads contribute to the risk factors for PHN.

The beneficial effects of omega-3 and omega-6 essential fatty acid supplementation on red blood cell rheology.

Twenty healthy, non-smoking subjects were enrolled into a study to investigate the effects of dietary supplementation with essential fatty acid (EFAs) on red blood cell rheology. Ten subjects were given 3 months dietary supplementation with long chain polyunsaturated EFAs containing omega-3 and omega-6 EFAs while 10 others were given placebo (sunflower oil). Venous sampling was performed at 0 and 12 weeks and red blood cell (RBC) aggregation and deformability measured by a filtration system. The results showed a reduction in RBC aggregation in the group given omega-3 and omega-6 EFAs but not in the placebo group. This may be related to changes in the RBC membrane and surface receptor characteristics. Such EFAs may be useful in Raynaud's phenomenon.

Soluble cell adhesion molecules--P-selectin and ICAM-1, and disease activity in patients receiving sulphasalazine for active rheumatoid arthritis.

The aim of this pilot study was to examine soluble cell adhesion molecules before and after sulphasalazine (SSZ) therapy in active RA. Assessment of RA patients (n = 13) was undertaken before and after 3 months of SSZ. sICAM-1, sVCAM-1, sP- and sE-selectin were measured using an ELISA. The mean (+/-SEM) C-reactive protein (CRP) and sP-selectin levels were significantly reduced from 3.9(0.89) to 2.01(0.53) mg/dl and from 332.8 (48.2) to 116.2 (11.1) respectively, after 3 months of SSZ. The sICAM-1 and sP-selectin levels were significantly higher in RA patients at baseline and a reduction occurred of sICAM-1, sVCAM-1 and sE-selectin levels, however this was not significant. The fall in mean (SEM) sICAM-1, from 345.0 (29.8) to 333.5 (30.2), correlated with the change in CRP (r=0.66; p = 0.018), but the fall in sP-selectin did not. SSZ therapy reduced sP-selectin and sICAM-1 levels in active RA, sICAM-1 correlates with disease activity. SSZ may reduce platelet and/or endothelial activity in RA which may be a useful marker of response, however studies of longer duration and more patients are required.

Dietary supplementation with omega 3 and omega 6 fatty acids reduces induced white blood cell aggregation in healthy volunteers.

Twenty healthy, non-smoking subjects were enrolled into a study to look at the effects of 3 months' dietary supplementation with long chain polyunsaturated essential fatty acids (EFAs) on white blood cell (WBC) aggregation. Ten subjects received 3 months' supplementation with long chain polyunsaturated omega 3 and omega 6 fatty acids, 10 received 3 months of placebo (sunflower oil). Venous blood was sampled at 0 and 12 weeks; whole blood WBC aggregation in response to formyl-methionyl-leucyl-phenylalanine (FMLP) was measured. The results showed that the 3 months' dietary supplementation with a combination of omega 3 and omega 6 fatty acids significantly reduced WBC aggregation to FMLP in healthy volunteers when compared to placebo. Since WBC aggregation to FMLP is dependent on the activity of WBC surface receptors and independent of eicosanoid production, we suggest EFAs may have other anti-inflammatory actions in addition to their role as modulators of mediator production.

A circadian variation exists for soluble levels of intercellular adhesion molecule-1 and E-selectin in healthy volunteers.

1. We have previously shown a circadian variation in leucocyte activation and endothelial function which may explain why some inflammatory and vascular diseases show a circadian variation in disease activity/ occurrence. 2. We have investigated the circadian variation of two soluble cell adhesion molecules, intercellular adhesion molecule-1 and E-selectin, in 10 healthy volunteers. Soluble intercellular adhesion molecule-1 is released from both activated leucocytes and endothelial cells while soluble E-selectin is released only from activated endothelium. 3. Results show a circadian variation exists for both soluble intercellular adhesion molecule-1 and E-selectin (both P < 0.0001, analysis of variance) with a peak activity at 12:00 h for both measures and a minimum activity at 04:00 h for intercellular adhesion molecule-1 and 00:00 h for E-selectin. 4. These results demonstrate the existence of a diurnal variation in cell adhesion molecules, providing evidence in support of a diurnal pattern in endothelial and leucocyte activation. An alteration in this biological rhythm may help to explain the diurnal variation in disease activity in certain inflammatory and vascular disease states. Furthermore, it stresses the importance of sample time point standardization in clinical studies.

The white blood cell adhesion molecule E-selectin predicts restenosis in patients with intermittent claudication undergoing percutaneous transluminal angioplasty.

BACKGROUND: Experimental studies have shown that endothelial dysfunction is an early event preceding restenosis. Monocytes and neutrophils have been shown to bind to damaged endothelium via the cell adhesion molecules (CAMs). The selectins are involved in capturing the leukocytes and tethering them to the endothelium. E-selectin is a CAM that is only expressed on activated endothelial cells. Its ligands are expressed on monocytes and neutrophils and it has been found to exist in a soluble form. This soluble form may represent a marker for endothelial damage and may be a precursor of smooth muscle proliferation. METHODS AND RESULTS: Fifty-four patients who were undergoing peripheral arterial balloon angioplasty had blood sampled before angioplasty. E-selectin was measured in plasma with the use of an ELISA. At follow-up angiogram, 30% (n=14) of the patients had restenosed at 1 year. There was a significant difference in baseline E-selectin levels in patients who restenosed compared with those who did not (65.3 ng/mL [58.25 to 78.05] versus 52.3 [34.2 to 62.1], Mann-Whitney U, P<.007). Endothelial activation with subsequent adherence of white blood cells is an important step in restenosis. CONCLUSIONS: We have shown an increased level of shed E-selectin in patients destined for restenosis and suggest that this work further supports a role for white blood cell/endothelial interaction in restenosis after angioplasty.

Cell adhesion molecules in rheumatoid arthritis.

Rheumatoid arthritis is a systemic inflammatory disease of the joints and major internal organs that has an unknown aetiology. Cell adhesion molecules (CAMs) are expressed on the surface of cells, enabling homotypic and heterotypic cell-cell interactions that are fundamental in the process of the inflammatory reaction. Three major families of CAMs are now recognised, with numerous subtypes. Many of these molecules play an important role in the mechanism of disease in rheumatoid arthritis. E-Selectin and intercellular adhesion molecule (ICAM)-1 are upregulated on the synovial endothelium, while vascular cell adhesion molecule (VCAM)-1 plays an important role in the synovial lining layer cells and within the synovial stroma. The expression of CAMs may be blocked by monoclonal antibodies and modified by nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs. This has very important implications in the therapy of rheumatoid arthritis.

Transmission of hepatitis C virus by organ transplantation in the United Kingdom.

This study employed a second-generation anti-HCV ELISA, and a second-generation recombinant immunoblot assay and hepatitis C virus RNA detection by polymerase chain reaction to investigate the anti-HCV prevalence in 554 British organ donors and the transmission of hepatitis C virus to heart, liver and kidney recipients between 1984 and 1991. Serum samples from six (1.08%) donors were reactive in the second-generation anti-HCV ELISA and four (67%) of these gave positive or indeterminate results in the recombinant immunoblot assay-2. Of the 15 recipients of these organs from hepatitis C virus-confirmed positive/indeterminate donors, 14 (93%) acquired hepatitis C virus infection and seven (47%) had evidence of hepatitis C virus-related liver disease after transplantation and no evidence of blood transfusion-related transmission. Only six of the 15 (40%) recipients had detectable anti-HCV after transplantation, while 12 of 14 (86%) patients tested had hepatitis C virus RNA in their serum detectable by "nested" polymerase chain reaction. These data indicate a very high rate of transmission with a major risk of the development of liver disease. We believe our study supports the testing of all British organ donors for anti-HCV and that organs from anti-HCV-positive patients should not be transplanted unless the recipient has life-threatening disease and there is a donor shortage, when their use may be justified. Since there are time constraints on organ donor testing, which may frequently be done on call during unsocial hours, we would recommend second-generation ELISA as the current screening test of choice.(ABSTRACT TRUNCATED AT 250 WORDS)