Return-to-work following shoulder arthroplasty in adults with osteoarthritis.

BACKGROUND: Anatomic total shoulder arthroplasty (aTSA) and hemiarthroplasty (HA) have demonstrated significant improvement in shoulder function and pain relief. Work-related outcomes have become increasingly important, while the current literature lacks evidence related to return-to-work (RTW) and which factors might have an influence on it. AIMS: This study aimed to assess RTW in patients who have received aTSA or HA at a minimum of 1-year follow-up after surgery, and secondary to evaluate possible prognostic factors associated with RTW. METHODS: We performed a retrospective query in employed patients diagnosed with primary osteoarthritis of the shoulder, who received either an aTSA or HA between February 2006 and February 2021. Preoperative and post-operative work and sports participation were assessed. RESULTS: Forty-four patients participated in this study (98% compliance), of which 40 patients (91%) were able to RTW at a median time of two (interquartile range: 2-4) months post-operatively. Patients with a medium-/high-demand occupation demonstrated RTW at a significantly lower rate (79%) than those with light-demand occupations (100%; P = 0.03). There was a statistically significant association between return to full employment and patients' expectation to fully return, absence of preoperative work adjustments and preoperative sick leave (odds ratio: 16.9 [3.1-93.5]; 18.3 [2.1-160.4]; 0.1 [0.0-0.6]). CONCLUSIONS: aTSA and HA facilitate excellent RTW rates. Patients with a medium-/high-demand occupation return at a significantly lower rate. The ability to RTW seems to be multifactorial and the results found might not be attributed to shoulder arthroplasty alone.

Systematic review and meta-analysis comparing the autogenous vein bypass versus a prosthetic graft for above-the-knee femoropopliteal bypass surgery in patients with intermittent claudication.

OBJECTIVES: According to guidelines, the autogenous saphenous vein (ASV) is the preferred conduit for femoropopliteal bypass surgery in all patients with peripheral artery disease. However, in contrast to patients with critical limb ischemia (CLI), patients with intermittent claudication (IC) only, tend to have milder disease, and thus a prosthetic graft may be as good as a vein conduit. The objective of this study was to compare patency rates of the ASV and a prosthetic graft in femoropopliteal bypass surgery in patients with IC. METHODS: A systematic literature search was performed in the PubMed, Embase, and Cochrane databases to identify randomized controlled trials comparing prosthetic graft versus ASV in patients with IC. Articles with a mixed IC and CLI study population were included if more than 50% of the study cohort was treated for IC. Primary analysis was performed on IC patients only. Secondary analysis was performed on the mixed group. The primary endpoint was short- and long-term patency and secondary endpoints were complications, limb salvage, and mortality. RESULTS: In total, six studies with 524 patients were included. Only two studies reported solely on patients with IC. All these patients underwent above-the-knee bypasses and average patency rates at one and 5 years were 88% and 76% vs 81% and 68% in the ASV and the PTFE groups, respectively. One and five-year patency was not statistically different between the groups (OR 5.21; 95% CI 0.60-45.36 and OR 2.10; 95% CI 0.88-5.01). In a mixed population of patients with IC and CLI (84% IC patients), 1 year patency was comparable (OR 1.40; 95% CI 0.87-2.25). However, after a follow-up of over 3 years, this mixed group had significantly higher patency rates in favour of the ASV (OR 2.06; 95 % CI 1.30-3.26). Complication and amputation rates were comparable in both groups. CONCLUSIONS: Limited data are available for patients receiving above-the-knee femoropopliteal bypass for intermittent claudication. The ASV remains the conduit of choice for femoropopliteal bypass surgery. However, the prosthetic conduit seems a feasible alternative for patients with intermittent claudication in whom the ASV is not present or unsuitable.

Genome expansion of an obligate parthenogenesis-associated Wolbachia poses an exception to the symbiont reduction model.

BACKGROUND: Theory predicts that dependency within host-endosymbiont interactions results in endosymbiont genome size reduction. Unexpectedly, the largest Wolbachia genome was found in the obligate, parthenogenesis-associated wFol. In this study, we investigate possible processes underlying this genome expansion by comparing a re-annotated wFol genome to other Wolbachia genomes. In addition, we also search for candidate genes related to parthenogenesis induction (PI). RESULTS: Within wFol, we found five phage WO regions representing 25.4% of the complete genome, few pseudogenized genes, and an expansion of DNA-repair genes in comparison to other Wolbachia. These signs of genome conservation were mirrored in the wFol host, the springtail F. candida, which also had an expanded DNA-repair gene family and many horizontally transferred genes. Across all Wolbachia genomes, there was a strong correlation between gene numbers of Wolbachia strains and their hosts. In order to identify genes with a potential link to PI, we assembled the genome of an additional PI strain, wLcla. Comparisons between four PI Wolbachia, including wFol and wLcla, and fourteen non-PI Wolbachia yielded a small set of potential candidate genes for further investigation. CONCLUSIONS: The strong similarities in genome content of wFol and its host, as well as the correlation between host and Wolbachia gene numbers suggest that there may be some form of convergent evolution between endosymbiont and host genomes. If such convergent evolution would be strong enough to overcome the evolutionary forces causing genome reduction, it would enable expanded genomes within long-term obligate endosymbionts.

Tumor-Specific Mitochondrial DNA Variants Are Rarely Detected in Cell-Free DNA.

The use of blood-circulating cell-free DNA (cfDNA) as a "liquid biopsy" in oncology is being explored for its potential as a cancer biomarker. Mitochondria contain their own circular genomic entity (mitochondrial DNA, mtDNA), up to even thousands of copies per cell. The mutation rate of mtDNA is several orders of magnitude higher than that of the nuclear DNA. Tumor-specific variants have been identified in tumors along the entire mtDNA, and their number varies among and within tumors. The high mtDNA copy number per cell and the high mtDNA mutation rate make it worthwhile to explore the potential of tumor-specific cf-mtDNA variants as cancer marker in the blood of cancer patients. We used single-molecule real-time (SMRT) sequencing to profile the entire mtDNA of 19 tissue specimens (primary tumor and/or metastatic sites, and tumor-adjacent normal tissue) and 9 cfDNA samples, originating from 8 cancer patients (5 breast, 3 colon). For each patient, tumor-specific mtDNA variants were detected and traced in cfDNA by SMRT sequencing and/or digital PCR to explore their feasibility as cancer biomarker. As a reference, we measured other blood-circulating biomarkers for these patients, including driver mutations in nuclear-encoded cfDNA and cancer-antigen levels or circulating tumor cells. Four of the 24 (17%) tumor-specific mtDNA variants were detected in cfDNA, however at much lower allele frequencies compared to mutations in nuclear-encoded driver genes in the same samples. Also, extensive heterogeneity was observed among the heteroplasmic mtDNA variants present in an individual. We conclude that there is limited value in tracing tumor-specific mtDNA variants in blood-circulating cfDNA with the current methods available.

Sensitive detection of mitochondrial DNA variants for analysis of mitochondrial DNA-enriched extracts from frozen tumor tissue.

Large variation exists in mitochondrial DNA (mtDNA) not only between but also within individuals. Also in human cancer, tumor-specific mtDNA variation exists. In this work, we describe the comparison of four methods to extract mtDNA as pure as possible from frozen tumor tissue. Also, three state-of-the-art methods for sensitive detection of mtDNA variants were evaluated. The main aim was to develop a procedure to detect low-frequent single-nucleotide mtDNA-specific variants in frozen tumor tissue. We show that of the methods evaluated, DNA extracted from cytosol fractions following exonuclease treatment results in highest mtDNA yield and purity from frozen tumor tissue (270-fold mtDNA enrichment). Next, we demonstrate the sensitivity of detection of low-frequent single-nucleotide mtDNA variants (≤1% allele frequency) in breast cancer cell lines MDA-MB-231 and MCF-7 by single-molecule real-time (SMRT) sequencing, UltraSEEK chemistry based mass spectrometry, and digital PCR. We also show de novo detection and allelic phasing of variants by SMRT sequencing. We conclude that our sensitive procedure to detect low-frequent single-nucleotide mtDNA variants from frozen tumor tissue is based on extraction of DNA from cytosol fractions followed by exonuclease treatment to obtain high mtDNA purity, and subsequent SMRT sequencing for (de novo) detection and allelic phasing of variants.

Molecular diagnostics of the HBB gene in an Omani cohort using bench-top DNA Ion Torrent PGM technology.

Hemoglobinopathies, such as sickle cell disease (SCD) and beta-thalassemia major (TM), are severe diseases and the most common autosomal recessive condition worldwide and in particular in Oman. Early screening and diagnosis of carriers are the key for primary prevention. Once a country-wide population screening program is mandated by law, a sequencing technology that can rapidly confirm or identify disease-causing mutations for a large number of patients in a short period of time will be necessary. While Sanger sequencing is the standard protocol for molecular diagnosis, next generation sequencing starts to become available to reference laboratories. Using the Ion Torrent PGM sequencer, we have analyzed a cohort of 297 unrelated Omani cases and reliably identified mutations in the beta-globin (HBB) gene. Our model study has shown that Ion Torrent PGM can rapidly sequence such a small gene in a large number of samples using a barcoded uni-directional or bi-directional sequence methodology, reducing cost, workload and providing accurate diagnosis. Based on our results we believe that the Ion Torrent PGM sequencing platform, able to analyze hundreds of patients simultaneously for a single disease gene can be a valid molecular screening alternative to ABI sequencing in the diagnosis of hemoglobinopathies and other genetic disorders in the near future.

Limited role for histopathological examination of re-excision specimens of completely excised melanomas.

The Dutch melanoma guideline advises to examine one central block of the re-excision scar in case of a complete primary excision. To increase the evidence for this recommendation, we re-evaluated how often residual melanoma was found in re-excision specimens of a large series of completely excised melanomas. Of 1,209 Dutch melanoma cases, pathology reports of primary excisions were reviewed. Presence of melanoma in the margins was scored. All melanomas with a complete primary excision were included and pathology reports of re-excisions were reviewed. Presence of residual melanoma in the re-excision specimen and the number of blocks were scored. Slides of re-excision specimens containing residual melanoma were reviewed. Eventually, in four out of 812 melanomas (0.5 %) with a complete primary excision, residual melanoma was found in the re-excision specimen. The free margins of the primary melanomas in these cases ranged from 0.5-3.5 mm. In one case, the margin for melanoma in situ was 0.2 mm. In <1 % of initially completely excised melanomas, residual melanoma was found in the re-excision specimen. Histopathological examination of these re-excision specimens may not be cost-efficient. Our findings even imply that a re-excision could safely be omitted in selected cases of completely excised melanomas.

Risk of infection and sepsis in severely injured patients related to single nucleotide polymorphisms in the lectin pathway.

BACKGROUND: Infectious complications remain a serious threat to patients with multiple trauma. Susceptibility and response to infection is, in part, heritable. The lectin pathway plays a major role in innate immunity. The aim of this study was to assess whether single nucleotide polymorphisms (SNPs) in three key genes within the lectin pathway affect susceptibility to infectious complications in severely injured patients. METHODS: A prospective cohort of severely injured patients admitted to a level I trauma centre between January 2008 and April 2011 were genotyped for SNPs in MBL2 (mannose-binding lectin 2), MASP2 (MBL-associated serine protease 2) and FCN2 (ficolin 2). Association of genotype with prevalence of positive culture findings and infection was tested by χ(2) and logistic regression analysis. RESULTS: A total of 219 patients were included, of whom 112 (51·1 per cent) developed a positive culture from sputum, wounds, blood or urine. A systemic inflammatory response syndrome (SIRS) developed in 139 patients (63·5 per cent), sepsis in 79 (36·1 per cent) and septic shock in 37 (16·9 per cent). Patients with a MBL2 exon 1 variant allele were more prone to positive wound cultures (odds ratio (OR) 2·51, 95 per cent confidence interval 1·12 to 5·62; P = 0·025). A MASP2 Y371D DD genotype predisposed to SIRS (OR 4·78, 1·06 to 21·59; P = 0·042) and septic shock (OR 2·53, 1·12 to 4·33; P = 0·003). A FCN2 A258S AS genotype predisposed to positive wound cultures (OR 3·37, 1·45 to 7·85; P = 0·005) and septic shock (OR 2·18, 1·30 to 4·78; P = 0·011). CONCLUSION: Severely injured patients with SNPs in MBL2, MASP2 Y371D and FCN2 A258S of the lectin pathway of complement activation are significantly more susceptible to positive culture findings, and to infectious complications, SIRS and septic shock than patients with a wildtype genotype.

Methods to detect CNVs in the human genome.

The detection of quantitative changes in genomic DNA, i.e. deletions and duplications or Copy Number Variants (CNVs), has recently gained considerable interest. First, detailed analysis of the human genome showed a surprising amount of CNVs, involving thousands of genes. Second, it was realised that the detection of CNVs as a cause of genetic disease was often neglected, but should be an essential part of a complete screening strategy. In both cases new efficient CNV screening methods, covering the entire range from specific loci to genome-wide, were behind these developments. This paper will briefly review the methods that are available to detect CNVs, discuss their strong and weak points, show some new developments and look ahead. Methods covered include microscopy, fluorescence in situ hybridization (including fiber-FISH), Southern blotting, PCR-based methods (including MLPA), array technology and massive parallel sequencing. In addition, we will show some new developments, including a 1400-plex CNV bead assay, fast-MLPA (from DNA to result in approximately 6 h) and a simple Melting Curve Analysis assay to confirm potential CNVs. Using the 1400-plex CNV bead assay, targeting selected chromosomal regions only, we detected confirmed rearrangements in 9% of 320 mental retardation patients studied.

Complete sequencing of TP53 predicts poor response to systemic therapy of advanced breast cancer.

TP53 has been implicated in regulation of the cell cycle, DNA repair, and apoptosis. We studied, in primary breast tumors through direct cDNA sequencing of exons 2-11, whether TP53 gene mutations can predict response in patients with advanced disease to either first-line tamoxifen therapy (202 patients, of whom 55% responded) or up-front (poly)chemotherapy (41 patients, of whom 46% responded). TP53 mutations were detected in 90 of 243 (37%) tumors, and one-fourth of these mutations resulted in a premature termination of the protein. The mutations were observed in 32% (65 of 202) of the primary tumors of tamoxifen-treated patients and in 61% (25 of 41) of the primary tumors of the chemotherapy patients. TP53 mutation was significantly associated with a poor response to tamoxifen [31% versus 66%; odds ratio (OR), 0.22; 95% confidence interval (CI), 0.12-0.42; P < 0.0001]. Patients with TP53 gene mutations in codons that directly contact DNA or with mutations in the zinc-binding domain loop L3 showed the lowest response to tamoxifen (18% and 15% response rates, respectively). TP53 mutations were related, although not significantly, to a poor response to up-front chemotherapy (36% versus 63%; OR, 0.34; 95% CI, 0.09-1.24). In multivariate analysis for response including the classical parameters age and menopausal status, disease-free interval, dominant site of relapse, and levels of estrogen receptor and progesterone receptor, TP53 mutation was a significant predictor of poor response in the tamoxifen-treated group (OR, 0.29; 95% CI, 0.13-0.63; P = 0.0014). TP53-mutated and estrogen receptor-negative (<10 fmol/mg protein) tumors appeared to be the most resistant phenotype. Interestingly, the response of patients with TP53 mutations to chemotherapy after tamoxifen was not worse than that of patients without these mutations (50% versus 42%; OR, 1.35, nonsignificant). The median progression-free survival after systemic treatment was shorter for patients with a TP53 mutation than for patients with wild-type TP53 (6.6 and 0.6 months less for tamoxifen and up-front chemotherapy, respectively). In conclusion, TP53 gene mutation of the primary tumor is helpful in predicting the response of patients with metastatic breast disease to tamoxifen therapy. The type of mutation and its biological function should be considered in the analyses of the predictive value of TP53.

Entry of human cytomegalovirus into retinal pigment epithelial and endothelial cells by endocytosis.

PURPOSE: Human retinal pigment epithelial (RPE) cells and endothelial cells (HUVECs) are targets of human cytomegalovirus (HCMV) infection in vivo with significantly protracted replication in vitro compared with that in fibroblasts. This study analyzes the kinetics and mechanisms of HCMV entry into both cell types. METHODS: RPE cells were obtained from donor eyes. HUVECs were isolated from human umbilical cords. HCMV entrance was followed by electron microscopy and immunofluorescence in the presence of lysosomotropic agents and cytochalasin B. RESULTS: Human cytomegalovirus entered into RPE cells and HUVECs as early as 5 minutes after virus- cell contact. Entry was mediated by endocytosis, whereas HCMV enters fibroblasts through fusion. Most internalized viral particles and dense bodies appeared to be degraded within vacuoles. Viral entry, transport of viral proteins to the nucleus, and onset of viral transcription (immediate early [IE] protein expression) were significantly blocked by cytochalasin B. Lysosomotropic agents did not significantly reduce IE expression in RPE cells or HUVECs. CONCLUSIONS: This study shows that HCMV penetrates these highly specialized relevant cells via endocytosis. The low level of infection and the delay in the onset of HCMV expression seen in these cells compared with fibroblasts may be related to the sequestration and degradation of incoming viral particles in endocytic vacuoles.

Optimized non-radioactive protein truncation test for mutation analysis of the adenomatous polyposis coli (APC) gene.

Germline mutations in the adenomatous polyposis coli gene cause familial adenomatous polyposis, a colon cancer predisposition syndrome. More than 95% of the identified mutations result in the generation of stop codons or reading frame shifts and encode a truncated gene product, a mutation profile also found in other tumor predisposition genes such as the breast cancer or the hereditary non-polyposis coli. Therefore the protein truncation test is ideally suited for screening of mutations in these genes, starting from simple blood samples. Gene segments of interest are amplified from genomic DNA or mRNA, thereby incorporating a T7 promoter at the 5'-end. After in vitro transcription and translation of the PCR products, the resulting protein is analysed by gel electrophoresis. Truncated translation products indicate the presence of a stop mutation. We have developed a non-radioactive protein truncation test that uses a biotinylated Lys-t-RNA to label the translation products and allows a chemiluminescent detection instead of the standard radioactive method. This generic protein truncation test kit was then used to develop a parameter-specific protein truncation test for adenomatous polyposis coli. The adenomatous polyposis coli gene was divided in 5 overlapping segments, and primers were optimized to produce distinct bands with very low background in the protein truncation test. The assay was tested on 20 familial adenomatous polyposis patient samples, where 18 mutations were found, demonstrating the efficiency of this method.

Nuclear import as a barrier to infection of human umbilical vein endothelial cells by human cytomegalovirus strain AD169.

Human embryonal fibroblasts (HEF) are fully permissive for infection by human cytomegalovirus (HCMV) strain AD169, whereas human umbilical vein endothelial cells (HUVEC) seem to form an almost complete barrier to infection with this virus. To investigate this difference in permissiveness, HCMV infection of both cell types was studied using in situ hybridisation (ISH) as well as immunocytochemistry to detect viral DNA and viral proteins. At 2 h post-infection (p.i.), viral DNA was detected dispersed throughout the cytoplasm in both HEF and HUVEC, indicating that HCMV enters all cells of both cell types. At 4 h p.i., the viral DNA was found in the nucleus in HEF, and at the same time expression of immediate early (IE) antigen was found. In contrast, in HUVEC the expression of the IE proteins occurred in a limited number of cells at 8 h p.i., while in most HUVEC an accumulation of viral DNA around the nuclei was observed at this time point. In HUVEC, the nuclear localisation of viral DNA was detected 16 h p.i. in a minority of cells, indicating that transport of HCMV DNA into the nucleus is considerably slower in HUVEC than in HEF. Furthermore, the number of HUVEC containing HCMV DNA decreased about six-fold between 8 and 48 h p.i., indicating that HCMV DNA is either transported into the nucleus or eliminated. Apparently, the lower permissiveness of HUVEC for the HCMV strain AD169 relative to HEF is due to inefficient transport of HCMV DNA into the nuclei of infected HUVEC.

Intracellular thiol redox status affects rat cytomegalovirus infection of vascular cells.

There is increasing evidence for cytomegalovirus (CMV) induced vascular pathology during acute infection in the immunocompromised host. Inflammation is involved in such processes, which is frequently associated with increased levels of oxidative mediators and reduced anti-oxidant protection. A relation between viral infection and oxidative stress has been recognized for human immunodeficiency virus and herpes simplex virus-1 infections, but little is known in this respect for CMV infections. We investigated if there is a relation between CMV infection of vascular cells and the intracellular redox status using an in vitro rat model. We measured intracellular glutathione levels and rat CMV (RCMV) permissiveness of rat heart endothelial cell lines (RHEC), rat smooth muscle cells (RSMC), and compared these with fully CMV-permissive rat fibroblasts (REF and Rat 2). In addition, the effects of the anti-oxidant N-acetylcysteine (NAC) and the glutathione synthesis inhibitor buthionine sulfoximide (BSO) on CMV permissiveness and replication were investigated in these cell lines. Finally, we investigated infection of vascular cells under inflammatory conditions in an in vivo rat model for acute CMV infection. The results show a very high endogenous glutathione level in RHEC compared to REF, Rat 2 cells and RSMC. This is associated with a low CMV permissiveness in RHEC as opposed to full permissiveness in REF, Rat 2 cells and RSMC in vitro. In addition, modulation of the intracellular thiol redox status affected CMV infection and replication only in RHEC, but not in RSMC and Rat 2 cells. During acute infection in vivo under immunosuppressed conditions rat endothelial cells first become activated and subsequently infected leading to vascular damage and pathology. This study suggests that a high endogenous thiol redox status may contribute to the apparent barrier function of endothelial cells with respect of CMV infection and that oxidative stress may facilitate CMV infection of the vascular wall.

Activation of protein kinase C enhances the infection of endothelial cells by human cytomegalovirus.

The infection of cultured endothelial cells with human cytomegalovirus (HCMV) is generally limited to less than 10% of the cells in contrast to HCMV infection of fibroblasts, where essentially all cells can be infected. It is known that HCMV infection influences a number of signal transduction pathways of infected cells. We therefore questioned whether, conversely, the infectivity of human umbilical vein endothelial cells could be influenced by the deliberate activation of these pathways. When endothelial cells were treated prior to infection with phorbol myristoyl acetate, an activator of protein kinase C, the number of HCMV-positive cells increased two to three times. On the other hand, pretreatment of the cells with RO 31-8220, a specific protein kinase C inhibitor, or with staurosporine, a general protein kinase inhibitor, resulted in a decreased infection level and in abolishment of the PMA-induced effect. Pretreatment with the protein phosphatase inhibitor, okadaic acid, caused a slight increase in infectivity, whereas pretreatment with the protein tyrosine kinase inhibitor, genistein, was without effect. Furthermore, neither forskolin and ilomedine, compounds known to activate the endothelial adenylate cyclase, nor the calcium ionophore A23187 were able to influence HCMV infectivity. It is concluded that: (a) the HCMV infection level of unstimulated endothelial cells is influenced by the basal level of protein kinase C; and (b) stimulation of protein kinase C prior to infection results in an increase of infection by HCMV.

A dual role for endothelial cells in cytomegalovirus infection? A study of cytomegalovirus infection in a series of rat endothelial cell lines.

Several clinical findings point to the involvement of microvascular endothelial cells in cytomegalovirus-related pathology. In this study the interactions of cytomegalovirus (CMV) with microvascular endothelial cells was investigated in an in vitro rat model. A series of rat endothelial cell lines, considered representative for the heterogeneity of heart microvascular endothelium in vivo, were infected with rat CMV (RCMV). The course of infection and production of infectious virus were examined using immunofluorescence staining and plaque titration assays, and was compared with infection of fully permissive rat fibroblasts. These endothelial cell lines displayed differences in susceptibility to CMV infection. Two endothelial cell lines (RHEC 50 and 191) were practically non-permissive, while four endothelial cell lines (RHEC 3, 10, 11 and 116) were partly permissive for CMV infection. In contrast to CMV infection in fibroblasts, only limited infection of the permissive endothelial cell lines was observed without spreading of CMV infection through the monolayer, although infectious virus was produced. Detachment of infected endothelial cells and recovery of the monolayer with time was observed. The detached endothelial cells were able to transmit CMV infection to fibroblast monolayers, but not to endothelial monolayers. Our in vitro results demonstrate differences in permissiveness for RCMV between the series of rat endothelial cell lines, which is suggestive for endothelial heterogeneity to CMV infection in vivo. Our findings indicate that endothelial cells are relatively resistant to CMV infection and that, upon infection, the endothelial monolayer may dispose of the virus via detachment of the infected cells. This points to a dual role for the endothelium in CMV infection in vivo: a barrier for CMV infection (by the endothelial monolayer) on the one hand and spreading of CMV infection (by detached infected cells) on the other hand.

Polyunsaturated fatty acids and function of platelets and endothelial cells.

Fish oil diets, rich in n-3 polyunsaturated fatty acids, are considered to have an antithrombotic effect. Both platelets and endothelial cells play a crucial role in the regulation of thrombosis and haemostasis. There is substantial evidence that, in these cells, fish oil-derived polyunsaturated fatty acids can replace the n-6 polyunsaturated fatty acid, arachidonic acid, in the membrane phospholipids and can modify those cellular reactions in which the latter fatty acid participates. However, it now appears that dietary n-3 polyunsaturated fatty acids are less potent than, for example, aspirin in modifying the activation properties of these cell systems. This suggests the possible involvement of additional cells or factors in mediating the antithrombotic potential of fish oil fatty acids.

Cytomegalovirus infection and vessel wall pathology.

This review focuses on information regarding the cytomegalovirus (CMV) in relation to vessel wall pathology including clinical symptoms, pathogenesis and latency. Evidence obtained for involvement of CMV in vascular pathology will be summarized. CMV infection of vascular cells induces cell activation, which leads to expression of adhesion proteins, MHC molecules, cytokine receptors and the production of cytokines and growth factors. Furthermore, CMV infection enhances the inflammatory response and neointima formation in allograft vessels. From such data it can be hypothesized that there is apparently synergy between inflammatory processes and CMV infection. On the one hand, CMV infection leads to cellular activation, on the other hand inflammatory processes contribute to CMV infection. NF-kappa B-dependent activation may form a link between both processes as it would induce CMV replication and host cell activation. Thus, CMV may influence vascular pathology by enhancing the inflammatory process and cellular activation responses.