Risk factors of endoleak following endovascular repair of abdominal aortic aneurysm. A multicentric retrospective study

Endoleak (EL) represents the most common complication following endovascular abdominal aortic aneurysm repair (EVAR). Unfortunately, the long-term results of EVAR and its durability have been questioned, and EL are variably associated with a risk of late failure. The aim of this retrospective study was to identify risk factors for this complication of aneurysm-endograft complex in patients who underwent EVAR. A group of 104 consecutive patients (99 men, 5 women; median age, 74 years; range, 50-89 years) were enrolled in the study. Both preoperative and follow-up imaging studies were obtained using helical computed tomography scanning at 1, 6, 12, 24, 36 months after EVAR and blindly reviewed by a surgeon and a radiologist. Twenty-seven (25.9%) patients developed EL during follow-up, of which 10 (37%) were primary (<30 days from EVAR), and 17 (63%) were secondary EL. Age and smoking did not affect the EL onset, while a body mass index >25 and a history or presence of arterial hypertension represented significant (p<0.05) risk factors. Moreover, both greatest diameter and maximum length of the aneurysm were significantly higher (p<0.01) in patients who developed EL. No relationship was found with the anatomical features of the aortic neck (i.e. length and diameter), and between the initial size of the aneurysm and the dimension at the time of EL. In conclusion, in our study, being overweight, arterial hypertension and the initial size of the aneurysm represent risk factors for EL development.     

The changing epidemiology of severe cytomegalovirus disease in Australia

Few studies have reported the epidemiological characteristics and burden of severe cytomegalovirus (CMV) in the hospital setting. This study used data compiled by the Australian Institute of Health and Wealthfare(1) to examine the trends in hospital admissions due to CMV in different patient groups. As CMV disease mainly occurs in high-risk populations and almost always results in hospitalization, hospital data are an appropriate source of information on the epidemiology of clinically relevant disease. The study found that between 1993 and 2001 the average annual rate of hospital admissions where CMV was identified as the principal reason for admission amounted to 14.2 cases per 100,000 populations. This rate varied between 21.6 (1993/94) and 2.0 (2000/01) per 100,000 per year, and was always somewhat higher for men compared to women. The average annual incidence of children admitted to hospital with congenital CMV (principal and secondary diagnosis) in children aged 0-4, 5-9 and 10-14 years was 1.4, 1.3 and 0.4 per 100,000 respectively. Correlations with Human Immunodeficiency Virus (HIV), organ transplantation and other causes of immuno-suppression were also examined. The burden of severe CMV disease in Australia was found to be significant and comparable to other diseases for which national vaccination programs exist. As new vaccines for CMV may soon be available, understanding the pre-vaccination burden of CMV disease is useful for planning a vaccination program should a suitable vaccine be developed.     

Antioxidant, anti-inflammatory and anticancer activities of methanolic extracts from Ledum groenlandicum Retzius

Labrador tea (Ledum groenlandicum Retzius) is an ericaceae widely distributed in North America. The leaves and twigs were used in Native American traditional medicine to treat several inflammatory pathologies such as asthma, rheumatisms and burns. Reactive oxygen species as well as reactive nitrogen species such as nitric oxide (NO) contribute significantly to these pathologies. In this study, the antioxidant, anti-inflammatory and anticancer activities of crude methanol extracts of leaves and twigs from Ledum groenlandicum were investigated. Both extracts showed a strong antioxidant activity using the ORAC method and a cell based-assay. Moreover, the twig and leaf extracts showed significant anti-inflammatory activity, inhibiting NO release, respectively, by 28 and 17% at 25 microg/ml in LPS-stimulated RAW 264.7 macrophages. In comparison, N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, reduced NO release by 24% at 25 microg/ml. The twig extract was also found to be active against DLD-1 colon carcinoma and A-549 lung carcinoma cells, with IC(50) values of 43+/-1 and 65+/-8 microg/ml, respectively. The bioguided study of the twig extract resulted in the isolation and identification of ursolic acid, a known triterpene. Ursolic acid was active against DLD-1 (IC(50): 9.3+/-0.3 microM) and A-549 (IC(50): 8.9+/-0.2 microM), suggesting it is, in part, responsible of the anticancer activity of the twig extract.     

The effects of midazolam on the acquisition and expression of fructose- and maltodextrin-based flavour preferences

The effects of the benzodiazepine agonist midazolam on the acquisition and expression of flavour preferences were investigated. Rats (Experiment 1) were given one-bottle training with one flavoured solution (CS+) mixed with either fructose or maltodextrin and another solution (CS-) presented alone. Animals receiving 1 mg/kg midazolam during training consumed more CS- than did animals receiving vehicle injections although there was no drug effect on CS+ consumption. In two-bottle tests the CS+ was preferred to the CS- with the preference being larger in fructose trained animals. Midazolam (0.3-3 mg/kg) increased total intake but not CS+ preference. Training under midazolam reduced the CS+ preference when fructose, but not maltodextrin, was the reinforcer. In Experiment 2 training consumption was restricted to 10 ml/session. This removed the difference in CS+ preference between reinforcer types but otherwise the results were as in Experiment 1. The midazolam induced attenuation of fructose-based preferences might reflect an increase in CS- palatability during training which would reduce the difference between the reinforced and non-reinforced solutions. As maltodextrin supports preferences due to post-ingestive effects manipulation of palatability should be ineffective. Midazolam does not influence the expression of conditioned flavour preferences despite prior evidence that benzodiazepine agonists enhance palatability.     

Mendelian and complex genetics of susceptibility and resistance to parasitic infections

Uncovering the complex genetic basis of susceptibility and resistance to parasitic infectious diseases is an enormous challenge. It probably involves many different host genes, interacting with multiple parasite genetic and environmental factors. Several genes of interest have been identified by family and association studies in humans and by using mouse models, but more robust epidemiological studies and functional data are needed to authenticate these findings. With new technologies and statistical tools for whole-genome association analysis, the next few years are likely to see acceleration in the rate of gene discovery, which has the potential to greatly assist drug and vaccine development.     

Genetically increased risk of sleep disruption in Alzheimer's disease

STUDY OBJECTIVES: To investigate the role of a monoamine A oxidase promoter polymorphism in sleep disruption in Alzheimer's disease (AD). DESIGN: A case-control association analysis. SETTING: Sleep disturbance in AD is common, is extremely stressful for caregivers, and increases the risk of institutionalisation. It remains unclear why only some patients develop sleep disturbance; neuropathologic changes of AD are not typically seen in the areas of the brain responsible for sleep. We hypothesized that the risk of sleep disturbance is, at least in part, influenced by the availability of serotonin used for melatonin synthesis secondary to polymorphic variation at the enzyme monoamine oxidase A (MAO-A). PATIENTS: Patients with AD diagnosed according to standard criteria. INTERVENTIONS: Data were collected using the Sleep domain of the Neuropsychiatric Inventory with Caregiver Distress. Patients' cognition and function were assessed using the Mini-Mental State Examination and the Functional Assessment Staging. Genotyping of apolipoprotein E (APOE) and of the 30 bp variable number tandem repeat of the MAO-A promoter was by standard methods. MEASUREMENTS AND RESULTS: Of 426 patients surveyed, 54% experienced sleep disturbance. We found that the high-activity 4-repeat allele of the MAO-A VNTR promoter polymorphism confers increased susceptibility to sleep disturbance (p = .008). A quantitative sleep disturbance score was significantly higher in the patients possessing MAO-A 4-repeat allele genotypes. APOE had no influence on the development of an altered sleep phenotype. CONCLUSIONS: We conclude that sleep disturbance in AD is common and distressing and is associated with genetic variation at MAO-A.     

Similarities in the immunoglobulin response and VHgene usage in rhesus monkeys and humans exposed to porcine hepatocytes

Background

Leukocytes commonly infiltrate solid tumors, and have been implicated in the mechanism of spontaneous regression in some cancers. Conventional techniques for the quantitative estimation of leukocyte infiltrates in tumors rely on light microscopy of immunostained thin tissue sections, in which an arbitrary assessment (based on low, medium or high levels of infiltration) of antigen density is made by the pathologist. These estimates are relatively subjective and often require the opinion of a second pathologist. In addition, since thin tissue sections are cut, no data regarding the three-dimensional distribution of antigen can be obtained.

Results

To overcome these problems, we have designed a method to enumerate leukocyte infiltration into tumors, using confocal laser scanning microscopy of fluorescently immunostained leukocytes in thick tissue sections. Using image analysis software, a threshold was applied to eliminate unstained tissue and residual noise. The total antigen volume in the scanned tissue was calculated and divided by the mean cell volume (calculated by "seeding" ten individual cells) to obtain the cell count. Using this method, we compared the calculated leukocyte counts with those obtained manually by ten laboratory personnel. There was no significant difference (P > 0.05) between the cell counts obtained by either method. We then compared leukocyte infiltration into seven tumors and matched non-malignant tissue obtained from the periphery of the resected tissue. There was a significant increase in the infiltration of all leukocyte subsets into the tumors compared to minimal numbers in the non-malignant tissue.

Conclusion

From these results we conclude that this method may be of considerable use for the enumeration of cells in tissues. Furthermore, since it can be performed by laboratory technical staff, less time input is required by the pathologist in assessing the degree of leukocyte infiltration into tumors.     

Immune response in rhesus macaques after mixed modality immunisations with DNA, recombinant adenovirus and recombinant gp120 from human immunodeficiency virus type 1

The establishment of effective regimens for a vaccine against human immunodeficiency virus type 1 (HIV-1) is urgently needed. In the present study we have produced HIV-1 gp120 from a vaccine-relevant primary R5 isolate in recombinant vaccinia (rVV)-infected Vero cells. We have investigated the effect of boosting with this protein in mixed modality immunisations of rhesus macaques following different immunisation. As reported earlier, animals were primed with codon-optimised HIV-1(BX08)env DNA delivered as plasmid or as replication-deficient recombinant human adenovirus type 5 (rAd5), which both induced specific antibody and cellular immune responses (1). Boosting with rAd5 temporarily had increased the anti-gp120 antibody titres approximately 1 log (rAd5+rAd5) or 3 log (DNA+rAd5) (1). However, secondary rAd5 boosting showed less effect due to the induced vector-specific immunity. To further boost the antibody response, the rgp120(BX08) was injected with Quadri A saponin adjuvant. The protein boosting resulted in a 1-2 log antibody increase and also boosting of the cell-mediated immune response. Neutralising antibodies to the heterologous HIV-1(MN) were detected; however, neutralising antibodies to the primary HIV-1(Bx08) isolate were seen only transiently after rAd5 but not the rgp120 immunisation. It is concluded that the rgp120(Bx08) reagent from rVV-infected Vero cells is functional and immunogenic in macaques, inducing both antibody and cellular immunity. The rgp120(Bx08) is a relevant model antigen that may be used to boost antibody and cellular immunity in mixed modality vaccine regimens against HIV-1 in higher animals.