Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population.

BACKGROUND: Low-grade inflammation is thought to contribute to the development of cardiovascular disease (CVD), type-2 diabetes mellitus (T2D), cancer and mortality. Biomarkers of inflammation may aid in risk prediction and enable early intervention and prevention of disease. OBJECTIVE: The aim of this study was to investigate whether plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) are predictive of disease and mortality in the general population. DESIGN: This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006. SETTING: General adult Caucasian population. PARTICIPANTS: The MONICA10 study, a population-based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years. MEASUREMENTS: Blood samples were analysed for suPAR levels using a commercially available enzyme-linked immunosorbent assay. Risk of cancer (n = 308), CVD (n = 301), T2D (n = 59) and mortality (n = 411) was assessed with a multivariate proportional hazards model using Cox regression. RESULTS: Elevated baseline suPAR level was associated with an increased risk of cancer, CVD, T2D and mortality during follow-up. suPAR was more strongly associated with cancer, CVD and mortality in men than in women, and in younger compared with older individuals. suPAR remained significantly associated with the risk of negative outcome after adjustment for a number of relevant risk factors including C-reactive protein levels. LIMITATION: Further validation in ethnic populations other than Caucasians is needed. CONCLUSION: The stable plasma protein suPAR may be a promising biomarker because of its independent association with incident cancer, CVD, T2D and mortality in the general population.

Trichinella infection in a hunting community in East Greenland.

Trichinella nativa infection (trichinellosis) is highly prevalent in Arctic wildlife, but the human burden of trichinellosis in present-day Greenland is unknown. The study aimed to determine Trichinella seroprevalence in an eastern Greenlandic hunting community and to evaluate risk factors for seropositivity. Overall, 998 inhabitants aged 10 years in the Ammassalik municipality were tested for Trichinella-specific IgG antibodies. Background information was obtained from questionnaires. Seropositivity was 1.4% in persons aged <40 years and increased to >12% in those aged 60 years. Older age, occupation as hunter or fisherman, and consumption of polar bear meat significantly increased the risk of Trichinella seropositivity. The seropositivity age pattern probably reflects changes in dietary preferences, but could also reflect mandatory meat inspection since 1966. However, preventive measures against Trichinella infection should be strengthened in Greenland.

Human antibody recognition of Anisakidae and Trichinella spp. in Greenland.

High levels of total IgE are observed among children in Greenland. To evaluate the extent to which Anisakidae and Trichinella spp. contribute to the high total IgE level, an ELISA and a western blot were developed for the detection of IgG antibodies to Anisakidae, based on excretory/secretory antigens from Anisakidae larvae. Western blots with Anisakidae and Trichinella antigens discriminated between Anisakidae and Trichinella infections, enabling cross-reactivity between the two parasite infections to be eliminated. Serum samples from 1012 children in Greenland were analysed for specific antibodies to Anisakidae and Trichinella. Eleven children were IgG-positive for Trichinella and nine were IgG-positive for Anisakidae, indicating a relatively low prevalence of both infections among children in Greenland. Faecal samples from 320 children were also examined for other intestinal parasites. Enterobius vermicularis was found in one sample and Blastocystis hominis in 32 samples, but no other intestinal parasites were identified. In total, 304 children had elevated total IgE levels. There was a significant association between Trichinella seropositivity and high levels of total IgE, but not between Anisakidae seropositivity and total IgE. The data indicate that parasitic infections alone do not explain the high level of total IgE observed among children in Greenland.

Comparison of two antigens for demonstration of Trichinella spp. antibodies in blood and muscle fluid of foxes, pigs and wild boars.

For the surveillance of trichinellosis, the digestion method is reliable but also labour intensive. The serological methods for the detection of Trichinella-specific antibodies using ELISA offer a sensitive and relatively specific alternative. For serological studies, sera or plasma from blood samples are the most common source of antibodies, but although the concentration of antibodies is approximately 10-fold lower, muscle fluid can be a good alternative particularly for testing of wildlife samples. In the present study, an indirect ELISA technique was evaluated on both sera and muscle fluids from experimentally infected foxes, pigs, and wild boars using both excretory/secretory (E/S) antigens and a synthetic glycan antigen, beta-tyvelose. Although the synthetic antigen appears to be less sensitive than the E/S antigens, Trichinella-specific IgG antibodies were detected in both serum samples and muscle fluid samples from pigs, wild boars and foxes infected at levels which would be important for food safety or represent a significant reservoir for further transmission.

Serological evidence of Trichinellosis in local pigs of Nepal.

In Nepal, animal husbandry is a major source of income. Pig husbandry is practiced in rural, peri-urban, and urban communities. Free ranging "back yard" pigs and the practice of feeding offal is a very common management practice which potentially allows for the transmission of trichinellosis; however, this zoonosis has never been reported from this region. A total of 425 serum samples were collected from local pigs. These were initially screened by ELISA after which positive samples were examined by Western blot. This procedure identified two samples which had clear specific bands for Trichinella; however, muscle samples tested by HCL-pepsin digestion were found to be negative. If these highly specific serological analyses are confirmed, this would be the first report of trichinellosis in Nepal and a prevention program should be initiated to limit the access of pigs to open garbage dumps which exist both in towns and on farms.

Hospital volume and outcome of rectal cancer surgery in Denmark 1994-99.

OBJECTIVE: The association between hospital volumen and outcome of major cancer surgery is being debated at present. We analysed the outcome of rectal cancer surgery in Denmark during the period 1994-99. METHODS: All patients with a first-time rectal cancer were registered in a national database during the 5-year period. In this observational cohort study, the influence of hospital case volume on resectional procedure, complications, 30-day mortality and 5-year mortality was analysed. RESULTS: The register comprised 5021 patients. Surgery was performed in 27 hospitals with <15 operations per year, 15 hospitals with 15-30 operations per year and 11 hospitals with >30 operations per year. In a multivariate model, the risk of permanent colostomy was significantly increased in the group of low-volume hospitals. On the contrary, volume did not influence the risk of anastomotic leakage, 30-day mortality and 5-year mortality. However, a large variation in 5-year mortality was observed particularly within the low-volume group of hospitals. CONCLUSIONS: In this study, only risk of having a permanent colostomy during surgery for rectal cancer was significantly related to hospital case volume. When individual hospitals were analysed, a large variation in 5-year mortality was observed within the low-volume group of hospitals.

Survival of rectal cancer patients in Denmark during 1994-99.

OBJECTIVE: As survival from rectal cancer in Denmark is below the European average, we analysed survival during the period of 1994-99 focusing upon improvement strategies. METHOD: All patients with a first-time rectal cancer were registered in a national database during this 5-year period. In the observational cohort study, data on patient age and gender, tumour stage, surgical procedures, adjuvant radiotherapy, anastomotic leakage, 30-day mortality and long-term survival were evaluated. RESULTS: The database comprised 5021 patients. Sixty-four percent had a localized tumour. Less than a third of patients with fixed tumours had pre-operative radiotherapy and curative surgery was achieved in 70%. Anastomotic leakage occurred in 13%, and 30-day mortality was 4% following abdominoperineal or anterior resection and 11% following a Hartmann's procedure. The relative 5-year survival in the entire series was 39% in males and 47% in females, respectively. Following curative surgery the relative 5-year survival was 55% in males and 63% in females, respectively. Survival was 71% in the subset of patients receiving curative total mesorectal excision. CONCLUSION: The average tumour stage upon diagnosis was probably more advanced compared to the other Nordic countries and pre-operative radiotherapy was administered to a minority of patients with fixed tumours. The anastomotic leakage rate was relatively high, whereas the 30-day mortality was comparable to other studies. Survival from rectal cancer in Denmark is still less favourable compared to the other Nordic and several European countries but improved from 1996 and onwards.

Experimental Trichinella infection in seals.

The susceptibility of seals to infection with Trichinella nativa and the cold tolerant characteristics of muscle larvae in seal meat were evaluated. Two grey seals, Halichoerus grypus, were inoculated with 5000 (100 larvae/kg) T. nativa larvae and two grey seals with 50000 (1000 larvae/kg). One seal from each dose group and two control seals were killed at 5 and 10 weeks post-inoculation (p.i.). At 5 weeks p.i., infection was established in both low and high dose seals with mean larval densities of 68 and 472 larvae per gram (lpg), respectively, using eight different muscles for analyses. At 10 weeks p.i., mean larval densities were 531 and 2649 lpg, respectively, suggesting an extended persistence of intestinal worms. In seals with high larval density infections, the distribution of larvae in various muscles was uniform, but in one seal with a low larval density infection, predilection sites of larvae included muscle groups with a relative high blood flow, i.e. diaphragm, intercostal and rear flipper muscles. Trichinella-specific antibody levels, as measured by ELISA, increased during the 10 week experimental period. Infected seal muscle was stored at 5, -5 and -18 degrees C for 1, 4 and 8 weeks. Muscle larvae released from stored seal muscle by artificial digestion were inoculated into mice to assess viability and infectivity. Larvae from seal muscle 10 weeks p.i. tolerated -18 degrees C for 8 weeks but larvae from seal muscle 5 weeks p.i. tolerated only 1 week at -18 degrees C, supporting the hypothesis that freeze tolerance increases with the age of the host-parasite tissue complex. The expressed susceptibility to infection, extended production of larvae, antibody response and freeze tolerance of T. nativa in seals are new findings from the first experimental Trichinella infection in any marine mammal and suggest that pinnipeds (phocids, otariiids or walrus) may acquire Trichinella infection by scavenging even small amounts of infected tissue left by hunters or predators.