Antibodies to infectious agents and the positive symptom dimension of subclinical psychosis: The TRAILS study

Infections have been suggested to play a role in the etiology of schizophrenia, but the evidence for this has been inconsistent. Schizophrenia patients have an increased risk of infections as a result of hospitalizations or life style factors. Therefore a study on early subclinical manifestations of psychosis in relation to virus infections is warranted. We examined whether serum antibodies against human Herpes viruses and Toxoplasma gondii were associated with subclinical symptoms of psychosis in adolescents. Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective cohort of Dutch adolescents. A total of 1176 participants with an available Community Assessment of Psychic Experiences (CAPE) and an available blood sample were included in this analysis. Solid-enzyme immunoassay methods were used to measure the presence of immunoglobulin G (IgG) antibodies in serum to the Herpes virus family and to T. gondii. There was no significant association between serologic evidence of infection with human Herpes viruses or T. gondii and the risk of subclinical positive experience of psychosis. Subjects with a positive serological reaction to Epstein-Barr Virus (EBV) had higher scores on the positive dimension of psychosis measured by CAPE (b=0.03, P=0.02). This significant association was observed in males, but not in females. The current study suggests that there is no significant association between serological evidence of infection to human Herpes viruses and positive subclinical experience of psychosis, whereas there was an association between EBV infection and subclinical psychotic symptoms in boys.     

Results of treatment of patients with gestational trophoblastic neoplasia referred to the Brewer Trophoblastic Disease Center after failure of treatment elsewhere (1979-2006)

OBJECTIVE: To review treatment results of patients with gestational trophoblastic neoplasia (GTN) whose care was transferred to the Brewer Trophoblastic Disease Center after failure of treatment elsewhere from 1979-2006. STUDY DESIGN: Twenty-seven (6.6%) of 408 patients with GTN treated at the Brewer Center from 1979-2006 had received unsuccessful treatment at other institutions prior to transfer to our center. Outcomes were analyzed and compared with 37 patients who received secondary therapy at the Brewer Center from 1962-1978. RESULTS: Overall survival was 93% (25 of 27) in patients treated at the Brewer Center (1979-2006) after failed treatment elsewhere. The most common causes of treatment failure prompting referral to the Brewer Center were (1) use of a single-agent chemotherapy protocol to treat high-risk disease in 11 patients (41%), (2) inappropriate use of weekly methotrexate chemotherapy in 9 patients (33%), (3) failed sequential single-agent chemotherapy in 4 patients (15%), (4) use of the wrong multiagent chemotherapy for high-risk disease in 1 patient (4%) and (5) relapse from remission in 2 patients CONCLUSION: Successful secondary treatment of GTN improved from 59% during 1962-1978 to 93% during 1979-2006 as a result of better chemotherapy protocols and experience treating the disease.     

Dearterialization of the liver causes intrahepatic cholestasis due to reduced bile transporter expression

BACKGROUND: Bile duct injury after hepatic artery thrombosis (HAT) in liver transplantation is believed to be caused by ischemia predominantly. We aimed to define the involvement of bile secretory dysfunction in the pathogenesis of liver injury after HAT. METHODS: In a murine model, the main hepatic artery, the extrahepatic peribiliary plexus, or both arterial connections to the liver were interrupted (n=5 for each group). After 1, 14, or 28 days, hepatobiliary function was assessed by analysis of bile transporter expression, serum bile acids and bilirubin, and hepatic ATP content. In addition, cellular injury was assessed by light microscopy and biochemical markers. RESULTS: There were no signs of hepatobiliary dysfunction or injury in sham-operated animals or in mice with interruption of the hepatic artery or the extrahepatic peribiliary plexus alone. However, as early as 24 hr after complete dearterialization, bile transporter expression was significantly reduced and intrahepatic cholestasis started to progress the following weeks. Histologic studies at 28 days after complete dearterialization showed severe hepatobiliary injury. CONCLUSIONS: This study indicates that arterial blood supply is critical for normal bile secretion. Bile duct injury after complete arterial deprivation is preceded by a loss of bile secretory function and subsequent intrahepatic cholestasis.     

Exploring the role of polymorphisms in ficolin genes in respiratory tract infections in children

Ficolins are pattern‐recognition molecules that appear to be relevant for innate immune defence against infections. The ficolin genes in Caucasians are polymorphic and genetic variations may have functional consequences, both in relation to function and concentration. Low levels of Ficolin‐2 have been suggested to associate with recurrent respiratory tract infections (RTI), whereas data on Ficolin‐3 are still very limited. We investigated the association between variation in genes encoding Ficolin‐2 (FCN2) and Ficolin‐3 (FCN3) and frequency of RTI during the first 4 years of life. The study population consisted of 900 children from a large, population‐based birth cohort of Dutch children, followed prospectively from birth to 4 years of age. The number of RTI was assessed by annual parental questionnaires. Nine single nucleotide polymorphisms in FCN2 and two in FCN3, all based on functionality or haplotype‐tagging characteristics, were determined and haplotypes constructed. We found that single nucleotide polymorphisms in FCN2 and FCN3 were not associated with increased risk of RTI during the first 4 years of life. No difference existed between haplotype‐frequencies of FCN2 and FCN3 in children grouped according to the reported number of RTI. In conclusion, at a population level, genetic variation in ficolin genes FCN2 and FCN3 do not seem to contribute to the risk of RTI in Caucasian children.