Magnetic resonance imaging with optical preamplification and detection.

Magnetic resonance (MR) imaging relies on conventional electronics that is increasingly challenged by the push for stronger magnetic fields and higher channel count. These problems can be avoided by utilizing optical technologies. As a replacement for the standard low-noise preamplifier, we have implemented a new transduction principle that upconverts an MR signal to the optical domain and imaged a phantom in a clinical 3 T scanner with signal-to-noise comparable to classical induction detection.

The HLA-DR3,DQ2 heterozygous genotype is associated with an accelerated progression of primary sclerosing cholangitis.

BACKGROUND: An improvement of prognostic models in primary sclerosing cholangitis (PSC) is needed. In particular, inclusion of prognostic markers that are independent of the disease stage would be advantageous. We investigated whether HLA class II genes associated with PSC are also related to disease progression. METHODS: The study included 265 PSC patients from five European countries with a median follow-up of 9.1 years. The end-points were death (n = 38) or liver transplantation (n = 52). Thirty patients developed cholangiocarcinoma during follow-up. RESULTS: The DRB1*03,DQA1*0501, DQB1*02 (i.e. DR3,DQ2) heterozygous genotype was associated with an increased risk of death or liver transplantation (hazard ratio = 1.63; 95% confidence interval (CI) = 1.06-2.52). The presence of a DQ6 encoding haplotype (DQB1*0603 or DQB1*0602) in DR3,DQ2 negative individuals was associated with a reduced risk of death or liver transplantation (hazard ratio = 0.57; 95% CI = 0.36-0.88). There was a trend towards an increased risk of developing cholangiocarcinoma among DR4,DQ8 positive patients, but this did not reach significance (odds ratio = 2.27; 95% CI = 0.78-6.62). CONCLUSION: The DR3,DQ2 heterozygous genotype is associated with a more rapid progression of PSC, whereas HLA-DQ6 is associated with a retarded disease progression. It is possible that the DR4,DQ8 haplotype is related to cholangiocarcinoma development.

Increased frequency of autoimmune diseases in patients with primary sclerosing cholangitis.

OBJECTIVES: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown origin that mostly affects male patients with inflammatory bowel disease (IBD). The immune system is believed to be involved in the etiology/pathogenesis as these patients present with several immunological disturbances. Susceptibility to develop primary sclerosing cholangitis is partly determined by genes in the HLA complex. The aim of this study was to compare the prevalence of autoimmune disorders in IBD patients with and without PSC and to correlate the presence of autoimmune disorders in PSC to outcome and HLA association. METHODS: One hundred nineteen PSC patients were included in the study. Each PSC patient with IBD was matched to a IBD patient without PSC. The presence of autoimmune disorders was carefully evaluated in each group. Moreover, comparisons between PSC patients with and without autoimmune disorders were performed. RESULTS: Twenty-five percent of the PSC patients had at least one autoimmune disorder outside the liver and colon compared to 9% in the IBD group without PSC (p < 0.005). Nine of the PSC patients had two or more autoimmune diseases compared to only one patient in the IBD group (p < 0.02). The PSC patients with and without associated autoimmune disease did not differ in clinical presentation, outcome of PSC or HLA alleles. A significant overrepresentation of DRB1*03 was still present after excluding PSC patients with concomitant autoimmune diseases outside the liver and colon compared to a healthy Swedish control group. CONCLUSIONS: Autoimmune disorders are more frequent among PSC patients compared to IBD patients without liver disease. Associated autoimmune diseases in PSC patients does not influence the outcome or clinical presentation of PSC.

Deinstitutionalization and schizophrenia in Finland II: discharged patients and their psychosocial functioning.

Three representative cohorts of schizophrenia patients deinstitutionalized from psychiatric hospitals in 1982, 1986, and 1990 were followed up for 3 years in Finland. Patients of the last cohort were older, more disturbed, and had been ill for a longer time than those discharged at the beginning of the 1980s. Despite this, the mortality of patients deinstitutionalized in 1990 did not increase, and their psychosocial functioning seemed to become even better during the 3-year follow-up period compared with those deinstitutionalized during the previous decade. Patients who had been discharged in 1990 were more often living alone than those discharged in the 1980s. Homelessness was rare throughout the study period. In general, patients were more satisfied with their life situation at follow-up compared with that on discharge. Furthermore, most patients were satisfied with their treatment situation. Altogether, the psychiatric care system seemed to be able to meet schizophrenia patients' need for care fairly well during the rapid deinstitutionalization process in Finland. More attention, however, should be paid to the loneliness and social withdrawal of discharged patients as well as to other disabilities in their social functioning.

The CTLA-4 gene is associated with multiple sclerosis.

We have investigated whether three intragenic polymorphisms of the CTLA-4 gene, a C/T base exchange in the promoter (p.-318), an A/G substitution in exon 1 (p.49) and a dinucleotide repeat polymorphism in exon 4 (p.642), were associated with genetic susceptibility to multiple sclerosis (MS). We observed a significant association (p < 0.05) for homozygosity for the G49 allele in a case-control analysis of 378 MS patients and 237 controls, and a transmission disequilibrium (p < 0.02) for the G49 allele in 31 MS families. This was further corroborated by evidence for linkage by the affected pedigree member (APM) analysis (p < 0.0002) and a transmission distortion (p < 0.05) of the exon 4(642) polymorphism. Sequencing of the promoter, the first and second exons and the parts of the first intron revealed no further polymorphisms. Our results suggest that a dysregulation of CTLA-4-driven downregulation of T-cell activation could be involved in the pathogenesis of MS.

HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations.

The association of primary sclerosing cholangitis (PSC) to HLA class II genes was studied by comparing patients from five different European populations. Deduced HLA-DRB1, DQA1, DQB1 haplotypes of 256 PSC patients from England, Italy, Norway, Spain and Sweden were compared to those observed in 764 ethnically-matched controls. Increased frequencies of the DRB1*03, DQA1*0501, DQB1*02 (RR=3.0, P<0.00001) and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes (RR=2.4, P<0.0001) were observed in all five patient groups. A total of 16% of the PSC patients were homozygous for the DRB1*03, DQA1*0501, DQB1*02 haplotype compared to 1% of the controls (RR=20, P<0.0001). The DRB1*04, DQA1*03, DQB1*0302 haplotype was significantly reduced in frequency(RR=0.4, P<0.00001). Among Norwegian, Swedish and British patients that did not carry neither the DRB1*03, DQA1*0501, DQB1*02 nor the DRB1*13, DQA1*0103, DQB1*0603 haplotype, an increased frequency of the DRB1*15, DQA1*0102, DQB1*0602 haplotype was observed (RR=2.0, P<0.0001). Thus, PSC was found to be positively associated to three different HLA class II haplotypes (i.e. the DRB1*03, DQA1*0501, DQB1*02, the DRB1*15, DQA1*0102, DQB1*0602 and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes) and negatively associated to one HLA class II haplotype (i.e. the DRB1*04, DQB1*0302 haplotype).

Deinstitutionalization and schizophrenia in Finland: I. Discharged patients and their care.

Finland has experienced one of the most rapid psychiatric deinstitutionalization processes in the world. Since 1980, the use of psychiatric beds has decreased about one-third. The effects of this deinstitutionalization were studied in the national Discharged Schizophrenia Patient Project. The study used three representative samples of patients with schizophrenia who were discharged from mental hospitals in 1982, 1986, and 1990, and followed them for 3 years. Patients with schizophrenia discharged at the beginning of the 1990s were older and more disturbed, and had been ill for a longer time than patients discharged at the beginning of the 1980s. The use of outpatient care increased and that of hospital care decreased, but because of the increased residential outpatient care, the total amount of residential care did not change during the study period. However, readmissions to the hospital increased. In patients with a long duration of illness, the increase in readmissions was exceptionally high; these patients also seemed to be losing their share of the residential outpatient services. On the whole, from the point of view of the psychiatric treatment system, deinstitutionalization seemed to have proceeded fairly successfully. The system proved able to redirect and use the available resources more effectively and to modify the structure of services according to the changing needs of patients discharged from hospitals. The well-developed social services have also supported this adaptation to the decreasing use of mental hospital beds.