Dependence and resistance in community mental health care-Negotiations of user participation between staff and users.

WHAT IS KNOWN ON THE SUBJECT?: Implementation of user participation is described as a change from a paternalistic healthcare system to ideals of democratization where users' voices are heard in relational interplays with health professionals. The ideological shift involves a transition from welfare dependency and professional control towards more active service-user roles with associated rights and responsibilities. A collaborative relationship between users and professionals in mental health services is seen as important by both parties. Nevertheless, the health professionals find it challenging in practice to reorient their roles and to find productive ways to cooperate. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This study illuminates how user participation is negotiated and involves multiple and shifting subject positions in the collaboration between users and professionals in community mental health care. By taking different positions, the relationship between users and professionals develops through dynamic interaction. This study challenges understandings of equality and implicit "truths" in user participation by illuminating subtle forms of power and dilemmas that arise in user-professional negotiations. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Instead of denying the appearance of power, it is important to question the execution of power in the interplay between users and professionals. Focusing on the negotiation processes between users and professionals is important for increasing reflection on and improving understanding of the dynamic in collaboration and speech. By focusing on negotiations, power can be used in productive ways in user-professional relationships. ABSTRACT: Introduction Implementation of user participation is considered important in today's mental health care. Research shows, however, that user participation lacks clarity and provokes uncertainty regarding shifting roles. Aim To investigate negotiation of user participation in a microstudy of interplay between users and health professionals in community mental health care. Method This qualitative study is based on semi-structured in-depth interviews, involving ten service users and ten professionals in community mental health care in Norway. The analysis is inspired by Willig's model for Foucauldian discourse analysis. Results The study illuminates the dynamic nature of user participation that arises through negotiation between users' and professionals' positions as change enablers, dependents, resisters, persuaders and knowledge holders. Discussion Discourses of user participation allow for different subject positions in mental health care. User participation also involves government and questions of power, as well as ambitions of change and control. Professionals act in different ways to make and keep users active, participating, enterprising and self-governing, and users respond and take part within the same discursive framework. Implications for practice Awareness of subjects' positions in discourses is important to increase reflection on the dynamic interplay in user-professional collaboration.

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).

The HLA-DQ(alpha 1*0102, beta 1*0602) heterodimer may confer susceptibility to multiple sclerosis in the absence of the HLA-DR(alpha 1*01, beta 1*1501) heterodimer.

The frequencies of DR2, DQ6-related DRB1, DQA1, DQB1 haplotypes were compared in 181 multiple sclerosis patients and 294 controls in Norway. All individuals carried either DR2 or DQ6, i.e., the DQ(alpha 1*0102, beta 1*0602) heterodimer. The DR(alpha 1*01, beta 1*1501) and the DQ(alpha 1*0102, beta 1*0602) heterodimers were carried by 171 of the patients (94%) and 289 (98%) of the controls. Seven of the patients and one of the controls carried the DQ(alpha 1*0102, beta 1*0603) heterodimer together with the DR(alpha 1*01, beta 1*1501) heterodimer. Two patients carried the DQ(alpha 1*0102, beta 1*0602) heterodimer in the absence of the DR( alpha 1*01, beta 1*1501) heterodimer. The DR(alpha 1*01, beta 1*1501) heterodimer was not observed in the absence of the DQ(alpha 1*0102, beta 1*0602) heterodimer or the DQ(alpha 1*0102, beta 1*0603) heterodimer, neither in the patients nor in the controls. Our findings indicate that the genes encoding the DQ(alpha 1*0102, beta 1*0602) heterodimer may confer susceptibility to developing multiple sclerosis in the absence of the DRB1*1501 allele.

Report from the HLA class II typing by PCR-SSP Multicentre Study.

Results from 360 HLA-DR and -DQ 'low-resolution' typings with polymerase chain reaction sequence-specific primers (PCR-SSP), performed by nine laboratories, were analysed for their overall utility in routinely defining the HLA-DR1-DR18, DR51-DR53 and DQ1-DQ9 specificities in less than 2.5 h. Thirty EDTA blood samples and 10 DNA samples were distributed and analysed by each laboratory. DNA was extracted using a rapid bromide salt extraction protocol. Complete HLA-DR and -DQ typings were performed, three by three, on pre-aliquoted 96-tube PCR trays. When compared with reference typing, 351/360 (98%) correct DR typings were obtained, whereas 320/360 (89%) of the DQ phenotypes were correctly assigned. The time for three complete HLA-DR and -DQ 'low-resolution' typings, including DNA extraction, ranged from 2.0 h to 2.3 h. Unfortunately, an unusually high level of PCR amplification failures was observed (3%), probably due to diffusion and a significant volume loss from some of the pre-aliquoted primer mixes. Consequently, only 52% of the typings were without any amplification failure, and 0-2 amplification failures where found in 88% of the PCR-SSP typings performed. The number of HLA-DR-DQ retypings needed was 7 and 8%, respectively, reflecting the low number of typings where allelic identification was directly affected by the relatively high level of amplification failures in this study. Thus, a 91-98% success rate of correctly identified HLA-DR and -DQ alleles could be maintained, even under suboptimal typing conditions.

Dermatitis herpetiformis and celiac disease are both primarily associated with the HLA-DQ (alpha 1*0501, beta 1*02) or the HLA-DQ (alpha 1*03, beta 1*0302) heterodimers.

HLA-DRB1,-DQA1, and -DQB1 genomic typing of 50 patients with dermatitis herpetiformis and of 290 healthy blood donors was performed. Genes encoding the DQ (alpha 1*0501, beta 1*02) heterodimer were carried by 43 (86%) of the patients and 72 (25%) of the controls. Of the remaining seven patients six (12% of all the patients) carried genes encoding the DQ (alpha 1*03, beta 1*0302) heterodimer. These HLA associations are very similar to those observed in patients with celiac disease. We thus conclude that dermatitis herpetiformis and celiac disease are associated to the very same HLA-DQ alpha beta heterodimers.

HLA-encoded genetic predisposition in IDDM: DR4 subtypes may be associated with different degrees of protection.

Recent studies have shown that the risk conferred by the high-risk DQA1*03-DQB1*0302 (DQ8) haplotype is modified by the DRB1*04 allele that is also carried by this haplotype. However, many of these studies suffer from lack of sufficient numbers of DQ-matched control subjects, which are necessary because there is a strong linkage disequilibrium between genes in the HLA complex. In the present study, using a large material of IDDM patients and DQ-matched control subjects, we have addressed the contribution of DR4 subtypes to IDDM susceptibility. Our data, together with recent data from others, clearly demonstrate that some DR4-DQ8 haplotypes are associated with disease susceptibility, while others are associated with protection, depending on the DRB1*04 allele carried by the same haplotype. In particular, our data demonstrate that DRB1*0401 confers a higher risk than DRB1*0404. Based on combined available data on the genetic susceptibility encoded by various DR4-DQ8 haplotypes and the amino acid composition of the involved DRbeta*04 chains as well as the ligand motifs for these DR4 subtypes, we have developed a unifying hypothesis explaining the different risks associated with different DR4-DQ8 haplotypes. We suggest that disease susceptibility is mainly conferred by DQ8 while DR4 subtypes confer different degrees of protection. Some DR4 subtypes (i.e., DRB1*0405, 0402, and 0401) confer little or no protection, while others (i.e., DRB1*0404, 0403, and 0406) cause an increasing degree of protection, possibly by binding a common protective peptide. Features of a protective peptide that fit such a model are briefly discussed.

Serologic subtyping of HLA-DR8 by means of the cytotoxic human monoclonal antibody 5643.

EBV-transformed B cells from a multiparous woman with anti-HLA antibodies were hybridized with CB-F7 heteromyeloma cells. The resulting hybridoma produced the cytotoxic human IgM(kappa) mAb 5643. Testing of the hybridoma supernatant against HLA homozygous cell lines demonstrated positive reactions (titer range 128-512) only with three cell lines that carried the DR (alpha, beta 1*0801) subtype of DR8. There was no reaction with cells expressing other variants of DR8; i.e., carrying the DR beta 1*0802, 0803, or 0804 chains. The only difference between the DR beta 1*0801 and DR beta 1*0802/0804 chains and between the DR beta 1*0801 and 0803 chains is a single aa substitution, a Ser-->Asp substitution at residue 57 and a Phe-->Ile substitution at residue 67, respectively. Residues 57 and 67 are both situated on the alpha-helix of the DR beta chain. The distance between residues 57 and 67 is two full turns of the alpha-helix; i.e., about 1 nm. It is possible that both 57 Ser and 67 Phe are directly involved in the epitope recognition by mAb 5643.

A K-ras 13Gly-->Asp mutation is recognized by HLA-DQ7 restricted T cells in a patient with colorectal cancer. Modifying effect of DQ7 on established cancers harbouring this mutation?

We have characterized and described in detail 2 CD4+ T-lymphocyte clones (TLC) from a colonic cancer patient. These TLC specifically recognize a K-ras-derived peptide carrying the 13Asp mutation commonly found in adenocarcinomas of the colon. The TLC were independently derived, as they carried 2 different T-cell receptors. The TLC recognized partly overlapping epitopes within the 13Asp peptide, presented by HLA-DQ7 molecules, suggesting that this molecule might confer some protective immunity against the mutation. On the basis of analysis of 251 colonic carcinomas, the presence of HLA-DQ7 did not seem to protect against the establishment of carcinomas carrying the 13Asp mutation, since the frequency of the DQ7 haplotype was not decreased among patients having this mutation. A modifying effect of DQ7 on the development of carcinomas with a 13Asp mutation was, however, observed, resulting in fewer tumours reaching advanced Dukes stages when DQ7 was present.

No association of multiple sclerosis to alleles at the TAP2 locus.

MS is associated with genes in the HLA complex. We have previously proposed that the primary HLA-associated susceptibility may be conferred by particular DQ alleles. Furthermore, we have previously found that there is no association of MS to DP alleles. This study shows that MS is not associated to alleles of the TAP2 locus, which is located close to DQ on its centromeric side. This observation provides further support to the notion that HLA-associated susceptibility to MS maps telomeric to the TAP2 locus.

HLA matching of unrelated bone marrow transplant pairs: direct sequencing of in vitro amplified HLA-DRB1 and -DQB1 genes using magnetic beads as solid support.

Sequencing of HLA genes can offer complete information on the HLA class II genes relevant for the outcome of bone marrow transplantation (BMT). Genomic HLA matching of unrelated BMT patient/donor pairs is often based on PCR-SSO typing of HLA class II alleles. Typing a small number of samples by this approach is both expensive and time-consuming, due to the large number of SSO probes required to perform a complete class II typing. Moreover, only polymorphisms explicitly tested for will be found. We now provide the first report of the use of direct sequencing of HLA-DRB1 and -DQB1 genes, using PCR-amplified genomic DNA attached to magnetic beads, for clinical routine HLA matching. Sequencing ladders obtained by this procedure are easily readable, the patterns can be interpreted in HLA homozygous as well as heterozygous individuals, and sequence differences or similarities between the BMT donor and recipient can be directly identified. This genomic typing method is informative, relatively fast and therefore well-suited for the small number of samples usually analyzed in matching of BMT pairs. Furthermore, this technique has the potential for automation.