Patterns of prescription of four major antipsychotics: a retrospective study based on medical records of psychiatric inpatients.

PURPOSE: (1) To identify factors associated with the choice among the three atypical antipsychotics available in France (amisulpride, olanzapine, risperidone) and the typical antipsychotic of reference: (haloperidol), (2) to compare psychotropic co-prescription rates according to antipsychotic. METHODS: All antipsychotic prescriptions including at least one of the four antipsychotics (n=421) for all inpatients (n=372) hospitalized 24 hours or more in the 6 months previous to the start of the study were included (2003). Data were obtained from medical records and psychiatrist interviews. Of the prescriptions, 13.3% included amisulpride, 39.4% olanzapine, 27.3% risperidone, and 20.0% haloperidol. Mean dosages were 142 mg (amisulpride), 15 mg (olanzapine), 4.5 mg (risperidone), and 19.5 mg (haloperidol). RESULTS: Differences between antipsychotics were observed in relation to patients' age (younger patients prescribed amisulpride and olanzapine, p=0.04), diagnoses (affective disorders more frequently prescribed olanzapine and risperidone, p=0.005), and mode of hospitalization (admissions under constraint more frequently prescribed haloperidol, p<0.001). Antidepressant and anxiolytic-hypnotic co-prescription rates were lower with haloperidol than with atypicals. Mood-stabilizer co-prescription rates were higher for olanzapine and risperidone than for haloperidol and amisulpride. Anticholinergic co-prescription was higher with haloperidol than with atypicals (p<0.001). CONCLUSIONS: Haloperidol was prescribed to a minority and targeted male patients hospitalized under constraint, using high dosages. Type and rate of co-prescriptions varied considerably between haloperidol and atypicals.

[Opinions of couples on care during medical termination of pregnancy]. / Opinions des couples sur la prise en charge lors d'une interruption médicale de grossesse.

OBJECTIVES: To study the medical care, staff attitudes and patients' satisfaction from the decision to the post-intervention medical visit for termination of pregnancy for fetal abnormalies. PATIENTS AND METHODS: All patients and their spouses having a termination of pregnancy at the "Unite de Medecine Foetale" in Port-Royal Hospital between November 1996 and July 1997 were contacted for the study. A self-administered questionnaire was mailed six to eight weeks after intervention. Forty seven women and 42 men returned a completed questionnaire, the response rates were respectively 68% and 61%. RESULTS: The patients and their spouses rated globally very high their satisfaction about the care received. The delay before intervention, the length and pain of labour were rated less positively. The factors associated with satisfaction were the quality of the relationship with the staff, and of information. Positive feelings about delivery were linked with the consideration and relief of pain. Most respondents mentioned that their physical and psychological state has improved at the moment of the survey but the psychological distress subsisted or has increased in one fourth of the cases. On the whole the answers made within the couples were correlated. CONCLUSION: The positive results should be moderated by the number of non-respondents. In a context of very high rates of satisfaction, psychological distress is still present for one respondent out of four, six to eight weeks after termination of pregnancy for fetal abnormalies.

Binding analysis of 95 HIV gp120 peptides to HLA-DR1101 and -DR0401 evidenced many HLA-class II binding regions on gp120 and suggested several promiscuous regions.

To identify HLA-DR-binding peptides within the human immunodeficiency virus (HIV)-1 proteins. 95 overlapping synthetic peptides representing the entire sequence of gp120-LAI were screened for their capacity to bind to two HLA-DR molecules with distant sequences (DR0401 and DR1101). By using a cell surface competitive binding assay, 56 DR-binding peptides were identified, of which 35 bound to both DR1101 and DR0401. A highly significant concordance was evidenced by statistical analysis between binding of peptides to one and to the other DR molecule, suggesting a high proportion of promiscuity among gp120 peptides, even though no clear sequence pattern accounting for such promiscuity was found. DR-binding peptides were located along the entire gp120 sequence. Yet, the majority of them (42 among 56) were concentrated in seven multiagretopic regions that were arbitrarily defined as regions containing four or more overlapping continuous peptides binding to DR1011 and/or DR0401. A good correlation was found between DR-binding regions or DR-binding peptides defined in this study and promiscuous T helper gp120 epitopes previously described in seropositive individuals. All these results suggest that the identification of multiagretopic DR-binding regions may be a great help for the predicition of protein determinants that have the likelihood of being promiscuous T helper epitopes in humans.

Binding of ALA-substituted analogs of HA306-320 to DR1101, DR1301, and DR0402 molecules: correlation of DR-peptide interactions with recognition by a single TCR.

We tested the hypothesis that a cross-reactive T-cell clone could recognize HA306-320 peptide complexed to autologous HLA-DR1101, and also to allogenic HLA-DR0402 and HLA-DR1301 molecules, because of similar orientations of HA306-320 side chains in the groove of the three DR molecules. To approach peptide orientations in each HLA groove we compared the capacity of Ala-monosubstituted analogs to bind and be presented by DR1101, DR0402, and DR1301. Results indicated that the orientation of HA306-320 in DR1101 was grossly similar to the known orientation of HA307-319 in DR0101. Data suggested many similarities in peptide orientations in DR0402 and DR1301 as well. However, differences in binding were also observed. Ala substitution of Y309 had much less effect on peptide binding to DR1301 and DR0402 than to DR1101 and Ala-substitution of T314 increased affinity for DR1301 but not for DR1101 and DR0402. These alterations of peptide-DR interactions were probably communicated to the upper peptide surface. Indeed, the levels of T-cell clone reactivities against analogs mutated at positions predicted to face the TCR were lower when complexed to allogeneic DR molecules than when complexed to DR1101. Yet these epitopic alterations are likely subtle, since the decreased reactivity of the clone to allogeneic molecules could be compensated by peptide substitution at Y309, predicted to face the MHC.

Molecular basis for degenerate T-cell recognition of one peptide in the context of several DR molecules.

We report the study of one CD4+ T-cell clone that recognizes peptide HA306-320 in the context of autologous DR1101 molecules as well as of allogeneic DR1301, DR0402, DR1501, and DR1601 molecules. This degenerate T-cell recognition is mediated by a single T-cell receptor (TCR) as judged by both TCR-V beta sequencing and cold-target competition assays. Restriction analysis shows that substitutions of DR residues within the third hypervariable region result in a loss of T-cell reactivity, which is restored by additional substitutions in the first and/or second hypervariable regions. Thus, there is no correlation between antigen presentation abilities of the different allelic DR products and the degree of sequence homology between these products. DR residues whose substitution is compatible with T-cell recognition potentially interact with peptides rather than with TCRs by virtue of their location in the floor of the groove or as previously documented for residues of the alpha-helix. Furthermore, antigen presentation by allogeneic DR molecules occurs independently of their affinity for the peptide, as determined in cell surface-binding assays using biotinylated HA306-320. Altogether these data suggest that degenerate T-cell recognition mainly depends on an influence of polymorphic DR residues on the configuration adopted by the peptide in the DR groove so that the epitope is left intact.

Implication of HLA-DR residues at positions 67, 71, and 86 in interaction between HLA-DR11 and peptide HA306-320.

To get further insight into the role of three polymorphic DR residues located in one alpha-helix of the HLA-DR binding groove, we studied how natural substitutions at positions 67, 71, and 86 on DR11 molecules influence MHC binding and/or T cell recognition of peptide HA306-320 and of monosubstituted peptide analogues. Our results show that: 1) Reactivities of all HA306-320-specific T cell clones tested are decreased by DR substitution at position 86 and can even be lowered by additional substitutions at position 71, and at positions 71 plus 67, indicating that these three residues are functionally important. 2) The functional effects of substitutions at positions 67, 71, and/or 86 cannot be explained by a decreased affinity of HA306-320 for the substituted DR11 molecules, as determined in binding assays. 3) More likely, they are explained by modifications of the conformation, orientation, or location of the peptide once bound in the HLA groove, because each individual DR substitution at positions 86, 71, and 67 differentially affects the binding ability of the same panel of 50 monosubstituted analogues. 4) This interpretation is reinforced by the identification of a small set of monosubstituted analogues that can compensate the functional effects of DR substitutions at positions 86, 86 plus 71, or 86 plus 71 plus 67, and thus restore T cell reactivities. All together these results strongly suggest that residues 67, 71, and 86 play a key role in interactions with HA306-320, probably by modifying the way the peptide is bound within the binding groove of HLA-DR11. Using the same DR11.1-restricted clones, we identified putative T cell and DR contact residues of HA306-320 by comparing DR binding and T cell-activating capacity of the peptide analogues. This analysis suggests that: 1) Residues 310, 311, 312, 313, and 316 are putative TCR contacts. 2) Peptide HA306-320 anchors to DR11.1 molecules mainly via residue Y-309, possibly at the vicinity of DR residue 86, whereas peptide residues 315 and 317 constitute minor aggregotopes that would be at the vicinity of DR residues 71 and/or 67. 3) Finally, residues 308, 310, and 314 might also be on the MHC side of the DR-peptide-TCR complex.