Pain after total hip arthroplasty: a psychiatric point of view.

After total hip arthroplasty (THA), many studies report that a small percentage of patients mention painful symptoms, whose origin remains more or less obscure. We investigated 1,000 patients who had undergone a THA at least one year before their inclusion in the survey protocol. Among these 1,000 patients, 64 were complaining of pain in the region of the operated hip. These were later examined and investigated, both clinically (physical and psychiatric examination) and paraclinically (radiography, biology). Those requiring it received adequate treatment and the others were only regularly followed up. We identified the cause of all but one patient's pain. In all cases except one, the symptoms of pain without physical cause had a psychiatric origin. The results of our study show that, if the clinical picture is not perfectly clear, a psychiatric screening before surgery could contribute to decreasing the incidence of pain syndrome after THA.

[Psychopathological factors of surgical biopsy within the scope of bone tumors]. / Incidences psychopathologiques de la biopsie chirurgicale dans le cadre des tumeurs osseuses.

Some particularities of cancerous conditions in bone surgery have profound psychological implications for the patients involved: their angst of death is compounded by the fear of mutilation or physical impairment. All medical treatment is undertaken to save the patient's life, but at what cost? The reactions of some patients at different stages of the process, before the diagnosis is established--during a brief stay at the hospital, when biopsy is performed--, when the diagnosis is disclosed and later, during the period of treatment, affect the medical team and are apt to seriously undermine the relationship between doctors and patients. The emergence of a tumor is a major event in a patient's life, even if this tumor eventually turns out to be of the non-malicious kind. Psychological counseling and even the prescription of psychotropic medication may prove necessary: the patient must be helped to cope with a newly acquired sense of powerlessness and the awareness of his or her own mortality. At every step of this personal experience, whether before, during or after the performance of the biopsy, the patient is likely to need help to cope with a sense of anxiety, uncertainty, loneliness, or the consequences of a brutal disclosure of his or her medical condition. Some psychic reactions may take us by surprise. In the first place, we have been puzzled by the discrepancy between the simplicity of the biopsy in operative, surgical terms and the highly emotional reaction it elicited among some patients. To the surgeon, biopsy often amounts to a quick surgical gesture. During their brief stay at the hospital, patients whose condition commands no particular attention are likely to suffer a sense of loneliness while they expect the verdict of the biopsy, and these emotions may be harder to cope with than the implications of serious surgery, should the preliminary analysis require it. Even if it turns out that surgery is not necessary, the anxiety just won't go away and a reactive depression may settle in, oddly enough, one could think. Occasionally, some patients may become aggressive in their dealings with the surgeon, who must remain calm and amenable to have them accept the terms of the treatment. Once the treatment options are reviewed (most of which are stereotypical and codified, a fact that is barely belied by the detailed explanations patiently provided by the medical staff), the patient is left alone to ponder the course and the meaning of life. At this point, life cannot go on under the best possible terms if patients are not offered the opportunity to discuss their physical and moral suffering and if no one is there to listen to complaints that transcend the scope their physical condition.

Antigen-induced TCR-CD3 down-modulation does not require CD3delta or CD3gamma cytoplasmic domains, necessary in response to anti-CD3 antibody.

We studied cytotoxic T lymphocyte (CTL) clones expressing cytoplasmic domain-deleted CD3delta and CD3gamma chains. These cells retained efficient antigen-specific cytolysis. Because the cytoplasmic domains of native CD3delta and CD3gamma chains contain a dileucine-based and a tyrosine-based motif thought to be important for receptor endocytosis, we compared TCR-CD3 down-modulation on the CTL clones expressing or not these domains. We found that antigen-induced TCR-CD3 down-modulation was not dependent on either the CD3delta or CD3gamma cytoplasmic domains. This contrasts with phorbol ester- and anti-CD3 mAb (soluble or plastic-coated)-induced TCR-CD3 down-modulation, that are respectively dependent on CD3gamma and on either CD3delta or CD3gamma cytoplasmic domains, suggesting that differences may exist between the mechanisms of TCR-CD3 down-modulation in response to the three stimuli. TCR-CD3 down-modulation in response to antigen was demonstrated by confocal microscopy to be associated with TCRbeta chain internalization, whether CD3delta and CD3gamma were native or truncated. Inhibition by the protein tyrosine kinase inhibitor PP1 of TCR-CD3 down-modulation in response to antigen was also similar whether CD3delta and CD3gamma cytoplasmic domains were present or not. These properties of receptor down-modulation are discussed with respect to the requirements for TCR engagement on antigen-presenting cells.

[Role of subjective clinical aspects through the evaluation of patients' satisfaction with total arthroplasty of the hip]. / Rôle des éléments cliniques subjectifs pour l'évaluation de la satisfaction des patients après arthroplastie totale de la hanche.

The purpose of this study was to detect subjective elements that came into play with the satisfaction of patients that had been undergoing total hip replacement surgery. None of the patients had ever had a psychiatric pathology or undergone orthopedic surgery before. We defined specific questionnaires in order to support this study, based upon a clinical experience very representative of daily practice. In this study, we have also included the summary of clinical notes which highlight one of the present roles of a psychiatrist in a field which is no longer strictly psychiatric disease. Working daily with surgeons gave us access to patients who do not belong to traditional psychiatry but who need carefully selected words and not only a surgical operation in order to become really relieved. This work demonstrated that the standard quality-of-life questionnaires did not allow to evaluate patients' subjective assessments. In order to take into account this subjectivity, it was necessary to combine questionnaires and open-ended interviews. The analysis of the data gathered in this study showed that half of the patients underwent, roughly 3 months after surgery, a period of temporary frustration, although the hip was already in very good condition, according to objective measures. Patients could get out of this temporary period of disappointment--which seemed to be a necessary stage of mourning of their complaint--without any specific treatment. But a good relationship between surgeon and patient was necessary; it helped the patient and the surgeon to escape a duel or a confrontation. For some patients it may have taken as long as one year to enjoy all the benefits of the operation.

Selection of phenotypically distinct NK1.1+ T cells upon antigen expression in the thymus or in the liver.

Unlike the main TCR alphabeta T cell lineage in which deletion occurs at the CD4+ CD8+ double-positive (DP) stage upon TCR engagement by antigen in the thymus, some T cells appear to require such engagement for their selection, either in the thymus or extrathymically. We used a transgenic TCR (tgTCR) model which, as we previously showed, led to selection upon expression of the corresponding antigen H-2Kb (Kb) in the thymus, of tgTCR/CD3(lo) CD4- CD8- double-negative (DN) thymocytes that expressed the NK1.1 marker (NK T cells) (Curnow, S. J., et al., Immunity 1995. 3: 427). We now report that antigen expression on medullary epithelial cells of the thymus failed to select the NK T cells, whereas its expression on thymocytes did, although tgTCR DP thymocyte development was affected under both conditions. Antigen expression on hepatocytes (Alb-Kb mice) did not perturb tgTCR DP thymocyte development. No enrichment in tgTCR NK T cells was detected in the periphery, except for the liver of the Alb-Kb/tgTCR mice. When reconstitution of thymectomized and irradiated H-2k hosts expressing or not Kb was performed with bone marrow from tgTCR H-2k mice, an enrichment in tgTCR+ NK T cells was found in the liver, but not in the spleen, of the hosts which expressed Kb, either selectively on hepatocytes or ubiquitously. Surprisingly, the majority of the hepatic tgTCR+ NK T cells also expressed the CD8 alpha/beta heterodimer. These results indicate that thymus-independent NK T cells with unique phenotypic characteristics can be selected upon antigen encounter in the liver.

Survey of patient satisfaction after total arthroplasty of the hip.

We have carried out a prospective study based on a series of interviews and written questionnaires completed by 45 patients who underwent surgery, in an effort to evaluate subjective patient satisfaction while recovering from total hip arthroplasty. These patients all had operation for primary osteoarthrosis and none had previously experienced orthopaedic procedures or psychiatric pathology. Our study demonstrated that using standard quality-of-life questionnaires to evaluate patient's subjective assessments is difficult, if not impossible. It also established the need to combine questionnaires and open-ended interviews in order to reveal subjective elements that should be taken into consideration by the surgeon before deciding upon the need to operate. The analysis of the data collected in this study highlights the fact that 50% of the patients express feelings of frustration during a three month-long period following the operation, in spite of their experiencing actual improvements of the operated hip. This phase of temporary frustration winds down easily but it is only a year after undergoing arthroplasty that some patients will enjoy all the subjective benefits of the operation.

Role of CD3gamma and CD3delta cytoplasmic domains in cytolytic T lymphocyte functions and TCR/CD3 down-modulation.

TCR engagement leads to down-modulation of TCR/CD3 complexes from the T cell surface. The importance of this effect in T cell physiology is unknown. Here, we characterized a CTL clone deficient in TCR/CD3 surface expression that had lost both CD3delta and CD3gamma mRNA, allowing us to address the role of these chains in the assembly, signaling, and dynamics of the TCR/CD3 complex. Expression of either CD3delta or CD3gamma alone failed to reconstitute surface expression of the TCR/CD3 complex, but reconstitution with a cytoplasmically truncated CD3delta (delta t) and a native (gamma) or cytoplasmically truncated (gamma t) human CD3gamma led to reexpression of TCR/CD3 complexes in both cases. This indicated that CD3delta and CD3gamma assume specific functions in TCR/CD3 assembly independently of their cytoplasmic domains. The delta t gamma t variant specifically killed target cells, expressed the IFN-gamma gene in response to Ag, and produced TNF-alpha in response to anti-CD3 mAb, but it was affected in CD3 ligand-induced TCR/CD3 down-modulation. Both PMA- and CD3 ligand-induced TCR/CD3 down-modulation were defective in the delta t gamma t variant, whereas the delta t gamma variants were unaffected, and previously described delta gamma t variants were affected only in PMA-induced down-modulation. Specific protein kinase C (PKC) inhibitors indicated that PMA- but not CD3 ligand-induced down-modulation was dependent on PKC activity. Thus, amino acid sequences present in either the CD3delta or CD3gamma cytoplasmic domain control ligand-induced TCR/CD3 down-modulation, and neither these sequences nor this property are required for cytolysis and IFN-gamma gene expression in response to Ag.

Tyrosine and serine protein kinase activities associated with ligand-induced internalized TCR/CD3 complexes.

Ligand engagement of the TCR/CD3 complex leads to its internalization and modulation from the cell surface. In the present study, we analyzed the intracellular fate of internalized TCR/CD3 complexes following activation of a CTL clone with an anti-clonotypic mAb (anti-TCR mAb). Confocal microscopy using fluorescent anti-TCR mAb showed that after 15 min the TCR/CD3 complex colocalized with the transferrin receptor within endosomes, whereas at later times (2 h) it migrated in late endocytic compartments devoid of transferrin receptor. Using a cell fractionation technique, CD3 components could be detected in early endosomes in the absence of ligand-induced internalization, but were detected in late endosomes only after 2-h anti-TCR-induced internalization. In late endosomes, the internalized TCR/CD3 complex was found to be associated with an active protein kinase, distinct from p56(lck) and p59(fyn), which were mainly present in early endosomes, and ZAP-70, which was only present in the postnuclear supernatant. Phosphoamino acid analysis following an in vitro kinase assay of CD3 immunoprecipitates from early and late endosome fractions showed that the CD3 zeta- and epsilon-chains were phosphorylated exclusively on tyrosine, whereas the CD3 gamma- and delta-chains were phosphorylated on serine and tyrosine, as were 40-kDa and 60-kDa associated proteins. Furthermore, the serine phosphorylation was increased in late endosomes compared with early endosomes. These results suggest that the TCR/CD3 may be associated with different kinase activities during its intracellular pathway following ligand triggering.

[Ethics of research in psychiatry. Comparison of France and the United States]. / Ethique de la recherche en psychiatrie. Comparaison France - Etats-Unis d'Amérique.

This article presents a comparison of research ethics in psychopharmacology in France and the United States. The authors present some elements of definition, etymology and of history. In addition, they study how this very specific research is actually done. Many questions are discussed, including the right of the patient, and the problem of normal volunteers. Other aspects are more technical i.e. remuneration, protocol, and the product. Finally the role of the ethics committees is investigated. These committees comprise the third component of the trial that consists of the research and the subject.