Biomedical subjects
P Rousseau
Publications and source records attributed to P Rousseau.
Ethical and legal issues in palliative care.
As palliative care emerges as a respected and important component of contemporary health care, ethical issues will arise that confront and contest the provision of medical care. The basic principles of medical ethics, embodied in beneficence, nonmaleficence, autonomy, and justice, guide primary care physicians in dealing with dying patients. This article will discuss the basic ethical principles and the principle of double effect, decision-making capacity, advance directives, withholding and withdrawing life-sustaining therapy, futility, artificial nutrition and hydration, do-not-resuscitate orders, and physician-assisted suicide and euthanasia.
Kindness and the end of life.
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Caring for the dying: why is it so hard for physicians?
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"Distraction" of grafted alveolar bone in cleft case using endosseous implant.
OBJECTIVE: Presentation of a specific surgical technique of vertical alveolar ridge distraction performed on an alveolar bone graft 1 year after the primary grafting procedure designed to correct a labioalveolar cleft. The graft had not obtained the results desired and presented heavily scarred mucosal tissue. TECHNIQUE: A dental implant placed within the graft once it has been entirely freed by osteotomies functions as an endless screw. To avoid vascular risk, the alveolar bone graft is detached as a whole along its total height. Consequently, no bone remains above it to provide support for a conventional alveolar distractor. An osteosynthetic miniplate, fastened in a horizontal position beneath the nasal mucosae above the graft, is used to replace the missing bony support and to stabilize the implant, which activates the distraction process. PATIENT: This study is based on our first clinical case with a follow-up of 18 months at present. RESULT: A vertical displacement of the entire graft was achieved, including its attached mucosal layer, which repositioned both bone and mucosa on a far better level in the cleft area. Thus, a normal length of abutment was obtained permitting prosthetic rehabilitation based on the same endosseous implant, which was left in place within the graft. CONCLUSION: This technique may prove particularly helpful in certain cases in which a primary alveolar bone grafting procedure has produced borderline results. In such cases, on the one hand, neither the reasonably satisfactory volume of the bone graft itself nor the poor quality of its scarred mucosal tissue argue in favor of a secondary grafting procedure. On the other hand, it is impossible to resort to currently available alveolar distracters since our choice of techniques leaves no bone support above the graft.
Images in hepatology. Acute cholecystitis revealing a diaphragm disinsertion.
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The X1 box of HLA-G promoter is a target site for RFX and Sp1 factors.
HLA-G gene regulation was investigated with regards to homologies among the pathways regulating both classical MHC class I and MHC class II gene expression. They include four conserved cis-acting regulatory elements located in the proximal promoter region referred to as the W/S/Z box, the X box that is comprised of the X1 and X2 halves, and the Y box with an inverted CCAAT site. The X1 box is the binding site for the ubiquitous RFX complex consisting of three subunits; the X2 box is bound by the X2BP/ATF/CREB family factors. The basic S-X-Y regulatory module interacts with CIITA, which is expressed constitutively in APCs, but may be inducible in others cell types by IFN-gamma. Within HLA-G gene promoter the only conserved motifs are S and X1 boxes. We thus investigated the binding capacity of the HLA-G X box in comparison to that of HLA-DRA and HLA-E. We demonstrate that X2 box mutations in HLA-G promoter affect the binding of ATF/CREB family factors and may privilege the X2 box to access by other shared factors. The X1 box is the target for RFX complex and an additional factor we identified as Sp1. We propose that the X region in the HLA-G gene promoter might participate to the combination of factors which play a role in HLA-G gene activation.
Education and care at the end of life.
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Spirituality and the dying patient.
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The ethical validity and clinical experience of palliative sedation.
The physician's main goal in caring for a dying person is to reduce suffering, including pain, physical symptoms, and emotional, psychosocial, and spiritual distress. In refractory and intractable cases, palliative sedation offers a compassionate and humane alternative to conscious and continual suffering, both for the patient and the patient's family. Without a doubt, further studies are necessary, particularly in cases of cognitive impairment, but palliative sedation offers a valuable and efficacious intervention for interminable suffering at the end of life.
The losses and suffering of terminal illness.
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Conformational changes induced by phosphorylation of the FixJ receiver domain.
BACKGROUND: A variety of bacterial adaptative cellular responses to environmental stimuli are mediated by two-component signal transduction pathways. In these phosphorelay cascades, histidine kinases transphosphorylate a conserved aspartate in the receiver domain, a conserved module in the response regulator superfamily. The main effect of this phosphorylation is to alter the conformation of the response regulator in order to modulate its biological function. The response regulator FixJ displays a typical modular arrangement, with a phosphorylatable N-terminal receiver domain and a C-terminal DNA-binding domain. In the symbiotic bacterium Sinorhizobium meliloti, phosphorylation of this response regulator activates transcription of nitrogen-fixation genes. RESULTS: The crystal structures of the phosphorylated and of the unphosphorylated N-terminal receiver domain of FixJ (FixJN) were solved at 2.3 A and 2.4 A resolution, respectively. They reveal the environment of the phosphoaspartate in the active site and the specific conformational changes leading to activation of the response regulator. Phosphorylation of the conserved aspartate induces major structural changes in the beta 4-alpha 4 loop, and in the signaling surface alpha 4-beta 5 that mediates dimerization of the phosphorylated full-length response regulator. A site-directed mutant at this protein-protein interface decreases the affinity of the phosphorylated response regulator for the fixK promoter tenfold. CONCLUSIONS: The cascade of phosphorylation-induced conformational changes in FixJN illustrates the role of conserved residues in stabilizing the phosphoryl group in the active site, triggering the structural transition and achieving the post-phosphorylation signaling events. We propose that these phosphorylation-induced conformational changes underly the activation of response regulators in general.
A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma.
BACKGROUND: Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. METHODS: Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). RESULTS: With a median follow-up time of 12.2 months (27-65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). CONCLUSIONS: Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases.
Phosphorylation-induced dimerization of the FixJ receiver domain.
The 'two-component' transcriptional activator FixJ controls nitrogen fixation in Sinorhizobium meliloti. Phosphorylation of FixJ induces its dimerization, as evidenced by gel permeation chromatography and equilibrium sedimentation analysis. Phosphorylation-induced dimerization is an intrinsic property of the isolated receiver domain FixJN. Accordingly, chemical phosphorylation of both FixJ and FixJN are second-order reactions with respect to protein concentration. However, the second-order phosphorylation constant is 44-fold higher for FixJN than for FixJ. Therefore, the C-terminal transcriptional activator domain FixJC inhibits the chemical phosphorylation of the receiver domain FixJN. Conversely, FixJN has been shown previously to inhibit FixJC activity approximately 40-fold, reflecting the interaction between FixJN and FixJC. Therefore, we propose that modulation of FixJ activity involves both its dimerization and the disruption of the interface between FixJN and FixJC, resulting in the opening of the protein structure. Alanine scanning mutagenesis of FixJN indicated that the FixJ approximately P dimerization interface involves Val-91 and Lys-95 in helix alpha4. Dimerization was required for high-affinity binding to fixK promoter DNA.
[Plea for accelerated rehabilitation after ligament plasty of the knee by a bone-patellar tendon-bone graft].
Knee rehabilitation after ACL repair with bone-tendon-bone graft is still controversial. While there was a tendency to protect the graft and the donor site in the eighties, actual tendency is to propose more aggressive, so called accelerated rehabilitation protocol. An extensive analysis of the literature shows that this accelerated rehabilitation is justified because of histologic, biomechanic, surgical and clinical arguments. This accelerated rehabilitation is based on seven reasons, at least: 1) the necrosis of the graft, initially observed in animals, does not seem to be as important in humans as demonstrated by histological studies after in vivo biopsies; 2) the use of solid bone-tendon-bone graft, whose resistance is maximum in the early post-operative period and is superior to the resistance of the ACL; 3) the more precise positioning (more "isometric") because of optic magnification allowed by arthroscopy; 4) the absence of graft impingement, routinely controlled, because of a more posterior tibial placement of the graft and the eventual notch-plasty; 5) the solid and confident fixation of the graft because of interference screws; 6) anterior knee pain are less important when early constraints are applied on the knee; 7) finally, undisciplined and demanding patients who refuse all protection for the graft and the donor site, have good and stable results regarding stability of the knees. Early constraints on the knee after bone-tendon-bone graft and interference fixation give better tolerance on the extension mechanism without compromising integrity of the graft and knee stability. Appropriate level of constraints on the ACL graft and the donor site guides the collagenic reorganisation process. Early restoration of normal hyperextension, decreased knee pain and maintenance of muscular trophicity, allowing patients to go back to sport at 4 months, are the most evident benefits of this accelerated rehabilitation. These considerations cannot be applied to the other grafts (fascia lata, semi-tendinous, allografts ...) and to other ways of fixation (sutures, staples, ...).
[Ganglioneuroblastoma in the adult].
BACKGROUND: Ganglioneuroblastoma is commonly observed in children but rarely in adults. Therapy and prognosis are not well defined in adults. CASE REPORT: We report the case of a female adult who developed a ganglioneuroblastoma of the left adrenal gland with liver metastasis. Surgical treatment combined with radio and chemotherapy led to complete remission. DISCUSSION: The outcome in our patient and data reported in the literature suggest that a multidisciplinary approach is necessary and that initial surgical resection should be performed whenever possible. Adjuvant radiotherapy or chemotherapy have been shown to be somewhat effective in children but their true impact in adults remains to be ascertained. Follow-up after resection should include physical examination, assay of adrenal derivatives in plasma and urine and imaging.