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Biomedical subjects

F Gouin

Publications and source records attributed to F Gouin.

At least 19 recordsLinked to original sources
PubMed2006

Zoledronic acid activates the DNA S-phase checkpoint and induces osteosarcoma cell death characterized by apoptosis-inducing factor and endonuclease-G translocation independently of p53 and retinoblastoma status.

The molecular mechanisms responsible for the cellular effects of the nitrogen-containing bisphosphonate zoledronic acid (Zol) were assessed on several osteosarcoma cell lines differing in their p53 and retinoblastoma (Rb) status. Zol inhibited cell proliferation and increased atypical apoptosis. The Zol effects on proliferation were due to cell cycle arrest in S and G2/M phases subsequent to the activation of the intra-S DNA damage checkpoint with an increase in P-ATR, P-chk1, Wee1, and P-cdc2 levels and a decrease in cdc25c, regardless of the p53 and Rb status. In addition, the atypic apoptosis induced by Zol was independent of caspase activation, and it was characterized by nuclear alterations, increased Bax expression, and reduced Bcl-2 level. Furthermore, mitochondrial permeability was up-regulated by Zol independently of p53 in association with the translocation of apoptosis-inducing factor (AIF) and endonuclease-G (EndoG). Zol also disturbed cytoskeletal organization and cell junctions and inhibited cell migration and phosphorylation of focal adhesion kinases. The main difficulty encountered in treating cancer relates to mutations in key genes such as p53, Rb, or proteins affecting caspase signaling carried by many tumor cells. We have demonstrated for the first time that zoledronic acid activated the DNA damage S-phase checkpoint and the mitochondrial pathway via AIF and EndoG translocation, and it inhibited cell proliferation and induced cell death, bypassing these potentials mutations. Therefore, zoledronic acid may be considered as an effective therapeutic agent in clinical trials of osteosarcoma in which mutation for p53 and Rb very often occur, and where current treatment with traditional chemotherapeutic agents is ineffective.

Animals↗
PubMed2006

[Strategies of management of necrotizing soft tissue infections].

Necrotizing soft tissue infections represent a group of rapidly progressive diseases requiring early and repeated debridement, associated with broad spectrum antibiotics. Delay in surgery or inadequate therapy are the main risk factors for death. Most patients need aggressive critical care management and intensive nutritional support. The management of these patients by experimented senior surgeons is mandatory. A plastic surgeon can help debridement in order to preserve possibilities of later myocutaneous or rotational skin flaps. Intravenous immunoglobulins are an efficacious adjunctive therapy for severe group A streptococcal infection.

Anti-Bacterial Agents↗
PubMed2006

[Hip dysplasia and misalignment in patients aged 20-50 years].

Anterior hip pain in young adult (20 to 50) has two main causes: secondary osteo-arthritis on development dysplasia of the hip, and femoro-acetabular impigement (FAI). This symposium had two parts: the first one analyses long-term results of non-prosthetic surgery (283 osteotomies and shelfs at 15 years FU). The second part concerned the different syndromes with acute anterior hip pain, especially due to FAI and to labral tears.In hip dysplasia, 56 shelf operations, 100 proximal femoral varus osteotomies associated or not with a shelf arthroplasty,and 127 Chiari osteotomies were examined with 10 years minimum follow-up. Only 15% of patients were lost at follow-up before 10 years and average follow-up was 15 years. Results were considered as satisfactory when the Merle d'Aubigne rating was 15/18 or more. The 3 main factors of good prognosis were: a complete correction of both femoral and acetabular dysplasia; age at operation under 40; a moderate arthritis (grade I or II according to De Mourgues and Patte). In single acetabular dysplasia with 3 favorable prognosis factors(no coxa valga, age under 40, arthritis 1 or 2), 85% good results were achieved at 15 years. When patients were over 40 at operation, or in arthritis grade over 2, only 55% of good results were observed. Varus osteotomies, associated or not with shelf arthroplasties, achieved also 85% goods results at 15 years when the 3 favorable prognosis factors were present. Similar good results were also obtained by Chiari osteotomy, but this operation was associated with 12% complications, and more that 25% of lasting limping. Therefore, with 85% good results at 15 years (and often over 20 years), non prosthetic surgery performed at 30-35 years, achieved better functional results than total hip arthroplasty, longer lasting, and not jeopardizing any further possibility of prosthetic surgery.As concerns acute anterior pain of the hip, the clinical and imaging patterns of the different syndromes have been precised: femoro-acetabular impigement by cam (or by pincer), labral tears in hip dysplasia. There were distinguished from the other secondary impigements, for example by acetabular malposition due to pelvis anteflexion or by other hip diseases: overuse arthritis, coxa retrorsa, etc. Several examples of typical syndromes were presented to support the recommended imaging techniques. The results of the speakers with different surgical treatments were reported as well as concerns open surgery than arthroscopic treatment (60 cases).

Acetabulum↗
PubMed2005

Phenotypic and functional analysis of lymphocytes infiltrating osteolytic tumors: use as a possible therapeutic approach of osteosarcoma.

BACKGROUND: Osteosarcoma is the most common type of primary bone tumor. The use of aggressive chemotherapy has drastically improved the prognosis of the patients with non-metastatic osteosarcomas, however the prognosis of the patients with metastasis is still very poor. Then, new and more effective treatments for curing osteosarcoma, such as immunotherapy are needed. Tumor-infiltrating lymphocytes (TIL) have been involved in the control of tumor development and already assessed with success for the treatment of several cancers including melanoma. While TIL represent a fascinating therapeutic approach in numerous malignant pathologies, there is few report concerning adult bone-associated tumors including osteosarcoma. METHODS: Human TIL were isolated and characterized (phenotype, lytic activity) from twenty-seven patients with bone-associated tumors (osteosarcoma, Ewing's sarcoma, giant cell tumor, chondrosarcoma, plasmocytoma and bone metastases). Similar experiments were performed using rat osteosarcoma model. RESULTS: While TIL with a main CD4+ profile were easily isolated from most of the tumor samples, only TIL extracted from osteosarcoma were cytotoxic against allogeneic tumor cells. In all cases, TIL lytic activity was significantly higher compared to autologous peripheral blood leukocytes. Similar data were observed in rat osteosarcoma model where TIL were characterized by a main CD4+ profile and high lytic activity against allogeneic and autologous tumor cells. Moreover, rat TIL expansion was not accompanied by refractoriness to further activation stimulus mainly by tumor antigens. CONCLUSION: These results demonstrated that TIL therapy could be a very efficient strategy for the treatment of adult osteosarcoma.

Adolescent↗
PubMed2005

A new experimental rat model of osteosarcoma established by intrafemoral tumor cell inoculation, useful for biology and therapy investigations.

Satisfactory experimental models for preclinical cancer studies must follow several criteria: (1) reproducibility of the method used to induce the tumor and (2) clinical, pathological and kinetic similarity with the corresponding human tumors. We developed a model of osteosarcoma locally induced by the intrafemoral injection of osteosarcoma (OSR) cells in Sprague-Dawley rats. This method yields nearly 80% of bone tumors at the injection site. These tumors double their volume fairly slowly (in approximately 20 days) and lung metastases occur in 96% of the animals. The OSR cell-induced tumor is characterized by a direct production of mineralized matrix by the tumor cells themselves, as revealed by histochemical analysis. The microarchitectural parameters which were quantified by a microscanner show an increased trabecular bone volume (+238%) when OSR cells were injected in the femur, as compared to controls injected with vehicle. Osteoblastic markers such as alkaline phosphatase, osteopontin, osteocalcin and bone sialoprotein were expressed by the tumor in vivo, whereas the initially injected OSR cells did not express some of these markers, suggesting that OSR cells reacquired an osteoblastic phenotype in a favorable environment. The clinical, radiological and histological data show that this model shares high similarities with the osteocondensing forms of osteosarcoma in humans.

Animals↗
PubMed2005

[Pulmonary arterial hypertension in intensive care unit and operating room].

OBJECTIVE: To review the perioperative anaesthetic management of pulmonary arterial hypertension. DATA SOURCES: Extraction from Pubmed database of French and English articles on the perioperative anaesthetic management of pulmonary hypertension for 9 years. DATA SELECTION: The collected articles were reviewed and selected according their quality and originality. The more recent data were selected. DATA SYNTHESIS: Pulmonary arterial hypertension is classically divided in primary and secondary. Primary pulmonary hypertension (familial and sporadic) is relatively severe and rare. Muscularization of the terminal portion of the pulmonary vascular arterial tree, caused by smooth muscle cell hyperplasia is the first change. Pulmonary arterial hypertension linked with disorders of the respiratory system and hypoxemia or pulmonary venous hypertension including mitral valve disease and chronic left ventricular dysfunction are often associated with high morbidity and mortality. The main consequence of pulmonary hypertension development is the occurrence of right-sided circulatory failure. A better understanding of disease pathophysiology will contribute to the development of new therapies increasing then the prognosis of these patients. The management of primary pulmonary hypertension or secondary pulmonary arterial hypertension is a challenge for the anaesthesiologist because the risk of right ventricular failure is markedly increased.

Anesthesia↗
PubMed2005

[Management of catheter-related infections: factors of decision in treatment].

Whenever a catheter related infection is suspected, two main issues must be addressed: should the catheter be removed and should an empiric antibiotic treatment be prescribed? These questions are still under debate. Some differences are found between French and American guidelines. Main factors leading to decision about these questions are: severity of the sepsis, microorganisms involved and kind of patients we are dealing with.

Catheterization↗
PubMed2005

Enhanced tumor regression and tissue repair when zoledronic acid is combined with ifosfamide in rat osteosarcoma.

The efficacy of zoledronic acid (ZOL), with or without the anticancer drug ifosfamide (IFO), was tested on primary bone tumor growth using a rat-transplantable model of osteosarcoma. The effects on bone remodeling and tumor growth were analyzed by radiography, micro-computed tomography (micro-CT), and histological staining. The in vitro effects of ZOL were studied by proliferation, apoptosis, and cell cycle analyses on the osteosarcoma cells OSRGA compared to rat primary osteoblasts. Treatment with ZOL was effective in preventing the formation of osteolytic lesions that developed in bone sites and in reducing the local tumor growth, as compared to the untreated rats. The combination of ZOL and IFO was more effective than each agent alone in preventing tumor recurrence, improving tissue repair, and increasing bone formation as revealed by the analysis of trabecular architecture. In vitro studies demonstrated that ZOL was more potent against the OSRGA cell line than osteoblasts (with a half-maximal inhibitory effect on proliferation seen at 0.2 and 20 microM, respectively), the ZOL-induced inhibition of OSRGA proliferation being due to cell cycle arrest in S-phase. No effect on OSRGA apoptosis could be observed in vitro, as assessed by Hoechst staining and caspase-1 and -3 activation. In situ cell death was determined by TUNEL staining on tumor tissue sections. No significant difference in TUNEL-positive cells could be observed between ZOL-treated and -untreated rats. This is the first report of the anti-bone resorption and antitumoral activities of zoledronic acid in a rat model of osteosarcoma, and its beneficial association with an antitumoral chemotherapeutic drug in preventing tumor recurrence.

Animals↗
PubMed2005

Perioperative cerebral ischaemia in cardiac surgery and BIS.

A 46-year-old woman was monitored by bispectral index monitoring (BIS) during redo aortic and mitral valve replacement. On release of the aortic cross clamp there was a sudden, severe, unexplained, and sustained fall in the BIS value. Postoperatively, a CT scan was consistent with multiple ischaemic lesions. The lesions were presumed to be due to air embolism. This case suggests that a sudden unexplained and persistent fall in BIS may indicate cerebral ischaemia.

Brain↗
PubMed2004

High concentrations of N-BNP are related to non-infectious severe SIRS associated with cardiovascular dysfunction occurring after off-pump coronary artery surgery.

BACKGROUND: Procalcitonin (PCT) blood concentrations are known to be an appropriate marker of severe systemic inflammatory response syndrome (SIRS) induced by coronary artery surgery with and without cardiopulmonary bypass. Pro-brain natriuretic peptide (N-BNP) is a newly described cardiac hormone considered to be an effective marker of severity and prognosis of acute coronary syndromes and congestive heart failure. We evaluated the perioperative time courses of PCT and N-BNP and investigated their role as early markers of severe SIRS (SIRS with cardiovascular dysfunction) induced by off-pump coronary artery bypass (OPCAB). METHODS: Sixty-three patients were prospectively included. The American College of Chest Physicians Classification was used to diagnose SIRS and organ system failure to define severe SIRS. Serum concentrations of PCT and N-BNP were determined before, during and after surgery. Receiver operating characteristic curves and cut-off values were used to assess the ability of these markers to predict postoperative severe SIRS. RESULTS: SIRS occurred in 25 (39%) patients. Nine of them (14%) showed severe SIRS. Significantly higher serum concentrations of N-BNP and PCT were found in patients with severe SIRS with peak concentrations respectively at 8887 pg ml(-1) (range 2940-29372 pg ml(-1)) for N-BNP and 9.50 ng ml(-1) (range 1-65 ng ml(-1)) for PCT. The area under the curve using N-BNP to detect postoperative severe SIRS was 0.799 before surgery (0.408 for PCT; P<0.01) and 0.824 at the end of surgery (0.762 for PCT; P<0.05). CONCLUSIONS: N-BNP may be an appropriate marker indicating the early development of non-infectious postoperative severe SIRS after OPCAB.

Biomarkers↗
PubMed2004

Increased plasma levels of pro-brain natriuretic peptide in patients with cardiovascular complications following off-pump coronary artery surgery.

OBJECTIVE: To compare N-terminal pro-brain natriuretic peptide (NT-pro-BNP), procalcitonin (PCT), and troponin I (Tn I) concentrations during and after coronary artery surgery in patients with or without cardiovascular complications. DESIGN AND SETTING: Prospective, comparative study of 12 months in the cardiovascular intensive care unit in a university hospital. PATIENTS: 60 adult patients undergoing coronary artery bypass grafting with the off-pump technique. MEASUREMENTS AND RESULTS: Plasma NT-pro-BNP, PCT, and Tn I levels were measured before and immediately after the end of operation and on PODs 1, and 2 and 3. We defined complicated postoperative course as myocardial infarction, cardiogenic shock, arrhythmias, congestive heart failure, and death occurring after the fourth postoperative hour. Receiver operating characteristic (ROC) curve cutoff values were used to assess the ability of the three markers to predict future cardiac events. The area under ROC curve (AUC) using NT-pro-BNP to detect a cardiovascular complicated course was 0.780 at the preoperative time and 0.850 at the end of surgery. A preoperative NT-pro-BNP value of 397 pg/ml had a sensitivity of 76%, specificity of 67%, and accuracy of 74% for predicting a subsequent cardiovascular complication. An immediate postoperative NT-pro-BNP value of 430 pg/ml had a sensitivity of 80%, specificity of 77%, and accuracy of 76%. Patients with preoperative NT-pro-BNP levels less than 275 pg/ml had an excellent postoperative prognosis. Other two markers were less appropriate. CONCLUSIONS: NT-pro-BNP levels measured before and immediately after off-pump coronary artery bypass seem to be predictive of postoperative cardiac events.

Aged↗
PubMed2004

[Pulmonary embolism of cement during vertebroplasty].

A 62-year-old woman with severe osteoporosis experienced pulmonary embolism by polymethylmethacrylate after percutaneous vertebroplasty. The patient immediately developed respiratory and cardiac distress, and a computed tomographic scan revealed the presence of cement in the pulmonary circulation. Proper techniques can minimize the risk of pulmonary embolism during percutaneous vertebroplasty: adequate preparation of cement and fluoroscopy during the procedure are recommended.

Bone Cements↗
PubMed2004

[Factors affecting quality of care for elderly subjects undergoing surgery for hip fracture: review of the literature].

Hip fractures are one of the leading causes for admission of elderly subjects to healthcare facilities. Because of population aging, the incidence of hip fractures has increased considerably over the last years and will continue to increase in industrialized countries. Hip fracture in an elderly subject may be life threatening and has a significant functional and social impact not only because of the fracture itself, but also because of the risk of complications related to the patient's health status and the long hospital stay. The purpose of this work was to identify in the published literature professional practices, excepting the surgical procedure, associated with better early and long-term outcome in elderly patients with hip fracture. Questions raised concerning the patient's hospital stay include factors related to the preoperative phase (time to surgery, usefulness of traction), the operation itself (antibiotic prophylaxis, anesthesia technique), and the postoperative phase (prevention of venous thrombosis, malnutrition, episodes of confusion, duration of indwelling bladder catheter, correction of anemia, geriatric care during the stay in the orthopedic ward, early and intense rehabilitation, prevention of recurrence). Among these factors, several appear to be associated with better outcome, including long-term outcome--surgery as early as possible in light of the patient's general status, antibiotic prophylaxis in accordance with standard recommendations (SFAR), prevention of venous thrombosis with low-molecular-weight heparin initiated at admission and associated with elastic contention. Oral nutritional support is probably beneficial and should be proposed for all patients. Particular attention must be given to prevention of confusion in order to reduce the rate of institutionalization. The rythm of rehabilitation exercises should be at least five sessions per week. Finally, there are several methods, which are effective in preventing recurrence, taking into account osteoporosis, risk of falls. Preventive measures should be instituted for all patients undergoing surgery for hip fracture.

Aged↗
PubMed2003

[Perioperative management of ventricular assist devices].

OBJECTIVE: To review the perioperative anaesthetic management of ventricular assist devices. DATA SOURCES: Extraction from Pubmed database of french and english articles on the perioperative anaesthetic management of ventricular assist devices for 15 years. DATA SELECTION: The collected articles were reviewed and selected according to their quality and originality. The more recent data were selected. DATA SYNTHESIS: Cardiac transplantation is an effective treatment for patients in end stage cardiac failure, but the average waiting time of 17 months, associated with the lack of organs (357 out of 832 candidates were transplanted in 1996) results in a high number of deaths in patients awaiting transplantation. The appearance in the 1980's, of the first ventricular assist device (VAD) provided a new possibility for the management of patients with end-stage cardiac failure awaiting transplantation ("bridge to transplant"). The perioperative anaesthetic management of these patients is complex. End stage cardiac failure, poorly responsive to pharmacological interventions, results rapidly in secondary organ dysfunctions. VADs produce a rapid improvement in haemodynamic, renal, hepatic and neuro-endocrine functions over a 2 months period, allowing transplantation to take place under optimal conditions. However VADs are not without complications (1 year mortality of 20%), of which the major are: infections (40%), perioperative haemorrhage (30%) and thrombo-embolic sequelae (30%). A best knowledge of pathophysiology of these complications is necessary to an optimal management of patients with ventricular assist devices.

Anesthesia↗
PubMed2003

[Topical methylprednisolone vs lidocaïne for the prevention of postoperative sore throat].

OBJECTIVE: We assessed the efficacy of topical methylprednisolone or lidocaine for prevention of postoperative sore throat. STUDY DESIGN: Randomised, prospective in single blind study. PATIENTS AND METHODS: Sixty patients ASA 1 or 2 undergoing tracheal intubation for dental surgery received before intubation either topical lidocaine 5% (15 puffs) or aerosolized methylprednisolone (80 mg). Postoperative pain was assessed by the patients using a VAS and a specific scoring system for sore throat, cough and hoarseness. Evaluations were performed immediately after emergence from anaesthesia, 1 h later, at time of the first postoperative drink, at time of the first postoperative meal and 24 h after surgery. RESULTS: Patients receiving methylprednisolone showed slightly better scores for sore throat and cough 1 h after surgery. CONCLUSION: Topical methylprednisolone may therefore be a useful adjuvant in the prevention of sore throat after intubation.

Adult↗