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M de Perrot

Publications and source records attributed to M de Perrot.

At least 19 recordsLinked to original sources
PubMed2006

Pre-implantation multiple cytokine mRNA expression analysis of donor lung grafts predicts survival after lung transplantation in humans.

While current donor selection with clinical findings is generally effective, the imprecise nature of the assessment forces clinicians to remain on the conservative side. A reliable biological marker would assist donor selection and would improve donor organ utilization. We collected biopsies from 169 donor lungs before implantation. Expression levels of IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and IL-1beta were measured by quantitative real-time RT-PCR (qRT-PCR). Seventeen cases died within 30 days after transplantation. No donor factor was significantly associated with 30-day mortality. Univariate analysis of the 84 cases for development of the prediction model showed that IL-6, IL-8, TNF-alpha and IL-1beta were risk factors for mortality and IL-10 and IFN-gamma were protective factors. We analyzed the cytokine expression ratios of risk to protective cytokines. A stepwise logistic regression for 30-day mortality demonstrated that a model containing the ratio of IL-6/IL-10 was the most predictive (p = 0.0013). When applied to the remaining 85 cases for validation, the test of model fit was significant (p = 0.039). Using the cytokine ratio, we were able to define three risk groups with striking differences in survival (p = 0.0003). Multi-cytokine analysis of the donor lung graft with qRT-PCR shows significant promise as a strategy to biologically evaluate the donor lung prior to implantation.

Biopsy↗
PubMed2006

Lymphatic vessel density in the neoplastic progression of Barrett's oesophagus to adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma is an aggressive neoplasm with poor prognosis as a result of early lymph node metastasis. AIMS: To measure lymphatic vessel density (LVD) in the neoplastic progression from Barrett's metaplasia to adenocarcinoma and determine whether LVD can predict the risk of cancer. In addition, to correlate LVD with lymph node metastasis and assess whether LVD could be used as a prognostic indicator for outcome or survival. METHODS: LVD and microvascular density (MVD) were assessed after immunohistochemical staining of vessels in Barrett's metaplasia, dysplasia, and adenocarcinoma tissues and were correlated with clinicopathological features. RESULTS: LVD was significantly reduced in adenocarcinoma, being half that seen in normal stomach/oesophagus or metaplasia/dysplasia. LVD did not correlate with tumour grade, stage, or clinical outcome; however, patients who had either lymph node metastasis or invasion of tumour cells into peritumorous lymphatic vessels had a significantly worse overall survival. MVD was also assessed as a prognostic marker; its increase appeared to be linked more with the development of Barrett's metaplasia than adenocarcinoma. CONCLUSIONS: The reduction in lymphatic vessel numbers was not useful for determining disease outcome in the patient group studied. It is the entry of tumour cells into pre-existing peritumorous lymphatic vessels that confers a significantly worse overall survival.

Adenocarcinoma↗
PubMed2006

Epithelioid angiosarcoma of the lung: a rare late complication of Lucite plombage.

Epithelioid angiosarcoma of the lung is a rare late complication of Lucite plombage treatment of pulmonary tuberculosis. We describe the clinical, radiological and pathologic findings of a case of epithelioid angiosarcoma of the lung presenting with persistent haemoptysis who had undergone remote lung collapse therapy with Lucite plombage.

Aged↗
PubMed2005

A randomized, placebo-controlled trial of complement inhibition in ischemia-reperfusion injury after lung transplantation in human beings.

OBJECTIVE: Complement activation has been shown to play a significant role in ischemia-reperfusion injury after lung transplantation. TP-10 (soluble complement receptor 1 inhibitor) inhibits the activation of complement by inactivating C3a and C5a convertases. This was a clinical trial of TP-10 to reduce ischemia-reperfusion injury in lung transplantation. METHODS: In a randomized, double-blinded, multicenter, placebo-controlled trial, 59 patients from four lung transplant programs received TP-10 (10 mg/kg, n = 28) or placebo (n = 31) before reperfusion. This dose achieved 90% complement inhibition for 24 hours, and activity had returned toward normal by 72 hours. RESULTS: At 24 hours, 14 of 28 patients in the TP-10 group (50%) were extubated, whereas only 6 of 31 patients in the placebo group (19%) were (P = .01). The total times on the ventilator and in the intensive care unit both tended to be shorter in the TP-10 group, but these differences did not achieve statistical significance. Among patients requiring cardiopulmonary bypass (n = 5 in placebo group and n = 7 in TP-10 group), the mean duration of mechanical ventilation was reduced by 11 days in the TP-10 group (10.6 +/- 5.0 days vs 21.5 +/- 5.9 days in placebo group, P = .2). Operative deaths, incidences of infection and rejection, and length of hospital stay were not significantly different between the two groups. CONCLUSIONS: Short-term complement inhibition with TP-10 led to early extubation in a significantly higher proportion of lung transplant recipients. The effect of TP-10 was greater among patients undergoing cardiopulmonary bypass, with a large reduction in ventilator days. Complement inhibition thus significantly decreases the duration of mechanical ventilation and could be useful in improving the outcome of lung transplant recipients.

Adolescent↗
PubMed2004

Transbronchial administration of adenoviral-mediated interleukin-10 gene to the donor improves function in a pig lung transplant model.

Interleukin-10 (IL-10) gene transfection of donor lungs prior to transplantation is an attractive strategy to reduce ischemia-reperfusion induced lung injury. However, experimental data with gene therapy in large animal models of lung transplantation are generally lacking. We have developed a simple clinically applicable technique for adenoviral-mediated gene delivery of human IL-10 to the lung of large animals that provides homogenous gene expression after 12-24 h of transfection. Using this technique of gene delivery, we have studied the dynamics of adenoviral gene delivery to the lung in the setting of lung transplantation. Although there is a persistent inflammatory response to the adenoviral vector, we achieved significant expression of human IL-10 in lung tissue before lung retrieval to obviate the deleterious impact of the adenoviral vector on the donor lung. The administration of adenoviral-mediated human IL-10 to the donor lung reduced ischemia-reperfusion injury and improved graft function after lung transplantation in this pig lung transplantation model. Transfection of adenoviral-mediated human IL-10 to the donor lung prevented the release of inflammatory cytokines such as IL-6 in lung tissue and plasma. We have demonstrated that IL-10 gene therapy has significant potential to prevent or treat the inflammatory response associated with ischemia-reperfusion injury in lung transplantation. In the future, IL-10 gene therapy could also be used for immunomodulation or tolerance induction.

Adenoviridae↗
PubMed2004

Chronic thromboembolic pulmonary hypertension.

Pulmonary arterial hypertension is a severe disease that has been ignored for a long time. However, over the past 20 yrs chest physicians, cardiologists and thoracic surgeons have shown increasing interest in this disease because of the development of new therapies, that have improved both the outcome and quality of life of patients, including pulmonary transplantation and prostacyclin therapy. Chronic thromboembolic pulmonary arterial hypertension (CTEPH) can be cured surgically through a complex surgical procedure: the pulmonary thromboendarterectomy. Pulmonary thromboendarterectomy is performed under hypothermia and total circulatory arrest. Due to clinically evident acute-pulmonary embolism episodes being absent in > 50% of patients, the diagnosis of CTEPH can be difficult. Lung scintiscan showing segmental mismatched perfusion defects is the best diagnostic tool to detect CTEPH. Pulmonary angiography confirms the diagnosis and determines the feasibility of endarterectomy according to the location of the disease, proximal versus distal. The technique of angiography must be perfect with the whole arterial tree captured on the same picture for each lung. The lesions must start at the level of the pulmonary artery trunk, or at the level of the lobar arteries, in order to find a plan for the endarterectomy. When the haemodynamic gravity corresponds to the degree of obliteration, pulmonary thromboendarterectomy can be performed with minimal perioperative mortality, providing definitive, excellent functional results in almost all cases.

Chronic Disease↗
PubMed2004

Strategies to increase limited donor resources.

A number of strategies have been advocated to increase the number of lung donors including: 1) improvement in donor resuscitation; 2) better methods of lung preservation; 3) extension of the lung donor selection criteria; 4) development of a living-related lung donor programme; and 5) utilisation of nonheart beating donors. Other strategies such as the split-lung technique and techniques of lung reduction to accommodate large lungs into a small-size recipient have also been used successfully. In this article, each of these strategies have been reviewed and some recommendations are suggested based on the authors' own experience and that of the literature.

Age Factors↗
PubMed2003

Management of lung transplant recipients with bronchogenic carcinoma in the native lung.

Experience with lung transplantation for bronchogenic carcinoma is limited. In our experience, 3 of 6 patients died of recurrent carcinoma within 5 to 35 months after transplantation. Hence, we currently do not support lung transplantation for patients with pre-transplant diagnosis of bronchogenic carcinoma, with the exception of bronchioloalveolar carcinoma (BAC) confined to the lung. Patients with BAC should be staged thoroughly with chest and abdominal computerized tomography, brain magnetic resonance imaging, and bone scan repeated every 3 months while on the waiting list, and should undergo mediastinoscopy at the time of transplantation, with a plan for a backup recipient if metastatic lymph nodes are detected. Proposal for lung transplantation for patients with bronchogenic carcinoma, with the exception of BAC, probably should be performed in the setting of a clinical trial developed with input from the lung transplant community.

Carcinoma, Bronchogenic↗
PubMed2003

Clinical lung transplantation--current status.

Since 1983, lung transplantation has enjoyed increasing success and has become the mainstay of therapy for most end-stage lung diseases. While the first decade of clinical lung transplantation focused on technical details of the transplant procedure, the second decade was characterized by improvements in techniques of lung preservation and in the postoperative management. This review will focus on the recent improvements made in lung preservation and postoperative management.

Forecasting↗
PubMed2001

Prostaglandin E1 protects lung transplants from ischemia-reperfusion injury: a shift from pro- to anti-inflammatory cytokines.

INTRODUCTION: Prostaglandin E1 (PGE1) has been demonstrated to reduce ischemia-reperfusion (IR) injury following lung transplantation. However, the cytoprotective mechanisms remain largely unknown. The purpose of this study was to determine whether the mechanism through which PGE1 improves IR injury is related to the level of apoptosis or the release of inflammatory cytokines. METHODS: In a rat single-lung-transplant model, animals were randomly allocated into four groups of five animals each. Group 1 received normal saline (NS) in the preservation solution and during the 2-hr reperfusion period. Group 2 received NS in the preservation solution and PGE1 during the reperfusion period. Group 3 received PGE1 in the preservation solution and NS during the reperfusion period. Group 4 received PGE1 in the preservation solution and during the reperfusion period. RESULTS: The two groups that received PGE1 during the reperfusion period had a significantly higher partial pressure of oxygen (PaO2), lower wet-dry weight ratio, and lower peak airway pressure at the end of the reperfusion period than did the two groups that received NS. In the two groups that received PGE1 during the reperfusion period, we observed significantly higher levels of interleukin (IL)-10 in the transplanted lung tissue and plasma and significantly lower levels of tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and IL-12 in lung tissue. The levels of IL-4 and macrophage inflammatory protein-2 (MIP-2) were not significantly different between groups. The number of apoptotic cells and the expression of Bcl-2 were not significantly different between groups. CONCLUSIONS: PGE1 does not decrease the amount of apoptosis after reperfusion and does not significantly upregulate Bcl-2. We have demonstrated that PGE1 administered during the reperfusion period reduces IR injury and improves lung function through a mechanism that is likely mediated by a shift between pro- and anti-inflammatory cytokine release.

Alprostadil↗
PubMed2001

In vivo transtracheal adenovirus-mediated transfer of human interleukin-10 gene to donor lungs ameliorates ischemia-reperfusion injury and improves early posttransplant graft function in the rat.

We examined the effect of adenovirus-mediated transtracheal transfer of the human interleukin 10 (hIL-10) gene on lung ischemia-reperfusion (IR) injury, which is the insult due to hypothermic preservation plus graft reperfusion, and posttransplant lung function in Lewis rat lungs. Thirty rats were divided into 6 groups (n = 5). Groups 1 and 4 received 5 x 10(9) PFU of Ad5E1RSVhIL-10, groups 2 and 5 received 5 x 10(9) PFU of Ad5BGL2 ("empty" vector), and groups 3 and 6 received 3% sucrose (diluent). After 24 hr of in vivo transfection, lungs were stored at 4 degrees C (cold ischemic time, CIT) for 6 hr (groups 1-3) or 24 hr (groups 4-6) before transplantation. After 2 hr of reperfusion, lung function was assessed by oxygenation (FIO2, 1.0), airway pressure (AwP), and wet-to-dry (W/D) weight ratios. Rat tumor necrosis factor alpha (rTNF-alpha), interferon gamma (IFN-gamma), IL-10, and hIL-10 were measured in graft tissue and recipient plasma by ELISA and detected by immunohistochemistry (IHC). Partial pressure of oxygen (PaO2) levels in the hIL-10 group (6 hr of CIT) were higher than in empty vector and diluent groups (PaO2, 530 +/- 23 vs. 387 +/- 31 and 439 +/- 27 mmHg, respectively, p < 0.05). IL-10 rats after 24 hr of CIT showed higher PaO2 levels (260 +/- 29 mmHg) than empty vector (96 +/- 24 mmHg) or diluent (133 +/- 10 mmHg) lungs (p < 0.05). AwP and W/D ratios were reduced in hIL10 lungs (p < 0.05) compared with the other groups. rTNF-alpha and INF-gamma were reduced in tissue and plasma in groups 1 and 4 (p < 0.05). rIL-10 was reduced in the tissue of hIL-10 lungs (p < 0.05). IHC showed equal distribution of cytokines in tissue and abundant transgene expression in large and small airway epithelium in hIL-10 lungs.

Adenoviridae↗
PubMed2001

Perioperative medical management and outcome following thymectomy for myasthenia gravis.

PURPOSE: To describe the evolution of the perioperative management of myasthenia gravis (MG) patients undergoing thymectomy and to question the need for systematic postoperative ventilation. CLINICAL FEATURES: We collected data retrospectively from 36 consecutive MG patients who underwent thymectomy over a 21-yr period, via transthoracic, -cervical or -sternal incisions (n=5, n=7, n=24, respectively). From 1980 to 1993, a balanced anesthetic technique (n=24) included various inhalational agents with opiates and myorelaxants (in eight cases); 22 patients were admitted to the intensive care unit (ICU). Since 1994, i.v. propofol was combined with epidural bupivacaine and sufentanil (n=12); all patients were admitted to the postanesthesia care unit. Short-term postoperative ventilation (median time four hours, range from three to 48 hr) was required in eight patients who had longer hospital stay (median stay=12 days, range (8-28) vs five days (4-15) for patients with early extubation, P <0.05) but similar clinical improvement six months after thymectomy. Postoperative ventilatory support was required more frequently when a balanced anesthetic technique was used (odds ratio=4.2 (1.1-9.7), P=0.03) and particularly when myorelaxants were given (odds ratio=13.9 (2.1-89.8), P=0.009). Leventhal's scoring system had low sensitivity (22.2%) and positive predictive values (25%). CONCLUSIONS: Our data show that the severity of MG failed to predict the need for postoperative ventilation. A combined anesthetic technique was a safe and cost-effective alternative to balanced anesthesia as it provided optimal operating conditions and resulted in fewer admissions in ICU and shorter hospital stays.

Adolescent↗
PubMed2001

Long-term survival after multiple resections of a fibrosarcoma involving the lung and chest wall.

We report on the case of a 61-year-old male patient who developed a giant fibrosarcoma involving both the lung and chest wall. This patient underwent three extended resections including the chest wall in each case. Radiotherapy was administered after the last resection, when the tumor was obviously not completely removed. The patient lives a normal life with no signs of recurrence 5 years after his last resection. Multiple extended resections of large and aggressive sarcomas can result in long-term survival, with good quality of life, in adequately selected patients.

Fibrosarcoma↗
PubMed2001

Carcinoma arising in congenital lung cysts.

We report on a patient presenting with a bronchioloalveolar carcinoma fortuitously detected in the wall of a bronchogenic cyst. Evidence suggests that unstable epithelial cells contained within the cyst wall may lead to premalignant proliferation and neoplasia. In the current case, we demonstrated an increased proliferative activity in some areas of the cyst consistent with atypical adenomatous hyperplasia. Hence, we stress the importance of close follow-up of all suspected congenital lung cysts because of their potential malignant degeneration.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Factors influencing improvement and remission rates after thymectomy for myasthenia gravis.

BACKGROUND: Thymectomy has become an accepted option in the treatment of myasthenia gravis (MG). However, the optimal selection of patients for surgery remains controversial. OBJECTIVE: The objective of the study is to define factors influencing improvement and remission rates after thymectomy for MG. METHODS: We retrospectively reviewed our experience in the surgical management of patients with MG over the last 20 years, and analyzed if patient's age, sex, preoperative Osserman Stage, thymic histology, duration of symptoms, or radiological findings influenced outcome. RESULTS: There were 25 women and 10 men. Most of them presented with Osserman stage IIA (n = 12) and stage IIB (n = 17). Hyperplasia of the thymus was observed in 15 patients (43%), thymoma in 12 (34%), and atrophic or normal thymus in 8 (23%). Computed tomography (CT) had a positive predictive value of 91% in detecting thymoma and of 80% in detecting thymic hyperplasia. Over a mean follow-up of 96 months, MG improved markedly in 26 patients. Postoperative improvement was significantly greater in patients with advanced MG (stage IIB, III and IV), whereas a higher rate of remission occurred in patients with mild MG (stage I and IIA), and in those with thymic hyperplasia. No relation was observed between outcome and age, sex, duration of symptoms and abnormal CT findings. CONCLUSIONS: The beneficial effects of thymectomy are characterized by postoperative clinical improvement in most patients with moderate to severe preoperative myasthenic involvement and by a higher remission rate in patients with thymic hyperplasia and/or mild myasthenic symptoms.

Adolescent↗
PubMed2000

Massive cerebral edema after I.V. cyclosporin overdose.

We describe a patient who accidentally received an infusion of cyclosporin at a rate of 30 mg/hr during 13 hr instead of the prescribed dose of 3 mg/hr and who concomitantly developed massive intracerebral edema with brainstem compression and death. A cyclosporin level as high as 1700 ng/ml could have been reached before the drug was withdrawn. To the best of our knowledge, this is the first case of fatal cyclosporin overdose reported in an adult patient.

Brain Edema↗
PubMed2000

[Stage-based management of bronchial carcinoma: the surgeon's point of view].

Surgery is the treatment of choice for non-small cell lung carcinoma (NSCLC) stage I and II. However, adjuvant or neoadjuvant chemotherapy may prove to be of benefit for stages IB and II. Treatment of non-small cell lung carcinoma stage IIIA remains controversial. Recently, neoadjuvant chemotherapy has shown excellent results in patients with metastases to mediastinal lymph nodes discovered at mediastinoscopy and, therefore, seems to be the treatment of choice for these patients. Patients with non-small cell lung carcinoma stage IIIB and IV may benefit from surgery in rare and extremely well selected cases.

Carcinoma, Non-Small-Cell Lung↗