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Biomedical subjects

Michel Fournier

Publications and source records attributed to Michel Fournier.

At least 19 recordsLinked to original sources
PubMed2006

Thrombotic microangiopathy with acquired deficiency in ADAMTS 13 activity in lung transplant recipients.

BACKGROUND: Thrombotic microangiopathy may develop after solid organ transplantation, but it is usually not associated with severe deficiency in von Willebrand factor-cleaving metalloprotease (ADAMTS 13) activity. METHODS: We present the cases of two lung transplant recipients who experienced a thrombotic microangiopathy associated with an acquired severe (<5%) deficiency in ADAMTS 13 activity. RESULTS: A major feature of both cases was the occurrence of a diffuse alveolar hemorrhage. CONCLUSION: Our two cases of lung transplant patients, with thrombotic microangiopathy related to an acquired ADAMTS 13 deficiency recipients, confirm that this mechanism may also be involved in the pathogenesis of thrombotic microangiopathy developing after solid organ transplantation. Therefore, we consider that ADAMTS 13 activity should be assessed on a systematic basis in this setting.

ADAM Proteins↗
PubMed2006

Immunomodulatory effects of estradiol and cadmium in adult female rats.

A wide range of toxic effects has been associated with cadmium (Cd) exposure in mammals. However, the physiological factors that modulate these effects have received limited attention. We have previously demonstrated that neonatal exposure of rats to Cd during lactation results in sex-specific immunotoxic effects in both juvenile and adult rats. The objectives of this study were to determine the effects of 17beta-estradiol (E(2)) on the immunotoxicity of Cd in female rats. We compared the effects of 28 days of exposure to 0, 5, and 25 ppm cadmium chloride (CdCl(2)) through drinking water on ovariectomized Sprague-Dawley rats and on ovariectomized rats with E(2) implant which mimicked the physiological level of E(2) in female rat. Our results clarify the control of important immune functions by E(2) at physiological level and demonstrate significant interactions between Cd and E(2) effects on the cytotoxic activity of natural killer cells and phagocytosis of splenic cells as well as on the total number of thymocytes and of the four subpopulations of the thymocytes as defined by the expression of the cell-surface markers CD4 and CD8. Cd and E(2) share several mechanisms of action that may account for these interactions. The estrogenic potential of Cd could also account for some of the observed effects. These interactions have to be taken into consideration in evaluating the risk of Cd immunotoxicity and the possible interactions with hormonal treatments.

Animals↗
PubMed2006

Lung transplantation for pulmonary langerhans' cell histiocytosis: a multicenter analysis.

BACKGROUND: Lung transplantation (LT) may represent a therapeutic option in case of advanced pulmonary Langerhans' cell histiocytosis (PLCH). Little is known however about the characteristics of the patients considered for LT or its results. METHODS: We conducted a retrospective multicenter study by questionnaire on 39 patients who underwent LT for end-stage PLCH at seven centers in France. RESULTS: Of the 39 patients, 15 received single lung transplantation, 15 double lung transplantation and 9 heart-lung transplantation. At evaluation, extrapulmonary involvement was present in 31% of the patients, pulmonary hypertension (PAPm>25 mm Hg) was observed in 92% of cases and was moderate-to-severe (PAPm> or =35 mm Hg) in 72.5%. The survival was 76.9% at 1 year, 63.6% at 2 years, 57.2% at 5 years, and 53.7% at 10 years. Recurrence of the disease occurred in eight cases (20.5%) with no impact on the survival rate. The sole risk factor for recurrence of the disease was the presence of preoperative extrapulmonary involvement. CONCLUSION: Severe pulmonary hypertension is a common feature in patients with end-stage PLCH. Given the good postransplant survival rate and despite a recurrence rate of the disease of approximately 20% after LT, we conclude that LT is a therapeutic option in this setting.

Adolescent↗
PubMed2006

Respiratory complications: a major concern after right hepatectomy in living liver donors.

BACKGROUND: One of the main concerns after living donor liver transplantation is the risk of morbidity and/or mortality that it imposes on the donors. Respiratory postoperative complications in living liver donors have already been reported but their frequency seems to be underestimated. We designed a prospective study to evaluate the rate and the nature of postoperative pulmonary complications in 112 consecutive donors. METHODS: The medical records of the 112 living liver donors operated on at our center from 1998 to 2003 were reviewed and all the cases of respiratory complications were retrieved. Moreover, since 2000, all patients had a computed tomography angiography of the thorax at day 7 on a prospective basis. RESULTS: In all, 112 hepatectomies (44 right and 68 left) for adult-to-adult or adult-to-child liver donation were performed in our center. No postoperative mortality was recorded. Fourteen major respiratory complications developed in of 11 of 112 donors (9.8%), in all cases after right hepatectomy, and included nonsevere pulmonary embolism (n=7), right pleural empyema (n=3), and bacterial pneumonia (n=3). Minor respiratory complications (7.1% of the donors) included iatrogenic pneumothorax (n=3) and pleural effusion requiring thoracocentesis (n=5). Abdominal complications (mainly biliary leak) developed in 10 donors (8.9%), who in the vast majority remained free of pulmonary complications. CONCLUSIONS: In our series, pulmonary complications are frequent in living liver donors. These complications are mainly observed after right hepatectomy. The particular prevalence of pulmonary embolism should lead to focus on its early diagnosis and prevention.

Adolescent↗
PubMed2006

Pulmonary cystic disorder related to light chain deposition disease.

Light chain deposition disease (LCDD) is a rare disorder that very uncommonly affects the lung. We report three cases of severe cystic pulmonary LCDD leading to lung transplantation. Such a presentation has never been previously reported. The three patients present with a progressive obstructive pulmonary pattern associated with numerous cysts diffusely distributed in both lungs. The disease was histologically characterized by non-amyloid amorphous deposits in the alveolar walls, the small airways and the vessels. It was associated with emphysematous-like changes and small airway dilation. Monotypic kappa light chain fixation was demonstrated on the abnormal deposits and along the basement membranes. Electron microscopy revealed coarsely granular electron-dense deposits in the same localizations. Mild extrapulmonary deposits were found in salivary glands in one patient. No immunoproliferative disorder was identified. We conclude that LCDD may primarily affect the lung, present as a pulmonary cystic disorder, and lead to severe respiratory insufficiency.

Adult↗
PubMed2006

Needle aspiration as first-line management of primary spontaneous pneumothorax.

BACKGROUND: Initial management of primary spontaneous pneumothorax (PSP) remains a topic of debate. Recent guidelines recommend needle aspiration as the initial strategy for large PSP, but chest tube drainage is still widely used. METHODS: Over a six-year period, we used needle aspiration in all cases of large PSP at our center to assess this technique's efficacy in real-life clinical practice. Our prospective study in the pulmonary intensive care unit of a 680-bed university hospital included patients with a PSP greater than 20%, as estimated by the Light's index. Needle aspiration, performed after local anesthesia, used a plastic intravenous catheter. If it failed, we performed thoracic drainage. RESULTS: The study included 35 patients. The initial success rate of needle aspiration was 69% (n=24/35), the one-week success rate 63% (n=22/35), and the one-year rate 51% (n=18/35). Tolerance of needle aspiration was good except for transient vagal reaction in four patients. No risk factors (age, body mass index, delay before hospitalization, previous pneumothorax, or Light index at inclusion) predicted initial failure of needle aspiration. CONCLUSION: Our results confirmed that needle aspiration is an attractive therapeutic option for patients with large PSP: success was observed in approximately two thirds of cases.

Adolescent↗
PubMed2006

Hemoptysis in lung transplant recipients: a series of 15 cases.

STUDY OBJECTIVES: Respiratory complications are frequent after lung transplantation (LTx), and many of these complications have the potential to cause hemoptysis. However, surprisingly, only a few isolated cases of hemoptysis have been reported in LTx recipients. Here, we describe a series of patients who underwent LTx at our center who developed hemoptysis during their postoperative course. SETTING: A tertiary care university hospital. RESULTS: Of 197 LTx recipients, hemoptysis developed in 15 over a 16-year period. The pulmonary circulation as well as the systemic circulation were involved in the mechanism of hemoptysis. Six patients had moderate or minimal hemoptysis, while nine patients had life-threatening hemoptysis, which occurred during the first year after LTx in all cases. Active necrotizing ischemic airway injury was present in five of the nine patients with life-threatening hemoptysis. Eight of those nine patients died as a result of hemoptysis. Overall, hemoptysis was the cause of death in 4.5% of patients who underwent LTx at our institution. CONCLUSION: In our series of transplant patients, hemoptysis was not rare and was associated with a high rate of mortality.

Adult↗
PubMed2005

Hepatocyte and keratinocyte growth factors and their receptors in human lung emphysema.

BACKGROUND: Hepatocyte and keratinocyte growth factors are key growth factors in the process of alveolar repair. We hypothesized that excessive alveolar destruction observed in lung emphysema involves impaired expression of hepatocyte and keratinocyte growth factors or their respective receptors, c-met and keratinocyte growth factor receptor. The aim of our study was to compare the expression of hepatocyte and keratinocyte growth factors and their receptors in lung samples from 3 groups of patients: emphysema; smokers without emphysema and non-smokers without emphysema. METHODS: Hepatocyte and keratinocyte growth factor proteins were analysed by immunoassay and western blot; mRNA expression was measured by real time quantitative polymerase chain reaction. RESULTS: Hepatocyte and keratinocyte growth factors, c-met and keratinocyte growth factor receptor mRNA levels were similar in emphysema and non-emphysema patients. Hepatocyte growth factor mRNA correlated negatively with FEV1 and the FEV1/FVC ratio both in emphysema patients and in smokers with or without emphysema. Hepatocyte and keratinocyte growth factor protein concentrations were similar in all patients' groups. CONCLUSION: The expression of hepatocyte and keratinocyte growth factors and their receptors is preserved in patients with lung emphysema as compared to patients without emphysema. Hepatocyte growth factor mRNA correlates with the severity of airflow obstruction in smokers.

Aged↗
PubMed2005

Moving forward in fall prevention: an intervention to improve balance among older adults in real-world settings.

OBJECTIVES: We investigated the effectiveness of a group-based exercise intervention to improve balancing ability among older adults delivered in natural settings by staff in local community organizations. METHODS: The main component of the intervention consisted of biweekly group-based exercise sessions conducted over 12 weeks by a professional, coupled with home-based exercises. In a quasiexperimental design, 10 community organizations working with older adults offered the intervention to groups of 5 to 15 persons concerned about falls, while 7 organizations recruited similar groups to participate in the control arm of the study. Participants (98 experimental and 102 control) underwent balance assessments by a physiotherapist at registration and 3 months later. RESULTS: Eighty-nine percent of participants attended the 3-month measurement session (n=177). A linear regression analysis showed that after adjusting for baseline levels of balance and demographic and health characteristics, the intervention significantly improved static balance and mobility. CONCLUSION: Structured, group-based exercise programs offered by community organizations in natural settings can successfully increase balancing ability among community-dwelling older adults concerned about falls.

Accidental Falls↗
PubMed2005

Sex-specific effects of neonatal exposures to low levels of cadmium through maternal milk on development and immune functions of juvenile and adult rats.

Cadmium (Cd) is a major environmental contaminant. Although immunotoxic effects have been associated with Cd exposure, the inconsistency of experimental results underlines the need of an experimental approach more closely related to environmental conditions. We investigated the effects of exposing neonatal Sprague-Dawley rats to environmentally relevant doses of Cd through maternal milk. Dams received 10 parts per billion (ppb) or 5 parts per million (ppm) Cd chloride (CdCl2) in drinking water from parturition until the weaning of the pups. Half of the offspring was sampled at weaning time. The remaining juvenile rats received water without addition of Cd until adulthood. Cd accumulation in kidneys of juvenile rats fed from dams exposed to Cd indicated the transfer of the metal from mother to pups through maternal milk. This neonatal exposure resulted in decreased body, kidney and spleen weights of just weaned females but not of males. This effect was more pronounced in the less exposed females fed from dams exposed to 10 ppb Cd, which also displayed lower hepatic metallothionein-1 (MT-1) mRNA levels. The effect of Cd exposure on body and organ weights did not persist to adulthood. In contrast, we observed gender-specific effects of neonatal Cd exposure on the cytotoxic activity of splenic NK-cells of both juvenile and adult rats. Cd also strongly inhibited the proliferative response of Con A-stimulated thymocytes in both male and female adult rats 5 weeks after the cessation of Cd exposure. These immunotoxic effects were observed at doses much lower than those reported to produce similar effects when exposure occurred during adulthood. In conclusion, neonatal exposures to environmentally relevant levels of Cd through maternal milk represent a critical hazard liable to lead to both transitory and persistent immunotoxic effects.

Animals↗
PubMed2005

Age-specific immunocompetence of the earthworm Eisenia andrei: exposure to methylmercury chloride.

Little information with regard to the sensitivity of the immune system of earthworms to toxicants is currently available. To that effect, we evaluated the yield of coelomocyte immune cells and their phagocytosis potential for four different stages of development of the earthworm Eisenia andrei both for in vitro and in vivo exposure. Cell viability was similar among size classes; extruded cell yield increased from 0.7 x 10(6) cells/worm in the smallest size class to 2.9 x 10(6) cells/worm in the largest size class. The proportion of phagocytically active cells was lower in the smallest groups but not different among the other three groups. Phagocytosis increased incrementally for the first three age/weight groups. The absolute phagocytosis level of the hatchling worms is significantly lower than that of the adult worms. The in vivo filter paper exposure of the mature worms showed a hormetic stimulation of 200-300% of phagocytosis and no significant effects on the phagocytosis potential of the hatchlings. The absolute response of coelomocytes from younger worms was significantly lower and the estimates of lethal mercury concentrations showed the hatchling worms to be roughly three times more sensitive than mature worms.

Age Factors↗
PubMed2005

Analysis of the different histologic lesions observed in transbronchial biopsy for the diagnosis of acute rejection. Clinicopathologic correlations during the first 6 months after lung transplantation.

Acute rejection is an extremely common complication of lung transplantation. (1) To appreciate the interobserver variation in the interpretation of histologic findings and (2) to assess the efficacy of transbronchial biopsy (TBB) for acute rejection diagnosis and associated diseases, particularly infection, we performed a retrospective study including 53 consecutive patients who underwent at least one clinically indicated TBB during the first 6 months after lung transplantation. A total of 94 TBB was obtained. The following histologic features observed in TBB specimens-perivascular mononuclear infiltrates, lymphocytic bronchitis/bronchiolitis, and alveolar lesions, were reliably reproduced by 2 pathologists from the same transplant center, with kappa values ranging from 0.79 to 0.82. For identifying perivascular mononuclear infiltrates, discordance between the 2 observers was significantly associated with moderate/severe alveolar lesions. For the diagnosis of acute rejection, perivascular mononuclear infiltrates had a specificity of 96.5%, a positive predictive value of 97.5%, and a sensitivity of 67.7%, whereas lymphocytic bronchitis/bronchiolitis had a specificity of 56.3% and a sensitivity of 19.4%. Interestingly, there was a positive independent correlation between infection and moderate/severe alveolar histologic lesions ( P < .01). In conclusion, the interobserver agreement between experienced pathologists in TBB interpretation is good. Perivascular mononuclear infiltrates remain the cornerstone for acute rejection diagnosis. The presence of moderate/severe alveolar lesions should prompt to search for infection.

Adult↗
PubMed2005

[Lung transplantation in patients with pulmonary fibrosis].

Lung transplantation has been developed over the last fifteen years as a therapeutic option for different forms of advanced-stage lung disease. Idiopathic pulmonary fibrosis is a good indication. For these patients, single lung transplantation is usually preferred, bilateral lung transplantation to a lesser extent. Survival is similar for these two types of transplantation. The post-transplantation survival in patients with pulmonary fibrosis is about 65-70% at one year and 40% at five years. This rate is lower than observed for COPD or cystic fibrosis. If there are no complications, the patient can recover nearly normal lifestyle. Among the different complications, reimplantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.

Graft Survival↗
PubMed2004

[Hemoptysis].

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Adult↗
PubMed2004

Defect of hepatocyte growth factor production by fibroblasts in human pulmonary emphysema.

Pulmonary emphysema results from an excessive degradation of lung parenchyma associated with a failure of alveolar repair. Secretion by pulmonary fibroblasts of hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) is crucial to an effective epithelial repair after lung injury. We hypothesized that abnormal HGF or KGF secretion by pulmonary fibroblasts could play a role in the development of emphysema. We measured in vitro production of HGF and KGF by human fibroblasts cultured from emphysematous and normal lung samples. HGF and KGF production was quantified at basal state and after stimulation. Intracellular content of HGF was lower in emphysema (1.52 pg/mug, range of 0.15-7.40 pg/mug) than in control fibroblasts (14.16 pg/mug, range of 2.50-47.62 pg/mug; P = 0.047). HGF production by emphysema fibroblasts (19.3 pg/mug protein, range of 10.4-39.2 pg/mug) was lower than that of controls at baseline (57.5 pg/mug, range of 20.4-116 pg/mug; P = 0.019) and after stimulation with interleukin-1beta or prostaglandin E(2). Neither retinoic acids (all-trans and 9-cis) nor N-acetylcysteine could reverse this abnormality. KGF production by emphysema fibroblasts (5.3 pg/mug, range of 2.2-9.3 pg/mug) was similar to that of controls at baseline (2.6 pg/mug, range of 1-6.1 pg/mug; P = 0.14) but could not be stimulated with interleukin-1beta. A decreased secretion of HGF by pulmonary fibroblasts could contribute to the insufficient alveolar repair in pulmonary emphysema.

Acetylcysteine↗