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Biomedical subjects

G Simonneau

Publications and source records attributed to G Simonneau.

At least 127 records · Page 7Linked to original sources
PubMed1994

Nebulized versus intravenous albuterol in hypercapnic acute asthma. A multicenter, double-blind, randomized study.

In a multicenter, randomized, double-blind study, we compared the effects of nebulized (5 mg x 2) and intravenous (0.5 mg) albuterol (salbutamol) over 1 h in 47 patients admitted to hospital with severe acute asthma defined as a peak expiratory flow (PEF) below 150 L/min and hypercapnia (Pa(CO2) > or = 40 mm Hg). Additional treatment included nasal oxygen and hydrocortisone succinate. The efficacy was assessed after 1 h. In the group treated by nebulization (NEB group, n = 22) 19 (86%) patients (95% confidence interval: 65 to 97%) had been treated successfully according to predefined criteria, versus 12 (48%) patients (95% confidence interval: 28 to 69%) in the intravenously treated group (i.v. group, n = 25), p = 0.006. The mean increase in PEF was greater in the NEB group than in the i.v. group (+107 +/- 94 L/min versus +42 +/- 66 L/min, p = 0.01) as well as the decrease in Pa(CO2) values (-10 +/- 5 mm Hg versus -2 +/- 12 mm Hg, p < 0.01). Beta agonist-induced hypokalemia was more pronounced in the i.v. group than in the NEB group. We conclude that, in hypercapnic acute asthma, the nebulized route has a greater efficacy and fewer side effects than the intravenous route.

Acute Disease↗
PubMed1994

Soluble TNF receptors (TNF-sR55 and TNF-sR75) in lung allograft recipients displaying cytomegalovirus pneumonitis.

Two distinct types of tumor necrosis factor receptors (TNF-R) have been identified (TNF-R55 and TNF-R75). Both TNF-R also exist in soluble forms (TNF-sR), resulting from the release of the extracellular domains (TNF-sR55 and TNF-sR75). TNF-sR may play an important role in vivo as they can bind to TNF alpha and prevent ligand binding to the cellular TNF-R, thus acting as naturally occurring inhibitors of TNF alpha. Sera from lung allograft recipients with cytomegalovirus (CMV) pneumonitis (12 patients) were assayed for TNF-sR55 and TNF-sR75. The concentrations were compared with those from either control lung recipients displaying neither rejection nor infection (12 patients), or lung recipients with allograft rejection (12 patients). Serum TNF-sR55 and TNF-sR75 concentrations were measured by enzyme-linked immunologic binding assay. Serum TNF-sR55 and TNF-sR75 concentrations were significantly higher during CMV pneumonitis (mean +/- SEM: 13.7 +/- 4.7 ng/ml, and 11.7 +/- 2.7 ng/ml, respectively) than during allograft rejection (3.7 +/- 0.3 ng/ml, p < 0.001, and 2.6 +/- 0.6 ng/ml, p < 0.001, respectively). They were also higher than in control subjects (3.6 +/- 0.3 ng/ml, p < 0.001, and 1.9 +/- 0.5 ng/ml, p < 0.001, respectively). Serum TNF alpha concentration was low in case of rejection or in control subjects (< 20 pg/ml). Conversely increased levels of TNF alpha were detected in the serum of six out of the 12 patients with CMV pneumonitis (p < 0.03 versus rejection and control subjects). Ganciclovir treatment of CMV pneumonitis led to a dramatic decrease of TNF alpha, TNF-sR55, and TNF-sR75 serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Hemodynamic effects of bolus vs 2-h infusion of alteplase in acute massive pulmonary embolism. A randomized controlled multicenter trial.

Four centers participated in a double-blind study in which 53 patients with angiographically documented acute massive pulmonary embolism (baseline Miller index > or = 17/34 and mean pulmonary artery pressure > or = 20 mm Hg) were randomly assigned to treatment with either 0.6 mg/kg bolus injection of alteplase over 15 min with a maximum dose of 50 mg (bolus group; n = 36), or 100 mg of alteplase over 2 h (2-h group; n = 17). The primary objective was to compare the rapidity of resolution of pulmonary embolism as judged by the change in total pulmonary resistance (TPR) over the initial first hour. Further objectives were to evaluate the changes in TPR over the next 11 h and the degree of lung scan resolution at 20 to 28 h. At 1 h, TPR decreased by 29 +/- 17 percent in the bolus group and by 36 +/- 16 percent in the 2-h group (mean +/- SD; p = 0.19). Continuous monitoring of TPR revealed that this variable improved in both groups without significant intergroup differences over the 12-h study period, although TPR decreased initially faster in the 2-h group. At 20 to 28 h, the absolute improvements in the lung scan perfusion defect were 14 +/- 12 percent in the bolus group compared with 13 +/- 9 percent in the 2-h group, with no significant intergroup differences. Major bleeding occurred in one patient of the 2-h group (6 percent) and in three patients of the bolus group (8 percent) (p > 0.5). Four patients (three from the bolus group and one from the 2-h group) may have experienced recurrent pulmonary embolism during the hospital stay. Neither death nor intracranial bleeding occurred.

Acute Disease↗
PubMed1994

[Pulmonary arterial hypertension of chronic thromboembolic origin; therapeutic indications].

Chronic thromboembolic pulmonary hypertension is a rare complication of acute pulmonary embolism. The therapeutic approach to the disease is addressed, based on a series of 81 patients referred to our department between 1984 and 1993. Medical treatment associates long-term anticoagulant therapy and, in some cases, inferior vena cava interruption. Two surgical procedures are available in selected patients: lung transplantation and pulmonary thrombo-endareterectomy. Lung transplantation has been performed in 8 patients since 1988 with 6 survivors with a maximal follow-up of 5 years. Twelve patients underwent pulmonary thromboendareterectomy with in 9 patients a dramatic functional and haemodynamic improvement. Chronic thromboembolism should be systematically investigated as the cause of pulmonary hypertension considering that in selected cases, curative surgery is possible.

Adult↗
PubMed1994

Double lung transplantation in situs inversus with Kartagener's syndrome. Paris-Sud University Lung Transplant Group.

En bloc double lung transplantation with bilateral bronchial anastomoses was successfully performed in three patients with complete situs inversus and end-stage Kartagener's syndrome. Dextrocardia was not a technical problem for institution of cardiopulmonary bypass, but a large azygos vein draining the systemic venous return was systematically preserved. The major technical difficulty was restoration of airway continuity, because patients with situs inversus have an inverse direction and length of the main stem bronchi. The right and left main bronchi of the recipients were approached in the aortocaval sinus and transected approximately at 1.5 cm from the carina. The donor right main stem bronchus was divided at its origin and the donor left main stem bronchus was divided proximal to the upper lobe takeoff. The different bronchial angulation was not an obstacle, and airway continuity was reestablished twice with an end-to-end anastomosis and once with a telescopic technique. Because of the midline position of the left atrium and pulmonary artery, the anastomoses with the respective recipient's structures were made as in patients with situs solitus. One patient required a right lower lobectomy because the position of the right side of the heart interfered with lobar expansion. One patient died of obliterative bronchiolitis 36 months after the operation. The remaining two are alive and doing well after 48 and 6 months, respectively.

Adult↗
PubMed1993

Treatment of severe venous thrombo-embolism with intravenous Hirudin (HBW 023): an open pilot study.

Recombinant Hirudin (rH) is an anticoagulant agent with a specific antithrombin activity independent of antithrombin III. We report the results of the first open pilot study on the curative treatment of acute venous thrombo-embolism (VTE) with rH (HBW 023) in ten patients. The dose of rH tested was 0.07 mg/kg (i.v. bolus) followed by 0.05 mg kg-1 h-1 (i.v. infusion) for 5 days, without activated partial thromboplastin time (APTT) adjustment. Within the trial, no death, VTE recurrence or major bleeding was observed; lung scan pulmonary vascular obstruction improved from 44 to 37%, whereas the venographic Marder score was unchanged; APTT ratio ranged between 1.2 and 2.8. The dose of rH assessed in this study seems to be safe and efficient in the treatment of acute VTE.

Aged↗
PubMed1993

Subcutaneous low-molecular-weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis.

BACKGROUND: A low-molecular-weight heparin, enoxaparin sodium, has been shown to be effective and safe in preventing deep vein thrombosis both in general surgery and in high-risk orthopedic surgery. We conducted a controlled, randomized trial with enoxaparin in the treatment of established deep vein thrombosis. METHODS: In a multicenter trial, we compared fixed-dose subcutaneous enoxaparin, given twice daily, with adjusted-dose intravenous unfractionated heparin (UFH) given by continuous intravenous infusion for the initial 10 days of treatment of patients with proximal vein thrombosis. The primary efficacy outcome was the change of the size of the thrombus assessed by repeated venograms between day 0 and day 10. The primary analysis of safety was based on the incidence of major bleeding during 10 days of treatment. RESULTS: There were 67 patients in each group. Venographic assessment of clot size evolution between day 0 and day 10 showed a statistically significant superiority (P < .002) of enoxaparin over the reference treatment with UFH. Moreover, the incidence of overall recurrent thromboembolic events during 10 days of treatment was significantly higher (P < .002) in the UFH group (seven of 67) than in the enoxaparin group (one of 67). There were no serious bleeding complications in either group. CONCLUSIONS: Enoxaparin is at least as effective and safe as UFH under the conditions of this study. Moreover, it is more comfortable for patients and less time-consuming for nurses and laboratories. Thus, our study confirmed, with the use of enoxaparin, other observations that low-molecular-weight heparin provides a real therapeutic advance in the treatment of deep vein thrombosis.

Acute Disease↗
PubMed1993

Diaphragm function is not impaired by pneumoperitoneum after laparoscopy.

Open cholecystectomy is known to induce a major restrictive respiratory syndrome. These respiratory disturbances, although of reduced magnitude, still persist after laparoscopic cholecystectomy. To determine the role of pneumoperitoneum per se in the respiratory dysfunction observed after this procedure, seven patients were studied before and 2 hours after laparoscopy. This diagnostic procedure avoids the upper midline incision and the surgical injury of cholecystectomy. Ventilatory performance and diaphragm function were assessed as follows: (1) during quiet tidal breathing by obtaining measurements of esophageal, gastric, and transdiaphragmatic pressures; determining the ratio of gastric pressures to esophageal pressures; and abdomen-rib cage partitioning of tidal volume obtained from two differential linear transformers and (2) during maximal respiratory efforts by obtaining measurements of vital capacity and maximal transdiaphragmatic pressure during Müller's maneuver and a sniff test. Although a large residual pneumoperitoneum (assessed as the maximal height of the suprahepatic space: Hmax = 30.3 +/- 7.8 mm) was observed after laparoscopy, we did not find any change suggestive of diaphragm dysfunction. We thus conclude that postoperative residual pneumoperitoneum per se is unable to explain the diaphragm dysfunction observed after open or laparoscopic cholecystectomy.

Cholecystectomy, Laparoscopic↗
PubMed1993

Frequency of mechanical ventilation and respiratory activity after double lung transplantation.

We investigated the contribution of pulmonary afferent nerve fibers to the control of inspiratory activity in awake humans. Eight double lung transplant outpatients and eight normal subjects were hyperventilated with a mechanical ventilator. Respiratory frequency was increased until no respiratory activity was detectable. Then, by either adding CO2 in the inspired gas or decreasing respiratory frequency, end-tidal PCO2 (PETCO2) was increased until inspiratory activity (i.e. change in inspiratory airway pressure peak and/or time profile) was detected. In normal subjects, PETCO2 threshold for inspiratory muscle recruitment was significantly lower when frequency was decreased than when CO2 was added (31.3 +/- 6.8 Torr vs. 38.2 +/- 8.1 Torr respectively, P < 0.005). This was not the case in the double lung transplant group (31.5 +/- 6.5 Torr vs. 32.9 +/- 5.8 Torr). These findings suggest that pulmonary afferent nerves have an inhibitory effect on inspiratory activity in humans.

Adult↗
PubMed1993

In situ production of interleukin-6 within human lung allografts displaying rejection or cytomegalovirus pneumonia.

Interleukin-6 (IL-6) is a pleiotropic cytokine that is a regulator of inflammation and immunity. As production of IL-6 may be an important mechanism by which local and systemic inflammatory processes are regulated during lung transplantation, we measured this cytokine concentration in the serum and bronchoalveolar lavage fluid (BALF) collected in 27 lung recipients. IL-6 bioactivity was analyzed using a B cell hybridoma proliferation assay (B9 cell line). Three groups of clinical situations were analyzed: control lung recipients, rejections, and CMV pneumonia. Serum IL-6 concentrations (mean +/- SEM) were 24.2 +/- 3.3 U/ml in the 26 control samples. In 20 allograft rejection episodes, the serum IL-6 concentration was higher than in control samples but the difference was not significant (59.3 +/- 20.5 U/ml, P > 0.05). IL-6 serum levels were significantly increased during the 14 CMV pneumonias (61.2 +/- 11.5 U/ml, P < 0.01). In BALF, IL-6 levels were increased during CMV pneumonia (52.4 +/- 21.9 U/ml BALF), and to a lesser extent during rejection events (14.1 +/- 3.7 U/ml BALF), as compared with controls (5.6 +/- 1.6 U/ml BALF, P < 0.005, and P < 0.05, respectively). Similar results were observed when IL-6/albumin and IL-6/urea ratios were determined so as to compensate for possible dilution effects in BALF. IL-6 in BALF was produced in situ during CMV pneumonia as shown by in situ hybridization experiments that revealed a significant number of IL-6 gene-expressing alveolar cells in this condition. IL-6 concentrations in the serum and in the BALF were compared. There was no correlation between serum and BALF IL-6 concentrations, showing that serum IL-6 levels do not accurately reflect intrapulmonary IL-6 levels do not accurately reflect intrapulmonary IL-6 production. Thus IL-6 is produced within lung transplants during CMV pneumonia, and to a lesser extent during allograft rejection.

Adolescent↗
PubMed1993

Primary pulmonary hypertension and fenfluramine use.

Not all the risk factors for primary pulmonary hypertension (PPH) are known. Appetite suppressants, including fenfluramine derivatives, are strongly suspected aetiological agents. In a 5 year retrospective study fenfluramine use was evaluated among patients referred to a medical centre specialising in the management of PPH. Fifteen (20%) of 73 patients with PPH had used fenfluramine: all of them were women and in 10 (67%) there was a close temporal relation between fenfluramine use and the development of exertional dyspnoea. Initial right heart catheterisation in the 15 women showed severe resting pulmonary hypertension (mean (SD)) with pulmonary artery pressure (PAP) 57 (9) mm Hg, cardiac index 2.1 (0.5) l/min/m2, and pulmonary vascular resistance (PVR) 29 (10) U/m2. Short-term epoprostenol infusion produced a significant vasodilator response in 10 patients (mean fall in PVR 24 (15%) compared with control values). Three fenfluramine users with PPH showed spontaneous clinical and haemodynamic improvement 3, 6 and 12 months after drug withdrawal but there was no significant difference in overall survival (transplant recipients excluded) between fenfluramine users and controls. Histological examination of lung tissue from five women who had used fenfluramine and 22 controls, with PPH showed features typical of advanced plexogenic pulmonary arteriopathy in all. These results do not accord with earlier reports that PPH associated with fenfluramine is less severe and has a better outcome. Fenfluramine may be one aetiological agent that can precipitate or hasten the development of PPH. The results of a European case-control study should give new insights into risk factors for PPH and the cause and effect relation with fenfluramine.

Adult↗
PubMed1993

Impairment of bronchial mucociliary clearance in long-term survivors of heart/lung and double-lung transplantation. The Paris-Sud Lung Transplant Group.

The study objective was to investigate bronchial mucociliary clearance after heart/lung and double lung transplantation. Bronchial mucociliary clearance was measured using a noninvasive radioaerosol technique: 99mTc-labeled albumin was aerosolized using a spinning-top generator (mass median aerodynamic diameter, 7.5 mu; geometric standard deviation, 1.5 mu). Radioactivity counts were acquired during 60 min with a gamma camera. A region of interest was drawn over the right lung delineated by a 133Xe lung ventilation image. Bronchial mucociliary clearance was assessed as the percentage of decrease in radioactivity per hour calculated on time-activity curves fitted by a monoexponential model. To exclude patients with acute lung rejection, opportunistic lung infection, and obliterative bronchiolitis, all patients with transplants underwent pulmonary function tests and bronchoscopic examination before clearance measurement. Eight heart/lung and five double-lung nonsmoking transplant patients with normal lung histology were studied 19.3 +/- 4.0 mo after surgery and compared to nine normal nonsmokers. A similar proximal deposition of the aerosol was obtained in patients with transplants and normal subjects; skew values of distribution histograms of aerosol radioactivity counts were 2.1 +/- 0.2 and 1.8 +/- 0.1, respectively, and the ratios between central and peripheral 99mTc radioactivity counts were 2.4 +/- 0.1 and 2.3 +/- 0.2, respectively. No significant difference was observed in bronchial clearance values between patients with heart/lung and double-lung transplants (26.4 +/- 3.0 percent/h vs 35.9 +/- 3.5 percent/h). Conversely, bronchial clearance was significantly lower in transplant recipients (30.0 +/- 2.5 percent/h) than in normal controls (58.7 +/- 6.2 percent/h; p < 0.001). This decreased bronchial clearance can be expected to increase the risk of lung infection in long-term survivors of heart/lung and double-lung transplantation.

Adult↗
PubMed1993

Serum neopterin after lung transplantation.

OBJECTIVE: Neopterin (N), a marker for activated cell-mediated immunity, was assayed in the sera of 44 lung recipients early and late after transplantation. The study was a prospective, blind clinical trial designed to evaluate the following: (1) the daily dynamics of the serum neopterin/creatinine (N/C) ratio during the first 3 weeks after transplantation; (2) the correlation between changes in the serum N/C ratio and episodes of rejection or infection; (3) the correlation between the serum N/C ratio and the concentration of serum soluble interleukin 2 receptor (sIL-2R), a marker of T-cell activation; and (4) the potential value of monitoring the serum N/C ratio during noninvasive long-term follow-up of lung recipients. METHODS: Sera from lung recipients were collected every day or every 2 days for the first 3 weeks after transplantation (22 patients) and before fiberoptic bronchoscopy and routine consultation (44 patients). The N concentrations were determined by radioimmunoassay and sIL-2R levels were measured using a sandwich enzyme immunoassay. RESULTS: Serum N/C is an early and sensitive marker of immune activation in the 21 days following transplantation. The N/C ratios during early rejections (815 +/- 182 mumol/mol) and infections (677 +/- 75 mumol/mol) were higher than those in patients with no complications (160 +/- 32 mumol/mol). In contrast, the N/C ratio did not increase during rejection later after transplantation. More than 3 weeks after transplantation, an increase in the N/C ratio was specifically correlated with infections, mainly those due to cytomegalovirus (CMV) (control subjects, 132 +/- 12 mumol/mol; rejections, 163 +/- 25 mumol/mol; CMV pneumonia, 786 +/- 103 mumol/mol, p < 0.001). The N/C ratio correlated with sIL-2R serum levels (r = 0.625, p < 0.001). CONCLUSIONS: Our results indicate that more than 3 weeks after transplantation, the serum N/C ratio increases only in cases of infection, mostly CMV pneumonia. In contrast, both rejection and infectious complications are associated with an increased N production in the early postoperative period.

Adolescent↗
PubMed1993

[Risk factors for gastroesophageal reflux in chronic asthma].

In order to study risk factors for gastroesophageal reflux (RGO), we have analysed the clinical particulars, the spirometry and the different therapies of chronic asthmatics with and without RGO. RGO has been studied using 24 hour pH manometry in 53 patients suffering from chronic asthma. 70% of these patients had RGO, defined as oesophageal pH below 4, for 4.2% or more of the total time. The only predictive factor for the presence of RGO (log regression) was the dose of theophylline (P is equal to 0.02) whose average dose was higher in cases of RGO (9.1 plus or minus 2.3 mg/kg against 6.3 plus or minus 1.7 mg/kg, P is less than 0.03). Although the severity of the asthma and the spirometric parameters were similar. On the other hand, the severity of RGO, assessed as the percentage of the total time passed with a pH below 4 or correlated (multiple regression) with longevity of the disease (P is equal to 0.02) and the dose of theophylline (P is equal to 0.001). These results suggest that the treatment with theophylline and the duration of the asthma could constitute risk factors for RGO in chronic asthma.

Adolescent↗
PubMed1992

Randomized trial of subcutaneous low-molecular-weight heparin CY 216 (Fraxiparine) compared with intravenous unfractionated heparin in the curative treatment of submassive pulmonary embolism. A dose-ranging study.

BACKGROUND: We compared the efficacy and safety of different dosages of a low-molecular-weight heparin, CY 216 D (Fraxiparine), in the treatment of submassive pulmonary embolism with unfractionated heparin in a prospective, randomized, dose-finding study. METHODS AND RESULTS: The primary outcome was the evolution of pulmonary vascular obstruction. We enrolled 101 patients. Four patient groups were formed: standard heparin by continuous intravenous infusion (group 1) and Fraxiparine subcutaneously 400, 600, and 900 anti-Xa Institute Choay units/kg, respectively (groups 2, 3, and 4). Inclusions were stopped prematurely in groups 3 and 4 because of the incidence of major bleedings. At day 8, the improvement of the pulmonary vascular obstruction and the major bleedings were similar in groups 1 and 2. CONCLUSIONS: The Fraxiparine dosage of 400 anti-Xa Institute Choay units/kg is as effective and safe as unfractionated heparin in the treatment of submassive pulmonary embolism.

Analysis of Variance↗
PubMed1992

Activation of macrophages and cytotoxic cells during cytomegalovirus pneumonia complicating lung transplantations.

The functional status of immune cells within human transplanted lungs was analyzed during cytomegalovirus (CMV) pneumonia complicating lung and heart-lung transplantations. The expression of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) genes is a marker for the activation of macrophages as is that of serine esterase B (SE-B) gene for cytotoxic cells. The levels of expression of these genes by bronchoalveolar lavage (BAL) cells were determined by in situ hybridization. Eight cases of CMV pneumonia were included in this study. BAL cells from either rejection episodes (eight cases) or control transplanted patients experiencing neither infection nor allograft rejection (eight cases) were analyzed in parallel. In the control patients, virtually no cells expressed the IL-1 beta, the IL-6, or the SE-B genes. In contrast, these three genes were all expressed in samples from patients with CMV pneumonia. IL-1 beta gene-expressing cells were abundant in all infected patients (mean +/- SEM: 898 +/- 449 positive cells per 10(4) cells, p less than 0.001, compared with those in control patients). IL-6 gene-expressing cells were less numerous (92 +/- 74 positive cells per 10(4) cells) and present in five of the eight cases of CMV pneumonia. Activated cytotoxic cells were detected in seven of the eight cases of CMV pneumonia (36.5 +/- 19 SE-B gene-expressing cells per 10(4) cells, p less than 0.001). During allograft rejections (eight cases) IL-1 beta gene-expressing cells were present in all but one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Lack of bronchial hyperresponsiveness to methacholine and to isocapnic dry air hyperventilation in heart/lung and double-lung transplant recipients with normal lung histology. The Paris-Sud Lung Transplant Group.

To investigate whether survivors of heart/lung and double-lung transplantations have normal or increased nonspecific bronchial responsiveness, nine heart/lung and four double-lung transplant recipients with normal lung histology underwent methacholine challenge and voluntary isocapnic dry air hyperventilation (VIH) in a randomized order at a mean time of 14.8 +/- 12.1 months after surgery. Transplant recipients were compared with 10 normal subjects and 11 patients with mild asthma. Asthmatic patients had a mean provocative concentration of methacholine inducing a 20% fall (PC20) in FEV1 of 3.4 +/- 3.6 mg/ml (SD). Seventy seven percent of the transplant recipients and 70% of the normal subjects had PC20 superior to 32 mg/ml. The percentage fall from baseline FEV1 after VIH was 12.6 +/- 10.4% in asthmatic patients as compared with 1.9 +/- 2.9% in transplant recipients (p = 0.002) and 0.45 +/- 1.2% in normal subjects (p = 0.001). The decrease in FEV1 after VIH was similar in transplant recipients and normal subjects (p = 0.14). These results show that heart/lung or double-lung transplant recipients with normal lung histology have a normal response to nonspecific bronchial stimulation.

Adult↗