The early stage of post-transplant obliterative bronchiolitis (OB) is characterized by an influx of inflammatory cells to the lung, among which neutrophils may play a role in key events. The ...potential for chemokines to induce leukocyte accumulation in the alveolar space was investigated. We assessed whether changes in the chemotactic expression profile could be used as sensitive markers of the onset of OB.
Serial bronchoalveolar lavage (BAL) fluids from 13 stable healthy recipients and 8 patients who developed bronchiolitis obliterans syndrome (BOS) were analyzed longitudinally for concentrations of interleukin-8 (IL-8), chemokines regulated-upon-activation and normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein-1 (MCP-1), soluble intracellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These were assessed by enzyme-linked immunosorbent assay (ELISA).
Significantly elevated percentages of BAL neutrophils and IL-8 levels were found at the pre-clinical stage of BOS, on average 151 ± 164 days and 307 ± 266 days, respectively, before diagnosis of BOS. There was also early upregulation of RANTES and MCP-1 in the BOS group (mean 253 ± 323 and 152 ± 80 days, respectively, before diagnosis of BOS). The level of MCP-1 was consistently higher than that of RANTES until airway obliteration. BAL sICAM-1 and sVCAM-1 levels were not statistically different between the groups.
These data support the belief that RANTES, IL-8 and MCP-1 play a crucial role in the pathogenesis of OB. The results show that relevant increased levels of such chemokines may predict BOS, and suggest that there is potential for some of these markers to be used as early and sensitive markers of the onset of BOS. Longitudinal monitoring of these chemokine signals may contribute to better management of patients at risk for developing OB, at a stage when remodeling can either be reversed or altered.
Drugs affecting the central nervous system form a unique group of products for surveillance because they could be misused, abused or diverted. Considering the characteristics of this behaviour that ...is often concealed, specific post-marketing surveillance systems have been developed to monitor abuse of prescription drugs in some countries. The purpose of this review is to list and to describe post-marketing surveillance systems, according their methodology, in France and in foreign countries. These programs are based on adverse effect notifications, medical or legal consequences of abuse, general or specific population-based survey, professional networks or medication databases. Some programs use simultaneously several information sources. In conclusion, the multifaceted nature, the diversity and the inventiveness of post-marketing surveillance systems reflects the complexity of the abuse issue.
Aims. In France, maintenance programmes for opiate users were adopted later than in other countries. Two maintenance treatments are available: methadone is only delivered in specialized centres while ...high dosage (HD) buprenorphine can be prescribed by all general practitioners and in specialized centres. The aim of this study was to compare the socio‐demographic profiles, the practices and drug consumption patterns of the two groups attending specialized centres.
Methodology. The Oppidum Programme (observation of illegal drugs and misuse of psychotropic medications), a multi‐centric survey, surveys drug‐dependent subjects attending specialized care centres throughout France annually. Data were collected by questionnaire on socio‐demographic variables and drug use during the preceding week.
Results. During October 1998, 46 centres took part in the survey. The methadone group (
n = 424) was older, with a better economic situation; 16% used cocaine regularly. The HD buprenorphine group (
n = 616) consumed more heroin (12% vs. 8%) and engaged in more misuse, such as intravenous use, illicit acquisitions or irregular consumption. These practices were more frequent for patients consuming the drug "outwith protocol" or for patients obtaining the drug from a general practitioner.
Conclusion. Our results suggest that patterns of consumption of methadone and buprenorphine are different in several respects: concomitant use of licit or illicit psychoactive substances, route of administration, and illegal acquisition. They also suggest that the behaviours of maintenance treatment users depend less on the nature of the maintenance drug (methadone or high dosage buprenorphine), than the nature of the delivery and monitoring practices.
Aim. This study presents the OPEMA (Observation des pharmacodépendances en médecine ambulatoire) programme and the main results of its last annual survey (november 2010). Method. Collected data ...concern mainly subjects' sociodemographic situation, their state of health and their current consumption of psychoactive substance. Results. In 2010, 1394 subjects have been included, describing 2 450 consumptions of psychoactive susbtance. Their mean age is 38,2±12,7 years. Eighty-six per cent have a stable accomodation and 52% are in employment. Fifty-six percent of included subjects present a psychiatric comorbidity. Among included subjects, HIV and HVC prevalence is respectively 3% and 20%. Fourty-five percent of included subjects have been using intraveinous route, 6% of whom using it currently. Eighty-two percent consume opiate maintenance treatment and 29% benzodiazepines. Conclusion. The OPEMA programme supplement the french pharmacodependence assessment system with collecting data from general practitioners, and promotes a global knowledge of dependent subjects' state of health.
Ventilator-associated pneumonia (VAP) has been implicitly accused of increasing mortality. However, it is not certain that pneumonia is responsible for death or whether fatal outcome is caused by ...other risk factors for death that exist before the onset of pneumonia. The aim of this study was to evaluate the attributable mortality caused by VAP by performing a matched-paired, case-control study between patients who died and patients who were discharged from the intensive care unit after more than 48 h of mechanical ventilation.
During the study period, 135 consecutive deaths were included in the case group. Case-control matching criteria were as follows: (1) diagnosis on admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II score within 7 points; (6) ventilation of control patients for at least as long as the cases. Precise clinical, radiologic, and microbiologic definitions were used to identify VAP.
Analysis was performed on 108 pairs that were matched with 91% of success. There were 39 patients (36.1%) who developed VAP in each group. Multivariate analysis showed that renal failure, bone marrow failure, and treatment with corticosteroids but not VAP were independent risk factors for death. There was no difference observed between cases and controls concerning the clinical and microbiologic diagnostic criteria for pneumonia.
Ventilator-associated pneumonia does not appear to be an independent risk factor for death.
Objectives: The purpose of this study was to evaluate the risk of lung cancer surgery following induction chemotherapy and/or radiotherapy. Methods: This retrospective study included 69 patients ...treated from January 1990 to January 1998 for a primary lung cancer in whom surgery had been performed after induction treatment. Surgery had not been considered initially for the following reasons: N2 disease (IIIA, n = 25); temporary functional impairment (two stages IB and two stages IIIA (N2), n = 4); and doubtful resectability (stage IIIB (T4), n = 40). The medical regimen resulted in combined radio-chemotherapy in 43 patients who received two to four cycles of chemotherapy (average 2.9±0.8 cycles) and 43±8 Gy (range 20–60 Gy), or chemotherapy alone in 26 patients (3±0.7 cycles). Results: Exploratory thoracotomy was performed in four patients (6%). The in-hospital mortality was 9% (n = 6) from respiratory origin in all cases. There were four re-operations (6%): three for bronchial fistula and one for bleeding. Thirty-five patients (51%) required blood transfusion (4.5±3.8 cell packs). The incidence of early and delayed bronchial fistula after pneumonectomy was 15%. Thirteen patients had a postoperative pneumonia (19%). Conclusions: Surgery for lung cancer after induction chemotherapy and/or radiotherapy is associated with an increased risk. If the mortality seems ‘acceptable’, the morbidity rate, however, is high.
Inhaled nitric oxide (NO) and prone position (PP) are two of the new therapeutics proposed in the setting of acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the ...hemodynamic and respiratory effects of NO and prone position in patients with ARDS. Fourteen patients, sedated, paralyzed, and ventilated using volume-control mode, were prospectively investigated. All patients had a radial artery catheter, a pulmonary artery catheter, and a 3-F fiberoptic thermistor catheter advanced via the femoral artery into the descending aorta. The protocol consisted of seven phases: baseline measurements in supine position, SP (T0); SP + NO (T1); baseline 2 in SP (T2); PP without NO (T3); NO + PP (T4); SP + NO (T5); and PP + NO (T6). Inhaled NO (T1) induced an increase in PO2/FI(O2) (from 128 +/- 44 to 180 +/- 75 mm Hg, p < 0.004). Prone position (T3) resulted in an increase in PO2/FI(O2) (193 +/- 83 mm Hg, p < 0.003 versus T0). The association of NO with PP (T4) resulted in a significant improvement in PO2/FI(O2) (261 +/- 98 mm Hg) when compared with T0, T1, and T3. Analysis of variance showed a significant and additive effect of NO and PP on both PO2/FI(O2) (p < 0.000) and shunt fraction (QS/QT) (p < 0.01). Since the association of NO with PP presents additive effects on oxygenation, this association can be proposed for the treatment of ARDS.
Studies of the effects of tobacco smoke often rely on reported exposure to cigarette smoke, a measure that is subject to bias. We describe here the relationship between parental smoking exposure as ...assessed by urinary cotinine excretion and lung function in children with asthma.
We studied 90 children 4-14 years of age, who reported a confirmed diagnosis or symptoms of asthma. In each child, we assessed baseline pulmonary function (spirometry) and bronchial responsiveness to carbachol stimulation. Urinary cotinine was measured by HPLC with ultraviolet detection.
Urinary cotinine concentrations in the children were significantly correlated (P <0.001) with the number of cigarettes the parents, especially the mothers, smoked. Bronchial responsiveness to carbachol (but not spirometry test results) was correlated (P <0.03) with urinary cotinine in the children.
Passive smoke exposure increases the bronchial responsiveness to carbachol in asthmatic children.
In some patients with acute respiratory distress syndrome, the prone position is able to improve oxygenation, whereas in others it is not. It could be hypothesized that the more opacities that are ...present in dependent regions of the lung when the patient is in the supine position, the better the improvement in oxygenation is observed when the patients are turned prone. Therefore, we conducted a prospective study to identify computed tomographic scan aspects that could accurately predict who will respond to the prone position.
We included 46 patients with acute respiratory distress syndrome (31 responders and 15 nonresponders). Computed tomographic scan was performed in the 6-h period preceding prone position. Blood gas analyses were performed before and at the end of the first 6-h period of prone position.
Arterial oxygen partial pressure/fraction of inspired oxygen increased from 117 +/- 42 (mean +/- SD) in the supine position to 200 +/- 76 mmHg in the prone position (P < 0.001). There were 31 responders and 15 nonresponders. There was a vertebral predominance of the opacities (P < 0.0001). However, there was no difference between responders and nonresponders. When only the amount of consolidated lung located under the heart was evaluated, there was more consolidated tissue under the heart relative to total lung area in nonresponders than in responders (P = 0.01).
There are no distinctive morphologic features in the pattern of lung disease measured by computed tomographic scanning performed with the patient in the supine position that can predict response to the prone position.
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