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Biomedical subjects

Charles-Hugo Marquette

Publications and source records attributed to Charles-Hugo Marquette.

14 recordsLinked to original sources

Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors.

BACKGROUND: Diagnosis of pulmonary embolism (PE) is difficult in patients with chronic obstructive pulmonary disease (COPD) and exacerbation. OBJECTIVE: To evaluate PE in patients with COPD and exacerbation of unknown origin and explore factors associated with PE. DESIGN: Prospective cohort study. SETTING: University-affiliated hospital in France. PATIENTS: 211 consecutive patients, all current or former smokers with COPD, who were admitted to the hospital for severe exacerbation of unknown origin and did not require invasive mechanical ventilation. MEASUREMENTS: Spiral computed tomography angiography (CTA) and ultrasonography within 48 hours of admission and assessment of the Geneva score. Patients were classified as PE positive (positive results on CTA or negative results on CTA and positive results on ultrasonography) or PE negative (negative results on CTA and negative results on ultrasonography or negative results on CTA and no recurrence of PE at follow-up 3 months later). RESULTS: 49 of 197 patients (25% [95% CI, 19% to 32%]) met the diagnostic criteria for PE. Clinical factors associated with PE were previous thromboembolic disease (risk ratio, 2.43 [CI, 1.49 to 3.94]), malignant disease (risk ratio, 1.82 [CI, 1.13 to 2.92]), and decrease in PaCO2 of at least 5 mm Hg (risk ratio, 2.10 [CI, 1.23 to 3.58]). A total of 9.2% (CI, 4.7% to 15.9%) of patients with a low-probability Geneva score received a diagnosis of PE. An exploratory analysis suggested that substituting malignant disease for recent surgery in the Geneva score might improve its performance in excluding PE in this sample who were more likely to have malignant disease than to have had recent surgery. However, this improvement seems insufficient to exclude PE with enough certainty to withhold therapy for low-risk patients on the basis of the modified score. LIMITATIONS: This study was done in only 1 center. Patients with COPD requiring invasive mechanical ventilation in the intensive care unit were not included. The upper bound of the 95% CI for the low probability of PE according to the Geneva score is too high to rule out PE. The classification of COPD exacerbation of unknown origin was based on the clinician's assessment, not on a standard evaluation for all patients. CONCLUSION: This study showed a 25% prevalence of PE in patients with COPD hospitalized for severe exacerbation of unknown origin. Three clinical factors are associated with the increased risk for PE. The Geneva score and the modified Geneva score should be prospectively evaluated in patients with COPD.

Aged↗

Management of postintubation tracheobronchial ruptures.

STUDY OBJECTIVES: To determine whether nonoperative management can be applied to iatrogenic postintubation tracheobronchial rupture (TBR). DESIGN: Prospective cohort study. PATIENTS AND INTERVENTIONS: Thirty consecutive patients with TBR complicating intubation between June 1993 and December 2005 entered the study. Patients not receiving mechanical ventilation at time of diagnosis were treated nonsurgically. Patients receiving mechanical ventilation who were judged operable underwent surgical repair, while nonoperable candidates had their TBR bridged by endotracheal tubes. RESULTS: Fifteen patients not requiring mechanical ventilation underwent simple conservative management. TBR length measured 3.85 +/- 1.46 cm (mean +/- SD). Eight TBRs showed full-thickness rupture with frank anterior intraluminal protrusion of the esophagus. In three patients, transient noninvasive positive pressure ventilatory support (NIV) was necessary. All lesions healed without sequelae. Two patients receiving mechanical ventilation underwent surgical repair and died. Thirteen patients receiving mechanical ventilation were considered at high surgical risk, and TBR bridging was attempted as salvage therapy. Complete bridging was achieved in five patients by simply advancing the endotracheal tube distal to the injury. Separate bilateral mainstem endobronchial intubation was necessary in six patients whose TBRs were too close to the carina. Nine of 13 patients (69%) treated with nonoperative therapy completely recovered. CONCLUSION: We conclude that conservative nonoperative therapy should be considered in patients with postintubation TBR who are breathing spontaneously, or when extubation is scheduled within 24 h from the time of diagnosis, or when continued ventilation is required to treat an underlying respiratory status. Surgical repair should be reserved for cases in which NIV or bridging the lesion is technically not feasible.

Adult↗

Tracheal replacement by allogenic aorta in the pig.

BACKGROUND: To assess whether fresh aortic allografts (AAs) can be used for tracheal replacement. METHODS: Twenty-one male minipigs underwent tracheal replacement using AAs harvested from female pigs. The length of replaced segments exceeded 50% of the trachea. A stent was implanted into the lumen of the AA to prevent collapse. The animals were killed at 3-month intervals, and AAs were assessed for ingrowth of respiratory epithelium and cartilage formation and tested for type II collagen formation and the presence of the SRY gene. RESULTS: A high stent migration rate was observed. Only 10 pigs and 4 pigs made it to follow-up periods exceeding 3 months and 9 months, respectively. Neither rejection nor ischemia were observed. At 3 months, a metaplastic epithelium lined the graft. At 10 months, a posterior membrane could be seen with immature cartilage and disorganized elastic fibers. SRY gene assay showed that the cells engrafted in the AAs, particularly at the level of the newly formed cartilage, were of male origin and thus originated from the recipient. CONCLUSION: This study confirms that a fresh AA, replacing more than half of the trachea of the pig, transforms into a conduit containing the major tracheal components. These components are relatively immature and do not as of yet replicate the form and function of the native trachea. Questions remain concerning the exact mechanisms of this process. Further research on the role of tracheal replacement is recommended.

Animals↗

Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: comparative effects of helium and nitrogen.

BACKGROUND: Lung deposition of intravenous cephalosporins is low. The lung deposition of equivalent doses of ceftazidime administered either intravenously or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as the carrying gas of the aerosol was compared in ventilated piglets with and without experimental bronchopneumonia. METHODS: Five piglets with noninfected lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg ceftazidime by ultrasonic nebulization. In each group, the ventilator was operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen mixture. Animals were killed, and multiple lung specimens were sampled for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography. RESULTS: As compared with intravenous administration, nebulization of ceftazidime significantly increased lung tissue concentrations (17 +/- 13 vs. 383 +/- 84 microg/g in noninfected piglets and 10 +/- 3 vs. 129 +/- 108 microg/g in piglets with experimental bronchopneumonia; P < 0.001). The use of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung tissue concentrations in noninfected piglets (576 +/- 141 microg/g; P < 0.001) and no significant change in infected piglets (111 +/- 104 microg/g). CONCLUSION: Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentrations as compared with intravenous administration. Using a helium-oxygen mixture as the carrying gas of the aerosol induced a substantial additional increase in lung deposition in noninfected piglets but not in piglets with experimental bronchopneumonia.

Administration, Inhalation↗

Diagnosis of hospital-acquired pneumonia: postmortem studies.

Postmortem human and animal studies provided important insights into the relationship between histology and bacteriology in VAP. According to the results of these studies, VAP is a multifocal and polymicrobial infectious process. The lesions are predominately located in dependent segments of lower lobes. There is no straightforward relationship between the intensity of lung damage and the local microbial burden. Histobacteriologic discrepancy may explain why even such techniques as PSB and BAL can be unreliable for the diagnosis of VAP. The histopathologic examination of the lung tissue has been traditionally regarded as the gold standard for diagnosis of VAP. Even with histology, however, pneumonia is frequently difficult to define. For daily practice, antimicrobial decisions and the guidance of antimicrobial regimens should not rely exclusively on the results of quantitative cultures in the individual patient. Instead, finding a balance between clinical judgment and microbiologic results is crucial to manage patients with VAP appropriately.

Animals↗

Endobronchial phototoxicity of WST 09 (Tookad), a new fast-acting photosensitizer for photodynamic therapy: preclinical study in the pig.

Photodynamic therapy (PDT) has been used for many years for both palliative and curative treatment of bronchial carcinomas. However, prolonged skin phototoxicity and reduced depth of penetration has limited the widespread use of PDT. We studied the endobronchial phototoxicity of a novel photosensitizer, WST 09 (Tookad). Fourteen pairs of Large White-Landrace male piglets were given intravenous WST 09 followed by laser light illumination of the left mainstem bronchus. Different settings for light dose (fluence), fluence rate (FR), drug dose (D) and drug-light interval (DLI) were applied to each pair. Bronchial toxicity was assessed with repeat bronchoscopic photographic evaluation as well as by pathologic examination following autopsy. Animals developed no toxicity, moderate toxicity or severe toxicity. Increased toxicity was seen with increasing D and fluence and decreasing DLI, whereas no increased toxicity was seen with higher FR. PDT-related histological changes in the normal bronchus confirm the vascular effect of WST 09. Depending on the parameter settings for fluence, D and DLI, the lesions ranged from focal intramucosal ischemia to transmural infarction with subsequent acute inflammation and fibrosis. Clinically feasible parameters for drug and light dosimetry were documented. These data will be important in determining safe starting doses for human phase I/II studies.

Animals↗

Experimental ventilator-associated pneumonia: distribution of lung infection and consequences for lung aeration.

Ventilator-associated pneumonia (VAP) has been described in humans and in experimental animals. The most severe lesions are located in dependent lung segments along a sterno-vertebral axis, however the cephalocaudal distribution of lung infection remains unknown. We used an experimental model to evaluate the distribution of lung infection, considering its anteroposterior and cephalocaudal gradient, and its impact on lung aeration. Ten healthy domestic piglets were anesthetized, paralyzed and mechanically ventilated for 59 hours in the prone position. At the end of the experiment they were sacrificed and their lungs were fixed. Six segments were analyzed: a non-dependant (ND) and a dependant (D) segment of the upper (UL), middle (ML) and lower (LL) lobes. The presence of healthy lung or of histological infectious lesions was analyzed with a semi-quantitative method. The regional distribution of lung infection was compared between upper, middle and lower lobes, as well as between dependant and non-dependant regions. The presence of infectious lesions was correlated with measurements of lung aeration. Nine of the ten piglets developed VAP. Infectious lesions were distributed along a sterno-vertebral and a cephalocaudal gradient; the lower and middle lobes were more frequently infected than the upper lobes. There was an inverse correlation (R= - 0.902) between the development of lung lesions and lung aeration. In conclusion, VAP was a frequent complication in healthy mechanically ventilated piglets, showing an anteroposterior as well as a cephalocaudal gradient. As expected, development of lung infection was accompanied by a corresponding loss of aeration.

Animals↗

Lung deposition and efficiency of nebulized amikacin during Escherichia coli pneumonia in ventilated piglets.

Lung tissue deposition and antibacterial efficiency of nebulized and intravenous amikacin (AMK) were compared in anesthetized and ventilated piglets suffering from a bronchopneumonia produced by the intrabronchial inoculation of Escherichia coli. AMK was administered 24 hours after the inoculation either through an ultrasonic nebulizer (45 mg x kg-1, n = 10) or by intravenous infusion (15 mg x kg-1, n = 8). Piglets were killed 1 hour after a second AMK administration performed 24 hours after the first one, and lung tissue concentrations of AMK and lung bacterial burden were assessed on multiple lung specimens. The amount of nebulized AMK reaching the tracheobronchial tree represented 38 +/- 6% of the initial nebulizer AMK charge. After nebulization, AMK lung tissue concentrations were 3- to 30-fold higher than after intravenous administration and were influenced by the severity of lung lesions: 188 +/- 175 microg x g-1 in lung segments with mild bronchopneumonia versus 40 +/- 65 microg x g-1 in lung segments with severe bronchopneumonia (p < 0.01). Lung bacterial burden was significantly lower in the aerosol group than in the intravenous group (median = 0 colony forming units. g-1 versus median = 5 x 10(2) colony forming units x g-1, p < 0.001). In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration.

Administration, Inhalation↗

Lung tissue concentrations of nebulized amikacin during mechanical ventilation in piglets with healthy lungs.

The tissue concentration of aminoglycosides in lung parenchyma is the main determinant of bactericidal efficiency. The aim of the study was to compare the lung deposition of amikacin administered either by an ultrasonic nebulizer or by intravenous infusion during mechanical ventilation. Eighteen healthy ventilated piglets received a single daily dose of amikacin by intravenous infusion (15 mg. kg(-1)) and 18 by aerosol (1 g in 12 ml). The amount of aerosolized amikacin reaching the tracheobronchial tree represented 40 +/- 5% of the initial dose with an aerodynamic size distribution showing 50% of particles ranging between 0.5 and 5 microm mass median diameter. Animals were killed at different time intervals after the second dose. Tissue concentrations of amikacin were determined on cryomixed multiple lung specimen by an immunoenzymatic method. The lung concentrations of nebulized amikacin, peaking at 208 +/- 76 microg. g(-1), were more than 10-fold higher than the lung concentrations of intravenous amikacin and were homogeneously distributed throughout the lung parenchyma. Amikacin plasma concentrations lower than 5 mmol. l(-1) were measured after the sixth hour after the nebulization. In conclusion, the ultrasonic nebulization of amikacin resulted in high tissue concentrations, far above the minimal inhibitory concentrations of most gram-negative strains.

Administration, Inhalation↗

Influence of lung aeration on pulmonary concentrations of nebulized and intravenous amikacin in ventilated piglets with severe bronchopneumonia.

BACKGROUND: Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma. Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration. METHODS: An experimental bronchopneumonia was induced in anesthetized piglets by inoculating lower lobes with a suspension of 10(6) cfu/ml Escherichia coli. After 24 h of mechanical ventilation, 7 animals received two intravenous injections of 15 mg/kg amikacin, and 11 animals received two nebulizations of 40 mg/kg amikacin at 24-h intervals. One hour following the second administration, animals were killed, and multiple lung specimens were sampled for assessing amikacin pulmonary concentrations and quantifying lung aeration on histologic sections. RESULTS: Thirty-eight percent of the nebulized amikacin (15 mg/kg) reached the tracheobronchial tree. Amikacin pulmonary concentrations were always higher after nebulization than after intravenous administration, decreased with the extension of parenchymal infection, and were significantly influenced by lung aeration: 197 +/- 165 versus 6 +/- 5 microg/g in lung segments with focal bronchopneumonia (P = 0.03), 40 +/- 62 versus 5 +/- 3 microg/g in lung segments with confluent bronchopneumonia (P = 0.001), 18 +/- 7 versus 7 +/- 4 microg/g in lung segments with lung aeration of 30% or less, and 65 +/- 9 versus 2 +/- 3 microg/g in lung segments with lung aeration of 50% or more. CONCLUSIONS: In a porcine model of severe bronchopneumonia, the nebulization of amikacin provided 3-30 times higher pulmonary concentrations than the intravenous administration of an equivalent dose. The greater the lung aeration, the higher were the amikacin pulmonary concentrations found in the infected lung segments.

Amikacin↗

Endobronchial electrocautery and argon plasma coagulation: a practical approach.

The present review covers the technical and practical aspects of endobronchial electrocautery, including argon plasma coagulation, which have great potential for widespread use by pulmonologists around the world. The various electrocautery modes, power settings and electrode probes are described in detail, and the authors' clinical and technical approach is demonstrated with a narrative description and brief case presentations. Malignant airway obstruction, hemoptysis, web-like stenosis, stent related granulation tissue and early lung carcinomas are the most common indications for treatment. Advantages of electrocautery, such as low cost, rapid effect, safety and ease of use, are contrasted to other endobronchial therapeutic modalities. Published experience with electrocautery is reviewed.

Bronchial Diseases↗