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1.
Pulm Pharmacol Ther ; 57: 101807, 2019 08.
Article in English | MEDLINE | ID: mdl-31102741

ABSTRACT

BACKGROUND: Nebulization during mechanical ventilation is impeded by large extra-pulmonary drug deposition and long administration durations which currently limit implementation of inhaled antibiotic therapy. Direct intra-tracheal delivery using a sprayer represents an appealing alternative investigated in small animal models, but large animal data are lacking. METHODS: Amikacin was administered through intravenous infusion (20 mg/kg), nebulization (60 mg/kg) and direct intra-tracheal spray (30 mg/kg) to 10 intubated piglets, in a randomized cross-over design. Amikacin concentrations were measured in the serum and pulmonary parenchyma. Anatomic deposition was investigated using immuno-histochemistry. RESULTS: Spray delivery resulted in higher amikacin outputs than nebulization and infusion. Pulmonary inhaled delivery techniques yielded much higher lung concentrations and much lower serum concentrations than intravenous infusion. However, unlike nebulization and infusion, intra-tracheal spray delivery was associated with more than 100- and 1000-fold variability in lung concentrations between and within animals. Amikacin specific immuno-histochemistry showed consistent bronchial and alveolar drug deposition with all modalities. CONCLUSION: Nebulization remains the most reliable and simple technique to deliver inhaled amikacin uniformly to the lung during mechanical ventilation. Further development of tracheal sprays is required to take advantage of potential benefits related to high drug output and low extra-pulmonary deposition in large animals.


Subject(s)
Amikacin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Drug Delivery Systems/methods , Lung/metabolism , Aerosols , Animals , Infusions, Intravenous , Inhalation , Intubation , Models, Anatomic , Models, Animal , Nebulizers and Vaporizers , Swine , Trachea
2.
Int J Med Microbiol ; 304(3-4): 327-38, 2014 May.
Article in English | MEDLINE | ID: mdl-24360996

ABSTRACT

Invasive pulmonary aspergillosis remains a matter of great concern in oncology/haematology, intensive care units and organ transplantation departments. Despite the availability of various diagnostic tools with attractive features, new markers of infection are required for better medical care. We therefore looked for potential pulmonary biomarkers of aspergillosis, by carrying out two-dimensional (2D) gel electrophoresis comparing the proteomes of bronchial-alveolar lavage fluids (BALF) from infected rats and from control rats presenting non-specific inflammation, both immunocompromised. A bioinformatic analysis of the 2D-maps revealed significant differences in the abundance of 20 protein spots (ANOVA P-value<0.01; q-value<0.03; power>0.8). One of these proteins, identified by mass spectrometry, was considered of potential interest: inter-alpha-inhibitor H4 heavy-chain (ITIH4), characterised for the first time in this infectious context. Western blotting confirmed its overabundance in all infected BALF, particularly at early stages of murine aspergillosis. Further investigations were carried on rat serum, and confirmed that ITIH4 levels increased during experimental aspergillosis. Preliminary results in human samples strengthened this trend. To our knowledge, this is the first description of the involvement of ITIH4 in aspergillosis.


Subject(s)
Alpha-Globulins/analysis , Aspergillosis/diagnosis , Biomarkers/analysis , Bronchoalveolar Lavage Fluid/chemistry , Animals , Biomarkers/blood , Blotting, Western , Disease Models, Animal , Electrophoresis, Gel, Two-Dimensional , Male , Rats, Sprague-Dawley , Serum/chemistry
4.
Ann Pathol ; 32(3): 224-8, 2012 Jun.
Article in French | MEDLINE | ID: mdl-22748343

ABSTRACT

We present the case of an embryonal rhabdomyosarcoma of orbitary location with aberrant expression of epithelial markers in a 51-year-old female. The rhabdomyosarcoma is a rare tumor of soft tissues affecting mainly the child, but also exceptionally adults over 50. When it presents as a small round cells tumor, particularly in the region of head and neck, its differential diagnosis with several other poorly differentiated tumors may be difficult. Several cases of rhabdomyosarcoma with aberrant expression of epithelial markers have been reported in the literature. A large immunohistochemical panel is recommended by recent studies in order to avoid diagnostic errors. It includes large spectrum cytokeratins, desmin, neuroendocrine, melanocytic and lymphoid markers. Our observation confirms the importance of conducting this immunohistochemical panel including desmin in the context of a poorly differentiated tumor of the head and neck region. It should be performed whatever the age of the patient and even if the tumor expresses epithelial markers.


Subject(s)
Orbital Neoplasms/chemistry , Orbital Neoplasms/pathology , Rhabdomyosarcoma, Embryonal/chemistry , Rhabdomyosarcoma, Embryonal/pathology , Biomarkers, Tumor/analysis , Biomarkers, Tumor/biosynthesis , Diagnostic Errors , Female , Humans , Middle Aged , Orbital Neoplasms/metabolism , Rhabdomyosarcoma, Embryonal/metabolism
5.
Ann Pathol ; 29(3): 233-7, 2009 Jun.
Article in French | MEDLINE | ID: mdl-19619832

ABSTRACT

The association of a pseudomyxoma peritonei with a mucinous tumor of the appendix and/or the ovary is regularly reported in the literature. However, in this context, endometrial or endocervical lesions remain exceptional. We report the case of a 57-year-old patient, with pseudomyxoma peritonei associated with a low-grade mucinous neoplasia of appendix and both ovaries. The systematic sampling of endometrium and endocervix showed small segments of intestinal epithelium admixed with native epithelium. Histological and immunohistochemical characteristics of this epithelium were quite comparable to those observed in the appendix and ovaries. The endocervical and endometrial lesions might represent an implantation of mucinous epithelium from appendix, emphasizing the capacity of this epithelium to implant at a distance from the original lesion.


Subject(s)
Adenocarcinoma, Mucinous/complications , Appendiceal Neoplasms/complications , Cervix Uteri/pathology , Endometrium/pathology , Neoplasms, Multiple Primary/pathology , Ovarian Neoplasms/complications , Pseudomyxoma Peritonei/etiology , Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma, Mucinous/pathology , Adenocarcinoma, Mucinous/surgery , Appendectomy , Appendiceal Neoplasms/diagnosis , Appendiceal Neoplasms/pathology , Appendiceal Neoplasms/surgery , Breast Neoplasms/diagnosis , Carcinoma, Ductal, Breast/diagnosis , Epithelial Cells/pathology , Female , Humans , Hysterectomy , Metaplasia , Middle Aged , Neoplasm Invasiveness , Neoplasms, Multiple Primary/complications , Neoplasms, Multiple Primary/diagnosis , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Ovariectomy , Pseudomyxoma Peritonei/pathology
6.
Ann Pathol ; 27(5): 345-51, 2007 Oct.
Article in French | MEDLINE | ID: mdl-18185469

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate our practices concerning difficult lesions sent for second opinion to an expert. MATERIAL AND METHODS: We analyzed retrospectively all the requests for second opinion carried out over one year in our laboratory. The following data were indexed: organ, pathology (tumoral or not), type of sampling, the time, additional techniques carried out by the expert and comparison of the initial diagnosis with that of the expert. A provisional report was systematically performed before sending the observation to the expert. RESULTS: Among the 54 cases, 40 lesions were tumoral and 31 malignant. The type of pathology which were more often sent for opinion were lymphomas (18.5%) and soft tissue tumors (11%). The average time between reception of the sampling in our laboratory and the answer of the expert was 32.8 days. In 40.7% of the cases, additional techniques like immunohistochemistry (19 cases) or molecular biology (7 cases) were carried out by the expert and concerned especially lymphomas or soft tissue pathology. The comparison of the initial diagnosis with that of the expert showed no change in 53.7% of cases, 13% of divergence from benign-malignant (6 cases) or malignant-benign (1 case) type, 16.7% of changes of classification without modification of the benignity or the malignity, and 16.7% of difficult interpretation. CONCLUSION: This study seems to be a good means of evaluating our professional practices related to difficult lesions and confirms the importance of deep-freezing tumors, holding multidisciplinary meetings and participating in specialized working groups.


Subject(s)
Hospitals, General/statistics & numerical data , Neoplasms/pathology , Referral and Consultation/statistics & numerical data , Biopsy , Brain Diseases/pathology , France , Humans , Retrospective Studies
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