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1.
BMJ Mil Health ; 167(4): 269-274, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32759228

ABSTRACT

'We are at war', French President Emmanuel Macron said in an address to the nation on 16 March 2020. As part of this national effort, the French Military Medical Service (FMMS) is committed to the fight against COVID-19. This original report aimed to describe and detail actions that the FMMS has carried out in the nationwide fight against the COVID-19 pandemic in France, as well as overseas. Experts in the field reported major actions conducted by the FMMS during the COVID-19 pandemic in France. In just few weeks, the FMMS developed ad hoc medical capabilities to support national health authorities. It additionally developed adaptive, collective en route care via aeromedical and naval units and deployed a military intensive care field hospital. A COVID-19 crisis cell coordinated the French Armed Forces health management. The French Military Centre for Epidemiology and Public Health provided all information needed to guide the decision-making process. Medical centres of the French Armed Forces organised the primary care for military patients, with the widespread use of telemedicine. The Paris Fire Brigade and the Marseille Navy Fire Battalion emergency departments ensured prehospital management of patients with COVID-19. The eight French military training hospitals cooperated with civilian regional health agencies. The French military medical supply chain supported all military medical treatment facilities in France as well as overseas, coping with a growing shortage of medical equipment. The French Armed Forces Biomedical Research Institute performed diagnostics, engaged in multiple research projects, updated the review of the scientific literature on COVID-19 daily and provided expert recommendations on biosafety. Finally, even students of the French military medical academy volunteered to participate in the fight against the COVID-19 pandemic. In conclusion, in an unprecedented medical crisis, the FMMS engaged multiple innovative and adaptive actions, which are still ongoing, in the fight against COVID-19. The collaboration between military and civilian healthcare systems reinforced the shared objective to achieve the goal of 'saving the greatest number'.


Subject(s)
COVID-19 , Communicable Disease Control/organization & administration , Military Medicine/organization & administration , Pandemics , France , Humans , Military Personnel , Mobile Health Units , Public Health Administration
2.
BMJ Mil Health ; 167(4): 224-228, 2021 Aug.
Article in English | MEDLINE | ID: mdl-32764134

ABSTRACT

INTRODUCTION: An amphibious assault ship was deployed on 22 March in Corsica to carry out medical evacuation of 12 critical patients infected with COVID-19. The ship has on-board hospital capacity and is the first time that an amphibious assault ship is engaged in this particular condition. The aim is to evaluate the feasibility and safety of prolonged medical evacuation of critical patients with COVID-19. METHODS: We included 12 patients with confirmed COVID-19 infection: six ventilated patients with acute respiratory distress syndrome and six non-ventilated patients with hypoxaemia. Transfer on an amphibious assault ship lasted 20 hours. We collected patients' medical records: age, comorbidities, COVID-19 history and diagnosis, ventilation supply and ventilator settings, and blood gas results. We calculated oxygen consumption (OC). RESULTS: All patients had a medical history. The median delay from onset of symptoms to hospitalisation was 8 (7-10) days. The median Sequential Organ Failure Assessment score on admission was 3 (2-5). There was no significant increase in oxygen during ship transport and no major respiratory complication. There was no significant increase in arterial oxygen pressure to fractional inspired oxygen ratio among ventilated patients during ship transport. Among ventilated patients, the median calculated OC was 255 L (222-281) by hours and 5270 L (4908-5616) during all ship transport. Among non-ventilated patients, the median calculated OC was 120 L (120-480) by hours and 2400 L (2400-9600) during all ship transport. CONCLUSION: The present work contributes to assessing the feasibility and safety condition of critical COVID-19 evacuation on an amphibious assault ship during an extended transport. The ship needs to prepare a plan and a specialised intensive team and conduct patient screening for prolonged interhospital transfers.


Subject(s)
COVID-19/complications , Military Medicine , Military Personnel , Patient Transfer , Ships , Aged , COVID-19/therapy , Feasibility Studies , Female , France , Hospitalization , Humans , Male , Middle Aged , Oxygen Consumption , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology , Retrospective Studies , Time-to-Treatment
3.
Arch Pediatr ; 26(3): 133-137, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30885602

ABSTRACT

Lyme neuroborreliosis is a bacterial infection caused by the dissemination and proliferation of a Borrelia species in the central nervous system. Neuroborreliosis occurs after transmission of the pathogen from an infected tick to a human host during a tick bite. We report nine cases of pediatric neuroborreliosis collected by the National Observatory of Pediatric Bacterial Meningitis in France between 2001 and 2012. The nine children, aged 4-13 years, were identified in northern and eastern France and had the following clinical features: meningeal irritation alone or with facial palsy, or isolated facial palsy. All cases showed anti-Borrelia antibodies in cerebrospinal fluid or serum, or with a positive Borrelia PCR in the CSF. The outcome was favorable in all cases after a 2- to 3-week course of third-generation cephalosporin. On the basis of these nine pediatric cases, this study provides an update on the epidemiology, pathophysiology, diagnostic strategy, and treatment of neuroborreliosis, with insight into the specific features of pediatric neuroborreliosis and the difficulties encountered in the diagnosis of this infection.


Subject(s)
Lyme Neuroborreliosis/diagnosis , Adolescent , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antibodies, Bacterial/blood , Antibodies, Bacterial/cerebrospinal fluid , Borrelia/genetics , Borrelia/immunology , Cefotaxime/therapeutic use , Ceftriaxone/therapeutic use , Child , Child, Preschool , DNA, Bacterial , Facial Paralysis/microbiology , Female , France , Humans , Lyme Neuroborreliosis/drug therapy , Male , Polymerase Chain Reaction
4.
Chem Soc Rev ; 47(14): 5312-5337, 2018 Jul 17.
Article in English | MEDLINE | ID: mdl-29770369

ABSTRACT

The applications of nanoparticles (NPs) are increasing exponentially in consumer products, biotechnology and biomedicine, and humans, as well as the environment, are increasingly being exposed to NPs. Analogously, various (pathogenic) microorganisms are present at all the major exposure and entry sites for NPs in the human body as well as in environmental habitats. However, the field has just started to explore the complex interplay between NPs and microbes and the (patho)biological consequences. Based on recent insights, herein, we critically reviewed the available knowledge about the interaction of NPs with microbes and the analytical investigations including the latest intravital imaging tools. We have commented on how the NPs' characteristics influence complex formation with microorganisms, presented the underlying physicochemical forces, and provided examples of how this knowledge can be used to rationally control the NP-microbe interaction. We concluded by discussing the role of the biomolecule corona in NP-microbe crosstalk and speculated the impact of NP-microbe complex formation on the (patho)biological outcome and fate of microbial pathogens. The presented insights will not only support the field in engineering NPs with improved anti-microbial activity but also stimulate research on the biomedical and toxicological relevance of nanomaterial-microbiome complex formation for the anthropocene in general.


Subject(s)
Gram-Negative Bacteria/metabolism , Gram-Positive Bacteria/metabolism , Nanoparticles/metabolism , Spores, Fungal/metabolism , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Humans , Microalgae/drug effects , Microalgae/metabolism , Nanoparticles/chemistry , Nanoparticles/toxicity , Optical Imaging , Pollen/drug effects , Pollen/metabolism , Spores, Fungal/drug effects
6.
J Hosp Infect ; 83(4): 341-3, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23337251

ABSTRACT

An unusual multi-drug-resistant Pseudomonas aeruginosa (MDR-PA) was isolated in four patients whilst hospitalized in a French teaching hospital between May and August 2011. All four patients had undergone an oesophago-gastro-duodenoscopy with the same gastroscope over a five-month period. This endoscope was associated with a culture positive for the MDR-PA. Observations of endoscope reprocessing identified deviations from the agreed processes: insufficient initial cleaning, shortening of the immersion time and brushing time, insufficient channel flushing, and inadequate drying prior to storage. Since withdrawing the gastroscope and institution of strict adherence to the agreed processes, no other MDR-PA cases have been isolated.


Subject(s)
Cross Infection/transmission , Gastroscopy/adverse effects , Pseudomonas Infections/transmission , Pseudomonas aeruginosa/enzymology , beta-Lactamases/metabolism , Adult , Aged , Aged, 80 and over , Cross Infection/microbiology , Disinfection/methods , Drug Resistance, Multiple, Bacterial , France , Gastroscopes/microbiology , Guideline Adherence , Hospitals, Teaching , Humans , Infection Control/methods , Middle Aged , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification
7.
Arch Pediatr ; 18(5): 518-21, 2011 May.
Article in French | MEDLINE | ID: mdl-21458975

ABSTRACT

Among 76 children fully vaccinated with 7-valent conjugate vaccine and subsequently hospitalized from 2006 to 2009 for community-acquired pneumonia, isolated or with empyema or pleuritis, 10 had confirmed pneumococcal infections. All pneumococci isolated with blood or pleural culture were non vaccine serotypes (1, 5, 7F, and 19A). The proportion of pneumococcal pneumonias was similar to that in two series from the same hospital before the vaccine era. These data show that the 13-valent conjugate vaccine could be useful in prevention of community-acquired pneumonia and that bacteriologic survey of community-acquired pneumonia remains necessary.


Subject(s)
Heptavalent Pneumococcal Conjugate Vaccine , Pneumonia, Pneumococcal/microbiology , Pneumonia, Pneumococcal/prevention & control , Streptococcus pneumoniae/isolation & purification , Adolescent , Child , Child, Preschool , Community-Acquired Infections/microbiology , Hospitalization , Humans , Infant , Prospective Studies
8.
Arch Pediatr ; 17(11): 1522-6, 2010 Nov.
Article in French | MEDLINE | ID: mdl-20833005

ABSTRACT

During the months of October and November 2006-2008, norovirus was detected in the stools of 14 children hospitalized with acute diarrhea (no sapovirus). Nine of these noroviruses belonged to a unique GGII4 strain, which produced severe clinical symptoms, present only in 2007 and 2008 and absent in 2006. This strain, identified in Europe mainly in the elderly, seems to be on the rise in children in the Paris area over the past few years.


Subject(s)
Caliciviridae Infections/epidemiology , Caliciviridae Infections/virology , Feces/virology , Gastroenteritis/epidemiology , Gastroenteritis/virology , Inpatients/statistics & numerical data , Norovirus/isolation & purification , Adolescent , Caliciviridae Infections/diagnosis , Caliciviridae Infections/genetics , Child , Child, Preschool , Gastroenteritis/diagnosis , Genetic Variation , Genotype , Humans , Infant , Norovirus/genetics , Paris/epidemiology , Retrospective Studies
9.
Gastroenterol Clin Biol ; 34(10): 549-53, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20822873

ABSTRACT

OBJECTIVE: Closure of the fistula tract with an anal fistula plug has been reported to provide success rates as high as 80%. The purpose of this study was to evaluate our results with this new method. METHOD: From June 2006 to September 2007, an anal fistula plug was used for the treatment of high transsphincteric fistulas. Success was defined as no residual leakage or abscess formation and closure of the external opening. RESULTS: Fifteen patients (seven women), median age 46 years (range 32-58 years), were included in the study. Three had Crohn's disease, three had an anovulvar fistula and seven had undergone previous surgical-repair attempts. Three patients expelled the prosthesis on postoperative day 2, 5 and 7, respectively, and a second plug placement was followed by expulsion again. One patient developed an abscess that was noted on postoperative day 4. The fistula tract healed in 6/15 patients (40%) after 3 months and in 8/15 (53.3%) after 7 months. The success rate in Crohn's disease was 33%. No significant difference was found between patients with or without previous surgical repair. CONCLUSION: In our experience, this simple technique provided success rates of 40% at 3 months and 53% at 7 months.


Subject(s)
Rectal Fistula/surgery , Tampons, Surgical , Adult , Bioprosthesis , Crohn Disease/complications , Digestive System Surgical Procedures/methods , Female , Humans , Male , Middle Aged , Rectal Fistula/etiology , Rectovaginal Fistula/surgery , Recurrence , Retrospective Studies , Risk Factors , Suture Techniques/instrumentation , Time Factors , Treatment Outcome , Wound Healing
11.
Arch Pediatr ; 17(4): 373-7, 2010 Apr.
Article in French | MEDLINE | ID: mdl-20189361

ABSTRACT

Invasive pneumococcal diseases were reduced after introduction of pneumococcal conjugate vaccine, but infections due to non-vaccine serotypes persisted. The pneumococcal origin of community-acquired pneumonia remains difficult to affirm, but high procalcitonin and C-reactive protein blood levels and duration of fever 48 h or less after initial antibiotic treatment are excellent predictors of pneumococci. Among 259 patients under 7 years of age hospitalized from 2003 to 2008 for community-acquired pneumonia, 47 met these criteria, including 27 of 141 hospitalized between 2006 (date of vaccine generalization) and 2008. Of these 27, 21 had previously received pneumococcal conjugate vaccine and 19 of 21 were attendees of nursery school or day care centers versus only 2 in 2003-2006. These data show that pneumococcal pneumonias are possible in immunized children cared for in-group settings.


Subject(s)
Child Day Care Centers , Community-Acquired Infections/prevention & control , Pneumococcal Vaccines/administration & dosage , Pneumonia, Pneumococcal/prevention & control , Pneumonia, Pneumococcal/transmission , Schools, Nursery , C-Reactive Protein/metabolism , Calcitonin/blood , Calcitonin Gene-Related Peptide , Child , Child, Preschool , Community-Acquired Infections/diagnosis , Community-Acquired Infections/microbiology , Community-Acquired Infections/transmission , Female , France , Hospitalization/statistics & numerical data , Humans , Infant , Male , Pneumonia, Pneumococcal/diagnosis , Pneumonia, Pneumococcal/microbiology , Protein Precursors/blood , Risk Factors , Serotyping
12.
Colorectal Dis ; 12(3): 247-53, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19508523

ABSTRACT

OBJECTIVE: Before undergoing sacral nerve stimulation (SNS) for faecal incontinence (FI), patients are investigated with morphologic, dynamic and electrophysiologic tests. The purpose of our study was to evaluate their value in the selection of patients who may benefit most from neuromodulation. METHOD: If temporary stimulation resulted in a good objective response, a permanent neuromodulator was implanted. Patients were reviewed at 3 months and then at 6 monthly intervals. Asked by telephone, patient's satisfaction was described as good, satisfactory or poor. RESULTS: Forty-five consecutive patients (41 females, median age 59 years) with FI (Wexner 16.1 +/- 2.9) underwent SNS. Temporary stimulation was successful in 32 (71)% patients. At a median follow-up of 33 months, the neuromodulator remained in place in 25 (55%) patients, two do whom switched it off, leaving 23 (51%) with a functioning neuromodulator. There was no statistically significant difference between the characteristics (including manometry, ultrasound and electrophysiology) of patients undergoing implantation (n = 32) or not (n = 13) and those with or without a functioning stimulator (n = 23: n = 13). In the 23 patients with a functioning stimulator the result was good in 12, satisfactory in five and poor in six. There was no statistically significant difference in the patient characteristics between those with a good result (n = 12) and the remainder (n = 32). CONCLUSION: The findings suggest that investigation for FI does not facilitate patient selection for SNS and cannot be used to predict outcome.


Subject(s)
Anal Canal/innervation , Electric Stimulation Therapy/methods , Fecal Incontinence/therapy , Patient Selection , Rectum/innervation , Aged , Electrodes, Implanted , Female , Follow-Up Studies , Humans , Lumbosacral Plexus , Male , Middle Aged , Patient Satisfaction , Treatment Failure
13.
Med Mal Infect ; 39(6): 353-5, 2009 Jun.
Article in French | MEDLINE | ID: mdl-19062209

ABSTRACT

Human Bocavirus (HboV) was recently cloned by a systematic screening of nasopharyngeal samples from children hospitalized for respiratory tract infections. This virus, genus Bocavirus, family Parvoviridae, was identified by screening for its DNA in 5% of nasopharyngeal aspirates, as reported in several studies. It may be responsible for upper and lower respiratory tract infections of young children under five years with a peak rate in winter. Because of a high rate of viral co-infections, its pathogenic role in these infections should be documented. Further studies are required to determine the role of this possibly systemic virus in other affections.


Subject(s)
Bocavirus , Nasopharyngeal Diseases/virology , Parvoviridae Infections/epidemiology , Bocavirus/genetics , Bocavirus/isolation & purification , Child, Preschool , France/epidemiology , Humans , Infant , Nasopharyngeal Diseases/epidemiology , Nasopharynx/virology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology
15.
Mar Pollut Bull ; 53(1-4): 80-90, 2006.
Article in English | MEDLINE | ID: mdl-16249007

ABSTRACT

Using a Before/During/After sampling protocol, the effects of the Le Havre harbour extension, which was started at the end of 2001, on the macrobenthic and suprabenthic communities in the eastern Bay of Seine (English Channel) were examined. As the construction phase has not yet been completed, the results presented here reflect only the data collected before and during the operations (September 2000 and 2002 for benthos sampling and March 2001, September 2001, October 2002 and March 2003 for suprabenthos sampling). Although bio-sedimentary changes did occur at the mouth of the Seine river, an analysis of benthic assemblages reveals that the dredging and construction operations do not seem to have influenced assemblage structure or the spatial distribution of organisms. Comparisons of the suprabenthic assemblages at each sampling date indicate that seasonal dynamics was mainly responsible for determining species distribution. We conclude that, 1 year into the harbour management plan, the observed changes in benthic and suprabenthic assemblage abundance do not exceed the range of spatial variability that exists naturally in the Seine estuary. Despite this compensatory actions designed to protect the aquatic habitats and to preserve a sustainable and healthy ecosystem have been added to the infrastructure development plan.


Subject(s)
Ecosystem , Environmental Monitoring/statistics & numerical data , Geologic Sediments/analysis , Invertebrates/growth & development , Adaptation, Physiological , Animals , Data Collection , Facility Design and Construction , France , Invertebrates/physiology , Population Dynamics
16.
Arch Pediatr ; 13(1): 57-63, 2006 Jan.
Article in French | MEDLINE | ID: mdl-16274977

ABSTRACT

Cystic fibrosis is the most common lethal autosomal recessive disease among the Caucasian population. It is caused by defects in the CFTR gene (Cystic Fibrosis Transmembrane Conductance Regulator). Although over 1600 disease-causing mutations in the CFTR gene have been described, the highly variable disease phenotype in cystic fibrosis cannot be explained on the basis of this gene alone. Both the environment and other non-CFTR genes are likely to be important. The increased understanding of pathophysiological processes in the cystic fibrosis lung has led to several studies on genes in these pathways. One of the major aims of such studies is to produce targets for novel drug developments.


Subject(s)
Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Cystic Fibrosis/genetics , Cystic Fibrosis/physiopathology , Child , Cystic Fibrosis/drug therapy , Genetic Predisposition to Disease , Humans , Mutation , Phenotype , Polymorphism, Genetic
17.
Eur J Vasc Endovasc Surg ; 28(4): 397-9, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15350562

ABSTRACT

Recurrent puncture of dialysis grafts can cause erosion and ulcer formation in the skin over the prosthetic material. Contamination of the wound can lead to infection of the graft, and the necessity to remove it. We describe four cases where agressive treatment with debridement, intravenous antibiotics and negative pressure therapy allowed prosthesis salvage without discontinuation of hemodialysis.


Subject(s)
Blood Vessel Prosthesis/adverse effects , Renal Dialysis/adverse effects , Salvage Therapy , Surgical Wound Dehiscence/etiology , Vacuum Curettage , Aged , Anti-Bacterial Agents/therapeutic use , Catheterization, Central Venous/adverse effects , Coated Materials, Biocompatible/adverse effects , Combined Modality Therapy , Debridement , Female , Hematoma/etiology , Hematoma/therapy , Humans , Male , Polytetrafluoroethylene/adverse effects , Prosthesis-Related Infections/etiology , Prosthesis-Related Infections/therapy , Staphylococcal Infections/etiology , Staphylococcal Infections/therapy , Surgical Wound Dehiscence/therapy
18.
Rev Mal Respir ; 21(3 Pt 1): 567-71, 2004 Jun.
Article in French | MEDLINE | ID: mdl-15292849

ABSTRACT

INTRODUCTION: Lung Volume reduction surgery (LVRS) is a recognized therapeutic option for patients presenting with severe and disabling pulmonary emphysema. Case selection is based upon clinical, morphological and functional criteria. STATE OF THE ART: LVRS has shown promising results, with improvements in exercise capacity, pulmonary function and quality of life, in selected patients with severe and disabling emphysema. A variety of surgical techniques have been described. The procedure may be unilateral or bilateral, through a sternotomy or by a video-assisted thoracoscopic (VATS) technique. The controversial aspects of the surgical technique will be analysed and discussed in the following review. PERSPECTIVES: A bilateral approach clearly offers a better functional improvement when compared to a unilateral procedure, however, the postoperative functional decline appears greater and more rapid after a bilateral procedure. A unilateral approach, with often less postoperative morbidity, allows the option to perform a future contra-lateral procedure in the event of further clinical or functional deterioration. CONCLUSIONS: In selected cases LVRS is an effective treatment for severe pulmonary emphysema. Different surgical techniques have been described. Nowadays VATS is considered to be the technique of choice, with the option to carry out a future unilateral or bilateral procedure.


Subject(s)
Pneumonectomy/methods , Pulmonary Emphysema/surgery , Humans
19.
Arch Pediatr ; 10(12): 1056-60, 2003 Dec.
Article in French | MEDLINE | ID: mdl-14643533

ABSTRACT

UNLABELLED: Children without chronic or serious medical conditions are at increased risk for hospitalization during influenza seasons, mainly with respiratory tract infections. But influenza virus infections frequently remain undiagnosed, even in hospitalized patients. We prospectively studied the rate of concomitant and preceding influenza infections in children hospitalized with a community acquired pneumonia (CAP). POPULATION AND METHODS: All 1-15-year-old children with CAP requiring hospitalization between 1st April 2000 and 2002 had nasopharyngeal aspirate for viruses, immunofluorescence and serologies for respiratory pathogens. The peak of influenza IgG measured by complement fixation (CF) is transient, and a titer of 1/64 or more indicates an acute influenza infection in the preceding weeks. Children with chronic disease were excluded and a control group of patients from outpatient clinic was measured. RESULTS: Among 33 previously healthy children (age 4.9 years, range 1.2-14 years), 8 had a pneumococcal pneumonia, 10 a pneumonia caused by Mycoplasma pneumoniae (MP), 1 by Chlamydia pneumonia, and 8 of unknown origin. In six patients immunofluorescence was positive: Respiratory Syncitial Virus, 2, Adenovirus, 1 and Influenza A, 3 (including a patient with concomitant MP infection). Thirteen of the 33 children (39.4%) had evidence of a recent influenza A infection with CF ab > or = 1/64: with pneumococcal pneumonia, 5/10 with MP pneumonia, 3/8 with unknown origin pneumonia, 9/13 of these previous influenza infections being clinically inapparent. Only 1/30 children of control group (3.3%) had CF ab > or = 1/64. CONCLUSION: In this study, influenza infection is the direct cause of CAP of children in 12% of cases. In other children with CAP, 39.4% of patients had an influenza infection in the preceding weeks which leads to secondary infection caused by Streptococcus pneumoniae or by MP or other pathogens.


Subject(s)
Influenza, Human/complications , Pneumonia/epidemiology , Pneumonia/etiology , Adolescent , Child , Child, Preschool , Community-Acquired Infections , Female , Hospitalization/statistics & numerical data , Humans , Infant , Influenza A virus/pathogenicity , Influenza B virus/pathogenicity , Male , Prospective Studies , Risk Factors
20.
J Pharm Biomed Anal ; 33(3): 475-94, 2003 Oct 15.
Article in English | MEDLINE | ID: mdl-14550866

ABSTRACT

Doxorubicin is an antineoplasic agent active against sarcoma pulmonary metastasis, but its clinical use is hampered by its myelotoxicity and its cumulative cardiotoxicity, when administered systemically. This limitation may be circumvented using the isolated lung perfusion (ILP) approach, wherein a therapeutic agent is infused locoregionally after vascular isolation of the lung. The influence of the mode of infusion (anterograde (AG): through the pulmonary artery (PA); retrograde (RG): through the pulmonary vein (PV)) on doxorubicin pharmacokinetics and lung distribution was unknown. Therefore, a simple, rapid and sensitive high-performance liquid chromatography method has been developed to quantify doxorubicin in four different biological matrices (infusion effluent, serum, tissues with low or high levels of doxorubicin). The related compound daunorubicin was used as internal standard (I.S.). Following a single-step protein precipitation of 500 microl samples with 250 microl acetone and 50 microl zinc sulfate 70% aqueous solution, the obtained supernatant was evaporated to dryness at 60 degrees C for exactly 45 min under a stream of nitrogen and the solid residue was solubilized in 200 microl of purified water. A 100 microl-volume was subjected to HPLC analysis onto a Nucleosil 100-5 microm C18 AB column equipped with a guard column (Nucleosil 100-5 microm C(6)H(5) (phenyl) end-capped) using a gradient elution of acetonitrile and 1-heptanesulfonic acid 0.2% pH 4: 15/85 at 0 min-->50/50 at 20 min-->100/0 at 22 min-->15/85 at 24 min-->15/85 at 26 min, delivered at 1 ml/min. The analytes were detected by fluorescence detection with excitation and emission wavelength set at 480 and 550 nm, respectively. The calibration curves were linear over the range of 2-1000 ng/ml for effluent and plasma matrices, and 0.1 microg/g-750 microg/g for tissues matrices. The method is precise with inter-day and intra-day relative standard deviation within 0.5 and 6.7% and accurate with inter-day and intra-day deviations between -5.4 and +7.7%. The in vitro stability in all matrices and in processed samples has been studied at -80 degrees C for 1 month, and at 4 degrees C for 48 h, respectively. During initial studies, heparin used as anticoagulant was found to profoundly influence the measurements of doxorubicin in effluents collected from animals under ILP. Moreover, the strong matrix effect observed with tissues samples indicate that it is mandatory to prepare doxorubicin calibration standard samples in biological matrices which would reflect at best the composition of samples to be analyzed. This method was successfully applied in animal studies for the analysis of effluent, serum and tissue samples collected from pigs and rats undergoing ILP.


Subject(s)
Body Fluids/chemistry , Doxorubicin/analysis , Heparin/analysis , Lung/chemistry , Lung/physiology , Perfusion/methods , Animals , Doxorubicin/chemistry , Humans , Male , Rats , Rats, Inbred F344 , Swine , Tissue Distribution/physiology
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