Biomedical subjects
Publications and source records attributed to P Diot.
Primary leiomyosarcoma of the pulmonary artery is an extremely rare tumor that is frequently misdiagnosed as chronic pulmonary embolism. In the present case, early diagnosis and location in the left pulmonary artery permitted resection by pneumonectomy with total cardiopulmonary bypass.
A meeting on nebulization held in April 1997 defined good clinical practices. Guidelines that were proposed pertained to the following: pneumatic and ultrasonic nebulizers; delivering circuit, occluded or not, the choice of the tip being done according to the disease to treat and to the drugs to be delivered; various functions, depending on the type of nebulizer; the particle size, as it will indicate which disease may be treated: between 2 and 6 microns for bronchi, between 0.5 et 3 microns for lung, > 5 microns for ear, nose and throat diseases; compatibility between the type of nebulizer and drugs. Ten drugs are currently registered in France. Nebulization has multiple clinical indications, such as asthma, cystic fibrosis, chronic obstructive pulmonary disease, Pneumocystis carinii pneumonia, acute laryngitis, and in infants, acute bronchiolitis. The prescription must be detailed, and the physician should make sure that the medical staff put it into application.
STUDY OBJECTIVES: To determine the predictive value of abnormalities on high-resolution CT (HRCT) on pulmonary disease in systemic sclerosis. PATIENTS: Fifty-two patients suffering from systemic sclerosis. DESIGN: Pulmonary disease was defined by pulmonary function test abnormalities, ie, total lung capacity (TLC) <80% of predicted value and/or diffusion of carbon monoxide (DLCO) <75% of predicted value, without any pulmonary event other than systemic sclerosis in the medical history. Patients were divided in two groups, group A with pulmonary disease (29 patients) and group B without pulmonary disease (23 patients). HRCT abnormalities were scored on whole lungs. A decision matrix was constructed to determine sensitivity, specificity, positive and negative predictive values, and false-positive and false-negative rates. A receiver operating characteristic curve was constructed to determine the best compromise between sensitivity and specificity. RESULTS: HRCT total scores were higher in group A (9.0+/-4.3) than in group B (5.0+/-2.8) (p < 0.001) and they correlated with TLC (r =-0.39, p < 0.005) and DLCO (r = -0.50, p < 0.0002). An HRCT score of 7 corresponded to the best compromise between sensitivity (0.60) and specificity (0.83), with a positive predictive value of 0.82. Taking into account a value of 10 for the HRCT score increased specificity to 1 but decreased sensitivity to 0.41. CONCLUSION: A minimum score of 7 would be required to consider HRCT abnormalities in systemic sclerosis as predictive of pulmonary disease. An HRCT score of 10 makes it possible to establish the diagnosis of lung involvement severe enough to impair pulmonary function.
Explore the source record for details and available documents.
Scintigraphic imagery is a functional image based on the difference of the in vivo concentration of injected radio-active traces as a function-of the metabolic characteristics of the tissues. A positive emission tomography (TEP) relies on an injection of substances which reflect the metabolic activity of the tissues and consist of protein renewal with 11C-methionine or glucose metabolism with F18-fluorodeoxyglucose (FTG). The imagery by TEP enables 85-90% of solitary pulmonary nodules to be detected. The degree of capture of the tracer enables some differentiation of a malignant lesion from a benign lesion which fixes less. In the assessment of the degree of extension in the mediastinal nodes of non-small cell Stage III cancers imagery by TEP has a sensitivity ads specificity which appears superior to those of computed tomography (TEM). The interpretation of the image is simplified by carrying out fusion images between TEM and TEP. The application of TEP in the research into thoracic recurrence has shown a cumulated specificity of 81% and a reliability of 91%. The imagery by TEP is only practised in a few centres. It should be developed in pulmonary pathology if the cost of the apparatus diminishes and if FTG is available. Radioscintigraphy is losing ground in the precise domain of non-small cell carcinoma although it shows up well as a technique in neuro-endocrine tumours. Few studies have shown a decisive value in the radioimmunoscintigraphic evaluation of the extension of mediastinal nodes. A gallium 67 scintigraphy has weak specificity and on account of this has been abandoned for the staging of tumours. Another approach has been isotopic imagery of macrophages but is major inconvenience is a lack of specificity. Scintigraphic studies coupled with ventilation/perfusion remains a useful pre-operative test above all in patients with chronic airflow obstruction with gross tumours at the borderline of operability.
Aerosol drug delivery is widely used by patients with asthma and chronic bronchial obstruction for beta-2 agonists and anticholinergic drugs. More recently, inhaled steroid sprays have also been introduced. The efficacy of easy to use aerosol sprays is well proven and has become an important administration route. Different models of metered dose inhalers with gas propellants or dry powder devices help improve patients compliance. Nebulizers can be used in particular situations. Aerosol administration is proposed for anti-infectious agents and for rhDNase in cystic fibrosis. Aerosol delivery of nucleotides and antiproteases are currently under evaluation. Gene therapy can also benefit from the aerosol route which may be proposed in the near future for many different types of systemic treatments. Possible drugs include cyclosporin for lung grafts, prostacyclin for primary pulmonary hypertension, insulin for diabetes or morphine in certain types of dyspnea.
Adult pleuropulmonary blastoma is an uncommon mesenchymal tumor of the peripheral lung parenchyma composed of undifferentiated cells. The differential diagnosis with Askin-Rosaï's tumor, an extrapulmonary pleuroparietal neuroectodermal tumor, may be a difficult task. We propose a similar therapeutic approach for these two malignant conditions: surgical excision associated with chemotherapy and autologous bone marrow transplant with adjuvant radiotherapy in case of recurrence. These two entities have many epidemiological, clinical, histological and immunohistochemical similarities.
This study evaluated the effectiveness of aerosolized cyclosporine as rescue therapy for refractory acute rejection in lung-transplant patients that is unresponsive to conventional therapy. Over 2 yr, nine allograft recipients with histologic evidence of persistent acute rejection and worsening pulmonary function were enrolled. Twenty-two patients with similar degrees of unremitting rejection served as historical controls. Aerosolization of cyclosporin A (300 mg in 4.8 ml propylene glycol) using an AeroTech II jet nebulizer was instituted daily for 12 consecutive days followed by a maintenance regimen of 3 d/wk. Cyclosporine and tacrolimus blood and plasma levels were maintained within therapeutic ranges throughout this trial. Efficacy was assessed by histologic grade of rejection, interleukin-6 (IL-6) mRNA expression by graft bronchoalveolar lavage cells, and pulmonary function testing before and during cyclosporine therapy. In seven patients, results were correlated to deposition of cyclosporine aerosol in the allograft(s) as measured by radioisotopic techniques. At a mean of 37 d after initiation of aerosolized cyclosporine, graft histology improved in eight of the nine patients. Cellular IL-6 mRNA expression decreased significantly in seven patients (mean IL-6/actin +/- SD, 40.96 +/- 118 versus 0.33 +/- 0.57 [p = 0.038]). Pulmonary function (FEV1), which had decreased posttransplant (over a mean of 347 d of observation) from a best value of 1.98 +/- 0.8 L to 1.59 +/- 0.6 L (p = 0.0077), improved over time (152 d) to a posttransplant value of 1.90 +/- 0.8 (p = 0.025). In the control subjects, FEV1 inexorably declined over a comparable period of observation (best posttransplant value 2.36 +/- 0.86 to 1.32 +/- 0.53, p < 0.0001). There was a strong correlation between cyclosporine deposition in the allograft and improvement in FEV1 (r = 0.900, p < 0.01). Fewer cycles of pulsed corticosteroids (1.4 +/- 0.9 versus 0.2 +/- 0.4, p = 0.011) and anti-thymocyte globulin 0.8 +/- 0.4 versus 0, p = 0.018) and reduced doses of oral prednisone (10.8 +/- 3.1 versus 6.1 +/- 4.2 mg/d, p = 0.026) were observed during treatment with aerosolized cyclosporine. Episodes of pneumonia also were reduced significantly during aerosol therapy (2.6 versus 0.95 episodes/100 d, p = 0.029). Nephrotoxicity and hepatotoxicity did not occur, and no patients withdrew from the study. Aerosolized cyclosporine appears to be safe and effective therapy for refractory acute rejection, but confirmation by a larger, randomized trial is necessary. The correlation observed between deposition of cyclosporine aerosol and physiologic improvement of lung function suggests that there is a dose-response relationship between the concentration of cyclosporine in the allograft and immunologic tolerance.
To identify factors influencing lung dose of aerosolized recombinant human deoxyribonuclease (rhDNase I), we used gamma camera and filter techniques to measure deposition in 15 clinically stable patients with cystic fibrosis (CF) (five males and 10 females, age 6-31 yr, mean 16.9) who were on chronic daily therapy. Total and regional deposition were correlated with breathing pattern, pulmonary function, demographic factors, and disease severity. In addition, the effects of each patient's measured lung dose on pulmonary function was estimated by stopping the drug and observing changes in spirometry over a 2-wk follow-up period. After discontinuance of the drug, all patients reported worsening of dyspnea and difficulty producing sputum. There was a significant decrease in FEV1 (% predicted, mean +/- SE, 86.9% +/- 5.57 to 77.8% +/- 5.73, p < 0.005), but all patients completed the study. In some patients, as much as 48% of the deposited aerosol was found in the pharynx (range 0.0 to 0.30 mg, mean 0.089 mg +/- 0.029), and pharyngeal deposition correlated negatively with tidal volume (r = -0.696, p < 0.006) and age (r = -0.743, p < 0.005). For the lungs, deposition ranged between 0.16 mg and 0.78 mg of the 2.5 mg nebulizer dose (mean 0.47 +/- 0.04 mg) and correlated negatively with FEV1 (% predicted, r = -0.611, p = 0.0152). However, the spirometric decrements following cessation of therapy did not correlate with the lung dose of the drug. Analysis of regional deposition within the lungs indicated a wide range of distribution between central and peripheral zones. In conclusion, the deposition pattern of rhDNase I aerosols in patients with CF is largely influenced by respiratory physiology, which itself depends upon age and severity of lung disease. As the patients grow there is a decrease in upper airway deposition and more particles are presented to the lungs where those patients with more airways disease have enhanced pulmonary deposition. Upper airway deposition of rhDNase I is significant, especially in younger patients, and may be related to laryngeal side effects.
Colistin aerosols are frequently administered to patients with cystic fibrosis. However, questions arise concerning the effect of both jet and ultrasonic nebulizers on the properties of the drug. The aim of this study was to characterize the anti-Pseudomonas aeruginosa (PA) activity of colistin after jet (Pari LL) and ultrasonic (DP100) nebulization. A bench study was performed by capturing the aerosols, determining the drug mass, and assessing its anti-PA activity. Because the inhaled mass of colistin had to be entirely recovered for the bacteriological study, it was assessed by isotopic methods, mixing the drug with a 99mTc-labelled tracer and demonstrating that 99mTc activity accurately predicted the mass of colistin. Colistin was extracted from the filters and its antibiotic activity was determined using the method employed for the study of the bacteriostatic and bactericidal power of serum on the ATCC 27853 PA strain. The postnebulization minimum inhibitory concentrations (MIC) were 1.9 micrograms.mL-1 with DP100 and 0.5 microgram.mL-1 with Pari LL. These values were less than two dilutions different from the 1 microgram.mL-1 MIC of non-nebulized colistin. We conclude that neither jet nebulization nor ultrasonic nebulization alter the antibiotic properties of colistin and that both systems can be used to nebulize colistin.
Colony-Stimulating Factors (CSFs) are a family of glycoproteins that are required for the proliferation and differentiation of hematopoietic progenitor cells. Among these factors, G-CSF and GM-CSF are principally involved in the production of neutrophils. They have been demonstrated to be effective in correcting neutropenia during cytotoxic chemotherapy or bone marrow transplantations. Beside their hematopoietic action, recent data indicate that G-CSF and GM-CSF also have stimulatory effects on mature neutrophils function. The functional properties of neutrophils that are enhanced by G-CSF and GM-CSF are those related primarily to the host's defense against microorganisms. For Gm-CSF those stimulatory effects also concern the macrophages. Investigations of several animal models of severe bacterial infection and specially pneumonia have indicated that exogenous recombinant G-CSF or GM-CSF can significantly enhance host defenses and improve rates of survival. Trials of recombinant G-CSF in combination with antibiotics for the treatment of severe pneumonia in noneutropenic patients have recently been initiated. First results confirm the good tolerance of recombinant G-CSF. Further prospective studies are required to determine the effectiveness and the conditions of administration of G-CSF and GM-CSF in this indication.
The frequency and severity of pneumococci infections, the isolation of invasive serotypes and the fact that certain serotypes develop cross-resistance to antibiotics constitute justifications for anti-pneumococci vaccination. A 23-valence vaccine (Pneumo 23) has been marketed since 1983. A meta-analysis of 9 randomized studies concluded that anti-pneumococci vaccination reduces the overall incidence of pneumococci pneumonia with bacteremia. The efficacy of the vaccine was demonstrated on 4 parameters: proven pneumococci pneumonia, proven pneumococci pneumonia and serotypes contained in the anti-pneumococci vaccine, presumed pneumococci pneumonia, presumed pneumococci pneumonia and serotypes contained in the anti-pneumococci vaccine. The efficacy of the vaccine was significant only for low-risk subjects. The protective effect was not demonstrated against pneumonia whatever the cause and against bronchitis. Other case-control or retrospective studies have also been reported. The results have been somewhat contradictory but there is a demonstration of the usefulness of vaccination in patients over 65 years of age with a moderate risk (living in institution, obstructive bronchopneumonary disease, heart failure). Vaccination is advocated not only after splenectomy and in subjects with sickle cell anemia, but also in frequently hospitalized subjects, particularly those with respiratory failure and smokers. Vaccination is also recommended in case of nephrotic syndrome or an osteomeningeal breach. In at-risk children under 2 years of age, antibiotic prophylaxis is recommended in association with vaccination. The data of revaccination is not clearly determined.
Thyomas are benign or malignant lymphoepitelial tumors often associated with parathymic syndromes. A 74-year-old subject developed a recurrent thyoma over 15 year with bronchial dilatations and repeated bronchopulmonary and sinus infections. This clinical presentation suggests Good's syndrome which combines thyoma, bronchial dilatations and hypogammaglobulinemia.
With aerosolized administration of medicines, direct access to the lung is possible. Depending on the intrapulmonary behavior of each molecule, the aerosol mode of administration makes possible either a pulmonary topical action or a systemic action, thanks to the lung's wide vascular network. An inhaled molecule's pulmonary behavior is not predictable and must be studied on its own. Some medicines with a systemic aim have a topical effect after aerosol administration: furosemide, amiloride, morphine, interferons, cyclosporin and prostacyclin. Other medicines have systemic effects after aerosol administration: insulin, growth hormone, LHRH, calcitonin and nicotine. Heparin can be classified in either group depending on the dose and type of use.
Explore the source record for details and available documents.
BACKGROUND: Community acquired pneumonia is the most common cause of death from infectious disease both in western and developing countries. A study was carried out in Conakry, Republic of Guinea and Tours, France in order to compare signs, symptoms, severity of illness, risk factors, and clinical outcome of community acquired pneumonia in adult patients admitted to hospital. METHODS: The study was performed in the cities of Conakry and Tours over the same one year period. Patients with nosocomial pneumonia, tuberculosis, and those who were HIV positive were excluded. Data were recorded on the same forms in both centres. A severity score was calculated according to American Thoracic Society criteria. Follow up was evaluated at days 2, 7 and 15. RESULTS: A total of 333 patients (218 from Conakry, 115 from Tours) were included in the study with a diagnosis of community acquired pneumonia, with or without lung abscess or pleural effusion. Mean age was higher and pre-existing illness rate, dehydration, agitation, and stupor were more frequent in patients in Tours. Respiration rates of > 30 breaths/min and the incidence of crackles were identical in the two centres. Fever above 39 degrees C, initial shock, chest pain, and herpes were significantly more frequent in Conakry. Initial chest radiographic abnormalities were similar in the two groups, ranging from unilateral pleuropulmonary involvement (89% and 83% in Conakry and Tours, respectively) to diffuse patchy parenchymal disease. Parapneumonic effusion was present in 17% and 16% of the patients of Conakry and Tours, respectively. Pneumonia was considered to be severe in 33% and 42% of the patients, respectively. In Conakry first line antibiotic therapy was penicillin alone (2 million units a day) for 197 patients (90%) and second line antibiotic therapy was prescribed for 25 patients (12%). In Tours first line therapy consisted of a single antibiotic (amoxicillin, third generation cephalosporins) for 65 patients (57%) and second line antibiotic therapy was prescribed for 55 patients (48%). The clinical outcome was similar in Conakry and Tours: 88% and 85% of patients, respectively, were afebrile or clinically cured at day 15. The mortality rate was similar (6% and 8%, respectively). CONCLUSIONS: The problems encountered in the management of community acquired pneumonia are quite different in western and developing countries. This study shows that low doses of penicillin can cure 90% of African patients with pneumonia as effectively as more aggregative treatments in European patients who are both older and have greater comorbidity. Although pneumococci with reduced penicillin sensitivity occur in western countries, this does not seem to be the case in black Africa. For these reasons, low doses of penicillin or amoxicillin remain good first line treatment.
Explore the source record for details and available documents.