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Biomedical subjects

P Leophonte

Publications and source records attributed to P Leophonte.

At least 19 recordsLinked to original sources

Comparative safety and efficacy of sparfloxacin in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a double-blind, randomised, parallel, multicentre study.

In a double-blind, placebo-controlled trial, patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) were randomly allocated to oral treatment with sparfloxacin (200 mg loading dose followed by 100 mg once daily) or amoxycillin/clavulanic acid (500 mg/125 mg tds) for a total treatment duration of 7 to 14 days. Patients were evaluable if they had a FEV1/FVC ratio of less than 70% at stable state and presented with a suspected infectious exacerbation defined as increases in dyspnoea, sputum volume and sputum purulence. The primary efficacy variable was the overall success (defined as disappearance or improvement of dyspnoea and reductions in sputum volume and purulence) at end of treatment and follow-up. Overall efficacy was assessed in both the intent-to-treat (728 patients) and the evaluable (351 patients) populations. At the end of treatment and follow-up, success rates were identical for the sparfloxacin (87.3% and 78.7%) and amoxycillin-clavulanic acid (88.8% and 79.8%) treatment groups. Similar figures were found for the intent-to-treat population. The analysis of drug safety was similar for both treatment groups. The most frequently encountered pathogens were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Sparfloxacin appeared superior for bacteriological eradication of Haemophilus influenzae, and Moraxella catarrhalis. Sparfloxacin in a single daily dose appears at least as effective as amoxycillin/clavulanic acid in the treatment of patients with acute exacerbations of COPD.

Acute Disease

[Nocardia respiratory infection in patients with chronic obstructive lung disease].

Pulmonary nocardiosis is a respiratory infection which is usually described in the immunocompromised. We report three cases in patients suffering from chronic airflow obstruction. In two cases there was a parenchymal disorder and in one case bronchial suppuration without involvement of the alveolar region. The diagnosis was made in all cases by bacteriological examination from specimens obtained at fiberoptic bronchoscopy. The outcome was favourable in all three cases after appropriate treatment. These observations underline the diversity of the clinical forms of respiratory nocardiosis. Furthermore, it demonstrates their possible occurrence in non-immunocompromised patients and the need to look for this germ specifically in long drawn infections. A bacteriological diagnosis is vital to start early and appropriate antibiotic therapy which should be prolonged because of the risk of recurrence and disseminated infection.

Aged

Substance P and alveolar macrophages: effects on oxidative metabolism and eicosanoid production.

The tachykinin substance P (SP) is present in lung sensory nerve endings and may be released after neurogenic stimulation. Its role in the pathogenesis of asthma is still unclear. Nevertheless, it may play a major role in airway neurogenic inflammation. Alveolar macrophages are the predominant cells of the airway space and are involved in various types of airway inflammation. We studied guinea pig alveolar macrophage response to SP and other related peptide (C- and N-terminal sequences, NK1-receptor agonist) stimulation. Alveolar guinea pig macrophages were recovered by bronchoalveolar lavage (BAL). Macrophage reactive oxygen intermediate (ROI) production was studied by luminol-dependent chemiluminescence with several concentrations of SP and related peptides. Eicosanoid synthesis after stimulation was evaluated by thin-layer chromatography (TLC) and enzyme-linked immunosorbent assay (ELISA). SP, C-terminal sequence, and NK1-receptor agonist significantly increased ROI production by alveolar macrophages (P < 0.01). NK1-agonist and C-terminal sequence modified arachidonic acid metabolism and induced a significant increase in prostaglandin (PG)D2 synthesis (211% and 66%, respectively). We concluded that SP and related peptides directly affect guinea pig alveolar macrophages by inducing the production of inflammatory metabolites.

Animals

[Azithromycin and bronchopulmonary infections].

Azithromycin is a molecule of the macrolide family, belonging to the azalides class. Several of its characteristics allow for its use in the treatment of the community-acquired lower respiratory tract infections. Commonly isolated pathogens in bronchial infections are most frequently H. influenzae, S. pneumoniae, M. catarrhalis, C. pneumoniae and M. pneumoniae, and more rarely or in the context of a particular background, S. aureus, Gram negative bacteria and L. pneumophila. MIC90 of these germs is generally low or slightly elevated, displaying an inhibitory activity of the azithromycin on these bacteria. Nevertheless, the frequency of macrolide-resistant S. pneumoniae is not negligible and this germ must be considered as inconstantly susceptible to the macrolide family. Pharmacokinetics studies evidenced from high to very high azithromycin concentrations in the pulmonary tissues, reaching values well above MIC of pathogens commonly isolated. Given the long half-life, these concentrations persist a long time after oral administration. As azithromycin concentrates much in polymorphonuclear leucocytes, they release azithromycin after having migrated into the infectious site by chimiotactism, thus allowing to increase the antibiotic concentration at infection site. These requirements have been confirmed in vivo in animal models and in clinical studies. Two experimental models on macrolide susceptible S. pneumoniae, and H. influenzae evidenced a better activity of azithromycin in comparison to other macrolides tested against these two germs.

Acute Disease

Immunostimulant effects on granulocyte functions during an acute respiratory infection.

Treatment of healthy volunteers by Ribomunyl, whether or not in association with in vitro antibiotics (amoxicillin or josamycin), has been earlier demonstrated to be an efficient stimulant of PMN functions (adhesion and migration). This second double-blind study versus placebo was performed on 17 patients with acute respiratory infections (placebo group: eight subjects; Ribomunyl group: nine subjects). Ribomunyl treatment (four days) associated with antibiotherapy (amoxicillin) induced a significant increase of PMN adhesion (p = 0.014) with no significant effect of the placebo (p = 0.30) and no significant difference between the initial level of PMN adhesion of the two groups (placebo-Ribomunyl).

Adolescent

[Should arterial hypertension in sleep apnea syndrome be stressed?].

The frequent association of sleep apnea syndrome and essential hypertension led to think of sleep apnea as an etiology of hypertension, especially as a good correlation has been found between the severity of both diseases. Moreover, treating the apnea syndrome results in a decrease of blood pressure. The aim of our study is to depict the outlines of a severe hypertensive individual with sleep apnea by comparing 9 men primarily referred to the hypertension clinic with refractory hypertension and finally found to have sleep apnea (study group) to 23 men whose diagnosis of sleep apnea was made in the pulmonary unit (controls). Fifteen of these were hypertensives. Mean age of the study group was 47 +/- 7 years vs 60 +/- 11. Controls were less overweighted: BMI = 33 +/- 6 kg/m3 vs 39 +/- 5. Mean blood pressure was 171 +/- 16/107 +/- 4 mmHg in the study group vs 157 +/- 19/92 +/- 12 mmHg in controls. Prevalence of glucose metabolism disorders was significantly greater in the study group: 6 patients with maturity onset diabetes and 3 with proven glucose intolerance, vs respectively 4 and 6 controls. Triglycerides were elevated in both groups whereas mean cholesterol was slightly above normal values. Six patients of the study group could have an echocardiogram which showed left ventricular hypertrophy (mean left ventricular mass index = 206 +/- 31 g/m2 after the Penn convention).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Thrombo-embolic disease with antiphospholipid-type serum auto-antibodies].

We report a case of thrombo-embolic disease in which we were able to detect the presence of serum antiphospholipid auto-antibodies. The existence of antiphospholipid auto-antibodies has already been described in cases of recurrent thrombo-embolism. The thrombogenic role is only partially explained, but would for the greater part be linked to an action on the fibrolytic activity of the vascular parietal wall. Amongst these antibodies one can find amongst others VDRL, antiprothrombinase and anticardiolipin. The association of other stigmata of auto immunity is not rare, especially disseminated lupus erythematosus (LED). When phospholipids are found in an isolated fashion in cases of recurrent thrombo-embolism they produce the syndrome of antiphospholipids. The long term prognosis of this syndrome has not yet been established but the risk of a secondary systemic disease developing justifies a clinical follow up and regular blood checks.

Adult

[Recurrent thromboembolism disclosing protein C deficiency. Apropos of a case with familial investigation].

Every thromboembolic manifestation, especially in young subjects, calls for an aetiological study in which haemostasis is evaluated primarily with assays of physiological coagulation inhibitors: protein C, protein S and antithrombin III. Protein C deficiency is found in 6 to 7% of thromboembolic manifestations. We report the case of a 21-year old man who had phlebitis followed by pulmonary embolism without facilitating factors. Protein C level was 50% of normal value (0.50 IU/ml). The patient received heparin, subsequently replaced by oral anticoagulants after a long period of overlap between the two treatments. The outcome was favourable. Family investigation yielded a history of thromboembolic accidents in several members of the family, some of whom were protein C deficient (50% of normal value). Protein C synthesis is vitamin K-dependent. Protein C deficiency is transmitted as an autosomal dominant trait. Normal values range from 0.65 to 1.35 IU/ml. Clinically, 25% of the patients are said to be asymptomatic. The first thrombotic accidents occur in young subjects (mean age 29 +/- 14 years). Several points emerge from this case: full evaluation must be performed, especially in young subjects; family investigation consolidates the diagnosis and enables symptomatic protein C deficient patients to be treated and thrombotic manifestations to be prevented by effective anticoagulant therapy in high-risk situations; a prolonged period of heparin-oral anticoagulant overlap is needed to avoid cutaneous necrosis.

Adult

[Amoxicillin as a 1st choice: 275 acute focal pneumopathies treated on an outpatient basis].

From December 1986 to January 1988, 100 General Practitioners and Pneumologists working outside hospital included in open unmatched series 275 patients who were diagnosed as having pneumonia at home. The study consisted of 53.2% men with an average age of 49.3 plus or minus 19.3. Their temperature on the first day (J1) was in 72.7% of cases greater than 38.5 degrees Centigrade. The doctors felt that the general state was good in 66.5% of the cases. Cough was present in 83.5% of cases but was dry in one out of every two. The patients received Amoxycillin in a dose of 2 grams per day orally (66.9%), or by injection (33.1%). On the third day (J3) 90% of the patients had a temperature below 38.5 degrees Centigrade. Their general state was improved in 94.6% of cases. The diagnosis of pneumonia at home was confirmed radiologically on 219 of the films available, confirming the good specificity of the clinical diagnosis of pneumonia at home. Ten patients were hospitalised. The apparent treatment of Amoxycillin was given in 247 cases (89.8% of cases). In 28 cases (10.2%) the treatment was changed by the addition or substitution of a Macrolide (15), or another antibiotic (5), and in 80 cases a change of treatment was not specified. 25 of these 28 cases were reviewed on the 14th day (J14) and no failures were observed after the change of treatment. In 247 patients in whom the treatment with Amoxycillin was followed 336 were reviewed on the 15th day and there had been four failures. Three were intolerant to the drug and there was one relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care

[Sarcoidosis and heredity. 3 familial cases].

It is very uncommon to find several cases of sarcoidosis in the same family. In the majority of published reports, only 2 persons are involved in each family. Genetic predisposition is probably, but its true importance as compared with environmental conditions is uncertain owing to the lack of epidemiology studies. We report 3 cases of sarcoidosis in the same family. In 2 of these cases (2 black sisters) the clinical set up was similar, consisting of multivisceral sarcoidosis involving the lung and mediastinum, the skin and the peripheral lymph nodes and muscles, with poor general condition and dependence on, or resistance to corticosteroids. Although the two sisters lived in different countries for several years and despite the 4-year age difference between them, the disease began in both cases at the age of 40 years. The history of this family is exemplarily in favour of a genetic predisposition and suggests than the penetrance of genetic transmission is underevaluated. Systematic pulmonary clinical and radiological examinations performed in the relatives of patients with sarcoidosis might provide information on the true incidence of familial cases. Studies of the genetic equipment of these familial cases would perhaps constitute a line of research aimed at determining the pathogenesis of the disease.

Adult

[Effects of cotrimoxazole on some macrophage functions: microbicide, tumoricide, production of free oxygen radicals, prostaglandins and leukotrienes].

In order to demonstrate an immunomodulating effect of cotrimoxazole, we investigated its influence on some macrophage (M phi) functions in culture: P815 tumor cells killing, Toxoplasma gondii killing, production of free oxygen radicals by luminol-dependent chemiluminescence, prostaglandins and leukotrienes secretion evaluated after incorporation of tritiated arachidonic acid. In vitro, cotrimoxazole inhibited in a dose-dependent fashion the chemiluminescence of murine resident peritoneal or guinea pig alveolar M phi. Production of prostaglandin (PG) 6-keto-F1 alpha, PGF2 alpha, and 5-hydroxyeicosatetraenoic acid by resident peritoneal M phi was also inhibited. However, PGD2 synthesis by alveolar M phi was enhanced. A second study was performed on peritoneal M phi, resident or elicited in vivo by one intra-peritoneal injection of an extract from Mycobacterium Tuberculosis membranes and obtained from mice pretreated or not by cotrimoxazole per os. Resident M phi from cotrimoxale-treated animals showed increased production of leucotriene B4 compared to M phi from controls. 6-keto-PGF1 alpha and free oxygen radicals production by elicited M phi was greatly enhanced by cotrimoxazole whereas thromboxane B2 was reduced. Finally cotrimoxazole enhanced intracellular killing of Toxoplasma gondii and cytotoxicity for tumor cells P815 by resident but not by elicited M phi. It is concluded that cotrimoxazole can modulate MO activation and some M phi functions involved in immune homeostasis. This data could help to understand why an antibiotic such as cotrimoxazole, which is known to be frequently used in immunocompromised hosts, is also efficient in Wegener's granulomatosis.

Animals

Goodpasture's syndrome with normal renal function.

Two cases of Goodpasture's syndrome with severe pulmonary haemorrhage and normal renal function are described. In spite of minor (patient 2) or even no (patient 1) biological or light microscopic signs of glomerulonephritis, immunofluorescence of immunoglobulin G (IgG) was strongly positive in a linear fashion along the glomerular basement membranes in both patients. We suggest that renal biopsy in patients with apparently idiopathic pulmonary haemorrhage may lead to an early diagnosis of Goodpasture's syndrome. It is not possible in this disease to recognize on presentation those patients who will remit spontaneously and those who will undergo severe disease. The deadly evolution for patient 1 and some cases in the literature lend support to the notion that cytostatics and plasma exchange must be added to corticosteroids, even if pulmonary haemorrhage is not active and renal function is normal at the time.

Adult

[3 cases of human syngamiasis in Guadeloupe].

The authors report the 3 first cases of human syngamosis due to Mammomonogamus sp. in La Guadeloupe (French West Indies). After a review of the papers published on the previous 79 world-wide cases, they point out that this parasitic disease is restricted to the West Indies/South America area, and discuss the problem of the contamination mode; they claim that chronic cough is a constant signal symptom which suggests syngamosis in subjects who are native from, or have travelled in the endemic area.

Adult