[Long-term survivors of advanced non-small-cell lung cancer: characterisation and prognostic factors in a retrospective study]. / Longs survivants de cancers bronchiques non à petites cellules stades IIIB-IV.

INTRODUCTION: The prognosis of non-small cell lung cancer (NSCLC) is poor, especially for advanced stages IIIB-IV. Clinical experience shows that the evolution of the disease is heterogeneous. A small number of patients survive more than 2 years after diagnosis; they are called long term survivors (LS). The aim of our study was to characterise this subgroup of patients. METHODS: A retrospective study in the respiratory department of a general hospital including all patients with a proven diagnosis of NSCLC stage IIIB and IV. RESULTS: 169 patients were included (43 females). There were 13.6% LS. Two thirds of the patients were PS 0-1, 84.6% were stage IIIBw-IV. Adenocarcinoma was the predominant histological type. Univariate analysis revealed that long term survival was associated with a Charlson's score < or = 2, PS 0-1, a normal white blood cell count at diagnosis, adenocarcinoma histology, response (RP) to first line treatment and treatment with a tyrosine-kinase inhibitor (TKI). In multivariate analysis only PS 0-1, RP and treatment with a TKI were independent factors for longer survival. CONCLUSION: LS exist and represent 13.6% of our patients. TKI appear to offer new opportunities for these patients.

[Lung cancer in the elderly: performance status and/or geriatric indices?]. / Cancer bronchique du sujet âgé: performance status et/ou indices gériatriques?

INTRODUCTION: Demographic aging poses a problem of management in patients over 65 years old with lung cancer (LC). Performance status (PS) is an index of global activity that, in part, determines treatment. Geriatric indices allow a multifactorial assessment of the elderly subject. The aim of our study is to evaluate whether PS correlates with the geriatric indices in elderly patients with lung cancer. METHODS: In a single centre prospective study the geriatric indices (ADL, IADL, PINI, MMS) and the Charlson score (CS) were measured before treatment. RESULTS: Forty one patients aged 75.7 +/- 6.6 years were included in the study. PS 3-4 was found in 15% of patients and 44% had stage IV disease. Half of them were ADL dependent and 95% were IADL dependent. A MMS<24 was found in 29% and 17% had a PINI > 20. The CS was 2.7 +/- 2.1. There was a correlation between PS and the geriatric indices but no correlation between PS and CS. CONCLUSION: PS is significantly correlated with the geriatric indices but is independent of CS. PS appears to be a good parameter for the assessment of global activity in the elderly subject with LC.

["Post traumatic" leptospirosis complicated by acute respiratory insufficiency]. / Leptospirose ictéro-hémorragique << post traumatique >> compliquée d'insuffisance respiratoire aiguë

INTRODUCTION: Leptospirosis is a rare cause of alveolar haemorrhage. The diagnosis is often delayed particularly when the mode of infection is atypical. These serious complications require prompt antibiotic treatment. CASE REPORT: A 21-year-old man was involved in a road accident and found lying unconscious in a roadside ditch containing stagnant water. Ten days later he presented with bilateral interstitial pneumonia and rapidly increasing hypoxaemia associated with cholestasis and liver cell necrosis. Broncho-alveolar lavage revealed alveolar haemorrhage. There was satisfactory resolution following antibiotic therapy. CONCLUSIONS: The diagnosis of leptospirosis was considered initially despite negative serology (Martin and Petit) and confirmed by sero-conversion 20 days after the onset of symptoms.

Oral moxifloxacin vs high-dosage amoxicillin in the treatment of mild-to-moderate, community-acquired, suspected pneumococcal pneumonia in adults.

STUDY OBJECTIVES: Comparison of the efficacy and safety of moxifloxacin vs amoxicillin for treatment of mild-to-moderate, suspected pneumococcal community-acquired pneumonia (CAP) in adult patients. DESIGN: Multinational, multicenter, double-blind, randomized study. SETTING: Eighty-two centers in 20 countries (Argentina, Brazil, Chile, Croatia, Czech Republic, Estonia, France, Hong Kong, Hungary, Lithuania, Mexico, Portugal, Russia, Slovenia, South Africa, Spain, Turkey, Ukraine, United Kingdom, and Uruguay). PATIENTS: Four hundred eleven adults (inpatients or outpatients) with suspected pneumococcal CAP. INTERVENTIONS: Randomization 1:1 to moxifloxacin, 400 mg/d, or amoxicillin, 1,000 g tid, for 10 days. RESULTS: Primary efficacy parameter was clinical response, 3 to 5 days after therapy (end of therapy [EOT]) in the per protocol (PP) population (362 patients). The clinical success rate in the PP population was 91.5% (moxifloxacin) and 89.7% (amoxicillin; two-sided 95% confidence interval, -4.2 to 7.8%). The clinical cure rate in patients with proven pneumococcal pneumonia was similar in both treatment groups (87.8%). The bacteriologic success rate in 136 bacteriologically evaluable patients at the EOT was 89.7% (moxifloxacin) and 82.4% (amoxicillin). The bacteriologic success rate against Streptococcus pneumoniae was 89.6% (moxifloxacin) and 84.8% (amoxicillin). The frequency of adverse events was comparable in both treatment groups. Digestive symptoms were the most common drug-related adverse events in both treatment groups. CONCLUSIONS: Moxifloxacin was statistically at least as effective as high-dose amoxicillin for treatment of mild-to-moderate, suspected pneumococcal CAP. Moxifloxacin may be an alternative for empiric CAP treatment, especially in areas where multidrug resistance in S pneumoniae is sufficiently prevalent to preclude routine penicillin.

[Gastric volvulus associated with Zenker's diverticulum: a rare cause of recurrent pneumopathy]. / Volvulus gastrique associé à un diverticule de Zenker: une cause rare de pneumopathie récidivante.

We report on a case of a patient with recurrent pneumonia related to a pharygo-esophageal (Zenker's) diverticulum associated with a chronic thoracic gastric volvulus. Mechanism, diagnosis and treatment of this rare disease are discussed.

[Mycoplasma pneumoniae pneumopathy. 10 cases]. / Pneumopathie à Mycoplasma pneumoniae. 10 observations.

OBJECTIVES: Describe the different features of a common disease: Mycoplasma pneumoniae pneumonia. PATIENTS AND METHODS: The hospital files of 10 consecutive patients with microbiologically proven Mycoplasma pneumoniae pneumonia were reviewed retrospectively. These 10 patients were hospitalized over a 15-month period among 150 patients admitted to the Versailles general hospital for community-acquired pneumonia. We compared our series with data in the literature. RESULTS: Most of the patients with Mycoplasma pneumoniae pneumonia were young apparently healthy adults. A bronchial risk factor (smoking, allergy) was however found in 60% of the patients. The principle symptom was persistent cough (100%), with fever and joint pain, or sometimes headache and signs of ENT involvement. Dyspnea was frequent, related more to associated bronchospasticity than to the severity of the pneumonia. Radiographic findings were quite variable. In one case hemolytic anemia and cold agglutinins suggested the diagnosis. Certain diagnosis was based on positive serology after hospitalization due to the long delay between symptom onset and hospitalization. The prehospital period was characterized by a succession of ineffective empirical antibiotic regimens. In routine practice, macrolides or fluoroquinolones administered for 2 to 3 weeks are the empirical antibiotics of choice. Outcome is generally favorable with rapid clinical and radiological improvement. Antibiotic therapy is not however sufficient alone to achieve improvement in the respiratory impairment: bronchodilators and corticosteroids are necessary to treat the bronchospasticity. CONCLUSION: Despite the benign nature of community-acquired pneumonia due to Mycoplasma pneumoniae, clinical manifestations, particularly bronchial inflammation may have important consequences.

Bacteriological eradication of Streptococcus pneumoniae from patients with acute exacerbations of chronic bronchitis: cefuroxime axetil versus cefixime.

The bacteriological eradication rates of Streptococcus pneumoniae from sputum of patients experiencing acute exacerbations of chronic bronchitis (WHO definition) have been compared following therapy with either cefuroxime axetil 250 mg b.d. or cefixime 200 mg b.d. All patients were hospitalised for an acute exacerbation of chronic bronchitis. The study design was a multicentre, double-blind, randomised, parallel group with patients giving written informed consent initially. Patients were recruited to the study if they met the WHO definition of chronic bronchitis, were aged 30-75 years and had a high probability of S. pneumoniae infection based on initial sputum Gram stain. All S. pneumoniae isolates were serotyped and susceptibility tested at the National Reference Centre, Paris. S. pneumoniae was eradicated more rapidly following cefuroxime axetil administration than after cefixime and this difference was statistically significant (p = 0.002) at 2-4 days post-treatment. Clinical endpoints showed a similar trend--94% response to cefuroxime axetil compared with 71% response to cefixime (RR 6.39:1). Cefuroxime eradicated S. pneumoniae significantly more rapidly than cefixime and patients in the cefuroxime axetil arm had favourable clinical criteria. The data suggest that focused antibacterial studies may be helpful in evaluating antibiotics in acute exacerbation of chronic bronchitis.

[Pulmonary embolism. Risk factors of venous thromboembolic disease]. / Embolie pulmonaire. Facteurs de risque de la maladie thrombo-embolique veineuse.

RISK FACTORS: Management of deep venous thromboembolism both in terms of diagnosis and therapeutic and prophylactic strategies has been greatly improved by advances in knowledge of the main acquired and intrinsic risk factors. RESISTANCE TO ACTIVATED PROTEIN C: This is by far the most frequent coagulation disorder predisposing to venous thromboembolism. Other intrinsic factors favoring thrombus formation (anti-thrombin II, protein C or protein S deficiencies) are much more uncommon. Laboratory tests in search for these anomalies are indicated essentially for patients who develop repeated episodes of venous thrombus formation. PROPHYLAXIS: Excepting specific cases, anticoagulant prophylaxis is not indicated in any of these anomalies beyond the usual treatment of a first episode. Among the risk factors for acquired deep vein thromboembolism, only surgery and certain obstetrical indications have been investigated sufficiently to define validated prophylaxis strategies. For medical risks, the benefit of anticoagulant prophylaxis has been demonstrated in certain disease states such as cancer, antiphospholipid syndrome and the acute phase of myocardial infarction although no widely accepted strategy has yet been established.

Western blot analysis of antibody response to pneumococcal protein antigens in a murine model of pneumonia.

To detect new antigen candidates for serological tests, we studied the antibody response to pneumococcal protein antigens in mice infected intratracheally with various Streptococcus pneumoniae strains. Sera were tested by Western blotting against whole-cell protein extracts. Mice developed a detectable immunoglobulin G-type response against a small number of polypeptides. The antibody response was strain dependent: sera from individuals infected with the same strain gave similar banding patterns on immunoblots. The banding patterns varied with the strain used for infection. However, a band at 36 to 38 kDa was recognized by all reactive sera. This band appeared to correspond to a polypeptide that was antigenically well conserved among the different S. pneumoniae serotypes. An antibody response to this antigen developed in mice irrespective of the capsular type, the virulence, and the susceptibility to penicillin G of the infecting strain. Thus, this 36- to 38-kDa protein antigen may be of value for the development of a serological test for humans.

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.

Clinical significance of the pulmonary vasodilator response during short-term infusion of prostacyclin in primary pulmonary hypertension.

BACKGROUND: The short-term vasodilator response to prostacyclin (PGI2) in patients with primary pulmonary hypertension (PPH) is not only unpredictable but also extremely variable in magnitude. In this retrospective study, we attempted to evaluate in a nonselected population of patients with PPH the degree of vasodilatation achieved during short-term infusion of PGI2 and to investigate whether patients with PPH differed in terms of baseline characteristics and prognoses, according to the level of vasodilatation achieved during initial testing with PGI2. METHODS AND RESULTS: Between 1984 and 1992, 91 consecutive patients with PPH underwent catheterization of the right side of the heart with a short-term vasodilator trial with PGI2 (5 to 10 ng.kg-1.min-1). According to the level of vasodilatation achieved during PGI2 infusion, patients were divided into three groups: nonresponding (NR, n = 40), moderately responding (MR, n = 42), and highly responding (HR, n = 9) patients. All three groups were defined by a decrease in total pulmonary resistance index (TPRi) of < 20%, between 20% and 50%, and > 50%, respectively, relative to control values. Prolonged oral vasodilator therapy was subsequently started only in MR and HR patients. All patients had long-term oral anticoagulant therapy. The survival rate at 2 years (transplant recipients excluded) was significantly higher in HR patients compared with NR and MR patients (62% versus 38% and 47% survivors, respectively; P < .05). Comparisons between groups showed no significant differences in baseline hemodynamics or clinical characteristics except for a longer time between onset of symptoms and diagnosis (ie, first catheterization) of PPH in HR patients than in NR and MR patients (71 +/- 61 versus 35 +/- 34 and 21 +/- 21 months, respectively; P < .05). CONCLUSIONS: In this study, patients with PPH exhibiting a decrease in TPRi > 50% during short-term PGI2 challenge at the time of diagnosis had longer disease evolutions and better prognoses than patients with a lower vasodilator response.

[Management of bronchial infectious episodes in general medicine]. / Prise en charge des épisodes infectieux bronchiques en médecine générale.

BACKGROUND: Acute bronchitis and chronic obstructive pulmonary disease exacerbations are frequent reasons for consultation with a general practitioner (GP). Since no consensus exists about the use of antibiotics in such indications and little is known about the use of pulmonary function tests in general practice, our objective was to describe GP's attitudes and prescription habits when faced with patients suffering from acute bronchitis (AB) or chronic bronchitis (CB) exacerbation. METHODS: The GPs participating in public health surveillance through the "réseau Sentinelles" (French Communicable Diseases Network) in March 1993 answered a postal questionnaire. This questionnaire collected their clinical attitude and prescriptions for 7 clinical cases of varying severity. RESULTS: 430 (94.7%) of the GPs answered the questionnaire. Of these more than 95% prescribed antibiotics in all the clinical cases, including for common acute bronchitis. Wide spectrum penicillins and macrolides were prescribed significantly less often as the past history increased in severity, whereas tetracyclins and oral cephalosporins were prescribed significantly more often in severe cases. Fluoroquinolones were nearly exclusively reserved for the treatment of advanced CB. Smoking cessation was systematically advised by the GPs. Faced with AB and a smoking history, 44.2% of the GPs prescribed a chest x-ray. In the case of repeat episodes of winter bronchitis, more than 70% of them evoked the diagnosis of CB. 98.% of the GPs had easy access to pulmonary function tests (PFTs) which 69.2% of the GPs prescribed as soon as CB was suspected. CONCLUSION: In the absence of a therapeutical consensus regarding bronchitis, antibiotics were prescribed virtually systematically. PFTs were not yet a routine gesture in general practice even though they were widely available and prescribed.

Increased plasma serotonin in primary pulmonary hypertension.

PURPOSE: Pulmonary hypertension can occur in patients who have disorders associated with altered platelet serotonin storage, including collagen vascular disease and platelet storage pool disease. We tested the hypothesis that primary pulmonary hypertension (PPH) may be also associated with impaired handling of serotonin by platelets, resulting in increased plasma serotonin levels. PATIENTS AND METHODS: We used radioenzymatic assays to measure serotonin in platelets and plasma and serotonin released during in vitro platelet aggregation in 16 patients with PPH, and in 16 normal controls matched for age and sex. Six patients were restudied after heart-lung transplantation to determine whether serotonin abnormalities persisted after pulmonary arterial pressure returned to normal. RESULTS: Patients had decreased platelet serotonin concentration (1.8 +/- 0.6 x 10(-18) mol/platelet versus 3.2 +/- 0.2 x 10(-18) mol/platelet in controls; P < 0.01) and increased plasma serotonin concentration (30.1 +/- 9.2 x 10(-9) mol/L versus 0.6 +/- 0.1 x 10(-9) mol/L in controls; P < 0.001). Serotonin released during in vitro platelet aggregation was higher in patients than in controls. After heart-lung transplantation, platelet serotonin concentrations remained decreased and plasma levels remained increased. CONCLUSIONS: Abnormal handling of serotonin by platelets leading to an increase in plasma serotonin occurs in PPH. The persistent decrease in platelet storage of serotonin after heart-lung transplantation suggests that this platelet abnormality is not secondary to PPH.

[Pulmonary arterial hypertension of chronic thromboembolic origin; therapeutic indications]. / Hypertension artérielle pulmonaire d'origine thrombo-embolique chronique; indications thérapeutiques.

Chronic thromboembolic pulmonary hypertension is a rare complication of acute pulmonary embolism. The therapeutic approach to the disease is addressed, based on a series of 81 patients referred to our department between 1984 and 1993. Medical treatment associates long-term anticoagulant therapy and, in some cases, inferior vena cava interruption. Two surgical procedures are available in selected patients: lung transplantation and pulmonary thrombo-endareterectomy. Lung transplantation has been performed in 8 patients since 1988 with 6 survivors with a maximal follow-up of 5 years. Twelve patients underwent pulmonary thromboendareterectomy with in 9 patients a dramatic functional and haemodynamic improvement. Chronic thromboembolism should be systematically investigated as the cause of pulmonary hypertension considering that in selected cases, curative surgery is possible.

Pulmonary hypertension in patients with human immunodeficiency virus infection. Comparison with primary pulmonary hypertension.

BACKGROUND: Previously reported cases of patients with pulmonary hypertension (PH) and human immunodeficiency virus (HIV) infection are poorly documented regarding baseline hemodynamics and potential for pulmonary vasodilatation. The purpose of this report was to compare HIV-infected patients who had PH with non-HIV-infected patients who had primary pulmonary hypertension (PPH) in terms of (1) clinical characteristics, (2) hemodynamics in baseline conditions and during a short-term vasodilator trial with epoprostenol, and (3) survival. METHODS AND RESULTS: Between April 1987 and August 1992, 20 HIV-infected patients with PH and 93 non-HIV-infected patients with PPH were referred to our department. At the time of referral, baseline right-side heart hemodynamics were obtained in addition to demographic variables and medical history. A short-term vasodilator trial with epoprostenol was performed in 19 of 20 HIV-infected and 86 of 93 non-HIV-infected patients. Outcome and survival were analyzed and compared for both groups (22 transplant recipients were excluded from the group of patients with PPH). At the time of diagnosis of PH, HIV-infected patients significantly differed from non-HIV-infected patients in age (32 +/- 5 versus 42 +/- 13 years; P < .05) and degree of disability (New York Heart Association functional class III or IV, 50% versus 75%; P < .01). The proportion of disease states known to be associated with PPH (Raynaud's phenomenon, migraine, collagen disease without overt symptoms and signs, or a positive family history of PPH) was similar in the two groups. HIV-infected patients had a severe but significantly lower level of PH than patients with PPH. The percentage of responders to epoprostenol and the level achieved in pulmonary vasodilatation were similar in the two groups. PH was the cause of death in 8 of the 10 HIV-infected patients who died within 1 year after the diagnosis of PH. Overall survival was poor and not significantly different between the two groups. Pathological findings in lung tissue obtained from 3 HIV-infected patients were close to those seen in most of the lung specimens available from 27 patients with PPH and resembled plexogenic pulmonary arteriopathy. CONCLUSIONS: These results support the view that HIV infection may now be regarded as another common disease state that can be associated with PPH development. The lower initial severity in HIV-infected patients may be due to the close medical attention usually devoted to such patients, who may account for an earlier diagnosis. However, the overall survival rate of HIV-infected patients with PH appeared to be as poor as in non-HIV-infected patients with PPH.