Two-scale analysis of a tight gas sandstone.

Tight gas sandstones are low porosity media, with a very small permeability (i.e., below 1 mD). Their porosity is below 10%, and it is mainly composed of fine noncemented microcracks, which are present between neighboring quartz grains. While empirical models of permeability are available, their predictions, which do not compare well with macroscopic measurements, are not reliable to assess gas well productivity. The purpose of this work is to compare the permeability measured on centimetric plugs to predictions based on pore structure data. Two macroscopic measurements are performed, namely dry gas permeability and mercury intrusion porosimetry (MIP), together with a series of local measurements including focused ion beam and scanning electron microscopy (FIB-SEM), x-ray computed microtomography (CMT), and standard two-dimensional (2D) SEM. Numerical modeling is performed by combining analyses on two scales, namely the microcrack network scale (given by 2D SEM) and the individual 3D microcrack scale (given by either FIB-SEM or CMT). The network permeability is calculated by means of techniques developed for fracture networks. This permeability is proportional to the microcrack transmissivity, which is determined by solving the Stokes equation in the microcracks measured by FIB-SEM or CMT. Good correlation with experimental permeability values is only found when using transmissivity from 3D CMT data.

Age and prognosis of non-small cell lung cancer. Usefulness of a relative survival model.

The aim of our study was the comparative evaluation of a relative survival model and a Cox model to determine the prognostic factors of survival for patients with surgically cured non-small cell lung cancer (NSCLC). We focused particularly on the exact role of age in this survival. 156 patients treated between 1975 and 1988 were studied. Both univariate and multivariate analyses were performed, using the actuarial method and the Cox model for crude survival and the Hakulinen model for relative survival. This study confirmed the poor prognosis of NSCLC, even if a curative surgical procedure has been possible, with a 5-year survival of 48% for stage I tumours but only 6% for stage III tumours. The most significant prognostic factor was the postsurgical TNM staging. The relative survival method of Hakulinen dismissed age as a significant prognostic factor. Our study underlines the usefulness of relative survival methods which should be more frequently employed to allow comparisons between series of different origin and to set up multicentre therapeutic trials.

Organometallic 99mTc-aquaion labels peptide to an unprecedented high specific activity.

UNLABELLED: A new peptide labeling method that uses the organometallic aquaion [99mTc(H2O)3(CO)3]+ has been developed. METHODS: A selection of amino acids was labeled at different concentrations with the organometallic aquaion, and the labeling yield was determined by high-performance liquid chromatography. This investigation has shown histidine to be a very potent ligand, with specific activities of up to 6 TBq/micromol (160 Ci/micromol) ligand. Histidine derivatives have been coupled to neurotensin(8-13) (NT[8-13]) and have been labeled with the aquaion, resulting in high specific activities with (N(alpha)-histidinyl)acetic acid-NT(8-13) similar to those with histidine. RESULTS: Histidine derivatives of NT(8-13) labeled using this approach fully retained their receptor affinity, showing KD values of all investigated NT analogs below 1 nmol/L on colon carcinoma HT29 cells. Biodistrbution experiments in BALB/c mice showed complete clearance of (N(alpha)-histidinyl)acetic acid-NT(8-13) from the blood after 24 h and no unwanted accumulation in any tissue. CONCLUSION: The novel labeling method using the organometallic 99mTc-aquaion combines the advantage of highest specific activities with minimal functionalization of proteins and peptides under retention of biologic affinity.

D-Penicillamine-induced severe pneumonitis.

We report the first histologically described case of severe D-penicillamine-induced pneumonitis. It occurred in a 73-year-old woman who suffered from rheumatoid arthritis and had previously demonstrated gold intolerance. Pathologic study disclosed marked interstitial and alveolar damage resembling that described with certain chemotherapeutic agents. We assess the drug's responsibility, discuss possible pathogenetic pathways, and provide suggestions regarding the patient on a D-penicillamine schedule.

Relative survival analysis of 252 patients with COPD receiving long-term oxygen therapy.

OBJECTIVES: A survival analysis was conducted on patients with COPD receiving long-term oxygen therapy (LTOT) to compare two different statistical methods. METHODS: We used a multivariate crude (observed) survival model (Cox) and a multivariate relative survival model (Hakulinen). Only the latter is able to correct the survival by adjusting it to the normal life expectancy of the studied patients. PATIENTS: Two hundred fifty-two hypoxemic COPD patients (207 male) requiring LTOT were included. Mean PaO2 was <50 mm Hg before oxygen therapy. Mean age was >69 years (SE: 9.9). They had severe bronchial obstruction: mean FEV1 was <33% (10.6) of predicted values, with some CO2 retention: mean PaCO2 was 45.6 (7.1) mm Hg. By December 31, 1995, 189 patients had died (75%) and 13 (5%) were unavailable for follow-up. RESULTS: The overall crude survival was poor: 80.9% after 1 year, 67.1% after 2 years, 34.7% after 5 years, and 7.1% after 10 years. In the crude multivariate analysis (Cox), the negative prognostic factors were age and hypercapnia. The overall relative survival (Hakulinen), corrected for life expectancy, was 82.8% after 1 year, 70.8% after 2 years, 41.5% after 5 years, and 10.25% after 10 years. In the final multivariate relative model, age was no longer significant and the only bad prognostic factor was hypercapnia with a relative risk of 1.97 (1.16 to 3.34). CONCLUSION: This work shows the inadequacy of the Cox observed survival model when it comes to appreciating the real prognostic impact of age, because of the confusing factor associated with a normal life expectancy.

Nasal intermittent positive pressure ventilation. Long-term follow-up in patients with severe chronic respiratory insufficiency.

Prior studies have shown that nasal intermittent positive pressure ventilation (NIPPV) can improve arterial blood gas values, prevent symptoms resulting from alveolar hypoventilation, and decrease hospitalization in patients with chronic respiratory failure. Most studies have involved small samples of patients followed up for a limited time. This study reviews our experience during 5 years use of NIPPV in 276 patients with kyphoscoliosis, posttuberculosis sequelae, Duchenne-type muscular dystrophy, COPD, and bronchiectasis followed up for > or = 3 years while receiving NIPPV. Outcomes were compared for patients who survived short term eg, died or converted to management with a tracheostomy and intermittent positive ventilation (TIPPV) during year 1 or year 2 on a regimen of NIPPV and long term, eg, survived more > or = 2 years on a regimen of NIPPV. The most favorable outcome was achieved by patients with kyphoscoliosis and posttuberculosis sequelae with improvement in PaO2 and PaCO2 (p < 0.0001) and a reduction in days of hospitalization for respiratory illness (p < 0.0001) for > or = 2 years while receiving NIPPV. Patients with Duchenne-type muscular dystrophy also had fewer hospital days during NIPPV (p < 0.003) but only 9 of 16 patients (56 percent) continued using NIPPV for the duration of followup. Benefit was also more short term for patients with COPD and bronchiectasis. NIPPV can sustain improvement in gas exchange, while reducing hospitalization for substantial periods of time. NIPPV can be an attractive and effective alternative to other methods of assisted ventilation such as TIPPV.

Standard combination versus alternating chemotherapy in small cell lung cancer: a randomised clinical trial including 394 patients. 'Petites Cellules' Group.

PURPOSE: to compare standard and alternating administration of chemotherapy combinations in small cell lung cancer (SCLC) patients. MATERIAL AND METHODS: in a multicenter clinical trial, 394 previously untreated SCLC patients were randomised to receive, every 4 weeks, eight courses of either a standard regimen with CCNU, cyclophosphamide, adriamycin (CCA) and VP16 or an alternating regimen (CCA regimen alternating with cisplatin-vindesine-VP16). RESULTS: overall response rate was higher in the standard group (78%) than in the alternating group (64%) (P = 0.0001). Complete response rate was also higher in the standard group (32%) than in the alternating group (18%) (P = 0.004). The median survival in the overall SCLC population was 306 days in the standard group and 272 days in the alternating group (P = 0.08). In limited SCLC patients, median survival was higher in the standard group (421 days) than in the alternating group (328 days) (P = 0.01). Grade III/IV haematological toxicity was lower in patients in the alternating group (25 versus 47%) (P < 0.001). CONCLUSION: the standard regimen was better than the alternating regimen for patients with limited forms of SCLC. The alternating regimen, associated with better haematological safety and ensuring a fairly similar survival, may be considered in patients with extensive SCLC. Pleiomorphic resistance mechanisms to chemotherapy make it difficult to define a non-cross-resistant chemotherapy regimen.

[Comparison of relative survival vs. classical survival. Apropos of primary bronchial cancer]. / Les apports de la survie relative par rapport à la survie classique. A propos du cancer bronchique primitif.

The aim of the study is to compare the usefulness of a recent relative survival model versus more classical methods for univariate and multivariate survival analysis, applied to a population of patients with surgically cured non small cell lung cancer, in determination of prognostic factors and appreciation of the exact role of age on survival. We studied 156 patients surgically treated between 1975 and 1988. Both univariate and multivariate analysis were performed, using the actuarial method and the Cox model for crude survival and the additive Hakulinen model (1985) for relative survival (total risk of death equal to natural risk of death in general population plus disease specific risk of death) which is an age-adjusted survival corrected for normal life expectancy. In addition, the loss in life expectancy was also calculated. Our 156 patients (including six females), whose age ranged from 30 to 78 (mean age 59) were almost all current or former smokers (97%) and 63% had clinical trouble. Squamous cell carcinoma was the most common histology (76%) before adenocarcinomas (20%). Pneumonectomy and lobectomy were equally performed. Post surgical TNM staging was stage I = 78 (50.3%), II = 23 (14.8%), IIIa = 44 (28.4%), IIIb = 10 (6.5%). By 31 December 1990, 116 patients had died, 24 were alive and 16 lost to follow-up. In univariate analysis, overall survival is (crude/relative): 1 year (75.8%/77.5%), 2 years (53.8%/56.0%), 5 years (28.7%/32.5%), 10 years (14.4%/18.9%). Univariate prognostic factors are histopathology, surgical procedure and post operative TNM staging. The overall loss in life expectancy is 71.4% (5.5 years of life expectancy vs 19.21). The loss is higher for the younger patients than for the older ones (73% for the 30-49 year old group--59.2% for the more than 70 year old group). In multivariate analysis, prognostic factors are: Cox model: post-surgical TNM staging, histopathology and age (RR = 2.18 [1.13-4.23] for patients over 65); Hakulinen model: TNM staging. In this model, age is no longer a significant prognostic factor. In conclusion, this study confirmed the poor prognosis of NSCLC, even if a curative surgical procedure has been possible, with a 5-year survival of 48% for stage I tumours but only 6% for stage III tumours. The most significant prognostic factor is the post-surgical TNM staging. The relative survival model of Hakulinen dismissed age as a significant prognostic factor.(ABSTRACT TRUNCATED AT 400 WORDS)

[Unexplained pulmonary edema: demonstration of obstruction to pulmonary venous return by transesophageal echocardiography. Apropos of 4 cases]. / Oedèmes pulmonaires inexpliqués: mise en évidence d'une gêne au retour veineux pulmonaire par échocardiographie transoesophagienne. A propos de quatre observations.

The usual causes of pulmonary edema are left ventricular dysfunction, mitral valve disease or left atrial myxoma. Obstruction to pulmonary venous drainage is a rare and unrecognised diagnosis which should be considered when the usual investigations are unproductive. The authors report four cases in which transesophageal echocardiography showed pulmonary edema to be due to compression of one or more pulmonary veins by a mediastinal mass (2 cases), by the false lumen of dissection of the aorta (1 case) and postoperative stenosis of the pulmonary veins (1 case). These cases underline the diagnostic value of this technique which rapidly provides diagnostic information with privileged visualisation of the pulmonary veins and abnormalities of acceleration of blood velocities in the Doppler mode due to obstruction.

[Drug-induced respiratory complications. Study of 27 cases]. / Accidents respiratoires médicamenteux. Etude de 27 observations.

Over 8 1/2 years, we observed 27 patients with drug-induced respiratory disease (DIRD). The inducer drugs were mainly those used in cardiology (9 patients, of whom 8 had amiodarone pneumonitis), in oncology (8 patients), in rheumatology (4 patients; 3 from d-penicillamine and 1 from gold), and in neurology (4 cases from ergoline derivatives). The main pattern of DIRD was a diffuse interstitial lung disease having either a rapid, a slowly progressive or a chronic course. Only the two former patterns offered clearing following withdrawal of the drug. Severe bronchiolitis obliterans from d-penicillamine (2 cases) and pulmonary eosinophilia (2 cases) was also observed. The onset of DIRD occurred earlier, i.e. following shorter periods of drug administration (months), in the acute interstitial lung disease variant, while it occurred after years of drug exposure in subacute and chronic forms. In contrast to other reports, bronchoalveolar lavage lymphocytosis was not a prominent feature in amiodarone pneumonitis. The outcome was favourable in 16 patients; deaths was encountered during the florid phase of DIRD in 3; incapacitating sequelae were noted in 6 patients, leading to subsequent death in 2; the underlying disease accounted for 7 additional deaths. Therefore, DIRD are relatively common, develop often in patients with severe underlying conditions, and interstitial pneumonitis is their pattern of predilection. Amiodarone emerges as a common inducer, and accounted for more cases than all chemotherapeutic agents grouped together in our series.

[Respiratory manifestations of hemorrhagic rectocolitis]. / Les manifestations respiratoires de la rectocolite hémorragique.

The spectrum of respiratory diseases associated with ulcerative colitis. The respiratory diseases associated with ulcerative colitis have recently been recognized, and principally affect the bronchi. Both chronic bronchitis and bronchiectasis may develop after many years, some of the patients having already undergone colectomy. Chronic bronchitis is characterized by cough and chronic mucopurulent sputum, and these symptoms may be exacerbated during acute flare-ups of ulcerative colitis. The bronchial lesions are inflammatory and can be reversed by corticosteroid therapy. Bronchiectasis produces similar symptoms, but has distinctive radiological features. Corticosteroids may sometimes reduce the symptoms, but they have no effect on the bronchial lesions. Salicylazosulfapyridine might be responsible for hypersensitivity lung diseases with eosinophilia, but the drug does not seem to be involved in the genesis of these bronchial manifestations. There have been occasional reports of other respiratory diseases associated with ulcerative colitis, including obliterative bronchiolitis, isolated and asymptomatic airflow obstruction, inflammatory tracheal stenosis, pulmonary vasculitis, pleurisy and pleuropericarditis, chronic pneumonia and interstitial fibrosis which may be diffuse or localized to the apices.

[Lympho-epithelial lesions induced by plasma cells in a pulmonary MALT lymphoma]. / Lésions lympho-épithéliales induites par des plasmocytes dans un lymphome MALT du poumon.

One case of pulmonary lymphoma of MALT origin is reported. The diagnosis was made by histological and immunohistological study of surgical specimen. Cytologically, the tumoral proliferation was made by an admixture of centrocyte-like cells, small lymphocytes and vacuolized plasma cells. Lympho-epithelial lesions were particular because induced by tumoral plasma cells. From this case, problems of diagnosis and physiopathology of pulmonary MALT lymphomas are discussed.

[COPD in elderly patients]. / Bronchopneumopathies obstructives chroniques du sujet âgé

INTRODUCTION: Patients with COPD are growing in number and are getting older, with 75% of deaths occurring after the age of 75; the proportion of women is increasing. STATE OF THE ART: There are few data regarding COPD in the elderly. The related medical and social demands are significant and rise as age and respiratory disability increase. Admission rates to hospital are increasing and, despite the development of services as alternatives to hospital admission, the portion of healthcare resources taken up by elderly COPD patients continues to rise. PERSPECTIVES: Costly therapeutic interventions for COPD should only be employed if they improve the patient's health related quality of life, which is hard to evaluate and correlates poorly with lung function parameters. Although depression is common and more often found in this condition than in others, it cannot be attributed purely to the effects of COPD. CONCLUSION: Preventive measures and new strategies towards more efficient care of elderly patients with COPD must be developed to improve quality of life and to reduce health care costs.

[COPD in elderly patients]. / Bronchopneumopathies obstructives chroniques du sujet âgé.

INTRODUCTION: Patients with COPD are growing in number and are getting older, with 75% of deaths occurring after the age of 75; the proportion of women is increasing. STATE OF THE ART: There are few data regarding COPD in the elderly. The related medical and social demands are significant and rise as age and respiratory disability increase. Admission rates to hospital are increasing and, despite the development of services as alternatives to hospital admission, the portion of healthcare resources taken up by elderly COPD patients continues to rise. PERSPECTIVES: Costly therapeutic interventions for COPD should only be employed if they improve the patient's health related quality of life, which is hard to evaluate and correlates poorly with lung function parameters. Although depression is common and more often found in this condition than in others, it cannot be attributed purely to the effects of COPD. CONCLUSION: Preventive measures and new strategies towards more efficient care of elderly patients with COPD must be developed to improve quality of life and to reduce health care costs.

[Busulfan-induced pneumopathy]. / La pneumopathie du busulfan.

Busulfan or Misulban is considered by many the treatment of choice in chronic myeloid leukemia, for which it is used as a single agent. An interstitial fibrosing lung disease occurring after Busulfan was first described in 1961 and to date 56 cases have been published and are the object of this review. The clinical picture of this drug induced disease is well characterised. The disorder has an estimated incidence of 6% and begins gradually, marked by non-specific signs (dyspnoea, cough) and by an alteration in the clinical state, often severe, and is frequently accompanied by skin pigmentation. As a rule it occurs after prolonged treatment (on average 41 months, cumulative dose 2.900 mg). The respiratory function pattern is that of an interstitial fibrosis characterised by reduced volumes and hypoxaemia and hypocapnic respiratory failure. The radiology reveals interstitial and predominantly basal shadows. The histology is often obtained, either by lung biopsy or frequently at necropsy, because the prognosis is poor with an 84% mortality from respiratory failure. As for numerous interstitial pneumopathies, it poses questions as to the pathogenesis and early detection, problems which at present are imperfectly resolved.

[Pneumopathy caused by methotrexate]. / La pneumopathie du méthotrexate.

Methotrexate, an antifolate cytotoxic drug, is used in anticancer chemotherapy as well as an immuno suppressive in rheumatoid arthritis. It is responsible for numerous secondary effects, amongst which is a characteristic acute pneumonia known since 1969. This pneumonitis has been described in detail, up to the present time in 78 cases gathered in this review. The prevalence of this complication is estimated at around 7%. This pneumonia may occur whatever the age, indication for which methotrexate is prescribed, the route of administration of the product (including the intra-thecal route) and the dose. It includes dyspnoea, fever, (sometimes quite marked) and frequently an acute reversible respiratory failure. Radiologically the opacities are usually diffuse interstitial and symmetrical with a basal predominance with sometimes some confluence and occasionally a pleural reaction. In a small number of cases a transient mediastinal adenopathy has been described. Respiratory function tests show a rapidly developing restrictive syndrome accompanied by hypoxia and hypocapnia. Broncho-alveolar lavage is characterised by hypercellularity with a frank and apparently transitory lymphocytosis. Histologically the most frequent lesion sighted is an extensive acute granulomatous reaction with or without oedema. Most often the outcome is favourable (75% of cases). However 6 deaths due to respiratory failure have been reported. Even though there has not been any formal test, steroid therapy in high dosage seems to accelerate recovery. Progress to an irreversible pulmonary fibrosis is possible but rare. The mechanism of this drug related acute pneumonia is not known but would seem to resemble that of other granulomatosis. Besides this rapidly progressive pneumonitis, methotrexate is responsible for a very small number of cases of severe pulmonary oedema and of acute painful pleurisies.

[Respiratory manifestations of hemorrhagic rectocolitis]. / Manifestations respiratoires de la rectocolite hémorragique.

Several respiratory complications have been described in patients with ulcerative colitis (UC), and are the subject of this review. Involvement of the bronchial tree is the most frequent of them. Chronic bronchitis (16 patients) and bilateral bronchiectasis (16 patients) are responsible for chronic disabling bronchial suppuration. Symptoms related to the bronchial disease most often develop in patients in whom the diagnosis of ulcerative colitis is already established (88% of cases). Occurrence before the diagnosis of UC is possible, but unusual. Bronchial involvement can develop in patients whose UC is in complete remission, or who have undergone coloproctectomy up to several years earlier. Impressive improvement of cough and sputum production commonly occur following inhaled steroids. This is of great diagnostic and therapeutic significance. Other complications include subacute asphyxiating tracheal obstruction due to intralumenal inflammatory overgrowth (1 patient), small airways disease and panbronchiolitis (2 patients), BOOP (4 patients), pulmonary angiitis (6 patients), desquamative interstitial pneumonitis and granulomatosis (2 and 3 patients respectively), biapical pulmonary infiltrates (2 patients) and serositis. In addition, UC patients can develop less specific pulmonary problems such as pulmonary edema, pulmonary embolism and sulfasalazopyridine-induced pneumonitis and fibrosis.

[Nitrosourea-induced lung diseases]. / La pneumopathie des nitrosourées.

Nitrosoureas belong to the group of alkylating agents, and are increasingly used in the treatment of brain malignancies, due to their excellent penetration through the hemo-meningeal barrier. Since 1976, pulmonary toxicity from nitrosoureas has emerged as a significant problem, especially with BCNU, and 72 cases are available in the literature for review. While it is difficult to ascertain the exact prevalence of nitrosourea lung (estimate range between 1 and 20%), it is now clear that a direct relationship exists between cumulated exposure to the nitrosourea, and the likelihood of developing pulmonary toxicity. The clinical picture is that of a diffuse, severe fibrosis with hypoxemia. Histopathology, available in 55 reports, showed diffuse bland fibrosis. The outcome is poor with 67% of the patients dead by the time of publication. While we feel that corticosteroids should be tried for any possible beneficial effect, they seem to be of limited help.

[Lung disease due to Mycobacterium xenopi excluding AIDS. Apropos of 8 cases]. / Atteintes pulmonaires à Mycobacterium xenopi en dehors du SIDA. A propos de 8 cas.

Between 1994 and early 1999, Mycobacterium xenopi was isolated in 11 HIV-negative patients seen at the Respiratory Disease Department of the Dijon University Hospital. Eight of these patients met the criteria of lung infection. Clinical and radiological features simulated pulmonary tuberculosis which delayed diagnosis until the germ was identified. Treatment is considered to be mandatory though it is difficult to manage and often disappointing. In spite of long-term medical care, sometimes associated with surgery, outcome is currently determined by the underlying disease rather than by Mycobacterium xenopi infection.

[Evaluation of the ventilatory function in elderly subjects]. / Evaluation de la fonction ventilatoire chez le sujet âgé.

OBJECTIVES: Many elderly subjects are at risk of respiratory failure due to effect of age on ventilatory system and the deleterious effects of toxins and respiratory diseases. As spirometry is the main technique currently used to detect altered ventilatory function we first used this method in very elderly subjects then compared the results with clinical measurements of chest and abdominal ampliation. METHODS: Among 65 subjects over 75 years of age, with no cardiorespiratory or neuropsychologic impairment and who had undergone spirometry and chest and abdominal ampliation measurements in 1991, 24 were re-examined in 1994 using exactly the same techniques. Forced vital capacity and maximum expiratory volume/second were measured at the patient's home with a previously calibrated spirometer. All tests were run according to the recommendations of the European Respiratory Society. Variations in upper chest, lower chest and abdominal circumferences were also recorded. RESULTS: Mean age of the subjects was 84.1 +/- 3.7 years and all spirometric tests were reproductible within a given measurement session. There was no significant difference for forced vital capacity or for maximum expiratory volume/second between the 1991 and the 1994 values with variations of 2.1 +/- 0.4 and 9.4 +/- 3.4% respectively. Four of the 24 initially asymptomatic subjects had signs of obstruction which resolved in 2 with the salbutamol and/or ipratropium bromide. The correlations between spirometric data and chest and abdominal ampliations were significative. CONCLUSIONS: Spirometry can be an effective tool in elderly patients. In addition to frequent discovery of reversible bronchial obstruction (7 to 41% according to the series), it can be used to screen for reduced ventilatory "reserve". Chest ampliations measures also appear to be simple means of determining which subjects could benefit from physical therapy aimed at improving chest and abdominal musculature.