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Biomedical subjects

B Coudert

Publications and source records attributed to B Coudert.

At least 19 recordsLinked to original sources
PubMed1992

Nilutamide pneumonitis: a report on eight patients.

BACKGROUND: Nilutamide is a new, specific synthetic antiandrogen, released in several countries for the treatment of metastatic carcinoma of the prostate. Eight patients at the University Medical Centre at Dijon and affiliated referring hospitals developed reversible pulmonary opacities and respiratory symptoms while taking the drug. METHODS: Records of eight patients who developed new, otherwise unexplained chest opacities while taking nilutamide were reviewed. In each patient a careful aetiological search was made for other environmental or endogenous causes. Six patients underwent bronchoalveolar lavage, and lavage fluid was cultured. Corticosteroids were not given, unless gas exchange was compromised (two patients). RESULTS: The eight patients (all male) had had carcinoma of the prostate diagnosed on average 10.2 months earlier. All had improved with nilutamide, with a dramatic decrease of prostate specific antigen levels. Seven had received nilutamide at the recommended dosage of 150 mg/day, and one had received twice that amount. Treatment had lasted on average 113 (range 10-225) days, and the mean cumulated exposure was 21.8 (3-38) grams. The chest radiographs showed bilateral infiltrates, with no consistent topographic predilection. A restrictive lung defect was present in six patients and hypoxia in all (mean arterial oxygen tension (PaO2) 6.6 kPa). Bronchoalveolar lavage showed lymphocytosis in four patients and neutrophilia in two. The outcome was favourable in all patients after they had stopped nilutamide only (five patients), with corticosteroids (two patients) or a simple reduction of nilutamide from 300 to 150 mg/day (one patient). Recovery was associated with improvement of pulmonary function and PaO2. CONCLUSION: Nilutamide is associated with interstitial pneumonitis in about 1% of patients and appears reversible.

Aged↗
PubMed1992

Amiodarone pneumonitis. Bronchoalveolar lavage findings in 15 patients and review of the literature.

UNLABELLED: Amiodarone (Am) pneumonitis is currently a common and potentially severe adverse reaction, the accurate diagnosis of which remains difficult to establish. OBJECTIVES: To determine the contribution of bronchoalveolar lavage (BAL) in the diagnostic workup of patients suspected of having Am pneumonitis. METHODS: Diagnosis of Am pneumonitis was established on the basis of (1) development of recent symptoms and pulmonary opacities while receiving the drug, (2) exclusion of other possible causes, and (3) improvement following cessation of Am and/or steroid therapy. (4) Confirmatory changes were obtained by histopathologic examination in eight cases. BAL was performed in each patient at the time of initial evaluation. RESULTS: Am pneumonitis was diagnosed in 15 consecutive patients between 1985 and 1991. The disease was associated with significant morbidity and mortality. Six patients died; four died of Am pneumonitis. A neutrophilic BAL was found in nine patients (average PMN = 26.6 percent). A mixed pattern (lymphocytic + neutrophilic) was seen in four patients (average: Ly = 19.9 percent; PMN = 11.9 percent). Two patients had a normal BAL. No patient had a lymphocytic pattern. A low CD4+/CD8+ ratio was seen in two patients. A literature survey indicated 70 cases of Am pneumonitis with detailed information on BAL. The BAL pattern was mixed in 23 (33 percent), neutrophilic in 18 (26 percent), lymphocytic in 15 (21 percent), and normal in 14 (20 percent). No correlation was found between BAL pattern and prognosis. Also, BAL pattern was related neither to daily or total dose of Am nor to duration of treatment with Am. CONCLUSION: The cellular profile of BAL in Am pneumonitis is highly variable, and no cellular pattern of BAL seems to be predictive of a detrimental outcome or of irreversible fibrosis. Aside from excluding other illnesses, and due to its extreme variability, the contribution of BAL differential in the initial workup of patients suspected of having Am pneumonitis is limited.

Aged↗
PubMed1992

[Nitrosourea-induced lung diseases].

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.

Adult↗
PubMed1991

Pharmacokinetics and metabolism of nilutamide in the isolated rat lung.

Nilutamide (N) is a potent antiandrogen used in the treatment of diffuse carcinoma of the prostate. The drug has been implicated in a few instances of pneumonitis in man. The present studies were carried out to examine N disposition in the isolated perfused lung (IPL) from rats. Both recirculating and single-pass IPL were used. Recirculation was run for 60 min at concentrations of N ranging between 12 and 120 microM (+1 mu Ci [14C]N). Single-pass perfusions were run for 30 min (uptake, 10 min; efflux, 20 min) at inflowing concentrations ranging from 12 to 480 microM (+1 mu Ci [14C]N). Nilutamide was concentrated in the recirculating IPL, and tissue to medium ratio (T/M) ranged between 6.6 and 4.2, depending on the inflowing concentration of N (Cin). High performance liquid chromatography analysis of extracts of 60-min lung homogenates demonstrated the primary amino metabolite of N in addition to the parent compound. This indicated reduction of the nitro moiety of N by lung tissues. At 60 min and Cin = 40 microM, 17.6 +/- 4.7% of the radioactivity present in lung was accounted for by the metabolite. Perfusate samples contained low to undetectable amounts of the metabolite. No metabolism of N was detected in single-pass IPL, possibly because of the shorter duration of experiments. Amount of N taken up in lung and T/M were similar to those found in recirculating preparations. Uptake of N in the single-pass IPL was proportional to N concentration up to 480 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Androgen Antagonists↗
PubMed1991

[Respiratory manifestations of hemorrhagic rectocolitis].

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.

Bronchial Diseases↗
PubMed1991

[Reflections on the management of suspected recent pulmonary embolism].

Pulmonary Embolism (EP) remains a major challenge for the physician, despite increasingly sophisticated investigations and efficient therapeutic programs. Many reasons explain persistent difficulties: the disorder crosses all specialties. A wide variety of clinical presentations has to be considered according to the size of the thrombus, the coexisting conditions ("predisposing factors") and the prior cardio pulmonary status. Major investigations include perfusion and ventilation lung scans, pulmonary angiography, invasive and non invasive investigations of the deep venous system. But obvious practical limitations exist; selection of the most suitable test includes severity of the present patient condition and risk of an early recurrence of EP; risk of the contemplated therapeutic procedure if the diagnosis of EP is confirmed; skillfulness required for the selected investigation. Angiography is mandatory if a substantial hemorrhagic risk exists, if massive EP is suspected, and if at risk treatment procedures are contemplated. In the other cases, and in the absence of significant pulmonary pathology, a lung perfusion scan is the advisable procedure; the diagnosis is excluded if the scan is normal. Previous or current significant pulmonary pathology requires angiography. However, proof of coexisting deep venous thrombosis is an alternative way to enhance the diagnosis in case of poor clinical conditions or other practical considerations.

Angiography, Digital Subtraction↗
PubMed1990

[Pneumopathy caused by methotrexate].

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.

Adult↗
PubMed1990

Pharmacokinetics of amiodarone in the isolated rat lung.

In these studies we examined the kinetics of amiodarone (Am) uptake and efflux in/from the lung, and the influence of other amphiphilics on these processes. We used single-pass perfused isolated lungs from rats. Medium containing Am (30 microM + 1 microCi of [14C]Am) was perfused through the lung for 20 min (uptake), followed by 20 min of perfusion with drug-free medium (efflux). Lack of metabolism enabled us to follow Am by measuring the amount of radioactivity in perfusate and lung. Other concentrations of Am (3, 60 and 120 microM; n = 2-4 each) were also examined. Inhibited uptake and accelerated efflux of Am were attempted with the pneumophilic amphiphilics chlorimipramine, chlorphentermine, chlorpromazine, verapamil and with the main metabolite of Am: desethylamiodarone (60 and/or 240 microM; n = 3-4 lungs each). Lung extracted Am extensively during uptake. The amount of Am accumulated at 20 min (inflowing concentration: 30 microM) averaged 1307 +/- 109 (S.E.) nmol/g, corresponding to a tissue to medium ratio of 43.3 +/- 1.6. Spontaneous efflux of Am was incomplete. At 40 min, 862 +/- 105 nmol of Am remained bound per g of lung, suggesting sequestration of Am in a slowly effluxable pool in which calculations show that more than 50% of the drug will ultimately persist. Uptake and efflux rates obey biexponential kinetics, indicating storage into two pools. Uptake rate and the amount of Am accumulated in lung at 20 min increased in proportion to inflowing concentration up to 60 microM. At 120 microM the increase was less. Neither amphiphilic was capable of inhibiting Am uptake, whereas only chlorphentermine significantly accelerated Am efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1988

Types of interaction of amphiphilic drugs with phospholipid vesicles.

Binding characteristics of nine amphiphilic drugs, which induce pulmonary phospholipidosis, to L-alpha-dipalmitoyl phosphatidylcholine (DPPC) vesicles were studied using fluorescence probes, 1,6-diphenyl-1,3,5-hexatriene and 1-anilino-8-naphthalene sulfonate (ANS) for hydrophobic and hydrophilic interactions, respectively. Drug binding to DPPC was quantitated using Scatchard analysis. The tested drugs bound to DPPC with different capacities. The order of binding capacity to hydrophobic site of DPPC using 1,6-diphenyl-1,3,5-hexatriene as fluorescence probe was promethazine greater than amiodarone greater than chlorpromazine greater than chloramphenicol greater than imipramine greater than trimipramine greater than propranolol much greater than chloroquine and chlorphentermine. Two binding affinities were evident for amiodarone, chlorpromazine, imipramine, trimipramine and promethazine. The order of binding strength at high affinity site was amiodarone greater than trimipramine greater than chlorpromazine greater than promethazine greater than imipramine. The order of drug binding capacity using ANS as fluorescence probe was chlorphentermine greater than trimipramine greater than propranolol much greater than amiodarone, chloroquine and chloramphenicol. Each of these drugs displayed a single binding affinity. Imipramine and chlorpromazine at 1 mM and higher concentrations showed intense fluorescence with ANS (5-20 microM) in the absence of DPPC indicating an interaction of these drugs with ANS. Chloroquine did not bind to either sites on DPPC. The binding of these drugs and their interactions with hydrophobic or hydrophilic sites of DPPC were correlated with their capacity to induce pulmonary phospholipidosis. These results indicate that not all the drugs which bind to DPPC in vitro induce phospholipidosis in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1987

Amiodarone is more efficient than verapamil in reversing resistance to anthracyclines in tumour cells.

We have previously demonstrated that amiodarone is able to reverse resistance of rat colon cancer cells to anthracyclines. We now compare the efficiency of amiodarone to verapamil one, another antiarrhythmic agent used in experimental systems and in clinical trials to enhance the effects of anthracyclines on resistant cancer cells. Amiodarone is more efficient than verapamil when both drugs are used at the same molar concentrations. Desethylamiodarone, the main metabolite of amiodarone, is as efficient as its precursor. Optimal concentrations of amiodarone are obtained without side effects in the sera of patients treated by oral administration followed by a loading infusion of amiodarone. On the other hand, maximal tolerated levels of verapamil reported in clinical trials are less efficient than amiodarone maximal levels in the reversal of resistance to anthracyclines in our experimental model in vitro. We suggest that amiodarone, which is more efficient and less toxic than verapamil, could be substituted for verapamil in future clinical trials.

Adenocarcinoma↗
PubMed1987

[Tricuspid endocarditis with right-left auricular shunt through a patent foramen ovale].

The authors report the case of a tricuspid endocarditis secondary to Streptococcus bovis with important regurgitation and severe hypoxemia secondary to a right-left atrial shunt through a patent foramen ovale, requiring a surgical treatment which included the replacement of the tricuspid valve and closure of the dehiscence in the inter-atrial septum. The presence of a patent foramen ovale in the course of a tricuspid endocarditis has been exceptionally reported. This diagnosis deserves to be evoked in case of an unexplained hypoxic condition or a systemic embolism complicating a tricuspid endocarditis. The report emphasizes the advantage of ultrasonic examinations (contrast sonocardiography, pulsated Doppler) in order to demonstrate this right-left atrial shunt in addition to the data collected about the tricuspid valve.

Adult↗
PubMed1986

[Congenital paravertebral arteriovenous fistulae in children and adolescents].

These arteriovenous fistulae (AVF) situated in the paravertebral area present as a murmur which explains their cardiological orientation. They are characterised by the presence of one or more afferent paravertebral arteries giving rise to collateral vessels irrigating the bone marrow. The aim of this study of 13 cases was to study the diagnostic and therapeutic problems, and the evolution of this particular localisation of AVF. Two groups of paravertebral AVF were individualised: - Cervical AVF in which the vertebral artery was always involved (7 cases). Four were simple (only one fistula) and three were complex, having several afferent arteries. Two presented as a rapidly growing vascular tumour. Two caused an asymptomatic angiographic vertebral steal syndrome. Two simple forms were obturated by a detachable balloon and one by surgical excision. Two complex forms were treated by embolisation and surgery. Total closure of the AVF was obtained in all cases without complications. - Dorso-lumbar AVF (6 cases). The afferent vessels are the intercostal (D6 to D8) or lumbar (L2 to L4) arteries. Anatomically, these are extra-medullary fistulae with an extra or intra-vertebral venous drainage. Enlargement in an adjacent conjugating foramen forms a tumour which may narrow the spinal canal (1 case diagnosed by CAT) or erode the vertebral body, so compromising the spinal support. Spontaneous closure of the AVF was observed in 1 case. Three cases were treated surgically with good results; two patients are waiting for embolisation. A review of the literature provides complementary information on the long-term evolution of these AVF and confirms the need for systematic therapy as demonstrated in our study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗