The predictive value of ABCB1, ABCG2, CYP3A4/5 and CYP2D6 polymorphisms for risperidone and aripiprazole plasma concentrations and the occurrence of adverse drug reactions.

We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c.421 non-CA/AA genotypes (P-value: 0.008). Multivariate analysis revealed that the ABCG2 c.421 CA/AA genotype was found associated to a higher hazard (P-value: 0.004) of developing adverse drug reactions classified as metabolism and nutrition disorders. The ABCB1 2677TT/3435TT genotype had a statistically significant lower aripiprazole Ct/ds if compared with patients with others ABCB1 genotypes (P-value: 0.026). Information obtained on ABCB1 and ABCG2 gene variants may result useful to tailor treatments with these drugs in Caucasian pediatric patients.

Quetiapine-Induced Hypomania and its Association with Quetiapine/Norquetiapine Plasma Concentrations: A Case Series of Bipolar Type 2 Patients.

International guidelines consider quetiapine at medium doses (300-400 mg/day) as valid options for the treatment of bipolar depression for the supposed lower risk of a switch to hypomania/mania than antidepressants. Norquetiapine is an active metabolite with antidepressant action. We describe three cases of induced hypomania in bipolar type 2 subjects who received quetiapine extended-release monotherapy (300 mg/day) for a mild/moderate major depressive episode. Quetiapine and norquetiapine plasma concentrations were measured after 1 week of treatment. Hypomania appeared after 7-10 days of quetiapine extended-release monotherapy and all subjects had a quetiapine/norquetiapine plasma concentration ratio <1. We propose a ratio value <1 as a predictor of risk for a switch to hypomania in bipolar depressed subjects receiving quetiapine extended-release monotherapy. Future research should ascertain the validity of this laboratory parameter to assess the risk of quetiapine-induced hypomania in large samples of bipolar patients.

PGC-1α buffers ROS-mediated removal of mitochondria during myogenesis.

Mitochondrial biogenesis and mitophagy are recognized as critical processes underlying mitochondrial homeostasis. However, the molecular pathway(s) coordinating the balance between these cellular programs is still poorly investigated. Here, we show an induction of the nuclear and mitochondrial peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) during myogenesis, which in turn co-activates the transcription of nuclear and mtDNA-encoded mitochondrial genes. We demonstrate that PGC-1α also buffers oxidative stress occurring during differentiation by promoting the expression of antioxidant enzymes. Indeed, by downregulating PGC-1α, we observed an impairment of antioxidants expression, which was accompanied by a significant reactive oxygen species (ROS) burst and increase of oxidative damage to proteins. In parallel, we detected a decrease of mitochondrial mass and function as well as increased mitophagy through the ROS/FOXO1 pathway. Upon PGC-1α downregulation, we found ROS-dependent nuclear translocation of FOXO1 and transcription of its downstream targets including mitophagic genes such as LC3 and PINK1. Such events were significantly reverted after treatment with the antioxidant Trolox, suggesting that PGC-1α assures mitochondrial integrity by indirectly buffering ROS. Finally, the lack of PGC-1α gave rise to a decrease in MYOG and a strong induction of atrophy-related ubiquitin ligases FBXO32 (FBXO32), indicative of a degenerative process. Overall, our results reveal that in myotubes, PGC-1α takes center place in mitochondrial homeostasis during differentiation because of its ability to avoid ROS-mediated removal of mitochondria.

Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation.

The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-α, peroxisome proliferator-activated receptor-γ coactivator-1α), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders.

Extranuclear localization of SIRT1 and PGC-1α: an insight into possible roles in diseases associated with mitochondrial dysfunction.

SIRT1 and PGC-1α are two nutrient sensing master regulators of cellular metabolism and their upregulation is often linked to increased lifespan. SIRT1 and PGC-1α modulate the expression of a set of nuclear genes controlling many metabolic pathways. In recent years mounting evidence has indicated the implication of these proteins in several mitochondrial diseases including neurodegenerative disorders, myopathies and Type II diabetes mellitus. Recently, these proteins have been localized in cytoplasm and mitochondria wherein they target novel substrates opening new insight into their possible function in modulating extranuclear genes and proteins. This review will firstly summarize the nuclear function of SIRT1 and PGC-1α. Then, data from papers demonstrating the presence of SIRT1 and PGC-1α in the cytoplasm and in mitochondria will be outlined so that these extranuclear forms do not remain out of sight. Finally, very recent evidence of the alteration of the pathways governed by SIRT1 and PGC-1α in human mitochondrial diseases will be described and the possible role of their mitochondrial forms will be briefly discussed.

[Materno-fetal conflicts and the perinatal Medea syndrome: a cognitive analysis]. / I conflitti materno-fetali e la sindrome di Medea perinatale: un'indagine conoscitiva.

The definition of "maternal-fetal conflict" requires the attribution of a well-defined subjectivity at the product of conception, and thus, from the medical point of view, we need to consider the fetus as a patient. A tangible example of conflict in our society is the "Medea syndrome", a framework in which the female parent kills her fetus or child to take revenge on the partner. We have produced a questionnaire that was administered to 150 women admitted to the Department of "Obstetrics and Gynecology" of the "Santa Maria della Misericordia" Hospital, in Perugia. The results show the importance of the maternal-fetal conflict in our reality through the opinion that women have given in assessing particular situations that we have proposed in the questionnaire.

Pharmacogenetics of immunosuppressants: progress, pitfalls and promises.

Most of the immunosuppressants used in organ transplantation are characterized by a narrow therapeutic index, whereby underdosing is associated with increased risk of rejection episodes and overdosing may exacerbate drug-related toxicity. Pharmacogenetics--complementary to pharmacokinetics--holds the potential to allow individualized dosing of immunosuppressive agents to optimize their therapeutic actions while minimizing adverse effects. Most of the studies have focused on polymorphisms of genes involved in drug metabolism and distribution, but as of now, only thiopurine-S-methyltransferase and cytochrome P 450 3A5 genotypes appear to have sufficiently large influence to have potentialities in guiding drug dosing. This may reflect the fact that available information from other polymorphisms derives almost exclusively from retrospective observations or from studies with important methodological biases. Active investigations aimed at identifying allelic variants of gene encoding for the pharmacologic targets are now ongoing. Recent studies have demonstrated that also donor genotype may play a significant role in immunosuppressive drug pharmacokinetics and pharmacodynamics. As one of the main future tasks, it is mandatory to develop mathematical models able to incorporate multiple gene polymorphisms with pharmacokinetic data and other critical information, providing algorithms able to individualize the best immunosuppressive therapy for each patient before transplantation.

Influence of co-medication with sirolimus or cyclosporine on mycophenolic acid pharmacokinetics in kidney transplantation.

The pharmacokinetics of mycophenolic acid (MPA)--the active metabolite of mycophenolate mofetil (MMF)--is significantly influenced by co-medications. The impact of sirolimus on daily MPA exposure, however, has not been investigated so far. As a part of the study aimed at investigating the efficacy of Campath-1H induction therapy in a steroid-free regimen in kidney transplantation, MPA plasma levels were serially measured in 21 patients treated with low-dose sirolimus (SRL) or low-dose CsA both in addition to low-dose MMF over 12 months post-operatively. Full pharmacokinetic profiles were compared at month 6 and 12 post-surgery. Mean dose-adjusted MPA trough levels were 4.4-fold higher in patients on combined SRL and MMF than in those given CsA and MMF. Pharmacokinetic studies demonstrated that mean MPA C(max) and T(max) were comparable in the two groups, while mean MPA AUC(0-12) was higher in SRL than CsA treated patients. The pharmacokinetic profile of SRL- but not of CsA-group showed a second peak consistent with the enterohepatic recirculation of MPA. These findings suggest that SRL and CsA have different effects on MPA metabolism and/or excretion eventually affecting its immunosuppressive property and/or toxicity. CsA, but not SRL, inhibits MPA enterohepatic recirculation, reducing MPA daily exposure.

Potential-dependent vibrational spectroscopy of solvent molecules at the Pt(111) electrode in a water/acetonitrile mixture studied by sum frequency generation.

Sum frequency generation (SFG) vibrational spectra of D(2)O and/or acetonitrile (CH(3)CN) on a Pt(111) single-crystal electrode were obtained as a function of applied potential in a 5 mol % water/acetonitrile mixed solvent with different 0.1 molar MSO(3)CF(3) salts (M = H(+), Li(+), Na(+), K(+), and Cs(+)). The results provide a very specific model for the composition of the inner Helmholtz layer as a function of potential and surface charge. Acetonitrile dominates the inner layer with the CN group directed toward the metal at potentials where the metal has a positive charge. As the surface becomes negatively charged, the acetonitrile orientation flips 180 degrees, with the CH(3) group pointing toward the surface. At even more negative surface charge, D(2)O displaces acetonitrile from the inner layer and is the predominant molecule on the surface. Here water is present as an oriented molecule with the oxygen end pointing toward the metal. The potential (and surface charge) where water is the dominant molecule in the inner Helmholtz layer is determined by the solvation energy of the cation.

The differing patterns of subclinical pulmonary involvement in connective tissue diseases as shown by application of factor analysis.

To explore common patterns of interstitial lung disease (ILD) in symptomless patients with connective tissue disease (CTD), we applied factorial analysis to determine the relationship among the factors. A selected cohort of 71 non-smoking patients with a confirmed diagnosis of CTD [24 with primary Sjögren's syndrome (pSS), 21 with systemic sclerosis (SS), 20 with rheumatoid arthritis (RA) and six with polymyositis/ dermatomyositis (PM/DM)] were identified. The diagnostic techniques included pulmonary function tests, bronchoalveolar lavage (BAL), chest radiographs and high-resolution computed tomography (HRCT). Disease extent and severity were assessed by a radiological and HRCT grading system. Three factors, accounting for 67% of the total variance, were extracted. The first factor (disease duration, diffusing lung capacity, neutrophils and CD8+ T cells on BAL, radiographic score and HRCT reticular score), with the highest percentage of variance (36.5%), defines a fibrotic lung pattern. The second factor (17.9% of variance) identifies an inflammatory lung pattern (macrophages, lymphocytes and eosinophils on BAL and HRCT ground-glass score). The third factor (12.6% of variance) represents a ventilatory function pattern (forced vital capacity, total lung capacity and forced respiratory volume in 1 s). The negative correlation between the fibrotic lung pattern and ventilatory function pattern, but not with the inflammatory lung pattern, suggests the presence of a significant derangement of the alveolar structures. In conclusion, application of factor analysis reveals various lung disease patterns in patients with CTD that might have different prognostic implications.

[Subclinical interstitial lung involvement in rheumatic diseases. Correlation of high resolution computerized tomography and functional and cytologic findings]. / L'interessamento polmonare interstiziale subclinico nelle malattie reumatiche. Correlazione fra Tomografia computerizzata con alta risoluzione e i reperti funzionali e citologici.

INTRODUCTION: Rheumatic diseases are frequently associated with interstitial lung disease. Since interstitial fibrosis is an irreversible process, understanding the mechanisms leading to fibrosis is necessary for the development of treatment strategies to prevent irreversible pulmonary damage. High-resolution Computed Tomography (HRCT) is superior to chest radiography in assessing the presence and extent of parenchymal abnormalities in diffuse infiltrative lung diseases and provides a sensitive and noninvasive method of quantifying global disease extent. PURPOSE: The aims of this study were to quantify the severity and extent of subclinical interstitial lung disease as depicted on HRCT and to study the relationship between the patterns of lung disease quantified by HRCT and the functional parameters and bronchoalveolar lavage findings in patients with rheumatic diseases. PATIENTS: Eighty nonsmoking patients (24 patients with systemic sclerosis, 24 with primary Sjögren's syndrome, 20 with rheumatoid arthritis and 7 with dermatopolymyositis) were examined. No patient had any signs or symptoms of pulmonary disease. RESULTS: Thirty-three of 80 patients (41.2%) had abnormal HRCT findings, namely isolated septal/subpleural lines, irregular pleural margins and ground-glass appearance. Chest X-ray showed parenchymal abnormalities in only 15 patients (18.7%) who had evidence of fibrosis on HRCT. Abnormal differential cell counts (alveolitis) at bronchoalveolar lavage were found in 46 of 80 patients (57.5%). Three types of alveolitis were observed: pure lymphocyte alveolitis, pure neutrophil alveolitis, and neutrophil alveolitis associated with lymphocytosis (mixed alveolitis). The patients with neutrophil alveolitis had more extensive disease on HRCT than those with lymphocyte alveolitis or with normal cellular patterns at bronchoalveolar lavage. The extent of a reticular pattern on HRCT correlated with the neutrophil rate (p = 0.001) and total count (p = 0.003) on bronchoalveolar lavage. Eosinophil and lymphocyte rate and total count correlated (p < 0.05) with the extent of the ground-glass pattern on HRCT. Lung volumes were not significantly different among patients with ground-glass pattern and those with reticular patterns on HRCT, while the diffusing capacity for carbon monoxide was significantly lower (p < 0.05) in the latter. CONCLUSIONS: HRCT is a sensitive tool in detecting interstitial lung disease in patients with rheumatic diseases with no signs and symptoms of pulmonary involvement. The relationship between the different HRCT patterns and bronchoalveolar lavage cell profiles can identify patients at higher risk of developing irreversible lung fibrosis. A long-term, prospective follow-up study is needed to determine whether these patients will develop over pulmonary disease.

A longitudinal study of pulmonary involvement in primary Sjögren's syndrome: relationship between alveolitis and subsequent lung changes on high-resolution computed tomography.

Eighteen non-smoking women suffering from primary Sjögren's syndrome (pSS) with previously documented alveolitis were re-examined, clinically and by pulmonary function tests (PFT), bronchoalveolar lavage (BAL), chest X-ray and high-resolution computed tomography (HRCT) after a 2 yr follow-up period. Longitudinal evaluation revealed unchanged PFT. The final BAL study showed a normal differential count in six of 14 patients with initial lymphocyte alveolitis, and a persistent alveolar lymphocytosis in the remaining eight patients, associated with an increased percentage of neutrophils in one of them. In four patients with initial mixed alveolitis, the BAL cell profile was unchanged 2 yr later. Five of 18 patients (28%) had abnormal HRCT, represented by isolated septal/subpleural lines in three patients, ground-glass opacities with irregular pleural margins in one patient, and ground-glass opacities associated with septal/subpleural lines in another. All these patients had abnormal BAL results with an increased proportion of both neutrophils and lymphocytes. The presence of alveolar neutrophils was associated with a significantly (P=0.005) greater mean rate of reduction of carbon monoxide diffusing capacity (DLCO) -- more than four times the normal rate of loss of DLCO. Chest X-ray, repeated at the end of the 2 yr follow-up period, showed parenchymal abnormalities in only one patient who had evidence of fibrosis on HRCT. This study provides evidence that lung involvement is not an uncommon extraglandular manifestation of pSS and that a BAL neutrophilia may play an important role in the pathogenesis of pulmonary disease in this autoimmune disorder.

[Quantitative analysis of radiologic progression in rheumatoid arthritis: controversies and perspectives]. / L'analisi quantitativa della progressione radiologica nell'artrite reumatoide: controversie e prospettive.

Rheumatoid arthritis (RA) is a chronic inflammatory disease with symmetrical polyarthritis as the major feature. Persistent inflammation leads to largely irreversible joint damage which can be seen radiographically. Radiographs depict the progression of joint damage and alterations, which are one of the major parameters of RA evolution. Delayed radiologic progression is a good indicator of the success/failure of long-term drug treatment, but the quantitative analysis of changes over time and the reliability of scoring systems remain difficult steps. This paper focuses of the main current scoring systems, with an emphasis on the following four: Larsen method and its modification by Kayle, Sharp method and its modification by van der Heijde. The scoring method--be it grading, counting, or weighted counting--did not appear to influence reliability or repeatability, while the radiologist's training and the film reading technique were critical to identify disease progression accurately. Our data consistently suggest the paired reading method as the most suitable for radiologic progression assessment in RA. The radiologic studies of 62 patients with early RA after 7 years' follow-up showed joint damage in 82% of patients. The average annual progression rate of the total radiologic score obtained with Sharp method, summing erosions and joint space abnormalities, was faster in the earlier years of the disease (8.8 units/year) than later on (4.9 units/year) (p < 0.01). From the trialist's point of view, these results imply that disease duration is a critical feature for RA treatment outcome.

[Virtual bronchoscopy: the correlation between endoscopic simulation and bronchoscopic findings]. / Broncoscopia virtuale: correlazione tra simulazione endoscopica e reperti broncoscopici.

PURPOSE: We carried out a preliminary clinical validation of 3D spiral CT virtual endoscopic reconstructions of the tracheobronchial tree, by comparing virtual bronchoscopic images with actual endoscopic findings. MATERIALS AND METHODS: Twenty-two patients with tracheobronchial disease suspected at preliminary clinical, cytopathological and plain chest film findings were submitted to spiral CT of the chest and bronchoscopy. CT was repeated after endobronchial therapy in 2 cases. Virtual endoscopic shaded-surface-display views of the tracheobronchial tree were reconstructed from reformatted CT data with an Advantage Navigator software. Virtual bronchoscopic images were preliminarily evaluated with a semi-quantitative quality score (excellent/good/fair/poor). The depiction of consecutive airway branches was then considered. Virtual bronchoscopies were finally submitted to double-blind comparison with actual endoscopies. RESULTS: Virtual image quality was considered excellent in 8 cases, good in 14 and fair in 2. Virtual exploration was stopped at the lobar bronchi in one case only; the origin of segmental bronchi was depicted in 23 cases and that of some subsegmental branches in 2 cases. Agreement between actual and virtual bronchoscopic findings was good in all cases but 3 where it was nevertheless considered satisfactory. The yield of clinically useful information differed in 8/24 cases: virtual reconstructions provided more information than bronchoscopy in 5 cases and vice versa in 3. Virtual reconstructions are limited in that the procedure is long and difficult and needing a strictly standardized threshold value not to alter virtual findings. Moreover, the reconstructed surface lacks transparency, there is the partial volume effect and the branches < or = 4 pixels phi and/or meandering ones are difficult to explore. CONCLUSIONS: Our preliminary data are encouraging. Segmental bronchi were depicted in nearly all cases, except for the branches involved by disease. Obstructing lesions could be bypassed in some cases, making an indication for endoscopic laser therapy. Future didactic perspectives and applications to minimally invasive or virtual reality-assisted therapy seem promising, even though actual clinical applications require further studies.

Integration of transbronchial and percutaneous approach in the diagnosis of peripheral pulmonary nodules or masses. Experience with 1,027 consecutive cases.

A study to evaluate the usefulness of the integration of the transbronchial and percutaneous approaches in the diagnosis of peripheral pulmonary nodules or masses (PPN/M) was conducted. The authors used both procedures, performed by a single diagnostic team, a pulmonologist, radiologist, and cytopathologist, who were all simultaneously present in the radiologic suite during the maneuvers. From January 1985 to June 1993, under fluoroscopic guidance, the authors performed 557 transbronchial pulmonary biopsies (TBPB), 483 transbronchial needle aspirations (TBNA), and 652 percutaneous needle aspirations (PCNA) on 1,027 consecutive patients referred because of a PPN/M (mean diameter, 3.5 cm; range, 0.8 to 8 cm). The procedure used was as follows: (1) bronchoscopy with exploration of the upper airways and bronchial tree, followed by TBNA and immediate cytologic assessment (ICA); (2) at least three TBPB; (3) if TBNA was diagnostic, the procedure was stopped; if not, a second pass with the needle was performed and then the bronchoscope was removed; (4) if the second TBNA was not diagnostic, PCNA with ICA was performed up to a maximum of three needle passes. Diagnostic sensitivity for malignant lesions was as follows: 53.9% for TBPB, 69.3% for TBNA, 75.4% for TBPB and TBNA together, 93.2% for PCNA, and 95.2% overall. The percentage of benign nodules correctly defined was 41.4% for TBPB, 17.4% for TBNA, 45.8% for PCNA, and 59.5% overall. Examination of the upper airways and bronchial tree was positive for lesions endoscopically visible in 12.6% of cases. The authors' experience shows that transbronchial and percutaneous approaches must be considered complementary and that their integrated use not only increases diagnostic yield but also permits important information to be obtained for disease staging. The creation of teams able to use both approaches with the cytopathologist present for ICA should be encouraged to optimize the diagnostic management of PPN/M with a reduction in diagnostic and hospitalization time and consequent cost saving.

MR imaging of rheumatoid hand lesions: comparison with conventional radiology in 31 patients.

The purpose of this study was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in rheumatoid arthritis (RA) by comparing MRI with conventional radiology (CR) findings and by correlating these findings with the clinical and serological profile of the disease. The hands of 31 patients (24 females, 7 males) affected by classical RA were studied using a Magnetom 1.0 T tomograph. Coronal, axial, and/or sagittal SE T1 and GE (FLASH 2D FL: 70 degrees-15 degrees) images were obtained in all patients. Moreover, in 7 patients the MRI study was performed after i.v. injection of Gd DTPA contrast medium (0.2 mM/kg). Ten healthy volunteers were also studied as controls. In all patients a conventional radiological study was performed as well as a clinical and serological investigation. Two blinded observers evaluated the MRI and CR findings and checked 15 elementary pathological lesions, assigning an MRI and a CR score to each patient. MRI provided higher accuracy than CR in detecting rheumatoid soft tissue changes and minimal skeletal lesions, while the opposite was true for severe skeletal lesions. No correlations emerged between the MRI/CR findings and clinical and serological data. This study suggests that MRI and CR are complementary techniques in the evaluation of the anatomical changes in RA.

[Magnetic resonance of the rheumatoid hand]. / La risonanza Magnetica nella mano reumatoide.

The purpose of this study was to evaluate MRI diagnostic accuracy in rheumatoid arthritis (RA), to compare MRI and radiological findings and to correlate these findings with the clinical and serological profile of the disease. The hands of 24 patients (20 females, 4 males) affected with typical RA (ARA criteria) were studied using a tomograph Magnetom 1.0 T Siemens. Two patients affected with RA refractory to conventional second-line drugs who received a bolus of methylprednisolone (1 g) were studied before and after such treatment. The hands of healthy volunteers were examined as controls. Besides MRI study all patients underwent: (1) radiological examination of the hands performed with a standard technique and (2) clinical and serological investigation aimed at characterizing diseases activity and extent. The radiographic and MRI findings were evaluated by two different observers who found 15 pathological elementary lesions and assigned a MRI and a radiological score to each patient. MRI exhibited significantly higher accuracy than radiography in evaluating rheumatoid soft-tissue changes and in detecting minimal skeletal lesions, while severe skeletal lesions were better detected by radiology. No correlation was found between pathological MRI findings, radiological results and clinical or serological data. A significant drop in soft-tissue effusion was observed after methylprednisolone pulse in two patients. This study confirms MRI potential in the study of rheumatoid joint lesions and in the early detection of minimal soft-tissue changes. Its use appears to be suitable for accurate monitoring of RA patients under specific therapy.

Lymphangitic carcinomas of the lung as presentation of prostatic cancer. A case report.

Lymphangitic carcinomatosis of the lung is a late and often fatal manifestation of cancer. We describe a case of a biopsy-proved pulmonary lymphangitic carcinomatosis in an asymptomatic 61-year-old man. The pulmonary picture proved to be the initial sign of a prostatic cancer. Therapy with LH-RH analogues and antiandrogens achieved a complete clearance of lung involvement.