[Proper use of apixaban: an outline for clinical practice]. / Bon usage d'apixaban: que retenir pour la pratique.

Apixaban is a direct inhibitor of coagulation factor Xa. Superior efficacy over aspirin and antivitamin K has been shown in the prevention of stroke and systemic embolism during non-valvular atrial fibrillation with a more favorable safety profile, even though the risk of hemorrhage cannot be ignored, considering its mechanism of action. The recommended dose is 5mg twice daily which can be reduced to 2.5mg depending on the individual risk. Apixaban is also indicated for the treatment of venous thromboembolism but reimbursement has not yet been accepted in France for this indication. As with all direct oral anticoagulants, no routine biological monitoring is required, nevertheless their use may have an impact on all coagulation tests, eventually hampering interpretation. In particular clinical circumstances where a measure of anticoagulant efficacy is deemed necessary, specific assay of anti-Xa activity is appropriate, the result being expressed as concentration of the anticoagulant used. It is therefore necessary to state the name of the medicine for which the assay is requested. With these new anticoagulants, management of hemorrhagic events can be more difficult due to the lack of a specific antidote. Pro-hemostatic substances have exhibited efficacy in animal models but results are still insufficiently documented in clinical practice. Local or locoregional hemostasis measurements, when possible, are an essential factor in the treatment of hemorrhagic events.

Extra-corporeal liver BNCT for the treatment of diffuse metastases: what was learned and what is still to be learned.

Almost eight years ago, in December 2001, we performed for the first time in the world thermal neutron irradiation on an isolated liver of a patient. The organ was affected by diffuse metastases of a colon carcinoma and had been previously loaded with a (10)B compound. In July 2003, the same procedure was applied again on a patient for the treatment of unresectable and incurable hepatic metastases of a carcinoma of the rectum. Both patients are dead at present. Now we can analyze in depth the clinical history of these patients and evaluate the effectiveness of this therapy. From this exciting experience we learned much, and we also found out about complications till then unknown, which need to be studied and addressed experimentally. Unfortunately we can base our conclusions just on the experience we had with these two patients. We could have been much more detailed and firm in our statements if the number of clinical cases was larger. The BNCT Pavia project has been suspended, but it is more than likely to resume in a short time. Good findings were many. The procedure is feasible; the original concept of complete immersion of the diseased liver in a homogeneous neutron field proved effective and winning. The tumor masses resulted completely necrotic and unknown metastases too appeared radically treated; healthy hepatic tissue was preserved from both morphological and functional points of view; no symptoms of cirrhosis appeared even four years after treatment. For the long term surviving patient, quality of life was excellent. Other findings require to be tackled in depth. The "post-irradiation syndrome" we observed in both patients, with identical symptoms and biochemical derangements, creates a dramatic--even though totally reversible--clinical condition, that is the probable cause of death for our second patient, suffering from cardiomyopathy, 33 days after treatment. For the first patient, recurrences were a late yet fatal complication, for which even a further surgical revision was ineffective. We offer some hypotheses about their origin and possible prevention.

Neutron autoradiography imaging of selective boron uptake in human metastatic tumours.

The ability to selectively hit the tumour cells is an essential characteristic of an anti-tumour therapy. In boron neutron capture therapy (BNCT) this characteristic is based on the selective uptake of (10)B in the tumour cells with respect to normal tissues. An important step in the BNCT planning is the measurement of the boron concentration in the tissue samples, both tumour and healthy. When the tumour is spread through the healthy tissue, as in the case of metastases, the knowledge of the different kinds of tissues in the sample being analysed is crucial. If the percentage of tumour and normal tissues cannot be evaluated, the obtained concentration is a mean value depending on the composition of the different samples being measured. In this case an imaging method that could give information both on the morphology and on the spatial distribution of boron concentration in the sample would be a fundamental support. In this paper, the results of the boron uptake analysis in the tumour and in the healthy samples taken from human livers after boron phenylalanine (BPA) infusion are shown; boron imaging was performed using neutron autoradiography.

[Pulmonary alveolar proteinosis: report of two cases and review of the literature]. / Proteinosis alveolar pulmonar: presentación de dos casos y revisión de la bibliografía.

Pulmonary alveolar proteinosis is a rare disease characterized by extensive radiological and tomographic pulmonary lesions and a variable clinical picture ranging from pulmonary insufficiency to spontaneous remission. Among its three described forms, the so called Idiopathic or Adult form is responsible for more than 80% of published cases. It's physiopathology depends on an autoimmune process directed against the GM-CSF (Granulocite Macrophage- Colony Stimulating Factor) that induces a functional defect of the macrophage with consequent intraalveolar accumulation of surfactant. Pulmonary and extrapulmonary infections, are common, often with unusual pathogens. Diagnosis can be made from the combination of clinical, radiological and bronchoalveolar lavage data, although sometimes histopathologic material is needed for confirmation. Total pulmonary lavage is currently the treatment of choice. Mortality is usually low and related mostly to infectious complications. We hereby describe our experience with two patients.

How to study boron biodistribution in liver metastases from colorectal cancer.

The purpose of this study was to evaluate boron distribution for a safe and effective BNCT (Boron Neutron Capture Therapy) of liver metastases. Samples both from healthy and tumour liver parenchyma were analysed, after i.v. boron administration, by: alpha particles counting under neutron irradiation; morphological analysis by standard haematoxylin-eosin staining; neutron autoradiography. Our method was unaffected by the cytological heterogeneity inside tumour nodules; it demonstrated selective boron distribution in tumour tissue and predicted estimated mean therapeutic doses in tumour and safety doses in healthy tissue. The time interval for efficient BNCT was 2 to 4 hours after i.v. boron administration.

Serum and cerebrospinal fluid human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) in intracranial germ cell tumors.

We report a retrospective study on serum and cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (betahCG) determination in a series of 30 patients bearing intracranial germ cell tumors. At diagnosis five patients had high serum and CSF AFP levels. No patient had positive serum AFP and negative CSF AFP or vice versa. Twelve of 30 patients had serum betahCG levels above 5 mlU/mL, eight had high betahCG only in CSF, and ten were completely negative. During treatment and follow-up both markers were accurate indicators of the response to therapy, decreasing rapidly and often becoming normal already after the first phase of treatment. We conclude that these two markers, and mostly betahCG, may be useful in the diagnosis and monitoring of the response to therapy of patients with intracranial germ cell tumors.

[Ablation of the slow pathway in reciprocating nodal rhythms by radiofrequency]. / Ablation de la voie lente des rythmes réciproques nodaux par application d'un courant de radiofréquence.

Radiofrequency ablation is a therapeutic alternative to drug therapy in recurrent reciprocating nodal rhythms. Selective ablation of the slow pathway guided by endocavitary recordings has the advantage of being effective at the price of a very low incidence of atrioventricular block. The authors report their experience with this technique. Fifty consecutive patients with recurrent attacks which were syncopal or uncontrolled by medical therapy, underwent selective ablation of the slow pathway. Firstly, they all underwent electrophysiological investigation to confirm the nodal origin of the reciprocating rhythm before proceeding to ablation itself, guided by the search for the slow pathway potentials. After ablation, it was impossible to trigger reciprocating tachycardia. Interruption of the anterograde slow pathway was achieved in 24 patients and of the retrograde pathway in 1 patient : the other 25 patients went on having dual conduction but with a prolongation of the effective refractory period of the slow pathway (268 +/- 46 ms vs 251 +/- 41 ms : p < 0.01). There were no cases of permanent complete atrioventricular block. Interruption of the slow pathway was associated with shortening of the effective refractory period of the rapid pathway (323 +/- 71 ms vs 348 +/- 80 ms : p < 0.01), which was not observed in cases of persistent dual conduction. No recurrence of tachycardia was observed during follow-up (mean period = 19.2 months) : however, control endocavitary studies in 25 asymptomatic patients after 1 to 3 months showed recurrence in 4 cases, which led to immediate further radiofrequency ablation which was successful. The authors conclude that guided selective radiofrequency of the slow intranodal pathway is a remarkably effective and reliable method of treating poorly tolerated or resistant reciprocating nodal tachycardias. Widening of the clinical indications to patients not wishing to undergo long-term antiarrhythmic therapy is now possible.

A soap technique for cell separation to study the seed coat of Sesbania punicea.

A technique is described for separating plant cells used for morphological studies. The plant material is placed in a concentrated solution of olive oil castile soap for 1-2 days or more. The material is then thoroughly washed and placed between two glass slides. The upper glass slide is lifted from the lower one, then gently pressed down several times. Through this procedure Malpighian cells of the seed coat of Sesbania punicea, mesophyll cells of Euphorbia peplus and of Trifolium pratense and cortical cells of the aerial roots of Monstera deliciosa have been separated. Various shapes of the Malpighian cells of the Sesbania punicea seed coat can be observed along with intermediates.

[Contribution of transesophageal echocardiography in the diagnosis of intra- and para-cardiac masses]. / Apport de l'échocardiographie transoesophagienne dans le diagnostic des masses intra- et paracardiaques.

The authors detected 59 thrombi and 7 intra- or paracardiac tumors in 58 patients in a series of 1,100 transesophageal echocardiography. Twenty-six of the 51 patients with a thrombus were in sinus rhythm; 25 had atrial fibrillation. In 44 cases, the thrombus was single and in 7 cases there were multiple thrombi. A phenomenon of spontaneous contrast in the left atrium was observed in 24 patients (47%). In 31 cases (53%) the thrombi were located in the left auricle, in 21 cases (36%) in the left atrium, in 4 cases in the left ventricle and in 3 cases in the right atrium. Transthoracic echocardiography only detected 25% of these thrombi. The superiority of transesophageal echocardiography was particularly evident for the detection of thrombi in the left auricle (31 by transesophageal echocardiography versus 2 by transthoracic echocardiography) and in the left atrium (13 by transesophageal echocardiography versus 7 by transthoracic echocardiography). Five myxomas were diagnosed by transesophageal echocardiography and 4 of them were identified by transthoracic echocardiography. The site of implantation of the tumor was located in all 5 cases by transesophageal echocardiography. Two right paracardiac tumours were only visible by transesophageal echocardiography. Transesophageal echocardiography is therefore very useful in the diagnosis of thrombi in the left atrium and auricle, of rare hypodense myxomas and paracardiac tumors. In addition, it enables precise localisation of the site of implantation of nearly all intracardiac tumors.

[Cerebral arteriovenous malformations (CAVM)]. / Le malformazioni artero-venose endocerebrali (MAV).

Two infants with endocranic A-V malformations and irreversible picture of congestive cardiac failure are presented: the first is a newborn with a very large angioma, the second is a newborn with a large aneurysm of the vein of Galen. A review of the literature is presented: the salient age-related features required to make a diagnosis are discussed.

Determination of vinyl chloride monomer residue in poly(vinyl chloride) at the parts-per-billion level with an automatic purge-and-trap technique.

A method for the determination of vinyl chloride residue in poly(vinyl chloride) using a commercial purge-and-trap ancillary unit has been developed. Concentrations lower than 10 ppb (10(9] with relative standard deviations in the region of 10% in up to 24 samples are detectable with fully automatic operation without operator attendance. With multiple extraction of the same sample an external standard is used; the matrix does not have any influence on the recovery of vinyl chloride.

Laboratory tests of three repellents against Phlebotomus perniciosus (Diptera:Psychodidae).

Three topical repellents were evaluated against Phlebotomus perniciosus using dose-response techniques. A total of 1800 laboratory reared nulliparous females of P. perniciosus, 2 to 15 days old, and 21 human volunteers were used. The effective dose (ED50 and ED90) for Deet, Indalone and MGK 11 has been determined. Indalone and MGK 11 were more effective than standard Deet. The data obtained indicate that P. perniciosus is highly sensitive to the repellents compared with other blood-sucking arthropods.