Comparative study and clinical implementation of two breathing-adapted radiotherapy techniques: dosimetric benefits for lung cancer treatment]

Breathing can lead to organ motions up to several centimeters. For radiotherapy of lung, these motions are generally taken into account by adding a specific margin around the target. Thus, treated volumes are often too large to allow for the high-dose values requested for local control. To manage respiratory motion, deep-inspiration breath-hold technique (DIBH) and gated radiotherapy are starting being used clinically. DIBH consists in asking the patient to perform breath-hold during the treatment and the image acquisition, DIBH level being measured by a spirometer. Gated radiotherapy consists in treating the patient at a certain phase of the free breathing. Linac is synchronized with the motion of a marker located on the patient chest. Planning images are obtained by a four-dimensional CT (4D-CT) using the same marker. We have assessed the value of these two methods. For lung treatment, compared to a standard treatment, toxicity reduction was mainly due to the lung total volume increase. It is therefore more significant for breath-hold approach. It is also due to the reduction of safety margins, which is similar for both methods. These two techniques, which have specific advantages and drawbacks, are used routinely at Curie Institute for a large proportion of lung patients, but also for some breast, liver or even Hodgkin disease treatments.     

Isolated right ventricular dysfunction in systemic sclerosis: latent pulmonary hypertension?

Right ventricular function is frequently abnormal in patients with systemic sclerosis, but whether this is related to pulmonary vascular complications of the disease is unclear. Standard echocardiography with tissue Doppler imaging was performed at rest and during exercise for the study of right ventricular function and pulmonary circulation in 25 consecutive systemic sclerosis patients and in 13 age-matched healthy controls. When compared with the controls, the patients had no difference in systolic right ventricular pressure gradient, but a decreased pulmonary flow acceleration time, and increased right ventricular free wall thickness and end-diastolic dimensions. At the tricuspid annulus, the E maximal velocity was decreased (8.9 +/- 4 versus 11.7 +/- 2.3 cm.s(-1)) and the isovolumic relaxation time corrected to RR interval was increased (6.5 +/- 2.9 versus 4.5 +/- 2.5%). The tissue Doppler imaging profile at the mitral annulus was similar in both groups. At exercise, 18 patients had a decreased maximum workload and cardiac output, no change in systolic right ventricular pressure gradient, but an increase in the slope of pulmonary artery pressure/flow relationships. These results suggest that patients with systemic sclerosis may present with latent pulmonary hypertension as a likely cause of right ventricular diastolic dysfunction, as revealed by stress echocardiography and tissue Doppler imaging.     

Radiochemical dates obtained by alpha spectrometry on fossil mollusk shell from the 5e Atlantic shoreline of the High Atlas, Morocco.

The reported radiochemical results obtained on 77 samples collected from Moroccan fossil beaches assumed to be deposited during the above present sea-level high stands corresponding to 5e climatic stage, and on 12 present and Holocene samples, are discussed in order to judge the age validity. Contrary to the Holocene shells where (238)U contents are low and (234)U/(238)U are in agreement with sea-water ratio, the 5e results vary considerably irrespective of species and calcite content of samples. Because of the open-system possibility, the (230)Th/(234)U ages based on shell samples should be interpreted as minima for any studied shoreline discussed in the light of geological data and several shells analyses.     

Down-regulation of rat β-adrenoceptors by clenbuterol or desipramine does not require chronic treatment: [H]CGP-12177 binding reveals rapid (24 hour) modulation

Desipramine (DMI, 15 mg/kg, s.c.) decreased [³H]CGP-12177-labelled cortical β-adrenoceptor density (B_max) by 30% upon chronic (14 day) treatment. However, even a single dose (in mg/kg) of DMI (15) or the β-adrenoceptor agonist, clenbuterol (20), induced a rapid (24 hour) and significant reduction of β-adrenoceptor B_max (−15%; p<0.01). Acute treatment with amitryptiline (10), clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no significant effect on [³H]CGP-12177-labelled β-adrenoceptors, suggesting that rapid down-regulation may not be a general property of antidepressant drugs. None of the antidepressants altered the B_max of [³H]ketanserin-labelled 5-HT_2A receptors on acute treatment. These results show that β-adrenoceptor down-regulation by clenbuterol and DMI is not dependent on chronic treatment and may, therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen clinically with antidepressant drugs.     

Intrastriatal infusions of methoctramine improve memory in cognitively impaired aged rats

Alterations of striatal cholinergic markers may correlate with cognitive impairments in aged rats. M2 muscarinic receptors were found to be presynaptic inhibitory autoreceptors on striatal cholinergic interneurons. The effect of bilateral intrastriatal infusions of the M2 muscarinic receptor antagonist methoctramine was assessed, in cognitively impaired aged (24-26 months) Long-Evans female rats, on memory performances in a water maze. Compared with vehicle infusions, methoctramine injected bilaterally (1 microg/side) in the dorsolateral striatum, significantly improved procedural memory performance while having no effect on spatial working memory. Our results suggest that, in cognitively impaired aged rats, the blockade of M2 muscarinic receptors in the dorsolateral striatum improves procedural memory probably by enhancing the release of acetylcholine.     

Small epithelial cells in human liver cirrhosis exhibit features of hepatic stem-like cells: immunohistochemical,electron microscopic and immunoelectron microscopic findings

AIMS: To investigate whether cells with features similar to those of the oval cells of rodents and the small epithelial cells (SEC) recently described in certain human liver diseases, i.e. hepatic progenitor cells, also occur in human liver cirrhosis. METHODS AND RESULTS: Surgical specimens from 35 cases of hepatitis B virus-positive cirrhosis (30 cases containing hepatocellular carcinoma) were investigated by immunohistochemical staining for cytokeratin 7 and albumin. Electron microscopic investigations, and immunoelectron microscopic investigations using the same antibodies and a double-labelling technique were performed in 15 and seven cases, respectively. SEC were observed in proliferated bile ductules, at the margins of regenerating nodules and in the fibrous septa in all cases of cirrhosis. The SEC were morphologically similar to the SEC described previously, and to the oval cells seen in experimental hepatocarcinogenesis. They were characterized by their small size, oval shape, scanty electron-dense or electron-lucent cytoplasm, a high nucleo-cytoplasmic ratio, tonofilaments and intercellular junctions. Immunoelectron microscopy revealed that the SEC co-expressed cytokeratin 7 and albumin. Both relatively undifferentiated SEC and SEC with morphological and immunophenotypical signs of differentiation towards biliary epithelial cells and hepatocytes were found. CONCLUSIONS: SEC that exhibit morphological and immunophenotypical features of the SEC seen in certain other liver diseases are found in cirrhosis. These findings further support the hypothesis that a bipotent hepatic stem cell that may give rise to biliary epithelial cells and hepatocytes exists in the human liver.