Isabelle Leconte

Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension.

OBJECTIVES The purpose of this study was to investigate the effects of bosentan (125 or 250 mg twice daily) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension (PAH). BACKGROUND Bosentan, an orally active dual endothelin-receptor antagonist, improves symptoms, exercise capacity, and hemodynamics in patients with PAH. METHODS Patients had primary pulmonary hypertension (84%) or PAH associated with connective tissue disease. Of these, 29 patients received placebo and 56 received bosentan (1:2 randomization). Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment. RESULTS Baseline characteristics were similar in the placebo and bosentan groups, and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular (RV) and left ventricular (LV) structure and function that were due to PAH. The treatment effect on 6-min walking distance was 37 m in favor of bosentan (p = 0.036). Treatment effects of bosentan compared with placebo on other parameters were as follows: Doppler-derived cardiac index = +0.4 l/min/m(2) (p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm(2) (p = 0.003), LV systolic eccentricity index = -0.12 (p = 0.047), RV end-systolic area = -2.3 cm(2) (p = 0.057), RV:LV diastolic areas ratio = -0.64 (p = 0.007), Doppler RV index = -0.06 (p = 0.03), and percentage of patients with an improvement in pericardial effusion score = 17% (p = 0.05). CONCLUSIONS Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.

Focal nodular hyperplasia: natural course observed with CT and MRI.

PURPOSE The purpose of this work was to assess the natural course of biopsy-proven focal nodular hyperplasia (FNH). METHOD Eighteen biopsy-proven FNHs in 14 patients (12 women and 2 men) who were followed for at least 6 months with CT and/or MRI were included in the study. The volume of the lesions was calculated twice by two observers using the summation of areas method. Intra- and interobserver variability was assessed by intraclass correlation coefficients. Longitudinal data analysis was performed with generalized estimating equations. RESULTS The volume of FNH was stable in 6 cases, decreased in 10 cases, and increased in 2 cases. Intra- and interobserver variability in size measurements was 5-10%. Intraclass correlation coefficients were >0.992. Longitudinal data analysis showed that there was a general trend of lesion regression. CONCLUSION Long-term follow-up and objective measurements performed in patients with biopsy-proven lesions show that the natural course of FNH is variable. In particular, lesion regression is not rare.

Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1)

No therapy is known to improve health-related quality of life (HRQoL) or dyspnoea in patients with idiopathic pulmonary fibrosis. The present study investigated longitudinal changes in HRQoL and dyspnoea and explored the effects of bosentan on these end-points during the Bosentan Use in Interstitial Lung Disease (BUILD)-1 trial. In total, 154 subjects received oral bosentan (n = 71) or placebo (n = 83). Changes in HRQoL and dyspnoea from baseline to month (M) 6 and up to M12 were measured using the St George’s Respiratory Questionnaire (SGRQ), 36-item short-form health survey (SF-36), Transition Dyspnoea Index and Borg dyspnoea index. Overall, minimal changes occurred in measures of HRQoL and dyspnoea among placebo-treated subjects during the study. The effects of bosentan treatment on HRQoL and dyspnoea in the all-treated population were minimal. However, in the subset of subjects who had undergone surgical lung biopsy for diagnosis of idiopathic pulmonary fibrosis, treatment effects were observed up to M12 in the impact domain of the SGRQ and the physical functioning, general health and role emotional domains of the SF-36. HRQoL and dyspnoea changed minimally during the course of the present study. Observations from exploratory analyses suggested benefits of bosentan on HRQoL among patients who had undergone surgical lung biopsy for diagnosis, and they merit further investigation.

Mechanisms of action of liver contrast agents: impact for clinical use.

New contrast agents for magnetic resonance imaging are continually being developed by pharmaceutical companies in order to better image the liver. These agents can be divided into hepatobiliary agents directed to the hepatocytes and nanoparticulate agents directed to the reticulo-endothelial system. After intravenous injection, all these agents concentrate in the liver and induce profound changes in signal intensity. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a brief description of the principal characteristics of the agents, this paper will attempt to summarize the utility of these agents for the detection and characterization of focal liver disease.

MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD)-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7), Fas death receptor ligand, osteopontin and procollagen type I C-peptide), to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression. MMP-7 is a predictive biomarker in IPF http://ow.ly/c69Y309aO4R

Spontaneous metritis related to the presence of vaginal septum in pregnant Sprague Dawley Crl:CD(SD) rats: impact on reproductive toxicity studies

Recently, 6% of 1,176 Sprague Dawley rats examined in our reproductive toxicity studies presented with dark-red uterine contents with or without fetuses demonstrating delayed development. Sometimes, a high proportion of the litter was found dead, and dystocia with death or preterminal euthanasia of the dam occurred. Microscopic findings in the uterus consisted of necrohemorrhagic and suppurative periplacentitis associated with the presence of bacterial colonies identified as Escherichia coli. In the vagina, similar findings were observed that were associated with mucus accumulation and the presence of a transverse occlusive or partially occlusive thin membrane identified as a vaginal septum. Microscopically, this septum consisted of a thin band of connective tissue covered on both sides by a mucous epithelium that was continuous with vaginal epithelium. In some cases, there was only mucus accumulation retained by a septum in the vagina without evidence of bacterial infection. Serological and histological examinations did not reveal any specific pathogenic agent. The presence of these septa in the vagina most likely favored mucus accumulation, nonspecific ascending bacterial infection, and dystocia. This colony of rats presented with an unusually high incidence of vaginal septa as it was described in different strains of mice and rats in the past. We hypothesized that the use of an impedance meter by the breeder—to determine the phase of the estrous cycle by introducing a probe in the vagina—likely facilitated gestation by perforating the vaginal septum in some cases.

MRI of iron-oxide labelled transplanted hepatocytes in mice : effect of treatment with cyclophosphamide

To assess if 1.5T MRI can be used to study the transport to the liver, the intrahepatic distribution and engraftment of iron‐oxide labelled hepatocytes in cyclophosphamide‐treated and untreated mice.

Échographie et seins denses : où en est-on ?

The use of ultrasonography in dense breast remains a controversial topic. It is acknowledged that ultrasound as an adjunct to mammography increases the detection rate of breast cancers. However, the main limitation of US, in addition to its operator dependent nature, is its low specificity, leading to a high rate of false positive results. Several techniques can be used to improve the performance of US and cost/effectiveness ratio, such as Doppler imaging, harmonic imaging, spatial and frequency compound imaging, all of which are routinely available, and elastosonography, contrast US and 3D US which are still in development.

Papillomatose juvénile mammaire

The authors report a patient with juvenile papillomatosis of the breast presenting with a palpable mass and illustrate the correlation between mammographic, sonographic and pathologic features.

Fibroadenoma: can fine needle aspiration biopsy avoid short term follow-up?

OBJECTIVE To confirm whether fine needle aspiration biopsy (FNAB) can avoid close monitoring, a source of worry for women patients with a suspected fibroadenoma found by ultrasound, and requiring their compliance. PATIENTS AND METHODS Over 39months, 427 nodules with a diagnosis of fibroadenoma were sampled in 372 patients using ultrasound-guided FNAB. The sonographic appearance of all the nodules suggested BI-RADS category 3 fibroadenomas. The mean size of the fibroadenomas was 9mm. The mean duration of follow-up was 29.7months. RESULTS Seven nodules had atypical cytology: a microbiopsy and/or excision found a simple fibroadenoma (n=3), mastitis (n=1), a fibroadenoma associated with a papilloma (n=1), fibrosis (n=1) and normal tissue (n=1). Seven other nodules were resected during treatment for synchronous cancer, and were diagnosed as fibroadenomas. Two hundred and seventy-six nodules were followed-up (121 patients were lost to follow-up [n=132]) and the appearance of 263 nodules (95.29%) was stable. Seven nodules, which had increased in size, underwent another FNAB or microbiopsy or surgery. Five nodules were not found again. The borders of one nodule showed modifications. CONCLUSION The use of fine needle aspiration biopsy, interpreted by an experienced cytologist, means that short term follow-up of fibroadenomas can be avoided.