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Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.

Interferon (IFN)-alpha with or without ribavirin is the treatment of choice for patients with chronic HCV-related hepatitis. Cough and dyspnea during IFN therapy are often regarded as a side effect and not as a possible sign of the onset of a pulmonary interstitial disease. It may therefore be claimed that the likelihood that patients treated with IFN develop sarcoidosis is being underestimated. Although they are not conventionally classified as etiopathologic agents of sarcoidosis, the IFNs have been proven to be capable of triggering macrophages and of promoting the expression of class II HLA antigens. It is therefore possible that IFN-a treatment could trigger macrophages and promote the polarization of the immune response towards Th1 in the presence of particular susceptibility conditions, thus starting the series of events that lead to the onset of sarcoidosis. We describe a case of pulmonary sarcoidosis in a 33-year-old patient treated with IFN- a2b and ribavirin for chronic HCV-related hepatitis after 6 months of therapy. The case we report here brings forth the issue of a possible underestimation of the real incidence of sarcoidosis during IFN therapy and highlights the need for more attention to and a more careful evaluation of respiratory symptoms manifesting in treated patients.

The aim of our study was to define the changes in morphovolumetric features of neurocranium, basicranium and splanchnocranium in the population of Campania, southern Italy, over the last 2,700 years. This was a very intense period for this region from both historical and evolutionary perspectives and was marked by the succession of colonisations, dominations and invasions by several European and non-European peoples, events that profoundly influenced the original genetic heritage, which subsequently became more complex. Unlike most previous authors, we based our craniometric comparative analysis on multidetector computed tomography (MDCT) studies of contemporary and ancient series dating to between the seventh and fifth centuries B.C. of skulls found in the Etruscan necropolis of Pompei and Pontecagnano. MDCT is extremely reliable in identifying landmarks and measuring linear and angular indices through the use of multiplanar and tridimensional reformations. While highlighting a remarkable stability of 22/32 of the indices considered, as an effect of the role of the genetic heritage in preserving morphovolumetric features in a given population, statistical analysis showed some interesting results: the main changes concerned the splanchnocranium and the occlusion, indicating a higher sensitivity of these districts to environmental factors, mainly related to diet. Conversely, neurobasicranial complex morphovolumetric features remained amazingly intact. In particular, the neurocranium increased in overall capacity in response to the growing brain and changed shape with a progressive shift to a dolichocranic, flattened frontal pattern; the basicranium shape was preserved, as indicated by the stability of the cranial base (NSBa) angle over time. The splanchnocranium, on the contrary, has undergone a dramatic involution, even conditioning gnathic structures with changes in palatal shape (more acute) and in the relationship between the jaws on the sagittal plane, resulting in increased prevalence of Angle's class I and III malocclusions. © 2012 Springer-Verlag Italia. The aim of our study was to define the changes in morphovolumetric features of neurocranium, basicranium and splanchnocranium in the population of Campania, southern Italy, over the last 2,700 years. This was a very intense period for this region from both historical and evolutionary perspectives and was marked by the succession of colonisations, dominations and invasions by several European and non-European peoples, events that profoundly influenced the original genetic heritage, which subsequently became more complex. Unlike most previous authors, we based our craniometric comparative analysis on multidetector computed tomography (MDCT) studies of contemporary and ancient series dating to between the seventh and fifth centuries B.C. of skulls found in the Etruscan necropolis of Pompei and Pontecagnano. MDCT is extremely reliable in identifying landmarks and measuring linear and angular indices through the use of multiplanar and tridimensional reformations. While highlighting a remarkable stability of 22/32 of the indices considered, as an effect of the role of the genetic heritage in preserving morphovolumetric features in a given population, statistical analysis showed some interesting results: the main changes concerned the splanchnocranium and the occlusion, indicating a higher sensitivity of these districts to environmental factors, mainly related to diet. Conversely, neurobasicranial complex morphovolumetric features remained amazingly intact. In particular, the neurocranium increased in overall capacity in response to the growing brain and changed shape with a progressive shift to a dolichocranic, flattened frontal pattern; the basicranium shape was preserved, as indicated by the stability of the cranial base (NSBa) angle over time. The splanchnocranium, on the contrary, has undergone a dramatic involution, even conditioning gnathic structures with changes in palatal shape (more acute) and in the relationship between the jaws on the sagittal plane, resulting in increased prevalence of Angle's class I and III malocclusions.

Orthodeoxia-platypnea is a rare but increasingly recognized syndrome of upright hypoxemia usually associated to breathlessness relieved by recumbency. We report the case of isolated orthodeoxia discovered in a military recruit who referred only fatigability as the clinical symptom after a forced march. Transesophageal echocardiography demonstrated the presence of interatrial defect ostium secundum type with the persistence of left superior vena cava draining into coronary sinus. Right-to-left shunt was visualized by peripheral saline contrast infusion, despite normal right hemodynamics at heart catheterization. Hypoxemia recovered after the percutaneous closure of the interatrial defect. Orthodeoxia and platypnea could occur as separate disease manifestations, the latter probably being a rarer acute event, whereas orthodeoxia was underestimated and potentially earlier screenable.