Chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension occurs in very few patients who have had history of a previous acute thromboembolic episode. However, its incidence has increased in recent years, actually not being so rare at all. Advances have been made in the pathophysiology, diagnostic approach and therapeutic alternatives as well what can be offered to those patients who are not suitable candidates for pulmonary thromboendarterectomy, which is definitive, curative and the treatment of choice in this subtype of pulmonary arterial hypertension. This review focuses on the diagnostic approach and novel pharmacological therapies in patients who are not candidates for surgery.     

Pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension

Pulmonary arterial hypertension (PAH) secondary to chronic thromboembolic obstruction is a severe and potentially fatal condition. At the same time, PAH represents a real diagnostic challenge. This is a lethal disease in which the natural progression in the majority of cases may not be modified by medical therapy. It may be the only etiology radically cured by a complex surgical procedure being performed successfully at ten medical centers worldwide: the pulmonary thromboendarterectomy. More than three decades after the first successful thromboendarterectomy, improvements in technique in medical centers such as the University of California San Diego, in addition to the achieved advances in cerebral and myocardial protection on the past decades, guarantees at present a low morbimortality rate, offering excellent long-term results, improving quality of life and survival of patients. This review is mainly focused on the historical perspective of pulmonary thromboendarterectomy, indications, patient selection, surgical approach and improvements and outcomes obtained at the most experienced centers worldwide.     

Comparative study on the short term efficacy and adverse effects of miltefosine and meglumine antimoniate in dogs with natural leishmaniosis

The aim of this study was to compare the efficacy and safety of oral administration of miltefosine (Milteforan®) at 2 mg/kg/day for 28 days (Group M; n?=?60) with a subcutaneous administration of meglumine antimoniate (Glucantime®) at 50 mg/kg/12 h or at 100 mg/kg/day for 28 days (Group G; n?=?59) in the treatment of canine leishmaniosis in dogs. Out of 119 dogs included in the study, 90 could be used for efficacy assessment and 112 for safety assessment. Treated dogs were followed up for 6 weeks, with re-checks every 14 days. The mean total clinical scores significantly decreased throughout the study in both treatment groups. The evolution of parasitological results after treatment (D42) shows a high percentage of dogs with negative bone marrow smears, 90% and 91.3% in groups M and G respectively, and did not significantly differ between groups (p?=?0.8066). Out of the 112 dogs used for the safety assessment, only 26 dogs (23.2%) presented product-related adverse events concerning the gastrointestinal tract. These results showed that miltefosine at 2 mg/kg once daily can be safely used over a 28-day period in the treatment of canine leishmaniosis and provides both a steadily increasing improvement of the clinical signs and a good leishmanicidal efficacy.     

Risk of progression in smouldering myeloma and monoclonal gammopathies of unknown significance: comparative analysis of the evolution of monoclonal component and multiparameter flow cytometry of bone marrow plasma cells

The present study explored the impact of two novel criteria; having >95% abnormal plasma cells by flow cytometry at diagnosis and the evolving subtype of the disease, as predictors of progression in 61 smouldering multiple myeloma (SMM) and 311 monoclonal gammopathy of unknown significance (MGUS) patients. Although both criteria were of prognostic value, the risk of progression was better identified by immunophenotyping [Hazard Ratio (HR) 6·2 and 17·2 for SMM and MGUS, respectively] than evolving subtype, which had independent prognostic value only in MGUS (HR 3·6). Immunophenotyping discriminated the different risk of progression within the evolving and non-evolving subgroups of SMM ( P  = 0·01) and MGUS ( P  < 0·001).     

Yellow fever 17-D vaccine is neurotropic and produces encephalitis in immunosuppressed hamsters

Immunosuppressed (cyclophosphamide) adult golden hamsters inoculated intraperitoneally (i.p.) with wild-type Asibi yellow fever virus (YFV) developed a rapidly fatal illness. Histopathologic and immunohistochemical studies of tissues from these animals showed typical hepatic changes of severe yellow fever (inflammation, hepatocyte necrosis, and steatosis) without brain involvement. In contrast, 50% of immunosuppressed hamsters receiving the YFV-17D-attenuated vaccine developed a slowly progressive encephalitic-type illness. Brain tissue from these latter animals revealed focal neuronal changes, inflammation, and YFV antigen-positive neurons; however, the liver and spleen appeared normal. YFV was isolated from brain cultures of many of these animals. Immunocompetent (non-immunosuppressed) hamsters inoculated with both viruses developed a subclinical infection. Results of this study indicate that wild-type YFV is hepatotropic in immunosuppressed hamsters, whereas the attenuated YFV-17 is primarily neurotropic. These findings support current recommendations against yellow fever vaccination of immunosuppressed/immunocompromised people and suggest that this hamster model might be useful for monitoring the safety of other live-attenuated YFV vaccines.     

Dhori virus (Orthomyxoviridae: Thogotovirus) infection in mice: a model of the pathogenesis of severe orthomyxovirus infection

After intranasal, subcutaneous, or intraperitoneal infection with Dhori virus (DHOV), adult mice developed a fulminant and uniformly fatal illness with many of the clinical and pathologic findings seen in mice infected with H5N1 highly pathogenic avian influenza A virus. Histopathologic findings in lungs of DHOV-infected mice consisted of hemorrhage, inflammation, and thickening of the interstitium and the alveolar septa and alveolar edema. Extra-pulmonary findings included hepatocellular necrosis and steatosis, widespread severe fibrinoid necrosis in lymphoid organs, marked lymphocyte loss and karyorrhexis, and neuronal degeneration in brain. Similar systemic histopathologic findings have been reported in the few fatal human H5N1 cases examined at autopsy. Because of the relationship of DHOV to the influenza viruses, its biosafety level 2 status, and its similar pathology in mice, the DHOV-mouse model may offer a low-cost, relatively safe, and realistic animal model for studies on the pathogenesis and management of H5N1 virus infection.     

Anti-ganglioside antibody-induced tumor cell death by loss of membrane integrity

Gangliosides have been involved in multiple cellular processes such as growth, differentiation and adhesion, and more recently as regulators of cell death signaling pathways. Some of these molecules can be considered as tumor-associated antigens, in particular, N-glycolyl sialic acid-containing gangliosides, which are promising candidates for cancer-targeted therapy because of their low expression in normal human tissues. In this study, we provided the molecular and cellular characterization of a novel cell death mechanism induced by the anti-NGcGM3 14F7 monoclonal antibody (mAb) in L1210 murine tumor cell line but not in mouse normal cells (B and CD4(+) T lymphocytes) that expressed the antigen. Impairment of ganglioside synthesis in tumor cells abrogated the 14F7 mAb cytotoxic effect; however, exogenous reincorporation of the ganglioside did not restore tumor cell sensitivity to 14F7 mAb-induced cytotoxicity. 14F7 F(ab')(2) but not Fab fragments retained the cytotoxic capacity of the whole mAb. By contrary, other mAb, which recognizes N-glycolylated gangliosides, did not show any cytotoxic effect. These mAbs showed quite different capacities to bind NGcGM3-positive cell lines measured by binding inhibition experiments. Interestingly, this complement-independent cell death mechanism did not resemble apoptosis, because no DNA fragmentation, caspase activation, or Fas mediation were observed. However, NGcGM3 ganglioside-mediated 14F7 mAb-induced cell death was accompanied by cellular swelling, membrane lesion formation, and cytoskeleton activation, suggesting an oncosis-like phenomenon. This novel mechanism of cell death lets us to support further therapeutic approaches using NGcGM3 as a molecular target for antibody-based cancer immunotherapy.     

Italian oncology nurses' knowledge of complementary and alternative therapies: national survey

Title. Italian oncology nurses’ knowledge of complementary and alternative therapies: national survey. Aim. This paper is a report of a study to investigate the knowledge of Italian oncology nurses in relation to complementary and alternative therapies. Background. In the last decade, the use of complementary and alternative therapies by the general public has increased dramatically. As primary care providers who play a key role in healthcare delivery, it is likely that nurses will be asked about these therapies by their patients. Only if they have an adequate knowledge base, however, can nurses give useful information and counsel patients effectively to allow them to make informed healthcare decisions. Method. A survey was carried out in 2007 with, 270 nurses registered with the Italian Association of Oncology Nursing. A self‐administered questionnaire was used and the response rate was of 57·4% (155/270). Findings. Ninety‐four (60·6%) nurses claimed to have knowledge about complementary and alternative therapies. Over two‐thirds (60·6%, 57/94) reported that books were a primary source of their knowledge. Other common sources included other healthcare workers (50%, 47/94), the Internet (48·9%, 46/94), workshops and seminars (29·8%, 28/94), and formal nursing education (17·0%, 16/94). Only 5·3% (5/94) reported that professional journals were a source of knowledge. During their professional activities, 71·6% (111/155) of the nurses encountered patients using complementary and alternative therapies, while 47·1% (73/155) treated patients asking for information about these techniques. Conclusion. The fact that nurses are responding to demands for these therapies without a solid knowledge base makes it imperative that the nursing curriculum be expanded to include these topics.