3-Alkoxy-1,2-Dioxolanes: Synthesis and Evaluation as Potential Antimalarial Agents

A number of 3-alkoxy-1,2-dioxolanes exhibit promising levels of antimalarial activity against P. falciparum. A new route to the 1,2-dioxolane core is reported based on tandem peroxidation/cyclization of enones.     

Survival Rates and Cause of Death in 174 Patients with Chronic Pancreatitis

Background  The natural history after surgery for chronic pancreatitis is rarely reported. Methods  Between 1970 and 1999, 174 patients underwent surgery for chronic pancreatitis and were followed until December 2006. They were divided in four groups: (1) resection 62; (2) drainage 82; (3) external drainage 7; (4) non-pancreas-directed surgery 23. A second procedure was required by 25 patients and a third by four: group 1 = 6 + 0, group 2 = 10 + 2, group 3 = 3 + 1, group 4 = 6 + 1. Results  Hospital mortality was four of 174 (2.3%). Fifty-seven patients are alive; 49 of 170 developed cancer, and 38 died: lung (22), oral, pharynx, larynx (eight), esophagus, kidney, pancreas, colon, liver (two each), breast, stomach, mediastinum, prostate, melanoma, chronic myelogenous leukemia, squamous cancer of the auricle (one each), liver metastasis from unknown primary (two). Fifteen patients died of liver cirrhosis, 13 of myocardial infarction/decompensation, six of vascular problems, five each of acute renal insufficiency or cerebral diseases, four each of acute pancreatitis, accidental trauma, complications of diabetes, bronchopneumonia, and 19 of other causes. The overall 5-, 10-, 15-, 20-, 25-, and 30-year survival rate was 84.7, 65.6, 51.6, 38.0, 28.1, and 23.5. Conclusions  Incidence of pancreatic cancer was 1.2%. The high incidence of smoking cancers (18.8%) is explained by the smoking habits of almost 100% of our patients. Eliminating smoking and increasing tests on organs at risk may prolong survival. Grant support: This study has been supported by the Ministero dell’Università e Ricerca Scientifica (Cofin 2005060715_001), Rome, Italy.     

Apathy and anhedonia rating scales in Parkinson's disease: Critique and recommendations

Apathy is a common condition in Parkinson's disease (PD) and is generally defined as a lack of motivation. It is associated with more severe cognitive dysfunction and a decrease in activities of daily living (ADL) performance. Anhedonia, the inability to experience pleasure, can be a symptom of both depressive and apathetic syndromes. The Movement Disorder Society (MDS) commissioned a task force to assess the clinimetric properties of apathy and anhedonia scales in PD patients. A systematic literature review was conducted to identify scales that have either been validated or used in PD patients. Apathy scales identified for review include the Apathy Evaluation Scale (AES), the Apathy Scale (AS), the Apathy Inventory (AI), and the Lille Apathy Rating Scale (LARS). In addition, item 4 (motivation/initiative) of the Unified Parkinson's Disease Rating Scale (UPDRS) and item 7 (apathy) of the Neuropsychiatric Inventory (NPI) were included. Anhedonia scales identified for review were the Snaith‐Hamilton Pleasure Scale (SHAPS) and the Chapman scales for physical and social anhedonia. Only the AS is classified as “recommended” to assess apathy in PD. Although item 4 of the UPDRS also meets the criteria to be classified as recommended, it should be considered for screening only because of the obvious limitations of a single item construct. For the assessment of anhedonia, only the SHAPS meets the criteria of “Suggested.” Information on the validity of apathy and anhedonia scales is limited because of the lack of consensus on diagnostic criteria for these conditions. © 2008 Movement Disorder Society     

Cerebromeningeal pleomorphic xanthoastrocytoma. Report on four cases: Clinical,radiologic and pathological features. (Including a case with malignant evolution)

Three cases of cerebromeningeal pleomorphic xanthoastrocytoma are presented and the recurrence of a fourth case, previously described in 1980, is examined because of its evolution towards malignancy.Clinical, radiologic and pathological aspects are discussed and the general features of the previously reported cases of xanthoastrocytoma are reviewed.     

Malignant lentigo-melanoma—A comparative histological and electron microscopy study

We examined, by light and electron microscopy, three cases of malignant lentigo, one of which was in the vertical growth phase. The purpose of our work was to compare the diverse patterns between superficial spreading melanoma and malignant lentigo. The observations suggest the following major findings: 1) the cells of malignant lentigo differ from normal melanocytes, and in the same specimen they differ from one another; 2) in malignant lentigo, melanosomes at stage II-IV are visible; and 3) in spreading melanoma, the melanosomes do not attain complete maturation. These morphological features explain the different behaviour of these two types of tumors.     

Treatment of refractory bleeding after cardiac operations with low-dose recombinant activated factor VII (NovoSeven): a propensity score analysis.

BACKGROUND: Recombinant activated factor VII (rFVIIa) has been increasingly used to stop life-threatening bleeding following cardiac operations. Nonetheless, the issue of dosing, given the expense and potential for thrombotic complications, is still of major concern. We report our experience with small-dose rFVIIa in patients with refractory bleeding after cardiac surgery. METHODS AND RESULTS: From September 2005 to June 2007, 40 patients (mean age 70.1+/-9.2 years, 52.5 males) received a low dose of rFVIIa (median: 18 microg/kg, interquartile range: 9-16 microg/kg) for refractory bleeding after cardiac surgery. Forty propensity score-based greedy matched controls were compared to the study group. Low dose of rFVIIa significantly reduced the 24-h blood loss: 1610 ml [ 1285-1800 ml] versus 3171 ml [2725-3760 ml] in the study and control groups, respectively (p<0.001). Thus, hourly bleeding was 51.1 ml [34.7-65.4 ml] in patients receiving rFVIIa and 196.2 ml/h [142.1-202.9 ml] in controls (p<0.001). Furthermore, patients receiving rFVIIa showed a lower length of stay in the intensive care unit (p<0.001) and shorter mechanical ventilation time (p<0.001). In addition, the use of rFVIIa was associated with reduction of transfusion requirements of red blood cells, fresh frozen plasma and platelets (all, p<0.001). Finally, treated patients showed improved hemostasis with rapid normalization of coagulation variables (partial thromboplastin time, international normalized ratio, platelet count, p<0.001). In contrast, activated prothrombin time and fibrinogen did not differ between groups (p=ns). No thromboembolic-related event was detected in our cohort. CONCLUSIONS: In our experience low-dose rFVIIa was associated with reduced blood loss, improvement of coagulation variables and decreased need for transfusions. Our findings need to be confirmed by further larger studies.     

Redefining the role of interferon in the treatment of malignant diseases

Interferon (IFN) is a cytokine with a long history of use as immunotherapy in the treatment of various solid tumours and haematological malignancies. The initial use of IFN in cancer therapy was based on its antiproliferative and immunomodulatory effects, and it has been shown more recently to have cytotoxic and anti-angiogenic properties. These features make it a rational anticancer therapy; however, advances in our understanding of the molecular mechanisms involved in cancer development and growth and the availability of effective, alternative therapies have led to IFN therapy being superseded in many cancers. IFN is still commonly used in renal cell carcinoma (RCC), melanoma and myeloproliferative disorders, in which its optimal dose and treatment duration remain to be established despite extensive clinical experience. Preclinical studies of the mechanism of action of IFN suggest that different antitumour effects are relevant at different doses, providing a rationale to explore the use of different dose regimens of IFN, particularly when combined with other therapies. In particular, the advent of novel anti-angiogenic therapies in RCC means that the role of IFN needs to be re-examined with a focus on how best to maximise efficacy and minimise toxicity when used with these agents. This review will focus on the therapeutic use of IFN in these disorders, provide an overview of available data and consider what the data suggest regarding the potential optimal use of IFN in the future.