Synthetic approaches towards the Lycopodium alkaloids

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/63704The Lycopodium alkaloids are a structurally diverse group of natural products isolated from Lycopodium with important biological effects for the potential treatment of cancer and severe neurodegenerative diseases. To date, full biological studies have been hampered by lack of material from natural sources. Total synthesis represents a possible solution to meet this demand as well as the most effective way to design new compounds to determine structural activity relationships and obtain more potent compounds. The aim of this chapter is to summarise the work carried out in this field so far by presenting an overview of the synthetic strategies used to access each of the four key Lycopodium alkaloid types. Particular emphasis has been placed on methods that rapidly construct each nucleus utilizing tandem reactions

Laparoscopic Management of Chylous Leakage Using a Direct Lymph Node Injection with Methylene Blue as a Leakage Point Location Strategy in a Patient with Retroperitoneal Extragonadal Seminoma

Background: The first-line treatment in cases of chylous leakage is conservative, and operation should be considered only in patients who fail to respond to this treatment. The main clinical concern is the difficulty of intraoperative localization of the site of leakage that can affect surgical outcome. Case Presentation: A 33-year-old man presented with a 4-month history of abdominal pain and weight loss. CT scan revealed enlarged retroperitoneal lymph nodes. Retroperitoneal lymph node biopsy was performed owing to the suspicion of lymphoproliferative disease, with a pathological result of nonspecific adenitis. Because of persistence of pain, an abdominal CT scan showed a large left retroperitoneal fluid collection that was found to be compatible with chyle after drainage. Conservative treatment was established, but because of its failure, surgical management was attempted by the laparoscopic approach. Intraoperative direct lymph node injection of methylene blue was used as a leakage point location strategy that allows selective ligation of the site of leakage. Thereafter a gradual reduction in chyle output to zero was observed. Conclusion: The laparoscopic approach could be a feasible and successful method for the management of chyle leakage in patients refractory to conservative treatment. Intraoperative direct lymph node injection of methylene blue could be a useful technique to facilitate detection of the site of leakage during operation

Validation of the new graded prognostic assessment scale for brain metastases: a multicenter prospective study

<p>Abstract</p> <p>Background</p> <p>Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM). We evaluated the new Graded Prognostic Assessment (GPA) scale in a prospective validation study to compare it with two published prognostic indexes.</p> <p>Methods</p> <p>A total of 285 newly diagnosed BM (<it>n </it>= 85 with synchronous BM) patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 ± 12.0 years. The median KPS and number of BM was 70 (range, 20-100) and 3 (range, 1-50), respectively. The majority of primary tumours were lung (53%), or breast (17%) cancers. Treatment was administered to 255 (89.5%) patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA) 1, 8.4% and Basic Score for BM (BSBM) 3, 9.1%. Mean follow-up (FU) time was 5.2 ± 4.7 months.</p> <p>Results</p> <p>During the period of FU, 225 (78.9%) patients died. The 6 months- and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (<it>P </it>< 0.001), BSBM (<it>P </it>< 0.001), Center (<it>P </it>= 0.007), RPA (<it>P </it>= 0.02) and GPA (<it>P </it>= 0.03) were statistically significant for OS. The survival prediction performances' of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell's concordance indexes <it>C </it>were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively.</p> <p>Conclusions</p> <p>Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability.</p

Laparoscopic Management of Chylous Leakage Using a Direct Lymph Node Injection with Methylene Blue as a Leakage Point Location Strategy in a Patient with Retroperitoneal Extragonadal Seminoma

Background: The first-line treatment in cases of chylous leakage is conservative, and operation should be considered only in patients who fail to respond to this treatment. The main clinical concern is the difficulty of intraoperative localization of the site of leakage that can affect surgical outcome. Case Presentation: A 33-year-old man presented with a 4-month history of abdominal pain and weight loss. CT scan revealed enlarged retroperitoneal lymph nodes. Retroperitoneal lymph node biopsy was performed owing to the suspicion of lymphoproliferative disease, with a pathological result of nonspecific adenitis. Because of persistence of pain, an abdominal CT scan showed a large left retroperitoneal fluid collection that was found to be compatible with chyle after drainage. Conservative treatment was established, but because of its failure, surgical management was attempted by the laparoscopic approach. Intraoperative direct lymph node injection of methylene blue was used as a leakage point location strategy that allows selective ligation of the site of leakage. Thereafter a gradual reduction in chyle output to zero was observed. Conclusion: The laparoscopic approach could be a feasible and successful method for the management of chyle leakage in patients refractory to conservative treatment. Intraoperative direct lymph node injection of methylene blue could be a useful technique to facilitate detection of the site of leakage during operation

Validation of the new graded prognostic assessment scale for brain metastases: a multicenter prospective study

Background: Prognostic indexes are useful to guide tailored treatment strategies for cancer patients with brain metastasis (BM). We evaluated the new Graded Prognostic Assessment (GPA) scale in a prospective validation study to compare it with two published prognostic indexes. Methods: A total of 285 newly diagnosed BM (n = 85 with synchronous BM) patients, accrued prospectively between 2000 and 2009, were included in this analysis. Mean age was 62 +/- 12.0 years. The median KPS and number of BM was 70 (range, 20-100) and 3 (range, 1-50), respectively. The majority of primary tumours were lung (53%), or breast (17%) cancers. Treatment was administered to 255 (89.5%) patients. Only a minority of patients could be classified prospectively in a favourable prognostic class: GPA 3.5-4: 3.9%; recursive partitioning analysis (RPA) 1, 8.4% and Basic Score for BM (BSBM) 3, 9.1%. Mean follow-up (FU) time was 5.2 +/- 4.7 months. Results: During the period of FU, 225 (78.9%) patients died. The 6 months-and 1 year-OS was 36.9% and 17.6%, respectively. On multivariate analysis, performance status (P < 0.001), BSBM (P < 0.001), Center (P = 0.007), RPA (P = 0.02) and GPA (P = 0.03) were statistically significant for OS. The survival prediction performances' of all indexes were identical. Noteworthy, the significant OS difference observed within 3 months of diagnosis between the BSBM, RPA and GPA classes/groups was not observed after this cut-off time point. Harrell's concordance indexes C were 0.58, 0.61 and 0.58 for the GPA, BSBM and RPA, respectively. Conclusions: Our data suggest that the new GPA index is a valid prognostic index. In this prospective study, the prediction performance was as good as the BSBM or RPA systems. These published indexes may however have limited long term prognostication capability

New Generation Pulse Modulation in Holmium:YAG Lasers: A Systematic Review of the Literature and Meta-Analysis

(1) Background: New pulse modulation (PM) technologies in Holmium:YAG lasers are available for urinary stone treatment, but little is known about them. We aim to systematically evaluate the published evidence in terms of their lithotripsy performance. (2) Methods: A systematic electronic search was performed (MEDLINE, Scopus, and Cochrane databases). We included all relevant publications, including randomized controlled trials, non-randomized comparative and non-comparative studies, and in-vitro studies investigating Holmium:YAG lithotripsy performance employing any new PM. (3) Results: Initial search yielded 203 studies; 24 studies were included after selection: 15 in-vitro, 9 in-vivo. 10 In-vitro compared Moses with regular PM, 1 compared Quanta’s, 1 Dornier MedTech’s, 2 Moses with super Thulium Fiber Laser, and 1 compared Moses with Quanta PMs. Six out of seven comparative studies found a statistically significant difference in favor of new-generation PM technologies in terms of operative time and five out of six in fragmentation time; two studies evaluated retropulsion, both in favor of new-generation PM. There were no statistically significant differences regarding stone-free rate, lasing and operative time, and complications between Moses and regular PM when data were meta-analyzed. (4) Conclusions: Moses PM seems to have better lithotripsy performance than regular modes in in-vitro studies, but there are still some doubts about its in-vivo results. Little is known about the other PMs. Although some results favor Quanta PMs, further studies are needed

New Generation Pulse Modulation in Holmium:YAG Lasers : A Systematic Review of the Literature and Meta-Analysis

New pulse modulation (PM) technologies in Holmium:YAG lasers are available for urinary stone treatment, but little is known about them. We aim to systematically evaluate the published evidence in terms of their lithotripsy performance. A systematic electronic search was performed (MEDLINE, Scopus, and Cochrane databases). We included all relevant publications, including randomized controlled trials, non-randomized comparative and non-comparative studies, and in-vitro studies investigating Holmium:YAG lithotripsy performance employing any new PM. Initial search yielded 203 studies; 24 studies were included after selection: 15 in-vitro, 9 in-vivo. 10 In-vitro compared Moses with regular PM, 1 compared Quanta's, 1 Dornier MedTech's, 2 Moses with super Thulium Fiber Laser, and 1 compared Moses with Quanta PMs. Six out of seven comparative studies found a statistically significant difference in favor of new-generation PM technologies in terms of operative time and five out of six in fragmentation time; two studies evaluated retropulsion, both in favor of new-generation PM. There were no statistically significant differences regarding stone-free rate, lasing and operative time, and complications between Moses and regular PM when data were meta-analyzed. Moses PM seems to have better lithotripsy performance than regular modes in in-vitro studies, but there are still some doubts about its in-vivo results. Little is known about the other PMs. Although some results favor Quanta PMs, further studies are needed