Pemetrexed safety and pharmacokinetics in patients with third-space fluid

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Dickgreber, Nicolas J; Sorensen, Jens Benn; Paz-Ares, Luis G

2010-01-01

Pemetrexed is established as first-line treatment with cisplatin for malignant pleural mesothelioma and advanced nonsquamous non-small-cell lung cancer (NSCLC) and as single-agent second-line treatment for nonsquamous NSCLC. Because the structure and pharmacokinetics of pemetrexed are similar to ...... to those of methotrexate, and methotrexate is associated with severe toxicity in patients with third-space fluid (TSF), the safety of pemetrexed in patients with TSF was evaluated....

First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study.

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Shi, Y K; Wang, L; Han, B H; Li, W; Yu, P; Liu, Y P; Ding, C M; Song, X; Ma, Z Y; Ren, X L; Feng, J F; Zhang, H L; Chen, G Y; Han, X H; Wu, N; Yao, C; Song, Y; Zhang, S C; Song, W; Liu, X Q; Zhao, S J; Lin, Y C; Ye, X Q; Li, K; Shu, Y Q; Ding, L M; Tan, F L; Sun, Y

2017-10-01

Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation. Eligible participants were adults with stage IIIB/IV lung adenocarcinoma and exon 19/21 EGFR mutations. Participants were randomly allocated (1 : 1) to receive oral icotinib or 3-week cycle of cisplatin plus pemetrexed for up to four cycles; non-progressive patients after four cycles were maintained with pemetrexed until disease progression or intolerable toxicity. The primary end point was progression-free survival (PFS) assessed by independent response evaluation committee. Other end points included overall survival (OS) and safety. Between January 2013 and August 2014, 296 patients were randomized, and 285 patients were treated (148 to icotinib, 137 to chemotherapy). Independent response evaluation committee-assessed PFS was significantly longer in the icotinib group (11.2 versus 7.9 months; hazard ratio, 0.61, 95% confidence interval 0.43-0.87; P = 0.006). No significant difference for OS was observed between treatments in the overall population or in EGFR-mutated subgroups (exon 19 Del/21 L858R). The most common grade 3 or 4 adverse events (AEs) in the icotinib group were rash (14.8%) and diarrhea (7.4%), compared with nausea (45.9%), vomiting (29.2%), and neutropenia (10.9%) in the chemotherapy group. AEs (79.1% versus 94.2%; P icotinib group than in the chemotherapy group. First-line icotinib significantly improves PFS of advanced lung adenocarcinoma patients with EGFR mutation with a tolerable and manageable safety profile. Icotinib should be considered as a first-line treatment for this patient population. © The Author

Critical appraisal of pemetrexed in the treatment of NSCLC and metastatic pulmonary nodules

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Li X

2014-06-01

Full Text Available Xin Li, Sen Wei, Jun ChenTianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Heping District, Tianjin, People's Republic of ChinaAbstract: Pemetrexed, a new multitarget antifolate antineoplastic agent, has significantly improved the overall survival in nonsquamous non-small-cell lung cancer patients. Presently, pemetrexed is recommended for first line treatment in combination with platinum derivatives, for second line treatment as a single agent and, more recently, as maintenance treatment after first line chemotherapy. In this article we critically appraise the status of pemetrexed including pharmacodynamics, pharmacokinetics, toxicity, and the cost effectiveness of pemetrexed, as well as the predictive biomarkers for pemetrexed based chemotherapy.Keywords: chemotherapy, non-small-cell lung cancer, pemetrexed

c-FLIP and the NOXA/Mcl-1 axis participate in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells.

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Zhao, Xiaofei; Kong, Feng; Wang, Lei; Zhang, Han

2017-01-01

Choroidal melanoma is the most common primary malignant intraocular tumor, and very few effective therapies are available to treat it. Our study aimed to understand whether pemetrexed plus cisplatin exerts a beneficial synergistic effect in human choroidal melanoma cells and to delineate the underlying molecular mechanism. To accomplish these aims, we treated choroidal melanoma cells with pemetrexed and cisplatin and assessed cell survival with SRB and MTT assays. Proteins were detected using western blotting analysis. NOXA and CHOP were knocked down with siRNA. We found that pemetrexed or cisplatin alone inhibited survival and induced apoptosis in human choroidal melanoma cells. Furthermore, the expression levels of c-FLIP, an anti-apoptotic protein in the extrinsic apoptosis pathway, and Mcl-1, an anti-apoptotic protein in the intrinsic apoptosis pathway, were decreased by pemetrexed or cisplatin respectively, while the expression of a pro-apoptotic protein in the intrinsic apoptosis pathway, NOXA, was up-regulated. Moreover, pemetrexed or cisplatin alone increased the protein expression of the endoplasmic reticulum stress markers IRE1α, Bip and CHOP. Silencing CHOP expression reduced NOXA expression. These findings suggest that the pemetrexed or cisplatin induced intrinsic apoptosis via activation of the ER stress response. Importantly, combining the two compounds more strongly induced apoptosis. Following the cotreatment, CHOP and NOXA expression increased, while c-FLIP and Mcl-1 expression decreased, and these effects were more pronounced than when using either compound alone. This result suggests that pemetrexed and cisplatin synergistically activate ER stress response-induced apoptosis in choroidal melanoma cells. To summarize, the c-FLIP and NOXA/Mcl-1 axis participated in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells. Intrinsic apoptosis was induced via activation of the ER stress response. Our study provides

Sequential treatment of icotinib after first-line pemetrexed in advanced lung adenocarcinoma with unknown EGFR gene status.

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Zheng, Yulong; Fang, Weijia; Deng, Jing; Zhao, Peng; Xu, Nong; Zhou, Jianying

2014-07-01

In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is an important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors (TKI) in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS. We analyzed 38 patients with advanced lung adenocarcinoma with UN-EGFR-GS treated with first-line pemetrexed-based chemotherapy followed by icotinib as maintenance or second-line therapy. The response rates to pemetrexed and icotinib were 21.1% and 42.1%, respectively. The median overall survival was 27.0 months (95% CI, 19.7-34.2 months). The 12-month overall survival probability was 68.4%. The most common toxicities observed in icotinib phase were rashes, diarrheas, and elevated aminotransferase. Subgroup analysis indicated that the overall survival is correlated with response to icotinib. The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China.

Pemetrexed safety and pharmacokinetics in patients with third-space fluid

DEFF Research Database (Denmark)

Dickgreber, Nicolas J; Sørensen, Jens Benn; Paz-Ares, Luis G

2010-01-01

Pemetrexed is established as first-line treatment with cisplatin for malignant pleural mesothelioma and advanced nonsquamous non-small-cell lung cancer (NSCLC) and as single-agent second-line treatment for nonsquamous NSCLC. Because the structure and pharmacokinetics of pemetrexed are similar...

Pharmacokinetic evaluation of pemetrexed

DEFF Research Database (Denmark)

Sørensen, Jens Benn

2011-01-01

correlates with renal function and it may be safely used with vitamin supplementation in patients with creatinine clearance ≥ 45 ml/min. The pharmacokinetics of pemetrexed is also largely unchanged in third-space fluids and can be feasibly and safely administered in combination with several other cytotoxic...

Pharmacokinetic evaluation of pemetrexed

DEFF Research Database (Denmark)

Sørensen, Jens Benn

2011-01-01

correlates with renal function and it may be safely used with vitamin supplementation in patients with creatinine clearance = 45 ml/min. The pharmacokinetics of pemetrexed is also largely unchanged in third-space fluids and can be feasibly and safely administered in combination with several other cytotoxic...

Phase II Study of Biweekly Pemetrexed Plus Irinotecan as Second-Line Therapy for Metastatic Colorectal Cancer

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C. Louvet

2010-01-01

Conclusion. Pemetrexed plus irinotecan administered every two weeks is an active and well-tolerated regimen in mCRC patients pretreated with FOLFOX regimen. However, this regimen does not seem to provide clinically relevant advantage over historical data of a classical FOLFIRI regimen.

Pemetrexed plus carboplatin versus pemetrexed in pretreated patients with advanced non-squamous non-small-cell lung cancer : treating the right patients based on individualized treatment effect prediction

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van Kruijsdijk, R. C. M.; Visseren, F. L. J.; Boni, L.; Groen, H. J. M.; Dingemans, A. M. C.; Aerts, J. G. J. V.; van der Graaf, Y.; Ardizzoni, A.; Smit, E. F.

In this study, it is shown that there is important heterogeneity in the effects of pemetrexed-carboplatin versus pemetrexed on progression-free survival in pretreated patients with advanced non-squamous non-small-cell lung cancer. Treatment effect can be predicted for individual patients using a

Schedule-dependent cytotoxic synergism of pemetrexed and erlotinib in BXPC-3 and PANC-1 human pancreatic cancer cells.

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Wang, Lin; Zhu, Zhi-Xia; Zhang, Wen-Ying; Zhang, Wei-Min

2011-09-01

Previous studies have shown that both pemetrexed, a cytotoxic drug, and erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), inhibit the cell growth of pancreatic cancer cells. However, whether they exert a synergistic antitumor effect on pancreatic cancer cells remains unknown. The present study aimed to assess the synergistic effect of erlotinib in combination with pemetrexed using different sequential administration schedules on the proliferation of human pancreatic cancer BXPC-3 and PANC-1 cells and to probe its cellular mechanism. The EGFR and K-ras gene mutation status was examined by quantitative PCR high-resolution melting (qPCR-HRM) analysis. BXPC-3 and PANC-1 cells were incubated with pemetrexed and erlotinib using different administration schedules. MTT assay was used to determine cytotoxicity, and cell cycle distribution was determined by flow cytometry. The expression and phosphorylation of EGFR, HER3, AKT and MET were determined using Western blotting. Both pemetrexed and erlotinib inhibited the proliferation of BXPC-3 and PANC-1 cells in a dose- and time-dependent manner in vitro. Synergistic effects on cell proliferation were observed when pemetrexed was used in combination with erlotinib. The degree of the synergistic effects depended on the administration sequence, which was most obvious when erlotinib was sequentially administered at 24-h interval following pemetrexed. Cell cycle studies revealed that pemetrexed induced S arrest and erlotinib induced G(0)/G(1) arrest. The sequential administration of erlotinib following pemetrexed induced S arrest. Western blot analyses showed that pemetrexed increased and erlotinib decreased the phosphorylation of EGFR, HER3 and AKT, respectively. However, both pemetrexed and erlotinib exerted no significant effects on the phosphorylation of c-MET. The phosphorylation of EGFR, HER3 and AKT was significantly suppressed by scheduled incubation with pemetrexed followed by erlotinib

Home administration of maintenance pemetrexed for patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and phase II feasibility study design.

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Lal, Rohit; Bourayou, Nawel; Hillerdal, Gunnar; Nicolson, Marianne; Vikstrom, Anders; Lorenzo, Maria; D'yachkova, Yulia; Barriga, Susana; Visseren-Grul, Carla

2013-10-03

Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting. Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0-1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m(2) every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients' quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011. This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home-based chemotherapy. The study design

Maximizing Benefits from Maintenance Pemetrexed with Stereotactic Ablative Radiotherapy in Oligoprogressive Non-Squamous Non-Small Cell Lung Cancer

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Shao-Lun Lu

2016-08-01

Full Text Available Maintenance pemetrexed offers survival benefit with well-tolerated toxicities for advanced non-squamous non-small cell lung cancer (NSCLC. We present 3 consecutively enrolled patients with advanced non-squamous NSCLC, receiving stereotactic ablative radiotherapy (SABR for oligoprogressive disease during maintenance pemetrexed. All of them had sustained local control of thoracic oligoprogression after the SABR, while maintenance pemetrexed were kept for additionally long progression-free interval. SABR targeting oligoprogression with continued pemetrexed is an effective and safe approach to extend exposure of maintenance pemetrexed, thus maximizing the benefit from it.

Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3.

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Ikemura, Kenji; Hamada, Yugo; Kaya, Chinatsu; Enokiya, Tomoyuki; Muraki, Yuichi; Nakahara, Hiroki; Fujimoto, Hajime; Kobayashi, Tetsu; Iwamoto, Takuya; Okuda, Masahiro

2016-10-01

Pemetrexed, a multitargeted antifolate, is eliminated by tubular secretion via human organic anion transporter 3 (hOAT3). Although proton pump inhibitors (PPIs) are frequently used in cancer patients, the drug interaction between PPIs and pemetrexed remains to be clarified. In this study, we examined the drug interaction between pemetrexed and PPIs in hOAT3-expressing cultured cells, and retrospectively analyzed the impact of PPIs on the development of hematologic toxicity in 108 patients who received pemetrexed and carboplatin treatment of nonsquamous non-small cell lung cancer for the first time between January 2011 and June 2015. We established that pemetrexed was transported via hOAT3 (Km = 68.3 ± 11.1 µM). Lansoprazole, rabeprazole, pantoprazole, esomeprazole, omeprazole, and vonoprazan inhibited hOAT3-mediated uptake of pemetrexed in a concentration-dependent manner. The inhibitory effect of lansoprazole was much greater than those of other PPIs and the apparent IC50 value of lansoprazole against pemetrexed transport via hOAT3 was 0.57 ± 0.17 µM. The inhibitory type of lansoprazole was competitive. In a retrospective study, multivariate analysis revealed that coadministration of lansoprazole, but not other PPIs, with pemetrexed and carboplatin was an independent risk factor significantly contributing to the development of hematologic toxicity (odds ratio: 10.004, P = 0.005). These findings demonstrated that coadministration of lansoprazole could exacerbate the hematologic toxicity associated with pemetrexed, at least in part, by competitive inhibition of hOAT3. Our results would aid clinicians to make decisions of coadministration drugs to avoid drug interaction-induced side effects for achievement of safe and appropriate chemotherapy with pemetrexed. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Sequentially administrated of pemetrexed with icotinib/erlotinib in lung adenocarcinoma cell lines in vitro.

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Feng, Xiuli; Zhang, Yan; Li, Tao; Li, Yu

2017-12-26

Combination of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) had been proved to be a potent anti-drug for the treatment of tumors. However, survival time was not extended for the patients with lung adenocarcinoma (AdC) compared with first-line chemotherapy. In the present study, we attempt to assess the optimal schedule of the combined administration of pemetrexed and icotinib/erlotinib in AdC cell lines. Human lung AdC cell lines with wild-type (A549), EGFR T790M (H1975) and activating EGFR mutation (HCC827) were applied in vitro to assess the differential efficacy of various sequential regimens on cell viability, cell apoptosis and cell cycle distribution. The results suggested that the antiproliferative effect of the sequence of pemetrexed followed by icotinib/erlotinib was more effective than that of icotinib/erlotinib followed by pemetrexed. Additionally, a reduction of G1 phase and increased S phase in sequence of pemetrexed followed by icotinib/erlotinib was also observed, promoting cell apoptosis. Thus, the sequential administration of pemetrexed followed by icotinib/erlotinib exerted a synergistic effect on HCC827 and H1975 cell lines compared with the reverse sequence. The sequential treatment of pemetrexed followed by icotinib/erlotinib has been demonstrated promising results. This treatment strategy warrants further confirmation in patients with advanced lung AdC.

Phase I Trial of Radiation With Concurrent and Consolidation Pemetrexed and Cisplatin in Patients With Unresectable Stage IIIA/B Non-Small-Cell Lung Cancer

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Brade, Anthony; Bezjak, Andrea; MacRae, Robert; Laurie, Scott; Sun, Alex; Cho, John; Leighl, Natasha; Pearson, Shannon; Southwood, Bernadette; Wang, Lisa; McGill, Shauna; Iscoe, Neill; Shepherd, Frances A.

2011-01-01

Purpose: To evaluate the feasibility and safety of concurrent pemetrexed/cisplatin/thoracic radiotherapy followed by consolidation pemetrexed/cisplatin for unresectable Stage IIIA/B non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible patients with 2 on Days 1 and 22 for Dose Levels 1, 2, and 3/4, respectively) and cisplatin (25 mg/m 2 Days 1-3 for Dose Levels 1-3; 20 mg/m 2 Days 1-5 for Dose Level 4) concurrent with thoracic radiation (61-66 Gy in 31-35 fractions). Consolidation consisted of two cycles of pemetrexed/cisplatin (500 mg/m 2 , 75 mg/m 2 ) 21 days apart, after concurrent therapy. Results: Between January 2006 and October 2007, 16 patients entered the study. Median follow-up was 17.2 months. No dose-limiting toxicities were observed. Median radiation dose was 64 Gy (range, 45-66 Gy). Rates of significant Grade 3/4 hematologic toxicity were 38% and 7%, respectively. One patient experienced Grade 3 acute esophagitis, and 2 experienced late (Grade 3) esophageal stricture, successfully managed with dilation. One patient experienced Grade 3 pneumonitis. The overall response rate was 88%. One-year overall survival was 81%. Conclusions: Full systemic dose pemetrexed seems to be safe with full-dose cisplatin and thoracic radiation in Stage IIIA/B NSCLC. Pemetrexed is the first third-generation cytotoxic agent tolerable at full dose in this setting. A Phase II study evaluating Dose Level 4 is ongoing.

Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells.

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Küçüktürkmen, Berrin; Devrim, Burcu; Saka, Ongun M; Yilmaz, Şükran; Arsoy, Taibe; Bozkir, Asuman

2017-01-01

Combination therapy using anticancer drugs and nucleic acid is a more promising strategy to overcome multidrug resistance in cancer and to enhance apoptosis. In this study, lipid-polymer hybrid nanoparticles (LPNs), which contain both pemetrexed and miR-21 antisense oligonucleotide (anti-miR-21), have been developed for treatment of glioblastoma, the most aggressive type of brain tumor. Prepared LPNs have been well characterized by particle size distribution and zeta potential measurements, determination of encapsulation efficiency, and in vitro release experiments. Morphology of LPNs was determined by transmission electron microscopy. LPNs had a hydrodynamic size below 100 nm and exhibited sustained release of pemetrexed up to 10 h. Encapsulation of pemetrexed in LPNs increased cellular uptake from 6% to 78%. Results of confocal microscopy analysis have shown that co-delivery of anti-miR-21 significantly improved accumulation of LPNs in the nucleus of U87MG cells. Nevertheless, more effective cytotoxicity results could not be obtained due to low concentration of anti-miR-21, loaded in LPNs. We expect that the effective drug delivery systems can be obtained with higher concentration of anti-miR-21 for the treatment of glioblastoma.

Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

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Weiss, Glen J; Donehower, Ross C; Iyengar, Tara; Ramanathan, Ramesh K; Lewandowski, Karen; Westin, Eric; Hurt, Karla; Hynes, Scott M; Anthony, Stephen P; McKane, Scott

2013-02-01

This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40-195 mg/m(2)) were combined with 500 mg/m(2) of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Antitumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. A total of 31 patients were enrolled into six cohorts (three at 40 mg/m(2) over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m(2), 70 mg/m(2), and 195 mg/m(2); 13 at 105 mg/m(2); six at 150 mg/m(2)). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m(2)); reversible infusion-related reaction (150 mg/m(2)); thrombocytopenia (195 mg/m(2)); and fatigue (195 mg/m(2)). The maximum tolerated dose was defined as 150 mg/m(2). The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m(2). LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles.

Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China.

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Lu, Shun; Ye, Ming; Ding, Lieming; Tan, Fenlai; Fu, Jie; Wu, Bin

2017-02-07

Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy.

Pemetrexed-carboplatin with intercalated icotinib in the treatment of patient with advanced EGFR wild-type lung adenocarcinoma

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Xu, Tongpeng; Wu, Hao; Jin, Shidai; Min, Huang; Zhang, Zhihong; Shu, Yongqian; Wen, Wei; Guo, Renhua

2017-01-01

Abstract Rationale: Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. Patient concerns: Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. Diagnoses: We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib. Interventions: In this case, we reported the successful long-term maintenance treatment of a patient with EGFR wt NSCLC with pemetrexed and Icotinib. The patient (40-year-old female) was found with ovarian masses and lung masses. Pathological, immunohistochemical, and amplification refractory mutation system (ARMS) assay examinations of ovarian specimen suggested the expression of metastatic lung adenocarcinoma with wt EGFR. After failure treatment with paclitaxel-carboplatin, the patient received 4 cycles of pemetrexed plus platinum with intercalated icotinib and then remained on pemetrexed and icotinib. Outcomes: A partial response was achieved after the treatment. The patient's condition had remained stable on pemetrexed and icotinib for more than 20 months, with no evidence of progression. Lessons: To our knowledge, this is the first report using the long-term maintenance treatment with pemetrexed and intercalated icotinib in EGFR wt patient. The therapeutic strategies warrant further exploration in selected populations of NSCLC. PMID:28816950

FLT-PET/CT as a Biomarker of Therapeutic Response in Pemetrexed Therapy for Non-Small Cell Lung Cancer

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2016-12-01

Teva Pharmaceuticals , Petach Tikva Israel) were provided freshly prepared as a 1mg/ml sterile saline solution by the Abramson Cancer Center...human and murine, pemetrexed (ALIMTA; Eli Lilly and Company, Indianapolis, IN) and cisplatin (Teva Pharmaceuticals , PetachTikva Israel) were provided...Griffiths JR, Doblas S, Sinkus R, Laverman P, Oyen WJ, Heerschap A, Boerman OC. Response Monitoring with [18F]FLT PET and Diffusion-Weighted MRI

Second-Line Therapy for Advanced NSCLC.

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Weiss, Jared M; Stinchcombe, Thomas E

2013-01-01

Most patients with lung cancer have non-small cell lung cancer (NSCLC) subtype and have advanced disease at the time of diagnosis. Improvements in both first-line and subsequent therapies are allowing longer survival and enhanced quality of life for these patients. The median overall survival observed in many second-line trials is approximately 9 months, and many patients receive further therapy after second-line therapy. The cytotoxic agents pemetrexed and docetaxel and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are standard second-line therapies. For patients with EGFR mutation, a TKI is the favored second-line therapy if not already used in first-line therapy. For patients without the EGFR mutation, TKIs are an option, but many oncologists favor cytotoxic therapy. The inhibitor of the EML4/ALK fusion protein, crizotinib, has recently become a standard second-line treatment for patients with the gene rearrangement and has promise for patients with the ROS1 rearrangement.

A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients.

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Davies, Janine M; Dhruva, Nirav S; Walko, Christine M; Socinski, Mark A; Bernard, Stephen; Hayes, D Neil; Kim, William Y; Ivanova, Anastasia; Keller, Kimberly; Hilbun, Layla R; Chiu, Michael; Dees, E Claire; Stinchcombe, Thomas E

2011-02-01

Sorafenib has demonstrated single agent activity in non-small cell (NSCLC) and small cell lung cancer (SCLC). Carboplatin/pemetrexed (CbP) and cisplatin/etoposide (PE) are commonly used in the treatment of these diseases. A phase I trial escalating doses of sorafenib in combination with fixed doses of PE (Arm A) or CbP (Arm B) was performed using a 3-patient cohort design to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT); DLT were assessed in the first cycle. The trial was subsequently amended with closure of Arm B and to include Arm C with a reduced dose of carboplatin. Between 9/2007 and 9/2008, 20 pts were treated on the trial; median age 62 (range 42-73), male/female ratio 12/8, PS 0/1 ratio 6/14, and median number of prior therapies 2 (range 1-4). The most common tumor types were NSCLC and SCLC. On Arm A at dose level 0 (sorafenib 200 mg BID), 2 of 4 patients experienced DLT; 2 patients were enrolled at dose level -1 (sorafenib 200 mg QD) without DLT, but this arm was closed due to slow accrual. On Arm B, 2 of 3 patients experienced DLT at dose level 0 (sorafenib 200 mg BID). On Arm C at dose level 0 (sorafenib 200 mg BID), 1 of 6 patients experienced DLT, and at dose level +1 (sorafenib 400 mg BID) 2 of 5 patients experienced a DLT. The MTD of sorafenib was 200 mg BID continuously in combination with carboplatin (AUC of 5) and pemetrexed 500 mg/m² every 3 weeks. However, only 6 patients were treated at this dose level, and the results should be interpreted cautiously. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Adjuvant Bidirectional Chemotherapy with Intraperitoneal Pemetrexed Combined with Intravenous Cisplatin for Diffuse Malignant Peritoneal Mesothelioma

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Lana Bijelic

2012-01-01

Full Text Available Cytoreductive surgery (CRS with heated intraoperative intraperitoneal chemotherapy (HIPEC has emerged as optimal treatment for diffuse malignant peritoneal mesothelioma (DMPM showing median survivals of 36–92 months. However, recurrences occur frequently even in patients undergoing optimal cytreduction and are often confined to the abdomen. We initiated a Phase II study of adjuvant intraperitoneal pemetrexed combined with intravenous cisplatin for patients undergoing CRS and HIPEC for DMPM. The treatment consisted of pemetrexed 500 mg/m2 intraperitoneally and cisplatin 50 mg/m2 intravenously given simultaneously on day 1 of every 21 day cycle for 6 cycles. The primary endpoint of the study was treatment related toxicity. From July 2007 until July 2009 ten patients were enrolled. Nine of 10 completed all 6 cycles of adjuvant treatment per protocol. The most common toxicities were fatigue, nausea and abdominal pain grade 1 or 2. There was one grade 3 toxicity consisting of a catheter infection. The median survival for all 10 patients was 33.5 months. Pharmacokinetic analysis of intraperitoneal pemetrexed showed a peritoneal to plasma area under the curve ratio of 70. Our study shows that adjuvant intravenous cisplatin and intraperitoneal pemetrexed can be used following CRS and HIPEC for DMPM with low morbidity.

Pemetrexed-carboplatin with intercalated icotinib in the treatment of patient with advanced EGFR wild-type lung adenocarcinoma: A case report.

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Xu, Tongpeng; Wu, Hao; Jin, Shidai; Min, Huang; Zhang, Zhihong; Shu, Yongqian; Wen, Wei; Guo, Renhua

2017-08-01

Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib. In this case, we reported the successful long-term maintenance treatment of a patient with EGFR wt NSCLC with pemetrexed and Icotinib. The patient (40-year-old female) was found with ovarian masses and lung masses. Pathological, immunohistochemical, and amplification refractory mutation system (ARMS) assay examinations of ovarian specimen suggested the expression of metastatic lung adenocarcinoma with wt EGFR. After failure treatment with paclitaxel-carboplatin, the patient received 4 cycles of pemetrexed plus platinum with intercalated icotinib and then remained on pemetrexed and icotinib. A partial response was achieved after the treatment. The patient's condition had remained stable on pemetrexed and icotinib for more than 20 months, with no evidence of progression. To our knowledge, this is the first report using the long-term maintenance treatment with pemetrexed and intercalated icotinib in EGFR wt patient. The therapeutic strategies warrant further exploration in selected populations of NSCLC.

Comparison of erlotinib and pemetrexed as second-/third-line treatment for lung adenocarcinoma patients with asymptomatic brain metastases

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He YY

2016-04-01

Full Text Available Yayi He,1,* Wenwen Sun,2,* Yan Wang,3,* Shengxiang Ren,1 Xuefei Li,3 Jiayu Li,3 Christopher J Rivard,4 Caicun Zhou,1 Fred R Hirsch4 1Department of Oncology, Shanghai Pulmonary Hospital, 2Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, 3Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, USA *These authors contributed equally to this work Objective: Brain metastases occur in one-third of all non-small-cell lung cancer patients. Due to restrictive transport at the blood–brain barrier, many drugs provide poor control of metastases in the brain. The aim of this study was to compare erlotinib with pemetrexed as second-/third-line treatment in patients with lung adenocarcinoma with asymptomatic brain metastases.Methods: From January 2012 to June 2014, all lung adenocarcinoma patients with asymptomatic brain metastases who received treatment with erlotinib or pemetrexed as second-/third-line treatment were retrospectively reviewed. Chi-square and log-rank tests were used to perform statistical analysis.Results: The study enrolled 99 patients, of which 44 were positive for EGFR mutation. Median progression-free survival (PFS in months was not significantly different between the erlotinib- and pemetrexed-treated groups (4.2 vs 3.4 months; 95% confidence interval [CI]: 2.01–6.40 vs 2.80–5.00, respectively; P=0.635. Median PFS was found to be significantly longer in EGFR mutation–positive patients in the erlotinib-treated group (8.0 months; 95% CI 5.85–10.15 compared to the pemetrexed group (3.9 months; 95% CI: 1.25–6.55; P=0.032. The most common treatment-related side effect was mild-to-moderate rash and the most common drug-related side

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

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Treat Joseph

2011-02-01

Full Text Available Abstract Background This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week pemetrexed given concurrently with radiotherapy (XRT for locally advanced and oligometastatic non-small cell lung cancer (NSCLC. Methods Eligible patients had Stage III or IV (oligometastatic NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6 during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1 of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT in dose level 1, an amended dose level (level 1A continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6 and pemetrexed (500 mg/m2 q3 weeks × 2 -3 cycles. Results Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis. There was one DLT (grade 5 pneumonitis in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease, the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated in stage III patients. Conclusions Concurrent carboplatin with dose-dense (q2week pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC. Trial Registration ClinicalTrials.gov NCT00330044

Pretreatment Red Blood Cell Total Folate Concentration Is Associated With Response to Pemetrexed in Stage IV Nonsquamous Non-Small-cell Lung Cancer.

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Bagley, Stephen J; Vitale, Steven; Zhang, Suhong; Aggarwal, Charu; Evans, Tracey L; Alley, Evan W; Cohen, Roger B; Langer, Corey J; Blair, Ian A; Vachani, Anil; Whitehead, Alexander S

2017-03-01

Pemetrexed inhibits folate-dependent enzymes involved in pyrimidine and purine synthesis. Previous studies of genetic variation in these enzymes as predictors of pemetrexed efficacy have yielded inconsistent results. We investigated whether red blood cell (RBC) total folate, a phenotypic rather than genotypic, marker of cellular folate status was associated with the response to pemetrexed-based chemotherapy in advanced nonsquamous non-small-cell lung cancer (NSCLC). We conducted a prospective cohort study of patients with stage IV nonsquamous NSCLC receiving first-line chemotherapy containing pemetrexed. The pretreatment RBC total folate level was quantified using liquid chromatography mass spectrometry. We then compared the objective response rate (ORR) between patients with RBC total folate concentrations greater than and less than an optimal cutoff value determined from the receiver operating characteristic curve. A logistic regression model was used to adjust for age, sex, and the use of bevacizumab. The ORR was 62% (32 of 52 patients). Receiver operating characteristic analysis was used to establish that a RBC total folate cutoff value of 364.6 nM optimally discriminated between pemetrexed responders and nonresponders. Patients with RBC total folate  364.5 nM (P = .01). This difference persisted after adjusting for age, sex, and the use of bevacizumab (odds ratio, 0.07; 95% confidence interval, 0.01-0.57; P = .01). A low pretreatment RBC total folate was associated with an inferior response to pemetrexed-based chemotherapy in stage IV nonsquamous NSCLC. Larger, multicenter studies are needed to validate RBC total folate as a predictive marker of pemetrexed response. Copyright © 2016 Elsevier Inc. All rights reserved.

Budget impact analysis of pemetrexed introduction: case study from a teaching hospital perspective, Thailand.

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Chanjaruporn, Farsai; Roughead, Elizabeth E; Sooksriwong, Cha-oncin; Kaojarern, Sming

2011-09-01

Thailand does not currently require Budget Impact Analysis (BIA) assessment. The present study aimed to estimate the annual drug cost and the incremental impact on the hospital pharmaceutical budget of the introduction of pemetrexed to a Thai teaching hospital. The budget impact model was conducted in accordance with the Guidelines for preparing submissions to the Pharmaceutical Benefits Advisory Committee (PBAC). The model variables consisted of number of patients, growth rate of lung cancer, uptake rate of pemetrexed over time, unit prices of drugs, and the length and cost of treatment. Sensitivity analysis was performed to determine changes in budgetary impact due to variation of parameters or assumptions in the model. The introduction of pemetrexed was estimated to cause considerable costs for the teaching hospital. In the base-case analysis, the incremental costs were estimated at 8,553,984 Baht in the first year increasing to 12, 118, 144 Baht, 17,820,800 Baht and 17,820,800 Baht in the following years. The 4-year net budgetary impact was 20,154,480 Baht or approximately 127,560 Baht per patient. Sensitivity analyses found that number of treatment cycles andproportion of patients assumed to be treated with pemetrexed were the two most important influencing factors in the model. New costly innovative interventions should be evaluated using the BIA model to determine whether they are affordable. The Thai government should consider requiring the BIA study as one of the requirements for drug submission to assist in the determination of listing and subsidizing decision for medicines.

Analisi di costo di pemetrexed vs docetaxel nel trattamento di seconda linea del carcinoma polmonare non a piccole cellule

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Roberto Ravasio

2005-06-01

Full Text Available OBJECTIVES: to compare costs of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy paying special attention to the adverse events. MATERIALS AND METHODS: a cost analysis was carried out performing comparison between pemetrexed and docetaxel. Clinical data (overall survival and resource consumption (chemotherapy drugs, G-CSF, and hospitalizations due to adverse events were obtained from a randomized phase III trial. The economic evaluation was based on direct costs using local Italian unit costs (euro 2005. The perspective was the National Health Service’s. RESULTS: the study results showed that mean survival of pemetrexed (8,3 months; 0,69 years was higher than mean survival of docetaxel (7,9 months; 0,66 years. The mean cost of treatment with pemetrexed was 8.684,26 euros and with docetaxel was 6.182,87 euros. This difference was nearly offset by the difference in the costs of adverse events: the mean cost of adverse events due to chemotherapy treatment with pemetrexed (493,93 euros turned out to be lower than with docetaxel (2.394,34 euros. CONCLUSION: the present cost-analysis could be a stable ground for a further cost-utility analysis, aimed at reaching a more cost-effectiveness management of the chemotherapy-related adverse effects in patients with NSCLC.

Pretreatment red blood cell total folate is associated with response to pemetrexed in stage IV non-squamous non-small-cell lung cancer

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Bagley, Stephen J.; Vitale, Steven; Zhang, Suhong; Aggarwal, Charu; Evans, Tracey L.; Alley, Evan W.; Cohen, Roger B.; Langer, Corey J.; Blair, Ian A.; Vachani, Anil; Whitehead, Alexander S.

2016-01-01

Objectives Pemetrexed inhibits folate-dependent enzymes involved in pyrimidine and purine synthesis. Prior studies of genetic variation in these enzymes as predictors of pemetrexed efficacy have yielded inconsistent results. We investigated whether red blood cell (RBC) total folate, a phenotypic rather than genotypic marker of cellular folate status, was associated with response to pemetrexed-based chemotherapy in advanced non-squamous non-small-cell lung cancer (NSCLC). Materials and methods We conducted a prospective cohort study of patients with stage IV non-squamous NSCLC receiving first-line chemotherapy containing pemetrexed. Pretreatment RBC total folate was quantified using liquid chromatography/mass spectrometry. We then compared objective response rate (ORR) between patients with RBC total folate concentrations above and below an optimal cut-off value determined from the receiver operating characteristic (ROC) curve. A logistic regression model was used to adjust for age, sex, and use of bevacizumab. Results The ORR was 62% (32 of 52 patients). ROC analysis was used to establish that a RBC total folate cutoff value of 364.6 nM optimally discriminated between pemetrexed responders and non-responders. Patients with RBC total folate below 364.5 nM had an ORR of 27%, compared to 71% in patients with RBC total folate above this value (p=0.01). This difference persisted after adjusting for age, sex, and use of bevacizumab (OR 0.07, 95% CI 0.01 - 0.57, p=0.01). Conclusions Low pretreatment RBC total folate is associated with inferior response to pemetrexed-based chemotherapy in stage IV non-squamous NSCLC. Larger, multicenter studies are needed to validate RBC total folate as a predictive marker of pemetrexed response. PMID:27863923

A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma.

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Nowak, A K; Cook, A M; McDonnell, A M; Millward, M J; Creaney, J; Francis, R J; Hasani, A; Segal, A; Musk, A W; Turlach, B A; McCoy, M J; Robinson, B W S; Lake, R A

2015-12-01

Data from murine models suggest that CD40 activation may synergize with cytotoxic chemotherapy. We aimed to determine the maximum tolerated dose (MTD) and toxicity profile and to explore immunological biomarkers of the CD40-activating antibody CP-870,893 with cisplatin and pemetrexed in patients with malignant pleural mesothelioma (MPM). Eligible patients had confirmed MPM, ECOG performance status 0-1, and measurable disease. Patients received cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 and CP-870,893 on day 8 of a 21-day cycle for maximum 6 cycles with up to 6 subsequent cycles single-agent CP-870,893. Immune cell subset changes were examined weekly by flow cytometry. Fifteen patients were treated at three dose levels. The MTD of CP-870,893 was 0.15 mg/kg, and was exceeded at 0.2 mg/kg with one grade 4 splenic infarction and one grade 3 confusion and hyponatraemia. Cytokine release syndrome (CRS) occurred in most patients (80%) following CP-870,893. Haematological toxicities were consistent with cisplatin and pemetrexed chemotherapy. Six partial responses (40%) and 9 stable disease (53%) as best response were observed. The median overall survival was 16.5 months; the median progression-free survival was 6.3 months. Three patients survived beyond 30 months. CD19+ B cells decreased over 6 cycles of chemoimmunotherapy (P CP-870,893 with cisplatin and pemetrexed is safe and tolerable at 0.15 mg/kg, although most patients experience CRS. While objective response rates are similar to chemotherapy alone, three patients achieved long-term survival. ACTRN12609000294257. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Pemetrexed induced thymidylate synthase inhibition in non-small cell lung cancer patients: a pilot study with 3'-deoxy-3'-[¹⁸F]fluorothymidine positron emission tomography.

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Virginie Frings

Full Text Available OBJECTIVES: Pemetrexed is a thymidylate synthase (TS inhibitor and is effective in non-small cell lung cancer (NSCLC. 3'-deoxy-3'-[¹⁸F]fluorothymidine (¹⁸F-FLT, a proliferation marker, could potentially identify tumor specific TS-inhibition. The aim of this study was to investigate the effect of pemetrexed-induced TS-inhibition on ¹⁸F-FLT uptake 4 hours after pemetrexed administration in metastatic NSCLC patients. METHODS: Fourteen NSCLC patients underwent dynamic ¹⁸F-FLT positron emission tomography (PET scans at baseline and 4 hours after the first dose of pemetrexed. Volumes of interest were defined with a 41%, 50% and 70% threshold of the maximum pixel. Kinetic analysis and simplified measures were performed. At one, two, four and six hours after pemetrexed, plasma deoxyuridine was measured as systemic indicator of TS-inhibition. Tumor response measured with response evaluation criteria in solid tumors (RECIST, time to progression (TTP and overall survival (OS were determined. RESULTS: Eleven patients had evaluable ¹⁸F-FLT PET scans at baseline and 4 hours after pemetrexed. Two patients had increased ¹⁸F-FLT uptake of 35% and 31% after pemetrexed, whereas two other patients had decreased uptake of 31%. In the remaining seven patients ¹⁸F-FLT uptake did not change beyond test-retest borders. In all patients deoxyuridine levels raised after administration of pemetrexed, implicating pemetrexed-induced TS-inhibition. ¹⁸F-FLT uptake in bone marrow was significantly increased 4 hours after pemetrexed administration. Six weeks after the start of treatment 5 patients had partial response, 4 stable disease and 2 progressive disease. Median TTP was 4.2 months (range 3.0-7.4 months; median OS was 13.0 months (range 5.1-30.8 months. Changes in ¹⁸F-FLT uptake were not predictive for tumor response, TTP or OS. CONCLUSIONS: Measuring TS-inhibition in a clinical setting 4 hours after pemetrexed revealed a non-systematic change in

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

International Nuclear Information System (INIS)

Shen, Xinglei; DeNittis, Albert; Werner-Wasik, Maria; Axelrod, Rita; Gilman, Paul; Meyer, Thomas; Treat, Joseph; Curran, Walter J; Machtay, Mitchell

2011-01-01

This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m 2 . Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m 2 , but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m 2 ) q3 weeks × 2 -3 cycles. Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m 2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.

Carboplatin-pemetrexed in treatment of patients with recurrent/metastatic cancers of the head and neck; superior outcomes in oropharyngeal primaries.

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Binu eMalhotra

2015-01-01

Full Text Available Background – Platinum based therapy in combination with 5-fluorouracil with cetuximab has shown the best survival in pts with recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN. The purpose of this study is to evaluate the efficacy and tolerability of carboplatin, pemetrexed and to assess differential outcomes in patients with oropharyngeal primary and HPV related disease.Patients and Methods –The charts of consecutive patients with R/M SCCHN were reviewed. All patients receiving at least 1 cycle of the 2-drug regimen (pemetrexed 500 mg/m2, carboplatin area under the curve of 5 intravenously, were included for assessment of response, safety, toxicity and survival.Results - A total of 86 patients received this regimen between January 2008 and December 2012, of which, 63 were included in this analysis. Forty one percent (26 of the patients had cancers of the oropharynx, and of those, 50% had HPV positive disease, 32% (20 had cancers of the larynx and 24% (15 of the oral cavity. Median number of cycles administered was 4 (range 1-14 cycles with 50% of the patients receiving 4 or more cycles. Half the patients achieved stable disease as their best response, 8% (5 attained a partial response, 24% progressed on therapy and the remaining patients (12 could not have their response assessed.On the basis of Kaplan Meier analysis, median progression free survival (PFS was 5.1 months (95% CI 3.2, 6.2 and median overall survival (OS was 9.4 months (95% CI 4.3, 13.1. Among pts with oropharyngeal primary (n=26, median PFS was 6.4 months (95% CI 2.8, 7.9 and median OS was 16.6 months (95% CI 9.6, 19.5. Among HPV+ pts (n=13, median PFS was 7.0 months (95% CI 4.8, ne and median OS was 17.1 months (95% CI 11.2, 21.7. Conclusion: Combination carboplatin-pemetrexed is an effective and well tolerated treatment, associated with a median PFS of 5.1 months and a clinical benefit in at least 57% of the patients treated.

Noninvasive monitoring of the genetic evolution of EGFR-mutant non-small-cell lung cancer by analyzing circulating tumor DNA during combination chemotherapy with gefitinib and pemetrexed or S-1

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Nakahara Y

2016-08-01

Full Text Available Yoshiro Nakahara,1,2 Yusuke Takagi,1,3 Yukio Hosomi,1 Akiko Kagei,4 Tomohiro Yamamoto,4 Takeshi Sawada,5 Makiko Yomota,1 Yusuke Okuma,1 Shinichiro Mikura,1,6 Tatsuru Okamura1 1Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 2Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, 3Oncology Scientific Affairs, Merck Sharp & Dohme Corp, 4GeneticLab Co., Ltd., Sapporo, 5Department of Medical Oncology, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, 6Department of Respiratory Medicine, Fujieda Municipal General Hospital, Fujieda, Japan Background: Repetitive genotyping is useful to assess the genetic evolution of non-small-cell lung cancer (NSCLC during treatment, but the need for sampling by biopsy is a major obstacle. Digital polymerase chain reaction (PCR is a promising procedure for the detection of mutant alleles in plasma of cancer patients.Methods: This prospective study enrolled patients with NSCLC and known epidermal growth factor receptor (EGFR mutations and who had experienced disease progression during ongoing EGFR-tyrosine kinase inhibitor (TKI therapy. Eligible patients received daily gefitinib and either pemetrexed or S-1 every 3 weeks until disease progression or the development of unacceptable toxicity. Peripheral blood was collected before and after the combination therapy for digital PCR and hepatocyte growth factor measurement.Results: From May 2012 to January 2014, nine patients with a median age of 67 (range 52–80 years were enrolled. Patterns of disease progression during adjacent EGFR-TKI therapy were acquired resistance, observed in seven patients, and primary resistance, observed in two patients. Known EGFR mutations were detected in plasma samples of six (67% patients at study enrollment. Of these, T790M mutation was concurrently detected in three (50% patients

[PARAMOUNT trial: clinical meaning of continuous maintenance therapy in lung cancer].

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Gridelli, Cesare

2015-05-01

Non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer related deaths worldwide across both sex. Patients with Advanced -NSCLC (A-NSCLC) do not have curative treatment options, so the primary endpoint of every therapeutic decision aims to prolong survival, improving or maintain a good Quality of Life (QoL). Histology could represent a positive predictive factor for patients with Non squamous NSCLC (Nsq-NSCLC) respect to pemetrexed treatment. Pemetrexed is an antifolate that inhibits primarily thymidylate synthase (TS), together with dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. Pemetrexed in combination with cisplatin is approved in the first line setting and as monotherapy in the switch or continuous maintenance of Non Squamous A-NSCLC. Maintenance therapy is a widely used therapeutic option in other solid and hematologic malignancies, but in the A-NSCLC represent an innovative approach. The rationale in this new setting of patients is based on the evidence that patients who benefit from an initial induction therapy platinum based may benefit from maintenance therapy with the third generation agent dropping the platinum drug after four to six cycles. We can define two types of maintenance therapy: continuation maintenance and switch maintenance. Major results in prolonging Overall Survival (OS) was reported with the continuation maintenance strategy as in the PARAMOUNT trial.

Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

DEFF Research Database (Denmark)

Scagliotti, G.V.; Parikh, P.; Pawel, J. von

2008-01-01

, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/ gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P ... neutropenia (P = .002); and alopecia (P

Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV non-small cell lung cancer.

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Socinski, Mark A; Raju, Robert N; Stinchcombe, Thomas; Kocs, Darren M; Couch, Linda S; Barrera, David; Rousey, Steven R; Choksi, Janak K; Jotte, Robert; Patt, Debra A; Periman, Phillip O; Schlossberg, Howard R; Weissman, Charles H; Wang, Yunfei; Asmar, Lina; Pritchard, Sharon; Bromund, Jane; Peng, Guangbin; Treat, Joseph; Obasaju, Coleman K

2010-12-01

Enzastaurin is an oral serine/threonine kinase inhibitor that targets protein kinase C-beta (PKC-β) and the phosphatidylinositol-3-kinase/AKT pathway. This trial assessed pemetrexed-carboplatin ± enzastaurin to docetaxel-carboplatin in advanced non-small cell lung cancer. Patients with stage IIIB (with pleural effusion) or IV non-small cell lung cancer and performance status 0 or 1 were randomized to one of the three arms: (A) pemetrexed 500 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to 6 cycles with a loading dose of enzastaurin 1125 or 1200 mg followed by 500 mg daily until disease progression, (B) the same regimen of pemetrexed-carboplatin without enzastaurin, or (C) docetaxel 75 mg/m and carboplatin area under the curve 6 once every 3 weeks for up to six cycles. The primary end point was time to disease progression (TTP). Between March 2006 and May 2008, 218 patients were randomized. Median TTP was 4.6 months for pemetrexed-carboplatin-enzastaurin, 6.0 months for pemetrexed-carboplatin, and 4.1 months for docetaxel-carboplatin (differences not significant). Median survival was 7.2 months for pemetrexed-carboplatin-enzastaurin, 12.7 months for pemetrexed-carboplatin, and 9.2 months for docetaxel-carboplatin (log-rank p = 0.05). Compared with the other arms, docetaxel-carboplatin was associated with lower rates of grade 3 thrombocytopenia and anemia but a higher rate of grade 3 or 4 febrile neutropenia. There was no difference in TTP between the three arms, but survival was longer with pemetrexed-carboplatin compared with docetaxel-carboplatin. Enzastaurin did not add to the activity of pemetrexed-carboplatin.

Preliminary Safety, Pharmacokinetics, and Efficacy of Regorafenib, Cisplatin, and Pemetrexed in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancers.

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Hellmann, Matthew D; Sturm, Isrid; Trnkova, Zuzana Jirakova; Lettieri, John; Diefenbach, Konstanze; Rizvi, Naiyer A; Gettinger, Scott N

2015-11-01

Regorafenib is an oral multitargeted kinase inhibitor with potent antiangiogenic activity. In this phase I trial we evaluated the safety, pharmacokinetics, and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nonsquamous non-small-cell lung cancers (nsNSCLCs). Nine patients enrolled before premature termination of the study. Five of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range, 1.5-15.1 months). Regorafenib had acceptable tolerability and minor pharmacokinetic interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. The combination of bevacizumab, an antiangiogenesis agent, with cytotoxic chemotherapy improves survival in patients with advanced nonsquamous non-small-cell lung cancers (nsNSCLCs). Regorafenib is an oral multitargeted kinase inhibitor with potent antiangiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. In this phase I trial we evaluated the safety, pharmacokinetics (PK), and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Chemotherapy-naive patients with advanced nsNSCLCs were treated with regorafenib 60 mg/d continuously and cisplatin 75 mg/m(2) with pemetrexed 500 mg/m(2) once every 21 days for up to 6 cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Nine patients enrolled before premature termination of the study because of slow recruitment and a change in the development strategy of regorafenib by the study sponsor. Five patients experienced at least 1 treatment-related Grade 3 adverse event. No Grade 4 or 5 toxicity occurred. Five of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range, 1.5-15.1 months). Minor PK interactions between regorafenib and chemotherapy were observed. Regorafenib had acceptable

Randomized Phase II Study of Pemetrexed, Carboplatin, and Thoracic Radiation With or Without Cetuximab in Patients With Locally Advanced Unresectable Non–Small-Cell Lung Cancer: Cancer and Leukemia Group B Trial 30407

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Govindan, Ramaswamy; Bogart, Jeffrey; Stinchcombe, Thomas; Wang, Xiaofei; Hodgson, Lydia; Kratzke, Robert; Garst, Jennifer; Brotherton, Timothy; Vokes, Everett E.

2011-01-01

Purpose Cancer and Leukemia Group B conducted a randomized phase II trial to investigate two novel chemotherapy regimens in combination with concurrent thoracic radiation therapy (TRT). Patients and Methods Patients with unresectable stage III non–small-cell lung cancer (NSCLC) were randomly assigned to carboplatin (area under the curve, 5) and pemetrexed (500 mg/m2) every 21 days for four cycles and TRT (70 Gy; arm A) or the same treatment with cetuximab administered concurrent only with TRT (arm B). Patients in both arms received up to four cycles of pemetrexed as consolidation therapy. The primary end point was the 18-month overall survival (OS) rate; if the 18-month OS rate was ≥ 55%, the regimen(s) would be considered for further study. Results Of the 101 eligible patients enrolled (48 in arm A and 53 in arm B), 60% were male; the median age was 66 years (range, 32 to 81 years); 44% and 35% had adenocarcinoma and squamous carcinoma, respectively; and more patients enrolled onto arm A compared with arm B had a performance status of 0 (58% v 34%, respectively; P = .04). The 18-month OS rate was 58% (95% CI, 46% to 74%) in arm A and 54% (95% CI, 42% to 70%) in arm B. No significant difference in OS between patients with squamous and nonsquamous NSCLC was observed (P = .667). The toxicities observed were consistent with toxicities associated with concurrent chemoradiotherapy. Conclusion The combination of pemetrexed, carboplatin, and TRT met the prespecified criteria for further evaluation. This regimen should be studied further in patients with locally advanced unresectable nonsquamous NSCLC. PMID:21747084

Novel therapies for malignant pleural mesothelioma.

Science.gov (United States)

Scherpereel, Arnaud; Wallyn, Frederic; Albelda, Steven M; Munck, Camille

2018-03-01

Malignant pleural mesothelioma is a rare cancer that is typically associated with exposure to asbestos. Patients with malignant pleural mesothelioma have poor outcomes with suboptimal therapeutic options and currently no treatment is curative. The standard frontline treatment, cisplatin plus pemetrexed chemotherapy, has only short and insufficient efficacy, and no validated treatment beyond first-line therapy is available. New therapeutic strategies are therefore needed. The addition of bevacizumab (an anti-VEGF antibody) combined with cisplatin plus pemetrexed has shown some promise. However, immunotherapy, especially immune checkpoint inhibitors, has generated a lot of excitement because of data suggesting the potential value of immune checkpoint inhibitors for patients who have failed chemotherapy. In this Review, we describe immune checkpoint inhibitors, other immunotherapies, targeted therapies, or combinations of novel drugs being investigated in malignant pleural mesothelioma, as well as the issues surrounding the selection of the best candidates for these treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Case of Posterior Reversible Encephalopathy Syndrome Induced by Cisplatin/Pemetrexed Chemotherapy for Lung Cancer

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Masashi Ishihara

2017-03-01

Full Text Available This report presents the case of a 60-year-old woman who was diagnosed with stage IV lung adenocarcinoma with asymptomatic brain metastases and commenced chemotherapy with cisplatin/pemetrexed (CDDP/Pem. She experienced tonic-clonic convulsions on day 9 of the first cycle, which were accompanied by increased blood pressure (173/69 mm Hg and headache. Therefore, brain MRI was performed to check for stroke or progression of brain metastatic foci. T2-weighted, FLAIR, and ADC map images showed high-intensity areas in the subcortical region of the bilateral parieto-occipital lobes, leading to a diagnosis of posterior reversible encephalopathy syndrome (PRES. The symptoms improved after treatment with antihypertensive and antiepileptic drugs. Clinicians should keep it in mind that central nervous system symptoms during anticancer therapy containing Pem may indicate possible PRES.

Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma

International Nuclear Information System (INIS)

Goricar, Katja; Kovac, Viljem; Dolzan, Vita

2014-01-01

A combination of pemetrexed and cisplatin has been shown to improve the outcome in patients with malignant pleural mesothelioma (MPM), however, there is a great heterogeneity in treatment response among patients. The aim of our study was to evaluate the influence of polymorphisms in folate pathway and transporter genes on pemetrexed treatment outcome in Slovenian patients with MPM. MPM patients treated with pemetrexed in the course of a prospective randomized clinical trial were genotyped for nineteen polymorphisms in five genes of folate pathway and six transporter genes. Logistic regression was used to assess the influence of polymorphisms on treatment efficacy and toxicity, while Cox regression was used to determine their influence on progression-free and overall survival. Patients with at least one polymorphic MTHFD1 rs2236225 allele had a significantly lower response rate (p = 0.005; odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.03−0.54) and shorter progression-free survival (p = 0.032; hazard ratio [HR] = 3.10; 95% CI = 1.10−8.74) than non-carriers. Polymorphisms in transporter genes did not influence survival; however, several were associated with toxicity. Liver toxicity was significantly lower in carriers of polymorphic ABCC2 rs2273697 (p = 0.028; OR = 0.23; 95% CI = 0.06−0.85), SLCO1B1 rs4149056 (p = 0.028; OR = 0.23; 95% CI = 0.06−0.85) and rs11045879 (p = 0.014; OR = 0.18; 95% CI = 0.05−0.71) alleles compared to non-carriers, as well as in patients with SLCO1B1 GCAC haplotype (p = 0.048; OR = 0.17; 95% CI = 0.03−0.98). Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p = 0.004; OR = 10.67; 95% CI = 2.15−52.85) and ABCC2 CAG haplotype (p = 0.006; OR = 5.67; 95% CI = 1.64−19.66). MTHFD1 polymorphism affected treatment response and survival, while polymorphisms in ABCC2 and SLCO1B1 transporter genes influenced the risk for toxicity. These polymorphisms could serve as potential

Combination chemotherapy with intermittent erlotinib and pemetrexed for pretreated patients with advanced non-small cell lung cancer: a phase I dose-finding study

International Nuclear Information System (INIS)

Minami, Seigo; Tachibana, Isao; Komuta, Kiyoshi; Kawase, Ichiro; Kijima, Takashi; Takahashi, Ryo; Kida, Hiroshi; Nakatani, Takeshi; Hamaguchi, Masanari; Takeuchi, Yoshiko; Nagatomo, Izumi; Yamamoto, Suguru

2012-01-01

Erlotinib and pemetrexed have been approved for the second-line treatment of non-small cell lung cancer (NSCLC). These two agents have different mechanisms of action. Combined treatment with erlotinib and pemetrexed could potentially augment the antitumor activity of either agent alone. In the present study, we investigated the safety profile of combined administration of the two agents in pretreated NSCLC patients. A phase I dose-finding study (Trial registration: UMIN000002900) was performed in patients with stage III/IV nonsquamous NSCLC whose disease had progressed on or after receiving first-line chemotherapy. Patients received 500 mg/m 2 of pemetrexed intravenously every 21 days and erlotinib (100 mg at Level 1 and 150 mg at Level 2) orally on days 2–16. Twelve patients, nine males and three females, were recruited. Patient characteristics included a median age of 66 years (range, 48–78 years), stage IV disease (nine cases), adenocarcinoma (seven cases) and activating mutation-positives in the epidermal growth factor receptor gene (two cases). Treatment was well-tolerated, and the recommended dose of erlotinib was fixed at 150 mg. Dose-limiting toxicities were experienced in three patients and included: grade 3 elevation of serum alanine aminotransferase, repetitive grade 4 neutropenia that required reduction of the second dose of pemetrexed and grade 3 diarrhea. No patient experienced drug-induced interstitial lung disease. Three patients achieved a partial response and stable disease was maintained in five patients. Combination chemotherapy of intermittent erlotinib with pemetrexed was well-tolerated, with promising efficacy against pretreated advanced nonsquamous NSCLC

An Open-Label, Multicenter, Randomized, Phase II Study of Pazopanib in Combination with Pemetrexed in First-Line Treatment of Patients with Advanced-Stage Non-Small-Cell Lung Cancer

DEFF Research Database (Denmark)

Scagliotti, Giorgio V; Felip, Enriqueta; Besse, Benjamin

2013-01-01

This randomized open-label phase II study evaluated the efficacy, safety, and tolerability of pazopanib in combination with pemetrexed compared with the standard cisplatin/pemetrexed doublet in patients with previously untreated, advanced, nonsquamous non-small-cell lung cancer....

Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

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Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

2007-07-01

Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

Preliminary safety, pharmacokinetics, and efficacy of regorafenib, cisplatin, and pemetrexed in patients with advanced non-squamous non-small cell lung cancers

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Hellmann, Matthew D; Sturm, Isrid; Trnkova, Zuzana Jirakova; Lettieri, John; Diefenbach, Konstanze; Rizvi, Naiyer A.; Gettinger, Scott N.

2016-01-01

Structured Abstract Purpose The addition of bevacizumab, an anti-angiogenesis agent, to cytotoxic chemotherapy improves survival in patients with advanced non-squamous non-small cell lung cancers (nsNSCLCs). Regorafenib is an oral multi-targeted kinase inhibitor with potent anti-angiogenic activity that is approved for patients with advanced colorectal cancer and gastrointestinal stromal tumors. This phase I trial evaluated the safety, pharmacokinetics, and efficacy of regorafenib with cisplatin and pemetrexed for patients with advanced nsNSCLCs. Methods Chemotherapy-naïve patients with advanced nsNSCLCs were treated with regorafenib 60mg/day continuously and cisplatin 75mg/m2 plus pemetrexed 500mg/m2 once every three weeks for up to six cycles. Thereafter, regorafenib with or without pemetrexed could be continued as maintenance. Results Nine patients enrolled prior to premature termination of the study due to slow recruitment and a change in the development strategy of regorafenib by the study sponsor, partially due to slow enrollment. Five patients experienced at least one treatment-related Grade 3 adverse event. No grade 4–5 toxicity occurred. 5 of 9 (56%) patients had a partial response and the median progression-free survival was 7 months (range 1.5–15.1). Minor pharmacokinetic (PK) interactions between regorafenib and chemotherapy were observed. Conclusions Regorafenib had acceptable tolerability and minor PK interactions in combination with standard doses of cisplatin and pemetrexed in patients with advanced nsNSCLCs. Encouraging activity was appreciated in chemotherapy-naïve patients with advanced nsNSCLCs. However, the small number of patients treated limits conclusions that can be drawn from these results. PMID:26003007

Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma

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Songliang ZHANG

2015-06-01

Full Text Available Background and objective Bevacizumab has showed its efficacy in advanced non-squamous lung cancer. The aim of this study is to assess the safety of bevacizumab plus pemetrexed and carboplatin neoadjuvant chemotherapy in patients with lung adenocarcinoma. Methods 25 patients with IIIa lung adenocarcinoma undergoing lobectemy or pneumonectomy with mediastinal lymphadenectomy after induction bevacizumab (Bev plus pemetrexed/carboplatin (PC were selected. Toxicity of chemotherapy and postoperative complications were analyzed. Results Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients, neutropenia (3 patients, hypertension (1 patient. The adverse events thought to be related to bevacizumab included epistaxis in 2 patients (grade 1: 1; grade 2: 1 and hypertension in 3 patients (grade 1: 2; grade 3: 1. Postoperative complications included pneumonia in 2 patients, bronchial stump insufficiency in 1 case, atelectasis in 2 cases, and arrhythmia in 1 case. Hemorrhage events, thromboembolic events and wound-healing problems were not observed in the perioperative period. Conclusion The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma.

Icotinib antagonizes ABCG2-mediated multidrug resistance, but not the pemetrexed resistance mediated by thymidylate synthase and ABCG2.

Science.gov (United States)

Wang, De-Shen; Patel, Atish; Shukla, Suneet; Zhang, Yun-Kai; Wang, Yi-Jun; Kathawala, Rishil J; Robey, Robert W; Zhang, Li; Yang, Dong-Hua; Talele, Tanaji T; Bates, Susan E; Ambudkar, Suresh V; Xu, Rui-Hua; Chen, Zhe-Sheng

2014-06-30

ABCG2 is a potential biomarker causing multidrug resistance (MDR) in Non-Small Cell Lung Cancer (NSCLC). We conducted this study to investigate whether Icotinib, a small-molecule inhibitor of EGFR tyrosine kinase, could interact with ABCG2 transporter in NSCLC. Our results showed that Icotinib reversed ABCG2-mediated MDR by antagonizing the drug efflux function of ABCG2. Icotinib stimulated the ATPase activity in a concentration-dependent manner and inhibited the photolabeling of ABCG2 with [125I]-Iodoarylazidoprazosin, demonstrating that it interacts at the drug-binding pocket. Homology modeling predicted the binding conformation of Icotinib at Asn629 centroid-based grid of ABCG2. However, Icotinib at reversal concentration did not affect the expression levels of AKT and ABCG2. Furthermore, a combination of Icotinib and topotecan exhibited significant synergistic anticancer activity against NCI-H460/MX20 tumor xenografts. However, the inhibition of transport activity of ABCG2 was insufficient to overcome pemetrexed resistance in NCI-H460/MX20 cells, which was due to the co-upregulated thymidylate synthase (TS) and ABCG2 expression. This is the first report to show that the up-regulation of TS in ABCG2-overexpressing cell line NCI-H460/MX20 may play a role of resistance to pemetrexate. Our findings suggested different possible strategies of overcoming the resistance of topotecan and pemetrexed in the NSCLC patients.

Novel drug-resistance mechanisms of pemetrexed-treated non-small cell lung cancer.

Science.gov (United States)

Tanino, Ryosuke; Tsubata, Yukari; Harashima, Nanae; Harada, Mamoru; Isobe, Takeshi

2018-03-30

Pemetrexed (PEM) improves the overall survival of patients with advanced non-small cell lung cancer (NSCLC) when administered as maintenance therapy. However, PEM resistance often appears during the therapy. Although thymidylate synthase is known to be responsible for PEM resistance, no other mechanisms have been investigated in detail. In this study, we explored new drug resistance mechanisms of PEM-treated NSCLC using two combinations of parental and PEM-resistant NSCLC cell lines from PC-9 and A549. PEM increased the apoptosis cells in parental PC-9 and the senescent cells in parental A549. However, such changes were not observed in the respective PEM-resistant cell lines. Quantitative RT-PCR analysis revealed that, besides an increased gene expression of thymidylate synthase in PEM-resistant PC-9 cells, the solute carrier family 19 member1 ( SLC19A1) gene expression was markedly decreased in PEM-resistant A549 cells. The siRNA-mediated knockdown of SLC19A1 endowed the parental cell lines with PEM resistance. Conversely, PEM-resistant PC-9 cells carrying an epidermal growth factor receptor (EGFR) mutation acquired resistance to a tyrosine kinase inhibitor erlotinib. Although erlotinib can inhibit the phosphorylation of EGFR and Erk, it is unable to suppress the phosphorylation of Akt in PEM-resistant PC-9 cells. Additionally, PEM-resistant PC-9 cells were less sensitive to the PI3K inhibitor LY294002 than parental PC-9 cells. These results indicate that SLC19A1 negatively regulates PEM resistance in NSCLC, and that EGFR-tyrosine-kinase-inhibitor resistance was acquired with PEM resistance through Akt activation in NSCLC harboring EGFR mutations.

A Randomized, Controlled, Multicenter Clinical Trial Comparing Pemetrexed/Cisplatin and Gemcitabine/Cisplatin as First-line Treatment for Advanced Nonsquamous Non-small Cell Lung Cancer

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Yan HUANG

2012-10-01

Full Text Available Background and objective Platinum-based doublet chemotherapy is still the standard first-line treatment for non-small cell lung cancer (NSCLC. Previous studies have demonstrated that pemetrexed combined with platinum had promising efficacy and safety profile in NSCLC, especially in patients with nonsquamous NSCLC. This trial was conducted to evaluate the efficacy and safety of pemetrexed made in China as first-line treatment. Methods The present study was a randomized, controlled, multicenter clinical trial. Patients were randomly assigned (1:1 to receive cisplatin plus pemetrexed chemotherapy (PC group or gemcitabine plus cisplatin (GC group every 3 weeks. The primary end point was progression free survival (PFS and the secondary end points included 1 year survival rate, objective response rate (ORR, survival without grade 3/4 toxicity (SWT3/4 and safety profile. Results A total of 288 patients from 20 institutions across China were enrolled into the study. Based on the Full Analyses Set (FAS, the PFS was 168 days (5.6 months vs 140 days (4.7 months (P=0.16, one year survival rate was 50.0% vs 54.9% (P=0.47, ORR was 24.4% vs 14.2% (P=0.06 in the PC group and the GC group, respectively; Survival without grade 3/4 toxicity was 11.3 months in GC group vs 8.1 months in PC group (P=0.23. In terms of the safety, side effects were less observed on the PC group (81.95% vs 93.75%, P=0.003. The main side effects included leukopenia, neutropenia, emesis, anemia, thrombopenia. Conclusion The both regimens have similar efficacy as the treatment for advanced nonsquamous NSCLC, but pemetrexed plus cisplatin regimen has better safety profile and seems to have longer PFS, which makes it a new option as the first line setting.

Sequentially administrated of pemetrexed with icotinib/erlotinib in lung adenocarcinoma cell lines in vitro

OpenAIRE

Feng, Xiuli; Zhang, Yan; Li, Tao; Li, Yu

2017-01-01

Combination of chemotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) had been proved to be a potent anti-drug for the treatment of tumors. However, survival time was not extended for the patients with lung adenocarcinoma (AdC) compared with first-line chemotherapy. In the present study, we attempt to assess the optimal schedule of the combined administration of pemetrexed and icotinib/erlotinib in AdC cell lines. Human lung AdC cell lines with wild-type (A54...

Second-line Treatment of Stage III/IV Non-Small-Cell Lung Cancer (NSCLC with pemetrexed in routine clinical practice: Evaluation of performance status and health-related quality of life

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Schuette Wolfgang

2012-01-01

Full Text Available Abstract Background Second-line treatment of advanced non-small-cell lung cancer (NSCLC improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS and health-related quality of life (HR-QoL during second-line pemetrexed treatment in routine clinical practice. Methods Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI of ≥ 10% (absolute or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response". HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D. Factors potentially associated with KI benefit response were evaluated using logistic regression models. Results Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%, 471 (90.4% completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2% achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%. Conclusions In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years, physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients. Trial registration Registered on ClinicalTrials.gov (NCT00540241 on October 4, 2007

65Plus: open-label study of bevacizumab in combination with pemetrexed or pemetrexed/carboplatin as first-line treatment of patients with advanced or recurrent nonsquamous non-small-cell lung cancer

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Schuette W

2017-11-01

Full Text Available Wolfgang Schuette,1 Claus-Peter Schneider,2,3 Walburga Engel-Riedel,4 Christian Schumann,5,6 Martin Kohlhaeufl,7 Monika Heidi Ursel Serke,8 Gert Hoeffken,9 Cornelius Kortsik,10 Martin Reck11 1Department of Internal Medicine II, Hospital Martha-Maria Halle-Doelau, Halle, 2Department of Pneumonology, Central Hospital, Bad Berka, 3Department of Internal Medicine, DRK Manniske Hospital, Bad Frankenhausen, 4Cologne Clinics, Merheim Lung Hospital, Cologne, 5Pneumonology, Department of Internal Medicine II, University Hospital Ulm, 6Clinic for Pneumology, Thoracic Oncology, Sleep, and Respiratory Critical Care, Kempten-Oberallgäu, 7Center of Pneumonology and Chest Surgery, Hospital Schillerhoehe, Gerlingen, 8Pneumonology, Lung Clinics, Hemer, 9Center of Pneumonology, Chest and Vascular Surgery, Specialty Hospital Coswig, Coswig, 10Department of Pneumonology, Catholic Hospital, Mainz, 11Department of Thoracic Oncology, Lung Clinic, Grosshansdorf, Germany Background: The aim of the study was to investigate in terms of noninferiority the efficacy and safety of a monochemotherapy regimen of pemetrexed plus bevacizumab (BevPem versus carboplatin/pemetrexed plus bevacizumab (BevCPem in elderly patients as first-line treatment for advanced metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC.Materials and methods: 65Plus was a Phase III, randomized, open-label study. In total, 253 patients received BevPem (n=119 or BevCPem (n=134. The primary outcome measure was progression-free survival. Secondary end points were overall survival, tumor response, and safety outcomes. Evaluations were performed for the whole study population and stratified according to Eastern Cooperative Oncology Group (ECOG performance status (PS.Results: Noninferiority of BevPem in comparison to BevCPem could not be demonstrated for the overall population (P=0.7864. Significant superiority of the combined treatment BevCPem was seen in patients of ECOG PS 0–1 (median

Radiation-hygienic estimation of interstitial gamma therapy conducted according to principle of subsequent introduction of radioactive sources

International Nuclear Information System (INIS)

Zamyatin, O.A.; Golikov, V.Ya.; Korenkov, I.P.; Ter-Kazar'yan, N.S.; Mindlin, G.M.

1978-01-01

A comparative study of two radiation-hygienic methods of interstitial gamma-therapy: with subsequent introduction of radioactive needles of a standard type; with subsequent manual introduction of 60 Co sources have been carried out. Chronometry-dosimetric methods of investigation and the methods of individual dosimetry underlie the studies. The obtained data showed, that doses of irradiation to which medical personnel is subjected during the use of the method of subsequent manual introduction of the active sources are 3-4 times lower, than those during the introduction of standard radioactive needles with a higher quality of the procedure performance, ensuring a good therapeutic effect. All this makes it possible to consider interstitial gamma-therapy with the use of the principle of subsequent introduction of the source to be a more perspective method than interstitial gamma-therapy with the use standard radioactive needless 60 Co

Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

International Nuclear Information System (INIS)

Russo, Francesca; Bearz, Alessandra; Pampaloni, Gianni; The investigators of the Italian Pemetrexed monotherapy of NSCLC group

2008-01-01

The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC. Overall, 95 patients received pemetrexed 500 mg/m 2 i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria. Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated) reported at least one adverse event: 34 (35.8%) had grade 3 as worst grade and only 5 (5.2%) had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4%) and leukopenia (6.3 %) were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%), fatigue (3.2%) and dyspnea (3.2%) were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade) were pyrexia (11.6%), vomiting, nausea, diarrhea and asthenia (9.5%) and fatigue (8.4%). Tumor Response Rate (CR/PR) in treated patients was 9.2%. The survival at 4.5 months (median follow-up) was 79% and the median PFS was 3.1 months. Twenty patients (21.1%) died mainly because of disease progression. Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities

Comparative study analyzing survival and safety of bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed in chemotherapy-naïve patients with advanced non-squamous bronchogenic carcinoma not harboring EGFR mutation

Directory of Open Access Journals (Sweden)

Abdel Kader Y

2013-07-01

Full Text Available Yasser Abdel Kader,1 Thierry Le Chevalier,2 Tamer El-Nahas,1 Amr Sakr11Department of Clinical Oncology, Cairo University, Cairo, Egypt; 2Department of Medical Oncology, Institut Gustave Roussy, Villejuif, Paris, FrancePurpose: The majority of Egyptian patients with lung cancer present at a late stage of the disease. Bevacizumab/carboplatin/paclitaxel, as well as cisplatin plus pemetrexed, are both standard regimens for advanced non-squamous bronchogenic cancer. This study compares both regimens, in terms of efficacy and toxicity profile, in Egyptian patients.Patients and methods: This is a randomized Phase II study comparing toxicity profile and survival in 41 chemotherapy-naïve patients with stage IIIB or IV non-squamous NSCLC, with an ECOG performance status of 0 to 2. The epidermal growth factor receptor (EGFR mutation detection was performed prior to treatment of all patients. Patients in the first group received: bevacizumab 7.5 mg/m2 on Day 1 and Day 15; carboplatin area under the curve-5 on Day 1; and paclitaxel 60 mg/m2 on Day 1, Day 8, and Day 15 every 4 weeks. In the second group, patients received cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 every 3 weeks.Results: The combination of bevacizumab/carboplatin/paclitaxel demonstrated higher Grade III–IV toxicity than cisplatin/pemetrexed regarding sensory/motor neuropathy (P = 0.06, DVT (P = 0.23, proteinuria (P = 0.23, and hypertension (P = 0.11, as well as Grade II alopecia (P = 0.001; however, no significant difference in toxicities between both arms was recorded regarding nausea and vomiting (P = 0.66, hematological toxicity, febrile neutropenia (P = 1 and fatigue (P = 0.66. Progression-free survival was similar for both treatment arms with a median of 6 months (P = 0.978. Overall median survival was comparable in both arms, 16.07 months versus 16.01 months (P = 0.89.Conclusion: Bevacizumab/carboplatin/paclitaxel and cisplatin/pemetrexed provided meaningful and comparable efficacy

Combined treatment with pemetrexed and vinflunine in patients with metastatic urothelial cell carcinoma after prior platinum-containing chemotherapy - results of an exploratory phase I study

DEFF Research Database (Denmark)

Pappot, H; von der Maase, H; Ullén, A

2017-01-01

experienced grade 4 thrombocytopenia and a second demonstrated hepatobiliary toxicity grade 3 with an increase in alanine aminotransaminase. Most common grade 3 and 4 adverse events were anemia, thrombocytopenia and neutropenia. Three out of four patients received 3 cycles of pemetrexed and vinflunine, all...

A new ultrafast and high-throughput mass spectrometric approach for the therapeutic drug monitoring of the multi-targeted anti-folate pemetrexed in plasma from lung cancer patients

NARCIS (Netherlands)

R.J.W. Meesters (Roland); R. Cornelissen (Robin); R.J. van Klaveren (Rob); R. de Jonge (Robert); E. den Boer (Ethan); J. Lindemans (Jan); T.M. Luider (Theo)

2010-01-01

textabstractAn analytical assay has been developed and validated for ultrafast and high-throughput mass spectrometric determination of pemetrexed concentrations in plasma using matrix assisted laser desorption/ionization-triple quadrupole-tandem mass spectrometry. Patient plasma samples spiked with

Effect of Pemetrexed combined with cis-platinum chemotherapy on matrix metalloproteinase VEGF, NK cells and immune function in patients with non-squamous non-small cell lung cancer

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Feng Wen

2017-07-01

Full Text Available Objective: To explore effect of Pemetrexed combined with cis-platinum chemotherapy on matrix metalloproteinase (MMPs, vascular esandothelial growth factor (VEGF, NK cells and immune function in patients with non-squamous non-small cell lung cancer. Method: A total of 86 cases of non-squamous non-small cell lung cancer patients were divided into control group (n=44 and observation group (n=42, control group was given docetaxel combined cisplatinum chemotherapy, pemetrexed combined cis-platinum chemotherapy, was applied for observation group. Compared MMP-2, MMP-9, VEGF, NK cells and immune function level before and after treatment in both groups. Results: MMP-2, MMP-9, VEGF, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+ level in both groups before treatment was no significant difference. After treatment, MMP-2, MMP-9, VEGF, CD8+level in both groups was significant lower than before treatment intra-group, and observation was lower than control group, there was significant difference. After treatment, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+ level in both groups was increased dramatically than before treatment of intra-group, moreover, NK cells, CD3+, CD4+, CD8+, CD4+/CD8+level in observation group after treatment was obvious higher than in control group after treatment, there was significant difference. Conclusion: Pemetrexed combined with cis-platinum chemotherapy for non-squamous non-small cell lung cancer could effectively decrease serum MMPs, VEGF level and increase NK cell level, regulate immune function, with definite clinical significance.

An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer

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A. Araújo

2008-11-01

Full Text Available Aim: Evaluate costs and benefits of erlotinib as 2nd or 3rd line treatment of advanced or metastatic nonsmall cell lung cancer (NSCLC versus docetaxel, pemetrexed and best supportive care. Materials and methods: Cost-minimisation and cost-utility analysis were performed. Time horizon of two years. Portuguese National Health System (NHS perspective was applied. Survival and time to progression were obtained from three clinical trials. Base-case analysis: 2nd or 3rd line patients with advanced or metastatic NSCLC. Quality Adjusted Life Years (QALYs were obtained from a UK study. Resource consumption was estimated by a Portuguese panel of experts. Costs were calculated according to official Portuguese databases (updated to 2008. Only direct health costs were applied. Annual discount rate: 5%. Sensitivity analysis included different subpopulations, a three year time horizon and a probabilistic analysis. Results: The cost per patient was lower with erlotinib (€26 478 than docetaxel (€29 262 or pemetrexed (€32 762 and higher than best supportive care (€16 112. QALYs per patient were higher with erlotinib (0.250 than docetaxel (0.225, pemetrexed (0.241 or best supportive care (0.186. Erlotinib was dominant in the cost-utility analysis, with a lower cost and a higher efficacy than docetaxel and pemetrexed. The sensitivity analysis confirmed the robustness of the base-case analysis results. Conclusions: The use of erlotinib instead of docetaxel or pemetrexed could contribute to annual savings for the NHS (substitution rates: 5%–65% ranging from €135 046-€1 755 602 (docetaxel replacement and €291 801-€3 793 409 (pemetrexed replacement, with a gain in terms of QALYs. Resumo: Objectivo: Avaliar o custo-efectividade de erlotinib na segunda ou terceira linha do tratamento do cancro do pulmão de não pequenas células (CPNPC avançado ou metastizado versus docetaxel, pemetrexedo ou tratamento de suporte

Radioiodine therapy and subsequent pregnancy

International Nuclear Information System (INIS)

Brandao, Carmen Dolores G.; Miranda, Angelica E.; Corres, Nilson Duarte; Sieiro Neto, Lino; Corbo, Rossana; Vaisman, Mario

2007-01-01

Objectives: To evaluate abortion and fetal congenital anomaly rates in women previously submitted to radioiodine therapy for differentiated thyroid carcinoma. Study design: A case-control study of 108 pregnant women, 48 cases whose pregnancies were evaluated after they had undergone radioiodine therapy for differentiated thyroid carcinoma, and the control group consisted of 60 healthy pregnant women. Results: Of a total of 66 pregnancies, 14 conceived within the first year, 51 one or more years after the last administration of 131 I, the medical record of one patient was not available. The interval between the last radioiodine therapy administration and conception ranged from 1 month to 10 years. There were a total of 4 miscarriages, 2 of them for unknown reasons. There was one case of congenital anomaly and two preterms birth. Nine women presented the following pregnancy events: placental insufficiency, hypertensive crisis, placental detachment, risk of miscarriage, preterm labour and four miscarriages. No statistical difference was observed between the studied and control groups. Conclusion: Radioiodine was followed by no significant increase in untoward effects in neither the pregnancy nor the offspring. (author)

Radioimmunotherapy of indolent non-Hodgkin's lymphoma with Yttrium-90 labeled anti-CD20 monoclonal antibody therapy does not preclude subsequent chemotherapy or autologous hematologic stem cell transplantation therapy in most patients

International Nuclear Information System (INIS)

Wiseman, G.A.; Witzig, T.E.; Ansell, S.M.; Ristow, K.M.

2002-01-01

Introduction: Yttrium-90 (Y-90) labeled anti-CD20 monoclonal antibody (ibritumomab tiuxetan or Zevalin TM ) is a novel therapy for patients with relapsed CD20+ B-cell non-Hodgkin's lymphoma (NHL). Patients treated with Zevalin radioimmunotherapy (RIT) are limited from higher doses due to transient and reversible platelet and neutrophil suppression. Patients with indolent NHL who relapse or are refractory to chemotherapy have a 70-80% overall response rate and a 20-30% complete response rate when treated with Zevalin RIT. Therefore additional treatment is required in a minority of patients shortly after Zevalin therapy and in many others at relapse. Relapsed patients are generally treated with chemotherapy alone or high dose chemotherapy followed by autologous transplantation. We wanted to evaluate the ability of patients to tolerate subsequent therapy given at relapse following Zevalin RIT. Methods: We had 58 patients who relapsed after receiving Zevalin RIT and later received additional therapy. The clinical records and lab results were reviewed and compared with a matched control group of patients treated prior to Zevalin availability who received chemotherapy without prior Zevalin RIT. Results: The toxicity in 58 patients treated with Zevalin RIT and subsequent therapy was not significantly different from the control group who did not receive Zevalin RIT. Patients had a median of two subsequent therapies (range, 1-7) after Zevalin. Twenty eight percent required blood cell growth factor support with subsequent chemotherapy and 2 patients required reductions from the standard chemotherapy doses due to prolonged myelosuppression. Eight patients subsequently had successful autologous hematologic stem cell transplant with cells collected after Zevalin. Thirteen of the 58 patients (28%) treated with standard dose chemotherapy were hospitalized for neutropenic fever or thrombocytopenia. Conclusions: Chemotherapy or high dose chemotherapy with autologous transplantation

[Safety and effectiveness of pemetrexed in patients with non-small cell lung cancer in Japan - analysis of post-marketing surveillance].

Science.gov (United States)

Okubo, Sumiko; Kobayashi, Noriko; Taketsuna, Masanori; Kaneko, Naoya; Enatsu, Sotaro; Nishiuma, Shinichi

2014-04-01

The safety and effectiveness of pemetrexed(PEM)in patients with non-small cell lung cancer(NSCLC)were reviewed using data from post-marketing surveillance. Among 699 patients registered from June 2009 to May 2010, 683 patients were analyzed(343, first-line therapy: 340, second-line therapy or beyond). Patient backgrounds were as follows: median age=65 years(16.1%B75 years old); 64.7% male; 91.9% performance status 0-1; 83.2% Stage IV; 99.0% non-squamous cell cancer. Also, 86% of the first-line and 20% of the second-line cohort were receiving a concomitant anti-cancer drug(mostly platinum agents). The incidence rate of adverse drug reactions(ADR)was 76.7%, including serious cases(18.0%). The most common ADRs were decreased white blood cell count(26.8%), decreased neutrophil count(25.3%), anemia(19.2%), decreased platelet count(17.0%), and nausea(23.0%). The incidence of interstitial lung disease, which is a concern during chemotherapy, was 2.6%. Peripheral neuropathy and alopecia, events influencing a patient's quality of life, were less than 1%. The estimated median survival time was 23.2 months[95%CI: 19.8 months-not calculable]in the first-line cohort, and 11.8 months[95% CI: 10.5-13.7 months]in the B second-line cohort. The surveillance results showed no apparent difference in total ADRs in this current study compared to the safety profile established in clinical trials previously conducted in Japan and overseas. These results demonstrate the safety and effectiveness of PEM treatment for NSCLC patients in daily clinical settings.

Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma

International Nuclear Information System (INIS)

Federico, Rea; Matteo, Ceccarelli; Gbenga, Kazeem; Paolo, Marchi; Francesco, Facciolo; Adolfo, Favaretto; Giuseppe, Marulli; Lorenzo, Spaggiari; Martino, DePas Tommaso; Anna, Ceribelli; Adriano, Paccagnella; Gino, Crivellari; Francesca, Russo

2013-01-01

Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results. Phase II, open-label study of the combination of chemotherapy (pemetrexed 500 mg/m 2 +cisplatin 75 mg/m 2 IV every 21 days × 3 cycles), followed by surgery (en-bloc extrapleural pneumonectomy, 3–8 weeks after chemotherapy) and hemithoracic radiation (total radiation beam 54 Gy, received 4–8 weeks post-surgery). The primary endpoint was event-free survival, defined as the time from enrollment to time of first observation of disease progression, death due to any cause, or early treatment discontinuation. Fifty-four treatment-naïve patients with T1-3 N0-2 malignant pleural mesothelioma were enrolled, 52 (96.3%) completed chemotherapy, 45 (83.3%) underwent surgery, 22 (40.7%) completed the whole treatment including 90-day post-radiation follow-up. The median event-free survival was 6.9 months (95%CI: 5.0-10.5), median overall survival was 15.5 months (95%CI 11.0-NA) while median time-to-tumor response was 4.8 months (95%CI: 2.5-8.0). Eighteen (33.3%) and 13 (24.1%) patients were still event-free after 1 and 2 years, respectively. The most common treatment-emergent adverse events were nausea (63.0%), anemia (51.9%) and hypertension (42.6%). Following two cardiopulmonary radiation-related deaths the protocol was amended (21 [38.9%] patients were already enrolled in the study): the total radiation beam was reduced from 54 Gy to 50.4 Gy and a more accurate selection of patients was recommended. The combination of pemetrexed plus cisplatin followed by surgery and hemithoracic radiation is feasible and has a manageable toxicity profile in carefully selected patients. It may be worthy of further investigation. Clinicaltrial.com registrationID #NCT00087698

Malignant pleural mesothelioma in a child

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Jed Brendan Scharf

2015-10-01

Full Text Available Malignant pleural mesothelioma (MPM is an aggressive malignancy that occurs extremely rarely in the pediatric population. It carries a dismal prognosis. Adult studies are often used to guide therapy in the pediatric population, as a limited number of case reports form the body of pediatric literature. Herein, we document the course and treatment of an 8-year old male diagnosed with MPM. The diagnosis came after he presented to his family physician with dyspnea and was found to have a large right-sided chest mass on subsequent imaging. Through an initial right pneumonectomy and subsequent chest wall excision, followed by chemotherapy with Pemetrexed and Cisplatin he remains virtually disease free today, almost 2 years following surgery.

Gene therapy, early promises, subsequent problems, and recent breakthroughs.

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Razi Soofiyani, Saeideh; Baradaran, Behzad; Lotfipour, Farzaneh; Kazemi, Tohid; Mohammadnejad, Leila

2013-01-01

Gene therapy is one of the most attractive fields in medicine. The concept of gene delivery to tissues for clinical applications has been discussed around half a century, but scientist's ability to manipulate genetic material via recombinant DNA technology made this purpose to reality. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. While gene therapy initially conceived as a way to treat life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, to date gene therapy is considered for many non-life-threatening conditions including those adversely influence on a patient's quality of life. Gene therapy has made significant progress, including tangible success, although much slower than was initially predicted. Although, gene therapies still at a fairly primitive stage, it is firmly science based. There is justifiable hope that with enhanced pathobiological understanding and biotechnological improvements, gene therapy will be a standard part of clinical practice within 20 years.

Lipid drug conjugate nanoparticle as a potential nanocarrier for the oral delivery of pemetrexed diacid: Formulation design, characterization, ex vivo, and in vivo assessment.

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Soni, Kriti; Mujtaba, Ali; Kohli, Kanchan

2017-10-01

The present work was to develop lipid drug conjugated (LDC) nanoparticles for the potential oral delivery of pemetrexed diacid (PTX) and evaluation of its in vitro, ex vivo and in vivo potentials. The LDC was prepared by salt formation of PTX with stearic acid and followed by cold homogenization technique to produce the LDC nanoparticles. FTIR analysis of LDC proved the presence of amide bond in LDC powder indicating the conjugation between drug and lipid. LDC nanoparticles was found to have particle size 121.9±1.85nm and zeta potential -51.6mV±1.23 and entrapment efficiency 81.0±0.89%. TEM images revealed spherical morphology and were in corroboration with particle size measurements. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the LDC as compared to plain drug solution and were confirmed by CLSM. MTT assay conformed significant% toxicity at the end of 24h and 48h. Furthermore, the AUC 0-24 of PTX from the optimized LDC nanoparticels was found to be 4.22 folds higher than that from PTX suspension on oral administration. Thus, LDC has high potential for the oral delivery of PTX in cancer therapy and future prospects for the industrial purpose. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene Therapy, Early Promises, Subsequent Problems, and Recent Breakthroughs

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Saeideh Razi Soofiyani

2013-08-01

Full Text Available Gene therapy is one of the most attractive fields in medicine. The concept of gene delivery to tissues for clinical applications has been discussed around half a century, but scientist’s ability to manipulate genetic material via recombinant DNA technology made this purpose to reality. Various approaches, such as viral and non-viral vectors and physical methods, have been developed to make gene delivery safer and more efficient. While gene therapy initially conceived as a way to treat life-threatening disorders (inborn errors, cancers refractory to conventional treatment, to date gene therapy is considered for many non–life-threatening conditions including those adversely influence on a patient’s quality of life. Gene therapy has made significant progress, including tangible success, although much slower than was initially predicted. Although, gene therapies still at a fairly primitive stage, it is firmly science based. There is justifiable hope that with enhanced pathobiological understanding and biotechnological improvements, gene therapy will be a standard part of clinical practice within 20 years.

Targeted Therapies for Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E

Targeted therapies have become standard therapies for patients with non-small cell lung cancer (NSCLC). A phase III trial of carboplatin and paclitaxel with and without bevacizumab in patients with advanced NSCLC with non-squamous histology demonstrated a statistically significant improvement in efficacy. In patients with NSCLC with an activating epidermal growth factor receptor (EGFR) mutation (defined as exon 19 deletion and exon 21 L858R point mutation), phase III trials of EGFR tyrosine kinase inhibitors (TKI) compared to platinum-based chemotherapy have demonstrated superior efficacy in the first-line setting. In patients with NSCLC with anaplastic lymphoma kinase (ALK) rearrangements, phase III trials of crizotinib have demonstrated superior efficacy compared to platinum-pemetrexed in the first-line setting and standard chemotherapy in the second-line setting. A second-generation ALK inhibitor, ceritinib, is available for patients who have progressed after or were intolerant of crizotinib. Crizotinib has also demonstrated activity on patients with ROS1 rearrangements, and BRAF inhibitors (dabrafenib, vemurafenib) have demonstrated activity in patients with NSCLC with BRAF V600E mutation. The oncogenic mutations that are susceptible to targeted therapy are mainly found in non-squamous NSCLC. The development of targeted therapy in patients with squamous NSCLC has been more challenging due to the genomic complexity observed in the squamous histology and the low prevalence of EGFR, ALK, and ROS1 molecular alterations. A phase III trial of cisplatin and gemcitabine with and without necitumumab in patients with advanced NSCLC with squamous histology demonstrated a statistically significant improvement in progression-free and overall survival.

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies.

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Okamoto, Isamu; Schuette, Wolfgang H W; Stinchcombe, Thomas E; Rodrigues-Pereira, José; San Antonio, Belén; Chen, Jian; Liu, Jingyi; John, William J; Zinner, Ralph G

2017-05-01

This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer. All patients received pemetrexed 500 mg/m 2 every 21 days with either of two carboplatin doses for up to 4-6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized. A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n = 105) received PCb5 in one trial and 78% (n = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses. Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, the results show that the PCb5 regimen was generally associated

Trimodality strategy for treating malignant pleural mesothelioma: results of a feasibility study of induction pemetrexed plus cisplatin followed by extrapleural pneumonectomy and postoperative hemithoracic radiation (Japan Mesothelioma Interest Group 0601 Trial).

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Hasegawa, Seiki; Okada, Morihito; Tanaka, Fumihiro; Yamanaka, Takeharu; Soejima, Toshinori; Kamikonya, Norihiko; Tsujimura, Tohru; Fukuoka, Kazuya; Yokoi, Kohei; Nakano, Takashi

2016-06-01

We conducted a prospective multi-institutional study to determine the feasibility of trimodality therapy (TMT) comprising induction chemotherapy followed by extrapleural pneumonectomy (EPP) and radiation therapy in Japanese patients with malignant pleural mesothelioma (MPM). Major eligibility criteria were histologically confirmed diagnosis of MPM, including clinical subtypes T0-3, N0-2, M0 disease; no prior treatment for the disease; age 20-75 years; Eastern Cooperative Oncology Group performance status 0 or 1; predicted postoperative forced expiratory volume >1000 ml in 1 s; written informed consent. Treatment methods comprised induction chemotherapy using pemetrexed (500 mg/m(2)) plus cisplatin (60 mg/m(2)) for three cycles, followed by EPP and postoperative hemithoracic radiation therapy (54 Gy). Primary endpoints were macroscopic complete resection (MCR) rate for EPP and treatment-related mortality for TMT. Forty-two eligible patients were enrolled: median age 64.5 (range 43-74) years; M:F = 39:3, clinical stage I:II:III = 14:13:15; histological type epithelioid were sarcomatoid; biphasic; others = 28:1:9:4. Of 42 patients, 30 completed EPP with MCR and 17 completed TMT. The trial met the primary endpoints, with an MCR rate of 71 % (30/42) and treatment-related mortality of 9.5 % (4/42). Overall median survival time and 2-year survival rate for 42 registered patients were 19.9 months and 42.9 %, respectively. Two-year relapse-free survival rate of 30 patients who completed EPP with MCR was 37.0 %. This phase II study met the predefined primary endpoints, but its risk/benefit ratio was not satisfactory.

Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

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Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

2010-11-01

Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. Copyright © 2010 Elsevier Ltd. All rights reserved.

Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

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Ming Li

Full Text Available To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC.A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS, progression-free survival (PFS, response rate (RR, and different types of toxicity. Hazard ratios (HRs, odds ratios (ORs and their 95% confidence intervals (CIs were pooled using RevMan software.Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC improved survival compared with other platinum-based regimens (PBR in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04, especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02. No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95-1.39, p = 0.15, respectively. Compared with PBR, PPC led to less grade 3-4 neutropenia and leukopenia but more grade 3-4 nausea. However, hematological toxicity analysis revealed significant heterogeneities.Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology.

Radioiodine therapy and subsequent pregnancy; Gravidez apos radioiodoterapia

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Brandao, Carmen Dolores G.; Miranda, Angelica E.; Corres, Nilson Duarte; Sieiro Neto, Lino; Corbo, Rossana; Vaisman, Mario [Hospital Universitario Clementino Fraga Filho (UFRJ), Rio de Janeiro, RJ (Brazil). Dept. of Endocrinology and Nuclear Medicine; Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil); Hospital dos Servidores do Estado do Rio de Janeiro, RJ (Brazil); E-mail: loloi@zaz.com.br

2007-06-15

Objectives: To evaluate abortion and fetal congenital anomaly rates in women previously submitted to radioiodine therapy for differentiated thyroid carcinoma. Study design: A case-control study of 108 pregnant women, 48 cases whose pregnancies were evaluated after they had undergone radioiodine therapy for differentiated thyroid carcinoma, and the control group consisted of 60 healthy pregnant women. Results: Of a total of 66 pregnancies, 14 conceived within the first year, 51 one or more years after the last administration of {sup 131}I, the medical record of one patient was not available. The interval between the last radioiodine therapy administration and conception ranged from 1 month to 10 years. There were a total of 4 miscarriages, 2 of them for unknown reasons. There was one case of congenital anomaly and two preterms birth. Nine women presented the following pregnancy events: placental insufficiency, hypertensive crisis, placental detachment, risk of miscarriage, preterm labour and four miscarriages. No statistical difference was observed between the studied and control groups. Conclusion: Radioiodine was followed by no significant increase in untoward effects in neither the pregnancy nor the offspring. (author)

Cost-effectiveness of pemetrexed in combination with cisplatin as first line treatment for patients with advanced non-squamous non-small-cell

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Jonathan González García

2017-01-01

Full Text Available Introduction: Lung cancer is the third most frequent neoplastic tumour in Spain, with around 27 000 new cases diagnosed per year; 80-95% of these are non-small-cell cancer (NSCLC, and the majority of cases are diagnosed in advanced stages of the disease, and for this reason it is one of the oncologic conditions with higher mortality rates (21.4% mean survival at 5 years. The main treatment regimens used for first-line treatment of NSCLC are: isplatin/pemetrexed (cis/pem, cisplatin/gemcitabine/ bevacizumab (cis/gem/bev, and carboplatin/paclitaxel/ bevacizumab (carb/pac/bev. The objective of this study was to evaluate the cost-effectiveness ratio of antineoplastic 1st line NSCLC treatment regimens, from the point of view of hospital management. Methodology: A cost-efficacy mathematical model was prepared, based on a decision tree. The efficacy variable was Progression Free Survival, obtained from the PARAMOUNT, AVAIL and SAIL Phase III clinical trials. The study was conducted from the perspective of the hospital management, considering only the direct costs of drug acquisition. A deterministic sensitivity analysis was conducted to confirm the robustness of outcomes. Results: The PFS obtained in clinical trials with cis/pem, cis/ gem/bev and carb/pac/bev was: 6.9, 6.7 and 6.2 months, respectively. Based on our model, the mean cost of treatment per patient for these regimens was: 19 942 €, 15 594 € and 36 095 €, respectively. The incremental cost-effectiveness ratio per month of additional PFS between cis/pem and cis/gem/bev was 19 303 €. Estimating a 30% reduction in acquisition costs for pemetrexed (Alimta®Eli Lilly Nederland B.V., due to the forthcoming launch of generic medications, the cis/pem treatment would become the predominant alternative for 1st line treatment of NSCLC patients, by offering the best health results at a lower cost.

Second-line combination therapies in nonsmall cell lung cancer without known driver mutations

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Maria-Virginia Bluthgen

2015-12-01

Full Text Available In advanced nonsmall cell lung cancer (NSCLC patients, platinum-based combination chemotherapy is standard treatment in the first-line setting; however, the large majority of patients ultimately progress. For more than a decade, single-agent therapy with docetaxel, pemetrexed or erlotinib has been the standard of care after failure with platinum salts, showing some benefit over best supportive care. Nonetheless, prognosis remains poor and new second-line strategies are urgently needed. Combinations of cytotoxic agents, including rechallenge with platinum salts, do not offer clear benefit over single-agent therapy for the majority of patients. In patients without a known tumoural oncogenic driver mutation, regimens based on combinations of targeted agents have shown promising results; however, a clear role in therapeutic management is yet to be established. Some success has been reported in recent research combining a cytotoxic agent with targeted therapies. In this review, we summarise published data for the various strategies evaluated over the past decade in second-line treatment of NSCLC patients without a known driver mutation. We focus on combination treatments and consider future perspectives, including the need to identify predictive markers to support personalised therapeutic strategies.

Maintenance therapy in advanced non-small cell lung cancer: current status and future implications.

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Stinchcombe, Thomas E; Socinski, Mark A

2011-01-01

Maintenance therapy for patients with advanced non-small cell lung cancer has been an area of intense investigation. Maintenance therapy has been divided into two broad categories: continuation maintenance when the chemotherapy or targeted agent was part of a defined number of cycles of combination therapy and in the absence of disease progression is continued as a single agent or switch maintenance when a third agent is initiated after four cycles of platinum-based double-agent chemotherapy in the absence of disease progression. Two monoclonal antibodies, cetuximab and bevacizumab, are used as continuation maintenance, but the incremental benefit of the maintenance therapy with these agents is undetermined. Phase III trials have not revealed an overall survival benefit for continuation maintenance chemotherapy, and this approach should be considered investigational. Phase III trials have demonstrated an improvement in overall survival with switch maintenance therapy with pemetrexed compared with placebo in patients with nonsquamous histology and erlotinib compared with placebo. Phase III trials have not revealed an improvement in quality of life with maintenance therapy. In the trials of maintenance therapy, 30 to 40% of patients enrolled in the observation or placebo arm did not receive second-line therapy, and among the patients who did receive second-line therapy, there was significant heterogeneity in the therapy. The development of maintenance therapy has raised issues about the role of treatment-free intervals in routine clinical care, trial design issues such as the optimal endpoint, the ethics of a placebo arm, and the implications of maintenance therapy for first-line trials.

Phase III study by the Norwegian lung cancer study group

DEFF Research Database (Denmark)

Grønberg, Bjørn H; Bremnes, Roy M; Fløtten, Oystein

2009-01-01

PURPOSE To compare pemetrexed/carboplatin with a standard regimen as first-line therapy in advanced non-small-cell lung cancer NSCLC. PATIENTS AND METHODS Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were randomly assigned to receive pemetrexed 500 mg/m(2) plus carboplatin......, and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the lung cancer-specific module LC13 during the first 20 weeks. Secondary end points were overall survival and toxicity. Results Four hundred thirty-six eligible patients were enrolled...

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

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Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

2016-01-19

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma.

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Ak, Guntulu; Metintas, Selma; Akarsu, Muhittin; Metintas, Muzaffer

2015-07-09

We aimed to evaluate the efficiency and safety of cis/carboplatin plus gemcitabine, which was previously used for mesothelioma but with no recorded proof of its efficiency, compared with cis/carboplatin plus pemetrexed, which is known to be effective in mesothelioma, in comparable historical groups of malignant pleural mesothelioma. One hundred and sixteen patients received cis/carboplatin plus pemetrexed (group 1), while 30 patients received cis/carboplatin plus gemcitabine (group 2) between June 1999 and June 2012. The two groups were compared in terms of median survival and adverse events to chemotherapy. The mean ages of groups 1 and 2 were 60.7 and 60.8 years, respectively. Most of the patients (78.1%) had epithelial type tumors, and 47% of the patients had stage IV disease. There was no difference between the two groups in terms of age, gender, asbestos exposure, histology, stage, Karnofsky performance status, presence of pleurodesis, prophylactic radiotherapy, second-line chemotherapy and median hemoglobin and serum albumin levels. The median survival time from diagnosis to death or the last day of follow up with a 95% confidence interval was 12 ± 0.95 months (95% CI: 10.15-13.85) for group 1 and 11.0 ± 1.09 months (95% CI: 8.85-13.15) for group 2 (Log-Rank: 0.142; p = 0.706). The median survival time from treatment to death or the last day of follow-up with a 95% confidence interval was 11.0 ± 0.99 months (95% CI: 9.06-12.94) for group 1 and 11.0 ± 1.52 months (95% CI: 8.02-13.97) for group 2 (Log-Rank: 0.584; p = 0.445). The stage and Karnofsky performance status were found to be significant variables on median survival time by univariate analysis. After adjusting for the stage and Karnofsky performance status, the chemotherapy schema was not impressive on median survival time (OR: 0.837; 95% CI: 0.548-1.277; p = 0.409). The progression free survival was 7.0 ± 0.61 months for group I and 6.0 ± 1.56 months for group II (Log-Rank: 0.522; p = 0

Clinical roundtable monograph: Recent advances in taxanes for the first-line treatment of advanced non-small cell lung cancer.

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Socinski, Mark A; Govindan, Ramaswamy; Spigel, David

2012-10-01

Treatments for non-small cell lung cancer (NSCLC) are based on the broad categories of squamous or non-squamous histology. Frontline treatment options include pemetrexed and cisplatin, pemetrexed and a taxane, gemcitabine with cisplatin, and the addition of bevacizumab to a taxane and carboplatin. Pemetrexed is used for maintenance therapy for non-squamous NSCLC, whereas patients with squamous NSCLC lack easy options for maintenance therapy. nab-Paclitaxel overcomes the solubility and toxicity issues of solvent-based paclitaxel, and the albumin in nab-paclitaxel improves the concentration of the drug in the tumor. A recent phase III trial in NSCLC compared nab-paclitaxel with carboplatin versus solvent-based paclitaxel with carboplatin, and found improved overall response rates (ORRs) in the nab-paclitaxel arm (33% vs 25%; P=.005). In a subset analysis, NSCLC patients with squamous histology had a higher ORR (41%) with nab-paclitaxel than with solvent-based paclitaxel (24%; P<.001). Another subset analysis found that patients ages 70 years and older had improved overall survival (median 19.9 months) with nab-paclitaxel compared with solvent-based paclitaxel (median 10.4 months; P=.009). Patients in the nab-paclitaxel arm had less neuropathy, less hearing loss, and fewer interruptions in daily living than patients in the solvent-based paclitaxel arm.

Feasibility Study of Sequentially Alternating EGFR-TKIs and Chemotherapy for Patients with Non-small Cell Lung Cancer.

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Takemura, Yoshizumi; Chihara, Yusuke; Morimoto, Yoshie; Tanimura, Keiko; Imabayashi, Tatsuya; Seko, Yurie; Kaneko, Yoshiko; Date, Koji; Ueda, Mikio; Arimoto, Taichiro; Iwasaki, Yoshinobu; Takayama, Koichi

2018-04-01

The purpose of this trial was to evaluate the feasibility and efficacy of alternating platinum-based doublet chemotherapy with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC harboring an EGFR mutation were enrolled. All patients underwent induction chemotherapy by sequentially alternating pemetrexed/cisplatin/bevacizumab and EGFR-TKIs followed by maintenance therapy with pemetrexed/bevacizumab and EGFR-TKIs. The primary outcome was the completion rate of the induction therapy. Eighteen eligible patients were enrolled between May 2011 and March 2016. The completion rate of induction therapy was 72.2% (13/18). Unfortunately, one patient developed grade 4 acute renal injury, but no other serious complications concerning this protocol were observed. Furthermore, diarrhea, rashes, and hematological adverse effects were mild. The completion rate of induction therapy was promising. Alternating chemotherapy and EGFR-TKIs should be further investigated regarding feasibility and efficacy. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Coverage of Deep Cutaneous Wounds Using Dermal Template in Combination with Negative-pressure Therapy and Subsequent Skin Graft

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Chang, Alexandre A.; Lobato, Rodolfo C.; Nakamoto, Hugo A.; Tuma, Paulo; Ferreira, Marcus C.

2014-01-01

Background: We consider the use of dermal matrix associated with a skin graft to cover deep wounds in the extremities when tendon and bone are exposed. The objective of this article was to evaluate the efficacy of covering acute deep wounds through the use of a dermal regeneration template (Integra) associated with vacuum therapy and subsequent skin grafting. Methods: Twenty patients were evaluated prospectively. All of them had acute (up to 3 weeks) deep wounds in the limbs. We consider a deep wound to be that with exposure of bone, tendon, or joint. Results: The average area of integration of the dermal regeneration template was 86.5%. There was complete integration of the skin graft over the dermal matrix in 14 patients (70%), partial integration in 5 patients (25%), and total loss in 1 case (5%). The wound has completely closed in 95% of patients. Conclusions: The use of Integra dermal template associated with negative-pressure therapy and skin grafting showed an adequate rate of resolution of deep wounds with low morbidity. PMID:25289363

Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells

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Buqué Aitziber

2012-04-01

Full Text Available Abstract Background Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC, and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet. Results In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and –independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis. Conclusions We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and –independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.

[Therapy-resistant and therapy-refractory arterial hypertension].

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Wallbach, M; Koziolek, M J

2018-05-02

Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, a structured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

Development and optimization of targeted radionuclide tumor therapy using folate based radiopharmaceuticals

CERN Document Server

Reber, Josefine Astrid

The folate receptor (FR) has been used for a quarter of a century as a tumor-associated target for selective delivery of drugs and imaging agents to cancer cells. While several folic acid radioconjugates have been successfully employed for imaging purposes in (pre)clinical studies, a therapeutic application of folic acid radioconjugates has not yet reached the critical stage which would allow a clinical translation. Due to a substantial expression of the FR in the proximal tubule cells, radiofolates accumulate in the kidneys which are at risk of damage by particle-radiation. To improve this situation, we aimed to develop and evaluate strategies for the performance of FR-targeted radionuclide therapy by decreasing the renal uptake of radiofolates and thereby reducing potential nephrotoxic effects. Two different strategies were investigated. First, the combination of radiofolates with chemotherapeutic agents such as pemetrexed (PMX) and 5-fluorouracil (5-FU) and secondly, an approach based on radioiodinated fol...

Maintenance treatment with chemotherapy and immunotherapy in non-small cell lung cancer:A case report.

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Anabella eLlanos

2012-10-01

Full Text Available A 53-year-old woman was diagnosed with lung adenocarcinoma state IV (synchronous pleural involvement in April 2009. First-line systemic treatment included 6 cycles of Carboplatin, Paclitaxel, and Bevacizumab. Partial response was achieved. Maintenance therapy with Bevacizumab and Pemetrexed was given from September 2009 to February 2010. No response changes were observed. Immunotherapy was initiated, and then Pemetrexed was given with the same disease status. Both treatments were well tolerated. Immunotherapy toxicity included reaction at the site of injection grade 2. At present, the patient is still on this treatment. Given the poor prognosis of patients with advanced lung cancer, the combination of both treatments during the stable phase of the disease may improve progression-free survival.

Osteoblastic flare in a patient with advanced gastric cancer after treatment with pemetrexed and oxaliplatin: implications for response assessment with RECIST criteria

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Simoncini Edda

2007-06-01

Full Text Available Abstract Background The RECIST guidelines are commonly used in phase II and III clinical trials. The correct definition of response can be controversial in some situations, as in the case we describe. Case presentation A 43 year-old man with advanced gastric cancer was enrolled in a phase II trial where he was treated with pemetrexed 500 mg/m2 plus oxaliplatin 120 mg/m2 every 3 weeks. At baseline, the target lesions were lymph-nodes, and the non-target lesions were small pulmonary nodules. At first re-evaluation, the target lesions showed partial response and the non-target lesions showed complete response, but new diffuse osteoblastic lesions appeared. The investigator decided to continue treatment until the second re-evaluation. CT scan confirmed the response of the target and non-target lesions, while the osteoblastic lesions did not change. Conclusion The appearance of osteoblastic lesions after an active antitumor treatment, a phenomenon known as flare, can complicate the definition of the best overall response using RECIST criteria. This possibility should be considered by oncologists involved in clinical trials.

Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea

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Gerber, David E.; Schiller, Joan H.

2013-01-01

Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting. PMID:23401441

Avaliação económica do erlotinib, docetaxel, pemetrexedo e tratamento de suporte no tratamento de segunda ou terceira linhas de doentes com cancro do pulmão de não pequenas células An economic analysis of erlotinib, docetaxel, pemetrexed and best supportive care as second or third line treatment of non-small cell lung cancer

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A Araújo

2008-12-01

Full Text Available Objectivo: Avaliar o custo-efectividade de erlotinib na segunda ou terceira linha do tratamento do cancro do pulmão de não pequenas células (CPNPC avançado ou metastizado versus docetaxel, pemetrexedo ou tratamento de suporte. Material e métodos: Análises de minimização de custos e custo-utilidade. Horizonte temporal: dois anos. Perspectiva do Sistema Nacional de Saúde (SNS português. Sobrevivência e tempo até progressão obtidos a partir de três ensaios clínicos. Análise-base inclui doentes com CPNPC avançado ou metastizado em segunda ou terceira linhas. Anos de vida ajustados pela qualidade (ou QALY obtidos a partir de estudo no Reino Unido. Consumo de recursos estimado por painel de peritos portugueses. Incluíram-se apenas custos directos, obtidos a partir de fontes oficiais (preços actualizados para 2008. Taxa de actualização anual: 5%. Análises de sensibilidade: diferentes subpopulações, horizonte temporal a três anos e análise probabilística. Resultados: O custo total/doente foi menor com erlotinib (26 478€ versus docetaxel (29 262€ ou pemetrexedo (32 762€ e superior versus tratamento de suporte (16 112€. Obtiveram-se QALY/doente mais elevados com erlotinib (0,250 versus docetaxel (0,225, pemetrexedo (0,241 ou tratamento de suporte (0,186. Assim, o erlotinib mostrou-se “dominante” em segunda ou terceira linhas versus docetaxel e pemetrexedo. A análise de sensibilidade comprova a robustez dos resultados. Conclusões: A substituição de docetaxel ou pemetrexedo por erlotinib poderia contribuir para uma redução anual dos gastos do SNS que se estima (taxas substituição: 5%-65% com uma variação entre 135 046€-1 755 602€ e entre 291 801€ -3 793 409€, respectivamente, e com ganho em termos de QALY.Aim: Evaluate costs and benefits of erlotinib as 2nd or 3rd line treatment of advanced or metastatic nonsmall cell lung cancer (NSCLC versus docetaxel, pemetrexed and best supportive care. Materials

Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer.

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Pérol, Maurice; Chouaid, Christos; Pérol, David; Barlési, Fabrice; Gervais, Radj; Westeel, Virginie; Crequit, Jacky; Léna, Hervé; Vergnenègre, Alain; Zalcman, Gérard; Monnet, Isabelle; Le Caer, Hervé; Fournel, Pierre; Falchero, Lionel; Poudenx, Michel; Vaylet, Fabien; Ségura-Ferlay, Céline; Devouassoux-Shisheboran, Mojgan; Taron, Miquel; Milleron, Bernard

2012-10-01

This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy. Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS). PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events. Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.

Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy

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Allodji, Rodrigue S., E-mail: rodrigue.allodji@gustaveroussy.fr [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France); Schwartz, Boris; Veres, Cristina; Haddy, Nadia; Rubino, Carole; Le Deley, Marie-Cécile; Labbé, Martine; Diop, Fara; Jackson, Angela; Dayet, Florent; Benabdennebi, Aymen; Llanas, Damien; Vu Bezin, Jérémi [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France); Chavaudra, Jean; Lefkopoulos, Dimitri [Gustave Roussy, Villejuif (France); Deutsch, Eric [Gustave Roussy, Villejuif (France); Inserm, UMR 1030, Villejuif (France); Oberlin, Odile [Gustave Roussy, Villejuif (France); Vathaire, Florent de; Diallo, Ibrahima [Inserm, Radiation Epidemiology Team, CESP-Unit 1018, Villejuif (France); Gustave Roussy, Villejuif (France); Paris Sud University, Orsay (France)

2015-11-01

Purpose: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. Methods and Materials: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Results: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m{sup 2}. Conclusions: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.

Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy

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Allodji, Rodrigue S.; Schwartz, Boris; Veres, Cristina; Haddy, Nadia; Rubino, Carole; Le Deley, Marie-Cécile; Labbé, Martine; Diop, Fara; Jackson, Angela; Dayet, Florent; Benabdennebi, Aymen; Llanas, Damien; Vu Bezin, Jérémi; Chavaudra, Jean; Lefkopoulos, Dimitri; Deutsch, Eric; Oberlin, Odile; Vathaire, Florent de; Diallo, Ibrahima

2015-01-01

Purpose: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. Methods and Materials: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Results: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trend became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m"2. Conclusions: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.

Successful treatment of thyroid storm presenting as recurrent cardiac arrest and subsequent multiorgan failure by continuous renal replacement therapy

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Han Soo Park

2017-03-01

Full Text Available Thyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF. A 22-year-old female patient with a 10-year history of Graves’ disease was transferred to our emergency department (ED. She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient’s dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment.

Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma

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Gennatas, Spyridon; Stanway, Susana J; Thomas, Robert; Min, Toon; Shah, Riyaz; O’Brien, Mary ER; Popat, Sanjay

2013-01-01

Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses. Spontaneous pneumothoraces as a result of response to anti-cancer therapy are rare in oncology but have been documented in a number of tumour types including lung cancer. This includes cytotoxic chemotherapy as well as molecular targeted agents such as gefitinib and Bevacizumab. These often require chest drain insertion or surgical intervention with associated morbidity and mortality. They have also been associated with response to treatment. This is the first report we are aware of documenting pneumothorax as response to crizotinib therapy. A 48-year-old Caucasian male presented with a Stage IV, TTF1 positive, EGFR wild-type adenocarcinoma of the lung. He received first line chemotherapy with three cycles of cisplatin-pemetrexed chemotherapy with a differential response, and then second-line erlotinib for two months before further radiological evidence of disease progression. Further analysis of his diagnostic specimen identified an ALK rearrangement by fluorescence in situ hybridization (FISH). He was commenced on crizotinib therapy 250 mg orally twice daily. At his 4-week assessment he had a chest radiograph that identified a large left-sided pneumothorax with disease response evident on the right. Chest CT confirmed a 50% left-sided pneumothorax on a background of overall disease response. A chest tube was inserted with complete resolution of the pneumothorax that did not recur following its removal. Our case demonstrates this potential complication of crizotinib therapy and we therefore recommend that pneumothorax be considered in patients on crizotinib presenting with high lung metastatic burden and with worsening dyspnoea

Subsequent Chemotherapy and Treatment Patterns After Abiraterone Acetate in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

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de Bono, Johann S; Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; Small, Eric J; Shore, Neal D; Fizazi, Karim; De Porre, Peter; Kheoh, Thian; Li, Jinhui; Todd, Mary B; Ryan, Charles J; Flaig, Thomas W

2017-04-01

Treatment patterns for metastatic castration-resistant prostate cancer (mCRPC) have changed substantially in the last few years. In trial COU-AA-302 (chemotherapy-naïve men with mCRPC), abiraterone acetate plus prednisone (AA) significantly improved radiographic progression-free survival and overall survival (OS) when compared to placebo plus prednisone (P). This post hoc analysis investigated clinical responses to docetaxel as first subsequent therapy (FST) among patients who progressed following protocol-specified treatment with AA, and characterized subsequent treatment patterns among older (≥75 yr) and younger (AA arm received subsequent treatment with one or more agents approved for mCRPC. Efficacy analysis was performed for patients for whom baseline and at least one post-baseline prostate-specific antigen (PSA) values were available. Baseline and at least one post-baseline PSA values were available for 100 AA patients who received docetaxel as FST. While acknowledging the limitations of post hoc analyses, 40% (40/100) of these patients had an unconfirmed ≥50% PSA decline with first subsequent docetaxel therapy, and 27% (27/100) had a confirmed ≥50% PSA decline. The median docetaxel treatment duration among these 100 patients was 4.2 mo. Docetaxel was the most common FST among older and younger patients from each treatment arm. However, 43% (79/185) of older patients who progressed on AA received no subsequent therapy for mCRPC, compared with 17% (60/361) of younger patients. Patients with mCRPC who progress with AA treatment may still derive benefit from subsequent docetaxel therapy. These data support further assessment of treatment patterns following AA treatment for mCRPC, particularly among older patients. ClinicalTrials.gov NCT00887198. Treatment patterns for advanced prostate cancer have changed substantially in the last few years. This additional analysis provides evidence of clinical benefit for subsequent chemotherapy in men with advanced

Cost-effectiveness analysis of additional bevacizumab to pemetrexed plus cisplatin for malignant pleural mesothelioma based on the MAPS trial.

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Zhan, Mei; Zheng, Hanrui; Xu, Ting; Yang, Yu; Li, Qiu

2017-08-01

Malignant pleural mesothelioma (MPM) is a rare malignancy, and pemetrexed/cisplatin (PC) is the gold standard first-line regime. This study evaluated the cost-effectiveness of the addition of bevacizumab to PC (with maintenance bevacizumab) for unresectable MPM based on a phase III trial that showed a survival benefit compared with chemotherapy alone. To estimate the incremental cost-effectiveness ratio (ICER) of the incorporation of bevacizumab, a Markov model based on the MAPS trial, including the disease states of progression-free survival, progressive disease and death, was used. Total costs were calculated from a Chinese payer perspective, and health outcomes were converted into quality-adjusted life year (QALY). Model robustness was explored in sensitivity analyses. The addition of bevacizumab to PC was estimated to increase the cost by $81446.69, with a gain of 0.112 QALYs, resulting in an ICER of $727202.589 per QALY. In both one-way sensitivity and probabilistic sensitivity analyses, the ICER exceeded the commonly accepted willingness-to-pay threshold of 3 times the gross domestic product per capita of China ($23970.00 per QALY). The cost of bevacizumab had the most important impact on the ICER. The combination of bevacizumab with PC chemotherapy is not a cost-effective treatment option for MPM in China. Given its positive clinical value and extremely low incidence of MPM, an appropriate price discount, assistance programs and medical insurance should be considered to make bevacizumab more affordable for this rare patient population. Copyright © 2017 Elsevier B.V. All rights reserved.

Gastric ulcer treatment: cure of Helicobacter pylori infection without subsequent acid-suppressive therapy: is it effective?

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van Zanten, Sander Veldhuyzen; van der Knoop, Bloeme

2008-06-01

Whether it is a requirement to continue with anti-secretory therapy following anti-Helicobacter therapy in H. pylori positive gastric ulcers is an important question. As gastric ulcers tend to heal more slowly than duodenal ulcers, may be asymptomatic or only causing mild symptoms and success at curing H. pylori with current fist line therapies is 80% at best, clinicians will likely err on the side of caution and continue acid suppressive therapy to ensure healing of gastric ulcers. This is certainly recommended when dealing with bleeding ulcers.

SU-E-T-590: Optimizing Magnetic Field Strengths with Matlab for An Ion-Optic System in Particle Therapy Consisting of Two Quadrupole Magnets for Subsequent Simulations with the Monte-Carlo Code FLUKA

International Nuclear Information System (INIS)

Baumann, K; Weber, U; Simeonov, Y; Zink, K

2015-01-01

Purpose: Aim of this study was to optimize the magnetic field strengths of two quadrupole magnets in a particle therapy facility in order to obtain a beam quality suitable for spot beam scanning. Methods: The particle transport through an ion-optic system of a particle therapy facility consisting of the beam tube, two quadrupole magnets and a beam monitor system was calculated with the help of Matlab by using matrices that solve the equation of motion of a charged particle in a magnetic field and field-free region, respectively. The magnetic field strengths were optimized in order to obtain a circular and thin beam spot at the iso-center of the therapy facility. These optimized field strengths were subsequently transferred to the Monte-Carlo code FLUKA and the transport of 80 MeV/u C12-ions through this ion-optic system was calculated by using a user-routine to implement magnetic fields. The fluence along the beam-axis and at the iso-center was evaluated. Results: The magnetic field strengths could be optimized by using Matlab and transferred to the Monte-Carlo code FLUKA. The implementation via a user-routine was successful. Analyzing the fluence-pattern along the beam-axis the characteristic focusing and de-focusing effects of the quadrupole magnets could be reproduced. Furthermore the beam spot at the iso-center was circular and significantly thinner compared to an unfocused beam. Conclusion: In this study a Matlab tool was developed to optimize magnetic field strengths for an ion-optic system consisting of two quadrupole magnets as part of a particle therapy facility. These magnetic field strengths could subsequently be transferred to and implemented in the Monte-Carlo code FLUKA to simulate the particle transport through this optimized ion-optic system

Treatment of stage IV non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

Science.gov (United States)

Socinski, Mark A; Evans, Tracey; Gettinger, Scott; Hensing, Thomas A; VanDam Sequist, Lecia; Ireland, Belinda; Stinchcombe, Thomas E

2013-05-01

Stage IV non-small cell lung cancer (NSCLC) is a treatable, but not curable, clinical entity in patients given the diagnosis at a time when their performance status (PS) remains good. A systematic literature review was performed to update the previous edition of the American College of Chest Physicians Lung Cancer Guidelines. The use of pemetrexed should be restricted to patients with nonsquamous histology. Similarly, bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1; however, the data now suggest it is safe to use in those patients with treated and controlled brain metastases. Data at this time are insufficient regarding the safety of bevacizumab in patients receiving therapeutic anticoagulation who have an ECOG PS of 2. The role of cetuximab added to chemotherapy remains uncertain and its routine use cannot be recommended. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line therapy are the recommended treatment of those patients identified as having an EGFR mutation. The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression. The use of second- and third-line therapy in stage IV NSCLC is recommended in those patients retaining a good PS; however, the benefit of therapy beyond the third-line setting has not been demonstrated. In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred. Palliative care should be initiated early in the course of therapy for stage IV NSCLC. Significant advances continue to be made, and the treatment of stage IV NSCLC has become nuanced and specific for particular histologic subtypes and clinical patient characteristics and according to the presence of specific genetic mutations.

Clinical decision-making and health-related quality of life during first-line and maintenance therapy in patients with advanced non-small cell lung cancer (NSCLC): findings from a real-world setting.

Science.gov (United States)

Sztankay, Monika; Giesinger, Johannes Maria; Zabernigg, August; Krempler, Elisabeth; Pall, Georg; Hilbe, Wolfgang; Burghuber, Otto; Hochmair, Maximilian; Rumpold, Gerhard; Doering, Stephan; Holzner, Bernhard

2017-08-23

Maintenance therapy (MT) with pemetrexed has been shown to improve overall and progression-free survival of patients with non-squamous non-small cell lung cancer (NSCLC), without impairing patients' health-related quality of life (HRQOL) substantially. Comprehensive data on HRQOL under real-life conditions are necessary to enable informed decision-making. This study aims to (1) assess HRQOL during first-line chemotherapy and subsequent MT and (2) record patients' and physicians' reasons leading to clinical decisions on MT. Patients treated for NSCLC at three Austrian medical centres were included. HRQOL was assessed at every chemotherapy cycle using the EORTC QLQ-C30/+LC13 questionnaire. Semi-structured interviews were conducted before MT initiation and at the time of discontinuation to evaluate patients' and physicians' reasons for treatment decisions. Longitudinal QOL analysis was based on linear mixed models. Sixty-one (73%) out of 84 patients were considered for MT. Thirty-six patients (43%) received MT and 29 (35%) discontinued therapy. Decisions on MT initiation (in 20 cases by the physician vs 4 by the patient) and discontinuation (19 vs 10) were mainly voiced by the physician. Treatment toxicity of first-line chemotherapy was the main reason for rejection of MT in patients with stable disease and was more often indicated by patients than clinicians. HRQOL data were collected from 83 patients at 422 assessment time points and indicated significantly lower symptom severity during MT compared with first-line therapy for nausea and vomiting (p = 0.006), sleep disturbances (p loss (p = 0.043), constipation (p = 0.017) and chest pain (p = 0.022), and a deterioration in emotional functioning (p = 0.023) and cognitive functioning (p = 0.044) during MT. Our results indicate that HRQOL and symptom burden improve between first-line treatment to MT in some respects, although some late toxicity persists. Discrepancies between patients' and physicians

Photobiomodulation therapy on wound treatment subsequent to Q-switched Nd: YAG laser tattoo removal in rat model.

Science.gov (United States)

Imrigha, Nada Abusalah Almabrouk; Bidin, Noriah; Lau, Pik Suan; Musa, Nurfatin; Zakaria, Nurlaily; Krishnan, Ganesan

2017-10-01

Q-switched Nd: YAG laser is the most effective laser for tattoo removal. Photobiomodulation (PBM) therapy is an alternative method applied to accelerate the wound healing. This paper investigated the effects of PBM therapy using 808 nm diode laser on tattooed skin after laser tattoo removal. Forty-five rats were selected and tattooed with black ink on their dorsal, and then distributed into three groups. G0 was received non-laser irradiation. G1 was treated by laser tattoo removal using 1064 nm with energy density of 3.4 J/cm 2 without PBM therapy, while G2 was treated daily with PBM therapy using 808 nm diode laser of 5 J/cm 2 after a single session of laser tattoo removal. The effects of tattoo removal and healing progress of the wound were analyzed using histological studies. Findings showed 808 nm laser promotes the healing process through enhancing epithelialization and collagen deposition. Moreover, PBM therapy stimulated immune cells to improve phagocytosis process for removing the tattoo ink fragments effectively. The PBM therapy treated group was capable of improving the healing process and increasing the quality of skin following the laser tattoo removal. It was also found that stimulation of cellular function by PBM therapy increased tattoo clearance efficiency. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association Between Facility-Level Utilization of Non-pharmacologic Chronic Pain Treatment and Subsequent Initiation of Long-Term Opioid Therapy.

Science.gov (United States)

Carey, Evan P; Nolan, Charlotte; Kerns, Robert D; Ho, P Michael; Frank, Joseph W

2018-05-01

Expert guidelines recommend non-pharmacologic treatments and non-opioid medications for chronic pain and recommend against initiating long-term opioid therapy (LTOT). We examined whether veterans with incident chronic pain receiving care at facilities with greater utilization of non-pharmacologic treatments and non-opioid medications are less likely to initiate LTOT. Retrospective cohort study PARTICIPANTS: Veterans receiving primary care from a Veterans Health Administration facility with incident chronic pain between 1/1/2010 and 12/31/2015 based on either of 2 criteria: (1) persistent moderate-to-severe patient-reported pain and (2) diagnoses "likely to represent" chronic pain. The independent variable was facility-level utilization of pain-related treatment modalities (non-pharmacologic, non-opioid medications, LTOT) in the prior calendar year. The dependent variable was patient-level initiation of LTOT (≥ 90 days within 365 days) in the subsequent year, adjusting for patient characteristics. Among 1,094,569 veterans with incident chronic pain from 2010 to 2015, there was wide facility-level variation in utilization of 10 pain-related treatment modalities, including initiation of LTOT (median, 16%; range, 5-32%). Veterans receiving care at facilities with greater utilization of non-pharmacologic treatments were less likely to initiate LTOT in the year following incident chronic pain. Conversely, veterans receiving care at facilities with greater non-opioid and opioid medication utilization were more likely to initiate LTOT; this association was strongest for past year facility-level LTOT initiation (adjusted rate ratio, 2.10; 95% confidence interval, 2.06-2.15, top vs. bottom quartile of facility-level LTOT initiation in prior calendar year). Facility-level utilization patterns of non-pharmacologic, non-opioid, and opioid treatments for chronic pain are associated with subsequent patient-level initiation of LTOT among veterans with incident chronic pain

Treatment of malignant pleural mesothelioma

International Nuclear Information System (INIS)

Yusa, Toshikazu

2007-01-01

In Japan, it is predicted that mesothelioma will rapidly increase in the future. Malignant pleural mesothelioma that accounts for approximately 90% of mesothelioma as a whole has a median survival time of approximately nine months which is considered a poor prognosis. As for the treatment of this disease, extrapleural pneumonectomy or pleurectomy/decortication are available for those patients who can be surgically operated on. However, since a complete cure rate is low when only surgical treatment is performed, generally a multimodality treatment is performed wherein chemotherapy and/or radiotherapy are combined. For chemotherapy, a large-scale randomized phase III study demonstrated that a treatment using two agents: pemetrexed, which is a new multitargeted antifolate, and cisplatin is effective. Pemetrexed will be the drug of first choice for mesothelioma in the future. As other treatment methods, chemohyperthermia, treatments using various kinds of cytokines and angiogenesis inhibitors, genetic treatment and photodynamic therapy have been attempted. The current treatment results for this disease are very poor, and there has been a strong demand for establishing an effective treatment method. (author)

Thymidylate synthase protein expression levels remain stable during paclitaxel and carboplatin treatment in non-small cell lung cancer

DEFF Research Database (Denmark)

Jakobsen, Jan Nyrop; Santoni-Rugiu, Eric; Sørensen, Jens Benn

2014-01-01

BACKGROUND: Thymidylate synthase (TS) is a potential predictive marker for efficacy of treatment with pemetrexed. The current study aimed at investigating whether TS expression changes during non-pemetrexed chemotherapy of non-small cell lung cancer (NSCLC), thus making rebiopsy necessary for dec...

A cost-effectiveness analysis of first-line induction and maintenance treatment sequences in patients with advanced nonsquamous non-small-cell lung cancer in France

Directory of Open Access Journals (Sweden)

Taipale K

2017-08-01

Full Text Available Kaisa Taipale,1 Katherine B Winfree,2 Mark Boye,2 Mickael Basson,3 Ghassan Sleilaty,4 James Eaton,5 Rachel Evans,5 Christos Chouaid6 1Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Corporate Affairs, Lilly France, Neuilly-sur-Seine, 4Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France; 5ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK; 6Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France Background: Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS and overall survival (OS relative to gemcitabine + cisplatin (induction sequences or best supportive care (BSC (maintenance sequences. Modeled health-care benefits were expressed as life-years (LYs and quality-adjusted LYs (QALYs (estimated using French EuroQol five-dimension questionnaire tariffs. The study was conducted from the payer perspective (National Health Insurance. Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results: Base-case results showed pemetrexed

Hadron Therapy: Past, Present and Perspectives

International Nuclear Information System (INIS)

Jones, D.T.L

1999-01-01

Fast neutron therapy began as long ago as 1938 and subsequently proton, alpha particle, heavy ion, pion and neutron capture therapy have been used. To date it is estimated that in excess of 45000 people have undergone some form of hadron therapy. In the future it is expected that fast neutron therapy will be used for selected tumour types for which neutron are known to show improved cure rates. The future trends in charged particle therapy will be driven by increasing commercialization. The future of neutron capture therapy will depend on current clinical trials with epithermal neutron beams and the development of new tumour-seeking drugs

Radical Radiation Therapy After Lung-Sparing Surgery for Malignant Pleural Mesothelioma: Survival, Pattern of Failure, and Prognostic Factors

Energy Technology Data Exchange (ETDEWEB)

Minatel, Emilio [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Trovo, Marco, E-mail: marcotrovo33@hotmail.com [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Bearz, Alessandra [Department of Medical Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Di Maso, Matteo [Unit of Epidemiology and Biostatistics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Baresic, Tania [Department of Nuclear Medicine, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Drigo, Annalisa; Barresi, Loredana [Department of Medical Physics, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Furlan, Carlo [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Del Conte, Alessandro [Department of Medical Oncology, Pordenone General Hospital, Pordenone (Italy); Bruschi, Gioia [Department of Pneumology, Pordenone General Hospital, Pordenone (Italy); Fontana, Paolo [Department of Thoracic Surgery, Mestre General Hospital, Mestre (Italy); Pagan, Vittore [Department of Surgery, Centro di Riferimento Oncologico of Aviano, Aviano (Italy); Franchin, Giovanni [Department of Radiation Oncology, Centro di Riferimento Oncologico of Aviano, Aviano (Italy)

2015-11-01

Purpose: To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. Methods and Materials: The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura for diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Results: The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Conclusions: Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and

Feminist Identity Development: Implications for Feminist Therapy with Women.

Science.gov (United States)

McNamara, Kathleen; Rickard, Kathryn M.

1989-01-01

Discusses implications of the Downing and Roush (1985) feminist identity development model for feminist therapy with women. Describes potential pitfalls of feminist therapy and emergent issues at subsequent stages of client's identity development. Proposes research agenda for hypothesis testing of model when applied to therapy with women clients.…

Nerve agent intoxication: Recent neuropathophysiological findings and subsequent impact on medical management prospects

International Nuclear Information System (INIS)

Collombet, Jean-Marc

2011-01-01

This manuscript provides a survey of research findings catered to the development of effective countermeasures against nerve agent poisoning over the past decade. New neuropathophysiological distinctive features as regards organophosphate (OP) intoxication are presented. Such leading neuropathophysiological features include recent data on nerve agent-induced neuropathology, related peripheral or central nervous system inflammation and subsequent angiogenesis process. Hence, leading countermeasures against OP exposure are down-listed in terms of pre-treatment, protection or decontamination and emergency treatments. The final chapter focuses on the description of the self-repair attempt encountered in lesioned rodent brains, up to 3 months after soman poisoning. Indeed, an increased proliferation of neuronal progenitors was recently observed in injured brains of mice subjected to soman exposure. Subsequently, the latter experienced a neuronal regeneration in damaged brain regions such as the hippocampus and amygdala. The positive effect of a cytokine treatment on the neuronal regeneration and subsequent cognitive behavioral recovery are also discussed in this review. For the first time, brain cell therapy and neuronal regeneration are considered as a valuable contribution towards delayed treatment against OP intoxication. To date, efficient delayed treatment was lacking in the therapeutic resources administered to patients contaminated by nerve agents. - Highlights: → This review focuses on neuropathophysiology following nerve agent poisoning in mice. → Extensive data on long-term neuropathology and related inflammation are provided here. → Delayed self-repair attempts encountered in lesioned rodent brains are also described. → Cell therapy is considered as a valuable treatment against nerve agent intoxication.

Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response.

Science.gov (United States)

Nora, Tommi; Heinonen, Hanna; Tenhunen, Mirja; Rainesalo, Sirpa; Järvenpää, Soila; Lehtimäki, Kai; Peltola, Jukka

2018-01-01

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient's seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

Consecutive successful pregnancies subsequent to intravenous immunoglobulin therapy in a patient with recurrent spontaneous miscarriage

Directory of Open Access Journals (Sweden)

Diejomaoh MF

2015-12-01

Full Text Available Michael F Diejomaoh,1,2 Zainab Bello,2 Waleed Al Jassar,1,2 Jiri Jirous,2 Kavitha Karunakaran,2 Asiya T Mohammed11Department of Obstetrics and Gynaecology, Faculty of Medicine, Kuwait University, Safat, 2Maternity Hospital, Shuwaikh, Kuwait Background: Recurrent spontaneous miscarriage (RSM has a multifactorial etiology, mainly due to karyotype abnormalities including balanced translocation, anatomical uterine disorders, and immunological factors, although in 50%–60% the etiology is unexplained. The treatment of RSM remains challenging, and the role of intravenous immunoglobulin (IVIG in RSM is controversial. Case report: Mrs HM, 37 years old, obstetric summary: P0+1+13+1, a known case of hypothyroidism/polycystic ovary syndrome, married to an unrelated 47-year-old man, presented to our RSM clinic in early January 2014 for investigation and treatment. She has had multiple failed in vitro fertilization trials and 13 first-trimester missed miscarriages terminating at 6–7 weeks, all without IVIG therapy. Her tenth pregnancy was spontaneous, managed in London, UK, with multiple supportive therapy and courses of IVIG starting from the third to the 30th week of pregnancy. The pregnancy ended at 36 weeks of gestation with a cesarean section and a live girl baby was delivered. Mrs HM had balanced translocation, 46XX t (7:11 (p10:q10. Preimplantation genetic diagnosis/intracytoplasmic sperm injection/in vitro fertilization was performed with embryo transfer on May 29, 2014, and resulted in a successful pregnancy. She was commenced immediately on metformin, luteal support, and IVIG therapy, started at 6 weeks of gestation and at monthly intervals until 30 weeks of gestation, and also received additional therapy. The pregnancy was monitored with ultrasound, progressed uneventfully until admission at 35 weeks of gestation, with mildly elevated liver enzymes and suspected fetal growth restriction. She was managed conservatively, and in the light of

Treatment of Stage IV Non-small Cell Lung Cancer

Science.gov (United States)

Evans, Tracey; Gettinger, Scott; Hensing, Thomas A.; VanDam Sequist, Lecia; Ireland, Belinda; Stinchcombe, Thomas E.

2013-01-01

Background: Stage IV non-small cell lung cancer (NSCLC) is a treatable, but not curable, clinical entity in patients given the diagnosis at a time when their performance status (PS) remains good. Methods: A systematic literature review was performed to update the previous edition of the American College of Chest Physicians Lung Cancer Guidelines. Results: The use of pemetrexed should be restricted to patients with nonsquamous histology. Similarly, bevacizumab in combination with chemotherapy (and as continuation maintenance) should be restricted to patients with nonsquamous histology and an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1; however, the data now suggest it is safe to use in those patients with treated and controlled brain metastases. Data at this time are insufficient regarding the safety of bevacizumab in patients receiving therapeutic anticoagulation who have an ECOG PS of 2. The role of cetuximab added to chemotherapy remains uncertain and its routine use cannot be recommended. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as first-line therapy are the recommended treatment of those patients identified as having an EGFR mutation. The use of maintenance therapy with either pemetrexed or erlotinib should be considered after four cycles of first-line therapy in those patients without evidence of disease progression. The use of second- and third-line therapy in stage IV NSCLC is recommended in those patients retaining a good PS; however, the benefit of therapy beyond the third-line setting has not been demonstrated. In the elderly and in patients with a poor PS, the use of two-drug, platinum-based regimens is preferred. Palliative care should be initiated early in the course of therapy for stage IV NSCLC. Conclusions: Significant advances continue to be made, and the treatment of stage IV NSCLC has become nuanced and specific for particular histologic subtypes and clinical patient characteristics and according to the

Rapid-onset diabetic ketoacidosis secondary to nivolumab therapy

Directory of Open Access Journals (Sweden)

Senhong Lee

2018-04-01

Full Text Available We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non–small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home. He subsequently has developed likely autoimmune thyroiditis and autoimmune encephalitis.

Stimulation Induced Electrographic Seizures in Deep Brain Stimulation of the Anterior Nucleus of the Thalamus Do Not Preclude a Subsequent Favorable Treatment Response

Directory of Open Access Journals (Sweden)

Tommi Nora

2018-02-01

Full Text Available Deep brain stimulation (DBS of the anterior nucleus of the thalamus (ANT is a method of neuromodulation used for refractory focal epilepsy. We report a patient suffering from drug-resistant epilepsy who developed novel visual symptoms and atypical seizures with the onset of ANT-DBS therapy. Rechallenge under video electroencephalography recording confirmed that lowering the stimulation voltage alleviated these symptoms. Subsequent stimulation with the initial voltage value did not cause the recurrence of either the visual symptoms or the new seizure type, and appeared to alleviate the patient’s seizures in long-term follow-up. We therefore hypothesize that the occurrence of stimulation induced seizures at the onset of DBS therapy should not be considered as a failure in the DBS therapy, and the possibility of a subsequent favorable response to the treatment still exists.

Rational Emotive Behavior Therapy: Origins, Constructs, and Applications.

Science.gov (United States)

Watson, Joshua C.

In 1956, Dr. Albert Ellis presented his seminal work on Rational Therapy, subsequently renamed Rational Emotive Behavior Therapy (REBT) in 1993. This paper explores the origins, theoretical foundations, applications, and implications of REBT and provides a look at the empirical research available in support of the approach's efficacy. REBT is…

In vitro study on the schedule-dependency of the interaction between pemetrexed, gemcitabine and irradiation in non-small cell lung cancer and head and neck cancer cells

International Nuclear Information System (INIS)

Wouters, An; Pauwels, Bea; Lardon, Filip; Pattyn, Greet GO; Lambrechts, Hilde AJ; Baay, Marc; Meijnders, Paul; Vermorken, Jan B

2010-01-01

Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising. This in vitro study, for the first time, presents the triple combination of MTA, dFdC and irradiation using various treatment schedules. The cytotoxicity, radiosensitising potential and cell cycle effect of MTA were investigated in A549 (NSCLC) and CAL-27 (SCCHN) cells. Using simultaneous or sequential exposure schedules, the cytotoxicity and radiosensitising effect of 24 h MTA combined with 1 h or 24 h dFdC were analysed. Including a time interval between MTA exposure and irradiation seemed favourable to MTA immediately preceding or following radiotherapy. MTA induced a significant S phase accumulation that persisted for more than 8 h after drug removal. Among different MTA/dFdC combinations tested, the highest synergistic interaction was produced by 24 h MTA followed by 1 h dFdC. Combined with irradiation, this schedule showed a clear radiosensitising effect. Results from our in vitro model suggest that the sequence 24 h MTA → 1 h dFdC → RT is the most rational design and would, after confirmation in an in vivo setting, possibly provide the greatest benefit in the clinic

Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

Directory of Open Access Journals (Sweden)

Shimada M

2017-06-01

Full Text Available Midori Shimada,1,2 Minoru Fukuda,2,3 Masaaki Fukuda,2 Takeshi Kitazaki,2 Kohji Hashiguchi,2 Takaya Ikeda,1 Hiroyuki Yamaguchi,1 Katsumi Nakatomi,1 Kazuto Ashizawa,3 Hiroshi Mukae1 1Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 2Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan Abstract: A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks. Keywords: lung cancer, ALK, renal dysfunction, alectinib

Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants

NARCIS (Netherlands)

Lemmers, Petra M. A.; Toet, Mona C.; van Bel, Frank

OBJECTIVES. A hemodynamically important patent ductus arteriosus is a common problem in the first week of life in the preterm infant. Although patent ductus arteriosus induces alterations in organ perfusion, scarce information is available of the impact of patent ductus arteriosus and its subsequent

Recurrent hypoglycemia increases anxiety and amygdala norepinephrine release during subsequent hypoglycemia

Directory of Open Access Journals (Sweden)

Ewan eMcNay

2015-11-01

Full Text Available Recurrent hypoglycemia (RH is a common and debilitating side effect of therapy in patients with both type 1 and, increasingly, type 2 diabetes. Previous studies in rats have shown marked effects of RH on subsequent hippocampal behavioral, metabolic, and synaptic processes. In addition to impaired memory, patients experiencing RH report alterations in cognitive processes that include mood and anxiety, suggesting that RH may also affect amygdala function. We tested the impact of RH on amygdala function using an elevated plus-maze test of anxiety together with in vivo amygdala microdialysis for norepinephrine (NEp, a widely used marker of basolateral amygdala cognitive processes. In contrast to findings in the hippocampus and pre-frontal cortex, neither RH nor acute hypoglycemia alone significantly affected plus-maze performance or NEp release. However, animals tested when hypoglycemic who had previously experienced RH had elevated amygdala NEp during plus-maze testing, accompanied by increased anxiety (i.e. less time spent in the open arms of the plus-maze. The results show that RH has widespread effects on subsequent brain function, which vary by neural system.

Matching Subsequences in Trees

DEFF Research Database (Denmark)

Bille, Philip; Gørtz, Inge Li

2009-01-01

Given two rooted, labeled trees P and T the tree path subsequence problem is to determine which paths in P are subsequences of which paths in T. Here a path begins at the root and ends at a leaf. In this paper we propose this problem as a useful query primitive for XML data, and provide new...

Mindfulness and acceptance-based group therapy and traditional cognitive behavioral group therapy for social anxiety disorder: Mechanisms of change.

Science.gov (United States)

Kocovski, Nancy L; Fleming, Jan E; Hawley, Lance L; Ho, Moon-Ho Ringo; Antony, Martin M

2015-07-01

The present study investigated mechanisms of change for two group treatments for social anxiety disorder (SAD): cognitive behavioral group therapy (CBGT) and mindfulness and acceptance-based group therapy (MAGT). Participants were treatment completers (n = 37 for MAGT, n = 32 for CBGT) from a randomized clinical trial. Cognitive reappraisal was the hypothesized mechanism of change for CBGT. Mindfulness and acceptance were hypothesized mechanisms of change for MAGT. Latent difference score (LDS) analysis results demonstrate that cognitive reappraisal coupling (in which cognitive reappraisal is negatively associated with the subsequent rate of change in social anxiety) had a greater impact on social anxiety for CBGT than MAGT. The LDS bidirectional mindfulness model (mindfulness predicts subsequent change in social anxiety; social anxiety predicts subsequent change in mindfulness) was supported for both treatments. Results for acceptance were less clear. Cognitive reappraisal may be a more important mechanism of change for CBGT than MAGT, whereas mindfulness may be an important mechanism of change for both treatments. Copyright © 2015 Elsevier Ltd. All rights reserved.

The experience of adjusting to a diagnosis of non-epileptic attack disorder (NEAD) and the subsequent process of psychological therapy.

Science.gov (United States)

Wyatt, Caroline; Laraway, Alec; Weatherhead, Stephen

2014-10-01

Research suggests psychological therapy as the treatment of choice for individuals diagnosed with NEAD. This study explored the experience of adjusting to a diagnosis of NEAD and engagement with therapy through a qualitative methodology. Semi-structured interviews were conducted with 6 people with a diagnosis of NEAD and analysed using thematic analysis. Six master-themes were generated, with four discussed. Two themes were not discussed due to previous coverage in the literature and their less direct relevance to the service context. Theme 1: 'understanding NEAD' incorporated participants' evolving understanding of the diagnosis and their reflections on this. Theme 2: 'I can't deal with you' centres on participants' accounts of relationships with professionals in the context of NEAD. Theme 3: 'experiences of psychological therapy' reflected participants' experience of being referred to psychology and gaining a deeper understanding of themselves through therapy. Theme 4: 'adjusting to life with NEAD' explores participants' views on living with NEAD and their expectations for the future. This study extended previous research by highlighting the impact of how the diagnosis is received and understood on engagement in therapy. Improving awareness of NEAD amongst healthcare professionals is of key importance in reducing stigma and encouraging engagement in therapy. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Subsequence Automata with Default Transitions

DEFF Research Database (Denmark)

Bille, Philip; Gørtz, Inge Li; Skjoldjensen, Frederik Rye

2016-01-01

of states and transitions) of the subsequence automaton is O(nσ) and that this bound is asymptotically optimal. In this paper, we consider subsequence automata with default transitions, that is, special transitions to be taken only if none of the regular transitions match the current character, and which do...... not consume the current character. We show that with default transitions, much smaller subsequence automata are possible, and provide a full trade-off between the size of the automaton and the delay, i.e., the maximum number of consecutive default transitions followed before consuming a character......(nσ) and delay O(1), thus matching the bound for the standard subsequence automaton construction. The key component of our result is a novel hierarchical automata construction of independent interest....

Surgical Outcome of Intermittent Exotropia With Improvement in Control Grade Subsequent to Part-time Preoperative Occlusion Therapy.

Science.gov (United States)

Bang, Seung Pil; Lee, Dong Cheol; Lee, Se Youp

2018-01-01

To evaluate the effect of improvement in the control grade of intermittent exotropia using part-time occlusion therapy on the final postoperative outcome. Control of intermittent exotropia was graded as good, fair, or poor in 89 consecutive patients with intermittent exotropia during their first visit. The patients were reevaluated after part-time preoperative occlusion therapy and divided into two groups (improvement and no improvement) according to whether they showed improvement in control grade. The surgical success rate was compared retrospectively between the two groups. The mean angle of deviation on the first visit was 27.61 ± 5.40 prism diopters (PD) at distance and 29.82 ± 5.28 PD at near. There were significant improvements in the angles of deviation for distance (26.17 ± 5.09 PD) and near (27.26 ± 5.56 PD) after part-time occlusion (both P Part-time occlusion therapy improves the control grade of intermittent exotropia, leading to a better likelihood of successful surgery and a reduction of the angles of deviation for distance and near. [J Pediatr Ophthalmol Strabismus. 2018;55(1):59-64.]. Copyright 2017, SLACK Incorporated.

Mindfulness-based cognitive therapy for seasonal affective disorder : A pilot study

NARCIS (Netherlands)

Fleer, Joke; Schroevers, Maya; Panjer, Vera; Geerts, Erwin; Meesters, Ybe

2014-01-01

Background: The best available treatment for seasonal affective disorder (SAD) is light therapy. Yet, this treatment does not prevent recurrence of depression in subsequent seasons. The aim of the study is to gain preliminary insight in the efficacy of Mindfulness Based Cognitive Therapy (MBCT) in

Subsequence automata with default transitions

DEFF Research Database (Denmark)

Bille, Philip; Gørtz, Inge Li; Skjoldjensen, Frederik Rye

2017-01-01

of states and transitions) of the subsequence automaton is O(nσ) and that this bound is asymptotically optimal. In this paper, we consider subsequence automata with default transitions, that is, special transitions to be taken only if none of the regular transitions match the current character, and which do...... not consume the current character. We show that with default transitions, much smaller subsequence automata are possible, and provide a full trade-off between the size of the automaton and the delay, i.e., the maximum number of consecutive default transitions followed before consuming a character......(1), thus matching the bound for the standard subsequence automaton construction. Finally, we generalize the result to multiple strings. The key component of our result is a novel hierarchical automata construction of independent interest....

Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS

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Jeong Eun Kim

2018-04-01

Full Text Available Pemetrexed and platinum (PP combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM. However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions. We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found.

Mutational Profiling of Malignant Mesothelioma Revealed Potential Therapeutic Targets in EGFR and NRAS.

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Kim, Jeong Eun; Kim, Deokhoon; Hong, Yong Sang; Kim, Kyu-Pyo; Yoon, Young Kwang; Lee, Dae Ho; Kim, Sang-We; Chun, Sung-Min; Jang, Se Jin; Kim, Tae Won

2018-04-01

Pemetrexed and platinum (PP) combination chemotherapy is the current standard first-line therapy for treatment of malignant mesothelioma (MM). However, a useful predictive biomarker for PP therapy is yet to be found. Here, we performed targeted exome sequencing to profile somatic mutations and copy number variations in 12 MM patients treated with PP therapy. We identified 187 somatic mutations in 12 patients (65 synonymous, 102 missense, 2 nonsense, 5 splice site, and 13 small coding insertions/deletions). We identified somatic mutations in 23 genes including BAP1, TP53, NRAS, and EGFR. Interestingly, rare NRAS p.Q61K and EGFR exon 19 deletions were observed in 2 patients. We also found somatic chromosomal copy number deletions in CDKN2A and CDKN2B genes. Genetic alteration related to response after PP therapy was not found. Somatic mutation profiling in MM patients receiving PP therapy revealed genetic alterations in potential therapeutic targets such as NRAS and EGFR. No alterations in genes with potential predictive role for PP therapy were found. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

[Contract focused short-term group therapy--results of an evaluation].

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Hirschberg, Rainer; Meyer, Birgit

2010-01-01

A short description outlines the development of commission focused short-term therapy (AFoG) for children and adolescents. Subsequently the generic principles of psychotherapy are applied to AFoG in order to underline the basic assumptions of this variation of systemic group therapy. Behavioural changes arising in different contexts (school, family, group therapy) show the need for an appropriate flexibility of group therapy techniques. The evaluation was accomplished using the Child Behaviour Checklist (CBCL 4-18) at the beginning and 3 month after the end of the group therapy. The results show positive effects which finally are discussed critically.

Current treatments for advanced stage non-small cell lung cancer.

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Stinchcombe, Thomas E; Socinski, Mark A

2009-04-15

progressed on first-line therapy there are three agents available (docetaxel, pemetrexed, and erlotinib), but the efficacy of pemetrexed appears to be limited to patients with nonsquamous histology. Despite the improvements in care and number of therapeutic agents available, the survival for patients with advanced-stage NSCLC remains modest; novel approaches are required and participation in clinical trials should be encouraged.

Risks of subsequent contralateral fractures of the trochanteric region in elderly.

Science.gov (United States)

Pogliacomi, Francesco; Pellegrini, Andrea; Tacci, Fabrizio; Pedrini, Martina Francesca; Costantino, Cosimo; Pedrazzini, Alessio; Pedrazzi, Giuseppe; Lauretani, Fulvio; Vaienti, Enrico; Ceccarelli, Francesco

2017-01-16

Fractures in elderly are always a dramatic event and the healing is often not complete. In a context of bone fragility, repeated fractures are a growing problem in the industrialized world, in which the mean age of population is increasing. The aim of this study was to identify those general factors which may increase the risk of subsequent trochanteric fractures after an initial lesion. Three-hundred and thirty-one patients who underwent intramedullary fixation for trochanteric fractures between January 2012 and December 2013 were studied. Forty subjects yet alive (group 1), affected by a subsequent contralateral hip fracture, were compared with 202 patients (group 2) affected by isolated trochanteric fracture. Days of hospitalization before surgery, hospitalization, period of rehabilitation, type of discharge and comorbidities, that are reported in literature as possible risk factors for hip refracture, were analyzed. In addition, all patients were interviewed in order to assess if a therapy for osteoporosis was prescribed after the initial fracture and how their gait had been modified by fractures. Days of hospitalization before surgery, hospitalization, period of rehabilitation and type of discharge were not predictive factors for subsequent fractures, as well as diabetes mellitus, hypertension and cardiac diseases. The presence of neurologic and respiratory diseases were associated to a higher risk of refractures, as well as the absence of specific medical treatment for osteoporosis. Neurologic and respiratory comorbidities and the absence of osteoporosis medical treatment are the variables associated to a higher risk of contralateral fractures. Physicians can do more in terms of prevention and strategies must consider these risk factors.

Intravenous Fluid Therapy Course for the Licensed Practical Nurse. Instructor Guide.

Science.gov (United States)

Missouri Univ., Columbia. Instructional Materials Lab.

This curriculum guide provides materials for a 10-unit intravenous (IV) therapy course for licensed practical nurses. Units contain from one to nine lessons. The first unit provides an introduction and orientation to the course. Subsequent units concern documentation, anatomy and physiology as applied to IV therapy, fundamental aspects of fluid…

Mesothelioma - A rare cause of dysphagia

Directory of Open Access Journals (Sweden)

Vishwanathan Swati

2016-08-01

Full Text Available A 81-year-old elderly Caucasian male presented with progressive dysphagia and unintentional weight loss over four months. His history was significant for asbestos exposure; however there was no history of asbestos related lung disease. Barium swallow showed achalasia and a subsequent CT chest showed a posterior mediastinal mass 11.8×9.1×5.8cm, compressing the distal oesophagus. Laparoscopic biopsy of the mass showed an epitheloid mesothelioma. Mass was deemed unresectable and patient was started on chemotherapy with Cisplatin/Pemetrexed. Localised mesothelioma is extremely rare, and dysphagia can be uncommon presenting feature. 7.4 per cent of cases of Pseudoachalasia are attributed to mesothelioma

Potential efficacy of therapies targeting intrahepatic lesions after sorafenib treatment of patients with hepatocellular carcinoma

International Nuclear Information System (INIS)

Terashima, Takeshi; Yamashita, Tatsuya; Horii, Rika; Arai, Kuniaki; Kawaguchi, Kazunori; Kitamura, Kazuya; Yamashita, Taro; Sakai, Yoshio; Mizukoshi, Eishiro; Honda, Masao; Kaneko, Shuichi

2016-01-01

We investigated the contribution of subsequent therapy for advanced hepatocellular carcinoma refractory or intolerant to sorafenib. Further, we investigated the impact of sorafenib on overall survival using individual data. We reviewed the medical records of patients with advanced hepatocellular carcinoma treated with sorafenib. Survival after sorafenib treatment and overall survival were defined as the time when we discovered that patients were either refractory or intolerant to sorafenib and the period from the start of sorafenib treatment, respectively, until death during the study. We compared patients’ prognoses according to their subsequent treatment as follows: group A, therapies targeting intrahepatic lesions; group B, systemic therapies alone; group C, no subsequent therapy. We used linear regression analysis to determine whether there was an association with survival after sorafenib treatment and with overall survival. Of 79 patients, 63 (79.7 %) received one or more subsequent therapies (44 and 19 patients in groups A and B, respectively). The five patients who survived more than two years after sorafenib treatment was discontinued responded to therapies targeting intrahepatic lesions. The median survival times of groups A, B, and C were 11.9 months, 5.8 months, and 3.6 months, respectively. Multivariate analysis revealed that group A, Child-Pugh score, serum α-fetoprotein level, and cause of failure of sorafenib treatment were independent prognostic factors for survival after sorafenib treatment. Individual survival after sorafenib treatment correlated highly with overall survival. Targeting intrahepatic lesions may be useful for treating patients with advanced hepatocellular carcinoma patients after sorafenib treatment is discontinued. The online version of this article (doi:10.1186/s12885-016-2380-4) contains supplementary material, which is available to authorized users

The time course of subsequent hospitalizations and associated costs in survivors of an ischemic stroke in Canada

OpenAIRE

Ishak Khajak J; Migliaccio-Walle Kristen; Caro J Jaime; Proskorovsky Irina; O'Brien Judith A

2006-01-01

Abstract Background Documentation of the hospitalizations rates following a stroke provides the inputs required for planning health services and to evaluate the economic efficiency of any new therapies. Methods Hospitalization rates by cause were examined using administrative data on 18,695 patients diagnosed with ischemic stroke (first or subsequent, excluding transient ischemic attack) in Saskatchewan, Canada between 1990 and 1995. Medical history was available retrospectively to January 19...

TH-302, a hypoxia-activated prodrug with broad in vivo preclinical combination therapy efficacy: optimization of dosing regimens and schedules.

Science.gov (United States)

Liu, Qian; Sun, Jessica D; Wang, Jingli; Ahluwalia, Dharmendra; Baker, Amanda F; Cranmer, Lee D; Ferraro, Damien; Wang, Yan; Duan, Jian-Xin; Ammons, W Steve; Curd, John G; Matteucci, Mark D; Hart, Charles P

2012-06-01

Subregional hypoxia is a common feature of tumors and is recognized as a limiting factor for the success of radiotherapy and chemotherapy. TH-302, a hypoxia-activated prodrug selectively targeting hypoxic regions of solid tumors, delivers a cytotoxic warhead to the tumor, while maintaining relatively low systemic toxicity. The antitumor activity, different dosing sequences, and dosing regimens of TH-302 in combination with commonly used conventional chemotherapeutics were investigated in human tumor xenograft models. Seven chemotherapeutic drugs (docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide) were tested in combination with TH-302 in eleven human xenograft models, including non-small cell lung cancer (NSCLC), colon cancer, prostate cancer, fibrosarcoma, melanoma, and pancreatic cancer. The antitumor activity of docetaxel, cisplatin, pemetrexed, irinotecan, doxorubicin, gemcitabine, and temozolomide was increased when combined with TH-302 in nine out of eleven models tested. Administration of TH-302 2-8 h prior to the other chemotherapeutics yielded superior efficacy versus other sequences tested. Simultaneous administration of TH-302 and chemotherapeutics increased toxicity versus schedules with dosing separations. In a dosing optimization study, TH-302 administered daily at 50 mg/kg intraperitoneally for 5 days per week in the H460 NSCLC model showed the optimal response with minimal toxicity. TH-302 enhances the activity of a wide range of conventional anti-neoplastic agents in a broad panel of in vivo xenograft models. These data highlight in vivo effects of schedule and order of drug administration in regimen efficacy and toxicity and have relevance to the design of human regimens incorporating TH-302.

Improvements in closeness, communication, and psychological distress mediate effects of couple therapy for veterans.

Science.gov (United States)

Doss, Brian D; Mitchell, Alexandra; Georgia, Emily J; Biesen, Judith N; Rowe, Lorelei Simpson

2015-04-01

Empirically based couple therapy results in significant improvements in relationship satisfaction for the average couple; however, further research is needed to identify mediators that lead to change and to ensure that improvements in mediators predict subsequent-not just concurrent-relationship satisfaction. In addition, given that much of the current literature on couple therapy examines outcomes in a research environment, it is important to examine mediators in a treatment-as-usual setting. To address these questions, 161 heterosexual couples (322 individuals) received treatment-as-usual couple therapy at one of two Veteran Administration Medical Centers (M = 5.0 and 13.0 sessions at the two sites) and were assessed before every session. The majority of couples were married (85%) and had been together for a median of 7.8 years (SD = 13). Participants were primarily White, non-Hispanic (69%), African American (21%), and White, Hispanic/Latino (8%). Individuals' own self-reported improvements in communication, emotional closeness, and psychological distress (but not frequency of behaviors targeted in treatment) mediated the effect of treatment on their subsequent relationship satisfaction. When all significant mediators were examined simultaneously, improvements in men's and women's emotional closeness and men's psychological distress independently mediated subsequent relationship satisfaction. In contrast, improvements in earlier relationship satisfaction mediated the effect of treatment only on subsequent psychological distress. This study identifies unique mediators of treatment effects and shows that gains in mechanisms predict subsequent relationship satisfaction. Future investigations should focus on the role of emotional closeness and psychological distress-constructs that have often been neglected-in couple therapy. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Addiction between therapy and criminalization.

Science.gov (United States)

Birklbauer, Alois; Schmidthuber, Kathrin

2014-12-01

The present paper delves into the question of whether and to what extent it is appropriate to leave addiction problems between the conflicting priorities of therapy and criminalization. After outlining the issue the criminal addictive behaviour including crimes associated with drug misuse and with obtaining drugs is described. Subsequently it is discussed if and how you could make allowances for addiction-related legal insanity in the criminal law sector. Following a few remarks on the principle of "voluntary therapy instead of penal sanction" as a way to alleviate the strict law on narcotic drugs misuse a summary and an outlook with criminal-political demands complete the issue.

Kinetic therapy improves oxygenation in critically ill pediatric patients.

Science.gov (United States)

Schultz, Theresa Ryan; Lin, Richard; Francis, Barbara A; Hales, Roberta L; Colborn, Shawn; Napoli, Linda A; Helfaer, Mark A

2005-07-01

To compare changes in oxygenation after manual turning and percussion (standard therapy) and after automated rotation and percussion (kinetic therapy). Randomized crossover trial. General and cardiac pediatric intensive care units. Intubated and mechanically ventilated pediatric patients who had an arterial catheter and no contraindications to using a PediDyne bed. Patients were placed on a PediDyne bed (Kinetic Concepts) and received 18 hrs blocks of standard and kinetic therapy in an order determined by randomization. Arterial blood gases were measured every 2 hrs during each phase of therapy. Oxygenation index and arterial-alveolar oxygen tension difference [P(A-a)O(2)] were calculated. Indexes calculated at baseline and after each 18-hr phase of therapy were analyzed. Fifty patients were enrolled. Data from 15 patients were either not collected or not used due to reasons that included violation of protocol and inability to tolerate the therapies in the study. Indexes of oxygenation were not normally distributed and were compared using Wilcoxon signed rank testing. Both therapies led to improvements in oxygenation, but only those from kinetic therapy achieved statistical significance. In patients receiving kinetic therapy first, median oxygenation index decreased from 7.4 to 6.19 (p = .015). The median P(A-a)O(2) decreased from 165.2 to 126.4 (p = .023). There were continued improvements in oxygenation after the subsequent period of standard therapy, with the median oxygenation index decreasing to 5.52 and median P(A-a)O(2) decreasing to 116.0, but these changes were not significant (p = .365 and .121, respectively). When standard therapy was first, the median oxygenation index decreased from 8.83 to 8.71 and the median P(a-a)o(2) decreased from 195.4 to 186.6. Neither change was significant. Median oxygenation index after the subsequent period of kinetic therapy was significantly lower (7.91, p = .044) and median P(A-a)O(2) trended lower (143.4, p = .077

Annual review of advances in lung cancer clinical research: a report for the year 2009.

Science.gov (United States)

Stinchcombe, Thomas E; Bogart, Jeffrey; Wigle, Dennis A; Govindan, Ramaswamy

2010-07-01

The use of positron emission tomography compared with conventional staging increases the detection of extrathoracic metastases and reduces the number futile thoracotomies in patients being evaluated for surgical resection. Long-term follow-up of one of the two adjuvant chemotherapy trials revealed a continued overall survival (OS) benefit to adjuvant chemotherapy. In locally advanced non-small cell lung cancer, a phase III trial of chemoradiotherapy alone and with surgical resection revealed no statistically significant difference in OS between the treatment arms. In advanced stage non-small cell lung cancer, a phase III trial compared gefitinib with carboplatin and paclitaxel in a clinically enriched patient population for epidermal growth factor receptor (EGFR) tyrosine kinase (TK) mutations; among patients with an EGFR TK mutation, patients in gefitinib arm compared with carboplatin and paclitaxel arm experienced a statistically significant superior response rate and progression-free survival, and among patients without EGFR TK mutation patients in the gefitinib arm compared with carboplatin and paclitaxel experienced a statistically significant inferior response rate and progression-free survival. A phase III trial of platinum-based therapy with and without cetuximab in the first-line setting revealed improved OS in the cetuximab arm. A phase III trial of maintenance pemetrexed compared with placebo in patients who had not progressed after initial platinum-based therapy revealed an improvement in OS of patients in the pemetrexed arm with nonsquamous histology. In limited-stage small cell lung cancer, a phase III trial compared standard and high-dose prophylactic cranial irradiation and revealed no significant difference in the rate of brain metastases between the two treatment arms.

Ethical reasoning and informed consent in occupational therapy.

Science.gov (United States)

Kyler-Hutchison, P

1988-05-01

Two major ethical theories, the teleological and the deontological, are defined and briefly discussed. A subsequent discussion explores how the ethical principles of informed consent and patient autonomy operate in medical decisions. The application to occupational therapy is left for the reader's judgment.

Advances in diagnosis and treatment of malignant pleural mesothelioma

Directory of Open Access Journals (Sweden)

Giorgio Vittorio Scagliotti

2011-12-01

Full Text Available Malignant pleural mesothelioma (MPM is an aggressive but relatively rare malignancy with median survival ranging from 8 to 14 months depending on stage and presentation of disease. New diagnostic procedures are urgently needed, selecting patients in earlier stages to evaluate therapeutic approaches which combine chemotherapy, surgery and radiotherapy. Combination chemotherapy represents the only resource available for advanced disease.The combination of cisplatin and pemetrexed is the treatment of choice. This review summarizes the latest developments in diagnostic techniques and the available therapeutic options for the management of MPM. Particular attention is given to the molecular basis of biologically targeted therapies to be used in the future.

Chronic gingivitis: the prevalence of periodontopathogens and therapy efficiency.

Science.gov (United States)

Igic, M; Kesic, L; Lekovic, V; Apostolovic, M; Mihailovic, D; Kostadinovic, L; Milasin, J

2012-08-01

The purpose of this study was to determine the level of gingival inflammation and the prevalence of periodontopathogenic microorganisms in adolescents with chronic gingivitis, as well as to compare the effectiveness of two approaches in gingivitis treatment-basic therapy alone and basic therapy + adjunctive low-level laser therapy (LLLT). After periodontal evaluation, the content of gingival pockets of 140 adolescents with gingivitis was analyzed by multiplex PCR for the presence of P. gingivalis, A. actinomycetemcomitans, T. forsythensis and P. intermedia. Subsequent to bacteria detection, the examinees were divided into two groups with homogenous clinical and microbiological characteristics. Group A was subjected to basic gingivitis therapy, and group B underwent basic therapy along with adjunctive LLLT. A statistically significant difference between the values of plaque-index (PI) and sulcus bleeding index (SBI) before and after therapy was confirmed in both groups (pgingivitis should be regarded as a sign for dentists to foster more effective oral health programs. LLLT appears to be beneficial as adjuvant to basic therapy.

A Review of Subsequence Time Series Clustering

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Seyedjamal Zolhavarieh

2014-01-01

Full Text Available Clustering of subsequence time series remains an open issue in time series clustering. Subsequence time series clustering is used in different fields, such as e-commerce, outlier detection, speech recognition, biological systems, DNA recognition, and text mining. One of the useful fields in the domain of subsequence time series clustering is pattern recognition. To improve this field, a sequence of time series data is used. This paper reviews some definitions and backgrounds related to subsequence time series clustering. The categorization of the literature reviews is divided into three groups: preproof, interproof, and postproof period. Moreover, various state-of-the-art approaches in performing subsequence time series clustering are discussed under each of the following categories. The strengths and weaknesses of the employed methods are evaluated as potential issues for future studies.

A review of subsequence time series clustering.

Science.gov (United States)

Zolhavarieh, Seyedjamal; Aghabozorgi, Saeed; Teh, Ying Wah

2014-01-01

Clustering of subsequence time series remains an open issue in time series clustering. Subsequence time series clustering is used in different fields, such as e-commerce, outlier detection, speech recognition, biological systems, DNA recognition, and text mining. One of the useful fields in the domain of subsequence time series clustering is pattern recognition. To improve this field, a sequence of time series data is used. This paper reviews some definitions and backgrounds related to subsequence time series clustering. The categorization of the literature reviews is divided into three groups: preproof, interproof, and postproof period. Moreover, various state-of-the-art approaches in performing subsequence time series clustering are discussed under each of the following categories. The strengths and weaknesses of the employed methods are evaluated as potential issues for future studies.

A Review of Subsequence Time Series Clustering

Science.gov (United States)

Teh, Ying Wah

2014-01-01

Clustering of subsequence time series remains an open issue in time series clustering. Subsequence time series clustering is used in different fields, such as e-commerce, outlier detection, speech recognition, biological systems, DNA recognition, and text mining. One of the useful fields in the domain of subsequence time series clustering is pattern recognition. To improve this field, a sequence of time series data is used. This paper reviews some definitions and backgrounds related to subsequence time series clustering. The categorization of the literature reviews is divided into three groups: preproof, interproof, and postproof period. Moreover, various state-of-the-art approaches in performing subsequence time series clustering are discussed under each of the following categories. The strengths and weaknesses of the employed methods are evaluated as potential issues for future studies. PMID:25140332

Tinnitus retraining therapy.

Science.gov (United States)

Jastreboff, P J

2007-01-01

Tinnitus retraining therapy (TRT) is a specific clinical method based on the neurophysiological model of tinnitus described by Jastreboff (Jastreboff, P.J. (1990). Neurosci. Res., 8: 221-254). The method is aimed at habituation of reactions evoked by tinnitus, and subsequently habituation of the tinnitus perception. Several other methods have been suggested for habituation of tinnitus, but in TRT two components that strictly follow the principles of the neurophysiological model of tinnitus are implemented and necessary: (1) counseling, aimed at reclassification of tinnitus to a category of a neutral signals and (2) sound therapy, aimed at weakening tinnitus-related neuronal activity as suggested by Jastreboff and Hazell (Jastreboff, P.J. and Hazell, J.W.P. (2004). Cambridge University Press, Cambridge). This chapter outlines the theoretical basis of TRT as well as comments on the clinical outcome of the use of TRT for different kinds of tinnitus.

Köebner phenomenon induced by cupping therapy in a psoriasis patient.

Science.gov (United States)

Yu, Rui-Xing; Hui, Yun; Li, Cheng-Rang

2013-06-15

Psoriasis is a chronic, immune-mediated inflammatory and refractory disease. The koebner phenomenon, which can be induced by trauma, is common in psoriasis patients. Herein, we report a patient with psoriasis who was treated by cupping therapy and subsequently developed the koebner phenomenon (KP) at the cupped sites. To our knowledge, it is the first report about cupping therapy leading to KP in a psoriasis patient.

Subsequent investigation and management of patients with intermediate-category and - probability ventilation - perfusion scintigraphy

International Nuclear Information System (INIS)

Walsh, G.; Jones, D.N.

2000-01-01

The authors wished to determine the proportion of patients with intermediate-category and intermediate-probability ventilation-perfusion scintigraphy (IVQS) who proceed to further imaging for investigation of thromboembolism, to identify the defining clinical parameters and to determine the proportion of patients who have a definite imaging diagnosis of thromboembolism prior to discharge from hospital on anticoagulation therapy. One hundred and twelve VQS studies performed at the Flinders Medical Centre over a 9-month period were reported as having intermediate category and probability for pulmonary embolism. Medical case notes were available for review in 99 of these patients and from these the pretest clinical probability, subsequent patient progress and treatment were recorded. Eight cases were excluded because they were already receiving anticoagulation therapy. In the remaining 91 patients the pretest clinical probability was considered to be low in 25; intermediate in 30; and high in 36 cases. In total, 51.6% (n = 47) of these patients (8% (n = 2) with low, 66% (n = 20) with intermediate, and 69.4% (n = 25) with high pretest probability) proceeded to CT pulmonary angiography (CTPA) and/or lower limb duplex Doppler ultrasound (DUS) evaluation. Of the patients with IVQS results, 30.7% (n 28) were evaluated with CTPA. No patient with a low, all patients with a high and 46% of patients with an intermediate pretest probability initially received anticoagulation therapy. This was discontinued in three patients with high and in 12 patients with intermediate clinical probability prior to discharge from hospital. Overall, 40% of patients discharged on anticoagulation therapy (including 39% of those with a high pretest probability) had a positive imaging diagnosis of thromboembolism The results suggest that, although the majority of patients with intermediate-to-high pretest probability and IVQS proceed to further imaging investigation, CTPA is relatively underused in

CEO age and gender: Subsequent market performance

Directory of Open Access Journals (Sweden)

Marcelo Eduardo

2016-12-01

Full Text Available The issue of CEO age and gender vs. concurrent performance is extensively examined, but the association with subsequent performance has limited treatment in the financial literature, and with conflicting findings. In the current study, we examine the association between CEO age and gender, and subsequent company market performance using a more recent set of observations and the standard four-factor model to estimate future cumulative abnormal shareholder returns. We find that subsequent abnormal shareholder returns are marginally significantly higher for female CEOs than for their male counterparts, but no material pattern is observed between CEO age and subsequent abnormal shareholder return performance.

Study on subsequent neurologic complications in children with acute leukemia

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Naoaki; Shimazaki, Haruyo; Hoshi, Yasutaka; Akatsuka, Jun-ichi (Jikei Univ., Tokyo (Japan). School of Medicine)

1989-06-01

Twenty-seven children with acute leukemia were studied in order to detect the subsequent neurologic complications due to chemotherapy and radiation therapy. Twenty-four patients with ALL received central nervous system prophylaxis including cranial irradiation. The methods of evaluation consisted of electroencephalogram (EEG), computed tomography of the head (CT scan), soft neurological sign, intelligence quotient (IQ) and Bender Gestalt test. The patients with relapse showed severe abnormalities in various kinds of examinations. Younger children at diagnosis were associated with a higher abnormality rate of soft neurological signs and Bender Gestalt test. Factors which were found to be closely associated with a lower IQ score included younger children at diagnosis and longer duration of remission time. These results indicate the need for caution for the dosage of cranial irradiation for younger patients in CNS prophylaxis, and improvement of a lower IQ score in long-term survivors requires further investigation as to the appropriate intellectual environment for their development after remission. (author).

Experimental Simulation of the Effects of an Initial Antibiotic Treatment on a Subsequent Treatment after Initial Therapy Failure

NARCIS (Netherlands)

Feng, Yanfang; Händel, Nadine; de Groot, Marnix H. P.; Brul, Stanley; Schultsz, Constance; ter Kuile, Benno H.

2014-01-01

Therapy failure of empirical antibiotic treatments prescribed by primary care physicians occurs commonly. The effect of such a treatment on the susceptibility to second line antimicrobial drugs is unknown. Resistance to amoxicillin was rapidly induced or selected in E. coli at concentrations

Wildland fire limits subsequent fire occurrence

Science.gov (United States)

Sean A. Parks; Carol Miller; Lisa M. Holsinger; Scott Baggett; Benjamin J. Bird

2016-01-01

Several aspects of wildland fire are moderated by site- and landscape-level vegetation changes caused by previous fire, thereby creating a dynamic where one fire exerts a regulatory control on subsequent fire. For example, wildland fire has been shown to regulate the size and severity of subsequent fire. However, wildland fire has the potential to influence...

Targeting eukaryotic translation in mesothelioma cells with an eIF4E-specific antisense oligonucleotide.

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Blake A Jacobson

Full Text Available BACKGROUND: Aberrant cap-dependent translation is implicated in tumorigenesis in multiple tumor types including mesothelioma. In this study, disabling the eIF4F complex by targeting eIF4E with eIF4E-specific antisense oligonucleotide (4EASO is assessed as a therapy for mesothelioma. METHODS: Mesothelioma cells were transfected with 4EASO, designed to target eIF4E mRNA, or mismatch-ASO control. Cell survival was measured in mesothelioma treated with 4EASO alone or combined with either gemcitabine or pemetrexed. Levels of eIF4E, ODC, Bcl-2 and β-actin were assessed following treatment. Binding to a synthetic cap-analogue was used to study the strength of eIF4F complex activation following treatment. RESULTS: eIF4E level and the formation of eIF4F cap-complex decreased in response to 4EASO, but not mismatch control ASO, resulting in cleavage of PARP indicating apoptosis. 4EASO treatment resulted in dose dependent decrease in eIF4E levels, which corresponded to cytotoxicity of mesothelioma cells. 4EASO resulted in decreased levels of eIF4E in non-malignant LP9 cells, but this did not correspond to increased cytotoxicity. Proteins thought to be regulated by cap-dependent translation, Bcl-2 and ODC, were decreased upon treatment with 4EASO. Combination therapy of 4EASO with pemetrexed or gemcitabine further reduced cell number. CONCLUSION: 4EASO is a novel drug that causes apoptosis and selectively reduces eIF4E levels, eIF4F complex formation, and proliferation of mesothelioma cells. eIF4E knockdown results in decreased expression of anti-apoptotic and pro-growth proteins and enhances chemosensitivity.

29 CFR 18.407 - Subsequent remedial measures.

Science.gov (United States)

2010-07-01

... OFFICE OF ADMINISTRATIVE LAW JUDGES Rules of Evidence Relevancy and Its Limits § 18.407 Subsequent... event less likely to occur, evidence of the subsequent measures is not admissible to prove negligence or...

Combined miglustat and enzyme replacement therapy in two patients with type 1 Gaucher disease: two case reports.

Science.gov (United States)

Amato, Dominick; Patterson, Mary Anne

2018-01-27

Intravenous enzyme replacement therapy is a first-line therapy for Gaucher disease type 1, and substrate reduction therapy represents an oral treatment alternative. Both enzyme replacement therapy and substrate reduction therapy are generally used as monotherapies in Gaucher disease. However, one randomized study and several case reports have described combination therapy over short time periods. We report two female Gaucher disease type 1 patients of mainly Anglo-Saxon descent, where combined enzyme replacement therapy and miglustat substrate reduction therapy were administered to overcome refractory clinical symptoms. The first patient was diagnosed at age 17 and developed Gaucher disease-related bone manifestations that worsened despite starting imiglucerase enzyme replacement therapy. After switching to miglustat substrate reduction therapy, her bone symptoms improved, but she developed tremors and eventually switched back to enzyme replacement therapy. Miglustat was later recommenced in combination with ongoing enzyme replacement therapy due to continued bone pain, and her bone symptoms improved along with maintained visceral manifestations. Enzyme replacement therapy was subsequently tapered off and the patient has since been successfully maintained on miglustat. The second patient was diagnosed aged 3, and commenced imiglucerase enzyme replacement therapy aged 15. After 9 years on enzyme replacement therapy she switched to miglustat substrate reduction therapy and her core symptoms were maintained/stable for 3 years. Imiglucerase enzyme replacement therapy was later added as a boost to therapy and her symptoms were subsequently maintained over a 2.3-year period. However, miglustat was discontinued due to her relocation, necessitating an increase in enzyme replacement therapy dose. Overall, both patients benefited from combination therapy. While the majority of Gaucher disease type 1 patients will not need treatment with both substrate reduction therapy

TARGETED RADIOFREQUENCY THERAPY FOR TRAINING INDUCED MUSCLE FATIGUE EFFECTIVE OR NOT

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Ondrej Prouza

2016-12-01

Full Text Available Background: Training induced muscle fatigue (hereinafter also referred as TIMF is leading to unwanted consequences among sportsmen and actively sporting people such as decreased muscle strength and additional painful discomfort and mobility issues. The knowledge about the mechanisms of influencing the fatigue induced processes in muscle tissue is not comprehensive. The conventional manual techniques, cold patches and conventional physiotherapy have some effect in improving these conditions, however, finding effective methods to influence these consequences appears beneficial in sports medicine. Such method could be Radiofrequency therapy up to 0.5 MHz, known as Targeted Radiofrequency Therapy (hereinafter also referred as TR-Therapy. Aim of this self-controlled study is to evaluate the effect of the TR-Therapy for over-exertion management including the effect on decreased muscle strength, limited range of motion and possible painful discomfort. Materials: 7 healthy and actively sporting participants underwent through 2 stages (Active stage – including overexertion of the forearm flexors and subsequent TR-Therapy session; and Control stage - including overexertion of the forearm flexors and subsequent resting period. Data for muscle strength in kg, active Range of Motion (ROM in (º and Pain and discomfort perception by 10 point Visual Analog Scale (VAS were obtained and evaluated. Results: 31% increase in the muscle strength during the active stage was observed and respectively 12% during the control stage, with level of significance p0.05. Conclusions: The results of this study suggest TR-Therapy as effective solution for muscle strength restoration after TIMF.

Rational emotive behavior therapy: applications for working with parents and teachers

OpenAIRE

Terjesen,Mark D.; Kurasaki,Robyn

2009-01-01

Given the high rates of reported emotional stress among parents and teachers, the Rational Emotive Behavior Therapy approach appears to be a useful strategy to promote more effective parent and teacher emotional functioning and increase child positive behaviors and learning. The Rational Emotive Behavior Therapy model may be helpful for clinicians who work with the parents and the family by identifying and subsequently changing their unhealthy ideas, enhancing emotional functioning, and incre...

Behaviour therapy for obesity treatment considering approved drug therapy

Directory of Open Access Journals (Sweden)

Wasem, Jürgen

2008-05-01

interventions of media alone as well as through the intervention of media in conjunction with personal support within the groups. However, analyses of the inter-group comparisons offer no statistically significant difference. However, analyses of the inter-group comparisons offer no statistically significant difference. Comparative analyses confirm the effectiveness of behaviour therapy in combination with additional drug treatment when compared to behaviour therapy alone.In all the studies presented here, relevant changes in weight of -5% to -10% are only partially achieved. High weight losses of less than -10% were found among the intervention group in two of the studies. One study reported a weight loss of -11.4% with the “group therapy” intervention method, while another study reported a weight loss of -11.2% with the “behaviour therapy plus drug treatment” intervention method. Studies with a subsequent follow-up period indicate a clear weight loss at the end of the intervention followed by a renewed weight gain towards the end of the follow-up period.For the evaluation of economic, social-ethical or legal aspects we could not identify any studies. Discussion: A comparative assessment among the studies proved difficult due to their heterogeneous nature. Little conformity can be detected in either the contents of the behaviour therapy or in the treatment plans. The length of the follow-up periods also varies from study to study. Many studies only analyze weight changes within one group or for the entire study population. However, the results of these analyses all indicate a significant weight loss at the end of the intervention. Conclusion: Some effects of behaviour therapy on a reduction in weight can be shown. However, relevant weight changes of -5% to -10% are only achieved to a certain extent. The extremely heterogeneous nature of the interventions makes a comparison of the study results very difficult. A trend can be detected indicates that those treatments

Primary Occipital Ewing's Sarcoma with Subsequent Spinal Seeding.

Science.gov (United States)

Alqahtani, Ali; Amer, Roaa; Bakhsh, Eman

2017-01-01

Ewing's sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing's sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT) imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) seeding from the L5 to the S4 vertebrae. Primary cranial Ewing's sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing's sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing's sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

Leuconostoc garlicum: an unusual pathogen in the era of vancomycin therapy.

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Kumar, Anil; Augustine, Deepthi; Mehta, Asmita; Dinesh, Kavitha R; Viswam, Darsana; Philip, Rosamma

2012-01-01

Leuconostoc garlicum, belonging to the family of Leuconostocaceae, is a catalase-negative, Gram-positive ovoid cocci, intrinsically resistant to vancomycin. Clinical infection by Leuconostoc garlicum is rare. We report a case of respiratory tract infection subsequent to vancomycin therapy.

A study on subsequent neurologic complications in children with acute leukemia

International Nuclear Information System (INIS)

Kobayashi, Naoaki; Shimazaki, Haruyo; Hoshi, Yasutaka; Akatsuka, Jun-ichi

1989-01-01

Twenty-seven children with acute leukemia were studied in order to detect the subsequent neurologic complications due to chemotherapy and radiation therapy. Twenty-four patients with ALL received central nervous system prophylaxis including cranial irradiation. The methods of evaluation consisted of electroencephalogram (EEG), computed tomography of the head (CT scan), soft neurological sign, intelligence quotient (IQ) and Bender Gestalt test. The patients with relapse showed severe abnormalities in various kinds of examinations. Younger children at diagnosis were associated with a higher abnormality rate of soft neurological signs and Bender Gestalt test. Factors which were found to be closely associated with a lower IQ score included younger children at diagnosis and longer duration of remission time. These results indicate the need for caution for the dosage of cranial irradiation for younger patients in CNS prophylaxis, and improvement of a lower IQ score in long-term survivors requires further investigation as to the appropriate intellectual environment for their development after remission. (author)

Radionuclide therapy practice and facilities in Europe

International Nuclear Information System (INIS)

Hoefnagel, C.A.; Clarke, S.E.M.; Fischer, M.; Chatal, J.F.; Lewington, V.J.; Nilsson, S.; Troncone, L.; Vieira, M.R.

1999-01-01

Using a questionnaire the EANM Task Group Radionuclide Therapy in 1993 collected data on the current practice of radionuclide therapy in European countries. Subsequently, at the request of the EANM Executive Committee, the EANM Radionuclide Therapy Committee has made an inventory of the distribution of facilities for radionuclide therapy and undertaken an assessment of the total number of patients treated throughout Europe and of the types of treatment provides, with the aim of supporting the development of policy to adjust the available capacity to the needs by the year 2000. For this purpose, a second, more detailed questionnaire was sent out the members and national advisors of the Committee (see below), who gathered the data for each country that was a member of the EANM at the time. It is concluded that a wide bariation in therapy practice exists across Europe, particularly in the utilisation of radionuclide therapy, the requirement and availability of proper isolation facilities and the background training of those undertaking therapy. More uniform guidelines and legislation are required, although changes in legislation may have a significant impact in some countries. Although there is wide variation in the therapies used in each country, one the whole it appears that there is an underutilisation of nuclear medicine as a therapeutic modality. A rapidly increasing role may be expected, in particular for oncological indications requiring high-dose radionuclide treatment. Therefore there is an urgent need for a greater number of isolation beds in dedicated centers throughout Europe

Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results.

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Gurudu, S R; Griffel, L H; Gialanella, R J; Das, K M

1999-09-01

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.

Quality of life assessment in radionuclide therapy: a feasibility study of the EORTC QLQ-C30 questionnaire in palliative 131I-lipiodol therapy

International Nuclear Information System (INIS)

Brans, B.; Lambert, B.; De Beule, E.; De Winter, F.; Dierckx, R.A.; Van Belle, S.; Van Vlierberghe, H.; De Hemptinne, B.

2002-01-01

The good tolerance of radionuclide therapy has frequently been proposed as a major advantage. This study explored the feasibility of using the EORTC QLQ-C30 questionnaire in palliative iodine-131 lipiodol therapy for hepatocellular carcinoma. Questionnaires were completed during interviews in which all symptoms, co-morbidity and medication were assessed at baseline within 1 week before 131 I-lipiodol therapy, and subsequently after 1 and 3 months, in 20 patients treated with locoregional, intra-arterial 131 I-lipiodol therapy with or without cisplatin. Principal observations were that (1) a number of important scales, i.e. overall quality of life, physical functioning and pain, worsened between 0 and 3 months after 131 I-lipiodol therapy, irrespective of tumour response, and (2) the occurrence of clinical side-effects was associated with a negative impact on quality of life and physical functioning 1 and 3 months after 131 I-lipiodol. The QLQ-C30 can be regarded as a feasible method for quality of life assessment in 131 I-lipiodol therapy for hepatocellular carcinoma and possibly in other radionuclide therapies. These observations should be related to the impact of other treatment modalities on quality of life. (orig.)

Subsequent pregnancy outcome after previous foetal death

NARCIS (Netherlands)

Nijkamp, J. W.; Korteweg, F. J.; Holm, J. P.; Timmer, A.; Erwich, J. J. H. M.; van Pampus, M. G.

Objective: A history of foetal death is a risk factor for complications and foetal death in subsequent pregnancies as most previous risk factors remain present and an underlying cause of death may recur. The purpose of this study was to evaluate subsequent pregnancy outcome after foetal death and to

Preoperative gemcitabine-based chemoradiation therapy for resectable pancreatic cancer

International Nuclear Information System (INIS)

Takahashi, Hidenori; Ohigashi, Hiroaki; Goto, Kunihito; Marubashi, Shigeru; Yano, Masahiko; Ishikawa, Osamu

2013-01-01

During the period from 2002 to 2011, a total of 240 consecutive patients with resectable pancreatic cancer received preoperative chemoradiation therapy (CRT). Among 240 patients, 201 patients underwent the subsequent pancreatectomy (resection rate: 84%). The 5-year overall survival of resected cases was 56% and the median survival of 39 unresected cases was 11 months. The 5-year locoregional recurrence rate of resected cases was 15%. The 5-year overall survival of the entire cohort (n=240) was 47%. The preoperative CRT and subsequent pancreatectomy provided a favorable surgical result, which was contributed by several characteristics of preoperative CRT: the prominent locoregional treatment effect with lower incidence of locoregional recurrence, and the discrimination between patients who are likely to benefit from subsequent surgery and those who are not. (author)

Tritium sorption by cement and subsequent release

International Nuclear Information System (INIS)

Ono, F.; Tanaka, S.; Yamawaki, M.

1994-01-01

In a fusion reactor or tritium handling facilities, contamination of concrete by tritium and subsequent release from it to the reactor or experimental rooms is a matter of problem for safety control of tritium and management of operational environment. In order to evaluate these tritium behavior, interaction of tritiated water with concrete or cement should be clarified. In the present study, HTO sorption and subsequent release from cement were studied by combining various experimental methods. From the basic studies on tritium-cement interactions, it has become possible to evaluate tritium uptake by cement or concrete and subsequent tritium release behavior as well as tritium removing methods from them

Updates in the diagnosis and treatment of malignant pleural mesothelioma.

Science.gov (United States)

Katzman, Daniel; Sterman, Daniel H

2018-03-16

This review article describes current diagnostic and treatment modalities for malignant pleural mesothelioma (MPM). Few randomized trials in MPM have demonstrated improved survival with current therapies. A randomized trial of first-line chemotherapy with and without bevacizumab in unresectable MPM is the only randomized trial of a new treatment regimen to demonstrate a survival benefit since cisplatin with pemetrexed became the standard of care for unresectable MPM in 2003. Unfortunately, in unresectable MPM, first-line chemotherapy alone or in combination with bevacizumab has demonstrated only limited improvements in overall survival. Recently, in nonrandomized observational studies, multimodality treatments with chemotherapy, surgery, radiation, and novel therapies have been associated with prolonged survival in select patients. Currently, there are no FDA approved second-line therapies, and clinical trial enrollment is recommended for second-line treatment. MPM remains difficult to treat and has an overall poor prognosis despite current multimodality treatment. Thoracoscopy with multiple pleural biopsies can provide adequate tissue specimens for diagnostic testing to distinguish histologic MPM subtypes and perform molecular profiling, which influence prognosis and treatment options. In early clinical trials, immunotherapies and therapies directed against cancer-associated antigens and oncogenic alterations are emerging as promising future treatments.

Unusual progression and subsequent improvement in cystic lung disease in a child with radiation-induced lung injury

Energy Technology Data Exchange (ETDEWEB)

Wolf, Michael S. [Monroe Carell Jr. Children' s Hospital at Vanderbilt, Department of Pediatrics, Nashville, TN (United States); Chadha, Ashley D. [Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Department of Pediatrics, Nashville, TN (United States); Carroll, Clinton M.; Borinstein, Scott C. [Vanderbilt University School of Medicine, Division of Hematology and Oncology, Department of Pediatrics, Nashville, TN (United States); Young, Lisa R. [Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Department of Pediatrics, Nashville, TN (United States); Vanderbilt University School of Medicine, Division of Allergy, Pulmonary and Critical Care, Department of Medicine, Nashville, TN (United States); Vanderbilt University School of Medicine, Division of Pulmonary Medicine, Nashville, TN (United States)

2015-07-15

Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. (orig.)

Pasireotide therapy in a rare and unusual case of plurihormonal pituitary macroadenoma.

Science.gov (United States)

Rajendran, Rajesh; Naik, Sarita; Sandeman, Derek D; Nasruddin, Azraai B

2013-01-01

We report the use of pasireotide in a rare and unusual case of pituitary macroadenoma co-secreting GH, prolactin and ACTH. A 62-year-old Caucasian man presented with impotence. Clinically, he appeared acromegalic and subsequent investigations confirmed GH excess and hyperprolactinaemia. Magnetic resonance imaging (MRI) of pituitary revealed a large pituitary macroadenoma. He underwent trans-sphenoidal surgery and histology confirmed an adenoma with immunohistochemistry positive for ACTH, GH and prolactin. Acromegaly was not cured following surgery and inadequately controlled despite subsequent octreotide therapy. He underwent further debulking pituitary surgery, following which IGF1 levels improved but still high. This time adenoma cells showed immunohistochemistry positivity for ACTH only, following which subsequent investigations confirmed intermittent hypercortisolaemia compatible with pituitary Cushing's disease. We recommended radiotherapy, but in view of the pluripotential nature of the tumour, we proceeded with a trial of s.c. pasireotide therapy on the basis that it may control both his acromegaly and Cushing's disease. After 3 months of pasireotide therapy, his mean GH and IGF1 levels improved significantly, with improvement in his symptoms but intermittent hypercortisolaemia persists. His glycaemic control deteriorated requiring addition of new anti-diabetic medication. MRI imaging showed loss of contrast uptake within the tumour following pasireotide therapy but no change in size. We conclude that our patient has had a partial response to pasireotide therapy. Long-term follow-up studies are needed to establish its safety and efficacy in patients with acromegaly and/or Cushing's disease. Plurihormonal pituitary adenomas are rare and unusual.Patients with pituitary adenomas co-secreting ACTH and GH are more likely to present with acromegaly because GH excess can mask hypercortisolaemia.Pasireotide holds potential where conventional somatostatin analogues

Rocuronium-sugammadex use for electroconvulsive therapy in a hemodialysis patient: a case report

OpenAIRE

Kurita, Shigeaki; Moriwaki, Katsuyuki; Shiroyama, Kazuhisa; Sanuki, Mikako; Toyota, Yukari; Takebayashi, Minoru

2016-01-01

Background Recently, rocuronium with subsequent use of sugammadex was proposed for electroconvulsive therapy (ECT) as an alternative to succinylcholine. Because sugammadex is cleared via the kidney with no metabolism, it is unknown that rocuronium-sugammadex use is safe in hemodialysis patients who received ECT. Case presentation In this case report, we used rocuronium with subsequent administration of sugammadex in a 69-year-old female, hemodialysis patient, scheduled for ten ECT sessions fo...

Tinnitus Retraining Therapy (TRT) as a method for treatment of tinnitus and hyperacusis patients.

Science.gov (United States)

Jastreboff, P J; Jastreboff, M M

2000-03-01

The aim of this paper is to provide information about the neurophysiologic model of tinnitus and Tinnitus Retraining Therapy (TRT). With this overview of the model and therapy, professionals may discern with this basic foundation of knowledge whether they wish to pursue learning and subsequently implement TRT in their practice. This paper provides an overview only and is insufficient for the implementation of TRT.

An adult case of temporomandibular joint osteoarthritis treated with splint therapy and the subsequent orthodontic occlusal reconstruction

Directory of Open Access Journals (Sweden)

Hanefi Kurt

2011-01-01

Full Text Available Herein we report treatment for a 19-year-old female patient with severe osteoarthritis of the temporomandibular joint. The patient had severe open bite with a Class II molar relationship. She had limited mouth opening and pain. Clinical examination and magnetic resonance imaging revealed that she had anterior disc displacement without reduction. By splint therapy, limited mouth opening and pain was eliminated, but an anterior open bite developed after the treatment. By orthodontic treatment, an acceptable occlusion was achieved with a Class I molar relationship.

Intravenous immunoglobulin therapy leading to dramatic improvement in a patient with systemic juvenile idiopathic arthritis and severe pericarditis resistant to steroid pulse therapy.

Science.gov (United States)

Aizawa-Yashiro, Tomomi; Oki, Eishin; Tsuruga, Kazushi; Nakahata, Tohru; Ito, Etsuro; Tanaka, Hiroshi

2012-05-01

A 7-year-old Japanese boy with a 4-month history of systemic juvenile idiopathic arthritis (s-JIA) experienced disease flare with spiking fever, exanthema and arthralgia. He then developed progressive dyspnea due to severe pericarditis, and proinflammatory hypercytokinemia was suspected. Methylprednisolone pulse therapy was ineffective and echocardiography showed massive pericardial effusion had persisted. Alternatively, subsequent intravenous immunoglobulin (IVIG) therapy resulted in dramatic resolution of the pericardial effusion, and his general condition significantly improved within a few days. This case report may lend further support the use of IVIG for selected patients with s-JIA and severe pericarditis.

SUBSEQUENTLY AQCUIRED ASSETS AS FIDUCIARY SECURITY ON BANK LOANS

Directory of Open Access Journals (Sweden)

Trisadini Prasastinah Usanti

2016-05-01

Full Text Available Collateral in terms of subsequently acquired assets namely subsequently acquired credit might be charged with fiduciary security. This collateral is not considered ideal regarding the high risk a bank must take. To minimize the risks, the bank analyzes the credit thoroughly, impose fiduciary security officials perfectly and performs monitoring of credits regularly to avoid misconduct committed by the debtor. If a default occurs, the bank will take over the assets. Nevertheless, the problems of execution on the subsequently acquired credits might arise due to debtor’s default and bad debts to the third party. Consequently, subsequently acquired assets as collateral provides as additional collateral. Keywords: bank, subsequently acquired objects, fiduciary, security, loans.

Development of Extracorporeal Shock Wave Therapy for the Treatment for Ischemic Cardiovascular Diseases

Science.gov (United States)

Shimokawa, Hiroaki

Cardiovascular diseases, such as coronary artery disease and peripheral artery disease, are the major causes of death in developed countries, and the number of elderly patients has been rapidly increasing worldwide. Thus, it is crucial to develop new non-invasive therapeutic strategies for these patients. We found that a low-energy shock wave (SW) (about 10% of the energy density that is used for urolithiasis) effectively increases the expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. Subsequently, we demonstrated that extracorporeal cardiac SW therapy with low-energy SW up-regulates the expression of VEGF, enhances angiogenesis, and improves myocardial ischemia in a pig model of chronic myocardial ischemia without any adverse effects in vivo. Based on these promising results in animal studies, we have subsequently developed a new, non-invasive angiogenic therapy with low-energy SW for cardiovascular diseases. Our extracorporeal cardiac SW therapy improved symptoms and myocardial perfusion evaluated with stress-scintigraphy in patients with severe coronary artery disease without indication of percutaneous coronary intervention or coronary artery bypass surgery. Importantly, no procedural complications or adverse effects were noted. The SW therapy was also effective in ameliorating left ventricular remodeling after acute myocardial infarction in pigs and in enhancing angiogenesis in hindlimb ischemia in animals and patients with coronary artery disease. Furthermore, our recent experimental studies suggest that the SW therapy is also effective for indications other than cardiovascular diseases. Thus, our extracorporeal cardiac SW therapy is an effective, safe, and non-invasive angiogenic strategy for cardiovascular medicine.

Non-small cell lung cancer: RT out, pembrolizumab in, and vaccine hope or hype

Directory of Open Access Journals (Sweden)

Robbins RA

2016-11-01

Full Text Available No abstract available. Article truncated at 150 words. Three articles on non-small cell lung cancer (NSCLC recently appeared which were of interest and might alter therapy. The first on whole brain radiation therapy (WBRT was presented at the at the European Respiratory Society (ERS International Congress 2016 and simultaneously published online in the Lancet (1. WBRT and dexamethasone have been the standard of care for patients with NSCLC brain metastases. However, the study of 538 randomized patients concludes that WBRT provides "little additional clinically significant benefit" with brain metastases. Notably, all the patients were unsuitable for surgical resection or stereotactic radiotherapy, owing to widespread metastases. However, patients younger than 60 years did seem to have a survival advantage and might represent an exception. The second study presented at the European Society for Medical Oncology (ESMO 2016 Congress reports that the addition of pembrolizumab to first-line treatment with pemetrexed and carboplatin significantly improved objective response rate and progression-free survival ...

Bell's palsy and choreiform movements during peginterferon α and ribavirin therapy

Institute of Scientific and Technical Information of China (English)

Sener Barut; Hatice Karaer; Erol Oksuz; Asl Gündodu Eken; Ayse Nazl Basak

2009-01-01

Neuropsychiatric side effects of long-term recombinant interferon-α therapy consist of a large spectrum of symptoms. In the literature, cranial neuropathy, especially Bell's palsy, and movement disorders, have been reported much less often than other neurotoxic effects. We report a case of Bell's palsy in a patient with chronic hepatitis C during peginterferon-α and ribavirin therapy. The patient subsequently developed clinically inapparent facial nerve involvement on the contralateral side and showed an increase in choreic movements related to Huntington's disease during treatment.

Comparison of semiquantitative fluorescence imaging and PET tracer uptake in mesothelioma models as a monitoring system for growth and therapeutic effects

International Nuclear Information System (INIS)

Saito, Yuriko; Furukawa, Takako; Arano, Yasushi; Fujibayashi, Yasuhisa; Saga, Tsuneo

2008-01-01

Introduction: Various techniques are available for in vivo imaging, and precise understanding of their characteristics is essential for effective use of the imaging results. We established human mesothelioma cell lines expressing red fluorescent protein (RFP) and examined their fluorescence intensity and uptake of positron emission tomography (PET) tracer analogs to compare their characteristics and assess their usefulness in the evaluation of therapeutics. Method: A human mesothelioma cell line was stably transfected to express RFP. Fluorescence, cell number and protein amount were measured during cell growth and treatment with cytotoxic reagents. In in vivo experiments, RFP-expressing cells were injected subcutaneously or into the pleural cavity of nude mice, and fluorescence images were taken with or without pemetrexed treatment. The uptake of [ 3 H]3'-deoxy-3'-fluorothymidine ([ 3 H]FLT) and [ 14 C]2-fluoro-2-deoxy-D-glucose ([ 14 C]FDG) under treatment with the above reagents in vitro and in vivo were examined. Results: Strong correlation was observed between fluorescence intensity and total cell number with or without cytotoxic treatment. The uptake of [ 3 H]FLT and [ 14 C]FDG decreased rapidly after the initiation of treatment with actinomycin D or cycloheximide. When treated with pemetrexed, the uptake of [ 3 H]FLT temporarily increased. The cells formed subcutaneous and orthotopic tumors, with fluorescence intensity correlating with tumor volume. The correlation was sustained under pemetrexed treatment. The uptake of [ 3 H]FLT in vivo increased significantly early after pemetrexed treatment. Conclusion: Fluorescence imaging could be used to semiquantitatively monitor tumor size, whereas PET could be used to monitor tumor response to therapeutic treatments, and especially, FLT might be a good marker of the response to anti-folate chemotherapeutics

Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

Science.gov (United States)

Sengbusch, Evan R.

Physical properties of proton interactions in matter give them a theoretical advantage over photons in radiation therapy for cancer treatment, but they are seldom used relative to photons. The primary barriers to wider acceptance of proton therapy are the technical feasibility, size, and price of proton therapy systems. Several aspects of the proton therapy landscape are investigated, and new techniques for treatment planning, optimization, and beam delivery are presented. The results of these investigations suggest a means by which proton therapy can be delivered more efficiently, effectively, and to a much larger proportion of eligible patients. An analysis of the existing proton therapy market was performed. Personal interviews with over 30 radiation oncology leaders were conducted with regard to the current and future use of proton therapy. In addition, global proton therapy market projections are presented. The results of these investigations serve as motivation and guidance for the subsequent development of treatment system designs and treatment planning, optimization, and beam delivery methods. A major factor impacting the size and cost of proton treatment systems is the maximum energy of the accelerator. Historically, 250 MeV has been the accepted value, but there is minimal quantitative evidence in the literature that supports this standard. A retrospective study of 100 patients is presented that quantifies the maximum proton kinetic energy requirements for cancer treatment, and the impact of those results with regard to treatment system size, cost, and neutron production is discussed. This study is subsequently expanded to include 100 cranial stereotactic radiosurgery (SRS) patients, and the results are discussed in the context of a proposed dedicated proton SRS treatment system. Finally, novel proton therapy optimization and delivery techniques are presented. Algorithms are developed that optimize treatment plans over beam angle, spot size, spot spacing

Emerging therapies in multiple myeloma.

Science.gov (United States)

El-Amm, Joelle; Tabbara, Imad A

2015-06-01

The treatment of multiple myeloma has evolved significantly over the past 2 decades due to the use of high-dose chemotherapy and autologous stem cell transplantation, and the subsequent introduction of the immunomodulatory agents (thalidomide and lenalidomide) and the proteasome inhibitor (bortezomib). The median overall survival of multiple myeloma patients has increased significantly with patients younger than age 50 years experiencing a 10-year survival rate of around 40%. However, despite the increased effectiveness of the first-line agents, the majority of patients will eventually relapse and become drug resistant. Promising novel therapies have recently emerged and are being used to treat relapsed and refractory patients. This review will cover the clinical data regarding these emergent therapies that include new generation of proteasome inhibitors (carfilzomib, ixazomib, oprozomib, and marizomib), immunomodulatory drugs (pomalidomide), monoclonal antibodies (elotuzumab and daratumumab), signal transduction modulator (perifosine), and histone deacetylase inhibitors (vorinostat and panobinostat).

Diagnosis and therapy of osteoporosis in geriatric trauma patients: an update

Directory of Open Access Journals (Sweden)

Schray Deborah

2016-12-01

Full Text Available Demographic changes confront clinicians with an increasing number of orthogeriatric patients. These patients present with comorbidities, which force their surgeons to take into consideration their medical condition. A major risk factor for fractures in orthogeriatric patients is osteoporosis in combination with frailty. To prevent subsequent fractures in these patients, we need to pay attention to adequate osteoporosis treatment in orthogeriatric patients. There is a huge treatment gap. In Germany, 77% of patients with osteoporosis are not treated adequately. Even after fragility fractures, a low percentage of patients receive a specific osteoporosis therapy. Secondary prevention is of great importance in the treatment of these patients. Diagnostics and treatment should be already initiated with the admission to the hospital. Treatment decisions need to be made individually based on the risk profile of the patients. After discharge, it is important to involve the patients’ general practitioners and to follow up on patients regularly to improve their compliance and to ensure adequate therapy. Establishing a fracture liaison service helps coordinating osteoporosis treatment during hospitalization and after discharge. Subsequent fractures can be reduced; therefore, it is an effective service for secondary prevention. The present article provides an overview of how an efficient identification and subsequent treatment of osteoporosis can be achieved in aged trauma patients.

Radiomic signature of infiltration in peritumoral edema predicts subsequent recurrence in glioblastoma: implications for personalized radiotherapy planning.

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Rathore, Saima; Akbari, Hamed; Doshi, Jimit; Shukla, Gaurav; Rozycki, Martin; Bilello, Michel; Lustig, Robert; Davatzikos, Christos

2018-04-01

Standard surgical resection of glioblastoma, mainly guided by the enhancement on postcontrast T1-weighted magnetic resonance imaging (MRI), disregards infiltrating tumor within the peritumoral edema region (ED). Subsequent radiotherapy typically delivers uniform radiation to peritumoral FLAIR-hyperintense regions, without attempting to target areas likely to be infiltrated more heavily. Noninvasive in vivo delineation of the areas of tumor infiltration and prediction of early recurrence in peritumoral ED could assist in targeted intensification of local therapies, thereby potentially delaying recurrence and prolonging survival. This paper presents a method for estimating peritumoral edema infiltration using radiomic signatures determined via machine learning methods, and tests it on 90 patients with de novo glioblastoma. The generalizability of the proposed predictive model was evaluated via cross-validation in a discovery cohort ([Formula: see text]) and was subsequently evaluated in a replication cohort ([Formula: see text]). Spatial maps representing the likelihood of tumor infiltration and future early recurrence were compared with regions of recurrence on postresection follow-up studies with pathology confirmation. The cross-validated accuracy of our predictive infiltration model on the discovery and replication cohorts was 87.51% (odds ratio = 10.22, sensitivity = 80.65, and specificity = 87.63) and 89.54% (odds ratio = 13.66, sensitivity = 97.06, and specificity = 76.73), respectively. The radiomic signature of the recurrent tumor region revealed higher vascularity and cellularity when compared with the nonrecurrent region. The proposed model shows evidence that multiparametric pattern analysis from clinical MRI sequences can assist in in vivo estimation of the spatial extent and pattern of tumor recurrence in peritumoral edema, which may guide supratotal resection and/or intensification of postoperative radiation therapy.

IMPACT STUDY: MK-0646 (DALOTUZUMAB, INSULIN GROWTH FACTOR 1 RECEPTOR (IGF-1R ANTIBODY COMBINED WITH PEMETREXED AND CISPLATIN IN STAGE IV METASTATIC NON-SQUAMOUS LUNG CANCER

Directory of Open Access Journals (Sweden)

Chao H Huang

2016-01-01

Full Text Available Background: Insulin-like growth factor 1 receptor (IGF-1R regulates cell growth, proliferation and apoptosis. Adenocarcinoma and never-smokers have a higher expression of IGF-1R, which is associated with worse overall survival. Dalotuzumab-MK0646 (D is a humanized monoclonal antibody that targets IGF-1R. Pemetrexed (P has higher activity in non-squamous lung cancer (NSQL. We initiated a randomized phase II trial to test the combination of P and Cisplatin (C +/- D in NSQL.Methods: Eligibility criteria: untreated NSQL stage IIIB or IV, ECOG 0 or 1, measurable disease, adequate renal, hepatic and hematologic function, and no other intercurrent illness. P at 500mg/m2 and C at 75mg/m2 IV were given every 3 weeks. D was given at 10mg/kg IV weekly on days 1, 8 and 15 of every 3-week cycle in the experimental group. The patients had a radiographic assessment after every 2 cycles and were treated for a maximum of 6 cycles if there was a response or stable disease. The primary objective of the study was to compare the clinical response rates of PC vs PC+D. Results: From 1/2009 to 2/2011, the study accrued 26 subjects: 16 male and 10 female, with a median age of 59; 14 were treated with PC and 12 were treated with PC+D. We observed 2 partial responses (PR, 7 stable disease (SD, 3 progressive disease (PD, and 2 were not evaluable (NE in the PC arm. In comparison, for the PC+D arm there were: 3 PR, 4 SD, 4 PD and 1 NE. The hematologic toxicity was similar in both groups. There higher incidence of hyperglycemia the experimental group; 4 cases with grade 3 and 1 case with grade 4. Conclusion: PC+D had a similar response rate compared to PC, with a higher rate of hyperglycemia. Identification of responders using predictive markers would be key to continuing the study of D in NSQL.

Eagle Syndrome: diagnostic imaging and therapy

International Nuclear Information System (INIS)

Nickel, J.; Andresen, R.; Sonnenburg, M.; Scheufler, O.

2004-01-01

In the case of clinical symptoms such as dysphagia, foreign-body sensation and chronic neck or facial pain close to the ear, an Eagle syndrome should be considered in the differential diagnosis. Rational diagnostics and therapy are elucidated on the basis of four case reports. Four patients presented in the out-patients clinic with chronic complaints on chewing and a foreign-body sensation in the tonsil region. Upon specific palpation below the mandibular angle, pain radiating into the ear region intensified. In all patients, local anaesthesia with lidocaine only led to a temporary remission of symptoms. Imaging diagnostics then performed initially included cranial survey radiograms according to Clementschitsch as well as in the lateral ray path and an OPTG. An axial spiral-CT was then performed using the thin-layer technique with subsequent 3-D reconstruction. Therapy consisted of elective resection with a lateral external incision from the retromandibular. From a symptomatic point of view, the cranial survey radiograms and the OPTG revealed hypertrophic styloid processes. The geometrically corrected addition of the axial CT images produced an absolute length of 51-58 mm. The 3-D reconstruction made it possible to visualise the exact spatial orientation of the styloid processes. An ossification of the stylohyoid ligament could definitely be ruled out on the basis of the imaging procedures. After resection of the megastyloid, the patients were completely free of symptoms. Spiral-CT with subsequent 3-D reconstruction is the method of choice for exact determination of the localisation and size of a megastyloid, while cranial survey radiograms according to Clementschitsch and in the lateral ray path or an OPTG can provide initial information. The therapy of choice is considered to be resection of the megastyloid, whereby an external lateral incision has proved effective. (orig.) [de

Induced abortion and subsequent pregnancy duration

DEFF Research Database (Denmark)

Zhou, Wei Jin; Sørensen, Henrik Toft; Olsen, Jørn

1999-01-01

OBJECTIVE: To examine whether induced abortion influences subsequent pregnancy duration. METHODS: Women who had their first pregnancies during 1980, 1981, and 1982 were identified in three Danish national registries. A total of 15,727 women whose pregnancies were terminated by first-trimester ind......OBJECTIVE: To examine whether induced abortion influences subsequent pregnancy duration. METHODS: Women who had their first pregnancies during 1980, 1981, and 1982 were identified in three Danish national registries. A total of 15,727 women whose pregnancies were terminated by first......-trimester induced abortions were compared with 46,026 whose pregnancies were not terminated by induced abortions. All subsequent pregnancies until 1994 were identified by register linkage. RESULTS: Preterm and post-term singleton live births were more frequent in women with one, two, or more previous induced...... abortions. After adjusting for potential confounders and stratifying by gravidity, the odds ratios of preterm singleton live births in women with one, two, or more previous induced abortions were 1.89 (95% confidence interval [CI] 1.70, 2.11), 2.66 (95% CI 2.09, 3.37), and 2.03 (95% CI 1.29, 3...

Challenges in economic modeling of anticancer therapies: an example of modeling the survival benefit of olaparib maintenance therapy for patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer.

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Hettle, Robert; Posnett, John; Borrill, John

2015-01-01

The aim of this paper is to describe a four health-state, semi-Markov model structure with health states defined by initiation of subsequent treatment, designed to make best possible use of the data available from a phase 2 clinical trial. The approach is illustrated using data from a sub-group of patients enrolled in a phase 2 clinical trial of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation (NCT00753545). A semi-Markov model was developed with four health states: progression-free survival (PFS), first subsequent treatment (FST), second subsequent treatment (SST), and death. Transition probabilities were estimated by fitting survival curves to trial data for time from randomization to FST, time from FST to SST, and time from SST to death. Survival projections generated by the model are broadly consistent with the outcomes observed in the clinical trial. However, limitations of the trial data (small sample size, immaturity of the PFS and overall survival [OS] end-points, and treatment switching) create uncertainty in estimates of survival. The model framework offers a promising approach to evaluating cost-effectiveness of a maintenance therapy for patients with cancer, which may be generalizable to other chronic diseases.

The role of maintenance pemetrexed in the treatment of non-small-cell lung cancer

OpenAIRE

Rafii, S

2010-01-01

Saeed Rafii, Michael H CullenDepartment of Medical Oncology, Queen Elizabeth Hospital, University Hospital Birmingham, Edgbaston, Birmingham, B15 2TH, United KingdomAbstract: Until recently, the weight of evidence has supported the discontinuation of ­chemotherapy in advanced non-small-cell lung cancer (NSCLC) after 4–6 cycles of induction therapy. This allows patients with limited life expectancy a “treatment holiday.” A minority of cases then go on to r...

38 CFR 36.4324 - Guaranty claims; subsequent accounting.

Science.gov (United States)

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Guaranty claims; subsequent accounting. 36.4324 Section 36.4324 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS... § 36.4324 Guaranty claims; subsequent accounting. (a) Subject to the limitation that the total amounts...

Medical nutrition therapy in chronic kidney disease; from dialysis to transplant: A case report

Directory of Open Access Journals (Sweden)

Gabriela Leal-Escobar

2016-01-01

Full Text Available Chronic kidney disease has direct implications in nutritional status, causing anorexia and muscular catabolism. These situations are frequent in kidney renal replacement therapy in which nutritional disorders and inflammatory mechanisms associated with therapy often lead to the development of protein-energy wasting. Nutrition therapy has shown an adequate therapeutic strategy to prevent and treat metabolic alterations, reducing surgical and nutritional complication risks in kidney transplantation patients. The current case reports nutritional intervention on a continuous ambulatory peritoneal dialysis patient who was subsequently prescribed to automatic peritoneal dialysis and, finally, kidney transplant from a living donor.

Helicobacter pylori eradication therapy: A review of current trends.

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Olokoba, A B; Obateru, O A; Bojuwoye, M O

2013-01-01

Helicobacter pylori has been implicated in the formation of chronic gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma and gastric cancer. Eradication of H. Pylori has been recommended as treatment and prevention for these complications. This review is based on a search of Medline, the Cochrane Database of Systemic Reviews, and citation lists of relevant publications. Subject heading and key words used include H. Pylori, current treatment and emerging therapy. Only articles in English were included. There has been a substantial decline in the H. pylori eradication rates over the years, despite the use of proton pump inhibitor and bismuth salts for triple and quadruple therapies respectively. The reasons for eradication failure are diverse, among them, antibiotic resistance is an important factor in the treatment failure. Primary resistance to clarithromycin or metronidazole significantly affects the efficacy of eradication therapy. This has led to the introduction of second line, third line "rescue," and sequential therapies for resistant cases. Subsequently, new antibiotic combinations with proton-pump inhibitors and bismuth salts are being studied in the last decade, to find out the antibiotics that are capable of increasing the eradication rates. Some of these antibiotics include Levofloxacin, Doxycycline, Rifaximin, Rifampicin, Furazolidone based therapies. Studies are ongoing to determine the efficacy of Lactoferrin based therapy.

Permutations avoiding an increasing number of length-increasing forbidden subsequences

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Elena Barcucci

2000-12-01

Full Text Available A permutation π is said to be τ-avoiding if it does not contain any subsequence having all the same pairwise comparisons as τ. This paper concerns the characterization and enumeration of permutations which avoid a set F j of subsequences increasing both in number and in length at the same time. Let F j be the set of subsequences of the form σ(j+1(j+2, σ being any permutation on {1,...,j}. For j=1 the only subsequence in F 1 is 123 and the 123-avoiding permutations are enumerated by the Catalan numbers; for j=2 the subsequences in F 2 are 1234 2134 and the (1234,2134 avoiding permutations are enumerated by the Schröder numbers; for each other value of j greater than 2 the subsequences in F j are j! and their length is (j+2 the permutations avoiding these j! subsequences are enumerated by a number sequence {a n } such that C n ≤ a n ≤ n!, C n being the n th Catalan number. For each j we determine the generating function of permutations avoiding the subsequences in F j according to the length, to the number of left minima and of non-inversions.

Subsequence Generation for the Airline Crew Pairing Problem

DEFF Research Database (Denmark)

Rasmussen, Matias Sevel; Lusby, Richard Martin; Ryan, David

of the solutions. The LP solutions from the subsequence generation approach are less fractional, but it comes at the cost of a worse solution quality. The approach in the present paper is novel. To our knowledge generation of subsequences have not been described and tested previously in the literature....

Breast-conserving therapy in patients with bilateral breast cancer: Do today's treatment choices burn bridges for tomorrow?

International Nuclear Information System (INIS)

Gilroy, Jeffrey S.; Morris, Christopher G.; Mendenhall, Nancy Price

2005-01-01

Purpose: To determine how often initial treatment choices limit treatment options for subsequent breast cancer management in patients undergoing breast-conserving therapy (BCT), in particular with treatment of internal mammary nodes. Methods and Materials: Between January 1985 and June 2001, 464 women with pathologic Stage 0, I, and II (T0-2, N0-1) breast cancer underwent BCT at our institution. All 464 patients had computed tomography-based treatment planning. In patients with bilateral breast cancer, the planning computed tomography scans were used to determine the impact initial radiation therapy fields had on treatment options for subsequent contralateral breast cancer. Results: There were 500 breast cancers diagnosed in 464 patients. Thirty-six patients (8%) had bilateral breast cancer with 9 (2%) synchronous and 27 (6%) metachronous primaries. In 80 patients, the ipsilateral internal mammary nodes were explicitly treated. Initial breast cancer treatment choices impacted subsequent treatment decisions for the contralateral breast in only 2 of 464 patients (0.4%) in the study: 2 of 80 patients (2.5%) whose internal mammary nodes were treated, and 2 of 27 patients (7.4%) who developed metachronous bilateral breast cancer. Conclusions: Initial BCT, including internal mammary node irradiation, rarely compromised future contralateral breast-conserving therapy

Atrial therapies reduce atrial arrhythmia burden in defibrillator patients.

Science.gov (United States)

Friedman, P A; Dijkman, B; Warman, E N; Xia, H A; Mehra, R; Stanton, M S; Hammill, S C

2001-08-28

Approximately 25% of patients who receive an implantable cardioverter-defibrillator (ICD) to treat ventricular tachyarrhythmias have documented atrial tachyarrhythmias before implantation. This study assessed the ability of device-based prevention and termination therapies to reduce the burden of spontaneous atrial tachyarrhythmias. Patients with a standard indication for the implantation of an ICD and 2 episodes of atrial tachyarrhythmias in the preceding year received a dual-chamber ICD (Medtronic 7250 Jewel AF) that uses pacing and shock therapies for prevention and/or termination of atrial tachyarrhythmias. In a multicenter trial, patients were randomized to 3-month periods with atrial therapies "on" or "off" and subsequently crossed over. Analysis was performed on the 52 of 269 patients who had episodes of atrial tachyarrhythmia and had >/=30 days of follow-up with atrial therapies on and off. The atrial therapies resulted in a reduction of atrial tachyarrhythmia burden from a mean of 58.5 to 7.8 h/mo. A paired analysis (Wilcoxon signed-rank test) showed that the median difference in burden (1.1 h/mo) was highly significant (P=0.007). When the subgroup of 41 patients treated only with atrial pacing therapies was analyzed, the reduction in burden persisted (P=0.01). In this study, patients with a standard ICD indication and atrial tachyarrhythmias had a significant reduction in atrial tachyarrhythmia burden with use of atrial pacing and shock therapies.

Splice-Switching Therapy for Spinal Muscular Atrophy

Directory of Open Access Journals (Sweden)

Katharina E. Meijboom

2017-06-01

Full Text Available Spinal muscular atrophy (SMA is a genetic disorder with severity ranging from premature death in infants to restricted motor function in adult life. Despite the genetic cause of this disease being known for over twenty years, only recently has a therapy been approved to treat the most severe form of this disease. Here we discuss the genetic basis of SMA and the subsequent studies that led to the utilization of splice switching oligonucleotides to enhance production of SMN protein, which is absent in patients, through a mechanism of exon inclusion into the mature mRNA. Whilst approval of oligonucleotide-based therapies for SMA should be celebrated, we also discuss some of the limitations of this approach and alternate genetic strategies that are currently underway in clinical trials.

Unorthodox alternative therapies marketed to treat Lyme disease.

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Lantos, Paul M; Shapiro, Eugene D; Auwaerter, Paul G; Baker, Phillip J; Halperin, John J; McSweegan, Edward; Wormser, Gary P

2015-06-15

Some patients with medically unexplained symptoms or alternative medical diagnoses suspect that they chronically suffer from the tick-borne infection Lyme disease. These patients are commonly targeted by providers of alternative therapies. This study was designed to identify and characterize the range of unorthodox alternative therapies advertised to patients with a diagnosis of Lyme disease. Internet searches using the Google search engine were performed to identify the websites of clinics and services that marketed nonantimicrobial therapies for Lyme disease. We subsequently used the PubMed search engine to identify any scientific studies evaluating such treatments for Lyme disease. Websites were included in our review so long as they advertised a commercial, nonantimicrobial product or service that specifically mentioned utility for Lyme disease. Websites with patient testimonials (such as discussion groups) were excluded unless the testimonial appeared as marketing on a commercial site. More than 30 alternative treatments were identified, which fell into several broad categories: these included oxygen and reactive oxygen therapy; energy and radiation-based therapies; nutritional therapy; chelation and heavy metal therapy; and biological and pharmacological therapies ranging from certain medications without recognized therapeutic effects on Borrelia burgdorgeri to stem cell transplantation. Review of the medical literature did not substantiate efficacy or, in most cases, any rationale for the advertised treatments. Providers of alternative therapies commonly target patients who believe they have Lyme disease. The efficacy of these unconventional treatments for Lyme disease is not supported by scientific evidence, and in many cases they are potentially harmful. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Comparison of semiquantitative fluorescence imaging and PET tracer uptake in mesothelioma models as a monitoring system for growth and therapeutic effects

Energy Technology Data Exchange (ETDEWEB)

Saito, Yuriko [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555 (Japan); Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675 (Japan); Furukawa, Takako [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Yoshida, Fukui, 910-1193 (Japan); Arano, Yasushi [Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675 (Japan); Fujibayashi, Yasuhisa [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555 (Japan); Biomedical Imaging Research Center, University of Fukui, Yoshida, Fukui, 910-1193 (Japan); Saga, Tsuneo [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555 (Japan)

2008-11-15

Introduction: Various techniques are available for in vivo imaging, and precise understanding of their characteristics is essential for effective use of the imaging results. We established human mesothelioma cell lines expressing red fluorescent protein (RFP) and examined their fluorescence intensity and uptake of positron emission tomography (PET) tracer analogs to compare their characteristics and assess their usefulness in the evaluation of therapeutics. Method: A human mesothelioma cell line was stably transfected to express RFP. Fluorescence, cell number and protein amount were measured during cell growth and treatment with cytotoxic reagents. In in vivo experiments, RFP-expressing cells were injected subcutaneously or into the pleural cavity of nude mice, and fluorescence images were taken with or without pemetrexed treatment. The uptake of [{sup 3}H]3'-deoxy-3'-fluorothymidine ([{sup 3}H]FLT) and [{sup 14}C]2-fluoro-2-deoxy-D-glucose ([{sup 14}C]FDG) under treatment with the above reagents in vitro and in vivo were examined. Results: Strong correlation was observed between fluorescence intensity and total cell number with or without cytotoxic treatment. The uptake of [{sup 3}H]FLT and [{sup 14}C]FDG decreased rapidly after the initiation of treatment with actinomycin D or cycloheximide. When treated with pemetrexed, the uptake of [{sup 3}H]FLT temporarily increased. The cells formed subcutaneous and orthotopic tumors, with fluorescence intensity correlating with tumor volume. The correlation was sustained under pemetrexed treatment. The uptake of [{sup 3}H]FLT in vivo increased significantly early after pemetrexed treatment. Conclusion: Fluorescence imaging could be used to semiquantitatively monitor tumor size, whereas PET could be used to monitor tumor response to therapeutic treatments, and especially, FLT might be a good marker of the response to anti-folate chemotherapeutics.

CT follow-up after radiation therapy for pituitary adenomas

International Nuclear Information System (INIS)

Rush, S.C.; Newall, J.

1988-01-01

Between 1973 and 1985, 105 patients received radiation therapy as all or part of their treatment for pituitary tumor at the New York University Medical Center. Of these, 48 patients underwent computed tomography (CT) at a minimum of 2 years following treatment, with detailed reports available for analysis of tumor regression. There were 28 men with a median age of 46 years (range, 18-71 years) and 20 women with a median age of 53 years (range, 28-80 years). Tumors were classified as secretory in 23 patients, nonsecretory in 21, and undetermined in four. Sixteen patients were treated with radiation therapy alone, 23 patients with surgery and radiation therapy, and the other with bromocriptine and radiation therapy, with or without surgery. With a median follow-up of 5 years (range, 2-14 years), 16 patients developed an empty sella, 25 patients had residual sellar mass, and seven patients had persistent extrasellar components or no change in their intrasellar mass. Among patients who did not have hypopituitarism at the inception of radiation therapy, five of 13 with empty sellas and 12 of 22 with residual mass subsequently required therapy. The authors conclude that residual mass is commonly found in long-term follow-up after radiation therapy, that isolated imaging studies revealing such findings after treatment in no way herald a diagnosis of recurrence, and that hypopituitarism following pituitary radiation therapy does not correlate with the ablation or persistence of tissue within the sella

Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery.

Science.gov (United States)

Kohler, Philipp; Kuster, Stefan P; Bloemberg, Guido; Schulthess, Bettina; Frank, Michelle; Tanner, Felix C; Rössle, Matthias; Böni, Christian; Falk, Volkmar; Wilhelm, Markus J; Sommerstein, Rami; Achermann, Yvonne; Ten Oever, Jaap; Debast, Sylvia B; Wolfhagen, Maurice J H M; Brandon Bravo Bruinsma, George J; Vos, Margreet C; Bogers, Ad; Serr, Annerose; Beyersdorf, Friedhelm; Sax, Hugo; Böttger, Erik C; Weber, Rainer; van Ingen, Jakko; Wagner, Dirk; Hasse, Barbara

2015-10-21

We identified 10 patients with disseminated Mycobacterium chimaera infections subsequent to open-heart surgery at three European Hospitals. Infections originated from the heater-cooler unit of the heart-lung machine. Here we describe clinical aspects and treatment course of this novel clinical entity. Interdisciplinary care and follow-up of all patients was documented by the study team. Patients' characteristics, clinical manifestations, microbiological findings, and therapeutic measures including surgical reinterventions were reviewed and treatment outcomes are described. The 10 patients comprise a 1-year-old child and nine adults with a median age of 61 years (range 36-76 years). The median duration from cardiac surgery to diagnosis was 21 (range 5-40) months. All patients had prosthetic material-associated infections with either prosthetic valve endocarditis, aortic graft infection, myocarditis, or infection of the prosthetic material following banding of the pulmonary artery. Extracardiac manifestations preceded cardiovascular disease in some cases. Despite targeted antimicrobial therapy, M. chimaera infection required cardiosurgical reinterventions in eight patients. Six out of 10 patients experienced breakthrough infections, of which four were fatal. Three patients are in a post-treatment monitoring period. Healthcare-associated infections due to M. chimaera occurred in patients subsequent to cardiac surgery with extracorporeal circulation and implantation of prosthetic material. Infections became clinically apparent after a time lag of months to years. Mycobacterium chimaera infections are easily missed by routine bacterial diagnostics and outcome is poor despite long-term antimycobacterial therapy, probably because biofilm formation hinders eradication of pathogens. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Cognitive-Behavioral Therapy for Depression Using Mind Over Mood: CBT Skill Use and Differential Symptom Alleviation.

Science.gov (United States)

Hawley, Lance L; Padesky, Christine A; Hollon, Steven D; Mancuso, Enza; Laposa, Judith M; Brozina, Karen; Segal, Zindel V

2017-01-01

Cognitive-behavioral therapy (CBT) for depression is highly effective. An essential element of this therapy involves acquiring and utilizing CBT skills; however, it is unclear whether the type of CBT skill used is associated with differential symptom alleviation. Outpatients (N = 356) diagnosed with a primary mood disorder received 14 two-hour group sessions of CBT for depression, using the Mind Over Mood protocol. In each session, patients completed the Beck Depression Inventory and throughout the week they reported on their use of CBT skills: behavioral activation (BA), cognitive restructuring (CR), and core belief (CB) strategies. Bivariate latent difference score (LDS) longitudinal analyses were used to examine patterns of differential skill use and subsequent symptom change, and multigroup LDS analyses were used to determine whether longitudinal associations differed as a function of initial depression severity. Higher levels of BA use were associated with a greater subsequent decrease in depressive symptoms for patients with mild to moderate initial depression symptoms relative to those with severe symptoms. Higher levels of CR use were associated with a greater subsequent decrease in depressive symptoms, whereas higher levels of CB use were followed by a subsequent increase in depressive symptoms, regardless of initial severity. Results indicated that the type of CBT skill used is associated with differential patterns of subsequent symptom change. BA use was associated with differential subsequent change as a function of initial severity (patients with less severe depression symptoms demonstrated greater symptom improvement), whereas CR use was associated with symptom alleviation and CB use with an increase in subsequent symptoms as related to initial severity. Copyright © 2016. Published by Elsevier Ltd.

[Conservative therapy of cartilage defects of the upper ankle joint].

Science.gov (United States)

Smolenski, U C; Best, N; Bocker, B

2008-03-01

Cartilage defects of the upper ankle joint reflect the problem that great force is transmitted and balanced out over a relatively small surface area. As a pathophysiological factor, cartilage-bone contusions play a significant role in the development of cartilage defects of the upper ankle joint. Physiotherapeutic procedures belong to the standard procedures of conservative therapy. The use and selection of the type of therapy is based on empirical considerations and experience and investigations on effectiveness of particular therapies are relatively rare. At present a symptom-oriented therapy of cartilage defects of the upper ankle joint seems to be the most sensible approach. It can be assumed that it makes sense that the symptomatic treatment of cartilage defects or initial stages of arthritis also includes the subsequent symptoms of pain, irritated condition and limited function. This leads to starting points for physiotherapy with respect to pain therapy, optimisation of pressure relationships, avoidance of pressure points, improvement of diffusion and pressure release. In addition to the differential physiotherapeutic findings, the determination of a curative, preventive or rehabilitative procedure is especially important. In physical therapy special importance is placed on a scheduled serial application corresponding to the findings, employing the necessary methods, such as physiotherapy, sport therapy, medical mechanics, manual therapy, massage, electrotherapy and warmth therapy. From this the findings-related therapy is proposed as a practical therapy concept: locomotive apparatus pain therapy, optimisation of pressure relationships, improvement of diffusion and decongestion therapy. Therapy options have been selected base on the current literature and are summarised in tabular form. The art of symptomatic therapy of cartilage defects of the upper ankle joint does not lie in the multitude of sometimes speculative procedures, but in the targeted selection

Reactions to abortion and subsequent mental health.

Science.gov (United States)

Fergusson, David M; Horwood, L John; Boden, Joseph M

2009-11-01

There has been continued interest in the extent to which women have positive and negative reactions to abortion. To document emotional reactions to abortion, and to examine the links between reactions to abortion and subsequent mental health outcomes. Data were gathered on the pregnancy and mental health history of a birth cohort of over 500 women studied to the age of 30. Abortion was associated with high rates of both positive and negative emotional reactions; however, nearly 90% of respondents believed that the abortion was the right decision. Analyses showed that the number of negative responses to the abortion was associated with increased levels of subsequent mental health disorders (Pabortion and reporting negative reactions had rates of mental health disorders that were approximately 1.4-1.8 times higher than those not having an abortion. Abortion was associated with both positive and negative emotional reactions. The extent of negative emotional reactions appeared to modify the links between abortion and subsequent mental health problems.

Morbidity and risk of subsequent diagnosis of HIV

DEFF Research Database (Denmark)

Søgaard, Ole S; Lohse, Nicolai; Østergaard, Lars Jørgen

2012-01-01

Early identification of persons with undiagnosed HIV infection is an important health care issue. We examined associations between diseases diagnosed in hospitals and risk of subsequent HIV diagnosis.......Early identification of persons with undiagnosed HIV infection is an important health care issue. We examined associations between diseases diagnosed in hospitals and risk of subsequent HIV diagnosis....

[Analysis of the clinical course of disease and subsequent dialysis therapy in a group of patients with rheumatoid arthritis and end-stage renal disease].

Science.gov (United States)

Majdan, Maria; Stepniak, Cezary; Piotrowicz, Sebastian; Broniek, Karina; Blajer, Beata; Bednarek-Skublewska, Anna

2005-04-01

The chronic nephropathy is often present in pts with rheumatoid arthritis (RA). In the study the authors retrospectively analyzed the clinical course of the disease and outcomes of subsequent dialysotherapy in a group of pts with RA and end-stage renal disease ESRD. During last 5 years ESRD connected with RA was found in 10 (8 F, 2 M) pts out of 325 chronically dialyzed pts (peritoneal dialysis and hemodialysis) representing 3,1% of pts. The mean age at the initiation of dialysotherapy in these pts was 62,8 +/- 10,2 (range 46-76) years. Mean time from the diagnosis of RA to the start of dialysotherapy was 18,8 +/- 11,6 (range 5-40) years. Earlier the patients were treated with many disease modifying antirheumatic drugs (DMARDS) also with glucocorticosteroids and many nonsteroidal anti-inflammatory drugs. It means that they had rather aggressive type of RA. Amyloidosis was histological confirmed in 6 pts (4 F, 2 M). Peritoneal dialysis (PD) was the first choice therapy in 8 pts (2 on APD, 6 on CAPD). The main complication was increased incidence of peritonitis. 3 pts died on PD after 5, 9, 24 months (respectively) of CAPD treatment. 3 pts were transferred to HD after 5, 15, 18 (respectively) months of CAPD because of recurrent peritonitis. 2 pts up to date continue PD (one 12 months, the second 46 months on CAPD). In 5 pts who needed hemodialysis treatment there have been very serious problems with permanent vascular access formation. All used permanent indwelling catheters (Permcath). We concluded that: occurrence of ESRD in pts with RA was connected with aggressive type of disease. Pts with RA represent a dialysis group that is particularly prone to complications of PD (enteric peritonitis) and HD (vascular access problems). It seems to be connected with secondary vasculitis often found in pts with aggressive type of RA.

Primary Occipital Ewing’s Sarcoma with Subsequent Spinal Seeding

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Ali Alqahtani

2017-01-01

Full Text Available Ewing’s sarcoma is a primary bone cancer that mainly affects the long bones. This malignancy is particularly common in pediatric patients. Primary cranial involvement accounts for 1% of cases, with occipital involvement considered extremely rare. In this case study, primary occipital Ewing’s sarcoma with a posterior fossa mass and subsequent relapse resulting in spinal seeding is reported. A 3-year-old patient presented with a 1-year history of left-sided headaches, localized over the occipital bone with progressive torticollis. Computed tomography (CT imaging showed a mass in the left posterior fossa compressing the brainstem. The patient then underwent surgical excision followed by adjuvant chemoradiation therapy. Two years later, the patient presented with severe lower back pain and urinary incontinence. Whole-spine magnetic resonance imaging (MRI showed cerebrospinal fluid (CSF seeding from the L5 to the S4 vertebrae. Primary cranial Ewing’s sarcoma is considered in the differential diagnosis of children with extra-axial posterior fossa mass associated with destructive permeative bone lesions. Although primary cranial Ewing’s sarcoma typically has good prognosis, our patient developed metastasis in the lower spine. Therefore, with CNS Ewing’s sarcoma, screening of the entire neural axis should be taken into consideration for early detection of CSF seeding metastasis in order to decrease the associated morbidity and mortality.

Cost and effectiveness studies in non-small cell lung cancer

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Pinar Yalcin-Balcik

2015-02-01

Full Text Available Lung cancer disease diagnosis and treatment is costly. As the numbers of inflicted rise so does the economic burden assumed for this cancer type. When the treatment expenditures are considered for all types of cancer, the lung cancer is thought to occupy a 20% share. The disease examined in two basic groups as small-cell lung cancer and non-small cell lung cancer (NSCLC is the most frequently encountered type of its kind nationally and in the World. This study considers the cost, effectiveness and cost effectiveness of platinum based chemotherapy medications with active ingredients pemetrexed and gemcitabine used for NSCLC. A review of studies relevant to the advanced stage NSCLC where majority of patients are positioned is foreseen to be useful to the decision makers since policy makers, regulating authorities and physicians require more information due to increased overall finance and costs, as well as treatment cost effectiveness. Furthermore, due to the entry attempt of pemetrexed active ingredient to the list of reimbursed medications for the first stage lung cancer treatment, it is assumed that a review of studies containing pemetrexed and gemcitabine will draw the attention of decision makers at the Social Security Instutition. [TAF Prev Med Bull 2015; 14(1.000: 55-64

Subsequent childbirth after a previous traumatic birth.

Science.gov (United States)

Beck, Cheryl Tatano; Watson, Sue

2010-01-01

Nine percent of new mothers in the United States who participated in the Listening to Mothers II Postpartum Survey screened positive for meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for posttraumatic stress disorder after childbirth. Women who have had a traumatic birth experience report fewer subsequent children and a longer length of time before their second baby. Childbirth-related posttraumatic stress disorder impacts couples' physical relationship, communication, conflict, emotions, and bonding with their children. The purpose of this study was to describe the meaning of women's experiences of a subsequent childbirth after a previous traumatic birth. Phenomenology was the research design used. An international sample of 35 women participated in this Internet study. Women were asked, "Please describe in as much detail as you can remember your subsequent pregnancy, labor, and delivery following your previous traumatic birth." Colaizzi's phenomenological data analysis approach was used to analyze the stories of the 35 women. Data analysis yielded four themes: (a) riding the turbulent wave of panic during pregnancy; (b) strategizing: attempts to reclaim their body and complete the journey to motherhood; (c) bringing reverence to the birthing process and empowering women; and (d) still elusive: the longed-for healing birth experience. Subsequent childbirth after a previous birth trauma has the potential to either heal or retraumatize women. During pregnancy, women need permission and encouragement to grieve their prior traumatic births to help remove the burden of their invisible pain.

Factors in Dry Period Associated with Intramammary Infection and Subsequent Clinical Mastitis in Early Postpartum Cows

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Kansuda Leelahapongsathon

2016-04-01

Full Text Available The objective of this study was to determine cow characteristics and farm management factors during the dry period associated with early postparturient intramammary infection (IMI and subsequent clinical mastitis (CM. Data were collected three times: before drying off (P1, during the dry period (P2, and 5 to 14 days after calving (P3, using questionnaires and farm investigation. Milk samples were aseptically collected for bacterial identification at P1 and P3. Factors associated with IMI and CM were analyzed using multiple logistic regression models. The final model showed that IMI in early postpartum was significantly associated with full insertion of dry cow antibiotic, dry cows in barns with a combination of tie and free stalls, body condition score (BCS in dry period and after calving, and milk yield before drying off. For IMI cows, factors significantly associated with clinical expression of mastitis were having daily barn cleaning, teat disinfected with alcohol before administration of dry cow therapy, BCS before drying off, milk yield before drying off, and days in milk at drying off. In conclusion, both cow and farm management factors are associated with the IMI rate and subsequent expression of clinical signs of mastitis in early postpartum cows.

Oral complications of cancer therapies. Mucosal alterations

International Nuclear Information System (INIS)

Squier, C.A.

1990-01-01

The initial effect of anticancer therapy, such as radiation and chemotherapy, is on the rapidly proliferating cells of the oral epithelium. As a consequence, the epithelium may show atrophy and ulceration. The sites of these alterations are related to the rate of epithelial proliferation. Regions of rapid proliferation, such as the oral lining mucosa, show a greater frequency of ulceration than masticatory mucosa or skin. Subsequent changes in the mucosa reflect damage to connective tissue, including fibroblasts and blood vessels. This results in hyalinization of collagen, hypovascularity, and ischemia. Indirect effects of anticancer therapy may include granulocytopenia and reduced salivary secretion, so that the protective mucin coating of the epithelium is compromised. These changes result in tissue with reduced barrier function and impaired ability to heal and to resist entry of pathogens, thus increasing the risk of systemic infections

Calcification of the bilateral basal ganglia after radiation therapy for childhood brain tumors

Energy Technology Data Exchange (ETDEWEB)

Kubo, Osami; Tajika, Yasuhiko; Sakairi, Mitsuhiko; Katahira, Masako; Shimizu, Takashi; Kitamura, Koichi

1987-12-01

Calcification of the basal ganglia subsequent to radiation therapy for childhood brain tumors has rarely been reported. Three cases of this calcification subsequent to radiation are presented here. Case 1 is a 7 year-old boy who underwent irradiation of 5000 rads locally for craniopharyngioma at the age of 4 years. Case 2 is a 4 year-old boy who was treated with irradiation of 4500 rads locally for cerebellar medulloblastoma at the age of 1 year. Case 3 is a 15 year-old girl who was treated with irradiation of 5000 rads to the brain and 3000 rads locally for suprasellar germinoma at the age of 11 years. In all these cases, the interval between radiation and evidence of calcification as detected only by CT scan, was more than 3 years and 2 cases are experiencing mild mental retardation. These findings suggest the possibility of long-term complications due to radiation therapy.

Enhanced cognitive behaviour therapy for adolescents with anorexia nervosa: An alternative to family therapy?

Science.gov (United States)

Dalle Grave, Riccardo; Calugi, Simona; Doll, Helen A.; Fairburn, Christopher G.

2013-01-01

A specific form of family therapy (family-based treatment) is the leading treatment for adolescents with anorexia nervosa. As this treatment has certain limitations, alternative approaches are needed. “Enhanced” cognitive behaviour therapy (CBT-E) is a potential candidate given its utility as a treatment for adults with eating disorder psychopathology. The aim of the present study was to establish, in a representative cohort of patients with marked anorexia nervosa, the immediate and longer term outcome following CBT-E. Forty-nine adolescent patients were recruited from consecutive referrals to a community-based eating disorder clinic. Each was offered 40 sessions of CBT-E over 40 weeks from a single therapist. Two-thirds completed the full treatment with no additional input. In these patients there was a substantial increase in weight together with a marked decrease in eating disorder psychopathology. Over the 60-week post-treatment follow-up period there was little change despite minimal subsequent treatment. These findings suggest that CBT-E may prove to be a cost-effective alternative to family-based treatment. PMID:23123081

Radiation therapy among atomic bomb survivors, Hiroshima and Nagasaki

International Nuclear Information System (INIS)

Pinkston, J.A.; Antoku, Shigetoshi; Russell, W.J.

1980-10-01

In the continuing evaluations of atomic bomb survivors for late radiation effects, not only doses from the A-bombs but those from other radiation sources must be considered, for the latter may be concomitantly acting factors causing bias among these investigations. In the present study, among 73 Hiroshima and 22 Nagasaki Adult Health Study (AHS) subjects who reported receiving radiation therapy, from 1970 through 1979, the medical records of 72 and 20, respectively, were reviewed, and 41 Hiroshima and 14 Nagasaki subjects were confirmed to have received radiation therapy. The data obtained in the present study were pooled with those of the previous investigation on radiation therapy exposures of AHS subjects prior to 1970. A total of 190 subjects have been documented as receiving radiation therapy and their doses were estimated. Energies used in treatments and diseases treated are discussed. Malignancies developed subsequent to radiation therapy in seven cases; five after treatment for malignancies and two after treatment for benign diseases. Neoplasms of 12 AHS subjects may have been induced by earlier radiation therapy; 5 in the earlier study and 7 in the present one. These investigations underscore the need for continued documentation of exposures to ionizing radiation for medical reasons, especially from sources incurring relatively high doses. Bias in assessments of late radiation effects among A-bomb survivors can thus be avoided. (author)

Eagle Syndrome: diagnostic imaging and therapy; Eagle Syndrom - Bildgebende Diagnostik und Therapie

Energy Technology Data Exchange (ETDEWEB)

Nickel, J.; Andresen, R. [Abt. fuer Bildgebende Diagnostik und Interventionelle Radiologie, Guestrower Krankenhaus, Akademisches Lehrkrankenhaus der Univ. Rostock (Germany); Sonnenburg, M. [Fachbelegarztpraxis fuer Mund, Kiefer, Gesichtschirurgie und Plastische Operationen, Guestrower Krankenhaus, Akademisches Lehrkrankenhaus der Univ. Rostock (Germany); Scheufler, O. [Klinik fuer Plastische, Wiederherstellungs- und Handchirurgie, Markus Krankenhaus, Akademisches Lehrkrankenhaus der Goethe Univ. Frankfurt am Main (Germany)

2004-07-01

In the case of clinical symptoms such as dysphagia, foreign-body sensation and chronic neck or facial pain close to the ear, an Eagle syndrome should be considered in the differential diagnosis. Rational diagnostics and therapy are elucidated on the basis of four case reports. Four patients presented in the out-patients clinic with chronic complaints on chewing and a foreign-body sensation in the tonsil region. Upon specific palpation below the mandibular angle, pain radiating into the ear region intensified. In all patients, local anaesthesia with lidocaine only led to a temporary remission of symptoms. Imaging diagnostics then performed initially included cranial survey radiograms according to Clementschitsch as well as in the lateral ray path and an OPTG. An axial spiral-CT was then performed using the thin-layer technique with subsequent 3-D reconstruction. Therapy consisted of elective resection with a lateral external incision from the retromandibular. From a symptomatic point of view, the cranial survey radiograms and the OPTG revealed hypertrophic styloid processes. The geometrically corrected addition of the axial CT images produced an absolute length of 51-58 mm. The 3-D reconstruction made it possible to visualise the exact spatial orientation of the styloid processes. An ossification of the stylohyoid ligament could definitely be ruled out on the basis of the imaging procedures. After resection of the megastyloid, the patients were completely free of symptoms. Spiral-CT with subsequent 3-D reconstruction is the method of choice for exact determination of the localisation and size of a megastyloid, while cranial survey radiograms according to Clementschitsch and in the lateral ray path or an OPTG can provide initial information. The therapy of choice is considered to be resection of the megastyloid, whereby an external lateral incision has proved effective. (orig.) [German] Bei klinischen Beschwerden wie Dysphagie, Fremdkoerpergefuehl und chronischen

The Relationship between Symptom Relief and Psychosocial Functional Improvement during Acute Electroconvulsive Therapy for Patients with Major Depressive Disorder.

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Lin, Ching-Hua; Yang, Wei-Cheng

2017-07-01

We aimed to compare the degree of symptom relief to psychosocial functional (abbreviated as "functional") improvement and explore the relationships between symptom relief and functional improvement during acute electroconvulsive therapy for patients with major depressive disorder. Major depressive disorder inpatients (n=130) requiring electroconvulsive therapy were recruited. Electroconvulsive therapy was generally performed for a maximum of 12 treatments. Symptom severity, using the 17-item Hamilton Depression Rating Scale, and psychosocial functioning (abbreviated as "functioning"), using the Modified Work and Social Adjustment Scale, were assessed before electroconvulsive therapy, after every 3 electroconvulsive therapy treatments, and after the final electroconvulsive therapy. Both 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale scores were converted to T-score units to compare the degrees of changes between depressive symptoms and functioning after electroconvulsive therapy. Structural equation modeling was used to test the relationships between 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale during acute electroconvulsive therapy. One hundred sixteen patients who completed at least the first 3 electroconvulsive therapy treatments entered the analysis. Reduction of 17-item Hamilton Depression Rating Scale T-scores was significantly greater than that of Modified Work and Social Adjustment Scale T-scores at assessments 2, 3, 4, and 5. The model analyzed by structural equation modeling satisfied all indices of goodness-of-fit (chi-square = 32.882, P =.107, TLI = 0.92, CFI = 0.984, RMSEA = 0.057). The 17-item Hamilton Depression Rating Scale change did not predict subsequent Modified Work and Social Adjustment Scale change. Functioning improved less than depressive symptoms during acute electroconvulsive therapy. Symptom reduction did not predict subsequent functional improvement

Cytarabine and daunorubicin or idarubicin in induction therapy of Acute Myeloid Leukemia patients

International Nuclear Information System (INIS)

Eivazi-Ziaei, J.; Kermani, I.A.; Nikanfar, A.; Maljaie, H.; Mahmoudpour, A.; Dolatkhah, R.

2010-01-01

Objectives: Acute myeloid leukemia (AML), the most common form of acute leukemia, is treated by remission induction and post-remission therapy. Remission induction is usually achieved by administration of cytarabine along with an anthracycline such as Daunorubicin (DAU) or Idarubicin (IDA). Our objective was see the benefits if any of IDA over DAU in AML therapy. Methodology: Eighty adult AML patients were enrolled in this study, where 40 received DAU and 40 were treated with IDA. Remission status in each subject was studied and response to therapy was subsequently analyzed using SPSS. Results: Complete remission, partial remission and no responsive status were 15, 19, and 14 respectively for patients on DAU and 14, 18, and 11 for patients on IDA protocol. No significant benefit was detected for IDA compared to DAU in response to therapy. Conclusion: We found no benefit in using IDA over DAU in induction therapy for AML patients treated in northwest of Iran. (author)

Recurrent miscarriage and antiphospholipid antibodies: prognosis of subsequent pregnancy.

NARCIS (Netherlands)

Cohn, D.M.; Goddijn, M.; Middeldorp, S.; Korevaar, J.C.; Dawood, F.; Farquharson, R.G.

2010-01-01

Background: Although women with antiphospholipid antibodies (APLAs) are at increased risk of recurrent miscarriage, the outcome of a subsequent pregnancy is not clearly elucidated. Objectives: To assess the pregnancy outcome of a subsequent pregnancy in women with APLAs and compare this outcome with

short history of anti-rheumatic therapy. IV. Corticosteroids

Directory of Open Access Journals (Sweden)

P. Marson

2011-06-01

Full Text Available In 1948 a corticosteroid compound was administered for the first time to a patient affected by rheumatoid arthritis by Philip Showalter Hench, a rheumatologist at the Mayo Clinic in Rochester, Minnesota (USA. He was investigating since 1929 the role of adrenal gland-derived substances in rheumatoid arthritis. For the discovery of cortisone and its applications in anti-rheumatic therapy, Hench, along with Edward Calvin Kendall and Tadeusz Reichstein, won the 1950 Nobel Prize for Medicine. In this review we summarize the main stages that led to the identification of the so-called compound E, which was used by Hench. We also consider the subsequent development of steroid therapy in rheumatic diseases, through the introduction of new molecules with less mineralocorticoid effects, such as prednisone, and more recently, deflazacort.

Exercise therapy after ultrasound-guided corticosteroid injections in patients with subacromial pain syndrome

DEFF Research Database (Denmark)

Ellegaard, Karen; Christensen, Robin; Rosager, Sara

2016-01-01

BACKGROUND: Subacromial pain syndrome (SAPS) accounts for around 50 % of all cases of shoulder pain. The most commonly used treatments are glucocorticosteroid (steroid) injections and exercise therapy; however, despite treatment SAPS patients often experience relapse of their symptoms. Therefore...... the clinical effect of combining steroid and exercise therapy is highly relevant to clarify. The aim of this randomized controlled trial was to investigate if exercise therapy added to steroid injection in patients with SAPS will improve the effect of the injection therapy on shoulder pain. METHODS......: In this two-arm randomized trial running over 26 weeks, patients with unilateral shoulder pain (> 4 weeks) and thickened subacromial bursa (> 2 mm on US) were included. At baseline all participants received two steroid injections into the painful shoulder with an interval of one week. Subsequently they were...

Hydroxyurea therapy contributes to infertility in adult men with sickle cell disease: a review.

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DeBaun, Michael R

2014-12-01

Hydroxyurea therapy, a chemotherapeutic agent, is the only US FDA approved therapy for the prevention of vaso-occlusive pain in sickle cell disease (SCD). The National Institutes of Health has sponsored two Phase III randomized, placebo-controlled trials, initially in adults, and subsequently in children with sickle cell anemia (SCA). Despite the overwhelming evidence that hydroxyurea therapy is beneficial to children and adults with SCA, individuals with SCA and their families express reservations about its use, in part because of the concerns about fertility, particularly in men. As adolescent boys with SCD are now expected to reach their reproductive years, a new concern is emerging about the role of hydroxyurea therapy as a barrier to their progeny. This review will systemically evaluate compromised fertility in men with SCD, and the evidence that hydroxyurea therapy is associated with further decreasing fertility in men with SCD.

Association of Periodontitis and Subsequent Depression

Science.gov (United States)

Hsu, Chih-Chao; Hsu, Yi-Chao; Chen, Hsuan-Ju; Lin, Che-Chen; Chang, Kuang-Hsi; Lee, Chang-Yin; Chong, Lee-Won; Kao, Chia-Hung

2015-01-01

Abstract Periodontitis is a systemic and chronic inflammatory disease associated with multiple physical conditions. Distress and depression are other problems affecting the progression of periodontitis. However, the causal relationship between depression and periodontitis has not been adequately investigated. This aim of this study was to determine the association between periodontitis and the subsequent development of depression. We identified 12,708 patients with newly diagnosed periodontitis from 2000 to 2005 and 50,832 frequency-matched individuals without periodontitis. Both groups were followed until diagnosed with depression, withdrawal from the National Health Insurance program, or the end of 2011. The association between periodontitis and depressio was analyzed using Cox proportional hazard regression models. The incidence density rate of depression was higher in the periodontitis group than in the nonperiodontitis group, with an adjusted hazard ratio of 1.73 (95% confidence interval 1.58–1.89) when adjusting for sex, age, and comorbidity. Cox models revealed that periodontitis was an independent risk factor for depression in patients, except for comorbidities of diabetes mellitus (DM), alcohol abuse, and cancer. Periodontitis may increase the risk of subsequent depression and was suggested an independent risk factor regardless of sex, age, and most comorbidities. However, DM, alcohol abuse, and cancer may prevent the development of subsequent depression because of DM treatment, the paradoxical effect of alcohol, and emotional distress to cancer, respectively. Prospective studies on the relationship between periodontitis and depression are warranted. PMID:26705230

Radiation therapy of peritoneal mesothelioma

International Nuclear Information System (INIS)

Lederman, G.; Recht, A.

1986-01-01

The role of radiation therapy in the treatment of peritoneal mesotheliomas remains ill-defined despite its association with the few long-term survivals reported for this disease. The rationale for local therapy is clear as the disease most often is confined to the peritoneal cavity at the time of initial diagnosis and remains there for much of the subsequent course. Effective local treatment of this intra-abdominal disease would likely improve survival. The absence of randomized studies has made analysis of the various treatments of the disease and the few reported success difficult. Nonetheless, scrutiny of the available data may offer insights and guide future clinical trials, as well as the clinician responsible for the treatment of current patients with peritoneal mesothelioma. The radiotherapeutic approach to oncology stresses anatomic considerations in an attempt to understand the patterns of spread of the primary tumor. The observed location and bulk of disease by clinical examination, radiologic study, surgical exploration, and autopsy suggest mechanisms of metastases (direct extension, lymphatic or hematogenous). This dictates the administration of radiation that best achieves a successful outcome

Epidemiological Patterns of Initial and Subsequent Injuries in Collegiate Football Athletes.

Science.gov (United States)

Williams, Jacob Z; Singichetti, Bhavna; Li, Hongmei; Xiang, Henry; Klingele, Kevin E; Yang, Jingzhen

2017-04-01

A body of epidemiological studies has examined football injuries and associated risk factors among collegiate athletes. However, few existing studies specifically analyzed injury risk in terms of initial or subsequent injuries. To determine athlete-exposures (AEs) and rates of initial and subsequent injury among collegiate football athletes. Descriptive epidemiological study. Injury and exposure data collected from collegiate football players from two Division I universities (2007-2011) were analyzed. Rate of initial injury was calculated as the number of initial injuries divided by the total number of AEs for initial injuries, while the rate for subsequent injury was calculated as the number of subsequent injuries divided by the total number of AEs for subsequent injury. Poisson regression was used to determine injury rate ratio (subsequent vs initial injury), with adjustment for other covariates. The total AEs during the study period were 67,564, resulting in an overall injury rate of 35.2 per 10,000 AEs. Rates for initial and subsequent injuries were 31.7 and 45.3 per 10,000 AEs, respectively, with a rate ratio (RR) of 1.4 for rate of subsequent injury vs rate of initial injury (95% CI, 1.1-1.9). Rate of injury appeared to increase with each successive injury. RR during games was 1.8 (95% CI, 1.1-3.0). The rate of subsequent injuries to the head, neck, and face was 10.9 per 10,000 AEs, nearly double the rate of initial injuries to the same sites (RR = 2.0; 95% CI, 1.1-3.5). For wide receivers, the rate of subsequent injuries was 2.2 times the rate of initial injuries (95% CI, 1.3-3.8), and for defensive linemen, the rate of subsequent injuries was 2.1 times the rate of initial injuries (95% CI, 1.1-3.9). The method used in this study allows for a more accurate determination of injury risk among football players who have already been injured at least once. Further research is warranted to better identify which specific factors contribute to this increased risk

Once-Daily Radiation Therapy for Inflammatory Breast Cancer

International Nuclear Information System (INIS)

Brown, Lindsay; Harmsen, William; Blanchard, Miran; Goetz, Matthew; Jakub, James; Mutter, Robert; Petersen, Ivy; Rooney, Jessica; Stauder, Michael; Yan, Elizabeth; Laack, Nadia

2014-01-01

Purpose: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. Methods and Materials: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. Results: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). Conclusions: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC

Embolisation of intracranial meningiomas without subsequent surgery

International Nuclear Information System (INIS)

Bendszus, M.; Solymosi, L.; Martin-Schrader, I.; Schlake, H.P.

2003-01-01

In an open, prospective study, we embolised intracranial meningiomas in seven patients, without subsequent surgery. Follow-up over a mean of 20 months included serial neurological examination, MRI and MR spectroscopy. Clinically, embolisation had no adverse effects. Symptomatic patients showed clinical improvement. On MRI marked tumour shrinkage occurred after embolisation in six patients, and was most pronounced during the first 6 months. In a young boy the tumour was unchanged despite complete angiographic devascularisation. Embolisation without subsequent surgery may cause substantial tumour shrinkage and thus be used in selected in patients. However, thorough follow-up is mandatory to ascertain the effects of embolisation. (orig.)

Changes in job strain and subsequent weight gain

DEFF Research Database (Denmark)

Vesterlund, Gitte Kingo; Keller, Amélie Cléo; Heitmann, Berit Lilienthal

2018-01-01

in 1999 between those who were rarely v. sometimes v. often busy in 1993 (P=0·03), with the largest weight gain in individuals with sustained high busyness in both years. Loss of influence between 1993 and 1999 was associated with larger subsequent weight gain than sustained high influence (P=0......Objective: Obesity as well as job strain is increasing, and job strain might contribute to weight gain. The objective of the current study was to examine associations between longitudinal alterations in the components of job strain and subsequent weight gain. Design: The study was designed...... as a prospective cohort study with three questionnaire surveys enabling measurement of job-strain alterations over 6 years and subsequent measurements of weight gain after further 10 years of follow-up. ANCOVA and trend analyses were conducted. Job demands were measured as job busyness and speed, and control...

Clinical Outcomes from Androgen Signaling-directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302.

Science.gov (United States)

Smith, Matthew R; Saad, Fred; Rathkopf, Dana E; Mulders, Peter F A; de Bono, Johann S; Small, Eric J; Shore, Neal D; Fizazi, Karim; Kheoh, Thian; Li, Jinhui; De Porre, Peter; Todd, Mary B; Yu, Margaret K; Ryan, Charles J

2017-07-01

In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302. Prostate-specific antigen (PSA) response was assessed. Median time to PSA progression was estimated using the Kaplan-Meier method. The PSA response rate (≥50% PSA decline, unconfirmed) was 44% and 67%, respectively. The median time to PSA progression was 3.9 mo (range 2.6-not estimable) for subsequent abiraterone acetate plus prednisone and 2.8 mo (range 1.8-not estimable) for subsequent enzalutamide. The majority of patients (68%) received intervening chemotherapy before subsequent abiraterone acetate plus prednisone or enzalutamide. While acknowledging the limitations of post hoc analyses and high censoring (>75%) in both treatment groups, these results suggest that subsequent therapy with abiraterone acetate plus prednisone or enzalutamide for patients who progressed on abiraterone acetate is associated with limited clinical benefit. This analysis showed limited clinical benefit for subsequent abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castration-resistant prostate cancer following initial treatment with abiraterone acetate plus prednisone. This analysis does not support prioritization of subsequent abiraterone acetate plus prednisone or enzalutamide following initial therapy with abiraterone acetate plus prednisone. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Short-term versus continuous antimicrobial therapy for asymptomatic bacteriuria in pregnancy.

Science.gov (United States)

Whalley, P J; Cunningham, F G

1977-03-01

Asymptomatic bacteriuria was identified in 300 pregnant women prior to the 28th week of gestation. In one group of 200 women short-term treatment with either nitrofurantoin or sulfamethizole was given for 14 days, and in another group of 100 women continuous therapy with one of these drugs was given for the remainder of gestation. Weekly urine cultures were obtained from all the women. Of the women treated with short-term therapy, 65% were abacteriuric for the remainder of pregnancy following one course of therapy, 24% became abacteriuric but subsequently relapsed, 2% had reinfection after becoming abacteriuric, and 9% demonstrated no response. Following treatment with a second course of short-term therapy, another 19% of these women were cured for the remainder of their pregnancy, and 3.5% responded to a third course. In the continuous therapy group, 88% of the women became abacteriuric for the remainder of the gestation, 3% demonstrated relapse, 2% developed reinfection, and 7% had no response to the first drug given. These data demonstrate that short-term administration of antimicrobials, when combined with surveillance for recurrent bacteriuria, is effective for the management of the pregnant woman with asymptomatic bacteriuria.

Modelling imperfect adherence to HIV induction therapy

Directory of Open Access Journals (Sweden)

Smith? Robert J

2010-01-01

Full Text Available Abstract Background Induction-maintenance therapy is a treatment regime where patients are prescribed an intense course of treatment for a short period of time (the induction phase, followed by a simplified long-term regimen (maintenance. Since induction therapy has a significantly higher chance of pill fatigue than maintenance therapy, patients might take drug holidays during this period. Without guidance, patients who choose to stop therapy will each be making individual decisions, with no scientific basis. Methods We use mathematical modelling to investigate the effect of imperfect adherence during the inductive phase. We address the following research questions: 1. Can we theoretically determine the maximal length of a possible drug holiday and the minimal number of doses that must subsequently be taken while still avoiding resistance? 2. How many drug holidays can be taken during the induction phase? Results For a 180 day therapeutic program, a patient can take several drug holidays, but then has to follow each drug holiday with a strict, but fairly straightforward, drug-taking regimen. Since the results are dependent upon the drug regimen, we calculated the length and number of drug holidays for all fifteen protease-sparing triple-drug cocktails that have been approved by the US Food and Drug Administration. Conclusions Induction therapy with partial adherence is tolerable, but the outcome depends on the drug cocktail. Our theoretical predictions are in line with recent results from pilot studies of short-cycle treatment interruption strategies and may be useful in guiding the design of future clinical trials.

START: an advanced radiation therapy information system.

Science.gov (United States)

Cocco, A; Valentini, V; Balducci, M; Mantello, G

1996-01-01

START is an advanced radiation therapy information system (RTIS) which connects direct information technology present in the devices with indirect information technology for clinical, administrative, information management integrated with the hospital information system (HIS). The following objectives are pursued: to support decision making in treatment planning and functional and information integration with the rest of the hospital; to enhance organizational efficiency of a Radiation Therapy Department; to facilitate the statistical evaluation of clinical data and managerial performance assessment; to ensure the safety and confidentiality of used data. For its development a working method based on the involvement of all operators of the Radiation Therapy Department, was applied. Its introduction in the work activity was gradual, trying to reuse and integrate the existing information applications. The START information flow identifies four major phases: admission, visit of admission, planning, therapy. The system main functionalities available to the radiotherapist are: clinical history/medical report linking function; folder function; planning function; tracking function; electronic mail and banner function; statistical function; management function. Functions available to the radiotherapy technician are: the room daily list function; management function: to the nurse the following functions are available: patient directing function; management function. START is a departmental client (pc-windows)-server (unix) developed on an integrated database of all information of interest (clinical, organizational and administrative) coherent with the standard and with a modular architecture which can evolve with additional functionalities in subsequent times. For a more thorough evaluation of its impact on the daily activity of a radiation therapy facility, a prolonged clinical validation is in progress.

Cognitive Behavioral Therapy and the Treatment of Posttraumatic Stress Disorder: Where Counseling and Neuroscience Meet

Science.gov (United States)

Makinson, Ryan A.; Young, J. Scott

2012-01-01

There is increasing evidence to support the biological basis of mental disorders. Subsequently, understanding the neurobiological context from which mental distress arises can help counselors appropriately apply cognitive behavioral therapy and other well-researched cognitive interventions. The purpose of this article is to describe the…

Physical therapy as an adjunctive treatment for severe osteoarthritis in a Komodo dragon (Varanus komodoensis).

Science.gov (United States)

Wolfe, Tammy Culpepper; Stringer, Elizabeth; Krauss, Sue; Trout, Tim

2015-03-01

This case report describes a new physical therapy technique, specifically the Wolfe Kinetic Technique, as adjunctive therapy in the treatment of severe osteoarthritis in a 20-yr-old Komodo dragon (Varanus komodoensis). This animal was managed with oral analgesics for 3 yr with fair to minimal response over time. Due to worsening of lameness and mobility, physical therapy was initiated. Ten treatment sessions were administered at 1-wk intervals. Within 1 mo the Komodo dragon exhibited marked improvement in gait and function, increased responsiveness to his environment, and increased mobility which continued to improve over the subsequent sessions. Although outcomes could not be measured by standardized objective measures, this study provides a reference for treatment of future cases and a foundation for future research substantiating treatment practices in animal physical therapy.

29 CFR 1919.30 - Examinations subsequent to unit tests.

Science.gov (United States)

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Examinations subsequent to unit tests. 1919.30 Section 1919... Treatment; Competent Persons § 1919.30 Examinations subsequent to unit tests. (a) After satisfactory completion of the unit proof load tests required by §§ 1919.27 and 1919.28, the cargo gear and all component...

Sub-sequence Factorization-an Effective Approach for Projective Reconstruction under Occlusion

Institute of Scientific and Technical Information of China (English)

LU Le; HU Zhanyi

2001-01-01

Projective reconstruction is a key step for 3D metric reconstruction from a sequence of images captured by an uncalibrated camera. Due to its inherent robustness, the factorization method is widely used in literatures. However, the main shortcoming of the standard factorization method is that it requires the corresponding points to appear across ALL the images. When large changes of view angles occur in the image sequence, or the scene is easy to be self-occluded, nearly it will be very difficult to have some corresponding points visible across all the images. But it is much easier for only several images to have enough correspondences required by factorization method. These images are called as a subsequence in the whole image set. In this paper,a sub-sequence factorization method is proposed to cope with the problem. The basic principle of the sub-sequence factorization method is to divide a long image sequence into several short subsequences according to its spatial continuity, and the standard factorization method is employed for each subsequence.Then, a novel alignment process is invoked to transform different reconstructions under different subsequences into one reference coordinates system. It is more practical as it only demands that there are enough correspondences in each subsequence, not the whole sequence. The proposed sub-sequence factorization method preserves the robustness aspect embedded in the standard factorization method. The experiments on synthetic and real images validate our proposed new method.

Faster Algorithms for Computing Longest Common Increasing Subsequences

DEFF Research Database (Denmark)

Kutz, Martin; Brodal, Gerth Stølting; Kaligosi, Kanela

2011-01-01

of the alphabet, and Sort is the time to sort each input sequence. For k⩾3 length-n sequences we present an algorithm which improves the previous best bound by more than a factor k for many inputs. In both cases, our algorithms are conceptually quite simple but rely on existing sophisticated data structures......We present algorithms for finding a longest common increasing subsequence of two or more input sequences. For two sequences of lengths n and m, where m⩾n, we present an algorithm with an output-dependent expected running time of and O(m) space, where ℓ is the length of an LCIS, σ is the size....... Finally, we introduce the problem of longest common weakly-increasing (or non-decreasing) subsequences (LCWIS), for which we present an -time algorithm for the 3-letter alphabet case. For the extensively studied longest common subsequence problem, comparable speedups have not been achieved for small...

Occupational Therapy's Role in Cancer Survivorship as a Chronic Condition.

Science.gov (United States)

Baxter, Mary Frances; Newman, Robin; Longpré, Sheila M; Polo, Katie M

Improved medical care has resulted in a documented increase in cancer survivors in the United States. Cancer survivors face challenges in participation across all facets of life as a result of the cancer and subsequent cancer treatments. Long-term and late-term sequelae can result in impairments in neurological systems, decreased stamina, loss of range of motion, and changes in sensation and cognition. These impairments are often long lasting, which categorizes cancer survivorship as a chronic condition. This categorization presents treatment challenges, especially in creating rehabilitation and habilitation service options that support cancer survivors. Occupational therapy provides a unique focus that can benefit cancer survivors as they face limitations in participation in all aspects of daily living. Research, advocacy, and education efforts are needed to focus on the specific rehabilitation and habilitation needs of cancer survivors to increase access to occupational therapy's distinct value. Copyright © 2017 by the American Occupational Therapy Association, Inc.

29 CFR 2700.23 - Review of a subsequent citation or order.

Science.gov (United States)

2010-07-01

... 29 Labor 9 2010-07-01 2010-07-01 false Review of a subsequent citation or order. 2700.23 Section... COMMISSION PROCEDURAL RULES Contests of Citations and Orders § 2700.23 Review of a subsequent citation or order. (a) The contesting party shall file any subsequent citation or order that modifies or terminates...

Advancements in anti-inflammatory therapy for dry eye syndrome.

Science.gov (United States)

McCabe, Erin; Narayanan, Srihari

2009-10-01

The goal of this literature review is to discuss recent discoveries in the pathophysiology of dry eye and the subsequent evolution of diagnostic and management techniques. The mechanisms of various anti-inflammatory treatments are reviewed, and the efficacy of common pharmacologic agents is assessed. Anti-inflammatory therapy is evaluated in terms of its primary indications, target population, and utility within a clinical setting. The Medline PubMed database and the World Wide Web were searched for current information regarding dry eye prevalence, pathogenesis, diagnosis, and management. After an analysis of the literature, major concepts were integrated to generate an updated portrayal of the status of dry eye syndrome. Inflammation appears to play a key role in perpetuating and sustaining dry eye. Discoveries of inflammatory markers found within the corneal and conjunctival epithelium of dry eye patients have triggered recent advancements in therapy. Pharmacologic anti-inflammatory therapy for dry eye includes 2 major categories: corticosteroids and immunomodulatory agents. Fatty acid and androgen supplementation and oral antibiotics have also shown promise in dry eye therapy because of their anti-inflammatory effects. Anti-inflammatory pharmacologic agents have shown great success in patients with moderate to severe dry eye when compared with alternative treatment modalities. A deeper understanding of the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday optometric practice.

Associations between mental disorders and subsequent onset of hypertension

Science.gov (United States)

Stein, Dan J.; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Bruffaerts, Ronny; de Jonge, Peter; Liu, Zharoui; Caldas-de-Almeida, Jose Miguel; O’Neill, Siobhan; Viana, Maria Carmen; Al-Hamzawi, Ali Obaid; Angermeyer, Mattias C.; Benjet, Corina; de Graaf, Ron; Ferry, Finola; Kovess-Masfety, Viviane; Levinson, Daphna; de Girolamo, Giovanni; Florescu, Silvia; Hu, Chiyi; Kawakami, Norito; Haro, Josep Maria; Piazza, Marina; Wojtyniak, Bogdan J; Xavier, Miguel; Lim, Carmen C.W.; Kessler, Ronald C.; Scott, Kate

2013-01-01

Background Previous work has suggested significant associations between various psychological symptoms (e.g. depression, anxiety, anger, alcohol abuse) and hypertension. However, the presence and extent of associations between common mental disorders and subsequent adult onset of hypertension remains unclear. Further, there is little data available on how such associations vary by gender or over life course. Methods Data from the World Mental Health Surveys (comprising 19 countries, and 52,095 adults) were used. Survival analyses estimated associations between first onset of common mental disorders and subsequent onset of hypertension, with and without psychiatric comorbidity adjustment. Variations in the strength of associations by gender and by life course stage of onset of both the mental disorder and hypertension were investigated. Results After psychiatric comorbidity adjustment, depression, panic disorder, social phobia, specific phobia, binge eating disorder, bulimia nervosa, alcohol abuse, and drug abuse were significantly associated with subsequent diagnosis of hypertension (with ORs ranging from 1.1 to 1.6). Number of lifetime mental disorders was associated with subsequent hypertension in a dose-response fashion. For social phobia and alcohol abuse, associations with hypertension were stronger for males than females. For panic disorder, the association with hypertension was particularly apparent in earlier onset hypertension. Conclusions Depression, anxiety, impulsive eating disorders, and substance use disorders disorders were significantly associated with the subsequent diagnosis of hypertension. These data underscore the importance of early detection of mental disorders, and of physical health monitoring in people with these conditions.. PMID:24342112

Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

Science.gov (United States)

Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

2015-01-01

In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

Antitumor effect of novel anti-podoplanin antibody NZ-12 against malignant pleural mesothelioma in an orthotopic xenograft model.

Science.gov (United States)

Abe, Shinji; Kaneko, Mika Kato; Tsuchihashi, Yuki; Izumi, Toshihiro; Ogasawara, Satoshi; Okada, Naoto; Sato, Chiemi; Tobiume, Makoto; Otsuka, Kenji; Miyamoto, Licht; Tsuchiya, Koichiro; Kawazoe, Kazuyoshi; Kato, Yukinari; Nishioka, Yasuhiko

2016-09-01

Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti-human podoplanin mAb, NZ-1, and a rat-human chimeric anti-human podoplanin antibody, NZ-8, derived from NZ-1, which induced antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against podoplanin-positive MPM cell lines. In this study, we showed the antitumor effect of NZ-1, NZ-8, and NZ-12, a novel rat-human chimeric anti-human podoplanin antibody derived from NZ-1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ-1 and rat NK (CD161a(+) ) cells inhibited the growth of tumors and the production of pleural effusion in NCI-H290/PDPN or NCI-H226 orthotopic xenograft mouse models. NZ-8 and human natural killer (NK) (CD56(+) ) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ-12 induced potent ADCC mediated by human MNC, compared with either NZ-1 or NZ-8. Antitumor effects were observed following treatment with NZ-12 and human NK (CD56(+) ) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ-12 mediated by human NK (CD56(+) ) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin-targeting immunotherapy using both NZ-12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Management benefits and safety of computed tomography in patients undergoing extracorporeal membrane oxygenation therapy: experience of a single centre

International Nuclear Information System (INIS)

Jepson, S.L.; Harvey, C.; Entwisle, J.J.; Peek, G.J.

2010-01-01

Aim: To evaluate the benefits and logistical safety of computed tomography (CT) imaging in patients undergoing extracorporeal membrane oxygenation (ECMO) therapy in a single institution. Materials and methods: Over a period of 25 months, 134 patients (80 neonates, 19 children, and 35 adults) underwent ECMO therapy at this institution. The imaging of these patients was reviewed to identify patients who had undergone CT imaging whilst on ECMO. Patient notes were retrospectively reviewed. CT findings and subsequent decisions were analysed to assess the benefit of CT imaging. Complications arising due to the logistics of performing the scan were analysed to assess the safety of performing CT in ECMO patients. Results: Of 134 patients, 14 (10%) had a total of 15 CT examinations whilst undergoing ECMO therapy. Indications for CT included new neurology, increased respiratory demand, and increasing requirement for high ECMO flows. There were no major complications and two minor complications associated with the logistics of performing a CT examination on an ECMO patient. Significant findings resulted from 73.3% (11/15) of the CT examinations, and in all 15 examinations information was provided that was used in making further management decisions, including, in some cases, withdrawal of ECMO therapy. Conclusion: With an experienced team, CT imaging of patients on ECMO can be performed safely. CT provides valuable information for subsequent management of patients undergoing ECMO therapy.

Treatment-associated subsequent neoplasms among long-term survivors of childhood cancer: the experience of the Childhood Cancer Survivor Study

Energy Technology Data Exchange (ETDEWEB)

Robison, Leslie L. [St. Jude Children' s Research Hospital, Department of Epidemiology and Cancer Control, Memphis, TN (United States)

2009-02-15

With improvements in survival among individuals diagnosed and treated for cancer there is an increasing recognition of the risk of long-term adverse effects of therapy. Second neoplasms represent one of the more serious late effects of treatment and are associated with a substantial level of morbidity and mortality. Survivors of childhood cancers, because of their potential longevity, are at particular risk for this adverse outcome. The Childhood Cancer Survivor Study is a large cohort consisting of adult survivors of childhood cancer diagnosed and treated between 1970 and 1986. The CCSS has provided important data to quantify radiation-associated risk for subsequent cancers including neoplasms of the breast, thyroid and central nervous system. (orig.)

Treatment-associated subsequent neoplasms among long-term survivors of childhood cancer: the experience of the Childhood Cancer Survivor Study

International Nuclear Information System (INIS)

Robison, Leslie L.

2009-01-01

With improvements in survival among individuals diagnosed and treated for cancer there is an increasing recognition of the risk of long-term adverse effects of therapy. Second neoplasms represent one of the more serious late effects of treatment and are associated with a substantial level of morbidity and mortality. Survivors of childhood cancers, because of their potential longevity, are at particular risk for this adverse outcome. The Childhood Cancer Survivor Study is a large cohort consisting of adult survivors of childhood cancer diagnosed and treated between 1970 and 1986. The CCSS has provided important data to quantify radiation-associated risk for subsequent cancers including neoplasms of the breast, thyroid and central nervous system. (orig.)

78 FR 40131 - Proposed Subsequent Arrangement

Science.gov (United States)

2013-07-03

... INFORMATION: This subsequent arrangement concerns the retransfer of 302,188 kg of U.S.-origin natural uranium..., Saskatchewan, Canada, to Springfields Fuels Ltd. in Lancashire, United Kingdom. The material, which is... arrangement concerning the retransfer of nuclear material of United States origin will not be inimical to the...

Complications Following the Insertion of Two Synthetic Mid-urethral Slings and Subsequent Removal.

Science.gov (United States)

Lee, Dominic; Bacsu, Chasta; Dillon, Benjamin; Zimmern, Philippe E

2017-06-28

To determine outcomes after removal of two synthetic mid-urethral slings (MUS) at a tertiary care center. Following IRB approval, a retrospective chart review of non-neurogenic, symptomatic women requiring re-operation after ≥2 MUS was performed. Data reviewed by a third party included: demographics, prior anti-incontinence surgery, complications, pelvic/urinary symptoms, subsequent investigations, surgical repair and outcomes (including UDI-6/IIQ-7 questionnaires) at a minimum 6 months follow-up. Cure was defined as being continent, no dyspareunia, and no additional surgical therapy. Between 2007 and 2014, 21 women met the inclusion criteria. Mean age was 57 years (range: 40-82) and mean follow-up was 30.2 months (range: 6-78). The majority of patients presented with one or more symptoms of voiding dysfunction (95%), urinary incontinence (86%), irritative voiding symptoms (62%), dyspareunia (57%), recurrent urinary tract infections (UTIs) (29%), vaginal extrusion (20%) and erosion involving the urinary tract (5%). Patients had a mean of 2 prior anti-incontinence procedures (range 2-3). Over two-thirds had a combination of retropubic and transobturator MUS. Mean number of pre-operative investigations was 3.5 (1-6) including voiding cystourethrogram, cystoscopy and urodynamics. Two patients had complete remission, 14 partial remission, and five failed. Mean postoperative total UDI-6 and IIQ-7 scores at last clinic visit were 10 (range: 0-16/SD 4.1) and 11 (range: 0-28/SD 10.3), respectively. The management of women with suboptimal outcomes following two synthetic MUS from transvaginal excision results in modest symptomatic improvement but low permanent complete remission and frequent need for additional therapies. © 2017 John Wiley & Sons Australia, Ltd.

The influence of children's pain memories on subsequent pain experience.

Science.gov (United States)

Noel, Melanie; Chambers, Christine T; McGrath, Patrick J; Klein, Raymond M; Stewart, Sherry H

2012-08-01

Healthy children are often required to repeatedly undergo painful medical procedures (eg, immunizations). Although memory is often implicated in children's reactions to future pain, there is a dearth of research directly examining the relationship between the 2. The current study investigated the influence of children's memories for a novel pain stimulus on their subsequent pain experience. One hundred ten healthy children (60 boys) between the ages of 8 and 12 years completed a laboratory pain task and provided pain ratings. Two weeks later, children provided pain ratings based on their memories as well as their expectancies about future pain. One month following the initial laboratory visit, children again completed the pain task and provided pain ratings. Results showed that children's memory of pain intensity was a better predictor of subsequent pain reporting than their actual initial reporting of pain intensity, and mediated the relationship between initial and subsequent pain reporting. Children who had negatively estimated pain memories developed expectations of greater pain prior to a subsequent pain experience and showed greater increases in pain ratings over time than children who had accurate or positively estimated pain memories. These findings highlight the influence of pain memories on healthy children's expectations of future pain and subsequent pain experiences and extend predictive models of subsequent pain reporting. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

An IP Framework for the Crew Pairing Problem Using Subsequence Generation

DEFF Research Database (Denmark)

Rasmussen, Matias Sevel; Lusby, Richard Martin; Ryan, David

In this paper we consider an important problem for the airline industry. The widely studied crew pairing problem is typically formulated as a set partitioning problem and solved using the branch-and-price methodology. Here we develop a new integer programming framework, based on the concept...... of subsequence generation, for solving the set partitioning formulation. In subsequence generation one restricts the number of permitted subsequent flights, that a crew member can turn to after completing any particular flight. By restricting the number of subsequences, the number of pairings in the problem...... decreases. The aim is then to dynamically add attractive subsequences to the problem, thereby increasing the number of possible pairings and improving the solution quality. Encouraging results are obtained on 19 real-life instances supplied by Air New Zealand and show that the described methodology...

Analysis of the value of post-radiation prostate biopsy in predicting subsequent disease progression

International Nuclear Information System (INIS)

Benda, R.; Shamsa, F.; Meetze, K.; Bolton, S.; Littrup, P.; Grignon, D.; Washington, T.; Forman, J.D.

1997-01-01

Purpose: To analyze the value of Transrectal ultrasound(TRUS), Color flow doppler(CFD) and Prostate specific antigen(PSA) in identifying residual disease in the prostate status post external beam radiation therapy and to determine the value of this pathologic information in predicting subsequent disease progression. Materials and Methods: As part of four prospective protocols, 146 patients had scheduled TRUS guided prostate biopsies 6-25 months status post radiation therapy. The stage distribution was: 13% T1, 51% T2, and 36% T3/T4. Fifty six percent had neo-adjuvant hormones. Conformal photon or mixed neutron/photon irradiation was given to a median 2 Gy/fraction equivalent dose of 77 Gy(range 74 to 84 Gy). Following treatment, patients were assessed by digital rectal exam (DRE), PSA and TRUS guided biopsies at 6, 12 and/or 18 months. The ultrasound and CFD results were scored as normal, suspicious or abnormal. Sextant biopsies were obtained as well as ultrasound guided biopsies from any abnormal ultrasound or doppler area. The biopsies, all read by one pathologist (DG), were graded as negative, marked, moderate, minimal therapeutic effect or positive. The median followup post radiation therapy was 33.6 months and post biopsy was 25.3 months. Comparisons were done by Kappa index with corresponding 95% CI, chi square and Fisher's exact tests. Results: Twenty-eight patients had biopsies at both six and 12-18 months. Overall 35% of patients had all negative cores, 30% had at least one core showing a marked therapeutic effect, and 35% had at least one core showing moderate or minimal therapeutic effect or were positive. Although CFD correlated with a positive biopsy in 9% and a suspicious doppler identified cancer in 15% of cases, an abnormal TRUS identified cancer in 29.5% biopsies ((49(166))). However, a serum PSA >1.5ng/ml at the time of biopsy predicted 61% of positive biopsies ((23(38))). A negative biopsy was associated with low stage (≤T2c, p=0.001), low pre

Aminopeptidase-resistant peptides are targeted to lysosomes and subsequently degraded

NARCIS (Netherlands)

Gillis, Judith M.; Benckhuijsen, Willemien; van Veen, Henk; Sanz, Alicia Sanz; Drijfhout, Jan W.; Reits, Eric A.

2011-01-01

Most cytoplasmic and nuclear proteins are degraded via the ubiquitin-proteasome system into peptides, which are subsequently hydrolyzed by downstream aminopeptidases. Inefficient degradation can lead to accumulation of protein fragments, and subsequent aggregation and toxicity. Whereas the role of

75 FR 346 - Proposed Subsequent Arrangement

Science.gov (United States)

2010-01-05

... Uses of Nuclear Energy. This subsequent arrangement concerns the retransfer of 28,409 kg of U.S.-origin... Fuels in Kanakawa-ken, Japan. The material, which is currently located at Cameco, Port Hope, Ontario, will be transferred to Global Nuclear Fuel, Kanakawa-ken, Japan to be fabricated into fuel pellets and...

Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

DEFF Research Database (Denmark)

Kongsted, Per; Svane, Inge M; Lindberg, Henriette

2016-01-01

To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

Impact of Selection Bias on Estimation of Subsequent Event Risk

NARCIS (Netherlands)

Hu, Yi Juan; Schmidt, Amand F.; Dudbridge, Frank; Holmes, Michael V; Brophy, James M.; Tragante, Vinicius; Li, Ziyi; Liao, Peizhou; Quyyumi, Arshed A.; McCubrey, Raymond O.; Horne, Benjamin D.; Hingorani, Aroon D; Asselbergs, Folkert W; Patel, Riyaz S.; Long, Qi; Åkerblom, Axel; Algra, Ale; Allayee, Hooman; Almgren, Peter; Anderson, Jeffrey L.; Andreassi, Maria G.; Anselmi, Chiara V.; Ardissino, Diego; Arsenault, Benoit J.; Ballantyne, Christie M.; Baranova, Ekaterina V.; Behloui, Hassan; Bergmeijer, Thomas O; Bezzina, Connie R; Bjornsson, Eythor; Body, Simon C.; Boeckx, Bram; Boersma, Eric H.; Boerwinkle, Eric; Bogaty, Peter; Braund, Peter S; Breitling, Lutz P.; Brenner, Hermann; Briguori, Carlo; Brugts, Jasper J.; Burkhardt, Ralph; Cameron, Vicky A.; Carlquist, John F.; Carpeggiani, Clara; Carruthers, Kathryn F.; Casu, Gavino; Condorelli, Gianluigi; Cresci, Sharon; Danchin, Nicolas; de Faire, Ulf; Deanfield, John; Delgado, Graciela; Deloukas, Panos; Direk, Kenan; Doughty, Robert N.; Drexel, Heinz; Duarte, Nubia E.; Dubé, Marie Pierre; Dufresne, Line; Engert, James C; Eriksson, Niclas; Fitzpatrick, Natalie; Foco, Luisa; Ford, Ian; Fox, Keith A; Gigante, Bruna; Gijsberts, Crystel M.; Girelli, Domenico; Gong, Yan; Gudbjartsson, Daniel F.; Hagström, Emil; Hartiala, Jaana; Hazen, Stanley L.; Held, Claes; Helgadottir, Anna; Hemingway, Harry; Heydarpour, Mahyar; Hoefer, Imo E.; Hovingh, G. Kees; Hubacek, Jaroslav A; James, Stefan; Johnson, Julie A; Jukema, J Wouter; Kaczor, Marcin P.; Kaminski, Karol A.; Kettner, Jiri; Kiliszek, Marek; Kleber, Marcus; Klungel, Olaf H.; Kofink, Daniel; Kohonen, Mika; Kotti, Salma; Kuukasjärvi, Pekka; Lagerqvist, Bo; Lambrechts, Diether; Lang, Chim C; Laurikka, Jari O.; Leander, Karin; Lee, Vei Vei; Lehtimäki, Terho; Leiherer, Andreas; Lenzini, Petra A.; Levin, Daniel; Lindholm, Daniel; Lokki, Marja-Liisa; Lotufo, Paulo A; Lyytikäinen, Leo-Pekka; Mahmoodi, B. Khan; Maitland-Van Der Zee, Anke H.; Martinelli, Nicola; März, Winfried; Marziliano, Nicola; McPherson, Ruth; Melander, Olle; Mons, Ute; Muehlschlegel, Jochen D.; Muhlestein, Joseph B.; Nelson, Cristopher P.; Cheh, Chris Newton; Olivieri, Oliviero; Opolski, Grzegorz; Palmer, Colin Na; Pare, Guillaume; Pasterkamp, Gerard; Pepine, Carl J; Pepinski, Witold; Pereira, Alexandre C.; Pilbrow, Anna P.; Pilote, Louise; Pitha, Jan; Ploski, Rafal; Richards, A. Mark; Saely, Christoph H.; Samani, Nilesh J; Samman-Tahhan, Ayman; Sanak, Marek; Sandesara, Pratik B.; Sattar, Naveed; Scholz, Markus; Siegbahn, Agneta; Simon, Tabassome; Sinisalo, Juha; Smith, J. Gustav; Spertus, John A.; Stefansson, Kari; Stewart, Alexandre F R; Stott, David J.; Szczeklik, Wojciech; Szpakowicz, Anna; Tanck, Michael W.T.; Tang, Wilson H.; Tardif, Jean-Claude; Ten Berg, Jur M.; Teren, Andrej; Thanassoulis, George; Thiery, Joachim; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Timmis, Adam; Trompet, Stella; Van de Werf, Frans; van der Graaf, Yolanda; Van Der Haarst, Pim; van der Laan, Sander W; Vilmundarson, Ragnar O.; Virani, Salim S.; Visseren, Frank L J; Vlachopoulou, Efthymia; Wallentin, Lars; Waltenberger, Johannes; Wauters, Els; Wilde, Arthur A M

2017-01-01

Background - Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic

Influences of multisensory experience on subsequent unisensory processing

Directory of Open Access Journals (Sweden)

Ladan eShams

2011-10-01

Full Text Available Multisensory perception has been the focus of intense research in recent years. It is now well established that crossmodal interactions are ubiquitous in perceptual processing and endow the system with improved precision, accuracy, processing speed, etc. While these findings have shed much light on principles and mechanisms of perception, ultimately it is not very surprising that multiple sources of information provide benefits in performance compared to a single source of information.Here, we argue that the more surprising recent findings are those showing that multisensory experience also influences the subsequent unisensory processing. For example, exposure to auditory-visual stimuli, can change the way auditory or visual stimuli are processed subsequently even in isolation. We review three sets of findings that represent three different types of learning ranging from perceptual learning, to sensory recalibration, to associative learning. In all these cases exposure to multisensory stimuli profoundly influences the subsequent unisensory processing. This diversity of phenomena may suggest that continuous modification of unisensory representations by multisensory relationships may be a general learning strategy used by the brain.

Patients' perspectives on statin therapy for treatment of hypercholesterolaemia: a qualitative study.

Science.gov (United States)

Tolmie, Elizabeth P; Lindsay, Grace M; Kerr, Susan M; Brown, Malcom R; Ford, Ian; Gaw, Allan

2003-07-01

Health Care Practitioners' attempts to implement secondary prevention targets for coronary heart disease (CHD) may be restricted by low rates of persistence with statin therapy. There is a need to understand why some patients, despite having established CHD and elevated cholesterol, do not comply with their prescribed statin regimen. To explore patients' perspectives on compliance with statin therapy. Primary care, West of Scotland. The research approach was qualitative. Thirty-three patients prescribed statin therapy and identified as having different patterns of compliance (poor moderate and good) were interviewed. The in-depth interviews were conducted on a one to one basis. Patients prescribed statin therapy for less than three months were excluded. Data were analysed thematically with the assistance of QSR Nudist. From analysis of the narrative data, two broad categories, i.e. 'Patient-health care provider communication' and 'Health beliefs' were identified. These categories encompassed six main themes: 'Initiation of therapy'; 'Subsequent feedback'; 'Sources of misconceptions'; 'Unconditional acceptance'; 'Conditional acceptance'; 'Deferment and Rejection'. Acceptance of and compliance with statin therapy appeared to be associated with the provision, interpretation and feedback of information during patient-practitioner consultations, and patients' beliefs about personal health status, cholesterol, and recommended cholesterol-lowering strategies. Patients' beliefs and understanding about cholesterol, and the role of cholesterol modifying strategies should be determined prior to the initiation of therapy and at appropriate intervals thereafter.

78 FR 72072 - Proposed Subsequent Arrangement

Science.gov (United States)

2013-12-02

... g of U.S.-origin atomized low-enriched uranium-7wt. % molybdenum powder, containing 365.638 g in the..., which is located at and was prepared by KAERI, will be used for the irradiation test of full-size fuel... subsequent arrangement concerning the retransfer of nuclear material of United States origin will not be...

Responder Status Criterion for Stepped Care Trauma-Focused Cognitive Behavioral Therapy for Young Children

Science.gov (United States)

Salloum, Alison; Scheeringa, Michael S.; Cohen, Judith A.; Storch, Eric A.

2015-01-01

Background: In order to develop Stepped Care trauma-focused cognitive behavioral therapy (TF-CBT), a definition of early response/non-response is needed to guide decisions about the need for subsequent treatment. Objective: The purpose of this article is to (1) establish criterion for defining an early indicator of response/non-response to the…

Diffuse brain calcification after radiation therapy in infantile cerebral malignant glioma

International Nuclear Information System (INIS)

Hondo, Hiroaki; Tanaka, Ryuichi; Yamada, Nobuhisa; Takeda, Norio

1987-01-01

We reported a case of infantile cerebral malignant glioma, which showed extensive intracranial calcification following radiation therapy, and reviewed the literature. A 4-month-old female infant was admitted to our hospital because of vomiting, enlargement of the head and convulsive seizures. Computerized tomography (CT) scans demonstrated a heterogeneously contrast-enhanced mass in the right temporo-parieto-occipital region and marked obstructive hydrocephalus. Subsequent to ventriculo-peritoneal shunt, biopsy was performed. The surgical specimen revealed anaplastic glioma. She then underwent whole brain irradiation with 1800 rads before subtotal removal and 3000 rads postoperatively. Calcification was first identified in the right frontal region and left basal ganglia 2.5 months after radiation therapy. At the age of 14 months, CT scans demonstrated extensive intracranial calcification in the cerebral hemispheres, basal ganglias, thalami, pons and cerebellum. A biopsy specimen of the frontal lobe revealed calcospherites of various sizes within and beside the walls of small vessels, but no tumor cells were observed. Cranial radiation therapy is a standard modality for treatment of children with neoplasm in the central nervous system. Since, however this therapy possibly causes long-term complications on the developing brain, it is important to plan radiation therapy for the brain tumor carefully. (author)

HIFU as a Neoadjuvant Therapy in Cancer Treatment

Science.gov (United States)

Zhong, P.; Xing, F.; Huang, X.; Zhu, H.; Lo, H. W.; Zhong, X.; Pruitt, S.; Robertson, C.

2011-09-01

To broaden the application spectrum of HIFU in cancer therapy, we performed a pilot experiment to evaluate the potential of using HIFU as a neoadjuvant therapy prior to surgery. Mice bearing wild-type B16F10 melanoma inoculated subcutaneously were either untreated (control) or treated by HIFU, CPA-7 or HIFU+CPA-7 before surgical resection of the primary tumor two days after HIFU treatment. The animals were then followed for four weeks or up to the humane endpoint to determine local recurrence, distant metastasis, and survival rate. The results demonstrate that animals treated by HIFU+CPA-7 (which is a small molecule that suppresses STAT3 activity) had a significantly lower recurrence rate, and slower growth of the recurrent tumor, with concomitantly higher survival rate, followed by those treated with CPA-7 and HIFU, respectively. Immunological assays revealed that CPA-7 treatment could significantly lower STAT3, and subsequently, Treg activities. In particular, the combination of HIFU and CPA-7 can induce a much stronger anti-tumor immune response than HIFU or surgery alone, as assessed by CTL and IFN-γ secretion. Overall, our results suggest that HIFU in combination with immunotherapy strategies has the potential to be used as a neoadjuvant therapy to prime the host with a strong anti-tumor immune response before surgical resection of the primary tumor. This multimodality, combinational therapy has the potential to greatly broaden the range of HIFU applications in cancer therapy with lower tumor recurrence and improved survival rate.

Comparison of single-agent chemotherapy and targeted therapy to first-line treatment in patients aged 80 years and older with advanced non-small-cell lung cancer

Directory of Open Access Journals (Sweden)

Zhang QQ

2015-04-01

Full Text Available Qianqian Zhang,1 Zhehai Wang,2 Jun Guo,2 Liyan Liu,2 Xiao Han,2 Minmin Li,1 Shu Fang,1 Xiang Bi,1 Ning Tang,1 Yang Liu1 1School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, 2Department of Oncology, Shandong Cancer Hospital, Jinan, People’s Republic of China Purpose: The aim of this study was to compare single-agent chemotherapy with targeted therapy in initial treatment and to explore a better choice of treatment for patients aged 80 years and older with advanced non-small-cell lung cancer (NSCLC.Patients and methods: A retrospective chart review was conducted for 136 patients aged 80 years and older who were cytopathologically diagnosed and staged as advanced (stage IIIB or IV NSCLC. The patient population was divided into two treatment groups: 78 patients were allocated to the chemotherapy group (group A, pemetrexed or gemcitabine or docetaxel as a single agent, and 60 patients were allocated to another group and received epidermal growth factor-receptor tyrosine-kinase inhibitors (group B, erlotinib or gefitinib as a single agent. The primary end points were overall survival (OS and progression-free survival (PFS, and the secondary end points were response rate, disease-control rate, safety, and quality of life.Results: In group A and group B, respectively, the median PFS was 2 versus 4 months (P=0.013, and the median OS was 8 versus 16 months (P=0.025. The 1- and 2-year survival rates of the two groups were 23.7% (group A, 18 of 76 versus 76.7% (group B, 46 of 60 and 13.2% (group A, ten of 76 versus 10% (group B, six of 60, respectively. The response rate and disease-control rate were 28.9% versus 36.7% (P=0.39 and 57.9% versus 76.7% (P=0.022 in group A and group B, respectively.Conclusion: Elders aged 80 years and over with advanced NSCLC in group B had longer PFS and OS compared with group A. It was well tolerated in group B because of the mild adverse effects. Targeted therapy can be

Evaluation of a novel radiofolate in tumour-bearing mice: promising prospects for folate-based radionuclide therapy

Energy Technology Data Exchange (ETDEWEB)

Mueller, Cristina [Paul Scherrer Institute, Center for Radiopharmaceutical Science ETH-PSI-USZ, Villigen PSI (Switzerland); Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Mindt, Thomas L. [ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland); Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Science ETH-PSI-USZ, Villigen PSI (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

2009-06-15

Folate-based radiopharmaceuticals have the potential to be used for imaging and therapy of tumours positive for the folate receptor (FR). We describe the in vitro and in vivo evaluation of a DOTA-folate conjugate. Radiolabelling of the DOTA-folate was carried out via standard procedures using {sup 111}InCl{sub 3} and {sup 177}LuCl{sub 3}, respectively. The distribution coefficient (log D) was determined in octanol/PBS (pH 7.4). Tissue distribution was investigated in nude mice bearing KB tumour xenografts at different time points after administration of {sup 111}In-DOTA-folate (radiofolate 1) or {sup 177}Lu-DOTA-folate (radiofolate 2) (1 MBq, 1 nmol per mouse). Pemetrexed (PMX, 400 {mu}g) was injected 1 h prior to the radiofolate in order to reduce renal uptake. Images were acquired with a SPECT/CT camera 24 h after injection of the radiofolate (40-50 MBq, 3 nmol per mouse). The hydrophilic character of the DOTA-folate was represented by a low log D value (radiofolate 1 -4.21{+-}0.11). In vivo, maximal tumour uptake was found 4 h after injection (radiofolate 1 5.80{+-}0.55% ID/g; radiofolate 2 7.51{+-}1.25% ID/g). In FR-positive kidneys there was considerable accumulation of the radiofolates (radiofolate 1 55.88{+-}3.91% ID/g; radiofolate 2 57.22{+-}11.05% ID/g; 4 h after injection). However, renal uptake was reduced by preinjection of PMX (radiofolate 1 9.52{+-}1.07% ID/g; radiofolate 2 13.43{+-}0.54% ID/g; 4 h after injection) whereas the tumour uptake was retained (radiofolate 1 6.32{+-}0.41% ID/g; radiofolate 2 8.99{+-}0.43% ID/g; 4 h after injection). SPECT/CT images clearly confirmed favourable tissue distribution of the novel radiofolates and the positive effect of PMX. The preliminary requirements for the therapeutic use of the novel DOTA-folate are met by its favourable tissue distribution that can be ascribed to its hydrophilic properties and combined administration with PMX. (orig.)

[Relapse prevention program consisting of coping skills training, cue exposure treatment, and letter therapy for Japanese alcoholic men who relapsed after standard cognitive-behavioral therapy].

Science.gov (United States)

Yokoyama, Akira; Matsushita, Sachio; Toyama, Tomomi; Nakayama, Hideki; Takimura, Tsuyoshi; Kimura, Mitsuru; Yoneda, Junichi; Maesato, Hitoshi; Mizukami, Takeshi; Higuchi, Susumu; Yokoyama, Tetsuji

2015-04-01

Coping skills training (CST) and cue exposure treatment (CET) have yielded favorable outcomes when used to treat alcoholics. We conducted 6-week inpatient programs that consisted of 9 CST group sessions (n = 117) during 2005-2009 and 9 CST group sessions plus 4 CET group sessions (n = 49) during 2009-2011 and subsequent 1-year letter therapy for Japanese alcoholic men who had relapsed and been readmitted after standard cognitive-behavioral inpatient therapy. When patients received a letter containing encouraging words every 2 weeks, they were asked to reread their CST and CET records and to respond to the letter by marking drinking days on a calendar and naming the skills on a list of the 9 CST themes and CET that were useful for maintaining abstinence during that 2-week period. The estimated percentages of achievement of 30 or fewer drinking days during the one year of letter therapy were 36.1 - 45.8%. 'Non-smoking', '2nd admission', and 'After age-limit job retirement' were significant factors in achieving good outcomes. The 'usefulness' responses for 'Increasing pleasant activities', 'CET', 'Anger management', ' Managing negative thinking', 'Problem solving', and ' Seemingly irrelevant decisions' as percentages of overall responses to the letters were significantly higher, in order of decreasing percentages, in the achiever group than in the non-achiever group, but the differences between the groups in ' Managing urges to drink', ' Drink refusal skills', ' Planning for emergencies', and ' Receiving criticism about drinking' were not significant. The odds ratios for achievement of 30 or fewer drinking days during the 1-year period increased significantly by 1.15 -1.31 fold per 10% increment in the 'usefulness' ratio for 'Increasing pleasant activities'. The difference in percentage achievement between the group treated by CST alone and the group treated by CST plus CET was not significant. In conclusion, some coping skills were more useful for relapse prevention

Gene therapy and angiogenesis in patients with coronary artery disease

DEFF Research Database (Denmark)

Kastrup, Jens

2010-01-01

-blind placebo-controlled trials could not confirm the initial high efficacy of either the growth factor protein or the gene therapy approaches observed in earlier small trials. The clinical studies so far have all been without any gene-related serious adverse events. Future trials will focus on whether...... an improvement in clinical results can be obtained with a cocktail of growth factors or by a combination of gene and stem cell therapy in patients with severe coronary artery disease, which cannot be treated effectively with current treatment strategies....... of VEGF and FGF in patients with coronary artery disease. The initial small and unblinded studies with either recombinant growth factor proteins or genes encoding growth factors were encouraging, demonstrating both clinical improvement and evidence of angiogenesis. However, subsequent larger double...

24 CFR 904.115 - Achievement of ownership by subsequent homebuyers.

Science.gov (United States)

2010-04-01

... of the LHA's debt, if there are any subsequent homebuyers who have not acquired ownership of their... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Achievement of ownership by... Description § 904.115 Achievement of ownership by subsequent homebuyers. (a) Definition. In the event the...

Magnetic Hyperthermia and Radiation Therapy: Radiobiological Principles and Current Practice †

Directory of Open Access Journals (Sweden)

Spiridon V. Spirou

2018-06-01

Full Text Available Hyperthermia, though by itself generally non-curative for cancer, can significantly increase the efficacy of radiation therapy, as demonstrated by in vitro, in vivo, and clinical results. Its limited use in the clinic is mainly due to various practical implementation difficulties, the most important being how to adequately heat the tumor, especially deep-seated ones. In this work, we first review the effects of hyperthermia on tissue, the limitations of radiation therapy and the radiobiological rationale for combining the two treatment modalities. Subsequently, we review the theory and evidence for magnetic hyperthermia that is based on magnetic nanoparticles, its advantages compared with other methods of hyperthermia, and how it can be used to overcome the problems associated with traditional techniques of hyperthermia.

What Makes Offenders with an Intellectual Disability Ready to Engage with Psychological Therapy? A Qualitative Study

Science.gov (United States)

Breckon, Susan E.; Smith, Ian C.; Daiches, Anna

2013-01-01

Although there are established links between measures of readiness for psychological therapy in offenders and subsequent reduction in recidivism rates there has been a lack of theoretical research considering this process within the intellectual disability (ID) offender population. Grounded theory methodology was used to explore the process by…

Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy

Energy Technology Data Exchange (ETDEWEB)

Andrys, C.; Borska, L.; Pohl, D.; Fiala, Z.; Hamakova, K.; Krejsek, J. [Faculty Hospital, Hradec Kralove (Czech Republic). Dept. of Clinical Immunology & Allergy

2007-03-15

Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. It was found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

Role of PET in gene therapy

International Nuclear Information System (INIS)

Lee, Kyung Han

2002-01-01

In addition to the well-established use of positron emission tomography (PET) in clinical oncology, novel roles for PET are rapidly emerging in the field of gene therapy. Methods for controlled gene delivery to living bodies, made available through advances in molecular biology, are currently being employed in animals for reasearch purposes and in humans to treat diseases such as cancer. Although gene therapy is still in its early developmental stage, it is perceived that many serious illnesses could be treated successfully by the use of therapeutic gene delivery. A major challenge for the widespread use of human gene therapy is to achieve a controlled and effective delivery of foreign genes to target cells and subsequently, adequate levels of expression. As such, the availability of noninvasive imaging methods to accurately assess the location, duration, and level of transgene expression is critical for optimizing gene therapy strategies. Current endeavors to achieve this goal include methods that utilize magnetic resonance imaging, optical imaging, and nuclear imaging techniques. As for PET, reporter systems that utilize gene encoding enzymes that accumulate postion labeled substrates and those transcribing surface receptors that bind specific positron labeled ligands have been successfully developed. More recent advances in this area include improved reporter gene constructs and radiotracers, introduction of potential strategies to monitor endogenous gene expression, and human pilot studies evaluating the distribution and safety of reporter PET tracers. The remarkably rapid progress occuring in gene imaging technology indicates its importance and wide range of application. As such, gene imaging is likely to become a major and exciting new area for future application of PET technology

Role of PET in gene therapy

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Han [School of Medicine, Sungkyunkwan Univ., Seoul (Korea, Republic of)

2002-02-01

In addition to the well-established use of positron emission tomography (PET) in clinical oncology, novel roles for PET are rapidly emerging in the field of gene therapy. Methods for controlled gene delivery to living bodies, made available through advances in molecular biology, are currently being employed in animals for reasearch purposes and in humans to treat diseases such as cancer. Although gene therapy is still in its early developmental stage, it is perceived that many serious illnesses could be treated successfully by the use of therapeutic gene delivery. A major challenge for the widespread use of human gene therapy is to achieve a controlled and effective delivery of foreign genes to target cells and subsequently, adequate levels of expression. As such, the availability of noninvasive imaging methods to accurately assess the location, duration, and level of transgene expression is critical for optimizing gene therapy strategies. Current endeavors to achieve this goal include methods that utilize magnetic resonance imaging, optical imaging, and nuclear imaging techniques. As for PET, reporter systems that utilize gene encoding enzymes that accumulate postion labeled substrates and those transcribing surface receptors that bind specific positron labeled ligands have been successfully developed. More recent advances in this area include improved reporter gene constructs and radiotracers, introduction of potential strategies to monitor endogenous gene expression, and human pilot studies evaluating the distribution and safety of reporter PET tracers. The remarkably rapid progress occuring in gene imaging technology indicates its importance and wide range of application. As such, gene imaging is likely to become a major and exciting new area for future application of PET technology.

Quinolone and glycopeptide therapy for infection in mouse following exposure to mixed-field neutron-γ-photon radiation

International Nuclear Information System (INIS)

Brook, I.; Tom, S.P.; Ledney, G.D.

1993-01-01

The effects of increased doses of mixed-field neutron-γ-photon irradiation on bacterial translocation and subsequent sepsis, and the influence of antimicrobial therapy on these events, were studied in the C3H/HeN mouse. The results demonstrate a relationship between the doses of mixed-field radiation and the rates of infection due to Enterobacteriaceae. While L-ofloxacin therapy reduces the infection rate, prolongs survival and prevents mortality, the addition of a glycopeptide can enhance systemic infection by resistant bacteria in the irradiated host. (author)

Quinolone and glycopeptide therapy for infection in mouse following exposure to mixed-field neutron-[gamma]-photon radiation

Energy Technology Data Exchange (ETDEWEB)

Brook, I. (Naval Medical Research Inst., Bethesda, MD (United States) Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)); Tom, S.P.; Ledney, G.D. (Armed Forces Radiobiology Research Inst., Bethesda, MD (United States))

1993-12-01

The effects of increased doses of mixed-field neutron-[gamma]-photon irradiation on bacterial translocation and subsequent sepsis, and the influence of antimicrobial therapy on these events, were studied in the C3H/HeN mouse. The results demonstrate a relationship between the doses of mixed-field radiation and the rates of infection due to Enterobacteriaceae. While L-ofloxacin therapy reduces the infection rate, prolongs survival and prevents mortality, the addition of a glycopeptide can enhance systemic infection by resistant bacteria in the irradiated host. (author).

39 CFR 7.5 - Public notice of meetings, subsequent changes.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Public notice of meetings, subsequent changes. 7.5 Section 7.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE PUBLIC OBSERVATION (ARTICLE VII) § 7.5 Public notice of meetings, subsequent changes. (a) At least one...

Emergency surgery due to complications during molecular targeted therapy in advanced gastrointestinal stromal tumors (GIST)

International Nuclear Information System (INIS)

Rutkowski, P.; Nowecki, Z. I.; Dziewirski, W.; Ruka, W.; Siedlecki, J. A.; Grzesiakowska, U.

2010-01-01

Aim. The aim of the study was to assess the frequency and results of disease/treatment-related emergency operations during molecular targeted therapy of advanced gastrointestinal stromal tumors (GISTs). Methods. We analyzed emergency operations in patients with metastatic/inoperable GISTs treated with 1 st -line imatinib - IM (group I: 232 patients; median follow-up time 31 months) and 2 nd -line sunitinib - SU (group II: 43 patients; median follow-up 13 months; 35 patients in trial A6181036) enrolled into the Polish Clinical GIST Registry. Results. In group I 3 patients (1.3%) underwent emergency surgery due to disease/treatment related complications: one due to bleeding from a ruptured liver tumor (1 month after IM onset) and two due to bowel perforation on the tumor with subsequent intraperitoneal abscess (both 2 months after IM onset). IM was restarted 5-8 days after surgery and no complications in wound healing were observed. In group II 4 patients (9.5%) underwent emergency operations due to disease/treatment related complications: three due to bowel perforations on the tumor (2 days, 20 days and 10 months after SU onset; 1 subsequent death) and one due to intraperitoneal bleeding from ruptured, necrotic tumor (3.5 months after SU start). SU was restarted 12-18 days after surgery and no complications in wound healing were observed. Conclusions. Emergency operations associated with disease or therapy during imatinib treatment of advanced GISTs are rare. The frequency of emergency operations during sunitinib therapy is considered to be higher than during first line therapy with imatinib which may be associated with more advanced and more resistant disease or to the direct mechanism of sunitinib action, i.e. combining cytotoxic and antiangiogenic activity and thus leading to dramatic tumor response. Molecular targeted therapy in GISTs should always be conducted in cooperation with an experienced surgeon. (authors)

Risk Factors for Asthma Exacerbation and Treatment Failure in Adults and Adolescents with Well-Controlled Asthma during Continuation and Step Down Therapy.

Science.gov (United States)

DiMango, Emily; Rogers, Linda; Reibman, Joan; Gerald, Lynn B; Brown, Mark; Sugar, Elizabeth A; Henderson, Robert; Holbrook, Janet T

2018-06-04

Although national and international guidelines recommend reduction of asthma controller therapy or 'step-down" therapy in patients with well controlled asthma, it is expected that some individuals may experience worsening of asthma symptoms or asthma exacerbations during step-down. Characteristics associated with subsequent exacerbations during step-down therapy have not been well defined. The effect of environmental tobacco smoke (ETS) exposure on risk of treatment failure during asthma step down therapy has not been reported. To identify baseline characteristics associated with treatment failure and asthma exacerbation during maintenance and guideline-based step-down therapy. The present analysis uses data collected from a completed randomized controlled trial of optimal step-down therapy in patients with well controlled asthma taking moderate dose combination inhaled corticosteroids/long acting beta agonists. Participants were 12 years or older with physician diagnosed asthma and were enrolled between December 2011 and May 2014. An Emergency Room visit in the previous year was predictive of a subsequent treatment failure (HR 1.53 (1.06, 2.21 CI). For every 10% increase in baseline forced expiratory volume in one second percent predicted, the hazard for treatment failure was reduced by 14% (95% CI: 0.74-0.99). There was no difference in risk of treatment failure between adults and children, nor did duration of asthma increase risk of treatment failure. Age of asthma onset was not associated with increased risk of treatment failure. Unexpected emergency room visit in the previous year was the only risk factor significantly associated with subsequent asthma exacerbations requiring systemic corticosteroids. Time to treatment failure or exacerbation did not differ in participants with and without self-report of ETS exposure. The present findings can help clinicians identify patients more likely to develop treatment failures and exacerbations and who may therefore

How visual short-term memory maintenance modulates subsequent visual aftereffects.

Science.gov (United States)

Saad, Elyana; Silvanto, Juha

2013-05-01

Prolonged viewing of a visual stimulus can result in sensory adaptation, giving rise to perceptual phenomena such as the tilt aftereffect (TAE). However, it is not known if short-term memory maintenance induces such effects. We examined how visual short-term memory (VSTM) maintenance modulates the strength of the TAE induced by subsequent visual adaptation. We reasoned that if VSTM maintenance induces aftereffects on subsequent encoding of visual information, then it should either enhance or reduce the TAE induced by a subsequent visual adapter, depending on the congruency of the memory cue and the adapter. Our results were consistent with this hypothesis and thus indicate that the effects of VSTM maintenance can outlast the maintenance period.

Pretreatment CD4 cell slope and progression to AIDS or death in HIV-infected patients initiating antiretroviral therapy--the CASCADE collaboration: a collaboration of 23 cohort studies

NARCIS (Netherlands)

Wolbers, Marcel; Babiker, Abdel; Sabin, Caroline; Young, Jim; Dorrucci, Maria; Chêne, Geneviève; Mussini, Cristina; Porter, Kholoud; Bucher, Heiner C.; del Amo, Julia; Meyer, Laurence; Pillay, Deenan; Prins, Maria; Rosinska, Magda; Touloumi, Giota; Lodi, Sara; Coughlin, Kate; Walker, Sarah; Darbyshire, Janet; de Luca, Andrea; Fisher, Martin; Muga, Roberto; Kaldor, John; Kelleher, Tony; Ramacciotti, Tim; Gelgor, Linda; Cooper, David; Smith, Don; Gill, John; Jørgensen, Louise Bruun; Nielsen, Claus; Lutsar, Irja; Dabis, Francois; Thiebaut, Rodolphe; Masquelier, Bernard; Costagliola, Dominique; Guiguet, Marguerite; Vanhems, Philippe; Chaix, Marie-Laure; Ghosn, Jade; Boufassa, Faroudy; Hamouda, Osamah; Kucherer, Claudia; Pantazis, Nikos; Hatzakis, Angelos; Paraskevis, Dimitrios; Karafoulidoua, Anastasia; van der Helm, Jannie; Geskus, Ronald; Schuitemaker, Hanneke

2010-01-01

BACKGROUND: CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the

Diffuse stenotic change in large intracranial arteries following irradiation therapy for medulloblastoma

International Nuclear Information System (INIS)

Yamakami, Iwao; Sugaya, Yuichi; Sato, Masanori; Osato, Katunobu; Yamaura, Akira; Makino, Hiroyasu.

1990-01-01

We reported a case of a patient who developed a diffuse stenotic change in the large intracranial arteries and repeated episodes of cerebral infarction after irradiation therapy for medulloblastoma. A three-year-old girl underwent the subtotal removal of cerebellar medulloblastoma and the subsequent irradiation therapy in the whole brain and spine (30 Gy in the whole brain, 20 Gy in the local brain, and 25 Gy in the whole spine). Two years later, she again underwent surgery and irradiation therapy because a recurrence of medulloblastoma had manifested itself in the frontal lobe; (40 Gy in the whole brain, 20 Gy in the local brain, and 25 Gy in the whole spine). One and half years after the second irradiation, she started suffering from frequent and refractory cerebral ischemic attacks. Cerebral angiography revealed a diffuse narrowing, and multifocal stenoses in the bilateral anterior and middle cerebral arteries. Computerized tomography demonstrated multiple cerebral infarctions. Her neurological condition deteriorated because of recurring strokes and she died at ten years of age. Most of the reported cases of patients who developed stenotic arteriopathy were children in the first decade of their life, and who were irradiated for parasellar brain tumor of low malignancy. Stenotic arteriopathy after irradiation has rarely been recognized in patients with malignant brain tumor. However, life expectancy is increasing even for those with malignant brain tumor, and it may make stenotic arteriopathy after irradiation recognized more commonly in patients with malignant brain tumor. Careful irradiation and subsequent angiographical examination should be required even in patients with malignant brain tumor. (author)

A systematic review of randomized controlled trials using music therapy for children.

Science.gov (United States)

Mrázová, Marcela; Celec, Peter

2010-10-01

Music therapy is a promising approach widening the potential applications of psychotherapy. Music influences both, psychologic and physiologic parameters, and children are especially responsive to this form of therapy. Many aspects of its action mechanisms remain to be elucidated, underscoring the need for evidence-based medicine (EBM) for clinical use of music therapy. This review seeks to highlight some of the issues of music therapy research and to initiate a discussion about the need for international multicenter cooperation to bring scientifically sound evidence of the benefits of music therapy in pediatric patients. Scientific bibliographic databases were searched for randomized controlled trials on use of music therapy for children. Identified articles were evaluated according to criteria for scientific quality. Twenty-eight studies were identified. Most of the trials were biased by the number of participants, and some trials showed the need to improve design of control groups. Indeed, the novelty of this area of study has produced a large number of different studies (with variability in diagnoses, interventions, control groups, duration, and/or outcome parameters), and there is a need for a more homogeneous and systematic approach. Available studies highlight the need to address reproducibility issues. This analysis identifies the need for a subsequent series of clinical studies on the efficacy of music in the pediatric population, with more focus on eligibility criteria with respect to EBM and reproducibility.

Subsequent Shoulder Surgery After Isolated Arthroscopic SLAP Repair.

Science.gov (United States)

Mollon, Brent; Mahure, Siddharth A; Ensor, Kelsey L; Zuckerman, Joseph D; Kwon, Young W; Rokito, Andrew S

2016-10-01

To quantify the incidence of and identify the risk factors for subsequent shoulder procedures after isolated SLAP repair. New York's Statewide Planning and Research Cooperative System database was searched between 2003 and 2014 to identify individuals with the sole diagnosis of a SLAP lesion who underwent isolated arthroscopic SLAP repair. Patients were longitudinally followed up for a minimum of 3 years to analyze for subsequent ipsilateral shoulder procedures. Between 2003 and 2014, 2,524 patients met our inclusion criteria. After 3 to 11 years of follow-up, 10.1% of patients (254 of 2,524) underwent repeat surgical intervention on the same shoulder as the initial SLAP repair. The mean time to repeat shoulder surgery was 2.3 ± 2.1 years. Subsequent procedures included subacromial decompression (35%), debridement (26.7%). repeat SLAP repair (19.7%), and biceps tenodesis or tenotomy (13.0%). After isolated SLAP repair, patients aged 20 years or younger were more likely to undergo arthroscopic Bankart repair (odds ratio [OR], 2.91; 95% confidence interval [CI], 1.36-6.21; P = .005), whereas age older than 30 years was an independent risk factor for subsequent acromioplasty (OR, 2.3; 95% CI, 1.4-3.7; P surgery after isolated SLAP repair, often related to an additional diagnosis, suggesting that clinicians should consider other potential causes of shoulder pain when considering surgery for patients with SLAP lesions. In addition, the number of isolated SLAP repairs performed has decreased over time, and management of failed SLAP repair has shifted toward biceps tenodesis or tenotomy over revision SLAP repair in more recent years. Level III, case-control study. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Quinacrine enhances carmustine therapy of experimental rat glioma.

Science.gov (United States)

Reyes, S; Herrera, L A; Ostrosky, P; Sotelo, J

2001-10-01

The high rate of mutagenesis in malignant cells has been considered to be a primary factor in the appearance of chemotherapy-resistant cell clones in glioblastomas. Quinacrine binds strongly to deoxyribonucleic acid, preventing mutagenesis. We investigated whether quinacrine could improve carmustine therapy in C6 cell cultures and in C6 malignant gliomas implanted subcutaneously into Wistar rats. A potential chemopreventive effect of quinacrine on acquired resistance to carmustine therapy was studied in vitro and in vivo. Deoxyribonucleic acid damage was measured in cultured C6 cells by using the micronucleus test. Wistar rats with subcutaneously implanted C6 gliomas were treated with carmustine, quinacrine, or carmustine plus quinacrine, using pharmacological schemes similar to those used for human patients. The addition of quinacrine to cultured C6 cells did not modify carmustine-induced cytotoxicity; however, the deoxyribonucleic acid damage in surviving cells was minor, as indicated by the frequency of micronucleated cells. The surviving cells continued to be susceptible to a second exposure to carmustine, in contrast to non-quinacrine-treated control cells, which developed resistance to carmustine in a subsequent exposure (P < 0.05). The rate of tumor remission was higher for glioma-bearing rats treated with quinacrine plus carmustine, compared with rats treated with carmustine alone (P < 0.01). The addition of quinacrine to carmustine therapy increases the antineoplastic effect of the carmustine therapy. Our results suggest that chemical inhibition of mutagenesis in malignant glial cells during chemotherapy prevents the appearance of resistant clones.

Compression therapy in patients with venous leg ulcers.

Science.gov (United States)

Dissemond, Joachim; Assenheimer, Bernd; Bültemann, Anke; Gerber, Veronika; Gretener, Silvia; Kohler-von Siebenthal, Elisabeth; Koller, Sonja; Kröger, Knut; Kurz, Peter; Läuchli, Severin; Münter, Christian; Panfil, Eva-Maria; Probst, Sebastian; Protz, Kerstin; Riepe, Gunnar; Strohal, Robert; Traber, Jürg; Partsch, Hugo

2016-11-01

Wund-D.A.CH. is the umbrella organization of the various wound care societies in German-speaking countries. The present consensus paper on practical aspects pertinent to compression therapy in patients with venous leg ulcers was developed by experts from Germany, Austria, and Switzerland. In Europe, venous leg ulcers rank among the most common causes of chronic wounds. Apart from conservative and interventional wound and vein treatment, compression therapy represents the basis of all other therapeutic strategies. To that end, there are currently a wide variety of materials and systems available. While especially short-stretch bandages or multicomponent systems should be used in the initial decongestion phase, ulcer stocking systems are recommended for the subsequent maintenance phase. Another - to date, far less common - alternative are adaptive Velcro bandage systems. Medical compression stockings have proven particularly beneficial in the prevention of ulcer recurrence. The large number of treatment options currently available enables therapists to develop therapeutic concepts geared towards their patients' individual needs and abilities, thus resulting in good acceptance and adherence. Compression therapy plays a crucial role in the treatment of patients with venous leg ulcers. In recent years, a number of different treatment options have become available, their use and application differing among German-speaking countries. The present expert consensus is therefore meant to outline concrete recommendations for routine implementation of compression therapy in patients with venous leg ulcers. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

Parental views on withdrawing life-sustaining therapies in critically ill children.

Science.gov (United States)

Michelson, Kelly Nicole; Koogler, Tracy; Sullivan, Christine; Ortega, María del Pilar; Hall, Emily; Frader, Joel

2009-11-01

To broaden existing knowledge of pediatric end-of-life decision making by exploring factors described by parents of patients in the pediatric intensive care unit (PICU) as important/influential if they were to consider withdrawing life-sustaining therapies. Quantitative and qualitative analysis of semi-structured one-on-one interviews. The PICUs at 2 tertiary care hospitals. English- or Spanish-speaking parents who were older than 17 years and whose child was admitted to the PICU for more than 24 hours to up to 1 week. Semi-structured one-on-one interviews. Forty of 70 parents (57%) interviewed said they could imagine a situation in which they would consider withdrawing life-sustaining therapies. When asked if specific factors might influence their decision making, 64% of parents said they would consider withdrawing life-sustaining therapies if their child were suffering; 51% would make such a decision based on quality-of-life considerations; 43% acknowledged the influence of physician-estimated prognosis in their decision; and 7% said financial burden would affect their consideration. Qualitative analysis of their subsequent comments identified 9 factors influential to parents when considering withdrawing life-sustaining therapies: quality of life, suffering, ineffective treatments, faith, time, financial considerations, general rejection of withdrawing life-sustaining therapies, mistrust/doubt toward physicians, and reliance on self/intuition. Parents describe a broad range of views regarding possible consideration of withdrawing life-sustaining therapies for their children and what factors might influence such a decision.

CAR-T Cell Therapies From the Transfusion Medicine Perspective.

Science.gov (United States)

Fesnak, Andrew; Lin, ChieYu; Siegel, Don L; Maus, Marcela V

2016-07-01

The use of chimeric antigen receptor (CAR)-T cell therapy for the treatment of hematologic malignancies has generated significant excitement over the last several years. From a transfusion medicine perspective, the implementation of CAR-T therapy as a potential mainstay treatment for not only hematologic but also solid-organ malignancies represents a significant opportunity for growth and expansion. In this review, we will describe the rationale for the development of genetically redirected T cells as a cancer therapeutic, the different elements that are required to engineer these cells, as well as an overview of the process by which patient cells are harvested and processed to create and subsequently validate CAR-T cells. Finally, we will briefly describe some of the toxicities and clinical efficacy of CAR-T cells in the setting of patients with advanced malignancy. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypokalaemia and subsequent hyperkalaemia in hospitalized patients

NARCIS (Netherlands)

M.J. Crop (Meindert); E.J. Hoorn (Ewout); J. Lindemans (Jan); R. Zietse (Bob)

2007-01-01

textabstractBackground. The objective was to study the epidemiology of hypokalaemia [serum potassium concentration (SK) <3.5 mmol/l] in a general hospital population, specifically focusing on how often and why patients develop subsequent hyperkalaemia (SK<5.0 mmol/l). Methods. In a 3-month

Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

DEFF Research Database (Denmark)

Trickey, Adam; May, Margaret T; Vehreschild, Jorg-Janne

2016-01-01

OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing to the Antiretro......OBJECTIVES: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. METHODS: We used data from 18 European and North American HIV cohort studies contributing...... to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. RESULTS: During 50,593 person...... years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict...

Dose distribution following selective internal radiation therapy

International Nuclear Information System (INIS)

Fox, R.A.; Klemp, P.F.; Egan, G.; Mina, L.L.; Burton, M.A.; Gray, B.N.

1991-01-01

Selective Internal Radiation Therapy is the intrahepatic arterial injection of microspheres labelled with 90Y. The microspheres lodge in the precapillary circulation of tumor resulting in internal radiation therapy. The activity of the 90Y injected is managed by successive administrations of labelled microspheres and after each injection probing the liver with a calibrated beta probe to assess the dose to the superficial layers of normal tissue. Predicted doses of 75 Gy have been delivered without subsequent evidence of radiation damage to normal cells. This contrasts with the complications resulting from doses in excess of 30 Gy delivered from external beam radiotherapy. Detailed analysis of microsphere distribution in a cubic centimeter of normal liver and the calculation of dose to a 3-dimensional fine grid has shown that the radiation distribution created by the finite size and distribution of the microspheres results in an highly heterogeneous dose pattern. It has been shown that a third of normal liver will receive less than 33.7% of the dose predicted by assuming an homogeneous distribution of 90Y

The Treatment of Clozapine-Withdrawal Delirium with Electroconvulsive Therapy

Directory of Open Access Journals (Sweden)

Anish Modak

2017-01-01

Full Text Available Clozapine, a commonly used atypical antipsychotic, can precipitate a severe withdrawal syndrome. In this report, we describe a case of delirium with catatonic features emerging after the immediate cessation of clozapine subsequent to concerns of developing neuroleptic malignant syndrome. After multiple treatments were found to be inefficacious, electroconvulsive therapy (ECT was initiated, resulting in significant improvement. A literature search revealed six previous cases of clozapine-withdrawal syndromes of varied symptomatology treated with ECT. To our knowledge, the present case represents the first reported clozapine-withdrawal delirium treated successfully with ECT.

Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

International Nuclear Information System (INIS)

Berman, Abigail T.; James, Sara St.; Rengan, Ramesh

2015-01-01

Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT), through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC), as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning

High-Flow Nasal Cannula versus Conventional Oxygen Therapy in Children with Respiratory Distress.

Science.gov (United States)

Sitthikarnkha, Punthila; Samransamruajkit, Rujipat; Prapphal, Nuanchan; Deerojanawong, Jitladda; Sritippayawan, Suchada

2018-05-01

The aim of this study is to determine the clinical efficacy of high-flow nasal cannula (HFNC) therapy compared with conventional oxygen therapy in children presented with respiratory distress. This was a randomized controlled study. Infants and children aged between 1 month to 5 years who were admitted to our tertiary referral center for respiratory distress (July 1, 2014 to March 31, 2015) and met the inclusion criteria were recruited. Infants and children hospitalized with respiratory distress were randomized into two groups of interventions. All clinical data, for example, respiratory score, pulse rate, and respiratory rate were recorded. The results were subsequently analyzed. A total of 98 respiratory distress children were enrolled during the study period. Only 4 children (8.2%) failed in HFNC therapy, compared with 10 children (20.4%) in conventional oxygen therapy group ( P = 0.09). After adjusted for body weight, underlying diseases, and respiratory distress score, there was an 85% reduction in the odds of treatment failure in HFNC therapy group (adjusted odds ratio 0.15, 95% confidence interval 0.03-0.66, P = 0.01). Most children in HFNC therapy group had significant improvement in clinical respiratory score, heart rate, and respiratory rate at 240, 360, and 120 min compared with conventional oxygen therapy ( P = 0.03, 0.04, and 0.03). HFNC therapy revealed a potential clinical advantage in management children hospitalized with respiratory distress compared with conventional respiratory therapy. The early use of HFNC in children with moderate-to-severe respiratory distress may prevent endotracheal tube intubation. TCTR 20170222007.

General Anaesthesia Protocols for Patients Undergoing Electroconvulsive Therapy

Science.gov (United States)

Narayanan, Aravind; Lal, Chandar; Al-Sinawi, Hamed

2017-01-01

Objectives This study aimed to review general anaesthesia protocols for patients undergoing electroconvulsive therapy (ECT) at a tertiary care hospital in Oman, particularly with regards to clinical profile, potential drug interactions and patient outcomes. Methods This retrospective study took place at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman. The electronic medical records of patients undergoing ECT at SQUH between January 2010 and December 2014 were reviewed for demographic characteristics and therapy details. Results A total of 504 modified ECT sessions were performed on 57 patients during the study period. All of the patients underwent a uniform general anaesthetic regimen consisting of propofol and succinylcholine; however, they received different doses between sessions, as determined by the treating anaesthesiologist. Variations in drug doses between sessions in the same patient could not be attributed to any particular factor. Self-limiting tachycardia and hypertension were periprocedural complications noted among all patients. One patient developed aspiration pneumonitis (1.8%). Conclusion All patients undergoing ECT received a general anaesthetic regimen including propofol and succinylcholine. However, the interplay of anaesthetic drugs with ECT efficacy could not be established due to a lack of comprehensive data, particularly with respect to seizure duration. In addition, the impact of concurrent antipsychotic therapy on anaesthetic dose and subsequent complications could not be determined. PMID:28417028

Tumor exosomes: cellular postmen of cancer diagnosis and personalized therapy.

Science.gov (United States)

Sharma, Aman; Khatun, Zamila; Shiras, Anjali

2016-02-01

Nanosized (30-150 nm) extracellular vesicles 'exosomes' are secreted by cells for intercellular communication during normal and pathological conditions. Exosomes carry biomacromolecules from cell-of-origin and, therefore, represent molecular bioprint of the cell. Tumor-derived exosomes or TDEx modulate tumor microenvironment by transfer of macromolecules locally as well as at distant metastatic sites. Due to their biological stability, TDEx are rich source of biomarkers in cancer patients. TDEx focused cancer diagnosis allows liquid biopsy-based tumor typing and may facilitate therapy response monitoring by developing novel exosomes diagnostics. Therefore, efficient and specific capturing of exosomes for subsequent amplification of the biomessages; for example, DNA, RNA, miRNA can reinvent cancer diagnosis. Here, in this review, we discuss advancements in exosomes isolation strategies, presence of exosomes biomarkers and importance of TDEx in gauging tumor heterogeneity for their potential use in cancer diagnosis, therapy.

Subsequent Reproductive Performance in Survivors of Complicated ...

African Journals Online (AJOL)

Objective To study the subsequent reproductive performance of women who had undergone complicated abortions. Materials and Methods Attempts were made to trace 299 survivors of complicated abortions from an earlier study. Their contact telephone numbers and addresses had been recorded at the time of initial ...

Patterns and Timing of Initial Relapse in Patients Subsequently Undergoing Transplantation for Hodgkin's Lymphoma

International Nuclear Information System (INIS)

Dhakal, Sughosh; Biswas, Tithi; Liesveld, Jane L.; Friedberg, Jonathan W.; Phillips, Gordon L.; Constine, Louis S.

2009-01-01

Purpose: To evaluate the patterns and timing of initial recurrence in patients with Hodgkin's lymphoma (HL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplantation to enhance our understanding of the natural history of this disease and its modern treatment strategies and to direct approaches to disease surveillance. Methods and Materials: The records of 69 patients with HL who had undergone high-dose chemotherapy with autologous stem cell transplantation in our center between May 1992 and June 2006 were analyzed. The initial diagnosis had been made between April 1982 and January 2005 at a median patient age of 33 years (range, 19-65). The patients were segregated according to the initial stage (Stage I-II vs. III-IV). Results: Early-stage HL patients developed a relapse at a median of 2.1 years (range, 0.5-10.3), with 91% of relapses at the initial disease site, 71% of which (65% overall) were only in previously involved sites. Advanced-stage HL patients developed a relapse at a median of 1.5 years (range, 0.6-10.5), with 97% at the initial site, 71% of which (69% overall) were only in previously involved sites. Single-site relapses occurred in 47% of early- vs. 26% of advanced-stage patients, and extranodal relapses occurred in 12% of early- vs. 31% of advanced-stage patients. Conclusions: Almost all patients with HL who develop relapse and subsequently undergo high-dose chemotherapy with autologous stem cell transplantation initially developed recurrence in previously involved disease sites. Early-stage HL relapses often occurred in single sites, and advanced-stage disease relapses were more likely in multiple and extranodal sites. The interval to recurrence was brief, suggesting that the frequency of screening should be the greatest in the early post-therapy years.

Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

Energy Technology Data Exchange (ETDEWEB)

Baum, R. P.; Przetak, C. [Zentralklinik Bad Berka, Clinic of Nuclear Medicine, Center for PET, Bad Berka (Germany)

2001-09-01

Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these.

Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

International Nuclear Information System (INIS)

Baum, R. P.; Przetak, C.

2001-01-01

Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these

Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

Science.gov (United States)

Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana

2015-03-01

There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

Non-surgical spinal decompression therapy: does the scientific literature support efficacy claims made in the advertising media?

Directory of Open Access Journals (Sweden)

Daniel Dwain M

2007-05-01

Full Text Available Abstract Background Traction therapy has been utilized in the treatment of low back pain for decades. The most recent incarnation of traction therapy is non-surgical spinal decompression therapy which can cost over $100,000. This form of therapy has been heavily marketed to manual therapy professions and subsequently to the consumer. The purpose of this paper is to initiate a debate pertaining to the relationship between marketing claims and the scientific literature on non-surgical spinal decompression. Discussion Only one small randomized controlled trial and several lower level efficacy studies have been performed on spinal decompression therapy. In general the quality of these studies is questionable. Many of the studies were performed using the VAX-D® unit which places the patient in a prone position. Often companies utilize this research for their marketing although their units place the patient in the supine position. Summary Only limited evidence is available to warrant the routine use of non-surgical spinal decompression, particularly when many other well investigated, less expensive alternatives are available.

SUBSEQUENT EVENTS AND THEIR IMPORTANCE IN DRAWING UP ANNUAL FINANCIAL STATEMENTS

Directory of Open Access Journals (Sweden)

Daniel Botez

2014-07-01

Full Text Available Subsequent events, called so because they are recorded after the closing date of financial year, must be recorded and taken into account in drawing up the financial statements. Some of them can fundamentally changing financial position of the entity or provide information to users absolutely necessary for their decisions. Accounting treatment in this situation is provided for by International Standard of Accounting ISA 10 “Events after the Reporting Period”, whose provisions are taken to a large extent in national accounting standards. For financial auditor, investigating how the subsequent events are presented in the financial statements shall constitute a procedural obligation. Auditor`s procedure is based on the provisions of an specific International Standard on Auditing, ISA 560 “Subsequent events”. He shall be required to satisfy itself that in the financial statements shall be presented all treatment and appropriate information concerning subsequent events.

Therapy for chronic myeloid leukemia: Past, present and future

International Nuclear Information System (INIS)

Tothova, E.

2012-01-01

Although chronic myeloid leukemia (CML) was probably first described in the early nineteenth century, there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 1960. Subsequent important landmarks were the recognition that the Ph chromosome results from a t(9;22) translocation and subsequently of BCR-ABL fusion gene. Between 1980 and 2000, allo grafting, despite the risks of morbidity and mortality, was the recommended initial treatment for younger patients with HLA-matched donors. Therapy has now been „revolutionized“ by the introduction on imatinib mesylate (IM), the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998. This paper will attempt to define approaches to management of the newly diagnosed patient with CML in chronic phase that are favored in 2012, but it is most probable these recommendations will need to be updated as further experience in gained with the use of TKI. (author)

Sports Mass Age Therapy on the Reduction of Delayed Onset Muscle Soreness of the Quadriceps Femoris

Directory of Open Access Journals (Sweden)

Boguszewski Dariusz

2014-12-01

Full Text Available Purpose. Massage therapy is one of most commonly applied treatments during athletic training. The aim of this study was to assess the effectiveness of sports massage therapy on reducing post-exercise quadriceps muscle soreness. Methods. A sample of 29 women aged 24-26 years was divided into an experimental group (n = 15 receiving classic sports massage therapy and a control group (n = 14 given no treatment. An exercise session consisting of five sets of deep squat jumps was administered after which lower limb power as assessed via the vertical jump test. Muscle soreness was assessed using the visual analogue scale (VAS and exercise intensity with the Borg Rating of Perceived Exertion Scale. Subsequent measurements of lower limb power and muscle soreness were performed 24, 48, 72 and 96 h after the exercise session. Differences between the measurements were assessed by the Friedman and least significant difference tests while between-group comparisons involved the Mann-Whitney U test. Results. The largest decrease in lower limb power was observed between the first measurement after the exercise session and 24 h later (p < 0.01. The smallest decrease in power was observed in the massage group. The highest levels of muscle soreness were noted 24 h post-exercise in the massage group and 48 h post-exercise in the control group. The experimental group showed a decrease in muscle soreness in each subsequent measurement, with the results close to zero on the VAS 96 h postexercise. Conclusions. Massage therapy quickened recovery and improved muscle efficiency post-exercise and may serve as an effective treatment of muscle soreness. The analgesic effect of massage suggests it should be widely applied in sport, physical therapy and rehabilitation.

12 CFR 226.20 - Subsequent disclosure requirements.

Science.gov (United States)

2010-01-01

... creditor need only disclose: (1) The unpaid balance of the obligation assumed. (2) The total charges imposed by the creditor in connection with the assumption. (3) The information required to be disclosed... creditor expressly agrees in writing with a subsequent consumer to accept that consumer as a primary...

Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

DEFF Research Database (Denmark)

Davis, Ian D; Xie, Wanling; Pezaro, Carmel

2017-01-01

BACKGROUND: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response. OBJECTIVE: To assess outcomes of 2L according to type...... of therapy and change in IMDC prognostic category. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined......% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p=0.03). CONCLUSIONS: Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy...

Cognitive-Behavioral Therapy for PTSD and Depression Symptoms Reduces Risk for Future Intimate Partner Violence among Interpersonal Trauma Survivors

Science.gov (United States)

Iverson, Katherine M.; Gradus, Jaimie L.; Resick, Patricia A.; Suvak, Michael K.; Smith, Kamala F.; Monson, Candice M.

2011-01-01

Objective: Women who develop symptoms of posttraumatic stress disorder (PTSD) and depression subsequent to interpersonal trauma are at heightened risk for future intimate partner violence (IPV) victimization. Cognitive-behavioral therapy (CBT) is effective in reducing PTSD and depression symptoms, yet limited research has investigated the…

Neutrons in active proton therapy. Parameterization of dose and dose equivalent

Energy Technology Data Exchange (ETDEWEB)

Schneider, Uwe; Haelg, Roger A. [Univ. of Zurich (Switzerland). Dept. of Physics; Radiotherapy Hirslanden AG, Aarau (Switzerland); Lomax, Tony [Paul Scherrer Institute, Villigen (Switzerland). Center for Proton Therapy

2017-08-01

One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85 cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138 MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160 MeV or 177 MeV instead of 138 MeV. For the neutron dose equivalent the increase is 8% and 57%. The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy.

Age at First Concussion Influences the Number of Subsequent Concussions.

Science.gov (United States)

Schmidt, Julianne D; Rizzone, Katherine; Hoffman, Nicole L; Weber, Michelle L; Jones, Courtney; Bazarian, Jeff; Broglio, Steven P; McCrea, Michael; McAllister, Thomas W

2018-04-01

Individuals who sustain their first concussion during childhood may be at greater risk of sustaining multiple concussions throughout their lifetime because of a longer window of vulnerability. This article aims to estimate the association between age at first concussion and number of subsequent concussions. A total of 23,582 collegiate athletes from 26 universities and military cadets from three military academies completed a concussion history questionnaire (65% males, age 19.9 ± 1.4 years). Participants self-reported concussions and age at time of each injury. Participants with a history of concussion (n = 3,647, 15.5%) were categorized as having sustained their first concussion during childhood (less than ten years old) or adolescence (≥10 and ≤18 years old). Poisson regression was used to model age group (childhood, adolescence) predicting the number of subsequent concussions (0, 1, 2+). A second Poisson regression was developed to determine whether age at first concussion predicted the number of subsequent concussions. Participants self-reporting their first concussion during childhood had an increased risk of subsequent concussions (rate ratio = 2.19, 95% confidence interval: 1.82, 2.64) compared with participants self-reporting their first concussion during adolescence. For every one-year increase in age at first concussion, we observed a 16% reduction in the risk of subsequent concussion (rate ratio = 0.84, 95% confidence interval: 0.82, 0.86). Individuals self-reporting a concussion at a young age sustained a higher number of concussions before age 18. Concussion prevention, recognition, and reporting strategies are of particular need at the youth level. Copyright © 2018 Elsevier Inc. All rights reserved.

Refractory primary immune thrombocytopenia with subsequent del(5q) MDS

DEFF Research Database (Denmark)

Bech Mortensen, Thomas; Frederiksen, Henrik; Marcher, Claus Werenberg

2017-01-01

A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological featu...

A review of empirically supported psychological therapies for mood disorders in adults

Science.gov (United States)

Hollon, Steven D.; Ponniah, Kathryn

2010-01-01

Background The mood disorders are prevalent and problematic. We review randomized controlled psychotherapy trials to find those that are empirically supported with respect to acute symptom reduction and the prevention of subsequent relapse and recurrence. Methods We searched the PsycINFO and PubMed databases and the reference sections of chapters and journal articles to identify appropriate articles. Results One hundred twenty-five studies were found evaluating treatment efficacy for the various mood disorders. With respect to the treatment of major depressive disorder (MDD), interpersonal psychotherapy (IPT), cognitive behavior therapy (CBT), and behavior therapy (BT) are efficacious and specific and brief dynamic therapy (BDT) and emotion-focused therapy (EFT) are possibly efficacious. CBT is efficacious and specific, mindfulness-based cognitive therapy (MBCT) efficacious, and BDT and EFT possibly efficacious in the prevention of relapse/recurrence following treatment termination and IPT and CBT are each possibly efficacious in the prevention of relapse/recurrence if continued or maintained. IPT is possibly efficacious in the treatment of dysthymic disorder. With respect to bipolar disorder, CBT and family-focused therapy (FFT) are efficacious and interpersonal social rhythm therapy (IPSRT) possibly efficacious as adjuncts to medication in the treatment of depression. Psycho-education (PE) is efficacious in the prevention of mania/hypomania (and possibly depression) and FFT is efficacious and IPSRT and CBT possibly efficacious in preventing bipolar episodes. Conclusions The newer psychological interventions are as efficacious as and more enduring than medications in the treatment of MDD and may enhance the efficacy of medications in the treatment of bipolar disorder. PMID:20830696

Managing post-therapy fatigue for cancer survivors using energy conservation training.

Science.gov (United States)

Yuen, Hon Keung; Mitcham, Maralynne; Morgan, Larissa

2006-01-01

This pilot study evaluated the effectiveness of energy conservation training to help post-therapy cancer survivors manage their fatigue. Twelve post-therapy cancer survivors were randomly assigned to an energy conservation training or usual care control (6 in each group). Participants in the intervention group received 1 to 2 hours of individual, face-to-face energy conservation training from an occupational therapist followed by once-a-week telephone monitoring sessions in the subsequent three weeks. Participants in the control group received standard care from their oncologist. Analysis of pre- and post-training data from the Piper Fatigue Scale (PFS) revealed significant reduction only in the sensory subscale of the PFS (Z = 2.21; p = 0.027) for the intervention group; but no significant reduction in the four subscale or total scores of the PFS for the control group. Findings demonstrate partial support for the effectiveness of energy conservation training in helping post-therapy cancer survivors manage their fatigue. Energy conservation training seems to be a viable strategy for managing cancer-related fatigue, though its efficacy is modest. Incorporating specific energy restoration strategies such as relaxation and meditation for future research may help advance the growing body of knowledge in symptom management for post-therapy cancer survivors.

Glycaemic adverse drug reactions from anti-neoplastics used in ...

African Journals Online (AJOL)

235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

Parental Views on Withdrawing Life-Sustaining Therapies in Critically Ill Children

Science.gov (United States)

Michelson, Kelly Nicole; Koogler, Tracy; Sullivan, Christine; del Pilar Ortega, María; Hall, Emily; Frader, Joel

2009-01-01

Objective To broaden existing knowledge of pediatric end-of-life decision making by exploring factors described by parents of patients in the pediatric intensive care unit (PICU) as important/influential if they were to consider withdrawing life-sustaining therapies. Design Quantitative and qualitative analysis of semi-structured one-on-one interviews. Setting The PICUs at 2 tertiary care hospitals. Participants English- or Spanish-speaking parents who were older than 17 years and whose child was admitted to the PICU for more than 24 hours to up to 1 week. Intervention Semi-structured one-on-one interviews. Results Forty of 70 parents (57%) interviewed said they could imagine a situation in which they would consider withdrawing life-sustaining therapies. When asked if specific factors might influence their decision making, 64% of parents said they would consider withdrawing life-sustaining therapies if their child were suffering; 51% would make such a decision based on quality-of-life considerations; 43% acknowledged the influence of physician-estimated prognosis in their decision; and 7% said financial burden would affect their consideration. Qualitative analysis of their subsequent comments identified 9 factors influential to parents when considering withdrawing life-sustaining therapies: quality of life, suffering, ineffective treatments, faith, time, financial considerations, general rejection of withdrawing life-sustaining therapies, mistrust/doubt toward physicians, and reliance on self/intuition. Conclusion Parents describe a broad range of views regarding possible consideration of withdrawing life-sustaining therapies for their children and what factors might influence such a decision. PMID:19884588

Proton Beam Therapy for Non-Small Cell Lung Cancer: Current Clinical Evidence and Future Directions

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Abigail T. Berman

2015-07-01

Full Text Available Lung cancer is the leading cancer cause of death in the United States. Radiotherapy is an essential component of the definitive treatment of early-stage and locally-advanced lung cancer, and the palliative treatment of metastatic lung cancer. Proton beam therapy (PBT, through its characteristic Bragg peak, has the potential to decrease the toxicity of radiotherapy, and, subsequently improve the therapeutic ratio. Herein, we provide a primer on the physics of proton beam therapy for lung cancer, present the existing data in early-stage and locally-advanced non-small cell lung cancer (NSCLC, as well as in special situations such as re-irradiation and post-operative radiation therapy. We then present the technical challenges, such as anatomic changes and motion management, and future directions for PBT in lung cancer, including pencil beam scanning.

Current perspectives on the use of ancillary materials for the manufacture of cellular therapies.

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Solomon, Jennifer; Csontos, Lynn; Clarke, Dominic; Bonyhadi, Mark; Zylberberg, Claudia; McNiece, Ian; Kurtzberg, Joanne; Bell, Rosemarie; Deans, Robert

2016-01-01

Continued growth in the cell therapy industry and commercialization of cell therapies that successfully advance through clinical trials has led to increased awareness around the need for specialized and complex materials utilized in their manufacture. Ancillary materials (AMs) are components or reagents used during the manufacture of cell therapy products but are not intended to be part of the final products. Commonly, there are limitations in the availability of clinical-grade reagents used as AMs. Furthermore, AMs may affect the efficacy of the cell product and subsequent safety of the cell therapy for the patient. As such, AMs must be carefully selected and appropriately qualified during the cell therapy development process. However, the ongoing evolution of cell therapy research, limited number of clinical trials and registered cell therapy products results in the current absence of specific regulations governing the composition, compliance, and qualification of AMs often leads to confusion by suppliers and users in this field. Here we provide an overview and interpretation of the existing global framework surrounding AM use and investigate some common misunderstandings within the industry, with the aim of facilitating the appropriate selection and qualification of AMs. The key message we wish to emphasize is that in order to most effectively mitigate risk around cell therapy development and patient safety, users must work with their suppliers and regulators to qualify each AM to assess source, purity, identity, safety, and suitability in a given application. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Requirements of exercise myocardial scintigraphy (EMS) using Tl-201 prior and subsequent to coronary revascularisation, based on the example of transluminal angioplasty

International Nuclear Information System (INIS)

Maul, F.D.; Hoer, G.; Standke, R.; Kober, G.; Klepzig, H. Jr.; Doerr, G.; Baum, R.P.; Happ, J.; Kaltenbach, M.; Frankfurt Univ.

1985-01-01

Quantitative exercise myocardial scintigraphy (EMS) using Thallium-201 in planar technique was applied in 128 patients prior and subsequent to transluminal coronary angioplasty. The overall sensitivity was 92%, and 88% for multivessel disease. In contrast to previous reports, the sensitivity for lesions of the posterior wall proved not inferior to that for lesions of the anterior wall: RCA-stenoses 92%; LCX-stenoses 100% and RIA-stenoses 93%. The specificity was found to be 88%, and the accuracy 92%. Myocardial ischaemia, as detected by EMS and ex. ECG, amounted to 84% and 72%, respectively in single vessel disease. The degree of ischaemia, which was measured semiquantitatively in terms of score, paralleled that of stenosis. The accuracy for localisation of anterior or posterior wall lesions was 92%. In unsuccessfully treated patients the results were completely reproducible (100%) both in terms of the decision 'CAD yes or no', and regarding the localisation of a myocardial lesion. The reproducibility for detection of myocardial ischaemia was 82%. Conclusion: In comparison with SPECT the quantitative planar EMS procedure using Tl-201 is the method of choice for the detection and assessment of ischaemia prior and subsequent to revascularisation therapy. (orig.) [de

Rocuronium-sugammadex use for electroconvulsive therapy in a hemodialysis patient: a case report.

Science.gov (United States)

Kurita, Shigeaki; Moriwaki, Katsuyuki; Shiroyama, Kazuhisa; Sanuki, Mikako; Toyota, Yukari; Takebayashi, Minoru

2016-01-01

Recently, rocuronium with subsequent use of sugammadex was proposed for electroconvulsive therapy (ECT) as an alternative to succinylcholine. Because sugammadex is cleared via the kidney with no metabolism, it is unknown that rocuronium-sugammadex use is safe in hemodialysis patients who received ECT. In this case report, we used rocuronium with subsequent administration of sugammadex in a 69-year-old female, hemodialysis patient, scheduled for ten ECT sessions for severe major depression. In the initial eight sessions, we tested the feasibility of rocuronium-sugammadex use for ECT. During the series of four ECT sessions, we measured plasma concentrations for the sum of sugammadex and sugammadex-rocuronium complex and observed whether possible residual sugammadex affected muscle relaxation during subsequent sessions of ECT. The results showed the feasibility of rocuronium-sugammadex use as muscle relaxants for ECT in patients undergoing hemodialysis. However, an accumulation of sugammadex did occur even after two sessions of hemodialysis, and residual sugammadex decreased the effect of the rocuronium given in the subsequent ECT sessions. Rocuronium-sugammadex was successfully utilized as muscle relaxants for ECT in this patient. Our experience in this case may indicate that if succinylcholine is contraindicated, rocuronium-sugammadex can be an alternative method for muscle relaxation during ECT in patients undergoing hemodialysis. When this rocuronium-sugammadex procedure is used, the effect of residual sugammadex after hemodialysis on the subsequently administered rocuronium should be considered.

Rehabilitation of oral function in head and neck cancer patients after radiotherapy with implant-retained dentures : Effects of hyperbaric oxygen therapy

NARCIS (Netherlands)

Schoen, P.J.; Raghoebar, G.M.; Bouma, J.; Reintsema, H.; Vissink, A.; Sterk, W.; Roodenburg, J.L.N.

Surgical treatment of malignancies in the oral cavity and subsequent radiotherapy often result in an anatomic and physiological oral condition unfavorable for prosthodontic rehabititation. The objective of this prospective study was to assess the effect of hyperbaric oxygen therapy on treatment

Additional effective dose by patients undergoing NAI-131 capsules therapy

Energy Technology Data Exchange (ETDEWEB)

Orlic, M.; Jovanovic, M.; Spasic Jokic, V.; Cuknic, O.; Ilic, Z.; Vranjes Djuric, S. [VINCA - Institute of Nuclear Sciences, Belgrade, Serbia and Montenegro (Yugoslavia)

2006-07-01

Capsules or solutions containing Na{sup 131}I are indicated for the therapy of some thyroid carcinomas such as functioning metastatic papillary or follicular carcinoma of the thyroid; and for the treatment of hyperthyroidism (diffuse toxic goiter and single or multiple toxic nodular goiter). The recommended dosage ranges of Na{sup 131}I capsules or solution for the therapy of the average patient (70 kg) are: (3.7-5.55) GBq for ablation of normal thyroid tissue; (3.7-7.4) GBq for subsequent treatments; a (148-370) MBq for hyperthyroidism. The purpose of this paper is to calculate effective dose as a result of iodine-131 capsules remaining in stomach before absorption starts. This result can determine the disadvantage of capsule versus solution containing sodium iodine-131 (Na{sup 131}I) in radionuclide therapy application from radiation protection point of view. The Monte Carlo code MCNP4b was used to model transport of gamma and beta particles emitted by radionuclide {sup 131}I treated as a point source at the bottom of stomach. Absorbed energy per unit transformation in stomach and surrounding organs has been calculated. (authors)

Target Therapies for Uterine Carcinosarcomas: Current Evidence and Future Perspectives

Directory of Open Access Journals (Sweden)

Salvatore Giovanni Vitale

2017-05-01

Full Text Available Carcinosarcomas (CS in gynecology are very infrequent and represent only 2–5% of uterine cancers. Despite surgical cytoreduction and subsequent chemotherapy being the primary treatment for uterine CS, the overall five-year survival rate is 30 ± 9% and recurrence is extremely common (50–80%. Due to the poor prognosis of CS, new strategies have been developed in the last few decades, targeting known dysfunctional molecular pathways for immunotherapy. In this paper, we aimed to gather the available evidence on the latest therapies for the treatment of CS. We performed a systematic review using the terms “uterine carcinosarcoma”, “uterine Malignant Mixed Müllerian Tumors”, “target therapies”, “angiogenesis therapy”, “cancer stem cell therapy”, “prognostic biomarker”, and “novel antibody-drug”. Based on our results, the differential expression and accessibility of epithelial cell adhesion molecule-1 on metastatic/chemotherapy-resistant CS cells in comparison to normal tissues and Human Epidermal Growth Factor Receptor 2 (HER2 open up new possibilities in the field of target therapy. Nevertheless, future investigations are needed to clarify the impact of these new therapies on survival rate and medium-/long-term outcomes.

Cutaneous Human Papillomavirus Infection and Development of Subsequent Squamous Cell Carcinoma of the Skin

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Shalaka S. Hampras

2016-01-01

Full Text Available The role of cutaneous human papillomavirus (HPV infection in the development of subsequent cutaneous squamous cell carcinoma (SCC is unknown. Pathologically confirmed cases of SCC (n=150 enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations of both, HPV seropositivity and HPV DNA positivity with subsequent SCC. The five year cumulative incidence of subsequent SCC was 72%. Seropositivity to cutaneous HPV was not associated with the risk of subsequent SCC (HR = 0.83, 95% CI = 0.41–1.67. Any beta HPV infection in EB was associated with reduced risk (HR = 0.30, 95% CI = 0.11–0.78 of subsequent SCC among cases who were positive for beta HPV DNA in tumor tissue. Infection with beta HPV type 2 (HR = 0.32, 95% CI = 0.12–0.86 in EB was associated with reduced risk of subsequent SCC among HPV DNA positive SCCs. In conclusion, beta HPV infection was inversely associated with the risk of subsequent SCC.

Self-Harm Intervention: Family Therapy (SHIFT), a study protocol for a randomised controlled trial of family therapy versus treatment as usual for young people seen after a second or subsequent episode of self-harm.

Science.gov (United States)

Wright-Hughes, Alexandra; Graham, Elizabeth; Farrin, Amanda; Collinson, Michelle; Boston, Paula; Eisler, Ivan; Fortune, Sarah; Green, Jonathan; House, Allan; Owens, David; Simic, Mima; Tubeuf, Sandy; Nixon, Jane; McCabe, Christopher; Kerfoot, Michael; Cottrell, David

2015-11-04

Self-harm is common in the community with a lifetime prevalence of 13 %. It is associated with an elevated risk of overall mortality and suicide. People who harm themselves are high users of public services. Estimates of the 1-year risk of repetition vary between 5 and 15 % per year. Currently, limited evidence exists on the effectiveness of clinical interventions for young people who engage in self-harm. Recent reviews have failed to demonstrate any effect on reducing repetition of self-harm among adolescents receiving a range of treatment approaches. Family factors are particularly important risk factors associated with fatal and non-fatal self-harm among children and adolescents. Family therapy focuses on the relationships, roles and communication patterns between family members, but there have been relatively few studies of specifically family-focused interventions with this population. The Self-Harm Intervention: Family Therapy (SHIFT) Trial was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (grant no. 07/33/01) following a commissioned call for this research. SHIFT is a pragmatic, phase III, multicentre, individually randomised, controlled trial comparing Family Therapy (FT) with treatment as usual (TAU) for adolescents aged 11 to 17 who have engaged in at least two episodes of self-harm. Both therapeutic interventions were delivered within the National Health Service (NHS) Child and Adolescent Mental Health Services (CAMHS) in England. Participants and therapists were, of necessity, aware of treatment allocation, but the researchers were blind to the allocations to allow unbiased collection of follow-up data. Primary outcome data (repetition of self-harm leading to hospital attendance 18 months post-randomisation) were collected from the Health and Social Care Information Centre (HSCIC), augmented by directed searches of medical records at Acute Trusts. Secondary outcome data (including suicidal intent

Syncope: causes, clinical evaluation, and current therapy.

Science.gov (United States)

Benditt, D G; Remole, S; Milstein, S; Bailin, S

1992-01-01

Syncope is a common clinical problem comprising the sudden loss of both consciousness and postural tone, with a subsequent spontaneous and relatively prompt recovery. Often it is difficult to differentiate a true syncopal spell from other conditions, such as seizure disorders, or from some simple accidents. Even more difficult is the identification of the cause of syncopal episodes. Nonetheless, establishing a definitive diagnosis ia an important task given the high risk of recurrent symptoms. Careful use of noninvasive and invasive cardiovascular studies (including electrophysiologic testing and tilt-table testing) along with selected hematologic, biochemical, and neurologic studies provides, in the majority of cases, the most effective strategy for obtaining a specific diagnosis and for directing therapy.

Eurythmy therapy in chronic disease: a four-year prospective cohort study

Directory of Open Access Journals (Sweden)

Willich Stefan N

2007-04-01

Full Text Available Abstract Background Many patients with chronic diseases use complementary therapies, often provided by their physicians. In Germany, several physician-provided complementary therapies have been reimbursed by health insurance companies as part of health benefit programs. In most of these therapies, the patient has a predominantly passive role. In eurythmy therapy, however, patients actively exercise specific movements with the hands, the feet or the whole body. The purpose of this study was to describe clinical outcomes in patients practising eurythmy therapy exercises for chronic diseases. Methods In conjunction with a health benefit program, 419 outpatients from 94 medical practices in Germany, referred to 118 eurythmy therapists, participated in a prospective cohort study. Main outcomes were disease severity (Disease and Symptom Scores, physicians' and patients' assessment on numerical rating scales 0–10 and quality of life (adults: SF-36, children aged 8–16: KINDL, children 1–7: KITA. Disease Score was documented after 0, 6 and 12 months, other outcomes after 0, 3, 6, 12, 18, 24, and (SF-36 and Symptom Score 48 months. Results Most common indications were mental disorders (31.7% of patients; primarily depression, fatigue, and childhood emotional disorder and musculoskeletal diseases (23.4%. Median disease duration at baseline was 3.0 years (interquartile range 1.0–8.5. Median number of eurythmy therapy sessions was 12 (interquartile range 10–19, median therapy duration was 119 days (84–188. All outcomes improved significantly between baseline and all subsequent follow-ups (exceptions: KITA Psychosoma in first three months and KINDL. Improvements from baseline to 12 months were: Disease Score from mean (standard deviation 6.65 (1.81 to 3.19 (2.27 (p Adverse reactions to eurythmy therapy occurred in 3.1% (13/419 of patients. No patient stopped eurythmy therapy due to adverse reactions. Conclusion Patients practising eurythmy therapy

A case of appropriate inappropriate device therapy: Hyperkalemia-induced ventricular oversensing

Science.gov (United States)

Oudit, Gavin Y; Cameron, Doug; Harris, Louise

2008-01-01

The present case describes a patient who received inappropriate, but potentially life-saving, therapy from her implantable cardioverter defibrillator (ICD) in the setting of acute hyperkalemia (plasma potassium concentration = 8 mM). Hyperkalemia was associated with the development of a slow sinusoidal ventricular tachycardia, at a rate of 100 beats/min to 125 beats/min (610 ms to 480 ms) in a patient who is pacemaker-dependent. There was associated fractionation of the ICD electrogram and T wave oversensing, leading to ventricular oversensing with resultant detection in the ventricular fibrillation rate zone. This was followed by shock therapy, even though the ventricular tachycardia rate was below the programmed detection rate of the ICD. The subsequent emergency treatment of the hyperkalemia normalized the electrogram, corrected the ventricular oversensing and arrhythmia, and restored rate-adaptive single-chamber ventricular pacing. PMID:18340383

Art Therapy: What Is Art Therapy?

Science.gov (United States)

... individual, couples, family, and group therapy formats. Art therapy is an effective treatment for people experiencing developmental, medical, educational, and social or psychological impairment. Individuals who benefit from art therapy include ...

The gene therapy revolution in ophthalmology.

Science.gov (United States)

Al-Saikhan, Fahad I

2013-04-01

The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber's Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red-green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable.

Protein Adsorption and Subsequent Fibroblasts Adhesion on Hydroxyapatite Nanocrystals

International Nuclear Information System (INIS)

Tagaya, Motohiro; Ikoma, Toshiyuki; Yoshioka, Tomohiko; Tanaka, Junzo; Takemura, Taro; Hanagata, Nobutaka

2011-01-01

Quartz crystal microbalance with dissipation (QCM-D) technique was employed for protein adsorption and subsequent fibroblast adhesion on hydroxyapatite (HAp) nanocrystals. The pre-adsorption of three proteins (albumin (BSA) or fibronectin (Fn) or collagen (Col)) and subsequent adsorption of fetal bovine serum (FBS), and the adhesion of fibroblasts on the surface were in situ monitored, and evaluated with the frequency shift (Δf) and dissipation energy shift (ΔD), and the viscoelastic change as ΔD-Δf plot. The Col adsorption showed larger Δf and ΔD values compared with BSA or Fn adsorption, and the subsequent FBS adsorption depended on the pre-adsorbed proteins. The ΔD-Δf plot of the cell adhesion also showed the different behaviour on the surfaces, indicating the process affected by cell-protein interactions. The confocal laser scanning microscope images of adherent cells showed the different morphology and pseudopod on the surfaces. The cells adhered on the surfaces modified with Fn and Col had the uniaxially expanded shape with fibrous pseudopods, while those modified with BSA had round shape. The different cell-protein interaction would cause the arrangement of extracellular matrix and cytoskeleton changes at the interfaces.

Protein Adsorption and Subsequent Fibroblasts Adhesion on Hydroxyapatite Nanocrystals

Energy Technology Data Exchange (ETDEWEB)

Tagaya, Motohiro; Ikoma, Toshiyuki; Yoshioka, Tomohiko; Tanaka, Junzo [Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, Tokyo, Tokyo 152-8550 (Japan); Takemura, Taro; Hanagata, Nobutaka, E-mail: tagaya.m.aa@m.titech.ac.jp [Biomaterials Center, National Institute for Materials Science, Tsukuba, Ibaraki 305-0047 (Japan)

2011-10-29

Quartz crystal microbalance with dissipation (QCM-D) technique was employed for protein adsorption and subsequent fibroblast adhesion on hydroxyapatite (HAp) nanocrystals. The pre-adsorption of three proteins (albumin (BSA) or fibronectin (Fn) or collagen (Col)) and subsequent adsorption of fetal bovine serum (FBS), and the adhesion of fibroblasts on the surface were in situ monitored, and evaluated with the frequency shift ({Delta}f) and dissipation energy shift ({Delta}D), and the viscoelastic change as {Delta}D-{Delta}f plot. The Col adsorption showed larger {Delta}f and {Delta}D values compared with BSA or Fn adsorption, and the subsequent FBS adsorption depended on the pre-adsorbed proteins. The {Delta}D-{Delta}f plot of the cell adhesion also showed the different behaviour on the surfaces, indicating the process affected by cell-protein interactions. The confocal laser scanning microscope images of adherent cells showed the different morphology and pseudopod on the surfaces. The cells adhered on the surfaces modified with Fn and Col had the uniaxially expanded shape with fibrous pseudopods, while those modified with BSA had round shape. The different cell-protein interaction would cause the arrangement of extracellular matrix and cytoskeleton changes at the interfaces.

Cell banking for regulatory T cell-based therapy: strategies to overcome the impact of cryopreservation on the Treg viability and phenotype.

Science.gov (United States)

Gołąb, Karolina; Grose, Randall; Placencia, Veronica; Wickrema, Amittha; Solomina, Julia; Tibudan, Martin; Konsur, Evelyn; Ciepły, Kamil; Marek-Trzonkowska, Natalia; Trzonkowski, Piotr; Millis, J Michael; Fung, John; Witkowski, Piotr

2018-02-09

The first clinical trials with adoptive Treg therapy have shown safety and potential efficacy. Feasibility of such therapy could be improved if cells are cryopreserved and stored until optimal timing for infusion. Herein, we report the evaluation of two cell-banking strategies for Treg therapy: 1) cryopreservation of CD4 + cells for subsequent Treg isolation/expansion and 2) cryopreservation of ex-vivo expanded Tregs (CD4 + CD25 hi CD127 lo/- cells). First, we checked how cryopreservation affects cell viability and Treg markers expression. Then, we performed Treg isolation/expansion with the final products release testing. We observed substantial decrease in cell number recovery after thawing and overnight culture. This observation might be explained by the high percentage of necrotic and apoptotic cells found just after thawing. Furthermore, we noticed fluctuations in percentage of CD4 + CD25 hi CD127 - and CD4 + FoxP3 + cells obtained from cryopreserved CD4 + as well as Treg cells. However, after re-stimulation Tregs expanded well, presented a stable phenotype and fulfilled the release criteria at the end of expansions. Cryopreservation of CD4 + cells for subsequent Treg isolation/expansion and cryopreservation of expanded Tregs with re-stimulation and expansion after thawing, are promising solutions to overcome detrimental effects of cryopreservation. Both of these cell-banking strategies for Treg therapy can be applied when designing new clinical trials.

Preliminary design of the database and registration system for the national malignant tumor interventional therapy

International Nuclear Information System (INIS)

Hu Di; Zeng Jinjin; Wang Jianfeng; Zhai Renyou

2010-01-01

Objective: This research is one of the sub-researches of 'The comparative study of the standards of interventional therapies and the evaluation of the long-term and middle-term effects for common malignant tumors', which is one of the National Key Technologies R and D Program in the eleventh five-year plan. Based on the project,the authors need to establish an international standard in order to set up the national tumor interventional therapy database and registration system. Methods: By using the computing programs of downloading software, self-management and automatic integration, the program was written by the JAVA words. Results: The database and registration system for the national tumor interventional therapy was successfully set up, and it could complete both the simple and complex inquiries. The software worked well through the initial debugging. Conclusion: The national tumor interventional therapy database and registration system can not only precisely tell the popularizing rate of the interventional therapy nationwide, compare the results of different methods, provide the latest news concerning the interventional therapy, subsequently promote the academic exchanges between hospitals, but also help us get the information about the distribution of the interventional physicians, the consuming quantity and variety of the interventional materials, so the medical costs can be reduced. (authors)

Effect of skipping breakfast on subsequent energy intake.

Science.gov (United States)

Levitsky, David A; Pacanowski, Carly R

2013-07-02

The objective was to examine the effect of consuming breakfast on subsequent energy intake. Participants who habitually ate breakfast and those who skipped breakfast were recruited for two studies. Using a randomized crossover design, the first study examined the effect of having participants consume either (a) no breakfast, (b) a high carbohydrate breakfast (335 kcals), or (c) a high fiber breakfast (360 kcals) on three occasions and measured ad libitum intake at lunch. The second study again used a randomized crossover design but with a larger, normal carbohydrate breakfast consumed ad libtum. Intake averaged 624 kcals and subsequent food intake was measured throughout the day. Participants ate only foods served from the Cornell Human Metabolic Research Unit where all foods were weighed before and after consumption. In the first study, neither eating breakfast nor the kind of breakfast consumed had an effect on the amount consumed at lunch despite a reduction in hunger ratings. In the second study, intake at lunch as well as hunger ratings were significantly increased after skipping breakfast (by 144 kcal), leaving a net caloric deficit of 408 kcal by the end of the day. These data are consistent with published literature demonstrating that skipping a meal does not result in accurate energy compensation at subsequent meals and suggests that skipping breakfast may be an effective means to reduce daily energy intake in some adults. Copyright © 2013 Elsevier Inc. All rights reserved.

75 FR 50880 - TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech Therapy

Science.gov (United States)

2010-08-18

... 0720-AB36 TRICARE: Non-Physician Referrals for Physical Therapy, Occupational Therapy, and Speech... referrals of beneficiaries to the Military Health System for physical therapy, occupational therapy, and... practitioners will be allowed to issue referrals to patients for physical therapy, occupational therapy, and...

Ventilation therapy for patients suffering from obstructive lung diseases.

Science.gov (United States)

Jungblut, Sven A; Heidelmann, Lena M; Westerfeld, Andreas; Frickmann, Hagen; Körber, Mareike K; Zautner, Andreas E

2014-01-01

Severe bronchial obstruction due to one of the major pulmonary diseases: asthma, COPD, or emphysema often requires mechanical ventilation support. Otherwise, patients are at risk of severe hypooxygenation with consecutive overloading and dilatation of the right cardiac ventricle with subsequent failure. This review focuses on how to manage a calculated ventilation therapy of patients suffering from bronchial obstruction and relevant patents. Options and pitfalls of invasive and non-invasive ventilation in the intensive care setting regarding clinical improvement and final outcome are discussed. The non-invasive ventilation is very efficient in treating acute or chronic respiratory failure in COPD patients and is capable of shortening the duration of hospitalization. Further non-invasive ventilation can successfully support the weaning after a long-lasting ventilation therapy and improve the prognosis of COPD patients. "Permissive hypercapnia" is unequivocally established in invasive ventilation therapy of severe bronchial obstruction in situations of limited ventilation. When intrinsic positive end-expiratory pressure (PEEP) and elevated airways resistance are present PEEP may be useful although external-PEEP application relieves over-inflation only in selected patients with airway obstruction during controlled mechanical ventilation. Upper limit of airways peak pressure used in "protective ventilation" of adult respiratory distress syndrome (ARDS) patients can be exceeded under certain circumstances.

Fluid Therapy: Double-Edged Sword during Critical Care?

Science.gov (United States)

Benes, Jan; Kirov, Mikhail; Kuzkov, Vsevolod; Lainscak, Mitja; Molnar, Zsolt; Voga, Gorazd; Monnet, Xavier

2015-01-01

Fluid therapy is still the mainstay of acute care in patients with shock or cardiovascular compromise. However, our understanding of the critically ill pathophysiology has evolved significantly in recent years. The revelation of the glycocalyx layer and subsequent research has redefined the basics of fluids behavior in the circulation. Using less invasive hemodynamic monitoring tools enables us to assess the cardiovascular function in a dynamic perspective. This allows pinpointing even distinct changes induced by treatment, by postural changes, or by interorgan interactions in real time and enables individualized patient management. Regarding fluids as drugs of any other kind led to the need for precise indication, way of administration, and also assessment of side effects. We possess now the evidence that patient centered outcomes may be altered when incorrect time, dose, or type of fluids are administered. In this review, three major features of fluid therapy are discussed: the prediction of fluid responsiveness, potential harms induced by overzealous fluid administration, and finally the problem of protocol-led treatments and their timing.

Bee sting therapy-induced hepatotoxicity: A case report.

Science.gov (United States)

Alqutub, Adel Nazmi; Masoodi, Ibrahim; Alsayari, Khalid; Alomair, Ahmed

2011-10-27

The use of bee venom as a therapeutic agent for the relief of joint pains dates back to Hippocrates, and references to the treatment can be found in ancient Egyptian and Greek medical writings as well. Also known as apitherapy, the technique is widely used in Eastern Europe, Asia, and South America. The beneficial effects of bee stings can be attributed to mellitinin, an anti-inflammatory agent, known to be hundred times stronger than cortisone. Unfortunately, certain substances in the bee venom trigger allergic reactions which can be life threatening in a sensitized individual. Multiple stings are known to cause hemolysis, kidney injury, hepatotoxicity and myocardial infarction. The toxicity can be immediate or can manifest itself only weeks after the exposure. We describe hepatotoxicity in a 35-year-old female, following bee sting therapy for multiple sclerosis. She presented to our clinic 3 wk after therapy with a history of progressive jaundice. The patient subsequently improved, and has been attending our clinic now for the last 9 mo.

The Buffer Effect of Therapy Dog Exposure on Stress Reactivity in Undergraduate Students

Directory of Open Access Journals (Sweden)

Alexandra J. Fiocco

2017-06-01

Full Text Available Stress is an insidious health risk that is commonly reported among university students. While research suggests that dog exposure may facilitate recovery from a stress response, little is known about the buffer effect of dog exposure on the stress response to a future stressor. This study examined whether interaction with a therapy dog could reduce the strength of the physiological stress response when exposed to a subsequent stressor. Sixty-one university students were randomly assigned to either a therapy dog (TD, n = 31 or a no-dog control (C, n = 30 group. The stress response was measured by electrodermal activity (EDA in response to the Paced Auditory Serial Addition Test (PASAT. Participants also completed questionnaires that assessed pet attitude, general stress levels, and affect. Analyses of covariance (ANCOVAs showed that increase in EDA was significantly more pronounced in the C group than in the TD group (p < 0.01. Pet attitudes did not modulate the buffer effect of therapy dog exposure. Results suggest that therapy dog exposure may buffer the stress response in university students, which has implications for the promotion of a viable stress management program on university campuses.

Testosterone Responders to Continuous Androgen Deprivation Therapy Show Considerable Variations in Testosterone Levels on Followup: Implications for Clinical Practice.

Science.gov (United States)

Sayyid, Rashid K; Sayyid, Abdallah K; Klaassen, Zachary; Fadaak, Kamel; Goldberg, Hanan; Chandrasekar, Thenappan; Ahmad, Ardalanejaz; Leao, Ricardo; Perlis, Nathan; Chadwick, Karen; Hamilton, Robert J; Kulkarni, Girish S; Finelli, Antonio; Zlotta, Alexandre R; Fleshner, Neil E

2018-01-01

We determined whether men on continuous androgen deprivation therapy who achieve testosterone less than 0.7 nmol/l demonstrate subsequent testosterone elevations during followup and whether such events predict worse oncologic outcomes. We evaluated a random, retrospective sample of 514 patients with prostate cancer treated with continuous androgen deprivation therapy in whom serum testosterone was less than 0.7 nmol/l at University Health Network between 2007 and 2016. Patients were followed from the date of the first testosterone measurement of less than 0.7 nmol/l to progression to castrate resistance, death or study period end. Study outcomes were the development of testosterone elevations greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, and progression to a castrate resistant state. Survival curves were constructed to determine the rate of testosterone elevations. Multivariate Cox regression analysis was done to assess whether elevations predicted progression to castrate resistance. Median patient age was 74 years and median followup was 20.3 months. Within 5 years of followup 82%, 45% and 18% of patients had subsequent testosterone levels greater than 0.7, greater than 1.1 and greater than 1.7 nmol/l, respectively. In 96% to 100% of these patients levels less than 0.7 nmol/l were subsequently reestablished within 5 years. No patient baseline characteristic was associated with elevations and elevations were not a significant predictor of progression to a castrate resistant state. Men on continuous androgen deprivation therapy in whom initial testosterone is less than 0.7 nmol/l frequently show subsequent elevations in serum testosterone. Such a development should not trigger an immediate response from physicians as these events are prognostically insignificant with regard to oncologic outcomes. Levels are eventually reestablished at less than 0.7 nmol/l. Copyright © 2018 American Urological Association Education and Research, Inc. Published by

Antiplatelet Therapy for Stable Coronary Artery Disease in Atrial Fibrillation Patients Taking an Oral Anticoagulant A Nationwide Cohort Study

DEFF Research Database (Denmark)

Lamberts, M.; Gislason, G. H.; Lip, G. Y. H.

2014-01-01

therapy to vitamin K antagonist (VKA) in atrial fibrillation patents with stable coronary artery disease. Methods and Results Atrial fibrillation patients with stable coronary artery disease (defined as 12 months from an acute coronary event) between 2002 and 2011 were identified. The subsequent risk...... of cardiovascular events and serious bleeding events (those that required hospitalization) was examined with adjusted Cox regression models according to ongoing antithrombotic therapy. A total of 8700 patients were included (mean age, 74.2 years; 38% women). During a mean follow-up of 3.3 years, crude incidence...

A prospective phase II study

DEFF Research Database (Denmark)

Grønberg, Bjørn H; Bremnes, Roy M; Aasebø, Ulf

2009-01-01

, anemia was observed in 2 (6%) patients, leukopenia in 6 (18%), granulocytopenia in 9 (27%) and thrombocytopenia in 3 (9%). Febrile neutropenia occurred in 6 (18%) patients. There were no treatment related deaths. CONCLUSION: High-dose pemetrexed monotherapy to patients with recurrent SCLC yielded...

Women's decision making and experience of subsequent pregnancy following stillbirth.

Science.gov (United States)

Lee, Louise; McKenzie-McHarg, Kirstie; Horsch, Antje

2013-01-01

This study sought to increase understanding of women's thoughts and feelings about decision making and the experience of subsequent pregnancy following stillbirth (intrauterine death after 24 weeks' gestation). Eleven women were interviewed, 8 of whom were pregnant at the time of the interview. Modified grounded theory was used to guide the research methodology and to analyze the data. A model was developed to illustrate women's experiences of decision making in relation to subsequent pregnancy and of subsequent pregnancy itself. The results of the current study have significant implications for women who have experienced stillbirth and the health professionals who work with them. Based on the model, women may find it helpful to discuss their beliefs in relation to healing and health professionals to provide support with this in mind. Women and their partners may also benefit from explanations and support about the potentially conflicting emotions they may experience during this time. © 2013 by the American College of Nurse-Midwives.

Rare metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes: A case report and literature review.

Science.gov (United States)

Cai, Changjing; Shen, Hong; Liu, Wenqiang; Ma, Junli; Zhang, Yan; Yin, Ling; Li, Jindong; Shen, Liangfang; Zeng, Shan

2017-11-01

Thyroid metastasis from nasopharyngeal carcinoma is rare. Metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes hasn't been reported before. We want to share our experience about the treatment choice. A 27-year-old man was diagnosed with nasopharyngeal nonkeratinizing carcinoma in August 2004. In March 2013 he underwent a thyroid carcinoma radical operation, and histological examination revealed metastasis to the thyroid gland from nasopharyngeal carcinoma. An 18F-FDG-PET/CT scan and biopsy showed metastatic abdominal lymph nodes of nasopharyngeal carcinoma in April 2015. A 27-year-old man was diagnosed with metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes. The patient was treated with concurrent chemotherapy and radiotherapy for nasopharyngeal carcinoma and metastasis to the thyroid gland. The metastases to the abdominal lymph nodes received chemotherapy. After 6 cycles of chemotherapy with gemcitabine, cisplatin, and 5-fluorouracil for metastasis to the abdominal lymph nodes, the patient is currently asymptomatic with stable disease and improved quality of life. The treatment choice for metastasis of nasopharyngeal carcinoma depends on the clinical disease extent, and surgery and/or chemo-radiation therapy must be drafted to the individual patient in order to improve the prognosis and quality of life.

Risk of subsequent gastrointestinal cancer among childhood cancer survivors : A systematic review

NARCIS (Netherlands)

Teepen, Jop C.; de Vroom, Suzanne L.; van Leeuwen, Flora E.; Tissing, Wim J.; Kremer, Leontien C.; Ronckers, Cecile M.

Background: Childhood cancer survivors (CCS) are at increased risk of developing subsequent malignant neoplasms, including gastrointestinal (GI) cancer. We performed a systematic review to summarize all available literature on the risk of, risk factors for, and outcome after subsequent GI cancer

Mechanisms of change in cognitive therapy for major depressive disorder in the community mental health setting.

Science.gov (United States)

Crits-Christoph, Paul; Gallop, Robert; Diehl, Caroline K; Yin, Seohyun; Gibbons, Mary Beth Connolly

2017-06-01

This study examined the relation of change in theory-relevant cognitive variables to depressive symptom change over the course of cognitive therapy, as well as the specificity of change mechanisms to cognitive therapy as compared with dynamic therapy. There were 237 adult outpatients who were randomized to either cognitive (n = 119) or dynamic (n = 118) therapy for major depressive disorder in a community mental health setting. Assessments of compensatory skills (Ways of Responding Community Version and Self-Report Version), dysfunctional attitudes (Dysfunctional Attitudes Scale), and depressogenic schemas (Psychological Distance Scaling Task) were obtained at baseline and months 1, 2, and 5 following baseline. Primary outcome was measured using the Hamilton Rating Scale for Depression. Across both therapy conditions, change in all 3 cognitive domains was associated with concurrent change in depressive symptoms. After controlling for other cognitive variables, increased interconnectedness of the positive achievement-related schema was significantly associated with concurrent symptom change in cognitive (rp = .26, p therapy (rp = .08, p = .29). Increases in positive compensatory skills were associated with subsequent change in depressive symptoms in cognitive therapy (rp = -.36, p = .003), but not in dynamic therapy (rp = .11, p = .386). Results provide support for the compensatory skills model of cognitive therapy (CT) within a community mental health setting. Additional research is necessary to understand other possible mechanisms of change in CT in the community setting. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

THE STRATEGY OF ANTIMICROBIAL THERAPY OF ACUTE UNCOMPLICATED PYELONEPHRITIS FROM THE POSITION OF ETIOLOGICAL DATA

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A. D. Kaprin

2015-01-01

Full Text Available Abstract:Acute pyelonephritis is one of the common diseases both in outpatient and in the hospital practice. The leading causative agent of this disease is E. coli. Obstructive uropathy, foreign body, vesicoureteral reflux, sexual activity, use of local contraceptives contribute to the upward development of urinary infection. The goals of antimicrobial therapy for acute uncomplicated pyelonephritis are: relief of symptoms, restoration of social activity, prevention of complications and relapse prevention. The choice of an antimicrobial agent in most cases is carried out empirically based on the data on the dominant pathogens and their regional resistance. In acute uncomplicated pyelonephritis duration of antimicrobial therapy should be 7–14 days. The drugs of choice for treatment of acute uncomplicated pyelonephritis non-severe in adults are ciprofloxacin and levofloxacin, ceftibuten and cefixime. Patients with acute uncomplicated pyelonephritis severe emergency hospitalization is shown in urological outpatient and parenteral antimicrobial therapy (carbapenems or protected aminopenicillins combined with or without amikacin with subsequent conversion to oral drugs and infusion therapy.

Safety and efficacy of targeted hyperthermia treatment utilizing gold nanorod therapy in spontaneous canine neoplasia.

Science.gov (United States)

Schuh, Elizabeth M; Portela, Roberta; Gardner, Heather L; Schoen, Christian; London, Cheryl A

2017-10-02

Hyperthermia is an established anti-cancer treatment but is limited by tolerance of adjacent normal tissues. Parenteral administration of gold nanorods (NRs) as a photosensitizer amplifies the effects of hyperthermia treatment while sparing normal tissues. This therapy is well tolerated and has demonstrated anti-tumor effects in mouse models. The purpose of this phase 1 study was to establish the safety and observe the anti-tumor impact of gold NR enhanced (plasmonic) photothermal therapy (PPTT) in client owned canine patients diagnosed with spontaneous neoplasia. Seven dogs underwent gold NR administration and subsequent NIR PPTT. Side effects were mild and limited to local reactions to NIR laser. All of the dogs enrolled in the study experienced stable disease, partial remission or complete remission. The overall response rate (ORR) was 28.6% with partial or complete remission of tumors at study end. PPTT utilizing gold nanorod therapy can be safely administered to canine patients. Further studies are needed to determine the true efficacy in a larger population of canine cancer patients and to and identify those patients most likely to benefit from this therapy.

Efficacy of chemotherapy after hormone therapy for hormone receptor-positive metastatic breast cancer.

Science.gov (United States)

Mori, Ryutaro; Nagao, Yasuko

2014-01-01

According to the guidelines for metastatic breast cancer, hormone therapy for hormone receptor-positive metastatic breast cancer without life-threatening metastasis should be received prior to chemotherapy. Previous trials have investigated the sensitivity of chemotherapy for preoperative breast cancer based on the efficacy of neoadjuvant hormone therapy. In this retrospective study, we investigated the efficacy of chemotherapy for metastatic breast cancer in hormone therapy-effective and hormone therapy-ineffective cases. Patients who received chemotherapy after hormone therapy for metastatic breast cancer between 2006 and 2013 at our institution were investigated. A total of 32 patients received chemotherapy after hormone therapy for metastatic breast cancer. The median patient age was 59 years, and most of the primary tumors exhibited a T2 status. A total of 26 patients had an N(+) status, while 7 patients had human epidermal growth factor receptor 2-positive tumors. A total of 13 patients received clinical benefits from hormone therapy, with a rate of clinical benefit of subsequent chemotherapy of 30.8%, which was not significantly different from that observed in the hormone therapy-ineffective patients (52.6%). A total of 13 patients were able to continue the hormone therapy for more than 1 year, with a rate of clinical benefit of chemotherapy of 38.5%, which was not significantly different from that observed in the short-term hormone therapy patients (47.4%). The luminal A patients were able to continue hormone therapy for a significantly longer period than the non-luminal A patients (median survival time: 17.8 months vs 6.35 months, p = 0.0085). However, there were no significant differences in the response to or duration of chemotherapy. The efficacy of chemotherapy for metastatic breast cancer cannot be predicted based on the efficacy of prior hormone therapy or tumor subtype, and clinicians should administer chemotherapy in all cases of

Development of liposomal pemetrexed for enhanced therapy against multidrug resistance mediated by ABCC5 in breast cancer

OpenAIRE

Bai,Fang; Yin,You; Chen,Ting; Chen,Jihui; Ge,Meixin; Lu,Yunshu; Xie,Fangyuan; Zhang,Jian; Wu,Kejin; Liu,Yan

2018-01-01

Fang Bai,1–3,* You Yin,4,* Ting Chen,1,* Jihui Chen,1 Meixin Ge,2 Yunshu Lu,2 Fangyuan Xie,5 Jian Zhang,1 Kejin Wu,3 Yan Liu1,6 1Department of Pharmacy, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 2Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, 3Department of Breast Surgery, Obstetrics and Gynaecology Hospital, Fudan University, Shanghai, 4Department of Neurology, Changzheng...

Graves' ophthalmopathy and 131I therapy

International Nuclear Information System (INIS)

Marcocci, C.; Bartalena, L.; Tanda, M.L.; Manetti, L.; Dell'Unto, E.; Mazzi, B.; Rocchi, R.; Barbesino, G.; Pinchera, A.

1999-01-01

Graves' ophthalmopathy is an autoimmune process initiated and maintained by antigen(s) shared by the thyroid and the orbit. A matter of argument concerns the choice of the method of treatment for Graves' hyperthyroidism when clinically evident ophthalmopathy is present. Restoration of euthyroidism appears to be beneficial for ophthalmopathy. On the other hand the continuing disease activity associated with the recurrence of hyperthyroidism appears to adversely affect the course of ophthalmopathy. For these reasons it is our opinion that in patients with Graves' hyperthyroidism and ophthalmopathy the permanent control of thyroid hyper function by ablation of thyroid tissue should be obtained by radioiodine therapy or thyroidectomy. The rationale for an ablative strategy is the following: i) permanent control of hyperthyroidism avoids exacerbations of eye disease associated with recurrence of hyperthyroidism; i i) hypothyroidism, which follows thyroid tissue ablation, should be regarded as a therapeutic end point rather than as an undesirable result; iii) ablation of thyroid tissue may result in the removal of both the thyroid-orbit cross-reacting antigen(s) and the major source of thyroid-auto reactive lymphocytes. The relationship between radioiodine therapy and the course of GO is a matter of controversy, and some authors have suggested that radioiodine administration ma be associated with a worsening of preexisting ophthalmopathy. This was not observed when radioiodine treatment was associated with a 3-month oral course of prednisone. The development or progression of GO after radioiodine therapy might be due to the release of thyroid antigens following radiation injury and to subsequent exacerbations of autoimmune reactions directed towards antigens shared by the thyroid and the orbit. The view that radioiodine therapy may be associated with a progression of ophthalmopathy is not shared by some authors who claim that the apparent link between progression of

Early Angiographic Resolution of Cerebral Vasospasm with High Dose Intravenous Milrinone Therapy

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F. A. Zeiler

2015-01-01

Full Text Available Background. Treatment of symptomatic delayed cerebral ischemia (DCI after subarachnoid hemorrhage (SAH is difficult. Recent studies suggest intravenous (IV high dose milrinone as a potential therapy. The timing to angiographic response with this is unclear. Methods. We reviewed the chart of one patient admitted for SAH who developed symptomatic DCI and was treated with high dose IV milrinone. Results. A 66-year-old female was admitted with a Hunt and Hess clinical grade 4, World Federation of Neurological Surgeons (WFNS clinical grade 4, and SAH secondary to a left anterior choroidal artery aneurysm which was clipped. After bleed day 6, the patient developed symptomatic DCI. We planned for angioplasty of the proximal segments. We administered high dose IV milrinone bolus followed by continuous infusion which led to clinical improvement prior to angiography. The angiogram performed 1.5 hours after milrinone administration displayed resolution of the CT angiogram and MRI based cerebral vasospasm such that further intra-arterial therapy was aborted. She completed 6 days of continuous IV milrinone therapy, was transferred to the ward, and subsequently rehabilitated. Conclusions. High dose IV milrinone therapy for symptomatic DCI after SAH can lead to rapid neurological improvement with dramatic early angiographic improvement of cerebral vasospasm.

Predictors and outcomes of cardiac resynchronization therapy extended to the second generator.

Science.gov (United States)

Li, Xuping; Yang, Dachun; Kusumoto, Fred; Shen, Win-Kuang; Mulpuru, Siva; Zhou, Shenghua; Liang, Jinjun; Wu, Gang; Yang, Mei; Liu, Jin-Qu; Friedman, Paul A; Cha, Yong-Mei

2017-12-01

A proportion of patients who receive cardiac resynchronization therapy with defibrillator (CRT-D) live to receive a second generator. Controversy exists on whether an implantable cardioverter-defibrillator (ICD) should be offered to patients who have normalized or near-normalized left ventricular ejection fraction (LVEF) at the time of generator replacement (GR). The purpose of this study was to evaluate incidence of appropriate ICD therapy after CRT-D GR. This series involved 1026 consecutive patients who underwent CRT-D implant between January 1, 2002 and December 31, 2012. Echocardiography was assessed before the initial device implant and before GR. ICDs were monitored at our device clinic in person or remotely, or both. Of the cohort, 227 patients (22.1%) underwent CRT-D GR at our institution. Approximately 48% of the patients who received new CRT-D generators were no longer meeting the guidelines indication for ICD use at the time of GR. These patients received subsequent appropriate ICD therapies at a significantly lower rate than those with LVEF generator after GR. Improvement in LVEF after CRT-D GR is associated with significantly reduced incidence of appropriate ICD therapy. Ventricular arrhythmia is less likely to develop with normalized LVEF in nonischemic cardiomyopathy. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Radiation therapy and patient age in the survival from early-stage breast cancer

International Nuclear Information System (INIS)

Joslyn, Sue A.

1999-01-01

Purpose: To analyze the use of radiation therapy following local excision of invasive localized breast cancer and subsequent survival by 5-year age category. Methods: Data for 27,399 women diagnosed with localized stage of breast cancer and treated with local excision surgery from 1983 through 1992 were collected and provided by the national Surveillance, Epidemiology, and End Results (SEER) program. Use of radiation therapy was analyzed by race, ethnic background, geographic location, and age at diagnosis. Survival for women treated with local excision plus radiation therapy was compared to that of women treated with local excision alone for each 5-year age category. Results: Subjects in older age groups were significantly less likely (p < 0.001) to receive radiation following local excision compared to younger age groups. Statistically significant survival advantages were conferred on women receiving radiation therapy in each 5-year age category from age 35 to 84 years (ranging from p = 0.02 to p < 0.0001). Conclusion: While the use of radiation therapy following local excision of early-stage breast tumors drops significantly in older age groups, women aged 35-84 years receiving radiation therapy had significant reductions in mortality. These results did not appear to be influenced by the presence of mortal comorbid conditions. These results strongly suggest the need to consider carefully patient characteristics other than age in deciding the course of treatment for early-stage breast cancer

Catheter and Laryngeal Mask Endotracheal Surfactant Therapy: the CALMEST approach as a novel MIST technique.

Science.gov (United States)

Vannozzi, Ilaria; Ciantelli, Massimiliano; Moscuzza, Francesca; Scaramuzzo, Rosa T; Panizza, Davide; Sigali, Emilio; Boldrini, Antonio; Cuttano, Armando

2017-10-01

Neonatal respiratory distress syndrome (RDS) is a major cause of mortality and morbidity among preterm infants. Although the INSURE (INtubation, SURfactant administration, Estubation) technique for surfactant replacement therapy is so far the gold standard method, over the last years new approaches have been studied, i.e. less invasive surfactant administration (LISA) or minimally invasive surfactant therapy (MIST). Here we propose an originally modified MIST, called CALMEST (Catheter And Laryngeal Mask Endotracheal Surfactant Therapy), using a particular laryngeal mask as a guide for a thin catheter to deliver surfactant directly in the trachea. We performed a preliminary study on a mannequin and a subsequent in vivo pilot trial. This novel procedure is quick, effective and well tolerated and might represent an improvement in reducing neonatal stress. Ultimately, CALMEST offers an alternative approach that could be extremely useful for medical staff with low expertise in laryngoscopy and intubation.

Workplace bullying and subsequent health problems.

Science.gov (United States)

Nielsen, Morten Birkeland; Magerøy, Nils; Gjerstad, Johannes; Einarsen, Ståle

2014-07-01

Cross-sectional studies demonstrate that exposure to bullying in the workplace is positively correlated with self-reported health problems. However, these studies do not provide a basis to draw conclusions on the extent to which bullying leads to increased health problems or whether health problems increase the risk of being bullied. To provide better indications of a causal relationship, knowledge from prospective studies on the association between bullying in the workplace and health outcomes is therefore summarised. We conducted a systematic literature review of original articles from central literature databases on longitudinal associations between bullying in the workplace and health. Average associations between bullying and health outcomes are calculated using meta-analysis. A consistent finding across the studies is that exposure to bullying is significantly positively related to mental health problems (OR =1.68; 95% KI 1.35-2.09) and somatic symptoms (OR = 1.77; 95% KI 1.41-2.22) over time. Mental health problems are also associated with subsequent exposure to bullying (OR = 1.74; 95% KI 1.44-2.12). Bullying is positively related to mental health problems and somatic symptoms. The association between mental health problems and subsequent bullying indicates a self-reinforcing process between mental health and bullying. The methodological quality of the studies that were conducted is relatively sound. However, based on the existing knowledge base there are no grounds for conclusions regarding an unambiguous causal relationship between bullying and health.

Subsequent publication of oral and maxillofacial surgery meeting abstracts.

Science.gov (United States)

Rodriguez, Joseph L; Laskin, Daniel M

2012-05-01

Previous studies in various medical specialties have shown that fewer than 50% of abstracts presented at meetings are subsequently published. The purpose of the present study was to determine the publication rate of abstracts presented at the annual meetings of the American Association of Oral and Maxillofacial Surgeons. The titles and authors of the abstracts from all oral abstract session presentations and posters by American contributors were collected from the Final Programs of the American Association of Oral and Maxillofacial Surgeons annual meetings for 2006 to 2009. A PubMed search for published articles through December 2010 was then performed using the authors' names, abstract titles, and key words. A total of 311 abstract presentations were done at the 4 annual meetings. Of these, only 85 (24%) were subsequently published. No difference was found between abstracts from oral or poster presentations. Most of the articles were published in the Journal of Oral and Maxillofacial Surgery. Because of deficiencies that can occur in abstracts and the need to disseminate the information they contain, it is important to take the appropriate measures to ensure that full articles are subsequently published. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Humanistic therapies versus other psychological therapies for depression

Science.gov (United States)

Churchill, Rachel; Davies, Philippa; Caldwell, Deborah; Moore, Theresa HM; Jones, Hannah; Lewis, Glyn; Hunot, Vivien

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To examine the effectiveness and acceptability of all humanistic therapies compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of different humanistic therapy models (person-centred, gestalt, process-experiential, transactional analysis, existential and non-directive therapies) compared with all other psychological therapy approaches for acute depression.To examine the effectiveness and acceptability of all humanistic therapies compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, cognitive-behavioural) for acute depression. PMID:25278809

Pediatric hospital discharge interventions to reduce subsequent utilization: a systematic review.

Science.gov (United States)

Auger, Katherine A; Kenyon, Chén C; Feudtner, Chris; Davis, Matthew M

2014-04-01

Reducing avoidable readmission and posthospitalization emergency department (ED) utilization has become a focus of quality-of-care measures and initiatives. For pediatric patients, no systematic efforts have assessed the evidence for interventions to reduce these events. We sought to synthesize existing evidence on pediatric discharge practices and interventions to reduce hospital readmission and posthospitalization ED utilization. PubMed and the Cumulative Index to Nursing and Allied Health Literature. Studies available in English involving pediatric inpatient discharge interventions with at least 1 outcome of interest were included. We utilized a modified Cochrane Good Practice data extraction tool and assessed study quality with the Downs and Black tool. Our search identified a total of 1296 studies, 14 of which met full inclusion criteria. All included studies examined multifaceted discharge interventions initiated in the inpatient setting. Overall, 2 studies demonstrated statistically significant reductions in both readmissions and subsequent ED visits, 4 studies demonstrated statistically significant reductions in either readmissions or ED visits, and 2 studies found statistically significant increases in subsequent utilization. Several studies were not sufficiently powered to detect changes in either subsequent utilization outcome measure. Interventions that demonstrated reductions in subsequent utilization targeted children with specific chronic conditions, providing enhanced inpatient feedback and education reinforced with postdischarge support. Interventions seeking to reduce subsequent utilization should identify an individual or team to assume responsibility for the inpatient-to-outpatient transition and offer ongoing support to the family via telephone or home visitation following discharge. © 2013 Society of Hospital Medicine.

Gene therapy and radionuclides targeting therapy in mammary carcinoma

International Nuclear Information System (INIS)

Song Jinhua

2003-01-01

Breast carcinoma's gene therapy is a hotspot in study of the tumor's therapy in the recent years. Currently the major therapy methods that in the experimentative and primary clinical application phases include immunological gene therapy, multidrug resistance gene therapy, antisense oligonucleotide therapy and suicide gene therapy. The gene targeting brachytherapy, which is combined with gene therapy and radiotherapy has enhanced the killer effects of the suicide gene and nuclide in tumor cells. That has break a new path in tumor's gene therapy. The further study in this field will step up it's space to the clinical application

8. Therapeutic and Educational Potential of Combining Cognitive Behavioural Therapy and Art – Qualitative Analysis of a Case Study

Directory of Open Access Journals (Sweden)

Růžička Michal

2016-03-01

Full Text Available Cognitive behavioural psychotherapy is, just like other psychotherapeutic systems, of an eclectic nature. Should a therapist be successful across a wide range of issues, he/she needs to be adaptable, flexible and eclectic in terms of the techniques applied. Eclectically oriented therapists use a wide range of interventions; however, they adhere to individual theoretical structures. The aim of the paper is to point out the application of a combination of artistic activities within the system of the Cognitive behavioural therapy. For this purpose the paper presents a qualitative analysis of two case studies. We formulated the following research questions. Can the methods of combining the cognitive behavioural therapy and art accelerate the course of therapy? Can the methods of combining the cognitive behavioural therapy and art be perceived by the client as effective? The phenomenon investigated in the case study is a functional analysis of a client’s case and subsequent application of therapeutic and educational techniques of the Cognitive behavioural therapy and art. In both case studies it was demonstrated that the involvement of therapeutic elements accelerated the course of therapy. The clients in the research sample assessed the therapy as beneficial.

Fitness Change and Subsequent Academic Performance in Adolescents

Science.gov (United States)

Chen, Li-Jung; Fox, Kenneth R.; Ku, Po-Wen; Taun, Chih-Yang

2013-01-01

Background: This study examined the association between fitness change and subsequent academic performance in Taiwanese schoolchildren from 7th grade to 9th grade. Methods: The 7th graders from 1 junior high school district participated in this study (N=669). Academic performance was

Intensity-modulated radiation therapy: dynamic MLC (DMLC) therapy, multisegment therapy and tomotherapy. An example of QA in DMLC therapy

International Nuclear Information System (INIS)

Webb, S.

1998-01-01

Intensity-modulated radiation therapy will make a quantum leap in tumor control. It is the new radiation therapy for the new millennium. The major methods to achieve IMRT are: 1. Dynamic multileaf collimator (DMLC) therapy, 2. multisegment therapy, and 3. tomotherapy. The principles of these 3 techniques are briefly reviewed. Each technique presents unique QA issues which are outlined. As an example this paper will present the results of a recent new study of an important QA concern in DMLC therapy. (orig.) [de

Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage

DEFF Research Database (Denmark)

Ottosen, Tobias Pilgaard; Grijota, Miriam; Hansen, Morten Lock

2016-01-01

inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality......BACKGROUND AND PURPOSE: The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage...... and examined the impact of subsequent AT use on the long-term clinical outcome. METHODS: We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were...

The Process of Change in Cognitive Therapy for Depression when Combined with Antidepressant Medication: Predictors of Early Intersession Symptom Gains

Science.gov (United States)

Strunk, Daniel R.; Cooper, Andrew A.; Ryan, Elizabeth T.; DeRubeis, Robert J.; Hollon, Steven D.

2012-01-01

Objective: Previous studies of cognitive therapy (CT) for depression have examined therapist adherence and the therapeutic alliance as predictors of subsequent symptom change. However, little is known about these CT process variables when CT is delivered in combination with antidepressant medication. Method: In a sample of 176 depressed…

Radioiodine therapy in veterinary medicine: treatment of hyperthyroidism in a cat

International Nuclear Information System (INIS)

Reinartz, P.; Sabri, O.; Zimny, M.; Buell, U.

1999-01-01

A nine-year-old cat with symptoms of a distinct hyperthyroidism was presented at the University Hospital of the RWTH Aachen. The clinical symptoms as well as the diagnostic procedures performed at the hospital confirmed the diagnosis. After five weeks of thyreostatic medication a regular metabolism of the thyroid gland was established, followed by a radioiodine therapy with 70.3 MBq 131-iodine. Subsequently, the cat was hospitalized for two days before it could be released in good condition. Six weeks after treatment the former drastically reduced weight of the cat recovered to near normal. Even though the chemical analysis detected a discrete hyperthyroidism, clinical symptoms were no longer prominent. Three months after treatment, the final examination showed a regular metabolism of the thyroid gland without a specific thyroidal medication. The presented case illustrates that radioiodine therapy is a safe and efficient treatment of thyroidal dysfunctions in veterinary medicine. (orig.) [de

Adenocarcinoma of the lung with EGFR gene mutation and subsequent resistance mechanisms exploration: case report

Directory of Open Access Journals (Sweden)

Xu L

2017-09-01

Full Text Available Li Xu,1,2 Qian Z Wang,1,2 Lin Wu1,2 1Department of the Second Chest Medicine, Hunan Cancer Hospital, Changsha, Hunan, People’s Republic of China; 2Department of the Second Chest Medicine, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China Abstract: The treatment of lung cancer has made paradigm-shift advancements in the past decade with the development of therapies directed at specific genetic alterations, such as epidermal growth factor receptor (EGFR. Here, we present a rare case of lung adenocarcinoma harboring EGFR activating mutation and ALK overexpression. During the EGFR-tyrosine kinase inhibitors treatment, next-generation sequencing revealed phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathway amplifications in tumor specimen and subsequent T790M mutation via plasma circulating tumor DNA. In conclusion, this case illustrates the existence of concomitant resistance mechanisms and demonstrates that circulating tumor DNA can reflect tumor heterogeneity. Keywords: epidermal growth factor receptor, PI3K/Akt/mTOR pathway, T790M, next-generation sequencing, circulating tumor DNA

The effect of substitution therapy on symptoms in patients with hypothyroidism following treatment for laryngeal and hypopharyngeal carcinomas.

Science.gov (United States)

Lo Galbo, A M; Verdonck-De Leeuw, I M; Lips, P; Kuik, D J; Leemans, C R; De Bree, R

2013-08-01

Hypothyroidism is a well-known complication following treatment of laryngeal or hypopharyngeal carcinomas, and may cause various psychological and physical problems that negatively affect quality of life. The aim of this study was to evaluate the effect of substitution therapy on symptoms in patients with hypothyroidism. A study-specific questionnaire on physical and psychological problems (before and after substitution therapy) was sent to 70 patients who had been treated between 1977 and 2008 with clinical or subclinical hypothyroidism. Ninety-four percent returned the questionnaire. Symptoms on energy levels were reported most often (67% always tired and 70% lack of energy). Moodiness and emotional and physical symptoms were reported more often in substituted (sub)clinical hypothyroidism. Substitution therapy resulted in an improvement of energy (P = 0.013), sense of general interest and enjoyment (P = 0.022) and a reduction of puffy face (P = 0.041). Most symptoms in patients with thyroid dysfunction do not improve after substitution therapy. Nevertheless, due to its impact on health-related quality of life and the low burden of substitution therapy, screening for hypothyroidism and subsequent substitution therapy remains important.

Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

Science.gov (United States)

Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

2016-05-26

The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

SU-E-J-143: Short- and Near-Term Effects of Proton Therapy On Cerebral White Matter

Energy Technology Data Exchange (ETDEWEB)

Uh, J; Merchant, T; Ogg, R; Sabin, N; Hua, C [St. Jude Children' s Research Hospital, Memphis, TN (United States); Indelicato, D [University of Florida Proton Therapy Institute, Jacksonville, FL (United States)

2014-06-01

Purpose: To assess early effects of proton therapy on the structural integrity of cerebral white matter in relation to the subsequent near-term development of such effects. Methods: Sixteen children (aged 2–19 years) with craniopharyngioma underwent proton therapy of 54 Cobalt Gray Equivalent (CGE) in a prospective therapeutic trial. Diffusion tensor imaging (DTI) was performed at baseline before proton therapy and every 3 months thereafter. Tract-based spatial statics analysis of DTI data was performed to derive the fractional anisotropy (FA) and radial diffusivity (RD) in 26 volumes of interest (VOIs). The dose distributions were spatially normalized to identify VOIs prone to high doses. The longitudinal percentage changes of the FA and RD in these VOIs at 3 and 12 months from the baseline were calculated, and their relationships were evaluated. Results: The average dose was highest to the cerebral peduncle (CP), corticospinal tract (CST) in the pons, pontine crossing tract (PCT), anterior/posterior limbs of the internal capsule (ALIC/PLIC), and genu of the corpus callosum (GCC). It ranged from 33.3 GCE (GCC) to 49.7 GCE (CP). A mild but statistically significant (P<0.05) decline of FA was observed 3 months after proton therapy in all VOIs except the PLIC and ranged from −1.7% (ALIC) to −2.8% (PCT). A significant increase of RD was found in the CP (3.5%) and ALIC (2.1%). The average longitudinal change from the baseline was reduced at 12 months for most VOIs. However, the standard deviation increased, indicating that the temporal pattern varied individually. The follow-up measurements at 3 and 12 months correlated for the CP, CST, PCT, and GCC (P < 0.04). Conclusion: DTI data suggest early (3 months) effects of proton therapy on microstructures in the white matter. The subsequent follow-up indicated individual variation of the changes, which was partly implied by the early effects.

Unilateral hypoglossal nerve atrophy as a late complication of radiation therapy of head and neck carcinoma: a report of four cases and a review of the literature on peripheral and cranial nerve damages after radiation therapy

International Nuclear Information System (INIS)

Cheng, V.S.T.; Schulz, M.D.

1975-01-01

The case histories of four patients who developed hemiatrophy of the tongue from 3 to 9 years after a course of curative radiation therapy for carcinomas of the head and neck are presented. These patients were subsequently followed from 1 1 / 2 to 6 years without local recurrence of the tumor, distant metastasis, or involvement of other cranial nerves, indicative of only a unilateral hypoglossal nerve atrophy. A review of the literature showed that peripheral and cranial nerve damages after radiation therapy have been reported for the optic nerve, hypoglossal nerve, oculomotor nerve, abducens nerve, recurrent laryngeal nerve, brachial plexus nerves, and peripheral nerves of the extremities. Review of clinical and experimental data indicated that in most cases, the damages were probably caused by extensive connective tissue fibrosis around and infiltrating the nerve trunks. Three possible types of peripheral and cranial nerve damages after radiation therapy are identified. (U.S.)

Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer’s disease therapeutics

OpenAIRE

de la Monte, Suzanne M.

2012-01-01

Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer’s disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer’s, subsequent neurodegeneration might be prevented. ...

Is Clostridium difficile infection a risk factor for subsequent bloodstream infection?

Science.gov (United States)

Ulrich, Robert J; Santhosh, Kavitha; Mogle, Jill A; Young, Vincent B; Rao, Krishna

2017-12-01

Clostridium difficile infection (CDI) is a common nosocomial diarrheal illness increasingly associated with mortality in United States. The underlying factors and mechanisms behind the recent increases in morbidity from CDI have not been fully elucidated. Murine models suggest a mucosal barrier breakdown leads to bacterial translocation and subsequent bloodstream infection (BSI). This study tests the hypothesis that CDI is associated with subsequent BSI in humans. We conducted a retrospective cohort study on 1132 inpatients hospitalized >72 h with available stool test results for toxigenic C. difficile. The primary outcome was BSI following CDI. Secondary outcomes included 30-day mortality, colectomy, readmission, and ICU admission. Unadjusted and adjusted logistic regression models were developed. CDI occurred in 570 of 1132 patients (50.4%). BSI occurred in 86 (7.6%) patients. Enterococcus (14%) and Klebsiella (14%) species were the most common organisms. Patients with BSI had higher comorbidity scores and were more likely to be male, on immunosuppression, critically ill, and have a central venous catheter in place. Of the patients with BSI, 36 (42%) had CDI. CDI was not associated with subsequent BSI (OR 0.69; 95% CI 0.44-1.08; P = 0.103) in unadjusted analysis. In multivariable modeling, CDI appeared protective against subsequent BSI (OR 0.57; 95% CI 0.34-0.96; P = 0.036). Interaction modeling suggests a complicated relationship among CDI, BSI, antibiotic exposure, and central venous catheter use. In this cohort of inpatients that underwent testing for CDI, CDI was not a risk factor for developing subsequent BSI. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of therapeutic irradiation delivered in early childhood upon subsequent lung function

International Nuclear Information System (INIS)

Wohl, M.E.B.; Griscom, N.T.; Graggis, D.G.; Jaffe, N.

1975-01-01

To determine the long-term effects of therapeutic pulmonary irradiation and treatment with actinomycin D during a period of lung growth, 12 patients treated for Wilms' tumor metastatic to the lung and 8 patients treated for Wilms' tumor with no evidence of pulmonary metastases were studied 7 to 14 years after their initial tumor therapy. All patients had received irradiation to the tumor bed and treatment with actinomycin D. Group 1 had received a single course of bilateral pulmonary irradiation; group 2 had received additional pulmonary irradiation and/or thoracic surgery; group 3 had received no therapeutic irradiation directed primarily to the chest. Total lung capacity (TLC) averaged 71 percent of predicted value in group 1, 58 percent in group 2, and 94 percent in group 3. Diffusing capacity in groups 1 and 2 was reduced to the same extent as lung volume. Quasi-static pressure-volume relationships, studied in three of six patients in group 1, were within the normal range when lung volume was expressed as percentage of observed TLC. Airway resistance, evaluated by spirometry, maximum expiratory flow-volume curves, and resistance of the total respiratory system, was normal or reduced. The data support the hypothesis that therapeutic irradiation during a period of lung growth primarily affects the lung parenchyma and produces a decrease in subsequent size of both the lung and chest wall. No effect of actinomycin D alone upon the lung could be demonstrated

[Bendamustine-rituximab therapy is effective for transformed follicular lymphoma with significant expression of p53].

Science.gov (United States)

Kuroda, Hiroyuki; Jomen, Wataru; Miura, Shogo; Arihara, Yohei; Yamada, Michiko; Hirako, Tasuku; Abe, Tomoyuki; Sakurai, Tamaki; Fujii, Shigeyuki; Maeda, Masahiro; Fujita, Miri; Nagashima, Kazuo; Okagawa, Yutaka; Hoki, Toshifumi; Kato, Junji

2013-08-01

We describe a patient with transformed follicular lymphoma(FL), expressing p53 but remaining in complete remission(CR) due to bendamustine-rituximab(BR)therapy. She was a 64-year-old female diagnosed with stage IV FL(grade 3A)in July 2007 when she was admitted with right lower abdominal pain and body weight loss. Colonoscopy revealed Bauhin' valve lymphoma of the terminal ileum, and computed tomography(CT)scan showed lymphadenopathy, involving the cervical, mediastinal para-aortic lymph nodes and right tonsil. She received chemotherapy with eight courses of CHOP therapy with rituximab and achieved CR. Two and a half years later, mediastinal lymph node swelling relapsed, and ibritumomab tiuxetan therapy induced the second CR. After ten months, however, a third relapse occurred as a submucosal tumor(SMT)of the stomach. Gastric SMT biopsy showed diffuse large B cell lymphoma(DLBCL)transformation with immunohistochemical expression of p53. Although gastric SMT disappeared after radiotherapy, which achieved the third CR, lymph node swelling was detected again in the para-aortic and-iliac artery lymph nodes in September 2011. Subsequently, she was treated with five courses of BR therapy, because bendamustine had been reported to be effective for p53 gene-deficient B cell neoplasms. The therapy was successful and achieved the fourth CR, demonstrating that BR therapy was effective for p53-expressing DLBCL.

Measuring Motivation: Change Talk and Counter-Change Talk in Cognitive Behavioral Therapy for Generalized Anxiety

OpenAIRE

Lombardi, Diana R.; Button, Melissa; Westra, Henny A.

2013-01-01

How clients talk about change early in treatment has been found to be a potent predictor of their subsequent treatment success. Studies examining such client motivational language (arguments for and against change) have typically been conducted in the context of motivational interviewing for addictions. The present study examined the capacity of client motivational language to predict treatment outcomes in the context of cognitive behavioral therapy (CBT) for generalized anxiety. Client early...

Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother

DEFF Research Database (Denmark)

Lykke, Jacob A; Langhoff-Roos, Jens; Sibai, Baha M

2009-01-01

Minimal data exist concerning the relationship between hypertensive pregnancy disorders and various subsequent cardiovascular events and the effect of type 2 diabetes mellitus on these. In a registry-based cohort study, we identified women delivering in Denmark from 1978 to 2007 with a first...... pregnancy disorders are strongly associated with subsequent type 2 diabetes mellitus and hypertension, the latter independent of subsequent type 2 diabetes mellitus. The severity, parity, and recurrence of these hypertensive pregnancy disorders increase the risk of subsequent cardiovascular events....... for the development of type 2 diabetes mellitus. The end points were subsequent hypertension, ischemic heart disease, congestive heart failure, thromboembolic event, stroke, and type 2 diabetes mellitus. The risk of subsequent hypertension was increased 5.31-fold (range: 4.90 to 5.75) after gestational hypertension...

Physical Therapy and Occupational Therapy in Progeria

Science.gov (United States)

Physical Therapy and Occupational Therapy in Progeria Information for Families and Caretakers from The Progeria Research Foundation ... Inc. All rights reserved. Page 2 of 5 Physical and Occupational Therapy in Progeria Hutchinson-Gilford Progeria ...

Multisurface Interpersonal Assessment in a Cognitive-Behavioral Therapy Context.

Science.gov (United States)

Dawood, Sindes; Pincus, Aaron L

2016-01-01

The interpersonal paradigm of personality assessment provides a rich nomological net for describing and assessing constructs of interpersonal functioning. The aim of this article is to demonstrate for clinicians how the use of a multisurface interpersonal assessment (MSIA) battery can augment psychotherapy (e.g., cognitive-behavioral therapy). We present 2 clinical case examples and specify interpretative guidelines for MSIA that integrate multiple circumplex profiles (e.g., problems, traits, sensitivities, strengths, values, and efficacies) for each patient. Subsequently, we demonstrate how this approach provides a context to better understand patient symptoms and difficulties, and discuss how it can inform case conceptualization, treatment planning, and intervention.

Infant and child deaths: Parent concerns about subsequent pregnancies.

Science.gov (United States)

Brooten, Dorothy; Youngblut, JoAnne M; Hannan, Jean; Caicedo, Carmen; Roche, Rosa; Malkawi, Fatima

2015-12-01

Examine parents' concerns about subsequent pregnancies after experiencing an infant or child death (newborn to 18 years). Thirty-nine semistructured parent (white, black, Hispanic) interviews 7 and 13 months post infant/child death conducted in English and/or Spanish, audio-recorded, transcribed, and content analyzed. Mothers' mean age was 31.8 years, fathers' was 39 years; 11 parents were white, 16 black, and 12 Hispanic. Themes common at 7 and 13 months: wanting more children; fear, anxiety, scared; praying to God/God's will; thinking about/keeping the infant's/child's memory and at 7 months importance of becoming pregnant for family members; and at 13 months happy about a new baby. Parents who lost a child in neonatal intensive care unit (NICU) commented more than those who lost a child in pediatric intensive care unit (PICU). Black and Hispanic parents commented more on praying to God and subsequent pregnancies being God's will than white parents. Loss of an infant/child is a significant stressor on parents with documented negative physical and mental health outcomes. Assessing parents' subsequent pregnancy plans, recognizing the legitimacy of their fears about another pregnancy, discussing a plan should they encounter problems, and carefully monitoring the health of all parents who lost an infant/child is an essential practitioner role. ©2015 American Association of Nurse Practitioners.

Leukemia after therapy with alkylating agents for childhood cancer

International Nuclear Information System (INIS)

Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.

1987-01-01

The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates [relative risk (RR) = 14; 95% confidence interval (CI), 9-22]. The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents

Gestalt Therapy and Cognitive Therapy - Contrasts or Complementarities?

DEFF Research Database (Denmark)

Tønnesvang, Jan; Sommer, Ulla; Hammink, James

2010-01-01

The article investigates the relationship between crucial concepts and understandings in gestalt therapy and cognitive therapy aiming at discussing if and how they can be mutually enriching when considered as complementary parts in a more encompassing integrative therapeutic approach. It is argued...... that gestalt therapy, defined as a fieldtheoretical approach to the study of gestalt formation process, can complement the schema-based understanding and practice in cognitive therapy. The clinical benefits from a complementary view of the two approaches will be a wider scope of awareness toward individual...... between fundamental awareness work in gestalt therapy and the tendency within cognitive therapy toward incorporating mindfulness as a therapeutic tool. In the conclusion of the article, additional complementary points between the two approaches are outlined. Keywords: integrative therapy, gestalt...

Amifostine is a potent radioprotector of salivary glands in radioiodine therapy. Structural and ultrastructural findings

International Nuclear Information System (INIS)

Kutta, H.; Kampen, U.; Sagowski, C.; Brenner, W.; Bohuslavizki, K.H.; Paulsen, F.

2005-01-01

Background and purpose: salivary gland impairment following high-dose radioiodine treatment is well recognized. Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. This study investigates the radioprotective effects of amifostine in salivary glands of rabbits receiving high-dose radioiodine therapy so as to obtain deeper insight in changes on the cellular and ultrastructural level. Material and methods: a total of 20 rabbits were investigated. High-dose radioiodine therapy applying 1 GBq 131 I was performed in 16 animals. Eight of these 16 animals received 200 mg/m 2 body surface amifostine prior to high-dose radioiodine therapy. Four additional rabbits served as controls, two receiving amifostine, the other two no treatment at all. Subsequently, salivary glands (submandibular and parotid glands, respectively) of all animals were examined by light and transmission electron microscopy. Results: parenchymal damage of both parotid and submandibular glands, specially acinar structures comprising cell organelles and nuclei, of animals pretreated with amifostine was much less pronounced than in animals without amifostine pretreatment. Conclusion: the results indicate that parenchymal damage in salivary glands induced by high-dose radioiodine therapy can significantly be reduced by amifostine. Therefore, amifostine therapy may increase quality of life in patients with differentiated thyroid cancer after radioiodine treatment. (orig.)

Tritium sorption by cement and subsequent release

International Nuclear Information System (INIS)

Ono, F.; Yamawaki, M.

1995-01-01

In a fusion reactor or tritium-handling facilities, contamination of concrete by tritium and subsequent release from it to the reator or experimental room is a matter of problem for safe control of tritium and management of operational environment. In order to evaluate this tritium behavior, interaction of tritiated water with concrete or cement should be clarified. In the present study, HTO sorption and subsequent release from cement were experimentally studied.(1)Sorption experiments were conducted using columns packed with cement particles of different sizes. From the analysis of the breakthrough curve, tritium diffusivity in macropores and microparticles were evaluated.(2)From the short-term tritium release experiments, effective desorption rate constants were evaluated and the effects of temperature and moisture were studied.(3)In the long-term tritium release experiments to 6000h, the tritium release mechanism was found to be composed of three kinds of water: initially from capillary water, and in the second stage from gel water and from the water in the cement crystal.(4)Tritium release behavior by heat treatment to 800 C was studied. A high temperature above 600 C was required for the tritium trapped in the crystal water to be released. (orig.)

Interpersonal Circumplex Profiles Of Persistent Depression: Goals, Self-Efficacy, Problems, And Effects Of Group Therapy.

Science.gov (United States)

Locke, Kenneth D; Sayegh, Liliane; Penberthy, J Kim; Weber, Charlotte; Haentjens, Katherine; Turecki, Gustavo

2017-06-01

We assessed severely and persistently depressed patients' interpersonal self-efficacy, problems, and goals, plus changes in interpersonal functioning and depression during 20 weeks of group therapy. Outpatients (32 female, 26 male, mean age = 45 years) completed interpersonal circumplex measures of goals, efficacy, and problems before completing 20 weeks of manualized group therapy, during which we regularly assessed depression and interpersonal style. Compared to normative samples, patients lacked interpersonal agency, including less self-efficacy for expressive/assertive actions; stronger motives to avoid conflict, scorn, and humiliation; and more problems with being too submissive, inhibited, and accommodating. Behavioral Activation and especially Cognitive Behavioral Analysis System of Psychotherapy interventions produced improvements in depression and interpersonal agency, with increases in "agentic and communal" efficacy predicting subsequent decreases in depression. While severely and persistently depressed patients were prone to express maladaptive interpersonal dispositions, over the course of group therapy, they showed increasingly agentic and beneficial patterns of cognitions, motives, and behaviors. © 2016 Wiley Periodicals, Inc.

Controversies in breast cancer: adjuvant and neoadjuvant therapy.

Science.gov (United States)

Montemurro, Filippo; Redana, Stefania; Valabrega, Giorgio; Aglietta, Massimo

2005-06-01

Initial randomised studies of chemotherapy and endocrine therapy showed that systemic treatments had a substantial impact on the survival of women with early breast cancer. The original assumption was that the efficacy of these treatments was limited to those patients presenting with more adverse prognostic features. Subsequently, meta-analyses of randomised trials revealed that the benefits of chemotherapy and endocrine therapy are not mutually exclusive and extend to all the prognostic subgroups. However, the absolute benefit varies according to baseline characteristics such as tumour stage and other biological factors. Over the last 10 years, considerable progress has been made with the introduction of new drugs into the adjuvant and neoadjuvant treatment of women with breast cancer. Taxanes and third-generation aromatase inhibitors are providing proof of additional benefits compared with standard reference treatments. In parallel, research on the biology of breast cancer is establishing novel prognostic and predictive factors, which may allow better treatment tailoring. Currently, however, women with early breast cancer and their doctors face the difficult task of making therapeutic decisions often based on early results from positive studies. In a disease where follow up is crucial to fully assess the benefit and long-term toxicities of an intervention, current knowledge leaves unanswered questions that generate debate and controversy. This review will summarise recent results from randomised trials of adjuvant and neoadjuvant therapy in women with early breast cancer and focus on the current controversies.

Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

Science.gov (United States)

Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

2018-03-14

Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

Music Therapy: A Career in Music Therapy

Science.gov (United States)

About Music Therapy & Music Therapy Training M usic therapy is a healthcare profession that uses music to help individuals of all ages improve physical, cognitive, emotional, and social functioning. Music therapists work with children and adults with developmental ...

Outcome of Subsequent Labour After Primary Caesarean Section ...

African Journals Online (AJOL)

Context: Teenage mothers are at risk of numerous problems among which is cephalopeelvic disproportion or obstructed labour because of small and immature pelvis. This leads to a tendency to allowing trial of scar in subsequent pregnancies because the teenage pelvis might not have reached full capacity as at the time of ...

Firms’ Negative Perceptions on Patents, Technology Management Strategies, and Subsequent Performance

Directory of Open Access Journals (Sweden)

Eun Jin Han

2017-03-01

Full Text Available While patents do have many advantages, their disadvantages include requiring disclosure of technical information and imposing the burden of patenting and litigation costs. In this study, we investigate the relationship between a firm’s negative perception on patents, technology management strategies, and subsequent performance. For this purpose, we use a categorical canonical correlation analysis of the top 200, large, R&D-intensive firms in Korea. We find that negative perceptions such as burdensome transaction costs, non-patenting culture, and uncertainty of the outcome of patent litigation are associated with firms’ technology management strategies, such as purchase of licenses, and subsequent performance, such as an increase in the number of inventions from the cross-fertilization of different technologies. The results of this study are expected to contribute to a better understanding of firms’ negative attitudes toward the effects of patents, their subsequent technology management strategies, and resulting performance.

The perception of the illness with subsequent outcome measure in more favorable in continuos peritoneal dialysis vs hemodialysis in the framework of appraisal model of stress.

Science.gov (United States)

Nowak, Zbigniew; Laudański, Krzysztof

2014-01-01

The aim of the study was to use the appraisal model of stress to compare hemodialysis (HD) and continuous peritoneal dialysis (CAPD) patients with special focus on the perception of end-stage renal disease and subsequent emotional profile and health related quality of life (HQoL) in. We hypothesize that different circumstances related to both modes of therapies will result in dissimilar perception of chronic illness with subsequent changes in emotional profile and heath related quality of life. The total of 88 patients with end stage renal disease (ESRD) enrolled in hemodialysis (n=52; HD) or continuous peritoneal dialysis (n=36; CAPD) were given a battery of psychological tests: The Profile of Mood States, The Nottingham Health Profile, The Stress Situation Assessment Questionnaire, The Social Appreciation Questionnaire and The Situation and Trait and Anxiety Inventory. All patients perceived ESRD in terms of a loss and a threat. Moreover, CAPD patients evaluated ESRD as a challenge. Despite different perception of ESRD no significant difference in the level of fear, anxiety or emotional profile was found. Both HD and CAPD patient were reported more fatigue/inertia and confusion/bewilderment than control groups. The main health related complaints were similar in both ESRD patients with major complaints of sleeping disturbances, motor limitations and lack of energy. From the psychological point of view, CAPD treatment seems more like challenge to the enrolled patient which is positive outcome. Despite different appraisal of stress mood and health related complaints were similar in both groups. This may be a result of optimal regulation of cognitive perception of the stress depending on the circumstances of therapy.

Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy.

Science.gov (United States)

Kamisawa, Terumi; Egawa, Naoto; Inokuma, Shigeko; Tsuruta, Kouji; Okamoto, Atsutake; Kamata, Noriko; Nakamura, Teruo; Matsukawa, Masakatsu

2003-10-01

Autoimmune pancreatitis (AIP) is a distinct clinical entity in which an autoimmune mechanism may be involved in pathogenesis. To investigate salivary gland function in addition to pancreatic endocrine and exocrine function in patients with AIP, and to determine changes occurring after steroid therapy. Fasting serum glucose levels, oral glucose tolerance tests or glycosylated hemoglobin values were examined in 19 patients with AIP. N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test, sialochemistry and parotid gland scintigraphy were performed in 8 patients. Eight patients had evidence of DM. Steroid therapy subsequently improved insulin secretion and glycemic control in 3 of 5 patients treated. Pancreatic exocrine function was reduced in 88% of patients. Impaired pancreatic exocrine function improved after steroid therapy in 3 of 6 patients treated. The 3 patients also showed treatment-related improvement in endocrine function. Concentration of beta2-microglobulin in saliva was significantly raised in patients with AIP compared with controls (P gland dysfunction improved after steroid therapy in all 5 patients treated. Pancreatic endocrine and exocrine and salivary gland function were frequently impaired in patients with AIP, and steroid therapy was occasionally effective for these dysfunctions.

Cardiovascular Risk Following Fertility Therapy: Systematic Review and Meta-Analysis.

Science.gov (United States)

Dayan, Natalie; Filion, Kristian B; Okano, Marisa; Kilmartin, Caitlin; Reinblatt, Shauna; Landry, Tara; Basso, Olga; Udell, Jacob A

2017-09-05

The longer term cardiovascular effects of fertility therapy are unknown. The aim of this study was to summarize data linking fertility therapy with subsequent cardiovascular outcomes. We systematically searched published reports for studies addressing the question "does fertility therapy increase the risk of longer term cardiovascular outcomes?" We included: 1) human studies; 2) case control, cohort, or randomized designs with 3) exposure to fertility therapy and 4) cardiovascular outcomes clearly reported; 5) presence of comparison group; 6) minimum 1-year follow-up; and 7) adjustment for age. Two independent reviewers screened abstracts, titles, and full texts, and assessed study quality. We used the DerSimonian and Laird random-effects models to pool hazard ratios (HRs) with 95% confidence intervals (CIs) of the following outcomes: acute cardiac event; stroke; venous thromboembolism; hypertension; and diabetes mellitus, comparing women who received fertility therapy with those who did not. Six observational studies met inclusion criteria including 41,910 women who received fertility therapy and 1,400,202 women who did not. There was no increased risk of a cardiac event (pooled HR: 0.91; 95% CI: 0.67 to 1.25; I 2  = 36.6%), or diabetes mellitus (pooled HR: 0.93; 95% CI: 0.87 to 1.001; I 2  = 0%). Results were not pooled for hypertension (I 2  = 95.0%) and venous thromboembolism (I 2  = 82.3%). There was a trend toward higher risk of stroke (pooled HR: 1.25; 95% CI: 0.96 to 1.63; I 2  = 0%). The small number of studies and significant heterogeneity precludes definitive reassurance about the longer term cardiovascular safety of these treatments, particularly stroke. Future studies are needed to address ongoing knowledge gaps in this area. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

VAC therapy to promote wound healing after surgical revascularisation for critical lower limb ischaemia.

Science.gov (United States)

De Caridi, Giovanni; Massara, Mafalda; Greco, Michele; Pipitò, Narayana; Spinelli, Francesco; Grande, Raffaele; Butrico, Lucia; de Franciscis, Stefano; Serra, Raffaele

2016-06-01

Vacuum-assisted closure (VAC) therapy is a new emerging non-invasive system in wound care, which speeds up wound healing by causing vacuum, improving tissue perfusion and suctioning the exudates, and facilitating the removal of bacteria from the wound. The application of sub-atmospheric pressure on the lesions seems to alter the cytoskeleton of the cells on the wound bed, triggering a cascade of intracellular signals that increase the rate of cell division and subsequent formation of granulation tissue. The aim of this study is to analyse the results of VAC therapy used as an adjuvant therapy for the treatment of foot wounds in patients affected by critical limb ischaemia (CLI) (Rutherford 6 class) after distal surgical revascularisation, to promote and accelerate the healing of ulcers. Twenty-nine patients (20 males, 9 females; mean age 68·4) affected by CLI of Rutherford 6 class, after surgical revascularisation of the lower limb, underwent VAC therapy in order to speed up wound healing. Complete wound healing was achieved in 19 patients (65·51%), in an average period of 45·4 ± 25·6 days. VAC therapy is a valid aid, after surgical revascularisation, to achieve rapid healing of foot lesions in patients with CLI. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to bedside

International Nuclear Information System (INIS)

Lewin, Jeremy; Rao, Aparna; Mileshkin, Linda; Cullinane, Carleen; Akhurst, Tim; Eu, Peter; Waldeck, Kelly; Watkins, D.N.; Hicks, Rodney J.

2015-01-01

Small cell cancers (SmCC), whether pulmonary (SCLC) or extrapulmonary, have a poor prognosis unless localised at diagnosis. Given a proportion of these cancers express somatostatin receptor subtype 2 (SSTR2), we aimed to investigate the efficacy of targeted peptide receptor chemoradionuclide therapy (PRCRT). In this preclinical study, we used a SCLC xenograft mouse model with high expression of SSTR2 to investigate the effect of peptide receptor radionuclide therapy (PRRT) with chemotherapy compared to either alone. We subsequently explored the clinical utility in a patient with SmCC with high SSTR expression treated with PRCRT. Robust expression of SSTR2 in NCI-H69 SCLC xenografts was documented by 68 Ga-DOTA-octreotate (GaTate) (tumour to background uptake ratio = 35). The combination of PRRT using 177 Lu-DOTA-octreotate (LuTate) with carboplatin/etoposide (C/E) chemotherapy was more effective than either LuTate or C/E alone for regression of the NCI-H69 model (p value < 0.05). PRCRT was associated with significantly prolonged survival versus PRRT (p value = 0.0001) or chemotherapy alone (p value = 0.0058). In the subsequent case study, a patient with relapsed SmCC with high SSTR2 expression on GaTate PET underwent PRCRT with radiosensitising etoposide with evidence of a complete metabolic response for 4 months. Given the limited treatment options in this setting, PRCRT is a promising therapeutic option for SSTR2-expressing SmCC. (orig.)

Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to bedside

Energy Technology Data Exchange (ETDEWEB)

Lewin, Jeremy; Rao, Aparna; Mileshkin, Linda [Division of Hematology and Medical Oncology, East Melbourne, VIC (Australia); Cullinane, Carleen [Division of Cancer Research, East Melbourne, VIC (Australia); The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC (Australia); Akhurst, Tim; Eu, Peter [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Waldeck, Kelly [Division of Cancer Research, East Melbourne, VIC (Australia); Watkins, D.N. [Monash University, Monash Institute of Medical Research, Clayton, VIC (Australia); Hicks, Rodney J. [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC (Australia)

2015-01-15

Small cell cancers (SmCC), whether pulmonary (SCLC) or extrapulmonary, have a poor prognosis unless localised at diagnosis. Given a proportion of these cancers express somatostatin receptor subtype 2 (SSTR2), we aimed to investigate the efficacy of targeted peptide receptor chemoradionuclide therapy (PRCRT). In this preclinical study, we used a SCLC xenograft mouse model with high expression of SSTR2 to investigate the effect of peptide receptor radionuclide therapy (PRRT) with chemotherapy compared to either alone. We subsequently explored the clinical utility in a patient with SmCC with high SSTR expression treated with PRCRT. Robust expression of SSTR2 in NCI-H69 SCLC xenografts was documented by {sup 68}Ga-DOTA-octreotate (GaTate) (tumour to background uptake ratio = 35). The combination of PRRT using {sup 177}Lu-DOTA-octreotate (LuTate) with carboplatin/etoposide (C/E) chemotherapy was more effective than either LuTate or C/E alone for regression of the NCI-H69 model (p value < 0.05). PRCRT was associated with significantly prolonged survival versus PRRT (p value = 0.0001) or chemotherapy alone (p value = 0.0058). In the subsequent case study, a patient with relapsed SmCC with high SSTR2 expression on GaTate PET underwent PRCRT with radiosensitising etoposide with evidence of a complete metabolic response for 4 months. Given the limited treatment options in this setting, PRCRT is a promising therapeutic option for SSTR2-expressing SmCC. (orig.)

KEY COMPARISON: CCQM-K27-Subsequent: Key Comparison (subsequent) for the determination of ethanol in aqueous matrix

Science.gov (United States)

Schantz, Michele M.; Duewer, David L.; Parris, Reenie M.; May, Willie E.; Archer, Marcellé; Mussell, Chris; Carter, David; Konopelko, Leonid A.; Kustikov, Yury A.; Krylov, Anatoli I.; Fatina, Olga V.

2005-01-01

Ethanol is important both forensically ('drunk driving' or driving while under the influence, 'DWI', regulations) and commercially (alcoholic beverages). Blood- and breath-alcohol testing can be imposed on individuals operating private vehicles such as cars, boats, or snowmobiles, or operators of commercial vehicles like trucks, planes, and ships. The various levels of blood alcohol that determine whether these operators are considered legally impaired vary depending on the circumstances and locality. Accurate calibration and validation of instrumentation is critical in areas of forensic testing where quantitative analysis directly affects the outcome of criminal prosecutions, as is the case with the determination of ethanol in blood and breath. Additionally, the accurate assessment of the alcoholic content of beverages is a commercially important commodity. In 2002, the CCQM conducted a Key Comparison (CCQM-K27) for the determination of ethanol in aqueous matrix with nine participants. A report on this project has been approved by the CCQM and can be found at the BIPM website and in this Technical Supplement. CCQM-K27 comprised three samples, one at low mass fraction of ethanol in water (nominal concentration of 0.8 mg/g), one at high level (nominal concentration of 120 mg/g), and one wine matrix (nominal concentration of 81 mg/g). Overall agreement among eight participants using gas chromatography with flame ionization detection (GC-FID), titrimetry, isotope dilution gas chromatography/mass spectrometry (GC-IDMS), and gas chromatography-combustion-isotope ratio mass spectrometry (ID-GC-C-IRMS) was good. The ninth participant used a headspace GC-FID method that had not been validated in an earlier pilot study (CCQM-P35). A follow-on Key Comparison, CCQM-K27-Subsequent, was initiated in 2003 to accommodate laboratories that had not been ready to benchmark their methods in the original CCQM-K27 study or that wished to benchmark a different method. Four levels of

Integrative dynamic therapy for bulimia nervosa: An evidence-based case study.

Science.gov (United States)

Richards, Lauren K; Shingleton, Rebecca M; Goldman, Rachel; Siegel, Deborah; Thompson-Brenner, Heather

2016-06-01

Both cognitive-behavioral therapy (CBT) and psychodynamic psychotherapy are commonly used to treat eating disorders. To further investigate the effectiveness of integrative dynamic therapy (IDT) for bulimia nervosa (BN), our research group undertook a randomized, controlled pilot study comparing IDT with CBT for BN. The case described here was selected from a sample of N = 38 female patients with the symptoms of BN who enrolled in the study. IDT incorporated aspects of the first 4-week stage of CBT, including psychoeducation, self-monitoring, and regular eating. Subsequently, the treatment focused on emotional expression, emotion regulation (defenses), intrapsychic conflict, and interpersonal relationships. The objectives of the report are to demonstrate the effectiveness of an integrative approach to the treatment of eating disorders to address the symptoms of BN and personality issues using pre-, mid-, and posttreatment data, and to illustrate the patient and clinician reactions to each approach to treatment using excerpts from session transcripts and alliance data. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The effects of free recall testing on subsequent source memory.

Science.gov (United States)

Brewer, Gene A; Marsh, Richard L; Meeks, Joseph T; Clark-Foos, Arlo; Hicks, Jason L

2010-05-01

The testing effect is the finding that prior retrieval of information from memory will result in better subsequent memory for that material. One explanation for these effects is that initial free recall testing increases the recollective details for tested information, which then becomes more available during a subsequent test phase. In three experiments we explored this hypothesis using a source-monitoring test phase after the initial free recall tests. We discovered that memory is differentially enhanced for certain recollective details depending on the nature of the free recall task. Thus further research needs to be conducted to specify how different kinds of memorial details are enhanced by free recall testing.

Development of IAEA description of passive safety and subsequent thoughts

Energy Technology Data Exchange (ETDEWEB)

Lang, P M [USDOE, Washington, DC (United States)

1996-12-01

The description of passive components and systems published by the IAEA in its TECDOC-626 was developed in the course of a Technical Committee Meeting held in Sweden and two subsequent Consultants Meetings held in Vienna. This description is reviewed and discussed in terms of the philosophies behind it, alternatives considered, problems encountered, and conclusions drawn. Also discussed is an Appendix to the TECDOC, which illustrates the spectrum of possibilities from passive to active by describing four typical categories of passivity. Subsequent thoughts on passive safety include a discussion of its advantages and disadvantages, concluding with a summary of current views and problems with it. (author). 8 refs.

A Novel Image Encryption Algorithm Based on DNA Subsequence Operation

Directory of Open Access Journals (Sweden)

Qiang Zhang

2012-01-01

Full Text Available We present a novel image encryption algorithm based on DNA subsequence operation. Different from the traditional DNA encryption methods, our algorithm does not use complex biological operation but just uses the idea of DNA subsequence operations (such as elongation operation, truncation operation, deletion operation, etc. combining with the logistic chaotic map to scramble the location and the value of pixel points from the image. The experimental results and security analysis show that the proposed algorithm is easy to be implemented, can get good encryption effect, has a wide secret key's space, strong sensitivity to secret key, and has the abilities of resisting exhaustive attack and statistic attack.

Associations between mental disorders and subsequent onset of hypertension

NARCIS (Netherlands)

Stein, Dan J.; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Bruffaerts, Ronny; de Jonge, Peter; Liu, Zharoui; Caldas-de-Almeida, Jose Miguel; O'Neill, Siobhan; Viana, Maria Carmen; Al-Hamzawi, Ali Obaid; Angermeyer, Mattias C.; Benjet, Corina; de Graaf, Ron; Ferry, Finola; Kovess-Masfety, Viviane; Levinson, Daphna; de Girolamo, Giovanni; Florescu, Silvia; Hu, Chiyi; Kawakami, Norito; Haro, Josep Maria; Piazza, Marina; Posada-Villa, Jose; Wojtyniak, Bogdan J.; Xavier, Miguel; Lim, Carmen C. W.; Kessler, Ronald C.; Scott, Kate M.

2014-01-01

Background: Previous work has suggested significant associations between various psychological symptoms (e. g., depression, anxiety, anger, alcohol abuse) and hypertension. However, the presence and extent of associations between common mental disorders and subsequent adult onset of hypertension

Remission of classic rapid cycling bipolar disorder with levothyroxine augmentation therapy in a male patient having clinical hypothyroidism

Directory of Open Access Journals (Sweden)

Chen PH

2015-02-01

Full Text Available Pao-Huan Chen, Yu-Jui Huang Department of Psychiatry, Taipei Medical University Hospital, Taipei, Taiwan Abstract: The literature suggests that patients with bipolar disorder, particularly females, have greater vulnerability to rapid cycling features. Levothyroxine therapy might be potentially useful to attenuate mood instability in this patient group. In contrast, reports on male patients remain limited and controversial. Herein, we report a 32-year-old male patient who had bipolar 1 disorder for 12 years who developed a breakthrough rapid cycling course and first-onset clinical hypothyroidism at the age of 31 years during lithium therapy. After levothyroxine augmentation therapy was introduced, the patient had remission from the rapid cycling illness course along with normalization of serum levels of free T4 and thyroid stimulating hormone in the subsequent year. This observation suggested that investigation of both levothyroxine pharmacology and thyroid pathology in male patients with rapid cycling bipolar disorder might be of much value. Keywords: mood disorder, therapy, thyroid hormone

Radiation therapy patient education using VERT: combination of technology with human care.

Science.gov (United States)

Jimenez, Yobelli A; Lewis, Sarah J

2018-05-13

The Virtual Environment for Radiotherapy Training (VERT) system is a recently available tool for radiation therapy education. The majority of research regarding VERT-based education is focused on students, with a growing area of research being VERT's role in patient education. Because large differences in educational requirements exist between students and patients, focused resources and subsequent evaluations are necessary to provide solid justification for the unique benefits and challenges posed by VERT in a patient education context. This commentary article examines VERT's role in patient education, with a focus on salient visual features, VERT's ability to address some of the spatial challenges associated with RT patient education and how to combine technology with human care. © 2018 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.

Vascular low-flow malformations in children: current concepts for classification, diagnosis and therapy

International Nuclear Information System (INIS)

Puig, Stefan; Casati, Bettina; Staudenherz, Anton; Paya, Kurosh

2005-01-01

Congenital vascular malformations (CVM) are made of dysplastic vessels with no cellular proliferation. Low- or slow-flow malformations (LFM) consist predominantly of venous and/or lymphatic vessels. Correct terminology is necessary for differentiating vascular malformations from tumours such as haemangiomas, in order to prevent ineffective or even adverse therapy. The role of the radiologist in the management of patients is two-fold: making the diagnosis with the use of ultrasound and magnetic resonance imaging, and performing sclerotherapy, which is the treatment of choice. Prior to sclerotherapy, percutaneous phlebography is necessary to visualize the dynamic situation inside the lesion and the flow into the adjacent vascular system. The double-needle technique is a useful therapy option reducing the risk of embolisation of the sclerosing agent. Large lesions might need subsequent surgical treatment. A multidisciplinary approach is substantial for optimal patient management

The Process of Seeking Psychotherapy and Its Impact on Therapy Expectations and Experiences.

Science.gov (United States)

Elliott, Katherine P; Westmacott, Robin; Hunsley, John; Rumstein-McKean, Orly; Best, Marlene

2015-01-01

Seeking psychotherapy can be conceptualized as having three stages: deciding that therapy might help, deciding to seek therapy and contacting a therapist. The present study examined the duration and difficulty of clients' decisions to seek psychotherapy and whether these experiences were predictive of expected difficulty and commitment to the therapy process. One-hundred and fifty-five adults seeking individual psychological services from a university training clinic were assessed before intake; 107 of these participants also completed measures between the third and fourth therapy sessions and at post-therapy. Deciding that therapy might help was reported to be the most difficult step and took the longest, with each subsequent step becoming easier and briefer. At each step, the more difficult the decision, the more time participants took to make it. Higher distress was associated with more difficulty in deciding that therapy might help and deciding to seek therapy. Duration and difficulty of decisions to seek therapy were positively correlated with expectations of difficulty in therapy as measured prior to treatment and following the third session but were not associated with participants' commitment to therapy. The implications of these results for clinicians and mental health services are discussed. The most difficult and time-consuming step for those who seek mental health services is recognizing that their distressing experiences are connected to mental health; clinicians may aid this challenge by providing information on the nature of mental disorders and common symptoms of emotional distress on websites or through other means (e.g., physicians' waiting rooms and advertising campaigns). The next most difficult and time-consuming step for those who seek mental health services is deciding that psychotherapy may help; by providing easily accessible information (e.g., on websites) about what psychotherapy entails, including clinicians' expectations of clients and

Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy

International Nuclear Information System (INIS)

Tirkey, Bulbul; Bhushan, Bharat; Uday Kumar, S.; Gopinath, P.

2017-01-01

Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication. - Highlights: • In this work, BSA-5-FC NPs has been prepared to achieve its sustained release and also facilitate its uptake by cells. • A protein based system has been realized for the first time to deliver prodrug for cancer therapy. • Physico-chemical characterizations further validate the formation of spherical, monodispersed and stable nanoparticles. • The therapeutic efficacy of BSA-5-FC NPs has been validated against CD::UPRT expressing stable cells.

Prodrug encapsulated albumin nanoparticles as an alternative approach to manifest anti-proliferative effects of suicide gene therapy

Energy Technology Data Exchange (ETDEWEB)

Tirkey, Bulbul [Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Bhushan, Bharat; Uday Kumar, S. [Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Gopinath, P., E-mail: pgopifnt@iitr.ernet.in [Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India); Nanobiotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667 (India)

2017-04-01

Conventional anticancer agents are associated with limited therapeutic efficacy and substantial nonspecific cytotoxicity. Thus, there is an imminent need for an alternative approach that can specifically annihilate the cancer cells with minimal side effects. Among such alternative approaches, CD::UPRT (cytosine deaminase uracil phosphoribosyl transferase) suicide gene therapy has tremendous potential due to its high efficacy. Prodrug 5-Fluorocytosine (5-FC) used in combination with CD::UPRT suicide gene suffers from limited solubility which subsequently leads to decline in therapeutic efficacy. In order to overcome this, 5-FC encapsulated bovine serum albumin nanoparticles (BSA-5-FC NPs) were prepared in this work by desolvation method. Physico-chemical characterizations studies revealed amorphous nature of BSA-5-FC NPs with uniform spherical morphology. Apart from increase in solubility, encapsulated 5-FC followed slow and sustained release profile. Suicide gene expressing stable clone of L-132 cells were adapted for investigating therapeutic potential of BSA-5-FC NPs. These nanoparticles were readily taken up by the cells in a concentration dependent manner and subsequently manifested apoptosis, which was further confirmed by morphological examination and gene expression analysis. These findings clearly illustrate that CD::UPRT suicide gene therapy can be efficiently utilized in combination with this nanosystem for improved suicide gene therapy and tumor eradication. - Highlights: • In this work, BSA-5-FC NPs has been prepared to achieve its sustained release and also facilitate its uptake by cells. • A protein based system has been realized for the first time to deliver prodrug for cancer therapy. • Physico-chemical characterizations further validate the formation of spherical, monodispersed and stable nanoparticles. • The therapeutic efficacy of BSA-5-FC NPs has been validated against CD::UPRT expressing stable cells.

Feedback on Facebook Fails to Predict the User’s Subsequent Posting

Directory of Open Access Journals (Sweden)

Sherwin E. Balbuena

2017-11-01

Full Text Available Facebook use is a new and complex social behavior that has stimulated research interests in psychology. Due to a distinct lack of theoretical basis for this new communication phenomenon, a number of studies established the significant association between personality traits and Facebook use. This study investigated the motivational effect of friends’ feedback on the user’s subsequent Facebook posting and examined the correspondence between the user’s perceived motivation and actual motivation-behavior outcome using a new method. Results showed no significant association between the number of feedback and the number of subsequent posts, users’ perceived motivations were consistent with their actual motivation-behavior outcomes, users’ self-reports validated the new results and confirmed the previous findings that Facebook use is aimed at satisfying the individual’s needs for belongingness, self-presentation, and social information-seeking. It is suggested that the amount of feedback on Facebook is an ineffective determinant of the users’ frequency of subsequent postings.

Does the presence of priming hinder subsequent recognition or recall performance?

Science.gov (United States)

Stark, Shauna M; Gordon, Barry; Stark, Craig E L

2008-02-01

Declarative and non-declarative memories are thought be supported by two distinct memory systems that are often posited not to interact. However, Wagner, Maril, and Schacter (2000a) reported that at the time priming was assessed, greater behavioural and neural priming was associated with lower levels of subsequent recognition memory, demonstrating an interaction between declarative and non-declarative memory. We examined this finding using a similar paradigm, in which participants made the same or different semantic word judgements following a short or long lag and subsequent memory test. We found a similar overall pattern of results, with greater behavioural priming associated with a decrease in recognition and recall performance. However, neither various within-participant nor various between-participant analyses revealed significant correlations between priming and subsequent memory performance. These data suggest that both lag and task have effects on priming and declarative memory performance, but that they are largely independent and occur in parallel.

Laser Induced Selective Activation For Subsequent Autocatalytic Electroless Plating

DEFF Research Database (Denmark)

Zhang, Yang

. The third hypothesis is that the activation and rinsing process can be described by diffusion. This hypothesis is proved using Fick’s diffusion laws combined with the short-time-plating experiment. The influence of laser parameters on the surface structure is investigated for Nd:YAG, UV, and fiber lasers......The subject of this PhD thesis is “Laser induced selective activation for subsequent autocatalytic electroless plating.” The objective of the project is to investigate the process chains for micro structuring of polymer surfaces for selective micro metallization. Laser induced selective activation...... (LISA) is introduced and studied as a new technique for producing 3D moulded interconnect devices (3D-MIDs). This technique enables the metallization of polymer surface modified by laser and subsequently activated by a PdCl2/SnCl2 system. Various technologies exist on an industrial level...

Modeling ADHD-type arousal with unilateral frontal cortex damage in rats and beneficial effects of play therapy.

Science.gov (United States)

Panksepp, Jaak; Burgdorf, Jeff; Turner, Cortney; Gordon, Nakia

2003-06-01

It has been recently shown that human adolescents with Attention Deficit/Hyperactivity Disorder (ADHD) have frontal lobe deficits, especially on the right sides of their brains (). ADHD is commonly treated with psychostimulants which may have adverse consequences. Hence, less invasive therapies need to be developed. In the present work, we tested the ability of right frontal lesions to induce hyperactivity in rats. We also evaluated the effects of chronic play therapy during early adolescence to reduce both hyperactivity and the elevated playfulness later in development. Play therapy was able to reduce both hyperactivity and excessive playfulness. In additional work, we found that access to rough-and-tumble play in normal animals could enhance subsequent behavioral indices of behavioral inhibition (i.e., freezing in response to a startle stimulus) that appeared to be independent of increased fearfulness and fatigue. Overall, these results suggest that (1) neonatal frontal lobe lesions can be used as an animal model of the overactivity in ADHD and (2) rough-and-tumble play therapy may be a new useful treatment for ADHD.

Two-step polymer- and liposome-enzyme prodrug therapies for cancer: PDEPT and PELT concepts and future perspectives.

Science.gov (United States)

Scomparin, Anna; Florindo, Helena F; Tiram, Galia; Ferguson, Elaine L; Satchi-Fainaro, Ronit

2017-09-01

Polymer-directed enzyme prodrug therapy (PDEPT) and polymer enzyme liposome therapy (PELT) are two-step therapies developed to provide anticancer drugs site-selective intratumoral accumulation and release. Nanomedicines, such as polymer-drug conjugates and liposomal drugs, accumulate in the tumor site due to extravasation-dependent mechanism (enhanced permeability and retention - EPR - effect), and further need to cross the cellular membrane and release their payload in the intracellular compartment. The subsequent administration of a polymer-enzyme conjugate able to accumulate in the tumor tissue and to trigger the extracellular release of the active drug showed promising preclinical results. The development of polymer-enzyme, polymer-drug conjugates and liposomal drugs had undergone a vast advancement over the past decades. Several examples of enzyme mimics for in vivo therapy can be found in the literature. Moreover, polymer therapeutics often present an enzyme-sensitive mechanism of drug release. These nanomedicines can thus be optimal substrates for PDEPT and this review aims to provide new insights and stimuli toward the future perspectives of this promising combination. Copyright © 2017 Elsevier B.V. All rights reserved.

Vinorelbine as first-line or second-line therapy for advanced breast cancer

DEFF Research Database (Denmark)

Langkjer, Sven T; Ejlertsen, Bent; Mouridsen, Henning

2008-01-01

INTRODUCTION: This study was conducted to establish the maximum tolerated dose (MTD) of intravenous vinorelbine and on the determined dose to assess efficacy and safety in patients with metastatic breast cancer previously treated with epirubicin. PATIENTS AND METHODS: Patients had histologically...... proven breast cancer and had received a prior epirubicin based regimen either adjuvant or as first line therapy for advanced disease. Vinorelbine was administered intravenously day 1 and 8 in a 3 weeks' schedule. Subsequently 48 additional patients were treated at one dose-level below MTD. RESULTS: Fifty...

How phenobarbital revolutionized epilepsy therapy: the story of phenobarbital therapy in epilepsy in the last 100 years.

Science.gov (United States)

Yasiry, Zeid; Shorvon, Simon D

2012-12-01

Phenobarbital (phenobarbitone) was first used as an antiepileptic drug 100 years ago, in 1912. This article tells the story of the discovery of its antiepileptic action, its early development, and the subsequent course of its clinical use over the 100-year period. The side effects, pharmacokinetics, and misuse of barbiturates are considered, along with the more recent clinical trials and the drug's current clinical utilization. The introduction of controlled drug regulations, the comparative cost of phenobarbital, and its inclusion on the World Health Organization (WHO) essential drug list are discussed. It is one of the few drugs on the formulary in 1912 that is still listed today, and remarkably its efficacy in epilepsy has not been significantly bettered. The current recommendation by the WHO is that phenobarbital should be offered as the first option for therapy for convulsive epilepsy in adults and children if availability can be ensured. This is rated as a strong recommendation because of the proven efficacy and low cost of phenobarbital, and despite its perceived side-effect profile and the practical problems of access. Whether this recommendation puts "a hierarchy on the brain," as has been suggested, is arguable. Much still needs to be learned about the drug's effects, and the issues raised by phenobarbital have lessons for all antiepileptic drug therapy. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Delays in initiation of acyclovir therapy in herpes simplex encephalitis.

Science.gov (United States)

Hughes, Peter S; Jackson, Alan C

2012-09-01

Diagnosis of herpes simplex encephalitis (HSE) is based on clinical findings, MRI, and detection of herpes simplex virus (HSV) DNA in cerebrospinal fluid (CSF) using polymerase chain reaction amplification. Delays in starting treatment are associated with poorer clinical outcomes. We assessed the timing of initiation of acyclovir therapy in HSE. Inpatient databases from seven hospitals in Winnipeg, Manitoba were used to identify individuals diagnosed with encephalitis and HSE from 2004 to 2009. The time taken to initiate therapy with acyclovir and the reasons for delays were determined. Seventy-seven patients were identified; 69 (90%) received acyclovir; in the others a non-HSV infection was strongly suspected. Thirteen patients were subsequently confirmed to have HSE. Acyclovir was initiated a median of 21 hours (3-407) after presentation in encephalitis cases, and a median of 11 hours (3-118) in HSE. The most common reason for delay was a failure to consider HSE in the differential diagnosis, despite suggestive clinical features. Where therapy was delayed in HSE patients, the decision to begin acyclovir was prompted by transfer of the patient to a different service (55%), recommendations by consultants (18%), imaging results (18%), and CSF pleocytosis (9%). Delays in initiating acyclovir for HSE are common, and are most often due to a failure to consider HSE in a timely fashion on presentation. In order to improve patient outcomes, physicians should be more vigilant for HSE, and begin acyclovir therapy expeditiously on the basis of clinical suspicion rather than waiting for confirmatory tests.

Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review.

LENUS (Irish Health Repository)

Behan, L A

2012-02-01

Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.

Secondary resistance to cabergoline therapy in a macroprolactinoma: a case report and literature review.

LENUS (Irish Health Repository)

Behan, L A

2009-02-04

Primary resistance to dopamine agonists occurs in 10-15% of prolactinomas but secondary resistance following initial biochemical and anti-proliferative response is very rare and has only been hitherto described in four previous cases, two with bromocriptine and two with cabergoline. We describe a case of a 57-year-old woman who presented with a large macroprolactinoma with suprasellar extension. She was initially treated with bromocriptine therapy with a resolution of symptoms, marked reduction in prolactin concentration and complete tumour shrinkage; a response which was subsequently maintained on cabergoline. After 8 years of dopamine agonist therapy, her prolactin concentration began to rise and there was symptomatic recurrence of her tumour despite escalating doses of cabergoline up to 6 mg weekly. Non-compliance was outruled by observed inpatient drug administration. The patient underwent surgical debulking followed by radiotherapy with good response. This case adds to the previous two cases of secondary resistance to cabergoline therapy in prolactinomas a marked initial response. While the mechanism of secondary resistance remains unknown and not possible to predict, close observation of prolactinoma patients on treatment is necessary.

Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery.

Science.gov (United States)

Petrella, Francesco; Rimoldi, Isabella; Rizzo, Stefania; Spaggiari, Lorenzo

2017-11-23

Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

Effectiveness of Electroconvulsive Therapy for Depression and Cotard’s Syndrome in a Patient with Frontotemporal Lobe Dementia

Directory of Open Access Journals (Sweden)

Toshiyuki Kobayashi

2012-01-01

Full Text Available In the field of psychogeriatrics, the differential diagnosis of depression and dementia, as well as the treatment of depression and comorbid dementia, is an important issue. In this paper, the authors present the case of a 72-year-old woman with Cotard’s syndrome and frontotemporal dementia (FTD who was admitted to a psychiatric hospital with delusions of negation accompanied by depressive symptoms. Pharmacotherapy over a 2-year hospitalization was unsuccessful, and she was subsequently transferred to our university hospital. A total of 18 sessions of electroconvulsive therapy released her from psychomotor inhibition, appetite loss, and Cotard’s delusions. The indication for electroconvulsive therapy in patients with dementia is discussed.

Satisfaction in motion: Subsequent search misses are more likely in moving search displays.

Science.gov (United States)

Stothart, Cary; Clement, Andrew; Brockmole, James R

2018-02-01

People often conduct visual searches in which multiple targets are possible (e.g., medical X-rays can contain multiple abnormalities). In this type of search, observers are more likely to miss a second target after having found a first one (a subsequent search miss). Recent evidence has suggested that this effect may be due to a depletion of cognitive resources from tracking the identities and locations of found targets. Given that tracking moving objects is resource-demanding, would finding a moving target further increase the chances of missing a subsequent one? To address this question, we had participants search for one or more targets hidden among distractors. Subsequent search misses were more likely when the targets and distractors moved throughout the display than when they remained stationary. However, when the found targets were highlighted in a unique color, subsequent search misses were no more likely in moving displays. Together, these results suggest that the effect of movement is likely due to the increased cognitive demands of tracking moving targets. Overall, our findings reveal that activities that involve searching for moving targets (e.g., driving) are more susceptible to subsequent search misses than are those that involve searching for stationary targets (e.g., baggage screening).

Accelerating cancer therapy development: the importance of combination strategies and collaboration. Summary of an Institute of Medicine workshop.

Science.gov (United States)

LoRusso, Patricia M; Canetta, Renzo; Wagner, John A; Balogh, Erin P; Nass, Sharyl J; Boerner, Scott A; Hohneker, John

2012-11-15

Cancer cells contain multiple genetic changes in cell signaling pathways that drive abnormal cell survival, proliferation, invasion, and metastasis. Unfortunately, patients treated with single agents inhibiting only one of these pathways--even if showing an initial response--often develop resistance with subsequent relapse or progression of their cancer, typically via the activation of an alternative uninhibited pathway. Combination therapies offer the potential for inhibiting multiple targets and pathways simultaneously to more effectively kill cancer cells and prevent or delay the emergence of drug resistance. However, there are many unique challenges to developing combination therapies, including devising and applying appropriate preclinical tests and clinical trial designs, prioritizing which combination therapies to test, avoiding overlapping toxicity of multiple agents, and overcoming legal, cultural, and regulatory barriers that impede collaboration among multiple companies, organizations, and/or institutions. More effective strategies to efficiently develop combination cancer therapies are urgently needed. Thus, the Institute of Medicine's National Cancer Policy Forum recently convened a workshop with the goal of identifying barriers that may be impeding the development of combination investigational cancer therapies, as well as potential solutions to overcome those barriers, improve collaboration, and ultimately accelerate the development of promising combinations of investigational cancer therapies. ©2012 AACR.

Preventive therapy for latent tuberculosis infection—the promise and the challenges

Directory of Open Access Journals (Sweden)

G.J. Fox

2017-03-01

Full Text Available Around one third of the world's population may harbour latent tuberculosis infection (LTBI, an asymptomatic immunological state that confers a heightened risk of subsequently developing tuberculosis (TB. Effectively treating LTBI will be essential if the End TB Strategy is to be realized. This review evaluates the evidence in relation to the effectiveness of preventive antibiotic therapy to treat LTBI due to both drug-susceptible and drug-resistant bacteria. Current national and international preventive therapy guidelines are summarized, as well as ongoing randomized trials evaluating regimens to prevent drug-resistant TB. Populations that may benefit most from screening and treatment for LTBI include close contacts of patients with TB (particularly children under 5 years of age and individuals with substantial immunological impairment. The risks and benefits of treatment must be carefully balanced for each individual. Electronic decision support tools offer one way in which clinicians can help patients to make informed decisions. Modelling studies indicate that the expanded use of preventive therapy will be essential to achieving substantial reductions in the global TB burden. However, the widespread scale-up of screening and treatment will require careful consideration of cost-effectiveness, while ensuring the drivers of ongoing disease transmission are also addressed.

Radiation therapy of Kaposi's sarcoma in AIDS: Memorial Sloan-Kettering experience

International Nuclear Information System (INIS)

Nisce, L.Z.; Safai, B.

1985-01-01

In 1980 the authors reported their experience in the management of Kaposi's sarcoma (KS) affecting elderly men of Jewish or Italian descent. Since the outbreak of KS in 1981 among young male homosexuals with acquired immune deficiency syndrome (AIDS) the KS in the elderly has been subsequently called classical Kaposi's sarcome (CKS) in order to differentiate it from the KS in AIDS. The radiosensitivity of CKS is well documented. This report describes the authors' early experience in the radiation therapy of KS in AIDS compared with CKS and also discusses the problems related to the irradiation of the immunocompromised patient

25 years of tinnitus retraining therapy.

Science.gov (United States)

Jastreboff, P J

2015-04-01

This year marks 25 years of tinnitus retraining therapy (TRT), the approach that aims to eliminate tinnitus as a problem by extinguishing functional connections between the auditory and the limbic and autonomic nervous systems to achieve habituation of tinnitus-evoked reactions and subsequently habituation of perception. TRT addresses directly decreased sound tolerance (DST) as well as tinnitus. TRT consists of counseling and sound therapy, both based on the neurophysiological model of tinnitus. The main goal of retraining counseling is to reclassify tinnitus into the category of a neutral stimulus, while the main goal of sound therapy is to decrease the strength of tinnitus-related neuronal activity. A unique aspect of TRT is that because treatment is aimed to work above the tinnitus source, and at connections linking the auditory and other systems in the brain, the etiology of tinnitus is irrelevant. Any type of tinnitus, as well as somatosounds, can be successfully treated by TRT. Over 100 publications can be found on Medline when using "tinnitus retraining therapy" as a search term. The majority of these publications indicate TRT offers significant help for about 80 % of patients. A randomized clinical trial showing the effectiveness of TRT has been published and another large study is in progress. The principles of the neurophysiological model of tinnitus, and consequently TRT, have not changed in over 25 years of use, but a number of changes have been introduced in TRT implementation. These changes include the recognition of the importance of conditioned reflexes and the dominant role of the subconscious pathways; the introduction of the concept of misophonia (i.e., negative reactions to specific patterns of sound) and the implementation of specific protocols for its treatment; greater emphasis on the concurrent treatment of tinnitus, hyperacusis, misophonia, and hearing loss; extensive modification of counseling; and refinements in sound therapy. The

A Phase II study of palonosetron, aprepitant, dexamethasone and olanzapine for the prevention of cisplatin-based chemotherapy-induced nausea and vomiting in patients with thoracic malignancy.

Science.gov (United States)

Nakashima, Kazuhisa; Murakami, Haruyasu; Yokoyama, Kouichi; Omori, Shota; Wakuda, Kazushige; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Nishiyama, Fumie; Kikugawa, Mami; Kaneko, Masayo; Iwamoto, Yumiko; Koizumi, Satomi; Mori, Keita; Isobe, Takeshi; Takahashi, Toshiaki

2017-09-01

The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy). Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Medical abortion and the risk of subsequent adverse pregnancy outcomes

DEFF Research Database (Denmark)

Virk, Jasveer; Zhang, Jun; Olsen, Jørn

2007-01-01

BACKGROUND: The long-term safety of surgical abortion in the first trimester is well established. Despite the increasing use of medical abortion (abortion by means of medication), limited information is available regarding the effects of this procedure on subsequent pregnancies. METHODS: We...... identified all women living in Denmark who had undergone an abortion for nonmedical reasons between 1999 and 2004 and obtained information regarding subsequent pregnancies from national registries. Risks of ectopic pregnancy, spontaneous abortion, preterm birth (at ... weight (abortion were compared with risks in women who had had a first-trimester surgical abortion. RESULTS: Among 11,814 pregnancies in women who had had a previous first-trimester medical abortion (2710 women...

RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy.

Science.gov (United States)

Pritzker, Kenneth; Pritzker, Laura; Generali, Daniele; Bottini, Alberto; Cappelletti, Maria Rosa; Guo, Baoqing; Parissenti, Amadeo; Trudeau, Maureen

2015-05-01

As there is now evidence that switching clinical nonresponders early in primary systemic therapy to alternate treatment regimens can enhance survival in some breast cancer patients, the need for a robust intermediate endpoint that can guide treatment response across all tumor subtypes is urgent. Recently, chemotherapy drugs have been shown to induce a decrease in RNA quality in tumor cells from breast cancer biopsies in some patients at midtherapy, and that this has been associated with subsequent achievement of pathological complete response (pCR). The decrease in RNA quality has been shown to be associated with RNA disruption; aberrant RNA bands visualized by RNA electrophoresis have been associated with subsequent tumor cell death. The objectives of these studies are to show that a new assay based on induction of RNA disruption in tumor cells by chemotherapy can stratify at midtherapy, pCR responders from non-pCR responders irrespective of clinical response and to present early evidence that clinically useful RNA disruption can be detected as early as 14 days after initiation of treatment. RNA disruption in tumor cells was quantified by analysis of the RNA electrophoresis banding pattern and expressed as an RNA disruption index (RDI). To develop the RNA disruption assay (RDA), RDI was correlated with clinical outcome (pCR) from the NCIC-CTG MA.22 breast cancer clinical trial (ClinicalTrials.gov NCT00066443). RDA Zones were established by stratifying patients using RDI values into Zone 1, Zone 2, and Zone 3. Zone 3 included seven out of eight pCR responders, whereas Zone 1 contained no pCR responders. An intermediate zone (Zone 2) was established which contained one pCR. Subsequently, to determine early drug response, RNA disruption was examined by RDI after 14 days exposure to trastuzumab, zoledronic acid, or letrozole + cyclophosphamide ± sorafenib therapy. In MA.22, RDA stratified 23 of 85 patients in Zone 1 as pCR nonresponders, 24 patients in Zone 2, an

Selective bladder preservation by combined modality therapy for invasive bladder cancer

Energy Technology Data Exchange (ETDEWEB)

Kachnic, L A; Kaufman, D S; Zietman, A L; Dallow, K C; Griffin, P P; Heney, N M; Althausen, A F; Shipley, W U

1995-07-01

Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

Selective bladder preservation by combined modality therapy for invasive bladder cancer

International Nuclear Information System (INIS)

Kachnic, L. A.; Kaufman, D. S.; Zietman, A. L.; Dallow, K. C.; Griffin, P. P.; Heney, N. M.; Althausen, A. F.; Shipley, W. U.

1995-01-01

Purpose/Objective: To assess the success of selective organ preservation or radical cystectomy in a large group of patients with muscle-invasive bladder cancer treated with induction by combined transurethral resection (TURBT), systemic chemotherapy and radiation therapy. Materials and Methods: 106 patients (median age 68 years) were treated with induction by maximal TURBT and 2 cycles of chemotherapy (methotrexate, cisplatin, vinblastine - MCV) followed by 39.6 Gy irradiation in 1.8 Gy fractions with concomitant cisplatin. Tumor response was then evaluated by cystoscopy, rebiopsy, and urine cytology. Complete responders were consolidated with radiation to 64.8 Gy and further cisplatin. Any subsequent isolated invasive local relapse was managed by cystectomy. Patients with any less than a complete response (CR) were recommended cystectomy. Median follow-up was 4.4 years. Kaplan-Meier analysis was used to assess outcome. Results: 74 CR patients (70%) and 7 non-cystectomy candidates with less than a CR (7%) received consolidation chemotherapy and radiation. 13 incomplete responders (12%) underwent immediate cystectomy. 6 patients underwent cystectomy because they could not tolerate induction chemo-radiation. 1 complete response patient underwent radical cystectomy. 83 patients completed their planned therapy but 5 died of treatment related toxicity during induction chemotherapy. Five year actuarial overall survival and disease-specific survival were 52% and 60% respectively. For T2 patients, actuarial overall survival was 63%, and for T3-4, 45%. Five year survival with an intact functioning bladder was 43%. Five year freedom from distant metastases was 66%. Of those who had a CR after TURBT and MCV, the risk of a subsequent invasive bladder relapse was 18% at 5 years. Of those who had a CR after the completion of induction chemotherapy and 39.6 Gy, this risk was 21%. 18 patients (17%) have experienced a non-invasive bladder relapse requiring further TUR and

Working memory overload: fronto-limbic interactions and effects on subsequent working memory function.

Science.gov (United States)

Yun, Richard J; Krystal, John H; Mathalon, Daniel H

2010-03-01

The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction.

Incidence of pelvic organ prolapse repair subsequent to hysterectomy

DEFF Research Database (Denmark)

Lykke, Rune; Blaakær, Jan; Ottesen, Bent

2017-01-01

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the incidence of subsequent pelvic organ prolapse (POP) repair in women following radical hysterectomy versus total abdominal hysterectomy. METHODS: From the Danish National Patient Registry, we collected data on all radical...

Global brain dynamics during social exclusion predict subsequent behavioral conformity.

Science.gov (United States)

Wasylyshyn, Nick; Hemenway Falk, Brett; Garcia, Javier O; Cascio, Christopher N; O'Donnell, Matthew Brook; Bingham, C Raymond; Simons-Morton, Bruce; Vettel, Jean M; Falk, Emily B

2018-02-01

Individuals react differently to social experiences; for example, people who are more sensitive to negative social experiences, such as being excluded, may be more likely to adapt their behavior to fit in with others. We examined whether functional brain connectivity during social exclusion in the fMRI scanner can be used to predict subsequent conformity to peer norms. Adolescent males (n = 57) completed a two-part study on teen driving risk: a social exclusion task (Cyberball) during an fMRI session and a subsequent driving simulator session in which they drove alone and in the presence of a peer who expressed risk-averse or risk-accepting driving norms. We computed the difference in functional connectivity between social exclusion and social inclusion from each node in the brain to nodes in two brain networks, one previously associated with mentalizing (medial prefrontal cortex, temporoparietal junction, precuneus, temporal poles) and another with social pain (dorsal anterior cingulate cortex, anterior insula). Using predictive modeling, this measure of global connectivity during exclusion predicted the extent of conformity to peer pressure during driving in the subsequent experimental session. These findings extend our understanding of how global neural dynamics guide social behavior, revealing functional network activity that captures individual differences.

DNA-synthesis of lymphocytes in hyperthyroid and enthyroid subjects. Effect of 131I therapy on hyperthyroidism

International Nuclear Information System (INIS)

Lundell, G.; Wasserman, J.; Einhorn, N.; Granberg, P.-O.

1976-01-01

The DNA-synthesis of human lymphoid cells as estimated by the measurement of thymidine incorporation in vitro was investigated in healthy controls and in patients with various thyroid disorders before and after therapy. Hyperthyroid patients treated with 131 I and surgery (euthyroid at initial blood sampling before surgery), patients with atoxic nodular goitre treated by surgery and healthy untreated control individuals comprised the material. The synthesis of DNA in lymphocytes was higher in hyperthyroid patients in comparison with euthyroid individuals, and decreased subsequent to 131 I therapy in the hyperthyroid patients. No decrease was recorded in the other groups of patients. No evidence suggesting a change in the lymphocyte reactivity to thyroglobulin was found in any of the patient groups. (author)

Recurrence risk of preterm birth in subsequent twin pregnancy after preterm singleton delivery

NARCIS (Netherlands)

Schaaf, J. M.; Hof, M. H. P.; Mol, B. W. J.; Abu-Hanna, A.; Ravelli, A. C. J.

2012-01-01

Please cite this paper as: Schaaf J, Hof M, Mol B, Abu-Hanna A, Ravelli A. Recurrence risk of preterm birth in subsequent twin pregnancy after preterm singleton delivery.BJOG 2012;119:16241629. Objective To determine the risk of preterm birth in a subsequent twin pregnancy after previous singleton

Oro-cecal transit time : influence of a subsequent meal

NARCIS (Netherlands)

Priebe, MG; Wachters-Hagedoorn, RE; Stellaard, F; Heiner, AM; Elzinga, H; Vonk, RJ

Background Small intestinal and oro-cecal transit time (OCTT) is determined for clinical diagnostics and research purposes. Experimental protocols used vary with respect to the inclusion of a subsequent meal during the test period. This study was conducted to elucidate whether the ingestion of a

Increasing Age and Treatment Modality Are Predictors for Subsequent Diagnosis of Bladder Cancer Following Prostate Cancer Diagnosis

International Nuclear Information System (INIS)

Singh, Anurag K.; Mashtare, Terry L.; McCloskey, Susan A.; Seixas-Mikelus, Stefanie A.; Kim, Hyung L.; May, Kilian Salerno

2010-01-01

Purpose: To determine the effect of prostate cancer therapy (surgery or external beam irradiation, or both or none) on the actuarial incidence of subsequent bladder cancer. Methods and Materials: The Surveillance, Epidemiology, and End Results registry from 1973 to 2005 was analyzed. Treatment was stratified as radiotherapy, surgery, both surgery and adjuvant radiation, and neither modality. Brachytherapy was excluded. Results: In all, 555,337 prostate carcinoma patients were identified; 124,141 patients were irradiated; 235,341 patients were treated surgically; 32,744 patients had both surgery and radiation; and 163,111 patients received neither modality. Bladder cancers were diagnosed in: 1,836 (1.48%) men who were irradiated (mean age, 69.4 years), 2,753 (1.09%) men who were treated surgically (mean age, 66.9 years); 683 (2.09%) men who received both modalities (mean age, 67.4 years), and 1,603 (0.98%) men who were treated with neither modality (mean age, 71.8 years). In each treatment cohort, Kaplan-Meier analyses showed that increasing age (by decade) was a significant predictor of developing bladder cancer (p < 0.0001). Incidence of bladder cancer was significantly different for either radiation or surgery alone versus no treatment, radiation versus surgery alone, and both surgery and radiation versus either modality alone (p < 0.0001). On multivariate analysis, age and irradiation were highly significant predictors of being diagnosed with bladder cancer. Conclusions: Following prostate cancer, increasing age and irradiation were highly significant predictors of being diagnosed with bladder cancer. While use of radiation increased the risk of bladder cancer compared to surgery alone or no treatment, the overall incidence of subsequent bladder cancer remained low. Routine bladder cancer surveillance is not warranted.

Recent Advancements in Gene Therapy for Hereditary Retinal Dystrophies

Directory of Open Access Journals (Sweden)

Ayşe Öner

2017-12-01

Full Text Available Hereditary retinal dystrophies (HRDs are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision, and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles, with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family, highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been proposed as potentially efficacious therapies. Because of its favorable anatomical and immunological characteristics, the eye has been at the forefront of translational gene therapy. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Dozens of promising proofs of concept have been obtained in animal models of HRDs and some of them have been relayed to the clinic. The results from the first clinical trials for a congenital form of blindness have generated great interest and have demonstrated the safety and efficacy of intraocular administrations of viral vectors in humans. This review summarizes the clinical development of retinal gene therapy.

Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma.

Directory of Open Access Journals (Sweden)

Linda Olsson

Full Text Available Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events.

Clonal evolution through loss of chromosomes and subsequent polyploidization in chondrosarcoma.

Science.gov (United States)

Olsson, Linda; Paulsson, Kajsa; Bovée, Judith V M G; Nord, Karolin H

2011-01-01

Near-haploid chromosome numbers have been found in less than 1% of cytogenetically reported tumors, but seem to be more common in certain neoplasms including the malignant cartilage-producing tumor chondrosarcoma. By a literature survey of published karyotypes from chondrosarcomas we could confirm that loss of chromosomes resulting in hyperhaploid-hypodiploid cells is common and that these cells may polyploidize. Sixteen chondrosarcomas were investigated by single nucleotide polymorphism (SNP) array and the majority displayed SNP patterns indicative of a hyperhaploid-hypodiploid origin, with or without subsequent polyploidization. Except for chromosomes 5, 7, 19, 20 and 21, autosomal loss of heterozygosity was commonly found, resulting from chromosome loss and subsequent duplication of monosomic chromosomes giving rise to uniparental disomy. Additional gains, losses and rearrangements of genetic material, and even repeated rounds of polyploidization, may affect chondrosarcoma cells resulting in highly complex karyotypes. Loss of chromosomes and subsequent polyploidization was not restricted to a particular chondrosarcoma subtype and, although commonly found in chondrosarcoma, binucleated cells did not seem to be involved in these events.

Effect of dry period length on milk production in subsequent lactation

DEFF Research Database (Denmark)

Sørensen, J.T.; Enevoldsen, Carsten

1991-01-01

, two treatments were compared within herd. Compared with a 7-wk planned dry period, a 3-wk decrease lowered the level of milk production by 2.8 kg of 4% FCM/d in the first 84 d of the subsequent lactation, whereas a 3-wk increase raised the level of milk production by .5 kg/d. In the first 168 d......The effect of planned dry period lengths of 4, 7, and 10 wk on subsequent lactational yield was estimated with 366 cows in an experiment in which dry period was manipulated independently of milk yield prior to drying off. In two herds, all three treatments were compared within herd; in six herds...... of the subsequent lactation, the difference between 4-wk and 7-wk planned dry periods was 2.7 kg/d, and the difference between 7- and 10-wk periods was .4 kg/d. There was no indication of interaction among planned dry period length and lactation number, days open in previous lactation, previous milk yield, breed...

The associations among prior drinking consequences, subjective evaluations, and subsequent alcohol outcomes.

Science.gov (United States)

Zaso, Michelle J; Park, Aesoon; Kim, Jueun; Gellis, Les A; Kwon, Hoin; Maisto, Stephen A

2016-05-01

Although the many positive and negative psychosocial consequences of alcohol use are well documented, evidence of the association between prior drinking consequences and subsequent alcohol-related outcomes is mixed. Social learning theory highlights that cognitive appraisals of prior drinking consequences play a crucial intermediate role in the relation of prior drinking consequences with subsequent alcohol-related outcomes. This prospective study was designed to test the mediating effects of subjective evaluations (i.e., perceived valence and controllability) in the association of prior drinking consequences with change in binge drinking and drinking consequences over time. Participants were 171 college students (69% female, 74% White, M age = 18.95 years, SD = 1.35) who completed 2 online surveys, with an average interval of 68 days (SD = 10.22) between assessments. Path analyses of the data did not support mediational effects of perceived valence or controllability of prior drinking consequences on subsequent alcohol-related outcomes. Specifically, greater frequency of negative consequences was associated with lower perceived valence and controllability, and greater frequency of positive consequences was associated with lower perceived controllability of the experienced consequences. However, perceptions of valence and controllability were not in turn associated with subsequent binge drinking and drinking consequences. Instead, greater frequency of positive consequences was directly associated with greater subsequent frequency of binge drinking. Findings highlight the importance of prior positive consequences in the escalation of binge drinking over a short period of time, although this relation may not be accounted for by perceptions of valence and controllability of the prior drinking consequences. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Cognitive predictors and moderators of winter depression treatment outcomes in cognitive-behavioral therapy vs. light therapy.

Science.gov (United States)

Sitnikov, Lilya; Rohan, Kelly J; Evans, Maggie; Mahon, Jennifer N; Nillni, Yael I

2013-12-01

There is no empirical basis for determining which seasonal affective disorder (SAD) patients are best suited for what type of treatment. Using data from a parent clinical trial comparing light therapy (LT), cognitive-behavioral therapy (CBT), and their combination (CBT + LT) for SAD, we constructed hierarchical linear regression models to explore baseline cognitive vulnerability constructs (i.e., dysfunctional attitudes, negative automatic thoughts, response styles) as prognostic and prescriptive factors of acute and next winter depression outcomes. Cognitive constructs did not predict or moderate acute treatment outcomes. Baseline dysfunctional attitudes and negative automatic thoughts were prescriptive of next winter treatment outcomes. Participants with higher baseline levels of dysfunctional attitudes and negative automatic thoughts had less severe depression the next winter if treated with CBT than if treated with LT. In addition, participants randomized to solo LT who scored at or above the sample mean on these cognitive measures at baseline had more severe depressive symptoms the next winter relative to those who scored below the mean. Baseline dysfunctional attitudes and negative automatic thoughts did not predict treatment outcomes in participants assigned to solo CBT or CBT + LT. Therefore, SAD patients with extremely rigid cognitions did not fare as well in the subsequent winter if treated initially with solo LT. Such patients may be better suited for initial treatment with CBT, which directly targets cognitive vulnerability processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Common Characteristics of Improvisational Approaches in Music Therapy for Children with Autism Spectrum Disorder: Developing Treatment Guidelines.

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Geretsegger, Monika; Holck, Ulla; Carpente, John A; Elefant, Cochavit; Kim, Jinah; Gold, Christian

2015-01-01

Improvisational methods of music therapy have been increasingly applied in the treatment of individuals with autism spectrum disorder (ASD) over the past decades in many countries worldwide. This study aimed at developing treatment guidelines based on the most important common characteristics of improvisational music therapy (IMT) with children affected by ASD as applied across various countries and theoretical backgrounds. After initial development of treatment principle items, a survey among music therapy professionals in 10 countries and focus group workshops with experienced clinicians in three countries were conducted to evaluate the items and formulate revised treatment guidelines. To check usability, a treatment fidelity assessment tool was subsequently used to rate therapy excerpts. Survey findings and feedback from the focus groups corroborated most of the initial principles for IMT in the context of children with ASD. Unique and essential principles include facilitating musical and emotional attunement, musically scaffolding the flow of interaction, and tapping into the shared history of musical interaction between child and therapist. Raters successfully used the tool to evaluate treatment adherence and competence. Summarizing an international consensus about core principles of improvisational approaches in music therapy for children with ASD, these treatment guidelines may be applied in diverse theoretical models of music therapy. They can be used to assess treatment fidelity, and may be applied to facilitate future research, clinical practice, and training. © the American Music Therapy Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Emotion regulation during the encoding of emotional stimuli: Effects on subsequent memory.

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Leventon, Jacqueline S; Bauer, Patricia J

2016-02-01

In the adult literature, emotional arousal is regarded as a source of the enhancing effect of emotion on subsequent memory. Here, we used behavioral and electrophysiological methods to examine the role of emotional arousal on subsequent memory in school-age children. Furthermore, we implemented a reappraisal instruction to manipulate (down-regulate) emotional arousal at encoding to examine the relation between emotional arousal and subsequent memory. Participants (8-year-old girls) viewed emotional scenes as electrophysiological (EEG) data were recorded and participated in a memory task 1 to 5days later where EEG and behavioral responses were recorded; participants provided subjective ratings of the scenes after the memory task. The reappraisal instruction successfully reduced emotional arousal responses to negative stimuli but not positive stimuli. Similarly, recognition performance in both event-related potentials (ERPs) and behavior was impaired for reappraised negative stimuli but not positive stimuli. The findings indicate that ERPs are sensitive to the reappraisal of negative stimuli in children as young as 8years. Furthermore, the findings suggest an interaction of emotion and memory during the school years, implicating the explanatory role of emotional arousal at encoding on subsequent memory performance in female children as young as 8years. Copyright © 2015 Elsevier Inc. All rights reserved.

Patient compliance and supportive periodontal therapy: Study among young adults of Namakkal district

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Subramanium Gokulanathan

2014-01-01

Full Text Available Aims: The aim of this study is to assess the patient compliance to supportive and maintenance periodontal therapy and to determine the reason for noncompliance among young adult patients of Namakkal district, India. Materials and Methods: This was a cross-sectional study conducted on 400 patients who underwent periodontal therapy and subsequently recalled for supportive and maintenance periodontal treatment in the Department of Periodontics, Vivekanandha Dental College for Women, Namakkal. Patients age group 25-35 years and of both gender were equally selected and grouped by occupation and socioeconomic status. According to their compliance with appointments, they are categorized as complete compliance, partially compliance and insufficient or noncompliance. Noncompliance and partially compliance patients were contacted and asked to rate their experience and reason for noncompliance. Results: In this study, 80% of patients showed complete compliance and were regular for supportive periodontal therapy appointments. Women were more regular in maintaining recall appointments than men. Salaried employers showed 84.3% complete compliance, while self-employed personals showed 77% complete compliance and 75% of nonworking personals were regular to the appointment schedule. Noncompliance person has quoted lack of time and forgetting the appointment date as a major reason for missed appointments. Conclusions: This study recommends the need for improvement in communication skills of practitioners and weekend appointment for patient undergoing periodontal maintenance therapy.

Intra-Carotid Urokinase thrombolytic therapy in acute cerebral infarction: a preliminary study

International Nuclear Information System (INIS)

Cho, Hee Kyung; Chung, Tae Sub; Kim, Dong Ik; Suh, Jung Ho; Lee, Byung In; Lee, Byung Chul

1990-01-01

We conducted a pilot study to evaluate the possibility that the intraarterial thrombolytic therapy might lead to recanalization of the acutely occluded cerebral arteries and subsequent clinical improvement in patients with acute cerebral infarction. Mean time from the onset of symptoms to the start of treatment and mean dosage of thrombolytic agent, Urokinase, were 6.4 hours and 1,260,000 units, respectively. Seven of 12 cases (58%) with acute cerebral infarction demonstrated successful recanalization. Neurological evaluation at one week and three months after the onset of symptoms suggested better outcome in the cases with recanalization. Repeat CT scan at 24 hours and one week after the procedure demonstrated the evidence of hemorrhagic infarction in the infarcted territories in five cases (41%), but clinical deteriorations were observed in only 2 cases. Though statistical analysis could not be done because the limited number of cases, these results suggest that the intraarterial thrombolytic therapy had a role in the management of acute cerebral infarction

Evolution of echocardiography in subclinical detection of cancer therapy-related cardiac dysfunction.

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Moudgil, Rohit; Hassan, Saamir; Palaskas, Nicolas; Lopez-Mattei, Juan; Banchs, Jose; Yusuf, Syed Wamique

2018-05-11

Cancer therapies have resulted in increased survivorship in oncological patients. However, the benefits have been marred by the development of premature cardiovascular disease. The current definition outlines measurement of ejection fraction as a mean to diagnose cancer therapeutic-related cardiac dysfunction (CTRCD); however, up to 58% of the patients do not regain their cardiac function after the CTRCD diagnosis, despite therapeutic interventions. Therefore, there has been a growing interest in the markers for early myocardial changes (ie, changes with normal left ventricular ejection fraction [LVEF]) that may predict the development of subsequent left ventricular ejection fraction reduction or progression to heart failure. This review will highlight the use of diastolic parameters, tissue Doppler imaging (TDI), and speckle tracking echocardiogram (STE) as emerging technologies which can potentially detect cardiac dysfunction thereby stratifying patients for cardioprotective therapies. The goal of this manuscript was to highlight the concepts and discuss the current controversies surrounding these echocardiographic imaging modalities. © 2018 Wiley Periodicals, Inc.

INNOLAB- image guided surgery and therapy lab

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Fritzsche Holger

2017-09-01

Full Text Available Incremental innovation, something better or cheaper or more effective, is the standard innovation process for medical product development. Disruptive innovation is often not recognized as disruptive, because it very often starts as a simple and easy alternative to existing products with much reduced features and bad performance. Innovation is the invention multiplied with a commercial use, or in other words something that eventually provides a value to a clinical user or patient. To create such innovation not a technology push (technology delivered from a technical need perspective but rather a pull (by learning and working with the clinical users is required. Medical technology students need to understand that only through proper observation, procedure know-how and subsequent analysis and evaluation, clinically relevant and affordable innovation can be generated and possibly subsequently used for entrepreneurial ventures. The dedicated laboratory for innovation, research and entrepreneurship- INNOLAB ego.-INKUBATOR IGT (Image Guided Therapies is financed by the state of Sachsen-Anhalt as part of the European ego.-INKUBATOR program with (EFRE funds at the university clinic operated by the technical chair for catheter technologies and image guided surgeries. It forms a network node between medicine, research and economics. It teaches students to lead innovation processes, technology transfer to the user and is designed to stimulate the start-up intentions.

Progress in the Full-Text Publication Rate of Orthopaedic and Sport Physical Therapy Abstracts Presented at the American Physical Therapy Association's Combined Sections Meeting.

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Warden, Stuart J; Fletcher, Jacquelyn M; Barker, Rick G; Guildenbecher, Elizabeth A; Gorkis, Colleen E; Thompson, William R

2017-10-07

Study Design Descriptive study. Background Professional meetings, such as the American Physical Therapy Association's (APTA's) Combined Sections Meeting (CSM), provide forums for sharing information. However, it was reported that only one-quarter of orthopaedic and sports physical therapy abstracts presented at the CSM between 2000 and 2004 went on to full-text publication. This low conversion rate raises a number of concerns regarding the full dissemination of work within the profession. Objectives The purpose of this study was to determine the full-text publication rate of work presented in abstract form at subsequent CSMs and investigate factors influencing the rate. Methods A systematic search was undertaken to locate full-text publications of orthopaedic and sports physical therapy abstracts presented at CSMs between 2005 and 2011. Eligible publications were published within 5 years following abstract presentation. The influences of year of abstract presentation, APTA section, presentation type, institution of origin, study design, and study significance were assessed. Results Over one-third (38.6%) of presented abstracts progressed to full-text publication. Odds of full-text publication increased if the abstract was presented as a platform presentation, originated from a doctorate-granting institution, reported findings of an experimental study, or reported a statistically significant finding. Conclusion The full-text publication rate for orthopaedic and sports physical therapy abstracts presented at recent CSMs has increased by over 50% compared to that reported for the preceding period. The rate is now in the range of that reported in comparable clinical disciplines, demonstrating important progress in the full dissemination of work within the profession. J Orthop Sports Phys Ther, Epub 7 Oct 2017. doi:10.2519/jospt.2018.7581.

Sustained mental workload does not affect subsequent sleep intensity

NARCIS (Netherlands)

de Bruin, EA; Beersma, DGM; Daan, S; Bruin, Eveline A. de

Mental activity is a neglected factor in sleep research. The few investigations on sleep that manipulate prior mental activity are inconclusive with respect to the possible effects of mental activity on recovery. In the present study, the effects of two levels of mental activity on subsequent sleep

Phase II Trial of Atezolizumab As First-Line or Subsequent Therapy for Patients With Programmed Death-Ligand 1-Selected Advanced Non-Small-Cell Lung Cancer (BIRCH)

NARCIS (Netherlands)

Peters, S.; Gettinger, S.; Johnson, M.L.; Janne, P.A.; Garassino, M.C.; Christoph, D.; Toh, C.K.; Rizvi, N.A.; Chaft, J.E.; Costa, E.; Patel, J.D.; Chow, L.Q.M.; Koczywas, M.; Ho, C.; Fruh, M.; Heuvel, M. van den; Rothenstein, J.; Reck, M.; Paz-Ares, L.; Shepherd, F.A.; Kurata, T.; Li, Z.; Qiu, J.; Kowanetz, M.; Mocci, S.; Shankar, G.; Sandler, A.; Felip, E.

2017-01-01

Purpose BIRCH was designed to examine the efficacy of atezolizumab, a humanized anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, in advanced non-small-cell lung cancer (NSCLC) across lines of therapy. Patients were selected on the basis of PD-L1 expression on tumor cells (TC) or

Panhypopituitarism arising after radiation therapy for germinoma in the suprasellar region. Case report

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Maeyama, Masataka; Toribe, Yasuhisa; Adachi, Kouichi; Arita, Kouji [Itami Municipal Hospital, Hyogo (Japan)

1995-01-01

A case is presented in which panhypopituitarism occurred in an 8-year-old girl after radiation therapy for germinoma in the suprasellar region. The patient was referred to the hospital because of polydipsia and polyhydruria. She was diagnosed as having pituitary diabetes insipidus by water limitation test. Cranial CT and MRI revealed germinoma in the suprasellar region. Tumor cells were remarkably reduced by tentative irradiation. Thus the patient was treated with whole-body irradiation. Subsequently, she had general fatigue, loss of appetite, and activity decrease. The reaction to TRH test was low. ACTH secretion insufficiency was revealed by insulin test. The patient developed panhypopituitarism associated with GH and ADH secretion insufficiency. She has been managed on hormonal therapy, including DDAVP, hydrocortisone, and Levothyroxine. Although germinoma is highly sensitive to radiation, a long-term follow up is required because of the potential occurrence of postoperative sequelae. (N.K.).

Panhypopituitarism arising after radiation therapy for germinoma in the suprasellar region. Case report

International Nuclear Information System (INIS)

Maeyama, Masataka; Toribe, Yasuhisa; Adachi, Kouichi; Arita, Kouji

1995-01-01

A case is presented in which panhypopituitarism occurred in an 8-year-old girl after radiation therapy for germinoma in the suprasellar region. The patient was referred to the hospital because of polydipsia and polyhydruria. She was diagnosed as having pituitary diabetes insipidus by water limitation test. Cranial CT and MRI revealed germinoma in the suprasellar region. Tumor cells were remarkably reduced by tentative irradiation. Thus the patient was treated with whole-body irradiation. Subsequently, she had general fatigue, loss of appetite, and activity decrease. The reaction to TRH test was low. ACTH secretion insufficiency was revealed by insulin test. The patient developed panhypopituitarism associated with GH and ADH secretion insufficiency. She has been managed on hormonal therapy, including DDAVP, hydrocortisone, and Levothyroxine. Although germinoma is highly sensitive to radiation, a long-term follow up is required because of the potential occurrence of postoperative sequelae. (N.K.)

Family Therapy

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Family therapy Overview Family therapy is a type of psychological counseling (psychotherapy) that can help family members improve communication and resolve conflicts. Family therapy is usually provided by a psychologist, ...

Histopathologic changes in fallopian tubes subsequent to sterilization procedures.

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Stock, R J

1983-01-01

Longitudinal serial and serial step sections of fallopian tubes from more than 100 patients, subsequent to tubal sterilization procedures, were examined. Thirteen of these patients had pregnancies following their sterilizations. The histologic findings at the previous surgical sites were compatible with what would be expected for a normal healing process. Evidence for a unique tubal epithelial process, as suggested by the terms "endosalpingiosis" or "recanalization," was lacking. Likewise, the author found no evidence of tuboperitoneal fistula formation and/or the subsequent occurrence of pregnancy secondary to localized endometriosis. The histologic notations of proximal luminal dilatation, plical attenuation, chronic inflammatory infiltrates with pseudopolyp formation, and the findings of plical thickening in the distal segment of remaining tube after an interruption type of procedure seem to be associated with the length of time from the sterilization procedure. These may be factors related to the apparent reduced success rate, with time, of microsurgical reanastomotic procedures.

Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy

Energy Technology Data Exchange (ETDEWEB)

Tokumaru, Sunao; Yoshikai, Tomonori; Uchino, Akira; Kudo, Sho [Dept. of Radiology, Saga Medical School (Japan); Matsui, Makoto; Kuroda, Yasuo [Dept. of Neurology, Saga Medical School (Japan)

2001-12-01

We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases. (orig.)

Technetium-99m-ECD SPECT in antiphospholipid antibody syndrome: a drastic improvement in brain perfusion by antiplatelet therapy

International Nuclear Information System (INIS)

Tokumaru, Sunao; Yoshikai, Tomonori; Uchino, Akira; Kudo, Sho; Matsui, Makoto; Kuroda, Yasuo

2001-01-01

We present a case of antiphospholipid antibody syndrome (APS) with repeated transient ischemic attacks (TIAs). Magnetic resonance imaging showed multiple cerebral infarcts and ischemic changes in the cerebral white matter. Cerebral angiographies showed no abnormalities. Technetium-99m-ethyl cysteinate dimer (Tc-99m-ECD) brain SPECT showed multiple decreased perfusion areas, which were more extensive than the lesions demonstrated on MRI. After treatment with an antiplatelet agent, the patient subsequently recovered from the TIAs. Although no interval changes were observed by MRI after therapy, follow-up Tc-99m-ECD SPECT revealed a marked improvement in brain perfusion. This is the first imaging report of remarkable post-therapy improvement in brain perfusion in APS cases. (orig.)

Implementing cognitive therapies into routine psychosis care: organisational foundations.

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Dark, Frances; Whiteford, Harvey; Ashkanasy, Neal M; Harvey, Carol; Crompton, David; Newman, Ellie

2015-08-05

Treatment outcomes for people diagnosed with psychosis remain suboptimal due in part to the limited systematic application of evidence based practice (Adm Policy Ment Health, 36: 1-7, 2009) [1]. The Implementation science literature identifies a number of factors organisationally that need to be considered when planning to introduce a particular EBP. Profiling these organisational characteristics at baseline, prior to commencement of service reform can determine the focus of a subsequent implementation plan. This study examined the organisational baseline factors existing in two services promoting the routine use of cognitive interventions for psychosis. One of the services studied has since undertaken organisational structural reform to facilitate the greater uptake of Evidence Based Practice (EBP). The results of this study were used to design an implementation strategy to make cognitive therapies a part of routine psychosis care. One hundred-and-six mental health staff from two metropolitan mental health services in Australia was surveyed to ascertain their attitudes, competencies and interest in Cognitive Behavioural Therapy for psychosis (CBTp) and Cognitive Remediation Therapy (CRT). In addition perceptions of organisational values were profiled using the Organisational Culture Profile (OCP). Fifty five participants were excluded because they completed less than 50% of the survey. The final sample consisted of 51 participants. 48.1% of surveys were completed. Over 50% of staff were interested in CBTp and CRT approaches to psychosis. Staff were aware of existing CBTp and CRT programs but these were not uniformly available throughout the services. Fourteen percent of staff identified as CBT therapist and 35% were trained CRT facilitators. Only 12% of staff were receiving therapy specific supervision. The Organisational Culture Profile (OCP) at baseline revealed highest scores amongst leadership, planning, and humanistic workplace domains, with communication

Retroperitoneal abscess shortly after chemotherapy for lung cancer: A case report.

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Ohara, Gen; Kondo, Tadashi; Kagohashi, Katsunori; Watanabe, Hiroko; Kawaguchi, Mio; Kurishima, Koichi; Satoh, Hiroaki; Hizawa, Nobuyuki

2014-03-01

To the best of our knowledge, the formation of a retroperitoneal abscess due to acute appendicitis shortly after administration of chemotherapy for lung cancer has not been previously reported. This is the case report of a 59-year-old male who was admitted to the Mito Medical Center (Mito, Japan) and diagnosed with lung adenocarcinoma with pleuritis carcinomatosis. Although no distant metastasis was identified, combination chemotherapy with cisplatin and pemetrexed was administered. Nine days after initiating chemotherapy, the patient developed right lower quadrant abdominal pain and high fever. Computed tomography (CT) of the abdomen and pelvis revealed the collection of gas and fluid in the retroperitoneum adjacent to the cecum. The abscess was locally drained; however, the infection continued to spread, with subsequent development of a scrotal abscess. Consequently, appendectomy was performed. The patient recovered well and the lung adenocarcinoma was treated with additional courses of chemotherapy following the remission of the local inflammation. Retroperitoneal abscess due to acute appendicitis is an unusual finding; however, this rare complication should be considered during or shortly after chemotherapy in patients with lung cancer.

Occupation and the relevance of primatology to occupational therapy.

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Wood, W

1993-06-01

The adaptive functions of occupation during the phylogenetic history of the human species and the ontogenetic development of individual primates re examined through a review of relevant research of wild and captive nonhuman primates. This review suggests that the effectiveness of occupation as a therapeutic medium throughout life span development is fundamentally tied to humankind's phylogenetic history. It is accordingly argued that there is considerable justification to maintain occupational therapy's historical commitment to therapeutic occupation as the profession's primary treatment modality. To support this commitment, questions to guide practice and research are identified that emanate from the primate literature and that are highly germane to the therapeutic process in occupational therapy. These questions address: (a) the relationship between the press of the various environments in which occupational therapists practice and subsequent opportunities availed to patients for engagement in occupation; (b) the relationship between the extent to which patients are or are not empowered to exert real control over their use of time and their eventual development of disabling conditions; and (c) the therapeutic efficacy of occupation as compared with other treatment approaches that are not comparably holistic.

Experience in the management of ECMO therapy as a mortality risk factor.