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101.
Mixed micellar nanoparticle of amphotericin b and poly styrene-block-poly ethylene oxide reduces nephrotoxicity but retains antifungal activity 总被引:1,自引:0,他引:1
Han K Miah MA Shanmugam S Yong CS Choi HG Kim JA Yoo BK 《Archives of pharmacal research》2007,30(10):1344-1349
Mixed micellar nanoparticle consisting of amphotericin B (AmB) and poly styrene-block-poly ethylene oxide (PS-block-PEO) was prepared by high pressure homogenizer. Nephrotoxicity of the nanoparticle was investigated along with antifungal activity and self-aggregation status of the drug in the nanoparticle. Nephrotoxicity was markedly reduced when AmB was intravenously administered to rats as mixed micellar nanoparticle with PS-block-PEO in terms of transmission electron microscopy of tubular cells and creatinine clearance. Antifungal activity of AmB was not altered when the drug was in the form of mixed micellar nanoparticle compared to both conventional formulation and AmB micelle treated by same procedure without PS-block-PEO. Self-aggregation status of AmB molecules revealed monomeric in the mixed micellar nanoparticle with PS-block-PEO up to the therapeutic level of the drug (1-3 mM). The reduced nephrotoxicity of AmB in mixed micellar nanoparticle may be associated with the existence of the drug as monomeric form in the nanoparticle. Based on our result, formulation of AmB as mixed micellar nanoparticle with PS-block-PEO may be a promising alternative for the treatment of fungal diseases in patients who are at risk of renal dysfunction. 相似文献
102.
Vorstand und AG Angeborene Herzfehler/Kinderherzchirurgie der DGTHG 《The Thoracic and cardiovascular surgeon》2006,54(2):73-77
The "Working Group for Congenital Heart Surgery and Pediatric Heart Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS) has analysed and recommended structures for congenital heart surgery departments in Germany. The document was worked out according to a similar paper approved earlier by the European Association for Cardio-thoracic Surgery (EACTS). The "Working Group" unifies the majority of cardiac surgeons involved in congenital heart surgery in Germany. Current structures of cardiac centers vary. Therefore the aim of this document is to elucidate additional structural needs for both highly specialized institutions and those for standard care. Specialized centers should allow for treatment of newborns and adult patients with congenital heart disease, include implementation of assist devices and transplantation, possess research facilities and ensure highest standards of education and training. Standard care units do not necessarily need to cater for the above mentioned spectrum. However, the evaluation of quality of care should be given priority in all centers involved in care of patients with congenital heart disease. Data acquisition and transfer must be guaranteed to both the GSTCVS and EACTS in order to ensure national and international comparison of surgical results. This may also give further guidance for improved patient care. 相似文献
103.
Attila?KollàrEmail author Marco?Maruzzo Christina?Messiou Elisabeth?Cartwright Aisha?Miah Juan?Martin-Liberal Khin?Thway Ellen?McGrath Alison?Dunlop Komel?Khabra Beatrice?Seddon Palma?Dileo Mark?Linch Ian?Judson Charlotte?Benson 《Clinical sarcoma research》2014,4(1):17
Background
Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of gastrointestinalstromal tumors (GIST) although most patients develop resistance to first and second-line therapies.Regorafenib, an oral multi-targeted TKI, has demonstrated benefit in previously treated GIST patients.Methods
We assessed safety and activity of regorafenib in patients treated within the Managed Access Program (MAP). All consecutive patients with advanced GIST who had progressed on or were intolerant to imatinib and sunitinib were recruited from the Royal Marsden and University College Hospitals. We retrospectively reviewed the data for response, toxicity, treatment duration and survival. Response was assessed by RECIST and Choi criteria. Toxicity was graded according to CTCAE v4.0 criteria.Results
20 patients were included in the MAP in the UK between 3/2013 and 9/2013. Median age was 68 (range 45–87), 65% of patients were male. Performance Status was 0–1 for 18 patients (90%), 2 for 2 patients (10%). The median treatment duration was 9.25 months (range 0.1-15.33). 18 patients were assessable for response and all patients attained a best response of at least stable disease. At a median follow-up of 12.6 months, there were 2 partial responses (11%) by RECIST and 7 partial responses (39%) according to Choi criteria. 7 patients remain on regorafenib. 3 patients discontinued treatment due to unacceptable adverse events; fistulation, myalgia and fatigue. 10 (50%) patients had grade 3 toxicities and 11 (55%) patients required a dose reduction. Median PFS was 9.4 months (95% Cl: 6.2-not calculable) and median OS was 12.2 months (95% Cl: 10.5-not calculable). Notably, prolonged stable disease was seen in 1 patient with exon 9 mutation and 1 patient with PDGFR D842V mutation.Conclusions
These data demonstrate encouraging activity and tolerability of regorafenib in routine clinical practice. The documented adverse events are in line with previous trial data.104.
105.
Pre‐ and Postoperative Chemotherapy in Localized Extremity Soft Tissue Sarcoma: A European Organization for Research and Treatment of Cancer Expert Survey
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106.
Winston Chew Charlotte Benson Khin Thway Andrew Hayes Aisha Miah Shane Zaidi Alex T. J. Lee Christina Messiou Cyril Fisher Winette T. van der Graaf Robin L. Jones 《Medical oncology (Northwood, London, England)》2018,35(11):138
Background
Sclerosing epithelioid fibrosarcoma (SEF) is a very rare soft tissue sarcoma subtype. Clinically it is an aggressive tumour; however, to our knowledge there are no published reports regarding the efficacy of chemotherapy in SEF. Therefore, the aim of this study was to document the outcome of a series of patients with SEF treated at a single referral centre with reference to systemic therapy.Methods
A retrospective search of a prospectively maintained database was performed to identify all patients diagnosed with SEF between 1990 and 2017. The diagnosis was confirmed in each case by a dedicated soft tissue sarcoma pathologist. We analysed those with recurrent disease and the effect of systemic chemotherapy in the metastatic setting.Results
Thirteen patients were identified, median overall survival from diagnosis and metastasis were 47.3 (95% CI 25.0–131.9) and 16.3 (95% CI 5.3–20.6) months, respectively. In total, 12 (92.3%) patients developed metastatic disease of which 10 died of disease, 1 was lost to follow-up and 1 had recently commenced palliative treatment. Among the 10 patients with metastatic disease, 7 received palliative chemotherapy. Palliative chemotherapy resulted in partial response in 1 patient, stable disease in 3 patients and progressive disease in 3 patients. Median time to disease progression was 2.7 (95% CI 1.2–4.4) months. Two of 13 patients were treated with adjuvant chemotherapy, receiving 6 cycles of liposomal doxorubicin and 1 cycle of doxorubicin, respectively, with a metastasis-free survival of 28.2 and 7.1 months, respectively.Conclusion
SEF is an aggressive sarcoma subtype with a poor outcome and with limited responsiveness to conventional chemotherapy. Patients with this subtype should be considered for participation in clinical trials with novel agents. Further investigation into the biology of this rare disease is required to improve outcomes.107.
M. Libertini I. Mitra W. T. A. van der Graaf A. B. Miah I. Judson R. L. Jones K. Thomas E. Moskovic Z. Szucs C. Benson C. Messiou 《Clinical sarcoma research》2018,8(1):13
Background
One of the commonly used systemic agents for the treatment of aggressive fibromatosis is the anti-oestrogen drug tamoxifen. However, data on efficacy and optimum methods of response assessment are limited, consisting mainly of small case series and reports.Methods
A retrospective database was used to identify consecutive patients diagnosed with aggressive fibromatosis (AF) and treated with tamoxifen plus/minus non-steroidal anti-inflammatory drugs at our tertiary referral centre between 2007 and 2014. MRI and symptom changes were recorded.Results
Thirty-two patients (13 male 19 female, median age 41 years) were included. Median duration of treatment with tamoxifen was 316 days. Of 9 patients with progressive disease by RECIST 1.1 (28%): 4 patients experienced worsening symptoms; 3 patients had improved symptoms and 2 had no change in symptoms. Of 22 patients with stable disease (69%): 11 had no change in symptoms; 6 had improved symptoms and 5 patients had worsening symptoms. One patient achieved a partial response with improved symptoms.Conclusions
No relationship was identified between symptomatic benefit and response by RECIST 1.1 on MRI. Prospective studies in AF should incorporate endpoints focusing on patient symptoms.108.
Chowdhury SU Miah MA Mahmud MI Talukder SI Islam MN Islam N 《Mymensingh medical journal : MMJ》2008,17(2):192-196
A female 38 years old, housewife, presented to the Department of Dermatology and Venereology, Mymensingh Medical College Hospital (MMCH) on 08.04.07 with the complaints of i) pain and reduced movement of hand, knee, shoulder and neck joints for 1 year and 9 months ii) tightness of skin over face, neck, limbs and trunk for 1 year and 6 months iii) patchy depigmentation over same areas for 1 year and 3 months iv) deformity of hands with flexion contractures for 6 months and v) dysphagia to solid food for 3 months. She had no complaints of Raynaud's phenomenon. On general examination, she was ill looking, anemic and nutritionally poor. Examination of integumentary system showed smooth, shiny, thick, hard and hidebound skin with pigmentary alteration of 'salt and pepper' appearance over fingers, hands, limbs, face, neck and trunk. Hands appear claw like but more on the right side than the left and there were no other obvious changes suggestive of digital ischaemia (atrophy, ulceration, scarring, gangrene etc). Face has got suggestive features of scleroderma. Examination of the respiratory system showed restriction of chest movement and reduced expansibility of chest wall. No other abnormality was found on examination of other systems. Laboratory investigations showed histopathology typical of scleroderma. X-ray of hands and feet showed suggestive changes, lung function test-showed restrictive lung disease. Barium swallow x-ray of esophagus in supine position showed mild dilation of lower oesophagus. But serology was non-reactive (negative ANA, Negative RA test, Negative VDRL). So, she was diagnosed as a case of progressive systemic sclerosis (PSS) with some atypicality. 相似文献
109.
110.
Z Kibar S Salem CM Bosoi E Pauwels P De Marco E Merello AG Bassuk V Capra P Gros 《Clinical genetics》2011,80(1):76-82
Kibar Z, Salem S, Bosoi CM, Pauwels E, De Marco P, Merello E, Bassuk AG, Capra V, Gros P. Contribution of VANGL2 mutations to isolated neural tube defects. Vangl2 was identified as the gene defective in the Looptail (Lp) mouse model for neural tube defects (NTDs). This gene forms part of the planar cell polarity (PCP) pathway, also called the non‐canonical Frizzled/Dishevelled pathway, which mediates the morphogenetic process of convergent extension essential for proper gastrulation and neural tube formation in vertebrates. Genetic defects in PCP signaling have strongly been associated with NTDs in mouse models. To assess the role of VANGL2 in the complex etiology of NTDs in humans, we resequenced this gene in a large multi‐ethnic cohort of 673 familial and sporadic NTD patients, including 453 open spina bifida and 202 closed spinal NTD cases. Six novel rare missense mutations were identified in seven patients, five of which were affected with closed spinal NTDs. This suggests that VANGL2 mutations may predispose to NTDs in approximately 2.5% of closed spinal NTDs (5 in 202), at a frequency that is significantly different from that of 0.4% (2 in 453) detected in open spina bifida patients (p = 0.027). Our findings strongly implicate VANGL2 in the genetic causation of spinal NTDs in a subset of patients and provide additional evidence for a pathogenic role of PCP signaling in these malformations. 相似文献