Potential of dose optimisation in MRI-based PDR brachytherapy of cervix carcinoma

BACKGROUND AND PURPOSE: In this study on PDR treatment planning of utero-vaginal carcinoma, we analysed the dosimetry of traditional X-ray based plans as it presents on MR images. The potential gain of MRI-based dose optimisation was assessed. PATIENTS AND METHODS: Sixteen patients boosted with PDR brachytherapy after external beam therapy were included. The clinical X-ray based plans were projected on MR images. The GTV, HR-CTV and IR-CTV were retrospectively contoured, as well as the bladder, rectum and sigmoid colon. The dose in the critical organs and target coverage was investigated. In a second phase, the plans were manually optimised using the MR information. The objectives were to lower the dose in the critical organs (85Gy(alphabeta3) for bladder, 75Gy(alphabeta3) for rectum and sigmoid colon) and to increase the HR-CTV dose to D9085Gy(alphabeta10). RESULTS: In the X-ray based plans, D(2cc) in bladder and sigmoid colon exceeded the tolerance doses in 10/16 and 7/16 patients, respectively. Coverage of the IR-CTV with the 60Gy(alphabeta10) was acceptable. D90 of the HR-CTV was below 85Gy(alphabeta10) in 13 out of 16 patients. After optimisation, the dose constraints in the OAR were not exceeded anymore in any patient. The average D(2cc) dose reduction was 7+/-6Gy(alphabeta3) in the bladder and 7+/-4Gy(alphabeta3) in the sigmoid colon for those patients in which the dose constraint was initially exceeded. In addition, an average dose increase of 3Gy(alphabeta10) was accomplished in the HR-CTV. CONCLUSIONS: MRI-based dose optimisation can play an important role to reduce the dose delivered to the critical organs and to improve target coverage.     

Apparent coactivation due to interference of expression constructs with nuclear receptor expression

Transient cotransfection in COS-7 cells, a standard approach to demonstrate coactivation, was used to study the coactivation properties of NuRIP183, a new nuclear receptor interacting protein of 183 kDa, isolated by a yeast two-hybrid screening. Transfection with a NuRIP183 expression construct strongly increased the ligand-dependent response of reporter constructs for several nuclear receptors when compared to transfection with the empty expression vector. A more detailed study, however, revealed major changes in the expression level of the nuclear receptors in cotransfection experiments, indicating that the observed changes in receptor activity were not due to coactivation but to differences in receptor concentration caused by interference from the cotransfected expression constructs with the expression of the receptor. Such interference, which is inversely related to the length of the insert, was observed, not only in COS-7 cells but also in CV-1 and MCF-7 cells, using different transfection techniques (FuGENE-6 and calcium phosphate) and different expression vectors (pSG5, pcDNA1.1 and pIRESneo). These data cast some doubt on coactivation of nuclear receptors based on similar cotransfection experiments without measurement of receptor concentration. Moreover, it is recommended to limit the amounts of (co)transfected expression plasmid and to avoid the use of empty expression plasmid as a control. Finally, one should be aware of similar misleading results in other experimental set-ups based on cotransfection.     

Is phenytoin contraindicated in patients receiving cranial irradiation ?

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation.     

氨溴索治疗小儿毛细支气管炎77例

1临床资料2002-01／2004-02收治临床症状典型且无并发症毛细支气管炎患儿116例，发病年龄3-24(平均8．4)mo，男61例，女55例，按就诊时间顺序分为氨溴索雾化吸入组(观察组)、氨溴索静脉点滴组(对照Ⅰ组)和常规治疗组(对照Ⅱ组)，分别为38，39，39例．常规治疗组给予头孢噻肟钠50mg／kg，2／d及穿琥宁80-120mg／d分别静脉滴注及对症治疗(如吸氧、镇静、退热等处理)；观察组在常规治疗的基础上加用氨溴索4mg加生理盐水10mL超声雾化吸入10～15min，2／d；     

Airway and body surface sensors for triggering in neonatal ventilation

Failure of neonatal patient triggered ventilation may reflect a delay in delivery of flow relative to the inspiratory effort of the infant. Transmission of diaphragmatic contraction to the sensor site (patient delay) and further transmission to and within the sensing device (device delay) both contribute to the delay in triggering. Patient and device delays were studied for different sensing systems in 36 infants, 24 of whom were intubated. Device delay was long (<40 ms) with a conventional apnoea monitor compared with sensors placed at the airway opening (2 ms), the inspiratory (12 ms) and expiratory (3 ms) pressure transducers of the ventilator, the Graseby capsule (8 ms), strain gauges (3 ms) and oesophageal pressure (6 ms). In near normal infants, the sum of patient and device delays for the latter sensors was less than 20 ms and a minor component of the total delay. However, in severe lung disease the total delay may be more than 100ms even for airway sensors.     

Post-transplant Lymphoproliferative Disorders: Implications for Acquired Immunodeficiency Syndrome-Associated Malignancies

Post-transplant lymphoproliferative disorders (PTLDs) comprisea histologic spectrum, ranging from hyperplastic-appearing lesionsto frank non-Hodgkin's lymphoma or multiple myeloma histology.Multiple clones may coexist, each representing a discrete lymphomagenicevent, a situation that is unique to immunodeficiency states.The incidence varies from 1% in renal recipients to 5% in heartrecipients, but can be markedly increased by the use of anti-T-celltherapies or by T-cell depletion in bone marrow transplantation.PTLD continues to arise, even many years after transplantation,and late T-cell lymphomas have recently been recognized. PretransplantEpstein-Barr virus (EBV) seronegativity increases risk to ashigh as 30%–50%. PTLD has a highly variable clinical picture;certain patterns are, however, seen. Reversibility of PTLD withreduction in immunosuppressives has long been recognized. Predictingreversibility has been difficult. The presence or absence ofbcl-6 mutations has recently been identified as being of predictivevalue. Surgical resection can be curative. Cytotoxics, althoughproblematic, can also be curative. Long-term remission has beenachieved with anti CD21 and CD24 antibodies; efficacy has beenreported for interferon alfa and for rituximab. In vitro expandedEBV-specific T cells have been effective as treatment and asprophylaxis in the setting of bone marrow transplantation. EBVviral load measured in blood appears to associate with the emergenceof PTLD and may facilitate prophylactic studies. PTLD is a modelof immunodeficiency-related EBV lymphomagenesis. Pathogenetic,therapeutic, and prophylactic insights gained from the studyof PTLD are likely to be applicable to the acquired immunodeficiencysyndrome setting.