Differentiation induction and growth factor responses of murine myeloid leukemias

Current therapeutic regimes for the treatment of acute myeloid leukaemia employ aggressive cytotoxic strategies which have limited success and are not suitable for all patients. Manipulating myeloid leukaemic cells according to their responses to pharmacologically tolerable agents rather than employing aggressive non specific cell kill would be desirable. Differentiation induction of myeloid leukaemic cells as an alternative therapeutic regime was evaluated. To elucidate the growth and differentiation abnormalities of myeloid leukaemic cells the differentiation induction and growth factor responses of bone marrow from three myeloid leukaemic models (SA2, SA7, SA8) and a leukaemic cell line (SA2 CL) were investigated in microtitre suspension cultures and compared with normal. The regulators of normal haemopoiesis occupy a key position in attempts to understand the nature of the abnormal state existing in myeloid leukaemia and could potentially play an important role therapeutically by suppressing myeloid leukaemic populations. To evaluate differentiation induction as an alternative therapeutic regime for the treatment of myeloid leukaemia both the physiological regulators and the differentiation inducer β-all trans retinoic acid (βatRA) alone and in combination with ara-C were investigated. The effects of these agents directly on the leukaemic clonogenic cell populations in vitro were measured following in vivo transplantation. The proliferative effects of WEHI-3B CM, as a source of IL-3, L929 CM as a source of M-CSF, and recombinant murine GM-CSF alone and in combination were investigated. Bone marrow cells from the SA7 and SA8 transplanted leukaemias were growth factor dependent for proliferation in vitro. The SA2 transplanted leukaemia proliferated autonomously at low passage numbers, the dominant leukaemic clone changed characteristics with progressive transplantation and became growth factor dependent at high passage numbers. A cell line (SA2 CL) was derived from leukaemic bone marrow cells of a low passage number of the SA2 leukaemia and proliferated at a high rate autonomously with minimal spontaneous differentiation in culture. The growth factor dependent leukaemias were induced to proliferate with each of the growth factors. No differences were observed in the dose response relationships between normal and leukaemic cells. Differences were observed in the proliferative rates, the day to which exponential cell growth was sustained in culture and the growth factor which induced maximal proliferation. WEHI-3B CM induced the maximal proliferative response of normal bone marrow cells and two of the leukaemias whereas rGM-CSF induced a maximal response of the third leukaemia. Leukaemic cells proliferated at a higher rate than normal cells in the first two to three days in culture but were not sustained in culture for as long as normal bone marrow cells. It appeared therefore, that in the case of some leukaemias the haemopoietic growth factors were effective at inducing a high initial but short term proliferative response of leukaemic cells and were more effective in sustaining normal bone marrow cells in vitro. (Abstract shortened by ProQuest.

Endovascular Closure of Ascending Aortic Pseudoaneurysm With a Type II Amplatzer Vascular Plug

A 71-year-old man initially presented with an asymptomatic, incidentally detected ascending aortic pseudoaneurysm 25 years following aortic root repair with mechanical aortic valve replacement. This pseudoaneurysm was previously treated with coil embolization but due to coil impaction it reopened 8 years later. Endovascular closure of the pseudoaneurysm was achieved with the off-label use of a type II Amplatzer vascular plu

Collaborative learning : an effective and enjoyable experience! a successful computer-facilitated environment for tertiary students

We have developed a collaborative learning environment (CLE) as a student-centred approach to lecture replacement, with a special focus on assisting students' learning of difficult concepts. The majority of the program is structured around cost-efficient web-delivered tutorials incorporating re-usable interactive components. These are supported by several stand-alone computer-based learning tutorials including ones that we developed to allow students to construct their own models of physiological mechanisms, together with computer-facilitated semester-long investigative projects to enhance their communication and critical reasoning skills. Each week for two hours during two semesters, students work in groups of three with an iMac computer. The computer-facilitated tasks are designed to support and extend their three weekly lectures by encouraging peer-learning and peer-teaching. In this article, the successful attributes of this collaborative learning environment are described and evaluated. In addition, relationships between the use of CLE and the students' approaches to learning are being investigated

A Prospective Pilot Study of the Safety and Effectiveness of Uterine Artery Embolization for the Treatment of Endometriosis: The UAE-E Study

Purpose Uterine artery embolization (UAE) evidence is increasing in the setting of adenomyosis, which shares pathological similarities to endometriosis. Endometriosis is characterized by the presence of endometrium-like tissue outside of the uterus, and the retrograde menstruation hypothesis may account for disease development. In women where fertility is no longer desired, hysterectomy can be offered to improve pain-related symptoms. The authors hypothesize that this cohort of patients may similarly respond to UAE. The aim of this pilot study is to assess the safety and effectiveness of UAE in the management of endometriosis-related symptoms. Methods Six-patient prospective single-arm pilot study in female, premenopausal patients over 40 years with symptoms of endometriosis. Institutional review board approval was obtained. Inclusion criteria include completed family, premenopausal, pelvic endometriosis as confirmed by laparoscopy within the last 5 years, and symptoms of endometriosis impacting quality of life as evidenced by the British Society of Gynaecological Endoscopy pelvic pain and Short Form-36 questionnaires. Results The primary endpoint will be safety, as assessed by the composite number of procedural and postprocedural complications during procedure, predischarge, and at 6 weeks, 3 months, 6 months, and 12 months. Secondary endpoints will include technical success, clinical success, and durability. Discussion This study will be a novel application of UAE in the setting of endometriosis and has the potential to improve patient quality of life. This pilot study will assess safety and allow the investigators to design a prospective randomized controlled study

The Safety of Continuing Therapeutic Anticoagulation During Inferior Vena Cava Filter Retrieval: A 6-Year Retrospective Review from a Tertiary Centre.

PURPOSE Assess the safety of inferior vena cava (IVC) filter retrieval in patients taking anticoagulation, compared to a non-anticoagulated cohort. MATERIALS AND METHODS Single-centre retrospective analysis of patients who underwent IVC filter retrieval between January 2012 and February 2018. Information about patient demographics, anticoagulation, tilt, major and minor complications was collected. Major complications were defined as: IVC injury from the filter retrieval, retained fragment of filter, filter fracture and filter embolisation. Minor complications were defined as: neck haematoma and puncture site infection. RESULTS Total of 357 patients (age 18-95, Male: 231) underwent IVC filter retrieval, comprising of Cook Celect Platinum, Cook Celect, and ALN-branded filters. Of these 182 patients were on anticoagulation and 175 patients were not on anticoagulation, based on the indication for the filter (thrombosis or prophylaxis) and at the discretion of the referring unit who were managing the anticoagulation. IVC filter retrieval was technically successful in 349 patients. Five major complications (1.4% of retrievals) were recorded and no minor complications (0% of retrievals). In the anticoagulation cohort, there were two major complications (1.1% of retrievals) both related to IVC injury. In the non-anticoagulated cohort, there were three major complications (1.7% of retrievals) relating to filter embolisation, IVC injury, and filter fracture. CONCLUSIONS IVC filter retrieval is a safe procedure with a low complication rate. Being on anticoagulation does not increase the risk of a major complication or change the management of major complication compared with a non-anticoagulated cohort. IVC filter retrieval is safe to perform in patients currently taking prophylactic or therapeutic anticoagulation based on our cohort. LEVEL OF EVIDENCE Level 3, retrospective cohort study