Peter Chu

Retrovirus-mediated gene transfer into human hematopoietic stem cells

Abstract Human hematopoietic stem cells genetically modified by retroviral-mediated gene transfer may offer new treatment options for patients with genetic disease. The potential of gene-modified hematopoietic stem cells as vehicles for gene delivery was first illustrated by the demonstration that hematopoietic systems of lethally irradiated mice can be reconstituted with retroviral vector transduced syngeneic bone marrow, and that these cells can in turn provide genetically marked progeny which persist in blood and marrow over extended time periods [1–4]. In contrast, hematopoietic stem cells from large animals prove difficult to transduce with retroviral vectors and are consequently less likely to function as vehicles for long-term gene therapy. Indeed, clinically relevant levels of gene transfer into large animal and human hematopoietic stem cells has not been widely achieved. The need for improved retroviral vector systems and for understanding the biology of hematopoietic stem cell gene transfer continue to fuel intense research activity. Preliminary results from human stem cell gene marking and gene therapy trials currently underway are encouraging. This contribution reviews the underlying concepts relevant to retroviral-mediated gene transfer into hematopoietic stem cells. We survey the evolution of approaches for gene transfer into hematopoietic stem cells, from murine and large animal models to the first human clinical trials. Finally, we discuss new strategies which are currently being pursued.

CT scanning for diagnosing blunt ureteral and ureteropelvic junction injuries

BackgroundBlunt ureteral and ureteropelvic (UPJ) injuries are extremely rare and very difficult to diagnose. Many of these injuries are missed by the initial trauma evaluation.MethodsTrauma registry data was used to identify all blunt trauma patients with ureteral or UPJ injuries, from 1 April 2001 to 30 November 2006. Demographics, injury information and outcomes were determined. Chart review was then performed to record initial clinical and all CT findings.ResultsEight patients had ureteral or UPJ injuries. Subtle findings such as perinephric stranding and hematomas, and low density retroperitoneal fluid were evident on all initial scans, and prompted delayed excretory scans in 7/8 cases. As a result, ureteral and UPJ injuries were diagnosed immediately for these seven patients. These findings were initially missed in the eighth patient because significant associated visceral findings mandated emergency laparotomy. All ureteral and UPJ injuries have completely healed except for the case with the delay in diagnosis.ConclusionMost blunt ureteral and UPJ injuries can be identified if delayed excretory CT scans are performed based on initial CT findings of perinephric stranding and hematomas, or the finding of low density retroperitoneal fluid.

Retrograde urethrocystography impairs computed tomography diagnosis of pelvic arterial hemorrhage in the presence of a lower urologic tract injury.

BACKGROUND There is controversy about the appropriate sequence of urologic investigation in patients with pelvic fracture. Use of retrograde urethrography or cystography may interfere with regular pelvic CT scanning for arterial extravasation. STUDY DESIGN We performed a retrospective study at a regional trauma center in Toronto, Canada. Included were adult blunt trauma patients with pelvic fractures and concomitant bladder or urethral disruption who underwent initial pelvic CT before operation or hospital admission. Exposure of interest was whether retrograde urethrography (RUG) and cystography were performed before pelvic CT scanning. Main outcomes measures were indeterminate or false negative initial CT examinations for pelvic arterial extravasation. RESULTS Sixty blunt trauma patients had a pelvic fracture and either a urethral or bladder rupture. Forty-nine of these patients underwent initial CT scanning. Of these 49 patients, 23 had RUG or conventional cystography performed before pelvic CT scanning; 26 had cystography after regular CT examination. Performing cystography before CT was associated with considerably more indeterminate scans (9 patients) and false negatives (2 patients) for pelvic arterial extravasation (11 of 23 versus 0 of 26, p < 0.001) compared with performing urologic investigation after CT. In the presence of pelvic arterial hemorrhage, indeterminate or false negative CT scans for arterial extravasation were associated with a trend toward longer mean times to embolization compared with positive scans (p=0.1). CONCLUSIONS Extravasating contrast from lower urologic injuries can interfere with the CT assessment for pelvic arterial extravasation, delaying angiographic embolization.

Intraoperative fluorescence angiography to determine the extent of injury after penetrating cardiac trauma.

already, the cause of the pericardial effusion was not proved. If this patient were to present with recurrent pericardial effusion despite ongoing appropriate chemotherapy for ECD, a more radical pericardial resection might be indicated because the pericardial histology was consistent with ECD. In summary, the clinical observation from this case is that ECD, although rare, has important cardiovascular presentations. Cardiac involvement might require surgical intervention. The associated systemic manifestations can complicate perioperative recovery. Successful management depends on taking the diverse clinical manifestations of this multicentric disease into account.