Repair of spinal cord injuries: where are we,where are we going?

Repairing the spinal cord has for a long time been a 'holy grail' for neuroscientists. No achievement in neuroscience is more difficult to achieve, and none would have the same impact amongst the medical profession and the public. Yet no patient has yet benefited from a regeneration therapy. At last sufficient progress has been made in the basic science of axon regeneration that treatments that would partially repair a spinal injury are imminent. A full repair of spinal injury still remains elusive. This review summarises progress to date, and suggests ways in which progress towards treatment of spinal injury patients might be made.     

Laparoendoscopic single-site surgery in urology: where have we been and where are we heading?

One-port, single-incision laparoscopy is part of the natural development of minimally invasive surgery. Refinement and modification of laparoscopic instrumentation has resulted in a substantial increase in the use of laparoendoscopic single-site surgery (LESS) in urology over the past 2 years. Since the initial report of single-port nephrectomy in 2007, urologists have successfully performed various procedures with LESS, including partial nephrectomy, pyeloplasty, orchiectomy, orchiopexy, ureterolithotomy, sacrocolpopexy, renal biopsy, renal cryotherapy, and adrenalectomy. Further advancements in technology, such as magnetic anchoring and guidance systems, and robotic instrumentation, may allow broader application of this emerging surgical technique. Future research is required to determine the intraoperative and postoperative benefits of LESS in comparison with standard laparoscopy.     

Xenotransplantation: where are we in 2008?

Xenotransplantation holds promise to solve the ever increasing shortage of donor organs for allotransplantation. In the last 2 decades, major progress has been made in understanding the immunobiology of pig-into-(non)human primate transplantation and today we are on the threshold of the first clinical trials. Hyperacute rejection, which is mediated by pre-existing anti-alpha Gal xenoreactive antibodies, can in non-human primates be overcome by complement- and/or antibody-modifying interventions. A major step forward was the development of genetically engineered pigs, either transgenic for human complement regulatory proteins or deficient in the alpha1,3-galactosyltranferase enzyme. However, several other immunologic and nonimmunologic hurdles remain. Acute vascular xenograft rejection is mediated by humoral and cellular mechanisms. Elicited xenoreactive antibodies play a key role. In addition to providing B cell help, xenoreactive T cells may directly contribute to xenograft rejection. Long-term survival of porcine kidney- and heart xenografts in non-human primates has been obtained but required severe T and B cell immunosuppression. Induction of xenotolerance, e.g. through mixed hematopoietic chimerism, may represent the preferred approach, but although proof of principle has been delivered in rodents, induction of pig-to-non-human primate chimerism remains problematic. Finally, it is now clear that innate immune cells, in particular macrophages and natural killer cells, can mediate xenograft destruction, the determinants of which are being elucidated. Chronic xenograft rejection is not well understood, but recent studies indicate that non-immunological problems, such as incompatibilities between human procoagulant and pig anticoagulant components may play an important role. Here, we give a comprehensive overview of the currently known obstacles to xenografting: immune and non-immune problems are discussed, as well as the possible strategies that are under development to overcome these hurdles.     

Stone composition: where do we stand?

Kidney stones are a common disorder of the urinary tract. Nephrolithiasis is a morbid and expensive disease. The prevalence and incidence are estimated at 5-10% and 100-300/100,000/year, respectively. Relapses occur in 50-70% of all cases. For these reasons, prevention of stone formation is of great importance. Knowing the composition of the calculus is thus fundamental for a more complete evaluation of the metabolic study. The nature of the calculus in fact helps the physician to find a convenient metaphylaxis consisting of both sanitary and therapeutic measures. Study of the composition of urinary stones remains one of the most interesting aspects of the lithiasic pathology today. Presently crystallographic examination constitutes one of the most precise and less expensive methodologies to identify the nature of the concretion. This method also allows the urologist to catalogue the typology of the lithiasis during endoscopy.     

Ischemic nephropathy: where are we now?

Identification and reversing the loss of kidney function beyond occlusive disease of the renal arteries poses a major clinical challenge. Recent studies indicate that atherosclerotic renal artery stenosis develops as a function of age and is commonly associated with other microvascular disease, including nephrosclerosis and diabetic nephropathy. The risks of renal artery stenosis are related both to declining kidney function and to accelerated cardiovascular disease, with increased morbidity and mortality. Newer drugs, including agents that block the renin-angiotensin system, have improved the level of BP control for renovascular hypertension. Progressive renovascular disease during medical therapy can produce refractory hypertension, congestive heart failure, and renal failure with tubulointerstitial fibrosis. Recent studies indicate a complex interplay of oxidative stress, endothelial dysfunction, and activation of fibrogenic cytokines as a result of experimental atherosclerosis and renal hypoperfusion. Advances in imaging and interventional devices offer major new opportunities to prevent progressive loss of kidney function. Recent series indicate that although 25 to 30% of patients with impaired renal function can recover glomerular filtration after revascularization, many have no apparent change in kidney function and 19 to 25% experience a significant loss of kidney function, in some cases as a result of atheroemboli. To select patients who are most likely to benefit from vascular intervention, clinicians should understand the pathophysiology of developing ischemic nephropathy and the potential hazards of revascularization in the setting of diffuse atherosclerotic disease. Further research should be directed toward identification of critical disease, regulation of fibrogenesis, and the interaction with other atherosclerotic processes.