Can prostate cancer be prevented?

The goal of primary chemoprevention is to decrease the incidence of a given cancer, simultaneously reducing both treatment-related adverse events and mortality. Prostate cancer is an attractive and appropriate target for primary prevention because of its incidence, prevalence, and disease-related mortality; its long latency and molecular pathogenesis; and epidemiologic data indicating that modifiable environmental factors may decrease risk. The Prostate Cancer Prevention Trial (PCPT) demonstrated that finasteride can prevent prostate cancer, albeit with an apparently increased risk of high-grade disease. A substantial amount of epidemiologic, molecular, and clinical evidence suggests that both selenium and vitamin E might also prevent prostate cancer, and this combination is being tested in the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Ultimately, the adoption of a preventive strategy hinges on its potential benefits weighed against the potential risks of the specific agents used.     

Can postpyelonephritic renal scarring be prevented?

Pyelonephritis in childhood may, in the worst cases, lead to long-term cardiovascular morbidity due to tubulointerstitial renal scarring. Renal damage is the end result of an interplay between (1) urinary tract anatomy and function, (2) bacterial virulence factors, and (3) the host innate immune system, which on the one hand manages bacterial clearance, but on the other causes tubulointerstitial inflammation, which underlies the renal scarring. It is unclear how common postpyelonephritic scarring is, and how many of the "scars" in fact represent congenital renal hypoplasia. We do, however, know that some situations have an increased risk for scars, i.e., large renal-uptake defects on initial renal scintigraphy or pyelonephritis in young girls with dilating vesicoureteral reflux. It seems logical that antiinflammatory or antioxidant therapy given concomitantly with antibiotics should lower the risk of postpyelonephritic scarring. Animal studies give some support to this idea, but research on humans has been surprisingly scant. In this issue of Pediatric Nephrology, we publish a study that indicates that antioxidant therapy with vitamin A or E given to children with pyelonephritis may indeed lower the risk for renal scarring. This is a track that needs to be pursued further.     

Can acute renal failure be prevented?

Correction of salt and volume depletion is paramount in the prevention of renal damage. Measures which stimulate intense filtration of glomeruli in acute renal failure, such as the use of atrial natriuretic peptide analogues, theophylline, dopamine, or growth factors should be regarded with caution, since they all increase metabolic workload in the outer medulla and hence aggravate medullary hypoxia. Neither frusemide, dopamine nor dopexamine have been shown to be better than aggressive saline loading in preventing acute renal failure in at risk patients. Until new clinical studies emerge, avoidance of nephrotoxic insults where possible, monitoring of circulating concentrations of potentially nephrotoxic drug levels and volume loading coupled with supportive measures is recommended. When volume depletion persists, usual blood pressure cannot be restored and patients remain oliguric, early referral to the intensive care unit is paramount. The mortality rate in patients with acute renal failure is high; therefore, measures which reduce the incidence and progression of renal dysfunction will be of benefit.     

Can pelvic floor injury secondary to delivery be prevented?

The number of women suffering from pelvic floor disorders (PFD) is likely to grow significantly in the coming years with a growing older population. There is an urgent need to investigate factors contributing to the development of PFD and develop preventative strategies. We have reviewed the literature and analyzed results from our own study regarding the association between delivery mode, obstetrical practice and fetal measurements, and damage to the pelvic floor. Based on our findings, we have suggested a flowchart helping the obstetrician to conduct vaginal delivery with minimal pelvic floor insult. Primiparity, instrumental delivery, large fetal head circumference, and prolonged second stage of delivery are risk factors for PFD. Pelvic floor integrity should always be seriously considered in every primiparous woman. All efforts should be aimed at minimizing any insult, which might have a significant impact on the woman’s pelvic integrity and future quality of life.     

Can pelvic floor dysfunction after vaginal birth be prevented?

Introduction and hypothesis

Significant breakthroughs in our understanding of pelvic floor dysfunction have occurred in the past two decades. The next step is to translate this understanding into effective preventative and early intervention strategies to minimize maternal morbidity from vaginal birth. We have learned enough to chart a course toward prevention.

Methods

This article outlines some major advances in understanding the pathophysiology of pelvic floor dysfunction and suggests strategies for future prevention research.

Results

Vaginal birth is the primary risk factor for the development of pelvic floor disorders and this is compounded by forceps use. Age, race, and genetics are also risk factors. Steps to prevent or minimize the development of pelvic floor problems include moderating forceps use and utilizing risk assessment tools to offer cesarean delivery to those at greatest risk.

Conclusion

These actions would represent one giant step forward in advancing the practice of obstetrics into the modern age of personalized medicine.

     

Can we stop bone loss and prevent hip fractures in the elderly?

The two main determinants of hip fractures are falls and bone loss leading to an intrinsic femoral fragility. Substantial femoral bone loss continues throughout old age, with a continuous and exponential increase in the risk of hip fracture; thus any reduction or arrest of this loss will induce an important reduction in the incidence of hip fracture. Preventive measures may be achieved during childhood by increasing peak bone mass with calcium and exercise, by using long-term estrogen replacement therapy after menopause, but also by using vitamin D and calcium supplements for late prevention in the elderly. Vitamin D insufficiency and a deficit in calcium intake are very common in the elderly living either in institutions or at home and the cumulative response to these deficits is a negative calcium balance which stimulates parathyroid hormone secretion. This senile secondary hyperparathyroidism is one of the determinants of femoral bone loss and can be reversed by calcium and vitamin D supplements. We have shown in a 3-year controlled prospective study that the daily use of supplements (1.2 g calcium and 800 IU vitamin D₃) given in a large population of 3270 elderly ambulatory women living in nursing homes reduced the number of hip fractures by 23% (intention-to-treat analysis). In parallel, serum parathyroid hormone concentrations were reduced by 28% and low baseline serum 25-hydroxy vitamin D concentration returned to normal values. After 18 months of treatment the bone density of the total proximal femoral region had increased by 2.7% in the vitamin D₃-calcium group and decreased by 4.6% in the placebo group (p<0.001). this=" prevention=" is=" safe=" and=" can=" be=" recommended=" for=" people=" living=" in=" institutions.=" it=" could=" also=" be=" useful=" in=" other=" elderly=" subjects=" at=" particular=" risk=" due=" to=" a=" low=" calcium=" intake,=" an=" absence=" of=" solar=" exposure,=" a=" low=" femoral=" bone=" density,=" a=" high=" serum=" parathyroid=" hormone=" concentration,=" a=" low=" serum=" 25-hydroxyvitamin=" d=" concentration=" and=" a=" previous=" history=" of=" falls.=" prospective=" studies=" are=" needed=" for=" further=" evaluation=" of=" these=" risk=">     

Where do T cells stand in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destruction of cartilage and bone. The destructive lesions result from both immune responses and non-antigen-specific inflammatory processes. Little is known about the primary cause of RA. Although the primacy of T-cell-related events early in the disease remains debated, strong evidence indicates that autoantigen recognition by specific T cells is crucial to the pathophysiology of rheumatoid synovitis. We will discuss evolving concepts about T-cell involvement in RA and the roles for various T cell subsets in the development of joint abnormalities. The hypothesis that RA is a T-cell driven disease was put forward when studies of RA synovium showed numerous T cells carrying activation markers. These T cells were found to participate in the complex network of cell- and mediator-driven events leading to joint destruction. Conceivably, these T cells may be stimulated by an autoantigen (whether specific to the joints or ubiquitous), a highly conserved foreign protein cross-reacting with its human homolog, or a neo-antigen expressed as a result of posttranslational events. For many years, animal models have provided valuable evidence supporting a role for T cells in RA. We will review three murine models of arthritis caused by different mechanisms. In collagen-induced arthritis, the immune response to a joint antigen is mediated by pathogenic Th1 cells that elicit severe inflammatory synovitis. Spontaneous arthritis in K/BxN T-cell-receptor transgenic mice is related to an adaptive immune response against a ubiquitous protein whose end-stage effector mechanisms are heavily dependent on the innate immune system. In the SKG model of autoimmune inflammatory arthritis, a point mutation in the gene encoding a key signal-transduction molecule in T cells causes defective T cell selection in the thymus, which releases polyclonal autoreactive T cells. Studies in these and other animal models have established that a variety of T-cell subsets whose roles vary with cell location and disease stage can contribute to synovitis. Finally, in addition to direct autoimmune attack by effector T cells, arthritis may result from defective homeostatic control of immunity by regulatory T cells.     

Can bile duct injuries be prevented? "A new technique in laparoscopic cholecystectomy"

Background  

Over the last decade, laparoscopic cholecystectomy has gained worldwide acceptance and considered to be as "gold standard" in the surgical management of symptomatic cholecystolithiasis. However, the incidence of bile duct injury in laparoscopic cholecystectomy is still two times greater compared to classic open surgery. The development of bile duct injury may result in biliary cirrhosis and increase in mortality rates. The mostly blamed causitive factor is the misidentification of the anatomy, especially by a surgeon who is at the beginning of his learning curve. Biliary tree injuries may be decreased by direct coloration of the cystic duct, ductus choledochus and even the gall bladder.