Xenotransplantation: is this the future?

The modern era of xenotransplantation, ie, transplantation across species, involving use of genetically modified pigs as potential organ and tissue donors for human recipients, is now more than 5 years old but remains essentially an experimental and controversial procedure. The status of the field is reviewed with regard to immunologic barriers, especially delayed xenograft rejection, infectious risks, biocompatibility issues, and associated problems. The case is made that robust clinical application is still at least a decade away although in the interim knowledge developing from the experimental approaches under investigation is proving of unexpected use in several areas of medicine.     

Ouabain-like factor: is this the natriuretic hormone?

This review focuses on the most recent data published in the field of the sodium-potassium pump inhibitors regarding the hypothetical structure, the secretory stimuli and the pathophysiological implications for particular diseases, such as hypertension. On the basis of the findings published so far, we reconsider and discuss the 'natriuretic hypothesis' for explaining the role of the endogenous sodium-potassium ATPase inhibitor. We propose the ouabain-like factor as a modulator of the renal sodium-potassium pump, that can be considered as a new pharmacological target for hypertension therapy.     

Gremlins: is this what renal fibrogenesis has come to?

Gremlin is a member of the differential screening-selected gene aberrative in the neuroblastoma (DAN) family of bone morphogenetic protein (BMP) antagonists. Gremlin influences diverse processes in growth, differentiation and development. Increased expression of gremlin has recently been demonstrated in several models of diabetic nephropathy. Gremlin arrests the cell cycle in mesangial cells and has also been shown to be upregulated in transdifferentiated renal proximal tubular cells. This review summarizes emerging evidence implicating gremlin in the pathophysiology of glomerulosclerosis and tubulointerstitial fibrosis. Gremlin is a potential novel therapeutic target in progressive renal diseases.     

When is the risk acceptable to proceed to noncardiac surgery following an acute myocardial infarction?

There is a large degree of uncertainty regarding the optimal time delay between an acute (≤ 7 days) or recent (8-30 days) myocardial infarction and a patient undergoing scheduled, noncardiac surgery. Historically, the re-infarction rate for patients undergoing non-cardiac surgery within three months of a myocardial infarction has been 5%, with a very high associated mortality rate. The American Heart Association has suggested that non-cardiac surgery is acceptable six weeks after a myocardial infarction. This review considers the pathophysiology of resolution, the therapeutic responses to acute myocardial infarctions and the predictors of outcome, which may assist with the risk-benefit analysis concerning an appropriate time to proceed with non-cardiac surgery following an acute myocardial infarction. These predictors include the presence of cardiac failure, as evaluated clinically by cardiac echocardiography and increases in B-type natriuretic proteins, and the presence of persistent ischemia, as evaluated by elevations in troponin levels and ST-segment depression.     

General anesthetic-induced neurotoxicity: an emerging problem for the young and old?

PURPOSE OF REVIEW: A growing body of evidence from cells, rodents, and sub-human primates suggests that general anesthetics can be neurotoxic to the developing and senescent brain. We review this evidence and put the studies into perspective for the practicing clinician. RECENT FINDINGS: Studies indicate that a variety of general anesthetics, which act primarily as gamma-amino-butyric acid receptor modulators and N-methyl-D-aspartic acid glutamate receptor antagonists, produce apoptotic neurodegeneration in the developing rodent and nonhuman primate brain. Vulnerability to this neurotoxicity is greatest during the period of synaptogenesis and presumably reflects disruption of the normal balance between excitation and inhibition during a critical period of brain development. Moreover, in the rodent, the neurodegeneration is associated with cognitive impairment into adulthood. Recent data also reveal that general anesthesia produces enduring cognitive impairment in aged but not young rodents and that halothane and isoflurane increase the generation and toxicity of amyloid beta, a protein strongly implicated in the pathogenesis of Alzheimer's disease. The meaning of these experimental results for human surgical patients is unclear, however, because human studies are lacking. SUMMARY: General anesthetics produce neurotoxicity and enduring cognitive impairment in young and aged animals but it is premature to change clinical practice because the issue has not been adequately studied in humans.     

Obliterative bronchiolitis following lung transplantation: from old to new concepts?

Lung transplantation has come of age and is now considered a valid treatment for selected patients with end-stage lung disease. In recent years, survival rates have much improved, although the development of chronic rejection, characterized by a progressive and irreversible decline in FEV₁, which is clinically defined as bronchiolitis obliterans syndrome (BOS) remains the major obstacle to long-term survival. Extensive research efforts with special emphasis on innate immunity have recently led to new insights with the identification of at least two different phenotypes: on the one hand there is an azithromycin-responsive phenotype (the so-called neutrophilic reversible allograft/airways dysfunction (NRAD), on the other hand there is an azithromycin-unresponsive phenotype (the fibroproliferative form of BOS or classical obliterative bronchiolitis). The present review intends to give the scientific evidence for these two subtypes, and to clarify the role of azithromycin in the treatment of BOS.     

Must the old and young compete for health care resources?

The number of older persons in our society is increasing as the number of younger persons decreases. Expenditures on the young are decreasing and those on the elderly are increasing. Questions relating to the decisions that may be made in the process of allocation of resources for these competing groups are examined in detail. The goal of meeting all individual needs may well require setting "reasonable" limits and fashioning a broader societal perspective.     

Lumboperitoneal shunts: are the complications acceptable?

Summary Background. Lumboperitoneal shunts have long been used in the treatment of benign intracranial hypertension, postoperative pseudomeningocele, CSF leak and communicating hydrocephalus. Although they can provide a rapid and effective resolution of the symptoms there are major disadvantages associated with their use.Method. We retrospectively analyzed the records of 21 patients who underwent LP shunt insertion in our institution during the study period.Findings. Eighteen patients (85.7%) underwent at least one shunt revision with a total of 63 revisions. Shunt related infections were observed in 7 cases and 7 patients developed Chiari malformation, 2 (9%) of these requiring further treatment.Conclusions. Despite the symptomatic control achieved with lumboperitoneal shunts we find the complication and revision rates unacceptably high. The technique should be re-evaluated and other treatment strategies considered.     

Sorting the hype from the facts in testicular cancer: is testicular cancer related to trauma?

PURPOSE: The rate of testicular cancer is increasing. Trauma severe enough to cause testicular atrophy is a putative risk factor for testicular cancer but the epidemiological evidence is not conclusive. A population based, multicenter case-control study was performed from 1995 to 1997 to investigate potential risk factors for gonadal and extragonadal germ cell cancer. MATERIALS AND METHODS: The study was done in 5 German regions. Interviews were performed with 269 eligible male patients with a histologically verified diagnosis and 797 controls. Detailed information on medical and family history was collected at personal interviews. RESULTS: We identified a significantly elevated risk for testicular cancer in relation to testis and/or groin trauma (odds ratio 2.5, 95% confidence interval [CI] 1.51 to 4.20). After introducing a lag time by excluding reports of trauma within the last 12 months before diagnosis or interview the corresponding odds ratio was 2.1 (95% CI 1.24 to 3.61). Analysis of the circumstances and the reported types of injury allowed us to restrict the study to testis trauma specifically, which had an odds ratio of 3.49 (95% CI 1.78 to 6.81). To account for a potential reporting bias analysis was restricted to traumatic episodes for which medical attention was sought. This restriction resulted in an odds ratio of 0.70 (95% CI 0.19 to 2.63) after excluding from study trauma reports within the last 12 months. CONCLUSIONS: The results of our study do not support the hypothesis that testicular trauma is an important risk factor for testicular cancer. The possibility of recall bias should be considered.