Is there a survival advantage in Asian peritoneal dialysis patients?

Over the last decade, epidemiological surveys and qualitative research literature have demonstrated and validated a better survival in the Asian peritoneal dialysis population. This review summarizes the current understanding of Asian peritoneal dialysis patient survival and attempts to scrutinize the supposed survival advantage of this population group. We outlined the published peritoneal dialysis survival data from a literature search, with reference to dialysis patient cohorts from 1983 through 2002 for prevalent cases and 1980 through 2002 for incident patients. Two-year and 5-year patient survival rates in excess of 80% and 60% respectively were demonstrated in Asian countries, which compared favorably with the CANUSA, ADEMEX and most Caucasian series. Better end-stage renal disease patient survival is apparent despite a dialysis adequacy disadvantage, for reasons yet to be identified. As is the case of other racial disparities in medical care, such a difference is a product of more than biological differences and include budgetary barrier, health care system and geographic variation, physician bias and statistical pitfalls. Particular efforts should therefore be made to explore the underlying reason(s) for the Asian peritoneal dialysis patient survival advantage. Alternative approach and guidelines to peritoneal dialysis delivery in Asia might be warranted.     

Hypersociability in Williams syndrome: a role for the amygdala?

We read with great interest the paper of Riby et al. regarding atypical, unfamiliar face processing in Williams syndrome (WS; Riby, Doherty-Sneddon, & Bruce, 2008a). It offers considerable insight into the mechanism of facial perception in humans and a further elaboration of the hypersociability observed in patients with Williams syndrome. We would like to suggest that the neurologic mechanisms underlying the hypersociability in WS may be attributable to an impaired recognition of facial expressions of threat, a feature that localises to the amygdala.     

Management of intracranial hemorrhage in patients with mechanical circulatory support: a role for low-molecular-weight heparins?

Patients on mechanical circulatory support are at high risk of bleeding, particularly intracranial hemorrhage (ICH). The management of ICH in patients needing anticoagulation and antiplatelet therapies remains a challenge. We report our initial experience of ICH management with low-molecular-weight heparin in patients with mechanical circulatory support, without bleeding or thromboembolic complications.     

Knee osteoarthritis: a role for bradykinin?

Osteoarthritis (OA) is a painful and degenerating progressive disease of the joints which affects millions of patients worldwide. The cause of OA is largely unknown. Among the potential therapies for the symptomatic treatment of OA, the intra-articular administration of a specific bradykinin (BK) B(2) receptor antagonist has been reported to produce a long lasting analgesic effect in patients affected by knee OA. BK is a vasodilator and inflammatory nonapeptide which is generated in OA synovium. It contributes to the initiation and maintenance of inflammation, to exciting and sensitizing sensory nerve fibres, thus producing pain, and to activating synoviocytes and chondrocytes which are the main cells involved in the homeostasis of synovial fluid and cartilage, respectively. Moreover, BK synergistically potentiates the effects produced by pro-inflammatory cytokines. Biochemical and preclinical evidence supporting the therapeutic relevance of B(2) receptor blockade in OA pathophysiology are reviewed in this publication.     

Haemorrhaging lesion in the breast: is there a role for embolisation?

Angiosarcoma of the breast is an extremely rare condition. This case illustrates the use of embolisation as a modality of treatment for primary breast angiosarcoma. No other case has been reported on the use of embolisation for this disorder.     

Ontogeny of spatial navigation in rats: a role for response requirements?

Three experiments investigated the role of response requirements in the Morris water maze for pre- and postweanling rats. Fischer-344N pups were required to locate a hidden platform using extramaze cues in a tank modified for the pups' immature response repertoire. Weanlings (20-22 days) displayed spatial learning in a pool 1/2 the size of the adults' (Experiment 1); by 26-28 days of age, probe performance was comparable to adults' on quadrant preference and platform-crossing measures. Preweanlings (17 days), in a pool 1/3 the original size, significantly reduced escape latencies and displayed quadrant preference and platform-crossing scores indicative of spatial navigation. These results suggest that despite its protracted postnatal development, the preweanling hippocampus allows neural integration of visual-spatial information; however, the capacity to demonstrate such learning is dependent on task parameters and the pup's response repertoire.     

ANCA-associated vasculitis: is there a role for neutrophil apoptosis in autoimmunity?

The primary small vessel systemic vasculitides are disorders that target small blood vessels, inducing vessel wall inflammation, and are associated with the development of antineutrophil cytoplasmic antibodies. Multiple organs are attacked including the lungs and kidneys. Increasing knowledge of pathogenesis suggests that the antibodies activate neutrophils inappropriately, leading to endothelial and vascular damage. Cytokines, such as tumor necrosis factor, can facilitate damage by priming neutrophils and activating endothelial cells. Apoptosis of infiltrating neutrophils is also disrupted by antineutrophil cytoplasmic antibody activation. Removal of these effete cells occurs in a proinflammatory manner, promoting persistent inflammation. The autoimmune response may be promoted by aberrant phagocytosis of apoptotic neutrophils by dendritic cells. Understanding pathogenesis can help to rationalize existing therapies and indicate new approaches to therapy.     

Are enterococci playing a role in postoperative peritonitis in critically ill patients?

This prospective non-interventional study is aimed at evaluating the role of enterococci in the postoperative course of postoperative peritonitis (POP) and the predictive factors for isolating Enterococcus spp. All adult patients, hospitalized in intensive care, who had POP between September 2006 and February 2010 were analysed. The patients' baseline clinical characteristics and microbiological and surgical characteristics of the first episode of POP were recorded. The rates of surgical and non-surgical complications and mortality were studied. A total of 139 patients were analysed and Enterococcus spp. were recovered in 61 patients (43%). The presence of enterococci was associated with significantly more intra-abdominal abscesses (26% vs 12%, p=0.025), but did not affect the rate of reoperation or mortality. Antibiotic use before reoperation was the only independent predictive factor for isolating enterococci (OR=2.19, CI95%: 1.02-4.70, p<0.043). Although mortality was not affected by the presence of Enterococcus spp., a higher rate of intra-abdominal abscess was found, suggesting that enterococci play a significant role in postoperative peritonitis, but the need to treat them remains to be determined. Previous antibiotic use before reoperation was a key factor in predicting the subsequent recovery of enterococci.     

Atherosclerosis in HIV patients: a new face for an old disease?

As we have become more familiar with the pathogenesis of atheroma, it has become recognized atherogenesis is mainly an inflammatory disease. Therefore, it is not surprising that a body of evidence demonstrates that endothelium injury is associated with the progression and severity of HIV infection. Another important question is: do antiretroviral drugs increase or reduce endothelial injury? Various studies support the hypothesis that HAART does induce activation of endothelial function. Thus, HIV virus as well as immune reconstitution and HAART itself promote premature endothelial activation. Such a prominent role played by inflammatory events could affect the structure of the arterial lesions in HIV patients that could present different characteristics with respect to the classical atheroma. In fact, in two HIV patients with severe stenosis of the carotid, histology revealed extensive inflammatory infiltration of the vascular wall. The characteristics of these lesions were similar to those of arteritis. Another study evidenced that the ultrasonographic structure of the lesions in HIV patients substantially differ from those found in atherosclerosis, sharing similar characteristics with arteritis. We hypothesize that the atherosclerotic lesions in HIV patients develop in two distinct phases: the first one characterized by an inflammation of the vascular wall, and subsequently, the lesions could evolve towards the classic feature of the atheroma. The lesions in the first phase are probably determined by immunodeficiency, immune reconstitution, and the same effect of HAART. In the second phase they could be maintained by the classic risk factors.     

Impaired B lymphopoiesis in old age: a role for inflammatory B cells?

Continued generation of new B cells within the bone marrow is required throughout life. However, in old age, B lymphopoiesis is inhibited at multiple developmental stages from hematopoietic stem cells through the late stages of new B cell generation. While changes in B cell precursor subsets, as well as alterations in the supporting bone marrow microenvironment, in old age have been known for the last 20 years, only more recently have insights into the cellular and molecular mechanisms responsible become clarified. Our recent discovery that B cells in aged mice are pro-inflammatory and can diminish B cell generation within the bone marrow suggests a potential mechanism of inappropriate “B cell feedback” which contributes to a bone marrow microenvironment unfavorable to B lymphopoiesis. We hypothesize that the consequences of a pro-inflammatory microenvironment in old age are (1) reduced B cell generation and (2) alteration in the “read-out” of the antibody repertoire. Both of these likely ensue from reduced expression of the surrogate light chain (λ5 + VpreB) and consequently reduced expression of the pre-B cell receptor (preBCR), critical to pre-B cell expansion and Vh selection. In old age, B cell development may progressively be diverted into a preBCR-compromised pathway. These abnormalities in B lymphopoiesis likely contribute to the poor humoral immunity seen in old age.

     

Ischemic preconditioning: a potential role for protein S-thiolation?

Oxidant stress plays a crucial role in the triggering of cardioprotection involving ischemic preconditioning (IPC). We have used biotin-tagged cysteine to probe for redox-modified proteins in IPC protocols. Cysteine was biotinylated and introduced into isolated rat hearts. S-Thiolated proteins were detected and quantified using nonreducing western blots probed with streptavidin-horseradish peroxidase. Controls (15 min of aerobic perfusion plus 5 min of 0.5 mM biotin-cysteine plus 5 min of aerobic perfusion) showed low-level protein S-thiolation. Hearts preconditioned with 5 min of ischemia and reperfused for 5 min with biotin-cysteine plus 5 min of aerobic perfusion showed increased thiolation (160%) that was fully blocked by the antioxidant mercaptopropionylglycine, which is also known to block IPC. "Preconditioning" agonists (phorbol 12-myristate 13-acetate or phenylephrine) or oxidants (hydrogen peroxide or diamide) administered during aerobic preparations to biotin-cysteine-loaded hearts induced efficient protein S-thiolation. Preconditioning agonist-induced S-thiolation was significantly attenuated by diphenyleneiodonium (a flavoprotein inhibitor) or by the protein kinase C inhibitor bisindolylmaleimide I. Additional studies testing the role of a Nox2-containing NAD(P)H oxidase as the source of the oxidant stress essential to the triggering IPC showed that protein S-thiolation was the same in wild-type and Nox2 knockout mice.     

Is there a role for viruses in triggering autoimmune hepatitis?

A role for viruses in autoimmune hepatitis (AH) has been repeatedly proposed but convincing evidence links only two viruses, hepatitis A and Epstein-Barr virus, to the type 1 form of the disease, and only in those rare cases where a genetic predisposition exists and the viral infection occurs at the right time, i.e. when other unknown factors are cooperating. In spite of an impressive amount of information conclusively showing molecular mimicry between cytochrome P450IID6 (the target autoantigen of autoantibodies characteristic of AH type 2) sequences and viral (hepatitis C virus, herpes simplex virus 1, cytomegalovirus, human T lymphotropic viruses 1 and 2) or bacterial (Salmonella typhimurium) antigens, no infectious agent is clearly able to induce this second form of the disease. In conclusion, the molecular mimicry theory has so far found little clinical evidence in its support and many more clinical observations are needed in order to unreveal possible links between viruses and AH.     

Tolerance in mixed chimerism – a role for regulatory cells?

The establishment of mixed hematopoietic chimerism induces life-long donor-specific organ graft tolerance while obviating the need for chronic immunosuppression. Recent advances have dramatically reduced the conditioning toxicity required to achieve mixed chimerism. We argue that the achievement of high levels of donor chimerism ensures life-long deletion of donor-reactive T cells, precluding and obviating the need for regulatory mechanisms in the maintenance of tolerance. However, in situations where high levels of donor chimerism cannot be established or sustained, control of immune responsiveness can be achieved through additional mechanisms, including regulatory T cells.