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Venous dialysis pressures were measured consecutively in 168 chronic hemodialysis patients for 265 patient-years of monitored dialysis. Venous dialysis pressure greater than 150 mm Hg measured by the protocol were considered elevated. Seventy-three patients had elevated venous dialysis pressures and 58 agreed to undergo elective venography (fistulogram). Fifty of 58 patients studied (86%) had significant venous stenoses. A combination of percutaneous transluminal angioplasty (PTA) and surgical revision were used to electively treat these stenoses. Early detection and treatment of these stenoses decreased fistula thrombosis and fistula replacement threefold compared with our earlier experiences. Patients with elevated venous dialysis pressure who were venogramed and treated had an occurrence of fistula thrombosis similar to patients with normal dialysis pressure (0.15 and 0.13 episodes per patient year of dialysis respectively, P = NS). In contrast patients with elevated venous dialysis pressure who refused elective fistulogram and treatment averaged 1.4 episodes of thrombosis per patient year of dialysis (P less than 0.001) compared to both other groups). We conclude that elevated venous dialysis pressure is a reliable method of detecting fistula stenoses and that the elective treatment of these stenoses significantly decreases fistula thrombosis and fistula loss.

Long-term success in xenotransplantation is currently hampered by acute vascular rejection. The inciting cause of acute vascular rejection is not yet known; however, a variety of observations suggest that the humoral immune response of the recipient against the donor may be involved in the pathogenesis of this process. Using a pig-to-baboon heterotopic cardiac transplant model, we examined the role of antibodies in the development of acute vascular rejection. After transplantation into baboons, hearts from transgenic pigs expressing human decay-accelerating factor and CD59 underwent acute vascular rejection leading to graft failure within 5 d; the histology was characterized by endothelial injury and fibrin thrombi. Hearts from the transgenic pigs transplanted into baboons whose circulating antibodies were depleted using antiimmunoglobulin columns (Therasorb, Unterschleisshein, Germany) did not undergo acute vascular rejection in five of six cases. Biopsies from the xenotransplants in Ig-depleted baboons revealed little or no IgM or IgG, and no histologic evidence of acute vascular rejection in the five cases. Complement activity in the baboons was within the normal range during the period of xenograft survival. In one case, acute vascular rejection of a xenotransplant occurred in a baboon in which the level of antidonor antibody rose after Ig depletion was discontinued. This study provides evidence that antibodies play a significant role in the pathogenesis of acute vascular rejection, and suggests that acute vascular rejection might be prevented or treated by therapies aimed at the humoral immune response to porcine antigens. (

A recently improved understanding of gut immunity has merged with current thinking in biological and medical science, pointing to an apparent function of the mammalian cecal appendix as a safe‐house for symbiotic gut microbes, preserving the flora during times of gastrointestinal infection in societies without modern medicine. This function is potentially a selective force for the evolution and maintenance of the appendix, and provides an impetus for reassessment of the evolution of the appendix. A comparative anatomical approach reveals three apparent morphotypes of the cecal appendix, as well as appendix‐like structures in some species that lack a true cecal appendix. Cladistic analyses indicate that the appendix has evolved independently at least twice (at least once in diprotodont marsupials and at least once in Euarchontoglires), shows a highly significant (P < 0.0001) phylogenetic signal in its distribution, and has been maintained in mammalian evolution for 80 million years or longer.

It is critical, both for the host and for the long-term benefit of the bacteria that colonize the gut, that bacterial overgrowth with subsequent bacterial translocation, which may lead to sepsis and death of the host, be avoided. Secretory IgA (sIgA) is known to be a key factor in this process, agglutinating bacteria and preventing their translocation in a process termed 'immune exclusion'. To determine whether human sIgA might facilitate the growth of normal enteric bacteria under some conditions, the growth of human enteric bacteria on cultured, fixed human epithelial cells was evaluated in the presence of sIgA or various other proteins. Human sIgA was found to facilitate biofilm formation by normal human gut flora and by Escherichia coli on cultured human epithelial cell surfaces under conditions in which non-adherent bacteria were repeatedly washed away. In addition, the presence of sIgA resulted in a 64% increase in adherence of E. coli to live cultured epithelial cells over a 45-min period. Mucin, another defence factor thought to play a key role in immune exclusion, was found to facilitate biofilm formation by E. coli. Our findings suggest that sIgA may contribute to biofilm formation in the gut.

Immunoglobulins regulate the complement system by activating complement on foreign surfaces and diverting reactive complement proteins away from autologous cell surfaces. Based on this model, we explored the ability of Ig to balance complement activation versus control in a pig-toprimate cardiac xenotransplantation model in which the binding of xenoreactive antibodies of the recipient to graft blood vessels and the activation of complement cause hyperacute rejection. Human IgG added to human serum caused a dose-dependent decrease in deposition of iC3b, cytotoxicity, and heparan sulfate release when the serum was incubated with porcine endothelial cells. This decrease was not caused by alteration in antibody binding or consumption of complement but presumably reflected decreased formation of C3 convertase on the endothelial cells. Infusion of purified human IgG into nonhuman primates prevented hyperacute rejection of porcine hearts transplanted into the primates. As expected, the transplants contained deposits of recipient Ig and Clq but not other complement components. The inhibition of complement on endothelial cell surfaces and in the xenotransplantation model supports the idea that IgG regulates the classical complement pathway and supports therapeutic use of that agent in humoral-mediated disease. (J. Clin. Invest. 1995Invest. .96:2404Invest. -2412

The effects of several treatments involving alpha-adrenergic mechanisms upon the early stages of rat liver regeneration were examined. Catecholamine concentrations in rat plasma were measured at various times after hepatectomy and were found to be elevated relative to those in plasma from sham-operated rats. Surgical hepatic denervation or injection of an alpha 1-adrenergic receptor antagonist (prazosin) reduced incorporation of [3H]thymidine into liver DNA during the first 24 hr after partial hepatectomy. Chronic guanethidine injections (3 to 6 weeks) reduced liver catecholamine levels, but did not affect its ability to regenerate. The inhibition of regenerative DNA synthesis by prazosin was preceded by an alteration in the binding of epidermal growth factor to regenerating liver, which was apparently the result of an increased number of epidermal growth factor receptors. Thus, alpha 1-adrenergic blockade, which affects both epidermal growth factor receptor binding and subsequent DNA synthesis in hepatocyte primary cultures, can also modulate these processes during liver regeneration in vivo.

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