THE EFFECT OF HETEROLOGOUS ANTI-LYMPHOCYTE SERUM ON LYMPHOCYTES OF THYMUS AND MARROW ORIGIN

When CY-treated mice were given sheep red blood cells the serum hemagglutinin titers produced were significantly lower than those found when mice received SRBC but not CY. Titers could be raised to the levels found in the latter group if, in addition to SRBC, the CY-treated mice received 2 x 107 normal syngeneic spleen cells or a mixture containing 1.2 x 108 normal thymus and 1.2 x 108 normal marrow cells. Inocula which contained fewer cells produced correspondingly smaller amounts of antibody. A synergistic interaction between normal thymus and marrow cells was always demonstrable in these experiments. Hemagglutinin titers produced by CY-treated mice given SRBC and 2 x 107 normal syngeneic spleen cells were always much higher than those found when the spleen cells were obtained from animals previously given ALS. Titers could be raised to normal levels if the animals in this latter group received additional injections containing mixtures of normal syngeneic thymus and marrow cells. Marrow cells alone were completely ineffective, while inocula which only contained thymus cells were much less effective than mixtures of thymus and marrow cells. These results suggest that immunosuppression by ALS is associated with the inactivation of both thymus and marrow-derived lymphocytes. In other experiments CY-treated mice received SRBC and mixtures of thymus and marrow cells from both untreated and ALS-treated donors. No decrease in the immunological competence of cells located within the thymus of ALS-treated donors was demonstrable in these experiments. Marrow cells were slightly affected but to a markedly lesser degree than were spleen cells of ALS-treated animals. In a final experiment, it was possible to show that the thymus and marrow cells of ALS-treated animals could repair the immunological defects which were present in their own spleen cell populations

IMMUNOSUPPRESSIVE AND GRAFT-REJECTING ANTIBODIES IN HETEROLOGOUS ANTI-LYMPHOCYTIC SERUM

Skin allografts survived longer on ALS-treated, complement-deficient (C5 negative) recipients than on ALS-treated, complement-competent (C5 positive) recipients. Administration of C5-positive serum to C5-negative, ALS-treated recipients resulted in reduced graft survival. A percentage of grafts from ALS-treated, C5-positive donors was rejected when transferred to untreated syngeneic recipients; this was not observed when C5-negative, syngeneic animals served as ALS-treated donors and untreated recipients. It was concluded that ALS has graft-rejecting properties which are promoted by late acting complement components. Unlike ALS-mediated graft rejection, ALS-mediated immunosuppression appeared to be independent of the late acting complement components. The effect of ALS on the humoral response to sheep erythrocytes was examined in complement-deficient and complement-competent mice. Immune-suppression was determined by ALS treatment of C5-competent and C5-deficient mice and also by transfer of in vitro ALS-treated spleen cells from C5-negative and C5-positive donors to cyclophosphamide-treated recipients. The ability of ALS to depress the humoral response to sheep cells and to decrease immunological competence of spleen cells was the same in the presence as in the absence of C5

Enteral versus parenteral nutrition in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials

Subgroup analysis comparing the effect of enteral versus parenteral nutrition on infectious complications in higher versus lower quality trials (with the median methodological score 7 as cutoff). CI confidence interval, EN enteral nutrition, M-H Mantel-Haenszel test, PN parenteral nutrition. (PDF 87 kb

Rationale and design of a proof-of-concept trial investigating the effect of uninterrupted perioperative (par)enteral nutrition on amino acid profile, cardiomyocytes structure, and cardiac perfusion and metabolism of patients undergoing coronary artery bypass grafting

<p>Abstract</p> <p>Background</p> <p>Malnutrition is very common in patients undergoing cardiac surgery. Malnutrition can change myocardial substrate utilization which can induce adverse effects on myocardial metabolism and function. We aim to investigate the hypothesis that there is a disturbed amino acids profile in the cardiac surgical patient which can be normalized by (par)enteral nutrition before, during and after surgery, subsequently improving cardiomyocyte structure, cardiac perfusion and glucose metabolism.</p> <p>Methods/Design</p> <p>This randomized controlled intervention study investigates the effect of uninterrupted perioperative (par)enteral nutrition on cardiac function in 48 patients undergoing coronary artery bypass grafting. Patients are given enteral nutrition (n = 16) or parenteral nutrition (n = 16), at least two days before, during, and two days after coronary artery bypass grafting, or are treated according to the standard guidelines (control) (n = 16). We will illustrate the effect of (par)enteral nutrition on differences in concentrations of amino acids and asymmetric dimethylarginine and in activity of dimethylarginine dimethylaminohydrolase and arginase in cardiac tissue and blood plasma. In addition, cardiomyocyte structure by histological, immuno-histochemical and ultrastructural analysis will be compared between the (par)enteral and control group. Furthermore, differences in cardiac perfusion and global left ventricular function and glucose metabolism, and their changes after coronary artery bypass grafting are evaluated by electrocardiography-gated myocardial perfusion scintigraphy and ¹⁸F-fluorodeoxy-glucose positron emission tomography respectively. Finally, fat free mass is measured before and after intervention with bioelectrical impedance spectrometry in order to evaluate nutritional status.</p> <p>Trial registration</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2183">NTR2183</a></p

The effects of long-term total parenteral nutrition on gut mucosal immunity in children with short bowel syndrome: a systematic review

BACKGROUND: Short bowel syndrome (SBS) is defined as the malabsorptive state that often follows massive resection of the small intestine. Most cases originate in the newborn period and result from congenital anomalies. It is associated with a high morbidity, is potentially lethal and often requires months, sometimes years, in the hospital and home on total parenteral nutrition (TPN). Long-term survival without parenteral nutrition depends upon establishing enteral nutrition and the process of intestinal adaptation through which the remaining small bowel gradually increases its absorptive capacity. The purpose of this article is to perform a descriptive systematic review of the published articles on the effects of TPN on the intestinal immune system investigating whether long-term TPN induces bacterial translocation, decreases secretory immunoglobulin A (S-IgA), impairs intestinal immunity, and changes mucosal architecture in children with SBS. METHODS: The databases of OVID, such as MEDLINE and CINAHL, Cochran Library, and Evidence-Based Medicine were searched for articles published from 1990 to 2001. Search terms were total parenteral nutrition, children, bacterial translocation, small bowel syndrome, short gut syndrome, intestinal immunity, gut permeability, sepsis, hyperglycemia, immunonutrition, glutamine, enteral tube feeding, and systematic reviews. The goal was to include all clinical studies conducted in children directly addressing the effects of TPN on gut immunity. RESULTS: A total of 13 studies were identified. These 13 studies included a total of 414 infants and children between the ages approximately 4 months to 17 years old, and 16 healthy adults as controls; and they varied in design and were conducted in several disciplines. The results were integrated into common themes. Five themes were identified: 1) sepsis, 2) impaired immune functions: In vitro studies, 3) mortality, 4) villous atrophy, 5) duration of dependency on TPN after bowel resection. CONCLUSION: Based on this exhaustive literature review, there is no direct evidence suggesting that TPN promotes bacterial overgrowth, impairs neutrophil functions, inhibits blood's bactericidal effect, causes villous atrophy, or causes to death in human model. The hypothesis relating negative effects of TPN on gut immunity remains attractive, but unproven. Enteral nutrition is cheaper, but no safer than TPN. Based on the current evidence, TPN seems to be safe and a life saving solution