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Biomedical subjects

J W Alexander

Publications and source records attributed to J W Alexander.

At least 19 recordsLinked to original sources
PubMed1999

The effect of nutritional immunomodulation on cardiac allograft survival in rats receiving mycophenolate mofetil, cyclosporine A, and donor-specific transfusion.

BACKGROUND: Immunosuppressive drugs continue to pose significant risks such as infection, toxicity, or neoplasia when used in long-term therapy. The investigation of newer and safer combined treatment strategies that decrease the need for these drugs is becoming increasingly important. Immunonutrients are known to have significant modulating effects on the immune system. Feeding with Impact, a commercially available diet enriched with arginine, omega-3 fatty acids, and RNA, recently has been shown to extend rat cardiac allograft survival when combined with a donor-specific transfusion (DST) and cyclosporine A (CsA). Because mycophenolate mofetil (MMF) is now commonly used in the clinical setting, the current study was designed to examine the effect on rat cardiac allograft survival when MMF was added to this immunosuppressive regimen. METHODS: Intra-abdominal ACI to Lewis heterotopic cardiac allografts were performed. Study groups included untreated controls and recipients receiving varying combinations of a DST (1 mL) on the day prior to engraftment, MMF 45 mg/kg/day from the day of transplant through postoperative day six, and CsA 10 mg/kg on the day prior to operation and 2.5 mg/kg from the day of transplant through postoperative day 6. Animals were fed ad libitum with Impact diet or standard lab chow. Graft survival was determined by cessation of a palpable heartbeat. RESULTS: Treatment with MMF led to a prolonged allograft survival over historical untreated controls. The combination of MMF with a donor-specific transfusion, Impact, or CsA was associated with an increase in graft survival over MMF alone. The addition of Impact to the combination of MMF and CsA resulted in further improvement. The most pronounced graft survival advantage was seen when Impact was combined with a DST and both of the immunosuppressive agents. One quarter of the animals in this group had a palpable donor heart beat at greater than 150 days, indicating functional tolerance in those animals. CONCLUSIONS: The administration of Impact diet to treatment groups in this study was associated with graft survival advantages when compared to most of the other study groups receiving a similar drug regimen and standard chow. These findings support the importance of nutritional influences on allograft survival, and highlight the potential of diet therapy when used with short courses of clinically relevant immunosuppressive drugs.

Adjuvants, Immunologic↗
PubMed1999

Effect of pentoxifylline on survival and intestinal cytokine messenger RNA transcription in a rat model of ongoing peritoneal sepsis.

OBJECTIVE: Septic animals receiving high-protein liquid diets have increased mortality and increased production of cytokines by the gut compared with animals receiving low-protein diets. The purpose of this study was to evaluate the ability of pentoxifylline to alter gut cytokine production in a rat model of prolonged acute peritonitis, to determine its effect on survival in such animals, and to determine whether alteration of gut cytokine production was associated with survival. DESIGN: Prospective, randomized animal study. SETTING: Research laboratory. SUBJECTS: Male Lewis rats weighing between 250 and 300 g. INTERVENTIONS: Anesthetized rats had placement of a gastrostomy, followed 1 wk later by implantation of a bacteria-filled osmotic minipump into the peritoneal cavity. Rats were fed a high-protein (20% total energy) enteral diet. Saline or pentoxifylline (5 or 20 mg/kg im) was administered daily beginning at the time of pump implantation. MEASUREMENTS AND MAIN RESULTS: Septic rats fed the high-protein liquid diet and given pentoxifylline in a dose of 5 mg/kg/day demonstrated improved survival compared with saline-treated animals or animals given the high dose (20 mg/kg/day) of pentoxifylline (p< .05). Administration of pentoxifylline at 5 mg/kg/day also down regulated the production of IL-6 messenger RNA (mRNA) in liver and lipopolysaccharide binding protein mRNA in the liver and intestine of septic animals given the high-protein liquid diet. CONCLUSION: Low-dose (but not high-dose) pentoxifylline administration reduced production of some, but not all, cytokines studied in the gut and liver in a rat model of acute peritonitis and this reduced production was associated with an improved survival in such animals.

Animals↗
PubMed1999

The effect of sennosides on bacterial translocation and survival in a model of acute hemorrhagic pancreatitis.

Bacterial translocation leading to subsequent infectious complications is a significant determinant of outcome in acute hemorrhagic pancreatitis (AHP). The colonic ileus and impaired intestinal barrier function that often accompany AHP may predispose to translocation. Sennoside is a naturally occurring cathartic and choleretic agent that stimulates intestinal mucous secretion and has potent promotility effects. The impact of sennoside-induced intestinal motility and secretory function on bacterial translocation and survival was studied in a rat model of AHP. Severe acute pancreatitis was induced in rats by the intraductal infusion of 2% sodium deoxycholate (DCA, 0.4 ml/kg). A group of sham-operated rats (group A) received intraductal saline, whereas experimental animals were subsequently administered distilled water (group B) or sennoside solution (group C) by gavage every 8 h. After 48 h, intestinal transit of fluorescein isothiocyanate-labeled dextran, serum endotoxin, and amylase levels, and bacterial translocation to mesenteric lymph nodes (MLNs) and pancreatic tissue were determined. The pancreas and intestine were sampled for histologic study. All group A animals survived and did not develop pancreatitis or endotoxemia, whereas groups B and C all demonstrated severe hemorrhagic pancreatitis with evidence of necrosis. Mortality at 48 h was 55% in group B versus 12.5% in group C. Inhibition of intestinal motility was noted in 40% versus 20%, and endotoxin levels were 61.36+/-28.26 pg/L versus 5.41+/-3.58 pg/L in group B versus group C rats, respectively (p<0.001). Pancreatic tissue and MLN cultures were positive in 100% of group B survivors versus 14% of group C survivors (p<0.05). Histologic examination of the intestine in group C animals showed increased mucous secretion, proliferation of goblet cells, and evidence of rapid turnover/renewal of enterocytes. Treatment with the cathartic agent, sennoside, reduced translocation of endotoxin and bacteria, restored intestinal motility, increased mucous secretion, and reduced mortality in a model of acute hemorrhagic pancreatitis in the rat. Other cathartics may have similar properties and may be useful in preventing infectious complications in acute pancreatitis.

Acute Disease↗
PubMed1999

Nitric oxide promotes the internalization and passage of viable bacteria through cultured Caco-2 intestinal epithelial cells.

Nitric oxide (NO) may play an important role in the pathophysiology of intestinal barrier disruption. Our purpose was to investigate the effects of NO donors on the internalization and passage of bacteria through cultured intestinal epithelial cells. Human intestinal epithelial cell line Caco-2 cells were grown on microtiter plastic plates. The cells were incubated with Escherichia coli and sodium nitroprusside (SNP) or S-nitroso-N-acetyl-penicillamine (SNAP), as NO donors, at several concentrations. The numbers of viable bacteria internalized into the epithelial cells were measured. Caco-2 cells were also grown to confluency on membranes of bicameral systems. The cells were incubated with E. coli and SNP. The numbers of viable bacteria passed through the epithelial layer were determined. Viability of the bacteria and the intestinal epithelial cells after culture with SNP or SNAP were also determined. Both SNP and SNAP at .1 or 1 mmol/L increased the number of viable bacteria internalized into the enterocytes. Both 1 or 10 mmol/L SNP promoted bacterial passage through the intestinal epithelial layer. However, 10 mmol/L SNP decreased the number of viable Caco-2 cells and failed to increase the bacterial internalization into Caco-2 cells. Incubation of E. coli with SNAP at 10 mmol/L slightly decreased the number of viable bacteria and failed to increase the bacterial internalization into Caco-2 cells. We conclude that NO donors promote both the viable bacterial uptake and passage through the intestinal epithelial layer.

Bacterial Translocation↗
PubMed1999

Dietary amino acids as new and novel agents to enhance allograft survival.

Dietary supplementation with arginine was previously found to enhance cardiac allograft survival in rats when given with a donor-specific transfusion and a short low-dose course of cyclosporine. This study was performed to determine further the role of amino acid supplementation in prolonging allograft survival. Standard isocaloric, isonitrogenous diets were modified to contain 2 or 4% of energy from arginine, 2 or 4% from glutamine, 4% from glycine or the following combinations: 2% arginine with 2% glutamine, 2% arginine with 4% glutamine, or 1% arginine with 2% glutamine. These diets were started along with a donor-specific transfusion and a 7-d course of cyclosporine the day before cardiac transplantation from an ACI to Lewis strain rat. Median survival times in days for the groups were as follows: control without amino acids, 19.0; 2% arginine, 68.0; 4% arginine, 35.5; 2% glutamine, 28.5; 4% glutamine, 53.5; 4% glycine, 31.5; 2% arginine with 2% glutamine, 39.5; 2% arginine with 4% glutamine, 42.5 and 1% arginine with 2% glutamine, 35.5. Each experimental diet except 2% glutamine and 4% glycine significantly enhanced allograft survival (P < 0.05) with the 2% arginine diet being the best (91.6 +/- 32.3 d [mean +/- SEM] versus 20.1 +/- 3.2 d for control). It is concluded that both arginine and glutamine enhance the immunosuppressive effects of donor-specific transfusion and cyclosporine.

Amino Acids↗
PubMed1998

Dietary omega-3 and omega-9 fatty acids uniquely enhance allograft survival in cyclosporine-treated and donor-specific transfusion-treated rats.

BACKGROUND: Both laboratory and clinical studies have shown that dietary lipids may affect immunologic responses. This study was conducted to compare different classes of long-chain unsaturated fatty acids for their effect on allograft survival in animals receiving a donor-specific transfusion and a short course of low-dose cyclosporine (CsA). METHODS: Heterotopic ACI strain cardiac allografts were transplanted to Lewis strain rat recipients given diets with different lipid composition. In experiment 1, animals received CsA for 14 days and different diets were enriched with lipids with high concentrations of omega-3, omega-6, or omega-9 fatty acids. In experiment 2, animals received CsA for only 8 days and different diets were enriched with corn oil (omega-6), canola oil (omega-3 and omega-9), fish oil (omega-3) or a mixture of sunflower oil and fish oil (omega-3 and omega-9). RESULTS: In experiment 1, animals receiving the diet with 30% sunflower oil had the best allograft survival (200+/-42 days vs. 53+/-8 days for regular chow plus donor-specific transfusion and CsA, P<0.05). In experiment 2, diets containing canola oil (a mixture of omega-3 and omega-9 fatty acids) were associated with the best survival (P=0.0011 vs. regular chow). CONCLUSION: Dietary omega-3 and omega-9 fatty acids both enhanced cardiac allograft survival in a stringent rat strain combination. Canola oil is a convenient oil for administering both alpha-linoleic acid (omega-3) and oleic acid (omega-9) in a palatable form for human consumption. Further investigation of the potential usefulness of lipids in transplant therapy is warranted.

Animals↗
PubMed1998

Economic costs of expanded criteria donors in renal transplantation.

BACKGROUND: The organ shortage has increased interest in the use of "expanded criteria" donors (ECDs). Although much has been written concerning the clinical outcomes associated with the use of such donors, little has been published concerning the financial results associated with their use. METHODS: A retrospective cost identification study of recipients of kidneys from expanded criteria cadaveric donors was used. RESULTS: Of a total of 78 cadaveric renal transplants in fiscal year 1995, there were 38 kidneys (49%) transplanted from ECDs. Graft survival at 1 year was not statistically different between patients who received kidneys from ECDs and those who received non-ECD kidneys (84% vs. 85%, respectively). Length of stay (P < 0.05), serum creatinine at 1 year after transplantation (P < 0.01), and the percentage of patients requiring hemodialysis (P < 0.05) were all higher among patients who received kidneys from ECDs. Cold ischemic time was significantly longer in patients who received kidneys from ECDs (31.4+/-12 hr vs. 24.0+/-9 hr; P < 0.05). The total average and median costs were $12,190 and $10,911 higher in recipients of kidneys from ECDs as compared with non-ECD controls (P < 0.01). Stepwise linear regression demonstrated that length of stay was the major clinical determinant of total costs; only the use of antilymphocyte induction was otherwise significantly associated. When kidneys from ECDs were transplanted into "high-risk" recipients (age > 60 or retransplant patient), the average total costs were $15,311 more than when kidneys from ECDs were transplanted into non-high-risk patients (n=16 and 21, respectively; P < 0.05) and $20,680 more than when a non-ECD, non-high-risk pairing was undertaken (n=26; P < 0.05). CONCLUSIONS: Kidney transplantation with organs from ECDs is significantly more expensive than with organs from non-ECDs, even in the face of similar graft survival rates. Further study is needed to determine the cost-effectiveness of renal transplantation utilizing kidneys from ECDs vis-a-vis hemodialysis.

Adult↗
PubMed1998

Diets and infection: composition and consequences.

This brief review focuses on the effects of nutrient composition of enteral diets on the outcome of surgical patients and experimental models of infection. Complete enteral diets containing combinations of immunonutrients (arginine, glutamine, RNA, omega-3 fatty acids), when given postoperatively or after trauma to surgical patients, can reduce hospital stay, overall costs, and the incidence of wound complications and acquired infections. Immunonutrient diets can also reduce the length of hospital stay when given to patients admitted to the surgical intensive care unit. A high protein diet is usually required for optimal benefit, although administration of high protein immunoenhancing diets may have adverse effects in animals with severe untreated peritonitis because of a sustained overproduction of cytokines.

Animals↗
PubMed1998

Immunobiology of renal transplantation.

The clinical application of our knowledge of the immune barriers to transplantation has advanced allo-organ replacement therapy to the level of routine practice, while simultaneously engendering a critical shortage in available donors. Recent work in xenotransplantation addresses this need. The current understanding of the immune barriers to transplantation has evolved to consider alternate responses to alloantigen, namely acceptance. The delineation and application of recent discoveries in T cell costimulatory events, antigen presentation, and differential T lymphocyte responses are opening pathways towards the development of tolerogenic protocols for use in clinical transplantation. This article presents a review of transplant immunobiology with special attention to antigen presentation and T-cell activation as phases of the immune response relevant to the discussion of transplant tolerance.

Antigen Presentation↗
PubMed1998

Characteristics of long-term renal transplant survivors.

Despite the high rates of rejection, allograft failure, and patient death in the early years of renal transplantation, some patients have done remarkably well. Forty-three (17 living related donor and 26 cadaver donor recipients) such patients with an allograft that functioned for 19 years or more (range, 19 to 29 years) were followed up at this center. The patients included 24 men and 19 women, with a mean age at transplantation of 29 years, of whom 39 were white and four were black. At most recent follow-up, the mean daily dose of azathioprine was 104 mg (range, 50 to 175 mg) and that of prednisone was 10 mg (range, 5 to 20 mg). Mean serum creatinine level was 1.6 mg/dL (range, 0.7 to 5.4 mg/dL). Acute rejection occurred in 14 (33%) patients. Nine patients had one episode and five patients had two episodes of acute rejection. Long-term risks to the recipients appeared in the form of coronary artery disease in 10 (23%) patients; malignancy in 13 (30%) patients, which included nine patients with skin malignancy; and chronic hepatitis C virus (HCV) infection in four patients, two of whom died of complications of liver failure. Other complications included avascular bone necrosis in five patients, which required total hip replacement in two patients; hyperlipidemia requiring treatment in 16 (37%) patients; posttransplantation diabetes mellitus in 10 (23%) patients after a median of 17.5 years (range, 1 to 23 years); and hypertension in 23 (53%) patients. There were seven deaths (three of coronary artery disease, two of liver failure, one each of sepsis and malignancy) and eight graft losses (five to death with function, two to chronic rejection, and one to focal and segmental glomerulosclerosis). Although long-term allograft success results in patients receiving minimal amounts of immunosuppression and having good renal function, long-term renal transplant survivors are at risk for significant morbidity even in the third decade posttransplantation.

Adolescent↗
PubMed1998

The detection of microbial DNA in the blood: a sensitive method for diagnosing bacteremia and/or bacterial translocation in surgical patients.

OBJECTIVE: The purpose was to determine the sensitivity of detecting microbial DNA in the blood of surgical patients as a measure for diagnosing systemic infection and/or translocation from the gut. SUMMARY BACKGROUND DATA: Microbial infections and translocation of intestinal bacteria are thought to contribute to multiple system organ failure, but bacterial cultures are often negative in patients with this complication. METHODS: DNA was extracted from the blood of 40 surgical patients and 20 healthy controls. Polymerase chain reaction (PCR) techniques were used to amplify genes from Escherichia coli, Bacteroides fragilis, and a region of 16S ribosomal RNA found in many gram-positive and -negative bacteria. RESULTS: Bacterial DNA genes were not detected in healthy volunteers but were found in all patients with positive blood cultures. All eight transplant patients receiving OKT3 therapy had microbial DNA in their blood, possibly indicating translocation from the gut. Sixty-four percent of critically ill patients had microbial DNA detected in their blood, but only 3 (14%) had positive blood cultures. CONCLUSIONS: The PCR method is more sensitive than blood cultures for detecting bacterial components in the blood of critically ill surgical patients and may detect microbial translocation from the intestine.

Adolescent↗
PubMed1998

The relationship of job satisfaction with organizational variables in public health nursing.

OBJECTIVE: This study examined the relationship of the organizational variables of structure, technology, and environment with job satisfaction among public health nurses in a southeastern state. BACKGROUND: There is little research on the characteristics of the work environment that influence nurses to remain in the public health work setting. Prior research in this setting has focused on the negative aspects of the nursing positions. These aspects of least desirability for the public health nurse provide only a partial view of job satisfaction. To decide and plan specific strategies, the nurse administrator must have valid and useful information about the positive aspects of job satisfaction of public health nurses. METHODS: The researchers distributed a questionnaire to all licensed nursing personnel employed by a state public health department. Data collection consisted of four tools: 1) structure instrument; 2) technology instrument; 3) environmental uncertainty instrument; and 4) McCloskey-Mueller Job Satisfaction Scale (MMSS). The sample of 838 public health nurses (response rate of 50.6%) included representation from all 13 districts and the central office of the public health department. RESULTS: Significant relationships were found between job satisfaction and the demographic variables of nurse category (registered nurse and licensed practical nurse) and years of experience with the public health department. The critical variable for predicting job satisfaction in this group of public health nurses was organizational structure (vertical participation, horizontal participation, and formalization). Dimensions of structure accounted for 41% of the variance in job satisfaction. Structure remained the critical predictor of job satisfaction, although the findings do not suggest a conclusive model. The three dimensions of technology (instability, variability, and uncertainty) and environmental uncertainty assumed significance only in concert with each other or with the dimensions of structure. CONCLUSIONS: This study contributes to nursing management theory by examining the relationship of organizational structure, technology, and environmental uncertainty with job satisfaction in public health nurses. This research also has implications for nurse administrators in public health for creating more flexible work environments and facilitating staff involvement in decision making.

Education, Nursing↗