Biomedical subjects

R Gennari

Publications and source records attributed to R Gennari.

At least 37 records · Page 2Linked to original sources

PubMed1996

Effects of the angiotensin converting enzyme inhibitor enalapril on bacterial translocation after thermal injury and bacterial challenge.

Burn injury and sepsis produce acute gastrointestinal derangements that may predispose patients to bacterial translocation. We studied the effects of enalapril, an angiotensin converting enzyme inhibitor (ACEI), on gastrointestinal anatomic alterations, bacterial translocation, and related mortality during gut-derived sepsis in burned mice that had received a prior bacterial challenge. BALB/c mice (n = 111) were treated with enalapril 10 or 1 mg/kg body weight or sterile saline as control twice daily for 3 days. They were then gavaged with 10(a)111 in radiolabeled or unlabeled Escherichia coli and given a 20% total body surface area (TBSA) burn injury. Animals gavaged with unlabeled bacteria were observed for survival (n = 60). Survival was significantly higher in the group receiving enalapril 10 mg/Kg compared with control (75% vs. 10%). Mice treated with enalapril maintained small intestine weight, measured 4 h postburn, and ileal mucosal height was preserved, whereas burned untreated animals lost intestinal weight and mucosal height. Bacterial translocation was decreased in mice treated with enalapril, but killing was unaffected. This study suggests that treatment with enalapril positively affects the outcome in gut-derived sepsis by ameliorating gastrointestinal structural and functional damage and decreasing bacterial translocation.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1995

Anti-interleukin-6 antibody treatment improves survival during gut-derived sepsis in a time-dependent manner by enhancing host defense.

OBJECTIVE: To determine the in vivo neutralizing activities of anti-interleukin-6 (IL-6) antibody on survival rate and host defense in a clinically relevant model of infection. DESIGN: Prospective, randomized, experimental animal study. SETTING: University and Shriners Burns Institute research laboratories. SUBJECTS: Two hundred seventy-six adult, female Balb/c mice. INTERVENTIONS: Balb/c mice were treated with 10 micrograms of antimurine IL-6 antibody, nonspecific murine immunoglobulin G (IgG), or placebo at 2, 4, or 8 hrs after they underwent bacterial challenge by gavage of 10(10) Escherichia coli and thermal injury. The survival rate was determined. The number of viable translocated bacteria, the total amount of translocation, and the percentage of bacteria that survived were also studied in different tissues. MEASUREMENTS AND MAIN RESULTS: Survival rate after burn and gavage was significantly improved in animals treated with antimurine IL-6 antibody at 2 and 4 hrs but not at 8 hrs after injury compared with control animals treated with nonspecific IgG or saline. The IL-6 serum concentration was significantly lower after burn and gavage in the animals treated 2 and 4 hrs after injury compared with nontreated animals. Better killing of translocated bacteria was observed in the tissues of animals treated with antimurine IL-6 antibody 2 hrs after injury. CONCLUSIONS: Treatment with antimurine IL-6 antibody at 2 and 4 hrs after injury, but not at 8 hrs after injury, positively affects outcome during gut-derived sepsis. Moreover, the beneficial effect of treatment after 2 hrs was related to an enhanced clearance of translocated bacteria.

Animals↗

PubMed1995

Alterations in lymphocyte subsets as prognosticators of postoperative infections.

OBJECTIVE: To evaluate changes in lymphocyte subsets after major abdominal and thoracic operations, and to correlate changes with the development of clinically relevant infections postoperatively. DESIGN: Open study. SETTING: University hospital, Italy. SUBJECTS: 33 patients who were to undergo major abdominal or thoracic operations. INTERVENTIONS: Lymphocyte subsets were measured by cytofluorimetry before operation and 1, 3, 5, and 7 days postoperatively. MAIN OUTCOME MEASURES: Correlation between changes in the number of lymphocyte subsets and development of infection. RESULTS: Lymphocyte subsets were within the reference range in all patients before operation. 10/33 Patients developed infections (pneumonia, bacteraemia, or wound or urinary tract infections) between the second and the ninth days postoperatively (30%). On day 1 the numbers of all lymphocyte subsets had decreased significantly compared with the preoperative measurements in all patients (CD3 p < 0.01, CD4 p < 0.001, and CD8 p < 0.05). The reduction in CD3 was significantly greater in the group that developed infections (p < 0.001). Among patients who did not develop infections the numbers of lymphocyte subsets had returned to the reference range within a week of operation whereas among patients who developed infections they remained depressed (p < 0.05). CONCLUSION: The synchronous reduction in numbers of all lymphocyte subsets on the first day postoperatively to below 50% of the reference range (CD3 to < 600/microliters, CD4 to < 400/microliters, and CD8 to < 250/microliters) predicted the development of infection postoperatively with an accuracy of 89%, a sensitivity of 80%, and a specificity of 96%.

Adult↗

PubMed1995

Effect of different regimens of gut decontamination on bacterial translocation and mortality in experimental acute pancreatitis.

OBJECTIVE: To assess the effect of four regimens of antibiotics (compared with a control regimen of distilled water) given orally on gut decontamination, bacterial translocation, and mortality in acute necrotising pancreatitis in mice. DESIGN: Randomised experimental study. SETTING: University hospitals, USA and Italy. MATERIALS: 150 young Swiss Webster mice. INTERVENTION: All mice were fed a diet deficient in choline and supplemented with ethionine. They were then randomised to be given by gavage (36 hours after starting the diet): distilled water (controls, group 1); aztreonam along (group 2); neomycin, erythromycin, metronidazole (group 3); polymyxin B and amikacin (group 4); polymyxin B, amikacin, amphotericin B (group 5). 20 Mice in each group were treated for 10 days, and the remaining 10 in each group were killed after 3 days. MAIN OUTCOME MEASURES: Survival, and qualitative and quantitative cultures of the liver, lungs, pancreas and caecum. RESULTS: The best survival rate during the first 7 days was in group 5, but by day 10 there was no difference among the groups. All the antibiotic regimens reduced the number of bacteria in the caecum and all but aztreonam alone (group 2) reduced the rate of translocation of both Gram negative and Gram positive bacteria to all organs studied. Translocation of yeast occurred in those animals in groups 2, 3, and 4 in which there was overgrowth of fungi in the caecum. CONCLUSION: Gram negative and Gram positive organisms and fungi may have an important role in infective morbidity and mortality in acute pancreatitis, and selective decontamination with polymyxin B, amikacin, amphotericin B reduced the incidence of translocation related infections and early mortality in mice with acute necrotising pancreatitis.

Acute Disease↗

PubMed1994

Effects of antimurine interleukin-6 on bacterial translocation during gut-derived sepsis.

BACKGROUND: Recent studies have shown that interleukin-6 (IL-6) is involved in the systemic changes that are associated with infection and tissue injury and that there is a correlation between high levels of IL-6 and poor outcome during several pathologic conditions. OBJECTIVE: The effects of antimurine IL-6 antibody on survival and host defense were studied in a clinically relevant model of infection. METHODS: Balb/c mice were treated with 10 micrograms of antimurine interleukin-6, a nonspecific mouse IgG, or placebo 1 hour before they underwent bacterial challenge by gavage of 10(10) Escherichia coli and burn injury. Survival and the extent of translocation of E coli were determined as well as the correlation between the IL-6 levels and survival times. RESULTS: Survival after burn and gavage was 90% in animals treated with antimurine interleukin-6 vs 50% in animals treated with nonspecific IgG and 30% in saline-treated controls. A significant correlation between the levels of IL-6 and survival time was observed. Less translocation and better killing of bacteria were observed in the tissues of animals treated with antimurine interleukin-6. CONCLUSIONS: Interleukin-6 appears to play a major role in both the intensity of translocation of E coli from the intestine following burn injury and the host's ability to kill translocated organisms. Improved outcome was associated with a reduction of IL-6 levels by anti-IL-6 antibody.

Analysis of Variance↗

PubMed1994

IFN-gamma decreases translocation and improves survival following transfusion and thermal injury.

The effects of recombinant murine interferon-gamma (rmIFN-gamma) on survival and host defense were studied during gut-derived sepsis that included transfusion-induced immunosuppression. Balb/c mice (n = 153) were transfused with allogeneic blood and then treated with different doses of rmIFN-gamma: 10, 100, 1000, 10,000 U, or sterile saline as control once daily for 3 days. Five days after transfusion they were gavaged with 10(10) Escherichia coli and given a 20% TBSA burn injury. Survival was significantly higher in groups receiving 10 U compared to control and the group receiving 10,000 U (P < 0.0001 and P = 0.02, respectively). Groups receiving 100 or 1000 U also showed an improvement of survival compared to nontreated control animals (P = 0.02). The effect of rmIFN-gamma on the degree of translocation and the host's ability to kill translocated organisms was also investigated. Mice were treated as described above, except they were gavaged with 111In oxine-labeled E. coli and then subjected to a 20% TBSA burn. Mesenteric lymph nodes (MLN), liver, and spleen were harvested aseptically. Less translocation to the liver was observed compared to the nontreated group (P = 0.002) to the MLNs and spleen of the group treated with 100 U rmIFN-gamma compared to controls and the group treated with 10 U (P < 0.005). Animals receiving 1000 U showed fewer bacteria in the liver and spleen compared to the control group (P < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Granulocyte macrophage colony-stimulating factor improves survival in two models of gut-derived sepsis by improving gut barrier function and modulating bacterial clearance.

OBJECTIVE: The effect of recombinant murine granulocyte macrophage colony-stimulating factor (rmGM-CSF) on survival and host defense was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression. SUMMARY BACKGROUND DATA: Granulocyte macrophage colony-stimulating factor improves resistance in several models of infection, but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined. METHODS: Balb/c mice were treated with 100 ng of rmGM-CSF or placebo for 6 days in a model of transfusion, burn, and gavage, or cecal ligation and puncture (CLP). Translocation was studied in the first model. RESULTS: Survival after transfusion, burn, and gavage was 90% in rmGM-CSF-treated animals versus 35% in the control group (p < 0.001). After CLP, survival was 75% in the rmGM-CSF group versus 30% in the control group (p = 0.01). Less translocation and better killing of bacteria was observed in the tissues in animals treated with rmGM-CSF. CONCLUSION: The ability of rmGM-CSF to improve gut barrier function and enhance killing of translocated organisms after burn injury-induced gut origin sepsis was associated with improved outcome. Granulocyte macrophage colony-stimulating factor also improved survival after CLP.

Animals↗

PubMed1994

Heparan sulfate increases survival during gut-derived sepsis by decreasing bacterial translocation and enhancing host defense.

The effect of heparan sulfate (HS) on survival rate, bacterial translocation, and host defense was studied in a model of gut-derived sepsis that included transfusion-induced immunosuppression. Balb/c mice were treated pre- and postburn injury and bacterial challenge with HS, 5 mg/kg/day, or sterile phosphate-buffered saline. The HS pre- and postburn treated animals showed a significant improvement in survival compared to control animals (80 vs. 30%, p = .004, and 60 vs. 20%, p = .02, respectively). A lower amount of translocation was observed in the spleen (p < or = .001) of the HS group compared to control group. Quantitative colony counts and the calculated percentage of viable bacteria showed that the ability to kill translocated organisms was enhanced in all tissues of the animals receiving HS. These data suggest that treatment with HS positively affects the outcome in gut-derived sepsis. The beneficial effect was related both to an improved gut barrier function and to an enhanced host defense.

Analysis of Variance↗

PubMed1994

Effects of surgical trauma of laparoscopic vs. open cholecystectomy.

The effects of surgical trauma resulting from laparoscopic cholecystectomy and open cholecystectomy, were compared by assessing the postoperative acute phase alterations of selected plasma proteins, hormones and lymphocyte subpopulations in fifty-seven patients prior to elective cholecystectomy. Patients were prospectively randomized to undergo either laparoscopic cholecystectomy (n = 30) or open cholecystectomy (n = 27). Duration of operation and general anesthesia was similar in the two patient groups. The laparoscopic cholecystectomy patients had a shorter postoperative stay in hospital (3.1 (0.5) days vs. 7.1 (1.6) days; p < 0.001). In open cholecystectomy patients a significantly greater postoperative acute phase increase in plasma C-reactive protein (p < 0.001), cortisol (p < 0.05), and prolactin blood level (p < 0.001) was recorded. The postoperative acute phase decrease in the blood total-T-lymphocyte count (CD3 cells) and in the activated-lymphocyte count (OKDR cells) was significantly greater after open cholecystectomy (p < 0.05). These results, showing that acute phase responses are less marked after laparoscopic cholecystectomy than after open cholecystectomy, support the concept that the laparoscopic procedure is less traumatic.

Acute-Phase Reaction↗

PubMed1980