Interleukin-4 prevents mortality from acute but not chronic murine peritonitis and induces an accelerated tumor necrosis factor-alpha response.

Interleukin-4 (IL-4) demonstrates properties in vitro that suggest an anti-inflammatory role in the immune response, one of which is the inhibition of tumor necrosis factor-alpha (TNF) release. We examined the effects of IL-4 administration on mortality and serum TNF levels in two murine models of peritonitis. Animals infected with intraperitoneal injections of Escherichia coli and Bacteroides fragilis (acute peritonitis) had a decreased mortality and earlier TNF-alpha peak when pretreated with 5,000 units IL-4. Animals infected with bacteria and a sterile fecal adjuvant (chronic peritonitis) had no alteration in mortality or serum TNF levels (which were consistently low) with IL-4 pretreatment. These data demonstrate that, under some in vivo conditions, IL-4 can significantly ameliorate a septic insult, but this effect appears to be highly model-dependent and not clearly related to its effects on TNF-alpha.

Comparison of APACHE II scoring in liver and kidney transplant recipients versus trauma and general surgical patients in a single intensive-care unit.

Over a 26-month period we assessed the ability of APACHE II, scored on admission to the surgical intensive care unit (SICU), to predict the in-hospital mortality of liver and kidney transplant recipients either post-operatively or after subsequent complications, and compared these results to non-transplant SICU admissions. There were 866 SICU admissions, of which 128 were liver transplant recipients, 112 were renal transplant recipients, 211 were trauma admissions and 415 were non-transplant/non-trauma admissions. In hospital mortalities among all liver transplant admissions were 0%, 10%, 38%, and 82% for APACHE II ranges of 0-10, 11-20, 21-30 and > 30, respectively, with differences between the second and third, and third and fourth ranges significant (p < or = 0.05 by chi-square analysis). These differences were also seen when examining scores following the primary transplantation alone. Mortalities in corresponding APACHE II ranges for trauma and nontransplant/nontrauma admissions were similar. APACHE II scoring was not useful for renal transplant recipient, as it consistently overpredicted mortality. We conclude that APACHE II scoring may be useful in predicting outcome in post-operative liver transplant recipients, but is not useful in stratifying risk in renal transplant recipients due to the inherently low mortality involved.

CD4+ T cells mediate preexposure-induced increases in murine intraabdominal abscess formation.

We have previously shown that an increased number of Escherichia coli/Bacteroides fragilis intraabdominal abscesses are produced in mice after preexposure to small numbers of live E. coli or B. fragilis. Splenic lymphocyte subset changes and the importance of different elements of the immune response in this system were studied. Preexposure to bacteria induced a significant increase in the percentage of splenic T cells without altering the CD4/CD8 ratio. The passive transfer of either 10(7) mixed splenic lymphocytes, 5 x 10(6) mixed T cells, or 2.5 x 10(6) CD4+ T cells from preexposed animals to naive siblings 24 hr prior to abscess induction resulted in increased abscess formation. Transfer of serum, B cells, < 10(7) lymphocytes, CD8+ T cells, or any cell type from naive animals did not change abscess number. The bacterial composition of abscesses changed only in animals receiving either serum or B cells from donors preexposed to B. fragilis, where an increased number of B. fragilis per abscess was found. The CD4+ T cell response can be altered by transient infections and is critical to subsequent abscess formation, and a concurrent humoral response may play a role in determining an abscess' ultimate bacterial composition.

The role of Candida albicans in the pathogenesis of experimental fungal/bacterial peritonitis and abscess formation.

The recovery of Candida albicans along with bacteria from the abdomen in the setting of peritonitis is becoming increasingly common. It is not known whether the interactions between the fungal and bacterial elements of these infections are synergistic, competitive, or neutral. To study this question, we have examined the effects of both the addition of C. albicans to a solely bacterial infection caused by Escherichia coli and Bacteroides fragilis, and the deletion of various components of this system using directed antimicrobial therapy. In a mixed infection, both C. albicans and bacteria contributed to mortality, since only the combination of cefoxitin and amphotericin B improved survival (from 50% to 90%). The addition of C. albicans to the bacterial inoculum increased the recovery of abscesses, but only to the number seen with fungal infection alone, implying two fairly independent processes. Although the number of bacteria recovered from abscesses at 10 days postinfection was unchanged with the addition of fungi, the deletion of the bacterial component of mixed infections led to the overgrowth of C. albicans. We conclude that this model of mixed C. albicans/E. coli/B. fragilis peritonitis is best characterized as two nonsynergistic, parallel infections with incomplete competition, allowing the survival of all three organisms to eventual abscess formation.

Effectiveness of fluconazole in murine Candida albicans and bacterial C. albicans peritonitis and abscess formation.

The role of fluconazole in the treatment of many forms of focal mycoses remains unclear. We studied the effectiveness of three different oral doses of fluconazole in three murine models of Candida albicans peritonitis leading to intra-abdominal abscess formation. During monomicrobial Candida infection, fluconazole decreased mortality and the number of C. albicans cultured per abscess; prolonged treatment also eliminated Escherichia coli translocation. In mixed C. albicans/E. coli/Bacteroides fragilis infection, prolonged treatment with higher doses of fluconazole decreased mortality, the number of abscesses formed, and the number C. albicans per abscess. In animals with a similar polymicrobial infection but with concurrent cefoxitin treatment, fluconazole decreased mortality and the number of C. albicans per abscess; in addition, prolonged treatment reduced the number of abscesses. Amphotericin B gave similar results in all three models. These data indicate that the clinical use of fluconazole in peritonitis should be investigated.

Development of Candida albicans and C. albicans/Escherichia coli/Bacteroides fragilis intraperitoneal abscess models with demonstration of fungus-induced bacterial translocation.

The development of models of both Candida albicans and mixed C. albicans/Escherichia coli/Bacillus fragilis peritonitis in immunologically normal mice are described, each with significant mortality and intra-abdominal abscess formation. C. albicans inoculated alone induced bacterial translocation into abscesses, and the addition of bacteria reduced the number of, but did not eliminate. C. albicans in abscesses. There was no synergy seen between fungi and bacteria in terms of either morbidity or mortality.

Prostaglandin E1 increases survival with extended anhepatic phase during liver transplantation.

OBJECTIVE: The authors investigated the intraoperative treatment effects of Prostaglandin E1 (PGE1) for extension of the anhepatic phase and improvement of survival in a rat liver transplant model. BACKGROUND: Cross-clamping the inferior vena cava and the portal vein during liver transplantation causes severe pathophysiologic changes during surgery. The time of the anhepatic phase is strictly limited and results in a very tenuous period during the liver transplant operation. METHODS: Prostaglandin E1 was infused at 0.5 microgram/kg/min into five subgroups of rats with 20, 30, 40, 60, and 80 minutes of anhepatic phase during transplantation. Bile secretion, serum aspartate transaminase (AST), lactic dehydrogenase (LDH), and blood gas analysis were studied in the 30-minute subgroup. The results were compared with the sham-operated and control groups. RESULTS: Intraoperative treatment with PGE1 extended the maximal anhepatic phase from 30 minutes in the sham-operated group up to 80 minutes, and increased survival. Significant changes in the PGE1 treated rats in the 30-minute subgroup included an increase of bile flow and bile salt output and decrease of AST and LDH activities after surgery. Blood gas analysis showed a decrease in acidosis and hypercarbia at the end of the anhepatic phase. CONCLUSIONS: The PGE1 treatment increased survival with extended anhepatic phase during rat liver transplantation. The beneficial effects can be attributed to its biologic activities.

Bile secretion and liver regeneration in partially hepatectomized rats.

OBJECTIVE: The purpose of this research was to study the correlation between bile secretion and the liver regeneration in the partially hepatectomized rat. SUMMARY BACKGROUND DATA: Significant alteration in bile formation and secretion is expected in the liver after hepatectomy. There is scant literature, however, about the effects of liver regeneration in bile secretion. METHODS: The work was done in rats with 50% hepatectomy, 75% hepatectomy, and sham operation as the control. A chronic common bile duct fistula and a duodenal cannula were established for bile collection and the sample analysis on days 1, 3, 5, 7, and 9. RESULTS: With size reduced in the liver after 50% and 75% hepatectomy, the total bile volume decreased 45.9% and 51.5%, bile salt independent flow decreased 59.3% and 64.9%, bile salt secretion rate decreased 36.1% and 43.4%, bile salt basal synthesis rate decreased 52.3% and 56.4%, phospholipid secretion rate decreased 52.6% and 68.0%, and cholesterol secretion rate decreased 54.3% and 72.4% from control on day 1, respectively. All changes returned to the control level in 3 to 9 days with accompanying increasing liver size during regeneration. CONCLUSION: Alterations of total bile flow, bile salt independent flow, bile salt secretion rate, bile salt basal synthesis rate, and biliary lipid secretion after partial hepatectomy correlate with the liver regeneration rate in rats. Partial hepatectomy reduces the bile salt independent fraction calculated as per 100 g body weight rather than the dependent fraction. The study of bile salt and biliary lipid secretion is a useful method for monitoring synthetic function in liver regeneration in vivo.

Pancreas cancer resection outcome in American University centers in 1989-1990.

BACKGROUND: Series of patients with pancreas cancer from single high-volume institutions or surgeons have demonstrated improvements in morbidity and mortality of pancreatic resection in recent decades. The experience of these single institutions or surgeons may not, however, reflect the results achieved by a cross-section of surgeons or hospitals. This article examines the resection outcome for a large unselected group of university hospitals and surgeons. METHODS: Pancreas cancer resection morbidity and mortality were examined using a multi-institution data base of discharge coding data from 26 American university hospitals. The data were analyzed for relationships of morbidity and mortality with the type of resection, patient age, hospital volume, and individual surgeon case load. RESULTS: Two hundred twenty-three resections were performed in 1989-1990 (pancreaticoduodenectomy, 168 patients; total pancreatectomy, 11; distal pancreatectomy, 30; and islet tumor resection, 14). The mortality rate was 6% (13 of 223) with major complications in 21%. Patient age did not correlate with complications or death. The surgeon case load ranged from 1-15 cases (median, 1) over the 2-year period. The mortality rate did not correlate with the case load. Surgeons performing one to three resections had significantly more complications than those performing four or more resections (P = 0.011). CONCLUSIONS: Pancreas resection is performed by an unselected cross-section of surgeons in American university centers with acceptable morbidity and mortality rates.

Successful paratopic pancreas transplantation: a report of three cases with venous portal drainage and enteric exocrine drainage.

Pancreatic transplantation is able to produce euglycemia in patients with Type I diabetes mellitus. Current surgical techniques utilize revascularization of the graft through the recipient iliac vessels and drainage of the exocrine pancreatic secretions through a duodenal conduit into the bladder. We describe a technique utilized in 3 patients whereby venous pancreatic drainage is into the portal venous circulation via the proximal splenic vein. The exocrine pancreatic secretions are drained into the proximal jejunum via a side-to-side donor duodenum to proximal small bowel anastomosis. Results and complications of this technique are presented. Potential short-term and long-term advantages and disadvantages of this technique are discussed. Our early experience suggests that paratopic pancreatic transplantation with venous drainage into the portal vein and exocrine drainage into the proximal jejunum is both feasible and desirable.

Anti-tumor necrosis factor antibody reduces mortality in the presence of antibiotic-induced tumor necrosis factor release.

The systemic tumor necrosis factor (TNF) response has been extensively studied during infection. In addition, antibiotics that cause cell-wall lysis have been associated with endotoxinemia and, therefore, could trigger TNF release. We studied the effects of pretreatment with cefoxitin and/or anti-TNF antibody on mortality and early (90 minutes) and delayed (6 hours) serum TNF levels in a murine model of mixed Escherichia coli/Bacteroides fragilis peritonitis. At low and intermediate inocula levels, cefoxitin, but not anti-TNF antibody, prevented death, and low serum TNF levels were noted in all groups. At the highest inoculum level, mortality was uniform in control, cefoxitin, and anti-TNF antibody groups, and a significant elevation in serum TNF levels was seen only at the 6-hour point in animals receiving cefoxitin. The addition of anti-TNF antibody to cefoxitin at this inoculum level abrogated the 6-hour rise in serum TNF levels and reduced mortality to 40%. These results emphasize that the cytokine response in disease is dependent on both the nature of the insult and other forms of therapeutic interventions.

A simple method for bile duct anastomosis and interval bile collection in the liver-transplanted rat.

A mini T-tube is introduced for the bile duct anastomosis of rat liver transplantation as well as interval bile collection. The validity of the T-tube was evaluated in 14 liver-transplanted rats and compared to 14 rats using traditional stent for bile duct anastomosis. Changes of biliary tree after the T-tube anastomosis were examined by T-tube cholangiography on sample rats at 4 days and at 4 months after liver grafting. Additionally, bile volumes and rates of bile salt secretion were compared in the continuously flowing cannula and the chronic T-tube fistula in normal rats. The results show that the mini T-tube facilitates bile duct anastomosis and study of bile secretion after liver transplantation in rats without increase in surgical difficulty or interference of biliary enterohepatic circulation.

Pancreas transplantation. An initial experience with systemic and portal drainage of pancreatic allografts.

Pancreas transplantation has evolved dramatically since its introduction in 1966. As new centers for transplantation have developed, the evaluation of complications associated with pancreas transplantation has led to advances in surgical technique. Furthermore, surgical alterations of the pancreas resulting from transplantation (systemic release of insulin and denervation) are of unproven consequence on glucose metabolism. Since 1988, the authors have performed 21 transplants (16 combined pancreas/kidney, 3 pancreas alone, which includes 1 retransplantation, 1 pancreas after previous kidney transplant, and 1 "cluster") in 20 patients aged 18 to 49 years; mean, 35 +/- 1 years. Overall patient survival is 95%. Three pancreatic grafts failed within the first year because of technical failure; one additional pancreas was lost to an immunologic event on postoperative day 449, for an overall pancreatic graft survival of 81%. No renal grafts were lost. To evaluate causes of graft failure, demographic data were compared, which included age and sex of the donor and the recipient, operative time, intraoperative blood transfusion, and ischemic time of the graft. No statistically significant differences were found between groups except for ischemic time (11.7 +/- 6.4 hours for the technical success group versus 19.8 +/- 3.7 hours for the technical failure group; p less than 0.05 by unpaired Student's t test). Quadruple immunosuppression was used, which included prednisone, cyclosporine, azathioprine, and antilymphoblast globulin. A mean of 1.2 (range, 0 to 3) rejection episodes per patient occurred. Mean hospital stay was 24 +/- 11 days. Surgical and infectious complications were evaluated by comparing the technical success (TS) group (n = 17) with the technical failure (TF) group. Surgical complications in the TS group revealed a mean of 1.3 episodes per patient, whereas the TF group had 3.7 episodes per patient. The TS also had a reduced incidence of infectious complications compared with the TF (1.7 versus 4.3 episodes per patient). Cytomegalovirus was common in both groups, accounting for 11 infectious episodes, and occurred on a mean postoperative day of 38. Mean postoperative HbA1C levels dropped to 5 +/- 1% from 11 +/- 3%. The authors developed a new technique that incorporates portal drainage of the pancreatic venous effluent in three recipients. Preoperative metabolic studies disclosed a mean fasting glucose of 211 +/- 27 mg/dL and a mean stimulated glucose value of 434 +/- 41 mg/dL for all patients; the mean fasting insulin was 23 +/- 4 microU/mL.(ABSTRACT TRUNCATED AT 400 WORDS)

Peritonitis into the 1990s: changing pathogens and changing strategies in the critically ill.

To study the effect of severe illness on the nature of peritonitis and intra-abdominal abscesses, the microbiology and clinical course of patients operated on over a 1-year period with culture-proven intra-abdominal infections whose preoperative Acute Physiology and Chronic Health Evaluation (APACHE) II scores were greater than or equal to 15 (predicted mortality at least 50%) were examined. Twenty-nine patients were enrolled, and overall mortality was 52 per cent, with increasing mortality correlating with higher APACHE II scores. The organism most commonly isolated from the peritoneum was Candida albicans, followed by Enterococcus species, Enterobacter species, and Staphylococcus epidermidis. An increase in the mean of the APACHE II scores on Days 3 and 7 compared to the preoperative score was associated with a 91 per cent mortality, while a decrease was associated with only a 22 per cent mortality. The authors conclude that the microbiology of intra-abdominal infections is inherently different in severely ill patients and that longitudinal clinical scoring may be more useful than a single scoring in predicting outcome. These data suggest that trials to investigate the broadening of standard perioperative antimicrobial coverage in the ill and use of longitudinal clinical scoring to direct aggressive reintervention may be warranted.

Complications requiring operative intervention after orthotopic liver transplantation.

Survival rates after liver transplantation continue to improve, but the postoperative morbidity in these patients remains significant. The clinical courses of 96 consecutive patients who received transplants were reviewed retrospectively. Forty-two patients experienced complications requiring surgical intervention. These complications were primarily related to biliary tract reconstruction, bowel complications, and septic complications. None of the factors examined, except a second transplant procedure, proved helpful in identifying those patients most likely to experience surgical complications; however, a risk factor scoring system was found to accurately identify that group of patients at highest risk of dying in the postoperative period. Only 2 of 21 deaths could be attributed directly to the surgical complication. We believe that a policy of prompt, aggressive surgical intervention, coupled with careful tailoring of immunosuppression to both the patient and the clinical situation, can lead to a low mortality rate in patients who require reoperation.