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Biomedical subjects

W G Cheadle

Publications and source records attributed to W G Cheadle.

At least 37 records · Page 2Linked to original sources
PubMed1998

Neutrophil migration into the peritoneum is P-selectin dependent, but sequestration in lungs is selectin independent during peritonitis.

Neutrophil (PMN) influx into the peritoneal cavity in response to bacterial peritonitis is an indispensable aspect of host defense. PMNs also are responsible for the remote organ injury observed after major abdominal infection. The aim of this study was to examine the effect of selectin blockade on PMN migration into the peritoneum and on PMN sequestration in the lungs, early in the course of peritonitis. Cecal ligation and puncture (CLP) was performed on P-selectin-deficient (P-def) mice and their genetic controls (C57). Both groups were treated with anti-E-selectin antibody, anti-L-selectin, or isotypic control immunoglobulin G at the time of CLP. 6 h after CLP, mice were sacrificed. Peritoneal PMN migration decreased in P-def mice compared with C57 controls after CLP. Blockade of E- or L-selectin alone in controls did not alter peritoneal PMN influx or circulating PMNs after CLP. In the P-def mice, treatment with anti-E-antibody or anti-L-antibody nearly eliminated PMN influx into the peritoneum. In contrast, circulating PMNs markedly increased after CLP in P-def mice when compared with baseline values. Lung myeloperoxidase increased in all groups of mice following CLP. Blockade of P-selectin with anti-P-selectin antibody elicited a response similar to that observed in the P-def mice. In conclusion, P-selectin mediates PMN influx into the peritoneal cavity, while E- and L-selectins do not appear to play any significant role in the 6 h time period following CLP. Lung PMN sequestration, after CLP, occurred independent of P-, E-, or L-selectin expression. Blockade of P-selectin during peritonitis appears to be potentially deleterious by preventing early PMN influx into the compartment containing the septic focus.

Animals↗
PubMed1997

Treatment of pneumonia in mechanically ventilated trauma patients. Results of a prospective trial.

OBJECTIVES: To determine the efficacy and magnitude of associated adverse effects of 2 different antibiotic regimens for the treatment of pneumonia in intubated surgical patients and to assay and compare blood samples and bronchoalveolar lavage fluid with respect to some host-defense parameters, especially in patients with unilateral pneumonia. DESIGN: Randomized, prospective, unblinded clinical comparison of 2 treatment arms with respect to intent to treat and clinical and microbiologically evaluable patients. SETTING: Six university surgical services in teaching hospitals with modern and well-staffed intensive care units. INTERVENTIONS: The consistency and objectively of the diagnosis of pneumonia was improved by the use of a grid of diagnostic parameters. Aggressive mechanical approaches to pneumonia in intubated surgical patients were supplemented by therapeutic use of aztreonam and vancomycin hydrochloride or combined imipenem and cilastatin sodium. RESULTS: Patients randomized to the aztreonam-vancomycin group were somewhat more ill, fared slightly better, and had fewer serious drug-related side effects than did those treated with imipenem-cilastatin (all P > .05). Immunologic parameters assessed by evaluation of bronchoalveolar lavage fluid showed differences between infected pulmonary lobes and noninfected ones; some changes were also noted in patients who recovered compared with those whose pneumonia persisted or recurred. CONCLUSIONS: Clinical studies of pneumonia in surgical patients need to be stratified to assure comparability, to identify patients in whom treatment is likely to fail, and to display differences between more and less effective therapies. Studies of blood and bronchoalveolar lavage samples showed that certain local and systemic immunologic parameters correlate with clinical status and outcome.

Aztreonam↗
PubMed1997

The pulmonary inflammatory response to experimental fecal peritonitis: relative roles of tumor necrosis factor-alpha and endotoxin.

The roles of endotoxin (LPS) and tumor necrosis factor-alpha (TNF-alpha) in the causation of organ injury during sepsis are unclear. To study LPS and TNF-alpha in the genesis of lung inflammation after cecal ligation and puncture (CLP), we used endotoxin-resistant (C3H/HeJ) and endotoxin-sensitive mice (C3H/HeOuJ). We examined lung neutrophil sequestration, interleukin 1 (IL-1)beta mRNA expression, IL-1 beta protein expression, and injury. We also determined the expression of two C-X-C chemokine mRNAs, macrophage inflammatory protein-2 (MIP-2) and KC, in the lung to determine whether in vivo, endotoxin, or TNF-alpha are significant modulators of MIP-2 and KC mRNA expression. After CLP, increased neutrophils sequestrated in the lungs of both strains of mice and coincided with an increase in expression of IL-1 beta, MIP-2 and KC mRNAs, and IL-1 beta protein. Lung and serum TNF-alpha were significantly increased in the C3H/HeOuJ strain but not in the C3H/HeJ strain. Histologic studies of the lung revealed similar injury in both strains. Our results suggest that bacterial factors other than endotoxin cause lung neutrophil sequestration and injury after CLP and, further, that TNF-alpha production is not a prerequisite. Our findings also suggest a potential role for local pulmonary chemokine production in the control of neutrophil sequestration after CLP.

Animals↗
PubMed1997

Poor outcome from peritonitis is caused by disease acuity and organ failure, not recurrent peritoneal infection.

OBJECTIVE: The purpose of the study is to determine whether organ failure develops in patients despite control of peritoneal infection and whether the process is, in part, neutrophil (polymorphonuclear leukocyte [PMN]) mediated. SUMMARY BACKGROUND DATA: Peritonitis generally responds to prompt surgical intervention and systemic antibiotics; however, some patients continue a septic course and progress to organ failure and death. METHODS: One hundred five consecutive patients with peritonitis between 1988 and 1996 who required operation and a postoperative hospital stay greater than 10 days were studied. Mice were injected with a monoclonal anti-PMN antibody 24 hours before cecal ligation and puncture (CLP) to deplete PMNs. RESULTS: Thirty-eight patients died, and all but 1 had identified organ failure. Seventy-seven patients had either pulmonary failure alone (25 patients) or as a component of multisystem organ failure (52 patients). All but one of these patients showed resolution of their intraperitoneal infection as evident by clinical course, abdominal computed tomographic scan, second-look laparotomy, or autopsy. Recurrent intra-abdominal infection developed in 15 patients, but only 1 had organ failure, and 2 died. At 18 hours after CLP, lung injury, PMN content, interleukin-1 mRNA expression, and liver injury were significantly reduced by anti-PMN treatment, whereas serum endotoxin levels actually increased. CONCLUSIONS: Disease acuity and organ failure, and not recurrent peritoneal infection, are the major causes of adverse outcome in patients with peritonitis. The authors' experimental data indicate that such organ injury is, in part, PMN mediated but not endotoxin mediated. Attraction of PMNs toward the site of primary infection, and thereby away from remote organs, is a logical future therapeutic approach in such patients who are critically ill with peritonitis.

APACHE↗
PubMed1997

Inhibition of neutrophil migration at the site of infection increases remote organ neutrophil sequestration and injury.

Up-regulation of the leukocyte beta 2 integrin, CD18, is a key event in neutrophil-endothelial adhesion and neutrophil-mediated organ injury. Inhibition of CD18 with monoclonal antibodies reduces lung and liver neutrophil sequestration in animal models of Gram-negative bacteremia or endotoxemia. However, with a persistent septic challenge, interference with host leukocyte phagocytic defense could adversely affect outcome. To assess the effects of inhibiting CD18 on organ neutrophil responses, bacteremia, and organ injury after fecal peritonitis, mice underwent cecal ligation and puncture (CLP). At the time of CLP and 12 h later, mice received intravenous anti-CD18 antibody or control IgG. At 3, 6, and 18 h after CLP, lung and liver tissue neutrophil content were measured by myeloperoxidase (MPO) assay, peritoneal cells and blood leukocytes were differentially counted, blood was cultured, and serum aspartate aminotransferase was measured. There was a significant reduction in peritoneal neutrophil migration and an increase in blood neutrophils after anti-CD18 treatment compared with results from treatment with the control antibody. In the anti-CD18-treated group, liver MPO was increased fivefold at 6 and 18 h, while lung MPO was increased two-fold at 18 h when compared with the control antibody-treated group. The anti-CD18-treated group also had an increase in bacteria cultured from the blood at 6 and 18 h and an increase in serum aminotransferase at 18 h. Our data demonstrate that peritoneal neutrophil migration in response to an endogenous fecal challenge is CD18-dependent, and that this mechanism forms a vital part of host defense. Inhibition of CD18 increased neutrophil sequestration in the liver and lung and increased liver injury. This study demonstrates a paradoxical increase in organ neutrophil sequestration using a leukocyte anti-adhesion therapy during sepsis and suggests that anti-adhesion therapies targeted towards neutrophil may worsen outcome if given during an ongoing, localized infection.

Animals↗
PubMed1997

A new standard of care: administration of preoperative antibiotics in the operating room.

Surgical site infections increase total hospital expenses and extend the length of hospital stay. Properly administered antibiotics are successful in minimizing postoperative subcutaneous wound infection secondary to perioperative bacterial contamination at the surgical site and are effective in most clean-contaminated surgical procedures. It is imperative that therapeutic levels of antibiotics be present during the time when the wound is open to maximize their effect to prevent the development of surgical wound infections. Only 32 per cent of 97 patients sampled from 1992 to 1994 at the Louisville Veterans Affairs Medical Center were administered preoperative antibiotics within 1 hour prior to surgical incision. Changing the responsibility for preoperative antibiotic administration from ward or holding room nurses to the anesthesiologist in the operating room rendered such antibiotics delivered closer to the induction of anesthesia and subsequent incision. Eighty-eight per cent of 220 patients sampled in 1995 had antibiotics administered within 1 hour of incision. This change in institutional policy of antibiotic administration maximizes the likelihood of appropriate antibiotic tissue levels and thereby their potential efficacy. Routine prophylaxis should be administered as close to the time of induction of anesthesia as possible to provide the best chance for appropriate tissue levels above the minimum inhibitory concentration for potential bacterial contamination.

Antibiotic Prophylaxis↗
PubMed1996

Antibiotic efficacy against Staphylococcus epidermidis adherent to vascular grafts.

Antibiotic bonded grafts may improve the treatment results of vascular graft infections. The purpose of this study was to determine the antibiotic and antibiotic concentration needed to be effective against Staphylococcus epidermidis-infected vascular grafts. The efficacy of four antibiotics (minocycline, cefazolin, vancomycin, and rifampin) against S. epidermidis adherent to Dacron or Teflon vascular grafts was studied in vitro. Kill kinetic studies were performed with 18 and 42 hr of exposure of Dacron-adherent and Teflon-adherent S. epidermidis at 1, 4, 16, and 64 times the minimum inhibitory concentration (MIC) of each antibiotic. Antibiotic efficacy against graft-adherent S. epidermidis at 42 hr was best at concentrations 64x MIC for minocycline, cefazolin, and vancomycin and 4x MIC for rifampin. None of the antibiotics totally eradicated the graft-adherent bacteria. Antibiotics were equally effective for S. epidermidis adherent to Dacron and Teflon grafts. Antibiotic concentrations several times that predicted by the MIC were needed for all antibiotics to achieve significant killing of graft-adherent bacteria, with rifampin the most effective at the lowest concentration.

Anti-Bacterial Agents↗
PubMed1996

CD14 expression in injured patients correlates with outcome.

OBJECTIVE: The authors determined the correlation between monocyte CD14 expression and outcome in severely injured patients. SUMMARY BACKGROUND DATA: Human leukocyte antigen-DR (HLA-DR) expression CD14 positive monocytes correlates with the development of major infection and subsequent death in severely injured patients. Recent studies show that CD14 is not only a marker for mature monocytes, but also is an important endotoxin/lipopolysaccharide receptor. METHODS: Flow cytometry data obtained by dual staining techniques (CD14 and HLA-DR) of monocytes in 213 severely injured patients were analyzed over a 30-day period. Outcome criteria included survival and the development of both major and minor infections. RESULTS: The percentage of cells expressing CD14 (%CD14) correlated with clinical outcome, reaching significance (p < 0.05) between noninfected survivors (n = 74) and nonsurvivors (n = 21) at days 3, 7, 11, 17, 24, and 30. At days 3, 7, and 17, the %CD14 also was different between noninfected and infected survivors. After 7 days, differences were only seen between survivors and nonsurvivors (p < 0.05). The mean fluorescence intensity (MC CD14) in monocytes of all patients was significantly reduced at day 3 compared with day 1 and remained low for 30 days (p < 0.05). The nonsurvivor group had consistently low MC CD14 values, which were significant at day 5 (p < 0.05). CONCLUSIONS: In addition to HLA-DR expression, CD14 expression on monocytes is an indicator of clinical outcome after injury and could represent a more precise target for treatment.

Adolescent↗
PubMed1996

Fluid resuscitation attenuates early cytokine mRNA expression after peritonitis.

OBJECTIVE: To study the hypothesis that fluid resuscitation alters cytokine gene expression after experimental murine peritonitis. MATERIALS AND METHODS: Mice underwent cecal ligation and puncture (CLP) to induce peritonitis and were randomized to receive variable amounts of normal saline (0, 0.25, 1.0 ml. subcutaneously) and serum (0 or 0.1 mL) after operation. Hepatic and small intestinal (ileal) tissue were harvested at 3 or 6 hours after CLP, and total tissue RNA was extracted. Reverse transcriptase polymerase chain reaction was used to provide relative quantitation of tumor necrosis factor-alpha and interleukin (IL)-1 beta messenger RNA (mRNA) compared with beta-actin. RESULTS: CLP without resuscitation resulted in significant increases in hepatic tumor necrosis factor-alpha mRNA (1190% at 6 hours compared with normal animals), and IL-1 beta mRNA (1475%), and intestinal IL-1 beta mRNA (1243%). Volume administration attenuated cytokine expression at both 3 and 6 hours, and saline seemed to have more potent effects than serum. The volume of resuscitation correlated with survival at 18 hours. Survival in the saline (1 mL) + serum group was 90% at 18 hours compared with 20 to 40% in the groups with little or no resuscitation. Overall, there were no survivors at 30 hours. CONCLUSIONS: Fluid resuscitation (amount, composition, timing) should be an important consideration in the utilization of experimental infection models. Furthermore, optimization of the patient's intravascular volume status during sepsis may have important effects on immune responses, in addition to improving hemodynamic variables.

Animals↗
PubMed1996

Postoperative nasogastric decompression: a prospective randomized trial.

To determine which type of patient should receive routine postoperative nasogastric decompression (NGD), we observed 76 patients who were randomized into two groups: those who received routine NGD (n = 39) and those who received selective NGD (n = 37). Eighteen patients in the selective NGD group never required intubation, while 19 did require intubation within a mean of 3 days after surgery. In both groups, tubes remained in place for a mean of 4.7 days. The routine NGD group had a 2.5% incidence of emesis, while the selective NGD group had a 51% incidence of emesis. The return of bowel function, return to a regular diet, and postoperative length of hospital stay were similar in both groups. The patients in the selective NGD group who did not require intubation had a shorter postoperative stay. Fifty-eight percent of patients in the selective NGD group who required intubation had had major vascular or retroperitoneal dissections. These data support selective use of NGD in general surgical patients and routine use of NGD for patients having major retroperitoneal or vascular procedures.

Diet↗
PubMed1996

Sepsis and septic complications in the surgical patient: who is at risk?

The estimation of patients who are at risk for infection, sepsis, and organ dysfunction/failure is crucial not only for inclusion in treatment algorithms but also for entry into appropriate clinical trials of prophylaxis and therapy. Patients on the surgical service who have sustained major trauma or who have undergone transplantation are clearly at the greatest risk. Other immunosuppressed patients at risk for sepsis include those receiving myelosuppressive chemotherapy, those with overwhelming malignancy, and those who suffer from cirrhosis, diabetes mellitus, and severe malnutrition. We have focused on the trauma patient, in whom infection and organ failure are the leading causes of late death, major morbidity, and prolonged hospital stay. Over a 10 yr period, we have surveyed a number of host defense parameters that pertain to an adequate immune response and found a suppressed response shortly after injury in many. All were anergic to a standard skin test panel, and the duration of anergy varied with the clinical course of infection. Immunoglobulin levels were low after major injury as well as specific antibodies to both Gram-positive and Gram-negative organisms. The ability of serum from the trauma patient to opsonize heat-killed bacteria was markedly depressed 24 h after injury in those patients who subsequently died of infection. Class II major histocompatibility antigen expression on peripheral blood monocytes correlated closely with clinical outcome and led to the development of an Outcome Predictive Score. This score can identify patients within hours of hospitalization who are at risk of subsequently developing overt clinical infection and sepsis. Intervention then can be applied to such at-risk populations prior to the onset of sepsis and to evaluate the efficacy of prophylaxis. Patients in whom prophylaxis fails could be eligible for trials of therapeutic intervention as well.

Cytokines↗
PubMed1995

Immunosuppression augments growth of graft-adherent Staphylococcus epidermidis.

OBJECTIVE: To determine if systemic suppression of host defenses during graft implantation alters the initial adherence and subsequent growth of Staphylococcus epidermidis on vascular prostheses. DESIGN: Dacron grafts 1 cm2 were implanted in the back subcutaneous tissue of Swiss-Webster mice (n = 247), followed by topical inoculation with 2 x 10(7), 2 x 10(5), 2 x 10(3), or 2 x 10(1) colony-forming units of S epidermidis. Half of the mice were immunosuppressed with cyclophosphamide (150 mg/kg intraperitoneally), to achieve a consistent, significant decrease in the white blood cell count and major histocompatibility complex class II (Ia) expression. Control mice received an equal volume of saline solution. Graft bacterial biofilm concentrations were determined at 1 day for adherence and within 2 weeks for bacterial growth, by using sonication and quantitative agar culture. RESULTS: Immunosuppression did not significantly alter the initial adherence of bacteria to vascular grafts. Immunosuppressed animals that were inoculated with 2 x 10(7) and 2 x 10(5) colony-forming units of S epidermidis had significantly higher bacterial biofilm concentrations as compared with those in control animals. Graft infection persisted at 14 days in all animals, with and without immunosuppression. CONCLUSIONS: Suppression of immune function during graft implantation augmented growth of adherent bacteria. The effect of short-term perioperative immunosuppression on late-appearing S epidermidis graft infection needs further study.

Animals↗
PubMed1995

Hemorrhagic shock-induced alterations in circulating and bronchoalveolar macrophage nitric oxide production.

Local and systemic host immune functions are markedly altered after trauma. Activated macrophages (M phi) are the major effector cells of protective immunity, mediated in part by nitric oxide (NO). This study was undertaken to determine the effects of hemorrhage (HEM) on M phi cytotoxic function as measured by NO production. Male Sprague-Dawley 350- to 400-g rats were studied. Sham animals only had their carotid artery exposed and ligated. Hemorrhaged animals had carotid artery cannulation followed by HEM to SBP of 40 mmHg, sustained for 45 min, followed by resuscitation with shed blood and crystalloid. Recovered animals were sacrificed (n = 5 each) at 6, 12, 24, and 72 hr after HEM; blood and alveolar M phi were then isolated and examined. A monolayer of adherent M phi was examined for NO production in resting state and after in vitro LPS stimulation. (1) HEM resulted in significantly reduced alveolar M phi yield at 12 and 24 hr. (2) HEM increased NO production by circulating M phi at 24 hr (P < 0.05), while alveolar M phi had significantly increased NO production at all time points after HEM (P < 0.05). (3) LPS stimulation significantly increased NO production in both circulating and alveolar M phi in sham animals and 6 hr after HEM but not at any other times. We therefore conclude that HEM causes early and prolonged activation of NO production by alveolar M phi and delayed and brief activation of circulating M phi. Alveolar and circulating M phi are unable to significantly increase NO production in response to LPS stimulation during the later phases of HEM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Peritoneal host defenses are less impaired by laparoscopy than by open operation.

There is a growing body of evidence that laparoscopic surgery is physiologically less injurious than open surgery. We hypothesized that the open technique results in a greater impairment of peritoneal and systemic defense mechanisms than does the laparoscopic technique. Nissen fundoplication, standardized in technique and duration, was performed in 16 pigs. The procedure was performed through a standard midline incision (OPEN, n = 8) or with laparoscopic technique and CO2 pneumoperitoneum (LAP, n = 8). The peritoneal cavity was instilled with 400 cc of normal saline, either alone (not contamined, n = 8) or containing 10(9) E. coli/ml (contaminated, n = 8). Quantitative cultures, cell count, and flow cytometry were performed on blood and peritoneal fluid samples obtained at timed intervals. We found that host defense processes were better preserved after LAP than by OPEN surgery. Peritoneal and systemic monocyte class II antigen expression, and serum tumor necrosis factor-alpha activity was greater in the OPEN group compared with the LAP group, but peritoneal bacterial clearance was more efficient in the LAP group. These data may illustrate a potential benefit of laparoscopic surgery in cases of peritoneal contamination.

Animals↗
PubMed1995

Second place winner of the Conrad Jobst Award in the gold medal paper competition. Increased antibiotic effectiveness in a model of surgical infection through continuous infusion.

As long as infection remains the most common cause of morbidity and mortality in severely ill patients, there exists the need for more effective anti-infective therapy. The current study was undertaken to determine whether continuous infusion (CONT) is superior to intermittent administration (INT) of an equal amount of cefazolin (CEF) in a model of surgical infection. The thigh suture model consists of the surgical placement of 1 cm of cotton suture with absorbed K. pneumoniae into the thigh muscle of mice. The experimental groups were: 1) controls (n = 20) with thigh suture inoculation and treatment with intraperitoneal (IP) sterile saline; 2) CONT infusion group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by CONT IP infusion at 180 mg/kg/day (n = 22) for 3 days; and 3) INT injection group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by INT IP injections every 8 hours at 180 mg/kg/day (n = 20) for 3 days. All CEF treated animals received identical quantities of total CEF, and all groups were followed for 10 days. The control and INT CEF groups had 20% survival, whereas the CONT CEF group had 81% survival, (P < 0.001). Continuous CEF yielded constant serum levels of 19 +/- 1 micrograms/mL, whereas INT injections resulted in peak serum level of 74 +/- 12 micrograms/mL at one minute but declined to 3.9 +/- 0.9 micrograms/mL in 2 hours. Although there was statistically significant tissue bacterial growth in the INT injection group, there was extensive tissue bacterial clearance in the CONT infusion group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Endothelin-1 expression in the small intestine during chronic peritonitis.

Endothelins (ET) have been demonstrated to mediate intestinal microvascular constriction during acute Escherichia coli bacteremia, however, their role during chronic infection is unknown. The purpose of this study was to determine whether ET-1 is synthesized in the small intestine in a more chronic peritonitis model. ET-1 mRNA levels of the terminal ileum in mice following cecal ligation and puncture (CLP) were compared to sham-operated animals and normal unoperated animals. ET gene expression was analyzed using differential reverse transcriptase chain reaction (RT-PCR) with co-amplification of beta-actin as an internal standard. To assess ET peptide expression, serum and intestinal tissue levels were measured using a specific enzyme immunoassay (ELISA). The pattern of ET-1 gene expression post-CLP with a single puncture of the cecum with a 23 ga. needle demonstrated a 3.6-fold increase at 8 h, and a return to sham levels by 24 h (374 +/- 64% at 8 h, p < .05, 128 +/- 13%). An increase of mRNA levels at 24 h post-CLP was observed with a double puncture with an 18 ga. needle (230 +/- 36%, p < .05) accompanied by an increase in serum ET levels (270 +/- 31%, p < .05) and higher tissue ET levels. These data indicate a time-dependent response of ET-1 gene expression in the terminal ileum post-CLP which is related to severity of infection.

Animals↗
PubMed1994

Improved survival in simulated surgical infection with combined cytokine, antibiotic and immunostimulant therapy.

A study was performed to find an ideal combination and sequence of cytokines, antibiotics and immunorestorative agents to enhance survival from serious infection. The effects of combinations of granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor (TNF) alpha, the immune adjuvant muramyl dipeptide (MDP) and two systemic antibiotics were studied in a validated murine model of surgical infection. A single cotton suture containing absorbed Klebsiella pneumoniae was placed into the thighs of mice to produce local and systemic infection. Control mice received a volume of subcutaneous saline equal to that of the therapeutic agent; only 18 per cent survived 9 days after infection. The survival time of mice treated with any single agent was similar to that of controls. The group given maximal combined therapy (65 mice) received GM-CSF, TNF-alpha, MDP, and ampicillin-sulbactam or cefoxitin for 6 days. The survival rate in this group 9 days after the introduction of infection was 84-90 per cent (P < 0.0001), suggesting that specific combinations of cytokines, immunostimulants and antibiotics may be useful in combating lethal infection.

Acetylmuramyl-Alanyl-Isoglutamine↗