Open endotracheal tubes may be safely left on an ED airway cart for 48 hours.

OBJECTIVE: To determine if endotracheal tubes (ETTs) that are opened, prepared, and stored in an ED airway cart are prone to bacterial contamination. METHODS: A prospective study conducted in the ED of a level 1 trauma center. A study group of 50 endotracheal tubes were opened, preloaded with a stylet, the cuff checked for integrity by air inflation, and then stored in an ED airway cart. The study group was subdivided into 5 groups of 10 ETTs each, cultured at different time intervals. The ETTs were cultured at 6, 12, 24, 36, and 48 hours for the presence of bacterial contamination. The control group consisted of 10 ETTs that were left in their sterile packing in the ED airway cart and then removed at 48 hours and cultured. RESULTS: In the study group, 7 (14%) ETTs resulted in a positive culture; 43 ETTs cultured negative for bacteria. In the control group, 2 (20%) ETTs cultured positive, the remainder was all negative. There was no statistically significant difference between the 2 groups (P = .63). If only clinically significant bacteria are considered, defined as a culture with 5 or more colony-forming units, 3 ETTs in the study group cultured positive; there were no clinically significant bacteria cultured in the control group. Once again, there was no statistically significant difference between the 2 groups, with a P value of .57. CONCLUSION: It appears that opening, preparing, and storing ETTs in an ED airway cart for up to 48 hours does not increase the risk of bacterial contamination of the ETTs.

A (1-->3)-beta-D-linked heptasaccharide is the unit ligand for glucan pattern recognition receptors on human monocytes.

Glucans are fungal cell wall polysaccharides which stimulate innate immune responses. We determined the minimum unit ligand that would bind to glucan receptors on human U937 cells using laminarin-derived pentaose, hexaose, and heptaose glucan polymers. When U937 membranes were pretreated with the oligosaccharides and passed over a glucan surface, only the heptasaccharide inhibited the interaction of glucan with membrane receptors at a K(d) of 31 microM (95% CI 20-48 microM) and 100% inhibition. However, the glucan heptasaccharide did not stimulate U937 monocyte NFkappaB signaling, nor did it increase survival in a murine model of polymicrobial sepsis. Laminarin, a larger and more complex glucan polymer (M(w) = 7700 g/mol), only partially inhibited binding (61 +/- 4%) at a K(d) of 2.6 microM (99% CI 1.7-4.2 microM) with characteristics of a single binding site. These results indicate that a heptasaccharide is the smallest unit ligand recognized by macrophage glucan receptors. The data also indicate the presence of at least two glucan-binding sites on U937 cells and that the binding sites on human monocyte/macrophages can discriminate between glucan polymers. The heptasaccharide and laminarin were receptor antagonists, but they were not receptor agonists with respect to activation of NFkappaB-dependent signaling pathways or protection against experimental sepsis.

Agenesis of the gallbladder.

Agenesis of the gallbladder is rare. Three groups have been identified: those with multiple fetal anomalies, asymptomatic cases, and symptomatic cases. Right upper quadrant pain is present in 90% of the cases, nausea and vomiting in 60%, and jaundice in 35%. Operative strategy is aimed at thorough exploration to locate an aberrant gallbladder. We treated a 72-year-old woman with right upper quadrant pain, nausea, and vomiting but no fever or jaundice. Physical examination revealed right upper quadrant tenderness without rebound. The white blood cell count was 10,300/mm3. Total bilirubin level was 1.6 mg/dL. Ultrasonography revealed one gallstone and an enlarged common bile duct. Laparoscopic cholecystectomy was converted to open technique after failure to locate the gallbladder. On intraoperative cholangiogram, no gallbladder was identified. A T-tube was placed.

Superior mesenteric artery syndrome: an uncommon cause of intestinal obstruction.

Superior mesenteric artery (SMA) syndrome is an atypical cause of high intestinal obstruction, most frequently occurring in patients who have had rapid weight loss. Identification of this syndrome can be a diagnostic dilemma and is frequently made by exclusion. The most characteristic symptoms are postprandial epigastric pain, eructation, fullness, and voluminous vomiting. The symptoms are caused by compression of the third portion of the duodenum against the posterior structures by a narrow-angled SMA. When nonsurgical management is not possible or the problem is refractory, surgical intervention is necessary. We report a case of SMA syndrome in a patient without a history of rapid weight loss. The patient complained of early satiety, nausea, and vomiting of partially digested food worsening over 2 years. Diagnostic evaluation revealed compression of the third portion of the duodenum by the SMA with resultant proximal dilatation. The patient successfully had duodenojejunal anastomosis.

Inhibition of LPS-induced NFkappaB activation by a glucan ligand involves down-regulation of IKKbeta kinase activity and altered phosphorylation and degradation of IkappaBalpha.

Growing evidence supports the role of transcription factor activation in the pathophysiology of inflammatory disorders, sepsis, ARDS, SIRS, and shock. Kinase mediated phosphorylation of IkappaBalpha is a crucial step in the NFkappaB activation pathway. We investigated IKBalpha phosphorylation in murine liver and lung extracts after cecal ligation and puncture (CLP) in the presence and absence of a glucan ligand. ICR mice were subjected to CLP. Unoperated and sham-operated mice served as the controls. Glucan phosphate (50 mg/kg) was administered 1 h before or 15 min after CLP. CLP increased hepatic and pulmonary levels of phospho-IkappaBalpha by 48-192%. Pre- or post-treatment with glucan phosphate decreased (P < 0.05) tissue phospho-IkappaBalpha levels in CLP mice. Phospho-IkappaBalpha in the glucan-CLP group were not significantly different from the unoperated controls. To investigate mechanisms we examined IKKbeta kinase activity, IkappaBalpha phosphorylation and degradation, and NFkappaB activity in a murine macrophage cell line, J774a.1, treated with LPS (1 microg/mL) and/or glucan phosphate (1 microg/mL) for up to 120 min. The glucan ligand blunted LPS-induced IKKbeta kinase activity, phosphorylation and degradation of IkappaBalpha, and NFkappaB nuclear binding activity. The data indicate that one mechanism by which (1-->3)-beta-D-glucan may alter the response to endotoxin or polymicrobial sepsis involves modulation of IKK3 kinase activity with subsequent decreases in IkappaBalpha phosphorylation and NFkappaB activation.

The influence of glucan polymer structure and solution conformation on binding to (1-->3)-beta-D-glucan receptors in a human monocyte-like cell line.

Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>>>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.

Symmetrical peripheral gangrene: a new presentation of an old disease.

This report concerns two cases and a review of the literature on the subject of symmetrical peripheral gangrene. Symmetrical peripheral gangrene is defined as symmetrical distal ischemic damage in two or more sites in the absence of major vascular occlusive disease. It occurs in patients who are septic and have disseminated intravascular coagulation and in nonseptic patients who have cardiogenic or hypovolemic shock. The syndrome is devastating and rare, and controlled studies of its etiology and management are lacking. Recommendations are presented for its prevention and treatment. Cooperative multicenter studies may be necessary to obtain valid data about its prevention and management.

Adenosine prevents activation of transcription factor NF-kappa B and enhances activator protein-1 binding activity in ischemic rat heart.

BACKGROUND: Adenosine prevents myocardial TNF-alpha production induced by ischemia/reperfusion, but the mechanisms are poorly understood. Transcription factors NF-kappa B and AP-1 have been implicated in the regulation of a variety of inducible gene expressions in response to oxidative stress and cellular defense. The effects of adenosine on NF-kappa B and AP-1 activation have not been clearly defined. This study demonstrated differential effects of adenosine on NF-kappa B and AP-1 nuclear binding activity in ischemic myocardium. METHODS: Isolated working rat hearts were subjected to 0, 1, 2, 3, 4, 5, 7.5, 10, 15, and 30 minutes of ischemia, with 4 to 6 hearts for each time point with and without adenosine (100 mumol/L). NF-kappa B and AP-1 binding activity in the nucleus were analyzed by electrophoretic mobility shift assay (EMSA). I kappa B alpha levels in the cytoplasm were measured by Western blot analysis. TNF-alpha mRNA levels were determined by RT-PCR. RESULTS: NF-kappa B binding activity in the nucleus significantly increased after 4 minutes of ischemia and remained to 30 minutes. The levels of I kappa B alpha protein in the cytoplasm markedly decreased after 4, 5, 7.5, and 10 minutes of ischemia. TNF-alpha mRNA levels peaked after 10 minutes of ischemia. AP-1 DNA binding activity was induced and persisted during all ischemic periods. Adenosine significantly inhibited NK-kappa B binding activity in the nucleus, markedly prevented the loss of I kappa B alpha proteins from the cytoplasm, and concomitantly down-regulated TNF-alpha mRNA expression, but enhanced AP-1 binding activity in the nucleus of ischemic myocardium. CONCLUSIONS: Adenosine modulation of NF-kappa B activation may be the cellular molecular mechanism of down-regulation of TNF-alpha mRNA expression. The cardioprotective properties of adenosine may be involved in the differential modulation of NF-kappa B and AP-1 activation during myocardial ischemia.

Nuclear factor kappaB activation in acute appendicitis: a molecular marker for extent of disease?

Nuclear factor-kappaB (NF-kappaB) has been demonstrated to regulate the transcription of target genes and stimulate inflammatory cytokine responses in a variety of inflammatory diseases. Preliminary studies have demonstrated that NF-kappaB is activated early in acute inflammation and sepsis and may serve as an indicator of clinical severity. The present study was designed to evaluate the degree of activation of NF-kappaB in patients with acute appendicitis and correlate activation with clinical extent of disease. Ten patients with acute appendicitis and five control patients (elective inguinal hernia repair) were evaluated by assaying NF-kappaB activity preoperatively and 12 to 18 hours postoperatively. Assaying of NF-kappaB was determined by binding activity for consensus probes in nuclear extracts from peripheral mixed white blood cells obtained by venous puncture. The bands of NF-kappaB activity from gel electrophoresis were quantified with a phosphor imager and reported as units of integrated intensity. The preoperative NF-kappaB activity was increased in all patients with appendicitis versus the controls [mean 151 (range 97-189) vs mean 50.3 (range 13.7-77); P < 0.0001]. The increased NF-kappaB activity also correlated with length of time of symptoms before operation. The patients who were symptomatic for less than 24 hours had an average NF-kappaB value of 103 (range 97-105) versus 171.4 (range 152-189) (P < 0.0001) in those who were symptomatic 24 or more hours. The NF-kappaB activity did not correlate with the white blood cell count. Postoperative NF-kappaB binding activity in the appendicitis patients dropped to minimal levels (mean 50.3), even lower than the control patients' baseline values (mean 55.6). Control patients demonstrated low baseline values preoperatively and a slight rise postoperatively [mean 50.3 (range 13.7-77) vs mean 100 (range 45-186)]. We conclude the following: (1) NF-kappaB binding activity is elevated in patients with acute appendicitis and correlates with symptoms longer than 24 hours. (2) This increased activity returns to baseline values within 18 hours after appendectomy. (3) Molecular indicators of inflammation may have a role in both staging surgical inflammatory conditions and predicting ultimate outcome.

Early activation of pulmonary nuclear factor kappaB and nuclear factor interleukin-6 in polymicrobial sepsis.

BACKGROUND: Transcription factor activation may be a pivotal step in the pathophysiology of sepsis syndrome and adult respiratory distress syndrome. This study investigated the activation of lung nuclear factor kappaB (NFkappaB) and nuclear factor interleukin-6 (NF-IL6) and how they correlate to proinflammatory cytokine expression and mortality in a murine model of cecal ligation and puncture (CLP). METHODS: Polymicrobial sepsis was induced by CLP. Transcription factor activation was assessed at 0, 1, 2, 3, 4, 5, 6, 8, and 24 hours after CLP by the electrophoretic mobility-shift assay. Lung cytokine mRNA levels were established by reverse transcriptase-polymerase chain reaction. RESULTS: CLP induced pulmonary NFkappaB activation at 3, 4, and 8 hours (p < 0.05). Lung NFkappaB activation peaked at 3 hours (533% vs. no surgery, 2,900% vs. sham treatment) after CLP. Supershift analysis revealed a predominance of p50 subunits in the lung nuclear extracts of septic mice 3 hours after CLP, indicating the presence of p50 homodimer. In contrast, liver nuclear extracts from septic mice indicated the presence of both p65 and p50 subunits at 3 hours. Lung NF-IL6 activation (p < 0.05) was observed at 4 hours (649% vs. no surgery, 296% vs. sham treatment) and 6 hours after CLP. Lung tumor necrosis factor-alpha mRNA levels were increased (p < 0.05) at all time intervals after CLP. Lung IL-6 mRNA levels were increased at 3, 6, and 8 hours after CLP. CONCLUSION: Early activation of lung NFkappaB and NF-IL6 and lung cytokine mRNA expression correlated with mortality in polymicrobial sepsis. Although IL-6 mRNA levels correlated with NFkappaB and NF-IL6 activation, tumor necrosis factor-alpha mRNA levels did not, in that they preceded transcription factor activation. These data suggest a potential role for NFkappaB and NF-IL6 activation in the initiation and propagation of acute lung injury.

Early activation of transcription factor NF-kappaB during ischemia in perfused rat heart.

The transcription factor nuclear factor kappaB (NF-kappaB) regulates multiple immediate-early gene expressions involved in immune and inflammatory responses and cellular defenses. Ischemia-reperfusion induces many immediate-early gene expressions, but little is known about the NF-kappaB activation in myocardium during ischemia and reperfusion. This study demonstrated that ischemia alone rapidly induced NF-kappaB activation in the myocardium of isolated working rat hearts. Electrophoretic mobility shift assay showed that NF-kappaB binding activity significantly increased in the nucleus after 5 min of ischemia and remained elevated for up to 30 min. Western blot analysis suggested that the levels of inhibitory IkappaBalpha protein in the cytoplasm became markedly decreased at 4, 5, 7.5, and 10 min of ischemia but were gradually restored following 10 min of ischemia. Reduction of IkappaBalpha protein in the cytoplasm by ischemia resulted in NF-kappaB translocation to the nucleus. Northern blot hybridization showed that IkappaBalpha mRNA levels were not significantly elevated during myocardial ischemia. Pyrrolidine dithiocarbamate, an antioxidant, significantly inhibited the loss of IkappaBalpha protein from the cytoplasm and prevented NF-kappaB binding activity in the nucleus. Reperfusion following short periods of ischemia augmented NF-kappaB binding activity in the nucleus induced by ischemia. The results suggest that early activation of NF-kappaB induced by ischemia in the myocardium could be a signal mechanism for controlling and regulating immediate-early gene expression during ischemia-reperfusion.

Ligand binding to the (1 --> 3)-beta-D-glucan receptor stimulates NFkappaB activation, but not apoptosis in U937 cells.

Recent data suggest that sepsis stimulates macrophage apoptosis (Ao) with subsequent induction of macrophage dysfunction. Nuclear factor-kappaB (NFkappaB) activation has been linked to Ao in either a pro- or antiapoptotic role. Glucans are biological response modifiers which exert antisepsis activity. This investigation examined the effect of (1-3)-beta-D-glucan receptor binding by a high affinity ligand on Ao and NFkappaB activation in U937 cells in the presence or absence of LPS. A high affinity glucan ligand (IC50 = 23 nM) activated NFkappaB, but did not induce Ao or significantly alter LPS induced U937 Ao. These data indicate that: i) modulation of the macrophage (1-3)-beta-D-glucan receptor stimulates NFkappaB; ii) does not induce Ao or significantly diminish LPS induced Ao and iii) activation of the U937 FAS receptor does not alter the relative Ao responses in glucan and LPS treated cells.

Therapeutic modification of nuclear factor kappa B binding activity and tumor necrosis factor-alpha gene expression during acute biliary pancreatitis.

The role of cytokines has been well documented in the pathogenesis of acute pancreatitis. Antibodies against specific cytokines have been used to treat pancreatitis, with mixed results. The transcription factor nuclear factor (NF)-kappa B is a pleiotropic regulator of many genes involved in stress and inflammatory responses. The aim of this study was to prevent the NF-kappa B binding activity and tumor necrosis factor (TNF)-alpha gene overexpression as a possible therapeutic intervention for acute pancreatitis. Reversible acute biliary pancreatitis was induced in male Sprague Dawley rats as established in this laboratory. The animals were sacrificed at 0, 5, 15, 30 min and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the induction of pancreatitis. NF-kappa B binding activity was determined by electrophoretic mobility shift assay, and TNF-alpha gene expression was assayed by reverse transcription-PCR. NF-kappa B binding activity was markedly higher around 4 hours and persisted up to 24 hours after pancreatitis induction in animals with acute pancreatitis, whereas TNF-alpha mRNA levels peaked at 24 hours. When amobarbital (to block NF-kappa B activation) was given (60 mg/kg body weight, I.P.) 3 hours before induction of pancreatitis, the activation of NF-kappa B and the overexpression of TNF-alpha gene was prevented, with significantly decreased severity of pancreatitis as assessed by amylase and clinical recovery. We conclude that 1) preventing the activation of NF-kappa B eliminates the induced overexpression of inflammatory cytokines (TNF-alpha) in acute pancreatitis, 2) such intervention correlates with clinical improvement in pancreatitis, and 3) this genetic modification offers a possible therapeutic intervention in acute pancreatitis.

Delayed ulcer recurrence after gastric resection: a new postgastrectomy syndrome?

Recurrent ulceration following gastrectomy for peptic ulcer disease typically occurs within the first several years postoperatively. Since 1990, we have managed 20 patients who had undergone previous gastrectomy for peptic ulcer and developed ulcer recurrence more than 10 years postoperatively. Mean age at recurrence was 64 years, and the average time from original surgery to recurrent ulceration was 21 years (range, 10-36 years). All patients had undergone vagotomy and antrectomy (17 patients) or subtotal gastrectomy (3 patients). Presenting symptoms included gastric outlet obstruction (70%) and bezoar formation (60%). Endoscopic findings in this group of patients included a stenotic gastric outlet (70%) and marginal ulcerations (80%). Thirteen of 15 patients tested (87%) were Helicobacter pylori positive. Reoperation included partial resection of the gastric pouch and exploration for persistent vagus nerve. Twelve patients underwent Roux-en-Y reconstruction, whereas eight patients had Bilroth II reconstruction. Three of the latter group also had Braun enteroenterostomy performed. Good to excellent clinical results were obtained in 80 per cent of patients. The four patients with poor outcomes shared the following characteristics: 1) H. pylori-positive status, 2) presence of a preoperative bezoar, 3) Roux-en-Y reconstruction. Our current approach is to avoid Roux-en-Y construction in favor of Braun enteroenterostomy. Further prospective analysis of long-term postgastrectomy patients is needed to determine whether this clinical picture represents a new postgastrectomy syndrome.

The application of various protic acids in the extraction of (1-->3)-beta-D-glucan from Saccharomyces cerevisiae.

Glucans are (1-->3)-beta-linked glucose polymers which have immune-stimulating capability. The extraction of water-insoluble (1-->3)-beta-D-glucan form Saccharomyces cerevisiae employs hydrochloric acid. Hydrochloric acid is difficult to employ in the large-scale pharmaceutical extraction of glucans due to its corrosive nature and toxicity. To address these concerns, we determined whether acetic, formic or phosphoric acid can be substituted for hydrochloric acid in the process for the isolation of (1-->3)-beta-D-glucan. The resulting microparticulate glucans were employed as the starting material for the production of (1-->3)-beta-D-glucan phosphate. 13C NMR analysis of the glucan phosphates derived from the acetic, formic or phosphoric acid-extracted microparticulate glucan show excellent correspondence to hydrochloric acid extracted glucan and laminarin, a (1-->3)-beta-D-glucan standard, indicating that the primary structure is not altered by the acid used for extraction. Glucan phosphate prepared from hydrochloric acid had a Mw of 7.2 x 10(4) g/mol, rmsz of 17.7 nm, of 1.50 and (eta) of 49.0 mL/g. Glucan phosphate prepared from acetic acid had a primary polymer peak with a Mw of 1.4 x 10(6) g/mol, rmsz of 23.6 nm, I of 1.93 and (eta) of 62.4 mL/g. Glucan phosphate prepared from formic acid had a main polymer peak with a Mw of 1.2 x 10(6) g/mol, rmsz 27.1 nm, I of 1.56 and (eta) of 89.0 mL/g. Glucan phosphate prepared from phosphoric acid had a primary polymer peak with a Mw of 6.6 x 10(5) g/mol, rmsz of 32.3 nm, I of 2.70 and (eta) of 91.3 mL/g. These data indicate that the molecular mass, size, polydispersity and intrinsic viscosity of the glucan phosphate obtained is influenced by the pKa of protic acid employed to extract the microparticulate glucan. However, the primary structure and side-chain branching are not substantially altered regardless of the acid employed.

Effect of macrophage stimulation on collagen biosynthesis in the healing wound.

Immunomodulators that enhance macrophage function have been shown to be beneficial in a number of wound-healing models in humans and in experimental animals. The exact mechanism of this improved healing is unclear. To assess the role of collagen biosynthesis, the immunomodulator glucan phosphate was utilized in two murine models of wound healing, i.e., colon anastomosis and full-thickness skin incision. Tensile strength was evaluated using computer-assisted constant velocity tensiometry. Collagen biosynthesis was determined by assaying hydroxyproline content of wound hydrolysates by N-(9-fluorenyl)methoxycarbonyl/o-phthalaldehyde high-performance liquid chromatography. Experimental animals were treated with (1-3)-beta-D-glucan phosphate (250 mg/kg) intravenously 24 hours prior to colon anastomosis or skin incision. A second dose of glucan phosphate was given immediately postoperatively. Control animals received dextrose and water (5% w/v) intravenously. Tensile strength and hydroxyproline content were measured on postoperative Day 3. In the skin wound model, glucan phosphate treatment increased (P < 0.05) tensile strength by 42 per cent (342.5 +/- 12.2 vs 241.8 +/- 4.8 g), and hydroxyproline content was increased by 23.5 per cent (242.0 +/- 14.4 vs 196.8 +/- 10.5 pmol/microg; P < 0.05). In the glucan phosphate group, colon tensile strength was significantly (P < 0.05) increased by 34 per cent (34.2 +/- 2.3 g vs 45.8 +/- 2.1 g), and hydroxyproline content was increased by 7 per cent (47.45 +/- 3.31 vs 44.34 +/- 3.74 pmol/microg). These data indicate that macrophage modulation with glucan phosphate will increase tensile strength in experimental colon and skin wounds. In addition, we observed a positive correlation between glucan phosphate treatment, wound tensile strength, and collagen biosynthesis.

A new animal model of reversible acute pancreatitis.

Numerous animal models of acute pancreatitis are utilized to assess pathophysiologic events and to evaluate therapeutic options. However, none of the small animal models simulates reversible biliary pancreatitis with long-term follow-up (weeks). The present study was designed to create a reversible model of acute biliary pancreatitis in small experimental animals. Male Sprague-Dawley rats were subjected to laparotomy, and the common bile duct was dissected free at its junction to the duodenum. Experimental animals had a polypropylene tie occluder passed around the common bile duct and brought out through a separate stab wound in the abdominal wall. The duct was occluded for 24 hr; the blockage was then relieved and the tie withdrawn from the animal. Sham-operative animals had similar surgical procedures but without the occluder. Serum amylase values on Days 1 and 2 following surgery were significantly increased in the experimental group, but were not different from those of control animals on Day 3 or 4, suggesting reversibility of this biliary pancreatitis model. Likewise, serum bilirubin levels were increased in the experimental group on Days 1 and 2. Histologic analysis revealed edema, zymogen degranulation, inflammatory infiltration, vacuolization of acinar cells, and focal areas of fat and parenchymal necrosis in the experimental group. Only mild edema was observed in the sham-operative controls due to surgical manipulation. Pancreatic tissues obtained at 1 week postinduction of pancreatitis showed near total destruction of the architecture and dissolution of zymogen granules; in contrast, histology at the 3rd week showed almost normal-appearing pancreas with return of zymogen granules, suggesting recovery from the acute pancreatitis. This reproducible and reversible model of acute pancreatitis in the rat will provide for further studies in the pathogenesis of pancreatitis and its therapeutic interventions.

The beneficial effect of enhanced macrophage function on the healing of bowel anastomoses.

Inadequate healing and subsequent leakage of bowel anastomoses are serious postoperative complications in abdominal surgery. Previous studies have demonstrated the macrophage to be a key cell in the physiology of wound healing. The current study was undertaken to evaluate the effects of enhanced macrophage function on the healing of bowel anastomoses. Sprague-Dawley rats (250 gm) underwent laparotomy and jejunojejunostomy following IV treatment with glucan (100 mg per kg), a potent macrophage stimulant, or 5 per cent dextrose 24 hours before surgery and again on the day of surgery. Animals were killed and the anastomoses underwent wound tensiometry on Day 3 using a computer-assisted constant velocity tensiometer. The glucan treated animals had a significantly greater anastomotic breaking strength (88.5 gm +/- 10.7 versus 45.45 gm +/- 5.1) (P < 0.01). Formalin fixation increased the breaking strength of the untreated anastomosis but not of the treated anastomosis (92.9 gm +/- 11.77 versus 92.3 +/- 12.44). Analysis of macrophage supernatant for the growth factors epidermal growth factor (EGF), platelet derived growth factor (PDGF), and transforming growth factor-beta (TGF-beta) was accomplished by immunoblot assay. Results indicated no difference in the presence of EGF in the stimulated and unstimulated macrophage supernatants. PDGF and TGF-beta were decreased in the stimulated macrophage supernatants. We conclude that 1) Enhanced macrophage function had a beneficial effect on the early tensile strength of bowel anastomoses. 2) Effects of the activated macrophage on bowel anastomoses may not be related to secretion of conventional growth factors. 3) Immunopharmacologic agents that enhance macrophage function may be an important adjunct to surgical therapy requiring bowel anastomosis.

The lost laparoscopic stone. Potential for long-term complications.

Intraperitoneal gallstones left behind at laparoscopic cholecystectomy are not uncommon. Such stones have previously been thought to be harmless. We report three instances of delayed intra-abdominal infection and/or inflammation related to these misplaced gallstones. All three patients presented months postoperatively with vague abdominal complaints. Computed tomography revealed inflammatory foci involving intraperitoneal gallstones. All patients required percutaneous or operative drainage of the collections. Every effort should be made to locate and remove "spilled" gallstones at the time of laparoscopic cholecystectomy.

Third place winner of the Conrad Jobst Award in the gold medal paper competition. Prevention of spinal cord dysfunction in a new model of spinal cord ischemia.

Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)