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PURPOSE: To determine the diagnostic performance of bedside assessment of end-tidal alveolar dead space fraction (ADSF) for pulmonary embolism (PE) and whether the use of additional ADSF assessment following D-dimer assay can improve the diagnostic accuracy in suspected PE patients in the emergency department. METHODS: A prospective observational study of 112 consecutive adult patients suspected of PE of whom 102 were eligible for analysis. ADSF was calculated using arterial carbon dioxide and end-tidal carbon dioxide. An ADSF less than 0.2 was considered normal. RESULTS: PE was confirmed in 11 (10.8%) of 102 patients. D-dimer assay alone as a reference standard test for PE had a sensitivity of 100%, specificity of 38.5% and false negativity of 0%. Area under the receiver-operator characteristic curve for the diagnosis of PE using ADSF values alone was 0.894, Sensitivity, specificity and false negativity for the combined results of a positive D-dimer test and abnormal ADSF were 100%, 78.0% and 0% for the presence of PE, respectively. Of 65 patients with a low or intermediate clinical probability and a positive D-dimer assay, 36 (55.4%) patients displayed normal ADSF and had no PE. CONCLUSIONS: By itself ADSF assessment performed well in diagnosis of PE. The combined result of a positive D-dimer and abnormal ADSF increased the specificity for diagnosing PE compared with the D-dimer test alone. The use of additional bedside ADSF assessment following a positive D-dimer test may reduce the need for further imaging studies to detect PE in patients with a low or intermediate clinical probability. [ABSTRACT FROM AUTHOR]

Objective: To compare outcome parameters for good-risk patients with classic signs, symptoms, and laboratory and abdominal imaging features of cholecystolithiasis and choledocholithiasis randomized to either laparoscopic cholecystectomy plus laparoscopic common bile duct exploration (LC+LCBDE) or endoscopic retrograde cholangiopancreatography sphincterotomy plus laparoscopic cholecystectomy (ERCP/S+LC)., Design: Our study was a prospective trial conducted following written informed consent, with randomization by the serially numbered, opaque envelope technique., Setting: Our institution is an academic teaching hospital and the central receiving and trauma center for the City and County of San Francisco, California., Patients: We randomized 122 patients (American Society of Anesthesiologists grade 1 or 2) meeting entry criteria. Ten of these patients, excluded from outcome analysis, were protocol violators having signed out of the hospital against medical advice before 1 or both procedures were completed., Interventions: Treatment was preoperative ERCP/S followed by LC, or LC+LCBDE., Main Outcome Measures: The primary outcome measure was efficacy of stone clearance from the common bile duct. Secondary end points were length of hospital stay, cost of index hospitalization, professional fees, hospital charges, morbidity and mortality, and patient acceptance and quality of life scores., Results: The baseline characteristics of the 2 randomized groups were similar. Efficacy of stone clearance was likewise equivalent for both groups. The time from first procedure to discharge was significantly shorter for LC+LCBDE (mean [SD], 55 [45] hours vs 98 [83] hours; P < .001). Hospital service and total charges for index hospitalization were likewise lower for LC+LCBDE, but the differences were not statistically significant. The professional fee charges for LC+LCBDE were significantly lower than those for ERCP/S+LC (median [SD], $4820 [1637] vs $6139 [1583]; P < .001). Patient acceptance and quality of life scores were equivalent for both groups., Conclusions: Both ERCP/S+LC and LC+LCBDE were highly effective in detecting and removing common bile duct stones and were equivalent in overall cost and patient acceptance. However, the overall duration of hospitalization was shorter and physician fees lower for LC+LCBDE., Trial Registration: clinicaltrials.gov Identifier: NCT00807729.

Objective: To examine whether case managers affect patient evaluation/treatment/outcome and staffing requirements during Multiple Casualty Incidents (MCIs)., Summary Background Data: Multiple patient relocations during MCIs may contribute to chaos. One hospital changed its MCI patient relocation policy during a wave of MCIs; rather than transfer patients from one medical team to another in each location, patients were assigned case-managers +/- teams who accompanied them throughout the diagnostic/treatment cascade until definitive placement., Methods: MCI data (n = 17, 2001-2006) were taken from the hospital database which is updated by registrars in real-time. ISSs were calculated retrospectively. Matched events before (n = 5)/after (n = 3) the change yielded data on staff utilization. Semi-structured interviews were conducted with 26 experienced staff members regarding the effect of the change on patient care., Results: Twelve events occurred before (n = 379 casualties) and 5 occurred after (n = 152 casualties) the change. Event extent/severity, manpower demands and patient mortality remained similar before/after the change. Reductions were observed in: the number of x-rays/patient/1st 24-hour (P < 0.001), time to performance of first chest x-ray (P = 0.015), time from first chest x-ray to arrival at the next diagnostic/treatment location (P = 0.016), time from ED arrival to surgery (P = 0.022) and hospital lengths of stay for critically injured casualties (37.1 +/- 24.7 versus 12 +/- 4.4 days, P = 0.016 for ISS > or = 25). Most interviewees (62%, n = 16) noted improved patient care, communication and documentation., Conclusions: During an MCI, case managers increase surge capacity by improving efficacy (workup/treatment times and use of resources) and may improve patient care via increased personal accountability, continuity of care, and involvement in treatment decisions.

Endovascular stents have had a limited role in the management of trauma and vascular emergencies involving active hemorrhage. We describe a patient with delayed rupture of the infrarenal aorta after intra-abdominal sepsis caused the breakdown of a primary aortic repair. A stent-graft repair was performed, as concomitant injuries did not allow anterior access to the aorta. This report describes the successful endovascular repair of an actively hemorrhaging penetrating abdominal aortic injury. Endovascular approaches to aortic injuries may be valuable in settings where a hostile abdomen precludes traditional open repair.

Background: Bacterial pathogens and their products are potential agents of biological terrorism and biological warfare. These agents can be deployed through simple aerosol delivery systems and thereby cause widespread disease and death., Methods: This report is a review of bacterial species that have been employed for development of biological terrorism, relying on a system for classification of their threat developed by the Centers for Disease Control., Results: Physicians must understand how to recognize early signs and symptoms caused by bacterial agents. Clinical findings often seen on presentation are emphasized along with a summary of therapeutic approaches., Conclusions: Initiation of immediate therapy and supportive care provides the best chance for survival from these potentially lethal and devastating infections. A high index of suspicion must be maintained, especially in the setting of a sudden influx of cases with what are often relatively nonspecific symptoms.

The spiral computed tomography (CT) scan has made the diagnosis of traumatic injury increasingly rapid and accurate, especially in cases of solid parenchymal organ injury that follows blunt abdominal trauma. Nonetheless, this valuable method of diagnosis can be confounded when anatomical variances are encountered in the setting of concomitant associated injuries. We present here a case where a congenitally bi-lobed spleen was diagnosed by CT scan as an apparent high-grade splenic laceration, prompting emergent laparotomy.

aparoscopic adrenalectomy is the standard for most surgical adrenal diseases. The aim of this study was to evaluate the safety and effectiveness of laparoscopic adrenalectomy for patients with pheochromocytoma. The medical records of 39 consecutive patients who underwent laparoscopic adrenalectomy for pheochromocytomas from 1994 to 2000 at the University of California-San Francisco were reviewed. Three groups of patients were identified. The first group comprised 17 patients with classic symptoms and signs of pheochromocytoma. The second group comprised 17 patients who had minimal symptoms and incidentally discovered pheochromocytoma (i.e., "incidentaloma"), almost half of whom inappropriately underwent fine-needle biopsies before diagnosis. The third group consisted of 5 patients who had acute hypertensive crises and required intensive preoperative preparation. The mean age of the 22 men and 17 women was 46 years (range 20-84 years), and the mean adrenal tumor size was 4.8 cm (range 2-12 cm). A total of 43 laparoscopic adrenalectomies were performed for 35 patients with unilateral tumors and 4 patients with bilateral tumors. The retroperitoneal approach was used in four patients and the lateral transabdominal approach in the remaining patients without conversion to an open operation. There were no intraoperative complications or mortality. The mean duration of hospitalization was 1.7 days. In conclusion, patients with pheochromocytoma have a wide spectrum of presentations, from minimal symptoms to hypertensive crises. When evaluating an incidentaloma, pheochromocytoma should be excluded by metabolic testing, not by needle biopsy. Laparoscopic adrenalectomy is the preferred surgical approach for patients with pheochromocytoma because it is safe and efficacious.

Acute torsion of the small bowel mesentery is a diagnostically challenging cause of acute abdominal pain, which most commonly afflicts pediatric patients with midgut malrotation. We describe a case of mesenteric torsion in an adult patient that had manifested as acute abdominal pain. The patient had a remote history of prior abdominal surgery, presenting on multiple occasions with undiagnosed acute intermittent abdominal pain. Diagnosis of mesenteric torsion was made by contrast enhanced CT and the ailment was successfully treated with laparoscopic surgery without recurrence.

Background: The heat shock response entails the increased expression of heat shock proteins (hsp) which are capable of protecting cells from subsequent metabolic insults. Here we are interested in determining whether activation of the heat shock response might affect polymorphonuclear leukocyte (PMN) function and/or longevity., Methods: Freshly isolated human PMN were either left at 37 degrees C or subjected to a 43 degrees C heat shock treatment (60 min) and subsequently returned to 37 degrees C. During the course of the recovery period a number of parameters were examined for the control and heat shock-treated neutrophils: the relative expression of the highly stress-inducible hsp72; respiratory burst activity as measured by intracellular peroxidation in response to phorbol ester addition; cell-surface expression of CD16; and finally, the extent of apoptosis as determined by both annexin V staining and nuclear propidium iodide staining., Results: Heat shock treatment resulted in a progressive increase in hsp72 production, peaking at 8 h following return of the cells to 37 degrees C. Net intracellular oxidant production was diminished by 46% immediately following the heat shock treatment and deteriorated even further over the next 4 h. Finally, a significant early increase in the rate of apoptosis was observed in the cells subjected to the hyperthermic treatment. This increase in the heat-induced rate of apoptosis was associated with a marked reduction in cell-surface CD16 levels., Conclusions: By decreasing PMN oxidative functions and by accelerating their apoptotic demise, it would appear that heat shock is anti-inflammatory and not cytoprotective for PMN., (Copyright 1999 Academic Press.)

Hypothesis: That the clinical presentations, biochemical profiles, and surgical outcomes of patients treated with laparoscopic vs open adrenalectomy for primary hyperaldosteronism are different. DESIGN, SETTINGS, PATIENTS, AND INTERVENTIONS: The medical records of 80 patients with primary hyperaldosteronism who underwent open adrenalectomy between 1975 and 1986 or laparoscopic adrenalectomy between 1993 and 1998 at the University of California-San Francisco were reviewed by a single unblinded researcher (W.T.S.)., Main Outcome Measures: Severity of hypertension and hypokalemia at diagnosis, their improvement after adrenalectomy, and operative complications., Results: Thirty-eight patients underwent open adrenalectomy and 42 patients underwent laparoscopic adrenalectomy. The patients who underwent open adrenalectomy had documented hypertension for a median of 5 years before surgery; all had diastolic blood pressures greater than 100 mm Hg. Laparoscopically treated patients had documented hypertension for a median of 2.5 years preoperatively, and 20 (48%) had diastolic blood pressures greater than 100 mm Hg. The median preoperative serum potassium levels for the open and laparoscopic groups were 2.6 mmol/L and 3.3 mmol/L, respectively; the mean serum aldosterone levels were 1.47 nmol/L and 1.30 nmol/L. Thirty-two (84%) of the 38 patients who underwent open surgery and 41 (98%) of the 42 patients treated laparoscopically had adrenal adenomas. The sensitivity of preoperative computed tomographic scanning for adenomas was 83% for the patients treated with open adrenalectomy and 93% for those treated laparoscopically. There were 4 postoperative complications in the open surgery group and none in the laparoscopic group. Postoperatively, 30(81%) of 37 patients (excluding 1 patient who died of adrenocortical carcinoma) in the open surgery group and 37 (88%) of 42 patients treated laparoscopically were normotensive. Post-operative values were 3.6 to 5.0 of serum potassium per liter and 3.5 to 4.9 of serum potassium per liter in the open and laparoscopic groups, respectively., Conclusions: Patients who are treated with laparoscopic adrenalectomy for primary hyperaldosteronism are being referred with less severe hypertension and hypokalemia than patients formerly treated with open adrenalectomy. Patients treated laparoscopically had fewer postoperative complications and were equally likely to improve in blood pressure and hypokalemia. Laparoscopic adrenalectomy has become the treatment of choice for patients with primary hyperaldosteronism because of lower morbidity.

Objective: To assess factors that might predict serious necrotizing soft tissue infections following illicit drug injection., Design: A retrospective review of a consecutive case series., Setting: An urban municipal hospital., Patients: Thirty patients presenting with cutaneous abscesses resulting from illicit drug injections during a 5-year period. All cases presented clinically with fluctuance, erythema, or induration but required extensive debridement at the time of incision and drainage., Interventions: Operative treatment employed wide incision, routine subfascial examination, and aggressive debridement. Clinical management included broad-spectrum antibiotics, critical care support, and reconstructive procedures., Main Outcome Measures: Mortality, extent of debridement, preoperative vital signs and laboratory values, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, bacteriologic and pathologic test results., Results: Postoperatively, all patients were housed in the intensive care unit for 8.4 +/- 14.5 days. Six patients died (20%). On arrival at the intensive care unit, systolic blood pressure was 80 mm Hg or less in 2 patients, 1 of whom died. White blood cell count on hospital admission was elevated in 27 of 30 patients (mean, 27.2 +/- 15.3 x 10(9)/L) and 2 patients were identified as having human immunodeficiency virus infection. All patients underwent initial surgery less than 24 hours after admission; following debridement, the average wound size was 276 +/- 238 cm2 (range, 15-783 cm2). Five patients required extremity amputation, and all other survivors underwent reconstruction with skin grafts and/or myocutaneous flaps. All but 1 patient were reexamined in the operating room within 12 hours and underwent an average of 3.1 +/- 1.6 operative procedures. Of those wound cultures obtained in the operating room, there was no pattern to the bacteriologic isolates. Seventeen patients had mixed isolates and 11 had single organisms. Pathologic findings in 20 patients included panniculitis (3 patients), necrotizing fasciitis (11 patients), myositis (6 patients), and osteomyelitis (1 patient). We failed to identify any clinical factor, including temperature, heart rate, systolic blood pressure, white blood cell count, base deficit, albumin level, PO2, or APACHE II score that could predict mortality or the requirement for extensive debridement., Conclusions: Parenteral injections of illicit drugs can produce infections that present with signs of simple cutaneous abscess and yet unpredictably become extensive necrotizing soft tissue infections. Treatment requires a high index of suspicion along with an inquisitive operative approach to avoid missing these potentially serious infections.

Having previously reported that septic patients displayed lower levels of monocyte CD14 (endotoxin receptor) as compared to normal individuals, we were interested in the hypothesis that lipopolysaccharide (LPS) modulates levels of monocyte CD14 in vivo. We examined CD14 expression in 13 human volunteers who were given a non-lethal injection of Escherichia coli LPS (4.0 ng/kg). Monocyte CD14 was assayed by direct immunofluorescent determination with appropriate anti-CD14 monoclonal antibodies using flow cytometry. To test for cell responsiveness, monocytes were additionally examined following in vitro stimulation by phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (FMLP). Following LPS infusion, all patients displayed significant monocytopenia and responded with fever and tachycardia. Plasma samples demonstrated elevated levels of TNF alpha. CD14 expression was down-regulated by 52% on monocytes obtained 3 hr following LPS infusion (P < 0.05, vs. pre-LPS levels). Monocytes obtained pre-LPS infusion were down-regulated following in vitro stimulation by PMA to levels 72 +/- 8% and by FMLP to levels 75 +/- 5% of unstimulated control cells. In contrast, monocytes obtained 3 hr post-LPS infusion failed to respond to PMA or FMLP with significant down-regulation. LPS down-regulated CD14 expression on monocytes in vivo and LPS also blunted the ability of monocytes to respond to other stimuli. We conclude that LPS desensitizes monocytes to itself and thereby renders an immunodepressive effect on these cells.

Objective: To compare the lateral transabdominal and posterior retroperitoneal laparoscopic methods for performing adrenalectomy., Design: Nonrandomized., Setting: Hospitals affiliated with the University of California, San Francisco., Patients: Thirty-six patients (15 men and 21 women), aged 5 to 78 years (mean age, 49 years), were treated for the following conditions: aldosteronoma, 18 patients; pheochromocytoma, 4 patients; Cushing syndrome, 6 patients; androgen-secreting tumor, 1 patient; nonfunctioning adenoma, 3 patients; adrenal hemorrhage, 1 patient; metastatic neoplasm, 2 patients; and myelolipoma, 1 patient., Interventions: Twenty-three lateral and 14 posterior laparoscopic adrenalectomies., Main Outcome Measures: Success rate, operating time, complications, and length of hospital stay., Results: The tumors, which ranged in size from 1 to 13 cm (mean, 4.2 cm; median, 2.5 cm), were all successfully resected laparoscopically. All 8 tumors larger than 6 cm were resected by the lateral approach. One critically ill patient died. No patient required blood transfusions or conversion to laparotomy. Mean operating time was 3.8 hours vs 3.4 hours (median, 3.5 hours vs 3 hours) and mean hospital stay was 2.2 days vs 1.5 days (median, 2 days vs 1 day) for the lateral and posterior approaches, respectively. All patients without concomitant procedures were ready to be discharged within 48 hours., Conclusions: Both approaches were effective and safe. We prefer the lateral approach for tumors larger than 6 cm and the posterior approach for bilateral tumors.

Unexpected sudden death is a common event in otherwise healthy epileptics, though its etiology has remained unclear. Many authors have suggested cardiac arrhythmias as the cause, and limited data in humans and animal studies have supported this. However, autopsy series in humans have shown pulmonary edema, a phenomenon not compatible with a sudden arrhythmic death, as a possible cause. We developed a model of status epilepticus in unanesthetized, chronically instrumented sheep in which sudden death and pulmonary edema occur. Catecholamine levels and seizure type and duration did not differ between animals dying suddenly and those surviving. Benign arrhythmias were generated in all animals; in no case did an arrhythmia account for the death of an animal. Striking hypoventilation was demonstrated in the sudden death group but not in the surviving animals. Differences in peak left atrial and pulmonary artery pressures, and in extravascular lung water were also demonstrated; pulmonary edema did not account for the demise of the sudden death animals. Thus, our model of epileptic sudden death supports a role of central hypoventilation in the etiology of sudden unexpected death and confirms the association with pulmonary edema. The importance of arrhythmia in its pathogenesis is not confirmed.

Marked elevation of transforming growth factor-beta 1 (TGF-beta 1) has been demonstrated clinically following injury and in sepsis. While alterations in the monocyte binding site (CD14) for the lipopolysaccharide (LPS)-lipopolysaccharide binding protein (LBP) complex have been noted with exposure to LPS, immune complexes, gamma-interferon, and IL-4, it is not known whether TGF-beta 1 can alter CD14 expression. To study the effect of TGF-beta 1 on monocyte CD14 expression, human leukocytes were isolated from healthy donors with discontinuous gradient centrifugation and incubated at 37 degrees C for 2 and 24 hr with increasing doses of purified human platelet TGF-beta 1. Monocytes were immunofluorescently stained with monoclonal antibodies recognizing CD14 and CD16. The cells were analyzed by flow cytometry. At 2 hr, 50 ng/ml TGF-beta 1 significantly lowered CD14 expression (51%, P = 0.043). At 24 hr, there was no significant difference between cells stimulated by TGF-beta 1 and control cells. To confirm that TGF-beta 1 was active at 24 hr, we examined levels of CD16. CD16 expression was increased by 10 ng/ml of TGF-beta 1. These observations suggest that high physiologic concentrations of TGF-beta 1 cause early monocyte suppression of CD14. Thus, CD14 may be marker for the transition of monocytes to macrophages and TGF-beta 1 may be responsible for the down-regulation of CD14 expression observed in monocytes obtained from septic patients.

Objectives: To determine if splenectomy results in an increased risk for perioperative infection when analyzed against splenic repair and to identify factors associated with perioperative infection, respiratory complication, and admission to the intensive care unit following surgery for splenic trauma., Design: Data were collected retrospectively from hospital records and analyzed using stepwise multiple logistic regression., Setting: San Francisco (Calif) General Hospital, an urban level 1 trauma center., Patients: All patients (n = 252) undergoing operation for traumatic splenic injury at San Francisco General Hospital from 1984 through 1990. Patients who died within 24 hours of presentation were excluded from the study., Main Outcome Measures: Perioperative infection, respiratory complications, and admission to the intensive care unit., Results: Infection rates and the types of organisms yielded in cultures were similar between patients who underwent splenectomy and repair. Gram-negative and gram-positive organisms were found in equal numbers, and in no group did encapsulated organisms predominate. Splenectomy had no independent impact on any of the three outcome measures. Total blood transfusion was found to be the only independently significant variable associated with perioperative infection and respiratory complication. Total blood transfusion of more than 2 U and Injury Severity Score of greater than 25 were independently significantly associated with admission to the intensive care unit., Conclusions: The choice between splenectomy and splenic repair does not affect the risk for perioperative infection following injury, whereas blood transfusion significantly increases the risk for perioperative infection, respiratory complication, and admission to the intensive care unit.

The monocyte is a pivotal cell in septic patients that responds to endotoxin with release of inflammatory cytokines. Monocytes display on their surface a receptor (CD14) for complexes formed by endotoxin (lipopolysaccharide, LPS) and a plasma LPS-binding protein (LBP). We compared monocytes obtained from normal controls with those obtained from septic patients for expression of CD14 by flow cytometric analysis of immunofluorescent-stained cells. In normal individuals and patients, 75%-95% of monocytes are CD14 positive (CD14+). Mean fluorescence exhibited by the CD14+ population was measured after maintaining cells at 37 degrees C for 15 minutes and compared with baseline cells held at 4 degrees C (mean fluorescence ratio). All cells increased their CD14 mean fluorescence ratio with warming; however, the level achieved by monocytes obtained from septic patients was on average 78% +/- 8% of control levels (p = 0.014). To further clarify CD14 expression, we examined the effect of Escherichia coli LPS on normal monocytes by comparing monocytes treated in serum-free buffer (no LBP) with monocytes treated in whole blood (containing LBP). The LPS (1.0 ng/mL) incubated with whole blood for 120 minutes generated an increase in CD14+ mean fluorescence compared with buffer. In contrast, phorbol myristate acetate lowered CD14+ mean fluorescence levels. These data indicate that normal monocytes incubated in the presence of ligand (LBP-LPS complexes) increase their expression of CD14, whereas CD14 expression in septic patients is diminished. We conclude that monocytes from septic patients were responsive to other stimuli aside from LPS and that decreased expression of CD14 may indicate a poor prognosis.

Intravenous infusions of endotoxin in sheep cause lung injury characterized by edema due to increased microvascular permeability. Similar increases in pulmonary microvascular permeability are seen in septic patients with the adult respiratory distress syndrome. Since endotoxin-induced lung injury may be mediated by interactions between products of complement activation and polymorphonuclear leukocytes, plasma and lung lymph from six unanesthetized sheep infused with Escherichia coli endotoxin (1.0 micrograms/kg over 30 min) were examined for complement-derived chemotactic activity. By 2-3 hr following infusion of endotoxin, all animals had the increased lung lymph fluid and protein flows characteristic of permeability edema. Preinfusion samples of plasma and lung lymph did not contain chemotactic activity for polymorphonuclear leukocytes. Following infusion of endotoxin, however, significant chemotactic activity was detected in plasma at 0.5-3.5 hr (P less than 0.05) and in lymph at 1.5-6.5 hr (P less than 0.025). The chemotactic activity was heat stable (56 degrees C for 30 min) but was abolished by treatment with antibodies to C5. These data indicate that infusions of endotoxin lead to the generation in plasma, and the appearance in lung lymph, of C5-derived peptides with chemotactic activity for polymorphonuclear leukocytes. C5-derived peptides may account for the pulmonary microvascular leukostasis and endothelial injury that lead to increased permeability edema after infusions of endotoxin.

We studied the effects of reducing total hemolytic complement activity with Naja haje cobra venom factor on the lung injury caused by intravenously infused endotoxin in 5 unanesthetized sheep with lung lymph fistulas. In normal sheep, infusions of lipopolysaccharide W from Escherichia coli (1.0 micrograms/kg) intravenously over 30 min caused increases in protein-rich lung lymph flow as well as the appearance in plasma and lung lymph of complement (C5)-derived chemotactic activity for polymorphonuclear leukocytes. Reduction of total hemolytic complement activity by treatment with Naja haje cobra venom factor (12 to 17 U/kg intraperitoneally) did not prevent the lung injury caused by endotoxin and also did not prevent the appearance in plasma and lung lymph of chemotactic activity. We conclude that although complement appears to be activated following intravenously infused endotoxin in sheep, a completely intact complement system is not necessary for endotoxin-induced lung injury.

Serum specimens from guinea pigs with experimentally induced acute pancreatitis were examined for evidence of protease-antiprotease imbalance and complement catabolism. Pancreatitis was induced in 22 male Hartley guinea pigs by the injection of sodium taurocholate into the pancreatic parenchyma. Only a laparotomy was performed in 6 control animals. In 10 experimental animals that survived for less than 24 hours, there was a significant, early reduction of serum trypsin inhibitory capacity (a measure of antiprotease activity). Levels of total hemolytic complement as well as titers of hemolytic C3 and C4 fell significantly in all experimental animals during the first 24 hours. Factor B activity, however, did not change. Only serum from experimental animals contained chemotactic activity for human polymorphonuclear leukocytes. These findngs indicate that circulating complement components are cleaved during the course of experimental acute pancreatitis. As a consequence, complement-derived peptides are generated that may mediate local and systemic tissue injury.

Samples of serum and plasma obtained from eight patients with acute pancreatitis were examined for the presence of complement-derived chemotactic activity for human PMN. Significant chemotactic activity was found in acute phase serum and plasma samples from five patients. The presence of chemotactic activity was associated with reduced levels of CH50 as well as degradation products of C5 (detected by a new method, i.e., radioimmunoelectrophoresis). The chemotactic activity was heat-stable (56 degrees C for 30 min), inhibitable by treatment with antibodies to human C5, and exhibited an apparent molecular weight of 16,000 (determined by chromatography on Sephadex G-75). These properties are identical with those of chemotactic C5-derived peptides (C5a and/or C5a des Arg). Recently, C5-derived peptides have been implicated as being mediators of acute lung injury (i.e., "shock lung") in some clinical situations. It is intriguing to speculate, therefore, that circulating C5-derived chemotactic peptides may play a role in the pathogenesis of the lung injury observed in some patients during the course of acute pancreatitis.

Monocytes that bear HLA Class II antigens, such as HLA-DR, HLA-DQ, or HLA-DP, are obligatory for many cell-mediated immunological processes. Patients with thermal injury suffer from hypoimmunity and are at risk for developing life-threatening septic episodes. To determine whether an alteration in expression of HLA Class II antigens is involved in the defect, monocytes from the peripheral blood of burn patients and controls were double-stained with anti-Leu-M3 and either anti-HLA-DR, HLA-DQ, or HLA-DP monoclonal antibodies. As analysed by flow cytometry the percentage of Leu-M3+ monocytes from the peripheral blood from patients and controls was the same. The percentage of Leu-M3+ monocytes bearing the HLA Class II antigens and the density of antigen on the monocytes, however, was significantly reduced post-burn compared with controls. In nearly all cases these changes were detected as early as 24 h post-burn before any drug therapy was implemented. In-vivo re-expression of normal levels of HLA Class II coincided with patient recovery. In-vitro exposure of post-burn Leu-M3+ cells to IFN-gamma for 72 h restored HLA Class II expression to control levels. It is possible that the reductions in HLA Class II expression may be involved in the general immunosuppression that follows thermal injury.