Triple-contrast helical CT in penetrating torso trauma: a prospective study to determine peritoneal violation and the need for laparotomy.

OBJECTIVE: A prospective study was performed to determine the usefulness of triple-contrast helical CT in predicting peritoneal violation and the need for laparotomy in the treatment of penetrating torso trauma. SUBJECTS AND METHODS: Triple-contrast helical CT scans were obtained in 104 hemodynamically stable patients with penetrating injuries to the torso (thoracoabdominal region including tangential wounds to the anterior abdomen, flank, back, and pelvis) over a 17-month period. The study group included 54 patients with gunshot wounds and 50 with stab wounds. No patient had a radiographic or clinical indication for immediate laparotomy. A positive finding on CT was defined as evidence of peritoneal violation or injury to the retroperitoneal colon, major vessel, or urinary tract. Patients with a positive CT, except patients with isolated liver injury or free fluid, underwent laparotomy. Patients with a negative finding on CT were initially observed. RESULTS: CT studies were positive in 35 (34%) of 104 patients and negative in 69 (66%) of 104 of patients. Laparotomy was performed in 21 (60%) of 35 patients with positive CT; 19 (86%) of 22 were therapeutic, two (9%) were nontherapeutic, and one (5%) was negative (no injury was found). Nine patients with isolated hepatic injuries were successfully treated without laparotomy. Among patients with a negative CT, 67 (97%) of 69 were treated nonoperatively with success. CT had 100% (19/19) sensitivity, 96% (69/72) specificity, 100% (69/69) negative predictive value, and 97% (101/104) accuracy in predicting the need for laparotomy. CONCLUSION: Triple-contrast helical CT can accurately predict the need for laparotomy and exclude peritoneal violation in penetrating torso trauma including tangential abdominal wounds.

Helical computed tomography of bowel and mesenteric injuries.

BACKGROUND: The role of computed tomography in diagnosing hollow viscus injury after blunt abdominal trauma remains controversial, with previous studies reporting both high accuracy and poor results. This study was performed to determine the diagnostic accuracy of helical computed tomography in detecting bowel and mesenteric injuries after blunt abdominal trauma in a large cohort of patients. METHODS: One hundred fifty patients were admitted to our Level I trauma center over a 4-year period with computed tomographic (CT) scan or surgical diagnosis of bowel or mesenteric injury. CT scan findings were retrospectively graded as negative, nonsurgical, or surgical bowel or mesenteric injury. The CT scan diagnosis was then compared with surgical findings, which were also graded as negative, nonsurgical, or surgical. RESULTS: Computed tomography had an overall sensitivity of 94% in detecting bowel injury and 96% in detecting mesenteric injury. Surgical bowel cases were correctly differentiated in 64 of 74 cases (86%), and surgical mesenteric cases were correctly differentiated from nonsurgical in 57 of 76 cases (75%). CONCLUSION: Helical CT scanning is very accurate in detecting bowel and mesenteric injuries, as well as in determining the need for surgical exploration in bowel injuries. However, it is less accurate in predicting the need for surgical exploration in mesenteric injuries alone.

Using CT to diagnose tracheal rupture.

OBJECTIVE: A retrospective study was performed to assess CT sensitivity for diagnosing tracheal rupture. Intubated cadaver tracheas were examined to assess endotracheal tube balloon overdistention and deformity and to evaluate the relationship of balloon pressures to tracheal injury. MATERIALS AND METHODS: Neck or chest CT scans of 14 patients with tracheal rupture and 41 control trauma patients with pneumomediastinum but without tracheal injury were reviewed and compared to assess the presence and location of extrapulmonary air, whether direct visualization of tracheal wall disruption was possible, the size and shape of endotracheal tube balloon, signs of transtracheal balloon herniation in intubated patients, and the location of the extratracheal endotracheal tube. Intact and experimentally injured cadaver tracheas were used to evaluate tube balloon pressure and configuration. RESULTS: All 14 patients with tracheal rupture had deep cervical air and pneumomediastinum. Overdistention of the tube balloon occurred in 71% (5/7) of the intubated patients, and balloon herniation occurred in 29% (2/7). Direct tracheal injury was seen in 71% (10/14) of the patients as a wall defect (n = 8) or deformity (n = 2). Overall, CT was 85% sensitive for detecting tracheal injury. Patients with tracheal injury had a significantly lower incidence of pneumothorax (p = 0.01) than did the control group. The CT appearance of balloon herniation through defects in the cadaver tracheas closely mimicked those of patients with tracheal injury. The amount of balloon pressure required to rupture the intubated trachea was extremely high and rupture was difficult to obtain. CONCLUSION: CT can reveal tracheal injury and can be used to select trauma patients with pneumomediastinum for bronchoscopy, leading to early confirmation and treatment.

CT findings after embolization for blunt splenic trauma.

PURPOSE: To determine complications after transcatheter embolization for blunt splenic injury as recognized with computed tomography (CT). MATERIALS AND METHODS: From March 1997 to January 2000, 80 patients underwent transcatheter embolization after blunt splenic injury, of whom 53 underwent abdominal CT examination before and after embolization. Preembolization CT scans were reviewed to determine grade of injury, and postembolization CT scans were reviewed to identify complications secondary to embolization. Arteriography results were reviewed to determine findings and method and location of embolization. RESULTS: Splenic infarcts occurred in 63% of patients after proximal embolization and in 100% of patients after distal embolization. Infarcts after distal embolization tend to be larger and occur just distal to the embolization material, whereas infarcts after proximal embolization tend to be smaller, multiple, and located in the periphery. Most infarcts resolved without sequelae. Seven patients developed gas within an infarct or subcapsular fluid collection. Two collections were drained and found to be sterile and one patient had a splenic abscess at laparotomy. CONCLUSIONS: Infarcts are common after splenic embolization. Gas may be present within an infarct after embolization with Gelfoam; however, the presence of air/fluid level is a better predictor of abscess.

CT diagnosis of internal mammary artery injury caused by blunt trauma.

AIM: To describe the computed tomography (CT) findings associated with active bleeding from the internal mammary artery (IMA) in blunt trauma victims and to assess complications related to IMA haemorrhage. MATERIAL AND METHODS: All cases of active IMA haemorrhage identified in blunt trauma patients on admission CT were identified from a trauma radiology data base covering 1990-1999. Computed tomography examinations, operative and medical records were reviewed to ascertain CT findings, complications, and patient outcome. The determination of active bleeding required CT evidence of a central contrast blush of CT density within 10 HU of an adjacent artery surrounded by haematoma. RESULTS: Four patients with CT evidence of active IMA haemorrhage were identified. All cases had surgical confirmation of an IMA source of haemorrhage. There were three patients with unilateral and one patient with bilateral IMA disruption. Three patients exhibited clinical signs of cardiac tamponade related to compression of one or more cardiac chambers by the anterior mediastinal haematoma. Sudden clinical deterioration compatible with tamponade developed in all three patients. CONCLUSION: Early CT recognition of active bleeding within the chest can direct rapid surgical or angiographic intervention. On-going blood loss and, in particular, the threat of cardiac tamponade must be considered with IMA injury.

CT criteria for management of blunt liver trauma: correlation with angiographic and surgical findings.

PURPOSE: To determine the contrast material-enhanced computed tomographic (CT) criteria for selection of hemodynamically stable patients with blunt hepatic injury for angiographic evaluation. MATERIALS AND METHODS: Seventy-two patients with blunt liver injury underwent CT and hepatic angiography. Hepatic injuries were graded with CT-based classification. Scans were assessed for evidence of contrast extravasation and laceration or contusion extending into the hepatic vein(s), inferior vena cava, porta hepatis, or gallbladder fossa. Medical, angiographic, and surgical records were reviewed to determine angiographic findings, surgical indications and findings, and outcomes. RESULTS: Compared with hepatic angiography, CT was 65% (11 of 17 patients) sensitive and 85% (41 of 48 patients) specific for detection of arterial vascular injury. When CT severity grades 2 and 3 were analyzed, the sensitivity and specificity of CT were 100% (three of three patients) and 94% (34 of 36 patients), respectively (P <.001). Injury involving at least one major hepatic vein was found in 15 (88%) of 17 patients who required liver-related surgery and in 23 (42%) of 55 of the other patients (P <.01). CONCLUSION: CT-based criteria, including hepatic injury grade, signs of arterial vascular injury, and presence or absence of major hepatic venous involvement assists in selecting patients for hepatic angiography and those at increased risk of ongoing or delayed hepatic bleeding or other posttraumatic complications.

Imaging of diaphragmatic injuries.

Multiple imaging modalities are available for the preoperative diagnosis of diaphragmatic injury. Chest radiographs are the initial and most commonly performed imaging study to evaluate the diaphragm after trauma. When chest radiography is indeterminate, spiral computed tomography (CT) with thin sections and reformatted images is the next study of choice, particularly because most hemodynamically stable patients with blunt diaphragm injury will require an admission CT examination to evaluate the extent and anatomical sites of coexisting thoracoabdominal injuries. Magnetic resonance imaging is used to evaluate the diaphragm for patients with clinical suspicion but an indeterminate diagnosis after chest radiography and spiral CT.

Using CT to diagnose traumatic lumbar hernia.

OBJECTIVE: The objective of this study was to determine the CT findings of traumatic lumbar hernia in 15 patients and to discuss the mechanism and treatment of injury. CONCLUSION: CT can reveal traumatic lumbar hernia and show both the anatomy of disrupted muscular layers and the presence of herniated intraabdominal viscera or retroperitoneal fat.

Development of a DeltaglnA balanced lethal plasmid system for expression of heterologous antigens by attenuated vaccine vector strains of Vibrio cholerae.

We have previously shown that more prominent immune responses are induced to antigens expressed from multicopy plasmids in live attenuated vaccine vector strains of Vibrio cholerae than to antigens expressed from single-copy genes on the V. cholerae chromosome. Here, we report the construction of a DeltaglnA derivative of V. cholerae vaccine strain Peru2. This mutant strain, Peru2DeltaglnA, is unable to grow on medium that does not contain glutamine; this growth deficiency is complemented by pKEK71-NotI, a plasmid containing a complete copy of the Salmonella typhimurium glnA gene, or by pTIC5, a derivative of pKEK71-NotI containing a 1. 8-kbp fragment that directs expression of CtxB with a 12-amino-acid epitope of the serine-rich Entamoeba histolytica protein fused to the amino terminus. Strain Peru2DeltaglnA(pTIC5) produced 10-fold more SREHP-12-CtxB in supernatants than did ETR3, a Peru2-derivative strain containing the same fragment inserted on the chromosome. To assess immune responses to antigens expressed by this balanced lethal system in vivo, we inoculated germfree mice on days 0, 14, 28, and 42 with Peru2DeltaglnA, Peru2DeltaglnA(pKEK71-NotI), Peru2(pTIC5), Peru2DeltaglnA(pTIC5), or ETR3. All V. cholerae strains were recoverable from stool for 8 to 12 days after primary inoculation, including Peru2DeltaglnA; strains containing plasmids continued to harbor pKEK71-NotI or pTIC5 for 8 to 10 days after primary inoculation. Animals were sacrificed on day 56, and serum, stool and biliary samples were analyzed for immune responses. Vibriocidal antibody responses, reflective of in vivo colonization, were equivalent in all groups of animals. However, specific anti-CtxB immune responses in serum (P

Helical CT of diaphragmatic rupture caused by blunt trauma.

OBJECTIVE: The purpose of this study was to determine the diagnostic sensitivity and specificity of helical CT with sagittal and coronal reformatted images in detecting diaphragmatic rupture after blunt trauma. MATERIALS AND METHODS: Chest and abdominal helical CT scans obtained in 41 patients with suspected diaphragmatic injury after major blunt trauma were reviewed by three observers who were unaware of surgical findings. Coronal and sagittal reformatted images were reviewed for each patient as well. Findings consistent with diaphragmatic injury, such as waistlike constriction of abdominal viscera (i.e., the "collar sign"), intrathoracic herniation of abdominal contents, and diaphragmatic discontinuity were recorded. Sensitivity and specificity of helical CT were calculated on the basis of surgical findings and clinical follow-up. RESULTS: Helical CT was performed preoperatively in 23 patients with diaphragmatic rupture (left, n = 17; right, n = 5; bilateral, n = 1). An additional 18 patients underwent helical CT to further evaluate suspicious findings seen on chest radiography at admission and were found to have an intact diaphragm. Sensitivity for detecting left-sided diaphragmatic rupture was 78% and specificity was 100%. Sensitivity for the detection of right-sided diaphragmatic rupture was 50% and specificity was 100%. The most common CT finding of diaphragmatic rupture was the collar sign, identified in 15 patients (sensitivity, 63%; specificity, 100%). Diaphragmatic discontinuity was seen in four patients. CONCLUSION: Helical CT, especially with the aid of reformatted images, is useful in the diagnosis of acute diaphragmatic rupture after blunt trauma. Helical CT can be used to detect 78% of left-sided and 50% of right-sided injuries.

Safety and immunogenicity of phoP/phoQ-deleted Salmonella typhi expressing Helicobacter pylori urease in adult volunteers.

Salmonella typhi Ty800, deleted for the Salmonella phoP/phoQ virulence regulon has been shown to be a safe and immunogenic single dose oral typhoid fever vaccine in volunteers. This promising vaccine strain was modified to constitutively express a heterologous protein of Gram negative bacterial origin, Helicobacter pylori urease subunits A and B, yielding S. typhi strain Ty1033. Seven volunteers received single oral doses of > or = 10(10) colony forming units of Ty1033; an eighth volunteer received two doses 3 months apart. Side effects were similar to those observed previously in volunteers who received the unmodified vector Ty800. All volunteers had strong mucosal immune responses to vaccination as measured by increases in IgA-secreting cells in peripheral blood directed against S. typhi antigens. Seven of eight volunteers had convincing seroconversion as measured by increases in serum IgG directed against S. typhi flagella and lipopolysaccharide antigens by ELISA. No volunteer had detectable mucosal or humoral immune responses to the urease antigen after immunization with single doses of Ty1033. A subset of three volunteers received an oral booster vaccination consisting of recombinant purified H. pylori urease A/B and E. coli heat labile toxin adjuvant 15 days after immunization with Ty1033. None of three had detectable humoral or mucosal immune responses to urease. Expression of a stable immunogenic protein in an appropriately attenuated S. typhi vector did not engender detectable mucosal or systemic antibody responses; additional work will be needed to define variables important for immunogenicity of heterologous antigens carried by live S. typhi vectors in humans.

CT detection of serious internal and skeletal injuries in patients with pelvic fractures.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the percentage of patients with known pelvic fractures who have additional findings of intraabdominal injury, as diagnosed at abdominal computed tomography (CT), and to determine if patients with specific types or patterns of fractures are more likely to have additional injuries. MATERIALS AND METHODS: The authors reviewed the medical records of 200 consecutive patients (125 women, 75 men; age range, 4-86 years) who had been admitted to a level 1 trauma center with osseous pelvic injury secondary to blunt trauma and who had undergone abdominal CT examinations. Abdominal CT findings in these patients were classified as negative, positive, or minimal and correlated with mechanism of pelvic fracture. RESULTS: Sixty-five (32%) of the 200 patients had negative CT findings, 43 (22%) had findings attributable to the trauma but required no follow-up, and 92 (46%) had positive findings that required nonsurgical management or exploratory laparotomy. Additional pelvic fractures were identified in 63 (32%) patients. The highest prevalence of additional injuries was in patients with Malgaigne fractures (four of 15, 27%) or bilateral pubic rami fractures (six of 18, 33%). CONCLUSION: CT examinations revealed that 135 (68%) of 200 patients with pelvic fractures secondary to blunt trauma had concomitant internal or skeletal injuries and that 92 (46%) patients had injuries severe enough to require nonsurgical management or exploratory laparotomy. Patients with bilateral pubic rami fractures or Malgaigne fractures were particularly prone to additional injuries; therefore, abdominal CT examinations are recommended in these patients.

phoP/phoQ-deleted Salmonella typhi (Ty800) is a safe and immunogenic single-dose typhoid fever vaccine in volunteers.

The phoP/phoQ virulence regulatory genes of Salmonella typhi Ty2 were deleted, and the resultant strain (Ty800) was tested as a live attenuated typhoid fever vaccine in human volunteers. Groups of 2 or 3 subjects received single oral doses of 10(7), 10(8), 10(9), or 10(10) cfu. Two volunteers who received the largest dose had self-limited side effects; no bacteremias were detected. Ten of 11 subjects had evidence of intestinal immune responses to the vaccine as measured by increases in S. typhi lipopolysaccharide-specific IgA-secreting cells in peripheral blood samples. Humoral immune responses were measured and compared with those of control vaccinees who received 4 oral doses of S. typhi Ty21a. In the most sensitive assays, 9 of 11 volunteers and 5 of 8 Ty21a control vaccinees had evidence of IgG directed against S. typhi antigens. Ty800 is safe, and single oral doses are highly immunogenic in humans.

Peru-15, an improved live attenuated oral vaccine candidate for Vibrio cholerae O1.

Cholera vaccine candidate Peru-15 was derived from a Vibrio cholerae O1 El Tor Inaba strain by deleting the cholera toxin genetic element, introducing the gene encoding cholera toxin B subunit into recA, and screening for nonmotility. In a controlled study, Peru-15 (2 x 10(8) cfu) was administered to 11 volunteers. No vaccinee developed diarrhea, and 10 of 11 had > 4-fold rises in vibriocidal antibody titers. One month later, 5 vaccinees and 5 control volunteers were challenged with wild type V. cholerae O1. Four of 5 controls developed diarrhea (mean, 1.9 L). Two Peru-15 vaccinees developed diarrhea, 1 with < 0.3 L and 1 with approximately 1.0 L; this latter volunteer had not developed a significant vibriocidal immune response to vaccination. Peru-15 shows promise as a single-dose, oral cholera vaccine that is safe, immunogenic, and protective.

Heterologous antigen expression in Vibrio cholerae vector strains.

Live attenuated vector strains of Vibrio cholerae were derived from Peru-2, a Peruvian El Tor Inaba strain deleted for the cholera toxin genetic element and attRS1 sequences, which was developed as a live, oral vaccine strain. A promoterless gene encoding the Shiga-like toxin I B subunit (slt-IB) was inserted in the V. cholerae virulence gene irgA by in vivo marker exchange, such that slt-IB was under transcriptional control of the iron-regulated irgA promoter. slt-IB was also placed under transcriptional control of the V. cholerae heat shock promoter, htpGp, and introduced into either the irgA or lacZ locus, or both loci, on the chromosome of Peru-2, generating JRB10, JRB11, or JRB12, respectively. A new technique was used to perform allelic exchange with lacZ. This method uses plasmid p6891MCS, a pBR327 derivative containing cloned V. cholerae lacZ, to insert markers of interest into the V. cholerae chromosome. Recombinants can be detected by simple color screening and antibiotic selection. In vitro measurements of Slt-IB produced by the vector strains suggested that expression of Slt-IB from the irgA and htpG promoters was synergistic and that two copies of the gene for Slt-IB increased expression over a single copy. The V. cholerae vectors colonized the gastrointestinal mucosa of rabbits after oral immunization, as demonstrated by very high serum antibody responses to V. cholerae antigens. Comparison of the serologic responses to the B subunit of cholera toxin (CtxB) following orogastric inoculation either with the wild-type C6709 or with Peru-10, a strain containing ctxB regulated by htpGp, suggested that both the cholera toxin and heat shock promoters were active in vivo, provoking comparable immunologic responses. Orogastric inoculation of rabbits with vector strains evoked serum immunoglobulin G (IgG) responses to Slt-IB in two of the four strains tested; all four strains produced biliary IgA responses. No correlation was observed between the type of promoter expressing slt-IB and the level of serum IgG or biliary IgA response, but the vector strain containing two copies of the gene for slt-IB evoked greater serum IgG responses than strains containing a single copy, consistent with the increased expression of Slt-IB from this strain observed in vitro. A comparison of the serum and biliary antibody responses to Slt-IB expressed from htpGp versus CtxB expressed from the same promoter suggested that CtxB is a more effective orally delivered immunogen.

Safety, immunogenicity, and efficacy of live attenuated Vibrio cholerae O139 vaccine prototype.

New vaccines are needed to prevent cholera caused by Vibrio cholerae O139. Attenuated V cholerae O139 vaccines were made by deleting multiple copies of the cholera-toxin genetic element from two virulent strains of the organism, MO10 and AI4456. The deletion mutants were further modified by insertion of a construct that encoded the B subunit of cholera toxin, thus generating strains Bengal-3 and VRI-16. A stable spontaneous non-motile derivative of Bengal-3 was isolated and designated Bengal-15; VRI-16 is naturally non-motile. Bengal-3, Bengal-15, and VRI-16 were evaluated as oral single-dose cholera vaccine candidates in 4 volunteers each, and MO10 was given to 3 volunteers. 1 of 4 volunteers who received Bengal-3 and all 3 who received MO10 had diarrhoea. VRI-16 caused no significant symptoms but was not immunogenic. Bengal-15 produced few symptoms and was nearly as immunogenic as MO10. Subsequently, Bengal-15 was given to 10 volunteers at a dose of 10(8) colony-forming units. No volunteers had diarrhoea, and other subjective symptoms were as common in vaccinees as in 3 buffer recipients. 1 month after vaccination, 7 vaccinees, the 3 buffer recipients, and 3 unimmunised subjects were challenged with 5 x 10(6) colony-forming units of V cholerae O139. 5 of 6 controls had cholera-like diarrhoea. By contrast, 1 of 7 vaccinees had diarrhoea, which was mild and had a long incubation period. Vaccine protective efficacy was 83%. Our results indicate the Bengal-15 is a safe live attenuated vaccine candidate for cholera caused by the O139 serogroup.

Development of a live, oral, attenuated vaccine against El Tor cholera.

Vibrio cholerae El Tor strains from Peru, Bangladesh, and Bahrain were attenuated by deletion of a genetic element that encodes virulence factors and RS1. The B subunit of ctx (ctxB) was reintroduced into the recA gene of the deletion mutants, rendering them unable to recombine with exogenous genetic elements and generating Peru-3, Bang-3, and Bah-3. Fifteen volunteers received one dose of various vaccine strains at 4 x 10(6) to 1 x 10(8) cfu. All strains colonized the gut. A > or = 4-fold rise in vibriocidal titer was observed in 14 volunteers, with titers of > or = 1600 in 13. Peru-3 was the least reactogenic, but 2 of 6 volunteers had loose stools. Peru-14, a filamentous motility-deficient mutant of Peru-3, was well tolerated and colonized 18 of 21 volunteers at doses of 2 x 10(6) to 1 x 10(9) cfu. Also, when 8 Peru-3 or Peru-5 vaccinees, 5 Peru-14 vaccinees, and 8 controls were challenged with 2 x 10(6) cfu V. cholerae El Tor Inaba (N16961), 11 vaccinees were protected compared with no controls. Peru-14 shows promise as a safe, effective, single-dose oral vaccine against El Tor cholera.