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Biomedical subjects

C J Hauser

Publications and source records attributed to C J Hauser.

At least 37 records · Page 2Linked to original sources

Suppression of natural killer cell activity in patients with fracture/soft tissue injury.

BACKGROUND: Natural killer cells (NKCs) participate in "innate" cell-mediated immunity. Fracture/soft tissue injuries are cytokine rich and may influence cell-mediated immunity. OBJECTIVE: To study the effects of fracture cytokines on NKC function. DESIGN: A case-control study. SETTING: A level I trauma center and laboratory in a university medical center. PARTICIPANTS: Patients requiring open fracture fixation and healthy volunteers. INTERVENTIONS: Fracture supernatants and peripheral plasma were collected during open fracture fixation. Volunteer mononuclear cells were used as effector (NKC) sources. Mononuclear cells were preincubated with fracture supernatants, paired peripheral plasma, or normal plasma under various conditions. MAIN OUTCOME MEASURES: Natural killer cell lysis of K562 target cells was assessed by chromium 51 release. RESULTS: Fracture supernatants suppressed NKC function more rapidly than peripheral plasma. Fracture supernatants from 1 to 4 days after injury were most suppressive. Inactivation of complement and reactive oxygen species failed to restore lysis. Neutralizing antibodies to interleukin 4 and interleukin 10 further suppressed lysis. Antibodies to transforming growth factor beta1 failed to restore lysis. The addition of interferon gamma did not restore lysis but the addition of interleukin 12 did. CONCLUSIONS: Fracture supernatants and peripheral plasma from patients with fractures suppress NKCs. The responsible mediators may be concentrated in fracture/soft tissue injuries. Responses to manipulation of the cytokine environment suggest that fracture cytokines may impair cooperation between NKCs and accessory cells.

Adult↗

Psychopathologic risk factors for intentional and nonintentional injury.

OBJECTIVE: Trauma has a high rate of recurrence, suggesting that some people are more injury-prone than others. This study was performed to evaluate some of the psychological and social factors that might influence the likelihood of traumatic injury. METHODS: A case-control study was conducted to evaluate the relationship between selected psychosocial factors and traumatic injury. At a Level I trauma center, victims of intentional trauma (excluding attempted suicide), victims of nonintentional trauma, and patients undergoing elective surgery were interviewed by a person blinded to the purposes of the study. They were given an intelligence test and underwent a structured interview, yielding psychiatric diagnostic categories established in the third edition of the Diagnostic and Statistical Manual of Mental Disorders, Revised (DSM-III-R). RESULTS: Trauma patients were younger than elective surgery patients (p < 0.01) and were more likely to be men (p < 0.01). Victims of intentional injury had a higher probability of alcohol use (p < 0.01) and admitted illicit drug use (p < 0.001) than either nonintentional injury victims or elective surgery patients. Victims of intentional injury were more likely to be unemployed than those in the other two groups (p < 0.02), whereas elective surgery patients were more likely to be retired (p < 0.05) or to be disabled (p < 0.0001). The average intelligence score was slightly above the median in the nonintentional trauma group and in the control group (55th percentile and 54th percentile, respectively), compared with a mean intelligence score equivalent to the 35th percentile in the victims of intentional trauma (p < 0.001). Thirty percent of elective surgery patients met diagnostic criteria for at least one category of psychopathology, compared with 50% of nonintentional trauma patients, and 63% of intentional trauma patients (p < 0.01, trauma vs. elective surgery). Logistic regression analysis identified six variables that were independently associated with an increased tendency to be a victim of trauma: younger age, lower intelligence, antisocial personality, mental retardation, depression, and low income. CONCLUSIONS: Victims of trauma, both nonintentional, and especially intentional, have a high incidence of psychopathology. Victims of intentional trauma have significantly lower intelligence scores than either nonintentional injury or elective surgery patients. The high incidence of unemployment, alcohol abuse, and illicit drug use in victims of intentional injury might provide several opportunities for trauma prevention programs. Underlying psychological disorders will have to be addressed to reduce the likelihood of becoming a victim of trauma.

Accident Proneness↗

The immune microenvironment of human fracture/soft-tissue hematomas and its relationship to systemic immunity.

The immune environment of human soft-tissue injury is unstudied. We studied fracture soft-tissue hematomas (FxSTH) in 56 patients with high-energy bony fractures. FxSTH serum and mononuclear cells (MNC) as well as fracture patient plasma and blood MNC were studied. Twenty healthy controls donated plasma and MNC. Soluble tumor necrosis factor (TNF)-alpha, interleukin (IL-1 beta, IL-2, 6, 8, 10, 12, and interferon-gamma were studied by enzyme linked immunosorbent assay. Cells were studied by flow cytometry after cell-membrane stains for CD-14, TNF-alpha (mTNF), and human leukocyte antigen-DR, or intracellular stains for TNF (icTNF) and IL-10. Thirty-six patients with Injury Severity Score < 15 were analyzed further to evaluate the effects of isolated fracture on systemic immunity. Cytokines were rarely detectable in control plasma. TNF-alpha, IL-1 beta, IL-2, and interferon-gamma were rarely found in FxSTH serum or fracture patient plasma. All FxSTH sera were rich in IL-6, peaking before 48 hours (12,538 +/- 4,153 vs. 3,494 +/- 909 pg/mL, p = 0.02, U test). In Injury Severity Score < 15, IL-6 was not detectable in most early fracture patient plasma, but rose after 48 hours (p = 0.028). FxSTH serum IL-8 peaked after 48 hours (440 +/- 289 vs. 4,542 +/- 1,219 pg/mL, p = 0.006) and circulating IL-8 appeared after 72 hours. IL-6 and IL-8 showed gradients from FxSTH serum to paired PtS (p < 0.05, Wilcoxon). IL-10 was abundant (884 +/- 229 pg/mL) in FxSTH serum < 24 hours old. FxSTH serum IL-12 peaked late (3,323 +/- 799 pg/mL, day 4-7) then fell (p < 0.001, analysis of variance). Only IL-12 was higher in fracture patient plasma (1,279 +/- 602 pg/mL) than FxSTH serum (591 +/- 327 pg/mL) during the first 48 hours (p = 0.032, U test). On flow cytometry, control monocytes expressed 201 +/- 31 mTNF sites/cell, but icTNF was absent. mTNF was up-regulated after injury more in FxSTH monocytes (3,202 +/- 870 sites/cell) than peripheral blood monocytes (584 +/- 186 sites/cell) (p < 0.05 vs. peripheral blood monocytes by Wilcoxon, p < 0.001 vs. control monocytes by U test). Intracellular IL-10 was abundant in all MNC, but varied widely after injury. Fracture and peripheral blood monocytes expressed far less human leukocyte antigen-DR than control monocytes. Fractures create an inflammatory local environment. Proximal mediators are cell-associated and relatively confined to the wound, but soluble IL-6, IL-8, and IL-10 are abundant and probably exported. Systemic MNC have complex responses to local injuries. These may reflect the combined impact of multiple soluble cytokines initially generated within the wound. FxSTH appear to be a potentially important source of immunomodulatory cytokines in trauma.

Adolescent↗

Laparoscopy in trauma.

Laparoscopy is a nearly century-old technique that has experienced a resurgence of interest from surgeons since the development of technology that has broadened its applications. Although laparoscopy has been used to evaluate patients with possible abdominal trauma, its use for this purpose is limited by the availability of other diagnostic procedures that may be more suitable for particular circumstances and are more accurate for certain injuries. Laparoscopy is contraindicated in patients who are hypovolemic or hemodynamically unstable and should not be performed in patients with clear indications for celiotomy. It may not be appropriate for patients with cardiac dysfunction, nor for those with significant head injuries who are at risk for intracranial hypertension. Its best applications may be in stable patients with stab wounds or those with tangential gunshot wounds of the abdomen. The likelihood of missing hollow visceral injuries depends upon the indications for conversion to celiotomy. If peritoneal violation or the presence of a small amount of blood in the peritoneal cavity is used as an indication for celiotomy, then the missed injury rate will be low but the unnecessary celiotomy rate will be diminished only slightly compared with a policy of mandatory celiotomy. Excessive enthusiasm for laparoscopy in trauma might result in its use when other diagnostic measures or simple observation are more appropriate. The desire to perform a procedure can be compelling, especially in circumstances in which the general surgeon would not operate upon a patient but simply provide postoperative care after other surgeons have operated. The use of laparoscopy for these purposes can only be condemned, as it increases the costs and risks of care without improving the outcome. The role of laparoscopy in trauma is evolving, and further research into its diagnostic role and therapeutic applications is clearly needed.

Abdomen↗

Abbreviated Injury Scale does not reflect the added morbidity of multiple lower extremity fractures.

OBJECTIVES: To determine if patients with multiple lower extremity fractures have worse outcomes than do patients with isolated femur fractures, and to determine if the Abbreviated Injury Scale (AIS) should distinguish between single and multiple lower extremity fractures. DESIGN: A retrospective study. MATERIALS AND METHODS: All blunt trauma patients at least 15 years of age treated at a level 1 trauma center from January 1990 through December 1993. Three groups of patients were selected. Group 1 included 50 patients whose only significant injury was a diaphyseal femur fracture. They had no other long bone fractures, minimal injuries to other body areas, and an Injury Severity Score (ISS) < or = 14. Group 2 was consisted of 29 patients with a femur fracture, at least one other diaphyseal lower extremity fracture, and also an ISS < or = 14. Group 3 consisted of 23 patients who had fracture patterns similar to those of group 2, but also had more severe nonextremity injuries (ISS > or = 15). Hospital morbidity and mortality rates were compared with t tests or chi-square analysis. Type 1 error probability was established at p < 0.05. MEASUREMENTS AND MAIN RESULTS: Compared with patients in group 1, patients in group 2 had an identical ISS (10.1 vs. 10.6, respectively), but had higher transfusion requirements (0.3 vs. 3.9 units), more days in the intensive care unit (ICU) (0.02 vs. 1.4), a higher incidence of adult respiratory distress syndrome (ARDS) (0 vs. 14%), longer hospital stays (6.0 vs. 14.8 days), greater disability at discharge (disability score 2.2 vs. 3.2), and a higher mortality rate (0 vs. 3.4%; p < 0.05 all variables). Patients in group 3 had worse outcomes than the other two groups: ISS = 30.1; transfusions = 11.9 units; ICU days = 9.1; ARDS incidence = 26%; hospital days = 29.9; disability score = 3.9; mortality = 26% (p < 0.05). CONCLUSIONS: Although AIS and ISS appropriately reflect the impact of extraskeletal injuries in patients with femur fractures, they do not adequately reflect the increased morbidity associated with multiple lower extremity fractures. The AIS-Extremity Score may need to be upgraded for multiple long bone fractures of the lower extremities.

Abbreviated Injury Scale↗

Production of interleukin-10 in human fracture soft-tissue hematomas.

Clinical trauma suppresses immunity and experimental wound fluids have been shown to be immunosuppressive. To ascertain whether human wounds contain immunosuppressive cytokines, we assayed serum from fracture/soft-tissue hematomas (FSTH) of 22 patients for interleukin (IL)-10, transforming growth factor (TGF)-beta 1, and IL-4. Results were correlated to concurrent plasma cytokine concentrations in the same patients and in volunteer plasma. IL-10 was present in high concentration (1376 +/- 539 pg/mL) in all (7/7) FSTH < 24 h old. In FSTH > 24 h old, IL-10 was found intermittently and at lower levels (239 +/- 106 pg/mL, p = .011 vs. FSTH < 24 h old). IL-10 was rarely detectable in fracture patient plasma and never detectable (< 20 pg/mL) in normal plasma. No significant variations of IL-4 or total TGF-beta 1 were found in FSTH or plasma. FSTH are significant potential sources of IL-10 activity in trauma patients, which may be overlooked when only plasma is assayed. The potential for a relationship between cytokines found locally at sites of injury and clinical immune modulation in trauma requires further study.

Adult↗

Regional macrophage activation after injury and the compartmentalization of inflammation in trauma.

The mononuclear phagocyte or macrophage (M phi) system is an important early participant in the human immune response to injury. M phi are uniquely able to transduce a broad variety of nonspecific physical and chemical stimuli generated in traumatized tissues as well as specific immune signals (such as cytokines) into coherent response patterns. Thus, M phi occupy a central position in the overall response in that they can initiate specific, cognate immune responses to injury. M phi are both responsive to cytokine signals and key inducers of cytokine-mediated patterns of response in other cells. Not only do the responses of M phi in different diseases states very widely, but these responses may vary from location to location and over time in the same organism. This article examines the role of M phi in the response to injury, focusing on local activities and the hypothesis that local M phi response patterns (and their pathologic loss) may be involved in the generation of immune-mediated organ injury distant from sites of direct trauma.

Animals↗

Tumor necrosis factor alpha gene expression in human peritoneal macrophages is suppressed by extra-abdominal trauma.

BACKGROUND: Trauma is believed to activate immunocytes but paradoxically also increases the risk of intraperitoneal infection. OBJECTIVE: To investigate these events by evaluating changes in the cytokine control networks of human peritoneal macrophages (PM phi) early after trauma. DESIGN: Case-control study comparing cytokine messenger RNA (mRNA) expression by PM phi from patients with extra-abdominal trauma with that of both peripheral blood mononuclear cells (PBM) and PM phi obtained from healthy individuals. SETTING: Level I trauma center and basic science laboratory in a university hospital center. PATIENTS: Six patients with polytrauma (Injury Severity Score, > or = 15) with clinically negative diagnostic peritoneal lavages performed on routine indications at admission to the emergency department and six healthy age- and sex-matched individuals undergoing inguinal herniorrhaphy under local anesthesia. INTERVENTIONS: Peritoneal macrophages were isolated from diagnostic peritoneal lavages in trauma patients. Identical lavages were performed through the hernia sac in the control group. MEASUREMENTS: Cellular RNA was assayed for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta, IL-6, and IL-10 message by semiquantitative reverse-transcription polymerase chain reaction. RESULTS: Normal PM phi expressed high levels of TNF-alpha mRNA relative to PBM, but expression of the other proinflammatory cytokines was equivalent to that of PBM. Peritoneal macrophage expression of TNF-alpha mRNA was markedly (64-fold) decreased after trauma (P < .001), when PBM expression of IL-10 mRNA was increased (P = .03). CONCLUSIONS: Human PM phi constitutively show high levels of TNF-alpha message expression, and this is down-regulated by polytrauma. This might constitute a functionally "primed" state. If so, TNF-alpha down-regulation might contribute to functional PM phi suppression after systemic injury.

Adult↗

Human peripheral mononuclear cells do not show proinflammatory patterns of cytokine transcription in early trauma: a preliminary report.

Injury has been hypothesized to cause inflammation through systemic release of lipopolysaccharide and pro-inflammatory cytokines, but this has proved difficult to demonstrate in humans. We looked for evidence of an inflammatory pattern of cytokine gene expression by peripheral blood mononuclear cells (PBM) in six polytraumatized patients (ISS = 25 +/- 8) upon ER admission, and in six matched healthy controls. PBM tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-4, IL-6, IL-10, and interferon (IFN)-gamma message was assessed by semi-quantitative reverse-transcription polymerase chain reaction. No increase in expression of any of the pro-inflammatory cytokines (tumor necrosis factor-alpha, IL-1 beta, or IL-6) was found after trauma, and IFN-gamma tended to decrease. Of the immunosuppressive cytokines, IL-10 expression increased 5-fold (p < .05) but no change in IL-4 was discerned. This pattern is fundamentally different from the cytokine expression patterns expected with sepsis or exposure to lipopolysaccharide. These findings are inconsistent with the occurrence of systemic endotoxemia and subsequent global immunocyte activation early after trauma.

Adolescent↗

Pancreatic injuries from blunt trauma.

Pancreatic injuries from blunt trauma are infrequent, and their diagnosis and management can be extremely difficult. Over the past 10 years we treated 13 patients with major pancreatic injuries from blunt trauma. Twelve had been involved in motor vehicle collisions, none of whom were wearing seat belts. One patient was injured in an assault. Only five patients had physical findings suggesting intra-abdominal injury. Serum amylase levels were elevated in seven of the nine patients (78%) in whom this test was obtained. Computed tomography scans demonstrated pancreatic injury in three of the four patients in whom it was performed. The five patients in whom peritoneal lavage was performed had free intraperitoneal blood from injuries to other abdominal viscera. One injury was diagnosed by ultrasound. Injuries were equally distributed throughout the pancreas, with two injuries in the head, three in the body, five in the tail, and three with injuries in both the head and the body. Five patients had ductal injuries. All patients underwent celiotomy. Eight patients required no operative management of their pancreatic injuries other than drainage. Injury Severity Score averaged 28.5 +/- 2.6 (mean +/- standard error), and mean hospital stay was 31 +/- 9.8 days. One patient with delayed diagnosis of a pancreatic injury developed a pseudocyst, but all other complications and prolonged hospitalizations were due to injuries to the head, chest, other abdominal organs, or extremities. All patients survived. The diagnosis of blunt pancreatic injury requires a high index of suspicion, and diagnostic studies may demonstrate only subtle signs of injury. Most injuries can be managed by localized resection and/or drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Injuries↗

Postsurgical gout.

Although catabolic events are known to precipitate gout, postsurgical gout has rarely been reported. We identified the charts of 302 patients treated over a 10-year period in a university center who carried the diagnosis of gout and who also had a surgical procedure. Fifty-two patients (42 male, 10 female) were found to have had a postsurgical episode of gouty arthritis. Ages ranged from 20 to 82 years (mean 60.1 +/- 2.1). Forty-five patients had a history of gout, 22 of whom were receiving medication and 23 who were not receiving chronic therapy. In seven patients the postsurgical event was their first attack. Attacks occurred 1-17 days (mean 4.2 +/- 0.5 [SE]) after surgical admission. Most attacks were in the lower extremity, but classic podagra was uncommon. Essentially all patients were febrile (100.7 +/- 0.2 degrees F) compared with admission (99.0 +/- 0.1 degree) (P < 0.001). There was a trend toward leukocytosis in the group as a whole, but the relationship of leukocytosis to the gout attack was most clearly seen in patients admitted for noninflammatory conditions (9.4 +/- 0.7 versus 12.8 +/- 0.8 x 1000 WBC/mm3, P < 0.001). Uric acid levels were elevated but did not follow the course of the attack. Most patients underwent a variety of tests and consultative evaluations because of their undiagnosed febrile episode. Once the diagnosis was established, all patients responded quickly to nonsteroidal anti-inflammatory drugs or colchicine. Despite evidence of a significant inflammatory response, no patient proved to have a suppurative focus as the source of their febrile episode.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Major gastroenteric injuries from blunt trauma.

Hollow visceral injuries are far less common in blunt abdominal trauma than in penetrating abdominal trauma. From 1982 through 1993 we treated 50 patients with 57 major blunt injuries to the gut, defined as perforation, transection, or devascularization. Thirty-two patients (64%) were injured in motor vehicle collisions. Of these, 29 wore no restraints; three were wearing lap belts (none wore lap-shoulder restraints). Mean injury Severity Score (ISS) in patients wearing lap belts was 13.3, compared with 28.6 in the 29 patients who were not using restraint devices (P < 0.01). Small bowel perforations were the most frequent injuries, followed by devascularization of the small bowel, colorectal injuries, duodenal, and gastric perforations. ISS and mortality rates were lowest in small bowel injuries and higher in the less common colonic and gastroduodenal injuries. Except for those patients with perforations of the small bowel, most patients had associated injuries to the head, chest, or abdominal solid organs that were largely responsible for morbidity and mortality. Injuries to the abdominal hollow viscera are unusual following blunt trauma, but are the result of very high energy truncal trauma, and are associated with multiple additional injuries. Most alert patients had physical findings suggestive of peritoneal irritation, but when diagnostic testing was necessary, peritoneal lavage was superior to computed tomography scanning (false negatives = 6.7% versus 36%, respectively; P < 0.05). A high index of suspicion is necessary to avoid diagnostic delays that can lead to severe complications and death.

Accidents, Traffic↗

Laparoscopic fenestration of a giant simple hepatic cyst. Case report and technical considerations.

The management of symptomatic large, simple hepatic cysts has evolved toward the use of wide unroofing or "fenestration" in instances where patients are not rendered asymptomatic by percutaneous aspiration. We report adoption of the technique of fenestration of such hepatic cysts to the laparoscopic route. Laparoscopic fenestration appears able to accomplish all of the aims of transabdominal fenestration in appropriately selected patients.

Cysts↗

Hemostasis of solid viscus trauma by intraparenchymal injection of fibrin glue.

Fibrin glue (FG) is an effective hemostatic agent applied topically to the spleen. In this study, FG was found to be an effective hemostatic agent when applied topically in standardized wounds of the canine liver, spleen, and pancreas. It was markedly more effective, however, when injected intraparenchymally. In a case of severe blunt trauma in a patient with acute alcoholic hepatitis, intraparenchymal FG was lifesaving. Fibrin glue is a useful adjunct in the management of trauma to all the abdominal solid viscera. Intraparenchymal injection is the preferred mode of FG application.

Administration, Topical↗

Surgical management of fungal peripheral thrombophlebitis.

Fungal infection of central venous catheters is well described. Peripheral fungal thrombophlebitis, however, has only been recognized recently, is thought rare, and is poorly characterized as to clinical presentation and treatment. We report the cases of eight patients with peripheral Candida thrombophlebitis. Patients were elderly and critically ill. All had received broad-spectrum antibiotics. Skin colonization appeared the source of contamination. Sepsis, shock, and organ failure were frequent. Physical findings of fungal phlebitis may be subtle, and diagnosis is often delayed. Multiple sites are frequently involved. Treatment necessitates radical excision of suspected veins and systemic antifungal chemotherapy. Persistent fungemia suggests inadequate phlebectomy or the existence of further affected veins. Peripheral thrombophlebitis is probably a common source of fungal sepsis and should be considered in all patients with fungemia. Without aggressive surgical intervention, survival is unlikely.

Aged↗