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William G Cioffi

Publications and source records attributed to William G Cioffi.

29 records · Page 2Linked to original sources
PubMed2003

Portal venous gas detected by computed tomography: is surgery imperative?

BACKGROUND: Portal vein gas (PVG) has historically been associated with mortality rates of 75% or higher and mandatory abdominal exploration. The following study reassesses the clinical significance of gas in the portal venous system detected by computed tomography (CT) and reevaluates the need for surgical intervention in that setting. METHODS: We performed a retrospective chart review of 26 patients presenting with gas in the portal venous system as imaged by CT between August 1, 1993 and April 8, 2001. Characteristics assessed included age, sex, clinical presentation and course, additional CT findings, diagnosis, surgical versus non-surgical management, surgical findings, pathologic correlation, and mortality. RESULTS: Of the 26 patients who had gas in the portal venous system by CT, 11 underwent surgery to determine underlying pathology. Of those who underwent surgery, 8 survived to be discharged while 3 died (73% surgical survival). The survivors presented with gastrointestinal related signs/symptoms and were found at the time of surgery to have adhesions, non-surgically treated inflammation, unclear pathology, or resectable lesions. Those who died all demonstrated marked bowel ischemia intraoperatively. Among patients who did not undergo surgery, 9 survived and 6 died (60% nonsurgical survival). Those who survived presented either asymptomatically or with pathology including acute pancreatitis, recent hypotensive episode, uncomplicated diverticulitis, unresectable colon cancer, or infectious etiology. Those who died were poor surgical candidates or status postvascular procedure. The overall survival in patients with portal venous gas by CT was 65%. CONCLUSION: Portal venous gas on CT is associated with a wide range of pathologies that do not necessarily warrant surgical management. Clinical presentation should be correlated with the presence of PVG and other associated CT findings prior to deciding whether surgery should be performed.

Adult↗
PubMed2003

Inhibition of CD1d activation suppresses septic mortality: a role for NK-T cells in septic immune dysfunction.

BACKGROUND: Studies indicate that following septic insult there is development of generalized immune dysfunction in T cells, B cells and phagocytes, which is thought to contribute to morbidity and mortality. Specifically, there is a shift in the lymphocytes of septic animals toward an increased release of Th2 cytokines. NK-T cells have been shown to contribute to propagation of the Th2 response. The influence of NK-T cells on the immune response to septic challenge is poorly understood. In this study, we examine whether NK-T cells contribute to the immune dysfunction seen following the onset of polymicrobial sepsis, as produced by cecal ligation and puncture (CLP). MATERIALS AND METHODS: Male 129S1/SvImJ mice were pretreated with either rat IgG (isotypic control) or monoclonal antibody to CD1d (clone 1B1) (0.5 mg), which blocks signaling/antigen presentation via the CD1d cell surface receptor, thereby, ablating the activation and differentiation of the NK-T cells. Septic survival with and without anti-CD1d (CLP/CD1d) pretreatment was assessed. Mice sacrificed 24 h after CLP were assessed for change in splenic %NK-T cell (via flourescense activated cell sector) and for splenic, hepatic, and lymphoid/macrophage production of pro-inflammatory or anti-inflammatory cytokines (via enzyme-linked immunosorbent assay). RESULTS: Administration of anti-CD1d reduced septic mortality 35% at 6-10 d (n = 23 mice/group) (P <.05). There was a consistent increase in the %CD3(+) NK1.1(+) cell population (NK-T cells) in septic mice (1.706%), which was markedly suppressed by pretreatment with anti-CD1d (0.592%). IL-6 and IL-10 levels were suppressed by anti-CD1d in the spleen and blood. CONCLUSIONS: Together these findings imply not only that NK-T cells may play a role in mediating the immune suppression seen in bacterial sepsis, but that inhibition of their activation promotes survival to septic challenge.

Animals↗
PubMed2003

Implementation of a tertiary trauma survey decreases missed injuries.

BACKGROUND: Missed injuries (MIs) adversely affect patient outcome and damage physician/institutional credibility. The primary and secondary surveys are designed to identify all of a patient's injuries and prioritize their management; however, MIs are prevalent in severely injured and multisystem trauma patients, especially when the patient's condition precludes completion of the secondary survey. We hypothesized that implementation of a routine tertiary trauma survey (TS) would reduce the incidence of MIs in a Level I trauma center. METHODS: In mid 1999, a TS form was created and TS documentation was mandated on all trauma intensive care unit (TICU) patients within 24 hours of admission. Patient data, including TS documentation and injury patterns, were concurrently recorded in an institutional trauma registry. Data were compared for patients admitted in 1997 to 1998 (PRE period) and 2000 to 2001 (POST period) using chi or Student's test. RESULTS: MIs decreased from 2.4% to 1.5% overall, and from 5.7% to 3.4% in TICU patients, after TS implementation. Patients with MIs were slightly older (49 vs. 45 years; > 0.05) and had higher Injury Severity Scores (21 vs. 10; < 0.05) than patients without MIs. Sixty percent of MI patients had brain injuries, 56% were admitted to the TICU, and 26% went directly from the emergency department to the operating room. The large majority of MIs in the POST period were detected in patients not undergoing timely TS. CONCLUSION: ICU patients-particularly brain injury victims and those undergoing emergent surgical procedures-appear to be at highest risk for MI. Implementation of a standardized TS decreased MIs by 36% in our Level I trauma center, and more timely TS would likely have further reduced MIs. A TS should be routine in trauma centers.

Adult↗
PubMed2003

Differential effects of macrophage inflammatory chemokine-2 and keratinocyte-derived chemokine on hemorrhage-induced neutrophil priming for lung inflammation: assessment by adoptive cells transfer in mice.

Prior studies have shown that hemorrhage (Hem) can serve as a priming stimulus for acute lung injury (ALI) triggered by subsequent septic challenge (cecal ligation and puncture, CLP). Furthermore, we have reported that in vivo antibody neutralization of the chemokines, macrophage inflammatory chemokine-2 (MIP-2) and keratinocyte-derived chemokine (KC), immediately after Hem appears to differentially effect the onset of ALI. However, although we hypothesize that this is due to divergent effects of MIP-2 and KC on Hem-induced neutrophil (PMN) priming, this has not been tested. To examine this hypothesis, PMN donor mice were Sham-Hem or Hem for 90 min at 35 +/- 5 mmHg and were then administered anti-MIP- 2 (Hem/anti-MIP2), anti-KC (Hem/anti-KC), or nonspecific immunoglobulin (Ig) G (Hem/IgG) during resuscitation (Ringer's lactate = four times the amount of drawn blood volume). Twenty-four hours post-Hem, the peripheral blood PMN were purified from these donor animals and were introduced into PMN-depleted recipient mice [depleted by prior anti-Gr1 (mouse PMN-specific marker) antibody treatment]. One hour after PMN transfer, recipient mice were subjected to CLP, euthanized 24 h later, and plasma as well as lung tissue samples were collected. PMN influx was assessed by myeloperoxidase assay (MPO; microU/mg protein) and histologically (IL-6, MIP-2, KC, and IL-10 levels) by enzyme-linked immunoabsorbant assay (ELISA; ng/mg). The results show that donor PMN from Hem/IgG but not Sham-Hem mice produce increased PMN influx (increased MPO, increased % esterase+ cells in tissue) into the lung and local tissue inflammation (increased IL-6/MIP-2, decreased IL-10) in PMN-depleted CLP recipient mice, which was attenuated in mice receiving cells from Hem/anti-MIP-2 but not Hem/anti-KC treated donors. Interestingly, although Hem/anti-MIP-2 donor PMN produced comparable effects on blood IL-6/MIP-2 levels, they were ineffective in altering the change in plasma IL-10/KC levels induce by Hem. Taken together, these data demonstrate that Hem-induced priming of PMN not only mediates ALI in the mouse, but also that this process is differentially effected by MIP2 and KC, despite the fact that both signal through CXCR2.

Adoptive Transfer↗
PubMed2003

Isolated brain injury as a cause of hypotension in the blunt trauma patient.

BACKGROUND: Emerging evidence suggests that, contrary to standard teaching, isolated brain injury may be associated with hypotension. This study sought to determine the frequency of isolated brain injury-induced hypotension in blunt trauma victims. METHODS: Hypotensive adult trauma patients were categorized according to the cause of hypotension: hemorrhagic (hemoglobin < 11.0), neurogenic, isolated brain, or other. Their clinical data and outcomes were compared. RESULTS: The cause of hypotension was hemorrhagic in 113 (49%), isolated brain injury in 30 (13%), neurogenic in 14 (6%), and other causes in 24 (10%). Fifty (22%) were indeterminate. Hemorrhagic, isolated brain, and neurogenic groups were similar in age, Injury Severity Score, and systolic blood pressure. The Glasgow Coma Scale score of the isolated brain group was lower than in the hemorrhagic group (4.4 vs. 8.4, p < 0.05). Mortality was higher in the isolated brain group compared with the hemorrhagic group (80% vs. 50%, p < 0.05) and in the subgroup of hemorrhagic patients with versus without associated brain injury (57% vs. 39%, p < 0.05). CONCLUSION: Isolated brain injuries account for 13% of hypotensive events after blunt trauma and are associated with an increased mortality compared with hemorrhage-induced hypotension. In hypotensive brain-injured patients, hemorrhagic sources should be excluded rapidly, and the focus should be on resuscitation.

Adult↗
PubMed2002

Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency.

Acute lung injury (ALI) leading to respiratory distress is a common sequela of shock/trauma, however, modeling this process in mice with a single shock or septic event is inconsistent. One explanation is that hemorrhage is often just a "priming insult," thus, secondary stimuli may be required to "trigger" ALI. To test this we carried out studies in which we assessed the capacity of hemorrhage alone or hemorrhage followed by septic challenge (CLP) to induce ALI. Lung edema, bronchoalveolar lavage interleukin (IL)-6, alveolar congestion, as well as lung IL-6, macrophage inflammatory protein (MIP)-2, and myeloperoxidase (MPO) activity were all increased in mice subjected to CLP at 24 but not 72 hours following hemorrhage. This was associated with a marked increase in the susceptibility of these mice to septic mortality. Peripheral blood neutrophils derived from 24 hours post-hemorrhage, but not Sham animals, exhibited an ex vivo decrease in apoptotic frequency and an increase in respiratory burst capacity, consistent with in vivo "priming." Subsequently, we observed that adoptive transfer of neutrophils from hemorrhaged but not sham-hemorrhage animals to neutropenic recipients reproduce ALI when subsequently septically challenged, implying that this priming was mediated by neutrophils. We also found marked general increases in lung IL-6, MIP-2, and MPO in mice deficient for toll-like receptor (TLR-4) or the combined lack of TLR-4/FasL. However, the TLR-4 defect markedly attenuated neutrophil influx into the lung while not altering the change in local cytokine/chemokine expression. Alternatively, the combined loss of FasL and TLR-4 did not inhibit the increase in MPO and exacerbated lung IL-6/MIP-2 levels even further.

Animals↗
PubMed2002

Female sex hormones regulate macrophage function after trauma-hemorrhage and prevent increased death rate from subsequent sepsis.

OBJECTIVE: To determine whether reduction of circulating female sex hormones by ovariectomy causes suppression of macrophage (Mphi) function after trauma-hemorrhage and increases susceptibility to subsequent sepsis. SUMMARY BACKGROUND DATA: Studies indicate that immune functions are markedly depressed in males but not in proestrus females after trauma-hemorrhage. Although male sex steroids are immunosuppressive, it remains unknown whether female sex hormones are immunoprotective after trauma-hemorrhage. METHODS: Circulating female sex hormones were reduced by ovariectomy of 8-week-old female CBA/J mice. Two weeks afterward, ovariectomy and proestrus sham-ovariectomy mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (35 +/- 5 mm Hg for 90 minutes, then resuscitated) or sham operation. Two hours afterward, splenic and peritoneal Mphi and Kupffer cells were isolated and cytokine production was assessed. In a second series of experiments, animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, and survival was assessed. RESULTS: Release of interleukin-1 and interleukin-6 by splenic and peritoneal Mphi from proestrus mice was maintained after trauma-hemorrhage, whereas release of interleukin-1 and interleukin-6 by Mphi from ovariectomized mice was depressed by approximately 50%. In contrast, trauma-hemorrhage resulted in a fourfold increase of Kupffer cell release of tumor necrosis factor-alpha in ovariectomized females and a fivefold increase in plasma concentrations of tumor necrosis factor-alpha. Release of tumor necrosis factor-alpha and plasma concentrations were unchanged in proestrus mice under such conditions. When proestrus and ovariectomized animals were subjected to sepsis by cecal ligation and puncture at 24 hours after trauma-hemorrhage or sham operation, ovariectomized mice had a significantly higher death rate than proestrus mice. CONCLUSIONS: These findings suggest that female sex hormones play a critical role in maintaining immune responses after trauma-hemorrhage by suppressing the elaboration of tumor necrosis factor-alpha and prevent the increased lethality from subsequent sepsis. Thus, female sex hormones may be a useful adjunct in preventing trauma-induced immunodepression and increased susceptibility to subsequent sepsis.

Analysis of Variance↗
PubMed2002

Mechanism of immune dysfunction in sepsis: inducible nitric oxide-meditated alterations in p38 MAPK activation.

BACKGROUND: After the onset of sepsis, there is a marked dysfunction in cell-mediated immunity that contributes to the morbidity and mortality seen in this condition. Although both nitric oxide (NO) from inducible NO synthase (iNOS) and the activation of p38 mitogen-activated protein kinase (p38 MAPK) appear to contribute to this immune dysfunction, the extent to which NO regulates p38 MAPK activity in sepsis remains unknown. METHODS: To examine this, we induced sepsis by cecal ligation and puncture (CLP) in iNOS knockout (iNOS -/-) or C57BL/6 control mice. Twenty-four hours after CLP or sham operation, splenic T cells and macrophages were isolated and then stimulated with monoclonal antibody against the T-cell marker CD3 (anti-CD3) or lipopolysaccharide. At 4 or 24 hours after stimulation, cytokine release was determined by enzyme-linked immunosorbent assay, and p38 MAPK phosphorylation (activation) was determined by immunoblotting with antibody specific to phosphorylated p38 MAPK. RESULTS: Splenic T-cell p38 MAPK activation and interleukin (IL)-10 release was increased by CLP, whereas Th1 cytokine (IL-2, interferon-gamma) release was depressed. iNOS gene deficiency inhibited p38 MAPK activation in splenic T cells taken from septic mice, and also suppressed IL-10 release in both sham and septic mice. Interestingly, although deficiency of iNOS restored IL-2 release after CLP, both sham and CLP T cells remained depressed in their ability to release interferon-gamma. Septic insult markedly suppressed C57BL/6 splenic macrophage release of proinflammatory agents tumor necrosis factor, IL-12, and IL-1, while augmenting the release of IL-10. However, although deficiency of iNOS concomitantly restored the ability to produce tumor necrosis factor while suppressing the rise in IL-10 release and p38 MAPK activation, it only partially restored IL-1 release and had no effect on IL-12 production seen after CLP. CONCLUSION: These data suggest that NO release from iNOS regulates aspects of sepsis-induced immune dysfunction by the activation of p38 MAPK.

Animals↗