The level of hypotension during hemorrhagic shock is a major determinant of the post-resuscitation systemic inflammatory response: an experimental study

<p>Abstract</p> <p>Background</p> <p>To evaluate whether the level of hypotension during hemorrhagic shock may influence the oxidative and inflammatory responses developed during post-ischemic resuscitation.</p> <p>Methods</p> <p>Fifteen rabbits were equally allocated into three groups: sham-operated (group sham); bled within 30 minutes to mean arterial pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30 mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was performed by reinfusing shed blood with two volumes of Ringer's lactate and blood was sampled for estimation of serum levels aminotransferases, creatinine, TNF-α, IL-1β, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS) and for the determination of oxidative burst of polymorhonuclears (PMNs) and mononuclear cells (MCs).</p> <p>Results</p> <p>Serum AST of group shock-30 was higher than that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum creatinine of group shock-30 was higher than group shock-40 at 120 minutes. Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and shock-30 were higher than group sham within the first 60 minutes after start of resuscitation. Serum concentrations of IL-1β, IL-6 and TNF-α of group shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No differences were found between two groups regarding serum MDA and TAS and oxidative burst on PMNs and MCs but both groups were different to group sham.</p> <p>Conclusion</p> <p>The level of hypotension is a major determinant of the severity of hepatic and renal dysfunction and of the inflammatory response arising during post-ischemic hemorrhagic shock resuscitation. These findings deserve further evaluation in the clinical setting.</p

Amyand's hernia-a vermiform appendix presenting in an inguinal hernia: a case series

<p>Abstract</p> <p>Introduction</p> <p>A vermiform appendix in an inguinal hernia, inflamed or not, is known as Amyand's hernia. Here we present a case series of four men with Amyand's hernia.</p> <p>Case presentations</p> <p>We retrospectively studied 963 Caucasian patients with inguinal hernia who were admitted to our surgical department over a 12-year period. Four patients presented with Amyand's hernia (0.4%). A 32-year-old Caucasian man had an inflamed vermiform appendix in his hernial sac (acute appendicitis), presenting as an incarcerated right groin hernia, and underwent simultaneous appendectomy and Bassini suture hernia repair. Two patients, Caucasian men aged 36 and 43 years old, had normal appendices in their sacs, which clinically appeared as non-incarcerated right groin hernias. Both underwent a plug-mesh hernia repair without appendectomy. The fourth patient, a 25-year-old Caucasian man with a large but not inflamed appendix in his sac, had a plug-mesh hernia repair with appendectomy.</p> <p>Conclusion</p> <p>A hernia surgeon may encounter unexpected intraoperative findings, such as Amyand's hernia. It is important to be prepared and apply the appropriate treatment.</p

Skewed Distribution of Circulating Activated Natural Killer T (NKT) Cells in Patients with Common Variable Immunodeficiency Disorders (CVID)

Common variable immunodeficiency disorder (CVID) is the commonest cause of primary antibody failure in adults and children, and characterized clinically by recurrent bacterial infections and autoimmune manifestations. Several innate immune defects have been described in CVID, but no study has yet investigated the frequency, phenotype or function of the key regulatory cell population, natural killer T (NKT) cells. We measured the frequencies and subsets of NKT cells in patients with CVID and compared these to healthy controls. Our results show a skewing of NKT cell subsets, with CD4+ NKT cells at higher frequencies, and CD8+ NKT cells at lower frequencies. However, these cells were highly activated and expression CD161. The NKT cells had a higher expression of CCR5 and concomitantly expression of CCR5+CD69+CXCR6 suggesting a compensation of the remaining population of NKT cells for rapid effector action

Nitrosative and Oxidative Stresses Contribute to Post-Ischemic Liver Injury Following Severe Hemorrhagic Shock: The Role of Hypoxemic Resuscitation

Purpose: Hemorrhagic shock and resuscitation is frequently associated with liver ischemia-reperfusion injury. The aim of the study was to investigate whether hypoxemic resuscitation attenuates liver injury. Methods: Anesthetized, mechanically ventilated New Zealand white rabbits were exsanguinated to a mean arterial pressure of 30 mmHg for 60 minutes. Resuscitation under normoxemia (Normox-Res group, n = 16, PaO2 = 95–105 mmHg) or hypoxemia (Hypox-Res group, n = 15, PaO 2 = 35–40 mmHg) followed, modifying the FiO 2. Animals not subjected to shock constituted the sham group (n = 11, PaO 2 = 95–105 mmHg). Indices of the inflammatory, oxidative and nitrosative response were measured and histopathological and immunohistochemical studies of the liver were performed. Results: Normox-Res group animals exhibited increased serum alanine aminotransferase, tumor necrosis factor- alpha, interleukin (IL)-1b and IL-6 levels compared with Hypox-Res and sham groups. Reactive oxygen species generation, malondialdehyde formation and myeloperoxidase activity were all elevated in Normox-Res rabbits compared with Hypox-Res and sham groups. Similarly, endothelial NO synthase and inducible NO synthase mRNA expression was up-regulated and nitrotyrosine immunostaining increased in animals resuscitated normoxemically, indicating a more intense nitrosative stress. Hypox-Res animals demonstrated a less prominent histopathologic injury which was similar to sham animals. Conclusions: Hypoxemic resuscitation prevents liver reperfusion injury through attenuation of the inflammatory respons

Cerebrospinal fluid of patients administered moxifloxacin modulates the secretion of cytokines from human monocytes

To evaluate the ex vivo immunomodulatory properties of moxifloxacin, we applied serum and cerebrospinal fluid (CSF) samples from 50 patients who received a single oral dose of 400 mg. Patients were divided into 5 groups according to time lapsing between sampling and drug intake: group I, 0.5 to 1 h; group II, 1 to 2 h; group III, 2 to 4 h; group IV, 4 to 6 h; and group V, 6 to 8 h. Samples were added to cultures of U937 monocytes stimulated by 10 ng/mL of lipopolysaccharide (LPS) and 1 × 105 colony-forming unit (CFU) of 1 heat-killed penicillin-resistant isolate of Streptococcus pneumoniae. Concentrations of cytokines were estimated in supernatants. Concentrations of interleukin (IL)-1β, IL-10, and IL-12 released after stimulation by LPS were significantly decreased by CSF of groups I, IV, and V. After stimulation by the heat-killed isolate, concentrations of tumor necrosis factor α (TNF-α), IL-1β, IL-6, and IL-10 were increased in the presence of CSF of group III; those of IL-12p70 were decreased by CSF of groups I and II. Concentrations of IL-1β, IL-6, and IL-8 drawn after stimulation by LPS were significantly decreased upon addition of serum from all groups. After stimulation by the heat-killed isolate, concentrations of TNF-α were decreased by serum drawn from all patients; IL-1β was increased after addition of serum of groups I, II, and V. It is concluded that CSF and serum of patients administered moxifloxacin may effectively modulate the production of pro- and anti-inflammatory cytokines by human monocytes. These results render new perspectives for the therapy for meningitis. © 2008 Elsevier Inc. All rights reserved

Longitudinal assessment of adrenal function in the early and prolonged phases of critical illness in septic patients: Relations to cytokine levels and outcome

Context: Adrenal dysfunction remains a controversial issue in critical care. The long-stay intensive care unit (ICU) population may be at increased risk of adrenal insufficiency. Objective: We aimed to determine whether adrenal dysfunction develops during the course of sepsis. Design: This is a prospective observational longitudinal study. Setting: The study was conducted in the ICU of a secondary/tertiary care hospital Patients: We studied 51 consecutive mechanically ventilated patients with sepsis. Intervention: We measured cortisol, ACTH, cortisol-binding globulin, cytokines, and cortisol 30 minutes after 1 μg ACTH(1-24), upon sepsis diagnosis and every 3 to 4 days, until Day 30 or until recovery or death. Main Outcome Measures: We looked for changes in baseline and stimulated cortisol levels and its relationship to ACTH levels, sepsis severity or survival. Results: Base line and stimulated cortisol levels did not vary significantly. Septic patients with shockhad higher baseline (20 ± 6 vs 17 ± 5 μg/dL, P = .03) and stimulated cortisol levels (26 ± 5 vs 23 ± 6 μg/dL, P = .04), compared with those without shock. On Day 1, ACTH levels could not predict cortisol levels (R2 = 0.06, P = .08). ACTH levels increased significantly after Day 10 and, at this time point, they related to cortisol levels (R2 = 0.35, P &amp;lt; .001). Development of septic shock, or resolution from it, was not associated with changes in baseline, stimulated cortisol levels, or the cortisol increment. There was much inpatient variability in the diagnosis of adrenal dysfunction at different time points. Conclusions: Total cortisol levels relate both to the severity and outcome of sepsis and remain fairly unchanged during the course of illness. Initially, cortisol levels are largely ACTH independent, whereas ACTH increases and correlates with cortisol levels later on. Adrenal dysfunction does not seem to be a major problem during the prolonged phase of sepsis. Although not significant, the variation in cortisol levels may be such that classification of patients varies, questioning the utility of arbitrary cut-offs to define adrenal dysfunction in septic patients. Copyright © 2014 by the Endocrine Society

Diffuse intraabdominal desmoplastic small round cell tumor: A ten-year experience

Background: Intraabdominal desmoplastic small round cell tumors (IDSRCT) are rare in children and predominantly affect male adolescents and young adults. We present our experience in the management of five children with diffuse IDSRCT, managed with aggressive chemotherapy, surgery, radiotherapy and peripheral blood stem cell transplantation. Material and Methods: During the last decade five patients, four males and one female (mean age 9.6 years), with diffuse IDSRCT were managed in our department. The main symptoms were abdominal distention, vague abdominal pain, and vomiting. Three patients with inoperable tumor on admission were submitted initially to open biopsy followed by aggressive chemotherapy. Regression of the tumor was followed by a second laparotomy and radical excision of any macroscopically distinguishable masses, followed by chemotherapy. In the remaining two patients a debulking procedure was done initially, followed by chemotherapy. The accurate diagnosis of the disease was established by immunohistochemistry, additionally confirmed in the last two patients by molecular analysis. Results: Three patients who had radical excision of the tumor and adjuvant chemotherapy had recurrence after two to six months. In the remaining two patients, recurrence was evident after two and eighteen months, respectively, following debulking. in addition, one patient with recurrence received radiotherapy and two others underwent peripheral blood stem cell transplantation. All but one patient died within three years from diagnosis. The last patient, who was submitted to a debulking procedure, is still alive eight months after the operation. Conclusions: Intrabdominal desmoplastic small round cell tumor is a highly aggressive malignancy with a very poor prognosis. Multiagent chemotherapy usually leads initially to a temporary regression of the tumor, but recurrence is the rule. Radical surgical excision, radiotherapy and peripheral blood stem cell transplantation does not seem to improve prognosis significantly. Despite all therapeutic modalities the outcome is dismal and surgical efforts can be considered only as palliative

Hypoxemic resuscitation after hemorrhagic shock is accompanied by reduced serum levels of angiopoietin-2

Background: To investigate whether angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) are implicated in the hypoxemic resuscitation from hemorrhagic shock. Methods: Twenty rabbits were subjected to hemorrhagic shock after blood exsanguination; resuscitation was performed by infusion of the shed blood in ten rabbits under normoxemic conditions (NormoxRes) and in 10 under hypoxemic conditions (HypoxRes); four rabbits were subjected to sham operation. Serum was drawn at serial time intervals: serum was applied for stimulation of U937 monocytes. Results: Serum concentrations of Ang2 were higher in the NormoxRes group compared to the HypoxRes group at 90 min (p: 0.049) and at 120 min (p: 0.028). Serum concentrations of VEGF did not differ between groups. Concentrations of VEGF in the supernatants of U937 stimulated with sera of all groups were below detection limit The wet to dry. lung ratio of the HypoxRes group was significantly lower than the NormoxRes group (p &lt; 0.0001). Conclusions: Hypoxemic resuscitation from hemorrhagic shock is a process accompanied by reduced serum levels of Ang2. These findings add significantly to our understanding of that experimental treatment strategy of resuscitation. (C) 2009 Elsevier Ltd. All rights reserved

Hypoxemic resuscitation prevents pulmonary capillary endothelial dysfunction induced by normoxemic resuscitation from hemorrhagic shock

OBJECTIVE:: Hypoxemic reperfusion attenuates brain injury secondary to severe cerebral ischemia, myocardial, and intestinal injury occurring in intestinal postischemic shock, and offers hemodynamic stabilization and attenuation of inflammatory response when applied in the resuscitation from hemorrhagic shock. In this study, we sought to investigate the effect of hypoxemic resuscitation on pulmonary endothelium. DESIGN:: Prospective, randomized, controlled animal study. SETTING:: Experimental laboratory of a university intensive care unit. SUBJECTS:: Male New Zealand White rabbits weighting 3-3.5 kg. INTERVENTIONS:: Hemorrhagic shock at mean arterial pressure of 40 mm Hg was induced by exsanguinations in anesthetized, mechanically ventilated animals for 60 minutes and thereafter rabbits were resuscitated by homologous blood and Ringer&apos;s lactate infusion under normoxemia (Normox-Res group, Pao2 = 95-105 mm Hg, n = 9) or hypoxemia (Hypox-Res group, Pao2 = 35-40 mm Hg, n = 7). MEASUREMENTS AND MAIN RESULTS:: Using indicator-dilution techniques we measured at baseline and post resuscitation pulmonary capillary endothelial angiotensin converting enzyme activity expressed as percentage of metabolism (%M) and hydrolysis (v) of the substrate H-benzoyl-Phe-Ala-Pro. Normox-Res rabbits exhibited decreased %M (p &lt; 0.05) and v (p &lt; 0.05) post resuscitation as compared with baseline, while no differences occurred in the Hypox-Res group. Myeloperoxidase was measured in lung tissue and was higher in Normox-Res than Hypox-Res animals (p &lt; 0.01). Lung injury was estimated microscopically, whereas the expression of the intercellular adhesion molecule-1 and the vascular cell adhesion molecule-1 were assessed by immunohistochemistry on sections coming from the same tissue block. Compared with Normox-Res, Hypox-Res animals exhibited lower lung injury histopathological score (p &lt; 0.01) and lung malondialdehyde concentration (p &lt; 0.01), and lower intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expressions in both the inflammatory cells (p &lt; 0.01) and the blood vessels (p &lt; 0.05). CONCLUSIONS:: Normoxemic resuscitation of hemorrhagic shock is associated with pulmonary endothelial dysfunction and lung injury that may be attenuated by hypoxemic resuscitation. © 2009 by the Society of Critical Care Medicine and Lippincott Williams &amp; Wilkins