The emerging role of MIF in septic shock and infection

A case of successful patch angioplasty for the right coronary artery (RCA) orifice dissection following selective coronary perfusion is reported. A 56-year-old woman who had mitral restenosis, aortic stenosis, and atrial fibrillation with bradycardia-tachycardia syndrome was referred to our hospital for operation. The operation, which contained aortic valve replacement and mitral commissurotomy, was performed with hypothermic cardiopulmonary bypass and crystalloid cardioplegic arrest. The ascending aorta was opened, and selective coronary perfusion was performed. The right coronary cannula was difficult to insert and dislodged several times. At the second infusion of the cardioplegic solution, the right coronary orifice and ascending aortic wall was dissected. The dissection extended to the proximal RCA. The aortotomy was extended into the RCA beyond its orifice. The Xenomedica pericardial patch was used to enlarge the diameter of the RCA with closing the dissected cavity. Then the patch was brought onto the side of the aorta and the aortotomy was closed in the usual manner. Post operative coronary angiography revealed widely patent RCA orifice and good runoff. Two years after operation the patient is free of angina with unlimited physical activity.     

The pathogenesis of septic shock

A new age of treating patients with septic shock is rapidly approaching. A multidrug approach will likely be used to interrupt the systemic inflammatory response to infection, with use of new immune and inflammatory modulating therapies. In this article are reviewed the advances made in understanding the cellular events that cause septic shock. Critical care nurses need to update themselves on this new information to provide optimal care that patients with septic shock demand. Symptoms of septic shock, its hemodynamic characteristics, and the actions of principal inflammatory mediators that cause vasodilation and capillary leak are discussed.     

Antiendotoxin therapies for septic shock

Gram-negative shock is thought to result primarily from the effects of endotoxin, a component of the bacterial outer membrane. Accordingly, therapies aimed at inhibiting, neutralizing, or clearing endotoxin have been extensively explored. Despite over 30 years of research, no antiendotoxin approach to the treatment of human septic shock is of proven benefit. In recent randomized clinical trials of monoclonal antibodies against endotoxin, therapeutic efficacy was not convincingly demonstrated. This result, however, does not eliminate the possibility that other antiendotoxin therapies may be effective. The antibodies used in these clinical trials do not appear to neutralize endotoxin in vitro and are not reproducibly protective in animal models of sepsis. Newer agents with well-defined mechanisms of antiendotoxin activity may help clarify the role of endotoxin in septic shock and prove useful therapy for some patients.     

The ursodeoxycholic acid-p-aminobenzoic acid test in the diagnosis of small bowel bacterial overgrowth syndrome

Contaminated small bowel syndrome is frequently associated with meteorism due to excessive gas formation, and diarrhoea as a result of bacterial fermentative processes, including splitting of carbohydrates or deconjugating and dehydroxylating bile salts. In addition to gas production, bacteria capable of metabolizing bile salts have been shown to release p-aminobenzoic acid (PABA) from and Ursodeoxycholic-acid-PABA substrate. Our aim was to determine the possible complementary role of the UDCA-PABA test in the diagnosis of bacterial overgrowth. PATIENTS AND METHODS: The H2 breath and UDCA-PABA tests were performed simultaneously on 46 patients with suspected contaminated small bowel syndrome, and on 7 healthy subjects. The H2 breath test was performed by oral loading of 25 g lactose and/or 10 g lactulose. The UDCA-PABA test was carried out by determining urinary excretion of PABA after oral loading with 250 mg UDCA-PABA conjugate. The diagnosis of bacterial overgrowth was established, when either H2 breath, or UDCA-PABA test proved to be pathological. RESULTS: Based upon the pathologic values of either the H2 breath test, or the UDCA-PABA test, 25 out of 46 patients proved to have contaminated small bowel syndrome. In 10 out of 25 patients only pathologic urinary PABA excretion (12.772 +/- 1.707 vs 4.1 +/- 0.58), indicated bacterial overgrowth, and in 9 out of the same group only positive H2 breath test (early rise of > 20 ppm of H2) indicated the same, while in 6 cases both tests proved to be pathological. In 7 CSBS patients the urinary excretion of PABA significantly decreased following a 10 day Tinidazole treatment (5.48 +/- 1.286 vs 13.068 +/- 2.068). CONCLUSION: The UDCA-PABA test proved to be a valuable complementary method to detect bacterial overgrowth, when H2 production failed to reveal bacterial overgrowth.     

Staphylococcus aureus-induced septic arthritis and septic death is decreased in IL-4-deficient mice: role of IL-4 as promoter for bacterial growth

Lack of IL-4 has been shown to be protective in some experimental models of infectious diseases in mice such as cutaneous leishmaniasis. At the same time IL-4, together with other Th2 cytokines, including IL-10 and IL-13, is known as an anti-inflammatory cytokine with the potential to down-regulate proinflammatory cytokine production. To investigate the role of IL-4 in experimental Staphylococcus aureus-induced and T lymphocyte-mediated arthritis, IL-4-deficient C57BL/6 mice (IL-4(-/-)) and their congenic controls (IL-4(+/+)) were inoculated with a toxic shock syndrome toxin-1-producing S. aureus strain. In IL-4(+/+) mice, arthritis peaked 14 days after bacterial inoculation, whereas, at that time, IL-4(-/-) mice displayed significantly less frequent (p < 0.05) joint inflammation. Paralleling lower frequency of arthritis, IL-4-deficient mice showed a decreased bacterial burden in joints (p = 0.014) and kidneys (p = 0.029), as well as lower infection-triggered weight decrease and mortality. In vitro, IL-4 inhibited intracellular killing of S. aureus in infected macrophages, without affecting phagocytosis. This finding may explain the enhanced staphylococcal clearance observed in IL-4(-/-) mice in vivo. Our results suggest that IL-4 and IL-4-dependent Th2 responses promote septic arthritis and sepsis-related mortality by inhibition of bacterial clearance during S. aureus infection.     

The role of small bowel follow-through examination in the diagnosis of coeliac disease

A retrospective study of 105 barium follow-through examinations on 102 patients suspected of having malabsorption syndrome has been carried out to assess the usefulness of this technique in the diagnosis of coeliac disease. Comparison with histological and biochemical data has been made. Of the 34 examinations on 31 patients with a proven diagnosis of coeliac disease, 30 examinations showed both abnormal X-ray and biopsy findings, two examinations showed normal X-ray appearance but abnormal jejunal biopsy and two showed normal jejunal histology but abnormal X-ray findings. There were two cases with sensitivity, non-invasive nature, ease and cheapness of the technique, barium follow-through examination is suggested as the initial investigation in patients suspected of coeliac disease.     

Antibiotic-induced release of bacterial cell wall components in the pathogenesis of sepsis and septic shock: a review

This article reviews the new criteria for selecting the proper antimicrobial agent and dosage regimen for standard treatment of severe sepsis, with the intention of preventing septic shock. After introducing new concepts on the pathogenesis of sepsis and septic shock, the authors analyze the parameters of betalactam antibacterial activity, the antibiotic-induced release of bacterial endotoxin and the interrelationships between pharmacokinetics and pharmacodynamics of antibiotics in the search for an optimum dosage regimen of antimicrobial mono- or polytherapy for severely ill septic patients admitted to the intensive care unit.     

Emerging therapies for sepsis and septic shock

OBJECTIVE: To define the distribution of neuroendocrine (NE) cells in the different compartments of the verumontanum (utricle, ejaculatory ducts, main prostatic ducts) in relation to other areas of the prostate. MATERIALS AND METHODS: A retrospective study was conducted of 30 radical prostatectomy specimens processed in toto as whole-mount sections. Among these cases, 15 patients had received a preoperative short course of total androgen blockade. The distribution and number of NE cells in the prostatic utricle and in normal areas of the prostate were analysed using chromogranin A (CgA) and serotonin immunohistochemistry; prostate-specific antigen (PSA) immunostaining was performed systematically on a consecutive section. Six cases of endometrioid carcinomas were also investigated using these methods. The vascularization of the verumontanum was assessed by factor VIII immunohistochemistry and examined in relation to vascular endothelial growth factor (VEGF) immunohistochemistry. RESULTS: There were significantly more NE cells in the prostatic utricle than in the main prostatic ducts of the verumontanum and the peripheral prostatic acini. In the ejaculatory ducts. there were NE cells only in the extreme distal portion. Cells immunoreactive for PSA were present at the level of the utricle and the extreme distal portion of the ejaculatory ducts. The distribution, number and shape of NE cells were unaltered by hormonal treatment. NE cells of the verumontanum were positive for VEGF expression. Factor VIII detected more vessels around the utricle and ejaculatory ducts. NE cells (positive for CgA and serotonin) were observed in three cases of endometrioid carcinoma. CONCLUSION: The high concentration of NE cells found in the prostatic utricle suggests a possible role for these cells in human fertility. Moreover, neuroendocrine differentiation in endometrioid (large duct) carcinoma, documented for the first time, supports the concept that this cancer type is a variant of a conventional adenocarcinoma.     

Norepinephrine or dopamine for the treatment of hyperdynamic septic shock?

STUDY OBJECTIVE: To compare the ability of dopamine and norepinephrine to reverse hemodynamic and metabolic abnormalities of human hyperdynamic septic shock. DESIGN: Prospective, double-blind, randomized trial. SETTING: An ICU in a university hospital. PATIENTS: Adult patients with hyperdynamic septic shock after fluid resuscitation. INTERVENTIONS: Patients were assigned to receive either dopamine (2.5 to 25 micrograms/kg/min) or norepinephrine (0.5 to 5.0 micrograms/kg/min). If hemodynamic and metabolic abnormalities were not corrected with the maximum dose of one drug, the other was added. MEASUREMENTS AND RESULTS: The aim of therapy was to achieve and maintain for at least 6 h all of the following: (1) systemic vascular resistance index > 1,100 dynes.s/cm5.m2 and/or mean systemic blood pressure > or = 80 mm Hg; (2) cardiac index > or = 4.0 L/min/m2; (3) oxygen delivery > 550 ml/min/m2; and (4) oxygen uptake > 150 ml/min/m2. With the use of dopamine 10 to 25 micrograms/kg/min, 5 of 16 patients (31 percent) were successfully treated, as compared with 15 of 16 patients (93 percent) by norepinephrine at a dose of 1.5 +/- 1.2 micrograms/kg/min (p < 0.001). Ten of 11 patients who did not respond to dopamine and remained hypotensive and oliguric were successfully treated with the addition of norepinephrine. CONCLUSIONS: At the doses tested, norepinephrine was found, in the present study, to be more effective and reliable than dopamine to reverse the abnormalities of hyperdynamic septic shock. In the great majority of the study patients, norepinephrine was able to increase mean perfusing pressure without apparent adverse effect on peripheral blood flow or on renal blood flow (since urine flow was reestablished). At the same time, oxygen uptake was increased.     

Treatment of septic shock with immunotherapy

Sepsis is the thirteenth leading cause of death in the United States. Despite increased knowledge about its pathophysiology, availability of powerful antibiotics, and advanced diagnostic and monitoring techniques, mortality rates have not changed significantly over the past 30 years. Immunotherapy may improve outcome in the critically ill with sepsis, although trial results have been disappointing to date.     

The effects of intravenous antioxidants in patients with septic shock

Oxidative stress is implicated in septic shock. We investigated the effect of intravenous antioxidant therapy on antioxidant status, lipid peroxidation, hemodynamics and nitrite in patients with septic shock. Thirty patients randomly received either antioxidants (n-acetylcysteine 150 mg/kg for 30 min then 20 mg/kg/h plus bolus doses of 1 g ascorbic acid and 400 mg alpha-tocopherol) or 5% dextrose. Basal vitamin C was low and redox-reactive iron was elevated in all patients. In the 16 patients receiving antioxidants, vitamin C increased (p = .0002) but total antioxidant capacity was unaffected. Lipid peroxides were elevated in all patients but did not increase further in the patients receiving antioxidants. Plasma total nitrite also increased (p = .007) in the antioxidant group. Heart rate increased in patients receiving antioxidants at 60 min (p = .018) and 120 min (p = .004). Cardiac index also increased at 60 min (p = .007) and 120 min (p = .05). Systemic vascular resistance index decreased at 120 min in the antioxidant treated patients (p = .003). The effect of antioxidants on hemodynamic variables has not previously been reported. Antioxidant administration may be a useful adjunct to conventional approaches in the management of septic shock.     

The small bowel enema in children: a description of a technique

A technique for performing small bowel enemas in children is described in detail and the results of using this technique reported. Minor modifications are necessary to the technique commonly used in adults; a softer tube is used and sedation given early and generously. It is stressed that the radiologist must control the sedation as well as the radiology.     

Diagnosis of small intestinal bacterial overgrowth in clinical praxis: a comparison of the culture of small bowel aspirate, duodenal biopsies and gastric aspirate

BACKGROUND/AIMS: This study was undertaken to validate the usefulness of the culture of duodenal biopsy specimens and gastric aspirate compared to the culture of small bowel aspirate for diagnosing small intestinal bacterial overgrowth. We also investigated the occurrence of predisposing conditions in these patients. METHODOLOGY: Seventy five consecutive patients, admitted because of symptoms which caused us to suspect small intestinal bacterial overgrowth, were studied. For all patients, specimens for the culture of small bowel aspirate, duodenal biopsies and gastric aspirate were obtained during upper endoscopy. RESULTS: Eighteen patients showed growth of gram negative bacteria, 22 growth of gram positive bacteria and 35 showed no significant growth in cultures of small bowel aspirate. Cultures of duodenal biopsies revealed gram negative bacteria in 11 patients, gram positive bacteria in 9 and no growth in 55. Cultures of gastric aspirate revealed gram negative bacteria in 7 patients, gram positive bacteria in 12 and no growth in 51. Ten of the 18 patients with gram negative overgrowth and 13 of the 22 patients with gram positive overgrowth had a predisposing condition. In contrast, only 4 of the 35 without overgrowth had a predisposing condition. CONCLUSIONS: The culture of duodenal biopsy specimens or gastric aspirate is a less sensitive method than the culture of small bowel aspirate. Most patients with culture-proven small intestinal bacterial overgrowth had at least one predisposing condition.     

Primary small bowel lymphoma manifested as obstructive jaundice in a patient with AIDS

We describe a patient with acquired immunodeficiency syndrome (AIDS) and non-Hodgkin's lymphoma of the duodenum manifested as obstructive jaundice. Endoscopic retrograde cholangiography led to the diagnosis and was used to relieve the obstruction. The patient received chemotherapy and is in remission 21 months after the diagnosis, thus justifying an aggressive approach toward diagnosis and treatment in this patient population.     

Has the mortality of septic shock changed with time

OBJECTIVES: To determine whether a systematic review of the literature could identify changes in the mortality of septic shock over time. DATA SOURCES: A review of all relevant papers from 1958 to August 1997, identified through a MEDLINE search and from the bibliographies of articles identified. DATA SYNTHESIS: The search identified 131 studies (99 prospective and 32 retrospective) involving a total of 10,694 patients. The patients' mean age was 57 yrs with no change over time. The overall mortality rate in the 131 studies was 49.7%. There was an overall significant trend of decreased mortality over the period studied (r=.49, p < .05). The mortality rate in those patients with bacteremia as an entry criterion was greater than that rate in patients whose entry criterion was sepsis without definite bacteremia (52.1% vs. 49.1%; chi2=6.1 and p< .05). The site of infection altered noticeably over the years. Chest-related infections increased over time, with Gram-negative infections becoming proportionately less common. If all other organisms and mixed infections are included with the Gram-positives, the result is more dramatic, with these organisms being causative in just 10% of infections between 1958 and 1979 but in 31% of infections between 1980 and 1997. CONCLUSIONS: The present review showed a slight reduction in mortality from septic shock over the years, although this result should be approached with caution. The heterogeneity of the articles and absence of a severity score for most of the studies limited our analysis. Furthermore, there was an increasing prevalence of Gram-positive causative organisms, and a change of the predominant origin of sepsis from the abdomen to the chest.     

Vasopressin deficiency and vasodilation of septic shock

An 83-year-old woman with previous closed transventricular commissurotomy was admitted for congestive heart failure. Echocardiogram and angiography demonstrated a mitral restenosis and a large-mouthed false aneurysm of the left ventricle.