Noninfectious Inflammatory Processes Research Articles

Suppurative lymphadenitis

Suppurative lymphadenitis is an important and common form of soft tissue infection. Most acute cases of suppurative lymphadenitis are caused by Staphylococcus aureus or by Streptococcus pyogenes. Empiric antibiotic therapy is frequently successful in the early stages of the disease process, but increasing prevalence of methicillin-resistant S. aureus in particular has necessitated a shift in antibiotic choice that is dictated primarily by specific local resistance patterns. Several other organisms and noninfectious inflammatory processes may give rise to a clinical syndrome suggestive of suppurative lymphadenitis. Failure to respond to empiric antibiotics should trigger a diagnostic re-evaluation to determine the need for surgical intervention and/or the possibility of alternative microbiologic diagnoses.

Anatomical repair of a congenital aneurysm of the distal abdominal aorta in a newborn

Congenital (primary) neonatal abdominal aortic aneurysm (AAA) is an extremely rare truncular arterial abnormality among numerous congenital vascular malformations. Only seven cases have been reported as congenital origin in newborns. This report presents the case of a male infant in whom a 33-mm congenital AAA was diagnosed prenatally and was successfully treated 10 days after birth without exogenous graft material or aneurysmorrhaphy. Follow-up study at 39 months demonstrated excellent clinical, ultrasound scan, and computed tomography scan findings. Anatomic reconstruction with native vessels is the preferred surgical technique to ensure the child's potential for harmonious growth.

Potential clinical utility of dual time point FDG-PET for distinguishing benign from malignant lesions: implications for oncological imaging

The utility of 18F-fl uorodeoxyglucose (FDG)-positron emission tomography (PET) is widely recognized for the management of patients with cancer encompassing several aspects including diagnosis, staging, and monitoring therapeutic intervention1. However, FDG not only accumulates within malignant tumor sites but also in the infl ammatory lesions. As a result, the clinical utility of FDG-PET is also being investigated for detection, characterization, and monitoring of patients with infectious and non-infectious infl ammatory processes in several centres across the world. Functional imaging, in certain settings, has superior diagnostic performance characteristics compared with those of structural imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI). For example, FDG-PET has been shown to be highly sensitive in the detection of chronic osteomyelitis, infection of implanted prostheses, the source of fever of unknown origin, vasculitis, infl ammatory bowel disease, and atherosclerosis2. However, non-specifi c accumulation of FDG in benign processes such as infl ammation and infection can make it diffi cult at times to distinguish malignant neoplastic lesions from the benign ones. Fortunately, dual time point and delayed FDG-PET imaging allows for distinction between these two distinct pathological categories, as the pattern and rate of FDG uptake over time vary considerably between malignant and benign processes. Hence, dual time point FDG-PET has gained considerable interest in the recent literature as an important diagnostic approach to improve the overall sensitivity, specifi city, and accuracy of FDG-PET3

Novel critical role of Toll-like receptor 4 in lung ischemia-reperfusion injury and edema

Toll-like receptors (TLRs) of the innate immune system contribute to noninfectious inflammatory processes. We employed a murine model of hilar clamping (1 h) with reperfusion times between 15 min and 3 h in TLR4-sufficient (C3H/OuJ) and TLR4-deficient (C3H/HeJ) anesthetized mice with additional studies in chimeric and myeloid differentiation factor 88 (MyD88)- and TLR4-deficient mice to determine the role of TLR4 in lung ischemia-reperfusion injury. Human pulmonary microvascular endothelial monolayers were subjected to simulated warm ischemia and reperfusion with and without CRX-526, a competitive TLR4 inhibitor. Functional TLR4 solely on pulmonary parenchymal cells, not bone marrow-derived cells, mediates early lung edema following ischemia-reperfusion independent of MyD88. Activation of MAPKs and NF-kappaB was significantly blunted and/or delayed in lungs of TLR4-deficient mice as a consequence of ischemia-reperfusion injury, but edema development appeared to be independent of activation of these signaling pathways. Pretreatment with a competitive TLR4 inhibitor prevented edema in vivo and reduced actin cytoskeletal rearrangement and gap formation in pulmonary microvascular endothelial monolayers subjected to simulated warm ischemia and reperfusion. In addition to its well-accepted role to alter gene transcription, functioning TLR4 on pulmonary parenchymal cells plays a key role in very early and profound pulmonary edema in murine lung ischemia-reperfusion injury. This may be due to a novel mechanism: regulation of endothelial cell cytoskeleton affecting microvascular endothelial cell permeability.

The Increased Expression of TREM-1 on Monocytes Is Associated With Infectious and Noninfectious Inflammatory Processes

Inflammation is the response of an organism to tissue injury or infection. It is usually limited to the affected tissue, but sometimes the inflammatory mediators reach the bloodstream and act systemically. A compensatory anti-inflammatory response syndrome, in which expression of major histocompatibility complex class II (MHC-II) molecules are decreased, regulates the resulting systemic inflammatory response syndrome (SIRS). SIRS and compensatory anti-inflammatory response syndrome can lead to the development of sepsis. Triggering receptor expressed on myeloid cells (TREM)-1 has been proposed as a biomarker of the presence of sepsis. In this study, we investigated whether TREM-1 is increased only in septic patients, and not in patients with systemic inflammatory response but no infection. We also looked for a possible correlation between TREM-1 and MHC-II expression levels and the patients' progress. Fifty-eight surgical patients, 14 septic patients and 50 healthy volunteers, were included in this study. TREM-1 and MHC-II expression on blood monocytes was determined by flow cytometry. TREM-1 expression was increased in all patients after surgery, and its expression was higher in patients with preexisting SIRS. No association was found with the presence of infection. In septic patients, the increase in TREM-1 expression was transitory. MHC-II expression was decreased in both surgical and septic patients, and this decrease was greater in patients with a worse outcome. Increased TREM-1 expression on monocytes is associated with both infectious and noninfectious inflammatory processes, and the levels of MHC-II expression is better correlated with the patient outcome.

Sacroiliíte: avaliação por imagem

Sacroiliíte é o processo inflamatório não-infeccioso das articulações sacroilíacas, sendo critério diagnóstico das espondiloartropatias soronegativas. O diagnóstico desta enfermidade requer confirmação pelos métodos de imagem. O presente trabalho faz um revisão de casos do arquivo didático e de artigos da literatura para ilustrar a anatomia, a técnica e os principais achados de imagem na radiografia, tomografia computadorizada e ressonância magnética, na determinação do diagnóstico de sacroiliíte, abordando inclusive os seus principais diagnóstico diferenciais.

Streptococcus pneumoniae Sheds Syndecan-1 Ectodomains through ZmpC, a Metalloproteinase Virulence Factor

Several microbial pathogens stimulate the ectodomain shedding of host cell surface proteins to promote their pathogenesis. We reported previously that Pseudomonas aeruginosa and Staphylococcus aureus activate the ectodomain shedding of syndecan-1 and that syndecan-1 shedding promotes P. aeruginosa pathogenesis in mouse models of lung and burned skin infections. However, it remains to be determined whether activation of syndecan-1 shedding is a virulence mechanism broadly used by pathogens. Here we show that Streptococcus pneumoniae stimulates syndecan-1 shedding in cell culture-based assays. S. pneumoniae-induced syndecan-1 shedding was repressed by peptide hydroxamate inhibitors of metalloproteinases but not by inhibitors of intracellular signaling pathways previously found to be essential for syndecan-1 shedding caused by P. aeruginosa, S. aureus, or other shedding agonists. A 170-kDa protein fraction with a peptide hydroxamate-sensitive shedding activity was purified by ammonium sulfate precipitation, DEAE chromatography, and size exclusion chromatography. Mass spectrometry analyses revealed that the 170-kDa fraction is composed of ZmpB and ZmpC, two metalloproteinase virulence factors of S. pneumoniae. Both the purified 170-kDa ZmpB/ZmpC fraction and unfractionated S. pneumoniae culture supernatant generated syndecan-1 ectodomains that are smaller than those released by endogenous shedding. Further, a mutant S. pneumoniae strain deficient in zmpC, but not zmpB, lost its capacity to stimulate syndecan-1 shedding. These data demonstrate that S. pneumoniae directly sheds syndecan-1 ectodomains through the action of ZmpC.

Neutrophil serine proteases: specific regulators of inflammation

Neutrophils are essential for host defence against invading pathogens. They engulf and degrade microorganisms using an array of weapons that include reactive oxygen species, antimicrobial peptides, and proteases such as cathepsin G, neutrophil elastase and proteinase 3. As discussed in this Review, the generation of mice deficient in these proteases has established a role for these enzymes as intracellular microbicidal agents. However, I focus mainly on emerging data indicating that, after release, these proteases also contribute to the extracellular killing of microorganisms, and regulate non-infectious inflammatory processes by activating specific receptors and modulating the levels of cytokines.

Diagnostic des pneumopathies acquises sous ventilation mécanique

Two strategies are available for the diagnosis and therapeutic management of ventilator-associated pneumonia (VAP). One based on clinical evaluation (also called noninvasive strategy) is safe, cheap and easy to use. However, this approach obviously leads to an excessive use of antibiotics due to the treatment of signs and symptoms suggesting lung infection, but frequently due to other infections or non-infectious inflammatory process. A microbiological strategy (or invasive) based on direct examination of protected brush or brochoalveolar lavage specimens obtained via a fiberoptic bronchoscopy permits to accurately select patients with VAP with a rapid identification of organisms responsible for infection. This strategy allowing the reduction of unnecessary antimicrobial regiments has been proven to be efficient.

Prevalence of bacteria in the nipple discharge of patients with duct ectasia

The aim of this study was to identify the aerobic and the anaerobic microorganisms which can be related to duct ectasia. The patients were divided into two groups. Group 1 comprised 100 patients with coloured nipple discharge (duct ectasia group), and Group 2 (the control group) was composed of 50 patients without nipple discharge. The culture media used were BHI-PRAS, blood agar, mannitol agar and MacConkey agar. There was a high frequency of bacterial growth in the two groups: 85% in Group 1 and 88% in Group 2. The most prevalent bacteria were Staphylococcus aureus and Staphylococcus epidermidis. There was a statistically significant higher rate of smokers in the duct ectasia group compared with the control group, 25 (25%) patients vs. 5 (10%), respectively (p = 0.03). These findings allow us to put forth the hypothesis that the genesis of duct ectasia may be a non-infectious inflammatory process.

The diagnosis and treatment of infectious vaginitis.

Inflammation of the vagina as a result of infectious agents is very common, both as an overgrowth of normal or common colonizers, or as a frank infection. The most common causes of infectious vaginitis are yeast, bacteria, protozoa, viruses, and parasites. Infections of the vagina produce an increase in vaginal secretion, vulvar symptoms of itching or irritation from contact with irritating vaginal fluid, and sometimes odor. A careful microscopic examination of vaginal secretions generally yields the correct diagnosis, but atypical or recalcitrant disease deserves a confirmatory culture, as noninfectious inflammatory processes can produce similar symptoms.

The contribution of aqueous humor cytology in the differential diagnosis of anterior uvea inflammations

Background:Cytology of the aqueous humor can confirm the diagnosis of many intraocular conditions by revealing inflammatory cells, ghost red cells, lens material, and microorganisms. Purpose:The purpose of this study was to emphasize the contribution of aqueous humor fine needle aspiration cytology in cases where there is a clinical diagnostic dilemma whether an infectious or a noninfectious inflammatory process of the uvea is present. Methods:Collection of 0.15–0.2 ml aqueous humor was carried out with an insulin needle. The aspirated aqueous was then prepared for examination using either the Cytospin or the Thin-Prep technique and smears were stained with modified Papanikolaou and May-Grünwald-Giemsa stains. Results:Cytology of the aqueous humor essentially facilitated the differential diagnosis in 16 cases with an anterior uveal inflammation clinical picture. The cases included phacoanaphylactic endophthalmitis (n = 6), chronic postoperative bacterial endophthalmitis (n = 3), phacolytic glaucoma (n = 2), ghost cell glaucoma (n = 2), metastatic endophthalmitis (n = 1), post-traumatic lenticular abscess (n = 1), and iridocyclitis (n = 1). Treatment of the cases was successful. Conclusions:In selected cases, cytology of the aqueous humor reveals specific, with regard to the clinical entity, cell populations and other elements and thus contributes effectively to the differential diagnosis and therapeutic approach to some anterior uvea inflammations.

The role of C-reactive protein in the evaluation and management of infants with suspected sepsis.

C-reactive protein (CRP) is a nonspecific, acute-phase protein that rises in response to infectious and noninfectious inflammatory processes. Good evidence exists to support the use of CRP measurements in conjunction with other established diagnostic tests (such as a white blood cell (WBC) count with differential and blood culture) to establish or exclude the diagnosis of sepsis in full-term or near-term infants. This article reviews the immunologic function of CRP and the history of CRP testing. The 3 methods for measuring CRP and the sensitivity and specificity of this diagnostic test are analyzed. Guidelines for the use of CRP in the evaluation and management of infants with suspected sepsis are presented. Quantitative serial CRP levels, obtained 24 hours after the onset of signs and symptoms of infection, with serial measurements 12 to 24 hours apart, offer the most sensitive and reliable information. At least 2 CRP levels, obtained 24 hours apart, with levels < or = 10 mg/L, are needed to identify infants unlikely to be infected. The use of CRP to exclude infection may allow clinicians to discontinue antibiotics at 48 hours in select infants, limiting extended unnecessary antibiotic exposure.

Nerve Root Inflammation Demonstrated by Magnetic Resonance Imaging in a Patient with Transient Neurologic Symptoms after Intrathecal Injection of Lidocaine

Received from the Department of Anesthesiology and Critical Care Medicine, Hebrew University Hadassah Medical School, Hadassah University Hospital, Jerusalem, Israel.TRANSIENT neurologic symptoms after intrathecal injection of lidocaine are common. The main symptoms are severe pain and dysesthesia in the buttocks and legs after recovery from spinal anesthesia. The symptoms typically resolve within 1 week. No definitive etiology has been established until now. We report findings on magnetic resonance imaging (MRI) of a patient with transient neurologic symptoms after spinal anesthesia with lidocaine that indicated a local inflammatory process as the possible etiology for this symptom.A 60-yr-old healthy male patient (American Society of Anesthesiologists physical status class I) underwent excision of a perineal condylomata under spinal anesthesia. Anesthesia was performed with the patient in the sitting position with a 27-gauge pencil-point spinal needle (te me na SARL, Bondy, France) and 50 mg hyperbaric lidocaine (AstraZeneca, London, United Kingdom). Dural puncture was achieved in the first attempt, and no paresthesias were elicited. The hyperbaric lidocaine was diluted with cerebrospinal fluid. The patient remained seated for 5 min and then was placed in the prone jackknife position. Intraoperatively, the patient was hemodynamically stable, and the postoperative course was uneventful. The patient was released home pain-free within several hours following the procedure.The next morning, the patient began to feel pain in his lower back radiating to his buttocks and legs. During the next few hours, the pain became severe, and the patient returned to the hospital.On admission, the patient was in extreme discomfort and complained of intractable pain in his buttocks and thighs. There was no tenderness or signs of inflammation at the site of the spinal injection. Neurologic examination revealed no motor, sensory, or muscle–tendon reflex abnormalities. The patient denied having severe back pain or a similar episode in the past. Due to the severe pain and the radicular findings, we performed an MRI (with and without Gd-DTPA contrast material [Magnetol, Soreq, Israel]), which ruled out an epidural or spinal hematoma, direct nerve injury, or an infectious process. There were no signs of pressure to the cord or the spinal roots due to bulging discs or degenerative changes. The only abnormal finding was enhancement of the mildly thickened cauda equina and the lumbosacral nerve roots on the postcontrast study (post Gd-DTPA), which are consistent with nonspecific inflammatory or infiltrative processes (figs. 1 and 2).Due to the severe pain, the patient was treated with intravenous morphine (patient-controlled analgesia), and the pain decreased gradually within several hours. The patient was released the next day with mild pain, which fully resolved the following day.The use of intrathecal lidocaine came under scrutiny in the past decade after an increasing number of reports of severe neurologic symptoms (transient neurologic symptoms, cauda equina syndrome) after spinal anesthesia with lidocaine. 1There is a lower incidence of these symptoms when other local anesthetics are used for spinal anesthesia. 2–4This supports the hypothesis that lidocaine has a neurotoxic effect, although other mechanisms, such as local anesthetics maldistribution, myofascial pain, and surgical positioning, have been proposed. 5–9The mechanism of this postulated lidocaine toxicity is unknown. An ischemic effect of lidocaine on the spinal cord was ruled out. 10The result of the MRI in this case showing enhancement of the cauda equina and the lumbosacral nerve roots may support the theory of a direct toxic effect of lidocaine. The MRI findings are suggestive of pial hyperemia or breakdown of the nerve root–blood barrier by a noninfectious inflammatory process. A similar picture can be found in patients with Guillain-Barré and Krabbe (demyelinating disorder) syndromes. 11–13In Guillain-Barré syndrome, the degree of enhancement correlates well with the severity of the disease. 14The enhancement of the cauda equine roots indicates breakdown of the blood–nerve barrier. In the present case, it suggests a chemical irritation due to intrathecal anesthetic. This breakdown may be the cause of the neurologic deficit or just another effect of the intrathecal anesthetic. Until now, no studies were performed to investigate findings in MRI in patients after spinal anesthesia with and without neurologic symptoms. It is therefore impossible to conclude definitely from this case that the findings in the MRI prove direct toxic effect of lidocaine. However, in regard to similar MRI findings in other neurologic disorders, it is suggestive that toxic effects of lidocaine are the cause of the transient neurologic syndrome.

Portal vein thrombosis: spectrum of helical CT and CT angiographic findings.

Portal vein thrombosis (PVT) is the leading extrahepatic cause of portal hypertension in the Western world [1]. Etiologies of PVT include infectious processes such as sepsis, neoplasms that invade or compress the portal system such as hepatoma or pancreatic cancer, hypercoagulable states, myeloproliferative disorders, and noninfectious inflammatory processes [1, 2]. Patients are at risk for life-threatening variceal bleeds and refractory ascites. Visualization of abnormalities associated with portal vein thrombosis is crucial to diagnosis and appropriate intervention. The development of helical computed tomography (CT) has allowed volume acquisition of scanned tissues, with decreased susceptibility to motion artifacts and respiratory misregistration. Improvements in computer hardware and software have allowed real-time volume rendering of imaging data in three dimensions [3], which is especially helpful for imaging vascular pathology [4, 5]. This essay will review the spectrum of findings in portal vein thrombosis with an emphasis on the value of helical CT.

Adhesion molecules during immune response to exercise

Cell-cell and cell-matrix contacts are dependent on cell surface density, localization, and avidity state of adhesion molecules. These adhesion molecules are involved in all steps of the leukocyte's adhesion process. Selectins, molecules of the immunoglobulin superfamily, and integrins are necessary for an initial tethering, triggering, firm attachment, and transendothelial migration of leukocytes. Hormones, cytokines, other pro-inflammatory agents, and shedded receptors like the LPS-receptor significantly alter the adhesion process. Infectious and noninfectious inflammatory processes are capable of inducing an altered adhesion of leukocytes to endothelial cells. The result is a preferential homing of leukocytes to sites of inflammation. Acute bouts of exercise may induce a release or secretion of many of the aforementioned substances involved in the adhesion process. The acute immune response to exercise is strongly influenced by the activation of the sympathetic nervous system and the hypothalamo-pituitary-adrenal axis. During the first 10-30 min of exercise an almost maximal increase of T and B lymphocytes, monocytes, and NK cells from the marginal pool into the blood circulation is induced. This demargination of cells is likely an effect mediated by beta2 adrenergic receptors and probably due to a change of the avidity state of adhesion molecules. Strenuous exercise is associated with an increase of serum cortisol resulting in a delayed neutrocytosis and lymphocytopenia. Both phenomena are due to altered circulation patterns. It will be discussed how far adhesion molecules might contribute to this effect. Furthermore an evaluation of contradicting experimental results about surface expression of selectins and integrins will be provided.Key words: CD11a/CD18, CD11b/CD18, LFA-1, inflammation, infections, exercise, monocytes, neutrophils, lymphocytes.

The use of radiolabeled, nonspecific immunoglobulin in the detection of focal inflammation

The serendipitous discovery that radiolabeled nonspecific immunoglobulin G (IgG) accumulates at a site of focal inflammation has led to the development of a new radiopharmaceutical for inflammation scanning, 111In-IgG. This reagent has been extensively studied in humans with focal infection and has been shown to be both safe and effective. It has been especially useful in the evaluation of patients with possible abdominal and skeletal infection, with the ability to perform serial scans being an important attribute in terms of determining "proof of cure." Preliminary data suggest that this approach may be particularly useful in immuno-compromised patients and may find a role in the quantitative assessment of patients with such noninfectious inflammatory processes as rheumatoid arthritis and inflammatory bowel disease. A new method of labeling IgG with technetium, via the hydrazino nicotinamide derivative, holds promise in terms of substituting this more practical radionuclide for indium. However, caution must be directed against total substitution, because such processes as suspected vascular or skeletal prosthesis infection may require the longer half-life of 111In for satisfactory diagnosis. When one compares the results obtained with radiolabeled IgG against the ideal specifications for a radiopharmaceutical to be used for inflammation imaging, most of the requirements are met. The major weakness of this approach is that even with the technetium-labeled reagent, a minimum of 6 to 12 hours is necessary for a scan to become positive, which is not acceptable in the evaluation of acutely evolving processes. Development of other radiopharmaceuticals for this purpose remains to be accomplished.

Human immunodeficiency virus infection and the skin

The skin is commonly affected in the course of human immunodeficiency virus (HIV) infection. In many cases, skin findings may be the earliest sign of HIV disease or acquired immunodeficiency syndrome. When cutaneous diseases occur in unusual settings, such as zoster in a young individual, are increased in severity or fail to respond to routine therapy, the possibility of underlying immunodeficiency should be suspected. Skin diseases in HIV-infected hosts include primary infections, such as those caused by herpes simplex virus and molluscum contagiosum, as well as secondary involvement of systemic diseases, such as cryptococcosis and histoplasmosis. Noninfectious inflammatory processes, such as seborrheic dermatitis and psoriasis, as well as neoplasms, such as Kaposi's sarcoma and basal cell carcinoma, may all be seen in these patients. We review a number of these diseases and discuss their treatment. Clinicians must be aware of the cutaneous manifestations of HIV infection so that the disease will be recognized at an earlier point in time and therapy with zidovudine and prophylactic antibiotics will be instituted where appropriate.

Human Immunodeficiency Virus Infection and the Skin

The skin is commonly affected in the course of human immunodeficiency virus (HIV) infection. In many cases, skin findings may be the earliest sign of HIV disease or acquired immunodeficiency syndrome. When cutaneous diseases occur in unusual settings, such as zoster in a young individual, are increased in severity or fail to respond to routine therapy, the possibility of underlying immunodeficiency should be suspected. Skin diseases in HIV-infected hosts include primary infections, such as those caused by herpes simplex virus and molluscum contagiosum, as well as secondary involvement of systemic diseases, such as cryptococcosis and histoplasmosis. Noninfectious inflammatory processes, such as seborrheic dermatitis and psoriasis, as well as neoplasms, such as Kaposi's sarcoma and basal cell carcinoma, may all be seen in these patients. We review a number of these diseases and discuss their treatment. Clinicians must be aware of the cutaneous manifestations of HIV infection so that the disease will be recognized at an earlier point in time and therapy with zidovudine and prophylactic antibiotics will be instituted where appropriate. ( Arch Intern Med . 1991;151:1295-1303)

Spondylosis deformans in the female beagle dog: A radiographic study

ABSTRACTSpondylosis deformans is a generalised disease of ageing resulting in formation of bony osteophytes around degenerating intervertebral discs throughout the vertebral column. It is noninflammatory and needs to be differentiated from spondylitis, which is either an infectious or noninfectious inflammatory process. Lateral radiographs of 310 female beagle dogs from a closed colony showed development of spondylosis deformans that was age‐dependent and located principally at discs numbers 5, 15, and 20 to 23. It was noteworthy that disc 26 was minimally involved whereas this location has been previously reported to have frequent involvement in larger breeds of dogs. None of the dogs studied had clinical signs causing their removal from the colony, further supporting the concept that spondylosis deformans as a bony response to disc degeneration is not a cause of severe pain or lameness.