ABSTRACT
The authors describe four cases of obturator internus muscle (OIM) abscess in children, including their clinical presentations and treatment. This was a retrospective chart review. Children and adolescents younger than 18 years discharged between July 1, 1985, and September 30, 1998, from Brenner Children's Hospital with the diagnosis of muscle abscess or pelvic abscess were identified. A total of 56 patients were identified with the diagnosis of muscle abscess or pelvic abscess. OIM abscess was defined by radiologic findings of an inflammatory process with fluid collection in the OIM, along with the clinical findings suggestive of an OIM abscess. Four of the patients met the definition of OIM muscle abscess. The common presenting features were fever, limp, and hip pain. Computed tomography or magnetic resonance imaging was diagnostic in all four patients, and Staphylococcus aureus was the causative agent in each. All the patients recovered, one after surgical drainage and the other three after antimicrobial therapy alone or with needle aspiration. The presentation of OIM pyomyositis is similar to that of psoas muscle pyomyositis and other infectious processes of the pelvis and hip. The S. aureus is the most common etiologic agent but not the only one reported. Most patients can be managed without open surgical drainage, but needle aspirations may be helpful both therapeutically and diagnostically.
Subject(s)
Abscess/diagnosis , Myositis/diagnosis , Abscess/therapy , Child , Diagnosis, Differential , Female , Humans , Male , Myositis/therapy , Retrospective StudiesABSTRACT
Tyrosine phosphorylation pathways are essential components of the process of macrophage activation and the resultant production of inflammatory mediators such as tumor necrosis factor (TNF) and nitric oxide (NO). Several lines of evidence suggest that members of the src family of protein tyrosine kinases play important roles in macrophage activation by gram-negative bacterial lipopolysaccharide (LPS) or the cytokine interferon-gamma (IFN-gamma), but targeted disruption of three members of the src family (hck, fgr, and lyn) in mice failed to demonstrate a requirement for these particular kinases in macrophage activation. We report that the pyrazolopyrimidine PP1, a src family-selective tyrosine kinase inhibitor, potently inhibits the production of TNF and inducible nitric oxide synthase (iNOS) in RAW 264.7 murine macrophages stimulated with LPS, rlFN-gamma, or LPS + rIFN-gamma. Furthermore, the tested concentrations of PP1 inhibit LPS- and rlFN-gamma-mediated tyrosine phosphorylation of the hck tyrosine kinase and its putative substrate, vav, but fail to block rlFN-gamma-mediated JAK2 tyrosine phosphorylation. These findings provide additional support for a model of macrophage activation involving one or more src-related kinases. Selective inhibitors of this signaling pathway should be studied in animal models of sepsis.
Subject(s)
Cell Cycle Proteins , Interferon-gamma/metabolism , Macrophages/drug effects , Nitric Oxide Synthase/metabolism , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , src-Family Kinases/antagonists & inhibitors , Animals , Cell Line/drug effects , Cell Line/metabolism , Enzyme Inhibitors/pharmacology , Janus Kinase 2 , Lipopolysaccharides/antagonists & inhibitors , Macrophages/metabolism , Mice , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase Type II , Phosphorylation , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/drug effects , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/drug effects , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-hck , Proto-Oncogene Proteins c-vav , Tumor Necrosis Factor-alpha/drug effects , Tyrosine/metabolismSubject(s)
Bronchodilator Agents/administration & dosage , Croup/drug therapy , Epinephrine/administration & dosage , Steroids/therapeutic use , Acute Disease , Administration, Inhalation , Bronchitis/drug therapy , Bronchitis/virology , Child, Preschool , Croup/virology , Female , Humans , Infant , Male , Tracheitis/drug therapy , Tracheitis/virology , Treatment OutcomeABSTRACT
Viridans streptococci are an important cause of bacteremia and septic shock in neutropenic patients, especially patients receiving chemotherapeutic agents that induce severe mucositis. The mechanisms by which viridans streptococci cause septic shock are unclear. We hypothesized that septic shock due to viridans streptococci is attributable to host cytokine production. Three clinical isolates of viridans streptococci were evaluated for their ability to induce production of tumor necrosis factor-alpha (TNF-alpha) by RAW 264.7 murine macrophages. These three strains of viridans streptococci induced TNF-alpha in a dose-dependent fashion, and the kinetics of TNF-alpha induction were similar to those observed with a clinical isolate of Escherichia coli.
Subject(s)
Macrophages/immunology , Shock, Septic/microbiology , Streptococcal Infections/microbiology , Streptococcus/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Cell Line , Escherichia coli/immunology , Humans , Interferon-gamma/pharmacology , Kinetics , Mice , RNA, Messenger/genetics , RNA, Messenger/metabolism , Shock, Septic/immunology , Streptococcal Infections/immunology , Streptococcus/isolation & purificationABSTRACT
We and others have previously reported that tyrosine kinases play key roles in the activation of macrophages by both bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). However, little is known regarding the substrates of tyrosine phosphorylation that mediate macrophage activation and the resultant production of inflammatory mediators. In lymphocytes and other hematopoietic lineages, tyrosine phosphorylation of the proto-oncogene vav appears to be an essential component of cell activation. In this study, we demonstrate that both LPS and rIFN-gamma trigger the prompt, dose-dependent tyrosine phosphorylation of vav in murine RAW 264.7 macrophages. In addition, vav is physically associated with the src-related kinase hck in murine macrophages, and antisense oligonucleotides specific for murine hck block both LPS and rIFN-gamma-mediated vav phosphorylation. These findings suggest that hck probably mediates vav tyrosine phosphorylation during macrophage activation and that LPS and rIFN-gamma-mediated signaling pathways partially overlap.
Subject(s)
Cell Cycle Proteins , Interferon-gamma/pharmacology , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/metabolism , Signal Transduction/drug effects , Animals , Cell Line , Macrophage Activation/drug effects , Mice , Phosphorylation , Proto-Oncogene Proteins c-hck , Proto-Oncogene Proteins c-vav , Recombinant Proteins , Tyrosine/metabolismABSTRACT
During a 30-month interval at LeBonheur Children's Medical Center, 394 patients had a blood or cerebrospinal fluid culture positive for Streptococcus pneumoniae. Sixteen of these episodes (4%) were repeated infections; 6 of these 16 patients had sickle cell disease. Six of the remaining 10 patients had immunologic evaluations of varying completeness; no immunodeficiency was identified by these tests or on follow-up. Nine of the ten previously healthy patients with repeated pneumococcal disease were less than 2 years of age. In our experience, repeated invasive pneumococcal infections in otherwise healthy young children were relatively common (10/394, or 2.5% of patients with invasive pneumococcal infections) and did not indicate the presence of an unsuspected immunodeficiency.
Subject(s)
Immunologic Deficiency Syndromes , Pneumococcal Infections/diagnosis , Bacteremia/diagnosis , Bacteremia/microbiology , Child, Preschool , Female , Humans , Infant , Male , Penicillin Resistance , Pneumococcal Infections/microbiology , Recurrence , Retrospective Studies , Serotyping , Streptococcus pneumoniae/classification , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/isolation & purification , Time FactorsABSTRACT
Bacterial endotoxin or lipopolysaccharide is the major proinflammatory component of gram-negative bacteria, but the components of gram-positive bacteria that trigger the inflammatory cascade are poorly understood. Lipoteichoic acid (LTA) purified from 2 strains of viridans streptococci induced the accumulation of tumor necrosis factor (TNF) mRNA and protein by the murine macrophage cell line RAW 264.7 in a dose- and time-dependent manner. Furthermore, in the presence of recombinant interferon-gamma, LTA from both strains of viridans streptococci provoked the accumulation of inducible nitric oxide (NO) synthase mRNA and the production of NO. Together these observations indicate that LTA can trigger macrophage activation and the production of TNF and NO and suggest that LTA may be an important determinant of the host inflammatory response to gram-positive infection.
Subject(s)
Lipopolysaccharides/pharmacology , Macrophages/metabolism , Macrophages/microbiology , Nitric Oxide/biosynthesis , RNA, Messenger/biosynthesis , Streptococcus mutans/chemistry , Streptococcus sanguis/chemistry , Teichoic Acids/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Blotting, Northern , Cells, Cultured , Dose-Response Relationship, Drug , Interferon-gamma/pharmacology , Lipopolysaccharides/isolation & purification , Macrophage Activation , Mice , Nitric Oxide Synthase/biosynthesis , Nitric Oxide Synthase/genetics , RNA, Messenger/isolation & purification , Recombinant Proteins , Teichoic Acids/isolation & purification , Time Factors , Tumor Necrosis Factor-alpha/geneticsABSTRACT
The temporal requirements for tyrosine phosphorylation in the induction of tumor necrosis factor (TNF) and inducible nitric oxide synthase (NOS) were compared in the routine macrophage cell line RAW 264.7. Preincubation of RAW 264.7 cells with herbimycin A or genistein (but not with either of three tyrphostins tested) significantly blocked TNF and NOS production on exposure of these cells to combinations of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). The addition of either genistein or herbimycin A to RAW 264.7 cell cultures 1-6 It after stimulation with LPS and IFN-gamma had little or no effect on TNF production but markedly inhibited NOS protein accumulation. Together these data indicate that tyrosine kinase inhibitors block NOS production at a point well downstream of the initial wave of LPS- and IFN-gamma-mediated protein tyrosine phosphorylation.
Subject(s)
Isoflavones/pharmacology , Macrophages/metabolism , Nitric Oxide Synthase/biosynthesis , Protein-Tyrosine Kinases/antagonists & inhibitors , Quinones/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis , Tyrphostins , Animals , Benzoquinones , Benzylidene Compounds , Cells, Cultured , Enzyme Inhibitors/pharmacology , Genistein , Interferon-gamma/pharmacology , Lactams, Macrocyclic , Lipopolysaccharides/pharmacology , Macrophage Activation , Macrophages/drug effects , Macrophages/enzymology , Mice , Nitriles , Rifabutin/analogs & derivativesSubject(s)
Arthritis, Infectious/microbiology , Osteomyelitis/microbiology , Pneumococcal Infections , Arthritis, Infectious/diagnosis , Cephalosporin Resistance , Child, Preschool , Female , Hospitals, Pediatric , Humans , Infant , Male , Osteomyelitis/diagnosis , Penicillin Resistance , Pneumococcal Infections/drug therapyABSTRACT
The anti-cryptosporidial immunoglobulin G antibodies in two commercially available human serum immunoglobulin (HSIG) products were quantified and characterized. The mean level of Cryptosporidium parvum-specific immunoglobulin G in HSIG was eightfold higher than the antibody level found in the sera of three immunocompetent individuals convalescing from cryptosporidiosis. However, HSIG products displayed no reactivity to cryptosporidial antigens in immunoblot analyses, while convalescent-phase sera demonstrated characteristic banding patterns. When HSIG was given to newborn severe combined immunodeficiency (scid) mice before and shortly after experimental infection, a decreased intensity of infection was observed in the intestines of the mice compared with that of control mice. However, there was no difference in mortality or histopathologic findings in the intestines of HSIG-treated and control mice when treatment was not started until 22 days of age. These results indicate that HSIG may be beneficial when given prophylactically; however, HSIG cannot eradicate cryptosporidia from mucosal surfaces in an established infection.
Subject(s)
Cryptosporidiosis/therapy , Immunoglobulin G/therapeutic use , Adult , Animals , Animals, Newborn , Antibodies, Monoclonal/therapeutic use , Antibodies, Protozoan/analysis , Enzyme-Linked Immunosorbent Assay , Humans , Intestines/immunology , Mice , Mice, SCIDABSTRACT
Helicobacter cinaedi has been most frequently isolated from rectal swabs of homosexual men with proctocolitis. The microorganism is a normal intestinal inhabitant of hamsters. We report a case of septicemia and meningitis by H. cinaedi in a neonate whose mother cared for pet hamsters during the first two trimesters of her pregnancy. The isolate was detected after 3 days of incubation in a Bact/Alert pediatric blood culture vial and an enrichment broth culture of the cerebrospinal fluid. H. cinaedi should be added to the list of unusual fastidious organisms that cause sepsis and meningitis in the newborn.
Subject(s)
Helicobacter Infections , Meningitis/microbiology , Sepsis/microbiology , Animals , Animals, Domestic/microbiology , Cricetinae/microbiology , Fatty Acids/analysis , Female , Helicobacter/isolation & purification , Helicobacter Infections/transmission , Humans , Infant, Newborn , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, SecondABSTRACT
Three young children with Down syndrome developed fever, cough, wheezing, irritability, and tachypnea. They had bilateral infiltrates on their chest radiographs and developed respiratory distress, which required their hospitalization. Laboratory studies suggested that the children had mycoplasma pneumonia. These children may have experienced severe mycoplasma infections early in life because of their Down syndrome-associated immune abnormalities. When young children with Down syndrome develop pneumonia, physicians should consider Mycoplasma pneumoniae as the possible etiologic agent.