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Background: Hyper-IgE syndrome (HIES) is characterized by recurrent pyogenic infections, eczema, increased serum IgE levels, and a variety of connective tissue and skeletal system abnormalities. Little has been published regarding the causes of death in these patients or pathologic findings., Objective: To identify the cause of death in patients with HIES and to describe pathologic findings in fatal HIES., Methods: We reviewed the medical records and autopsy slides of 6 patients with HIES with autopsies performed at our institution., Results: All 6 patients with HIES were women and ranged in age from 24 to 40 years. All patients had a history of cystic lung disease and had pneumonia at the time of death, with Pseudomonas aeruginosa and fungal organisms predominating. Pulmonary fungal vascular invasion with fatal hemorrhage was observed in 3 patients, and metastatic fungal disease to the brain was observed in 2 patients caused by Aspergillus fumigatus and Scedosporium prolificans. Four patients had evidence of renal tubular injury, which was likely from amphotericin B toxicity; 3 patients had glomerulosclerosis; and 1 patient had 2 kidney angiomyolipomas., Conclusions: Our series highlights the important role Pseudomonas and Aspergillus species play in patients with HIES with cystic lung disease. Intensified antifungal and gram-negative bacterial prophylaxis need evaluation as possible strategies to prevent these infectious complications in patients with cystic lung disease., Clinical Implications: Fungal and Pseudomonas infection of cystic lung disease in HIES may be life threatening, and the proper management and prevention of these infections need continued investigation.

Hyper IgE recurrent infection syndrome (HIES, or Job's syndrome) is a primary immunodeficiency characterized by recurrent skin and lung infections, eczema, elevated serum immunoglobulin E (IgE) levels, and various connective tissue and skeletal system abnormalities including characteristic facies, scoliosis, joint hyperextensibility, retained primary dentition, craniosynostosis, osteopenia, and pathologic fractures. We have identified two patients with aneurysmal coronary artery disease. One was a forty-three-year-old man with HIES and coronary artery aneurysms and ectasia identified on cardiac catheterization following myocardial infarction. The other was a 48-year-old man with coronary artery ectasia-aneurysm identified after cardiac catheterization for evaluation of chest pain. Although connective tissue abnormalities are common in HIES, this is the first report of coronary artery aneurysms in HIES. Further studies are necessary to determine the incidence, pathogenesis, and optimal therapy of these arterial abnormalities in HIES.

Mycobacteria, Salmonella and Helicobacter species have all evolved mechanisms to evade host defenses and cause persistent infection in humans. Host control of mycobacteria and Salmonella is largely achieved by the IFN-gamma/IL-12 pathway. Immune disorders affecting this pathway are characterized by disseminated infections with environmental or nontuberculous mycobacteria. Helicobacter is a predominantly extracellular bacterium that uses its remarkable genetic diversity (as well as other mechanisms) in order to evade host defenses. The importance of humoral immunity in containing Helicobacter infections to the mucosal surface is illustrated by the primary immune disorder, X-linked agammaglobulinemia in which patients are prone to chronic bacteremia and skin infections by Helicobacter and related species such as Flexispira and Campylobacter. Exploration of these particular infections in their specific immune defects sheds light on both host and bacterial mechanisms that have implications for pathogenesis and therapy.

We report 2 sisters with hyper-IgE syndrome treated with daily suppressive dosages of linezolid (LZD) who developed LZD-resistant Staphylococcus aureus carrying the G2576T mutation in the 23S rRNA gene. Molecular typing suggested transmission of the resistant strain from one sister to the other. LZD-susceptible S. aureus was isolated 2 months after LZD discontinuation. LZD-resistant S. aureus remains rare but may occur while receiving suppressive therapy.

Hyper IgE syndrome, or Job's syndrome, is an immunodeficiency syndrome characterized by eczema, recurrent infections and elevated serum immunoglobulin E levels. Individuals tend to have frequent staphylococcal abscesses and pneumonias early in life, often developing pneumatocoeles that predispose them to later fungal and Gram-negative bacterial infections. In addition to the immunologic abnormalities, hyper IgE syndrome is now recognized as a multisystem disorder with skeletal and morphologic features such as characteristic facies, osteopenia, scoliosis, fractures and retention of the primary teeth. Therapy of hyper IgE syndrome involves careful skin care, antimicrobial prophylaxis and aggressive treatment of infections, as well as treatment of some of the complicating abnormalities, such as scoliosis. The genetic etiology of hyper IgE syndrome remains unknown, however, it continues to be investigated. Identification of the genetic etiology or etiologies of this syndrome will allow for targeted therapies as well as great advances in understanding the connections between immunologic function and connective tissue.

Chronic granulomatous disease (CGD), a rare immunodeficiency, typically presents with recurrent infections caused by catalase-positive organisms. We report 2 patients with CGD who presented with eosinophilic inflammatory conditions recognized before the diagnosis of CGD. Both patients had significant urologic disease. Physicians should be aware of the association of CGD with eosinophilic inflammatory conditions.

Angiogenesis has been shown to be dysregulated in coronary artery (CA) aneurysms in the chronic phase of Kawasaki disease (KD). Neovascularization may occur in inflammatory-related vascular diseases because many angiogenesis mediators are secreted by inflammatory cells. We hypothesized that inflammation of the acute KD CA aneurysm could lead to dysregulation of angiogenesis mediators and subsequent neovascularization. To investigate this hypothesis, acute fatal KD cardiac tissues were immunostained for angiogenic inducers and inhibitors. Microvessel density was determined and the degree of inflammation assessed. Marked inflammation and angiogenesis were found in acute KD CA aneurysms and myocardium, with the highest microvessel density seen in patients who died 2-3 weeks after onset of the disease. Expression of proangiogenic proteins was higher than expression of inhibitors in KD CA aneurysms and myocardium. Angiogenesis mediators were localized to inflammatory cells in the myointima, adventitia, and myocardium. We conclude that significant neovascularization occurs in acute KD CA aneurysms and myocardium much sooner after onset of the disease than has been previously reported, that multiple angiogenesis factors are involved, and that dysregulation of angiogenesis likely contributes to KD vasculopathy.

Abiotrophia and Granulicatella species have been associated with various infections. Antimicrobial susceptibility data for these nutritionally variant streptococcus-like organisms, especially for pediatric isolates, are very limited. Little is known about the genetic bases of their resistance mechanisms. We report the results of identification to bacterial species level, antimicrobial susceptibility testing, macrolide resistance testing, and detection of genes encoding that resistance for a collection of 15 pediatric clinical isolates from normally sterile sites. Our results indicate that the prevalence of beta-lactam and macrolide resistance is high and that both erm and mef are found in these isolates.

Recent reports from the Institute of Medicine and other sources have shown that far too many avoidable medical errors occur; other research has shown a strong association between patient outcomes and characteristics of nursing staff. The authors of this paper present findings from multimethod research conducted over three years in 29 small rural hospitals in nine Western states. They examined the organizational processes used to recognize medical errors and assign responsibility for them to resolve patient-safety issues. The research comprises seven substudies that used surveys, questionnaires, interviews, and case studies to gather data from nurses, physicians, administrators, pharmacists, and other health care workers.Generally, participants responded positively to questions about an institution's receptivity to communicating about errors and agreed on the most common kinds of errors that occur. But other data suggest that providers' understanding of patient safety is heavily conditioned by preconceived notions of what constitutes an error and of professional roles. Participants' analyses of case studies showed that they don't agree on what constitutes error or what kinds of events should be reported. And in one substudy, even when there was overwhelming agreement among participants (97%) that an error had occurred, only 64% would disclose the error to the patient affected. Physicians, administrators, and nurses tended to perceive patient safety as primarily a nursing responsibility. Only 22% of respondents to one survey said that physicians, nurses, pharmacists, and administrators should share responsibility equally for patient safety. The research was not designed to answer specific questions about the recruitment and retention of nurses, but the data collected suggest that institutional processes used to identify errors, assign responsibility for them, and resolve patient-safety issues may have unintended, harmful effects on nurse recruitment and retention. The authors propose that "a systems approach to patient safety" be adopted, one in which responsibility for safety is shared by all members of the health care team.

Pasteurella multocida has been reported to cause peritoneal dialysis-associated peritonitis after a cat bite or scratch to the catheter. We report a teenager with hamster bite peritonitis caused by P. aerogenes, an organism predominantly isolated from swine.

Empyema necessitatis is a rare complication of empyema characterized by extension of suppuration from the pleural space through the chest wall. The most common etiologies are tuberculosis and actinomycosis. We describe a 1-year-old boy with Streptococcus pneumoniae empyema necessitatis and review previously reported cases.

Purpose: To describe the context of, and beliefs about, smoking cessation in a sample of low-income African American pregnant women., Study Design & Methods: A naturalistic descriptive qualitative approach was used with 15 women. Face-to-face interviews were conducted using a semi-structured interview guide. Interviews were transcribed verbatim and a thematic content analysis conducted. Perinatal health complication data were extracted from the participants' medical records and summarized., Results: Two major themes were identified. The context of smoking cessation theme was Living the Stressful Life, with subthemes of Personal and Community Stress, Personal Health Problems, and Smoking For Stress Management. The second major theme was Personal Accountability for Smoking Cessation. There was a mismatch between women's sources of stress (which were out of their control) and their perceived locus of change (which was personal behavior)., Clinical Implications: To improve the outcomes of tobacco control programs for low-income women, we need to take action to create healthier communities.

Symptomatic pulmonary manifestations of Kawasaki disease (KD) are uncommon. However, epidemiologic, radiologic, and histologic studies have indicated that respiratory symptoms and findings occur in KD and suggest that the KD agent may have a respiratory portal of entry. We report on three young infants with KD who developed pulmonary nodules, in addition to coronary artery aneurysms. Two patients had pathologic specimens available, one from biopsy and the other from autopsy. The nodules had predominantly mononuclear cell infiltrates, which were within the lung parenchyma and infiltrating vessel walls. Immunohistochemical studies of the nodules, using antibodies to common leukocyte antigen (LCA) and factor VIII-related antigen, confirmed the inflammatory nature of the lesions and showed capillary proliferation. IgA plasma-cell infiltration was observed in the nodule, consistent with previous KD findings of IgA plasma-cell infiltration in the vessel walls, kidneys, pancreas, and upper respiratory tract. The two patients with nonfatal KD were treated with intravenous immunoglobulin and aspirin, with resolution of the nodules. We propose that when pulmonary involvement occurs in KD, it ranges from subclinical interstitial micronodular infiltrates to larger inflammatory pulmonary nodules. These pulmonary infiltrates and nodules likely reflect the host response to the etiologic agent of KD, and may resolve with the disease process. Recognition of this pulmonary complication of KD may enable cautious observation of such lesions for spontaneous resolution., (Copyright 2003 Wiley-Liss, Inc.)

Noma neonatorum was suggested as a distinct entity characterized by a gangrenous process of the nose, oral cavity, eyelids and perineum that was almost universally fatal in premature infants with Pseudomonas sepsis. We report the first case of noma neonatorum in a 26-week-gestation twin born in the United States. Our case is consistent with previous descriptions of noma neonatorum; however, we question the distinction between noma neonatorum and a neonatal presentation of ecthyma gangrenosum.

Kawasaki disease is now being recognized as the leading cause of acquired heart disease in children in North America and Japan. This review discusses the recent developments and controversies in Kawasaki disease. Increasing evidence has supported an infectious etiology for Kawasaki disease; however, the debate continues as to whether the inflammatory response results from a conventional antigen or a superantigen. Recent immunohistochemistry findings suggest many vascular growth factors then play a role in the formation of the coronary artery lesions. Many studies have focused on the identification and therapy for patients resistant to conventional therapy, as well as the long-term prognosis of Kawasaki disease survivors. The recent advances in Kawasaki disease are helping to provide some clues in the etiology, pathogenesis and therapy for Kawasaki disease.