Helicobacter pylori Chronic-Stage Inflammation Undergoes Fluctuations That Are Altered in tlpA Mutants.

Helicobacter pylori colonizes half of the world's population and is responsible for a significant disease burden by causing gastritis, peptic ulcers, and gastric cancer. The development of host inflammation drives these diseases, but there are still open questions in the field about how H. pylori controls this process. We characterized H. pylori inflammation using an 8-month mouse infection time course and comparison of the wild type (WT) and a previously identified mutant lacking the TlpA chemoreceptor that causes elevated inflammation. Our work shows that H. pylori chronic-stage corpus inflammation undergoes surprising fluctuations, with changes in Th17 and eosinophil numbers. The H. pylori tlpA mutant changed the inflammation temporal characteristics, resulting in different inflammation from the wild type at some time points. tlpA mutants have equivalent total and gland colonization in late-stage infections. During early infection, in contrast, they show elevated gland and total colonization compared to those by WT. Our results suggest the chronic inflammation setting is dynamic and may be influenced by colonization properties of early infection.

The degree of Helicobacter pylori-triggered inflammation is manipulated by preinfection host microbiota.

Helicobacter pylori infects over 3 billion people worldwide and is the primary risk factor for gastric cancer. Most individuals infected with H. pylori develop only asymptomatic gastritis; however, some develop ulcers or gastric adenocarcinoma. We demonstrate that one previously unappreciated parameter influencing H. pylori disease outcome is variation in the preinfection host microbiota. Utilizing a mouse model, we altered the microbiota by antibiotic treatment and found that these alterations resulted in significantly lowered H. pylori-triggered inflammation. Specifically, antibiotic pretreatment reduced CD4(+) T-helper cells and Ifnγ transcript levels in gastric tissue after H. pylori infection. The bacterial communities in mice with a reduced response to H. pylori displayed many differences from those in untreated mice, including significantly more cluster IV and XIVa Clostridium spp., bacteria known to influence inflammation via regulatory T cell populations. Our findings suggest that microbiota composition, perhaps Clostridium spp., contributes to the variable disease outcome of H. pylori infection by altering the recruitment of CD4(+) T cells to the gastric compartment. Our results suggest that gastric microbiota could be used as a diagnostic tool to determine which patients are at risk for developing severe disease.

Helicobacter pylori requires TlpD-driven chemotaxis to proliferate in the antrum.

Different disease outcomes of Helicobacter pylori infection correlate with distinct inflammation patterns. These different inflammatory distributions may be initiated by differences in bacterial localization. One H. pylori property known to affect murine stomach localization is chemotaxis, the ability to move in response to chemical cues. In this report, we used nonchemotactic mutants (Che(-)) to analyze whether chemotaxis is required for initial colonization of particular stomach regions or for subsequent growth therein. We found that H. pylori behaves differently in the corpus, antrum, and corpus-antrum transition zone subregions of the stomach. This outcome suggests that these regions contain unique chemotactic signals. In the corpus, H. pylori utilizes chemotaxis for initial localization but not for subsequent growth. In contrast, in the antrum and the corpus-antrum transition zone, chemotaxis does not help initial colonization but does promote subsequent proliferation. To determine which chemoreceptor is responsible for the corpus-antrum phenotypes, we infected mice with strains lacking each chemoreceptor. Strains lacking TlpA, TlpB, or TlpC displayed only modest deviations from the wild-type phenotype, while strains lacking TlpD resembled the Che(-) mutant in their antral colonization defect and fared even worse than the Che(-) mutant in the corpus. Additional analysis showed that inflammation is worse in the antrum than in the corpus in both wild-type and Che(-) mutant infections. These results suggest that chemotaxis, specifically, that controlled by TlpD, is necessary for H. pylori to survive or grow in the environment of increased inflammation in the antrum.

Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection.

The host inflammatory response to chronic bacterial infections often dictates the disease outcome. In the case of the gastric pathogen Helicobacter pylori, host inflammatory responses result in outcomes that range from moderate and asymptomatic to more severe with concomitant ulcer or cancers. It was found recently that H. pylori chemotaxis mutants (Che(-)), which lack directed motility but colonize to nearly wild-type levels, trigger less host inflammation. We used these mutants to observe host immune responses that resulted in reduced disease states. Here we report that these mutants are defective for early gastric recruitment of CD4(+) T cells compared with wild-type infection. Furthermore, Che(-) mutant infections lack the T-helper cell, type 17 (Th17) component of the immune response, as measured by cytokine mRNA levels in gastric tissue via intracellular cytokine staining and immunofluorescence. We additionally find that a Che(-) mutant infection results in significantly less host cell apoptosis than does wild-type infection, in accordance with previous observations that T-helper cell, type 17 responses in Citrobacter rodentium infections are driven by concomitant bacterial and apoptotic cell signals. We propose that bacterial chemotaxis allows H. pylori to access a particular host niche that allows the bacteria to express or deliver proapoptotic host cell factors. This report indicates that chemotaxis plays a role in enhancing apoptosis, suggesting bacterial chemotaxis systems might serve as therapeutic targets for infections whose symptoms arise from host cell apoptosis and tissue damage.

Association of cervical cytology and HPV DNA status during pregnancy with placental abnormalities and preterm birth.

The clinical implications of abnormal cervical cytology during pregnancy are unclear. Therefore, we performed the present study to determine the role of cervical cytologic screening during pregnancy in association with placental abnormalities and preterm birth. A review of 2,480 cases during 11 years revealed significant correlation of reactive, infectious, atypical, and dysplastic cytologic changes during pregnancy with abnormal placental findings. Also, all but dysplastic cytologic changes were significantly associated with preterm birth. Furthermore, we observed significant association of the presence of high-risk human papillomavirus (HPV) DNA with preterm birth and placental abnormalities. These findings indicate that cervical infection of HPV is a risk factor for preterm birth and that cervical cytology is an effective tool for screening women for infection and inflammation during pregnancy and predicting pregnancy outcome.

Gastrointestinal stromal tumors: a review of the literature.

Gastrointestinal stromal tumors are mesenchymal neoplasms with a spectrum of histologic appearances and biologic activity. The morphologic classification of these lesions has evolved over time, and molecular analysis has led to a better understanding of their nature. The histologic differential diagnosis for these lesions is broad and includes many spindle cell lesions of the gastrointestinal tract, including neoplasms of true smooth muscle and neural origin, proliferating fibrous lesions, metastatic neoplasms, and primary sarcomas of vascular and adipose origin. Immunohistochemical studies that include CD117 have become invaluable in the classification of mesenchymal lesions arising in the gastrointestinal tract. Treatment of gastrointestinal stromal tumors has historically been involved surgery, but the use of the chemotherapeutic agent imatinib mesylate for advanced disease has made accurate classification even more important. The molecular features have not only allowed us to understand the pathogenesis of these tumors but also have proven to be associated with response to kinase inhibitors.

Nonkeratinizing undifferentiated nasopharyngeal carcinoma: a case report.

BACKGROUND: Nasopharyngeal carcinoma, a malignant neoplasm of squamous origin, is an uncommon neoplasm in the United States, although it is a significant cause of morbidity and mortality in southeast Asia and northern Africa. These lesions arise most frequently from the lateral wall of the nasopharynx and may be locally aggressive or metastasize regionally or distantly. CASE: A 46-year-old African American male presented to our institution with a 5-month history of nasal congestion. Imaging studies revealed a mass filling the right sphenoid sinus and eroding into the adjacent sinuses and temporal bone. A biopsy was performed, and immediate imprint cytology showed two populations of cells, lymphoid cells and cohesive clusters of cells with prominent nucleoli. A diagnosis favoring nasopharyngeal carcinoma was rendered, and subsequent histology showed a nonkeratinizing undifferentiated nasopharyngeal carcinoma. CONCLUSION: Nasopharyngeal carcinoma, particularly in its nonkeratinizing undifferentiated form, may mimic inflammatory and lymphoproliferative disorders. Careful examination for the distinct cytologic features is necessary for accurate diagnosis and subsequent treatment.

Extraintestinal manifestations of Edwardsiella tarda infection: a 10-year retrospective review.

Edwardsiella tarda, a member of the family Enterobacteriaceae found in aquatic environments, is an unusual cause of human disease, presenting most frequently as gastroenteritis. Extraintestinal manifestations of E. tarda infection are rare but have included meningitis, cholecystitis, endocarditis, osteomyelitis, soft tissue infections, bacteremia, and septicemia. Over a 10-year period at our institution, 10 cases of extraintestinal infection related to E. tarda were identified. The infections ranged from soft tissue infections secondary to trauma to intra-abdominal infections with abscess formation. Several of the patients had documented factors predisposing them to infection including diabetes mellitus and C1 esterase deficiency. Interestingly, two of the patients had chronic idiopathic inflammatory bowel disease, and one patient developed a respiratory tract infection related to E. tarda, a previously unreported clinical manifestion. Although the mortality rate for extraintestinal E. tarda infections has been as high as 50% in some studies, antimicrobial treatment was eventually successful in each of the 10 cases at our institution.

Antemortem diagnosis of asbestosis by screening chest radiograph correlated with postmortem histologic features of asbestosis: a study of 273 cases.

BACKGROUND: Accuracy in the clinical diagnosis of asbestosis has significant implications for the future health of affected patients as well as serious medicolegal implications for both patients and asbestos-associated industries. The radiographic gold-standard for diagnosis of asbestosis has been the plain chest radiograph, and in many asbestosis-screening clinics, chest radiograph abnormalities in conjunction with a history of asbestos exposure have been the mainstay of diagnosis. No studies have yet compared the antemortem chest radiographic diagnosis of asbestosis with the subsequent presence of pulmonary fibrosis and lung tissue ferruginous bodies at autopsy. METHODS: Records were reviewed from 273 autopsies performed to investigate asbestosis over an 11-year period. Accrued data included age and gender as well as the presence or absence of the following: occupational exposure to asbestos, antemortem clinical diagnosis of asbestosis by chest radiograph, fibrous pleural plaques, peribronchiolar or interstitial pulmonary fibrosis, ferruginous bodies in histologic sections of lung tissue, and ferruginous bodies in digested lung tissue. RESULTS: 242 cases with the antemortem radiographic diagnosis of asbestosis (study group) were identified. 31 additional autopsies had been requested based on history of asbestos exposure without radiographic documentation of asbestosis (control group). Comparison of the two groups showed a statistically significant increase in the association of chest radiograph-diagnosed asbestosis and the presence at autopsy of pleural plaques (p = 0.0109), peribronchiolar or interstitial pulmonary fibrosis (p = 0.0472), and histologically-diagnostic asbestosis (p = 0.0021). At autopsy, histologically-diagnostic asbestosis was confirmed in only 90 of the 243 study group cases. Comparison of individual parameters within the 242 study group cases showed a statistically significant correlation between the presence of fibrous pleural plaques and histologically-proven pulmonary fibrosis (p = 0.0025) as well as the subsequent histologic diagnosis of asbestosis (p < 0.0001). CONCLUSION: Clinical diagnosis of asbestosis by screening chest radiograph is more predictive of the postmortem presence of fibrous pleural plaques, pulmonary fibrosis, and histologically-proven asbestosis than is occupational exposure history alone. However, chest radiograph-based diagnosis of asbestosis significantly overpredicts the subsequent histologic diagnosis of asbestosis.

Tricuspid valve and pacemaker endocarditis due to Pseudallescheria boydii (Scedosporium apiospermum).

We report a case of native valve and pacemaker endocarditis in a 78-year-old male with diabetes mellitus who died after cardiac surgery. At autopsy, tricuspid valve vegetations and lung abscesses containing thick, hyaline, septate, and branching hyphae were present. The culture identified Scedosporium apiospermum, an infrequent cause of opportunistic infections in immunocompromised hosts.

Diagnosis of linitis plastica-type gastric adenocarcinoma by endoscopic ultrasound-guided fine needle aspiration: a case report.

BACKGROUND: The diagnosis of linitis plastica-type adenocarcinomas of the stomach has traditionally been made by brush cytology and mucosal biopsy. These techniques may yield false negative results due to the often submucosal location of these lesions. CASE: A 46-year-old woman presented witb epigaseric abdominal pain and loss of abbetite. Computed tomography of her abdomen revealed diffuse thickening of a portion of the gastric wall. Subsequent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the stomach yielded abundant single, discohesive malignant cells suspicious for lymphoma vs. poorly differentiated carcinoma. Special stains and immunohistochemical stains confirmed the diagnosis of poorly differentiated adenocarcinoma ofsignet ring cell type. CONCLUSION: As many linitisplastica-type adenocarcinomas are submucosal lesions, mucosal sampling by biopsy may yield nondiagnostic material in up to one third of cases. With its ability to sample deep submucosal lesions, EUS-FNA is an appropriate technique for establishing this diagnosis and guiding patient treatment.

Isolated intestinal neurofibromatous proliferations in the absence of associated systemic syndromes.

Gastrointestinal tract involvement by neurofibromatous lesions is rare and occurs most frequently as one of the systemic manifestations of generalized neurofibromatosis type 1 (NF1). In this setting, the lesions may manifest as focal scattered neurofibromas or as an extensive diffuse neural hyperplasia designated ganglioneuromatosis. Occasionally, such lesions may be the initial sign of NF1 in patients without any other clinical manifestations of the disease. Rarely, cases of isolated neurofibromatosis of the large bowel with no prior or subsequent evidence of generalized neurofibromatosis have been documented. We present the case of a 52 year-old female with abdominal pain and alternating bowel habits. Colonoscopic evaluation revealed multiple small polyps in the cecum and the presence of nodular mucosa in the colon and rectum. Pathologic evaluation of the biopsies from the cecum, descending colon, sigmoid colon, and rectum revealed tangled fascicles of spindle cells expanding the lamina propia leading to separation of the intestinal crypts. Immunohistochemical stains helped confirm the diagnosis of diffuse intestinal neurofibromatosis. A thorough clinical evaluation failed to reveal any stigmata of generalized neurofibromatosis. This case represents a rare presentation of isolated intestinal neurofibromatosis in a patient without classic systemic manifestations of generalized neurofibromatosis and highlights the need in such cases for close clinical follow-up to exclude neurofibromatosis type I or multiple endocrine neoplasia type II.

Cytologic diagnosis of alveolar soft part sarcoma of the lower extremity by fine needle aspiration and correlation with core biopsy: a case report.

BACKGROUND: Alveolar soft part sarcoma is a rare soft tissue tumor of uncertain origin that is generally slow growing but unmistakably malignant due to its propensity for metastasis to lung, bone and brain early in the course of disease. Fine needle aspiration biopsy (FNAB) of these tumors and recognition of the characteristic cytologic features precludes more invasive diagnostic measures and facilitates appropriate treatment. CASE: A 54-year-old African-American man presented to our institution with a 2-week history of left leg pain. Imaging studies revealed a left leg soft tissue mass just below the popliteal fossa and multiple bilateral lung lesions suggestive of metastatic neoplasm. FNAB of the left lower extremity mass yielded uniform clusters of cells and sigle cells with large nuclei and single prominent nucleoli. Histologically, the biopsy showed nests of large polygonal cells with abundant eosinophilic cytoplasm, round regular nuclei and prominent nucleoli. A periodic acid-Schiff (PAS) stain highlighted intracytoplasmic rhomboidal crystals, a feature diagnostic of alveolar soft part sarcoma. CONCLUSION: Alveolar soft part sarcoma may be diagnosed by its unique morphologic characteristics and should be considered in the differential diagnosis of all cytologically sampled soft tissue lesions.

Empyema necessitatis due to methicillin-resistant Staphylococcus aureus: case report and review of the literature.

Empyema necessitatis is a rare complication of empyema in which the pleural infection spreads outside of the pleural space to involve the soft tissues of the chest wall. Most cases of empyema necessitatis are related to Mycobacterium tuberculosis and, less commonly, to Actinomyces spp. and Streptococcus spp. Staphylococcus aureus has rarely been reported as the causative agent of empyema necessitatis, with the majority of S. aureus isolates being methicillin sensitive. Only two cases of empyema necessitatis due to methicillin-resistant S. aureus (MRSA) have been reported in the medical literature. We report the case of a 59-year-old Caucasian male who presented to our institution with complaints of pain in and swelling of his left upper chest of 2-months duration. A computed tomography scan of the chest showed an 8.1- by 6.5-cm lesion which extended from the left upper lobe of the lung into the extrathoracic soft tissues beneath the left upper pectoralis muscle. A wedge resection of the left upper lung lobe revealed lung tissue with an organized pneumonia-like pattern associated with marked acute pleuritis. Blood and urine cultures and cultures of the left chest soft tissue mass grew MRSA. The patient was successfully treated with vancomycin followed by a 10-day outpatient course of ciprofloxacin and trimethoprim-sulfamethoxazole. This case represents an extremely rare manifestation of an increasingly dangerous bacterial pathogen.

Kluyvera infections in the pediatric population.

In pediatric patients, Kluyvera spp. has emerged as a cause of disease ranging from soft tissue infections to sepsis with multiorgan failure. Successful treatment options include third-generation cephalosporins, tetracycline, aminoglycosides, and fluoroquinolones, but resistance to first- and second-generation cephalosporins persists. Clinicians should be aware of the spectrum of disease and increasing clinical importance associated with this emerging pathogen.

Neonatal Candida parapsilosis meningitis and empyema related to epidural migration of a central venous catheter.

Candida parapsilosis is an extremely rare cause of meningitis. We report the case of a neonate born at 26+4 weeks of gestation who was admitted to the neonatal intensive care unit at our institution due to respiratory immaturity. During the course of a 3-month hospitalization, the neonate developed fever and lethargy. A lumbar puncture revealed milky-white, turbid cerebrospinal fluid which contained many nucleated cells, mostly neutrophils. Microscopic examination of the cerebrospinal fluid revealed marked acute inflammation and fungal yeast forms, and cultures of the cerebrospinal fluid and peripheral blood yielded C. parapsilosis. Imaging studies subsequently revealed a subdural empyema related to epidural migration of a central venous catheter (CVL). The neonate received extended therapy with amphotericin B and fluconazole. He responded favorably to therapy and was discharged 3 months after birth. This case underscores the clinical importance of the recognition and treatment of a potentially lethal fungal pathogen of the central nervous system and the need for awareness of complications resulting from CVL malposition.

Neonatal respiratory tract involvement by Trichomonas vaginalis: a case report and review of the literature.

Only occasional cases of Trichomonas spp. infection have been reported in neonates, and these usually represent vaginal infections with Trichomonas vaginalis acquired during passage down the birth canal. We report the case of a 2-week-old girl who was brought by her mother to the Children's Emergency Clinic at our institution for symptoms of lethargy and poor appetite. The neonate was subsequently diagnosed with herpetic encephalitis and developed increasing respiratory difficulty, requiring intubation. Routine viral culture of a nasopharyngeal wash showed no viral organisms, but trichomonads were abundant microscopically on the viral culture medium. Molecular studies identified the organism as T. vaginalis. The significance of this organism as a neonatal respiratory pathogen and its contribution to neonatal respiratory distress are discussed.

Neisseria sicca meningitis following intracranial hemorrhage and ventriculostomy tube placement.

A normal component of the flora of the oropharynx, Neisseria sicca was first isolated in 1906 and has since been reported as a rare cause of various human infections including endocarditis, pneumonia, sinusitis, sepsis, and urethritis. We report the case of a 44-year-old African-American female with a history of hypertension who presented with complaints of right frontal headache, nausea, photophobia, and vomiting. A computed tomography scan of the patient's brain showed a large subarachnoid hemorrhage, and an arteriogram confirmed a large posterior communicating artery aneurysm. A ventriculostomy tube was placed, and the patient subsequently developed an elevated temperature and elevated white blood cell count. Cerebrospinal fluid studies showed elevated protein and glucose levels and cultures positive for N. sicca. This is only the seventh reported case of culture-proven meningitis related to N. sicca, and the first reported case associated with intracranial hemorrhage and ventriculostomy tube placement.