Listeria Monocytogenes: an uncommon pathogen of cervical necrotizing fasciitis.

The aim of this paper is to present a unique case of neck-necrotizing fasciitis caused by Listeria Monocytogenes in a young woman, successfully treated by surgery and IV antibiotic therapy. Necrotizing fasciitis is a rare, rapidly progressing and potentially life-threatening infection that infrequently occurs in the head and neck region. Pathogens involved in necrotizing fasciitis are heterogeneous and include aerobic and anaerobic bacteria. To the best of our knowledge, this is the only case of neck necrotizing fasciitis caused by Listeria Monocytogenes studied in literature so far.

Molecular impact of selective NFKB1 and NFKB2 signaling on DLBCL phenotype.

Diffuse large B-cell lymphoma (DLBCL) has been categorized into two molecular subtypes that have prognostic significance, namely germinal center B-cell like (GCB) and activated B-cell like (ABC). Although ABC-DLBCL has been associated with NF-κB activation, the relationships between activation of specific NF-κB signals and DLBCL phenotype remain unclear. Application of novel gene expression classifiers identified two new DLBCL categories characterized by selective p100 (NF-κB2) and p105 (NF-κB1) signaling. Interestingly, our molecular studies showed that p105 signaling is predominantly associated with GCB subtype and histone mutations. Conversely, most tumors with p100 signaling displayed ABC phenotype and harbored ABC-associated mutations in genes such as MYD88 and PIM1. In vitro, MYD88 L265P mutation promoted p100 signaling through TAK1/IKKα and GSK3/Fbxw7a pathways, suggesting a novel role for this protein as an upstream regulator of p100. p100 signaling was engaged during activation of normal B cells, suggesting p100's role in ABC phenotype development. Additionally, silencing p100 in ABC-DLBCL cells resulted in a GCB-like phenotype, with suppression of Blimp, IRF4 and XBP1 and upregulation of BCL6, whereas introduction of p52 or p100 into GC cells resulted in differentiation toward an ABC-like phenotype. Together, these findings identify specific roles for p100 and p105 signaling in defining DLBCL molecular subtypes and posit MYD88/p100 signaling as a regulator for B-cell activation.

Microgranular variant of acute promyelocytic leukemia in children.

PURPOSE: The microgranular variant (M3v) of acute promyelocytic leukemia (APL) rarely has been reported in a pediatric series of acute nonlymphoblastic leukemia (AnLL). We reviewed the clinical and biologic features of childhood M3v cases in our AnLL series. PATIENTS AND METHODS: From January 1970 to January 1991, 11 children with M3v were admitted and treated at our center. A diagnosis was made according to French-American-British (FAB) criteria. Morphologic examination, cytochemical analysis, and immunophenotyping were performed by a single pathologist. From January 1984, the diagnosis was confirmed by cytogenetic and, subsequently, by molecular analysis on frozen material. RESULTS: In our series, the overall incidence of children with APL was unusually high, 31.2% of the AnLL and M3v constituted one case in every four cases of APL. Even restriction of the analysis to the time when either cytogenetic and DNA studies confirmed the diagnosis, the incidence did not change. The immunophenotype of M3v cases was identical to that described for the hypergranular type, but an unexpected association of CD2 with M3v was shown. The onset was characterized by marked hyperleukocytosis (median WBC count, 87 x 10(9)/L) unlike classic APL. Disseminated intravascular coagulation (DIC) was always present and severe. Hyperleukocytosis and DIC were responsible for the high incidence of deaths for hemorrhagic events in the first days after onset (eight of 11 patients). CONCLUSIONS: In our experience, for unknown reasons, M3v may occur in childhood more than generally was considered. The clinical course and prognosis seem worse in M3v than in typical APL cases.

Evaluation of a new rapid immunoassay for the detection of Helicobacter pylori in faeces: a prospective pilot study.

BACKGROUND: Detection of Helicobacter pylori antigen in faeces is a valid method to diagnose H. pylori infection. Presently available stool tests are performed in the laboratory, and diagnostic report is delayed. AIM: To evaluate a new rapid stool test in a pre-treatment setting and to compare it with a validated laboratory stool test. METHODS: A total of 105 patients underwent gastroscopy with brush cytology, and biopsies for histology and rapid urease test, to assess H. pylori presence. Helicobacter pylori-status was considered positive if at least two tests were positive; negative if all tests were negative; indeterminate if one test was positive and two negative. Stool specimens were tested using either a rapid immunoassay kit (ImmunoCard STAT) or a laboratory enzyme immunoassay kit (Hp StAR). RESULTS: Sixty patients were infected with H. pylori, 44 non-infected, one indeterminate. The sensitivity and specificity of ImmunoCard STAT were 85 and 93%; those of Hp StAR were 88 and 100% (not significant). CONCLUSIONS: ImmunoCard STAT seems a reliable method for detecting H. pylori in untreated patients. It could replace laboratory stool tests, as it is easy and can be performed quickly. These characteristics might be a breakthrough for diagnosing H. pylori in the doctor's office.

Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial.

Amphotericin B, despite its intrinsic servere toxicity, is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy. The aim of this study was to show whether fluconazole was as effective as, and less toxic than, amphotericin, with no effort made to compare the antifungal activity of the two drugs. A group of 112 persistently febrile (> 38 degrees C) and granulocytopenic (< 1000 cells/mm3) cancer patients, not receiving any absorbable antifungal antibiotic for prophylaxis, with a mean age of 27 years (range 1-73 years), undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy, were randomised to receive either fluconazole (6 mg/kg/day up to 400 mg/day) or amphotericin B (0.8 mg/kg/day) as empirical antifungal treatment. Patients were required to have normal chest X-rays at randomisation, no previous history of aspergillosis and negative surveillance cultures for Aspergillus. The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients (75%) in the fluconazole group and in 37 of 56 (66%) in the amphotericin B group (P = 0.4). Duration of therapy was 6 days (95% CI = 4-8 days) in both groups. Death occurred in 3 patients (5%) in the fluconazole and in 2 (4%) in the amphotericin B group. No fungal death was documented in either group. Adverse events developed in 18 of 56 patients (32%) in the fluconazole group and in 46 of 56 (82%) in the amphotericin B group (P < 0.001). In the amphotericin B group, 5 patients had treatment discontinued because of toxicity, versus none in the fluconazole group, a difference which approached statistical significance (P = 0.06). This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B, in pragmatical terms and for this specific indication. However, numbers are too small to allow definitive conclusions about efficacy, and the use of fluconazole for this indication remains experimental. Future studies should try to identify patients more at risk of fungal infections, with the aim of individualising antifungal approaches.

Chronic abdominal pain and depression. Epidemiologic findings in the United States. Hispanic Health and Nutrition Examination Survey.

We report data on abdominal pain and depression from a survey of Hispanic Americans by the United States National Center for Health Statistics. The point prevalence rates of chronic abdominal pain were 4.6% in Mexican Americans and 5.8% in Cuban Americans in a total of 4175 subjects. The rate was 8.3% among 1323 Puerto Ricans. In 53% the abdominal pain came in waves. Using the Depression scale of the Center for Epidemiologic Studies (CES-D), 18.7% of Mexican and Cuban Americans with pain were found to be depressed to an extent likely to require intervention, and 40.8% of Puerto Ricans were so affected. The Diagnostic Interview Schedule (DIS) gave more conservative figures for major depression in terms of DSM-III, viz., 6.8% for Mexican and Cuban Americans with chronic pain, and 12.6% for Puerto Ricans with chronic pain. Logistic regression analyses demonstrated links between depression and female sex, the single state, low education and income, and chronic abdominal pain. The most consistent relationships for depression were with chronic pain, female sex and the single state. The results confirm the strong relationships between chronic pain, mood and female gender, and other socio-demographic variables.

The immortalized UROtsa cell line as a potential cell culture model of human urothelium.

The UROtsa cell line was isolated from a primary culture of normal human urothelium through immortalization with a construct containing the SV40 large T antigen. It proliferates in serum-containing growth medium as a cell monolayer with little evidence of uroepithelial differentiation. The working hypothesis in the present study was that this cell line could be induced to differentiate and express known features of in situ urothelium if the original serum-containing growth medium was changed to a serum-free formulation. We demonstrated that the UROtsa cells could be successfully placed into a serum-free growth medium consisting of a 1:1 mixture of Dulbeco's modified Eagle's medium and Ham's F-12 supplemented with selenium (5 ng/mL), insulin (5 microg/mL), transferrin (5 microg/mL), hydrocortisone (36 ng/mL), triiodothyronine (4 pg/mL), and epidermal growth factor (10 ng/mL). Under serum-free growth conditions, confluent UROtsa cells were shown by light microscopy to produce raised, three-dimensional structures. Routine ultrastructural examination disclosed these three-dimensional areas to consist of a stratified layer of cells that strongly resembled in situ urothelium. The cells displayed numerous desmosomal connections, complex interactions of the lateral membranes, and abundant intermediate filaments within the cytoplasm. Freeze fracture analysis demonstrated that the cells possessed tight-junction sealing strands and gap junctions. The overall morphology was most consistent with that found in the intermediate layers of in situ urothelium. The basal expression patterns of the metallothionein (MT) and heat shock proteins 27, 60, and 70 were determined in these cells, and expression was in agreement with that known to occur for in situ urothelium. The cells were also successfully tested for their ability to be stably transfected using expression vectors containing the MT-3 or MT-2A genes. The findings suggest that the UROtsa cells grown with a serum-free medium could be a valuable adjunct for studying environmental insult to the human urothelium in general and for the stress response in particular.

Pulmonary infections in lung cancer patients at diagnosis.

We carried out a prospective study involving 96 consecutive lung cancer patients at diagnosis, in order to determine through quantitative cultures of the bronchoalveolar lavage (BAL) fluid, the prevalence of pulmonary infections; we also evaluated the relationship between a patient's performance status, immunocompetence, lung cancer stage, histotype and the occurrence of respiratory infections. The patients (81 males, 15 females) had a mean age of 64 +/- 9 years. Of these, 62 were smokers, 30 were ex-smokers and four had never smoked. Sixty-seven patients had a prior history of chronic bronchitis. A total of 42 micro-organisms were cultured from the BAL fluids of 33 patients (34.3%). Fifty percent of these micro-organisms were gram-negative, 33.3% were gram-positive and the remaining 16.7% were other micro-organisms. The bacilli most often isolated were the Haemophilus species, accounting for 38.8% of all gram-negative bacilli. The most frequently isolated gram-positive pathogen was the Staphylococcus aureus. We have not found a significant relationship between the presence of a respiratory infection and the different cell types separately analyzed, nor with SCLC and NSCLC patient groups, nor with the stage of the disease. The performance status, the immunoregulatory ratio and the lymphocyte subsets were not significantly different in patients with or without a pulmonary infection. We think that the identification of a definite etiologic agent is of great importance for a rational anti-microbial treatment of pulmonary infections.

Fluorescence studies on the age related changes in bovine and human lens membrane structure.

Bovine and human lens fiber cell plasma membranes were isolated as the urea-insoluble fraction for a study of age related changes. The changes in fluorescence intensity, both intrinsic (tryptophan) and extrinsic probes ANS (1-anilinonaphthalene-8-sulfonic acid) and DPH (1,6-diphenyl 1,3,5-hexatriene), as well as DPH anisotropy and lifetime were measured. The results of tryptophan fluorescence indicate that tryptophan residues in membrane proteins are in a very hydrophobic environment and do not show a change with aging. ANS reacts with surface protein in the polar-apolar interface, while DPH penetrates into the interior of membranes. Both probes show a decrease in fluorescence intensity in the old membranes. The decrease in ANS fluorescence may result from the conversion of MP26 to MP22, while the decrease of DPH fluorescence intensity may indicate a decrease in accessibility of lipid to DPH. To further delineate the change, fluorescence anisotropy and lifetime data of the lipid probe DPH were obtained. While lifetimes do not change with age, anisotropy shows a definite age-dependent increase. Anisotropy is related to the degree of lipid structural order. Greater anisotropy values were found for older membrane samples, indicating an increased rigidity with age, which may be partially caused by the increased cholesterol/phospholipid (C/P) ratio as reported in the literature.

[Incidence of giardiasis in adults patients with acute enteritis]. / Incidenza della giardiasi in pazienti adulti con enterite acuta.

The Authors report the findings of a perspective study carried out in 214 cases of acute diarrhoea to estimate the presence of giardia intestinalis infections. The incidence of 3.2% has been discussed on the bases of recent epidemiological advances.

Neonatal bacterial meningitis.

Neonatal bacterial meningitis (NM) continues to be a serious disease with an unchanging rate of adverse outcome of 20-60%, despite a worldwide decline in mortality. The 3 major pathogens in developed countries are: Group B streptococcus, gram negative rods and Lysteria monocytogenes. Signs and symptoms of NM may be subtle, unspecific, vague, atypical or absent. In order to exclude NM, all infants with proven or suspected sepsis should undergo lumbar puncture. Positive culture of cerebrospinal fluid may be the only way to diagnose NM and to identify the pathogen, as CSF parameters Smay be normal at early stages and NM may occur frequently (up to 30% of cases) in the absence of bacteraemia. When NM is suspected, treatment must be aggressive, as the goal is to achieve bactericidal concentration of antibiotics and to sterilize CSF as soon as possible. Antibiotics should be administered intravenously, at the highest clinically validated doses. Empiric antibiotic treatment should include agents active against all main pathogens; currently the recommended empiric treatment of NM is ampicillin, plus an aminoglycoside and a third-generation cephalosporn. Therapy should be reassessed after cultures and antibiotic susceptibility is available. Prevention of neonatal sepsis, early recognition of infants at risk, prompt treatment and future adjunctive therapies will improve prognosis. Finally, we present the first preliminary Italian data on GBS meningitis. Data are obtained from an area-based study conducted In Emilia-Romagna during 2003 to 2009.

Ceftriaxone kinetics after a single intravenous dose in leukemic children with fever and granulocytopenia.

Ceftriaxone (CFX) is a new third-generation cephalosporin with interesting characteristics as regards both its antibacterial spectrum and kinetics which make it potentially useful in the empiric treatment of infections in neutropenic cancer patients. However, since its kinetic characteristics in children with leukemia are not known and its pharmacokinetics are reported to be altered in such patients, we studied ceftriaxone's activity in ten leukemic children with fever and neutropenia. Our findings seem to be confirm the potential efficacy of the drug also in this particular type of patient.

[Current epidemiological and clinical features meningitis in a northern Italian area] / Attuali aspetti epidemiologici e clinici delle meningiti in un'area del nord Italia.

Objectives: To study etiological, epidemiological and clinical features of 97 cases of acute meningitis. Methods: Ninety-seven cases of acute meningitis were examined in adult HIV-negative patients admitted to the Infectious Diseases Unit of the Azienda Ospedale-Universita S. Anna in Ferrara. Demographic, etiological, epidemiological and clinical data were analyzed. Results: All cases were divided into two groups according to the macroscopic aspect of cerebrospinal fluid (CSF): purulent CSF (50 cases) or non-purulent CSF (47 cases). Purulent CSF meningitis more frequently affected male patients (64% vs 47%) and older patients (average 52 vs 44 years). The main epidemiological features in both groups were underlying bacterial diseases (i.e. otomastoiditis and/or sinusitis in 50% of pneumococcal meningitis) and iatrogenic immunodeficiency. From a clinical point of view the following alterations in the state of consciousness (stupor, confusion and coma) were most frequently found in purulent meningitis. The following non purulent forms of meningitis were diagnosed: 5 tubercular, 3 viral infections, 2 by Listeria monocytogenes, 1 by Entoameba histolytica, 1 by Cryptococcus neoformans and 35 (74,4%) unknown causes. Purulent meningitis were: 20 (40%) Streptococcus pneumoniae, 10 Neisseria meningitidis, 3 Staphylococcus aureus, 2 Escherichia coli, 1 Haemophilus influenzae and 1 Pseudomonas aeruginosa; 13 cases were unidentified. From 1989 to 1993 and from 1994-98 both groups of meningitis increased; respectively from 17 to 30 cases for non-purulent meningitis and from 18 to 32 cases for purulent meningitis. Meningitis due to Streptococcus pneumoniae increased from 27.7% to 46.8% during the period 1994-98. Conclusions: The study shows the high incidence of pneumococcal meningitis, during 1994-98, because a large number of patients with sinusitis and otomastoiditis were observed. The incidence of meningococcal meningitis appears stable. These data confirm the importance of timely diagnosis and correct therapy for such infections with reserved prognosis.

[Respiratory circuits and infections of the airway]. / Circuiti dei respiratori e infezioni delle vie aeree.

OBJECTIVE: To study the effects of ventilator circuit changes on the rate of airway infections and to investigate the relationship between the microorganisms responsible for circuit colonization and those responsible for infection. DESIGN: Prospective study, carried out in two different periods, of one year duration each. SETTING: General Intensive Care Units (ICUs) in a University Hospital. PATIENTS: Seventy-eight patients, requiring mechanical ventilation (VAM) for more than 5 days, were enrolled. They were divided into two groups: in the first (group I, n. 36, 1st period) the ventilator circuit was changed every 5 days; in the second (group II, n. 42, 2nd period) every 10 days. INTERVENTION: Ventilator circuit change every 5 or 10 days. Daily culvert and filling of cascade humidifiers with sterile irrigation water. Daily replacement of mount catheter. MEASUREMENTS: Qualitative cultures of tracheobronchial aspirate and of fluid from the humidifying cascades and the expiratory tubing traps. RESULTS: The two groups were similar. Pneumonia and tracheobronchitis were found in the 25% and 11% of patients of group I and in 26% and 12% of those of group II respectively. The VAM duration was 26.5 +/- 15 days in patients who developed airway infection, and 12.9 +/- 11.6 days (p < 0.001) in patients who did not. The Gram+ organisms were predominant. An identical microorganism was found both in the tracheo-bronchial aspirate and in the circuit in 44 of 78 (56%) patients; no difference was found between infected (16 of 29) and non infected (28 of 49) patients. CONCLUSIONS: Changing the ventilator circuit every 10 days rather than every 5 days, does not increase the incidence of airway infections and result in considerable savings in the expenses of tubing and personnel time. The infection or colonization rates due to the same microorganisms are quite low and it seems not useful to make routine cultures of fluid from humidifying cascades and the expiratory tubing traps in order to characterize in time the microorganism that could be responsible of airway infections.

[Microbiologic flora in two different periods in intensive care units]. / Indagine microbiologica in due diversi periodi di degenza in rianimazione.

Bacterial examinations performed in two periods (Nov. 1985-Feb. 1986) and Nov. 1988-Feb. 1989) on materials taken from patients admitted into two similar Intensive Care Units (ICU) of the same hospital were evaluated. Excluding oropharyngeal swab cultures, which were performed only in the second period, Gram positive bacteria were 45.3% in 1985-1986 and 62.3% in 1988-1989 and Gram negative fell from 41.9% to 29%. The percentage of fungi remained unchanged. Microorganisms did not grow in 33.3% of tracheal aspirate specimens in 1985-1986 and in 54.3% in 1988-1989, probably depending on the larger number of patients with decompensated chronic respiratory failure treated in the second period. Usually the microorganisms found in the trachea was also in the oropharynx; Gram negative were only 5.1% of the microorganism collected in the oropharinx. The authors emphasize the increase of Gram positive bacteria in ICUs and suggest that the low rate of pneumonia observed in this study depends mostly on the good neurologic state of their patients.

Isolated testicular relapse in a boy with acute lymphoblastic leukemia following allogeneic bone marrow transplantation.

About 5-10% of boys with acute lymphoblastic leukemia (ALL) present with isolated testicular relapse. Very frequently these relapses occur during treatment or in the following six months, and in these cases the prognosis is very severe. The patients are usually treated with radiotherapy and chemotherapy or bone marrow transplantation (BMT). Testicular relapses after BMT are relatively rare. We report the case of a child with ALL who presented testicular relapse during therapy and was treated with local radiotherapy (2000 cGy), chemotherapy and allogeneic matched BMT. The preparative regimen consisted of Cyclophosphamide (60 mg/kg/day x 2 days) and total body irradiation (200 cGy x 2/day x 3 days). Engraftment was documented at day + 14. The patient presented again with testicular relapse at day + 146, and was therefore treated with orchiectomy, local radiotherapy and systemic chemotherapy. A marrow relapse followed, however, at day + 284 and the patient died of progressive disease.