Detection of particle motion using image processing with particular emphasis on rolling motion.

Image-processing has been used in granular systems for detecting particle positions and motion near optically accessible surfaces like sediment flow and bedload transport. We review the image-processing techniques used for single and multiple particles. To enhance reliability in particle recognition, tools like Canny edge and Hough transform are intensively used. We show exemplarily how they can be applied to detect not only particle positions but also rotatory motion. The different steps are described in detail and the algorithm is applied to different examples, which are discussed in view of the obtained accuracy.

Posterior wall as atypical localization of left atrial myxoma : Diagnosis and management.

Atrial myxomas are the most common benign cardiac neoplasms. Although the majority occur in the left atrium (LA) and are attached to the interatrial septum (75-80 % of cases), they can arise from any part of the LA and the cardiac chambers. We report the case of a 65-year-old woman who presented with features of worsening dyspnea and persistent headache. During transthoracic echocardiography, a suspected cardiac myxoma was found arising from the posterior wall of the LA.

Polyclonal intravenous immunoglobulin: an important additional strategy in sepsis?

Sepsis syndrome is characterized by a systemic inflammatory response to infection potentially leading to acute organ failure and rapid decline to death. Polyclonal intravenous immune globulin, a blood product derived from human donor blood, in addition to antiinfective activities, also exerts a broad antiinflammatory and immunomodulating effect. Intravenous immunoglobulin (IVIg) has been proposed as adjuvant therapy for sepsis even though the clinical studies demonstrating their efficacy and safety are relatively small. Several systematic reviews and meta-analyses of intravenous immunoglobulin treatment in sepsis have been performed. As a result of heterogeneity across studies and inconsistencies in results, the majority have concluded that more evidence, coming from large, well-conducted randomized controlled trials (RCTs), is required. Moreover the appropriate timing of administration and the identification of specific clinical settings represent a key factor to maximizing their beneficial effect. The authors, in this revision, review the basic mechanisms of action of IVIg, the rationale for their use, and their clinical applications.

Intra-abdominal versus free-loop portion Doppler analysis of the umbilical artery: the importance of the choice.

AIM: The aim of this study was to assess the variations in Doppler indexes along the length of the cord from the intra-abdominal portion (IAP) to the free loop portion (FLP) of the umbilical artery (UA). METHODS: UA blood flow velocities were measured at the IAP and FLP in 100 low-risk singleton pregnancies. The peak systolic velocity (PSV), end-diastolic velocity, pulsatility index (PI), resistance index (RI), PS/ED ratio and Delta value (Δ) were calculated. at each site of sampling and were compared. RESULTS: PI and RI of the IAP were greater versus the FLP. UA blood velocities increased with gestational age and the PSV at the IAP showed different development compared to other sites, increasing from 20 to 30-32 weeks and then decreasing until term. The PSV value was greater in the IAP from 20 until 36 weeks. There were not significant differences in EDV values between the two sites. The Δ PI in IAP remained constantly greater than ~0.2 at all gestational ages. CONCLUSION: UA Doppler parameters vary significantly at different locations, showing the greater value in the IAP. The IAP site is in a fixed anatomical position, therefore potentially reproducible. This potential advantage is very important in cases of severe growth restriction and in monoamniotic twins.

Prokaryotic division interactome: setup of an assay for protein-protein interaction mutant selection.

A method which enables selection of protein mutants impaired in their ability to interact with their normal protein partners is presented here. The method is the two-phage two-hybrid assay adapted for mutant selection. In the two-phage assay, the interaction between two proteins enables the formation of a functional hybrid lambdoid repressor that shuts down expression of a reporter gene governed by a chimeric promoter/operator region. To adapt the assay to interaction mutant selection, antibiotic resistance was used as a reporter gene. In this case, the interaction between the two proteins resulted in antibiotic sensitivity, whereas the loss of interaction conferred resistance to the bacterial strain. Therefore, turning on reporter gene expression highlights the loss of interaction due to a mutation in one of the genes for the two protein partners, and leads to direct selection of the mutants regardless of the mutant phenotype. In this paper, application of this method to isolation of interaction mutants in proteins involved in Escherichia coli K12 cytokinesis is reported.

Can immune disorders influence therapeutic approaches in treatment of epilepsy among neurologists? A first cooperative national recognition in Italy.

Functional disturbances of the immune system have been detected more often among persons affected by epilepsy than in the general population. In the February-July period of 2007 a specific questionnaire on the relationship between epilepsy and immunological response was sent to 27 specialized Centres for Epilepsy in nine Italian regions. 15,388 epileptic patients attended twenty-seven Centers during this six-month period. 3.3 percent (n=502) of these patients suffered an immune disease. This is the first National survey on the relationship between epilepsy and immunological response in current clinical practice.

Long-term mechanical support with the HeartMate II LVAS.

BACKGROUND: The use of left ventricular assist devices (LVAD) is an accepted therapy for patients with refractory heart failure. The HeartMate II is a small (350 g), implantable, axial-flow pump (nonpulsatile flow), which is designed to support the left ventricle for extended periods of time. Here we have reported our initial single-center clinical experience with this device as a bridge to heart transplantation. MATERIALS AND METHODS: Between March 2002 and December 2008, 18 transplantable adult patients were supported on long-term HeartMate II LVAS at our institution. The cohort included 15 men with an overall mean age of 52 +/- 8.4 years (range, 31-64 years). Primary indications for implantation were ischemic cardiomyopathy (CMP; n = 13) and idiopathic CMP (n = 5). All heart failure patients were New York Heart Association (NYHA) functional class IV. None of them had undergone prior open heart surgery. Implantation was performed via cannulation of the left ventricular apex and ascending aorta, and in each case was an elective procedure. RESULTS: Mean support time was 217 +/- 212.3 days (range, 1-665 days). Early (30-day) mortality was 27.7% (n = 5) due to multiple organ failure and sepsis as main causes of death. Bleeding requiring reoperation occurred in 6 cases (33.3%). Cerebral hemorrhage occurred in 1 case. There were 2 driveline infections and no device failure. Twelve subjects (66.6%) were successfully discharged home. Overall, 9 patients (50%) underwent transplantation and 3 are awaiting a suitable organ (2 were discharged home and 1 is in hospital). At latest follow-up, the survival rate after heart transplantation was 66.6% (n = 6). CONCLUSIONS: Long-term HeartMate II LVAS can successfully bridge patients to heart transplantation. Good mid- and long-term results may support the use of this device even for a permanent solution in nontransplantable subjects.

Are glucocorticoids a consistent risk factor for infections in rheumatoid arthritis patients under treatment with methotrexate and etanercept?

OBJECTIVE: To evaluate the incidence of infections in subjects with rheumatoid arthritis (RA), treated with an anti-TNFalpha blocker during one year follow-up. The aim of the study was focused to evaluate the number of infectious episodes in two groups of patients treated with etanercept (ETN) plus methotrexate (MTX) or ETN plus MTX and glucocorticoid drugs (GCs/prednisone) for a 12 months period. MATERIALS AND METHODS: Sixty-nine out of 122 RA patients treated with an anti-TNFalpha drug (ETN) were included in an outpatient control system within the Immunology Department Sapienza-University of Rome-II; School of Medicine. RA patients were studied during the first year after ETN introduction. Particularly 20 RA patients have been included in a subgroup. For these 20 patients infections have been monitored for 2 years: 12 months before and 12 months after ETN treatment starting. RESULTS: According to drugs administration protocols, after a careful screening aiming to exclude latent tuberculosis infection, 20 patients have been treated with ETN (10 of them received treatment in association to MTX, while 10 were given a GCs therapy plus MTX). During the one-year ETN treatment period, 7 infections have been described in the group treated with ETN, MTX and GCs and no infection in the group treated with ETN and MTX. After analysing the infection number in the two groups of patients, in the year preceding biological treatment no significant change arose. CONCLUSIONS: The risk of infections in subjects treated with the biological drug ETN is well known. Our data show that after one year therapy the [ETN+MTX+GCs] group is marked by a greater frequency of infectious episodes compared to the subjects treated with ETN plus MTX. Therefore, the additional infectious risk appears to be related to steroid therapy itself, though infections were not serious.

Intravenous IgG: biological modulating molecules.

Intravenous IgG has been adopted as treatment for various immune-related diseases, including immune thrombocytopenic purpura, autoimmune neuropathies, systemic lupus erythematosus, Guillain-Barré syndrome, myasthenia gravis, Kawasaki disease, skin blistering diseases. The intravenous administration of exogenously pooled human immunoglobulin was originally licensed as antibody replacement therapy in patients with primary immunodeficiencies, but in the last thirty years, despite a current lack of institutional approval, off-label IVIgG treatment of a consistent number of disorders has shown to be a useful approach with good clinical results. The mechanism of action of IVIgG is complex and is not fully understood. The current understanding and development in the immune modulant action of IVIgG has three basic mechanisms: 1) F(ab')2 mediated actions; 2) interaction of IgGFc molecule with Fc receptors (FcgammaR); 3) actions mediated by complement fractions binding within the Fc molecular structure. The mode of action of IVIgG involves expression and function of Fc receptors, idiotype network, complement and cytokine network, T and B cell differentiation, modulation of antigen-presenting cells (APC). The therapeutic action of IVIgG is also related to natural antibodies in maintaining immune homeostasis. In addition, IVIgG interaction through V regions with complementary V regions of antibodies may provide a rational basis for selection of various immune repertoires. Since there is a significant gap between the institutional approval and the use of IVIgG in various clinical conditions, for which there is no adequate testing or for which a small number of records does not allow a rigorous statistical approach, several public and private institutions (mostly insurance companies) and research centres have developed guidelines for evaluating a rational and deontological approach in various pathological situations where IVIgG is used. Mathematical models based on non-linear differential equations may represent another potentially useful system to better understand an IVIgG targeted use in individual subjects.

[Pharmacological induction of labour: benefits and risks]. / Induzione farmacologica del travaglio di parto: vantaggi e rischi.

AIM: Induction of labour is a very common practice in modern obstetrics. The most used method is based on the use of topical prostaglandins. In this study we aimed to analyse the results of pharmacological induction of labour through the use of dinoprostone, comparing the intracervical gel (Prepidil 0.5 mg) and the vaginal insert (Propess 10 mg). METHODS: An observational longitudinal study was conducted, in which all patients treated with prostaglandins from January 1, 2003 to June 30, 2006 were included, for a total of 852 cases. The intracervical gel was applied on 32.5% of pregnant women (277 patients) while the vaginal insert to 56.2% (479 patients); in 11.3% of the cases (96 patients) both preparations were administered, one after the other. RESULTS: In 2/3 of the total (568 patients), the induction led to vaginal delivery, in contrast to 284 cases in which the practice showed negative results: in 270 women (31.7%) a cesarean section was practiced. Adverse events occurred only in 1.8% of cases (16 patients); the most frequent adverse reaction was uterine hypertonus in 1.8% of cases, which was in any case resolved with removal of the vaginal insert or injection of a tocolytic drug (atosiban). CONCLUSION: Induction through prostaglandins is an effective and safe method to get cervical maturation. Its success is influenced by Bishop score. In the case of unfit cervix, vaginal insert seems to get better results than intracervical gel. The relation between risks and benefits is certainly better in the latter.

Biased T-cell receptor repertoires in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).

Chromosome 22q11.2 deletion (del22q11.2) syndrome (DiGeorge syndrome/velocardiofacial syndrome) is a common syndrome typically consisting of congenital heart disease, hypoparathyroidism, developmental delay and immunodeficiency. Although a broad range of immunologic defects have been described in these patients, limited information is currently available on the diversity of the T-cell receptor (TCR) variable beta (BV) chain repertoire. The TCRBV repertoires of nine patients with del22q11.2 syndrome were determined by flow cytometry, fragment size analysis of the third complementarity determining region (CDR3 spectratyping) and sequencing of V(D)J regions. The rate of thymic output and the phenotype and function of peripheral T cells were also studied. Expanded TCRBV families were detected by flow cytometry in both CD4+ and CD8+ T cells. A decreased diversity of TCR repertoires was also demonstrated by CDR3 spectratyping, showing altered CDR3 profiles in the majority of TCRBV families investigated. The oligoclonal nature of abnormal peaks detected by CDR3 spectratyping was confirmed by the sequence analysis of the V(D)J regions. Thymic output, evaluated by measuring TCR rearrangement excision circles (TRECs), was significantly decreased in comparison with age-matched controls. Finally, a significant up-regulation in the percentage, but not in the absolute count, of activated CD4+ T cells (CD95+, CCR5+, HLA-DR+), IFN-gamma - and IL-2-expressing T cells was detected. These findings suggest that the diversity of CD4 and CD8 TCRBV repertoires is decreased in patients with del22q11.2 syndrome, possibly as a result of either impaired thymic function and/or increased T-cell activation.

Impaired nutritional status in common variable immunodeficiency patients correlates with reduced levels of serum IgA and of circulating CD4+ T lymphocytes.

BACKGROUND: Common variable immunodeficiency (CVI) is a primary defect of the immune system. Infections, persistent diarrhoea and malabsorption may result in malnutrition, which may in turn contribute to increased morbidity. In this paper, the prevalence of malnutrition in CVI was evaluated. PATIENTS AND METHODS: Forty CVI patients (20 male, 20 female, aged 17-75 years) underwent anthropometric measurements from which body mass index, arm fat and muscle area were calculated. Body mass index values < 18.5 and arm fat and muscle area values < 10th percentile were considered indicative of malnutrition. Patients were divided into four groups according to circulating CD4+ T cells (lower or greater than 300 microL(-1)) and serum immunoglobulin A (IgA) levels (detectable and undetectable). RESULTS: Body mass index < 18.5, arm fat and muscle area < 10th percentile were observed in 23%, 58% and 44%, respectively, of patients. Lower values of body mass index, arm fat and muscle area were more frequent in patients with low CD4+ cells and undetectable IgA. Low arm fat values were more frequent in patients with diarrhoea (P = 0.03). Infectious episodes were more frequent in undetectable IgA than in detectable IgA patients (P = 0.04). CONCLUSIONS: Anthropometric measurements revealed an increased rate of malnutrition in CVI patients, particularly in those with low CD4+ and undetectable IgA, suggesting that selected CVI subjects could be considered for standard or specialized nutritional support.

Molecular and cytogenetic remission in a case of subtype M4E acute myelogenous leukemia with minimal monochemotherapy: high sensitivity or spontaneous remission?

Complete remission was observed in an adult patient with acute myelogenous leukemia after minimal monochemotherapy. Remission occurred after a severe febrile pneumonia and was accompanied by cytogenetic and molecular remission. The hypothesis of spontaneous remission was raised, even if a high sensitivity to low-dose cytostatics cannot be excluded. Such spontaneous complete remissions, often associated with bacterial infections and blood transfusions, are extremely rare, and are usually of short duration. Previous cases are summarized, and the role of etiologic factors is discussed.

Acute myeloblastic leukemia secondary to myelodysplasia (MDS-AML): a comparison of remission induction with three drugs versus standard two-drugs induction.

To evaluate the addition of a third drug to standard induction chemotherapy in patients with MDS-AML, 23 patients (males/females 13/10, median age 54.3 years, range 24-74 years, median MDS duration 9.8 months, range 2-39 months) who received a standard 2-drugs induction were compared with 23 patients (males/females 11/12, median age 45.6 months, range 21-60 years, median MDS duration 8.3 months, range 2-29 months) who received an intensified 3-drugs induction with etoposide. CR rate, median CR duration and median OS were similar in both groups (48% vs 56%, 4.8 vs 5.9 months, 6.5 vs 7.0 months respectively). Among responding patients, all but one, who underwent allogeneic bone marrow transplantation, relapsed. In conclusion, addition of a third drug (etoposide) does not seem to significantly improve the poor prognosis of MDS-AML patients.

Nitric oxide donors in pregnancy: fetomaternal hemodynamic effects induced in mild pre-eclampsia and threatened preterm labor.

OBJECTIVE: The present study was performed to determine whether there are significant differences in the effects of the nitric oxide donor, glyceryl trinitrate, administration in pregnancies complicated by mild pre-eclampsia compared to the effects in pregnancies which are uncomplicated by this pathology. Glyceryl trinitrate is able to release nitric oxide (NO); deficiency of NO has been hypothesized in the pathogenesis of pre-eclamptic disorders. METHODS: In this prospective study, ten patients with threatened preterm labor and ten patients with mild preeclampsia were studied at around 30 weeks of pregnancy. The maternal blood pressure, maternal heart rate, fetal heart rate and flow velocity waveforms of the placental uterine artery, umbilical artery and fetal middle cerebral artery, evaluated by means of color Doppler and pulsed Doppler, were recorded before and 10, 20 and 30 min after the sublingual administration of 0.3 mg of glyceryl trinitrate or placebo. The pulsatility index (PI) was calculated. The percentage change from the control period (delta %) was calculated for each parameter at 10, 20 and 30 min. Ten normal pregnant women at the same gestational age were used as controls and were administered a placebo. RESULTS: The maternal blood pressure recorded as systolic and diastolic values, demonstrated a significant decrease in the pre-eclampsia group after glyceryl trinitrate administration; the delta % at any time considered was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the placental uterine artery showed a significant decrease in both groups after 20 and 30 min from drug administration; the delta % at 20 and 30 min was significantly higher in the pre-eclampsia group than in the threatened preterm labor group. The PI of the umbilical artery showed a significant decrease after 30 min from the glyceryl trinitrate administration. The fetal heart rate showed no significant variations during the study in either group. The PI of the fetal middle cerebral artery showed no significant variations during the study in either group. No parameter was changed in the control group. CONCLUSION: Glyceryl trinitrate administration was followed by a greater reduction of the resistance to blood flow in the fetoplacental circulation of the pregnancies affected by mild pre-eclampsia compared to pregnancies uncomplicated by this pathology. This effect can be attributed to the NO released by the drug which offsets the decreased production of NO, postulated to contribute to the pathogenesis of pre-eclampsia.

Immune-derived cytokines in the nervous system: epigenetic instructive signals or neuropathogenic mediators?

The investigation of the effects of inflammatory cytokines (IC) on the growth and differentiation of neural cells has provided new insights on the role of such soluble mediators in nervous system development and/or plastic remodeling as well as in the pathogenesis of inflammatory neurodegenerative disorders, which are characterized by chronic IC dysregulation in the central nervous system (CNS). Thus, the study of the interaction between CNS and immune-derived soluble signals in physiological or pathological conditions is of increasing interest. This review first discusses experimental evidence supporting the instructive/permissive role of immune-derived cytokines on CNS development and plasticity. Next, we focus on human neurological disease states such as multiple sclerosis and the neurodegeneration associated to the acquired immune deficiency syndrome in which different inflammatory cytokines have been proposed as potential neuropathogenic mediators.

Gastric pathology in patients with common variable immunodeficiency.

BACKGROUND/AIMS: Common variable immunodeficiency (CVID) is an immunological disorder characterised by defective antibody production. Patients with CVID have a high risk of gastric cancer. It has been suggested that gastric cancer results from an interaction between environmental factors and a genetic predisposition. The role of Helicobacter pylori as an environmental factor in gastric carcinogenesis is of current interest. Moreover, p53 gene mutations have been reported in gastric cancer. This study focuses on the gastric pathology of patients with CVID and correlation with H pylori infection. METHODS: Thirty four consecutive dyspeptic patients with CVID (mean age 49.6 years, range 14-72; 17 men) were included in the study. An upper gastrointestinal endoscopy was performed and biopsy specimens were taken from the antrum, incisura angularis, and gastric body. Biopsies were used for histological assessment, to identify the presence of H pylori, and to evaluate p53 overexpression. RESULTS: H pylori infection was detected in 14/34 (41%) patients. Chronic active gastritis involving both antrum and body was observed more frequently in H pylori positive (79%) than H pylori negative (20%) patients (p = 0.001). Similarly, a histological feature of multifocal atrophic gastritis was found more frequently in infected (50%) than uninfected patients (10%) (p = 0.012). In addition, one case of gastric adenocarcinoma and another of notable dysplasia were observed in the H pylori positive group. Overexpression of p53 was found in six (18%) patients, including one with normal gastric mucosa. CONCLUSIONS: It can be hypothesised that both H pylori and p53 alterations play a role in the gastric carcinogenesis of patients with CVID.

Inflammatory cytokines and HIV-1-associated neurodegeneration: oncostatin-M produced by mononuclear cells from HIV-1-infected individuals induces apoptosis of primary neurons.

Neurologic abnormalities are common in HIV-1-infected patients and often represent the dominant clinical manifestation of pediatric AIDS. The neurological dysfunction has been directly related to CNS invasion by HIV-1 that is principally, if not exclusively, supported by blood-derived monocytes/macrophages and lymphocytes. By using primary long term cultures of human fetal sensory neurons as well as sympathetic precursors-like neuronal cells, we determined that blood-derived mononuclear cells from HIV-1-infected individuals spontaneously release soluble mediators that can potently inhibit the growth and survival of developing neurons as well as the viability of postmitotic neuronal cells by inducing apoptotic cell death. Analysis of the cytokines produced by lymphomonocytic cells, HIV-1 infected or activated, indicated that oncostatin M (oncM) is a major mediator of these effects. Since low TGF-beta1 concentrations were capable of enhancing oncM-mediated neuronal alterations, our data indicate that by acting in concert with other cytokines, oncM may induce neuronal demise in both the developing and the mature brain. Thus, this cytokine may contribute to the setting of the neuronal cell damage observed in HIV-1-infected individuals.

Use of voriconazole in treatment of Scedosporium apiospermum infection: case report.

We report a case of disseminated Scedosporium apiospermum infection in a neutropenic patient with acute myeloid leukemia. Due to progression of the mycosis after 7 days of amphotericin B lipid complex therapy and to high susceptibility of the mold to voriconazole in vitro, the patient was treated with intravenous voriconazole. After a few days of therapy, fever disappeared and skin lesions improved. However, the patient died after 1 month due to intestinal bleeding. Despite a negative outcome, this case seems to indicate a promising role for voriconazole in the treatment of S. apiospermum infections.

HIV-1 infection and the developing nervous system: lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors.

Neurologic abnormalities are common in HIV-1 infected patients and often represent the dominant clinical manifestation of pediatric AIDS. Although the neurological dysfunction has been directly related to CNS invasion by HIV-1, the pathogenesis of neurologic disorders remains unclear. Microglia and macrophages are major HIV-1 targets in the brain, whereas HIV-1 infected neurons or glial cells have been rarely reported. This suggests that indirect mechanisms may account for the severe neuronal damage observed in these patients. Nevertheless, immature, mitotically active neuronal and glial cells, which are present during fetal development, are susceptible to HIV-1 infection and replication in vitro, suggesting that HIV-1 infection during organ development may present unique features. To better characterize virus-host cells interactions in the developing CNS, we have examined the susceptibility of embryologically and biochemically distinct neuronal cell lines to HIV-1 infection. Here we show that mitotically active, immature neurons of distinct lineages, have different susceptibilities to HIV-1 infection and replication and different abilities to support viral gene expression. Mutational analysis of HIV-1 LTR reveals that a region of the viral promoter between nucleotide -255 to -166 is responsible for most quantitative and qualitative differences in viral transactivation among different neuroblasts. This suggests that specific regions of the viral promoter and cellular factors, either lineage- or differentiation-dependent, which bind to those regions, may contribute to control the levels of virus replication and possibly restrict the viral tropism in the developing brain. This may contribute to the establishment of a virus reservoir in the immature CNS and participate by either direct or indirect mechanisms to the severity of the AIDS-related pediatric neurological dysfunction.