PO-46 - Influence of extracellular vesicles derived from AML patients on stem cells and their microenvironment.

INTRODUCTION: Acute myeloid leukemia (AML) is characterized by rapid growth of leukemic blast cells. Extracellular vesicles (EVs) are shed from normal and pathologic cells and express membrane proteins and antigens, reflecting their cellular origin. AIM: To explore whether bone marrow EVs of AML patients originate from blast cells and are capable of influencing hematopoietic stem cells (HSC) in a pseudo-natural microenvironment obtained by co-culture of HSC with mesenchymal stem cells (MSC). MATERIALS AND METHODS: Bone marrow (BM) samples were collected from healthy controls and patients with newly diagnosed AML at three time points: diagnosis, nadir and remission. EV concentration, cell origin and expression of coagulation proteins were characterized by FACS. Stem cells were obtained from Ficoll gradient of cord blood (CB) followed by CD34+ isolation. Cord blood stem cells with or without MSC were co-incubated with AML EVs. EV internalization was demonstrated by FACS-AMNIS and confocal microscopy. Mir-125b and -155 expressions in the cells were analyzed by RT-PCR. RESULTS: AML patients were enrolled in the study. The total BM-EVs number was higher in patients at first remission compared to controls, while blast EV counts (labeled with anti-CD34, CD33, CD117) were higher in patients at diagnosis compared to controls and to patients in remission. Internalization of CD117+/CD33+ BM-EVs to cord blood stem cells in the presence or absence of MSC was evaluated by FACS-AMNIS. Confocal microscopy of CD33+ stained EVs strengthens the findings and shows presence of EVs even in the cytoplasm and the nucleus. Quantitative analysis of mir-125b and mir-155 expression in cord blood stem cells incubated with AML EVs revealed a clear tendency of increased expression in case of cell exposure to AML EVs in comparison to healthy control EVs. This tendency was emphasized in the presence of MSC. CONCLUSIONS: EVs of AML patients are generated from blast cells. By internalization into naïve stem cells they can influence their differentiation. Moreover, the presence of mesenchymal stem cells is likely to be essential to the process.

Is high prevalence of vitamin D deficiency evidence for asthma and allergy risks?

BACKGROUND: Studies suggest a link between vitamin D deficiency and development of asthma and allergic diseases. AIM: To determine a) the association between vitamin D and asthma among children, b) difference in level of vitamin D in asthmatic children and control, and c) effect of vitamin D on atopy markers. SETTING: Case-control study done, between October 2009 to July 2010, on asthmatics and controls (< 15 years) at Pediatric Allergy-Immunology Clinics and Primary Health care Clinics (PHC), Qatar. METHODS & SUBJECTS: A total of 483 cases and 483 controls matched by age, gender and ethnicity. Sociodemographic & clinical data was collected through physician diagnosis and questionnaire. Their health status was assessed by past or present clinical manifestations, family history, physical examination, BMI, and serum 25(OH) vitamin D, calcium, and phosphorus. RESULTS: 44.8% of asthmatic and 50.0% of controls were males, and 55.2% of asthmatic and 50% of controls were females. The mean age (+/- SD, in years)for asthmatic versus controls was 7.0 +/- 3.8 vs. 8.4 +/- 3.6. Vitamin D deficiency was more prevalent in asthmatics than controls. The mean value of Vitamin D in asthmatics was much lower than the normal value, and there was a significant difference found in the mean values of vitamin D between asthmatics (17.5 +/- 11.0) and the controls (20.8 +/- 10.0). Furthermore, there were statistically significant differences between asthmatic subjects and controls with respect to serum level of vitamin D (p < 0.001). Lower Vitamin D levels were associated with more allergic disease and elevated serum IgE. CONCLUSION: Serum vitamin D levels were lower in asthmatic than control. Vitamin D deficiency was higher among children with asthma, allergic rhinitis, atopic dermatitis, acute urticaria, and food allergy. In addition, vitamin D deficiency was associated with IgE atopy markers in asthmatic children more than controls.

Anticancer oncolytic activity of respiratory syncytial virus.

Oncolytic virotherapy is an emerging biotherapeutic platform for cancer treatment, which is based on selective infection/killing of cancer cells by viruses. Herein we identify the human respiratory syncytial virus (RSV) as an oncolytic virus. Using prostate cancer models, we show dramatic enhancement of RSV infectivity in vitro in the androgen-independent, highly metastatic PC-3 human prostate cancer cells compared to the non-tumorigenic RWPE-1 human prostate cells. The oncolytic efficiency of RSV was established in vivo using human prostate tumor xenografts in nude mice. Intratumoral and intraperitoneal injections of RSV led to a significant regression of prostate tumors. Furthermore, enhanced viral burden in PC-3 cells led to selective destruction of PC-3 cancer cells in vitro and in xenograft tumors in vivo due to apoptosis triggered by the downregulation of nuclear factor-kappaB (NF-kappaB) activity (and the resulting loss of anti-apoptotic function of NF-kappaB) in RSV-infected PC-3 cells. The intrinsic (mitochondrial) pathway constitutes the major apoptotic pathway; however, the death-receptor-dependent extrinsic pathway, mediated by the paracrine/autocrine action of tumor necrosis factor-alpha produced from infected cells, also partly contributed to apoptosis. Thus, the oncolytic property of RSV can potentially be exploited to develop targeted therapeutics for the clinical management of prostate tumors.

The impact of air pollution on hospital admission for respiratory and cardiovascular diseases in an oil and gas-rich country.

OBJECTIVES: Aim of this study was to evaluate the impact of air pollution on hospital admissions for respiratory and cardiovascular diseases in an oil rich developing country, State of Qatar. METHODS: A prospective cohort population based study was conducted at different stations of Qatar during the period (2002-2005) for recording the concentration of air pollutants daily for sulphur dioxide (SO2), nitric oxide (NO), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3) and particulate matter (PM10). Hospital admission data were collected from the inpatient discharge database of the Medical Records Department, Hamad General Hospital. RESULTS: An average of 5.36 admissions from ischemic heart diseases was counted daily in all the population which was even higher than the respiratory diseases (3.4/day). Minimum temperature was inversely correlated with all pollutants except for O3 and SO2. CONCLUSION: There was an association between increasing air pollutant levels and patients admitted for respiratory and cardiovascular diseases.

Optimization study of the femtosecond laser-induced forward-transfer process with thin aluminum films.

The parameters for an effective laser-induced forward-transfer (LIFT) process of aluminum thin films using a femtosecond laser are studied. Deposited feature size as a function of laser fluence, donor film thickness, quality of focus, and the pulse duration are varied, providing a metric of the most desirable conditions for femtosecond LIFT with thin aluminum films.

Montelukast treatment in children with moderately severe atopic dermatitis.

BACKGROUND: Moderately severe atopic dermatitis makes up nearly one-fifth of children with atopic dermatitis. OBJECTIVE: To determine the clinical and laboratory effects of montelukast in moderately severe atopic dermatitis. METHODS: Randomized, double-blind, placebo-controlled, crossover trial with washout period, conducted from May 2002 to February 2006. The study involved 25 patients, 2-16 years old with dermatitis. Patients received oral montelukast (9 patients, Group B) or placebo (16 patients, Group A) in phase 1, and were crossed over to placebo or montelukast, respectively, for phase 2. Patients included if > 10% of skin was involved and failed response to 2 week conventional treatment. Itching, sleep disturbance, frequency of use of oral antihistamines & topical steroids, severity scores were serially assessed. In addition, eosinophil and serum IgE were serially collected. RESULTS: Most of patients were 6-10 years of age. Both groups had comparable gender distribution. The patients in Group B were more likely to have a history of bronchial asthma (55.6%) or allergic rhinitis (33.3%) than patients in Group A, but were less likely to have a positive history of atopy. While on montelukast, there was a reduction of mean score for itching in phase 2, for sleep disturbance in phase 2, for antihistamines in phase 1, for extent-of-disease in phase 1 and 2, and for severity score in phase 2 and blood eosinophil & IgE in phase 2. CONCLUSION: Montelukast reduces itching, sleep disturbance, disease extent and severity, blood eosinophil count and serum IgE.

Role of breast feeding in primary prevention of asthma and allergic diseases in a traditional society.

BACKGROUND: The fact that breastfeeding may protect against allergic diseases remains controversial, with hardly any reports from developing countries. Prolonged breastfeeding was shown to reduce the risk of allergic and respiratory diseases. AIM: The aim of this study was to assess the relationship between breastfeeding and the development of childhood asthma and allergic diseases in Qatari children at age 0-5 years. Additionally, this study investigated the effect of prolonged breastfeeding on the allergic diseases in a developing country. DESIGN: This is a cross sectional survey. SETTING: Well baby clinics and Pediatric clinics in the 11 Primary Health Care Centers and Hamad General Hospital, Hamad Medical Corporation, State of Qatar. SUBJECTS: A multistage sampling design was used and a representative sample of 1500 Qatari infants and pre-school children with age range of 0-5 years and mothers aged between 18 to 47 years were surveyed during the period from October 2006 to September 2007 in Qatar. Out of the 1500 mothers of children, 1278 mothers agreed to participate in this study with the response rate of 85.2%. METHODS: A confidential, anonymous questionnaire was completed by the selected subjects assessing breastfeeding and allergic diseases. Questionnaires were administered to women who were attending Primary Health Centers for child immunization. Questionnaire included allergic rhinitis, wheezing, eczema, and additional questions included mode and duration of breastfeeding, tobacco smoke exposure, number of siblings, family income, level of maternal education, parental history of allergies. Univariate and multivariate statistical methods were performed for statistical analysis. RESULTS: More than half of the infants (59.3%) were exclusively breastfed, followed by infants with partial breastfeeding (28.3%) and artificial fed (12.4%). There was a significant difference found across these three categories of infants in terms of their age groups, smoking status of father, socio-economic status and parental consanguinity. Asthma (15.6%), wheezing (12.7%), allergic rhinitis (22.6%), and eczema (19.4%) were less frequent in exclusive breast fed children, compared to infants with partial breast feeding and formula milk. Ear infection (P = 0.0001) and eczema (P = 0.007) were found significant in infants with the history of maternal atopy, while asthma (P = 0.0001) and allergic rhinitis (P = 0.015) were found significant in infants with the history of paternal atopy. The main factors associated with mode of feeding were mothers having first baby, asthmatic mother and parental history of allergic rhinitis. The risk of allergic diseases, eczema, wheeze and ear infection in particular, were lower in children with prolonged breast feeding (>6 months) than in those with short-term breast feeding duration (<6 months). CONCLUSION: The current study indicates that exclusive breast-feeding prevents development of allergic diseases in children. The main factors associated with breastfeeding for allergic diseases were being the first baby, maternal history of asthma, and parental history of allergic rhinitis. The study findings opens a big avenue for interventional role of breastfeeding. Therefore, we recommend breastfeeding is as one possible way to reduce the risk of onset asthma and allergic diseases in developing countries.

Does hospitalization for asthma and allergic diseases occur more frequently in Ramadan fasting: a population based study (2000-2004).

OBJECTIVE: Over one billion Muslims fast worldwide during the month of Ramadan. Fasting during Ramadan is a radical change in life style for the period of a lunar month. Our objective in this study was to investigate whether Ramadan fasting has any effect on the incidence of asthma and to assess whether Ramadan Fasting affected normal lung function values. DESIGN: This is a hospital-based cohort study. SETTING: Hamad General Hospital, Hamad Medical Corporation, Doha, State of Qatar. PATIENTS: We prospectively reviewed 1590 asthmatic Muslim patients who were hospitalized with asthma over a four year period from January 2000 to December 2004. Patients were divided according to the time of presentation in relation to the month of Ramadan, one month before, during and one month after Ramadan. METHODS: Pulmonary function tests were performed on an electronic spirometer (Compact Vitalograph, Buckingham, U.K.). Performance of the spirometric test and data collection were according to as described by the American Thoracic Society. RESULTS: There were 1590 patients studied. Among them, 901 were males (56.7%) and 689 were females (43.3%). Their mean age was 30 years (15-60). All patients expressed clinical allergy, 454 patients (28.6%) had asthma and rhinitis, 513 patients (32.3%) had allergic rhinitis, 300 patients (18.9%) had asthma alone and 10.6% had other allergic conditions. The ventilatory capacity of lung function parameters mean did not show any statistically significant differences between a period of pre-Ramadan, during Ramadan and after Ramadan concerning FVC, FEV1, FEF(25-75) FEV1/FVC, and PEF values. CONCLUSION: This study demonstrated that no significant difference was found in number of hospitalization and the mean spirometric values for asthma while fasting during the month of Ramadan when compared to the non-fasting months.

Development of a femtosecond micromachining workstation by use of spectral interferometry.

A workstation that permits real-time measurement of ablation depth while micromachining with femtosecond laser pulses is demonstrated. This method incorporates the unamplified pulse train that is available in a chirped-pulse amplification system as the probe in an arrangement that uses spectral interferometry to measure the ablation depth while cutting with the amplified pulse in thin metal films.

Pet ownership: its effect on allergy and respiratory symptoms.

BACKGROUND: Studies have shown that pets are very important sensitizing agents in patients with asthma. Respiratory disorders such as asthma and allergic rhinitis are common in the State of Qatar. OBJECTIVE: The aim of the present study was to determine whether exposure to pets and domestic animals plays a significant role in the development of asthma and allergic rhinitis among Qatari population. DESIGN: A hospital-based prospective descriptive study conducted. SETTING: Allergy Laboratory at the Hamad General Hospital and Hamad Medical Corporation, State of Qatar. PATIENTS: Adult patients over 12 years of age diagnosed with bronchial asthma and/or allergic rhintis who were referred for allergy skin prick test. 1106 adult patients recruited with respiratory diseases of suspected allergic origin who attended Allergy Clinic at the Hamad General Hospital, during three years from January 2001 to April 2003. Total of 1106 whom 607 were females (54.9 %) and 499 were males (45.1%) and their mean was age 30 years (12-48). METHODS: Skin Prick Test (SPT) was performed on 1106 patients for common allergens whom the blood sample was taken for measuring total IgE concentration. RESULTS: There were 1106 patients studied and 496 patients (44.9%) had positive and 610 (55.1%) had negative skin prick tests. Out of 1106 patients, 311 patients (28.1%) had asthma; 503 patients had allergic rhinitis (45.5%) and 87 patients (7.8%) had skin allerg. Three hundred and forty (340/1106=30.7%) of the 1006 subjects studied had at least one animal at home, and the remaining 69.3% had never had pets in the home. A further 12% reported having had pets in the past, but not anymore. Cats (26.7%), goats (15%) and birds (14.7%), animals were the most common present within the house and was the most frequently seen pet types when compared to other pet types. The risk of having asthma (RR: 1.29; 95% CI: 1.07-1.55; p=0.008), allergic rhinitis (RR: 1.48; 95% CI: 1.24-1.77; p<0.0001) and eczema (RR: 3.56; 95% CI:1.24-1.77; p<0.0001) was significantly higher in subjects with animals than in patients without. CONCLUSION: In the present study, the prevalence of asthma, rhinitis, and skin allergy was significantly more common in families with animals than in those without.

[Mite allergy in the domestic horse: experience of an equine veterinarian specializing in the field of allergy]. / Allergie aux acariens chez le cheval domestique: experiénce d'un vétérinaire équin spécialisé dans le domaine de l'allergie.

When medical history and clinical examination for a recurrent or chronic cough reveal the presence of perennial allergy, the practitioner would be advised to look for mites present in the horse's environment. He can propose this service to his clients.

[Recurrent or chronic urticaria in thoroughbred race-horses: clinical observations]. / Urticaire récidivante ou chronique chez le pur-sang à l'entraînement: constatations cliniques.

Recurrent or chronic urticaria seems to be a food allergy in thoroughbred race-horses during the training season. In resistant cases, allergologic techniques will be required to determine aetiology. Intradermal skin tests with fresh allergenic food may cause syndromic reaction as urticaria and akin to enteritis in some horses. In most cases, an elimination of the allergen responsible brings a rapid and long-lasting result. Study about 22 cases.

[Importance of recombinant k82 in the diagnosis of latex allergy]. / Intérêt du k82 recombi dans le diagnostic de l'allergie au latex.

Measurement of IgEs keeps a predominant place in the diagnosis of allergy and in particular in certain pathologies such as those induced by dangerous allergens like, for example, latex. The contribution of recombinant allergens is a significant element in the measurement of IgEs and we have observed this for latex. Sensitivity of recombinant k82 is significantly greater than that of k82. It permits better detection of patients who are sensitised to latex and thus a better prevention by absence of frequent contact with latex gloves and detergents.

Early cardiotoxicity of the CHOP regimen in aggressive non-Hodgkin's lymphoma.

BACKGROUND: To determine the incidence of early cardiotoxicity induced by the CHOP regimen in patients with aggressive non-Hodgkin's lymphoma (NHL) and to identify associated risk factors. PATIENTS AND METHODS: A retrospective analysis included 135 consecutive patients who had been treated with the CHOP (cyclophosphamide, doxorubicin, vincristin, prednisone) regimen as first-line therapy between 1994 and 2000. The cardiac evaluation was based on a determination of the resting left ventricular ejection function (LVEF) by gated blood-pool imaging. Cardiotoxicity was defined as a significant decrease in LVEF or clinical evidence of congestive heart failure (CHF). RESULTS: Twenty-seven (20%) patients developed a cardiac event within 1 year of treatment. Among these, 14 patients had clinical signs of CHF. Three patients died suddenly from presumed cardiac causes. In multivariate analysis, a cumulative dose of doxorubicin >200 mg/m(2) [odds ratio (OR) = 4.2, P = 0.005)] and age over 50 years (OR = 2.9, P = 0.03) appeared to be significant risk factors. CONCLUSION: Early clinical and subclinical cardiotoxicity was frequent in patients receiving the CHOP regimen. The threshold of the cumulative dose of doxorubicin appeared to be low: at doses >200 mg/m(2), 27% of patients had cardiac events. Elderly patients appeared to be at higher risk. The development of cardioprotective strategies or alternative treatments are mandatory for aggressive NHL patients.

[Seafood allergy]. / Allergie alimentaire aux fruits de mer.

Products of the sea are important source of food. Increase in consumption, due to their nutritive value has also led to a great frequency of reactions, including those that are immunologically mediated. Although hypersensitivity reactions to sea products are often easy to identify and can be confirmed by specific in vitro and in vivo tests, some patients can only be diagnosed by double-blind provocation test against placebo (DBPCFC). An atypical or incomplete clinical history suggests, always, contamination with toxins and/or parasites such as Anisakis. Crossed reactivity between different sea products is frequent. However, there are clinical differences between allergy to molluscs, crustaceans and fishes. From precise evaluation of the reactions to sea produce, will result a reduced and reasoned suppression from this type of allergens at food levels.

[Value of quantitative IgE measurement]. / Intérêt du dosage quantitatif de l'IgE.

The results of assay of IgE can only be expressed by a very imprecise system of classes. Quantification of the measurement of IgE by the method of the CAP-system of prognosis of allergic patients. Expression of IgE by a measurement of intensity of fluorescence allows the establishment of a decent curve for each allergen. It makes a method of predictive evaluation of risk of the allergy pathology for each allergen. It significantly improves the sensitivity, since it allows detection of IgE at levels less than 0.35 KUA/l. Thus it gives a considerable improvement for the clinician at the level of diagnosis avoiding the "gold standard" provocation test in allergy diagnosis as well at the level of prognosis.

[The place of new antihistamines in allergy management. Apropos of desloratadine]. / Place des nouveaux antihistaminiques dans la prise en charge de l'allergie: à propos de la desloratadine.

Desloratadine, the active metabolite of loratadine, is a new antihistamine. Because of its anti allergy properties, desloratidine has an affinity for histamine receptors 25 to 100 times greater to those of the usual antihistamines, coupled with a capacity to inhibit the production of pro-inflammatory mediators. When evaluated in healthy volunteers, the half life of desloratadine has been estimated at 27 hours, which is comparable with a night time length of action. Many clinical studies made with patients suffering with allergic rhinitis or chronic idiopathic urticaria have shown a rapid symptom reduction, lasting 24 hours after first taking. This action was correlated with an improvement in socio-professional activity, sleep and quality of life in general. In patients suffering from allergic rhinitis, rhinomanometry showed a significant improvement in nasal congestion by desloratadine. The clinical advantages of desloratadine on antihistamines taken previously were measured in a study made on almost 48,000 patients, of whom 91% found its efficacity satisfactory. By its powerful action, coupled with an excellent tolerance profile, desloratadine represents a real therapeutic advance for allergic patients.

Use of dobutamine stress echocardiography in detecting silent myocardial ischaemia in asymptomatic diabetic patients: a comparison with thallium scintigraphy and exercise testing.

AIMS: Silent myocardial ischaemia is frequent in diabetic patients. The aim of this study was to compare the efficacy of thallium-201 single-photon emission computed tomography (201Tl SPECT) coupled with exercise stress testing (EST), and dobutamine stress echocardiography (DSE) in the detection of asymptomatic coronary artery disease. METHODS: Fifty-six asymptomatic diabetic patients, with a known duration of diabetes > 15 years for Type 1 and > 5 years for Type 2, having at least three added risk factors, but without rest ECG abnormalities, were enrolled in this prospective study. All of them were submitted to DSE with a maximum infusion rate of 40 microg/kg per min dobutamine +/- i.v. atropine, and to 201Tl SPECT coupled with EST. Coronary angiography was performed if at least one test was abnormal. RESULTS: Diabetic patients were 37 males and 19 females, aged mean (sd) 60 +/- 10 years, 10 Type 1 and 46 Type 2, with a known duration of disease of mean (sd) 17 +/- 9 years. Feasibility of DSE was 91%. No serious complication occurred during the test. Coronary angiography was performed in 26 patients (47%); 17 were abnormal (30% of the whole group): six patients had a one-vessel, six a two-vessel and five a three-vessel disease. Predictive positive value was 69% for DSE, 75% for 201Tl SPECT and 60% for EST. DSE was falsely negative in four cases vs. eight for 201Tl SPECT and nine for EST. CONCLUSIONS: Asymptomatic coronary disease is common in diabetes associated with other risk factors. DSE appears useful in its detection and a good alternative to 201Tl SPECT.

[Fatal anaphylaxis after eating wild boar meat in a patient with pork-cat syndrome]. / Anaphylaxie mortelle après ingestion de sanglier chez un patient porteur du syndrome porc-chat.

Crossed allergy between pork and cat epithelia was described by us in 1994. It is due to serum albumin. Nowadays, other bio-chemical observations allow "completion" of the syndrome by extension of the crossed reactivity between other mammal meats and other epithelia of dog and horse. The authors report an observation of the pork-cat syndrome (developing in the form of anaphylaxis, and then ending in the death of the patient), following consumption of wild boar meat. Co-factors, such as effort, taking alcohol or hormonal condition may complicate the picture to make diagnosis more difficult.

[Biological diagnosis in allergy and immunology]. / Le diagnostic biologique en immuno-allergologie.

Diagnosis in allergy-immunology is based on clinical elements (History--Skin tests) and biological elements: search for IgE to allergens or for allergens that are presumed to be responsible and in the case of asthma or rhinitis on tests of respiratory function and/or rhinomanometry and/or nasofibroscopy; finally on provocation tests if necessary.