Growth factors and IL-17 in hereditary angioedema.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder, due to C1-inhibitor deficiency, which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways which are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis in basal and crisis state and n = 19 healthy subjects. The samples were tested for IL-17, FGFb, G-CSF and GM-CSF, using Bio-plex kit. Data analysis was performed via nonparametric Spearman's correlations and two sets of linear mixed models. When comparing HAE subjects during basal and crisis states, we found out significantly (i.e., p value <0.05) higher values in crisis states rather than in basal states for the three growth factors and cytokine IL-17. When comparing healthy subjects versus HAE patients at basal state, we found out significantly higher values in HAE subjects only for GM-CSF, FGFb and IL-17, but not for G-CSF. In HAE patients, there is a connection between IL-17 and growth factors. The low-grade inflammation in absence of attacks is demonstrated by constant higher amount of IL-17, FGFb and GM-CSF with respect to healthy patients. This could indicate that in this disease there is a level of activation that maintains the system in a "tick-over state," that can be activate by several stimuli that are able to induce a increase in inflammatory mediators during the acute attack.

Modelling the non-linear multiple-lag effects of ambient temperature on mortality in Santiago and Palermo: a constrained segmented distributed lag approach.

OBJECTIVES: Exposure to ambient temperature can affect mortality levels for days or weeks following exposure, making modelling such effects in regression analysis of daily time-series data complex. METHODS: We propose a new approach involving a multi-lag segmented approximation to account for the non-linear effect of temperature and the use of two different penalized spline bases to model the distributed lag of both heat and cold exposure. Compared with standard splines, the novel penalized framework is more flexible at short lags where change in coefficients is greatest, and selection of the maximum lag appears substantially less important in determining the overall pattern of the effect. RESULTS: Applying the approach to daily mortality in Santiago (Chile) and Palermo (Italy), we observed a heat effect that was mostly immediate and followed by negative estimates consistent with short-term mortality displacement (harvesting). Cold effects were mostly positively sustained and more evenly distributed across the 60-day analysis period: in Santiago we estimated an overall increase in deaths of 2.36% (95% CI 0.26% to 4.51%) in the 65+ age group associated with every 1 degrees C decrease below the cold threshold, and an increase of 1.11% (0.09% to 2.14%) per 1 degrees C for Palermo. Heat effects for Palermo were much larger than for Santiago, and less harvesting of heat deaths was evident. The estimated heat thresholds were higher in Palermo than in Santiago. CONCLUSIONS: Our approach provides a flexible and precise method to quantify health effects of both heat and cold exposure at individual lags and to model the overall pattern of the delayed effect.

[Environmental pollution and short-term effects on human health in industrialized urban areas]. / Inquinamento ambientale ed effetti a breve termine sulla salute umana in aree urbane industrializzate.

Several studies investigating the adverse short-term effects of air pollution indicate that even concentrations of air pollutants close to or lower than air quality standards could negatively affect respiratory and cardiovascular health. Therefore, it seems crucial to develop knowledge about health adverse effects in industrialized urban areas. A time-series study on the association between air pollution levels and daily mortality and hospital admissions for respiratory and cardiovascular diseases is currently carried out in the town of Taranto, "area at high environmental risk" according to WHO because of the presence of several heavy industries and elevated rates for all-causes and all cancer mortality, higher than regional mortality rates, especially for lung cancer.

Parenteral iron supplementation for the treatment of iron deficiency anemia in children.

Iron-deficiency anemia impairs growth and intellectual development in children, which can be reversed only by early diagnosis and iron supplementation. Oral supplementation can efficiently replace stores, but in many cases parenteral iron is needed. Unfortunately some adverse reactions have limited its use in children. We compared the efficacy and safety of intramuscular and intravenous administration in 33 evaluable children with severe iron deficiency and/or iron-deficiency anemia who failed to respond to oral iron supplementation. Nineteen children received intravenous infusion and 14 intramuscular injections. All children showed recovery from iron-deficiency anemia, with statistically similar improvement in hemoglobin levels. The duration of treatment was longer in those receiving intramuscular injection. Parenteral iron therapy for the treatment of iron-deficiency anemia is a rapid, easy, and definitive solution to a long-troubling situation. We suggest the use of parenteral iron, in particular intravenous iron, in children who do not recover from severe iron-deficiency anemia after oral therapy. We should consider the physical and neuropsychological sequelae of long-lasting iron deficiency in children and the fact that oral supplementation is less likely to replace iron stores.

Impairment of nasal mucociliary clearance after radiotherapy for childhood head cancer.

BACKGROUND: Radiotherapy of the head region in children is known to cause long-term sequelae, such as facial, dental, and ocular abnormalities. We investigated whether a decreased nasal mucociliary function occurs after radiotherapy of the head in children. METHODS: A saccharin/charcoal test was performed in 20 children treated with radiotherapy of the head and in 20 controls, age-matched and gender-matched. RESULTS: We found a decreased nasal mucociliary clearance (lower percentage of responses (p = 0083) and longer mucociliary transport times (p =.0001) in the patients compared with the controls. The radiotherapy dosage influenced the response to the test (p =.0046). CONCLUSIONS: Irradiation of the head in children may cause impairment of mucociliary function, even permanently, which may predispose children to upper respiratory infections. We would suggest careful monitoring of such patients to detect as early as possible the clinical effects of the functional changes and to prevent the evolution to chronic diseases.

Ear involvement in childhood Langerhans' cell histiocytosis.

BACKGROUND: Ear involvement (EI) in Langerhans' cell histiocytosis (LCH) occurs quite often. We reviewed the Italian pediatric population of 251 children with LCH diagnosed between 1982 and 1995, focusing on EI, to highlight the prevalence, the clinical presentation, the outcome during follow-up, and the prognostic impact of otologic LCH. METHODS: EI was defined by chronic otorrhea and/or mastoid infiltration, external auditory meatus lesions, and middle/internal EI. The age at diagnosis, sex, system involved, organ dysfunction, treatment, disease control, and outcome were recorded. RESULTS: EI was noted at presentation in 34 children (13. 5%). They had a younger age at diagnosis (p=.0013) and near totality of multisystem disease (93.8% of patients with EI). Among patients with multisystem disease, children with EI seemed to have a higher risk of poor response and a higher percentage of second line treatment (p=.003). CONCLUSIONS: EI seems to identify patients with a particular disease behavior, which requires a more accurate evaluation at diagnosis, staging and treatment, and a strict follow-up, considering the possibility of an unfavorable outcome.

Polyclonal hypergammaglobulinemia at the onset of acute myeloid leukemia in children.

Polyclonal hypergammaglobulinemia (PHG) associated with hematological malignancies is a rare occurrence. We reviewed our series of 47 children with AML in order to define the prevalence of PHG and its prognostic value in achieving complete remission (CR) after induction treatment. Patients were stratified by immunoglobulin levels into two groups: with PHG and without PHG. CR reached after induction chemotherapy was considered a positive response. Conditional exact tests were used for the statistical analysis; conditional maximum likelihood estimates of the odds ratio (OR) were obtained. Significance levels (p) were determined from two-tailed tests. Twenty-two of 38 (57.9%) evaluable children showed PHG. Children with PHG and AML were more likely to be in CR after first induction treatment (OR=6.25, p=0.021), independent of sex, age at diagnosis, white blood cell count, percentage of blasts in the bone marrow, FAB phenotype, and treatment protocol. Infections seemed to positively influence early treatment response (p=0.038). PHG and infections were not statistically associated (p=0.16). PHG may result from the uncontrolled stimulation of B lymphocytes by cytokines. Infections or transfusions may act as triggers for the immune system, leading to the antileukemic effect seen in patients with AML and PHG going into spontaneous remission. It could be that this activation caused the larger number of CRs observed in our series. Clarification of why PHG exerts a positive influence on children with AML could help us to understand the ways by which the organism is able to control a malignant disease.