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Rhinitis and asthma are often associated and the two disorders interact at various levels. Rhinitis typically precedes the development of asthma and can contribute to unsatisfactory asthma control. The presence and type of asthma is influenced by sensitization, and the duration and severity of allergic rhinitis. Nasal symptoms, airflow and markers of inflammation directly correlate with lower airway involvement. Local tissue factors, such as microbial stimuli and systemic inflammatory mechanisms, play a role in the clinical expression of the allergic airway syndrome. There is increasing evidence that suggests a major involvement of airway epithelial cells in the pathogenesis of both asthma and allergic rhinitis. Even in patients with rhinitis who do not have asthma, subclinical changes in the lower airways and inflammatory mediators can be detected. The pathogenic role of paranasal sinus infections in respiratory allergy has been better elucidated but there remains a need for further research. Treatment of established rhinitis may affect asthma control and could have some impact on airway obstruction, but a direct effect of rhinitis therapy on lower airway inflammation remains to be clearly established.

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe.

The aim of this Global Allergy and Asthma European Network (GA(2)LEN) consensus report is to provide recommendations for patient-reported outcomes (PROs) evaluation in clinical trials for allergic diseases, which constitute a global health problem in terms of physical, psychological economic and social impact. During the last 40 years, PROs have gained large consideration and use in the scientific community, to gain a better understanding of patients' subjective assessment with respect to elements concerning their health condition. They include all health-related reports coming from the patient, without involvement or interpretation by physician or others. PROs assessment should be performed by validated tools (disease-specific tools when available or generic ones) selected taking into account the aim of the study, the expected intervention effects and the determinant and confounding factors or patient-related factors which could influence PROs. Moreover, each tool should be used exclusively in the patient population following the authors' indications without modification and performing a cross-cultural validation if the tool must be used in a language that differs from the original. The result analysis also suggests that the relevance of PROs results in any interventional study should include a pre-post assessment providing information concerning statistical differences within or among groups, rates of response for the PROs and a minimal important difference for the population. The report underlines the importance of further investigation on some topics, such as the quality assessment of existing PROs tools, the definition of inclusion and exclusion criteria and a more extensive evaluation of the correlation between PROs, besides health-related quality of life, and clinical data.

Background: Quality of life (QOL) is an important issue in allergic rhinitis and has been evaluated in a number of studies that have shown how it is impaired in untreated patients and improved by effective treatment. However, there are no data concerning QOL after sublingual immunotherapy (SLIT) in polysensitized patients., Objective: To evaluate the effect, in real-life clinical practice, of SLIT on QOL in a population of polysensitized patients with allergic rhinitis., Methods: We prospectively evaluated 167 consecutively enrolled polysensitized patients with allergic rhinitis. QOL was measured in all cases with the Rhinoconjunctivitis Quality of Life Questionnaire at baseline and after 1 year of SLIT (performed in approximately 70% of cases using single allergen extracts provided by the same manufacturer)., Results: The most frequent causes of sensitization were grass pollen, Parietaria, and house dust mites. The mean number of sensitizations per patient was 3.65. SLIT was performed with 1 extract in 123 patients (73.6%), with 2 extracts in 31 patients (18.6%), and with more than 2 extracts in 13 patients (7.8%). The mean values of all the QOL items improved significantly (P < .01 in all cases), with the following reductions noted: activities, 3.96 to 2.89; sleep, 2.07 to 1.56; general problems, 2.16 to 1.5; practical problems, 3.69 to 2.58; nasal symptoms, 3.57 to 2.50; eye symptoms, 2.92 to 1.83; and emotional aspects, 2.2 to 1.44., Conclusions: This study provides evidence that QOL can be improved in polysensitized patients treated with SLIT, and that the use of just 1 or 2 allergen extracts seems to be sufficient and effective in terms of improving QOL.

Purpose of Review: The main feature of allergen-specific immunotherapy is its capacity to modify the natural history of the disease, reducing the development of asthma and new sensitizations after 3-4 years of treatment. For this reason, adherence to the therapy is mandatory, as happens for all chronic medical treatment., Recent Findings: Though subcutaneous immunotherapy is administered directly by physicians, the rate of adherence is surprisingly low, at less than 70%. The explanations for a poor subcutaneous immunotherapy adherence include inconvenience, lack of efficacy, costs and loss of working hours.Local nasal immunotherapy has a very low adherence rate (27%), due to the local nasal side effects.For sublingual immunotherapy, data are available from clinical trials and postmarketing surveys, which are favourable overall (rates of compliance >75%). Cost was the most common reason for discontinuation, followed by inconvenience, feeling of inefficacy and side effects., Summary: Studies addressing the adherence to allergen-specific immunotherapy in literature are lacking. In real life, costs and patient education are crucial issues in conditioning adherence to this treatment. Reduction of costs and more efforts in education of patients and also specialists may improve the adherence to immunotherapy.

Background: Subcutaneous immunotherapy is effective for the treatment of respiratory allergy, and it is largely used in Italy, but no systematic safety assessment has been carried out so far., Objective: To assess prospectively the safety of injection immunotherapy in a multicentre, real-life survey., Methods: Eleven Italian allergy departments recorded the clinical characteristics of systemic reactions (SRs) due to immunotherapy. Vaccines were prescribed according to guidelines; only standardized depot extracts were used. SRs were graded according to the EAACI recommendations, and were classified as immediate or delayed., Results: One thousand seven hundred and thirty-eight patients (847 males, age range 5-71) received immunotherapy from eight different manufacturers, for a total of 2038 courses (300 patients received two extracts). A total of 60 785 injections were given over a mean immunotherapy duration of 3 years. Overall, 95 reactions were observed in 57 patients (3.28%), corresponding to 4.7% of the courses and 1.56/1000 injections. Twenty-five patients experienced more than one adverse event. There were 34 grade 2, 60 grade 3 and one grade 4 reactions and no fatality. SRs occurred more frequently in patients with asthma than in patients with rhinitis alone (4.1% vs. 1.1%), and were equally distributed between the build-up and the maintenance phase. Ragweed and grass extracts caused significantly more side effects than other allergens., Conclusion: In this large prospective study, the rate of SRs was low, thus confirming that injection immunotherapy has an acceptable risk/benefit ratio when prescribed and carried out according to recommendations.

Polysensitization is very common in allergic patients and was previously reported to be associated with more severe symptoms and impaired quality of life. Polysensitization is often considered as a contraindication for specific immunotherapy (SIT). This study is aimed at evaluating the allergist attitude for decision making in choosing SIT in a cohort of Italian polysensitized patients. Moreover, the 1-year effectiveness of the prescribed sublingual immunotherapy (SLIT) in this cohort was evaluated. The study was performed on 244 patients (109 males, 135 females, mean age 28.7 years, S.D. 12.0) with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA criteria) treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, type of diagnosis, severity of symptoms, use of drugs, and adverse events were evaluated at baseline and after 1 year. A total of 230 patients were treated with SLIT: 165 with a single extract, and 65 with two different extracts (mix). SLIT treatment significantly improved disease staging, and reduced symptom severity and drug use. No systemic reaction was reported. In conclusion, these findings provide preliminary evidence that SIT is effective and safe in polysensitized patients after 1 year of treatment also using single extracts, and thus does not represent an obstacle for prescribing SIT.

Background: The goal of asthma therapy is to achieve an optimal level of disease control, but the relationship between asthma control, impact of comorbid rhinitis and health related quality of life (HRQoL) in real life remains unexplored., Objective: The aims of this real life study were to evaluate asthma control, the impact of asthma (with and without rhinitis) on HRQoL, the relationship between asthma control and HRQoL, and the role of rhinitis on asthma control and HRQoL., Methods: 122 asthma patients completed the Asthma Control Test, Rhinitis Symptoms score (T5SS) and RHINASTHMA., Results: Asthma control was unsatisfactory (44.27% of uncontrolled patients), as well as HRQoL. Controlled patients controlled showed significantly lower scores in all the RHINASTHMA domains compared to uncontrolled. Irrespective of their level of control, patients with rhinitis symptoms showed worse HRQoL in Upper Airways (UA) (P < 0.0001), Lower Airways (LA) (P < 0.001), and Global Summary (GS) (P < 0.0001). In patients with symptomatic rhinitis, RHINASTHMA were lower in controlled asthma patients (UA P = 0.002; LA P < 0.0001; RAI P < 0.01; GS P < 0.0001). Asthma control was associated with lower T5SS score (P = 0.034)., Conclusion: Asthma control in real life is unsatisfactory. Rhinitis and asthma influence each other in terms of control and HRQoL. The control of rhinitis in asthma patients can lead to an optimization of HRQoL related to the upper airways, while this phenomenon is not so evident in asthma. These results suggest to strengthen the ARIA recommendation that asthma patients must be evaluated for rhinitis and vice versa.

Background: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients., Methods: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated., Results: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations., Conclusions: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Background: Allergen immunotherapy (IT) is an effective treatment of respiratory allergy, but requires strict rules of performance. This makes compliance particularly relevant, but thus far only a few studies have investigated this issue., Methods: We reviewed all the available articles on compliance and adherence with IT in its different forms of administration, ie, subcutaneous (SCIT), sublingual (SLIT), and local nasal (LNIT)., Results: Early studies, when only SCIT was available, reported a low compliance, ranging from 45% to 60%, but the demanding schedules used, with very frequent injections, accounted for this outcome, as shown by patients' recognition of inconvenience as the major cause of noncompliance. The most recent studies reported a good compliance, estimated in 75% to 90%, to both SCIT and SLIT, inconvenience remaining the major cause of noncompliance, followed by cost of the treatment. The only study addressing LNIT found a very poor compliance (27%), the major cause being the side effects, with repeated nasal reactions to the allergen extract., Conclusions: Adequate education of patients and optimization of administration schedules, with fine balancing between dose effectiveness and cost, are the factors most likely to achieve further improvement of compliance with IT.

Compliance is a major determinant for allergy treatment, especially in children. Sublingual immunotherapy (SLIT) is self-managed at home, and no quantitative data on pediatric adherence are available. We studied the compliance in a large real-life setting. A simplified schedule of SLIT was used, consisting of a 10-day updosing phase followed by maintenance treatment in monodose containers to be taken daily (SLITOne). Italian specialists throughout Italy assessed the compliance in children who were newly prescribed SLIT according to guidelines. Parents were contacted with unscheduled telephone interviews at the third and sixth month of therapy and asked to count at that moment the remaining vials. Data from 71 children (38 boys, age range 2-13 yr) were enclosed in the database. Thirty had rhinoconjunctivitis, four asthma and 37 rhinoconjunctivitis + asthma. SLIT was prescribed for: mites in 57 (81%) subjects, grasses in 11 (15%) and 3 (4%) grass + olive mixture. Compliance data were available for all children at 3 months, and for 56 at 6 months. At 3 months, 85% of subjects had a compliance rate >75% (69% of them adhered >90%). At 6 months, 84% had a compliance rate >75% (66% of them adhered >90%). In four cases SLIT was discontinued for economical reasons, and in one case (1.4%) for side effects probably related to therapy. These data obtained in a quite large sample of children and in real-life confirm that the compliance with SLITOne is good, despite the therapy managed at home.

Background: Aeroallergens and the environment play an important role in the pathogenesis of respiratory allergies. In a 12-year study carried out in Northern Italy (geographic area of Parma), the effects of airborne pollen and meteorological conditions on the incidence of allergic asthma and rhinoconjunctivitis were evaluated., Patients and Methods: Among 9,060 subjects examined for respiratory pathologies at our Allergy Unit, Parma Hospital, Italy, from 1992 to 2003, only 1,054 positive to only one type of inhalant allergen in the skin prick test were studied, to avoid bias of cross-reactivity. Allergy and clinical aspects were compared with the duration of the pollination period, and peaks and total concentrations of airborne pollen., Results: Our data showed a significantly growing trend of allergy to mites, pets and birch pollen and a significant increase in asthma, and a significantly decreasing trend of positive reactions to grasses and a decrease in rhinoconjunctivitis. At the same time, there was a significant decrease in total pollen counts, concentration peaks and pollination period of grasses. A significant increase was only observed in ragweed and ash-olive total and peak pollen concentrations., Conclusions: Significant correlations between the increasing incidence in asthma and allergy to mites, pets and birch pollen are shown. The decrease in the total pollen count and concentration peaks of grass pollen was correlated to the decreasing trend of rhinoconjunctivitis. The trend of increasing concentrations of ash-olive and ragweed pollen was not accompanied by an increase in the related allergy., (Copyright 2007 S. Karger AG, Basel.)

Hymenoptera stings may be responsible for both local and systemic reactions; these can be immediate or delayed, depending on the time between the sting and the development of signs or symptoms. Delayed clinical reactions have been reported, although unusual, due to serum sickness and/or affecting organs or systems generally not involved in the immediate reaction, such as heart, kidneys, central and peripheral nervous systems. This paper describes the clinical and immunological findings in a 51-year-old subject, who, after two stings of paper wasps, the second one after the third venom immunotherapy (VIT) injection, presented immediate large local and systemic allergic reactions which quickly improved after e.v. methylprednisolone administration. About 40 hours later, he developed acute polyradiculoneuropathy with muscle weakness, paresthesia, difficulties in standing up and walking. Skin tests and specific IgE determination showed allergy to paper wasp. The activation, by wasp venom, of peripheral blood mononuclear cells in primary culture, evaluated by tritiated thymidine incorporation proliferation assay, showed an important hypersensitivity to wasp venom. Therefore our results suggest the hypothesis that the polyradiculoneuritis causative etiopathogenetic mechanism might be a delayed immunological response to wasp antigens followed by an allergy-triggered autoimmune reaction, as previously suggested by other authors; they found lymphocytic infiltrates in demyelinization areas and at perivascular levels, by histologic examination of autoptical and bioptical material of patients with nervous system lesions after hymenoptera stings.

Background: The overall effect of fruit and vegetable intake on urinary stone risk profile is not yet known., Methods: We studied the effect of a two-week period of fruit and vegetable elimination on urinary stone risk profile in 12 normal adults, and of supplementing the diet with a fair quantity of low-oxalate fruits and vegetables in 26 idiopathic calcium stone formers characterized by hypocitraturia and a very low fruit and vegetable intake in their usual diet., Results: In the normal subjects, the elimination of fruits and vegetables from the diet decreased the urinary excretion of potassium (-62%), magnesium (-26%), citrate (-44%) and oxalate (-31%), and increased that of calcium (+49%) and ammonium (+12%) (P < 0.05 for all). The relative saturation for calcium oxalate and calcium phosphate increased from 6.33 to 8.24 (P = 0.028), and from 0.68 to 1.58 (P = 0.050), respectively. In the hypocitraturic stone formers, the introduction of these foods in the diet increased urinary volume (+64%), pH (from 5.84 to 6.19), excretion of potassium (+68%), magnesium (+23%), and citrate (+68%), while it decreased the excretion of ammonium (-18%) (P < 0.05 for all). The relative saturation for calcium oxalate and uric acid fell from 10.17 to 4.96 (P < 0.001), and from 2.78 to 1.12 (P = 0.003), respectively., Conclusion: The total elimination of fruits and vegetables in normal subjects brings about adverse changes in the urinary stone risk profile that are only partially counterbalanced by a reduction in oxalate. In contrast, the addition of these foods to the diet of hypocitraturic stone formers not used to eating them not only significantly increases citrate excretion without affecting oxalate excretion, but also decreases calcium oxalate and uric acid relative saturation.

We analyzed, in a middle-sized hospital, the problems related to the so-called "difficult discharges", conceived as situations involving an economic, human and organizational burden exceeding patients' and their families' capacities and requiring a specific involvement of territorial services. During a whole year (July 1, 2001-June 30, 2002) the cases found were 591. We demonstrated that the problem concerns mainly elderly patients, almost equally distributed between males and females, a quarter of the sample being represented by patients who had recently undergone surgery and whose discharge difficulties were mostly related to mixed social and sanitary problems. This kind of patients is faced with long-term hospitalization implicating a large number of intra-hospital transfers due to the presence of severe and disabling pathologies, mainly neoplasms and strokes, often associated with other serious diseases, various complications and difficult situations from the health point of view. About half of the patients had the possibility to go back home, while the rest required lodging in territorial structures such as nursing homes and retirement homes. The average time-lapse between the possible discharge indicated by the hospital physician and the actual discharge was 10 days, with global annual 6106 days of "improper" hospitalization. Our conclusion is that the phenomenon of difficult discharges is nowadays a very topical problem and that it should be faced with a new model of continuous and integrated assistance organization.

The cardiovascular system is frequently affected in systemic lupus erythematosus (SLE). The observation of clinical manifestations related to the presence of coronary artery disease has not been frequently documented in young SLE patients. In these patients, the presence of inflammatory or thrombotic vascular lesions is often documented by anatomo-histological studies in the absence of previous clinical manifestations. The purpose of this study was to evaluate the presence of myocardial perfusion defects in SLE patients. The study was carried out in 15 patients without clinical signs of myocardial ischemia, 1 male and 14 females, 24 to 64 years old, with a mean SLE duration of 10.2 +/- 7.5 years. All the patients had normal blood pressure; electrocardiogram and Doppler-echocardiographic analysis showed values in the normal range. All the patients underwent thallium-201 exercise stress imaging repeated 3 hours later at rest, with tomographic SPECT analysis. Exercise test was carried out until submaximal load, without induction of ST segment alterations or symptoms. Scintigraphic scan showed normal thallium-201 SPECT imaging in 11/15 patients, while the other 4 patients had a slight perfusion defect, 3 of them in the inferior segment, in 2 non reversible and in 1 reversible; 1 patient had a non reversible defect in the septal segment. These slight perfusion defects, prevalently non reversible, may sometimes be a false positive imaging. Our results are in contrast with the literature observations concerning the frequent incidence of thallium-201 perfusion defects in SLE patients. In young asymptomatic SLE patients, our study does not report very important data indicating myocardial ischemia and suggesting the presence of significant coronary obstruction or vasculitis.

Nutrition plays a major role in the pathogenesis of the most widespread forms of nephrolithiasis, i.e. calcium (calcium oxalate and phosphate) and uric acid stone disease. For this reason, dietary measures are the first level of intervention in primary prevention, as well as in secondary prevention of recurrences. An unbalanced diet or particular sensitivity to various foods in stone formers can lead to urinary alterations such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and an excessively acid urinary pH. Over the course of time, these conditions contribute to the formation or recurrence of kidney stones, due to the effect they exert on the lithogenous salt profile. The fundamental aspects of the nutritional approach to the treatment of idiopathic nephrolithiasis are body weight, diet and water intake. This paper will present data resulting from our own investigations and the most significant evidence in literature., (Copyright 2004 S. Karger AG, Basel)

MAP kinase/ERK kinase (MEK)-extracellular signal-regulated kinase (ERK) kinases are frequently activated in acute myelogenous leukemia (AML), and can have prosurvival function. The purpose of this study was to induce downmodulation of MEK-ERK activation in AML primary blasts in order to detect the effect on cell cycle progression and on the apoptosis of leukemic cells. We investigated 14 cases of AML with high ERK 1/2 activity and four cases with undetectable or very low activity. After 24 h incubation of the AML blasts with high ERK activity using PD98059 (New England BioLabs, Beverly, MA, USA), a selective inhibitor of MEK1 phosphorylation, at concentrations of 20 and 40 microM, we observed a strong decrease in the levels of ERK1/2 activity. A significant decrease of blast cell proliferation compared with untreated controls was found. In contrast, the proliferation of blast cells that expressed low or undetectable levels of ERK activity was not inhibited. Time-course analysis demonstrated that the downmodulation of MEK1/2, ERK1 and ERK2 dual-phosphorylation was evident even after 3 h of treatment with 20 and 40 microM. The cleavage of poly(ADP-ribose) polymerase (PARP), an early sign of apoptosis, appeared after 18 h of PD98059 treatment at concentrations of 20 and 40 microM in eight of the 14 cases. After 24 h of treatment, cleaved PARP appeared in all 14 cases. Time-course analysis of cell cycle progression and apoptosis showed that PD98059 induced a G1-phase accumulation with low or undetectable levels of apoptosis after 24 h incubation; after 48 and 72 h incubation, a significant increase of apoptosis was observed. Thus, the primary effect of ERK downmodulation was a cell cycle arrest followed by the apoptosis of a significant percentage of the leukemic blasts. The preclinical model of leukemia treatment reported in this paper makes further comment with regard to MEK1 inhibition as a useful antileukemic target, and encourages the conducting of in vivo studies and clinical investigations.

Introduction: The expression, activity and functions of mitogen-activated protein (MAP) kinases in primary human hematopoietic progenitors (HP) have not yet been fully clarified., Material and Methods: To perform our experiments we used a stroma-free cell culture system in which the combination of FLT3 ligand (FL), stem cell factor (SCF) and thrombopoietin (TPO) induces massive expansion and proliferation of cord blood HP. The addition of IL-3 results in a rapid decrease of HP due to the prevalence of maturation and cell death. To detect extracellular regulated kinase (ERK) immunoenzymatic activity we recovered HP from FL, SCF and TPO stimulated long term cultures (LTC) after four weeks of culture. Some samples were recovered 16 h after addition of IL-3 to the LTC. We selectively immunoprecipitated p44/42 ERK kinase from 245 microg of cell lysates. We then analysed dual-phosphorylation of ERK-activating kinase-kinase (p45 MEK1/2) and of p44 ERK1 and p42 ERK2, and investigated MEK and ERK expression., Results: ERK activity, MEK1, and p42 and p44 ERK dual-phosphorylation were undetectable in the expanding, greatly proliferating and self-renewing HP. However, after addition of IL-3 sustained (still detectable 16 h after the stimulus) and high levels of ERK activity and dual-phosphorylation of the kinases were seen. The levels of MEK and ERK expression were stable in the different phases., Conclusions: These findings add new information on the intracellular mechanisms of HP and help explain the very low levels of hematopoietic toxicity recently seen when treating cancer with down-modulators of ERK activity.

Introduction: We report the results of a study investigating signaling proteins in 26 cases of primary acute myelogenous leukemia. We studied the Shc adaptor proteins p52/p46Shc, which can activate the RAS/Mitogen Activated Protein kinase pathway, p66Shc which is uncoupled from RAS/MAP kinases and the MAP kinase family members Extracellular signal Regulated Kinase (ERK) and c-Jun NH2-terminal protein Kinase (JNK) or Stress Activated Protein Kinase (SAPK)., Material and Methods: CD34+ and CD34- fractions of four human normal bone marrow and unfractionated bone marrow samples were investigated. Immunoblottings, immunoenzymatic and in vitro assays were performed., Results: Shc protein isoforms were constitutively expressed in all the AML cases examined. Tyrosine-phosphorylation of p53/p46Shc isoforms were found in CD34+ but not in the majority of CD34- cases. p66Shc isoform was not tyrosine-phosphorylated in CD34-, and was tyrosine-phosphorylated only in some CD34+ cases. Expression and activation of ERK was constitutively present in the majority of AML patients analysed. JNK/SAPK was expressed but not activated in the AMLs examined. Activation occurred after treatment of the leukemic cells by anisomycin, etoposide, and cytarabine. ERK and JNK/SAPK activation were not detectable in the hematopoietic precursors of human normal bone-marrow., Conclusion: These data bear implications for the role of Shc-MAP kinase pathway in normal hemopoiesis and AML leukemogenesis.

This study was aimed at investigating abnormalities in left ventricular size and function in patients with systemic lupus erythematosus without overt cardiovascular manifestations, in order to detect a very early impairment in myocardial function. Seventeen females and 1 male with systemic lupus erythematosus of 4 to 20 year duration and without clinical evidence of heart disease were studied. Twelve healthy volunteers, matched for age, sex and quatelet index, were utilized as controls. Each patient had a two-dimensional M-mode echocardiographic and Doppler examination. In patients with systemic lupus erythematosus there was an increase in left ventricular ejection fraction (p < 0.001), a slight reduction of end-diastolic volume index and a significant decrease of end-systolic volume index (p < 0.001). In the same patients we also found prolongation of the isovolumic relaxation time (p < 0.02), a clear impairment of diastolic filling parameters. Peak E velocity was lower (p < 0.01), peak A velocity was higher (p < 0.01), with a clear lowering, of the corresponding E/A ratio (p < 0.001) in patients with systemic lupus erythematosus.

We present the clinical case of a 26-year-old woman, suffering systemic lupus erythematosus for 15 years, who suddenly had coronary heart disease with angina pectoris on mild effort. Thallium 201 exercise test demonstrated clearcut anteroseptal and apical perfusion defects, whereas repeated echocardiography showed a hypokinetic anteroseptal segment; ECG also reported new Q wave in lead V4. After stronger corticosteroid and immunosuppressive treatment, angina pectoris attenuated and perfusion defects disappeared within few months. We hypothesize a coronary artery vasculitis in the course of systemic lupus erythematosus, probably associated with early coronary artery atherosclerosis.