Omalizumab treatment in Samter's triad: case series and review of the literature.

OBJECTIVE: Samter's triad is the combination of asthma, aspirin sensitization, and nasal polyposis. Few data are available on the use of omalizumab in this disease. The study aimed to describe the impact of omalizumab on clinical and functional parameters and the quality of life of a series of patients with Samter's triad. Moreover, we aimed to provide a review of the literature on this topic. PATIENTS AND METHODS: We retrospectively described four patients with Samter's triad undergoing omalizumab therapy. Clinical, functional, and immunological data of these patients were collected at baseline and follow-up. RESULTS: Reduction of asthma exacerbations and salbutamol rescue therapy were observed in all patients after anti-IgE treatment together with an improvement in the quality of life. A significant improvement in FEV1, FVC, and FEF25-75 was observed. No major side-effects were observed. A total of 14 studies regarding omalizumab in aspirin-exacerbated respiratory diseases were included in the review, comprising 78 patients. All studies reported a good efficacy in improving asthma control; restoration of aspirin tolerance was repeatedly reported. CONCLUSIONS: The results of our case series and review of the literature suggest that omalizumab effectively improves asthma control, lung function tests, and quality of life in patients with Samter's triad.

Evaluation of Cardiovascular Toxicity Associated with Treatments Containing Proteasome Inhibitors in Multiple Myeloma Therapy.

INTRODUCTION: Recently new treatment options have substantially increased survival for patients with relapsed and/or refractory multiple myeloma (RRMM). Among these, proteasome inhibitors (PI), such as bortezomib and carfilzomib, offer high response rate and prolonged survival. These agents are generally well tolerated but demonstrated a significant cardiovascular toxicity, mostly for regimen containing carfilzomib. AIM: To assess the cardiovascular damage in patients treated with PI for RRMM. METHODS: 28 consecutive subjects treated with PI for RRMM were evaluated and compared with a population of 22 control (Con) subjects, matched for age, sex and mean 24 h blood pressure (24hMBP). All individuals underwent trans-thoracic echocardiography, ambulatory blood pressure monitoring and pulse wave velocity (PVW) study. RESULTS: PI patients did not have significant differences in blood pressure load and PWV compared to controls. Among echocardiographic parameters, the global longitudinal strain (GLS) was significantly decreased in PI subjects (p = 0.02). The GLS was significantly lower also considering only patients treated with carfilzomib. Moreover, among carfilzomib patients, we found increase values of left ventricle mass indexed by BSA (LVMi; p = 0.047). After correction for age, sex, BSA, 24hMBP and morphological and functional parameters of LV, treatment with PI and carfilzomib were significantly associated with GLS (p = 0.01; p = 0.036, respectively). CONCLUSIONS: PI treatment is associated with subclinical LV dysfunction in patients with RRMM compared to controls, as demonstrated by lower GLS values. These results are confirmed also considering patients treated with carfilzomib. Moreover, in this subgroup of patients, the LVMi is also increased, suggesting higher cardiotoxicity with this treatment.

Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis.

In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m2 and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.

A GRAS-like gene of sunflower (Helianthus annuus L.) alters the gibberellin content and axillary meristem outgrowth in transgenic Arabidopsis plants.

The GRAS proteins belong to a plant transcriptional regulator family that function in the regulation of plant growth and development. Despite their important roles, in sunflower only one GRAS gene (HaDella1) with the DELLA domain has been reported. Here, we provide a functional characterisation of a GRAS-like gene from Helianthus annuus (Ha-GRASL) lacking the DELLA motif. The Ha-GRASL gene contains an intronless open reading frame of 1,743 bp encoding 580 amino acids. Conserved motifs in the GRAS domain are detected, including VHIID, PFYRE, SAW and two LHR motifs. Within the VHII motif, the P-H-N-D-Q-L residues are entirely maintained. Phylogenetic analysis reveals that Ha-GRASL belongs to the SCARECROW LIKE4/7 (SCL4/7) subfamily of the GRAS consensus tree. Accumulation of Ha-GRASL mRNA at the adaxial boundaries from P6/P7 leaf primordia suggests a role of Ha-GRASL in the initiation of median and basal axillary meristems (AMs) of sunflower. When Ha-GRASL is over-expressed in Arabidopsis wild-type plants, the number of lateral bolts increases differently from untransformed plants. However, Ha-GRASL slightly affects the lateral suppressor (las-4-) mutation. Therefore, we hypothesise that Ha-GRASL and LAS are not functionally equivalent. The over-expression of Ha-GRASL reduces metabolic flow of gibberellins (GAs) in Arabidopsis and this modification could be relevant in AM development. Phylogenetic analysis includes LAS and SCL4/7 in the same major clade, suggesting a more recent separation of these genes with respect to other GRAS members. We propose that some features of their ancestor, as well as AM initiation and outgrowth, are partially retained in both LAS and SCL4/7.

[Dog population and dog breeds in Switzerland from 1955 to 2008]. / Hundepopulation und Hunderassen in der Schweiz von 1955 bis 2008.

Aim of this study is to present a survey of the dog population and breed distribution in Switzerland from 1955 to 2008 as basis to realize a population based canine cancer register for Switzerland. The number of dogs rose from 309'000 in 1955 to approximately 500'000 in 2008 correlating with a parallel increase of human population. The ratio of dogs per 100 inhabitants remains stable. This ratio is lower in German speaking compared to French or Italian speaking Cantons. The variety and popularity of breeds changed from 1955 to 2008, "winners" are Labrador and Golden Retrievers, Yorkshire and Jack Russel Terriers. Less popular breeds over the years are German Sheherd dogs and Poodles.

Ectopic expression of LEAFY COTYLEDON1-LIKE gene and localized auxin accumulation mark embryogenic competence in epiphyllous plants of Helianthus annuus x H. tuberosus.

BACKGROUND AND AIMS: The clone EMB-2 of the interspecific hybrid Helianthus annuus x H. tuberosus provides an interesting system to study molecular and physiological aspects of somatic embryogenesis. Namely, in addition to non-epiphyllous (NEP) leaves that expand normally, EMB-2 produces epiphyllous (EP) leaves bearing embryos on the adaxial surface. This clone was used to investigate if the ectopic expression of H. annuus LEAFY COTYLEDON1-LIKE (Ha-L1L) gene and auxin activity are correlated with the establishment of embryogenic competence. METHODS: Ha-L1L expression was evaluated by semi-quantitative RT-PCR and in situ hybridization. The endogenous level and spatial distribution of free indole-3-acetic acid (IAA) were estimated by a capillary gas chromatography-mass spectrometry-selected ion monitoring method and an immuno-cytochemical approach. KEY RESULTS: Ectopic expression of Ha-L1L was detected in specific cell domains of the adaxial epidermis of EP leaves prior to the development of ectopic embryos. Ha-L1L was expressed rapidly when NEP leaves were induced to regenerate somatic embryos by in vitro culture. Differences in auxin distribution pattern rather than in absolute level were observed between EP and A-2 leaves. More precisely, a strong IAA immuno-signal was detected in single cells or in small groups of cells along the epidermis of EP leaves and accompanied the early stages of embryo development. Changes in auxin level and distribution were observed in NEP leaves induced to regenerate by in vitro culture. Exogenous auxin treatments lightly influenced Ha-L1L transcript levels in spite of an enhancement of the regeneration frequency. CONCLUSIONS: In EP leaves, Ha-L1L activity marks the putative founder cells of ectopic embryos. Although the ectopic expression of Ha-L1L seems to be not directly mediated by auxin levels per se, it was demonstrated that localized Ha-L1L expression and IAA accumulation in leaf epidermis domains represent early events of somatic embryogenesis displayed by the epiphyllous EMB-2 clone.

Alpha-tryptophan synthase of Isatis tinctoria: gene cloning and expression.

Indole producing reaction is a crux in the regulation of metabolite flow through the pathways and the coordination of primary and secondary product biosynthesis in plants. Indole is yielded transiently from indole-3-glycerol phosphate and immediately condensed with serine to give tryptophan, by the enzyme tryptophan synthase (TS). There is evidence that plant TS, like the bacterial complex, functions as an alpha beta heteromer. In few species, e.g. maize, are known enzymes, related with the TS alpha-subunit (TSA), able to catalyse reaction producing indole, which is free to enter the secondary metabolite pathways. In this contest, we searched for TSA and TSA related genes in Isatis tinctoria, a species producing the natural blue dye indigo. The It-TSA cDNA and the full-length exons/introns genomic region were isolated. The phylogenetic analysis indicates that It-TSA is more closely related to Arabidopsis thaliana At-T14E10.210 TSA (95.7% identity at the amino acid level) with respect to A. thaliana At-T10P11.11 TSA1-like (63%), Zea mays indole-3-glycerol phosphate lyase (54%), Z. mays TSA (53%), and Z. mays indole synthase (50%). The It-TSA cDNA was also able to complement an Escherichia coli trpA mutant. To examine the involvement of It-TSA in the biosynthesis of secondary metabolism compounds, It-TSA expression was tested in seedling grown under different light conditions. Semi-quantitative RT-PCR showed an increase in the steady-state level of It-TSA mRNA, paralleled by an increase of indigo and its precursor isatan B. Our results appear to indicate an involvement for It-TSA in indigo precursor synthesis and/or tryptophan biosynthesis.

A thermal denaturation study of macronuclear chromatin in Blepharisma japonicum (Protozoa, Ciliophora, Heterotrichida).

The macronuclear chromatin of the ciliate Blepharisma japonicum, in two starvation states, was studied by thermal denaturation analysis. The behaviour of B. japonicum chromatin, native and reconstituted with Tetrahymena pyriformis H1 histone, was analysed. The data obtained are consistent with the hypothesis that B. japonicum macronuclear chromatin contains a H1-like peptide associated with the linker DNA, although this peptide is reduced in amount and/or chromatin stabilising ability when compared to Tetrahymena macronuclear H1.

H4 histone in the macronucleus of Blepharisma japonicum (Protozoa, Ciliophora, Heterotrichida).

Two clones, obtained by polymerase chain reaction from macronuclear DNA of the unicellular ciliated protist Blepharisma japonicum, were isolated and sequenced. They correspond to fragments of two different putative H4 histone genes. The existence of multiple H4 histone genes was also suggested by Southern blot hybridisation experiments employing one of the obtained clones as a probe. Two B. japonicum H4 protein fragments, which were directly sequenced, show differences in the amino acid sequences too. The comparison of the obtained B. japonicum H4 partial amino acid sequences with each other, and with H4 from other ciliates and from representative microbial and multicellular organisms, highlights the larger histone heterogeneity of lower eukaryotes compared to that observed in higher organisms.

Activation of the hemostatic process in patients with unruptured aortic aneurysm before and in the first week after surgical repair.

BACKGROUND AND OBJECTIVE: It has been previously suggested that activation of coagulation and fibrinolysis may sometime occur in patients with unruptured aortic aneurysm. However, the incidence of this complication and the effect of surgical repair are unknown. The objective of our study was to gain further information on this topic. METHODS: We investigated activation of the hemostatic process in 20 consecutive patients with unruptured abdominal aortic aneurysm. We then evaluated the effect of surgical repair of the vascular abnormalities. RESULTS: Both before and in the first week after surgery, the large majority of patients showed clear signs of activation of coagulation (increased plasma levels of prothrombin fragment 1 + 2 and fibrin peptide A), and many had low levels of the natural anticoagulant antithrombin III. Platelets were activated in all cases (high levels of plasma beta-thromboglobulin), and signs of platelet consumption (thrombocytopenia and/or increased mean platelet volume) were present in most of them. INTERPRETATION AND CONCLUSIONS: Activation of the hemostatic process occurs in nearly all patients with abdominal aortic aneurysm and could play a role in the hemorrhagic and thrombotic events that can complicate the clinical development of these subjects.

Carotid intima-media thickening and in vivo LDL oxidation in patients with essential hypertension.

Low density lipoproteins (LDL) from hypertensive patients are more prone to in vitro oxidation and undergo a more pronounced oxidation in vivo. Due to the pro-atherogenic activity of oxidatively modified LDL, the correlation between the carotid intima-media thickening (IMT) and the markers of in vivo LDL oxidation was investigated in hypertensive patients. A cross-sectional study on 101 normocholesterolemic patients with newly diagnosed and untreated essential hypertension was performed. The occurrence of in vivo LDL oxidation was evaluated by measuring the titers of autoantibodies against Cu(2+)-oxidised LDL (oxLDL) and malondialdehyde-derivatised LDL (MDA-LDL). The extent and degree of atherosclerosis and the IMT were measured by means of carotid and femoral ultrasonography with a duplex scanner equipped with a high resolution probe. We did not find significant correlations between in vivo LDL oxidation parameters and the extent of atherosclerotic lesion in the entire group of hypertensive patients. However, a significant direct correlation was detected between the carotid IMT and the titer of autoantibodies against both oxLDL and MDA-LDL in hypertensive patients without advanced atherosclerotic plaques. The results obtained support the hypothesis that enhanced LDL oxidation may be one of the pathophysiological events related to the formation and progression of early atherosclerotic lesions (IMT) in carotid arteries of hypertensive patients.

[Radiosurgical excision in the treatment of cervical intraepithelial neoplasia]. / La radiochirurgia escissionale (REP) nel trattamento della neoplasia cervicale intraepiteliale.

39 patients affected by CIN had undergone radio surgical excision. This non-traumatic method employs 3.8 MHz radio waves are employed to cut and/or coagulate. The radio surgical excision was carried out by a loop electrode, or microneedle, according to the colposcopic, histologic and microcolpohysteroscopic characteristics of the cervical lesion. In fact 14 patients, among whom 11 affected by CIN I and 4 by CIN II with a total visibility of squamous columnar junction and not extended lesion of the cervical canal, had undergone radio surgical excision through various dimensions loop according to the size of the tissue to be excised. Whereas 10 CIN II patients who had not entirely visible squamous columnar junction or large cervical canal lesion, and 14 CIN III patients underwent to radiosurgical conization through a subtle and extensible tungsten thread according to the size of the tissue to be excised. In the 100% of the both groups the recovery was confirmed after three and six months. Inno cases cervical canal stenosis was observed and the squamous columnar junction resulted well visible. In both groups no thermal damages on the excised tissue, which could create difficulties on the histological diagnosis, were observed. Therefore, this method resulted an easy and cheap technique to be executed in surgery with excellent results under the therapeutic and economical aspect.

A case of congenital hypoplasia of the right external iliac artery.

A 18 years male had congenital hypoplasia of the right external iliac artery and thrombosis of its narrowest part. Congenital megacolon, anal atresia and hyposomical nanism were also present. Surgical intervention was indicated because he was developing arterial insufficiency and muscular hypotrophy of the right leg. A bypass was performed with a reversed autogenous vein between the common iliac artery and the common femoral artery.

5'-Methyl-cytosine in the macronuclear DNA of Blepharisma japonicum.

Brief report on the presence of 5'-methyl-cytosine as a minor base (0.56%) in the macronuclear DNA of the ciliate protozoan Blepharisma japonicum. The evidence comes from electrophoresis of macronuclear DNA digested by appropriate restriction endonucleases and high-performance liquid chromatography.

[Mitomycin C: current status of knowledge and use in laryngeal tumors]. / Mitomicina C: stato attuale delle conoscenze e suo impiego nei tumori laringei.

The Mitomycin are a family of antibiotics useful in the treatment of breast, lung, stomach, colorectal and other solid tumours. One member of the family, MC (Mitomycin C) is examined and the present biochemical, physiological, microbiological, pharmacological and clinical knowledge of the drug and its use in laryngeal tumours is reviewed.

Histones of human lung carcinoma and human lung tissue. Analysis by two-dimensional electrophoresis.

Histones prepared from human lung and human lung carcinoma were analyzed by a 2-dimensional electrophoresis method able to separate histone subfractions. The comparative analysis of electrophoretograms showed differences in the relative amounts of H1, H2A, and H3 histone subfractions extracted from human lung and human lung carcinoma chromatin.