Omalizumab decreases exacerbation frequency, oral intake of corticosteroids and peripheral blood eosinophils in atopic patients with uncontrolled asthma.

Omalizumab is a humanized monoclonal anti-IgE antibody approved in 2005 by the European Medicine Agency (EMA) for the treatment of severe persistent allergic asthma, which remains inadequately controlled despite optimal therapy with high doses of inhaled corticosteroids and long-acting ß2-adrenergic agonists. Within this context, the present observational study refers to 16 patients currently treated with omalizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy, whose anti- IgE therapy was started in the period included between March 2007 and February 2010, thus lasting at least 10 months. After 40 weeks of add-on treatment with omalizumab, very relevant decreases were detected, in comparison with pre-treatment mean (± standard deviation) values, in monthly exacerbation numbers (from 1.1 ± 0.6 to 0.2 ± 0.4; p < 0.01) and oral corticosteroid consumption (from 22.6 ± 5.0 to 1.2 ± 2.9 mg/day of prednisone; p < 0.01). These changes were associated with stable improvements in lung function, expressed as increases of both FEV1 (from 53.6 ± 14.6% to 77.0 ± 14.9% of predicted values; p < 0.01) and FEV1/FVC ratio (from 56.3 ± 9.5% to 65.8 ± 9.2%; p < 0.01). Moreover, in 5 patients who persistently had increased numbers of eosinophils (mean ± SD: 15.9 ± 8.0% of total WBC count; absolute number: 1,588.0 ± 956.9/µl) despite a long-lasting therapy with inhaled and systemic corticosteroids, the peripheral counts of these cells decreased down to near normal levels (mean ± SD: 6.3 ± 2.3% of total WBC count; absolute number: 462.0 ± 262.3/µl) after 16 weeks of treatment with omalizumab. Therefore, this descriptive evaluation confirms the efficacy of add-on omalizumab therapy in selected patients with exacerbation-prone, chronic allergic uncontrolled asthma, requiring a continuous intake of oral corticosteroids.

Estrogen receptor polymorphisms and the risk of endometrial cancer.

OBJECTIVE: There is evidence that estrogens and some of their metabolites are involved in endometrial cancer pathogenesis. As estrogens mediate their effects via the estrogen receptors, ESR1 and ESR2, the objective of this investigation was to determine whether six single nucleotide polymorphisms (SNPs) in these two genes were over-represented in a population of endometrial cancer patients compared with a healthy matched control population, thereby associating differences in these genes with endometrial cancer. DESIGN: The study is a case-control investigation large enough to detect a two-fold increased risk, assuming a dominant genetic model, with P = 0.05 and 80% power. SETTING: The study and control populations were all from the Hunter-New England region of New South Wales, Australia collected between the years 1992 and 2005. POPULATION: The study consisted of 191 endometrial cancer patients and 291 healthy controls matched for gender and age. METHODS: Two SNPs in ESR1 and four SNPs in ESR2 were genotyped using PCR-based restriction fragment length polymorphism analysis and real-time PCR. Odds ratios were calculated using unconditional logistic regression and SIMHAP was used for haplotype analysis, adjusting for potential endometrial cancer risk factors. Kaplan-Meier survival analysis, Cox regression and t tests were used to examine the patient's age of diagnosis of endometrial cancer and genotype. MAIN OUTCOME MEASURES: Over-representation of ESR1 and ESR2 polymorphisms in the endometrial cancer population compared with the control population indicates an involvement in the development and/or progression of disease. RESULTS: Two ESR1 (rs2234693 and rs9340799) and two ESR2 (rs1255998 and rs944050) polymorphisms were associated with an increased risk of endometrial cancer. Following adjustment for risk factors, the association with the ESR1 and ESR2 polymorphisms (rs2234693, rs1255998 and rs944050) remained highly significant. Haplotype analysis revealed that carriers of the ESR1 haplotype (variant alleles; rs2234693 and rs9340799) and the ESR2 haplotype (variant allele; rs1255998 and wild-type alleles; rs944050, rs4986938 and rs1256049) were at an increased risk (OR 1.862, P = 0.013 and OR 1.918, P = 0.046 respectively). This risk was even greater in women carrying both risk haplotypes (OR 5.041, P = 0.007). CONCLUSIONS: Our data suggest that the ESR1 (rs2234693 and rs9340799) and the ESR2 (rs1255998 and rs944050) polymorphisms may be associated with an increased risk of developing endometrial cancer.

[Occupational exposure to hexavalent chromium during aircraft painting]. / Esposizione occupazionale a cromo esavalente nelle operazioni di verniciatura degli aeromobili.

Hygienists are interested in hexavalent chromium due to its genotoxic and carcinogenic effect on humans. The use of products containing hexavalent chromium is decreasing in many industrial fields because of the substitution with less-toxic compounds. In the aeronautical industry, however, the chromate are added to primer paint as a corrosion inhibitor of aircrafts surfaces: so hexavalent chromium compounds are available in many primers with a composition ranging from 10% to 13%. The application of these primers by using electrostatic guns potentially exposes painting and coating workers at high concentrations of aerosols containing Cr(VI). The aim of the present study is the evaluation of professional exposure to hexavalent chromium during aircraft painting, by adopting both environmental personal sampling and biological monitoring. To valuate workers exposure levels the personal measurements results have been compared with the exposure limit values (TLV-TWA) and the urinary chromium contents with the biological exposure indices (IBE). Moreover the strategy of coupling environmental sampling with biological monitoring seems to be a useful instrument to measure the validity of the individual protection devices.

Pelvic anatomy and MRI.

An in-depth knowledge of the anatomy of the pelvis and pelvic sidewall is necessary before a gynaecologist can even contemplate making an initial examination and start management in cases of pelvic pathology or malignancy. This chapter provides basic information on gross pelvic anatomy structures that are of clinical relevance and discusses their correlation with medical imaging, especially magnetic resonance imaging (MRI). MRI is an ideal non-invasive technique in the assessment of normal anatomy and tissue characterization of pelvic pathology. The excellent soft-tissue contrast and the ability to direct multiplanar imaging and to demonstrate blood vessels without the use of intravenous contrast make MRI superior to other imaging modalities in the evaluation of pelvic abnormalities. The anatomical relation of the visceral organs, the differential zonal anatomy of the corpus uteri and the cyclical endometrial changes during the menstrual cycle are well depicted with MRI.

[Chemical risk of exposure to volatile organic compounds in the field of restoration of art objects]. / Il rischio chimico di esposizione a composti organici volatili nel settore del restauro di oggetti d'arte.

The use of chemicals during restoration practices involves emissions of toxics depending on both the amount of original products used and the specific techniques applied. Restorers perform a great variety of techniques by using not standardized operative procedures: moreover, they are exposed to mixtures and very rarely to single chemicals. In this study we evaluated workers' exposure to solvent mixture which were generated during restoration of archaeological metal handcraft. Exposure to low levels of twelve organic compounds has been experimented inside a public restoration laboratory: based on the data presented in this article we assume that inside restoration workplaces a diffused indoor contamination can take place. The indoor pollution can generate a risk of an uncontrolled exposure to volatile mixtures: therefore the emissions of solvents during restoration practices has to be avoided even if they cause a low level of exposure.

Intraperitoneal interferon-alpha-2b for patients with no macroscopic disease following second-look laparotomy.

Low to intermediate doses of interferon-alpha-2b (10-30 million units every 2 weeks for six cycles), were administered intraperitoneally to 14 patients with no macroscopic disease at the completion of second-look laparotomy. Eight patients had a negative second-look so the treatment was given as consolidation therapy. Five patients had a microscopically positive second-look and one patient had small macroscopic disease completely resected. Toxicity was low. However, four of the eight patients with a negative second-look relapsed (two in the peritoneum) and five of the other six patients have also relapsed, all in the peritoneum. Four of these latter six patients received intraperitoneal cisplatinum in addition to the interferon. Mean time to relapse for the group with a negative second-look was 18 months, while it was 16 months for the group with microscopic residual disease. Median follow-up was 38 months. Intraperitoneal interferon in the dosages given in this trial does not seem to be effective as consolidation therapy, nor is it effective for patients with microscopic residual disease at second-look laparotomy.

The equivalents of human blood and spleen dendritic cell subtypes can be generated in vitro from human CD34(+) stem cells in the presence of fms-like tyrosine kinase 3 ligand and thrombopoietin.

Dendritic cells (DCs) are immune cells specialized to capture, process and present antigen to T cells in order to initiate an appropriate adaptive immune response. The study of mouse DC has revealed a heterogeneous population of cells that differ in their development, surface phenotype and function. The study of human blood and spleen has shown the presence of two subsets of conventional DC including the CD1b/c(+) and CD141(+)CLEC9A(+) conventional DC (cDC) and a plasmacytoid DC (pDC) that is CD304(+)CD123(+). Studies on these subpopulations have revealed phenotypic and functional differences that are similar to those described in the mouse. In this study, the three DC subsets have been generated in vitro from human CD34(+) precursors in the presence of fms-like tyrosine kinase 3 ligand (Flt3L) and thrombopoietin (TPO). The DC subsets so generated, including the CD1b/c(+) and CLEC9A(+) cDCs and CD123(+) pDCs, were largely similar to their blood and spleen counterparts with respect to surface phenotype, toll-like receptor and transcription factor expression, capacity to stimulate T cells, cytokine secretion and cross-presentation of antigens. This system may be utilized to study aspects of DC development and function not possible in vivo.

General practitioners and management of patients with respiratory diseases in a real life survey.

AIM: The prevalence of respiratory diseases has been assessed in community based epidemiological studies. General practice is the ideal position to intercept chronic respiratory illness and manage the first level of follow up as well. Aim of this study was to obtain General Practitioners (GPs) data about management and clinical setting of patients with respiratory diseases. METHODS: This is a prospective observational study; 272 Italian GPs were involved and equally distributed on the Italian territory. The interviews were performed by means of a questionnaire consisting in which consisted of 25 questions regarding individual demographics, catchment area, professional behavior, health attitudes. RESULTS: Each GP reported that about 13% of the pooled patients had a respiratory disease. Concerning as for chronic respiratory illnesses, spirometry was frequently prescribed and in these patients 63% of the interviewed GPs thought that the lung functional test was fundamental. GPs also reported the importance of improving health education, well aware of its importance in the prevention of respiratory diseases; and furthermore in improving the current health system organization. As for with regard to cigarette smoke, interviewed GPs reported that the 26% of their assisted subjects were smokers and the commitment to discouraging the smoking habit was very high. CONCLUSION: This is a large National survey that involved GPs and real life data about management of patients with respiratory diseases. The role of GPs in the management of chronic respiratory patients represents an important tool valuable in increasing primary care identification, education and treatment of respiratory diseases.

Indacaterol for chronic obstructive pulmonary disease (COPD).

Indacaterol (Onbrez), previously known as QAB-149-AFA, is a novel ultra-long-acting beta2-adrenoceptor agonist that was recently approved by the European Commission as a new once-daily maintenance bronchodilator treatment of airflow obstruction in adult patients with chronic obstructive pulmonary disease (COPD). COPD is a major cause of chronic morbidity worldwide. According to World Health Organisation, it was the fifth cause of death in 2002 and it is projected to be the fourth cause of mortality by 2030. The rapid onset of action of indacaterol, duration of bronchodilation for at least 24 hours, and an optimal safety profile make this drug an interesting and attractive weapon for its use in fight against the COPD.

Mucocele of the appendix with magnetic resonance imaging findings.

Mucocele of the appendix is a rare lesion caused by abnormal accumulation of mucus. Although preoperative diagnosis is important to avoid rupture of a mucocele, the diagnosis is often made at surgery. We report a case of an appendiceal mucocele that mimicked a hydrosalpinx on CT and MRI.

Stage IV ovarian cancer: a retrospective study on patient's management and outcome in a single institution.

The management of stage IV epithelial ovarian carcinoma remains controversial. The aim of this study was to evaluate and compare our results to other published series. A retrospective database and casenote review was performed on all patients diagnosed with stage IV disease over a ten-year period (1992-2002). Survival analysis was performed using the Kaplan-Meier and Mantel-Haenszel methods. The study group comprised 23 women. Nine had positive pleural effusions (39.1%), and 14 had other sites of metastases (60.9%). Nine patients underwent interval debulking (39.1%), and 14 were operated on primarily (60.9%). We had six postoperative complications (26.1%) but no perioperative deaths. Optimal cytoreduction (inferior or equal to 2 cm residual disease) was obtained in 18 patients (78.3%). The overall median survival was 22.6 months. There was no statistically significant difference in overall or disease-free survival between primary surgery and interval debulking. Patients with positive pleural effusions had significantly reduced survival compared to those with distant metastases in other sites. Interestingly, there was no difference in survival between optimally and suboptimally cytoreduced patients. Debulking surgery can be performed in patients with stage IV ovarian cancer, with an acceptable level of morbidity. Optimal cytoreduction is achievable in the majority of these patients. Interval debulking should be considered in selected patients.

Stage 1 endometrial cancer: treatment modalities and factors influencing recurrence.

One hundred and nineteen patients treated for FIGO Stage 1 endometrial adenocarcinoma were reviewed retrospectively to determine if adjuvant radiotherapy reduced disease recurrence. The patients had all been treated in the Hunter Region of New South Wales over a 10-year period from 1978 to 1988. Median follow up was 82 months with a range of 24 to 163 months. Treatment consisted of surgery alone (75.6%), surgery and brachytherapy (17.6%), surgery and megavoltage therapy (4.2%), and surgery with both brachytherapy and megavoltage therapy (2.5%). The overall recurrence rate was 10.1%. Recurrence at the vaginal vault alone occurred in 3.4%. The median time to recurrence was 25.0 months. A statistically significant correlation was found between overall recurrence risk and poorly differentiated lesions (p < 0.0001). Just failing to reach statistical significance were age over 70 years (p < 0.06) and patient weight less than 70 kg (p = 0.06). Depth of myometrial invasion (p = 0.17), use of adjuvant radiotherapy (p = 0.17) and uterine cavity size (p = 0.48) were not significantly correlated with risk of recurrence. The 5-year survival rate was 93.8%.

Endometrial stromal sarcoma resembling adenomyosis and menstrual-phase endometrium.

BACKGROUND: Low-grade endometrial stromal sarcoma (LGESS) and endometriosis are two conditions of different prognostic significance that are usually not difficult to distinguish histologically. CASE: We present the case of a 38-year-old woman who underwent laparotomy after a diagnosis of endometrial stromal neoplasm on uterine curettings. Uterine enlargement and regional and paraaortic lymphadenopathy were found. Pathology showed adenomyotic-like myometrial hypertrophy and menstrual-like shedding of tumor in involved lymph nodes. The finding of large areas of endometrial stromal cells without accompanying glands forming tumorous masses in both sites supported the diagnosis of LGESS. We believe that this is the first time that these phenomena have been reported in LGESS. CONCLUSION: In these cases, adenomyotic myometrial hypertrophy and menstrual shedding have been used to distinguish endometriosis from LGESS, but do not appear to be absolute criteria. Endometriosis and LGESS are undoubtedly separate entities, but occasionally may resemble each other.

Clear-cell carcinoma of the ovary in a 19-year-old woman.

The risk of inadvertently treating an ovarian malignancy is always present regardless of the patient's age, clinical history, ultrasound features, serum tumour markers, menopausal status and intraoperative findings. This risk can be minimized by paying particular attention to high-risk characteristics in any of the above assessment criteria and by obtaining an intraoperative frozen section if there is any suspicion of malignancy. The same approach should be used whether the initial treatment is by laparotomy or laparoscopy. We present a case of clear-cell carcinoma of the ovary in a 19-year-old woman where there was delay in diagnosis and treatment as a result of an incorrect initial histopathology assessment. This appears to be the youngest patient reported in the literature with a clear-cell carcinoma of the ovary.

A systematic review of single-dose intramuscular methotrexate for the treatment of ectopic pregnancy.

The use of single-dose intramuscular methotrexate for the primary treatment of ectopic pregnancy is increasing in frequency in many countries. We performed a systematic review of all available studies and case reports of intramuscular methotrexate to examine the therapeutic efficacy, side-effects and complication rates of this new treatment approach. The pooled data show a successful resolution rate of 71% (95% confidence interval 58% to 81%) after a single dose of intramuscular methotrexate and 84% (95% confidence interval 77% to 90%) after 1 or 2 doses. Side-effects were experienced by 24% (95% confidence interval 9% to 47%) of patients and 10% (95% confidence interval 7% to 14%) had a ruptured ectopic pregnancy. The pooled data show that single-dose intramuscular methotrexate is associated with a high failure rate. Follow-up is prolonged and there is a significant incidence of minor side-effects. Serious complications and side-effects have occurred. The use of intramuscular methotrexate should be confined to clinical trials until more evidence is obtained to support its more widespread use.

Extragenital mullerian adenosarcoma with sarcomatous overgrowth arising in an endometriotic cyst in the pouch of Douglas.

Mullerian adenosarcoma is a neoplasm composed of benign mullerian epithelium and a sarcomatous stroma. This tumor classically occurs in the endometrium of postmenopausal women and less frequently in the extrauterine genital tract. Rare cases of extragenital adenosarcoma have been reported. We present the case of a 23-year-old female who presented with an extragenital adenosarcoma arising in an endometriotic cyst in the pouch of Douglas. The patient was treated with local excision, chemotherapy and radiotherapy. At 2 years follow-up she was disease-free. The literature on extragenital adenosarcoma is reviewed. These tumors are clinically more aggressive than their uterine counterparts. Surgical excision is the initial treatment modality for these patients. Little information is available regarding the efficacy of adjuvant chemotherapy or radiotherapy. This is an area that requires further study.