Cyclo-oxygenase-2 (Cox-2) expression and resistance to platinum versus platinum/paclitaxel containing chemotherapy in advanced ovarian cancer

Background  

Cyclo-oxygenase-2 (COX-2), the key enzyme in the conversion of arachidonic acid to prostaglandins, is involved in critical steps of tumor onset and progression, and is a strong predictor of chemotherapy resistance and poor outcome in advanced ovarian cancer. To our knowledge, no data has been reported until now about the association between COX-2 status and response to different chemotherapy regimens.     

Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients.

PURPOSE: Overexpression of beta III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of beta III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether beta III tubulin expression could be modified after the selective pressure represented by chemotherapy in vivo. EXPERIMENTAL DESIGN: The study was designed to include a series of consecutive ovarian cancer patients with unresectable disease at time of first surgery, who underwent interval debulking surgery with pathologic assessment of response to treatment with platinum/paclitaxel chemotherapy. Immunostaining was done on formalin-fixed, paraffin-embedded tissue sections from pretreatment and posttreatment tissue biopsies by using the polyclonal rabbit anti-class III beta-tubulin antibody. RESULTS: beta III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. beta III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of beta III tubulin positivity were observed in posttreatment (range, 5-80%; median, 20%) versus pretreatment (range 10-100%; median, 40%) tissue biopsies (P = 0.0011). Cases with high beta III tubulin expression showed a worse overall survival with respect to cases with low beta III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of beta III tubulin remains independently associated with a worse prognosis. CONCLUSIONS: Assessment of beta III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.     

Insomnia in general practice : a consensus report produced by sleep specialists and primary-care physicians in Italy

Insomnia is an extremely common condition with major social and economic consequences worldwide. Two large epidemiological studies (Morfeo 1 and Morfeo 2) recently performed in Italy provided much-needed novel data on the impact of insomnia in patients whose primary healthcare is provided by general practitioners (GPs). These studies found that insomnia is managed relatively well by GPs in Italy, although diagnosis and treatment can be compromised because of the lack of standardised criteria. Although a number of consensus reports on insomnia have been published, these are mainly highly specific documents that are difficult to implement in general practice. To address this, a consensus group involving 695 GPs and over 60 specialists from the Italian Association of Sleep Medicine was established. The major objectives of the consensus study were to establish basic knowledge for the diagnosis and treatment of insomnia, and to produce guidelines for the management of insomnia by GPs. This is the first time that GPs have been directly involved in producing insomnia guidelines of this type, and this approach reflects their pivotal role in the diagnosis and management of this condition. Participants were carefully selected to ensure adequate representation of sleep specialists and GPs, with the group being headed by a steering committee and an advisory board. Guideline statements were selected following careful literature review and were voted on using formalised consensus procedures. This review describes current views on the diagnosis and management of insomnia from the perspective of the GP. In addition, the results of the consensus study are presented. They include recognition of the following principles: (i) insomnia is a genuine pathology that must be appropriately diagnosed and treated; (ii) when concomitant pathologies are present, additional significance should be given to treatment of insomnia since it can influence prognosis of coexistent disorders; (iii) appropriate treatment should consider the cause of insomnia as well as the characteristics of available pharmacological agents; (iv) with regard to hypnotic drugs, preference should be given to medications with a short half-life in order to limit residual effects; (v) non-benzodiazepine hypnotics are preferred to classic benzodiazepines as they have higher selectivity and present a lower risk of undesirable effects; (vi) tablets are preferable to liquid preparations as they are less likely to lead to dependence and to overdosing by the patient; and (vi) once treatment has been initiated, insomnia patients should be carefully followed up. These statements provide much needed criteria for better management of insomnia by GPs in Italy.     

The effect of concomitant radiofrequency ablation and surgical technique (repair versus replacement) on release of cardiac biomarkers during mitral valve surgery

All patients undergoing heart surgery experience a certain amount of nonspecific myocardial injury documented by the release of cardiac biomarkers and associated with poor outcome. We investigated the role of unipolar radiofrequency ablation of atrial fibrillation on the release of cardiac biomarkers in 71 patients undergoing mitral valve surgery and concomitant left atrial ablation case-matched with 71 patients undergoing isolated mitral surgery. The study was powered to detect a 3 ng/mL difference. There was no difference between the 2 groups in terms of cardiac troponin I (10 +/- 5.3 versus 12 + 10.4 ng/mL; P = 0.7) or creatine kinase-MB (50 +/- 21.8 versus 57 +/- 62.0 ng/mL; P = 0.5) release. Postoperative peak cardiac troponin I levels had univariate associations with the duration of cardiopulmonary bypass (P = 0.002) and aortic cross-clamping (P = 0.001) and with the surgical technique (15 +/- 12 ng/mL for mitral valve replacement versus 9 +/- 4.8 for mitral valve repair; P = 0.0007) at univariate analysis. Mitral valve replacement was the only independent predictor of postoperative peak release of cardiac troponin I identified with multivariate analysis (P = 0.005). Radiofrequency ablation of atrial fibrillation does not significantly increase cardiac biomarker release compared with isolated mitral surgery; mitral valve repair is associated with less release of cardiac biomarkers compared with mitral valve replacement.     

Traffic air pollution and hospital admission for asthma: a case–control approach in a Turin (Italy) population

OBJECTIVES: This study investigated the relationship between traffic air pollution and asthma, using a case-control design applied to routinely collected data. METHODS: Subjects resident in Turin during the period 1997-1999 and admitted for asthma were defined as cases; patients admitted for causes other than respiratory diseases or heart diseases were defined as controls. Nitrogen dioxide and total suspended particulate were considered as indicators of traffic air pollution. Statistical analysis were performed, separately for young (0-14 years), adult (15-64 years) and elderly (>64 years) patients, with a logistic regression model; results are expressed as percentage of risk modification for a 10 g/m(3) increase in exposure to pollutants. RESULTS: The risk of emergency admissions for asthma rose significantly with increased exposure to nitrogen dioxide [2.4%, 95% Confidence Interval: 0.5%; 4.3%], and total suspended particulate [2.3%, 95% Confidence Interval: 1.1%-3.6%]. The significant association was evident, in particular, among young and elderly patients for both pollutants. CONCLUSION: Using a case-control design both easy to use and manage, the study confirms the significant association between hospital emergency admissions for asthma and exposure to nitrogen dioxide and total suspended particulate pollutants.     

Multiple lines of chemotherapy are the main risk factor for severe infections in patients with chronic lymphocytic leukemia with febrile episodes

We report on febrile episodes occurring among 379 patients affected by chronic lymphocytic leukemia, observed from 1984 to 2002. One hundred and twenty eight patients (33.7%) developed 341 febrile episodes, of which 251 were documented infections (82 severe and 169 moderate). Among various risk factors, only previous treatment with multiple regimens of chemotherapy was associated with severity of infection (p=0.0005).     

Newborns' preference for face-relevant stimuli: effects of contrast polarity

There is currently no agreement as to how specific or general are the mechanisms underlying newborns' face preferences. We address this issue by manipulating the contrast polarity of schematic and naturalistic face-related images and assessing the preferences of newborns. We find that for both schematic and naturalistic face images, the contrast polarity is important. Newborns did not show a preference for an upright face-related image unless it was composed of darker areas around the eyes and mouth. This result is consistent with either sensitivity to the shadowed areas of a face with overhead (natural) illumination and/or to the detection of eye contact.     

Color-coded automated signal intensity curves for detection and characterization of breast lesions: preliminary evaluation of a new software package for integrated magnetic resonance-based breast imaging

OBJECTIVES: The objective of this study was to evaluate the value of a color-coded automated signal intensity curve software package for contrast-enhanced magnetic resonance mammography (CE-MRM) in patients with suspected breast cancer. MATERIALS AND METHODS: Thirty-six women with suspected breast cancer based on mammographic and sonographic examinations were preoperatively evaluated on CE-MRM. CE-MRM was performed on a 1.5-T magnet using a 2D Flash dynamic T1-weighted sequence. A dosage of 0.1 mmol/kg of Gd-BOPTA was administered at a flow rate of 2 mL/s followed by 10 mL of saline. Images were analyzed with the new software package and separately with a standard display method. Statistical comparison was performed of the confidence for lesion detection and characterization with the 2 methods and of the diagnostic accuracy for characterization compared with histopathologic findings. RESULTS: At pathology, 54 malignant lesions and 14 benign lesions were evaluated. All 68 (100%) lesions were detected with both methods and good correlation with histopathologic specimens was obtained. Confidence for both detection and characterization was significantly (P < or = 0.025) better with the color-coded method, although no difference (P > 0.05) between the methods was noted in terms of the sensitivity, specificity, and overall accuracy for lesion characterization. Excellent agreement between the 2 methods was noted for both the determination of lesion size (kappa = 0.77) and determination of SI/T curves (kappa = 0.85). CONCLUSIONS: The novel color-coded signal intensity curve software allows lesions to be visualized as false color maps that correspond to conventional signal intensity time curves. Detection and characterization of breast lesions with this method is quick and easily interpretable.     

Blood lead levels, clinico-pathological findings and erythrocyte metabolism in dogs from different habitats

Biological markers of lead exposure were measured in 20 dogs from five different habitats chosen on the basis of the degree of anthropogenic influence. None of the dogs had clinical signs of lead poisoning. Compared to controls, blood lead concentrations were significantly higher in dogs from industrial areas, confirming the role of lead emissions in environmental pollution and the possible role of dogs as biomonitors of lead exposure in these areas. Whole blood lead concentrations were similar in dogs living in urban and rural areas, probably due to "indirect" lead sources and due to decreased urban lead contamination. As in humans, individual variability was detected. No significant correlation between clinico-pathological changes (hematology, clinical chemistry, Delta-aminolevulinic acid dehydratase activity and other intra-erythrocytic metabolic parameters) and lead concentration were observed. Our findings suggest dogs can be useful as sentinels of environmental lead exposure.     

Inner retinal abnormalities in a mouse model of Leber's congenital amaurosis

Leber's congenital amaurosis (LCA) is the earliest and most severe form in the world of genetic retinal dystrophy causing blindness. An animal model of LCA was recently created in which the cone-rod homeobox (crx) gene was disrupted using homologous recombination. Crx-/- mice display abnormal development of photoreceptors followed by their degeneration. We analyzed the morphology of inner retinal cells in crx-/- mice in order to evaluate the effects of abnormal photoreceptor development and death upon other retinal neurons. The identification of a time window during which inner retinal cells are still viable could be very important in view of the possibilities that photoreceptor transplantation or gene therapy might be used to restore vision in LCA. We used a combination of immunocytochemical and confocal microscopy techniques to screen the crx-/- inner retina and verify its morphological integrity after photoreceptor degeneration. We found significant morphological alterations in second-order neurons in crx-/- animals. The appearance of mutant retinas after photoreceptor death is indistinguishable from that of the retinal degeneration (rd/rd) mouse, a different genetic model of a retinal disease characterized by photoreceptor degeneration. However, at early stages of photoreceptor degeneration the morphology of retinal cells in the crx-/- mutant is considerably well preserved. It is likely that different genetic mechanisms that cause abnormal photoreceptor development and/or degeneration lead to a common pathway that determines second-order neuron modifications. The severity of modifications is linked to the timing of onset of the degeneration and appears to increase with time.