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.     

Mother-to-child HIV-1 transmission: Quantitative assessment of viral burden as a diagnostic tool and prognostic parameter in HIV-1-infected children

Polymerase chain reaction was performed in 251 infants born to HIV-1-seropositive mothers to diagnose HIV-1 infection. Assay specificity was invariably > 95%, regardless of age at testing, while sensitivity ranged from 15% in neonates (within 48 h of birth) to > 95% in infants over 1 month of age. Evaluation of viral burden in 43 infected infants by means of quantitative DNA-PCR disclosed that the number of HIV-1 proviruses ranged from 5 to 947 per 100,000 peripheral blood mononuclear cells. Clinical follow-up demonstrated that a high viral burden was associated significantly with disease onset.     

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.     

Effect of cyclosporine, mycophenolate mofetil, and their combination with steroids on apoptosis in a human cultured monocytic U937 cell line

Transplant patient plasma produces an increased rate of mononuclear cell apoptosis despite a normal serum creatinine value. Immunosuppressive medications may be one factor that causes an altered apoptotic pattern. We evaluated the in vitro effects of various doses of cyclosporine, mycophenolate mofetil, and steroids on apoptosis of a cultured human monocytic U937 cell line, using estimates by fluorescence microscopy and annexin V assays. Increasing cyclosporine concentrations (100 to 800 ng/mL) progressively increased apoptosis rates (16% to 32%). The combination of steroid (0.01 microg/mL) and cyclosporine increased the apoptosis rate to 45%. Mycophenolate mofetil alone (0.3 microg/mL) led to an apoptosis rate of 34%. Therapeutic levels of mycophenolate mofetil from 3 to 7 microg/mL led to apoptosis rates from 56% to 67%. The combination of cyclosporine, steroid, and mycophenolate mofetil increased the rate of apoptosis to 95%. Immunosuppressive therapy may contribute to the high rate of apoptosis observed among mononuclear cells of transplanted patients. This effect may alter patient susceptibility to infections and contribute to a unique mechanism of immunosuppression.     

Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature

We studied the genotype/phenotype correlation in a cohort of glycogen storage disease type (GSD) 1b patients. A total of 25 GSD1b patients, 13 females and 12 males, age range: 4.3–28.4 years, mean:14.6±6.8 years; median: 15 years, representing the entire case load of Italian GSD1b patients, were enrolled in the study. Molecular analysis of the glucose 6-phosphate translocase (G6PT1) gene was performed in all patients. We analysed the presence of a correlation among both the clinical features associated with GSD1b (neutropenia, frequency of admission to the hospital for severe infections) and the presence of systemic complications (liver adenomas, nephropathy, bone mineral density defect, polycystic ovaries, short stature, inflammatory bowel disease) and the mutations detected in each patient. Nine patients were homozygous or compound heterozygous for mutations causing stop codons. In particular, three patients were homozygous for the same mutation (400X); of these patients, one showed chronic neutropenia with severe and frequent infections and severe inflammatory bowel disease, another patient cyclic neutropenia associated with rare bacterial infections and mild bowel involvement and the last one normal neutrophil count. Two patients were homozygous for the mutation 128X; one of these patients did not show neutropenia, whereas the other one had severe neutropenia needing frequent hospital admission and was under granulocyte-colony stimulating factor treatment. In three patients no mutations were detected. Conclusion:no correlation was found between individual mutations and the presence of neutropenia, bacterial infections and systemic complications. These results suggest that different genes and proteins modulate neutrophil differentiation, maturation and apoptosis and thus the severity and frequency of infections. The absence of detectable mutations in three patients could suggest that a second protein plays a role in microsomal phosphate transport.     

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.