PCSK9 is associated with mortality in patients with septic shock: data from the ALBIOS study.

BACKGROUND: Pro-protein convertase subtilisin/kexin 9 (PCSK9) is a proenzyme primarily known to regulate low-density lipoprotein receptor re-uptake on hepatocytes. Whether PCSK9 can concurrently trigger inflammation or not remains unclear. Here, we investigated the potential association between circulating levels of PCSK9 and mortality in patients with severe sepsis or septic shock. METHODS: Plasma PCSK9 levels at days 1, 2 and 7 were measured in 958 patients with severe sepsis or septic shock previously enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial. Correlations between levels of PCSK9 and pentraxin 3 (PTX3), a biomarker of disease severity, were evaluated with ranked Spearman's coefficients. Cox proportional hazards models were used to assess the association of PCSK9 levels at day 1 with 28- and 90-day mortality. RESULTS: Median plasma PCSK9 levels were 278 [182-452] ng mL-1 on day 1. PCSK9 correlated positively with PTX3 at the three time-points, and patients with septic shock within the first quartile of PCSK9 showed higher levels of PTX3. Similar mortality rates were observed in patients with severe sepsis across PCSK9 quartiles. Patients with septic shock with lower PCSK9 levels on day 1 (within the first quartile) showed the highest 28- and 90-day mortality rate as compared to other quartiles. CONCLUSION: In our sub-analysis of the ALBIOS trial, we found that patients with septic shock presenting with lower plasma PCSK9 levels experienced higher mortality rate. Further studies are warranted to better evaluate the pathophysiological role of PCSK9 in sepsis.

Phase 2 study of anastrozole in rare cohorts of patients with estrogen receptor/progesterone receptor positive leiomyosarcomas and carcinosarcomas of the uterine corpus: The PARAGON trial (ANZGOG 0903).

BACKGROUND: Aromatase inhibitors have been used empirically to treat a subset of patients with hormone receptor positive uterine leiomyosarcomas(LMS) and carcinosarcomas (UCS) mainly supported by retrospective data. We evaluated the activity of anastrozole in two rare cohorts; patients with recurrent/metastatic LMS and UCS enrolled in PARAGON, a basket trial of anastrozole in estrogen receptor (ER+)/progesterone receptor positive (PR+) gynecological cancers. METHOD: An investigator-initiated, single-arm, prospective open-label trial of anastrozole 1 mg/day in patients with ER &/or PR + ve LMS or UCS with measurable disease, treated until progression or unacceptable toxicity. Primary endpoint was clinical benefit (complete/partial response + stable disease) rate (CBR) at 3 months. Secondary endpoints include progression-free survival (PFS), quality of life and toxicity. RESULTS: 39 eligible patients were enrolled, 32 with LMS and 7 with UCS. For the LMS cohort CBR at 3 months was 35% (95% CI: 21-53%) with a median duration of clinical benefit of 5.8 months. Best response was a partial response in one patient. Two patients remained on treatment for more than one year. The median progression-free survival was 2.8 months (95% CI: 2.6-4.9). For the UCS cohort CBR at 3 months was 43% (95% CI: 16-75%) with a median duration of clinical benefit of 5.6 months. Stable disease was seen in 3 patients but no objective responses were seen. The median progression-free survival was 2.7 months (95% CI, 1.1-8.2). Safety was acceptable with 5/39 evaluable patients showing grade 3 toxicities. CONCLUSION: Whilst objective response rates with anastrozole are low, the clinical benefit rate and good tolerance suggests that aromatase inhibitor therapy may have a role in a subset of patients with metastatic LMS and UCS.

Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT-2 inhibitors and GLP-1 receptor agonists.

Patients with type 2 diabetes mellitus (T2D) present an increased risk for cardiovascular (CV) complications. In addition to improvement in glycaemic control, glucose-lowering therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-dependent glucose cotransporter (SGLT)-2 inhibitors, have been shown to significantly reduce CV events. In 2008, the US Food and Drug Administration mandated that all new glucose-lowering drugs undergo CV outcomes trials (CVOTs) to determine their CV safety. These trials have largely demonstrated no major CV safety concerns. Most notably, the GLP-1RAs and SGLT-2 inhibitors have been found to be not only safe, but also cardioprotective compared to placebo. The SGLT-2 inhibitors have opened a new perspective for clinicians treating patients with T2D and established CV disease in light of their 'pleiotropic' effects, specifically on heart failure, while GLP-1RAs seem to present more favourable effects on atherosclerotic events. In this review, we discuss the role of GLP-1RAs and SGLT-2 inhibitors to reduce CV risk in T2D patients and suggest an individualized therapeutic approach in this population based on the presence of metabolic and CV comorbidities.

High serum levels of C-reactive protein (CRP) predict beneficial decrease of visceral fat in obese females after sleeve gastrectomy.

BACKGROUND & AIMS: Gender-related differences represent an emerging investigation field to better understand obesity heterogeneity and paradoxically associated cardiovascular (CV) risk. Here, we investigated if high-sensitivity C-reactive protein (hs-CRP) might differently affect adiposity and predict the clinical response to bariatric surgery in obese males and females. METHODS AND RESULTS: In 110 morbidly obese patients undergoing laparoscopic sleeve gastrectomy, hs-CRP as well as anthropometric assessment of adiposity, completed by electric bioimpedance and ultrasonography quantification of visceral fat area (VFA), were measured before and one year after surgery. As compared to males, obese female showed less severe overweight and prevalent subcutaneous fat deposition, but higher circulating hs-CRP. In obese females, hs-CRP was associated with VFA at baseline, independently of body mass index (BMI) and visceral adiposity index (OR 1.022 [95% CI 1.001-1.044]; p = 0.039). Based on decreases and increases in hs-CRP levels after surgery, two distinct subgroups of females were identified. Post-surgery decreases in hs-CRP was predominantly observed in patients with higher baseline levels of hs-CRP and associated with greater reduction of weight, BMI, fat and lean mass, VFA and visceral to subcutaneous fat ratio. Finally, we observed that high baseline values of hs-CRP were able to predict VFA reduction one-year after surgery, independently of BMI and visceral adiposity index (VAI) loss (OR 1.031 [95% CI 1.009-1.053]; p = 0.005). CONCLUSION: In obese females, hs-CRP levels might be a promising biomarker of visceral fat amount and dysfunction, in addition to predict the effectiveness of bariatric surgery in terms of loss of VFA one-year after surgery.

High baseline C-reactive protein levels predict partial type 2 diabetes mellitus remission after biliopancreatic diversion.

BACKGROUND AND AIMS: Several studies demonstrated that surgery can improve inflammation parameters, such as C-reactive protein (CRP). Few biomarkers have been investigated to potentially predict type 2 diabetes mellitus (T2DM) remission. We aimed at determining whether pre-surgery serum CRP levels could predict T2DM remission after 3 years in patients undergoing bariatric surgery, especially biliopancreatic diversion (BPD). METHODS AND RESULTS: This study was conducted from 2007 to 2009 at the Surgical Department of the University of Genoa, Italy. Forty-four patients with T2DM undergoing BPD (n = 38) or Roux-en-Y gastric bypass (n = 6) were enrolled. The primary endpoint was to evaluate whether pre-surgery CRP levels could predict T2DM partial remission at 3-year follow-up. Secondary endpoints were to assess whether glycaemic, lipid, and inflammatory parameters modified during the follow-up. At baseline, patients with T2DM ranged from overweight to morbid obesity, had mild dyslipidaemia, and a low-grade inflammation. Bariatric surgery improved body weight, lipid and glycaemic profile both at 1- and 3-year follow-up. Pre-surgery CRP levels progressively decreased at 1- and 3-year follow-up. Among inflammatory pre-surgery parameters, only high CRP levels were shown to predict T2DM partial remission after 3 years. Multivariate analysis confirmed the predictive value of pre-surgery CRP levels independently of age, gender, type of surgery, and body mass index. CONCLUSION: Bariatric surgery, in particular BPD, improved both metabolic and inflammatory biomarkers at 1- and 3-year follow-up. Pre-surgery high CRP levels predicted 3-year T2DM partial remission, indicating a promising target population to be especially treated with BPD.

Comparison of vildagliptin and glimepiride: effects on glycaemic control, fat tolerance and inflammatory markers in people with type 2 diabetes.

AIMS: To compare the effects of vildagliptin with those of glimepiride on glycaemic control, fat tolerance and inflammatory markers in people with Type 2 diabetes mellitus receiving metformin treatment. METHODS: A total of 167 participants were randomized to vildagliptin 50 mg twice a day or glimepiride 2 mg three times a day, for 6 months. We evaluated the following variables: BMI; glycaemic control; fasting plasma insulin; homeostatic model assessment of insulin resistance index; fasting plasma proinsulin; glucagon; lipid profile; adiponectin; high-sensitivity C-reactive protein; interleukin-6; and tumour necrosis factor-α. A euglycaemic-hyperinsulinaemic clamp procedure and an oral fat load test were also performed. RESULTS: Despite a similar decrease in HbA1c levels (P = 0.009, and P = 0.008, respectively), body weight increased with glimepiride (P = 0.048 vs baseline) and decreased with vildagliptin (P = 0.041 vs baseline and vs glimepiride). Fasting plasma insulin and homeostatic model assessment of insulin resistance index were significantly lower with vildagliptin compared with glimepiride (P = 0.035 and 0.047). M value, an index of insulin sensitivity, increased with vildagliptin, both compared with baseline and with glimepiride (P = 0.028 and 0.039, respectively). Vildagliptin improved all post-oral fat load peaks of lipid profile compared with glimepiride. Adiponectin levels were higher (P = 0.035) and high-sensitivity C-reactive protein levels were lower (P = 0.038) with vildagliptin vs glimepiride. During the oral fat load test, interleukin-6, high-sensitivity C-reactive protein and tumour necrosis factor-α peaks were lower and adiponectin peak was higher in the vildagliptin group than in the glimepiride group. There was a higher dropout rate as a result of hypoglycaemia in the glimepiride group than in the vildagliptin group. CONCLUSIONS: Vildagliptin was more effective than glimepiride in reducing post-oral fat load peaks of lipid-trafficking adipocytokines and inflammatory markers.

A randomized, placebo-controlled study on the effects of a nutraceutical combination of red yeast rice, silybum marianum and octasonol on lipid profile, endothelial and inflammatory parameters.

The aim of this study was to evaluate the effects of a combination of red yeast rice, Silybum marianum and octasonol compared to placebo on lipid profile, endothelial, and inflammatory parameters in low risk dislipidemic patients. One hundred and thirty-four dislipidemic patients were randomised to take placebo or a patented nutraceutical association in tablet form (Zeta ColestRT), 1 tablet /day (immediately after the dinner), for three months in a double-blind, placebo-controlled trial. At baseline and after 3 months the following were evaluated: body weight, body mass index (BMI), fasting plasma glucose (FPG), lipid profile, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), metalloprotineases-2 and -9 (MMP-2 and MMP-9), high sensitivity C-reactive protein (Hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). The nutraceutical combination decreased total cholesterol and low density lipoprotein cholesterol compared to baseline (p = 0.042, and p = 0.041, respectively) and to placebo (p = 0.039, and p = 0.037, respectively). Triglycerides were reduced by the active treatment (p = 0.039), but not by placebo, even if, in group to group comparison, no differences were recorded (p = 0.061). All adipocytokines were reduced by the nutraceutical combination, in particular p = 0.044 for sICAM-1, p = 0.045 for sVCAM-1, p = 0.040 for sE-selectin, p = 0.035 for MMP-2, p = 0.039 for MMP-9, p = 0.038 for Hs-CRP, p = 0.036 for TNF-α, and p = 0.036 for IL-6 compared to baseline, and p = 0.042 for sICAM-1, p = 0.043 for sVCAM-1, p = 0.042 for sE-selectin, p = 0.031 for MMP-2, p = 0.038 for MMP-9, p =0.038 for Hs-CRP, and p = 0.043 for TNF-alpha, espectively, compared to placebo. We can conclude that a combination of red yeast rice, Silybum marianum and octasonol was effective in improving lipid profile, endothelial, and inflammatory parameters in low risk dislipidemic patients.

Effects of enalapril/lercanidipine combination on some emerging biomarkers in cardiovascular risk stratification in hypertensive patients.

WHAT IS KNOWN AND OBJECTIVE: There is considerable interest in pharmacogenetic and molecular biomarkers. Our aim was to evaluate the effects of enalapril/lercanidipine combination on some emerging biomarkers for cardiovascular risk stratification of hypertensive patients, such as lipoprotein(a) [Lp(a)], soluble advanced glycation end products (sRAGE), soluble CD40 ligand (sCD40L) and serum myeloperoxidase (MPO). RESEARCH DESIGN AND METHODS: Three hundred and forty-five patients were enrolled in this randomized, double-blind, clinical trial: 120 hypertensive patients were randomized to enalapril 20 mg, 110 to lercanidipine 10 mg and 115 to enalapril/lercanidipine 20/10 mg fixed combination. We measures the following markers at baseline and after 6, 12, 18 and 24 months: blood pressure, fasting plasma glucose (FPG), lipid profile, Lp(a), sRAGE, sCD40L and MPO. RESULTS: There was a decrease in blood pressure in all groups compared with baseline, even if, as expected, enalapril/lercanidipine combination was more effective in reducing blood pressure compared with the monotherapies. No variations in lipid profile or FPG were recorded in any of the groups. Lercanidipine, but not enalapril, improved Lp(a) levels compared with baseline. The combination enalapril/lercanidipine improved it more than the single therapies. All treatments increased sRAGE levels, and decreased sCD40L and MPO, with a better effect seen with the enalapril/lercanidipine combination compared with single monotherapies. WHAT IS NEW AND CONCLUSION: The combination enalapril/lercanidipine seems to be better than the single monotherapies in reducing not only blood pressure, but also the levels of some emerging biomarkers, potentially useful for cardiovascular risk stratification of hypertensive patients.

Effects of Berberis aristata/Silybum marianum association on metabolic parameters and adipocytokines in overweight dyslipidemic patients.

Nutraceuticals and functional foods have attracted considerable interest as potential alternative therapies for treatment of different cardiovascular disorders and insulin resistance. We evaluated the efficacy of a combination of Berberis Aristata/Silybum Marianum extract (Berberol®) in a sample of overweight, dyslipidemic patients at low cardiovascular risk. We enrolled 105 Caucasian, euglycemic, overweight, dyslipidemic patients, of either sex. At baseline all patients underwent a 6 months run-in period during which they followed an adequate diet and practiced physical activity. At the end of the run-in period, patients were randomised to take placebo or a combination of Berberis aristata/Silybum marianum, 1 tablet during the lunch and 1 tablet during the dinner, for three months, in a double-blind, placebo-controlled design. Berberis aristata/Silybum marianum and placebo were then interrupted for 2 months (wash-out period), and all patients continued with only diet and physical activity. At the end of the wash-out period, patients re-started Berberis aristata/Silybum marianum or placebo twice a day for further 3 months. We evaluated during the run-in period, at randomisation, before and after the wash-out period these parameters: body weight and BMI, fasting plasma glucose, lipid profile, insulin resistance, retinol binding protein-4 (RBP-4), adiponectin (ADN), resistin. Total cholesterol, LDL-C, and Tg decreased, and HDL-C increase after 3 months of Berberis aristata/Silybum marianum, both compared to baseline and placebo. Berberis aristata/Silybum marianum decreased fasting plasma insulin, and HOMA-IR, both compared to baseline and to placebo. Moreover, there was a decrease of RBP-4, and resistin, and an increase of ADN after 3 months of Berberis aristata/Silybum marianum. All these positive effects disappeared after the wash-out period, and re-appeared after the re-introduction of the drug. We observed a significant correlation between HOMA-index decrease and resistin, and RBP-4 decrease, and between HOMA-index decrease and ADN increase in Berberis aristata/Silybum marianum group, but not in placebo group. Berberis aristata/Silybum marianum fixed combination seems to be safe and effective in improving lipid profile, but also in improving insulin resistance and adipocytokines levels.

Administration of chemotherapy with palliative intent in the last 30 days of life: the balance between palliation and chemotherapy.

BACKGROUND: Appropriately timed cessation of chemotherapy is an important aspect of good quality palliative care. There is wide variation in the reported rates of chemotherapy administration within the last 30 days of life. AIMS: To identify predictors of death within 30 days of receiving palliative chemotherapy, and to propose a standard definition by which oncologists and cancer centres can be compared. METHODS: Patients who received palliative chemotherapy at a regional cancer centre and its rural outreach unit between 2009 and 2011 were included. An adjusted logistic regression model, including all variables, was fit to identify predictors of death within 30 days of receiving palliative chemotherapy. RESULTS: Over a 3-year period, 1131 patients received palliative chemotherapy, 138 (12%) died within 30 days of receiving palliative chemotherapy. Predictors of death within 30 days of palliative chemotherapy were: less than 30 days contact with palliative care (odds ratio 3.30 (95% confidence interval 2.04-5.34), P < 0.001) and male gender (odds ratio 2.02 (95% confidence interval 1.24-3.31), P = 0.0049), but treating clinician, tumour chemoresponsiveness, age, body mass index and survival from initial diagnosis were not. CONCLUSION: Patients who received chemotherapy in the last 30 days of life were more likely to be male and have a shorter duration of palliative care team involvement. In this study, the observed rate of death within 30 days of chemotherapy is within the range of published data. It is recommended that a standard definition be used to benchmark medical oncology centres and individual oncologists, and to allow comparison over time.

Turgor loss point and vulnerability to xylem embolism predict species-specific risk of drought-induced decline of urban trees.

Increasing frequency and severity of drought events is posing risks to trees' health, including those planted in urban settlements. Drought-induced decline of urban trees negatively affects ecosystem services of urban green spaces and implies cost for maintenance and removal of plants. We aimed at identifying physiological traits that can explain and predict the species-specific vulnerability to climate change in urban habitats. We assessed the relationships between long-term risk of decline of different tree species in a medium-sized town and their key indicators of drought stress tolerance, i.e. turgor loss point (TLP) and vulnerability to xylem embolism (P50 ). Starting from 2012, the study area experienced several summer seasons with positive anomalies of temperature and negative anomalies of precipitation. This trend was coupled with increasing percentages of urban trees showing signs of crown die-back and mortality. The species-specific risk of decline was higher for species with less negative TLP and P50 values. The relationship between species-specific risk of climate change-induced decline of urban trees and key physiological indicators of drought tolerance confirms findings obtained in natural forests and highlights that TLP and P50 are useful indicators for species selection for tree plantation in towns, to mitigate negative impacts of climate change.

Resistin is associated with overall survival in non-small cell lung cancer patients during nivolumab treatment.

PURPOSE: Since the role of resistin was evaluated only in patients with non-small cell lung cancer (NSCLC) not treated with immunotherapy, we aimed to evaluate levels of resistin during immunotherapy (nivolumab) and its prognostic role with regard to OS. METHODS/PATIENTS: From a cohort of 78 patients with advanced NSCLC enrolled in a prospective study at Ospedale Policlinico San Martino in Genoa (Italy), 43 patients have been considered for this sub-analysis because of the availability of samples. Before and during nivolumab administration, clinical information and blood samples were collected and resistin, matrix metalloproteinase (MMP)-8, MMP-9, and myeloperoxidase were evaluated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Median age was 71 with a prevalence of males and former smokers. Median resistin levels presented a peak at cycle 2 and then dropped down until the last cycle. Resistin correlated with all neutrophil degranulation products at cycle 1 (except for MMP-9) and at cycle 2 as well as with white blood cells and neutrophils. By a ROC curve analysis, a resistin value at cycle 2 of 19 ng/mL was tested as the best cut-off point for OS. Kaplan-Meier analysis demonstrated that patients above the resistin cut-off experienced a reduced OS (median OS 242.5 vs. 470 days, p = 0.0073), as confirmed by Cox proportional hazards regression analysis. CONCLUSIONS: Resistin levels > 19 ng/mL at the time of the second cycle of nivolumab treatment independently predict a reduced OS in patients with advanced NSCLC.

Serum levels of osteopontin predict diabetes remission after bariatric surgery.

AIM: Bariatric surgery has been shown to effectively improve glycaemic control in morbidly obese subjects. However, the molecular bases of this association are still elusive and may act independently of weight loss. Here, our retrospective study has investigated the inflammatory molecule osteopontin (OPN) as a potential predictor of type 2 diabetes mellitus (T2DM) remission. METHODS: Baseline serum levels of OPN were analyzed in 41 T2DM patients who underwent bariatric surgery. Anthropometric measures and biochemical variables, including insulin sensitivity indices (HOMA2), were assessed at baseline and at 1 and 3 years after surgery. RESULTS: At baseline, patients who experienced T2DM remission had increased waist circumference, body weight and BMI, and higher serum OPN, compared with non-remitters. Patients with and without T2DM remission improved their lipid and glucose profiles, although insulin resistance indices were only improved in the T2DM remission group. In the overall cohort of both T2DM remission and non-remission patients, baseline circulating levels of OPN significantly correlated with reductions of body weight and BMI over time, and insulin sensitivity improved as well. However, only the HOMA2-%S remained independently associated with serum OPN on multivariate linear regression analysis (B: 0.227, 95% CI: 0.067-0.387, ß = 0.831; P = 0.010). Baseline values of OPN predicted 3-year T2DM remission independently of body weight loss, lower BMI and duration of diabetes (OR: 1.046, 95% CI: 1.004-1.090; P = 0.033). CONCLUSION: Although larger studies are still needed to confirm our preliminary results, pre-operative OPN serum levels might be useful for predicting 3-year T2DM remission independently of weight loss in patients undergoing bariatric surgery.

Simultaneous adjuvant radiation therapy and chemotherapy in high-risk breast cancer--toxicity and dose modification: a Transtasman Radiation Oncology Group Multi-Institution study.

PURPOSE: To establish the toxicity profile of simultaneously administered postoperative radiation therapy and CMF chemotherapy as a prelude to a randomized controlled study addressing the sequencing of the two modalities. METHODS AND MATERIALS: One hundred and thirty eight breast cancer patients at high risk of locoregional, as well as systemic relapse, who were referred to three centers in Australia and New Zealand were treated with postoperative radiation therapy and chemotherapy simultaneously. Acute toxicity and dose modifications in these patients were compared with 83 patients treated over the same time frame with chemotherapy alone. In a separate study the long-term radiation and surgical effects in 24 patients treated simultaneously with radiation therapy and chemotherapy at Newcastle (Australia) following conservative surgery were compared with 23 matched patients treated at Newcastle with radiation therapy alone. RESULTS: Myelotoxicity was increased in patients treated simultaneously with radiation therapy and chemotherapy. The effect was not great, but may have contributed to chemotherapy dose reductions. Lymphopenia was observed to be the largest factor in total white cell depressions caused by the simultaneous administration of radiation therapy. Postsurgical appearances were found to so dominate long-term treatment effects on the treated breast that the effect of radiation therapy dose and additional chemotherapy was difficult to detect. CONCLUSION: Studies addressing the sequencing of radiation therapy and chemotherapy will necessarily be large because adverse effects from administering the two modalities simultaneously are not great. The present study has endorsed the importance in future studies of stratification according to the extent and type of surgery and adherence to a single strict policy of chemotherapy dose modification.

Pelvic radiotherapy with concurrent 5-fluorouracil modulated by leucovorin for rectal cancer: a phase II study.

Combined modality treatment for cancer of the rectum has been shown to reduce recurrences and improve overall survival. We wished to find out if we could safely give concurrent radiotherapy and 5-fluorouracil (5-FU) modulated by leucovorin (LV) in 3 settings: pre-operatively, adjuvantly and in recurrent disease. A total of 39 patients were treated, 11 preoperatively, 17 adjuvantly and 11 with recurrent disease. There were 26 males and 13 females with a median age of 64 years. The median radiotherapy (RT) dose was 45 Gy/25 fractions/1.8 Gy per fraction (range 25-63 Gy). Chemotherapy consisted of LV 80 mg/m2 i.v. infusion over 1.5 hours followed by 5-FU 400 mg/m2 i.v. bolus, both given once a week. The median number of cycles was 8 (range 3-12). Diarrhoea was the main toxicity, and was encountered in 30 patients (77%): grade 1 in 3 (8%), grade 2 in 12 (30%), grade 3 in 11 (28%), and grade 4 in 4 (10%). This required 18 (46%) patients to have modifications to their RT (20% had breaks and 26% ceased at doses < 45 Gy). Nine patients (23%) had modifications in the chemotherapy (10% had breaks and 13% received < 6 cycles). Encouraging responses were seen in the preoperative setting. Concurrent RT and 5-FU/LV, as given in this schedule, results in an unacceptable incidence of diarrhoea, limiting both the total dose of RT and chemotherapy that can be delivered, particularly in patients who have had previous surgery.

[Echography and hysteroscopy. 2 diagnostic technics compared in the identification of endometrial lesions in the postmenopause]. / Ecografia e isteroscopia. Due tecniche diagnostiche a confronto nell'identificazione delle lesioni endometriali in postmenopausa.

METHODS: In this study we compared ultrasonographic scanning of the endometrium and the hysteroscopic view with histology obtained by endometrial biopsy. RESULTS: Forty six postmenopausal women were studied, 25 symptomatic and 21 asymptomatic. In 24 cases endometrial thickness was > 5 mm, it was considered abnormal, and in 12 cases was < 5 mm. Hysteroscopy detects the presence of 7 atrophic endometrium, 19 polyps, 8 myomas, 4 cancer, 5 synechiae. Echography had a sensitivity of 90.9%, specificity of 72% and positive predictive value of 90.9%. Hysteroscopy showed a sensitivity of 96.7%, a specificity of 92.8% and a positive predictive value of 96.8%. CONCLUSIONS: In conclusion we may suggest that TV scanning allows detection of endometrial pathology with a high sensitivity so it may be used as the first diagnostic step in the screening of postmenopausal women, but it should be completed by hysteroscopic evaluation when endometrial thickness is > 5 mm also in asymptomatic women in order to detect cancer in a early stage.

[Effects of prolonged administration of dapiprazole in rats]. / Effetti di una prolungata somministrazione di dapiprazolo nel ratto.

In this paper we have studied the rat under chronic treatment with dapiprazole ip. (a drug with alpha-adrenergic blocking properties). For a 4 week period we have recorded, once a week, weight, rectal temperature, tail-flick, general activity and explorative behaviour on rotarod and one-arm radial maze. Surface (SEEG) and deep (DEEG) EEGrams were also recorded at the end of the experiments (4th week). SEEG and DEEG underwent the Fourier analysis (Fast Fourier Transform--see text). The findings were: 1) No change was observed in weight, rectal temperature and tail-flick time, glycemia and haematocrit. 2) Motor coordination on rotaroad dropped in 1st and 3rd week of treatment. 3) The treated rats, when in a one arm radial maze, showed signs of sedation (no grooming) from 2nd week of treatment. 4) SEEG and DEEG recordings showed a slowing activity; Fourier analysis confirmed these results. The slowing of activity (4) well agrees with the signs of sedation and behaviour (2, 3). It seems thus confirmed that alpha-adrenergic blockade is a feature of the drug together with the psychotropic effects previously described.