Is salvage chemotherapy for metastatic breast cancer always effective and well tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin

Metastatic breast cancer remains an incurable disease and the median overall survival has not significantly improved over the past two decades. Aims of the present randomized phase II trial were to analyse activity and toxicity of chemotherapies with single agent or with combination regimens in previously treated patients with advanced breast cancer. Ninety-nine eligible patients were randomized to receive the following chemotherapies: Arm A – 30mg/m² i.v. weekly; Arm B – leucovorin 100mg/m² i.v. followed by 5-fluorouracil 370mg/m² i.v. days 15, q 28days; Arm C – mitoxantrone 12mg/m² i.v. only day 1+leucovorin 100mg/m² i.v. followed by 5-fluorouracil 370mg/m² i.v. days 13, q 28days. Patients characteristics are comparable in the three groups. The median number of chemotherapy courses administered was 7, 6 and 5 in arm A, B and C, respectively. Objective responses were 24%, 30% and 21% and the median duration of responses were 2, 2.5 and 5.5 months in the arm A, B and C, respectively. Median overall survivals were 9.5, 9 and 9 months in the three arms. No difference was noted comparing the survivals of responding or non responding patients. General toxicity was not mild, with 27.5% of patients experiencing WHO grade 3–4 toxicities.Our results are similar in the three groups of patients and comparable to those reported by other authors. Chemotherapy applied to patients with second or subsequent recurrence allow objective responses in a small percentage of patients. Moreover responders have a negligible prolongation of survival.     

Abnormalities of the cardiovascular response to cold pressor test in type 1 diabetes. Correlation with blood glucose control

Left-ventricular (LV) function in type 1 diabetics without clinical heart disease was compared with that found in matched normal subjects. Although diabetics had a normal LV ejection fraction (66% +/- 6%), they showed a trend toward smaller left ventricles. Their cardiovascular response to a cold pressor test was abnormal and cardiac function after the cold pressor test correlated with hemoglobin A1c levels: Average hemoglobin A1c was inversely related to ejection fraction and early filling volume and directly related to the ratio of pre-ejection period to ejection time (PEP/LVET) after a cold pressor test. Hemoglobin A1c at the time of study correlated more closely with PEP/LVET after cold pressor test than did the six-month average hemoglobin A1c level, suggesting that cardiac function fluctuates with recent changes in blood glucose control. Thus, even when diabetics have a normal LV ejection fraction, an abnormal cardiovascular response to stress may still be present, and such abnormalities correlate with blood glucose control.     

Diclofenac and pirprofen modify pituitary and hypothalamic beta-endorphin concentrations

We provide evidence that both Diclofenac and Pirprofen, two cyclooxygenase inhibitors with a potent analgesic effect both in the experimental animal and in man, induce a significant and long lasting decrease in pituitary beta-endorphin concentrations, together with an increase of the hypothalamic concentrations of the peptide. We suggest that this effect might participate in the potent analgesic effect of the two compounds, that exceeds the one expected by drugs of this class.     

Bioinformatic methods for integrating whole-genome expression results into cellular networks

Extracting a comprehensive overview from the huge amount of information arising from whole-genome analyses is a significant challenge. This review critically surveys the state of the art methods that are used to connect information from functional genomic studies to biological function. Cluster analysis methods for inferring the correlation between genes are discussed, as are the methods for integrating gene expression information with existing information on biological pathways and the methods that combine cluster analysis with biological information to reconstruct novel biological networks.     

A doctor on the front line: Enrico Pajes (1912-1993)

We conducted an interview in the summer and autumn of 1991 with Dr Enrico Chaim Pajes, a Jewish Polish doctor who trained in Italy before World War II. Pajes was arrested when Italy entered the war in 1940. For the next three years he was rotated through various prisons. He witnessed the bombing of Campagna in 1943 and risked his life to treat the wounded. After the war he started a new life as the head of a medical clinic for Jewish displaced persons in Grottaferrata, in the suburbs of Rome. How did a Jew of Polish origin end up practising medicine in Italy for over 40 years? This oral history is the story of Enrico Pajes's life.     

Glycemic index, glycemic load and risk of prostate cancer

Dietary carbohydrates have different glycemic and insulinemic potentials depending on type (glycemic index, GI) and amount (glycemic load, GL) of carbohydrate consumed or both. Insulin in turn has been implicated as a risk factor for several cancers, including that of the prostate. We assessed the relationship of GI and GL with prostate cancer risk in a multicenter case-control study. Cases and controls were recruited between 1991 and 2002 in the network of major teaching and general hospitals in 4 Italian areas. Cases were 1,204 men (age range 46-74 years) admitted for incident, histologically confirmed prostate cancer. Controls were 1,352 men (age range 46-74 years) admitted for acute, nonmalignant conditions unrelated to long-term modifications of diet. ORs of prostate cancer and the corresponding 95% CIs were derived using unconditional multiple logistic regression, including terms for age, study center, education, family history of prostate cancer, smoking, body mass index, physical activity, alcohol consumption, intake of energy, fiber and lycopenes. Compared to the lowest quintile of GI, the ORs were 1.23, 1.24, 1.47 and 1.57 for subsequent levels of GI. The corresponding values for GL were 0.91, 1.00, 1.20 and 1.41. No heterogeneity was found among strata of selected covariates. We found direct relations between dietary GI and GL and prostate cancer risk. Correcting for potential confounding factors did not substantially modify these associations.     

Effects of long-term exposure of lemon essential oil odor on behavioral, hormonal and neuronal parameters in male and female rats

Behavioral, hormonal and neuronal responses to prolonged exposure to the volatile components of essential oil (EO) extracted from citrus lemon were investigated in male and female rats. Animals were exposed to the lemon essence for 2 weeks while in their cage. Anxiety was then determined with the elevated plus-maze apparatus while nociception was evaluated with a phasic thermal pain stimulus (plantar test) and with a chemical pain stimulus (formalin test). At the end of the experimental sessions, brain areas were dissected to measure beta-endorphin (beta-EP) concentrations in the hypothalamus and periaqueductal gray matter (PAG). Blood samples were collected to determine corticosterone plasma levels. In both sexes, prolonged EO exposure decreased the time spent in the open arms of the plus-maze apparatus. EO-exposed males and females showed higher thermal nociceptive thresholds than controls when tested with the plantar test apparatus. EO exposure induced female-specific decreases in formalin-induced pain behaviors during the formalin test. beta-EP concentrations in the hypothalamus and PAG were affected by EO. Corticosterone was lower in EO-exposed animals of both sexes than in their controls. These results suggest that long-term exposure to lemon EO can induce significant, at times sex-specific, changes in neuronal circuits involved in anxiety and pain.     

Substantial decrease of psychiatric comorbidity in chronic alcoholics upon integrated outpatient treatment - results of a prospective study

It is far from clear how comorbidity changes during alcoholism treatment. This study investigates: (1) the course of comorbid Axis I disorders in chronic alcoholics over 2 years of controlled abstinence in the outpatient long-term intensive therapy for alcoholics (OLITA) and (2) the effect of comorbid Axis I and II disorders in this group of patients on subsequent drinking outcome over a four-year follow-up. This prospective treatment study evaluates psychiatric variables of 89 severely affected chronic alcohol dependent patients on admission (t₁), month 6 (t₂), 12 (t₃) and 24 (t₄). Drinking outcomes have been analyzed from 1998 to 2002. On admission, 61.8% of the patients met criteria for a comorbid Axis I disorder, 63.2% for a comorbid personality disorder. Axis I disorders remit from t₁ (59.0% ill), t₂ (38.5%), t₃ (28.2%) to t₄ (12.8%) (p<0.0001). Anxiety disorders remit more slowly from t₁ (43.6%) to t₃ (20.5%, p=0.0086), whereas mood disorders remit early between t₁ (23.1%) and t₂ (5.1%, p=0.0387) with a slight transient increase at t₃ (10.3%). During the four-year follow-up, the cumulative probability of not having relapsed amounts to 0.59. Two predictors have a strong negative impact on abstinence probability: number of inpatient detoxifications (p=0.0013) and personality disorders (p=0.0106). The present study demonstrates a striking remission of comorbid Axis I disorders upon abstinence during comprehensive long-term outpatient alcoholism treatment. The presence of an Axis II rather than an Axis I disorder on admission strongly predicts drinking outcome over a four-year follow-up.     

EPIC-Italy cohorts and multipurpose national surveys. A comparison of some socio-demographic and life-style characteristics

BACKGROUND: EPIC-Italy cohort study recruited subjects who voluntarily accepted to participate in the project. From the self-selected bases of the population sample, some bias could derive in the data interpretation when risk estimation for cancer disease related to life-style factors is the principal concern. Knowledge of the bias related to self-selected sampling is important for better directing the interpretation of the EPIC-Italy study results. METHODS: We investigated the characteristics of volunteer subjects recruited in the EPIC-Italy cohorts and compared them with those of the randomly selected subjects recruited in the Multipurpose ISTAT Surveys realized in the same period (1993-1998) in which the EPIC-cohorts were recruited. RESULTS: We found some differences, and in particular a different attitude towards cigarettes smoking and wine consumption, between the EPIC cohort and the Multipurpose ISTAT Surveys, as well as among geographical areas within the EPIC cohort. CONCLUSIONS: The uneven distribution of some characteristics suggests that the self-selected subjects were characterized by an overall lower consumption of wine and cigarette smoking even when the educational level was considered. This could suggest a generally more healthy life-style among subjects recruited on a volountary bases.     

Association between social class and food consumption in the Italian EPIC population

AIMS AND BACKGROUND: The objectives of the present study were to validate the social stratification variables adopted by the European Prospective Investigation into Cancer and Nutrition (EPIC) by comparing them with data from another independent source and to evaluate the geographic and social distribution of eating habits in the Italian EPIC population. METHODS: The validation of the socioeconomic data collected by the EPIC study was performed with the Turin Longitudinal Study as gold standard and using Cohen's kappa statistics to evaluate the concordance between the studies. We then analyzed food groups based on the consumption of meat and fats, carbohydrates, sweets and alcohol, and on an index of the Mediterranean diet. The standardized scores for each food group were subdivided into quartiles, which were used to compare persons in the extreme quartiles. Analysis of the differences in eating habits by center and by educational level was conducted separately for men and women, calculating the prevalence rate ratios and controlling for age, area of birth and body mass index. RESULTS: Concordance between the two data sources was high for educational level and low for the social-class index based on occupation. Most of the eating habits considered to be potentially harmful (high consumption of meat or fats and alcohol and low consumption of olive oil and fish) were more frequent in Northern than in Southern Italy. These habits were inversely correlated with educational level, especially in the South. CONCLUSIONS: A significant improvement in health could be obtained in the Italian population if culturally and socioeconomically disadvantaged individuals were to abandon their diet rich in meat and fats, as done by more advantaged persons. In the absence of preventive interventions specifically addressed to disadvantaged groups, it is likely that social inequalities in mortality and morbidity will increase.