5-Piperazinylalkyl-2(3H)-oxazolones with neuroleptic activity

A series of new 4-aryl-5-[omega-(4-aryl-1-piperazinyl)alkyl]-2(3H)- oxazolones was synthesized and tested for neuroleptic activity in mice and rats. Several compounds exhibited interesting neuroleptic activity with very low liability to the extrapyramidal side effects. In particular the activity of 4-(4-fluorophenyl)-5-[2-[4-(3,5-dichlorophenyl)-1- piperazinyl]ethyl]-2(3H)-oxazolone (14) was greater than that of butropipazone and fluanisone, while of the same order of that of chlorpromazine; however, the product showed a longer lasting activity and minor ability to produce catalepsy as compared with the reference drugs.     

Treatment of Paget's disease of bone with intravenous 4-amino-1-hydroxybutylidene-1,1-bisphosphonate

Summary 4-amino-1-hydroxybutylidene-1,1-bis-phosphonate (AHButBP) was given intravenously (2.5–25 mg/day for 4 days) to 14 patients with Paget's disease of bone, five of whom had been treated with dichloromethylidene bisphosphonate (Cl₂MBP) 32 months earlier. In the nine patients who had not been treated previously with bisphosphonates, the short course of AHButBP induced a suppression of serum alkaline phosphatase and urinary hydroxyproline values down to 30% of initial values. The biochemical suppression of the disease was sustained for 2–18 months and the time to relapse did correlate to the logarithm of the dose (P<0.001). In the five patients previously treated for Paget's disease, an apparent resistence to treatment with AHButBP was observed. However, in these patients both serum alkaline phosphatase and urinary hydroxyproline fell to or even below the nadir values which had previously been achieved with Cl₂MBP, irrespective of the degree of relapse. Thus the degree of suppression of Paget's disease of bone, achievable after treatment with bisphosphonates, seems to be constant for each patient, such that normal levels of serum alkaline phosphatase and urinary hydroxyproline cannot usually be attained in patients with extremely active disease.     

Quantitative Characterization of Epicardial Wave Fronts During Regional Ischemia and Elevated Extracellular Potassium Ion Concentration

This study applied zero-delay wave number spectral estimation as a means of quantifying the changes in activation and recovery sequences of propagating plane waves on the epicardial surface of in situ porcine hearts during regional hyperkalemia and ischemia. Unipolar electrograms (104) were recorded from the left ventricular surface of nine hearts using a plaque electrode array with 1 mm spatial sampling intervals. The objectives were (1) to define a set of parameters capable of quantifying the spatial and temporal changes in measured extracellular potentials associated with localized ischemia prior to the onset of conduction block; (2) to elevate regional levels of extracellular potassium ion concentration and quantify potential changes due to this known physiologic manipulation; and (3) to use quantitative parameters to make statistical comparisons in order to distinguish wave fronts during normal, ischemic and hyperkalemic conditions. Results showed that the parameters of wave number and average temporal frequency and the associated power, as determined from the wave number spectrum, provided statistically significant (p < 0.05) quantification of changes in wave front features during normal and ischemic or hyperkalemic conditions. The results were consistent with results obtained from conventional time–space domain methods like isochronal mapping and electrograms, with the advantage of a quantitative result enabling simple comparisons and trend analysis for large numbers of heart beats. © 1998 Biomedical Engineering Society. PAC98: 8759Wc, 8722Fy, 8780+s     

Anti-Pseudomonas aeruginosa antibodies and lung disease in cystic fibrosis

The aim of our study was to diagnose and to control three aspects of the evolution of lung disease in CF: the absence of infection, the intermittent colonization and chronic infection by Pseudomonas aeruginosa. Therefore a study of anti-pseudomonas antibodies (Ab) (anti-protease, anti-elastin and antihexo-toxin A) for diagnosis and follow-up of CF patients was considered. Moreover, we related the presence of Ab to the sputum culture, to FEV1, to patient age and to genotype. Tbe Ab were dosed in 121 patients by quantitative ELISA method. Values < 1: 500 were considered negative, values> 1: 500 and < 1:1250 borderline, and > 1:1250 positive. 16.5% of patients did not have Ab, 17% had borderline values and 69.5% had positive values. All the patients with negative Ab had negative sputum culture; 47% of patients with borderline values had at least one positive culture while 53% were negative. 87% of patients with positive values had chronic colonization, 13% intermittent colonization. The increase in the Ab rate is statistically related to a more severe lung disease (p < 0.013). The presence of a severe mutation (?F 508) is related to positive values of Ab. Evaluation of anti-Pseudomonas aeruginosa is an important tool for diagnosis and follow-up of CF lung disease     

Serious childhood respiratory infections and asthma in adult life. A population based study. ECRHS Italy. European Community Respiratory Health Survey.

BACKGROUND: A number of epidemiologic studies have tried to establish whether respiratory tract infections in early childhood cause obstructive pulmonary disease in adult life. OBJECTIVE: To determine whether reported serious respiratory infection before the age of 5 years (SRI) is a significant risk factor for subsequent development of bronchial asthma and/or bronchial hyperresponsiveness in adults. METHODS: We investigated a random population sample of 1,104 subjects (aged 20 to 40 years), participating in the European Respiratory Health Survey in Italy. Bronchial response to methacholine and answers to a standardized questionnaire were analyzed. RESULTS: The prevalence of SRI (ie, a positive response to the question "Have you ever had a serious respiratory infection before the age of 5 years?") was significantly higher in the subjects with a positive family history of allergic diseases than in those with a negative one (O.R. 1.89; 95% C.I. 1.24 to 2.87, P < .01). No relationship was found between SRI and current adult asthma; however, asthma in the past was found in 20.5% of the SRI positive subjects and in 9.1% of SRI negative subjects (O.R. 2.47; 95% C.I. 1.47 to 4.15, P < .05). No difference in the response to methacholine and in FEV1, FEV1/FVC values was found between SRI positive and SRI negative subjects. CONCLUSIONS: We suggest that a positive family history of atopy is associated with a significantly higher prevalence of SRI. Furthermore our results indicate that exposure to SRI is a risk factor for asthma in the past (ie, asthma in childhood and adolescence) but not for adult asthma or for the development of bronchial impairment in adult life.