Dante and cardiology: Physiopathology and clinical features of cardiovascular diseases in the Middle Ages.

Ancient non-medical texts can unexpectedly provide useful information on the development of knowledge about the heart and its diseases throughout history. The 750th anniversary of the birth of the Italian poet Dante Alighieri (1265-1321) provides a timely opportunity to analyze medical references in his works, in particular, focusing on literary descriptions that may be attributed to cardiovascular disorders. Dante's high level of medical knowledge, probably derived from his academic studies, is testified by his affiliation to the Florentine Guild of physicians and pharmacists. In all his works, the poet shows a deep interest for the heart. However, his anatomical and physiological knowledge of the circulatory system appears to be poor, probably due to it being based on theories and concepts brought forth by Aristotle and Galen, which were taught in medieval universities. Despite this, accurate descriptions of some symptoms (emotional syncope, orthopnea, dyspnea on exertion) and signs (ascites, paleness), which may be attributed to cardiovascular disorders, can be easily found in Dante's works, particularly in his masterpiece, the Divine Comedy. The literary and historical analysis of cardiovascular signs and symptoms allows us to assume that clinical features due to alterations of heart function were probably known by medieval physicians, but their etiology and pathophysiological mechanisms were not completely understood in that period. Historians of cardiology and clinicians should consider analysis of non-medical texts (including poetry) as an opportunity to better investigate the evolution of their discipline throughout the ages.

Helminth community structure of the Mediterranean gull (Ichthyaetus melanocephalus) in Southern Italy.

The helminth community of the Mediterranean gull (Ichthyaetus melanocephalus) from the Calabria region in southern Italy was examined. Ten species of helminths, including 2 cestodes (Alcataenia larina and Tetrabothrius cylindraceus), 4 digeneans ( Aporchis massiliensis , Brachylaima fuscatum, Cardiocephaloides longicollis, and Ornithobilharzia canaliculata), and 4 nematodes (Eucoleus contortus, Capillaria sp., Cosmocephalus obvelatus, and Paracuaria adunca), were found. The Mediterranean gull represents new host records for A. larina, A. massiliensis, B. fuscatum, and E. contortus; all species, except C. longicollis and O. canaliculata, constitute new locality records. The gastrointestinal helminth community of I. melanocephalus consisted of 9 species but, at the infracommunity level, species richness, diversity, and total helminth abundance are among the lowest reported from any gull species. Two cestode species accounted for 81% of all helminth specimens found.

Bronchodilator effect of an inhaled combination therapy with salmeterol + fluticasone and formoterol + budesonide in patients with COPD.

In the present trial, we compared the broncholytic efficacy of the combination therapy with 50 microg salmeterol + 250 microg fluticasone and 12 microg formoterol + 400 microg budesonide, both in a single inhaler device, in 16 patients with moderate-to-severe COPD. The study was performed using a single-blind crossover randomized study. Lung function, pulse oximetry (SpO2) and heart rate were monitored before and 15, 30, 60, 120, 180, 240, 300, 360, 480, 600, and 720 min after bronchodilator inhalation. Both combinations were effective in reducing airflow obstruction. FEV1 AUC(0-12 h) was 2.83 l (95% CI: 2.13-3.54) after salmeterol/fluticasone and 2.57 l (95% CI: 1.97-3.2) after formoterol/budesonide. Formoterol/budesonide elicited the mean maximum improvement in FEV1 above baseline after 120 min (0.29 l; 95% CI: 0.21-0.37) and salmeterol/fluticasone after 300 min (0.32 l; 95% CI: 0.23-0.41). At 720 min, the increase in FEV1 over baseline values was 0.10 l (95% CI: 0.07-0.12) after salmeterol/fluticasone and 0.10 l (95% CI: 0.07-0.13) after formoterol/budesonide. The mean peak increase in heart rate occurred 300 min after formoterol/budesonide (1.5 b/min; 95% CI--2.3 to 5.3) and 360 min after salmeterol/fluticasone (2.6 b/min; 95% CI--1.9 to 7.0). SpO2 did not change. All differences between salmeterol/fluticasone and formoterol/budesonide were not significant (P > 0.05) except those in FEV1 at 120 and 360 min. The results indicate that an inhaled combination therapy with a long-acting beta2-agonist and an inhaled corticosteroid appears to be effective in improving airway limitation after acute administration in patients suffering from COPD.

Bronchodilation test in COPD: effect of inspiratory manoeuvre preceding forced expiration.

The effects of an inspiratory manoeuvre preceding forced expiration on functional tests performed under routine conditions before and after inhalation of a bronchodilator drug (salbutamol) were assessed on 150 consecutive chronic obstructive pulmonary disease outpatients. The patients performed forced vital capacity manoeuvres either immediately after a rapid inspiration (manoeuvre no. 1) or after a slow inspiration with a 4-6 s pause (manoeuvre no. 2). Under baseline conditions, forced expiratory volume in one second (FEV1) values were 8% (% control) larger with manoeuvre no. 1 than no. 2. FEV1 values increased with salbutamol administration by approximately 8% and were, on average, still 7% larger with manoeuvre no. 1 than no. 2. The incidence of reversibility, assessed according to American Thoracic Society criteria, was 76% when manoeuvre no. 2 was selected to represent baseline conditions and manoeuvre no. 1 was chosen to represent the effects of bronchodilator administration, whereas the lowest incidence (2%) was found when manoeuvre no. 1 was selected to represent baseline conditions and manoeuvre no. 2 was chosen to represent the effects of bronchodilator administration. These results indicate that the time dependence of the forced vital capacity manoeuvre has an important impact on the assessment of routine lung function in a clinical setting and supports the notion that the time course of the inspiration preceding the forced vital capacity manoeuvre should be standardised.

Addition of an extra dose of salmeterol Diskus to conventional dose of salmeterol Diskus in patients with COPD.

Patients experiencing dyspnoea can request an additional dose of salmeterol during the dose interval for the control of their symptoms, although under treatment with salmeterol. In this study we have explored the effects on respiratory function of an additive dose of salmeterol Diskus in 15 chronic obstructive pulmonary disease (COPD) patients in regular treatment with a conventional dose of 50 microg salmeterol. On two different days, patients inhaled 50 microg Diskus. After 240 min, they inhaled additional 50 microg salmeterol Diskus (salmeterol arm) or placebo Diskus (placebo arm). Lung function was controlled before first drug administration and 0.5, 1, 2, 3, 4, 4.5, 6, 8, 10, and 12 h thereafter. The mean (95% CI) peak increase in FEV1 from baseline was reached after 4 h in the salmeterol arm (0.174 L; 0.144-0204) and after 5 h (0.141 L; 0.115-0.168) inthe placebo arm; after 12 h, the mean (95% Cl) increase in FEV1 from basal values was still 0.149 L (0.119-0.179) in salmeterol arm, but only 0.041 L (0.017-0.064) in placebo arm. The mean (95% CI) FEV1 AUC0-12h for all patients were 2.01 (1.72-2.30) L when salmeterol was added and 1.30 (1.03-1.58) L when placebo was inhaled. The difference (mean; 95% CI) between the FEV1 AUC0-12h of the two arms (0.71 L; 0.47-0.95) was statistically significant (P<0.0001), although the difference (mean; 95% CI) between the FEV1 AUC0-4h of the two treatments (0.08 L; -0.02-0.18) was notstatistically significant (P=0.126). The addition of an extra dose of salmeterol did not significantly increase the heart rate or decrease the SpO2. This study suggests that the addition of an extra dose of salmeterol does not give room for further increase in peak FEV1, but the effect of adding salmeterol to salmeterol is largely additive when considering the duration of action and safe.

Bronchodilating effect of oxitropium bromide in heart disease patients with exacerbations of COPD: double-blind, randomized, controlled study.

Anti-cholinergic agents are considered the bronchodilator therapy of first-choice in the treatment of patients with stable chronic obstructive pulmonary disease (COPD) associated with heart disease since they may be as effective or more effective than inhaled beta2-agonists and, moreover, they do not interact with cardiac beta-adrenoceptors. The aim of our study was to evaluate the bronchodilator activity of oxitropium bromide in outpatients suffering from exacerbations of COPD associated with heart diseases (ischaemic heart disease and/or arrhythmias). We recruited 50 consecutive outpatients (33 males and 17 females, mean age 68.6 years, 15 current smokers and 35 ex-smokers). Each patient performed body plethismography in basal condition and 30 min after inhalation of 200 microg metered dose inhaler (MDI) oxitropium bromide administered by a device (Fluspacer). FEV1, FVC, MMEF25-75, sRaw and tRaw were evaluated. Thirty minutes after 200 microg oxitropium bromide administration, we observed a significant improvement in FEV1 11.6% +/- 1 (mean +/- SEM) (P<0.01); FVC, MMEF25-75 sRaw variation was respectively: 9.2% +/- 0.6, 31.4 +/- 2.9, -19.9 +/- 1.1. Placebo did not significantly change pulmonary function. Our data suggest that oxitropium bromide bronchodilator activity is effective in exacerbations of COPD.

Two-hybrid selection assay to identify proteins interacting with polymerase II transcription factors and regulators.

The RNA polymerase III-based two-hybrid system has been developed to detect interactions between proteins such as RNA polymerase II transcription factors and regulators that cannot be studied by the original RNA polymerase II two-hybrid system. This novel method appears to be most useful for a refined analysis of already known protein-protein interactions. However, the application of this system in library screenings has been impaired by the lack of a suitable assay for the selection of the activated pol III reporter gene in yeast. Here, we describe a novel selection assay for the pol III-based two-hybrid system that makes it readily usable for screening expression libraries to search for interacting partners. Our system utilizes a temperature-sensitive (ts) U6 snRNA, which is synthesized by RNA polymerase III from a mutated SNR6 gene in yeast. In this ts strain, interactions between hybrid proteins activate an artificial pol III reporter construct (UASG-SNR6), which controls expression of wild-type U6 snRNA. This wild-type U6 snRNA can suppress the ts phenotype and allow growth at the nonpermissive temperature of 37 degrees C, thus providing a positive selection system for interacting proteins.

Atopy prevalence and spirometric performance in asymptomatic schoolchildren exposed to air pollution.

The association between respiratory disease and high levels of air pollution is well known. The most common risk factors associated with lung function decrease are air-borne particulates, ozone (O3), nitrogen dioxide (NO2) and sulphur dioxide (SO2). The aim of our study was to evaluate any difference in the prevalence of atopy and any possible early impairment in lung function in two groups of children exposed to different levels of air pollution. We studied 220 children in two cities in northern Italy: Milan (107 children), considered a metropolitan area with a high level of air pollution, and Erba (113 children), a small town, close to Lake Como, considered a rural area with a low level of air pollution. All subjects underwent respiratory function tests and skin-prick tests for the main inhalatory allergens. Parents were requested to fill in a questionnaire about parents' smoking habits and subjective evaluation of local motor traffic intensity. Aerobiological surveys showed a significantly higher grass pollen concentration in Erba than in Milan in the study year and in the three previous years. Schoolchildren in Milan and Erba showed similar pulmonary function results, except for forced expiratory flow at 75% of forced vital capacity (FEF75) values that, while within the range of normality, were significantly lower in Milan than in Erba. A high incidence of atopy was evident in both groups: 45% among the children living in Erba and 35% among those in Milan; skin-prick-test positivity for grass-pollen was statistically more frequent in Erba than in Milan. No evidence of a link between atopy and FEF75 reduction emerged, nor between FEF75 reduction and exposure to passive smoke. The association between FEF75 reduction and chronic high levels of air pollution is appealing, but further confirmation studies are necessary.

[Alcohol, drugs, pharmacologic agents, and street safety]. / Alcol, droga, farmaci e sicurezza stradale.

Deaths due to road accidents during weekends have become a worrying phenomenon in Italy. With the aim of highlighting the role of psychotropic substances (alcohol, drugs of abuse) in causing road accidents, a survey based on clinical and chemico-toxicological analyses has been carried out on car drivers in the Veneto region during night weekends since 1994. Rapid clinical screening was carried out on 7952 drivers. 1399 of these, suspected to be under the influence of psychotropic substances, were subjected to complete clinical and toxicological ascertainment involving the following procedures: a) anamnesis, aiming at evidence of possible current or past use of psychotropic substances; b) objective clinical examination, aiming at finding evidence of recent (signs of acute or chronic intoxication) or past use (signs of withdrawal or associated organic pathologies) of psychotropic substances; c) double sampling of blood and urine and chemico-toxicological analysis using immunochemical, GC-HS and GC/MS-SIM techniques. As well as many data of social and behavioural interest, processing of results demonstrated that: a) 56.7% of the drivers examined had consumed alcoholic beverages; b) 30.4% had BACs higher than the threshold permitted in Italy (80 mg/100 ml); c) 15.7% of drivers were found to be under the influence of drugs of abuse or psychoactive drugs; d) the most frequently found substances were (in order): cannabinoids, stimulants (cocaine, amphetamines), opiates.

Psychological issues in the treatment of asthmatic patients.

Recently published research contends that anxiety and depression are more common in asthmatic patients than in the general population. Particular psychological profiles could even be a risk factor contributing to deaths caused by asthma. The purpose of our research was to evaluate the anxiety and depression level in a population of 80 asthmatic patients who were treated in our department, and to judge whether data collected on psychological profiles of these asthmatic patients can be of any significance when dealing with their pathology. The study consisted of 40 patients suffering from chronic viral hepatitis B or C, and 40 healthy subjects who served as a control group. Both sets of patients were homogeneous with regard to sex, age and education. All subjects were tested for anxiety and depression levels with the S.T.A.I. and Zung questionnaires. A structured questionnaire was employed to assess the daily approach to living with the disease only in asthmatic patients. The anxiety and depression levels were noticeably higher in asthmatic patients than in patients with chronic liver disease and healthy subjects. In particular, 34 asthmatic patients scored higher than the S.T.A.I. cut-off (40/80) and 27 attained the same results in the Zung questionnaire. Results from the asthmatic population and healthy subjects illustrated that women had a higher incidence of anxiety and depression compared to men, although no statistically significant relationship between sex and questionnaire results was apparent in patients with liver disease. In the year before assessment, hospitalization and emergency treatment due to asthmatic exacerbation was correlated in females with a high incidence of anxiety. Additionally, the asthmatic population's level of education is significantly related to the incidence of anxiety and depression. With higher education, incidence of depression and anxiety decreased. This result was not apparent in control groups. The results of our study were: (1) we confirmed that asthmatic pathology is associated with an increase in incidence of anxiety and depression, whose presence and seriousness should be taken into consideration in therapeutic programmes when dealing with a patient; (2) we indicated that a specific approach towards therapy is crucial when dealing with an asthmatic patient; (3) we suggested how important it is to identify categories of patients that require more care because of their psychological profile. These findings should provide for the optimal use of informational resources with important applications for educational programmes and the future treatment of the asthmatic population.

Proficiency testing for psychoactive substances in Italy.

This paper describes the general design and main results of the Italian proficiency testing program for the analysis of psychoactive substances in urine, a long-term initiative created in 1995 on an educational basis and characterized by an innovative internet-based service for data exchange between laboratories and the organizing body. Batches of six urine samples, validated by reference laboratories, are sent every 3 months to participating laboratories, which may choose which classes of substances to test from those planned by the program panel and, within those classes, which type of analytical commitment to work on: identification of just one class (Option 1), identification of single substances (Option 2), or identification and quantification of single substances (Option 3). Comprehensive periodical reports and annual reports are provided to participants with evaluation of their performance and an annual workshop is organized to discuss technical-scientific topics related to clinical, forensic and analytical toxicology. About 200 laboratories currently participate in the program and a total of 67,059 analyses have been carried out since 1995. The mean percentage of correct results was 96.8%, with a yearly improvement of about 0.4%. The best average false positive and false negative rates were obtained for methadone (0.2% and 2.1% respectively) and cocaine (0.3% and 2.2%). The worst average false positive rates were obtained for amphetamines and opiates (3.2% and 5.0%) and worst average false negative rates for amphetamines, barbiturates and cannabinoids (17.4%, 30.7% and 19.9%).

Drugs-of-abuse testing in urine: statistical approach and experimental comparison of immunochemical and chromatographic techniques.

This study deals with the experimental and statistical comparison of six immunochemical techniques, including noninstrumental on-site and instrumental formats (EIA-EMIT and EZ-SCREEN; FPIA-ADx; RIA-Coat-A-Count; LI-Abuscreen ONTRAK; CBI-Triage), and three chromatographic techniques (TLC-Toxi-Lab; HPLC; HPLC-REMEDi drug profiling system), using GC-MS as a reference technique for analyzing amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates in the urine of various kinds of drug users. The study reports (a) the values of sensitivity, specificity, false-positive rates, and false-negative rates of each technique; (b) the results of bayesian statistical analysis, which are based on prevalence values of the samples examined and expressed as positive and negative predictive values and cumulative predictive values for each single technique and for combinations of paired immunochemical and chromatographic techniques; and (c) the results of a rough classification of the various degrees of predictability of these techniques. Lastly, this study proposes a decision-making process for establishing the best combination of analytical techniques for the goals in question, according to the characteristics and facilities of each laboratory.

Therapeutic gamma-hydroxybutyric acid monitoring in plasma and urine by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric (GC-MS) method for the determination of therapeutic levels of gamma-hydroxybutyric acid (GHB) in plasma and urine samples is described. GHB is converted to its lactonic form gamma-butyrolactone (GBL) which is extracted from biological fluids after the addition of the internal standard delta-valerolactone. Final GC-MS analysis is obtained under electron impact selected ion monitoring (SIM) conditions. Mean relative recoveries of GHB from plasma and urine are 75.5% (RSD% = 2.2) and 76.4% (RSD% = 2.4), respectively. The assay is linear over a plasma GHB range of 2-200 micrograms ml-1 (r = 0.999) and a urine GHB range of 2-150 micrograms ml-1 (r = 0.998). Intra- and inter-assay relative standard deviations (n = 5) determined at 10 and 100 micrograms ml-1 are below 5%. The method is simple, specific and accurate, and may be applied for analytical purposes related to pharmacokinetic studies and therapeutic drug monitoring.

Simultaneous identification of amphetamine and its derivatives in urine using HPLC-UV.

An HPLC-UV method for the simultaneous identification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine is described. It includes a rapid extraction procedure of the 4 analogs from urine using Extrelut 3 columns, derivatization with sodium 1,2-naphthoquinone-4-sulphonate (NQS) to obtain highly chromophoric UV-VIS derivatives, and a final HPLC analysis using an ion-pair reversed-phase technique with eluent monitoring at 480 nm. Structural characterization of the derivatives obtained by mass spectrometry is reported. Recoveries of the amphetamines were in the range 80-85% at concentrations of 300 ng/ml. Practical detection limits were 40-60 ng/ml (S/N ratio = 10) for all derivatives. The chromatographic peaks of the NQS derivatized amphetamines are fairly narrow and well resolved. The method is simple, rapid, quite sensitive, and specific for convenient confirmation of preliminary positive results obtained with immunoassays.

Pharmacokinetics of gamma-hydroxybutyric acid in alcohol dependent patients after single and repeated oral doses.

1. The pharmacokinetics of gamma-hydroxybutyric acid (GHB) were studied in 10 alcohol dependent subjects after single and repeated therapeutic oral doses (25 mg kg-1 every 12 h for 7 days). 2. GHB was readily absorbed and rapidly eliminated (tmax = 20-45 min; mean t1/2z 27 +/- 5 s.d. min). Urinary recovery of unchanged GHB was negligible (less than 1% of the dose). gamma-butyrolactone was not detected in either plasma or urine, indicating that lactonization of GHB does not occur in vivo. 3. The multiple-dose regimen resulted neither in accumulation of GHB nor in time-dependent modification of its pharmacokinetics. 4. In five subjects, the data were consistent with nonlinear elimination kinetics of GHB. Administration of a 50 mg kg-1 dose to these subjects resulted in significant increases in dose-normalized AUC, t1/2z and mean residence time. 5. Doubling of the dose also resulted in a significant increase in tmax with little change in Cmax. 6. At the administered doses, GHB did not accumulate in the plasma and caused no serious side effects.

Solid-phase extraction and HPLC-UV confirmation of drugs of abuse in urine.

A series of six liquid chromatographic methods were developed to confirm the presence of six classes of drugs of abuse in urine. The chromatographic separations were performed with a reversed-phase C8 column, except in the case of morphine, which was separated on a normal phase column. Isocratic and gradient elutions, ion pair technique, and UV detection were employed. Sample pretreatment involved the extensive application of solid-phase extractions and liquid-liquid extractions on solid supports. The specificity and sensitivity enabled the confirmation of morphine, benzoylecgonine, THC-COOH, amphetamine, and methamphetamine, six barbiturates, and nine benzodiazepines screened positive by EMIT in urine.

Direct and indirect homogeneous enzyme immunoassay of benzodiazepines in biological fluids and tissues.

The evaluation of new homogeneous enzyme immunoassay (EMIT) for benzodiazepines is described. The assay, although developed for direct analysis in serum, has been used to detect benzodiazepines in other body fluids and tissues; this is accomplished through two processes. The first consists of a previously reported technique of extraction and reconstitution of the original specimen. The second consists of dilution of the original specimen. The assay is compared to a gas chromatographic procedure.