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G Recchia

Publications and source records attributed to G Recchia.

At least 19 recordsLinked to original sources

Pharmacogenetics and pharmacogenomics: are they still promising?

In the last several years pharmacogenetics and pharmacogenomics have attracted the interest of the scientific community and of important pharmaceutical groups. What is the consequence for medicine and for the pharmaceutical industry? What has emerged from this investment, and what can we expect for the future? As with many new technologies, pharmacogenetics and pharmacogenomics were first adapted with much enthusiasm, and then found to require time and experience, together with sustained investment, before they could take their full place in drug discovery and development. The benefits of these technologies are now emerging, however, and they have become essential tools for the pharmaceutical industry.

Animals↗

Rise and fall of asthma-related mortality in Italy and sales of beta2-agonists, 1980-1994.

We performed this study with the aims of describing the trend of asthma-related mortality in Italy between 1980 and 1994, and to evaluate the relationship between sale estimates of beta2-agonists drugs and mortality from asthma. For asthma mortality we used data provided by National Institute of Statistics, for sale estimates of beta2-agonists we used data provided by IMS HEALTH. We calculated the gender specific age-standardized incidence rates of asthma-related deaths for all ages and for age classes. We found that estimates for asthma-related mortality steadily increased between 1980 and 1987 in both sexes, and thereafter decreased. In people, aged between 34 and 64 and over 64, death rates in males were significantly higher than in females while the rates in those aged less than 34, were mostly similar in both gender. The overall exposure to beta2-agonists (alone and in combination) increased from 1980 to 1990, remained stable between 1990 and 1993, and increased steeply in 1994. We conclude that asthma-related death rates have declined since the mid-1980's. This decline has been more pronounced in males and in the older ages, while the rates in younger patients of both genders have remained nearly unchanged. Our data do not substantiate the hypothesis of an increased risk of asthma-related mortality associated to the use of inhaled beta2-agonists in general nor fenoterol or salbutamol in particular.

Administration, Inhalation↗

An epidemiological study to assess migraine prevalence in a sample of Italian population presenting to their GPs.

This multicentre, observational, cross-sectional study was conducted to determine migraine prevalence in a sample of population presenting to their GPs. The study covered all the patients who visited the GPs practice, for any reason, on 5 consecutive days of 2 different weeks. A total of 71,588 patients were interviewed by 902 GPs. The prevalence of migraine in this sample was 11.6%.

Adolescent↗

Measuring quality of life in dyspeptic patients: development and validation of a new specific health status questionnaire: final report from the Italian QPD project involving 4000 patients.

OBJECTIVE: Despite the fact that gastrointestinal disorders represent one of the most common reasons for medical consultations, formal assessment of patients' health-related quality of life (HRQOL) has been carried out only in a few studies, and in most cases generic questionnaires have been adopted. Because the specific issue of living with dyspeptic problems has been addressed in very few cases and no questionnaire has been shown to be appropriate for the Italian setting, a prospective project was launched to develop a specific HRQOL questionnaire for dyspepsia sufferers tailored to Italian patients but also appropriate in other cultural settings. METHODS: The project consisted in a 3-yr, three-phase survey, in which different versions of the quality of life in peptic disease questionnaire (QPD) were developed through expert and patient focus groups and empiric field studies and then administered to patients recruited in five multicenter studies. Standard psychometric techniques were used to evaluate the validity, reliability, responsiveness, and patient acceptability of the QPD. RESULTS: Three different versions of the QPD questionnaire were self-administered to more than 4000 patients. The final 30-item version, measuring three health concepts related to dyspeptic disease (anxiety induced by pain, social restriction, symptom perception), fulfilled the recommended psychometric criteria in terms of reliability and validity, correlated with health concepts measured with a well-known independent generic HRQOL instrument (the SF-36 Health Survey questionnaire) and was relatively invariant to diagnosis and sociodemographic variables; it also correlated with a measure of gastric pain frequency and was able to detect meaningful differences over time. CONCLUSIONS: Although further validation studies in different cultural and linguistic settings are mandatory before any firm conclusions can be drawn regarding the cross-cultural validity of the QPD, the data obtained provide evidence of the psychometric validity and robustness of the questionnaire when used in a fairly large, well-characterized population of Italian dyspeptic patients.

Adult↗

The epidemiology of migraine: a retrospective study in Italian emergency departments.

This study was conducted to measure the frequency of contact with emergency departments in Italy because of migraine, and to compare the initial diagnosi s of headache with the diagnosis after application of the International Headache Society (IHS) criteria. A retrospective observational method was used, consisting of an analysis of the records of patients admitted to nine Italian emergency departments during different 4-month periods in 1994. Comparison of the initial diagnosis with the diagnosis after application of the IHS diagnostic criteria was performed. More than 31 million emergency department contacts were reported in Italy during 1994. In the same year, 543 630 patients visited the nine emergency departments enrolled in the study, with 169 569 of these contacts occurring in the 4-month period analyzed in the study. We excluded from the analysis all cases of secondary headache fully recognized at the emergency department admission (ie, traumas, intracranial pathology, systemic diseases). The total number of patients included in our analysis was 1043 (0.6%). The 934 patients who could be fully evaluated were initially classified as having migraine; cluster headache; headache not otherwise specified; or diagnosed in the emergency department as suffering from headache, but reclassified by other departments as suffering from a different disease. After retrospective application of the IHS classification, the diagnostic distribution was modified, revealing that 18% of patients with migraine and 5% with cluster headaches had previously been classified as having headache not otherwise specified; a further 6% of cases with migraine and 0.4% of patients with cluster headache had previously been classified as having secondary headaches. The diagnosis of headache not otherwise specified was made with notable frequency, indicating the limits of emergency department logs and the difficulty in carrying out a retrospective analysis and reassessment of diagnosis. The majority (88%) of patients assessed had not taken drugs for headache in the 48 hours before the emergency department contact, suggesting that in Italy emergency departments are used instead of a visit to the general practitioner. Nonsteroidal anti-inflammatory drugs were the most frequently prescribed drugs in the emergency departments for this group of diagnoses. The research revealed, on the one hand, that headache is a numerically significant phenomenon in the emergency department setting and, on the other, the need to apply prospective designs to this kind of survey.

Cluster Headache↗

[Development and validation of QPD 32, a specific questionnaire for measuring the quality of life of patients with peptic ulcer].

Drugs need to be evaluated both in terms of efficacy, safety and regarding the patient's perception of his own health status. For these reasons, sensible, reliable and patient-oriented instruments are needed, besides the methodologies for evaluation of drug efficacy and safety. Such instruments substantially evaluate Health related Quality of Life (HrQoL). Concerning gastric acid hypersecretion few papers are available, based on HrQoL questionnaires, both general and specific. A research project led us to develop through patients and physicians involvement, a specific instrument to evaluate HrQoL as to the various aspects of the peptic disease. The project started in 1993 through a series of 4 focus groups with gastroenterologists and patients, followed by the preparation of a questionnaire named QPD48. Such instrument was psychometrically validated through a study named Herqules 1, involving 176 gastroenterologists and 1774 patients. The psychometric analysis on QPD48 led to the re-issue of a questionnaire named QPD32 with Chronbach's alfa equal to 0.91, based on 3 factor-referenced subscales evaluating pain, induced anxiety, constrained daily living and awareness of symptoms and agents. Concerning the concurrent validity a one-way analysis of variance showed highly significant differences associated with attack frequency with substantial effect sizes ranging from 0.46 to 1.27 of a standard deviation in the full scale. QPD 32 is patent protected and will be used in clinical trials.

Adult↗

New anxiolytics in development.

Benzodiazepines (BDZ), the most popular drug of choice for treating anxiety disorders, present side-effects such as sedation, muscular disorders, abuse liability and synergistic effect with alcohol and CNS depressant drugs. At present, pharmacological research is focusing to find anxiolytic drugs as efficacious as benzodiazepines but without side-effects. This review reports the status of the pharmaceutical research and development on novel drugs for the treatment of anxiety disorders. A close analysis of the items selected by the N5C "Pharmaprojects" search (anxiolytic class) yielded the following classification: A) Drugs interacting with the GABA-A receptor complex, which includes BDZ-like drugs, partial BDZ agonists (beta-carbolines) and drugs interacting with the GABA-A complex through an as yet unidentified mechanism (15 compounds), B) Drugs acting as CCK-B antagonists (5 compounds), C) Drugs interacting with serotonergic function (30 compounds) subdivided into: (i) agonists at the 5-HT1A receptor, (ii) antagonists at the 5-HT2 receptor, and (iii) antagonists at the 5-HT3 receptor; D) Drugs with other mechanisms (22 compounds). Based on these results, it is not possible to identify a common mechanism through which the selected drugs under development exert their anxiolytic effect. Therefore, it appears that different biological mechanisms are specifically involved in the different anxiety disorders.

Anti-Anxiety Agents↗

[Bacterial infections. Progress and new prospects in chemo-antibiotic therapy].

During the last 10 years, a very large number of molecules with antibacterial activity has been developed by pharmaceutic industry. The principal objectives of pharmacological research are to obtain ever wider spectra of activity and increased antibacterial action in order to combat "emerging" agents and those resistant to traditional treatment, as well as longer acting drugs so as to improve patient compliance. These objectives might be attained by the molecules now in the phase of clinical trial, especially by the new injectable or oral cephalosporins and new fluoroquinolones.

4-Quinolones↗

Efficacy and safety of lacidipine, a new long-lasting calcium antagonist, in elderly hypertensive patients.

Elderly patients are becoming a greater proportion of the hypertensive population. In addition, they may respond differently to drugs, both pharmacodynamically and pharmacokinetically. Therefore, approximately 25% of the patients treated with lacidipine in early studies were over 65 years old. In three double-blind, parallel-group comparative trials, 118 elderly hypertensive patients were treated with lacidipine or comparators, either atenolol, nifedipine SR, or hydrochlorothiazide (HCTZ). Lacidipine was at least as effective in lowering blood pressure as the comparators, as well tolerated as nifedipine SR (but with a significantly lower incidence of edema) and HCTZ, and better tolerated than atenolol. In a double-blind, placebo-controlled, parallel-group, dose-response study of 131 elderly hypertensive patients randomized to receive either lacidipine or placebo, lacidipine significantly reduced the diastolic blood pressure compared with placebo. In the long-term evaluation, more patients required titration with 2 mg of lacidipine than with 4 mg. These results suggest that 4 mg once daily is an effective and well-tolerated antihypertensive treatment in the elderly and, as with the general adult population, represents the optimal long-term maintenance dose.

Aged↗

Azapsoralens: new potential photochemotherapeutic agents for psoriasis.

New bioisoters of psoralen, obtained by replacing carbon 8 of the central benzene ring with a nitrogen, were studied from the photochemical, photobiological and phototherapeutic points of view. In particular, 4,4'-, 4',5'-dimetyl, 4,4',5'-trimethyl and 3,4,4',5'-tetramethylazapsoralen were studied. The crystal and molecular structure of 4,4',5'-trimethylazapsoralen, obtained by X ray diffraction, was also reported. Like psoralen, these compounds form a molecular complex with DNA, undergoing intercalation inside the double helix of the macromolecule. When irridiated with long ultraviolet light (365 nm), the intercalated drug photoconjugates covalently to the macromolecule, forming mono- and diadducts. The photobinding rate show the following order of magnitude: 4,4',5'-trimetylazapsoralen (4,4',5'-TMAP) = 3,4,4',5'-tetramethylazapsoralen (3,4,4',5'-TMAP) greater than 4',5'-dimethylazapsoralen (4',5'-DMAP) = 4,4'-dimethylazapsoralen (4,4'-DMAP). The DNA photobinding rate of 8-methoxypsoralen (8-MOP), taken as reference compound, is similar to that of the two dimetylazapsoralens but lower than tri- and tetramethyl derivatives. The ability of azapsoralens to form cross-links in DNA is lower than that of 8-MOP. However, capacity to induce cross-links does not parallel the DNA photobinding rate; it is higher for trimethyl derivate and lower for tetramethylazapsoralen. Azapsoralens show evident antiproliferative activity. The trimethyl derivative is the most active, followed by tetrametyl, both these compounds showing activity slightly higher than that of 8-MOP. The two dimethylderivatives are less active. The mautagenic activity of azapsoralens on E. coli WP2 TM6 is lower than that of 8-MOP in the same conditions. The new compounds do not show any skin phototoxicity on guinea pig skin. On the basis of its DNA photobinding, antiproliferative activity, mutagenicity and lack of skin phototoxicity, 4,4',5'-TMAP was chosen for clinical evaluation. Clinical results obtained by topical treatment of psoriatic plaques reveal evident therapeutic effectiveness and clearing is between good and moderate, although 8-MOP, used as reference compound, is more effective.

Animals↗

[Aging of the population: the 2d demographic revolution].

The extension of the duration of life and the growth of elderly population stimulate the neuropharmacology to research new preparations and consequently to develop new methodic of research. At present a project of research started by Glaxo and coordinated by the Centre for Geriatric and Gerontology of Modena University on "The use of a methodology to evaluate aging population and to investigate the effects of L-Acetylcarnitine in senile deterioration" is in progress. Some aspects of this research, like dimension, experimental method, ways of management, evaluation of findings are new. They were discussed and examined during a meeting held on 22nd and 23rd September 1989, the reports of which are in this volume.

Acetylcarnitine↗

[Clinical development of a drug for brain aging. Current limitations and future prospects].

The clinical development of any drug used in the treatment of brain-ageing, poses many methodological problems regarding the difficulty in defining precisely the pathology, both from the point of view of diagnostic and of terminology, the lack of specific parameters for assessing the therapeutic efficacy and the difficulty of establishing homogeneous trial sample, since the geriatric population is a very heterogeneous whole. The authors, in the light of the research done, state their methodology and give their directives; among them: common training for all the examiners, in order to make execution and classification of the tests extremely homogeneous the drug is evaluated through psychometric tests, which analyze the patient both physically and mentally.

Acetylcarnitine↗

6-Methylangelicins: new monofunctional photochemotherapeutic agents for psoriasis.

The monofunctional furocoumarins, the 6-methylangelicins, were tested for their antiproliferative activity with various animal models and for genotoxicity in micro-organisms and in mammalian cells. The most active compound was 6,4,4'-trimethylangelicin, which showed a high antiproliferative effect and reduced genotoxicity in comparison with 8-methoxypsoralen (8-MOP). Some of these compounds were also tested clinically by topical application on 17 patients with psoriasis. They appeared to be more active than 8-MOP in clearing psoriasis without inducing skin phototoxicity. The methylangelicins also caused skin pigmentation.

Animals↗

Safety profile of ofloxacin in elderly patients.

In clinical trials co-ordinated in Italy by Glaxo S.p.A. from May 1984 to February 1988, 553 patients aged over 65 years (376 men and 177 women), suffering from different infectious diseases (mostly LRTI and UTI), were treated with ofloxacin, a new broad-spectrum quinolone. Of the patients studied, 75% presented one or more concurrent diseases and 72.3% were receiving one or more concurrent therapies. Daily dose of the drug varied, in most cases, between 400 and 800 mg in two oral administrations. In all, 21 adverse events were recorded in 19 patients (3.44%): 13 gastrointestinal events (gastric pain, nausea, vomiting), 3 cutaneous events and 5 others. The severity of the events was judged as mild in 56.3% of the cases and moderate in 43.7%. The treatment was stopped because of adverse events in three patients (0.54%). Abnormal laboratory parameters, probably related to the drug, were observed in four patients. In conclusion, ofloxacin appears to be a very safe drug in the treatment of bacterial infections in elderly patients.

Aged↗

[Hyperparathyroidism in patients having undergone a kidney transplant].

The persistence or onset of hyperparathyroidism following kidney transplant is characterized by an incidence ranging from 2.6 to 70% according to the various statistics available. In a total of 462 kidney transplants performed in our department, hyperparathyroidism was detected in 9 patients. Surgery took the form of parathyroidectomy 8/8 plus autograft in 3 cases, parathyroidectomy 3/4 in 2 cases, 7/8 in 2 cases, and 4/8 in 1 case. Serum calcium values returned to normal in all patients after the operation.

Humans↗