Innovative formulations for the controlled and site-specific delivery of antiinflammatory drugs.

Pharmaceutical technology has introduced a promising pathway in the future of medicine in particular nanotechnological innovations have provided the opportunity to design and develop efficient drug delivery systems able to target and treat several diseases, including those mediated by inflammation. The engineering of drug delivery systems can be used to target tissues involved in the pathology under treatment, to avoid early drug biological environmental degradation and to modulate drug pharmacokinetics. Glucocorticoids and non-steroidal anti-inflammatory drugs are the most commonly prescribed drug categories worldwide for the treatment of disorders associated with inflammation. Although glucocorticoids can be highly effective in treating inflammation, their systemic application is limited due to the high incidence of serious adverse effects, mainly in long-term treatment. Non-steroidal anti-inflammatory drugs are a heterogeneous group of compounds and most of them have unfavorable pharmacokinetics and pharmacodynamics, leading to adverse effects, such as gastrointestinal disorders. Therefore, the need for drug delivery systems for long term administration of anti-inflammatory drugs with a well-controlled release profile is evident. The aim of this review is to assess innovative colloidal drugs carriers, in particular liposomes and nanoparticles, with special focus on site-specific delivery for particularly problematic tissues such as the gastrointestinal tract, joints and eyes.

Probability of early repeat Pap smear in an integrated cervical screening programme.

The integration of routine Pap smear practice based on self-referral into an organized programme based on personal invitation is the recommended approach to cervical cancer screening. In this study, the cytology archive of the integrated cervical screening programme implemented in the Faenza district (northern Italy) was used to compare the population of women responding to invitation with that of self-referred women for the cumulative probability of early (< 36 months) repeat Pap smear after a negative result. Between 1995 and 1998, women aged 25-64 living in five municipalities of the district were targeted by the first round of the programme. Eligible for the study were 2356 women responding to invitation for screening and 2221 women not invited because of self-referral for Pap smear at any other setting. The probability of early repeat Pap smear was estimated by the life table method. Differences were evaluated by the Gehan test. Multivariate determinants were assessed by the Cox regression analysis. At 36 months' follow-up, the cumulative probability of early repeat Pap smear was 44% among self-referred women and 6% among women responding to invitation (relative hazard = 4.8). For self-referred women, the probability was related to age (with a peak at 35-44 years), previous Pap smear history and municipality of residence. Among women responding to invitation, only an inverse association with age was demonstrated. In conclusion, the observed differences in overall probability and determinants of early repeat Pap smear between the two screening populations provided important information on Pap smear usage in the total target population.

Benign breast surgical biopsies: are they always justified?

AIM OF THE STUDY: To evaluate the indications for open surgical biopsy of breast lesions resulting in a benign histologic report. METHODS: A consecutive series of 754 benign breast biopsies was collected from six Italian centers previously participating in a multicenter study on the benign/malignant biopsy ratio. Histologic diagnosis, diagnostic tests performed, final clinical diagnosis and the indication for surgical biopsy were compared. RESULTS: Fibrocystic alterations represented the most frequent histologic type (43.2%), followed by fibroadenomas (34.5%). Atypical hyperplasia, phyllode tumors and cancer-like lesions (radial scar, sclerosing adenosis) accounted for a minority of cases. The diagnostic approach was different among centers, with mammography, ultrasonography or cytology being underused in some of them. Suspicion of cancer was an indication for surgical biopsy in 66.7% of cases. In the remaining cases the final report was negative or benign, but biopsy was advised for growing lesions (11.3%) or for cosmetic (3%) or psychological reasons (8.2%). In 4% of cases surgical biopsy was presumably advised for the concurrent influence of high-risk conditions such as previous breast cancer (0.7%), family history of breast cancer (2%) or contralateral synchronous breast cancer (1.3%). In 6.8% of the cases biopsy was advised elsewhere for unknown reasons. The indications for biopsy differed among centers, with one center having a low rate of suspicious cases (37%) and a high rate of reported "cosmetic" or "psychological" reasons (47%). CONCLUSIONS: Leaving aside differences in diagnostic approach and aggressiveness, two thirds of all lesions were biopsied in order to exclude cancer. The routine use of a more complete diagnostic protocol and/or alternative methods to obtain a histologic diagnosis (e.g. core biopsy) might substantially reduce the need for open surgical biopsy.

Development and validation of a liquid chromatographic method for the determination of related substances in verapamil hydrochloride.

The development of a reversed-phase liquid chromatographic method for the determination of related substances in verapamil hydrochloride is described. The method is based on the use of a simple mobile phase on a specialty base-deactivated reversed-phase column. It enables the resolution of 13 related compounds from the parent drug and from each other. Validation of the method showed it to be reproducible, selective, accurate and linear over the concentration range of analysis with a limit of detection of 0.5 microgram ml-1. The developed method proved to be a real improvement compared with the LC test for chromatographic purity described in the USP monograph for verapamil hydrochloride.

Time trends of benign/malignant breast biopsy ratios a multicenter Italian study.

AIMS AND BACKGROUND: Although they have been decreasing over time due to improved specificity of diagnostic assessment, benign biopsies of the breast are still common. Benign biopsies should be regarded as negative events, due to their economical and psychological cost and their possible negative impact on cosmesis and on further diagnostic evaluation. METHODS: Retrospective data on benign/malignant breast biopsies ratio (B/M) were collected in 9 Italian centers for a period of 10-15 years. The time trend of B/M and its association to age or to single centers was evaluated. RESULTS: Overall 31,001 cases were considered. A strong association of B/M to age was evident (average B/M values were 5.0, 1.3, 0.6, and 0.2 for women aged < 40, 40-49, 50-59, and > 59 years). A significant trend of decreasing B/M over time was observed only for one center. Age standardized B/M was significantly different (P < 0.000001) between centers, ranging between 0.34 and 1.69. Multivariate analysis confirmed an independent significant association of age and center to B/M. CONCLUSIONS: Marked differences in B/M are evident between centers, which cannot be explained by the confounding effect of age or by any apparent difference in the diagnostic protocol. The observed differences are likely ascribed to individual variations in diagnostic aggressivity. A progressive increase of the predictive value of calls for surgical biopsy may be achieved over time and centers with a high B/M should make every effort to optimize their performance. Acceptable (< 40 = 5, 40-49 = 1.5, 50-59 = 0.75, > 59 = 0.3) and desirable (2.5, 0.75, 0.35, 0.15) age specific reference standards for B/M are proposed.