3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot) in advanced prostate cancer: results from an Italian,open, multicenter trial

OBJECTIVES: To determine the endocrine effects, efficacy and tolerability of the 3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot; 'Zoladex' is a trade mark of the AstraZeneca group of companies) in the treatment of patients with advanced prostate cancer. METHODS: Between February 1996 and October 1997, this open, multicentre study enrolled 120 patients with locally advanced (T3/4) or metastatic (N+ or M1) disease, or an increase in prostate-specific antigen (PSA) level after radical prostatectomy. Patients received goserelin acetate 10.8-mg depot every 12 weeks until clinical progression or interruption for adverse events or other reasons. RESULTS: The mean testosterone concentrations were suppressed to the castration range (< or =2 nmol/l) after 4 weeks of treatment and remained suppressed throughout the study. In total, 99/115 (86%) patients had a serum PSA response, and the mean PSA value decreased significantly during treatment (p = 0.006). The mean PSA level at baseline was significantly lower in patients without disease progression compared to those who experienced disease progression (p = 0.0002). Goserelin acetate 10.8-mg depot was well tolerated and there were no injection site reactions. CONCLUSIONS: The goserelin acetate 10.8-mg depot is well tolerated with no injection site reactions. It produces PSA responses and provides reliable suppression of serum testosterone.     

Analogic versus digital mammographic examination a radiological study of mammary microcalcifications on 52 surgical samples

PURPOSE: Digital mammography is known to have lower spatial resolution compared to conventional analogic mammography. The aim of this study was to evaluate whether this physical feature could compromise the perception of microcalcifications in radiological findings. MATERIALS AND METHODS: Fifty-two surgical samples of non-palpable breast lesions with microcalcifications were imaged using both techniques. The images were examined by four different radiologists. Data processing was limited to comparing the number of microcalcifications found on the conventional and digital images, in both standard and magnified modality. The cases were classified into 3 groups according to the number of calcifications demonstrated in the surgical sample: less than 10, 10 to 30, and more than 30. The differences in the count of microcalcifications with the two acquisition modalities were evaluated with the Kappa test. In order to compare the differences we synthesised by percentage those cases exhibiting a larger or lesser number of calcifications. RESULTS: The Kappa test was 0.546 in standard analogic vs standard digital, 0.582 in magnified analogic vs magnified digital, 0.828 in standard analogic vs magnified analogic and 0.492 in standard digital vs magnified digital. The most significant results were observed on comparing the magnifications produced with the two modalities: in 25% of cases, digital magnification detected more calcifications than did traditional magnification. The number of cases where standard digital images allowed the detection of more calcifications than standard analogic images was significant, although less important (17.8%). CONCLUSIONS: The study was able to provide data that confirm the overall equivalence of the two techniques, as far as subtle mammographic findings (such as microcalcifications) are concerned. In particular, as applied to the series we examined, there is a cautious advantage in favour of the digital technique. More clinical studies, on larger series, will be necessary for a further and more thorough comparison of the two techniques, so that the results might be consistently useful in clinical practice.     

c-Cbl is a critical modulator of the Ron tyrosine kinase receptor

Ron, the receptor tyrosine kinase (RTK) for the macrophage stimulating protein (MSP), activates multiple signaling pathways by recruiting several positive regulators to a multifunctional docking site. Here we show that stimulation by MSP also recruits a negative regulator, the c-Cbl ubiquitin ligase, to the multifunctional docking site as well as to a juxtamembrane tyrosine autophosphorylation site. c-Cbl recruitment to these two sites results in polyubiquitylation of Ron molecules, which are subsequently sorted for endocytosis and degradation. Both the phosphotyrosine binding domain of c-Cbl and its RING domain are essential for downregulation of Ron. Although Ron and c-Cbl are found also in physical complexes that include Grb2, these associations are insufficient for productive ubiquitylation of Ron. Our results shed light on the mechanism of receptor desensitization mediated by c-Cbl and its binding partner Grb2.     

Multicentric survey on hygienic aspects in private dental practice

The aim of this research was to evaluate the knowledge of cross-infection hazards in private dental practices, and their control procedures. The survey, carried out by questionnaire in 11 Italian cities, showed that dental personnel do not completely follow the main procedures for infection control. The interviewed subjects usually wear gloves (95.5%), masks (90.1%) and glasses (91.2%), less frequently caps (23.9%) and coats (54.9%). They use steam sterilizers (92.9%) and periodically check the effectiveness (80.6%). Regarding individuals protection, 20.5% is not vaccinated against HBV and only 55.2% of those previously vaccinated has checked their immunity. Moreover, the majority of subjects underestimate the infection hazards especially for air-transmitted diseases.     

Ampicillin,gentamicin and teicoplanin as antimicrobial therapy for recurrent Streptococcus agalactiae and Enterococcus faecalis endocarditis in an intravenous drug abuser with HIV infection

Infective endocarditis associated with human immunodeficiency virus (HIV) infection occurs almost exclusively in intravenous (i.v.) drug users and usually involves the tricuspid valve, with an increased mortality rate among patients with a severe degree of immunosuppression. The first reported case of recurrent tricuspid endocarditis sustained by Streptococcus agalactiae and Enterococcus faecalis in an i.v. drug addict during HIV infection is presented. Antimicrobial therapy with i.v. ampicillin, gentamicin and teicoplanin led to complete clinical and echocardiographical recovery.     

Comparison of the plasma pharmacokinetics of lamivudine during twice and once daily administration in patients with HIV

OBJECTIVE: To compare the plasma pharmacokinetics of lamivudine 150mg twice daily and 300mg once daily in patients with HIV-1 infection. DESIGN: Nonblind, sequential, pharmacokinetic study. PARTICIPANTS: 13 patients with HIV-1 infection (median age 36 years). METHODS: Patients were tested during twice daily and then once daily regimens of lamivudine. In both regimens, the total daily dose of lamivudine was identical (300 mg/day). Blood samples for pharmacokinetic analysis were taken over a 12-hour period after > or =7 days of twice daily administration, and again over a 24-hour period after 7 days of once daily administration,. RESULTS: 12 patients completed the study. Lamivudine pharmacokinetic parameters (mean +/- SD) after administration of 150mg twice daily were: peak plasma concentration (Cmax) 2077+/-816 microg/L; trough plasma concentration (Cmin) 332+/-219 microg/L; elimination half-life (t 1/2beta) 6.1+/-1.9h; time to Cmax (t(max)) 1.6+/-0.7h; average concentration over the dosage interval (Cav) 711+/-269 microg/L; and area under the concentration-time curve (AUC) over 2 dosage intervals (24h) 17085+/-6464 microg x h/L. Corresponding values after administration of 300mg once daily were: Cmax 3461+/-854 microg/L; Cmin 146+/-87 microg/L; t1/2 7.9+/-3.4h; t(max) 2.2+/-1.3h; Cav 705+/-177 microg/L; and AUC over 1 dosage interval (24h) 16644+/-4150 microg x h/L. Statistical analysis showed a significant difference (p < 0.05) between the 2 schedules for Cmax and Cmin values, whereas no significant differences emerged for the other parameters. CONCLUSIONS: Once daily lamivudine leads to a similar exposure in plasma as twice daily administration of the same total daily dose. Since once daily administration may result in improved compliance, these results provide the pharmacokinetic basis for using lamivudine in a once daily regimen. Randomised clinical studies are needed to confirm this pharmacokinetic finding.     

Somatostatin up-regulates topoisomerase II alpha expression and affects LNCaP cell cycle

mRNA differential display-PCR analysis was used to perform a systematic screening of Somatostatin (SS)-regulated genes in the human prostatic carcinoma cell line LNCaP (Lymph Node Carcinoma of the Prostate). A 170 bp fragment was shown to be up-regulated by SS. Sequence analysis of this fragment revealed its homology with the human Topoisomerase II Alpha gene. Up-regulation of Topoisomerase II Alpha was confirmed by Northern blot hybridisation and was induced by the same dose of SS (1 nM) earlier demonstrated to inhibit LNCaP cell growth. Furthermore, SS possible effects on timing, as well as concentration of Topoisomerase II Alpha along the different phases of the cell cycle were investigated. To this purpose changes in the enzyme protein concentration in response to SS were assessed in synchronised LNCaP cells. The hormone was shown to exert a perturbing effect on both parameters considered, possibly related to its inhibitory action on LNCaP cell replication.