DEXA analysis of Antega total hip prosthesis

Periprosthetic bone remodeling can be studied using dual-energy absorptiometry X-ray analysis (DEXA), the most precise and effective method for analyzing bone mineral density (BMD). However, in order to show significant differences in BMD using DEXA, it is necessary to use high resolution equipment, to demonstrate reproducibility of the examination, and to adopt statistical rigor in data analysis. We performed a longitudinal study using DEXA on a consecutive and homogeneous series of 40 patients (20 males and 20 females) who underwent total hip replacement. The patients received a cementless Antega prosthesis, of titanium alloy with a plasma spray covering. DEXA exams were performed 1, 4, 7, 12 and 24 months after surgery, and the images were analyzed in the areas of Gruen. Globally, BMD was significantly reduced at month 4 in reference to baseline (exam at month 1). At subsequent exams, BMD did not further decrease but was followed by a progressive recovery over the 2-year study. The recovery at 2 years (with respect to the 4-month exam) was statistically significant for female patients but not for males. No statistical differences in BMD were found between patients (60 years and > 60 years, nor for patients with different sized stems. For the individual zones of Gruen, the mineralometric behaviors for zones 2, 3, 5 and 6 were similar while that for zones 1 and 7 showed a particular behavior. The trend in variations of periprosthetic BMD observed in our population differs from that in the majority of studies published in the literature. Our longitudinal densitometric study has all the requisites to be considered reliable; a longer follow-up will strengthen our results which, already in the short term, are valid and support the use of the Antega stem in hip replacement surgery. Received: 14 January 2000/Accepted: 18 February 2000     

The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples

In this review, we first examine the contextual background of structure–pharmacokinetic relationships. Some concepts in drug disposition are briefly recalled, and inherent difficulties instructure–pharmacokinetic relationships are outlined. Lipophilicity is then investigated in the light of the intermolecular and intramolecular interactions it encodes. In the main body of the review, a number of pharmacokinetic processes are examined for their relations with lipophilicity. These processes are taken in a logical sequence of permeation, absorption (intestine, skin, cornea, brain), plasma protein binding, tissue distribution, volume of distribution and renal clearance. Relations between metabolism and lipophilicity are more complex, since biotransformation involves both low-energy (enzyme binding) and high-energy (catalysis) processes. Only the former may be related to lipophilicity. The conclusion argues against faulty statistics and over-interpretation. This revised version was published online in August 2006 with corrections to the Cover Date.     

Management of Dietary Habits and Diarrhea in Fap Individuals: A Mediterranean Low-Inflammatory Dietary Intervention

Background: A total colectomy and a frequent life-long endoscopic surveillance are guaranteed to patients with Familial Adenomatous Polyposis (FAP) to reduce their risk of duodenal and rectal stump cancers. However, after surgery, individuals with FAP suffer from an increased number of diarrheal discharges that force them to dietary restrictions. A non-randomized pilot study was conducted to assess whether a three-month low-inflammatory Mediterranean dietary intervention reduces gastro-intestinal markers of inflammation in FAP individuals. The aim of the present work is to evaluate the participant’s adherence to the proposed dietary recommendations and the change in their number of diarrheal discharges. Methods: 26 FAP individuals aged >18 years, who underwent a total colectomy with ileo-rectal anastomosis and were involved in the surveillance program at the Fondazione IRCCS Istituto Nazionale Tumori of Milan, were included in the present analysis. Results: FAP individuals significantly reduced the Not recommended foods (p-value: 0.002) and increased the consumption of the Recommended ones (p-value: 0.075). The adherence to the proposed dietary recommendations was accompanied by a significant decrease in the number of diarrheal discharges (p-value: 0.008). Conclusions: This study suggests that adhering to a low-inflammatory Mediterranean diet has a potential protective effect on the number of diarrheal discharges in FAP individuals.     

Mycobacterium tuberculosisexploits the CD95/CD95 ligand system of γ δ T cells to cause apoptosis

Vγ9/Vδ2⁺ T cells specifically recognize Mycobacterium tuberculosis in vitro and are precociously recruited in early mycobacterial lesions. Even if γ δ T cells are only fortuitously detected in granulomas or bronchoalveolar lavages of patients with active pulmonary tuberculosis, a role in shaping the mature α β T cell response against M. tuberculosis is substantiated. Here we provide a molecular explanation for this paradox: the engagement of the γ δ TCR by mycobacterial antigens induced the expression of CD95 ligand (CD95L) by chronically activated CD95⁺ /CD95L⁻ γ δ T lymphocytes. The receptor was functional, as CD95/CD95L interaction triggered the bystander death of CD95⁺ cells by apoptosis. Cell death was abolished by CD95-blocking antibodies. The transient accumulation at the site of infection of CD95L⁺ γ δ lymphocytes, capable of interacting with CD95⁺ leukocytes attracted by the response towards the pathogen, may determine the characteristics of the ensuing granulomatous disease.     

Effect of steroid receptors,pS2 and cathepsin D on the outcome of elderly breast cancer patients: An exploratory investigation

In 83 elderly breast cancer patients, oestrogen and progesterone receptors (ER, PgR), pS2 and cathepsin D (CathD) were evaluated for their possible prognostic role on disease-free survival (DFS). The biomarkers were determined on the same cytosol by using immunoradiometric assays, and the variables were considered on a continuous scale. Univariate analysis indicated a linear relationship between logarithmic hazard ratio (log(HR)) and the log(ER) and log(PgR) concentration, but a non-linear relationship between log(HR) and CathD. As regards pS2, there was no evidence of a relationship with log(HR). In multivariate analysis, log(ER) content did not have a significant prognostic role, whereas log(PgR) retained a significant prognostic role. As regards the predictive ability, log(PgR) was the best discriminator of outcome followed by CathD, whereas the contribution of log(ER) was negligible. In multivariate analysis, 2 models were considered: one with log(ER), pS2, CathD and the interaction between pS2 and CathD, and another with log(PgR), pS2, CathD and the interaction between pS2 and CathD. In the first model, log(ER) content did not have a significant prognostic role, whereas in the second model log(PgR) retained a significant prognostic role. Our findings indicate that the quantitative determination of pS2 and CathD, in addition to steroid receptors, on the same cytosolic fraction could be a complementary tool to describe all breast cancer patients rather than just the elderly and that the use of a continuous scale, instead of a simple dichotomous “status”, may improve the biological information supplied by the variables. Int. J. Cancer (Pred. Oncol.) 79:305–311, 1998. © 1998 Wiley-Liss, Inc.